Network analysis combined with experimental assessment to explore the therapeutic mechanisms of New Shenqi Pills formula targeting mitochondria on senile diabetes mellitus.

Background: The escalation of global population aging has accentuated the prominence of senile diabetes mellitus (SDM) as a consequential public health concern. Oxidative stress and chronic inflammatory cascades prevalent in individuals with senile diabetes significantly amplify disease progression and complication rates. Traditional Chinese Medicine (TCM) emerges as a pivotal player in enhancing blood sugar homeostasis and retarding complication onset in the clinical management of senile diabetes. Nonetheless, an evident research gap persists regarding the integration of TCM's renal tonification pharmacological mechanisms with experimental validation within the realm of senile diabetes therapeutics. Aims: The objective of this study was to investigate the mechanisms of action of New Shenqi Pills (SQP) in the treatment of SDM and make an experimental assessment. Methods: Network analysis is used to evaluate target pathways related to SQP and SDM. Mitochondrial-related genes were obtained from the MitoCarta3.0 database and intersected with the common target genes of the disease and drugs, then constructing a protein-protein interaction (PPI) network making use of the GeneMANIA database. Representative compounds in the SQP were quantitatively measured using high performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) to ensure quality control and quantitative analysis of the compounds. A type 2 diabetes mice (C57BL/6) model was used to investigate the pharmacodynamics of SQP. The glucose lowering efficacy of SQP was assessed through various metrics including body weight and fasting blood glucose (FBG). To elucidate the modulatory effects of SQP on pancreatic beta cell function, we measured oral glucose tolerance test (OGTT), insulin histochemical staining and tunel apoptosis detection, then assessed the insulin-mediated phosphoinositide 3-kinase (PI3K)/protein kinase A (Akt)/glycogen synthase kinase-3ß (GSK-3ß) pathway in diabetic mice via Western blotting. Additionally, we observe the structural changes of the nucleus, cytoplasmic granules and mitochondria of pancreatic islet ß cells. Results: In this investigation, we identified a total of 1876 genes associated with senile diabetes, 278 targets of SQP, and 166 overlapping target genes, primarily enriched in pathways pertinent to oxidative stress response, peptide response, and oxygen level modulation. Moreover, an intersection analysis involving 1,136 human mitochondrial genes and comorbidity targets yielded 15 mitochondria-related therapeutic targets. Quality control assessments and quantitative analyses of SQP revealed the predominant presence of five compounds with elevated concentrations: Catalpol, Cinnamon Aldehyde, Rehmanthin D, Trigonelline, and Paeonol Phenol. Vivo experiments demonstrated notable findings. Relative to the control group, mice in the model group exhibited significant increases in body weight and fasting blood glucose levels, alongside decreased insulin secretion and heightened islet cell apoptosis. Moreover, ß-cells nuclear condensation and mitochondrial cristae disappearance were observed, accompanied by reduced expression levels of p-GSK-3ß protein in islet cells (p < 0.05 or p < 0.01). Conversely, treatment groups administered SQP and Rg displayed augmented expressions of the aforementioned protein markers (p < 0.05 or p < 0.01), alongside preserved mitochondrial cristae structure in islet ß cells. Conclusion: Our findings suggest that SQP can ameliorate diabetes by reducing islet cell apoptosis and resist oxidative stress. These insulin-mediated PI3K/AKT/GSK-3ß pathway plays an important regulatory role in this process.

Eco-efficiency evaluation model: a case study of the Yangtze River Economic Belt.

After the concept of ecological efficiency (eco-efficiency) was put forward and constantly supplemented, it generally refers to the maximization of economic benefits with minimum energy consumption and environmental damage. In a new eco-efficiency model proposed by this paper, the input indexes take into account the consumption of capital, human, resources and energy, and the environmental load caused by them. The output indexes take into account GDP, income, and tax revenue. An optimal weighted cross-evaluation efficiency (OWCE) model based on data standardization is proposed, by improving the traditional data envelopment models of CCR and BCC. The OWCE model not only objectively weights but also unifies the comparison scale, and facilitates the establishment of the super-efficiency decomposition model, which is conducive to further exploring the reasons for the difference of eco-efficiency in various regions. Empirically, the eco-efficiencies of 11 provinces (municipalities) along the Yangtze River Economic Belt (YREB) were analyzed based on the data from 2008 to 2019. The results show that there has been a serious imbalance in the 11 provinces, showing a trend of high in the east and low in the west, although the eco-efficiency has been improving continuously in the past 10 years. Shanghai, Zhejiang, and Jiangsu, which are located in the traditional Yangtze River lower delta region, are the top in terms of eco-efficiency, among which Shanghai ranks the first place with absolute advantage, and also is far ahead in sub-efficiencies of basic input, energy consumption, capital and human input, and environmental cost. Geographical location, especially whether it is close to the ocean, and the length of river flow have a certain positive impact on eco-efficiency. Through in-depth analysis, high-energy consumption, high pollution, and low economic output are the main reasons for low eco-efficiency in the middle and upper reaches of the Yangtze River.

Educational Attainment and Ischemic Stroke: A Mendelian Randomization Study.

Observational studies have evaluated the potential association of socioeconomic factors such as higher education with the risk of stroke but reported controversial findings. The objective of our study was to evaluate the potential causal association between higher education and the risk of stroke. Here, we performed a Mendelian randomization analysis to evaluate the potential association of educational attainment with ischemic stroke (IS) using large-scale GWAS datasets from the Social Science Genetic Association Consortium (SSGAC, 293,723 individuals), UK Biobank (111,349 individuals), and METASTROKE consortium (74,393 individuals). We selected three Mendelian randomization methods including inverse-variance-weighted meta-analysis (IVW), weighted median regression, and MR-Egger regression. IVW showed that each additional 3.6-year increase in years of schooling was significantly associated with a reduced IS risk (OR = 0.54, 95% CI: 0.41-0.71, and p = 1.16 × 10-5). Importantly, the estimates from weighted median (OR = 0.49, 95% CI: 0.33-0.73, and p = 1.00 × 10-3) and MR-Egger estimate (OR = 0.18, 95% CI: 0.06-0.60, and p = 5.00 × 10-3) were consistent with the IVW estimate in terms of direction and magnitude. In summary, we provide genetic evidence that high education could reduce IS risk.

The impact of environmental regulation on employment: an empirical study of China's Two Control Zone policy.

Environmental regulations affect employment through productivity output and factor substitution. This paper employs a difference-in-differences (DID) method to investigate the effect of China's Two Control Zones (TCZ) policy on the urban employment in 287 cities from 1994 to 2009. We apply the DID method to two time points: 1998 for policy issuance and 2000 for the policy implementation. From the results of analyses on full-sample cities, the TCZ policy did not contribute to increasing total urban employment. Moreover, a negative impact on employment resulted from sulfur dioxide and acid rain controls in secondary and tertiary industries, respectively. In the acid rain control zone, the TCZ policy increased the average wage of urban workers. Negative effects on employment were observed in larger cities. The policy triggered labor migration from larger to smaller cities, resulting in significant increases in primary and tertiary industry employment in smaller cities, although the effects on mid-size cities were insignificant. This study provides important empirical evidence and insight into the impact of the TCZ policy on urban employment.

A review of the use of bromelain in cardiovascular diseases.

BACKGROUND: In 2004 an estimated 17.1 million people died from cardiovascular diseases (CVDs) worldwide, representing 29% of all global deaths. According to the American Heart Association, heart disease and stroke are the main cause of death and disability among people with type 2 diabetes. Additional safe and effective approaches are needed for the prevention and management of CVDs which may include nutritional supplements. OBJECTIVE: To identify the potential of bromelain (a food supplement) on the risk factors associated with CVDs. SEARCH STRATEGY: An electronic and manual search was conducted during November 2009 to March 2010. The databases searched included: Ovid MEDLINE; All EBM Reviews-Cochrane Database of Systematic Reviews (Cochrane DSR), American College of Physicians (ACP) Journal Club, Database of Abstracts of Reviews of Effects (DARE), Cochrane Central Register of Controlled Trials (CCTR), Cochrane Methodology Register (CMR), Health Technology Assessment (HTA) and National Health Service Economic Evaluation Database (NHSEED); Allied and Complementary Medicine (AMED); British Nursing Index and Archive; EMBASE; Health Management Information Consortium (HMIC); Science Direct and Electronic Thesis Online Services (ETHOS). Only papers in the English language were included. INCLUSION CRITERIA: Randomised controlled trials (RCTs), human studies, animal studies and experimental studies related to bromelain for CVDs. DATA EXTRACTION AND ANALYSIS: The quality assessment of all the selected studies was conducted by the authors. Data from 3 animal trials and 3 human trials were included in the review. Data collected included: type of trial, drug dosage, duration, outcome measures, characteristics of bromelain used, significance of results and conclusion. RESULTS: Out of 223 papers retrieved, 6 papers met the inclusion criteria and could be included in the review. These comprised of 3 animal and 3 human trials, each of which investigated the use of bromelain for CVDs. Results suggested that bromelain could be used for treating acute thrombophlebitis, as it decreases aggregation of blood platelets, has a cardio-protective effect, ameliorates rejection-induced arterial wall remodelling, prevents thrombin-induced human platelet aggregation as well as reduces thrombus formation. CONCLUSION: No substantive study of bromelain and clinical CVDs has been carried out in human populations. Only a few studies on bromelain and CVDs were published from 1948 to 2010. This may be an area worthy to be explored in future CVDs research.