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1.
Huan Jing Ke Xue ; 42(7): 3263-3271, 2021 Jul 08.
Artigo em Chinês | MEDLINE | ID: mdl-34212652

RESUMO

Increased loads of biogenic and terrestrial natural organic matter into freshwater lakes are projected to be a major consequence of global climate change and cyanobacterial blooms. In this study, the effects of phytoplankton-derived organic matter (POM) and terrestrial humic acid (HA) on the activity, composition, and function of the microbial community in Lake Taihu sediments were investigated. Fluorescent spectra demonstrated that POM with high chemodiversity was composed of labile protein-like components (50%) and recalcitrant humic-like components (50%), while humic-like substances accounted for 97% of HA. Over two-month periods, the organic carbon mineralization in sediments was enhanced owing to increasing NOM concentrations; however, the carbon consumption in POM-amended sediments was significantly higher than that in sediments amended with the same concentrations of HA. Analysis of extracellular polymeric substances indicated that NOM input improved the microbial secretion of proteins and polysaccharides, increasing the aggregation and stability of the microbial community. The amendment of POM also stimulated the activity of organic matter metabolic enzymes, promoting microbial activity. Moreover, 16S rRNA gene sequencing suggested that the mineralization of NOM (especially POM) increased the diversity of the microbial community, favored the survival of Proteobacteria and Bacteroidetes, and upregulated the function genes of organic matter metabolism. These results suggest that the composition and function of microbial community in sediments were associated with the origin, composition, and concentration of NOM input.


Assuntos
Cianobactérias , Microbiota , Sedimentos Geológicos , Substâncias Húmicas/análise , Lagos , RNA Ribossômico 16S
2.
Nat Commun ; 12(1): 4151, 2021 07 06.
Artigo em Inglês | MEDLINE | ID: mdl-34230484

RESUMO

The chemokine receptor CCR5 plays a vital role in immune surveillance and inflammation. However, molecular details that govern its endogenous chemokine recognition and receptor activation remain elusive. Here we report three cryo-electron microscopy structures of Gi1 protein-coupled CCR5 in a ligand-free state and in complex with the chemokine MIP-1α or RANTES, as well as the crystal structure of MIP-1α-bound CCR5. These structures reveal distinct binding modes of the two chemokines and a specific accommodate pattern of the chemokine for the distal N terminus of CCR5. Together with functional data, the structures demonstrate that chemokine-induced rearrangement of toggle switch and plasticity of the receptor extracellular region are critical for receptor activation, while a conserved tryptophan residue in helix II acts as a trigger of receptor constitutive activation.

3.
J Cell Biochem ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34237164

RESUMO

Microtubules play crucial role in process of mitosis and cell proliferation, which have been considered as attractive drug targets for anticancer therapy. The aim of this study was to discover novel and chemically diverse tubulin inhibitors for treatment of cancer. In this investigation, the multilayer virtual screening methods, including common feature pharmacophore model, structure-based pharmacophore model and molecular docking, were developed to screen BioDiversity database with 30,000 compounds. A total of 102 compounds were obtained by the virtual screening, and further filtered by diverse chemical clusters with desired properties and PAINS analysis. Finally, 50 compounds were selected and submitted to the biological evaluation. Among these hits, hits 8 and 30 with novel scaffolds displayed stronger antiproliferative activity on four human tumor cells including Hela, A549, MCF-7, and HepG2. Moreover, the two hits were subsequently submitted to molecular dynamic simulations of 90 ns with the aim of exploring the stability of ligand-protein interactions into the binding pocket, and further probing the mechanism of the interaction between tubulin and hits. The molecular dynamic simulation results revealed there had stronger interactions between tubulin and hits in equilibrium state. Therefore, the hits 8 and 30 have been well characterized as lead compounds for developing new tubulin inhibitors with potential anticancer activity.

4.
Adv Sci (Weinh) ; : e2004850, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34240584

RESUMO

Elevated Wnt/ß-catenin signaling has been commonly associated with tumorigenesis especially colorectal cancer (CRC). Here, an MST4-pß-cateninThr40 signaling axis essential for intestinal stem cell (ISC) homeostasis and CRC development is uncovered. In response to Wnt3a stimulation, the kinase MST4 directly phosphorylates ß-catenin at Thr40 to block its Ser33 phosphorylation by GSK3ß. Thus, MST4 mediates an active process that prevents ß-catenin from binding to and being degraded by ß-TrCP, leading to accumulation and full activation of ß-catenin. Depletion of MST4 causes loss of ISCs and inhibits CRC growth. Mice bearing either MST4T178E mutation with constitutive kinase activity or ß-cateninT40D mutation mimicking MST4-mediated phosphorylation show overly increased ISCs/CSCs and exacerbates CRC. Furthermore, the MST4-pß-cateninThr40 axis is upregulated and correlated with poor prognosis of human CRC. Collectively, this work establishes a previously undefined machinery for ß-catenin activation, and further reveals its function in stem cell and tumor biology, opening new opportunities for targeted therapy of CRC.

5.
Phytother Res ; 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34236105

RESUMO

Erianin is a small-molecule compound that is isolated from Dendrobium chrysotoxum Lindl. In recent years, it has been found to have evident antitumor activity in various cancers, such as bladder cancer, cervical cancer, and nasopharyngeal carcinoma. In this study, we assessed the effect of erianin on lung cancer in terms of cell growth inhibition and the related mechanism. First, erianin at a concentration of less than 1 nmol/L exhibited cytotoxicity in H1975, A549, LLC lung cancer cells, did not cause marked growth inhibition in normal lung and kidney cells, induced obvious apoptosis and G2/M phase arrest of cells, and inhibited the migration and invasion of lung cancer cells in vitro. Second, in a mouse xenograft model of lewis lung cancer (LLC), oral administration of erianin (50, 35, and 10 mg kg-1  day-1 for 12 days) substantially inhibited nodule growth, reduced the fluorescence counts of lewis cells and the percentage vascularity of tumor tissues, increased the number of apoptotic tumor cells, the thymus indices, up-regulated the levels of interleukin (IL)-2 and tumor necrosis factor-α (TNF-α), decreased IL-10 levels and the spleen index, and enhanced immune function. Lastly, the possible targets of erianin were determined by molecular docking and verified via western blot assay. The results indicated that erianin may achieve the above effects via inhibiting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway in vitro and vivo. Taken together, the results showed that erianin had obvious antitumor effects via inhibiting the PI3K/Akt/mTOR pathway in vitro and vivo and may have potential clinical value for the treatment of lung cancer.

6.
Microvasc Res ; : 104225, 2021 Jul 10.
Artigo em Inglês | MEDLINE | ID: mdl-34256086

RESUMO

PURPOSE: Blood-brain barrier (BBB) damage is closely related to various neurological disorders, including bacterial meningitis (BM). Determining a reliable strategy to prevent BBB damage in the context of infection would be highly desirable. In the present study, we investigated the implications of the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) in moderating BBB damage. METHODS: In vitro BBB models were developed by co-culturing hCMEC/D3 cells with glioma cells, whereupon the glioma-exposed endothelial cells (GECs) were treated with a series of mimics, inhibitors, overexpression plasmids, and shRNAs for evaluating whether NEAT1, microRNA-135a (miR-135a) and hypoxia-inducible factor 1α (HIF1α) mediated BBB integrity and permeability. Furthermore, the in vivo biological function of NEAT1 was validated in a mouse model of BBB damage. RESULTS: NEAT1 and HIF1α were determined to be up-regulated, while miR-135a was under-expressed in GECs. As demonstrated by chromatin immunoprecipitation and dual-luciferase reporter assays, NEAT1 could bind to miR-135a, and HIF1α was confirmed as a target of miR-135a. Either overexpression of NEAT1 or depletion of miR-135a impaired the integrity and augmented the permeability of BBB. However, HIF1α silencing could reverse the BBB damage induced by NEAT1 overexpression or by inhibition of miR-135a. In vivo experiments substantiated that knockdown of NEAT1 could alleviate BBB damage in living mice. CONCLUSIONS: Hence, NEAT1 knockdown prevents BBB disruption and exerts promise as a potential target for BM treatment.

7.
Sci Rep ; 11(1): 14472, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34262060

RESUMO

In this study, clubroot resistance in the resynthesized European winter Brassica napus cv. 'Tosca' was introgressed into a Canadian spring canola line '11SR0099', which was then crossed with the clubroot susceptible spring line '12DH0001' to produce F1 seeds. The F1 plants were used to develop a doubled haploid (DH) mapping population. The parents and the DH lines were screened against 'old' pathotypes 2F, 3H, 5I, 6M and 8N of the clubroot pathogen, Plasmodiophora brassicae, as well as against the 'new' pathotypes 5X, 5L, 2B, 3A, 3D, 5G, 8E, 5C, 8J, 5K, 3O and 8P. Genotyping was conducted using a Brassica 15K SNP array. The clubroot screening showed that 'Tosca, '11SR0099' and the resistant DH lines were resistant to three (2F, 3H and 5I) of the five 'old' pathotypes and four (2B, 3O, 8E and 8P) of the 12 'new' pathotypes, while being moderately resistant to the 'old' pathotype 8N and the 'new' pathotypes 3D and 5G. 'Tosca' was susceptible to isolates representing pathotype 3A (the most common among the 'new' pathotypes) as well as pathotypes 6M, 5X, 5L, 5K and 8J. Linkage analysis and QTL mapping identified a ca. 0.88-0.95 Mb genomic region on the A03 chromosome of 'Tosca' as conferring resistance to pathotypes 2F, 3H, 5I, 2B, 3D, 5G, 8E, 3O and 8P. The identified QTL genomic region housed the CRk, Crr3 and CRd gene(s). However, the susceptibility of 'Tosca' to most of the common virulent pathotypes makes it unattractive as a sole CR donor in the breeding of commercial canola varieties in western Canada.

8.
Acta Pharmacol Sin ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34253877

RESUMO

Vacuolar protein sorting 33B (VPS33B) is important for intracellular vesicular trafficking process and protein interactions, which is closely associated with the arthrogryposis, renal dysfunction, and cholestasis syndrome. Our previous study has shown a crucial role of Vps33b in regulating metabolisms of bile acids and lipids in hepatic Vps33b deficiency mice with normal chow, but it remains unknown whether VPS33B could contribute to cholestatic liver injury. In this study we investigated the effects of hepatic Vps33b deficiency on bile acid metabolism and liver function in intrahepatic cholestatic mice. Cholestasis was induced in Vps33b hepatic knockout and wild-type male mice by feeding 1% CA chow diet for 5 consecutive days. We showed that compared with the wild-type mice, hepatic Vps33b deficiency greatly exacerbated CA-induced cholestatic liver injury as shown in markedly increased serum ALT, AST, and ALP activities, serum levels of total bilirubin, and total bile acid, as well as severe hepatocytes necrosis and inflammatory infiltration. Target metabolomics analysis revealed that hepatic Vps33b deficiency caused abnormal profiles of bile acids in cholestasis mice, evidenced by the upregulation of conjugated bile acids in serum, liver, and bile. We further demonstrated that the metabolomics alternation was accompanied by gene expression changes in bile acid metabolizing enzymes and transporters including Cyp3a11, Ugt1a1, Ntcp, Oatp1b1, Bsep, and Mrp2. Overall, these results suggest a crucial role of hepatic Vps33b deficiency in exacerbating cholestasis and liver injury, which is associated with the altered metabolism of bile acids.

9.
Med Chem ; 2021 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-34254924

RESUMO

OBJECTIVE: A series of novel benzimidazole-incorporated naphthalimide derivatives were designed and prepared to overcome the increasing antibiotic resistance. METHOD: The target novel benzimidazole-incorporated naphthalimide derivatives were synthesized from commercial 4-bromo-1,8-naphthalic anhydride and o-phenylene diamine by aminolysis, N-alkylation, and so on. The antimicrobial activity of the synthesized compounds was evaluated in vitro by a two-fold serial dilution technique. The interaction of compound 10g with Salmonella typhimurium DNA was studied using UV-vis spectroscopic methods. RESULTS: Compound 10g bearing a 2,4-dichlorobenzyl moiety exhibited the best antimicrobial activities in this series relatively, especially it gave the comparable action against Salmonella typhimurium compared to the reference drug Norfloxacin (MIC = 4 mg/mL). Further research showed that compound 10g could effectively intercalate into the Salmonella typhimurium DNA to form the 10g-DNA complex, which might correlate with the inhibitory activity. Molecular docking results demonstrated that naphthalimide compound 10g could interact with base-pairs of DNA hexamer duplex by p-p stacking. Additionally, the combinations of the solid active combination with clinical drugs gave better antimicrobial efficiency with less dosage and broader antimicrobial spectrum than the separated use alone. Notably, these combined systems were more sensitive to Fluconazole-insensitive M. ruber. CONCLUSION: This work opened up a good starting point to optimize the structures of benzimidazole-incorporated naphthalimide derivatives as potent antimicrobial agents.

10.
Clin Nutr ; 40(7): 4538-4550, 2021 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-34229258

RESUMO

BACKGROUND & AIMS: Previous randomized controlled trials (RCTs) have compared the effects of pure preparations of eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) in reducing metabolic syndrome (MetS) risk factors, but the results were inconsistent. The present study aimed to clarify whether EPA and DHA have differential effects on MetS features in humans. METHODS: A systematic literature search was conducted in CNKI, PubMed, Embase and Scopus updated to February 2021. The mean changes in the characteristics of MetS were calculated as weighted mean differences by using a random-effects model. Thirty-three RCTs were included. RESULTS: The results showed that both EPA and DHA were effective at lowering serum triglycerides (TG) levels. EPA supplementation decreased the serum levels of total cholesterol (TC) (WMD = -0.24 mmol/L; 95% CI, -0.43, -0.05 mmol/L), TG (WMD = -0.77 mmol/L; 95% CI, -1.54, -0.00 mmol/L) and low density lipoprotein-cholesterol (LDL-C) (WMD = -0.13 mmol/L; 95% CI, -0.25, -0.01 mmol/L), while DHA increased the serum levels of TC (WMD = 0.14 mmol/L; 95% CI, 0.03, 0.25 mmol/L), LDL-C (WMD = 0.26 mmol/L; 95% CI, 0.15, 0.38 mmol/L) and high density lipoprotein-cholesterol (HDL-C) (WMD = 0.07 mmol/L; 95% CI, 0.04, 0.09 mmol/L). Moreover, DHA increased the serum levels of insulin compared with EPA, especially in subgroups whose mean age was <60 years (0.43 mU/L; 95% CI: 0.04, 0.81 mU/L) and duration of DHA supplementation < 3 months (0.39 mU/L; 95% CI: 0.01, 0.77 mU/L). CONCLUSIONS: The present meta-analysis provides evidence that EPA and DHA have different effects on risk factors of MetS.

11.
Med Phys ; 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34287941

RESUMO

PURPOSE: Research regarding cellular responses at different oxygen concentrations (OCs) is of immense interest within the field of radiobiology. Therefore, this study aimed to develop a mechanistic model to analyze cellular responses at different OCs. METHODS: A DNA damage model (the different cell oxygen level DNA damage [DICOLDD] model) that examines the oxygen effect was developed based on the oxygen fixation hypothesis, which states that dissolved oxygen can modify the reaction kinetics of DNA-derived radicals generated by ionizing radiation. The generation of DNA-derived radicals was simulated using the Monte Carlo method. The decay of DNA-derived radicals due to the competing processes of chemical repair, oxygen fixation, and intrinsic damaging using differential equations. The DICOLDD model was fitted to previous experimental data obtained under different irradiation configurations and validated by calculating yields of DNA double strand breaks (DSBs) after exposure to 137 Cs as well as cell survival fractions (SFs) using a mechanistic model of cellular survival. Moreover, we used the DICOLDD model to calculate DNA DSB damage yields after irradiation with 0.5-50 MeV protons. RESULTS: Generally, DSB yields calculated after exposure to 137 Cs at different OCs correspond to statistical uncertainties of previous experimental results. Calculated SFs of CHO and V79 cells exposed to photons, protons, and alpha particles at different OCs generally concur with those obtained in previous studies. Our results demonstrated that the variation in DSB yields was less than 10% when the cellular OC decreased from 21% to 5%. Additionally, DSB yields changed drastically when OC dropped below 1%. CONCLUSIONS: We developed a DNA damage model to evaluate the oxygen effect and provide evidence that a reaction-kinetic model of DNA-derived radicals induced by ionizing radiation suffices to explain the observed oxygen effects. Therefore, the DICOLDD model is a powerful tool for the analysis of cellular responses at different OCs after exposure to different types of radiation.

12.
Psychophysiology ; : e13900, 2021 Jul 20.
Artigo em Inglês | MEDLINE | ID: mdl-34287947

RESUMO

The goal of the current study was to investigate the moderating effect of tonic respiratory sinus arrhythmia (RSA) in the relation between childhood maltreatment and depression symptoms among young adults. A total of 98 participants (70 women) aged 17-22 years completed questionnaires on childhood maltreatment and depressive symptoms. RSA data were obtained during a resting condition in the laboratory. Results indicated that childhood maltreatment interacted with tonic RSA to predict depressive symptoms, even after controlling for age and body mass index (BMI) of each participant. Specifically, higher levels of childhood maltreatment were associated with higher levels of depressive symptoms, but only among young adults who exhibited lower tonic RSA. The results indicated that the association between childhood maltreatment and depressive symptoms depends on young adults' physiological functioning/flexibility. Findings suggest that consideration of external environmental factors in combination with internal physiological factors is critical to understand young adults' mental health.

13.
Mol Med ; 27(1): 73, 2021 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-34238206

RESUMO

BACKGROUND: Circular RNAs (circRNAs) play critical roles in the development of atherosclerosis (AS). This study investigated the role of circMTO1 in the progression of AS. METHODS: Serum samples from AS patients and healthy volunteers and vascular smooth muscle cells (VSMCs) were used as the study materials. The expressions of circMTO1 and miR-182-5p were measured by RT-qPCR. The effects of circMTO1, miR-182-5p, and RASA1 on VSMC proliferation and apoptosis were examined by MTT and BrdU assays and wound healing and flow cytometric analyses, respectively. Downstream target genes of circMTO1 and miR-182-5p were predicted using target gene prediction and screening and confirmed using a luciferase reporter assay. RASA1 expression was detected by RT-qPCR and Western blot. RESULTS: circMTO1 expression was decreased, while miR-182-5p expression was increased in human AS sera and oxidized low-density lipoprotein (ox-LDL)-stimulated VSMCs. CircMTO1 overexpression inhibited the proliferation and promoted the apoptosis of ox-LDL-stimulated VSMCs. CircMTO1 was found to be served as a sponge of miR-182-5p and RASA1 as a target of miR-182-5p. Moreover, circMTO1 acted as a ceRNA of miR-182-5p to enhance RASA1 expression. Furthermore, miR-182-5p overexpression and RASA1 knockdown reversed the effects of circMTO1 overexpression on the proliferation, migration, and apoptosis of ox-LDL-stimulated VSMCs. CONCLUSION: CircMTO1 inhibited the proliferation and promoted the apoptosis of ox-LDL-stimulated VSMCs by regulating miR-182-5p/RASA1 axis. These results suggest that circMTO1 has potential in AS treatment.

14.
Food Funct ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251375

RESUMO

In this study, the immunomodulatory effect of sea buckthorn (SBT) pulp oil was elucidated in immunosuppressed Balb/c mice induced by cyclophosphamide (CTX). The results showed that SBT pulp oil could reverse the decreasing trend of body weight, thymus/spleen index and hematological parameters induced by CTX. Compared with immunosuppressive mice induced by CTX, SBT pulp oil could enhance NK cytotoxicity, macrophage phagocytosis, and T lymphocyte proliferation, and regulate the proportion of T cell subsets in mesenteric lymph nodes (MLN), and promote the production of secretory immunoglobulin A (sIgA), IFN-γ, IL-2, IL-4, IL-12 and TNF-α in the intestines. In addition, SBT pulp oil can promote the production of short fatty acids (SCFAs), increase the diversity of gut microbiota, improve the composition of intestinal flora, increase the abundance of Alistipes, Bacteroides, Anaerotruncus, Lactobacillus, ASF356, and Roseburia, while decreasing the abundance of Mucispirillum, Anaeroplasma, Pelagibacterium, Brevundimonas, Ochrobactrum, Acinetobacter, Ruminiclostridium, Blautia, Ruminiclostridium, Oscillibacter, and Faecalibaculum. This study shows that SBT pulp oil can regulate the diversity and composition of intestinal microflora in CTX-induced immunosuppressive Balb/c mice, thus enhancing the intestinal mucosa and systemic immune response. The results can provide a basis for understanding the function of SBT pulp oil and its application as a new probiotic and immunomodulator.

15.
Aging (Albany NY) ; 13(undefined)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34270462

RESUMO

The FXYD gene family comprises seven members that encode a class of small-membrane proteins characterized by an FXYD motif and interact with Na+/K+-ATPase. Until now, the expression patterns and prognostic roles of the FXYD family in colon cancer (CC) have not been systematically reported. Gene expression, methylation, clinicopathological features and the prognoses of CC patients were obtained from The Cancer Genome Atlas (TCGA) database. The expression feature and prognostic values of FXYD members were identified. Gene set enrichment analysis (GSEA) was performed to explore the potential mechanism underlying the function of the FXYD family in CC. Tumor Immune Estimation Resource (TIMER) and CIBERSORT analysis were used to assess the correlations between FXYD family members and tumor immune infiltrating cells (TIICs). FXYD family members were differentially expressed in CC except for FXYD2. FXYD2, FXYD3 and FXYD4 were revealed as independent prognostic factors for recurrence, while FXYD3 and FXYD7 were identified as prognostic factors for survival according to univariate and multivariate analyses with Cox regression. GSEA revealed that FXYD family members were involved in complicated biological functions underlying cancer progression. TIMER and CIBERSORT analyses showed significant associations between FXYD family genes and TIICs. The present study comprehensively revealed the expression mode and prognostic value of FXYD members in CC, providing insights for further study of the FXYD family as potential clinical biomarkers in CC.

16.
Blood Press Monit ; 2021 Jul 13.
Artigo em Inglês | MEDLINE | ID: mdl-34267074

RESUMO

OBJECTIVE: The aim of this study was to investigate whether declining mobility and muscle strength predict new-onset hypertension in suburban-dwelling elderly individuals. METHODS: This study was designed as a longitudinal prospective cohort study. It was comprised of 362 individuals (mean age = 67.8 ± 6.2; 157 men) without hypertension at baseline. At baseline, all participants completed health questionnaires and underwent measurements of mobility [the Timed Up and Go test (TUGT) and 4-m walking test] and muscle strength (grip strength). At 1-year follow-up, we determined the number of participants who had developed new-onset hypertension. We then evaluated the relationship between above metrics and the development of hypertension. RESULTS: In the present study, 94 (26.0%) participants developed hypertension after 1 year. After adjusting for mixed factors, the TUGT scores [hazard ratio = 1.15; 95% confidence interval (CI), 1.10-1.31; P = 0.030] were positively associated with the development of hypertension, while the 4-m walking test scores (hazard ratio = 0.07; 95% CI, 0.01-0.47; P = 0.007) showed an inverse relationship with hypertension incidence. Grip strength (hazard ratio = 1.03; 95% CI, 0.99-1.06; P = 0.098) was not significantly associated with hypertension incidence. CONCLUSION: Our results indicate that people with declining mobility are significantly more likely to develop hypertension. Hence, improving mobility could be protective against hypertension for elderly individuals.

17.
J Cancer Res Ther ; 17(3): 771-776, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34269312

RESUMO

Purpose: The replication protein A3 (RPA3) is a subunit of the RPA protein complex, which plays an essential role in multiple processes of DNA metabolism. However, the involvement of RPA3 bladder urothelial carcinoma (UC) prognosis has not yet been elucidated. The aim of our study is to investigate the prognostic role of RPA3 expression in patients with bladder UC. Materials and Methods: Bladder UC tissue specimens from 155 consecutively treated patients who underwent surgery between 2013 and 2018 were evaluated. The RPA3 expression was determined by immunohistochemistry, Western blot, and correlated with clinicopathological parameters. The prognostic significance of RPA3 expression was explored using the univariate and multivariate survival analysis of 155 patients who were followed. Results: A total of 155 tissue specimens "of patients" who were regularly followed with the mean 39.6 months (from 4 to 71 months). The expression of RPA3 was significantly associated with tumor grade (P = 0.031) and stage (P = 0.021), as well as tumor size (P = 0.034). In univariate analysis, RPA3 overexpression showed an unfavorable influence on recurrence-free survival with statistical significance (P < 0.01). TNM stage and grade also showed strong statistical relation with adverse recurrence-free survival (P < 0.01, P = 0.030). Multivariate analysis revealed that grade, stage, and RPA3 reactivity (P = 0.025, P < 0.01, P = 0.016) were identified as independent prognostic factors for recurrence-free survival in patients with bladder UC. Conclusions: These results of this study proved that elevated expression of RPA3 was associated with worse clinical outcome in bladder UC patients. This finding suggested that RPA3 served as a potential prognostic biomarker, which could be useful to predict cancer evolution and may represent a novel therapeutic target for the intervention of bladder UC patients.

18.
J Orthop Surg Res ; 16(1): 438, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34233695

RESUMO

BACKGROUND: Medial open wedge high tibial osteotomy (OWHTO) may result in lower limb discrepancy (LLD), and some patients experience uncomfortable symptoms. Studies have found that the degree of LLD is one but not the only high-risk factor for inducing symptoms. The main purpose of this study is to explore the risk factors for symptomatic LLD. METHODS: Sixty-four patients who underwent OWHTO in our hospital between June 2018 and January 2020 were included in the study. Changes in tibia length, lower limb length, femorotibial angle (FTA), LLD, and KOOS score were evaluated before and 1 year after surgery. Questionnaire was used to investigate whether patients had uncomfortable symptoms of LLD after surgery. Binary logistic regression was applied to analyze the risk factors of symptomatic LLD. RESULTS: There were 18 patients with subjective LLD uncomfortableness, 13 of them were occasional and 5 were frequent. Patients had a mean correction angle of 11.7° ± 4.6°, with a mean increase in tibial length of 6.0 ± 3.5 mm, lower limb length of 7.5 ± 2.3 mm, and LLD of 6.9 ± 4.2 mm at 1 year post-operation. Preoperative and postoperative changes in tibia length and lower limb length were statistically significant (P < 0.0001).There were statistically significant differences in pain, symptoms, ADL, sports/recreations, QOL of KOOS subclassification before and after surgery (P < 0.0001). Binary logistic regression revealed that age ≥ 55, BMI ≥ 28, and LLD ≥ 10 mm were high-risk factors for symptomatic LLD (P = 0.031, OR = 4.82; P = 0.012, OR = 6.251; P = 0.006, OR = 6.836). CONCLUSION: Patients with age ≥ 55, BMI ≥ 28, and postoperative LLD ≥ 10 mm are more likely to develop symptomatic LLD. Older or heavier patients, who are expected to have an LLD greater than 10 mm after OWHTO should be fully informed of the possibility of postoperative LLD symptoms.

19.
Molecules ; 26(11)2021 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-34205200

RESUMO

Excessive use of nitrogen fertilizer in intensively managed agriculture has resulted in abundant accumulation of nitrate in soil, which limits agriculture sustainability. How to reduce nitrate content is the key to alleviate secondary soil salinization. However, the microorganisms used in soil remediation cause some problems such as weak efficiency and short survival time. In this study, seaweed polysaccharides were used as stimulant to promote the rapid growth and safer nitrate removal of denitrifying bacteria. Firstly, the growth rate and NO3--N removal capacity of three kinds of denitrifying bacteria, Bacillus subtilis (BS), Pseudomonas stutzeri (PS) and Pseudomonas putida (PP), were compared. The results showed that Bacillus subtilis (BS) had a faster growth rate and stronger nitrate removal ability. We then studied the effects of Enteromorpha linza polysaccharides (EP), carrageenan (CA), and sodium alginate (AL) on growth and denitrification performance of Bacillus subtilis (BS). The results showed that seaweed polysaccharides obviously promoted the growth of Bacillus subtilis (BS), and accelerated the reduction of NO3--N. More importantly, the increased NH4+-N content could avoid excessive loss of nitrogen, and less NO2--N accumulation could avoid toxic effects on plants. This new strategy of using denitrifying bacteria for safely remediating secondary soil salinization has a great significance.


Assuntos
Bactérias/crescimento & desenvolvimento , Nitratos/metabolismo , Polissacarídeos/farmacologia , Alga Marinha/química , Bacillus subtilis/crescimento & desenvolvimento , Bacillus subtilis/metabolismo , Bactérias/metabolismo , Biodegradação Ambiental , Desnitrificação , Pseudomonas putida/crescimento & desenvolvimento , Pseudomonas putida/metabolismo , Pseudomonas stutzeri/crescimento & desenvolvimento , Pseudomonas stutzeri/metabolismo , Solo/química , Microbiologia do Solo
20.
Curr Protoc ; 1(7): e186, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34232571

RESUMO

Protein glycosylation is one of the most common and diverse modifications. Aberrant protein glycosylation has been reported to associate with various diseases. High-throughput and comprehensive characterization of glycoproteins is crucial for structural and functional studies of altered glycosylation in biological, physiological, and pathological processes. In this protocol, we detail a workflow for comprehensive analyses of intact glycopeptides (IGPs), glycosylation sites, and glycans from N-linked glycoproteins. By utilizing liquid handling systems, our workflow could enrich IGPs in a high-throughput manner while reducing sample processing time and human error involved in traditional proteomics sample processing techniques. Together, our workflow enables a high-throughput enrichment of glycans, glycosites, and intact glycopeptides from complex biological or clinical samples. © 2021 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Enzymatic digestion of glycoproteins using C4-tips Basic Protocol 2: Intact glycopeptide analysis using C18/MAX-tips Basic Protocol 3: Glycan and glycosite analysis.


Assuntos
Glicopeptídeos , Espectrometria de Massas em Tandem , Glicopeptídeos/metabolismo , Glicoproteínas , Glicosilação , Humanos , Polissacarídeos
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