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1.
Oxid Med Cell Longev ; 2020: 5146982, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33014271

RESUMO

Acute lung injury (ALI) has gained increased attention in the field of critical illness research and is associated with a fatality rate of approximately 50%. Nuclear factor erythroid 2-related factor2 (Nrf2) is a key regulator of intracellular oxidation homeostasis and also functions as an antioxidant. It has been reported that Nrf2 associated antioxidant stress is closely related to ferroptosis inhibition. Signal transducer and activator of transcription 3 (STAT3) is activated into phosphorylated STAT3 (pSTAT3) in response to tissue damage and serves as a warning signal to enhance the inflammatory response. In this study, an intestinal ischemia/reperfusion-induced acute lung injury (IIR-ALI) model was established in C57BL/6 mice to investigate the role of Nrf2 in regulating IIR-ALI-associated ferroptosis. Compared with those in the IIR-ALI group, the injection of Fe (15 mg/kg) or ferrostatin-1 (5 mg/kg) (ferroptosis promoter and inhibitor, respectively) via the tail vein could aggravate or alleviate lung injury and pulmonary edema, respectively. Nrf2 was increased in IIR-ALI and promoted the phosphorylation of STAT3 to amplify downstream signals. An in vitro oxygen-glucose deprivation and reoxygenation (OGD-R) model was established in MLE12 cells to imitate the ischemia/reperfusion condition. The cells were transfected with lentiviruses to increase or downregulate the levels of STAT3. We found that Nrf2 and STAT3 played key roles in ferroptosis by regulating SLC7A11, which improved the pathological processes associated with ALI.

2.
Clin Interv Aging ; 15: 1767-1778, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33061328

RESUMO

Purpose: Injurious falls seriously threaten the safety of elderly patients. Identifying risk factors for predicting the probability of injurious falls is an important issue that still needs to be solved urgently. We aimed to identify predictors and develop a nomogram for distinguishing populations at high risk of injurious falls from older adults in acute settings. Patients and Methods: A retrospective case-control study was conducted at three hospitals in Shanghai, China. Elderly patients with injurious falls from January 2014 to December 2018 were taken as cases, and control patients who did not have falls were randomly matched based on the admission date and the department. The data were collected through a medical record review and adverse events system. The original data set was randomly divided into a training set and a validation set at a 7:3 ratio. A nomogram was established based on the results of the univariate analysis and multivariate logistic regression analysis, and its discrimination and calibration were verified to confirm the accuracy of the prediction. The cut-off value of risk stratification was determined to help medical staff identify the high-risk groups. Results: A total of 115 elderly patients with injurious falls and 230 controls were identified. History of fractures, orthostatic hypotension, functional status, sedative-hypnotics and level of serum albumin were independent risk factors for injurious falls in elderly patients. The C-indexes of the training and validation sets were 0.874 (95% CI: 0.784-0.964) and 0.847 (95% CI: 0.771-0.924), respectively. Calibration curves were drawn and showed acceptable predictive performance. The cut-off values of the training and validation sets were 146.3 points (sensitivity: 73.7%; specificity: 87.5%) and 157.2 points (sensitivity: 69.2%; specificity: 85.5%), respectively. Conclusion: The established nomogram facilitates the identification of high-risk populations among elderly patients, providing a new assessment tool to forecast the individual risk of injurious falls.

3.
J Biotechnol ; 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-33049356

RESUMO

Astaxanthin shows multiple biological activities, but it is usually linked to different fatty acids and exists in the form of esters. The complexity of astaxanthin esters limits their application in the preparation of sophisticated drugs. Herein, a novel lipase from Streptomyces bacillaris that could hydrolyze astaxanthin esters, named OUC-Sb-lip12, was expressed in Bacillus subtilis. The active site of OUC-Sb-lip12 is probably composed of a dyad of Ser48 and His254, instead of a typical catalytic triad. The lipase was identified to be a GDSL hydrolase, and it showed highest activity at 45 °C and pH 9.0 (glycine-NaOH buffer). OUC-Sb-lip12 showed a good stability at its optimum temperature or a higher temperature, retaining 88.4 % and 80.6 % of its activity after incubation for 36 h at 45 °C and 55 °C, respectively. OUC-Sb-lip12 could effectively hydrolyze astaxanthin esters in Haematococcus pluvialis oil, generating free astaxanthin. Under the optimum conditions, 96.29 % astaxanthin esters were hydrolyzed in 12 h. In addition, B.subtilis is a GRAS model strain and it could efficiently secrete lipase in 9 h, making the lipase potential for scale production of free astaxanthin, which could be further used in the preparation of specific astaxanthin esters with specific functions.

4.
BMC Musculoskelet Disord ; 21(1): 690, 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33076896

RESUMO

BACKGROUND: Lumbar disc herniation (LDH) is mainly caused by annular fiber disruption with a discrete leakage of nucleus pulposus pressing on a nerve, resulting in back pain and radiating pain. Most patients with LDH can be treated conservatively, but there are many different conservative treatments. Furthermore, most previous studies did not evaluate the long-term efficacy of these treatments and the prognosis. Therefore, an effective and safe therapeutic strategy is lacking for patients with LDH. In this study, we evaluated Xiao Sui Hua He decoction (XSHHD) in the treatment of LDH. METHODS: This was a rigorous prospective observational 3-year follow-up study. We recruited 69 participants with ruptured lumbar disc herniation (RLDH) between February 2014 and February 2016. Patients took XSHHD orally twice a day for 6 months. The primary outcome measurements were visual analogue scale (VAS) pain score, Oswestry disability index (ODI) and straight leg raising test (SLRT). The secondary outcome measurements was nucleus pulposus protrusion volume on magnetic resonance imaging (MRI). Clinical outcomes were measured at baseline (Visit 1), and at 3, 6, 12, and 36 months (Visit 2, 3, 4, and 5, respectively).. RESULTS: Sixty-three patients were followed-up for 3 years after treatment. SLRT and ODI after non-surgical treatment improved significantly compared with baseline (P < .001). There were no statistically significant differences at 6 months vs 36 months for SLRT and ODI. VAS scores (leg, back) after 3 years of treatment were statistically significantly different compared with baseline (P < .001; Z = - 6.93, - 6.637). The baseline protrusion volume was 2018.61 ± 601.16 mm3, and the volume decreased significantly to 996.51 ± 387.42 mm3 at 36 months (t = 12.863; P < .001). The volume of protrusion resorption rate (VPRR) at 36 months was 47.24 ± 23.99%, with significant resorption in 23 cases, partial resorption in 23 cases, no resorption in 15 cases, and increased volume in 2 cases. CONCLUSIONS: This study showed that non-surgical treatment with XSHHD was effective, and the study clarified the natural outcomes in LDH.

5.
Clin Lab ; 66(10)2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-33073966

RESUMO

BACKGROUND: To explore the expression of serum TLR4 and NF-κB levels in neonatal jaundice. METHODS: A total of 63 jaundice infants admitted to our hospital from January 2017 to January 2018 were enrolled into the experimental group (34 pathological jaundice infants and 29 physiological jaundice infants). The serum TLR4 level (0.5 ng/mL as positive expression) was determined by immunohistochemical staining, and the serum NF-κB level in peripheral blood was determined by ELISA. A total of 40 healthy infants with simultaneous blood sampling and physical examination were enrolled into the control group to measure the levels of TLR4 and NF-κB which were compared between the two groups. RESULTS: The levels of serum TLR4 and NF-κB in the infants in the experimental group were higher than those in normal newborns in the same period, the difference between the two groups was statistically significant (p < 0.05), and the levels of TLR4 and NF-κB showed a gradual downtrend after treatment. TLR4 expressions were positive in pathologic and physiologic jaundice infants of the experimental group, and negative in the control group. The correlation analysis showed that the elevated levels of TLR4, NF- kb, IL-Iß, and TNF-α were risk factors for jaundice. CONCLUSIONS: The elevated levels of TLR4 and NF-κB are the main factors of neonatal jaundice. TLR4, NF- kb, IL-Iß, and TNF-α are closely related to the onset of jaundice, which can be used as an important marker in clinical diagnosis of neonatal jaundice.

6.
J Integr Neurosci ; 19(3): 495-499, 2020 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-33070529

RESUMO

This paper describes the genetic etiology of sporadic amyotrophic lateral sclerosis in a single population. Polymerase chain reaction-restriction fragment length polymorphism and DNA sample sequencing of 3 common HFE gene variants (C282Y and H63D and S65C) were performed on 10 randomly selected samples of H63D gene variant (124 patients with sporadic amyotrophic lateral sclerosis) and 10 wild types of H63D samples (210 controls). The C282Y and S65C gene variant were absent. There were 24 cases (7.18%) with H63D heterozygous variants, including 16 cases (13%) in the sporadic amyotrophic lateral sclerosis group and 8 cases (4%) in the healthy control group. The polymorphism frequency of the H63D gene variant in the sporadic amyotrophic lateral sclerosis group was significantly different than that in the control group (p < 0.05), and the difference at allele level, which is still more significant (p < 0.05). H63D gene variant could be a risk factor for sporadic amyotrophic lateral sclerosis in a single population. The results showed HFE gene variants play a role in the occurrence of sporadic amyotrophic lateral sclerosis, but its effect should be carefully estimated.

7.
Virol Sin ; 2020 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-33074475

RESUMO

Hantavirus infection is a global health challenge, causing widespread public concern. In recent years, cases of hantavirus infection in pregnant women have been reported in many countries. The infected pregnant women and their fetuses appear to have more severe clinical symptoms and worse clinical outcomes. Hence, to study the prevalence of hantavirus infection in pregnant women, this study will focus on the epidemiological distribution of the virus, different virus species penetrating the placental barrier, and factors affecting the incidence and clinical outcome of the infection in pregnant women and their fetuses. In addition, this review will also discuss the diagnostic tools and treatments for pregnant patients and provide an overview of the relevant future research.

8.
Ageing Res Rev ; 64: 101187, 2020 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-33007437

RESUMO

Growth hormone secretagogue receptor 1a (GHSR1a), a member of the G protein-coupled receptor (GPCR) family, is a functional receptor of ghrelin. The expression levels and activities of GHSR1a are affected by various factors. In past years, it has been found that the ghrelin-GHSR1a system can perform biological functions such as anti-inflammation, anti-apoptosis, and anti-oxidative stress. In addition to mediating the effect of ghrelin, GHSR1a also has abnormally high constitutive activity; that is, it can still transmit intracellular signals without activation of the ghrelin ligand. This constitutive activity affects brain functions, growth and development of the body; therefore, it has profound impacts on neurodegenerative diseases and some other age-related diseases. In addition, GHSR1a can also form homodimers or heterodimers with other GPCRs, affecting the release of neurotransmitters, appetite regulation, cell proliferation and insulin release. Therefore, further understanding of the constitutive activities and dimerization of GHSR1a will enable us to better clarify the characteristics of GHSR1a and provide more therapeutic targets for drug development. Here, we focus on the roles of GHSR1a in various biological functions and provide a comprehensive summary of the current research on GHSR1a to provide broader therapeutic prospects for age-related disease treatment.

9.
Zhongguo Ying Yong Sheng Li Xue Za Zhi ; 36(3): 235-239, 2020 May.
Artigo em Chinês | MEDLINE | ID: mdl-32981278

RESUMO

Objective: To investigate the effects of exogenous NaHS on myelin basic protein (MBP) and learning and memory of hippocampal neurons in mice with spinocerebellar ataxia type 3 (SCA3) and its therapeutic significance.Methods: Twelve male normal mice were randomly selected as normal control group (NC Group), and 48 SCA3 mice were randomly selected as SCA3 model group (M Group), low dose group (NL Group, 10 µmol/kg), medium dose group (NM Group, 50µmol/kg) and high dose group (NH Group, 100 µmol/kg), 12 rats in each group. The drug treated groups were injected with NaHS intraperitoneally once a day for 4 weeks. The changes of learning and memory ability of SCA3 mice before and after the intervention of different doses of NaHS were determined by Morris water maze, the content of hydrogen sulfide (H2S) in hippocampus was measured by spectrophotometry, the expression of MBP was detected by immunohistochemistry, and the morphological changes of neuron myelin sheath were observed by electron microscope. Results: Compared with the control group, the learning and memory ability of SCA3 mice was decreased significantly (P<0.05), and the content of H2S in hippocampus was decreased (P<0.05). After different doses of exogenous NaHS treatment, the learning and memory ability was improved in different degrees (P<0.05), and the contents of H2S and MBP in hippocampus of SCA3 mice were also improved in different degrees (P<0.05). Conclusion: Exogenous NaHS may increase the contents of H2S and MBP in the hippocampus of SCA3 mice, which may have a protective effect on the neurons, and then improve the learning and memory ability of SCA3 mice, and provide a new idea for the treatment of SCA3.

10.
Sci Rep ; 10(1): 15542, 2020 Sep 23.
Artigo em Inglês | MEDLINE | ID: mdl-32968192

RESUMO

Abnormal iron accumulation caused by elevated levels of divalent metal transporter 1 (DMT1) contributes to progressive neurodegeneration in Parkinson's disease (PD). Parkin is a E3 ubiquitin ligase for the ubiquitination of DMT1. S-nitrosylated parkin (SNO-parkin) is commonly observed in PD. However, the effects of S-nitrosylation on the E3 ubiquitin ligase activity of parkin for the ubiquitination of DMT1 in PD are largely unknown. To elucidate the role of S-nitrosylated parkin and DMT1 in PD, SH-SY5Y cells were transfected with parkin, being treated with S-nitrosoglutathione (GSNO) and 1-methyl-4-phenylpyridinium (MPP+). The results showed increased levels of oxidized nitric oxide (NO) and S-nitrosylated parkin after the treatment of GSNO and MPP+ in parkin-transfected cells. Consistently, increased levels of DMT1, iron uptake and cell viability were observed. Interestingly, inhibition of S-nitrosylated parkin reduced the level of DMT1. Further, S-nitrosylation of parkin significantly inhibited the ubiquitination of DMT1. When HEK293T cells were transfected with plasmid of parkin with single site mutation (Cys241A, Cys260A, Cys323A), ubiquitination of DMT1 was also inhibited. However, the cells cotransfected with plasmids containing all three mutations, GSNO treatment did not affect the ubiquitination of DMT1. The expression of SNO-parkin and DMT1 protein in substantia nigra increased significantly gradually after 2 h, 4 h and 24 h with MPTP injection. These results indicate that the S-nitrosylation of parkin inhibits its E3 ubiquitin ligase activity for the ubiquitination of DMT1, which contributes to iron accumulation and degenerative process in PD. Targeted S-nitrosylation could provide a potential therapeutic strategy against PD.

11.
Zhongguo Gu Shang ; 33(8): 750-7, 2020 Aug 25.
Artigo em Chinês | MEDLINE | ID: mdl-32875767

RESUMO

OBJECTIVE: To explore the risk factors of osteonecrosis of femoral head after internal fixation of femoral neck fracture in young patients, to describe the quality of life of patients with surviving femoral head, and to quantify the predictive factors. METHODS: From January 2013 to December 2016, 172 patients (174 hips) with femoral neck fracture treated by closed reduction and cannulated screw internal fixation were selected for retrospective analysis. The general data of the patients were summarized, including age, gender, body mass index, trauma mechanism, trauma operation interval, trauma season and whether the internal fixation was removed. The imaging data included the Garden classification and Pauwel classification of fractures, femoral head retroversion angle, postoperative fracture reduction, screw distribution. Single factor analysis and multi-factor Logistic regression analysis were carried out to explore the risk factors of femoral head necrosis and internal fixation failure. The patients who survived the internal fixation were followed up. The quality of life of the patients was evaluated by the health survey of SF-36. The Harris score of hip joint function was used to evaluate the hip joint function. The predictors of the quality of life of the patients after the operation of femoral neck fracture were analyzed by multiple linear regression analysis. RESULTS: Total 172 patients(174 hips) were included in the study, 29 patients(16.67%) had necrosis of the femoral head. In multivariate Logistic regression analysis, the significant differences were reduction quality (OR=0.126, P=0.027) and posterior inclination angle (OR=4.380, P=0.010). One hundred and thirty six patients (137 hips) who survived the femoral head were included in the quality of life survey. Harris score was 90.14±7.92, including excellent 96 hips (70.07%), good 28 hips (20.44%), medium 13 hips (9.49%) and poor 0 hip. In SF-36 score, physical health summary (PCS) was 46.12±9.12, mental health summary(MCS) was 50.21±3.97, there was no linear correlation between them (P>0.05). In multiple linear regression analysis, the variables with significant difference in PCS were reduction quality and retroversion angle, and the variables with significant difference in MCS were fracture displacement and trauma mechanism. CONCLUSION: Poor reduction quality and posterior inclination angle>15° are the risk factors of femoral head necrosis. The function of hip joint and MCS of patients with femoral neck fracture recovered well, but PCS could not recover to the average level of normal people. The reduction quality and retroversion angle could be used as the predictors of PCS, and the displacement and trauma mechanism of fracture could be used as the predictors of MCS.


Assuntos
Fraturas do Colo Femoral , Osteonecrose , Cabeça do Fêmur , Fixação Interna de Fraturas , Humanos , Qualidade de Vida , Estudos Retrospectivos
12.
Oxid Med Cell Longev ; 2020: 9343160, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32963707

RESUMO

Background: Neuroinflammation plays a key role in myocardial ischemia-reperfusion (I/R) injury. Previous studies showed that light-emitting diode (LED) therapy might improve M2 microglia activation and brain-derived neurotrophic factor (BDNF) expression, thereby exerting anti-inflammatory effects. Therefore, we hypothesized that LED therapy might reduce myocardial I/R injury by neuroinflammation modulation. Objective: To explore the effect of LED therapy on myocardial I/R-induced injury and seek the underlying mechanism. Methods: Thirty rats were randomly divided into three groups: Control group (without LED treatment or myocardial I/R, n = 6), I/R group (with myocardial I/R only, n = 12), and LED+I/R group (with myocardial I/R and LED therapy, n = 12). Electrocardiogram was recorded continuously during the procedure. In addition, brain tissue was extracted for BDNF, Iba1, and CD206 analyses, and heart tissue for myocardial injury (ischemic size and infarct size), IL-4 and IL-10 mRNA analysis. Results: In comparison with the I/R group, the ischemia size and the infarct size were significantly attenuated by LED therapy in the LED+I/R group. Meanwhile, the microglia activation induced by I/R injury was prominently attenuated by LED treatment either. And it is apparent that there was also an increase in the beneficial neuroinflammation markers (BDNF and CD206) in the paraventricular nucleus (PVN) in the LED+I/R group. Furthermore, the anti-inflammatory cytokines, IL-4 and IL-10, were greatly decreased by I/R while improved by LED treatment in myocardium. Conclusion: LED therapy might reduce neuroinflammation in PVN and decrease myocardium injury by elevating BDNF and M2 microglia.

13.
Acta Pharm Sin B ; 10(8): 1426-1439, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32963941

RESUMO

The membrane protein claudin-3 (CLDN3) is critical for the formation and maintenance of tight junction and its high expression has been implicated in dictating malignant progression in various cancers. However, the post-translational modification of CLDN3 and its biological function remains poorly understood. Here, we report that CLDN3 is positively correlated with ovarian cancer progression both in vitro and in vivo. Of interest, CLDN3 undergoes S-palmitoylation on three juxtamembrane cysteine residues, which contribute to the accurate plasma membrane localization and protein stability of CLDN3. Moreover, the deprivation of S-palmitoylation in CLDN3 significantly abolishes its tumorigenic promotion effect in ovarian cancer cells. By utilizing the co-immunoprecipitation assay, we further identify ZDHHC12 as a CLDN3-targating palmitoyltransferase from 23 ZDHHC family proteins. Furthermore, the knockdown of ZDHHC12 also significantly inhibits CLDN3 accurate membrane localization, protein stability and ovarian cancer cells tumorigenesis. Thus, our work reveals S-palmitoylation as a novel regulatory mechanism that modulates CLDN3 function, which implies that targeting ZDHHC12-mediated CLDN3 S-palmitoylation might be a potential strategy for ovarian cancer therapy.

14.
Ann Neurol ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32939785

RESUMO

OBJECTIVE: A recessive biallelic repeat expansion, (AAGGG)exp , in the RFC1 gene has been reported to be a frequent cause of late-onset ataxia. For cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS), the recessive biallelic (AAGGG)exp genotype was present in ~92% of cases. This study aimed to examine whether the pentanucleotide repeat (PNR) was related to multiple system atrophy (MSA), which shares a spectrum of symptoms with CANVAS. METHODS: In this study, we screened the pathogenic (AAGGG)exp repeat and 5 other PNRs in 104 Chinese sporadic adult-onset ataxia of unknown aetiology (SAOA) patients, 282 MSA patients, and 203 unaffected individuals. Multiple molecular genetic tests were used, including long-range polymerase chain reaction (PCR), repeat-primed PCR (RP-PCR), Sanger sequencing, and Southern blot. Comprehensive clinical assessments were conducted, including neurological examination, neuroimaging, nerve electrophysiology, and examination of vestibular function. RESULTS: We identified biallelic (AAGGG)exp in 1 SAOA patient and 3 MSA patients. Additionally, 1 MSA patient had the (AAGGG)exp /(AAAGG)exp genotype with uncertain pathogenicity. We also described the carrier frequency for different PNRs in our cohorts. Furthermore, we summarized the distinct phenotypes of affected patients, suggesting that biallelic (AAGGG)exp in RFC1 could be associated with MSA and should be screened routinely in the MSA diagnostic workflow. INTERPRETATION: Our results expanded the clinical phenotypic spectrum of RFC1-related disorders and raised the possibility that MSA might share the same genetic background as CANVAS, which is crucial for re-evaluating the current CANVAS and MSA diagnostic criteria. ANN NEUROL 2020.

15.
Ageing Res Rev ; : 101174, 2020 Sep 21.
Artigo em Inglês | MEDLINE | ID: mdl-32971255

RESUMO

One of the key issues facing public healthcare is the global trend of an increasingly ageing society which continues to present policy makers and caregivers with formidable healthcare and socio-economic challenges. Ageing is the primary contributor to a broad spectrum of chronic disorders all associated with a lower quality of life in the elderly. In 2019, the Chinese population constituted 18 % of the world population, with 164.5 million Chinese citizens aged 65 and above (65+), and 26 million aged 80 or above (80+). China has become an ageing society, and as it continues to age it will continue to exacerbate the burden borne by current family and public healthcare systems. Major healthcare challenges involved with caring for the elderly in China include the management of chronic non-communicable diseases (CNCDs), physical frailty, neurodegenerative diseases, cardiovascular diseases, with emerging challenges such as providing sufficient dental care, combating the rising prevalence of sexually transmitted diseases among nursing home communities, providing support for increased incidences of immune diseases, and the growing necessity to provide palliative care for the elderly. At the governmental level, it is necessary to make long-term strategic plans to respond to the pressures of an ageing society, especially to establish a nationwide, affordable, annual health check system to facilitate early diagnosis and provide access to affordable treatments. China has begun work on several activities to address these issues including the recent completion of the of the Ten-year Health-Care Reform project, the implementation of the Healthy China 2030 Action Plan, and the opening of the National Clinical Research Center for Geriatric Disorders. There are also societal challenges, namely the shift from an extended family system in which the younger provide home care for their elderly family members, to the current trend in which young people are increasingly migrating towards major cities for work, increasing reliance on nursing homes to compensate, especially following the outcomes of the 'one child policy' and the 'empty-nest elderly' phenomenon. At the individual level, it is important to provide avenues for people to seek and improve their own knowledge of health and disease, to encourage them to seek medical check-ups to prevent/manage illness, and to find ways to promote modifiable health-related behaviors (social activity, exercise, healthy diets, reasonable diet supplements) to enable healthier, happier, longer, and more productive lives in the elderly. Finally, at the technological or treatment level, there is a focus on modern technologies to counteract the negative effects of ageing. Researchers are striving to produce drugs that can mimic the effects of 'exercising more, eating less', while other anti-ageing molecules from molecular gerontologists could help to improve 'healthspan' in the elderly. Machine learning, 'Big Data', and other novel technologies can also be used to monitor disease patterns at the population level and may be used to inform policy design in the future. Collectively, synergies across disciplines on policies, geriatric care, drug development, personal awareness, the use of big data, machine learning and personalized medicine will transform China into a country that enables the most for its elderly, maximizing and celebrating their longevity in the coming decades. This is the 2nd edition of the review paper (Fang EF et al., Ageing Re. Rev. 2015).

16.
Curr Vasc Pharmacol ; 2020 Sep 16.
Artigo em Inglês | MEDLINE | ID: mdl-32940182

RESUMO

Nicotinic acetylcholine receptors (nAChRs) comprise a large family of ligand-gated ion channels that have a broad distribution in neurons and non-neuronal cells throughout the body. Native nAChRs, activated by acetylcholine (ACh) endogenously, are involved in a variety of physiological and pathophysiological processes. They regulate processes necessary for network operations through neurotransmitter release, cell excitability and neuronal integration. Emerging evidence suggests that nAChRs are capable of regulating cardiovascular (CV) functions in a cell type-specific manner, through the nervous system and non-neuronal tissues. The aim of this review is to describe the most recent findings regarding the role of nAChRs inside and outside the nervous system in the regulation of CV activities.

17.
Thorac Cancer ; 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32945092

RESUMO

BACKGROUND: The aim of the study was to investigate 3D texture analysis (3D-TA) in noncontrast enhanced computed tomography (CT) (NCECT) to differentiate squamous cell carcinoma (SCC) from adenocarcinoma (AC), and the correlation with immunohistochemical markers. METHODS: A total of 70 patients confirmed with SCC (n = 29) and AC (n = 41) were enrolled in this retrospective study. 3D-TA was utilized to calculate TA parameters of all the tumor lesions based on NCECT images, and all the patients were divided into the training and the test groups. The TA parameters were selected by dimensionality reduction, and the model was established to differentiate SCC from AC according to the training group. The ROC curve was used to evaluate the diagnostic efficiency of the model in both the training and the test groups. Spearman correlation were used to assess the correlation between the selected feature parameters and immunohistochemical markers (P63, P40, and TTF-1). RESULTS: Five TA parameters, including volume count, relative deviation, Haralick correlation, gray-level nonuniformity and run length nonuniformity, were obtained to differentiate SCC from AC by multistep dimensionality reduction. The new model combined with all five TA parameters yielded a high diagnostic performance to differentiate SCC from AC (AUC 0.803) in test group, with a specificity of 89% and a sensitivity of 77%. There was weak correlation between the five texture feature parameters and P63 as well as P40 in all patients (P < 0.05), respectively. CONCLUSIONS: The model including five TA parameters on NECT has a good diagnostic performance in differentiating SCC from AC. KEY POINTS: • Significant findings of the study The model created by five selected textural feature parameters can differentiate solid SCC from AC without contrast media. The selected five texture feature parameters are correlated to the immunohistochemical markers P63 and P40. • What this study adds The textural feature parameters' model can identify SCC from AC without contrast media.

18.
Parkinsonism Relat Disord ; 80: 65-72, 2020 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-32961396

RESUMO

INTRODUCTION: Genetic inheritance plays key roles in patients with ataxia and/or spastic paraplegia in consanguineous families. This study aims to clarify the genetic spectrum of patients with autosomal recessive hereditary ataxia and spastic paraplegias (AR-HA/HSPs) in consanguineous families. METHODS: A total of 36 AR-HA/HSPs consanguineous pedigrees from China were recruited into this study. Next generation sequencing (NGS), guided by homozygosity mapping (HM), was applied to identify the pathogenic variants in known genes or novel candidate genes. RESULTS: We totally made molecular diagnosis in 47.2% (17/36) of AR-HA/HSPs families. Among them, 13 AR-HAs carried pathogenic variants in SETX (n = 4), SACS (n = 2), STUB1, HSD17B4, NEU1, ADCK3, TPP1, PLA2G6 and MTCL1, while four AR-HSPs carried pathogenic variants in SPG11, ZFYVE26, ATP13A2 and ABCD1. One homozygous nonsense mutation in MRPS27 was identified in an AR-HA family, which was potentially a novel candidate gene of AR-HA. CONCLUSION: HM and NGS can serve as an efficient molecular diagnostic tool for AR-HA/HSPs in consanguineous families. Our findings provide a better understanding of genetic architecture of AR-HA/HSPs in consanguinity and broaden the clinical-genetic spectrum of the disease.

19.
J Mol Cell Cardiol ; 149: 73-81, 2020 Sep 22.
Artigo em Inglês | MEDLINE | ID: mdl-32971072

RESUMO

BACKGROUND: Persistent cardiac Ca2+/calmodulin dependent Kinase II (CaMKII) activation plays an essential role in heart failure development. However, the molecular mechanisms underlying CaMKII induced heart failure progression remains incompletely understood. Histone deacetylases (HDACs) are critical for transcriptional responses to stress, and contribute to expression of pathological genes causing adverse ventricular remodeling. Class I HDACs, including HDAC1, HDAC2 and HDAC3, promote pathological cardiac hypertrophy, whereas class IIa HDACs suppress cardiac hypertrophy. While it is known that CaMKII deactivates class IIa HDACs to enhance cardiac hypertrophy, the role of CaMKII in regulating class I HDACs during heart failure progression is unclear. METHODS AND RESULTS: CaMKII increases the deacetylase activity of recombinant HDAC1, HDAC2 and HDAC3 via in vitro phosphorylation assays. Phosphorylation sites on HDAC1 and HDAC3 are identified with mass spectrometry. HDAC1 activity is also increased in cardiac-specific CaMKIIδC transgenic mice (CaMKIIδC-tg). Beyond post-translational modifications, CaMKII induces HDAC1 and HDAC3 expression. HDAC1 and HDAC3 expression are significantly increased in CaMKIIδC-tg mice. Inhibition of CaMKII by overexpression of the inhibitory peptide AC3-I in the heart attenuates the upregulation of HDAC1 after myocardial infarction surgery. Importantly, a potent HDAC1 inhibitor Quisinostat improves downregulated autophagy genes and cardiac dysfunction in CaMKIIδC-tg mice. In addition to Quisinostat, selective class I HDACs inhibitors, Apicidin and Entinostat, HDAC3 specific inhibitor RGFP966, as well as HDAC1 and HDAC3 siRNA prevent CaMKII overexpression induced cardiac myocyte hypertrophy. CONCLUSION: CaMKII activates class I HDACs in heart failure, which may be a central mechanism for heart failure progression. Selective class I HDACs inhibition may be a novel therapeutic avenue to alleviate CaMKII hyperactivity induced cardiac dysfunction.

20.
J Int Med Res ; 48(9): 300060520959485, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32996793

RESUMO

OBJECTIVE: Craniocerebral injury has high disability and mortality rates. The timing of cranioplasty has an important impact on patients' prognosis. This study was performed to compare the functional prognosis between super early repair and conventional repair. METHODS: This observational study included 60 patients who underwent cranioplasty after surgical treatment of severe craniocerebral trauma. The patients were divided into two groups according to the time of cranial repair after the surgical treatment of craniocerebral injury: the super early group and the conventional repair group. Sex, age, Karnofsky performance status (KPS) score, Zubrod performance status (ZPS) score, psychological function score, quality of life score, and complications were recorded. RESULTS: The KPS score, ZPS score, psychological function score, and quality of life score were significantly related to the intervention period. Each of these scores had a clear correlation with the performance of super early treatment. CONCLUSION: Super early cranial repair does not increase the incidence of surgical complications, and it can improve the postoperative KPS, ZPS, and quality of life scores.

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