Search results for: metastatic squamous cell carcinoma

Authors: Farhad Forouharmajd, Hossein Ebrahimi, Siamak Pourabdian

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Introduction: Prevalent use of cell phones (mobile phones) has led to increasing worries about the effect of radiofrequency waves on the physiology of human body. This study was done to determine different reactions of the temperatures in different depths of brain tissue in confronting with radiofrequency waves of cell phones. Methodology: This study was an empirical research. A cow's brain tissue was placed in a compartment and the effects of radiofrequency waves of the cell phone was analyzed during confrontation and after confrontation, in three different depths of 2, 12, and 22 mm of the tissue, in 4 mm and 4 cm distances of the tissue to a cell phone, for 15 min. Lutron thermometer was used to measure the tissue temperatures. Data analysis was done by Lutron software. Findings: The rate of increasing the temperature at the depth of 22 mm was higher than 2 mm and 12mm depths, during confrontation of the brain tissue at the distance of 4 mm with the cell phone, such that the tissue temperatures at 2, 12, and 22 mm depths increased by 0.29 ˚C, 0.31 ˚C, and 0.37 ˚C, respectively, relative to the base temperature (tissue temperature before confrontation). Moreover, the temperature of brain tissue at the distance of 4 cm by increasing the tissue depth was more than other depths. Increasing the tissue temperature also existed by increasing the brain tissue depth after the confrontation with the cell phone. The temperature of the 22 mm depth increased with higher speed at the time confrontation. Conclusion: Not only radiofrequency waves of cell phones increased the tissue temperature in all the depths of the brain tissue, but also the temperature due to radiofrequency waves of the cell phone was more at the depths higher than 22 mm of the tissue. In fact, the thermal effect of radiofrequency waves was higher in higher depths.

Keywords: mobile phone, radio frequency waves, brain tissue, temperature

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Authors: Susanne Fridsten, Kristina Hellman, Anders Sundin, Lennart Blomqvist

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Background: Patients diagnosed with locally advanced cervical carcinoma are treated with definitive concomitant chemo-radiotherapy. Treatment failure occurs in 30-50% of patients with very poor prognoses. The treatment is standardized with risk for both over-and undertreatment. Consequently, there is a great need for biomarkers able to predict therapy outcomes to allow for individualized treatment. Aim: To explore the role of T2- and diffusion-weighted magnetic resonance imaging (MRI) for early prediction of therapy outcome and the optimal time point for assessment. Methods: A pilot study including 15 patients with cervical carcinoma stage IIB-IIIB (FIGO 2009) undergoing definitive chemoradiotherapy. All patients underwent MRI four times, at baseline, 3 weeks, 5 weeks, and 12 weeks after treatment started. Tumour size, size change (∆size), visibility on diffusion-weighted imaging (DWI), apparent diffusion coefficient (ADC) and change of ADC (∆ADC) at the different time points were recorded. Results: 7/15 patients relapsed during the study period, referred to as "poor prognosis", PP, and the remaining eight patients are referred to "good prognosis", GP. The tumor size was larger at all time points for PP than for GP. The ∆size between any of the four-time points was the same for PP and GP patients. The sensitivity and specificity to predict prognostic group depending on a remaining tumor on DWI were highest at 5 weeks and 83% (5/6) and 63% (5/8), respectively. The combination of tumor size at baseline and remaining tumor on DWI at 5 weeks in ROC analysis reached an area under the curve (AUC) of 0.83. After 12 weeks, no remaining tumor was seen on DWI among patients with GP, as opposed to 2/7 PP patients. Adding ADC to the tumor size measurements did not improve the predictive value at any time point. Conclusion: A large tumor at baseline MRI combined with a remaining tumor on DWI at 5 weeks predicted a poor prognosis.

Keywords: chemoradiotherapy, diffusion-weighted imaging, magnetic resonance imaging, uterine cervical carcinoma

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Authors: Mazouz Halima, Belghachi Abdrahmane

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Effects of electron irradiation-induced deep level defects have been studied on both n/p and p/n indium phosphide solar cells with very thin emitters. The simulation results show that n/p structure offers a somewhat better short circuit current but the p/n structure offers improved circuit voltage, not only before electron irradiation, but also after 1MeV electron irradiation with 5.1015 fluence. The simulation also shows that n/p solar cell structure is more resistant than that of p/n structure.

Keywords: InP solar cell, p/n and n/p structure, electron irradiation, output parameters

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Authors: Marin Kanarev, Delyan Stoyanov, Ivanna Popova, Nadezhda Petrova

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Thanks to increased survival rates in patients bearing oncological malignancies due to recent developments in anti-cancer therapies and diagnostic techniques, observation of clinical cases of metachronous cancers is more common and can provide more in-depth knowledge of their development and, as a result, help clinicians apply suitable therapy. This unusual case of three metachronous tumors presented the opportunity to follow their occurrence, progression, and treatment thoroughly. A 77-year-old male presented with carcinoma ventriculi of the pylorus region, which was surgically removed via upper subtotal stomach resection, a lateral antecolical gastro-enteroanastomosis, and a subsequent Braun anastomosis. An EOX chemotherapy regimen followed. A CT scan four months later showed no indication of recurrence or dissemination. The same scan, performed as a part of the follow-up plan two years later, showed an indication of neoplastic growth in the urinary bladder. After the patient had been directed to a urologist, the suspicion was confirmed, and the growth was histologically diagnosed as a carcinoma of the urinary bladder. An immunohistochemistry test showed an expression of PDL1 of less than 5%, which resulted in treatment with GemCis chemotherapy regimen that led to full remission. Two years and seven months after the first surgery, a CT scan showed again that the two carcinomas were gone. However, four months later, elevated tumor markers prompted a PET/CT scan, which showed data indicative of recurring neoplastic growth in the region of the stomach cardia. It was diagnosed as an adenocarcinoma infiltrating the esophagus. Preoperative chemotherapy with the ECF regimen was completed in four courses, and a CT scan showed no progression of the disease. In less than a month after therapy, the patient underwent laparotomy, debridement, gastrectomy, and a subsequent mechanical terminal-lateral esophago-jejunoanasthomosis. It was verified that the tumor originated from metastasis from the carcinoma ventriculi, which was located in the pylorus. In conclusion, this case report highlights the importance of patient follow-up and studying recurring neoplastic growth. Despite the absence of symptoms, clinicians should maintain a high level of suspicion when evaluating the patient data and choosing the most suitable therapy.

Keywords: carcinoma, follow-up, metachronous, neoplastic growth, recurrence

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Authors: L. Korpinen, R. Pääkkönen, F. Gobba

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Accidents and close call situations involving cell phones are nowadays possible. The objective of this study was to investigate the accidents and close call situations due to cell phone use while moving, driving, and working among Finns aged between 18 and 65. This work is part of a large cross-sectional study that was carried out on 15,000 working-age Finns. About 26% of people who had an accident, and about half of the people including close call situation with the mobile phone, answered that use of the phone influenced. In the future, it is important to take into account that the use of a mobile phone can be distracting while driving.

Keywords: blue-collar workers, accident, cell phone, close call situation

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Authors: Mohamad F. Jamiluddin, Emeline Sarry, Ana Bejanariu, Cécile Bauche

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Introduction: Over 360 million people are chronically infected with hepatitis B virus (HBV), of whom 1 million die each year from HBV-associated liver cirrhosis or hepatocellular carcinoma. Current treatment options for chronic hepatitis B depend on interferon-α (IFNα) or nucleos(t)ide analogs, which control virus replication but rarely eliminate the virus. Treatment with PEG-IFNα leads to a sustained antiviral response in only one third of patients. After withdrawal of the drugs, the rebound of viremia is observed in the majority of patients. Furthermore, the long-term treatment is subsequently associated with the appearance of drug resistant HBV strains that is often the cause of the therapy failure. Among the new therapeutic avenues being developed, therapeutic vaccine aimed at inducing immune responses similar to those found in resolvers is of growing interest. The high prevalence of chronic hepatitis B necessitates the design of better vaccination strategies capable of eliciting broad-spectrum of cell-mediated immunity(CMI) and humoral immune response that can control chronic hepatitis B. Induction of HBV-specific T cells and B cells by therapeutic vaccination may be an innovative strategy to overcome virus persistence. Lentiviral vectors developed and optimized by THERAVECTYS, due to their ability to transduce non-dividing cells, including dendritic cells, and induce CMI response, have demonstrated their effectiveness as vaccination tools. Method: To develop a HBV therapeutic vaccine that can induce a broad but specific immune response, we generated recombinant lentiviral vector carrying IRES(Internal Ribosome Entry Site)-containing bicistronic constructs which allow the coexpression of two vaccine products, namely HBV T- cell epitope vaccine and HBV virus like particle (VLP) vaccine. HBV T-cell epitope vaccine consists of immunodominant cluster of CD4 and CD8 epitopes with spacer in between them and epitopes are derived from HBV surface protein, HBV core, HBV X and polymerase. While HBV VLP vaccine is a HBV core protein based chimeric VLP with surface protein B-cell epitopes displayed. In order to evaluate the immunogenicity, mice were immunized with lentiviral constructs by intramuscular injection. The T cell and antibody immune responses of the two vaccine products were analyzed using IFN-γ ELISpot assay and ELISA respectively to quantify the adaptive response to HBV antigens. Results: Following a single administration in mice, lentiviral construct elicited robust antigen-specific IFN-γ responses to the encoded antigens. The HBV T- cell epitope vaccine demonstrated significantly higher T cell immunogenicity than HBV VLP vaccine. Importantly, we demonstrated by ELISA that antibodies are induced against both HBV surface protein and HBV core protein when mice injected with vaccine construct (p < 0.05). Conclusion: Our results highlight that THERAVECTYS lentiviral vectors may represent a powerful platform for immunization strategy against chronic hepatitis B. Our data suggests the likely importance of Lentiviral vector based novel bicistronic construct for further study, in combination with drugs or as standalone antigens, as a therapeutic lentiviral based HBV vaccines. THERAVECTYS bicistronic HBV vaccine will be further evaluated in animal efficacy studies.

Keywords: chronic hepatitis B, lentiviral vectors, therapeutic vaccine, virus-like particle

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Authors: Ana Paula Rosifini Alves Claro, André Luiz Reis Rangel, Nathan Trujillo, Ketul C. Popat

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In the present work, in vitro cytotoxicity was evaluated after nanotubes growth on Ti15Mo alloy surface. TiO2 nanotubes were obtained by anodizing technique at room temperature in an electrolyte with 0.25 %NH4F and glycerol at a constant anodic potential of 20 V for 24 hours. The morphology of nanotubes was observed by field emission scanning electron microscopy (FE-SEM; XL 30 FEG, Philips). Crystal structure was analyzed by wide-angle X-ray diffraction. A cell culture model using human fibroblast-like cells was used to study the effect of TiO2 nanotubes growth on the cytotoxicity of the Ti15Mo alloy for 1, 4 and 7 days culture period. The MTT assay was used to evaluate cell viability and cell adhesion was evaluated by scanning electron microscopy. Results show that Ti15Mo alloy with TiO2 nanotubes on surface is nontoxic and exhibit good interaction with surface.

Keywords: titanium alloys, TiO2 nanotubes, cell growth, Ti-15Mo alloy

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Authors: Shikha Masand, Sudesh Kumar Yadav

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Certain protein kinases have been shown to be crucial for plant cell signaling pathways associated with plant immune responses. Here we identified a horsegram [Macrotyloma uniflorum (Lam.) Verdc.] malectin-like leucine rich receptor-like protein kinase (RLK) gene MuRLK. The functional MuRLK protein preferentially binds to mannose and N-acetyl glucosamine residues. MuRLK exists in the cytoplasm and also localizes to the plasma membrane of plant cells via its N-terminus. Over-expression of MuRLK in Arabidopsis enhances the basal resistance to infection with Pseudomonas syringae pv. tomato, Alternaria brassicicola and Hyaloperonospora arabidopsidis, are associated with elevated ROS bursts, MAPK activation, thus ultimately leading to hypersensitive cell death. Moreover, salicylic acid-dependent and jasmonic acid-dependent defense responses are also enhanced in the MuRLK-overexpressed plants that lead to HR-induced cell death. Together, these results suggest that MuRLK plays a key role in the regulation of plant cell death, early and late defense responses after the recognition of microbial pathogens.

Keywords: horsegram, Pseudomonas syringae pv. tomato, MuRLK, ROS burst, cell death, plant defense

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Authors: Emrah Ersoy, Yusuf Ozcatalbas

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The aim of this study is to investigate formability of Al based closed cell metallic foams at high temperature. The foam specimens with rectangular section were produced from AlMg1Si0.6TiH20.8 alloy preform material. Bending and free bending tests based on gravity effect were applied to foam specimens at high temperatures. During the tests, the time-angular deformation relationships with various temperatures were determined. Deformation types formed in cell walls were investigated by means of Scanning Electron Microscopy (SEM) and optical microscopy. Bending deformation about 90° was achieved without any defect at high temperatures. The importance of a critical temperature and deformation rate was emphasized in maintaining the deformation. Significant slip lines on surface of cell walls at tensile zones of bending specimen were observed. At high strain rates, the microcrack formation in boundaries of elongated grains was determined.

Keywords: Al alloy, Closed cell, Hot deformation, Metallic foam

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Authors: Sana Abbasa, Shahzad Bhattiab, Nadir Khan

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Sargassum siliquastrum is brown seaweed with traditional claims for some medicinal properties. This research was done to investigate the methanol extract of S. siliquastrum for antiproliferative activity against human cervical cancer cell line, HeLa and its mode of cell death. From methylene blue assay, S. siliquastrum exhibited antiproliferative activity on HeLa cells with IC50 of 3.87 µg/ml without affecting non-malignant cells. Phase contrast microscopy indicated the confluency reduction in HeLa cells and changes on the cell shape. Nuclear staining with Hoechst 33258 displayed the formation of apoptotic bodies and fragmented nuclei. S. siliquastrum also induced early apoptosis event in HeLa cells as confirmed by FITC-Annexin V/propidium iodide staining by flow cytometry analysis. Cell cycle analysis indicated growth arrest of HeLa cells at G1/S phase. Protein study by flow cytometry indicated the increment of p53, slight increase of Bax and unchanged level of Bcl-2. In conclusion, S. siliquastrum demonstrated an antiproliferative activity in HeLa cell by inducing G1/S cell cycle arrest via p53-mediated pathway.

Keywords: sargassum siliquastrum, cervical cancer, P53, antiproleferation

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Authors: Drashti G. Daraji, Rosa E. Moo-Puc, Hitesh D. Patel

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Substituted 2-Thioimidazole analogues have been synthesized and confirmed by advanced spectroscopic techniques. Among them, ten compounds have been selected and evaluated for their in vitro anti-cancer activity at the National Cancer Institute (NCI) for testing against a panel of 60 different human tumor cell lines derived from nine neoplastic cancer types. Furthermore, synthesized compounds were tested for their in vitro antiprotozoal activity, and none of them exhibited significant potency against antiprotozoans. It was observed that the tested all compounds seem effective on the UACC-62 melanoma cancer cell line as compared to other cancer cell lines and also exhibited the least potent in the Non-Small Cell Lung Cancer cell line in one-dose screening. In silico studies of these derivatives were carried out by molecular docking techniques and Absorption, Distribution, Metabolism, and Excretion (ADME) using Schrödinger software to find potent B-Raf kinase inhibitor (PDB ID: 3OG7). All the compounds have been performed for docking study; Compound D4 has a good docking score for melanoma cancer as compared with other.

Keywords: anticancer activity, cancer cell line, 2-thio imidazole, one-dose assay, molecular docking

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Authors: Soroosh Torabi, Brad Berron, Ren Xu, Christine Trinkle

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Microfluidics integrated with 3D cell culture is a powerful technology to mimic cellular environment, and can be used to study cell activities such as proliferation, migration and response to drugs. This technology has gained more attention in cancer studies over the past years, and many organ-on-a-chip systems have been developed to study cancer cell behaviors in an ex-vivo tumor microenvironment. However, there are still some barriers to adoption which include low throughput, complexity in 3D cell culture integration and limitations on non-optical analysis of cells. In this study, a user-friendly microfluidic multi-well plate was developed to mimic the in vivo tumor microenvironment. The microfluidic platform feeds multiple 3D cell culture sites at the same time which enhances the throughput of the system. The platform uses hydrophobic Cassie-Baxter surfaces created by microchannels to enable convenient loading of hydrogel/cell suspensions into the device, while providing barrier free placement of the hydrogel and cells adjacent to the fluidic path. The microchannels support convective flow and diffusion of nutrients to the cells and a removable lid is used to enable further chemical and physiological analysis on the cells. Different breast cancer cell lines were cultured in the device and then monitored to characterize nutrient delivery to the cells as well as cell invasion and proliferation. In addition, the drug response of breast cancer cell lines cultured in the device was compared to the response in xenograft models to the same drugs to analyze relevance of this platform for use in future drug-response studies.

Keywords: microfluidics, multi-well 3d cell culture, tumor microenvironment, tumor-on-a-chip

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Authors: Chi-Jung Chung, Chao-Hsiang Chang, Chiu-Shong Liu, Sheng-Wei Li, Mu-Chi Chung, Ting-Jie Wen, Hui-Ling Lee

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Cigarette smoke contains volatile organic compounds (VOCs), such as acrylamide, 1,3-butadiene, and benzene. This study aimed to explore the associations between the urinary levels of cotinine and VOC metabolites and the risk of urothelial carcinoma (UC). A hospital-based case–control study involving two groups matched on the basis of age ( ± 3 years) and gender was designed. UC was clinically diagnosed through urological examinations and pathologically verified. Smoking-related information was collected through questionnaires and face-to-face interviews with all study participants. Urine samples were collected for the analysis of the urinary levels of VOC metabolites, cotinine, and 8-hydroxydeoxygua- nosine (8-OHdG), which was selected as a proxy of oxidative stress. Multiple logistic regressions were applied to estimate the risk of UC. The urinary cotinine and 8-OHdG levels of the UC group were higher than those of the control group. The urinary levels of VOC metabolites, including N-acetyl-S-(2-carbamoylethyl)-L-cysteine (AAMA), N- acetyl-S-(2-carbamoyl-2-hydroxyethyl)-L-cysteine, N-acetyl-S- (4- hydroxy-2-buten-1-yl)-Lcysteine-3, trans, trans-muconic acid (t,t- MA), and S-phenylmercapturic acid (SPMA) increased as the urinary levels of cotinine increased. Relevant dose-response relationships between the risk of UC risk and the urinary levels of AAMA , t,t-MA, SPMA, and 8-OHdG were found after adjusting for potential risk factors. The UC risk of participants with high urinary levels of cotinine, AAMA, t,t-MA, SPMA, and 8-OHdG were 3.5–6-fold higher than those of other participants. Increased urinary levels of VOC metabolites were associated with smoking-related UC risk. The development of UC should be explored in large-scale in vitro or in vivo studies with the repeated measurement of VOC metabolites.

Keywords: volatile organic compound, urothelial carcinoma, cotinine, 8-hydroxydeoxyguanosine

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Authors: Remzi Şahin, Sadık Ata, Kevser Dincer

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In this study, performance of proton exchange membrane (PEM) fuel cell was experimentally investigated. The efficiency of energy conversion in PEM fuel cells is dependent on the catalytic activities of the catalysts used in the cathode and anode of membrane electrode assemblies. Membrane is considered the heart of PEM fuel cells without which they cannot produce electricity. PEM fuel cell performance increased with coating carbon nanotube (CNT). CNT show a unique combination of stiffness, strength, and tenacity compared to other fiber materials which usually lack one or more of these properties. Two different experiments were performed and the membrane performance has been determined by repeating the two experiments that were done before coating. The purposes of these experiments are the observation of power change due to a temperature change in the same voltage value.

Keywords: carbon nanotube (CNT), proton exchange membrane (PEM), fuel cell, spin method

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Authors: Mahfoodha Al-Kitani, Dylan Thompson, Keith Stokes

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Sickle cell disease (SCD) and sickle cell trait (SCT) are the most common hematological diseases in Oman according to the national survey of genetic blood disorders. The aim of this study was to determine markers of physical fitness and anthropometrics indices in children with sickle cell disease and children with sickle cell trait and compare them with normal healthy children of the same age. One hundred and twenty male children participated in the present study divided to three groups: 40 with sickle disease (SCD; age, 13.3(.80), height, 131.9(3.5), mass, 29.2(3.1)); 40 with sickle cell trait (SCT; age, 12.2(.80), height, 141.0(9.9), mass, 38.0(4.4)); and 40 controls with normal hemoglobin (Con; age, 12.8(.80), height, 139.4(8.7), mass, 37.2(4.3)). All children completed a 5-min running exercise test on a treadmill at speed corresponding to 5 km/hr. Heart rate and was recorded during exercise and during 10-min of recovery. Blood lactate was measured before and 5 min after the completion of exercise. Children with SCD exhibited a higher mean value (P < 0.05) for percent body fat and fat mass than the normal healthy subjects and SCT subjects. Resting values of hemoglobin were similar in SCT (11.04(.78)) and control (10.8(94)) groups, and lower in SCD (8.89(.54); P < 0.05). There was a strong correlation between peak heart rate and resting hemoglobin levels for the three groups (r= -.472. n= 120, p < .0005).The SCD group (175.2(10.3)) exhibited higher mean heart rate during exercise than those observed in the SCT (143.7(9.5)) and normal control children (144.5(22.4); P < 0.05). Additionally, SCD children showed higher serum lactate values before and after treadmill exercise compared to the other groups (P < 0.05). Children with sickle cell trait demonstrate similar physical fitness level and similar exercise responses to treadmill stress test to normal children. In contrast, SCD children have lower body mass, higher fat mass and lower physical fitness than children with SCT and healthy controls.

Keywords: sickle cell disease, sickle cell trait, children, exercise

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Authors: Tan Yong Sheng Edgar, Yeong Wai Yee

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Age-related macular degeneration (AMD) is one of the leading cause of blindness. It can cause severe visual loss due to damaged retinal pigment epithelium (RPE). RPE is an important component of the retinal tissue. It functions as a transducing boundary for visual perception making it an essential factor for sight. The RPE also functions as a metabolically complex and functional cell layer that is responsible for the local homeostasis and maintenance of the extra photoreceptor environment. Thus one of the suggested method of treating such diseases would be regenerating these RPE cells. As such, we intend to grow these cells using a synthetic scaffold to provide a stable environment that reduces the batch effects found in natural scaffolds. Stiffness of the scaffold will also be investigated to determine the optimal Young’s modulus for cultivating these cells. The cells will be generated into a monolayer cell sheet and their functions such as formation of tight junctions and gene expression patterns will be assessed to evaluate the cell sheet quality compared to a native RPE tissue.

Keywords: RPE, scaffold, characterization, biomaterials, colloids and nanomedicine

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Authors: Dong-An Wang

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All kinds of microspheres have been extensively employed as carriers for drug, gene and therapeutic cell delivery. Most therapeutic cell delivery microspheres rely on a two-step methodology: fabrication of microspheres and subsequent seeding of cells onto them. In this study, we have developed a novel one-step cell encapsulation technique using a convenient and instant water-in-oil single emulsion approach to form cell-encapsulated gelatin microspheres. This technology is adopted for hyaline cartilage tissue engineering, in which autologous chondrocytes are used as therapeutic cells. Cell viability was maintained throughout and after the microsphere formation (75-100 µm diameters) process that avoids involvement of any covalent bonding reactions or exposure to any further chemicals. Further encapsulation of cell-laden microspheres in alginate gels were performed under 4°C via a prompt process. Upon the formation of alginate constructs, they were immediately relocated into CO2 incubator where the temperature was maintained at 37°C; under this temperature, the cell-laden gelatin microspheres dissolved within hours to yield similarly sized cavities and the chondrocytes were therefore suspended within the cavities inside the alginate gel bulk. Hence, the gelatin cell-laden microspheres served two roles: as cell delivery vehicles which can be removable through temperature curing, and as porogens within an alginate hydrogel construct to provide living space for cell growth and tissue development as well as better permeability for mutual diffusions. These cell-laden microspheres, namely “temperature-cured dissolvable gelatin microsphere based cell carriers” (tDGMCs), were further encapsulated in a chondrocyte-laden alginate scaffold system and analyzed by WST-1, gene expression analyses, biochemical assays, histology and immunochemistry stains. The positive results consistently demonstrated the promise of tDGMC technology in delivering these non-anchorage dependent cells (chondrocytes). It can be further conveniently translated into delivery of other non-anchorage dependent cell species, including stem cells, progenitors or iPS cells, for regeneration of tissues in internal organs, such as engineered hepatogenesis or pancreatic regeneration.

Keywords: biomaterials, tissue engineering, microsphere, hydrogel, porogen, anchorage dependence

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Authors: Bui Phuong Linh, Yuki Sakakibara, Ryuto Tanaka, Elizabeth H. Pigney, Taishi Hashiguchi

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Non-alcoholic steatohepatitis (NASH) is a chronic liver disease, often associated with type II diabetes, which sometimes progresses to more serious conditions such as liver fibrosis and hepatocellular carcinoma (HCC). NASH has become an important health problem worldwide, buttherapeutic agents for NASH have not yet been approved, and animal models with high clinical correlation are required. TheSTAM™ mouse shows the same pathological progression as human NASH patients and has been widely used for both drug efficacy and basic research, such as lipid profiling and gut microbiota research. In this study, we analyzed the RNA-seq data of STAM™mice at each pathological stage (steatosis, steatohepatitis, liver fibrosis, and HCC) and examined the clinical correlation at the genetic level. NASH was induced in male mice by a single subcutaneous injection of 200 µg streptozotocin solution 2 days after birth and feeding with high fat dietafter 4 weeks of age. The mice were sacrificed and livers collected at 6, 8, 10, 12, 16, and 20 weeks of age. For liver samples, the left lateral lobe was snap frozen in liquid nitrogen and stored at -80˚C for RNA-seq analysis. Total RNA of the cells was isolated using RNeasy mini kit. The gene expression of the canonical pathways in NASH progression from steatosis to hepatocellular carcinoma were analyzed, such as immune system process, oxidation-reduction process, lipid metabolic process. Moreover, since it has been reported that genetic traits are involved in the development of NASH-HCC, we next analyzed the genetic mutations in the STAM™mice. The number of individuals showing mutations in Mtorinvolved in Insulin signaling increases as the disease progresses, especially in the liver cancer phase. These results indicated a clinical correlation of gene profiles in the STAM™mouse.

Keywords: steatosis, non-alcoholic steatohepatitis, fibrosis, hepatocellular carcinoma, RNA-seq

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Authors: Mei Chen, Yingping Hou, Michelle Hao, Soheil Aghamohammadzadeh, Esteban Terzo, Roger Clark, Vijay Modur

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Background: Recessive Dystrophic Epidermolysis Bullosa (RDEB) is a genetic skin condition characterized by skin tearing and unremitting blistering upon minimal trauma. Repeated blistering, fibrosis, and scarring lead to aggressive squamous cell carcinoma later in life. RDEB is caused by mutations in the COL7A1 gene encoding collagen type VII (C7), the major component of anchoring fibrils mediating epidermis-dermis adherence. Nonsense mutations in the COL7A1 gene of a subset of RDEB patients leads to premature termination codons (PTC). Similarly, most Junctional Epidermolysis Bullosa (JEB) cases are caused by nonsense mutations in the LAMB3 gene encoding the β3 subunit of laminin 332. Currently, there is an unmet need for the treatment of RDEB and JEB. Zikani Therapeutics has discovered an array of macrocyclic compounds with ring structures similar to macrolide antibiotics that can facilitate readthrough activity of nonsense mutations in the COL7A1 and LAMB3 genes by acting as Ribosome Modulating Agents (RMAs). The medicinal chemistry synthetic advancements of these macrocyclic compounds have allowed targeting the human ribosome while preserving the structural elements responsible for the safety and pharmacokinetic profile of clinically used macrolide antibiotics. Methods: C7 expression was used as a measure of readthrough activity by immunoblot assays in two primary human fibroblasts from RDEB patients (R578X/R578X and R163X/R1683X-COL7A1). Similarly, immunoblot assays in C325X/c.629-12T > A-LAMB3 keratinocytes were used to measure readthrough activity for JEB. The relative readthrough activity of each compound was measured relative to Gentamicin. An imaging-based fibroblast migration assay was used as an assessment of C7 functionality in RDEB-fibroblasts over 16-20 hrs. The incubation period for the above experiments was 48 hrs for RDEB fibroblasts and 72 hours for JEB keratinocytes. Results: 9 RMAs demonstrated increased protein expression in both patient RDEB fibroblasts. The highest readthrough activity at tested concentrations without cytotoxicities increased protein expression up to 179% of Gentamicin (400 µg/ml), with favored readthrough activity in R163X/R1683X-COL7A1 fibroblasts. Concurrent with protein expression, fibroblast hypermotility phenotype observed in RDEB was rescued by reducing motility by ~35% to WT levels (the same level as 690 µM Gentamicin treated cells). Laminin β3 expression was also shown to be increased by 6 RMAs in keratinocytes to 33-83% of (400 µg/ml) Gentamicin. Conclusions: To date, 9 RMAs have been identified that enhance the expression of functional C7 in a mutation-dependent manner in two different RDEB patient fibroblast backgrounds (R578X/R578X and R163X/R1683X-COL7A1). A further 6 RMAs have been identified that enhance the readthrough of C325X-LAMB3 in JEB patient keratinocytes. Based on the clinical trial conducted by us with topical gentamycin in 2017, Zikani’s RMAs achieve clinically significant levels of read-through for the treatment of recessive dystrophic and Junctional Epidermolysis Bullosa.

Keywords: epidermolysis bullosa, nonsense mutation, readthrough, ribosome modulation

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Authors: Shafieeh Mansoori, Fatemeh Yazdian, Ashrafsadat Hatamian, Majid Azizi

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Monascus purpureus, which has a special metabolite with many therapeutic and medicinal properties including antioxidant, antibiotic, anti-hypercholesterolemia, and immunosuppressive properties, is a traditional Chinese fermentation fungus and is used as a natural dietary supplement. Production of desired metabolites actually determined by optimized growth which is supported by some factors such as substrates and Monascus strains type, moisture content of the fermentation mixture, aeration, and control of contamination issues. In this experiment, M. purpureus PTCC5305 was cultured in both the liquid and solid culture medium. The former medium contain YMP (yeast extract, maltose and peptone), PGC (peptone, glucose complex), and GYP (glucose, yeast extract and peptone) medium. After 8 days, the best medium for the cell production was PGC agar medium on solid culture with 0.28 g dry weight of cell mass whereas the best liquid culture was GYP medium with 3.5 g/l dry weight of cell mass. The lowest cell production was on YMP agar with 0.1 g dry weight of cell mass and then YMP medium with 2.5 g/l dry cell weight.

Keywords: Monascus purpureus, solid state fermentation, submerged culture, Chinese fermentation fungus

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Authors: Armin Khaghani Boroujeni, Leila Dehghani, Parham Talebi Boroujeni, Sahar Rostamian, Ali Asilian

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Background: Hair loss is a common complaint observed in both genders. Androgenetic alopecia is known pattern for hair loss. To assess new regenerative strategies (PRP, A-SC-BT, conditioned media, exosome-based treatments) compared to conventional therapies for hair loss or hair regeneration, an updated review was undertaken. To address this issue, we carried out this systematic review to comprehensively evaluate the efficacy of cell-based therapies on hair loss. Methods: The available online databases, including ISI Web of Science, Scopus, and PubMed, were searched systematically up to February 2022. The quality assessment of included studies was done using the Cochrane Collaboration's tool. Results: As a result, a total of 90 studies involving 2345 participants were included in the present study. The enrolled studies were conducted between 2010 and 2022. The subjects’ mean age ranged from 19 to 55.11 years old. Approaches using platelet rich plasma (PRP) provide a beneficial impact on hair regrowth. However, other cell-based therapies, including stem cell transplant, stem cell-derived conditioned medium, and stem cell-derived exosomes, revealed conflicting evidence. Conclusion: However, cell-based therapies for hair loss are still in their infancy, and more robust clinical studies are needed to better evaluate their mechanisms of action, efficacy, safety, benefits, and limitations. In this review, we provide the resources to the latest clinical studies and a more detailed description of the latest clinical studies concerning cell-based therapies in hair loss.

Keywords: cell-based therapy, exosome, hair restoration, systematic review

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Authors: Qi Liu, Jiqin Yao, Xiaohu Zhou, Bo Zheng

Abstract:

The first artificial cell was produced by Thomas Chang in the 1950s when he was trying to make a mimic of red blood cells. Since then, many different types of artificial cells have been constructed from one of the two approaches: a so-called bottom-up approach, which aims to create a cell from scratch, and a top-down approach, in which genes are sequentially knocked out from organisms until only the minimal genome required for sustaining life remains. In this project, bottom-up approach was used to build a new cell-free expression system which mimics artificial cell that capable of protein expression and communicate with each other. The artificial cells constructed from the bottom-up approach are usually lipid vesicles, polymersomes, hydrogels or aqueous droplets containing the nucleic acids and transcription-translation machinery. However, lipid vesicles based artificial cells capable of communication present several issues in the cell communication research: (1) The lipid vesicles normally lose the important functions such as protein expression within a few hours. (2) The lipid membrane allows the permeation of only small molecules and limits the types of molecules that can be sensed and released to the surrounding environment for chemical communication; (3) The lipid vesicles are prone to rupture due to the imbalance of the osmotic pressure. To address these issues, the hydrogel-based artificial cells were constructed in this work. To construct the artificial cell, polyacrylamide hydrogel was functionalized with Acrylate PEG Succinimidyl Carboxymethyl Ester (ACLT-PEG2000-SCM) moiety on the polymer backbone. The proteinaceous factors can then be immobilized on the polymer backbone by the reaction between primary amines of proteins and N-hydroxysuccinimide esters (NHS esters) of ACLT-PEG2000-SCM, the plasmid template and ribosome were encapsulated inside the hydrogel particles. Because the artificial cell could continuously express protein with the supply of nutrients and energy, the artificial cell-artificial cell communication and artificial cell-natural cell communication could be achieved by combining the artificial cell vector with designed plasmids. The plasmids were designed referring to the quorum sensing (QS) system of bacteria, which largely relied on cognate acyl-homoserine lactone (AHL) / transcription pairs. In one communication pair, “sender” is the artificial cell or natural cell that can produce AHL signal molecule by synthesizing the corresponding signal synthase that catalyzed the conversion of S-adenosyl-L-methionine (SAM) into AHL, while the “receiver” is the artificial cell or natural cell that can sense the quorum sensing signaling molecule form “sender” and in turn express the gene of interest. In the experiment, GFP was first immobilized inside the hydrogel particle to prove that the functionalized hydrogel particles could be used for protein binding. After that, the successful communication between artificial cell-artificial cell and artificial cell-natural cell was demonstrated, the successful signal between artificial cell-artificial cell or artificial cell-natural cell could be observed by recording the fluorescence signal increase. The hydrogel-based artificial cell designed in this work can help to study the complex communication system in bacteria, it can also be further developed for therapeutic applications.

Keywords: artificial cell, cell-free system, gene circuit, synthetic biology

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Authors: Rubab Z. Kahlon, Ibtisam Butt, Isma Younis, Aamer G. Mufti

Abstract:

Worldwide lung cancer 1.61 million cases were seen in both genders. Lung carcinoma is the major cause of both morbidity and mortality in the world. Purpose of the present study was to describe the spatio- temporal trends of lung cancer in both genders. A retrospective study was conducted. Total 1498 patients of lung carcinoma were examined. Only lung cancer patients from all over the Punjab were included in the present study. MS Excel 2010 was used for data tabulation and calculation while the Arc GIS version 9.3 was used for geographical representation of the data. 1498 cases of Lung cancer were found from 2008-2012. The number of male patients was 1236 and female was 262. Majority of the patients were from Lahore districts with 807 patients. Lung cancer was more prevalent in male as compared to female in our region. Increase in the prevalence of lung cancer was prominently seen in the most populated and industrial areas of the Punjab province. Time trend of five years showed fluctuation in the lung cancer incidence during the study period.

Keywords: districts, gender, lung cancer trends, Punjab province of Pakistan

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Authors: Mojdeh Mohseni

Abstract:

In the context of tissue engineering, the effect of microtopography as afforded by scaffold morphology is an important design parameter. Since the morphology of pores can effect on cell behavior, in this study, porous Chitosan (CHIT) - Gelatin (GEL)- Alginate (ALG) scaffolds with microtubule orientation structure were manufactured by unidirectional freeze-drying method and the effect of pore morphology on differentiation of Mesenchymal Stem Cells (MSCs) was investigated. This study showed that, the provided scaffold with natural polymer had good properties for cell behavior and the pores with highest orientation rate have produced appropriate substrate for the differentiation of stem cells.

Keywords: Chitosan, gelatin, Alginate, pore morphology, stem cell differentiation

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Authors: Zahra Shokrolahi, Mohammad Reza Atashzar

Abstract:

The goals of treating patients with breast cancer are to cure the disease, prolong survival, and improve quality of life. Immune cells in the tumor microenvironment have an important role in regulating tumor progression. The term of cellular immunotherapy refers to the administration of living cells to a patient; this type of immunotherapy can be active, such as a dendritic cell (DC) vaccine, in that the cells can stimulate an anti-tumour response in the patient, or the therapy can be passive, whereby the cells have intrinsic anti-tumour activity; this is known as adoptive cell transfer (ACT) and includes the use of autologous or allogeneic lymphocytes that may, or may not, be modified. The most important breast cancer cellular immunotherapies involving the use of T cells and natural killer (NK) cells in adoptive cell transfer, as well as dendritic cells vaccines. T cell-based therapies including tumour-infiltrating lymphocytes (TILs), engineered TCR-T cells, chimeric antigen receptor (CAR T cell), Gamma-delta (γδ) T cells, natural killer T (NKT) cells. NK cell-based therapies including lymphokine-activated killers (LAK), cytokine-induced killer (CIK) cells, CAR-NK cells. Adoptive cell therapy has some advantages and disadvantages some. TILs cell strictly directed against tumor-specific antigens but are inactive against tumor changes due to immunoediting. CIK cell have MHC-independent cytotoxic effect and also need concurrent high dose IL-2 administration. CAR T cell are MHC-independent; overcome tumor MHC molecule downregulation; potent in recognizing any cell surface antigen (protein, carbohydrate or glycolipid); applicable to a broad range of patients and T cell populations; production of large numbers of tumor-specific cells in a moderately short period of time. Meanwhile CAR T cells capable of targeting only cell surface antigens; lethal toxicity due to cytokine storm reported. Here we present the most popular cancer cellular immunotherapy approaches and discuss their clinical relevance referring to data acquired from clinical trials .To date, clinical experience and efficacy suggest that combining more than one immunotherapy interventions, in conjunction with other treatment options like chemotherapy, radiotherapy and targeted or epigenetic therapy, should guide the way to cancer cure.

Keywords: breast cancer , cell therapy , CAR T cell , CIK cells

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Authors: Suhadiyana Hanapi, Alhassan Salami Tijani, W. A. N Wan Mohamed

Abstract:

In this paper, a prototype PEM fuel cell vehicle integrated with a 1 kW air-blowing proton exchange membrane fuel cell (PEMFC) stack as a main power sources has been developed for a lightweight cruising vehicle. The test vehicle is equipped with a PEM fuel cell system that provides electric power to a brushed DC motor. This vehicle was designed to compete with industrial lightweight vehicle with the target of consuming least amount of energy and high performance. Individual variations in driving style have a significant impact on vehicle energy efficiency and it is well established from the literature. The primary aim of this study was to assesses the power and fuel consumption of a hydrogen fuel cell vehicle operating at three difference driving technique (i.e. 25 km/h constant speed, 22-28 km/h speed range, 20-30 km/h speed range). The goal is to develop the best driving strategy to maximize performance and minimize fuel consumption for the vehicle system. The relationship between power demand and hydrogen consumption has also been discussed. All the techniques can be evaluated and compared on broadly similar terms. Automatic intelligent controller for driving prototype fuel cell vehicle on different obstacle while maintaining all systems at maximum efficiency was used. The result showed that 25 km/h constant speed was identified for optimal driving with less fuel consumption.

Keywords: prototype fuel cell electric vehicles, energy efficient, control/driving technique, fuel economy

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Authors: Isobel Hambleton, Mark Carrington

Abstract:

Trypanosoma brucei, the causal agent of a range of diseases in humans and livestock, evades the mammalian immune system through a population survival strategy based on the expression of a series of antigenically distinct variant surface glycoproteins (VSGs). RNAi mediated knockdown of the active VSG gene triggers a precytokinesis cell cycle arrest. To determine whether this phenotype is the result of reduced VSG transcript or depleted VSG protein, we used morpholino antisense oligonucleotides to block translation of VSG mRNA. The same precytokinesis cell cycle arrest was observed, suggesting that VSG protein abundance is monitored closely throughout the cell cycle. An inducible expression system has been developed to test various GPI-anchored proteins for their ability to rescue this cell cycle arrest. This system has been used to demonstrate that wild-type VSG expressed from a T7 promoter rescues this phenotype. This indicates that VSG expression from one of the specialised bloodstream expression sites (BES) is not essential for cell division. The same approach has been used to define the minimum essential features of a VSG necessary for function.

Keywords: bloodstream expression site, morpholino, precytokinesis cell cycle arrest, variant surface glycoprotein

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Authors: Sanjay Tushar Choudhary

Abstract:

This paper focuses on the thermodynamic analysis of Solid Oxide Fuel Cell (SOFC). In the present work the SOFC has been modeled to work with internal reforming of fuel which takes place at high temperature and direct energy conversion from chemical energy to electrical energy takes place. The fuel-cell effluent is a high-temperature steam which can be used for co-generation purposes. Syn-gas has been used here as fuel which is essentially produced by steam reforming of methane in the internal reformer of the SOFC. A thermodynamic model of SOFC has been developed for planar cell configuration to evaluate various losses in the energy conversion process within the fuel cell. Cycle parameters like fuel utilization ratio and the air-recirculation ratio have been varied to evaluate the thermodynamic performance of the fuel cell. Output performance parameters like terminal voltage, cell-efficiency and power output have been evaluated for various values of current densities. It has been observed that a combination of a lower value of air-circulation ratio and higher values of fuel utilization efficiency gives a better overall thermodynamic performance.

Keywords: current density, SOFC, suel utilization factor, recirculation ratio

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Authors: Muskan Parmar, Musthafa Ottakam Thotiyl

Abstract:

The rising need for portable energy sources has led to advancements in direct liquid fuel cells (DLFCs) using various fuels like alcohol, ammonia, hydrazine, and vitamin C. Traditional precious metal catalysts improve reaction speeds but are expensive and prone to poisoning. Our study reveals how non-precious metal organometallic complexes, combined with smartly designed ligands, can significantly boost performance. The key is a unique interaction between the substrate (fuel) and the ligand, which creates a "dragging" effect that enhances reaction rates. By using this approach with a ferricyanide/ferrocyanide half-cell reaction, we developed a vitamin C fuel cell without precious metals. This fuel cell achieves an open circuit voltage of ∼950 mV, a peak power density of ∼97 mW cm⁻², and a peak current density of ∼215 mA cm⁻². Impressively, its performance is about 1.7 times better than traditional precious metal-based DLFCs. This highlights the potential of substrate ligand chemistry in the creation of sustainable DLFCs for efficient energy conversion.

Keywords: molecular electrocatalysts, vitamin C fuel cell, proton charge assembly, ferricyanide half-cell chemistry

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Authors: Hamed Karimian, Noraziah Nordin, Mohamad Ibrahim Noordin, Syam Mohan, Mahboubeh Razavi, Najihah Mohd Hashim, Happipah Mohd Ali

Abstract:

Satureja bachtiarica Bunge is a perennial medicinal plant belonging to the Lamiaceae family and endemic species in Iran. Satureja bachtiarica Bunge with the local name of Marzeh koohi is edible vegetable use as flavoring agent, anti-bacterial and to relieve cough and indigestion. In this study, the anti-cancer effect of Satureja bachtiarica Bunge on the MDA-MB-231 cell line as an Breast cancer cell model has been analyzed for the first time. Satureja bachtiarica Bunge was extracted using different solvents in the order of increasing polarity. Cytotoxicity activity of hexane extract of Satureja bachtiarica Bunge (SBHE) was observed using MTT assay. Acridine orange/Propidium iodide staining was used to detect early apoptosis; Annexin-V-FITC assay was carried out to observe the detection of cell-surface Phosphatidylserine (PS), with Annexin-Vserving as a marker for apoptotic cells. Caspase 3/7, 8 and-9 assays showed significantly activation of caspase-9 where lead intrinsic mitochondrial pathway. Bcl-2/Bax expressions and cell cycle arrest were also investigated. SBHE had exhibited significantly higher cytotoxicity against MDA-MB-231 Cell line compare to other cell lines. A significant increase in chromatin condensation in the cell nucleus was observed by fluorescence analysis. Treatment of MDA-MB-231 cells with SBHE encouraged apoptosis, by down-regulating Bcl-2 and up-regulating Bax, which lead the activation of caspase 9. Moreover, SBHE treatment significantly arrested MDA-MB-231 cells in the G1 phase. Together, the results presented in this study demonstrated that SBHE inhibited the proliferation of MDA-MB-231 cells, leading cell cycle arrest and programmed cell death, which was confirmed to be through the mitochondrial pathway.

Keywords: Satureja bachtiarica Bunge, MDA-MB-231, apoptosis, annexin-V, cell cycle

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