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1.
Artigo em Inglês | MEDLINE | ID: mdl-38401101

RESUMO

Objective: Maintaining the lower limb in a neutral posture following total knee arthroplasty (TKA) has long been a concept maintained by operators. This study aimed to investigate the relationship between changes in lower limb alignment and the dynamics of knee gait before and after TKA to understand the impact of alignment on gait better and offer a theoretical foundation for correcting lower limb alignment in TKA. Methods: Our study included a group of 20 participants. The cohort consisted of 1 male and 19 females, 11 left and 9 right knees, ages 58 to 81. Using the Opti_Knee® Knee Motion Test System with infrared reflective markers and a high-speed camera, the step length and 6 degrees of freedom of the knee were recorded. Following that, we investigated the association between HKA angle and knee kinematic gait before and after surgery. Results: For preoperative HKA angles ranging from -28° to -3°, we observed increased step length, flexion-extension rotation, and varus-valgus rotation with an increase in HKA angle. Conversely, an increase in HKA angle from -3 ° to 15° corresponded with decreased step length, flexion-extension rotation, and varus-valgus rotation. An increase in HKA angle from 1° to 3° postoperatively increased step length, flexion-extension rotation, and varus-valgus rotation. In contrast, increasing the HKA angle from 3° to 5° resulted in less flexion-extension rotation. The flexion-extension rotation was at its maximum when the HKA angle was 3°. A 3° postoperative varus resulted in improved kinematic gait. Step length, varus-valgus rotation, and flexion-extension rotation increased with increasing HKA angle in the neutral alignment group. In contrast, the non-neutral alignment group exhibited decreased flexion-extension rotation as the HKA angle increased, while step length and varus-valgus rotation increased as the HKA angle increased. The varus-valgus rotation was statistically significant (P < .05) in the preoperative versus early postoperative period in the 6 degrees of freedom. Conclusions: A 3° varus alignment was found to have a superior postoperative knee kinematic gait, implying that a 3° varus alignment may be more suitable as a new gold standard for TKA than the traditional "0°" alignment. The neutral alignment group demonstrated a better knee kinematic gait than the non-neutral alignment group. During early postoperative walking, significant improvements in varus-valgus rotation were found in the 6 degrees of knee freedom.

2.
PLoS One ; 18(12): e0292506, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38096197

RESUMO

BACKGROUND: Individuals with chronic kidney disease (CKD) are at a substantially higher risk for stroke, which may predispose individuals to cognitive impairment. However, the association of low estimated glomerular filtration rate (eGFR) and albuminuria with poorer cognitive performance in patients with stroke is not fully understood, and the current evidence for this association is contradictory. Our aim was to retrospectively investigate whether low eGFR and albuminuria, as indicated by the urine albumin-creatinine ratio (UACR), are independently or jointly associated with worse cognitive performance in patients with ischemic stroke. METHODS: This retrospective study included 608 patients with acute ischemic stroke. Their UACR and eGFR values were obtained from inpatient medical records. Global cognitive function was assessed with the mini-mental state exam (MMSE) and Montreal Cognitive Assessment (MoCA) one month after hospital discharge. The relationship between renal measures and cognitive performance was assessed using univariate and multiple linear regression analyses. Potential confounders included age, gender, BMI, education, diabetes and hypertension history, NIHSS score, smoking and alcohol consumption status, serum total cholesterol, triglyceride, fasting glucose, uric acid, homocysteine, systolic blood pressure, and either eGFR or UACR. RESULTS: Patients had an average age of 66.6±4.1 years, and 48% were females. Average eGFR and UACR were 88.4±12.9 ml/min/1.73m2 and 83.6±314.2 mg/g, respectively. The number of patients with eGFR ≥90, 60-89, and <60 ml/min/1.73 m2 was 371 (61%), 207 (34%), and 30 (5%), respectively, and the percentage of patients with UACR <30 mg/g, 30-300 mg/g, and >300 mg/g was 56%, 39%, and 5%, respectively. Multivariate adjusted models showed that eGFR was independently associated with MMSE (ß = -0.4; 95% CI = -0.5,-0.4; p <0.001) and MoCA (ß = -0.6; 95% CI = -0.7,-0.5; p <0.001). However, UACR was not significantly correlated with MMSE or MoCA. CONCLUSION: In patients with ischemic stroke, reduced eGFR but not albuminuria was associated with lower cognitive performance. These results show that the eGFR decline could be an effective indicator of cognitive impairment after a stroke. Therefore, regular monitoring and early detection of mild renal dysfunction in patients with acute ischemic stroke might be needed.


Assuntos
AVC Isquêmico , Insuficiência Renal Crônica , Acidente Vascular Cerebral , Feminino , Humanos , Pessoa de Meia-Idade , Idoso , Masculino , AVC Isquêmico/complicações , Estudos Retrospectivos , Albuminúria/complicações , Rim , Taxa de Filtração Glomerular/fisiologia , Insuficiência Renal Crônica/complicações , Acidente Vascular Cerebral/complicações , Cognição , Creatinina
3.
Brain Res ; 1810: 148382, 2023 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-37127175

RESUMO

Neuroinflammation plays a crucial role in the development of epilepsy, and suppressing neuroinflammation can delay epileptogenesis. Recent reports have demonstrated that (+)-borneol has neuroprotective effects in several brain disorders by reducing neuroinflammation. However, its effects on epilepsy have not been reported. In this research, we first studied the effect of different doses of (+)-borneol (3, 6, and 12 mg/kg) on neuroinflammation in a pilocarpine model of epileptogenesis by detecting IL-1ß, TNF-α, and COX-2 expression. We demonstrated that different doses of (+)-borneol decreased IL-1ß, TNF-α, and COX-2 levels, with 12 mg/kg having the most substantial effect. Furthermore, we examined the effects of 12 mg/kg (+)-borneol on neuronal damage, glial cell activation, and apoptosis in the hippocampus at different time points (1, 3, and 7 days) after SE. We found that (+)-borneol significantly ameliorated neuronal injury, decreased glial cell activation, and attenuated apoptosis. We also found that (+)-borneol inhibited the NF-κB pathway activation induced by SE. In conclusion, our results indicated that (+)-borneol reduces neuroinflammation by inhibiting the NF-κB pathway activation, exerts neuroprotective effects, and may have an inhibitory effect in epileptogenesis.


Assuntos
Epilepsia , Fármacos Neuroprotetores , Ratos , Animais , NF-kappa B/metabolismo , Pilocarpina/toxicidade , Fármacos Neuroprotetores/farmacologia , Fator de Necrose Tumoral alfa/metabolismo , Doenças Neuroinflamatórias , Ciclo-Oxigenase 2 , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico
4.
Exp Biol Med (Maywood) ; 248(2): 146-156, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36573455

RESUMO

Autophagy plays works by degrading misfolded proteins and dysfunctional organelles and maintains intracellular homeostasis. Apelin-13 has been investigated as an agent that might protect the blood-brain barrier (BBB) from cerebral ischemia/reperfusion (I/R) injury. In this study, we examined whether apelin-13 protects cerebral microvascular endothelial cells, important components of the BBB, from I/R injury by regulating autophagy. To mimic I/R injury, the mouse cerebral microvascular endothelia l cell line bEnd 3 undergoes the process of oxygen and glucose deprivation and re feeding in the process of culture. Cell viability was detected using a commercial kit, and cell migration was monitored by in vitro scratch assay. The tight junction (TJ) proteins ZO-1 and occludin; the autophagy markers LC3 II, beclin 1, and p62; and components of the AKT-mTOR signaling pathway were detected by Western blotting and immunofluorescence. To confirm the role of autophagy in OGD/R and the protective effect of apelin-13, we treated the cells with 3-methyladenine (3-MA), a pharmacological inhibitor of autophagy. Our results demonstrated that OGD/R increased autophagic activity but decreased viability, abundance of TJs, and migration. Viability and TJ abundance were further reduced when the OGD/R group was treated with 3-MA. These results indicated that bEnd.3 upregulates autophagy to ameliorate the effects of OGD/R injury on viability and TJs, but that the autophagy induced by OGD/R alone is not sufficient to protect against the effect on cell migration. Treatment of OGD/R samples with apelin-13 markedly increased viability, TJ abundance, and migration, as well as autophagic activity, whereas 3-MA inhibited this increase, suggesting that apelin-13 exerted its protective effects by upregulating autophagy.


Assuntos
Oxigênio , Traumatismo por Reperfusão , Camundongos , Animais , Oxigênio/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Endoteliais/metabolismo , Glucose/metabolismo , Transdução de Sinais , Serina-Treonina Quinases TOR/metabolismo , Autofagia , Traumatismo por Reperfusão/prevenção & controle , Traumatismo por Reperfusão/metabolismo , Reperfusão
5.
Br J Pharmacol ; 180(5): 573-588, 2023 03.
Artigo em Inglês | MEDLINE | ID: mdl-36464854

RESUMO

An excessive neutrophil count is recognized as a valuable predictor of inflammation and is associated with a higher risk of adverse cardiac events in patients with heart failure. Our understanding of the effectors used by neutrophils to inflict proinflammatory actions needs to be advanced. Recently, emerging evidence has demonstrated a causative role of neutrophil-derived alarmins (i.e. S100A8/A9) in aggravating cardiac injuries by induction of inflammation. In parallel with the neutrophil count, high circulating levels of S100A8/A9 proteins powerfully predict mortality in patients with heart failure. As such, a deeper understanding of the biological functions of neutrophil-derived S100A8/A9 proteins would offer novel therapeutic insights. Here, the basic biology of S100A8/A9 proteins and their pleiotropic roles in cardiovascular diseases are discussed, focusing on heart failure. We also consider the evidence that therapeutic targeting of S100A8/A9 proteins by the humanized vaccine, antibodies or inhibitors is able to town down inflammatory injuries.


Assuntos
Insuficiência Cardíaca , Neutrófilos , Humanos , Neutrófilos/metabolismo , Alarminas/metabolismo , Calgranulina B/metabolismo , Calgranulina A/metabolismo , Insuficiência Cardíaca/tratamento farmacológico , Insuficiência Cardíaca/metabolismo , Inflamação/metabolismo
6.
J Hazard Mater ; 443(Pt B): 130384, 2023 02 05.
Artigo em Inglês | MEDLINE | ID: mdl-36444071

RESUMO

Microplastic (MP) pollution severely impairs the sustainable development of modern agriculture. However, the mechanisms underlying the effects of MP contaminants on nutrient cycles in agroecosystems are poorly understood. In this study, we examined the impacts of two types of MPs, polypropylene (PP) and rubber crumb (RC), on nitrogen (N) transformation and N cycling in soil-peanut system. High concentrations of PP (1% w/w) and RC (1% w/w) inhibited vegetative growth and N uptake in peanut plants by damaging root cells and disturbing soil N cycling. These MPs damaged the plasma membranes of root cells and caused oxidative stress, as evidenced by the decreased number of xylem vessels, which in turn inhibited N uptake by roots. Integrated metagenomic and metabolomic analyses revealed that the differential soil metabolite levels in response to MP treatment affected the microbial community structure in the rhizosphere and the expression of key N cycling-related genes, resulting in altered N transformation and the decreased availability of N in rhizosphere soil. These findings provide the first evidence of the effects of MPs on N uptake in peanut plants and shed light on the importance of rational management of MPs for crop growth and yield in agroecosystems.


Assuntos
Nitrogênio , Solo , Arachis , Plásticos , Microplásticos , Borracha
7.
Am J Transl Res ; 14(10): 7578-7584, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36398262

RESUMO

OBJECTIVE: To analyze the correlation between immunoglobulin M (IgM) against viral capsid antigen (VCA) of Epstein-Barr virus (EBV) and T helper 1 and 2 (Th1/Th2) immunocytokines (ICKs) in children with infectious mononucleosis (IM). METHODS: This is a retrospective study. A total of 40 children with IM treated in our hospital from August 2019 to August 2021 were included in the research group, and another 42 children with upper respiratory tract infection treated during the same period were selected as the control group. The VCA-IgM positive (+) rate and Th1/Th2 ICKs in two groups were detected, and the correlation of VCA-IgM with Th1/Th2 ICKs in IM patients was analyzed. RESULTS: The research group was found to have an evidently higher VCA-IgM+ rate than the control group. Moreover, the accuracy of VCA-IgM in detecting IM was as high as 91.46%. In addition, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), interleukin (IL)-6 and IL-10 presented markedly elevated levels in the research group than in the control group, and in VCA-IgM negative (-) patients compared with VCA-IgM+ patients. There was a positive connection between VCA-IgM and Th1/Th2 ICKs. CONCLUSIONS: IM children showed high VCA-IgM+ rate and imbalance of Th1/Th2 ICKs, and their VCA-IgM and Th1/Th2 ICKs are positively correlated. In addition, VCA-IgM has certain diagnostic value for IM.

8.
Tissue Cell ; 79: 101903, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36081320

RESUMO

OBJECTIVE: Ovarian cancer (OC) is one of the common gynecological malignant tumors. Cell division cycle-associated protein-3 (CDCA3) is involved in the regulation of cell cycle progression. The role of CDCA3 in OC was explored in this study. METHODS: The expression of CDCA3 in OC was evaluated in the Gene Expression Omnibus (GEO) database and further verified by qRT-PCR and Western blot (WB). Subsequently, we established lentivirus-mediated CDCA3 knockdown in OC cell lines HO-8910 and A2780. The biological roles of CDCA3 on proliferation, sensitivity to cisplatin, apoptosis, migration and tumor formation of OC were investigated using loss-of-function assays. RESULTS: CDCA3 was frequently up-regulated in OC. Knockdown of CDAC3 inhibited proliferation and migration, and enhanced apoptosis as well as sensitivity of OC cells to cisplatin. In vivo results further confirmed the inhibitory effect of CDCA3 knockdown on tumor growth. CONCLUSIONS: Our findings indicated that CDCA3 may play an important role in OC progression, and may serve as a potential therapeutic target for the OC treatment.


Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Neoplasias Ovarianas/genética , Cisplatino/farmacologia , Linhagem Celular Tumoral , Carcinoma Epitelial do Ovário , Apoptose/genética , Proteínas de Ciclo Celular/genética , Proliferação de Células/genética , Regulação Neoplásica da Expressão Gênica
9.
Sci Total Environ ; 839: 156367, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35654194

RESUMO

Cr (VI) exists in anion form and can be reduced to positive charged Cr (III) under certain conditions. Can positive charged Cr (III) be continually used for absorbing Cr (VI) to achieve cyclic accumulation of chromium? In this paper, an ion imprinting material for adsorption of Cr (VI) was prepared by dispersing polypyrrole (PPy) in a gelatin/chitosan (Gel/CS) hydrogel network, named Gel/CS/PPy. Based on the conversion of Cr (VI) to Cr (III), a cyclic enrichment process including adsorption-photoreduction-fixation-readsorption of Cr (VI) was established in Gel/CS/PPy hydrogel. The composition and structure of the Gel/CS/PPy were analyzed by scanning electron microscopy (SEM), Fourier transform-infrared spectroscopy (FT-IR), thermogravimetric (TGA), texture analyzer (Universal TA), zeta potential and ultraviolet-visible-near infrared spectra (UV-vis-NIR). The conversion of Cr (VI) and Cr (III) and its promoting effect on readsorption were verified by XPS. The results showed that Gel/CS/PPy has good adsorption capacity for Cr (VI) and excellent photocatalytic ability to reduce Cr (VI) to Cr (III). Cr (III)-loaded Gel/CS/PPy can be further used to adsorb Cr (VI) and showed good adsorption efficiency even after four cycles. The optimal operating condition for Cr (VI) adsorption is pH = 3; 2 g/L dose of Gel/CS/PPy; and the adsorption capacity of Cr (VI) was about 106.8 mg/g after six adsorption cycles. Since Gel/CS/PPy is composed of organic components, high purity chromium can be recovered by simple calcination method later. Therefore, the synthesized Gel/CS/PPy has great potential in the practical application of low concentration Cr (VI) treatment in water.


Assuntos
Quitosana , Poluentes Químicos da Água , Adsorção , Quitosana/química , Cromo/análise , Hidrogéis , Concentração de Íons de Hidrogênio , Cinética , Polímeros/química , Pirróis , Espectroscopia de Infravermelho com Transformada de Fourier , Poluentes Químicos da Água/análise
10.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi ; 36(4): 470-478, 2022 Apr 15.
Artigo em Chinês | MEDLINE | ID: mdl-35426288

RESUMO

Objective: To review the research progress of different cell seeding densities and cell ratios in cartilage tissue engineering. Methods: The literature about tissue engineered cartilage constructed with three-dimensional scaffold was extensively reviewed, and the seeding densities and ratios of most commonly used seed cells were summarized. Results: Articular chondrocytes (ACHs) and bone marrow mesenchymal stem cells (BMSCs) are the most commonly used seed cells, and they can induce hyaline cartilage formation in vitro and in vivo. Cell seeding density and cell ratio both play important roles in cartilage formation. Tissue engineered cartilage with good quality can be produced when the cell seeding density of ACHs or BMSCs reaches or exceeds that in normal articular cartilage. Under the same culture conditions, the ability of pure BMSCs to build hyaline cartilage is weeker than that of pure ACHs or co-culture of both. Conclusion: Due to the effect of scaffold materials, growth factors, and cell passages, optimal cell seeding density and cell ratio need further study.


Assuntos
Cartilagem Articular , Engenharia Tecidual , Células da Medula Óssea , Células Cultivadas , Condrócitos/metabolismo , Condrogênese , Engenharia Tecidual/métodos , Alicerces Teciduais
11.
Colloids Surf B Biointerfaces ; 207: 112004, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-34339971

RESUMO

For minimizing volatilization and leaching of pesticides, and enhancing their residence time on crop surfaces, we synthesized and characterized a novel intelligent pesticide delivery system. Therein, imidacloprid (IMI) was adsorbed by polydopamine modified kaolin (PK) with high adsorption property through hydrogen bonds. Ca-alginate was used as a structural matrix of the system and a protective shell to hinder the pesticide burst release from PK, and endowed the system with unique pH-sensitive property for IMI release. The amino silicone oil (ASO) coating could bind with the waxy layer of crop leaves by the theory of "similarity-intermiscibility", which increased the adhesion of composite on crop leaves. Moreover, by the excellent light-sensitive property of detonation nanodiamond (DND) and temperature-responsive performance of poly(N-isopropylacrylamide) (PNIPAm), the release of IMI from the functional system could be adjusted by sunlight. Besides, the composite displayed high control efficacy. This novel composite can promote the targeting ability and utilization efficiency of pesticides, thus having a huge potential application prospect in agriculture.


Assuntos
Alginatos , Praguicidas , Adsorção , Agricultura , Humanos , Aderências Teciduais
12.
Qual Life Res ; 30(10): 2907-2917, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-33932220

RESUMO

PURPOSE: To investigate the associations between cardiovascular health (CVH) metrics and health-related quality of life (HRQL) among patients with ischemic stroke in China, and further explore the role of physical and cognitive function in their associations. METHODS: This hospital-based study included 1714 patients with first-ever acute ischemic stroke (age ≥ 40 years; 36.7% women) who were admitted to two university hospitals in Shandong, China. We collected information on seven CVH metrics (smoking, body mass index, diet, physical activity, blood pressure, total cholesterol, and fasting blood glucose) through interviews, clinical examinations, and laboratory tests. EQ-5D-3L was used to assess HRQL. Cognitive and physical functioning was assessed by the Montreal Cognitive Assessment test and Barthel index, respectively. Data were analyzed using the general linear regression models. RESULTS: The average score (SD) was 0.746 (0.23) for HRQL index and 72.7 (15.8) for self-rated health. Optimal levels of four individual CVH metric components (diet, physical activity, blood pressure, and blood glucose) and a higher composite CVH score were significantly associated with a greater HRQL index and better self-rated health (p < 0.05 for all). Physical dependence and cognitive impairment were associated with a lower HRQL index and poorer self-rated health status (p < 0.001). Furthermore, the relationships between CVH metrics and HRQL index varied by functional status, such that their associations were statistically significant only among people who had physical dependence or cognitive impairment. CONCLUSION: Achieving a better cardiovascular health profile is associated with better quality of life among ischemic stroke survivors, primarily in those with physical or cognitive impairment.


Assuntos
Isquemia Encefálica , Doenças Cardiovasculares , AVC Isquêmico , Acidente Vascular Cerebral , Adulto , Isquemia Encefálica/epidemiologia , Doenças Cardiovasculares/epidemiologia , Feminino , Nível de Saúde , Humanos , Masculino , Indicadores de Qualidade em Assistência à Saúde , Qualidade de Vida/psicologia , Fatores de Risco , Acidente Vascular Cerebral/epidemiologia
13.
Front Pharmacol ; 12: 622262, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33584319

RESUMO

It has become widely accepted that inflammation is a driving force behind a variety of chronic diseases, such as cardiovascular disease, diabetes, kidney disease, cancer, neurodegenerative disorders, etc. However, the existing nonsteroidal anti-inflammatory drugs show a limited utility in clinical patients. Therefore, the novel agents with different inflammation-inhibitory mechanisms are worth pursuing. Metformin, a synthetic derivative of guanidine, has a history of more than 50 years of clinical experience in treating patients with type 2 diabetes. Intense research efforts have been dedicated to proving metformin's inflammation-inhibitory effects in cells, animal models, patient records, and randomized clinical trials. The emerging evidence also indicates its therapeutic potential in clinical domains other than type 2 diabetes. Herein, this article appraises current pre-clinical and clinical findings, emphasizing metformin's anti-inflammatory properties under individual pathophysiological scenarios. In summary, the anti-inflammatory effects of metformin are evident in pre-clinical models. By comparison, there are still clinical perplexities to be addressed in repurposing metformin to inflammation-driven chronic diseases. Future randomized controlled trials, incorporating better stratification/targeting, would establish metformin's utility in this clinical setting.

14.
Mol Med Rep ; 23(4)2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33576438

RESUMO

Malignant tumors of the central nervous system (CNS) are among the types of cancer with the poorest prognosis and glioma is the commonest primary CNS tumor. A mitochondrial DNA (mtDNA)­depleted cell line C6ρ0 was generated from C6 glioma cells after long­term exposure to ethidium bromide and 2',3'­dideoxycytidine in order to determine the effect of mtDNA damage on cell proliferation and pathological changes in glioma cells. Single cell clones were isolated and identified after 42 days of incubation. Repopulated cybrids were formed when the clonal C6ρ0 cells were fused with rat platelets and no difference was observed in their growth in a selective medium without uridine and pyruvate compared with the growth of the parent C6 cells. Disruption of mtDNA resulted in changes in mitochondrial morphology, decreased cell proliferation, reduced intracellular reactive oxygen species and intracellular ATP, along with decreased mtDNA and mitochondrial membrane potential in C6ρ0 cells compared with the C6 cells. Taken together, C6ρ0 cells without mtDNA were established for the first time and their characteristics were compared with parent cells. This C6ρ0 cell line could be used to explore the contribution of mitochondrial dysfunction and mtDNA mutations in the pathogenesis of glioma.


Assuntos
Neoplasias Encefálicas/genética , DNA Mitocondrial/genética , Glioma/genética , Mitocôndrias/genética , Trifosfato de Adenosina/metabolismo , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias Encefálicas/patologia , Linhagem Celular Tumoral , Proliferação de Células/genética , DNA Mitocondrial/metabolismo , Glioma/metabolismo , Glioma/patologia , Espaço Intracelular/metabolismo , Potencial da Membrana Mitocondrial/genética , Potencial da Membrana Mitocondrial/fisiologia , Mitocôndrias/metabolismo , Ratos , Espécies Reativas de Oxigênio/metabolismo
15.
Nutr Metab Cardiovasc Dis ; 31(1): 333-343, 2021 01 04.
Artigo em Inglês | MEDLINE | ID: mdl-33500109

RESUMO

BACKGROUND AND AIMS: Diabetes is one of the most important risk factors and comorbidities of ischemic stroke. Endoplasmic reticulum stress (ERS) is considered to be the major injury mechanism of ischemic stroke with diabetes. Studies have found that incretin can inhibit ERS in ischemia-reperfusion injury of the liver and heart. We aimed to explore the effects of GLP-1/GIP double agonist DA3-CH and GLP-1 single agonist liraglutide on ERS and apoptosis in diabetic rats with cerebral ischemia-reperfusion injury. METHODS AND RESULTS: 72 Sprague-Dawley (SD) male rats were randomly divided into 4 groups: ① blank group (Sham group, n = 18); model group (Saline group, n = 18); DA3 treatment group (DA3 group, n = 18); liraglutide treatment group (Lir group, n = 18). The Sham group was not given any treatment and was only raised in the same environment as the other groups. The remaining 3 groups used STZ-induced diabetes models. After the successful membrane formation of diabetes, DA3-CH and liraglutide (10 mmol/kg, once-daily for 14 days) were injected intraperitoneally. Thereafter, rats were subjected to middle cerebral artery occlusion followed by 24-h reperfusion. Animals were evaluated for neurologic deficit score, infarct volume, and biomarker analyses of the brain after ischemia. The DA3-CH-treated and liraglutide-treated groups showed significantly reduced scores of neurological dysfunction and cerebral infarction size, and reduced the expression of ERS markers GRP78, CHOP and Caspase-12, and the expression of apoptosis marker bax. Anti-apoptotic markers bcl-2 and neuronal numbers increased significantly. CONCLUSIONS: DA3-CH and liraglutide have obvious neuroprotective effects in a rat model of cerebral ischemia-reperfusion injury with diabetes, which can reduce the infarct size and the neurological deficit score. Their exert neuroprotective effects in a rat model of cerebral ischemia-reperfusion injury with diabetes by inhibiting endoplasmic reticulum stress and thereby reducing apoptosis. DA3 is better than liraglutide.


Assuntos
Encéfalo/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Incretinas/farmacologia , Infarto da Artéria Cerebral Média/tratamento farmacológico , Liraglutida/farmacologia , Peptídeos/farmacologia , Traumatismo por Reperfusão/prevenção & controle , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/metabolismo , Encéfalo/metabolismo , Encéfalo/patologia , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Experimental/patologia , Chaperona BiP do Retículo Endoplasmático , Receptor do Peptídeo Semelhante ao Glucagon 1/agonistas , Receptor do Peptídeo Semelhante ao Glucagon 1/metabolismo , Humanos , Infarto da Artéria Cerebral Média/metabolismo , Infarto da Artéria Cerebral Média/patologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/patologia , Ratos Sprague-Dawley , Receptores dos Hormônios Gastrointestinais/agonistas , Receptores dos Hormônios Gastrointestinais/metabolismo , Traumatismo por Reperfusão/metabolismo , Traumatismo por Reperfusão/patologia , Transdução de Sinais , Estreptozocina
16.
J Biomater Appl ; 35(7): 814-822, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32777971

RESUMO

Critical size bone defects are one of the most serious complications in orthopedics due to the lack of effective osteogenesis treatment. We fabricated carboxymethyl cellulose with phenol moieties (CMC-ph) microcapsules loaded with gene-modified rat bone mesenchymal stem cells (rBMSCs) that secrete hBMP2 following doxycycline (DOX) induction. The results showed that the morphology of microcapsules was spherical, and their diameters have equally distributed in the range of 100-150 µm; the viability of rBMSCs was unchanged over time. Through real-time PCR and Western blot analyses, the rBMSCs in microcapsules were found to secrete hBMP2 and to have upregulated mRNA and protein expression of osteogenesis-related genes in vitro and in vivo. Furthermore, the in vivo results suggested that the group with the middle concentration of cells expressed the highest amount of osteogenic protein over time. In this study, we showed that gene-modified rBMSCs in CMC-ph microcapsules had good morphology and viability. The BMP2-BMSCs/CMC-Ph microcapsule system could upregulate osteogenic mRNA and protein in vitro and in vivo. Further analysis demonstrated that the medium concentration of cells had a suitable density for transplantation in nude mice. Therefore, BMP2-BMSCs/CMC-Ph microcapsule constructs have potential for bone regeneration in vivo.


Assuntos
Carboximetilcelulose Sódica/química , Células-Tronco Mesenquimais/citologia , Osteogênese , Engenharia Tecidual/métodos , Animais , Proteína Morfogenética Óssea 2/metabolismo , Regeneração Óssea/efeitos dos fármacos , Cápsulas , Diferenciação Celular/efeitos dos fármacos , Sobrevivência Celular , Doxiciclina , Feminino , Fêmur/metabolismo , Humanos , Técnicas In Vitro , Masculino , Camundongos , Camundongos Nus , Microfluídica , Fenol/química , Polímeros/química , RNA Mensageiro/metabolismo , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real
17.
Comput Methods Programs Biomed ; 198: 105775, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33130494

RESUMO

BACKGROUND AND OBJECTIVES: To compare mechanical properties of femoral tumor treatments so that better operative strategy for limb tumors surgery is optimized. METHODS: Fourteen femoral CT images were randomly selected to rebuild 3D models by MIMICS. They were then executed by reverse engineering softwares for simulative modes. Mode #1: Intralesional curettage with cement filled plus fixator; Mode #2: Distal femur resection with tumorous prosthesis replaced. Finally, the mechanical aspects such as stress and displacement were compared by finite element analysis. RESULTS: Analyzed by AnSys, the observation indexes were measured as follows: for displacement of femurs, d=1.4762 (< a=3.9042 < c=3.9845 < b=4.1159) in mm is the most staple of all models; for displacement of implants (fixators or prostheses), it's similar to the behavior of femurs and with no significant difference; for stresses of femurs, no significant difference was found among all models; the stresses of implants (fixations and prostheses) were observed as d=39.6334 (< a=58.6206 < c=61.8150 < b=62.6626) in MPa correspondently, which is the least; for stresses of the general system, the average of peak values for integrated devices of all models are: d=40.8072 (< a=58.6206 < c=61.7831< b=62.6626) in MPa, which is also the least. As a final result, both maximum values for displacement and stress of mode 2 are lower than those of mode 1. CONCLUSIONS: Our finite element analysis of limb salvage simulation in biomechanics proved that, to treat distal femoral bone tumors, prosthetic replacement is more efficient than intralesional curettage.


Assuntos
Neoplasias Ósseas , Salvamento de Membro , Fenômenos Biomecânicos , Neoplasias Ósseas/diagnóstico por imagem , Neoplasias Ósseas/cirurgia , Curetagem , Análise de Elementos Finitos , Humanos , Estresse Mecânico
18.
J Invest Surg ; 33(5): 428-437, 2020 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30516078

RESUMO

Background: Little is known about how biomechanics govern the five fixtures such as DHS, MLS, DHS + LS, LP, and HA are accepted as common therapeutic techniques. Aims and objectives: A series of numerical models for a femoral neck fracture of Pauwels-I will be constructed by innovative approach of finite element in order to determine the most optimized option in comparison with biomechanical performance. Method: Twenty sets of computer tomography scanned femora were imported onto Mimics to extract 3 D models; these specimens were transferred to Geomagic-Studio for a simulative osteotomy and kyrtograph; then, they underwent UG to fit simulative solid models; 5 sorts of fixture were then expressed by Pro-Engineer virtually. After processing with HyperMesh, all compartments (fracture model + internal implant) were assembled onto 5 systems: "Dynamic Hip Screw (DHS), Multiple Lag screw (MLS), DHS + LS, femoral Locking Plate (LP) and HemiArthroplasty (HA)." Eventually, numerical models of the finite-elemental analysis were exported to AnSys to determine the solution. Result: Four models of fixation and a simulation of HA for Pauwels-I were established, validated, and analyzed with the following findings: In term of displacement, these 5 fixtures ranged between 0.3801 and 0.7536 mm have no significant difference; in term of stress, the averages of peaks for integral assemblage are b(MLS) = 43.5766 ≈< d(LP) = 43.6657 ≈< e(Ha) = 43.6657 < c(DHS + LS) = 66.5494 < a(DHS) = 105.617 in MPa indicate that MLS, LP and HA are not significantly different, but less than DHS + LS or DHS in each. Conclusion: A fixture of MLS or LP with optional HA should be recommended to clinically optimize a Pauwels-I facture.


Assuntos
Fraturas do Colo Femoral/cirurgia , Fixação Interna de Fraturas/métodos , Hemiartroplastia/métodos , Modelos Biológicos , Osteotomia/métodos , Adulto , Fenômenos Biomecânicos , Placas Ósseas , Parafusos Ósseos , Módulo de Elasticidade , Fraturas do Colo Femoral/classificação , Fraturas do Colo Femoral/diagnóstico , Fêmur/diagnóstico por imagem , Fêmur/lesões , Fêmur/cirurgia , Análise de Elementos Finitos , Fixação Interna de Fraturas/instrumentação , Hemiartroplastia/instrumentação , Prótese de Quadril , Humanos , Imageamento Tridimensional , Teste de Materiais , Osteotomia/instrumentação , Desenho de Prótese , Tomografia Computadorizada por Raios X
19.
Plant Sci ; 284: 192-202, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31084872

RESUMO

In rice, OsBBX14, a B-box (BBX) transcription factor, reportedly delays heading. Here, we revealed that OsBBX14 positively regulates rice photomorphogenesis. The OsBBX14-overexpressing (OsBBX14-OX) seedlings were hypersensitive to light, especially blue light, and exhibited dwarfism, while the OsBBX14 knock-out plants (osbbx14) were taller than wild-type plants under blue light. Histological analyses indicated that the observed dwarfism was mainly due to decreased cell length. Additionally, OsBBX14 abundance (mRNA and protein levels) was influenced by different light wavelengths in a time-dependent manner. The expression levels of HY5Ls (LONG HYPOCOTYL 5 LIKE) and ELIPs (EARLY LIGHT-INDUCIBLE PROTEIN) genes, whose Arabidopsis thaliana homologs function as positive regulators in the light signaling pathway, were significantly upregulated in OsBBX14-OX lines. In contrast, the expression of genes related to cell wall organization and dwarfism was downregulated in OsBBX14-OX lines. Chromatin immunoprecipitation (ChIP) assays confirmed that OsBBX14 binds to the T/G-box of HY5L1 (LONG HYPOCOTYL 5 LIKE 1) promoter. LUC complementation imaging (LCI) results suggested that OsBBX14 had physical interaction with OsCRY2 protein. Collectively, in response to blue light, OsBBX14 promotes photomorphogenesis, probably by directly or indirectly regulating the expression of HY5L1 or other genes related to cell wall organization and dwarfism.


Assuntos
Oryza/metabolismo , Proteínas de Plantas/metabolismo , Western Blotting , Imunoprecipitação da Cromatina , Regulação da Expressão Gênica de Plantas/efeitos da radiação , Luz , Oryza/crescimento & desenvolvimento , Plantas Geneticamente Modificadas , Reação em Cadeia da Polimerase em Tempo Real , Nicotiana , Técnicas do Sistema de Duplo-Híbrido
20.
Life Sci ; 224: 95-108, 2019 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-30905782

RESUMO

AIMS: Parkinson's disease (PD) is a common neurodegenerative disease typically associated with the accumulation of α-synuclein. Autophagy impairment is thought to be involved in the dopaminergic neurodegeneration in PD. We investigate the effect of Apelin-36 on the activated phosphatidylinositol 3-kinase (PI3K)/protein kinase B(Akt)/the mammalian target of rapamycin (mTOR) autophagy pathway in 1-methyl-4-phenylpyridinium (MPP+)-treated SH-SY5Y cells, which is involved in the cytoprotective effect of Apelin-36. MAIN METHODS: SH-SY5Y cells were treated with 1-Methyl-4-phenylpyridine (MPP+) with or without Apelin-36. The cell viability, apoptotic ratio, the form of autophagic vacuoles, the expression of tyrosine hydroxylase (TH), α-synuclein, phosphorylation of PI3K, AKT, mTOR, microtubule-associated protein 1 Light Chain 3 II/I (LC3II/I) and p62 were detected to investigate the neuroprotective effect of Apelin-36. KEY FINDINGS: The results indicate that Apelin-36 significantly improved the cell viability and decreased the apoptosis in MPP+-treated SH-SY5Y cells. The decreased expression of tyrosine hydroxylase (TH) induced by MPP+ was significantly increased by Apelin36 pretreatment. Moreover, Apelin36 significantly increased the autophagic vacuoles. The ratio of LC3II/I was significantly increased by Apelin36, as well as the decreased p62 expression. In addition, the activated PI3K/AKT/mTOR pathway induced by MPP+ was significantly inhibited by Apelin36. Additionally, Apelin36 significantly decreased the α-synuclein expression. Furthermore, the cytoprotective effect of Apelin-36 was weakened by pretreatment with Insulin-like Growth Factor-1 (IGF-1), an activator of PI3K/Akt, and MHY1485, an mTOR activator. SIGNIFICANCE: Our results demonstrated that Apelin-36 protects against MPP+-induced cytotoxicity through PI3K/Akt/mTOR autophagy pathway in PD model in vitro, which provides a new theoretical basis for the treatment of PD.


Assuntos
1-Metil-4-fenilpiridínio/efeitos adversos , Apelina/metabolismo , Neuroblastoma/prevenção & controle , Fármacos Neuroprotetores/farmacologia , Fosfatidilinositol 3-Quinase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Apelina/genética , Apoptose , Autofagia , Humanos , Neuroblastoma/induzido quimicamente , Neuroblastoma/metabolismo , Neuroblastoma/patologia , Fosfatidilinositol 3-Quinase/genética , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , Transdução de Sinais , Serina-Treonina Quinases TOR/genética , Células Tumorais Cultivadas
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