Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 603
Filter
1.
Article in English | MEDLINE | ID: mdl-38782546

ABSTRACT

BACKGROUND: Cardiovascular diseases (CVDs) are the leading cause of death in the USA, and high blood pressure is a major risk factor for CVD. Despite the overall declining rates of CVD mortality in the USA in recent years, marked disparities between racial and ethnic groups persist, with black adults having a higher mortality rate than white adults. We investigated the extent to which blood pressure mediated the black-white disparity in CVD mortality. METHODS: Data came from the Multi-Ethnic Study of Atherosclerosis, a diverse longitudinal cohort. We included 1325 black and 2256 white community-based adults aged 45-80 years free of clinical CVD at baseline and followed for 14 years. We used causal mediation analysis to estimate the effect of race on CVD mortality that was mediated through blood pressure. RESULTS: Black participants had a higher hazard of dying from CVD compared with white participants (adjusted hazard ratio (HR): 1.28 (95% CI 0.88, 1.88)), though estimates were imprecise. Systolic blood pressure mediated 27% (HR: 1.02, 95% CI 1.00, 1.06) and diastolic blood pressure mediated 55% (HR: 1.07, 95% CI 1.01, 1.10) of the racial disparities in CVD mortality between white and black participants. Mediation effects were present in men but not in women. CONCLUSIONS: We found that black-white differences in blood pressure partially explain the observed black-white disparity in CVD mortality, particularly among men. Our findings suggest that public health interventions targeting high blood pressure prevention and management could be important strategies for reducing racial disparities in CVD mortality.

2.
Biol Psychol ; 190: 108807, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38703810

ABSTRACT

Attentional bias toward weight-related stimuli plays a crucial role in the development and maintenance of body image disturbances. However, the temporal dynamics of attentional biases responsible for the previously reported behavioral effects caused by the task-irrelevant but spatial-relevant weight-related stimuli presented in the peripheral visual field among females with high weight dissatisfaction (HWD) remain unclear. The present study combined the modified dot-probe task and event-related potentials to explore the temporal dynamics of spatial attentional biases toward weight-related words among females with HWD. The results showed significantly larger N2pc amplitudes were elicited by fat-related and thin-related words than neutral words only in the HWD group. Moreover, only fat-related words elicited a significant PD for the HWD group, and the PD amplitudes were larger in the HWD group than in the control group. These findings revealed that weight-related words initially captured spatial allocation among females with HWD, and then fat-related words were actively suppressed after the initial capturing.

3.
Front Pharmacol ; 15: 1374183, 2024.
Article in English | MEDLINE | ID: mdl-38756380

ABSTRACT

The human voltage-gated sodium channel Nav1.7 is a widely proven target for analgesic drug studies. ProTx2, a 30-residue polypeptide from Peruvian green tarantula venom, shows high specificity to activity against human Nav1.7, suggesting its potential to become a non-addictive analgesic. However, its high sensitivity to human Nav1.4 raises concerns about muscle side effects. Here, we engineered three mutants (R13A, R13D, and K27Y) of ProTx2 to evaluate their pharmacological activities toward Nav1.7 and Nav1.4. It is demonstrated that the mutant R13D maintained the analgesic effect in mice while dramatically reducing its muscle toxicity compared with ProTx2. The main reason is the formation of a strong electrostatic interaction between R13D and the negatively charged amino acid residues in DII/S3-S4 of Nav1.7, which is absent in Nav1.4. This study advances our understanding and insights on peptide toxins, paving the way for safer, effective non-addictive analgesic development.

4.
Food Res Int ; 183: 114204, 2024 May.
Article in English | MEDLINE | ID: mdl-38760136

ABSTRACT

This study aimed to investigate the impact of three cooking ways (sous vide (SV), frying (FR) and roasting (RO)) on pork protein digestion characteristics under conditions simulating healthy adult (control, C) and elderly individuals with achlorhydria (EA). Changes in degree of hydrolysis (DH), SDS-PAGE profiles, zeta potential, particle size and secondary structure during digestion were evaluated. Our results revealed the EA condition markedly affected the protein digestion process of pork with different cooking ways. The DH values of SV (25.62%), FR (21.38%) and RO (19.40%) under the EA condition were significantly lower than those of under the control condition (38.32%, 33.00% and 30.86%, respectively). Moreover, differences were also observed among three cooking ways under the EA condition. For a given cooking way, the differences between control and EA conditions gradually diminished from the gastric to the intestinal phase. Under a certain digestion condition, SV maintained the highest degree of digestion throughout the process, particularly under the EA condition. Therefore, we conclude that pork cooked by sous vide is more recommendable for the elderly considering protein digestibility.


Subject(s)
Cooking , Digestion , Cooking/methods , Humans , Animals , Aged , Swine , Adult , Pork Meat/analysis , Particle Size , Hydrolysis , Meat Proteins
5.
Int J Biol Macromol ; 267(Pt 2): 131658, 2024 May.
Article in English | MEDLINE | ID: mdl-38636759

ABSTRACT

Moisture evaporation plays a crucial role in thermal management of human body, particularly in perspiration process. However, current fabrics aim for sweat removal and takes little account of basic thermo-regulation of sweat, resulted in their limited evaporation capacity and heat dissipation at moderate/intense scenarios. In this study, a hygroscopic cooling (h-cool) fabric based on multi-functional design, for personal perspiration management, was described. By using economic and effective weaving technology, directional moisture transport routes and heat conductive pathways were incorporated in the construct. The resultant fabric showed 10 times greater one-way transport index higher than cotton, Dri-FIT and Coolswitch fabrics, which contributed to highly enhanced evaporation ability (∼4.5 times than cotton), not merely liquid diffusion. As a result, h-cool fabric performed 2.1-4.2 °C cooling efficacy with significantly reduced sweat consuming than cotton, Dri-FIT and Coolswitch fabrics in the artificial sweating skin. Finally, the practical applications by actually wearing h-cool fabric showed great evaporative-cooling efficacy during different physical activities. Owing to the excellent thermo-moisture management ability, we expect the novel concept and construct of h-cool fabric can provide promising strategy for developing functional textiles with great "cool" and comfortable "dry" tactile sensation at various daily scenarios.


Subject(s)
Sweat , Textiles , Humans , Sweat/chemistry , Hot Temperature , Wettability , Sweating
6.
J Ethnopharmacol ; 328: 118038, 2024 Jun 28.
Article in English | MEDLINE | ID: mdl-38479544

ABSTRACT

ETHNOPHARMACOLOGICAL RELEVANCE: Bupleurum chinense DC.-Scutellaria baicalensis Georgi (BS) is a classic drug pair that has good clinical effects on depression and many tumors. However, the concurrent targeting mechanism of how the aforementioned drug pair is valid in the two distinct diseases, has not been clarified yet. AIM OF THE STUDY: The components of BS were detected by LC-MS, combined with network pharmacology to explore the active ingredients and common targeting mechanism of its multi-pathway regulation of BS in treating depression and CRC, and to validate the dual effects of BS using the CUMS mice model and orthotopic transplantation tumor mice model of CRC. RESULTS: Twenty-nine components were screened, 84 common gene targets were obteined, and the top 5 key targets including STAT3, PIK3R1, PIK3CA, AKT1, IL-6 were identified by PPI network. GO and KEGG analyses revealed that PI3K/AKT and JAK/STAT signaling pathways might play a crucial role of BS in regulating depression and CRC. BS significantly modulated CUMS-induced depressive-like behavior, attenuated neuronal damage, and reduced serum EPI and NE levels in CUMS model mice. BS improved the pathological histological changes of solid tumors and liver tissues and inhibited solid tumors and liver metastases in tumor-bearing mice. BS significantly decreased the proteins' expression of IL-6, p-JAK2, p-STAT3, p-PI3K, p-AKT1 in hippocampal tissues and solid tumors, and regulated the levels of IL-2, IL-6 and IL-10 in serum of two models of mice. CONCLUSION: BS can exert dual antidepressant and anti-CRC effects by inhibiting the expression of IL-6/JAK2/STAT3 and PI3K/AKT pathway proteins and regulating the release of inflammatory cytokines.


Subject(s)
Bupleurum , Colorectal Neoplasms , Drugs, Chinese Herbal , Liver Neoplasms , Animals , Mice , Network Pharmacology , Depression/drug therapy , Interleukin-6 , Phosphatidylinositol 3-Kinases , Proto-Oncogene Proteins c-akt , Scutellaria baicalensis , Disease Models, Animal , Colorectal Neoplasms/drug therapy , Molecular Docking Simulation , Drugs, Chinese Herbal/pharmacology , Drugs, Chinese Herbal/therapeutic use
7.
Gene ; 912: 148365, 2024 Jun 20.
Article in English | MEDLINE | ID: mdl-38485033

ABSTRACT

BACKGROUND: Hirschsprung's-associated enterocolitis (HAEC) is a prevalent complication of Hirschsprung's disease (HSCR). Zinc finger E-box binding homeobox 2 (ZEB2) and Notch-1/Jagged-2 are dysregulated in HSCR, but their role in HAEC progression remains poorly understood. We aimed to explore the role and underlying mechanism of enteric neural precursor cells (ENPCs) and the ZEB2/Notch-1/Jagged-2 pathway in HAEC development. METHODS: Colon tissues were collected from HSCR and HAEC patients. ENPCs were isolated from the HAEC group and stimulated by lipopolysaccharide (LPS). The expressions of ZEB2/Notch-1/Jagged-2 were measured using RT-qPCR and Western blot. Immunofluorescence and cell counting kit-8 assays were performed to assess the differentiation and proliferation of ENPCs. Inflammatory factors were measured by ELISA kits. Co-immunoprecipitation and bioinformatic analysis were used to explore the interaction between ZEB2 and Notch-1. Small interfering RNA and overexpression vectors were used to investigate the role and mechanism of ZEB2 and Notch-1 in regulating ENPCs' proliferation and differentiation during HAEC progression. RESULTS: We observed increased LPS in the colon tissues of HAEC, with downregulated ZEB2 expression and upregulated Notch-1/Jagged-2 expression. ZEB2 interacts with Notch-1. LPS treatment downregulated ZEB2 expression, upregulated Notch-1/Jagged-2 expression, and induced proliferation and differentiation disorders in ENPCs, which were reversed by the knockdown of Notch-1. Furthermore, overexpression of ZEB2 inhibited Notch-1/Jagged-2 signaling and ameliorated inflammation and dysfunction in LPS-induced ENPCs. Notch-1 overexpression enhanced LPS-induced dysfunction, but this effect was antagonized by the overexpression of ZEB2. CONCLUSION: Overexpression of ZEB2 ameliorates LPS-induced ENPCs' dysfunction via the Notch-1/Jagged-2 pathway, thus playing a role in HAEC.


Subject(s)
Enterocolitis , Hirschsprung Disease , Neural Stem Cells , Humans , Cell Proliferation , Colon/metabolism , Enterocolitis/complications , Enterocolitis/metabolism , Hirschsprung Disease/genetics , Lipopolysaccharides/pharmacology , Lipopolysaccharides/metabolism , Neural Stem Cells/metabolism , Zinc Finger E-box Binding Homeobox 2/genetics , Zinc Finger E-box Binding Homeobox 2/metabolism
8.
Int Immunopharmacol ; 132: 111946, 2024 May 10.
Article in English | MEDLINE | ID: mdl-38552292

ABSTRACT

Ensuring the homeostatic integrity of pulmonary artery endothelial cells (PAECs) is essential for combatting pulmonary arterial hypertension (PAH), as it equips the cells to withstand microenvironmental challenges. Spermidine (SPD), a potent facilitator of autophagy, has been identified as a significant contributor to PAECs function and survival. Despite SPD's observed benefits, a comprehensive understanding of its protective mechanisms has remained elusive. Through an integrated approach combining metabolomics and molecular biology, this study uncovers the molecular pathways employed by SPD in mitigating PAH induced by monocrotaline (MCT) in a Sprague-Dawley rat model. The study demonstrates that SPD administration (5 mg/kg/day) significantly corrects right ventricular impairment and pathological changes in pulmonary tissues following MCT exposure (60 mg/kg). Metabolomic profiling identified a purine metabolism disorder in MCT-treated rats, which SPD effectively normalized, conferring a protective effect against PAH progression. Subsequent in vitro analysis showed that SPD (0.8 mM) reduces oxidative stress and apoptosis in PAECs challenged with Dehydromonocrotaline (MCTP, 50 µM), likely by downregulating purine nucleoside phosphorylase (PNP) and modulating polyamine biosynthesis through alterations in S-adenosylmethionine decarboxylase (AMD1) expression and the subsequent production of decarboxylated S-adenosylmethionine (dcSAM). These findings advocate SPD's dual inhibitory effect on PNP and AMD1 as a novel strategy to conserve cellular ATP and alleviate oxidative injuries, thus providing a foundation for SPD's potential therapeutic application in PAH treatment.


Subject(s)
Endothelial Cells , Monocrotaline , Polyamines , Pulmonary Arterial Hypertension , Pulmonary Artery , Purines , Rats, Sprague-Dawley , Spermidine , Vascular Remodeling , Animals , Spermidine/pharmacology , Spermidine/therapeutic use , Purines/pharmacology , Polyamines/metabolism , Male , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Vascular Remodeling/drug effects , Pulmonary Artery/drug effects , Pulmonary Artery/metabolism , Pulmonary Artery/pathology , Rats , Pulmonary Arterial Hypertension/drug therapy , Pulmonary Arterial Hypertension/chemically induced , Pulmonary Arterial Hypertension/metabolism , Cells, Cultured , Oxidative Stress/drug effects , Apoptosis/drug effects , Purine-Nucleoside Phosphorylase/metabolism , Hypertension, Pulmonary/drug therapy , Hypertension, Pulmonary/chemically induced , Hypertension, Pulmonary/metabolism , Adenosylmethionine Decarboxylase/metabolism , Disease Models, Animal , Humans
9.
Biochemistry ; 63(6): 806-814, 2024 Mar 19.
Article in English | MEDLINE | ID: mdl-38422553

ABSTRACT

In the field of medical chemistry and other organic chemistry, introducing a methyl group into a designed position has been difficult to achieve. However, owing to the vigorous developments in the field of enzymology, methyltransferases are considered potential tools for addressing this problem. Within the methyltransferase family, Fur6 catalyzes the methylation of C3 of 1,2,4,5,7-pentahydroxynaphthalene (PHN) using S-adenosyl-l-methionine (SAM) as the methyl donor. Here, we report the catalytic mechanism and substrate specificity of Fur6 based on computational studies. Our molecular dynamics (MD) simulation studies reveal the reactive form of PHN and its interactions with the enzyme. Our hybrid quantum mechanics/molecular mechanics (QM/MM) calculations suggest the reaction pathway of the methyl transfer step in which the energy barrier is 8.6 kcal mol-1. Our free-energy calculations with a polarizable continuum model (PCM) indicate that the final deprotonation step of the methylated intermediate occurs after it is ejected into the water solvent from the active center pocket of Fur6. Additionally, our studies on the protonation states, the highest occupied molecular orbital (HOMOs), and the energy barriers of the methylation reaction for the analogs of PHN demonstrate the mechanism of the specificity to PHN. Our study provides valuable insights into Fur6 chemistry, contributing to a deeper understanding of molecular mechanisms and offering an opportunity to engineer the enzyme to achieve high yields of the desired product(s).


Subject(s)
Methyltransferases , Molecular Dynamics Simulation , Methyltransferases/metabolism , Substrate Specificity , Catalysis , Methylation , Quantum Theory
10.
Int J Biol Macromol ; 264(Pt 1): 130385, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38395290

ABSTRACT

Polysaccharides from Pumpkin (Cucurbita moschata Duchesne) (PPs) have many pharmacological activities, including anti-oxidant, immune, and intestinal microbiota regulation. These activities have provided some reminders of its potential therapeutic effect on ulcerative colitis (UC), but this has not yet been confirmed. This study preliminarily confirmed its significant anti-UC activity superior to Salicylazosulfapyridine. The average molecular weight of PPs was 3.10 × 105 Da, and PPs mainly comprised Mannose, Rhamnose, Galacturonic acid, Galactosamine, Glucose, and Xylose with molar ratios of 1.58:3.51:34.54:1.00:3.25:3.02. PPs (50, 100 mg/kg) could significantly resist dextran sodium sulfate induced UC on C57BL/6 mice by improving gut microbiota dysbiosis, such as the changes of relative abundance of Bacteroides, Culturomica, Mucispirillum, Escherichia-Shigella, Alistipes and Helicobacter. PPs also reverse the abnormal inflammatory reaction, including abnormal level changes of TNF-α, IFN-γ, IL-1ß, IL-4, IL-6, IL-10, and IL-18. Metabolomic profiling showed that PPs supplementation resulted in the participation of PPAR and MAPK pathways, as well as the increase of 5-hydroxyindole acetic acid (5-HIAA) level. 5-HIAA also exhibited individual and synergistic anti-UC activities in vivo. Furthermore, combination of PPs and 5-HIAA could also elevate the levels of PPARγ in nuclear and inhibit MAPK/NF-ĸB pathway in the colon. This study revealed that PPs and endogenous metabolite 5-HIAA might be developed to treat UC.


Subject(s)
Colitis, Ulcerative , Colitis , Cucurbita , Gastrointestinal Microbiome , Mice , Animals , Mice, Inbred C57BL , NF-kappa B , Hydroxyindoleacetic Acid , PPAR gamma , Colitis/chemically induced , Colitis/drug therapy , Bacteroidetes , Dietary Supplements , Dextran Sulfate , Disease Models, Animal , Colon
11.
Chemphyschem ; 25(6): e202300634, 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38415889

ABSTRACT

Acetylene (C2 H2 ) monitoring in real time and online is essential for erasing transformer risks and guaranteeing normal equipment operation and operator safety. This study examines the direct fabrication of ultrathin SnO2 nanowalls on Ag-Pd substrates using a simple solvothermal method that doesn't demand the use of any additional motivators or templates. The thickness and shape of the nanowalls can be controlled by varying the cetyl trimethyl ammonium bromide (CTAB) concentration in the solvent. As observed, the gas sensor (SnO2 -3) fabricated by 2.4 g CTAB exhibits superior gas-sensing features. This is primarily due to the hollow structure constructed by the arrangement of nanowalls, which delivers not only enough gas diffusion pathways but also enough reaction sites during the gas sensing processes. The findings suggest that low-cost SnO2 nanowalls created using a straightforward procedure could be taken into consideration as prospective candidates for use in industrial C2 H2 sensing applications.

12.
Drug Des Devel Ther ; 18: 475-491, 2024.
Article in English | MEDLINE | ID: mdl-38405578

ABSTRACT

Purpose: The underlying causes of pulmonary arterial hypertension (PAH) often remain obscure. Addressing PAH with effective treatments presents a formidable challenge. Studies have shown that Hydroxysafflor yellow A (HSYA) has a potential role in PAH, While the mechanism underlies its protective role is still unclear. The study was conducted to investigate the potential mechanisms of the protective effects of HSYA. Methods: Using databases such as PharmMapper and GeneCards, we identified active components of HSYA and associated PAH targets, pinpointed intersecting genes, and constructed a protein-protein interaction (PPI) network. Core targets were singled out using Cytoscape for the development of a model illustrating drug-component-target-disease interactions. Intersection targets underwent analysis for Gene Ontology (GO) functions and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Selected components were then modeled for target interaction using Autodock and Pymol. In vivo validation in a monocrotaline-induced PAH (MCT-PAH) animal model was utilized to substantiate the predictions made by network pharmacology. Results: We associated HSYA with 113 targets, and PAH with 1737 targets, identifying 34 mutual targets for treatment by HSYA. HSYA predominantly affects 9 core targets. Molecular docking unveiled hydrogen bond interactions between HSYA and several PAH-related proteins such as ANXA5, EGFR, SRC, PPARG, PGR, and ESR1. Conclusion: Utilizing network pharmacology and molecular docking approaches, we investigated potential targets and relevant human disease pathways implicating HSYA in PAH therapy, such as the chemical carcinogenesis receptor activation pathway and the cancer pathway. Our findings were corroborated by the efficacious use of HSYA in an MCT-induced rat PAH model, confirming its therapeutic potential.


Subject(s)
Chalcone , Chalcone/analogs & derivatives , Drugs, Chinese Herbal , Pulmonary Arterial Hypertension , Quinones , Humans , Animals , Rats , Pulmonary Arterial Hypertension/chemically induced , Pulmonary Arterial Hypertension/drug therapy , Vascular Remodeling , Molecular Docking Simulation , Chalcone/pharmacology
13.
Mol Cell Biochem ; 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38306011

ABSTRACT

Alkylation repair homolog protein 5 (ALKBH5) is reported to participate in infantile hemangioma (IH) progression. However, the underlying mechanism of ALKBH5 in IH remains unclear. Using qRT-PCR and Western blotting, ALKBH5, forkhead box F1 (FOXF1) and hexokinase 2 (HK-2) expressions in IH tissues and IH-derived endothelial cells XPTS-1 were assessed. The Me-RIP assay was used to analyze FOXF1 m6A level. CCK8, colony formation, flow cytometry and transwell assays were employed to determine IH cell viability, proliferation, apoptosis, migration and invasion. The interactions between YTH (YT521-B homology) domain 2 (YTHDF2), FOXF1 and HK-2 were analyzed by RIP, dual luciferase reporter gene assay and/or ChIP assay. The in vivo IH growth was evaluated in immunocompromised mice. FOXF1 was overexpressed in IH tissues, and its silencing inhibited IH cell proliferation, migration and invasion whereas promoting cell apoptosis in vitro. ALKBH5 upregulation facilitated FOXF1 mRNA stability and expression in IH cells in a m6A-YTHDF2-dependent manner. FOXF1 downregulation reversed the impact of ALKBH5 upregulation on IH cellular phenotypes. It also turned out that FOXF1 positively regulated HK-2 expression in IH cells through interacting with the HK-2 promoter. HK-2 upregulation abolished FOXF1 knockdown's inhibition on IH cell aggressive behaviors. ALKBH5 or FOXF1 silencing suppressed IH tumor development via HK-2 signaling in immunocompromised mice. ALKBH5 promoted FOXF1 expression m6A-YTHDF2 dependently, which in turn elevated HK-2 expression, thereby accelerating IH development.

14.
Sci Rep ; 14(1): 4422, 2024 02 23.
Article in English | MEDLINE | ID: mdl-38388534

ABSTRACT

The global diagnosis rate and mortality of gastric cancer (GC) are among the highest. Ferroptosis and iron-metabolism have a profound impact on tumor development and are closely linked to cancer treatment and patient's prognosis. In this study, we identified six PRDEGs (prognostic ferroptosis- and iron metabolism-related differentially expressed genes) using LASSO-penalized Cox regression analysis. The TCGA cohort was used to establish a prognostic risk model, which allowed us to categorize GC patients into the high- and the low-risk groups based on the median value of the risk scores. Our study demonstrated that patients in the low-risk group had a higher probability of survival compared to those in the high-risk group. Furthermore, the low-risk group exhibited a higher tumor mutation burden (TMB) and a longer 5-year survival period when compared to the high-risk group. In summary, the prognostic risk model, based on the six genes associated with ferroptosis and iron-metabolism, performs well in predicting the prognosis of GC patients.


Subject(s)
Ferroptosis , Stomach Neoplasms , Humans , Stomach Neoplasms/genetics , Ferroptosis/genetics , Risk Factors , Gene Expression , Iron , Prognosis
15.
J Public Health Policy ; 45(1): 86-99, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38238590

ABSTRACT

Diabetes is the most expensive chronic disease in the United States, and hospital inpatient care accounts for 30% of the total medical expenditures. Medical costs for people with limited resources are covered by Medicaid, a joint federal and state program, and its expansion that extent the coverage to those with incomes up to 138% of the federal poverty level. We investigated the impact of Medicaid expansion on diabetes hospitalizations by states and payer, among adults aged 19 to 64 years old, 5 years after the expansion. We found that Medicaid expansion decreased total diabetes hospitalization in most states and a diabetes hospitalization payer mix shifted from private insurance and uninsured to Medicaid. The percentage of diabetes hospitalizations paid by Medicaid increased by 11% (95% CI 7%, 16%), while the percentage paid by private insurance decreased by 6% (95% CI - 8%, - 3%) and the percentage of uninsured diabetes hospitalization decreased by 13% (95% CI - 18%, - 9%).


Subject(s)
Diabetes Mellitus , Medicaid , Adult , Humans , United States , Young Adult , Middle Aged , Patient Protection and Affordable Care Act , Hospitalization , Medically Uninsured , Diabetes Mellitus/epidemiology , Diabetes Mellitus/therapy
16.
EClinicalMedicine ; 67: 102372, 2024 Jan.
Article in English | MEDLINE | ID: mdl-38169790

ABSTRACT

Background: The mRNA vaccine has demonstrated significant effectiveness in protecting against SARS-CoV-2 during the pandemic, including against severe forms of the disease caused by emerging variants. In this study, we examined safety, immunogenicity, and relative efficacy of a heterologous booster of the lipopolyplex (LPP)-based mRNA vaccine (SW-BIC-213) versus a homologous booster of an inactivated vaccine (BBIBP) in Laos. Methods: In this phase 3 clinical trial, which was randomized, parallel controlled and double-blinded, healthy adults aged 18 years and above were recruited from the Southern Savannakhet Provincial Hospital and Champhone District Hospital. The primary outcomes were safety and immunogenicity, with efficacy as an exploratory endpoint. Participants who were fully immunized with a two-dose inactivated vaccine for more than 6 months were assigned equally to either the SW-BIC-213 group (25 µg) or BBIBP group. The primary safety endpoint was to describe the safety profile of all participants in each group up to 6 months post-booster immunization. The primary immunogenic outcome was to demonstrate the superiority of the neutralizing antibody response, in terms of geometric mean titers (GMTs) of SW-BIC-213, compared with BBIBP 28 days after the booster dose. The exploratory efficacy endpoint aimed to assess the relative efficacy of SW-BIC-213 compared to BBIBP against virologically confirmed symptomatic COVID-19 over a 6-month period. The trial was registered with ClinicalTrials.gov (NCT05580159). Findings: Between October 10, 2022, and January 13, 2023, 1200 participants were assigned to SW-BIC-213 group and 1203 participants in the BBIBP group. All adverse reactions observed during the study were tolerable, transient, and resolved spontaneously. Solicited local reactions were the main adverse reactions in both the SW-BIC-213 group (43.8%) and BBIBP group (14.8%) (p < 0.001). Heterologous boosting with SW-BIC-213 induced higher live virus neutralizing antibodies to SARS-CoV-2 wildtype and BA.5 strains with GMTs reaching 750.1 and 192.9 than homologous boosting with BBIBP with GMTs of 131.5 (p < 0.001) and 47.5 (p < 0.001) on day 29. The statistical findings revealed that, following a period of 14-day to 6-month after booster vaccination, the SW-BIC-213 group exhibited a relative vaccine efficacy (VE) of 70.1% (95% CI: 34.2-86.4) against symptomatic COVID-19 when compared to the BBIBP group. Interpretation: A heterologous booster with the COVID-19 mRNA vaccine SW-BIC-213 manifests a favorable safety profile and proves highly immunogenic and efficacious in preventing symptomatic COVID-19 in individuals who have previously received two doses of inactivated vaccine. Funding: Shanghai Strategic Emerging Industries Development Special Fund, Biomedical Technology Support Special Project of Shanghai "Science and Technology Innovation Action Plan", Shanghai Municipal Science and Technology Commission.

17.
Sci Rep ; 14(1): 2392, 2024 01 29.
Article in English | MEDLINE | ID: mdl-38287035

ABSTRACT

The overall picture of degloving skin and soft tissue injuries (DSTI) remains a blank space in China. Therefore, a retrospective study was designed to summarize the current situation of this injury. Patients diagnosed with DSTI hospitalized between 2013 and 2018 were identified from the Hospital Quality Monitoring System (HQMS) database, of whom demographics, injury characteristics, hospitalization and cost information were analyzed. A total of 62,709 patients were enrolled in this study. Male sex predominated, with a mean age of 43.01 ± 19.70 years. Peasants seemed to be the most vulnerable. East China and Hubei province had the most patients. The most and least frequently injured anatomic site were lower extremity and torso, respectively. Traffic-related accidents and summer accounted for the highest proportion in terms of injury mechanism and season. The operation rate of DSTI roughly showed a growing trend, and the average length of stay was 22.02 ± 29.73 days. At discharge, 0.93% of DSTI patients ended up in death. Medicine accounted mostly for hospitalization cost, while the proportion decreased year by year. More than half DSTI patients paid at their own charge. This study made a relatively detailed description of DSTI patients nationwide, and might provide enlightenments for better prevention and treatment.


Subject(s)
Inpatients , Soft Tissue Injuries , Humans , Male , Young Adult , Adult , Middle Aged , Retrospective Studies , Hospitalization , Skin , Soft Tissue Injuries/epidemiology , Soft Tissue Injuries/surgery
18.
Epidemiology ; 35(2): 263-272, 2024 Mar 01.
Article in English | MEDLINE | ID: mdl-38290145

ABSTRACT

BACKGROUND: Studies have suggested Medicaid expansion enacted in 2014 has resulted in a reduction in overall cardiovascular disease (CVD) mortality in the United States. However, it is unknown whether Medicaid expansion has a similar effect across race-ethnicity and sex. We investigated the effect of Medicaid expansion on CVD mortality across race-ethnicity and sex. METHODS: Data come from the behavioral risk factor surveillance system and the US Centers for Disease Control's Wide-ranging Online Data for Epidemiologic Research, spanning the period 2000-2019. We used the generalized synthetic control method, a quasi-experimental approach, to estimate effects. RESULTS: Medicaid expansion was associated with -5.36 (mean difference [MD], 95% confidence interval [CI] = -22.63, 11.91) CVD deaths per 100,000 persons per year among Blacks; -4.28 (MD, 95% CI = -30.08, 21.52) among Hispanics; -3.18 (MD, 95% CI = -8.30, 1.94) among Whites; -5.96 (MD, 95% CI = -15.42, 3.50) among men; and -3.34 (MD, 95% CI = -8.05, 1.37) among women. The difference in mean difference (DMD) between the effect of Medicaid expansion in Blacks compared with Whites was -2.18; (DMD, 95% CI = -20.20, 15.83); between that in Hispanics compared with Whites: -1.10; (DMD, 95% CI = -27.40, 25.20) and between that in women compared with men: 2.62; (DMD, 95% CI = -7.95, 13.19). CONCLUSIONS: Medicaid expansion was associated with a reduction in CVD mortality overall and in White, Black, Hispanic, male, and female subpopulations. Also, our study did not find any difference or disparity in the effect of Medicaid on CVD across race-ethnicity and sex-gender subpopulations, likely owing to imprecise estimates.


Subject(s)
Cardiovascular Diseases , Health Status Disparities , Female , Humans , Male , Cardiovascular Diseases/epidemiology , Ethnicity , Healthcare Disparities , Hispanic or Latino , Medicaid , United States/epidemiology , White , Black or African American , Racial Groups , Sex Factors
19.
Small ; : e2310972, 2024 Jan 28.
Article in English | MEDLINE | ID: mdl-38282180

ABSTRACT

Recently, aqueous zinc-ion batteries with conversion mechanisms have received wide attention in energy storage systems on account of excellent specific capacity, high power density, and energy density. Unfortunately, some characteristics of cathode material, zinc anode, and electrolyte still limit the development of aqueous zinc-ion batteries possessing conversion mechanism. Consequently, this paper provides a detailed summary of the development for numerous aqueous zinc-based batteries: zinc-sulfur (Zn-S) batteries, zinc-selenium (Zn-Se) batteries, zinc-tellurium (Zn-Te) batteries, zinc-iodine (Zn-I2 ) batteries, and zinc-bromine (Zn-Br2 ) batteries. Meanwhile, the reaction conversion mechanism of zinc-based batteries with conversion mechanism and the research progress in the investigation of composite cathode, zinc anode materials, and selection of electrolytes are systematically introduced. Finally, this review comprehensively describes the prospects and outlook of aqueous zinc-ion batteries with conversion mechanism, aiming to promote the rapid development of aqueous zinc-based batteries.

20.
Eur J Pharmacol ; 965: 176315, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38176636

ABSTRACT

Pulmonary arterial hypertension (PAH) is a complex and fatal cardio-pulmonary vascular disease. Decompensated right ventricular hypertrophy (RVH) caused by cardiomyocyte hypertrophy often leads to fatal heart failure, the leading cause of mortality among patients. Sodium butyrate (SB), a compound known to reduce cardiac hypertrophy, was examined for its potential effect and the underlying mechanism of SB on PAH-RVH. The in vivo study showed that SB alleviated RVH and cardiac dysfunction, as well as improved life span and survival rate in MCT-PAH rats. The in vivo and in vitro experiments showed that SB could attenuate cardiomyocyte hypertrophy by reversing the expressions of H19, let-7g-5p, insulin-like growth factor 1 receptor (IGF1 receptor), and pERK. H19 inhibition restored the level of let-7g-5p and prevented the overexpression of IGF1 receptor and pERK in hypertrophic cardiomyocytes. In addition, dual luciferase assay revealed that H19 demonstrated significant binding with let-7g-5p, acting as its endogenous RNA. Briefly, SB attenuated PAH-RVH by inhibiting the H19 overexpression, restoring the level of let-7g-5p, and hindering IGF1 receptor/ERK activation.


Subject(s)
Hypertension, Pulmonary , MicroRNAs , Pulmonary Arterial Hypertension , Humans , Rats , Animals , Hypertrophy, Right Ventricular , Pulmonary Arterial Hypertension/complications , Butyric Acid/pharmacology , Butyric Acid/therapeutic use , Hypertension, Pulmonary/metabolism , Familial Primary Pulmonary Hypertension , MicroRNAs/genetics , MicroRNAs/metabolism , Insulin-Like Growth Factor I
SELECTION OF CITATIONS
SEARCH DETAIL
...