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1.
Int J Mol Sci ; 21(9)2020 Apr 26.
Artigo em Inglês | MEDLINE | ID: mdl-32357554

RESUMO

As non-viral transgenic vectors, the piggyBac transposon system represents an attractive tool for gene delivery to achieve a long-term gene expression in immunotherapy applications due to its large cargo capacity, its lack of a trace of transposon and of genotoxic potential, and its highly engineered structure. However, further improvements in transpose activity are required for industrialization and clinical applications. Herein, we established a one-plasmid effective screening system and a two-step high-throughput screening process in yeast to isolate hyperactive mutants for mammalian cell applications. By applying this screening system, 15 hyperactive piggyBac transposases that exhibited higher transpose activity compared with optimized hyPBase in yeast and four mutants that showed higher transpose activity in mammalian cells were selected among 3000 hyPBase mutants. The most hyperactive transposase, bz-hyPBase, with four mutation sites showed an ability to yield high-efficiency editing in Chinese hamster ovarian carcinoma (CHO) cells and T cells, indicating that they could be expanded for gene therapy approaches. Finally, we tested the potential of this screening system in other versions of piggyBac transposase.

2.
J Ethnopharmacol ; : 112915, 2020 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-32360044

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The genus Stellera comprises species of perennial herbs and shrubs, mainly distributed in the temperate regions of east Asia to west Asia. There are 10-12 species in the world, two species in China: S. chamaejasme and S. formosana Hayata. As recorded, the roots of Stellera species are used to dissipate phlegm and relieve pain. The roots and the barks can be used for papermaking. AIM OF THIS REVIEW: This review aims to summarize the ethnopharmacological uses, chemical constituents, pharmacological activities, clinical applications and toxicology of the genus Stellera to better understand their therapeutic potential in the future. MATERIALS AND METHODS: The relevant information of the genus Stellera was collected from scientific databases (Pubmed, ACS website, SciFinder Scholar, Elsevier, Google Scholar, Web of Science and CNKI). Information was also gathered from 'Flora Republicae Populairs Sinicae (《》)', folk records, conference papers on ethnopharmacology, Ph.D. and Masters' Dissertation. RESULTS: Stellera plants have been studied as traditional folk medicines all around the world. The chemical constituents of Stellera species mainly comprise terpenoids, flavonoids, coumarins, lignans, and so on. Extracts and compounds of Stellera species exhibit extensive pharmacological activities, such as anti-tumor, anti-convulsive, anti-epileptic, anti-bacterial, anti-viral and insecticidal, etc. Clinical applications have suggested that the genus Stellera has the effects in treating several skin diseases and cancers, however, the results should be further verification. The genus Stellera plants are toxic and should be used reasonable. CONCLUSION: This paper reviewed the ethnopharmacological use, chemical constituents, pharmacology, clinical applications and toxicology of the genus Stellera. The genus Stellera has broad application prospects. However, further in-depth studies are needed to determine the medical uses of the genus and its chemical constituents, pharmacological activities, clinical applications and toxicology.

3.
Inorg Chem ; 2020 May 04.
Artigo em Inglês | MEDLINE | ID: mdl-32364708

RESUMO

X-type hexaferrites have been receiving considerable attention due to their promising applications in many magnetic-electronic fields. However, the growth of single-crystal X-type hexaferrite is still a challenge. Herein we reported, for the first time, the preparation of single crystal X-type hexaferrite Sr2Co2Fe28O46 (Sr2Co2X) with high-quality and large size using floating-zone method with laser as the heating source. The crystals show rhombohedral symmetry with space group of R-3m (No. 166, a = 5.8935(1) Å and c = 83.7438(17) Å). Co2+ and Fe3+ oxidation states were confirmed by the X-ray absorption near-edge spectroscopy. The prepared Sr2Co2X exhibits a spin reorientation transition from easy-cone to easy-axis at T2 of 343 K and a ferrimagnetism-paramagnetism transition at Curie temperature (TC) of ∼743 K. The spin reorientation transition was accompanied by magnetocaloric effect (MCE). Both conventional and inverse MCEs were observed near T2 with a magnetic field applied along the c-axis. The maximum value of the magnetic entropy change along the c-axis was evaluated to be 1.1 J/kg·K for a magnetic field change of 5 T.

4.
J Exp Clin Cancer Res ; 39(1): 79, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381034

RESUMO

BACKGROUND: The poor prognosis of patients with ovarian cancer is mainly due to cancer progression. γ-Synuclein (SNCG) has reported as a critical player in cancer metastasis. However, its biological roles and mechanism are yet incompletely understood in ovarian cancer, especially in high-grade serous ovarian cancer (HGSOC). METHODS: This is a retrospective study of 312 patients with ovarian cancer at a single center between 2006 and 2016. Ovarian cancer tissues were stained by immunohistochemistry to analyze the relationship between SNCG expression and clinicopathologic factors. The clinical outcomes versus SNCG expression level were evaluated by Kaplan-Meier method and multiple Cox regression analysis. Next, systematical functional experiments were given to examine the proliferation and metastatic abilities of SNCG both in vitro and in vivo using loss- and gain- of function approaches. Furthermore, the mechanisms of SNCG overexpression were examined by human phospho-kinase array kit and western blot analysis. RESULTS: Clinically, the expression of SNCG was significantly upregulated in ovarian cancer compared with the borderline and benign tumor, normal ovary, and fallopian tube. Notably, the high level of SNCG correlated with high-risk clinicopathologic features and showed poor survival for patients with HGSOC, indicating an independent prognostic factor for these patients. Functionally, we observed that overexpression of SNCG promoted cell proliferation, tumor formation, migration, and invasion both in vitro and in vivo. Mechanistically, we identified that SNCG promoted cancer cell metastasis through activating the PI3K/AKT signaling pathway. CONCLUSIONS: Our results reveal SNCG up-regulation contributes to the poor clinical outcome of patients with HGSOC and highlight the metastasis-promoting function of SNCG via activating the PI3K/Akt signaling pathway in HGSOC.

5.
Infect Dis Poverty ; 9(1): 47, 2020 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-32381058

RESUMO

BACKGROUND: The incidence of brucellosis, which is caused by the Brucella species of bacteria, is rapidly rising worldwide; however, few studies have investigated the immune response to this pathogen and clinical biochemical features. In this paper, we examined the levels of various cytokines and inflammatory factors as well as clinical course characteristics in patients with brucellosis, in order to provide evidence for the diagnosis, assessment, and prognosis of this infectious disease. METHODS: A total of 191 brucellosis inpatients (50 acute cases and 141 chronic cases), as well as 60 healthy control subjects, were included in the analysis. We investigated changes in the levels of six cytokines (IL-4, IL-6, IL-10, IL-17, TNF-α, INF-γ) and related clinical biochemical markers in patients with acute and chronic brucellosis in Xinjiang, China. Possible factors were statistically analyzed using the t test, χ2 test, z test and a multivariate logistic stepwise regression test. RESULTS: We found that IL-4, IL-6, IL-10, IL-17, IFN-γ, and TNF-α levels were higher in those with brucellosis than in controls (P <  0.05). With regard to disease progression, procalcitonin (PCT) and C-reactive protein (CRP) levels were significantly higher in those with an acute infection compared to chronic cases (P <  0.05). We found that the expression of all six cytokines tested was closely related to the degree of brucellosis using univariate logistic regression; however, only IL-6 and INF-γ levels were independent factors associated with the severity of brucellosis. CONCLUSIONS: Assessing cytokine levels in patients with acute and chronic brucellosis is not only useful for detecting the immune response, but can also be indicative of the severity of brucellosis. In particular, we propose IL-6 and INF-γ levels may be useful independent predictive factors in the clinical evaluation and diagnosis of brucellosis.

6.
Front Immunol ; 11: 577, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32391001

RESUMO

Although the milestone discovery of immune checkpoint blockade (ICB) has been translated into clinical practice, only a fraction of patients can benefit from it with durable responses and subsequent long-term survival. Here, we tested the anti-tumor effect of combining PD-L1 blockade with 4-1BB costimulation in 3LL and 4T1.2 murine tumor models. Dual treatment induced further tumor regression and enhanced survival in tumor-bearing mice more so than PD-L1 and 4-1BB mAb alone. It was demonstrated that dual anti-PD-L1/anti-4-1BB immunotherapy increased the number of intratumoral CD103+CD8+ T cells and altered their distribution. Phenotypically, CD103+CD8+ T cells expressed a higher level of 4-1BB and PD-1 than their CD103- counterparts. Administration of PD-L1 mAb and 4-1BB mAb further increased the cytolytic capacity of CD103+CD8+ T cells. In vivo, CD103-CD8+ T cells could differentiate into CD103+CD8+ progeny cells. In a human setting, more CD8+ T cells differentiated into CD103+CD8+ T cells in the peripheral tumor region of lung cancer tissues than in the central tumor region. Collectively, infiltrated CD103+CD8+ T cells served as a potential effector T cell population. Combining 4-1BB agonism with PD-L1 blockade could increase tumor-infiltrated CD103+CD8+T cells, thereby facilitating tumor regression.

8.
Am J Chin Med ; : 1-19, 2020 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-32420752

RESUMO

Acupuncture reduces pain by activating specific areas called acupoints on the patient's body. When these acupoints are fully activated, sensations of soreness, numbness, fullness, or heaviness called De qi or Te qi are felt by clinicians and patients. There are two kinds of acupuncture, manual acupuncture and electroacupuncture (EA). Compared with non-acupoints, acupoints are easily activated on the basis of their special composition of blood vessels, mast cells, and nerve fibers that mediate the acupuncture signals. In the spinal cord, EA can inhibit glial cell activation by down-regulating the chemokine CX3CL1 and increasing the anti-inflammatory cytokine interleukin-10. This inhibits P38 mitogen-activated protein kinase and extracellular signal-regulated kinase pathways, which are associated with microglial activation of the C-Jun N-terminal kinase signaling pathway and subsequent astrocyte activation. The inactivation of spinal microglia and astrocytes mediates the immediate and long-term analgesic effects of EA, respectively. A variety of pain-related substances released by glial cells such as the proinflammatory cytokines tumor necrosis factor α, interleukin-1ß, interleukin-6, and prostaglandins such as prostaglandins E2 can also be reduced. The descending pain modulation system in the brain, including the anterior cingulated cortex, the periaqueductal gray, and the rostral ventromedial medulla, plays an important role in EA analgesia. Multiple transmitters and modulators, including endogenous opioids, cholecystokinin octapeptide, 5-hydroxytryptamine, glutamate, noradrenalin, dopamine, γ-aminobutyric acid, acetylcholine, and orexin A, are involved in acupuncture analgesia. Finally, the "Acupuncture +" strategy is introduced to help clinicians achieve better analgesic effects, and a newly reported acupuncture method called acupoint catgut embedding, which injects sutures made of absorbable materials at acupoints to achieve long-term effects, is discussed.

9.
Artigo em Inglês | MEDLINE | ID: mdl-32412799

RESUMO

Aims: The present study was designed to survey the associations between polymorphisms of the common single nucleotide polymorphism (SNP) rs4938723 in miR-34b/c gene, as well as the rs3746444 SNP in the miR-499 gene and impairment of spermatogenesis leading to oligospermia and azoospermia in the Chinese population. Subjects and Methods: Specimens were collected from four hundred seventeen infertile men with oligospermia or azoospermia and 234 controls for this investigation. Polymerase chain reaction and restriction fragment length polymorphism analyses was used for genotyping the rs4938723 and rs3746444 SNPs. A chi-square analysis was used to compare the differences in allelic and genotypic frequencies between patients and controls. Results: The distribution of alleles at the rs3746444 locus of the miR-499 gene in patients was not significantly different from incontrols. There were, however, significant differences in the genotypic (p = 0.040) and allelic (p = 0.021) distributions of rs4938723 SNPs between patients with oligospermia and controls. The CC genotypic at the rs4938723 locus was significantly higher in in patients with oligospermia than controls (13.9% vs. 7.3%, p = 0.016, odds ratio = 2.064, 95% confidence interval 1.132-3.764). Conclusion: The CC genotype of the rs4938723 locus in miR-34b/c gene may enhance susceptibility to oligospermia.

10.
Ann Palliat Med ; 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32434348

RESUMO

BACKGROUND: Obstructive sleep apnea-hypopnea syndrome (OSAHS) is recognized as an independent risk factor of cardiovascular disease. The release of Ca2+ mediated by transient receptor potential canonical (TRPC) channels participates in the hypoxia-induced pathophysiological changes in the cardiovascular systems in case of OSAHS. This study aimed to investigate which subtypes of TRPCs were involved in OSAHS in a rat model of intermittent hypoxia. METHODS: OSAHS was induced by exposure of rats to intermittent hypoxia. The expression of TRPCrelated genes and proteins in the cardiomyocytes by qRT-PCR and Western Blotting, respectively. RESULTS: The mRNA expression of TRPC3/TRPC4/TRPC5 increased significantly in OSAHS group compared with the control group (P<0.05). The TRPC5 protein expression was significantly higher in the OSAHS control than the control group (P<0.05). CONCLUSIONS: The TRPC5 channel is likely to be involved in the OSAHS induced pathophysiological changes in the myocardium and may become a target to prevent OSAHS related cardiac damage.

11.
Prenat Diagn ; 2020 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-32436246

RESUMO

OBJECTIVE: We aimed to investigate the value of whole-exome sequencing (WES) in fetuses with congenital anomalies of the kidney and urinary tract (CAKUT) with/without other structural anomalies but with normal findings upon karyotyping and chromosome microarray analysis (CMA). METHODS: Cases with CAKUT with/without other structural anomalies were screened for eligibility. Fetuses with abnormal karyotyping or CMA results were excluded. We performed WES on DNA samples from eligible fetus-parental trios and identified diagnostic genetic variants based on ultrasonographic features. RESULTS: A total of 163 eligible fetus-parental trios were successfully analyzed by WES. We found 26 likely pathogenic or pathogenic variants in 18 genes from 20 fetuses, with a total proportion of diagnostic genetic variants of 12.3% (20/163). Genetic variants were significantly more frequently detected in fetuses with multisystem anomalies (27.0%, 10/37), enlarged kidney/echogenic kidney (20%, 4/20) and multicystic dysplastic kidney (11.1%, 4/36). Pregnancy outcome data showed that 88 (94.6%, 88/93) of the surviving cases with negative WES results had a good prognosis in early childhood. CONCLUSIONS: Our study is the largest to use WES prenatally for CAKUT and shows that WES can be used diagnostically to define the molecular defects that underlie unexplained CAKUT.

12.
Int Immunopharmacol ; 84: 106570, 2020 May 12.
Artigo em Inglês | MEDLINE | ID: mdl-32413739

RESUMO

Cinnamaldehyde (CA) is an essential component of cinnamon (Cinnamomum cassia Presland), which is often used as a flavoring condiment in beverages, pastries, perfumes, etc. Cinnamon is also used as herbal medicine in China and Southeast Asia to treat rheumatoid arthritis. However, the molecular mechanism is unclear. In this study, we aim to investigate its anti-inflammatory effects against Rheumatoid arthritis (RA) using activated macrophages (Raw246.7) in vitro and adjuvant arthritis rats (AA) in vivo. The results demonstrated that CA significantly reduced synovial inflammation in AA rats, possibly due to suppression of the expressions of pro-inflammatory cytokines, especially the IL-1ß. Further investigation found that CA also suppressed the activity of HIF-1α by inhibiting the accumulation of succinate in cytoplasm. As we know, the reduction of HIF-1α nucleation slows down IL-1ß production, because HIF-1α activates the expression of NLRP3, which is involved in the assembly of inflammasome and processing of IL-1ß. In addition, CA also inhibited the expression of the succinate receptor GPR91, which in turn inhibited the activation of HIF-1α. In conclusions, our results suggested that CA might be a potential therapeutic compound to relieve rheumatoid arthritis progress by suppressing IL-1ß through modulating succinate/HIF-1α axis and inhibition of NLRP3.

13.
Int J Oncol ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32467999

RESUMO

Salivary adenoid cystic carcinoma (SACC) exhibits slow continuous growth, frequent local recurrences and a high incidence of blood metastasis, with advanced lung metastasis frequently occurring and being among the primary causes of mortality. MicroRNAs (miR) serve a significant role in the initiation and development of cancer and may be tumour­specific molecular targets. However, the role of miR­103a­3p in SACC remains largely unknown. In the present study, the expression levels of miR­103a­3p and tumour protein D52 (TPD52) were detected by reverse transcription­quantitative PCR. In addition, wound­healing assays, Transwell assays and mouse models of lung metastasis were used to investigate the biological functions exerted by miR­103a­3p. The present results suggested that miR­103a­3p expression was significantly upregulated in SACC samples. Gain­of­function and loss­of­function studies in SACC cells demonstrated that miR­103a­3p acted as an oncogene by promoting tumour cell migration in vitro and lung metastasis in vivo. Dual­luciferase reporter gene assays indicated that miR­103a­3p exerted its regulatory functions by binding to the 3' untranslated region of TPD52 mRNA. TPD52 overexpression rescued the effect of miR­103a­3p on promoting SACC cell migration, suggesting that miR­103a­3p acted as an oncogene to promote cancer metastasis by directly targeting TPD52. Thus, the newly identified miR­103a­3p/TPD52 axis contributes to the understanding of SACC pathogenesis, providing insights into the identification of novel biomarkers or potential therapeutic targets in SACC.

14.
Clin Rheumatol ; 2020 May 16.
Artigo em Inglês | MEDLINE | ID: mdl-32418039

RESUMO

Immune thrombocytopenia (ITP) is a common complication of connective tissue diseases (CTD). However, refractory and recurrent cases are frequent, who often need intensive immunotherapy. In the real world to compare the efficacy and safety of two common options, rituximab (RTX) and cyclosporine (CsA), in patients with refractory CTD-ITP, we conducted this retrospective study. Inpatients diagnosed with CTD-ITP who experienced treatment failure with initial prednisone or other immunosuppressants and who subsequently received either RTX or CsA between 2013 and 2018 were identified. All the patients were followed up for at least 6 months. Remission was defined as sustained platelet count ≥ 50 × 10^9/L, where ≥ 100 × 10^9/L was considered complete remission and 50-100 × 10^9/L was considered partial remission. Propensity score weighting analysis was performed to balance the confounders as indication. A total of 83 patients with CTD-ITP were identified, of whom 43 had systemic lupus erythematosus, 24 had undifferentiated CTD, and 16 had primary Sjogren syndrome. The RTX group (n = 53) had a much higher remission rate than the CsA group (n = 30) after 3 months and throughout the following 3 months (3 m, 86.8% vs 63.6%, p = 0.025; 6 m, 81.8% vs 53.5%, p = 0.011). Binary logistic regression analysis confirmed that treatment with RTX predicted better outcome (OR 4.09, 1.42 ~ 11.79), while age > 50 (OR 0.31, 0.11 ~ 0.93) was a risk factor. Furthermore, we reinforced the conclusions by propensity score weighting analysis (RTX OR 4.89, 1.64 ~ 14.58; age > 50 OR 0.31, 0.12 ~ 0.83). In our real-world retrospective study, for patients with refractory CTD-ITP, RTX was superior to CsA in terms of the durable remission rate.Key Points:• Refractory cases are common in patients with immune thrombocytopenia secondary to connective tissue diseases (CTD-ITP), requiring intensive immunotherapy.• Randomized controlled trials comparing rituximab and a traditional immunosuppressive agents (IS), such as cyclosporin, are lacking in these patients.• Our real-word retrospective study indicated that rituximab was superior to cyclosporin in patients with refractory CTD-ITP.

15.
Acta Pharmacol Sin ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451415

RESUMO

Lifestyle factors may affect mental health and play a critical role in the development of neurodegenerative diseases including Alzheimer's disease (AD). However, whether the temperatures of daily beverages have any impact on cognitive function and AD development has never been studied. In this study, we investigated the effects of daily drinking water temperatures on cognitive function and AD development and progression in mice and the underlying mechanisms. Cognitive function of mice was assessed using passive avoidance test, open field test, and Morris water maze. Wild-type Kunming mice receiving intragastric water (IW, 10 mL/kg, 2 times/day) at 0 °C for consecutive 15 days displayed significant cognitive defects accompanied by significant decrease in gain of body weight, gastric emptying rate, pepsin activity, and an increase in the energy charge in the cortex when compared with mice receiving the same amount of IW at 25 °C (a temperature mimicking most common drinking habits in human), suggesting the altered neuroenergetics may cause cognitive decline. Similarly, in the transgenic APPwse/PS1De9 familial AD mice and their age- and gender-matched wild-type C57BL/6 mice, receiving IW at 0 °C, but not at 25 °C, for 35 days caused a significant time-dependent decrease in body weight and cognitive function, accompanied by a decreased expression of PI3K, Akt, the glutamate/GABA ratio, as well as neuropathy with significant amyloid lesion in the cortex and hippocampus. All of these changes were significantly aggravated in the APPwse/PS1De9 mice than in the control C57BL/6 mice. These data demonstrate that daily beverage at 0 °C may alter brain insulin-mediated neuroenergetics, glutamate/GABA ratio, cause cognitive decline and neuropathy, and promote AD progression.

16.
Nat Plants ; 2020 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-32451445

RESUMO

The folding and assembly of RuBisCO, the most abundant enzyme in nature, needs a series of chaperones, including the RuBisCO accumulation factor Raf1, which is highly conserved in cyanobacteria and plants. Here, we report the crystal structures of Raf1 from cyanobacteria Anabaena sp. PCC 7120 and its complex with RuBisCO large subunit RbcL. Structural analyses and biochemical assays reveal that each Raf1 dimer captures an RbcL dimer, with the C-terminal tail inserting into the catalytic pocket, and further mediates the assembly of RbcL dimers to form the octameric core of RuBisCO. Furthermore, the cryo-electron microscopy structures of the RbcL-Raf1-RbcS assembly intermediates enable us to see a dynamic assembly process from RbcL8Raf18 to the holoenzyme RbcL8RbcS8. In vitro assays also indicate that Raf1 can attenuate and reverse CcmM-mediated cyanobacterial RuBisCO condensation. Combined with previous findings, we propose a putative model for the assembly of cyanobacterial RuBisCO coordinated by the chaperone Raf1.

17.
iScience ; 23(5): 101112, 2020 May 22.
Artigo em Inglês | MEDLINE | ID: mdl-32408176

RESUMO

In everyday life, people control objects in the world around them to varying degrees. The processes people actively use to establish their control, while interacting with an environment containing large ambiguity, remain unknown. This study examines how people explore their control over the environment and how they detect small differences in control among objects. In the experimental task, participants moved three dots on a screen and identified one dot over which the level of control is different from that of the other two. The results support a two-step behavior mechanism underlying the sensing of control difference: People first explore their overall control in the environment, and then the results of the initial exploration are used to selectively tune the direction (i.e., either more or less) of the detected control difference, ensuring efficient and rapid detection of the type of control difference that is potentially important for further action selections.

18.
Clin Interv Aging ; 15: 609-618, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32431494

RESUMO

Introduction: Elderly people are at increased risk of falls, disability and death due to reduced functional reserve, decline in multiple systems functions, which affects their activities of daily living (ADL) and eventually develop into frailty. The ADL assessment is conducive to early detection to avoid further serious situations. Previous studies on patients' activities of daily living with chronic kidney disease (CKD) are mainly focused on dialysis patients. Little information is available on non-dialysis patients. Patients and Methods: A total of 303 elderly patients with CKD stage 3-5 who were admitted to our hospital were selected. ADL evaluation was performed on patients at admission, with Barthel index (BI) as the evaluation tool. They were divided into two groups based on BI (≥60 and <60). Demographic information, lifestyle and clinical profile were collected. The risk factors related to ADL were analyzed by univariate and multivariate models. Results: The data of 303 patients enrolled in this study were analyzed. The average age of patients was 84.48± 7.14 years and 62.05% were male. There were 88 patients (29.04%) in BI <60 group and 215 patients (70.96%) in the BI ≥60 group. The average age of subjects in the two groups was 87.47 ± 5.85 years and 83.26± 7.28 years, respectively. On univariate analysis, ADL impairment was associated with many factors, such as age, body mass index, blood lipid, heart rate, smoking history, Charlson comorbidity index (CCI), hemoglobin, serum albumin, BNP, eGFR, etc. Multivariate logistic regression showed that age (OR 1.08, 95% CI 1.00-1.17, P=0.0390), Charlson comorbidity index (OR 4.75, 95% CI 1.17-19.30, P=0.0295), and serum albumin (OR 0.80, 95% CI 0.70-0.92, P=0.0012) were the independent risk factors of ADL impairment. Conclusion: Decline of ADL in CKD patients was independently correlated with age, Charlson comorbidity index and serum albumin. ADL and its influential factors in the elderly CKD patients deserve further attention.

19.
J Aging Phys Act ; : 1-8, 2020 May 29.
Artigo em Inglês | MEDLINE | ID: mdl-32470918

RESUMO

Outdoor fitness equipment (OFE) is installed in parks to promote health, particularly among seniors. However, no quantitative study has investigated its effectiveness. Therefore, this study aimed to examine the effectiveness of 12 weeks of OFE training on functional fitness in seniors. Forty-two active seniors were recruited and randomly assigned into OFE and control groups. The OFE group underwent 12 weeks of training using popular OFE for cardiorespiratory function, flexibility, and strength, whereas participants in the control group were asked to maintain their previous lifestyles. The senior fitness test was assessed before and after the 12-week period. Unexpectedly, the results showed no significant improvement within or between the groups after the 12-week training in all parameters (p > .05). In conclusion, the 12-week OFE training failed to enhance functional fitness among active seniors. Potential reasons for the limited training effects might be lack of resistance components and diversity of the OFE design and installation.

20.
FASEB J ; 34(5): 6570-6581, 2020 May.
Artigo em Inglês | MEDLINE | ID: mdl-32246801

RESUMO

Dysfunction of the circadian rhythm is one of most common nonmotor symptoms in Parkinson's disease (PD), but the molecular role of the circadian rhythm in PD is unclear. We here showed that inactivation of brain and muscle ARNT-like 1 (BMAL1) in 1-methyl-4-phenyl-1,2,4,5-tetrahydropyridine (MPTP)-treated mice resulted in obvious motor functional deficit, loss of dopaminergic neurons (DANs) in the substantia nigra pars compacta (SNpc), decrease of dopamine (DA) transmitter, and increased activation of microglia and astrocytes in the striatum. Time on the rotarod or calorie consumption, and food and water intake were reduced in the Bmal1-/- mice after MPTP treatment, suggesting that absence of Bmal1 may exacerbate circadian and PD motor function. We observed a significant reduction of DANs (~35%) in the SNpc, the tyrosine hydroxylase protein level in the striatum (~60%), the DA (~22%), and 3,4-dihydroxyphenylacetic acid content (~29%), respectively, in MPTP-treated Bmal1-/- mice. Loss of Bmal1 aggravated the inflammatory reaction both in vivo and in vitro. These findings suggest that BMAL1 may play an essential role in the survival of DANs and maintain normal function of the DA signaling pathway via regulating microglia-mediated neuroinflammation in the brain.

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