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1.
Phytother Res ; 2021 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-33792976

RESUMO

Melanoma is the most common type of skin cancer. Signal transducer and activator of transcription 3 (STAT3) signaling has been demonstrated to be a therapeutic target for melanoma. Dauricine (Dau), an alkaloid compound isolated from the root of Menispermum dauricum DC., has shown tumor-suppressing effects in multiple human cancers, but its potential in melanoma remains unexplored. In this study, we demonstrated that Dau significantly inhibited the viability and proliferation of A375 and A2058 melanoma cells. Death of melanoma cells was also markedly promoted by Dau. Moreover, Dau inhibited phosphorylation-mediated activation of STAT3 and Src in a dose-dependent manner. Notably, constitutive activation of Src partially abolished the antiproliferative and cytotoxic activities of Dau on melanoma cells. Molecular docking showed that Dau could dock on the kinase domain of Src with a binding energy of -10.42 kcal/mol. Molecular dynamics simulations showed that Src-Dau binding was stable. Surface plasmon resonance imaging analysis also showed that Dau has a strong binding affinity to Src. In addition, Dau suppressed the growth of melanoma cells and downregulated the activation of Src/STAT3 in a xenograft model in vivo. These data demonstrated that Dau inhibits proliferation and promotes cell death in melanoma cells by inhibiting the Src/STAT3 pathways.

2.
Chin J Traumatol ; 2021 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-33903003

RESUMO

PURPOSE: Wallerian degeneration (WD) is an antegrade degenerative process distal to peripheral nerve injury. Numerous genes are differentially regulated in response to the process. However, the underlying mechanism is unclear, especially the early response. We aimed at investigating the effects of sciatic nerve injury on WD via CLDN 14/15 interactions in vivo and in vitro. METHODS: Using the methods of molecular biology and bioinformatics analysis, we investigated the molecular mechanism by which claudin 14/15 participate in WD. Our previous study showed that claudins 14 and 15 trigger the early signal flow and pathway in damaged sciatic nerves. Here, we report the effects of the interaction between claudin 14 and claudin 15 on nerve degeneration and regeneration during early WD. RESULTS: It was found that claudin 14/15 were upregulated in the sciatic nerve in WD. Claudin 14/15 promoted Schwann cell proliferation, migration and anti-apoptosis in vitro. PKCα, NT3, NF2, and bFGF were significantly upregulated in transfected Schwann cells. Moreover, the expression levels of the ß-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK signaling pathways were also significantly altered. CONCLUSION: Claudin 14/15 affect Schwann cell proliferation, migration, and anti-apoptosis via the ß-catenin, p-AKT/AKT, p-c-jun/c-jun, and p-ERK/ERK pathways in vitro and in vivo. The results of this study may help elucidate the molecular mechanisms of the tight junction signaling pathway underlying peripheral nerve degeneration.

3.
Org Lett ; 23(6): 2212-2216, 2021 Mar 19.
Artigo em Inglês | MEDLINE | ID: mdl-33683891

RESUMO

A cobalt-catalyzed dearomatization of indoles via transfer hydrogenation with HBpin and H2O has been developed. This reaction offered a straightforward platform to access hexahydropyrido[1,2-a]indoles in high regio- and chemoselectivity. A preliminary reaction mechanism was proposed on the basis of deuterium-labeling experiments, and a cobalt hydride species was involved in the reaction.

4.
J Nucl Cardiol ; 28(2): 464-477, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33751472

RESUMO

BACKGROUND: A low appropriate therapy rate indicates that a minority of patients will benefit from their implantable cardioverter defibrillator (ICD). Quantitative measurements from 18F-fluorodeoxyglucose positron emission tomography (18F-FDG PET) may predict ventricular arrhythmia (VA) occurrence after ICD placement. METHODS: We performed a prospective observational study and recruited patients who required ICD placement. Pre-procedure image scans were performed. Patients were followed up for VA occurrence. Associations between image results and VA were analyzed. RESULTS: In 51 patients (33 males, 53.9 ± 17.2 years) analyzed, 17 (33.3%) developed VA. Compared with patients without VA, patients with VA had significantly larger values in scar area (17.7 ± 12.4% vs. 7.0 ± 7.9%), phase standard deviation (51.4° ± 14.0° vs. 34.0° ± 15.0°), bandwidth (172.9° ± 39.8° vs. 128.7° ± 49.9°), sum thickening score (STS, 29.5 ± 11.1 vs. 17.8 ± 13.2), and sum motion score (42.9 ± 11.5 vs. 33.0 ± 19.0). Cox regression analysis and receiver operating characteristic curve analysis showed that scar size, dyssynchrony, and STS were associated with VA occurrence (HR, 4.956, 95% CI 1.70-14.46). CONCLUSION: Larger left ventricular scar burden, increased dyssynchrony, and higher STS quantified by 18F-FDG PET may indicate a higher VA incidence after ICD placement.

6.
J Neurosci ; 41(9): 1928-1940, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33441435

RESUMO

Choice behavior is characterized by temporal discounting, i.e., preference for immediate rewards given a choice between immediate and delayed rewards. Agouti-related peptide (AgRP)-expressing neurons located in the arcuate nucleus of the hypothalamus (ARC) regulate food intake and energy homeostasis, yet whether AgRP neurons influence choice behavior and temporal discounting is unknown. Here, we demonstrate that motivational state potently modulates temporal discounting. Hungry mice (both male and female) strongly preferred immediate food rewards, yet sated mice were largely indifferent to reward delay. More importantly, selective optogenetic activation of AgRP-expressing neurons or their axon terminals within the posterior bed nucleus of stria terminalis (BNST) produced temporal discounting in sated mice. Furthermore, activation of neuropeptide Y (NPY) type 1 receptors (Y1Rs) within the BNST is sufficient to produce temporal discounting. These results demonstrate a profound influence of hypothalamic signaling on temporal discounting for food rewards and reveal a novel circuit that determine choice behavior.SIGNIFICANCE STATEMENT Temporal discounting is a universal phenomenon found in many species, yet the underlying neurocircuit mechanisms are still poorly understood. Our results revealed a novel neural pathway from agouti-related peptide (AgRP) neurons in the hypothalamus to the bed nucleus of stria terminalis (BNST) that regulates temporal discounting in decision-making.

7.
J Ethnopharmacol ; 270: 113838, 2021 Apr 24.
Artigo em Inglês | MEDLINE | ID: mdl-33460756

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Myocardial fibrosis after myocardial infarction (MI) leads to cardiac remodeling and loss of function. Taohong siwu decoction (THSWD), a well-known traditional Chinese medicinal prescription, has been clinically used to treat various cardiovascular and cerebrovascular diseases, but its potential functions in myocardial fibrosis after MI remain uncharacterized. AIM OF THE STUDY: The purpose of current study was to explore the potential mechanism action and anti-myocardial fibrosis effects of treatment with THSWD in vivo and in vitro. MATERIALS AND METHODS: Mouse underwent ligation of coronary artery to induce MI and divided equally into the sham group, model group and THSWD treatment groups. After 4 weeks, the effects of THSWD treatment on cardiac function were estimated by echocardiography. HE staining was used to detect the pathologic changes and Masson trichrome staining was used to estimate tissue fibrosis. To further explore the regulatory molecular mechanisms of THSWD, transcriptome analysis was performed. Furthermore, in vitro, we investigated the effect of THSWD on cell proliferation and collagen deposition in primary cardiac fibrosis cells and its possible mechanism of action. Overexpression of TGFBR1 was achieved by infection with an adenovirus vector encoding TGFBR1. RESULTS: Treatment with THSWD significantly decreased myocardial fibrosis and recovered cardiac function in the post-MI mouse. The transcriptomics data imply that the TGF-ß pathway might be a target in the anti-fibrosis effect of THSWD. THSWD inhibits TGF-ß1-induced proliferation of primary cardiac fibroblasts. THSWD decreased collagen expression and TGFBR1 and Smad2/3 phosphorylation. Moreover, the inhibitory effect of THSWD on CFs proliferation and collagen deposition, as well as TGFBR1 signaling pathway-associated proteins expression was partially abrogated by overexpression of TGFBR1. CONCLUSION: Collectively, the results implicate that THSWD attenuates myocardial fibrosis by inhibiting fibrosis proliferation and collagen deposition via inhibiting TGFBR1, and might be a potential therapeutic agent for treatment of myocardial fibrosis post-MI.

8.
J Biochem Mol Toxicol ; : e22732, 2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33512044

RESUMO

Zinc finger protein 667-antisense RNA 1 (ZNF667-AS1) is a member of the C2 H2 zinc finger protein family. However, the exact effect of ZNF667-AS1 in uveal melanoma (UM) progression has not been elucidated. The biological roles of ZNF667-AS1 and MEGF10 were assessed using cell counting kit-8 and flow cytometry. Quantitative reverse-transcription polymerase chain reaction and Western blot analyses were conducted to measure the expression of subjects. ZNF667-AS1 expression was significantly decreased in metastasized UM tissues and its low expression was related to poorer prognosis of UM patients. MEGF10 expression was positively associated with ZNF667-AS1 expression. The inhibitory effect of ZNF667-AS1 overexpression on UM cellular malignant behaviors could be reversed by MEGF10 knockdown, which was re-ascertained by the detection of corresponding protein levels (p53, cyclin D1, Bcl-2, and Bax). In conclusion, ZNF667-AS1 might play an inhibitory role in the development of UM by regulating cellular aggressiveness, which was partially realized by positively regulating MEGF10.

9.
Aging (Albany NY) ; 122020 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-33263567

RESUMO

The current study was designed to seek the role of the glycogen synthase kinase-3ß (GSK-ß)-regulated NF-E2-related factor 2 (Nrf2) pathway in the antioxidant effect induced by Apigenin-7-O-ß-D-(-6"-p-coumaroyl)-glucopyranoside (APG). Rat primary cultured cortical neurons were challenged by oxygen and glucose deprivation/reoxygenation (OGD/R) and then treated with APG. Cell viability, phosphorylation of GSK-ß at Ser9 and nuclear expression of Nrf2 were measured. Male Sprague Dawley rats challenged by 2-h middle cerebral artery occlusion were treated with 50 mg/kg APG, and the neurological score, infarct volume, phosphorylation of GSK-3ß and nuclear expression of Nrf2 were analyzed. The neuroprotective effect of APG and the expression levels of antioxidant enzymes and oxidative products were also examined in the presence and absence of Nrf2-siRNA and PI3K inhibitors. APG reduced the apoptotic proportion, attenuated LDH release and increased cell viability, and in vivo, APG improved neurological scores and reduced infarct volume. APG increased GSK-3ß phosphorylation and Nrf2 nuclear translocation, while these effects were prevented by PI3K inhibitors or Nrf2-siRNA treatment in both OGD/R cell cultures and ischemic/reperfusion rats. These findings reveal that GSK-3ß phosphorylation-mediated Nrf2 activation is involved in the neuroprotective effect of APG.

10.
Epilepsy Behav ; : 107572, 2020 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-33268015

RESUMO

OBJECTIVE: The goal of this study was to evaluate the predictive capacity of four scoring tools: the Status Epilepticus Severity Score (STESS), the Encephalitis-NCSE-Diazepam resistance-Image abnormalities-Tracheal intubation (END-IT) score, and two variable combinations of the Epidemiology-based Mortality Score in Status Epilepticus (EMSE) in younger and older adult patients with status epilepticus (SE). METHODS: We present a retrospective hospital-based analysis with a focus on adult patients with SE at three tertiary care hospitals in the Zhejiang province of China. Data were collected from January 2013 to December 2018. The patients were divided into two groups: younger adult patients (18-64 years old) and older adult patients (≥65 years old). Clinical outcomes (dead or alive) were assessed at hospital discharge. The four scoring tools were used to predict in-hospital mortality in both younger and older adult patients. RESULTS: The mortality rate in older adult patients (25.4%) was higher than in younger adult patients (12.9%). Compared with the elderly, the younger adult patients had a higher proportion of encephalitis, while acute cerebrovascular disease and Charlson Complications Index (CCI) were lower. For the younger adult patients, END-IT had the largest area under the curve (AUC) of 0.843 (95% CI, 0.772-0.899), which was higher than the EMSE-EAL value of 0.687 (95% CI, 0.603-0.763, p < 0.05) and EMSE-EAC of 0.646 (95% CI, 0.561-0.725, p < 0.05). For the older adult patients, EMSE-EAL had the largest AUC of 0.843 (95% CI, 0.738-0.919), which was significantly higher than STESS with an AUC of 0.676 (95% CI, 0.554-0.782, p < 0.05). Moreover, the AUC of EMSE-EAL in the elderly was larger than in younger adult patients. The cutoffs in younger adult patients were STESS ≥ 4 (sensitivity 0.444, specificity 0.951), END-IT ≥ 3 (sensitivity 0.833, specificity 0.672), EMSE-EAL ≥ 31 (sensitivity 0.778, specificity 0.566), and EMSE-EAC ≥ 33 (sensitivity 0.833, specificity 0.492). However, the cutoffs in older adult patients were STESS ≥ 5 (sensitivity 0.500, specificity 0.925), END-IT ≥ 2 (sensitivity 0.944, specificity 0.547), EMSE-EAL ≥ 30 (sensitivity 0.944, specificity 0.623), and EMSE-EAC ≥ 31 (sensitivity 0.944, specificity 0.415). CONCLUSION: Our results indicated that the STESS, END-IT, EMSE-EAC, and EMSE-EAL scores have excellent capacity to predict in-hospital mortality in both younger and older adult patients with SE. Our study supports the use of END-IT in patients under 65 years of age and suggests that EMSE-EAL is the most suitable scoring tool for patients over 65.

11.
Food Res Int ; 137: 109409, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33233096

RESUMO

This study investigated the effects of L-theanine supplementation on the colonic mucosa injury in C57BL/6J male mice treated with dextran sulfate sodium (DSS)-induced colitis. Treatment with L-theanine significantly decreased the disease activity index and ameliorated the inflammation-associated pathological damage in colon length, as well as the histopathological features of DSS-induced colitis. L-Theanine administration also inhibited DSS-induced changes in the colonic tissue that included myeloperoxidase by 4.5-fold and malondialdehyde by 2.3-fold in comparison to the DSS group. In addition, GSH was increased by 85% and lipopolysaccharides level was decreased by 55% in comparison to the DSS group. Proinflammatory cytokines expression, including interleukin (IL)-1ß, IL-6, and tumor necrosis factor-α, at the both protein and mRNA levels were also decreased significantly. Notably, the increase in serum content of lipopolysaccharides and colonic expressions of inducible nitric oxide synthase, cyclooxygenase-2, toll like receptor (TLR)-2, TLR-4, TLR-6, and TLR-9 induced by DSS were also significantly inhibited by L-theanine administration. In addition, L-theanine also attenuated the reduction of serum contents of diamine oxidase and the production of short-chain fatty acids in the colonic tissue, and gene expression of mucosal barrier zonula occludens-1 and claudin-1 in DSS-induced colitis. Furthermore, 16S rRNA phylogenetic sequencing revealed a shift in microbial community composition induced by DSS, but no significant difference was observed following L-theanine supplementation. Overall, our findings demonstrated that L-theanine inhibits intestinal inflammation and protects against intestinal barrier disruption in mice with DSS-induced colitis. Further clinical trials should be considered to assess the effects of L-theanine supplementation on oxidative and inflammatory responses in humans.

12.
J Adolesc Health ; 67(5S): S14-S23, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33246529

RESUMO

PURPOSE: The purpose of the study was to propose a health indicator system responsive to current Chinese adolescent health needs and identify data gaps in current information systems. METHODS: We identified 186 keywords for adolescent health gathered from three sources: contributors to the burden of disease captured in the Global Burden of Diseases 2015, together with independent literature and expert desk reviews; major health-related policies released by the State Council of China; and global strategies issued by UN agencies over the past five years. All keywords were synthesized into indicators and ranked with core indicators identified through panel discussions and literature review. A further systematic review was conducted to identify data sources for each indicator. RESULTS: We identified 100 indicators which we categorized into five dimensions: health outcomes including adolescent mortality and morbidity; health knowledge, skills and risk behaviors including smoking, physical activity; demographic and socioeconomic status including education or employment; responsiveness of the health service system including the provision of health education at school; and the physical and social environments including safe drinking water, secondhand smoke exposure, injuries, and bullying. In total, 72 indicators had nationally representative data, including 22 out of 24 core indicators (91.7%), 27 out of 33 potential core indicators (81.8%), and 23 out of 43 general indicators (53.5%). A large proportion of these indicators rely solely on data from school or household surveys. CONCLUSIONS: The proposed health indicator system has the potential to rapidly identify shifting priorities for adolescent health in China but will require greater investment in primary data collection in neglected areas.

13.
PLoS One ; 15(10): e0239736, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33002008

RESUMO

The identification of anammox bacteria is mostly relied on PCR with various marker genes. However, the community composition revealed by different marker genes and whether the marker genes influence the resulted community composition remain unclear. We compared the community structure of anammox bacteria in enriched and natural environments revealed by 16S rRNA and functional genes (hzo, hzsA and hzsB) from public database and published papers. The genus of Ca. Scalindua showed the lowest similarities with other genera, especially for the hzsA gene (66.9%-68.6%). The 16S rRNA gene is the most commonly used marker gene in natural habitats with 151 out 221 papers in total. The anammox bacterial community composition is distributed according to the source of habitat regardless the use of various marker genes. The role of marker gene is limited with explanatory of 5.4% for variance of community composition, versus 20.5% of habitat. The effect of marker gene is mainly acted on freshwater habitat, which shows significant different community composition revealed by 16S rRNA and hzo, with Ca. Brocadia and Ca. Jettenia as dominant genus, respectively.


Assuntos
Amônia/metabolismo , Bactérias Anaeróbias/genética , Genes Bacterianos/genética , Viés , Ecossistema , Marcadores Genéticos/genética , Reação em Cadeia da Polimerase/métodos , RNA Ribossômico 16S/genética
14.
Sci Rep ; 10(1): 17810, 2020 10 20.
Artigo em Inglês | MEDLINE | ID: mdl-33082378

RESUMO

Sphagneticola trilobata (L.) Pruski is one of the fast-growing malignant weeds in South China. It has severely influenced local biodiversity and native plant habitat. Photosynthesis is the material basis of plant growth and development. However, there are few reports on the photosynthetic transcriptome of S. trilobata. In this study, S. trilobata had a relatively large leaf area and biomass. The gas exchange parameters per unit area of leaves, including net photosynthetic capacity (Pn), intercellular CO2 (Ci), stomatal conductance (Gs), transpiration rate (Tr), water use efficiency (WUE), photosynthetic pigment and Rubisco protein content were higher than those of the native plant Sphagneticola calendulacea (L.) Pruski. On this basis, the differences in photosynthesis pathways between the two Sphagneticola species were analyzed by using the Illumina HiSeq platform. The sequencing results for S. trilobata and S. calendulacea revealed 159,366 and 177,069 unigenes, respectively. Functional annotation revealed 119,350 and 150,846 non-redundant protein database annotations (Nr), 96,637 and 115,711 Swiss-Prot annotations, 49,159 and 60,116 Kyoto Encyclopedia of Genes and Genomes annotations (KEGG), and 83,712 and 97,957 Gene Ontology annotations (GO) in S. trilobata and S. calendulacea, respectively. Additionally, our analysis showed that the expression of key protease genes involved in the photosynthesis pathway, particularly CP43, CP47, PsbA and PetC, had high expression levels in leaves of S. trilobata in comparison to native species. Physiological and transcriptomic analyses suggest the high expression of photosynthetic genes ensures the high photosynthetic capacity of leaves, which is one of the inherent advantages underlying the successful invasion by S. trilobata.

16.
Life Sci ; 260: 118417, 2020 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-32931801

RESUMO

AIMS: Colorectal cancer (CRC) is one of the most common cancers. However, the effective and non-invasive diagnostic biomarkers for the detection of CRC metastasis remain unsatisfied. Here, we aimed to evaluate the diagnostic performance of stool miR-135b-5p (a potential biomarker) for metastasis of CRC patients. MATERIALS AND METHODS: Serum and stool specimens from 77 patients with CRC and 29 normal controls were collected for miRNA purification. Real-time quantitative PCR was used for the relative quantification of miR-135b-5p expression. Receiver operating and characteristic (ROC) curve analysis was used to estimate the diagnostic performance of stool/serum miR-135b-5p for CRC metastasis. Dual-luciferase reporter assay was conducted to determine miR-135b-5p's target gene. Besides, a trans-well matrigel assay was performed to evaluate the invasion ability of HT-29 cell lines. KEY FINDINGS: Stool miR-135b-5p expression was dramatically up-regulated in CRC patients, and it effectively distinguished the CRC patients from normal controls with 74.1% of specificity and 96.5% of sensitivity. Moreover, stool miR-135b-5p exhibited a better diagnostic performance in distinguishing the different TNM stages of CRC patients than serum miR-135b-5p. In the molecular mechanism, our observations indicated that miR-135-5p directly targets the mRNA of ZNRF3, and then activates the Wnt pathway. Over-expression of ZNRF3 in HT-29 cells obviously reversed miR-135b-5p's effects on cell invasion and migration, indicating miR-135b-5p achieves its biological functions in a ZNRF3 dependent manner. SIGNIFICANCE: MiR-135b-5p may be a promising non-invasive biomarker for the diagnosis of CRC patients with TNM stage-III/IV and a potential candidate to develop an intervention strategy for colorectal cancer.


Assuntos
Biomarcadores Tumorais/genética , Movimento Celular , Neoplasias Colorretais/diagnóstico , Fezes/química , Regulação Neoplásica da Expressão Gênica , MicroRNAs/genética , Apoptose , Estudos de Casos e Controles , Proliferação de Células , Neoplasias Colorretais/sangue , Neoplasias Colorretais/genética , Humanos , Estadiamento de Neoplasias , Curva ROC , Células Tumorais Cultivadas
17.
Photosynth Res ; 2020 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-32902777

RESUMO

Increasing amounts of experimental evidence show that anthocyanins provide physiological protection to plants under stress. However, the difference in photoprotection mediated by anthocyanins and other photoprotective substances in different seasons is still uncertain. To determine the relationship between anthocyanin accumulation and the photoprotective effects in different seasons, Castanopsis chinensis and Acmena acuminatissima, whose anthocyanin accumulation patterns differ in different seasons, were used as materials to explain how plants adapt to different seasons; as such, their physiological and biochemical responses were analyzed. Young leaves of C. chinensis and A. acuminatissima presented different colors in the different seasons. In summer, the young leaves of C. chinensis were purplish red, while those of A. acuminatissima were light green. In winter, the young leaves of C. chinensis were light green, while those of A. acuminatissima were red. Compared with the young red leaves, the young light green leaves that did not accumulate anthocyanins had higher flavonoid and phenolics contents, total antioxidant capacity, non-photochemical quenching (NPQ), and relative membrane leakage, and a slower recovery rate in the maximum photochemical efficiency (Fv/Fm) after high-light treatment. In addition, the net photosynthesis rate (Pn), transpiration rate (Tr), stomatal conductance (gs), and the effective quantum yield of PSII (ΦPSII) of the young leaves in winter were significantly lower than those in summer, while the activities of catalase (CAT, EC 1.11.1.6), peroxidase (POD, EC 1.11.1.7), and superoxide dismutase (SOD, EC 1.15.1.1) were significantly higher than those in summer. These data indicate that to adapt to seasonal changes anthocyanins, other antioxidative substances and antioxidative enzymes, as well as components involved in the safe dissipation of excitation energy as heat need to cooperate with one another.

18.
Rejuvenation Res ; 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32746712

RESUMO

Electroacupuncture (EA) pretreatment induces cerebral ischemic tolerance; however, the mechanism remains poorly understood. This study aimed to determine the participation of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α)-mediated mitochondrial biogenesis in the neuroprotection of EA and whether cannabinoid receptor 1 (CB1R) is involved in this mechanism. At 2 hours after EA pretreatment, adult male C57BL/6j mice were subjected to 60-minute right middle cerebral artery occlusion (MCAO). Mitochondrial function, the level of mitochondrial biogenesis-related proteins (nuclear transcription factor 1, NRF1; mitochondrial transcription factor A, TFAM), and mitochondrial DNA (mtDNA) were measured. A small interfering RNA (siRNA) targeting PGC-1α and the CB1R antagonists AM251 and SR141716A were given to the animals before EA pretreatment, and mitochondrial function and biogenesis were examined after MCAO. EA ameliorated the mitochondrial function, upregulated the NRF1 and TFAM expression, and increased the mtDNA levels and the volume and number of mitochondria. EA pretreatment increased the expression of PGC-1α, whereas the PGC-1α siRNA and CB1R antagonists reversed the improved neuroprotection and increased mitochondrial biogenesis induced by EA. Our results indicated that EA pretreatment protects the mitochondria and promotes mitochondrial biogenesis by activating CB1R-dependent PGC-1α, which provides a novel mechanism for EA pretreatment-induced ischemic tolerance.

19.
J Shanghai Jiaotong Univ Sci ; 25(4): 409-416, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32834699

RESUMO

It is critical for the recovery of manufacturing industry against COVID-19 by analyzing its impact from supply chain perspective and exploring corresponding countermeasures. Firstly, this paper studies the initial impact caused by worldwide spread of the coronavirus, such as production disruption of raw material and spare parts, unsatisfied market demand due to setbacks in logistics, increasing bankruptcy risk for small and mediumsized enterprises (SMEs), and demand fluctuation enlargement. Secondly, the aftershock of COVID-19 is analyzed. With the trend of regionalization and digitalization, two-step countermeasures are proposed to help the recovery of manufacturing industry within the pandemic and better prepare for the post-COVID-19 world from supply chain perspective.

20.
BMC Musculoskelet Disord ; 21(1): 449, 2020 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-32646398

RESUMO

BACKGROUND: Clinically, skeletal muscle ischemia/reperfusion injury is a life-threatening syndrome that is often caused by skeletal muscle damage and is characterized by oxidative stress and inflammatory responses. Bilobalide has been found to have antioxidative and anti-inflammatory effects. However, it is unclear whether bilobalide can protect skeletal muscle from ischemia/reperfusion injury. METHODS: The effects of bilobalide on ischemia/reperfusion-injured skeletal muscle were investigated by performing hematoxylin and eosin staining and assessing the wet weight/dry weight ratio of muscle tissue. Then, we measured lipid peroxidation, antioxidant activity and inflammatory cytokine levels. Moreover, Western blotting was conducted to examine the protein levels of MAPK/NF-휅B pathway members. RESULTS: Bilobalide treatment could protected hind limb skeletal muscle from ischemia/reperfusion injury by alleviating oxidative stress and inflammatory responses via the MAPK/NF-휅B pathways. CONCLUSIONS: Bilobalide may be a promising drug for I/R-injured muscle tissue. However, the specific mechanisms for the protective effects still need further study.

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