RESUMO
Osteoarthritis (OA) is an age-related or post-traumatic degenerative whole joint disease characterized by the rupture of articular cartilage homeostasis, the regulatory mechanisms of which remain elusive. This study identifies the essential role of heterogeneous nuclear ribonucleoprotein K (hnRNPK) in maintaining articular cartilage homeostasis. Hnrnpk expression is markedly downregulated in human and mice OA cartilage. The deletion of Hnrnpk effectively accelerates the development of post-traumatic and age-dependent OA in mice. Mechanistically, the KH1 and KH2 domain of Hnrnpk bind and degrade the mRNA of WWC1. Hnrnpk deletion increases WWC1 expression, which in turn leads to the activation of Hippo signaling and ultimately aggravates OA. In particular, intra-articular injection of LPA and adeno-associated virus serotype 5 expressing WWC1 RNA interference ameliorates cartilage degeneration induced by Hnrnpk deletion, and intra-articular injection of adeno-associated virus serotype 5 expressing Hnrnpk protects against OA. Collectively, this study reveals the critical roles of Hnrnpk in inhibiting OA development through WWC1-dependent downregulation of Hippo signaling in chondrocytes and defines a potential target for the prevention and treatment of OA.
Assuntos
Cartilagem Articular , Condrócitos , Ribonucleoproteínas Nucleares Heterogêneas Grupo K , Via de Sinalização Hippo , Osteoartrite , Proteínas Serina-Treonina Quinases , Transdução de Sinais , Animais , Humanos , Masculino , Camundongos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Condrócitos/metabolismo , Dependovirus/genética , Modelos Animais de Doenças , Regulação da Expressão Gênica , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/metabolismo , Ribonucleoproteínas Nucleares Heterogêneas Grupo K/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Osteoartrite/metabolismo , Osteoartrite/genética , Osteoartrite/etiologia , Osteoartrite/patologia , Osteoartrite/terapia , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Serina-Treonina Quinases/genética , RNA Mensageiro/genética , RNA Mensageiro/metabolismoRESUMO
BACKGROUND: Obesity is often associated with impaired immune responses, including enlarged spleen, increased inflammation, and impaired T cell-mediated function, which may lead to increased susceptibility to infections. Bioactive compounds found in various fruits and vegetables (F&V) have been shown to have strong anti-inflammatory effects. However, few prospective studies have examined the effects of F&V on preventing obesity-associated dysregulation of immune and inflammatory responses. OBJECTIVE: To determine the impact of different levels of a mixture of F&V incorporated in a high-fat diet (HFD) on immune function changes in a diet-induced obesity animal model. METHODS: Six-week-old male C57BL/6J mice were randomly assigned to one of five groups (n = 12/group): matched low-fat control (LF, 10% kcal fat) or high-fat diet (HFD, 45% kcal fat) supplemented with 0%, 5%, 10%, or 15% (wt/wt) freeze-dried powder of the most consumed F&V (human equivalent of 0, 3, 5-7, 8-9 servings/d, respectively) for 20 weeks. Spleen weight was recorded, and the immunophenotype of splenocytes was evaluated by flow cytometry. Ex vivo splenic lymphocyte proliferation was assessed by thymidine incorporation and serum cytokines were measured by Meso Scale Discovery. RESULTS: Mice fed the HFD had significantly higher spleen weight, decreased splenic CD8+ lymphocytes, suppressed T lymphocyte proliferation, and reduced serum IL-1ß and IFN-γ levels compared to those fed the LF diet. Feeding mice with the HFD supplemented with 10% or 15% F&V restored HFD-associated changes of these affected biomarkers compared to those fed HFD only. Further, a significant correlation was found between immunological markers and F&V level. CONCLUSIONS: These results suggest that increased consumption of F&V has beneficial effects in preventing HFD-associated dysregulation of immune function.
RESUMO
Due to its unique structure, articular cartilage has limited abilities to undergo self-repair after injury. Additionally, the repair of articular cartilage after injury has always been a difficult problem in the field of sports medicine. Previous studies have shown that the therapeutic use of mesenchymal stem cells (MSCs) and their extracellular vesicles (EVs) has great potential for promoting cartilage repair. Recent studies have demonstrated that most transplanted stem cells undergo apoptosis in vivo, and the apoptotic EVs (ApoEVs) that are subsequently generated play crucial roles in tissue repair. Additionally, MSCs are known to exist under low-oxygen conditions in the physiological environment, and these hypoxic conditions can alter the functional and secretory properties of MSCs as well as their secretomes. This study aimed to investigate whether ApoEVs that are isolated from adipose-derived MSCs cultured under hypoxic conditions (hypoxic apoptotic EVs [H-ApoEVs]) exert greater effects on cartilage repair than those that are isolated from cells cultured under normoxic conditions. Through in vitro cell proliferation and migration experiments, we demonstrated that H-ApoEVs exerted enhanced effects on stem cell proliferation, stem cell migration, and bone marrow derived macrophages (BMDMs) M2 polarization compared to ApoEVs. Furthermore, we utilized a modified gelatine matrix/3D-printed extracellular matrix (ECM) scaffold complex as a carrier to deliver H-ApoEVs into the joint cavity, thus establishing a cartilage regeneration system. The 3D-printed ECM scaffold provided mechanical support and created a microenvironment that was conducive to cartilage regeneration, and the H-ApoEVs further enhanced the regenerative capacity of endogenous stem cells and the immunomodulatory microenvironment of the joint cavity; thus, this approach significantly promoted cartilage repair. In conclusion, this study confirmed that a ApoEVs delivery system based on a modified gelatine matrix/3D-printed ECM scaffold together with hypoxic preconditioning enhances the functionality of stem cell-derived ApoEVs and represents a promising approach for promoting cartilage regeneration.
Assuntos
Cartilagem Articular , Vesículas Extracelulares , Células-Tronco Mesenquimais , Humanos , Hidrogéis , Alicerces Teciduais/química , Gelatina , Células-Tronco , HipóxiaRESUMO
The regulation of fibrotic activities is key to improving pathological remodelling post-myocardial infarction (MI). Currently, in the clinic, safe and curative therapies for cardiac fibrosis and improvement of the pathological fibrotic environment, scar formation and pathological remodelling post-MI are lacking. Previous studies have shown that miR-486 is involved in the regulation of fibrosis. However, it is still unclear how miR-486 functions in post-MI regeneration. Here, we first demonstrated that miR-486 targeting SRSF3/p21 mediates the senescence of cardiac myofibroblasts to improve their fibrotic activity, which benefits the regeneration of MI by limiting scar size and post-MI remodelling. miR-486-targeted silencing has high potential as a novel target to improve fibrotic activity, cardiac fibrosis and pathological remodelling.
Assuntos
MicroRNAs , Infarto do Miocárdio , Cicatriz/patologia , Fibrose , Humanos , MicroRNAs/genética , Infarto do Miocárdio/genética , Infarto do Miocárdio/patologia , Infarto do Miocárdio/terapia , Miocárdio/patologia , Miofibroblastos/patologia , Fatores de Processamento de Serina-Arginina/genéticaRESUMO
Spinal cord injury (SCI) is a common traumatic disease of the nervous system. The pathophysiological process of SCI includes primary injury and secondary injuries. An excessive inflammatory response leads to secondary tissue damage, which in turn exacerbates cellular and organ dysfunction. Due to the irreversibility of primary injury, current research on SCI mainly focuses on secondary injury, and the inflammatory response is considered the primary target. Thus, modulating the inflammatory response has been suggested as a new strategy for the treatment of SCI. In this study, microglial cell lines, primary microglia, and a rat SCI model were used, and we found that WKYMVm/FPR2 plays an anti-inflammatory role and reduces tissue damage after SCI by suppressing the extracellular signal-regulated kinases 1 and 2 (ERK1/2) and nuclear factor-κB (NF-κB) signaling pathways. FPR2 was activated by WKYMVm, suppressing the secretion of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1ß (IL-1ß) by inhibiting M1 microglial polarization. Moreover, FPR2 activation by WKYMVm could reduce structural disorders and neuronal loss in SCI rats. Overall, this study illustrated that the activation of FPR2 by WKYMVm repressed M1 microglial polarization by suppressing the ERK1/2 and NF-κB signaling pathways to alleviate tissue damage and locomotor decline after SCI. These findings provide further insight into SCI and help identify novel treatment strategies.
Assuntos
Microglia , Traumatismos da Medula Espinal , Animais , Inflamação/metabolismo , Microglia/metabolismo , NF-kappa B/metabolismo , Ratos , Receptores de Lipoxinas/agonistas , Receptores de Lipoxinas/metabolismo , Transdução de Sinais , Traumatismos da Medula Espinal/metabolismoRESUMO
BACKGROUND: Epidemiologic studies suggest that fruit and vegetable (F&V) consumption is inversely associated with incidence of cardiovascular disease (CVD). However, evidence for causality is lacking, and the underlying mechanisms are not well understood. OBJECTIVES: We aimed to determine whether there is a causal relation between consuming high levels of F&V and prevention of atherosclerosis, the hallmark of CVD pathogenesis. Furthermore, the underlying mechanisms were determined. METHODS: Six-week-old male LDL receptor-knockout mice were randomly assigned to 3 diet groups (12 mice/group) for 20 wk: control (CON, 10% kcal fat, 0.20 g/kg cholesterol), atherogenic (Ath, 27% kcal fat, 0.55 g/kg cholesterol), and Ath supplemented with 15% F&V (Ath + FV) (equivalent to 8-9 servings/d in humans). F&V was added as a freeze-dried powder that was prepared from the 24 most commonly consumed F&Vs in the United States. Body weight, aortic atherosclerotic lesion area, hepatic steatosis area, serum lipid profile and proinflammatory cytokine TNF-α concentrations, gut microbiota, and liver TNF-α and fatty acid synthase (Fasn) mRNA concentrations were assessed. RESULTS: F&V supplementation did not affect weight gain. Mice fed the Ath + FV diet had a smaller aortic atherosclerotic lesion area (71.7% less) and hepatic steatosis area (80.7% less) than those fed the Ath diet (both P < 0.001) independent of impact on weight, whereas no difference was found between Ath + FV and CON groups in these 2 pathologic markers. Furthermore, F&V supplementation prevented Ath diet-induced dyslipidemia (high concentrations of serum TG and VLDL cholesterol and lower concentrations of HDL cholesterol), reduced serum TNF-α concentration (by 21.5%), suppressed mRNA expression of liver TNF-α and Fasn, and ameliorated Ath-induced gut microbiota dysbiosis. CONCLUSIONS: Our results indicate that consuming a large quantity and variety of F&Vs causally attenuates diet-induced atherosclerosis and hepatic steatosis in mice. These effects of F&Vs are associated with, and may be mediated through, improved atherogenic dyslipidemia, alleviated gut dysbiosis, and suppressed inflammation.
Assuntos
Aterosclerose/dietoterapia , Aterosclerose/prevenção & controle , Frutas , Receptores de LDL/deficiência , Verduras , Animais , Aterosclerose/etiologia , Dieta Aterogênica/efeitos adversos , Suplementos Nutricionais , Microbioma Gastrointestinal , Teste de Tolerância a Glucose , Fatores de Risco de Doenças Cardíacas , Lipídeos/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Receptores de LDL/genética , Fator de Necrose Tumoral alfa/sangue , Aumento de PesoRESUMO
Due to the sustainable use of wastes, cathode materials of spent lithium-ion batteries are recovered and used as transition metal precursors to prepare metal oxides catalysts for the oxidation of VOCs. In this work, a series of manganese-based and cobalt-based metal oxides are synthesized via different preparation methods. Catalytic activities of the catalysts prepared are investigated through complete oxidation of oxygenated VOCs and the physicochemical properties of optimum samples are characterized. Evaluation results indicate that MnOx (SY) (HT) sample prepared via hydrothermal method and CoOx (GS) (CP) synthesized via co-precipitation method had better performance, because they have higher specific surface area, higher concentration of active oxygen species and high-valence metal ion, as well as better low-temperature reducibility compared to the other multi-metal oxides used in the study. In addition, TD/GC-MS results imply that further oxidation of by-products requires high reaction temperature during VOCs oxidation.
Assuntos
Fontes de Energia Elétrica , Lítio , Eletrodos , Metais , Óxidos , ReciclagemRESUMO
BACKGROUND: Epidemiological studies suggest that higher fruits and vegetables (F&V) consumption correlates with reduced risk of hepatic steatosis, yet evidence for causality and the underlying mechanisms is lacking. OBJECTIVES: We aimed to determine the causal relation between F&V consumption and improved metabolic disorders in mice fed high-fat (HF) (Experiment-1) or normal-fat (Experiment-2) diets and its underlying mechanisms. METHODS: Six-week-old male C57BL/6J mice were randomly grouped and fed diets supplemented at 0%-15% (wt:wt) with a freeze-dried powder composed of 24 commonly consumed F&V (human equivalent of 0-9 servings/d) for 20 wk. In Experiment-1, mice were fed an HF (45% kcal fat) diet with 0% (HF0), 5%, 10%, or 15% (HF15) F&V or a matched low-fat control diet (10% kcal fat). In Experiment-2, mice were fed an AIN-93 diet (basal) (B, 16% kcal fat) with 0% (B0), 5%, 10%, or 15% (B15) F&V supplementation. Body weight and composition, food intake, hepatic steatosis, inflammation, ceramide levels, sphingomyelinase activity, and gut microbiota were assessed. RESULTS: In Experiment-1, mice fed the HF15 diet had lower weight gain (17.9%), hepatic steatosis (48.4%), adipose tissue inflammation, blood (24.6%) and liver (33.9%) ceramide concentrations, and sphingomyelinase activity (38.8%) than HF0 mice (P < 0.05 for all). In Experiment-2, mice fed the B15 diet had no significant changes in weight gain but showed less hepatic steatosis (28.5%), blood and adipose tissue inflammation, and lower blood (30.0%) ceramide concentrations than B0 mice (P < 0.05 for all). These F&V effects were associated with favorable microbiota changes. CONCLUSIONS: These findings represent the first evidence for a causal role of high F&V intake in mitigating hepatic steatosis in mice. These beneficial effects may be mediated through changes in ceramide and/or gut microbiota, and suggest that higher than currently recommended servings of F&V may be needed to achieve maximum health benefits.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Fígado Gorduroso/prevenção & controle , Frutas , Doenças Metabólicas/etiologia , Verduras , Ração Animal , Animais , Ceramidas/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Distribuição Aleatória , Fator de Necrose Tumoral alfa/genética , Fator de Necrose Tumoral alfa/metabolismo , Aumento de PesoRESUMO
Circadian rhythm exerts its influence on animal physiology and behavior by regulating gene expression at various levels. Here we systematically explored circadian long non-coding RNAs (lncRNAs) in mouse liver and examined their circadian regulation. We found that a significant proportion of circadian lncRNAs are expressed at enhancer regions, mostly bound by two key circadian transcription factors, BMAL1 and REV-ERBα. These circadian lncRNAs showed similar circadian phases with their nearby genes. The extent of their nuclear localization is higher than protein coding genes but less than enhancer RNAs. The association between enhancer and circadian lncRNAs is also observed in tissues other than liver. Comparative analysis between mouse and rat circadian liver transcriptomes showed that circadian transcription at lncRNA loci tends to be conserved despite of low sequence conservation of lncRNAs. One such circadian lncRNA termed lnc-Crot led us to identify a super-enhancer region interacting with a cluster of genes involved in circadian regulation of metabolism through long-range interactions. Further experiments showed that lnc-Crot locus has enhancer function independent of lnc-Crot's transcription. Our results suggest that the enhancer-associated circadian lncRNAs mark the genomic loci modulating long-range circadian gene regulation and shed new lights on the evolutionary origin of lncRNAs.
Assuntos
Fatores de Transcrição ARNTL/genética , Ritmo Circadiano/genética , Elementos Facilitadores Genéticos , Regulação da Expressão Gênica , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , RNA Longo não Codificante/genética , Transcriptoma , Fatores de Transcrição ARNTL/metabolismo , Animais , Sítios de Ligação , Núcleo Celular/metabolismo , Perfilação da Expressão Gênica , Loci Gênicos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Ligação Proteica , RNA Longo não Codificante/metabolismo , RatosRESUMO
Mammalian circadian rhythm is established by the negative feedback loops consisting of a set of clock genes, which lead to the circadian expression of thousands of downstream genes in vivo. As genome-wide transcription is organized under the high-order chromosome structure, it is largely uncharted how circadian gene expression is influenced by chromosome architecture. We focus on the function of chromatin structure proteins cohesin as well as CTCF (CCCTC-binding factor) in circadian rhythm. Using circular chromosome conformation capture sequencing, we systematically examined the interacting loci of a Bmal1-bound super-enhancer upstream of a clock gene Nr1d1 in mouse liver. These interactions are largely stable in the circadian cycle and cohesin binding sites are enriched in the interactome. Global analysis showed that cohesin-CTCF co-binding sites tend to insulate the phases of circadian oscillating genes while cohesin-non-CTCF sites are associated with high circadian rhythmicity of transcription. A model integrating the effects of cohesin and CTCF markedly improved the mechanistic understanding of circadian gene expression. Further experiments in cohesin knockout cells demonstrated that cohesin is required at least in part for driving the circadian gene expression by facilitating the enhancer-promoter looping. This study provided a novel insight into the relationship between circadian transcriptome and the high-order chromosome structure.
Assuntos
Fatores de Transcrição ARNTL/genética , Proteínas de Ciclo Celular/genética , Proteínas Cromossômicas não Histona/genética , Ritmo Circadiano/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Proteínas Repressoras/genética , Fatores de Transcrição ARNTL/metabolismo , Animais , Fator de Ligação a CCCTC , Proteínas de Ciclo Celular/metabolismo , Proteínas Cromossômicas não Histona/metabolismo , Cromossomos/genética , Retroalimentação Fisiológica , Fator de Transcrição de Proteínas de Ligação GA/genética , Fator de Transcrição de Proteínas de Ligação GA/metabolismo , Regulação da Expressão Gênica , Fígado/metabolismo , Camundongos , Camundongos Knockout , Proteínas Nucleares/genética , Proteínas Nucleares/metabolismo , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Regiões Promotoras Genéticas , Ligação Proteica , Proteínas Repressoras/metabolismo , CoesinasRESUMO
The extracellular matrix (ECM) is a dynamic and intricate three-dimensional (3D) microenvironment with excellent biophysical, biomechanical, and biochemical properties that may directly or indirectly regulate cell behavior, including proliferation, adhesion, migration, and differentiation. Compared with tissue-derived ECM, cell-derived ECM potentially has more advantages, including less potential for pathogen transfer, fewer inflammatory or anti-host immune responses, and a closer resemblance to the native ECM microenvironment. Different types of cell-derived ECM, such as adipose stem cells, synovium-derived stem cells and bone marrow stromal cells, their effects on articular chondrocytes which have been researched. In this study, we aimed to develop a 3D cell culture substrate using decellularized ECM derived from human umbilical cord-derived mesenchymal stem cells (hUCMSCs), and evaluated the effects on articular chondrocytes. We evaluated the morphology and components of hUCMSC-derived ECM using physical and chemical methods. Morphological, histological, immunohistochemical, biochemical, and real-time PCR analyses demonstrated that proliferation and differentiation capacity of chondrocytes using the 3D hUCMSC-derived ECM culture substrate was superior to that using non-coated two-dimensional plastic culture plates. In conclusion, 3D decellularized ECM derived from hUCMSCs offers a tissue-specific microenvironment for in vitro culture of chondrocytes, which not only markedly promoted chondrocyte proliferation but also preserved the differentiation capacity of chondrocytes. Therefore, our findings suggest that a 3D cell-derived ECM microenvironment represents a promising prospect for autologous chondrocyte-based cartilage tissue engineering and regeneration. The hUCMSC-derived ECM as a biomaterial is used for the preparation of scaffold or hybrid scaffold products which need to further study in the future.
Assuntos
Diferenciação Celular , Proliferação de Células , Condrócitos/citologia , Matriz Extracelular/metabolismo , Células-Tronco Mesenquimais/citologia , Cordão Umbilical/citologia , Tecido Adiposo/citologia , Animais , Materiais Biocompatíveis/metabolismo , Cartilagem Articular/citologia , Adesão Celular , Técnicas de Cultura de Células , Movimento Celular , Condrócitos/metabolismo , Condrogênese , Fibronectinas/química , Humanos , Inflamação , Coelhos , Engenharia Tecidual/instrumentação , Alicerces TeciduaisRESUMO
Cartilage engineering facilitates repair and regeneration of damaged cartilage using engineered tissue that restores the functional properties of the impaired joint. The seed cells used most frequently in tissue engineering, are chondrocytes and mesenchymal stem cells. Seed cells activity plays a key role in the regeneration of functional cartilage tissue. However, seed cells undergo undesirable changes after in vitro processing procedures, such as degeneration of cartilage cells and induced hypertrophy of mesenchymal stem cells, which hinder cartilage tissue engineering. Compared to monoculture, which does not mimic the in vivo cellular environment, co-culture technology provides a more realistic microenvironment in terms of various physical, chemical, and biological factors. Co-culture technology is used in cartilage tissue engineering to overcome obstacles related to the degeneration of seed cells, and shows promise for cartilage regeneration and repair. In this review, we focus first on existing co-culture systems for cartilage tissue engineering and related fields, and discuss the conditions and mechanisms thereof. This is followed by methods for optimizing seed cell co-culture conditions to generate functional neo-cartilage tissue, which will lead to a new era in cartilage tissue engineering.
Assuntos
Cartilagem Articular/lesões , Terapia Baseada em Transplante de Células e Tecidos/métodos , Condrócitos/transplante , Transplante de Células-Tronco Mesenquimais , Engenharia Tecidual/métodos , Cartilagem Articular/citologia , Comunicação Celular/fisiologia , Condrócitos/citologia , Técnicas de Cocultura , Humanos , Células-Tronco Mesenquimais/citologiaRESUMO
Articular cartilage defects have very limited self-repair potential, and traditional bone marrow-stimulating therapy is not effective. Cartilage tissue engineering using bone marrow mesenchymal stem cells (BMSCs) and adipose tissue-derived mesenchymal stem cells (ADSCs) is considered an attractive treatment for cartilage lesions and osteoarthritis. However, studies proved that both BMSCs and ADSCs have their own advantages and shortcomings, including their sources, isolation methods, characterizations and differentiation potential. Understanding the properties and differences between ADSCs and BMSCs is important for clinical application in cartilage regeneration. This review provides an overview of BMSCs and ADSCs based on their characterization, isolation. Then, we summarized their differentiation potential in different experimental conditions. Finally, we discuss the applications of BMSCs and ADSCs in scaffold-free and scaffold-based cartilage tissue engineering. Based on different properties of BMSCs and ADSCs, and patient's physical condition, a more suitable therapeutic strategy can be selected.
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Tecido Adiposo/citologia , Células da Medula Óssea/citologia , Cartilagem/fisiologia , Células-Tronco Mesenquimais/citologia , Engenharia Tecidual/métodos , Animais , Biomarcadores/metabolismo , Cartilagem/citologia , Diferenciação Celular , Humanos , Células-Tronco Mesenquimais/fisiologiaRESUMO
Meniscus injuries appear to be becoming increasingly common and pose a challenge for orthopedic surgeons. However, there is no curative approach for dealing with defects in the inner meniscus region due to its avascular nature. Numerous strategies have been applied to regenerate and repair meniscus defects and native tissue-based strategies have received much attention. Native tissue usually has good biocompatibility, excellent mechanical properties and a suitable microenvironment for cellular growth, adhesion, redifferentiation, extracellular matrix deposition and remodeling. Classically, native tissue-based strategies for meniscus repair and regeneration are divided into autogenous and heterogeneous tissue transplantation. Autogenous tissue transplantation is performed more widely than heterogeneous tissue transplantation because there is no immunological rejection and the success rates are higher. This review first discusses the native meniscus structure and function and then focuses on the use of the autogenous tissue for meniscus repair and regeneration. Finally, it summarizes the advantages and disadvantages of heterogeneous tissue transplantation. We hope that this review provides some suggestions for the future design of meniscus repair and regeneration strategies.
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Menisco/patologia , Menisco/fisiopatologia , Regeneração , Cicatrização , Animais , Humanos , Menisco/transplante , Alicerces Teciduais/químicaRESUMO
The level of 5-hydroxymethylcytosine (5-hmC) converted by ten-eleven translocation (TET) family is decreased in cancers. However, whether 5-hmC level is perturbed in early stages of carcinogenesis caused by genotoxic carcinogens is not defined. 5-hmC levels and TET2 expression were measured in liver of rats treated with genotoxic carcinogens, riddelliine, or aristolochic acid. Levels of 5-hmC and TET2 expression decreased in the liver of the carcinogens-treated rats. Loss of 5-hmC correlates well with documented induction of genetic mutations by the carcinogens, suggesting that TET2-mediated 5-hydroxymethylation plays an epigenetic role in early state of carcinogenesis.
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Ácidos Aristolóquicos/toxicidade , Carcinógenos/toxicidade , Citosina/análogos & derivados , Fígado/metabolismo , Alcaloides de Pirrolizidina/toxicidade , 5-Metilcitosina/análogos & derivados , Animais , Carcinogênese/efeitos dos fármacos , Citosina/metabolismo , Proteínas de Ligação a DNA/metabolismo , Epigênese Genética/efeitos dos fármacos , Mutação/efeitos dos fármacos , Neoplasias/induzido quimicamente , Neoplasias/metabolismo , Ratos , Ratos Endogâmicos F344 , Ratos TransgênicosRESUMO
Sentinel lymph node biopsies are conducted to stage patients with newly diagnosed melanomas that have histopathological attributes conferring defined levels of metastatic potential. Because benign nevic cells may also form 'deposits' in lymph nodes (nodal nevus), the pathological evaluation for metastatic melanoma within sentinel lymph nodes can be challenging. Twenty-eight sentinel lymph node biopsy cases containing either metastatic melanoma (N=18) or nodal nevi (N=10) were retrieved from the archives of the Brigham and Women's Hospital, Department of Pathology (2011-2014). In addition, two sentinel lymph node cases that were favored to represent metastatic disease but whose histopathological features were viewed as equivocal, with melanoma favored, were also included. Dual labeling for the melanocyte lineage marker, MART-1, and the epigenetic marker, 5-hydroxymethylcytosine, a functionally significant indicator that has been shown to distinguish benign nevi from melanoma, was performed on all cases using immunohistochemistry and/or direct immunofluorescence. All (18 of 18) metastatic melanoma cases showed complete loss of 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells, and all (10 of 10) nodal nevus cases demonstrated 5-hydroxymethylcytosine nuclear staining in MART-1-positive cells. In addition, 5-hydroxymethylcytosine staining confirmed the favored diagnoses of metastatic melanoma in the two 'equivocal' cases. Thus, 5-hydroxymethylcytosine may be a useful adjunctive marker to distinguish between benign nodal nevi and metastatic melanoma during the evaluation of sentinel lymph node biopsies for metastatic melanoma.
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Citosina/análogos & derivados , Linfonodos/patologia , Metástase Linfática/diagnóstico , Melanoma/diagnóstico , Nevo/diagnóstico , Neoplasias Cutâneas/diagnóstico , 5-Metilcitosina/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Biomarcadores Tumorais/análise , Citosina/análise , Citosina/biossíntese , Feminino , Imunofluorescência , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Biópsia de Linfonodo SentinelaRESUMO
INTRODUCTION: Wallerian degeneration (WD) is an important area of research in modern neuroscience. Many protein expressions are regulated by differentially expressed genes in WD, but the precise mechanisms are elusive. METHODS: In this study, we profiled differentially expressed proteins in WD after rat sciatic nerve injury using an antibody array. RESULTS: Functional analysis positively identified cell proliferation, regulation of cell proliferation, and immune system processes. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed molecular networks related mainly to cytokine-cytokine receptor interaction, the mitogen-activated proteinkinase (MAPK) signaling pathway, apoptosis, the toll-like receptor (TLR) signaling pathway, and the Janus kinase (Jak) - signal transducer and activator of transcription (STAT) signaling pathway. Interactions between these differential proteins were well established and regulated by the key factors transforming growth factor beta 1 (TGF-ß1), toll-like receptor 4 (TLR4), Fas ligand (FasL), and 5'-AMP-activated protein kinase catalytic subunit alpha-1 (PRKAA1). CONCLUSIONS: These results provide information related to functional analysis of differentially expressed genes during WD.
Assuntos
Perfilação da Expressão Gênica , Nervo Isquiático/lesões , Degeneração Walleriana/genética , Animais , Biotina , Western Blotting , Análise por Conglomerados , Biologia Computacional , Redes Reguladoras de Genes , Masculino , Degeneração Neural/genética , Regeneração Nervosa/genética , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase em Tempo Real , Transdução de Sinais/fisiologiaRESUMO
To study the temperature sensitivity of the destruction of organic compounds in supercritical water oxidation process (SCWO), oxidation effects of twelve chemicals in supercritical water were investigated. The SCWO reaction rates of different compounds improved to varying degrees with the increase of temperature, so the highest slope of the temperature-effect curve (imax) was defined as the maximum ratio of removal ratio to working temperature. It is an important index to stand for the temperature sensitivity effect in SCWO. It was proven that the higher imax is, the more significant the effect of temperature on the SCWO effect is. Since the high-temperature area of SCWO equipment is subject to considerable damage from fatigue, the temperature is of great significance in SCWO equipment operation. Generally, most compounds (imax > 0.25) can be completely oxidized when the reactor temperature reaches 500°C. However, some compounds (imax > 0.25) need a higher temperature for complete oxidation, up to 560°C. To analyze the correlation coefficients between imax and various molecular descriptors, a quantum chemical method was used in this study. The structures of the twelve organic compounds were optimized by the Density Functional Theory B3LYP/6-311G method, as well as their quantum properties. It was shown that six molecular descriptors were negatively correlated to imax while other three descriptors were positively correlated to imax. Among them, dipole moment had the greatest effect on the oxidation thermodynamics of the twelve organic compounds. Once a correlation between molecular descriptors and imax is established, SCWO can be run at an appropriate temperature according to molecular structure.
Assuntos
Compostos Orgânicos/química , Purificação da Água , Água/química , Oxirredução , TemperaturaRESUMO
Pneumonia is a major public health problem for older adults, being one of the leading causes of hospitalization and death, particularly for elderly nursing home residents. We previously conducted a clinical trial in which we demonstrated that 29% of nursing home residents had low serum zinc levels coinciding with a two-fold increase in pneumonia incidence and duration in comparison to individuals with adequate serum zinc levels. However, causality could not be inferred and necessitates a double-blind clinical trial. To determine the appropriate supplementation dose for such a trial we are conducting a randomized, placebo-controlled, double-blind clinical pilot trial aimed at delineating the optimal dosage (30 and 60 mg/day elemental Zn) and establishing safety. The results from the pilot study will be leveraged to inform our larger randomized clinical trial designed to study the effect of zinc supplementation in nursing home elderly with low serum zinc levels on respiratory infections, antibiotic use, and duration of sick days with pneumonia. In tandem with dose optimization, we will evaluate the correlation between serum zinc and pan-T cell zinc levels, given that T cells and their zinc levels are important in the response and resolution of respiratory infections but whose correlation has only been extrapolated and not demonstrated. Herein we present the study rationale and protocol, as well as discuss specific challenges we encountered in securing a manufacturer for the study agents and when recruiting from nursing home populations during the COVID-19 pandemic. In light of these experiences, we provide recommendations for future clinical trials under circumstances where supply chains are disrupted, and recruitment pools are constrained or unavailable. Clinical trial registration: https://clinicaltrials.gov/, NCT05527899.
RESUMO
Color is one of the most important indicators for the flue-cured tobacco quality. The color change of tobacco has a great relationship with the natural pigments in the tobacco. The relationship between color characteristics and the content of natural pigments in tobacco leaves during curing was investigated. The middle part of variety K326 tobacco was taken at each key time point during the curing process to determine the changes of color characteristics, moisture, pigment and polyphenol content. The results showed that moisture content of wet basis of tobacco gradually decreased from 72 to 18% during the curing process, the b* value increased and then decreased, and the a* value increased significantly. The lutein and ß-carotene content decreased to 63.83 µg/g and 28.3 µg/g, respectively. The total polyphenols content increased to 50.19 mg/g. Meanwhile, the a* value was significantly and positively correlated with polyphenols content and negatively correlated with pigments content. Cluster analysis showed that the samples were divided into three categories: samples with the curing time of 0 h, 24-72 h, and 84-132 h. These results demonstrated that the color change of tobacco during curing process can be divided into three stages from the perspective of chemical composition, which are strongly related to the degradation of pigments and the transformation of polyphenols.