Apoptosis releases hydrogen sulfide to inhibit Th17 cell differentiation.

Over 50 billion cells undergo apoptosis each day in an adult human to maintain immune homeostasis. Hydrogen sulfide (H2S) is also required to safeguard the function of immune response. However, it is unknown whether apoptosis regulates H2S production. Here, we show that apoptosis-deficient MRL/lpr (B6.MRL-Faslpr/J) and Bim-/- (B6.129S1-Bcl2l11tm1.1Ast/J) mice exhibit significantly reduced H2S levels along with aberrant differentiation of Th17 cells, which can be rescued by the additional H2S. Moreover, apoptotic cells and vesicles (apoVs) express key H2S-generating enzymes and generate a significant amount of H2S, indicating that apoptotic metabolism is an important source of H2S. Mechanistically, H2S sulfhydrates selenoprotein F (Sep15) to promote signal transducer and activator of transcription 1 (STAT1) phosphorylation and suppress STAT3 phosphorylation, leading to the inhibition of Th17 cell differentiation. Taken together, this study reveals a previously unknown role of apoptosis in maintaining H2S homeostasis and the unique role of H2S in regulating Th17 cell differentiation via sulfhydration of Sep15C38.

Controlled and Sequential Delivery of Stromal Derived Factor-1 α (SDF-1α) and Magnesium Ions from Bifunctional Hydrogel for Bone Regeneration.

Bone healing is a complex process that requires the participation of cells and bioactive factors. Stromal derived factor-1 α (SDF-1α) and magnesium ions (Mg2+) both are significant bioactive factors for cell recruitment and osteogenesis during bone regeneration. Thus, a bifunctional hydrogel containing a sequential delivery system is fabricated to improve osteogenesis. During sequential delivery of the hydrogel, SDF-1α is predominantly released at the early stage of bone mesenchymal stem cells (BMSCs) recruitment, while Mg2+ are constantly delivered at a later stage to improve osteogenic differentiation of recruited cells. In addition, due to the early release of SDF-1α, the hydrogel showed strong BMSCs recruitment and proliferation activity. Mg2+ can not only induce up-regulation of osteogenic gene expression in vitro, but also promote bone tissue and angiogenesis in vivo. Taken together, the injection of xanthan gum-polydopamine crosslinked hydrogel co-loading SDF-1α and Mg2+ (XPMS hydrogel) provides a novel strategy to repair bone defects.

Recovery pattern analysis of swallowing function in patients undergoing total glossectomy and hemiglossectomy.

OBJECTIVES: To investigate the recovery process of swallowing function and ascertain swallowing pattern in patients undergoing total glossectomy (TG). MATERIALS AND METHODS: A cohort study was conducted in consecutive patients with tongue squamous cell carcinoma who received TG/hemiglossectomy (HG) from May 2017 to December 2019. Exposure factors included tongue resection range (HG and TG) and postoperative radiotherapy (PRT and non-PRT). The swallowing functions were evaluated by M.D. Anderson dysphagia inventory (MDADI), water swallow test (WST), and tongue pressure (TP) at pretreatment, 1, 4, 7, 12, 18 and 24 months postoperatively. Videofluoroscopy swallowing study (VFSS) was applied to analyze swallowing pattern of TG patients. RESULTS: A total of 67 patients were enrolled, of which 17 underwent TG and 50 underwent HG. Both MDADI and TP of the TG and PRT group were lower than those of the HG and non-PRT group. TG patients had no evident improvement in MDADI and TP after surgery. There was a higher risk of swallowing unsafety with abnormal WST outcome in TG (P < 0.001, OR = 106.52) than that in HG. VFSS analysis identified prolonged oral and pharyngeal transit time, disorganized swallowing sequence, abnormal hyoid bone movement, and frequent invalid swallows in patients with TG. A shortened OTT (<5066.50 ms) and a larger pharyngeal constriction ratio (PCR > 0.31) were associated with increased risks of penetration and aspiration. CONCLUSION: Postoperative swallowing pattern is a characteristic of severely impaired safety and efficacy in patients with TG. Impaired OTT and PCR are variables that should be examined when determining the need for rehabilitation treatment.

The oral cancer microbiome contains tumor space-specific and clinicopathology-specific bacteria.

The crosstalk between the oral microbiome and oral cancer has yet to be characterized. This study recruited 218 patients for clinicopathological data analysis. Multiple types of specimens were collected from 27 patients for 16S rRNA gene sequencing, including 26 saliva, 16 swabs from the surface of tumor tissues, 16 adjacent normal tissues, 22 tumor outer tissue, 22 tumor inner tissues, and 10 lymph nodes. Clinicopathological data showed that the pathogenic bacteria could be frequently detected in the oral cavity of oral cancer patients, which was positively related to diabetes, later T stage of the tumor, and the presence of cervical lymphatic metastasis. Sequencing data revealed that compared with adjacent normal tissues, the microbiome of outer tumor tissues had a greater alpha diversity, with a larger proportion of Fusobacterium, Prevotella, and Porphyromonas, while a smaller proportion of Streptococcus. The space-specific microbiome, comparing outer tumor tissues with inner tumor tissues, suggested minor differences in diversity. However, Fusobacterium, Neisseria, Porphyromonas, and Alloprevotella were more abundant in outer tumor tissues, while Prevotella, Selenomonas, and Parvimonas were enriched in inner tumor tissues. Clinicopathology-specific microbiome analysis found that the diversity was markedly different between negative and positive extranodal extensions, whereas the diversity between different T-stages and N-stages was slightly different. Gemella and Bacillales were enriched in T1/T2-stage patients and the non-lymphatic metastasis group, while Spirochaetae and Flavobacteriia were enriched in the extranodal extension negative group. Taken together, high-throughput DNA sequencing in combination with clinicopathological features facilitated us to characterize special patterns of oral tumor microbiome in different disease developmental stages.