CircATF6 inhibits hepatocellular carcinoma progression by suppressing calreticulin-mediated Wnt/ß-catenin signaling pathway.

Circular RNAs (circRNAs) are covalently closed, single-stranded RNAs that play critical roles in various biological processes and diseases, including cancers. However, the functions and mechanisms of circRNAs in hepatocellular carcinoma (HCC) need further clarification. Here, we identified and confirmed that circATF6 is downregulated in HCC tissues and negatively associated with the overall survival of HCC patients. Ectopic overexpression of circATF6 inhibits malignant phenotypes of HCC cells in vitro and in vivo, while knockdown of circATF6 had opposite effects. Mechanistically, we found that circATF6 bound to calreticulin (CALR) protein and acted as a scaffold to enhance the interaction of CALR with calpain2 (CAPN2), which promoted the degradation of CALR by its enzymatic activity. Moreover, we found that circATF6 inhibited HCC cells by suppressing CALR-mediated wnt/ß-catenin signaling pathway. Taken together, our findings suggest that circATF6 is a potential prognostic biomarker and therapeutic target for HCC.

Lipoprotein (a)-Related Inflammatory Imbalance: A Novel Horizon for the Development of Atherosclerosis.

PURPOSE OF REVIEW: The primary objective of this review is to explore the pathophysiological roles and clinical implications of lipoprotein(a) [Lp(a)] in the context of atherosclerotic cardiovascular disease (ASCVD). We seek to understand how Lp(a) contributes to inflammation and arteriosclerosis, aiming to provide new insights into the mechanisms of ASCVD progression. RECENT FINDINGS: Recent research highlights Lp(a) as an independent risk factor for ASCVD. Studies show that Lp(a) not only promotes the inflammatory processes but also interacts with various cellular components, leading to endothelial dysfunction and smooth muscle cell proliferation. The dual role of Lp(a) in both instigating and, under certain conditions, mitigating inflammation is particularly noteworthy. This review finds that Lp(a) plays a complex role in the development of ASCVD through its involvement in inflammatory pathways. The interplay between Lp(a) levels and inflammatory responses highlights its potential as a target for therapeutic intervention. These insights could pave the way for novel approaches in managing and preventing ASCVD, urging further investigation into Lp(a) as a therapeutic target.

Sedentary behaviour among elderly patients after total knee arthroplasty and its influencing factors.

To understand the status of sedentary behaviour in elderly patients after total knee arthroplasty and analyse its influencing factors so as to provide a reference for developing targeted interventions. Conveniently selected elderly patients undergoing total knee arthroplasty (> 6 months) in a tertiary hospital in Jiangsu Province were investigated using a general information questionnaire, the Charlson Comorbidity Index, patients' self-reported sedentary behaviour information, the WOMAC Score, The Groningen Orthopaedic Social Support Scale, and Lee's Fatigue. The median daily sedentary time was 5.5 h (4.5 h, 6.625 h) in 166 elderly patients after total knee arthroplasty, of whom 82 (49.40%) showed sedentary behaviour (≥ 6 h per day). Logistic regression analysis showed that being retired/unemployed (OR = 8.550, 95% CI 1.732-42.207, P = 0.0084), having a CCI score ≥ 3 (OR = 9.018, 95% CI 1.288-63.119, P < 0.0001), having high WOMAC scores (OR = 1.783, 95% CI 1.419-2.238, P < 0.0001), having a high social support score (OR = 1.155, 95% CI 1.031-1.294, P = 0.0130), and having a fatigue score ≥ 5 (OR = 4.848, 95% CI 1.084-21.682, P = 0.0389) made patients more likely to be sedentary. The sedentary time of elderly patients after total knee arthroplasty is long, and sedentary behaviour is common among them. Healthcare professionals should develop targeted sedentary behaviour interventions based on the influencing factors of sedentary behaviour in order to reduce the occurrence of sedentary behaviour in elderly patients after total knee arthroplasty.

Effectiveness and safety of tripterygium wilfordii poly-glycosides on glomerulonephritis: a systematic review and meta-analysis.

Treatment of glomerulonephritis presents several challenges, including limited therapeutic options, high costs, and potential adverse reactions. As a recognized Chinese patent medicine, Tripterygium wilfordii poly-glycosides (TWP) have shown promising benefits in managing autoimmune diseases. To evaluate clinical effectiveness and safety of TWP in treating glomerulonephritis, we systematically searched PubMed, Cochrane Library, Web of Science, and Embase databases for controlled studies published up to 12 July 2023. We employed weighted mean difference and relative risk to analyze continuous and dichotomous outcomes. This meta-analysis included 16 studies that included primary membranous nephropathy (PMN), type 2 diabetic kidney disease (DKD), and Henoch-Schönlein purpura nephritis (HSPN). Analysis revealed that additional TWP administration improved patients' outcomes and total remission rates, reduced 24-h urine protein (24hUP) and decreased relapse events. The pooled results demonstrated the non-inferiority of TWP to glucocorticoids in achieving total remission, reducing 24hUP, and converting the phospholipase A2 receptor (PLA2R) status to negative. For DKD patients, TWP effectively reduced 24hUP levels, although it did not significantly improve the estimated glomerular filtration rate (eGFR). Compared to valsartan, TWP showed comparable improvements in 24hUP and eGFR levels. In severe cases of HSPN in children, significant clinical remission and a reduction in 24hUP levels were observed with the addition of TWP treatment. TWP did not significantly increase the incidence of adverse reactions. Therefore, TWP could offer therapeutic benefits to patients with PMN, DKD, and severe HSPN, with a minimal increase in the risk of side effects.

Yak meat content in feed and its impact on the growth of rats.

To evaluate the effects of varying proportions of yak meat in feed on the growth of rats and provide a theoretical basis for selecting the optimal feed proportion suitable for rats. This study was designed as a one-variable experiment. Fifty male rats were divided into five groups. The ratios of yak meat to basal feed of rats in four dietary treatment groups were 2:8, 4:6, 6:4, and 8:2, respectively, while those in the control group were only provided a basal diet. In the feeding experiment, the body weights of the rats were recorded on Day 0 and subsequently in the first, second, third, and fourth weeks, along with quantities of feed intake. The body and tail lengths, as well as the waist circumference of the rats, were measured, and blood samples were collected in the fourth week for routine blood and biochemistry investigations. The rats in the 4:6 feed group had the best body condition. They had normal body and tail lengths, smaller waist circumferences, good posture, and were in better overall health than rats in the other groups. The results indicate that the 4:6 diet was optimal for enhancing rats' growth performance compared to the other diets.

Which SDM Model, CLIMEX vs. MaxEnt, Best Forecasts Aeolesthes sarta Distribution at a Global Scale under Climate Change Scenarios?

A precise evaluation of the risk of establishing insect pests is essential for national plant protection organizations. This accuracy is crucial in negotiating international trade agreements for forestry-related commodities, which have the potential to carry pests and lead to unintended introductions in the importing countries. In our study, we employed both mechanistic and correlative niche models to assess and map the global patterns of potential establishment for Aeolesthes sarta under current and future climates. This insect is a significant pest affecting tree species of the genus Populus, Salix, Acer, Malus, Juglans, and other hardwood trees. Notably, it is also categorized as a quarantine pest in countries where it is not currently present. The mechanistic model, CLIMEX, was calibrated using species-specific physiological tolerance thresholds, providing a detailed understanding of the environmental factors influencing the species. In contrast, the correlative model, maximum entropy (MaxEnt), utilized species occurrences and spatial climatic data, offering insights into the species' distribution based on observed data and environmental conditions. The projected potential distribution from CLIMEX and MaxEnt models aligns well with the currently known distribution of A. sarta. CLIMEX predicts a broader global distribution than MaxEnt, indicating that most central and southern hemispheres are suitable for its distribution, excluding the extreme northern hemisphere, central African countries, and the northern part of Australia. Both models accurately predict the known distribution of A. sarta in the Asian continent, and their projections suggest a slight overall increase in the global distribution range of A. sarta with future changes in climate temperature, majorly concentrating in the central and northern hemispheres. Furthermore, the models anticipate suitable conditions in Europe and North America, where A. sarta currently does not occur but where its preferred host species, Populus alba, is present. The main environmental variables associated with the distribution of A. sarta at a global level were the average annual temperature and precipitation rate. The predictive models developed in this study offer insights into the global risk of A. sarta establishment and can be valuable for monitoring potential pest introductions in different countries. Additionally, policymakers and trade negotiators can utilize these models to make science-based decisions regarding pest management and international trade agreements.

Design, Synthesis, and Biological Evaluation of Novel Purine Derivatives as Herbicide Safeners.

Mesosulfuron-methyl, an inhibitor of acetolactate synthase (ALS), has been extensively used in wheats. However, it can damage wheat (Triticum aestivum) and even lead to crop death. Herbicide safeners selectively shield crops from such damage without compromising weed control. To mitigate the phytotoxicity of mesosulfuron-methyl in crops, several purine derivatives were developed based on active substructure splicing. The synthesized title compounds underwent thorough characterization using infrared spectroscopy, 1H nuclear magnetic resonance (1H NMR), 13C nuclear magnetic resonance (13C NMR), and high-resolution mass spectrometry. We evaluated chlorophyll and glutathione contents as well as various enzyme activities to evaluate the safer activity of these compounds. Compounds III-3 and III-7 exhibited superior activity compared with the safener mefenpyr-diethyl. Molecular structure analysis, along with predictions of absorption, distribution, metabolism, excretion, and toxicity, indicated that compound III-7 shared pharmacokinetic traits with the commercial safener mefenpyr-diethyl. Molecular docking simulations revealed that compound III-7 competitively bound to the ALS active site with mesosulfuron-methyl, elucidating the protective mechanism of the safeners. Overall, this study highlights purine derivatives as potential candidates for novel safener development.

Prohibitin 1 inhibits cell proliferation and induces apoptosis via the p53-mediated mitochondrial pathway in vitro.

BACKGROUND: Prohibitin 1 (PHB1) has been identified as an antiproliferative protein that is highly conserved and ubiquitously expressed, and it participates in a variety of essential cellular functions, including apoptosis, cell cycle regulation, proliferation, and survival. Emerging evidence indicates that PHB1 may play an important role in the progression of hepatocellular carcinoma (HCC). However, the role of PHB1 in HCC is controversial. AIM: To investigate the effects of PHB1 on the proliferation and apoptosis of human HCC cells and the relevant mechanisms in vitro. METHODS: HCC patients and healthy individuals were enrolled in this study according to the inclusion and exclusion criteria; then, PHB1 levels in the sera and liver tissues of these participates were determined using ELISA, RT-PCR, and immunohistochemistry. Human HepG2 and SMMC-7721 cells were transfected with the pEGFP-PHB1 plasmid and PHB1-specific shRNA (shRNA-PHB1) for 24-72 h. Cell proliferation was analysed with an MTT assay. Cell cycle progression and apoptosis were analysed using flow cytometry (FACS). The mRNA and protein expression levels of the cell cycle-related molecules p21, Cyclin A2, Cyclin E1, and CDK2 and the cell apoptosis-related molecules cytochrome C (Cyt C), p53, Bcl-2, Bax, caspase 3, and caspase 9 were measured by real-time PCR and Western blot, respectively. RESULTS: Decreased levels of PHB1 were found in the sera and liver tissues of HCC patients compared to those of healthy individuals, and decreased PHB1 was positively correlated with low differentiation, TNM stage III-IV, and alpha-fetoprotein ≥ 400 µg/L. Overexpression of PHB1 significantly inhibited human HCC cell proliferation in a time-dependent manner. FACS revealed that the overexpression of PHB1 arrested HCC cells in the G0/G1 phase of the cell cycle and induced apoptosis. The proportion of cells in the G0/G1 phase was significantly increased and the proportion of cells in the S phase was decreased in HepG2 cells that were transfected with pEGFP-PHB1 compared with untreated control and empty vector-transfected cells. The percentage of apoptotic HepG2 cells that were transfected with pEGFP-PHB1 was 15.41% ± 1.06%, which was significantly greater than that of apoptotic control cells (3.65% ± 0.85%, P < 0.01) and empty vector-transfected cells (4.21% ± 0.52%, P < 0.01). Similar results were obtained with SMMC-7721 cells. Furthermore, the mRNA and protein expression levels of p53, p21, Bax, caspase 3, and caspase 9 were increased while the mRNA and protein expression levels of Cyclin A2, Cyclin E1, CDK2, and Bcl-2 were decreased when PHB1 was overexpressed in human HCC cells. However, when PHB1 was upregulated in human HCC cells, Cyt C expression levels were increased in the cytosol and decreased in the mitochondria, which indicated that Cyt C had been released into the cytosol. Conversely, these effects were reversed when PHB1 was knocked down. CONCLUSION: PHB1 inhibits human HCC cell viability by arresting the cell cycle and inducing cell apoptosis via activation of the p53-mediated mitochondrial pathway.

A T cell-based SARS-CoV-2 spike protein vaccine provides protection without antibodies.

SARS-CoV-2 spike-based vaccines are used to control the COVID-19 pandemic. However, emerging variants have become resistant to antibody neutralization and further mutations may lead to full resistance. We tested whether T cells alone could provide protection without antibodies. We designed a T cell-based vaccine in which SARS-CoV-2 spike sequences were rearranged and attached to ubiquitin. Immunization of mice with the vaccine induced no specific antibodies, but strong specific T cell responses. We challenged mice with SARS-CoV-2 wild-type strain or an Omicron variant after the immunization and monitored survival or viral titers in the lungs. The mice were significantly protected against death and weight loss caused by the SARS-CoV-2 wild-type strain, and the viral titers in the lungs of mice challenged with the SARS-CoV-2 wild-type strain or the Omicron variant were significantly reduced. Importantly, depletion of CD4+ or CD8+ T cells led to significant loss of the protection. Our analyses of spike protein sequences of the variants indicated that fewer than one-third presented by dominant HLA alleles were mutated and that most of the mutated epitopes were in the subunit 1 region. As the subunit 2 region is conservative, the vaccines targeting spike protein are expected to protect against future variants due to the T cell responses.

Application of hyperbaric oxygen therapy in diabetic foot ulcers: A meta-analysis.

Hyperbaric oxygen therapy (HBOT) has been used in patients with diabetic foot ulcers (DFU) for many years, but its clinical efficacy is still controversial. Therefore, this study explored the efficacy of HBOT applied to DFU by means of meta-analysis. PubMed, Cochrane Library, Embase, CNKI and Wanfang databases were searched, from database inception to October 2023, and published randomised controlled trials (RCTs) of HBOT in DFU were collected. Two investigators independently screened the collected literature, extracted relevant data and assessed the quality of the literature. Review Manager 5.4 software was applied for data analysis. Twenty-nine RCTs with 1764 patients were included. According to the combined results, when compared with conventional treatment, HBOT significantly increased the complete healing rate of DFUs (46.76% vs. 24.46%, odds ratio [OR]: 2.83, 95% CI: 2.29-3.51, p < 0.00001) and decreased the amputation rate (26.03% vs. 45.00%, OR: 0.41, 95% CI: 0.18-0.95, p = 0.04), but the incidence of adverse events was significantly higher in patients (17.37% vs. 8.27%, OR: 2.49, 95% CI: 1.35-4.57, p = 0.003), whereas there was no significant difference in the mortality (6.96% vs. 12.71%, OR: 0.52, 95% CI: 0.21-1.28, p = 0.16). Our results suggest that HBOT is effective in increasing the complete healing rate and decreasing the amputation rate in patients with DFUs, but increases the incidence of adverse events, while it has no significant effect on mortality.

In silico designed novel multi-epitope mRNA vaccines against Brucella by targeting extracellular protein BtuB and LptD.

Brucella, a gram-negative intracellular bacterium, causing Brucellosis, a zoonotic disease with a range of clinical manifestations, from asymptomatic to fever, fatigue, loss of appetite, joint and muscle pain, and back pain, severe patients have developed serious diseases affecting various organs. The mRNA vaccine is an innovative type of vaccine that is anticipated to supplant traditional vaccines. It is widely utilized for preventing viral infections and for tumor immunotherapy. However, research regarding its effectiveness in preventing bacterial infections is limited. In this study, we analyzed the epitopes of two proteins of brucella, the TonB-dependent outer membrane receptor BtuB and the LPS assembly protein LptD, which is involved in nutrient transport and LPS synthesis in Brucella. In order to effectively stimulate cellular and humoral immunity, we utilize a range of immunoinformatics tools such as VaxiJen, AllergenFPv.1.0 and SignalP 5.0 to design proteins. Finally, five cytotoxic T lymphocyte (CTL) cell epitopes, ten helper T lymphocyte (HTL) cell epitopes, and eight B cell epitopes were selected to construct the vaccine. Computer simulations are also used to verify the immune response of the vaccine. The codon optimization, in silico cloning showed that the vaccine can efficiently transcript and translate in E. coli. The secondary structure of mRNA vaccines and the secondary and tertiary structures of vaccine peptides were predicted and then docked with TLR-4. Finally, the stability of the developed vaccine was confirmed through molecular dynamics simulation. These analyses showed that the design the multi-epitope mRNA vaccine could potentially target extracellular protein of prevalent Brucella, which provided novel strategies for developing the vaccine.

Building a reference indicator model using co-kriging interpolation to determine the geographical origin of the flighted spongy moth complex in China.

Using stable isotopes to detect and analyze the geographical origin of insects represents an important traceability technology, which requires a rich isotope database. In this study, we representatively sampled the Chinese provinces where flighted spongy moth complex (FSMC) has been reported and, for the first time, used co-kriging interpolation to predict the distribution patterns of FSMC δ13 C values in the main distribution areas. From 2020 to 2022, we set up 60 traps in 12 provinces and cities in China and collected 795 FSMCs. Then, 6 main climatic factors were obtained by multi-collinearity screening from 21 types of meteorological data collected at the sample plots, and a correlation analysis was carried out by combining longitude, latitude, and altitude data with the δ13 C values of FSMC. Next, we performed a co-kriging interpolation using the 2 climatic factors with the highest correlation (isothermality and altitude) and the δ13 C values of FSMC. A cross-validation was performed to systematically test 11 candidate models and select the best semi-variogram model ("Exponential"), which was then used to build a co-kriging interpolation model. The geographical distribution patterns of the FSMC δ13 C values obtained from the 2 interpolation models (i.e., interpolated with isothermality and altitude, respectively) were almost the same. Moreover, the δ13 C values varied significantly at the regional scale, showing regular changes in spatial distribution. Overall, the reference indicator map of the δ13 C values generated from stable isotopes can be used to greatly improve the efficiency of discrimination analyses on the geographical origin of FSMC.

TRIM29 modulates proteins involved in PTEN/AKT/mTOR and JAK2/STAT3 signaling pathway and suppresses the progression of hepatocellular carcinoma.

Tripartite motif-containing 29 (TRIM29), also known as the ataxia telangiectasia group D-complementing (ATDC) gene, has been reported to play an oncogenic or tumor suppressive role in developing different tumors. So far, its expression and biological functions in hepatocellular carcinoma (HCC) remain unclear. We investigated TRIM29 expression pattern in human HCC samples using quantitative RT-PCR and immunohistochemistry. Relationships between TRIM29 expression level, clinical prognostic indicators, overall survival (OS), and disease-free survival (DFS) were evaluated by Kaplan-Meier analysis and Cox proportional hazards model. A series of in vitro experiments and a xenograft tumor model were conducted to detect the functions of TRIM29 in HCC cells. RNA sequencing, western blotting, and immunochemical staining were performed to assess the molecular regulation of TRIM29 in HCC. We found that the mRNA and protein levels of TRIM29 were significantly reduced in HCC samples, compared with adjacent noncancerous tissues, and were negatively correlated with poor differentiation of HCC tissues. Survival analysis confirmed that lower TRIM29 expression significantly correlated with shorter OS and DFS of HCC patients. TRIM29 overexpression remarkably inhibited cell proliferation, migration, and EMT in HCC cells, whereas knockdown of TRIM29 reversed these effects. Moreover, deactivation of the PTEN/AKT/mTOR and JAK2/STAT3 pathways might be involved in the tumor suppressive role of TRIM29 in HCC. Our findings indicate that TRIM29 in HCC exerts its tumor suppressive effects through inhibition of the PTEN/AKT/mTOR and JAK2/STAT3 signaling pathways and may be used as a potential biomarker for survival in patients with HCC.

The role of the Notch signaling pathway in bacterial infectious diseases.

The Notch signaling pathway is the most crucial link in the normal operation and maintenance of physiological functions of mammalian life processes. Notch receptors interact with ligands and this leads to three cleavages and goes on to enter the nucleus to initiate the transcription of target genes. The Notch signaling pathway deeply participates in the differentiation and function of various cells, including immune cells. Recent studies indicate that the outcomes of Notch signaling are changeable and highly dependent on different bacterial infection. The Notch signaling pathway plays a different role in promoting and inhibiting bacterial infection. In this review, we focus on the latest research findings of the Notch signaling pathway in bacterial infectious diseases. The Notch signaling pathway is critically involved in a variety of development processes of immunosuppression of different APCs. The Notch signaling pathway leads to functional changes in epithelial cells to aggravate tissue damage. Specifically, we illustrate the regulatory mechanism of the Notch signaling pathway in various bacterial infections, such as Mycobacterium tuberculosis, Mycobacterium avium paratuberculosis, Mycobacterium leprae, Helicobacter pylori, Klebsiella pneumoniae, Bacillus subtilis, Staphylococcus aureus, Ehrlichia chaffeensis and sepsis. Collectively, this review will not only help beginners intuitively and systematically understand the Notch signaling pathway in bacterial infectious diseases but also help experts to generate fresh insight in this field.

Impact of baseline and trajectory of the atherogenic index of plasma on incident diabetic kidney disease and retinopathy in participants with type 2 diabetes: a longitudinal cohort study.

BACKGROUND: Some studies have assessed the predictive role of the atherogenic index of plasma (AIP) for macrovascular diseases. This prospective investigation aimed to elucidate whether AIP is associated with diabetic kidney disease (DKD) and diabetic retinopathy (DR) incidence. METHODS: The data were extracted from 4831 participants, of whom 2943 and 3360 participants with type 2 diabetes (T2D) were included in the DKD and DR follow-up analyses, respectively. Cox regression models were performed to test the relationships of AIP value at baseline with the risk of incident DKD and DR. Group-based trajectory modelling was utilized to discern AIP trajectories during the follow-up period. Subsequently, logistic regressions were applied to ascertain the influence of AIP trajectories on the incidence of DKD and DR. RESULTS: During the follow-up period, 709 (24.1%) and 193 (5.7%) participants developed DKD and DR, respectively. The median (interquartile range) follow-up time was 24.2 (26.3) months for DKD and 25.7 (27.0) months for DR. According to the multivariate Cox regression models, baseline AIP was positively and linearly related to the occurrence of DKD, with a hazard ratio of 1.75 (95% confidence interval [CI] 1.36-2.26). Three distinct trajectories of AIP were identified throughout the follow-up time: Low (31.4%), Median (50.2%), and High (18.3%). Compared to participants with the Low AIP trajectory, those with High and Median AIP trajectories presented 117% (95% CI: 1.62-2.91) and 84% (95% CI 1.46-2.32) greater odds of developing DKD, respectively. However, neither baseline levels nor trajectories of AIP were shown to be related to DR after adjusting for confounding factors. CONCLUSIONS: Baseline levels and trajectories of AIP were independently related to elevated DKD risk, indicating that AIP could be used as a predictor for identifying T2D participants at higher risk of DKD. No association between AIP and DR was detected.

Two somatic mutations in the androgen receptor N-terminal domain are oncogenic drivers in hepatocellular carcinoma.

The androgen receptor (AR) plays an important role in male-dominant hepatocellular carcinoma, and specific acquired somatic mutations of AR have been observed in HCC patients. Our previous research have established the role of AR wild type as one of the key oncogenes in hepatocarcinogenesis. However, the role of hepatic acquired somatic mutations of AR remains unknown. In this study, we identify two crucial acquired somatic mutations, Q62L and E81Q, situated close to the N-terminal activation function domain-1 of AR. These mutations lead to constitutive activation of AR, both independently and synergistically with androgens, making them potent driver oncogene mutations. Mechanistically, these N-terminal AR somatic mutations enhance de novo lipogenesis by activating sterol regulatory element-binding protein-1 and promote glycogen accumulation through glycogen phosphorylase, brain form, thereby disrupting the AMPK pathway and contributing to tumorigenesis. Moreover, the AR mutations show sensitivity to the AMPK activator A769662. Overall, this study establishes the role of these N- terminal hepatic mutations of AR as highly malignant oncogenic drivers in hepatocarcinogenesis and highlights their potential as therapeutic targets for patients harboring these somatic mutations.

The effects of economic status on metabolic control in type 2 diabetes mellitus at 10 metabolic management centers in China.

OBJECTIVE: This study investigated the association of economic status with metabolic index control in type 2 diabetes mellitus (T2DM) patients. METHODS: In total, 37 454 T2DM patients from 10 National Metabolic Management Centers in China were recruited and categorized into two groups: a high-gross domestic product (GDP) group (n = 23 993) and a low-GDP group (n = 13 461). Sociodemographic characteristics, medical histories, and lifestyle factors were recorded. Logistic regression and interaction analysis were performed to evaluate the association of economic status and healthy lifestyle with metabolic control. RESULTS: Compared to the low-GDP group, there were fewer patients with glycated hemoglobin (HbA1c) levels ≥7% in the high-GDP group. Fewer patients with a high GDP had an abnormal metabolic state (HbA1c ≥ 7%, blood pressure [BP] ≥130/80 mm Hg, total cholesterol [TCH] ≥4.5 mmol/L or body mass index [BMI] ≥24 kg/m2 ). The risks of developing HbA1c ≥ 7% (odds ratios [OR] = 0.545 [95% CI: 0.515-0.577], p < .001), BP ≥ 130/80 mm Hg (OR = 0.808 [95% CI: 0.770-0.849], p < .001), BMI ≥ 24 kg/m2 (OR = 0.840 [95% CI: 0.799-0.884], p < .001), and an abnormal metabolic state (OR = 0.533 [95% CI: 0.444-0.636], p < .001) were significantly lower in the high-GDP group even after adjustment for confounding factors. Younger participants; those with a family history of diabetes, normal weight, and a physical activity level up to standard; and those who did not drink alcohol in the high-GDP group were predisposed to better glycemic levels. CONCLUSIONS: T2DM patients in economically developed regions had better metabolic control, especially glycemic control. A healthy lifestyle had an additive effect on achieving glycemic goals, even among high-GDP patients.

HMOX1 Participates in Pre-Eclampsia by Regulating the Proliferation, Apoptosis, and Angiogenesis Modulation Potential of Mesenchymal Stem Cells via VEGF.

Mesenchymal stem cells (MSCs) are involved in the pathogenesis of pre-eclampsia (PE). Heme oxygenase (HMOX) protects against placental cytotoxic injuries associated with PE. Here, we aimed to clarify the roles of HMOX1 in MSC proliferation and apoptosis, trophoblast cell migration, and regulation of angiogenesis, and assess its involvement in the pathogenesis of PE. HMOX1 and vascular endothelial growth factor (VEGF) expression levels in decidual tissues and decidua-derived MSCs (dMSCs) of healthy pregnant women and patients with PE were evaluated via quantitative reverse transcription-polymerase chain reaction and western blotting. Moreover, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide, flow cytometry, and transwell assays were used to analyze the cell viability, apoptosis, and migration, respectively. The tube formation ability of human umbilical vein endothelial cells (HUVECs) was also evaluated. Compared to the healthy pregnant women, HMOX1 expression was upregulated in the decidual tissue and downregulated in the dMSCs of patients with PE. HMOX1 overexpression significantly increased dMSC proliferation, decreased cell apoptosis, and increased VEGF expression. Moreover, HMOX1-plasmid transfected dMSC culture supernatant promoted the migration of HTR-8/SVneo cells and improved angiogenesis by HUVECs. The opposite effects were observed in HMOX1-small interfering RNA-treated dMSCs cells. However, VEGF-siRNA reversed the effects of HMOX1-plasmid. HMOX1 is involved in the pathogenesis of PE by regulating the proliferation, apoptosis, and angiogenesis modulation potential of MSCs via VEGF, acting as a potential therapeutic target for PE.