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Introduction: Cutibacterium acnes (C. acnes) resides in various organs such as the skin, prostate, eye, nose, stomach, and intestine, indicating the possibility of extensive crosstalk between this bacterium and the human body. C. acnes strains are classified into three subspecies based on phylogenetics and distinguishable phenotypes. Among them, C. acnes subsp. defendens strains are characterized by anti-inflammatory features, raising expectations for their potential as future microbiome therapeutics. However, the heterogeneity of C. acnes subsp. defendens and its corresponding immunological functions have not been clearly addressed. Methods: The genetic diversity of the strains was assessed using single- and multi-locus sequence typing. Their immune-modulatory functions were evaluated in vitro using 2D and 3D assays with immune and epithelial cells. The anti-inflammatory effects were further confirmed in vivo using a rosacea-like mouse model. Comparative genomic and transcriptomic analyses were conducted to uncover mechanisms underlying the immunosuppressive activity of the strains. Results: We demonstrated that the newly isolated C. acnes subsp. defendens strains, exhibiting phenotypic heterogeneity, are distinctly clustered using single- and multi-locus sequence typing methods. These strains showed strong immune-regulatory functions in immune and epithelial cell-based 2D and 3D in vitro assays. Furthermore, their anti-inflammatory role was functionally confirmed in vivo using a rosacea-like mouse model, where they alleviated skin lesions characterized by hyperplasia and dermal inflammation. Comparative transcriptomics revealed that these strains may exert their immunosuppressive effects through the enhanced expression of acnecins and transcriptional variation in envelope stress regulators (specifically the two-component systems, CesSR homologs). Additionally, we propose that these C. acnes type II strains produce anti-inflammatory metabolites or peptides smaller than 3 kDa, which are associated with elevated pyrimidine and reduced L-arginine biosynthesis. Discussion: The newly isolated C. acnes subsp. defendens strains demonstrate significant anti-inflammatory properties both in vitro and in vivo , suggesting their potential as microbiome-based therapeutics. Their unique genomic and transcriptomic profiles, including the production of small bioactive compounds and specific transcriptomic patterns, underpin their immunosuppressive capabilities. These findings provide a foundation for developing novel treatments for inflammatory skin conditions, such as rosacea. [ABSTRACT FROM AUTHOR]

Purpose Despite the recent success of Bruton's tyrosine kinase (BTK) inhibitors for the treatment of Waldenstrom macroglobulinemia (WM), their indefinite treatment duration ultimately tantamount to substantial financial and emotional burden. On the other hand, fixed duration of proteasome inhibitors (PI) have shown rapid and reasonable response in WM treatment. Despite the well-known synergism between PI and immunomodulatory drugs (IMiD), there is no trials evaluating such combination in WM. Materials and Methods Based on above, we designed this phase II study to investigate the efficacy and safety of 6 cycles of 28-day bortezomib-thalidomide-dexamethasone (VTD) regimen for treatment-naïve WM. Results A total of 15 patients were enrolled: major response rate was 64.3%, and overall response rate was 78.6%. During the median follow-up of 41 months, median progression-free survival (PFS) was 13 months and overall survival 40 months. For responders, median duration of response was 13 months and median PFS 19 months. The most common adverse event (AE) of any grade was constipation (57.1%). The most common grade = 3 AE was anemia (21.4%). Conclusion All in all, we hereby provide proof-of-concept that PI + IMiD may be an attractive backbone for fixed duration treatment. It should be noted that granting the same level of access to newer drugs globally is virtually impossible. Thus efforts to develop regimens using readily available drugs to yield similar or adequate treatment outcomes should not be disregarded. In this sense, we believe our study holds its place for its novelty and eloquently addresses achieving the daunting societal quest of health equity. [ABSTRACT FROM AUTHOR]

Background: There is a growing concern that particulate matter (PM) such as PM2.5 and PM10 has contributed to exacerbating psychological disorders, particularly depression. However, little is known about the roles of these air pollutants on depression in elderly. Therefore, this study aimed to examine the association between PM2.5 and PM10, and depression in the elderly population in South Korea. Methods: We used panel survey data, the Korean Longitudinal Study of Aging (KLoSA), administered by the Labor Institute during the study period of 2016, 2018, and 2020 covering 217 districts in South Korea (n = 7674). Annual district-specific PM2.5 and PM10 concentrations were calculated for the study period from the monthly prediction concentrations produced by a machine-learning-based ensemble model (cross-validated R2: 0.87), then linked to the people matching with year and their residential district. We constructed a generalized estimating equation (GEE) model with a logit link to identify the associations between each of the long-term PM2.5 and PM10 exposures and depression (CES-D 10) after adjusting for individual and regional factors as confounders. Results: In single-pollutant models, we found that long-term 10 μ g / m 3 increments in PM2.5 (OR 1.36, 95% CI 1.20–1.56) and PM10 (OR 1.19, 95% CI 1.10–1.29) were associated with an increased risk of depression in the elderly. Associations were consistent after adjusting for other air pollutants (NO2 and O3) in two-pollutant models. In addition, the impacts substantially differed by regions grouped by the tertile of the population density, for which the risks of particulate matters on depression were substantial in the middle- or high-population-density areas in contrast to the low-population-density areas. Conclusions: Long-term exposure to PM2.5 and PM10 was associated with a higher risk of developing depression in elderly people. The impact was modified by the population density level of the region where they reside. [ABSTRACT FROM AUTHOR]