Biomedical Research and Therapy

Study on gene expression of IL-17A in eutopic and ectopic tissue sample of endometriosis patients and comparison with control group

Fakhri Hoseininasab — 2024-06-30

Introduction: The growth of endometrial tissue beyond the uterine cavity characterizes endometriosis, a chronic inflammatory disease. IL-17A, along with other immune mediators and a myriad of immune cells including Th17 lymphocytes and macrophages, are more prevalent in the peritoneal fluid of patients with endometriosis. IL–17A facilitates the implantation of endometrial tissue in ectopic locations by inducing growth factors and inflammatory cytokines from other immune cells. This work focuses on the levels of IL-17A gene expression in tissue samples from patient and control groups, as prior research has not extensively covered the gene expression of inflammatory mediators in tissue samples.

Methods: This study is both experimental and case-control in nature. Tissue samples were collected from 32 women undergoing laparoscopy at Yazd Shahid Sadoughi Hospital. The samples were divided into two groups: 16 patients with endometriosis and 16 healthy individuals. Within the patient group, there were two types of samples: eutopic and ectopic. The expression of IL-17A was assessed with RT-qPCR.

Results: RT-qPCR results showed a significant difference in IL-17A gene expression between ectopic lesions and eutopic samples from endometriosis patients (P value < 0.0001). Additionally, there was a significant increase in gene expression in eutopic samples from endometriosis patients compared to control samples (P value = 0.0176).

Conclusion: This study confirms the crucial involvement of inflammatory mediators like IL-17A in endometriosis through molecular findings in tissue samples, reflecting the elevated IL-17A content in the eutopic endometrium and ectopic lesions of endometriosis patients.

The value of hematological indices as predictors of septic shock in acute obstructive pyelonephritis

Minh Hoang Truong — 2024-06-30

Introduction: Acute Obstructive Pyelonephritis (AOP) is a severe and prevalent infection within the urinary system, prone to rapidly escalate into urosepsis and potentially result in septic shock, which poses a significant mortality risk. This study investigates the potential of certain blood parameters to serve as indicators for predicting the likelihood of developing septic shock in AOP patients.

Methods: We conducted a retrospective cohort study involving 60 patients who were diagnosed with AOP as a result of urinary tract stones or benign ureteral strictures, enrolled from August 2023 to February 2024. Key hematological data, including white blood cell count, neutrophil, lymphocyte, and platelet levels, as well as ratios such as neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR), alongside the systemic immune-inflammation index (SII), were extracted from complete blood counts recorded at hospital admission. These parameters were analyzed using univariate and multivariate logistic regression models to assess their predictive value for septic shock.

Results: The analysis revealed that 22 out of 60 participants (36.7%) progressed to septic shock following AOP. Notably, the likelihood of septic shock was higher in patients with diabetes mellitus (DM) (p = 0.037), those with diminished lymphocyte (p = 0.043) and platelet counts (p < 0.001), and elevated neutrophil-to-platelet ratio (p = 0.049) when compared to the non-septic shock cohort. Furthermore, multivariate logistic regression identified DM, NLR ≥ 8.7 (OR = 12.529, p = 0.030), and platelet counts below 150 x 109/L (OR = 4.375, p = 0.049) as independent predictors of septic shock.

Conclusion: Elevated NLR, reduced platelet count, and the presence of DM are significant predictors for the development of septic shock in patients afflicted with AOP. These findings suggest that closer monitoring and management of these parameters could be crucial in the early identification and treatment of patients at higher risk of septic shock.

Exploring the Effect of Phytochemical Extract (Benincasa sp.) on the Inflammatory Mediators and Regulatory Pathways of Acute Cisplatin Nephrotoxicity in Pre-clinical Mouse Model

Payal Pal — 2024-06-30

Introduction: Cisplatin-induced acute nephrotoxicity is typically manifested by a decrease in kidney function, electrolyte imbalances, and acute kidney injury (AKI). Most therapies for AKI are costly and have serious side effects. Utilizing phytotherapy for the prevention of kidney disease has the potential to reduce both treatment expenses and the occurrence of associated side effects. Benincasa cerifera (BC) offers extensive advantages owing to its anti-inflammatory, antioxidant, and anti-diabetic characteristics. This study aims to demonstrate the protective effects of BC on the inflammatory mediators and regulatory pathways in a cisplatin-induced acute kidney injury (AKI) model.

Methods: Fifteen 6–8-week-old female BALB/c mice (weighing 20-25 g) were divided into three groups as follows: (I) Control, (II) Cisplatin, (III) Cisplatin + BC. The disease was induced with a single dose (15 mg/kg) of cisplatin on day 0, followed by treatment with an ethanolic extract of BC (500 mg/kg). On day 7, the sacrificed mice were used to study the histopathological, biochemical, immunological, and inflammatory parameters.

Results: Treatment with BC successfully restored the clonogenic potential of the kidney, blood, spleen, and bone marrow cells. Flow cytometry showed that cisplatin-induced abnormalities in cellular circulation and the migration of CD45⁺B220⁺ B cells, CD4⁺, CD8⁺ T lymphocytes, and F4/80⁺ cells in the blood were significantly recovered with the treatment of BC. This study also found that BC inhibited the upregulation of different inflammatory cytokines, which were involved in the Th₁, Th₂, and Th₁₇ response.

Conclusion: Phytochemical-based novel treatment strategies developed from this work will provide safe options for patients and assist in reducing the disease burden of AKI.

Significant Associations Between Age, Menstrual Status, and Histopathological Types of Cervical Carcinoma in Vietnamese Patients: Insights from a Retrospective and Prospective Analysis

Hung Van Pham — 2024-06-30

Introduction: Cervical cancer, predominantly associated with high-risk Human Papillomavirus (HPV) types 16 and 18, presents a substantial public health challenge, particularly impacting women in low and middle-income countries. This study aims to address a vital knowledge gap by examining the relationship between age, menstrual status, and histopathological types of cervical carcinoma in Vietnamese patients.

Methods: The research was conducted at a major provincial public maternity and pediatric hospital in Vietnam from August 2019 to July 2022. A total of 48 adult female patients with histopathologically confirmed invasive cervical carcinoma were included in this combined retrospective and prospective observational study. Demographic and clinical data were collected and analyzed using univariate analysis to determine the associations between different factors and histopathological types. Statistical significance was set at p < 0.05, with odds ratios (ORs), 95% confidence intervals (CIs), and p-values calculated accordingly.

Results: The results revealed that squamous cell carcinoma (SCC) was the most common histopathological type (81.2%), followed by adenocarcinoma (12.5%) and adenosquamous carcinoma (6.2%). Within the SCC subtype, non-keratinizing SCC was the most prevalent (69.2%). Individuals aged 50 years and older had significantly higher odds of being diagnosed with SCC compared to those aged 39 years or younger (OR = 10.40, 95% CI: 1.48-73.00, p = 0.02). Menopausal individuals also had significantly increased odds of SCC compared to those who were menstruating (OR = 10.35, 95% CI: 1.18-90.95, p = 0.04).

Conclusion: These findings underscore the significant correlations between age, menstrual status, and the prevalence of SCC in Vietnamese patients, underscoring the importance of targeted public health initiatives. The study provides crucial insights that could inform the development of effective prevention and management strategies in Vietnam and similar settings.

Methanol extract from Apium graveolens stimulate glucagon-like peptide-1 secretion (GLP-1), reduced dipeptidyl-peptidase-4 (DPP-4) and protect pancreatic b cells against glucotoxicity and H2O2 toxicity

Rosa Martha Pérez Gutiérrez — 2024-06-30

Introduction: Glucagon-like peptide-1 (GLP-1) plays a critical role in glucose regulation by stimulating insulin secretion in a glucose-dependent manner. It enhances the functionality of pancreatic β-cells, minimizing apoptotic signals while promoting their proliferation and neogenesis. Consequently, leveraging plant-based GLP-1 agonists offers a promising approach to mitigating hyperglycemia in individuals with type 2 diabetes. This study aimed to explore the potential of methanol extract from Apium graveolens (commonly known as celery) to enhance insulin secretion, inhibit dipeptidyl peptidase-4 (DPP-4), and boost GLP-1 levels. Furthermore, it assessed celery's ability to protect pancreatic β cells against glucotoxicity and H₂O₂-induced toxicity in vitro. Additionally, we sought to identify the flavonoids present in the crude ethanolic extract of celery through HPLC/MS analysis.

Methods: We assessed cell viability, cell integrity (using lactate dehydrogenase (LDH) leakage assay), mitochondrial function (via ATP production), and insulin secretion in INS-1 pancreatic β-cells. GLP-1 activation and insulin sensitivity were evaluated in GLUTag cells, while DPP-4 activity was measured using an in vitro inhibitory assay.

Results: HPLC/MS analysis revealed the presence of 11 phenolic compounds in celery. Treatment with varying concentrations of celery extract (100, 125, 150, 200 µg/mL) resulted in decreased cell death, significantly improved cell viability, and increased cellular ATP levels, thereby offering protection against glucotoxicity and H₂O₂-induced toxicity. Additionally, it boosted insulin production and reduced insulin resistance. The inhibitory effect of celery extract on DPP-4 activity, coupled with the increase in GLP-1 halflife, enhances insulin secretion from β cells, outlining celery's potential hypoglycemic mechanism.

Conclusion: The findings of this study underscore celery's therapeutic potential as a treatment option for individuals with type 2 diabetes, attributing to its ability to modulate insulin secretion, enhance pancreatic β-cell survival, and inhibit DPP-4, thereby increasing GLP-1 levels. This illuminates a promising avenue for further research and potential diabetes management strategies.

Eosinophilic Gastrointestinal Disease Presenting as Chronic Diarrhea: A Case Report

Nhan Trung Phan — 2024-06-30

Eosinophilic gastrointestinal diseases (EGIDs) constitute a spectrum of disorders distinguished by the abnormal infiltration of eosinophils into the walls of the gastrointestinal tract, a phenomenon that frequently results in delayed or overlooked diagnoses due to the nonspecific nature of symptoms and endoscopic findings. This article discusses a noteworthy case characterized by chronic diarrhea and mild abdominal discomfort. The presence of peripheral eosinophilia and the evidence obtained from biopsies raised suspicions, ultimately leading to the diagnosis of EGIDs. Despite a two-month diagnostic delay attributed to limited disease awareness, the patient responded well to medical management. The therapeutic regimen comprised methylprednisolone, ketotifen, and montelukast, complemented by dietary modifications, culminating in the full resolution of symptoms. A notable complication was the onset of severe cellulitis during steroid treatment, necessitating an expedited reduction in the steroid dosage while continuing with other medications and undertaking surgical debridement. This infection was successfully controlled, and the corticosteroid therapy was gradually tapered off and discontinued over an eight-week period. The administration of ketotifen and montelukast was maintained, with no further recurrences reported. This case exemplifies the critical need to consider EGIDs in the differential diagnosis of individuals presenting with gastrointestinal symptoms, particularly when peripheral eosinophilia is evident. Furthermore, it emphasizes the imperative of holistic patient care, inclusive of managing infectious complications that may arise during the course of treatment.

A novel KIF11 missense mutation causing Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR): A case report and literature review

Samira Asadollahi — 2024-06-30

Introduction: Microcephaly with or without chorioretinopathy, lymphedema, or mental retardation (MCLMR) is an autosomal dominant rare syndrome. The characteristic features include microcephaly, eye disorders, and mild-to-moderate intellectual disability. Recent evidence has revealed that mutations in the kinesin family member 11 (KIF11) gene are associated with MCLMR.

Methods: Herein, we present the case of a four-year-old Iranian girl with clinical manifestations of MCLMR and a literature review of previous cases with attributes of MCLMR. Considering her developmental delay, microcephaly, small face, low-set ears, hearing loss, visual defects, and seizures, MCLMR was suspected, and whole-exome sequencing (WES) was performed. The candidate variant was screened in the proband, her parents, and other family members using Sanger sequencing. The variant's pathogenicity and the effect of amino acid substitution on protein stability and 3D structure were evaluated by in silico analysis and different bioinformatics prediction tools.

Results: The WES analysis identified a de novo novel heterozygous missense mutation in the KIF11 gene [c.629T>C; p.(Val210Ala)], which co-segregated with the phenotype and was consistent with autosomal dominant inheritance. According to in silico protein analysis results, the mutation occurred in the kinesin motor domain, specifically in the BimC/Eg5 spindle pole proteins, that participate in spindle assembly and chromosome segregation during cell division. It had a negative effect on the protein structure and led to a loss of protein function.

Conclusion: The pathogenic mutation in the KIF12 gene could reduce protein activity and lead to the pleiotropic phenotypes of MCLMR syndrome in our patient. To our knowledge, this variant has not been reported previously in the literature, and this report is the first genetic study of an Iranian patient suffering from MCLMR with the novel KIF11 variant. Also, our findings broaden both the understanding of the clinical phenotype and the allelic repertoire of KIF11. Comparing the patient's features with those of other patients reported previously provides future viewpoints for clinical study in this area.