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1.
Front Endocrinol (Lausanne) ; 15: 1435102, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39359414

RESUMO

Background: It is challenging for clinicians to distinguish adrenocortical carcinoma (ACC) from benign adrenocortical adenomas (ACA) in their early stages. This study explored the value of serum steroid profiling as a complementary biomarker for malignancy diagnosis of ACC other than diameter and explored the influence of sex and functional status. Methods: In this retrospective study, a matched cohort of patients diagnosed with either ACC or ACA based on histopathology was meticulously paired in a 1:1 ratio according to sex, age, and functional status. Eight serum steroids including 11-deoxycortisol, 11-deoxycorticosterone, progesterone, androstenedione, dehydroepiandrosterone (DHEA), dehydroepiandrosterone sulfate (DHEAS), 17-hydroxyprogesterone, and estradiol, were quantified by liquid chromatography tandem mass spectrometry. We conducted a comparative analysis of the clinical characteristics and serum steroid profiles of patients with ACC and ACA, with further subgroup analysis. Results: The study included 31 patients with ACC and 31 matched patients with ACA. Patients with ACC exhibited significantly larger tumor diameters, lower body mass index (BMI), and higher levels of 11-deoxycortisol, progesterone, and androstenedione than those with ACA. 11-deoxycortisol was the only valuable index for discriminating ACC from ACA, regardless of functional status and sex. Progesterone, DHEA, and DHEAS levels were higher in the functional ACC group than in the non-functional ACC group. Female ACC patients, especially in postmenopausal female exhibited higher levels of androstenedione than male patients. The area under the curve of tumor diameter, 11-deoxycortisol, and BMI was 0.947 (95% CI 0.889-1.000), with a sensitivity of 96.8% and specificity of 90.3%. Conclusion: Serum steroid profiling serves as a helpful discriminative marker for ACC and ACA, with 11-deoxycortisol being the most valuable marker. For other steroid hormones, consideration of sex differences and functional status is crucial.


Assuntos
Neoplasias do Córtex Suprarrenal , Adenoma Adrenocortical , Carcinoma Adrenocortical , Humanos , Masculino , Feminino , Neoplasias do Córtex Suprarrenal/sangue , Neoplasias do Córtex Suprarrenal/diagnóstico , Neoplasias do Córtex Suprarrenal/patologia , Carcinoma Adrenocortical/sangue , Carcinoma Adrenocortical/diagnóstico , Pessoa de Meia-Idade , Estudos Retrospectivos , Adenoma Adrenocortical/sangue , Adenoma Adrenocortical/diagnóstico , Adenoma Adrenocortical/patologia , Adulto , Esteroides/sangue , Diagnóstico Diferencial , Idoso , Biomarcadores Tumorais/sangue , Fatores Sexuais
3.
Diabetes Metab Syndr Obes ; 17: 3249-3265, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39247430

RESUMO

Purpose: Preventing and treating diabetic nephropathy (DN) are global challenges due to the complexity and diversity of its causes and manifestations. It is important to find effective medications to treat DN. Patients and Methods: Gene expression files of DN were downloaded from the GEO database to identify the differentially expressed genes. Network pharmacology and molecular docking were used to explore the possible mechanisms of modified Buyang Huanwu Decoction (mBHD) in treating DN. Biochemical, histopathological, and real-time PCR analyses were conducted in both in vivo and in vitro DN models to investigate the effects of mBHD. Results: A total of 336 active ingredients and 124 potential targets of mBHD associated with DN were identified. Among them, 8 hub genes were found to be important targets for mBHD in treating DN and were significantly correlated with the infiltration status of six immune cells. Partially, the active ingredients of mBHD demonstrated good stability in binding to CASP3 and TP53. mBHD treatment significantly reduced levels of total cholesterol, triglyceride, blood urea nitrogen, serum creatinine, and microalbumin in db/db mice. HE and Masson's staining results showed that mBHD attenuated renal injury in db/db mice. Additionally, mBHD treatment could significantly alter the expression of CASP3, CCL2, TP53, ALB, and HMOX1. Conclusion: mBHD may be involved in the treatment of DN through multiple ingredients, targets, and pathways. In addition, mBHD could alleviate renal injury in db/db mice, possibly involving CASP3, CCL2, TP53, ALB, and HMOX1.

4.
Artigo em Inglês | MEDLINE | ID: mdl-39307933

RESUMO

BACKGROUND: Sex differences in blood pressure (BP) levels and hypertension are important and the role of socioeconomic status (SES) in sex differences of hypertension remains unclear. OBJECTIVE: We aimed to evaluate the impact of SES on sex differences of hypertension in a nationally representative survey study. METHODS: A total of 98,658 participants aged ≥18 years who have lived in their current residence for ≥6 months were recruited from 162 study sites across mainland China. Sex was self-reported. Individual-level SES included the highest level of education and annual household income. Area-level SES included economic development status, urban/rural residency, and north/south location. Outcomes included levels of systolic and diastolic BP, and hypertension. Linear and Cox regression models were used to examine the associations between sex (women vs. men) and BP characteristics stratified by individual or combined SES indicators. RESULTS: Systolic and diastolic BP levels and prevalence of hypertension were higher in men than women. This sex difference was found across categories of SES with widened sex disparities in participants having more favorable SES. Significant multiplicative interaction effects of SES on the association of sex with BP characteristics were found. Women with improving SES were associated with lower BP and hypertension prevalence compared with men. For combined SES, a 9% (prevalence ratio (PR)=0.91, 95% confidence interval (CI)=0.83, 0.98) and a 30% lower probability (PR=0.70, 95% CI=0.63, 0.78) of having hypertension were found in women with an overall intermediate SES and high SES, respectively compare with low SES while no significant reduction was found in men. CONCLUSIONS: There are significant sex differences in BP characteristics and SES has a potent impact on the disparities. Sex-specific public health policies to alleviate socioeconomic inequalities, especially in women are important for the prevention of hypertension.

5.
Medicine (Baltimore) ; 103(37): e39706, 2024 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-39287255

RESUMO

Recent observational studies have indicated that psychiatric disorders were associated with risk of bone mineral density (BMD) reduction. But the causal relationship between neuroticism and BMD remained unclear. By using public genome-wide association study data, a 2-sample bidirectional Mendelian randomization (MR) study was performed to investigate the causal relationship between neuroticism and BMD (heel BMD, forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD). Inverse-variance weighted, weighted median, and MR-Egger were used to assess the causal effects. Multiple sensitivity analyses were conducted to assess the potential bias of the causal estimates. Multivariable MR analysis was used to assess the direct causal effects of neuroticism on BMD with adjustment of common risk factors of BMD reduction. Univariable MR analysis indicated that genetically predicted higher neuroticism was significantly associated with an increased risk of heel BMD reduction (inverse-variance weighted ß = -0.039; se = 0.01; P = .0001; Bonferroni-corrected P = .0005) but not with other BMD (forearm BMD, femoral neck BMD, lumbar spine BMD, and total body BMD) potentially due to limited statistical power. The causal effects remained significant after accounting for the effects of body mass index, smoking, and drinking. Genetic proxy for higher neuroticism was significantly associated with an increased risk of heel BMD reduction. Further studies were warranted to elucidate the underlying biological mechanisms and explore the potential application in disease early screening and management.


Assuntos
Densidade Óssea , Estudo de Associação Genômica Ampla , Análise da Randomização Mendeliana , Neuroticismo , Humanos , Densidade Óssea/genética , Fatores de Risco , Feminino , Polimorfismo de Nucleotídeo Único , Masculino
6.
BMC Nurs ; 23(1): 608, 2024 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-39218861

RESUMO

OBJECTIVE: The purpose of this study is to construct an organ system-centered undergraduate nursing professional training model and explore its application effect. METHODS: This study is divided into two steps. In the early stage, literature review and expert consultation were used to establish the training mode (curriculum and assessment standard) of nursing undergraduate specialty based on organ system reform. Secondly, a cross-sectional survey method was used to investigate the training quality of nursing students who graduated from Jinzhou Medical University from 2007 to 2017 under this model. RESULTS: A five-module curriculum system was established, including general courses, public basic courses, professional education courses, expanding elective courses and concentrated practical teaching. Under the teaching reform of organ system, the nursing graduates of Jinzhou Medical University, who are mainly employed in public hospitals, are generally not satisfied with their jobs, salaries, contents and prospects. Their overall satisfaction with their alma mater is very high; Graduates have certain independent core competence; Employers are basically satisfied with graduates. CONCLUSION: The training mode of undergraduate nursing specialty based on organ system reform basically meets the training requirements and objectives.

7.
Polymers (Basel) ; 16(18)2024 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-39339043

RESUMO

Nowadays, there has been an increasing research interest into N-halamine compounds due to their wide antimicrobial properties and no drug resistance. Most of the research mainly focuses on small molecular N-halamines, while few studies are on macromolecule N-halamines. In this work, antibacterial N-halamine polymer materials based on proteins (GS-Cl) were synthesized with an antibacterial component of oxidative chlorine, a support component of a gelatin sponge. After carrying out systematic characterization, the GS-Cls exhibited well-defined porous morphology and had a high efficiency in the killing of Gram-positive bacteria (E. coli) and Gram-negative bacteria (S. aureus). The loading of oxidative chlorine (Cl+%) could be controlled by changing the NaClO concentrations and chlorination times. The biocompatibility was confirmed as well. In vivo experiments suggested that the GS-Cl sample could effectively promote the healing of skin wounds in mice E. coli and S. aureus infection models. These studies show that proteins can be chlorinated and endowed with antimicrobial properties, which has great application potential in the treatment of bacteria-infected wounds.

8.
Discov Oncol ; 15(1): 502, 2024 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-39331271

RESUMO

OBJECTIVE: The purpose of this research was to investigate how different types of immune cells impact the outlook of individuals with breast cancer, as well as identify the essential genes associated with immune cell subtype enrichment. METHODS: The Cancer Genome Atlas (TCGA) database and Gene Expression Omnibus (GEO) database were used to obtain global transcriptome sequencing data sets of breast tissue. The study utilized the CIBERSORT algorithm to determine the presence of 22 different types of immune cells in both breast cancer tissue and normal breast tissue.Immune cell infiltration content was utilized to conduct univariate COX analysis in order to identify risk factors linked to breast cancer prognosis. RESULTS: Univariate COX analysis indicates that Macrophages M1 and B cells naive are beneficial factors for the outlook of individuals with breast cancer (P < 0.05), while Macrophages M2 and Monocytes are detrimental factors for the prognosis of breast cancer patients (P < 0.05). The high infiltration group of macrophage M2 had a poorer prognosis compared to the low infiltration group (P < 0.001); Conversely, the high infiltration group of macrophage M1 had a better prognosis than the low infiltration group (P = 0.002). CONCLUSION: The study provided an overview of immune cell infiltration in breast cancer tissues, identifying macrophage M1 and macrophage M2 as potential factors in breast cancer development and progression. Additionally, genes associated with macrophage phenotype were analyzed, offering insights into macrophage polarization mechanisms.

9.
Womens Health Rep (New Rochelle) ; 5(1): 453-460, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39206020

RESUMO

Objective: Preeclampsia is a serious pregnancy complication that jeopardizes the health of both the mother and the fetus. Platelet parameters are closely linked to the severity of preeclampsia. This study aimed to assess the diagnostic potential of platelet parameters in the early second trimester for the detection of preeclampsia. Methods: A total of 840 participants from the Affiliated Hospital of Jining Medical College were included in the study, consisting of 327 healthy pregnant women, 209 with mild preeclampsia, and 304 with severe preeclampsia. General clinical data and platelet parameters for these three groups of pregnant women were collected, and differences among them were compared. In addition, univariate analysis and logistic regression were used to identify preeclampsia risk factors, and receiver operating characteristic curve analysis was conducted to assess the predictive value of platelet parameters. Results: Platelet count was not found to significantly differ between the healthy and preeclampsia groups. However, mean platelet volume, platelet distribution width (PDW), and platelet-large cell ratios (P-LCR) were observed to be significantly higher in the preeclampsia group than the healthy group. After adjusting for confounding factors (such as age, gestational week at blood sampling, systolic and diastolic blood pressure, and body mass index during the second trimester), it was determined that PDW and P-LCR could be considered effective predictors of preeclampsia. Conclusion: In clinical practice, P-LCR and PDW hold potential predictive value for preeclampsia.

10.
BMC Public Health ; 24(1): 2201, 2024 Aug 13.
Artigo em Inglês | MEDLINE | ID: mdl-39138460

RESUMO

BACKGROUND: To investigate the cross-sectional and longitudinal associations between depressive symptoms and the prevalence of frailty and its components in a nationally representative sample of middle-aged and older Chinese adults. METHOD: The China Health and Retirement Longitudinal Study (CHARLS) provided data on 2581 (after inclusion and exclusion criteria) adults aged ≥ 45 years. Every two years, face-to-face, computer-aided personal interviews (CAPI), and structured questionnaires were used to follow up with the respondents. The Chinese version of the Center for Epidemiologic Studies-Depression Scale (CES-D) was used to evaluate depressive symptoms, and the Fried criteria were used to measure frailty. The odds ratio (OR) and 95% confidence interval (CI) for the association of exposure (depressive symptoms at baseline) with the onset of the outcome (frailty and its components) in the individuals at baseline were analyzed by binary logistic regression. RESULTS: At baseline, 11.62% of participants had frailty, and 57.92% had depressive symptoms. In the cross-sectional analysis, depressive symptoms (OR = 5.222, 95%CI 3.665-7.442) were associated with frailty. In the longitudinal analysis, after adjusting for the full set of covariates among participants free of baseline frailty, depressive symptoms were significantly associated with incident frailty during the short term (OR = 2.193, 95%CI 1.324-3.631) and the long term (OR = 1.926, 95%CI 1.021-3.632). Meanwhile, depressive symptoms were associated with an increased risk of weakness (OR = 1.990, 95%CI 1.250-3.166), slowness (OR = 1.395, 95%CI 1.044-1.865), and exhaustion (OR = 2.827, 95%CI 2.150-3.719) onset during the short-term. Depressive symptoms were associated with an increased risk of exhaustion (OR = 2.869, 95%CI 2.004-4.109) onset during the long-term. CONCLUSION: Among middle-aged and older adults, depressive symptoms could predict frailty during 2 years of follow-up and 4 years of follow-up. When considering potential confounding factors, depressive symptoms were considered a predictor of weakness, slowness, and exhaustion. Interventions aimed at preventing depressive symptoms may be beneficial in reducing frailty and its components.


Assuntos
Depressão , Fragilidade , Humanos , Estudos Longitudinais , Masculino , Feminino , Depressão/epidemiologia , Pessoa de Meia-Idade , Idoso , China/epidemiologia , Fragilidade/epidemiologia , Fragilidade/psicologia , Estudos Transversais , Prevalência , Idoso Fragilizado/estatística & dados numéricos , Idoso Fragilizado/psicologia , Idoso de 80 Anos ou mais , Inquéritos e Questionários
11.
Clinics (Sao Paulo) ; 79: 100436, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39096856

RESUMO

This study aimed to perform exhaustive bioinformatic analysis by using GSE29221 micro-array maps obtained from healthy controls and Type 2 Diabetes (T2DM) patients. Raw data are downloaded from the Gene Expression Omnibus database and processed by the limma package in R software to identify Differentially Expressed Genes (DEGs). Gene ontology functional analysis and Kyoto Gene Encyclopedia and Genome Pathway analysis are performed to determine the biological functions and pathways of DEGs. A protein interaction network is constructed using the STRING database and Cytoscape software to identify key genes. Finally, immune infiltration analysis is performed using the Cibersort method. This study has implications for understanding the underlying molecular mechanism of T2DM and provides potential targets for further research.


Assuntos
Biologia Computacional , Diabetes Mellitus Tipo 2 , Perfilação da Expressão Gênica , Humanos , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/imunologia , Mapas de Interação de Proteínas/genética , Redes Reguladoras de Genes/genética , Ontologia Genética , Bases de Dados Genéticas , Estudos de Casos e Controles
12.
Behav Brain Res ; 472: 115149, 2024 08 24.
Artigo em Inglês | MEDLINE | ID: mdl-39013529

RESUMO

The microbiome-gut-brain axis is related to schizophrenia (SCZ). The role of intestinal mycobiota in SCZ has been under investigated. We present a half-year follow-up study involving 109 chronic SCZ patients and 77 healthy controls. Intestinal mycobiota was tested by internal transcribed spacer (ITS). Untargeted liquid chromatography-mass spectrometry (LC-MS) was used to measure fecal metabolites. Symptom severity was assessed using the Positive and Negative Syndrome Scale. Enterotype analysis showed that Candida-type patients exhibited severer positive symptoms and depression factors than Saccharomyces-type patients. Candida and its top species and operational taxonomic units (OTUs) were positively correlated with depression factors (all p=0.001). Fecal metabolites analysis showed that upregulated metabolites were associated with chronic inflammation (NF-κB pathway and T helper cell differentiation), downregulated metabolites were associated with glutamate metabolism, serotonergic and dopaminergic synapse. Procrustes analysis revealed significant correlation between intestinal mycobiota and fecal metabolites (M2=0.937, p<0.001). Metabolic module analysis showed that the top module, MEturquoise (associated with Th1 and Th2 cell differentiation), was negatively correlated with SCZ (r=-0.783, p<0.0001), positively correlated with Candida, Aspergillus, Trichosporon and Talaromyces (decreased in SCZ) and negatively correlated with Saccharomyces (increased in SCZ). We also found impairments of intestinal barrier in SCZ, characterized by increased in blood D-lactate (mucosa impairment marker) and decreased in blood mucin 2 (mucosal barrier protective protein). Serum levels of TNF-α was increased and showed stable high levels during treatment. This study suggests that mycobiota dysbiosis-related chronic inflammation and an impaired intestinal mucosal barrier are associated with chronic SCZ.


Assuntos
Disbiose , Fezes , Microbioma Gastrointestinal , Inflamação , Esquizofrenia , Humanos , Disbiose/microbiologia , Disbiose/metabolismo , Microbioma Gastrointestinal/fisiologia , Masculino , Esquizofrenia/metabolismo , Esquizofrenia/microbiologia , Esquizofrenia/imunologia , Feminino , Adulto , Pessoa de Meia-Idade , Fezes/microbiologia , Inflamação/metabolismo , Inflamação/microbiologia , Seguimentos , Doença Crônica , Candida , Eixo Encéfalo-Intestino/fisiologia
13.
J Integr Neurosci ; 23(7): 127, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-39082295

RESUMO

BACKGROUND: This meta-analysis explores alterations in the gut microbiota of patients with Multiple Sclerosis (MS) using 16S ribosomal RNA (rRNA) gene sequencing. METHODS: Adhering to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, our comprehensive review spanned major databases, including PubMed, Web of Science, Embase, Cochrane, and Ovid, targeting observational studies that implemented 16S rRNA gene sequencing on fecal specimens. The quality of these studies was meticulously evaluated using the Newcastle-Ottawa scale. RESULTS: Our search yielded 26 relevant studies conducted between 2015-2022, encompassing 2885 participants. No significant differences were observed in alpha diversity indices (Shannon, Chao1, Operational Taxonomic Units (OTU), and Simpson) between MS patients and controls in general. Nonetheless, subgroup analyses according to disease activity using the Shannon index highlighted a significant decrease in microbial diversity during MS's active phase. Similarly, an evaluation focusing on MS phenotype revealed diminished diversity in individuals with relapsing-remitting MS (RRMS). Microbial composition analysis revealed no consistent increase in pro-inflammatory Bacteroidetes or decrease in anti-inflammatory Firmicutes within the MS cohort. CONCLUSION: The gut microbiome's role in MS presents a complex panorama, where alterations in microbial composition might hold greater significance to disease mechanisms than diversity changes. The impact of clinical factors such as disease activity and phenotype are moderately significant, underscoring the need for further research to elucidate these relationships. Prospective research should employ longitudinal methodologies to elucidate the chronological interplay among gut microbiota, disease evolution, and therapeutic strategies.


Assuntos
Microbioma Gastrointestinal , Esclerose Múltipla , RNA Ribossômico 16S , Humanos , RNA Ribossômico 16S/análise , Esclerose Múltipla/microbiologia
14.
Sci Total Environ ; 948: 174595, 2024 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-38986695

RESUMO

China is experiencing large-scale rural-urban migration and rapid urbanization, which have had significant impact on terrestrial carbon sink. However, the impact of rural-urban migration and its accompanying urban expansion on the carbon sink is unclear. Based on multisource remote sensing product data for 2000-2020, the soil microbial respiration equation, relative contribution rate, and threshold analysis, we explored the impact of rural depopulation on the carbon sink and its threshold. The results revealed that the proportion of the rural population in China decreased from 63.91 % in 2000 to 36.11 % in 2020. Human pressure decreased by 1.82% in rural depopulation areas, which promoted vegetation restoration in rural areas (+8.45 %) and increased the carbon sink capacity. The net primary productivity (NPP) and net ecosystem productivity (NEP) of the vegetation in the rural areas increased at rates of 2.95 g C m-2 yr-1 and 2.44 g C m-2 yr-1. Strong rural depopulation enhanced the carbon sequestration potential, and the NEP was 1.5 times higher in areas with sharp rural depopulation than in areas with mild rural depopulation. In addition, the rural depopulation was accompanied by urban expansion, and there was a positive correlation between the comprehensive urbanization level (CUL) and NEP in 75.29 % of urban areas. In the urban areas, the vegetation index increased by 88.42 %, and the urban green space partially compensated for the loss of carbon sink caused by urban expansion, with a growth rate of 4.96 g C m-2 yr-1. Changes in rural population have a nonlinear impact on the NEP. When the rural population exceeds 545.686 people/km2, an increase in the rural population will have a positive impact on the NEP. Our research shows that rural depopulation offers a potential opportunity to restore natural ecosystems and thus increase the carbon sequestration capacity.


Assuntos
Sequestro de Carbono , Ecossistema , Urbanização , China , População Rural , Monitoramento Ambiental
15.
Trials ; 25(1): 490, 2024 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-39030637

RESUMO

BACKGROUND: The high recurrence rate after liver resection emphasizes the urgent need for neoadjuvant therapy in hepatocellular carcinoma (HCC) to enhance the overall prognosis for patients. Immune checkpoint inhibitors, camrelizumab combined with an anti-angiogenic tyrosine kinase inhibitor (TKI) apatinib, have emerged as a first-line treatment option for patients with unresectable HCC, yet its neoadjuvant application in combination with transarterial chemoembolization (TACE) in HCC remains unexplored. Therefore, this study aims to investigate the efficacy and safety of sequential TACE, camrelizumab, and apatinib as a neoadjuvant therapy for single, huge HCC. METHODS: This multi-center, open-label randomized phase 3 trial will be conducted at 7 tertiary hospitals. Patients with single huge (≥ 10 cm in diameter), resectable HCC will be randomly assigned in a 1:1 ratio to arm of surgery alone or arm of neoadjuvant therapy followed by surgery. In the neoadjuvant therapy group, patients will receive TACE within 1 week after randomization, followed by camrelizumab (200 mg q2w, 4 cycles), along with apatinib (250 mg qd, 2 months). Patients will receive liver resection after neoadjuvant therapy unless the disease is assessed as progressive. The primary outcome is recurrence-free survival (RFS) at 1 year. The planned sample size of 60 patients will be calculated to permit the accumulation of sufficient RFS events in 1 year to achieve 80% power for the RFS primary endpoint. DISCUSSION: Synergistic effects provided by multimodality therapy of locoregional treatment, TKI, and anti-programmed cell death 1 inhibitor significantly improved overall survival for patients with unresectable HCC. Our trial will investigate the efficacy and safety of the triple combination of TACE, camrelizumab, and apatinib as a neoadjuvant strategy for huge, resectable HCC. TRIAL REGISTRATION: www.chitr.org.cn ChiCTR2300078086. Registered on November 28, 2023. Start recruitment: 1st January 2024. Expected completion of recruitment: 15th June 2025.


Assuntos
Anticorpos Monoclonais Humanizados , Carcinoma Hepatocelular , Quimioembolização Terapêutica , Neoplasias Hepáticas , Terapia Neoadjuvante , Piridinas , Humanos , Carcinoma Hepatocelular/terapia , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/mortalidade , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/terapia , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/mortalidade , Neoplasias Hepáticas/tratamento farmacológico , Quimioembolização Terapêutica/efeitos adversos , Quimioembolização Terapêutica/métodos , Piridinas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/efeitos adversos , Anticorpos Monoclonais Humanizados/uso terapêutico , Anticorpos Monoclonais Humanizados/administração & dosagem , Anticorpos Monoclonais Humanizados/efeitos adversos , Terapia Neoadjuvante/efeitos adversos , Ensaios Clínicos Controlados Aleatórios como Assunto , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Protocolos de Quimioterapia Combinada Antineoplásica/efeitos adversos , Masculino , Hepatectomia , Adulto , Pessoa de Meia-Idade , Estudos Multicêntricos como Assunto , Ensaios Clínicos Fase III como Assunto , Feminino , Resultado do Tratamento , China , Idoso
16.
J Ethnopharmacol ; 333: 118469, 2024 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-38914151

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Yishen Gushu Formula (YSGSF) is composed of Epimedium, prepared Rehmannia, Drynaria, Eucommia, Dodder, ginseng, Astragalus, Ligusticum wallichii, Aucklandia and Panax notoginseng. It can improve bone mineral density by regulating bone metabolism. However, the mechanism of YSGSF in the treatment of Postmenopausal osteoporosis (PMOP) remains unclear. AIM OF THE STUDY: The compounds, targets, and molecular mechanisms of YSGSF in the treatment of PMOP were investigated using broad-spectrum target metabolomics from plants, combined with network pharmacology and animal studies, leading to a discussion on a novel approach to understanding YSGSF's action in PMOP treatment. MATERIALS AND METHODS: Using ultra-performance liquid chromatography coupled with triple quadrupole-linear ion trap tandem mass spectrometry (UPLC-QTRAP-MS/MS) within a comprehensive targeted metabolomics framework, the active constituents of YSGSF were identified. This, alongside network pharmacology and molecular docking, facilitated the identification of critical signaling pathways and targets pertinent to YSGSF's therapeutic effect on PMOP. Subsequently, an animal model for PMOP was developed. Following intervention grouping, rats' weight changes were recorded; serum bone metabolic factors were assessed via ELISA; bone microstructure was examined using HE staining and Micro-CT; and key signaling pathway proteins and genes were analyzed through immunohistochemistry to validate YSGSF's potential mechanism in PMOP treatment. RESULTS: A total of 84 main active components of YSGSF were identified. The key signaling pathways affected by YSGSF in the treatment of PMOP were the TNF and IL-7 signaling pathways, closely related to TNF-α, IL-1ß, c-jun and other protein targets. The results of animal experiments showed that YSGSF could downregulate the expression of TNF-a, IL-1ß and c-Jun proinflammatory factors by regulating the TNF and IL-7 signaling pathways and regulate the inflammatory response, osteocyte differentiation and apoptosis to control the development of PMOP. CONCLUSION: YSGSF activates the TNF-α and IL-7 signaling pathways in PMOP rats, reducing TNF-α and IL-1ß levels, the c-Jun inflammatory response, and osteocyte differentiation and apoptosis, thus playing a significant role in treating PMOP.


Assuntos
Medicamentos de Ervas Chinesas , Metabolômica , Farmacologia em Rede , Osteoporose Pós-Menopausa , Ratos Sprague-Dawley , Animais , Feminino , Medicamentos de Ervas Chinesas/farmacologia , Osteoporose Pós-Menopausa/tratamento farmacológico , Ratos , Modelos Animais de Doenças , Simulação de Acoplamento Molecular , Densidade Óssea/efeitos dos fármacos , Ovariectomia , Humanos , Espectrometria de Massas em Tandem , Transdução de Sinais/efeitos dos fármacos
17.
Pract Lab Med ; 40: e00414, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38939102

RESUMO

Background: Most glycated hemoglobin A1c (HbA1c) analytical reagents used were obtained from the analyzer's manufacturer. However, clinical laboratories need more choices for HbA1c analytical reagents to overcome the limitations of dedicated reagents for special analyzers. We developed new mobile phase buffers as HbA1c diagnostic reagents and evaluated their analytical performance for the HbA1c assay. Methods: Different mobile phase buffers used as HbA1c diagnostic reagents were prepared using different concentrations of sodium salts. According to the Clinical and Laboratory Standards Institute (CLSI) recommendation guidelines, the analytical performances of the newly developed mobile phase buffers were evaluated on an ARKRAY HA-8160 Analyzer. Both quality controls and clinical blood samples were used in these experiments. To assess the quality of the newly developed mobile phase buffers, precision, accuracy, linearity, carryover, interference, bias, correlation with commercial reagents, and stability were analyzed. Results: The CVs of intra-assay precision and interassay precision of quality control and clinical.There were fewer than 1.00 % blood sample assays using the newly developed mobile phase buffer. The RDs of accuracy were less than 1.00 %. Linearity: R2 = 0.9998 in the concentration range of 4.40%-17.30 %. Carryover: 0.00 %. Reagent comparison revealed that the Pearson regression equation was Y = 0.9884x+0.05692 (R2 = 0.9977), and the Bland-Altman mean difference was -0.02650 % (CI: -0.2121 %-0.1591 %) between the two analytical reagents. Stability was also acceptable within 12 months. This mobile phase buffer showed good anti-interference ability. Conclusion: The newly developed mobile phase buffers demonstrated good analytical performance and were suitable for clinical HbA1c assays on an ARKRAY HA-8160 Analyzer.

18.
Compr Rev Food Sci Food Saf ; 23(4): e13397, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38924311

RESUMO

Fungal infections of fresh fruits and vegetables (FFVs) can lead to safety problems, including consumer poisoning by mycotoxins. Various strategies exist to control fungal infections of FFVs, but their effectiveness and sustainability are limited. Recently, new concepts based on the microbiome and pathobiome have emerged and offer a more holistic perspective for advancing postharvest pathogen control techniques. Understanding the role of the microbiome in FFV infections is essential for developing sustainable control strategies. This review examines current and emerging approaches to postharvest pathology. It reviews what is known about the initiation and development of infections in FFVs. As a promising concept, the pathobiome offers new insights into the basic mechanisms of microbial infections in FFVs. The underlying mechanisms uncovered by the pathobiome are being used to develop more relevant global antifungal strategies. This review will also focus on new technologies developed to target the microbiome and members of the pathobiome to control infections in FFVs and improve safety by limiting mycotoxin contamination. Specifically, this review stresses emerging technologies related to FFVs that are relevant for modifying the interaction between FFVs and the microbiome and include the use of microbial consortia, the use of genomic technology to manipulate host and microbial community genes, and the use of databases, deep learning, and artificial intelligence to identify pathobiome markers. Other approaches include programming the behavior of FFVs using synthetic biology, modifying the microbiome using sRNA technology, phages, quorum sensing, and quorum quenching strategies. Rapid adoption and commercialization of these technologies are recommended to further improve the overall safety of FFVs.


Assuntos
Frutas , Verduras , Frutas/microbiologia , Verduras/microbiologia , Fungos , Microbiota , Antifúngicos/farmacologia , Doenças das Plantas/microbiologia , Doenças das Plantas/prevenção & controle , Micotoxinas
19.
PLoS One ; 19(6): e0305571, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38885281

RESUMO

Congenital heart disease (CHD) is the most serious form of heart disease, and chronic hypoxia is the basic physiological process underlying CHD. Some patients with CHD do not undergo surgery, and thus, they remain susceptible to chronic hypoxia, suggesting that some protective mechanism might exist in CHD patients. However, the mechanism underlying myocardial adaptation to chronic hypoxia remains unclear. Proteomics was used to identify the differentially expressed proteins in cardiomyocytes cultured under hypoxia for different durations. Western blotting assays were used to verify protein expression. A Real-Time Cell Analyzer (RTCA) was used to analyze cell growth. In this study, 3881 proteins were identified by proteomics. Subsequent bioinformatics analysis revealed that proteins were enriched in regulating oxidoreductase activity. Functional similarity cluster analyses showed that chronic hypoxia resulted in proteins enrichment in the mitochondrial metabolic pathway. Further KEGG analyses found that the proteins involved in fatty acid metabolism, the TCA cycle and oxidative phosphorylation were markedly upregulated. Moreover, knockdown of CPT1A or ECI1, which is critical for fatty acid degradation, suppressed the growth of cardiomyocytes under chronic hypoxia. The results of our study revealed that chronic hypoxia activates fatty acid metabolism to maintain the growth of cardiomyocytes.


Assuntos
Ácidos Graxos , Miócitos Cardíacos , Proteômica , Proteômica/métodos , Miócitos Cardíacos/metabolismo , Ácidos Graxos/metabolismo , Animais , Hipóxia Celular , Adaptação Fisiológica , Ratos , Miocárdio/metabolismo , Miocárdio/patologia , Hipóxia/metabolismo , Proliferação de Células , Carnitina O-Palmitoiltransferase/metabolismo , Carnitina O-Palmitoiltransferase/genética
20.
Mol Nutr Food Res ; 68(10): e2300871, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38704749

RESUMO

SCOPE: Prenatal nutrition imbalance correlates with developmental origin of cardiovascular diseases; however whether maternal high-sucrose diet (HS) during pregnancy causes vascular damage in renal interlobar arteries (RIA) from offspring still keeps unclear. METHODS AND RESULTS: Pregnant rats are fed with normal drinking water or 20% high-sucrose solution during the whole gestational period. Swollen mitochondria and distributed myofilaments are observed in vascular smooth muscle cells of RIA exposed to prenatal HS. Maternal HS increases phenylephrine (PE)-induced vasoconstriction in the RIA from adult offspring. NG-Nitro-l-arginine (L-Name) causes obvious vascular tension in response to PE in offspring from control group, not in HS. RNA-Seq of RIA is performed to reveal that the gene retinoid X receptor g (RXRg) is significantly decreased in the HS group, which could affect vascular function via interacting with PPARγ pathway. By preincubation of RIA with apocynin (NADPH inhibitor) or capivasertib (Akt inhibitor), the results indicate that ROS and Akt are the vital important factors to affect the vascular function of RIA exposure to prenatal HS. CONCLUSION: Maternal HS during the pregnancy increases PE-mediated vasoconstriction of RIA from adult offspring, which is mainly related to the enhanced Akt and ROS regulated by the weakened PPARγ-RXRg.


Assuntos
Efeitos Tardios da Exposição Pré-Natal , Transdução de Sinais , Vasoconstrição , Animais , Feminino , Masculino , Gravidez , Ratos , Sacarose Alimentar/efeitos adversos , Fenômenos Fisiológicos da Nutrição Materna , Fenilefrina/farmacologia , PPAR gama/metabolismo , PPAR gama/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio/metabolismo , Artéria Renal/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Vasoconstrição/efeitos dos fármacos
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