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1.
EMBO Rep ; : e52124, 2021 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-34647680

RESUMO

This study explores the role of the long noncoding RNA (LncRNA) CRNDE in cisplatin (CDDP) resistance of gastric cancer (GC) cells. Here, we show that LncRNA CRNDE is upregulated in carcinoma tissues and tumor-associated macrophages (TAMs) of GC patients. In vitro experiments show that CRNDE is enriched in M2-polarized macrophage-derived exosomes (M2-exo) and is transferred from M2 macrophages to GC cells via exosomes. Silencing CRNDE in M2-exo reverses the promotional effect of M2-exo on cell proliferation in CDDP-treated GC cells and homograft tumor growth in CDDP-treated nude mice. Mechanistically, CRNDE facilitates neural precursor cell expressed developmentally downregulated protein 4-1 (NEDD4-1)-mediated phosphatase and tensin homolog (PTEN) ubiquitination. Silencing CRNDE in M2-exo enhances the CDDP sensitivity of GC cells treated with M2-exo, which is reduced by PTEN knockdown. Collectively, these data reveal a vital role for CRNDE in CDDP resistance of GC cells and suggest that the upregulation of CRNDE in GC cells may be attributed to the transfer of TAM-derived exosomes.

2.
Rev Sci Instrum ; 92(9): 094703, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34598530

RESUMO

In circular waveguides, the TE01 mode has the lowest transmission loss, which is very suitable for long-distance transmission of high-power microwaves (HPMs). The output mode of HPM sources is mainly the TM01 mode; however, there are few research studies on mode converters of TM01-TE01. In this paper, a high efficiency HPM TM01-TE01 mode converter is designed; compared with the traditional TM01-TE01 mode converters, the structure of the mode converter is compact and easier to process. It is mainly composed of an input circular waveguide, a tapered rectangular waveguide, a 90° bent rectangular waveguide, and an output circular waveguide. A prototype with a center frequency of 2.4 GHz is fabricated and HPM experiments are carried out. The transmission efficiency of this device reaches 99.8% in the simulation, and the measured transmission efficiency is more than 98%. Additionally, the measured power handling capacity is more than 1 GW, which is consistent with simulation. This design has important reference significance for the design of long-distance power transmission devices and HPM mode converters.

3.
J Cell Mol Med ; 2021 Oct 02.
Artigo em Inglês | MEDLINE | ID: mdl-34599867

RESUMO

MALAT1, which is disorderly expressed in the growth, invasion, migration and cancer cell apoptosis, was shown to be associated with normal-tension glaucoma (NTG), a type of optic neuropathy. The haplotype in MALAT1 affects its expression and is correlated with human diseases like normal-tension glaucoma (NTG). However, the underlying detailed mechanism remains unclear. In this study, we aimed to analyse the association between MALAT1 haplotype and the severity of NTG in a molecular level. Quantitative real-time PCR, ELISA and luciferase assays were performed to establish the underlying signalling pathways. RNFL thickness, RA and C/D ratio were calculated for NTG patients. Accordingly, GGGT haplotype was demonstrated to be associated with a decreased risk of NTG. The MALAT1 level in serum of NTG patients carrying GGGT haplotype was significantly decreased compared with NTG patients carrying other haplotypes, along with elevated miR-1 expression and diminished IL-6 expression. NTG patients carrying GGGT haplotype had thicker RNFL and RA, but a smaller C/D ratio. Sequence analysis found potential target sites of miR-1 on MALAT1 and IL-6, and luciferase assay confirmed the inhibitory effect of miR-1 on MALAT1 and IL-6 expression. Meanwhile, MALAT1 also down-regulated miR-1 expression and consequently up-regulated IL-6 expression. This study presented evidence for a regulatory network containing MALAT1, miR-1 and IL-6, and further demonstrated the effect of MALAT1 haplotype on the risk and severity of NTG.

4.
Artigo em Inglês | MEDLINE | ID: mdl-34618677

RESUMO

This article investigates the stabilization of stochastic highly non-linear coupled systems (SHNCSs) with multiple time delays by using periodically intermittent control (PIC). It is worth noting that coefficients in SHNCSs dissatisfy the linear growth condition, which weakens the previous stability conditions. In addition, PIC and multiple time delays are first introduced into the study of highly nonlinear systems, which leads to the existing methods being inapplicable to investigate the stability of SHNCSs with multiple time delays. Therefore, a novel Halanay-type differential inequality is established, which can be employed to deal with highly nonlinear systems with PIC. Based on the Lyapunov method, the graph theory, and the novel differential inequality, SHNCSs with multiple time delays are first studied, and stability criteria are presented. Next, the theoretical results can be applied to modified FitzHugh-Nagumo models. At last, a numerical example is presented to show the effectiveness of our results.

5.
BMC Genomics ; 22(1): 731, 2021 Oct 08.
Artigo em Inglês | MEDLINE | ID: mdl-34625025

RESUMO

BACKGROUND: Trees such as Populus are planted extensively for reforestation and afforestation. However, their successful establishment greatly depends upon ambient environmental conditions and their relative resistance to abiotic and biotic stresses. Polyphenol oxidase (PPO) is a ubiquitous metalloproteinase in plants, which plays crucial roles in mediating plant resistance against biotic and abiotic stresses. Although the whole genome sequence of Populus trichocarpa has long been published, little is known about the PPO genes in Populus, especially those related to drought stress, mechanical damage, and insect feeding. Additionally, there is a paucity of information regarding hormonal responses at the whole genome level. RESULTS: A genome-wide analysis of the poplar PPO family was performed in the present study, and 18 PtrPPO genes were identified. Bioinformatics and qRT-PCR were then used to analyze the gene structure, phylogeny, chromosomal localization, gene replication, cis-elements, and expression patterns of PtrPPOs. Sequence analysis revealed that two-thirds of the PtrPPO genes lacked intronic sequences. Phylogenetic analysis showed that all PPO genes were categorized into 11 groups, and woody plants harbored many PPO genes. Eighteen PtrPPO genes were disproportionally localized on 19 chromosomes, and 3 pairs of segmented replication genes and 4 tandem repeat genomes were detected in poplars. Cis-acting element analysis identified numerous growth and developmental elements, secondary metabolism processes, and stress-related elements in the promoters of different PPO members. Furthermore, PtrPPO genes were expressed preferentially in the tissues and fruits of young plants. In addition, the expression of some PtrPPOs could be significantly induced by polyethylene glycol, abscisic acid, and methyl jasmonate, thereby revealing their potential role in regulating the stress response. Currently, we identified potential upstream TFs of PtrPPOs using bioinformatics. CONCLUSIONS: Comprehensive analysis is helpful for selecting candidate PPO genes for follow-up studies on biological function, and progress in understanding the molecular genetic basis of stress resistance in forest trees might lead to the development of genetic resources.


Assuntos
Catecol Oxidase , Proteínas de Plantas/genética , Populus , Catecol Oxidase/genética , Secas , Regulação da Expressão Gênica de Plantas , Filogenia , Populus/enzimologia , Populus/genética , Estresse Fisiológico
6.
PLoS One ; 16(9): e0257248, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34507348

RESUMO

Meiosis is a complex process involving the expression and interaction of numerous genes in a series of highly orchestrated molecular events. Fam9b localized in Xp22.3 has been found to be expressed in testes. However, FAM9B expression, localization, and its role in meiosis have not been previously reported. In this study, FAM9B expression was evaluated in the human testes and ovaries by RT-PCR, qPCR, and western blotting. FAM9B was found in the nuclei of primary spermatocytes in testes and specifically localized in the synaptonemal complex (SC) region of spermatocytes. FAM9B was also evident in the follicle cell nuclei and diffusely dispersed in the granular cell cytoplasm. FAM9B was partly co-localized with SYCP3, which is essential for both formation and maintenance of lateral SC elements. In addition, FAM9B had a similar distribution pattern and co-localization as γH2AX, which is a novel biomarker for DNA double-strand breaks during meiosis. All results indicate that FAM9B is a novel meiosis-associated protein that is co-localized with SYCP3 and γH2AX and may play an important role in SC formation and DNA recombination during meiosis. These findings offer a new perspective for understanding the molecular mechanisms involved in meiosis of human gametogenesis.

7.
Front Cell Infect Microbiol ; 11: 706252, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34513728

RESUMO

The pandemic of COVID-19 by SARS-CoV-2 has become a global disaster. However, we still don't know how specific SARS-CoV-2-encoded proteins contribute to viral pathogenicity. We found that SARS-CoV-2-encoded membrane glycoprotein M could induce caspase-dependent apoptosis via interacting with PDK1 and inhibiting the activation of PDK1-PKB/Akt signaling. Our investigation further revealed that SARS-CoV-2-encoded nucleocapsid protein N could specifically enhance the M-induced apoptosis via interacting with both M and PDK1, therefore strengthening M-mediated attenuation of PDK1-PKB/Akt interaction. Furthermore, when the M-N interaction was disrupted via certain rationally designed peptides, the PDK1-PKB/Akt signaling was restored, and the boosting activity of N on the M-triggered apoptosis was abolished. Overall, our findings uncovered a novel mechanism by which SARS-CoV-2-encoded M triggers apoptosis with the assistance of N, which expands our understanding of the two key proteins of SARS-CoV-2 and sheds light on the pathogenicity of this life-threatening virus.


Assuntos
COVID-19 , SARS-CoV-2 , Apoptose , Humanos , Glicoproteínas de Membrana , Proteínas do Nucleocapsídeo , Glicoproteína da Espícula de Coronavírus
8.
Pest Manag Sci ; 2021 Aug 31.
Artigo em Inglês | MEDLINE | ID: mdl-34467614

RESUMO

BACKGROUND: Potato late blight (PLB) caused by Phytophthora infestans is one of the most devastating plant diseases. The heavy use of chemical control agents is at odds with the development of sustainable and environmentally friendly agriculture practices. It is necessary to screen the antagonistic microorganisms of P. infestans and provide a new choice of PLB biocontrol. RESULTS: In vitro, eight bacterial strains (A, B, C, D, E, F, G, H) isolated from the rhizosphere of resistant potato plants had a significant inhibitory effect on the mycelium growth of P. infestans, and the inhibition rate was 35.02-79.20%. These isolates were assigned to Streptomyces, Pseudomonas, Saccharothrix and Nocardiopsis by phylogenetic analysis of 16S rRNA genes. Their physiological and biochemical characteristics suggested that they can produce cellulase and catalase, which may help to inhibit the infection of P. infestans. In vivo, each strain significantly inhibited the infection of P. infestans after individual inoculation into potato tubers, and no strains posed a pathogenic threat to tubers. In the field environment, multibacterial treatment significantly reduced the disease index. Compared with the control, multibacterial and single H treatment significantly increased the microbial species and abundance of the potato rhizosphere and enriched potential beneficial bacteria such as Rhizobiaceae. Meanwhile, multi-bacterial and single H treatment significantly reduced the abundance of Enterobacteriaceae and Bacillaceae. CONCLUSION: Our results provide some valuable native strains from the potato rhizosphere with the ability to inhibit P. infestans in vivo and in vitro, which may be a new option for PLB biocontrol.

9.
Biomed Mater ; 16(6)2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34571498

RESUMO

Oral insulin has been regarded as the best alternative to insulin injection in therapy of diabetes because of its convenience and painlessness. However, several obstacles in the gastrointestinal tract, such as gastric acid and enzyme, greatly reduce the bioavailability of oral insulin. Herein, we report design and preparation of poly (d, l-lactic-co-glycolic acid) nanoparticles (PLGA NPs) coated with 5ß-cholanic acid modified glycol chitosan (GC-CA) (GC-CA@PLGA NPs) to improve the oral delivery of insulin. The GC-CA@PLGA NPs with the size of (302.73 ± 5.13 nm) and zeta potential of (25.03 ± 0.31 mV) were synthesized using the double-emulsion method. The insulin-loading capacity and encapsulation efficiency were determined to be 5.77 ± 0.58% and 51.99 ± 5.27%, respectively. Compared with GC-modified PLGA NPs (GC@PLGA NPs) and bare PLGA NPs, the GC-CA@PLGA NPs showed excellent stability and uptake by Caco-2 cells after simulated gastric acid digestion. Further experiment suggests good biocompatibility of GC-CA@PLGA NPs, including hemolysis and cytotoxicity. Inin vivoexperiment, the insulin loaded in the GC-CA@PLGA NPs exhibited a long-term and stable release profile for lowering blood glucose and presented 30.43% bioavailability in oral administration. In brief, we have developed an efficient and safe drug delivery system, GC-CA@PLGA NPs, for significantly improved oral administration of insulin, which may find potential application in the treatment of diabetes.

10.
J Hazard Mater ; 423(Pt B): 127150, 2021 Sep 09.
Artigo em Inglês | MEDLINE | ID: mdl-34530277

RESUMO

The rapid spread of antibiotic resistance genes (ARGs) has posed a risk to human health. Here, the effects of biochar (BC) on the horizontal transfer of ARG-carrying plasmids to Escherichia coli via transformation were systematically investigated. BC could significantly inhibit the transformation of ARGs and the inhibition degree increased with pyrolysis temperature. Rice straw-derived BC showed a stronger inhibitory effect on the transformation of ARGs than that of peanut shell-derived BC from the same pyrolysis temperature. The inhibitory effect of BC from low pyrolysis temperature (300 â„ƒ) was mainly caused by BC dissolutions, while it was mainly attributed to BC solids for high pyrolysis temperature (700 â„ƒ) BC. BC dissolutions could induce intramolecular condensation and even agglomeration of plasmids, hindering their transformation into competent bacteria. The cell membrane permeability was slightly decreased in BC dissolutions, which might also contribute to the inhibitory effect. Plasmid can be adsorbed by BC solids and the adsorption increased with BC pyrolysis temperature. Meanwhile, BC-adsorbed plasmid could hardly be transformed into E. coli. BC solids could also deactivate E. coli and thereby inhibit their uptake of ARGs. These findings provide a way using BC to limit the spread of ARGs in the environment.

11.
J Hazard Mater ; 423(Pt B): 127056, 2021 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-34547692

RESUMO

Reducing the cost of pellet additives as a substitute for reducing bentonite binder is an important research direction of new pellet additives. There are some industrial solid wastes that have the similar physical and chemical properties to bentonite, and SiO2 content of them may be much lower than bentonite, but also contains a lot of Fe2O3, Al2O3, MgO, B2O3 and other components beneficial to the quality of pellets, which have been paid more attention by many pellet workers. In this review, the effect mechanism of Fe2O3, Na2O/K2O, Al2O3, SiO2, CaO, MgO and B2O3 in the industrial solid wastes on the fired strength and reduction expansion of pellets were systematically summarized. At the same time, the influences of five representative large scale modified industrial solid waste additives including iron tailings, bauxite tailings, fly ash, red mud and boron sludge on the properties of green pellets and finished pellets were described in detail. It can be seen that the applications of industrial solid waste in pellet additives can partially or completely replace bentonite binder, especially fly ash, red mud and boron sludge, which can not only improve the quality of pellets, but also decrease the cost, save energy and reduce pollution, with significant economic benefits.

12.
Plant Sci ; 311: 110996, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34482908

RESUMO

Rubus chingii, is widely distributed in many Asian countries and well known for its medicinal and dietary properties. Diversity of fruit color in raspberry has been attributed to the presence of either anthocyanins or carotenoids. In this study, we investigated anthocyanins and carotenoids, and their biosynthesis by LC-MS/MS. Six anthocyanins mainly consisted of flavanol-anthocyanins while five carotenoids mainly consisted of ß-citraurin esters. Flavanol-anthocyanins were produced from an offshoot of the anthocyanin biosynthesis, which started with biosynthesis of flavanols and anthocyanidin by leucoanthocyanidin reductase (LAR)/anthocyanidin reductase (ANR) and anthocyanidin synthase (ANS/LDOX) respectively. ß-citraurin esters were produced from cleavage of zeaxanthin and esterification by organic acid, which was an offshoot of the carotenoid biosynthesis. The offshoot started with biosynthesis of zeaxanthin and ß-citraurin by carotene ß-hydroxylase (CHYB/LUT5) and carotenoid cleavage dioxygenase (CCD) respectively. During fruit ripening, biosynthesis of flavanols and anthocyanins was down-regulated by genes/proteins involved in phenylpropanoid and flavonoid biosynthesis, while biosynthesis of ß-citraurin esters was up-regulated by imbalanced expression of genes/proteins involved in ß,ß-ring and ß, ε-ring hydroxylation. Thus, ß-citraurin esters, instead of anthocyanins imparted reddish color to the ripe fruit. These pigments and their biosynthesis in R. chingii are totally different from what occurs in other raspberry species.


Assuntos
Antocianinas/metabolismo , Carotenoides/metabolismo , Frutas/crescimento & desenvolvimento , Frutas/metabolismo , Pigmentação/fisiologia , Rubus/crescimento & desenvolvimento , Rubus/metabolismo , Antocianinas/genética , China , Frutas/anatomia & histologia , Regulação da Expressão Gênica de Plantas , Genes de Plantas , Pigmentação/genética , Rubus/anatomia & histologia
13.
ACS Chem Neurosci ; 12(19): 3719-3732, 2021 Oct 06.
Artigo em Inglês | MEDLINE | ID: mdl-34519476

RESUMO

Protein citrullination (deimination of arginine residue) is a well-known biomarker of inflammation. Elevated protein citrullination has been shown to colocalize with extracellular amyloid plaques in postmortem AD patient brains. Amyloid-ß (Aß) peptides which aggregate and accumulate in the plaques of Alzheimer's disease (AD) have sequential N-terminal truncations and multiple post-translational modifications (PTM) such as isomerization, pyroglutamate formation, phosphorylation, nitration, and dityrosine cross-linking. However, no conclusive biochemical evidence exists whether citrullinated Aß is present in AD brains. In this study, using high-resolution mass spectrometry, we have identified citrullination of Aß in sporadic and familial AD brains by characterizing the tandem mass spectra of endogenous N-truncated citrullinated Aß peptides. Our quantitative estimations demonstrate that ∼ 35% of pyroglutamate3-Aß pool was citrullinated in plaques in the sporadic AD temporal cortex and ∼ 22% in the detergent-insoluble frontal cortex fractions. Similarly, hypercitrullinated pyroglutamate3-Aß (∼ 30%) was observed in both the detergent-soluble as well as insoluble Aß pool in familial AD cases. Our results indicate that a common mechanism for citrullination of Aß exists in both the sporadic and familial AD. We establish that citrullination of Aß is a remarkably common PTM, closely associated with pyroglutamate3-Aß formation and its accumulation in AD. This may have implications for Aß toxicity, autoantigenicity of Aß, and may be relevant for the design of diagnostic assays and therapeutic targeting.

14.
Aquat Toxicol ; 239: 105956, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34496328

RESUMO

Intensive aquaculture often results in immunosuppression in fish, which may cause a series of diseases. In this study, to investigate the immunosuppressive mechanisms in fish, tilapia were intrapleural injected cyclophosphamide (CTX) at the doses of 10, 25, 50, 75 and 100 mg·kg-1 to induce immunosuppression. We determined the viability of immune cells, the content of lysozyme (LZM) and immunoglobulin M (IgM), the levels of nitric oxide (NO) and antioxidant parameters. Meanwhile, the mRNA levels of complement C3 (c3), igm and the genes associated with the TLR-NF-κB signaling pathway in the head kidney (HK) and spleen were also determined. The results showed that CTX had a significant cytotoxic effect on peripheral blood leukocytes, HK macrophages and spleen cells in a dose-dependent manner. The protein and mRNA levels of C3 and IgM were down-regulated with the increase of CTX concentrations in serum, HK and/or spleen. The NO and LZM contents decreased significantly in HK and spleen after CTX treatments with 75 and 100 mg·kg-1. CTX treatments with 50, 75 and/or 100 mg·kg-1 markedly decreased the antioxidant ability and enhanced lipid peroxidation in HK and spleen. Furthermore, qPCR data showed that CTX treatments with 50-100 mg·kg-1 clearly down-regulated the mRNA levels of tlr2, myd88, irak1, traf6, nfκb1, nfκb2, il-6, il-10 and tnf-α in the HK and/or spleen. Overall results suggested that CTX treatment had a cytotoxic effect on immune cells, induced lipid peroxidation, decreased the antioxidant capacity and inhibited immune function. The immunosuppressive mechanisms of CTX may be associated with the TLR-NF-κB signaling pathway.


Assuntos
Ciclídeos , Doenças dos Peixes , Poluentes Químicos da Água , Animais , Antioxidantes , Ciclídeos/metabolismo , Ciclofosfamida/toxicidade , Imunidade , NF-kappa B/genética , NF-kappa B/metabolismo , Transdução de Sinais , Poluentes Químicos da Água/toxicidade
15.
Photodiagnosis Photodyn Ther ; 36: 102544, 2021 Sep 20.
Artigo em Inglês | MEDLINE | ID: mdl-34551324

RESUMO

BACKGROUND: Dissecting cellulitis of the scalp (DCS) is a rare but distinctive, chronic suppurative condition, and the treatment is a therapeutic challenge. Recently, treatment of DCS with 5-aminolaevulinic acid photodynamic therapy (ALA-PDT) has been considered as a potential option. OBJECTIVE: To evaluate the efficacy and safety of 20% ALA-PDT pretreated by fire needle in the treatment of DCS. MATERIALS AND METHODS: Topical 20% ALA-PDT with fire needle intervention as a pretreatment, was applied to six patients with DCS. All patients completed three sessions treatment at an interval of ten days. They were assessed for the efficacy at the baseline and on ten days after each treatment. According to the reduction of lesions and the improvements of patients' symptoms after each session, the objective assessment of therapeutic effect was divided into four grades. The adverse effects were recorded. RESULTS: A total of six male patients were enrolled in our study. After three sessions of ALA-PDT, among them, three patients recovered, two patients achieved significant improvement and one patient achieved partial response.Patient 4 (Pt.4) relapsed at 6-month follow-up. Pt.1 and Pt.6. maintained complete response after one year follow-up. We also found that the clearance rate of the popular/nodular and cyst/abscess was much higher than sinus. CONCLUSION: 20% ALA-PDT pretreated by fire needle could be an effective, minimally-invasive, safe method for DCS patients. Lesion in the early stages have a better response than sinus.

16.
Clin Nutr ; 40(8): 4830-4837, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34358823

RESUMO

BACKGROUND & AIMS: Increasing data suggests that chronic low-grade inflammation plays an important role on development of sarcopenia. The present study was designed to identify the association between fibrinogen, fibrin degradation products (FDP) and sarcopenia risk in hospitalized old patients. METHODS: A total of 437 patients were enrolled in this cross-sectional study (148 with sarcopenia and 289 without sarcopenia). Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia (AWGS) 2019 criteria. Body composition, grip strength and gait speed were performed to participants. Fibrinogen, FDP levels were measured. Logistic regression analyses were carried out to assess the association between fibrinogen and sarcopenia, between FDP and sarcopenia, respectively. RESULTS: Compared to non-sarcopenic patients, fibrinogen and FDP levels were found to be higher in the sarcopenic group (3.07 g/L vs 2.79 g/L, 1.75 µg/mL vs 1.00 µg/mL, respectively, p < 0.05). Multiple linear regression analysis showed a significant negative association between fibrinogen and gait speed (ß: -0.164, p = 0.008), and muscle strength (ß: -0.231, p < 0.001). Multivariable logistic regression analysis showed that fibrinogen and FDP were independently associated with sarcopenia (odds ratio 1.32 [95% confidence interval 1.03, 1.70], p = 0.009; odds ratio 1.07 [95% confidence interval 1.01, 1.19], p = 0.049, respectively). ROC curve revealed that the cutoff values of fibrinogen and FDP to predict sarcopenia risk were 2.54 g/L and 1.15 µg/mL, respectively. CONCLUSIONS: In hospitalized old patients, serum fibrinogen and FDP levels are elevated in sarcopenia patients than those without sarcopenia. Fibrinogen and FDP are associated with sarcopenia in a concentration-dependent manner.

17.
PLoS Med ; 18(8): e1003731, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34339416

RESUMO

BACKGROUND: There remains uncertainty about the impact of menopausal hormone therapy (MHT) on women's health. A systematic, comprehensive assessment of the effects on multiple outcomes is lacking. We conducted an umbrella review to comprehensively summarize evidence on the benefits and harms of MHT across diverse health outcomes. METHODS AND FINDINGS: We searched MEDLINE, EMBASE, and 10 other databases from inception to November 26, 2017, updated on December 17, 2020, to identify systematic reviews or meta-analyses of randomized controlled trials (RCTs) and observational studies investigating effects of MHT, including estrogen-alone therapy (ET) and estrogen plus progestin therapy (EPT), in perimenopausal or postmenopausal women in all countries and settings. All health outcomes in previous systematic reviews were included, including menopausal symptoms, surrogate endpoints, biomarkers, various morbidity outcomes, and mortality. Two investigators independently extracted data and assessed methodological quality of systematic reviews using the updated 16-item AMSTAR 2 instrument. Random-effects robust variance estimation was used to combine effect estimates, and 95% prediction intervals (PIs) were calculated whenever possible. We used the term MHT to encompass ET and EPT, and results are presented for MHT for each outcome, unless otherwise indicated. Sixty systematic reviews were included, involving 102 meta-analyses of RCTs and 38 of observational studies, with 102 unique outcomes. The overall quality of included systematic reviews was moderate to poor. In meta-analyses of RCTs, MHT was beneficial for vasomotor symptoms (frequency: 9 trials, 1,104 women, risk ratio [RR] 0.43, 95% CI 0.33 to 0.57, p < 0.001; severity: 7 trials, 503 women, RR 0.29, 95% CI 0.17 to 0.50, p = 0.002) and all fracture (30 trials, 43,188 women, RR 0.72, 95% CI 0.62 to 0.84, p = 0.002, 95% PI 0.58 to 0.87), as well as vaginal atrophy (intravaginal ET), sexual function, vertebral and nonvertebral fracture, diabetes mellitus, cardiovascular mortality (ET), and colorectal cancer (EPT), but harmful for stroke (17 trials, 37,272 women, RR 1.17, 95% CI 1.05 to 1.29, p = 0.027) and venous thromboembolism (23 trials, 42,292 women, RR 1.60, 95% CI 0.99 to 2.58, p = 0.052, 95% PI 1.03 to 2.99), as well as cardiovascular disease incidence and recurrence, cerebrovascular disease, nonfatal stroke, deep vein thrombosis, gallbladder disease requiring surgery, and lung cancer mortality (EPT). In meta-analyses of observational studies, MHT was associated with decreased risks of cataract, glioma, and esophageal, gastric, and colorectal cancer, but increased risks of pulmonary embolism, cholelithiasis, asthma, meningioma, and thyroid, breast, and ovarian cancer. ET and EPT had opposite effects for endometrial cancer, endometrial hyperplasia, and Alzheimer disease. The major limitations include the inability to address the varying effects of MHT by type, dose, formulation, duration of use, route of administration, and age of initiation and to take into account the quality of individual studies included in the systematic reviews. The study protocol is publicly available on PROSPERO (CRD42017083412). CONCLUSIONS: MHT has a complex balance of benefits and harms on multiple health outcomes. Some effects differ qualitatively between ET and EPT. The quality of available evidence is only moderate to poor.

18.
J Am Chem Soc ; 143(31): 12335-12344, 2021 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-34340309

RESUMO

The efficient stereoselective synthesis of conjugated dienes, especially those with axial chirality, remains a great challenge. Herein, we report the highly atroposelective synthesis of axially chiral styrenes with a conjugated 1,3-diene scaffold via a Pd(II)-catalyzed thioether-directed alkenyl C-H olefination strategy. This strategy features easy operation, mild reaction conditions, high functional group tolerance (69 examples), complete Z-selectivity, and excellent enantioselectivities (up to 99% ee). Notably, the highly enantioselective synthesis of atropisomers with two stereogenic axes were also achieved using this strategy (up to 99% ee and 97:3 dr). Moreover, the reaction could be scaled up, and the resulting axially chiral styrenes could be easily oxidized into chiral sulfoxide derivatives with high diastereoselectivities, which showed great promise as a new type of sulfur-olefin ligand.

19.
Artigo em Inglês | MEDLINE | ID: mdl-34453416

RESUMO

Tadalafil is an effective, reversible, and competitive phosphodiesterase 5 inhibitor mainly used to treat erectile dysfunction. This study investigated the bioequivalence of generic and marketed formulations of 10-mg tadalafil tablets under fasted and fed conditions. This open-label, randomized, single-dose, 2-period crossover study included 53 healthy Chinese men (aged 20-43 years). Plasma samples were collected from 0.5 hours before treatment to 72 hours after each dose and analyzed using ultra-high-performance liquid chromatography coupled with tandem mass spectrometry. Pharmacokinetic parameters were calculated using noncompartmental analysis. Safety assessments were performed throughout the study. For the fasted state, the 90% confidence intervals of the geometric mean ratios between the generic and marketed formulations were 86.1% to 99.1% for the maximum plasma concentration and 88.4% to 100.3% for the area under the plasma concentration-time curve from time 0 to infinity, and the corresponding values under the fed state were and 99.9% to 108.4% and 95.7% to 104.3%, respectively. All data were within the accepted bioequivalence range of 80% to 125%. After consuming high-fat, high-calorie meals in the fed condition, the time to the maximum plasma concentration was similar between the formulations, and area under the plasma concentration-time curve from time 0 to infinity and maximum plasma concentration were 10.2% and 6.55% higher, respectively, for the marketed formulation. Thus, food had no clinically relevant effect on tadalafil exposure following a single oral dose in healthy Chinese men. No serious adverse reactions were reported. These results indicated that the analyzed generic and marketed tadalafil tablets were bioequivalent with similar safety profiles.

20.
Explore (NY) ; 2021 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-34417112

RESUMO

INTRODUCTION: There is currently no established effective treatment for primary Sjögren's syndrome (pSS). Traditional Chinese Medicine (TCM) is widely used in China and is reported to improve patient symptoms. This study compare the clinical efficacy and safety of herbal decoction CheReCunJin alone and combined with hydroxychloroquine for the treatment of pSS. METHODS: Seventy pSS patients without visceral involvement were randomly assigned in equal numbers to oral administration of CheReCunJin decoction only (group 1) or CheReCunJin decoction combined with hydroxychloroquine (group 2), Efficacy was evaluated after 3 months of treatment by the TCM syndrome and total effectiveness scores, European League Against Rheumatism (EULAR) Sjögren's Syndrome Patient Reported Index (ESSPRI), and Sjögren's Syndrome Disease Activity Index (ESSDAI), Schirmer's test, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and immunoglobulin G (IgG) levels. Safety was assessed. RESULTS: There were no differences in the baseline characteristics of the two groups. Compared with baseline values, the TCM syndrome, ESSPRI and ESSDAI scores, ESR, CRP, and Schirmer's test results improved significantly in both groups after treatment (p < 0.05). There was no significant difference in the TCM syndrome total effectiveness rate between the two groups (p = 0.31). Between-group differences in the changes in ESSPRI, ESSDAI, ESR, CRP, Schirmer's test, and IgG after treatment were not significant (all p> 0.05). Adverse reactions were reported in 5.88% of group 1 and 3.33% of group 2 participants (p = 0.83). CONCLUSION: CheReCunJin decoction alone was effective and safe for the treatment of pSS. TRIAL REGISTRATION: Chinese Clinical Trial Registry: ChiCTR1800016471.

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