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1.
Anal Methods ; 2024 Jun 10.
Artículo en Inglés | MEDLINE | ID: mdl-38855900

RESUMEN

Prothioconazole and its metabolite are considered a potential threat to human health and environmental safety. Thus, the development of a sensitive and rapid detection method for prothioconazole is crucial to ensure the safety of agricultural products. In this study, a new hapten of prothioconazole was designed and synthesized, and a selective polyclonal antibody with high affinity against prothioconazole was produced, which was obtained from immunized New Zealand white rabbits. Based on the polyclonal antibody, an indirect competitive enzyme-linked immunosorbent assay (ic-ELISA) and indirect competitive chemiluminescence enzyme immunoassay (ic-CLEIA) were developed for detecting prothioconazole pesticides. Under optimized experimental conditions, the limit of quantification (LOQ) values for ic-CLEIA and ic-ELISA were 1.8 and 10.7 ng mL-1, respectively. The results demonstrated that the sensitivity (LOQ) achieved by ic-CLEIA was more than five times higher compared to that obtained with ic-ELISA. In addition, the recoveries obtained by adding standard prothioconazole to wheat grain, soybean, and pond water samples were in the range of 81.9 to 104.7% for ic-ELISA and 89.0 to 118.0% for ic-CLEIA.

2.
J Agric Food Chem ; 2024 Jun 11.
Artículo en Inglés | MEDLINE | ID: mdl-38861684

RESUMEN

This study confirmed a field population of American sloughgrass (Beckmannia syzigachne (Steud.) Fernald) that developed simultaneously high levels of resistance (resistance index >10) to three divergent modes of action herbicides: fenoxaprop-P-ethyl, mesosulfuron-methyl, and isoproturon. The resistance phenotype observed in this population was not attributed to target-site alterations; rather, the resistant plants exhibited a significant increase in the activity of cytochrome P450s (P450s) and enhanced metabolism rates for all three herbicides. RNA sequencing revealed significant upregulation of two P450s, CYP709B1 and CYP704C1, in the resistant plants both before and after herbicide treatments. Molecular docking predicted that the homology models of these P450s should exhibit a binding affinity for a range of herbicides. The heterologous expression of the identified P450s in yeast cells indicated improved growth in the presence of all three of the aforementioned herbicides. Collectively, the increased expression of CYP709B1 and CYP704C1 likely contributed to the P450s-mediated enhanced metabolism, thereby conferring multiple herbicide resistance in B. syzigachne.

3.
Aging Dis ; 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38739930

RESUMEN

Vascular calcification (VC) is the ectopic deposition of calcium-containing apatite within vascular walls, exhibiting a high prevalence in older adults, and those with diabetes or chronic kidney disease. VC is a subclinical cardiovascular risk trait that increases mortality and functional deterioration. However, effective treatments for VC remain largely unavailable despite multiple attempts. Part of this therapeutic nihilism results from the failure to appreciate the diversity of VC as a pathological complex, with unforeseeable variations in morphology, risk associates, and anatomical and molecular pathogenesis, affecting clinical management strategies. VC should not be considered a homogeneous pathology because accumulating evidence refutes its conceptual and content uniformity. Here, we summarize the pathophysiological sources of VC heterogeneity from the intersecting pathways and networks of cellular, subcellular, and molecular crosstalk. Part of these pathological connections are synergistic or mutually antagonistic. We then introduce clinical implications related to the VC heterogeneity concept. Even within the same individual, a specific artery may exhibit the strongest tendency for calcification compared with other arteries. The prognostic value of VC may only be detectable with a detailed characterization of calcification morphology and features. VC heterogeneity is also evident, as VC risk factors vary between different arterial segments and layers. Therefore, diagnostic and screening strategies for VC may be improved based on VC heterogeneity, including the use of radiomics. Finally, pursuing a homogeneous treatment strategy is discouraged and we suggest a more rational approach by diversifying the treatment spectrum. This may greatly benefit subsequent efforts to identify effective VC therapeutics.

4.
J Agric Food Chem ; 72(21): 12014-12028, 2024 May 29.
Artículo en Inglés | MEDLINE | ID: mdl-38748759

RESUMEN

Alopecurus aequalis Sobol. is a predominant grass weed in Chinese winter wheat fields, posing a substantial threat to crop production owing to its escalating herbicide resistance. This study documented the initial instance of an A. aequalis population (AHFT-3) manifesting resistance to multiple herbicides targeting four distinct sites: acetyl-CoA carboxylase (ACCase), acetolactate synthase, photosystem II, and 1-deoxy-d-xylulose-5-phosphate synthase. AHFT-3 carried an Asp-to-Gly mutation at codon 2078 of ACCase, with no mutations in the remaining three herbicide target genes, and exhibited no overexpression of any target gene. Compared with the susceptible population AHFY-3, AHFT-3 metabolized mesosulfuron-methyl, isoproturon, and bixlozone faster. The inhibition and comparison of herbicide-detoxifying enzyme activities indicated the participation of cytochrome P450s in the resistance to all four herbicides, with glutathione S-transferases specifically linked to mesosulfuron-methyl. Three CYP72As and a Tau class glutathione S-transferase, markedly upregulated in resistant plants, potentially played pivotal roles in the multiple-herbicide-resistance phenotype.


Asunto(s)
Acetil-CoA Carboxilasa , Resistencia a los Herbicidas , Herbicidas , Proteínas de Plantas , Poaceae , Resistencia a los Herbicidas/genética , Herbicidas/farmacología , Herbicidas/metabolismo , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Acetil-CoA Carboxilasa/genética , Acetil-CoA Carboxilasa/metabolismo , Poaceae/genética , Poaceae/metabolismo , Poaceae/efectos de los fármacos , Acetolactato Sintasa/genética , Acetolactato Sintasa/metabolismo , Sistema Enzimático del Citocromo P-450/genética , Sistema Enzimático del Citocromo P-450/metabolismo , Mutación , Malezas/efectos de los fármacos , Malezas/genética , Malezas/metabolismo
5.
Sci Rep ; 14(1): 11504, 2024 05 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769360

RESUMEN

Pressure drifting is a troublesome error in invasive coronary function tests. This study aimed to evaluate the relationship between prolonged and short-time pressure equalizations in pressure drifting. Pressure drifting was defined as the pressure gradient between the mean pressure of the distal wire sensor (Pd) and aortic pressure (Pa) when the wire was withdrawn to the tip of the guiding catheter. Significant drifts 1 and 2 were defined as the absolute values of pressure gradients > 2 and > 3 mmHg, respectively. A logistic regression model was used to evaluate the associations between prolonged pressure equalization and each pressure drifting. The prolonged pressure equalization strategy was associated with a lower incidence of drift 1 than the short-time pressure equalization strategy (6.84% vs. 16.92%, p < 0.05). However, no statistical differences were found in the incidence of drift 2 between the prolonged and short-time pressure equalization strategies (4.27% vs. 7.69%, p = 0.34). In the multivariable regression model, only the prolonged pressure equalization strategy predicted a lower incidence of pressure drift 1. In conclusion, the prolonged pressure equalization strategy was associated with a lower incidence of significant pressure drifting with more stringent thresholds than the short-time pressure equalization strategy.


Asunto(s)
Cateterismo Cardíaco , Humanos , Masculino , Femenino , Anciano , Persona de Mediana Edad , Cateterismo Cardíaco/métodos , Presión , Presión Sanguínea/fisiología
6.
Biomed Pharmacother ; 176: 116802, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38795643

RESUMEN

Oxidative stress plays a key role in chronic kidney disease (CKD) development and progression, inducing kidney cell damage, inflammation, and fibrosis. However, effective therapeutic interventions to slow down CKD advancement are currently lacking. The multifaceted pharmacological effects of molecular hydrogen (H2) have made it a promising therapeutic avenue. H2 is capable of capturing harmful •OH and ONOO- while maintaining the crucial reactive oxygen species (ROS) involved in cellular signaling. The NRF2-KEAP1 system, which manages cell redox balance, could be used to treat CKD. H2 activates this pathway, fortifying antioxidant defenses and scavenging ROS to counteract oxidative stress. H2 can improve NRF2 signaling by using the Wnt/ß-catenin pathway and indirectly activate NRF2-KEAP1 in mitochondria. Additionally, H2 modulates NF-κB activity by regulating cellular redox status, inhibiting MAPK pathways, and maintaining Trx levels. Treatment with H2 also attenuates HIF signaling by neutralizing ROS while indirectly bolstering HIF-1α function. Furthermore, H2 affects FOXO factors and enhances the activity of antioxidant enzymes. Despite the encouraging results of bench studies, clinical trials are still limited and require further investigation. The focus of this review is on hydrogen's role in treating renal diseases, with a specific focus on oxidative stress and redox signaling regulation, and it discusses its potential clinical applications.

7.
Int Immunopharmacol ; 135: 112285, 2024 Jun 30.
Artículo en Inglés | MEDLINE | ID: mdl-38762922

RESUMEN

Inflammatory bowel disease (IBD) is a chronic and recurrent gastrointestinal inflammation regulated by intricate mechanisms. Recently, prebiotics is considered as promising nutritional strategy for the prevention and treatment of IBD. Prevotella histicola (P. histicola), an emerging probiotic, possesses apparently anti-inflammatory bioactivity. However, the role and underlying mechanism of P. histicola on IBD remain unclear. Hence, we probe into the effect of P. histicola on dextran sulfate sodium (DSS)-induced colitis and clarified the potential mechanism. Our results revealed that DSS-induced colonic inflammatory response and damaged epithelial barrier in mice were attenuated by oral administration of P. histicola. Moreover, supplementary P. histicola significantly enriched short-chain fatty acid (SCFA)-producing bacteria (Lactobacillus, and Bacillus) and reduced pathogenic bacteria (Erysipelotrichaceae, Clostridium, Bacteroides) in DSS-induced colitis. Notably, In DSS-treated mice, endoplasmic reticulum stress (ERS) was persistently activated in colonic tissue. Conversely, P. histicola gavage suppressed expansion of endoplasmic reticulum, downregulated PERK-ATF4-CHOP and IRE1α-JNK pathway. In vitro, the P. histicola supernatant eliminated LPS-induced higher production of pro-inflammatory cytokines regulated by NF-κB and impairment of epithelial barrier by inhibiting IRE1α-JNK signaling in Caco-2 cell. In summary, our study indicated that P. histicola mitigated DSS-induced chronic colitis via inhibiting IRE1α-JNK pathway and NF-κB signaling. These findings provide the new insights into the promotion of gut homeostasis and the application potential of P. histicola as a prebiotic for IBD in the future.


Asunto(s)
Colitis , Sulfato de Dextran , Estrés del Retículo Endoplásmico , Endorribonucleasas , Ratones Endogámicos C57BL , FN-kappa B , Prevotella , Proteínas Serina-Treonina Quinasas , Animales , Colitis/inducido químicamente , Colitis/microbiología , Colitis/patología , Estrés del Retículo Endoplásmico/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , FN-kappa B/metabolismo , Ratones , Endorribonucleasas/metabolismo , Humanos , Probióticos/uso terapéutico , Transducción de Señal/efectos de los fármacos , Masculino , Colon/patología , Colon/microbiología , Colon/efectos de los fármacos , Colon/inmunología , Microbioma Gastrointestinal/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Modelos Animales de Enfermedad
8.
RSC Adv ; 14(17): 11914-11920, 2024 Apr 10.
Artículo en Inglés | MEDLINE | ID: mdl-38623300

RESUMEN

Interfacial Lewis acid-base pairs are commonly found in ZrO2-supported metal catalysts due to the facile generation of oxygen vacancies of ZrO2. These pairs have been reported to play a crucial role in olefin hydroesterification, especially in the absence of acid promoters and ligands. In this study, a series of ZrO2-supported Ru catalysts with ruthenium(iii) chloride and ruthenium(iii) acetylacetonate as precursors were prepared for the styrene hydroesterification. The catalysts were thoroughly characterized by TPR, TEM, EPR, XPS, and FTIR. The Ru precursors significantly influenced the size and electronic properties of Ru clusters, albeit having minimal impact on oxygen vacancies. Mechanistic studies of styrene hydroesterification over ZrO2-supported Ru catalysts revealed that the carbon monoxide insertion followed the hydrogen transfer step to activated styrene. Higher activity is exhibited over ZrO2-supported Ru catalysts prepared with ruthenium(iii) chloride as a precursor, attributed to the lower adsorption strength of CO over Ru clusters, as evidenced by FTIR and DFT calculations.

9.
J Behav Addict ; 2024 Apr 26.
Artículo en Inglés | MEDLINE | ID: mdl-38669079

RESUMEN

Background and aims: In 2021, China implemented a policy to prevent adolescents from excessive online gaming, with the goal of encouraging healthier leisure activities. Methods: Three months after this policy was implemented, we conducted a study involving 430 Chinese adolescents who regularly played online games for over two hours daily before the policy. We collected their responses to the restriction, including their compliance with the policy, engagement in undesirable alternative behaviors (e.g., watching short videos), and engagement in desirable alternative behaviors (e.g., playing sports). We also collected data on individual factors, parental technology interference, and feelings of restriction to use as predictors for behaviors, including those related to violating the restriction or watching short videos. Results: A small percentage of heavy gamers violated the restriction by renting others' game accounts (3%) or using a family member's identity (14%), while 59% of the sample shifted to watching short videos. Heavy gamers who lived in rural areas, spent more time on online games prior to the policy, did not feel restricted from playing online games, and experienced parental technology interference were more likely to violate the restriction. Females or those lacking stable hobbies were more inclined to watch short videos. Conclusions: Although the policy restricted heavy gaming, it has also led to increased short video use. Policymakers could explore alternative approaches, such as developing infrastructure that supports outdoor leisure activities in rural areas, encouraging parents to model responsible technology use behaviors, and guiding adolescents to cultivate positive hobbies in their leisure time.

10.
Sci Rep ; 14(1): 7645, 2024 04 01.
Artículo en Inglés | MEDLINE | ID: mdl-38561361

RESUMEN

Remimazolam, a novel intravenous anesthetic, has been proven to be safe and efficacious in the gastroscopy setting among the elderly. However, reports comparing the effectiveness and safety of using equivalent doses of remimazolam with propofol have not been seen. The aim of this study was to compare the sedation efficacy and safety of the 95% effective doses (ED95) of remimazolam versus propofol combined with sufentanil in the gastroscopy setting among the elderly. In the first step of this two-step study, a modified up-and-down method was used to calculate the ED95 of remimazolam and propofol when combined with 0.1 µg/kg sufentanil in inhibiting body movement of elderly patients undergoing gastroscopy. In the second step, ED95 of both agents calculated in the first step were administered, endpoints of efficacy, safety, and incidence of adverse events were compared. A total of 46 individuals completed the first step. The ED95 of remimazolam was 0.163 mg/kg (95% CI 0.160-0.170 mg/kg), and that of propofol was 1.042 mg/kg (95% CI 1.007-1.112 mg/kg). In the second step, 240 patients completed the trial. The anesthetic effective rates of the remimazolam group and the propofol group were 78% and 83%, respectively, with no statistical difference (P = 0.312). Patients in the remimazolam group had more stable circulatory functions (P < 0.0001) and a lower incidence of pain on injection (3.3% vs. 19.5%, P < 0.0001). The incidence of hypotension was low in the remimazolam versus propofol group (15.6% vs. 39.0%, P < 0.0001). Overall adverse event was low in the remimazolam versus propofol group (21.3% vs. 62.7%, P < 0.0001).In this study, we found that when anesthesia was administered to elderly gastroscopy patients based on 95% effective doses of remimazolam and propofol, remimazolam was as effective as propofol, but was safer with a lower incidence of adverse events.Study registration: Chinese Clinical Trial Registry, ChiCTR2000034234. Registered 29/06/2020, https://www.chictr.org.cn .


Asunto(s)
Anestesia , Propofol , Anciano , Humanos , Benzodiazepinas , Gastroscopía , Propofol/efectos adversos , Sufentanilo
11.
Pestic Biochem Physiol ; 200: 105826, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38582590

RESUMEN

Acetyl-CoA carboxylase (ACCase)-inhibiting herbicides are among the most commonly used herbicides to control grassy weeds, especially Leptochloa chinensis, in rice fields across China. Herein, we collected a suspected resistant (R) population of L. chinensis (HFLJ16) from Lujiang county in Anhui Province. Whole plant dose response tests showed that, compared with the susceptible (S) population, the R population showed high resistance to cyhalofop-butyl (22-fold) and displayed cross-resistance to metamifop (9.7-fold), fenoxaprop-P-ethyl (18.7-fold), quizalofop-P-ethyl (7.6-fold), clodinafop-propargyl (12-fold) and clethodim (8.4-fold). We detected an amino acid substitution (Cys-2088-Arg) in the ACCase of resistant L. chinensis. However, ACCase gene expression levels were not significantly different (P > 0.05) between R plants and S plants, without or with cyhalofop-butyl treatment. Furthermore, pretreatment with piperonyl butoxide (PBO, a cytochrome P450 monooxygenase (CYP450) inhibitor) or 4-chloro-7-nitrobenzoxadiazole (NBD-Cl, a glutathione-S-transferase (GST) inhibitor), inhibited the resistance of the R population to cyhalofop-butyl significantly (by approximately 60% and 26%, respectively). Liquid chromatography tandem mass spectrometry analysis showed that R plants metabolized cyhalofop-butyl and cyhalofop acid (its metabolite) significantly faster than S plants. Three CYP450 genes, one GST gene, and two ABC transporter genes were induced by cyhalofop-butyl and were overexpressed in the R population. Overall, GST-associated detoxification, CYP450 enhancement, and target-site gene mutation are responsible for the resistance of L. chinensis to cyhalofop-butyl.


Asunto(s)
4-Cloro-7-nitrobenzofurazano , Acetil-CoA Carboxilasa , Butanos , Herbicidas , Nitrilos , Oxazoles , Propionatos , Acetil-CoA Carboxilasa/metabolismo , Proteínas de Plantas/genética , Poaceae/genética , Poaceae/metabolismo , Herbicidas/farmacología , Sistema Enzimático del Citocromo P-450/genética , Mutación , Resistencia a los Herbicidas/genética
12.
Pestic Biochem Physiol ; 201: 105856, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38685238

RESUMEN

Plutella xylostella is an important pest showing resistance to various chemical pesticides, development of botanical pesticides is an effective strategy to resolve above problem and decrease utilization of chemical pesticides. Previous study showed that 2,3-dimethyl-6-(1-hydroxy)-pyrazine has significant repellent activity to P. xylostella adult which mainly effect to the olfactory system, however the molecular targets and mechanism are still unclear. Based on the RNA-Seq and RT-qPCR data, eight ORs (Odorant receptor) in P. xylostella were selected as candidate targets response to repellent activity of 2,3-dimethyl-6-(1-hydroxy)-pyrazine. Here, most of the ORs in P. xylostella were clustered into three branches, which showed similar functions such as recognition, feeding, and oviposition. PxylOR29, PxylOR31, and PxylOR46 were identified as the potential molecular targets based on the results of repellent activity and EAG response tests to the adults which have been injected with dsRNA, respectively. Additionally, the three ORs were higher expressed in antenna of P. xylostella, followed by those in the head segment. Furthermore, it was found that the bindings between these three ORs and 2,3-dimethyl-6-(1-hydroxy)-pyrazine mainly depend on the hydrophobic effect of active cavities, and the binding to PxylOR31 was more stabler and easier with an energy of -16.34 kcal/mol, together with the π-π T-shaped interaction at PHE195 site. These findings pave the way for the complete understanding of pyrazine repellent mechanisms.


Asunto(s)
Repelentes de Insectos , Mariposas Nocturnas , Pirazinas , Receptores Odorantes , Animales , Receptores Odorantes/metabolismo , Receptores Odorantes/genética , Pirazinas/farmacología , Repelentes de Insectos/farmacología , Mariposas Nocturnas/efectos de los fármacos , Mariposas Nocturnas/metabolismo , Proteínas de Insectos/metabolismo , Proteínas de Insectos/genética
13.
Biol Methods Protoc ; 9(1): bpae011, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38486874

RESUMEN

The establishment of high sensitive detection method for various pathogenic microorganisms remains constantly concerned. In the present study, multi-probe strategy was first systematically investigated followed by establishing a highly sensitive TaqMan real-time fluorescent quantitative PCR (qPCR) method for detecting African swine fever virus (ASFV). Briefly, four probes based on the B646L gene of ASFV were designed and the effects of different combinations of the probes in a single TaqMan qPCR assay on the detection sensitivity were investigated. As less as 0.5-5 copies/µl of the ASFV gene was detected by the established TaqMan qPCR assay. Furthermore, plasmid harboring the B646L in water samples could be concentrated 1000 times by ultrafiltration to enable a highly sensitive detection of trace viral nucleic acids. Moreover, no cross-reactivity was observed with other common clinical swine viruses such as PCV2, PCV3, PCV4, PEDV, PDCoV, CSFV, PRRSV, and PRV. When detecting 173 clinical porcine serum samples, the coincidence rate between the developed method and WOAH (World Organization of Animal Health) recommended method was 100%. This study might provide an integrated strategy to achieve higher detection sensitivity of trace pathogenic microorganisms and applicably sensitive TaqMan-based qPCR assays.

14.
Afr J Reprod Health ; 28(2): 43-54, 2024 Feb 28.
Artículo en Inglés | MEDLINE | ID: mdl-38425153

RESUMEN

Polycystic ovary syndrome (PCOS), as an endocrine and metabolic disorder, affects approximately 6% -20% of women of childbearing age. This study aims to assess the therapeutic effects of Metformin combined with vitamin D in PCOS patients. Eight databases were searched to obtain randomized controlled trials, both domestically and internationally, on the effects of Metformin combined with vitamin D in patients with PCOS. Data analysis was performed using RevMan 5.3 software. Nine studies were ultimately included in this meta-analysis. Six studies reported the homeostatic model assessment for insulin resistance of the test group and the control group, which was significantly lower (SMD: -0.23; 95% Cl: -0.42,-0.04; P<0.05) than the control group, body mass index (BMI) (SMD: -1.86; 95% Cl: -2.77,-0.96; P<0.01), Serum 25 (OH) D (SMD: 14.28; 95% Cl: 12.26,16.29; P<0.01), testosterone (SMD: -0.11; 95% Cl: -0.15,-0.07; P<0.01) and regulated menstrual cycles (OR: 1.27; 95% Cl: 0.99,1.63; P=0.063). Our meta-analysis of nine trials demonstrates significant reductions in insulin resistance, BMI, and testosterone levels, along with increased serum vitamin D levels and improved menstrual cycle regulation after Metformin and vitamin D treatment. These findings suggest the potential of this combined therapy in managing the multifaceted aspects of PCOS.


Le syndrome des ovaires polykystiques (SOPK), en tant que trouble endocrinien et métabolique, touche environ 6 à 20 % des femmes en âge de procréer. Cette étude vise à évaluer les effets thérapeutiques de la metformine associée à la vitamine D chez les patients atteints du SOPK. Huit bases de données ont été consultées pour obtenir des essais contrôlés randomisés, tant au niveau national qu'international, sur les effets de la metformine associée à la vitamine D chez les patients atteints du SOPK. L'analyse des données a été réalisée à l'aide du logiciel RevMan 5.3. Neuf études ont finalement été incluses dans cette méta-analyse. Six études ont rapporté l'évaluation du modèle homéostatique pour la résistance à l'insuline du groupe test et du groupe témoin, qui était significativement inférieure (DMS : -0,23 ; IC à 95 % : -0,42, -0,04 ; P <0,05) par rapport au groupe témoin, la masse corporelle indice (IMC) (DMS : -1,86 ; Cl 95 % : -2,77, -0,96 ; P<0,01), Sérum 25 (OH) D (SMD : 14,28 ; Cl 95 % : 12,26,16,29 ; P<0,01), testostérone (DMS : -0,11 ; Cl à 95 % : -0,15, -0,07 ; P<0,01) et cycles menstruels régulés (OR : 1,27 ; Cl à 95 % : 0,99, 1,63 ; P=0,063). Notre méta-analyse de neuf essais démontre des réductions significatives de la résistance à l'insuline, de l'IMC et des taux de testostérone, ainsi qu'une augmentation des taux sériques de vitamine D et une amélioration de la régulation du cycle menstruel après un traitement à la metformine et à la vitamine D. Ces résultats suggèrent le potentiel de cette thérapie combinée dans la gestion des aspects multiformes du SOPK.


Asunto(s)
Metformina , Síndrome del Ovario Poliquístico , Vitamina D , Femenino , Humanos , Hipoglucemiantes/uso terapéutico , Resistencia a la Insulina/fisiología , Metformina/uso terapéutico , Síndrome del Ovario Poliquístico/tratamiento farmacológico , Testosterona/metabolismo , Vitamina D/uso terapéutico
15.
J Med Chem ; 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38511243

RESUMEN

There is an urgent requirement to acquire a comprehensive comprehension of novel therapeutic targets for prostate cancer to facilitate the development of medications with innovative mechanisms. In this study, we identified gambogic acid (GBA) as a specific pyroptosis inducer in prostatic cancer cells. By using a thermal proteome profiling (TPP) strategy, we revealed that GBA induces pyroptosis by directly targeting the canopy FGF signaling regulator (CNPY3), which was previously considered "undruggable". Moreover, through the utilization of the APEX2-based proximity labeling method, we found that GBA recruited delactatease SIRT1, resulting in the elimination of lysine lactylation (Kla) on CNPY3. Of note, SIRT1-mediated delactylation influenced the cellular localization of CNPY3 to promote lysosome rupture for triggering pyroptosis. Taken together, our study identified CNPY3 as a distinctive cellular target for pyroptosis induction and its potential application in prostate cancer therapy.

16.
Biochim Biophys Acta Mol Basis Dis ; 1870(4): 167104, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38437993

RESUMEN

Ischemic stroke is the main cause of death and disability, and microglia play a crucial role in the pathophysiology of hypoxic ischemic brain injury. We found that SENP3 is highly expressed in the early stages of ischemic stroke in both in vivo and in vitro mouse models, and may be related to the deSUMOylation of the key kinase MKK7 in the TLR4/p-JNK signaling pathway. Knocking down SENP3 can inhibit the deSUMOylation of MKK7, thereby inhibiting the activation of the TLR4/p-JNK signaling pathway in an in vitro stroke model. Proteomic analysis showed that SENP3 undergoes phosphorylation at the T429 site after ischemic stroke. Computer simulation predictions show a significant enhancement of the interaction between pT429-SENP3 and MKK7, which has been confirmed through experiments on the interaction of biological macromolecules (SPR). The mitochondrial metabolic abnormalities caused by energy abnormalities in the early stages of stroke provide a good explanation for the phosphorylation of SENP3. Therefore, we used the mitochondrial complex inhibitor TTFA to reverse demonstrate that the phosphorylation of SENP3 comes from the large amount of adenosine triphosphate produced by mitochondrial abnormal metabolism caused by early oxygen glucose deficiency. Finally, proteomic analysis indicates that a significant amount of oxidative phosphorylation does occur in the early stages of stroke. In summary, targeted regulation of SENP3 phosphorylation to affect the deSUMOylation of MKK7 may inhibit secondary inflammation in ischemic stroke.


Asunto(s)
Accidente Cerebrovascular Isquémico , Ratones , Animales , Simulación por Computador , Proteómica , Receptor Toll-Like 4 , Cisteína Endopeptidasas/metabolismo , Inflamación/metabolismo
17.
Medicine (Baltimore) ; 103(10): e37391, 2024 Mar 08.
Artículo en Inglés | MEDLINE | ID: mdl-38457587

RESUMEN

The coronavirus disease 2019 (COVID-19), a dual threat to public physical and mental health, prompted an investigation into the psychological well-being of residents in low- to medium-risk areas of China during the initial stages of the pandemic. We administered WeChat-based questionnaire surveys and employed chi-square tests and multiple logistic regression to analyze correlations between residents' age, gender, education, symptoms, COVID-19 close contact history, information sources, and anxiety, depression, and attitudes toward lockdown measures. We received 10,433 valid questionnaires, revealing 26% anxiety and 19.5% depression. Support for lockdown measures reached 98.2%. Factors such as female gender, self-diagnosed pneumonia symptoms, close contact history, and higher education levels increased anxiety risk. Having a doctorate posed a severe anxiety risk, at 4.5 times (P = .019, 95% CI 1.29-15.73). Older age acted as a protective factor, reducing severe anxiety risk to 0.98 and 0.22 times (P < .001, 95% CI 0.14-0.34). Females with a master degree or below and those receiving COVID-19 information from multiple channels faced higher depression risk. Pneumonia symptoms were a risk for all anxiety and depression degrees. Attitudes toward lockdown measures had no significant impact on psychological status, nor did any of the analyzed factors affect residents' overall attitude toward lockdown. Our findings underscore the need for increased psychological counseling, particularly for young females with lower educational backgrounds or self-suspected infection symptoms, to mitigate mild to moderate anxiety and depression in future epidemics or pandemics. The public, especially those of working age with doctorates or higher education, bears the highest risk of severe anxiety. Lockdown measures enjoy strong support in low- to medium-risk areas of China.


Asunto(s)
COVID-19 , Humanos , Femenino , COVID-19/epidemiología , COVID-19/prevención & control , SARS-CoV-2 , Depresión/epidemiología , Depresión/psicología , Estrés Psicológico/epidemiología , Control de Enfermedades Transmisibles , Ansiedad/epidemiología , Ansiedad/psicología , Encuestas y Cuestionarios , Pandemias/prevención & control , China/epidemiología
18.
J Agric Food Chem ; 72(7): 3363-3373, 2024 Feb 21.
Artículo en Inglés | MEDLINE | ID: mdl-38324778

RESUMEN

Cyantraniliprole is a novel insecticide recently introduced for rice pest control that may cause potential threats to the red swamp crayfish (Procambarus clarkii) in rice-crayfish coculture systems. In this study, we investigated the acute toxicity of cyantraniliprole against P. clarkii with a LC50 value of 149.77 mg/L (96 h), first. Some abnormal behaviors of P. clarkii treated with 125 mg/L cyantraniliprole, including incunabular hyperexcitability, imbalance, inactivity, and increased excretion were observed. Moreover, it was observed that exposure to 5 mg/L cyantraniliprole for 14 days resulted in histopathological alterations in abdominal muscle, gills, hepatopancreas, and intestines. Furthermore, exposure to 0.05 and 5 mg/L cyantraniliprole induced increased activities of several oxidative stress-related enzymes, which was verified by the upregulation of related genes. Additionally, dysregulation of the intestinal microbiota was determined via 16S rRNA sequencing. These results will provide the basis for the utilization of cyantraniliprole in the fields of rice-crayfish integrated system.


Asunto(s)
Microbioma Gastrointestinal , Oryza , Pirazoles , ortoaminobenzoatos , Animales , Astacoidea/genética , ARN Ribosómico 16S , Estrés Oxidativo
19.
Behav Sci (Basel) ; 14(2)2024 Feb 08.
Artículo en Inglés | MEDLINE | ID: mdl-38392478

RESUMEN

Effective interpersonal emotion regulation (IER) strategies have been found to be meaningful predictors for positive psychological functioning. The Difficulties in Interpersonal Regulation of Emotions Scale (DIRE) is a measure developed to assess maladaptive IER strategies. This study aimed to examine the psychometric properties of the Chinese version of DIRE using two college student samples (Sample 1: n = 296; Sample 2: n = 419). The two-factor structure of DIRE (venting and excessive reassurance-seeking) was confirmed through an exploratory structure equation modeling approach. Our results demonstrated that the Chinese version of DIRE exhibits a similar factor structure (in both samples) as the original DIRE. Measurement invariance across gender and samples was also achieved. Latent mean analyses demonstrated that females more frequently reported excessive reassurance-seeking (in both samples) and venting (in Sample 1) than males. Furthermore, venting and excessive reassurance-seeking were significantly related to intrapersonal emotion regulation and well-being indicators. Although in Chinese culture DIRE performs somewhat differently from the original DIRE, the current findings suggest that DIRE is a reliable and valid scale with which to measure the IER strategies in Chinese culture and the use of this measure in clinical practice may allow for an accurate assessment of emotion regulation deficits in clients from other diverse cultures.

20.
Br J Pharmacol ; 181(12): 1857-1873, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38382564

RESUMEN

BACKGROUND AND PURPOSE: The holotoxin A1, isolated from Apostichopus japonicus, exhibits potent antifungal activities, but the mechanism and efficacy against candidiasis are unclear. In this study we have studied the antifungal effects and mechanism of holotoxin A1 against Candida albicans and in murine oropharyngeal and intra-abdominal candidiasis. EXPERIMENTAL APPROACH: The antifungal effect of holotoxin A1 against C. albicans was tested in vitro. To explore the antifungal mechanism of holotoxin A1, the transcriptome, ROS levels, and mitochondrial function of C. albicans was evaluated. Effectiveness and systematic toxicity of holotoxin A1 in vivo was assessed in the oropharyngeal and intra-abdominal candidiasis models in mice. KEY RESULTS: Holotoxin A1 was a potent fungicide against C. albicans SC5314, clinical strains and drug-resistant strains. Holotoxin A1 inhibited oxidative phosphorylation and induced oxidative damage by increasing intracellular accumulation of ROS in C. albicans. Holotoxin A1 induced dysfunction of mitochondria by depolarizing the mitochondrial membrane potential and reducing the production of ATP. Holotoxin A1 directly inhibited the enzymatic activity of mitochondrial complex I and antagonized with the rotenone, an inhibitor of complex I, against C. albicans. Meanwhile, the complex I subunit NDH51 null mutants showed a decreased susceptibility to holotoxin A1. Furthermore, holotoxin A1 significantly reduced fungal burden and infections with no significant systemic toxicity in oropharyngeal and intra-abdominal candidiasis in murine models. CONCLUSION AND IMPLICATIONS: Holotoxin A1 is a promising candidate for the development of novel antifungal agents against both oropharyngeal and intra-abdominal candidiasis, especially when caused by drug-resistant strains.


Asunto(s)
Antifúngicos , Candida albicans , Estrés Oxidativo , Especies Reactivas de Oxígeno , Animales , Femenino , Ratones , Antifúngicos/farmacología , Candida albicans/efectos de los fármacos , Candidiasis/tratamiento farmacológico , Candidiasis/microbiología , Candidiasis Bucal/tratamiento farmacológico , Candidiasis Bucal/microbiología , Infecciones Intraabdominales/tratamiento farmacológico , Infecciones Intraabdominales/microbiología , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Ratones Endogámicos BALB C , Pruebas de Sensibilidad Microbiana , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Estrés Oxidativo/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Stichopus/microbiología
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