Alterations in the composition of the gut microbiota affect absorption of cholecalciferol in severe osteoporosis.

INTRODUCTION: To evaluate the relationship between the gut microbial composition and intestinal cholecalciferol absorption in patients with severe osteoporosis (SOP). MATERIALS AND METHODS: Eighteen patients with primary osteoporosis (OP) and 18 with SOP were included. Their clinical data were collected and their circulating concentrations of cholecalciferol and 25(OH)D3 were measured. Fecal samples were collected and their microbial contents were analyzed using 16S rDNA sequencing. RESULTS: The age, sex, body mass index, and body mass of the participants did not differ between the groups. The prevalence of gastrointestinal symptoms in the participants with SOP was significantly higher than that in the participants with OP. There were significant differences in the 25(OH)D3 and cholecalciferol concentrations between participants with SOP or OP and there was a significant positive correlation between the concentrations of these substance. The diversity of the gut microbiota in participants with SOP was significantly higher than that in participants with OP. Firmicutes was more abundant in the SOP group and the ratio of Firmicutes/Bacteroidetes in participants with SOP was higher. Conversely, Bifidobacterium was significantly less abundant, as were the order and family it belongs to. At the species level, Bifidobacterium was the most significant difference between the two groups. CONCLUSION: Differences in the intestinal microecology, especially Bifidobacterium, are associated with differences in the absorption of cholecalciferol and in the circulating 25(OH)D3 concentration, which may influence the progression of OP to SOP.

Recent Advances in the Molecular Mechanisms Underlying Pyroptosis in Sepsis.

Sepsis is recognized as a life-threatening organ dysfunctional disease that is caused by dysregulated host responses to infection. Up to now, sepsis still remains a dominant cause of multiple organ dysfunction syndrome (MODS) and death among severe condition patients. Pyroptosis, originally named after the Greek words "pyro" and "ptosis" in 2001, has been defined as a specific programmed cell death characterized by release of inflammatory cytokines. During sepsis, pyroptosis is required for defense against bacterial infection because appropriate pyroptosis can minimize tissue damage. Even so, pyroptosis when overactivated can result in septic shock, MODS, or increased risk of secondary infection. Proteolytic cleavage of gasdermin D (GSDMD) by caspase-1, caspase-4, caspase-5, and caspase-11 is an essential step for the execution of pyroptosis in activated innate immune cells and endothelial cells stimulated by cytosolic lipopolysaccharide (LPS). Cleaved GSDMD also triggers NACHT, LRR, and PYD domain-containing protein (NLRP) 3-mediated activation of caspase-1 via an intrinsic pathway, while the precise mechanism underlying GSDMD-induced NLRP 3 activation remains unclear. Hence, this study provides an overview of the recent advances in the molecular mechanisms underlying pyroptosis in sepsis.

The Parenteral Vitamin C Improves Sepsis and Sepsis-Induced Multiple Organ Dysfunction Syndrome via Preventing Cellular Immunosuppression.

Cellular immunosuppression appears to be involved in sepsis and sepsis-induced multiple organ dysfunction syndrome (MODS). Recent evidence showed that parenteral vitamin C (Vit C) had the ability to attenuate sepsis and sepsis-induced MODS. Herein, we investigated the impact of parenteral Vit C on cellular immunosuppression and the therapeutic value in sepsis. Using cecal ligation and puncture (CLP), sepsis was induced in WT and Gulo-/- mice followed with 200 mg/Kg parenteral Vit C administration. The immunologic functions of CD4+CD25+ regulatory T cells (Tregs) and CD4+CD25- T cells, as well as the organ functions, were determined. Administration of parenteral Vit C per se markedly improved the outcome of sepsis and sepsis-induced MODS of WT and Gulo-/- mice. The negative immunoregulation of Tregs was inhibited, mainly including inhibiting the expression of forkhead helix transcription factor- (Foxp-) 3, cytotoxic T lymphocyte associated antigen- (CTLA-) 4, membrane associated transforming growth factor-ß (TGF-ßm+), and the secretion of inhibitory cytokines [including TGF-ß and interleukin- (IL-) 10], as well as CD4+ T cells-mediated cellular immunosuppression which was improved by parenteral Vit C in WT and Gulo-/- septic mice. These results suggested that parenteral Vit C has the ability to improve the outcome of sepsis and sepsis-induced MODS and is associated with improvement in cellular immunosuppression.

Blue rubber bleb nevus syndrome complicated with disseminated intravascular coagulation and intestinal obstruction: A case report.

BACKGROUND: Blue rubber bleb nevus syndrome is a rare vascular malformation syndrome with unclear etiopathogenesis and noncurative treatments. It is characterized by multiple vascular malformations of the skin, gastrointestinal tract, and other visceral organs. The most common symptoms are intermittent gastrointestinal bleeding and secondary iron deficiency anemia, thus requiring repeated blood transfusions and hospitalizations. It is easily missed and misdiagnosed, and there is no specific treatment. CASE SUMMARY: We report a case of blue rubber bleb nevus syndrome combined with disseminated intravascular coagulation and efficacy of treatment with argon plasma coagulation under enteroscopy and sirolimus. A 56-year-old female patient was admitted to the hospital with 3-year history of fatigue and dizziness that had aggravated over the past 10 d with melena. The patient had a history of repeated melena and multiple venous hemangiomas from childhood. After treatment with argon plasma coagulation combined with sirolimus for nearly 8 wk, the patient's serum hemoglobin increased to 100 g/L. At the 12-mo follow-up, the patient was well with stable hemoglobin (102 g/L) and no recurrent intestinal bleeding. CONCLUSION: Argon plasma coagulation and sirolimus may be an efficacious and safe treatment for blue rubber bleb nevus syndrome, which currently has no recommended treatments.