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Three series of benzoheterocyclic-substituted amide derivatives were designed and synthesized as potent ASK1 inhibitors in this work. After undergoing continuous structural optimization, compound 17a was discovered to be a novel inhibitor of ASK1 with good potency (kinase, IC50 = 26 nM), noteworthy liver microsomal stability (human, T1/2 = 340.4 min), good pharmacokinetic parameters (rat, T1/2 p.o. = 2.11 h, AUClast p.o. = 10 900 h ng mL-1) and high oral bioavailability (rat, F = 97.9%), while also being inactive towards hERG (IC50 > 10 µM).
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The global increase of cutaneous wounds imposes huge health and financial burdens on patients and society. Despite improved wound healing outcomes, conventional wound dressings are far from ideal, owing to the complex healing process. Smart wound dressings, which are sensitive to or interact with changes in wound condition or environment, have been proposed as appealing therapeutic platforms to effectively facilitate wound healing. In this review, the wound healing processes and features of existing biomaterials are firstly introduced, followed by summarizing the mechanisms of smart responsive materials. Afterwards, recent advances and designs in smart and versatile materials of extensive applications for cutaneous wound healing were submarined. Finally, clinical progresses, challenges and future perspectives of the smart wound dressing are discussed. Overall, by mapping the composition and intrinsic structure of smart responsive materials to their individual needs of cutaneous wounds, with particular attention to the responsive mechanisms, this review is promising to advance further progress in designing smart responsive materials for wounds and drive clinical translation.
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BACKGROUND: Impaired wound re-epithelialization contributes to cutaneous barrier reconstruction dysfunction. Recently, N6-methyladenosine (m6A) RNA modification has been shown to participate in the determination of RNA fate, and its aberration triggers the pathogenesis of numerous diseases. Howbeit, the function of m6A in wound re-epithelialization remains enigmatic. METHODS: Alkbh5â/â mouse was constructed to study the rate of wound re-epithelialization after ALKBH5 ablation. Integrated high-throughput analysis combining methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq was used to identify the downstream target of ALKBH5. In vitro and in vivo rescue experiments were conducted to verify the role of the downstream target on the functional phenotype of ALKBH5-deficient cells or animals. Furthermore, the interacting reader protein and regulatory mechanisms were determined through RIP-qPCR, RNA pull-down, and RNA stability assays. RESULTS: ALKBH5 was specifically upregulated in the wound edge epidermis. Ablation of ALKBH5 suppressed keratinocyte migration and resulted in delayed wound re-epithelialization in Alkbh5â/â mouse. Integrated high-throughput analysis revealed that PELI2, an E3 ubiquitin protein ligase, serves as the downstream target of ALKBH5. Concordantly, exogenous PELI2 supplementation partially rescued keratinocyte migration and accelerated re-epithelialization in ALKBH5-deficient cells, both in vitro and in vivo. In terms of its mechanism, ALKBH5 promoted PELI2 expression by removing the m6A modification from PELI2 mRNA and enhancing its stability in a YTHDF2-dependent manner. CONCLUSIONS: This study identifies ALKBH5 as an endogenous accelerator of wound re-epithelialization, thereby benefiting the development of a reprogrammed m6A targeted therapy for refractory wounds.
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BACKGROUND: Cutaneous squamous cell carcinoma (cSCC) is a highly invasive disease with the potential to metastasize and cause fatality. Therefore, it is crucial to understand the mechanism behind cSCC in order to devise effective strategies to combat this disease. OBJECTIVE: We investigated the function of circ_TNFRSF21/miR-214-3p/CHI3L1 axis in cSCC. METHODS: The features of circ_TNFRSF21 was characterized using Sanger sequencing, and RNase R/actinomycin D treatment. Genes and M1/M2 markers levels were assessed by qRT-PCR and IHC. The proliferation, migration, and invasion of cells were evaluated by CCK-8, colony formation, EdU incorporation, and transwell assays. Tumor growth and metastasis in vivo were evaluated by nude mouse xenograft model. Interactions of circ_TNFRSF21/miR-214-3p and miR-214-3p/CHI3L1 were validated by RNA immunoprecipitation and dual luciferase assay. RESULTS: Circ_TNFRSF21 and CHI3L1 expression were elevated in both human cSCC tissues and cells, whereas miR-214-3p was reduced. Circ_TNFRSF21 silencing or miR-214-3p overexpression suppressed cSCC cell proliferation, migration, invasion, and M2 macrophage polarization. Circ_TNFRSF21 functioned as a sponge for miR-214-3p while miR-214-3p directly targeted CHI3L1. Knockdown of miR-214-3p reversed the effects of circ_TNFRSF21 knockdown on cSCC development, while CHI3L1 upregulation reversed the effects of miR-214-3p overexpression. Furthermore, knockdown of circ_TNFRSF21 inhibited cSCC tumor growth and metastasis in vivo. CONCLUSION: Circ_TNFRSF21 plays a significant role in cSCC progression by enhancing cell proliferation, migration, invasion, and M2 macrophage polarization through inhibiting miR-214-3p and subsequent disinhibition of CHI3L1. These findings deepen our understanding of the molecular mechanism of cSCC and propose the circ_TNFRSF21/miR-214-3p/CHI3L1 axis as promising diagnosis markers or therapeutic targets for cSCC.
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Carcinoma de Células Escamosas , MicroRNAs , Neoplasias Cutâneas , Animais , Camundongos , Humanos , Neoplasias Cutâneas/genética , Proliferação de Células/genética , Macrófagos , MicroRNAs/genética , Linhagem Celular Tumoral , Proteína 1 Semelhante à Quitinase-3 , Receptores do Fator de Necrose TumoralRESUMO
Continuing problems with fewer training opportunities and a greater awareness of patient safety have led to a constant search for an alternative technique to bridge the existing theory-practice gap in plastic surgery training and education. The current COVID-19 epidemic has aggravated the situation, making it urgent to implement breakthrough technological initiatives currently underway to improve surgical education. The cutting edge of technological development, augmented reality (AR), has already been applied in numerous facets of plastic surgery training, and it is capable of realizing the aims of education and training in this field. In this article, we will take a look at some of the most important ways that AR is now being used in plastic surgery education and training, as well as offer an exciting glimpse into the potential future of this field thanks to technological advancements.
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Realidade Aumentada , COVID-19 , Procedimentos de Cirurgia Plástica , Cirurgia Plástica , Realidade Virtual , Humanos , COVID-19/epidemiologiaRESUMO
Chronic non-healing wounds, a prevalent complication of diabetes, are associated with increased mortality in diabetic patients. Excessive accumulation of M1 macrophages in diabetic wounds promotes inflammation and results in dysregulated tissue repair. Adipose tissue macrophages (ATMs) derived from healthy lean donors have the ability to improve glucose tolerance and insulin sensitivity, as well as modulate inflammation. MicroRNAs (miRs), which can be packaged into exosomes (Exos) and secreted from cells, serve as essential regulators of macrophage polarization. Here, we revealed that ATMs isolated from lean mice secrete miRs-containing Exos, which modulate macrophage polarization and promote rapid diabetic wound healing when administered to diabetes-prone db/db mice. The miRs sequence of tissue samples from wounds treated with Exos secreted by lean ATMs (ExosLean) revealed that miR-222-3p was up-regulated. Further analyses showed that inhibiting miR-222-3p using a miR inhibitor impaired the macrophage-reprogramming effect of ExosLean. In the excisional skin wound mouse model, locally inhibiting miR-222-3p disrupted healing dynamics and failed to modulate macrophage polarization. Mechanistic studies revealed a connection between miR-222-3p, Bcl2l11/Bim, an inflammatory response effector, macrophage polarization, and diabetic wound healing. In summary, ExosLean act as positive regulators of macrophage polarization by regulating miR levels in wounds and accelerating wound healing, and thus have important implications for wound management in diabetes.
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Diabetes Mellitus , Exossomos , MicroRNAs , Camundongos , Animais , Tecido Adiposo , MicroRNAs/genética , MicroRNAs/farmacologia , Inflamação , Macrófagos , CicatrizaçãoRESUMO
Commonly overexpressed in many cancers and associated with tumor growth, metastasis, drug resistance, and poor overall survival, Axl has emerged as a promising target for cancer therapy. However, the availability of new chemical forms for Axl inhibition is limited. Herein, we present the development and characterization of novel Axl inhibitors, including the design, synthesis, and structure-activity relationships (SARs) of a series of diphenylpyrimidine-diamine derivatives. Most of these compounds exhibited remarkable activity against the Axl kinase. In particular, the promising compound m16 showed the highest enzymatic inhibitory potency (IC50 = 5 nM) and blocked multiple tumor cells' proliferation potencies (the CC50 of 4 out of 42 cancer cell lines <100 nM). Furthermore, compound m16 also possessed preferable pharmacokinetic profiles and liver microsome stability. All these favorable results make m16 a good leading therapeutic candidate for further development.
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In recent years, the role of circular RNA in cancer cells has been studied broadly; however, the functional significance of circular RNA in the regulation of the tumor microenvironment (TME) is not fully understood. In this study, we aimed to reveal the role of circ_TNFRSF21 in M2 macrophage-induced cutaneous squamous cell carcinoma (cSCC) angiogenesis. Quantitative polymerase chain reaction and Western blotting were performed to determine the levels of the indicated genes. Direct binding between circ_TNFRSF21 and miR-3619-5p, miR-3619-5p, and ROCK2 was verified by dual-luciferase activity. The migration and invasion of human umbilical vein endothelial cells were evaluated by wound healing and transwell assays. Tube formation was performed to detect in vitro angiogenesis. Circ_TNFRSF21 and ROCK2 were upregulated in cSCC tissue, while miR-3619-5p was downregulated. Circ_TNFRSF21 negatively regulated the expression of miR-3619-5p, while miR-3619-5p negatively regulated the expression of ROCK2. miR-3619-5p suppressed tube formation by inhibiting ROCK signaling. M2 macrophages facilitated tube formation via the circ_TNFRSF21/miR-3619-5p/ROCK2 axis. Our present study revealed that circ_TNFRSF21 was elevated in M2 macrophages and mediated M2 macrophage-induced tube formation in vitro.
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Carcinoma de Células Escamosas , Macrófagos , MicroRNAs , Neoplasias Cutâneas , Carcinoma de Células Escamosas/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Macrófagos/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismo , Neovascularização Patológica/genética , RNA Circular/genética , Receptores do Fator de Necrose Tumoral , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/patologia , Microambiente Tumoral/genética , Quinases Associadas a rhoRESUMO
Aged skin wounds heal poorly, resulting in medical, economic, and social burdens posed by nonhealing wounds. Age-related defects in repair are associated with reduced myofibroblasts and dysfunctional extracellular matrix (ECM) deposition. Bidirectional cell-cell communication involving exosome-borne cargo such as micro RNAs (miRs) has emerged as a critical mechanism for wound healing and aged tissue regeneration. Here we report that at the wound edge, aged fibroblasts display reduced migration and differentiation into myofibroblasts, with impaired ECM deposition, when compared with young tissue. Proper activation of fibroblasts to myofibroblasts may alleviate age-related defects in wound healing. Herein, an exosome-guided cell technique was performed to induce effective wound healing. Supplementing wounds with exosomes isolated from young mouse wound-edge fibroblasts (exosomesYoung) significantly improved the abundance of myofibroblasts and wound healing in aged mice and caused fibroblasts to migrate and transition to myofibroblasts in vitro. To determine the underlying mechanism, we found that exosomal transfer of miR-125b to fibroblasts inhibited sirtuin 7 (Sirt7), thus accelerating myofibroblast differentiation and wound healing in aged mice. Notably, after epidermal inhibition of miR-125b or overexpression of Sirt7 in fibroblasts, migration and myofibroblast transition were perturbed. Our findings thus reveal that miR-125b is transferred through exosomes from young fibroblasts to old fibroblasts contributes to promoting fibroblast migration and transition to counteract aging, suggesting a potential avenue for anti-aging interventions in wound healing.
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Exossomos , MicroRNAs , Animais , Diferenciação Celular , Fibroblastos , Camundongos , MicroRNAs/genética , CicatrizaçãoRESUMO
Chronic wounds (e.g. diabetic wounds, pressure wounds, vascular ulcers, etc.) do not usually heal in a timely and orderly manner but rather last for years and may lead to irreversible adverse events, resulting in a substantial financial burden for patients and society. Recently, a large amount of evidence has proven that cellular senescence has a crucial influence on chronic nonhealing wounds. As a defensive mechanism, cell senescence is a manner of cell-cycle arrest with increased secretory phenotype to resist death, preventing cells from stress-induced damage in cancer and noncancer diseases. A growing amount of research has advanced the perception of cell senescence in various chronic wounds and focuses on pathological and physiological processes and therapies targeting senescent cells. However, previous reviews have failed to sum up novel understandings of senescence in chronic wounds and emerging strategies targeting senescence. Herein, we discuss the characteristics and mechanisms of cellular senescence and the link between senescence and chronic wounds as well as some novel antisenescence strategies targeting other diseases that may be applied for chronic wounds.
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Although employed to release growth factors (GFs) for regenerative medicine, platelet-rich plasma (PRP) has been hindered by issues like burst effect. Based on collagen sponge scaffolds (CSSs) modified with polydopamine (pDA), a novel dermal regeneration template (DRT) was designed. However, whether it could efficiently deliver PRP and even foster wound healing remained unclear. In this work, after PRP was prepared and pDA-modified CSSs (pDA-CSSs) were fabricated, microscopic observation, GFs release assay and in-vitro biological evaluations of pDA-CSSs with PRP (pDA-CSS@PRP) were performed, followed by BALA-C/nu mice full-thickness skin defects implanted with pDA-CSS@PRP covered by grafted skins (termed as a One-step strategy). As a result, scanning electron microscope demonstrated more immobilized platelets on pDA-CSS' surface with GFs' controlled release via enzyme-linked immunosorbent assay, compared with CSSs. In line with enhanced in-vitro proliferation, adhesion and migration of keratinocytes & endothelial cells, pDA-CSS@PRP were histologically revealed to accelerate wound healing with less scar via rapid angiogenesis, arrangement of more mature collagen, guiding cells to spread, etc. In conclusion, pDA-CSSs have potential to serve as a novel DRT capable of delivering PRP, which may foster full-thickness skin defect healing by means of a One-step strategy.
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BACKGROUND: The shock stage of severe burns is a critical determinant of prognosis and the induction of systemic inflammatory response syndrome and multiple organ failure. Extracellular vesicles (EVs) containing abundant miRNAs are known to participate in various biological processes. Due to the lack of research on alternations of miRNAs in severe burns, our study analyzed the miRNA profiles of EVs in severe burns during the shock stage. METHODS: EVs were extracted from the serum of rats with severe burns (30% of total body surface area, III°), and the expression of miRNAs in serum EVs was determined by next-generation sequencing. Functional analysis of target genes of miRNAs that were significantly differentially expressed (DE) was performed using GO Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG). RESULTS: Thirty-four DE miRNAs were identified at the early stage of severe burn shock and 63 at the late stage of severe burn shock. In addition, miRNA-339-5p, miRNA-1, miRNA-382-5p, miRNA134-5p, miRNA-133a-5p, and miRNA-365a-5p were DE throughout the entire shock stage, based on P < 0.01 and |log2 (foldchange)| ≥ 1 criteria. GO and KEGG analysis revealed that the target genes of DE miRNAs mainly enriched the metabolic process, immune system processes, and signal pathways. CONCLUSION: To our best knowledge, this is the first study demonstrating the miRNA expression profiles of EVs isolated from serum with severe burns during the shock stage. There are significant differences between downregulation and upregulation. Thus, miRNAs have the potential for novel biomarkers for the complication of severe burns.
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Queimaduras/sangue , MicroRNA Circulante/sangue , Vesículas Extracelulares/metabolismo , Regulação da Expressão Gênica , Choque/sangue , Animais , Masculino , Ratos , Ratos Sprague-DawleyRESUMO
BACKGROUND: Three-dimensional (3D) cultivation with biomaterials was proposed to facilitate stem cell epithelial differentiation for wound healing. However, whether human adipose-derived stem cells (hASCs) on collagen sponge scaffold (CSS) better differentiate to keratinocytes remains unclear. METHODS: 3D cultivation with CSS on hASC epidermal differentiation co-cultured with HaCaT cells at air-liquid interface (ALI) was compared with two-dimensional (2D) form and cultivation without "co-culture" or "ALI." Cellular morphology, cell adhesion, and growth condition were evaluated, followed by the protein and gene expression of keratin 14 (K14, keratinocyte specific marker). RESULTS: Typical cobblestone morphology of keratinocytes was remarkably observed in co-cultured hASCs at ALI, but those seeded on the CSS exhibited more keratinocyte-like cells under an invert microscope and scanning electron microscope. Desired cell adhesion and proliferation were confirmed in 3D differentiation groups by rhodamine-labeled phalloidin staining, consistent with H&E staining. Compared with those cultured in 2D culture system or without "ALI," immunofluorescence staining and gene expression analysis revealed hASCs co-cultured over CSS expressed K14 at higher levels at day 15. CONCLUSIONS: CSS is positive to promote epithelial differentiation of hASCs, which will foster a deeper understanding of artificial dermis in skin wound healing and regeneration.
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Tecido Adiposo , Células-Tronco , Diferenciação Celular , Células Cultivadas , Técnicas de Cocultura , Colágeno , Humanos , Alicerces TeciduaisRESUMO
Many dietary flavonoids existing as glycosides in fruits and vegetables are considered bioactive food components with various potential health benefits. Type 2 diabetes mellitus (T2DM) is a complex and polygenic disease with increasing global prevalence and economic burden. In this study, the hypoglycemic effect of avicularin (quercetin-3-O-α-arabinofuranoside), a flavonoid glycoside commonly found in natural plants and fruits, was determined in a high fat diet/streptozotocin induced type 2 diabetes mouse model. Our results demonstrated that dietary avicularin treatment reduced levels of fasting blood glucose, serum TG and LDL-C, liver AST and ALT, and increased hepatic glycogen in T2DM mice. Furthermore, we used RNA-Seq and iTRAQ to compare the gene and protein expression in the livers of the normal control mice (NC), diabetic control mice (DC) and avicularin treated mice (DA100). The differentially expressed genes (DEGs) and differentially expressed proteins (DEPs) were analyzed based on gene annotations and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Integrated analysis of the RNA-Seq and iTRAQ data indicated that the fifteen DEGs/DEPs showed the same trend in mRNA and protein expression levels in comparisons of both NC vs DC and DC vs DA100. KEGG analysis revealed that four DEGs/DEPs (PKM, PEPCK, PYG, and PLA2) in the glycolysis, gluconeogenesis, and arachidonic acid pathway, and six DEPs (Ndufb4, Ndufa6, Cox5a, Cox5b, Cox6c, and ATPSß) in the oxidative phosphorylation signaling pathway, play important roles in avicularin's hypoglycemic effect. We also found six other DEGs/DEPs related to T2DM (CA1, Serpinb6a, AK, Pcolce, Cand2, and Atp2a3), and five related to cancer (Phgdh, Tes, Papss1, Psat1, and Fam49b). We did further verify by qRT-PCR and explored the possible binding modes of avicularin with targeted proteins with molecular docking simulations. Taken together, our results demonstrated the protective effects of avicularin against diabetes and provided a global view about the system-level hypoglycemic mechanisms of avicularin by the comprehensive analysis of transcriptomic and proteomic data in T2DM mice.
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Diabetes Mellitus Experimental/metabolismo , Flavonoides/farmacologia , Fígado/metabolismo , Proteoma/metabolismo , Transcriptoma/genética , Animais , Diabetes Mellitus Experimental/genética , Flavonoides/genética , Flavonoides/metabolismo , Masculino , Camundongos , Proteoma/efeitos dos fármacos , Transcriptoma/efeitos dos fármacosRESUMO
INTRODUCTION: Antihypertension, intensive glucose control (IGC), and lipid lowering were the main therapeutic strategies in diabetes mellitus. However, the comparative effects of them on renoprotection remain unclear. MATERIALS AND METHODS: We searched the PubMed, EMBase, and Cochrane Library up to May 18, 2017, for studies with comparative interventions on regression, end-stage renal disease and all-cause death in diabetes mellitus. Statistical analysis was done using the Bayesian network meta-analysis (NMA). The surface under the cumulative ranking area and median rank were calculated to rank the interventions. RESULTS: A total of 73 randomized controlled trials with 13 3703 participants were included for the comparisons of 14 interventions. Angiotensin-converting enzyme inhibitor plus angiotensin receptor blocker (ACEI-ARB) ranked first in regression (odds ratio, 62; 95% confidence interval, 5.2 to > 999); ACEI-ARB also ranked first in end-stage renal disease decline (odds ratio, 0.58, 95% confidence interval, 0.39 - 0.85), followed by IGC hemoglobin A1c less than 6.5% (odds ratio, 0.58, 95% confidence interval, 0.36 - 0.90). The ACEI plus calcium channel blocker reduced all-cause death leaving other interventions insignificant (odds ratio, < 0.001; 95% confidence interval, < 0.001 to 0.30). ). The surface under the cumulative ranking area analyses also matched the result ranks. CONCLUSIONS: Compared with antihypertension interventions, IGC including IGC hemoglobin A1c less than 6.5% and lipid lowering, ACEI-ARB showed the best renoprotective effects.
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Antagonistas de Receptores de Angiotensina/farmacologia , Inibidores da Enzima Conversora de Angiotensina/farmacologia , Complicações do Diabetes , Hipertensão/tratamento farmacológico , Falência Renal Crônica/tratamento farmacológico , Bloqueadores dos Canais de Cálcio/farmacologia , Causas de Morte , Hemoglobinas Glicadas/metabolismo , Humanos , Mortalidade , Metanálise em Rede , Ensaios Clínicos Controlados Aleatórios como AssuntoRESUMO
Regenerative medicine is a burgeoning field that is important to combat challenging diseases and functional impairments. Compared with traditional cell therapies with evident shortcomings (e.g., cell suspension injection or tissue engineering with scaffolds), scaffold-free cell sheet technology enables transplanted cells to be grafted and fully maintain their viability on target sites. Clinical and experimental studies have advanced the application of cell sheet technology to numerous tissues and organs (e.g., liver, cornea and bone). However, previous reviews have failed to discuss vital aspects of this rapidly developing technology, and many new challenges are gradually emerging. This review aims to provide a comprehensive introduction to cell sheet technology from cell selection to the ultimate applications of cell sheets, and challenges and future visions are also described.
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Medicina Regenerativa/métodos , Transplante de Células-Tronco/métodos , Engenharia Tecidual/métodos , Osso e Ossos/cirurgia , Procedimentos Cirúrgicos Cardíacos , Técnicas de Cultura de Células/métodos , Procedimentos Cirúrgicos Dermatológicos , Humanos , Células-Tronco Pluripotentes Induzidas , Fígado/cirurgia , Células-Tronco MesenquimaisRESUMO
We designed and synthesized N-phenyl γ-lactam derivatives possessing two covalently identical ortho-F nuclei on the N-phenyl group. The F nuclei sited in different chemical environments where they were spatially adjacent to amide and alkyl groups due to hindered rotation around the central N-Ar bond. 19F NMR spectroscopic and X-ray crystallographic methods were used to distinguish the axially prochiral F nuclei and provide structural insights for through-space interactions between F and amide/CH2 groups. Direct spectroscopic evidence for multipolar interactions in F···amide and F···CH2 pairs were provided.
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OBJECTIVE: To evaluate the effects of bisoprolol combined with trimetazidine on the treatment of heart failure patients having concomitant chronic obstructive pulmonary disease (COPD); in comparison with control group treated with standard therapy only. METHODS: A total of 120 heart failure patients having concomitant COPD were selected and randomly divided into a control group and a treatment group according to different treatment methods (n=60). The control group was given continuous low flow oxygen inhalation and inotropic agents, and their cardiac stress was also reduced. The treatment group was treated with bisoprolol fumarate and trimetazidine in addition to treatment for COPD. For all patients, blood gas analysis and parameters reflecting cardiac function were measured respectively before and after treatment. The respiratory symptoms (cough, sputum, polypnea, gasp, dyspnea), limitation of motion (daily life, household duties, entertainment, sports), disease impacts (social contact, emotion, anxiety) and St. George's Respiratory Questionnaire (SGRQ) total scores were observed using SGRQ. RESULTS: The oxygen partial pressure (PaO2) and partial pressure of carbon dioxide (PaCO2) of the treatment group after treatment were significantly different from those before treatment. After treatment, peak E, E/A and IVEF were increased by 41%, 44% and 16% respectively, but peak A, LVPWT/mm and IVST/mm were significantly reduced. The differences in the respiratory symptoms, limitation of motion, disease impacts and SGRQ total scores were statistically significant compared with those before treatment (P<0.05) and those of the control group (P<0.05). CONCLUSION: Combining bisoprolol with trimetazidine in the treatment of heart failure complicating COPD can effectively improve blood gas indices, left ventricular systolic and diastolic functions and the quality of life, thereby alleviating clinical symptoms.
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OBJECTIVE: It is universally acknowledged that acute kidney injury (AKI) often comes following cardiac surgery with severe morbidity and mortality. The impact of statins on the incidence of AKI and mortality after cardiac surgery are controversial, therefore, it is urgent to explore the source of heterogeneity via the subgroup analysis. METHODS: We searched PubMed, ISI and Elsevier to May 31st 2016 for studies which investigated the effects of statins relevant to this theme. Statistical analysis was using RevMan5.2 and Stata12.0. The outcomes were the occurrence of AKI and the mortality after cardiac surgery. For the first time, we discussed the source of heterogeneity on the basis of the characters of patients in the following subgroup analysis. RESULTS: A total of 17 studies with 18,684 statins and 24,033 non-statin users were included. The meta-analysis suggested that statins not only reduced the occurrence of AKI [Odds Ratio (OR) 0.72, 95% Confidence Interval (CI) 0.55-0.94)] in the subjects without high risk factors, also decreased the mortality of the patients suffering AKI (OR 0.40, 95% CI 0.22-0.72). CONCLUSION: Patients undergoing cardiac surgery might benefit from statins by reducing the occurrence of AKI and the mortality of the patients suffering AKI.