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1.
Sci Bull (Beijing) ; 2024 Sep 24.
Artículo en Inglés | MEDLINE | ID: mdl-39366826

RESUMEN

Biliary tract carcinoma (BTC) is a group of malignant tumors that originate in the digestive system and occurs with a high incidence in China. Few consistent and comparable assessments of BTC disease burden have been conducted at national or subnational levels, and little is known about the demographic, temporal, and geographic patterns of epidemiological characteristics and disease burden of BTC in China. The incidence, mortality, disability-adjusted life-years (DALYs), years of life lost (YLLs) due to premature death and years lived with disability (YLDs) of BTC were comprehensively examined by age, sex, and calendar year in the Chinese population, using the methodological framework and analytical strategies used for the 2021 Global Burden of Disease study. All-age incidence increased from 17,077 to 51,720 between 1990 and 2021, and the age-standardized incidence rate rose by 13.62%; all-age deaths increased from 17,251 to 37,833, but the age-standardized mortality rate fell by nearly one-fifth. The DALYs rose by 89.57% while the age-standardized DALY rate fell by 23.24%. Variations of the tendencies in BTC burden were found between sexes and age groups. Data for each provincial region indicate that coastal eastern provincial regions have higher incidence and YLD levels, whereas northern provincial regions have higher mortality, DALY, and YLL levels. The proportions of DALYs attributable to high body mass index (BMI) illustrate the growing attribution obesity has made, and high BMI usually puts more burden on northern provincial regions. These results provide evidence to support precise, targeted, and customed public health strategies aimed at enhancing biliary tract health among the Chinese population.

2.
Am J Gastroenterol ; 2024 Oct 09.
Artículo en Inglés | MEDLINE | ID: mdl-39382852

RESUMEN

INTRODUCTION: The course of maternal antiviral prophylaxis to prevent mother-to-child transmission of hepatitis B virus (HBV-MTCT) varies greatly, and it has not been demonstrated in a randomized controlled study. METHODS: In this multicenter, open-label, randomized controlled trial, eligible pregnant women with HBV DNA of 5.3-9.0 log10 IU/mL who received tenofovir alafenamide fumarate (TAF) from the first day of 33 gestational weeks to delivery (expected eight-week) or to four-week postpartum (expected twelve-week) were randomly enrolled at a 1:1 ratio and followed until six-month postpartum. All infants received standard immunoprophylaxis (hepatitis B immunoglobulin and vaccine). The primary endpoint was the safety of mothers and infants. The secondary endpoint was infants' HBV-MTCT rate at seven months of age. RESULTS: Among 119 and 120 intention-to-treat pregnant women, 115 and 116 women were followed until delivery, and 110 and 112 per-protocol mother-infant dyads in two groups completed the study. Overall, TAF was well tolerated, no one discontinued therapy due to adverse events (0/239, 0%, 95% confidence interval [CI] 0%-1.6%), and no infant had congenital defects or malformations at delivery (0/231, 0%, 95% CI 0%-1.6%). The infants' physical development at birth (n=231) and at seven months (n=222) were normal. Furthermore, 97.0% (224/231, 95% CI 93.9%-98.5%) of women achieved HBV DNA <5.3 log10 IU/mL at delivery. The intention-to-treat and per-protocol infants' HBV-MTCT rates were 7.1% (17/239, 95% CI 4.5%-11.1%) and 0% (0/222, 95% CI 0%-1.7%) at seven months of age. Comparatively, 15.1% (18/119, 95% CI 9.8%-22.7%) versus 18.3% (22/120, 95% CI 12.4%-26.2%) of women in the two groups had mildly elevated alanine aminotransferase levels at three-month and six-month postpartum, respectively (P=0.507); notably, no one experienced alanine aminotransferase flare (0% [0/119, 95% CI 0%-3.1%] versus 0% [0/120, 0%-3.1%]). DISCUSSION: Maternal TAF prophylaxis to prevent HBV-MTCT is generally safe and effective, and expected eight-week prenatal duration is feasible. ClinicalTrials.gov, NCT04850950.

3.
Bioinformatics ; 2024 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-39392404

RESUMEN

MOTIVATION: Target discovery is a crucial step in drug development, as it directly affects the success rate of clinical trials. Knowledge graphs (KGs) offer unique advantages in processing complex biological data and inferring new relationships. Existing biomedical KGs primarily focus on tasks such as drug repositioning and drug-target interactions, leaving a gap in the construction of KGs tailored for target discovery. RESULTS: We established a comprehensive biomedical KG focusing on target discovery, termed TarKG, by integrating seven existing biomedical KGs, nine public databases, and traditional Chinese medicine knowledge databases. TarKG consists of 1,143,313 entities and 32,806,467 relations across 15 entity categories and 171 relation types, all centered around three core entity types: Disease, Gene, Compound. TarKG provides specialized knowledges for the core entities including chemical structures, protein sequences or text descriptions. By using different KG embedding algorithms, we assessed the knowledge completion capabilities of TarKG, particularly for disease-target link prediction. In case studies, we further examined TarKG's ability to predict potential protein targets for Alzheimer's disease (AD) and to identify diseases potentially associated with the metallo-deubiquitinase CSN5, using literature analysis for validation. Furthermore, we provided a user-friendly web server (https://tarkg.ddtmlab.org) that enables users to perform knowledge retrieval and relation inference using TarKG. AVAILABILITY: TarKG is accessible at https://tarkg.ddtmlab.org. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

4.
Int Immunopharmacol ; 143(Pt 1): 113284, 2024 Oct 07.
Artículo en Inglés | MEDLINE | ID: mdl-39378657

RESUMEN

Calcium oxalate (CaOx) crystals are the main constituents of renal crystals in humans and induce tubular lumen damage in renal tubules, leading to renal calcium deposition and kidney stone formation. Oxidative stress and inflammation play important roles in regulating calcium oxalate-induced injury. Here, we evaluated the efficacy in inhibiting oxidation and inflammation of pectinolinarigenin, a biologically active natural metabolite, in CaOx nephrocalcinosis and further explored its targets of action. First, we developed cellular and mouse models of calcium oxalate renal nephrocalcinosis and identified the onset of oxidative stress and inflammation according to experimental data. We found that pectolinarigenin inhibited this onset while reducing renal crystal deposition. Network pharmacology was subsequently utilized to screen for hypoxia-inducible factor-1α (HIF-1α), a regulator involved in the body's release and over-oxidation of inflammatory factors. Finally, molecular docking, cellular thermal shift assay, and other experiments to detect HIF-1α expression showed that pectolinarigenin directly combined with HIF-1α and prevented downstream reactive oxygen species activation and release. Our results indicate that pectolinarigenin can target and inhibit HIF-1α-mediated inflammatory responses and oxidative stress damage and be a novel drug for CaOx nephrocalcinosis treatment.

5.
BMJ Open ; 14(10): e086050, 2024 Oct 08.
Artículo en Inglés | MEDLINE | ID: mdl-39384240

RESUMEN

OBJECTIVES: This study aimed to investigate the prevalence of diabetes using structural equation modelling (SEM) to examine the pathways and associations of socioeconomic and lifestyle factors on diabetes in rural southwest China. DESIGN: Data were collected from a cross-sectional health interview and examination survey among individuals aged ≥35 years in rural southwest China. Fasting blood glucose, blood pressure, height, weight and waist circumference (WC) were measured for each participant. SEM was employed to assess the relationships between demographic characteristics (sex, age and ethnicity), socioeconomic position (SEP; annual household income, education level and access to medical services), lifestyle factors (obesity status (body mass index and WC) and physical inactivity), hypertension, hyperlipidaemia and family history of diabetes. SETTING: This study was conducted in rural Yunnan Province of China. PARTICIPANTS: 7536 individuals aged ≥35 years consented to participate in the study. RESULTS: The overall prevalence of diabetes in the present study was 8.3%. Prevalence did not differ by gender (prevalence for both men and women was 8.3% (p>0.05)). The results of SEM indicated that SEP, age, ethnicity, obesity status and physical inactivity had both significant direct and indirect effects on diabetes, with total effect size of 0.091, 0.149, -0.094, 0.212 and 0.089, respectively (p<0.01). Family history of diabetes (0.128, p<0.01), hypertension (0.135, p<0.01) and hyperlipidaemia (0.137, p<0.01) were directly associated with diabetes. CONCLUSIONS: Socioeconomic and lifestyle factors have both direct and indirect effects on prevalence of diabetes in rural southwest China. Future efforts to implement comprehensive interventions to promote the prevention and control of diabetes should in particular focus on obese individuals.


Asunto(s)
Diabetes Mellitus , Estilo de Vida , Población Rural , Factores Socioeconómicos , Humanos , Masculino , China/epidemiología , Femenino , Persona de Mediana Edad , Estudios Transversales , Prevalencia , Población Rural/estadística & datos numéricos , Diabetes Mellitus/epidemiología , Adulto , Anciano , Obesidad/epidemiología , Factores de Riesgo , Hipertensión/epidemiología , Análisis de Clases Latentes , Índice de Masa Corporal
7.
Int J Mol Med ; 54(6)2024 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-39370812

RESUMEN

Following the publication of this paper, it was drawn to the Editor's attention by a concerned reader that certain of the immunohistochemical images shown in Fig. 2B and C on p. 896 were strikingly similar to data appearing in different form in other articles written by different authors at different research institutes that had already been published before this paper was received at International Journal of Molecular Medicine (several of which have been retracted). Moreover, the flow-cytometric data shown in Fig. 2A appeared to be potentially anomalous. In view of the fact that the abovementioned data had already apparently been published prior to the submission of this paper to International Journal of Molecular Medicine, the Editor has decided that the article should be retracted from the Journal. The authors were asked for an explanation to account for these concerns, but the Editorial Office did not receive a reply. The Editor apologizes to the readership for any inconvenience caused. [International Journal of Molecular Medicine 43: 890-900, 2019; DOI: 10.3892/ijmm.2018.4006].

9.
Heliyon ; 10(19): e38091, 2024 Oct 15.
Artículo en Inglés | MEDLINE | ID: mdl-39391485

RESUMEN

Aims: We sought to reveal the landscape of epithelial cell subpopulations in the human esophageal squamous cell carcinoma microenvironment and investigate their parts on esophageal squamous carcinoma (ESCC) development. Background: Epithelial cells play an important role in the occurrence and development of ESCC through multiple mechanisms. While the landscape of epithelial cell subpopulations in ESCC, remains unclear. Objective: Exploring the role of epithelial cell subpopulations in ESCC progression. Methods: Seurat R package was used for single-cell RNA sequencing (scRNA-seq) data filtering, dimensionality reduction, clustering and differentially expressed genes analysis. Cellmarker database was adopted for cell cluster annotation. Functional enrichment analysis was carried out by Gene Ontology (GO) analysis. InferCNV package was conducted for copy number variation (CNV) of epithelial cell subpopulations in all chromosomal regions. Pseudotime trajectory analysis was implemented for exploring differentiation trajectory of epithelial cells subgroups during the cancer progression. CellChat analysis was used for probing the interactions between epithelial cells and NK/T cells. cellular experiments were performed using Quantitative Real-Time Polymerase Chain Reaction (RT-qPCR), Wound-Healing Assay and transwell. Results: 11 major cell subpopulations were identified in ESCC and adjunct tissues. Further reclassification of epithelial cells uncovered 4 subpopulations. Enrichment analysis revealed that highly expressed genes in 4 epithelial cell subpopulations were related to cell proliferation, immune response and angiogenesis. CNV analysis found that UBD + epithelial cells and GAS2L3+ epithelial cells had a higher proportion of CNV. Cell differentiation trajectories disclosed that KRT6C+ and GSTA1+ epithelial cells were in an intermediate state of differentiation, while UBD+ and GAS2L3+ epithelial cells are in an end state of differentiation during ESCC progression. Finally, we found that four epithelial cell subpopulations all inhibited NK/T cells through NECTIN2-TIGIT and CLEC2B-KLRB1. Low ATF3 and DDIT3 mRNA expression inhibited ESCC cell migration and invasion. Conclusion: Here, we obtained a through epithelial cell atlas of ESCC at single-cell resolution, explored the role of epithelial cell in ESCC progression, and unveiled immunosuppressive signals to NK/T cells in promoting ESCC. Our findings expand the comprehension of epithelial cells and offer a theoretical guidance for future anti-epithelial cell treatment of ESCC.

10.
J Diabetes Investig ; 2024 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-39387466

RESUMEN

AIMS/INTRODUCTION: This study aimed to identify low- and high-risk diabetes groups within prediabetes populations using data from the Taiwan Biobank (TWB) and UK Biobank (UKB) through a clustering-based Unsupervised Learning (UL) approach, to inform targeted type 2 diabetes (T2D) interventions. MATERIALS AND METHODS: Data from TWB and UKB, comprising clinical and genetic information, were analyzed. Prediabetes was defined by glucose thresholds, and incident T2D was identified through follow-up data. K-means clustering was performed on prediabetes participants using significant features determined through logistic regression and LASSO. Cluster stability was assessed using mean Jaccard similarity, silhouette score, and the elbow method. RESULTS: We identified two stable clusters representing high- and low-risk diabetes groups in both biobanks. The high-risk clusters showed higher diabetes incidence, with 15.7% in TWB and 13.0% in UKB, compared to 7.3% and 9.1% in the low-risk clusters, respectively. Notably, males were predominant in the high-risk groups, constituting 76.6% in TWB and 52.7% in UKB. In TWB, the high-risk group also exhibited significantly higher BMI, fasting glucose, and triglycerides, while UKB showed marginal significance in BMI and other metabolic indicators. Current smoking was significantly associated with increased diabetes risk in the TWB high-risk group (P < 0.001). Kaplan-Meier curves indicated significant differences in diabetes complication incidences between clusters. CONCLUSIONS: UL effectively identified risk-specific groups within prediabetes populations, with high-risk groups strongly associated male gender, higher BMI, smoking, and metabolic markers. Tailored preventive strategies, particularly for young males in Taiwan, are crucial to reducing T2D risk.

11.
Eur J Neurosci ; 2024 Oct 02.
Artículo en Inglés | MEDLINE | ID: mdl-39358869

RESUMEN

Freezing of gait (FOG) is a disabling motor symptom prevalent in patients with Parkinson's disease (PD); however, its pathophysiological mechanisms are poorly understood. This study aimed to investigate whole-brain functional connectivity (FC) pattern alterations in PD patients with FOG. A total of 18 PD patients, 10 with FOG (PD-FOG) and 8 without FOG (PD-nFOG), and 10 healthy controls were enrolled. High-resolution 3D T1-weighted and resting-state functional MRI (rs-fMRI) data were obtained from all participants. The groups' internetwork connectivity differences were explored with rs-fMRI FC using seed-based analysis and graph theory. Multiple linear regression analysis estimated the relationship between FC changes and clinical measurements. Rs-fMRI analysis demonstrated alterations in FC in various brain regions between the three groups. Freezing of Gait Questionnaire severity was correlated with decreased brain functional connection between Vermis12 and the left temporal occipital fusiform cortex (r = -0.82, P < .001). Graph theory topological metrics indicated a decreased clustering coefficient in the right superior temporal gyrus in the PD-nFOG group. PD-FOG patients exhibited a compensatory increase in connectivity between the left inferior frontal gyrus language network and the postcentral gyrus compared to PD-nFOG patients. Further, the decreased connection between Vermis 12 and the left temporal occipital fusiform cortex may serve as a potential neuroimaging biomarker for tracking PD-FOG and distinguishing between PD subtypes.

12.
Heliyon ; 10(16): e36039, 2024 Aug 30.
Artículo en Inglés | MEDLINE | ID: mdl-39247298

RESUMEN

In order to adjust and detect micro-nano periodic structure optical surface accurately and efficiently, the problem of composite scattering between micro-ellipsoidal periodic structure optical surface and pore defects is studied use the multi-resolution time domain (MRTD) approach. A calculation model is established for the intensity distribution of composite scattering, which is modulated by the micro-ellipsoidal periodic structure optical surface and microdefects. Results are in good agreement with those obtained using CST Microwave Studio software and the finite-different time-domain (FDTD) approach, which demonstrates the effectiveness of the calculation model and method. By combining the field distribution of the micro-ellipsoidal periodic structure optical surface containing microdefects with the optical response at different wavelengths, it is necessary to study the influence of various parameters of the micro-ellipsoidal structure and microdefects on the optical system of metamaterials. The effects of the parameters such as roughness, structure of micro-ellipsoidal unit, defect sizes and buried depths on the composite scattering characteristics are analyzed numerically. The results provide technical support for the fields of functional surface design, ultrasensitive detection, scattering peak orientation and frequency selection.

13.
Clin Lab ; 70(9)2024 Sep 01.
Artículo en Inglés | MEDLINE | ID: mdl-39257134

RESUMEN

BACKGROUND: Sarcopenia is a complication that occurs after liver transplantation (LT), and it is a poor prognostic factor. METHODS: A total of 23 healthy controls and 131 LT patients (18 - 76 weeks of age) were enrolled in the study. Pa-tients were grouped according to the North American Working Group on Sarcopenia in Liver Transplantation by performing pre- and post-transplant CT scans of the third lumbar (L3). The serum C-reactive protein (CRP) was analyzed and the liver frailty index (LFI) was assessed. Their associations with postoperative sarcopenia, skeletal muscle index (SMI), and poor outcomes were examined. RESULTS: Before LT, the serum CRP was increased in patients with LT, compared with the healthy subjects, and had the highest levels in patients with sarcopenia. There were seventy-nine patients with sarcopenia after LT, including 48 who had been diagnosed with sarcopenia preoperatively and 31 who had a new onset of sarcopenia after LT. There was a moderate-strength negative correlation between the preoperative and postoperative rates of change in CRP and L3 SMI. Patients assessed as frail preoperatively (LFI ≥ 4.5) were associated with postoperative sarcopenia, and 19 of the new postoperative sarcopenia cases occurred in patients assessed as frail preoperatively. The serum CRP levels and LFI were significantly higher in patients who experienced a prolonged hospitalization and early infections postoperatively than in patients without significant adverse events. CRP (post-LT) > 2.575 pg/mL (OR = 1.16, 95% CI: 1.06 - 2.39, p = 0.026) as well as frailty (OR = 1.36, 95% CI: 1.20 - 2.60, p = 0.001) were independent predictors of sarcopenia after LT in patients. CONCLUSIONS: Serum CRP levels and LFI may be effective for an early detection of sarcopenia in patients with LT.


Asunto(s)
Proteína C-Reactiva , Fragilidad , Trasplante de Hígado , Sarcopenia , Humanos , Sarcopenia/sangre , Sarcopenia/diagnóstico , Sarcopenia/etiología , Proteína C-Reactiva/análisis , Proteína C-Reactiva/metabolismo , Trasplante de Hígado/efectos adversos , Masculino , Femenino , Fragilidad/sangre , Fragilidad/diagnóstico , Fragilidad/complicaciones , Persona de Mediana Edad , Adulto , Hígado/diagnóstico por imagen , Complicaciones Posoperatorias/sangre , Complicaciones Posoperatorias/diagnóstico , Complicaciones Posoperatorias/etiología , Complicaciones Posoperatorias/epidemiología , Resultado del Tratamiento , Biomarcadores/sangre , Pronóstico , Anciano , Estudios de Casos y Controles , Factores de Riesgo
14.
HERD ; : 19375867241276299, 2024 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-39263722

RESUMEN

Objectives: Chinese classical gardens, designated as a vital world cultural heritage, embody a lasting legacy transcending generation. Despite the cultural importance of these gardens, a notable research gap exists in deciphering the nuanced emotional and physiological responses triggered by individual elements within classical garden landscapes. Our research question aims to uncover the specific emotional and physiological impacts of key garden elements-plants, architecture, waterscape, and rockery-on visitors, with a particular focus on the Humble Administrator's Garden. These elements serve as the primary subjects for video capture at four sites. Study Design: A within-subject design experiment was used. Methods: Videos were recorded at these sites, encompassing visual, auditory, and tactile elements. Ninety-five participants watched these videos in an indoor setting. While viewing, we measured participants' physiological responses, including heart rate variability, skin conductance, and skin temperature, will be monitored alongside subjective assessments obtained through self-reported questionnaires such as the Emotional Perception Scale and State-Trait Anxiety Scale. Results: Findings suggest that while all landscape types evoke positive emotions, natural elements exert a more profound influence. Additionally, the Large Rockery emerges as a focal point, indicating enhanced emotional relaxation through auditory and tactile stimuli, particularly among younger individuals. Conclusions: This research contributes to the broader understanding of how classical gardens impact human emotions and well-being, offering insights that can inform future landscape design and promote mental health in diverse cultural contexts.

15.
Carbohydr Polym ; 346: 122632, 2024 Dec 15.
Artículo en Inglés | MEDLINE | ID: mdl-39245500

RESUMEN

The fabrication of multi-component film with colloidal particles could be inconvenient. A novel "swell-permeate" (SP) strategy was proposed to form homogeneous multi-component films. The SP strategy allows colloidal particles to fit into the polymer network by stretching the polymer chains assisted by water. We demonstrated the strategy by creating films with polysaccharide substrates as ß-cyclodextrin grafted chitosan (CS) with nanocellulose. The addition of nanocellulose significantly increased the mechanical properties and the barrier performance of the films. The size of nanocellulose particles in affecting mechanical properties was investigated by applying different length of cellulose nanocrystal (CNC), the longer of which, due to denser physical entanglements, showed a better increase to the film in the elastic modulus and tensile strength to 4.54-fold and 5.71-fold, respectively. The films were also loaded with ethyl-p-coumarate (EpCA) and had an enhanced performance in anti-microbial for Altenaria alternata, Salmonella typhi, and Escherichia coli. The anti-oxidative property was increased as well, and both effects were valid both in vitro and in ready-to-eat apples. The strategy provides a practical and convenient method for fabricating colloidal particle containing films, and the novel idea of "swell-permeate" is potentially regarded as a new solution to the challenge of ready-to-eat food quality maintenance.


Asunto(s)
Celulosa , Quitosano , Escherichia coli , Embalaje de Alimentos , Nanopartículas , Resistencia a la Tracción , Quitosano/química , Celulosa/química , Escherichia coli/efectos de los fármacos , Nanopartículas/química , Antibacterianos/química , Antibacterianos/farmacología , Antioxidantes/química , Antioxidantes/farmacología , beta-Ciclodextrinas/química , Películas Comestibles , Salmonella typhi/efectos de los fármacos , Módulo de Elasticidad
16.
Medicine (Baltimore) ; 103(36): e39489, 2024 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-39252273

RESUMEN

BACKGROUND: In patients with schizophrenia, Diankuang Mengxing Decoction with antipsychotics is one of the treatments for it. However, little information is available regarding the difference between the therapeutic effect of Diankuang Mengxing Decoction with antipsychotics and other treatments. Systematic evaluation is conducted to assess the efficacy and safety of Diankuang Mengxing Decoction and other antipsychotics, which are used to treat schizophrenia. METHODS: We performed a systematic review (PROSPERO ID: CRD42023414603). This entailed a computerized search of several research databases from their respective dates of establishment until April 11, 2023, which collected clinical randomized controlled trials of Diankuang Mengxing Decoction combined with antipsychotics. The databases that contributed to this study were PubMed, Web of Science, Embase, EBSCOhost, Cochrane, Scopus, and Google Scholar. Each publication was screened according to defined inclusion and exclusion criteria, and appropriate literature was extracted and evaluated for quality, for which meta-analysis was performed using RevMan 5.4. RESULTS: A literature review of 456 publications resulted in the inclusion of 18 randomized controlled trials with data collected from a total of 1636 patients. Meta-analytical results showed combination with risperidone, olanzapine, chlorpromazine, clozapine, ziprasidone, or aripiprazole increased the overall effectiveness of Diankuang Mengxing Decoction when treating schizophrenia (P < . 00001), among whom olanzapine demonstrated the greatest enhancement (Z = 3.65, odds ratio = 4.26, 95% CI: 1.96-9.28, P = .0003). The 4-week/30-day treatment (P = .0003) and a dosage of 400 mL/d of Diankuang Mengxing Decoction (P = .0004) were more effective. Also, there were widespread reductions to the Positive And Negative Syndrome Scale (PANSS) total scores, PANSS-positive symptom scores, PANSS-negative symptom scores, general psychopathology scores (P < .05 for all), as well as the incidence of adverse effects (Z = 2.79, odds ratio = 0.34, 95% CI: 0.16-0.73, P = .005) in patients with schizophrenia. CONCLUSION: The combination of Diankuang Mengxing Decoction with different antipsychotics can improve the overall prognosis of patients with schizophrenia; Diankuang Mengxing Decoction combined olanzapine, a dosage of 400 mL/d and a duration of 4 weeks/30 days being the best in this regard, by alleviating the symptoms and diminishing the disorder's adverse effects. To build on this work, more large-sample, multi-center, and high-quality clinical studies in the future would help to further validate our findings.


Asunto(s)
Antipsicóticos , Quimioterapia Combinada , Medicamentos Herbarios Chinos , Ensayos Clínicos Controlados Aleatorios como Asunto , Esquizofrenia , Esquizofrenia/tratamiento farmacológico , Humanos , Antipsicóticos/uso terapéutico , Antipsicóticos/efectos adversos , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/efectos adversos , Medicamentos Herbarios Chinos/administración & dosificación , Resultado del Tratamiento
17.
mBio ; : e0075624, 2024 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-39287444

RESUMEN

Phagocytosis of Mycobacterium tuberculosis (Mtb) followed by its integration into the matured lysosome is critical in the host defense against tuberculosis. How Mtb escapes this immune attack remains elusive. In this study, we unveiled a novel regulatory mechanism by which SIRT7 regulates cytoskeletal remodeling by modulating RAC1 activation. We discovered that SIRT7 expression was significantly reduced in CD14+ monocytes of TB patients. Mtb infection diminished SIRT7 expression by macrophages at both the mRNA and protein levels. SIRT7 deficiency impaired actin cytoskeleton-dependent macrophage phagocytosis, LC3II expression, and bactericidal activity. In a murine tuberculosis model, SIRT7 deficiency detrimentally impacted host resistance to Mtb, while Sirt7 overexpression significantly increased the host defense against Mtb, as determined by bacterial burden and inflammatory-histopathological damage in the lung. Mechanistically, we demonstrated that SIRT7 limits Mtb infection by directly interacting with and activating RAC1, through which cytoskeletal remodeling is modulated. Therefore, we concluded that SIRT7, in its role regulating cytoskeletal remodeling through RAC1, is critical for host responses during Mtb infection and proposes a potential target for tuberculosis treatment.IMPORTANCETuberculosis (TB), caused by Mycobacterium tuberculosis (Mtb), remains a significant global health issue. Critical to macrophages' defense against Mtb is phagocytosis, governed by the actin cytoskeleton. Previous research has revealed that Mtb manipulates and disrupts the host's actin network, though the specific mechanisms have been elusive. Our study identifies a pivotal role for SIRT7 in this context: Mtb infection leads to reduced SIRT7 expression, which, in turn, diminishes RAC1 activation and consequently impairs actin-dependent phagocytosis. The significance of our research is that SIRT7 directly engages with and activates Rac Family Small GTPase 1 (RAC1), thus promoting effective phagocytosis and the elimination of Mtb. This insight into the dynamic between host and pathogen in TB not only broadens our understanding but also opens new avenues for therapeutic development.

19.
Zhongguo Zhong Yao Za Zhi ; 49(16): 4387-4395, 2024 Aug.
Artículo en Chino | MEDLINE | ID: mdl-39307775

RESUMEN

Aconitum vilmorinianum is an authentic and superior medicinal herbal in Yunnan, which is rich in yunaconitine and other diterpene alkaloids. Diterpene alkaloids are its main active components. Farnesyl pyrophosphate synthase(FPS) is a key enzyme in the terpene biosynthetic pathway and plays an important role in diterpene alkaloid biosynthesis. Functional studies of FPS help to reveal the molecular mechanism of diterpene alkaloid biosynthesis. In this study, one FPS gene(AvFPS) was selected based on the transcriptome data of A. vilmorinianum. Its full-length sequence was cloned, and bioinformatic analysis, functional verification, and gene expression analysis were performed. The open reading frame(ORF) of AvFPS was 1 056 bp, encoding 351 amino acids. Its molecular weight was 41 kDa. AvFPS had two typical conserved functional domains of isopentenyl transferase, " DDIMD" and " DDYXD". The recombinant protein of AvFPS was expressed in Escherichia coli, and purified recombinant protein was used for in vitro enzymatic reaction. The results revealed that AvFPS was able to catalyze the synthesis of farnesyl pyrophosphate(FPP). The results of qRT-PCR analysis showed that AvFPS was expressed in the roots, stems, leaves, and flowers of A. vilmorinianum, with the highest expression level in the roots. The expression level of AvFPS was significantly up-regulated by MeJA induction. This study clarified the catalytic function of AvFPS, revealed the expression pattern of AvFPS in different tissue, as well as at different time induced by MeJA, and provided a reference for a deeper understanding of the function of FPS in the biosynthesis of diterpenoid components.


Asunto(s)
Aconitum , Clonación Molecular , Geraniltranstransferasa , Proteínas de Plantas , Geraniltranstransferasa/genética , Geraniltranstransferasa/metabolismo , Geraniltranstransferasa/química , Aconitum/genética , Aconitum/enzimología , Aconitum/química , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Proteínas de Plantas/química , Regulación de la Expresión Génica de las Plantas , Secuencia de Aminoácidos , Filogenia , Alineación de Secuencia
20.
J Environ Manage ; 370: 122440, 2024 Sep 18.
Artículo en Inglés | MEDLINE | ID: mdl-39299103

RESUMEN

As industrial and agricultural production depends on water supply, it is crucial for economic development. The available freshwater reserves on Earth are insufficient to meet humanity's growing demands. This study establishes a three-stage anoxic/oxic (A/O)-moving bed biofilm reactor (MBBR) system. The study evaluated the wastewater purification capacity of the system in summer and winter, examined the system's removal efficiency of 10 pharmaceuticals and personal care products (PPCPs) from the water, and analyzed the composition of microbial communities. Results indicate that the system effectively removes pollutants and PPCPs, with the aerobic tanks in the first two A/O stages playing a significant role in PPCP removal. The system is effective in removing four kinds of pollutants: AMP, IBU, CLR, and CAF, and the removal efficiency of CAF is up to 99.2%. Seasonal variations significantly affect the removal of PPCPs and bacterial growth, leading to changes in bacterial species. At the genus level, 41 bacterial types presented different effects in response to temperature changes, with Trichoderma and c_OM190_unclassified being the most affected. This study provides essential theoretical support for reducing pollutant levels and improving water recycling and economic efficiency.

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