The association of dietary glutamine supplementation with the development of high salt-induced hypertension in rats.

Glutamine supplementation has been reported to affect blood pressure (BP). However, its role in the progression of hypertension induced by high salt diet (HSD) has not been elucidated. Male normotensive Wistar rats were exposed to high salt diet and treated with different doses of glutamine supplementation. Rats aged 6 weeks were assigned to five groups: (1) Normal-salt diet (0.3% NaCl, NSD); (2) High-salt diet (8% NaCl, HSD); (3) High-salt + low-dose diet (8% NaCl, 0.5 g of L-glutamine/kg body weight, HSLGD); (4) High-salt + middle-dose diet (8% NaCl, 1.5 g of L-glutamine/kg body weight, HSMGD); and (5) High-salt + high-dose diet (8% NaCl, 2.5 g of L-glutamine/kg body weight, HSHGD). After supplementing different doses of glutamine to male Wistar 6-week-old rats fed with HSD for 7 weeks, we found no difference in body weight among groups. Importantly, we showed that dietary L-glutamine supplementation could prevent the development of hypertension in a dose-dependent manner [dramatically lowering systolic blood pressure (SBP) and slightly reducing diastolic blood pressure (DBP) of hypertensive rats, while the differences of DBP between groups did not reach statistical significance]. Our data further elucidated that dietary glutamine supplementation mildly alleviated the degree of left ventricular hypertrophy, including interventricular septal thickness (IVST) and left ventricular posterior wall thickness (LVPWT) in hypertensive rats. Together, our results offer evidence that the dietary uptake of glutamine may be associated with attenuating the development of high salt-induced hypertension and slightly alleviating the degree of left ventricular hypertrophy in hypertensive rats. Therefore, glutamine supplementation may act as a prospective dietary intervention for the treatment of hypertension.

Baicalin regulates autophagy to interfere with small intestinal acute graft-versus-host disease.

Acute graft-versus-host disease (aGVHD) is the main complication of and cause of death after allogeneic hematopoietic stem cell transplantation. Baicalin can protect the small intestinal epithelial cells of rats against TNF-α-induced injury and alleviate enteritis-related diarrhea. To verify whether baicalin can protect the small intestinal mucosal barrier by regulating abnormal autophagy and interfering with intestinal aGVHD, a mouse model of aGVHD was established. CB6F1 micewere intravenously injected with a suspension of mononuclear cells derived from BALB/c donor mouse bone marrow and splenic tissue after treatment with 60Co X-rays. After treatment with different doses of baicalin for 15 days, the survival time, serum TNF-α and IL-10 levels, and autophagy markers levels in the intestine were assessed. A cell model of intestinal barrier dysfunction was also used to verify the effect of baicalin. The results showed that baicalin significantly prolonged the survival time, significantly reduced the aGVHD pathology score and clinical score by decreasing the TNF-α level with increasing the IL-10 level compared with the control. Transmission electron microscopy examination showed that baicalin treatment increased the number of autophagic vacuoles and led to the recovery of mitochondrial structures in the intestinal mucosal epithelial cells of mice and in Caco-2 cells. Western blotting results showed that baicalin treatment enhanced autophagy in vivo by regulating the AMPK/mTOR autophagy pathway. Similar results were observed in vitro in Caco-2 cells. Furthermore, the effect of baicalin was reduced after combination treatment with the autophagy inhibitor 3-methyladenine(3-MA). Baicalin can decrease the severity of small intestinal aGVHD by regulating autophagy by influencing imbalances in inflammatory cytokine levels and mucosal barrier damage, thus baicalin may have potential as a new treatment for aGVHD.

Identification of an immune subtype predicting survival risk and immune activity in hepatocellular carcinoma.

Immune checkpoint inhibitors (ICI) prolong the survival for advanced/metastatic patients with lung cancer or melanoma; however, for hepatocellular carcinoma (HCC) patients, a durable response has not been reported. Herein, we used a total of 719 HCC patients with public genomic data to determine potential prognostic and immunogenic subtypes. The non-negative matrix factorization (NMF) method was applied to identify the immune classes and potential subtypes. The proportion of tumor infiltration immune cells was estimated using the CIBERSORT algorithm. Gene set enrichment analysis (GSEA) was utilized to calculate the dysregulated pathways. By using NMF analysis for the gene expression profile of the top immune genes, one HCC subtype with better survival (i.e., low-risk subtype) and another with worse survival (i.e., high-risk subtype) were identified in 3 HCC cohorts (all P < 0.05). Better immune cell infiltration, increased enrichment of immune signatures, higher expression of checkpoints, and elevated tumor mutation load (TML) were significantly enriched in the low-risk subtype (all P < 0.05). Higher mutation rates of immune response genes (e.g., TP53 and MUC16) were also observed in the low-risk subtype (both P < 0.05). Discovery of the HCC low-risk subtype might provide clues for HCC prognosis and immunotherapy prediction.