Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 1.145
Filtrar
1.
J Ethnopharmacol ; 283: 114674, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34560214

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Huoxue Tongluo Qiwei Decoction is a classical herbal formula, which can improve the symptoms of erectile dysfunction (ED) patients and has a good therapeutic effect on patients with diabetic erectile dysfunction (DIED). The main function of Huoxue Tongluo Qiwei Decoction is to stimulate the blood circulation and dredge collaterals, remove blood stasis, and calm wind. RATIONALE: To further explore the mechanism of Huoxue Tongluo Qiwei Decoction in the treatment of DIED, related animal experiments were designed. MATERIALS AND METHODS: The chemical constituents of Huoxue Tongluo Qiwei Decoction were identified with the help of high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). A rat model was induced by streptozotocin (STZ) and screened by apomorphine (APO). Serum sE-selectin, lysyl oxidase-1 (LOX-1), malondialdehyde (MDA) and other markers of vascular endothelial injury and related indicators of oxidative stress were studied through enzyme-linked immunosorbent assay (ELISA). The endothelial cells and ultrastructure of the corpus cavernosum were examined by electron microscopy and HE staining. The expression of protein and mRNA was detected by western blotting (WB) and real-time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The results of the study revealed that the sE-selectin, LOX-1, intercellular adhesion molecule-1 (sICAM-1), endothelial microparticles (EMPs), P-selectin (CD62P), and MDA levels in the serum of group M rats were considerably higher than rats of group K, while the superoxide dismutase (SOD) level showed a significant decrease. In addition, the PKC pathway was activated, and the expression of related proteins and mRNA was increased. After 8 weeks of intervention with Huoxue Tongluo Qiwei Decoction and LY333531, serum level of sE-selectin, LOX-1, sICAM-1, EMPs, CD62P and MDA in L, D and G groups were remarkably lower than group M while SOD level increased significantly, protein kinase C (PKC) pathway was inhibited with the improved erectile function of rats. CONCLUSION: Huoxue Tongluo Qiwei Decoction can inhibit the expression of protein and mRNA of the PKCß signaling pathway related molecules in DIED rats to cure the injury of vascular endothelial, enhance antioxidant capacity, and prevent the activation of platelet, thus improving erectile function in rats with DIED.

2.
Mol Ther Nucleic Acids ; 26: 773-786, 2021 Dec 03.
Artigo em Inglês | MEDLINE | ID: mdl-34729247

RESUMO

Circular RNAs (circRNAs) play important roles in carcinogenesis. Here, we investigated the mechanisms and clinical significance of circ-NOL10, a highly repressed circRNA in breast cancer. Subsequently, we also identified RNA-binding proteins (RBPs) that regulate circ-NOL10. Bioinformatics analysis was utilized to predict regulatory RBPs as well as circ-NOL10 downstream microRNAs (miRNAs) and mRNA targets. RNA immunoprecipitation, luciferase assay, fluorescence in situ hybridization, cell proliferation, wound healing, Matrigel invasion, cell apoptosis assays, and a xenograft model were used to investigate the function and mechanisms of circ-NOL10 in vitro and in vivo. The clinical value of circ-NOL10 was evaluated in a large cohort of breast cancer by quantitative real-time PCR. Circ-NOL10 is downregulated in breast cancer and associated with aggressive characteristics and shorter survival time. Upregulation of circ-NOL10 promotes apoptosis, decreases proliferation, and inhibits invasion and migration. Furthermore, circ-NOL10 binds multiple miRNAs to alleviate carcinogenesis by regulating PDCD4. CASC3 and metadherin (MTDH) can bind directly to circ-NOL10 with characterized motifs. Accordingly, ectopic expression or depletion of CASC3 or MTDH leads to circ-NOL10 expression changes, suggesting that these two RBPs modulate circ-NOL10 in cancer cells. circ-NOL10 is a novel biomarker for diagnosis and prognosis in breast cancer. These results highlight the importance of therapeutic targeting of the RBP-noncoding RNA (ncRNA) regulation network.

3.
Ophthalmol Ther ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34822140

RESUMO

INTRODUCTION: Meibomian gland dysfunction (MGD) is a common eye condition that causes excessive evaporation of tears by changing the tear film composition. Current treatments often fail to produce satisfactory results, which is mostly due to poor patient adherence. This study aimed to evaluate the effectiveness and safety of the MiBoFlo Thermoflo® on both subjective symptoms and objective signs in Chinese patients with MGD. METHODS: This prospective, randomized, controlled clinical trial included 108 eyes of 54 patients with MGD who were recruited in Beijing Tongren Hospital and randomized 1:1 to MiBoFlo (n = 54 eyes) or LipiFlow® (n = 54 eyes) treatment group. In the MiBoFlo group, patients received three 10-min treatments, each spaced 2 weeks apart, and the treatment was followed by eyelid compression each time. Patients in the LipiFlow group received a single 12-min treatment. The primary parameters measured included changes in Ocular Surface Disease Index (OSDI) score, Meibomian Glands Yielding Liquid Secretion (MGYLS) score, and Meibomian Glands Secretion (MGS) score from baseline to 2 months. The secondary parameters included tear meniscus height (TMH), non-invasive keratograph break-up time (NIKBUT), corneal fluorescein staining (CFS), and meibomian glands (MG) loss from baseline to 2 months. Safety parameters include visual acuity (VA), intraocular pressure (IOP), anterior segment, and facial skin. RESULTS: The OSDI, MGYLS, and MGS scores all improved from baseline to 1 month in both MiBoFlo and LipiFlow groups, and these improvements were maintained at 2 months. CFS score, NIKBUT, and MG loss showed no significant change in both groups. CONCLUSION: As a portable and comfortable device, MiBoFlo can improve the treatment of MGD and achieve a sustained improvement in both symptoms and meibomian gland function lasting at least 2 months.

4.
J Clin Pharm Ther ; 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34743357

RESUMO

WHAT IS KNOWN AND OBJECTIVE: Although several clinical trials have compared the clinical efficacy of clomiphene citrate (CC) combined with metformin (MET) in the treatment of women with polycystic ovary syndrome (PCOS), the results are controversial. Therefore, this study was designed to conduct a pooled analysis to evaluate the efficacy of CC combined with MET versus CC in these patients. METHODS: Computerized searches of the PubMed, Web of Science, Embase and Cochrane Library databases were conducted to identify eligible randomized controlled trials (RCTs) from the data obtained up to June 2021. The Cochrane Collaboration risk of bias tool was used to assess the risk of bias in individual RCTs, and RevMan 5.4 was used for data statistical analysis. RESULTS AND DISCUSSION: A total of 13 RCTs were included in the meta-analysis. These studies involved 1,353 patients, 707 of these were in the combination group and 646 in the monotherapy group. The results indicated a higher clinical pregnancy rate (risk ratio [RR] 1.28, 95% confidence interval [CI] 1.06-1.54, p = 0.01) in the combined group compared to the monotherapy group. However, no significant differences were observed in the ovulation rate (RR 1.13, 95% CI 0.98-1.30, p = 0.10), live birth rate (RR 1.13, 95% CI 0.89-1.42, p = 0.32), multiple pregnancy rate (RR 0.58, 95% CI 0.19-1.73, p = 0.33) and abortion rate (RR 1.26, 95% CI 0.86-1.84, p = 0.23) between the two groups. WHAT IS NEW AND CONCLUSION: CC combined with MET has an advantage in improving the clinical pregnancy rate compared to CC alone; however, there is no significant difference in the rate of ovulation. For better management of PCOS, a high-quality RCT is needed to demonstrate the safety of the combination.

5.
Anal Methods ; 13(45): 5450-5457, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34755722

RESUMO

In this paper, a novel type of zeolitic imidazolate framework-8 (ZIF-8) polyhedron/multi-walled carbon nanotube (MWCNT) modified electrode was successfully prepared for effective on-site detection of rutin. The morphology and microstructure of the ZIF-8/MWCNT nanocomposite were characterized using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray photoelectron spectroscopy (XPS) and X-ray diffraction (XRD). The electrochemical performance of the ZIF-8/MWCNT based electrode for the determination of rutin was studied by cyclic voltammetry (CV) and differential pulse stripping voltammetry (DPV). The as-prepared sensor illustrates better electrocatalytic activity and lower background current than the MWCNT modified electrode for the oxidation of rutin. Besides, the ZIF-8/MWCNTs sensor offers a remarkable linear response for rutin concentrations from 0.1 to 15 µM. The detection limit (LOD) was calculated to be 0.26 nM (S/N = 3). Also, the ZIF-8/MWCNT electrode showed high anti-interference ability towards common interfering species. More importantly, the fabricated electrode was quickly evaluated for determination of rutin in medicine tablets with satisfactory recoveries and the obtained results successfully achieved good consistency with the data from high performance liquid chromatography (HPLC). Finally, the method shows an enhanced electrocatalytic property and sensitivity for the analysis of rutin, which may provide an economical and promising electrochemical sensor for practical on-site detection of rutin.

6.
China CDC Wkly ; 3(17): 360-365, 2021 Apr 23.
Artigo em Inglês | MEDLINE | ID: mdl-34594884
7.
Macromol Rapid Commun ; : e2100497, 2021 Oct 04.
Artigo em Inglês | MEDLINE | ID: mdl-34608701

RESUMO

Porous materials have attracted significant attention because of their rising applications in many fields. Cyclodextrins (CDs) are suitable building units in the fabrication of porous materials owing to their intrinsic nanoporous structure, easy modification, and biocompatibility, which may result in the formation of CD-based organic frameworks (including cyclodextrin metal-organic frameworks (CD-MOFs) and cyclodextrin covalent organic frameworks (CD-COFs)), and CD-based polymer hybrid porous materials. This review focuses on the recent progress in the fabrication and applications of CD-based porous materials with novel structures and functionalities.

8.
Sci Rep ; 11(1): 19752, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-34611227

RESUMO

Although metabolic syndrome (MetS) is linked to an elevated risk of cardiovascular disease (CVD), the cardiac-specific risk mechanism is unknown. Obesity, hypertension, and diabetes (all MetS components) are the most common form of CVD and represent risk factors for worse COVID-19 outcomes compared to their non MetS peers. Here, we use obese Yorkshire pigs as a highly relevant animal model of human MetS, where pigs develop the hallmarks of human MetS and reproducibly mimics the myocardial pathophysiology in patients. Myocardium-specific mass spectroscopy-derived metabolomics, proteomics, and transcriptomics enabled the identity and quality of proteins and metabolites to be investigated in the myocardium to greater depth. Myocardium-specific deregulation of pro-inflammatory markers, propensity for arterial thrombosis, and platelet aggregation was revealed by computational analysis of differentially enriched pathways between MetS and control animals. While key components of the complement pathway and the immune response to viruses are under expressed, key N6-methyladenosin RNA methylation enzymes are largely overexpressed in MetS. Blood tests do not capture the entirety of metabolic changes that the myocardium undergoes, making this analysis of greater value than blood component analysis alone. Our findings create data associations to further characterize the MetS myocardium and disease vulnerability, emphasize the need for a multimodal therapeutic approach, and suggests a mechanism for observed worse outcomes in MetS patients with COVID-19 comorbidity.


Assuntos
COVID-19/patologia , Suscetibilidade a Doenças , Síndrome Metabólica/patologia , Animais , Fatores de Coagulação Sanguínea/genética , Fatores de Coagulação Sanguínea/metabolismo , COVID-19/complicações , COVID-19/virologia , Ciclo-Oxigenase 2/genética , Ciclo-Oxigenase 2/metabolismo , Dieta Hiperlipídica/veterinária , Modelos Animais de Doenças , Humanos , Imunidade Inata/genética , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Metiltransferases/genética , Metiltransferases/metabolismo , Miocárdio/metabolismo , Estresse Oxidativo/genética , Agregação Plaquetária , Receptores Purinérgicos P2Y1/genética , Receptores Purinérgicos P2Y1/metabolismo , Sistema Renina-Angiotensina , Fatores de Risco , SARS-CoV-2/isolamento & purificação , Suínos , Ativador de Plasminogênio Tipo Uroquinase/genética , Ativador de Plasminogênio Tipo Uroquinase/metabolismo
10.
J Card Surg ; 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34713498

RESUMO

BACKGROUND: Whether perioperative glycemic control is associated with neurocognitive decline (NCD) after cardiac surgery was examined. METHODS: Thirty patients undergoing cardiac surgery utilizing cardiopulmonary bypass (CPB) were screened for NCD preoperatively and on postoperative day 4 (POD4). Indices of glucose control were examined. Serum cytokine levels were measured and human transcriptome analysis was performed on blood samples. Neurocognitive data are presented as a change from baseline to POD4 in a score standardized with respect to age and gender. RESULTS: A decline in neurocognitive function was identified in 73% (22/30) of patients on POD4. There was no difference in neurocognitive function between patients with elevated HbA1c levels preoperatively (p = .973) or elevated fasting blood glucose levels the morning of surgery (>126 mg/dl, p = .910), or a higher maximum blood glucose levels during CPB (>180 mg/dl, p = .252), or higher average glucose levels during CPB (>160 mg/dl, p = .639). Patients with postoperative leukocytosis (WBC ≥ 10.5) had more NCD when compared to their baseline function (p = .03). Patients with elevated IL-8 levels at 6 h postoperatively had a significant decline in NCD at POD4 (p = .04). Human transcriptome analysis demonstrated unique and differential patterns of gene expression in patients depending on the presence of DM and NCD. CONCLUSIONS: Perioperative glycemic control does not have an effect on NCD soon after cardiac surgery. The profile of gene expression was altered in patients with NCD with or without diabetes.

11.
Gut Microbes ; 13(1): 1979883, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34632939

RESUMO

High alcohol-producing Klebsiella pneumoniae (HiAlc Kpn) in the gut microbiota had been demonstrated to be the causative agent of fatty liver disease (FLD). However, the catabolic pathways for alcohol production in vivo remain unclear. Here, we characterized the genome of HiAlc and medium alcohol-producing (MedAlc) Kpn and constructed an adh (an essential gene encoding alcohol dehydrogenase) knock-out HiAlc Kpn W14 strain (W14Δadh) using CRISPR-Cas9 system. Subsequently, we established the mouse model via gavage administration of HiAlc Kpn W14 and W14 Δadh strains, respectively. Proteome and metabolome analysis showed that 10 proteins and six major metabolites involved in the 2,3-butanediol fermentation pathway exhibited at least a three-fold change or greater during intestinal growth. Compared with HiAlc Kpn W14-fed mice, W14Δadh-fed mice with weak alcohol-producing ability did not show apparent pathological changes at 4 weeks, although some steatotic hepatocytes were observed at 12 weeks. Our data demonstrated that carbohydrate substances are catabolized to produce alcohol and 2,3-butanediol via the 2,3-butanediol fermentation pathway in HiAlc Kpn, which could be a promising clinical diagnostic marker. The production of high amounts of endogenous alcohol is responsible for the observed steatosis effects in hepatocytes in vivo.

13.
J Med Chem ; 64(20): 14983-14996, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34643383

RESUMO

RORγ is a dual-functional drug target, which involves not only induction of inflammation but also promotion of cancer immunity. The development of agonists of RORγ promoting Th17 cell differentiation could provide a novel mechanism of action (MOA) as an immune-activating anticancer agent. Herein, we describe new 2-(ortho-substituted benzyl)-indole derivatives as RORγ agonists by scaffold hopping based on clinical RORγ antagonist VTP-43742. Interestingly, subtle structural differences of the compounds led to the opposite biological MOA. After rational optimization for structure-activity relationship and pharmacokinetic profile, we identified a potent RORγ agonist compound 17 that was able to induce the production of IL-17 and IFNγ in tumor tissues and elicit antitumor efficacy in MC38 syngeneic mouse colorectal tumor model. This is the first comprehensive work to demonstrate the in vivo antitumor efficacy of an RORγ agonist.

14.
Comput Intell Neurosci ; 2021: 5538791, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34545281

RESUMO

Sentiment analysis is an essential process which is important to many natural language applications. In this paper, we apply two models for Arabic sentiment analysis to the ASTD and ATDFS datasets, in both 2-class and multiclass forms. Model MC1 is a 2-layer CNN with global average pooling, followed by a dense layer. MC2 is a 2-layer CNN with max pooling, followed by a BiGRU and a dense layer. On the difficult ASTD 4-class task, we achieve 73.17%, compared to 65.58% reported by Attia et al., 2018. For the easier 2-class task, we achieve 90.06% with MC1 compared to 85.58% reported by Kwaik et al., 2019. We carry out experiments on various data splits, to match those used by other researchers. We also pay close attention to Arabic preprocessing and include novel steps not reported in other works. In an ablation study, we investigate the effect of two steps in particular, the processing of emoticons and the use of a custom stoplist. On the 4-class task, these can make a difference of up to 4.27% and 5.48%, respectively. On the 2-class task, the maximum improvements are 2.95% and 3.87%.


Assuntos
Idioma
15.
J Gastrointest Oncol ; 12(4): 1338-1350, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532092

RESUMO

Background: The albumin-to-alkaline phosphatase ratio (AAPR) is an innovative prognostic index for various cancer patients, the clinical significance of the AAPR in patients with GC is unknown. Methods: We retrospectively reviewed 227 resectable GC patients in our center. The Kaplan-Meier method and the Cox proportional hazards model were used to analyze the disease-free survival (DFS) and overall survival (OS). The Likelihood Ratio Test (LRT) and Akaike information criterion (AIC) were used to compare the prognostic abilities of the TNM and AAPR-TNM staging systems in DFS and OS prediction. Results: The AAPR was significantly decreased in GC patients, and the optimal cut-off value for resectable and benign gastric disease was 0.437 as determined by the receiver operating characteristic (ROC) curve. The correlation analysis revealed that decreased AAPR in GC was associated with T stage (P=0.004) and TNM stage (P=0.013). Decreased preoperative AAPR correlated with both unfavorable disease-free survival (DFS) and overall survival (OS). Cox regression analysis showed that the TNM stage (DFS: P=0.001, OS: P=0.002) and differential levels of AAPR (DFS: P<0.001, OS: P<0.001) were independent risk factors of DFS and OS. ROC analysis showed that the AAPR-TNM system was more superior than the TNM staging system for DFS (z=1.91, P=0.028) and OS (z=1.937, P=0.026) prediction. The likelihood ratio test (LRT) analysis indicated that the AAPR-TNM system had a significantly larger χ2 for both DFS (35.58 vs. 34.51, P<0.001) and OS (32.92 vs. 30.07, P<0.001), and a lower Akaike information criterion (AIC) value both for DFS (1,032 vs. 1,065, P<0.001) and OS (869 vs. 898, P<0.001) compared to the TNM system. Conclusions: The AAPR level significantly decreased in patients with GC, and impacted the prognosis of patients.

16.
Onco Targets Ther ; 14: 4561-4574, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34466002

RESUMO

Introduction: CD73 and adenosine support growth-promoting neovascularization, metastasis, and survival in cells, and promote anti-PD-1 mAb therapy-induced immune escape. Consequently, developing a CD73 inhibitor as monotherapy and a potential beneficial combination partner with immune-checkpoint inhibitors needs investigation. Methods: CD73 inhibitors were evaluated in vitro with soluble and membrane-bound CD73 enzymes, as well as its PD biomarker responses in human peripheral blood mononuclear cells (PBMC) by flow cytometry and ELISA. The binding modes of the molecules were analyzed via molecular modeling. The anti-tumor activity and synergistic effect of SHR170008 in combination with anti-PD-1 mAb were evaluated in a syngeneic mouse breast cancer model. Results: SHR170008 was discovered during the initial structural modifications on the link between the ribose and the α-phosphate of AMPCP, which significantly improved the stability of the compound confirmed by the metabolite identification study. Further modifications on the adenine base of AMPCP improved the potency due to forming stronger interactions with CD73 protein. It exhibited potent inhibitory activities on soluble and endogenous membrane-bound CD73 enzymes, and induced IFNγ production, reversed AMP-suppressed CD25+ and CD8+/CD25+ expression, and enhanced granzyme B production on CD8+ T cells in human PBMC. SHR170008 showed dose-dependent anti-tumor efficacy with suppression of adenosine in the tumors in EMT6 mouse breast tumor model. The increase of adenosine in tumor tissue by anti-PD-1 mAb alone was suppressed by SHR170008 in the combination groups. Simultaneous inhibition of CD73 and PD-1 neutralization synergistically enhanced antitumor immunity and biomarkers in response, and exposures of SHR170008 were correlated with the efficacy readouts. Conclusion: Our findings suggest that CD73 may serve as an immune checkpoint by generating adenosine, which suppresses the antitumor activity of anti-PD-1 mAb, and inhibition of CD73 may be a potential beneficial combination partner with immune-checkpoint inhibitors to improve their therapeutic outcomes in general.

17.
Bioorg Med Chem ; 47: 116350, 2021 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-34536651

RESUMO

The antiapoptotic protein B-cell lymphoma 2 (Bcl-2), overexpressed in many tumor cells, is an attractive target for potential small molecule anticancer drug discovery. Herein, a series of novel derivatives with acyl sulfonamide skeleton was designed, synthesized, and evaluated as Bcl-2 inhibitors by means of bioisosteric replacement. Among them, compound 24g demonstrated equal efficient inhibition activity against RS4;11 cell line compared to positive control ABT-199. Moreover, it showed improved selectivity for Bcl-2/Bcl-xL inhibitory effects, the result of which was consistent with platelet toxicity studies. In vitro and in vivo pharmacokinetic properties of compound 24g had a significantly improved profiles. Taken together, those results suggested it as a promising candidate for development of novel therapeutics targeting Bcl-2 in cancer.

18.
Front Cell Infect Microbiol ; 11: 673194, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34568082

RESUMO

Background: Sulfadoxine-pyrimethamine (SP) is recommended for intermittent preventive treatment in Africa against Plasmodium falciparum infection. However, increasing SP resistance (SPR) of P. falciparum affects the therapeutic efficacy of SP, and pfdhfr (encoding dihydrofolate reductase) and pfdhps (encoding dihydropteroate synthase) genes are widely used as molecular markers for SPR surveillance. In the present study, we analyzed single nucleotide polymorphisms (SNPs) of pfdhfr and pfdhps in P. falciparum isolated from infected Chinese migrant workers returning from Africa. Methods: In total, 159 blood samples from P. falciparum-infected workers who had returned from Africa to Anhui, Shangdong, and Guangxi provinces were successfully detected and analyzed from 2017 to 2019. The SNPs in pfdhfr and pfdhps were analyzed using nested PCR. The genotypes and linkage disequilibrium (LD) were analyzed using Haploview. Results: High frequencies of the Asn51Ile (N51I), Cys59Arg(C59R), and Ser108Asn(S108N) mutant alleles were observed, with mutation frequencies of 97.60, 87.43, and 97.01% in pfdhfr, respectively. A triple mutation (IRN) in pfdhfr was the most prevalent haplotype (86.83%). Six point mutations were detected in pfdhps DNA fragment, Ile431Val (I431V), Ser436Ala (S436A), Ala437Gly (A437G), Lys540Glu(K540E), Ala581Gly(A581G), Ala613Ser(A613S). The pfdhps K540E (27.67%) was the most predominant allele, followed by S436A (27.04%), and a single mutant haplotype (SGKAA; 62.66%) was predominant in pfdhps. In total, 5 haplotypes of the pfdhfr gene and 13 haplotypes of the pfdhps gene were identified. A total of 130 isolates with 12 unique haplotypes were found in the pfdhfr-pfdhps combined haplotypes, most of them (n = 85, 65.38%) carried quadruple allele combinations (CIRNI-SGKAA). Conclusion: A high prevalence of point mutations in the pfdhfr and pfdhps genes of P. falciparum isolates was detected among Chinese migrant workers returning from Africa. Therefore, continuous in vitro molecular monitoring of Sulfadoxine-Pyrimethemine combined in vivo therapeutic monitoring of artemisinin combination therapy (ACT) efficacy and additional control efforts among migrant workers are urgently needed.


Assuntos
Antimaláricos , Malária Falciparum , África , Antimaláricos/farmacologia , China , Estudos Transversais , Combinação de Medicamentos , Resistência a Medicamentos/genética , Humanos , Mutação , Plasmodium falciparum/genética , Proteínas de Protozoários/genética , Pirimetamina , Sulfadoxina , Tetra-Hidrofolato Desidrogenase/genética
19.
PLoS Negl Trop Dis ; 15(9): e0009730, 2021 09.
Artigo em Inglês | MEDLINE | ID: mdl-34492012

RESUMO

In recent years, the human gut microbiome has been recognised to play a pivotal role in the health of the host. Intestinal homeostasis relies on this intricate and complex relationship between the gut microbiota and the human host. While much effort and attention has been placed on the characterization of the organisms that inhabit the gut microbiome, the complex molecular cross-talk between the microbiota could also exert an effect on gastrointestinal conditions. Blastocystis is a single-cell eukaryotic parasite of emerging interest, as its beneficial or pathogenic role in the microbiota has been a subject of contention even to-date. In this study, we assessed the function of the Blastocystis tryptophanase gene (BhTnaA), which was acquired by horizontal gene transfer and likely to be of bacterial origin within Blastocystis. Bioinformatic analysis and phylogenetic reconstruction revealed distinct divergence of BhTnaA versus known bacterial homologs. Despite sharing high homology with the E. coli tryptophanase gene, we show that Blastocystis does not readily convert tryptophan into indole. Instead, BhTnaA preferentially catalyzes the conversion of indole to tryptophan. We also show a direct link between E. coli and Blastocystis tryptophan metabolism: In the presence of E. coli, Blastocystis ST7 is less able to metabolise indole to tryptophan. This study examines the potential for functional variation in horizontally-acquired genes relative to their canonical counterparts, and identifies Blastocystis as a possible producer of tryptophan within the gut.

20.
Sci Rep ; 11(1): 17401, 2021 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-34465795

RESUMO

Cataracts, named for pathological light scattering in the lens, are known to be associated with increased large protein aggregates, disrupted protein phase separation, and/or osmotic imbalances in lens cells. We have applied synchrotron phase contrast X-ray micro-computed tomography to directly examine an age-related nuclear cataract model in Cx46 knockout (Cx46KO) mice. High-resolution 3D X-ray tomographic images reveal amorphous spots and strip-like dense matter precipitates in lens cores of all examined Cx46KO mice at different ages. The precipitates are predominantly accumulated in the anterior suture regions of lens cores, and they become longer and dense as mice age. Alizarin red staining data confirms the presence of calcium precipitates in lens cores of all Cx46KO mice. This study indicates that the spatial and temporal calcium precipitation is an age-related event associated with age-related nuclear cataract formation in Cx46KO mice, and further suggests that the loss of Cx46 promotes calcium precipitates in the lens core, which is a new mechanism that likely contributes to the pathological light scattering in this age-related cataract model.


Assuntos
Cálcio/metabolismo , Catarata/metabolismo , Animais , Catarata/patologia , Cristalino/metabolismo , Camundongos , Camundongos Knockout , Microtomografia por Raio-X
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...