Volume 9 Issue 2 (2025): (in progress)

Gelsemium sempervirens (GS) extract is being used in phytomedicine and homeopathy for its anxiolytic properties but its mechanism of action is yet to be understood. Evidence from rodent models suggests existence of its high sensitivity to the central nervous system even in ultra‑diluted conditions. The diverse effects of its extract and/or its main alkaloids‑gelsemine, sempervirine, and koumine have been shown through different experiments in recent years. Sempervirine intercalates with DNA and inhibits topoisomerase‑I activity, which is thought to be a potential target for restricting viral replication during SARS‑CoV‑2 pathogenesis. Delta SARS‑CoV‑2 spike RBD,
the recombinant protein, was procured from Abclonal Pvt. Ltd. 14th‑day‑old Gallus gallus domesticus embryos were inoculated with RBD protein along with control alcohol in pre‑ and post‑treatment sets and challenged with Gelsemium 6CH, 30CH and 200CH potencies. After 48h, allantoic ϐluids were collected during harvesting and stored at −20 ℃ for the study of different cytokine gene expressions by RT‑PCR (Reverse Transcription Polymerase Chain Reaction). GS at 6CH, 30CH, and 200CH dilutions showed up‑regulation of IFN‑α and IL‑10 gene expressions in all experimental sets. Tendencies of down‑regulation of the genes were seen with TGF‑β1, IL‑1β, and IL‑6 cytokines, with few exceptions. IFN‑β and IL‑1β gene expression changes were relatively mild and mostly inconclusive. All expressions indicate a possible balancing effect between pro‑inϐlammatory and anti‑inϐlammatory cytokine gene expressions by Gelsemium. Ultra‑diluted GS in homeopathic doses can effectively modulate the expression of cytokine genes in SARS‑CoV‑2‑induced cytokine imbalance. Further studies are desired to understand its utility in clinical practice through structured clinical trials.

One of the causes of infertility and recurrent miscarriage is immunological factors or factors related to the immune system. Several immunological issues, for instance autoantibodies and alterations in the level of uterine immune cells, play a crucial role in immune-related infertility. This review evaluated all available immunological bases in female reproductive disorders, especially infertility and miscarriage to provide optimal diagnostic strategies for patients. NK cells are considered important elements of the innate immune system, ensuring that there is tolerance between the mother and child’s immune systems. Touching on the adaptive immune system, Th cells not only are able to impart directional structure on incoming lymphocytes draining from the periphery but also categorize into different subsets depending on where they are located within peripheral blood. During pregnancy, the immune system is skewed toward a type 2 T helper response, while fetal rejection is associated with a type 1 response The rules of organ transplantation require that the host’s immunological mechanisms, based on the incompatibility of antigens of the histocompatibility system, recognize the transplanted piece and ultimately reject it. Among the various therapeutic options, lymphocyte immunotherapy (LIT) stands out as a promising solution based on immunological principles. Some studies have shown that the success rate of LIT is 69%, but other studies have shown that the success rate has increased to 80%. On the other hand, controlled clinical trials are needed to further investigate immunomodulatory therapeutic strategies to help treat this disorder. Therefore, further studies are needed to achieve standardized diagnostic and immunological therapeutic approaches to increase the effectiveness of therapeutic interventions and increase the success rate of assisted reproductive technology (ART) cycles in these women.

The Notch1 signaling pathway is pivotal in neuroimmunomodulation and inflammation, and it significantly contributes to the development and pathogenesis of the nervous system. Consequently, targeting Notch signaling may offer a promising therapeutic approach for neurological disorders. In this investigation, we elucidated the crucial role of Notch1 signaling in neuronal apoptosis, immune regulation, and inflammatory signaling by knocking down the Notch1 gene in mouse hippocampal HT22 cells. Suppression of Notch1 resulted in a marked reduction in the expression of its downstream effector molecule Hes1, accompanied by a significant rise in apoptosis, increased levels of apoptosis-related proteins, and diminished cell viability. RNA sequencing analyses further revealed that differential expression was closely linked to apoptosis, immune-regulatory pathways, and inflammatory signaling. Apoptosis serves as a critical mechanism for eliminating abnormal cells and can impact immune response balance by modulating immune cell activation and function. Notch1 signaling can indirectly affect the neuroimmune microenvironment by regulating neuronal apoptosis. Thus, targeting the Notch1 signaling pathway not only safeguards neuronal function by inhibiting apoptosis but also modulates immune cell activation and inflammatory responses, offering a novel strategy for the immunotherapy of neurodegenerative and cerebrovascular diseases. Comprehending this mechanism provides a crucial foundation for exploring Notch1 immunotherapy for these conditions. By precisely modulating Notch1 signaling, it is anticipated that future therapies can achieve the dual benefits of neuroprotection and immunomodulation, paving the way for innovative treatments for related diseases.

Rheumatoid arthritis (RA) is a systemic autoimmune disorder driven by aberrant cytokine-mediated signalling that perpetuates synovial inflammation and joint destruction. Baricitinib, an oral Janus kinase-1/2 inhibitor, offers a mechanism-based therapeutic option; however, comparative data clarifying its broader immunomodulatory advantages remain limited. We conducted a 24-week, multicentre, double-blind, randomised controlled trial to compare the efficacy and safety of baricitinib with the tumour-necrosis-factor inhibitor adalimumab and with placebo in adults with moderate-to-severe RA who had an inadequate response to conventional synthetic DMARDs. Three hundred participants were allocated equally (1:1:1) to once-daily baricitinib 4 mg, subcutaneous adalimumab 40 mg every other week, or matched placebo, all on stable methotrexate. Co-primary endpoints were (i) mean change from baseline in the Disease Activity Score using 28 joints and C-reactive protein (DAS28-CRP) and (ii) the proportion of patients achieving clinical remission (DAS28-CRP < 2.6) at week 24. Secondary outcomes included the Health Assessment Questionnaire-Disability Index (HAQ-DI), 36-Item Short-Form Survey (SF-36), radiographic progression via modified Total Sharp Score (mTSS), and comprehensive safety assessments. Baricitinib achieved a greater DAS28 reduction (−3.3 ± 0.9) than adalimumab (−2.9 ± 0.8) and placebo (−1.5 ± 0.7), with remission rates of 50%, 45%, and 20%, respectively. Baricitinib also produced superior improvements in HAQ-DI and SF-36 and curtailed radiographic progression versus placebo. Adverse events—predominantly mild upper-respiratory infections—were more frequent with baricitinib, yet serious events were comparable across groups.

Tuberculosis (TB) remains a significant global health burden, particularly in children, where immune responses play a crucial role in disease progression. The objective of this research was to analyze the relationship of vitamin D and IL-17 levels with the severity of pediatric TB. This observational analytic study was conducted at Dr. Saiful Anwar Hospital, Malang, involving 33 pediatric patients diagnosed with TB, divided into mild (n = 8), moderate (n = 18) and severe (n = 7) groups. Severity was determined using the score developed in this study. Vitamin D levels were measured using the Cobas c501 analyzer, and IL-17 levels were measured using the Human IL-17 ELISA Kit. While Vitamin D level was significantly lower in microbiologically confirmed patients (p = 0.038), it was not significantly different among severity groups (p = 0.799). Meanwhile, IL-17 levels were significantly higher in patients with more severe respiratory distress (p = 0.01), although the difference between severity groups was not statistically significant (p = 0.966). Furthermore, there was no correlation between vitamin D levels and IL-17 levels (r = 0.178, p = 0.322). These findings indicate the need for further research to explore vitamin D supplementation as an adjunctive therapy and to evaluate IL-17 as a biomarker for disease activity.

Nephroptosis (NP), which is marked by excessive movement of the kidneys, has attracted renewed attention due to advancements in imaging technology. This retrospective study aimed to determine the prevalence, demographics, and clinical characteristics of NP in Kyrgyzstan using ultrasound Doppler examinations. Data from 13,235 patients at the Salymbekov University Clinic Network were analyzed over a period of three years. NP was detected in 378 (2.9%), with a higher prevalence in females (79.4%) than in males (20.6%). The most affected age group  was 20–40 years (58.5%), and right-sided NP predominated (75.1%). The number of NP cases increased annually, suggesting improved detection or changing trends. Comorbidities were found present in 57.9% of patients, with lupus nephritis (LN) being the most common (16.4%). Multivariate logistic regression analysis indicated that sex was not a significant predictor of LN in patients with NP. Immunosuppressive therapy with prednisone and cyclophosphamide improved kidney function in patients with NP and LN, although persistent symptoms required additional management or surgery in some cases. This highlights the importance of early detection and multidisciplinary management of NP. This study provides insights into the epidemiological patterns and clinical implications of NP in Kyrgyzstan, emphasizing the need for targeted screening, standardized diagnostic criteria, and preventive strategies for high-risk groups.

Nephroptosis (NP) is characterized by abnormal downward displacement of the kidney, predominantly affecting young working women aged 20–45 years. This retrospective observational study aimed to investigate the epidemiology, clinical manifestations, and treatment outcomes of NP in the Kyrgyz Republic between 2010 and 2023. Data from 1824 patients diagnosed with NP in various healthcare institutions were analyzed. NP occurred more frequently in women (79.6%) than in men (20.4%), with Bishkek showing the highest occurrence at 51.4%. Between 2020-2023, the NP incidence increased by 2.8%, and the most common associated conditions were LN (18.5%), hypertension (17.9%), and dyslipidemia (15.7%). In 205 patients with NP and LN, immunosuppressant treatment with prednisone and cyclophosphamide improved kidney function (eGFR increased from 65.8 ± 9.2 to 81.1 ± 7.4 mL/min/1.73 m²; p < 0.01) and reduced proteinuria (from 2.9 ± 1.3 to 0.8 ± 0.4 g/day; p < 0.001) over 12 months. However, 17.5% of patients required surgical nephropexy due to ongoing symptoms. The rising incidence of NPs in Kyrgyzstan emphasizes the need for enhanced diagnostic methods and clinical awareness. The common occurrence of NP with LN highlights the need for multidisciplinary management. While immunosuppressive therapy is effective for NP with LN, some patients benefit from surgical nephropexy. Future studies are needed to assess outcomes and improve treatment strategies, especially in patients with autoimmune diseases.

Henoch-Schönlein purpura (HSP) is a systemic vasculitis characterized by purpura, joint pain, abdominal discomfort, and renal involvement in children. This study aimed to evaluate the homocysteine (Hcy) levels, polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) C677T and methionine synthase (MTR) A2756G genes, and immunological parameters in 183 patients with HSP. Hyperhomocysteinemia (HHcy) was found in 67.5% of patients, with 66.6% and 7.4% of patients with HHcy having MTHFR C677T heterozygosity and homozygosity, respectively. MTR A2756G polymorphisms were present in 44.4% of patients with HHcy. Patients with both HHcy and gene mutations experience more severe symptoms. Flow cytometry revealed reduced CD4 and CD8 antigen expressions in some patients. Serum cytokine analysis showed significantly higher IL-6 and TNF-α levels in patients with generalized HSP than in controls and those with cutaneous-articular HSP. Immunomodulatory treatments, such as cyclosporin A and rituximab, were effective in severe, treatment-resistant cases, reducing symptoms and inflammatory markers in these patients. This study highlights the importance of genetic, metabolic, and immunological assessments in guiding personalized treatment for HSP. Recommendations include measuring Hcy levels, genotyping for MTHFR C677T and MTR A2756G polymorphisms, immunophenotyping, and considering immunomodulatory treatments in cases that are severe.

Background: Early identification of high-risk sepsis patients is essential for timely intervention and improved survival. Prognostic biomarkers can support clinical decision-making by stratifying mortality risk and informing treatment choices. Sepsis remains a major global health challenge due to its complex management and high mortality rate. Presepsin, a soluble CD14 subtype (sCD14-ST), has emerged as a promising biomarker for sepsis prognosis, demonstrating superior predictive value compared to conventional markers like procalcitonin (PCT). This study aims to evaluate the prognostic significance of Presepsin in predicting mortality among sepsis patients. Methods: A prospective cohort study was conducted on 110 adult sepsis patients admitted to the ICU at Dr. Saiful Anwar Hospital, Malang, from November 2018 to October 2019. Patients were diagnosed using the Sepsis-3 criteria, and Presepsin levels were measured using the chemiluminescent immunoassay (CLIA) method. Survival analysis was performed using Kaplan-Meier curves, and hazard ratios (HR) were calculated through Cox regression. Results: The ROC analysis identified 17,085 pg/mL as the optimal Presepsin threshold for predicting mortality (AUC: 0.939, 95% CI: 0.897–0.982, p < 0.001). Patients with Presepsin levels ≥17,085 pg/mL had a significantly lower median survival (3 days) compared to those with lower levels (9 days) (HR 3.654, 95% CI: 1.978–6.752,  p < 0.001). Among patients with high Presepsin levels, 32 of 33 (96.9%) died, whereas only 28 of 77 (36.4%) patients with lower levels experienced mortality. Conclusion: Presepsin shows potential as a biomarker for identifying sepsis patients at increased risk of mortality. Its use may support early risk stratification and guide clinical decision-making in sepsis management.