Search results for: tumor inhibition

Authors: Shakir H. Mohammed Al-Alwany, Saad Hasan M. Ali, Ibrahim Mohammed S. Shnawa

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The study was aimed to define the percentage of detection of high-oncogenic risk types of HPV and their genotyping in archival tissue specimens that ranged from apparently healthy tissue to invasive breast cancer by using one of the recent versions of In Situ Hybridization(ISH) 0.2. To find out rational significance of such genotypes as well as over expressed products of mutants P53 and RB genes on the severity of underlying breast cancers. The DNA of HPV was detected in 46.5 % of tissues from breast cancers while HPV DNA in the tissues from benign breast tumours was detected in 12.5%. No HPV positive–ISH reaction was detected in healthy breast tissues of the control group. HPV DNA of genotypes (16, 18, 31 and 33) was detected in malignant group in frequency of 25.6%, 27.1%, 30.2% and 12.4%, respectively. Over expression of p53 was detected by IHC in 51.2% breast cancer cases and in 50% benign breast tumour group, while none of control group showed P53- over expression. Retinoblastoma protein was detected by IHC test in 49.7% of malignant breast tumours, 54.2% of benign breast tumours but no signal was reported in the tissues of control group. The significance prevalence of expression of mutated p53 & Rb genes as well as detection of high-oncogenic HPV genotypes in patients with breast cancer supports the hypothesis of an etiologic role for the virus in breast cancer development.

Keywords: human papilloma virus, P53, RB, breast cancer

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Authors: Aditya Karade, Sharada Falane, Dhananjay Deshmukh, Vijaykumar Mantri

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Brain tumors pose a significant challenge in healthcare due to their complex nature and impact on patient outcomes. The application of deep learning (DL) algorithms in medical imaging have shown promise in accurate and efficient brain tumour detection. This paper explores the performance of various pre-trained DL models ResNet50, Xception, InceptionV3, EfficientNetB0, DenseNet121, NASNetMobile, VGG19, VGG16, and MobileNet on a brain tumour dataset sourced from Figshare. The dataset consists of MRI scans categorizing different types of brain tumours, including meningioma, pituitary, glioma, and no tumour. The study involves a comprehensive evaluation of these models’ accuracy and effectiveness in classifying brain tumour images. Data preprocessing, augmentation, and finetuning techniques are employed to optimize model performance. Among the evaluated deep learning models for brain tumour detection, ResNet50 emerges as the top performer with an accuracy of 98.86%. Following closely is Xception, exhibiting a strong accuracy of 97.33%. These models showcase robust capabilities in accurately classifying brain tumour images. On the other end of the spectrum, VGG16 trails with the lowest accuracy at 89.02%.

Keywords: brain tumour, MRI image, detecting and classifying tumour, pre-trained models, transfer learning, image segmentation, data augmentation

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Authors: Azhar Jabareen, Mahmoud Huleihel

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BRCA-1 is a multifunctional tumor suppressor, whose expression is activated by the estrogen (E2)-liganded ERα receptor. The activated ERα is a transcriptional factor which activates various genes either by direct binding to the DNA at E2-responsive elements (EREs) and indirectly associated with a range of alternative non-ERE elements. Interference with BRCA-1 expression and/or functions leads to high risk of breast or/and ovarian cancer. Our lab investigated the involvement of Human T-cell leukemia Virus Type 1 (HTLV-1) in breast cancer, since HTLV-1 Tax was found to strongly inhibit BRCA-1 expression. In addition, long exposure of 12-O-tetradecanoylphorbol-13-acetate (TPA), which is one of the stress-inducing agents activated the HTLV-1 promoter. So here the involvement of TPA in breast cancer had been examined by testing the effect of TPA on BRCA-1 and ERE expression. The results showed that TPA activated both BRCA-1 and ERE expression. In the 12 hours TPA activated the tow promoters more than others time, and after 24 hours the level of the tow promoters was decreased. Tax inhibited BRCA-1 expression but did not succeed to inhibit the effect of TPA. Then the activation of the two promoters was not through ERα pathway because TPA had no effect on ERα binding to the two promoters of the BRCA-1 and ERE. Also, the activation was not via nuclear factor kappa B (NF-κB) pathway because when the inhibitory of NF-κB had been added to the TPA, it still activated the tow promoters. However, it seems that 53BP1 may be involved in TPA activation of these promoters because ectopic high expression of 53BP1 significantly reduced the TPA activity. In addition, in the presence of Bisindolylmaleimide-I (BI)- the inhibitor of Protein Kinase C (PKC)- there was no activation for the two promoters, so the PKC is agonized BRCA-1 and ERE activation.

Keywords: BRCA-1, ERE, HTLV-1, TPA

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Authors: Chengcao Sun, Shujun Li, Cuili Yang, Yongyong Xi, Liang Wang, Feng Zhang, Dejia Li

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Recently, the long non-coding RNA (lncRNA) NEAT1 has been identified as an oncogenic gene in multiple cancer types and elevated expression of NEAT1 was tightly linked to tumorigenesis and cancer progression. However, the molecular basis for this observation has not been characterized in progression of non-small cell lung cancer (NSCLC). In our studies, we identified NEAT1 was highly expressed in NSCLC patients and was a novel regulator of NSCLC progression. Patients whose tumors had high NEAT1 expression had a shorter overall survival than patients whose tumors had low NEAT1 expression. Further, NEAT1 significantly accelerates NSCLC cell growth and metastasis in vitro and tumor growth in vivo. Additionally, by using bioinformatics study and RNA pull down combined with luciferase reporter assays, we demonstrated that NEAT1 functioned as a competing endogenous RNA (ceRNA) for has-miR-377-3p, antagonized its functions and led to the de-repression of its endogenous targets E2F3, which was a core oncogene in promoting NSCLC progression. Taken together, these observations imply that the NEAT1 modulated the expression of E2F3 gene by acting as a competing endogenous RNA, which may build up the missing link between the regulatory miRNA network and NSCLC progression.

Keywords: long non-coding RNA NEAT1, hsa-miRNA-377-3p, E2F3, non-small cell lung cancer, tumorigenesis

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Authors: Ivar Zekker, Ergo Rikmann, Anni Mandel, Markus Raudkivi, Kristel Kroon, Liis Loorits, Andrus Seiman, Hannu Fritze, Priit Vabamäe, Toomas Tenno, Taavo Tenno

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The anaerobic ammonium oxidation (anammox) and nitritation-anammox (deammonification) processes are widely used for N-rich wastewater treatment nowadays. A deammonification moving bed biofilm reactor (MBBR) with a high maximum total nitrogen removal rate (TNRR) of 1.5 g N m-2 d-1 was started up and similarly high TNRR was sustained at low temperature of 15°C. During biofilm cultivation, temperature in MBBR was lowered by 0.5° C week-1 sustaining the high TNRR. To study the short-term effect of temperature on the TNRR, a series of batch-scale experiments performed showed sufficient TNRRs even at 9-15° C (4.3-5.4 mg N L-1 h-1, respectively). After biomass was adapted to lower temperature (15°C), the TNRR increase at lower temperature (15°C) was relatively higher (15-20%) than with biomass adapted to higher temperatures (17-18°C). Anammox qPCR showed increase of Candidatus Brocadia quantities from 5×103 to 1×107 anammox gene copies g-1 TSS despite temperature lowered to 15°C. Modeling confirmed causes of stable and unstable periods in the reactor and in batch test high Arrhenius constant of 29.7 kJ mol-1 of the process as high as at 100 mg NO2--N L-1 were determined. 

Keywords: deammonification, reject water, intermittent aeration, nitrite inhibition

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Authors: Veronica Sorgato, Jeremy Belhassen, Philippe Chartier, Roddy Sihanath, Nicolas Docquiere, Jean-Yves Giraud

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We analyzed the image-guided radiotherapy method used by the TomoTherapy® System (Accuray Corp.) for patient repositioning in clinical routine. The TomoTherapy® System computes X, Y, Z and roll displacements to match the reference CT, on which the dosimetry has been performed, with the pre-treatment MV CT. The accuracy of the repositioning method has been studied according to the treatment localization. For this, a database of 18774 treatment sessions, performed during 2 consecutive years (2016-2017 period) has been used. The database includes the X, Y, Z and roll displacements proposed by TomoTherapy® System as well as the manual correction of these proposals applied by the radiation therapist. This manual correction aims to further improve the repositioning based on the clinical situation and depends on the structures surrounding the target tumor tissue. The statistical analysis performed on the database aims to define repositioning limits to be used as security and guiding tool for the manual adjustment implemented by the radiation therapist. This tool will participate not only to notify potential repositioning errors but also to further improve patient positioning for optimal treatment.

Keywords: accuracy, IGRT MVCT, image-guided radiotherapy megavoltage computed tomography, statistical analysis, tomotherapy, localization

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Authors: Hatem A. El-Mezayen, Hossam Darwesh

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Background/Aim: Hepatocellular carcinoma (HCC) is often diagnosed at advanced stage where effective therapies are lacking. Identification of new scoring system is needed to discriminate HCC patients from those with chronic liver disease. Based on the link between vascular endothelial growth factor (VEGF) and HCC progression, we aimed to develop a novel score based on combination of VEGF and routine laboratory tests for early prediction of HCC. Methods: VEGF was assayed for HCC group (123), liver cirrhosis group (210) and control group (50) by Enzyme Linked Immunosorbent Assay (ELISA). Data from all groups were retrospectively analyzed including α feto protein (AFP), international normalized ratio (INR), albumin and platelet count, transaminases, and age. Areas under ROC curve were used to develop the score. Results: A novel index named hepatocellular carcinoma-vascular endothelial growth factor score (HCC-VEGF score)=1.26 (numerical constant) + 0.05 ×AFP (U L-1)+0.038 × VEGF(ng ml-1)+0.004× INR –1.02 × Albumin (g l-1)–0.002 × Platelet count × 109 l-1 was developed. HCC-VEGF score produce area under ROC curve of 0.98 for discriminating HCC patients from liver cirrhosis with sensitivity of 91% and specificity of 82% at cut-off 4.4 (ie less than 4.4 considered cirrhosis and greater than 4.4 considered HCC). Conclusion: Hepatocellular carcinoma-VEGF score could replace AFP in HCC screening and follow up of cirrhotic patients.

Keywords: Hepatocellular carcinoma, cirrhosis, HCV, diagnosis, tumor markers

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Authors: A. Lardjam, R. Mazid, S. Y. Boudghene, A. Izarouken, Y. Dali, N. Djebli, H. Toumi

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Origanum glandulosum is an aromatic plant, common in Algeria and widely used by local people for its medicinal properties. The essential oil from this plant, which grows in the west of Algeria, was studied to evaluate and determine its antibacterial activity. The extraction of the essential oil was performed by water steam distillation; the yield obtained from the aerial parts (1.78 %) is interesting, its chromatographic profile revealed by TLC showed the presence of phenolic compounds thymol and carvacrol. The evaluation of the activity of the essential oil of Origanum glandulosum on bacterial strains of hospital origin, ATCC, MRB, and HRB, most implicated in nosocomial infections (Staphylococcus aureus ATCC 25923, Staphylococcus aureus ATCC 43300, Enterococcus faecalis ATCC 29212, Escherichia coli ATCC 25922, Pseudomonas aeruginosa ATCC 27853, Staphylococcus aureus resistant to meticillin, Enterococcus faecium, VA R and R TEC, Acinetobacter baumanii, IMP R and R CAZ, Klebsiella pneumonia carbapenemase-producing) by the method of aromatogramme and micro atmosphere, shows that the antibacterial potency of this oil is very high, expressed by significant inhibition diameters on all strains except Pseudomonas aeruginosa, and low MICs and is characterized by a bactericidal action.

Keywords: antibacterial activity, essential oil, HRB, MBR, nosocomial infections, origanum glandulosum

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Authors: Yomna T. Abdou, Hala F. Zaki, Sanaa A. Kenawy

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Naringenin is a flavanone, a type of flavonoid, found in fruits such as grapefruit, oranges, and tomatoes, was found to possess antioxidant, anti-inflammatory and antitumor effects. The present study was conducted to investigate the protective effect of naringenin on iodoacetamide-induced ulcerative colitis (UC) in rats. Male Wistar rats were pretreated with sulfasalazine (300 mg/kg, p.o.) as standard anti-inflammatory drug or naringenin (50 mg/kg, p.o.) for 7 consecutive days then UC was induced by intracolon administration of 0.1 ml (2%) iodoacetamide dissolved in 1% methylcelluose. One week later, animals were scarificed and the colonic tissues were dissected. Colon inflammation was evident by elevation in colon tumor necrosis factor alpha (TNFα) and interleukin-8 (IL-8) as well as inducible nitric oxide synthase (iNOS) enzyme, prostaglandin- E2 (PG-E2) and myeloperoxidase (MPO) activities. Additionally, oxidative stress was manifested by increased colon lipoperoxidation (MDA), glutathione (GSH) depletion, elevated nitric oxide (NO) content and glutathione peroxidase (GPx) activity. Pretreatment with naringenin largely mitigated these alterations. The present study reinforces the hypothetical use of naringenin as an anti-inflammatory complement to conventional UC treatment and could be considered in the dietary prevention of intestinal inflammation and related disorders.

Keywords: iodoacetamide, naringenin, sulfasalazine, ulcerative colitis

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Authors: Pun Jankrajangjaeng

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Senna garrettiana is a climatic tropical plant in Southeast Asia. Senna garrettiana (Craib) is used as a medicinal plant in Thailand, in which the experiment reported that the plant contains triterpenoids, ligans, phenolics, and fungal metabolites. Thus, it is also reported that the plant possesses interesting biological activity such as antioxidant activity. Therefore, Senna garrettiana is selected to examine the antimicrobial activity. The purpose of this study is to examine the antimicrobial activity of Senna garrettiana (crab) extract against Gram-positive Staphylococcus aureus and Gram-negative Salmonella typhi, and the fungus Candida albicans. This study performed the agar disk-diffusion method and broth microdilution by using five concentrations of plant extract to determine the minimum inhibitory concentration (MIC) of S. garrettiana extract. The result showed that S. garrettiana extract gave the maximum zone inhibition of 11.7 mm, 13.7 mm, and 14.0 mm against S. aureus, S. typhi, and C. albicans, respectively. The MIC value of S. garrettiana against S. aureus was 125 µg/mL while the MIC in S. typhi and C. albicans greater than 2000 µg/mL. To conclude, S. garrettiana extract showed higher sensitivity of antibacterial activity against gram-positive bacteria than gram-negative bacteria. In addition, the plant extracts also possessed antifungal activity. Therefore, further investigation to confirm the mechanism of action of antimicrobial activity in S. garrettiana extract should be performed to identify the target of the antimicrobial action.

Keywords: antimicrobial activity, Candida albicans, Salmonella typhi, Senna garrettiana, Staphylococcus aureus

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Authors: I. Iroka, L. Mgidlana, J. Willoughby, S. Dhlamini, P. Nxumalo, S. Sefadi, A. Mthembu, E. Gerber, E. Brits

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Introduction: Nephroblastoma is a common paediatric tumor with good survival rates when diagnosed and treated early. Method: This retrospective study aimed to describe the patients with nephroblastoma seen at Universitas Academic Hospital Complex between the years 2000 and 2020. Results: In the study period, there were 207 patients identified. The patient profile had slightly more male than female patients; the median age was under four years of age. The study found a median delay of one month between symptom onset and diagnosis; a common cause was a delay in seeking care. Patients diagnosed and treated more than a month after symptoms started had poorer survival rates. There was a higher rate of Stage IV disease compared to similar studies in South Africa. Good preoperative histology and no relapse had good survival rates.. Patients from Lesotho had longer delays and presented with more severe diseases than the South African cohort. Conclusion: Early identification and treatment lead to better outcomes. Health-seeking behaviour, misdiagnosis, and referral delays might contribute to the long delays. A targeted study for patients from Lesotho is recommended.

Keywords: nephroblastoma, South Africa, Lesotho, developing country

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Authors: Nighat Bibi, Jane Courtney, Kathleen M. Curran

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Magnetic Resonance Imaging (MRI) is essential for the differential diagnosis of brain diseases, with deep learning methods showing promise for enhancing diagnostic accuracy. This study develops an ensemble learning model incorporating DenseNet121, EfficientNetB1, and ResNet50 architectures for the accurate classification of diverse brain conditions, including glioma, meningioma, pituitary tumors, and multiple sclerosis (MS). The model is trained on publicly available MRI datasets, utilizing Gradient-weighted Class Activation Mapping (Grad-CAM) to increase interpretability by highlighting crucial image regions, thereby enhancing transparency in AI-assisted diagnostics. The ensemble model achieved a notable classification accuracy of 99.84%, demonstrating its reliability in distinguishing multiple brain conditions. Grad-CAM visualizations further support the model’s decision-making, fostering trust in clinical applications. This approach offers a valuable tool for MRI-based diagnosis, emphasizing both accuracy and interpretability in neuroimaging. Future research will expand to larger, diverse datasets to ensure robustness across varied clinical settings.

Keywords: brain tumor, ensemble learning, explainability, grad-cam, glioma, interpretability, meningioma, multiple sclerosis, pituitary, XAI

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Authors: Lamis Naddaf, Yuval Tabach

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In this research, we identified the missense genetic variants that have the potential to enhance resistance against cancer. Such field has not been widely explored, as researchers tend to investigate mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution, and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and can have significant implications on improved risk estimation, diagnostics, prognosis and even for personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and picked up the alleles that showed a correlation with the species’ cancer resistance. We predicted 250 protecting variants (PVs) with a 0.01 false discovery rate and more than 20 thousand PVs with a 0.25 false discovery rate. Cancer resistance in Mammals and reptiles was significantly predicted by the number of PVs a species has. Moreover, Genes enriched with the protecting variants are enriched in pathways relevant to tumor suppression like pathways of Hedgehog signaling and silencing, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are more abundant in healthy people compared to cancer patients within different human races.

Keywords: comparative genomics, machine learning, cancer resistance, cancer-protecting alleles

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Authors: Hye Jin Kim, Hwa Sung Shin

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Ischemic stroke means the caused brain damage due to neurological defects, occurring occlusion of cerebral vascular resulting in thrombus or embolism. t-PA (tissue Plasminogen Activator) is the only thrombolytic agent passed the FDA (Food and Drug Administration). However, t-PA directly dissolves the thrombus (direct activity) through fibrinolysis, showing side effects such as re-occlusion. In this study, we evaluated the thrombolytic activities of the serine protease extracted from lugworms inhabiting tidal flats. The new serine protease identified as 38 kDa by SDS-PAGE was not toxic to brain endothelial cells line (hCMEC/D3). Also, the plasmin synthesis inhibition activity (indirect activity) of the new serine protease was confirmed through fibrin zymography assay and fibrin plate assay. It was higher than direct activity as compared to u-PA (urokinase Plasminogen Activator). The activities were found to be maintained at a wide range of temperature (4-70 ℃) and pH 7-10 compared to previous thrombolytic agents from the azocasein assay. In addition, the new serine protease has shown anticoagulant activity from fibrinogenolytic activity assay. In conclusion, the serine protease in lug worms inhabiting the tidal flats could be considered a promising thrombolytic candidate for the treatment of ischemic stroke.

Keywords: alkaline serine protease, bifunctional thrombolytic activity, fibrinolytic activity, ischemic stroke, lug worms

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Authors: Nisrine Chlif, Mohammed Diouri, Amar Bentayeb

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Background: The Leaves of Brocchia cinerea (Vis.) (Asteraceae) is used traditionally and ethnomedicinally to alleviate pain, fever, and inflammation conditions. Objective: The current study investigates the anti-inflammatory, analgesic, and antipyretic activities of aqueous extract of the leaves of Brocchia cinerea (LBC). Material and methods: The extract was screened for anti-inflammatory (carrageenan-induced paw edema) and analgesic (acetic acid-induced writhing) activities in Wistar rats. Before acetic acid or carrageenan injection, rats were orally fed LBC (200 and 400 mg/ kg), Indomethacin (10 mg/kg), or Aspirin (100 mg/kg). The antipyretic effect was studied in brewer’s yeast-induced pyrexia model in rats using Paracetamol (100 mg/kg) as a standard drug. Results: The crude extract tested significantly prevented the increase in paw volume as compared to the control at 200 mg/kg and 400 mg/kg. The LBC treatment significantly inhibited pain at 400 mg/kg with a percent inhibition of 55.82%, as well as showing a significant reduction in hyperpyrexia in rats at 400 mg/kg. LBC extract produced a comparable activity to paracetamol at 100 mg/kg (p <0.01). Conclusion: The results of the present study that the leaves of B. cinerea extract exhibited strongly anti-inflammatory, analgesic, and antipyretic properties and justify the traditional use of this plant in inflammation, pain, and fever.

Keywords: analgesic, anti-inflammation, antipyretic, brocchia cinerea

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Authors: H. Yousefnia, S. Zolghadri, A. Golabi Dezfuli

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Tris (1,10-phenanthroline) lanthanum(III)] trithiocyanate is a new compound that has shown to stop DNA synthesis in CCRF-CEM and Ehrlich ascites cells leading to a cell cycle arrest in G0/G1. One other important property of the phenanthroline nucleus is its ability to act as a triplet-state photosensitizer especially in complexes with lanthanides. In Nowadays, the radiation dose assessment resource (RADAR) method is known as the most common method for absorbed dose calculation. 177Lu was produced by irradiation of a natural Lu2O3 target at a thermal neutron flux of approximately 4 × 1013 n/cm2•s. 177Lu-PL3 was prepared in the optimized condition. The radiochemical yield was checked by ITLC method. The biodistribution of the complex was investigated by intravenously injection to wild-type rats via their tail veins. In this study, the absorbed dose of 177Lu-PL3 to human organs was estimated by RADAR method. 177Lu was prepared with a specific activity of 2.6-3 GBq.mg-1 and radionuclide purity of 99.98 %. The 177Lu-PL3 complex can prepare with high radiochemical yield (> 99 %) at optimized conditions. The results show that liver and spleen have received the highest absorbed dose of 1.051 and 0.441 mSv/MBq, respectivley. The absorbed dose values for these two dose-limiting tissues suggest more biological studies special in tumor-bearing animals.

Keywords: internal dosimetry, Lutetium-177, radar, animals

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Authors: Lamis Naddaf, Yuval Tabach

Abstract:

We identified missense genetic variants with the potential to enhance resistance against cancer. Such a field has not been widely explored as researchers tend to investigate the mutations that cause diseases, in response to the suffering of patients, rather than those mutations that protect from them. In conjunction with the genomic revolution and the advances in genetic engineering and synthetic biology, identifying the protective variants will increase the power of genotype-phenotype predictions and have significant implications for improved risk estimation, diagnostics, prognosis, and even personalized therapy and drug discovery. To approach our goal, we systematically investigated the sites of the coding genomes and selected the alleles that showed a correlation with the species’ cancer resistance. Interestingly, we found several amino acids that are more generally preferred (like the Proline) or avoided (like the Cysteine) by the resistant species. Furthermore, Cancer resistance in mammals and reptiles is significantly predicted by the number of the predicted protecting variants (PVs) a species has. Moreover, PVs-enriched-genes are enriched in pathways relevant to tumor suppression. For example, they are enriched in the Hedgehog signaling and silencing pathways, which its improper activation is associated with the most common form of cancer malignancy. We also showed that the PVs are mostly more abundant in healthy people compared to cancer patients within different human races.

Keywords: cancer resistance, protecting variant, naked mole rat, comparative genomics

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Authors: Yousif Mohamed Y. Abdallah

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This is an experimental study deals with detection, measurement and analysis of the periodic physiological organ motion during external beam radiotherapy; to improve the accuracy of the radiation field placement, and to reduce the exposure of healthy tissue during radiation treatments. The importance of this study is to detect the maximum path of the mobile structures during radiotherapy delivery, to define the planning target volume (PTV) and irradiated volume during both inspiration and expiration period and to verify the target volume. In addition to its role to highlight the importance of the application of Intense Guided Radiotherapy (IGRT) methods in the field of radiotherapy. The results showed (body contour was equally (3.17 + 0.23 mm), for left lung displacement reading (2.56 + 0.99 mm) and right lung is (2.42 + 0.77 mm) which the radiation oncologist to take suitable countermeasures in case of significant errors. In addition, the use of the image registration technique for automatic position control is predicted potential motion. The motion ranged between 2.13 mm and 12.2 mm (low and high). In conclusion, individualized assessment of tumor mobility can improve the accuracy of target areas definition in patients undergo Sterostatic RT for stage I, II and III lung cancer (NSCLC). Definition of the target volume based on a single CT scan with a margin of 10 mm is clearly inappropriate.

Keywords: respiratory motion, external beam radiotherapy, image processing, lung

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Authors: Mansi Srivastava, Uzma Saqib, Adnan Naim, Anjali Roy, Dongfang Liu, Deepak Bhatnagar, Ravinder Ravinder, Mirza S. Baig

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Macrophages polarize to proinflammatory M1 or anti-inflammatory M2 states with distinct physiological functions. This transition within the M1 to M2 phenotypes decides the nature, duration, and severity of an inflammatory response. However, inspite of a substantial understanding of the fate of these phenotypes, the underlying molecular mechanisms are not well understood. We have investigated the role of Neuronal nitric oxide synthase (NOS1) mediated regulation of Activator protein 1 (AP-1) transcription factor in macrophages as a critical effector of macrophage phenotypic change. Activator protein 1 (AP-1) is a group of dimeric transcription factors composed of jun, Fos, and ATF family proteins. We determined that NOS1-derived nitric oxide (NO) facilitate Fos and jun interaction which induces IL12 & IL23 expression. Pharmacological inhibition of NOS1 inhibits Fos and jun interaction but increases ATF2 and Fos dimerization. Switching of Fos and jun dimer to ATF2 and jun dimerization switches phenotype from IL–12high IL-23high IL-10low to IL–12low IL-23lowIL-10high phenotype, respectively. Together, these findings highlight a key role of the TLR4-NOS1-AP1 signaling axis in regulating macrophage polarization.

Keywords: inflammation, macrophage, lipopolysaccharide (LPS), proinflammatory cytokines, activator protein 1 (AP-1), neuronal nitric oxide synthase (NOS1)

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Authors: Omar M. Al Aufi, Abdulwahab Noorwali, Ahmed Al Abd, Safia Alattas, Fathya Zahran, Fahd Almutairi

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Cisplatin (CDDP) is a potent anticancer agent used for several tumor types. Thymoquinone (TQ) is a naturally occurring compound drawing great attention as an anticancer and chemomodulator for chemotherapies. Herein, we studied the potential cytotoxicity of thymoquinone, CDDP and their combination against human oral squamous cell carcinoma cells in contrast to normal oral epithelial cells. CDDP similarly killed both head and neck squamous cell carcinoma cells (UMSCC-14C) and normal oral epithelial cells (OEC). TQ alone exerted considerable cytotoxicity against UMSCC-14C cells, while it induced a weaker killing effect against normal oral epithelial cells (OEC). The equitoxic combination of TQ and CDDP showed additive to synergistic interaction against both UMSCC-14C and OEC cells. TQ alone increased apoptotic cell fraction in UMSCC-14C cells as early as after 6 hours. In addition, prolonged exposure of UMSCC-14C to TQ alone resulted in 96.7±1.6% total apoptosis, which was increased after combination with CDDP to 99.3±1.2% in UMSCC-14C cells. On the other hand, TQ induced a marginal increase in the apoptosis in OEC and even decreased the apoptosis induced by CDDP alone. Finally, apoptosis induction results were confirmed by the change in the expression levels of p53, Bcl-2 and Caspase-9 proteins in both UMSCC-14c and OEC cells.

Keywords: thymoquinone, cisplatin, apoptosis, oral squamous cell carcinoma, P53, Caspase-9, Bcl-2

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Authors: Isa Shu’aibu, A. A. Mu’inat, F. U. Maigari, M. A. Mani

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Candida albicans is the common cause of both oral and vaginal candidiasis in humans. This candidiasis leads to a wide range of physical, psychological and even physiological problems in humans particularly pregnant women. Samples of endocervical and high vaginal swab were collected from 200 women attending Gombe Specialist Hospital and inoculated on Saboraud Dextrose Agar (SDA) incorporated with chloramphenicol to get rid of the unwanted bacterial contaminants. Gram staining technique and germ tube test were employed for the identification, as Candida albicans is positive for both. Gram positive samples were 70% (n=140) and were further subjected to germ tube test. The remaining 30% (n=60) were found to be Gram negative. 90% (n=126) of the Gram positive ones isolated were also found to be positive for germ tube test; confirming the presence of Candida albicans. Antifungal susceptibility testing revealed that members of Imidazole (Ketoconazole, Miconazole) and those of Triazoles (Fluconazole and Itraconazole) were found to be more effective at concentrations of 20, 50 and 100 µg/disc compared to Griseofulvin (Fulcin) with only 26.00 mm zone of inhibition at 100 µg/disc concentration.

Keywords: Candida albicans, candidiasis, endocervical, vaginal swab, antifungal susceptibility, imidazole, triazoles

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Authors: Madhumita Sahu, S. S. Tiwary

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The Radiotherapy of Carcinoma Lung has always been difficult and a matter of great concern. The significant movement due to fractional motion caused due to non-rhythmic respiratory motion poses a great challenge for the treatment of Lung cancer using Ionizing Radiation. The present study compares the accuracy in the measurement of Target Volume using Slow-CT and 4DCT Imaging in SBRT for Lung Tumor. The experimental samples were extracted from patients with Lung Cancer who underwent SBRT. Slow-CT and 4DCT images were acquired under free breathing for each patient. PTV were delineated on Slow CT images. Similarly, ITV was also delineated on each of the 4DCT volumes. Volumetric and Statistical analysis were performed for each patient by measuring corresponding PTV and ITV volumes. The study showed (1) The Maximum Deviation observed between Slow-CT-based PTV and 4DCT imaging-based ITV is 248.58 cc. (2) The Minimum Deviation observed between Slow-CT-based PTV and 4DCT imaging-based ITV is 5.22 cc. (3) The Mean Deviation observed between Slow-CT-based PTV and 4DCT imaging-based ITV is 63.21 cc. The present study concludes that irradiated volume ITV with 4DCT is less as compared to the PTV with Slow-CT. A better and more precise treatment could be given more accurately with 4DCT Imaging by sparing 63.21 CC of mean body volume.

Keywords: CT imaging, 4DCT imaging, lung cancer, statistical analysis

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Authors: Salem Abdalla

Abstract:

Objective: Dipyrone is a widely used, well tolerated analgesic drug which, however, is compromised by agranulocytosis as an adverse effect. Subsequent to no enzymatic hydrolysis, the primary metabolic step is N-demethylation of 4-methylaminoantipyrine (4-MAA) to 4-aminoantipyrine (4-AA). The aim of the present study was to identify the cytochrome P-450 enzyme (CYP) mediating this reaction. Methods: We identified the relevant CYP using virus expressed isolated rat liver microsomes with chemical inhibition studies. The substrate of 4-methylaminantipyrine was employed at six different concentrations (25, 50, 100, 400, 800, and 1200 µmol/l) with varying concentrations of selective inhibitors of CYP1A2 (furafylline, fluvoxamine), CYP3A4 (ketoconazole), CYP2A6 (coumarin), CYP2D6 (quinidine), CYP2C19 (omeprazole, fluvoxamine, tranylcypromine), CYP2C9 (sulfaphenazole), and CYP1A1 (alpha-naphthoflavone). 4-MAA and 4-AA were analyzed by HPLC, and enzyme kinetic parameters (Km and Vmax) were determined by regression (Sigma plot 9.0). Results: The N-demethylation of 4-MAA by microsomes prepared from baculovirus-expressing human CYP was pronounced with CYP2C19. Intrinsic clearances of the most active enzymes were 0.092, 0.027, and 0.026 for the CYP enzymes 2C19, 2D6, and 1A2, respectively. Metabolism by rat liver microsomes was strongly inhibited by omeprazole (IC50 of 0.05). Conclusion: The enzyme CYP2C19 apparently has an important role in N-demethylation of 4-methylaminoantipyrine which should be further analyzed in clinical studies and which may also be interesting concerning the agranulocytosis.

Keywords: dipyrone, 4-methylaminoantipyrine (4-MAA), 4- aminoantipyrine (4-AA), metabolism, human CYP2C19

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Authors: Ahmad Shanei, Milad Baradaran-Ghahfarokhi

Abstract:

This study aimed to investigate testicular dose (TD) and the associated risk of heritable disease from common pelvis radiotherapy of male patients in Iran. In this work, the relation between TD and changes in beam energy, pelvis size, source to skin distance (SSD) and beam directions (anterior or posterior) were also evaluated. The values of TDs were measured on 67 randomly selected male patients during common pelvis radiotherapy using 1.17 and 1.33 MeV, Theratron Cobalt-60 unit at SSD of 80 cm and 9 MV, Neptun 10 PC and 18 MV, GE Saturne 20 at SSD of 100 cm at Seyed-Al Shohada Hospital, Isfahan, Iran. Results showed that the maximum TD was up to 12% of the tumor dose. Considering the risk factor for radiation-induced heritable disorders of 0.1% per Sv, an excess risk of hereditary disorders of 72 per 10000 births was conservatively calculated. There was a significant difference in the measured TD using different treatment machines and energies (P < 0.001). The TD at 100 cm SSD were much less than that for 80 cm SSD (P <0.001). The Pearson Correlation test showed that, as expected, there was a strong correlation between TD and patient’s pelvis size (r = 0.275, P <0.001). Using the student’s t-tests, it was found that, there was not a significant difference between TD and beam direction (P = 0.231). Iranian male patients undergoing pelvic radiotherapy have the potential of receiving a TD of more than 1 Gy which might result in temporary azoospermia. The risk for induction of hereditary disorders in future generations should be considered as low but not negligible in comparison with the correspondent nominal risk.

Keywords: pelvis radiotherapy, testicular dose, infertility, hereditary effects

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Authors: Srisopa Ruangnoo, Arunporn Itharat

Abstract:

The ethanolic and aqueous extracts of Parkia javanica Merr. germinating seeds and Parkia speciosa Hassk. seeds were evaluated for cytotoxic activity against three different types of human cancer cell lines including colon cancer (LS174T), breast cancer (MCF-7) and prostate cancer (PC3) using sulforhodamine B (SRB) assay. The fresh plant parts were divided into 2 parts. The first part was extracted by maceration with 95% ethanol for 3 days and then filtered, and the filtrates were evaporated by rotary evaporator. The other part was squeezed and filtered. Then the filtrates were dried by freeze dryer. The screening found that the aqueous extract of P. javanica Merr. germinating seeds exhibited more than 70% inhibition (at concentration 50 µg/ml) against all types of human cancer cells. The aqueous extract of P. javanica Merr. germinating seeds showed the highest cytotoxic activity against MCF-7 with the IC50 value as 5.63 µg/ml. The aqueous extract of P. javanica Merr. germinating seeds also showed high cytotoxic activity against PC3 and LS174T with the IC50 values as 10.79 and 11.40 µg/ml, respectively. In conclusion, P. javanica Merr. germinating seed is a natural source of anticancer activity and further research to isolate active compounds from this plant should be undertaken.

Keywords: cytotoxic activity, Parkia javanica Merr., Parkia speciosa Hassk., human cancer cell lines

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Authors: Shuafeng Yuan, Bojian Zheng

Abstract:

The RNA-dependent RNA polymerase of influenza a virus comprises conserved and independently folded subdomains with defined functionalities. The N-terminal domain of the PA subunit (PAN) harbors the endonuclease function so that it can serve as a desired target for drug discovery. To identify a class of anti-influenza inhibitors that impedes PAN endonuclease activity, a screening approach that integrated the fluorescence resonance energy transfer based endonuclease inhibitor assay with the DNA gel-based endonuclease inhibitor assay was conducted, followed by the evaluation of antiviral efficacies and potential cytotoxicity of the primary hits in vitro and in vivo. A small-molecule compound ANA-0 was identified as a potent inhibitor against the replication of multiple subtypes of influenza A virus, including H1N1, H3N2, H5N1, H7N7, H7N9 and H9N2, in cell cultures. Combinational treatment of zanamivir and ANA-0 exerted synergistic anti-influenza effect in vitro. Intranasal administration of ANA-0 protected mice from lethal challenge and reduced lung viral loads in H1N1 virus infected BALB/c mice. Docking analyses predicted ANA-0 bound the endonuclease cavity of PAN by interacting with the metal-binding and catalytic residues. In summary, ANA-0 shows potential to be developed to novel anti-influenza agents.

Keywords: anti-influenza, novel compound, inhibition of endonuclease, PA

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Authors: Yu-Chih Wang, Chia-Yu Lai, Hsiao-Tien Liu, Yi-Ju Chen, Shao-Bin Cheng

Abstract:

Liver transplant has been one of the curative treatment options for hepatocellular carcinomaunder certain oncological conditions. Two of the most validated criteria are from Milan in1996 and USCF in 2001, suggesting number and size limits of tumor without vascularinvasion or distant metastasis. We performed a retrospective cohort study of hepatocellular carcinoma patients undergoing livertransplant between August 2003 and December 2020 in our institute. Clinical andpathological characteristic, survival outcome, and recurrent pattern were analysed.UCSF criteria was applied for living donor transplantation, and Milan criteria was applied for deceased donor transplantation. Of 180 total patients, 52 cases(28.8%) with diagnosis of hepatocellular carcinoma, including26 living donor(LD) and 26 deceased donor(DD) liver transplant. Complete pathologicalremission was significantly more in the DD group(p=0.009). Pathological reports showed that30.8% of DD group exceeded Milan criteria, and 19.2% of LD group exceeded UCSFcriteria.After a median follow-up of 52.2 months, the 1-year, 3-year and 5-year overall survival was 87.6%, 74.1%, and 71.8%, respectively.Meanwhile, progression-free survival was 93.1%, 85.7%, and 81.6% for 1, 3, and 5-year, respectively, similar to that in Mazzaferro et al, 1996. We concluded that Liver transplant could be applied cautiously in expanded criteria for patent withhepatocellular carcinoma.

Keywords: liver transplant, milan criteria, UCSF criteria, living donor transplantation, deceased donor transplantation

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Authors: Kave Moloudi, Heidi Abrahamse, Blassan P. George

Abstract:

Radiotherapy (RT) and photodynamic therapy (PDT) are both forms of cancer treatment that aim to kill cancer cells while minimizing damage to healthy tissue. The similarity between RT and PDT lies in their mechanism of action. Both treatments use energy to damage cancer cells. RT uses high-energy radiation to damage the DNA of cancer cells, while PDT uses light energy to activate a photosensitizing agent, which produces reactive oxygen species (ROS) that damage the cancer cells. Both treatments require careful planning and monitoring to ensure the correct dose is delivered to the tumor while minimizing damage to surrounding healthy tissue. They are also often used in combination with other treatments, such as surgery or chemotherapy, to improve overall outcomes. However, there are also significant differences between RT and PDT. For example, RT is a non-invasive treatment that can be delivered externally or internally, while PDT requires the injection of a photosensitizing agent and the use of a specialized light source to activate it. Additionally, the side effects and risks associated with each treatment can vary. In this review, we focus on generalizing the 6Rs of radiobiology in PDT, which can open a window for the clinical application of Radio-photodynamic therapy with minimum side effects. Furthermore, this review can open new insight to work on and design new radio-photosensitizer agents in Radio-photodynamic therapy.

Keywords: radiobiology, photodynamic therapy, radiotherapy, 6Rs in radiobiology, ROS, DNA damages, cellular and molecular mechanism, clinical application.

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Authors: Sungging Pintowantoro, Yuli Setiyorini, Rochman Rochim, Agung Purniawan

Abstract:

The bacterial infections are frequent and undesired occurrences after bone fracture treatment. One approach to reduce the incidence of bone fracture infection is the additional of microbial agents into bone cement. In this study, the synthesis of bone cement from re-cycles biowaste was successfully conducted completed with anti-bacterial function. The re-cycle of biowaste using microwave assisted was done in our previous studies in order to produce some of powder (calcium carbonate, carbonated-hydroxyapatite and chitosan). The ratio of these powder combined with methylmethacrylate (MMA) as the matrix in bone cement were investigated using XRD, FTIR, SEM-EDX, hardness test and anti-bacterial test, respectively. From the XRD, FTIR and EDX were resulted the formation of carbonated-hydroxyapatite, calcium carbonate and chitosan. The morphology was revealed porous structure both C2H3K1L and C2H1K3L, respectively. The antibacterial activity was tested against Staphylococcus aureus (S. aureus) for 24 hours. The inhibition of S. aureus was clearly shown, the hollow zone was resulted in various distance 14.2mm, 7.5mm, and 7.7mm, respectively. The hardness test was depicted in various results, however, C2H1K3L can be achived 36.84HV which is closed to dry cancelous bone 35HV. In general, this study results was promising materials to use as bone cement materials.

Keywords: biomaterials, biowaste recycling, materials processing, microwave processing

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Authors: A. V. Belousov, Yakushenko

Abstract:

One of the main problems of modern dentistry is development a reliable method to detect inflammation in the gums on the stages of diagnosis and assessment of treatment efficacy. We have proposed a method of gingival fluid intake, which successfully combines accessibility, excluding the impact of the annoying and damaging the gingival sulcus factors and provides reliable results (patent of RF№ 2342956 Method of gingival fluid intake). The objects of the study were students - volunteers of Dentistry Faculty numbering 75 people aged 20-21 years. Cellular composition of gingival fluid was studied using microscope "Olympus CX 31" (Japan) with the calculation of epithelial leukocyte index (ELI). Assessment of gingival micro circulation was performed using the apparatus «LAKK–01» (Lazma, Moscow). Cytological investigation noted the highly informative of epithelial leukocyte index (ELI), which demonstrated changes in the mechanisms of protection gums. The increase of ELI occurs during inhibition mechanisms of phagocytosis and activation of epithelial desquamation. The cytological data correlate with micro circulation indicators obtained by laser Doppler flowmetry. We have identified and confirmed the correlations between parameters laser Doppler flowmetry and data cytology gingival fluid in patients with gingivitis.

Keywords: gingivitis, laser doppler flowmetry, gingival fluid cytology, epithelial leukocyte index (ELI)

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