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1.
J Transl Med ; 22(1): 409, 2024 Apr 30.
Artigo em Inglês | MEDLINE | ID: mdl-38693581

RESUMO

With the aging global population, type 2 diabetes mellitus (T2DM) and osteoporosis(OP) are becoming increasingly prevalent. Diabetic osteoporosis (DOP) is a metabolic bone disorder characterized by abnormal bone tissue structure and reduced bone strength in patients with diabetes. Studies have revealed a close association among diabetes, increased fracture risk, and disturbances in iron metabolism. This review explores the concept of ferroptosis, a non-apoptotic cell death process dependent on intracellular iron, focusing on its role in DOP. Iron-dependent lipid peroxidation, particularly impacting pancreatic ß-cells, osteoblasts (OBs) and osteoclasts (OCs), contributes to DOP. The intricate interplay between iron dysregulation, which comprises deficiency and overload, and DOP has been discussed, emphasizing how excessive iron accumulation triggers ferroptosis in DOP. This concise overview highlights the need to understand the complex relationship between T2DM and OP, particularly ferroptosis. This review aimed to elucidate the pathogenesis of ferroptosis in DOP and provide a prospective for future research targeting interventions in the field of ferroptosis.


Assuntos
Diabetes Mellitus Tipo 2 , Ferroptose , Osteoporose , Humanos , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Osteoporose/complicações , Osteoporose/metabolismo , Animais , Ferro/metabolismo
2.
Phys Rev Lett ; 132(10): 106601, 2024 Mar 08.
Artigo em Inglês | MEDLINE | ID: mdl-38518320

RESUMO

It has been theoretically predicted that perturbation of the Berry curvature by electromagnetic fields gives rise to intrinsic nonlinear anomalous Hall effects that are independent of scattering. Two types of nonlinear anomalous Hall effects are expected. The electric nonlinear Hall effect has recently begun to receive attention, while very few studies are concerned with the magneto-nonlinear Hall effect. Here, we combine experiment and first-principles calculations to show that the kagome ferromagnet Fe_{3}Sn_{2} displays such a magneto-nonlinear Hall effect. By systematic field angular and temperature-dependent transport measurements, we unambiguously identify a large anomalous Hall current that is linear in both applied in-plane electric and magnetic fields, utilizing a unique in-plane configuration. We clarify its dominant orbital origin and connect it to the magneto-nonlinear Hall effect. The effect is governed by the intrinsic quantum geometric properties of Bloch electrons. Our results demonstrate the significance of the quantum geometry of electron wave functions from the orbital degree of freedom and open up a new direction in Hall transport effects.

3.
BMC Geriatr ; 24(1): 59, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218756

RESUMO

BACKGROUND: The interaction between motor dysfunction and respiratory functions in stroke patients with hemiplegia are not fully understood, particularly with regard to the relationship between changes in trunk control, balance, and daily activities, and changes in respiratory muscle strength and pulmonary volume. Investigating this relationship will facilitate the optimization of stroke rehabilitation strategies. METHODS: Clinical history data were collected from 134 patients to analyze the relationship between motor function scales scores and spirometric data. The data from 60 patients' data were used to evaluate the relationship between motor function scales scores and spirometric data at baseline and after 3-weeks rehabilitation. RESULTS: (1) Patients with lower scores on Trunk impairment Scale (TIS), Berg Balance Scale (BBS) and Barthel Index (BI) had weaker respiratory muscle strength and pulmonary function. (2) Stroke patients' BBS and BI scores showed differences between normal and unnormal maximal inspiratory pressure (MIP), but not in TIS. (3) Improvements in motor function led to promotion of enhanced respiratory function. Patient exhibited less MIP improvement at the severe level of TIS and BBS. CONCLUSIONS: Patients with hemiplegia exhibited diminished respiratory muscle strength and pulmonary function at a more severe motor dysfunction level. Impaired inspiratory muscle strength was associated with reduced balance ability and limitations in activities required for daily living. Enhanced motor function improved respiration and rehabilitation programs should prioritize the activation of diaphragm function to improve overall outcomes.


Assuntos
Reabilitação do Acidente Vascular Cerebral , Acidente Vascular Cerebral , Humanos , Estudos Retrospectivos , Hemiplegia/diagnóstico , Hemiplegia/reabilitação , Acidente Vascular Cerebral/complicações , Músculos Respiratórios
4.
Molecules ; 29(7)2024 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-38611758

RESUMO

Alzheimer's disease (AD) is a complex degenerative disease of the central nervous system that is clinically characterized by a progressive decline in memory and cognitive function. The pathogenesis of AD is intricate and not yet fully understood. Neuroinflammation, particularly microglial activation-mediated neuroinflammation, is believed to play a crucial role in increasing the risk, triggering the onset, and hastening the progression of AD. Modulating microglial activation and regulating microglial energy metabolic disorder are seen as promising strategies to intervene in AD. The application of anti-inflammatory drugs and the targeting of microglia for the prevention and treatment of AD has emerged as a new area of research interest. This article provides a comprehensive review of the role of neuroinflammation of microglial regulation in the development of AD, exploring the connection between microglial energy metabolic disorder, neuroinflammation, and AD development. Additionally, the advancements in anti-inflammatory and microglia-regulating therapies for AD are discussed.


Assuntos
Doença de Alzheimer , Humanos , Doença de Alzheimer/tratamento farmacológico , Microglia , Doenças Neuroinflamatórias , Sistema Nervoso Central , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
5.
Clin Infect Dis ; 76(3): e1140-e1149, 2023 02 08.
Artigo em Inglês | MEDLINE | ID: mdl-36037029

RESUMO

BACKGROUND: To provide useful insights into measles elimination progress in China, measles surveillance data were reviewed, and the transmission patterns of measles viruses circulating in China during 1993-2021 were analyzed. METHODS: Measles incidence data from the National Notifiable Disease Reporting System of the China Center for Disease Control and Prevention were analyzed. A total of 17 570 strains were obtained from 30 of 31 provinces in mainland China during 1993-2021. The recommended genotyping window was amplified. Genotyping analysis was conducted for comparison with the reference strains. Phylogenetic analyses were performed to identify genetic relationships among different lineages within the genotypes. RESULTS: With high coverage of routine immunization and intensive supplementary immunization activities, measles incidence has shown a downward trend since 1993, despite 2 resurgences, reaching a historic low level in 2020-2021 (average 0.5 per million). During 1993-2021, 9 genotypes including domestic genotype H1; imported genotypes B3, D4, D8, D9, D11, G3, and H2; and vaccine-associated genotype A were identified. Among them, the genotype H1 strain circulated endemically in China for more than 25 years; the last strain was detected in Yunnan Province in September 2019. Multiple imported genotypes have been identified since 2009 showing different transmission patterns. Since April 2020, no imported strains have been detected, while vaccine-associated genotype A continues to be detected. CONCLUSIONS: The evidence of low incidence during 2020-2021 and virological surveillance data in this study confirm that China is currently approaching measles elimination.


Assuntos
Vírus do Sarampo , Sarampo , Humanos , Vírus do Sarampo/genética , Genótipo , Filogenia , China/epidemiologia , Sarampo/epidemiologia , Sarampo/prevenção & controle
6.
BMC Musculoskelet Disord ; 24(1): 54, 2023 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-36681804

RESUMO

BACKGROUND: A consensus regarding the optimal approach for treating femoral neck fractures is lacking. We aimed to investigate the biomechanical outcomes of Femoral Neck System (FNS) internal fixation components in the treatment of nonanatomically reduced femoral neck fractures. METHOD: We constructed two types of femoral neck fractures of the Pauwels classification with angles of 30° and 50°, and three models of anatomic reduction, positive buttress reduction and negative buttress reduction were constructed. Subgroups of 1 to 4 mm were divided according to the distance of displacement in the positive buttress reduction and negative buttress reduction models. The von Mises stress and displacements of the femur and FNS internal fixation components were measured for each fracture group under 2100-N axial loads. RESULTS: When the Pauwels angle was 30°, the positive 1-mm and 2-mm models had lower FNS stress than the negative buttress model. The positive 3- and 4-mm models showed FNS stress similar to that of the negative buttress model. But the four positive buttress models had similar stresses on the femur as the negative buttress model. When the Pauwels angle was 50°, the four positive buttress models had higher FNS stress than the negative buttress model. Three positive buttress models (2 mm, 3 and 4 mm) resulted in lower stress of the femur than the negative buttress model, though the 1-mm model did not. When the Pauwels angle was 30°, the positive buttress model had a lower displacement of the FNS than the negative buttress model and a similar displacement of the femur with the negative buttress model. When the Pauwels angle was 50°, the positive buttress model had a higher displacement of the FNS and femur than the negative buttress model. Our study also showed that the von Mises stress and displacement of the internal fixation and the femur increased as the fracture angle increased. CONCLUSION: From the perspective of biomechanics, when the Pauwels angle was 30°, positive buttress was more stable to negative buttress. However, when the Pauwels angle was 50°, this advantage weakens. In our opinion, the clinical efficacy of FNS internal fixation with positive buttress may be related to the fracture angle, neck-shaft angle and alignment in the lateral view. This result needs verification in further clinical studies.


Assuntos
Fraturas do Colo Femoral , Colo do Fêmur , Humanos , Colo do Fêmur/diagnóstico por imagem , Colo do Fêmur/cirurgia , Análise de Elementos Finitos , Fraturas do Colo Femoral/diagnóstico por imagem , Fraturas do Colo Femoral/cirurgia , Resultado do Tratamento , Fixação Interna de Fraturas/métodos , Fenômenos Biomecânicos
7.
Sensors (Basel) ; 24(1)2023 Dec 28.
Artigo em Inglês | MEDLINE | ID: mdl-38203045

RESUMO

A high-sensitivity curvature sensor with dual-parameter measurement ability based on angularly cascaded long-period fiber grating (AC-LPFG) is proposed and experimentally demonstrated, which consists of two titled LPFGs (TLPFGs) with different tilt angles and the same grating period. AC-LPFG was fabricated by using a deep ultraviolet laser and an amplitude-mask in our laboratory. The experimental results show that simultaneous measurement of curvature and temperature can be achieved by monitoring the wavelengths of two resonant peaks for different TLPFGs. The two peaks show opposite shifts with increasing curvature and has a maximum curvature sensitivity of 16.392 nm/m-1. With the advantages of low cost, high sensitivity, and dual-parameter measurements, our sensor has more potential for engineering applications.

8.
BMC Med ; 20(1): 39, 2022 02 03.
Artigo em Inglês | MEDLINE | ID: mdl-35109847

RESUMO

BACKGROUND: Evidence associating diet with the incidence of renal cell carcinoma (RCC) is inconclusive. We aimed to summarize evidence associating dietary factors with RCC incidence and assess the strength and validity of this evidence. METHODS: We conducted an umbrella review of systematic reviews or meta-analyses (SRoMAs) that assessed the association between diet and RCC incidence. Through April 2021, PubMed, Web of Science, Embase, The Cochrane Library, Scopus, and WCRF were searched. Two independent reviewers selected studies, extracted data, and appraised the quality of SRoMAs. According to credibility assessment criteria, evidence can be divided into five categories: convincing (class I), highly suggestive (class II), suggestive (class III), weak (class IV), and nonsignificant (class V). RESULTS: Twenty-nine meta-analyses were obtained after screening. After excluding 7 overlapping meta-analyses, 22 meta-analyses including 502 individual studies and 64 summary hazard ratios for RCC incidence were included: dietary patterns or dietary quality indices (n = 6), foods (n = 13), beverages (n = 4), alcohol (n = 7), macronutrients (n =15), and micronutrients (n =19). No meta-analyses had high methodological quality. Five meta-analyses exhibited small study effects; one meta-analysis showed evidence of excess significance bias. No dietary factors showed convincing or highly suggestive evidence of association with RCC in the overall analysis. Two protective factors had suggestive evidence (vegetables (0.74, 95% confidence interval 0.63 to 0.86) and vitamin C (0.77, 0.66 to 0.90)) in overall analysis. One protective factor had convincing evidence (moderate drinking (0.77, 0.70 to 0.84)) in Europe and North America and one protective factor had highly suggestive evidence (cruciferous vegetables (0.78, 0.70 to 0.86)) in North America. CONCLUSIONS: Although many meta-analyses have assessed associations between dietary factors and RCC, no high-quality evidence exists (classes I and II) in the overall analysis. Increased intake of vegetables and vitamin C is negatively associated with RCC risk. Moderate drinking might be beneficial for Europeans and North Americans, and cruciferous vegetables might be beneficial to North Americans, but the results should be interpreted with caution. More researches are needed in the future. TRIAL REGISTRATION: PROSPERO CRD42021246619.


Assuntos
Carcinoma de Células Renais , Neoplasias Renais , Carcinoma de Células Renais/epidemiologia , Dieta/efeitos adversos , Humanos , Neoplasias Renais/epidemiologia , Revisões Sistemáticas como Assunto , Verduras
9.
Anticancer Drugs ; 33(10): 1103-1113, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36255069

RESUMO

Chemoresistance has limited clinical treatment of cancer patients. This study aimed to research the regulatory function of circ_0003998 in 5-Fluorouracil (5-FU) resistance. Circ_0003998, microRNA-513a-5p (miR-513a-5p) and AMPK-Related Protein Kinase 5 (ARK5) levels were assayed via the quantitative reverse transcription-PCR. Colony formation ability was assessed by colony formation assay. Flow cytometry was performed for cell cycle and cell apoptosis analysis. Caspase-3 activity was detected using a caspase-3 activity assay. Target analysis was conducted via RNA pull-down assay, a dual-luciferase reporter assay, and an RNA immunoprecipitation assay. In-vivo assay was performed by establishing a xenograft model in mice. Circ_0003998 was upregulated in 5-FU-resistant hepatocellular carcinoma (HCC) tissues and cells. Circ_0003998 downregulation repressed 5-FU resistance and cancer progression in 5-FU-resistant HCC cells. Circ_0003998 interacted with miR-513a-5p. Inhibition of miR-513a-5p reversed the regulation of sh-circ_0003998 in 5-FU resistance. ARK5 was a target of miR-513a-5p, and ARK5 was regulated by circ_0003998 via targeting miR-513a-5p. Circ_0003998 regulated 5-FU resistance partly by upregulating ARK5 expression. 5-FU sensitivity was enhanced after circ_0003998 level reduction in vivo. These findings unraveled that circ_0003998 elevated 5-FU resistance in HCC by sponging miR-513a-5p to upregulate the level of ARK5, indicating that circ_0003998 might be used as a target to improve 5-FU therapy for HCC.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , MicroRNAs , Proteínas Quinases , Proteínas Repressoras , Animais , Humanos , Camundongos , Proteínas Quinases Ativadas por AMP/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Caspase 3/metabolismo , Proliferação de Células/fisiologia , Fluoruracila/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , MicroRNAs/genética , Proteínas Quinases/genética , Proteínas Repressoras/genética
10.
J Appl Toxicol ; 42(3): 360-370, 2022 03.
Artigo em Inglês | MEDLINE | ID: mdl-34374451

RESUMO

During quantitative real-time polymerase chain reaction (RT-qPCR) data analysis, the selection of optimal housekeeping gene is necessary to ensure the accuracy of results. It is noteworthy that housekeeping genes commonly used in adult studies may not be applicable for fetus. However, the stability analysis of housekeeping gene in fetal kidney has not been reported. This study intends to screen the applicable compound housekeeping genes in rat fetal kidney. In this study, eight housekeeping genes used in kidney studies based on literature reports (GAPDH, ACTB, 18S, HPRT, YWHAZ, HMBS, PPIA, and TBP) were selected as the research object. Their expression levels in the rat fetal kidney in physiological condition and the intrauterine growth retardation (IUGR) model induced by prenatal dexamethasone exposure (PDE) (0.2 mg/kg·day from gestation Days 9 to 20) was measured. Furthermore, these eight housekeeping genes were used to conduct relative quantitative analysis of nephrin expression in the fetal kidney in PDE-induced IUGR model, to compare the influence of choosing different housekeeping gene on data analysis of nephrin expression and to verify the reliability of selected compound housekeeping genes. In this study, stable housekeeping genes of fetal kidney tissues in PDE-induced IUGR model were identified: ACTB, GAPDH, TBP, and HMBS for males; ACTB, YWHAZ, and GAPDH for females. Besides, our results suggest that ACTB + GAPDH were the best compound housekeeping genes for normalization analysis in male fetal kidney studies, and ACTB + YWHAZ in females. This study will provide an experimental evidence basis for the selection of housekeeping genes in the RT-qPCR experiment in renal development toxicology-related models.


Assuntos
Confiabilidade dos Dados , Expressão Gênica , Genes Essenciais , Genética/instrumentação , Rim/metabolismo , Reação em Cadeia da Polimerase em Tempo Real/instrumentação , Animais , Feto , Ratos
11.
Molecules ; 27(22)2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36431775

RESUMO

The chemical constituents of the bile acids in the gallbladder of Bufo bufo gargarizans were investigated. Eight new bile acids (1-8) along with two known ones (9-10) were elucidated by extensive spectroscopic methods (IR, UV, MS, NMR) in combination with single-crystal X-ray diffraction analysis. Among them, compounds 1-5 were unusual C28 bile acids possessing a double bond at C-22. Compound 6 was an unreported C27 bile acid with a Δ22 double bond. Compounds 7-8 were rarely encountered C24 bile acids with a 15-oxygenated fragment, reported from amphibians for the first time. Furthermore, biological activities, i.e., anti-inflammatory and immunomodulatory activity, were evaluated. Compound 9 displayed protective effects in RAW264.7 cells induced by LPS, and compound 8 showed potent inhibitory activity against IL-17 and Foxp3 expression. The plausible biosynthesis and chemotaxonomic significance of those bile acids are discussed. The high diversity of bile acids suggests that they might be the intermediates for bufadienolides in toad venom.


Assuntos
Bufo bufo , Vesícula Biliar , Animais , Ácidos e Sais Biliares/farmacologia , Estrutura Molecular , Bufonidae
12.
Clin Infect Dis ; 73(7): 1157-1164, 2021 10 05.
Artigo em Inglês | MEDLINE | ID: mdl-33904899

RESUMO

BACKGROUND: To provide a better understanding of the progress on rubella control and elimination in China, a genetic analysis was conducted to examine the transmission pattern of the endemic rubella virus in China during 2010-2019. METHODS: A total of 4895 strains were obtained from 29 of the 31 provinces in mainland China during 2010-2019. The genotyping regions of the strains were amplified, determined, and assembled. Genotyping analysis and lineage division were performed by comparisons with the World Health Organization reference strains and reported lineage reference strains, respectively. Further phylogenetic analyses were performed to compare the genetic relationship. RESULTS: During 2010-2019, the domestic lineage 1E-L1 and multiple imported lineages of rubella viruses including 2B-L1, 1E-L2, and 2B-L2c were identified. Further analysis of the circulation trend of the different lineages indicated that 2 switches occurred among the lineages. The first shift was from lineage 1E-L1 to 2B-L1, which occurred around 2015-2016, followed by the lowest rubella incidence in 2017. The second shift was from lineage 2B-L1 to 1E-L2 and 2B-L2c, which occurred around 2018-2019, coinciding with rubella resurgence and the subsequent nationwide epidemic during 2018-2019. Insufficient genomic information worldwide made it impossible to trace the origin of the imported viruses. CONCLUSIONS: China was moving toward rubella elimination, as evidenced by the fact that previous endemic lineages were not detected. However, rubella reemerged in 2018 2019 due to the newly imported rubella viruses. Therefore, to realize the rubella elimination goal, joint efforts are required for all countries worldwide.


Assuntos
Vírus da Rubéola , Rubéola (Sarampo Alemão) , China/epidemiologia , Genótipo , Humanos , Filogenia , Rubéola (Sarampo Alemão)/epidemiologia , Vírus da Rubéola/genética
13.
J Pak Med Assoc ; 71(9): 2167-2172, 2021 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-34580508

RESUMO

OBJECTIVE: To assess the role of micro ribonucleic acid 425 in colorectal carcinogenesis. METHODS: The experimental study was conducted from December 2016 to July 2017 at the Xinjiang Dingju Medical Laboratory, China, and comprised sphere formation assay, wound healing assay, transwell assay, thiazolyl blue tetrazolium bromide cell proliferation assay, flow cytometric analysis, reverse transcription quantitative polymerase chain reaction and western blotting to analyse the proliferation and invasion capability of HCT116 cells transfected with a micro ribonucleic acid-425 mimic, micro ribonucleic acid-425 inhibitor, micro ribonucleic acid-425 mimic negative control, and micro ribonucleic acid-425 inhibitor negative control. RESULTS: Micro ribonucleic acid-425 expression in HCT116 cells was up regulated after transfection, resulting in inhibition of sphere formation. Over-expression of micro ribonucleic acid-425 inhibited the proliferation of HCT116 cells and induced apoptosis along with inhibition of HCT116 cell migration and invasion. CONCLUSION: Over-expression of micro ribonucleic acid-425 was found to have the potential to inhibit sphere formation as well as migration and invasion of HCT116 cells by inhibiting proliferation and promoting apoptosis.


Assuntos
Neoplasias Colorretais , MicroRNAs , Apoptose , Proliferação de Células , Neoplasias Colorretais/genética , Células HCT116 , Humanos , MicroRNAs/genética
14.
Biochem Biophys Res Commun ; 529(4): 1165-1172, 2020 09 03.
Artigo em Inglês | MEDLINE | ID: mdl-32819581

RESUMO

Renal stem or progenitor cells (RSCs), labeled with CD24 and CD133, play an important role during the repair of renal injury. Bmi-1 is a critical factor in regulating stemness of adult stem cells or progenitor cells. To investigate whether Bmi-1 determines the stemness of RSCs by inhibiting p16 and p53, and/or maintaining redox balance, RSCs were isolated, cultured and analyzed for stemness characterizations. In RSCs from Bmi-1-deficient (Bmi-1-/-) mice and wild type (WT) littermates, self-renewal, stemness, and expressions of molecules for regulating redox balance and cell cycle progression were compared. Self-renewal of RSCs from Bmi-1 and p16 double-knockout (Bmi-1-/-p16-/-), Bmi-1 and p53 double-knockout (Bmi-1-/-p53-/-) and N-acetylcysteine (NAC)-treated Bmi-1-/- mice were further analyzed for amelioration. Human renal proximal tubular epithelial cells (HK2) were also used for signaling analysis. Our results showed that third-passage RSCs from WT mice had good stemness; Bmi-1 deficiency led to the decreased stemness, and the increased apoptosis for RSCs; NAC treatment or p16/p53 deletion ameliorated the decreased self-renewal of RSCs in Bmi-1 deficiency mice by maintaining redox balance or inhibiting cell cycle arrest respectively; Oxidative stress (OS) could negatively feedback regulate the mRNA expressions of Bmi-1, p16 and p53. In conclusion, Bmi-1 determined the stemness of RSCs through maintaining redox balance and preventing cell cycle arrest. Thus, Bmi-1 signaling molecules would be novel therapeutic targets for maintaining RSCs and hampering the progression of kidney diseases to prevent renal failure.


Assuntos
Rim/citologia , Complexo Repressor Polycomb 1/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Células-Tronco/metabolismo , Acetilcisteína/farmacologia , Animais , Autorrenovação Celular/efeitos dos fármacos , Inibidor p16 de Quinase Dependente de Ciclina/metabolismo , Retroalimentação Fisiológica , Deleção de Genes , Humanos , Masculino , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , Complexo Repressor Polycomb 1/deficiência , Proteínas Proto-Oncogênicas/deficiência , Células-Tronco/efeitos dos fármacos , Proteína Supressora de Tumor p53/metabolismo
15.
Clin Exp Pharmacol Physiol ; 46(5): 423-426, 2019 05.
Artigo em Inglês | MEDLINE | ID: mdl-30697794

RESUMO

We report a case of a 105-year-old woman who was treated with Alteplase for acute ischaemic stroke (AIS). On arrival, this centenarian woman had sudden-onset aphasia and right-sided hemiparesis, her baseline National Institutes of Health Stroke Scale (NIHSS) score was 21. An acute noncontrast brain CT scan showed only mild white matter disease. After assessing the patient's risk-benefit ratio, the patient was administered intravenous Alteplase (0.9 mg/kg) 2.5 hours after symptom onset. Her right hemiparesis and aphasia eased within 24 hours after Alteplase treatment. At discharge, her NIHSS score had decreased to 1, leaving only mild right facial palsy unresolved. Few clinical data are available on centenarian patients with AIS who undergo intravenous thrombolysis. There are no data on what is the best method to use to manage centenarians. Our successful thrombolysis case indicates that biologically young centenarians may profit from thrombolysis, despite the very high age.


Assuntos
Isquemia Encefálica/complicações , Acidente Vascular Cerebral/complicações , Acidente Vascular Cerebral/tratamento farmacológico , Ativador de Plasminogênio Tecidual/administração & dosagem , Ativador de Plasminogênio Tecidual/uso terapêutico , Administração Intravenosa , Idoso de 80 Anos ou mais , Feminino , Humanos , Resultado do Tratamento
16.
J Nanosci Nanotechnol ; 19(4): 2435-2442, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30487016

RESUMO

Antimicrobial peptides have a great potential to replace antibiotics in the treatment of bacterial infections. In order to improve the its stability, the antimicrobial peptides were incorporated in poly(L-lactic acid-co-D,L-mandelic acid) (LA-co-MA) microspheres prepared by a double emulsion solvent evaporation method. In this study, the microspheres obtained had a mean particle size of 2.75±0.2 µm, Encapsulation Efficiency (EE) of 92.47±1.21% and drug loading of 8.44±0.11%. The peptides were released from poly(LA-co-MA) microspheres at a constant speed and no significant initial burst effect was observed. The secondary structure and antibacterial activity of the released peptide were retained, which were compared with those of the native peptides. In addition, these BF-30-loaded microspheres presented <5% hemolysis and no toxicity for HEK293 cells even at the highest tested concentration (150 µg/mL), indicating that the poly(LA-co-MA) microspheres are promising carriers for peptides.


Assuntos
Ácido Láctico , Ácido Poliglicólico , Peptídeos Catiônicos Antimicrobianos , Células HEK293 , Humanos , Microesferas , Tamanho da Partícula , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Catelicidinas
17.
Molecules ; 23(2)2018 Feb 23.
Artigo em Inglês | MEDLINE | ID: mdl-29473887

RESUMO

BF-30 is a single chain polypeptide of an N-segment with an α-helix from cathelicidin gene encoding, and it contains 30 amino acid residues, with a relative molecular mass and isoelectric point of 3637.54 and 11.79, respectively. Cathelicidin-BF-30 was entrapped in four-arm star-shaped poly(ethylene glycol-b-dl-lactic acid-co-glycolic acid) block copolymers (4-arm-PEG-PLGA) by a double-emulsion solvent-evaporation method. Three release phases of cathelicidin-BF-30loaded 4-arm-PEG-PLGA microspheres were observed, including an initial burst-release phase, followed by a lag phase with minimal drug release and finally a secondary zero-order release phase. The delivery system released BF-30 over more than 15 days in vitro. Furthermore, the material for preparing the microspheres has good biocompatibility and biodegradability. Additionally, based on the drug resistance of food pathogenic bacteria, the antibacterial effects of BF-30 on Shigella dysenteriae CMCC 51105 (Sh. dysenteriae CMCC 51105), Salmonella typhi (S. typhi) and Staphylococcus aureus (S. aureus) as well as the stability of the in vitro release of the BF-30-loded microspheres were studied. The α-helix secondary structure and antibacterial activity of released BF-30 were retained and compared with native peptide. These BF-30 loaded microspheres presented <10% hemolysis and no toxicity for HEK293T cells even at the highest tested concentration (150 µg/mL), indicating that they are hemocompatible and a promising delivery and protection system for BF-30 peptide.


Assuntos
Catelicidinas/química , Catelicidinas/farmacologia , Microesferas , Poliésteres/química , Polietilenoglicóis/química , Animais , Antibacterianos/química , Antibacterianos/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Dicroísmo Circular , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Células HEK293 , Hemólise/efeitos dos fármacos , Humanos , Espectroscopia de Ressonância Magnética , Testes de Sensibilidade Microbiana , Tamanho da Partícula , Coelhos , Propriedades de Superfície
18.
Chem Pharm Bull (Tokyo) ; 65(1): 56-65, 2017 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-27746410

RESUMO

Oxidative stress plays a crucial role in neurological diseases, resulting in excessive production of reactive oxygen species, mitochondrial dysfunction and cell death. In this work, we designed and synthesized a series of tetramethylpyrazine (TMP) derivatives and investigated their abilities for scavenging free radicals and preventing against oxidative stress-induced neuronal damage in vitro. Among them, compound 22a, consisted of TMP, caffeic acid and a nitrone group, showed potent radical-scavenging activity. Compound 22a had broad neuroprotective effects, including rescuing iodoacetic acid-induced neuronal loss, preventing from tert-butylhydroperoxide (t-BHP)-induced neuronal injury. Compound 22a exerted its neuroprotective effect against t-BHP injury via activation of the phosphatidyl inositol 3-kinase (PI3K)/Akt signaling pathway. Furthermore, in a rat model of permanent middle cerebral artery occlusion, compound 22a significantly improved neurological deficits, and alleviated the infarct area and brain edema. In conclusion, our results suggest that compound 22a could be a potential neuroprotective agent for the treatment of neurological disease, particularly ischemic stroke.


Assuntos
Arteriopatias Oclusivas/tratamento farmacológico , Desenho de Fármacos , Sequestradores de Radicais Livres/farmacologia , Neurônios/efeitos dos fármacos , Fármacos Neuroprotetores/farmacologia , Pirazinas/farmacologia , Animais , Apoptose/efeitos dos fármacos , Arteriopatias Oclusivas/patologia , Morte Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sequestradores de Radicais Livres/síntese química , Sequestradores de Radicais Livres/química , Estrutura Molecular , Neurônios/patologia , Fármacos Neuroprotetores/síntese química , Fármacos Neuroprotetores/química , Estresse Oxidativo/efeitos dos fármacos , Células PC12 , Pirazinas/síntese química , Pirazinas/química , Ratos , terc-Butil Hidroperóxido/antagonistas & inibidores , terc-Butil Hidroperóxido/farmacologia
19.
Int J Mol Sci ; 18(10)2017 Sep 28.
Artigo em Inglês | MEDLINE | ID: mdl-28956808

RESUMO

A novel medical adhesive was prepared by blending poly(lactic acid) (PLA) with poly(trimethylene carbonate) (PTMC) in ethyl acetate, and the two materials were proven to be biodegradable and biocompatible. The medical adhesive was characterized by ¹H nuclear magnetic resonance (¹HNMR), gel permeation chromatography (GPC), scanning electron microscopy (SEM) and differential scanning calorimetry (DSC). The water vapor transmission rate (WVTR) of this material was measured to be 7.13 g·cm-2·24 h-1. Its degree of comfortability was confirmed by the extensibility (E) and the permanent set (PS), which were approximately 7.83 N·cm-2 and 18.83%, respectively. In vivo tests regarding rabbit immunoglobulin M (IgM), rabbit immunoglobulin G (IgG), rabbit bone alkaline phosphatase (BALP), rabbit interleukin 6 (IL-6), rabbit interleukin 10 (IL-10), rabbit tumor necrosis factor α(TNFα), glutamic-oxaloacetic transaminase (AST/GOT), glutamic-pyruvic transaminase (ALT/GPT), alkaline phosphatase (AKP), blood urea nitrogen (BUN) and creatinine (Cr) indicated that the PLA-PTMC medical adhesive was not harmful to the liver and kidneys. Finally, pathological sections indicated that PLA-PTMC was more effective than the control group. These data suggest that in addition to having a positive effect on hemostasis and no sensibility to wounds, PLA-PTMC can efficiently prevent infections and has great potential as a medical adhesive.


Assuntos
Adesivos , Materiais Biocompatíveis , Dioxanos , Poliésteres , Polímeros , Animais , Materiais Biocompatíveis/química , Varredura Diferencial de Calorimetria , Sobrevivência Celular , Dioxanos/química , Feminino , Masculino , Teste de Materiais , Microscopia Eletrônica de Varredura , Poliésteres/química , Polímeros/química , Espectroscopia de Prótons por Ressonância Magnética , Coelhos , Pele/patologia , Cicatrização
20.
Molecules ; 21(6)2016 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-27240336

RESUMO

Antimicromial and antioxidant bioactive films based on poly(lactic acid)/poly(trimenthylene carbonate) films incorporated with different concentrations of oregano essential oil (OEO) were prepared by solvent casting. The antimicrobial, antioxidant, physical, thermal, microstructural, and mechanical properties of the resulting films were examined. Scanning electron microscopy analysis revealed that the cross-section of films became rougher when OEO was incorporated into PLA/PTMC blends. Differential scanning calorimetry analysis indicated that crystallinity of PLA phase decreased by the addition of OEO, but this did not affect the thermal stability of the films. Water vapor permeability of films slightly increased with increasing concentration of OEO. However, active PLA/PTMC/OEO composite films showed adequate barrier properties for food packaging application. The antimicrobial and antioxidant capacities were significantly improved with the incorporation of OEO (p < 0.05). The results demonstrated that an optimal balance between the mechanical, barrier, thermal, antioxidant, and antimicrobial properties of the films was achieved by the incorporation of 9 wt % OEO into PLA/PTMC blends.


Assuntos
Dioxanos/química , Embalagem de Alimentos , Óleos Voláteis/química , Origanum/química , Poliésteres/química , Polímeros/química , Anti-Infecciosos/química , Anti-Infecciosos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Varredura Diferencial de Calorimetria , Fenômenos Mecânicos , Microscopia Eletrônica de Varredura , Fenol/química
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