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1.
Sleep Med ; 96: 42-49, 2022 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-35594779

RESUMO

OBJECTIVE: Sleep disturbances have been linked with Parkinson's disease (PD) and amyotrophic lateral sclerosis (ALS) in observational studies, and the comorbidity of PD and ALS has been reported in clinical case reports, but the causalities remain unclear. This study aims to examine bidirectional causal relationships between sleep traits, PD and ALS. METHODS: Bidirectional two sample Mendelian randomisation (MR) analyses were conducted, with data from individuals of mainly European ancestry. Genetic instruments were obtained from the largest published genome-wide association studies (GWAS) concerning various sleep traits, PD and ALS. MR estimates from each genetic instrument were combined by inverse variance weighted method, with alternate methods (eg, weighted median, MR Egger, MR-PRESSO) and statistical graphs to assess horizontal pleiotropy and remove outliers. RESULTS: MR analysis failed to observe any causal association between sleep disorders and PD, but found a possible causal effect of PD risk on ALS risk (odds ratio [OR] = 1.07; 95% CI: 1.01-1.14, P < 0.01), albeit with a horizontal pleiotropy. Furthermore, MR analyses indicated that excessive daytime sleepiness (EDS) (OR = 2.29; 95% CI: 1.04-5.03, P = 0.04) contributed to a modest increase in risk of ALS, but the reverse causalities were not significant. Higher risk of ALS may be associated with being a "morning person" (OR = 1.03, P = 0.02), a longer sleep duration (OR = 1.01, P < 0.01), and a mean of 9 h or more total sleep duration (ß = 0.02, P = 0.04). CONCLUSIONS: Aided by large-scale GWAS, a shortage of evidence supporting causal relationships of sleep traits and PD risk, while significant evidence supports that EDS, higher PD risk may causally influence ALS risk. Future researches are required to explore the underlying pathological mechanism as well as the clinically significance, and replicate our findings using independent samples when data become available.

2.
Neuropsychiatr Dis Treat ; 18: 953-964, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35535211

RESUMO

Purpose: To evaluate the efficacy and safety of low dosages of rituximab (RTX) in the treatment of MuSK-antibody-positive MG patients. Patients and Methods: We retrospectively analyzed the data of MuSK-antibody-positive MG patients who were treated with low dosages of RTX from January 2018 to October 2021. The long-term treatment response to RTX was assessed by Myasthenia Gravis Foundation of America (MGFA) post-interventional status (PIS), Myasthenia Gravis Status and Treatment Intensity (MGSTI), dosage of steroid, MG-related activities of daily living (MG-ADL) and myasthenic muscle score (MMS) at the end of follow-up. Results: Clinical improvement was observed in all eight patients with follow-up for 8 to 29 months after treatment. At the last visit, complete stable remission had been achieved in one patient, pharmacologic remission in three patients, minimal manifestations status in three patients and improved in one patient based on the MGFA-PIS criteria. MGSTI level 2 or better had been reached in six (75%) patients at the last visit. The steroid dosage decreased from 60 mg at baseline to 15 mg at the last follow-up (p = 0.011). The average MG-ADL score decreased from 11 (range 7 to 15) to 0 (range 0 to 3; p = 0.011), and the MMS improved from 38.5 (range 24 to 60) to 100 (range 90 to 100; p = 0.012). These differences were all statistically significant. During RTX treatment and subsequent follow-up, 1 patient reported minor post-infusion malaise. Conclusion: Low-dose RTX is effective and safe for treating anti-MuSK antibody positive MG patients. A long-term response is observed after treatment. Larger prospective studies are required to provide further evidence.

3.
J Affect Disord ; 309: 266-273, 2022 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-35490875

RESUMO

OBJECTIVE: To investigate the impact of 10 common foods (including staple foods, fruits, vegetables, sugar, meat, fish, eggs, beans, salt-preserved vegetables, and garlic) on cognitive function in Chinese older adults. METHODS: Cross-sectional data on demographic characteristics, lifestyle, and dietary habits were taken from the 2018 Chinese Longitudinal Healthy Longevity Survey (CLHLS). Cognition was assessed using the Mini-Mental State Examination (MMSE). Food consumption was measured by participants reporting the frequency of their food consumption. Association between food groups and cognitive function was evaluated using mixed-effect regression model analysis. RESULTS: Compared with those who rarely or never consumed vegetables, meat, fruits, beans, and garlic, older adults who consumed these foods almost daily were 56%, 30%, 23%, 34%, and 29% less likely to have cognitive impairment, respectively. No associations between staple foods, sugar, fish, and eggs consumption and cognitive impairment were found. Low-frequency consumption of salt-preserved vegetables may be associated with cognitive function. Regular vegetables consumption had the greatest associated risk reduction of all food types. Interactions indicated that the co-ingestion of vegetables and beans or sugar, meat and beans may have antagonistic effect, while the co-ingestion of salt-preserved vegetables and garlic may have synergistic effect. Subgroup analyses showed that sex and age were the significant effect modifiers for meat and fish, respectively. CONCLUSIONS: Cognitive function of Chinese older adults may be related to food groups. Future research should measure food types and consumption level with greater granularity.


Assuntos
Disfunção Cognitiva , Idoso , China/epidemiologia , Disfunção Cognitiva/epidemiologia , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Estudos Transversais , Dieta , Comportamento Alimentar/psicologia , Humanos , Açúcares , Verduras
4.
Hum Resour Health ; 20(1): 42, 2022 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-35578232

RESUMO

BACKGROUND: General practitioners (GPs) were at risk of violence in their everyday working lives. Workplace violence (WPV) among GPs is a global public health concern. This study aimed to investigate the prevalence and factors associated with WPV among GPs in China. METHODS: A cross-sectional study was conducted among 4376 GPs in eastern, central, and western China between March and May 2021 using a structured self-administered questionnaire. The multivariable stepwise logistic regression model was used to examine the factors associated with WPV among GPs in China. RESULTS: Among these respondents, 14.26% of them reported exposure to WPV in the past 12 months. GPs who were female, practised in a rural area, made home visits occasionally, worked in a fair or good practice environment or work environment, and had a fair or good relationship with patients were less likely to encounter any type of WPV. In addition, GPs who served patients over 20 per day and worked overtime occasionally or frequently were more likely to be exposed to WPV. The determinants of WPV varied in different types of WPV and sexes. CONCLUSIONS: The prevalence of WPV among GPs is low in China. Our findings could inform the measures to reduce the WPV among GPs.

5.
Brain Sci ; 12(4)2022 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-35447979

RESUMO

This research measured human neural responses to images of different visual complexity levels using the oddball paradigm to explore the neurocognitive responses of complexity perception in visual processing. In the task, 24 participants (12 females) were required to react to images with high complexity for all stimuli. We hypothesized that high-complexity stimuli would induce early visual and attentional processing effects and may elicit the visual mismatch negativity responses and the emergence of error-related negativity. Our results showed that the amplitude of P1 and N1 were unaffected by complexity in the early visual processing. Under the target stimuli, both N2 and P3b components were reported, suggesting that the N2 component was sensitive to the complexity deviation, and the attentional processing related to complexity may be derived from the occipital zone according to the feature of the P3b component. In addition, compared with the low-complexity stimulus, the high-complexity stimulus aroused a larger amplitude of the visual mismatch negativity. The detected error negativity (Ne) component reflected the error detection of the participants' mismatch between visual complexity and psychological expectations.

6.
Integr Zool ; 2022 Apr 13.
Artigo em Inglês | MEDLINE | ID: mdl-35416418

RESUMO

Asymmetric competition occurs when some species have distinct advantages over their competitors and is common in animals with overlapping habitats and diet. However, the mechanism allowing coexistence between asymmetric competitors is not fully clear. Chinese white-bellied rats (Niviventer confucianus, CWR) and Korean field mice (Apodemus peninsulae, KFM) are common asymmetric competitors in shrublands and forests west of Beijing city. They share similar diet (e.g. plant seeds) and activity (nocturnal), but differ in body size (CWR are bigger than KFM), food hoarding habit (CWR: mainly larder hoarding; KFM: both larder and scatter hoarding), and ability to protect cached food (CWR are more aggressive than KFM). Here, we tested seed competition in 15 CWR-KFM pairs over a 10-day period under semi-natural enclosure conditions to uncover the differences in food hoarding, cache pilferage, and food protection between the 2 rodents, and discuss the implication for coexistence. Prior to pilferage, CWR harvested and ate more seeds than KFM. CWR tended to larder hoard seeds, whereas KFM preferred to scatter hoard seeds. Following pilferage, CWR increased consumption, decreased intensity of hoarding, and pilfered more caches from KFM than they lost, while KFM increased consumption more than they hoarded, and they preferred to hoard seeds in low and medium competition areas. Accordingly, both of the 2 rodent species increased their total energy consumption and hoarding following pilferage. Both rodent species tended to harvest seeds from the source, rather than pilfer caches from each other to compensate for cache loss via pilferage. Compared to CWR, KFM consumed fewer seeds when considering seed number, but hoarded more seeds when considering the seeds' relative energy (energy of hoarded seeds/rodent body mass2/3 ) at the end of the trials. These results suggest that asymmetric competition for food exists between CWR and KFM, but differentiation in hoarding behavior could help the subordinate species (i.e. KFM) hoard more energy than the dominant species (i.e. CWR), and may contribute to their coexistence in the field.

7.
Appl Environ Microbiol ; 88(8): e0162721, 2022 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-35369708

RESUMO

Saccharomyces cerevisiae is a well-performing workhorse in chemical production, which encounters complex environmental stresses during industrial processes. We constructed a multiple stress tolerance mutant, Med15V76R/R84K, that was obtained by engineering the KIX domain of Mediator tail subunit Med15. Med15V76R/R84K interacted with transcription factor Hap5 to improve ARV1 expression for sterol homeostasis for decreasing membrane fluidity and thereby enhancing acid tolerance. Med15V76R/R84K interacted with transcription factor Mga2 to improve GIT1 expression for phospholipid biosynthesis for increasing membrane integrity and thereby improving oxidative tolerance. Med15V76R/R84K interacted with transcription factor Aft1 to improve NFT1 expression for inorganic ion transport for reducing membrane permeability and thereby enhancing osmotic tolerance. Based on this Med15 mutation, Med15V76R/R84K, the engineered S. cerevisiae strain, showed a 28.1% increase in pyruvate production in a 1.0-L bioreactor compared to that of S. cerevisiae with its native Med15. These results indicated that Mediator engineering provides a potential alternative for improving multidimensional stress tolerance in S. cerevisiae. IMPORTANCE This study identified the role of the KIX domain of Mediator tail subunit Med15 in response to acetic acid, H2O2, and NaCl in S. cerevisiae. Engineered KIX domain by protein engineering, the mutant strain Med15V76R/R84K, increased multidimensional stress tolerance and pyruvate production compared with that of S. cerevisiae with its native Med15. The Med15V76R/R84K could increase membrane related genes expression possibly by enhancing interaction with transcription factor to improve membrane physiological functions under stress conditions.


Assuntos
Proteínas de Saccharomyces cerevisiae , Saccharomyces cerevisiae , Peróxido de Hidrogênio/metabolismo , Proteínas de Membrana/metabolismo , Piruvatos/metabolismo , Saccharomyces cerevisiae/genética , Saccharomyces cerevisiae/metabolismo , Proteínas de Saccharomyces cerevisiae/genética , Proteínas de Saccharomyces cerevisiae/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo
8.
Angew Chem Int Ed Engl ; : e202201321, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35415958

RESUMO

The vicinal oxygen chelate (VOC) metalloenzyme superfamily catalyzes a highly diverse set of reactions with the mechanism characterized by the bidentate coordination of vicinal oxygen atoms to metal ion centers, but there remains a lack of a platform to steer the reaction trajectories, especially for o-quinone metabolizing pathways. Herein, we present the directed-evolution-enabled bifunctional turnover of ChaP, which is a homotetramer and represents an unprecedented VOC enzyme class. Unlike the ChaP catalysis of extradiol-like o-quinone cleavage and concomitant α-keto acid decarboxylation, a group of ChaP variants (CVs) catalyze intradiol-like o-quinone deconstruction and CO2 liberation from the resulting o-hydroxybenzoic acid scaffolds with high regioselectivity. Enzyme crystal structures, labeling experiments and computational simulations corroborated that the D49L mutation allows the metal ion to change its coordination with the tyrosine phenoxy atoms in different monomers, thereby altering the reaction trajectory with the regiospecificity further improved by the follow-up replacement of the Y92 residue with any of alanine, glycine, threonine, and serine. The study highlights the unpredicted catalytic versatility and enzymatic plasticity of VOC enzymes with biotechnological significance.

9.
BMC Med ; 20(1): 120, 2022 Apr 12.
Artigo em Inglês | MEDLINE | ID: mdl-35410334

RESUMO

BACKGROUND: Organ-specific metastatic context has not been incorporated into the clinical practice of guiding programmed death-(ligand) 1 [PD-(L)1] blockade, due to a lack of understanding of its predictive versus prognostic value. We aim at delineating and then incorporating both the predictive and prognostic effects of the metastatic-organ landscape to dissect PD-(L)1 blockade efficacy in non-small cell lung cancer (NSCLC). METHODS: A total of 2062 NSCLC patients from a double-arm randomized trial (OAK), two immunotherapy trials (FIR, BIRCH), and a real-world cohort (NFyy) were included. The metastatic organs were stratified into two categories based on their treatment-dependent predictive significance versus treatment-independent prognosis. A metastasis-based scoring system (METscore) was developed and validated for guiding PD-(L)1 blockade in clinical trials and real-world practice. RESULTS: Patients harboring various organ-specific metastases presented significantly different responses to immunotherapy, and those with brain and adrenal gland metastases survived longer than others [overall survival (OS), p = 0.0105; progression-free survival (PFS), p = 0.0167]. In contrast, survival outcomes were similar in chemotherapy-treated patients regardless of metastatic sites (OS, p = 0.3742; PFS, p = 0.8242). Intriguingly, the immunotherapeutic predictive significance of the metastatic-organ landscape was specifically presented in PD-L1-positive populations (PD-L1 > 1%). Among them, a paradoxical coexistence of a favorable predictive effect coupled with an unfavorable prognostic effect was observed in metastases to adrenal glands, brain, and liver (category I organs), whereas metastases to bone, pleura, pleural effusion, and mediastinum yielded consistent unfavorable predictive and prognostic effects (category II organs). METscore was capable of integrating both predictive and prognostic effects of the entire landscape and dissected OS outcome of NSCLC patients received PD-(L)1 blockade (p < 0.0001) but not chemotherapy (p = 0.0805) in the OAK training cohort. Meanwhile, general performance of METscore was first validated in FIR (p = 0.0350) and BIRCH (p < 0.0001), and then in the real-world NFyy cohort (p = 0.0181). Notably, METscore was also applicable to patients received PD-(L)1 blockade as first-line treatment both in the clinical trials (OS, p = 0.0087; PFS, p = 0.0290) and in the real-world practice (OS, p = 0.0182; PFS, p = 0.0045). CONCLUSIONS: Organ-specific metastatic landscape served as a potential predictor of immunotherapy, and METscore might enable noninvasive forecast of PD-(L)1 blockade efficacy using baseline radiologic assessments in advanced NSCLC.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Antígeno B7-H1 , Ensaios Clínicos como Assunto , Humanos , Imunoterapia , Neoplasias Pulmonares/patologia , Intervalo Livre de Progressão
10.
J Healthc Eng ; 2022: 6368219, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35399851

RESUMO

Background: This study aimed to explore the clinical study of clopidogrel combined with Huoxue Tongluo prescription in improving transient ischemic attack (TIA) and the effect on MMP-9, Hcy, and CRP. Methods: A total of 84 patients with TIA admitted to our hospital from December 2019 to February 2021 were selected. The patients were divided into the control group (42 cases: not treated with Huoxue Tongluo prescription) and study group (42 cases: treatment with Huoxue Tongluo prescription). The clinical efficacy, adverse reactions, the levels of blood pressure and lipid, blood rheology and cerebral hemodynamics, neurological function-related indicators, MMP-9, Hcy, and CRP of the two groups were compared. Results: The total effective rate in the study group was higher than the control group. Compared with before treatment, the levels of SBP and DBP in both groups decreased memorably after treatment, and those in the study group decreased more particularly than the control group. The levels of LDL, HDL, TC, and TG in the study group were significantly better than those in the control group. The plasma viscosity, whole blood high shear viscosity, whole blood low shear viscosity, and hematocrit of patients in the study group were lower than those in the control group, and the maximum blood flow velocity, minimum blood flow velocity, average blood flow velocity, and average blood flow were higher than those in the control group. The levels of NSE, MBP, and S100ß in the study group were more memorably lower than those in the control group. After treatment, the levels of MMP-9, Hcy, and CRP in the study group were significantly lower than those in the control group. There was no obvious difference in the incidence of adverse reactions between the study group and control group. Conclusion: Clopidogrel combined with Huoxue Tongluo prescription can significantly improve the therapeutic effect and reduce the levels of MMP-9, Hcy, and CRP in patients with TIA.


Assuntos
Ataque Isquêmico Transitório , Clopidogrel/uso terapêutico , Medicamentos de Ervas Chinesas , Humanos , Ataque Isquêmico Transitório/tratamento farmacológico , Metaloproteinase 9 da Matriz , Prescrições
11.
J Med Chem ; 65(7): 5724-5750, 2022 04 14.
Artigo em Inglês | MEDLINE | ID: mdl-35357160

RESUMO

Endocrine therapies in the treatment of early and metastatic estrogen receptor α positive (ERα+) breast cancer (BC) are greatly limited by de novo and acquired resistance. Selective estrogen receptor degraders (SERDs) like fulvestrant provide new strategies for endocrine therapy combinations due to unique mechanisms. Herein, we disclose our structure-based optimization of LSZ102 by replacing 6-hydroxybenzothiophene with 6H-thieno[2,3-e]indazole. Subsequent acrylic acid degron modifications led us to identify compound 40 as the preferred candidate. In general, compound 40 showed much better pharmacological profiles than the lead LSZ102, exhibiting growth inhibition of wild-type or tamoxifen-resistant MCF-7 cells, potent ERα degradation, together with superior pharmacokinetic properties, directional target tissue distribution including the brain, and robust antitumor efficacy in the mice breast cancer xenograft model. Currently, 40 is being evaluated in preclinical trials.


Assuntos
Antineoplásicos , Neoplasias da Mama , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Neoplasias da Mama/patologia , Proliferação de Células , Resistencia a Medicamentos Antineoplásicos , Antagonistas de Estrogênios/farmacologia , Receptor alfa de Estrogênio/metabolismo , Feminino , Humanos , Indazóis/farmacologia , Indazóis/uso terapêutico , Células MCF-7 , Camundongos , Receptores de Estrogênio/metabolismo , Tiofenos
12.
Obes Rev ; 23(6): e13439, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-35293115

RESUMO

It is unclear whether maternal working time has an impact on offspring's weight-related outcomes especially obesity; the objective of this study is to conduct the first meta-analysis to focus on this topic. We searched PubMed, Ovid, and Web of Science databases through August 2021. A random-effect model was used to assess the pooled odds ratios (ORs) and regression coefficients (ß) with their corresponding 95% confidence intervals (95% CIs). Subgroup analyses were conducted to explore sources of heterogeneity. Publication bias was evaluated by the Egger's tests. Twenty-two observational studies were included with a total of 191,420 participants. Compared with children whose mothers worked less than 35 h/week, we found that children whose mothers worked more than 35 to 40 h/week had a 2.24-fold increased risk of childhood overweight/obesity (OR = 2.24, 95% CI: 1.61-3.11). An increment of 10 h/week in maternal working was associated with an approximately 1.0 percentage points in the probability of childhood overweight/obesity (ß = 0.008, 95% CI: 0.004-0.012). The pooled OR also indicated a similar result (OR = 1.09, 95% CI: 1.04-1.15). In addition, an increment of 10 h/week in maternal working was associated with 0.029 units increase in offspring's BMI z score (ß = 0.029, 95% CI: 0.016-0.042). Maternal long working hours is a potential risk factor for offspring's weight-related outcomes. Measures should be taken to protect the work welfare of females, thus facilitating the positive interaction of individual-family-society.


Assuntos
Mães , Obesidade Pediátrica , Índice de Massa Corporal , Criança , Feminino , Humanos , Sobrepeso , Obesidade Pediátrica/epidemiologia , Obesidade Pediátrica/etiologia , Fatores de Risco , Tempo
13.
Ann Transl Med ; 10(2): 84, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-35282076

RESUMO

Background: Transcatheter aortic valve implantation (TAVI) is an alternative method to treat patients with severe aortic valve disease. Accurate measurement of the aortic valve annulus and selection of the appropriate artificial valve are critical to the success of TAVI. Multilayer spiral computed tomography (MSCT) is recommended as the "gold standard" for assessing the aortic valve annulus before TAVI. However, MSCT scanning may not be possible for patients with iodine allergy, renal failure, or pregnancy. The purpose of this study is to evaluate the aortic valve annulus by three-dimensional transesophageal echocardiography (3D-TEE) and compare the results with MSCT, exploring the feasibility of 3D-TEE to guide the selection of artificial valve implantation in TAVI. Methods: We retrospectively analyzed 74 patients who successfully underwent TAVI in our hospital. Before the operation, 3D-TEE and MSCT were used to measure the maximum diameter, minimum diameter, area-derived diameter, and perimeter-derived diameter of the aortic valve annulus, and the results were analyzed for consistency. To predict the valve size based on 3D-TEE and the MSCT area-derived diameter, we compared the differences between the predicted valve size and the actual implanted valve size, and analyzed the differences between 3D-TEE and MSCT for guiding the selection of the prosthetic valve size. Results: There was no significant difference between 3D-TEE and MSCT in the measurement of the maximum diameter, minimum diameter, area, and perimeter of the aortic annulus and their derived diameter (P>0.05). The intraclass correlation coefficients for the maximum diameter, minimum diameter, area-derived diameter, and perimeter-derived diameter of the aortic annulus were 0.89, 0.83, 0.84, and 0.92, respectively. There was no statistical difference in the accuracy of both methods, 3D-TEE and MSCT, in predicting different prosthetic valve sizes for TAVI (P>0.05). Conclusions: 3D-TEE and MSCT have good agreement for measuring the values of various parameters of the aortic annulus. The accuracy of both methods was similar for predicting the aortic prosthetic valve size. 3D-TEE may provide guidance for selecting the prosthetic valve size for TAVI.

14.
Rare Metals ; : 1-24, 2022 Mar 11.
Artigo em Inglês | MEDLINE | ID: mdl-35291268

RESUMO

CO2-assisted oxidative dehydrogenation of propane (CO2-ODHP) is an attractive strategy to offset the demand gap of propylene due to its potentiality of reducing CO2 emissions, especially under the demands of peaking CO2 emissions and carbon neutrality. The introduction of CO2 as a soft oxidant into the reaction not only averts the over-oxidation of products, but also maintains the high oxidation state of the redox-active sites. Furthermore, the presence of CO2 increases the conversion of propane by coupling the dehydrogenation of propane (DHP) with the reverse water gas reaction (RWGS) and inhibits the coking formation to prolong the lifetime of catalysts via the reverse Boudouard reaction. An effective catalyst should selectively activate the C-H bond but suppress the C-C cleavage. However, to prepare such a catalyst remains challenging. Chromium-based catalysts are always applied in industrial application of DHP; however, their toxic properties are harmful to the environment. In this aspect, exploring environment-friendly and sustainable catalytic systems with Cr-free is an important issue. In this review, we outline the development of the CO2-ODHP especially in the last ten years, including the structural information, catalytic performances, and mechanisms of chromium-free metal-based catalyst systems, and the role of CO2 in the reaction. We also present perspectives for future progress in the CO2-ODHP.

15.
Artigo em Inglês | MEDLINE | ID: mdl-35341140

RESUMO

Aims: The study aims to explore the effects of the single-nucleotide polymorphism of miR-27a and its expression in Helicobacter pylori (H. pylori)-related diseases and the relationship between gastric pathology and traditional Chinese medicine (TCM). Methods: Subjects were classified into six histopathological groups and five TCM syndrome groups. All specimens underwent H. pylori detection through rapid urease test and methylene blue staining. Histopathological characteristics were observed by hematoxylin-eosin. The expression of miR-27a and its genotype were, respectively, detected by Quantitative Real-Time PCR and direct sequencing. Results: H. pylori promoted the malignant evolution of gastric mucosa and were involved in the formation of TCM syndrome. In H. pylori-positive patients, the frequency of miR-27a CT genotype at the rs895819 locus and its expression in the gastric cancer group were higher than those in other pathological groups. TCM syndrome had a close relationship with histopathological changes, and patients with spleen-qi deficiency syndrome had a higher risk of gastric cancer than other syndromes, regardless of H. pylori infection. Conclusion: The C allele at miR-27a rs895819 locus may be an oncogene in gastric cancer. High levels of miR-27a could play an important role in gastric malignant evolution, especially cancerization. There is a certain connection between TCM syndrome and pathological changes of the gastric mucosa to some extent, where patients with SQD syndrome had a higher risk of GC.

16.
Sheng Li Xue Bao ; 74(1): 110-116, 2022 Feb 25.
Artigo em Chinês | MEDLINE | ID: mdl-35199131

RESUMO

Hypertension is one of the strongest risk factors for cardiovascular diseases, cerebral stroke, and kidney failure. Lifestyle and nutrition are important factors that modulate blood pressure. Hypertension can be controlled by increasing physical activity, decreasing alcohol and sodium intake, and stopping tobacco smoking. Chronic kidney disease patients often have increased blood pressure, which indicates that kidney is one of the major organs responsible for blood pressure homeostasis. The decrease of renal sodium reabsorption and increase of diuresis induced by high potassium intake is critical for the blood pressure reduction. The beneficial effect of a high potassium diet on hypertension could be explained by decreased salt reabsorption by sodium-chloride cotransporter (NCC) in the distal convoluted tubule (DCT). In DCT cells, NCC activity is controlled by with-no-lysine kinases (WNKs) and its down-stream target kinases, Ste20-related proline-alanine-rich kinase (SPAK) and oxidative stress-responsive 1 (OSR1). The kinase activity of WNKs is inhibited by intracellular chloride ([Cl-]i) and WNK4 is known to be the major WNK positively regulating NCC. Based on our previous studies, high potassium intake reduces the basolateral potassium conductance, decreases the negativity of DCT basolateral membrane (depolarization), and increases [Cl-]i. High [Cl-]i inhibits WNK4-SPAK/OSR1 pathway, and thereby decreases NCC phosphorylation. In this review, we discuss the role of DCT in the blood pressure regulation by dietary potassium intake, which is the mechanism that has been best dissected so far.


Assuntos
Túbulos Renais Distais , Pressão Sanguínea , Dieta , Humanos , Rim/metabolismo , Túbulos Renais Distais/metabolismo , Fosforilação , Potássio/metabolismo , Potássio/farmacologia , Membro 3 da Família 12 de Carreador de Soluto/metabolismo
17.
Hepatology ; 2022 Jan 31.
Artigo em Inglês | MEDLINE | ID: mdl-35102596

RESUMO

BACKGROUND AND AIMS: NASH is associated with high levels of cholesterol and triglyceride (TG) in the liver; however, there is still no approved pharmacological therapy. Synthesis of cholesterol and TG is controlled by sterol regulatory element-binding protein (SREBP), which is found to be abnormally activated in NASH patients. We aim to discover small molecules for treating NASH by inhibiting the SREBP pathway. APPROACH AND RESULTS: Here, we identify a potent SREBP inhibitor, 25-hydroxylanosterol (25-HL). 25-HL binds to insulin-induced gene (INSIG) proteins, stimulates the interaction between INSIG and SCAP, and retains them in the endoplasmic reticulum, thereby suppressing SREBP activation and inhibiting lipogenesis. In NASH mouse models, 25-HL lowers levels of cholesterol and TG in serum and the liver, enhances energy expenditure to prevent obesity, and improves insulin sensitivity. 25-HL dramatically ameliorates hepatic steatosis, inflammation, ballooning, and fibrosis through down-regulating the expression of lipogenic genes. Furthermore, 25-HL exhibits both prophylactic and therapeutic efficacies of alleviating NASH and atherosclerosis in amylin liver NASH model diet-treated Ldlr-/- mice, and reduces the formation of cholesterol crystals and associated crown-like structures of Kupffer cells. Notably, 25-HL lowers lipid contents in serum and the liver to a greater extent than lovastatin or obeticholic acid. 25-HL shows a good safety and pharmacokinetics profile. CONCLUSIONS: This study provides the proof of concept that inhibiting SREBP activation by targeting INSIG to lower lipids could be a promising strategy for treating NASH. It suggests the translational potential of 25-HL in human NASH and demonstrates the critical role of SREBP-controlled lipogenesis in the progression of NASH by pharmacological inhibition.

18.
Nurs Open ; 9(3): 1757-1765, 2022 May.
Artigo em Inglês | MEDLINE | ID: mdl-35224873

RESUMO

AIM: To develop a self-management scale and evaluate its validity for pregnant woman with GDM in China. DESIGN: A cross-sectional survey design. METHODS: This study was conducted through three phases. The item pools of the scale were developed through literature review and expert interview. Content validity was assessed by an expert panel. Structure validity was evaluated through exploratory factor analysis. In the end, internal consistency reliability was tested. RESULTS: The self-management scale includes four dimensions, including self-management consciousness, pregnancy management, blood glucose management and resource utilization, with a total of 35 items. In the scale, the Cronbach's α was 0.95. The split-half reliability of the overall scale is 0.79. And the test-retest reliability was 0.91. The content validity was 0.94. CONCLUSIONS: The scale is significantly valid and reliable, and it can be used to evaluate the self-management ability of pregnant woman with GDM in China.


Assuntos
Diabetes Gestacional , Autogestão , Estudos Transversais , Diabetes Gestacional/diagnóstico , Diabetes Gestacional/terapia , Feminino , Humanos , Gravidez , Gestantes , Psicometria , Reprodutibilidade dos Testes , Inquéritos e Questionários
19.
Artigo em Inglês | MEDLINE | ID: mdl-35112252

RESUMO

Renal cell carcinoma (RCC) is a highly recurrent aggressive tumor. This study works for the regulation of miR-21-5p on RCC cell functions and novel ideas for therapies of RCC. Isoform expression quantification data were offered by The Cancer Genome Atlas Kidney Renal Clear Cell Carcinoma (TCGA-KIRC) to investigate differentially expressed miRNAs. The way miR-21-5p works on biological functions of RCC was examined with MTT and Transwell assays. The downstream targets of miR-21-5p were predicted using bioinformatics analysis. The binding of two researched objects was verified by the dual-luciferase method. TCGA data manifested a considerably high level of miR-21-5p in RCC tissue, while ARHGAP24 was significantly lowly expressed. miR-21-5p bound ARHGAP24 and stimulated RCC cell functions, whereas ARHGAP24 mimic could reverse such promotion. This work observed miR-21-5p, a stimulator in RCC, and it deteriorated this cancer via repressing its downstream target gene ARHGAP24 expression.

20.
Cell Death Discov ; 8(1): 84, 2022 Feb 26.
Artigo em Inglês | MEDLINE | ID: mdl-35217648

RESUMO

Breast cancer is one of the leading causes of mortality among women. Triple-negative breast cancer (TNBC) is responsible for a large percentage of all breast cancer deaths in women. This study demonstrated the function of Myb-like, SWIRM, and MPN domains 1 (MYSM1), an H2A deubiquitinase (DUB), in TNBC. MYSM1 expression was drastically decreased in breast cancer, especially in TNBC, suggesting a potential anticancer effect. Overexpressing and suppressing MYSM1 expression in TNBC cell lines led to significant biological changes in cell proliferation. Furthermore, MYSM1 overexpression increased cisplatin-induced apoptosis, which might be attributed to RSK3 inactivation and the subsequently decreased phosphorylation of Bcl-2 antagonist of cell death (BAD) (Ser 112). The findings suggest that MYSM1 is a potential target for regulating cell apoptosis and suppressing resistance to cisplatin in TNBC.

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