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1.
Ying Yong Sheng Tai Xue Bao ; 32(7): 2290-2300, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34313045

RESUMO

How to accurately model species macro-richness patterns and endemism centers is a key focus of biodiversity conservation efforts and a hot biogeographical topic. Southwest China is one of regions with high Fagaceae species richness, the species diversity patterns and driving mechanisms are unclear. In this study, the distribution pattern of species richness (SR), weighted endemism (WE), and corrected weighted endemism (CWE) indices were estimated based on 7258 occurrence points of 161 Fagaceae species in Southwest China using both occurrence-to grid method and species distribution model (SDM). We used the spatial autoregressive (SAR) model to analyze the relationship between diversity indices and environmental factors. Overall, the three SDM-simulated diversity indices were more continuous in values than that of the occurrence-to grid method, though the distributions of those indices obtained by the two methods were similar. The areas with high SR value were mainly distributed in the south edge of Yunnan, north Guangxi and southwest Guangxi (62-89 species). The maximum of WE concentrated in south Yunnan and west Guangxi (1.77-5.02). The highest CWE (0.07-0.17) was found in southeast Tibet, Qinling-Daba Mountains, southwest Guangxi, and southeast Yunnan. The SAR models showed significant effect of precipita-tion in the driest month, standard deviations of seasonal temperature, altitude range and soil organic carbon content on SR. The effects of precipitation in the driest month, standard deviations of seaso-nal temperature, potential evaporation and altitude range on the WE were significant. The precipitation in the driest month, standard deviations of seasonal temperature, historical temperature change, coefficient of variation of enhanced vegetation index and altitude variation had significant effects on the CWE. The R2 of SAR model for SR, WE and CWE was 0.857, 0.733, 0.593, respectively, being higher than that of ordinary least squares (OLS) (R2=0.689, 0.425, 0.422). In conclusion, water availability, climate seasonality, habitat heterogeneity, historical climate change and soil condition were the most important factors limiting the distribution of SR and WE of Fagaceae in Southwest China. The SR and WE centers of Fagaceae were located in south and southeast Yunnan, southwest Guangxi, west Guangxi, Qinling-Daba Mountains, and southeast Tibet, where should be adequately protected.

2.
Pest Manag Sci ; 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34314099

RESUMO

BACKGROUND: Botanical pesticides play an important role in organic agricultural practices and are widely used in integrated pest management (IPM). U. grandiflora was mainly reported as traditional medicines and possessed antibacterial, antioxidant, and antiprotozoal activities. Therefore, important biological activities of U. grandiflora may suggest that they have potentials to be used as botanical pesticides. RESULTS: The extract of Uvaria grandiflora exhibited broad-spectrum inhibitory activity toward phytopathogenic fungi and oomycetes, particularly against Colletotrichum musae and Phytophthora capsici, and its secondary metabolite zeylenone also displayed strong antifungal and anti-oomycete activities against phytopathogens. Particularly, EC50 values of zeylenone against P. capsici and C. musae were 6.98 and 3.37 µgmL-1 , showing better inhibitory effects than those of commercial fungicides (azoxystrobin and osthole). Additionally, the pot experiments showed that the extract of U. grandiflora could effectively control Pseudoperonospora cubensis, Phytophthora infestans, P. capsici and Podosphaera xanthii. In the field experiment, 5% microemulsion of U. grandiflora extract exhibited 79.72% efficacy against cucumber powdery mildew at 87.5 g/ha on the 14th day after two sprayings, which was better than that of 21.5% trifloxystrobin and 21.5% fluopyram SC at 200.9 g/ha. Surprisingly, 5% microemulsion of U. grandiflora extract could promote cucumber growth significantly. Furthermore, the action mechanism analysis indicated that zeylenone may damage the cytoderm and affect energy metabolism of P. capsici. CONCLUSION: It is the first time to discover that the extract of U. grandiflora and zeylenone have broad application prospects in the development as botanical fungicides. This article is protected by copyright. All rights reserved.

3.
Anal Chem ; 93(29): 10132-10140, 2021 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-34255490

RESUMO

Herein, SnTe nanobelts (NBs) with efficient oxidase-mimetic activity were synthesized by the simple electrochemical exfoliation method. A specific inhibition effect of Cl- on the enzymatic behavior of the pure SnTe NBs was discovered, which was accordingly used for establishing a highly feasible, sensitive, selective, and stable Cl- colorimetric assay. The detection concentration range was 50 nM to 1 mM, and the lowest detection limit was 20 nM for Cl-. In addition, a signal on-off-on route based on the SnTe NB nanozyme was designed to realize the reliable and specific detection of Hg2+. Therein, the SnTe NBs were grafted with gold nanoparticles to form a hybrid of SnTe/Au, resulting in the depression of the oxidase-like activity, which can then be recovered in the presence of the Hg2+ due to the formation of a gold amalgam. Especially, it was found that the high concentration of Cl- over 3 mM could again exert suppression influence toward the enzymatic activity of the SnTe/Au-Hg system. Based on the to-love-and-to-kill interaction between Cl- and Hg2+, the detection range for Cl- can be extended to 40 to 250 mM. In return, the assays of Cl- could avoid in advance its interference toward the accurate Hg2+ assays. We systematically clarified the oxidase-like catalytic mechanism of the SnTe-derived nanozyme systems. The as-proposed colorimetry can be successfully applied in practical samples including the sweat, human serum, or seawater/tap water, relating to cystic fibrosis, hyper-/hypochloremia, or environmental control, respectively.

4.
Int J Biol Macromol ; 186: 639-648, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34273340

RESUMO

Zeolite imidazole framework materials (ZIFs) are a new type of antibacterial material with high chemical and thermal stability, and good antibacterial effect. However, powder ZIFs materials have the disadvantages of difficult separation and easy aggregation, which limit their application. In this work, ZIFs and chitosan (CS) were compounded by in-situ growth method to prepare a new antibacterial agent. The synergism of CS and ZIFs can effectively promote antibacterial effect compared with CS and pristine ZIFs, and CS/ZIF-67(1:6) has the best antibacterial activity, and its inhibitory rate (in 15 h) of E. coli is 96.75%, and the inhibitory rate of S. aureus reaches as high as 100%. This composites can effectively cause bacterial cell membrane rupture and leakage of internal nucleic acid and protein, leads to achieve antibacterial effect, and also exhibit excellent long-term (at least 5 days) antibacterial properties, the leaching of cobalt is below than 0.5 mg·L-1, and this composites are with excellent bio-compatibility.

5.
Int Immunopharmacol ; 98: 107906, 2021 Jun 28.
Artigo em Inglês | MEDLINE | ID: mdl-34198238

RESUMO

The functional state of T cells is diverse and under dynamic control for adapting to the changes of microenvironment. Reversible protein phosphorylation represents an important post-translational modification that not only involves in the immediate early response of T cells, but also affects their functionality in the long run. Perturbation of global phosphorylation profile and/or phosphorylation of specific signaling nodes result in aberrant T cell activity. Dual specific phosphatases (DUSPs), which target MAPKs and beyond, have increasingly been emerged as a versatile regulator in T cell biology. Herein in this mini review, we sought to summarize and discuss the impact of DUSP proteins on the regulation of effector T cell activity, T cell polarization, regulatory T cell development and T cell senescence/exhaustion. Given the distinctive engagement of each DUSP member under various disease settings such as chronic infection, autoimmune disorders, cancer and age-related diseases, DUSP proteins likely hold the promise to become a druggable target other than the existing therapeutics that are predominantly by manipulating protein kinase activity.

6.
Adv Ther ; 2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34308513

RESUMO

INTRODUCTION: Spontaneous bacterial peritonitis (SBP) is a common infection in patients with hepatitis B virus (HBV)-related acute-on-chronic liver failure (ACLF). SBP significantly increases the mortality rate and medical costs. The association between proton pump inhibitor (PPI) use and SBP remains unclear. We conducted a retrospective study to investigate the association between PPI use and SBP in patients with HBV-related ACLF and to explore the risk factors for SBP. METHODS: We compared the SBP incidence between the PPI and non-PPI groups before and after propensity score matching and explored the association between the duration and type of PPI and SBP occurrence. Risk factors for SBP occurrence were determined by univariate and multivariate logistic regression analysis. RESULTS: The SBP incidence was higher in the PPI group than in the non-PPI group before and after propensity score matching. The SBP incidence increased for elevated MELD scores in PPI users. There was a similar SBP incidence in both different types and durations of PPI users. MELD score, old age, male sex, and high WBC count were significant independent risk factors for SBP in PPI users with HBV-related ACLF in the hospital. CONCLUSIONS: PPI therapy increases the risk of SBP development in patients with HBV-related ACLF. MELD score, old age, male sex, and high WBC count could serve as predictors of SBP in PPI users. Caution should be taken regarding PPI use, especially for patients with MELD scores > 30.

7.
Nutr Cancer ; : 1-11, 2021 Jul 26.
Artigo em Inglês | MEDLINE | ID: mdl-34309475

RESUMO

The identification and management of malnutrition is increasingly considered as an important issue in cancer treatment. This study aimed at determining the prevalence of malnutrition among elderly inpatients with gastrointestinal cancer. Meanwhile, the exact relationship between nutrition and frailty was explored. The presence of malnutrition was determined using Mini-Nutritional Assessment Short Form (MNA-SF), Nutrition Risk Screening 2002 (NRS2002), and a batch of laboratory parameters. A cross-sectional study of 265 eligible elderly inpatients with gastrointestinal cancer was conducted. The results showed that the prevalence of malnutrition classified by MNA-SF, NRS2002, albumin, prealbumin, total protein, hemoglobin, and total lymphocyte count were 66.8%, 68.7%, 41.5%, 27.9%, 39.2%, 40.8%, and 15.5%, respectively. There was a fair agreement between MNA-SF and NRS2002 (Kappa = 0.335, P < 0.001) in screening malnutrition. According to the albumin criterion, both MNA-SF and NRS2002 exhibited better sensitivity (72.7% and 76.4%, respectively) but poor specificity (37.4% and 36.8%, respectively) in screening malnutrition. A significant linear correlation between MNA-SF (NRS2002) and frailty was discovered (ß=-0.259 and ß = 0.412, respectively, P < 0.001). By identifying malnutrition in this elderly population, targeted plans can be developed as a part of cancer treatment and care. A better nutritional screening tool with both high sensitivity and specificity should be selected or developed.

8.
Sci Transl Med ; 13(603)2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290056

RESUMO

Abdominal aortic aneurysm (AAA) is a potentially fatal vascular disease, but the underlying mechanisms remain unknown. Here, we tested the hypothesis that erythropoietin (EPO) may promote the formation of AAA. We found that EPO dose-dependently promoted the formation of AAA in both Apoe -/- (66.7%) and wild-type (WT) (60%) mice receiving a high dose of EPO. EPO monoclonal antibodies given to Apoe -/- mice receiving angiotensin II (AngII) stimulation resulted in a markedly lower incidence of AAA (from 86.7 to 20%, P < 0.001), and EPO receptor (EPOR) knockdown in Epor +/- Apoe -/- mice substantially reduced the incidence of AAA compared to Apoe -/- mice after AngII stimulation (from 86.7 to 45.5%, P < 0.05), further supporting the finding that EPO is a contributor to AAA formation. EPO-induced AAA resulted in increased microvessels, phagocyte infiltration, and matrix metalloproteinase secretion, as well as reduced collagen and smooth muscle cells (SMCs). Experiments in vitro and ex vivo demonstrated that EPO induced proliferation, migration, and tube formation of endothelial cells via the JAK2/STAT5 signaling pathway. In humans, serum EPO concentrations were higher in patients with AAA than in healthy individuals and correlated with the size of the AAA, suggesting a potential link between EPO and the severity of AAA in humans. In conclusion, we found that EPO promotes the formation of AAA in both Apoe -/- and WT mice by enhancing angiogenesis, inflammation, collagen degradation, and apoptosis of SMCs and that EPO/EPOR signaling is essential for AngII-induced AAA. The association between EPO and AAA in humans warrants further study.

9.
Artigo em Inglês | MEDLINE | ID: mdl-34254242

RESUMO

In order to realize the utilization of Moutai lees and the improvement of soil fertility of yellow soil in Guizhou, a field experiment was carried out to study the effects of short-term application of Moutai lees biochar on nutrients and fungal community structure diversity of yellow soil. The results showed that the application of Moutai lees biochar increased the pH, soil organic matter (SOM), total nitrogen (TN), ammonium nitrogen (NH4+-N), nitrate nitrogen (NO3--N), available phosphorus (AP), and available potassium (AK), while the microbial biomass carbon (MBC) and microbial biomass nitrogen (MBN) were reduced. The application of biochar significantly reduced the number of fungal OTU and community diversity. The application of biochar increased the relative abundances of Chytridiomycota and Mortierellomycota, while the relative abundance of Ascomycota was significantly reduced. Redundancy analysis (RDA) suggested that SOM, NH4+-N and NO3--N were the key factors correlated with changes in microbial community structure. Overall, the short-term application of lees biochar can not only improve the nutrient content of yellow soil, but also change the structure and diversity of soil fungal communities. More importantly, Moutai lees biochar can reduce the relative abundance of some pathogenic fungi and play the role of inhibiting the growth and reproduction of harmful plant pathogens.

10.
Artigo em Inglês | MEDLINE | ID: mdl-34209072

RESUMO

Higher education institutions (HEIs), among other social systems, have an irreplaceable role in combating COVID-19. However, we know little about institutional and individual factors that might facilitate university students' beliefs and behaviors toward preventive behaviors for COVID-19 within the higher education context. Our study applies an extended theory of planned behavior (TPB) model to investigate the structural relationships among the institutional climate, attitudes, subjective norms, perceived behavioral control and preventive behaviors of university students and to detect the moderating impacts of perceived risk on the structural model. Data were collected from 3693 university students at 18 universities in Beijing, China through an online survey. Structural equation modeling (SEM) and multigroup analysis were performed to examine the empirical model. The results reveal that (1) the institutional climate has a significant, direct effect on preventive behaviors for COVID-19 among university students, (2) the TPB components, namely attitudes, subjective norms and perceived behavioral control, partially mediate the relationship between the institutional climate and preventive behaviors for COVID-19, and (3) perceived risk moderates several paths in the model. Theoretical and practical implications are offered, and recommendations for future research are outlined.


Assuntos
COVID-19 , Universidades , Pequim , China , Humanos , Intenção , SARS-CoV-2 , Estudantes , Inquéritos e Questionários
11.
Food Chem ; 364: 129583, 2021 Mar 21.
Artigo em Inglês | MEDLINE | ID: mdl-34225247

RESUMO

One of the major concerns in the application of nanocarriers in biosensing is the impair of the recognition molecules bioactivity loaded on their surfaces due to harsh and laborious cross-linking and random orientation, resulting in unsatisfactory sensitivity. Herein, we proposed a novel immunochromatographic test strip (FNS-ag-DICTS) by taking advantage of the antigen (ag) modified Fe2O3 nanostructures (FNSs) as new signal tags and goat anti-mouse IgG labeling on the detection line instead of ag, which was used for sensitive detection of aflatoxin B1 (AFB1). The fabricated FNS-ag can orientate the Fab region of monoclonal antibodies (mAbs), waiving the intrinsic limitations of traditional nanomaterials labeled mAbs. Under optimal conditions, FNS-ag-DICTS possessed excellent specificity and a wide detection range, with a visual limit of detection (vLOD) of 0.0125 ng mL-1. In addition, the biosensor successfully detected AFB1 in peanut, green bean and corn, with an average recovery rate of 82.8-124.9%.

12.
J Med Chem ; 64(14): 10333-10349, 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34196551

RESUMO

Targeting the menin-MLL protein-protein interaction is being pursued as a new therapeutic strategy for the treatment of acute leukemia carrying MLL-rearrangements (MLLr leukemia). Herein, we report M-1121, a covalent and orally active inhibitor of the menin-MLL interaction capable of achieving complete and persistent tumor regression. M-1121 establishes covalent interactions with Cysteine 329 located in the MLL binding pocket of menin and potently inhibits growth of acute leukemia cell lines carrying MLL translocations with no activity in cell lines with wild-type MLL. Consistent with the mechanism of action, M-1121 drives dose-dependent down-regulation of HOXA9 and MEIS1 gene expression in the MLL-rearranged MV4;11 leukemia cell line. M-1121 is orally bioavailable and shows potent antitumor activity in vivo with tumor regressions observed at tolerated doses in the MV4;11 subcutaneous and disseminated models of MLL-rearranged leukemia. Together, our findings support development of an orally active covalent menin inhibitor as a new therapy for MLLr leukemia.

13.
Int J Biochem Cell Biol ; 137: 106033, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34216755

RESUMO

In clinical treatment, there is increasingly prevalent that traditional Chinese medicine treats common bone diseases including osteoporosis. Hydroxysafflor yellow A (HSYA), one of the essential compounds of Safflower, has been used as the therapy for thrombus, myocardial ischemia, and inflammation, but its effect on osteogenesis through epigenetic control and ovariectomy-induced bone loss in vivo has not been explored. Therefore, the study aimed to explore the function and mechanism of HSYA on bone formation and development. We found HSYA could enhance the cell viability and promote osteogenesis of hBMSCs in vitro. Mechanistically, HSYA could increase the expression of ß-catenin leading to its accumulation in the nucleus and activation of downstream targets to promote osteogenesis. Besides, RNA-seq and quantitative RT-PCR and western blot showed KDM7A was significantly increased by HSYA. The occupancy of H3K27me2 on ß-catenin promoter was significantly decreased by HSYA, which could be reversed by silencing endogenous KDM7A. More importantly, HSYA promoted bone development in chick embryos and prevented ovariectomy (OVX)-induced bone loss in SD rats. Taken together, our study has shown convincing evidence that HSYA could promote osteogenesis and bone development via epigenetically regulating ß-catenin and prevent ovariectomy-induced bone loss.

14.
J Transl Med ; 19(1): 313, 2021 Jul 19.
Artigo em Inglês | MEDLINE | ID: mdl-34281583

RESUMO

BACKGROUND: The exploration of genomic alterations in Chinese colorectal liver metastasis (CRLM) is limited, and corresponding genetic biomarkers for patient's perioperative management are still lacking. This study aims to understand genome diversification and complexity that developed in CRLM. METHODS: A custom-designed IDT capture panel including 620 genes was performed in the Chinese CRLM cohort, which included 396 tumor samples from metastatic liver lesions together with 133 available paired primary tumors. RESULTS: In this Chinese CRLM cohort, the top-ranked recurrent mutated genes were TP53 (324/396, 82%), APC (302/396, 76%), KRAS (166/396, 42%), SMAD4 (54/396, 14%), FLG (52/396, 13%) and FBXW7 (43/396, 11%). A comparison of CRLM samples derived from left- and right-sided primary lesions confirmed that the difference in survival for patients with different primary tumor sites could be driven by variations in the transforming growth factor ß (TGF-ß), phosphatidylinositol 3-kinase (PI3K) and RAS signaling pathways. Certain genes had a higher variant rate in samples with metachronous CRLM than in samples with simultaneous metastasis. Overall, the metastasis and primary tumor samples displayed highly consistent genomic alterations, but there were some differences between individually paired metastases and primary tumors, which were mainly caused by copy number variations. CONCLUSION: We provide a comprehensive depiction of the genomic alterations in Chinese patients with CRLM, providing a fundamental basis for further personalized therapy applications.

15.
J Leukoc Biol ; 2021 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-34296788

RESUMO

Hemin, a substrate of heme oxygenase (HO)-1, induces HO-1 expression on a variety of cells to exert anti-oxidant and anti-inflammatory roles. However, the role of HO-1 in allergic diseases for dendritic cells (DCs) is not fully understood. Here, we report that HO-1 modulates asthmatic airway inflammation by hemin-treated DC-released extracellular vesicles (DCEVs). Following induction of bone marrow-derived DCs by hemin and then by house dust mite (HDM) in vitro, mouse CD4+ naïve T cells were cocultured with DCEVs to determine T helper (h) cell differentiation. C57BL/6 mice were sensitized by different stimuli-induced DCEVs and challenged with HDM to analyze the changes of inflammatory cells and cytokines in the lung and bronchoalveolar lavage fluid. The results showed that hemin-treated DCEVs (hemin-DCEVs) express phosphatidylserine (PS), CD81, heat shock protein 70, and HO-1, which facilitates regulatory T (Treg) cells differentiation in vitro and in vivo. In HDM-induced asthmatic mouse model, hemin-DCEVs inhalation reduced eosinophils infiltration and mucus secretion in the airway, decreased the levels of IL-4, IL-5, and IL-13 in the lung and the number of Th2 cells in mediastinal lymph nodes (MLNs), and increased the number of Treg cells in MLNs. Thus, our study demonstrated, for the first time, that EVs from HO-1-overexpressing DCs alleviate allergic airway inflammation of eosinophilic asthma by potentiating Treg cells differentiation and limiting proinflammatory cytokine secretion, which expands our understanding of HO-1 function, opening the door for HO-1 inducer-like hemin as a novel therapeutic strategy for asthma or other allergic diseases.

16.
ACS Synth Biol ; 2021 Jul 12.
Artigo em Inglês | MEDLINE | ID: mdl-34251173

RESUMO

Abundant gene clusters of natural products are observed in the endophytic fungus Phomopsis liquidambaris; however, most of them are silent. Herein, a plug-and-play DNA assembly tool has been applied for flavonoid synthesis in P. liquidambaris. A shuttle plasmid was constructed based on S. cerevisiae, E. coli, and P. liquidambaris with screening markers URA, Amp, and hygR, respectively. Each fragment or cassette was successively assembled by overlap extension PCR with at least 40-50 bp homologous arms in S. cerevisiae for generating a new vector. Seven native promoters were screened by the DNA assembly based on the fluorescence intensity of the mCherry reporter gene in P. liquidambaris, and two of them were new promoters. The key enzyme chalcone synthase was the limiting step of the pathway. The naringenin and kaempferol pathways were refactored and activated with the titers of naringenin and kaempferol of 121.53 mg/L and 75.38 mg/L in P. liquidambaris using fed-batch fermentation, respectively. This study will be efficient and helpful for the biosynthesis of secondary metabolites.

17.
Clin Interv Aging ; 16: 1241-1249, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34234424

RESUMO

Objective: Previous studies have explored the association between malnutrition and frailty, but no study has investigated whether the Geriatric Nutritional Risk Index (GNRI), a simple and objective nutritional risk screening tool, is associated with the frailty of older adults. The study aimed to examine the relationship between nutrition-related risk, as assessed by the GNRI, and frailty among older hospitalized patients. Methods: A cross-sectional study was conducted in the West China Hospital of Sichuan University with 740 patients aged ≥70 years between March 2016 and Jan 2017. Nutritional and frailty status was evaluated with the GNRI and FRAIL scale, respectively. The adjusted and unadjusted ordinal logistic regression analyses were used to examine the relationship between nutritional risk and frailty. The ability of GNRI in detecting frailty was assessed by receiver operating characteristic (ROC) curve analysis. Results: The prevalence of low, moderate, and severe nutritional risk among frail patients were 30.1%, 27.6%, and 12.5%, respectively. Ordinal logistic regression analysis showed that malnutrition assessed by the GNRI had a significant association with frailty after adjustment of age, sex, polypharmacy, comorbidity, vision impairment, hearing impairment, cognitive impairment, and depression. In the ROC analysis, the area under the curve for GNRI identifying frailty was 0.698 (95% CI: 0.66-0.74; P<0.001), and the optimal cut-point value was 97.16 (sensitivity: 64.3%; specificity: 66.9%). Conclusion: Nutrition-related risk screened by the GNRI was independently associated with frailty. The GNRI could be used as a simple tool in detecting nutritional risk and frailty status of older patients.


Assuntos
Fragilidade/epidemiologia , Desnutrição/epidemiologia , Estado Nutricional/fisiologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , China , Comorbidade , Estudos Transversais , Feminino , Avaliação Geriátrica/métodos , Hospitalização , Humanos , Masculino , Desnutrição/diagnóstico , Avaliação Nutricional , Prevalência , Curva ROC , Índice de Gravidade de Doença , Fatores Sexuais
18.
Appl Microbiol Biotechnol ; 105(13): 5419-5431, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-34244814

RESUMO

In recent years, an increasing number of studies have shown that fibroblast growth factor 12 (FGF12) plays important roles in regulating neural development and function. Importantly, changes of FGF12 expression are thought to be related to the pathophysiology of many neurological diseases. However, little research has been performed to explore the protective effect of FGF12 on nerve damage. This study aims to explore its neuroprotective effects using our recombinant humanized FGF12 (rhFGF12). The hFGF12 gene was cloned and ligated into an expression vector to construct a recombinant plasmid pET-3a-hFGF12. Single colonies were screened to obtain high expression engineering strains, and fermentation and purification protocols for rhFGF12 were designed and optimized. The biological activities and related mechanisms of rhFGF12 were investigated by MTT assay using NIH3T3 and PC12 cell lines. The in vitro neurotoxicity model of H2O2-induced oxidative injury in PC12 cells was established to explore the protective effects of rhFGF12. The results indicate that the beneficial effects of rhFGF12 were most likely achieved by promoting cell proliferation and reducing apoptosis. Moreover, a transgenic zebrafish (islet) with strong GFP fluorescence in the motor neurons of the hindbrain was used to establish a central injury model caused by mycophenolate mofetil (MMF). The results suggested that rhFGF12 could ameliorate central injury induced by MMF in zebrafish. In conclusion, we have established an efficient method to express and purify active rhFGF12 using an Escherichia coli expression system. Besides, rhFGF12 plays a protective effect of on nerve damage, and it provides a promising therapeutic approach for nerve injury. KEY POINTS: • Effective expression and purification of bioactive rhFGF12 protein in E. coli. • ERK/MAPK pathway is involved in rhFGF12-stimulated proliferation on PC12 cells. • The rhFGF12 has the neuroprotective effects by inhibiting apoptosis.


Assuntos
Fármacos Neuroprotetores , Animais , Escherichia coli/genética , Fatores de Crescimento de Fibroblastos/genética , Humanos , Peróxido de Hidrogênio , Camundongos , Células NIH 3T3 , Fármacos Neuroprotetores/farmacologia , Ratos , Peixe-Zebra
19.
Biomed Res Int ; 2021: 5511290, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34195262

RESUMO

Background: This study is aimed at determining the predictive value of the gray-matter-white-matter ratio (GWR) on brain computed tomography for delayed encephalopathy after acute carbon monoxide (CO) poisoning (DEACMP). Methods: This retrospective cohort study reviewed 352 patients with acute CO poisoning and who underwent the brain computed tomography test. These patients were admitted to Cangzhou Central Hospital from May 2010 to May 2020. The patients were divided into the DEACMP (n = 16) and non-DEACMP (n = 336) groups. Pearson's correlation coefficients were computed for correlation analysis. The predictive value of GWR for DEACMP was evaluated by using logistic regression analysis and receiver operator characteristic curves. Results: The morbidity of DEACMP was 4.5% (16/352). The GWR-basal ganglia, GWR-cerebrum, and GWR-average in the DEACMP group were lower than those in the non-DEACMP group. Correlation analysis indicated that GWR-basal ganglia (r = 0.276; P < 0.001), GWR-cerebrum (r = 0.163; P = 0.002), and GWR-average (r = 0.200; P < 0.001) were correlated with DEACMP. Multivariate logistic regression analysis revealed that reduced GWR-basal ganglia, GWR-cerebrum, and GWR-average were independent risk factors (P < 0.001; P = 0.008; P = 0.001; respectively). Compared with GWR-cerebrum and GWR-average, GWR-basal ganglia had a higher area under the curve of 0.881 (95% confidence interval: 0.783-0.983) with sensitivity and specificity of 93.8% and 68.7%, respectively. The cut-off value of GWR-basal ganglia was 1.055. Conclusion: GWR, especially GWR-basal ganglia, is an early useful predictor for DEACMP.

20.
Metab Brain Dis ; 2021 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-34273043

RESUMO

Diabetes-associated affective disorders are of wide concern, and oxidative stress plays a vital role in the pathological process. This study was to investigate the cerebroprotective effects of hesperetin against anxious and depressive disorders caused by diabetes, exploring the potential mechanisms related to activation of Nrf2/ARE pathway. Streptozotocin-induced diabetic rats were intragastrically administrated with hesperetin (0, 50, and 150 mg/kg) for 10 weeks. Forced swimming test, open field test, and elevated plus maze were used to evaluate the anxiety and depression-like behaviors of rats. The brain was collected for assays of Nrf2/ARE pathway. Moreover, high glucose-cultured SH-SY5Y cells were used to further examine the neuroprotective effects of hesperetin and underlying mechanisms. Hesperetin showed anxiolytic and antidepressant effects in diabetic rats according to the behavior tests, and increased p-Nrf2 in cytoplasm and Nrf2 in nucleus followed by elevations in mRNA levels and protein expression of glyoxalase 1 (Glo-1) and γ-glutamylcysteine synthetase (γ-GCS) in brain, known target genes of Nrf2/ARE signaling. Moreover, hesperetin attenuated high glucose-induced neuronal damages through activation of the classical Nrf2/ARE pathway in SH-SY5Y cells. Further study indicated that PKC inhibition or GSK-3ß activation pretreatment attenuated even abolished the effect of hesperetin on the protein expression of Glo-1 and γ-GCS in high glucose-cultured SH-SY5Y cells. In summary, hesperetin ameliorated diabetes-associated anxiety and depression-like behaviors in rats, which was achieved through activation of the Nrf2/ARE pathway. Furthermore, an increase in nuclear Nrf2 phosphorylation from PKC activation and GSK-3ß inhibition contributed to the activation of Nrf2/ARE pathway by hesperetin.

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