RESUMO
AIM: To investigate the impact of hsa_circ_0007482 on the proliferation and apoptosis of human pterygium fibroblasts (HPFs) and its correlation with the severity grades of pterygium. METHODS: Pterygium and normal conjunctival tissues were collected from the superior area of the same patient's eye (n=33). The correlation between pterygium severity and hsa_circ_0007482 expression using quantitative reverse-transcription polymerase chain reaction (RT-qPCR) were analyzed. Three distinct siRNA sequences targeting hsa_circ_0007482, along with a negative control sequence, were transfected into HPFs. Cell proliferation was assessed using the cell counting kit-8. Expression levels of Ki67, proliferating cell nuclear antigen (PCNA), Cyclin D1, Bax, B-cell lymphoma-2 (Bcl-2), and Caspase-3 were measured via RT-qPCR. Immunofluorescence staining was employed to detect Ki67 and vimentin expressions. Apoptosis was evaluated using flow cytometry. RESULTS: Hsa_circ_0007482 expression was significantly higher in pterygium tissues compared to normal conjunctival tissues (P<0.001). Positive correlations were observed between hsa_circ_0007482 expression and pterygium severity, thickness, and vascular density. Knockdown of hsa_circ_0007482 inhibited cell proliferation, reducing the mRNA expression of Ki67, PCNA, and Cyclin D1 in HPFs. Hsa_circ_0007482 knockdown induced apoptosis, increasing mRNA expression levels of Bax and Caspase-3, while decreasing Bcl-2 expression in HPFs. Additionally, hsa_circ_0007482 knockdown attenuated vimentin expression in HPFs. CONCLUSION: The downregulation of hsa_circ_0007482 effectively hampers cell proliferation and triggers apoptosis in HPFs. There are discernible positive correlations detected between the expression of hsa_circ_0007482 and the severity of pterygium.
RESUMO
Under the "dual-carbon" strategic goals, it is urgent to examine whether the energy consumption permit trading scheme ï¼ECPTSï¼, as an innovative system in China's market-oriented reform of the energy sector, can promote the synergistic enhancement of pollution reduction and carbon abatement. Based on provincial panel data of China from 2008 to 2019, this study adopted a difference-in-differences model to examine the impacts of the ECPTS on the synergistic enhancement of pollution reduction and carbon abatement. The results demonstrated that the ECPTS improved the level of pollution reduction and carbon abatement in pilot areas. Specifically, the ECPTS led to a reduction of 13.3% in CO2 emissions and 3.1% in PM2.5 concentration in the pilot areas and resulted in an overall improvement of pollution reduction and carbon abatement by 0.237 units. Mechanism analysis revealed that energy efficiency served as a pathway through which the ECPTS empowered the synergistic enhancement of pollution reduction and carbon abatement. Moreover, the strengthening of local government environmental protection goals enhanced the pollution reduction and carbon abatement effects of the ECPTS. Surprisingly, the effectiveness of the ECPTS was not undermined by the goal of economic growth. This study provides new empirical evidence for understanding the relationship between market-based environmental regulation and collaborative governance and provides strong support for China to achieve its "dual-carbon" strategic goals.
RESUMO
OBJECTIVE: To compare the posterior cruciate ligament(PCL) index with six different measurement methods, and analyze and verify its clinical diagnostic value in anterior cruciate ligament (ACL) injury. METHODS: The Magnetic resonance imaging (MRI) data of 225 knee joints in our hospital from May 2018 to March 2022 were retrospectively analyzed, aged from 18 to 60 years old, with a median of 32 years old. On the sagittal MRI images of 114 patients with ACL injury and 111 patients with intact ACL, Measure the straight-line distance (A) between the femoral attachment point and the tibial attachment point of the PCL on the MRI sagittal image and the maximum vertical distance (B) between the straight line and the arcuate mark point of the PCL on the sagittal image, calculate the PCL index and evaluate the diagnostic value of the PCL index for ACL injury. RESULTS: The PCL index of the ACL normal group and the ACL injury group were statistically described. There was no significant difference in PCL index 1, 2, 3 and 6 between the two groups(P>0.05). The difference of PCL index 4 and 5 between the two groups was statistically significant (P<0.001). This study only found that the PCL index 2, 6 in the ACL normal group had a negative correlation with the patient's age (correlation coefficient=-0.213, -0.819;P<0.05), and the PCL index 5 in the ACL injury group was significantly correlated with the patient's body mass index(BMI)had a negative correlation (correlation coefficient=-0.277, P<0.05). CONCLUSION: The change of PCL index is helpful for the diagnosis of ACL injury, PCL index 4 and 5 can be used as effective reference indexes for diagnosing ACL injury in clinic.
Assuntos
Lesões do Ligamento Cruzado Anterior , Ligamento Cruzado Posterior , Humanos , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Ligamento Cruzado Posterior/diagnóstico por imagem , Lesões do Ligamento Cruzado Anterior/diagnóstico por imagem , Ligamento Cruzado Anterior , Estudos Retrospectivos , Articulação do Joelho , Imageamento por Ressonância Magnética/métodosRESUMO
BACKGROUND: Peutz-Jeghers syndrome (PJS) is a rare autosomal dominant disorder, and female patients may develop gynecologic tumours. The prognosis for such patients is poor and the specific pathogenesis remains uncertain. Therefore, there are currently no uniform treatment options. CASE SUMMARY: Herein, we introduce the case of a 45-year-old female who was diagnosed with PJS for 45 years and cervical cancer for 3 years. Postoperative pathological examination showed metastases in the right external iliac lymph nodes. The patient was initially treated with a combination of doxorubicin and carboplatin chemotherapy and pelvic magnetic resonance showed that the metastases had grown. Subsequently, we performed whole exome sequencing in this patient and identified the relevant causative gene. In addition to the chemotherapy regimen, sindilizumab was administered and the patient was followed up. After 4 cycles of treatment, the metastases were substantially reduced and were not enlarged after six months of follow-up. This case report suggests that patients with PJS combined with cervical cancer may have a sustained response to immune-combination chemotherapy regimens. CONCLUSION: Clinicians should be aware of the importance of immunotherapy in patients with PJS combined with advanced cervical cancer.
RESUMO
Tetrapanax papyriferus is an evergreen shrub native to China and traditionally used as a herbal medicine (Li et al., 2021). In September 2021, a serious leaf spot disease with symptoms similar to anthracnose was extensively observed on T. papyriferus in Shibing county (E 127°12'0", N 25°11'60"), Qiandongnan Miao and Dong Autonomous Prefecture, Guizhou province, China. Field surveys were conducted in about 1000 T. papyriferus plants in Shibing in September 2021. The incidence of the leaf spot on leaves was 45% to 60%, significantly reducing the quality of medicinal materials. The symptoms began as small yellow spots, developing a brown center and dark brown to black margin, and eventually the diseased leaves were wiltered and rotted. Symptomatic leaves were collected from 20 trees. Symptomatic tissue from diseased leaves was surface desinfected (0.5 min in 75% ethanol and 1 min in 3% NaOCl, washed three times with sterilized distilled water), small pieces of symptomatic leaf tissue (0.2 × 0.2 cm) were plated on potato dextrose agar (PDA) and incubated at 25°C for about 7 days (Fang. 2007). Three single-spore isolates were obtained (GUTC37, GUTC310 and GUTC311) and deposited in the collection of the Plant Pathology Deparment, College of Agriculture, Guizhou University, China (GUCC) (with the accession numbers, GUCC220241, GUCC220242, GUCC220243 respectively). These isolates were identical in morphology and in the sequences of internal transcribed spacer region [ITS], glyceraldehy-3-phosphate dehydrogenase [GAPDH], chitin synthase [CHS-1], actin [ACT], and calmodulin [CAL] genes (White et al. 1990; Carbone and Kohn 1999; Templeton et al. 1992). Therefore, the representative isolate GUTC37 was used for further analysis. The pathogenicity of GUTC37 was tested through a pot assay. Plants were inoculated by spraying a spore suspension (106 spores·ml-1) of isolated strains onto leaves until runoff, and the control leaves sprayed with sterile water. The inoculated plants were incubated in a growth chamber at 28 â and 95% relative humidity for 10 days. Pathogenicity tests were repeated three times (Fang. 2007). The symptoms developed on the inoculated leaves, while control remained asymptomatic. The lesions were first visible 72 h after inoculation, and typical lesions like those observed on field plants appeared after 10 days. The same fungus was reisolated and identified based on the morphological characterization and molecular analyses from the infected leaves but not from the non-inoculated leaves. Results of pathogenicity experiments of isolated fungi fulfilled Koch's postulates. Fungal colonies on PDA were villiform, creamy-white or greyish, aerial mycelium pale grey, dense, surface partly covered with orange conidial masses. The conidia were abundant, oval-ellipsoid, aseptate, and 13.89 (11.62 to 15.21) × 5.21 (4.39 to 5.65) µm (n=50). Appressorium were greyish green, nearly ovoid to cylindrical, 9.64 (6.62 to 14.61) × 6.33 (5.45-7.72) µm (n=50). The morphological features were consistent with the descriptions of Colletotrichum fructicola Prihast., L. Cai & K.D. Hyde (Prihastuti et al. 2009). The pathogen was identified to be C. fructicola by amplification and sequencing of the five genes. The sequences of the PCR products were deposited in GenBank with accession numbers OP143657 (ITS), OP177868 (GAPDH), OP177865 (CHS-1), OP278677 (ACT) and OP177862 (CAL). BLAST searches of the obtained sequences revealed 100% (509/509 nucleotides), 99.63% (269/270 nucleotides), 99.31% (287/289 nucleotides), 99.29% (280/282 nucleotides), and 99.86% (728/729 nucleotides) homology with those of C. fructicola in GenBank (JX010165, JX010033, JX009866, FJ907426, and JX009676, respectively). Phylogenetic analysis (MEGA 7.0) using the maximum likelihood method placed the isolate GUTC37 in a well-supported cluster with C. fructicola. To our knowledge, this is the first report of anthracnose on T. papyriferus caused by C. fructicola in Guizhou, China. This study provides valuable information for the identification and control of the anthracnose on T. papyriferus.
RESUMO
The limited cardiomyocyte proliferation is insufficient for repair of the myocardium. Therefore, activating cardiomyocyte proliferation might be a reasonable option for myocardial regeneration. Here, we investigated effect of retinoic acid (RA) on inducing adult cardiomyocyte proliferation and assessed efficacy of self-assembling peptide (SAP)-released RA in activating regeneration of the infarcted myocardium. Effect of RA on inducing cardiomyocyte proliferation was examined with the isolated cardiomyocytes. Expression of the cell cycle-associated genes and paracrine factors in the infarcted myocardium was examined at one week after treatment with SAP-carried RA. Cardiomyocyte proliferation, myocardial regeneration and improvement of cardiac function were assessed at four weeks after treatment. In the adult rat myocardium, expression of RA synthetase gene Raldh2 and RA concentration were decreased significantly. After treatment with RA, the proliferated cardiomyocytes were increased. The formulated SAP could sustainedly release RA. After treatment with SAP-carried RA, expression of the pro-proliferative genes in cell cycle and paracrine factors in the infarcted myocardium were up-regulated. Myocardial regeneration was enhanced, and cardiac function was improved significantly. These results demonstrate that RA can induce adult cardiomyocytes to proliferate effectively. The sustained release of RA with SAP is a promise strategy to enhance repair of the infarcted myocardium.
Assuntos
Infarto do Miocárdio , Miócitos Cardíacos , Ratos , Animais , Miócitos Cardíacos/metabolismo , Infarto do Miocárdio/metabolismo , Tretinoína/farmacologia , Tretinoína/metabolismo , Miocárdio/metabolismo , Peptídeos/farmacologia , Peptídeos/metabolismo , Proliferação de CélulasRESUMO
Objective To investigate the effect of dual-specificity phosphatase 1/optical atrophy 1 (DUSP1/OPA1) signaling pathway on vascular smooth muscle cell (VSMC) calcification.Methods An in vitro model of VSMC calcification was induced by exposure to ß-glycerophosphate and calcium chloride.VSMC calcification was assessed by Alizarin Red S staining and calcium content by ELISA.Apoptosis was detected by TUNEL.Western blotting was employed to determine the protein levels of DUSP1,OPA1,Runt-related transcription factor 2 (Runx-2),bone morphogenetic protein 2 (BMP-2),and cysteinyl aspartate-specific proteinase-3 (Caspase-3).The effects of DUSP1 overexpression and OPA1 knockdown on cell calcification were investigated.Results Calcium chloride and ß-glycerolphosphate induced VSMC calcification and down-regulated the expression levels of DUSP1 (t=11.951,P<0.001) and OPA1 (t=8.487,P<0.001).DUSP1 overexpression promoted OPA1 expression (t=-8.921,P<0.001),attenuated VSMC calcification,reduced calcium content and apoptosis rate,and down-regulated the expression of Runx-2,BMP-2,and active Caspase-3 (all P<0.001).OPA1 knockdown increased calcium content and apoptosis rate,up-regulated the expression of Runx-2,BMP-2,and active Caspase-3,and promoted VSMC calcification (all P<0.001).Conclusion DUSP1 may inhibit the VSMC calcification through the OPA1 signaling pathway.
Assuntos
Calcinose , Músculo Liso Vascular , Atrofia/metabolismo , Atrofia/patologia , Cálcio/metabolismo , Cloreto de Cálcio/metabolismo , Caspase 3/metabolismo , Fosfatases de Especificidade Dupla/metabolismo , Humanos , Músculo Liso Vascular/metabolismo , Músculo Liso Vascular/patologiaRESUMO
The epicardium plays an important role in cardiomyogenesis during development, while it becomes quiescent in adult heart during homeostasis. This study investigates the efficiency of thymosin ß4 (Tß4) release with RPRHQGVM conjugated to the C-terminus of RADA16-I (RADA-RPR), the functionalized self-assembling peptide (SAP), to activate the epicardium and repairing the infarcted myocardium. Methods: The functionalized SAP was constituted with self-assembling motif, Tß4-binding site, and cell adhesive ligand. Myocardial infarction (MI) models of the transgenic mice were established by ligation of the left anterior descending coronary artery. At one week after intramyocardial injection of Tß4-conjugated SAP, the activation of the epicardium was assessed. At four weeks after implantation, the migration and differentiation of epicardium-derived cells (EPDCs) as well as angiogenesis, lymphangiogenesis and myocardial regeneration were examined. Results: We found that the designer RADA-RPR bound Tß4 and adhered to EPDCs and that Tß4 released from the functionalized SAP could effectively activate the epicardium and induce EPDCs to differentiate towards cardiovascular cells as well as lymphatic endothelial cells. Moreover, SAP-released Tß4 (SAP-Tß4) promoted proliferation of cardiomyocytes. Furthermore, angiogenesis, lymphangiogenesis and myocardial regeneration were enhanced in the MI models at 4 weeks after delivery of SAP-Tß4 along with attenuation of adverse myocardial remodeling and significantly improved cardiac function. Conclusions: These results demonstrate that sustained release of Tß4 from the functionalized SAP can activate the epicardium and effectively enhance the repair of infarcted myocardium. We believe the delivery of SAP-Tß4 may be a promising strategy for MI therapy.
Assuntos
Infarto do Miocárdio/tratamento farmacológico , Miocárdio/patologia , Peptídeos/farmacologia , Pericárdio/efeitos dos fármacos , Timosina/farmacologia , Animais , Diferenciação Celular/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Endoteliais/efeitos dos fármacos , Linfangiogênese/efeitos dos fármacos , Camundongos , Camundongos Transgênicos , Miocárdio/metabolismo , Miócitos Cardíacos/efeitos dos fármacos , Neovascularização Fisiológica/efeitos dos fármacosRESUMO
Sepsis-induced multiple organ dysfunction and inflammatory response are life-threatening symptoms without effective treatment. Fisetin, a dietary flavonoid extracted from berries and family Fabaceae, has displayed neuroprotective and anti-oxidant activities. In this study we investigated whether fisetin exerted a protective effect against sepsis-induced multiple organ dysfunction in mouse cecum ligation and puncture (CLP) model. The mice were injected with fisetin (10 mg/kg, ip) 0.5 h prior to CLP, and sacrificed 18 h after CLP. We found that fisetin administration significantly alleviated CLP-induced lung, liver and kidney injury, as well as the expression levels of interleukin (IL)-6, tumor necrosis factor (TNF)-α and IL-1ß in bronchoalveolar lavage fluid (BALF). In lipopolysaccharide (LPS)-treated mouse bone marrow-derived macrophages (BMDMs), application of fisetin (3-10 µM) dose-dependently inhibited the expression levels of IL-6, TNF-α, IL-1ß, and inducible nitric oxide synthase (iNOS). Furthermore, fisetin dose-dependently inhibited the phosphorylation of p38 MAPK, MK2, and transforming growth factor-ß-activated kinase (TAK) 1 via attenuating the interaction between TAK1 and TAK-binding proteins (TAB) 1. These results demonstrate that fisetin is a promising agent for protecting against sepsis-induced inflammatory response and organ injury via inhibiting macrophage activation.
Assuntos
Flavonóis/uso terapêutico , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Insuficiência de Múltiplos Órgãos/prevenção & controle , Substâncias Protetoras/uso terapêutico , Animais , Ceco/cirurgia , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Rim/patologia , Fígado/patologia , Pulmão/patologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos C57BL , Insuficiência de Múltiplos Órgãos/epidemiologia , Insuficiência de Múltiplos Órgãos/patologia , Subunidade p50 de NF-kappa B/metabolismo , Óxido Nítrico/metabolismo , Óxido Nítrico Sintase Tipo II/metabolismo , Sepse/complicaçõesRESUMO
OBJECTIVE: To study whether the two methods of energy calculation affects the value of relative energy contribution in men's T54 wheelchair racing events. METHODS: Ten men's T54 wheelchair racers (age (22.9±5.2) yrsãsitting height (90.9±3.2) cmãbody mass (59.3±8.3) kg) participate in 1 incremental test and 4 time trials (400 mã800 mã1 500 mã5 000 m). A portable gas analyzer, polar heart rate belt and a blood lactate analyzer were used to measure VO2 at every breath, HR and blood lactate changes. The energetic contribution was measured with phosphocreatine-lactate-oxygen(PCr-La-O2) and maximal accumulated oxygen deficit(MAOD) methods. RESULTS: The anaerobic and total energy portions from MAOD were lower than those from PCr-La-O2 ( especially in 400 m: WTOT (50.8 ±12.7) KJ vs (65.2±13.5) KJãWANA (31.0±9.0) KJ vs (45.4±11.4) KJ, Pï¼0.05), resulting in WAER% calculated by MAOD was generally higher than PCr-La-O2 method (especially in 400 m : WAER% 39.0% ±1.2% vs 30.4%±8.4 %,Pï¼0.05). CONCLUSION: The study proves that the two-calculation method causes WAER% difference. MAOD method does lead to an overestimate of WAER%. Recommend to use the same calculation method for diagnosis and monitoring in the longitudinal study of long-term scientific research (such as the 4-year Olympic Games),to avoiding the difference in results caused by different calculation methods, which will further influence the development of coaches' training plans and training implementation effect.
Assuntos
Metabolismo Energético , Consumo de Oxigênio , Esportes para Pessoas com Deficiência , Cadeiras de Rodas , Teste de Esforço , Humanos , Ácido Láctico , MasculinoRESUMO
Mitochondrial fission plays a role in cardiovascular calcification. Melatonin has previously been shown to protect against cardiovascular disease, so this study sought to explore whether it attenuates vascular calcification by regulating mitochondrial fission via the AMP-activated protein kinase/dynamin-related protein 1 (AMPK/Drp1) signalling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin red staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure the expression of runt-related transcription factor 2 (Runx2), Drp1 and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were down-regulated, Drp1 was reduced in response to melatonin, and this was accompanied by decreased apoptosis. Melatonin also reduced levels of mitochondrial superoxide, reversed ß-glycerophosphate (ß-GP)-induced ΔΨm dissipation and decreased mitochondrial fragmentation. The effects of melatonin in ß-GP-treated VSMCs were similar to those of mitochondrial division inhibitor 1. Melatonin significantly activated the expression of AMPK and decreased Drp1 expression. Treatment with compound C ablated the observed benefits of melatonin treatment. These findings indicate that melatonin protects VSMCs against calcification by inhibiting mitochondrial fission via the AMPK/Drp1 pathway.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Dinaminas/metabolismo , Melatonina/farmacologia , Dinâmica Mitocondrial/efeitos dos fármacos , Transdução de Sinais , Calcificação Vascular/metabolismo , Proteínas Quinases Ativadas por AMP/antagonistas & inibidores , Animais , Apoptose/efeitos dos fármacos , Cálcio/metabolismo , Citoproteção/efeitos dos fármacos , Glicerofosfatos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Modelos Biológicos , Músculo Liso Vascular/patologia , Miócitos de Músculo Liso/metabolismo , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Superóxidos/metabolismo , Calcificação Vascular/patologiaRESUMO
Mitochondrial fusion/mitophagy plays a role in cardiovascular calcification. Melatonin has been shown to protect against cardiovascular disease. This study sought to explore whether melatonin attenuates vascular calcification by regulating mitochondrial fusion/mitophagy via the AMP-activated protein kinase/optic atrophy 1 (AMPK/OPA1) signaling pathway. The effects of melatonin on vascular calcification were investigated in vascular smooth muscle cells (VSMCs). Calcium deposits were visualized by Alizarin Red S staining, while calcium content and alkaline phosphatase (ALP) activity were used to evaluate osteogenic differentiation. Western blots were used to measure expression of runt-related transcription factor 2 (Runx2), mitofusin 2 (Mfn2), mito-light chain 3 (mito-LC3) II, and cleaved caspase 3. Melatonin markedly reduced calcium deposition and ALP activity. Runx2 and cleaved caspase 3 were downregulated in response to melatonin, whereas Mfn2 and mito-LC3II were enhanced and accompanied by decreased mitochondrial superoxide levels. Melatonin also maintained mitochondrial function and promoted mitochondrial fusion/mitophagy via the OPA1 pathway. However, OPA1 deletion abolished the protective effects of melatonin on VSMC calcification. Melatonin treatment significantly increased p-AMPK and OPA1 protein expression, whereas treatment with compound C ablated the observed benefits of melatonin treatment. Collectively, our results demonstrate that melatonin protects VSMCs against calcification by promoting mitochondrial fusion/mitophagy via the AMPK/OPA1 pathway.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Antioxidantes/uso terapêutico , Cálcio/metabolismo , GTP Fosfo-Hidrolases/efeitos dos fármacos , Melatonina/uso terapêutico , Dinâmica Mitocondrial/efeitos dos fármacos , Mitofagia/efeitos dos fármacos , Animais , Antioxidantes/farmacologia , Modelos Animais de Doenças , Humanos , Melatonina/farmacologia , Músculo Liso Vascular , Ratos , Ratos Sprague-DawleyRESUMO
Serelaxin, a recombinant form of human relaxin-2, is currently regarded as a novel drug for treatment of acute heart failure. However, whether therapeutic effects of serelaxin are achieved by inhibiting cardiac fibrosis remains unclear. In this study, we investigate effects of serelaxin on inhibiting cardiac fibrosis. Cardiac fibroblasts (CFs) were isolated from the hearts of adult rats. Effects of serelaxin on differentiation of CFs towards myofibroblasts (MFs) and their fibrotic behaviors after induction with TGF-ß1 were examined. Synthesis and degradation of collagens, secretion of IL-10, and expression of ALK-5 and p-Smad2/3 of TGF-ß1-induced cells were assessed after treatment with serelaxin. Serelaxin inhibited differentiation of TGF-ß1-induced CFs towards MFs, and reduced proliferation and migration of the induced cells. Moreover, serelaxin down-regulated expression of collagen I/III and TIMP-2, and up-regulated expression of MMP-2 and MMP-9 in the cells. After treatment with serelaxin, activity of MMP-2 and MMP-9 and secretion of IL-10 increased, expression of ALK-5 and the level of Smad2/3 phosphorylation was reduced significantly. These results suggest that serelaxin can inhibit differentiation of TGF-ß1-induced CFs towards MFs, reduce production of collagens by suppressing ALK-5/Smad2/3 signaling pathway, and enhance extracellular matrix degradation by increasing MMP-2/TIMP-2 ratio and IL-10 secretion. Serelaxin may be a potential therapeutic drug for inhibiting cardiac fibrosis.
Assuntos
Diferenciação Celular/efeitos dos fármacos , Miocárdio/patologia , Miócitos Cardíacos/efeitos dos fármacos , Miofibroblastos/efeitos dos fármacos , Relaxina/farmacologia , Animais , Células Cultivadas , Regulação para Baixo/efeitos dos fármacos , Feminino , Fibrose/metabolismo , Fibrose/prevenção & controle , Humanos , Miocárdio/metabolismo , Miócitos Cardíacos/patologia , Miócitos Cardíacos/fisiologia , Proteínas Serina-Treonina Quinases/metabolismo , Ratos , Ratos Sprague-Dawley , Receptor do Fator de Crescimento Transformador beta Tipo I , Receptores de Fatores de Crescimento Transformadores beta/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de Sinais/efeitos dos fármacos , Proteína Smad2/metabolismo , Proteína Smad3/metabolismoRESUMO
The aim of this paper is to investigate the topical pharmacodynamics behavior of different lipophilic model drugs after treatment with essential oil from Zanthoxyli Pericarpium by using the cutaneous microdialysis technique, and then evaluate its in vivo transdermal penetration enhancing properties. Two traditional Chinese medicine active components, namely tetramethylpyrazine and puerarin, were chosen as lipophilic and hydrophilic model drugs, respectively. Firstly, the concentration difference method was employed to measure the in vitro recovery rate and loss of the microdialysis probe, and the in vivo recoveries of two model drugs were determined by using the retrodialysis method. Secondly, the skin pharmacodynamics behaviors of two model drugs were studied after treatment with different concentrations of the essential oil, and the well-established and standard penetration enhancer Azone was selected as a positive control. It was found that the recovery of microdialysis probe was equal to its loss for two model drugs, with no interaction between drugs in dialysis membranes. The retrodialysis studies revealed that the in vivo recovery of tetramethylpyrazine and puerarin were 59.17%, 19.85%, respectively. The skin pharmacodynamics studies showed that the essential oil could facilitate the transdermal absorption of tetramethylpyrazine in a concentration-dependent manner, and the enhancement ratio (ER) for 5% essential oil was 98.64, which was higher than that of the optimum concentration of Azone (3% Azone, ER=89.11). Meanwhile, the Zanthoxyli Pericarpium could effectively promote the transdermal permeation of the puerarin in a concentration-dependent manner. Hence, this study further confirmed that the Zanthoxyli Pericarpium had excellent penetration-enhancing activity as a natural transdermal penetration enhancer, providing data support for its application in traditional Chinese medicine external preparations.
Assuntos
Medicamentos de Ervas Chinesas/administração & dosagem , Óleos Voláteis/administração & dosagem , Óleos de Plantas/administração & dosagem , Absorção Cutânea , Zanthoxylum/química , Administração Cutânea , Microdiálise , PeleRESUMO
Cardiac patch is considered a promising strategy for enhancing stem cell therapy of myocardial infarction (MI). However, the underlying mechanisms for cardiac patch repairing infarcted myocardium remain unclear. In this study, we investigated the mechanisms of PCL/gelatin patch loaded with MSCs on activating endogenous cardiac repair. PCL/gelatin patch was fabricated by electrospun. The patch enhanced the survival of the seeded MSCs and their HIF-1α, Tß4, VEGF and SDF-1 expression and decreased CXCL14 expression in hypoxic and serum-deprived conditions. In murine MI models, the survival and distribution of the engrafted MSCs and the activation of the epicardium were examined, respectively. At 4 weeks after transplantation of the cell patch, the cardiac functions were significantly improved. The engrafted MSCs migrated across the epicardium and into the myocardium. Tendency of HIF-1α, Tß4, VEGF, SDF-1 and CXCL14 expression in the infarcted myocardium was similar with expression in vitro. The epicardium was activated and epicardial-derived cells (EPDCs) migrated into deep tissue. The EPDCs differentiated into endothelial cells and smooth muscle cells, and some of EPDCs showed to have differentiated into cardiomyocytes. Density of blood and lymphatic capillaries increased significantly. More c-kit+ cells were recruited into the infarcted myocardium after transplantation of the cell patch. The results suggest that epicardial transplantation of the cell patch promotes repair of the infarcted myocardium and improves cardiac functions by enhancing the survival of the transplanted cells, accelerating locality paracrine, and then activating the epicardium and recruiting endogenous c-kit+ cells. Epicardial transplantation of the cell patch may be applied as a novel effective MI therapy.
Assuntos
Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais/citologia , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Miocárdio/patologia , Regeneração , Animais , Materiais Biocompatíveis/química , Capilares/patologia , Diferenciação Celular/genética , Sobrevivência Celular/genética , Quimiocinas/metabolismo , Citoproteção , Gelatina/química , Regulação da Expressão Gênica , Testes de Função Cardíaca , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Linfangiogênese/genética , Masculino , Células-Tronco Mesenquimais/ultraestrutura , Camundongos , Infarto do Miocárdio/fisiopatologia , Neovascularização Fisiológica , Poliésteres/química , Proteínas Proto-Oncogênicas c-kit/metabolismo , Ratos Sprague-Dawley , Timosina/metabolismo , Fator A de Crescimento do Endotélio Vascular/metabolismoRESUMO
Through a three-year field trail, effects of deep plowing time during the fallow period on water storage of 0-200 cm soil before sowing, water consumption of growth period, and growth and development of wheat were investigated. Results demonstrated that soil water storage (SWS) of the fallow period was influenced by deep plowing time, precipitation, and rainfall distribution. With postponing the time of deep plowing in the fallow period, SWS was increased firstly, and then decreased. SWS with deep plowing in early or middle of August was 23.9-45.8 mm more than that with deep plowing in mid-July. It would benefit SWS when more precipitation occurred in the fallow period or more rainfall was distributed in August and September. Deep plowing at a proper time could facilitate SWS, N and P absorption of wheat, and the number of stems before winter and the spike number. The yield of wheat with deep plowing in early or middle August was 3.67%-18.2% higher than that with deep plowing in mid-July, and it was positively correlated with water storage of 0-200 cm soil during the fallow period and SWS of each soil layer during the wheat growth period. However, this correlation coefficient would be weakened by adequate rainfall in spring, the critical growing period for wheat. The time of deep plowing mainly affected the water consumption at soil layer of 60-140 cm during wheat growth. Under current farming conditions of south Shanxi, the increased grain yield of wheat could be achieved by combining the measures of high wheat stubble and wheat straw covering for holding soil water and deep plowing between the Beginning of Autumn (August 6th) and the Limit of Heat (August 21st) for promoting soil water penetration characteristics to improve the number of stems before winter and spike.