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1.
Iran J Public Health ; 53(2): 376-386, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38894847

RESUMEN

Background: We aimed to distinguish the different Chinese medicine (CM) syndromes of acquired immune deficiency syndrome (AIDS) patients at the proteomics level. Methods: We collected AIDS patients diagnosed with different CM syndromes from Weishi County, Kaifeng City, Henan Province, China, including Qi-deficiency syndrome (named QD group) and dampness-heat syndrome (named DH group). Healthy people were collected as controls from Weishi County, Kaifeng city, Henan Province, China. The plasma from three groups were labeled with ITRAQ, LC/MC was used for protein quantitative analysis. Finally, sequence search and cluster analysis were performed. Results: Overall, 27 different proteins were found. Three proteins were up-regulated and 2 proteins down-regulated in the QD group, 11 proteins up-regulated and 13 proteins down-regulated in the DH group. Compared with DH group, there were 7 different proteins in QD group, among which 5 proteins were down-regulated and 2 proteins were up-regulated. When the target protein of DH group was up-regulated, the protein of HC group was down-regulated correspondingly. Conclusion: The significance analysis and clustering of protein results showed that DH group was significantly different from QD group and HC group at the protein level (P<0.05). However, the QD group could not be effectively distinguished from the HC group. AAT, PF4, C-reactive protein and c4bp may be used as potential biomarkers in DH group. Mass spectrometry based on feature selection can be used to classify different CM syndromes.

2.
Clin Interv Aging ; 19: 681-693, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38706635

RESUMEN

Aging and aging-related diseases present a global public health problem. Therefore, the development of efficient anti-aging drugs has become an important area of research. Traditional Chinese medicine is an important complementary and alternative branch of aging-related diseases therapy. Recently, a growing number of studies have revealed that traditional Chinese medicine has a certain delaying effect on the progression of aging and aging-related diseases. Here, we review the progress in research into using traditional Chinese medicine for aging and aging-related diseases (including neurodegenerative diseases, cardiovascular diseases, diabetes, and cancer). Furthermore, we summarize the potential mechanisms of action of traditional Chinese medicine and provide references for further studies on aging and aging-related diseases.


Asunto(s)
Envejecimiento , Medicamentos Herbarios Chinos , Medicina Tradicional China , Neoplasias , Enfermedades Neurodegenerativas , Humanos , Envejecimiento/efectos de los fármacos , Medicina Tradicional China/métodos , Enfermedades Neurodegenerativas/tratamiento farmacológico , Neoplasias/tratamiento farmacológico , Medicamentos Herbarios Chinos/uso terapéutico , Medicamentos Herbarios Chinos/farmacología , Enfermedades Cardiovasculares/tratamiento farmacológico , Enfermedades Cardiovasculares/prevención & control , Diabetes Mellitus/tratamiento farmacológico
3.
Front Microbiol ; 15: 1346955, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38435694

RESUMEN

Diarrheal acquired immune deficiency syndrome (AIDS) seriously affects the quality of life of patients. In this study, we analyzed the differences in the intestinal microbiota among healthy individuals, AIDS patients without diarrhea and AIDS patients with diarrhea through high-throughput sequencing. The microbial diversity in the intestines of patients in the AIDS diarrhea group was significantly increased, and after treatment with Xielikang, the intestinal microbial diversity returned to the baseline level. At the phylum level, compared those in to the healthy (ZC) and AIDS non diarrhea (FN) groups, the relative abundances of Bacteroidetes and Verrucomirobia in the AIDS diarrhea (FA) group before treatment were significantly increased, while the relative abundance of Firmicutes was significantly decreased. Similarly, compared with those in the FA group, the relative abundances of Bacteroidea and Firmicutes in the AIDS diarrhea (FB) group after treatment were significantly increased, while the relative abundance of Firmicutes was significantly decreased after treatment. Additionally, there was no significant difference between the ZC and FN groups. At the genus level, compared with those in the ZC group, the relative abundance of Prevotella and Escherichia_Shigella in the FA group was significantly increased, while the relative abundances of Megamonas and Bifidobacterium was significantly decreased compared to that in the ZC group. After treatment with Xielikang, the relative abundance of Prevotella and Escherichia_Shigella in the FB group were significantly decreased, while the relative abundances of Megamonas and Bifidobacteria were significantly increased than those in the FA group; moreover, there was no significant difference between the ZC and FN groups. The functional prediction results showed that the ketodeoxyoctonate (Kdo) transfer to lipid IVA III and the superpathway of N-acetylglucosamine pathways in the AIDS diarrhea group were significantly altered. The correlation analysis results showed that Dorea was positively correlated with inflammatory factors, while Streptococcus and Lactobacillus were negatively correlated with inflammatory factors. The composition and function of the intestinal microbiota changed significantly in AIDS diarrhea patients, which affected the immune function of the host. The Xielikang capsule modulated the composition of the intestinal microbiota in AIDS diarrhea patients and thus improved immune function and reduced diarrheal symptoms.

4.
Curr HIV Res ; 2024 Jan 19.
Artículo en Inglés | MEDLINE | ID: mdl-38310467

RESUMEN

BACKGROUND: Second-line antiretroviral therapy (ART) was introduced in Henan Province in 2009. The number of people living with human immunodeficiency virus (HIV) starting this therapy is increasing. OBJECTIVE: This study aimed to investigate the survival and factors affecting mortality among this group. METHODS: We conducted a retrospective cohort study of people living with HIV (PLHIV) who switched to second-line ART between May 1, 2010, and May 1, 2016., using the Kaplan-Meier method and Cox proportional hazards models. RESULTS: We followed 3,331 PLHIV for 26,988 person-years, of whom 508 (15.3%) died. The mortality rate was 1.88/100 person-years. After adjusting for confounding factors, we found being a woman (hazard ratio [HR], 0.66; 95% confidence interval [CI] 0.55-0.79), > 50 years old (HR, 2.69; 95%CI, 2.03-3.56), single/windowed (HR, 1.26; 95%CI, 1.04-1.52), having > 6 years of education (HR, 0.78; 95%CI, 0.65-0.94), Chinese medicine (HR, 0.75; 95%CI, 0.52-0.96), liver injury (HR, 1.58; 95%CI, 1.19-2.10), and CD4+ T cell count <200 cells/µl (HR, 1.94; 95%CI, 1.47-2.55), or 200-350 cells/µl (HR, 1.37; 95%CI, 1.03-1.82) were associated with mortality risk. CONCLUSIONS: We found lower mortality among PLHIV who switched to second-line ART than most previous studies. The limitations of a retrospective cohort may, therefore, have biased the data, and prospective studies are needed to confirm the results. Moreover, Chinese medicine combined with second-line ART shows potential as a treatment for HIV.

5.
AIDS Res Ther ; 21(1): 10, 2024 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-38350942

RESUMEN

Acquired Immune Deficiency Syndrome (AIDS) is a highly dangerous infectious disease caused by the Human Immunodeficiency Virus (HIV), a virus that attacks the human immune system. To explore the correlation between intestinal fungal community and immune function (Immune cells and inflammatory factors) in people living with HIV/AIDS (PLWHA). The feces and blood samples were collected from two groups of subjects: PLWHA and healthy controls. High-throughput sequencing of the internal transcribed spacer 1, flow cytometry, and ELISA were performed to analyze the differences and correlations between fungal microbiota, cellular immune status and serum inflammatory factors in the two groups. There were significant differences in the composition of fungal microbiota between the two groups. The relative abundance of Candida, Bjerkandera, and Xeromyces in PLWHA was significantly higher than that of healthy volunteers (P < 0.01), while the relative abundance of Mycospaerella, Xeroxysium, Penicillium, and Glomerella in PLWHA was significantly lower than that of healthy volunteers. The correlation analysis results show that Mycospaerella and Xeromyces are significantly positively correlated with CD4+/CD8+ T cells and the anti-inflammatory cytokine IL-4. On the other hand, Candida was positively correlated with pro-inflammatory factors negatively correlated with CD4+/CD8+ T cells and the anti-inflammatory cytokine IL-4, while it is positively correlated with pro-inflammatory cytokines. The significant increase in the relative abundance of Candida may be one of the important causes of intestinal damage in PLWHA. The results of this study contribute to the understanding of the relationship between fungal microbiota structure and immune function in the gut ecology of PLWHA.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Infecciones por VIH , Micobioma , Humanos , Linfocitos T CD8-positivos , Interleucina-4 , Citocinas , Antiinflamatorios
6.
BMC Infect Dis ; 23(1): 584, 2023 Sep 06.
Artículo en Inglés | MEDLINE | ID: mdl-37674103

RESUMEN

OBJECTIVE: To estimate the prevalence and risk factors associated with tuberculosis (TB) among people living with human immunodeficiency virus (HIV) infection/acquired immunodeficiency syndrome (AIDS) in China. METHODS: A systematic review and meta-analysis were conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines. After the literature was screened based on the inclusion and exclusion criteria, STATA® version 17.0 software was used for the meta-analysis. The heterogeneity among study data was assessed using I2 statistics. Subgroup analysis and meta-regressions were performed to further explore the source of heterogeneity. RESULTS: A total of 5241 studies were retrieved. Of these, 44 studies were found to be eligible. The pooled prevalence of HIV/TB co-infection was 6.0%. The risk factors for HIV/TB co-infection included a low CD4+ T cell count, smoking, intravenous drug use and several other sociodemographic and clinical factors. Bacillus Calmette-Guérin (BCG) vaccination history was a protective factor. CONCLUSION: A high prevalence of TB was observed among people living with HIV/AIDS in China. Low CD4+ T cell count, smoking, and intravenous drug use were the primary risk factors for HIV/TB co-infection, whereas BCG vaccination history was a protective factor. Checking for TB should be prioritized in HIV screening and healthcare access. SYSTEMATIC REVIEW REGISTRATION: Registered on PROSPERO, Identifier: CRD42022297754.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Coinfección , Tuberculosis , Humanos , Vacuna BCG , Coinfección/epidemiología , Prevalencia , Factores de Riesgo , Tuberculosis/epidemiología , China/epidemiología
7.
Am J Chin Med ; 51(5): 1189-1209, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-37314412

RESUMEN

HIV mutations occur frequently despite the substantial success of combination antiretroviral therapy, which significantly impairs HIV progression. Failure to develop specific vaccines, the occurrence of drug-resistant strains, and the high incidence of adverse effects due to combination antiviral therapy regimens call for novel and safer antivirals. Natural products are an important source of new anti-infective agents. For instance, curcumin inhibits HIV and inflammation in cell culture assays. Curcumin, the principal constituent of the dried rhizomes of Curcuma longa L. (turmeric), is known as a strong anti-oxidant and anti-inflammatory agent with different pharmacological effects. This work aims to assess curcumin's inhibitory effects on HIV in vitro and to explore the underpinning mechanism, focusing on CCR5 and the transcription factor forkhead box protein P3 (FOXP3). First, curcumin and the RT inhibitor zidovudine (AZT) were evaluated for their inhibitory properties. HIV-1 pseudovirus infectivity was determined by green fluorescence and luciferase activity measurements in HEK293T cells. AZT was used as a positive control that inhibited HIV-1 pseudoviruses dose-dependently, with IC50 values in the nanomolar range. Then, a molecular docking analysis was carried out to assess the binding affinities of curcumin for CCR5 and HIV-1 RNase H/RT. The anti-HIV activity assay showed that curcumin inhibited HIV-1 infection, and the molecular docking analysis revealed equilibrium dissociation constants of [Formula: see text]9.8[Formula: see text]kcal/mol and [Formula: see text]9.3[Formula: see text]kcal/mol between curcumin and CCR5 and HIV-1 RNase H/RT, respectively. To examine curcumin's anti-HIV effect and its mechanism in vitro, cell cytotoxicity, transcriptome sequencing, and CCR5 and FOXP3 amounts were assessed at different concentrations of curcumin. In addition, human CCR5 promoter deletion constructs and the FOXP3 expression plasmid pRP-FOXP3 (with an EGFP tag) were generated. Whether FOXP3 DNA binding to the CCR5 promoter was blunted by curcumin was examined using transfection assays employing truncated CCR5 gene promoter constructs, a luciferase reporter assay, and a chromatin immunoprecipitation (ChIP) assay. Furthermore, micromolar concentrations of curcumin inactivated the nuclear transcription factor FOXP3, which resulted in decreased expression of CCR5 in Jurkat cells. Moreover, curcumin inhibited PI3K-AKT activation and its downstream target FOXP3. These findings provide mechanistic evidence encouraging further assessment of curcumin as a dietary agent used to reduce the virulence of CCR5-tropic HIV-1. Curcumin-mediated FOXP3 degradation was also reflected in its functions, namely, CCR5 promoter transactivation and HIV-1 virion production. Furthermore, curcumin inhibition of CCR5 and HIV-1 might constitute a potential therapeutic strategy for reducing HIV progression.


Asunto(s)
Curcumina , Infecciones por VIH , VIH-1 , Humanos , Curcumina/farmacología , Curcumina/química , Curcuma/química , VIH-1/genética , VIH-1/metabolismo , Células HEK293 , Simulación del Acoplamiento Molecular , Fosfatidilinositol 3-Quinasas , Quimiocinas , Infecciones por VIH/tratamiento farmacológico , Infecciones por VIH/genética , Luciferasas , Ribonucleasa H/farmacología , Factores de Transcripción Forkhead/farmacología , Receptores CCR5/genética , Receptores CCR5/metabolismo
8.
Int J Mol Sci ; 24(4)2023 Feb 14.
Artículo en Inglés | MEDLINE | ID: mdl-36835230

RESUMEN

Accumulated evidence shows that elevated urotensin II (UII) levels are associated with cardiovascular diseases. However, the role of UII in the initiation, progression, and regression of atherosclerosis remains to be verified. Different stages of atherosclerosis were induced in rabbits by a 0.3% high cholesterol diet (HCD) feeding, and either UII (5.4 µg/kg/h) or saline was chronically infused via osmotic mini-pumps. UII promoted atherosclerotic fatty streak formation in ovariectomized female rabbits (34% increase in gross lesion and 93% increase in microscopic lesion), and in male rabbits (39% increase in gross lesion). UII infusion significantly increased the plaque size of the carotid and subclavian arteries (69% increase over the control). In addition, UII infusion significantly enhanced the development of coronary lesions by increasing plaque size and lumen stenosis. Histopathological analysis revealed that aortic lesions in the UII group were characterized by increasing lesional macrophages, lipid deposition, and intra-plaque neovessel formation. UII infusion also significantly delayed the regression of atherosclerosis in rabbits by increasing the intra-plaque macrophage ratio. Furthermore, UII treatment led to a significant increase in NOX2 and HIF-1α/VEGF-A expression accompanied by increased reactive oxygen species levels in cultured macrophages. Tubule formation assays showed that UII exerted a pro-angiogenic effect in cultured endothelial cell lines and this effect was partly inhibited by urantide, a UII receptor antagonist. These findings suggest that UII can accelerate aortic and coronary plaque formation and enhance aortic plaque vulnerability, but delay the regression of atherosclerosis. The role of UII on angiogenesis in the lesion may be involved in complex plaque development.


Asunto(s)
Aterosclerosis , Hipercolesterolemia , Placa Aterosclerótica , Urotensinas , Animales , Conejos , Masculino , Femenino , Placa Aterosclerótica/metabolismo , Aterosclerosis/metabolismo , Urotensinas/metabolismo , Urotensinas/farmacología , Macrófagos/metabolismo , Aorta/metabolismo , Hipercolesterolemia/metabolismo
9.
Infect Drug Resist ; 15: 7037-7042, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36483146

RESUMEN

Background: Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has spread rapidly to become a global pandemic. Opportunistic infections (OIs) are common in patients with acquired immunodeficiency syndrome (AIDS). Mycobacterium avium complex (MAC) and oral candidiasis (OC) are frequently responsible for such infections. Here, we describe a patient with a recent history of COVID-19 who was also diagnosed with human immunodeficiency virus (HIV), MAC, and OC. Case Presentation: The patient was a 23-year-old woman with a past medical history of HIV infection who was diagnosed with SARS-CoV-2 infection 6 days prior to her referral to hospital. Her chief complaints were chest distress and continuous fever with a background of a 5-month history of anemia and tuberculosis (TB). Chest X-ray showed bilateral parenchymal infiltrates suspicious for COVID-19. She was treated with oxygen, empiric antibacterial and antiretroviral therapy. Further workup showed MAC and OC infection. She was started on ethambutol, rifampin and antifungal treatment for influenzas and her symptoms resolved in 8 weeks. Follow-up chest computed tomography scanning showed that the lung lesions disappeared within a short period of time. Conclusion: A thorough history and clinical examination are vital to arriving at the correct diagnosis or diagnoses. With the COVID-19 pandemic, clinicians caring for immunosuppressed patients need to remain vigilant of the simultaneous presence of OIs. This report highlights the importance of the treatment and prevention of OIs in HIV-infected persons, which may reduce adverse consequences after infection with SARS-CoV-2.

10.
Int J Gen Med ; 15: 8353-8363, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36465269

RESUMEN

Coronavirus disease 2019 (COVID-19) remains an uncontained, worldwide pandemic. While battling the disease in China, the Chinese government has actively promoted the use of traditional Chinese medicine, and many studies have been conducted to determine the efficacy of traditional Chinese medicine for treating COVID-19. The present review discusses the effectiveness and safety of traditional Chinese medicine in curing COVID-19 and provides clinical evidence from all confirmed cases in China. Applications of traditional Chinese medicine and specific recipes for treating other viral infections, such as those caused by severe acute respiratory syndrome coronavirus and influenza A viruses (including H1N1), are also discussed. Studies have reported that traditional Chinese medicine treatment plays a significant role in improving clinical symptoms. Therefore, further investigation may be of high translational value in revealing novel targeted therapies for COVID-19.

11.
Medicine (Baltimore) ; 101(38): e30833, 2022 Sep 23.
Artículo en Inglés | MEDLINE | ID: mdl-36197192

RESUMEN

BACKGROUND: Actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) is associated with prognosis in many cancers. The aim of this study was to systematically evaluate the potential correlation between AFAP1-AS1 and the prognosis of digestive system cancers (DSC). METHODS: EMBASE, Web of Science, Cochrane Library, PubMed, Wanfang Data (Chinese), and CNKI (Chinese) were comprehensively searched for literature published from the establishment of the database to September 2021.All case-control studies that met the inclusion criteria were retrieved; additionally manual retrieval and literature tracing was performed. After extracting the relevant data, Revman 5.3.5 software was used for meta-analysis. RESULTS: Eighteen studies were included in analyses, high expression of AFAP1-AS1 was significantly correlated with poor prognosis in DSC, including overall survival (HR = 1.93, 95% CI: 1.72-2.17, P < .001) and disease-free survival/progression-free survival (HR = 1.87, 95% CI: 1.56-2.26, P < .001). In addition, the expression of AFAP1-AS1 was significantly correlated with tumor size, tumor stage, and lymph node metastasis. CONCLUSION: High expression of AFAP1-AS1 was associated with poor prognosis in DSC. Therefore, it could be used as a potential marker for evaluating prognosis in DSC.


Asunto(s)
Neoplasias del Sistema Digestivo , ARN Largo no Codificante , Línea Celular Tumoral , Proliferación Celular , Neoplasias del Sistema Digestivo/genética , Regulación Neoplásica de la Expresión Génica , Humanos , Pronóstico , ARN sin Sentido , ARN Largo no Codificante/genética
12.
Trials ; 23(1): 665, 2022 Aug 17.
Artículo en Inglés | MEDLINE | ID: mdl-35978377

RESUMEN

BACKGROUND: Acquired immune deficiency syndrome is caused by humans and is high worldwide. Active antiretroviral therapy emerged in the late 1990s and is effective against AIDS. However, despite the extensive research on AIDS, there is still no vaccine or cure. The benefits of traditional Chinese medicine (TCM) for AIDS are increasingly recognised, especially by patients with asymptomatic HIV infection. METHODS/DESIGN: The proposed trial will enrol 216 eligible patients who will be randomised into treatment and control groups. After 72 weeks of intervention, the efficacy and safety of TCM for patients with AIDS will be assessed. The variables that will be measured include clinical symptoms, TCM syndromes, viral load, immunological indicators, inflammatory factors, quality of life, patient-reported outcomes and safety assessment. DISCUSSION: The study aim to compare the effectiveness and safety of TCM for asymptomatic AIDS and explore its potential underlying mechanism. Additionally, the findings will provide a reference for the use of TCM to delay the onset and control the progression of HIV/AIDS. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR1800018365. Registered on 13 September 2018.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Medicamentos Herbarios Chinos , Infecciones por VIH , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Medicamentos Herbarios Chinos/efectos adversos , Infecciones por VIH/diagnóstico , Infecciones por VIH/tratamiento farmacológico , Humanos , Medicina Tradicional China/métodos , Morbilidad , Estudios Multicéntricos como Asunto , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Resultado del Tratamiento
13.
Drug Des Devel Ther ; 16: 2731-2753, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-36003311

RESUMEN

Purpose: This study was the first to screen the active compounds of Jian Aikang Concentrated Pill (JAKCP) with network pharmacology, predict its potential targets, screen the signaling pathways, and combine with cellular experimental validation to explore the potential mechanism of JAKCP for the treatment of acquired immunodeficiency syndrome (AIDS). Methods: The main compounds and targets of Chinese herbs in JAKCP were identified by TCMSP; the targets of AIDS were collected from Genecards, Online Mendelian Inheritance in Man (OMIM), Disgenet, Therapeutic Target Database (TTD) and Drugbank; the network of "Chinese herbs-active compounds-targets" for JAKCP was constructed by Cytoscape, and protein-protein interaction (PPI) network was constructed using STRING to generate the intersection targets, Metascape was conducted to analyze the Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG), and the network of "main active compounds-core targets-pathways" was constructed by Cytoscape. Finally, the effect of JAKCP on the survival rate of HIV pseudovirus-infected MT-4 cells was investigated by CCK-8 assay, and the predicted targets were verified by ELISA, qPCR and Western blot. Results: A total of 147 active compounds of JAKCP were screened covering 351 targets and 416 AIDS disease targets were obtained, besides 140 intersection targets and 321 KEGG pathways were collected. Ultimately, quercetin, kaempferol, stigmasterol, beta-sitosterol, epigallocatechin gallate were identified as the important compounds, the core targets are HSP90AA1, IL-10, IL-6, TNF, IL-1ß, TP53, and IL-1ɑ, and the biological pathways and processes mainly include T cell activation, regulation of DNA-binding transcription factor activity and apoptotic signaling pathway. Experiments on the targets of "T cell activation" demonstrated that JAKCP promotes the survival of HIV pseudovirus-infected MT-4 cells. Also, JAKCP down-regulated mRNA and protein levels of IL-1ɑ, IL-1ß, and IL-6 while up-regulated mRNA and protein levels of IL-2, IL-6ST, and IL-10 in vitro. Conclusion: JAKCP exerted regulatory immune functions through multi-component, multi-target and multi-pathway, thereby providing novel ideas and clues for the treatment of AIDS.


Asunto(s)
Síndrome de Inmunodeficiencia Adquirida , Medicamentos Herbarios Chinos , Farmacología en Red , Síndrome de Inmunodeficiencia Adquirida/tratamiento farmacológico , Medicamentos Herbarios Chinos/farmacología , Medicamentos Herbarios Chinos/uso terapéutico , Humanos , Inmunidad , Interleucina-10 , Interleucina-6 , Simulación del Acoplamiento Molecular , Farmacología en Red/métodos , ARN Mensajero
14.
Aging (Albany NY) ; 14(13): 5590-5610, 2022 07 08.
Artículo en Inglés | MEDLINE | ID: mdl-35802774

RESUMEN

Protein tyrosine phosphatase, non-receptor type 11 (PTPN11) is a multifunctional tyrosine phosphatase and has a significant part in many types of tumors. As of yet, neither the expression profile of PTPN11 nor its significance in pan-cancer diagnosis has been clarified. With the assistance of The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO), we have comprehensively mapped the expression profiles, prognostic significance, genetic alteration, phosphorylation status, infiltration of immune cells, and functional properties of PTPN11 in 33 human tumors. There was an inconsistent expression of PTPN11 in different tumors, and the alteration of PTPN11 expression predicted the survival outcomes of cancer patients. A significant association was found between the genetic alteration levels of PTPN11 and some tumor predictions. Besides, the reduced PTPN11 phosphorylation levels were observed in breast cancer, clear cell RCC, head and neck carcinoma, and lung adenocarcinoma (LUAD). Furthermore, there was a significant association between PTPN11 expression and infiltration of cancer-associated fibroblasts and endothelial cells, along with tumor mutation burden, microsatellite instability, mismatch repair genes, and immunoregulators. Finally, pathway enrichment analysis demonstrated that PTPN11-associated terms and pathways were involved in malignancy. Taken together, PTPN11 may become a new biomarker and target for cancer therapy.


Asunto(s)
Neoplasias de Cabeza y Cuello , Neoplasias Pulmonares , Biomarcadores de Tumor/genética , Células Endoteliales/metabolismo , Humanos , Neoplasias Pulmonares/genética , Pronóstico , Proteína Tirosina Fosfatasa no Receptora Tipo 11/genética , Proteína Tirosina Fosfatasa no Receptora Tipo 11/metabolismo
15.
Circ Res ; 130(11): 1647-1659, 2022 05 27.
Artículo en Inglés | MEDLINE | ID: mdl-35443807

RESUMEN

BACKGROUND: Endothelial-to-mesenchymal transition (EndMT) has been identified as a critical driver of vascular inflammation and atherosclerosis, and TGF-ß (transforming growth factor ß) is a key mediator of EndMT. Both EndMT and atherosclerosis are promoted by disturbed flow, whereas unidirectional laminar flow limits EndMT and is atheroprotective. How EndMT and endothelial TGF-ß signaling are regulated by different flow patterns is, however, still poorly understood. METHODS: Flow chamber experiments in vitro and endothelium-specific knockout mice were used to study the role of tenascin-X in the regulation of EndMT and atherosclerosis as well as the underlying mechanisms. RESULTS: In human endothelial cells as well as in human and mouse aortae, unidirectional laminar flow but not disturbed flow strongly increased endothelial expression of the extracellular matrix protein TN-X (tenascin-X) in a KLF4 (Krüppel-like factor 4) dependent manner. Mice with endothelium-specific loss of TN-X (EC-Tnxb-KO) showed increased endothelial TGF-ß signaling as well as increased endothelial expression of EndMT and inflammatory marker genes. When EC-Tnxb-KO mice were subjected to partial carotid artery ligation, we observed increased vascular remodeling. EC-Tnxb-KO mice crossed to low-density lipoprotein receptor-deficient mice showed advanced atherosclerotic lesions after being fed a high-fat diet. Treatment of EC-Tnxb-KO mice with an anti-TGF-beta antibody or additional endothelial loss of TGF-beta receptors 1 and 2 normalized endothelial TGF-beta signaling and prevented EndMT. In in vitro studies, we found that TN-X through its fibrinogen-like domain directly interacts with TGF-ß and thereby interferes with its binding to the TGF-ß receptor. CONCLUSIONS: In summary, we show that TN-X is a central mediator of flow-induced inhibition of EndMT, endothelial inflammation and atherogenesis, which functions by binding to and by blocking the activity of TGF-ß. Our data identify a novel mechanism of flow-dependent regulation of vascular TGF-ß, which holds promise for generating new strategies to prevent vascular inflammation and atherosclerosis.


Asunto(s)
Aterosclerosis , Células Endoteliales , Animales , Aterosclerosis/genética , Aterosclerosis/metabolismo , Aterosclerosis/prevención & control , Células Cultivadas , Células Endoteliales/metabolismo , Endotelio/metabolismo , Transición Epitelial-Mesenquimal/fisiología , Inflamación/metabolismo , Ratones , Transducción de Señal , Tenascina , Factor de Crecimiento Transformador beta/metabolismo
17.
Environ Technol ; 42(19): 3048-3054, 2021 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-31969084

RESUMEN

Simultaneous nitrification and denitrification (SND) were coupled with a denitrifying phosphorus removal (DPR) to achieve simultaneous nutrient and carbon removal. With influent chemical oxygen demand (COD), ammonia-N (NH4+-N), and total phosphorus (TP) concentrations of 250, 50, and 8 mg/L, the SND-DPR coupled system achieved stable nutrient removal efficiency of COD, NH4+-N, TN and TP were 91.8 ± 1.7%, 88.4 ± 1.8%, 64 ± 3.3% and 99.2 ± 0.6%, respectively. Enhancing the C/N ratio strengthened the storage of intracellular polymers and provided sufficient intracellular carbon sources for phosphorus uptake. The nutrient removal efficiency reached the highest level at a C/N ratio of 5, and no advantage was observed after increasing the C/N ratio to 7. Nutrients were mainly removed during the aerobic stage at a low DO concentration as well during the anoxic stage, which helped achieve concurrent nitrification and denitrification by ordinary heterotrophic organisms (OHOs), promote denitrifying and aerobic phosphorus removal, and conserve organic carbon demand and energy consumption for aeration. The system was limited for DO in the aerobic stage at a low DO concentration, resulting in a deficiency in electron acceptors (O2 and NO3-N) and limiting the subsequent promotion of phosphorus uptake and TN removal. The limited DO content in the low DO stage was the key factor involved in enhancing the nutrient removal efficiency along with the increasing influent C/N ratio.


Asunto(s)
Nitrificación , Fósforo , Reactores Biológicos , Carbono , Desnitrificación , Nitrógeno , Aguas del Alcantarillado , Eliminación de Residuos Líquidos , Aguas Residuales
18.
Acta Pharmacol Sin ; 41(4): 546-553, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31685976

RESUMEN

Increasing levels of plasma urotensin II (UII) are positively associated with atherosclerosis. In this study we investigated the role of macrophage-secreted UII in atherosclerosis progression, and evaluated the therapeutic value of urantide, a potent competitive UII receptor antagonist, in atherosclerosis treatment. Macrophage-specific human UII-transgenic rabbits and their nontransgenic littermates were fed a high cholesterol diet for 16 weeks to induce atherosclerosis. Immunohistochemical staining of the cellular components (macrophages and smooth muscle cells) of aortic atherosclerotic lesions revealed a significant increase (52%) in the macrophage-positive area in only male transgenic rabbits compared with that in the nontransgenic littermates. However, both male and female transgenic rabbits showed a significant decrease (45% in males and 31% in females) in the smooth muscle cell-positive area compared with that of their control littermates. The effects of macrophage-secreted UII on the plaque cellular components were independent of plasma lipid level. Meanwhile the wild-type rabbits were continuously subcutaneously infused with urantide (5.4 µg· kg-1· h-1) using osmotic mini-pumps. Infusion of urantide exerted effects opposite to those caused by UII, as it significantly decreased the macrophage-positive area in male wild-type rabbits compared with that of control rabbits. In cultured human umbilical vein endothelial cells, treatment with UII dose-dependently increased the expression of the adhesion molecules VCAM-1 and ICAM-1, and this effect was partially reversed by urantide. The current study provides direct evidence that macrophage-secreted UII plays a key role in atherogenesis. Targeting UII with urantide may promote plaque stability by decreasing macrophage-derived foam cell formation, which is an indicator of unstable plaque.


Asunto(s)
Aterosclerosis/tratamiento farmacológico , Células Endoteliales de la Vena Umbilical Humana/efectos de los fármacos , Macrófagos/efectos de los fármacos , Fragmentos de Péptidos/farmacología , Placa Aterosclerótica/tratamiento farmacológico , Urotensinas/farmacología , Animales , Aterosclerosis/metabolismo , Aterosclerosis/patología , Células Cultivadas , Dieta Alta en Grasa/efectos adversos , Relación Dosis-Respuesta a Droga , Femenino , Células Endoteliales de la Vena Umbilical Humana/metabolismo , Humanos , Infusiones Subcutáneas , Macrófagos/metabolismo , Masculino , Fragmentos de Péptidos/administración & dosificación , Fragmentos de Péptidos/sangre , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patología , Conejos , Urotensinas/administración & dosificación , Urotensinas/sangre
19.
Molecules ; 24(4)2019 Feb 13.
Artículo en Inglés | MEDLINE | ID: mdl-30781735

RESUMEN

Progastrin-releasing peptide (ProGRP), which is known to be highly specific and sensitive to small cell lung cancer (SCLC), has been proven to be a valuable substitute for neuron-specific enolase in SCLC diagnostics and monitoring, especially in its early stages. The detection of ProGRP levels also facilitates a selection of therapeutic treatments. For the fabrication of our proposed biosensor, titanium (IV) oxide microparticles were first used, followed by dispersing gold nanoparticles into chitosan and immobilizing them onto a carbon paste electrode (CPE) surface. The developed immunosensor exhibits a much higher biosensing performance in comparison with current methods, when it comes to the detection of ProGRP. Therefore, the proposed CPE/TiO2/(CS+AuNPs)/anti-ProGRP/BSA/ProGRP is excellent for the development of a compact diagnostics apparatus.


Asunto(s)
Biomarcadores de Tumor/sangre , Técnicas Biosensibles , Fragmentos de Péptidos/sangre , Carcinoma Pulmonar de Células Pequeñas/sangre , Oro/química , Humanos , Nanocompuestos/química , Fosfopiruvato Hidratasa/genética , Proteínas Recombinantes/sangre , Carcinoma Pulmonar de Células Pequeñas/genética , Carcinoma Pulmonar de Células Pequeñas/patología , Titanio/química
20.
J Tradit Chin Med ; 39(1): 111-117, 2019 02.
Artículo en Inglés | MEDLINE | ID: mdl-32186031

RESUMEN

OBJECTIVE: To estimate the prevalence trend and risk factors for anemia in patients with human immunodeficiency virus (HIV) infection receiving antiretroviral therapy (ART) in rural China. METHODS: We conducted cross-sectional studies among the same population in 2010, 2012, and 2014, based on data from standard medical record registers. Factors associated with anemia were evaluated using a logistic regression model. RESULTS: The number of patients with HIV infection included in each cross-sectional study was 1456 in 2010, 1531 in 2012, and 1567 in 2014, and the prevalence of anemia was 44.3%, 34.7%, and 27.6%, respectively. The prevalence of anemia was lower in female patients in 2010 [odds ratio (OR) 0.68; 95% confidence interval (CI) 0.55-0.85]; however, there was no difference by sex in 2012 (OR 0.90; 95% CI 0.72-1.11) and 2014 (OR 1.05; 95% CI 0.84-1.32). Patients with a higher level of education had a lower risk of anemia in 2014 (OR 0.72; 95% CI 0.56-0.92), but there was no difference in 2010 (OR 1.00; 95% CI 0.79-1.25) and 2012 (OR 0.99; 95% CI 0.79-1.24). Patients who had received a longer duration of ART had a higher risk of anemia in 2014 (OR 1.74; 95% CI 1.15-2.64), but there was no difference in 2010 and 2012 (P > 0.05). Patients receiving Traditional Chinese Medicine (TCM) therapy had a lower risk of anemia. CONCLUSION: The prevalence of anemia among patients with HIV infection receiving ART decreased between 2010 and 2014 in Henan Province but was still higher than the prevalence in the general population of China. TCM therapy can potentially decrease the risk of anemia among patients with HIV infection.


Asunto(s)
Anemia/epidemiología , Anemia/etiología , Fármacos Anti-VIH/uso terapéutico , Infecciones por VIH/complicaciones , Infecciones por VIH/tratamiento farmacológico , Adulto , China , Intervalos de Confianza , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Prevalencia , Factores de Riesgo
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