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1.
Phytother Res ; 38(5): 2128-2153, 2024 May.
Article in English | MEDLINE | ID: mdl-38400575

ABSTRACT

Thrombotic disorders, such as myocardial infarction and stroke, are the leading cause of death in the global population and have become a health problem worldwide. Drug therapy is one of the main antithrombotic strategies, but antithrombotic drugs are not completely safe, especially the risk of bleeding at therapeutic doses. Recently, natural products have received widespread interest due to their significant efficacy and high safety, and an increasing number of studies have demonstrated their antithrombotic activity. In this review, articles from databases, such as Web of Science, PubMed, and China National Knowledge Infrastructure, were filtered and the relevant information was extracted according to predefined criteria. As a result, more than 100 natural products with significant antithrombotic activity were identified, including flavonoids, phenylpropanoids, quinones, terpenoids, steroids, and alkaloids. These compounds exert antithrombotic effects by inhibiting platelet activation, suppressing the coagulation cascade, and promoting fibrinolysis. In addition, several natural products also inhibit thrombosis by regulating miRNA expression, anti-inflammatory, and other pathways. This review systematically summarizes the natural products with antithrombotic activity, including their therapeutic effects, mechanisms, and clinical applications, aiming to provide a reference for the development of new antithrombotic drugs.


Subject(s)
Biological Products , Fibrinolytic Agents , Thrombosis , Biological Products/pharmacology , Biological Products/therapeutic use , Humans , Thrombosis/drug therapy , Fibrinolytic Agents/pharmacology , Fibrinolytic Agents/therapeutic use , Animals , Platelet Activation/drug effects , Anti-Inflammatory Agents/pharmacology , Anti-Inflammatory Agents/therapeutic use
2.
J Microencapsul ; 41(4): 296-311, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38709162

ABSTRACT

AIMS: To construct the microemulsion delivery system (ME) loading ATSO and NA and study their physicochemical characteristics to enhance their stability and water solubility. METHODS: By plotting ternary phase diagrams, the composition and proportions of the MEs were determined. The physicochemical characteristics and stability of MEs were evaluated by mean diameter, polydispersity index (PDI), pH, electrical conductivity, transmission electron microscopy (TEM), rheological behaviour measurement, and phase inversion temperature (PIT). RESULTS: The MEs was composed with EL-40 as a surfactant and specifically with the addition of ethanol as a cosurfactant in NA-loaded ME. The mean diameters of ATSO-loaded ME and NA-loaded ME were 39.65 ± 0.24 nm and 32.90 ± 2.65 nm, and PDI were 0.49 ± 0.01 and 0.28 ± 0.14, respectively. The TEM confirmed the spherical and smooth morphology of MEs. The rheological results indicated that MEs are dilatant fluids with the advantages of low viscosity, high fluidity, and tolerance to temperature fluctuations. The mean diameter and PDI of MEs showed no significant change after storage at 25 °C for 28 days and centrifugation. CONCLUSION: The prepared microemulsions could expand the application prospects of ATSO and NA products in cosmetics, medicine, foods and other fields.


Subject(s)
Emulsions , Plant Oils , Rheology , Emulsions/chemistry , Plant Oils/chemistry , Acer/chemistry , Fatty Acids/chemistry , Seeds/chemistry , Surface-Active Agents/chemistry , Drug Stability , Viscosity
3.
Molecules ; 29(10)2024 May 16.
Article in English | MEDLINE | ID: mdl-38792216

ABSTRACT

Fullerene-based amphiphiles are new types of monomers that form self-assemblies with profound applications. The conical fullerene amphiphiles (CFAs) have attracted attention for their uniquely self-assembled structures and have opened up a new field for amphiphile research. The CFAs and CFAs with different substances embedded in cavities are designed and their self-assembly behaviors are investigated using molecular dynamics (MD) simulations. The surface and internal structures of the micelles are analyzed from various perspectives, including micelle size, shape, and solvent-accessible surface area (SASA). The systems studied are all oblate micelles. In comparison, embedding Cl- or embedding Na+ in the cavities results in larger micelles and a larger deviation from the spherical shape. Two typical configurations of fullerene surfactant micelles, quadrilateral plane and tetrahedral structure, are presented. The dipole moments of the fullerene molecules are also calculated, and the results show that the embedded negatively charged Cl- leads to a decrease in the polarity of the pure fullerene molecules, while the embedded positively charged Na+ leads to an increase.

4.
Environ Sci Technol ; 57(51): 21715-21726, 2023 Dec 26.
Article in English | MEDLINE | ID: mdl-38079577

ABSTRACT

Microbial methane oxidation coupled to a selenate reduction process has been proposed as a promising solution to treat contaminated water, yet the underlying microbial mechanisms are still unclear. In this study, a novel methane-based membrane bioreactor system integrating hollow fiber membranes for efficient gas delivery and ultrafiltration membranes for biomass retention was established to successfully enrich abundant suspended cultures able to perform methane-dependent selenate reduction under oxygen-limiting conditions. The microbial metabolic mechanisms were then systematically investigated through a combination of short-term batch tests, DNA-based stable isotope probing (SIP) microcosm incubation, and high-throughput sequencing analyses of 16S rRNA gene and functional genes (pmoA and narG). We confirmed that the methane-supported selenate reduction process was accomplished by a microbial consortia consisting of type-II aerobic methanotrophs and several heterotrophic selenate reducers. The mass balance and validation tests on possible intermediates suggested that methane was partially oxidized into acetate under oxygen-limiting conditions, which was consumed as a carbon source for selenate-reducing bacteria. High-throughput 16S rRNA gene sequencing, DNA-SIP incubation with 13CH4, and subsequent functional gene (pmoA and narG) sequencing results collectively proved that Methylocystis actively executed partial methane oxidation and Acidovorax and Denitratisoma were dominant selenate-reducing bacteria, thus forming a syntrophic partnership to drive selenate reduction. The findings not only advance our understanding of methane oxidation coupled to selenate reduction under oxygen-limiting conditions but also offer useful information on developing methane-based biotechnology for bioremediation of selenate-contaminated water.


Subject(s)
Bacteria , Methane , Selenic Acid/metabolism , RNA, Ribosomal, 16S/genetics , Bacteria/genetics , Oxidation-Reduction , Isotopes/metabolism , Bioreactors , Oxygen , Water
5.
Metab Brain Dis ; 38(6): 2065-2075, 2023 08.
Article in English | MEDLINE | ID: mdl-37148433

ABSTRACT

Neuroinflammation contributes to the pathogenesis of depression. Inulin-type oligosaccharides of Morinda officinalis (IOMO) exert antidepressant-like effects in rodents and patients with depression, while the underlying mechanisms remain unclear. This study used chronic restraint stress (CRS) and lipopolysaccharide (LPS) to induce depression-like behaviors in mice. Western blotting and ELISA analysis were used to investigate the effects of IOMO on inflammatory cytokine levels. Immunofluorescence analysis was used to investigate the effects of IOMO on hippocampal NLRP3 inflammasome and microglial cells. The results suggested that 6 weeks of CRS induced significant depression-like behaviors based on the sucrose preference test (SPT), tail suspension test (TST), and forced swimming test (FST), which were accompanied by increases in the expression of IL-6 and the activation of hippocampal microglial cells. Chronic treatment with IOMO (25 mg/kg, i.g.) for 28 days significantly reversed these depression-like behaviors and inhibited the activation of microglial cells. Furthermore, LPS (0.5 mg/kg, i.p.) also significantly induced depression-like behaviors in the TST, FST, and novelty-suppressed feeding test (NSFT), as well as increased the expression of IL-1ß and caspase-1, and activated the microglial cells and the NLRP3 inflammasome in the hippocampus. Treatment with IOMO for 9 days significantly reversed these depression-like behaviors and normalized the LPS-induced activation of the microglial cells and NLRP3 inflammasome. Taken together, these results suggested that IOMO exerted antidepressant-like effects via hippocampal microglial NLRP3 inflammasome mediation followed by caspase-1 inhibition and the production of IL-1ß. These findings provide a basis for developing new antidepressants targeting the microglial NLRP3 inflammasome.


Subject(s)
Inflammasomes , Morinda , Mice , Animals , Inflammasomes/metabolism , Inulin/pharmacology , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Morinda/metabolism , Lipopolysaccharides/pharmacology , Antidepressive Agents/pharmacology , Antidepressive Agents/therapeutic use , Microglia/metabolism , Hippocampus/metabolism , Oligosaccharides/pharmacology , Inflammation/metabolism , Caspases/metabolism , Depression/chemically induced , Stress, Psychological/complications
6.
Biotechnol Lett ; 45(10): 1355-1364, 2023 Oct.
Article in English | MEDLINE | ID: mdl-37486554

ABSTRACT

PURPOSE: In our previous study, we constructed a one-pot multi-enzyme system for rare ketoses synthesis based on L-rhamnulose-1-phosphate aldolase (RhaD) from accessible glycerol in vitro. To eliminate tedious purification of enzymes, a facile Escherichia coli whole-cell cascade platform was established in this study. METHODS: To enhance the conversion rate, the reaction conditions, substrate concentrations and expressions of related enzymes were extensively optimized. RESULTS: The biosynthetic route for the cascade synthesis of rare ketoses in whole cells was successfully constructed and three rare ketoses including D-allulose, D-sorbose and L-fructose were produced using glycerol and D/L-glyceraldehyde (GA). Under optimized conditions, the conversion rates of rare ketoses were 85.0% and 93.0% using D-GA and L-GA as the receptor, respectively. Furthermore, alditol oxidase (AldO) was introduced to the whole-cell system to generate D-GA from glycerol, and the total production yield of D-sorbose and D-allulose was 8.2 g l-1 only from the sole carbon source glycerol. CONCLUSION: This study demonstrates a feasible and cost-efficient method for rare sugars synthesis and can also be applied to the green synthesis of other value-added chemicals from glycerol.


Subject(s)
Ketoses , Sorbose , Sorbose/chemistry , Glycerol/metabolism , Glyceraldehyde/chemistry , Glyceraldehyde/metabolism
7.
Aging Ment Health ; 27(2): 357-371, 2023 02.
Article in English | MEDLINE | ID: mdl-35315703

ABSTRACT

OBJECTIVES: The International Classification of Functioning, Disability and Health (ICF) endorsed by the World Health Organization provides a conceptual framework for describing functioning and disability based on a biopsychosocial model. Although dementia is one of the leading causes of disability, yet little is known on the extent to how the ICF has been utilized in dementia research and practice. The study aimed to examine and map the current applications of the ICF with dementia from a body of earlier studies and to explore the potential use in person-centred dementia care. METHODS: The Arksey and O'Malley framework was used to guide the searching, selecting, and synthesizing process. The scoping review was reported following The Preferred Reporting Items for Systematic reviews and Meta-Analyses extension for Scoping Review (PRISMA-ScR) guidelines. RESULTS: A total of 34 studies were included. The applications of ICF were classified into 4 themes: (1) in clinical practice and the education of health professionals (n = 20); (2) community support services and income support (n = 3); (3) population-based, census, or survey data (n = 10); (4) advocacy and empowerment purposes (n = 1). CONCLUSION: The ICF has made a major impact on dementia in clinical settings. Findings strongly support applying the ICF to person-centered dementia care. In the future, more empirical studies are needed to expand the scope of ICF use in dementia research and practice.


Subject(s)
Dementia , Disabled Persons , Humans , Dementia/therapy , Disability Evaluation , Health Personnel , International Classification of Functioning, Disability and Health , World Health Organization
8.
Int J Mol Sci ; 24(15)2023 Aug 05.
Article in English | MEDLINE | ID: mdl-37569852

ABSTRACT

Constant efforts are being made to develop methods for improving cancer immunotherapy, including cytokine-induced killer (CIK) cell therapy. Numerous heat shock protein (HSP) 90 inhibitors have been assessed for antitumor efficacy in preclinical and clinical trials, highlighting their individual prospects for targeted cancer therapy. Therefore, we tested the compatibility of CIK cells with HSP90 inhibitors using Burkitt's lymphoma (BL) cells. Our analysis revealed that CIK cytotoxicity in BL cells was augmented in combination with independent HSP90 inhibitors 17-DMAG (17-dimethylaminoethylamino-17-demethoxygeldanamycin) and ganetespib. Interestingly, CIK cell cytotoxicity did not diminish after blocking with NKG2D (natural killer group 2, member D), which is a prerequisite for their activation. Subsequent analyses revealed that the increased expression of Fas on the surface of BL cells, which induces caspase 3/7-dependent apoptosis, may account for this effect. Thus, we provide evidence that CIK cells, either alone or in combination with HSP90 inhibitors, target BL cells via the Fas-FasL axis rather than the NKG2D pathway. In the context of clinical relevance, we also found that high expression of HSP90 family genes (HSP90AA1, HSP90AB1, and HSP90B1) was significantly associated with the reduced overall survival of BL patients. In addition to HSP90, genes belonging to the Hsp40, Hsp70, and Hsp110 families have also been found to be clinically significant for BL survival. Taken together, the combinatorial therapy of CIK cells with HSP90 inhibitors has the potential to provide clinical benefits to patients with BL.


Subject(s)
Antineoplastic Agents , Burkitt Lymphoma , Cytokine-Induced Killer Cells , Humans , Burkitt Lymphoma/drug therapy , Cytokine-Induced Killer Cells/metabolism , NK Cell Lectin-Like Receptor Subfamily K/genetics , Antineoplastic Agents/pharmacology , Heat-Shock Proteins/therapeutic use , Cell Line, Tumor
9.
Int J Mol Sci ; 24(5)2023 Feb 21.
Article in English | MEDLINE | ID: mdl-36901718

ABSTRACT

Very-long-chain alkane plays an important role as an aliphatic barrier. We previously reported that BnCER1-2 was responsible for alkane biosynthesis in Brassica napus and improved plant tolerance to drought. However, how the expression of BnCER1-2 is regulated is still unknown. Through yeast one-hybrid screening, we identified a transcriptional regulator of BnCER1-2, BnaC9.DEWAX1, which encodes AP2\ERF transcription factor. BnaC9.DEWAX1 targets the nucleus and displays transcriptional repression activity. Electrophoretic mobility shift and transient transcriptional assays suggested that BnaC9.DEWAX1 repressed the transcription of BnCER1-2 by directly interacting with its promoter. BnaC9.DEWAX1 was expressed predominantly in leaves and siliques, which was similar to the expression pattern of BnCER1-2. Hormone and major abiotic stresses such as drought and high salinity affected the expression of BnaC9.DEWAX1. Ectopic expression of BnaC9.DEWAX1 in Arabidopsis plants down-regulated CER1 transcription levels and resulted in a reduction in alkanes and total wax loads in leaves and stems when compared with the wild type, whereas the wax depositions in the dewax mutant returned to the wild type level after complementation of BnaC9.DEWAX1 in the mutant. Moreover, both altered cuticular wax composition and structure contribute to increased epidermal permeability in BnaC9.DEWAX1 overexpression lines. Collectively, these results support the notion that BnaC9.DEWAX1 negatively regulates wax biosynthesis by binding directly to the BnCER1-2 promoter, which provides insights into the regulatory mechanism of wax biosynthesis in B. napus.


Subject(s)
Brassica napus , Plant Proteins , Alkanes/metabolism , Arabidopsis/genetics , Arabidopsis Proteins/genetics , Brassica napus/genetics , Gene Expression , Gene Expression Regulation, Plant , Plant Leaves/metabolism , Waxes/metabolism
10.
Molecules ; 28(17)2023 Aug 31.
Article in English | MEDLINE | ID: mdl-37687215

ABSTRACT

Glycosylation is an important post-translational modification of proteins, contributing to protein function, stability and subcellular localization. Fungal immunomodulatory proteins (FIPs) are a group of small proteins with notable immunomodulatory activity, some of which are glycoproteins. In this study, the impact of glycosylation on the bioactivity and biochemical characteristics of FIP-nha (from Nectria haematococca) is described. Three rFIP-nha glycan mutants (N5A, N39A, N5+39A) were constructed and expressed in Pichia pastoris to study the functionality of the specific N-glycosylation on amino acid N5 and N39. Their protein characteristics, structure, stability and activity were tested. WT and mutants all formed tetramers, with no obvious difference in crystal structures. Their melting temperatures were 82.2 °C (WT), 81.4 °C (N5A), 80.7 °C (N39A) and 80.1 °C (N5+39A), indicating that glycosylation improves thermostability of rFIP-nha. Digestion assays showed that glycosylation on either site improved pepsin resistance, while 39N-glycosylation was important for trypsin resistance. Based on the 3D structure and analysis of enzyme cleavage sites, we conclude that glycosylation might interfere with hydrolysis via increasing steric hindrance. WT and mutants exerted similar bioactivity on tumor cell metabolism and red blood cells hemagglutination. Taken together, these findings indicate that glycosylation of FIP-nha impacts its thermostability and digestion resistance.


Subject(s)
Fusarium , Peptide Hydrolases , Glycosylation , Proteolysis , Fungal Proteins/genetics
11.
Zhongguo Zhong Yao Za Zhi ; 48(19): 5315-5325, 2023 Oct.
Article in Zh | MEDLINE | ID: mdl-38114121

ABSTRACT

This study aims to investigate the effects and the molecular mechanism of Huangdi Anxiao Capsules(HDAX)-containing serum in protecting the rat adrenal pheochromocytoma(PC12) cells from diabetes-associated cognitive dysfunction induced by high glucose and whether the mechanism is related to the regulation of NOD-like receptor thermal protein domain associated protein 3(NLRP3)-mediated pyroptosis. The PC12 cell model of diabetes-associated cognitive dysfunction induced by high glucose was established and mcc950 was used to inhibit NLRP3. PC12 cells were randomized into control, model, HDAX-containing serum, mcc950, and HDAX-containing serum+mcc950 groups. Methyl thiazolyl tetrazolium(MTT) assay was employed to determine the viability, and Hoechst 33258/PI staining to detect pyroptosis of PC12 cells. Enzyme-linked immunosorbent assay(ELISA) was employed to measure the levels of interleukin-1 beta(IL-1ß) and IL-18. Western blot was employed to determine the protein levels of postsynaptic density protein 95(PSD-95), NLRP3, apoptosis-associated speck-like protein containing a CARD(ASC), gasdermin D(GSDMD), GSDMD-N, and cleaved cysteinyl aspartate specific proteinase-1(caspase-1), and RT-PCR to determine the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1. The immunofluorescence assay was adopted to measure the levels and distribution of NLRP3 and GSDMD-N in PC12 cells. Compared with the control group, the model group showed decreased cell proliferation, increased PI positive rate, down-regulated protein level of PSD-95, up-regulated protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1, up-regulated mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and elevated levels of IL-1ß and IL-18. Compared with the model group, HDAX-containing serum, mcc950, and the combination of them improved cell survival rate and morphology, decreased the PI positive rate, down-regulated the protein levels of NLRP3, ASC, GSDMD-N, GSDMD, and cleaved caspase-1 and the mRNA levels of NLRP3, ASC, GSDMD, and caspase-1, and promoted the secretion of IL-1ß and IL-18. The findings demonstrated that HDAX-containing serum can inhibit the pyroptosis-mediated by NLRP3 and protect PC12 cells from the cognitive dysfunction induced by high glucose.


Subject(s)
Diabetes Mellitus , NLR Family, Pyrin Domain-Containing 3 Protein , Rats , Animals , NLR Family, Pyrin Domain-Containing 3 Protein/genetics , NLR Family, Pyrin Domain-Containing 3 Protein/metabolism , Interleukin-18 , Pyroptosis/physiology , Caspases , Glucose , RNA, Messenger
12.
Mod Pathol ; 35(9): 1181-1192, 2022 09.
Article in English | MEDLINE | ID: mdl-35641658

ABSTRACT

Lung adenocarcinoma (LUAD) is a heterogeneous disease. Our study aimed to understand the unique molecular features of preinvasive to invasive LUAD subtypes. We retrospectively analyzed the clinical, histopathological, and molecular data of 3,254 Chinese patients with preinvasive lesions (n = 252), minimally invasive adenocarcinomas (n = 479), and invasive LUAD (n = 2,523). Molecular data were elucidated using a targeted 68-gene next-generation sequencing panel. Our findings revealed four preinvasive lesion-predominant gene mutations, including MAP2K1 insertion-deletions (indels), BRAF non-V600E kinase mutations, and exon 20 insertions (20ins) in both EGFR and ERBB2, which we referred to as mutations enriched in AIS (MEA). The detection rate of MEA in invasive tumors was relatively lower. MAP2K1 missense mutations, which were likely passenger mutations, co-occurred with oncogenic driver mutations, while small indels were mutually exclusive from other genes regardless of the invasion level. BRAF non-V600E kinase-mutant invasive adenocarcinomas (IAC) had significantly higher mutation rates in tumor suppressor genes but lower frequency of co-occurring oncogenic driver mutations than non-kinase-mutant IAC, suggesting the potential oncogenic activity of BRAF non-V600E kinase mutations albeit weaker than BRAF V600E. Moreover, similar to the extremely low frequency of MAP2K1 indels in IAC, BRAF non-V600E kinase domain mutations co-occurring with TSC1 mutations were exclusively found in preinvasive lesions. Compared with EGFR L858R and exon 19 deletion, patients with preinvasive lesions harboring 20ins in either EGFR or ERBB2 were significantly younger, while those with IAC had similar age. Furthermore, our study demonstrated distinct mutational features for subtypes of oncogene mutations favored by different invasion patterns in adenocarcinomas. In conclusion, our data demonstrate distinct mutational features between preinvasive lesions and invasive tumors with MEA, suggesting the involvement of MEA in the early stages of tumorigenesis. Further pre-clinical studies are required to establish the role of these genes in the malignant transformation of LUAD.


Subject(s)
Adenocarcinoma of Lung , Adenocarcinoma , Lung Neoplasms , Adenocarcinoma/genetics , Adenocarcinoma/pathology , Adenocarcinoma/surgery , Adenocarcinoma of Lung/genetics , Adenocarcinoma of Lung/surgery , Carcinogenesis , Humans , Lung Neoplasms/genetics , Lung Neoplasms/pathology , Lung Neoplasms/surgery , Mutation , Proto-Oncogene Proteins B-raf/genetics , Retrospective Studies
13.
Cancer Invest ; 40(8): 663-674, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35770858

ABSTRACT

BACKGROUND: Like other cancers, considerable effort has been made in acute myeloid leukemia (AML) to identify prognostic genes and long noncoding RNAs (lncRNAs) with their potential clinical applications. However, to date, no integrated prognostic model has been developed that combines both gene expression and lncRNAs as a singular approach in AML. METHOD: Comprehensive bioinformatic approaches (Weighted gene co-expression network analysis, Univariate Cox regression analyses, Pearson correlation, LASSO-Cox regression, Wilcoxon test) were used to construct the signature and to define high- and low-risk groups in AML datasets. ESTIMATE and CIBERSORT algorithms were applied to investigate the potential impact of infiltrating immune cells based on the obtained signature in tumor microenvironment. In addition, gene ontology (GO) and KEGG enrichment were applied to explore the potential function of the signature. RESULTS: Herein, we focused on immune-related genes (IRGs) and immune-related long noncoding RNAs (IRlncRNAs) and constructed an integrated prognostic immunorelevant signature in AML. The obtained signature exhibit five IRGs (DAXX, PSMB8, CSRP1, RAC2 and PTPN6) and one IRlncRNA (AC080037.2) and is strictly associated with age and FAB (French-American-British classification). Importantly, the high-risk AML group (defined by the signature) correlated positively with three types of scores (immune score, stroma score, and ESTIMATE score). We also identified a few immune cells (resting mast cells and monocytes) potentially involved in the correlation between signature and survival of AML patients. The prognostic ability of the obtained signature was tested in the training cohort and then validated in both test and total cohorts. The pathway enrichment analysis confirmed the possible immune- related role of the signature. CONCLUSION: We constructed an integrated prognostic signature comprising five immune-related protein-coding genes (IRPCG) (DAXX, PSMB8, CSRP1, RAC2, and PTPN6) and one immune-related lncRNA (AC080037.2) that may serve as potential biomarkers for predicting survival and further stratifying AML patients.


Subject(s)
Leukemia, Myeloid, Acute , RNA, Long Noncoding , Biomarkers, Tumor/metabolism , Humans , Leukemia, Myeloid, Acute/genetics , Prognosis , RNA, Long Noncoding/genetics , RNA, Long Noncoding/metabolism , Tumor Microenvironment/genetics
14.
Kidney Blood Press Res ; 47(4): 247-255, 2022.
Article in English | MEDLINE | ID: mdl-35038704

ABSTRACT

BACKGROUND: Diabetic nephropathy is a common complication of the kidneys induced by diabetes and is the main cause of end-stage renal disease. MicroRNA-494-3p was reported to be upregulated in renal tissues collected from db/db mice, but its specific role in diabetic nephropathy was still unclear. This study aimed to explore the effect of miR-494-3p on renal fibrosis using an in vitro cell model of diabetic nephropathy. METHODS: After human renal tubular epithelial cells (HK-2) were treated with high glucose (HG), the viability and apoptosis of cells were examined by CCK-8 assays and flow cytometry analyses. Additionally, protein levels of fibronectin, collagen I, collagen III, collagen IV, and epithelial-mesenchymal transition (EMT) markers in HG-induced HK-2 cells were quantified by Western blotting. miR-494-3p expression in HK-2 cells was detected by reverse-transcription quantitative polymerase chain reaction. The binding relation between miR-494-3p and the messenger RNA suppressor of cytokine signaling 6 (SOCS6) was detected by luciferase reporter assays. RESULTS: HG reduced cell viability and enhanced cell apoptosis in a time- or concentration-dependent manner. Additionally, HG induced collagen accumulation and triggered the EMT process. miR-494-3p was upregulated in HG-treated HK-2 cells. miR-494-3p inhibition alleviated HG-induced cell dysfunction. Mechanistically, miR-494-3p bound with SOCS6 and negatively regulated SOCS6 expression. Moreover, silencing SOCS6 rescued the suppressive effect of miR-499-5p inhibition on HG-induced cell dysfunction. CONCLUSION: miR-494-3p aggravates renal fibrosis, EMT process, and cell apoptosis by targeting SOCS6, suggesting that the miR-494-3p/SOCS6 axis may become a potential strategy for the treatment of diabetic nephropathy.


Subject(s)
Diabetic Nephropathies , MicroRNAs/metabolism , Suppressor of Cytokine Signaling Proteins/metabolism , Cell Line , Diabetic Nephropathies/pathology , Epithelial Cells/pathology , Fibrosis , Glucose/metabolism , Glucose/pharmacology , Humans
15.
PLoS Pathog ; 15(6): e1007836, 2019 06.
Article in English | MEDLINE | ID: mdl-31242272

ABSTRACT

Dengue is the most widespread vector-borne viral disease caused by dengue virus (DENV) for which there are no safe, effective drugs approved for clinical use. Here, by using sequential antigen panning of a yeast antibody library derived from healthy donors against the DENV envelop protein domain III (DIII) combined with depletion by an entry defective DIII mutant, we identified a cross-reactive human monoclonal antibody (mAb), m366.6, which bound with high affinity to DENV DIII from all four DENV serotypes. Immunogenetic analysis indicated that m366.6 is a germline-like mAb with very few somatic mutations from the closest VH and Vλ germline genes. Importantly, we demonstrated that it potently neutralized DENV both in vitro and in the mouse models of DENV infection without detectable antibody-dependent enhancement (ADE) effect. The epitope of m366.6 was mapped to the highly conserved regions on DIII, which may guide the design of effective dengue vaccine immunogens. Furthermore, as the first germline-like mAb derived from a naïve antibody library that could neutralize all four DENV serotypes, the m366.6 can be a tool for exploring mechanisms of DENV infection, and is a promising therapeutic candidate.


Subject(s)
Antibodies, Monoclonal/immunology , Antibodies, Neutralizing/immunology , Antibodies, Viral/immunology , Dengue Virus/immunology , Epitopes/immunology , Viral Envelope Proteins/immunology , Animals , Cell Line , Cricetinae , Dengue/genetics , Dengue/immunology , Dengue Virus/genetics , Epitopes/genetics , Humans , Viral Envelope Proteins/genetics
16.
Inorg Chem ; 60(4): 2542-2552, 2021 Feb 15.
Article in English | MEDLINE | ID: mdl-33481577

ABSTRACT

Uniform and well-dispersed SiO2:x%Tb3+@Lu2O3:y%Eu3+ core-shell spherical phosphors were synthesized via a solvothermal method followed by a subsequent calcination process. The structure, phase composition, and morphology of the samples were studied by X-ray diffraction (XRD), thermogravimetric analysis (TGA), Fourier transform infrared spectroscopy (FT-IR), field emission scanning electron microscopy (SEM), and transmission electron microscopy (TEM). The results showed that the Lu2O3:Eu3+ layer was evenly coated on the surface of SiO2:Tb3+ spheres and the shell thickness was about 45-65 nm. The PL spectra and fluorescence lifetimes of the samples were further studied. It was proved that the multicolor luminescence of the samples could be realized by changing the doping concentration ratio of Eu3+ or by changing the excitation wavelengths. Compared with SiO2@Lu2O3:3%Tb3+,6%Eu3+, SiO2:3%Tb3+@Lu2O3:6%Eu3+ showed stronger luminescence intensity, longer fluorescence lifetime, and higher energy transfer efficiency, which was attributed to the effective interfacial energy transfer, and the interfacial energy transfer mechanism from Tb3+ to Eu3+ was a dipole-dipole interaction mechanism. The XPS results indicated that the sample contained a high content of Si-O-Lu bonds, which proved that there was a strong interaction between the SiO2 core and the Lu2O3 shell, making the interfacial energy transfer possible. These results provided a new idea for luminescence enhancement and multicolor luminescence.

17.
Environ Sci Technol ; 55(3): 2006-2015, 2021 02 02.
Article in English | MEDLINE | ID: mdl-33434000

ABSTRACT

Previous studies demonstrated that methane can be used as an electron donor to microbially remove various oxidized contaminants in groundwater. Natural gas, which is more widely available and less expensive than purified methane, is potentially an alternative source of methane. However, natural gas commonly contains a considerable amount of ethane (C2H6) and propane (C3H8), in addition to methane. It is important that these gaseous alkanes are also utilized along with methane to avoid emissions. Here, we demonstrate that perchlorate (ClO4-), a frequently reported contaminant in groundwater, can be microbially reduced to chloride (Cl-) driven by C2H6 or C3H8 under oxygen-limiting conditions. Two independent membrane biofilm reactors (MBfRs) supplied with C2H6 and C3H8, respectively, were operated in parallel to biologically reduce ClO4-. The continuous ClO4- removal during long-term MBfR operation combined with the concurrent C2H6/C3H8 consumption and ClO4- reduction in batch tests confirms that ClO4- reduction was associated with C2H6 or C3H8 oxidation. Polyhydroxyalkanoates (PHAs) were synthesized in the presence of C2H6 or C3H8 and were subsequently utilized for supporting ClO4- bio-reduction in the absence of gaseous alkanes. Analysis by reverse transcription-quantitative polymerase chain reaction (RT-qPCR) showed that transcript abundance of bmoX (encoding alpha hydroxylase subunit of C2H6/C3H8 monooxygenase) was positively correlated to the consumption rates of C2H6/C3H8, while pcrA (encoding a catalytic subunit of perchlorate reductase) was positively correlated to the consumption of ClO4-. High-throughput sequencing targeting 16S rRNA, bmoX, and pcrA indicated that Mycobacterium was the dominant microorganism oxidizing C2H6/C3H8, while Dechloromonas may be the major perchlorate-reducing bacterium in the biofilms. These findings shed light on microbial ClO4- reduction driven by C2H6 and C3H8, facilitating the development of cost-effective strategies for ex situ groundwater remediation.


Subject(s)
Ethane , Perchlorates , Bioreactors , Oxidation-Reduction , Propane , RNA, Ribosomal, 16S/genetics
18.
Gynecol Endocrinol ; 37(12): 1072-1078, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34165386

ABSTRACT

OBJECTIVE: To assess the prevalence of anxiety and depression symptoms of different severity in women with polycystic ovary syndrome (PCOS) and explore the potential contributors related to these symptoms using a meta-analysis. MATERIALS AND METHODS: Databases were systemically searched for cross-sectional studies that evaluated the prevalence of anxiety and depression in women with PCOS published up to September 21 2019. Random effects model or fixed-effect model was used to analyze the data in meta-analysis. The pooled odds ratio (OR) and the pooled standardized mean difference (SMD) were performed to estimate the potential factors related to these symptoms. RESULT: A total of 24 cross-sectional studies were included. All studies assessed depression (2316 women with PCOS). Moreover, 16 studies assessed anxiety (1698 women with PCOS), and 6 studies assessed anxiety with depression (736 women with PCOS). The analysis revealed an increase in pool prevalence of depression (42%, 95%CI: 33-52%) and anxiety (37%, 95%CI: 14-60%) among the participants with PCOS, while the pooled prevalence of depression and concurrent anxiety was 28% (95%CI: 1.7-54.2%). Besides, the pooled prevalence of mild symptoms was higher than other levels (depression: 27.5%, 95%CI: 19-36%; anxiety: 35%, 95%CI: 0.8-70.8%). Obese women with PCOS had higher odds of depression (2.098, 95% CI: 1.411-3.119, I2=0.00%, p > .05). CONCLUSIONS: Our meta-analysis confirmed that women with PCOS had a high prevalence of anxiety and depression of different severity, with mild symptoms being more common. Moreover, obesity may increase the risk of depression symptoms, while potential contributors and mechanisms affecting these symptoms, such as hirsutism, infertility, insulin resistance (IR), and total testosterone in women with PCOS, need to be further investigated.


Subject(s)
Anxiety/epidemiology , Depression/epidemiology , Polycystic Ovary Syndrome/psychology , Anxiety/etiology , Cross-Sectional Studies , Depression/etiology , Female , Humans , Polycystic Ovary Syndrome/complications , Prevalence
19.
Mikrochim Acta ; 188(12): 407, 2021 11 04.
Article in English | MEDLINE | ID: mdl-34735602

ABSTRACT

A dual-mode DNA sensor was constructed to detect nucleic acid sensitively and selectively. Based on dendritic porous silica nanoparticles (DPSNs) and hybridization chain reaction (HCR) amplification strategy, the fabricated DNA sensor showed good sensitivity with low detection limits down to 2.18 pM and 4.02 pM by fluorescence (excited at 488 nm and emitted at 508 nm) and personal glucose meter (PGM) assays, respectively. This dual-mode detection of DNA offered superior reliability and accuracy and could meet the requirements of different testing environments, including laboratory confirmation and portable detection. Moreover, the impact of nanoparticles morphology on detection performance was also discussed. Due to the center-radial pores, DPSNs had high curvature morphology, which improved the coverage capacity, footprint, and deflection angle of probes. This work fabricated a dual-mode DNA sensor and revealed the relationship between morphology and detection performance, which brought new insights in novel biosensor development.


Subject(s)
Biosensing Techniques , DNA/chemistry , Fluorometry/methods , Nanoparticles/chemistry , Silicon Dioxide , Humans , Porosity , Surface Properties
20.
Eur J Neurosci ; 52(1): 2694-2704, 2020 07.
Article in English | MEDLINE | ID: mdl-31471985

ABSTRACT

Single-housed stress elicits a range of social isolation-related behavioral and neurobiological abnormalities. To investigate single housing-induced behavioral changes and sex differences on stress outcomes, we examined single-housed stress-induced learning and memory impairment, depression-like behaviors, neuroplasticity abnormalities and underlying mechanism. The results showed that male and female mice socially isolated for 8 weeks had significantly decreased memory acquisition, as demonstrated in the learning curve of the Morris water maze task. Memory consolidation and retrieval were also decreased in both the single-housed male and female mice. These findings were corroborated further by the two classical animal models, Y-maze and novel object recognition tests, as demonstrated by reduced spontaneous alternation and recognition index in both sexes of single-housed mice. Subsequent studies suggested that single-housed male mice exhibited increased immobility time in both the forced swim and tail suspension tests, while the female mice only exhibited increased immobility time in the tail suspension test. Moreover, single-housed stress significantly decreased the apical and basal branch points, dendritic length, and spine density in the CA1 of hippocampal neurons in both male and female mice. These effects were consistent with decreased neuroplasticity and neuroprotective-related molecules such as synaptophysin, PSD95, PKA, pCREB and BDNF expression. These findings suggest that loss of neuronal remodeling and neuroprotective mechanisms due to single housing are involved in behavioral changes in both male and female mice. The results provide further evidence that neuroplasticity-related signaling plays a crucial role in isolation-induced effects on neuropsychiatric behavioral deficits in both sexes.


Subject(s)
Cognitive Dysfunction , Depression , Animals , Behavior, Animal , Cognitive Dysfunction/etiology , Disease Models, Animal , Female , Hippocampus , Housing , Male , Maze Learning , Mice , Neuronal Plasticity
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