Ginsenoside-Rg1 inhibits endoplasmic reticulum stress-induced apoptosis after unilateral ureteral obstruction in rats.

AIM: Endoplasmic reticulum (ER) stress and unfolded protein response (UPR) are implicated in many fibrotic diseases, including renal fibrosis. Whether Ginsenoside-Rg1 (G-Rg1) could attenuate renal fibrosis via suppression of ER stress and UPR has not been reported. The aim of this study was to explore the effect of G-Rg1 on ER stress and UPR-induced apoptosis in kidneys with unilateral ureteral obstruction (UUO) rat model. METHODS: Twenty-four male Sprague-Dawley rats were randomly divided into control group, model group and G-Rg1 treatment group. G-Rg1 was administered to rats by intraperitoneal injection. Renal interstitial fibrosis in the model group was developed by UUO in rats. Renal function was estimated by the levels of serum creatinine (Scr) and blood urea nitrogen (BUN). Renal pathological damage was evaluated by hematoxylin and eosin (HE) and Masson's trichrome staining. The ER stress was assessed with glucose-regulated protein (GRP) 78 expression, and the proapoptotic response was detected with CCAAT/enhancer-binding protein homologous protein (CHOP) and caspase-12 expressions by Western Blot. The number of apoptotic cells was determined by Terminal-deoxynucleotidyl Transferase Mediated Nick End Labeling (TUNEL) analysis. RESULTS: UUO for 14 days aggravated renal function, renal damage and renal interstitial fibrosis, activated ER stress response (induction of GRP78 protein), enhanced the proapoptotic response (increase in CHOP and caspase-12 proteins) and increased the number of apoptotic cells (shown by the TUNEL assay). Treatment with G-Rg1 significantly ameliorates the renal pathological lesions and decreases expressions of ER stress-associated proteins and the level of apoptotic cells in kidneys. CONCLUSION: G-Rg1 suppresses renal cell apoptotic and fibrotic process partly through inhibition of ERS- and UPR-related apoptotic pathway in the kidneys after UUO.

Nomogram to predict postoperative complications in elderly with total hip replacement.

BACKGROUND: By analyzing the risk factors of postoperative complications in elderly patients with hip replacement, We aimed to develop a nomogram model based on preoperative and intraoperative variables and verified the sensitivity and specificity for risk stratification of postoperative complications in elderly with total hip replacement patients. AIM: To develop a nomogram model for risk stratification of postoperative complications in elderly with total hip replacement patients. METHODS: A total of 414 elderly patients who underwent surgical treatment for total hip replacement hospitalized at the Affiliated Hospital of Guangdong Medical University from March 1, 2017 to August 31, 2019 were included into this study. Univariate and multivariate logistic regression were conducted to identify independent risk factors of postoperative complication in the 414 patients. A nomogram was developed by R software and validated to predict the risk of postoperative complications. RESULTS: Multivariate logistic regression analysis revealed that age (OR = 1.05, 95%CI: 1.00-1.09), renal failure (OR = 0.90, 95%CI: 0.83-0.97), Type 2 diabetes (OR = 1.05, 95%CI: 1.00-1.09), albumin (ALB) (OR = 0.91, 95%CI: 0.83-0.99) were independent risk factors of postoperative complication in elderly patients with hip replacement (P < 0.05). For validation of the nomogram, receive operating characteristic curve revealed that the model predicting postoperative complication in elderly patients with hip replacement was the area under the curve of 0.8254 (95%CI: 0.78-0.87), the slope of the calibration plot was close to 1 and the model passed Hosmer-Lemeshow goodness of fit test (χ 2 = 10.16, P = 0.4264), calibration in R Emax = 0.176, Eavg = 0.027, which all demonstrated that the model was of good accuracy. CONCLUSION: The nomogram predicting postoperative complications in patients with total hip replacement constructed based on age, type 2 diabetes, renal failure and ALB is of good discrimination and accuracy, which was of clinical significance.

Dexmedetomidine hydrochloride inhibits hepatocyte apoptosis and inflammation by activating the lncRNA TUG1/miR-194/SIRT1 signaling pathway.

BACKGROUND: Liver injury seriously threatens the health of people. Meanwhile, dexmedetomidine hydrochloride (DEX) can protect against liver injury. However, the mechanism by which Dex mediates the progression of liver injury remains unclear. Thus, this study aimed to investigate the function of DEX in oxygen and glucose deprivation (OGD)-treated hepatocytes and its underlying mechanism. METHODS: In order to investigate the function of DEX in liver injury, WRL-68 cells were treated with OGD. Cell viability was measured by MTT assay. Cell apoptosis was detected by flow cytometry. Inflammatory cytokines levels were measured by ELISA assay. The interaction between miR-194 and TUG1 or SIRT1 was detected by dual-luciferase reporter. Gene and protein levels were measured by qPCR or western blotting. RESULTS: DEX notably reversed OGD-induced inflammation and apoptosis in WRL-68 cell. Meanwhile, the effect of OGD on TUG1, SIRT1 and miR-194 expression in WRL-68 cells was reversed by DEX treatment. However, TUG1 knockdown or miR-194 overexpression reversed the function of DEX in OGD-treated WRL-68 cells. Moreover, TUG1 could promote the expression of SIRT1 by sponging miR-194. Furthermore, knockdown of TUG1 promoted OGD-induced cell growth inhibition and inflammatory responses, while miR-194 inhibitor or SIRT1 overexpression partially reversed this phenomenon. CONCLUSIONS: DEX could suppress OGD-induced hepatocyte apoptosis and inflammation by mediation of TUG1/miR-194/SIRT1 axis. Therefore, this study might provide a scientific basis for the application of DEX on liver injury treatment.

How to prevent in-hospital COVID-19 infection and reassure women about the safety of pregnancy: Experience from an obstetric center in China.

OBJECTIVE: This study aimed to describe the emergency responses to coronavirus disease 2019 (COVID-19) for pregnant patients at our hospital and their effect on hospital operations and patients' outcomes. METHODS: We developed strategies to prevent hospital-associated transmission of COVID-19 in obstetric care. Infrastructure, including the fever clinic and wards, were modified. Outpatient volume was controlled and screening processes were strictly performed. Verification of the virus was compulsory for non-surgery and non-emergency patients. Emergency operations were performed in a negative pressure theater with surgeons fully protected. Outcomes were analyzed and the patients' characteristics were evaluated. The effect of intervention on depressed and anxious patients was assessed. Data from the first 2 months of 2019 and 2020 were compared. RESULTS: No in-hospital COVID-19 infections occurred in our unit. During the epidemic, patient volume significantly decreased. While major characteristics of patients were similar, a higher prevalence of gestational hypertension was found in 2020 than in 2019. Psychological interventions showed optimistic effects in ameliorating depression and anxiety at the beginning of the COVID-19 pandemic. CONCLUSIONS: Our strategies were effective in preventing in-hospital infection of COVID-19 and reassuring women about the safety of pregnancy. Monitoring and managing psychological issues were necessary during this critical period.

Association of Soluble Klotho Level with Adverse Outcomes in Patients on Maintenance Hemodialysis.

BACKGROUND: The predictive value of soluble Klotho (sKlotho) for adverse outcomes in patients on maintenance hemodialysis (MHD) is controversial. In this study, we aimed to clarify the potential association of sKlotho levels with adverse outcomes in this patient population. MATERIALS: A total of 211 patients on MHD were identified and stratified according to the median sKlotho level. Patients were followed up for adverse outcomes including cardiovascular (CV) morbidity and all-cause mortality. RESULTS: During the 36-month follow-up, 75 patients [51 CV events (including 16 CV deaths) and 40 deaths] experienced adverse outcomes. After stratification according to median sKlotho level, patients with a lower sKlotho level had a greater risk of CV events (38.2% vs. 19.5%, p = 0.006), all-cause mortality (28.4% vs. 11.6%, p = 0.003), and combined adverse outcomes (51.0% vs. 24.2%, p < 0.001). Similar observations were made from analyses using Kaplan-Meier survival curves. Cox regression analysis showed that a low sKlotho level was strongly correlated with CV morbidity [1.942 (1.030-3.661), p = 0.040)], all-cause mortality [2.073 (1.023-4.203), p = 0.043], and combined adverse outcomes [1.818 (1.092-3.026), p = 0.021] in fully adjusted models. CONCLUSIONS: The sKlotho level was an independent predictive factor of adverse outcomes including CV morbidity and mortality in patients on MHD.

Natural Products and Derivatives Targeting at Cancer Energy Metabolism: A Potential Treatment Strategy.

In the 1920s, Dr Otto Warburg first suggested the significant difference in energy metabolism between malignant cancer cells and adjacent normal cells. Tumor cells mainly adopt the glycolysis as energy source to maintain tumor cell growth and biosynthesis under aerobic conditions. Investigation on energy metabolism pathway in cancer cells has aroused the interest of cancer researchers all around the world. In recent years, plentiful studies suggest that targeting the peculiar cancer energy metabolic pathways, including glycolysis, mitochondrial respiration, amino acid metabolism, and fatty acid oxidation may be an effective strategy to starve cancer cells by blocking essential nutrients. Natural products (NPs) are considered as the "treasure trove of small molecules drugs" and have played an extremely remarkable role in the discovery and development of anticancer drugs. And numerous NPs have been reported to act on cancer energy metabolism targets. Herein, a comprehensive overview about cancer energy metabolism targets and their natural-occurring inhibitors is prepared.

Yangfei Kongliu Formula, a compound Chinese herbal medicine, combined with cisplatin, inhibits growth of lung cancer cells through transforming growth factor-ß1 signaling pathway.

OBJECTIVE: To investigate the tumor inhibition effect of Yangfei Kongliu Formula (YKF), a compound Chinese herbal medicine, combined with cisplatin (DDP) and its action mechanisms. METHODS: C57BL/6 mice with Lewis lung carcinoma were divided into six groups: control group (C), DDP group (2 mg/kg, DDP), low-dose YKF group (2.43 g/kg, L), high-dose YKF group (24.3 g/kg, H), low-dose YKF combined with DDP group (L + DDP) and high-dose YKF combined with DDP group (H + DDP). Transforming growth factor-ß1 (TGF-ß1), mothers against decapentaplegic homolog 3 (Smad3) and Smad7 levels were measured with quantitative real-time polymerase chain reaction (qPCR), Western blotting and immunohistochemistry. An enzyme-linked immunosorbent assay was used to analyze the expressions of interleukin-2 (IL-2) and tumor necrosis factor-α (TNF-α). RESULTS: YKF combined with DDP significantly inhibited the growth and metastasis of tumors relative to the control group, and YKF groups (P < 0.05). There was no significant difference between high-dose YKF group and low-dose YKF group (P > 0.05). We also found that the expression levels of TGF-ß1 and Smad3 were both significantly decreased by YKF relative to the control group (P < 0.05). Furthermore, after treatment with YKF combined with DDP, the expression levels of TGF-ß1 and Smad3 were decreased but the expression level of Smad7 was increased relative to the DDP group (P < 0.05). Compared to the DDP group, the combination of YKF and DDP enhanced the effect of tumor inhibition (P < 0.05), showing obvious synergy between YKF and DDP. Treatment with DDP or YKF decreased serum levels of IL-2 and TNF-α relative to the control group (P < 0.05). Furthermore, the expression levels of IL-2 and TNF-α were significantly decreased when treated with YKF in combination with DDP. Co-treatment with YKF and DDP significantly inhibited tumor growth, decreased the expressions of TGF-ß1, Smad3, IL-2 and TNF-α and increased the expression of Smad7; these differences were significant relative to both YKF groups and the control group (P < 0.05). CONCLUSION: YKF can inhibit tumor growth synergistically with DDP, mainly through the TGF-ß1 signaling pathway.

Klotho mitigates cyclosporine A (CsA)-induced epithelial-mesenchymal transition (EMT) and renal fibrosis in rats.

PURPOSE: Klotho deficiency is implicated in various kidney diseases, including renal fibrosis. The aim of this study was to investigate the effect of Klotho administration on epithelial-mesenchymal transition (EMT) and renal fibrosis induced by cyclosporine A (CsA) in rats. METHODS: CsA-induced renal fibrosis was established by oral administration of CsA (30 mg/kg) to rats on a low-salt diet for 28 days. Klotho was administered to rats by intraperitoneal injection. Renal pathological changes were evaluated by hematoxylin and eosin and Masson's trichrome staining. The EMT response was assessed by measuring the level of TGF-ß1, E-cadherin and α-SMA by immunohistochemistry and Western blot. RESULTS: Administration of CsA for 28 days induced renal damage, decreased Klotho expression and activated the EMT response (demonstrated as increased TGF-ß1 and α-SMA expression accompanied by decreased in E-cadherin expression). Treatment with Klotho significantly ameliorated pathological lesions of the kidney by modulating the expression of EMT-associated proteins in the kidney. CONCLUSIONS: Klotho inhibits CsA-induced EMT and renal fibrosis in rats. Klotho may serve as a therapeutic agent to minimize CsA-induced renal fibrosis.