Crescent calculator: A webtool enabling objective decision-making for assessment of IgA nephropathy immune activity throughout the disease course.

IgA nephropathy (IgAN) is an immune-mediated glomerulonephritis, posing a challenge for the long-term management. It is crucial to monitor the disease's activity over the disease course. Crescent lesions have been known as an active lesion associated with immune activity. We aimed to develop the Crescent Calculator to aid clinicians in making timely and well-informed decisions throughout the long-term disease course, such as renal biopsies and immunosuppressive therapy. 1,761 patients with biopsy-proven IgAN were recruited from four medical centers in Zhejiang Province, China. 16.9% presented crescent lesions. UPCR, URBC, eGFR and C4 were independently associated with the crescent lesions. By incorporating these variables, the Crescent Calculator was constructed to estimate the likelihood of crescent lesions. The predictor achieved AUC values of over 0.82 in two independent testing datasets. In addition, to fulfill varied clinical needs, multiple classification modes were established. The Crescent Calculator was developed to estimate the risk of crescent lesions for patients with IgAN, assisting clinicians in making timely, objective, and well-informed decisions regarding the need for renal biopsies and more appropriate use of immunosuppressive therapy in patients with IgAN.

The gut microbe Bacteroides fragilis ameliorates renal fibrosis in mice.

Renal fibrosis is an inevitable outcome of various manifestations of progressive chronic kidney diseases (CKD). The need for efficacious treatment regimen against renal fibrosis can therefore not be overemphasized. Here we show a novel protective role of Bacteroides fragilis (B. fragilis) in renal fibrosis in mice. We demonstrate decreased abundance of B. fragilis in the feces of CKD patients and unilateral ureteral obstruction (UUO) mice. Oral administration of live B. fragilis attenuates renal fibrosis in UUO and adenine mice models. Increased lipopolysaccharide (LPS) levels are decreased after B. fragilis administration. Results of metabolomics and proteomics studies show decreased level of 1,5-anhydroglucitol (1,5-AG), a substrate of SGLT2, which increases after B. fragilis administration via enhancement of renal SGLT2 expression. 1,5-AG is an agonist of TGR5 that attenuates renal fibrosis by inhibiting oxidative stress and inflammation. Madecassoside, a natural product found via in vitro screening promotes B. fragilis growth and remarkably ameliorates renal fibrosis. Our findings reveal the ameliorative role of B. fragilis in renal fibrosis via decreasing LPS and increasing 1,5-AG levels.

Blocking of stromal interaction molecule 1 expression influence cell proliferation and promote cell apoptosis in vitro and inhibit tumor growth in vivo in head and neck squamous cell carcinoma.

Calcium signal plays an important role in a variety of cancer cell metabolism, but knowledge on its role in head and neck squamous cell carcinoma (HNSCC) is limited. Store-operated calcium entry (SOCE) is the principal Ca2+ entry mechanism that maintains calcium concentration and produces calcium signal in non-excitable cells. SOCE is triggered by stromal interaction molecule 1 (STIM1), which is located in endoplasmic reticulum (ER) as Ca2+ sensor. Although, many studies demonstrated that STIM1 and SOCE play important functions in the regulation of many cancer progressions, their clinical relevance in HNSCC remains unclear. In this study, STIM1 expression levels notably increased in 89% HNSCC tissues compared with those in adjacent normal tissues. Meanwhile, this overexpression was close associated with tumor size but not with neck lymph node metastasis. Thus, this study mainly focuses on STIM1 function in HNSCC tumor growth. Three HNSCC cell lines, namely, TSCCA (oral cancer cell line) and Hep2 (laryngeal cell line) with high STIM1 expression levels and Tb3.1 (oral cancer cell line) with STIM1 expression level lower than previous two cell lines, were selected for in vitro study. Downregulated STIM1 expression levels in TSCCA and Hep2 arrested cells in G0/G1 stages, promoted cell apoptosis, and inhibited cell proliferation. By contrast, upregulated STIM1 expression in Tb3.1 inhibited cell apoptosis and promoted cell proliferation. Induced by thapsigargin (TG), ER stress was amplified when STIM1 expression was downregulated but was attenuated as STIM1 expression was upregulated. Furthermore, TSCCA cell xenograft models confirmed that STIM1 could promote HNSCC tumor growth in vivo. The present study provides new insight into HNSCC molecular mechanism and potential therapeutic target through targeting SOCE-dependent process. However, whether STIM1 participates in HNSCC metastasis requires further study.