Ameliorative Effects of Vitamin C and Methanolic Extract of Broccoli on Cyclophosphamide-induced Poisoning in Ovary of Rat

Abstract Introduction: Considering the importance of using herbal compounds to reduce the side effects of cyclophosphamide (CPH), the current study aimed to evaluate the effects of broccoli extract and Vitamin C on ovarian poisoning with CPH. Materials and methods: Four equal groups of 48 adult female Wistar rats were formed. The first group that was control received physiological saline orally without treatment. A 200 mg/kg dose of CPH was administered intraperitoneally to the second group. For the third group, CPH was supplemented with 300 mg/kg of Vitamin C, and methanol extract of broccoli 300 mg/kg was used in the fourth group. The serum total antioxidant capacity (TAC), interleukin-1 and tumor necrosis factor alpha (TNFα) and ovarian tissue glutathione peroxidase (GPx), superoxide dismutase (SOD), malondialdehyde (MDA), catalase (CAT), were measured. At the end of the study, the ovarian tissue was cut and stained for histopathological investigations. Results: Ovarian tissue GPx, CAT, and SOD values indicated a significant decrease in the CPH group compared to other groups. In the CPH plus broccoli group, there was a significant decrease in MDA ovarian tissue and IL-1 and TNF-α in serum, compared to the CPH group. There were significant negative changes in ovarian cells of the CPH group, compared to the control and other treatment groups. Conclusion: The current study suggested that administrating broccoli extract plus CPH could increase the superior antioxidant potential, compared to Vitamin C. This can potentially decrease CPH-induced damage to the ovary of rats, thereby improving their fertility status. https://jlar.rovedar.com/index.php/JLAR/article/view/2

Caenorhabditis elegans as a Valuable Model for Studying Apoptosis and Autophagy in Cancer Development: Current insights, Future directions, and Challenges

Abstract Despite significant progress in the fight against cancer, cancer treatment remains a significant public health concern and a societal burden worldwide. To develop better intervention strategies to counter tumor development, it is important to understand the molecular and cellular mechanisms underlying oncogenic diseases. In-vivo and in-vitro models have traditionally been utilized to understand the biological processes involved in cancer, including apoptosis, proliferation, angiogenesis, invasion, metastasis, genome instability, and metabolism. The present review aims to look at the way Caenorhabditis elegans (C. elegans) can affect cancer cellular and molecular bases, concentrating on mechanisms like apoptosis and autophagy. In recent years, . elegans has emerged as a promising model organism for studying the molecular basis of tumorigenesis. This model organism is attractive since it is genetically tractable and has a simple and well-understood anatomy. The C. elegans exhibits conserved cellular pathways and mechanisms relevant to human diseases, including cancer. Furthermore, C. elegans has been used to study the roles of tumor suppressor genes and oncogenes in tumorigenesis. In conclusion, C. elegans is an emerging animal model that has the potential to facilitate the development of better intervention strategies to prevent or counter tumor development and to advance our understanding of cancer progression with further research. https://jlar.rovedar.com/index.php/JLAR/article/view/1

CRISPR/Cas9-mediated Genome Editing: In vivo Review

Abstract The CRISPR/Cas9 system has been a game-changer in genetics and biotechnology. This study aimed to investigate the existing in vivo uses and their potential to increase our understanding of gene function and biological processes in animal models. With its remarkable precision and accuracy, researchers can now easily edit specific genes within cells and organisms. This technology has opened up new avenues for studying genetic diseases and developing therapies to treat them. One of the most significant advantages of the CRISPR/Cas9 system is its ability to create precise cellular and animal models of human diseases. This allows researchers to investigate the role of genetics in disease development and to develop more effective therapies. For example, the system can correct genetic mutations that cause cystic fibrosis or sickle cell anemia. The therapeutic potential of CRISPR/Cas9 is enormous, especially in gene therapy. By correcting specific genetic mutations, the system can potentially treat human diseases that are currently untreatable with conventional therapies. However, some challenges still need to be addressed before this technology can be used in clinical settings. Despite these challenges, the potential of CRISPR/Cas9 to revolutionize the field of genetics and biotechnology cannot be overstated. Ultimately, this technology has the potential to transform medicine by providing new therapies for a wide range of genetic diseases. https://jlar.rovedar.com/index.php/JLAR/article/view/1

A Case of Necrotizing Keratoscleritis in Primary Sjogren's Syndrome

We report on a case of necrotizing keratoscleritis in primary Sjogren's syndrome. A 66-year-old female patient who was complaining of ocular pain, tearing and decreased vision in her right eye for the previous two days was admitted to our hospital. Visual acuity in the right eye was hand movement, and initial examination showed a 3.0 × 1.8 mm uveal mass bulging through a corneoscleral melting site in the nasal region of the right eye. Positive anti-nuclear antibody was identified at a titer of 1:320 with a speckled pattern, and both Sjogren's syndrome A and Sjogren's syndrome B antibody tests were positive, with titers >200 U/mL. A technetium 99m pertechnetate salivary scan revealed chronic sialoadenitis in the submandibular glands. We diagnosed the lesion as necrotizing keratoscleritis due to primary Sjogren's syndrome. A corneoscleral patch graft was performed, followed by immunosuppression including oral cyclosporin and topical prednisolone. During a follow-up period of 12 months, the corneoscleral graft was well maintained with no recurrence

The role of PET/CT in Cogan’s syndrome

We report on the case of a 60-year-old woman with complaints of fatigue, coughing, anorexia, atypical chest pain, recurrent fever, and also ear pain and hearing loss. A test for anti-neutrophil cytoplasmic antibody (ANCA) was myeloperoxidase positive with p-ANCA specificity. Laboratory acute phase parameters were increased. A 2-deoxy-2-[18F]fluoro-d-glucose positron emission tomography/computed tomography investigation showed pathological uptake in the aorta ascendens, with no other involvement of the large vessels. After therapy with methylprednisolon intravenously and later prednisolon orally with methothrexate, her general condition and hearing loss improved both subjectively and objectively. “Atypical” Cogan’s syndrome was diagnosed on the basis of sensorineural deafness with improvement on steroids and large-vessel vasculitis of the aortic arch

A genetic variant in CDKN2A/2B locus was associated with poor prognosis in patients with 1 esophageal squamous cell carcinoma

Esophageal squamous cell carcinoma (ESCC) is among the leading causes of cancer related death. Despite extensive efforts in identifying valid cancer prognostic biomarkers, only a very small number of markers have been identified. Several genetic variants in the 9p21 region have been identified that are associated with the risk of multiple cancers. Here, we explored the association of two genetic variants in the 9p21 region, CDKN2A/B, rs10811661 and rs1333049 for the first time in 273 subjects with, or without ESCC. We observed that patients with ESCC had a higher frequency of a TT genotype for rs10811661 than individuals in the control group, and this polymorphism was also associated with tumor size. Moreover, a CC genotype for the rs1333049 polymorphism was associated with a reduced OS of patients with ESCC. In particular, patients with a CC (rs1333049) genotype had a significantly shorter OS (CC genotype: 34.5±8.9 months vs. CG+GG: 47.7±5.9 months; p value= 0.03). We have also shown the association of a novel genetic variant in CDKN2B gene with clinical outcome of ESCC patients. Further investigations are warranted in a larger population to explore the value of emerging markers as a risk stratification marker in ESCC. Key word: Esophageal squamous cell carcinoma, risk marker, CDKN2A/B, polymorphis

A genetic polymorphism in the CYP1B1 gene in patients with squamous cell carcinoma of the esophagus: an Iranian Mashhad cohort study recruited over 10 years

Background: Esophageal-cancer is the seventh most common-cause of cancer-related-deaths in men. Cytochrome-P450-family-1-subfamily-B-polypeptide-1 (CYP1B1) plays a role in the metabolism of xenobiotics, and is associated with several cancers. Here we investigated the association between a genetic-variant, CYP1B1-rs1056836, with the clinical-characteristics of patients with esophagus-squamous-cell-carcinoma (ESCC). Method: 117-patients with ESCC and 208 healthy-subjects were recruited. DNA was extracted and genotyped. Kaplan-Meier curves were utilized to assess overall and progression-free survival. The relationship between clinicopathological-data, disease-prognosis, and survival, were evaluated with the genotypes. Results: the genotypic frequency for GG, GC, and CC were 58.6%, 29.8%, 11.5% respectively in the healthy subjects and 51.8%, 36.14% and 12% in the ESCC group. An association between the GG genotype and stage of ESCC was found. Conclusion: Our findings suggest a relationship between the CYP1B1-rs1056836 genetic polymorphism and clinical features of ESCC, supporting further studies in larger-populations in different-ethnic groups, taking into account potentially important environmental-factors

The potential utility of B cell-directed biologic therapy in autoimmune diseases

Increasing awareness of the importance of aberrant B cell regulation in autoimmunity has driven the clinical development of novel B cell-directed biologic therapies with the potential to treat a range of autoimmune disorders. The first of these drugs—rituximab, a chimeric monoclonal antibody against the B cell-specific surface marker CD20—was recently approved for treating rheumatoid arthritis in patients with an inadequate response to other biologic therapies. The aim of this review is to discuss the potential use of rituximab in the management of other autoimmune disorders. Results from early phase clinical trials indicate that rituximab may provide clinical benefit in systemic lupus erythematosus, Sjögren’s syndrome, vasculitis, and thrombocytopenic purpura. Numerous case reports and several small pilot studies have also been published reporting the use of rituximab in conditions such as myositis, antiphospholipid syndrome, Still’s disease, and multiple sclerosis. In general, the results from these preliminary studies encourage further testing of rituximab therapy in formalized clinical trials. Based on results published to date, it is concluded that rituximab, together with other B cell-directed therapies currently under clinical development, is likely to provide an important new treatment option for a number of these difficult-to-treat autoimmune disorders

Ameliorative Effect of Methanolic Extract of Broccoli (BMX) on Diclofenac Sodium (DIC)-Induced Oxidative Damage in Rat Kidney

Abstract Introduction: The objective of this study was to investigate the potential protective effect of the methanolic extract of broccoli against oxidative stress induced by diclofenac in rats. Non-steroidal anti-inflammatory drugs (NSAIDs) are known to cause nephrotoxicity, hence the need to explore the therapeutic potential of medicinal plants. Materials and methods: A total of 48 adult male Wister rats with a maximum age of 2-3 months with an average weight of 220 g were randomly divided into four equal groups (12 in each group The first group was control (C) and fed physiological saline without treatment, the second group was BC which treated with broccoli methanolic extract (BMX) at a dose of 500 mg/kg/Intraperitoneal injection, the third group was DC which treated with diclofenac sodium (DIC, 100 mg/kg, Intra-muscular injection), and the fourth group was BC plus DC which treated diclofenac sodium (100 mg/kg, Intra-muscular injection) and broccoli (500 mg/kg/ Intraperitoneal injection). After blood collection, serum was isolated, and urea, creatinine, interleukin-1, and TNF-α were measured in blood serum. In kidney tissue, malondialdehyde (MDA), superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) were measured. At the end of the study, the samples were taken for histopathological investigation. Results: The results of the present study indicated that diclofenac sodium causes severe kidney damage. The levels of creatinine and urea showed a significant increase in the DC group compared with the control and other treatment groups. The pro-inflammatory biomarkers in blood serum increased in the DC group and significantly decreased in the BC+DC group compared with control and other treatment groups. These changes were in line with the significant decrease of GPx and CAT enzyme levels in the DC group and its increase in the BC group. Malondialdehyde increased in the DC group and reached its lowest level in the BC group. Hyperemic changes, accumulation of inflammatory cells, and bleeding were indicators of diclofenac tissue poisoning reported in the kidney. https://jlar.rovedar.com/index.php/JLAR/article/view/