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1.
Cancer ; 2021 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-33974715

RESUMO

BACKGROUND: There is a paucity of global comparative trend analyses of all human papillomavirus (HPV)-attributable cancers. In addition, most analyses by international sources only describe past trends; few studies have projected the future trend of HPV-attributable cancers. METHODS: Data were used from the Cancer Incidence in Five Continents (CI5plus) database that contains annual incidence by cancer site, age, and sex, as well as corresponding populations. Age-standardized HPV-attributable cancer incidence rates were calculated and plotted from 1990 through 2012. A Bayesian age-period-cohort model was used to project the HPV-attributable cancer incidence rates of each country up to 2030. RESULTS: A significant but small decreasing trend worldwide in the HPV-attributable cancer incidence rate was observed with an average annual percent change (AAPC) of -0.3 (95% CI, -0.6 to -0.1). Notably, Uganda had a consistently increasing trend of HPV-attributable cancer incidence rate, with an AAPC of 1.7 (95% CI, 0.6-2.9). U-shaped trends were observed in some high-income countries because of a recent increase in oral cavity and oropharyngeal cancers. Most countries experience a decreasing or stable trend in HPV-attributable cancers incidence rates between 1990 and 2030. However, Japan, the United Kingdom, the Netherlands, Italy, Costa Rica, and Uganda will have an increasing trend during the projection period. CONCLUSIONS: Analyses revealed favorable downward trends in HPV-attributable cancer incidence rates in most of the included countries. However, the persistently increasing trend in HPV-attributable cancer incidence rates in Uganda and the recent increase in oral cavity and oropharyngeal cancer incidence rates in some high-income countries may present a new challenge for global HPV-attributable cancer prevention. LAY SUMMARY: Analyses revealed favorable downward trends in human papillomavirus (HPV)-attributable cancer incidence rates in most of the included countries. However, the persistently increasing trend in HPV-attributable cancer incidence rates in Uganda and the recent increase in oral cavity and oropharyngeal cancer incidence rates in some high-income countries may present a new challenge for global HPV-attributable cancer prevention.

2.
Nanoscale ; 2021 May 06.
Artigo em Inglês | MEDLINE | ID: mdl-33954324

RESUMO

Correction for 'Seaming the interfaces between topologically distinct metal-organic frameworks using random copolymer glues' by Fang Wang et al., Nanoscale, 2019, 11, 2121-2125, DOI: 10.1039/C8NR09777A.

3.
Med Sci Monit ; 27: e929708, 2021 Apr 11.
Artigo em Inglês | MEDLINE | ID: mdl-33839733

RESUMO

BACKGROUND Since the outbreak of COVID-19 in December 2019, there have been 96 623 laboratory-confirmed cases and 4784 deaths by December 29 in China. We aimed to analyze the risk factors and the incidence of thrombosis from patients with confirmed COVID-19 pneumonia. MATERIAL AND METHODS Eighty-eight inpatients with confirmed COVID-19 pneumonia were reported (31 critical cases, 33 severe cases, and 24 common cases). The thrombosis risk factor assessment, laboratory results, ultrasonographic findings, and prognoses of these patients were analyzed, and compared among groups with different severity. RESULTS Nineteen of the 88 cases developed DVT (12 critical cases, 7 severe cases, and no common cases). In addition, among the 18 patients who died, 5 were diagnosed with DVT. Positive correlations were observed between the increase in D-dimer level (≥5 µg/mL) and the severity of COVID-19 pneumonia (r=0.679, P<0.01), and between the high Padua score (≥4) and the severity (r=0.799, P<0.01). In addition, the CRP and LDH levels on admission had positive correlations with the severity of illness (CRP: r=0.522, P<0.01; LDH: r=0.600, P<0.01). A negative correlation was observed between the lymphocyte count on admission and the severity of illness (r=-0.523, P<0.01). There was also a negative correlation between the lymphocyte count on admission and mortality in critical patients (r=-0.499, P<0.01). Univariable logistic regression analysis showed that the occurrence of DVT was positively correlated with disease severity (crude odds ratio: 3.643, 95% CI: 1.218-10.896, P<0.05). CONCLUSIONS Our report illustrates that critically or severely ill patients have an associated high D-dimer value and high Padua score, and illustrates that a low threshold to screen for DVT may help improve detection of thromboembolism in these groups of patients, especially in asymptomatic patients. Our results suggest that early administration of prophylactic anticoagulant would benefit the prognosis of critical patients with COVID-19 pneumonia and would likely reduce thromboembolic rates.


Assuntos
/complicações , Produtos de Degradação da Fibrina e do Fibrinogênio/análise , Trombose Venosa/epidemiologia , Adulto , Idoso , Doenças Assintomáticas , /diagnóstico , China/epidemiologia , Feminino , Mortalidade Hospitalar , Humanos , Incidência , Extremidade Inferior/irrigação sanguínea , Extremidade Inferior/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Admissão do Paciente , Prognóstico , Estudos Retrospectivos , Medição de Risco/métodos , Medição de Risco/estatística & dados numéricos , Fatores de Risco , Índice de Gravidade de Doença , Ultrassonografia , Trombose Venosa/sangue , Trombose Venosa/diagnóstico , Trombose Venosa/etiologia
4.
Environ Sci Technol ; 55(8): 4440-4451, 2021 04 20.
Artigo em Inglês | MEDLINE | ID: mdl-33793238

RESUMO

Pig production contributes considerably to land use and greenhouse gas (GHG) and reactive nitrogen (Nr) emissions. Land use strategies were widely proposed, but the spillover effects on biological flow are rarely explored. Here, we simultaneously assessed the carbon (C), nitrogen (N), and cropland footprints of China's pig production at the provincial scale in 2017. The environmental impacts of land use strategies were further evaluated. Results show that one kg live-weight pig production generated an average of 1.9 kg CO2-equiv and 59 g Nr emissions, occupying 3.5 m2 cropland, with large regional variations. A large reduction in GHG (58-64%) and Nr (12-14%) losses and occupied cropland (10-11%) could be achieved simultaneously if combined strategies of intensive crop production, improved feed-protein utilization efficiency, and feeding co-products were implemented. However, adopting a single strategy may have environmental side-effects. Reallocating cropland that pigs used for feed to plant food alternatives would enhance human-edible energy (3-20 times) and protein delivery (1-5 times) and reduce C and N footprints, except for rice and vegetables. Reallocating cropland to beef and milk production would decrease energy and protein supply. Therefore, a proper combination of land use strategies is essential to alleviate land use changes and nutrient emissions without sacrificing food supply.


Assuntos
Efeito Estufa , Gases de Efeito Estufa , Animais , Pegada de Carbono , Bovinos , China , Gases de Efeito Estufa/análise , Nitrogênio/análise , Suínos
5.
Mater Sci Eng C Mater Biol Appl ; 123: 111982, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33812610

RESUMO

Herein, a cost-effective and scalable ultrasound assisted approach was proposed to prepare the nanocomposite of halloysite nanotubes/zirconia/carbon black (Hal/ZrO2/CB), which was used to fabricate a novel electrochemical sensor for the highly sensitive determination of methyl parathion (MP). In the Hal/ZrO2/CB nanocomposite, Hal with large specific surface area and numerous active sites could enhance the adsorption capacity and accelerate the redox reaction of MP; ZrO2 nanoparticles with high affinity toward the phosphate group could contribute to good recognition performance for MP; CB nanoparticles with good dispersibility formed an interconnected pearl-chain-like conductive network. Benefitting from the synergistic effect of the three components, the Hal/ZrO2/CB/GCE (glassy carbon electrode) sensor showed a remarkably low detection limit of 5.23 nM in a good linear MP detection range of 0.01-10 µM. The Hal/ZrO2/CB/GCE sensor possessed a pretty decent practicality with satisfactory RSD and recovery results for the determination of MP in peach, pear, and apple juices. Therefore, the Hal/ZrO2/CB/GCE sensor has important implication on the quite sensitive detection of MP.

6.
Int Immunopharmacol ; 95: 107529, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33744777

RESUMO

Sepsis is a systemic inflammatory response syndrome resulted from severe infection. Excessive inflammation response plays an important role in sepsis-induced acute lung injury (ALI). Loganin is an iridoid glycoside isolated from Corni fructus and exerts an anti-inflammatory effect in multiple inflammatory diseases; however, the role of loganin in sepsis-induced ALI remains unknown. In the current study, the cecal ligation and puncture (CLP)-induced murine sepsis model was constructed to investigate the anti-inflammatory property of loganin in sepsis-induced ALI. Lipopolysaccharide (LPS)-treated Raw 264.7 cells and primary murine peritoneal macrophages were established to further explore underlying mechanism of loganin. Results showed that intragastrical administration of loganin significantly increased murine survival, reduced the alveolar structure damage and inflammatory cell infiltration. Loganin suppressed the release of the M1 macrophage-associated pro-inflammatory cytokines and induced the activation of M2-type anti-inflammatory cytokines. Besides, loganin dramatically inhibited NLRP3 inflammasome-mediated caspase-1 activation and subsequent IL-1ß secretion. Further in vitro studies confirmed that loganin efficiently inhibited M1 macrophage polarization and NLRP3 inflammasome activation by blocking the extra-cellular signal-regulated kinase (ERK) and nuclear factor-kappa B (NF-κB) pathways. Taken together, the anti-inflammatory effect of loganin in sepsis-induced ALI was associated with the ERK and NF-κB pathway-mediated macrophage polarization and NLRP3 inflammasome activation. Our study offers a favorable mechanistic basis to support the therapeutic potential of loganin in anti-inflammatory diseases, such as sepsis-induced ALI.

8.
Anal Chim Acta ; 1155: 338351, 2021 Apr 22.
Artigo em Inglês | MEDLINE | ID: mdl-33766323

RESUMO

Rapid and sensitive detection of Hg2+ in the environment and drinking water is vital because of its non-degradability, bioaccumulation, and high toxicity. Herein, we report a portable evanescent wave optofluidic biosensor (EWOB) for simple sensitive detection of Hg2+ using fluorescence labeled poly-A DNA strand (CY-A14) and quencher labeled poly-T DNA strand (BQ-T14) as signal reporter and biorecognition element, respectively. Both CY-A14 and Hg2+ can competitively bind with BQ-T14 based on DNA hybridization and the specifical binding of Hg2+ and T bases of DNA to form T-Hg2+-T mismatch structure, respectively. Higher concentration of Hg2+ lead to less CY-A14 bound to BQ-T14 and thus a higher fluorescence intensity. The influence of several key environmental factors on Hg2+ biosensor, such as pH, temperature, and ionic strength, was investigated in details because they were essential for practical applications of Hg2+ biosensor. Under optimal conditions, a detection cycle for a single sample, including the measurement and regeneration, was less than 10 min with a Hg2+ detection limit of 8.5 nM. The high selectivity of the biosensor was showed by evaluating its response to various potentially interfering metal ions. Our results clearly demonstrated that the portable EWOB could serve as a powerful tool for rapid and sensitive on-site detection of Hg2+ in real water samples. The EWOB is also potentially applicable to detect other heavy metal ions or small molecule targets for which DNA/aptamers could be applied as specific biosensing probes.

9.
Gastroenterology ; 2021 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-33744306

RESUMO

BACKGROUND & AIMS: The long-term trend in gastric cancer rates has rarely been reported from a global perspective. We aimed to explore the past temporal trends (1988-2012) in gastric cancer incidence rates in 43 countries and to predict future trends (2012-2030). METHODS: Data on yearly gastric cancer incidence by age group and sex were drawn from 108 cancer registries in 43 countries in the CI5plus database. Age-standardized incidence rates (ASRs) per 100,000 persons were computed from 1988 to 2012. The number of new cases and incidence rates were predicted to 2030 using the Bayesian age-period-cohort (BAPC) model. RESULTS: Persistent decreasing trends in gastric cancer incidence rates were observed from 1988 to 2012 worldwide, with an overall average annual percent change (AAPC) of -2.1% (95% CI: -2.5, -1.7). The trends will continue or remain stable until 2030 in most of the selected countries except for Ecuador and Lithuania, whose gastric cancer incidence rates will experience substantially increasing trends in the next several decades. CONCLUSION: The incidence rates of gastric cancer are expected to decrease through 2030 in most countries except Ecuador and Lithuania. Reductions in smoking and H. pylori prevalence and improvement in diet probably contributed to the decrease. Gastric cancer still represents a major cancer burden worldwide, and the large number of gastric cancer cases worldwide may still call for lifestyle interventions in terms of smoking and diet and massive efforts for H. pylori screening and treatment, especially in countries with predicted increasing incidence rates of gastric cancer.

10.
Nucl Med Biol ; 94-95: 98-105, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33621898

RESUMO

OBJECTIVE: Studies have confirmed that tumorigenesis is related to an imbalance of polyamine metabolism and over-expression of oncogenes resulting in the up-regulation of ornithine decarboxylase (ODC, the first rate-limiting enzyme for regulating intracellular polyamines biosynthesis), which has become a target for anti-tumor therapy. In this study, an ornithine derivative, N5-(2-[18F]fluoropropionyl) ornithine (N5-[18F]FPO), has been prepared and its potential utility for tumor PET imaging evaluated. METHODS: N5-[18F]FPO was successfully prepared via a nucleophilic fluorination reaction and a subsequent efficient deprotection step. The in vitro and in vivo stability were determined by HPLC conducted in fetal bovine serum, saline and rat urine. Cellular uptake studies were conducted in HepG2 cells and the biodistribution and micro-PET/CT imaging performed in normal ICR mice and three tumor-bearing mice models, respectively. RESULTS: Total synthesis time of N5-[18F]FPO was about 80 min with a radiochemical yield of 15% ± 6% (uncorrected, based on 18F-, n = 6) and a high radiochemical stability can be seen in vitro and vivo. The N5-[18F]FPO exhibited fast uptake in HepG2 cells and the cellular uptake ability of N5-[18F]FPO can be inhibited by L-ornithine and DFMO, which indicated that the transport pathway of N5-[18F]FPO is similar to that of L-ornithine, interacting with ODC after being transported into the cell. The biodistribution and micro-PET/CT images demonstrate that N5-[18F]FPO was excreted by the urinary system, and excellent tumor visualization with high tumor-to-background ratios can be observed in the three tumor-bearing mice models studied. CONCLUSION: All the above results suggest that N5-[18F]FPO has the potential to be a novel radiotracer for imaging ODC expression in solid tumors.

11.
J Hazard Mater ; 413: 125303, 2021 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-33582463

RESUMO

Tobacco is a super-enriched plant for heavy metals, and its productivity is sensitively affected by Cd. In this study, tobacco stalk was converted to biochar (TS-biochar) for the sequestration of Cd in soils to enhance the productivity of tobacco. FTIR, SEM-EDX, and XPS characterizations of TS-biochar together with Cd2+ adsorption kinetics revealed that oxy-containing functional groups (‒OH, CË­O, and ‒COOH) in TS-biochar played a crucial role on Cd2+ adsorption. The changes of soil property and Cd speciation by adding TS-biochar in red (acidic) and cinnamon (alkaline) soils was evaluated. Effects of TS-biochar on tobacco growth and development under Cd stress was also investigated. Results indicated that a 2 wt% addition of TS-biochar in red soil could significantly increase the soil pH value (from 5.21 to 7.39) and reduce exchangeable Cd fractions (from 40% to 23%), but those were not obvious in cinnamon soil. Under the stress of Cd, TS-biochar could obviously improve the tobacco dry biomass, and decrease the accumulation of Cd in the middle and upper leaves, thus reducing economic loss. Overall, the application of TS-biochar on Cd contaminated soil can transform bioavailable Cd into low hazardous forms, so as to repair soils and improve the productivity of tobacco.

12.
J Am Chem Soc ; 143(8): 3081-3085, 2021 Mar 03.
Artigo em Inglês | MEDLINE | ID: mdl-33591177

RESUMO

Selective separation of phenanthrene (PHE) from aromatic isomer mixtures is a big challenge in industry. In this work, a light-responsive water-soluble azobenzene-based macrocycle 1 is synthesized and an aqueous solution of E,E-1 is employed to separate PHE from anthracene via a solid-liquid extraction method under ambient conditions. After five extraction cycles, the average purity for PHE is about 91.1% and macrocycle 1 can be reused at least five times without obvious reduction of separation performance for PHE. This work not only comprises a new and clean way to separate PHE by taking advantage of a macrocyclic host but also promotes the application of host-guest chemistry.

14.
Biomol NMR Assign ; 15(1): 103-106, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33398628

RESUMO

Bacterial sigma (σ) factor, along with RNA polymerase core enzyme, initiates gene transcription from specific promoter regions and therefore regulates clusters of genes in response to a particular situation. The extracytoplasmic function (ECF) σ factors are a class of alternative σ factors that are often associated with environmental signal transduction across the bacterial membrane, in which external signal triggers the release of active σ from the membrane-anchored anti-σ factor. Gram-positive model organism Bacillus subtilis (B. subtilis) has seven ECF σ factors: σM, σV, σX, σW, σY, σZ and σYlaC. Although all these ECF σ factors were found to be involved in B. subtilis antibiotic resistance, σW is among the most studied and considered to play a pivotal role in responding to antimicrobial stresses. σW is under tight control and remains deactivated until exposure to external stimuli, after which proteases PrsW and RasP cleave the specific anti-sigma factor-RsiW to release and activate σW. Membrane anchored protein YsdB is a negative regulator of this activation, possibly via its direct interaction with PrsW and/or RsiW. Importantly, YsdB is well conserved among Bacilli, including pathogenic bacteria like Bacillus cereus. In this study, we describe the chemical shift assignments of the cytoplasmic domain of YsdB (29-130) of B. subtilis in solution as a basis for further interaction studies and structure determination. The near-complete assignment and the solution structure that will follow could provide a further understanding in σW regulation.

15.
Molecules ; 26(2)2021 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-33477555

RESUMO

13a-(S)-3-pivaloyloxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (CAT3) is a novel oral anti-glioma pro-drug with a potent anti-tumor effect against temozolomide-resistant glioma. 13a(S)-3-hydroxyl-6,7-dimethoxyphenanthro(9,10-b)-indolizidine (PF403) is the active in vivo lipase degradation metabolite of CAT3. Both CAT3 and PF403 can penetrate the blood-brain barrier to cause an anti-glioma effect. However, PF403, which is produced in the gastrointestinal tract and plasma, causes significant gastrointestinal side effects, limiting the clinical application of CAT3. The objective of this paper was to propose a metabolism modification for CAT3 using a self-microemulsifying drug delivery system (SMEDDS), in order to reduce the generation of PF403 in the gastrointestinal tract and plasma, as well as increase the bioavailability of CAT3 in vivo and the amount of anti-tumor substances in the brain. Thus, a CAT3-loaded self-microemulsifying drug delivery system (CAT3-SMEDDS) was prepared, and its physicochemical characterization was systematically carried out. Next, the pharmacokinetic parameters of CAT3 and its metabolite in the rats' plasma and brain were measured. Furthermore, the in vivo anti-glioma effects and safety of CAT3-SMEDDS were evaluated. Finally, Caco-2 cell uptake, MDCK monolayer cellular transfer, and the intestinal lymphatic transport mechanisms of SMEDDS were investigated in vitro and in vivo. Results show that CAT3-SMEDDS was able to form nanoemulsion droplets in artificial gastrointestinal fluid within 1 min, displaying an ideal particle size (15-30 nm), positive charge (5-9 mV), and controlled release behavior. CAT3-SMEDDS increased the membrane permeability of CAT3 by 3.9-fold and promoted intestinal lymphatic transport. Hence, the bioavailability of CAT3 was increased 79% and the level of its metabolite, PF403, was decreased to 49%. Moreover, the concentrations of CAT3 and PF403 were increased 2-6-fold and 1.3-7.2-fold, respectively, in the brain. Therefore, the anti-glioma effect in the orthotopic models was improved with CAT3-SMEDDS compared with CAT3 in 21 days. Additionally, CAT3-SMEDDS reduced the gastrointestinal side effects of CAT3, such as severe diarrhea, necrosis, and edema, and observed less inflammatory cell infiltration in the gastrointestinal tract, compared with the bare CAT3. Our work reveals that, through the metabolism modification effect, SMEDDS can improve the bioavailability of CAT3 and reduce the generation of PF403 in the gastrointestinal tract and plasma. Therefore, it has the potential to increase the anti-glioma effect and reduce the gastrointestinal side effects of CAT3 simultaneously.

16.
J Mol Biol ; 433(3): 166757, 2021 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-33346011

RESUMO

Regulation of bacterial stress responding σS is a sophisticated process and mediated by multiple interacting partners. Controlled proteolysis of σS is regulated by RssB which maintains minimal level of σS during exponential growth but then elevates σS level while facing stresses. Bacteria developed different strategies to regulate activity of RssB, including phosphorylation of itself and production of anti-adaptors. However, the function of phosphorylation is controversial and the mechanism of anti-adaptors preventing RssB-σS interaction remains elusive. Here, we demonstrated the impact of phosphorylation on the activity of RssB and built the RssB-σS complex model. Importantly, we showed that the phosphorylation site - D58 is at the interface of RssB-σS complex. Hence, mutation or phosphorylation of D58 would weaken the interaction of RssB with σS. We found that the anti-adaptor protein IraD has higher affinity than σS to RssB and its binding interface on RssB overlaps with that for σS. And IraD-RssB complex is preferred over RssB-σS in solution, regardless of the phosphorylation state of RssB. Our study suggests that RssB possesses a two-tier mechanism for regulating σS. First, phosphorylation of RssB provides a moderate and reversible tempering of its activity, followed by a specific and robust inhibition via the anti-adaptor interaction.


Assuntos
Fenômenos Fisiológicos Bacterianos , Proteínas de Bactérias/metabolismo , Proteínas de Ligação a DNA/metabolismo , Proteínas de Escherichia coli/metabolismo , Fator sigma/metabolismo , Fatores de Transcrição/metabolismo , Proteínas de Bactérias/química , Sítios de Ligação , Proteínas de Ligação a DNA/química , Proteínas de Escherichia coli/química , Modelos Biológicos , Modelos Moleculares , Fosforilação , Ligação Proteica , Conformação Proteica , Proteólise , Fator sigma/química , Relação Estrutura-Atividade , Fatores de Transcrição/química
17.
Bioorg Chem ; 107: 104523, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33339668

RESUMO

Chuanxiongdiolides R4-R6 (1-3), three novel phthalide dimers featuring two classes of unreported monomeric units (ligustilide/senkyunolide A and ligustilide/neocnidilide) with an unprecedented linkage style (3a,7'/7a,7'a), were isolated from the aerial parts of Ligusticum chuanxiong, together with three pairs of enantiomeric phthalide dimers [(-)/(+)-4a/4b, 5a/5b, and 6a/6b]. The bioassays revealed that compounds 1, 3, 4, 5, and 6 showed significant vasodilation effects, and the mechanism may be attributed to Cav1.2 activation blockade. Based on the established compounds library, the structure activity relationship of the phthalides was proposed. Our findings afford possible leads for developing new vasodilator against cardiovascular and cerebrovascular diseases such as hypertension and ischemic stroke.

18.
Artigo em Inglês | MEDLINE | ID: mdl-33295014

RESUMO

Azobenzene (azo)-based macrocycles are highly fascinating in supramolecular chemistry because of their light-responsiveness. In this work, a series of azo-based macrocyclic arenes 1 , 2 , 3 and 4 distinguished by the substituted positions of azo groups are rationally designed and synthesized via a fragment cyclization method. From the crystal and computed structures of 1 , 2 and 3 , we observe that the cavity size of these azo-macrocycles decreases gradually upon E → Z photoisomerization. Moreover, light-controlled host-guest complexations between azo-macrocycle 1 and guest molecules (7,7,8,8-tetracyanoquinodimethane, terephthalonitrile) are successfully achieved. This work provides a simple and effective method to prepare azo-macrocycles, and the light-responsive molecular encapsulation systems in this work may further advance the design and applications of novel photo-responsive host-guest systems.

19.
bioRxiv ; 2020 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-33300001

RESUMO

Coronavirus disease 2019 (COVID-19) includes the cardiovascular complications in addition to respiratory disease. SARS-CoV-2 infection impairs endothelial function and induces vascular inflammation, leading to endotheliitis. SARS-CoV-2 infection relies on the binding of Spike glycoprotein (S protein) to angiotensin converting enzyme 2 (ACE2) in the host cells. We show here that S protein alone can damage vascular endothelial cells (ECs) in vitro and in vivo, manifested by impaired mitochondrial function, decreased ACE2 expression and eNOS activity, and increased glycolysis. The underlying mechanism involves S protein downregulation of AMPK and upregulation of MDM2, causing ACE2 destabilization. Thus, the S protein-exerted vascular endothelial damage via ACE2 downregulation overrides the decreased virus infectivity.

20.
Zhonghua Nan Ke Xue ; 26(7): 611-615, 2020 Jul.
Artigo em Chinês | MEDLINE | ID: mdl-33377716

RESUMO

Objective: To observe the clinical effect of priligy (dapoxetine hydrochloride) combined with behavioral therapy and psychological counseling in the treatment of primary premature ejaculation (PPE). METHODS: A total of 202 PPE patients diagnosed from 2017 to 2018 were randomized into a control (n = 100) and an experimental group (n = 102), the former treated with oral priligy at 30 mg 1-3 hours before anticipated sexual activity, and the latter by the same medication combined with 30-minute behavioral therapy and psychological counseling once a month for two times. The therapeutic effects were evaluated according to the Premature Ejaculation Profile (PEP) scores of the patients at 1 and 2 months of treatment. RESULTS: After 1 month of treatment, both groups of the patients showed significant improvement, as compared with the baseline, in the PEP scores on personal distress related to ejaculation (P < 0 05), interpersonal difficulty related to ejaculation (P < 0.05) and satisfaction with sexual intercourse (P < 0.05) but not on perceived control over ejaculation (P > 0.05). At 2 months, however, the patients' scores on all the four PEP items were dramatically improved, even more significantly in the experimental than in the control group, as on perceived control over ejaculation (2.73 ± 0.95 vs 2.22 ± 0.68, P < 0.05), personal distress related to ejaculation (2.97 ± 1.07 vs 2.57 ± 0.69, P < 0.05), interpersonal difficulty related to ejaculation (3.19 ± 1.03 vs 2.77 ± 0.69, P < 0 05) and satisfaction with sexual intercourse (2.85 ± 0.99 vs 2.35 ± 0.63, P < 0.05). There was no statistically significant difference in the incidence rate of adverse events between the experimental and control groups (21.6% vs 20.0%, P > 0.05), and all the symptoms were relieved within 24 hours. CONCLUSIONS: Priligy combined with behavioral therapy and psychological counseling is more effective than priligy alone in improving the sexual function of PPE patients, raise their interest in sexual life and increase the intimacy between the partners, and can even achieve clinical cure in some patients.


Assuntos
Benzilaminas/uso terapêutico , Terapia Cognitivo-Comportamental , Naftalenos/uso terapêutico , Ejaculação Precoce , Psicoterapia , Inibidores de Captação de Serotonina/uso terapêutico , Humanos , Masculino , Ejaculação Precoce/terapia , Resultado do Tratamento
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