Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 679
Filtrar
1.
BMC Cancer ; 22(1): 11, 2022 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-34979982

RESUMO

BACKGROUND: The mixed-lineage leukemia (MLL) gene is located on chromosome 11q23. The MLL gene can be rearranged to generate partial tandem duplications (MLL-PTD), which occurs in about 5-10% of acute myeloid leukemia (AML) with a normal karyotype and in 5-6% of myelodysplastic syndrome (MDS) patients. Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is currently one of the curative therapies available for AML and MDS with excess blasts (MDS-EB). However, how the prognosis of patients with high levels of MLL-PTD after allo-HSCT, and whether MLL-PTD could be used as a reliable indicator for minimal residual disease (MRD) monitoring in transplant patients remains unknown. Our study purposed to analyze the dynamic changes of MLL-PTD peri-transplantation and the best threshold for predicting relapse after transplantation. METHODS: We retrospectively collected the clinical data of 48 patients with MLL-PTD AML or MDS-EB who underwent allo-HSCT in Peking University People's Hospital. The MLL-PTD was examined by real-time quantitative polymerase chain reaction (RQ-PCR) at the diagnosis, before transplantation and the fixed time points after transplantation. Detectable MLL-PTD/ABL > 0.08% was defined as MLL-PTD positive in this study. RESULTS: The 48 patients included 33 AML patients and 15 MDS-EB patients. The median follow-up time was 26(0.7-56) months after HSCT. In AML patients, 7 patients (21.2%) died of treatment-related mortality (TRM), 6 patients (18.2%) underwent hematological relapse and died ultimately. Of the 15 patients with MDS-EB, 2 patients (13.3%) died of infection. The 3-year cumulative incidence of relapse (CIR), overall survival (OS), disease-free survival (DFS) and TRM were 13.7 ± 5.2, 67.8 ± 6.9, 68.1 ± 6.8 and 20.3% ± 6.1%, respectively. ROC curve showed that post-transplant MLL-PTD ≥ 1.0% was the optimal cut-off value for predicting hematological relapse after allo-HSCT. There was statistical difference between post-transplant MLL-PTD ≥ 1.0% and MLL-PTD < 1.0% groups (3-year CIR: 75% ± 15.3% vs. 0%, P < 0.001; 3-year OS: 25.0 ± 15.3% vs. 80.7% ± 6.6%, P < 0.001; 3-year DFS: 25.0 ± 15.3% vs. 80.7 ± 6.6%, P < 0.001; 3-year TRM: 0 vs. 19.3 ± 6.6%, P = 0.277). However, whether MLL-PTD ≥ 1% or MLL-PTD < 1% before transplantation has no significant difference on the prognosis. CONCLUSIONS: Our study indicated that MLL-PTD had a certain stability and could effectively reflect the change of tumor burden. The expression level of MLL-PTD after transplantation can serve as an effective indicator for predicting relapse.

2.
World J Pediatr ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34984641

RESUMO

BACKGROUND: This study aimed to describe length of stay (LOS) to discharge and site variations among very preterm infants (VPIs) admitted to 57 Chinese neonatal intensive care units (NICUs) and to investigate factors associated with LOS for VPIs. METHODS: This retrospective multicenter cohort study enrolled all infants < 32 weeks' gestation and admitted to 57 NICUs which had participated in the Chinese Neonatal Network, within 7 days after birth in 2019. Exclusion criteria included major congenital anomalies, NICU deaths, discharge against medical advice, transfer to non-participating hospitals, and missing discharge date. Two multivariable linear models were used to estimate the association of infant characteristics and LOS. RESULTS: A total of 6580 infants were included in our study. The overall median LOS was 46 days [interquartile range (IQR): 35-60], and the median corrected gestational age at discharge was 36 weeks (IQR: 35-38). LOS and corrected gestational age at discharge increased with decreasing gestational age. The median corrected gestational age at discharge for infants at 24 weeks, 25 weeks, 26 weeks, 27-28 weeks, and 29-31 weeks were 41 weeks, 39 weeks, 38 weeks, 37 weeks and 36 weeks, respectively. Significant site variation of LOS was identified with observed median LOS from 33 to 71 days in different hospitals. CONCLUSIONS: The study provided concurrent estimates of LOS for VPIs which survived in Chinese NICUs that could be used as references for medical staff and parents. Large variation of LOS independent of infant characteristics existed, indicating variation of care practices requiring further investigation and quality improvement.

3.
J Am Heart Assoc ; : e023053, 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34984916

RESUMO

Background cGMP-hydrolyzing phosphodiesterase type 5 (PDE5) regulates vascular smooth muscle cell (SMC) contraction by antagonizing cGMP-dependent protein kinase I (PKGI)-dependent SMC relaxation. SMC contractile dysfunction is implicated in the pathogenesis of aortic aneurysm. PDE5 inhibitors have been used for treating erectile dysfunction, such as drug Viagra (sildenafil). However, a few clinical cases have reported the association of Viagra usage with aortic dissection, and reduced PDE5A expression was found in human aortic aneurysm tissues. Therefore, we aimed to investigate the effect of sildenafil on experimental abdominal aortic aneurysm (AAA), the most common form of aortic aneurysm in elderly men. Methods and Results AAA was induced in C57BL/6J male mice by periaortic elastase in combination with blocking elastin/collagen formation via 3-aminopropionitrile fumarate salt for 35 days. PDE5A protein levels detected by immunostaining were significantly reduced in mouse AAA. Sildenafil application in drinking water significantly aggravated aortic wall dilation and elastin degradation with pre-existing moderate AAA. The phosphorylation level of myosin light chain 2 at Ser19, a biochemical marker of SMC contraction, was significantly reduced by sildenafil in AAA. Proximity ligation assay further revealed that the interaction between cGMP and PKGI was significantly increased by sildenafil in AAA, suggesting an elevation of PKGI activation in AAA. Conclusions Sildenafil treatment aggravated the degradation of elastin fibers and progression of experimental AAA by dysregulating cGMP and contractile signaling in SMCs. Our findings may raise the caution of clinical usage of Viagra in aneurysmal patients.

4.
Artigo em Inglês | MEDLINE | ID: mdl-35001470

RESUMO

The available processes for removing acetylene impurities from crude ethylene are tremendously energy-intensive. Herein, we demonstrate a novel aqueous Zn-C 2 H 2 battery, which not only switches energy-consuming acetylene removal to electricity generation, but reduces acetylene to ethylene through a unique discharge mechanism: C 2 H 2 + Zn + H 2 O → C 2 H 4 + ZnO. Under a pure acetylene stream, this Zn-C 2 H 2 battery exhibits an open circuit potential of 1.14 V and a peak power density of 2.2 mW cm -2 , which exceed those of reported Zn-CO 2 batteries. Even for simulated crude ethylene, the Zn-C 2 H 2 battery manifests an acetylene conversion of 99.97% and continuously produces polymer-grade ethylene with only ~3 ppm acetylene during a long-term discharge operation. Such a functional battery is universally appliable for reducing other alkynes and generating electricity. Therefore, this work provides an effective strategy for green ethylene purification and the design of functional batteries.

5.
J Affect Disord ; 298(Pt B): 1-9, 2022 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-34808134

RESUMO

BACKGROUND: many studies explore the relationship between social capital and self-rated health. However, few studies clarified the mechanisms underlying the relationship between social capital and self-rated health among Chinese rural empty nesters. This study aimed to explore the multiple mediating roles of sleep quality and psychological distress between this relationship. METHODS: A total of 2,254 rural empty-nest older adults were included in the analysis. A descriptive analysis was conducted to describe the sample characteristics. Logistic regressions were performed to assess the relationships between social capital and self-rated health. The multiple mediating roles of sleep quality and psychological distress was analyzed using Mplus 8.3. RESULTS: we found that social capital has a significant directly affect self-rated health (ß=0.127, 68.65% CI=0.082-0.171), and through three significantly mediation pathways: (1) the path through sleep quality (ß=0.013, 95% CI=0.005-0.021), which accounted for 7.03% of the total effect; (2) the path through psychological distress (ß=0.037, 95% CI=0.024-0.049), which accounted for 20.00% of the total effect; (3) the path through sleep quality and psychological distress (ß=0.008, 95% CI=0.004-0.013), which accounted for 4.32% of the total effect. The total mediating effect was 31.35%. CONCLUSIONS: sleep quality and psychological distress mediate the relationship between social capital and self-rated health. Attention should be paid to mental health and sleep quality of empty nester through primary health, strengthen the attention to social resources, provide intervention and treatment for the empty nesters with sleep problem and psychological distress.

6.
Molecules ; 26(23)2021 Nov 25.
Artigo em Inglês | MEDLINE | ID: mdl-34885715

RESUMO

Antibiotics played an important role in controlling the development of enteric infection. However, the emergence of antibiotic resistance and gut dysbiosis led to a growing interest in the use of natural antimicrobial agents as alternatives for therapy and disinfection. Chitosan is a nontoxic natural antimicrobial polymer and is approved by GRAS (Generally Recognized as Safe by the United States Food and Drug Administration). Chitosan and chitosan derivatives can kill microbes by neutralizing negative charges on the microbial surface. Besides, chemical modifications give chitosan derivatives better water solubility and antimicrobial property. This review gives an overview of the preparation of chitosan, its derivatives, and the conjugates with other polymers and nanoparticles with better antimicrobial properties, explains the direct and indirect mechanisms of action of chitosan, and summarizes current treatment for enteric infections as well as the role of chitosan and chitosan derivatives in the antimicrobial agents in enteric infections. Finally, we suggested future directions for further research to improve the treatment of enteric infections and to develop more useful chitosan derivatives and conjugates.

7.
Bioresour Technol ; 345: 126570, 2021 Dec 16.
Artigo em Inglês | MEDLINE | ID: mdl-34921923

RESUMO

Improving the efficiency of hydrolytic acidification is critical for methane production from agricultural waste. This study is the first to apply domesticated paddy soil microbes to (DPSM) enhance the hydrolytic acidification of rice straw (RS) and pig manure (PM) to obtain acidizing fluid for anaerobic digestion (AD). At a substrate concentration of 20%, the inoculation of an RS-PM mixture (1:3) with 35% DPSM degraded the volatile solids by 48.1% and yielded 6.8 g/L of volatile fatty acids and 4.7 g/L of acetic acid after seven days of hydrolytic acidification. After 10 days of subsequent AD, the cumulative methane production of the acidizing fluid was 304.96 mL/g COD, similar (P ï¼ž 0.05) to the control (318.27 mL/g COD). However, the methane production time decreased by 43.4% (from 30 to 17 days), thereby improving the AD efficiency. Inoculation with DPSM is therefore an effective pre-treatment for agricultural waste for methane production.

8.
Front Cell Dev Biol ; 9: 737809, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34926442

RESUMO

Intervertebral disc degeneration (IDD) has been generally accepted as the major cause of low back pain (LBP), which imposes massive clinical and socioeconomic burdens. Previous studies have demonstrated that oxidative stress and inflammation-induced senescence and apoptosis of nucleus pulposus cells (NPCs) are the main cellular processes that cause IDD. Arginase II (ARG2), an enzyme involved in a variety of pathological processes, including cellular senescence, apoptosis, oxidative stress, and inflammation, has been shown to promote degeneration in several degenerative diseases, including osteoarticular diseases. Based on previous studies, we hypothesized that ARG2 deficiency might be conducive to the treatment of IDD by inhibiting the dyshomeostasis of the extracellular matrix (ECM), and the oxidative stress and inflammatory response-induced senescence and apoptosis via NF-κB. In this study, we found that ARG2 deficiency inhibited senescence and apoptosis of NPCs, and degeneration of the ECM induced by oxidative stress and the inflammatory response. Similar results were found with the selective NF-κB pathway inhibitor JSH-23. In contrast, overexpression of ARG2 had the opposite effect. Taken together, our results suggest that ARG2 deficiency prevents IDD via NF-κB, and may therefore, be a potential therapeutic strategy for IDD.

9.
J Public Aff ; : e2760, 2021 Sep 13.
Artigo em Inglês | MEDLINE | ID: mdl-34899059

RESUMO

COVID-19 is wreaking havoc all around the globe, and Pakistan bears no exception. This study explores Pakistan's response toward controlling COVID-19 Pandemic from the day the 1st case was reported, February 26, 2020, in Pakistan until August 31, 2020. It explores the administrative conflicts among federal and provincial governments and political behaviors of political parties toward the COVID-19 pandemic by referring Government Response Index. By applying the ARDL model approach, results show that since the administrative harmony had been implemented in Pakistan in July 2020, its positive impact on combating the COVID-19 situation in Pakistan and substantial improvement in recovered cases and a downward trend new confirmed and fatal cases has observed in Pakistan. The findings demonstrate that administrative efforts scattered due to internal conflicts from February to mid-July 2020 have ended, and collective aggressive policy enforcement has been mitigating the adverse impact of COVID-19 in Pakistan since July to date. However, sustainable measures and prudent policy implications are needed to combat the ongoing COVID-19 pandemic and future calamities.

10.
Dalton Trans ; 2021 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-34787610

RESUMO

Biomass-derived carbon-based energy materials are receiving extensive attention nowadays. With the widespread use of traditional Chinese medicines in the treatment of diseases and health care, a great deal of herb residues are thrown away after the unique decoction process. Here, through hydrothermal carbonization combined with KOH activation, a micropore-rich and nitrogen-doped porous carbon framework (MRNCF) is prepared from the waste roots of a kind of well-known and widely used traditional Chinese medicine, Acanthopanax senticosus. Compared with ordinary carbon-based sulfur host materials, the MRNCFs can effectively hinder the shuttling effect and dissolution of polysulfides through the synergistic action of physical confinement in micropores and chemical anchoring for nitrogen doping, and the lithium-sulfur batteries using MRNCF as the host present superior electrochemical performance. In a high sulfur content of over 75%, the as-prepared electrodes exhibit a highly reversible specific capacity of 540.4 mA h g-1 at a current density of 0.5C after 150 cycles and an excellent rate capability at different current densities.

11.
Cell Immunol ; 371: 104452, 2021 Nov 07.
Artigo em Inglês | MEDLINE | ID: mdl-34784561

RESUMO

Atopic dermatitis (AD) is a common inflammatory skin disorder that affects children and adults. Despite the pathology of AD involves in immune dysfunction and epidermal barrier function destruction has been found, the mechanism of immune activation and barrier damage remain largely unknown. In the present study, The TNF-α/IFN-γ-stimulated HaCaTs, organotypic AD-like 3D skin equivalents and AD-like mouse model were constructed. The mRNA, histological morphology, protein levels, cytokines were detected by real-time quantitative polymerasechain reaction (RT-qPCR), hematoxylin and eosin (H & E) staining, Immunohistochemistry (IHC), immunoblotting, immunofluorescence (IF) staining, and enzyme linked immunosorbent assay (ELISA), respectively. Cell viability, cell cycle, and apoptosis were respectively calculated using a Methylthiazolyldiphenyl-tetrazolium bromide (MTT) assay and flow cytometry. A dual-luciferase reporter gene system was used to investigate the relationship between miR-1294 and STAT3. Compared with the control group, the expression of miR-1294 decreased in TNF-α/IFN-γ-stimulated HaCaTs (P < 0.001), AD-like skin model, and AD-like mouse model (P < 0.001). Moreover, STAT3 was documented as a direct target of miR-1294. Inflammation (P < 0.05) and epidermal barrier function destruction (P < 0.05) in AD was suppressed by overexpression of miR-1294 but enhanced by STAT3 upregulation and its downstream NF-κB pathway. We also found miR-1294 upregulation inhibited inflammation and epidermal barrier function destruction via targeting STAT3 to suppress NF-κB pathway activation in AD.

12.
Br J Haematol ; 2021 Nov 06.
Artigo em Inglês | MEDLINE | ID: mdl-34741461

RESUMO

Haploidentical allogeneic haematopoietic stem cell transplantation (haplo-HSCT) is a significant alternative treatment for severe aplastic anaemia (SAA). To improve this process by modifying the risk stratification system, we conducted a retrospective study using our database. 432 SAA patients who received haplo-HSCT between 2006 and 2020 were enrolled. These patients were divided into a training (n = 288) and a validation (n = 144) subset randomly. In the training cohort, longer time from diagnosis to transplantation, poorer Eastern Cooperative Oncology Group (ECOG) status and higher haematopoietic cell transplantation-specific comorbidity index (HCT-CI) score were independent risk factors for worse treatment-related mortality (TRM) in the final multivariable model. The haplo-HSCT scoring system was developed by these three parameters. Three-year TRM after haplo-HSCT were 6% [95% confidence interval (CI), 1-21%], 21% (95% CI, 7-40%), and 47% (95% CI, 20-70%) for the low-, intermediate-, and high-risk group, respectively (P < 0·0001). In the validation cohort, the haplo-HSCT scoring system also separated patients into three risk groups with increasing risk of TRM: intermediate-risk [hazard ratio (HR) 2·45, 95% CI, 0·92-6·53] and high-risk (HR 11·74, 95% CI, 3·07-44·89) compared with the low-risk group (P = 0·001). In conclusion, the haplo-HSCT scoring system could effectively predict TRM after transplantation.

13.
Front Med (Lausanne) ; 8: 770914, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34796190

RESUMO

Psychological distress were found to be associated with chronic conditions and persistent pain. However, few studies explored the underlying pathways between them. This study aimed to analyze the path of chronic conditions and persistent pain on psychological distress through sleep quality and self-rated health. A total of 2,748 rural older people in Shandong, China were included in this study. Path analysis was performed by using Mplus 8.3 to examine the associations between chronic conditions, persistent pain, sleep quality, self-rated health, and psychological distress after adjusting for age, gender, education, and household income. The prevalence of psychological distress among the older adults in this study was 47.49%. Chronic conditions and persistent pain were indirectly associated with psychological distress through six mediating pathways: (1) the path from chronic conditions to psychological distress through sleep quality (ß = 0.041, 95%CI: 0.015-0.067) and self-rated health (ß = 0.064, 95%CI: 0.038-0.091), respectively, and a chain mediation existed (ß = 0.007, 95% CI: 0.000-0.014); (2) the path of persistent pain and psychological distress through sleep quality (ß = 0.058, 95% CI: 0.014-0.102) and self-rated health (ß = 0.048, 95% CI: 0.000-0.096), respectively, also the chain mediation found (ß = 0.009, 95% CI: 0.005-0.014). Psychological distress was associated with chronic conditions and persistent pain through decreased sleep quality and self-rated health among Chinese rural older people. Multi-pronged targeted intervention should be taken for older adults with chronic conditions and persistent pain.

14.
Nat Commun ; 12(1): 6574, 2021 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-34772929

RESUMO

Electrocatalytic acetylene semihydrogenation is a promising alternative to thermocatalytic acetylene hydrogenation due to its environmental benignity and economic efficiency, but its performance is far below that of the thermocatalytic reaction because of strong competition from side reactions, including hydrogen evolution, overhydrogenation and carbon-carbon coupling reactions. We develop N-heterocyclic carbene-metal complexes, with electron-rich metal centers owing to the strongly σ-donating N-heterocyclic carbene ligands, as electrocatalysts for selective acetylene semihydrogenation. Experimental and theoretical investigations reveal that the copper sites in N-heterocyclic carbene-copper facilitate the absorption of electrophilic acetylene and the desorption of nucleophilic ethylene, ultimately suppressing the side reactions during electrocatalytic acetylene semihydrogenation, and exhibit superior semihydrogenation performance, with faradaic efficiencies of ≥98 % under pure acetylene flow. Even in a crude ethylene feed containing 1 % acetylene (1 × 104 ppm), N-heterocyclic carbene-copper affords a specific selectivity of >99 % during a 100-h stability test, continuous ethylene production with only ~30 ppm acetylene, a large space velocity of up to 9.6 × 105 mL·gcat-1·h-1, and a turnover frequency of 2.1 × 10-2 s-1, dramatically outperforming currently reported thermocatalysts.

15.
Artigo em Inglês | MEDLINE | ID: mdl-34773583

RESUMO

Access to financial services is regarded as one of the most pressing issues confronting communities worldwide sequel to the COVID-19 pandemic. In this regard, FinTech applications such as mobile financial service (MFS) play an essential role in building resilience during the pandemic. Hence, the aim of the study is to investigate the role of MFS platforms in economic resilience by empirically evaluating the determinants that influence the intention of Bangladeshi users toward adopting MFS platforms during the COVID-19 pandemic, through an extension of the Unified Theory of Acceptance and Use of Technology (UTAUT). Using the core structures of the UTAUT, the theoretical model was constructed based on the consumption attributes of financial services such as perceived value, as well as additional situational factors from the extended valence framework, including risk and trust. To test the model, data was obtained from 227 potential MFS users in Bangladesh with the aid of a structured questionnaire survey. Subsequently, the Structural Equation Modeling (SEM) approach was used to analyze the data. The findings showed that social influence, perceived trust, and perceived value are strongly related to the intention of users to adopt MFS platforms, whereas, perceived risk, performance expectancy, and effort expectancy were observed to influence users' perceived value of the MFS platforms during the COVID-19 pandemic. Interestingly, the study results indicated that the users' perceived risk did not influence their intention to adopt MFS platforms during the pandemic. Therefore, the suggested adoption of the MFS framework during and after the pandemic could contribute to the existing research on the adoption of information technology (IT) through the expansion of the UTAUT, in which the performance and effort expectancy of users influence their intention to indirectly adopt MFS through perceived value. Finally, the significant policy implications and future research directions are further addressed.

16.
Front Nutr ; 8: 756565, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34722615

RESUMO

Scope: Gut microbiome-derived metabolites are the major mediators of diet-induced host-microbial interactions. Aryl hydrocarbon receptor (AHR) plays a crucial role in glucose, lipid, and cholesterol metabolism in the liver. In this study, we aimed to investigate the role of indole-3-acetic acid (IAA) and AHR in sulforaphane (SFN) alleviates hepatic steatosis in mice fed on a high-fat diet (HFD). Methods and Results: The HFD-fed male C57BL/6 mice were intervened with SFN for 6 weeks. HFD-mice showed classical pathophysiological characteristics of hepatic steatosis. The results showed that SFN significantly reduced body weight, liver inflammation and hepatic steatosis in HFD-fed mice. SFN reduced hepatic lipogenesis by activating AHR/SREBP-1C pathway, which was confirmed in HepG2 cell experiments. Moreover, SFN increased hepatic antioxidant activity by modulating Nrf-2/NQO1 expression. SFN increased serum and liver IAA level in HFD mice. Notably, SFN manipulated the gut microbiota, resulting in reducing Deferribacteres and proportions of the phylum Firmicutes/Bacteroidetes and increasing the abundance of specific bacteria that produce IAA. Furthermore, SFN upregulated Ahr expression and decreased the expression of inflammatory cytokines in Raw264.7 cells. Conclusions: SFN ameliorated hepatic steatosis not only by modulating lipid metabolism via AHR/SREBP-1C pathway but regulating IAA and gut microbiota in HFD-induced NAFLD mice.

17.
BMC Genomics ; 22(1): 790, 2021 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-34732130

RESUMO

BACKGROUND: The complexity of physical activity (PA) and DNA methylation interaction in the development of cardiovascular disease (CVD) is rarely simultaneously investigated in one study. We examined the role of DNA methylation on the association between PA and CVD. RESULTS: The Multi-Ethnic Study of Atherosclerosis (MESA) cohort Exam 5 data with 1065 participants free of CVD were used for final analysis. The quartile categorical total PA variable was created by activity intensity (METs/week). During a median follow-up of 4.0 years, 69 participants developed CVD. Illumina HumanMethylation450 BeadChip was used to provide genome-wide DNA methylation profiles in purified human monocytes (CD14+). We identified 23 candidate DNA methylation loci to be associated with both PA and CVD. We used the structural equation modeling (SEM) approach to test the complex relationships among multiple variables and the roles of mediators. Three of the 23 identified loci (corresponding to genes VPS13D, PIK3CD and VPS45) remained as significant mediators in the final SEM model along with other covariates. Bridged by the three genes, the 2nd PA quartile (ß = - 0.959; 95%CI: - 1.554 to - 0.449) and the 3rd PA quartile (ß = - 0.944; 95%CI: - 1.628 to - 0.413) showed the greatest inverse associations with CVD development, while the 4th PA quartile had a relatively weaker inverse association (ß = - 0.355; 95%CI: - 0.713 to - 0.124). CONCLUSIONS: The current study is among the first to simultaneously examine the relationships among PA, DNA methylation, and CVD in a large cohort with long-term exposure. We identified three DNA methylation loci bridged the association between PA and CVD. The function of the identified genes warrants further investigation in the pathogenesis of CVD.


Assuntos
Aterosclerose , Doenças Cardiovasculares , Aterosclerose/genética , Doenças Cardiovasculares/genética , Metilação de DNA , Exercício Físico , Humanos , Fatores de Risco
18.
Circ Res ; 129(Suppl_1): AMP265, 2021 Sep 03.
Artigo em Inglês | MEDLINE | ID: mdl-34735298

RESUMO

Cyclic nucleotide phosphodiesterases (PDEs), through the degradation of cyclic nucleotides, play critical roles in cardiovascular biology and disease. PDE10A is able to hydrolyze both cAMP and cGMP. Its high expression in medium spiny neurons of the human striatum has led to the development of several PDE10A inhibitors with the intent to treat various psychiatric/neurodegenerative disorders, such as schizophrenia and Huntington's disease. Our previous study has reported the upregulation of PDE10A expression in failing hearts and demonstrated the protective effects of PDE10A deficiency/inhibition against cardiac hypertrophy, fibrosis, and dysfunction in mouse models of heart failure. Doxorubicin (DOX) is an effective chemotherapeutic agent against a variety of cancers. While its therapeutic utility is limited by the development of dose-dependent cardiotoxicity. In the current study, we aim to determine the role of PDE10A in cancer and cardiotoxicity induced by DOX. We found that PDE10A inhibition or deficiency alleviated DOX-induced cardiotoxicity in vivo, as well as cardiac myocyte (CM) death and atrophy in vitro. In ovarian cancer cells, PDE10A inhibition induced cell death and reduced cell proliferation; as well as potentiated the effect of DOX on antagonizing cancer cells. Interestingly, in nude mice with ovarian cancer xenografts, PDE10A inhibition attenuated ovarian tumor growth while protected DOX-induced cardiotoxicity. RNAseq and bioinformatics analysis uncovered a number of PDE10A-regulated signaling pathways and cellular processes involved in DOX-induced cardiotoxicity. Mechanistic studies further revealed that PDE10A regulates CM death and atrophy via different mechanistic actions: regulating CM death via a cGMP-dependent while cAMP-independent mechanism; and regulating CM atrophy via a mechanism dependent on both cGMP and cAMP. Several PDE10A inhibitors have been tested in humans and successfully passed phase I clinical trials for safety. Thus, our findings suggest that PDE10A may be a safe "druggable" target for cancer therapy by simultaneously preventing DOX-induced cardiotoxicity and antagonizing tumor growth.

19.
Beilstein J Org Chem ; 17: 2425-2432, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34621404

RESUMO

The p-TsOH-catalyzed Diels-Alder reaction of 3-(indol-3-yl)maleimides with chalcone in toluene at 60 °C afforded two diastereoisomers of tetrahydropyrrolo[3,4-c]carbazoles, which can be dehydrogenated by DDQ oxidation in acetonitrile at room temperature to give the aromatized pyrrolo[3,4-c]carbazoles in high yields. On the other hand, the one-pot reaction of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones with chalcones or benzylideneacetone in acetonitrile in the presence of p-TsOH and DDQ resulted in polyfunctionalized carbazoles in satisfactory yields. The reaction mechanism included the DDQ oxidative dehydrogenation of 3-(indol-3-yl)-1,3-diphenylpropan-1-ones to the corresponding 3-vinylindoles, their acid-catalyzed Diels-Alder reaction and sequential aromatization process.

20.
J Cosmet Dermatol ; 20(12): 3829-3838, 2021 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-34599626

RESUMO

Acne is a common but chronic skin disease that influence large population especially juvenile. Acne can continue, begin, or grow into severe form in adult age, affecting face, back, and chest. It may be a serious issue if not cared or treated timely. Even if acne got treated it leaves a persistent scar, which is difficult to alleviate. These acne lesions are long-lasting and result in significant impact on mental and physical health of an individual. There are four mechanisms that are involved in acne lesion formation. However, the accurate series of events of the interaction among the factors in acne pathogenesis is still unsettled. Pubescent acne is due to increase hormone levels, when in fact adult acne is due to fluctuation in hormone levels. There are various approaches for the treatment of acne, including oral medications, creams or gels, acupuncture. Traditional Chinese Medicine stated acne as a infection that is associated with the pathogenic influence of damp heat and heat on specific meridians. As an ancient and integral part of Chinese medicine acupuncture therapy is employed in the treatment of many diseases including acne. It functions by ameliorating the deep-rooted mechanisms playing crucial role in acne development. In this review, we have explained the acne causes, pathogenesis, and its available treatment options. Additionally, we also discussed the acupuncture therapy methods, devices, different techniques. and its mechanism of action in treating acne. Furthermore, clinical trials studies motivated us to highlight the scope of acupuncture in the growing system of medicine.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...