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1.
Int J Biol Sci ; 18(2): 731-741, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35002521

RESUMO

Rationale: Myocardial ischemia/reperfusion (I/R) injury is a common clinic scenario that occurs in the context of reperfusion therapy for acute myocardial infarction (AMI). The mitochondrial F1Fo-ATPase inhibitory factor 1 (IF1) blocks the reversal of the F1Fo-ATP synthase to prevent detrimental consumption of cellular ATP and associated demise. In the present study, we study the role and mechanism of IF1 in myocardial I/R injury. Methods: Mice were ligated the left anterior descending coronary artery to build the I/R model in vivo. Rat hearts were isolated and perfused with constant pressure according to Langendorff. Also, neonatal cardiomyocytes hypoxia-reoxygenation (H/R) model was also used. Myocardial infarction area, cardiac function, cellular function, and cell viability was conducted and compared. Results: Our data revealed that IF1 is upregulated in hearts after I/R and cardiomyocytes with hypoxia/re-oxygenation (H/R). IF1 delivered with adenovirus and adeno-associated virus serotype 9 (AAV9) ameliorated cardiac dysfunction and pathological development induced by I/R ex vivo and in vivo. Mechanistically, IF1 stimulates glucose uptake and glycolysis activity and stimulates AMPK activation during in vivo basal and I/R and in vitro OGD/R conditions, and activation of AMPK by IF1 is responsible for its cardioprotective effects against H/R-induced injury. Conclusions: These results suggest that increased IF1 in the I/R heart confer cardioprotective effects via activating AMPK signaling. Therefore, IF1 can be used as a potential therapeutic target for the treatment of pathological ischemic injury and heart failure.

2.
Mol Neurobiol ; 2022 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-34984583

RESUMO

Parkinson's disease (PD) is an incurable neurodegenerative disease characterized by aggregation of pathological alpha-synuclein (α-syn) and loss of dopaminergic neuron in the substantia nigra. Inhibition of phosphorylation of the α-syn has been shown to mediate alleviation of PD-related pathology. Protein phosphatase 2A (PP2A), an important serine/threonine phosphatase, plays an essential role in catalyzing dephosphorylation of the α-syn. Here, we identified and validated cancerous inhibitor of PP2A (CIP2A), as a potential diagnostic biomarker for PD. Our data showed that plasma CIP2A concentrations in PD patients were significantly lower compared to age- and sex-matched controls, 1.721 (1.435-2.428) ng/ml vs 3.051(2.36-5.475) ng/ml, p < 0.0001. The area under the curve of the plasma CIP2A in distinguishing PD from the age- and sex-matched controls was 0.776. In addition, we evaluated the role of CIP2A in PD-related pathogenesis in PD cellular and MPTP-induced mouse model. The results demonstrated that CIP2A is upregulated in PD cellular and MPTP-induced mouse models. Besides, suppression of the CIP2A expression alleviates rotenone induced aggregation of the α-syn as well as phosphorylation of the α-syn in SH-SY5Y cells, which is associated with increased PP2A activity. Taken together, our data demonstrated that CIP2A plays an essential role in the mechanisms related to PD development and might be a novel PD biomarker.

3.
J Control Release ; 341: 215-226, 2021 Nov 22.
Artigo em Inglês | MEDLINE | ID: mdl-34822908

RESUMO

Although the individual role of ligand modification or rigidity modulation on oral administration of nanoparticle (NP) has been investigated, how they mutually affect each other remains to be elucidated. Here, we fabricated different rigidity NP with or without surface decoration of FcBP, a neonatal Fc receptor domain-binding peptide. In vitro studies showed that, without FcBP modification, stiff NP had higher transcytosis efficiency across the epithelium than softer NP, due to the different endocytosis mechanisms, intracellular trafficking routes, and exocytosis rate. Notably, after FcBP modification, such difference was narrowed, in a manner that was more favorable for softer NP to "catch up" with stiff NP, suggesting ligand modification was more conducive to exert transcytosis-promoting efficacy on softer NP. In vivo experiments demonstrated that, for ligand-free NP, high rigidity was required for efficient oral absorption and liver distribution. Further FcBP modification decreased that "rigidity threshold", and expanded the feasible rigidity range from stiff NP to softer NP. Upon oral administration, FcBP-modified dexamethasone-loaded softer NP achieved a therapeutic efficacy comparable with stiff NP on alleviating liver fibrosis. Collectively, our study highlighted the necessity of coordinating ligand modification and rigidity modulation for oral drug delivery.

4.
J Refract Surg ; 37(10): 715-719, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34661477

RESUMO

PURPOSE: To describe the results of a relifting flap enhancement procedure for correction of residual refractive error after primary lenticule intrastromal keratoplasty (LIKE). METHODS: Case report. RESULTS: One year after a LIKE procedure in the left eye, the patient (uncorrected distance visual acuity [UDVA]: 20/25; corrected distance visual acuity [CDVA]: 20/20; manifest refraction: -1.00 +1.00 × 105°) underwent flap relifting. The WaveLight EX500 excimer laser platform (Alcon Laboratories, Inc) was used for the topography-guided enhancement procedure to correct the residual refractive error and corneal irregularities. During the 1-year follow-up period, the cornea remained clear, the UDVA increased to 20/20 (reaching the level of preoperative CDVA), and manifest refraction was -0.25 +0.75 × 90°. CONCLUSIONS: The enhancement procedure described in this case report was effective for correction of residual refractive error and improvement of visual acuity following the LIKE procedure. The enhancement was stable for at least 15 months after the procedure. [J Refract Surg. 2021;37(10):715-719.].


Assuntos
Refração Ocular , Procedimentos Cirúrgicos Refrativos , Topografia da Córnea , Humanos , Lasers de Excimer/uso terapêutico , Acuidade Visual
5.
BMC Med Inform Decis Mak ; 21(1): 283, 2021 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-34654419

RESUMO

BACKGROUND: The liver is an important organ that undertakes the metabolic function of the human body. Liver cancer has become one of the cancers with the highest mortality. In clinic, it is an important work to extract the liver region accurately before the diagnosis and treatment of liver lesions. However, manual liver segmentation is a time-consuming and boring process. Not only that, but the segmentation results usually varies from person to person due to different work experience. In order to assist in clinical automatic liver segmentation, this paper proposes a U-shaped network with multi-scale attention mechanism for liver organ segmentation in CT images, which is called MSA-UNet. Our method makes a new design of U-Net encoder, decoder, skip connection, and context transition structure. These structures greatly enhance the feature extraction ability of encoder and the efficiency of decoder to recover spatial location information. We have designed many experiments on publicly available datasets to show the effectiveness of MSA-UNet. Compared with some other advanced segmentation methods, MSA-UNet finally achieved the best segmentation effect, reaching 98.00% dice similarity coefficient (DSC) and 96.08% intersection over union (IOU).


Assuntos
Processamento de Imagem Assistida por Computador , Neoplasias , Humanos , Fígado/diagnóstico por imagem , Tomografia Computadorizada por Raios X
6.
Front Immunol ; 12: 719807, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34691027

RESUMO

According to emerging studies, the excessive activation of microglia and the subsequent release of pro-inflammatory cytokines play important roles in the pathogenesis and progression of Parkinson's disease (PD). However, the exact mechanisms governing chronic neuroinflammation remain elusive. Findings demonstrate an elevated level of NLRP3 inflammasome in activated microglia in the substantia nigra of PD patients. Activated NLRP3 inflammasome aggravates the pathology and accelerates the progression of neurodegenerative diseases. Abnormal protein aggregation of α-synuclein (α-syn), a pathologically relevant protein of PD, were reported to activate the NLRP3 inflammasome of microglia through interaction with toll-like receptors (TLRs). This eventually releases pro-inflammatory cytokines through the translocation of nuclear factor kappa-B (NF-κB) and causes an impairment of mitochondria, thus damaging the dopaminergic neurons. Currently, therapeutic drugs for PD are primarily aimed at providing relief from its clinical symptoms, and there are no well-established strategies to halt or reverse this disease. In this review, we aimed to update existing knowledge on the role of the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis and microglial activation in PD. In addition, this review summarizes recent progress on the α-syn/TLRs/NF-κB/NLRP3 inflammasome axis of microglia as a potential target for PD treatment by inhibiting microglial activation.

7.
Clin Neurol Neurosurg ; 210: 106950, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34583274

RESUMO

OBJECTIVE: Contralateral subdural effusion after decompressive craniectomy (CSEDC) is rare, and the optimal treatment is not determined. We present 11 cases of CSEDC and give an overview of the English literature pertaining to this disease. METHODS: We searched the database at our institution and performed a search of English literature in PubMed and Google Scholar. Keywords used were as follows (single word or combination): "subdural hygroma"; "subdural effusion"; "decompressive craniectomy". Only patients with CSEDC and contained adequate clinical information pertinent to the analysis were included. RESULTS: 11 cases of CSEDC were recorded at our institution. They comprised ten men and one woman with an average age of 41.9 years. All the 8 symptomatic patients underwent surgery and the CSEDC resolved gradually. 68 cases of CSEDC were found in the literature. Including ours, a total of 79 patients were analyzed. Conservative treatment was effective in the asymptomatic patients. 41.7% of the symptomatic CSEDC underwent burr hole drainage and successfully drained the CSEDC. However, 76% of them received subsequent surgery to manage the reaccumulation of CSEDC. 25% of the symptomatic patients underwent cranioplasty, while 13.3% of them received Ommaya drainage later because of CSEDC recurrence. 18.3% of the symptomatic patients underwent cranioplasty plus subduroperitoneal shunting, and all CSEDC resolved completely. CONCLUSIONS: Burr hole drainage appears to be only a temporary measure. Early cranioplasty should be performed for patients with CSEDC. CSF shunting procedures may be required for patients in whom CSEDC have not been solved or hydrocephalus manifest after cranioplasty.

8.
Mol Med Rep ; 24(5)2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34490487

RESUMO

Cardiac inflammation serves an important role in the progression of diabetic cardiomyopathy. CD36 (cluster of differentiation 36) mediates inflammation stress in a variety of disease states. The present study investigated CD36 expression in high glucose (HG)­induced H9c2 cells, whether CD36 upregulation promotes inflammatory stress, and its potential mechanism. HG induced CD36 expression in a time­dependent manner in cells, which was blocked following CD36 knockout or treatment with N­acetylcysteine or MitoTEMPO. CD36 translocation to the cell membrane was increased at 72 h by HG stimulation of H9c2 cells. Moreover, CD36 knockout inhibited HG­induced reactive oxygen species (ROS) generation, tumor necrosis factor­α, interleukin (IL)­6 and IL­1ß expression, and nuclear factor (NF)­κB pathway activation. Further, CD36 knockout reversed metabolic reprogramming, lipid accumulation and AMP­activated protein kinase activation caused by HG. The aforementioned data suggest that HG­induced upregulation of CD36 promotes inflammatory stress via NF­κB in H9c2 cells, mediated by metabolism reprogramming, lipid accumulation and enhanced ROS generation.

9.
J Dairy Sci ; 104(10): 10566-10575, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34334201

RESUMO

Most ß-galactosidases reported are sensitive to the end product (galactose), making it the rate-limiting component for the efficient degradation of lactose through the enzymatic route. Therefore, there is ongoing interest in searching for galactose-tolerant ß-galactosidases. In the present study, the predicted galactose-binding residues of ß-galactosidase from Bacillus coagulans, which were determined by molecular docking, were selected for alanine substitution. The asparagine residue at position 148 (N148) is correlated with the reduction of galactose inhibition. Saturation mutations revealed that the N148C, N148D, N148S, and N148G mutants exhibited weaker galactose inhibition effects. The N148D mutant was used for lactose hydrolysis and exhibited a higher hydrolytic rate. Molecular dynamics revealed that the root mean square deviation and gyration radius of the N148D-galactose complex were higher than those of wild-type enzyme-galactose complex. In addition, the N148D mutant had a higher absolute binding free-energy value. All these factors may lead to a lower affinity between galactose and the mutant enzyme. The use of mutant enzyme may have potential value in lactose hydrolysis.


Assuntos
Bacillus coagulans , Lactose/metabolismo , beta-Galactosidase , Animais , Bacillus coagulans/enzimologia , Hidrólise , Simulação de Acoplamento Molecular , beta-Galactosidase/genética
10.
Science ; 373(6555): 692-696, 2021 08 06.
Artigo em Inglês | MEDLINE | ID: mdl-34353954

RESUMO

Incorporating passive radiative cooling structures into personal thermal management technologies could effectively defend humans against intensifying global climate change. We show that large-scale woven metafabrics can provide high emissivity (94.5%) in the atmospheric window and high reflectivity (92.4%) in the solar spectrum because of the hierarchical-morphology design of the randomly dispersed scatterers throughout the metafabric. Through scalable industrial textile manufacturing routes, our metafabrics exhibit desirable mechanical strength, waterproofness, and breathability for commercial clothing while maintaining efficient radiative cooling ability. Practical application tests demonstrated that a human body covered by our metafabric could be cooled ~4.8°C lower than one covered by commercial cotton fabric. The cost-effectiveness and high performance of our metafabrics present substantial advantages for intelligent garments, smart textiles, and passive radiative cooling applications.

11.
Zool Res ; 42(5): 574-591, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34355876

RESUMO

Amolops chunganensis is a species complex and reported widely from eastern, southern, and southwestern China. Based on molecular data of 19 populations of A. chunganensis sensu lato from China, including the population from Mt. Wuyi (type locality), we recognize A. chunganensis sensu stricto and provide an expanded description based on the topotypic specimens. Combining morphological and molecular data, we describe a new species, Amolops chaochin sp. nov., from southwestern China, which was previously identified as A. chunganensis. The new species is distinguished from all other species in the A. monticola group by: (1) moderate body size, SVL 35.3-39.2 mm in males (n=7), and 50.5-54.4 mm in females (n=7); (2) distinct tympanum, larger than half of eye diameter; (3) small tooth-like projection on anteromedial edge of mandible; (4) circummarginal groove on all fingers; (5) white tubercles on dorsal side of posterior body in both sexes; (6) distinct tubercles on dorsal thigh and white spinose tubercles on dorsal tibia in both sexes; (7) white tubercles on posterior region of tympanum in males; (8) toe webbing reaching disk by dermal fringe on inner side of toe II; (9) vomerine teeth present; (10) transverse bands on dorsal limbs; (11) external vocal sacs present in males. We further reviewed the assignment of Amolops groups, with an overall revision of membership and diagnosis of all species groups.


Assuntos
Anuros/anatomia & histologia , Anuros/classificação , Distribuição Animal , Animais , China , Feminino , Masculino , Filogenia , Especificidade da Espécie
12.
Front Aging Neurosci ; 13: 657095, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34393753

RESUMO

The pathogenesis of Parkinson's disease (PD) is currently unclear. Recent studies have suggested a correlation between vitamin D and PD. Vitamin D and its analogs have protective effects in animal models of PD, but these studies have not clarified the mechanism. Parthanatos is a distinct type of cell death caused by excessive activation of poly (ADP-ribose) polymerase-1 (PARP1), and the activation of PARP1 in PD models suggests that parthanatos may exist in PD pathophysiology. 1,25-Dihydroxyvitamin D3 (calcitriol) is a potential inhibitor of PARP1 in macrophages. This study aimed to investigate whether calcitriol treatment improves PD models and its effects on the parthanatos pathway. A 1-methyl-4-phenylpyridinium (MPP+)-induced cell model and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) subacute animal model were selected as the in vitro and in vivo PD models, and calcitriol was applied in these models. Results showed that parthanatos existed in the MPP+-induced cell model and pretreatment with calcitriol improved cell viability, reduced the excessive activation of PARP1, and relieved parthanatos. The application of calcitriol in the MPTP subacute animal model also improved behavioral tests, restored the damage to dopamine neurons, and reduced the activation of PARP1-related signaling pathways. To verify whether calcitriol interacts with PARP1 through its vitamin D receptor (VDR), siRNA, and overexpression plasmids were used to downregulate or overexpress VDR. Following the downregulation of VDR, the expression and activation of PARP1 increased and PARP1 was inhibited when VDR was overexpressed. Coimmunoprecipitation verified the combination of VDR and PARP1. In short, calcitriol can substantially improve parthanatos in the MPP+-induced cell model and MPTP model, and the protective effect might be partly through the VDR/PARP1 pathway, which provides a new possibility for the treatment of PD.

13.
ACS Nano ; 15(9): 15104-15113, 2021 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-34412474

RESUMO

Alloying-type anode materials are regarded as promising alternatives beyond intercalation-type carbonaceous materials for sodium storage owing to the high specific capacities. The rapid capacity decay arising from the huge volume change during Na+-ion insertion/extraction, however, impedes the practical application. Herein, we report an ultrafine antimony embedded in a porous carbon nanocomposite (Sb@PC) synthesized via facile in situ substitution of the Cu nanoparticles in a metal-organic framework (MOF)-derived octahedron carbon framework for sodium storage. The Sb@PC composite displays an appropriate redox potential (0.5-0.8 V vs Na/Na+) and excellent specific capacities of 634.6, 474.5, and 451.9 mAh g-1 at 0.1, 0.2, and 0.5 A g-1 after 200, 500, and 250 cycles, respectively. Such superior sodium storage performance is primarily ascribed to the MOF-derived three-dimensional porous carbon framework and ultrafine Sb nanoparticles, which not only provides a penetrating network for rapid transfer of charge carriers but also alleviates the agglomeration and volume expansion of Sb during cycling. Ex situ X-ray diffraction and in situ Raman analysis clearly reveal a five-stage reaction mechanism during sodiation and desodiation and demonstrate the excellent reversibility of Sb@PC for sodium storage. Furthermore, post-mortem analysis reveals that the robust structural integrity of Sb@PC can withstand continuous Na+-ion insertion/extraction. This work may provide insight into the effective design of high-capacity alloying-type anode materials for advanced secondary batteries.

14.
Artigo em Inglês | MEDLINE | ID: mdl-34449022

RESUMO

The leakage of chemical compounds in landfill leachate led to serious environment pollution, especially, the compounds termed endocrine disruptors such as bisphenol A (BPA). It is very important to study the adsorption behavior of endocrine disruptors in modified soil for predicting and evaluating the potential harm of endocrine disruptors to the soil. Bentonite-amended Chinese loess mixtures, with various proportions of bentonite, were used for the removal of BPA from an aqueous solution. A batch test was used to investigate the adsorption properties of bisphenol A on bentonite and Chinese loess mixtures. The influences of bentonite proportion, temperature, reaction time, pH, and soil-water ratios on the adsorption process were considered. The Fourier transform infrared spectra (FTIR) was used to clarify the change of functional groups before and after the adsorption of BPA on soil. The adsorption mechanism of BPA on soil was discussed preliminary. The results show that the addition of bentonite to the loess can improve the adsorption rate of BPA. The adsorption of BPA was mainly a spontaneous, exothermic, entropy decreasing physical adsorption process. The interaction between bentonite content and reaction concentration had a beneficial effect on BPA adsorption. The linear relationship between bentonite content and adsorption capacity was obtained. The results indicate that bentonite amended loess can provide a good liner for BPA.

15.
Complement Ther Med ; 59: 102727, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33933577

RESUMO

BACKGROUND: Age-related cognitive decline is a pervasive problem in the ageing population. Baduanjin training is a mind-body exercise with the characteristics of traditional Chinese medicine, and increasing numbers of studies have reported its usefulness in modulating the cognitive performance of various populations. However, no systematic review has evaluated the effect of Baduanjin training on cognition in middle-aged and older adults. OBJECTIVE: To systematically evaluate the effects of Baduanjin on the global cognitive function and specific cognitive domains of middle-aged and elderly people. METHODS: Four literature databases (PubMed, Cochrane library, EMBASE, and Web of Science) and four Chinese databases (Wanfang, China National Knowledge Infrastructure, Chinese Science and Technology Periodical and China Biology Medicine) were searched from inception through May 2020. Randomized controlled trials (RCTs) examining the effect of Baduanjin exercise on the cognitive function of middle-aged and elderly people were included. Assessment of the risk of bias for the included studies and data synthesis were conducted using the software Review Manager 5.3 based on the methods given in the Cochrane Handbook. RESULTS: Baduanjin training showed significant benefit for global cognitive function and parts of specific domains of cognition, including general memory and its sub-domains (i.e., immediate memory and delayed memory), executive function, and processing speed, but no significant difference was found in attention function, visual-spatial ability or long-term memory (a sub-domain of memory). No related adverse events were reported in the included studies. CONCLUSIONS: The findings of this review suggest that Baduanjin is safe and effective in enhancing global cognitive function and memory in middle-aged and older adults and potentially beneficial to parts of the other specific domains of cognition, including executive function and processing speed. However, additional trials with larger sample sizes and a more rigorous design are needed before more definitive conclusions can be drawn.


Assuntos
Disfunção Cognitiva , Qigong , Idoso , Cognição , Exercício Físico , Terapia por Exercício , Humanos , Pessoa de Meia-Idade
16.
Exp Gerontol ; 150: 111396, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-33964318

RESUMO

The purpose of this study was to evaluate the effect of regular resistance training on memory in older adults. METHODS: Eight databases (PubMed, Cochrane Library, EMBASE, Web of Science, SinoMed, China National Knowledge Infrastructure (CNKI), China Science and Technology Periodical Database (VIP) and Wanfang) were searched from their inception to March 24, 2021. The data included in the study were analysed according to the Cochrane handbook using Review Manager 5.3 software. RESULTS: Eighteen eligible randomized controlled trials (RCTs) with a total of 1365 older adults were identified that met the inclusion criteria for the systematic review. Compared with no specific exercise or a low intensity exercise control, regular resistance training significantly improved working memory (standardized mean difference (SMD): 0.27, 95% confidence interval (CI): 0.11, 0.42, P < 0.001), immediate memory (SMD: 0.27, 95% CI: 0.01, 0.54, P = 0.04), and short-term memory (SMD: 0.68, 95% CI: 0.23,1.14, P = 0.003) but had no significant impact on verbal memory (SMD: 0.15, 95% CI: -0.40, 0.71, P = 0.59) or delayed memory (SMD: 0.01, 95% CI: -0.39, 0.42, P = 0.18). CONCLUSIONS: Regular resistance training has a positive beneficial effect on working memory, immediate memory and short-term memory in older adults. However, due to the limitations of the included studies, these findings should be interpreted cautiously.


Assuntos
Treinamento de Força , Idoso , China , Exercício Físico , Humanos , Memória , Ensaios Clínicos Controlados Aleatórios como Assunto
17.
J Comp Physiol B ; 191(4): 793-814, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34002279

RESUMO

To determine that differential bone remodeling mechanism (especially Wnt signaling) in hindlimb unloaded rats and hibernating Daurian ground squirrels, the bone microstructure, mechanical properties, and expression levels of bone remodeling related proteins and key proteins of Wnt/ß-catenin signaling were analyzed in this study. The thickness of cortical and trabecular bone was decreased in femur of hindlimb unloaded rats, while it was maintained in femur of hibernating ground squirrels. Interestingly, the ultimate bending energy and ultimate normalized displacement were reduced and the bending rigidity was increased in tibia of hibernating ground squirrels. Besides, the protein level of Runx2 was decreased in femur and tibia of unloaded rats, while it was maintained in tibia and even increased in femur of hibernating ground squirrels. The protein levels of RANKL and MMP-9 were increased in femur and tibia in unloaded rats, while they were maintained in both femur and tibia of hibernating ground squirrels. The protein level of GSK-3ß was increased in femur and tibia of unloaded rats, while it was maintained in both femur and tibia of hibernating ground squirrels. The phospho-ß-catenin expression was increased in both femur and tibia of unloaded rats, while it was only decreased in femur, but maintained in tibia of hibernating ground squirrels. In conclusion, the femur and tibia in hindlimb unloaded rats showed obvious bone loss, while they mitigated disuse-induced bone loss in hibernating ground squirrels, involving differential protein expression of key molecules in bone remodeling. In comparison with hindlimb unloaded rats, promoting osteoblast differentiation through activating canonical GSK-3ß/ß-catenin signaling involving Runx2 might be an adaptation to natural disuse in femur of hibernating Daurian ground squirrels. However, there was no statistical change in the protein levels of bone formation related proteins, GSK-3ß and phospho-ß-catenin in tibia of hibernating Daurian ground squirrels.


Assuntos
Hibernação , Animais , Remodelação Óssea , Glicogênio Sintase Quinase 3 beta , Membro Posterior , Ratos , Sciuridae
18.
J Ethnopharmacol ; 277: 114223, 2021 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-34044080

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The traditional Chinese medicine (TCM) preparation, Shengmai Yin (SMY), is widely applied in cardiovascular disease treatments. However, the pharmacological mechanism of its therapeutic effects has not been fully clarified. AIM OF THIS STUDY: This study aimed to clearly define the efficacy and underlying mechanism of SMY and its active components in protecting against atherosclerosis. MATERIALS AND METHODS: The pharmacological effects of SMY and its components were evaluated upon a mouse hypercholesteremia model induced by a high cholesterol diet (HCD) for 12 weeks and Apoe-/- mice, a mouse atherosclerosis model. Pathological indicators including serum cholesterol levels, cytokines and histological changes in aortic root plaques were assessed. Untargeted metabolomic, untargeted lipidomic and targeted lipidomic changing profiles were investigated to clarify pharmacological mechanisms. RESULTS: SMY and red ginseng crude extracts (GE) significantly decreased the serum cholesterol levels in hypercholesteremia mice and reduced the aortic root plaque areas and exerted antiatherogenic efficacy in Apoe-/- mice. Moreover, total red ginseng saponin extracts (TGS) showed the most apparent improvement on maintaining lipid homeostasis, representing the effects of red ginseng in SMY on atherosclerosis treatment. Mechanically, TGS inhibited serum secreted phospholipase A2 (sPLA2) activity and lowered the serum levels of lysophosphatidylcholine (lysoPC), which is a risk factor for atherosclerosis. CONCLUSIONS: Our findings revealed that ginsenosides from SMY exerted therapeutic effects on atherosclerosis by maintaining lipid homeostasis including cholesterol and lysoPCs.


Assuntos
Aterosclerose/prevenção & controle , Medicamentos de Ervas Chinesas/farmacologia , Ginsenosídeos/farmacologia , Animais , Apolipoproteínas E/genética , Aterosclerose/genética , Colesterol/sangue , Colesterol na Dieta , Citocinas/sangue , Modelos Animais de Doenças , Combinação de Medicamentos , Ginsenosídeos/isolamento & purificação , Lisofosfatidilcolinas/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout
19.
Brain ; 144(7): 2024-2037, 2021 08 17.
Artigo em Inglês | MEDLINE | ID: mdl-33792662

RESUMO

Increasing evidence suggests that microglial activation is strongly linked to the initiation and progression of Parkinson's disease. Cell-to-cell propagation of α-synuclein pathology is a highlighted feature of Parkinson's disease, and the focus of such research has been primarily on neurons. However, recent studies as well as the data contained herein suggest that microglia, the primary phagocytes in the brain, play a direct role in the spread of α-synuclein pathology. Recent data revealed that plasma exosomes derived from Parkinson's disease patients (PD-EXO) carry pathological α-synuclein and target microglia preferentially. Hence, PD-EXO are likely a key tool for investigating the role of microglia in α-synuclein transmission. We showed that intrastriatal injection of PD-EXO resulted in the propagation of exosomal α-synuclein from microglia to neurons following microglia activation. Toll-like receptor 2 (TLR2) in microglia was activated by exosomal α-synuclein and acted as a crucial mediator of PD-EXO-induced microglial activation. Additionally, partial microglia depletion resulted in a significant decrease of exogenous α-synuclein in the substantia nigra. Furthermore, exosomal α-synuclein internalization was initiated by binding to TLR2 of microglia. Excessive α-synuclein phagocytosis may induce the inflammatory responses of microglia and provide the seed for microglia-to-neuron transmission. Consistently, TLR2 silencing in microglia mitigated α-synuclein pathology in vivo. Overall, the present data support the idea that the interaction of exosomal α-synuclein and microglial TLR2 contribute to excessive α-synuclein phagocytosis and microglial activation, which lead to the further propagation and spread of α-synuclein pathology, thereby highlighting the pivotal roles of reactive microglia in α-synuclein transmission.


Assuntos
Exossomos/metabolismo , Microglia/metabolismo , Doença de Parkinson/metabolismo , Receptor 2 Toll-Like/metabolismo , alfa-Sinucleína/metabolismo , Animais , Encéfalo/metabolismo , Encéfalo/patologia , Feminino , Humanos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Microglia/patologia , Doença de Parkinson/patologia , Ratos , Ratos Sprague-Dawley
20.
Ann Transl Med ; 9(5): 391, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33842612

RESUMO

Background: Head and neck mucosal melanoma (HNMM) is defined as a rare malignant tumor derived from melanocytes. There is no consensus regarding the treatment protocol for HNMM in elderly patients. Methods: The National Cancer Institute's Surveillance, Epidemiology, and End Results database was used to identify elderly patients diagnosed with HNMM from 1975 to 2016. The chi-squared test was used to compare patient characteristics. The reverse Kaplan-Meier method was used to estimate the median follow-up time. The Kaplan-Meier method and log-rank test were used to estimate and compare the overall survival (OS) and disease-specific survival (DSS) of the groups. Cox regression analysis was used to evaluate the risk factors for OS and DSS of HNMM. Results: Our retrospective study included 828 elderly patients with HNMM, and the 5-year OS and DSS rates were 22.4% and 27.4%, respectively. After adjusting for other variables in multivariate analysis, patients undergoing radiotherapy alone had worse OS [hazard ratio (HR) =1.449, 95% confidence interval (CI): 1.010-1.742, P=0.006] and DSS (HR =1.656, 95% CI: 1.257-2.181, P<0.001) than those undergoing surgery alone. No significant difference in OS (HR =0.892, 95% CI: 0.753-1.056, P=0.183) or DSS (HR =0.917, 95% CI: 0.764-1.101, P=0.354) was observed for patients undergoing surgery with or without radiotherapy. Our analysis of the subgroup of patients with complete clinical staging information demonstrated that the effects of surgery alone on OS (HR =0.734, 95% CI: 0.562-0.958, P=0.023) were inferior to those of surgery with radiotherapy, but no significant difference was noted compared with radiotherapy alone. Conclusions: The survival of elderly patients with HNMM is increased with the combination of surgery and radiotherapy compared with surgery alone and radiotherapy alone. In addition, the population-based analysis demonstrated that combination therapy exhibited an obviously increased usage rate from 1975 to 2016, representing a mainstream treatment modality.

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