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1.
Bioengineered ; 12(1): 3125-3136, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34193023

RESUMO

Ultraviolet B (UVB) is one of the most common exogenous factors in skin aging, especially photoaging. Once a large amount of UVB accumulates within a short period of time, skin tissue can become inflamed. It has also been found in clinics that platelet-rich plasma (PRP) can promote wound repair; therefore, the aim of this study was to identify the mechanism by which PRP repairs UVB-induced skin photodamage. We used PRP of Sprague-Dawley rats with the two-spin technique in the established acute UVB radiation photodamage model and harvested the corresponding skin after 1, 7, and 28 d. Hematoxylin and eosin staining was used to observe tissue inflammation. We found that PRP reduces inflammation in the early stages of UVB-induced acute skin damage, and then promotes the proliferation of collagen in the middle and late stages. Moreover, PRP can stimulate Act A and M1 polarization in the early stage, while inhibiting activin A (Act A) and inducing M2 polarization in the middle and late stages. In conclusion, this study demonstrates that PRP plays an important regulatory role in helping reduce UVB-induced acute skin tissue inflammation by adjusting macrophage polarization, which alleviates skin inflammation and stimulates collagen regeneration.

3.
Andrologia ; : e14169, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34197007

RESUMO

The blood-testis barrier (BTB) of Sertoli cells (SCs) is an important biological barrier that maintains spermatogenesis and provides a favourable microenvironment for spermatogenesis. However, heat stress can directly damage the BTB structural proteins of testicular SCs, leading to dyszoospermia. Wuzi Yanzong Pills (WYP) is a traditional Chinese medicine formula used to treat male reproductive diseases. However, whether WYP could ameliorate heat stress injury in primary SCs extracted from rat testes and BTB proteins remains unknown. Here, treatment with WYP (low, medium and high dose) increased the SC viability and the proliferation of cell antigen Ki67 significantly. Additionally, it promoted SC maturation, which presented in the form of increased androgen receptors (ARs) and decreased cytokeratin 18 (CK-18) in three WYP dose groups. WYP upregulated BTB proteins such as zonula occludens 1 (ZO-1) and occludin across all WYP groups and decreased phosphorylated Akt (p-Akt) in the middle and high-dose groups; however, ZO-1 and occludin recovery were reduced with the presence of Akt inhibitor in WYP groups. WYP improved SC viability and proliferation, and ameliorated dedifferentiation and BTB-proteins damaged by heat stress via Akt signalling. The findings present theoretical support for the effects of WYP in the management of dyszoospermia and male infertility.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34314077

RESUMO

There is a continuous need for novel microbial natural products to fill the drying-up drug development pipeline. Herein, we report myxadazoles from Myxococcus sp. SDU36, a family of novel chimeric small molecules that consist of N-ribityl 5,6-dimethylbenzimidazole and a linear fatty acid chain endowed with an isoxazole ring. The experiments of genome sequencing, gene insertion mutation, isotope labelling, and precursor feeding demonstrated that the fatty acid chain was encoded by a non-canonical PKS/NRPS gene cluster, whereas the origin of N-ribityl 5,6-dimethylbenzimidazole was related to the vitamin B12 metabolism. The convergence of these two distinct biosynthetic pathways through a C-N coupling led to the unique chemical framework of myxadazoles, which is an unprecedented hybridization mode in the paradigm of natural products. Myxadazoles exhibited potent vasculogenesis promotion effect and moderate antithrombotic activity, underscoring their potential usage for the treatment of cardiovascular diseases.

5.
Plant Physiol Biochem ; 166: 849-856, 2021 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-34229165

RESUMO

γ-Aminobutyric acid (GABA), a signal molecule, is regarded as the intersection node of carbon and nitrogen metabolism, and its contributions to flavonoid metabolism in tea plant growth and development remain unclear. The correlation between the GABA shunt and flavonoid metabolism in tea plants is worth to explore. Secondary metabolites and their correlations with the taste of tea soup made from tea plants (Camellia sinensis) during different seasons were investigated. Related secondary metabolites and transcript profiles of genes encoding enzymes in the GABA shunt, flavonoid pathway and polyamine biosynthesis were measured throughout the tea plant growth seasons and after exogenous GABA applications. In addition, the abundance of differentially expressed proteins was quantified after treatments with or without exogenous GABA. The tea leaves showed the highest metabolite concentrations in spring season. CsGAD, CsGABAT, CsSPMS, CsODC, CsF3H and CsCHS were found to be important genes in the GABA and anthocyanin biosynthesis pathways. GABA and anthocyanin concentrations showed a positive correlation, to some extent, CsF3H and CsCHS played important roles in the GABA and anthocyanin biosynthesis.

6.
Front Immunol ; 12: 624753, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34239515

RESUMO

The pathological mechanism underlying heat stroke (HS) is associated with the dysbalanced inflammation and coagulation cascade. Cell-derived circulating extracellular vesicles (EVs), as a novel pathway mediating intercellular communication, are associated with the immune response and inflammation in critical inflammatory syndromes, such as sepsis. Although these vesicles contain genetic material correlated with their biological function, their molecular cargo during HS remains unknown. In this study, we evaluate the presence of microRNAs (miRNAs) and messenger RNAs (mRNAs) associated with inflammatory responses and coagulation cascade in exosomes of patients with HS. Blood samples were collected from three patients with HS at the time of admission to the intensive care unit; three healthy volunteers were selected as control. Exosomes were isolated using ultracentrifugation, and their miRNA content was profiled using next-generation sequencing; mRNA content was evaluated using qPCR array. Compared with those from healthy volunteers, exosomes from patients with HS showed substantial changes in the expression of 202 exosomal miRNAs (154 upregulated and 48 downregulated miRNAs). The most upregulated miRNAs included miR-511-3p, miR-122-5p, miR-155-3p, miR-1290, and let7-5p, whereas the most downregulated ones included miR-150-3p, 146a-5p, and 151a-3p. Gene ontology enrichment of the miRNAs of patients with HS compared with control subjects were associated mostly with inflammatory response, including T cell activation, B cell receptor signaling, dendritic cell chemotaxis and leukocyte migration, and platelet activation and blood coagulation. The identified miRNAs were primarily enriched to the signal transduction pathways namely, T cell receptor signaling, Ras signaling, chemokine signaling, platelet activation, and leukocyte transendothelial migration, all of which are associated with inflammation and hemostasis. Multiple targeted mRNAs associated with the inflammatory response, blood coagulation, and platelet activation were further verified in serum exosomes. Exosomes from patients with HS convey miRNAs and mRNAs associated with pathogenic pathways, including inflammatory response and coagulation cascade. Exosomes may represent a novel mechanism for intercellular communication during HS.

7.
Free Radic Biol Med ; 2021 Jul 22.
Artigo em Inglês | MEDLINE | ID: mdl-34303830

RESUMO

BACKGROUND: Congenital hereditary endothelial dystrophy (CHED) is a rare genetic disease of the corneal endothelium with a very early onset of bilateral corneal edema due to degeneration and dysfunction of the corneal endothelium. Currently SLC4A11 is the only established causative gene for CHED, but not all these reported CHED patients could be explained by SLC4A11 deficiency, indicating that the genetic predisposition of CHED still requires further exploration. METHODS: Trio-based whole-exome sequencing was performed on a CHED patient and his unaffected parents. The GATK2 and an in-house bioinformatics pipeline were applied for variant analyses, following the 2015 American College of Medical Genetics and Genomics (ACMG) guidelines. Potential pathogenic variants were further validated by Sanger sequencing. The expression profiles of FAM149A in cell line, murine tissues or human corneal endothelia were determined by RT-qPCR. Small interfering RNA was used to knock down the expression of FAM149A in vitro. Cell viability was detected by a CCK-8 assay. ROS and 8-OHdG were examined by fluorometric analysis. The nuclear translocation of NRF2 was determined by western blotting. RESULTS: We identified a homozygous mutation (NM_015398.3: c.991A > G; p.R331G) in the FAM149A gene that related to the phenotype of CHED. FAM149A was found to be highly expressed in corneal endothelium, and up-regulated upon oxidative stress. Further functional investigations demonstrated that deficiency in FAM149A impaired Nrf2-antioxidant signaling, rendering cells more vulnerable to oxidative stress. Consistently, the expression of FAM149A was significantly reduced in patients with corneal endothelium dysfunction. CONCLUSION: This study demonstrated, for the first time, FAM149A as a plausible causative gene for CHED etiology, offering new insight for future investigation targeting CHED.

8.
Artigo em Inglês | MEDLINE | ID: mdl-34291539

RESUMO

N 6 -methyladenosine (m 6 A) modification - the most prevalent mammalian RNA internal modification - plays key regulatory roles in mRNA metabolism. Current approaches for m 6 A modified RNA analysis limit at bulk-population level, resulting in a loss of spatiotemporal and cell-to-cell variability information. Here we proposed a m 6 A-specific in situ hybridization mediated proximity ligation assay (m 6 AISH-PLA) for cellular imaging of m 6 A RNA, allowing to identify m 6 A modification at specific location in RNAs and image m 6 A RNA with single-cell and single-molecule resolution. Using m 6 AISH-PLA, we investigated the m 6 A level and subcellular location of HSP70 RNA103-m 6 A in each cell in response to heat shock, and found an increased m 6 A modified ratio and an increased distribution ratio in cytoplasm under heat shock stress. m 6 AISH-PLA can serve in the study of m 6 A RNA in single-cell for deciphering epitranscriptomic mechanisms and assisting clinical diagnosis.

9.
J Hazard Mater ; 420: 126550, 2021 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-34252664

RESUMO

The critical health risks caused by cadmium (Cd) via dietary exposure are commonly assessed by detecting Cd concentrations in foods. Differently, in this study, the bioaccessibility and bioavailability of Cd in major local harvests were introduced to assess the dietary exposure of local residents from a high-level environmental Cd region. The results indicated that certain Cd was released into the digestive juice after in vitro digestion with a bioaccessibility of 20-63% for rice and 3-32% for leafy vegetables, and the released portion was partially absorbed by Caco-2 cells with a bioavailability of 2-21% for rice and 0.2-13% for leafy vegetables. The results obtained from the toxicokinetic model revealed that the predicted urinary Cd values from the estimated daily intake (EDI) of Cd, which accounted for bioaccessibility and bioavailability, were consistent with the actual measured values, and the EDIs were considerably lower than the acceptable daily intake. This suggests that the bioaccessibility and bioavailability adjusted dietary Cd exposure should be more precise. The key issues addressed in our study implores that a potential health risk cannot be neglected in people with high consumption of rice from high-level zone.

10.
Front Immunol ; 12: 674808, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34248956

RESUMO

Background: NOD-like receptor family CARD-containing 4 protein (NLRC4) is a cytosolic protein that forms an inflammasome in response to flagellin and type 3 secretion system (T3SS) proteins from invading Gram-negative bacteria. NLRC4 mutations have been recently identified in early-onset severe autoinflammatory disorders. In this study, we reported a novel mutation in NLRC4 in two Chinese patients, who manifested with recurrent urticaria and arthralgia. Methods: We summarized the clinical data of the two patients. Gene mutations were identified by whole-exome sequencing (WES). Swiss-PdbViewer was used to predict the pathogenicity of the identified mutations. Cytokine levels and caspase-1 activation were detected in the patient PBMCs with lipopolysaccharide (LPS) stimulation. All previously published cases with NLRC4 mutations were reviewed. Results: We identified a missense heterozygous mutation (c.514G>A, p.Gly172Ser), which was located in the highly conserved residue of nucleotide-binding domain (NBD) of NLRC4. The mutation did not alter the expression of NLRC4 protein, but induced considerably much higher production of IL-1ß and IL-6 in patient PBMCs than in healthy controls after LPS stimulation. Four NLRC4 inflammasomopathy phenotypes have been described, with severe inflammatory diseases including macrophage activation syndrome, enterocolitis and NOMID in patients with mutations in the NBD and HD1 domains, whereas a mild clinical phenotype was associated with two mutations in the WHD domain of NLRC4. Conclusion: We identified a novel mutation in the NBD domain, and the patients just presented with a mild inflammatory phenotype. Thus, our findings reinforce the diversity of NLRC4 mutations and expand the clinical spectrum of associated diseases.

11.
Sci Total Environ ; 795: 148886, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-34247077

RESUMO

Plastic film mulching has been extensively used for spring maize (Zea mays L.) production in the Hetao Irrigation District (HID). Determining whether transparent plastic film mulching results in premature senescence and yield reduction of spring maize still needs to be verified. A two-year field experiment was conducted in the HID that involved planting spring maize under three mulching practices on a flat plot 1) without mulching (control treatment, CK), 2) with black plastic film mulching (BM), 3) with transparent plastic film mulching (TM). The results indicated that TM and BM were superior to CK in terms of effects on soil hydrothermal conditions. Compared with BM, TM produced significantly higher soil temperature at V6, and had no significant temperature effect at V12, R1, R3, and R6. Both TM and BM promoted early seedling emergence and earlier silking, and TM extended the duration of the reproductive stages by 1-2 days compared with BM, and 4-5 days longer than CK. TM and BM produced greater kernel weights and kernel volumes in the superior and middle portions of the ear than CK. TM produced significantly greater total kernel weights per ear than BM at and after 23 days after silking. TM significantly increased grain-filling rate and length of the active grain-filling period compared with BM and CK. Additionally, TM and BM produced significantly higher photosynthetic parameters than CK at the grain-filling stage in the two study years. The net photosynthesis rate for TM was significantly greater than for BM. TM and BM significantly increased grain yields by 28.1% and 15.1%, respectively, in 2019 over CK, and by 24.6% and 21.1% in 2020. Transparent plastic film mulching could serve as a promising adaptive management practice to increase resource use efficiency and to improve maize productivity in the HID.

12.
Pathol Oncol Res ; 27: 598887, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34257554

RESUMO

Invasive nonfunctioning pituitary adenomas (NFPAs) grow rapidly and the mechanisms are unclear. Among many complex mechanisms, the role of immunity in the development of NFPAs has not been fully explored. Here, we analyzed the clinical features 146 NFPA patients who underwent trans-sphenoidal surgery or craniotomy and examined the effects of immune tolerance in invasiveness of NFPA patients using fluorescence-activated cell sorting and immunohistochemical methods. We found patients with invasive NFPAs had more visual deficits and defective fields, higher tumor size, and lower white blood cell count compared with patients with noninvasive NFPAs. Additionally, compared with patients with noninvasive NFPAs, patients with invasive NFPAs had conspicuously lower CD3-CD56+ natural killer (NK) cells and significantly higher levels of CD3+CD8+CD28-T cells (CD8+ Tregs) and interleukin-10 (IL-10) in peripheral blood. Moreover, patients with invasive NFPAs had lower infiltrated CD56+ cells, less infiltrated CD28+ cells, and significantly greater IL-10 expression. These results demonstrated that low CD56+ cells infiltration and CD28+ cells infiltration, as well as high IL-10 expression in pituitary tumor tissues, were related with increased invasiveness of NFPAs. Levels of CD3-CD56+ NK cells, CD8+ Tregs and IL-10 in the peripheral blood could be feasible diagnostic markers for invasive NFPAs.

13.
PLoS One ; 16(7): e0253988, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34260593

RESUMO

Due to difficulty in early diagnosis of Alzheimer's disease (AD) related to cost and differentiated capability, it is necessary to identify low-cost, accessible, and reliable tools for identifying AD risk in the preclinical stage. We hypothesized that cognitive ability, as expressed in the vocal features in daily conversation, is associated with AD progression. Thus, we have developed a novel machine learning prediction model to identify AD risk by using the rich voice data collected from daily conversations, and evaluated its predictive performance in comparison with a classification method based on the Japanese version of the Telephone Interview for Cognitive Status (TICS-J). We used 1,465 audio data files from 99 Healthy controls (HC) and 151 audio data files recorded from 24 AD patients derived from a dementia prevention program conducted by Hachioji City, Tokyo, between March and May 2020. After extracting vocal features from each audio file, we developed machine-learning models based on extreme gradient boosting (XGBoost), random forest (RF), and logistic regression (LR), using each audio file as one observation. We evaluated the predictive performance of the developed models by describing the receiver operating characteristic (ROC) curve, calculating the areas under the curve (AUCs), sensitivity, and specificity. Further, we conducted classifications by considering each participant as one observation, computing the average of their audio files' predictive value, and making comparisons with the predictive performance of the TICS-J based questionnaire. Of 1,616 audio files in total, 1,308 (81.0%) were randomly allocated to the training data and 308 (19.1%) to the validation data. For audio file-based prediction, the AUCs for XGboost, RF, and LR were 0.863 (95% confidence interval [CI]: 0.794-0.931), 0.882 (95% CI: 0.840-0.924), and 0.893 (95%CI: 0.832-0.954), respectively. For participant-based prediction, the AUC for XGboost, RF, LR, and TICS-J were 1.000 (95%CI: 1.000-1.000), 1.000 (95%CI: 1.000-1.000), 0.972 (95%CI: 0.918-1.000) and 0.917 (95%CI: 0.918-1.000), respectively. There was difference in predictive accuracy of XGBoost and TICS-J with almost approached significance (p = 0.065). Our novel prediction model using the vocal features of daily conversations demonstrated the potential to be useful for the AD risk assessment.

14.
Org Lett ; 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34261319

RESUMO

A copper-catalyzed four-component chloro-arylsulfonylation of styrene derivatives with aryldiazonium tetrafluoroborates, lithium chloride, and ex-situ generated sulfur dioxide (from SOgen) is presented. This sulfonylation features good functional group compatibility, mild reaction conditions, excellent regioselectivity, and good yields. The robustness and potential of this method have also been successfully demonstrated by a gram-scale reaction. Based on experimental study, a radical-involved mechanism is proposed for the transformation.

15.
PLoS One ; 16(7): e0254081, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34197541

RESUMO

Enterococci have the dual characteristics of being opportunistic pathogens and promising probiotics. The isolation from patients of CDC PNS-E2, a newly described Enterococcus species Enterococcus sanguinicola, may pose potential hazards. Enterococcus thailandicus from fermented sausage is a senior subjective synonym of E. sanguinicola. In this study, Enterococcus thailandicus TC1 was first isolated in healthy pigs in Tongcheng, China and identified by phenotypic analysis and 16S rRNA-based techniques. To evaluate the strain safety, an approach including virulence factors, antibiotic resistance, and animal experiments was adopted. The results show that cylA, gelE, esp, agg, ace, efaAfm, efaAfs, ptsD genes were undetected, and that the strain was sensitive or poorly resistant to some clinically relevant antibiotics. However, the isolated strain demonstrated ß-hemolytic activity in rabbit blood agar plates. Analysis of animal experiments revealed that the isolated strain had no adverse effect on translocation and the internal organ indices, though significant differences in histology (villi height, crypts height) of ileum were observed. The data acquired suggest that E. thailandicus TC1 may be associated with a potential health risk.

16.
BMC Public Health ; 21(1): 1298, 2021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34215244

RESUMO

BACKGROUND: The provision of public adaptive coping strategies to reduce psychological tension during the ongoing COVID-19 pandemic is critical. We sought to provide evidence-based guidance for psychological intervention, exploring the potential mediating roles of three sources of social support (i.e., subjective support, family support and counselor support) between coping strategies (i.e., cognitive coping, emotional coping and behavioral coping), and anxiety among college students at the height of the pandemic in China. METHODS: Using the Coping Strategy Questionnaire, Social Support Questionnaire, and Self-Rating Anxiety Scale, this large-scale online study analyzed the levels of social support, coping, and anxiety among 2640 college students in China from February 21st to 24th, 2020, when the students had been isolated at home for 1 month since the lockdown of Wuhan city. RESULTS: Students reported high levels of cognitive coping, behavioral coping, and social support. They also experienced low levels of anxiety and emotional coping. Anxiety was significantly and negatively related to coping and social support. The mediating roles of three sources of social support were found between cognitive coping, behavioral coping, and anxiety, respectively. However, the effect of emotional coping on anxiety was not found to be mediated by social support. CONCLUSIONS: Adopting positive coping strategies may enhance social support that in turn relieves anxiety. The effect of social support, especially family and counselor support, should arouse greater awareness in coping with the pandemic cognitively and behaviorally.


Assuntos
COVID-19 , Pandemias , Adaptação Psicológica , Ansiedade/epidemiologia , China/epidemiologia , Controle de Doenças Transmissíveis , Estudos Transversais , Humanos , SARS-CoV-2 , Apoio Social , Estudantes
19.
Artigo em Inglês | MEDLINE | ID: mdl-34284892

RESUMO

OBJECTIVES: To examine how mental illness (MI) and Alzheimer's disease and related dementias (ADRD) were associated with whether skilled nursing facility (SNF) residents returned to and remained in the community and if receipt of home health services was associated with post-SNF home time. DESIGN: Retrospective cohort study based on secondary data analyses. SETTING: New York State Medicare beneficiaries who were admitted to an SNF in 2014. PARTICIPANTS: Total of 46,137 older adults admitted to SNFs and 25,357 discharged from SNFs to home. MEASUREMENTS: We used Medicare claims and assessment databases to derive our outcomes (discharge to the community and home time [i.e., days alive in the community]), determine MI/ADRD status, and obtain socio-demographic and clinical characteristics. RESULTS: Among SNF admissions, 22.9% had MI, 22.6% had ADRD, and 59.0% were discharged to the community. In analyses adjusting for socio-demographic and clinical characteristics, MI and ADRD were associated with decreased odds of community discharge and less home time during 90-days of follow-up. However, when we included depressive symptoms, aggressive behaviors, and daily functioning in the analyses, these associations were attenuated. Receipt of post-SNF home health services was associated with increased home time among those with MI or ADRD. CONCLUSION: Newly admitted SNF residents with MI or ADRD were less likely to be discharged and, if discharged, spent less time in the community. Interventions targeting depressive symptoms, aggressive behaviors, and functioning and improving linkage with home health services may help decrease differences in post-acute care trajectories between those with and without MI and ADRD.

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