Interleukin-17-mediated protective cytokine signaling against degeneration of the retinal pigment epithelium.

Injuries to the retinal pigment epithelium (RPE) and outer retina often result in the accumulation of retinal microglia within the subretinal space. These subretinal microglia play crucial roles in inflammation and resolution, but the mechanisms governing their functions are still largely unknown. Our previous research highlighted the protective functions of choroidal γδ T cells in response to RPE injury. In the current study, we employed single-cell RNA sequencing approach to characterize the profiles of immune cells in mouse choroid. We found that γδ T cells were the primary producer of interleukin-17 (IL-17) in the choroid. IL-17 signaled through its receptor on the RPE, subsequently triggering the production of interleukin-6. This cascade of cytokines initiated a metabolic reprogramming of subretinal microglia, enhancing their capacity for lipid metabolism. RPE-specific knockout of IL-17 receptor A led to the dysfunction of subretinal microglia and RPE pathology. Collectively, our findings suggest that responding to RPE injury, the choroidal γδ T cells can initiate a protective signaling cascade that ensures the proper functioning of subretinal microglia.

A comprehensive analysis of selected medicines collected from private drug outlets of Dhaka city, Bangladesh in a simple random survey.

Comprehensive data are needed to prevent substandard and falsified (SF) medicines as they pose a major risk to human health. To assess the quality of selected medicines, samples were collected from random private drug outlets of Dhaka North and South City Corporation, Bangladesh. Sample analysis included visual observation of the packaging, authenticity of the samples, legitimacy and registration verification of the manufacturer, physicochemical analysis, and price. Chemical analysis of the samples was performed using a portable Raman spectroscopy and high-performance liquid chromatography according to the pharmacopoeia. Several discrepancies were noted in the visual observation of samples. Among the 189 collected samples of esomeprazole (ESM), cefixime (CFIX), and amoxicillin-clavulanic acid (CVA-AMPC), 21.2% were confirmed to be authentic, 91.3% manufacturers were confirmed legitimate, and 2.1% of all samples were unregistered. Chemical analysis of the samples revealed that 9.5% (95% CI 5.7-14.6) of samples were SFs. Falsified samples and quality variation in the same generic branded samples were both detected by Raman spectroscopic analysis. Overall, sample prices were satisfactory relative to the international reference price. This study documents the availability of poor-quality medicines, demonstrating the need for immediate attention by the national medicine regulatory authority.

Evaluation of serum amino acids and non-enzymatic antioxidants in drug-naïve first-episode major depressive disorder.

BACKGROUND: The alterations of biological markers are thought to be effective tools to understand the pathophysiology and management of major depressive disorder (MDD). A lot of researches has implied many markers for depression, but any of them fully discovered the association between the markers and depression. The present study investigated the serum levels of amino acids and non-enzymatic antioxidants in major depression, and also explained their association with depression. METHODS: This study examined 247 MDD patients and 248 healthy controls (HCs) matched by age and sex. The Hamilton Depression Rating Scale (Ham-D) was used to all the participants to measure the severity of depression. Quantification of serum amino acids, vitamin A and E were carried out using the HPLC system whereas vitamin C levels were measured by UV-spectrophotometer. All the statistical analysis was performed by SPSS statistical software (version 23.0). The independent sample t-test, the Mann-Whitney U test, and the Fisher's exact test were applied to detect the group differences where a Bonferroni correction applied to the p value. RESULTS: It was observed that serum levels of four amino acids (methionine, phenylalanine, tryptophan, and tyrosine) along with three non-enzymatic antioxidants (vitamin A, E, and C) were significantly dropped in MDD patients compared to HCs (Cohen's d (d): - 0.45, - 0.50, - 0.68, - 0.21, - 0.27, - 0.65, and - 0.24, respectively). Furthermore, Ham-D scores of cases were negatively correlated with serum levels of methionine (r = - 0.155, p = 0.015) and tyrosine (r = - 0.172, p = 0.007). CONCLUSION: The present study suggests that lowered serum methionine, phenylalanine, tryptophan, tyrosine, and non-enzymatic antioxidants are associated with depression. The reduction of these parameters in MDD patients may be the consequence, and not the cause, of major depression.

Evaluation of Serum Interleukin-6 and C-reactive Protein Levels in Drug-naïve Major Depressive Disorder Patients.

Background Major depressive disorder (MDD) is a disabling health problem with a very high global prevalence and burden. Alteration of inflammatory markers in depression is of growing interest to many psychiatry researchers. This study aimed to examine the serum levels of interleukin-6 (IL-6) and C-reactive protein (CRP) in MDD patients to find out their association with depression. Materials and methods The present study recruited 88 MDD patients and 86 control subjects matched by age, gender, and body mass index (BMI). The Hamilton depression rating scale (Ham-D) was used on all patients to measure their severity of depression. Serum levels of IL-6 and CRP were analyzed by commercially available enzyme-linked immunosorbent assay (ELISA) kits (Abcam, Cambridge, MA, USA). Results The mean values of serum levels of IL-6 and CRP were 2.94 ± 0.12 pg/mL and 0.99 ± 0.02 mg/L for the patient group and 2.42 ± 0.21 pg/mL and 1.09 ± 0.06 mg/L for the control group, respectively. We found significantly elevated concentrations of serum IL-6 in MDD patients compared with control subjects (p < 0.001). However, the alteration of serum CRP levels was not significant between the groups (p = 0.126). Ham-D scores of patients were positively correlated with serum IL-6 (r = 0.552; p = 0.004) and CRP (r = 0.621; p < 0.001) levels. Moreover, serum IL-6 and CRP levels were observed to be positively correlated (r = 0.452; p = 0.043) with each other in depression. Conclusions The present study suggests that increased serum IL-6 level might be a contributing factor to the pathogenesis of depression.

Ethnopharmacological survey of medicinal plants used by traditional healers and indigenous people in chittagong hill tracts, bangladesh, for the treatment of snakebite.

Snakebites are common in tropical countries like Bangladesh where most snakebite victims dwell in rural areas. Among the management options after snakebite in Bangladesh, snake charmers (Ozha in Bengali language) are the first contact following a snakebite for more than 80% of the victims and they are treated mostly with the help of some medicinal plants. Our aim of the study is to compile plants used for the treatment of snakebite occurrence in Bangladesh. The field survey was carried out in a period of almost 3 years. Fieldwork was undertaken in Chittagong Hill Tracts, Bangladesh, including Chittagong, Rangamati, Bandarban, and Khagrachari. Open-ended and semistructured questionnaire was used to interview a total of 110 people including traditional healers and local people. A total of 116 plant species of 48 families were listed. Leaves were the most cited plant part used against snake venom. Most of the reported species were herb in nature and paste mostly used externally is the mode of preparation. The survey represents the preliminary information of certain medicinal plants having neutralizing effects against snake venoms, though further phytochemical investigation, validation, and clinical trials should be conducted before using these plants as an alternative to popular antivenom.