SuanZaoRen decoction amliorates mitochondrial dysfunction of APP/PS1 mice via activating AMPK/SIRT1/PGC-1α signaling pathway / 中国药理学通报

Aim To explore the effect of Suanzaoren decoction(SZRD) on mitochondrial dysfunction in AD model of APP/PS1 mice via AMPK/SIRT1/PGC-1α signaling pathway and to reveal the possible mechanism. Methods Thirty APP/PS1 mice were randomly divided into app /PS1 group, low-dose SZRD group(L-SZRD) and high-dose SZRD group(H-SZRD). Ten C57BL/6JNju mice were set as control group(WT). Morris water maze test was used to detect the learning and memory ability of mice. Thioflavin T staining was used to observe senile plaques hippocampus. Immunohistochemistry was performed to detect the expression level of Aβ in hippocampus. Transmission electron microscope was used to observe the mitochondrial morph hology in hippocampus. Kits were employed to detect the contents of ATP and ROS in hippocampus; Western blot was employed to detect the expression levels of AMPK, p-AMPKThrK172, SIRT1, PGC-1α, NRF1, NRF2 and TFAM in hippocampus. Results Compared to the APP/PS1 group, L-SZRD and H-SZRD induced mouse cognitive impairment, reduced the deposition of senile plaques, inhibited the expression of Aβ, improved the damage of mitochondrial structure, increased the content of ATP in the hippocampus, reduced the expression level of ROS in hippocampus and increased the expression of p-AMPK-ThrK172, SIRT1, PGC-1α, NRF1, NRF2, TFAM Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Reduced the Deposition of Senile Plaques, Inhibited the Expression of Aβ, Improved The Damage of Mitochondric Structure, Increased the Content of At in TH. E hippocampus, Reduced the Expression level of Ros in Hippocampus and Increased The Expression of P-Ampk-Thrk172, SIRT1, SIRT1 PGC-1α, NRF1, NRF2, TFAM. Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Reduced the Deposition of Senile Plaques, Inhibited the Expression of Aβ, Improved The Damage of Mitochondric Structure, Increased the Content of At in TH. E hippocampus, Reduced the Expression level of Ros in Hippocampus and Increased The Expression of P-Ampk-Thrk172, SIRT1, SIRT1 PGC-1α, NRF1, NRF2, TFAM. Conclusions SZRD could improve the cognitive impairment, senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.Senile plaque deposition and mitochondrial dysfunction of AD mice, and its mechanism may be involved in the up-regulation of the expression of AMPK/SIRT1/PGC-1α signaling pathway.

Pain control for patients with hepatocellular carcinoma undergoing CT-guided percutaneous microwave ablation.

BACKGROUND: Hepatic percutaneous microwave ablation (MWA) is usually performed in patients under conscious sedation. Nonetheless, many patients reported pain during the procedure. The current study investigated the safety and effectiveness of analgesia given at personalized dosage during the MWA procedure. METHODS: A total of 100 patients with hepatocellular carcinomas (HCCs) were included in this study. These patients underwent CT-guided percutaneous MWA between February and October 2017. Patients were randomized into two groups: Experimental group (n = 50) and Control group (n = 50). Patients in the Control group were given 5 mg of morphine intravenously, followed by 10 mg of morphine injected subcutaneously 30 min before surgery. Patients in the Experimental group were given a personalized dosage of morphine during the procedure when the Visual Analogue Scale (VAS) was ≥4. Other clinical and treatment parameters were also analysed. RESULTS: A significantly less amount of morphine (p < 0.001) was used in the experimental group (7.18 ± 1.65 mg) than in the control group (17.40 ± 2.52 mg). No significant differences were found in the number of patients who needed to discontinue the surgery (p = 0.242). Other clinical parameters including heart rate, systolic and diastolic blood pressures at various time points were comparable. Importantly, a lower VAS was reported in the experimental group, indicating a lower pain intensity experienced by patients during the procedure. CONCLUSION: The administration of personalized dosage of morphine to HCC patients undergoing percutaneous MWA is an effective and safe procedure for pain control.

SMC1A knockdown induces growth suppression of human lung adenocarcinoma cells through G1/S cell cycle phase arrest and apoptosis pathways in vitro.

SMC1A (structural maintenance of chromosomes 1A), which encodes a structural subunit of the cohesin protein complex, is necessary for the process of sister chromatid cohesion during the cell cycle. Mutation and deregulation of SMC1A are highly relevant to diverse human diseases, including Cornelia de Lange syndrome and malignant carcinomas. In order to further investigate the role of SMC1A in the oncogenesis of lung cancer, SMC1A-specific short hairpin RNA (shRNA)-expressing lentivirus (Lv-shSMC1A) was constructed and used to infect A549 and H1299 cells. SMC1A mRNA and protein expression levels were downregulated in A549 and H1299 cells as demonstrated by real-time PCR and western blot assays. We found that SMC1A inhibition resulted in significantly impaired proliferation and colony formation as well as reduced invasiveness of tumor cells. Notably, Lv-shSMC1A-infected cancer cells exhibited a greater proportion of cells in the G0/G1 phase, but a lower proportion of S phase cells, compared to the parent or Lv-shCon infected cancer cells. Moreover, a greater proportion of sub-G1 apoptotic cells was observed in Lv-shSMC1A-infected cells. These results suggest that SMC1A is a novel proliferation regulator that promotes the growth of lung cancer cells, and that down-regulation of SMC1A expression induces growth suppression of A549 and H1299 cells via G1/S cell cycle phase arrest and apoptosis pathways. Therefore, SMC1A may serve as a new molecular target for lung cancer therapy.

MED19 promotes proliferation and tumorigenesis of lung cancer.

MED19 is a subunit of Mediator that is an essential component of RNA polymerase II-mediated transcription machinery. High expression levels of MED19 were examined in human lung adenocarcinoma tissues by immunohistochemical assay. MED19-specific short hairpin RNA (shRNA) expressing lentivirus was constructed and infected lung cancer cell line A549. MED19 mRNA and protein expression levels were downregulated in A549 cells as evidenced by real-time PCR and western blot assays. Importantly, MED19 inhibition resulted in impaired proliferation and colony formation, and induced accumulation of G1-phase cells and mitigated invasiveness of cells. More importantly, downregulation of MED19 expression reduced the tumorigenicity of A549 cells in vivo. It was suggested that MED19 is a novel proliferation regulator that promotes growth of lung cancer cells, thereby indicating that MED19 may serve as a new molecular target for lung cancer therapy.

[Perioperative management and follow-up of bariatric surgery for severe obesity].

Compared with general patients undergoing surgery, the patients with severe obesity are often accompanied by obesity-related diseases, which calls for more evaluation and preparation at full-scale. This article mainly illuminates the perioperative procedure of diagnosis and treatment, the preoperative evaluation and preparation performed by other related departments, and the postoperative management and follow-up for severe obesity patients.