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1.
Food Chem ; 368: 130844, 2022 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-34425338

RESUMO

The sensory perception of food is a dynamic procedure, which is closely related to the released flavor stimuli. Thus, we evaluated the dynamic sensations of fresh and roasted salmon during the chewing process and investigated the tastants released in saliva. For fresh salmon, the fishy, umami, salty, and sweet attributes were perceived successively. Meanwhile, the smoky and fried flavors were the most dominant attributes of roasted salmon at the beginning, then various attributes were perceived. During the chewing process, free amino acids and 5'-nucleotides released in saliva were quantified. Compared to the sensory data, the results demonstrated that glutamic acid and inosine 5'-monophosphate released in saliva might induce the umami perception. The sweet-tasting amino acids alanine and glycine may contribute to sweetness. Therefore, we suggested that the time dimension of tastants dissolved in saliva would affect the dynamic sensation of food, even for complex food materials.


Assuntos
Salmo salar , Animais , Inosina Monofosfato , Mastigação , Sensação , Paladar
2.
Hepatology ; 2021 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-34940991

RESUMO

BACKGROUND AND AIMS: No effective treatments are available for liver fibrosis. Angiogenesis is deeply involved in liver fibrogenesis. However, current controversial results suggest it is difficult to treat liver fibrosis through vascular targeting. There are three different microvessels in liver: portal vessels, liver sinusoids, and central vessels. The changes and roles for each of the three different vessels during liver fibrogenesis are unclear. We propose that they play different roles during liver fibrogenesis, and a single vascular endothelial cell (EC) regulator is not enough to fully regulate these three vessels to treat liver fibrosis. Therefore, a combined regulation of multiple different EC regulatory signaling pathway may provide new strategies for the liver fibrosis therapy. Herein, we present a proof-of-concept strategy by combining the regulation of leukocyte cell-derived chemotaxin 2 (LECT2)/tyrosine kinase with immunoglobulin-like and epidermal growth factor-like domains 1 signaling with that of vascular endothelial growth factor (VEGF)/recombinant VEGF (rVEGF) signaling. APPROACH AND RESULTS: The CCl4 -induced mouse liver fibrosis model and NASH model were both used. During fibrogenesis, vascular changes occurred at very early stage, and different liver vessels showed different changes and played different roles: decreased portal vessels, increased sinusoid capillarization and the increased central vessels the increase of portal vessels alleviates liver fibrosis, the increase of central vessels aggravates liver fibrosis, and the increase of sinusoid capillarization aggravates liver fibrosis. The combinational treatment of adeno-associated viral vector serotype 9 (AAV9)-LECT2-short hairpin RNA (shRNA) and rVEGF showed improved therapeutic effects, but it led to serious side effects. The combination of AAV9-LECT2-shRNA and bevacizumab showed both improved therapeutic effects and decreased side effects. CONCLUSIONS: Liver vascular changes occurred at very early stage of fibrogenesis. Different vessels play different roles in liver fibrosis. The combinational treatment of AAV9-LECT2-shRNA and bevacizumab could significantly improve the therapeutic effects on liver fibrosis.

3.
Int J Ophthalmol ; 14(12): 1820-1827, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926194

RESUMO

AIM: To determine the effect of exosomes derived from human umbilical cord blood mesenchymal stem cells (hUCMSCs) on the expression of vascular endothelial growth factor A (VEGF-A) in human retinal vascular endothelial cells (HRECs). METHODS: Exosomes were isolated from hUCMSCs using cryogenic ultracentrifugation and characterized by transmission electron microscopy, Western blotting and nanoparticle tracking analysis. HRECs were randomly divided into a normal control group (group A), a high glucose model group (group B), a high glucose group with 25 µg/mL (group C), 50 µg/mL (group D), and 100 µg/mL exosomes (group E). Twenty-four hours after coculture, the cell proliferation rate was detected using flow cytometry, and the VEGF-A level was detected using immunofluorescence. After coculture 8, 16, and 24h, the expression levels of VEGF-A in each group were detected using PCR and Western blots. RESULTS: The characteristic morphology (membrane structured vesicles) and size (diameter between 50 and 200 nm) were observed under transmission electron microscopy. The average diameter of 122.7 nm was discovered by nanoparticle tracking analysis (NTA). The exosomal markers CD9, CD63, and HSP70 were strongly detected. The proliferation rate of the cells in group B increased after 24h of coculture. Immunofluorescence analyses revealed that the upregulation of VEGF-A expression in HRECs stimulated by high glucose could be downregulated by cocultured hUCMSC-derived exosomes (F=39.03, P<0.01). The upregulation of VEGF-A protein (group C: F=7.96; group D: F=17.29; group E: F=11.89; 8h: F=9.45; 16h: F=12.86; 24h: F=42.28, P<0.05) and mRNA (group C: F=4.137; group D: F=13.64; group E: F=22.19; 8h: F=7.253; 16h: F=16.98; 24h: F=22.62, P<0.05) in HRECs stimulated by high glucose was downregulated by cocultured hUCMSC-derived exosomes (P<0.05). CONCLUSION: hUCMSC-derived exosomes downregulate VEGF-A expression in HRECs stimulated by high glucose in time and concentration dependent manner.

4.
Front Med (Lausanne) ; 8: 730994, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34957137

RESUMO

Background: With the onset of the coronavirus disease 2019 (COVID-19) pandemic at the beginning of 2020, all non-essential medical treatments were suspended, including fertility treatments. As a unique group in society, patients with infertility may be more sensitive and vulnerable in the face of pressure and crisis. However, to the best of our knowledge, there have been no reports on the influence of postponed fertility treatment on the sexual health of infertile patients owing to COVID-19. Therefore, this study aimed to investigate whether postponed fertility treatment resulting from COVID-19 affects the sexual health of patients with infertility. Methods: A total of 1,442 participants were included for analysis in this large-scale study. Those with postponed fertility treatment were categorised as group A (n = 474), whereas those whose fertility treatment was not delayed were in group B (n = 968). The sexual health and psychological well-being were compared between the two groups. Results: The total Female Sexual Function Index score and five domains of female sexual function (arousal ability, vaginal lubrication, orgasm, satisfaction, and coital pain) were significantly lower in group A than those in group B (p < 0.05). The International Index of Erectile Dysfunction score and Premature Ejaculation Diagnostic Tool score were significantly higher in group A than those in group B (p < 0.05). Conclusions: Delaying fertility treatment obviously affects patients' sexual and mental health. Through a structural equation model, we observed that postponed fertility treatment mediates sexual health by regulating psychological distress and couple relationship quality.

5.
Perioper Med (Lond) ; 10(1): 37, 2021 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-34743734

RESUMO

BACKGROUND: Homocysteine, folate, and vitamin B12 involved in 1-carbon metabolism are associated with cognitive disorders. We sought to investigate the relationships between these factors and delayed neurocognitive recovery (dNCR) after non-cardiac surgery. METHODS: This was a prospective observational study of patients (n = 175) who were ≥ 60 years of age undergoing non-cardiac surgery. Patients were evaluated preoperatively and for 1 week postoperatively by using neuropsychological tests and were divided into dNCR or non-dNCR groups according to a Z-score ≤ - 1.96 on at least two of the tests. The relationship between the occurrence of dNCR and preoperative levels of homocysteine, folate, and vitamin B12 was analyzed. Univariate and multivariable logistic regression analyses were conducted to identify factors associated with dNCR. RESULTS: Delayed neurocognitive recovery was observed in 36 of 175 patients (20.6%; 95% confidence interval [CI], 14.5-26.6%) 1 week postoperatively. Patients who developed dNCR had significantly higher median [interquartile range (IQR)] homocysteine concentrations (12.8 [10.9,14.4] µmol/L vs 10.6 [8.6,14.7] µmol/L; P = 0.02) and lower folate concentrations (5.3 [4.2,7.3] ng/mL vs 6.9 [5.3,9.5] ng/mL; P = 0.01) than those without dNCR. Compared to the lowest tertile, the highest homocysteine tertile predicted dNCR onset (odds ratio [OR], 3.9; 95% CI, 1. 3 to 11.6; P = 0.02), even after adjusting for age, sex, education, and baseline Mini Mental State Examination. CONCLUSIONS: Elderly patients with high homocysteine levels who underwent general anesthesia for non-cardiac surgery have an increased risk of dNCR. This knowledge could potentially assist in the development of preventative and/or therapeutic measures. TRIAL REGISTRATION: NCT03084393 ( https://www.clinicaltrials.gov ).

6.
Front Endocrinol (Lausanne) ; 12: 744628, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721298

RESUMO

Polycystic ovary syndrome (PCOS) is a common endocrine disease accompanied by energetic metabolic imbalance. Because the etiology of PCOS is complex and remains unclear, there is no effective and specific treatment for PCOS. It is often accompanied by various metabolic disorders such as obesity, insulin resistances, and others. Activated brown adipose tissue (BAT) consumes excess energy via thermogenesis, which has positive effects on energy metabolism. Our previous research and that of others indicates that BAT activity is decreased in PCOS patients, and exogenous BAT transplantation can improve PCOS rodents. Notably however, it is difficult to apply this therapeutic strategy in clinical practice. Therapeutic strategies of enhancing endogenous BAT activity and restoring whole-body endocrine homeostasis may be more meaningful for PCOS treatment. In the current study, the dehydroepiandrosterone-induced PCOS rat was exposed to low temperature for 20 days. The results show that cold treatment could reverse acyclicity of the estrous cycle and reduce circulating testosterone and luteinizing hormone in PCOS rats by activating endogenous BAT. It also significantly reduced the expression of steroidogenic enzymes as well as inflammatory factors in the ovaries of PCOS rats. Histological investigations revealed that cold treatment could significantly reduce ovary cystic follicles and increase corpus luteum, indicating that ovulation was recovered to a normal level. Concordant with these results, cold treatment also improved fertility in PCOS rats. Collectively, these findings suggest that cold treatment could be a novel therapeutic strategy for PCOS.

7.
PeerJ ; 9: e12162, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34721957

RESUMO

Background: To date, there have been no reports on the sexual and psychological health of patients with azoospermia during the coronavirus disease 2019 (COVID-19) pandemic. Previous studies on the sexual health of couples with azoospermia are limited and are especially lacking in data on the wives of azoospermic men. Methods: We conducted a case-control cross-sectional study between 1 July 2020 and 20 December 2020. In total, 100 couples with azoospermia comprised the experimental group and 100 couples with normozoospermia comprised the control group. The couples' sexual health was measured using standardised sexual function questionnaires (male: International Index of Erectile Function-15 [IIEF-15] and Premature Ejaculation Diagnostic Tool [PEDT]; female: Female Sexual Function Index [FSFI]) and a self-designed questionnaire to evaluate changes in sexual behaviours (sexual satisfaction, desire, frequency of sexual activity, masturbation, and pornography use) during lockdown. The couples' psychological health was measured using the 7-item Generalized Anxiety Disorder (GAD-7) scale and 9-item Patient Health Questionnaire (PHQ-9). The Actor-Partner Interdependence Model (APIM) was used to analyse the associations between sexual health and psychological health. Results: The IIEF-15 scores (53.07 ± 11.11 vs. 57.52 ± 8.57, t =  - 3.17, p = 0.00) were lower and the PEDT scores (6.58 ± 3.13 vs. 5.17 ± 2.22, t = 3.67, p = 0.00) and incidence of premature ejaculation (χ 2 = 14.73, p = 0.00) were higher for men with azoospermia than for men with normozoospermia. Compared with those of wives of men with normozoospermia, the total FSFI scores (25.12 ± 5.56 vs. 26.75 ± 4.82, t =  - 2.22, p = 0.03) of wives of men with azoospermia were lower. The chi-square test showed that the perceived changes in sexual satisfaction (χ 2 = 7.22, p = 0.03), frequency of masturbation (χ 2 = 21.96, p = 0.00), and pornography use (χ 2 = 10.90, p = 0.01) were significantly different between the female groups with azoospermia and normozoospermia, but there were no significant changes in sexual behaviour between the male groups. The GAD-7 (men: 7.18 ± 5.56 vs. 5.68 ± 4.58, p = 0.04; women: 6.65 ± 5.06 vs. 5.10 ± 3.29, p = 0.01) and PHQ-9 scores (men: 10.21 ± 6.37 vs. 7.49 ± 6.10, p = 0.00; women: 8.81 ± 6.50 vs. 6.98 ± 4.43, p = 0.02) were significantly higher for couples with azoospermia than for couples with normozoospermia. The APIM showed that for couples with azoospermia, sexual function negatively correlated with their own anxiety (men: ß = -0.22, p = 0.00; women: ß = -0.38, p = 0.00) and depression symptoms (men: ß = -0.21, p = 0.00; women: ß = -0.57, p = 0.00) but not with their partner's anxiety and depression symptoms (p > 0.05). Conclusions: Couples with azoospermia had a lower quality of sexual function and higher levels of psychological distress than couples with normozoospermia. Their sexual health negatively correlated with psychological distress.

8.
Int J Biol Macromol ; 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34822828

RESUMO

TGFß1 signaling pathway is associated with many diseases, which can induce the activation of hepatic stellate cells (HSCs) and induce liver fibrosis. Studies have shown that 20S-protopanaxadiol (PPD) has a therapeutic effect on liver fibrosis, but the target is unknown. In this study, we confirmed that PPD reduced the mRNA expression of downstream genes of the TGFß1 pathway, which suggesting PPD is associated with the TGFß1 pathway. The protein dissociation temperature and dissociation constant (Kd) of PPD on TGFßR1 and TGFßR2 were determined, which showed that PPD combined with TGFßR1 (Kd = 1.54 µM). The docking and simulation methods were used to find their binding sites. Site mutations, protein expression and in vitro binding experiments were performed to demonstrated these sites. In particular, these sites of TGFßR1 were also the active sites of TGFßR2. Therefore, we speculated that PPD blocked the combination of TGFßR1 and TGFßR2 by binding to the D57, R58, P59, and N78 of the TGFßR1 extracellular domain. Thus, PPD could block the transmission of TGFß1 pathway and inhibit the activation of HSCs, and treating fibrosis. Our studies showed that PPD has the potential to treat diseases related to the TGFß1 pathway and broadens its clinical application.

9.
Nanoscale ; 13(45): 19004-19011, 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34755160

RESUMO

Magnetic iron oxide nanoparticles have been proven to have versatile applications in biomedicine. Although numerous strategies have been developed to synthesize hydrophilic magnetic nanoparticles, there is still a challenge in the quantity and controllability of preparation of highly dispersible, stably water-dispersive magnetic nanoparticles. The current work presents a deep-eutectic solvent electrolysis to synthesize magnetic nanoparticles. In the electrolysis process, iron atoms at the anode electrode are oxidized to ferric ions, and then the ferric ions are combined with reactive oxygen species that derived from the decomposition of deep-eutectic solvents to form iron oxide nanocrystals. Concomitantly, hydrophilic radicals of amine groups produced by electrolyte decomposition are grafted on the particles. The monodisperse nanoparticle size ranged from 6 to 9 nm. The hydrophilic group loaded nanoparticles can be highly dispersed in water with neither surface post-modification nor organic stabilizers. The hydrodynamic particle diameter is between 20 and 30 nm. The transparent aqueous dispersions can be maintained for more than 600 days without precipitation.

10.
BMC Infect Dis ; 21(1): 1156, 2021 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-34775956

RESUMO

BACKGROUND: Streptococcus pneumoniae (S. pneumoniae) is a major cause of bacterial meningitis, septicemia and pneumonia in children. Inappropriate choice of antibiotic can have important adverse consequences for both the individual and the community. Here, we focused on penicillin/cefotaxime non-susceptibility of S. pneumoniae and evaluated appropriateness of targeted antibiotic therapy for children with IPD (invasive pneumococcal diseases) in China. METHODS: A multicenter retrospective study was conducted in 14 hospitals from 13 provinces in China. Antibiotics prescription, clinical features and resistance patterns of IPD cases from January 2012 to December 2017 were collected. Appropriateness of targeted antibiotics therapy was assessed. RESULTS: 806 IPD cases were collected. The non-susceptibility rates of S. pneumoniae to penicillin and cefotaxime were 40.9% and 20.7% respectively in 492 non-meningitis cases, whereas those were 73.2% and 43.0% respectively in 314 meningitis cases. Carbapenems were used in 21.3% of non-meningitis cases and 42.0% of meningitis cases for targeted therapy. For 390 non-meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were used in 17.9% and 8.7% of cases respectively for targeted therapy. For 179 meningitis cases with isolates susceptible to cefotaxime, vancomycin and linezolid were prescribed in 55.3% and 15.6% of cases respectively. Overall, inappropriate targeted therapies were identified in 361 (44.8%) of 806 IPD cases, including 232 (28.8%) cases with inappropriate use of carbapenems, 169 (21.0%) cases with inappropriate use of vancomycin and 62 (7.7%) cases with inappropriate use of linezolid. CONCLUSIONS: Antibiotic regimens for IPD definite therapy were often excessive with extensive prescription of carbapenems, vancomycin or linezolid in China. Antimicrobial stewardship programs should be implemented to improve antimicrobial use.


Assuntos
Antibacterianos , Infecções Pneumocócicas , Antibacterianos/uso terapêutico , Criança , China/epidemiologia , Humanos , Lactente , Testes de Sensibilidade Microbiana , Infecções Pneumocócicas/tratamento farmacológico , Infecções Pneumocócicas/epidemiologia , Prescrições , Estudos Retrospectivos
11.
Cancer Biol Med ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34633776

RESUMO

OBJECTIVE: This study aimed to evaluate the safety, efficacy, and feasibility of the rituximab, fotemustine, pemetrexed, and dexamethasone (R-FPD) regimen followed by whole-brain radiotherapy (WBRT) for patients with primary central nervous system lymphoma (PCNSL). METHODS: A prospective, single-center phase II clinical trial was conducted. Patients with PCNSL newly diagnosed at the First Affiliated Hospital of Zhengzhou University between July 2018 and July 2020 were studied. The R-FPD regimen consisted of rituximab (375 mg/m2 i.v. on D0), fotemustine (100 mg/m2 i.v. on D1), pemetrexed (600 mg/m2 i.v. on D1), and dexamethasone (40 mg i.v. on D1-5). Patients 60 years or younger who showed a complete response (CR) were treated with 23.4 Gy of WBRT after the end of chemotherapy; those older than 60 years with CR were treated with a wait-and-see approach; and those who did not show CR after the 4th cycle of chemotherapy were given salvage WBRT 30 Gy + local tumor field irradiation up to 45 Gy, regardless of age. RESULTS: A total of 30 patients were included. After 2 cycles, the objective response rate (ORR) was 96.5% (28/29, 1 CR, 27 PR, 0 SD, and 1 PD). After 4 cycles, the ORR was 73.1% (19/26, 11 CR, 8 PR, 4 SD, and 3 PD). After WBRT, the ORR was 90.9% (10/11, 7 CR, 3 PR, and 1 SD). The grade III and IV toxicity responses were mainly leukopenia (20.0%), thrombocytopenia (23.3%), and anemia (10.0%). CONCLUSIONS: Fotemustine-based therapy in combination with rituximab chemotherapy followed by WBRT can improve outcomes, providing ORR benefits and favorable tolerability in patients newly diagnosed with PCNSL.

12.
Reprod Biol Endocrinol ; 19(1): 157, 2021 Oct 09.
Artigo em Inglês | MEDLINE | ID: mdl-34627263

RESUMO

BACKGROUND: Infertility, an important source of stress, could affect sexual life. Extensive studies suggest that the incidence of sexual dysfunction is highly prevalent in infertile women. As the duration of infertility increases, the level of stress is also likely to increase even further, and this could aggravate psychological pain and cause sexual dysfunction. However, the effect of infertility duration on sexual health is unclear. METHODS: We conducted a case-control study in which 715 patients participated between September 1,2020 and December 25, 2020. We included patients diagnosed with infertility (aged between 20 to 45), who were divided into four groups according to their infertility durations: ≤ 2 years (Group I, n = 262), > 2 years but ≤ 5 years (Group II, n = 282), > 5 years but ≤ 8 years (Group III, n = 97), and > 8 years (Group IV, n = 74). A questionnaire survey on female sexual functions and psychological depression was administered to participants, and their female sexual functions and depression status were measured using the Female Sexual Function Index (FSFI) and Patient Health Questionnaire (PHQ-9), respectively. RESULTS: As the number of years of infertility increased, the PHQ-9 score as well as the incidence of psychological depression increased significantly (p < 0.05), but the total score of FSFI and those of its six domains/sub-scales were not significantly different among the four groups. An analysis of the relevant factors affecting sexual functions, using the multivariable logistic regression model, revealed that when the infertility duration was greater than 8 years, there was a significant increase in the incidence of sexual dysfunction [adjusted odds ratios (AOR) = 5.158, 95% confidence interval (CI): 1.935-13.746, P = 0.001], arousal disorder (AOR = 2.955, 95% CI: 1.194-7.314, P = 0.019), coital pain (AOR = 3.811, 95% CI: 1.045-13.897, P = 0.043), and lubrication disorder (AOR = 5.077, 95% CI: 1.340-19.244, P = 0.017). CONCLUSIONS: An increasing infertility duration is a risk factor for the occurrence of sexual dysfunction. Hence, as the infertility duration increases, the incidence of female sexual dysfunction and psychological distress could also increase, especially when the infertility duration is more than 8 years.

13.
Adv Sci (Weinh) ; 8(21): e2101991, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34514733

RESUMO

Intermittent fasting (IF), as a dietary intervention for weight loss, takes effects primarily through increasing energy expenditure. However, whether inter-organ systems play a key role in IF remains unclear. Here, a novel hepatokine, pregnancy zone protein (PZP) is identified, which has significant induction during the refeeding stage of IF. Further, loss of function studies and protein therapeutic experiment in mice revealed that PZP promotes diet-induced thermogenesis through activating brown adipose tissue (BAT). Mechanistically, circulating PZP can bind to cell surface glucose-regulated protein of 78 kDa (GRP78) to promote uncoupling protein 1 (UCP1) expression via a p38 MAPK-ATF2 signaling pathway in BAT. These studies illuminate a systemic regulation in which the IF promotes BAT thermogenesis through the endocrinal system and provide a novel potential target for treating obesity and related disorders.

14.
Expert Rev Neurother ; 21(10): 1179-1189, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34538154

RESUMO

INTRODUCTION: Although experimental data suggest that Selective serotonin reuptake inhibitors (SSRIs) may improve motor recovery after stroke, the results from clinical studies are conflicting. AREAS COVERED: Six international electronic databases (Cochrane, PubMed, Embase, Web of Science, CINAHL, and PsycINFO) and four Chinese electronic databases (CBM, CNKI, WanFang Data, and VIP) were systematically searched up to April 2021. Co-primary outcomes were motor function and tolerability. Secondary outcomes included disability, neurological function, continuous depression scores, and adverse events. RESULTS: 25 randomized controlled trials including 4777 participants were identified. Pooled analyses found SSRIs significantly improved motor function [standardized mean differences (SMD), 0.72; 95% CI, 0.46 to 0.99], disability (SMD, 0.79; 95% CI, 0.51 to 1.06), neurological function (SMD, -0.58; 95% CI, -0.77 to -0.39) and continuous depression scores (SMD, -0.36; 95% CI, -0.70 to -0.02). SSRIs were associated with increased seizure (risk ratio, 9.00; 95% CI, 1.69 to 47.91) and gastrointestinal side effects (risk ratio, 2.26; 95% CI, 1.56 to 3.28), but similar risk of all-cause discontinuations when compared with the control group (risk ratio, 1.11; 95% CI, 0.79 to 1.56). EXPERT OPINION: SSRIs are effective and well-tolerated to promote motor recovery after stroke, but may increase the risk of seizures and gastrointestinal adverse effects.

15.
J Cancer ; 12(19): 5760-5771, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34475990

RESUMO

S100 calcium binding protein A1 (S100A1) is an important member of the S100 family and known to express in a variety of cancers. However, the biological functions of S100A1 in thyroid carcinoma have not been thoroughly studied. In this report, bioinformatics analyses and immunohistochemistry assays were applied to assess the expression profile of S100A1 as well as its relationship with the pathological features and prognosis of papillary thyroid carcinoma (PTC). Meanwhile, functions of S100A1 in PTC cells were analyzed with either in vitro or in vivo experiments. S100A1 was significantly up-regulated in PTC tissues compared with adjacent non-cancerous tissues. S100A1 protein expression was significantly associated with tumor size (p=0.0032) or lymph node metastasis (p=0.0331). More importantly, an elevated S100A1 expression was significantly correlated with a worse recurrence-free survival (RFS) (HR=2.26, p=0.042). Further, knockdown of S100A1 dramatically inhibited cell proliferation and migration as well as increased apoptosis of PTC cells. S100A1 knockdown inhibited tumor progression as seen in in vivo experiments. In terms of mechanism, down-regulation of S100A1 induced yes associated protein (YAP) phosphorylation in the cytoplasm and diminished Hippo/YAP pathway activation. Therefore, S100A1 may serve as a novel oncogene and a promising biomarker for PTC diagnosis and prognosis.

16.
Insects ; 12(9)2021 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-34564276

RESUMO

The brown planthopper (BPH) is one of the main pests endangering rice yields. The development of rice varieties harboring resistance genes is the most economical and effective method of managing BPH. To identify new BPH resistance-related genes, a total of 123 rice varieties were assessed for resistance and durable resistance. Three varieties were immune, and nine were highly resistant to BPH. After whole-genome resequencing of all 123 varieties, 1,897,845 single nucleotide polymorphisms (SNPs) were identified. Linkage disequilibrium (LD) decay analysis showed that the average LD of the SNPs at 20 kb was 0.30 (r2) and attenuated to half value (~0.30) at a distance of about 233 kb. A genome-wide association study (GWAS) of durable resistance to BPH was conducted using the Fast-MLM model. One quantitative trait locus, identified on chromosome 2, included 13 candidate genes. Two candidate genes contained a leucine-rich repeat and CC-NBS-LRR or NB-ARC domains, which might confer resistance to pests or diseases. Interestingly, LOC_Os02g27540 was highly expressed and was induced by BPH; GWAS identified potential rice genes coding for durable resistance to BPH. This study helps to elucidate the mechanism of durable resistance to BPH in rice and provides essential genetic information for breeding and functional verification of resistant varieties.

17.
Sci Total Environ ; 799: 149444, 2021 Dec 10.
Artigo em Inglês | MEDLINE | ID: mdl-34365263

RESUMO

To date, dermal/hand-to-mouth exposure to chemicals in the e-waste recycling environment has not been sufficiently understood, and the importance of dermal absorption of chemicals in e-waste dismantling workers remains controversial. In this study, we utilized hand wipes and matched sera to characterize dermal/hand-to-mouth exposure to PCBs for e-waste dismantling workers, and potential effects on thyroid hormones were also assessed. PCB loadings in hand wipes varied from 0.829-265 ng wipe-1 (11.3-2850 ng m-2 wipe-1), with 37.2 ng wipe-1 (432 ng m-2 wipe-1) as the median value. Serum concentrations of PCBs ranged from 32.3-3410 ng g-1 lipid weight (lw) with 364 ng g-1 lw as the median value. Between wipes and sera, lower-chlorinated congeners (e.g. CB-28, -66, -74, -99,-105 and -118) showed significant associations (p < 0.01), but higher-chlorinated congeners (e.g. CB-138, -153, -156, -170, and -180) did not. These lower-chlorinated CBs were the major contributors to estimated dermal/hand-to-mouth average daily doses (ADDs) and the hazard index (HI). Correspondingly, their estimated contributions to serum levels by dermal absorption were also significant, with the contribution of CB-28 being as high as 21.4%. As a consequence, dermal absorption of some low-chlorinated congeners was a non-negligible route for e-waste dismantling workers. Although insignificant association was shown between serum PCBs and thyroid hormones, the potential health risk should be of concern due to the high levels of PCBs observed in workers' sera.


Assuntos
Resíduo Eletrônico , Poluentes Ambientais , Bifenilos Policlorados , China , Resíduo Eletrônico/análise , Poluentes Ambientais/análise , Humanos , Bifenilos Policlorados/análise , Reciclagem
18.
Exp Ther Med ; 22(3): 991, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34345273

RESUMO

Obeticholic acid (OCA) is exemplified as a potent drug for treating primary biliary cirrhosis and nonalcoholic fatty liver disease by inhibiting bile acid synthesis. However, it remains unclear whether the effect of OCA is mediated by the function of brown adipose tissue (BAT). In the present study, brown adipogenesis differentiation in vitro and db/db mouse model treated with OCA were used to assess the anti-obesity function by body weight tracking, O2 consumption, food intake, physical activity, glucose tolerance tests. In addition, uncoupling protein 1 (Ucp1) protein expression in brown adipose tissue was measured by western blotting, morphometry of brown adipose tissue was analyzed by hematoxylin and eosin staining. Hepatic steatosis was detected by Oil-Red O staining and serological analysis was performed to assess the effect of OCA on hyperlipidemia. OCA treatment enhanced brown adipocyte cell differentiation and upregulated the expression of the BAT-specific gene Ucp1) in C3H10T1/2 cells in vitro. Consistent with these findings, OCA increased whole-body energy metabolism and glucose homeostasis by enhancing BAT activity in vivo, and ultimately decreased body weight gain in db/db mice. In addition, the results demonstrated that spontaneous hepatic steatosis in db/db mice was ameliorated following OCA treatment. In summary, OCA functioned as a BAT activator to help ameliorate obesity and maintain glucose homeostasis in db/db mice. The present results may provide a novel potential therapeutic approach to activate brown fat in patients with obesity and other metabolic disorders.

19.
Appl Microbiol Biotechnol ; 105(14-15): 6007-6018, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34390354

RESUMO

Liver fibrosis is caused by the accumulation of extracellular matrix proteins on the surface of hepatocytes and results from chronic liver injury. TGFß1 is one of the most important promoters of hepatic fibrosis, which accelerates the transformation of hepatic stellate cells to myofibroblasts and collagen expression. It is well-known that TGFß1 binds to TGFßR2 to mediate its downstream signal cascades to regulate target gene transcription. Therefore, the TGFßR2 blocker might be a prominent drug candidate. We constructed TGFßR2 extracellular domain into living biotherapeutics Lactococcus lactis to reduce hepatic fibrosis in CCl4 treated mice in the present study. We found that the culture supernatant of the recombinant bacteria can inhibit the TGFß1-induced collagen synthesis in the hepatic stellate cells at the cellular level. In addition, results of in vivo study showed that the recombinant bacteria significantly reduced the degree of liver fibrosis in CCl4-treated mice. Furthermore, flow cytometry results indicated that the recombinant bacteria treatment significantly reduced the CD11b+ Kupffer cells compared with the empty vector bacteria group. Consistently, fibrosis-related gene and protein expression were significantly reduced upon recombinant bacteria treatment. Finally, the subchronic toxicity test results showed that this bacteria strain did not have any significant side effects. In conclusion, our recombinant Lactococcus lactis shows tremendous therapeutic potential in liver fibrosis. KEY POINTS: • The supernatant of L. lactis expressing TGFßR2 inhibits the activation of myofibroblast. • The oral recombinant strain reduced the degree of liver fibrosis and inflammation in mice. • The recombinant strain was safe in subchronic toxicity test in mice.


Assuntos
Lactococcus lactis , Animais , Colágeno , Hepatócitos , Lactococcus lactis/genética , Cirrose Hepática/prevenção & controle , Camundongos
20.
Exp Cell Res ; 407(1): 112790, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-34418460

RESUMO

BACKGROUND: Natural killer/T cell lymphoma (NKTCL) is a distinct subtype of Non-Hodgkin's lymphoma with highly aggressive clinical behavior. We aim to investigate the function of Latent transforming growth factor ß binding protein 1 (LTBP1) and transforming growth factor beta1 (TGF-ß1) and complex molecular pathogenesis of this disease. METHODS: NKTCL patients and reactive lymph nodes patients were recruited in this study. The expression of LTBP1 and TGF-ß1 was examined using qRT-PCR, Western blot, IHC and ELISA analyses in biopsied tissues and serum from participants and NKTCL cell lines. Cell proliferation was determined using CFSE. Cell cycle and apoptosis were evaluated using flow cytometric analyses. The expression of Ki-67, CDK4 and cyclinD1 proteins was measured using Western blot analyses. The roles of LTBP-1/TGF-ß1 in EMT program were determined by measuring E-cadherin, N-cadherin and Vimentin using Western blot analyses. The effects of LTBP-1 and TGF-ß1 on tumor progression in vivo were determined by animal experiments. RESULTS: LTBP-1 and TGF-ß1 levels were elevated in NKTCL tissues and serum. The expression of LTBP-1 was positively correlated with the expression of TGF-ß1 in NKTCL tissues. LTBP-1 was overexpressed in NKTCL cells. Knockdown of LTBP-1 suppressed cell proliferation and cell cycle progression, induced cell apoptosis, and suppressed EMT program in NKTCL cells. These effects of LTBP-1 knockdown were attenuated after TGF-ß1 stimulation. Knockdown of LTBP-1 inhibited NKTCL tumor weight and volume in vivo. Also, stimulation of TGF-ß1 attenuated the suppressive effects on tumor growth from sh-LTBP-1. Silencing of LTBP-1 lowered cellular TGF-ß1, phosphorylated-Smad2, phosphorlyatd-Smad3, and phosphorylated-p38 and the suppressive effects were reversed after stimulation of TGF-ß1. CONCLUSION: Our findings suggested that inhibition of LTBP-1/TGF-ß1 suppressed the malignant phenotypes of NKTCL cells and tumor growth via inactivating the canonical TGF-ß/Smad signaling and p38MAPK signaling.


Assuntos
Células Matadoras Naturais/metabolismo , Proteínas de Ligação a TGF-beta Latente/metabolismo , Linfoma de Células T/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Humanos , Transdução de Sinais/efeitos dos fármacos , Vimentina/metabolismo
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