Your browser doesn't support javascript.
loading
Show: 20 | 50 | 100
Results 1 - 20 de 759
Filter
1.
Diabetes Metab Syndr Obes ; 17: 3547-3556, 2024.
Article in English | MEDLINE | ID: mdl-39328264

ABSTRACT

Background: Approximately 10-20% of individuals with non-alcoholic fatty liver disease (NAFLD) are lean, and the underlying pathophysiology is not yet understood. This study aims to explore the characteristics and the diagnostic value of triglyceride-glucose index (TyG) in early diagnosis of lean NAFLD. Methods: 99 patients with lean NAFLD and 1891 healthy controls were included in the health examination. The characteristics were compared between groups. Restricted cubic spline was utilized to analyze the relationship between TyG index and the risk of lean NAFLD. Logistic regression and receiver operating curve (ROC) were applied to explore the diagnostic value of TyG index for lean NAFLD. Results: Overall, 99 (4.97%) patients had lean NAFLD. Patients with lean NAFLD have significant abnormal glycolipid metabolism and higher TyG index. Restriction cube spline analysis showed a significant dose-response relationship between the TyG index and risk of lean NAFLD. After adjusting for confounders, the relationship remained and the risk of developing lean NAFLD increased 2.99 times for per unit increase of TyG index (95% CI: 1.94, 4.67, P<0.001). The areas under the ROC of the TyG index for lean NAFLD detection were 0.851 (0.815 to 0.886). Conclusion: The TyG index is positively associated with the risk of developing lean NAFLD and could be a useful marker for early diagnosis of lean NAFLD.

2.
Molecules ; 29(18)2024 Sep 11.
Article in English | MEDLINE | ID: mdl-39339300

ABSTRACT

The utilization of MnO anodes with high storage capacity is significantly hindered by rapid capacity fading and inadequate rate capability, stemming from substantial volume fluctuations and low electrical conductivity. Crafting a composite comprising sulfur and fluorine co-modified MnO nanoparticles integrated with sulfur and nitrogen co-doped carbon matrices promises enhanced electrochemical performance yet poses formidable obstacles. Here, we present a straightforward synthetic strategy for in situ growth of sulfur and fluorine co-modified MnO nanoparticles onto sulfur and nitrogen co-doped carbon scaffolds. This integration effectively mitigates volume variations and enhances electrical conductivity. As a result, the SF-MnO/SNC composite demonstrates remarkable cycling stability and rate capability when employed as a lithium-ion battery anode. Remarkably, it achieves a high reversible capacity of 975 mAh g-¹ after 80 cycles at 0.1 A g-¹ and retains a substantial capacity of 498 mAh g-¹ even at a high rate of 2.0 A g-¹. The concise synthesis method and exceptional rate properties render the SF-MnO/SNC composite a promising anode material for lithium-ion batteries. The strategy of simultaneously doping oxides and carbon will bring new ideas to the research of oxide anodes.

3.
J Hazard Mater ; 480: 135870, 2024 Sep 16.
Article in English | MEDLINE | ID: mdl-39298961

ABSTRACT

Environmental persistent free radicals (EPFRs) derived from chlorophenols, triggered by light or heat exposure, pose significant ecological concerns, yet the impact of chlorine substituents on EPFRs formation and reactivity remains inadequately understood. Through an intentional synthesis of chlorophenol-derived EPFRs with varying chlorine contents and positioning, we elucidated the role of chlorine in the photoactivation of molecular oxygen. Our combined experimental and theoretical analysis reveals that these EPFRs are primarily oxygen-centered phenoxy radicals, establishing a direct link between chlorine substitution patterns and their ability to activate molecular oxygen under visible light. Increased chlorine content enhances EPFRs formation by elevating the positive charge on the phenolic hydroxyl group's hydrogen atom, facilitating its removal. Moreover, the capability of EPFRs to activate molecular oxygen was directly correlated with chlorine content, with 2,3,5,6-tetrachlorophenol-derived EPFRs showcasing the highest activity. This activity is attributed to their structural propensity for TCSQ·- species generation. Furthermore, our study established a significant correlation between the toxicity and activity of EPFRs, emphasizing the critical role of halogen substituents in determining the reactivity of EPFRs. These insights contribute to our understanding of their environmental and toxicological ramifications, underscoring the imperative for continued research aimed at mitigating their detrimental impacts.

4.
Neuroscience ; 2024 Sep 18.
Article in English | MEDLINE | ID: mdl-39304022

ABSTRACT

The neuroinflammatory response promotes secondary brain injury after traumatic brain injury (TBI). Triggering receptor expressed on myeloid cells 1 (TREM1) is a key regulator of inflammation. However, the role of TREM1 in TBI is poorly studied. The purpose of this study was to investigate the role of TREM1 in TBI and the possible underlying mechanism. We found that the protein expression of TREM1 significantly increased after TBI in rats, and the TREM1 protein localized to microglia. Inhibition of the TREM1 protein with LP17 significantly blocked ERK phosphorylation and reduced cytoplasmic phospholipase A2 (cPLA2) protein expression and phosphorylation. In addition, LP17-mediated TREM1 inhibition significantly reduced the protein expression of iNOS and increased the protein expression of Arg1 . Moreover, after TREM1 was inhibited, the secretion of the proinflammatory factors TNF-α and IL-1ß was significantly reduced, while the secretion of the anti-inflammatory factors IL-4 and IL-10 was significantly increased. Additionally, inhibition of TREM1 by LP17 significantly reduced neuronal apoptosis and ameliorated nerve dysfunction in TBI model rats. In conclusion, our findings suggest that TREM1 enhances neuroinflammation and promotes neuronal apoptosis after TBI, and these effects may be partly mediated via the ERK/cPLA2 signalling pathway.

5.
Quant Imaging Med Surg ; 14(9): 6635-6646, 2024 Sep 01.
Article in English | MEDLINE | ID: mdl-39281133

ABSTRACT

Background: Metabolic syndrome (MetS) has complex effects on bone health, and dual-energy spectral computed tomography (CT) has become increasingly valuable for bone quantification. However, the relationship between bone base material pairs (BMPs) and abdominal fat volume in patients with MetS remains underexplored. This study thus aimed to analyze the relationship between abdominal fat volume and various bone BMPs using dual-energy spectral CT in young and middle-aged patients with MetS. Methods: Patients with MetS who underwent sleeve gastrectomy at the Center of Obesity and Metabolic Diseases, Beijing Shijitan Hospital, Capital Medical University, from June to November 2021 were retrospectively collected. The abdominal fat measurements and BMPs were acquired using dual-energy spectral CT imaging. These included the volumes of total abdominal fat (TAF), abdominal visceral fat (AVF), and abdominal subcutaneous fat (ASF), as well as bone densities based on hydroxyapatite (water), i.e., HAP (water), and calcium (water), i.e., Ca (water), BMPs. After grouping the patients by sex, we analyzed the differences in clinical and imaging features. The correlation between the clinical and imaging parameters of patients with MetS was evaluated with Pearson correlation coefficients. Age- and sex-adjusted partial correlation analysis between fat volume and bone BMPs was conducted for patients of different sexes. Additionally, multiple linear regression analyses were performed with age, sex, and TAF volume as the independent variables and with Ca (water) and HAP (water) as dependent variables. Results: A total of 112 young and middle-aged patients with MetS were included in this study, including 85 females and 27 males. Compared to male patients with MetS, the females with MetS exhibited higher lumbar Ca (water) and HAP (water) BMPs, with lower volumes of TAF and AVF and a smaller abdominal circumference (P<0.01). The volumes of TAF, AVF, and ASF were negatively correlated with the average Ca (water) and HAP (water) BMPs in the first to third lumbar vertebrae (L1-L3) (P<0.05). Ca (water) and HAP (water) BMPs decreased with age and increasing TAF volume (P<0.001). The fitted equations for the relationship between bone BMPs with age, sex, and TAF volume were as follows: (I) bone Ca (water) BMP = 76.469 - 0.500 age + 6.762 sex - 0.002 TAF volume; (II) bone HAP (water) BMP =171.704 - 1.138 age + 11.825 sex - 0.004 TAF volume. Conclusions: In young and middle-aged patients with MetS, the abdominal fat volume was negatively correlated with lumbar bone Ca (water) and HAP (water) BMPs, implying that increased abdominal fat volume may play a crucial role in the pathogenesis of osteopenia among those with MetS. The reduction of bone Ca (water) and HAP (water) with high abdominal fat volume may hold clinical significance for fracture risk in individuals with MetS.

6.
Health Sci Rep ; 7(9): e70050, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39221046

ABSTRACT

Background: Complications such as forearm hematoma after coronary intervention through the radial artery are a common complication. Material and methods: By observing, describing, and analyzing the pictures taken during clinical diagnosis and consultation, we summarize the prevention, treatment, and nursing of forearm hematoma after percutaneous coronary intervention, to provide reference for the nursing of patients with forearm hematoma. Results: We have innovatively summarized the risk classification of forearm hematoma and the three key time points for preventing hematoma. Conclusion: Complications such as forearm hematoma after coronary intervention through the radial artery are a common complication. We have innovatively summarized the risk classification of forearm hematoma and the three key time points for preventing hematoma, providing reference for the prevention and management of forearm hematoma in clinical practice. For patients undergoing transradial coronary intervention, the three key time points for preventing hematoma and symptomatic management based the risk classification of forearm hematoma are crucial.

7.
Nurs Open ; 11(9): e2231, 2024 Sep.
Article in English | MEDLINE | ID: mdl-39235127

ABSTRACT

AIM: This study analysed and summarized the correlation between various indicators of ICU nurses' personal lives, hospital work situation, social opinion, psychological assessment, and their intention to resign. DESIGN: A descriptive quantitative study. METHODS: This study was a multicentre questionnaire on factors influencing intensive care unit (ICU) nurses' intention to resign. This study was completed through the Critical Care E Institute (CCEI) and China Calm Therapy Research Group Academic Organization (CNCSG) by contacting ICU nurses in three hospitals in 34 provinces in China. The questionnaire was in the form of a cell phone WeChat scan code. The survey included 22 indicators, including basic information about nurses (marital and child status, personal income, etc.), hospital work (weekly working hours, night shift, hospital environment, etc.), and psychological symptoms. RESULTS: A total of 1904 nurses were included in this study. Among them, 1060 (55.67%) had the intention to resign. In this study, among the 22 indicators involved, 16 factors, including hospital work hours, job title, satisfaction with current income, having children, and evaluation of the hospital, significantly impact nurses' intentions to resign (all p < 0.05). Logistic regression analysis showed that six indicators influenced nurses' choice of resignation intention (all p < 0.05), including hospital work time, professional title, income satisfaction, hospital work pride, satisfaction of nurses with the compassion and care given to them by their hospitals, and career vision score. The ROC curve showed that all six indicators were <0.70, but the model receiver operating characteristic (ROC) curve constructed for the indicators was 0.756. In China, increasing the income of ICU nurses, fostering pride in hospital work, reducing working hours, ensuring smooth promotion processes, and enhancing career prospects can all decrease their likelihood of choosing to resign. Absorbing practical nursing management and work experience from other countries will help decrease the intention to resign within this group. PATIENT OR PUBLIC CONTRIBUTION: No patient or public contribution.


Subject(s)
Intensive Care Units , Intention , Job Satisfaction , Nursing Staff, Hospital , Humans , China , Surveys and Questionnaires , Adult , Female , Male , Nursing Staff, Hospital/psychology , Personnel Turnover/statistics & numerical data , Attitude of Health Personnel , Nurses/psychology , Middle Aged
8.
J Infect Dev Ctries ; 18(8): 1233-1240, 2024 Aug 31.
Article in English | MEDLINE | ID: mdl-39288385

ABSTRACT

INTRODUCTION: This study aims to investigate the changing epidemiology and antimicrobial susceptibility of bacteria isolated from cerebrospinal fluid (CSF) in the Shandong region. METHODOLOGY: We conducted a retrospective analysis of bacterial distribution and resistance patterns in CSF samples, utilizing data from the SPARSS network and analyzed with WHONET 5.6 software. RESULTS: A total of 3968 pathogenic bacterial strains were isolated, consisting of 70.6% Gram-positive bacteria, 27.2% Gram-negative bacteria, and 0.2% fungi. The six most commonly detected bacteria were coagulase-negative staphylococcus, Acinetobacter baumannii, Klebsiella pneumoniae, Streptococcus pneumoniae, Escherichia coli, and staphylococcus aureus. Analysis revealed gender and seasonal variations in the distribution of CSF pathogens, with a higher incidence observed in males and during autumn compared to other seasons. The susceptibility profiles of these bacterial species varied significantly, with many exhibiting multidrug resistances. A. baumannii showed a high resistance rate to cephalosporins and carbapenems but was sensitive to tigecycline and polymyxins. For treating multidrug-resistant A. baumannii infections, polymyxin-based combinations with tigecycline or sulbactam are recommended for adults, while tigecycline combined with meropenem is suggested for children. Enterobacteriaceae species were generally sensitive to carbapenems, such as meropenem and other carbapenems that can penetrate the blood-brain barrier can be recommended. Linezolid and vancomycin are the first choice for treating common gram-positive bacterial infections. CONCLUSIONS: The high resistance rates observed among common CSF isolates and their varied distributions across different demographics highlight the necessity for customized treatment strategies.


Subject(s)
Anti-Bacterial Agents , Meningitis, Bacterial , Microbial Sensitivity Tests , Retrospective Studies , Humans , China/epidemiology , Meningitis, Bacterial/microbiology , Meningitis, Bacterial/epidemiology , Meningitis, Bacterial/drug therapy , Meningitis, Bacterial/cerebrospinal fluid , Anti-Bacterial Agents/pharmacology , Anti-Bacterial Agents/therapeutic use , Prevalence , Male , Female , Adult , Child , Gram-Negative Bacteria/drug effects , Gram-Negative Bacteria/isolation & purification , Drug Resistance, Multiple, Bacterial , Middle Aged , Drug Resistance, Bacterial , Child, Preschool , Infant , Adolescent , Young Adult , Gram-Positive Bacteria/drug effects , Gram-Positive Bacteria/isolation & purification , Bacteria/drug effects , Bacteria/isolation & purification , Bacteria/classification
9.
Front Pharmacol ; 15: 1418456, 2024.
Article in English | MEDLINE | ID: mdl-39104395

ABSTRACT

The Ten-Eleven Translocation (TET) family genes are implicated in a wide array of biological functions across various human cancers. Nonetheless, there is a scarcity of studies that comprehensively analyze the correlation between TET family members and the molecular phenotypes and clinical characteristics of different cancers. Leveraging updated public databases and employing several bioinformatics analysis methods, we assessed the expression levels, somatic variations, methylation levels, and prognostic values of TET family genes. Additionally, we explored the association between the expression of TET family genes and pathway activity, tumor microenvironment (TME), stemness score, immune subtype, clinical staging, and drug sensitivity in pan-cancer. Molecular biology and cytology experiments were conducted to validate the potential role of TET3 in tumor progression. Each TET family gene displayed distinct expression patterns across at least ten detected tumors. The frequency of Single Nucleotide Variant (SNV) in TET genes was found to be 91.24%, primarily comprising missense mutation types, with the main types of copy number variant (CNV) being heterozygous amplifications and deletions. TET1 gene exhibited high methylation levels, whereas TET2 and TET3 genes displayed hypomethylation in most cancers, which correlated closely with patient prognosis. Pathway activity analysis revealed the involvement of TET family genes in multiple signaling pathways, including cell cycle, apoptosis, DNA damage response, hormone AR, PI3K/AKT, and RTK. Furthermore, the expression levels of TET family genes were shown to impact the clinical staging of tumor patients, modulate the sensitivity of chemotherapy drugs, and thereby influence patient prognosis by participating in the regulation of the tumor microenvironment, cellular stemness potential, and immune subtype. Notably, TET3 was identified to promote cancer progression across various tumors, and its silencing was found to inhibit tumor malignancy and enhance chemotherapy sensitivity. These findings shed light on the role of TET family genes in cancer progression and offer insights for further research on TET3 as a potential therapeutic target for pan-cancer.

10.
Mol Ther ; 2024 Jul 31.
Article in English | MEDLINE | ID: mdl-39091030

ABSTRACT

Although CRISPR-Cas9 technology is poised to revolutionize the treatment of diseases with underlying genetic mutations, it faces some significant issues limiting clinical entry. They include low-efficiency in vivo systemic delivery and undesired off-target effects. Here, we demonstrate, by modifying Cas9 with phosphorothioate-DNA oligos (PSs), that one can efficiently deliver single and bi-specific CRISPR-Cas9/guide RNA (gRNA) dimers in vitro and in vivo with reduced off-target effects. We show that PS-Cas9/gRNA-mediated gene knockout preserves chimeric antigen receptor T cell viability and expansion in vitro and in vivo. PS-Cas9/gRNA mediates gene perturbation in patient-derived tumor organoids and mouse xenograft tumors, leading to potent tumor antitumor effects. Further, HER2 antibody-PS-Cas9/gRNA conjugate selectively perturbs targeted genes in HER2+ ovarian cancer xenografts in vivo. Moreover, we created bi-specific PS-Cas9 with two gRNAs to target two adjacent sequences of the same gene, leading to efficient targeted gene disruption ex vivo and in vivo with markedly reduced unintended gene perturbation. Thus, the cell-penetrating PS-Cas9/gRNA can achieve efficient systemic delivery and precision in gene disruption.

11.
BMC Infect Dis ; 24(1): 770, 2024 Aug 01.
Article in English | MEDLINE | ID: mdl-39090540

ABSTRACT

BACKGROUND: The GeneXpert MTB/RIF (Xpert) assay is a widely used technology for detecting Mycobacterium tuberculosis (MTB) in clinical samples. However, the study on the failure of the Xpert assay during routine implementation and its potential solutions is limited. METHODS: We retrospectively analyzed the records of unsuccessful tests in the Xpert and the GeneXpert MTB/RIF Ultra (Ultra) assays between April 2017 and April 2021 at the Shanghai Public Health Clinical Center. To further investigate the effect of prolonged preprocessing on clinical sputum, an additional 120 sputum samples were collected for Xpert testing after 15 min, 3 h, and 6 h preprocessing. The analysis was performed by SPSS version 19.0 software. RESULTS: A total of 11,314 test records were analyzed, of which 268 (2.37%) had unsuccessful test results. Among these, 221 (1.95%) were reported as "Error", 43 (0.38%) as "Invalid", and 4 (0.04%) as "No result". The most common clinical specimen for Xpert tests was sputum, accounting for 114 (2.17%) unsuccessful tests. The failure rate of urine specimens was lower than that of sputum (OR = 0.12, 95% CI: 0.02-0.88, χ2 = 6.22, p = 0.021). In contrast, the failure rate of stool specimens was approximately twice as high as that of sputum (OR = 1.93, 95% CI: 1.09-3.40, χ2 = 5.35, p = 0.014). In the prolonged preprocessing experiment, 102 cases (85%) yielded consistent results in Xpert tests. Furthermore, 7 cases (5.83%) detected an increase in MTB load, 8 cases (6.67%) detected a decrease in MTB load, and 3 cases (2.5%) yielded incongruent results in MTB and rifampicin resistance detection. CONCLUSIONS: The primary cause of unsuccessful tests in the Xpert assay was reported as "Error". Despite varying failure rates depending on the samples, the Xpert assay can be applied to extrapulmonary samples. For paucibacillary specimens, retesting the remaining preprocessed mixture should be carefully considered.


Subject(s)
Mycobacterium tuberculosis , Sputum , Humans , Mycobacterium tuberculosis/genetics , Mycobacterium tuberculosis/isolation & purification , Sputum/microbiology , Retrospective Studies , China , Specimen Handling/methods , Molecular Diagnostic Techniques/methods , Tuberculosis/diagnosis , Tuberculosis/microbiology , Rifampin/pharmacology , Tuberculosis, Pulmonary/diagnosis , Tuberculosis, Pulmonary/microbiology , Male , Female
12.
BMC Psychol ; 12(1): 446, 2024 Aug 19.
Article in English | MEDLINE | ID: mdl-39160623

ABSTRACT

BACKGROUND: Type 2 diabetes mellitus is a chronic disease and one of the fastest- growing global health emergencies of the 21st century. The relationships between hope level, social support, disease perception, and self-management behaviors are still unclear. Therefore, this study aimed to create a structural equation model to investigate the underlying mechanisms of self-management behaviors in patients with type 2 diabetes mellitus and provide a theoretical basis for future interventions. METHODS: By using cross-sectional studies and convenience sampling methods. A survey was conducted from June 2023 to April 2024 on 404 patients with type 2 diabetes mellitus at the First and Third Hospitals of Jinzhou Medical University. Data were collected using scales, including the General Information Questionnaire, the Herth Hope Scale, the Social Support Rating Scale, the Brief Disease Perception Questionnaire, and the Diabetes Self-Management Behavior Scale. Data were analyzed using descriptive analysis, Harman's one-way analysis of variance, Pearson's correlation test, structural equation modeling, and the bootstrap method to verify mediating effects. RESULTS: Correlation analyses showed that all four variables were significantly correlated with each other (p < 0.01). Social support had the strongest correlation with self-management behavior (ß = 0.554, p < 0.01), followed by hope level (ß = 0.543, p < 0.01), and disease perception (ß = -0.505, p < 0.01). The structural equation model indicated a strong overall fit (χ2/df = 3.378, GFI = 0.926, CFI = 0.924, IFI = 0.925, TLI = 0.903, RMSEA = 0.077). CONCLUSION: Overall, the chain mediation of social support and disease perception was significant. In developing targeted intervention strategies, future research should prioritize enhancing hope, optimizing social support, and reducing negative perceptions of disease by patients as key areas of focus. At the same time, strengthening self-management abilities and health behaviors in patients with type 2 diabetes should not be neglected.


Subject(s)
Diabetes Mellitus, Type 2 , Hope , Self-Management , Social Support , Humans , Diabetes Mellitus, Type 2/psychology , Diabetes Mellitus, Type 2/therapy , Female , Male , Self-Management/psychology , Self-Management/methods , Middle Aged , Cross-Sectional Studies , China , Aged , Adult , Surveys and Questionnaires , Health Behavior , East Asian People
13.
Support Care Cancer ; 32(9): 608, 2024 Aug 22.
Article in English | MEDLINE | ID: mdl-39172232

ABSTRACT

INTRODUCTION: Baduanjin was also called Eight Brocades (EB), a branch of Qigong exercise, is classified as a mild-to-moderate intensity aerobic exercise. It has been theorized that regular practice of EB can alleviate anxiety and depression in patients undergoing chemotherapy; however, there are currently no comprehensive quantitative reviews on the efficacy of EB for this population. Therefore, this meta-analysis aims to investigate the effects of EB on chemotherapy-treated patients. METHODS: Eight electronic databases were searched from their inception until February 15, 2024, to identify relevant studies. The inclusion and exclusion criteria were applied to filter the retrieved studies. Outcomes were various quantitative assessments. This systematic review was registered in the PROSPERO Registry (registration number CRD42023466630). RESULTS: Nine randomized controlled trials (RCTs) met eligibility criteria (n = 704). The meta-analysis results demonstrated that EB significantly reduced levels of anxiety and depression. Subgroup analysis revealed that the intervention frequency of 1 time/day had a greater effect on the improvement of negative emotions, compared with 2 times/day and 5 times/week. The intervention duration of 4 weeks showed more efficacy in reducing depression scores than 12 weeks or 16 weeks; however, no statistical difference was observed for anxiety scores. CONCLUSION: EB exercise can reduce depression and anxiety symptoms in chemotherapy-treated patients. However, the results should be interpreted with caution as existing methodological limitations. The findings provided insights into the development of public health initiatives to improve the negative emotion among chemotherapy-treated patients by EB exercise.


Subject(s)
Anxiety , Depression , Neoplasms , Qigong , Randomized Controlled Trials as Topic , Humans , Neoplasms/drug therapy , Neoplasms/psychology , Qigong/methods , Depression/etiology , Anxiety/etiology , Antineoplastic Agents/therapeutic use , Antineoplastic Agents/adverse effects , Emotions
14.
Chem Commun (Camb) ; 60(74): 10156-10159, 2024 Sep 12.
Article in English | MEDLINE | ID: mdl-39189692

ABSTRACT

An efficient chalcogenative annulation strategy for constructing functionalized saturated N-heterocycles from unactivated alkenes with dichalcogenides under electrochemical conditions has been presented. This protocol is applicable to mono-, di- or tri-substituted alkenes, providing a straightforward pathway to aziridines, azetidines, pyrrolidines, and piperidines with high regioselectivity. Moreover, the strategy is qualified to realize the oxychalcogenation of alkenes as well.

15.
Adv Sci (Weinh) ; 11(34): e2400741, 2024 Sep.
Article in English | MEDLINE | ID: mdl-38992961

ABSTRACT

Myocardial infarction (MI) triggers a poor ventricular remodeling response, but the underlying mechanisms remain unclear. Here, the authors show that sentrin-specific protease 1 (SENP1) is downregulated in post-MI mice and in patients with severe heart failure. By generating cardiomyocyte-specific SENP1 knockout and overexpression mice to assess cardiac function and ventricular remodeling responses under physiological and pathological conditions. Increased cardiac fibrosis in the cardiomyocyte-specific SENP1 deletion mice, associated with increased fibronectin (Fn) expression and secretion in cardiomyocytes, promotes fibroblast activation in response to myocardial injury. Mechanistically, SENP1 deletion in mouse cardiomyocytes increases heat shock protein 90 alpha family class B member 1 (HSP90ab1) SUMOylation with (STAT3) activation and Fn secretion after ventricular remodeling initiated. Overexpression of SENP1 or mutation of the HSP90ab1 Lys72 ameliorates adverse ventricular remodeling and dysfunction after MI. Taken together, this study identifies SENP1 as a positive regulator of cardiac repair and a potential drug target for the treatment of MI. Inhibition of HSP90ab1 SUMOylation stabilizes STAT3 to inhibit the adverse ventricular remodeling response.


Subject(s)
Cysteine Endopeptidases , Disease Models, Animal , Fibrosis , HSP90 Heat-Shock Proteins , Myocytes, Cardiac , Animals , Myocytes, Cardiac/metabolism , Mice , Cysteine Endopeptidases/metabolism , Cysteine Endopeptidases/genetics , Fibrosis/metabolism , Fibrosis/genetics , HSP90 Heat-Shock Proteins/metabolism , HSP90 Heat-Shock Proteins/genetics , Paracrine Communication/genetics , Sumoylation , Mice, Knockout , Humans , Myocardial Infarction/metabolism , Myocardial Infarction/genetics , Myocardial Infarction/pathology , Ventricular Remodeling/genetics , Ventricular Remodeling/physiology , Male
16.
Pract Lab Med ; 40: e00416, 2024 May.
Article in English | MEDLINE | ID: mdl-38989481

ABSTRACT

Objectives: Rapid antigen test (RAT) and polymerase chain reaction (PCR) using nasopharyngeal (NP) or oropharyngeal (OP) swab specimens are the two main testing techniques used for laboratory diagnosis of influenza in clinical practice. However, performance variations have been observed not only between techniques, but also between different specimens. This study evaluated the differences in performance between specimens and testing techniques to identify the best combination in clinical practice. Methods: Both NP and OP samples from suspected influenza patients collected in the 2023/4-2023/5 Flu-season in Xiamen, China, were tested for RAT and quantitative PCR. The testing performance of the different specimens and testing techniques were recorded and evaluated. Results: Compared to PCR, RAT showed 58.9 % and 10.3 % sensitivity for NP and OP swabs, respectively. The Limit of Detection (LoD) was 28.71 the Median Tissue Culture Infectious Dose (TCID50)/mL. Compared with PCR using NP swabs, PCR with OP swabs showed 89.5 % sensitivity and 95.4 % specificity. Conclusions: There were no significant differences in performance between the specimens when PCR was used to test for influenza. However, a decrease in sensitivity was observed when the RAT was used, regardless of the specimen type. Therefore, to avoid false-negative results, PCR may be a better choice when OP swabs are used as specimens. In contrast, NP swabs should be the recommended specimens for RAT.

17.
Liver Int ; 2024 Jul 22.
Article in English | MEDLINE | ID: mdl-39037259

ABSTRACT

BACKGROUND: Extracellular vesicles (EVs) facilitate cell-cell interactions in the tumour microenvironment. However, standard and efficient methods to isolate tumour tissue-derived EVs are lacking, and their biological functions remain elusive. METHODS: To determine the optimal method for isolating tissue-derived EVs, we compared the characterization and concentration of EVs obtained by three previously reported methods using transmission electron microscopy, nanoparticle tracking analysis, and nanoflow analysis (Nanoflow). Additionally, the differential content of small RNAs, especially tsRNAs, between hepatocellular carcinoma (HCC) and adjacent normal liver tissues (ANLTs)-derived EVs was identified using Arraystar small RNA microarray. The targets of miRNAs and tsRNAs were predicted, and downstream functional analysis was conducted using Gene Ontology, Kyoto Encyclopedia of Genes and Genomes, non-negative matrix factorization and survival prediction analysis. RESULTS: A differential centrifugation-based protocol without cell cultivation (NC protocol) yielded higher EV particles and higher levels of CD9+ and CD63+ EVs compared with other isolation protocols. Interestingly, the NC protocol was also effective for isolating frozen tissue-derived EVs that were indistinguishable from fresh tissue. HCC tissues showed significantly higher EV numbers compared with ANLTs. Furthermore, we identified different types of small RNAs in HCC tissue-derived EVs, forming a unique multidimensional intercellular communication landscape that can differentiate between HCC and ANLTs. ROC analysis further showed that the combination of the top 10 upregulated small RNAs achieved better diagnostic performance (AUC = .950 [.895-1.000]). Importantly, most tsRNAs in HCC tissue-derived EVs were downregulated and mitochondria-derived, mainly involving in lipid-related metabolic reprogramming. CONCLUSION: The NC protocol was optimal for isolating EVs from HCC, especially from frozen tissues. Our study emphasized the different roles of small-RNA in regulating the HCC ecosystem, providing insights into HCC progression and potential therapeutic targets.

18.
Infect Drug Resist ; 17: 3081-3088, 2024.
Article in English | MEDLINE | ID: mdl-39050829

ABSTRACT

Anaerobic bacterial meningitis is a serious infection of the central nervous system (CNS) that leads to severe neurological complications, resulting in high levels of disability and mortality worldwide. However, accurately diagnosing and isolating the responsible pathogens remains challenging due to the difficulty in culturing anaerobic bacteria, as they require harsh anaerobic culture conditions. Anaerobic bacteria have rarely been reported in meningitis, especially in children. This report details the first infant with anaerobic meningitis caused by Prevotella bivia. Additionally, we present a case of infant anaerobic meningitis caused by P. bivia, detected using metagenomics next-generation sequencing (mNGS). Our clinical experience highlights the importance of early identification of Prevotella spp. through mNGS and anaerobic culture, the effectiveness of antimicrobial medications, and the timely implementation of carefully planned precision therapeutic regimens. Furthermore, we have conducted a comprehensive review of 10 cases of Prevotella spp. infection, summarized their clinical and laboratory examination characteristics, and identified their commonalities.

19.
Expert Opin Drug Saf ; : 1-5, 2024 Aug 02.
Article in English | MEDLINE | ID: mdl-39078219

ABSTRACT

BACKGROUND: The objective of this study was to evaluate the reporting associations between Central serous chorioretinopathy (CSCR) and many available drugs using FAERS. RESEARCH DESIGN AND METHODS: FAERS reports from 2004 to 2023 were included in the study. The Medical Dictionary for Regulatory Activities (MedDRA) was used to identify CSCR cases. Reporting odds ratios (RORs) and corresponding 95% confidence intervals (CIs) for the reporting associations between available drugs and CSCR were calculated. A reporting association was considered statistically significant when the lower limit of the 95% CI was > 1.0. RESULTS: There were 1002 reports of 110 drugs with suspected drug-associated CSCR based on the 'primary suspects' role code in the FAERS database found to have statistically significant signals. Among the top 20 ROR drugs, the most frequently reported drugs were dermatological drugs (ATC:D, 210 cases, 64.41%), followed by antitumor agents and immunological agents (ATC:L,77 cases, 23.62%), Systemic Hormonal Preparations, Excl. Sex hormones and Insulins (ATC:H, 19 cases, 5.80%) and sensory organ drugs (ATC:S, 9 cases, 2.76%). The top 3 drugs associated with CSCR were Prednisolone (144 cases, 44.17%), Fluticasone (29 cases, 8.90%), and Methylprednisolone (27 cases, 8.28%). CONCLUSIONS: This is the first real-world study using FAERS database to investigate drug-induced CSCR. Clinicians and pharmacist must keep in mind CSCR is a serious ocular complication associated with glucocorticoids, tyrosine kinase receptor inhibitor, and other drugs that can cause CSCR.

20.
Front Nutr ; 11: 1400116, 2024.
Article in English | MEDLINE | ID: mdl-38946785

ABSTRACT

Background: Previous observational studies have indicated a potential association between the gut microbiota and multiple myeloma (MM). However, the relationship between the gut microbiota and MM remains unclear. This study aimed to ascertain the existence of a causal link between the gut microbiota and MM. Methods: To investigate the potential causal relationship between gut microbiota and MM, a two-sample Mendelian randomization (MR) analysis was conducted. Exposure data was obtained from the MiBioGen consortium, which provided genetic variants associated with 211 bacterial traits. MM outcome data was obtained from the FinnGen consortium. The selection of Single nucleotide polymorphisms estimates was performed through meta-analysis using inverse-variance weighting, and sensitivity analyses were conducted using weighted median, MR Egger, Simple mode, and MR-PRESSO. Results: The results of the study demonstrated a significant positive correlation between the genus Eubacterium ruminantium group and the risk of MM (OR 1.71, 95% CI 1.21 to 2.39). Conversely, the genus: Dorea (OR 0.46, 95% CI 0.24 to 0.86), Coprococcus1 (OR 0.47, 95% CI 0.22 to 1.00), RuminococcaceaeUCG014 (OR 0.57, 95% CI 0.33 to 0.99), Eubacterium rectale group (OR 0.37, 95% CI 0.18 to 0.77), and order: Victivallales (OR 0.62, 95% CI 0.41-0.94), class: Lentisphaeria (OR 0.62, 95% CI 0.41 to 0.94), exhibited a negative association with MM. The inverse variance weighting analysis provided additional support for these findings. Conclusion: This study represents an inaugural exploration of MR to investigate the connections between gut microbiota and MM, thereby suggesting potential significance for the prevention and treatment of MM.

SELECTION OF CITATIONS
SEARCH DETAIL