One anastomosis gastric bypass ameliorates diabetic nephropathy via regulating the GLP-1-mediated Sirt1/AMPK/PGC1α pathway.

BACKGROUND: Diabetic nephropathy (DN), a complication of diabetes, is the most leading cause of end-stage renal disease. Bariatric surgery functions on the remission of diabetes and diabetes-related complications. One anastomosis gastric bypass (OAGB), one of popular bariatric surgery, can improve diabetes and its complications by regulating the glucagon-like peptide-1 (GLP-1) level. Meanwhile, GLP-1 can alleviate renal damage in high-fat-diet-induced obese rats. However, the effect of OAGB on renal injury remains uncertain in DN. METHODS: A diabetes model was elicited in rats via HFD feeding and STZ injection. The role and mechanism of OAGB were addressed in DN rats by the body and kidney weight and blood glucose supervision, oral glucose tolerance test (OGTT), enzyme-linked immunosorbent assay (ELISA), biochemistry detection, histopathological analysis, and western blot assays. RESULTS: OAGB surgery reversed the increase in body weight and glucose tolerance indicators in diabetes rats. Also, OAGB operation neutralized the DN-induced average kidney weight, kidney weight/body weight, and renal injury indexes accompanied with reduced glomerular hypertrophy, alleviated mesangial dilation and decreased tubular and periglomerular collagen deposition. In addition, OAGB introduction reduced the DN-induced renal triglyceride and renal cholesterol with the regulation of fatty acids-related proteins expression. Mechanically, OAGB administration rescued the DN-induced expression of Sirt1/AMPK/PGC1α pathway mediated by GLP-1. Pharmacological block of GLP-1 receptor inverted the effect of OAGB operation on body weight, glucose tolerance, renal tissue damage, and fibrosis and lipids accumulation in DN rats. CONCLUSION: OAGB improved renal damage and fibrosis and lipids accumulation in DN rats by GLP-1-mediated Sirt1/AMPK/PGC1α pathway.

Long Non-Coding RNA BCAR4 Promotes Oxaliplatin Resistance in Colorectal Cancer by Modulating miR-484-3p/RAB5C Expression.

BACKGROUND: Oxaliplatin-based chemotherapy resistance is a major cause of recurrence in patients with colorectal cancer (CRC). Increasing evidence indicates that lncRNA BCAR4 is involved in the occurrence and development of various cancers. However, the effect of BCAR4 on CRC chemotherapy resistance remains unclear. METHODS: Real-time quantitative PCR and Western blotting were used to detect the expression levels of gene and protein, respectively. The role of BCAR4 in drug resistance was evaluated by cell viability and apoptosis experiments. Luciferase reporter assay and Western blot analysis confirmed the relationship between BCAR4, miR-483-3p, and RAB5C. RESULTS: Luciferase reporter assay and Western blotting analysis confirmed the relationship among BCAR4, miR-483-3p, and RAB5C. The results showed that the expression levels of BCAR4 and RAB5C were increased in CRC tumor tissue. The expression levels of BCAR4 were increased in patients with chemotherapy resistance. Functional analysis showed that knockdown of BCAR4 reduced the expression levels of proteins related to stemness, decreased the activity of cells, and promoted apoptosis of CRC cells, while overexpression of RAB5C reversed these effects. Moreover, the results showed that BCAR4 promoted oxaliplatin resistance by inhibiting cell apoptosis. Mechanistically, BCAR4 sponged miR-483-3p and promoted the expression of RAB5C. Knockdown of BCAR4 reduced tumor size and enhanced cell sensitivity to oxaliplatin in vivo. CONCLUSION: The results suggested that BCAR4/miR-483-3p/RAB5C axis has the potential to be explored as a novel therapeutic target for CRC treatment.

Efficacy and Safety of One Anastomosis Gastric Bypass Versus Roux-en-Y Gastric Bypass for Obesity: a Meta-analysis and Systematic Review.

The objective of this review is to systematically review the efficacy and safety outcomes of one anastomosis gastric bypass (OAGB) with Roux-en-Y gastric bypass (RYGB). From inception to July 4, 2022, a systematic literature search was performed using PubMed, Embase, and Cochrane Library for randomized clinical trials comparing OAGB with RYGB in obesity. A meta-analysis performed using the RevMan 5.4.1 software evaluations was completed. We identified 1217 reports; after exclusions, eight trials with a total of 931 patients were eligible for analysis. Compared with RYGB, OAGB had multiple advantageous indexes. Examples include percent of excess weight loss (%EWL) at 12 months (P = 0.009), body mass index (BMI) at 2 years (P < 0.00001), early postoperative complication (P = 0.04), remission of dyslipidemia (P < 0.0001), and operative time (P < 0.00001). No significant statistical difference was observed in BMI at 6 months, %EWL at 6 months, BMI at 12 months, percent of excess body mass index loss (%EBMIL) at 2 years, BMI at 5 years, intraoperative complications, late postoperative complications, remission of type 2 diabetes mellitus, and dyslipidemia or gastroesophageal reflux disease remission between OAGB and RYGB. OAGB is no less effective than RYGB; no significant differences in weight loss efficacy were observed, and more large and long-term randomized controlled trials are needed to verify this. In addition, studies have shown that OAGB has a shorter operation time, fewer early postoperative complications, and a shorter learning curve, making it easier for young surgeons to perform.

LncRNA BCAR4, targeting to miR-665/STAT3 signaling, maintains cancer stem cells stemness and promotes tumorigenicity in colorectal cancer.

BACKGROUND: Breast cancer anti-estrogen resistance 4 (BCAR4) is closely associated with colorectal cancer (CRC) initiation and propagation. However, the mechanisms underlying BCAR4 function in colon cancer remains largely unknown. In this study, we hypothesized that BCAR4 could regulate colon cancer stem/initiating cells (CSC) function and further facilitates the colon cancer progression. METHODS: qRT-PCR was used to examine the expression of BCAR4 and various CSC markers. FACS, acetaldehyde dehydrogenase (ALDH) activity and western blot assays were applicable to test the expression of CSC markers. CCK8, tumorsphere formation and transwell assays were adopted to examine the capacity of CRC cells proliferation, self-renewal and migration. Pull down assay was used to test the interaction between BCAR4 and miR-665. Luciferase reporter assay was used to examine the interaction of miR-665 and activators of transcription (STAT3). In vivo tumor xenograft study was used to verify the malignancy of CRC cells with inhibition of BCAR4. RESULTS: Breast cancer anti-estrogen resistance 4 was highly expressed in both CRC cells and stem/initiating cells. In addition, overexpression of BCAR4 facilitated the maintenance of ALDH positive cells (a type of cancer stem/initiating cells) stemness and promoted ALDH+ cells proliferation and migration. Inhibition of BCAR4 restricted ALDH+ cells proliferation and migration. We further proved that miR-665 was the target of BCAR4 and subsequently activated signal transducers and STAT3 signaling which is an important pathway in cancer stem cells self-renewal. CONCLUSIONS: Breast cancer anti-estrogen resistance 4 promotes the CRC cells stemness through targeting to miR-665/STAT3 signaling and identification of the BCAR4 in CRC stem cells provides a new insight into CRC diagnosis, treatment, prognosis and next-step translational investigations.

LncRNA BCAR4 promotes colon cancer progression via activating Wnt/ß-catenin signaling.

BCAR4 (Breast Cancer Anti-Estrogen Resistance 4) is a long noncoding RNA that was identified as an oncogene in breast cancer. In our research, we found that the expression level of BCAR4 was upregulated in colon cancer tissues compared to paired normal tissues. What's more, higher BCAR4 expression was correlated with lower survival rate in patients with colon cancer. Mechanistically, we showed that BCAR4 activated Wnt/ß-catenin signaling in colon cancer by protecting ß-catenin from degradation. We also showed that BCAR4 overexpression promoted cell proliferation and migration in colon cancer. However, silencing BCAR4 inhibited cell growth and promoted apoptosis. Besides, BCAR4 knockdown decreased tumor growth in vivo. These findings indicate that BCAR4 facilitated colon cancer progression by enhancing cell proliferation and inhibiting apoptosis via BCAR4/ß-catenin axis. BCAR4 may be a useful new target for treatment of patients with colon cancer.

The application of nutrition support in conservative treatment of chylous ascites after abdominal surgery.

BACKGROUND: Chylous ascites is the pathologic leakage of triglycerides-rich lymphatic fluid into the peritoneal cavity. Chylous ascites is a rare complication in abdominal surgery. This study aimed to find a relatively better method for nutrition support in the treatment of chylous ascites after abdominal surgery. METHODS: This study was a retrospective study. This study retrospectively reviewed patients who underwent abdominal surgery and developed chylous ascites, from the year 2010 to 2014, at the West China Hospital of Sichuan University and the Affiliated Hospital of Zunyi Medical College. Fifty-eight patients who developed chylous ascites after abdominal surgery were included in the study. The clinical effect of somatostatin was evaluated. The differences in the curative efficacy among a daily diet, a low-fat diet supplemented with medium-chain triglyceride (MCT), and total parenteral nutrition (TPN) were also analyzed in this study. RESULTS: Complete clinical success was reached earlier in patients treated with somatostatin (P<0.001). The tube removal time, the time to resumption of an oral diet, and the length of hospital stay after chylous leakage were significantly different between patients treated with and without somatostatin. The curative efficacies of the enteral nutrition (EN) + MCT plan and the TPN plan were quite similar, with no significant difference, however, were significantly different from the MCT regime, which was the worst. However, using the EN + MCT plan was more cost-effective (P=0.038). CONCLUSION: In treating chylous ascites, EN + MCT instead of TPN was the best nutrition support. Moreover, somatostatin or its analog octreotide should be used immediately. The treatment with somatostatin in combination with EN + MCT is recommended in the conservative treatment of postoperative chylous ascites.

[Use of inflammatory factors combined with multi-slice spiral computer tomography for preoperative staging and operative strategy in colon cancer].

OBJECTIVE: To determine the clinical value of C-reactive protein(CRP), fibrinogen (FIB), or serum amyloid A protein (SAA) combined with 64 multi-slice computed tomography (MSCT) for preoperative staging and operative strategy in colon cancer. METHODS: Patients with colon cancer were prospectively enrolled at the West China Hospital of Sichuan University from November 2007 to July 2009,and were equally randomized into 3 groups undergoing different preoperative evaluation: MSCT combined with CRP(CRP group), MSCT combined with FIB (FIB group), and MSCT combined with SAA (SAA group). The agreement between preoperative staging and postoperative pathologic staging and that between expected surgical procedure and procedure adopted were compared. RESULTS: Baseline characteristics among three groups were similar(P>0.05). In CRP group, the accuracies of preoperative staging T, N, M and TNM were 65.7%, 72.4%, 100% and 66.7%, respectively. In FIB group, the accuracies of preoperative staging T, N, M and TNM were 71.4%, 74.3%, 99.0% and 65.7%, respectively. In SAA group, the accuracies of preoperative staging T, N, M and TNM were 60.0%, 55.2%, 96.2%and 51.4%, respectively. The accuracies of N and TNM staging in CRP group and FIB group were significantly higher than those in SAA group(P<0.05). However, there were no significant differences between FIB and CRP group(P>0.05). There were no significant differences in accuracy of predicting surgical procedures among three groups(93.3%, 92.3% and 87.6%, P>0.05). CONCLUSION: Combined assessment of MSCT and CRP or FIB may improve the accuracy of preoperative staging and procedure prediction, and is superior to MSCT combined with SAA.