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Type 2 diabetes mellitus (T2DM) is a metabolic disease controlled by a combination of genetic and environmental factors. The Chinese hamster, as a novel animal model of spontaneous T2DM with high phenotypic similarity to human disease, is of great value in identifying potential therapeutic targets for T2DM. Here, we used tandem mass tag (TMT) quantitative proteomics based on liquid chromatography-tandem mass spectrometry to assess the skeletal muscles of a Chinese hamster diabetes model. We identified 38 differentially abundant proteins, of which 14 were upregulated and 24 were downregulated. Further analysis of the differentially abundant proteins revealed that five of them (OPLAH, GST, EPHX1, SIRT5, ALDH1L1) were associated with oxidative stress; these were validated at the protein and mRNA levels, and the results were consistent with the proteomic analysis results. In addition, we evaluated the role of OPLAH in the pathogenesis of T2DM in human skeletal muscle cells (HSKMCs) by silencing it. The knockdown of OPLAH caused an increase in reactive oxygen species content, decreased the GSH content, inhibited the PI3K/Akt/GLUT4 signaling pathway, and reduced glucose uptake. We propose that OPLAH downregulation plays a role in insulin resistance and glucose uptake disorders in HSKMCs possibly via oxidative stress, making it a new therapeutic target for T2DM. [Display omitted] • Proteomics used to assess skeletal muscles of Chinese hamster diabetes model. • 38 differentially abundant proteins, including 14 upregulated and 24 downregulated. • Five of these (OPLAH, GST, EPHX1, SIRT5, ALDH1L1) associated with oxidative stress. • OPLAH role in T2DM pathogenesis in human skeletal muscle cells (HSKMCs) evaluated. • OPLAH knockdown increased ROS and blocked GSH, glucose uptake, and PI3K/Akt/GLUT4. [ABSTRACT FROM AUTHOR]

ABSTRACT Background Stress-induced hyperglycaemia ( SHG) can be observed in as high as 75% of critically ill patients, which can induce severe complications or adverse events. However, conventional intensive insulin therapy ( CIIT) tends to induce hypoglycaemia and glucose variability. Aims This study investigated the clinical effects of a blood glycaemic control optimization programme ( BGCOP) in patients with stress hyperglycaemia post hepatobiliary or pancreatic surgery. Design This study is a randomized, controlled, prospective clinical observation. Methods Eighty-six patients with postoperative SHG were randomly divided into a control and experimental groups. Participants in the control group underwent CIIT, while participants in the experimental group underwent blood glycaemic control optimization programme (BGCOP). A range of 7·8-10·0 mmol/L was designated as the target range for effective control of blood sugar. The validity index, adverse events and complications were compared between two groups. Results Compared to participants treated with CIIT, participants treated with BGCOP reached the target range of blood sugar levels more quickly ( p = 0·000). The high glycaemic index ( p = 0·000), incidence of hypoglycaemia ( p = 0·011), and other adverse events as well as the incidence of abdominal infection ( p = 0·026), incision infection ( p = 0·044), and lung infection ( p = 0·047) were significantly lower in participants who underwent the BGCOP than in patients treated with CIIT. Conclusion BGCOP can more effectively control blood sugar levels compared with CIIT in patients with SHG after hepatobiliary or pancreatic surgery. Relevance to clinical practice This study provides a direction for blood glycaemic control in patients with stress hyperglycaemia post hepatobiliary or pancreatic surgery. [ABSTRACT FROM AUTHOR]

Non-obese, spontaneous, and genetically predisposed type 2 diabetic Chinese hamsters exhibit metabolic abnormalities similar to those observed in human T2DM. Here, tandem mass tag (TMT)-based quantitative proteomics technology was used to screen and identify differentially abundant proteins in the liver that are associated with diabetes in Chinese hamsters. GO and KEGG pathway enrichment analysis were conducted to validate the findings, as well as qRT-PCR and western blotting. In total, 103 proteins were identified in the livers of diabetic hamsters, of which 48 were up-regulated and 55 were down-regulated. KEGG pathway enrichment analysis further demonstrated that linoleic acid metabolism, arachidonic acid metabolism, bile secretion, and other pathways were affected. Moreover, AQP9 and EPHX1 were significantly down-regulated in the bile secretion pathway, whereas PTGES2, Cyp2c27, and Cyp2c70 were associated with the arachidonic acid metabolic pathway. Serum levels of bile acid (BA) and arachidonic acid (AA) in diabetic Chinese hamsters were significantly higher than those in control hamsters. Cumulatively, our findings indicate that the five candidate proteins may be associated with abnormal BA and AA metabolism, suggesting their involvement in pathological changes in the livers of Chinese hamsters with T2DM. The liver proteomics of Chinese hamsters describes differentially abundant proteins associated with T2DM, while promoting this animal model as an appropriate and ideal platform for investigating underlying molecular mechanisms of T2DM. This study reveals abnormal bile acid and arachidonic acid metabolism in T2DM hamsters, which may provide insights for studying the relationship between candidate proteins and KEGG pathways to elucidate the underlying molecular mechanism associated with T2DM. [Display omitted] • Quantitative proteomics of livers in spontaneous type 2 diabetic Chinese hamsters • 103 proteins were identified between control and diabetic hamsters. • 5 proteins involved in bile secretion and arachidonic acid metabolism were verified. • Abnormal metabolism of bile acid and arachidonic acid in vivo [ABSTRACT FROM AUTHOR]

Introduction: To explore the relationship between the composite dietary antioxidant index (CDAI) and gout to provide support for preventing gout through dietary intervention. Methods: Eligible participants from the 2007 to 2018 National Health and Nutrition Examination Survey aged 20 years and older were included in this cross-sectional study. The weighted chi-square test was used to compare the categorical variables difference between CDAI quartiles groups. The weighted univariate and binary logistic regression analysis were used to test the association between variables and gout. The weighted multivariable logistic regression was used to test the association of CDAI and gout in 4 different models. Subgroup analysis on the associations of CDAI with gout was conducted with stratified factors. Results: The final participants were 26,117, 13,103 (50.17%) were female, 8718 (33.38%) were 40–59 years, 11,200 (42.88%) were white and 1232 (4.72%) had gout. After adjusting for all covariates, the CDAI was associated with gout (odds ratio (OR),.97; 95% CI:.95–1.00). Participants in the highest CDAI quantile group were at low risk of gout (odds ratio (OR),.65; 95% CI:.50–.84) versus those in the lowest quantile group. Subgroup analysis and interaction test showed no significant dependence on diabetes mellitus (DM), marital status, alcohol status, hypertension, poverty income ratio (PIR), education level, body mass index (BMI), smoke status, age, sex, race, and chronic kidney disease (CKD) on this association (all p for interaction >.05). Conclusions: Composite dietary antioxidant index was inversely associated with gout in US adults, and dietary antioxidant intervention might be a promising method in the therapy of gout and greater emphasis should be placed on zinc, selenium, carotenoids, vitamins A, C, and E. [ABSTRACT FROM AUTHOR]

Long non-coding RNAs (lncRNAs) serve important roles in colorectal cancer. The aim of the present study was to investigate the expression and role of cervical carcinoma expressed PCNA regulatory (CCEPR) lncRNA in colorectal cancer progression. The results demonstrated that CCEPR expression was significantly higher in colorectal cancer tissues when compared with paired adjacent normal tissues. In addition, CCEPR expression was significantly higher in patients with advanced colorectal cancer (stage III/IV) than those with early-stage colorectal cancer (stage I/II). High CCEPR expression was significantly associated with poor differentiation, advanced clinical stage, positive lymph node metastasis and distant metastasis. Of particular note, patients with colorectal cancer exhibiting high CCEPR expression levels had shorter survival rates when compared with patients with low CCEPR expression. In vitro experiments demonstrated that the expression of CCEPR was increased in colorectal cancer cell lines when compared with a normal colon cell line. Knockdown of CCEPR significantly inhibited colorectal cancer cell proliferation, colony formation and cell cycle progression, as well as cell migration and invasion. Finally, silencing of CCEPR downregulated matrix metalloproteinase (MMP)-2 and MMP-9 expression and suppressed epithelial-mesenchymal transition in colorectal cancer cells. In conclusion, the results of the present study suggest that CCEPR may exert an oncogenic role in colorectal cancer, and CCEPR may be a promising molecular target for colorectal cancer treatment. [ABSTRACT FROM AUTHOR]

Bone metastasis is the main cause of death in patients with prostate cancer (PCa), but there lacks effective treatment method. Immunotherapy shows new hopes for bone metastatic PCa patients, while the efficacy is still unsatisfactory and limited by the unique immunosuppressive microenvironment in metastatic bone site. Here, we developed a bone-targeted nano-delivery system as a nano-regulator to enhance the immunotherapy of bone metastatic PCa. The nanosystem was assembled via coordination between phytic acid (PA) and Fe3+ to form nano-sized metal–organic framework (MOF), through which mitoxantrone (MTO) was encapsulated. At cellular level, the nanosystem showed selective cytotoxicity towards RM-1 PCa cells over immune cells, and could induce tumor cells immunogenic cell death (ICD) to improve the immunogenicity of the tumor. Moreover, the nanosystem was able to induce ubiquitination of TGFβ receptor (TβR) on immune cells to promote its degradation, thus serving as a nano-regulator to block the functions of TGF-β, an abundant cytokine that has a systematically immunosuppressive effect in the tumor microenvironment. Upon intravenous injection, the nanoparticle showed pro-longed blood circulation and targeting accumulation into bone metastatic site, and imposed robust anti-tumor effect in combination with αCTLA-4. In addition, bone destruction was significantly alleviated after treatment to reduce the skeletal-related events. Overall, this work provides a biocompatible nanomedicine to restore immune sensitivity of bone metastatic tumor for enhanced immunotherapy by blocking TGF-β signaling pathway. [ABSTRACT FROM AUTHOR]

Pressure ulcer (PU), also called pressure injury, is localized damage to the skin and underlying soft tissues, usually over bony prominences, as a result of sustained mechanical loads applied to the tissues. However, in many situations, complete off-loading of sacral PUs is not possible. Minimising the exposure of wounds and their surroundings to elevated mechanical loads is crucial for healing. We for the first time reported the application of Meipicang in the prevention and treatment of intraoperative pressure ulcers in elderly ICU patients with severe illness. We found that the pressure ulcer risk score (20.15 ± 2.17) in the dressing group after intervention was higher than that (17.42 ± 3.62) in the regular group. The incidence of pressure sores in the dressing group was 3.77% lower than the 18.88% in the regular group. The psychological concern score (31.41 ± 3.15) of the dressing group was higher than that (26.92 ± 3.43) of the regular group. The trust score (29.57 ± 2.61) of the dressing group was higher than the score (24.28 ± 2.29) of the regular group. The score of physiological problems in the dressing group (34.69 ± 3.82) is higher than that in the regular group (29.88 ± 3.54). The skin complication rate of the dressing group was 5.56% lower than that of the regular group (22.64%). The comfort score (92.46 ± 4.15) of the dressing group was higher than that (80.59 ± 5.43) of the regular group. The nursing satisfaction score (94.53 ± 3.72) of the dressing group was higher than that (81.79 ± 4.61) of the regular group. To conclude, in this study, we found that the Meipicang dressing can reduce the incidence of pressure ulcers in ICU patients with severe ICU and improve the comfort and nursing satisfaction of elderly ICU patients with severe ICU, which is worthy of promotion. [ABSTRACT FROM AUTHOR]

Aim: The preoperative poor nutrition of children with congenital heart disease (CHD) impacts the postoperative rehabilitation process of pediatric CHD cases. The factors of these children's preoperative poor nutrition, excluding the disease, have been underreported. The aim was to investigate the preoperative nutritional status of children with CHD who required a simple surgical repair and to analyze the maternal characteristics that are associated with poor nutrition in these sick children. Methods: This was a cross‐sectional survey. The weight and height of the children were measured, maternal data were collected via a questionnaire and a univariate analysis and multivariate logistic regression were used to analyze the association between maternal factors and the preoperative poor nutrition of the children with CHD. Results: A total of 119 children with simple CHD were recruited to the study. The prevalence of poor nutrition was higher in the children with CHD ("cases") than in the healthy children ("controls"). An increased risk of poor nutrition was associated with lower mothers' perception, education level, understanding of the disease, and higher anxiety. Conclusions: Paying attention to maternal anxiety, depression, and knowledge and providing interventions for the mothers of children with CHD are important in order to promote the nutritional status of these children. [ABSTRACT FROM AUTHOR]

HClO is recognized as an indicator for phagocytosis and inflammatory response. Excess HClO ruptures lysosomes and leads to cell apoptosis, which has been proposed as a cure for cancer treatment. As a consequence, the real-time and in situ cell imaging for HClO is highly appealed in the field of anticancer pharmacy. In this work, a series of silane-modified rhodamine fluorescers with various functional groups were designed, hoping to find a fluorescer with near IR emission for bio-imaging in live cells, along with unique sensing response towards ClO− over competing species. These silane-modified rhodamine fluorescers were carefully characterized, their photophysical parameters and responses towards ClO− and competing species were compared systematically. An optimal probe showed emission quantum yield of 0.26 with emission wavelength at 681 nm. Emission "turn-on" effect was observed, with calibration equation of F = 0.720*[ClO−]2+40.047*[ClO−]+54.982, R2 = 0.999, and the limit of detection (LOD) was calculated as 0.03 μM. Corresponding sensing mechanism was revealed as an HClO-mediated cyclization reaction. Fluorescence imaging for Hela cells and A549 lung cancer cells was performed. The lysosome-targetable feature was confirmed. • A series of silane-modified rhodamine fluorescers with near IR emission for bio-imaging in live cells were reported. • An optimal probe showed emission quantum yield of 0.26 with emission wavelength at 681 nm. • Sensing calibration equation was a non-linear one and the limit of detection (LOD) was calculated as 0.03 μM. • Sensing mechanism was revealed as an HClO-mediated cyclization reaction. [ABSTRACT FROM AUTHOR]

This study demonstrated that miR-21 and miR-95 expression were significantly higher in the ALDH1+CD133+subpopulation than in the ALDH1-CD133- subpopulation of lung cancer cells. Combined delivery of anti-miR-21 and anti-miR-95 by calcium phosphate nanoparticles significantly inhibited tumor growth in a xenograft tumor model and sensitized radiotherapy. The anti-miRNAs significantly reduced miR-21 and miR-95 levels, increased PTEN, SNX1, and SGPP1 protein expression, but reduced Akt Ser473 and Thr308 phosphorylation. ALDH1+CD133+ subpopulation of NSCLC tumor cells confers radioresistance due to high expression of miR-21 and miR-95. Targeting inhibition of miR-21 and miR-95 can inhibit tumor growth through elevating PTEN, SNX1, and SGPP1 expression and inhibiting Akt phosphorylation. [ABSTRACT FROM AUTHOR]

Type 2 diabetes mellitus (T2DM) is a metabolic disorder characterized by hyperglycemia, with metabolic disturbances resulting from defects in insulin secretion, insulin resistance (IR), or both. Chinese hamsters have potential value as non-obese animal models of spontaneous T2DM for studying the pathogenesis and molecular characteristics of diabetes. In this study, the molecular characteristics of the Chinese hamster diabetes animal model were investigated through small intestine proteomics and serum metabolomics. A total of 213 differentially abundant proteins and 14 differentially abundant metabolites were identified through liquid chromatography-tandem mass spectrometry (LC-MS/MS) and gas chromatography-time of flight mass spectrometry (GC-TOF/MS) analysis, respectively. Annotation by bioinformatics analysis revealed that these differentially abundant proteins in the small intestine were commonly associated with abnormal glucose and lipid metabolism, IR, impaired insulin secretion, amino acid metabolism disorders, and inflammatory dysregulation. Moreover, differentially abundant metabolites in the serum were amino acids and were related to diabetic IR. Through the analysis of small intestine proteomics and serum metabolomics in the Chinese hamster diabetes model, we provide a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. This study provides data incentivizing the popularization and application of Chinese hamsters in T2DM research. Spontaneous rodent models of diabetes, such as Chinese hamsters, effectively summarizes the clinical characteristics of type 2 diabetes and has high applicative value for studying the pathophysiology of diabetes. In order to explore the potential value of the Chinese hamster diabetes animal model in the study of the T2DM molecular mechanism, we performed small intestine proteomic analysis and serum metabolomic analysis in Chinese hamsters for the first time. After an integrated analysis of proteomics and metabolomics, we have a preliminary understanding of the diabetic characteristics of this model from a molecular perspective. Further, we found that in the occurrence and development of T2DM, the metabolic abnormalities of this model are particularly prominent, especially the metabolism of amino acids. These findings not only provide basic data in support of the popularization and application of the current model in T2DM research, but also provide a new perspective for the exploration of mechanisms related to T2DM. Unlabelled Image • Chinese hamsters diabetes model has high application value in the study of type 2 diabetes. • The differentially abundant proteins were related to glucose and lipid metabolism, amino acid metabolism, IR and inflammatory disorders in diabetes. • The results of metabolomics suggested that the amino acid metabolism of diabetic Chinese hamsters was abnormal. [ABSTRACT FROM AUTHOR]