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A palladium-catalyzed domino cyclization/cycloisomerization reaction of alkyne-tethered carbamoyl chlorides with (E)-ß-chloroenones is reported. This reaction proceeds via a syn-carbopalladation of the alkyne, followed by a vinyl-PdII-catalyzed cycloisomerization of the (E)-ß-chloroenone cascade, which provides an efficient method to synthesize furan-linked methylene oxindoles. The reaction features stereodefined vinyl-PdII species, high to excellent 5-exo/6-endo selectivity, excellent Z/E selectivity, and the sequential formation of three bonds and bis-heterocycles. The strategy for the synthesis of furan-containing benzofurans has also been demonstrated.
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Accumulation studies confirmed that oxidative stress caused by ischemia after myocardial infarction (MI) is an important cause of ventricular remodeling. Exosome secretion through hypoxic pretreatment adipose-derived mesenchymal stem cells (ADSCs) ameliorates myocardial damaging post-MI. However, if ADSCs exosome can improve the microenvironment and ameliorate cardiac damage post-MI still unknown. Next-generation sequencing (NGS) was used to study abnormally expressed circRNAs in hypoxic pretreatment ADSC exosomes (HExos) and untreated ADSC exosomes (Exos). Bioinformatics and luciferase reporting were used to elucidate interaction correlation related to circRNA, mRNA, and miRNA. HL-1 cells were used to analyze the reactive oxygen species (ROS) and apoptosis under hypoxic conditions using immunofluorescence and flow cytometry. An MI mouse model was constructed and the therapeutic effect of Exos was determined using immunohistochemistry, immunofluorescence, and ELISA. The results showed that HExos had a more pronounced treatment effect than ADSC Exos on cardiac damage amelioration after MI. NGS showed that circ-Stt3b plays a role in HExo-mediated cardiac damage repair after MI. Overexpression of circ-Stt3b decreased apoptosis, ROS level, and inflammatory factor expression in HL-1 cells under hypoxic conditions. Bioinformatics and luciferase reporting data validated miR-15a-5p and GPX4 as downstream circ-Stt3b targets. GPX4 downregulation or miR-15a-5p overexpression reversed protective effect regarding circ-Stt3b upon HL-1 cells after exposure to a hypoxic microenvironment. Overexpression of circ-Stt3b increased the treatment effect of ASDSC Exos on cardiac damage amelioration after MI. Taken together, the study results demonstrated that Exos from hypoxic pretreatment ADSCs ameliorate cardiac damage post-MI through circ-Stt3b/miR-15a-5p/GPX4 signaling activation and decreased ferroptosis.
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The expression of prostate-specific membrane antigen (PSMA) in prostate cancer is 100-1000 times higher than that in normal tissues, and it has shown great advantages in the diagnosis and treatment of prostate cancer. The combination of PSMA and PET imaging technology based on the principle of metabolic imaging can achieve high sensitivity and high specificity for diagnosis. Due to its suitable half-life (109 min) and good positron abundance (97%), as well as its cyclotron accelerated generation, 18F has the potential to be commercialize, which has attracted much attention. In this article, we synthesized a series of fluorosulfate PET tracers targeting PSMA. All four analogues have shown high affinity to PSMA (IC50 = 1.85-5.15 nM). After the radioisotope exchange labeling, [18F]L9 and [18F]L10 have PSMA specific cellular uptake (0.65 ± 0.04% AD and 1.19 ± 0.03% AD) and effectively accumulated in 22Rv1 xenograft mice model. This study demonstrates that PSMA-1007-based PSMA-targeted aryl [18F]fluorosulfate novel tracers have the potential for PET imaging in tumor tissues.
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Antígenos de Superfície , Desenho de Fármacos , Radioisótopos de Flúor , Tomografia por Emissão de Pósitrons , Compostos Radiofarmacêuticos , Animais , Humanos , Masculino , Radioisótopos de Flúor/química , Camundongos , Antígenos de Superfície/metabolismo , Compostos Radiofarmacêuticos/síntese química , Compostos Radiofarmacêuticos/química , Neoplasias da Próstata/diagnóstico por imagem , Neoplasias da Próstata/metabolismo , Glutamato Carboxipeptidase II/metabolismo , Estrutura Molecular , Linhagem Celular Tumoral , Neoplasias Experimentais/diagnóstico por imagem , Neoplasias Experimentais/metabolismo , Relação Estrutura-AtividadeRESUMO
Our previous study has indicated that tetrandrine (TET) can target miR-202-5p to repress the activation of transient receptor potential vanilloid type 2 (TRPV2), eventually ameliorating the progression of myocardial ischemia/reperfusion injury (MI/RI). This study is aimed to further ascertain the detailed mechanisms between TET and TRPV2 in MI/RI pathogenesis. Here, a myocardial I/R injury rat model and a hypoxia-reoxygenation (H/R) model in rat myocardial cell line (H9C2 cells) were established. We reported that pronounced upregulation of TRPV2 was observed in I/R rats and H/R-induced H9C2 cells. Silencing of TRPV2 could improve cardiac function and myocardial injury, reduced infarction size, and promoted cardiomyocyte proliferation in I/R rats. In I/R rats or H/R-induced H9C2 cells, cardiomyocyte apoptosis was inhibited by knocking-down TRPV2. Meanwhile, the silenced TRPV2 or TET treatment ameliorated the damaged mitochondrial structure, mitigated ROS generation, restored the impaired ΔΨM, inhibited mPTP opening and alleviated Ca2+ overload in H/R-induced H9C2 cells. The results obtained from the overexpression of TRPV2 were contrary to those depicted above. Moreover, TET could downregulate TRPV2 expression, while the overexpression of TRPV2 could reverse the above protective effects of TET in H/R-induced H9C2 cells. The results indicated that TET may function as a TRPV2 blocking agent, thereby attenuating the progression of MI/RI through modulation of cardiomyocyte apoptosis, calcium homeostasis and mitochondrial function. These findings offer a theoretical foundation for potential clinical application of TET therapy in patients with MI/RI.
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Benzilisoquinolinas , MicroRNAs , Traumatismo por Reperfusão Miocárdica , Ratos , Humanos , Animais , Miócitos Cardíacos , Traumatismo por Reperfusão Miocárdica/metabolismo , Cálcio/metabolismo , Apoptose , Mitocôndrias , Hipóxia/metabolismo , Homeostase , MicroRNAs/metabolismo , Canais de Cátion TRPV/genética , Canais de Cátion TRPV/metabolismoRESUMO
OBJECTIVES: The objective of this study was to quantify the morphology, composition, and asymmetry of the paravertebral extensor muscles (PSEMs) in patients with cervical ossification of the posterior longitudinal ligament (OPLL) who had different modified K-line (mK-line) and the minimum interval between the mK-line and OPLL (INTmin ) values and to investigate the relationship between PSEMs and symptoms and outcomes following laminoplasty. These original findings elucidated that the atrophy of PSEMs could predict decompression outcomes and provided a theoretical basis for paraspinal muscle rehabilitation. METHODS: A total of 94 consecutive patients who underwent laminoplasty for OPLL between January 2020 and January 2022 were enrolled in this retrospective study. The relative cross-sectional areas (rCSA), functional cross-sectional areas (rFCSA), and FCSA/CSA ratio of the multifidus (MF), semispinalis cervicalis (SSCe), semispinalis capitis (SSCa), and splenius capitis (SpCa) were measured at the C3-C7 segments on cervical magnetic resonance imaging (MRI). This study compared the differences between the mK-line (+) group and the mK-line (-) group, as well as between the INTmin <4 mm group and the INTmin ≥4 mm group, using the independent t-test or Mann-Whitney test for continuous variables and the χ2 -test for categorical variables. The correlations between the PSEMs and symptoms were analyzed using either the Pearson or Spearman correlation coefficient. RESULTS: The relative total CSA (rTCSA) of the PSEMs, especially the MF, was significantly smaller in the mK-line (-) group. However, the FCSA/CSA of the right deep extensor muscle (DEM) was larger. The asymmetry of the MF TFCSA/TCSA showed a significant difference between the mK-line groups. In the INTmin <4 mm group, the PSEMs rCSA and rFCSA were significantly smaller, while the bilateral MF TFCSA/TCSA and right SSCe TFCSA/TCSA were larger. The asymmetry of the superficial extensor muscle rCSA was significantly lower in the group with INTmin <4 mm. The postoperative modified Japanese Orthopedic Association score (mJOA) and mJOA recovery rate were positively correlated with the INTmin and DEM rCSA and negatively correlated with the asymmetry of MF FCSA/CSA. CONCLUSIONS: In patients with mK-line (-) or INTmin <4 mm, the PSEMs were smaller, and the DEM atrophy and composition changes were predominant. The MF asymmetry was higher in patients with mK-lines (-), whereas the SEM atrophy and asymmetry were more prevalent in patients with INTmin <4 mm. The DEM was related to the preoperative and postoperative mJOA scores. DEM-preserving surgery or DEM-specific rehabilitation exercises can improve the recovery of patients with OPLL during the perioperative period. In addition, attention should be paid to the evaluation of the SEM, especially the SpCa at the C3 and C5 levels.
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Laminoplastia , Ossificação do Ligamento Longitudinal Posterior , Salicilanilidas , Humanos , Ligamentos Longitudinais/cirurgia , Estudos Retrospectivos , Osteogênese , Resultado do Tratamento , Vértebras Cervicais/cirurgia , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Laminoplastia/métodos , Atrofia/etiologiaRESUMO
Background: Analysis of the pathogenic spectrum, epidemiological characteristics and molecular epidemiological features of important pathogens of infectious diarrhea in Yantai City, Shandong Province, 2018-2019, were analyzed to provide a reference basis for the prevention and control of infectious diarrhea. Methods: A total of 1514 stool specimens were collected within 3 days of the onset of diarrhea in secondary or higher hospitals in Yantai from 2018-2019, and all specimens were tested for the presence of seven major viruses and three major bacteria by employing reverse transcription ploymeraer chain reaction (RT-PCR). Population and seasonal analyses were also performed on positive samples for infectious diarrhea. The top two ranked rotavirus and norovirus were focused on genotyping and analysis of geographical distribution. Results: The study showed that the high prevalence of infectious diarrhea in Yantai, Shandong Province, for two consecutive years in 2018 and 2019 was in young children aged 1-5 years, accounting for 48.6% of the total number of cases. Viral diarrhea was distributed throughout the year with no obvious seasonal distribution, while bacterial diarrhea was predominant in summer. Of 1514 stool specimens, the total positive rate of specimens was 43.92% (665/1514). One pathogen was detected in 507 specimens, two pathogens in 107 specimens, and three pathogens in 44 specimens, with mixed infections accounting for 22.71% of positive specimens (151/665). Viral diarrheal pathogens accounted for 93.23% (620/665) of positive samples. The percentages of positive samples for Rotavirus (RV), Norovirus GI, Norovirus GII, Enterovirus universal (EV), Enteroadenovirus (EAdV), Sapovirus (SaV), Astrovirus (Astv), Salmonella (SE), Listeria monocytogenes (LiMo), and Vibrio parahaemolyticus (VP) were 48.57%, 3.61%, 15.34%, and 10.68% of the total positive samples. Conclusions: This study analyzed in detail the composition of infectious diarrhea pathogen spectrum, pathogen alternation pattern, seasonal distribution and population distribution of pathogens in Yantai City, Shandong Province, 2018-2019, to provide a basis for improving relevant local preventive measures and reducing the disease burden.
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Disenteria , Norovirus , Rotavirus , Criança , Humanos , Pré-Escolar , Disenteria/epidemiologia , Diarreia , BactériasRESUMO
Background: Myocardial ischemia/reperfusion (I/R) injury is a severe heart problem resulting from restoring coronary blood flow to the myocardium after ischemia. This study is aimed at ascertaining the therapeutic efficiency and action mechanism of bardoxolone methyl (BARD) in myocardial I/R injury. Methods: In male rats, myocardial ischemia was performed for 0.5 h, and then, reperfusion lasted for 24 h. BARD was administrated in the treatment group. The animal's cardiac function was measured. Myocardial I/R injury serum markers were detected via ELISA. The 2,3,5-triphenyltetrazolium chloride (TTC) staining was used to estimate the infarction. H&E staining was used to evaluate the cardiomyocyte damage, and Masson trichrome staining was used to observe the proliferation of collagen fiber. The apoptotic level was assessed via the caspase-3 immunochemistry and TUNEL staining. Oxidative stress was measured through malondialdehyde, 8-hydroxy-2'-deoxyguanosine, superoxide dismutase, and inducible nitric oxide synthases. The alteration of the Nrf2/HO-1 pathway was confirmed via western blot, immunochemistry, and PCR analysis. Results: The protective effect of BARD on myocardial I/R injury was observed. In detail, BARD decreased cardiac injuries, reduced cardiomyocyte apoptosis, and inhibited oxidative stress. For mechanisms, BARD treatment significantly activates the Nrf2/HO-1 pathway. Conclusion: BARD ameliorates myocardial I/R injury by inhibiting oxidative stress and cardiomyocyte apoptosis via activating the Nrf2/HO-1 pathway.
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Traumatismo por Reperfusão Miocárdica , Ácido Oleanólico , Masculino , Animais , Ratos , Fator 2 Relacionado a NF-E2 , Transdução de SinaisRESUMO
OBJECTIVE: To analyze the relationship between gender, age, and the degree of lumbar degenerative disease. METHODS: 290 patients with Lumbar spinal stenosis and sciatica were analyzed. Sixty patients without sciatica were collected in the control group. Patient demography including age, gender, body mass index (BMI), serum calcium, and triglyceride level was acquired. The cross-sectional area (CSA) and percentage of fat infiltration area (Intermuscular adipose tissue (IMat%) of paraspinal muscles at the L4-5 level were measured using MRI imaging. The patients were divided into five age groups: A (18-30 years old), B (31-40 years old), C (41-50 years old), D (51-60 years old), and E (> 60 years old). Analysis of variance (ANOVA) and LSD was used to analyze differences among subgroups. Student's t-test was used to compare MCSA and fat CSA in the two groups. P < 0.05 was statistically significant. RESULTS: The paraspinal muscle CSA (MCSA) was significantly smaller in women (P < 0.05). Older age was associated with less MCSA and greater fatty infiltration in erector spinae and multifidus (MF) muscle (P < 0.05). Serum calcium and BMI were positively correlated with CSA of erector spinae muscle (P < 0.05), but not with muscle fat infiltration (P > 0.05). Although there was no significant difference in MCSA between the two groups, the fat infiltration (IMat%) in the disease group was significantly higher than in the control group (p < 0.05). CONCLUSION: Lumbar degenerative diseases caused the degeneration of the paravertebral muscles, which mainly resulted in increased intramuscular fat infiltration, rather than changes in the overall MCSA.
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Músculos Paraespinais , Ciática , Humanos , Feminino , Adolescente , Adulto Jovem , Adulto , Pessoa de Meia-Idade , Músculos Paraespinais/diagnóstico por imagem , Músculos Paraespinais/patologia , Cálcio , Vértebras Lombares/diagnóstico por imagem , Atrofia Muscular/patologia , Imageamento por Ressonância Magnética/métodosRESUMO
Introduction: Progressive fibrous dysplasia ossification (FOP) is a rare genetic disease characterized by congenital bone malformations and soft tissue masses that progress to heterotopic ossification. Congenital great toe deformity and progressive heterotopic ossifications with an anatomical and temporal pattern are the two classical clinical characteristics of FOP. We present a unique case of FOP characterized by mandibular angle fascial contracture and back and iliopsoas muscle ossification managed via surgery in a 13 year old girl. Case presentation: A 13 year old girl with a history of right cervical fascial release surgery and back heterotopic osteotomy presented to our clinic due to recurrence of heterotopic ossification, scoliosis, and progressive joint stiffness. Computed tomography (CT) or magnetic resonance imaging (MRI) examination confirmed heterotopic ossification of the left back and left iliopsoas muscle and spinal scoliosis. Two years after the surgery, the patient presented with recurrence of back heterotopic ossification and rapidly advancing ossification of the left iliopsoas muscle. Six months after surgery, the patient had no disability, pain and clinical recurrence, and the joint function recovered. Conclusions: In patients with multiple-site heterotopic ossification caused by FOP, oral function and hip stiffness improve with detailed facial release surgery and rehabilitation treatment. However, dorsal fascia ossification and spinal scoliosis can recur shortly after resection.
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Objective: This study aimed to analyze the risk factors for dysphagia after C1-2 fusion in patients with C1-2 junction diseases. Summary of the background data: Dysphagia is a common postoperative complication of posterior C1-2 junction surgery. The incidence is 9.5% to 26.3%. However, the etiopathogenisis of postoperative dysphagia remains controversial. Methods: This retrospective study included patients who underwent C1-2 fusion from January 2016 to January 2020. The patients were divided into dysphagia group and control group in accordance with the Bazaz R dysphagia scoring system. The patients' age, gender, BMI(body mass index), cause of disease, and changes in the C01cobb, C02cobb, C12cobb, C27cobb, dC02cobb, dC01cobb, dC12cobb, d C27cobb angles before and after operation, were recorded. The parameters and changes were compared to analyze the risk factors for dysphagia after C1-2 fusion. Results: 65 cases (15, with dysphagia; 50, without dysphagia) were included. The incidence of postoperative dysphagia was 23%. The differences in age, gender ratio, and BMI between the two groups were not significant (P > 0.05). The differences among postoperative C12 (29.8° ± 11.24° vs. 20.46° ± 13.39°), postoperative C27cobb (10.56° ± 8.53° vs. 20.21° ± 13.21°), and dC12cobb (9.49° ± 5.16° vs. 1.07° ± 12.44°) between the two groups were significant (P < 0.05). Multiple logistic regression analyses revealed that dC12cobb > 5° was a significant independent risk factor for postoperative dysphagia, And preoperative C27cobb was a preventive factor of postoperative dysphagia. Conclusions: Dysphagia after the C1-2 fusion was common. dC02cobb and dC12cobb were the significant independent risk factors for postoperative dysphagia. Preoperative c27cobb was a preventive factor of dysphagia.
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Introduction: We describe a case of purely extradural spinal meningioma (EDSMs) with nerve root attachment and present the clinical profiles, radiological findings, operative management, and follow-up data, along with a literature review. This case study is purely extradural spinal meningioma attached to the nerve root, and the available literature review discusses the diagnosis and treatment. Purely epidural spinal meningiomas are extremely rare, and only a few clinical reports are published on this disease. Although epidural meningioma is a benign tumor, the recurrence rate is higher when compared with ordinary meningioma. Case study: A 39-year-old male complained of chest and back pain with ring-shaped radiations to the precordial area and numbness in both the lower extremities. After a long walk, he felt disharmony in both his lower limbs. Magnetic resonance imaging showed a mass located on the left posterolateral side of the T1-T3 spinal cord and exhibited a dumbbell-type growth outward at the level of the T2-T3 intervertebral foramen. On the left side of the thoracic, a hemilaminectomy procedure was performed. The tumor was found in the ventral side of the left nerve root of T1 and was surrounded by the left nerve root of T2. To obliterate the tumor, the T2 nerve root was severed. The patient was advised to come for the follow-up on the 3rd, 6th, and 12th months postoperatively, and there were no complaints or signs of recurrence. Conclusion: Purely extradural spinal meningioma with nerve root attachment is rare and has no clinical symptoms and image findings. To completely resect the lesion and avoid recurrence, the affected nerve root, epidural fat tissue, and nerve root sheath should be extensively resected and burned, coagulating the adjacent ventral posterior longitudinal ligament.
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Influential factors of socio-economic and air pollution on life expectancy (LE) show complexity. The investigations of non-linear functions of LE, socio-economic, and air pollution factors have not been largely conducted, and spatial and temporal differences of the linear or non-linear relations between LE and the influential factors have been obscured across countries in the world. In this study, the non-linear relations between LE and factors of per capita gross national income (GNIpc), urban population rate (UPR), and fine-particulate (PM2.5) were estimated from 2000 to 2015 by using a generalized additive model (GAM). The collected data included the 219 countries and regions with sufficient data and covers the period 2000-2015. The results demonstrate that at the global level, the GNIpc plays a stable and significant non-linear role in LE, while the non-linear relationships between UPR, PM2.5, and LE are not significant. The temporal variation was further investigated that the non-linear effect of PM2.5 on LE is gradually strengthened, and the non-linear effect of UPR on LE shows a weakened trend. However, GNIpc always plays a significantly non-linear role in the LE level. Furthermore, the spatial difference in the non-linear relations among different continents is detected. In sum, it cannot be ignored the non-linear effects of socio-economic and air pollution factors on LE at a global scale and across different continents.
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Poluentes Atmosféricos , Poluição do Ar , Poluentes Atmosféricos/análise , Humanos , Renda , Expectativa de Vida , Material Particulado/análise , Fatores Socioeconômicos , População UrbanaRESUMO
Cathepsin D (Cath D) has been evidenced as a potential target for cancer therapy. Our previous studies revealed that TB-9, a tasiamide B derivative, exhibited highly potent inhibition against Cath D with satisfactory selectivity over Cath E and BACE1. But this compound was inactive on cell level possibly due to poor membrane permeability. Herein, we report the design, synthesis, and evaluation of two novel Cath D inhibitors (2 and 3) which combining tasiamide B scaffold with a cell penetrating peptide (CPP) specifically targeting the endolysosomal compartment. The results revealed that 2 and 3 not only retained highly potent inhibition against Cath D, but also were active against MDA-MB-231 cell lines.
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Catepsina D/antagonistas & inibidores , Oligopeptídeos/farmacologia , Inibidores de Proteases/farmacologia , Catepsina D/metabolismo , Permeabilidade da Membrana Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Humanos , Estrutura Molecular , Oligopeptídeos/síntese química , Oligopeptídeos/química , Inibidores de Proteases/síntese química , Inibidores de Proteases/química , Relação Estrutura-AtividadeRESUMO
NLRP3 and PPARγ play important roles in the development of atherosclerosis (AS). Studies have shown that PPARγ regulates the expression of NLRP3 in vascular diseases. In addition, the adipocyte factor CTRP6 can improve the activation of PPARγ in vascular diseases. However, the regulatory relationship between CTRP6, PPARγ, and NLRP3 in AS and its underlying mechanism have not been reported. Since proliferation, migration, and dedifferentiation of vascular smooth muscle cells (VSMCs) are key events in AS, in this study, we induced proliferation, migration, and dedifferentiation of VSCMs through homocysteine (HCY) to detect the specific effects of CTRP6, PPARγ, and NLRP3. Subsequently, CTRP6 was overexpressed and the PPARγ inhibitor GW9662 and agonist rosiglitazone were administered to HCY-induced VSCMs to investigate the mechanisms. The results show that the expression of CTRP6 decreased in HCY-induced VSMCs. In addition, CTRP6 overexpression inhibited the proliferation and migration of HCY-induced VSMCs, as well as cell cycle acceleration and dedifferentiation. Overexpression of CTRP6 increased HCY-induced PPARγ expression and inhibited NLRP3 expression. The addition of GW9662 and rosiglitazone further demonstrated that overexpression of CTRP6 inhibited HCY-induced VSMC proliferation, migration, and dedifferentiation through PPARγ/NLRP3 signaling. In conclusion, CTRP6 inhibited HCY-induced proliferation, migration, and dedifferentiation of VSMCs through PPARγ/NLRP3.
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Colágeno/metabolismo , Homocisteína/metabolismo , Músculo Liso Vascular/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , PPAR gama/metabolismo , Diferenciação Celular , Movimento Celular , Proliferação de Células , Células Cultivadas , Humanos , Músculo Liso Vascular/citologiaRESUMO
Intriguingly, microRNAs (miRs) transferred as cargo in extracellular vesicles (EVs) can modulate wound healing through their regulation of fibroblast functions. In this study, we investigated the effects of miR-106b transfer via EVs derived from human umbilical vein endothelial cells (HUVECs) on skin wound healing. Dual-luciferase reporter gene assay identified that miR-106b could target and inhibit JMJD3. RT-qPCR analysis showed EVs isolated from HUVECs had enriched expression of miR-106b. LL29 fibroblast cells and HaCaT keratinocytes were co-cultured with HUVEC-derived EVs, in which miR-106b had been up-regulated or down-regulated by its mimic or inhibitor. The co-culture with HUVEC-derived EVs increased miR-106b expression, and reduced the viability and adhesion of LL29 and HaCaT cells, whereas the inhibition of miR-106b in HUVEC-derived EVs enhanced the viability and adhesion of LL29 and HaCaT cells through up-regulation of JMJD3. Next, we showed that JMJD3 overexpression enhanced LL29 and HaCaT cell viability and adhesion through elevating RIPK3, which induced the phosphorylation of AKT during the wound-healing process. We next developed a mouse skin wound model to investigate the actions of miR-106b in vivo after 14 days. The delivery of miR-106b via HUVEC-derived EVs delayed wound healing through suppression of collagen I content and angiogenesis, but had no effects on pro-inflammatory cytokines. In conclusion, miR-106b from HUVEC-derived EVs inhibits JMJD3 and RIPK3, leading to the inhibition of skin wound healing, thus constituting a new therapeutic target.
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Vesículas Extracelulares/patologia , Fibroblastos/patologia , Queratinócitos/patologia , MicroRNAs/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Pele/patologia , Cicatrização , Animais , Proliferação de Células , Células Cultivadas , Vesículas Extracelulares/metabolismo , Fibroblastos/metabolismo , Regulação da Expressão Gênica , Células Endoteliais da Veia Umbilical Humana , Humanos , Histona Desmetilases com o Domínio Jumonji , Queratinócitos/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Pele/metabolismoRESUMO
Paeoniflorin (PF) has been demonstrated to exert tumor suppressive functions in various types of human cancer. However, the mechanisms of PF-mediated anti-tumor activity have not been fully elucidated. S-phase kinase associated protein 2 (Skp2) has been characterized as an oncoprotein that contributes to carcinogenesis. Therefore, the inhibition of Skp2 may be a useful approach for the treatment of various types of human cancer. The present study explored whether PF inhibited the expression of Skp2 in liver cancer cells, leading to cell viability inhibition, induction of apoptosis, and suppression of migration and invasion. PF treatment led to inhibition of Skp2 expression in liver cancer cells. The overexpression of Skp2 abolished PF-mediated anti-cancer activity, whereas the downregulation of Skp2 enhanced this type of activity. The data indicated that PF may be considered as a novel inhibitor of Skp2 in liver cancer cells.
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Unintentional injuries pose a great risk for human health in China. Few studies have focused on unintentional injuries at national level from urbanization perspective. The panel data of mortality rate of transportation accidents (TA), fall and drowning and sinking (DS) is investigated, and urbanization development index is collected. Global Moran's I and linear regression of panel data are applied to determine the spatial distribution and spatial influencing factors of unintentional injuries. The results are the following: (1) The unintentional injury such as TA, fall, and DS shows clear non-uniformity of spatial distribution and relative immobility through time. (2) A 10,000 tons increase in SO2 emission amount (SO2 EA) and emission of smoke and dust (ESD) can result in 15.7 and 12.5 increases in TA death in eastern region, respectively. Meanwhile, A 10,000 tons increase in NOx emission amount can cause 15.1 increase in TA death in western region. For every 100 billion yuan increase in GDP, the fall death can reduce by 8.4 in central region. One bed increase in number of hospital beds per 10,000 population (NHBP) is favorable for decreasing in fall death by 16.7 in eastern region. However, increase in number of workers enjoying industrial injury (NEWII) does not reduce the fall death in eastern region. (3) For every 1 ten thousand people increase in number of students in ordinary high schools (NSOHS) is conductive to reducing DS death by 7.8 in the western region. Our findings show that there exist spatial differences for urbanization influencing TA, fall, and DS death in eastern, western, and central regions. This study is expected to provide a reference for unintentional injuries control in those three regions.
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Lesões Acidentais/mortalidade , Acidentes , China , Humanos , Análise Espaço-Temporal , Urbanização/tendências , Ferimentos e Lesões/mortalidadeRESUMO
BACKGROUND Vitamin D insufficiency is widespread in China. Various factors influence vitamin D level in the body. The present study investigated vitamin D status of residents in Jinzhong city, China, and analyzed the influence of gender on vitamin D status. MATERIAL AND METHODS In this cross-sectional study, 302 participants (176 men and 126 women) were recruited. Anthropometric data (body circumferences and height, weight) were collected, and serum vitamin D concentration was tested. RESULTS Inadequate levels of vitamin D were found in 69% of men and 75% of women. Women's 25(OH)D level (38.40±12.37 nmol/l) was substantially lower than that of the men (43.49±14.78 nmol/l) (p<0.01). The young women group had the lowest vitamin D level, which was even significantly below that of the elderly women group. Multiple linear regression analysis showed gender was significantly associated with vitamin D status (p<0.01). CONCLUSIONS Vitamin D deficiency is common in residents of Jinzhong during the winter. Compared to men, women are more prone to have inadequate vitamin D levels.