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The Ni-catalyzed enantioselective addition reaction of aryl halides to aldehydes was studied with cyanobis(oxazoline) as chiral ligands and Mn as reductant. Aryl and heteroaryl bromides reacted with phenyl aldehyde at room temperature to produce dibenzyl alcohols in 16-99 % yields with 53-92 % ees. Moreover, the coupling of phenyl chloride with a variety of aryl, heteroaryl and alkyl aldehydes was demonstrated in the presence of cyanobis(oxazoline)/Ni(II) at 60 °C in generally high yields with moderate enantioselectivities.
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Three new flavan derivatives including two methylene-linked flavan-3-ol dimers, bis(8-epiafzelechinyl)methane (1), and 8,8-(epiafzelechin-afzelechin)methane (2), a flavan-3-ol monomer, (-)-3-O-acetyl-epiafzelechin (3) and four known related compounds (4-7) were isolated from the leaves and stems of Cassia nodosa. Their structures were elucidated by extensive spectroscopic analyses and CD data. The isolates were evaluated for their antioxidant, α-glucosidase inhibitory, cytotoxic and neuroinflammatory activities, and compound 3 exhibited remarkable radical scavenging activities in both the DPPH and ABTS models with IC50 values of 2.65±1.25, and 4.78±0.91 µg/mL, respectively.
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AIMS: This work aimed to analyse retrospective data on hypotension incidence and associated factors among patients requiring continuous renal replacement therapy. BACKGROUND: The incidence and risk factors of continuous renal replacement therapy-related hypotension have not been adequately explored. DESIGN: The study was designed as a retrospective analysis. METHODS: Patients who required continuous renal replacement therapy in the ICU between January 2017 and June 2021 were reviewed. The multivariate logistic regression model was used to determine the associated factors of hypotension. RESULTS: Hypotension occurred in 242 out of 885 circuits (27.3%) among 140 patients. The logistic regression analysis identified seven factors associated with the occurrence of hypotension during CRRT: serum albumin (OR = 0.969, 95%CI: 0.934-0.999), serum calcium (OR = 0.514, 95%CI: 0.345-0.905), CO2CP (OR = 0.933, 95%CI: 0.897-0.971), use of vasopressors (OR = 5.731, 95%CI: 4.023-8.165), hypotension before CRRT initiation (OR = 2.779, 95%CI:1.238-6.242), age (OR = 1.016, 95%CI: 1.005-1.027), and fluid removal rate (OR = 1.002, 95%CI: 1.001-1.003). CONCLUSIONS: Hypotension frequently occurs in patients receiving continuous renal replacement therapy, especially in the early stages. Multiple factors can be associated with cardiac output or peripheral resistance changes, including excessive ultrafiltration, vasopressors, serum albumin and serum calcium levels, and carbon dioxide combining power.
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BACKGROUND: Short tandem repeats (STR) are highly polymorphic DNA markers utilised in forensic personal identification and human population genetic research. Guizhou Tujia is one of the ancient minority groups in southwest China, however, the population has not been studied using the highly discriminating 23 STR Huaxia Platinum Kit. AIM: To obtain genetic data from 23 autosomal STRs in Guizhou Tujia and examine the population's relationship with others. SUBJECTS AND METHODS: A total of 480 individuals from the Guizhou Tujia population were analysed using 23 STR loci of Huaxia Platinum Kit. Allele frequencies and forensic parameters were estimated. Population genetic relationships were calculated by Nei's genetic distances and visualised using a variety of biostatistical methods. RESULTS: A total of 264 alleles were found, with allelic frequencies ranging from 0.0010 to 0.5104. The combined discrimination power (CDP) and the combined probability of paternity (CPE) of 23 STR loci were 0.9999999999999999999999999996 and 0.999999999710422, respectively. Guizhou Tujia showed closer genetic relationships with Hubei Tujia, Guizhou Gelao, and Guizhou Miao than with other populations. CONCLUSION: We first obtained the population genetic data of Guizhou Tujia using the 23 STR system and demonstrated its value in forensic applications. Comprehensive population comparisons showed an evident genetic affinity pattern between populations that are geographically, ethnically and linguistically related.
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Minorias Étnicas e Raciais , Grupos Minoritários , Humanos , Filogenia , Etnicidade/genética , Platina , Repetições de Microssatélites/genética , Variação GenéticaRESUMO
A Gram-stain-positive, non-flagellated, non-gliding, coccoid bacterial strain, designated JLT9T, was isolated from the shallow-sea hydrothermal system off Kueishantao Island, Taiwan, ROC. Strain JLT9T was aerobic, chemoheterotrophic and grew optimally at 35 °C, at pH 6.0 and in the presence of 2.5â% (w/v) NaCl. Strain JLT9T exhibited highest 16S rRNA gene sequence similarity to Serinicoccus marinus DSM 15273T (98.83â%). Phylogenetic trees based on 16S rRNA gene sequences revealed that strain JLT9T belonged to the genus Serinicoccus, clustering with Serinicoccus marinus JC1078T, Serinicoccus profundi MCCC 1A05965T, Serinicoccus sediminis GP-T3-3T and Serinicoccus chungangensis CAU9536T. The digital DNA-DNA genome hybridization values between strain JLT9T and the closest related strain S. marinus DSM 15273T was 34.30â%. The DNA G+C content was 72.43âmol%. The dominant fatty acids were identified as iso-C15â:â0 (41.4â%) and iso-C16â:â0 (24.7â%). The polar lipids of strain JLT9T comprised diphosphatidylglycerol, phosphatidylcholine, phosphatidylglycerol, three unidentified glycolipid and an unidentified phospholipid. The predominant isoprenoid quinone was MK-8 (H4). The cell wall contained ornithine and serine, and no diaminopimelic acid. On the basis of phylogenetic data and several distinct phenotypic characteristics, strain JLT9T represents a novel species of the genus Serinicoccus, for which the name Serinicoccus hydrothermalis sp. nov. is proposed. The type strain is JLT9T (=CGMCC 1.15779T=JCM 31502T).
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Actinomycetales/classificação , Fontes Hidrotermais/microbiologia , Filogenia , Água do Mar/microbiologia , Actinomycetales/isolamento & purificação , Técnicas de Tipagem Bacteriana , Composição de Bases , Parede Celular/química , DNA Bacteriano/genética , Ácido Diaminopimélico/química , Ácidos Graxos/química , Glicolipídeos/química , Ilhas , Hibridização de Ácido Nucleico , Peptidoglicano/química , Fosfolipídeos/química , RNA Ribossômico 16S/genética , Análise de Sequência de DNA , Taiwan , Vitamina K 2/análogos & derivados , Vitamina K 2/químicaRESUMO
Cervical carcinoma is known as one of the most lethal and common conditions in women worldwide. Increasing evidence shows that microRNAs (miRs) may be involved in the pathogenesis of cervical carcinoma. This study investigates the correlation between expression of miR-224 in peripheral blood mononuclear cells and both diagnosis and prognosis of cervical carcinoma to clarify the effect miR-224 has on the biological behaviors of the subjected cervical carcinoma cells. Initially, 132 patients diagnosed with cervical carcinoma and 120 healthy subjects were recruited. Peripheral blood expression of miR-224 and PTX3 was detected. A telephone follow-up was performed every 3 months after treatment. The diagnostic value of miR-224 in cervical carcinoma was analyzed using the Receiver Operating Characteristic curve. The effects of both miR-224 and PTX3 on cell proliferation, migration, and invasion were evaluated with an intervention of miR-224 ectopic expression or depletion and PTX3 silencing. The bioinformatics prediction website and dual-luciferase reporter assay revealed PTX3 to be a target gene for miR-224. Moreover, miR-224 was detected as over-expressed, but PTX3 was under-expressed in cervical carcinoma. Additionally, as a diagnostic biomarker, a high miR-224 expression was closely linked with the progression of cervical carcinoma. Both miR-224 overexpression and PTX3 silencing promoted cell proliferation, migration, and invasion, whereas, the aforementioned properties were depressed when miR-224 was inhibited. Altogether, the miR-224 overexpression may be a biological indicator in predicting the progression of cervical carcinoma. Thus, miR-224 inhibition may significantly prevent cervical carcinoma progression by targeting the PTX3 gene.
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Proteína C-Reativa/genética , Carcinoma/genética , MicroRNAs/genética , Componente Amiloide P Sérico/genética , Neoplasias do Colo do Útero/genética , Adulto , Idoso , Apoptose/genética , Carcinoma/patologia , Movimento Celular/genética , Proliferação de Células/genética , Feminino , Regulação Neoplásica da Expressão Gênica/genética , Células HeLa , Humanos , Pessoa de Meia-Idade , Prognóstico , Neoplasias do Colo do Útero/patologiaRESUMO
BACKGROUND Acute cerebral infarction is a major clinical subtype of ischemic stroke that has become a leading cause of death and disability worldwide. Aldehyde dehydrogenase 2 (ALDH2) is an important oxidative enzyme in alcohol metabolism. The polymorphism of ALDH2 Glu504Lys polymorphism modifies the activity of this enzyme. However, the potential association between the allelic variation of ALDH2 Glu504Lys with collateral circulation and short-term prognosis of acute cerebral infarction remains unclear. MATERIAL AND METHODS A total of 394 patients with acute cerebral infarction were recruited for ALDH2 genotyping using direct sequencing. Cerebrovascular stenosis and collateral circulation were evaluated by digital subtraction angiography (DSA). Short-term prognosis was assessed in accordance with the modified Ranking Scale (mRS). RESULTS We identified 297 as EAS and 394 as IAS. There were more patients with occluded blood vessel in the opened group and far fewer in the unopened group. ALDH2 polymorphism was significantly different among the primary, secondary, and tertiary opened groups. ALDH2 gene Glu504Lys was significantly associated with short-term prognosis. The genotype GA+AA of ALDH2 gene Glu504Lys locus was an independent risk factor of poor 90-day prognosis. CONCLUSIONS ALDH2 Glu504Lys could be a risk factor for collateral circulation and a negative predictor for short-term prognosis in acute cerebral infarction in Han Chinese. ALDH2 Glu504Lys could be a new therapeutic target for patients with acute cerebral infarction.
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Aldeído-Desidrogenase Mitocondrial/genética , Infarto Cerebral/genética , Adulto , Idoso , Aldeído-Desidrogenase Mitocondrial/metabolismo , Alelos , Angiografia Digital/métodos , Povo Asiático/genética , Isquemia Encefálica/genética , Infarto Cerebral/fisiopatologia , Circulação Colateral/genética , Feminino , Frequência do Gene/genética , Predisposição Genética para Doença , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética , Prognóstico , Fatores de Risco , Acidente Vascular Cerebral/genéticaRESUMO
Transplantation of mesenchymal stem cells may inhibit pathological immune processes contributing to ischemia/reperfusion (I/R) injury. This study aimed to assess the capacity of human amniotic MSC (hAMSCs) to ameliorate I/R injury in a dog model of cardiopulmonary bypass (CPB). Dissociated hAMSCs were cultured ex vivo, and their immunophenotypes were assessed by flow cytometry and immunohistochemistry. A dog model of CPB was established by surgical blockage of the aorta for 1 h. Dogs either underwent mock surgery (Sham group), CPB (model group), or CPB, followed by femoral injection of 2 × 10(7) hAMSCs (n=6). Anti-human nuclei staining revealed hAMSCs in the lungs 3 h after surgery. Oxygen index (OI) and respiratory index (RI) of arterial blood were measured using a biochemical analyzer. Venous blood TNF-α, IL-8, MMP-9, and IL-10 concentrations were measured by ELISA. Pathological changes in the lung were assessed by light microscopy. Third-generation-cultured hAMSCs expressed high levels of CD29, CD44, CD49D, CD73, and CD166 levels, but low CD34 or CD45 amounts and their cytoplasm contained Vimentin. In CPB model animals, OI was elevated and RI reduced; TNF-α, IL-8, and MMP-9 levels were elevated, and IL-10 levels reduced within 3h (P<0.05), but hAMSC transplantation significantly ameliorated these changes (P<0.05). Pathological changes observed in the hAMSC group were significantly less severe than those in the CPB group. In conclusion, hAMSC transplantation can downregulate proinflammatory factors and reduce MMP-9 levels, whereas upregulating the anti-inflammatory molecule IL-10, thus reducing I/R lung injury in a dog model of CPB.
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Lesão Pulmonar/terapia , Transplante de Células-Tronco Mesenquimais , Traumatismo por Reperfusão/terapia , Âmnio/citologia , Animais , Ponte Cardiopulmonar/efeitos adversos , Células Cultivadas , Modelos Animais de Doenças , Cães , Feminino , Xenoenxertos , Humanos , Mediadores da Inflamação/metabolismo , Lesão Pulmonar/patologia , Lesão Pulmonar/fisiopatologia , Células-Tronco Mesenquimais/citologia , Células-Tronco Mesenquimais/metabolismo , Traumatismo por Reperfusão/patologia , Traumatismo por Reperfusão/fisiopatologia , Vimentina/metabolismoRESUMO
AIM: Aldehyde dehydrogenase 2 (ALDH2) is a key enzyme that metabolizes acetaldehyde to acetic acid. ALDH2 gene polymorphism modifies its activity and the mutation of ALDH2 gene has been reported to be associated with the protection against ischemic stroke. However, the potential association of allelic variation of ALDH2 with intracranial vascular stenosis and the clinical characteristics of ischemic stroke without coronary artery disease remains unclear. METHODS: In this study, ischemic stroke patients were recruited, National Institutes of Health Stroke Scale scores were analyzed, intracranial arterial stenosis were evaluated by magnetic resonance angiography and gene typing of ALDH2 was determined by polymerase chain reaction and sequencing. RESULTS: We found that the rate of heavy drinking was significantly lower in the ALDH2 mutation group ((*)1/(*)2 and (*)2/(*)2) than in wild-type group ((*)1/(*)1) (18.6% vs. 38.0%, p = 0.01). Plasma homocysteine (Hcy) levels were significantly different in the two groups (15.45 ± 6.39 vs. 13.14 ± 4.45, p = 0.015). The ALDH2 mutation genotype was negatively correlated with severe intracranial vascular stenosis (OR, 0.34; p = 0.002), even after adjustment for high-density lipoprotein cholesterol, Hcy, and heavy drinking (adjusted OR, 0.44; p = 0.03). CONCLUSION: ALDH2(*)2 could be a protective factor and negative predictor for severe intracranial vascular stenosis in ischemic stroke in Han Chinese.
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Aldeído Desidrogenase/genética , Povo Asiático/genética , Constrição Patológica/genética , Doenças Arteriais Intracranianas/genética , Acidente Vascular Cerebral/genética , Consumo de Bebidas Alcoólicas/genética , Alelos , Estudos de Casos e Controles , Feminino , Predisposição Genética para Doença/genética , Homocisteína/sangue , Humanos , Angiografia por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Mutação , Polimorfismo Genético/genética , Fatores de Proteção , Fatores de Risco , Acidente Vascular Cerebral/sangueRESUMO
Since the release rate of protein in hydrogels is directly dependent upon the size of the protein and the hydrogel, how to deliver low molecular weight protein for prolonged periods has always been a problem. In this article, we present a usage of self-assembling peptide (P3) with the RGD epitope on its N terminus. The concentration of the released insulin-like growth factor 1 (IGF-1) was determined by UV-vis spectroscopy and the release kinetics suggested a notable reduction of the IGF-1 release rate. Cell entrapment experiments revealed that IGF-1 delivery by biotinylated nanofibers could promote the proliferation of the mouse chondrogenic ATDC5 cells when compared with cells embedded within nanofibers with untethered IGF-1.
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Portadores de Fármacos/química , Hidrogéis/química , Fator de Crescimento Insulin-Like I/farmacologia , Animais , Biotina , Linhagem Celular , Preparações de Ação Retardada , Camundongos , Nanofibras , Oligopeptídeos/químicaRESUMO
Application research on human amniotic membrane has been carried out for nearly a hundred years and people found that there were more than dozens of kinds bioactive substances in the amniotic membrane. It has been proved that the amniotic membrane has a lot of functions, such as anti-inflammatory, anti-bacterial, anti-virus, anti-angiogenic and promoting cell apoptosis, and soon. As effective treatments, amniotic membrane has been used for adjunctive therapy of burns, trauma, ophthalmic damage, dermatopathya. Recent advances of amniotic membrane and amniotic membrane-derived cells research have led to enormous progress in skin tissue engineering, vascular tis- sue engineering, biological scaffold material, and biological sustained-release materials. Amniotic membrane and amniotic membrane derived cells have a significant advantage and unique charm in medical field. Therefore, they have higher research value and broad prospects in the applications.
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Âmnio , Engenharia Tecidual , Pesquisa Biomédica/tendências , Humanos , Resultado do TratamentoRESUMO
BACKGROUND: Chondrocyte ferroptosis plays a critical role in the pathogenesis of osteoarthritis (OA), regulated by the SLC7A11/GPX4 signaling pathway. Icariin (ICA), a flavonoid glycoside, exhibits strong anti-inflammatory and antioxidant activities. This study investigated whether ICA could modulate the SLC7A11/GPX4 signaling to inhibit chondrocyte ferroptosis and alleviate OA. PURPOSE: The objective was to explore the impact of ICA on chondrocyte ferroptosis in OA and its modulation of the SLC7A11/GPX4 signaling pathway. METHODS: The anti-ferroptosis effects of ICA were evaluated in an interleukin-1ß (IL-1ß)-treated SW1353 cell model, using Ferrostatin-1 (Fer-1) and Erastin (Era) as ferroptosis inhibitor and inducer, respectively, along with GPX4 knockdown via lentivirus-based shRNA. Additionally, the therapeutic efficacy of ICA on OA-related articular cartilage damage was assessed in rats through histopathology and immunohistochemistry (IHC). RESULTS: IL-1ß treatment upregulated the expression of OA-associated matrix metalloproteinases (MMP3 and MMP1), a disintegrin and metalloproteinase with thrombospondin motifs (ADAMTS-5), and increased intracellular ROS, lipid ROS, and MDA levels while downregulating collagen II and SOX9 expression in SW1353 cells. ICA treatment countered the IL-1ß-induced upregulation of MMPs and ADAMTS-5, restored collagen II and SOX9 expression, and reduced intracellular ROS, lipid ROS, and MDA levels. Furthermore, IL-1ß upregulated P53 but downregulated SLC7A11 and GPX4 expression in SW1353 cells, effects that were mitigated by ICA or Fer-1 treatment. Significantly, ICA also alleviated Era-induced ferroptosis, whereas it had no effect on GPX4-silenced SW1353 cells. In vivo, ICA treatment reduced articular cartilage damage in OA rats by partially restoring collagen II and GPX4 expression, inhibiting cartilage extracellular matrix (ECM) degradation and chondrocyte ferroptosis. CONCLUSION: ICA treatment mitigated chondrocyte ferroptosis and articular cartilage damage by enhancing the SLC7A11/GPX4 signaling, suggesting its potential as a therapeutic agent for OA interventions.
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Sistema y+ de Transporte de Aminoácidos , Condrócitos , Ferroptose , Flavonoides , Osteoartrite , Fosfolipídeo Hidroperóxido Glutationa Peroxidase , Transdução de Sinais , Animais , Humanos , Masculino , Ratos , Sistema y+ de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/genética , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Cartilagem Articular/efeitos dos fármacos , Cartilagem Articular/patologia , Cartilagem Articular/metabolismo , Linhagem Celular , Condrócitos/efeitos dos fármacos , Condrócitos/metabolismo , Ferroptose/efeitos dos fármacos , Flavonoides/farmacologia , Flavonoides/uso terapêutico , Interleucina-1beta/metabolismo , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo , Osteoartrite/patologia , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/metabolismo , Fosfolipídeo Hidroperóxido Glutationa Peroxidase/genética , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacosRESUMO
We report herein a mild and catalytic phosphonofluorination of unactivated alkenes. With catalysis by AgNO3, the condensation of various unactivated alkenes with diethyl phosphite and Selectfluor reagent in CH2Cl2/H2O/HOAc at 40 °C led to the efficient synthesis of ß-fluorinated alkylphosphonates with good stereoselectivity and wide functional group compatibility. A mechanism involving silver-catalyzed oxidative generation of phosphonyl radicals and silver-assisted fluorine atom transfer is proposed.
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Alcenos/química , Compostos de Diazônio/química , Hidrocarbonetos Fluorados/síntese química , Compostos Organofosforados/química , Nitrato de Prata/química , Catálise , HalogenaçãoRESUMO
OBJECTIVE: To investigate the effects of Weile Powder (WLP) on bicarbonate transporters in rats with gastric ulcers, and to probe its functional mechanisms. METHODS: The 48 SD rats were randomly divided into the normal control group, the model group, the low dose WLP group (at the daily dose of 0.075 g/mL), the middle dose WLP group (at the daily dose of 0.150 g/mL), the high dose WLP group (at the daily dose of 0.030 g/mL), and the ranitidine group (at the daily dose of 0.030 g/mL), 8 in each group. The gastric ulcer rat model was prepared by the glacial acetic acid cauterization method. Rats in each medication group were administered from the 2nd day of modeling. Rats were sacrificed after 14-day successive medication. The protein was extracted from the ulcer tissue. The protein expressions of solute carrier26A3 (SLC26A3)and solute carrier26A6 (SLC26A6) were detected using Western blot. The gastric ulcer and its peripheral tissue were sectioned. The changes of cystic fibrosis transmembrane conductance regulator (CFTR) were measured by immunofluorescence. RESULTS: Compared with the model control group, the expression levels of SLC26A3 increased in the high dose WLP group and the ranitidine group with statistical difference (P < 0.05). The expression levels of SLC26A6 increased in the high and middle dose WLP groups and the ranitidine group with statistical difference (P < 0.05). The expression level of CFTR also obviously increased in the high and middle dose WLP groups (P < 0.01). CONCLUSION: WLP could elevate the expression levels of SLC26A6, SLC26A3, and CFTR, increase the secretion of bicarbonate, thus protecting the gastric mucosa.
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Antiporters/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Mucosa Gástrica/metabolismo , Úlcera Gástrica/metabolismo , Animais , Bicarbonatos/metabolismo , Regulador de Condutância Transmembrana em Fibrose Cística/metabolismo , Feminino , Mucosa Gástrica/efeitos dos fármacos , Masculino , Ratos , Ratos Sprague-Dawley , Transportadores de SulfatoRESUMO
INTRODUCTION: Postoperative atrial fibrillation (POAF) and pericardial effusion are important factors affecting prognosis after cardiac surgery. Recently, it has been reported that posterior pericardiotomy (PP) can effectively prevent the occurrence of POAF and pericardial effusion. To validate these conclusions and guide clinical practice, we conducted a systematic review with meta-analysis. METHODS: We searched multiple databases for manuscripts published before July 2022 on the use of PP to prevent POAF and pericardial effusion and included only randomized controlled trials. The main outcome was atrial fibrillation after coronary artery bypass grafting, and secondary outcomes were included. RESULTS: This meta-analysis included 14 randomized controlled trials with a total of 2275 patients. Meta-analysis showed that the incidence of POAF after cardiac surgery in the PP group was significantly lower than that in the control group (risk ratio=0.48; 95% confidence interval=0.33~0.69; P<0.00001). PP effectively reduced postoperative pericardial effusion (risk ratio=0.34, 95% confidence interval=0.21-0.55; P<0.00001). CONCLUSION: PP has shown good results in preventing POAF, pericardial effusion, and other complications, which indicates that PP is a safe and effective surgical method, but attention still needs to be paid to the potential risk of coagulation dysfunction caused by PP.
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Fibrilação Atrial , Procedimentos Cirúrgicos Cardíacos , Derrame Pericárdico , Ferida Cirúrgica , Humanos , Fibrilação Atrial/etiologia , Fibrilação Atrial/prevenção & controle , Derrame Pericárdico/etiologia , Derrame Pericárdico/prevenção & controle , Resultado do Tratamento , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Complicações Pós-Operatórias/etiologia , Complicações Pós-Operatórias/prevenção & controle , Fatores de RiscoRESUMO
Background and Aims: Diabetic kidney disease (DKD) is a prevalent and intractable microvascular complication of diabetes mellitus (DM), the process of which is closely related to abnormal expression of angiogenesis-regulating factors (ARFs). Stem cell transplantation might be a novel strategy for treating DKD. This study aims to explore the effect of transplantation of human amniotic mesenchymal stem cells (hAMSCs) on renal microangiopathy in a type 1 DKD rat model (T1DRM). Methods: Seventy-two rats were randomly divided into three groups, including normal control group, DKD group, and hAMSCs transplantation group. T1DRM was established using a rat tail vein injection of streptozotocin (STZ) (55 mg/kg). hAMSCs were obtained from placental amniotic membranes during cesarean delivery and transplanted at 3 and 4 weeks through penile veins. At 6, 8, and 12 weeks following transplantation, blood glucose levels, renal function, pathological kidney alterations, and the expressions of ARFs' mRNA and protein were analyzed. Results: In T1DRM, transplanted hAMSCs that were homed at the injured site of kidneys increased ARFs' expression and decreased blood glucose levels. Compared to the DKD group, the levels of 24-h urinary protein, serum creatinine, urea, and kidney injury molecule-1 (KIM-1) were reduced in hAMSCs transplantation group. In terms of renal pathology such as the degree of basement membrane thickening, hAMSCs transplantation was also less severe than the DKD group, thereby alleviating kidney injury. Conclusion: hAMSCs transplantation might ameliorate STZ-induced chronic kidney injury through increasing ARFs' expression in kidneys and lowering blood glucose levels.
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Calcium-sensing receptor (CaSR) is a G protein-coupled receptor, widely distributed in various tissues, including vascular endothelial cells and smooth muscle cells, which plays an important role in the migration and homing of stem/progenitor cells and the proliferation of tissue cells. Restenosis after Percutaneous coronary intervention (PCI) seriously affects its prognosis and application. Our previous research has found that ginsenoside Rg1 (GS-Rg1) can inhibit the occurrence of restenosis after balloon injury of the common carotid artery in rats, but the mechanism is still unclear. In this study, it was found that GS-Rg1 (4, 8, 16 mg/kg) inhibited vascular restenosis caused by balloon injury, and mobilize endothelial progenitor cells (EPCs) to promote reendothelialization and inhibit intimal hyperplasia, which significantly reduced after administration of CaSR antagonist NPS 2143. Interestingly, CaSR and its downstream JNK, P38 were highly expressed in the proliferative intima and participated in the abnormal proliferation of vascular smooth muscle cells mediated by smooth muscle progenitor cells (SMPCs). GS-Rg1 inhibited intimal hyperplasia, while it decreased the expression of CaSR, JNK, and P38. This might relate to the distribution of CaSR and the facilitation of GS-Rg1 on the vascular endothelial repair. It is concluded that CaSR plays a key role in GS-Rg1 promoting reendothelialization to inhibit intimal hyperplasia after balloon Injury.
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Células Progenitoras Endoteliais , Intervenção Coronária Percutânea , Ratos , Animais , Hiperplasia , Receptores de Detecção de Cálcio , Constrição PatológicaRESUMO
Objective: DNA methylation plays a potential role in the pathogenesis of Alzheimer's disease (AD). However, little is known about the global changes of blood leukocyte DNA methylome profiles from Chinese patients with mild cognitive impairment (MCI) and with AD, or the specific DNA methylation-based signatures associated with MCI and AD. In this study, we sought to dissect the characteristics of blood DNA methylome profiles in MCI- and AD-affected Chinese patients with the aim of identifying novel DNA methylation biomarkers for AD. Methods: In this study, we profiled the DNA methylome of peripheral blood leukocytes from 20 MCI- and 20 AD-affected Chinese patients and 20 cognitively healthy controls (CHCs) with the Infinium Methylation EPIC BeadChip array. Results: We identified significant alterations of the methylome profiles in MCI and AD blood leukocytes. A total of 2,582 and 20,829 CpG sites were significantly and differentially methylated in AD and MCI compared with CHCs (adjusted p < 0.05), respectively. Furthermore, 441 differentially methylated positions (DMPs), aligning to 213 unique genes, were overlapped by the three comparative groups of AD versus CHCs, MCI versus CHCs, and AD versus MCI, of which 6 and 5 DMPs were continuously hypermethylated and hypomethylated in MCI and AD relative to CHCs (adjusted p < 0.05), respectively, such as FLNC cg20186636 and AFAP1 cg06758191. The DMPs with an area under the curve >0.900, such as cg18771300, showed high potency for predicting MCI and AD. In addition, gene ontology and pathway enrichment results showed that these overlapping genes were mainly involved in neurotransmitter transport, GABAergic synaptic transmission, signal release from synapse, neurotransmitter secretion, and the regulation of neurotransmitter levels. Furthermore, tissue expression enrichment analysis revealed a subset of potentially cerebral cortex-enriched genes associated with MCI and AD, including SYT7, SYN3, and KCNT1. Conclusion: This study revealed a number of potential biomarkers for MCI and AD, also highlighted the presence of epigenetically dysregulated gene networks that may engage in the underlying pathological events resulting in the onset of cognitive impairment and AD progression. Collectively, this study provides prospective cues for developing therapeutic strategies to improve cognitive impairment and AD course.
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When exposed to various microenvironmental stimuli, macrophages are highly plastic and primarily polarized into the pro-inflammatory M1-type and the anti-inflammatory M2-type, both of which perform almost entirely opposing functions. Due to this characteristic, macrophages perform different functions at different stages of immunity and inflammation. Inflammatory immune skin diseases usually show an imbalance in the M1/M2 macrophage ratio, and altering the macrophage polarization phenotype can either make the symptoms worse or better. Therefore, this review presents the mechanisms of macrophage polarization, inflammation-related signaling pathways (JAK/STAT, NF-κB, and PI3K/Akt), and the role of both in inflammatory immune skin diseases (psoriasis, AD, SLE, BD, etc.) to provide new directions for basic and clinical research of related diseases.
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Small-diameter vascular grafts (SDVGs) cannot meet current clinical demands owing to their suboptimal long-term patency rate. Various materials have been employed to address this issue, including nanomaterials (NMs), which have demonstrated exceptional capabilities and promising application potentials. In this review, the utilization of NMs in different forms, including nanoparticles, nanofibers, and nanofilms, in the SDVG field is discussed, and future perspectives for the development of NM-loading SDVGs are highlighted. It is expected that this review will provide helpful information to scholars in the innovative interdiscipline of cardiovascular disease treatment and NM.