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2.
BMC Health Serv Res ; 24(1): 580, 2024 May 03.
Article in English | MEDLINE | ID: mdl-38702754

ABSTRACT

BACKGROUND: This study aimed to assess COVID-19 vaccine confidence among healthcare personnel in the safety net sector of the United States and Puerto Rico. This study aimed to examine the extent to which increased knowledge and positive attitudes toward COVID-19 vaccine safety and efficacy were associated with healthcare workers' COVID-19 vaccination status and their recommendation of the vaccine to all patients. METHODS: Online survey data were collected from health care workers working in Free and Charitable Clinics across the United States and Federally Qualified Health Centers in Puerto Rico. The survey consisted of 62 questions covering various demographic measures and constructs related to healthcare workers' vaccination status, beliefs, and recommendations for COVID-19 vaccination. Statistical analyses, including multivariate analysis, were conducted to identify the factors associated with the COVID-19 vaccine status and recommendations among healthcare personnel. RESULTS: Among the 2273 respondents, 93% reported being vaccinated against COVID-19. The analysis revealed that respondents who believed that COVID-19 vaccines were efficacious and safe were three times more likely to be vaccinated and twice as likely to recommend them to all their patients. Respondents who believed they had received adequate information about COVID-19 vaccination were 10 times more likely to be vaccinated and four times more likely to recommend it to all their patients. CONCLUSIONS: The study results indicate that healthcare workers' confidence in COVID-19 vaccines is closely tied to their level of knowledge, positive beliefs, and attitudes about vaccine safety and efficacy. The study emphasizes the significance of healthcare workers feeling well informed and confident in their knowledge to recommend the vaccine to their patients. These findings have important implications for the development of strategies to boost COVID-19 vaccine confidence among healthcare workers and increase vaccine uptake among patients.


Subject(s)
COVID-19 Vaccines , COVID-19 , Health Personnel , Humans , COVID-19 Vaccines/administration & dosage , Puerto Rico , Female , Male , United States , Health Personnel/psychology , Health Personnel/statistics & numerical data , Adult , COVID-19/prevention & control , Middle Aged , Surveys and Questionnaires , Health Knowledge, Attitudes, Practice , SARS-CoV-2 , Safety-net Providers , Attitude of Health Personnel , Vaccination/psychology , Vaccination/statistics & numerical data
3.
BMJ Open Qual ; 13(2)2024 May 28.
Article in English | MEDLINE | ID: mdl-38806206

ABSTRACT

The clinical quality improvement initiatives, led by the organisation's Health Equity Working Group (HEWG), aim to support healthcare providers to provide equitable, quality hypertension care worldwide. After coordinating with the India team, we started monitoring the deidentified patient data collected through electronic health records between January and May 2021. After stratifying data by age, sex and residence location, the team found an average of 55.94% of our hypertensive patients control their blood pressure, with an inequity of 11.91% between male and female patients.The objective of this study was to assess the effectiveness of using clinical quality improvement to improve hypertension care in the limited-resourced, mobile healthcare setting in Mumbai slums. We used the model for improvement, developed by Associates in Process Improvement. After 9-month Plan-Do-Study-Act (PDSA) cycles, the average hypertensive patients with controlled blood pressure improved from 55.94% to 89.86% at the endpoint of the initiative. The gender gap reduced significantly from 11.91% to 2.19%. We continued to monitor the blood pressure and found that the average hypertensive patients with controlled blood pressure remained stable at 89.23% and the gender gap slightly increased to 3.14%. Hypertensive patients have 6.43 times higher chance of having controlled blood pressure compared with the preintervention after the 9-month intervention (p<0.001).This paper discusses the efforts to improve hypertension care and reduce health inequities in Mumbai's urban slums. We highlighted the methods used to identify and bridge health inequity gaps and the testing of PDSA cycles to improve care quality and reduce disparities. Our findings have shown that clinical quality improvement initiatives and the PDSA cycle can successfully improve health outcomes and decrease gender disparity in the limited-resource setting.


Subject(s)
Healthcare Disparities , Hypertension , Poverty Areas , Quality Improvement , Humans , India , Hypertension/therapy , Male , Female , Healthcare Disparities/statistics & numerical data , Healthcare Disparities/standards , Middle Aged , Adult , Aged , Urban Population/statistics & numerical data
4.
Nat Commun ; 15(1): 3901, 2024 May 09.
Article in English | MEDLINE | ID: mdl-38724505

ABSTRACT

Activation of the NF-κB pathway is strictly regulated to prevent excessive inflammatory and immune responses. In a well-known negative feedback model, IκBα-dependent NF-κB termination is a delayed response pattern in the later stage of activation, and the mechanisms mediating the rapid termination of active NF-κB remain unclear. Here, we showed IκBα-independent rapid termination of nuclear NF-κB mediated by CLK2, which negatively regulated active NF-κB by phosphorylating the RelA/p65 subunit of NF-κB at Ser180 in the nucleus to limit its transcriptional activation through degradation and nuclear export. Depletion of CLK2 increased the production of inflammatory cytokines, reduced viral replication and increased the survival of the mice. Mechanistically, CLK2 phosphorylated RelA/p65 at Ser180 in the nucleus, leading to ubiquitin‒proteasome-mediated degradation and cytoplasmic redistribution. Importantly, a CLK2 inhibitor promoted cytokine production, reduced viral replication, and accelerated murine psoriasis. This study revealed an IκBα-independent mechanism of early-stage termination of NF-κB in which phosphorylated Ser180 RelA/p65 turned off posttranslational modifications associated with transcriptional activation, ultimately resulting in the degradation and nuclear export of RelA/p65 to inhibit excessive inflammatory activation. Our findings showed that the phosphorylation of RelA/p65 at Ser180 in the nucleus inhibits early-stage NF-κB activation, thereby mediating the negative regulation of NF-κB.


Subject(s)
Cytoplasm , NF-KappaB Inhibitor alpha , NF-kappa B , Protein-Tyrosine Kinases , Transcription Factor RelA , Animals , Phosphorylation , NF-KappaB Inhibitor alpha/metabolism , NF-KappaB Inhibitor alpha/genetics , Mice , Transcription Factor RelA/metabolism , Humans , Protein-Tyrosine Kinases/metabolism , Protein-Tyrosine Kinases/genetics , NF-kappa B/metabolism , Cytoplasm/metabolism , Proteolysis , Cell Nucleus/metabolism , Virus Replication , HEK293 Cells , Signal Transduction , Mice, Inbred C57BL , Cytokines/metabolism , Active Transport, Cell Nucleus , Protein Serine-Threonine Kinases
5.
Bioresour Technol ; 403: 130843, 2024 May 20.
Article in English | MEDLINE | ID: mdl-38777233

ABSTRACT

The malic enzyme (ME) catalyzes the synthesis of L-malic acid (L-MA) from pyruvic acid and CO2 with NADH as the reverse reaction of L-MA decarboxylation. Carboxylation requires excess pyruvic acid, limiting its application. In this study, it was determined that CO2 was the carboxyl donor by parsing the effects of HCO3- and CO2, which provided a basis for improving the L-MA yield. Moreover, the concentration ratio of pyruvic acid to NADH was reduced from 70:1 to 5:1 using CO2 to inhibit decarboxylation and to introduce the ME mutant A464S with a 2-fold lower Km than that of the wild type. Finally, carboxylation was coupled with NADH regeneration, resulting in a maximum L-MA yield of 77 % based on the initial concentration of pyruvic acid. Strategic modifications, including optimal reactant ratios and efficient mutant ME, significantly enhanced L-MA synthesis from CO2, providing a promising approach to the biotransformation process.

6.
Anal Chim Acta ; 1311: 342714, 2024 Jul 04.
Article in English | MEDLINE | ID: mdl-38816153

ABSTRACT

BACKGROUND: Antibiotics residues can accelerate the growth of drug-resistant bacteria and harm the ecological environment. Under the effect of enrichment and biomagnification, the emergence of drug-resistant pathogenic bacteria may eventually lead to humans being ineffective to drugs in the face of bacterial or fungal disease infections in the future. It is urgent to develop an efficient separation medium and analytical method for simultaneous extraction and determination of antibiotics in the water environment. RESULTS: This work doped 2,6-Di-O-methyl-ß-cyclodextrin, randomly methyl-ß-cyclodextrin, 2-hydroxypropyl-ß-cyclodextrin with thymol:fatty acid respectively to construct non-covalent interaction-dominated pH-responsive ternary supramolecular deep eutectic solvents (SUPRADESs), which can undergo a hydrophilic/hydrophobic transition with aqueous phase to achieve an efficient microextraction. Semi-empirical method illustrated that SUPRADESs have a wide range of hydrogen bond receptor sites. We developed a SUPRADES-based analytical method combined with liquid chromatography-triple quadrupole mass spectrometry for the extraction and determination of trace quinolones and sulfonamides in wastewater. The overall limits of detection of the method were 0.0021-0.0334 ng mL-1 and the limits of quantification were 0.0073-0.1114 ng mL-1. The linearity maintained good in the spiked level of 0.01-100 ng mL-1 (R2 > 0.99). The overall enrichment factors of the method were 157-201 with lower standard deviations (≤8.7). SIGNIFICANCE: The method gave an extraction recovery of 70.1-115.3 % for 28 antibiotics in livestock farming wastewater samples from Zhejiang, China, at trace levels (minimum 0.5 ng mL-1). The results demonstrated that inducing the phase transition between SUPRADES and aqueous phase by adjusting pH for extraction is a novel and efficient pretreatment strategy. To our knowledge, this is the first application of cyclodextrin-based ternary SUPRADESs with pH-responsive reversible hydrophobicity-hydrophilicity transition behavior in wastewater analysis.


Subject(s)
Cyclodextrins , Deep Eutectic Solvents , Quinolones , Sulfonamides , Wastewater , Water Pollutants, Chemical , Wastewater/chemistry , Wastewater/analysis , Hydrogen-Ion Concentration , Water Pollutants, Chemical/analysis , Water Pollutants, Chemical/chemistry , Water Pollutants, Chemical/isolation & purification , Sulfonamides/chemistry , Sulfonamides/analysis , Sulfonamides/isolation & purification , Quinolones/chemistry , Quinolones/isolation & purification , Quinolones/analysis , Cyclodextrins/chemistry , Deep Eutectic Solvents/chemistry
7.
Int Immunopharmacol ; 136: 112195, 2024 May 30.
Article in English | MEDLINE | ID: mdl-38820965

ABSTRACT

Proper hydration and the clarity of the cornea are maintained through the crucial function of the corneal endothelium. Inflammation of the corneal endothelium, known as endotheliitis, can disrupt endothelial function, resulting in alterations to vision. Corneal endotheliitis is characterised by corneal oedema, the presence of keratic precipitates, inflammation within the anterior chamber, and occasionally, limbal injection, neovascularisation, and the concurrent or overlapping presence of uveitis. The aetiology of this condition is diverse, predominantly viral, but it may also be drug-induced, result from bacterial or fungal infections, be associated with systemic diseases and procedures, or remain idiopathic with no identifiable cause. To date, no standardised protocol for the treatment of this ocular disease exists, and in severe cases, corneal transplantation may be required. A 31-year-old male was transferred to our hospital for the management of corneal endothelial decompensation resulting from corneal endotheliitis. Hormonal therapy and antiviral medications proved ineffective, rendering the patient a candidate for corneal transplantation. As a final measure, treatment with the ROCK inhibitor netarsudil was initiated. The patient demonstrated significant improvement in symptoms, and the inflammation was successfully managed after nine months. In this study, a novel approach employing ROCK inhibitor therapy was utilised for the treatment of corneal endotheliitis, leading to marked recovery during patient follow-up. This case report represents the inaugural application of the ROCK inhibitor netarsudil in managing corneal endothelial decompensation attributed to corneal endotheliitis. These findings suggest that this method warrants consideration as a potential novel treatment option for similar conditions.

8.
Mol Cancer ; 23(1): 71, 2024 Apr 04.
Article in English | MEDLINE | ID: mdl-38575922

ABSTRACT

It is generally recognized that tumor cells proliferate more rapidly than normal cells. Due to such an abnormally rapid proliferation rate, cancer cells constantly encounter the limits of insufficient oxygen and nutrient supplies. To satisfy their growth needs and resist adverse environmental events, tumor cells modify the metabolic pathways to produce both extra energies and substances required for rapid growth. Realizing the metabolic characters special for tumor cells will be helpful for eliminating them during therapy. Cell death is a hot topic of long-term study and targeting cell death is one of the most effective ways to repress tumor growth. Many studies have successfully demonstrated that metabolism is inextricably linked to cell death of cancer cells. Here we summarize the recently identified metabolic characters that specifically impact on different types of cell deaths and discuss their roles in tumorigenesis.


Subject(s)
Carcinogenesis , Neoplasms , Humans , Cell Transformation, Neoplastic/genetics , Cell Death , Nutrients , Oxygen , Apoptosis
9.
Insect Mol Biol ; 2024 Apr 13.
Article in English | MEDLINE | ID: mdl-38613398

ABSTRACT

The silkworm (Bombyx mori) is an important model lepidopteran insect and can be used to identify pesticide resistance-related genes of great significance for biological control of pests. Uridine diphosphate glucosyltransferases (UGTs), found in all organisms, are the main secondary enzymes involved in the metabolism of heterologous substances. However, it remains uncertain if silkworm resistance to fenpropathrin involves UGT. This study observes significant variations in BmUGT expression among B. mori strains with variable fenpropathrin resistance post-feeding, indicating BmUGT's role in fenpropathrin detoxification. Knockdown of BmUGT with RNA interference and overexpression of BmUGT significantly decreased and increased BmN cell activity, respectively, indicating that BmUGT plays an important role in the resistance of silkworms to fenpropathrin. In addition, fenpropathrin residues were significantly reduced after incubation for 12 h with different concentrations of a recombinant BmUGT fusion protein. Finally, we verified the conservation of UGT to detoxify fenpropathrin in Spodoptera exigua: Its resistance to fenpropathrin decreased significantly after knocking down SeUGT. In a word, UGT plays an important role in silkworm resistance to fenpropathrin by directly degrading the compound, a function seen across other insects. The results of this study are of great significance for breeding silkworm varieties with high resistance and for biological control of pests.

10.
Eur J Med Chem ; 271: 116433, 2024 May 05.
Article in English | MEDLINE | ID: mdl-38678826

ABSTRACT

PD-1/PD-L1 pathway blockade is a promising immunotherapy for the treatment of cancer. In this manuscript, a series of triaryl compounds containing ester chains were designed and synthesized based on the pharmacophore studies of the lead BMS-1. After several SAR iterations, 22 showed the best biochemical activity binding to hPD-L1 with an IC50 of 1.21 nM in HTRF assay, and a KD value of 5.068 nM in SPR analysis. Cell-based experiments showed that 22 effectively promoted A549 cell death by restoring T-cell immune function. 22 showed significant in vivo antitumor activity in a 4T1 mouse model without obvious toxicity, with a TGI rate of 67.8 % (20 mg/kg, ip). Immunohistochemistry data indicated that 22 activates the immune activity in tumors. These results suggest that 22 is a promising compound for further development of PD-1/PD-L1 inhibitor for cancer therapy.


Subject(s)
Antineoplastic Agents , B7-H1 Antigen , Esters , Programmed Cell Death 1 Receptor , Humans , Animals , B7-H1 Antigen/antagonists & inhibitors , B7-H1 Antigen/metabolism , Programmed Cell Death 1 Receptor/antagonists & inhibitors , Programmed Cell Death 1 Receptor/metabolism , Mice , Structure-Activity Relationship , Antineoplastic Agents/pharmacology , Antineoplastic Agents/chemistry , Antineoplastic Agents/chemical synthesis , Molecular Structure , Esters/chemistry , Esters/pharmacology , Esters/chemical synthesis , Drug Screening Assays, Antitumor , Dose-Response Relationship, Drug , Cell Proliferation/drug effects , Mice, Inbred BALB C , Female , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/pathology , Immune Checkpoint Inhibitors/pharmacology , Immune Checkpoint Inhibitors/chemistry , Immune Checkpoint Inhibitors/chemical synthesis
11.
Cell Mol Biol (Noisy-le-grand) ; 70(4): 118-126, 2024 Apr 28.
Article in English | MEDLINE | ID: mdl-38678617

ABSTRACT

A growing number of studies suggest a positive association between obesity and the high incidence of papillary thyroid cancer (PTC), suggesting that the abnormal levels of adipokines associated with obesity may be a risk factor for these aggressive thyroid cancers, but the underlying regulatory mechanisms are not yet clear. We downloaded bulk RNA sequence data for subcutaneous adipose tissue (SAT) in obesity and healthy population and tumor tissues of PTC from GEO database. Through analysis of Differential Expression Genes (DEGs), Gene Set Variation Analysis (GSVA) and Weighted Correlation Network Analysis (WGCNA), we identified co-expressed genes between obesity and PTC, and their pathways were mainly enriched in the regulation of B-cells. Furthermore, through TCGA-THCA (thyroid carcinoma) cohorts analysis, we identified B-cell regulatory-related genes LEF1, TNFRSF13C, SHLD2 and SHLD3 as independent prognostic markers of PTC. Next, we explored the transcriptional regulation mechanism of the increased risk of PTC in obesity through analysis of DNA methylation CpGs data and single-cell RNA sequences (scRNA-seq) from GEO database. PTC-induced hypomethylation of the promoter region may be involved in the transcriptional regulation of these genes, while these genes were further identified in naive and regulatory B-cells of both diseases. Notably, both of the gene expressions in naive and regulatory B-cells showed high similarity in both diseases. Our data reveals the high frequency of PTC in obese populations may be explained by the comparable transcriptional patterns of naive and regulatory B-cells, and offers novel insights for the analysis of critical genes and underlying biological mechanisms for obesity and PTC.


Subject(s)
DNA Methylation , Gene Expression Regulation, Neoplastic , Obesity , Thyroid Cancer, Papillary , Thyroid Neoplasms , Humans , Obesity/genetics , Obesity/complications , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/metabolism , Thyroid Neoplasms/genetics , Thyroid Neoplasms/pathology , Thyroid Neoplasms/metabolism , DNA Methylation/genetics , Risk Factors , B-Lymphocytes/metabolism , Transcription, Genetic , Gene Regulatory Networks , Female , Male , Gene Expression Profiling , Prognosis
12.
Adv Sci (Weinh) ; : e2308384, 2024 Apr 18.
Article in English | MEDLINE | ID: mdl-38634607

ABSTRACT

Cell-specific transcriptional regulatory networks (TRNs) play vital roles in plant development and response to environmental stresses. However, traditional single-cell mono-omics techniques are unable to directly capture the relationships and dynamics between different layers of molecular information within the same cells. While advanced algorithm facilitates merging scRNA-seq and scATAC-seq datasets, accurate data integration remains a challenge, particularly when investigating cell-type-specific TRNs. By examining gene expression and chromatin accessibility simultaneously in 16,670 Arabidopsis root tip nuclei, the TRNs are reconstructed that govern root tip development under osmotic stress. In contrast to commonly used computational integration at cell-type level, 12,968 peak-to-gene linkage is captured at the bona fide single-cell level and construct TRNs at an unprecedented resolution. Furthermore, the unprecedented datasets allow to more accurately reconstruct the coordinated changes of gene expression and chromatin states during cellular state transition. During root tip development, chromatin accessibility of initial cells precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for subsequent differentiation steps. Pseudo-time trajectory analysis reveal that osmotic stress can shift the functional differentiation of trichoblast. Candidate stress-related gene-linked cis-regulatory elements (gl-cCREs) as well as potential target genes are also identified, and uncovered large cellular heterogeneity under osmotic stress.

13.
Nucleic Acids Res ; 52(9): 4843-4856, 2024 May 22.
Article in English | MEDLINE | ID: mdl-38647109

ABSTRACT

Spatial transcriptome technologies have enabled the measurement of gene expression while maintaining spatial location information for deciphering the spatial heterogeneity of biological tissues. However, they were heavily limited by the sparse spatial resolution and low data quality. To this end, we develop a spatial location-supervised auto-encoder generator STAGE for generating high-density spatial transcriptomics (ST). STAGE takes advantage of the customized supervised auto-encoder to learn continuous patterns of gene expression in space and generate high-resolution expressions for given spatial coordinates. STAGE can improve the low quality of spatial transcriptome data and smooth the generated manifold of gene expression through the de-noising function on the latent codes of the auto-encoder. Applications to four ST datasets, STAGE has shown better recovery performance for down-sampled data than existing methods, revealed significant tissue structure specificity, and enabled robust identification of spatially informative genes and patterns. In addition, STAGE can be extended to three-dimensional (3D) stacked ST data for generating gene expression at any position between consecutive sections for shaping high-density 3D ST configuration.


Subject(s)
Gene Expression Profiling , Transcriptome , Transcriptome/genetics , Gene Expression Profiling/methods , Humans , Animals , Algorithms , Software
14.
Biomed Pharmacother ; 175: 116519, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38663104

ABSTRACT

OBJECTIVES: To elucidate the therapeutic effects and mechanisms of Atractylodes macrocephala extract crystallize (BZEP) and BZEP self-microemulsion (BZEPWR) on metabolic dysfunction-associated fatty liver disease (MAFLD) induced by "high sugar, high fat, and excessive alcohol consumption" based on the gut-liver axis HDL/LPS signaling pathway. METHODS: In this study, BZEP and BZEPWR were obtained via isolation, purification, and microemulsification. Furthermore, an anthropomorphic MAFLD rat model of "high sugar, high fat, and excessive alcohol consumption" was established. The therapeutic effects of BZEPWR and BZEP on the model rats were evaluated in terms of liver function, lipid metabolism (especially HDL-C), serum antioxidant indexes, and liver and intestinal pathophysiology. To determine the lipoproteins in the serum sample, the amplitudes of a plurality of NMR spectra were derived via deconvolution of the composite methyl signal envelope to yield HDL-C subclass concentrations. The changes in intestinal flora were detected via 16 S rRNA gene sequencing. In addition, the gut-liver axis HDL/LPS signaling pathway was validated using immunohistochemistry, immunofluorescence, and western blot. RESULTS: The findings established that BZEPWR and BZEP improved animal signs, serum levels of liver enzymes (ALT and AST), lipid metabolism (TC, TG, HDL-C, and LDL-C), and antioxidant indexes (GSH, SOD, and ROS). In addition, pathological damage to the liver, colon, and ileum was ameliorated, and the intestinal barrier function of the model rats was restored. At the genus level, BZEPWR and BZEP exerted positive effects on beneficial bacteria, such as Lactobacillus and norank_f__Muribaculaceae, and inhibitory effects on harmful bacteria, such as unclassified_f__Lachnospiraceae and Blautia. Twenty HDL-C subspecies were detected, and their levels were differentially increased in both BZEPWR and BZEP groups, with BZEPWR exhibiting a stronger elevating effect on specific HDL-C subspecies. Also, the gut-liver axis HDL/LPS signaling pathway was studied, which indicated that BZEPWR and BZEP significantly increased the expressions of ABCA1, LXR, occludin, and claudin-1 proteins in the gut and serum levels of HDL-C. Concomitantly, the levels of LPS in the serum and TLR4, Myd88, and NF-κB proteins in the liver were decreased. CONCLUSION: BZEPWR and BZEP exert restorative and reversal effects on the pathophysiological damage to the gut-liver axis in MAFLD rats, and the therapeutic mechanism may be related to the regulation of the intestinal flora and the HDL/LPS signaling pathway.


Subject(s)
Atractylodes , Emulsions , Gastrointestinal Microbiome , Lipopolysaccharides , Liver , Plant Extracts , Rats, Sprague-Dawley , Signal Transduction , Animals , Signal Transduction/drug effects , Male , Rats , Liver/drug effects , Liver/metabolism , Atractylodes/chemistry , Plant Extracts/pharmacology , Gastrointestinal Microbiome/drug effects , Lipoproteins, HDL/blood , Disease Models, Animal , Lipid Metabolism/drug effects , Fatty Liver/drug therapy , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Antioxidants/pharmacology
15.
World J Oncol ; 15(2): 209-222, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38545470

ABSTRACT

Background: DNA damage-induced apoptosis suppressor (DDIAS) has recently been discovered to induce cancer progression, but its functions and mechanisms in glioma have not been well studied. Methods: DDIAS expression in glioma tissues was analyzed by the Gene Expression Profiling Interactive Analysis server (GEPIA) and the Gene Expression database of Normal and Tumor tissue 2 (GENT2) databases. The role of DDIAS in glioma progression was studied by short hairpin RNA (shRNA) targeting DDIAS. The effects of DDIAS on glioma cell viability, cell proliferation, invasion, migration, and tumor sphere formation were determined by cell counting kit-8 (CCK-8), EdU, Transwell, tumor spheroid formation, extreme limiting dilution analysis assays in vitro and xenograft model construction in vivo. In addition, RNA sequencing and further functional experiments were used to analyze the DDIAS regulatory mechanism in glioma. Results: We found that DDIAS was highly expressed in glioma and that upregulated DDIAS indicated poor prognosis. Functionally, DDIAS knockdown inhibited glioma cell viability, cell proliferation, invasion and migration in vitro and tumor growth in vivo. In addition, lymphoid enhancer-binding factor 1 (LEF1) was identified as the downstream effector of DDIAS by RNA sequencing. DDIAS downregulation inhibited LEF1 mRNA and protein expression. The expression of DDIAS and LEF1 was positively correlated, and LEF1 overexpression rescued the inhibitory phenotype induced by DDIAS downregulation. We further showed that DDIAS downregulation inhibited cyclin A1, vimentin and the stemness-related factor CD133 and decreased the sphere formation capability, but these features were rescued by upregulation of LEF1. Conclusion: Taken together, these findings suggest that DDIAS promotes glioma progression and stemness by inducing LEF1 expression, proving that DDIAS may be a potential target for the treatment of glioma.

16.
Exp Eye Res ; 242: 109857, 2024 May.
Article in English | MEDLINE | ID: mdl-38479724

ABSTRACT

Penetrating keratoplasty remains the most common treatment to restore vision for corneal diseases. Immune rejection after corneal transplantation is one of the major causes of graft failure. In recent years, Rho-associated protein kinase (ROCK) inhibitors have been found to be associated with the activation of the STATs pathway and are widely studied in autoimmune diseases. Therefore, it may be possible that the ROCK inhibitors also participate in the local and systemic immune regulation in corneal transplantation through activation of the STATs pathway and affect the CD4+ T cell differentiation. This study aimed to explore the role of ROCK-STATs pathway in the occurrence of immune rejection in corneal transplantation by applying Y27632, a ROCK inhibitor, to the recipient mice and peripheral CD4+ T cells. We found that Y27632 significantly up-regulated the phosphorylation level of STAT5 in both spleen and lymph nodes, down-regulated the phosphorylation level of STAT3 in the CD4+ T cells in the spleen. It also increased the proportion of CD4+CD25+Foxp3+Helios+ Tregs while decreased CD4+IL17A+ -Th17 cells. Moreover, Y27632 also reduced the proportion of dendritic cells in both spleen and lymph nodes, as well as the expression level of CD86 on their surfaces in the spleen, while the proportion of macrophages was not affected. The expression levels of ROCK1, ROCK2, CD11c and IL-17A mRNA were also found to be low in the graft tissue while the expression of Helios was upregulated. Rho-kinase inhibitor can modulate the balance of Tregs/Th17 by regulating the phosphorylation levels of both STAT3 and STAT5, thereby inhibiting the occurrence of immune rejection in allogeneic corneal transplantation.


Subject(s)
Amides , CD4-Positive T-Lymphocytes , Graft Rejection , Mice, Inbred BALB C , Mice, Inbred C57BL , Pyridines , STAT3 Transcription Factor , STAT5 Transcription Factor , rho-Associated Kinases , Animals , Mice , Graft Rejection/metabolism , Graft Rejection/prevention & control , rho-Associated Kinases/antagonists & inhibitors , CD4-Positive T-Lymphocytes/immunology , STAT3 Transcription Factor/metabolism , STAT5 Transcription Factor/metabolism , Amides/pharmacology , Amides/therapeutic use , Pyridines/pharmacology , Pyridines/therapeutic use , Disease Models, Animal , Phosphorylation , Flow Cytometry , Keratoplasty, Penetrating , Blotting, Western , Corneal Transplantation , Male
17.
J Integr Med ; 22(2): 163-179, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38519277

ABSTRACT

BACKGROUND: Ginkgo biloba L. preparations (GBLPs) are a class of Chinese herbal medicine used in the adjuvant treatment of ischemic stroke (IS). Recently, several systematic reviews (SRs) and meta-analyses (MAs) of GBLPs for IS have been published. OBJECTIVE: This overview aims to assess the quality of related SRs and MAs. SEARCH STRATEGY: PubMed, Embase, Cochrane Library, Web of Science, Chinese Biological Medicine, China National Knowledge Infrastructure, Wanfang, and Chinese Science and Technology Journals databases were searched from their inception to December 31, 2022. INCLUSION CRITERIA: SRs and MAs of randomized controlled trials (RCTs) that explored the efficacy of GBLPs for patients with IS were included. DATA EXTRACTION AND ANALYSIS: Two independent reviewers extracted data and assessed the methodological quality, risk of bias (ROB), reporting quality, and credibility of evidence of the included SRs and MAs using A Measurement Tool to Assess Systematic Reviews 2 (AMSTAR 2), Risk of Bias in Systematic Reviews (ROBIS), the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA), and the Grading of Recommendations Assessment, Development and Evaluation (GRADE), respectively. Additionally, descriptive analysis and data synthesis were conducted. RESULTS: Twenty-nine SRs/MAs involving 119 outcomes were included in this review. The overall methodological quality of all SRs/MAs was critically low based on AMSTAR 2, and 28 had a high ROB based on the ROBIS. According to the PRISMA statement, the reporting items of the included SRs/MAs are relatively complete. The results based on GRADE showed that of the 119 outcomes, 8 were rated as moderate quality, 24 as low quality, and 87 as very low quality. Based on the data synthesis, GBLPs used in conjunction with conventional treatment were superior to conventional treatment alone for decreasing neurological function scores. CONCLUSION: GBLPs can be considered a beneficial supplemental therapy for IS. However, because of the low quality of the existing evidence, high-quality RCTs and SRs/MAs are warranted to further evaluate the benefits of GBLPs for treating IS. Please cite this article as: Meng TT, You YP, Li M, Guo JB, Song XB, Ding JY, Xie XL, Li AQ, Li SJ, Yin XJ, Wang P, Wang Z, Wang BL, He QY. Chinese herbal medicine Ginkgo biloba L. preparations for ischemic stroke: An overview of systematic reviews and meta-analyses. J Integr Med. 2024;22(2): 163-179.


Subject(s)
Drugs, Chinese Herbal , Humans , Drugs, Chinese Herbal/therapeutic use , Ginkgo biloba , China
18.
Pest Manag Sci ; 2024 Mar 15.
Article in English | MEDLINE | ID: mdl-38488318

ABSTRACT

BACKGROUND: Voltage-dependent anion-selective channels (VDACs) serve as pore proteins within the mitochondrial membrane, aiding in the regulation of cell life and cell death. Although the occurrence of cell death is crucial for defense against virus infection, the function played by VDAC in Bombyx mori, in response to the influence of Bombyx mori nucleopolyhedrovirus (BmNPV), remains unclear. RESULTS: BmVDAC was found to be relatively highly expressed both during embryonic development, and in the Malpighian tubule and midgut. Additionally, the expression levels of BmVDAC were found to be different among silkworm strains with varying levels of resistance to BmNPV, strongly suggesting a connection between BmVDAC and virus infection. To gain further insight into the function of BmVDAC in BmNPV, we employed RNA interference (RNAi) to silence and overexpress it by pIZT/V5-His-mCherry. The results revealed that BmVDAC is instrumental in developing the resistance of host cells to BmNPV infection in BmN cell-line cells, which was further validated as likely to be associated with initiating programmed cell death (PCD). Furthermore, we evaluated the function of BmVDAC in another insect, Spodoptera exigua. Knockdown of the BmVDAC homolog in S. exigua, SeVDAC, made the larvae more sensitive to BmNPV. CONCLUSION: We have substantiated the pivotal role of BmVDAC in conferring resistance against BmNPV infection, primarily associated with the initiation of PCD. The findings of this study shine new light on the molecular mechanisms governing the silkworm's response to BmNPV infection, thereby supporting innovative approaches for pest biocontrol. © 2024 Society of Chemical Industry.

19.
Org Lett ; 26(7): 1463-1467, 2024 Feb 23.
Article in English | MEDLINE | ID: mdl-38349252

ABSTRACT

Arene-tethered diols constitute a valuable class of structural motifs of drug and bioactive natural product molecules. In this study, a regioselective protocol for olefination and arylation of arene-tethered 1,2-diols and 1,3-diols has been developed using easily foldable acetal structures for attaching pyridine and nitrile directing groups. The method overcomes the steric hindrance effect of the short-chain diols and affords products in high yield and regioselectivity. This efficient cascaded catalysis has been successfully utilized in the syntheses of natural products such as peucedanol, decursinol, and marmesin.

20.
J Cosmet Dermatol ; 23(5): 1891-1904, 2024 May.
Article in English | MEDLINE | ID: mdl-38362670

ABSTRACT

BACKGROUND: Dendrobium officinale flowers (DOF) have the effects of antiaging and nourishing yin, but it lacks pharmacological research on skin aging. OBJECTIVE: Confirming the role of DOF in delaying skin aging based on the "in vitro animal-human" model. METHODS: In this experiment, three kinds of free radical scavenging experiments in vitro, D-galactose-induced aging mouse model, and human antiaging efficacy test were used to test whether DOF can improve skin aging through anti-oxidation. RESULTS: In vitro experiment shows that DOF has certain scavenging effect on 2,2-diphenyl-1-picrylhydrazyl (DPPH) free radical, hydroxyl free radical, and superoxide free radical, and its IC50 is 0.2090 µg/mL, 15.020, and 1.217 mg/mL respectively. DOF can enhance the activities of T-AOC, SOD, CAT, and GSH Px in the serum of aging mice, increase the content of GSH, and reduce the content of MDA when administered with DOF of 1.0, 2.0, and 4.0 g/kg for 6 weeks. In addition, it can enhance the activity of SOD in the skin of aging mice, increase the content of Hyp, and decrease the content of MDA, activated Keap1/Nrf2 pathway in the skin of aging mice. Applying DOF with a concentration of 0.2 g/mL on the face for 8 weeks can significantly improve the skin water score and elasticity value, reduce facial wrinkles, pores, acne, and UV spots, and improve the facial brown spots and roughness. CONCLUSION: DOF can significantly improve skin aging caused by oxidative stress, and its mechanism may be related to scavenging free radicals in the body and improving skin quality.


Subject(s)
Dendrobium , Flowers , Oxidative Stress , Plant Extracts , Skin Aging , Skin , Skin Aging/drug effects , Animals , Dendrobium/chemistry , Flowers/chemistry , Plant Extracts/pharmacology , Plant Extracts/administration & dosage , Oxidative Stress/drug effects , Mice , Humans , Skin/drug effects , Skin/metabolism , Antioxidants/pharmacology , Antioxidants/administration & dosage , Male , Female
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