BACKGROUND: Frailty significantly affects morbidity and mortality rates in the older population (age >65 years). Age-related degenerative diseases are influenced by the intestinal microbiota. However, limited research exists on alterations in the intestinal microbiota in frail older individuals, and the effectiveness of prebiotic intervention for treating frailty remains uncertain. OBJECTIVE: We sought to examine the biological characteristics of the intestinal microbiome in frail older individuals and assess changes in both frailty status and gut microbiota following intervention with a prebiotic blend consisting of inulin and oligofructose. METHODS: The study consisted of 3 components: an observational analysis with a sample size of 1,693, a cross-sectional analysis ( n = 300), and a multicenter double-blind, randomized, placebo-controlled trial ( n = 200). Body composition, commonly used scales, biochemical markers, intestinal microbiota, and metabolites were examined in 3 groups of older individuals (nonfrail, prefrail, and frail). Subsequently, changes in these indicators were reevaluated after a 3-month intervention using the prebiotic mixture for the prefrail and frail groups. RESULTS: The intervention utilizing a combination of prebiotics significantly improved frailty and renal function among the older population, leading to notable increases in protein levels, body fat percentage, walking speed, and grip strength. Additionally, it stimulated an elevation in gut probiotic count and induced alterations in microbial metabolite expression levels as well as corresponding metabolic pathways. CONCLUSIONS: The findings suggest a potential link between changes in the gut microbiota and frailty in older adults. Prebiotics have the potential to modify the gut microbiota and metabolome, resulting in improved frailty status and prevention of its occurrence. TRIAL REGISTRATION: ClinicalTrials.gov NCT03995342.

Pancreatic adenocarcinoma (PAAD) is a highly malignant tumor of the digestive system with increasing morbidity and mortality. The lack of sensitive and reliable biomarkers is one of the main reasons for the poor prognosis. Volume-regulated anion channels (VRAC), which are ubiquitously expressed in the vertebrate cell membrane, are composed of leucine-rich repeat-containing 8A (LRRC8A) and four other homologous family members (LRRC8B–E). VRAC heterogeneous complex is implicated in each of the six “hallmarks of cancer” and represents a novel therapeutic target for cancer. In this study, LRRC8A was speculated to be a promising prognostic biomarker and therapeutic target for PAAD based on a series of bioinformatics analyses. Additional cell experiments and immunohistochemical assays demonstrated that LRRC8A can affect the prognosis of PAAD and is correlated to cell proliferation, cell migration, drug resistance, and immune infiltration. Functional analysis indicated that LRRC8A influences the progression and prognosis of patients with PAAD by the regulation of CD8⁺ T cells immune infiltration. Taken together, these results can help in the design of new therapeutic drugs for patients with PAAD.

Cardiovascular diseases (CVDs) are the leading cause of morbidity and mortality worldwide. Although there are established mechanisms and preventions for CVDs, they are not totally elucidative and effective. Emerging evidence suggests that the dysregulation of ion channels in the cell membranes underpins the dysfunction of the cardiovascular system. To date, a variety of cation channels have been widely recognized as important targets for the treatment of CVDs. As a critical component of the anion channels, the volume-regulated anion channel (VRAC) is involved in a series of cell functions by the volume regulation and maintenance of membrane homeostasis. It has been confirmed to play crucial roles in cell action potential generation, cell proliferation, differentiation and apoptosis, and the VRAC appears to be a major participant in metabolic processes during CVDs. This review summarizes the current evidence and progress concerning the VRAC, to determine the future directions and challenges for CVDs for both preventive and therapeutic purposes.

Neuroendocrine prostate cancer (NEPC) is a lethal subtype of prostate cancer (PCa) that emerges under androgen deprivation and is associated with therapeutic resistance. The contribution of volume-regulated anion channels (VRACs) to this process remains poorly understood. This study identified leucine-rich repeat-containing 8 subunit D (LRRC8D), a VRAC subunit, as the only family member consistently downregulated in NEPC and associated with neuroendocrine (NE)-like features. LRRC8D downregulation was accompanied by suppression of swelling-activated VRAC currents, increased synaptophysin (SYP) expression, decreased cisplatin sensitivity, and neurosecretory remodeling. Conversely, LRRC8D overexpression enhanced cisplatin-induced apoptosis, reduced colony formation, and suppressed tumor growth in xenograft models, including under cisplatin treatment. Consistent alterations in LRRC8D and SYP expression were also observed in enzalutamide-resistant patient-derived organoids. Mechanistically, RE1-silencing transcription factor (REST) promoted LRRC8D transcription. Functional analyses further demonstrated that CAV-1 acted upstream of LRRC8D, and LRRC8D negatively regulated STAT3 activation. Together, these findings indicate that LRRC8D influences PCa phenotype and platinum responsiveness, and implicate a regulatory axis involving LRRC8D and CAV-1/STAT3 signaling in NE-associated features of advanced PCa. Functional analyses further showed that CAV-1 acted upstream of LRRC8D, and LRRC8D negatively regulated STAT3 activation. Together, these findings indicate that LRRC8D influences PCa phenotype and platinum responsiveness and implicate a regulatory axis involving LRRC8D and CAV-1/STAT3 signaling in NE-associated features of advanced PCa.

The clinical features of bacteria endocarditis became atypical when consolidated with other conditions such as tuberculosis (TB). Especially, the symptoms of bacteria endocarditis (BE) which were hidden behind the TB fever often lead to misdiagnosis and missed diagnosis. A 56-year-old male with thoracic vertebra bone TB history presented with low-grade fever, shortness of breath and cardiac souffle. After conventional antibiotic therapy and strengthen anti-tuberculosis treatment condition did not be improved. Further inspection, there were bacteria endocarditis with the vegetation across the mitral valve. But the other valves were not involved. He was treated with intravenous penicillin for 4 weeks in all including during surgery, and following with oral antibiotic for another 2 weeks. The patient improved clinically eventually. It is the first reported case of isolated thoracic vertebra tuberculosis with valve endocarditis caused by streptococcus viridans and was successfully managed by combination therapy of internal medicine and surgery. It was suggested in tuberculosis patients, the possibility of bacterial endocarditis should be considered when came into fever and unexplained cardiac soufflé (in tuberculosis patients).