Positive modulation of a new reconstructed human gut microbiota by Maitake extract helpfully boosts the intestinal environment <i>in vitro</i>

by Alessandra De Giani, Federica Perillo, Alberto Baeri, Margherita Finazzi, Federica Facciotti, Patrizia Di Gennaro

The human gut is a complex environment where the microbiota and its metabolites play a crucial role in the maintenance of a healthy state. The aim of the present work is the reconstruction of a new in vitro minimal human gut microbiota resembling the microbe-microbe networking comprising the principal phyla (Bacillota, Bacteroidota, Pseudomonadota, and Actinomycetota), to comprehend the intestinal ecosystem complexity. In the reductionist model, we mimicked the administration of Maitake extract as prebiotic and a probiotic formulation (three strains belonging to Lactobacillus and Bifidobacterium genera), evaluating the modulation of strain levels, the release of beneficial metabolites, and their health-promoting effects on human cell lines of the intestinal environment. The administration of Maitake and the selected probiotic strains generated a positive modulation of the in vitro bacterial community by qPCR analyses, evidencing the prominence of beneficial strains (Lactiplantibacillus plantarum and Bifidobacterium animalis subsp. lactis) after 48 hours. The bacterial community growths were associated with the production of metabolites over time through GC-MSD analyses such as lactate, butyrate, and propionate. Their effects on the host were evaluated on cell lines of the intestinal epithelium and the immune system, evidencing positive antioxidant (upregulation of SOD1 and NQO1 genes in HT-29 cell line) and anti-inflammatory effects (production of IL-10 from all the PBMCs). Therefore, the results highlighted a positive modulation induced by the synergic activities of probiotics and Maitake, inducing a tolerogenic microenvironment.

Identification of differentially expressed mRNA/lncRNA modules in acutely regorafenib-treated sorafenib-resistant Huh7 hepatocellular carcinoma cells

by Mina Baek, Minjae Kim, Hae In Choi, Bert Binas, Junho Cha, Kyoung Hwa Jung, Sungkyoung Choi, Young Gyu Chai

The multikinase inhibitor sorafenib is the standard first-line treatment for advanced hepatocellular carcinoma (HCC), but many patients become sorafenib-resistant (SR). This study investigated the efficacy of another kinase inhibitor, regorafenib (Rego), as a second-line treatment. We produced SR HCC cells, wherein the PI3K-Akt, TNF, cAMP, and TGF-beta signaling pathways were affected. Acute Rego treatment of these cells reversed the expression of genes involved in TGF-beta signaling but further increased the expression of genes involved in PI3K-Akt signaling. Additionally, Rego reversed the expression of genes involved in nucleosome assembly and epigenetic gene expression. Weighted gene co-expression network analysis (WGCNA) revealed four differentially expressed long non-coding RNA (DElncRNA) modules that were associated with the effectiveness of Rego on SR cells. Eleven putative DElncRNAs with distinct expression patterns were identified. We associated each module with DEmRNAs of the same pattern, thus obtaining DElncRNA/DEmRNA co-expression modules. We discuss the potential significance of each module. These findings provide insights and resources for further investigation into the potential mechanisms underlying the response of SR HCC cells to Rego.

Potential efficacy of caffeine ingestion on balance and mobility in patients with multiple sclerosis: Preliminary evidence from a single-arm pilot clinical trial

by Afsoon Dadvar, Melika Jameie, Mehdi Azizmohammad Looha, Mohammadamin Parsaei, Meysam Zeynali Bujani, Mobina Amanollahi, Mahsa Babaei, Alireza Khosravi, Hamed Amirifard

Objectives

Caffeine’s potential benefits on multiple sclerosis (MS), as well as on the ambulatory performance of non-MS populations, prompted us to evaluate its potential effects on balance, mobility, and health-related quality of life (HR-QoL) of persons with MS (PwMS).

Methods

This single-arm pilot clinical trial consisted of a 2-week placebo run-in and a 12-week caffeine treatment (200 mg/day) stage. The changes in outcome measures during the study period (weeks 0, 2, 4, 8, and 12) were evaluated using the Generalized Estimation Equation (GEE). The outcome measures were the 12-item Multiple Sclerosis Walking Scale (MSWS-12) for self-reported ambulatory disability, Berg Balance Scale (BBS) for static and dynamic balance, Timed Up and Go (TUG) for dynamic balance and functional mobility, Multiple Sclerosis Impact Scale (MSIS-29) for patient’s perspective on MS-related QoL (MS-QoL), and Patients’ Global Impression of Change (PGIC) for subjective assessment of treatment efficacy. GEE was also used to evaluate age and sex effect on the outcome measures over time. (Iranian Registry of Clinical Trials, IRCT2017012332142N1).

Results

Thirty PwMS were included (age: 38.89 ± 9.85, female: 76.7%). Daily caffeine consumption significantly improved the objective measures of balance and functional mobility (BBS; P-value Conclusions

Caffeine may enhance balance, functional mobility, and QoL in PwMS. Being male was associated with a sharper increase in self-reported ambulatory disability over time. The effects of aging on balance get more pronounced over time.

Trial registration

This study was registered with the Iranian Registry of Clinical Trials (Registration number: IRCT2017012332142N1), a Primary Registry in the WHO Registry Network.

Detection of CTLA-4 level and humeral immune response after the second dose of COVID-19 vaccine in certain Iraqi provinces participants

by Laith A. I. K. Al-Kaif, Hussain Al-Ameri, Wael Rasheed Obaead Alfatlawi, Ammar Eesa Mahdi, Younis A. K. Al-Khafaji, Mohammad Abd-Kadhum Al-Saadi, Alaa H. Al-Charrakh, Raheem T. Al-Mammori, Mohammed Ahmed Akkaif

Background

Evaluating immune responses following COVID-19 vaccination is paramount to understanding vaccine effectiveness and optimizing public health interventions. This study seeks to elucidate individuals’ immune status after administering a second dose of diverse COVID-19 vaccines. By analyzing immune responses through serological markers, we aim to contribute valuable insights into the uniformity of vaccine performance.

Methods

A total of 80 participants were enrolled in this study, with demographic and COVID-19 infection-related data collected for categorization. Serum samples were acquired within a specified timeframe, and SARS-CoV-2 IgM/IgG rapid tests were conducted. Moreover, CTLA-4 levels were measured through ELISA assays, allowing us to assess the immune responses comprehensively. The participants were divided into eight groups based on various factors, facilitating a multifaceted analysis.

Results

The outcomes of our investigation demonstrated consistent immune responses across the diverse types of COVID-19 vaccines administered in Iraq. Statistical analysis revealed no significant distinctions among the vaccine categories. In contrast, significant differences were observed in CTLA-4 among the control group (non-infected/non-vaccinated, infected/non-vaccinated) and infected/Pfizer, non-infected/Pfizer, and infected/Sinopharm, non-infected/sinopharm (P = 0.001, Conclusions

In conclusion, our study’s results underscore the lack of discriminatory variations between different COVID-19 vaccine types utilized in Iraq. The uniform immune responses observed signify the equitable efficacy and performance of these vaccines. Despite minor quantitative discrepancies, these variations do not hold statistical significance, reaffirming the notion that the various vaccines serve a similar purpose in conferring protection against COVID-19.

Altered serum TNF-α and MCP-4 levels are associated with the pathophysiology of major depressive disorder: A case-control study results

by Jannatul Nayem, Rapty Sarker, A. S. M. Roknuzzaman, M. M. A. Shalahuddin Qusar, Sheikh Zahir Raihan, Md. Rabiul Islam, Zobaer Al Mahmud

Background

Major Depressive Disorder (MDD) is a debilitating mental health condition with complex etiology, and recent research has focused on pro-inflammatory cytokines and chemokines as potential contributors to its pathogenesis. However, studies investigating the roles of TNF-α and MCP-4 in MDD within the Bangladeshi population are scarce. This study aimed to assess the association between serum TNF-α and MCP-4 levels and the severity of MDD, exploring their potential as risk indicators for MDD development.

Methods

This case-control study enrolled 58 MDD patients from Bangabandhu Sheikh Mujib Medical University (BSMMU) Hospital, Dhaka, Bangladesh, alongside 30 age, sex, and BMI-matched healthy controls. MDD diagnosis followed DSM-5 criteria and disease severity using the 17-item Hamilton Depression Rating Scale (Ham-D). We measured serum TNF-α and MCP-4 levels using ELISA assays according to the supplied protocols.

Results

The study revealed significantly elevated serum TNF-α levels in MDD patients (47±6.6 pg/ml, mean±SEM) compared to controls (28.06±1.07 pg/ml). These increased TNF-α levels positively correlated with Ham-D scores (Pearson’s r = 0.300, p = 0.038), suggesting a potential association between peripheral TNF-α levels and MDD pathology. Additionally, MDD patients exhibited significantly higher serum MCP-4 levels (70.49±6.45 pg/ml) than controls (40.21±4.08 pg/ml). However, serum MCP-4 levels showed a significant negative correlation (r = -0.270, P = 0.048) with Ham-D scores in MDD patients, indicating a more complex role for MCP-4 in MDD pathogenesis.

Conclusion

This study highlights that Bangladeshi MDD patients exhibit heightened inflammatory and immune responses compared to controls, supporting the cytokine hypothesis in MDD pathogenesis. Serum TNF-α, but not MCP-4, shows promise as a potential biomarker for assessing the risk of MDD development, which could aid in early detection. Future investigations involving larger populations and longitudinal studies are essential to confirm the utility of these cytokines as biomarkers for MDD.