Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 108
Filtrar
1.
Chem Biodivers ; 21(2): e202301712, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38031386

RESUMO

A novel staurosporine derivate, streptomholyrine A (1), along with 6 known compounds were identified from the rice-based solid fermentation of marine-derived Streptomyces sp. ZS-A121. The planar structure and absolute configuration of streptomholyrine A were elucidated using a combination of 1D, 2D NMR, HRESIMS data analysis, chemical transformation, ECD and NMR calculations. Screening of all these compounds revealed their cytotoxic activity against HCT-116 cell lines, with IC50 values ranging from 0.012 to 11.67 µM, except for the known 1H-indole-3-hydroxyacetyl, which showed no inhibition activity. Furthermore, streptomholyrine A, along with two known staurosporine derivatives, k252d and staurosporine, exhibited activities against Candida albicans, with MICs of 12.5, 25.0 and 50.0 µg/ml, respectively.


Assuntos
Actinobacteria , Antineoplásicos , Streptomyces , Humanos , Estaurosporina/farmacologia , Estaurosporina/metabolismo , Antifúngicos/farmacologia , Antifúngicos/metabolismo , Streptomyces/química , Antineoplásicos/química , Estrutura Molecular
2.
J Transl Med ; 21(1): 869, 2023 11 30.
Artigo em Inglês | MEDLINE | ID: mdl-38037074

RESUMO

BACKGROUND: Natural killer (NK) cells play an important first-line role against tumour and viral infections and are regulated by inhibitory receptor expression. Among these inhibitory receptors, the expression, function, and mechanism of cluster of differentiation 47 (CD47) on NK cells during human immunodeficiency virus (HIV) infection remain unclear. METHODS: Fresh peripheral blood mononuclear cells (PBMCs) were collected from people living with HIV (PLWH) and HIV negative controls (NC) subjects. Soluble ligand expression levels of CD47 were measured using ELISA. HIV viral proteins or Toll-like receptor 7/8 (TLR7/8) agonist was used to investigate the mechanisms underlying the upregulation of CD47 expression. The effect of CD47 on NK cell activation, proliferation, and function were evaluated by flow cytometry. RNA-seq was used to identify downstream pathways for CD47 and its ligand interactions. A small molecule inhibitor was used to restore the inhibition of NK cell function by CD47 signalling. RESULTS: CD47 expression was highly upregulated on the NK cells from PLWH, which could be due to activation of the Toll-like receptor 7/8 (TLR7/8) pathway. Compared with NC subjects, PLWH subjects exhibited elevated levels of CD47 ligands, thrombospondin-1 (TSP1), and counter ligand signal regulatory protein-α (SIRPα). The TSP1-CD47 axis drives the suppression of interferon gamma (IFN-γ) production and the activation of the Janus kinase signal transducer and activator of transcription (JAK-STAT) pathway in NK cells. After treatment with a STAT3 inhibitor, the NK cells from PLWH showed significantly improved IFN-γ production. CONCLUSIONS: The current data indicate that the binding of the inhibitory receptor CD47 to plasma TSP1 suppresses NK cell IFN-γ production by activating the JAK/STAT3 pathway during HIV infection. Our results suggest that CD47 and its related signalling pathways could be targets for improving NK cell function in people living with HIV.


Assuntos
Infecções por HIV , Receptor 7 Toll-Like , Humanos , Antígeno CD47 , Janus Quinases/metabolismo , Células Matadoras Naturais/metabolismo , Leucócitos Mononucleares/metabolismo , Ligantes , Fator de Transcrição STAT3/metabolismo , Interferon gama/metabolismo
3.
Stem Cell Res Ther ; 14(1): 170, 2023 06 26.
Artigo em Inglês | MEDLINE | ID: mdl-37365654

RESUMO

BACKGROUND: Brainstem stroke causes severe and persistent neurological impairment. Due to the limited spontaneous recovery and regeneration of the disrupted neural circuits, transplantation of exogenous neural stem cells (NSCs) was an alternative, while there were limitations for primitive NSCs. METHODS: We established a mouse model of brainstem stroke by injecting endothelin in the right pons. Brain-derived neurotrophic factor (BDNF)- and distal-less homeobox 2 (Dlx2)-modified NSCs were transplanted to treat brainstem stroke. Transsynaptic viral tracking, immunostaining, magnetic resonance imaging, behavioral testing, and whole-cell patch clamp recordings were applied to probe the pathophysiology and therapeutic prospects of BDNF- and Dlx2-modified NSCs. RESULTS: GABAergic neurons were predominantly lost after the brainstem stroke. No endogenous NSCs were generated in situ or migrated from the neurogenesis niches within the brainstem infarct region. Co-overexpressions of BDNF and Dlx2 not only promoted the survival of NSCs, but also boosted the differentiation of NSCs into GABAergic neurons. Results from transsynaptic virus tracking, immunostaining, and evidence from whole-cell patch clamping revealed the morphological and functional integration of the grafted BDNF- and Dlx2-modified NSCs-derived neurons with the host neural circuits. Neurological function was improved by transplantation of BDNF- and Dlx2-modified NSCs in brainstem stroke. CONCLUSIONS: These findings demonstrated that BDNF- and Dlx2-modified NSCs differentiated into GABAergic neurons, integrated into and reconstituted the host neural networks, and alleviated the ischemic injury. It thus provided a potential therapeutic strategy for brainstem stroke.


Assuntos
Células-Tronco Neurais , Acidente Vascular Cerebral , Camundongos , Animais , Fator Neurotrófico Derivado do Encéfalo/genética , Diferenciação Celular , Modelos Animais de Doenças , Neurônios GABAérgicos/patologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/patologia
4.
Mar Genomics ; 70: 101033, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37355293

RESUMO

Streptomyces sp. HNA39 is a promising candidate for the production of antineoplastic metabolites screened from a collection of 448 actinomycetes derived from coastal sediments. The complete genome sequence of HNA39 comprises a 7,351,753-bp linear chromosome with a GC content of 71.94%. Whole genome analysis reveals the presence of 29 putative biosynthetic gene clusters (BGCs) encoding secondary metabolites. Among them, a type I PKS BGC shows an 82% similarity with the cyclizidine (CLD) BGC identified from Streptomyces NCIB 11649. LC-MS profiles further supported the production of new CLD congeners. Bafilomycins were also found produced in abundance, corresponding to another type I PKS BGC highly homologous to that of bafilomycin B1 from S. lohii. CLDs are indolizidine alkaloids consisting a fused five- and six-membered ring system with an intriguing cyclopropane terminal linked by a trans-dienic chain. The cyclization mechanism of the cylopropyl ring, one of its pharmacophores, is still unknown. Genome sequencing of the new CLD producer and subsequent comparative analysis of their gene clusters would further our understanding of the chemistry behind cyclopropane formation.


Assuntos
Streptomyces , Streptomyces/genética , Sequência de Bases , Mapeamento Cromossômico , China , Família Multigênica
5.
Front Nutr ; 10: 1101182, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36992906

RESUMO

Cistanche is a tonic Chinese medicine commonly used in traditional Chinese medicine, with 2016, CFSA through the alxa desert cistanche safety evaluation, cistanche began to officially enter the food field. At present, the research on cistanche mainly focuses on the extraction, isolation and purification and pharmacological effects, and its pharmacological effects such as neuroprotective effects, immunomodulation, antioxidant anticancer and hepatoprotective liver protection have attracted the attention of researchers. This review mainly reviews the research status, chemical composition and health benefits, analyzes its application prospects in food, and aims to provide certain theoretical support for the safe application of cistanche in functional food.

6.
Front Immunol ; 14: 1106881, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36875092

RESUMO

The complex mechanism of immune-system damage in HIV infection is incompletely understood. HIV-infected "rapid progressors" (RPs) have severe damage to the immune system early in HIV infection, which provides a "magnified" opportunity to study the interaction between HIV and the immune system. In this study, forty-four early HIV-infected patients (documented HIV acquisition within the previous 6 months) were enrolled. By study the plasma of 23 RPs (CD4+ T-cell count < 350 cells/µl within 1 year of infection) and 21 "normal progressors" (NPs; CD4+ T-cell count > 500 cells/µl after 1 year of infection), eleven lipid metabolites were identified that could distinguish most of the RPs from NPs using an unsupervised clustering method. Among them, the long chain fatty acid eicosenoate significantly inhibited the proliferation and secretion of cytokines and induced TIM-3 expression in CD4+ and CD8+ T cells. Eicosenoate also increased levels of reactive oxygen species (ROS) and decreased oxygen consumption rate (OCR) and mitochondrial mass in T cells, indicating impairment in mitochondrial function. In addition, we found that eicosenoate induced p53 expression in T cells, and inhibition of p53 effectively decreased mitochondrial ROS in T cells. More importantly, treatment of T cells with the mitochondrial-targeting antioxidant mito-TEMPO restored eicosenoate-induced T-cell functional impairment. These data suggest that the lipid metabolite eicosenoate inhibits immune T-cell function by increasing mitochondrial ROS by inducing p53 transcription. Our results provide a new mechanism of metabolite regulation of effector T-cell function and provides a potential therapeutic target for restoring T-cell function during HIV infection.


Assuntos
Linfócitos T CD8-Positivos , Infecções por HIV , Humanos , Espécies Reativas de Oxigênio , Proteína Supressora de Tumor p53 , Mitocôndrias , Ácidos Graxos
7.
Front Nutr ; 10: 1117364, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36814512

RESUMO

To study the anti-tumor effect of Cistanche deserticola Y. Ma, HepG2 cells were treated with 0, 3.5, 10.5, 21, 31.5, and 42 µg/ml of total glycosides (TG) from Cistanche deserticola. The HepG2 cell survival rate and 50% inhibition concentration (IC50) were detected using the CCK-8 method, and the level of reactive oxygen species (ROS) was detected by using a DCFH-DA fluorescence probe. Finally, a Seahorse XFe24 energy analyzer (Agilent, United States) was used to detect cell mitochondrial pressure and glycolytic pressure. The results showed that TG could reduce the survival rate of HepG2 cells and that the IC50 level was 35.28 µg/ml. With increasing TG concentration, the level of ROS showed a concentration-dependent upward trend. Energy metabolism showed that each dose group of TG could significantly decline the mitochondrial respiratory and glycolytic functions of HepG2 cells. In conclusion, TG could significantly inhibit the mitochondrial respiration and glycolysis functions of HepG2 cells, increase the level of ROS, and inhibit cell proliferation. Thus, this experiment pointed out that Cistanche deserticola can be used as a source of anti-cancer foods or drugs in the future. However, further studies on its mechanisms and clinical applications are needed.

8.
Cytokine ; 161: 156056, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36240721

RESUMO

BACKGROUND: The mortality rate of patients with sepsis has been increasing in recent years. Alterations of biomarkers levels during treatment are important in evaluating treatment efficacy and predicting outcomes in sepsis. This meta-analysis investigated the relationship between changes in cytokine levels after treatment compared with those on hospital admission, and their relationship with the prognosis of patients with sepsis. METHODS: From conception until August 4, 2021, a complete literature search of the PubMed, Web of Science, and Cochrane Library electronic databases was done. Observational studies where the outcomes of sepsis patients were divided into non-survivors and survivors and which reported cytokine levels at least before treatment in ICU were included in the current study. Standardized mean difference (SMD) with 95% confidence intervals (CI) values from individual studies were pooled using a random-effects model. Quality assessment, subgroup analysis, publication bias, and sensitivity analyses were all carried out. RESULTS: A total of 2570 patients with sepsis from 25 eligible studies were included, and 14 of them measured the cytokine levels before and after treatment in ICU. Among IL-6, TNF-α, IL-1ß and IL-10 levels, those of IL-6 were significantly lower after treatment in ICU than at baseline in patients with sepsis in the survival group (SMD = -0.69, P < 0.0001), but were comparable in the non-survival group (SMD = -0.99, P = 0.0575). Similarly, post-treatment TNF-α levels were significantly lower than those at baseline only in patients with sepsis in the survival group (SMD = -0.44, P < 0.0001), but not in the non-survival group (SMD =-0.17, P = 0.0842). CONCLUSION: This meta-analysis shows that reduced IL-6 and TNF-α levels after sepsis treatment in ICU may be indicators of better prognosis and survival of patients with sepsis.


Assuntos
Citocinas , Sepse , Humanos , Fator de Necrose Tumoral alfa , Interleucina-6 , Sepse/terapia , Biomarcadores
9.
Am J Transl Res ; 14(11): 8117-8128, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36505312

RESUMO

BACKGROUND: MicroRNAs (miRNAs) have been identified to play a role in the development and progression of lung cancer (LC). As of now, the expression and function of miR-370 in LC are still under investigation. Accordingly, this study explores the role and mechanism of miR-370 in LC. METHODS: MiR-370 mimics or inhibitors were used to transfect A549 and NCI-H460 cells to overexpress or inhibit miR-370. The colony formation test and Cell Counting Kit-8 were conducted to detect the cell proliferation activity, and transwell test and wound healing test were conducted to evaluate the cell invasion and migration activities. In addition, the downstream target genes of miR-370 in LC were verified by dual luciferase reporter assay and western blot. RESULTS: Compared to normal tissues and cell lineslines, the miR-370 expression in LC tissues and cells was decreased greatly. Compared to the negative control group, the up-regulation of miR-370 greatly intensified the apoptosis of NCI-H460 cells and weakened the migration, proliferation, and invasion of the cells. However, compared to the inhibitor-negative control group, the downregulation of miR-370 caused the opposite results. Additionally, SMAD family member 1 (SMAD1) was identified as a direct target of miR-370 in LC and could be inhibited by miR-370. Its overexpression restored the impact of miR-370 mimics on LC cells. CONCLUSION: With low expression in LC tissues and cell lineslines, miR-370 is a tumor suppressor that weakens the growth, invasion as well as migration of LC cells by inhibiting SMAD1 expression. Our results may provide novel insights for the biological treatment of LC.

10.
Front Immunol ; 13: 946871, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36268017

RESUMO

The ectonucleotidases CD38 and CD39 have a critical regulatory effect on tumors and viral infections via the adenosine axis. Natural killer (NK) cells produce cytokines, induce cytotoxic responses against viral infection, and acquire immunoregulatory properties. However, the roles of CD38 and CD39 expressed NK cells in HIV disease require elucidation. Our study showed that the proportions of CD38+CD39+ NK cells in HIV-infected individuals were positively associated with HIV viral loads and negatively associated with the CD4+ T cell count. Furthermore, CD38+CD39+ NK cells expressed additional inhibitory receptors, TIM-3 and LAG-3, and produced more TGF-ß. Moreover, autologous NK cells suppressed the proliferation of CD8+ T and CD4+ T cells of HIV-infected individuals, and inhibiting CD38 and CD39 on NK cells restored CD8+ T and CD4+ T cell proliferation in vitro. In conclusion, these data support a critical role for CD38 and CD39 on NK cells in HIV infection and targeting CD38 and CD39 on NK cells may be a potential therapeutic strategy against HIV infection.


Assuntos
Infecções por HIV , Humanos , Receptor Celular 2 do Vírus da Hepatite A , Células Matadoras Naturais , Adenosina , Proliferação de Células , Progressão da Doença , Citocinas , Contagem de Células , Fator de Crescimento Transformador beta
11.
Front Immunol ; 13: 854432, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36110864

RESUMO

Natural killer (NK) cells are crucial for immune responses to viral infections. CD160 is an important NK cell activating receptor, with unknown function in HIV infection. Here, we found that CD160 expression was reduced on NK cells from HIV-infected individuals and its expression was negatively correlated with HIV disease progression. Further, GLUT1 expression and glucose uptake were higher in CD160+ NK cells, and the results of RNA-seq and flow cytometry demonstrated that CD160 positively regulated glucose metabolism through the PI3K/AKT/mTOR/s6k signaling pathway, thereby enhancing NK cell function. Moreover, we determined that reduced CD160 expression on NK cells could be attributed to the higher plasma levels of TGF-ß1 in HIV-infected individuals. Overall, these results highlight the vital role of CD160 in HIV disease progression and regulation of glucose metabolism, indicating a potential target for HIV immunotherapy.


Assuntos
Antígenos CD , Infecções por HIV , Antígenos CD/metabolismo , Progressão da Doença , Proteínas Ligadas por GPI/metabolismo , Glucose/metabolismo , Transportador de Glucose Tipo 1/metabolismo , Humanos , Células Matadoras Naturais , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Receptores Imunológicos/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Fator de Crescimento Transformador beta1/metabolismo
12.
Biomed Res Int ; 2022: 4944758, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35692583

RESUMO

Background: Lung cancer is one of leading causes of human health threatening with approximately 2.09 million initially diagnosed cases and 1.76 million deaths worldwide annually. Pyroptosis is a programmed cell death mediated by Gasdermin family proteins. Pyroptosis could suppress the tumor oncogenesis and progression; nevertheless, pyroptosis could promote tumor growth by forming a suitable microenvironment. Methods: LASSO Cox regression analysis was performed to construct prognostic pyroptosis-related gene (PRG) signature. A ceRNA was constructed to explore the potential lncRNA-miRNA-mRNA regulatory axis in LUSC. Results: The expression of 26 PRGs were increased or decreased in LUSC. We also summarized simple nucleotide variation and copy number variation landscape of PRGs in LUSC. Prognosis analysis suggested a poor overall survival rate in LUSC patients with high expression of IL6, IL1B, ELANE, and CASP6. A pyroptosis-related prognostic signature was developed based on four prognostic PRGs. High-risk score LUSC patients had a poor overall survival rate versus low-risk score patients with an AUC of 0.565, 0.641, and 0.619 in 1-year, 3-year, and 5-year ROC curves, respectively. Moreover, the risk score was correlated with immune infiltration in LUSC. Further analysis revealed that pyroptosis-related prognostic signature was correlated with immune cell infiltration, tumor mutation burden, microsatellite instability, and drug sensitivity. We also constructed a ceRNA network and identified a lncRNA KCNQ1OT1/miR-328-3p/IL1B regulatory axis for LUSC. Conclusion: A bioinformatics method was performed to develop a pyroptosis-related prognostic signature containing four genes (IL6, IL1B, ELANE, and CASP4) in LUSC. We also constructed a ceRNA network and identified a lncRNA KCNQ1OT1/miR-328-3p/IL1B regulatory axis for LUSC. Further in vivo and in vitro studies should be conducted to verify these results.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Carcinoma de Células Escamosas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma de Células Escamosas/patologia , Variações do Número de Cópias de DNA , Regulação Neoplásica da Expressão Gênica , Humanos , Interleucina-6/metabolismo , Pulmão/patologia , Neoplasias Pulmonares/patologia , MicroRNAs/genética , Prognóstico , Piroptose/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Microambiente Tumoral
13.
Front Public Health ; 10: 842644, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35712312

RESUMO

Background: Men who have sex with men (MSM) are disproportionately affected by sexually transmitted infections (STIs). We sought to describe patterns of sexually transmitted co-infections and explore factors associated with increased acquisition of STIs among MSM. Methods: We enrolled MSM in Shenyang, China, between July and December 2020 to test for four STIs, including human papillomavirus (HPV), Chlamydia trachomatis (CT), Neisseria gonorrhoeae (NG), and Treponema pallidum (TP). Data regarding demographic and behavioral characteristics of participants were collected through a self-administered digital questionnaire. We adopted the ordinal logistic regression model to identify factors associated with acquiring more STIs. Results: Overall, 177 participants with completed test results for all four STIs were analyzed. These participants had a median age of 29.0 (interquartile range: 23.0-38.0) years. The prevalence of STI co-infections was 23.7% [42/177; 95% confidence interval (CI), 17.8%-30.8%], among which HPV/CT (47.1%) and HPV/CT/NG (50.0%) co-infection were the predominant types among participants with dual and multiple infections, respectively. Participants who had a higher educational background [adjusted odds ratio (aOR), 0.46; 95% CI, 0.24-0.85; P = 0.014] and had a history of STIs (aOR, 2.53; 95% CI, 1.24-5.18; P = 0.011) were positively associated with acquiring more STIs. Conclusions: MSM in Shenyang suffer a substantial burden of sexually transmitted co-infections. An optimized multi-STI integration strategy targeting prevention, surveillance, screening, and treatment is warranted to reduce the prevalence of sexually transmitted co-infections, especially in less-educated MSM.


Assuntos
Coinfecção , Gonorreia , Infecções por HIV , Infecções por Papillomavirus , Minorias Sexuais e de Gênero , Infecções Sexualmente Transmissíveis , Adulto , Chlamydia trachomatis , Coinfecção/epidemiologia , Estudos Transversais , Gonorreia/complicações , Gonorreia/epidemiologia , Infecções por HIV/epidemiologia , Homossexualidade Masculina , Humanos , Masculino , Infecções por Papillomavirus/complicações , Infecções por Papillomavirus/epidemiologia , Infecções Sexualmente Transmissíveis/complicações , Infecções Sexualmente Transmissíveis/epidemiologia , Adulto Jovem
14.
Eur Arch Otorhinolaryngol ; 279(11): 5089-5095, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-35732904

RESUMO

Allergic rhinitis (AR) is an immune-mediated inflammatory condition characterized by immune cell infiltration of the nasal mucosa, with symptoms of rhinorrhea, sneezing, nasal obstruction, and itchiness. Currently, common medication for AR is anti-inflammatory treatment including intranasal steroids, oral, or intranasal anti-histamines, and immunotherapy. These strategies are effective to the majority of patients with AR, but some patients under medication cannot achieve symptom relieve and suffer from bothersome side effects, indicating a demand for novel anti-inflammatory treatment as alternatives. Chemokines, a complex superfamily of small, secreted proteins, were initially recognized for their chemotactic effects on various immune cells. Chemokines constitute both physiological and inflammatory cell positioning systems and mediate cell localization to certain sites via interaction with their receptors, which are expressed on responding cells. Chemokines and their receptors participate in the sensitization, early phase response, and late phase response of AR by promoting inflammatory cell recruitment, differentiation, and allergic mediator release. In this review, we first systemically summarize chemokines and chemokine receptors that are important in AR pathophysiology and then discuss potential strategies targeting chemokines and their receptors for AR therapy.


Assuntos
Receptores de Quimiocinas , Rinite Alérgica , Anti-Inflamatórios/uso terapêutico , Quimiocinas/metabolismo , Quimiocinas/uso terapêutico , Humanos , Mucosa Nasal/metabolismo , Receptores de Quimiocinas/metabolismo , Receptores de Quimiocinas/uso terapêutico , Esteroides/uso terapêutico
15.
J Mol Graph Model ; 116: 108256, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-35764021

RESUMO

Pt(II) complexes play an important role in bioinorganic chemistry due to their antitumor activities. In the present study, we focused on building predictive models for the hydrophobicity of Pt(II) complexes. A five-parameter model, integrating frontier orbital energies (EHOMO, ELUMO) and descriptors derived from electrostatic potentials on molecular surface, was firstly constructed by using multiple linear regression (MLR) method. Mechanistic interpretations of the introduced descriptors were elucidated in terms of intermolecular interactions in the n-octanol/water partition system. Then, four up-to-date modeling methods, including support vector machine (SVM), least-squares support vector machine (LSSVM), random forest (RF) and Gaussian process (GP), were utilized to build the nonlinear models. Systematical validations including leave-one-out cross-validation, the validation for test set, as well as a very rigorous Monte Carlo cross-validation (MCCV) were performed to verify the reliability of the constructed models. The peak, median and integralRext2 values of the best GP model are 0.88, 0.86 and 0.84, respectively. The root mean squared errors for the test set (RMSEP) of the MLR, SVM, LSSVM and GP models fall in the range of 0.62-0.71. Although they are not superior to prior models built with the use of a number of descriptors, the results are satisfactory. Applicability domain of the model was evaluated.


Assuntos
Relação Quantitativa Estrutura-Atividade , Interações Hidrofóbicas e Hidrofílicas , Modelos Lineares , Reprodutibilidade dos Testes , Eletricidade Estática
16.
Front Immunol ; 13: 842831, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35320945

RESUMO

Natural killer (NK) cells play an important immunologic role, targeting tumors and virus-infected cells; however, NK cells do not impede the progression of human immunodeficiency virus (HIV) infection. In HIV infection, NK cells exhibit impaired functions and negatively regulate other immune cell responses, although NK cells can kill HIV-infected cells and thereby suppress HIV replication. Considerable recent research has emerged regarding NK cells in the areas of immune checkpoints, negative regulation, antibody-dependent cell-mediated cytotoxicity and HIV reservoirs during HIV infection; however, no overall summary of these factors is available. This review focuses on several important aspects of NK cells in relation to HIV infection, including changes in NK cell count, subpopulations, and immune checkpoints, as well as abnormalities in NK cell functions and NK cell negative regulation. The protective function of NK cells in inhibiting HIV replication to reduce the viral reservoir and approaches for enhancing NK cell functions are also summarized.


Assuntos
Infecções por HIV , HIV-1 , Citotoxicidade Celular Dependente de Anticorpos , Humanos , Células Matadoras Naturais
17.
Cell Rep ; 38(11): 110533, 2022 03 15.
Artigo em Inglês | MEDLINE | ID: mdl-35294870

RESUMO

Retroviral integration is mediated by a unique enzymatic process shared by all retroviruses and retrotransposons. During integration, double-stranded linear viral DNA is inserted into the host genome in a process catalyzed by viral-encoded integrase (IN). However, host cell defenses against HIV-1 integration are not clear. This study identifies ß-catenin-like protein 1 (CTNNBL1) as a potent inhibitor of HIV-1 integration via association with viral-encoded integrase (IN) and its cofactor, lens epithelium-derived growth factor/p75. CTNNBL1 overexpression blocks HIV-1 integration and inhibits viral replication, whereas CTNNBL1 depletion significantly upregulates HIV-1 integration into the genome of various target cells. Further, CTNNBL1 expression is downregulated in CD4+ T cells by activation, and CTNNBL1 depletion also facilitates HIV-1 integration in resting CD4+ T cells. Thus, host cells may employ CTNNBL1 to inhibit HIV-1 integration into the genome. This finding suggests a strategy for the treatment of HIV infections.


Assuntos
Infecções por HIV , Integrase de HIV , Soropositividade para HIV , HIV-1 , Proteínas Reguladoras de Apoptose/genética , DNA Viral/genética , Infecções por HIV/genética , Integrase de HIV/genética , Integrase de HIV/metabolismo , HIV-1/fisiologia , Humanos , Proteínas Nucleares/genética , Retroviridae , Integração Viral , Replicação Viral/fisiologia
18.
Nat Commun ; 13(1): 91, 2022 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35013181

RESUMO

Pursuing and developing effective methodologies to construct highly active catalytic sites to maximize the atomic and energy efficiency by material engineering are attractive. Relative to the tremendous researches of carbon-based single atom systems, the construction of bio-applicable single atom materials is still in its infancy. Herein, we propose a facile and general interfacial-confined coordination strategy to construct high-quality single-atom nanotherapeutic agent with Fe single atoms being anchored on defective carbon dots confined in a biocompatible mesoporous silica nanoreactor. Furthermore, the efficient energy conversion capability of silica-based Fe single atoms system has been demonstrated on the basis of the exogenous physical photo irradiation and endogenous biochemical reactive oxygen species stimulus in the confined mesoporous network. More importantly, the highest photothermal conversion efficiency with the mechanism of increased electron density and narrow bandgap of this single atom structure in defective carbon was proposed by the theoretical DFT calculations. The present methodology provides a scientific paradigm to design and develop versatile single atom nanotherapeutics with adjustable metal components and tune the corresponding reactions for safe and efficient tumor therapeutic strategy.


Assuntos
Carcinoma Hepatocelular/terapia , Óxido Ferroso-Férrico/química , Neoplasias Hepáticas/terapia , Nanopartículas Metálicas/administração & dosagem , Terapia Fototérmica/métodos , Nanomedicina Teranóstica/métodos , Animais , Carbono/química , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Feminino , Glutationa/química , Humanos , Luz , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , Nanopartículas Metálicas/química , Nanopartículas Metálicas/ultraestrutura , Camundongos , Camundongos Endogâmicos BALB C , Teoria Quântica , Espécies Reativas de Oxigênio/agonistas , Espécies Reativas de Oxigênio/metabolismo , Dióxido de Silício/química , Ensaios Antitumorais Modelo de Xenoenxerto
19.
Front Med (Lausanne) ; 8: 763564, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34869470

RESUMO

Background: Despite the insupportable burden caused by the human papillomavirus (HPV) and high vaccine acceptability, vaccination programs are not currently available for men who have sex with men (MSM). We aimed to assess HPV infection by examining the willingness for vaccination among MSM and cost-effectiveness of the Chinese 2-valent HPV vaccine. Methods: We recruited MSM in Shenyang, China between July and December 2020 to conduct anal HPV testing and an online survey regarding HPV-related knowledge and vaccine acceptability. We performed a cost-effectiveness analysis to evaluate the incremental cost-effectiveness ratios (ICERs) of the Chinese 2-valent HPV vaccine. Results: A total of 234 participants completed the online survey; of those, 203 were successfully tested for HPV. The median age was 30 years [interquartile range (IQR): 23-38 years]. Most participants had at least undergraduate education (136/234, 58.1%). The acceptability rate for the free HPV vaccine was 57.7% (135/234). The prevalence of HPV types 16 and 18 was 14.9% (18/121) and 26.8% (22/82) in the willing and unwilling to vaccinate groups, respectively (P > 0.05). The prevalence of high-risk HPV among participants aged <30 and ≥50 years was 48.6 and 38.9%, respectively. Using the Chinese per capita gross domestic product (GDP) as a threshold, the Chinese 2-valent HPV vaccine would be a "very cost-effective" strategy, with an ICER value of USD 4,411. This evidence showed that the Chinese 2-valent HPV vaccine was more cost-effective than other imported vaccines. Conclusions: Targeted strategies should be utilized in MSM with different rates of vaccine acceptability. A pilot HPV vaccination program based on the Chinese 2-valent HPV vaccine for MSM is urgently warranted to reduce the burden of HPV and anal cancer.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA