ABSTRACT
BACKGROUND: The triglyceride glucose (TyG) index is a cutting-edge and highly effective marker of insulin resistance, a crucial factor in the development and exacerbation of diabetic kidney disease (DKD). To date, there has been limited research on how the triglyceride-glucose (TyG) index affects the outlook for patients suffering from DKD. METHODS: In this multicenter retrospective cohort study, the analysis recruited 2,203 DKD patients from the National Health and Nutrition Examination Survey (NHANES) dataset, which covers the US from 2001 to 2018. The research applied a Cox proportional hazards model with multiple variables to investigate the association of the TyG index with mortality outcomes. Restricted cubic splines (RCS) and methods for analyzing threshold effects were employed to identify possible non-linear relationships. RESULTS: Over nearly 19 years of follow-up, this study captured data on 753 all-cause and 231 cardiovascular disease-specific fatalities. Sophisticated statistical methods, including RCS and smoothing curve adjustments via penalized splines, helped identify distinctive patterns: The baseline TyG index was observed to have a U-shaped pattern related to overall mortality and an L-shape with cardiovascular diseases(CVD) mortality among individuals with DKD. Notably, TyG index below 9.15 for overall mortality and 9.27 for CVD mortality were linked to reduced death rates (HR = 0.65, 95% CI = 0.52-0.82 for all-cause; HR = 0.58, 95% CI = 0.43-0.83 for CVD). On the other hand, TyG index exceeding these benchmarks (greater than 9.15 for all-cause and 9.27 for CVD) correlated with increased all-cause mortality risks (HR = 1.21, 95% CI = 1.02-1.43) and showed a non-significant change in CVD mortality risks (HR = 1.07, 95% CI = 0.83-1.38). CONCLUSIONS: This study emphasizes the non-linear linkage involving the TyG index and death rates due to CVD and other factors in patients with DKD, demonstrating its effectiveness in estimating potential adverse events within this demographic.
Subject(s)
Blood Glucose , Cardiovascular Diseases , Diabetes Mellitus, Type 2 , Diabetic Nephropathies , Nutrition Surveys , Triglycerides , Humans , Triglycerides/blood , Diabetic Nephropathies/mortality , Diabetic Nephropathies/blood , Male , Female , Middle Aged , Retrospective Studies , Cardiovascular Diseases/mortality , Cardiovascular Diseases/blood , Diabetes Mellitus, Type 2/mortality , Diabetes Mellitus, Type 2/blood , Diabetes Mellitus, Type 2/complications , Blood Glucose/analysis , Aged , Proportional Hazards Models , Adult , Risk FactorsABSTRACT
Cardiomyopathies (CMs) are highly heterogeneous progressive heart diseases characterised by structural and functional abnormalities of the heart, whose intricate pathogenesis has resulted in a lack of effective treatment options. Mitsugumin 53 (MG53), also known as Tripartite motif protein 72 (TRIM72), is a tripartite motif family protein from the immuno-proteomic library expressed primarily in the heart and skeletal muscle. Recent studies have identified MG53 as a potential cardioprotective protein that may play a crucial role in CMs. Therefore, the objective of this review is to comprehensively examine the underlying mechanisms mediated by MG53 responsible for myocardial protection, elucidate the potential role of MG53 in various CMs as well as its dominant status in the diagnosis and prognosis of human myocardial injury, and evaluate the potential therapeutic value of recombinant human MG53 (rhMG53) in CMs. It is expected to yield novel perspectives regarding the clinical diagnosis and therapeutic treatment of CMs.
Subject(s)
Cardiomyopathies , Myocardium , Humans , Myocardium/metabolism , Muscle, Skeletal/metabolism , Cardiomyopathies/drug therapy , Cardiomyopathies/metabolism , Heart , Treatment OutcomeABSTRACT
Aims: Previous Mendelian randomization (MR) of obesity and diabetic nephropathy (DN) risk used small sample sizes or focused on a single adiposity metric. We explored the independent causal connection between obesity-related factors and DN risk using the most extensive GWAS summary data available, considering the distribution of adiposity across childhood and adulthood. Methods: To evaluate the overall effect of each obesity-related exposure on DN (Ncase = 3,676, Ncontrol = 283,456), a two-sample univariate MR (UVMR) analysis was performed. The independent causal influence of each obesity-related feature on DN was estimated using multivariable MR (MVMR) when accounting for confounding variables. It was also used to examine the independent effects of adult and pediatric obesity, adjusting for their interrelationships. We used data from genome-wide association studies, including overall general (body mass index, BMI) and abdominal obesity (waist-to-hip ratio with and without adjustment for BMI, i.e., WHR and WHRadjBMI), along with childhood obesity (childhood BMI). Results: UVMR revealed a significant association between adult BMI (OR=1.24, 95%CI=1.03-1.49, P=2.06×10-2) and pediatric BMI (OR=1.97, 95%CI=1.59-2.45, P=8.55×10-10) with DN risk. At the same time, adult WHR showed a marginally significant increase in DN (OR =1.27, 95%CI = 1.01-1.60, P=3.80×10-2). However, the outcomes were adverse when the influence of BMI was taken out of the WHR (WHRadjBMI). After adjusting for childhood BMI, the causal effects of adult BMI and adult abdominal obesity (WHR) on DN were significantly attenuated and became nonsignificant in MVMR models. In contrast, childhood BMI had a constant and robust independent effect on DN risk(adjusted for adult BMI: IVW, OR=1.90, 95% CI=1.60-2.25, P=2.03×10-13; LASSO, OR=1.91, 95% CI=1.65-2.21, P=3.80×10-18; adjusted for adult WHR: IVW, OR=1.80, 95% CI=1.40-2.31, P=4.20×10-6; LASSO, OR=1.90, 95% CI=1.56-2.32, P=2.76×10-10). Interpretation: Our comprehensive analysis illustrated the hazard effect of obesity-related exposures for DN. In addition, we showed that childhood obesity plays a separate function in influencing the risk of DN and that the adverse effects of adult obesity (adult BMI and adult WHR) can be substantially attributed to it. Thus, several obesity-related traits deserve more attention and may become a new target for the prevention and treatment of DN and warrant further clinical investigation, especially in childhood obesity.
Subject(s)
Diabetes Mellitus , Diabetic Nephropathies , Pediatric Obesity , Adult , Child , Humans , Adiposity/genetics , Diabetic Nephropathies/etiology , Diabetic Nephropathies/genetics , Genome-Wide Association Study , Mendelian Randomization Analysis , Obesity, Abdominal , Pediatric Obesity/complications , Pediatric Obesity/epidemiology , Pediatric Obesity/geneticsABSTRACT
Cardio-metabolic diseases, including a cluster of metabolic disorders and their secondary affections on cardiovascular physiology, are gradually brought to the forefront by researchers due to their high prevalence and mortality, as well as an unidentified pathogenesis. tRNA-derived small RNAs (tsRNAs), cleaved by several specific enzymes and once considered as some "metabolic junks" in the past, have been proved to possess numerous functions in human bodies. More interestingly, such a potential also seems to influence the progression of cardio-metabolic diseases to some extent. In this review, the biogenesis, classification and mechanisms of tsRNAs will be discussed based on some latest studies, and their relations with several cardio-metabolic diseases will be highlighted in sequence. Lastly, some future prospects, such as their clinical applications as biomarkers and therapeutic targets will also be mentioned, in order to provide researchers with a comprehensive understanding of the research status of tsRNAs as well as its association with cardio-metabolic diseases, thus presenting as a beacon to indicate directions for the next stage of study.
Subject(s)
Metabolic Diseases , RNA, Transfer , Humans , RNA, Transfer/genetics , RNA, Transfer/metabolism , RNA/genetics , Metabolic Diseases/geneticsABSTRACT
Propolis is a well-known natural antibacterial substance with various biological activities, such as anti-inflammatory and antioxidant activity. However, applications of propolis are limited due to its low water solubility. In this study, propolis microcapsules were developed with a core material of ethanol extract of propolis and shell materials of gum arabic and ß-cyclodextrin using a spray-drying technique. The optional processing formula, particle size distribution, morphology, dissolution property, and antibacterial activity of propolis microcapsules were determined. The results showed that the optional processing obtained an embedding rate of 90.99% propolis microcapsules with an average particle size of 445.66 ± 16.96 nm. The infrared spectrogram and thermogravimetric analyses showed that propolis was embedded in the shell materials. The propolis microcapsules were continuously released in water and fully released on the eighth day, and compared to propolis, the microcapsules exhibited weaker antibacterial activity. The minimum inhibitory concentrations (MICs) of propolis microcapsules against Escherichia coli and Staphylococcus aureus were 0.15 and 1.25 mg/mL, and their minimum bactericidal concentrations (MBCs) were 0.3 and 1.25 mg/mL, respectively. This water-soluble propolis microcapsule shows the potential for use as a sustained-release food additive, preservative, or drug.
ABSTRACT
Salmonella enterica serovar Typhimurium (S. Typhimurium) is a common food-borne pathogen that commonly causes gastroenteritis in humans and animals. Apis laboriosa honey (ALH) harvested in China has significant antibacterial activity against Staphylococcus aureus, Escherichia coli, and Bacillus subtilis. We hypothesize that ALH has antibacterial activity against S. Typhimurium. The physicochemical parameters, minimum inhibitory and bactericidal concentrations (MIC and MBC) and the possible mechanism were determined. The results showed that there were significantly different physicochemical parameters, including 73 phenolic compounds, among ALH samples harvested at different times and from different regions. Their antioxidant activity was affected by their components, especially total phenol and flavonoid contents (TPC, TFC), which had a high correlation with antioxidant activities except for the O2- assay. The MIC and MBC of ALH against S. Typhimurium were 20-30% and 25-40%, respectively, which were close to those of UMF5+ manuka honey. The proteomic experiment revealed the possible antibacterial mechanism of ALH1 at IC50 (2.97%, w/v), whose antioxidant activity reduced the bacterial reduction reaction and energy supply, mainly by inhibiting the citrate cycle (TCA cycle), amino acid metabolism pathways and enhancing the glycolysis pathway. The results provide a theoretical basis for the development of bacteriostatic agents and application of ALH.
ABSTRACT
Public service motivation (PSM) represents an individual's predisposition to respond to motives grounded primarily or uniquely in public institutions, and it is an individual characteristic that reflects the attributes of the public sector. The concept was first introduced by James Perry, who identified four-dimensions to measure PSM, namely, attraction to policy making, commitment to the public interest, compassion, and self-sacrifice. Public service motivation changes over time, and differences in culture and systems in different countries can lead to differences in the measurement dimensions of PSM. The dimensions of PSM measurement in Asian countries are different from those in Western countries, and whether the regional applicability and population applicability of PSM can be expanded is a question worth investigating. From a new perspective, this study takes Chinese college students as the research object, using one-on-one interviews based on grounded theory. Besides the four dimensions mentioned above, it was found that the two additional dimensions of a collectivist tendency and self-improvement were added, and the specific connotations of each dimension were changed somewhat. A collectivist tendency accords with the culture of East Asian countries, and self-improvement is our unique finding among college students. This proves that the motivation for public service can rise not only from altruism but also as a result of individuals seeking self-development and value realization.
Subject(s)
Motivation , Students , Humans , Grounded Theory , Qualitative Research , ChinaABSTRACT
The 24p3/neutrophil gelatinase-associated lipocalin (NGAL) protein plays an important protective role in acute kidney injury (AKI), but the exact mechanism remains unclear. Therefore, we have made a preliminary exploration of its mechanism. The experimental group was formed by constructing and transfecting 24P3 overexpressed plasmid into renal tubular epithelial cells. Western Bolt was used to detect NGAL expression. Cell proliferation was detected by CCK8 kit, cell death was detected by Hoechst 33342 and PI kit, mitochondrial morphology was observed under light microscope, reactive oxygen species (ROS) content was detected by fluorescence probe, and iron level and glutathione peroxidase 4 (GPX4) activity were detected by kit. Furthermore, the mechanism of NGAL action was further demonstrated by adding ferrostein-1 (Fer-1), an ferroptosis inhibitor, and erastin (containing DMSO),an ferroptosis inductor. We found that ferroptosis-related indicators were lower in the NGAL overexpression group than in the control group. At the same time, we found that NGAL alleviated ferroptosis induced by erastin and coordinated with Fer-1 to alleviate ferroptosis. In conclusion, NGAL inhibits ferroptosis in renal tubular epithelial cells, which may be associated with the progression of AKI and may provide a new therapeutic target for the transition from acute kidney injury to chronic kidney injury.
Subject(s)
Acute Kidney Injury , Ferroptosis , Lipocalin-2 , Acute Kidney Injury/chemically induced , Acute Kidney Injury/metabolism , Biomarkers/metabolism , Epithelial Cells/metabolism , Ferroptosis/genetics , Humans , Kidney/metabolism , Lipocalin-2/genetics , Lipocalin-2/metabolismABSTRACT
It is challenging to reduce the cadmium (Cd) and arsenic (As) contents of brown rice simultaneously due to their converse chemical behaviors in the paddy soil. Clay minerals, such as sepiolite (SEP), have significant advantages in remediating Cd-contaminated soil. Moreover, iron or manganese oxide loaded SEP can improve the As adsorption efficiency. Herein, ferric nitrate modified sepiolite (NIMS) and ironmanganese modified sepiolite (FMS) were prepared to study their effects on Cd and As accumulation in rice using pot experiments. The results showed that NIMS and FMS had a larger specific surface area than SEP. The application of SEP only decreased Cd content (by 45%), while NIMS and FMS treatments reduced both Cd (by 57% and 87%) and As (by 30% and 25%) contents in brown rice compared with the control. The X-ray photoelectron spectroscopy (XPS) analysis results indicated that MnO2 and MnOOHâ in FMS enhanced the adsorption and co-precipitation of Cd as well as the oxidation of As(III) to As(V). The NIMS, as well as the FMS application, increased soil pH, decreased the exchangeable Cd and non-specifically and specifically adsorbed As fractions in soil, and reduced the level of Cd in the pore water. Moreover, NIMS and FMS addition limited the transfer of As from the soil to the roots by enhancing its sequestration in the iron plaque. On the other hand, FMS treatment significantly promoted the uptake of Mn by rice (P < 0.05). The results suggested that both NIMS and FMS were promising materials for simultaneous reduction of Cd and As accumulation in rice. Notably, FMS had better performance in reducing the Cd content in rice than that of NIMS.