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Background: Long non-coding RNAs are important regulators in cancer biology and function either as tumor suppressors or as oncogenes. Their dysregulation has been closely associated with tumorigenesis. LINC00265 is upregulated in lung adenocarcinoma and is a prognostic biomarker of this cancer. However, the mechanism underlying its function in cancer progression remains poorly understood. Methods: Here, the regulatory role of LINC00265 in lung adenocarcinoma was examined using lung cancer cell lines, clinical samples, and xenografts. Results: We found that high levels of LINC00265 expression were associated with shorter overall survival rate of patients, whereas knockdown of LINC00265 inhibited proliferation of cancer cell lines and tumor growth in xenografts. Western blot and flow cytometry analyses indicated that silencing of LINC00265 induced autophagy and apoptosis. Moreover, we showed that LINC00265 interacted with and stabilized the transcriptional co-repressor Switch-independent 3a (SIN3A), which is a scaffold protein functioning either as a tumor repressor or as an oncogene in a context-dependent manner. Silencing of SIN3A also reduced proliferation of lung cancer cells, which was correlated with the induction of autophagy. These observations raise the possibility that LINC00265 functions to promote the oncogenic activity of SIN3A in lung adenocarcinoma. Conclusions: Our findings thus identify SIN3A as a LINC00265-associated protein and should help to understand the mechanism underlying LINC00265-mediated oncogenesis.
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Apoptose , Autofagia , Proliferação de Células , Neoplasias Pulmonares , RNA Longo não Codificante , Complexo Correpressor Histona Desacetilase e Sin3 , Humanos , RNA Longo não Codificante/genética , Autofagia/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Neoplasias Pulmonares/metabolismo , Apoptose/genética , Animais , Camundongos , Complexo Correpressor Histona Desacetilase e Sin3/genética , Proliferação de Células/genética , Linhagem Celular Tumoral , Proteínas Repressoras/genética , Proteínas Repressoras/metabolismo , Regulação Neoplásica da Expressão Gênica , Estabilidade Proteica , Inativação Gênica , Oncogenes , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/patologia , Adenocarcinoma de Pulmão/metabolismo , Ensaios Antitumorais Modelo de XenoenxertoRESUMO
OBJECTIVE: The best method for femoral fixation in anterior cruciate ligament reconstruction (ACLR) remains controversial. The study assesses the bone tunnel enlargement and clinical outcome in hamstring ACLR using cortical suspension or hybrid (cortical suspension and compression) femoral fixation. METHODS: From January 2010 to December 2021, 102 patients who underwent quadruple hamstring ACLR using cortical suspension (39 patients) or hybrid (63 patients) fixation on the femoral side were retrospectively analyzed. Clinical evaluation was conducted using the international knee documentation committee score, the Lysholm score, the Tegner activity level scale, the knee injury and osteoarthritis outcome score (quality of life score), the Lachman test, and the side-to-side difference by the KT-1000 arthrometer. The complications after the surgery were also evaluated. These data were compared at baseline and last follow-up. The diameters of the femoral tunnel were calculated at three sites: the width of the entrance of the femoral tunnel, 1 cm proximal to the entrance of the femoral tunnel and the largest diameter of the femoral tunnel on magnetic resonance imaging (MRI) coronal images. Bone tunnel widening data were contrasted between MRI images conducted at least 2 years and within 2 weeks after surgery. The morphology of bone tunnel enlargement was also observed and recorded. The categorical parameters were analyzed using the χ2-test and Fisher's exact test. The continuous variables conforming to a normal distribution were analyzed using Student's t-test, and the Mann-Whitney U-test was undertaken between the two groups without normal distribution. RESULTS: Both cortical suspension and hybrid femoral fixation in quadruple hamstring ACLR achieved significantly improved patient-reported outcome scores and knee stability compared to preoperative data. However, no significant differences were found between these two methods in clinical evaluations, postoperative complications, and patient-reported outcome scores. Although the mean diameter of the enlarged bone tunnel was lowered by an additional bioabsorbable interference screw fixation near the joint line, a statistically insignificant difference was found between the hybrid and cortical suspension fixation on the femoral side. There was no statistical difference in the distribution of enlarged bone tunnel morphology between groups. CONCLUSIONS: No significant difference was found in the bone tunnel enlargement and clinical outcome between cortical suspension and hybrid femoral fixation in ACLR using hamstring autograft.
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Lesões do Ligamento Cruzado Anterior , Reconstrução do Ligamento Cruzado Anterior , Tendões dos Músculos Isquiotibiais , Humanos , Ligamento Cruzado Anterior , Estudos Retrospectivos , Qualidade de Vida , Tendões dos Músculos Isquiotibiais/transplante , Articulação do Joelho/cirurgia , Fêmur/cirurgia , Fêmur/patologia , Reconstrução do Ligamento Cruzado Anterior/métodos , Lesões do Ligamento Cruzado Anterior/cirurgia , Lesões do Ligamento Cruzado Anterior/patologia , Tíbia/cirurgiaRESUMO
In a dual-functional lignin valorization system, a harmonious oxidation and reduction rate is a prerequisite for high photocatalytic performance. Herein, an efficient and facile ligand manipulating strategy to balance the redox reaction process is exploited via decorating the surface of the CdS@ZnxCd1-xS@ZnS gradient-alloyed quantum dots with both inorganic ligands of hexafluorophosphate (PF6-) and organic ligands of mercaptopropionic acid (MPA). Inorganic ion ligands in this system provide a promotion for intermediator reduction reactions. By optimizing the ligand composition on the quantum dot surface, we achieve precise control over the extent of oxidation and reduction, enabling selective modification of reaction products; that is, the conversion rate of 2-phenoxy-1-phenylethanol reached 99%. Surface engineering by regulating the ligand type demonstrates that PF6- and thiocyanate (SCN-) inorganic ion ligands contribute significantly toward electron transfer, while MPA ligands have beneficial effects on the hole-transfer procedure, which is predominantly dependent on their steric hindrance, electrostatic action, and passivation effect. The present study offers insights into the development of efficient quantum dot photocatalysts for dual-functional biomass valorization through ligand design.
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Long non-coding RNAs play critical roles in the development of lung cancer by functioning as tumor suppressors or oncogenes. Changes in the expression of LINC01279 have been associated with cell differentiation and human diseases. However, the mechanism underlying LINC01279 activity in tumorigenesis is not clear. Here, we analyzed the function of LINC01279 in lung adenocarcinoma using clinical samples, xenografts, and non-small-cell lung cancer cell lines. We found that LINC01279 is highly expressed in lung adenocarcinoma and may be considered as a predictive factor for this cancer. Knockdown of LINC01279 prevents tumor growth in xenografts and in cancer cell lines by activating autophagy and apoptosis. Molecularly, we revealed that LINC01279 regulates the expression of focal adhesion kinase and extracellular-regulated kinase signaling. In addition, it complexes with and stabilizes the transcriptional co-repressor SIN3A protein. Suppression of focal adhesion kinase and SIN3A also induces apoptosis and prevents tumor progression, suggesting that they may at least in part mediate the oncogenic activity of LINC01279. These results identify LINC01279 as a possible oncogene that plays an important role in the development of lung cancer. Our findings provide insights into the mechanism underlying LINC01279-mediated oncogenesis of lung adenocarcinoma. They may help to discover potential therapeutic targets for cancer diagnosis and prognosis.
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The mitochondrial genome plays a crucial role in the balance of energy and heat production in organisms and, thus, may be under natural selection due to its potential role in adaptive divergence and speciation. Here, we studied natural selection on the mitogenome of Acrossocheilus (Cypriniformes: Cyprinidae), a genus of fish that inhabits a broad latitudinal distribution ranging from the tropics and subtropics through temperate regions. Specifically, we used 25 published mitogenome sequences of Acrossocheilus species to investigate phylogenetic relationships in this genus and detected signals of positive selection on 13 protein-coding, mitochondrial genes. We found that relaxed purifying selection and genetic drift were the predominant evolutionary forces acting on the analyzed mitogenomes. However, we also found evidence of diversifying selection on some codons, indicating episodes of positive selection. Additionally, we analyzed the mitogenomic data within an environmental modeling framework and found that the Ka/Ks ratio of ATP6 may correlated with a mean diurnal temperature range (p = 0.0449), while the Ka/Ks ratio of COX2 may correlated with precipitation during the driest month (p = 0.00761). These results suggest that the mitogenomes of Acrossocheilus species may be involved in evolutionary adaptations to different habitats. Based on this, we believe that our study provides a new insight into the role of the mitochondrial genome of Acrossocheilus species in adaptation to different environments. During our study, we also discovered several cases of paraphyly and polyphyly among accessions of species and their putative synonyms. Thus, our study suggests that a careful reassessment of the taxonomy of Acrossocheilus is using high-quality molecular data merited.
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Cyprinidae , Genoma Mitocondrial , Animais , Códon/genética , Ciclo-Oxigenase 2/genética , Cyprinidae/genética , Evolução Molecular , Genoma Mitocondrial/genética , Filogenia , Seleção GenéticaRESUMO
Consistency evaluation of Traditional Chinese Medicinal preparations (TCMPs) with complex chemical composition is challenging. Chaihuang granules (CHG), as a well-known TCMP, consists of Chaihu (Bupleuri Radix) and Huangqin (Scutellariae Radix) extract. In this work, we used pharmacokinetics and metabolomics to evaluate consistency of CHG products from two different manufacturers. In the pharmacokinetic study, a liquid chromatography tandem mass spectrometry (LC-MS/MS) method was applied to determine the plasma concentration-time profiles of baicalin in rat plasma. Pharmacokinetic parameters, including the maximum concentration in blood (Cmax), area under the curve (AUC), the time to reach Cmax (Tmax), and half-life (T1/2), were calculated to assess the consistency preliminarily. And there was no significant difference in these pharmacokinetic parameters between the two CHG. In LC-MS-based metabolomics, the metabolic response profiles changes based on relative distance values (RDV) to different CHG products were compared. Meanwhile, the kinetic process of 31 differential endogenous metabolites that altered by CHG were determined. Metabolomics data showed the similar metabolic regulation effects to rats of the two formulations. Both pharmacokinetic and metabolomics results indicated there was no significant difference between CHG products. Furthermore, metabolic pathways significantly altered by CHG were elucidated, including phenylalanine, tyrosine and tryptophan biosynthesis, valine, leucine and isoleucine biosynthesis, phenylalanine metabolism, and sphingolipid metabolism. Pharmacokinetics combined with metabolomics could provide a comprehensive perspective for consistency evaluation of CHG.
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Medicamentos de Ervas Chinesas , Espectrometria de Massas em Tandem , Animais , Cromatografia Líquida de Alta Pressão , Cromatografia Líquida , Metabolômica , Ratos , Ratos Sprague-Dawley , Scutellaria baicalensisRESUMO
OBJECTIVE: To compare clinical effects of compound betamethasone and compound betamethasone with hyaluronic acid in treating moderate-severe knee osteoarthritis (KOA). METHODS: A prospective randomized controlled study was conducted in 116 patients with unilateral moderate-severe KOA patients from February 2017 to November 2017 and divided into observation group and control group, 58 patients in each group. In observation group, there were 15 males and 43 females aged from 45 to 80 years old with an average of (66.45±6.31) years old;according to Kellgren-Lawrence(K-L) classification, 42 patients were type â ¢ and 16 patients were type â £;the courses of disease ranged from 4 to 8 years with an average of (5.25±2.21) years;the patients were treated by injecting 1 ml compound betamethasone into knee joint. In control group, there were 13 males and 45 females aged from 45 to 80 years old with an average of (64.89±6.41) years old;according to K-L classification, 43 patients were type â ¢ and 15 patients were type â £;the courses of disease ranged from 4 to 10 years with an average of (5.41±2.35) years;the patients were treated by knee joint injection of 4 ml hyaluronic acid and 1 ml compound betamethasone. Visual analog scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) were used to evaluate clinical effects before treatment and 1 week, 1, month, 3 and 6 months after treatment. RESULTS: Totally 55 patients in observation group were followed up for 6 months, and 3 patients were quit at 3 months after treatment for poor efficacy. Totally 56 patients in control group were followed up for 6 months, and 2 patients were withdrew from the follow-up on the first and third month respectively for poor efficacy. There were no statistical difference in VAS and WOMAC between two groups before treatment and different time points after treatment (P>0.05), and no significant difference in VAS and WOMAC before treatment and 6 months after treatment between two groups(P>0.05). CONCLUSION: For patients with moderate-severe KOA, there is no significant difference in therapeutic effect between compound betamethasone injection and compound betamethasone combined with hyaluronic acid injection, and long-term effect of two methods is not good.
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Ácido Hialurônico , Osteoartrite do Joelho , Betametasona , Criança , Pré-Escolar , Feminino , Humanos , Injeções Intra-Articulares , Masculino , Osteoartrite do Joelho/tratamento farmacológico , Estudos Prospectivos , Resultado do TratamentoRESUMO
The metabolites of salvianolic acid A and salvianolic acid B in rats were analyzed and compared by ultra-high-perfor-mance liquid chromatography with linear ion trap-orbitrap mass spectrometry(UHPLC-LTQ-Orbitrap MS). After the rats were administrated by gavage, plasma at different time points and urine within 24 hours were collected to be treated by solid phase extraction(SPE), then they were gradient eluted by Acquity UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 µm) and 0.1% formic acid solution(A)-acetonitrile(B) mobile phase system, and finally all biological samples of rats were analyzed under negative ion scanning mode. By obtaining the accurate relative molecular mass and multi-level mass spectrometry information of metabolites, combined with the characteristic cleavage law of the reference standard and literature reports, a total of 30 metabolites, including salvianolic acid A and B, were identified. Among them, there were 24 metabolites derived from salvianolic acid A, with the main metabolic pathways including ester bond cleavage, dehydroxylation, decarboxylation, hydrogenation, methylation, hydroxylation, sulfonation, glucuronidation, and their multiple reactions. There were 15 metabolites of salvianolic acid B, and the main biotransformation pathways were five-membered ring cracking, ester bond cleavage, decarboxylation, dehydroxylation, hydrogenation, methylation, sulfonation, glucuronidation, and their compound reactions. In this study, the cross-metabolic profile of salvianolic acid A and B was elucidated completely, which would provide reference for further studies on the basis of pharmacodynamic substances and the exploration of pharmacological mechanism.
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Tecnologia , Animais , Benzofuranos , Ácidos Cafeicos , Cromatografia Líquida de Alta Pressão , Lactatos , Espectrometria de Massas , RatosRESUMO
Intervertebral disc degeneration (IDD) is a common chronic disease characterized by the loss of extracellular matrix (ECM) in the nucleus pulposus (NP). Accumulating evidence has revealed that abnormal expression of microRNAs (miRs) is closely associated with IDD development. The present study aimed to investigate the precise role and possible mechanism underlying the effects of miR6545p in the pathogenesis of IDD. NP cells were isolated from patients with IDD. Monodansylcadaverine staining was conducted to reveal cell autophagy, while western blotting was performed to detect the expression of ECMrelated proteins in NP cells. Luciferase reporter and RNA immunoprecipitation assays were conducted to identify the binding between RNAs. The results demonstrated that miR6545p was significantly upregulated in degenerated NP tissues from patients with IDD and high miR6545p expression was positively associated with disc degeneration grade. Functional assays suggested that miR6545p facilitated ECM degradation by increasing the expression levels of MMP3, MMP9 and MMP13, as well as decreasing collagen I, collagen II, SOX9 and aggrecan expression by inhibiting autophagy. Furthermore, autophagyrelated gene 7 (ATG7) was verified as a direct downstream target gene of miR6545p. miR6545p could bind to the 3' untranslated region of ATG7 to inhibit its mRNA expression and further reduce its translation. Notably, ATG7 knockdown abrogated the effects of the miR6545p inhibitor on ECM degradation and autophagy regulation. Furthermore, miR6545p inhibited autophagy in NP cells by increasing the protein expression levels of phosphorylated (p)PI3K, pAKT and pmTOR in an ATG7dependent manner. In conclusion, the results of the present study revealed that miR6545p may enhance ECM degradation via inhibition of autophagy by targeting ATG7 to activate the PI3K/AKT/mTOR signaling pathway. These findings may provide novel insights into the treatment of IDD.
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Proteína 7 Relacionada à Autofagia/metabolismo , Autofagia/efeitos dos fármacos , Degeneração do Disco Intervertebral/metabolismo , MicroRNAs/farmacologia , Transdução de Sinais/efeitos dos fármacos , Serina-Treonina Quinases TOR/metabolismo , Adulto , Agrecanas/metabolismo , Matriz Extracelular/metabolismo , Proteínas da Matriz Extracelular , Feminino , Humanos , Masculino , Metaloproteinase 13 da Matriz , Metaloproteinase 3 da Matriz , MicroRNAs/genética , Pessoa de Meia-Idade , Núcleo Pulposo/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Regulação para CimaRESUMO
We present a novel method to jointly learn a 3D face parametric model and 3D face reconstruction from diverse sources. Previous methods usually learn 3D face modeling from one kind of source, such as scanned data or in-the-wild images. Although 3D scanned data contain accurate geometric information of face shapes, the capture system is expensive and such datasets usually contain a small number of subjects. On the other hand, in-the-wild face images are easily obtained and there are a large number of facial images. However, facial images do not contain explicit geometric information. In this paper, we propose a method to learn a unified face model from diverse sources. Besides scanned face data and face images, we also utilize a large number of RGB-D images captured with an iPhone X to bridge the gap between the two sources. Experimental results demonstrate that with training data from more sources, we can learn a more powerful face model.
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Face/diagnóstico por imagem , Imageamento Tridimensional/métodos , Bases de Dados Factuais , Feminino , Humanos , Masculino , SmartphoneRESUMO
Mutations in the DNAJB6 gene have been identified as rare causes of myofibrillar myopathies. However, the underlying pathophysiologica mechanisms remain elusive. DNAJB6 has two known isoforms, including the nuclear isoform DNAJB6a and the cytoplasmic isoform DNAJB6b, which was thought to be the pathogenic isoform. Here, we report a novel recessive mutation c.695_699del (p. Val 232 Gly fs*7) in the DNAJB6 gene, associated with an apparently recessively inherited late onset distal myofibrillar myopathy in a Chinese family. Notably, the novel mutation localizes to exon 9 and uniquely encodes DNAJB6a. We further identified that this mutation decreases the mRNA and protein levels of DNAJB6a and results in an age-dependent recessive toxic effect on skeletal muscle in knock-in mice. Moreover, the mutant DNAJB6a showed a dose-dependent anti-aggregation effect on polyglutamine-containing proteins in vitro. Taking together, these findings reveal the pathogenic role of DNAJB6a insufficiency in myofibrillar myopathies and expand upon the molecular spectrum of DNAJB6 mutations.
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Miopatias Distais/genética , Proteínas de Choque Térmico HSP40/genética , Chaperonas Moleculares/genética , Músculo Esquelético/patologia , Músculo Esquelético/fisiopatologia , Mutação , Miopatias Congênitas Estruturais/genética , Proteínas do Tecido Nervoso/genética , Idoso , Animais , Povo Asiático , Miopatias Distais/diagnóstico por imagem , Miopatias Distais/patologia , Miopatias Distais/fisiopatologia , Técnicas de Introdução de Genes , Células HEK293 , Proteínas de Choque Térmico HSP40/metabolismo , Proteínas de Choque Térmico HSP40/fisiologia , Humanos , Masculino , Camundongos , Camundongos Transgênicos , Chaperonas Moleculares/metabolismo , Chaperonas Moleculares/fisiologia , Miopatias Congênitas Estruturais/diagnóstico por imagem , Miopatias Congênitas Estruturais/patologia , Miopatias Congênitas Estruturais/fisiopatologia , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/fisiologia , FenótipoRESUMO
Swertiamarin, a natural ingredient with potent pharmacological activities in the iridoid glycoside family, had been reported to have significant therapeutic effects on a variety of human diseases.In this study, a systematic and efficient strategy based on UHPLC-Q-Exactive Orbitrap mass spectrometry was established to reveal the metabolic profile of swertiamarin in rat urine, plasma, and faeces.First of all, post-acquisition data-mining methods, including multiple mass defect filters (MMDFs) and high-resolution extracted ion chromatograms (HREICs), were developed to screen the metabolite candidates of swertiamarin from the complete mass scan data sets.Second, according to the diagnostic product ions (DPIs), neutral loss fragments (NLFs), chromatographic retention time, accurate mass measurement and calculated Clog P values, all metabolite candidates were rapidly identified.As a consequence, 49 metabolites altogether, including archetype compound, were preliminarily characterised. The corresponding in vivo biotransformation processes, such as dehydration, dehydrogenation, hydroxylation, hydrogenation, methylation, sulphonation, N-acetylcysteine (NAC) formation, N-heterocyclisation and their composite reactions, were all discovered in the study.In conclusion, our results not only detailedly elucidated many new metabolites and metabolic pathways of swertiamarin, but also provided a reference for further study of its pharmacological mechanism and evaluation of its safety.
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Glucosídeos Iridoides , Espectrometria de Massas por Ionização por Electrospray , Animais , Cromatografia Líquida de Alta Pressão , Pironas , Ratos , Ratos Sprague-DawleyRESUMO
OBJECTIVE: To investigate the effect of continuous adductor block on pain control after bilateral knee joint â stage replacement. METHODS: A retrospective analysis was made of the data of 24 patients with bilateral knee joint I stage replacement who were treated in our hospital from January 2018 to January 2019, and who underwent continuous adductor block analgesia. There were 6 males and 18 females, aged 60 to 72 (65.05±5.82) years old. The patients underwent continuous block of adductor canal with patient-controlled analgesia system. At 4, 6, 12, 24, 36 and 48 hours after operation, visual analogue score(VAS) of resting state and passive motion state was performed;the knee joint activity was followed up for 1 week, 1, 3 and 6 months after operation;the knee joint function was scored at 6 months after operation, using the knee joint scoring standard of American Special Surgery Hospital(HSS);adverse reactions and complications were recorded. RESULTS: The VAS scores under resting state and passive motion state at each time point were less than 3 points in patients with continuous adductor block. The patients had better postoperative exercise of knee joint activity. The score of HSS was excellent in 20 cases, good in 2 cases, fair in 1 case and poor in 1 case. There were only 4 cases of nausea and vomiting, none of them had serious adverse reactions and complications such as bradycardia and deep vein thrombosis. CONCLUSION: Continuous adductor block has a significant effect on pain control and less adverse reactions after bilateral knee jointâ -stage replacement.
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Artroplastia do Joelho , Bloqueio Nervoso , Idoso , Artroplastia do Joelho/efeitos adversos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Manejo da Dor , Dor Pós-Operatória , Estudos RetrospectivosRESUMO
Phillyrin, a well-known bisepoxylignan, has been shown to have many critical pharmacological activities. In this study, a novel strategy for the extensive acquisition and use of data was established based on UHPLC-Q-Exactive mass spectrometry to analyze and identify the in vivo metabolites of phillyrin and to elucidate the in vivo metabolic pathways of phillyrin. Among them, the generation of data sets was mainly due to multichannel data mining methods, such as high extracted ion chromatogram (HEIC), diagnostic product ion (DPI), and neutral loss filtering (NLF). A total of 60 metabolites (including the prototype compound) were identified in positive and negative ion modes based on intuitive and useful data such as the standard's cleavage rule, accurate molecular mass, and chromatographic retention time. The results showed that a series of biological reactions of phillyrin in vivo mainly included methylation, hydroxylation, hydrogenation, sulfonation, glucuronidation, demethylation, and dehydrogenation and their composite reactions. In summary, this study not only comprehensively explained the in vivo metabolism of phillyrin, but also proposed an effective strategy to quickly analyze and identify the metabolites of natural pharmaceutical ingredients in nature.
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Muscle wasting and diminished physical performance contribute to the morbidity and mortality of chronic kidney disease (CKD), for which no curative therapy exists. Accumulating evidence indicates that impaired angiogenesis occurs in the muscles of CKD models. Therefore, proangiogenesis therapy is considered a potentially effective strategy for limiting CKD-associated myopathy. Hypoxia-inducible factor (HIF)-prolyl hydroxylase inhibitor (HIF-PHI) stabilizes HIF and enhances muscle angiogenesis during acute ischemia; however, little evidence was available from CKD models. Here, we assessed whether pharmacological activation of HIF by MK-8617 (MK), a novel orally active HIF-PHI, improves CKD-associated myopathy. Mice were divided into sham or CKD groups, and CKD mice were subdivided into CKD + vehicle or MK treatment groups (1.5, 5, or 12.5 mg/kg for 12 wk). In CKD mice, skeletal muscle mass, mitochondrial amount, and exercise capacity decreased compared with sham mice. Compared with the CKD + vehicle group, low (1.5 mg/kg) and medium (5 mg/kg) doses of MK, but not the high dose (12.5 mg/kg), significantly restored these changes and was accompanied by incremental increases in HIF-1α. Furthermore, increased capillary density and area were observed in a MK dose-dependent manner, which is likely related to an improved VEGF response in the skeletal muscle of CKD mice. In addition, macrophage and proinflammatory cytokines, including monocyte chemoattractant protein 1, TNF-α, and IL-6, significantly increased in the high-dose MK group. These results indicate that HIF-PHI provides a potential therapeutic strategy to improve CKD-associated myopathy.
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Fator 1 Induzível por Hipóxia/antagonistas & inibidores , Doenças Musculares/tratamento farmacológico , Doenças Musculares/etiologia , Inibidores de Prolil-Hidrolase/farmacologia , Piridazinas/farmacologia , Pirimidinas/farmacologia , Insuficiência Renal Crônica/complicações , Administração Oral , Animais , Imuno-Histoquímica , Camundongos , Camundongos Endogâmicos C57BL , Força Muscular/efeitos dos fármacos , Músculo Esquelético/patologia , Doenças Musculares/patologia , Piridazinas/administração & dosagem , Pirimidinas/administração & dosagemRESUMO
Lakes of meltwater in the Artic have become one of the transforming landscape changes under global warming. We herein compared microbial communities between sediments and bank soils at an arctic lake post land submergence using geochemistry, 16S rRNA amplicons, and metagenomes. The results obtained showed that each sample had approximately 2,609 OTUs on average and shared 1,716 OTUs based on the 16S rRNA gene V3-V4 region. Dominant phyla in sediments and soils included Proteobacteria, Acidobacteria, Actinobacteria, Gemmatimonadetes, and Nitrospirae; sediments contained a unique phylum, Euryarchaeota, with the phylum Thaumarchaeota being primarily present in bank soils. Among the top 35 genera across all sites, 17 were more abundant in sediments, while the remaining 18 were more abundant in bank soils; seven out of the top ten genera across all sites were only from sediments. A redundancy analysis separated sediment samples from soil samples based on the components of nitrite and ammonium. Metagenome results supported the role of nitrite because most of the genes for denitrification and methane metabolic genes were more abundant in sediments than in soils, while the abundance of phosphorus-utilizing genes was similar and, thus, was not a significant explanatory factor. We identified several modules from the global networks of OTUs that were closely related to some geochemical factors, such as pH and nitrite. Collectively, the present results showing consistent changes in geochemistry, microbiome compositions, and functional genes suggest an ecological mechanism across molecular and community levels that structures microbiomes post land submergence.
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Sedimentos Geológicos/microbiologia , Metagenômica , Microbiota , Microbiologia do Solo , Archaea/classificação , Archaea/genética , Proteínas Arqueais/genética , Proteínas Arqueais/metabolismo , Regiões Árticas , Bactérias/classificação , Bactérias/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Biodiversidade , Sedimentos Geológicos/química , Lagos , Metano/metabolismo , Microbiota/genética , Nitrogênio/metabolismo , RNA Ribossômico 16S/genética , Solo/químicaRESUMO
BACKGROUND: Platelet-rich plasma (PRP) is a promising strategy for intervertebral disc degeneration. However, the potential harmful effects of leukocytes in PRP on nucleus pulposus-derived mesenchymal stem cells (NPMSCs) have seldom been studied. This study aimed at comparatively evaluating effects of pure platelet-rich plasma (P-PRP) and leukocyte-containing platelet-rich plasma (L-PRP) on rabbit NPMSCs in vitro. METHODS: NPMSCs isolated from rabbit NP tissues were treated with L-PRP or P-PRP in vitro, and then cell proliferation and expression of stem cell markers, proinflammatory cytokines (TNF-α, IL-1ß), production of ECM (extracellular matrix-related protein), and NF-κB p65 protein were validated by CCK-8 assay, real-time polymerase chain reaction, enzyme-linked immunosorbent assay, immunofluorescence, and western blot respectively. RESULTS: NPMSCs differentiate into nucleus pulposus-like cells after treatment of PRPs (P-PRP and L-PRP), and NPMSCs exhibited maximum proliferation at a 10% PRP dose. L-PRP had observably higher concentration of leukocytes, TNF-α, and IL-1ß than P-PRP. Furthermore, compared to P-PRP, L-PRP induced the differentiated NPMSCs to upregulate the expression of TNF-α and IL-1ß, enhanced activation of the NF-κB pathway, increased the expression of MMP-1 and MMP-13, and produced less ECM in differentiated NPMSCs. CONCLUSIONS: Both P-PRP and L-PRP can induce the proliferation and NP-differentiation of NPMSCs. Compared to L-PRP, P-PRP can avoid the activation of the NF-κB pathway, thus reducing the inflammatory and catabolic responses.
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The recombinant adeno-associated virus human thioredoxin-PR39 (rAAV/hTRX-PR39) has been demonstrated to have a protective effect on hypoxic cells. The present study aimed to explore the potential effect of rAAV/hTRX-PR39 on acute cerebral infarction in rats. Middle cerebral artery occlusion (MCAO) model rats were produced and divided into three groups: Normal saline group, empty virus group (rAAV, without hTRX-PR39 cDNA) and rAAV/hTRX-PR39 group. Hematoxylin and eosin staining and electron microscopy observation were used to assess the morphological changes of ischemic brain tissue during different periods. Immunohistochemistry was employed to detect the expression of CD34 to reflect angiogenesis of ischemic brain tissue. Rats treated with rAAV/hTRX-PR39 showed an alleviated degree of ischemic brain edema relative to that in control groups, suggesting PR39 can ameliorate brain damage after cerebral ischemia. In the rAAV/hTRX-PR39 group, CD34-positive cells were significantly increased in ischemic brain tissues compared to control groups. Furthermore, CD34-positive cells were primarily observed around the perivascular in ischemic brain, indicating the angiogenesis role of PR39 in ischemic brain. The present findings suggest that PR39 could effectively ameliorate ischemic brain damage and promote angiogenesis, which may contribute to the treatment of acute cerebral infarction.
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The aim of the present study was to investigate whether the co-injection of hyaluronic acid (HA) and corticosteroids (CS) was superior to HA alone in the treatment of knee OA. A total of 120 participants with symptomatic knee OA were recruited and formed the intention-to-treat population for a 6-month follow-up. In the HA group, patients received a single-shot injection of 4 ml HA. In the HA&CS group, patients received a co-injection of 3 ml compound betamethasone solution and 4 ml HA. Visual analog scale (VAS), Western Ontario and McMaster University Osteoarthritis Index (WOMAC) and knee flexion motion were assessed as primary outcomes. Patients in the HA&CS group exhibited better pain relief and knee function at the time points of week 1, month 1 and month 3 (P<0.05). For the last follow-up at month 6, the values did not differ significantly between these two groups. Patients in both groups exhibited improvement in pain, knee function, and range of motion following injection. For the final follow-up at month 6, the mean VAS score, WOMAC score and knee flexion motion were still superior to that prior to treatment, but the values did not differ significantly. The co-injection of HA and CS provided a rapid improvement in pain relief, knee function, and range of motion, but did not differ significantly from that of HA alone in the long term effect.
RESUMO
Expansion of penguin activity in maritime Antarctica, under ice thaw, increases the chances of penguin feces affecting soil microbiomes. The detail of such effects begins to be revealed. By comparing soil geochemistry and microbiome composition inside (one site) and outside (three sites) of the rookery, we found significant effects of penguin feces on both. First, penguin feces change soil geochemistry, causing increased moisture content (MC) of ornithogenic soils and nutrients C, N, P, and Si in the rookery compared to non-rookery sites, but not pH. Second, penguin feces directly affect microbiome composition in the rookery, not those outside. Specifically, we found 4,364 operational taxonomical units (OTUs) in 404 genera in six main phyla: Proteobacteria, Actinobacteria, Gemmatimonadetes, Acidobacteria, Chloroflexi, and Bacteroidetes. Although the diversity is similar among the four sites, the composition is different. For example, penguin rookery has a lower abundance of Acidobacteria, Chloroflexi, and Nitrospirae but a higher abundance of Bacteroidetes, Firmicutes, and Thermomicrobia. Strikingly, the family Clostridiaceae of Firmicutes of penguin-feces origin is most abundant in the rookery than non-rookery sites with two most abundant genera, Tissierella and Proteiniclasticum. Redundancy analysis showed all measured geochemical factors are significant in structuring microbiomes, with MC showing the highest correlation. We further extracted 21 subnetworks of microbes which contain 4,318 of the 4,364 OTUs using network analysis and are closely correlated with all geochemical factors except pH. Our finding f penguin feces, directly and indirectly, affects soil microbiome suggests an important role of penguins in soil geochemistry and microbiome structure of maritime Antarctica.