Cerebellar gray matter and white matter damage among older adults with prediabetes.

AIMS: To investigate alterations in cerebrum and cerebellum in prediabetes. Cerebellar injury in diabetes is traceable, but it has not been systematically studied, and whether cerebellar injury occurs and the degree of damage in prediabetes are not known. METHODS: The current study investigated cerebral and cerebellar gray matter volume, white matter volume, white matter microstructure and white matter hyperintensity on T1-weighted, T2-weighted fluid-attenuated inversion recovery and diffusion tensor imaging scans in 78 individuals with normal glucose metabolism, 92 with prediabetes, and 108 with type 2 diabetes. RESULTS: Participants with prediabetes showed significant gray matter and white matter atrophy, microstructural damage in the cerebellar and cerebral regions. Additionally, widespread structural alterations were observed in the diabetic stage. The function of the damaged brain area was further decoded in Neurosynth, and the damaged cerebellar area with prediabetic lesions was closely related to motor function, while the area affected by diabetes was related to complex cognitive function in addition to motor function. CONCLUSIONS: Cerebellar injury had already appeared in the prediabetic stage, and cerebellar injury was aggravated in the diabetic stage; therefore, the cerebellum is a key area that is damaged early in the development of diabetes.

Identification of mitochondria-related biomarkers in childhood allergic asthma.

BACKGROUND: The mechanism of mitochondria-related genes (MRGs) in childhood allergic asthma (CAS) was unclear. The aim of this study was to find new biomarkers related to MRGs in CAS. METHODS: This research utilized two CAS-related datasets (GSE40888 and GSE40732) and extracted 40 MRGs from the MitoCarta3.0 Database. Initially, differential expression analysis was performed on CAS and control samples in the GSE40888 dataset to obtain the differentially expressed genes (DEGs). Differentially expressed MRGs (DE-MRGs) were obtained by overlapping the DEGs and MRGs. Protein protein interactions (PPI) network of DE-MRGs was created and the top 10 genes in the degree ranking of Maximal Clique Centrality (MCC) algorithm were defined as feature genes. Hub genes were obtained from the intersection genes from the Least absolute shrinkage and selection operator (LASSO) and EXtreme Gradient Boosting (XGBoost) algorithms. Additionally, the expression validation was conducted, functional enrichment analysis, immune infiltration analysis were finished, and transcription factors (TFs)-miRNA-mRNA regulatory network was constructed. RESULTS: A total of 1505 DEGs were obtained from the GSE40888, and 44 DE-MRGs were obtained. A PPI network based on these 44 DE-MRGs was created and revealed strong interactions between ADCK5 and MFN1, BNIP3 and NBR1. Four hub genes (NDUFAF7, MTIF3, MRPS26, and NDUFAF1) were obtained by taking the intersection of genes from the LASSO and XGBoost algorithms based on 10 signature genes which obtained from PPI. In addition, hub genes-based alignment diagram showed good diagnostic performance. The results of Gene Set Enrichment Analysis (GSEA) suggested that hub genes were closely related to mismatch repair. The B cells naive cells were significantly expressed between CAS and control groups, and MTIF3 was most strongly negatively correlated with B cells naive. In addition, the expression of MTIF3 and MRPS26 may have influenced the inflammatory response in CAS patients by affecting mitochondria-related functions. The quantitative real-time polymerase chain reaction (qRT‒PCR) results showed that four hub genes were all down-regulated in the CAS samples. CONCLUSION: NDUFAF7, MTIF3, MRPS26, and NDUFAF1 were identified as an MRGs-related biomarkers in CAS, which provides some reference for further research on CAS.

The knockdown of lncRNA DLGAP1-AS2 suppresses osteosarcoma progression by inhibiting aerobic glycolysis via the miR-451a/HK2 axis.

Osteosarcoma (OS) is one of the most aggressive bone tumors worldwide. Emerging documents have shown that long noncoding RNAs (lncRNAs) elicit crucial regulatory functions in the process of tumorigenesis. LncRNA DLGAP1-AS2 is recognized as a regulator in several types of cancers, but its biological functions and molecular mechanisms in OS remain to be elucidated. RT-qPCR and In situ hybridization (ISH) were used to evaluate DLGAP1-AS2 expression in OS samples. Western blotting was used for the measurement of the protein levels of hexokinase 2 (HK2) and epithelial-mesenchymal transition (EMT)-related markers. The proliferation of OS cells was determined using a CCK-8 assay and EdU assay. TUNEL assay and flow cytometry were performed to assess OS cell apoptosis. Glucose metabolism in vitro assays were used. The binding relations among miR-451a, HK2, and DLGAP1-AS2 were validated by luciferase reporter assay. The cellular distribution of DLGAP1-AS2 in OS cells was determined by FISH and subcellular fractionation assays. Mouse xenograft models were established to perform the experiments in vivo. We found that DLGAP1-AS2 expression was upregulated in OS tissues and cells. Downregulation of DLGAP1-AS2 expression suppressed the malignancy of OS cells by restraining cell proliferation, the EMT process, invasiveness, migration, and aerobic glycolysis and accelerating apoptotic behaviors. Of note, silenced DLGAP1-AS2 restrained tumor growth and metastasis in vivo. However, DLGAP1-AS2 overexpression accelerated the progression of OS. We further found that DLGAP1-AS2 upregulation was induced by hypoxia and low glucose. Additionally, DLGAP1-AS2 bound to miR-451a to upregulate HK2 expression. Rescue assays revealed that the DLGAP1-AS2/miR-451a/HK2 axis contributed to OS cell malignancy by promoting aerobic glucose metabolism. Overall, these findings revealed a new regulatory pathway where DLGAP1-AS2 upregulated HK2 expression by sponging miR-451a to accelerate OS development.

Acupuncture improved hepatic steatosis in HFD-induced NAFLD rats by regulating intestinal microbiota.

Background: Intestinal dysbiosis has been increasingly implicated in the pathogenesis of non-alcoholic fatty liver disease (NAFLD). Acupuncture has been shown to have beneficial effects on NAFLD, but the mechanism is not yet clear. This study explores the potential beneficial effects of acupuncture on intestinal microbiota in NAFLD. Methods: An NAFLD model in Sprague Dawley rats was established using a high-fat diet (HFD) for 10 weeks. NAFLD rats were randomly divided into control, model, and acupuncture groups. Following acupuncture treatment over 6 weeks, automated biochemical analysis was used to measure serum lipid metabolism parameters, including levels of alanine transferase, aspartate transferase, alkaline phosphatase, total cholesterol, triglycerides, high-density lipoprotein cholesterol, and low-density lipoprotein cholesterol. The level of serum inflammatory factors interleukin (IL)-6, IL-10, and tumor necrosis factor-alpha (TNF-α) were measured by enzyme-linked immunosorbent assay. The characteristics of steatosis were evaluated using quantitative computed tomography, hematoxylin and eosin staining, and Oil Red O staining in the liver, while the intestinal microbiota was determined using 16S rRNA gene sequencing. Results: Acupuncture decreased the systemic inflammatory response, ameliorated dyslipidemia, and improved liver function indexes in NAFLD model rats. Tomography and staining indicated that acupuncture reduced steatosis and infiltration of inflammatory cells in the liver. 16S rRNA analysis showed that acupuncture reduced the Firmicutes to Bacteroidetes (F/B) ratio, increased the abundance of microbiota, including Bacteroidales_S24-7_group, Prevotellaceae, Bacteroidaceae, Blautia, norank_f_Bacteroidales_S24-7_group, Bacteroides, and Prevotella_9, and decreased the abundance of Ruminococcaceae_UCG-014. Correlation analysis suggested a close correlation between lipid metabolism, inflammation factors, hepatic steatosis, and the changed intestinal microbiota. Conclusion: Acupuncture can significantly improve lipid metabolism and the systemic inflammatory response in HFD-induced NAFLD rats, potentially by regulating intestinal microbiota composition.

Understanding the research on tracking, diagnosing, and intervening in sleep disorders using mHealth apps: Bibliometric analysis and systematic reviews.

Objectives: In solving the global challenge of sleep disorders, Mobile Health app is one of the important means to monitor, diagnose, and intervene in sleep disorders. This study aims to (1) summarize the status and trends of research in this field; (2) assess the production and usage of sleep mHealth apps; (3) calculate the conversion rate of grants that the proportion of newly developed apps from being funded and developed to published on application stores. Methods: Using bibliometric and content analysis methods, based on "Research Paper-Product Output-Product Application" chain and considering the "Research Grants" of articles, we conducted a systematic review of eight databases, to identify relevant studies over the last decade. Results: Over the past decade, 1399 authors published 313 papers in 182 journals and conferences. The number of publications increased with an average annual growth of 41.6%. The current focus area is research using cognitive behavioral therapy to intervene in sleep. Sleep-staging tracking is a shortcoming of this field. A total 368 sleep mHealth apps (233 newly developed and 135 existing) were examined in 313 papers; 323 grants supported 178 articles (56.9%). Only 12 of the newly developed apps are used in the real world, resulting in a 9% grant conversion rate. Conclusions: In the last decade, the field of tracking, diagnosing, and intervening in sleep disorders using mHealth apps has shown a trend of rapid development. However, the conversion rate of products from being funded and developed for use by end-users is low.

Correlation between the Human Development Index and the Incidence and Mortality of Non-Hodgkin Lymphoma.

OBJECTIVE: This study was to examine the relationship between socioeconomic status and the incidence and mortality of non-Hodgkin lymphoma (NHL). METHODS: We compared the age-standardized incidence rate (ASIR), age-standardized mortality rate (ASMR), and the ASMR to ASIR ratio (MIR) at national and regional levels and studied the correlation between the MIR and the human development index (HDI) in 2012 and 2018. RESULTS: The highest ASIR was in North America in 2012 and in Australia in 2018, and the lowest ASIR was in Central and South Asia in both 2012 and 2018. The highest ASMR was in North Africa in both 2012 and 2018, and the lowest ASMR was in Eastern Asia and South-Central Asia in 2012 and in South-Central Asia in 2018. The lowest MIR was in Australia in both 2012 and 2018, and the highest MIR was in Western Africa in both 2012 and 2018. HDI was strongly negatively correlated with MIR (r: -0.8810, P<0.0001, 2012; r: -0.8895, P<0.0001, 2018). Compared to the 2012 data, the MIR in the intermediate HDI countries significantly deceased and the HDI in low and high HDI countries significantly increased in 2018. CONCLUSION: The MIR is negatively correlated with HDI. Increasing the HDI in low and intermediate HDI countries may reduce the MIR and increase the survival of patients with NHL.

Mining the Influencing Factors and Their Asymmetrical Effects of mHealth Sleep App User Satisfaction From Real-world User-Generated Reviews: Content Analysis and Topic Modeling.

BACKGROUND: Sleep disorders are a global challenge, affecting a quarter of the global population. Mobile health (mHealth) sleep apps are a potential solution, but 25% of users stop using them after a single use. User satisfaction had a significant impact on continued use intention. OBJECTIVE: This China-US comparison study aimed to mine the topics discussed in user-generated reviews of mHealth sleep apps, assess the effects of the topics on user satisfaction and dissatisfaction with these apps, and provide suggestions for improving users' intentions to continue using mHealth sleep apps. METHODS: An unsupervised clustering technique was used to identify the topics discussed in user reviews of mHealth sleep apps. On the basis of the two-factor theory, the Tobit model was used to explore the effect of each topic on user satisfaction and dissatisfaction, and differences in the effects were analyzed using the Wald test. RESULTS: A total of 488,071 user reviews of 10 mainstream sleep apps were collected, including 267,589 (54.8%) American user reviews and 220,482 (45.2%) Chinese user reviews. The user satisfaction rates of sleep apps were poor (China: 56.58% vs the United States: 45.87%). We identified 14 topics in the user-generated reviews for each country. In the Chinese data, 13 topics had a significant effect on the positive deviation (PD) and negative deviation (ND) of user satisfaction. The 2 variables (PD and ND) were defined by the difference between the user rating and the overall rating of the app in the app store. Among these topics, the app's sound recording function (ß=1.026; P=.004) had the largest positive effect on the PD of user satisfaction, and the topic with the largest positive effect on the ND of user satisfaction was the sleep improvement effect of the app (ß=1.185; P<.001). In the American data, all 14 topics had a significant effect on the PD and ND of user satisfaction. Among these, the topic with the largest positive effect on the ND of user satisfaction was the app's sleep promotion effect (ß=1.389; P<.001), whereas the app's sleep improvement effect (ß=1.168; P<.001) had the largest positive effect on the PD of user satisfaction. The Wald test showed that there were significant differences in the PD and ND models of user satisfaction in both countries (all P<.05), indicating that the influencing factors of user satisfaction with mHealth sleep apps were asymmetrical. Using the China-US comparison, hygiene factors (ie, stability, compatibility, cost, and sleep monitoring function) and 2 motivation factors (ie, sleep suggestion function and sleep promotion effects) of sleep apps were identified. CONCLUSIONS: By distinguishing between the hygiene and motivation factors, the use of sleep apps in the real world can be effectively promoted.

Sex differences in major cardiovascular outcomes and fractures in patients with subclinical thyroid dysfunction: a systematic review and meta-analysis.

OBJECTIVE: To evaluate whether sex differences in the associations of subclinical hypothyroidism (SH) and subclinical hyperthyroidism (SCH) with the risks of major adverse cardiovascular events (MACE) and fractures. METHODS: The PubMed, EmBase, and Cochrane Library databases were searched for eligible studies from inception until November 2021. The relative risk (RR) ratio with the 95% confidence interval (CI) was used to identify sex differences in the associations of SH and SCH with the risks of MACE and fractures. All analyses were performed using a random-effects model. RESULTS: Twenty-four cohort studies (in 3,480,682 patients) were selected for meta-analysis. There were no sex differences in the associations of SH and SCH with the risks of atrial fibrillation, all-cause mortality, cardiac death, coronary heart disease, heart failure, MACE, stroke, fracture. Subgroup analyses indicated a greater risk of MACE in men than in women with SH if follow-up was ≥10.0 years (RR ratio 2.44; 95% CI 1.17-5.10; P = 0.017). The risk of any fracture was greater in men than in women with SH if follow-up was <10.0 years (RR ratio 1.17; 95% CI 1.03-1.34; P = 0.017) and in studies with a high level of adjustment (RR ratio 1.16; 95% CI 1.02-1.32; P = 0.022). However, the risk of hip fracture was lower in men than in women with SH on pooling of studies with low adjustment (RR ratio 0.53; 95% CI 0.29-0.97; P = 0.039). CONCLUSIONS: There may be sex-related differences in the risks of MACE, any fracture, and hip fracture in patients with SH.

Diabetic ferroptosis plays an important role in triggering on inflammation in diabetic wound.

Impaired wound healing is a major complication of diabetes and involves sustained inflammation and oxidative stress at the wound site. Here, we investigated the potential involvement of ferroptosis, a newly discovered form of cell death characterized by iron-dependent accumulation of lipid peroxides in the pathogenesis of diabetic wound healing. Fibroblasts and vascular endothelial cells exposed to high glucose concentrations in vitro contained elevated levels of reactive oxygen species (ROS), lipid peroxidation products, and ferroptosis-associated proteins and displayed reduced survival and migration. These effects of high glucose were all significantly reduced by treatment with the ferroptosis inhibitor ferrostatin-1 (Fer-1). Similarly, in a rat model of diabetes, direct application of Fer-1 to the wound site reduced the expression of oxidative stress and inflammation markers and accelerated wound healing via activation of the anti-inflammatory phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT) pathway. Our results implicate ferroptosis in wound healing and identify a potential new therapeutic target for difficult-to-treat diabetic wounds.NEW & NOTEWORTHY Ferroptosis-related characteristic changes were found in diabetic wound models. Inhibition of ferroptosis improved inflammatory infiltration of diabetic wounds. PI3K/AKT signal pathway was rescued by restraining of ferroptosis. Mitigation of ferroptosis in diabetic wound promoted the wound healing.

LINC00174 Facilitates Cell Proliferation, Cell Migration and Tumor Growth of Osteosarcoma via Regulating the TGF-ß/SMAD Signaling Pathway and Upregulating SSH2 Expression.

Osteosarcoma (OS), a frequent malignant tumor which mainly occurs in the bone. The roles of long noncoding RNAs (lncRNAs) have been revealed in cancers, including OS. LncRNA long intergenic non-protein coding RNA (LINC00174) has been validated as an oncogene in several cancers. However, the role of LINC00174 in OS has not been explored. In our research, loss-of-function assays were conducted to explore the function of LINC00174 in OS cells. Then, we explored the downstream pathway of LINC00174 in OS cells. Bioinformatics, RNA pull-down and RIP experiments investigated the downstream mechanism of LINC00174 in OS cells. Finally, in vivo assays clarified the effect of LINC00174 on tumorigenesis. We found that LINC00174 was upregulated in OS tissues and cells. LINC00174 knockdown repressed OS cell growth. Mechanistically, LINC00174 knockdown suppressed the TGF-ß/SMAD pathway. LINC00174 interacted with miR-378a-3p, and slingshot protein phosphatase 2 (SSH2) 3'UTR was targeted by miR-378a-3p in OS cells. Rescue assays showed that SSH2 upregulation or miR-378a-3p inhibition counteracted the inhibitory effect of LINC00174 depletion in OS cell growth. Additionally, LINC00174 depletion suppressed tumor growth in mice. In conclusion, LINC00174 promotes OS cellular malignancy and tumorigenesis via the miR-378a-3p/SSH2 axis and the TGF-ß/SMAD pathway, which might provide a novel insight for OS treatment.

Risk Factors and Imaging Mechanisms of Fatigue After Mild Ischemic Stroke: An Exploratory Study From a Single Chinese Center.

Objective: To explore the biochemical risk factors and imaging mechanisms of post fatigue after mild ischemic stroke among a Chinese population. Methods: Forty consecutive patients with mild ischemic stroke within onset of 14 ± 2 days were enrolled between March and June 2018. The clinical information, scale data, biomarkers in peripheral venous blood, and imaging data during hospitalization and follow-up period were collected. Results: Patient age (range 34-78) was positively correlated with the prevalence of fatigue (p = 0.009). Both blood norepinephrine and serotonin levels during hospitalization were negatively correlated to the prevalence of post-stroke fatigue (model 1 p = 0.009 and model 2 P = 0.043, respectively). Infarct of right cerebral hemisphere is positively correlated with the occurrence of fatigue after mild ischemic stroke (p = 0.020). Compared to non-fatigue patients, amplitude of low-frequency fluctuation (ALFF) was lower in several areas of brain in stroke patients with fatigue, including the right orbital inferior frontal, right inner orbital frontal, right frontal, right triangular frontal inferior, right anterior and lateral cingulate, and right medial frontal gyruses. Analysis of the difference in functional connectivity between the fatigue and non-fatigue groups found no cluster. Conclusions: Frontal lobe-related neural pathways may play an essential role in the regulation of fatigue after mild ischemic stroke. Abnormal neural circuits may reduce the levels of neurotransmitters such as serotonin and norepinephrine and lead to post-stroke fatigue.

Impact of Sleep Duration on Depression and Anxiety After Acute Ischemic Stroke.

Background: Abnormal sleep duration predicts depression and anxiety. We seek to evaluate the impact of sleep duration before stroke on the occurrence of depression and anxiety at 3 months after acute ischemic stroke (AIS). Methods: Nationally representative samples from the Third China National Stroke Registry were used to examine cognition and sleep impairment after AIS (CNSR-III-ICONS). Based on baseline sleep duration before onset of stroke as measured by using the Pittsburgh Sleep Quality Index (PSQI), 1,446 patients were divided into four groups: >7, 6-7, 5-6, and <5 h of sleep. Patients were followed up with the General Anxiety Disorder-7 (GAD-7) and Patient Health Questionnaire-9 (PHQ-9) for 3 months. Poststroke anxiety (PSA) was defined as GAD-7 of ≥5 and poststroke depression (PSD) as PHQ-9 of ≥5. The association of sleep duration with PSA and PSD was evaluated using multivariable logistic regression. Results: The incidences of PSA and PSD were 11.2 and 17.6% at 3 months, respectively. Compared to a sleep duration of >7 h, 5-6 h, and <5 h of sleep were identified as risk factors of PSA [odds ratio (OR), 1.95; 95% confidence interval (CI), 1.24-3.07; P < 0.01 and OR, 3.41; 95% CI, 1.94-6.04; P < 0.01) and PSD (OR, 1.47; 95% CI, 1.00-2.17; P = 0.04 and OR, 3.05; 95% CI, 1.85-5.02; P < 0.01), while 6-7 h of sleep was associated with neither PSA (OR, 1.09; 95% CI, 0.71-1.67; P = 0.68) nor PSD (OR, 0.92; 95% CI, 0.64-1.30; P = 0.64). In interaction analysis, the impact of sleep duration on PSA and PSD was not affected by gender (P = 0.68 and P = 0.29, respectively). Conclusions: Sleep duration of shorter than 6 h was predictive of anxiety and depression after ischemic stroke.

Profile Screening of Differentially Expressed lncRNAs of Circulating Leukocytes in Type 2 Diabetes Patients and Differences From Type 1 Diabetes.

Long noncoding RNAs (lncRNAs) have been reported to have multiple functions and can be used as markers of various diseases, including diabetes. This study was conducted to determine the lncRNA profile in leukocytes from patients with type 2 diabetes (T2D). Differential expression of lncRNAs in T2D and type 1 diabetes (T1D) was also examined. RNA sequencing was performed in a critically grouped sample of leukocytes from T2D patients and healthy persons. A total of 845 significantly differentially expressed lncRNAs were identified, with 260 downregulated and 585 upregulated lncRNAs in T2D. The analysis of functions of DE-lncRNA and constructed co-expression networks (CNC) showed that 21 lncRNAs and 117 mRNAs harbored more than 10 related genes in CNC. Fourteen of 21 lncRNAs were confirmed to be significantly differentially expressed was detected by qPCR between the T2D and control validation cohorts. We also identified a panel of 4 lncRNAs showing significant differences in expression between T1D and T2D. Collectively, hundreds of novel DE-lncRNAs we identified in leukocytes from T2D patients will aid in epigenetic mechanism studies. Fourteen confirmed DE-lncRNAs can be regarded as diagnostic markers or regulators of T2D, including 4 lncRNAs that chould distinguish T1D and T2D in clinical practice to avoid misdiagnosis.

A Genome-Wide Analysis of Long Noncoding RNAs in Circulating Leukocytes and Their Differential Expression in Type 1 Diabetes Patients.

Long noncoding RNAs (lncRNAs) regulate gene expression at different levels in various diseases, including type 1 diabetes (T1D). However, the expression of circulating lncRNAs in leukocytes in T1D has not been well documented. To identify differentially expressed lncRNAs between T1D patients and healthy controls, RNA sequencing was performed on samples of leukocytes collected from both healthy persons and T1D patients. The categories, enriched pathways, coexpression networks, and the characteristics of novel lncRNAs were analyzed to provide an extensive profile. qPCR was adopted to validate the differential expression of lncRNAs in the validation cohort. A total of 14,930 lncRNAs and 16,063 mRNAs were identified in the peripheral blood leukocyte of T1D patients. After optimization using an adjusted p value (threshold of <0.05), 393 circulating lncRNAs were identified, of which 69 were downregulated and 324 were upregulated in T1D patients. Gene Ontology analysis indicated that these lncRNAs and mRNAs were enriched in the immune system category. Further analysis showed that 61.28% of the novel lncRNAs were conserved in humans. A set of 12 lncRNAs were selected for qPCR validation, and 9 of 12 lncRNAs were confirmed to show significant differential expression between the T1D and control validation cohorts. Among the 9 confirmed lncRNAs, lncRNA MSTRG.128697 and lncRNA MSTRG.128958 were novel and human-specific; however, further validation is required. lncRNA MSTRG.63013 has orthologous sequences in the mouse genome and was identified as a key node for etiology and pathophysiology in animal studies, which will help understand the epigenetic mechanisms of T1D complications.

MiR-487a-3p suppresses the malignant development of pancreatic cancer by targeting SMAD7.

OBJECTIVE: To uncover the role of microRNA-487a-3p (miR-487a-3p) in influencing the malignant development of pancreatic cancer and the involvement of its downstream target SMAD7. METHODS: MiR-487a-3p level in 40 pancreatic cancer and paracancerous tissues was detected by quantitative real-time polymerase chain reaction (qRT-PCR). The relationship between miR-487a-3p level and clinical indicators in pancreatic cancer patients was analyzed. Regulatory effects of miR-487a-3p on biological phenotypes of pancreatic cancer cells were assessed. At last, the involvement of miR-487a-3p and its downstream target SMAD7 in pancreatic cancer was determined. RESULTS: MiR-487a-3p was lowly expressed in pancreatic cancer tissues. Pancreatic cancer patients expressing a low level of miR-487a-3p suffered high metastasis rate and poor prognosis. Overexpression of miR-487a-3p markedly attenuated proliferative and migratory capacities in pancreatic cancer cells. SMAD7 was the downstream target of miR-487a-3p, which was highly expressed in pancreatic cancer samples. Overexpression of SMAD7 reversed the regulatory effects of miR-487a-3p on pancreatic cancer cell phenotypes. CONCLUSIONS: MiR-487a-3p is downregulated in pancreatic cancer samples, which is linked to metastasis and prognosis in pancreatic cancer. It inhibits the malignant development of pancreatic cancer by negatively regulating SMAD7.

Hepatic insulin resistance induced by mitochondrial oxidative stress can be ameliorated by sphingosine 1-phosphate.

The bioactive lipid mediator sphingosine 1-phosphate (S1P) is considered to be involved in the development of insulin resistance (IR) via effects on oxidative stress; the mechanism however is not yet fully revealed. To this end, we investigated the role and mechanism of S1P on hepatic IR. We found that treatment of the normal human liver cell LO2 with 1000 nM insulin for 48 h reduced glucose uptake and increased serine phosphorylation of insulin receptor substrate-1, indicating a reduction in insulin receptor signaling. Moreover, the same concentration of insulin caused accumulation of reactive oxygen species (ROS) in the cytosol and mitochondria, and enhanced expression of the antioxidant transcription factor (Nrf2) and upregulated Nrf2 nuclear translocation. Using known inhibitors and donors of ROS (H2O2, ·O2-, ·OH), the results demonstrated the differential roles for the specific ROS in regulating IR in LO2 cells, with H2O2 having a more significant inhibitory role compared with ·O2- and ·OH. Cell treatment with S1P at 0.1-5.0 µM reversed the effects of high insulin concentrations on ROS generation, glucose uptake, and insulin signaling. H2O2 also reversed the beneficial effects of S1P in alleviating IR. These results show that H2O2 signaling plays a key determinant in hepatic IR induced by insulin. S1P can ameliorate hepatic IR by reducing mitochondrial ROS generation, and the possible anti-IR effect mechanism may be involved in H2O2 signaling.

[Impact of electroacupuncture on liver lipid metabolism and hepatic Sirt1 and PPARγ expression in abdominal obese rats].

OBJECTIVE: To observe the impact of electroacupuncture (EA) on liver lipid metabolism and expression of hepatic sirtuin 1(Sirt1) and peroxisome proliferator activated receptor γ(PPARγ) of abdominal obese rats induced by high-fat diet. METHODS: Eighteen male SD rats were divided into blank control, model and EA groups (n＝6 per group). The abdominal obesity model was established by feeding the rats with high-fat diet for 12 weeks. EA (2 Hz/15 Hz, 1.5 mA) was applied to bilateral "Daimai"(GB26) for 20 min every time, once every other day for 8 weeks. Rats of the model group were also restrained for 20 min. The body mass and abdominal circumference were measured every week, and the contents of serum cholesterol (TC), triglyceride (TG), alanine transaminase (ALT), aspartate aminotransferase (AST) were detected by using an automated biochemical analyzer. Histopathological changes of the liver tissues were observed under microscope after oil red "O" staining. The expression of hepatic Sirt1 and PPARγ mRNAs and proteins were detected using quantitative real time PCR and Western blot, separately. RESULTS: After modeling, the body weight and abdominal circumference, and serum TC, TG, ALT and AST contents, and expression of hepatic PPARγ mRNA and protein were significantly increased (P<0.001, P<0.01, P<0.05), and the expression levels of hepatic Sirt1 mRNA and protein obviously down-regulated (P<0.05, P<0.01) in the model group. Following EA intervention, the increased body weight and abdominal circumference, and serum TC, TG, ALT and AST contents, and hepatic PPARγ mRNA and protein expression were remarkably suppressed (P<0.05, P<0.01), and the decreased hepatic Sirt1 mRNA and protein were remarkably up-regulated (P<0.001，P<0.05). The lipid droplets in hepatocytes were reduced in the EA group relevant to the model group. CONCLUSION: EA intervention can significantly improve the liver lipid metabolism of abdominal obese rats, which is possibly related with its effect in up-regulating the expression of hepatic Sirt1 mRNA and protein, and in down-regulating the expression of hepatic PPARγ mRNA and protein.

Acupuncture Regulating Gut Microbiota in Abdominal Obese Rats Induced by High-Fat Diet.

OBJECTIVE: To investigate the effects of acupuncture on metabolic health and gut microbiota dysbiosis in diet-induced abdominal obese model. MATERIALS AND METHODS: Male Sprague-Dawley rats were randomly distributed into normal chow diet (NCD) group and high-fat diet (HFD) group. After 12 weeks of HFD feeding, an abdominal obese rat model was established. The abdominal obese rats were further assigned to acupuncture group (n=7) and nontreated HFD group (n=7). Acupuncture was applied to bilateral GB 26 of rats for 8 weeks. Subsequently, the body weight, waist circumference (WC), visceral fat mass, and liver weight were measured weekly in all rats. Metabolic parameters such as total cholesterol, triglyceride, alanine aminotransferase, aspartate transaminase, and blood glucose were measured by an automatic biochemical analyzer. The serum levels of insulin (INS) were determined using Rat INS ELISA Kit. Analysis of gut microbiota was carried out by 16S rRNA gene sequencing. RESULTS: Acupuncture decreased the body weight, WC, and visceral adipose tissues of HFD-induced abdominal obese rats. In addition, insulin sensitivity, glucose homeostasis, and lipid metabolism were improved by this treatment. Furthermore, electroacupuncture effectively modified the composition of gut microbiota, mainly via decreasing Firmicutes/Bacteroidetes ratio and increasing Prevotella_9 abundance. CONCLUSIONS: Electroacupuncture can ameliorate abdominal obesity and prevent metabolic disorders in HFD-induced abdominal obese rats, via the modulation of gut microbiota.