Progress In Microbes & Molecular Biology

Therapeutic and Pharmacological Role of Natural Products in Neurological Diseases: Targeting Autophagy Pathways

2025-04-12T07:10:06+08:00

The mounting interest in botanical-derived natural products for neuroprotection gains significant attention for their prevalence, diverse array of bioactive constituents, and roles in traditional and modern medicine. While numerous address neuroprotective mechanisms of botanical products, few focus specifically on their autophagy effects. This review conducted a systematic analysis following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Relevant studies were extracted from the Google Scholar, Scopus, and PubMed databases up to February 28, 2024. Inclusion criteria targeted original English studies examining neuroprotective effects of botanicals associated with autophagy pathways in human clinical studies, in vitro models, and in vivo models. A total of 104 studies were included, comprising 32 cell-based studies, 52 animal-based studies, and 20 studies that employed both in vitro and in vivo models. These studies were categorized by botanical families and species, focusing on their neuroprotective activities and specific neurological diseases, including Alzheimer’s disease, Parkinson’s disease, and stroke. Results show that families such as Fabaceae and Apiaceae were frequently investigated for their autophagy-modulating neuroprotective potential. Notable botanical species, including Panax ginseng, Glycyrrhiza uralensis, Polygala tenuifolia, Angelica sinensis, and Paeonia lactiflora, have demonstrated promising neuroprotective effects by regulating autophagy processes, including initiation, elongation, maturation, and selective degradation, across neurological disease models. The review emphasizes the necessity for further investigation into the specific mechanisms by which these botanicals modulate autophagy and their therapeutic applications in neurological diseases. This comprehensive analysis establishes a foundation for future studies developing effective botanical-based interventions targeting autophagy pathways in neurodegenerative diseases.

Association Between Salivary C-Reactive Protein Levels and Covariates in an Older Adult Population in Malaysia — A Cross-Sectional Study of The MyAgeWell Cohort

2024-09-10T16:48:42+08:00

Malaysia's aging population faces heightened risks of cardiovascular diseases, cancers, metabolic disorders, and physical and cognitive decline. Inflammatory biomarkers, such as C-reactive protein (CRP), play a key role in age-related ailments. For instance, elevated CRP levels are linked to an increased risk of cardiovascular diseases and cognitive decline. It is of particular interest to investigate CRP levels and their correlation with various factors among older adults to develop potential predictive markers and interventions for age-related diseases. In recent years, salivary samples have become a viable non-invasive alternative approach to studying CRP levels. Hence, this study aims to examine salivary CRP levels and explore the influences of age, ethnicity, gender, body mass index (BMI) and economic status on salivary CRP levels among older adults. The study was registered at ClinicalTrials.gov (NCT06376656) and ethical approval was obtained from the Sunway University Research Ethics Committee (SUREC 2020/039). A total of 382 saliva samples were collected from the older adults (≥ 60 years) through the MyAgeWell cohort for analysis. Various covariates including age, gender, ethnicity, BMI, and economic status were recorded. Salivary CRP levels were measured using ELISA. We observed a median CRP concentration of 0.39 ng/mL (IQR = 0 – 1.36 ng/mL). Correlation analysis shows salivary CRP levels were associated with gender, ethnicity, and BMI (p < 0.05), but not age and economic status. These findings suggest diverse influences on inflammation among Malaysian older adults. In conclusion, this study advances the understanding of salivary CRP levels in healthy older adults, highlighting the complex nature of inflammation in this population and the importance of addressing modifiable risk factors to reduce health disparities.

Pilot Trial of Probiotics in Major Depressive Disorder: A Randomized, Double-Blind, Placebo-Controlled Approach

2025-04-03T17:25:48+08:00

Depression affects approximately 280 million people globally and is projected to become the leading cause of disease burden by 2030. Emerging evidence suggests that probiotics may play a role in managing depression by modulating the gut-brain axis. Therefore, as a pioneering research initiative, we conducted a pilot study in a Malaysian setting, presenting it as a preliminary report on the potential effects of probiotics on depressive symptoms in patients with mild major depressive disorder (MDD) and the associated stool-derived gut microbiome changes. The primary aim was to provide initial insights into the potential effects of probiotics as a stand-alone treatment for mild MDD while also assessing the feasibility of the study. Malaysian adults aged 18–65 with clinically diagnosed mild MDD were randomized in a 3:1 ratio to receive either multi-strain probiotics (Lactobacillus helveticus R0052, Lactobacillus rhamnosus R0011, Bifidobacterium longum R0175, and Saccharomyces cerevisiae boulardii) or a starch-only placebo for six weeks. The primary outcome was overall depressive symptomatology assessed using the Beck Depression Inventory, with additional clinical measures including the Patient Global Impression and Clinical Global Impression scales. Gut microbiome profiling was conducted using 16S rRNA gene sequencing of stool samples. Of 81 initial respondents, 15 met the inclusion criteria and were randomised (probiotic: n=12, placebo: n=3). Key exclusions included current or recent (past month) use of antidepressants or psychiatric treatment and the presence of psychiatric comorbidities. Three probiotic participants dropped out, resulting in a per-protocol analysis of probiotic (n=9) and placebo (n=3) groups for clinical assessments, and probiotic (n=7) and placebo (n=3) for microbiome analysis. Probiotic supplementation led to statistically significant improvements in depressive symptoms, severity, and overall improvement (p<0.05), with no significant changes observed in the placebo group. Effect sizes post-intervention (d_post=0.3) and pre-post (d_pre-post=1.282) suggest that probiotics outperformed placebo, with a modest effect size comparable to clinical antidepressant trials. Gut microbiome analysis showed no significant differences in diversity measures but revealed distinct shifts in microbial composition, with increases in beneficial taxa associated with greater clinical improvement. Despite recruitment challenges, the intervention was well-tolerated, and compliance was high. While findings are promising, the small sample size limits generalisability. Larger studies are needed to confirm these results and explore the long-term effects of probiotics in depression management.

Mechanistic Insights into the Inhibition of Colorectal Cancer by BuShenFang through Adenomatous Polyposis Coli Expression and Wnt/β-catenin Pathway Regulation

2025-01-15T19:04:58+08:00

Colorectal cancer (CRC) remains one of the leading causes of cancer-related mortality worldwide. Despite advances in chemotherapy and radiotherapy, significant side effects persist, prompting the exploration of alternative therapies such as traditional Chinese medicine (TCM). BuShenFang (BSF), a TCM formulation, is believed to exhibit anti-CRC effects, although its exact mechanism is unclear. This study aims to investigate the effects of BSF on CRC cells through the modulation of the Wnt/β-catenin pathway. The study utilized HCT116 and SW620 CRC cell lines, employing in vitro experiments including cell viability assays, colony formation, flow cytometry, and Western blot to examine the influence of BSF on cellular proliferation, apoptosis, migration, and the Wnt/β-catenin signaling pathway. Results demonstrated that BSF significantly inhibited the proliferation of CRC cells in a dose-dependent manner. The apoptotic rate was markedly increased in the 20% BSF group, while colony formation, migration, and invasion capabilities of CRC cells were notably suppressed. Furthermore, Western blot results revealed that BSF enhanced adenomatous polyposis coli (APC) expression and inhibited β-catenin, c-Myc, and Cyclin D1, key proteins in the Wnt/β-catenin pathway. In conclusion, BSF exerts anti-CRC effects by modulating the Wnt/β-catenin pathway, suggesting its potential as a complementary therapeutic agent in CRC treatment. Future studies should focus on in vivo models to validate these findings.

Probiotics in Depression Management: Efficacy, Mechanisms and Future Directions

2025-01-15T17:29:42+08:00

Depression affects approximately 280 million people worldwide, representing a significant public health burden. It is characterized by persistent sadness, anhedonia, fatigue, sleep disturbances, cognitive dysfunction, and in severe cases, suicidal ideation. The pathophysiology is often attributed to neurotransmitter imbalances, hypothalamic-pituitary-adrenal (HPA) axis dysfunction, and inflammation. Recently, the gut-brain axis has garnered attention for its role in mood regulation, suggesting that probiotic supplementation may influence depressive symptoms through gut microbiome modulation. Therefore, this review examines recent findings and research gaps regarding the efficacy of probiotics in managing clinically diagnosed depression. Emerging research demonstrates that daily probiotic supplementation from 3×10⁹ CFU to 9×10¹¹ CFU for four to eight weeks in combination with antidepressants is effective in improving depressive symptoms. Effective formulations commonly included Bifidobacteria, Lactobacilli, Lactococcus lactis, and Streptococcus thermophilus. Nevertheless, significant gaps remain, particularly concerning the mechanistic pathways, comparative effectiveness, and impact across different demographics of the probiotics. Furthermore, the long-term effects of probiotic use with antidepressants, their role in reducing antidepressant side effects, and combined effects with psychotherapy are largely understudied. Addressing these gaps through standardized methodologies will enhance evaluations of probiotic strains to optimize microbiome-based treatment regimens, and ultimately improve mental health outcomes in depression management.

Graphical abstract. Summary of research gaps and future directions to determine the efficacy of probiotics in diagnosed depression.

DNA Methylation: Its Role and Interaction with Epigenetic Modifications in Cancer

2025-01-15T16:16:20+08:00

DNA methylation is an epigenetic mark involving the addition of a methyl group to DNA, particularly at cytosine residues. This methylation plays an important role in regulating gene expression through direct gene repression or through the control of other epigenetic modifications such as histone modification or chromatin remodeling. DNA methylation is catalyzed by de novo and maintenance DNMT methyltransferase type enzymes and requires the transfer of a methyl group to cytosine to transform it into 5-methyl-cytosine. Currently, several investigations have highlighted the involvement of aberrant DNA methylation with certain tumors. Indeed, the methylation of antioncogenes and/or the demethylation of oncogenes are the major alterations that are strongly linked to human cancers. DNMTs play a central role in the epigenetic regulation of the human genome, both in normal and pathological processes. Recent discoveries on the differentiated roles of DNMTs in DNA methylation, and their implication in various cancers, open the way to new therapeutic approaches targeting these enzymes to treat epigenetic diseases. It is essential to continue exploring the roles of DNMTs to better understand their implication in tumorigenesis mechanisms and to develop more effective treatment strategies.