Housing RCS rats under specific pathogen-free conditions mildly ameliorates retinal degeneration and alters intestine microbiota.

Retinitis pigmentosa (RP) is a genetic blinding disease with over 80 causative genes. Disease progression varies between patients with similar genetic backgrounds. We assessed the association between environment, gut microbiota, and retinal degeneration in the RP rat model Royal College of Surgeons (RCS).

Lubricating gel influence on vaginal microbiome sampling.

Gel lubrication is routinely used during gynecological examination to prevent or reduce pain, yet its impact on microbial composition during sampling remains unclear. This study aimed to investigate whether lubricating gel affects the microbial composition of vaginal samples. We included 31 pregnant women presenting during their third trimester to clinics or emergency room and collected 143 unique vaginal samples for 16S amplicon microbial analysis.

Long-term metabolic effects of non-nutritive sweeteners.

Objective: Excessive consumption of added sugars has been linked to the rise in obesity and associated metabolic abnormalities. Non-nutritive sweeteners (NNSs) offer a potential solution to reduce sugar intake, yet their metabolic safety remains debated. This study aimed to systematically assess the long-term metabolic effects of commonly used NNSs under both normal and obesogenic conditions.

Lack of gut microbiome recovery with spinal cord injury rehabilitation.

Spinal cord injury (SCI) is a devastating event that significantly changes daily function and quality of life and is linked to bowel and bladder dysfunction and frequent antibiotic treatment. We aimed to study the composition of the gut microbiome in individuals with SCI during the initial sub-acute rehabilitation process and during the chronic phase of the injury. This study included 100 fecal samples from 63 participants (Median age 40 years, 94% males): 13 cases with SCI in the sub-acute phase with 50 longitudinal samples, 18 cases with chronic SCI, and 32 age and gender-matched controls.

Mucosal transcriptomics highlight lncRNAs implicated in ulcerative colitis, Crohn's disease, and celiac disease.

Ulcerative colitis (UC), Crohn's disease (CD), and celiac disease are prevalent intestinal inflammatory disorders with nonsatisfactory therapeutic interventions. Analyzing patient data-driven cohorts can highlight disease pathways and new targets for interventions. Long noncoding RNAs (lncRNAs) are attractive candidates, since they are readily targetable by RNA therapeutics, show relative cell-specific expression, and play key cellular functions.

Gut microbial signature in lung cancer patients highlights specific taxa as predictors for durable clinical benefit.

We aimed to determine microbial signature linked with lung cancer (LC) diagnosis and to define taxa linked with durable clinical benefit (DCB) of advanced LC patients. Stool samples for microbial 16S amplicon sequencing and clinical data were collected from 75 LC patients (50 of which were treated with checkpoint inhibitors) and 31 matched healthy volunteers. We compared LC to healthy controls and patients with DCB to those without.

Outbreak of Sepsis Following Surgery: Utilizing 16S RNA Sequencing To Detect the Source of Infection.

Background Nosocomial infections are a significant health concern. Following surgery, infections are most commonly associated with the surgical site, yet there are other potential sources for infections after surgical interventions. Identification of the source of infections can be very challenging.

Gut microbiome development in early childhood is affected by day care attendance.

The human gut microbiome develops during the first years of life, followed by a relatively stable adult microbiome. Day care attendance is a drastic change that exposes children to a large group of peers in a diverse environment for prolonged periods, at this critical time of microbial development, and therefore has the potential to affect microbial composition. We characterize the effect of day care on the gut microbial development throughout a single school year in 61 children from 4 different day care facilities, and in additional 24 age-matched home care children (n = 268 samples, median age of entering the study was 12 months).

Defining the Celiac Disease Transcriptome using Clinical Pathology Specimens Reveals Biologic Pathways and Supports Diagnosis.

Celiac disease is provoked by gluten exposure, but the complete pathogenic process in the duodenum and the loss of tolerance to gluten is not well understood. We aimed to define the core celiac transcriptomic signature and pathologic pathways in pre-treatment formalin-fixed paraffin-embedded (FFPE) duodenum biopsies used for clinical diagnosis. We use mRNAseq to define pre-treatment diagnostic duodenum gene expression in 54 pediatric celiac patients and non-celiac controls, and we validate our key findings in two independent cohorts of 67 adults and pediatric participants that used fresh frozen biopsies.

De-novo protein function prediction using DNA binding and RNA binding proteins as a test case.

Of the currently identified protein sequences, 99.6% have never been observed in the laboratory as proteins and their molecular function has not been established experimentally. Predicting the function of such proteins relies mostly on annotated homologs.

Novel mechanism whereby nuclear factor kappaB mediates DNA damage repair through regulation of O(6)-methylguanine-DNA-methyltransferase.

O(6)-Methylguanine-DNA-methyltransferase (MGMT) and nuclear factor kappaB (NF-kappaB) are two key effectors associated with the development of resistance to alkylating agent-based chemotherapy. This prompted us to hypothesize that NF-kappaB might be involved in MGMT regulation. Consistent with this hypothesis, we have discovered two putative NF-kappaB binding sites within the MGMT promoter region and showed a specific and direct interaction of NF-kappaB at each of these sites.

A novel synthetic cannabinoid derivative inhibits inflammatory liver damage via negative cytokine regulation.

The therapeutic potential of cannabinoids has been described previously for several inflammatory diseases, but the molecular mechanisms underlying the anti-inflammatory properties of cannabinoids are not well understood. In this study, we investigated the mechanism of action of a novel synthetic cannabinoid, [(+)(6aS,10aS)-6,6-Dimethyl-3-(1,1-dimethylheptyl)-1-hydroxy-9-(1H-imidazol-2-ylsulfanylmethyl]-6a,7,10,10a-tetrahydro-6H-dibenzo[b,d]pyran (PRS-211,092) that has no psychotropic effects but exhibits immunomodulatory properties. Treatment with PRS-211,092 significantly decreased Concanavalin A-induced liver injury in mice that was accompanied by: 1) promotion of early gene expression of interleukin (IL)-6 and IL-10 that play a protective role in this model; 2) induction of early gene expression of the suppressors of cytokine signaling (SOCS-1 and 3), followed by 3) inhibition of several pro-inflammatory mediators, including IL-2, monocyte chemoattractant protein-1 (MCP-1), IL-1beta, interferon-gamma, and tumor necrosis factor alpha.