[Mild hypothermia combined with hydrogen sulfide alleviates hippocampal endoplasmic reticulum stress after global cerebral ischemia-reperfusion].

Objective: To investigate the effect of mild hypothermia combined with hydrogen sulfide on hippocampal endoplasmic reticulum stress (ERS) after global cerebral ischemia-reperfusion (I/R) injury. Methods: Sixty healthy male Sprague-Dawley rats, 8-10 week old, weighing 280-320 g, were randomly divided into 5 groups (n=12) using a random number table: sham operation group (group Sham), global cerebral I/R group (group I/R), hydrogen sulfide group (group H(2)S), mild hypothermia group (group MH) and hydrogen sulfide + mild hypothermia group (group H(2)S+ MH). Cardiac arrest was induced with transoesophageal cardiac pacing followed by cardiopulmonary resuscitation to establish the global cerebral I/R model. The administration regimen for sodium hydrosulfide (NaHS) was as follows: Sodium hydrosulfide was intraperitoneal injection as a bolus of 2.5 mg/kg immediately restoration of spontaneous circulation. The implementation of mild hypothermia: wipe the body surface of rats with ethanol immediately after restoration of spontaneous circulation, and reduce the rectal temperature to 32-34 ℃ within 15 min, and maintain 6 h with the ice bag. At 72 h of reperfusion, neurological deficit was scored, and the rats were sacrificed (Neurological Deficit Scores, NDS), the expression of glucose-regulated protein 78 (GRP78), CHOP and Caspase-12 were detected by Western blot. After reperfusion 72 h, the hippocampal tissue were removed and stained with haematoxylin and eosin to examine the pathological findings in hippocampal CA1 area (under microscope). The apoptosis rate of hippocampal CA1 area cells was detected by TUNEL staining and the apoptosis index was calculated. Results: The expression levels of endoplasmic reticulum stress marker, GRP78, CHOP and Caspase-12, were upregulates during the global cerebral ischemia reperfusion injury, indicating activation of severe endoplasmic reticulum stress. The GRP78 contents of Sham group, I/R group, H(2)S group, MH group and H(2)S+ MH group were as follows: GRP78: 0.11±0.03, 1.11±0.10, 0.67±0.09, 0.66±0.08, 0.48±0.04, CHOP contents: 0.16±0.03, 1.60±0.11, 1.39±0.09, 1.34±0.08, 1.13±0.09, Caspase-12 contents: 0.09±0.02, 0.87±0.08, 0.65±0.08, 0.59±0.06, 0.45±0.06, the differences were statistically significant (F=147.569, 264.983, 119.356, all P<0.01). The apoptosis index of Sham group, I/R group, H(2)S group, MH group and H(2)S+ MH group were as follows: (1.83±0.75)%, (53.17±4.62)%, (35.17±2.14)%, (32.67±2.25)%, (17.83±2.79)%, the differences were statistically significant (F=284.962, P<0.01). The neurological deficit scores of Sham group, I/R group, H(2)S group, MH group and H(2)S+ MH group were as follows: 0%, (76±9)%, (54±5)%, (47±6)%, (35±6)%, the differences were statistically significant(F=135.218, P<0.01). Conclusion: Mild hypothermia combined with hydrogen sulfide alleviates hippocampal endoplasmic reticulum stress after global cerebral ischemia-reperfusion, and the combined effect is better than that of a single application.

Well-balanced commensal microbiota contributes to anti-cancer response in a lung cancer mouse model.

The intestinal microflora affects inflammation and immunity, not only locally at the mucosal level but also systemically, raising the question of whether the microflora affects inflammatory processes that contribute to cancer and its therapy. Prebiotics have also been found to play an antitumor role that is not limited to the gut. We investigated the antitumor roles of the intestinal microbiota using the Lewis lung cancer mouse model. In mice treated with cisplatin combined with ABX (an antibiotic cocktail of vancomycin, ampicillin, and neomycin), which can destroy the host commensal microflora, the tumor size was larger than in mice on a single treatment of cisplatin. Moreover, the survival rate of mice treated with cisplatin combined with ABX was significantly reduced. In contrast, mice treated with cisplatin combined with Lactobacillus bacteria had smaller tumors and an improved survival rate. Further study on gene expression indicated that ABX can partially impair the function of cisplatin by upregulating the expression of VEGFA and downregulating the expression of BAX and CDKN1B. The expression of IFN-γ, GZMB, and PRF1 in the CD8(+) T cells of these mice was reduced by ABX, indicating an immuno-enhancement role of commensal microbiota. Conversely, Lactobacillus co-treatment mice showed an enhanced antitumor response with upregulated IFN-γ, GZMB, and PRF1 expression. We conclude that the commensal microbiota contributes to the anti-lung cancer response and probiotics co-treatment can enhance the antigrowth and proapoptotic effects of cisplatin.