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1.
ACS Omega ; 6(43): 28620-28629, 2021 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-34746557

RESUMO

The ultradeep carbonate reservoir in Sichuan Basin is characterized by deep burial depth, high temperature, and strong heterogeneity. In the early stage of production, the vertical well acid fracturing is the main reservoir stimulation method, and the horizontal well stimulation technology is not mature enough to release the production capacity of gas wells. Segmented acid fracturing of the ultradeep horizontal wells currently faces the following problems: the strong heterogeneity of reservoir leads to the difficulty of fine segmentation; the high reservoir temperature requires higher performance of working fluid; the reaction rate between acid and rock is fast and the action distance of acid is short, and there is low fracture conductivity under high closure stress. In view of the above problems, the fine segmented design method was studied, and the high-temperature-resistant authigenic acid and gelling acid systems were developed. The viscosity of authigenic acid is greater than 150 mPa s after shearing at 160 °C and 170 s-1 for 50 min, and the highest acid generation concentration is 4.05 mol/L. The gelling acid system has both the properties of high-temperature resistance and low friction resistance; not only canit meet the requirements of the retarding rate and the corrosion inhibition ability when the reservoir temperature is 160 °C but also the resistance reduction rate is up to more than 70%. By alternating injection of authigenic acid and gelling acid, the acid-etched fracture length and conductivity were, respectively, increased by 80% and 45%. The application of this technology in the horizontal well of the ultradeep carbonate reservoir in Sichuan Basin can increase the productivity by 3 times when compared with the vertical well acid fracturing, and a better stimulation effect has been achieved.

2.
Pest Manag Sci ; 2021 Nov 13.
Artigo em Inglês | MEDLINE | ID: mdl-34773351

RESUMO

BACKGROUND: Bactrocera dorsalis is a devastating pest on fruits and vegetables because the adult female is the key factor that determines the population density of offspring and the degree of host damage. Unfortunately, there is still a lack of effective female attractants for behavioral control. Males of B. dorsalis fed on methyl eugenol (ME) were shown to be more sexually attracted to females and, therefore, were more successful in mating over ME-deprived males. RESULTS: In the current study, we demonstrated that (E)-coniferyl alcohol (E-CF), one of the ME metabolites in males, was highly attractive to sexually-mature females in laboratory bioassays. During the dusk courtship period, mature females showed the highest response to E-CF. However, there were no significant differences in olfactory responses to E-CF between virgin and mated mature females. Moreover, no obvious signs and symptoms of toxicity or death were observed in mice during a 14-day acute oral toxicity test. Toxicologically, no significant changes were observed in body weight, water intake, food consumption and absolute and relative organ weights between control and treated groups of healthy-looking mice, implying that E-CF could be regarded as non-toxic. Furthermore, cytotoxicity assessment revealed that E-CF was non-toxic against human fetal lung fibroblast 1 (HFL1), human breast cancer (MDA-MB-231), mouse embryonic hepatocytes (BNL-CL.2) and Spodoptera frugiperda ovary (SF-9) cell lines. CONCLUSIONS: E-CF proved to be an effective, promising and eco-friendly lure to B. dorsalis females. Therefore, this study may facilitate the development of novel control strategies against B. dorsalis in the field.

3.
J Gastrointest Oncol ; 12(4): 1786-1796, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34532128

RESUMO

Background: Racial disparities in the survival of patients with hepatocellular carcinoma (HCC) exist. Gene mutations have a profound effect on carcinogenesis, are easily affected by environment and etiology factors, and may result in survival divergences among patients with different racial backgrounds. This report explores the effects of gene mutations on the survival of American Caucasians and Asian patients. Methods: The sequencing and clinical data of 336 HCC patients were obtained from The Cancer Genome Atlas (TCGA) database. The sequencing data was subject to gene mutation profiling, and an analysis of immune cell infiltration was conducted. A multivariate analysis was performed to assess the independent effects of gene mutations on patients' overall survival (OS) and disease-free survival (DFS). Results: Asian HCC patients had a significantly higher level of TP53 mutation frequency than Caucasian HCC patients (Asian vs. Caucasian, 39% vs. 23%; P=0.003). The TP53 mutation was associated with shorter OS [hazard ratio (HR), 2.33; 95% confidence interval (CI), 1.36-3.97; P=0.002] and DFS (HR, 2.2; 95% CI, 1.38-3.51; P<0.001) in Caucasian HCC patients, but had no effect on Asian HCC patients' survival. Compared to Asian HCC patients, Caucasian HCC patients with the TP53 mutation had a decreased proportion of infiltrating M2 macrophages and activating natural killer (NK) cells, and an increased proportion of follicular helper T cells. The RB1 mutation was associated with shorter OS (HR, 3.37; 95% CI, 1.73-6.57; P<0.001) in Asian HCC patients, and shorter DFS (HR, 2.11; 95% CI, 1.15-3.88; P=0.017) in Caucasian HCC patients. Asian HCC patients with the RB1 mutation had a decreased proportion of infiltrating CD8 T cells. Conclusions: The effects of the TP53 and RB1 mutations on survival differ among Asian and Caucasian HCC patients.

4.
Front Immunol ; 12: 712351, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34504494

RESUMO

Hepatocellular carcinoma (HCC) is an aggressive liver tumor that occurs due to chronic liver disease, and it has a high mortality rate and limited treatment options. Immune checkpoint inhibitors have been successfully introduced and used in cancer therapy, among which inhibitors of programmed death ligand-1 (PD-L1) and its receptor programmed death-1 (PD-1) are commonly administered for HCC as combination therapy, including combined anti-angiogenic and immunotherapy combination therapy. We report a case of a primary massive HCC patient with portal hepatic vein tumor thrombus who had a good response to atezolizumab in combination with bevacizumab, following progression of disease on combined immunotherapy with pembrolizumab and lenvatinib. This case demonstrates for the first time that an HCC patient who is resistant to anti-PD-1 antibody immunotherapy can benefit from anti-PD-L1 antibody immunotherapy, providing a potentially promising strategy for the treatment of HCC.

5.
Neuropsychiatr Dis Treat ; 17: 2647-2657, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34421300

RESUMO

Purpose: This study aimed to investigate the mechanism of working memory (WM) impairment in drug-naive obsessive-compulsive disorder (OCD) by using neuropsychological tests and proton magnetic resonance spectroscopy (1H-MRS). Patients and Methods: A total of 55 patients with drug-naive OCD and 55 healthy controls (HCs) were recruited for this study. The working memory (WM) was evaluated using the digit span test (DST), visual space memory test (VSMT), and the 2-back task and stroop color word test (SCWT). The bilateral metabolite levels of the prefrontal cortex (PFC) were evaluated by 1H-MRS, then determined the ratios of N-acetyl aspartate (NAA), choline-containing compounds (Cho), and myo-inositol (MI) to creatine (Cr). The independent sample t-test was used to analyse the differences in WM performance and neurometabolite ratios. Multivariate linear regression analysis was performed to screen the influential factors of WM, with an introduction level of 0.05 and a rejection level of 0.10. Results: 1) Patients with OCD performed significantly worse on DST (score), VSMT (score), 2-back task (accuracy rate), SCWT (execution time) when compared with HCs. 2) NAA/Cr and Cho/Cr in the left PFC (lPFC) and MI/Cr ratios in the bilateral PFC of OCD patients were significantly lower when compared to HCs. 3) For OCD patients, the NAA/Cr ratio in the lPFC was negatively correlated with the score of DST (forwards), the Cho/Cr ratio in the lPFC was positively correlated with the accuracy rate of 2-back task, and the MI/Cr ratio in the right PFC (rPFC) was positively correlated with the score of DST (forwards) and the accuracy rate of VSMT. We also found that the compulsive symptoms showed a positive correlation with MI/Cr ratio of the rPFC. Conclusion: Drug-naive OCD patients have demonstrated WM impairments, including phonological loop, visual-spatial sketchpad and central executive system, and the WM impairments might be associated with hypometabolism in the PFC, especially the lPFC.

6.
J Cancer ; 12(18): 5674-5680, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34405027

RESUMO

Objective: The present study aimed to explore the expressions of long noncoding RNA (lncRNA) p53 upregulated regulator of p53 levels (PURPL) in different ovarian tissues, and to evaluate the significance of disregulations of PURPL and microRNA-338-3p (miR-338-3p) in epithelial ovarian cancer (EOC). Methods: The expressions of PURPL in ovarian cancer, the relations between PURPL and the prognosis of ovarian cancer, and the relation between PURPL and miR-338-3p were queried in multiple biomedical databases. Real-time PCR was performed to detect the expressions of PURPL in different ovarian tissues. Logistic regression analysis was used to analyze the risk factors of recurrence and death. Kaplan-Meier analysis was implemented to evaluate the relations between PURPL and miR-338-3p expressions and the survival of ovarian cancer. Results: PURPL could target miR-338-3p, PURPL were upregulated in ovarian cancer tissues, upregulation of PURPL in ovarian cancer was negatively related with the recurrence free survival (RFS) and overall survival (OS), which were indicated by biomedical databases query. Our data showed upregulations of PURPL were noted in ovarian cancer tissues. Higher expressions of PURPL were associated with more advanced FIGO stage and developed lymph node metastasis in epithelial ovarian cancer. Upregulation of PURPL was related with the recurrence (P=0.002, OR=21.482, 95%CI: 3.457~94.251) and death (P=0.004, OR=35.643, 95%CI: 2.453~84.359) of ovarian cancer patient. PURPL expressions were negatively correlated to miR-338-3p expressions in different ovarian tissues (r = -0.968, P<0.0001). Poor RFS (χ2=19.410, P=0.0002) and OS (χ2=17.600, P=0.0005) were found in patients with high level PURPL and low level miR-338-3p expressions. Conclusions: Upregulation of PURPL and downregulation of miR-338-3p were related with the poor RFS and OS of ovarian cancer, which indicated disregulations of PURPL and miR-338-3p could serve as prognosis biomarkers for epithelial ovarian cancer.

7.
Sci Total Environ ; 794: 149576, 2021 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-34426016

RESUMO

Agricultural works alter earth's surface at the largest scale among human-driven activities. Previous studies have focused more on the reclamation of natural land, however, farmland marginalization (FM), emerging as an important mean of land use changes in mountainous and hilly areas (MHAs) has always been overlooked in the background of production efficiency improvement along with urbanization and population migration. This paper examined the characteristics of the spatial-temporal distribution and conversion of marginalized farmland in the MHAs of China at county level (excluding Hong Kong, Macau, and Taiwan) from 1990 to 2020, regarding farmland in MHAs converted into non-built-up land as FM. The results showed that: (1) The total area of marginalized farmland in the MHAs was 1.03 × 106 km2. The counties with larger area of marginalized farmland were concentrated around the Hu Line, and those with higher ratio were distributed in southern mountainous areas. (2) The area of marginalized farmland in each stage exhibited a fluctuating trend from 1990 to 2020. Forests and grasslands were prioritized as the desirable types in land conversion, and had prominent spatial agglomeration. (3) The influence of FM in MHAs on land use changes at county level demonstrated significant spatial-temporal heterogeneity, with wide range and low intensity from 1990 to 2000 and 2015 to 2020, and narrow range and high intensity from 2000 to 2015, and the counties with high intensity were distributed in the Loess Plateau and Sichuan-Chongqing hilly region. (4) The slope of marginalized farmland exhibited a prominent rule of spatial distribution, but an insignificant temporal trend under the influence of governmental policies. The larger the slope was, the higher the degree of marginalization was, but not necessarily earlier it occurred. The results can provide a reference for the formulation and implementation of farmland protection policies.


Assuntos
Agricultura , Florestas , China , Fazendas , Humanos , Urbanização
8.
J Exp Bot ; 2021 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-34397079

RESUMO

In soybean, heterosis achieved through the three-line system has been gradually applied in breeding to increase yield, but the underlying molecular mechanism remains unknown. We conducted a genetic analysis using the pollen fertility of offspring of the cross NJCMS1A×NJCMS1C. All F1 plants' pollen was semi-sterile; in F2, the ratio of pollen-fertile plants to pollen semi-sterile plants was 208:189. This result indicates NJCMS1A is gametophyte sterile, and the fertility restoration of NJCMS1C to NJCMS1A is a quality trait controlled by a single gene locus. Using bulked segregant analysis, the fertility restorer gene Rf in NJCMS1C was located on chromosome 16 between the markers BARCSOYSSR_16_1067 and BARCSOYSSR_16_1078. Sequence analysis of genes in that region showed that GmPPR576 was non-functional in rf cultivars. GmPPR576 has one functional allele in Rf cultivars but three non-functional alleles in rf cultivars. Phylogenetic analysis showed that the GmPPR576 locus evolved rapidly with the presence of male-sterile cytoplasm. GmPPR576 belongs to the RFL fertility restorer gene family and is mitochondrial-targeted. GmPPR576 was knocked out in soybean N8855 using CRISPR/Cas9. The T1 plants showed sterile pollen, and T2 plants produced few pods at maturity. The results indicate that GmPPR576 is the fertility restorer gene of NJCMS1A.

9.
J Genet Genomics ; 48(9): 851-859, 2021 09 20.
Artigo em Inglês | MEDLINE | ID: mdl-34411712

RESUMO

The dysbiosis of microbiome may have negative effects on a host phenotype. The microbes related to the host phenotype are regarded as microbial association signals. Recently, statistical methods based on microbiome-phenotype association tests have been extensively developed to detect these association signals. However, the currently available methods do not perform well to detect microbial association signals when dealing with diverse sparsity levels (i.e., sparse, low sparse, non-sparse). Actually, the real association patterns related to different host phenotypes are not unique. Here, we propose a powerful and adaptive microbiome-based association test to detect microbial association signals with diverse sparsity levels, designated as MiATDS. In particular, we define probability degree to measure the associations between microbes and the host phenotype and introduce the adaptive weighted sum of powered score tests by considering both probability degree and phylogenetic information. We design numerous simulation experiments for the task of detecting association signals with diverse sparsity levels to prove the performance of the method. We find that type I error rates can be well-controlled and MiATDS shows superior efficiency on the power. By applying to real data analysis, MiATDS displays reliable practicability too. The R package is available at https://github.com/XiaoyunHuang33/MiATDS.

10.
Front Immunol ; 12: 713294, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34349770

RESUMO

The development and differentiation of T cells represents a long and highly coordinated, yet flexible at some points, pathway, along which the sequential and dynamic expressions of different transcriptional factors play prominent roles at multiple steps. The large ZBTB family comprises a diverse group of transcriptional factors, and many of them have emerged as critical factors that regulate the lineage commitment, differentiation and effector function of hematopoietic-derived cells as well as a variety of other developmental events. Within the T-cell lineage, several ZBTB proteins, including ZBTB1, ZBTB17, ZBTB7B (THPOK) and BCL6 (ZBTB27), mainly regulate the development and/or differentiation of conventional CD4/CD8 αß+ T cells, whereas ZBTB16 (PLZF) is essential for the development and function of innate-like unconventional γδ+ T & invariant NKT cells. Given the critical role of T cells in host defenses against infections/tumors and in the pathogenesis of many inflammatory disorders, we herein summarize the roles of fourteen ZBTB family members in the development, differentiation and effector function of both conventional and unconventional T cells as well as the underlying molecular mechanisms.

11.
Adv Healthc Mater ; 10(20): e2100978, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34387391

RESUMO

Tumor reprogram pathway of mitochondrial metabolism is an emerging approach for malignant tumor treatment, such as triple-negative breast cancer. In this study, a tumor/mitochondria cascaded targeting, adenosine-triphosphate (ATP) responsive nanocarrier of zeolitic imidazolate framework-90 (ZIF-90) for breast cancer combination therapy is reported. Atovaquone (AVO) and hemin are loaded into ZIF-90, then a peptide iRGD with tumor-targeting ability is modified on the ZIF-90 nanoplatform. Hemin can specifically degrade BTB and CNC homology1 (BACH1), resulting in the changes of mitochondrial metabolism, and AVO acts as the inhibitor of the electron transport chain (ETC). The degradation of BACH1 using hemin can effectively improve the anti-tumor efficiency of mitochondrial metabolism inhibitor AVO, by increasing dependency on mitochondrial respiration. This nanoplatform displays both tumor-targeting and mitochondria-targeting capacity with high level of ATP responsive drug release behavior. The specific characteristic of mitochondria-targeting ability of this nanoplatform can increase the accumulation of AVO in the mitochondria, and in turn, can effectively improve the inhibition of the ETC. Both in vitro and in vivo results reveal that this composite nanocarrier has excellent tumor inhibition ability with limited side effects. Accordingly, this study provides an attractive strategy in the mitochondrial metabolism for cancer targeted therapy.


Assuntos
Neoplasias de Mama Triplo Negativas , Zeolitas , Trifosfato de Adenosina/metabolismo , Linhagem Celular Tumoral , Liberação Controlada de Fármacos , Humanos , Mitocôndrias/metabolismo , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismo
12.
J Neurosci ; 2021 Jun 04.
Artigo em Inglês | MEDLINE | ID: mdl-34099507

RESUMO

Maintaining and manipulating sequences online is essential for daily activities such as scheduling a day. In Parkinson's disease (PD), sequential working memory deficits have been associated with altered regional activation and functional connectivity in the basal ganglia. This study demonstrates that the substantia nigra (SN) integrity correlated with basal ganglia function and sequencing performance in 29 patients with PD (17 women) and 29 healthy controls (HC, 18 women). In neuromelanin-sensitive structural MRI, PD patients showed smaller SN than HC. In a digit ordering task with functional MRI, participants either recalled sequential digits in the original order ('pure recall') or rearranged the digits and recalled the new sequence ('reorder & recall'). PD patients performed less accurately than HC, accompanied by the caudate and pallidal hypo-activation, subthalamic hyper-activation, and weakened functional connectivity between the bilateral SN and all three basal ganglia regions. PD patients with larger SN tended to exhibit smaller ordering-related accuracy costs ('reorder & recall' versus 'pure recall'). This effect was fully mediated by the ordering-related caudate activation. Unlike HC, the ordering-related accuracy cost correlated with the ordering-related caudate activation but not subthalamic activation in PD. Moreover, the ordering-related caudate activation correlated with the SN area but not the daily dose of D2/3 receptor agonists. In PD, the daily dose of D2/3 receptor agonists correlated with the ordering-related subthalamic activation, which was not related to the accuracy cost. The findings suggest that damage to the SN may lead to sequential working memory deficits in PD, mediated by basal ganglia dysfunction.SIGNIFICANCELiu et al. demonstrate that damage to the substantia nigra (SN) correlates with basal ganglia dysfunction and poor sequencing performance in Parkinson's disease (PD). In neuromelanin-sensitive MRI, PD showed smaller SN than healthy controls. In a digit ordering task with functional MRI, PD's lower task accuracy was accompanied by the caudate and pallidal hypo-activation, subthalamic hyper-activation, and weakened functional connectivity between the SN and basal ganglia. PD with larger SN exhibited greater ordering-related caudate activation and lower ordering-related accuracy cost when sequencing digits. PD with more daily exposure to D2/3 receptor agonists exhibited greater ordering-related subthalamic activation, which did not reduce accuracy cost. It suggests that the SN may affect sequencing performance by regulating the task-dependent caudate activation in PD.

13.
Artigo em Inglês | MEDLINE | ID: mdl-34077368

RESUMO

Over the past decades, Chemical-induced Disease (CID) relations have attracted extensive attention in biomedical community, reflecting wide applications in biomedical research and healthcare field. However, prior efforts fail to make full use of the interaction between local and global contexts in biomedical document, and the derived performance needs to be improved accordingly. In this paper, we propose a novel framework for document-level CID relation extraction. More specifically, a stacked Hypergraph Aggregation Neural Network (HANN) layers are introduced to model the complicated interaction between local and global contexts, based on which better contextualized representations are obtained for CID relation extraction. In addition, the CID Relation Heterogeneous Graph is constructed to capture the information with different granularities and improve further the performance of CID relation classification. Experiments on a real-world dataset demonstrate the effectiveness of the proposed framework.

14.
Cancer Treat Res Commun ; 27: 100377, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33945921

RESUMO

Non-small cell lung cancer (NSCLC) patients with oncogenic ROS1 rearrangements would inevitably develop drug resistance and disease progression after receiving targeted oncogene therapy. Here, we present a metastatic lung adenocarcinoma patient harboring a CD74-ROS1 fusion who initially responded to crizotinib and then developed resistance after acquiring a rarely reported BRAF V600E mutation.

15.
J Mater Chem B ; 9(20): 4143-4153, 2021 05 26.
Artigo em Inglês | MEDLINE | ID: mdl-33973611

RESUMO

Synergistic therapies, such as chemo-photodynamic therapy, have been growing fast because of their efficacy against cancers. Although metal-organic frameworks have been widely studied in the field of drug delivery, the metal-organic frameworks (MOFs) with a two-dimensional (2D) structure integrated by photosensitizers are rarely reported. However, chemo-photodynamic therapy still has limitations such as the inhibitory effect from intracellular glutathione (GSH). In this work, a simple bottom-up synthesis method was used to synthesize a pH-responsive drug delivery system with a 2D MOF structure. In particular, tetracarboxyporphyrin (TCPP) derivatives were coordinated with bivalent copper ions as organic bridging molecules in a polyvinylpyrrolidone (PVP) solution, and copper porphyrin MOFs (Cu-TCPP nanosheets) were synthesized by a hydrothermal method from bottom to top. DOX was loaded onto Cu-TCPP nanosheets by π-π stacking with a high drug loading rate of 33%. DOX@Cu-TCPP nanosheets showed pH-responsive DOX releasing behaviour and significant GSH scavenging ability. In addition, the evaluation of in vitro and in vivo treatment showed that DOX@Cu-TCPP nanosheets had high anti-tumor activity and excellent biocompatibility. Therefore, this study opens a new idea for the application of MOF nanosheets in tumor therapy and provides a supporting basis for the treatment of cancers by chemo-photodynamic synergistic therapy.


Assuntos
Antibióticos Antineoplásicos/farmacologia , Doxorrubicina/farmacologia , Estruturas Metalorgânicas/farmacologia , Nanopartículas/química , Fotoquimioterapia , Animais , Antibióticos Antineoplásicos/química , Apoptose/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Ensaios de Seleção de Medicamentos Antitumorais , Feminino , Neoplasias Mamárias Experimentais/tratamento farmacológico , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Estruturas Metalorgânicas/química , Camundongos , Camundongos Endogâmicos BALB C , Camundongos Nus , Células Tumorais Cultivadas
16.
J Gene Med ; 23(7): e3340, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33835620

RESUMO

BACKGROUND: Ectopic thymic carcinoma (TC) is an extremely rare disease with a poor prognosis. The main treatment for early TC is surgery, although an effective treatment for advanced TC is lacking. METHODS: We present the case of a 61-year-old man with advanced posterior mediastinum thymic squamous cell carcinoma. Amplification refractory mutation system (ARMS)-polymerase chain reaction (PCR) analysis was used to investigate the molecular and mutational characteristics of this tumour. RESULTS: After chemotherapy and radiotherapy, the tumour showed disease progression. Immunohistochemistry revealed that the tumour was positive for CD117 (specific for primary TC), CK19, CD56 and Ki67. ARMS-PCR analysis revealed an EGFR exon 19 deletion in the patient. The patient subsequently received icotinib treatment and achieved complete remission for 3 years. CONCLUSIONS: This case report suggests that tyrosine kinase inhibitors are a potential treatment strategy for patients with TC harbouring EGFR alterations.

17.
Front Aging Neurosci ; 13: 636545, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33643026

RESUMO

Patients with Parkinson's disease (PD) were often observed with gastrointestinal symptoms, which preceded the onset of motor symptoms. Neuropathology of PD has also been found in the enteric nervous system (ENS). Many studies have reported significant PD-related alterations of gut microbiota. This meta-analysis was performed to evaluate the differences of gut microbiota between patients with PD and healthy controls (HCs) across different geographical regions. We conducted a systematic online search for case-control studies detecting gut microbiota in patients with PD and HCs. Mean difference (MD) and 95% confidence interval (CI) were calculated to access alterations in the abundance of certain microbiota families in PD. Fifteen case-control studies were included in this meta-analysis study. Our results showed significant lower abundance levels of Prevotellaceae (MD = -0.37, 95% CI = -0.62 to -0.11), Faecalibacterium (MD = -0.41, 95% CI: -0.57 to -0.24), and Lachnospiraceae (MD = -0.34, 95% CI = -0.59 to -0.09) in patients with PD compared to HCs. Significant higher abundance level of Bifidobacteriaceae (MD = 0.38, 95%; CI = 0.12 to 0.63), Ruminococcaceae (MD = 0.58, 95% CI = 0.07 to 1.10), Verrucomicrobiaceae (MD = 0.45, 95% CI = 0.21 to 0.69), and Christensenellaceae (MD = 0.20, 95% CI = 0.07 to 0.34) was also found in patients with PD. Thus, shared alterations of certain gut microbiota were detected in patients with PD across different geographical regions. These PD-related gut microbiota dysbiosis might lead to the impairment of short-chain fatty acids (SCFAs) producing process, lipid metabolism, immunoregulatory function, and intestinal permeability, which contribute to the pathogenesis of PD.

18.
Biol Pharm Bull ; 44(3): 396-403, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33642547

RESUMO

Ferulic acid (FA) has potential therapeutic effects in multiple diseases including cardiovascular diseases. However, the effect and molecular basis of FA in heart failure (HF) has not been thoroughly elucidated. Herein, we investigated the roles and mechanisms of FA in HF in isoproterenol (ISO)-induced HF rat model. Results found that FA ameliorated cardiac dysfunction, alleviated oxidative stress, reduced cell/myocardium injury-related enzyme plasma level, inhibited cardiocyte apoptosis in ISO-induced HF rat models. Moreover, FA reduced the co-localization of Keap1 and nuclear factor-E2-related factor 2 (Nrf2) in heart tissues of ISO-induced HF rats, and FA alleviated the inhibitory effects of ISO on expressions of p-Nrf2, heme oxygenase-1 (HO-1) and reduced nicotinamide adenine dinucleotide phosphate quinone dehydrogenase 1 (NQO1). Additionally, Nrf2 signaling pathway inhibitor ML385 showed adverse effects. FA weakened the effects of ML385 in ISO-induced HF rat models. Collectively, FA ameliorated HF by decreasing oxidative stress and inhibiting cardiocyte apoptosis via activating Nrf2 pathway in ISO-induced HF rats. Our data elucidated the underling molecular mechanism and provided a novel insight into the cardioprotective function of FA, thus suggested the therapeutic potential of FA in HF treatment.


Assuntos
Cardiotônicos/uso terapêutico , Ácidos Cumáricos/uso terapêutico , Insuficiência Cardíaca/tratamento farmacológico , Animais , Apoptose/efeitos dos fármacos , Cardiotônicos/farmacologia , Ácidos Cumáricos/farmacologia , Insuficiência Cardíaca/induzido quimicamente , Insuficiência Cardíaca/metabolismo , Insuficiência Cardíaca/fisiopatologia , Isoproterenol , Masculino , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Fator 2 Relacionado a NF-E2/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos
19.
Cell Commun Signal ; 19(1): 13, 2021 02 11.
Artigo em Inglês | MEDLINE | ID: mdl-33573688

RESUMO

BACKGROUND: Epimedii Folium (EF) is commonly used for treating bone fractures and joint diseases, but the potential hepatotoxicity of EF limits its clinical application. Our previous study confirms that EF could lead to idiosyncratic drug-induced liver injury (IDILI) and hepatocyte apoptosis, but the mechanism remains unknown. Studies have shown that NLRP3 inflammasome plays an important role in the development of various inflammatory diseases such as IDILI. Specific stimulus-induced NLRP3 inflammasome activation may has been a key strategy for lead to liver injury. Therefore, main compounds derived from EF were chosen to test whether the ingredients in EF could activate the NLRP3 inflammasome and to induce IDILI. METHODS: Bone-marrow-derived macrophages (BMDMs) were treated with Icariside I, and then stimulated with inflammasome stimuli and assayed for the production of caspase-1 and interleukin 1ß (IL-1ß) and the release of lactate dehydrogenase (LDH). Determination of intracellular potassium, ASC oligomerization as well as reactive oxygen species (ROS) production were used to evaluate the stimulative mechanism of Icariside I on inflammasome activation. Mouse models of NLRP3 diseases were used to test whether Icariside I has hepatocyte apoptosis effects and promoted NLRP3 inflammasome activation in vivo. RESULTS: Icariside I specifically enhances NLRP3 inflammasome activation triggered by ATP or nigericin but not SiO2, poly(I:C) or cytosolic LPS. Additionally, Icariside I does not alter the activation of NLRC4 and AIM2 inflammasomes. Mechanically, Icariside I alone does not induce mitochondrial reactive oxygen species (mtROS), which is one of the critical upstream events of NLRP3 inflammasome activation; however, Icariside I increases mtROS production induced by ATP or nigericin but not SiO2. Importantly, Icariside I leads to liver injury and NLRP3 inflammasome activation in an LPS-mediated susceptibility mouse model of IDILI, but the effect of Icariside I is absent in the LPS-mediated mouse model pretreated with MCC950, which is used to mimic knockdown of NLRP3 inflammasome activation. CONCLUSIONS: Our study reveals that Icariside I specifically facilitates ATP or nigericin-induced NLRP3 inflammasome activation and causes idiosyncratic hepatotoxicity. The findings suggest that Icariside I or EF should be avoided in patients with diseases related to ATP or nigericin-induced NLRP3 inflammasome activation, which may be risk factors for IDILI. Video abstract.

20.
Heart Fail Rev ; 26(4): 897-917, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-33544306

RESUMO

Although balloon pulmonary angioplasty (BPA) and pulmonary endarterectomy (PEA) are effective in chronic thromboembolic pulmonary hypertension (CTEPH), the comparison of their efficacy and safety is still unclear. We identified studies through a systematic review of PubMed, Cochrane Library, and Embase and used a random effects meta-analysis model to synthesize estimates of weighted mean differences or combined effect size. In total, 54 studies were included in this meta-analysis. The survival rates at perioperative/in-hospital period, 2 years, and 3 years were 100%, 99%, and 97%, respectively, in BPA group and 93%, 90%, and 88%, respectively, in PEA group. The variation of 6-min walk distance was 141.80 m in BPA and 100.73 m in PEA when the follow-up was 1-6 months. At < 1-month, 1-6-month, and > 12-month follow-up, the changed results of mean pulmonary arterial pressure were - 18.31, - 17.00, and - 12.97 mmHg in BPA group and - 18.93, - 21.21, and - 21.35 mmHg in PEA group. At < 1-month and 1-6-month follow-up, the changed values of pulmonary vascular resistance were - 542.24 and - 599.77 dyne•s•cm-5 in PEA group and - 443.49 and - 280.00 dyne•s•cm-5 in BPA group. In addition, there was more wide variety of complications in PEA group than in BPA group. BPA might have higher survival rate (perioperative/in-hospital period, 2-year and 3-year follow-up) and fewer types of complications compared with PEA. The improvement in exercise capacity (1-6-month follow-up) in the BPA group might be more pronounced than in PEA group. Moreover, PEA might be superior in improvement of hemodynamic parameters (< 1-month, 1-6-month, and > 12-month follow-up).

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