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1.
J Tradit Chin Med ; 41(1): 59-67, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33522198

RESUMO

OBJECTIVE: To evaluate the anti-apoptotic efficacy of Qingnao Yizhi formula (,QNYZ) in cultured cerebral cortical neuronal cells (CNCs) and the regulation of the NogoA-Nogo receptor (NgR)/Rho-Rho kinase (ROCK) signaling pathway. METHODS: Primary cultured CNCs were randomly divided into the following groups: normal control group (N-C), hypoxia-reoxygenation group (H/R), high-dose QNYZ group (Q-H), low-dose QNYZ group (Q-L) butylphthalide (NBP) group, and Y-27632 (a selective ROCK transduction pathway inhibiter) group. Except those in the N-C group, CNCs were placed in hypoxic conditions for 24 h and then in reoxygenation conditions for 24 h. Cell media was changed every 48 h, and various assays were performed on the 7th day. Cell viability was evaluated by measuring mitochondrial dehydrogenase activity, using a CCK-8 assay, in triplicate. Synapsin (SYN) protein concentrations were evaluated by enzyme-linked immunosorbent assay. NogoA and RhoA protein expression were evaluated through Western blotting. The gene expression of NogoA, NgR, RhoA, and ROCK was evaluated by reverse transcription-polymerase chain reaction. Cell apoptosis was measured using a terminal deoxynucleotidyl transferase biotin-dUTP nick end labeling assay. RESULTS: Compared with the N-C group, the cell viability of the H/R group decreased significantly (P < 0.05). The cell viability values for the Q-H and Q-L groups increased compared with that for the H/R group, and the difference was significant for the Q-H group (P < 0.05). The NogoA and RhoA protein levels and the NogoA, NgR, RhoA, and ROCK mRNA expression levels increased in the H/R group, compared with the N-C group, and decreased significantly in the Q-H and Q-L groups (P < 0.05) and in the Y-27632 group (P < 0.05) compared with the H/R group. The SYN levels in the Q-H, Q-L, and NBP groups significantly increased compared with that in the H/R group (P < 0.05). Compared with the H/R group, the numbers of apoptotic cells in the Q-H, Q-L, and NBP groups significantly decreased (P < 0.05). CONCLUSION: The presented study demonstrated that QNYZ exerted anti-apoptotic effects on H/R-induced CNCs, possibly through the modulation of the NogoA-NgR/Rho-ROCK signaling pathway and the promotion of synaptic plasticity in H/R CNCs.

2.
Hypertens Res ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33603172

RESUMO

Appropriate body posture is important for accurate blood pressure (BP) measurement. However, the impact of an unsupported back on BP readings is currently controversial. This study included 224 subjects (18-86 years old, 54.5 ± 15.5 years old, 105 males). BP was measured with an oscillometric BP device randomly following one of two protocols for back support conditions: (1) supported-unsupported-supported-unsupported, or (2) unsupported-supported-unsupported-supported. The average of the two systolic BP (SBP) and diastolic BP (DBP) readings in the same position was recorded as the final BP value. The differences in BP between the unsupported and supported back conditions were calculated as delta BP. Moreover, the percentage variation in BP (PV) was calculated with the formula delta BP/BP with an unsupported back. Multivariable regression analysis evaluated the impact of age, sex, hypertension history and supported BP level on PV. The SBP/DBP levels measured with an unsupported back were slightly higher than those when the back was supported (132.7 ± 19.5/79.6 ± 12.9 mmHg vs. 130.3 ± 20.0/78.5 ± 14.3 mmHg), and the delta SBP (2.3 mmHg) was statistically significant. The multivariable regression analysis showed that age was a positive factor but supported SBP level as a negative factor for systolic PV, while age and supported DBP level were positive factors, but hypertension history was a negative factor for diastolic PV. For a group participant, the mean difference in oscillometric SBP/DBP in the unsupported back position was 2.3/1.0 mmHg higher than that in the supported back position.

3.
Conserv Biol ; 2021 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-33595149

RESUMO

Species monitoring, defined here as the repeated, systematic collection of data to detect long-term changes in the populations of wild species, is a vital component of conservation practice and policy. We created a database of nearly 1,200 schemes to review spatial, temporal, taxonomic and methodological patterns in global species monitoring. We estimate the total global number of monitoring schemes operating at 3,300-15,000. Since 2000 there has been a sharp increase in the number of new schemes being initiated in lower- and middle-income countries and in megadiverse countries, but a fall in high-income countries. Our review found a strong positive correlation between the total number of monitoring schemes in a country and its per capita GDP. Schemes that were active in 2018 had been running for an average of 21 years in high-income countries, compared with 13 years in middle-income countries and 10 years in low-income countries. In high-income countries, over half of monitoring schemes receive government funding, but this falls to less than a quarter in low-income countries. Data collection is undertaken partly or wholly by volunteers in 37% of schemes, and such schemes cover significantly more sites and species than those undertaken by professionals alone. Birds were by far the most widely monitored taxonomic group, accounting for around half of all schemes, but this bias has declined over time. Monitoring in most taxonomic groups remains very sparse and uncoordinated, and most of the data generated are elusive and unlikely to feed into wider biodiversity conservation processes. We propose ways in which these shortcomings could be addressed, especially by creating an open global meta-database of biodiversity monitoring schemes and enhancing capacity for species monitoring in countries with high biodiversity. Article impact statement: Species population monitoring for conservation purposes remains strongly biased toward a few vertebrate taxa in wealthier countries. This article is protected by copyright. All rights reserved.

4.
Acta Pharmacol Sin ; 42(3): 347-360, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33462377

RESUMO

DL-3-n-Butylphthalide (DL-NBP), a small molecular compound extracted from the seeds of Apium graveolens Linn (Chinese celery), has been shown to exert neuroprotective effects due to its anti-inflammatory, anti-oxidative and anti-apoptotic activities. DL-NBP not only protects against ischemic cerebral injury, but also ameliorates vascular cognitive impairment in dementia patients including AD and PD. In the current study, we investigated whether and how DL-NBP exerted a neuroprotective effect against diabetes-associated cognitive decline (DACD) in db/db mice, a model of type-2 diabetes. db/db mice were orally administered DL-NBP (20, 60, 120 mg· kg-1· d-1) for 8 weeks. Then the mice were subjected to behavioral test, their brain tissue was collected for morphological and biochemical analyses. We showed that oral administration of DL-NBP significantly ameliorated the cognitive decline with improved learning and memory function in Morris water maze testing. Furthermore, DL-NBP administration attenuated diabetes-induced morphological alterations and increased neuronal survival and restored the levels of synaptic protein PSD95, synaptophysin and synapsin-1 as well as dendritic density in the hippocampus, especially at a dose of 60 mg/kg. Moreover, we revealed that DL-NBP administration suppressed oxidative stress by upregulating Nrf2/HO-1 signaling, and increased brain-derived neurotrophic factor (BDNF) expression by activating PI3K/Akt/CREB signaling in the hippocampus. These beneficial effects of DL-NBP were observed in high glucose-treated PC12 cells. Our results suggest that DL-NBP may be a potential pharmacologic agent for the treatment of DACD.

5.
Nanotechnology ; 2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33461181

RESUMO

A novel hybrid method that combines the laser-focused atomic deposition (LFAD) and extremely ultraviolet (EUV) interference lithography has been introduced. The Cr grating manufactured by LFAD has advantages of excellent uniformity, low line edge roughness and its pitch value determined directly by nature constants (i.e. self-traceable). To further enhance the density of the Cr grating, the EUV interference lithography with 13.4 nm wavelength was employed, which replicated the master Cr grating onto a Si wafer with its pitch reduced to half. In order to verify the performance of the gratings manufactured by this novel method, both mask grating (Cr grating) and replicated grating (silicon grating) were calibrated by the metrological large-range scanning probe microscope (Met.LR-SPM) at PTB. The calibrated results show that both gratings have excellent short-term and long-term uniformity: (i) the calibrated position deviation (i.e. nonlinearity) of the grating is below ± 1 nm; (ii) the deviation of mean pitch values of 6 randomly selected measurement locations is below 0.003 nm. In addition, the mean pitch value of the Cr grating is calibrated as 212.781 ± 0.008 nm (k=2). It well agrees with its theoretical value of 212.7787 ± 0.0049 nm, confirming the self-traceability of the manufactured grating by the LFAD. The mean pitch value of the Si grating is calibrated as 106.460 ± 0.012 nm (k=2). It corresponds to the shrinking factor of 0.50033 of the applied EUV interference lithographic technique. This factor is very close to its theoretical value of 0.5. The uniform, self-traceable gratings fabricated using this novel approach can be well applied as reference materials in calibrating, e.g. the magnification and uniformity of almost all kinds of high-resolution microscopes for nanotechnology.

6.
Cell Death Dis ; 12(1): 107, 2021 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-33479232

RESUMO

Prolonged type 2 diabetes mellitus (T2DM) produces a common complication, peripheral neuropathy, which is accompanied by nerve fiber disorder, axon atrophy, and demyelination. Growing evidence has characterized the beneficial effects of acidic fibroblast growth factor (aFGF) and shown that it relieves hyperglycemia, increases insulin sensitivity, and ameliorates neuropathic impairment. However, there is scarce evidence on the role of aFGF on remodeling of aberrant myelin under hyperglycemia condition. Presently, we observed that the expression of aFGF was rapidly decreased in a db/db T2DM mouse model. Administration of exogenous aFGF was sufficient to block acute demyelination and nerve fiber disorganization. Furthermore, this strong anti-demyelinating effect was most likely dominated by an aFGF-mediated increase of Schwann cell (SC) proliferation and migration as well as suppression of its apoptosis. Mechanistically, the beneficial biological effects of aFGF on SC behavior and abnormal myelin morphology were likely due to the inhibition of hyperglycemia-induced oxidative stress activation, which was most likely activated by kelch-like ECH-associated protein 1 (Keap1)/nuclear factor erythroid-derived-like 2 (Nrf2) signaling. Thus, this evidence indicates that aFGF is a promising protective agent for relieving myelin pathology through countering oxidative stress signaling cascades under diabetic conditions.

7.
Immunobiology ; 226(1): 152033, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33321368

RESUMO

Spinal cord injury (SCI) is a leading cause of morbidity and disability in the world. Over the past few decades, the exact molecular mechanisms describing secondary, persistent injuries, as well as primary and transient injuries, have attracted massive attention to the clinicians and researchers. Recent investigations have distinctly shown the critical roles of innate and adaptive immune responses in regulating sterile neuroinflammation and functional outcomes after SCI. In past years, some promising advances in immunotherapeutic options have efficaciously been identified for the treatment of SCI. In our narrative review, we have mainly focused on the new therapeutic strategies such as the maturation and apoptosis of immune cells by several agents, mesenchymal stem cells (MSCs) as well as multi-factor combination therapy, which have recently provided novel ideas and prospects for the future treatment of SCI. This article also illustrates the latest progress in clarifying the potential roles of innate and adaptive immune responses in SCI, the progression and specification of prospective immunotherapy and outstanding issues in the area.

8.
Oxid Med Cell Longev ; 2020: 8586314, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33354279

RESUMO

There is a high incidence of acute and chronic skin defects caused by various reasons in clinically practice. The repair and functional reconstruction of skin defects have become a major clinical problem, which needs to be solved urgently. Previous studies have shown that fibroblast growth factor 10 (FGF10) plays a functional role in promoting the proliferation, migration, and differentiation of epithelial cells. However, little is known about the effect of FGF10 on the recovery process after skin damage. In this study, we found that the expression of endogenous FGF10 was increased during wound healing. We prepared FGF10-loaded poly(lactic-co-glycolic acid) (FGF10-PLGA) microspheres, and it could sustain release of FGF10 both in vitro and in vivo, accelerating wound healing. Further analysis revealed that compared with FGF10 alone, FGF10-PLGA microspheres significantly improved granulation formation, collagen synthesis, cell proliferation, and blood vessel density. In the meantime, we found that FGF10-PLGA microspheres inhibited the expression of endoplasmic reticulum (ER) stress markers. Notably, activating ER stress with tunicamycin (TM) reduced therapeutic effects of FGF10-PLGA microspheres in wound healing, whereas inhibition of ER stress with 4-phenyl butyric acid (4-PBA) improved the function of FGF10-PLGA microspheres. Taken together, this study indicates that FGF10-PLGA microspheres accelerate wound healing presumably through modulating ER stress.

9.
PeerJ ; 8: e10271, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33194431

RESUMO

Background: The mutualistic symbiosis between the gut microbial communities (microbiota) and their host animals has attracted much attention. Many factors potentially affect the gut microbiota, which also varies among host animals. The native Chinese three-keeled pond turtle (Chinemys reevesii) and the invasive red-eared slider turtle (Trachemys scripta elegans) are two common farm-raised species in China, with the latter generally considered a more successful species. However, supporting evidence from the gut microbiota has yet to be collected. Methods: We collected feces samples from these two turtle species raised in a farm under identical conditions, and analyzed the composition and relative abundance of the gut microbes using bacterial 16S rRNA sequencing on the Roach/454 platform. Results: The gut microbiota was mainly composed of Bacteroidetes and Firmicutes at the phylum level, and Porphyromonadaceae, Bacteroidaceae and Lachnospiraceae at the family level in both species. The relative abundance of the microbes and gene functions in the gut microbiota differed between the two species, whereas alpha or beta diversity did not. Microbes of the families Bacteroidaceae, Clostridiaceae and Lachnospiraceae were comparatively more abundant in C. reevesii, whereas those of the families Porphyromonadaceae and Fusobacteriaceae were comparatively more abundant in T. s. elegans. In both species the gut microbiota had functional roles in enhancing metabolism, genetic information processing and environmental information processing according to the Kyoto Encyclopedia of Genes and Genomes database. The potential to gain mass is greater in T. s. elegans than in C. reevesii, as revealed by the fact that the Firmicutes/Bacteroidetes ratio was lower in the former species. The percentage of human disease-related functional genes was lower in T. s. elegans than in C. reevesii, presumably suggesting an enhanced potential to colonize new habitats in the former species.

10.
3 Biotech ; 10(11): 496, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33150122

RESUMO

Herbaceous peony (Paeonia lactiflora Pall.) is a new high-end cut flower, but a large number of lateral branches often appear in some excellent cultivars, which is inconvenient for cut flower production. In the present study, we analyzed the effects of paclobutrazol (PBZ) on the lateral branches of P. lactiflora and adopted a next-generation sequencing approach to identify miRNAs and mRNAs that were differentially expressed involved in the PBZ response. Our results indicate that PBZ may inhibit the production of lateral branches on P. lactiflora. There were 827 differentially expressed genes (DEGs) and 104 differentially expressed miRNAs (DEMs). Integrative analysis revealed 29 miRNA-mRNA interactions related to PBZ stress. Our results provided a wealth of genetic information and data on metabolic pathways for revealing the regulatory mechanism of PBZ inhibition of the development of lateral branches in P. lactiflora and provided a new possibility for reducing lateral branch formation in the production of herbaceous peony cut flowers.

11.
Nat Commun ; 11(1): 5513, 2020 11 02.
Artigo em Inglês | MEDLINE | ID: mdl-33139730

RESUMO

Cyclin D1 is one of the most important oncoproteins that drives cancer cell proliferation and associates with tamoxifen resistance in breast cancer. Here, we identify a lncRNA, DILA1, which interacts with Cyclin D1 and is overexpressed in tamoxifen-resistant breast cancer cells. Mechanistically, DILA1 inhibits the phosphorylation of Cyclin D1 at Thr286 by directly interacting with Thr286 and blocking its subsequent degradation, leading to overexpressed Cyclin D1 protein in breast cancer. Knocking down DILA1 decreases Cyclin D1 protein expression, inhibits cancer cell growth and restores tamoxifen sensitivity both in vitro and in vivo. High expression of DILA1 is associated with overexpressed Cyclin D1 protein and poor prognosis in breast cancer patients who received tamoxifen treatment. This study shows the previously unappreciated importance of post-translational dysregulation of Cyclin D1 contributing to tamoxifen resistance in breast cancer. Moreover, it reveals the novel mechanism of DILA1 in regulating Cyclin D1 protein stability and suggests DILA1 is a specific therapeutic target to downregulate Cyclin D1 protein and reverse tamoxifen resistance in treating breast cancer.


Assuntos
Antineoplásicos Hormonais/farmacologia , Neoplasias da Mama/tratamento farmacológico , Ciclina D1/genética , RNA Longo não Codificante/metabolismo , Tamoxifeno/farmacologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antineoplásicos Hormonais/uso terapêutico , Neoplasias da Mama/genética , Neoplasias da Mama/metabolismo , Neoplasias da Mama/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , Intervalo Livre de Doença , Resistencia a Medicamentos Antineoplásicos/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Técnicas de Silenciamento de Genes , Humanos , Pessoa de Meia-Idade , Prognóstico , Processamento de Proteína Pós-Traducional/genética , Estabilidade Proteica , Proteólise , RNA Longo não Codificante/genética , Tamoxifeno/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
12.
Am J Alzheimers Dis Other Demen ; 35: 1533317520962660, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33089704

RESUMO

AIM: There are currently no established, clinically relevant, non-invasive markers of cognitive impairment, except for age and APOE genotype. METHODS: A cross-sectional study of 1,296 participants from Nanchang, China, has been conducted. We collected data from Mini-Mental State Examination (MMSE) scores, internal lipid profiles and body lipid profiles, age and other factors that may have an effect on cognitive impairment. RESULTS: Internal lipid profiles (OR = 1.03 [95%CI, 1.00-1.06], P = 0.024), body lipid profiles (OR = 1.05 [95%CI, 1.01-1.09], P = 0.014), and age (OR = 1.03 [95%CI, 1.01-1.05], P < 0.001) were all positively correlated with cognitive impairment. CONCLUSIONS: Cognitive impairment was more frequent in female patients with high internal lipid profiles or body lipid profiles, and these characteristics were related to age and education.

13.
Zookeys ; 974: 131-159, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33110381

RESUMO

A new species of the genus Megophrys is described from Guizhou Province, China. Molecular phylogenetic analyses supported the new species as an independent clade nested into the Megophrys. The new species could be distinguished from its congeners by a combination of the following characters: body size moderate (SVL 49.3-58.2 mm in males); vomerine ridges present distinctly, vomerine teeth present; tongue feebly notched behind; tympanum distinctly visible, oval; two metacarpal tubercles in hand; toes with one-third webbing and wide lateral fringes; heels overlapped when thighs are positioned at right angles to the body; tibiotarsal articulation reaching the level between tympanum and eye when leg stretched forward; an internal single subgular vocal sac present in male; in breeding male, the nuptial pads with large and sparse black nuptial spines present on the dorsal bases of the first two fingers.

14.
Artigo em Inglês | MEDLINE | ID: mdl-33037726

RESUMO

Nifekalant has been used in the treatment of atrial arrhythmia recently. However, there is no consensus on the preferable nifekalant dose to treat atrial fibrillation (AF). The purpose of this study was to explore efficacy and safety of different doses of nifekalant in the cardioversion of persistent AF. The study was a single-centre, randomized controlled trial. All subjects received nifekalant or placebo intravenously, and the nifekalant was given at the dosage of 0.3, 0.4 or 0.5 mg/kg. Primary efficacy end-point: compared with 0.3 mg group, the rate of cardioversion to sinus rhythm from AF in 0.4 and 0.5 mg group was higher. The 0.4 and 0.5 mg/kg doses were associated with a similar magnitude of efficacy (P > .05). Secondary efficacy end-point: termination rates of AF in the group of 0.4 mg and 0.5 mg were higher than 0.3 mg. Primary safety end-point: the rate of Torsades de Pointes or ventricular fibrillation was numerically lower in the 0.4 mg group than 0.5 mg group (P = .02). Secondary safety end-point: The rates of the majority of other common drug-related adverse events in the group of 0.5 and 0.4 mg were higher than the 0.3 mg group. A 0.4 mg/kg dose of intravenous nifekalant may be recommended during the radiofrequency ablation for persistent AF considering the benefit-risk profile.

15.
Medicine (Baltimore) ; 99(40): e22572, 2020 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-33019469

RESUMO

RATIONALE: Atorvastatin is the most common drug used in therapy for cardiovascular diseases. The most common adverse side effects associated with statins are myopathy and hypertransaminasemia. Here, we report a rare case of gamma glutamyl transpeptidase (GGT) elevation induced by atorvastatin. PATIENT CONCERNS: A 47-year-old male was admitted to our hospital with dyslipidemia, he had been taking pitavastatin 2 mg/day for 2 months. The levels of total cholesterol (265.28 mg/dL) and low-density lipoprotein-cholesterol (LDL) (179.15 mg/dL) were also high. DIAGNOSIS: Blood lipid test showed mixed dyslipidemia. INTERVENTION: Atorvastatin 10 mg/day was given to the patient. OUTCOMES: The patient came back to our hospital for blood tests after 4 weeks. Although no symptoms were detectable, the patient's GGT level was markedly elevated (up to 6-fold over normal level) with less marked increases in alkaline phosphatase (ALP) and alanine aminotransferase (ALT). The serum GGT level returned to normal within 6 weeks of cessation of atorvastatin. LESSONS: This is a case of GGT elevation without hyperbilirubinemia, hypertransaminasemiam, or serum creatine phosphokinase (CPK) abnormalities despite an atorvastatin regimen. This case highlights GGT elevation caused by atorvastatin, a rare but serious condition. Clinicians should be aware of these possible adverse effects and monitor liver function tests in patients on statin therapy.


Assuntos
Atorvastatina/efeitos adversos , Dislipidemias/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/efeitos adversos , Quinolinas/efeitos adversos , gama-Glutamiltransferase/efeitos dos fármacos , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Atorvastatina/administração & dosagem , Atorvastatina/uso terapêutico , Doenças Cardiovasculares/tratamento farmacológico , HDL-Colesterol/sangue , LDL-Colesterol/sangue , Dislipidemias/diagnóstico , Humanos , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Quinolinas/administração & dosagem , Quinolinas/uso terapêutico , Suspensão de Tratamento , gama-Glutamiltransferase/sangue
16.
ESC Heart Fail ; 2020 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-32977362

RESUMO

AIMS: Sacubitril-valsartan has been shown to have superior effects over angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in patients with heart failure (HF) and hypertension. The efficacy and safety of sacubitril-valsartan in patients with HF are controversial. We performed a meta-analysis of randomized controlled trials to assess and compare the effect and adverse events of sacubitril-valsartan, valsartan, and enalapril in patients with HF. METHODS AND RESULTS: We conducted a systematic search using PubMed, Embase, the Cochrane Library, and ClinicalTrials.gov. Randomized controlled trials involving the use of sacubitril-valsartan in patients with HF were included. We assessed the pooled odds ratio (OR) of all-cause mortality, cardiovascular mortality, and hospitalization for HF in fixed-effects models and the pooled risk ratio (RR) of symptomatic hypotension, worsening renal function, and hyperkalaemia in fixed-effects models. Of the 315 identified records, six studies involving 14 959 patients were eligible for inclusion. Sacubitril-valsartan reduced the endpoints of all-cause mortality and cardiovascular mortality in patients with HF with reduced ejection fraction (HFrEF) in three trials with pooled ORs of 0.83 (P = 0.0006) and 0.78 (P < 0.0001), respectively. Regarding the composite outcome of hospitalization for HF in five trials, the pooled OR was 0.79 (P < 0.00001). Compared with enalapril or valsartan, sacubitril-valsartan was associated with a high risk of symptomatic hypotension (RR 1.47, P < 0.00001), low risk of worsening renal function (RR 0.81, P = 0.005), and low rate of serious hyperkalaemia (≥6.0 mmol/L) (RR 0.76, P = 0.0007) in all six trials. CONCLUSIONS: Compared with angiotensin-converting enzyme inhibitors or angiotensin receptor blockers, sacubitril-valsartan significantly decreased the risk of death from all causes or cardiovascular causes in HFrEF and hospitalization for HF in both patients with HFrEF and HF with preserved ejection fraction. Sacubitril-valsartan reduced the risk of renal dysfunction and serious hyperkalaemia but was associated with more symptomatic hypotension.

17.
Am J Transl Res ; 12(7): 3822-3841, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32774738

RESUMO

Inositol-1,4,5-triphosphate-receptor 1 (IP3R1), a Ca2+ channel in the sarcoplasmic reticulum membrane, is an effective regulator of Ca2+ release involved in the pathology of most cardiovascular diseases. Our study aim to investigate the underlying mechanism by which IP3R1 signaling mediates the process of homocysteine (Hcy)-induced Ca2+ accumulation via interaction with sodium current (Nav1.5) in atrium. We utilized whole-cell patch-clamp analysis and flow cytometry to detect the abnormal electrical activity in mouse atrial myocytes (MACs) obtained from C57B6 mice fed with high-Hcy diet. The results represented not only an increase in protein levels of Nav1.5 and IP3R1, but also an enhanced intracellular levels of Ca2+, and prolonged action potential duration (APD). However, the inhibition of IP3R1 or Nav1.5 gene could both attenuate Ca2+ accumulation in MACs triggered by Hcy, as well as abnormal electrical activity. In addition, Hcy increased the interaction between IP3R1 and Nav1.5. These data suggest that Hcy induced Ca2+ accumulation is mediated by the IP3R1/Nav1.5 signaling pathway, accompanied with the influx of Na+ and Ca2+, which act as triggers for electrical remodeling.

18.
Reprod Biol Endocrinol ; 18(1): 83, 2020 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-32787870

RESUMO

BACKGROUND: Through this prospective study, we aimed to explore the change of molecular modification after the transient scrotal hyperthermia on human sperm. METHODS: Ten healthy subjects selected with strict screening criteria underwent testicular warming in a 43 °C water bath for 30 min a day for 10 consecutive days. Semen samples were collected 2 weeks before the first heat treatment and 6 weeks after the first heat treatment. Proteins from the samples were labeled with isobaric tags for relative and absolute quantitation and analyzed by two-dimensional liquid chromatography-tandem mass spectrometry. RESULTS: In contrast to the control, of the 3446 proteins identified, 61 proteins were deregulated: 28 were up-regulated and 33 were down-regulated. Approximately 95% of the differentially expressed proteins were found to participate in spermatogenesis, fertilization, or other aspects of reproduction. In particular, the expression of sperm motility and energy metabolism-related proteins AKAP4, SPESP1, ODF1, ODF2, GAPDHS, and ACTRT2, validated by western blotting of the proteins obtained from human and mouse samples, tended to be reduced under scrotal hyperthermia. CONCLUSIONS: The results indicated that the proteins AKAP4, ODF1, ODF2, GAPDHS, SPESP1, and ACTRT2, play an important role in the heat-induced reversible reduction in sperm concentration and motility and have the potential to be the biomarkers and clinical targets for scrotal heat treatment induced male infertility.

19.
Front Cell Dev Biol ; 8: 602, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32766246

RESUMO

Diabetes significantly induces cognitive dysfunction. Neuronal apoptosis is the main cause of diabetes-induced cognitive decline (DICD). Apoptosis signal-regulating kinase 1 (ASK1) and endoplasmic reticulum (ER) stress are remarkably activated by diabetes. The role and relationship of ASK1-JNK1/2 signaling and ER stress in DICD have not yet been elucidated. In this study, we used db/db mice as the DICD animal model and confirmed that db/db mice displayed cognitive decline with inferior learning and memory function. Diabetes significantly induced morphological and structural changes, excessive neuronal apoptosis, Aß1 - 42 large deposition, and synaptic dysfunction in the hippocampus. Mechanistic studies found that diabetes significantly triggered ASK1-JNK1/2 signaling activation and increased ER stress in the hippocampus. Moreover, diabetes enhanced the formation of the IRE1α-TRAF2-ASK1 complex, which promotes the crosstalk of ER stress and the ASK1-JNK1/2 pathway during DICD. Furthermore, 4-PBA treatment blocked high glucose (HG)-induced ASK1-JNK1/2 signaling activation, and excessive apoptosis in vitro. Inhibiting ASK1 via siRNA remarkably ameliorated the HG-induced increase in p-IRE1α and associated apoptosis in SH-SY5Y cells, suggesting that ASK1 is essential for the assembly and function of the proapoptotic kinase activity of the IRE1α signalosome. In summary, ER stress and ASK1-JNK1/2 signaling play causal roles in DICD development, which has crosstalk through the formation of the IRE1α-TRAF2-ASK1 complex.

20.
Nanoscale ; 12(30): 16348-16358, 2020 Aug 06.
Artigo em Inglês | MEDLINE | ID: mdl-32725043

RESUMO

Neuromorphic computing systems have shown powerful capability in tasks, such as recognition, learning, classification and decision-making, which are both challenging and inefficient in using the traditional computation architecture. The key elements including synapses and neurons, and their feasible hardware implementation are essential for practical neuromorphic computing. However, most existing synaptic devices used to emulate functions of a single synapse and the synapse-based networks are more energy intensive and less sustainable than their biological counterparts. The dendritic functions such as integration of spatiotemporal signals and spike-frequency coding characteristics have not been well implemented in a single synaptic device and thus play an imperative role in future practical hardware-based spiking neural networks. Moreover, most emerging synaptic transistors are fabricated by nanofabrication processes without CMOS compatibility for further wafer-scale integration. Herein, we demonstrate a novel ionic-gated silicon nanowire synaptic field-effect transistor (IGNWFET) with low power consumption (<400 fJ per switching event) based on the standard CMOS process platform. For the first time, the dendritic integration and dual-synaptic dendritic computations (such as "Add" and "Subtraction") could be realized by processing frequency coded spikes using a single device. Meanwhile, multi-functional characteristics of artificial synapses including the short-term and long-term synaptic plasticity, paired pulse facilitation and high-pass filtering were also successfully demonstrated based on 40 nm wide IGNWFETs. The migration of ions in polymer electrolyte and trapping in high-k dielectric were also experimentally studied in-depth to understand the short-term plasticity and long-term plasticity. Combined with statistical uniformity across a 4-inch wafer, the comprehensive performance of IGNWFET demonstrates its potential application in future biologically emulated neuromorphic systems.

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