Novel subtype of obesity influencing the outcomes of sleeve gastrectomy: Familial aggregation of obesity.

BACKGROUND: Differences in the preoperative characteristics and weight loss outcomes after sleeve gastrectomy (SG) between patients with familial aggregation of obesity (FAO) and patients with sporadic obesity (SO) have not been elucidated. AIM: To explore the impact of SG on weight loss and the alleviation of obesity-related comorbidities in individuals with FAO. METHODS: A total of 193 patients with obesity who underwent SG were selected. Patients with FAO/SO were matched 1:1 by propensity score matching and were categorized into 4 groups based on the number of first-degree relatives with obesity (1SO vs 1FAO, 2SO vs 2FAO). The baseline characteristics, weight loss outcomes, prevalence of obesity-related comorbidities and incidence of major surgery-related complications were compared between groups. RESULTS: We defined FAO as the presence of two or more first-degree relatives with obesity. Patients with FAO did not initially show significant differences in baseline data, short-term postoperative weight loss, or obesity-related comorbidities when compared to patients with SO preoperatively. However, distinctions between the two groups became evident at the two-year mark, with statistically significant differences in both percentage of total weight loss (P = 0.006) and percentage of excess weight loss (P < 0.001). The FAO group exhibited weaker remission of type 2 diabetes mellitus (T2DM) (P = 0.031), hyperlipidemia (P = 0.012), and non-alcoholic fatty liver disease (NAFLD) (P = 0.003) as well as a lower incidence of acid reflux (P = 0.038). CONCLUSION: FAO patients is associated with decreased mid-to-long-term weight loss outcomes; the alleviation of T2DM, hyperlipidemia and NAFLD; and decreased incidence of acid reflux postoperatively.

Resveratrol Inhibits Abdominal Aortic Aneurysm Progression by Reducing Extracellular Matrix Degradation, Apoptosis, Autophagy, and Inflammation of Vascular Smooth Muscle Cells via Upregulation of HMOX1.

OBJECTIVE: This study aimed to explore the therapeutic effect of resveratrol (RES) against abdominal aortic aneurysm (AAA) and the role of HMOX1 underlying this effect. METHODS: Vascular smooth muscle cells (VSMCs) were induced by angiotensin II (Ang II) to construct the microenvironment of AAA. HMOX1 expression was downregulated by the short hairpin ribonucleic acid (RNA) specific to HMOX1 in RES-pretreated VSMCs. The levels of matrix metalloproteinase (MMP)-2, MMP-9, and elastin were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR) and western blot. Apoptosis rate was detected. The levels of apoptosis-related proteins (caspase-3 and Bax/Bcl-2), inflammatory cytokines (interleukin [IL]-6, tumor necrosis factor [TNF]-α, and IL-1ß), and autophagy-related proteins (Beclin 1, light chain 3 [LC3] II/I, and p62) were detected by western blot. The secretion of inflammatory factors in cell supernatant was detected by enzyme-linked immunosorbent assay (ELISA). The number of autophagic vesicles in VSMCs was observed and analyzed by transmission electron microscopy. A rat model of pancreatic elastase-induced AAA was established to verify the effect and action mechanism of RES. RESULTS: Stimulation of Ang II increased the messenger RNA (mRNA) and protein levels of MMP-2 and MMP-9, decreased elastin expression, and enhanced apoptosis, secretion of inflammatory factors, and autophagy in VSMCs, whereas RES pretreatment ameliorated Ang II-induced VSMC dysfunction. In addition, HMOX1 mRNA and heme oxygenase-1 (HO-1) protein levels were significantly increased in VSMCs pretreated with RES compared with Ang II treatment alone. Silencing of HMOX1 abolished the effects of RES on VSMC dysfunction. Consistently, RES suppressed the development of AAA in rats by increasing the expression of HMOX1. CONCLUSION: Resveratrol protects against AAA by inhibiting extracellular matrix degradation, apoptosis, autophagy, and inflammation of VSMCs via HMOX1 upregulation. CLINICAL IMPACT: Our study found that angiotensin II (Ang II) stimulated increased the levels of MMP-2 and MMP-9 in vascular smooth muscle cells (VSMCs), decreased elastin expression, and promoted apoptosis, autophagy occurrence, and secretion of inflammatory factors, while resveratrol (RES) pretreatment improved this effect. In addition, downregulation of HMOX1 expression eliminated the effect of RES on the function of VSMCs. Our study elucidates that RES improves AAA progression through HMOX1 at both cellular and animal levels. This work can help doctors better understand the pathological mechanism of the occurrence and development of AAA, and provide a theoretical basis for clinicians to find better treatment options.

Upconversion luminescence properties and optical thermometry based on non-thermal coupling levels of Ho3+, Yb3+, and Tm3+ codoped 12CaO·7Al2O3 single crystals.

Compared with the fluorescence intensity ratio (FIR) temperature measurement technology based on the thermal coupling levels (TCLs) of rare earth (RE) ions, non-TCL (NTCL) FIR technology can greatly improve temperature measurement sensitivity because it is not limited by Boltzmann distribution. In this paper, a H o 3+/Y b 3+/T m 3+ co-doped 12C a O⋅7A l 2 O 3 (C12A7) single crystal was grown by the Czochralski method. As the temperature increased from 363 K to 523 K, the upconversion luminescence color of the H o 3+/Y b 3+/T m 3+/C12A7 crystal changed from white to yellow, and exhibited a large temperature dependence under 980 nm excitation. In the temperature range of 363-523 K, the FIR temperature measurement based on different NTCLs exhibited high temperature sensitivity; the maximum absolute sensitivity and relative sensitivity values were 0.0207K -1 and 2.82% K -1, respectively, which are higher than those previously reported based on TCLs of H o 3+ and T m 3+. This provides a strategy to achieve accurate sensitivity of FIR technology. The RE ion doped C12A7 single crystal material has good research and application prospects in the field of temperature sensing and optoelectronics.

A preliminary study on the anxiety and depression situation and psychological intervention of the first-line medical staff in our hospital during the COVID-19 epidemic.

To assess the anxiety and depression situation and psychological intervention effect of the first-line medical staff in our hospital during the COVID-19 epidemic. A total of 384 front-line medical staff in our hospital from January 25 to March 8, 2020 were selected as subjects, which were divided into group A and group B respectively. PHQ-9 depression scale and GAD-7 self-rating anxiety scale questionnaire were used to investigate their anxiety and depression. After 1 month, all subjects were re-self-assessed for anxiety and depression, which were named as A1 and B1 group respectively. The GAD-7 anxiety scale had mild, moderate, and severe anxiety scores before group A, which were significantly higher than those in group B (P < 0.05); after psychological intervention, group A1 had significantly reduced anxiety scores (P < 0.05). And there were no markedly difference of PHQ-9 scale scores before and after psychological intervention between groups A and B, A and A1, and B and B1 (P > 0.05). The first-line medical staff in our hospital have different degree of anxiety and depression during COVID-19. Early positive psychological intervention has an effect on ameliorating the anxiety.

Clickable amino acid derivative tuned self-assembly of antigen and adjuvant for cancer immunotherapy.

Amino acid-tuned self-assembly has become an attractive strategy for constructing various functional materials. Here, a series of dibenzocyclooctyne (DIBO) functionalized amphiphilic amino acid derivatives are designed and screened as building blocks of functional supramolecular self-assembly nanoparticles for cancer immunotherapy. One top-performing supramolecular self-assembly material (named DA6C1) is identified through combinatorial screening, and spherical nanoparticles can be easily prepared by this material tuned multicomponent synergistic self-assembly of ovalbumin (OVA) and CpG oligonucleotide. DA6C1 based nanovaccine can significantly enhance the cellular uptake of OVA and CpG into the same bone marrow derived dendritic cells (BMDCs) and greatly improve the activation of DCs. Moreover, after subcutaneous injection, this nanovaccine flows rapidly to the lymph nodes and elicits strong immune responses to achieve effective prophylactic and therapeutic effect. Therefore, our work highlights the great potential of clickable amino acid derivatives as a convenient and powerful tool to construct nanovaccine for effective immunotherapy.

Sodium butyrate ameliorates non-alcoholic fatty liver disease by upregulating miR-150 to suppress CXCR4 expression.

Sodium butyrate (NaB) in the gut of animals possesses the potential to modulate lipid metabolism, regulate innate immunity and protect intestinal health. Accumulating data have supported the important function of metabolites of intestinal microflora (MIM) in non-alcoholic fatty liver disease (NAFLD). This study intended to investigate the role of NaB in NAFLD and its specific mechanism. Mice were fed a high-fat diet (HFD) for 16 weeks to establish the NAFLD mouse model. The mice were intragastrically administrated MIM (200 µL/day) or NaB (200 mg/kg/day) by gavage for another 8 weeks. The morphology of liver tissues was observed by hematoxylin and eosin (H&E) staining, and the lipid deposition of liver tissues was examined by oil red O staining. The NAFLD cell model was constructed in alpha mouse liver 12 (AML12) cells by 24 hours of stimulation with 0.5 mM free fatty acids. After treatment with 10 mM NaB, AML12 cells were transfected with mimic-miR-150 or inhibitor-miR-150. Quantitative real-time polymerase chain reaction (qRT-PCR) and western blotting were used to measure the contents of interleukin 1ß (IL-1ß), IL-6 and tumour necrosis factor α (TNF-α) and the expression of microRNA (miR)-150 and CXCR4 in liver tissues of mice and in AML12 cells. A luciferase reporter assay was applied to verify the binding relationship between miR-150 and CXCR4. The H&E and oil red O staining results showed hepatic steatosis in the liver tissues of HFD-fed mice. There were elevated contents of triacylglycerides (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), fasting blood glucose, enhanced activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST), increased homeostatic model assessment of insulin resistance scores and increased inflammatory responses in the serum of HFD-fed mice. However, intervention with MIM or NaB reversed the above trends, indicating that MIM or NaB intervention relieved hepatic steatosis in mice. HFD-fed mice had downregulated expression of miR-150, whereas the expression level was upregulated after MIM or NaB treatment. Sodium butyrate attenuated NAFLD progression by regulating miR-150. MiR-150 can negatively target CXCR4. Sodium butyrate mitigates HFD-induced NAFLD in mice by upregulating miR-150 expression to downregulate CXCR4.

Interference of Hsa_circ_0003928 Alleviates High Glucose-Induced Cell Apoptosis and Inflammation in HK-2 Cells via miR-151-3p/Anxa2.

BACKGROUND: Diabetic nephropathy (DN) is a severe end-stage kidney disease developed from diabetes mellitus. The involvement of circular RNA (circRNAs) in the regulation of DN pathogenesis has been implied, but the underlying mechanism of DN is still lacking. This study aimed to investigate the effect of hsa_circ_0003928 on the inflammation and apoptosis of high glucose (HG)-induced renal tubular cells. METHODS: The expression of hsa_circ_0003928, miR-151-3p and Anxa2 in blood samples from DN patients and healthy controls was detected by RT-qPCR. Human renal epithelial cells HK-2 were incubated with D-glucose (30 mmol/l) to establish DN model in vitro. RT-qPCR analysis confirmed the transfection effects and detected the expressions of TNF-α, IL-6 and IL-1ß. Western blotting analysis determined the protein expression of Anxa2, Bcl-2, Bax, cleaved caspase-3 and caspase-3. The production of ROS was detected by DCF-DA method and production of inflammatory cytokines was verified by ELISA assay. CCK-8 assay and TUNEL assay were performed to determine cell viability and apoptosis, respectively. Dual-luciferase reporter assay was performed to confirm the relationship between miR-151-3p and hsa_circ_0003928 or Anxa2. RESULTS: Hsa_circ_0003928 and Anxa2 mRNA levels were increased, whereas miR-151-3p was decreased in both HG-induced HK-2 cells and patients with DN. Hsa_circ_0003928 knockdown could decrease cell viability loss and apoptosis, increase Bcl-2 expression, and decrease Bax and cleaved caspase-3 expression. Besides, hsa_circ_0003928 knockdown suppressed HG-induced overproduction of ROS, TNF-α, IL-6 and IL-1ß. However, the effects made by miR-151-3p inhibition were opposite to those made by hsa_circ_0003928 knockdown. Furthermore, the binding sites between miR-151-3p and hsa_circ_0003928 or Anxa2 were predicted and verified. Protein expression of Anxa2 was suppressed by hsa_circ_0003928 knockdown, which was rescued by miR-151-3p inhibition. CONCLUSION: These results demonstrated that hsa_circ_0003928 could act as a sponge of miR-151-3p and regulate HG-induced inflammation and apoptosis partly through regulating Anxa2.

miR-365b-3p inhibits the cell proliferation and migration of human coronary artery smooth muscle cells by directly targeting ADAMTS1 in coronary atherosclerosis.

Abnormal proliferation and migration of vascular smooth muscle cells serves a crucial role in the development of atherosclerosis. Previous studies have suggested that some microRNAs (miRs) are involved in this process; however, the associated underlying molecular mechanism is unclear. In present study, human coronary artery smooth muscle cells (HCASMCs) were used to explore the function of miR-365b-3p in the coronary atherosclerosis. It was indicated that platelet-derived growth factor-BB (PDGF-BB) treatment inhibited miR-365b-3p expression and upregulated the expression of a disintegrin and metalloproteinase with thrombospondin motifs 1 (ADAMTS1) in HCASMCs. Subsequently, miR-365b-3p mimic was transfected in HCASMCs to explore the function of this miR. The results of reverse transcription-quantitative polymerase chain reaction and western blot analysis indicated that overexpression of miR-365b-3p significantly downregulated ADAMTS1 expression. Functional assay results revealed that overexpression of miR-365b-3p significantly attenuated PDGF-BB-induced proliferation and migration of HCASMCs. Furthermore, the dual-luciferase reporter assay results confirmed that ADAMTS1 is a direct target gene of miR-365b-3p. This discovery proposed a novel channel of communication between ADAMTS1 and HCASMCs, and suggests a potential therapeutic approach for coronary atherosclerosis.