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1.
J Psychiatr Res ; 176: 198-204, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38878647

RESUMO

PURPOSE: Parents of children with cancer are exposed to risks of developing post-traumatic stress disorder (PTSD) symptoms, but few studies have explored PTSD symptoms of Chinese parents of children with acute lymphoblastic leukemia (ALL). Our study aimed to examine the association between social support and PTSD symptoms and to examine the mediating effect of positive expectations in this relationship among parents of children with ALL. METHODS: A cross-sectional study was conducted of consecutive parents of children with ALL in the Shengjing Hospital of China Medical University. A total of 177 parents eligible for this study completed questionnaires on PTSD symptoms, perceived social support, optimism and general self-efficacy anonymously. Asymptotic and resampling strategies were used to examine how positive expectations mediated the association between perceived social support and PTSD symptoms. RESULTS: Mean score of PTSD symptoms was 37.64 ± 14.44; 29.4% of the sample scored 44 and above, 19.8% scored 50 and above. After adjusting for covariates, perceived social support was negatively associated with the total score of PTSD symptoms (ß = -0.209, p < 0.01). Positive expectations were found to mediate the relationship between perceived social support and PTSD symptoms, especially for the symptoms of avoidance and hyperarousal. CONCLUSIONS: Optimism and general self-efficacy fully mediated the association between perceived social support and PTSD symptoms. Therefore, social support and positive expectations should be included in PTSD preventions and treatments targeting Chinese parents of children with ALL.

3.
Zhongguo Zhong Yao Za Zhi ; 49(2): 487-497, 2024 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-38403324

RESUMO

This study aims to explore the anti-inflammatory, vasodilation, and cardioprotective effects of the intestinal absorption liquids containing Xinshubao Tablets or single herbs, and to elucidate the potential mechanism based on network pharmacology. Western blot was then conducted to validate the expression changes of core proteins. Lipopolysaccharide(LPS)-stimulated RAW264.7 cells were used to observe the anti-inflammatory effect. The vasodilation activity was examined by the microvessel relaxation assay in vitro. Oxygen-glucose deprivation(OGD)-induced H9c2 cells were used to investigate the cardioprotective effect. The chemical components were retrieved from Herb databases and composition of Xinshubao Tablets drug-containing intestinal absorption solution. Drug targets were retrieved from SwissTargetPrediction databases. GeneCards was searched for the targets associated with the anti-inflammatory, vasodilation, and cardioprotective effects. The common targets shared by the drug and the effects were used to establish the protein-protein interaction(PPI) network, from which the core targets were obtained. Finally, the core targets were imported into Cytoscape 3.9.1 for Gene Ontology(GO) and Kyoto Encyclopedia of Genes and Genomes(KEGG) analyses. The anti-inflammatory experiment showed that both Xinshubao Tablets and the single herbs constituting this formula had anti-inflammatory effects. Curcumae Radix had the strongest inhibitory effect on the production of tumor necrosis factor-α(TNF-α), and Salviae Miltiorrhizae Radix et Rhizoma had the strongest inhibitory effect on the generation of interleukin-6(IL-6). Xinshubao Tablets, Curcumae Radix, and Crataegi Fructus had vasodilation effect, and Crataegi Fructus had the strongest effect. Xinshubao Tablets, Salviae Miltiorrhizae Radix et Rhizoma, Acanthopanacis Senticosi Radix et Rhizoma seu Caulis, and Paeoniae Radix Alba had cardioprotective effects, and Salviae Miltiorrhizae Radix et Rhizoma had the strongest cardioprotective effect. Network pharmacology results demonstrated that except the whole formula, Salviae Miltiorrhizae Radix et Rhizoma had the most components with anti-inflammatory effect, and Curcumae Radix had the most components with vasodilation and cardioprotective effects, followed by Salviae Miltiorrhizae Radix et Rhizoma. The nitric oxide synthase 3(NOS3) was predicted as the core target for the anti-inflammatory, vasodilation, and cardioprotective effects. Western blot results showed that Xinshubao Tablets significantly up-regulated the expression of NOS3 in OGD-induced H9c2 cells. GO enrichment analysis showed that the effects were mainly related to lipid exported from cell, regulation of blood pressure, and inflammatory response. KEGG pathway enrichment predicted AGE-RAGE and HIF-1 signaling pathways as the key pathways.


Assuntos
Medicamentos de Ervas Chinesas , Medicamentos de Ervas Chinesas/química , Farmacologia em Rede , Vasodilatação , Rizoma/química , Raízes de Plantas/química , Fator de Necrose Tumoral alfa , Medicina Tradicional Chinesa
4.
J Transl Med ; 22(1): 48, 2024 01 12.
Artigo em Inglês | MEDLINE | ID: mdl-38216927

RESUMO

BACKGROUND: Muscle-invasive bladder cancer (MIBC) is a highly aggressive disease with a poor prognosis. B cells are crucial factors in tumor suppression, and tertiary lymphoid structures (TLSs) facilitate immune cell recruitment to the tumor microenvironment (TME). However, the function and mechanisms of tumor-infiltrating B cells and TLSs in MIBC need to be explored further. METHODS: We performed single-cell RNA sequencing analysis of 11,612 B cells and 55,392 T cells from 12 bladder cancer patients and found naïve B cells, proliferating B cells, plasma cells, interferon-stimulated B cells and germinal center-associated B cells, and described the phenotype, gene enrichment, cell-cell communication, biological processes. We utilized immunohistochemistry (IHC) and immunofluorescence (IF) to describe TLSs morphology in MIBC. RESULTS: The interferon-stimulated B-cell subtype (B-ISG15) and germinal center-associated B-cell subtypes (B-LMO2, B-STMN1) were significantly enriched in MIBC. TLSs in MIBC exhibited a distinct follicular structure characterized by a central region of B cells resembling a germinal center surrounded by T cells. CellChat analysis showed that CXCL13 + T cells play a pivotal role in recruiting CXCR5 + B cells. Cell migration experiments demonstrated the chemoattraction of CXCL13 toward CXCR5 + B cells. Importantly, the infiltration of the interferon-stimulated B-cell subtype and the presence of TLSs correlated with a more favorable prognosis in MIBC. CONCLUSIONS: The study revealed the heterogeneity of B-cell subtypes in MIBC and suggests a pivotal role of TLSs in MIBC outcomes. Our study provides novel insights that contribute to the precision treatment of MIBC.


Assuntos
Estruturas Linfoides Terciárias , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Neoplasias da Bexiga Urinária/patologia , Linfócitos B , Prognóstico , Músculos/patologia , Interferons , Microambiente Tumoral
6.
Ann Nucl Med ; 38(4): 247-263, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38145430

RESUMO

INTRODUCTION: Functions of existing automatic module systems for synthesis of radiopharmaceuticals mainly focus on the radiolabeling of small molecules. There are few modules which have achieved full-automatic radiolabeling of non-metallic and metallic nuclides on small molecules, peptides, and antibody drugs. This study aimed to develop and test a full-automatic multifunctional module system for the safe, stable, and efficient production of radiopharmaceuticals. METHODS: According to characteristics of labeling process of radioactive drugs, using UG and Solidworks softwares, full-automatic cassette-based synthesis module system Mortenon M1 for synthesis of radiopharmaceuticals with various radionuclides, was designed and tested. Mortenon M1 has at least three significant highlights: the cassettes are disposable, and there is no need of manual cleaning; the synthesis method program is flexible and can be edited freely by users according to special needs; this module system is suitable for radiolabeling of both small-molecule and macromolecular drugs, with potentially various radionuclides including 18F, 64Cu, 68Ga, 89Zr, 177Lu, etc. By program control methods for certain drugs, Mortenon M1 was used for radiolabeling of both small-molecule drugs such as [68Ga]-FAPI-46 and macromolecular drugs such as [89Zr]-TROP2 antibody. Quality control assays for product purity were performed with radio-iTLC and radio-HPLC, and the radiotracers were confirmed for application in microPET imaging in xenograft tumor-bearing mouse models. RESULTS: Functional tests for Mortenon M1 module system were conducted, with [68Ga]-FAPI-46 and [89Zr]-TROP2 antibody as goal synthetic products, and it displayed that with the cassette modules, the preset goals could be achieved successfully. The radiolabeling synthesis yield was good ([68Ga]-FAPI-46, 70.63% ± 2.85%, n = 10; [89Zr]-TROP2, 82.31% ± 3.92%, n = 10), and the radiochemical purity via radio-iTLC assay of the radiolabeled products was above 99% after purification. MicroPET imaging results showed that the radiolabeled tracers had reasonable radioactive distribution in MDA-MB-231 and SNU-620 xenograft tumor-bearing mice, and the tumor targeted radiouptake was satisfactory for diagnosis. CONCLUSION: This study demonstrated that the full-automatic module system Mortenon M1 is efficient for radiolabeling synthesis of both small-molecule and macromolecular substrates. It may be helpful to reduce radiation exposure for safety, provide qualified radiolabeled products and reliable PET diagnosis, and ensure stable production and supply of radiopharmaceuticals.


Assuntos
Neoplasias , Compostos Radiofarmacêuticos , Humanos , Animais , Camundongos , Compostos Radiofarmacêuticos/química , Radioisótopos de Gálio/química , Radioisótopos/química , Peptídeos , Anticorpos
7.
J Colloid Interface Sci ; 656: 289-296, 2024 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-37995399

RESUMO

Currently, the development of economical and effective non-noble metal electrocatalysts is vital for advancing hydrogen evolution reaction (HER) and enabling its widespread applications. The customizable pore structure and enormous surface area of metal-organic frameworks (MOFs) have made them to become promising non-noble metal electrocatalysts for HER. However, MOFs have some challenges, including low conductivity and instability, which can result in them having high overpotentials and slow reaction kinetics in electrocatalytic processes. In this work, we present an innovative approach for synthesizing cost-effective and high-efficient Zr-MOF-derived pH-universal electrocatalysts for HER. It entails creating the interfaces of the electrocatalysts with suitable proportions of phosphide nanostructures. Zr-MOF/Ni2P@nickel foam (NF) electrodes with interface regulated by Ni2P nanostructures were successfully developed for high-efficient pH-universal HER electrocatalysts. The presence of Ni2P nanostructures with abundant active sites at the Zr-MOFs@NF interfaces boosted the electronic conductivity and local charge density of the hybrid electrocatalysts. This helped to improve their reaction kinetics and electrocatalytic activity. By optimizing the Ni2P amount, Zr-MOF/Ni2P@NF demonstrated impressive stability and superior HER activities, with a low overpotential of 149 mV (acidic electrolytes) and 143 mV (alkaline electrolytes) at 10 mA cm-2. The proven strategy in this work can be expanded to many types of MOF-based materials for wider practical applications.

8.
Environ Sci Technol ; 57(48): 20194-20205, 2023 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-37991390

RESUMO

Oil refinery activity can be an emission source of perfluoroalkyl and polyfluoroalkyl substances (PFAS) to the environment, while the contamination profiles in soils remain unknown. This study investigated 44 target PFAS in soil samples collected from an oil refinery in Southeastern China, identified novel PFAS, and characterized their behaviors by assessing their changes before and after employing advanced oxidation using a combination of nontarget analysis and a total oxidizable precursor (TOP) assay. Thirty-four target PFAS were detected in soil samples. Trifluoroacetic acid (TFA) and hexafluoropropylene oxide dimer acid (HFPO-DA) were the dominant PFAS. Twenty-three novel PFAS of 14 classes were identified, including 8 precursors, 11 products, and 4 stable PFAS characterized by the TOP assay. Particularly, three per-/polyfluorinated alcohols were identified for the first time, and hexafluoroisopropanol (HFIP) quantified up to 657 ng/g dw is a novel precursor for TFA. Bistriflimide (NTf2) potentially associated with an oil refinery was also reported for the first time in the soil samples. This study highlighted the advantage of embedding the TOP assay in nontarget analysis to reveal not only the presence of unknown PFAS but also their roles in environmental processes. Overall, this approach provides an efficient way to uncover contamination profiles of PFAS especially in source-impacted areas.


Assuntos
Fluorocarbonos , Poluentes Químicos da Água , Solo , Poluentes Químicos da Água/análise , China , Fluorocarbonos/análise , Oxirredução
9.
Eur J Med Chem ; 259: 115703, 2023 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-37556948

RESUMO

Aberrant FGFR4 signaling has been implicated in the development of several cancers, making FGFR4 a promising target for cancer therapy. Several FGFR4-selective inhibitors have been developed, yet none of them have been approved. Herein, we report a novel series of 1,6-naphthyridine-2-one derivatives as potent and selective inhibitors targeting FGFR4 kinase. Preliminary structure-activity relationship analysis was conducted. The screening cascades revealed that 19g was the preferred compound among the prepared series. 19g demonstrated excellent kinase selectivity and substantial cytotoxic effect against all tested colorectal cancer cell lines. 19g induced significant tumor inhibition in a HCT116 xenograft mouse model without any apparent toxicity. Notably, 19g exhibited excellent potency in disrupting the phosphorylation of FGFR4 and downstream signaling proteins mediated by FGF18 and FGF19. Compound 19g might be a potential antitumor drug candidate for the treatment of colorectal cancer.


Assuntos
Antineoplásicos , Neoplasias Colorretais , Neoplasias Hepáticas , Humanos , Animais , Camundongos , Transdução de Sinais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Linhagem Celular , Neoplasias Colorretais/tratamento farmacológico , Naftiridinas/farmacologia , Naftiridinas/uso terapêutico , Receptor Tipo 4 de Fator de Crescimento de Fibroblastos , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Hepáticas/tratamento farmacológico
10.
Planta Med ; 89(13): 1204-1214, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37459859

RESUMO

Leukemia, despite currently being one of the most lethal cancers worldwide, still lacks a focused treatment. The purpose of the present investigation was to evaluate the pharmacological effect of 1-methoxyerythrabyssin II, a pterocarpan identified in the roots of Lespedeza bicolor, on leukemic cells and to explore its underlying mechanism using a network pharmacology strategy. 1-Methoxyerythrabyssin II showed an antiproliferative effect in a concentration-dependent manner and exhibited a higher potency in human acute leukemia T cells (Jurkat). The G1 phase arrest induced by 1-methoxyerythrabyssin II was confirmed using a cell cycle assay, and the downregulation of CDK2 and cyclin D1 was observed using an immunoblot assay. Moreover, 1-methoxyerythrabyssin II-treated cells exhibited higher expression levels of LC3B, Atg-7, and Beclin 1 in addition to an enhanced fluorescence intensity in monodansylcadaverine staining, indicating autophagy induction by 1-methoxyerythrabyssin II. Furthermore, network pharmacology and molecular docking analyses revealed that the PI3K/Akt/mTOR pathway is a potential target of 1-methoxyerythrabyssin II in leukemic cells. In vitro assays further demonstrated that 1-methoxyerythrabyssin II promoted autophagy and suppressed cell proliferation by inhibiting the PI3K/Akt/mTOR pathway in leukemic cells. This discovery will contribute to the development of novel therapeutics and prophylactics against leukemia.

11.
Biomed Pharmacother ; 165: 115092, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37406512

RESUMO

Central nervous system (CNS) diseases are the leading cause of death worldwide. By performing compensatory functions and improving the inflammatory microenvironment, the transplantation of neural stem cells (NSCs) can promote functional recovery from brain injury, aging, brain tumours, and other diseases. However, the ability of NSCs to differentiate into neurons is limited, and they are associated with a risk of tumourigenicity. NSC-derived extracellular vesicles (NSC-EVs) can modulate the local microenvironment of the nervous system as well as distant neuronal functions. Thus, cell-free therapy may be a novel remedy for CNS disorders. This article reviews the characteristics, contents, and mechanisms of action of NSC-EVs as well as their roles and application prospects in various CNS diseases.


Assuntos
Lesões Encefálicas , Vesículas Extracelulares , Células-Tronco Neurais , Humanos , Neurônios/patologia , Lesões Encefálicas/patologia , Terapia Baseada em Transplante de Células e Tecidos
12.
Acta Biochim Biophys Sin (Shanghai) ; 55(5): 783-794, 2023 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-37232573

RESUMO

Bone marrow mesenchymal stem cell (BMSC)-derived exosomes are a promising therapeutic agent for human disease, but their effects on neural stem cells (NSCs) subject to spinal cord ischaemia-reperfusion injury (SCIRI) remain unknown. Here, we examine the impact of miR-199a-5p-enriched exosomes derived from BMSCs on NSC proliferation. We establish a rat model of aortic cross-clamping to induce SCIRI in vivo and a primary NSC model of oxygen-glucose deprivation/reoxygenation (OGD/R) to simulate SCIRI in vitro. CCK8, EdU, and BrdU assays are performed to evaluate the proliferation of NSCs. Hematoxylin and eosin (H&E) staining is used to determine the number of surviving neurons. The Basso, Beattie, and Bresnahan (BBB) scale and inclined plane test (IPT) are used to evaluate hind limb motor function. DiO-labelled exosomes are efficiently internalized by NSCs and increase ectopic amounts of miR-199a-5p, which promotes the proliferation of NSCs. In contrast, exosomes derived from miR-199a-5p-depleted BMSCs exert fewer beneficial effects. MiR-199a-5p targets and negatively regulates glycogen synthase kinase 3ß (GSK-3ß) and increases nuclear ß-catenin and cyclin D1 levels. miR-199a-5p inhibition reduces the total number of EdU-positive NSCs after OGD/R, but the GSK-3ß inhibitor CHIR-99021 reverses this effect. In vivo, intrathecal injection of BMSC-derived exosomes increases the proliferation of endogenous spinal cord NSCs after SCIRI. In addition, more proliferating NSCs are found in rats intrathecally injected with exosomes overexpressing miR-199a-5p. In summary, miR-199a-5p in BMSC-derived exosomes promotes NSC proliferation via GSK-3ß/ß-catenin signaling.


Assuntos
Exossomos , Células-Tronco Mesenquimais , MicroRNAs , Células-Tronco Neurais , Traumatismo por Reperfusão , Ratos , Humanos , Animais , MicroRNAs/genética , beta Catenina/genética , Glicogênio Sintase Quinase 3 beta/genética , Exossomos/genética , Proliferação de Células
13.
Eur J Med Chem ; 250: 115235, 2023 Mar 15.
Artigo em Inglês | MEDLINE | ID: mdl-36863226

RESUMO

The efficacy and resistance of cisplatin-based compounds are very intractable problems at present. This study reports a series of platinum(IV) compounds containing multiple-bond ligands, which exhibited better tumor cell inhibitory activity and antiproliferative and anti-metastasis activities than cisplatin. The meta-substituted compounds 2 and 5 were particularly excellent. Further research showed that compounds 2 and 5 possessed appropriate reduction potential and performed significantly better than cisplatin in cellular uptake, reactive oxygen species response, the up-regulation of apoptosis and DNA lesion-related genes, and drug-resistant cell activity. The title compounds exhibited better antitumor potential and fewer side effects than cisplatin in vivo. Multiple-bond ligands were introduced into cisplatin to form the title compounds in this study, which not only enhanced their absorption and overcame drug resistance but also demonstrated the potential to target mitochondria and inhibit the detoxification of tumor cells.


Assuntos
Antineoplásicos , Cisplatino , Cisplatino/farmacologia , Platina/farmacologia , Platina/química , Antineoplásicos/química , Resistencia a Medicamentos Antineoplásicos , Compostos Organoplatínicos/química , Mitocôndrias , Linhagem Celular Tumoral
14.
J Colloid Interface Sci ; 640: 820-828, 2023 Jun 15.
Artigo em Inglês | MEDLINE | ID: mdl-36905891

RESUMO

As a typical transition-metal sulfides (TMS), nickel disulfide (NiS2) has attracted great attention in terms of hydrogen evolution reaction (HER). Howbeit, owing to the poor conductivity, slow reaction kinetics and instability of NiS2, its HER activity is still necessary to be improved. In this work, we designed hybrid structures consisting of the nickel foam (NF) as a self-supporting electrode, NiS2 derived from the sulfuration of NF and Zr-MOF grown on the surface of NiS2@NF (Zr-MOF/NiS2@NF). Due to the synergistic effect between the different constituents, the obtained Zr-MOF/NiS2@NF demonstrates ideal electrochemical hydrogen evolution ability in acidic and alkalescent environment, reaching a standard current density of 10 mA cm-2 at overpotentials of 110 and 72 mV in 0.5 M H2SO4 and 1 M KOH electrolytes, respectively. What is more, it also maintains excellent electrocatalytic durability for 10 h in both electrolytes. This work could provide a useful guidance on effectively combining metal sulfide with MOF for high-performance HER electrocatalysts.

15.
FEBS Open Bio ; 13(4): 736-750, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36814419

RESUMO

Bladder urothelial carcinoma (BLCA) is a common malignant tumor of the human urinary system, and a large proportion of BLCA patients have a poor prognosis. Therefore, there is an urgent need to find more efficient and sensitive biomarkers for the prognosis of BLCA patients in clinical practice. RNA sequencing (RNA-seq) data and clinical information were obtained from The Cancer Genome Atlas, and 584 energy metabolism-related genes (EMRGs) were obtained from the Reactome pathway database. Cox regression analysis and least absolute shrinkage and selection operator analysis were applied to assess prognostic genes and build a risk score model. The estimate and cibersort algorithms were used to explore the immune microenvironment, immune infiltration, and checkpoints in BLCA patients. Furthermore, we used the Human Protein Atlas database and our single-cell RNA-seq datasets of BLCA patients to verify the expression of 13 EMRGs at the protein and single-cell levels. We constructed a risk score model; the area under the curve of the model at 5 years was 0.792. The risk score was significantly correlated with the immune markers M0 macrophages, M2 macrophages, CD8 T cells, follicular helper T cells, regulatory T cells, and dendritic activating cells. Furthermore, eight immune checkpoint genes were significantly upregulated in the high-risk group. The risk score model can accurately predict the prognosis of BLCA patients and has clinical application value. In addition, according to the differences in immune infiltration and checkpoints, BLCA patients with the most significant benefit can be selected for immune checkpoint inhibitor therapy.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Neoplasias da Bexiga Urinária/genética , Bexiga Urinária , Metabolismo Energético/genética , Algoritmos , Microambiente Tumoral/genética
16.
Brain Res Bull ; 195: 55-65, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36796652

RESUMO

Hypoxia and exosomes play important roles in the occurrence and development of glioma. While circRNAs are involved in biological processes of various tumors, the mechanism underlying exosome-dependent regulatory effects of circRNAs on the progression of glioma under hypoxia is unclear. Results suggested that circ101491 was overexpressed in tumor tissues and plasma exosomes of glioma patients, while the overexpression of circ101491 was closely related to the differentiation degree and TNM staging of the patients. Moreover, circ101491 overexpression promoted viability, invasion and migration of glioma cells both in vivo and in vitro; the above regulatory effects can be reversed by inhibition of circ101491 expression. Mechanistic studies revealed that circ101491 upregulated EDN1 expression through sponging miR-125b-5p, thus facilitating glioma progression. In summary, hypoxia could promote circ101491 overexpression in glioma cell-derived exosomes, and circ101491/miR-125b-5p/EDN1 regulatory axis might be implicated in the malignant progression of glioma.


Assuntos
Endotelina-1 , Glioma , MicroRNAs , Humanos , Linhagem Celular Tumoral , Proliferação de Células , Glioma/metabolismo , Hipóxia , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Circular/genética , Endotelina-1/metabolismo
17.
Eur J Med Chem ; 248: 115088, 2023 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-36623329

RESUMO

New efficient antimicrobial agents are urgently needed to combat invasive multidrug-resistant pathogens infections. Structurally unique benzenesulfonyl thiazoloimines (BSTIs) were exploited as novel potential antibacterial victors to confront terrific drug resistance. Some developed BSTIs exerted effectively antimicrobial efficacy against the tested strains. Notably, 2-pyridyl BSTI 14d exhibited good antibacterial activity against E. faecalis with MIC value of 1 µg/mL, which was superior to sulfathiazole and norfloxacin. The most active compound 14d not only showed rapid bactericidal properties and impeded E. faecalis biofilm formation to effectually relieve the development of drug resistance, but also performed low toxicity toward human red blood cells, human normal squamous epithelial cells and human non-neoplastic colon epithelial cells. Mechanistic investigation demonstrated that molecule 14d could exert efficient membrane destruction leading to the leakage of intracellular materials and metabolism inhibition, cause oxidative damage of E. faecalis through accumulation of excess reactive oxygen species and reduction of glutathione activity, and intercalate into DNA to hinder replication of DNA. Molecular docking indicated that the formation of 14d-dihydrofolate synthetase supramolecular complex could hinder the function of this enzyme. ADME analysis displayed that compound 14d possessed promising pharmacokinetic properties. These findings suggested that the newly developed benzenesulfonyl thiazoloimines with multitargeting antibacterial potential provided a new possibility for evading resistance.


Assuntos
Antibacterianos , Anti-Infecciosos , Humanos , Antibacterianos/farmacologia , Enterococcus faecalis , Simulação de Acoplamento Molecular , Norfloxacino/farmacologia , Anti-Infecciosos/farmacologia , DNA/farmacologia , Testes de Sensibilidade Microbiana
18.
Cell Mol Neurobiol ; 43(5): 1799-1816, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36308642

RESUMO

Normoxia is defined as an oxygen concentration of 20.9%, as in room air, whereas hypoxia refers to any oxygen concentration less than this. Any physiological oxygen deficiency or tissue oxygen deficiency relative to demand is called hypoxia. Neural stem cells (NSCs) are multipotent stem cells that can differentiate into multiple cell lines such as neurons, oligodendrocytes, and astrocytes. Under hypoxic conditions, the apoptosis rate of NSCs increases remarkably in vitro or in vivo. However, some hypoxia promotes the proliferation and differentiation of NSCs. The difference is related to the oxygen concentration, the duration of hypoxia, the hypoxia tolerance threshold of the NSCs, and the tissue source of the NSCs. The main mechanism of hypoxia-induced proliferation and differentiation involves an increase in cyclin and erythropoietin concentrations, and hypoxia-inducible factors play a key role. Multiple molecular pathways are activated during hypoxia, including Notch, Wnt/ß-catenin, PI3K/Akt, and altered microRNA expression. In addition, we review the protective effect of exogenous NSCs transplantation on ischemic or anoxic organs, the therapeutic potential of hypoxic preconditioning on exogenous NSCs and clinical application of NSCs.


Assuntos
Células-Tronco Neurais , Fosfatidilinositol 3-Quinases , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proliferação de Células , Células-Tronco Neurais/metabolismo , Diferenciação Celular/fisiologia , Hipóxia/metabolismo , Hipóxia Celular/fisiologia , Oxigênio/farmacologia , Oxigênio/metabolismo , Células Cultivadas
19.
Biomolecules ; 12(11)2022 11 11.
Artigo em Inglês | MEDLINE | ID: mdl-36421685

RESUMO

The purpose of this study was to explore the relationship between bladder urothelial cancer (BLCA) and immunity, to screen prognosis-related immune genes (PIGs), and to construct an immune-related prognosis model (IRPM). We processed the relevant data of The Cancer Genome Atlas (TCGA-BLCA) and GSE13507 using R software and Perl. We divided BLCA into high-immunity and low-immunity subtypes. There were significant differences in the two subtypes. In addition, we identified 13 PIGs of BLCA by jointly analyzing the gene expression data and survival information of GSE13507 and TCGA-BLCA, and constructed IRPM through nine of them. The low-risk group had better survival outcome than the high-risk group. We also constructed a nomogram based on clinicopathological information and risk scores of the patients. Moreover, the prognosis of BLCA patients was significantly impacted by the expression of almost every gene used to calculate the risk score. The result of real-time fluorescence quantitative polymerase chain reaction revealed that all the genes used to calculate the risk score were differentially expressed between BLCA and adjacent normal tissues, except PDGFRA. Our research provided potential targets for the treatment of BLCA and a reference for judging the prognosis of BLCA.


Assuntos
Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Prognóstico , Bexiga Urinária/metabolismo , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Neoplasias da Bexiga Urinária/metabolismo
20.
World J Gastrointest Surg ; 14(9): 1082-1085, 2022 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-36185556

RESUMO

Acute portal venous system thrombosis (PVST) can cause acute mesenteric ischemia and even intestinal infarction, which are potentially fatal, and requires recanalization in a timely fashion. Herein, we report a 56-year-old man with acute non-cirrhotic symptomatic extensive PVST who achieved portal vein recanalization after systemic thrombolysis combined with anticoagulation. Initially, anticoagulation with enoxaparin sodium for 4 d was ineffective, and then systemic thrombolysis for 7 d was added. After that, his abdominal pain completely disappeared, and portal vein system vessels became gradually patent. Long-term anticoagulation therapy was maintained. In conclusion, 7-d systemic thrombolysis may be an effective and safe choice of treatment for acute symptomatic extensive PVST which does not respond to anticoagulation therapy.

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