Evaluating Drug Resistant Mutations to HCV NS3 Protease Inhibitors in Iranian Naïve Patients

International Journal of Peptide Research and Therapeutics - Hepatitis C virus (HCV) is an important causative agent of acute and chronic hepatitis. The non-structural protein 3 (NS3) of HCV...     

Quality control in cervicovaginal cytology by cytohistological correlation

N. Izadi‐Mood, S. Sarmadi and S. Sanii
Quality control in cervicovaginal cytology by cytohistological correlation Objective: Frequent studies attest to the correlation of cytological interpretations with defined histopathological entities. Nevertheless, as part of quality control, cytology laboratories are required to compare Papanicolaou smear reports with those of cervical biopsies to search for discrepancies. We have attempted to determine and categorize the causes of existing discrepancies in our laboratory in order to clarify the source of errors. Methods: We reviewed 670 cervical smears that were paired with subsequent punch biopsy or endocervical curettage samples, obtained within 2 months of the cytology, and found out that 60 smear‐biopsy pairs were discrepant regarding the diagnosis. These cases were categorized into four error groups after careful re‐evaluation of the original smear and biopsy slides. Results: In 51 (85%) of 60 cervical smear‐biopsy pairs with reports that disagreed, the initial diagnoses of both cervical smear and biopsy were confirmed by the review opinion; in these cases, cytology and biopsy ‘sampling errors’ were responsible for 40 and 11 instances of discrepancy, respectively. Seven cases (11.1%) were discrepant due to ‘smear interpretation errors’ and consisted of five cases with initial under‐diagnosis and two cases with initial over‐diagnosis. One case (1.7%) was due to ‘screener error’. In another case, discordance was due to cervical ‘biopsy interpretation error’, with initial over‐diagnosis as squamous intraepithelial lesion. Conclusion: In this retrospective study, we determined the causes of cytohistological discrepancies in cervical samples. The main explanation for discrepancy was ‘sampling error’.     

Combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by chlorpyrifos

The aim of this study was to investigate the combination effect of exercise training and eugenol supplementation on the hippocampus apoptosis induced by CPF. 64 adult male albino rats were randomly selected and devided into eight groups of eight including: control, exercise (EXE), chlorpyrifos (CPF), Control?+?Oil (Co?+?Oil), Control?+?DMSO (Co?+?DMSO), chlorpyrifos?+?eugenol (CPF?+?Sup), chlorpyrifos?+?exercise (CPF?+?Exe) and, chlorpyrifos?+?exercise?+?eugenol (CPF?+?Exe?+?Eu). Four experimental groups received intraperitoneal injection (5 days a week) of 3.0 mg/kg body weight CPF in DMSO for 6 consecutive weeks. The exercise groups performed aerobic 5 days per week over 4 weeks. Eugenol were administered by gavage. Finally, the animals were sacrificed using CO₂ gas (a half of the rats were anesthetized with ketamine and xylazine and then perfused) to evaluate hippocampus histology and parameters. The results of this study showed that CPF injection significantly decreased BDNF, AChE and ATP in CA1 area of the hippocampus (p ? 0.05). Also, CA1 apoptosis by tunnel assay, it was found that CPF receiving groups with different dosage, showed a significant increase compared to other groups, which was confirmed by increasing cytochrome C and procaspase-3 in CPF groups (p ? 0.05). The result of this study show that 4 weeks of exercise training and eugenol supplementation does not improve the destructive effects of CPF in CA1 area of the hippocampus. As a result, it is recommended that future studies longer periods for treatment with exercise and eugenol supplementation.

     

Paraoxonase Arg 192 allele is an independent risk factor for three-vessel stenosis of coronary artery disease

The role of the paraoxonase (PON1) codon 192 polymorphism [glutamine (Q)/arginine (R)] in coronary artery disease (CAD) is controversial. The aim of the present study was to evaluate whether the PON1 gene polymorphism is an independent risk factor for severity of coronary artery disease in patients from west of Iran. The PON1-Arg-192 genotypes were detected by PCR-RFLP in 414 individuals undergoing their first coronary angiography. Patients were placed into one of two groups: CAD and control without CAD or diabetes. The frequency of PON1-Arg-192 allele was significantly higher in the CAD (23.4 vs. 16%, P = 0.032) than in the control group and there was a higher risk of developing CAD (OR = 1.6, P = 0.02). In addition, this difference remained significant after adjustment for without history of diabetes (OR = 1.47, P = 0.048), presence of normolipidemia and absence of history of blood pressure (OR = 1.4, P = 0.05). This result indicated PON1-Arg-192 allele is a risk factor of CAD also when correcting for conventional risk factors. We found a significant association between the PON1-Arg-192 genotype (QR + RR) and the extent of CAD in CAD patients and CAD subjects without diabetes, represented by the increased frequency of three-vessel disease with OR = 1.49, P = 0.046; χ2 = 3.82, P = 0.048 and OR = 1.46, P = 0.05; χ2 = 3.48, P = 0.051, respectively. The CAD patients carrying PON1-Arg-192 genotype (QR + RR) had lower plasma HDL-C level (P = 0.019) and higher plasma LDL-C(P = 0.01) and TG(P = 0.05). Our results indicated that PON1-Arg-192 allele can be important independent risk factor of CAD in a west population of Iran, with carriers of PON1-Arg-192 having an increased frequency of three-vessel disease and also having a distinct plasma lipids profile. Larger collaborative studies are needed to confirm these results.     

RAS/MAPK signaling functions in oxidative stress,DNA damage response and cancer progression

Mitogen-activated protein kinase (MAPK) signaling pathways organize a great constitution network that regulates several physiological processes, like cell growth, differentiation, and apoptotic cell death. Due to the crucial importance of this signaling pathway, dysregulation of the MAPK signaling cascades is involved in the pathogenesis of various human cancer types. Oxidative stress and DNA damage are two important factors which in common lead to carcinogenesis through dysregulation of this signaling pathway. Reactive oxygen species (ROS) are a common subproduct of oxidative energy metabolism and are considered to be a significant physiological modulator of several intracellular signaling pathways including the MAPK pathway. Studies demonstrated that the MAP kinases extracellular signal-regulated kinase (ERK) 1/2 and p38 were activated in response to oxidative stress. In addition, DNA damage is a partly common circumstance in cell life and may result in mutation, cancer, and even cell death. Recently, accumulating evidence illustrated that the MEK/ERK pathway is associated with the suitable performance of cellular DNA damage response (DDR), the main pathway of tumor suppression. During DDR, the MEK/ERK pathway is regularly activated, which contributes to the appropriate activation of DDR checkpoints to inhibit cell division. Therefore, the aim of this review is to comprehensively discuss the critical function of MAPK signaling in oxidative stress, DNA damage, and cancer progression.     

Favorable Mixing Thermodynamics in Ternary Polymer Blends for Realizing High Efficiency Plastic Solar Cells

Ternary blends with broad spectral absorption have the potential to increase charge generation in organic solar cells but feature additional complexity due to limited intermixing and electronic mismatch. Here, a model system comprising the polymers poly[5,5‐bis(2‐butyloctyl)‐(2,2‐bithiophene)‐4,4‐dicarboxylate‐alt‐5,5‐2,2‐bithiophene] (PDCBT) and PTB7‐Th and PC₇₀BM as an electron accepting unit is presented. The power conversion efficiency (PCE) of the ternary system clearly surpasses the performance of either of the binary systems. The photophysics is governed by a fast energy transfer process from PDCBT to PTB7‐Th, followed by electron transfer at the PTB7‐Th:fullerene interface. The morphological motif in the ternary blend is characterized by polymer fibers. Based on a combination of photophysical analysis, GIWAXS measurements and calculation of the intermolecular parameter, the latter indicating a very favorable molecular affinity between PDCBT and PTB7‐Th, it is proposed that an efficient charge generation mechanism is possible because PTB7‐Th predominantly orients around PDCBT filaments, allowing energy to be effectively relayed from PDCBT to PTB7‐Th. Fullerene can be replaced by a nonfullerene acceptor without sacrifices in charge generation, achieving a PCE above 11%. These results support the idea that thermodynamic mixing and energetics of the polymer–polymer interface are critical design parameter for realizing highly efficient ternary solar cells with variable electron acceptors.     

Protein profiles of Spodoptera litura (F.) male accessory reproductive gland and its secretions

Protein profiles of the male accessory reproductive glands of a polyphagous pest, Spodoptera litura (Lepidoptera: Noctuidae) and their glandular secretions were analyzed by electrophoresis under denaturing conditions. The study revealed the presence of 23 proteins in the glands and 14 in the secretions. The molecular weights of the gland proteins ranged from 163 to 3.8 KD whereas that of secretions ranged from 100 to 3.8 KD. The 9 low molecular weight proteins of the secretions are a characteristic feature. It is suggested that the secretions may contain a sex peptide that has a role in the fertility and fecundity of the females.     

Kynurenic Acid and Gpr35 Regulate Adipose Tissue Energy Homeostasis and Inflammation

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Sublethal concentration of H<Subscript>2</Subscript>O<Subscript>2</Subscript> enhances the protective effect of mesenchymal stem cells in rat model of spinal cord injury

Objective

To investigate the effect of H₂O₂ on the migration and antioxidant defense of mesenchymal stem cells (MSCs) and the neurotrophic effects of H₂O₂-treated MSCs on spinal cord injury (SCI).

Results

Sublethal concentrations of H₂O₂ decreased cell migration and expression of CXCR4 and CCR2 as well as Nrf2 expression in MSCs. In the second phase, transplantation of treated and untreated MSCs to SCI caused minor changes in locomotor dysfunction. There was a significantly difference between cell-treated and spinal cord injury groups in expression of BDNF (brain-derived neurotrophic factor). Transplantation of H₂O₂-treated cells caused an increase in BDNF expression compared to non-treated cells.

Conclusion

Transplantation of H₂O₂-treated stem cells may have protective effects against SCI through by increasing neurotrophic factors.

     

Roles for Kisspeptin in proliferation and differentiation of spermatogonial cells isolated from mice offspring when the cells are cocultured with somatic cells

Kisspeptin (Kp) expression in testis has caused most of the recent research surveying its functional role in this organ. This peptide influences spermatogenesis and sperm capacitation, so it is considered as a regulator of reproduction. Kp roles exert through hypothalamic/pituitary/gonadal axis. We aimed to evaluate direct roles for Kp on proliferation and differentiation of spermatogonial cells (SCs) when the cells are cocultured with somatic cells. Somatic cells and SCs were isolated from adult azoospermic and newborn mice and then enriched using a differential attachment technique. After the evaluation of identity and colonization for SCs, the cells were cocultured with somatic cells, and three doses of Kp (10⁻⁸-10⁻⁶ M) was assessed on proliferation (through evaluation of MVH and ID4 markers) and differentiation (via evaluation of c-Kit and SCP₃, TP_1, TP₂, and, Prm₁ markers) of the coculture system. Investigations were continued for four succeeding weeks. At the end of each level of testosterone in the culture media was also evaluated. We found positive influence from Kp on proliferative and differentiative markers in SCs cocultured with somatic cells. These effects were dose-dependent. There was no effect for Kp on testosterone level. From our findings, we simply conclude that Kp as a neuropeptide for influencing central part of reproductive axis could also positively affect peripheral processes related to spermatogenesis without having an effect on steroidogenesis.