Search results for: tumor inhibition

Authors: Mounir Baccar, Imen Jmal

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Because of the rise in energy costs, thermal storage systems designed for the heating and cooling of buildings are becoming increasingly important. Energy storage can not only reduce the time or rate mismatch between energy supply and demand but also plays an important role in energy conservation. One of the most preferable storage techniques is the Latent Heat Thermal Energy Storage (LHTES) by Phase Change Materials (PCM) due to its important energy storage density and isothermal storage process. This paper presents a numerical study of the solidification of a PCM (paraffin RT27) in a rectangular thermal storage exchanger for air conditioning systems taking into account the presence of natural convection. Resolution of continuity, momentum and thermal energy equations are treated by the finite volume method. The main objective of this numerical approach is to study the effect of natural convection on the PCM solidification time and the impact of fins number on heat transfer enhancement. It also aims at investigating the temporal evolution of PCM solidification, as well as the longitudinal profiles of the HTF circling in the duct. The present research undertakes the study of two cases: the first one treats the solidification of PCM in a PCM-air heat exchanger without fins, while the second focuses on the solidification of PCM in a heat exchanger of the same type with the addition of fins (3 fins, 5 fins, and 9 fins). Without fins, the stratification of the PCM from colder to hotter during the heat transfer process has been noted. This behavior prevents the formation of thermo-convective cells in PCM area and then makes transferring almost conductive. In the presence of fins, energy extraction from PCM to airflow occurs at a faster rate, which contributes to the reduction of the discharging time and the increase of the outlet air temperature (HTF). However, for a great number of fins (9 fins), the enhancement of the solidification process is not significant because of the effect of confinement of PCM liquid spaces for the development of thermo-convective flow. Hence, it can be concluded that the effect of natural convection is not very significant for a high number of fins. In the optimum case, using 3 fins, the increasing temperature of the HTF exceeds approximately 10°C during the first 30 minutes. When solidification progresses from the surfaces of the PCM-container and propagates to the central liquid phase, an insulating layer will be created in the vicinity of the container surfaces and the fins, causing a low heat exchange rate between PCM and air. As the solid PCM layer gets thicker, a progressive regression of the field of movements is induced in the liquid phase, thus leading to the inhibition of heat extraction process. After about 2 hours, 68% of the PCM became solid, and heat transfer was almost dominated by conduction mechanism.

Keywords: heat transfer enhancement, front solidification, PCM, natural convection

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Authors: Xi Chen, King-Yip Cheng

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Hypercholesterolemia, characterized by high low-density lipoprotein cholesterol (LDL-C), raises cardiovascular events in patients with type 2 diabetes (T2D). Although several drugs, such as statin and PCSK9 inhibitors, are available for the treatment of hypercholesterolemia, they exert detrimental effects on glucose metabolism and hence increase the risk of T2D. On the other hand, the drugs used to treat T2D have minimal effect on improving the lipid profile. Therefore, there is an urgent need to develop treatments that can simultaneously improve glucose and lipid homeostasis. Adaptor protein phosphotyrosine interacting with PH domain and leucine zipper 2 (APPL2) causes insulin resistance in the liver and skeletal muscle via inhibiting insulin and adiponectin actions in animal models. Single-nucleotide polymorphisms in the APPL2 gene were associated with LDL-C, non-alcoholic fatty liver disease, and coronary artery disease in humans. The aim of this project is to investigate whether APPL2 antisense oligonucleotide (ASO) can alleviate dietary-induced T2D and hypercholesterolemia. High-fat diet (HFD) was used to induce obesity and insulin resistance in mice. GalNAc-conjugated APPL2 ASO (GalNAc-APPL2-ASO) was used to silence hepatic APPL2 expression in C57/BL6J mice selectively. Glucose, lipid, and energy metabolism were monitored. Immunoblotting and quantitative PCR analysis showed that GalNAc-APPL2-ASO treatment selectively reduced APPL2 expression in the liver instead of other tissues, like adipose tissues, kidneys, muscle, and heart. The glucose tolerance test and insulin sensitivity test revealed that GalNAc-APPL2-ASO improved glucose tolerance and insulin sensitivity progressively. Blood chemistry analysis revealed that the mice treated with GalNAc-APPL2-ASO had significantly lower circulating levels of total cholesterol and LDL cholesterol. However, there was no difference in circulating levels of high-density lipoprotein (HDL) cholesterol, triglyceride, and free fatty acid between the mice treated with GalNac-APPL2-ASO and GalNAc-Control-ASO. No obvious effect on food intake, body weight, and liver injury markers after GalNAc-APPL2-ASO treatment was found, supporting its tolerability and safety. We showed that selectively silencing hepatic APPL2 alleviated insulin resistance and hypercholesterolemia and improved energy metabolism in the dietary-induced obese mouse model, indicating APPL2 as a therapeutic target for metabolic diseases.

Keywords: APPL2, antisense oligonucleotide, hypercholesterolemia, type 2 diabetes

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Authors: B. Grygalewicz, R. Woroniecka, J. Rygier, K. Borkowska, A. Labak, B. Nowakowska, B. Pienkowska-Grela

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Introduction: Chronic lymphocytic leukemia (CLL) is the most common form of adult leukemia in the Western world. Hemizygous and or homozygous loss at 13q14 occur in more than half of cases and constitute the most frequent chromosomal abnormality in CLL. It is believed that deletions 13q14 play a role in CLL pathogenesis. Two microRNA genes miR-15a and miR- 16-1 are targets of 13q14 deletions and plays a tumor suppressor role by targeting antiapoptotic BCL2 gene. Deletion size, as a single change detected in FISH analysis, has haprognostic significance. Patients with small deletions, without RB1 gene involvement, have the best prognosis and the longest overall survival time (OS 133 months). In patients with bigger deletion region, containing RB1 gene, prognosis drops to intermediate, like in patients with normal karyotype and without changes in FISH with overall survival 111 months. Aim: Precise delineation of 13q14 deletions regions in two groups of CLL patients, with mono- and biallelic deletions and qualifications of their prognostic significance. Methods: Detection of 13q14 deletions was performed by FISH analysis with CLL probe panel (D13S319, LAMP1, TP53, ATM, CEP-12). Accurate deletion size detection was performed by CGH Haematological Cancer and SNP array (8x60K). Results: Our investigated group of CLL patients with the 13q14 deletion, detected by FISH analysis, comprised two groups: 18 patients with monoallelic deletions and 18 patients with biallelic deletions. In FISH analysis, in the monoallelic group the range of cells with deletion, was 43% to 97%, while in biallelic group deletion was detected in 11% to 94% of cells. Microarray analysis revealed precise deletion regions. In the monoallelic group, the range of size was 348,12 Kb to 34,82 Mb, with median deletion size 7,93 Mb. In biallelic group discrepancy of total deletions, size was 135,27 Kb to 33,33 Mb, with median deletion size 2,52 Mb. The median size of smaller deletion regions on one copy chromosome 13 was 1,08 Mb while the average region of bigger deletion on the second chromosome 13 was 4,04 Mb. In the monoallelic group, in 8/18 deletion region covered RB1 gene. In the biallelic group, in 4/18 cases, revealed deletion on one copy of biallelic deletion and in 2/18 showed deletion of RB1 gene on both deleted 13q14 regions. All minimal deleted regions included miR-15a and miR-16-1 genes. Genetic results will be correlated with clinical data. Conclusions: Application of CGH microarrays technique in CLL allows accurately delineate the size of 13q14 deletion regions, what have a prognostic value. All deleted regions included miR15a and miR-16-1, what confirms the essential role of these genes in CLL pathogenesis. In our investigated groups of CLL patients with mono- and biallelic 13q14 deletions, patients with biallelic deletion presented smaller deletion sizes (2,52 Mb vs 7,93 Mb), what is connected with better prognosis.

Keywords: CLL, deletion 13q14, CGH microarrays, SNP array

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Authors: Hana Al-Baghaoi, Kumar Shiva Gubbiyappa, Mayuren Candasamy, Kiruthiga Perumal Vijayaraman

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Acne is a chronic inflammatory disease of the sebaceous glands characterized by areas of skin with seborrhea, comedones, papules, pustules, nodules, and possibly scarring. Propionibacterium acnes (P. acnes), plays a key role in the pathogenesis of acne. Their colonization and proliferation trigger the host’s inflammatory response leading to the production of pro-inflammatory cytokines such as interleukin-8 (IL-8) and tumour necrosis factor-α (TNF-α). The usage of honey and natural compounds to treat skin ailments has strong support in the current trend of drug discovery. The present study was carried out evaluate antimicrobial and anti-inflammatory potential of Doani Sidr honey and its fractions against P. acnes and to screen madecassoside alone and in combination with fractions of honey. The broth dilution method was used to assess the antibacterial activity. Also, ultra structural changes in cell morphology were studied before and after exposure to Sidr honey using transmission electron microscopy (TEM). The three non-toxic concentrations of the samples were investigated for suppression of cytokines IL 8 and TNF α by testing the cell supernatants in the co-culture of the human peripheral blood mononuclear cells (hPBMCs) heat killed P. acnes using enzyme immunoassay kits (ELISA). Results obtained was evaluated by statistical analysis using Graph Pad Prism 5 software. The Doani Sidr honey and polysaccharide fractions were able to inhibit the growth of P. acnes with a noteworthy minimum inhibitory concentration (MIC) value of 18% (w/v) and 29% (w/v), respectively. The proximity of MIC and MBC values indicates that Doani Sidr honey had bactericidal effect against P. acnes which is confirmed by TEM analysis. TEM images of P. acnes after treatment with Doani Sidr honey showed completely physical membrane damage and lysis of cells; whereas non honey treated cells (control) did not show any damage. In addition, Doani Sidr honey and its fractions significantly inhibited (> 90%) of secretion of pro-inflammatory cytokines like TNF α and IL 8 by hPBMCs pretreated with heat-killed P. acnes. However, no significant inhibition was detected for madecassoside at its highest concentration tested. Our results suggested that Doani Sidr honey possesses both antimicrobial and anti-inflammatory effects against P. acnes and can possibly be used as therapeutic agents for acne. Furthermore, polysaccharide fraction derived from Doani Sidr honey showed potent inhibitory effect toward P. acnes. Hence, we hypothesize that fraction prepared from Sidr honey might be contributing to the antimicrobial and anti-inflammatory activity. Therefore, this polysaccharide fraction of Doani Sidr honey needs to be further explored and characterized for various phytochemicals which are contributing to antimicrobial and anti-inflammatory properties.

Keywords: Doani sidr honey, Propionibacterium acnes, IL-8, TNF alpha

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Authors: Paola Modesto, Floriana Fruscione, Isabella Martini, Simona Perga, Federica Riccardo, Mariateresa Camerino, Davide Giacobino, Cecilia Gola, Luca Licenziato, Elisabetta Razzuoli, Katia Varello, Lorella Maniscalco, Elena Bozzetta, Angelo Ferrari

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Canine and human melanoma, osteosarcoma (OSA), and mammary carcinomas are aggressive tumors with common characteristics making dogs a good model for comparative oncology. Novel therapeutic strategies against these tumors could be useful to both species. In humans, chondroitin sulphate proteoglycan 4 (CSPG4) is a marker involved in tumor progression and could be a candidate target for immunotherapy. The anti-CSPG4 DNA electrovaccination has shown to be an effective approach for canine malignant melanoma (CMM) [1]. An immunohistochemistry evaluation of CSPG4 expression in tumour tissue is generally performed prior to electrovaccination. To assess the possibility to perform a rapid molecular evaluation and in order to validate these spontaneous canine tumors as the model for human studies, we investigate the CSPG4 gene expression by RT qPCR in CMM, OSA, and canine mammary tumors (CMT). The total RNA was extracted from RNAlater stored tissue samples (CMM n=16; OSA n=13; CMT n=6; five paired normal tissues for CMM, five paired normal tissues for OSA and one paired normal tissue for CMT), retro-transcribed and then analyzed by duplex RT-qPCR using two different TaqMan assays for the target gene CSPG4 and the internal reference gene (RG) Ribosomal Protein S19 (RPS19). RPS19 was selected from a panel of 9 candidate RGs, according to NormFinder analysis following the protocol already described [2]. Relative expression was analyzed by CFX Maestro™ Software. Student t-test and ANOVA were performed (significance set at P<0.05). Results showed that gene expression of CSPG4 in OSA tissues is significantly increased by 3-4 folds when compared to controls. In CMT, gene expression of the target was increased from 1.5 to 19.9 folds. In melanoma, although an increasing trend was observed, no significant differences between the two groups were highlighted. Immunohistochemistry analysis of the two cancer types showed that the expression of CSPG4 within CMM is concentrated in isles of cells compared to OSA, where the distribution of positive cells is homogeneous. This evidence could explain the differences in gene expression results.CSPG4 immunohistochemistry evaluation in mammary carcinoma is in progress. The evidence of CSPG4 expression in a different type of canine tumors opens the way to the possibility of extending the CSPG4 immunotherapy marker in CMM, OSA, and CMT and may have an impact to translate this strategy modality to human oncology.

Keywords: canine melanoma, canine mammary carcinomas, canine osteosarcoma, CSPG4, gene expression, immunotherapy

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Authors: Benjamin Castillo, Luis Pastenes, Fernando Cerdova

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The contamination of food by microbial agents is a common problem in the industry, especially regarding the elaboration of animal source products. Incorrect manipulation of the machinery or on the raw materials can cause a decrease in production or an epidemiological outbreak due to intoxication. In order to improve food product quality, different methods have been used to reduce or, at least, to slow down the growth of the pathogens, especially deteriorated, infectious or toxigenic bacteria. These methods are usually carried out under low temperatures and short processing time (abiotic agents), along with the application of antibacterial substances, such as bacteriocins (biotic agents). This, in a controlled and efficient way that fulfills the purpose of bacterial control without damaging the final product. Therefore, the objective of the present study is to design a secondary mathematical model that allows the prediction of both the biotic and abiotic factor impact associated with animal source food processing. In order to accomplish this objective, the authors propose a three-dimensional differential equation model, whose components are: bacterial growth, release, production and artificial incorporation of bacteriocins and changes in pH levels of the medium. These three dimensions are constantly being influenced by the temperature of the medium. Secondly, this model adapts to an idealized situation of cross-contamination animal source food processing, with the study agents being both the animal product and the contact surface. Thirdly, the stochastic simulations and the parametric sensibility analysis are compared with referential data. The main results obtained from the analysis and simulations of the mathematical model were to discover that, although bacterial growth can be stopped in lower temperatures, even lower ones are needed to eradicate it. However, this can be not only expensive, but counterproductive as well in terms of the quality of the raw materials and, on the other hand, higher temperatures accelerate bacterial growth. In other aspects, the use and efficiency of bacteriocins are an effective alternative in the short and medium terms. Moreover, an indicator of bacterial growth is a low-level pH, since lots of deteriorating bacteria are lactic acids. Lastly, the processing times are a secondary agent of concern when the rest of the aforementioned agents are under control. Our main conclusion is that when acclimating a mathematical model within the context of the industrial process, it can generate new tools that predict bacterial contamination, the impact of bacterial inhibition, and processing method times. In addition, the mathematical modeling proposed logistic input of broad application, which can be replicated on non-meat food products, other pathogens or even on contamination by crossed contact of allergen foods.

Keywords: bacteriocins, cross-contamination, mathematical model, temperature

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Authors: Rajish Shil, Amal Alduhoori, Vipin Thomachan, Jamal Teir, Radhakrishnan Renganathan

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Background: Antiphospholipid antibody syndrome (APS) has a broad spectrum of thrombotic and non-thrombotic clinical manifestations. We present a case of APS presenting with seizure, stroke, and atrial mass. Case Description: A 38-year-old male presented with headache of 10 days duration and tonic-clonic seizure. The neurological examination was normal. Magnetic resonance imaging of brain showed small acute right cerebellar infarct. Magnetic resonance angiography of brain and neck showed a focal narrowing in the origin of the internal carotid artery bilaterally. Electroencephalogram was normal. He was started on aspirin, atorvastatin, and carbamazepine. Transthoracic and trans-esophageal echocardiography showed a pedunculated and lobular atrial mass, measuring 1 X 1.5 cm, which was freely mobile across mitral valve opening across the left ventricular inflow. Autoimmune screening showed positive Antiphospholipid antibodies in high titer (Cardiolipin IgG > 120 units/ml, B2 glycoprotein IgG 90 units/mL). Anti-nuclear antibody was negative. Erythrocyte sedimentation rate and C-reactive protein levels were normal. Platelet count was low (111 x 109/L). The patient underwent successful surgical removal of the mass, which looked like a thrombotic clot, and Histopathological analysis confirmed it as a fibrinous clot, with no evidence of tumor cells. The patient was started on full anticoagulation treatment and was followed up regularly in the clinic, where our patient did not have any further complications from the disease. Discussion: Our patient was diagnosed to have APS based on the features of high positive anticardiolipin antibody IgG and B2 glycoprotein IgG levels, Stroke, thrombocytopenia, and abnormal echo findings. Thrombotic vegetation can mimic an atrial myxoma on echo. Conclusion: APS can present with neurological and cardiac manifestations, and therefore a high index of suspicion is necessary for a diagnosis of the disease as it can affect both short and long term treatment plans and prognosis. Therefore, in patients presenting with neurological symptoms like seizures, weakness and radiological diagnosis of stroke in a young patient, where atrial masses could be thought to be the cause of stroke, they should be screened for any concomitant findings of thrombocytopenia and/or activated partial thromboplastin time prolongation, which should raise the suspicion of vasculitis, specifically APS to be the primary cause of the clinical presentation.

Keywords: antiphospholipid syndrome, seizures, atrial mass, stroke

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Authors: G. V. Manzane, S. J. Modise

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Uterine fibroids, also known as leiomyomas or myomas, are non-cancerous growths that develop in the muscular wall of the uterus during the reproductive years. The cause of uterine fibroids includes hormonal, genetic, growth factors, and extracellular matrix factors. Common symptoms of uterine fibroids include heavy and prolonged menstrual bleeding which can lead to a high risk of anemia, lower abdominal pains, pelvic pressure, infertility, and pregnancy loss. The growth of this tumor is a concern because of its negative impact on women’s health and the increase in their economic burden. Traditional medicinal plants have long been used in Africa for their potential therapeutic effects against various ailments. In this study, we aimed to identify and characterize bioactive compounds from selected African medicinal plants with potential anti-fibrotic properties using Fourier-transform infrared spectroscopy (FTIR) and gas chromatography-mass spectrometry (GCMS) analysis. Two medicinal plant species known for their traditional use in fibrosis-related conditions were selected for investigation. Aqueous extracts were prepared from the plant materials, and FTIR analysis was conducted to determine the functional groups present in the extracts. GCMS analysis was performed to identify the chemical constituents of the extracts. The FTIR analysis revealed the presence of various functional groups, such as phenols, flavonoids, terpenoids, and alkaloids, known for their potential therapeutic activities. These functional groups are associated with antioxidant, anti-inflammatory, and anti-fibrotic properties. The GCMS analysis identified several bioactive compounds, including flavonoids, alkaloids, terpenoids, and phenolic compounds, which are known for their pharmacological activities. The discovery of bioactive compounds in African medicinal plants that exhibit anti-fibrotic effects, opens up promising avenues for further research and development of potential treatments for fibrosis. This suggests the potential of these plants as a valuable source of novel therapeutic agents for treating fibrosis-related conditions. In conclusion, our study identified and characterized bioactive compounds from selected African medicinal plants using FTIR and GCMS analysis. The presence of compounds with known antifibrotic properties suggests that these plants hold promise as a potential source of natural products for the development of novel anti-fibrotic therapies.

Keywords: uterine fibroids, african medicinal plants, bioactive compounds, identify and characterized

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Authors: Showkat Ahmad Bhat, Iqra Reyaz, Falaque ul Afshan, Ahmad Arif Reshi, Muneeb U. Rehman, Manzoor R. Mir, Sabhiya Majid, Sonallah, Sheikh Bilal, Ishraq Hussain

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Background: Gastric cancer is the fourth most common cancer and the second leading cause of worldwide cancer-related deaths, with a wide variation in incidence rates across different geographical areas. The current view of cancer is that a malignancy arises from a transformation of the genetic material of a normal cell, followed by successive mutations and by chain of alterations in genes such as DNA repair genes, oncogenes, Tumor suppressor genes. Minerals are necessary for the functioning of several transcriptional factors, proteins that recognize certain DNA sequences and have been found to play a role in gastric cancer. Material Methods:The present work was a case control study and its aim was to ascertain the role of minerals and promoter hypermethylation of CpG islands of DAP-K gene in Gastric cancer patients among the Kashmiri population. Serum was extracted from all the samples and mineral estimation was done by AAS from serum, DNA was also extracted and was modified using bisulphite modification kit. Methylation-specific PCR was used for the analysis of the promoter hypermethylation status of DAP-K gene. The epigenetic analysis revealed that unlike other high risk regions, Kashmiri population has a different promoter hypermethylation profile of DAP-K gene and has different mineral profile. Results: In our study mean serum copper levels were significantly different for the two genders (p<0.05), while as no significant differences were observed for iron and zinc levels. In Methylation-specific PCR the methylation status of the promoter region of DAP-K gene was as 67.50% (27/40) of the gastric cancer tissues showed methylated DAP-K promoter and 32.50% (13/40) of the cases however showed unmethylated DAP-K promoter. Almost all 85% (17/20) of the histopathologically confirmed normal tissues showed unmethylated DAP-K promoter except only in 3 cases where DAP-K promoter was found to be methylated. The association of promoter hypermethylation with gastric cancer was evaluated by χ2 (Chi square) test and was found to be significant (P=0.0006). Occurrence of DAP-K methylation was found to be unequally distributed in males and females with more frequency in males than in females but the difference was not statistically significant (P =0.7635, Odds ratio=1.368 and 95% C.I=0.4197 to 4.456). When the frequency of DAP-K promoter methylation was compared with clinical staging of the disease, DAP-K promoter methylation was found to be certainly higher in Stage III/IV (85.71%) compared to Stage I/ II (57.69%) but the difference was not statistically significant (P =0.0673). These results suggest that DAP-K aberrant promoter hypermethylation in Kashmiri population contributes to the process of carcinogenesis in Gastric cancer and is reportedly one of the commonest epigenetic changes in the development of Gastric cancer.

Keywords: gastric cancer, minerals, AAS, hypermethylation, CpG islands, DAP-K gene

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Authors: Shashi Bala, Neha A. Chugh, Subhash C. Bansal, Mohal L. Garg, Ashwani Koul

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Purpose: The present study was designed to evaluate the radioprotective efficacy of Aloe vera from whole body X-ray exposure in rodents. Materials and Methods: For this purpose, after on week’s acclimatization, male balb/c mice procured from Central Animal House, Panjab University, Chandigarh (India), were divided into four groups: Group I mice served as control. Group II mice were orally administrated Aloe vera pulp extract (50 mg/ kg body weight) on alternate days for 30 days. Group III mice were subjected to whole body X-ray irradiation to cumulative dose of 2Gy (0.258Gy twice a day for four days in the last week). Group IV animals were pretreated with Aloe vera pulp extract on alternate days as in Group II and in the last week of the study, they were exposed to X-ray as in Group III. Results: Spleen of X-ray irradiated mice showed histopathological alterations accompanied with enhanced activity of lactate dehydrogenase (LDH) in serum. Elevated levels of reactive oxygen species (ROS), lipid peroxidation (LPO), enhanced activities in Glutathione based enzymes such as Glutathione peroxidase (GSH-Px), Glutathione reductase (GR), Catalase (CAT), Superoxide dismutase (SOD) associated with depletion in reduced Glutathione (GSH) concentration were observed after X-ray exposure in blood plasma and spleen.. Pro-inflammatory cytokines like tumor necrosis factors (TNF-α) and Inteleukin-6 (IL-6) levels were also found to be enhanced in serum of irradiated mice. Irradiation-induced significant elevation in Total leucocyte counts (TLC), neutrophil counts and decline in platelet counts, associated with unaltered levels of red blood cell counts (RBC’s) and haemoglobin (Hb) in various treatment groups. Clastogenic damage and apoptosis was also found to be increase in splenic tissue of X-ray exposed mice as assessed by micronucleus and TUNEL assay. However, X-ray irradiated animals administered with Aloe vera revealed significant improvement in levels of ROS/ LPO, LDH activity, and antioxidant mechanism. Aloe vera pretreated animals exhibited less severe damage, and early recovery in micronucleated cells, hematological parameters, apoptotic cells and inflammatory markers as compared to X-ray exposed mice. Conclusion: These results indicate that the radioprotective potential of Aloe vera against X-ray induced damage. This may be due to its free radical scavenging, antioxidant, anti-apoptotic and anti-inflammatory properties.

Keywords: aloe vera, antioxidant defense system, lactate dehydrogenase (LDH), micronucleus assay, x-ray

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Authors: Jeongyeon Park, Yeo Jun Yoon, Jiyoung Seo, In Seok Moon, Hae Jun Lee, Kiwon Song

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Cold Atmospheric Pressure Plasma (CAPP) is defined as a partially ionized gas with electrically charged particles at room temperature and atmospheric pressure. CAPP generates reactive oxygen species (ROS) and reactive nitrogen species (RNS), and has potential as a new apoptosis-promoting cancer therapy. With an annular type dielectric barrier discharge (DBD) CAPP-generating device combined with a helium (He) gas feeding system, we showed that CAPP selectively induced apoptosis in various cancer cells while it promoted proliferation of the adipose tissue-derived stem cell (ASC). The apoptotic effect of CAPP was highly selective toward p53-mutated cancer cells. The intracellular ROS was mainly responsible for apoptotic cell death in CAPP-treated cancer cells. CAPP induced apoptosis even in doxorubicin-resistant cancer cell lines, demonstrating the feasibility of CAPP as a potent cancer therapy. With the same device and exposure conditions to cancer cells, CAPP stimulated proliferation of the ASC, a kind of mesenchymal stem cell that is capable of self-renewing and differentiating into adipocytes, chondrocytes, osteoblasts and neurons. CAPP-treated ASCs expressed the stem cell markers and differentiated into adipocytes as untreated ASCs. The increase of proliferation by CAPP in ASCs was offset by a NO scavenger but was not affected by ROS scavengers, suggesting that NO generated by CAPP is responsible for the activated proliferation in ASCs. Usually, cancer stem cells are reported to be resistant to known cancer therapies. When we applied CAPP of the same device and exposure conditions to cancer cells to liver cancer stem cells (CSCs) that express CD133 and epithelial cell adhesion molecule (EpCAM) cancer stem cell markers, apoptotic cell death was not examined. Apoptotic cell death of liver CSCs was induced by the CAPP generated from a device with an air-based flatten type DBD. An exposure of liver CSCs to CAPP decreased the viability of liver CSCs to a great extent, suggesting plasma be used as a promising anti-cancer treatment. To validate whether CAPP can be a promising anti-cancer treatment or an adjuvant modality to eliminate remnant tumor in cancer surgery of vestibular schwannoma, we applied CAPP to mouse schwannoma cell line SC4 Nf2 ‑/‑ and human schwannoma cell line HEI-193. A CAPP treatment leads to anti-proliferative effect in both cell lines. We are currently studying the molecular mechanisms of differential physiological effect of CAPP; the proliferation of ASCs and apoptosis of various cancer cells and CSCs.

Keywords: cold atmospheric pressure plasma, apoptosis, proliferation, cancer cells, adult stem cells

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Authors: Ahmed Abdallatif

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Background: Patients with malignant germ cell tumors have age distribution in two peaks, with the first one during infancy and the second after the onset of puberty. Gonadal germ cell tumors are the most common malignant ovarian tumor in females aged below twenty years. Sacrococcygeal and retroperitoneal abdominal tumors usually presents in a large size before the onset of symptoms. Methods: Patients with pediatric germ cell tumors presenting to Children’s Cancer Hospital Egypt and National Cancer Institute Egypt from January 2008 to June 2011 Patients underwent stratification according to risk into low, intermediate and high risk groups according to children oncology group classification. Objectives: Assessment of the clinicopathologic features of all cases of pediatric germ cell tumors and classification of malignant cases according to their stage, and the primary site to low, intermediate and high risk patients. Evaluation of surgical management in each group of patients focusing on surgical approach, the extent of surgical resection according to each site, ability to achieve complete surgical resection and perioperative complications. Finally, determination of the three years overall and disease-free survival in different groups and the relation to different prognostic factors including the extent of surgical resection. Results: Out of 131 cases surgically explored only 26 cases had re exploration with 8 cases explored for residual disease 9 cases for remote recurrence or metastatic disease and the other 9 cases for other complications. Patients with low risk kept under follow up after surgery, out of those of low risk group (48 patients) only 8 patients (16.5%) shifted to intermediate risk. There were 20 patients (14.6%) diagnosed as intermediate risk received 3 cycles of compressed (Cisplatin, Etoposide and Bleomycin) and all high risk group patients 69patients (50.4%) received chemotherapy. Stage of disease was strongly and significantly related to overall survival with a poorer survival in late stages (stage IV) as compared to earlier stages. Conclusion: Overall survival rate at 3 three years was (76.7% ± 5.4, 3) years EFS was (77.8 % ±4.0), however 3 years DFS was much better (89.8 ± 3.4) in whole study group with ovarian tumors had significantly higher Overall survival (90% ± 5.1). Event Free Survival analysis showed that Male gender was 3 times likely to have bad events than females. Patients who underwent incomplete resection were 4 times more than patients with complete resection to have bad events. Disease free survival analysis showed that Patients who underwent incomplete surgery were 18.8 times liable for recurrence compared to those who underwent complete surgery, and patients who were exposed to re-excision were 21 times more prone to recurrence compared to other patients.

Keywords: extragonadal, germ cell tumors, gonadal, pediatric

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Authors: José Maria, Vânia Laranjo, Luís Abrunhosa, António Inês

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The occurrence of mycotoxigenic moulds such as Aspergillus, Penicillium and Fusarium in food and feed has an important impact on public health, by the appearance of acute and chronic mycotoxicoses in humans and animals, which is more severe in the developing countries due to lack of food security, poverty and malnutrition. This mould contamination also constitutes a major economic problem due the lost of crop production. A great variety of filamentous fungi is able to produce highly toxic secondary metabolites known as mycotoxins. Most of the mycotoxins are carcinogenic, mutagenic, neurotoxic and immunosuppressive, being ochratoxin A (OTA) one of the most important. OTA is toxic to animals and humans, mainly due to its nephrotoxic properties. Several approaches have been developed for decontamination of mycotoxins in foods, such as, prevention of contamination, biodegradation of mycotoxins-containing food and feed with microorganisms or enzymes and inhibition or absorption of mycotoxin content of consumed food into the digestive tract. Some group of Gram-positive bacteria named lactic acid bacteria (LAB) are able to release some molecules that can influence the mould growth, improving the shelf life of many fermented products and reducing health risks due to exposure to mycotoxins. Some LAB are capable of mycotoxin detoxification. Recently our group was the first to describe the ability of LAB strains to biodegrade OTA, more specifically, Pediococcus parvulus strains isolated from Douro wines. The pathway of this biodegradation was identified previously in other microorganisms. OTA can be degraded through the hydrolysis of the amide bond that links the L-β-phenylalanine molecule to the ochratoxin alpha (OTα) a non toxic compound. It is known that some peptidases from different origins can mediate the hydrolysis reaction like, carboxypeptidase A an enzyme from the bovine pancreas, a commercial lipase and several commercial proteases. So, we wanted to have a better understanding of this OTA degradation process when LAB are involved and identify which molecules where present in this process. For achieving our aim we used some bioinformatics tools (BLAST, CLUSTALX2, CLC Sequence Viewer 7, Finch TV). We also designed specific primers and realized gene specific PCR. The template DNA used came from LAB strains samples of our previous work, and other DNA LAB strains isolated from elderberry fruit, silage, milk and sausages. Through the employment of bioinformatics tools it was possible to identify several proteins belonging to the carboxypeptidase family that participate in the process of OTA degradation, such as serine type D-Ala-D-Ala carboxypeptidase and membrane carboxypeptidase. In conclusions, this work has identified carboxypeptidase proteins being one of the molecules present in the OTA degradation process when LAB are involved.

Keywords: carboxypeptidase, lactic acid bacteria, mycotoxins, ochratoxin a.

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Authors: Nicole C. Valdez, Vincent L. Borromeo, Conrad C. Chong, Ahmad F. Mazahery

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Breast cancer is the most prevalent cancer worldwide, where the majority of cases are estrogen-receptor positive and involve 2 receptor proteins. The binding of estrogen to estrogen receptor alpha (ERα) promotes breast cancer growth, while it's binding to estrogen-receptor beta (ERβ) inhibits tumor growth. While natural products have been a promising source of chemotherapeutic agents, the challenge remains in finding a bioactive compound that specifically targets cancer cells, minimizing side effects on normal cells. Flavonoids are natural products that act as phytoestrogens and induce the same response as estrogen. They are able to compete with estrogen for binding to ERα; however, it has a higher binding affinity for ERβ. Their abundance in nature and low toxicity make them a potential candidate for breast cancer treatment. This study aimed to determine which particular flavonoids can specifically recognize ERβ and potentially be used for breast cancer treatment through molecular docking. A total of 206 flavonoids comprised of 97 isoflavones and 109 flavanones were collected from ZINC15, while the 3D structures of ERβ and ERα were obtained from Protein Data Bank. These flavonoid subclasses were chosen as they bind more strongly to ERs due to their chemical structure. The structures of the flavonoid ligands were converted using Open Babel, while the estrogen receptor protein structures were prepared using Autodock MGL Tools. The optimal binding site was found using BIOVIA Discovery Studio Visualizer before docking all flavonoids on both ERβ and ERα through Autodock Vina. Genistein is a flavonoid that exhibits anticancer effects by binding to ERβ, so its binding affinity was used as a baseline. Eriodictyol and 4”,6”-Di-O-Galloylprunin both exceeded genistein’s binding affinity for ERβ and was lower than its binding affinity for ERα. Of the two, eriodictyol was pursued due to its antitumor properties on a lung cancer cell line and on glioma cells. It is able to arrest the cell cycle at the G2/M phase by inhibiting the mTOR/PI3k/Akt cascade and is able to induce apoptosis via the PI3K/Akt/NF-kB pathway. Protein pathway and gene analysis were also conducted using ChEMBL and PANTHER and it was shown that eriodictyol might induce anticancer effects through the ROS1, CA7, KMO, and KDM1A genes which are involved in cell proliferation in breast cancer, non-small cell lung cancer, and other diseases. The high binding affinity of eriodictyol to ERβ, as well as its potential affected genes and antitumor effects, therefore, make it a candidate for the development of new breast cancer treatment. Verification through in vitro experiments such as checking the upregulation and downregulation of genes through qPCR and checking cell cycle arrest using a flow cytometry assay is recommended.

Keywords: breast cancer, estrogen receptor, flavonoid, molecular docking

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Authors: Martyna Chotomska, Aleksandra Studzinska, Marta Lisowska, Justyna Szubert, Aleksandra Tabis, Jacek Bania, Arkadiusz Miazek

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Objectives: Assessing antigen-specific T cell responses is of utmost importance for the pre-clinical testing of prototype vaccines against intracellular pathogens and tumor antigens. Mainly two types of in vitro assays are used for this purpose 1) enzyme-linked immunospot (ELISpot) and 2) intracellular cytokine staining (ICS). Both are time-consuming, relatively expensive, and require manual dexterity. Here, we assess if a straightforward detection of luciferase activity in blood samples of transgenic reporter mice expressing a secreted Lucia luciferase under the transcriptional control of IFN-γ promoter parallels the sensitivity of IFNγ ELISpot assay. Methods: IFN-γ-LUCIA mouse strain carrying multiple copies of Lucia luciferase transgene under the transcriptional control of IFNγ minimal promoter were generated by pronuclear injection of linear DNA. The specificity of transgene expression and mobilization was assessed in vitro using transgenic splenocytes exposed to various mitogens. The IFN-γ-LUCIA mice were immunized with 50mg of ovalbumin (OVA) emulsified in incomplete Freund’s adjuvant three times every two weeks by subcutaneous injections. Blood samples were collected before and five days after each immunization. Luciferase activity was assessed in blood serum. Peripheral blood mononuclear cells were separated and assessed for frequencies of OVA-specific IFNγ-secreting T cells. Results: We show that in vitro cultured splenocytes of IFN-γ-LUCIA mice respond by 2 and 3 fold increase in secreted luciferase activity to T cell mitogens concanavalin A and phorbol myristate acetate, respectively but fail to respond to B cell-stimulating E.coli lipopolysaccharide. Immunization of IFN-γ-LUCIA mice with OVA leads to over 4 fold increase in luciferase activity in blood serum five days post-immunization with a barely detectable increase in OVA-specific, IFNγ-secreting T cells by ELISpot. Second and third immunizations, further increase the luciferase activity and coincidently also increase the frequencies of OVA-specific T cells by ELISpot. Conclusions: We conclude that minimally invasive monitoring of luciferase secretions in blood serum of IFN-γ-LUCIA mice constitutes a sensitive method for evaluating primary and memory Th1 responses to protein antigens. As such, this method may complement existing methods for rapid immunogenicity assessment of prototype vaccines.

Keywords: ELISpot, immunogenicity, interferon-gamma, reporter mice, vaccines

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Authors: Gustavo Axel Elizalde-Velázquez

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Metformin is the first line of oral therapy to treat type II diabetes and is also employed as a treatment for other indications, such as polycystic ovary syndrome, cancer, and COVID-19. Recent data suggest it is the aspirin of the 21st century due to its antioxidant and anti-aging effects. However, increasingly current articles indicate its long-term consumption generates mitochondrial impairment. Up to date, it is known metformin increases the biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, but further information related to brain damage after its consumption is missing. Bearing in mind the above, this work aimed to establish whether or not chronic exposure to metformin may alter swimming behavior and induce neurotoxicity in Danio rerio adults. For this purpose, 250 Danio rerio grown-ups were assigned to six tanks of 50 L of capacity. Four of the six systems contained 50 fish, while the remaining two had 25 fish (≈1 male:1 female ratio). Every system with 50 fish was allocated one of the three metformin treatment concentrations (1, 20, and 40 μg/L), with one system as the control treatment. Systems with 25 fish, on the other hand, were used as positive controls for acetylcholinesterase (10 μg/L of Atrazine) and oxidative stress (3 μg/L of Atrazine). After four months of exposure, a mean of 32 fish (S.D. ± 2) per group of MET treatment survived, which were used for the evaluation of behavior with the Novel Tank test. Moreover, after the behavioral assessment, we aimed to collect the blood and brains of all fish from all treatment groups. For blood collection, fish were anesthetized with an MS-222 solution (150 mg/L), while for brain gathering, fish were euthanized using the hypothermic shock method (2–4 °C). Blood was employed to determine CASP3 activity and the percentage of apoptotic cells with the TUNEL assay, and brains were used to evaluate acetylcholinesterase activity, oxidative damage, and gene expression. After chronic exposure, MET-exposed fish exhibited less swimming activity when compared to control fish. Moreover, compared with the control group, MET significantly inhibited the activity of AChE and induced oxidative damage in the brain of fish. Concerning gene expression, MET significantly upregulated the expression of Nrf1, Nrf2, BAX, p53, BACE1, APP, PSEN1, and downregulated CASP3 and CASP9. Although MET did not overexpress the CASP3 gene, we saw a meaningful rise in the activity of this enzyme in the blood of fish exposed to MET compared to the control group, which we then confirmed by a high number of apoptotic cells in the TUNEL assay. To the best of our understanding, this is the first study that delivers evidence of oxidative impairment, apoptosis, AChE alteration, and overexpression of B- amyloid-related genes in the brain of fish exposed to metformin.

Keywords: AChE inhibition, CASP3 activity, NovelTank test, oxidative damage, TUNEL assay

Procedia PDF Downloads 86

Authors: Sahar Heidary

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Radiography and radiotherapy have emerged as crucial pillars of modern medical practice, revolutionizing diagnostics and treatment for a myriad of health conditions. This abstract highlights the pivotal role of radiography and radiotherapy in favor of healthcare and society. Radiography, a non-invasive imaging technique, has significantly advanced medical diagnostics by enabling the visualization of internal structures and abnormalities within the human body. With the advent of digital radiography, clinicians can obtain high-resolution images promptly, leading to faster diagnoses and informed treatment decisions. Radiography plays a pivotal role in detecting fractures, tumors, infections, and various other conditions, allowing for timely interventions and improved patient outcomes. Moreover, its widespread accessibility and cost-effectiveness make it an indispensable tool in healthcare settings worldwide. On the other hand, radiotherapy, a branch of medical science that utilizes high-energy radiation, has become an integral component of cancer treatment and management. By precisely targeting and damaging cancerous cells, radiotherapy offers a potent strategy to control tumor growth and, in many cases, leads to cancer eradication. Additionally, radiotherapy is often used in combination with surgery and chemotherapy, providing a multifaceted approach to combat cancer comprehensively. The continuous advancements in radiotherapy techniques, such as intensity-modulated radiotherapy and stereotactic radiosurgery, have further improved treatment precision while minimizing damage to surrounding healthy tissues. Furthermore, radiography and radiotherapy have demonstrated their worth beyond oncology. Radiography is instrumental in guiding various medical procedures, including catheter placement, joint injections, and dental evaluations, reducing complications and enhancing procedural accuracy. On the other hand, radiotherapy finds applications in non-cancerous conditions like benign tumors, vascular malformations, and certain neurological disorders, offering therapeutic options for patients who may not benefit from traditional surgical interventions. In conclusion, radiography and radiotherapy stand as indispensable tools in modern medicine, driving transformative improvements in patient care and treatment outcomes. Their ability to diagnose, treat, and manage a wide array of medical conditions underscores their favor in medical practice. As technology continues to advance, radiography and radiotherapy will undoubtedly play an ever more significant role in shaping the future of healthcare, ultimately saving lives and enhancing the quality of life for countless individuals worldwide.

Keywords: radiology, radiotherapy, medical imaging, cancer treatment

Procedia PDF Downloads 69

Authors: Callistus I. Iheme, Kenneth E. Asika, Emmanuel I. Ugwor, Chukwuka U. Ogbonna, Ugonna H. Uzoka, Nneamaka A. Chiegboka, Chinwe S. Alisi, Obinna S. Nwabueze, Amanda U. Ezirim, Judeanthony N. Ogbulie

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Antimicrobial resistance (AMR) is a major threat to the global health sector. Zinc oxide nanocomposites (ZnONCs), composed of zinc oxide nanoparticles and phytochemicals from Azadirachta indica aqueous leaf extract, were assessed for their physico-chemicals, in silico and in vitro antimicrobial properties on multidrug-resistant Escherichia coli enzymes. Gas chromatography coupled with mass spectroscope (GC-MS) analysis on the ZnONCs revealed the presence of twenty volatile phytochemical compounds, among which is scoparone. Characterization of the ZnONCs was done using ultraviolet-visible spectroscopy (UV-vis), energy dispersive spectroscopy (EDX), transmission electron microscopy (TEM), scanning electron microscopy (SEM), and x-ray diffractometer (XRD). Dehydrogenase enzyme converts colorless 2,3,5-triphenyltetrazolium chloride to the red triphenyl formazan (TPF). The rate of formazan formation in the presence of ZnONCs is proportional to the enzyme activities. The color formation is extracted and determined at 500 nm, and the percentage of enzyme activity is calculated. To determine the bioactive components of the ZnONCs, characterize their binding to enzymes, and evaluate the enzyme-ligand complex stability, respectively Discrete Fourier Transform (DFT) analysis, docking, and molecular dynamics simulations will be employed. The results showed arrays of ZnONCs nanorods with maximal absorption wavelengths of 320 nm and 350 nm and thermally stable at the temperature range of 423.77 to 889.69 ℃. In vitro study assessed the dehydrogenase inhibitory properties of the ZnONCs, conjugate of ZnONCs and ampicillin (ZnONCs-amp), the aqueous leaf extract of A. indica, and ampicillin (standard drug). The findings revealed that at the concentration of 500 μm/mL, 57.89 % of the enzyme activities were inhibited by ZnONCs compared to 33.33% and 21.05% of the standard drug (Ampicillin), and the aqueous leaf extract of the A. indica respectively. The inhibition of the enzyme activities by the ZnONCs at 500 μm/mL was further enhanced to 89.74 % by conjugating with Ampicillin. In silico study on the ZnONCs revealed scoparone as the most viable competitor of nicotinamide adenine dinucleotide (NAD⁺) for the coenzyme binding pocket on E. coli malate and histidinol dehydrogenase. From the findings, it can be concluded that the scoparone components of the nanocomposites in synergy with the zinc oxide nanoparticles inhibited E. coli malate and histidinol dehydrogenase by competitively binding to the NAD⁺ pocket and that the conjugation of the ZnONCs with ampicillin further enhanced the antimicrobial efficiency of the nanocomposite against multidrug resistant E. coli.

Keywords: antimicrobial resistance, dehydrogenase activities, E. coli, zinc oxide nanocomposites

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Authors: Belgheis Ebrahimi, Jun Lu

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In recent years, there has been a growing recognition of the potential of marine-based functional foods and combination therapies in promoting a healthy lifestyle and exploring their effectiveness in preventing or treating diseases. The combination of marine bioactive compounds or extracts offers synergistic or enhancement effects through various mechanisms, including multi-target actions, improved bioavailability, enhanced bioactivity, and mitigation of potential adverse effects. Both the green-lipped mussel (GLM) and fucoidan derived from brown seaweed are rich in bioactivities. These two, mussel and fucoidan, have not been previously formulated together. This study aims to combine GLM oil from Perna canaliculus with low molecular weight fucoidan (LMWF) extracted from Undaria pinnatifida to investigate the unique mixture’s anti-inflammatory and antioxidant properties. The cytotoxicity of individual compounds and combinations was assessed using the MTT assay in (THP-1 and RAW264.7) cell lines. The anti-inflammatory activity of mussel-fucoidan was evaluated by treating LPS-stimulated human monocyte and macrophage (THP1-1) cells. Subsequently, the inflammatory cytokines released into the supernatant of these cell lines were quantified via ELISA. Antioxidant activity was determined by using the free radical scavenging assay (DPPH). DPPH assay demonstrated that the radical scavenging activity of the combinations, particularly at concentrations exceeding 1 mg/ml, showed a significantly higher percentage of inhibition when compared to the individual component. This suggests an enhancement effect when the two compounds are combined, leading to increased antioxidant activity. In terms of immunomodulatory activity, the individual compounds exhibited distinct behaviors. GLM oil displayed a higher ability to suppress the cytokine TNF- compared to LMWF. Interestingly, the LMWF fraction, when used individually, did not demonstrate TNF- suppression. However, when combined with GLM, the TNF- suppression (anti-inflammatory) activity of the combination was better than GLM or LWMF alone. This observation underscores the potential for enhancement interactions between the two components in terms of anti-inflammatory properties. This study revealed that each individual compound, LMWF, and GLM, possesses unique and notable bioactivity. The combination of these two individual compounds results in an enhancement effect, where the bioactivity of each is enhanced, creating a superior combination. This suggests that the combination of LMWF and GLM has the potential to offer a more potent and multifaceted therapeutic effect, particularly in the context of antioxidant and anti-inflammatory activities. These findings hold promise for the development of novel therapeutic interventions or supplements that harness the enhancement effects.

Keywords: combination, enhancement effect, perna canaliculus, undaria pinnatifida

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Authors: Alireza Barari, Ahmad Abdi

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Regular body trainings cause adaption in various system in body. One of the important effect of body training is its effect on immune system. It seems that cytokines usually release after long period exercises or some exercises which cause skeletal muscular damages. If some of the cytokines which cause responses such as inflammation of cells in skeletal muscles, with manipulating of training program, it can be avoided or limited from those exercises which induct cytokines release. Ginger plant is a kind of medicinal plants which is known as a anti inflammation plant. This plant is as most precedence medicinal plants in medicine science especially in inflammation cure. The aim of the present study was the effect of selected resistance training and consumption of ginger extract on IL-1α and TNFα untrained young women. The population includes young women interested in participating in the study with the average of 30±2 years old from Abbas Abad city among which 32 participants were chosen randomly and divided into 4 four groups, resistance training (R), resistance training and ginger consumption(RG), Ginger consumption(G)and Control group(C). The training groups performed circuit resistance training at the intensity of 65-75% one repeat maximum, 3 days a week for 6 weeks. Besides resistance training, subjects were given either ginseng (5 mg/kg per day) or placebo. Prior to and 48 hours after interventions body composition was measured and blood samples were taken in order to assess serum levels of IL-1α and TNFα. Plasma levels of cytokines were measured with commercially available ELISA Kits.IL-1α kit and TNFα kit were used in this research. To demonstrate the effectiveness of the independent variable and the comparison between groups, t-test and ANOVA were used. To determine differences between the groups, the Scheffe test was used that showed significant changes in any of the variables. we observed that circuit resistance training in R and RG groups can significant decreased in weight and body mass index in untrained females (p<0.05). The results showed a significant decreased in the mean level of IL-1α levels before and after the training period in G group (p=0.046) and RG group (p=0.022). Comparison between groups also showed there was significant difference between groups R-RG and RG-C. Intergroup comparison results showed that the mean levels of TNFα before and after the training in group G (p=0.044) and RG (p=0.037), significantly decreased. Comparison between groups also showed there was significant difference between groups R–RG , R-G ,RG-C and G-C. The research shows that circuit resistance training with reducing overload method results in systemic inflammation had significant effect on IL-1α levels and TNFα. Of course, Ginger can counteract the negative effects of resistance training exercise on immune function and stability of the mast cell membrane. Considerable evidence supported the anti-inflammatory properties of ginger for several constituents, especially gingerols, shogaols, paradols, and zingerones, through decreased cytokine gene TNF α and IL-1Α expression and inhibition of cyclooxygenase 1 and 2. These established biological actions suggest that ingested ginger could block the increase in IL-1α.

Keywords: resistance training, ginger, IL-1α , TNFα

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Authors: Ghada Al-Kafaji, Mohamed Sabry

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Mitochondria are the site of cellular respiration and produce energy in the form of adenosine triphosphate (ATP) via oxidative phosphorylation. They are the major source of intracellular reactive oxygen species (ROS) and are also direct target to ROS attack. Oxidative stress and ROS-mediated disruptions of mitochondrial function are major components involved in the pathogenicity of diabetic complications. In this work, the changes in mitochondrial DNA (mtDNA) copy number, biogenesis, gene expression of mtDNA-encoded subunits of electron transport chain (ETC) complexes, and mitochondrial function in response to hyperglycemia-induced ROS and the effect of direct inhibition of ROS on mitochondria were investigated in an in vitro model of diabetic nephropathy using human renal mesangial cells. The cells were exposed to normoglycemic and hyperglycemic conditions in the presence and absence of Mn(III)tetrakis(4-benzoic acid) porphyrin chloride (MnTBAP) or catalase for 1, 4 and 7 days. ROS production was assessed by the confocal microscope and flow cytometry. mtDNA copy number and PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 transcripts, were all analyzed by real-time PCR. PGC-1a, NRF-1, and TFAM, as well as ND2, CYTB, COI, and ATPase 6 proteins, were analyzed by Western blotting. Mitochondrial function was determined by assessing mitochondrial membrane potential and adenosine triphosphate (ATP) levels. Hyperglycemia-induced a significant increase in the production of mitochondrial superoxide and hydrogen peroxide at day 1 (P < 0.05), and this increase remained significantly elevated at days 4 and 7 (P < 0.05). The copy number of mtDNA and expression of PGC-1a, NRF-1, and TFAM as well as ND2, CYTB, CO1 and ATPase 6 increased after one day of hyperglycemia (P < 0.05), with a significant reduction in all those parameters at 4 and 7 days (P < 0.05). The mitochondrial membrane potential decreased progressively at 1 to 7 days of hyperglycemia with the parallel progressive reduction in ATP levels over time (P < 0.05). MnTBAP and catalase treatment of cells cultured under hyperglycemic conditions attenuated ROS production reversed renal mitochondrial oxidative stress and improved mtDNA, mitochondrial biogenesis, and function. These results show that hyperglycemia-induced ROS caused an early increase in mtDNA copy number, mitochondrial biogenesis and mtDNA-encoded gene expression of the ETC subunits in human mesangial cells as a compensatory response to the decline in mitochondrial function, which precede the mtDNA defect and mitochondrial dysfunction with a progressive oxidative response. Protection from ROS-mediated damage to renal mitochondria induced by hyperglycemia may be a novel therapeutic approach for the prevention/treatment of DN.

Keywords: diabetic nephropathy, hyperglycemia, reactive oxygen species, oxidative stress, mtDNA, mitochondrial dysfunction, manganese superoxide dismutase, catalase

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Authors: Jyoti Singh, Ranju Bansal

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Fighting pain and inflammation is a common problem faced by physicians while dealing with a wide variety of diseases. Since ancient time nonsteroidal anti-inflammatory agents (NSAIDs) and opioids have been the cornerstone of treatment therapy, however, the usefulness of both these classes is limited due to severe side effects. NSAIDs, which are mainly used to treat mild to moderate inflammatory pain, induce gastric irritation and nephrotoxicity whereas opioids show an array of adverse reactions such as respiratory depression, sedation, and constipation. Moreover, repeated administration of these drugs induces tolerance to the analgesic effects and physical dependence. Further discovery of selective COX-2 inhibitors (coxibs) suggested safety without any ulcerogenic side effects; however, long-term use of these drugs resulted in kidney and hepatic toxicity along with an increased risk of secondary cardiovascular effects. The basic approaches towards inflammation and pain treatment are constantly changing, and researchers are continuously trying to develop safer and effective anti-inflammatory drug candidates for the treatment of different inflammatory conditions such as osteoarthritis, rheumatoid arthritis, ankylosing spondylitis, psoriasis and multiple sclerosis. Synthetic 3(2H)-pyridazinones constitute an important scaffold for drug discovery. Structure-activity relationship studies on pyridazinones have shown that attachment of a lactam at N-2 of the pyridazinone ring through a methylene spacer results in significantly increased anti-inflammatory and analgesic properties of the derivatives. Further introduction of the heterocyclic ring at lactam nitrogen results in improvement of biological activities. Keeping in mind these SAR studies, a new series of compounds were synthesized as shown in scheme 1 and investigated for anti-inflammatory, analgesic, anti-platelet activities and docking studies. The structures of newly synthesized compounds have been established by various spectroscopic techniques. All the synthesized pyridazinone derivatives exhibited potent anti-inflammatory and analgesic activity. Homoveratryl substituted derivative was found to possess highest anti-inflammatory and analgesic activity displaying 73.60 % inhibition of edema at 40 mg/kg with no ulcerogenic activity when compared to standard drugs indomethacin. Moreover, 2-substituted-4-benzo[d][1,3]dioxole-6-phenylpyridazin-3(2H)-ones derivatives did not produce significant changes in bleeding time and emerged as safe agents. Molecular docking studies also illustrated good binding interactions at the active site of the cyclooxygenase-2 (hCox-2) enzyme.

Keywords: anti-inflammatory, analgesic, pyridazin-3(2H)-one, selective COX-2 inhibitors

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Authors: Qing Zhang, Janak L. Pathak, Macro N. Helder, Richard T. Jaspers, Yin Xiao

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Introduction: Nanomaterial-based bone regeneration is greatly influenced by the immune microenvironment. Tissue-engineered nanomaterials mediate the inflammatory response of macrophages to regulate bone regeneration. Silica nanoparticles have been widely used in tissue engineering-related preclinical studies. However, the effect of topological features on the surface of silica nanoparticles on the immune response of macrophages remains unknown. Purposes: The aims of this research are to compare the influences of normal and pollen-like silica nano-surface topography on macrophage immune responses and to obtain insight into their potential regulatory mechanisms. Method: Macrophages (RAW 264.7 cells) were exposed to mesoporous silica nanoparticles with normal morphology (MSNs) and pollen-like morphology (PMSNs). RNA-seq, RT-qPCR, and LSCM were used to assess the changes in expression levels of immune response-related genes and proteins. SEM and TEM were executed to evaluate the contact and adherence of silica nanoparticles by macrophages. For the assessment of the immunomodulation-mediated osteogenic potential, BMSCs were cultured with conditioned medium (CM) from LPS pre-stimulated macrophage cultures treated with MSNs or PMSNs. Osteoimmunomodulatory potential of MSNs and PMSNs in vivo was tested in a mouse cranial bone osteolysis model. Results: The results of the RNA-seq, RT-qPCR, and LSCM assays showed that PMSNs inhibited the expression of pro-inflammatory genes and proteins in macrophages. SEM images showed distinct macrophage membrane surface binding patterns of MSNs and PMSNs. MSNs were more evenly dispersed across the macrophage cell membrane, while PMSNs were aggregated. PMSNs-induced macrophage anti-inflammatory response was associated with upregulation of the cell surface receptor CD28 and inhibition of ERK phosphorylation. TEM images showed that both MSNs and PMSNs could be phagocytosed by macrophages, and inhibiting nanoparticle phagocytosis did not affect the expression of anti-inflammatory genes and proteins. Moreover, PMSNs-induced conditioned medium from macrophages enhanced BMP-2 expression and osteogenic differentiation mBMSCs. Similarly, PMSNs prevented LPS-induced bone resorption via downregulation of inflammatory reaction. Conclusions: PMSNs can promote bone regeneration by modulating osteoimmunological processes through surface topography. The study offers insights into how surface physical contact cues can modulate the regulation of osteoimmunology and provides a basis for the application of nanoparticles with pollen-like morphology to affect immunomodulation in bone tissue engineering and regeneration.

Keywords: physical contact, osteoimmunology, macrophages, silica nanoparticles, surface morphology, membrane receptor, osteogenesis, inflammation

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Authors: Fatemeh Sadeghi, Peyman Sheikhzadeh

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Introduction: Block Sequential Regularized Expectation Maximization (BSREM) reconstruction algorithm was recently developed to suppress excessive noise by applying a relative difference penalty. The aim of this study was to investigate the effect of various strengths of noise penalization factor in the BSREM algorithm under different acquisition duration and lesion sizes in order to determine an optimum penalty factor by considering both quantitative and qualitative image evaluation parameters in clinical uses. Materials and Methods: The NEMA IQ phantom and 15 clinical whole-body patients with prostate cancer were evaluated. Phantom and patients were injected withGallium-68 Prostate-Specific Membrane Antigen(68 Ga-PSMA)and scanned on a non-time-of-flight Discovery IQ Positron Emission Tomography/Computed Tomography(PET/CT) scanner with BGO crystals. The data were reconstructed using BSREM with a β-value of 100-500 at an interval of 100. These reconstructions were compared to OSEM as a widely used reconstruction algorithm. Following the standard NEMA measurement procedure, background variability (BV), recovery coefficient (RC), contrast recovery (CR) and residual lung error (LE) from phantom data and signal-to-noise ratio (SNR), signal-to-background ratio (SBR) and tumor SUV from clinical data were measured. Qualitative features of clinical images visually were ranked by one nuclear medicine expert. Results: The β-value acts as a noise suppression factor, so BSREM showed a decreasing image noise with an increasing β-value. BSREM, with a β-value of 400 at a decreased acquisition duration (2 min/ bp), made an approximately equal noise level with OSEM at an increased acquisition duration (5 min/ bp). For the β-value of 400 at 2 min/bp duration, SNR increased by 43.7%, and LE decreased by 62%, compared with OSEM at a 5 min/bp duration. In both phantom and clinical data, an increase in the β-value is translated into a decrease in SUV. The lowest level of SUV and noise were reached with the highest β-value (β=500), resulting in the highest SNR and lowest SBR due to the greater noise reduction than SUV reduction at the highest β-value. In compression of BSREM with different β-values, the relative difference in the quantitative parameters was generally larger for smaller lesions. As the β-value decreased from 500 to 100, the increase in CR was 160.2% for the smallest sphere (10mm) and 12.6% for the largest sphere (37mm), and the trend was similar for SNR (-58.4% and -20.5%, respectively). BSREM visually was ranked more than OSEM in all Qualitative features. Conclusions: The BSREM algorithm using more iteration numbers leads to more quantitative accuracy without excessive noise, which translates into higher overall image quality and lesion detectability. This improvement can be used to shorter acquisition time.

Keywords: BSREM reconstruction, PET/CT imaging, noise penalization, quantification accuracy

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Authors: Tahisa M. Pedroso, Hérida R. N. Salgado

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The microbiological turbidimetric assay allows the determination of potency of the drug, by measuring the turbidity (absorbance), caused by inhibition of microorganisms by ertapenem sodium. Ertapenem sodium (ERTM), a synthetic antimicrobial agent of the class of carbapenems, shows action against Gram-negative, Gram-positive, aerobic and anaerobic microorganisms. Turbidimetric assays are described in the literature for some antibiotics, but this method is not described for ertapenem. The objective of the present study was to develop and validate a simple, sensitive, precise and accurate microbiological assay by turbidimetry to quantify ertapenem sodium injectable as an alternative to the physicochemical methods described in the literature. Several preliminary tests were performed to choose the following parameters: Staphylococcus aureus ATCC 25923, IAL 1851, 8 % of inoculum, BHI culture medium, and aqueous solution of ertapenem sodium. 10.0 mL of sterile BHI culture medium were distributed in 20 tubes. 0.2 mL of solutions (standard and test), were added in tube, respectively S1, S2 and S3, and T1, T2 and T3, 0.8 mL of culture medium inoculated were transferred to each tube, according parallel lines 3 x 3 test. The tubes were incubated in shaker Marconi MA 420 at a temperature of 35.0 °C ± 2.0 °C for 4 hours. After this period, the growth of microorganisms was inhibited by addition of 0.5 mL of 12% formaldehyde solution in each tube. The absorbance was determined in Quimis Q-798DRM spectrophotometer at a wavelength of 530 nm. An analytical curve was constructed to obtain the equation of the line by the least-squares method and the linearity and parallelism was detected by ANOVA. The specificity of the method was proven by comparing the response obtained for the standard and the finished product. The precision was checked by testing the determination of ertapenem sodium in three days. The accuracy was determined by recovery test. The robustness was determined by comparing the results obtained by varying wavelength, brand of culture medium and volume of culture medium in the tubes. Statistical analysis showed that there is no deviation from linearity in the analytical curves of standard and test samples. The correlation coefficients were 0.9996 and 0.9998 for the standard and test samples, respectively. The specificity was confirmed by comparing the absorbance of the reference substance and test samples. The values obtained for intraday, interday and between analyst precision were 1.25%; 0.26%, 0.15% respectively. The amount of ertapenem sodium present in the samples analyzed, 99.87%, is consistent. The accuracy was proven by the recovery test, with value of 98.20%. The parameters varied did not affect the analysis of ertapenem sodium, confirming the robustness of this method. The turbidimetric assay is more versatile, faster and easier to apply than agar diffusion assay. The method is simple, rapid and accurate and can be used in routine analysis of quality control of formulations containing ertapenem sodium.

Keywords: ertapenem sodium, turbidimetric assay, quality control, validation

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Authors: Neha P. Amin, Maliha Zainib, Sean Parker, Malcolm Mattes

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Purpose/Objectives: Combination immunotherapy (IT) and radiation therapy (RT) is an actively growing field of clinical investigation due to promising findings of synergistic effects from immune-mediated mechanisms observed in preclinical studies and clinical data from case reports of abscopal effects. While there are many ongoing trials of combined IT-RT, there are still limited data on toxicity and outcome optimization regarding RT dose, fractionation, and sequencing of RT with IT. Nivolumab (NIVO), an anti-PD-1 monoclonal antibody, has been rapidly adopted in the clinic over the past 2 years, resulting in more patients being considered for concurrent RT-NIVO. Knowledge about the toxicity profile of combined RT-NIVO is important for both the patient and physician when making educated treatment decisions. The acute toxicity profile of concurrent RT-NIVO was analyzed in this study. Materials/Methods: A retrospective review of all consecutive patients who received NIVO from 1/2015 to 5/2017 at 4 separate centers within two separate institutions was performed. Those patients who completed a course of RT from 1 day prior to initial NIVO infusion through 1 month after last NIVO infusion were considered to have received concurrent therapy and included in the subsequent analysis. Descriptive statistics are reported for patient/tumor/treatment characteristics and observed acute toxicities within 3 months of RT completion. Results: Among 261 patients who received NIVO, 46 (17.6%) received concurrent RT to 67 different sites. The median f/u was 3.3 (.1-19.8) months, and 11/46 (24%) were still alive at last analysis. The most common histology, RT prescription, and treatment site included non-small cell lung cancer (23/46, 50%), 30 Gy in 10 fractions (16/67, 24%), and central thorax/abdomen (26/67, 39%), respectively. 79% (53/67) of irradiated sites were treated with 3D-conformal technique and palliative dose-fractionation. Grade 3, 4, and 5 toxicities were experienced by 11, 1, and 2 patients, respectively. However all grade 4 and 5 toxicities were outside of the irradiated area and attributed to the NIVO alone, and only 4/11 (36%) of the grade 3 toxicities were attributed to the RT-NIVO. The irradiated site in these cases included the brain [2/10 (20%)] and central thorax/abdomen [2/19 (10.5%)], including one unexpected grade 3 pancreatitides following stereotactic body RT to the left adrenal gland. Conclusions: Concurrent RT-NIVO is generally well tolerated, though with potentially increased rates of severe toxicity when irradiating the lung, abdomen, or brain. Pending more definitive data, we recommend counseling patients on the potentially increased rates of side effects from combined immunotherapy and radiotherapy to these locations. Future prospective trials assessing fractionation and sequencing of RT with IT will help inform combined therapy recommendations.

Keywords: combined immunotherapy and radiation, immunotherapy, Nivolumab, toxicity of concurrent immunotherapy and radiation

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Authors: Syed Asif Hassan, Tabrej Khan

Abstract:

Tuberculosis (TB) caused by bacillus Mycobacterium tuberculosis (Mtb) continues to take a disturbing toll on human life and healthcare facility worldwide. The global burden of TB remains enormous. The alarming rise of multi-drug resistant strains of Mycobacterium tuberculosis calls for an increase in research efforts towards the development of new target specific therapeutics against diverse strains of M. tuberculosis. Therefore, the discovery of new molecular scaffolds targeting new drug sites should be a priority for a workable plan for fighting resistance in Mycobacterium tuberculosis (Mtb). Mtb non-acylated lipoprotein LprG (Rv1411c) has a Toll-like receptor 2 (TLR2) agonist actions that depend on its association with triacylated glycolipids binding specifically with the hydrophobic pocket of Mtb LprG lipoprotein. The detection of a glycolipid carrier function has important implications for the role of LprG in Mycobacterial physiology and virulence. Therefore, considering the pivotal role of glycolipids in mycobacterial physiology and host-pathogen interactions, designing competitive antagonist (chemotherapeutics) ligands that competitively bind to glycolipid binding domain in LprG lipoprotein, will lead to inhibition of tuberculosis infection in humans. In this study, a unified approach involving ligand-based virtual screening protocol USRCAT (Ultra Shape Recognition) software and molecular docking studies using Auto Dock Vina 1.1.2 using the X-ray crystal structure of Mtb LprG protein was implemented. The docking results were further confirmed by DSX (DrugScore eXtented), a robust program to evaluate the binding energy of ligands bound to the Ligand binding domain of the Mtb LprG lipoprotein. The ligand, which has the higher hypothetical affinity, also has greater negative value. Based on the USRCAT, Lipinski’s values and molecular docking results, [(2R)-2,3-di(hexadecanoyl oxy)propyl][(2S,3S,5S,6R)-3,4,5-trihydroxy-2,6-bis[[(2R,3S,4S,5R,6S)-3,4,5-trihydroxy-6 (hydroxymethyl)tetrahydropyran-2-yl]oxy]cyclohexyl] phosphate (XPX) was confirmed as a promising drug-like lead compound (antagonist) binding specifically to the hydrophobic domain of LprG protein with affinity greater than that of PIM2 (agonist of LprG protein) with a free binding energy of -9.98e+006 Kcal/mol and binding affinity of -132 Kcal/mol, respectively. A further, in vitro assay of this compound is required to establish its potency in inhibiting molecular evasion mechanism of MTB within the infected host macrophages. These results will certainly be helpful in future anti-TB drug discovery efforts against Multidrug-Resistance Tuberculosis (MDR-TB).

Keywords: antagonist, agonist, binding affinity, chemotherapeutics, drug-like, multi drug resistance tuberculosis (MDR-TB), RV1411c protein, toll-like receptor (TLR2)

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Authors: Asghar Arif

Abstract:

Lung cancer has been recognized as one of the greatest common cancers, causing the annual mortality rate of about 1.2 million people in the world. Lung cancer is the most prevalent cancer in men and the third-most common cancer among women (after breast and digestive cancers).Recent evidences have shown the inflammatory process as one of the potential factors of cancer. Tuberculosis (TB), pneumonia, and chronic bronchitis are among the most important inflammation-inducing factors in the lungs, among which TB has a more profound role in the emergence of cancer.TB is one of the important mortality factors throughout the world, and 205,000 death cases are reported annually due to this disease. Chronic inflammation and fibrosis due to TB can induce genetic mutation and alternations. Parenchyma tissue of lung is involved in both diseases of TB and lung cancer, and continuous cough in lung cancer, morphological vascular variations, lymphocytosis processes, and generation of immune system mediators such as interleukins, are all among the factors leading to the hypothesis regarding the role of TB in lung cancer Some reports have shown that the induction of necrosis and apoptosis or TB reactivation, especially in patients with immune-deficiency, may result in increasing IL-17 and TNF_α, which will either decrease P53 activity or increase the expression of Bcl-2, decrease Bax-T, and cause the inhibition of caspase-3 expression due to decreasing the expression of mitochondria cytochrome oxidase. It has been also indicated that following the injection of BCG vaccine, the host immune system will be reinforced, and in particular, the rates of gamma interferon, nitric oxide, and interleukin-2 are increased. Therefore, CD4 + lymphocyte function will be improved, and the person will be immune against cancer.Numerous prospective studies have so far been conducted on the role of TB in lung cancer, and it seems that this disease is effective in that particular cancer.One of the main challenges of lung cancer is its correct and timely diagnosis. Unfortunately, clinical symptoms (such as continuous cough, hemoptysis, weight loss, fever, chest pain, dyspnea, and loss of appetite) and radiological images are similar in TB and lung cancer. Therefore, anti-TB drugs are routinely prescribed for the patients in the countries with high prevalence of TB, like Pakistan. Regarding the similarity in clinical symptoms and radiological findings of lung cancer, proper diagnosis is necessary for TB and respiratory infections due to nontuberculousmycobacteria (NTM). Some of the drug resistive TB cases are, in fact, lung cancer or NTM lung infections. Acid-fast staining and histological study of phlegm and bronchial washing, culturing and polymerase chain reaction TB are among the most important solutions for differential diagnosis of these diseases. Briefly, it is assumed that TB is one of the risk factors for cancer. Numerous studies have been conducted in this regard throughout the world, and it has been observed that there is a significant relationship between previous TB infection and lung cancer. However, to prove this hypothesis, further and more extensive studies are required. In addition, as the clinical symptoms and radiological findings of TB, lung cancer, and non-TB mycobacteria lung infections are similar, they can be misdiagnosed as TB.

Keywords: TB and lung cancer, TB people, TB servivers, TB and HIV aids

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Authors: Raudone Lina, Raudonis Raimondas, Liaudanskas Mindaugas, Pukalskas Audrius, Viskelis Pranas, Janulis Valdimaras

Abstract:

Human health fortification, its protection and disease prophylaxis are the main problems of the health care systems. Plant origin materials and their preparations are applied for the prevention of the common diseases. Oxidative stress takes part in the pathogenesis of many autoimmune, neurodegenerative, tumor and ageing processes. The antioxidants are able to protect the human body from the free radicals and to stop the progression of numerous chronic diseases. The research of plant origin materials is relevant for the search of natural antioxidants. A group of compounds that gained scientific attention due to antioxidant properties and effects on human health are phenolic compounds. Phenolic compounds are widely abundant in various parts of plants, i.e. leaves, stems, roots, flowers and fruits. Most commonly consumed fruits all over the world are apples. It is very important to analyze the antioxidant activity of apples as they are extensively used in the prevention of various diseases. The aim of this study was to determine the antioxidant profiles of Malus domestica Borkh fruit cultivars (Aldas, Auksis, Connel Red, Ligol, Lodel, Rajka) and to identify the phenolic compounds with potent contribution to antioxidant activity. Nineteen constituents were identified in apple cultivars using ultra high performance liquid chromatography coupled to quadruple and time-of-flight mass spectrometers (UPLC–QTOF–MS). Phytochemical profile was constituted of phenolic acids, procyanidins, quercetin derivatives and dihydrochalcones. Reducing and radical scavenging activities of individual constituents were determined using high performance liquid chromatography (HPLC) coupled to post-column FRAP and ABTS assay, respectively. Significant differences of total radical scavenging and reducing activity (expressed as trolox equivalents, TE µmol/g) were determined between the investigated cultivars. Chlorogenic acid and complex of procyanidins were the main contributors to antioxidant activity determining up to 35 % and 55 % of total TE values, respectively. Determined phenolic composition and antioxidant activity significantly depend on apple cultivars. It is important to determine the individual compounds that are significant for antioxidant activity and that could be investigated in vivo systems. The identification of the antioxidants provides information for the further research of standardized extracts that could be used for pharmaceutical preparations with specific phenolic traits.

Keywords: FRAP, ABTS, antioxidant, phenolic, apples, chlorogenic acid

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Authors: Peter J. Fusco, Dave M. Mathew, Chris Mathew, Kenneth H. Levy, Kathryn S. Varghese, Stephanie Salazar-Restrepo, Serena M. Mathew, Sofia Khaja, Eamon Vega, Mia Polizzi, Alyssa Mullane, Adham Ahmed

Abstract:

Background: Laparoscopic (LS) removal of neuroblastomas in children has been reported to offer favorable outcomes compared to the conventional open thoracotomy (OT) procedure. Critical perioperative measures such as blood loss, operative time, length of stay, and time to postoperative chemotherapy have all supported laparoscopic use rather than its more invasive counterpart. Herein, a pairwise meta-analysis was performed comparing perioperative outcomes between LS and OT in thoracoabdominal neuroblastoma cases. Methods: A comprehensive literature search was performed on PubMed, Ovid EMBASE, and Scopus databases to identify studies comparing the outcomes of pediatric patients with thoracoabdominal neuroblastomas undergoing resection via OT or LS. After deduplication, 4,227 studies were identified and subjected to initial title screening with exclusion and inclusion criteria to ensure relevance. When studies contained overlapping cohorts, only the larger series were included. Primary outcomes include estimated blood loss (EBL), hospital length of stay (LOS), and mortality, while secondary outcomes were tumor recurrence, post-operative complications, and operation length. The “meta” and “metafor” packages were used in R, version 4.0.2, to pool risk ratios (RR) or standardized mean differences (SMD) in addition to their 95% confidence intervals in the random effects model via the Mantel-Haenszel method. Heterogeneity between studies was assessed using the I² test, while publication bias was assessed via funnel plot. Results: The pooled analysis included 209 patients from 5 studies (141 OT, 68 LS). Of the included studies, 2 originated from the United States, 1 from Toronto, 1 from China, and 1was from a Japanese center. Mean age between study cohorts ranged from 2.4 to 5.3 years old, with female patients occupying between 30.8% to 50% of the study populations. No statistically significant difference was found between the two groups for LOS (SMD -1.02; p=0.083), mortality (RR 0.30; p=0.251), recurrence(RR 0.31; p=0.162), post-operative complications (RR 0.73; p=0.732), or operation length (SMD -0.07; p=0.648). Of note, LS appeared to be protective in the analysis for EBL, although it did not reach statistical significance (SMD -0.4174; p= 0.051). Conclusion: Despite promising literature assessing LS removal of pediatric neuroblastomas, results showed it was non-superior to OT for any explored perioperative outcomes. Given the limited comparative data on the subject, it is evident that randomized trials are necessary to further the efficacy of the conclusions reached.

Keywords: laparoscopy, neuroblastoma, thoracoabdominal, thoracotomy

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