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1.
Talanta ; 221: 121668, 2021 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-33076174

RESUMO

Rapid and sensitive diagnosis of bacterial infections at early stage is of great significance for food safety monitoring as well as clinical treatment. Herein, we construct a surface-enhanced Raman scattering (SERS) nanoprobe based on M13 phages for the selective detection and inactivation of Staphylococcus aureus (S. aureus). M13 phage with specific S. aureus-binding heptapeptide displayed on the N-terminal of pIII protein is selected from phage display peptide library. The S. aureus-specific SERS probe is thus constructed by in situ growth of gold nanoparticles (AuNPs) on M13 phage surface, followed by modification with 5,5-dithiobis-(2-nitrobenzoic acid) (DTNB) as SERS active molecule. Upon the addition of this SERS probe, M13 phage selectively binds with S. aureus to induce anchoring of AuNPs on S. aureus surface, and the SERS probe-labeled S. aureus cells are collected by centrifugation for SERS detection. For the quantification of S. aureus, a linear range of 10-106 cfu mL-1 is achieved in aqueous medium. It is further demonstrated by spiking recovery in soft drinks. Furthermore, this SERS probe exhibits bactericidal capabilities towards S. aureus, which shows promising potential to serve as a multifunctional platform for simultaneous detection and inactivation of S. aureus.

2.
Theranostics ; 10(24): 11339-11358, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33042286

RESUMO

Background: TSTA3 gene encodes an enzyme responsible for synthesis of GDP-L-fucose as the only donor in fucosylation. This study was designed to explore clinical value, function and underlying mechanism of TSTA3 in the development of esophageal squamous cell carcinoma (ESCC). Methods: Whole genomic sequencing data from 663 ESCC patients and RNA sequencing data from 155 ESCC patients were used to analyze the copy number variation and mRNA expression of TSTA3 respectively. Immunohistochemistry based or not based on the tissue microarrays was used to detect its protein expression. Transwell assay and in vivo metastasis assay were used to study the effect of TSTA3 on invasion and metastasis of ESCC. Immunofluorescence was used to analyze fucosylation level. N-glycoproteomics and proteomics analysis, Lens Culinaris Agglutinin (LCA) and Ulex Europaeus Agglutinin I (UEA-I) affinity chromatography, immunoprecipitation, glycosyltransferase activity kit and rescue assay were used to explore the mechanism of TSTA3. Results: TSTA3 was frequently amplified and overexpressed in ESCC. TSTA3 amplification and protein overexpression were significantly associated with malignant progression and poor prognosis of ESCC patients. TSTA3 knockdown significantly suppressed ESCC cells invasion and tumor dissemination by decreasing fucosylation level. Conversely, exogenous overexpression of TSTA3 led to increased invasion and tumor metastasis in vitro and in vivo by increasing fucosylation level. Moreover, core fucosylated LAMP2 and terminal fucosylated ERBB2 might be mediators of TSTA3-induced pro-invasion in ESCC and had a synergistic effect on the process. Peracetylated 2-F-Fuc, a fucosyltransferase activity inhibitor, reduced TSTA3 expression and fucosylation modification of LAMP2 and ERBB2, thereby inhibiting ESCC cell invasion. Conclusion: Our results indicate that TSTA3 may be a driver of ESCC metastasis through regulating fucosylation of LAMP2 and ERBB2. Fucosylation inhibitor may have prospect to suppress ESCC metastasis by blocking aberrant fucosylation.

3.
Clin Biochem ; 2020 Oct 17.
Artigo em Inglês | MEDLINE | ID: mdl-33080253

RESUMO

INTRODUCTION: Coronary artery disease (CAD) is an ischemic heart disease due to the narrowing of the coronary arteries resulting from atherosclerosis. Blood biomarkers have been well utilized for the diagnosis and prognosis of CAD. However, the value of biomarkers for evaluating coronary atherosclerosis remains to be clarified. This clinical investigation aimed to explore the potential value of biomarkers for evaluating the severity of coronary stenosis in CAD patients METHODS: The extent of coronary atherosclerosis was accessed by the angiography-based quantitative measurement Gensini score (GS). Blood levels of Brain natriuretic peptide, Copeptin (CPP), Phosphodiesterase 9A, and Pentraxin3 (PTX3) were measured in 56 patients divided into three levels as low GS (n=17), intermediate GS (n=19) and high GS (n=20) based on GS tertiles. RESULTS: we found that plasma concentrations of CPP and PTX3 were significantly elevated in patients with high GS compared with the low GS group. In addition, Pearson correlation analysis showed that CPP and PTX3 were positively correlated with the GS. Furthermore, Receiver operating characteristics analysis demonstrated that both CPP and PTX3 exhibited discriminative capacities for evaluating the extent of coronary stenosis. CONCLUSIONS: Laboratory tests of CPP and PTX3 via non-invasive means may provide novel information for risk stratification and disease management in CAD patients before invasive angiographic approaches. This study opens the door for enormous opportunities to explore new biomarkers with better efficiency, sensitivity and specificity as alternative/additional methods for evaluating the severity of coronary atherosclerosis in CAD patients in future research.

4.
Cell Death Discov ; 6: 99, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33083020

RESUMO

Long noncoding RNAs (LncRNAs) have been reported to play critical roles in gastric cancer, but true biomarkers remain unknown. In this study, we found a new lncRNA LINC00355 that was involved in malignant progression of gastric cancer (GC) and further revealed its role and mechanism. Differentially expressed lncRNAs were identified through bioinformatics, and qRT-PCR was used to validate the expression of LINC00355 in gastric cancer tissues and cells. The biological role of LINC00355 in GC was detected by gene overexpression and knockdown experiments. Subcellular fractionation, qRT-PCR, and FISH were performed to detect the subcellular localization. Co-IP and western blotting were used to study the ubiquitination-mediated regulation of P53 and the expression of the E3 ligases RAD18 and UBE3C. The results showed that LINC00355 was significantly increased in gastric cancer cell lines and patient tissues and closely correlated with late stages, distant metastasis, and poor prognosis of patients. High expression of LINC00355 promoted the proliferation and invasion of gastric cancer cells in vivo and in vitro. Mechanistic studies found that LINC00355 that mainly located in the nucleus, acting as a transcriptional activator, promoted transcription of RAD18 and UBE3C, which both bind to P53 and mediate the ubiquitination and degradation of P53. Furthermore, LINC00355 overexpression enhanced the ubiquitination process, and LINC00355 knockdown alleviated it. These results indicated that LINC00355 induces gastric cancer cell proliferation and invasion by promoting transcription of RAD18 and UBE3C, which mediates ubiquitination of P53 and thereby plays a critical role in survival and tumorigenicity of gastric cancer cells. LINC00355 may represent a new mechanism for GC progression and provide a potential marker for GC diagnosis and treatment.

5.
Surg Oncol ; 35: 426-427, 2020 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-33038848

RESUMO

INTRODUCTION: Digital intelligent technology represented by three-dimensional (3D) visualization technology and surgical navigation system may provide preoperative and intraoperative anatomical information more accurately than CT and MRI [1]. Besides, the fusion of 3D model with surgical visual field through surgical navigation system may also compensate for the defects of visual fields and tactile sense to some extent in laparoscopic liver surgery [2]. VIDEO: A 49-year-old male patient with a tumor mainly located at the left inner area of liver and oppressing the middle hepatic vein (MHV). We formulated preoperative planning by using the Medical Image 3D Visualization System (MI3DVS, software copyright No: 2008SR18798) [3]. It was acknowledged that the right hepatic vein (RHV) was strong enough to drain the right anterior hepatic sector. Ultimately, 3D laparoscopic extended left hepatectomy with resection of the MHV was selected as the optimal operation scheme for the patient due to the RHV would avoid hepatic venous congestion in segment V and VIII after resection of the MHV, and more liver parenchyma than left trisegmentectomy would be retained. The operation was performed under assistance of the Laparoscopic Hepatectomy Navigation System (LHNS, software copyright No. 2018SR840555) [4]. RESULTS: The total operation time was 180 min, estimated blood loss of 200 ml. The final histopathological diagnosis showed an 8*6*6-cm-sized hepatocellular carcinoma. And the patient was discharged on postoperative day 6 without any complications. CONCLUSION: Digital intelligent technology may be helpful to formulate preoperative planning and identify intraoperative important anatomical structures in 3D laparoscopic extended left hepatectomy with resection of the MHV.

6.
Mediators Inflamm ; 2020: 8191079, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061831

RESUMO

Disrupted immune response is an important feature of many neurodegenerative conditions, including sepsis-associated cognitive impairment. Accumulating evidence has demonstrated that immune memory occurs in microglia, which has a significant impact on pathological hallmarks of neurological diseases. However, it remains unclear whether immune memory can cause subsequent alterations in the brain immune response and affect neurobehavioral outcomes in sepsis survivors. In the present study, mice received daily intraperitoneal injection of low-dose lipopolysaccharide (LPS, 0.1 mg/kg) for three consecutive days to induce immune memory (immune tolerance) and then were subjected to sham operation or cecal ligation and puncture (CLP) 9 months later, followed by a battery of neurobehavioral and biochemical studies. Here, we showed that repeated low-dose LPS injection-induced immune memory protected mice from sepsis-induced cognitive and affective impairments, which were accompanied by significantly decreased brain proinflammatory cytokines and immune response. In conclusion, our study suggests that modulation of brain immune responses by repeated LPS injections confers neuroprotective effects by preventing overactivated immune response in response to subsequent septic insult.

7.
BMC Plant Biol ; 20(1): 469, 2020 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-33046012

RESUMO

BACKGROUND: Ecological environments shape plant architecture and alter the growing season, which provides the basis for wheat genetic improvement. Therefore, understanding the genetic basis of grain yield and yield-related traits in specific ecological environments is important. RESULTS: A structured panel of 96 elite wheat cultivars grown in the High-yield zone of Henan province in China was genotyped using an Illumina iSelect 90 K SNP assay. Selection pressure derived from ecological environments of mountain front and plain region provided the initial impetus for population divergence. This determined the dominant traits in two subpopulations (spike number and spike percentage were dominance in subpopulation 2:1; thousand-kernel weight, grain filling rate (GFR), maturity date (MD), and fertility period (FP) were dominance in subpopulation 2:2), which was also consistent with their inheritance from the donor parents. Genome wide association studies identified 107 significant SNPs for 12 yield-related traits and 10 regions were pleiotropic to multiple traits. Especially, GY was co-located with MD/FP, GFR and HD at QTL-ple5A, QTL-ple7A.1 and QTL-ple7B.1 region. Further selective sweep analysis revealled that regions under selection were around QTLs for these traits. Especially, grain yield (GY) is positively correlated with MD/FP and they were co-located at the VRN-1A locus. Besides, a selective sweep signal was detected at VRN-1B locus which was only significance to MD/FP. CONCLUSIONS: The results indicated that extensive differential in allele frequency driven by ecological selection has shaped plant architecture and growing season during yield improvement. The QTLs for yield and yield components detected in this study probably be selectively applied in molecular breeding.

8.
Sci Total Environ ; : 142675, 2020 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-33077208

RESUMO

There is limited knowledge about how microbiome develops along the geochemical and mineralogical change in onshore soils derived from continuous desiccation of lakes. In this study, geochemistry and mineralogy were studied in the Aral Sea onshore soils exposed in different periods (from the 1970s to 2018), followed by microbial analyses on the studied soils and the aboveground organs of dominant plants. The soils exhibited an increasing gradient of total soluble salts (TSS: 0.4-0.5 g/L to 71.3 g/L) and evaporite minerals (e.g., gypsum, halite) from the farshore to the nearshore. In the studied soils, microbial diversity decreased with increasing TSS, and microbial community dissimilarities among samples was positively correlated with the contents of gypsum and calcite minerals. Among the measured environmental variables, minerals contributed most to the observed microbial variation. In contrast, the endophytic microbial communities in the aboveground organs of dominant plants were not related to any of the measured variables, indicating that they differed from their soil counterparts with respect to their responses to geochemical and mineralogical variations in soils. In summary, these results help us understand the response of onshore soil microbiome to the decline of lake water caused by continuous desiccation.

9.
Carbohydr Polym ; 250: 116881, 2020 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-33049824

RESUMO

Three-dimensional (3D) printing, known as revolutionary and disruptive innovation in manufacturing technology, supports great opportunities to rapidly construct a wide range of tailored object geometries. Cellulose, hemicellulose, and lignin as the three most common natural polymers and main components of plant resources, possess great economical potential for bio-based products due to their attractive advantages. The integration of 3D printing technology involved with cellulose, hemicellulose and lignin as the major bio-based feedstock for high-performance 3D printed products has received great concern in the R&D areas. In this review, the aim is to shed light on a cutting-edge review on the most recent progress based on cellulose, hemicellulose and lignin, as well as their derivatives as multi-components of bio-feedstock for 3D printing, in which the applications, roles and functions of the plant-derived biomass for 3D printing are also highlighted. The challenges and perspectives for future work are provided, to underscore critical issues and opportunities.

10.
Microbiome ; 8(1): 145, 2020 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-33032658

RESUMO

BACKGROUND: Interest in the interplay between host genetics and the gut microbiome in complex human diseases is increasing, with prior evidence mainly being derived from animal models. In addition, the shared and distinct microbiome features among complex human diseases remain largely unclear. RESULTS: This analysis was based on a Chinese population with 1475 participants. We estimated the SNP-based heritability, which suggested that Desulfovibrionaceae and Odoribacter had significant heritability estimates (0.456 and 0.476, respectively). We performed a microbiome genome-wide association study to identify host genetic variants associated with the gut microbiome. We then conducted bidirectional Mendelian randomization analyses to examine the potential causal associations between the gut microbiome and complex human diseases. We found that Saccharibacteria could potentially decrease the concentration of serum creatinine and increase the estimated glomerular filtration rate. On the other hand, atrial fibrillation, chronic kidney disease and prostate cancer, as predicted by host genetics, had potential causal effects on the abundance of some specific gut microbiota. For example, atrial fibrillation increased the abundance of Burkholderiales and Alcaligenaceae and decreased the abundance of Lachnobacterium, Bacteroides coprophilus, Barnesiellaceae, an undefined genus in the family Veillonellaceae and Mitsuokella. Further disease-microbiome feature analysis suggested that systemic lupus erythematosus and chronic myeloid leukaemia shared common gut microbiome features. CONCLUSIONS: These results suggest that different complex human diseases share common and distinct gut microbiome features, which may help reshape our understanding of disease aetiology in humans. Video Abstract.

11.
Mol Med Rep ; 22(5): 3804-3812, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33000209

RESUMO

Glioma is a malignant brain cancer that exhibits high invasive ability and poor prognosis. MicroRNA (miR)­181d has been reported to be involved in the development of glioma. Therefore, the aim of the present study was to investigate whether miR­181d affected cellular progression by influencing the insulin like growth factor (IGF1)/PI3K/AKT axis. Western blot analysis was performed to analyze the expression levels of specific proteins, and a Cell Counting Kit­8 assay was used to assess the proliferative ability of cells. Cell cycle progression and cellular apoptosis were both measured using flow cytometry. The results indicated that miR­181d promoted cellular proliferation and cell cycle progression, while suppressing cellular apoptosis via the IGF1/PI3K/AKT axis. It was demonstrated that the IGF1 and PI3K/AKT inhibitors reversed these observed functions of miR­181d. Furthermore, miR­181d enhanced the growth of glioma xenografts in vivo, promoted cell cycle progression and suppressed cellular apoptosis within glioma xenograft tissues. Therefore, this newly identified miR­181d/IGF1/PI3K/AKT axis may provide novel insights into the pathogenesis of glioma.

12.
Eur J Med Chem ; : 112922, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33069436

RESUMO

Magnolol and honokiol are the two major active ingredients with similar structure and anticancer activity from traditional Chinese medicine Magnolia officinalis, and honokiol is now in a phase I clinical trial (CTR20170822) for advanced non-small cell lung cancer (NSCLC). In search of potent lead compounds with better activity, our previous study has demonstrated that magnolol derivative C2, 3-(4-aminopiperidin-1-yl)methyl magnolol, has better activity than honokiol. Here, based on the core of 3-(4-aminopiperidin-1-yl)methyl magnolol, we synthesized fifty-one magnolol derivatives. Among them, compound 30 exhibited the most potent antiproliferative activities on H460, HCC827, H1975 cell lines with the IC50 values of 0.63-0.93 µM, which were approximately 10- and 100-fold more potent than those of C2 and magnolol, respectively. Besides, oral administration of 30 and C2 on an H460 xenograft model also demonstrated that 30 has better activity than C2. Mechanism study revealed that 30 induced G0/G1 phase cell cycle arrest, apoptosis and autophagy in cancer cells. Moreover, blocking autophagy by the autophagic inhibitor enhanced the anticancer activity of 30in vitro and in vivo, suggesting autophagy played a cytoprotective role on 30-induced cancer cell death. Taken together, our study implied that compound 30 combined with autophagic inhibitor could be another choice for NSCLC treatment in further investigation.

13.
J Clin Neurosci ; 79: 251-256, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-33070906

RESUMO

This study is to investigate the presence of brain gray matter abnormalities in young onset essential tremor (ET) patients with arm tremor. Thirty ET patients together with 30 healthy volunteers were taken as candidates. Magnetic resonance imaging (MRI) was performed and voxel-based morphometry was used to compare gray matter density between the patients and volunteers. Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) rating scale was applied to assess tremor severity in the patients. Eventually Twenty-Seven ET patients and Twenty-Seven volunteers were enrolled in the study. Voxel-based morphometry showed significant expansion of the bilateral cerebellum, occipital fusiform cortices, right inferior temporal gyrus, and precentral lobes (P < 0.05, TFCE corrected). Decrease in gray matter was detected only in the left parietal lobe. Region of interest analysis showed volume enlargement in thalamus, midbrain, and precuneus (P < 0.05, TFCE corrected). Importantly, significant negative correlation was found between the lateralized index of cerebellum and the tremor score which might implicate that the altered rightward lateralization in the cerebellum is possibly a response of the tremor effects in ET patients. Cerebellar gray matter expansion in young onset ET patients with arm tremor might be the result of compensation towards decline of cerebellar function.

14.
Mikrochim Acta ; 187(11): 614, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33073313

RESUMO

A novel molecularly imprinted ratiometric fluorescent probe was fabricated by simple sol-gel polymerization for selective and sensitive assay of C-type natriuretic peptide (CNP) in biosamples. Both the nitrobenzoxadiazole (NBD) and carbon dots (CDs) were located on the surface of silica, used as the detection signal and reference signal, respectively. For the turn-on-based probe, the fluorescence intensity of NBD could be quantitatively enhanced by CNP based on the strategy of photo-induced electron transfer (PET), while the fluorescence of CDs remained unchanged. The obtained probe exhibited excellent recognition selectivity and fast kinetics to CNP templates, and also showed good stability. The linear range of CNP determination was 5-80 pg mL-1 with a low detection limit of 2.87 pg mL-1. Finally, the probe was successfully applied to determine CNP in human serum samples and attained high recoveries between 97.3 and 104% with precisions below 4.7%. The result indicates that the proposed method has promising potential for the assay of trace peptides in complex matrices. Schematic illustration for the formation and determination mechanism of the probe.

16.
Zootaxa ; 4861(1): zootaxa.4861.1.3, 2020 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-33055868

RESUMO

The Music Frog genus Nidirana was recently resurrected as a distinct genus and contains 14 species distributed in subtropical eastern and southeastern Asia. The species diversity of Nidirana is dramatically underestimated, and half of its species was described in the last five years. In this study, Nidirana occidentalis sp. nov., a new species of Music Frog from western Yunnan, China, is proposed based on morphological and molecular evidences. The new species was previously misidentified as N. pleuraden, but can be distinguished from the true N. pleuraden from eastern Yunnan, and all other congeners, by a combination of morphological characteristics, and significant divergence in the mitochondrial genes (≥ 5.1% in 16S and ≥ 8.9% in CO1). Nidirana occidentalis sp. nov. is assigned to the N. pleuraden group on the basis of morphological characters, but its phylogenetic placement remains unresolved due to weak branch support. Geographically, these two species are isolated by the Red River in Yunnan, supporting the hypothesis that the Red River is an important geographical barrier that drives speciation in flora and fauna. Nidirana occidentalis sp. nov. represents the second species of N. pleuraden group and the 15th species of the genus.

17.
Artigo em Inglês | MEDLINE | ID: mdl-32902900

RESUMO

Apyrase represents an important family of extracellular enzymes that catalyze the hydrolysis of high-energy phosphate bonds (HEPBs) in ATP and ADP, thereby modulating many physiological processes and driving life activities. Here, we report an unexpected discovery that cerium-based metal-organic frameworks (Ce-MOFs) of UiO-66(Ce) possess intrinsic apyrase-like activity for the intervention of ATP/ADP-related physiological processes. The abundant Ce(III)/Ce(IV) couple sites of Ce-MOFs endow them with the ability to selectively catalyse the hydrolysis of HEPBs of ATP and ADP under physiological condition. Compared to natural enzymes, they could resist to extreme pH and temperature, and present a broad range of working conditions. Based on this finding, a significant inhibitory effect on ADP-induced platelet aggregation was observed upon exposing the platelet-rich plasma (PRP) to the biomimetic UiO-66(Ce) films, prefiguring their wide application potentials in medicine and biotechnology.

18.
J Surg Oncol ; 2020 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-32895951

RESUMO

OBJECTIVE: The aim of this study was to present a novel bile-duct obstructed area imaging (BOAI) and to investigate the feasibility and accuracy of this method in guiding hepatectomy for intrahepatic cholangiocarcinoma (ICC) with intrahepatic biliary obstruction. METHODS: From May 2017 to October 2019, eligible patients who underwent hepatectomy guided by BOAI were enrolled. Perioperative outcomes and operative data were analyzed. To assess the feasibility of BOAI and Glissonean pedicle approach, demarcations based on them were compared. To verify the accuracy of BOAI staining of the target territory, simple linear regression analysis, and intraclass correlation coefficient were used to examine the relationship between predicted resected liver volume (PRLV) and actual resected liver volume (ARLV). RESULTS: BOAI staining achieved valid demarcation in 15 (93.8%) of 16 patients, whereas the ischemic line achieved valid demarcation in only nine patients (57.3%; p = .017). ARLV and PRLV had a strong positive correlation (PRLV = 60.06 + 0.925 × ARLV; R = .945; p = .000). Meanwhile, ARLV (intraclass correlation coefficient = .971) achieved an excellent agreement with PRLV (p < .001). CONCLUSIONS: The novel BOAI staining method can provide valid, feasible, and accurate demarcation line and may be an effective method in the surgical treatment of intrahepatic biliary obstruction.

19.
Eur J Hosp Pharm ; 2020 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-32989000

RESUMO

OBJECTIVE: To analyse the incidence and risk factors of hepatotoxicity induced by antituberculosis (anti-TB) drugs in Renmin Hospital of Wuhan University, and to provide evidence for clinical prevention and treatment of anti-TB drug damage. METHODS: A retrospective analysis of patients who received first-line anti-TB drugs from January 2016 to December 2018 in Renmin Hospital of Wuhan University was conducted. Univariate analysis and binary logistic regression analysis with the forward stepwise method were used to assess the risk factors associated with hepatotoxicity induced by anti-TB drugs. RESULTS: Of the 1603 patients treated with anti-TB drugs, only 1115 patients met the inclusion criteria and 42 subjects developed anti-TB drug-induced hepatotoxicity (ATDH). Significant differences (p<0.05) were seen in age (p=0.042), hypertension (p=0.021), treatment duration (p=0.000) and therapeutic regimen (p=0.001) between the non-ATDH and ATDH groups. Regression analysis further indicated that treatment duration (OR 1.053, 95% CI 1.031 to 1.076, p=0.000) and therapeutic regimens such as isoniazid (H), rifampicin (R), pyrazinamide (Z) and streptomycin (S) (HRZS) (OR 5.751, 95% CI 2.318 to 14.267, p=0.000), HRZ (OR 3.546, 95% CI 1.449 to 8.676, p=0.006) and RZ (OR 12.243, 95% CI 1.181 to 126.862, p=0.036) were risk factors for ATDH. CONCLUSION: The incidence of ATDH in this study was 3.77%, which was lower than that of other hospital-based studies. Treatment duration and therapeutic regimen might be potential risk factors for ATDH during anti-TB therapy in hospital. Among these therapeutic combination regimens, HRZS, HRZ and RZ could significantly increase the occurrence of ATDH when used as anti-TB therapy, while isoniazid, rifampicin and ethambutol (HRE) might be safer.

20.
J Nat Prod ; 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-32989985

RESUMO

Eight new flavonoids, including two ß-hydroxy/methoxychalcones, velutones A and B (1 and 2), two 1,3-diarylpropan-1-ols, velutols C and D (3 and 4), a dihydroxychalcone, velutone E (5), a chalcone, velutone F (6), a furanoflavanone, velutone G (7), and a furanoflavonol, velutone H (8), and 14 known compounds were isolated from Millettia velutina. Their structures were determined by high-resolution electrospray ionisation mass spectrometry (HR-ESIMS) and spectroscopic data analyses and time-dependent density functional theory electronic circular dichroism (TD-DFT-ECD) calculations. Among the isolated constituents, compound 6 exhibited the most potent inhibitory effect (IC50: 1.3 µM) against nigericin-induced IL-1ß release in THP-1 cells. The initial mechanism of action study revealed that compound 6 suppressed NLRP3 inflammasome activation via blocking ASC oligomerization without affecting the priming step, which subsequently inhibited caspase-1 activation and IL-1ß secretion. Most importantly, compound 6 exerted potent protective effects in the LPS-induced septic shock mice model by improving the survival rate of mice and suppressing serum IL-1ß release. These results demonstrated that compound 6 had the potential to be developed as a broad-spectrum NLRP3 inflammasome inhibitor for the treatment of NLRP3-related disease.

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