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1.
J Pharm Pharmacol ; 73(2): 272-280, 2021 Mar 04.
Artigo em Inglês | MEDLINE | ID: mdl-33793797

RESUMO

OBJECTIVES: Stroke is one of the leading causes of disability and death worldwide, and ischaemic stroke is the most common subtype. Moreover, we found that L-borneol has an obvious therapeutic effect on cerebral ischaemia. This study aimed to investigate the potential mechanism of L-borneol in permanent middle cerebral artery occlusion (pMCAO) rats via the mitochondrial calcium uniporter (MCU)-related apoptosis cascade. METHODS: A pMCAO model was used to simulate cerebral ischaemia, and neurological function was evaluated. Cerebral infarction was observed by TTC staining. HE staining was also used to reflect the pathophysiological changes in the rat hippocampus and cortex. Furthermore, MCU-related signals and apoptosis signalling pathways were detected at both the gene and protein levels. RESULTS: The neurological function scores of the high-dose L-borneol (H-B) group, medium-dose L-borneol (M-B) group and low-dose L-borneol (L-B) group were significantly lower than that of the model group at 24 h (P < 0.05, P < 0.01). High and medium doses of L-borneol could reverse the cerebral infarction area, similar to Nimotop. After HE staining, the cells in the H-B group and M-B group were neatly and densely arranged, with largely normal morphological structures. High-dose L-borneol could significantly reduce the gene and protein levels of Apaf-1, Bad and Caspase-3 and increase the expression of Bcl-2 (P < 0.05, P < 0.01). In addition, the MCU expression of the H-B group was significantly decreased compared with that of the model group at both the gene and protein levels (P < 0.05, P < 0.01). The expression of IDH2 was similar to that of MCU but not MEP (P < 0.05, P < 0.01). CONCLUSION: L-borneol can achieve brain protection by downregulating the excessive expression of MCU-related signalling pathway and further inhibiting the apoptosis of neurons during pMCAO.

2.
Protein Sci ; 2021 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-33813796

RESUMO

The COVID-19 epidemic is one of the most influential epidemics in history. Understanding the impact of coronaviruses (CoVs) on host cells is very important for disease treatment. The SARS-CoV-2 envelope (E) protein is a small structural protein involved in many aspects of the viral life cycle. The E protein promotes the packaging and reproduction of the virus, and deletion of this protein weakens or even abolishes the virulence. This review aims to establish new knowledge by combining recent advances in the study of the SARS-CoV-2 E protein and by comparing it with the SARS-CoV E protein. The E protein amino acid sequence, structure, self-assembly characteristics, viroporin mechanisms and inhibitors are summarized and analyzed herein. Although the mechanisms of the SARS-CoV-2 and SARS-CoV E proteins are similar in many respects, specific studies on the SARS-CoV-2 E protein, for both monomers and oligomers, are still lacking. A comprehensive understanding of this protein should prompt further studies on the design and characterization of effective targeted therapeutic measures.

3.
BMJ Case Rep ; 14(4)2021 Apr 02.
Artigo em Inglês | MEDLINE | ID: mdl-33811091

RESUMO

We report a case of a 55-year-old man presenting with diplopia, masticatory weakness and dysarthria several weeks post multitrauma. The clinical suspicion of myasthenia gravis (MG) was supported with positive acetylcholine receptor antibodies and abnormal repetitive stimulation study. He responded well to pyridostigmine, intravenous immunoglobulin and oral prednisolone. In this report, we describe the timing and progression of MG in our patient, and review the literature pertaining to the relationship between trauma and MG. The search for definitive evidence of causation may be impractical, but should not delay the recognition and management of a treatable condition.

4.
Food Chem ; 356: 129678, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33812185

RESUMO

This study investigated the effect of frozen storage periods (0, 2, 4, 6, or 8 weeks) of raw meat and stewing on the flavor of chicken broth. With the increased storage duration of frozen raw material, the contents of the free amino acids, nucleotides and mineral elements in the broth decreased significantly, especially within the first 4 weeks, and then increased significantly. Meanwhile, the volatile compounds showed the reverse trend. The results from the E-nose, E-tongue and sensory evaluation indicated a progressive difference in overall flavor profiles between the samples. The sensory scores of the meaty and fatty traits reached a maximum as raw chicken meat was stored for 4 weeks at -18 °C, which should be related to the increased contents of aldehydes and 2-pentyl furan. Overall, the limited storage duration of frozen raw meat can enhance the flavor of chicken broth.

5.
J Ethnopharmacol ; 275: 114045, 2021 Apr 05.
Artigo em Inglês | MEDLINE | ID: mdl-33831463

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Dang-Gui-Si-Ni (DGSN) decoction as a classic prescription has been widely used for thousands of years in the clinical practice of traditional Chinese medicine (TCM). Especially in recent years, the potential efficacy of TCM for the treatment of Raynaud's syndrome has attracted great attention as there are still no specific remedies for this disease. However, the active constituents and underlying mechanisms responsible for the therapeutic benefits are not well understood, which makes it difficult to ensure quality control or to design research and drug development strategies. To identify the potential pharmacodynamic ingredients (PPIs) of TCM will help to achieve suitable process control procedures for industrial production and large-scale manufacturing. AIM OF THE STUDY: In the present study, we propose a multi-dimensional qualitative analysis method combining water-decoction spectra, in-vitro intestinal absorption spectra, in-vivo plasma spectra, and molecular docking of components to quickly identify the PPIs for the DGSN decoction of TCM. MATERIALS AND METHODS: Water-based decoctions of DGSN were prepared in accordance with the clinical use registered in ancient books. Ultra-high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS) coupled with computerized modelling activity screening was used to quickly identify the PPIs of the DGSN decoction. Bioactive compounds absorbed in vitro were identified using the everted intestinal sac model from rats and compounds absorbed in vivo were confirmed in portal vein blood samples obtained following oral administration in rats. Molecular docking validation experiments were adopted to predict the binding activity to coagulation factors I, II, VII, X, and IX. The active components were further confirmed by pharmacodynamics analysis. The anticoagulant activity of the DGSN decoction was verified using rat models. RESULTS: Thirty-one compounds were identified in the DGSN decoction. According to the in vivo experiments, 22 compounds that could be absorbed in vivo were detected by the everted intestinal sac model in rats. This model greatly reduces the scope of PPIs and is easy to perform. Ten compounds were detected in the portal vein blood in rats. The compounds detected in plasma provide stronger evidence supporting the PPIs. Molecular docking in vitro experiments indicated that 7 compounds exhibited better binding activity with coagulation factors I, II, VII, X, and IX. The animal experiments confirmed that the DGSN decoction could improve the microcirculation, providing indirect proof of anticoagulant activity suggested by the molecular docking studies. Finally, based on the multi-dimensional methods, 9 potential compounds present in the DGSN decoction were identified as PPIs (i.e., ferulic acid, paeoniflorin, albiflorin, chlorogenic acid, cryptochlorogenic acid, liquiritin, liquiritin apioside, cinnamaldehyde and glycyrrhizic acid). CONCLUSION: Overall, this study combined the water-decoction spectra, intestinal absorption spectra in vitro, plasma spectra in vivo, and molecular docking studies to establish a multi-dimensional qualitative analysis method of the DGSN decoction. Meanwhile, 9 compounds in DGSN decoction were identified as PPIs using this method, and are proposed for application as quality standards for complex TCM prescriptions.

6.
Food Chem ; 354: 129510, 2021 Mar 09.
Artigo em Inglês | MEDLINE | ID: mdl-33752113

RESUMO

This study aimed to investigate the combined effects of a coating based on shellac and the active agent tannic acid (TA) on the storability and physiological variations of mangoes stored at room temperature. Results showed that TA-shellac prolonged shelf life and improved overall quality of mangoes to a higher extent compared with controls, which was reflected in the extension of shelf life for approximately 10 days, maintaining of tissue firmness and weight loss, slowing down of respiration rate, improvement of physical properties and chemical qualities, suppression of browning, reduction of lipid peroxidation, preservation of aromatic volatiles, and regulation of the related enzymes activities. Addition of TA to shellac coating also improved the antifungal effect of the formulation. The results suggest that a synergistic effect took place between TA and shellac, which demonstrates the high potential for shelf life extension and quality improvement of mangoes of this formulation.

7.
PLoS One ; 16(3): e0248634, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33735310

RESUMO

Glioma is a lethal malignant brain cancer, and many reports have shown that abnormalities in the behavior of water and ion channels play an important role in regulating tumor proliferation, migration, apoptosis, and differentiation. Recently, new studies have suggested that some long noncoding RNAs containing small open reading frames can encode small peptides and form oligomers for water or ion regulation. However, because the peptides are difficult to identify, their functional mechanisms are far from being clearly understood. In this study, we used bioinformatics methods to identify and evaluate lncRNAs, which may encode small transmembrane peptides in gliomas. Combining ab initio homology modeling, molecular dynamics simulations, and free energy calculations, we constructed a predictive model and predicted the oligomer channel activity of peptides by identifying the lncRNA ORFs. We found that one key hub lncRNA, namely, DLEU1, which contains two smORFs (ORF1 and ORF8), encodes small peptides that form pentameric channels. The mechanics of water and ion (Na+ and Cl-) transport through this pentameric channel were simulated. The potential mean force of the H2O molecules along the two ORF-encoded peptide channels indicated that the energy barrier was different between ORF1 and ORF8. The ORF1-encoded peptide pentamer acted as a self-assembled water channel but not as an ion channel, and the ORF8 permeated neither ions nor water. This work provides new methods and theoretical support for further elucidation of the function of lncRNA-encoded small peptides and their role in cancer. Additionally, this study provides a theoretical basis for drug development.

8.
Chemosphere ; 271: 129740, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33736212

RESUMO

Di(2-ethylhexyl) phthalate (DEHP) has been well acknowledged for its endocrine disruption and associated metabolic diseases, leading to the search for safer industrial alternatives including di-isononyl phthalate (DINP). However, safety data for the latter chemical has been relatively scarce particularly regarding potential damage to the kidney at low doses. Five-week-old ICR male mice were exposed to vehicle, DEHP or DINP (0.05 and 4.8 mg/kg bw) daily via gavage for 5 weeks. We observed increased levels of reactive oxygen species and malondialdehyde, decreased levels of reduced glutathione, in the kidney at higher dose for both chemicals suggestive of oxidative damage. Elevated levels of inflammatory cytokines tumor necrosis factor-α and interleukin-6 of the kidney further suggested inflammatory status as a result of phthalate exposure in both high dose groups. Targeted lipidomics demonstrated greatest changes in the kidney induced by high dose of DEHP, although DINP also induced significant changes in phospholipids diacylglycerides that are associated with lipid accumulation in glomerular podocytes and inflammatory responses. Our data suggest that oxidative stress may be involved in both DEHP- and DINP-induced renal lipidomic disruption and continue to question the suitability of DINP as proper DEHP substitute.


Assuntos
Dietilexilftalato , Ácidos Ftálicos , Animais , Dietilexilftalato/toxicidade , Rim , Lipidômica , Masculino , Camundongos , Camundongos Endogâmicos ICR , Estresse Oxidativo , Ácidos Ftálicos/toxicidade
9.
BMC Endocr Disord ; 21(1): 49, 2021 Mar 16.
Artigo em Inglês | MEDLINE | ID: mdl-33726721

RESUMO

BACKGROUND: As the incidence of secretory osteoporosis has increased, bone loss, osteoporosis and their relationships with thyroid-stimulating hormone (TSH) have received increased attention. In this study, the role of TSH in bone metabolism and its possible underlying mechanisms were investigated. METHODS: We analyzed the serum levels of free triiodothyronine (FT3), free thyroxine (FT4), and TSH and the bone mineral density (BMD) levels of 114 men with normal thyroid function. In addition, osteoblasts from rat calvarial samples were treated with different doses of TSH for different lengths of time. The related gene and protein expression levels were investigated. RESULTS: A comparison of the BMD between the high-level and low-level serum TSH groups showed that the TSH serum concentration was positively correlated with BMD. TSH at concentrations of 10 mU/mL and 100 mU/mL significantly increased the mRNA levels of ALP, COI1 and Runx2 compared with those of the control (P < 0.05, P < 0.01). Bone morphogenetic protein (BMP)2 activity was enhanced with both increased TSH concentration and increased time. The protein levels of Runx2 and osterix were increased in a dose-dependent manner. CONCLUSIONS: The circulating concentrations of TSH and BMD were positively correlated with normal thyroid function in males. TSH promoted osteoblast proliferation and differentiation in rat primary osteoblasts.

10.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 38(3): 210-213, 2021 Mar 10.
Artigo em Chinês | MEDLINE | ID: mdl-33751526

RESUMO

OBJECTIVE: To assess the value of chromosomal microarray analysis (CMA) for fetal duodenal obstruction (DO). METHODS: Fifty-one fetuses with DO identified by prenatal ultrasound were divided into DO only group and DO with other anomaly group. CMA was carried out on amniotic fluid or umbilical blood samples, and the outcome of pregnancy of all cases were followed up. RESULTS: Eight fetuses (15.7%) were found with genomic abnormalities, which included 3 chromosomal aneuploidies and 5 copy number variations (CNVs), including one 17q12 microduplication syndrome, one 13q21.33q31.1 microdeletion, one 13q21.32q22.3 deletion, one 13q21.2q31.1 deletion and one 1q43q44 duplication. EDNRB from 13q and HNF1B from 17q12 are candidate genes for fetal DO. No significant difference was found in the detection rate of pathogenic CNVs between the DO only and DO with other anomaly groups (9.5% vs.11.1%, P> 0.05). There were 39 live borns, 1 stillbirth, and 11 artificial abortions (8 with abnormal CMA results). CONCLUSION: There is a correlation between fetal DO and abnormal copy number of the genome, for which prenatal diagnosis is necessary. CMA not only can detect microdeletions/microduplications, but also identify pathogenic genes, which can facilitate prenatal diagnosis, genetic counseling and prognosis for the fetus.


Assuntos
Aberrações Cromossômicas , Variações do Número de Cópias de DNA , Obstrução Duodenal , Obstrução Duodenal/genética , Feminino , Feto , Humanos , Análise em Microsséries , Gravidez , Diagnóstico Pré-Natal
11.
Int J Stroke ; : 17474930211006301, 2021 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-33724094

RESUMO

BACKGROUND: Urinary and fecal incontinence are disabling impairments after stroke that can be clinically managed with electrical stimulation. AIM: The purpose of this systematic review was to determine the effectiveness of non-implanted electrical stimulation to reduce the severity of post-stroke incontinence. SUMMARY OF REVIEW: Clinical trials of non-implanted electrical stimulation applied for the purposes of treating post-stroke incontinence were searched in MEDLINE, EMBASE, CINAHL, PEDro, and CENTRAL. From a total of 5043 manuscripts, 10 trials met the eligibility criteria (n = 894 subjects). Nine trials reported urinary incontinence severity outcomes enabling meta-analysis of transcutaneous electrical nerve stimulation (TENS; five trials) and electroacupuncture (four trials). Studies provide good-to-fair quality evidence that TENS commenced <3 months post-stroke has a large effect on urinary continence (SMD = -3.40, 95% CI -4.46 to -2.34) and a medium effect when commenced >3 months after stroke (SMD = -0.67, 95% CI -1.09 to -0.26). Electroacupuncture has a large effect when administered >5 times a week (SMD = -2.32, 95% CI -2.96 to -1.68) and a small effect when administered five times a week (SMD = -0.44, 95% CI -0.69 to -0.18). Only one trial reported the effect of non-implanted electrical stimulation on post-stroke fecal incontinence. CONCLUSIONS: Published trials evaluating the effect of non-implanted electrical stimulation on post-stroke incontinence are few and heterogenous. Synthesized trials suggest that early and frequent treatment using electrical stimulation is probably more effective than sham or no treatment. Further trials measuring incontinence in an objective manner are required.

12.
Hum Mol Genet ; 2021 Feb 09.
Artigo em Inglês | MEDLINE | ID: mdl-33564857

RESUMO

The potentially different genetics and epigenetics in the primary tumors and metastases affect the efficacy of treatment in breast cancer patients. Nevertheless, the cellular and molecular mechanisms of breast cancer lymph node metastasis still remain elusive. Here, we employed single-cell RNA sequencing (scRNA-seq) to acquire the transcriptomic profiles of individual cells from primary tumours, negative, and positive lymph nodes. We also performed a single-cell assay for transposase-accessible chromatin (ATAC) sequencing (scATAC-seq) of the positive and negative lymph node samples to get the chromatin accessibility profile. We identified a novel cell subpopulation with an abnormally high expression level of CXCL14 in the positive lymph node of breast cancer patients. Cell trajectory analysis also revealed that CXCL14 was increased expressed in the late pseudo-time. Moreover. Based on a tissue microarray of 55 patients and the Oncomine database, We validated that CXCL14 expression was significantly higher in breast cancer patients with lymph node metastasis. Furthermore, scATAC-seq identified several transcription factors (TFs) that may be potential regulation factors for the lymph node metastasis of breast cancer. Thus, our findings will improve our current understanding of the mechanism for lymph node metastasis, and are potentially valuable in providing novel prognosis markers for lymphatic metastasis of breast cancer.

13.
Soft Matter ; 2021 Feb 04.
Artigo em Inglês | MEDLINE | ID: mdl-33538750

RESUMO

Based on the widely studied poly(l-lactic acid) (PLLA) and polyethylene terephthalate (PET) that are brittle in their fully crystalline form, this Letter shows that they can be made to be super ductile, heat resistant and optically clear by creating nano-sized crystals while preserving the entanglement network. Atomic force microscopic images confirm the perceived nano-confined crystallization. Time-resolved X-ray scattering/diffraction measurements reveal the emergence of cold crystallization during either stress relaxation from large stepwise melt-stretching or annealing of pre-melt-stretched PLLA and PET above Tg. Mechanical tests show that these polymers in such a new state are rigid even well above Tg, e.g., at 100 °C.

14.
Aging (Albany NY) ; 13(3): 4199-4214, 2021 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-33461171

RESUMO

Long non-coding RNAs are important regulators of biological processes, but their roles in the osteogenic differentiation of mesenchymal stem cells (MSCs) remain unclear. Here we investigated the role of murine HOX transcript antisense RNA (mHotair) in BMP9-induced osteogenic differentiation of MSCs using immortalized mouse adipose-derived cells (iMADs). Touchdown quantitative polymerase chain reaction analysis found increased mHotair expression in bones in comparison with most other tissues. Moreover, the level of mHotair in femurs peaked at the age of week-4, a period of fast skeleton development. BMP9 could induce earlier peak expression of mHotair during in vitro iMAD osteogenesis. Silencing mHotair diminished BMP9-induced ALP activity, matrix mineralization, and expression of osteogenic, chondrogenic and adipogenic markers. Cell implantation experiments further confirmed that knockdown of mHotair attenuated BMP9-induced ectopic bone formation and mineralization of iMADs, leading to more undifferentiated cells. Crystal violet staining and cell cycle analysis revealed that silencing of mHotair promoted the proliferation of iMAD cells regardless of BMP9 induction. Moreover, ectopic bone masses developed from mHotair-knockdown iMAD cells exhibited higher expression of PCNA than the control group. Taken together, our results demonstrated that murine mHotair is an important regulator of BMP9-induced MSC osteogenesis by targeting cell cycle and proliferation.

15.
Nurs Crit Care ; 26(2): 94-101, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33448567

RESUMO

BACKGROUND: Nurses are experiencing tremendous stress during the new coronavirus disease 2019 (COVID-19) pandemic, especially intensive care nurses. The pandemic of the disease is a tragedy, which may leave a catastrophic psychological imprint on nurses. Understanding nurses' mental distress can help when implementing interventions to mitigate psychological injuries to nurses. AIMS AND OBJECTIVES: To quantify the severity of nurses' post-traumatic stress disorder (PTSD) symptoms and stress and explore the influencing factors of their psychological health when caring for patients with COVID-19. DESIGN: A cross-sectional survey. METHODS: The PTSD Checklist-Civilian and the Perceived Stress Scale were administered from 11 to 18 March 2020, to 90 nurses selected from another city to go and help an intensive care unit (ICU) in Wuhan, China. These nurses were selected because of their high levels of clinical performance and resilience status. RESULTS: Nurses' average PTSD score was 24.62 ± 6.68, and five (5.6%) of the nurses reported a clinically significant level of PTSD symptoms (>38 points). Nurses' perceived stress averaged 19.33 ± 7, and 20 nurses (22.22%) scored positively >25 points. Nurses' stress and PTSD symptoms were positively correlated (P < .01). Major stress sources included working in an isolated environment, concerns about personal protective equipment shortage and usage, physical and emotional exhaustion, intensive workload, fear of being infected, and insufficient work experiences with COVID-19. CONCLUSIONS: This study showed that even relatively highly resilient nurses experienced some degree of mental distress, including PTSD symptoms and perceived stress. Our findings highlight the importance of helping nurses cultivate resilience and reduce stress. RELEVANCE TO CLINICAL PRACTICE: Recommendations for practice include providing adequate training and orientation before assigning nurses to ICU to help, offering disaster-emergency-preparedness training to keep nurses prepared, providing caring and authentic nursing leadership, offering ongoing psychological support to frontline nurses.


Assuntos
/enfermagem , Recursos Humanos de Enfermagem no Hospital/psicologia , Estresse Ocupacional/epidemiologia , Transtornos de Estresse Pós-Traumáticos/epidemiologia , Adulto , China/epidemiologia , Enfermagem de Cuidados Críticos , Estudos Transversais , Feminino , Humanos , Masculino , Recursos Humanos de Enfermagem no Hospital/estatística & dados numéricos , Fatores de Risco , Adulto Jovem
16.
Biosci Rep ; 41(1)2021 Jan 29.
Artigo em Inglês | MEDLINE | ID: mdl-33393627

RESUMO

The excessive and inappropriate production of reactive oxygen species (ROS) can cause oxidative stress and is implicated in the pathogenesis of lung cancer. Cyclophilin A (CypA), a member of the immunophilin family, is secreted in response to ROS. To determine the role of CypA in oxidative stress injury, we investigated the role that CypA plays in human lung carcinoma (A549) cells. Here, we showed the protective effect of human recombinant CypA (hCypA) on hydrogen peroxide (H2O2)-induced oxidative damage in A549 cells, which play crucial roles in lung cancer. Our results demonstrated that hCypA substantially promoted cell viability, superoxide dismutase (SOD), glutathione (GSH), and GSH peroxidase (GSH-Px) activities, and attenuated ROS and malondialdehyde (MDA) production in H2O2-induced A549 cells. Compared with H2O2-induced A549 cells, Caspase-3 activity in hCypA-treated cells was significantly reduced. Using Western blotting, we showed that hCypA facilitated Bcl-2 expression and inhibited Bax, Caspase-3, Caspase-7, and PARP-1 expression. Furthermore, hCypA activates the PI3K/Akt/mTOR pathway in A549 cells in response to H2O2 stimulation. Additionally, peptidyl-prolyl isomerase activity was required for PI3K/Akt activation by CypA. The present study showed that CypA protected A549 cells from H2O2-induced oxidative injury and apoptosis by activating the PI3K/Akt/mTOR pathway. Thus, CypA might be a potential target for lung cancer therapy.

17.
Theranostics ; 11(6): 3000-3016, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33456585

RESUMO

N6-methyladenosine (m6A) RNA modification, a dynamic and reversible process, is essential for tissue development and pathogenesis. However, the potential involvement of m6A in the regulation of cardiomyocyte (CM) proliferation and cardiac regeneration remains unclear. In this study, we aimed to investigate the essential role of m6A modification in heart regeneration during postnatal and adult injury. Methods and results: In this study, we identified the downregulation of m6A demethylase ALKBH5, an m6A "eraser" that is responsible for increased m6A methylation, in the heart after birth. Notably, ALKBH5 knockout mice exhibited decreased cardiac regenerative ability and heart function after neonatal apex resection. Conversely, forced expression of ALKBH5 via adeno-associated virus-9 (AAV9) delivery markedly reduced the infarct size, restored cardiac function and promoted CM proliferation after myocardial infarction in juvenile (7 days old) and adult (8-weeks old) mice. Mechanistically, ALKBH5-mediated m6A demethylation improved the mRNA stability of YTH N6-methyladenosine RNA-binding protein 1 (YTHDF1), thereby increasing its expression, which consequently promoted the translation of Yes-associated protein (YAP). The modulation of ALKBH5 and YTHDF1 expression in human induced pluripotent stem cell-derived cardiomyocytes consistently yielded similar results. Conclusion: Taken together, our findings highlight the vital role of the ALKBH5-m6A-YTHDF1-YAP axis in the regulation of CMs to re-enter the cell cycle. This finding suggests a novel potential therapeutic strategy for cardiac regeneration.

18.
J Hazard Mater ; 408: 124978, 2021 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-33385729

RESUMO

Mesoporous melamine-silver (MA-Ag) nanocomposites doped with carbon nitride quantum dots (CNQDs) were fabricated simply by the controlled supramolecular self-assembly. It was discovered that the resulting nanoflower-like CNQDs@MA-Ag nanocomposites could exhibit the peroxidase-like catalysis, which could be specifically enhanced by Hg2+ by forming Ag@Hg alloys. A double catalysis-based colorimetric method was thereby developed for the fast detecting of Hg2+ and Hg0 in wastewater samples, with the levels down to 0.050 nM and 18.3 nM, respectively. Moreover, strong visible-light-driven photocatalysis of the nanocomposites was demonstrated for oxidizing Hg0 into Hg2+ through photocatalytic H2O2 production so as to realize the detoxification of Hg0 in the environmental wastewater. Besides, the fabricated mesoporous CNQDs@MA-Ag nanocomposites with large specific surface areas might facilitate the high Hg adsorption through the powerful MA-Hg chelate interaction, showing the efficient adsorption and/or removal of total Hg. The catalysis-selective colorimetric analysis and photocatalysis-based detoxification removal of total mercury may promise for wide applications in the environmental monitoring and wastewater treatment of toxic heavy metals of mercury.

19.
Pharmacol Res ; 165: 105444, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33493657

RESUMO

With the development of high-throughput screening and bioinformatics technology, natural products with a range of pharmacological targets in multiple diseases have become important sources of new drug discovery. These compounds are derived from various plants, including the dried root of Scutellaria baicalensis Georgi, which is often used as a traditional Chinese herb named Huangqin, a popular medication used for thousands of years in China. Many studies have shown that baicalin, an extract from Scutellaria baicalensis Georgi, exerts various protective effects on liver and gut diseases. Baicalin plays a therapeutic role mainly by mediating downstream apoptosis and immune response pathways induced by upstream oxidative stress and inflammation. During oxidative stress regulation, PI3K/Akt/NRF2, Keap-1, NF-κB and HO-1 are key factors associated with the healing effects of baicalin on NAFLD/NASH, ulcerative colitis and cholestasis. In the inflammatory response, IL-6, IL-1ß, TNF-α, MIP-2 and MIP-1α are involved in the alleviation of NAFLD/NASH, cholestasis and liver fibrosis by baicalin, as are TGF-ß1/Smads, STAT3 and NF-κB. Regarding the apoptosis pathway, Bax, Bcl-2, Caspase-3 and Caspase-9 are key factors related to the suppression of hepatocellular carcinoma and attenuation of liver injury and colorectal cancer. In addition to immune regulation, PD-1/PDL-1 and TLR4-NF-κB are correlated with the alleviation of hepatocellular carcinoma, ulcerative colitis and colorectal cancer by baicalin. Moreover, baicalin regulates intestinal flora by promoting the production of SCFAs. Furthermore, BA is involved in the interactions of the liver-gut axis by regulating TGR5, FXR, bile acids and the microbiota. In general, a comprehensive analysis of this natural compound was conducted to determine the mechanism by which it regulates bile acid metabolism, the intestinal flora and related signaling pathways, providing new insights into the pharmacological effects of baicalin. The mechanism linking the liver and gut systems needs to be elucidated to draw attention to its great clinical importance.

20.
Vet Microbiol ; 254: 108980, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33445054

RESUMO

The Caprine parainfluenza virus 3 (CPIV3) is a novel Paramyxovirus that is isolated from goats suffering from respiratory diseases. Presently, the pathogenesis of CPIV3 infection has not yet been fully characterized. The Type I interferon (IFN) is a key mediator of innate antiviral responses, as many viruses have developed strategies to circumvent IFN response, whether or how CPIV3 antagonizes type I IFN antiviral effects have not yet been characterized. This study observed that CPIV3 was resistant to IFN-α treatment and antagonized IFN-α antiviral responses on MDBK and goat tracheal epithelial (GTE) cell models. Western blot analysis showed that CPIV3 infection reduced STAT1 expression and phosphorylation, which inhibited IFN-α signal transduction on GTE cells. By screening and utilizing specific monoclonal antibodies (mAbs), three CPIV3 accessory proteins C, V and D were identified during the virus infection process on the GTE cell models. Accessory proteins C and V, but not protein D, was identified to antagonize IFN-α antiviral signaling. Furthermore, accessory protein C, but not protein V, reduced the level of IFN-α driven phosphorylated STAT1 (pSTAT1), and then inhibit STAT1 signaling. Genetic variation analysis to the PIV3 accessory protein C has found two highly variable regions (VR), with VR2 (31-70th aa) being involved in for the CPIV3 accessory protein C to hijack the STAT1 signaling activation. The above data indicated that CPIV3 is capable of inhibiting IFN-α signal transduction by reducing STAT1 expression and activation, and that the accessory protein C, plays vital roles in the immune escape process.

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