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1.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 55(3): 662-670, 2024 May 20.
Artículo en Chino | MEDLINE | ID: mdl-38948267

RESUMEN

Objective: To establish a universally applicable logistic risk prediction model for diabetes mellitus type 2 (T2DM) in the middle-aged and elderly populations based on the results of a Meta-analysis, and to validate and confirm the efficacy of the model using the follow-up data of medical check-ups of National Basic Public Health Service. Methods: Cohort studies evaluating T2DM risks were identified in Chinese and English databases. The logistic model utilized Meta-combined effect values such as the odds ratio (OR) to derive ß, the partial regression coefficient, of the logistic model. The Meta-combined incidence rate of T2DM was used to obtain the parameter α of the logistic model. Validation of the predictive performance of the model was conducted with the follow-up data of medical checkups of National Basic Public Health Service. The follow-up data came from a community health center in Chengdu and were collected between 2017 and 2022 from 7602 individuals who did not have T2DM at their baseline medical checkups done at the community health center. This community health center was located in an urban-rural fringe area with a large population of middle-aged and elderly people. Results: A total of 40 cohort studies were included and 10 items covered in the medical checkups of National Basic Public Health Service were identified in the Meta-analysis as statistically significant risk factors for T2DM, including age, central obesity, smoking, physical inactivity, impaired fasting glucose, a reduced level of high-density lipoprotein cholesterol (HDL-C), hypertension, body mass index (BMI), triglyceride glucose (TYG) index, and a family history of diabetes, with the OR values and 95% confidence interval (CI) being 1.04 (1.03, 1.05), 1.55 (1.29, 1.88), 1.36 (1.11, 1.66), 1.26 (1.07, 1.49), 3.93 (2.94, 5.24), 1.14 (1.06, 1.23), 1.47 (1.34, 1.61), 1.11 (1.05, 1.18), 2.15 (1.75, 2.62), and 1.66 (1.55, 1.78), respectively, and the combined ß values being 0.039, 0.438, 0.307, 0.231, 1.369, 0.131, 0.385, 0.104, 0.765, and 0.507, respectively. A total of 37 studies reported the incidence rate, with the combined incidence being 0.08 (0.07, 0.09) and the parameter α being -2.442 for the logistic model. The logistic risk prediction model constructed based on Meta-analysis was externally validated with the data of 7602 individuals who had medical checkups and were followed up for at least once. External validation results showed that the predictive model had an area under curve (AUC) of 0.794 (0.771, 0.816), accuracy of 74.5%, sensitivity of 71.0%, and specificity of 74.7% in the 7602 individuals. Conclusion: The T2DM risk prediction model based on Meta-analysis has good predictive performance and can be used as a practical tool for T2DM risk prediction in middle-aged and elderly populations.


Asunto(s)
Diabetes Mellitus Tipo 2 , Humanos , Diabetes Mellitus Tipo 2/epidemiología , Persona de Mediana Edad , Anciano , Factores de Riesgo , Modelos Logísticos , Femenino , Masculino , China/epidemiología , Estudios de Cohortes , Salud Pública , Incidencia
2.
Plant J ; 2024 Jun 23.
Artículo en Inglés | MEDLINE | ID: mdl-38923085

RESUMEN

Cotton is a globally cultivated crop, producing 87% of the natural fiber used in the global textile industry. The pigment glands, unique to cotton and its relatives, serve as a defense structure against pests and pathogens. However, the molecular mechanism underlying gland formation and the specific role of pigment glands in cotton's pest defense are still not well understood. In this study, we cloned a gland-related transcription factor GhHAM and generated the GhHAM knockout mutant using CRISPR/Cas9. Phenotypic observations, transcriptome analysis, and promoter-binding experiments revealed that GhHAM binds to the promoter of GoPGF, regulating pigment gland formation in cotton's multiple organs via the GoPGF-GhJUB1 module. The knockout of GhHAM significantly reduced gossypol production and increased cotton's susceptibility to pests in the field. Feeding assays demonstrated that more than 80% of the cotton bollworm larvae preferred ghham over the wild type. Furthermore, the ghham mutants displayed shorter cell length and decreased gibberellins (GA) production in the stem. Exogenous application of GA3 restored stem cell elongation but not gland formation, thereby indicating that GhHAM controls gland morphogenesis independently of GA. Our study sheds light on the functional differentiation of HAM proteins among plant species, highlights the significant role of pigment glands in influencing pest feeding preference, and provides a theoretical basis for breeding pest-resistant cotton varieties to address the challenges posed by frequent outbreaks of pests.

3.
Chem Biol Interact ; 398: 111090, 2024 Aug 01.
Artículo en Inglés | MEDLINE | ID: mdl-38825057

RESUMEN

Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play pivotal roles in the pathology of cerebral ischemia. In this study, we investigated whether phelligridimer A (PA), an active compound isolated from the medicinal and edible fungus Phellinus igniarius, ameliorates ischemic cerebral injury by restoring mitochondrial function and restricting ER stress. An in vitro cellular model of ischemic stroke-induced neuronal damage was established by exposing HT-22 neuronal cells to oxygen-glucose deprivation/reoxygenation (OGD/R). An in vivo animal model was established in rats subjected to middle cerebral artery occlusion/reperfusion (MCAO/R). The results showed that PA (1-10 µM) dose-dependently increased HT-22 cell viability, reduced OGD/R-induced lactate dehydrogenase release, and reversed OGD/R-induced apoptosis. PA reduced OGD/R-induced accumulation of reactive oxygen species, restored mitochondrial membrane potential, and increased ATP levels. Additionally, PA reduced the expression of the 78-kDa glucose-regulated protein (GRP78) and the phosphorylation of inositol-requiring enzyme-1α (p-IRE1α) and eukaryotic translation-initiation factor 2α (p-eIF2α). PA also inhibited the activation of the mitogen-activated protein kinase (MAPK) pathway in the OGD/R model. Moreover, treatment with PA restored the expression of mitofusin 2 (Mfn-2), a protein linking mitochondria and ER. The silencing of Mfn-2 abolished the protective effects of PA. The results from the animal study showed that PA (3-10 mg/kg) significantly reduced the volume of cerebral infarction and neurological deficits, which were accompanied by an increased level of Mfn-2, and decreased activation of the ER stress in the penumbra of the ipsilateral side after MCAO/R in rats. Taken together, these results indicate that PA counteracts cerebral ischemia-induced injury by restoring mitochondrial function and reducing ER stress. Therefore, PA might be a novel protective agent to prevent ischemia stroke-induced neuronal injury.


Asunto(s)
Isquemia Encefálica , Estrés del Retículo Endoplásmico , GTP Fosfohidrolasas , Ratas Sprague-Dawley , Especies Reactivas de Oxígeno , Daño por Reperfusión , Animales , Daño por Reperfusión/metabolismo , Daño por Reperfusión/prevención & control , Daño por Reperfusión/tratamiento farmacológico , GTP Fosfohidrolasas/metabolismo , Ratas , Masculino , Estrés del Retículo Endoplásmico/efectos de los fármacos , Ratones , Isquemia Encefálica/metabolismo , Isquemia Encefálica/tratamiento farmacológico , Especies Reactivas de Oxígeno/metabolismo , Chaperón BiP del Retículo Endoplásmico/metabolismo , Apoptosis/efectos de los fármacos , Línea Celular , Infarto de la Arteria Cerebral Media/metabolismo , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , Fármacos Neuroprotectores/farmacología , Proteínas Mitocondriales/metabolismo , Proteínas Mitocondriales/genética , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Glucosa/metabolismo , Supervivencia Celular/efectos de los fármacos , Proteínas Serina-Treonina Quinasas/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas de Choque Térmico/metabolismo , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Factor 2 Eucariótico de Iniciación/metabolismo
4.
Glia ; 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38785370

RESUMEN

We have previously shown that phosphodiesterase 4 (PDE4) inhibition protects against neuronal injury in rats following middle cerebral artery occlusion/reperfusion (MCAO/R). However, the effects of PDE4 on brain edema and astrocyte swelling are unknown. In this study, we showed that inhibition of PDE4 by Roflumilast (Roflu) reduced brain edema and brain water content in rats subjected to MCAO/R. Roflu decreased the expression of aquaporin 4 (AQP4), while the levels of phosphorylated protein kinase B (Akt) and forkhead box O3a (FoxO3a) were increased. In addition, Roflu reduced cell volume and the expression of AQP4 in primary astrocytes undergoing oxygen and glucose deprivation/reoxygenation (OGD/R). Consistently, PDE4B knockdown showed similar effects as PDE4 inhibition; and PDE4B overexpression rescued the inhibitory role of PDE4B knockdown on AQP4 expression. We then found that the effects of Roflu on the expression of AQP4 and cell volume were blocked by the Akt inhibitor MK2206. Since neuroinflammation and astrocyte activation are the common events that are observed in stroke, we treated primary astrocytes with interleukin-1ß (IL-1ß). Astrocytes treated with IL-1ß showed decreased AQP4 and phosphorylated Akt and FoxO3a. Roflu significantly reduced AQP4 expression, which was accompanied by increased phosphorylation of Akt and FoxO3a. Furthermore, overexpression of FoxO3a partly reversed the effect of Roflu on AQP4 expression. Our findings suggest that PDE4 inhibition limits ischemia-induced brain edema and astrocyte swelling via the Akt/FoxO3a/AQP4 pathway. PDE4 is a promising target for the intervention of brain edema after cerebral ischemia.

5.
Int J Gen Med ; 17: 2389-2405, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38808201

RESUMEN

Objective: Ubiquitination is an important post-translational modification. However, the significance of the TRIM family of E3 ubiquitin ligases in head and neck squamous cell carcinoma (HNSCC) has not been determined. In this study, the roles of TRIM E3 ubiquitin ligases in lymphovascular invasion in head and neck squamous cell carcinoma (HNSCC) were evaluated. Materials and Methods: TRIM expression and related parameters were obtained from UbiBrowser2.0, UALCAN, TIMER, TISIDB, LinkedOmics, STRING, and GeneMANIA databases. Immunohistochemistry was used to confirm their expression. Results: TRIM2, TRIM11, TRIM28, and TRIM56 were upregulated in HNSCC with lymphovascular invasion. TRIM expression was strongly associated with immune infiltration, including key treatment targets, like PD-1 and CTL4. Co-expressed genes and possible ubiquitination substrates included tumor-related factors. The TRIMs had predicted roles in ubiquitination-related pathways and vital signaling pathways, eg, MAPK, PI3K-Akt, and JAK-STAT signaling pathways. Conclusion: Ubiquitination mediated by four TRIMs might be involved in the regulation of tumor immunity, laying the foundation for future studies of the roles of the TRIM family on the prediction and personalized medicine in HNSCC. The four TRIMs might exert oncogenic effects by promoting lymphovascular invasion in HNSCC.

6.
Sheng Li Xue Bao ; 76(2): 289-300, 2024 Apr 25.
Artículo en Chino | MEDLINE | ID: mdl-38658377

RESUMEN

Sepsis-associated encephalopathy (SAE) refers to diffuse brain dysfunction caused by sepsis, which is characterized by decreased attention, directional impairment, being prone to irritation, and in severe cases the patient will experience drowsiness and coma. The pathogenesis of SAE mainly includes neuroinflammation, damage of blood-brain barrier, cerebral vascular dysfunction, and neurometabolic changes, among which neuroinflammation is the core pathological process. Microglia are considered to be important immune cells of the central nervous system and play an important role in neuroinflammation. This article systematically describes the role of microglia in the development of SAE, and discusses the phenotype and related signaling pathways of microglia, in order to clarify the role of microglia in SAE and provide a theoretical basis for clinical treatment of SAE.


Asunto(s)
Microglía , Encefalopatía Asociada a la Sepsis , Humanos , Encefalopatía Asociada a la Sepsis/fisiopatología , Encefalopatía Asociada a la Sepsis/metabolismo , Encefalopatía Asociada a la Sepsis/etiología , Microglía/metabolismo , Microglía/fisiología , Animales , Barrera Hematoencefálica/metabolismo , Transducción de Señal , Sepsis/complicaciones , Sepsis/fisiopatología , Enfermedades Neuroinflamatorias/etiología
7.
J Hazard Mater ; 471: 134316, 2024 Jun 05.
Artículo en Inglés | MEDLINE | ID: mdl-38669923

RESUMEN

OBJECTIVES: We examined the associations of self-reported exposures, and urinary metabolites related to household pesticide with cardiovascular disease (CVD) mortality in older adults based on the 2007 to 2014 waves of National Health and Nutrition Examination Survey (NHANES). METHODS: Information on application and urinary metabolites related to household pesticide exposure were collected. We estimated the risks of household pesticide exposure, urinary metabolites with subsequent incident CVD death using Cox proportional hazards regression models. The indirect effects of urinary metabolites and effect modifications were examined. RESULTS: The participants who reported exposure to household pesticide had a higher risk of incident CVD death (adjusted HR 1.40, 95% CI 1.08 to 1.81). Per 1-log10 increase in urinary N, N-diethyl-3-methylbenzamide (DEET) related to household insect repellents was associated with a higher risk of incident CVD death (adjusted HR 1.97, 95% CI 1.14 to 3.40). Urinary DEET explained 4.21% of the total association between household pesticide exposure and CVD death risk. The participants who persisted a low level of health diet exhibited pronounced CVD death risks with household pesticide exposures. CONCLUSIONS: Exposure to household pesticide, especially household insect repellents, was consistently associated with an elevated CVD death risk in older adults. A heatlhy diet could partly attenuate the associations.


Asunto(s)
Enfermedades Cardiovasculares , Exposición a Riesgos Ambientales , Plaguicidas , Humanos , Enfermedades Cardiovasculares/mortalidad , Enfermedades Cardiovasculares/orina , Masculino , Femenino , Anciano , Estudios Prospectivos , Exposición a Riesgos Ambientales/análisis , Exposición a Riesgos Ambientales/efectos adversos , Plaguicidas/orina , Plaguicidas/toxicidad , Persona de Mediana Edad , Encuestas Nutricionales , Repelentes de Insectos , DEET/orina , Anciano de 80 o más Años
8.
Sci Total Environ ; 926: 171717, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38490419

RESUMEN

Oxidation technologies based on peroxymonosulfate (PMS) have been effectively used for the remediation of soil organic pollutants due to their high efficiency. However, the effects of advanced PMS-based oxidation technologies on other soil pollutants, such as heavy metals, remain unknown. In this study, changes in the form of heavy metals in soil after using PMS and the risk of pollution to the ecological environment were investigated. Furthermore, two risk assessment methods, the mung bean germination toxicity test and groundwater leaching soil column test, were employed to evaluate the soil before and after PMS treatment. The results showed that PMS has a strong ability to degrade complex compounds, enabling the transformation of heavy metals, such as Cd, Pb, and Zn, from stable to active states in the soil. The risk assessments showed that PMS treatment activated heavy metals in the soil, which delayed the growth of plants, increased heavy metal content in plant tissues and the risk of groundwater pollution. These findings provide a new perspective for understanding the effects of PMS on soil, thus facilitating the sustained and reliable development of future research in the field of advanced oxidation applied to soil treatment.


Asunto(s)
Metales Pesados , Contaminantes del Suelo , Suelo , Metales Pesados/toxicidad , Metales Pesados/análisis , Peróxidos , Contaminantes del Suelo/toxicidad , Contaminantes del Suelo/análisis , Plantas , Medición de Riesgo , China , Monitoreo del Ambiente/métodos
9.
Vaccine ; 42(9): 2317-2325, 2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38433065

RESUMEN

BACKGROUND: Vaccination has been proven effective against infection with enterovirus A71 (EV-A71) in clinical trials, but vaccine effectiveness in real-world situations remains incompletely understood. Furthermore, it is not clear whether previous vaccination will result in symptom attenuation among post-vaccinated cases. METHODS: Based on long-term data extracted from the only designed referral hospital for infectious diseases, we used a test-negative case-control design and multivariate logistic regression models to analyze the effectiveness of EV-A71 vaccine against hand, foot and mouth disease (HFMD). And then, generalized linear regression models were used to evaluate the associations between prior vaccination and disease profiles. RESULTS: We selected 4883 inpatients for vaccine efficacy estimations and 2188 inpatients for disease profile comparisons. Vaccine effectiveness against EV-A71-induced HFMD for complete vaccination was 63.4 % and 51.7 % for partial vaccination. The vaccine effectiveness was higher among cases received the first dose within 12 months. No protection was observed against coxsackievirus (CV) A6-, CV-A10- or CV-A16-associated HFMD among children regardless of vaccination status. Completely vaccinated cases had shorter hospital stay and disease course compared to unvaccinated cases (P < 0.05). CONCLUSIONS: These findings reiterate the need to continue the development of a multivalent vaccine or combined vaccines, and have implications for introducing optimized vaccination strategies.


Asunto(s)
Enfermedades Transmisibles , Enterovirus Humano A , Infecciones por Enterovirus , Enterovirus , Enfermedad de Boca, Mano y Pie , Vacunas Virales , Niño , Humanos , Enfermedad de Boca, Mano y Pie/prevención & control , Infecciones por Enterovirus/prevención & control , Vacunación , Anticuerpos Antivirales , Antígenos Virales , Vacunas Combinadas , China
10.
Psychiatry Res ; 333: 115762, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38310687

RESUMEN

Traumatic events have significant negative impacts throughout one's life. We aimed to comprehensively examine the early associations between traumatic events and suicidality among adolescents. In a cross-sectional sample of 260,423 adolescents in Deyang, China in September 2021, we assessed individual traumatic events, cumulative types, and patterns, alongside suicide risk scores and ideation, attempts, or plans. Linear and Poisson regression models adjusted for demographic confounders evaluated the association. Robust associations existed between interpersonal violence-related traumatic events and higher suicidality, with physical abuse demonstrating the strongest correlation. Moreover, suicide risk scores displayed a clear trend, indicating a progressively stronger association with suicidality as cumulative traumatic event types increased. Four distinct traumatic patterns emerged, including low traumas, high physical abuse, high death/serious injuries of a loved one, and multiple traumas, with the latter showing the strongest association with suicidality. Notably, the stratified analysis showed these associations were more pronounced in females, urban residents, only children, left-behind children, and those aged 13-15, while weaker in participants from families with intact parental relationships and middle socioeconomic status. Understanding the role of demographic factors and traumatic patterns in identifying at-risk youth can enable early detection and targeted interventions for suicide-related concerns.


Asunto(s)
Suicidio , Femenino , Niño , Humanos , Adolescente , Estudios Transversales , Ideación Suicida , Violencia , Factores de Riesgo
11.
Clin Biochem ; 124: 110717, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38224931

RESUMEN

BACKGROUND: Recent studies have identified methylated SDC2 and NDRG4 in colorectal cancer (CRC), however, the diagnostic value of the combined two genes remains undefined. This study aims to investigate the methylation of SDC2 and NDRG4 in stool samples and their application in diagnosis of CRC. METHODS: Five groups were enrolled in our study which consisted of CRC (n = 138), advanced adenomas (n = 27), polyp (n = 35), intestinal disease control (n = 150), and healthy individuals (n = 28). Methylation status of SDC2 and NDRG4 in fecal samples were tested with appropriate commercial kits. Primary data were collected and statistical analyses were performed. RESULTS: The positive rates of both SDC2 and NDRG4 methylation in stool samples of CRC group were significantly higher (P < 0.001) than those of either group of advanced adenomas, or polyp, or intestinal disease or the healthy control. It was suggested that both methylated SDC2,NDRG4, SDC2/NDRG4 and age were independent risk factors for CRC. The sensitivity of SDC2 and NDRG4 for CRC diagnosis were 73.9 % and 63.0 %, respectively, while SDC2 combined with NDRG4 had a higher sensitivity of 85.5 %. The specificity of SDC2, NDRG4 and SDC2 combined with NDRG4 achieved 91.6 %, 88.3 % and 84.6 %, respectively. The AUC for methylated SDC2 and NDRG4 were 0.828 (95 % CI: 0.780-0.876) and 0.757 (95 % CI: 0.703-0.811), respectively. In contrast, SDC2 combined with NDRG4 improved the AUC to 0.850 (95 % CI: 0.807-0.893). CONCLUSIONS: This research confirmed the significance of detection of SDC2 and NDRG4 methylation by using noninvasive samples of stool. More importantly, attributing to their high level and frequency of methylation in stool, SDC2 and NDRG4 could be promising biomarkers for stool-based method for screening and early diagnosis of CRC, especially when combined.


Asunto(s)
Adenoma , Neoplasias Colorrectales , Humanos , Metilación de ADN , Sensibilidad y Especificidad , Neoplasias Colorrectales/diagnóstico , Neoplasias Colorrectales/genética , Biomarcadores de Tumor/genética , Biomarcadores de Tumor/análisis , Heces/química , Detección Precoz del Cáncer/métodos , Adenoma/diagnóstico , Adenoma/genética , Proteínas Musculares/genética , Proteínas del Tejido Nervioso , Sindecano-2/genética
12.
J Clin Endocrinol Metab ; 109(2): e531-e542, 2024 Jan 18.
Artículo en Inglés | MEDLINE | ID: mdl-37793167

RESUMEN

CONTEXT: Volatile organic compounds (VOCs) are pervasive environmental pollutants that have been linked to various adverse health effects. However, the effect of ambient VOCs, whether individually or in mixtures, on diabetes remains uncertain and requires further investigation. OBJECTIVE: This study investigates the effects of ambient VOCs exposure, whether single or mixed, on diabetes mellitus and glucose homeostasis in the general population. METHODS: Urinary concentrations of VOC metabolites were obtained from the National Health and Nutrition Examination Survey. Survey-weighted logistic regression and generalized linear regression were used to explore the associations between individual VOC exposure and diabetes risk and glucose homeostasis indicators, respectively. Weighted quantile sum (WQS) regression models were applied to assess the combined effects of VOC mixtures. RESULTS: Out of 8468 participants, 1504 had diabetes mellitus. Eight VOC metabolites showed positive associations with diabetes mellitus (OR, 1.15-1.43; all P < .05), insulin resistance (IR) (OR, 1.02-1.06; P < .05), and other glucose homeostasis indicators (ß, 0.04-2.32; all P < .05). Mixed VOC models revealed positive correlations between the WQS indices and diabetes risk (OR = 1.52; 95% CI, 1.29-1.81), IR (OR = 1.36; 95% CI, 1.14-1.62), and other glucose homeostasis indicators (ß, 0.17-2.22; all P < .05). CONCLUSION: Urinary metabolites of ambient VOCs are significantly associated with an increased diabetes risk and impaired glucose homeostasis. Thus, primary prevention policies aimed at reducing ambient VOCs could attenuate diabetes burden.


Asunto(s)
Diabetes Mellitus , Resistencia a la Insulina , Compuestos Orgánicos Volátiles , Humanos , Monitoreo del Ambiente , Encuestas Nutricionales , Diabetes Mellitus/epidemiología , Glucosa
14.
New Phytol ; 241(1): 314-328, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37865884

RESUMEN

Gossypol and the related terpenoids are stored in the pigment gland to protect cotton plants from biotic stresses, but little is known about the synthetic sites of these metabolites. Here, we showed that GoPGF, a key gene regulating gland formation, was expressed in gland cells and roots. The chromatin immunoprecipitation sequencing (ChIP-seq) analysis demonstrated that GoPGF targets GhJUB1 to regulate gland morphogenesis. RNA-sequencing (RNA-seq) showed high accumulation of gossypol biosynthetic genes in gland cells. Moreover, integrated analysis of the ChIP-seq and RNA-seq data revealed that GoPGF binds to the promoter of several gossypol biosynthetic genes. The cotton callus overexpressing GoPGF had dramatically increased the gossypol levels, indicating that GoPGF can directly activate the biosynthesis of gossypol. In addition, the gopgf mutant analysis revealed the existence of both GoPGF-dependent and -independent regulation of gossypol production in cotton roots. Our study revealed that the pigment glands are synthetic sites of gossypol in aerial parts of cotton and that GoPGF plays a dual role in regulating gland morphogenesis and gossypol biosynthesis. The study provides new insights for exploring the complex relationship between glands and the metabolites they store in cotton and other plant species.


Asunto(s)
Gosipol , Gosipol/metabolismo , Gossypium/genética , Gossypium/metabolismo , Terpenos , Componentes Aéreos de las Plantas
15.
J Med Chem ; 67(1): 728-753, 2024 01 11.
Artículo en Inglés | MEDLINE | ID: mdl-38156615

RESUMEN

Alcohol use disorder (AUD) results in numerous disabilities and approximately 3 million deaths annually, caused mainly by alcoholic liver disease (ALD). Phosphodiesterase IV (PDE4) has emerged as an attractive molecular target for a new treatment for AUD and ALD. In this study, we describe the identification of 5-azaindazole analogues as PDE4 inhibitors against AUD and ALD. System optimization studies led to the discovery of ZL40 (IC50 = 37.4 nM) with a remarkable oral bioavailability (F = 94%), satisfactory safety, and a lower emetogenic potency than the approved PDE4 inhibitors roflumilast and apremilast. Encouragingly, ZL40 exhibited AUD therapeutic effects by decreasing alcohol intake and improving acute alcohol-induced sedation and motor impairment. Meanwhile, ZL40 displayed the potential to alleviate alcoholic liver injury and attenuate inflammation in the NIAAA mice model. These results showed that ZL40 is a promising compound for future drug development to treat alcohol-related diseases.


Asunto(s)
Alcoholismo , Hepatopatías Alcohólicas , Inhibidores de Fosfodiesterasa 4 , Ratones , Animales , Inhibidores de Fosfodiesterasa 4/farmacología , Inhibidores de Fosfodiesterasa 4/uso terapéutico , Alcoholismo/tratamiento farmacológico , Hepatopatías Alcohólicas/tratamiento farmacológico , Etanol/uso terapéutico , Consumo de Bebidas Alcohólicas
16.
Exp Neurol ; 373: 114654, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38104887

RESUMEN

We have previously demonstrated that treatment with cannabidiol (CBD) ameliorates mitochondrial dysfunction and attenuates neuronal injury in rats following cerebral ischemia. However, the role of CBD in the progression of ischemic stroke-induced inflammation and the molecules involved remain unclear. Here, we found that CBD suppressed the production of interleukin-1ß (IL-1ß) and tumor necrosis factor-α (TNF-α), reduced the activation of microglia, ameliorated mitochondrial deficits, and decreased the phosphorylation of nuclear factor κ-B (NF-κB) in BV-2 cells subjected to oxygen-glucose deprivation/reoxygenation (OGD/R). Cyclin-dependent kinase regulatory subunit 1B (CKS1B) expression was decreased in BV-2 cells following OGD/R and this reduction was blocked by treatment with CBD. Knockdown of CKS1B increased the activation of microglia and enhanced the production of IL-1ß and TNF-α in BV-2 cells treated with CBD. Moreover, CKS1B knockdown exacerbated mitochondrial deficits and increased NF-κB phosphorylation. CBD treatment also ameliorated brain injury, reduced neuroinflammation, and enhanced the protein levels of mitochondrial transcription factor A and CKS1B in rats following middle cerebral artery occlusion/reperfusion. These data identify CKS1B as a novel regulator of neuroinflammation; and reveals its involvement in the anti-inflammatory effects of CBD. Interventions targeting CKS1B expression are potentially promising for treating in ischemic stroke.


Asunto(s)
Isquemia Encefálica , Cannabidiol , Accidente Cerebrovascular Isquémico , Daño por Reperfusión , Accidente Cerebrovascular , Animales , Ratas , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Isquemia Encefálica/metabolismo , Cannabidiol/farmacología , Cannabidiol/uso terapéutico , Infarto de la Arteria Cerebral Media/complicaciones , Infarto de la Arteria Cerebral Media/tratamiento farmacológico , Microglía/metabolismo , Enfermedades Neuroinflamatorias , FN-kappa B/metabolismo , Oxígeno/farmacología , Daño por Reperfusión/metabolismo , Transducción de Señal , Accidente Cerebrovascular/tratamiento farmacológico , Accidente Cerebrovascular/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo
17.
Front Endocrinol (Lausanne) ; 14: 1259475, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37929032

RESUMEN

Objective: To investigate whether prior cholecystectomy is associated with incident osteoporosis. Background: Cholecystectomy may have consequences involving abnormal metabolism. Studies investigating the association between prior cholecystectomy and osteoporosis have yielded inconsistent results. Methods: In total, 17,603 UK Biobank participants underwent cholecystectomy, and 35,206 matched controls were included in this study. They were followed up for incident osteoporosis, which was determined using ICD-10 codes (M80-82). The association between cholecystectomy and osteoporosis was assessed using Cox proportional regression modeling. The association between osteoporosis risk and cholecystectomy was further analyzed across age, sex, serum vitamin D level, and body mass index (BMI) categories. Results: Within a median follow-up period of 13.56 years, 3,217 participants were diagnosed with osteoporosis. After adjustment for relevant confounders, prior cholecystectomy was associated with a 1.21 times higher risk of osteoporosis in women (hazard ratio (HR): 1.21 [95% CI, 1.12-1.31], p < 0.001) and a 1.45 times higher risk in men (HR: 1.45 [95% CI, 1.10-1.90], p = 0.007). In women, the association was stronger for patients who were aged 40-55 years, with BMI < 18.5 kg/m2, and vitamin D between 30 and 50 nmol/ml. No significant interactions between cholecystectomy and income level, education level, presence of hypertension, or diabetes were identified in either sex. Conclusions: Our findings indicated that people who underwent cholecystectomy had a higher risk of developing osteoporosis after adjustment for potential confounders. Our findings suggest that awareness of the risk of osteoporosis in patients with a history of cholecystectomy is merited.


Asunto(s)
Bancos de Muestras Biológicas , Osteoporosis , Masculino , Humanos , Femenino , Estudios Prospectivos , Osteoporosis/epidemiología , Osteoporosis/etiología , Vitamina D , Colecistectomía/efectos adversos , Reino Unido/epidemiología
18.
Nat Commun ; 14(1): 7392, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37968319

RESUMEN

Verticillium dahliae is a soil-borne hemibiotrophic fungal pathogen that threatens cotton production worldwide. In this study, we assemble the genomes of two V. dahliae isolates: the more virulence and defoliating isolate V991 and nondefoliating isolate 1cd3-2. Transcriptome and comparative genomics analyses show that genes associated with pathogen virulence are mostly induced at the late stage of infection (Stage II), accompanied by a burst of reactive oxygen species (ROS), with upregulation of more genes involved in defense response in cotton. We identify the V991-specific virulence gene SP3 that is highly expressed during the infection Stage II. V. dahliae SP3 knock-out strain shows attenuated virulence and triggers less ROS production in cotton plants. To control the disease, we employ polyethyleneimine-coated MXene quantum dots (PEI-MQDs) that possess the ability to remove ROS. Cotton seedlings treated with PEI-MQDs are capable of maintaining ROS homeostasis with enhanced peroxidase, catalase, and glutathione peroxidase activities and exhibit improved tolerance to V. dahliae. These results suggest that V. dahliae trigger ROS production to promote infection and scavenging ROS is an effective way to manage this disease. This study reveals a virulence mechanism of V. dahliae and provides a means for V. dahliae resistance that benefits cotton production.


Asunto(s)
Ascomicetos , Puntos Cuánticos , Verticillium , Resistencia a la Enfermedad/genética , Especies Reactivas de Oxígeno/metabolismo , Polietileneimina , Gossypium/genética , Ascomicetos/metabolismo , Enfermedades de las Plantas/microbiología , Regulación de la Expresión Génica de las Plantas
19.
Nutrition ; 116: 112189, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37689015

RESUMEN

OBJECTIVES: Future primary prevention strategies may benefit from understanding the connection between mortality in individuals with central obesity and modifiable lifestyle factors like dietary intake. This study sought to determine whether there was a separate relationship between folate, vitamin B6, and vitamin B12 intake and all-cause and cause-specific mortality in the US population with central obesity. METHODS: The study analyzed data from the National Health and Nutrition Examination Survey between 1999 and 2016. Using the Cox proportional hazards model, the association between dietary intake of B vitamins and all-cause and cause-specific mortality was examined. A total of 7718 adults with central obesity were enrolled, with a mean age of 49.87 (SD = 0.25) y at baseline. RESULTS: Folate intake was independently associated with a decreased incidence of all-cause mortality (adjusted hazard ratio = 0.71; 95% CI, 0.58-0.87). Furthermore, higher intake of vitamin B6 and vitamin B12 was inversely correlated with cardiovascular disease mortality (adjusted hazard ratio = 0.63; 95% CI, 0.40-0.98; and adjusted hazard ratio = 0.44; 95% CI, 0.29-0.65, respectively) and the finding reveal an interaction between homocysteine and vitamin B12 and folate on All-cause mortality CONCLUSIONS: The findings of this study suggest that vitamin B12 and folate intake may be protective factors in individuals with central obesity. It is important to consider both their total homocysteine level and body mass index in conjunction with these nutrients. Further research is needed to validate these findings.


Asunto(s)
Complejo Vitamínico B , Adulto , Humanos , Persona de Mediana Edad , Encuestas Nutricionales , Obesidad Abdominal , Causas de Muerte , Ácido Fólico , Vitamina B 12 , Vitamina B 6 , Piridoxina , Homocisteína
20.
JHEP Rep ; 5(10): 100819, 2023 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-37691690

RESUMEN

Background & Aims: Sleep duration has been linked to metabolic dysfunction and chronic inflammation, which may contribute to the development of liver cancer and chronic liver disease (CLD). However, little is known about the relationship between sleep or napping duration and hepatocellular carcinoma (HCC) risk and CLD mortality. Methods: We followed 295,837 individuals in the National Institutes of Health-American Association of Retired Persons (NIH-AARP) Diet and Health Study. We examined the associations of nighttime sleep duration and daytime napping duration with risk of HCC incidence and CLD mortality. Cox proportional hazards regression was used to calculate multivariable hazard ratios (HRs) and 95% confidence intervals (95% CIs). Results: A total of 357 incident HCC cases and 578 CLD deaths were identified after a median follow-up time of 15.5 years. After adjusting for confounder factors, we found U-shaped associations of nighttime sleep duration with the incidence of HCC (HR<5 vs. 7-8 h = 2.00, 95% CI: 1.22-3.26 and HR≥9 vs. 7-8 h = 1.63, 95% CI: 1.04-2.65) and CLD mortality (HR<5 vs. 7-8 h = 1.78, 95% CI: 1.18-2.69 and HR≥9 vs. 7-8 h = 1.91, 95% CI: 1.35-2.70). Daytime napping was associated with higher risk of HCC (HR≥1 vs. non-nappers = 1.46, 95% CI: 1.04-2.06) and higher CLD mortality (HR≥1 h vs. non-nappers = 1.54, 95% CI: 1.18-2.01) compared with no napping. Conclusions: We observed U-shaped associations for nighttime sleeping and risk of HCC and CLD mortality. Additionally, longer daytime napping duration was associated with higher risk of HCC and CLD death. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep. Impact and implications: Sleep or napping duration may play a role in the development of liver cancer and chronic liver disease, but little is known about the relationship between them. In addition, abnormal sleep patterns in patients with chronic liver disease may further promote the development of liver disease, creating a vicious cycle. Our study suggests that clinical follow up of individuals at risk for liver cancer or living with a liver disease should include information on nighttime and daytime sleep, as they can be potentially important factors in the development and progression of liver disease.

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