Biomedical Research and Therapy

Up-regulation of miR-485-3p in Iranian patients with relapsing-remitting multiple sclerosis by targeting HLADRB1

Maryam Fotouhi Firouzabad — 2024-10-31

Background: Multiple sclerosis (MS) is an autoimmune disease characterized by chronic inflammation in the central nervous system (CNS). MicroRNAs (miRNAs) are tiny molecules that act as regulators within cells, influencing various processes linked to diseases like MS. Understanding the specific role of miRNAs in MS is crucial for developing new treatment strategies. This study focused on an Iranian population with relapsing-remitting MS. The researchers aimed to examine the levels of a particular miRNA, miR-485-3p, and its target gene, HLADRB1, over a minimum two-month period. By investigating these molecules, the study sought to shed light on the potential involvement of miR-485-3p in the pathogenesis of MS.

Methods: This study investigated the relationship between miR-485-3p and relapsing-remitting multiple sclerosis (RRMS) using a case-control design. The researchers analyzed the expression levels of both miR-485-3p and its potential target gene, HLADRB1, in peripheral blood mononuclear cells (PBMCs) collected from participants. The study included 90 individuals: 30 diagnosed with RRMS who were experiencing a relapse, 30 diagnosed with RRMS who had been in a relapse state for at least two months, and a control group of 30 healthy subjects.

Results: The expression of miR-485-3p was different in the two groups studied (P < 0.0002 and P < 0.001, respectively). RRMS patients in relapse and those at least two months post-relapse showed increased expression compared to the normal group. Additionally, we found increased expression of HLADRB1 in RRMS patients compared to healthy control subjects (P < 0.0001 and P < 0.0003, respectively).

Conclusion: According to the study's findings, miR-485-3p, at least in the Iranian population studied, is likely to be an important biomarker for the early diagnosis of RRMS. However, HLADRB1 might be a crucial target for the development of this illness. Nevertheless, more research is required to provide a definitive answer.

Relationship between Covid-19 pneumonia intensity with lymphopenia and CRP levels

Maryam Panahi — 2024-10-31

Introduction: COVID-19 is a highly contagious and deadly disease. However, there is no accurate diagnostic test to predict its severity. The aim of this study was to determine the relationship between the lymphocyte counts and CRP levels and the severity of pulmonary involvement shown in the CT scan of the patients with pneumonia caused by COVID-19.

Methods: In this cross-sectional study, demographic information and laboratory findings of the patients with COVID-19 were collected. Then, each patient's pulmonary involvement was scored based on the CT scan results. The data were analyzed using SPSS 16 software as well as ANOVA, chi-square test, Pearson correlation coefficient, and ROC curve.

Results: Data of 125 COVID-19 patients with the mean age of 59.37 ± 1.5 showed that the prevalence of lymphocytes < 1100 × 10⁹/L and CRP > 100 mg/L was higher in the patients with severe pulmonary involvement than in those with mild involvement (p < 0.001). Furthermore, an increase in pulmonary involvement severity observed in HRCT led to decreased absolute blood lymphocyte count and increased CRP levels (p < 0.001). The CRP test with an area under the ROC curve of 0.76 could be an acceptable test for predicting the severity of pulmonary involvement in patients with pneumonia caused by COVID-19.

Conclusion: It was found out in this study that there was a significant positive correlation between CRP levels and the severity of COVID-19 pneumonia. The CRP test could also be an acceptable test for predicting the severity of pulmonary involvement in COVID-19.

Methylation of HPV-16 and HPV-18 E6 promoter CpG sites in women with abnormal pap smears

Somayeh Haddadi — 2024-10-31

Introduction: HPV-16 and HPV-18 account for around 70% of cases of invasive cervical cancer worldwide. These are highly pathogenic and high-risk genotypes. The most prevalent sexually transmitted disease is human high-risk papillomavirus (HR-HPV), which can infect anyone who engages in sexual activity at any time in their life. To evaluate the possibility that the virus causes malignant lesions in infected women with high-risk HPV types who have normal and abnormal Pap smears, the current study examined the methylation pattern of CpG islands in the oncogene promoter of high-risk HPV E6.

Methods: Forty-eight Pap smears were collected from women referred to Shahid Sadoughi Hospital in Yazd for this case-control study. The Sinaclon kit was used for DNA extraction. PCR amplification with specific primers allowed the identification of HPV-16 and HPV-18 types. The bisulfite modification method, based on the EpiTect Bisulfite Conversion Kit, was then used to identify methylation in the E6 gene. Version 22 of the SPSS program was used to collect the data, and the corresponding statistical tests were used for analysis.

Results: In this study, methylation at position 506 in the HPV-16 E6 gene was detected in 10.4% (n = 5/48) of cases; however, methylation in the 1985 region for the E6 promoter of HPV-18 was 20.8% (n = 10/48). Comparison of the methylation rate in the HPV-18 nucleotide 1985 in normal and abnormal Pap smear samples showed that the methylation rate in normal and abnormal samples was 55.8% and 44.2%, respectively. There was no significant difference between the frequency of HPV-18 and HPV-16 DNA methylation in all selected CpG nucleotide regions (P ≥ 0.05).

Conclusion: Our results indicate that the methylation change in the E6 gene promoter was not involved in the development of infection with HPV-16 and HPV-18 types in the study population.

Three-dimensional culture model of urothelial carcinoma cell lines: current advances, challenges and future perspective

Siti Farizan Mansor — 2024-10-31

Despite the high number of cases reported, studies describing the pathogenesis of urothelial carcinoma (UC) remain limited. This is due to insufficient in vivo models that can accurately recapitulate the pathogenesis of UC recurrence and elucidate the involvement of the tumour microenvironment (TME) during carcinogenesis. Models of cancer pathomechanism in monolayer culture provide inaccurate resemblance due to biophysical and chemical changes. In simplified 2D culture conditions, factors such as tissue architecture, cell-to-cell and cell-to-matrix interaction, and mechanical and biochemical networks, all of which are involved in drug response, are lost. Three-dimensional (3D) culture of clinical biopsy is considered an ideal model to understand UC pathogenesis, the role of the microenvironment, and mechanical adaptations due to improved translational capacity. However, limited biopsies and challenges in primary cell culturing have shifted researchers towards developing cell line-based 3D culture in the pursuit of pathomechanism exploration. A comprehensive literature evaluation was carried out by searching the PubMed, Scopus, and Web of Science databases from January 2000 to May 2022. The initial search yielded 525 articles, and 195 studies were selected based on the inclusion and exclusion criteria. This review highlights recent challenges, future strategies, and the clinical implications of developing high-throughput, cell line-based 3D models for personalized UC treatment, a critical gap in the current literature.

Moringa seeds mitigate oxidative stress and promote antioxidant activity in aging male rats

Noha Sayed Hamed — 2024-10-31

Introduction: The aim of this study was to examine the antioxidant effects of one of the natural plant sources against oxidative stress caused by aging. Moringa oleifera seeds (MOS), the less utilized part, were chosen to investigate their role against oxidative stress in aging male albino rats.

Methods: DPPH (2,2-diphenyl-1-picryl-hydrazyl-hydrate), ABTS (2,2'-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid)), polyphenols, some vitamins, and amino acids were estimated in the moringa seeds. The animals were mainly divided into two groups: adult and elderly rats. Each group was further subdivided equally into normal (not treated) and treated rats (which were orally administered an aqueous ground suspension of the MOS seeds) at a dose of 500 mg/kg body weight for four weeks (five days/week). Serum levels of free testosterone, free triiodothyronine (FT3), free thyroxine (FT4), and liver and kidney function were assessed. Additionally, histopathological investigations of brain and testicular tissue samples were conducted. Glutathione S-transferase (GST), malondialdehyde (MDA), and acetylcholinesterase (AChE) were measured in the homogenates of brain and testicular tissues.

Results: The results reveal a powerful antioxidant effect of MOS, indicated by a significant reduction in MDA levels along with a significant increase in GST and AChE concentrations. MOS treatment significantly increased serum testosterone levels and thyroid hormone levels in the male rats' serum.

Conclusion: MOS could improve most oxidative stress disorders associated with aging in male rats. Finally, the inadequacy of research on brain and testicular aging has been identified, and new research options have been proposed to aid in the treatment of brain and testicular aging. Further study in this area may uncover the underlying mechanisms, paving the way for the development of new treatments for age-related issues.

Safety and Efficacy of Combined Oral Misoprostol and Foley Catheter Treatment in Comparison with Oral Misoprostol Alone for Labor Induction: A Randomized Clinical Trial study

Shima Beyrami — 2024-10-31

Background: In the context of a rising trend in labor induction cases, limited research has explored the efficacy of the simultaneous use of misoprostol and Foley catheter methods. This clinical trial investigates the efficacy and safety of combining these labor induction techniques compared to the use of oral misoprostol alone.

Methods: This randomized, open-label clinical trial was conducted on pregnant women candidates for induction of labor due to various medical indications referred to Shariati Hospital, Tehran. The oral misoprostol plus Foley catheter group received 50 mg of oral misoprostol every 4 hours, along with the insertion of a Foley catheter into the cervix under sterile conditions. The comparison group received only oral misoprostol. The Bishop scores in this study were measured prior to induction, and at 6 hours and 12 hours after the initiation of the intervention by a single specialist. Statistical comparisons included the number of deliveries within 24 hours, Bishop score, oxytocin dosage, and maternal and fetal complications.

Results: The two groups were homogeneous in regard to age (27.11 ± 3.88 vs. 26.46 ± 4.95, P=0.26), gestational week (P = 0.44), and BMI (P = 0.88). The combination of the Foley catheter and oral misoprostol group showed significantly higher Bishop scores at 6 hours (P < 0.001) and 12 hours (P = 0.02). The oral misoprostol alone group exhibited a significantly higher rate of cases failing to deliver within 24 hours of induction compared to the combination treatment group (73.4% vs. 11.6%, P < 0.001). Furthermore, the oral misoprostol alone group demonstrated significantly higher incidences of adverse outcomes, including uterine tachysystole (17.6% vs. 3.85%, P < 0.001), NICU hospitalization (8% vs. 1.54%, P = 0.015), abnormal Apgar score at five minutes (4.8% vs. 0%, P=0.01), and meconium presence (7.2% vs. 1.54%, P = 0.03).

Conclusion: This study suggests that the combined method for labor induction is more appropriate due to its quicker and more impactful results, along with lower complication rates.

Inhibiting autophagy does not decrease drug resistance in breast cancer stem-like cells under hypoxic conditions

Bui Dinh Khan — 2024-10-31

Introduction: Breast cancer has been one of the most frequently diagnosed cancers in women over the past decade. The presence of a breast cancer stem cell (BCSC) population within breast tumors significantly contributes to malignancy and drug resistance. Under the hypoxic conditions of breast tumors, BCSCs exhibit increased resistance to chemotherapy, complicating treatment and reducing its efficacy. Consequently, targeting BCSCs is considered a crucial strategy for breast cancer treatment. We hypothesize that the chemotherapy resistance of BCSCs is dependent on the upregulation of autophagy triggered by hypoxia. This study aims to investigate the relationship between autophagy and drug resistance of BCSCs in hypoxic conditions.

Methods: BCSCs were isolated from Vietnamese breast cancer cell line 1 (VNBRCA1) based on expression of CD44 and CD24. Cobalt (II) chloride (CoCl₂) was used to simulate a hypoxic environment in monolayer cell cultures. The hypoxic status of BCSCs was confirmed by the upregulation of the HIF-1α gene. Autophagy activation was assessed through the expression of autophagy-related genes (LC3B, Beclin-1, AMPK, PI3K, AKT). Drug resistance was evaluated by measuring the expression of ABCC10 and assessing cell proliferation under cisplatin treatment.

Results: The study revealed that CoCl₂ treatment led to high expression of HIF-1α and significant upregulation of LC3B in BCSCs, together with enhanced expression of ABCC10. Consequently, BCSCs exhibited marked resistance to cisplatin in the hypoxic environment. However, inhibition of autophagy using the autophagy inhibitor 3-methyladenine (3-MA) did not reduce cisplatin resistance in hypoxic conditions.

Conclusion: The findings indicate that in hypoxic conditions, BCSCs enhance both the autophagy process and drug resistance. However, the drug resistance of BCSCs in hypoxic conditions is not directly associated with the upregulation of autophagy. Therefore, targeting autophagy inhibition may not be an effective strategy to reduce drug resistance in hypoxia.

Severe haemolytic disease of foetus and new born due to Rhesus D alloimmunisation in highly sensitised Rhesus D negative pregnant woman

Mohd Nazri Hassan — 2024-10-31

Introduction: Severe hemolytic disease of the fetus and newborn (HDFN) due to red cell alloimmunization is a frequent cause of recurrent fetal loss. This condition becomes critical when standard treatments like intrauterine transfusion (IUT) or immune-modulating therapies such as therapeutic plasma exchange (TPE) and intravenous immunoglobulin (IVIG) are unavailable or not administered in a timely manner. This case report emphasizes the potential benefits of early TPE and IVIG administration.

Case Presentation: A 28-year-old Rhesus D (RhD) negative woman (G3P2) experienced recurrent fetal loss due to severe HDFN and had a history of RhD alloimmunization and fetal loss in her second pregnancy. In her third pregnancy, high anti-D titers (1:2,024) were identified at weeks 12 and 16. Despite the need, TPE and IVIG were not administered properly due to the patient missing follow-ups and the absence of IUT facilities, culminating in macerated intrauterine death (IUD) at 27 weeks.

Discussion: The failure to implement early TPE and IVIG interventions, alongside systemic treatment inadequacies, contributed to the adverse pregnancy outcome. This case accentuates the necessity of accessible and timely intervention in pregnancies complicated by high anti-D titers.

Conclusion: For RhD alloimmunized pregnancies with high anti-D titers, early administration of TPE and IVIG before 20 weeks of gestation is crucial in reducing fetal morbidity and mortality. This case underscores the importance of early intervention and continuous monitoring in managing sensitized pregnancies.