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1.
Artigo em Inglês | MEDLINE | ID: mdl-34745285

RESUMO

Objective: We conducted a systematic review and meta-analysis to evaluate the curative effect of probiotics combined with enteral nutrition (EN) in patients with stroke. Methods: We retrieved randomized controlled trials and case-controlled trials on the use of probiotics for stroke treatment from PubMed, Web of Science, CNKI, Wanfang, and Weipu databases. Retrieval times were from the databases' inception to November 6, 2020. Two researchers conducted a strict evaluation of the literature quality and extracted the data, which were then entered into RevMan 5.3 for meta-analysis. Results: Twenty-three articles were included, including 1,816 patients. The meta-analysis revealed that probiotics combined with EN did not reduce NIHSS scores of patients with stroke (P > 0.05). However, it did shorten hospital stays and bedrest periods (P < 0.05). Probiotics combined with EN also improved patients' nutritional status and increased hemoglobin, albumin, serum total protein, and physical and chemical properties of prealbumin (P < 0.05). In terms of relieving inflammation, we found that probiotics combined with EN reduced neither high-sensitivity C-reactive protein nor procalcitonin (P > 0.05). However, it did cause a significant reduction in TNF-α, IL-6, and IL-10. Probiotics combined with EN significantly reduced esophageal reflux, bloating, constipation, diarrhea, gastric retention, and gastrointestinal bleeding. It relieved intestinal stress and reduced the occurrence of adverse reactions such as esophageal reflux, bloating, constipation, diarrhea, gastric retention, and gastrointestinal bleeding (P < 0.05). In terms of reducing stroke complications, probiotics combined with EN reduced the incidence of lung, gastrointestinal, and urinary tract infections (P < 0.05). It also reduced fatality rates and intestinal flora imbalance rates (P < 0.05). Conclusion: The probiotics combined with EN group's therapeutic effects were superior to those of the EN alone. Thus, probiotics combined with EN is worthy of both clinical application and promotion in stroke treatment.

2.
Inorg Chem ; 2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34823356

RESUMO

The recent years have witnessed the glory development for the construction of high-performance mononuclear single molecule magnets (SMMs) within a specific coordination geometry, which, however, is not well applied in cluster-based SMMs due to the synthetic challenges. Given that the monocobalt(II) complexes within a trigonal-prismatic (TPR) coordination geometry have been classified as excellent SMMs with huge axial anisotropy (D ≈ -100 cm-1), here we designed and synthesized a new dual-capping tetrazine ligand, 3,6-bis(6-(di(1H-pyrazol-1-yl)methyl)pyridin-2-yl)-1,2,4,5-tetrazine (bpptz), and prepared a novel dicobalt(II) complex, [Cp2CoIII][{(hfac)CoII}2(bpptz•-)][hfac]2·2Et2O (1, hfac = hexafluoroacetylacetonate). In the structure of 1, the bpptz•- radical ligand enwraps two Co(II) centers within quasi-TPR geometries, which are further bridged by the tetrazine radical in the trans mode. The magnetic study revealed that the interaction between the Co centers and the tetrazine radical is strongly antiferromagnetic with a coupling constant (J) of -65.8 cm-1 (in the -2J formalism). Remarkably, 1 exhibited the typical SMM behavior with an effective energy barrier of 69 cm-1 under a 1.5 kOe dc field, among the largest for polynuclear transition metal SMMs. In addition, DFT and ab initio calculations suggested that the presence of a strong Co(II)-radical magnetic interaction effectively quenches the QTM effect and enhances the barrier height for the magnetization reversal.

3.
Clin Sci (Lond) ; 135(22): 2575-2588, 2021 Nov 26.
Artigo em Inglês | MEDLINE | ID: mdl-34779863

RESUMO

Maternal exposure to fine particulate matter (PM2.5) causes hypertension in offspring. However, paternal contribution of PM2.5 exposure to hypertension in offspring remains unknown. In the present study, male Sprague-Dawley rats were treated with PM2.5 suspension (10 mg/ml) for 12 weeks and/or fed with tap water containing an antioxidant tempol (1 mM/L) for 16 weeks. The blood pressure, 24 h-urine volume and sodium excretion were determined in male offspring. The offspring were also administrated with losartan (20 mg/kg/d) for 4 weeks. The expressions of angiotensin II type 1 receptor (AT1R) and G-protein-coupled receptor kinase type 4 (GRK4) were determined by qRT-PCR and immunoblotting. We found that long-term PM2.5 exposure to paternal rats caused hypertension and impaired urine volume and sodium excretion in male offspring. Both the mRNA and protein expression of GRK4 and its downstream target AT1R were increased in offspring of PM2.5-exposed paternal rats, which was reflected in its function because treatment with losartan, an AT1R antagonist, decreased the blood pressure and increased urine volume and sodium excretion. In addition, the oxidative stress level was increased in PM2.5-treated paternal rats. Administration with tempol in paternal rats restored the increased blood pressure and decreased urine volume and sodium excretion in the offspring of PM2.5-exposed paternal rats. Treatment with tempol in paternal rats also reversed the increased expressions of AT1R and GRK4 in the kidney of their offspring. We suggest that paternal PM2.5 exposure causes hypertension in offspring. The mechanism may be involved that paternal PM2.5 exposure-associated oxidative stress induces the elevated renal GRK4 level, leading to the enhanced AT1R expression and its-mediated sodium retention, consequently causes hypertension in male offspring.

4.
ANZ J Surg ; 2021 Nov 24.
Artigo em Inglês | MEDLINE | ID: mdl-34820987

RESUMO

INTRODUCTION: Renal ischemia-reperfusion injury (IRI) can lead to significant morbidity and mortality. It remains a leading cause of acute kidney injury and is therefore an important issue in trauma and renal transplant surgery. Various pharmaceutical agents have been used in an attempt to dampen the harmful effects of IRI but few have been shown to be useful clinically. Riluzole, Lidocaine and Lamotrigine have been demonstrated to show anti-ischaemic properties in other organs; however, their use has not been tested in the kidneys. We investigated Riluzole, Lidocaine and Lamotrigine for their preventive effects of renal IRI using a rat model. METHODS: Winstar rats (n = 48) were divided into four groups (n = 12 per group)-three treatment groups and one control group. Riluzole, Lidocaine and Lamotrigine were given prior to renal ischemia only (IO) or IRI. The degree of ischemia was measured by glutathione levels and a TUNEL assay was used to measure DNA fragmentation. RESULTS: Riluzole, Lidocaine and Lamotrigine pre-treatment each resulted in statistically higher glutathione levels compared to controls (P = 0.002; P = 0.007 and P = 0.005, respectively). Riluzole and Lidocaine were also effective at preventing depletion of glutathione following IO (P = 0.007 and P = 0.014 respectively), while Lamotrigine was ineffective in IO (P = 0.71). The degree of DNA fragmentation seen on the TUNEL assay was markedly reduced in all three-drug groups in both IO and IRI. DISCUSSION: Riluzole, Lidocaine and Lamotrigine all have anti-ischaemic effects in the rat kidney and can have potential therapeutic implications.

5.
Allergy Asthma Immunol Res ; 13(6): 863-881, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34734505

RESUMO

PURPOSE: The pathogenic mechanisms of antrochoanal polyps (ACPs) remain largely unknown. This study aimed to characterize inflammatory patterns and tissue remodeling features in ACPs. METHODS: Inflammatory cell infiltration and tissue edema severity as well as fibrin deposition in ACPs and bilateral eosinophilic and noneosinophilic nasal polyps (NPs) were studied with immunohistochemical and immunofluorescence staining. Cytokine levels in sinonasal tissues were detected with the Bio-Plex assay. The expression of coagulation and fibrinolytic markers was measured using reverse-transcription polymerase chain reaction and enzyme-linked immunosorbent assays. RESULTS: Compared to control tissues and bilateral eosinophilic and noneosinophilic NPs, ACPs had higher levels of neutrophil infiltration and expression of myeloperoxidase (MPO), interleukin (IL)-8 and interferon (IFN)-γ. In total, 94.4% of ACPs demonstrated an eosinophil cationic protein/MPO ratio of < 1, compared to 79.0% of noneosinophilic and 26% of eosinophilic NPs. Principle component and multiple correspondence analyses revealed a neutrophilic and type 1 inflammation pattern in ACPs. Compared to control tissues, edema scores and fibrin deposition were increased, whereas d-dimer and tissue plasminogen activator (tPA) levels were decreased in ACPs and bilateral NPs, with more prominent changes in ACPs even than in eosinophilic NPs. The tPA levels were negatively correlated with IFN-γ, IL-8, and MPO levels in ACPs. Neutrophils were the major cellular source of IFN-γ in ACPs, and the number of IFN-γ+ neutrophils was elevated in ACPs than in control tissues and bilateral eosinophilic and noneosinophilic NPs. CONCLUSIONS: ACPs are characterized by the neutrophilic and type 1 inflammation endotype. Neutrophil-derived IFN-γ is associated with reduced tPA production in ACPs.

6.
Membranes (Basel) ; 11(11)2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34832131

RESUMO

ZnO/ZnS nanocomposite-based nanostructures exhibit dual light and gas sensing capabilities. To further boost the light/dual sensing properties, gold nanoparticles (Au NPs) were incorporated into the core-shell structures. Multiple material characterizations revealed that Au NPs were successfully well spread and decorated on ZnO/ZnS nanostructures. Furthermore, our findings show that the addition of Au NPs could enhance both 365 nm UV light sensing and hydrogen gas sensing in terms of light/gas sensitivity and light/gas response time. We postulate that the optimization of gas/light dual sensing capability may result from the induced electric field and inhabitation of electron-hole recombination. Owing to their compact size, simple fabrication, and stable response, ZnO/ZnS/Au NPs-based light/gas dual sensors are promising for future extreme environmental monitoring.

7.
Arthroplast Today ; 11: 163-167, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34646921

RESUMO

As the numbers of arthroplasties performed worldwide increase, so do complications such as prosthetic joint infection. Cases that require a two-stage revision of a total femur replacement in the femur pose an ongoing challenge to the modern orthopedic surgeon. Unlike antibiotic spacers in hip and knee arthroplasty, there lacks a commercially available cement spacer for use in total femur replacements. We describe a novel technique for the intraoperative fabrication of a total femur spacer which uses modular components. As such, our technique is unique as it is modular and, therefore, highly customisable to each individual patient. Individual components can be made by different members of the team simultaneously and then assembled to make the final construct, thereby minimizing operative time. Furthermore, the inherent stability of the spacer allows immediate partial weightbearing and functional rehabilitation while patients are waiting for their second-stage procedure.

8.
Small ; : e2103993, 2021 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-34713567

RESUMO

Phototherapy has recently emerged as a competent alternative for combating bacterial infection without antibiotic-resistance risk. However, owing to the bacterial endogenous antioxidative glutathione (GSH), the exogenous reactive oxygen species (ROS) generated by phototherapy can hardly behave desired antibacterial effect. To address the daunting issue, a quad-channel synergistic antibacterial nano-platform of Ti3 C2 MXene/MoS2 (MM) 2D bio-heterojunctions (2D bio-HJs) are devised and fabricated, which possess photothermal, photodynamic, peroxidase-like (POD-like), and glutathione oxidase-like properties. Under near-infrared (NIR) laser exposure, the 2D bio-HJs both yield localized heating and raise extracellular ROS level, leading to bacterial inactivation. Synchronously, Mo4+ ions can easily invade into ruptured bacterial membrane, arouse intracellular ROS, and deplete intracellular GSH. Squeezed between the "ROS hurricane" from both internal and external sides, the bacteria are hugely slaughtered. After being further loaded with fibroblast growth factor-21 (FGF21), the 2D bio-HJs exhibit benign cytocompatibility and boost cell migration in vitro. Notably, the in vivo evaluations employing a mouse-infected wound model demonstrate the excellent photonic disinfection towards bacterial infection and accelerated wound healing. Overall, this work provides a powerful nano-platform for the effective regeneration of bacteria-invaded cutaneous tissue using 2D bio-HJs.

9.
J Gastrointest Oncol ; 12(4): 1797-1810, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532129

RESUMO

Background: To explore the potential biological function of XPA (Xeroderma pigmentosum group A) in hepatic neoplasms and the underlying molecular mechanisms. Methods: Liver cells were used as experimental models to establish HCC (hepatocellular carcinoma) in vitro. Protein extractions were subjected to Western blotting to detect the proteins expression. The lentivirus transfection efficiency was confirmed by Western blot and RT-qPCR, Tunnel staining was used to detect apoptosis, and Transwell assays were used to observe cell migration and invasion. Cell proliferation was detected with colony formation and CCK-8 (cell counting kit-8) assays. Results: XPA expression was obviously lower in HCC tissue and liver cancer cell lines. XPA overexpression induced autophagy and apoptosis by increasing LC3B II/I, Beclin1, cleaved-caspase-3, and Bax expression and decreasing p62 and Bcl2 protein levels. XPA also suppressed HCC EMT (Epithelial-Mesenchymal Transition) by increasing E-cadherin and decreasing N-cadherin and vimentin protein expression. Cell proliferation, migration and invasion in vivo were significantly inhibited by the overexpression of XPA, and p-PI3K, p-Akt, and p-mTOR expression were decreased in LV-XPA cells. In general, XPA inhibited HCC by inducing autophagy and apoptosis and by modulating the expression of PI3K/Akt/mTOR proteins. Conclusions: XPA overexpression was found to suppress HCC by inducing autophagy and apoptosis and repressing EMT and proliferation. Each of these effects may be involved in modulating the PI3K/Akt/mTOR signaling pathway.

10.
Inorg Chem ; 60(18): 14330-14335, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34491733

RESUMO

A family of molecular capsules, {[(Tp*)Fe(CN)3Co(bpyC═N(CH2)7N═Cbpy)]2[X]2}·sol (1, X = ClO4, sol = 6DMF; 2, X = PF6, sol = 6DMF; 3, X = OTf, sol = 6DMF; 4, X = BPh4, sol = 2DMF; Tp* = hydrotris(3,5-dimethylpyrazol-1-yl)borate; bpy = 2,2'-bipyridine), were prepared via the Schiff-base condensation of the aldehyde-substituted bpy (bpyCHO) and 1,7-diaminoheptane (H2N(CH2)7NH2). All the complexes contain the same cyanide-bridged cationic square cores ([Fe2Co2]2+), which are encapsuled by the flexible alkyl chains. Variable-temperature single-crystal X-ray diffraction, FT-IR spectra, and magnetic studies reveal the abrupt and complete, thermo- and photo-induced electron-transfer-coupled spin transition for 1-3, while the pure high-spin phase for 4. Such distinct behavior is attributed to the effective long-range cooperative interactions mediated by the intercluster π-π couplings in 1-3, which, however, are significantly blocked in 4 due to the steric effect of interstitial BPh4- anions. Furthermore, the shift in the thermally induced transition temperatures of 254 K for 1, 233 K for 2, and 187 K for 3, respectively, is likely correlated to the variable H···O and H···F interactions between the solvent molecules, anions, and the bipyridine ligands of the [Fe2Co2] squares, suggesting the significant anion-dependent effect in such a system.

12.
Dalton Trans ; 50(40): 14303-14308, 2021 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-34554167

RESUMO

The supramolecular self-assembly synthetic strategy provides a valid tool to obtain polynuclear Fe(II) complexes having effective communication between the metal centres and distinct spin crossover behaviour. Despite the great success in constructing various magnetic molecules, progress has not been made in SCO complexes based on azido bridges. In this article, the coordination-driven supramolecular assembly based on 3,6-substituted pyridazine and azide is presented to afford two Fe(II) grid-like complexes: [(L)4FeII4(N3)4][BPh4]4·sol (1, L = 3,6-bis(3,5-dimethyl-1H-pyrazol-1-yl)pyridazine and 2, L = 3,6-di(pyridin-2-yl)pyridazine). The substitution of pyridinyl groups in 2 instead of pyrazolyl ones in 1 led to the only example exhibiting spin-crossover behaviour (T1/2 = 230 K) among the azido-bridged complexes. In addition, a temperature-dependent photoluminescence study of 2 demonstrates a visible synergetic effect between the SCO event and the luminescence.

13.
Front Pharmacol ; 12: 746910, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34539419

RESUMO

Hand-foot syndrome (HFS) is a common capecitabine-based chemotherapy-related adverse event (CRAE) in patients with colorectal cancer (CRC). It is of great significance to comprehensively identify susceptible factors for HFS, and further to elucidate the biomolecular mechanism of HFS susceptibility. We performed an untargeted multi-omics analysis integrating DNA methylation, transcriptome, and metabolome data of 63 Chinese CRC patients who had complete CRAE records during capecitabine-based chemotherapy. We found that the metabolome changes for each of matched plasma, urine, and normal colorectal tissue (CRT) in relation to HFS were characterized by chronic tissue damage, which was indicated by reduced nucleotide salvage, elevated spermine level, and increased production of endogenous cytotoxic metabolites. HFS-related transcriptome changes of CRT showed an overall suppressed inflammation profile but increased M2 macrophage polarization. HFS-related DNA methylation of CRT presented gene-specific hypermethylation on genes mainly for collagen formation. The hypermethylation was accumulated in the opensea and shore regions, which elicited a positive effect on gene expression. Additionally, we developed and validated models combining relevant biomarkers showing reasonably good discrimination performance with the area under the receiver operating characteristic curve values from 0.833 to 0.955. Our results demonstrated that the multi-omics variations associated with a profibrotic phenotype were closely related to HFS susceptibility. HFS-related biomolecular variations in CRT contributed more to the relevant biomolecular mechanism of HFS than in plasma and urine. Spermine-related DNA hypermethylation and elevated expression of genes for collagen formation were closely associated with HFS susceptibility. These findings provided new insights into the susceptible factors for chemotherapy-induced HFS, which can promote the implementation of individualized treatment against HFS.

14.
Anal Chem ; 93(37): 12655-12663, 2021 09 21.
Artigo em Inglês | MEDLINE | ID: mdl-34476942

RESUMO

Metal wires have been used as an alternative to liquid junctions for the connection of solutions in microfabricated electrochemical devices. They exhibit similar performance to liquid junctions, provided that the interfacial potentials at both ends of the wires were appropriately canceled. Cyclic voltammograms of devices with liquid junctions and metal wires were very similar when no current or a low current flowed through the metal wire between the working and reference electrodes. Iridium wires with iridium oxide at both ends facilitated canceling of the interfacial potentials at either end of the junction particularly well, and were used effectively for voltammetry, amperometry, and potentiometry by adjusting the pH of the solutions in the working and reference electrode compartments to be equal. This approach was used to effectively integrate a reliable common reference electrode between multiple working electrodes and to conduct automated electrochemical control of solution transport in microfluidic systems.


Assuntos
Técnicas Biossensoriais , Eletrodos , Potenciometria
15.
Fish Shellfish Immunol ; 118: 213-218, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34517139

RESUMO

Apoptosis plays essential roles in the immune defense mechanism against pathogen infection. Caspase 3 is a family of cysteine proteases involved in apoptosis and the immune response. In this study, the full-length of mud crab (Scylla paramamosain) caspase 3 (designated as Sp-caspase 3) was cloned and characterized. The open reading frame of Sp-caspase 3 was comprised a 1035 bp, which encoded a putative protein of 344 amino acids. Sp-caspase 3 was ubiquitously expressed in various tissues with a high-level expression in hemocytes. Cellular localization analysis revealed that Sp-caspase 3 was located in the cytoplasm and nucleus. Over-expression of Sp-caspase 3 could induce cell apoptosis. In addition, V. Parahaemolyticus infection induced the relative expression of caspase-3 mRNA and increased caspase-3 activity. Knocking down Sp-caspase 3 in vivo significantly reduced cell apoptosis and increased mortality of mud crab after V. parahaemolyticus infection. These results indicated that Sp-caspase 3 played important roles in the immune response and apoptosis against bacterial infection.

16.
Int J Med Robot ; 17(6): e2333, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34533876

RESUMO

BACKGROUND: Recently, thymectomy using minimally invasive approaches has been increasing with the development of robotic video-assisted thoracoscopic surgery (R-VATS). Although multimodal approach is effective for robot assisted thymectomy, it is necessary to determine the approach (left, right or subxiphoid) associated with the least complications. METHODS: An electronic retrieval from PubMed, Embase, Web of Science, GreyNet International and The Cochrane Library. The single-arm meta-analysis was performed to compare the rate of complications of right- and left-side approaches by R-VATS. RESULTS: A total of 21 studies including 930 patients were identified. The pooled incidence of total complications was 12.2% (confidence interval: 10.0%-14.8%) for all studies. The overall complication rate was 17.3% for the right-side compared with 7.4% for the left side (P < 0.001, odds ratio = 2.484, 1.601-3.852). The pooled incidence of air leak was significantly higher for the right versus left side (5.1% vs. 1.2%, respectively; p = 0.004). The incidence of atrial fibrillation was higher for the right-side compared with the left-side approach (4% vs. 1.2%, respectively; p = 0.004). The open conversion rate was significantly higher for the right versus the left-side (6.5% vs. 2.9%, respectively; p = 0.004). However, there was no significant difference in the pooled incidence of pleural effusion and thoracic duct fistula when comparing the right- and left-side approaches. In subgroup analysis, in the left approach, the incidence of overall complications (28.6% vs. 5.5%, respectively; p = 0.002) and pleural effusion (14.3% vs. 1%, respectively; p = 0.002) was higher for the 'Old Age' group compared with the 'Youth' group; However, In the subgroup analysis of gender, there was no significant difference in the incidence of complications after thymectomy. CONCLUSION: Robotic video-assisted thoracoscopic surgery can be performed on the left- and right-sides; however, complications are minimal with the left-side approach. These data demonstrate that the incidence of overall complications, atrial fibrillation, open conversion ratios, and air leak rate of left-side R-VATS thymectomy are lower than those of right-side. Further subgroup analysis showed that the incidence of postoperative complications was higher in the older group.


Assuntos
Robótica , Timectomia , Adolescente , Humanos , Complicações Pós-Operatórias/etiologia , Cirurgia Torácica Vídeoassistida , Timectomia/efeitos adversos , Resultado do Tratamento
17.
J Integr Plant Biol ; 2021 Sep 27.
Artigo em Inglês | MEDLINE | ID: mdl-34570416

RESUMO

Flavonoids are polyphenolic secondary metabolites that function as signaling molecules, allopathic compounds, phytoalexins, detoxifying agents and antimicrobial defensive compounds in plants. Blast caused by the fungus Magnaporthe oryzae is a serious disease affecting rice cultivation. In this study, we revealed that a natural flavonoid, tangeretin, substantially delays the formation of M. oryzae appressoria and blocks the development of blast lesions on rice plants. Our data suggest that tangeretin has antioxidant activity that interferes with conidial cell death/ferroptosis, which is critical for M. oryzae pathogenicity. Tangeretin showed a ferroptosis inhibition efficacy comparable to the well-established liproxstatin-1. Furthermore, overexpression of the NADPH oxidases NOX1 or NOX2 significantly decreased sensitivity toward tangeretin treatment, suggesting Nox-mediated lipid peroxidation as a possible target for tangeretin in regulating redox signaling and ferroptosis in M. oryzae. Our nursery and field tests showed that application of tangeretin can effectively mitigate overall disease symptoms and prevent leaf blast. Our study reveals the plant-derived fungal ferroptosis inhibitor tangeretin as a potential and novel antifungal agrochemical for the sustainable prevention of the devastating blast disease in important cereal crops.

18.
J Virol ; 95(24): e0126721, 2021 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-34586866

RESUMO

Introduction of non-pharmaceutical interventions to control COVID-19 in early 2020 coincided with a global decrease in active influenza circulation. However, between July and November 2020, an influenza A(H3N2) epidemic occurred in Cambodia and in other neighboring countries in the Greater Mekong Subregion in Southeast Asia. We characterized the genetic and antigenic evolution of A(H3N2) in Cambodia and found that the 2020 epidemic comprised genetically and antigenically similar viruses of Clade3C2a1b/131K/94N, but they were distinct from the WHO recommended influenza A(H3N2) vaccine virus components for 2020-2021 Northern Hemisphere season. Phylogenetic analysis revealed multiple virus migration events between Cambodia and bordering countries, with Laos PDR and Vietnam also reporting similar A(H3N2) epidemics immediately following the Cambodia outbreak: however, there was limited circulation of these viruses elsewhere globally. In February 2021, a virus from the Cambodian outbreak was recommended by WHO as the prototype virus for inclusion in the 2021-2022 Northern Hemisphere influenza vaccine. IMPORTANCE The 2019 coronavirus disease (COVID-19) pandemic has significantly altered the circulation patterns of respiratory diseases worldwide and disrupted continued surveillance in many countries. Introduction of control measures in early 2020 against Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) infection has resulted in a remarkable reduction in the circulation of many respiratory diseases. Influenza activity has remained at historically low levels globally since March 2020, even when increased influenza testing was performed in some countries. Maintenance of the influenza surveillance system in Cambodia in 2020 allowed for the detection and response to an influenza A(H3N2) outbreak in late 2020, resulting in the inclusion of this virus in the 2021-2022 Northern Hemisphere influenza vaccine.

19.
Front Pharmacol ; 12: 689111, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34366846

RESUMO

Nonalcoholic fatty liver disease (NAFLD) results from an abnormal accumulation of lipids within hepatocytes, and is commonly associated with obesity, insulin resistance, and hyperlipidemia. Metformin is commonly used to treat type 2 diabetes mellitus and, in recent years, it was found to play a potential role in the amelioration of NAFLD. However, the mechanisms underlying the protective effect of metformin against NAFLD remain largely unknown. Transcription factor EB (TFEB) is a master transcriptional regulator of lysosomal biogenesis and autophagy and, when activated, is effective against disorders of lipid metabolism. However, the role of TFEB in hepatic steatosis is not well understood. In this report, we demonstrate that the activity of TFEB is reduced in the liver of mice fed a high-fat diet. Metformin treatment significantly reverses the activity of TFEB, and the protective effect of metformin against hepatic steatosis and insulin resistance is dependent on TFEB. We show that metformin-induced autophagy is regulated by TFEB, and our findings reveal that TFEB acts as a mediator, linking metformin with autophagy to reverse NAFLD, and highlight that TFEB may be a promising molecular target for the treatment of NAFLD.

20.
Curr Med Sci ; 41(4): 803-814, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34403106

RESUMO

OBJECTIVE: Autophagy was prominently activated by cerebral ischaemia. This study was to investigate the exact role of autophagy in ischaemic stroke. METHODS: Two rat models of transient middle cerebral artery occlusion (tMCAO) and permanent MCAO (pMCAO) were prepared. The brain tissues in the penumbra were obtained to observe the dynamic variations of autophagy activity with Beclin1 and LC3 antibodies by Western blotting. At the characteristic time points, when autophagy activity was markedly elevated or reduced, the autophagy activation signaling was intervened with rapamycin and 3-methyladenine, respectively. Thereafter, key proteins in the autopahgic/lysosomal pathway were detected with the antibodies of LC3, p62, ubiquitin, LAMP-1 and cathepsin B. Meanwhile, TTC staining, neurological score and immunofluorescence were performed to evaluate brain infarct volume, neurological deficit and neuron survival, respectively. RESULTS: Both Beclin1 and LC3 expression levels were remarkably altered at 6 h, 12 h, 2 days and 7 days after tMCAO. Interestingly, the dynamic changes of autophagy activity following pMCAO were identical to those after tMCAO. Neither autophagy induction nor autophagy inhibition was able to ameliorate the pMCAO-induced neurological injury due to lysosomal dysfunction, as indicated by low levels of LAMP-1 and cathepsin B, accompanied with the accumulation of LC3-II, ubiquitin and insoluble p62. Comparatively, autophagy induction elicited overt neuroprotection at 2 and 7 days after tMCAO, and this neuroprotection might be elicited by the enhancement of autophagy flux. CONCLUSION: Our study suggests that autophagy confers neuroprotection at the subacute phase of tMCAO but has few effects on neurological outcomes after pMCAO.

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