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1.
Anal Chem ; 2024 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-39484690

RESUMO

The sustainable identification and efficient degradation of some recessive and seriously toxic pollutants are important issues in practical applications. Herein, a portable platform (EAl/ACN/Ag) constructed by growing AgNPs in situ in the cavities of the alkalized carbon nitride (ACN) coated on the etched Al sheet (EAl) is achieved. Interestingly, on the constructed EAl/ACN/Ag substrate irradiated by light for 3 min, a Raman inactive leuco-malachite green (LMG: a highly toxic and environmentally persistent pollutant that is difficult to be found due to being colorless) can be sensitively and selectively detected by surface-enhanced Raman scattering spectroscopy (SERS). Results demonstrate that the abundant •O2-, •OH, and h+ active species produced by irradiation of the EAl/ACN/Ag are responsible for the sensitive and selective SERS detection of the Raman-inactive LMG. The green and sustainable initiation in the sensitive SERS detection of LMG is greatly different from those by the traditional chemical process. The limit of detection of LMG can reach 8.99 × 10-13 mol·L-1, which is superior to some other methods for LMG detection in real samples. In addition, the EAl/ACN/Ag substrate displays excellent photocatalytic activity for LMG molecules. The research will provide a new and green way for the sensitive detection and efficient removal of some recessive and toxic pollutants in food fields and environmental analyses.

2.
Biochemistry ; 2024 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-39499622

RESUMO

Fungal ribosomally synthesized and post-translationally modified peptides (RiPPs) are a vital class of natural products known for their biological activities including anticancer, antitubulin, antinematode, and immunosuppressant properties. These bioactive fungal RiPPs play key roles in chemical ecology and have a significant therapeutic potential. Their structural diversity, which arises from intricate post-translational modifications of precursor peptides, is particularly remarkable. Despite their biological and ecological importance, the discovery of fungal RiPPs has been historically challenging and only a limited number have been identified. To date, known fungal RiPPs are primarily grouped into three groups: cycloamanides and borosins from basidiomycetes and dikaritins from ascomycetes. Recent advancements in bioinformatics have revealed the vast untapped potential of fungi to produce RiPPs, offering new opportunities for their discovery. This review highlights recent progress in fungal RiPP biosynthesis and genome-guided discovery strategies. We propose that combining the knowledge of fungal RiPP biosynthetic pathways with advanced gene-editing technologies and bioinformatic tools will significantly accelerate the discovery of novel bioactive fungal RiPPs.

3.
Int J Antimicrob Agents ; : 107371, 2024 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-39486466

RESUMO

Skin injuries and infections are an inevitable part of daily human life, particularly with chronic wounds, becoming an increasing socioeconomic burden. In treating skin infections and promoting wound healing, bioactive peptides may hold significant potential, particularly those possessing antimicrobial and anti-inflammatory properties. However, obtaining these peptides solely through traditional wet laboratory experiments is costly and time-consuming, and peptides identified by current computer-assisted predictive models largely lack validation of their effects via wet laboratory experiments. Consequently, this study aimed to integrate computer-assisted methods and traditional wet laboratory experiments to identify anti-inflammatory and antimicrobial peptides. We developed a computer-assisted mining pipeline to screen potential peptides from the epitopes of the major histocompatibility complex class II (MHC-II). The peptide AIMP1 was identified, with the ability to physically damage Escherichia coli by increasing bacterial cell membrane permeability and with the ability to inhibit inflammation by binding to endotoxin-lipopolysaccharide. Additionally, in an LPS-induced inflammation animal model, AIMP1 slightly increased levels of proinflammatory cytokines (TNF-α, IL-1ß, and IL-6), and in a skin wound infection animal model, AIMP1 effectively accelerated healing, reduced levels of these pro-inflammatory cytokines, and showed no acute hepatotoxicity or nephrotoxicity. In conclusion, this study not only developed a computer-assisted mining pipeline for identifying anti-inflammatory and antimicrobial peptides but also successfully pinpointed the peptide AIMP1, demonstrating its therapeutic potential for skin injury treatment.

4.
J Dairy Sci ; 2024 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-39414017

RESUMO

Hybrids between closely related but genetically incompatible species are often inviable or sterile. Cattle-yak, an interspecific hybrid of yak and cattle, exhibits male-specific sterility, which limits the fixation of its desired traits and prevents genetic improvement in yak through crossbreeding. Transcriptome profiles of testicular tissues have been generated in cattle, yak, and cattle-yak; however, the genetic variations underlying differential gene expression associated with hybrid sterility have yet to be elucidated. We detected differences in the cellular composition and gene expression of testes from yak and cattle-yak at 3 mo of age, 10 mo of age and adulthood. Histological analysis revealed that the most advanced germ cells were gonocytes (prospermatogonia) at 3 mo and spermatocytes at 10 mo. Complete spermatogenesis occurred in the seminiferous tubules of adult yak, whereas only spermatogonia and a limited number of spermatocytes were detected in the testis of adult cattle-yak. Transcriptome analysis revealed 180, 6310, and 6112 differentially expressed genes (DEGs) in yak and cattle-yak at each stage, respectively. Next, we examined the spermatogenic cell types in the backcross generation (BC1) and detected the appearance of round spermatids, indicating the partial recovery of spermatogenesis in these animals. Compared with those in cattle-yak, 272 DEGs were identified in the testes of BC1 animals. Notably, we discovered that the expression of X chromosome-linked (X-linked) genes was upregulated in the testis of cattle-yak compared with yak, suggesting a possible abnormality in the process of meiotic sex chromosome inactivation (MSCI) in hybrid animals. We next screened DEGs harboring structural variations (SVs) and identified a list of SV genes associated with spermatogonial development, meiotic recombination, and double-strand break (DSB) repair. Furthermore, we found that the SV genes ESCO2 (establishment of sister chromatid cohesion N-acetyltransferase 2) and BRDT (bromodomain testis associated) may be involved in meiotic arrest of cattle-yak spermatocytes. Overall, our research provides a valuable database for identifying structural variant loci that contribute to hybrid sterility.

5.
Cardiol Res ; 15(5): 358-368, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39420974

RESUMO

Background: The H2FPEF score, a convenient tool developed for diagnosing heart failure with preserved ejection fraction (HFpEF), exhibited useful prognostic utility in HFpEF. However, the applicability and the prognostic value of the H2FPEF score in Chinese HFpEF patients have yet to be fully confirmed. The study aimed to evaluate the effect of modified H2FPEF score on the prognosis of Chinese HFpEF patients. Methods: In this retrospective study, we calculated the H2FPEF scores by body mass index (BMI) ≥ 25 kg/m2 and 30 kg/m2 respectively, for 497 consecutive HFpEF patients in China. Subjects were divided into low- (0 - 3 points), intermediate- (4 - 6 points), and high-score (7 - 9 points) groups. The primary and secondary endpoints were heart failure (HF)-related events and acute coronary syndrome (ACS), respectively. Cox proportional hazard models were applied to calculate hazard ratios (HRs). Receiver operating characteristic (ROC) curves and areas under the curve (AUC) were used to evaluate the prediction of the H2FPEF score for adverse outcomes. Results: Over a mean follow-up of 40.46 ± 6.52 months, the primary and secondary endpoints occurred in 168 patients (33.8%) and 97 patients (19.5%), respectively. By the definition of obesity as BMI ≥ 25 kg/m2, a higher incidence of HF-related events and ACS was observed among those with a higher modified H2FPEF score. The modified H2FPEF significantly predicted HF-related events (AUC: 0.723; 95% confidence interval (CI): 0.676 - 0.770; P < 0.001) and ACS (AUC: 0.670; 95% CI: 0.608 - 0.731; P < 0.014) with higher power than the H2FPEF score calculated by BMI ≥ 30 kg/m2. The cutoff of the modified H2FPEF score was 6.5 for detecting HF-related events and ACS. Conclusions: The modified H2FPEF score, using BMI ≥ 25 kg/m2 to define obesity, could more effectively predict the occurrence of subsequent cardiovascular events in Chinese HFpEF patients. The modified H2FPEF score above 6.5 is a risk factor for adverse cardiovascular events in HFpEF patients.

6.
Echocardiography ; 41(10): e15928, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39367766

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is strongly linked to the incidence and mortality of cardiovascular diseases (CVDs), with left ventricular myocardial damage being the most prevalent. This study aimed to assess left ventricle (LV) dysfunction using three-dimensional speckle tracking imaging (3D-STI) in CKD patients. METHODS: A total of 110 CKD patients and 55 healthy volunteers underwent echocardiography. CKD patients were divided into CKD1 group and CKD2 group based on the estimated glomerular filtration rate (eGFR). Assessing cardiac function via two-dimensional speckle tracking echocardiography (2D-STE) and three-dimensional speckle tracking echocardiography (3D-STE) parameters, with strain presented in absolute terms. Collecting and comparing clinical and echocardiographic parameters from three groups, assessing 3D-STI's value in evaluating LV functional impairment in CKD patients via correlation and receiver operating characteristic (ROC) curve analyses, and identifying risk factors for CKD progression to end-stage renal disease (ESRD) through univariate and multivariate analyses. RESULTS: In CKD2 group, 2D-left ventricular ejection fraction (LVEF), 3D-LVEF, 2D left ventricular global longitudinal strain (2D-LVGLS), 3D-LVGLS, and 3D-left ventricular global circumferential peak strain (LVGCS) significantly worsen compared to the control and CKD1 groups, with statistically significant distinctions between the latter two (all p < 0.05). The absolute value of 3D-LVGLS shows a robust correlation with N-terminal pro-B-type natriuretic peptide (NT-proBNP) and serum creatinine (Scr) (r = -0.598, -0.649, both p < 0.001). ROC curve analysis indicates higher diagnostic efficacy of 3D-LVGLS and 3D-LVGCS for LV systolic function than 2D-LVGLS. Univariate and multivariate analyses reveal an independent association of 3D-LVGLS with the progression to ESRD in CKD. CONCLUSION: 3D-LVGLS and 3D-LVGCS effectively detect LV dysfunction in CKD patients. Specifically, 3D-LVGLS demonstrates a robust correlation with NT-proBNP and Scr and is independently linked to CKD progressing to ESRD.


Assuntos
Ecocardiografia Tridimensional , Insuficiência Renal Crônica , Disfunção Ventricular Esquerda , Humanos , Masculino , Feminino , Ecocardiografia Tridimensional/métodos , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/fisiopatologia , Pessoa de Meia-Idade , Disfunção Ventricular Esquerda/fisiopatologia , Disfunção Ventricular Esquerda/diagnóstico por imagem , Disfunção Ventricular Esquerda/etiologia , Disfunção Ventricular Esquerda/complicações , Ventrículos do Coração/diagnóstico por imagem , Ventrículos do Coração/fisiopatologia , Adulto , Reprodutibilidade dos Testes
7.
Adv Sci (Weinh) ; : e2408093, 2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-39373392

RESUMO

In situ disc regeneration is a meticulously orchestrated process, which involves cell recruitment, proliferation and differentiation within a local inflammatory niche. Thus far, it remains a challenge to establish a multi-staged regulatory framework for coordinating these cellular events, therefore leading to unsatisfactory outcome. This study constructs a super paramagnetically-responsive cellular gel, incorporating superparamagnetic iron oxide nanoparticles (SPIONs) and aptamer-modified palladium-hydrogen nanozymes (PdH-Apt) into a double-network polyacrylamide/hyaluronic acid (PAAm/HA) hydrogel. The Aptamer DB67 within magnetic hydrogel (Mag-gel) showed a high affinity for disialoganglioside (GD2), a specific membrane ligand of nucleus pulposus stem cells (NPSCs), to precisely recruit them to the injury site. The Mag-gel exhibits remarkable sensitivity to a magnetic field (MF), which exerts tunable micro/nano-scale forces on recruited NPSCs and triggers cytoskeletal remodeling, consequently boosting cell expansion in the early stage. By altering the parameters of MF, the mechanical cues within the hydrogel facilitates differentiation of NPSCs into nucleus pulposus cells to restore disc structure in the later stage. Furthermore, the PdH nanozymes within the Mag-gel mitigate the harsh inflammatory microenvironment, favoring cell survival and disc regeneration. This study presents a remote and multi-staged strategy for chronologically regulating endogenous stem cell fate, supporting disc regeneration without invasive procedures.

8.
Sci Total Environ ; 955: 176796, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39389142

RESUMO

The prevalence of mental health issues in the US has significantly risen over the past decade, and it is presumably linked to an energy burden issue that has recently gained attention as a critical social determinant of mental health. Utilizing extensive nationwide datasets at the census tract, we found that the census tract level energy burden is positively associated with two key mental health indicators even after accounting for living, housing, and sociodemographic characteristics: the prevalence of frequent mental distress and physician-diagnosed depression, across all US urban areas. We also observe that these associations are consistent across various climate regions. The findings highlight that energy burden has a detrimental impact on mental health, and that it should be e considered a significant social determinant of health in future studies. Lastly, our study advocates for national policies to achieve energy justice and address disparities in mental health.

9.
Front Cardiovasc Med ; 11: 1401609, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39416435

RESUMO

Background: Cardiac rupture (CR) after acute myocardial infarction (AMI) is a fatal mechanical complication. The early identification of factors related to CR in high-risk cases may reduce mortality. The purpose of our study was to discover relevant risk factors for CR after AMI and in-hospital mortality from CR. Methods: In this study, we enrolled 1,699 AMI cases from October 2013 to May 2020. A total of 51 cases were diagnosed with CR. Clinical diagnostic information was recorded and analyzed retrospectively. We randomly matched these cases with AMI patients without CR in a 1:4 ratio. Univariate and multivariate logistic regression and stratifying analysis were used to identify risk factors for CR. Univariate and multivariate Cox regression hazard analysis and stratifying analysis were used to assess predictors of in-hospital mortality from CR. Results: The incidence of CR after AMI was 3.0% and in-hospital mortality was approximately 57%. Multivariate logistic regression analysis identified that white blood cell count, neutrophil percentage, anterior myocardial infarction, a Killip class of >II, and albumin level were independently associated with CR (p < 0.05). Stratifying analysis showed that age, systolic blood pressure, and bicarbonate were independent risk factors for female CR (p < 0.05) but not male CR. Triglyceride and cardiac troponin I were independent risk factors for male CR (p < 0.05) but not female CR. Anterior myocardial infarction, a Killip class of >II, and neutrophil percentage were independent risk factors for male and female CR (p < 0.05). Multivariate Cox regression analysis showed that the time from symptom to CR and the site of CR were independent predictors for in-hospital mortality from CR (p < 0.05). Stratification analysis indicated that risk factors did not differ based on gender, but platelet counts were predictors for in-hospital mortality in female and male CR. Conclusion: Low albumin, a high white blood cell count, neutrophil percentage, anterior myocardial infarction, and a Killip class of >II were independent and significant predictors for CR. However, risk factors are different in male and female CR. The time from symptom to CR, the site of CR, and platelet counts were independent predictors for in-hospital mortality from CR. These may be helpful in the early and accurate identification of high-risk patients with CR and the assessment of prognosis. In addition, gender differences should be considered.

10.
World J Psychiatry ; 14(10): 1484-1494, 2024 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-39474382

RESUMO

BACKGROUND: Interoception dysfunction has an important impact on the onset and development of major depressive disorder (MDD). Social support serves as a protective factor against MDD, and sociability also plays a significant role in this condition. These interconnected constructs-social support and sociability-play pivotal roles in MDD. However, no research on the mechanisms underlying the associations between social support and sociability, particularly the potential role of interoception, have been reported. AIM: To investigate the mediating effect of interoception between social support and social ability and to explore the independent role of social support in sociability. METHODS: The participants included 292 patients with MDD and 257 healthy controls (HCs). The patient health questionnaire 9, the multidimensional assessment of interoception awareness, version 2 (MAIA-2), the social support rating scale (SSRS), and the Texas social behavior inventory (TSBI) were used to assess depression, interoception, social support, and sociability, respectively. A mediation analysis model for the eight dimensions of interoception (noticing, not distracting, not worrying, attention regulation, emotional awareness, self-regulation, body listening, and trust), social support, and sociability were established to evaluate the mediating effects. RESULTS: A partial correlation analysis of eight dimensions of the MAIA-2, SSRS, and TSBI scores, with demographic data as control variables, revealed pairwise correlations between the SSRS score and both the MAIA-2 score and TSBI score. In the major depression (MD) group, the SSRS score had a positive direct effect on the TSBI score, while the scores for body listening, emotional awareness, self-regulation, and trust in the MAIA-2C had indirect effects on the TSBI score. In the HC group, the SSRS score had a positive direct effect on the TSBI score, and the scores for attention regulation, emotional awareness, self-regulation, and trust in the MAIA-2C had indirect effects on the TSBI score. The proportion of mediators in the MD group was lower than that in the HC group. CONCLUSION: Interoceptive awareness is a mediating factor in the association between social support and sociability in both HCs and depressed patients. Training in interoceptive awareness might not only help improve emotional regulation in depressed patients but also enhance their social skills and support networks.

11.
Microbiol Spectr ; : e0026524, 2024 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-39382284

RESUMO

Antibiotic resistance poses a significant public health threat worldwide. The rise in antibiotic resistance and the sharp decline in effective antibiotics necessitate the development of innovative antibacterial agents. Based on the central symmetric structure of glycine-serine-glycine, combined with tryptophan and arginine, we designed a range of antimicrobial peptides (AMPs) that exhibited broad-spectrum antibacterial activity. Notably, AMP W5 demonstrated a rapid and effective sterilization against methicillin-resistant Staphylococcus aureus (MRSA), displaying both a minimum inhibitory concentration and a minimum bactericidal concentration of 8 µM. Mechanistic studies revealed that AMP W5 killed bacterial cells by disrupting the cytoplasmic membrane integrity, triggering leakage of cell contents. AMP W5 also exhibited excellent biocompatibility in both in vitro and in vivo safety evaluations. AMP W5 treatment significantly reduced skin bacterial load in our murine skin infection model. In conclusion, we designed a novel centrosymmetric AMP representing a promising medical alternative to conventional antibiotics for treating MRSA infections. IMPORTANCE: Increasing antibiotic resistance and the paucity of effective antibiotics necessitate innovative antibacterial agents. Methicillin-resistant Staphylococcus aureus (MRSA) is a major pathogen causing bacterial infections with high incidence and mortality rates, showing increasing resistance to clinical drugs. Antimicrobial peptides (AMPs) exhibit significant potential as alternatives to traditional antibiotics. This study designed a novel series of AMPs, characterized by a glycine-serine-glycine-centered symmetrical structure, and our results indicated that AMP W5 exhibited a rapid and effective bactericidal effect against MRSA. AMP W5 also demonstrated excellent biocompatibility and a bactericidal mechanism that disrupted membrane integrity, leading to leakage of cellular contents. The notable reduction in skin bacterial load observed in mouse models reinforced the clinical applicability of AMP W5. This study provides a promising solution for addressing the increasing threat of antibiotic-resistant bacteria and heralds new prospects for clinical applications.

13.
Spectrochim Acta A Mol Biomol Spectrosc ; 325: 125119, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39276468

RESUMO

The aptamers functionalized orange-emission carbon dots (OCDs) and green-emission carbon dots (GCDs) had dual-emission peaks with single excitation. Tungsten disulfide nanosheets (WS2 NSs)-triggered fluorescence quenching achieved the ratiometric fluorescence determination of Escherichia coli O157:H7 (E. coli O157:H7) and Staphylococcus aureus (S. aureus) with wide ranges of 18-1.8 × 106 and 37-3.7 × 107 CFU/mL and low detection limits of 8 and 20 CFU/mL, respectively. The results in real sample with recoveries of 90-101 % and RSD < 4.12 % were no significant difference from standard plate counting method. Meanwhile, the dual-color CDs were further adopted in the smartphone-assisted hydrogel platform and achieved speedy, sensitive, portable and real-time determination of E. coli O157:H7 and S. aureus in real samples. This work has not only developed ratiometric fluorescence detection and constructed a portable hydrogel platform, but also provided a unique strategy in developing a time-efficient and easy-to-use portable device in food safety monitoring.

14.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 41(10): 1271-1276, 2024 Oct 10.
Artigo em Chinês | MEDLINE | ID: mdl-39344626

RESUMO

Pyroptosis is a novel mode for programmed cell death discovered and confirmed in recent years. The Gasdermins (GSDMs) family is a key effector molecule mediating pyroptosis. As an important cause of extensive inflammatory damage and side effects of conventional chemotherapy drugs, anomalous pyroptosis has also been associated with hearing loss, tumor, and disorders of the immune system. The GSDME protein, encoded by the GSDME (DFNA5) gene, belongs to the GSDMs family and is a key factor mediating pyroptosis. Gain-of-function variants of the GSDME gene can lead to GSDME-related hearing loss, which shows an autosomal dominant inheritance. This article has reviewed the role of GSDME-mediated pyroptosis in the pathogenesis of GSDME-related hearing loss, with an aim to provide insights into the treatment of GSDME-related hearing loss.


Assuntos
Perda Auditiva , Piroptose , Piroptose/genética , Humanos , Perda Auditiva/genética , Animais , Gasderminas
15.
Food Funct ; 15(19): 10179-10189, 2024 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-39301672

RESUMO

Green tea polyphenols (GTP), an important phytochemical in the daily human diet, bind to various cellular receptors and exert anti-inflammatory and antioxidant benefits. The environmental contaminant tetrabromobisphenol A (TBBPA) enters the digestive system through multiple pathways, resulting in oxidative stress (OS), gastroenteritis, and mucosal injury. The aim of this study was to explore the molecular mechanisms of TBBPA-induced gastritis in mice treated with GTP in vivo and in an in vitro model. The results showed that exposure to TBBPA increased reactive oxygen species (ROS) levels, activated oxidative stress (OS) induced endoplasmic reticulum stress (ERS), and the expression of endoplasmic reticulum stress-related factors (e.g., GRP78, PERK, IRE-1, ATF-6, etc.) increased. The inflammatory pathway NF-κB was activated, and the pro-inflammatory factors TNF-α, IL-1ß, and IL-6 increased, while triggering a cascade reaction mediated by caspase-3. However, the addition of GTP could inhibit OS, restore the balance of endoplasmic reticulum homeostasis, and improve the inflammatory infiltration and apoptosis of gastric mucosal epithelial cells. Therefore, GTP alleviated ERS, reduced inflammation and apoptosis, and restored the gastric mucosal barrier by alleviating TBBPA-induced OS in mouse gastric tissues and GES-1 cells. This provides basic information for exploring the antioxidant mechanism of GTP and further investigating the toxic effects of TBBPA on mouse gastric mucosa.


Assuntos
Fator 6 Ativador da Transcrição , Apoptose , Chaperona BiP do Retículo Endoplasmático , Gastrite , Bifenil Polibromatos , Polifenóis , Espécies Reativas de Oxigênio , Chá , Animais , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Polifenóis/farmacologia , Apoptose/efeitos dos fármacos , Chá/química , Gastrite/induzido quimicamente , Gastrite/tratamento farmacológico , Gastrite/metabolismo , Fator 6 Ativador da Transcrição/metabolismo , Masculino , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , eIF-2 Quinase/metabolismo , eIF-2 Quinase/genética , Estresse Oxidativo/efeitos dos fármacos , Modelos Animais de Doenças , Humanos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo
16.
Adv Med Sci ; 69(2): 474-483, 2024 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-39326736

RESUMO

PURPOSE: Vascular smooth muscle cell (VSMC) phenotype switch and dysfunctions have been reported to participate in aortic dissection (AD) progression. This study was aimed to investigate the role of angiopoietin-like 4 (ANGPTL4) in regulating VSMCs phenotype switch. MATERIALS AND METHODS: Key genes were analyzed in AD using public datasets, and it was found that the central differential gene ANGPTL4 was up-regulated in AD. The KEGG signaling pathway annotation was performed to validate the associated pathways, and the expression of ANGPTL4 was verified using multiple datasets and clinical samples. Furthermore, the specific functions of ANGPTL4 on platelet-derived growth factor-BB (PDGF-BB)-treated human aortic smooth muscle cell (HASMC) phenotypes were investigated. The dynamic effects of ANGPTL4 and core signaling antagonists on HASMC phenotypes were examined. RESULTS: Hub gene ANGPTL4 was significantly up-regulated in AD. ANGPTL4 was linked to the PI3K/Akt signaling, angiogenesis, and neovascularization and remodeling. ANGPTL4 overexpression further enhanced PDGF-BB effects on HASMC phenotypes, including promoted cell viability and migration, decreased contractile VSMC markers α-SMA and SM22α, elevated ECM degradation markers MMP-2 and MMP-9, and promoted phosphorylation of PI3K and Akt. ANGPTL4 knockdown partially abolished PDGF-BB-induced contractile/synthetic VSMCs imbalance and HASMC dysfunctions. Furthermore, in ANGPTL4-overexpressing HASMCs pre-treated with PDGF-BB, the PI3K/Akt signaling inhibitor LY294002 also partially eliminated the effects caused by the PDGF-BB treatment and ANGPTL4 overexpression. CONCLUSIONS: ANGPTL4 is significantly up-regulated in AD. ANGPTL4 overexpression further enhanced PDGF-BB effects on HASMC phenotype switch and dysfunctions, which might be involved in the PI3K/Akt signaling.

17.
Mikrochim Acta ; 191(10): 575, 2024 09 05.
Artigo em Inglês | MEDLINE | ID: mdl-39235626

RESUMO

Based on the peroxidase activity of Cu-hemin metal-organic framework (Cu-hemin MOF) nanozyme, a colorimetric enzyme-linked immunosensor was developed for the detection of furazolidone (FZD). Cu-hemin MOF is a bimetallic nanozyme that exhibited a stronger catalytic effect compared with single-metal organic framework nanoenzymes. Cu-hemin-MOF catalyzes hydrogen peroxide (H2O2) to produce hydroxyl radicals (•OH), which oxidizes the chromogenic substrate 3,3',5,5'-tetramethylbenzidine (TMB) to blue oxidized TMB (oxTMB). The absorbance change is at 650 nm. The content of AOZ in animal food can be quickly and accurately determined by changes in absorbance. The linear range of the colorimetric biosensor for detecting FZD was 0.01 ~ 62.52 ng/mL, and the limit of detection was as low as 0.01 ng/mL. The recovery of spikes samples was in the range 94.2-108.0 % and reproducibility was less than 4.8%. In addition, the cross-reaction rate was less than 0.1% when detecting other metabolites except AOZ, indicating that the sensor has good applicability and specificity. This study not only provides a better understanding of the relationship between the dispersion of nanoenzymes and enzyme-like activity but also offers a general method for detecting antibiotics using the nanoenzyme colorimetric method.


Assuntos
Colorimetria , Cobre , Furazolidona , Ferro , Limite de Detecção , Estruturas Metalorgânicas , Colorimetria/métodos , Cobre/química , Furazolidona/análise , Furazolidona/química , Estruturas Metalorgânicas/química , Ferro/química , Benzidinas/química , Peróxido de Hidrogênio/química , Animais , Técnicas Biossensoriais/métodos , Imunoensaio/métodos , Catálise
18.
Clin Oral Investig ; 28(10): 522, 2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39264455

RESUMO

OBJECTIVES: This study aimed to explore the causal link between the gut microbiota and periodontitis, and to delineate and quantify the intermediary role of immune cells, so as to provide new insights into the pathogenesis, prevention and treatment of periodontitis. MATERIALS AND METHODS: We employed a two-sample Mendelian randomization (MR) approach to analyze the genetic predictors of gut microbiota composition (covering 412 gut microbiota taxa and functions) and periodontitis (involving 4,784 cases and 272,252 controls) derived from genome-wide association study (GWAS) datasets. A subsequent two-step MR analysis was conducted to evaluate the extent to which immune cell traits (encompassing 731 immune cell characteristics) mediate the influence of gut microbiota on periodontitis risk. RESULTS: Our analysis implicated nine gut microbiota taxa as causal factors in periodontitis susceptibility (p < 0.05). Notably, the Genus Roseburia was identified as exerting a protective effect against periodontitis, partially mediated through the upregulation of CD86 expression on granulocytes, with an 8.15% mediation effect observed. CONCLUSIONS: Our findings establish a causal relationship between the gut microbiota and periodontitis, highlighting the protective role of Roseburia against this condition. A notable proportion of this protective effect is mediated via the upregulation of CD86 on granulocytes. CLINICAL RELEVANCE: It can provide new ideas for the pathogenesis, prevention and treatment for periodontitis through exploring the causal link between the gut microbiota and periodontitis, and describing and quantifying the intermediary role of immune cells.


Assuntos
Antígeno B7-2 , Microbioma Gastrointestinal , Estudo de Associação Genômica Ampla , Granulócitos , Periodontite , Humanos , Periodontite/microbiologia , Periodontite/imunologia , Granulócitos/imunologia , Análise da Randomização Mendeliana
19.
Mikrochim Acta ; 191(9): 515, 2024 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-39105818

RESUMO

A smartphone-assisted portable dual-mode immunoassay was constructed based on curcumin nanoparticles (CNPs) and carbon dots (CDs) for gentamicin (GEN) detection. CNPs were labeled with goat anti-mouse IgG (Ab2) to create a conjugation that coupled dual signals to concentrations of GEN antigens. CNPs were introduced to pH 7.4 water and showed insignificant color and optical responses. When exposed to the high pH environment, the structure of CNPs changed and color and optical properties were restored. Because of the inner filter effect (IFE) between CNPs and CDs, the fluorescence of CNPs at 550 nm quenched the fluorescence of CDs at 450 nm. Colorimetry and ratiometric fluorescence (F550 nm/F450 nm) dual-mode immunoassay linearly correlated with GEN ranged from 10-4 to 100 µg/mL with a detection limit (LOD) of 8.98 × 10-5 µg/mL and 4.66 × 10-5 µg/mL, respectively. This work supplied a portable, sensitive, and specific platform to detect GEN.


Assuntos
Carbono , Curcumina , Gentamicinas , Limite de Detecção , Nanopartículas , Pontos Quânticos , Smartphone , Curcumina/química , Imunoensaio/métodos , Carbono/química , Gentamicinas/análise , Gentamicinas/imunologia , Gentamicinas/química , Pontos Quânticos/química , Nanopartículas/química , Animais , Camundongos
20.
Complement Ther Med ; 85: 103077, 2024 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-39181170

RESUMO

OBJECTIVES: To analyze the methodology, evidence, recommendations, quality, and implementation of traditional Chinese patent medicine (CPM) guidelines. METHODS: We retrieved clinical application guidelines of CPM published from 2019 to 2022. Independent screening and data extraction were performed by two evaluators. The basic information about the guidelines, including evidence and recommendations, were extracted and statistically analyzed. Quality and implementation were evaluated using the Implementation Evaluation Tool and Appraisal of Guidelines for Research & Evaluation (AGREE) II. RESULTS: In total, 29 guidelines were analyzed, including 262 recommendations and 2308 references. All the CPM guidelines followed the principle of "evidence as a core, consensus as a supplement, and experience as a reference" and the methods provided by WHO Handbook. An average of 89 references were cited in each guideline and 8 in each recommendation. Randomized controlled trials and systematic reviews constituted 89 % and 0.9 %, respectively, of all references. Low or very low-quality evidence characterized 74.5 % and weak recommendations characterized 83.6 %. Of all recommendations, 13.7 % were based on expert consensus, and 9.5 % of strong recommendations were based on low or very low-quality evidence. The AGREE II scores for each domain were: scope and purpose (79.63 %) and editorial independence (79.27 %), followed by clarity of presentation (72.59 %), stakeholder involvement (69.99 %), rigor of development (53.97 %) and applicability (5.11 %). The implementation quality of most guidelines was either high (44.8 %) or moderate (55.2 %). CONCLUSIONS: The results for CPM guidelines were impressive in terms of methodology, quality, and implementation. However, confidence in CPM recommendations was downgraded by low quality of evidence.


Assuntos
Medicina Tradicional Chinesa , Guias de Prática Clínica como Assunto , Humanos , China , Medicamentos de Ervas Chinesas/uso terapêutico , Medicamentos sem Prescrição/uso terapêutico
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