RESUMEN
OBJECTIVES: To unravel the heterogeneity and function of microenvironmental neutrophils during intervertebral disc degeneration (IDD). METHODS: Single-cell RNA sequencing (scRNA-seq) was utilized to dissect the cellular landscape of neutrophils in intervertebral disc (IVD) tissues and their crosstalk with nucleus pulposus cells (NPCs). The expression levels of macrophage migration inhibitory factor (MIF) and ACKR3 in IVD tissues were detected. The MIF/ACKR3 axis was identified and its effects on IDD were investigated in vitro and in vivo. RESULTS: We sequenced here 71520 single cells from 5 control and 9 degenerated IVD samples using scRNA-seq. We identified a unique cluster of neutrophils abundant in degenerated IVD tissues that highly expressed MIF and was functionally enriched in extracellular matrix organization (ECMO). Cell-to-cell communication analyses showed that this ECMO-neutrophil subpopulation was closely interacted with an effector NPCs subtype, which displayed high expression of ACKR3. Further analyses revealed that MIF was positively correlated with ACKR3 and functioned via directly binding to ACKR3 on effector NPCs. MIF inhibition attenuated degenerative changes of NPCs and extracellular matrix, which could be partially reversed by ACKR3 overexpression. Clinically, a significant correlation of high MIF/ACKR3 expression with advanced IDD grade was observed. Furthermore, we also found a positive association between MIF+ ECMO-neutrophil counts and ACKR3+ effector NPCs density as well as higher expression of the MIF/ACKR3 signaling in areas where these two cell types were neighbors. CONCLUSIONS: These data suggest that ECMO-neutrophil promotes IDD progression by their communication with NPCs via the MIF/ACKR3 axis, which may shed light on therapeutic strategies.
RESUMEN
BACKGROUND: Synovial chondromatosis (SC) primarily affects the major joints and is characterized by the formation of benign cartilaginous nodules. In the present study, we evaluated the differences in the histology and gene expression of SC and normal cartilages and further elucidated the function of hub genes in SC. METHODS: Histological staining and biochemical analysis were performed to measure collagen and glycosaminoglycan (GAG) contents in SC and normal cartilage samples. Then, microarray analysis was performed using knee joint samples (three normal and three SC samples) to identify the differentially expressed genes (DEGs). Subsequently, bioinformatics analysis was performed to identify the hub genes and explore the mechanisms underlying SC. The intersection of the top 10 upregulated DEGs, top 10 downregulated DEGs, and hub genes was validated in SC tissues. Lastly, in vitro experiments and our clinical cohort were used to determine the potential biological functions and diagnostic value, respectively, of the most significant gene. RESULTS: The GAG and collagen contents were comparable to or higher in SC tissues than in normal tissues. Microarray analysis revealed 143 upregulated and 107 downregulated DEGs in SC. Furthermore, functional enrichment analysis revealed an association between immunity and metabolism-related pathways and SC development. Among 20 hub genes, two intersection genes, namely, collagen type III alpha 1 chain (COL3A1) and HSPA8, were notably expressed in SC tissues, with COL3A1 exhibiting a more significant difference in mRNA expression. Furthermore, COL3A1 can promote chondrocyte migration and cell cycle progression. Additionally, clinical data revealed COL3A1 can be a diagnostic marker for primary SC (AUC = 0.82) and be a positive correlation with neutrophil-to-lymphocyte ratio. CONCLUSIONS: These results suggest that SC tissues contained the abundant GAG and collagen. COL3A1 can affect the function of chondrocytes and be a diagnostic marker of primary SC patients. These findings provide a novel approach and a fundamental contribution for diagnosis and treatment in SC.
Asunto(s)
Condrocitos , Condromatosis Sinovial , Humanos , Condrocitos/patología , Condromatosis Sinovial/patología , Biomarcadores , Ciclo Celular/genética , Colágeno , Biología Computacional/métodos , Colágeno Tipo IIIRESUMEN
Intervertebral disc degeneration (IDD) constitutes the pathological foundation of most musculoskeletal disorders of the spine. Previous studies have noted that cell proliferation is a common feature of IDD. Bioinformatics indicated that aberrantly expressed long non-coding RNAs (lncRNAs) were involved in the development of IDD. In this study, we aimed to investigate the function of lncRNA HOTAIR in the proliferation of human nucleus pulposus (NP) cells of IDD in vitro and further clarified its mechanism. The expression of HOTAIR and miR-130b was quantified by qRT-PCR in nucleus pulposus (NP) tissues. Furthermore, NP cells proliferation were assayed by CCK8 and Immunostaining. Dual-luciferase reporter and RIP assay were used to examine the expression of HOTAIR, PTEN, and their co-target gene miR-130b. Western blotting was used to test AKT expression. Our in vitro experiments on human normal NP cells observed that HOTAIR was significantly dysregulated in IDD. Further, HOTAIR can suppress proliferation by directly targeting miR-130b. In addition, Both HOTAIR and PTEN were confirmed to target miR-130b, and miR-130b upregulation reversed the phenomenon of ectopic expression of HOTAIR. More importantly, HOTAIR upregulation significantly reduced CyclinD1 protein expression by PTEN/AKT signaling pathway. Our findings suggest that HOTAIR may bind to miR-130b and subsequently increased CyclinD1 expression via PTEN/Akt pathway. Thereby, HOTAIR could become a potential target for the treatment of IDD.Abbreviations : IDD; intervertebral disc degeneration ncRNAs; non-coding RNAs lncRNAs; long non-coding RNAs miRNAs; microRNAs NP; nucleus pulposus qRT-PCR; quantitative reverse transcription-PCR LBP; Low back pain ORF; open reading frame HOTAIR; Hox transcript antisense intergenic RNA FAF1; Fas-associated protein factor-1 Erk; extracellular signal-regulated kinase TUG1; Taurine Up-regulated Gene 1 HIF1A hypoxia-inducible factor 1-alpha PI3K; phosphoinositide-3 kinase AIS; adolescent idiopathic scoliosis ECM; extracellular matrix LN;lupus nephritis CT;computed tomography MRI; magnetic resonance imaging PBS; phosphate-buffered salin PBS; phosphate-buffered salin PVDF; polyvinylidene fluoride TBST; Tris-buffered saline Tween ECL; enhanced chemiluminescence RIP; RNA immunoprecipitation.
Asunto(s)
Degeneración del Disco Intervertebral , MicroARNs , ARN Largo no Codificante/genética , Proteínas Adaptadoras Transductoras de Señales/metabolismo , Adolescente , Apoptosis/genética , Proteínas Reguladoras de la Apoptosis/metabolismo , Proliferación Celular/genética , Humanos , Degeneración del Disco Intervertebral/patología , MicroARNs/metabolismo , Fosfohidrolasa PTEN/genética , Fosfohidrolasa PTEN/metabolismo , Fosfatos/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismoRESUMEN
The employment situation and advantages of interdisciplinary talents of English and acupuncture-moxibustion and tuina at home and abroad are analyzed. The employment rate and further education rate of interdisciplinary talents of English and acupunctue-moxibustion and tuina are higher than those of the normal undergraduates majoring in acupunctue-moxibustion and tuina. The interdisciplinary talents of English and acupuncture-moxibustion and tuina at home are characterized by solid professional foundation and good specialized English, and high comprehensive quality; and the interdisciplinary talents at abroad are characterized by solid professional foundation and good language ability. The interdisciplinary talents of English and acupuncture-moxibustion and tuina should grasp the advantages, cultivate international vision to adapt to international standards, improve the level of clinical practice, promote comprehensive ability, furthermore, improve the employment competitiveness and promote the internationalization of acupuncture- moxibustion and tuina.
Asunto(s)
Terapia por Acupuntura , Acupuntura , Moxibustión , Empleo , LenguajeRESUMEN
This study investigates the catechin composition and protective effect of green tea extract on senescence-mediated redox imbalance in the livers and kidneys of aged mice. The results showed that the seven catechins in the green tea extract analyzed in this study could be completely separated within 30 min and the main components of catechins in green tea extract were EGCG, EGC and ECG. In terms of the anti-senescence effects of green tea extract, green tea extract supplementation at doses of 125, 625 and 1250 mg/kg for 4 weeks significantly alleviated the senescence-mediated redox imbalance, as exhibited from significantly (p < 0.05) reduced thiobarbituric acid-reactive substances (TBARS) and protein carbonyls levels in the serum, and increased glutathione (GSH) and total thiols contents in the plasma. Additionally, hepatic and renal protein carbonyls levels were significantly diminished (p < 0.05) and the activities of superoxide dismutase (SOD), catalase, glucose-6-phosphate dehydrogenase (G6PD), glutathione peroxidase (GSH-Px) and glutathione reductase (GSH-Rd) in the liver and kidney were remarkably elevated (p < 0.05). Overall, these results clearly show that green tea extract exhibits extremely potent protective effects against senescence-mediated redox imbalance in the livers and kidneys of mice by inhibiting oxidative damage of lipids and proteins and increasing the activities of antioxidant enzymes in organs.
Asunto(s)
Antioxidantes , Hígado , Animales , Antioxidantes/metabolismo , Riñón/metabolismo , Peroxidación de Lípido , Hígado/metabolismo , Ratones , Oxidación-Reducción , Estrés Oxidativo , Extractos Vegetales/metabolismo , Extractos Vegetales/farmacología , TéRESUMEN
BACKGROUND: Previous studies have suggested that interleukin (IL)-17A is a key factor that contributes to intervertebral disc degeneration (IDD), whereas autophagy has been shown to be a protective mechanism in IDD. However, the relationship between IL-17A and autophagy in IDD remains to be fully elucidated. This study sought to evaluate the association between IL-17 and autophagy and the potential mechanism through which IL-17A affects autophagy in IDD. METHODS: Intervertebral disc specimens were collected from 10 patients with lumbar disc herniation. Human degenerated nucleus pulposus (NP) cells were cultured in the presence or absence of IL-17A treatment. Western blot and monodansylcadaverine staining were used to measure autophagy levels in human degenerated NP cells. Subsequently, phosphatidylinositol 3-kinase (PI3K)/Akt/Bcl-2 pathway inhibitors were used to reveal the potential mechanism. RESULTS: IL-17A treatment inhibited the autophagic activity in human NP cells in a time- and dose-dependent manner. Moreover, monodansylcadaverine staining showed that cells treated with IL-17A had significantly fewer changes in their autophagic vacuoles compared with control-treated cells. After IL-17A treatment, expression levels of PI3K, p-Akt, and Bcl-2 in NP cells were significantly increased. Further assays with PI3K/Akt/Bcl-2 inhibitors revealed that IL-17A suppressed autophagy in NP cells by activating the PI3K/Akt/Bcl-2 signaling pathway. CONCLUSIONS: These data suggest that IL-17A promotes IDD by inhibiting autophagy through activation of the PI3K/Akt/Bcl-2 signaling pathway and may offer new insights for targeted therapy of this disease.
Asunto(s)
Autofagia/inmunología , Interleucina-17/inmunología , Degeneración del Disco Intervertebral/inmunología , Núcleo Pulposo/inmunología , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Anciano , Autofagia/efectos de los fármacos , Células Cultivadas , Femenino , Humanos , Interleucina-17/farmacología , Degeneración del Disco Intervertebral/metabolismo , Desplazamiento del Disco Intervertebral , Masculino , Persona de Mediana Edad , Núcleo Pulposo/citología , Núcleo Pulposo/metabolismo , Fosfatidilinositol 3-Quinasas/efectos de los fármacos , Fosfatidilinositol 3-Quinasas/farmacología , Inhibidores de las Quinasa Fosfoinosítidos-3 , Fosforilación , Proteínas Proto-Oncogénicas c-akt/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-akt/efectos de los fármacos , Proteínas Proto-Oncogénicas c-bcl-2/antagonistas & inhibidores , Proteínas Proto-Oncogénicas c-bcl-2/efectos de los fármacos , Transducción de SeñalRESUMEN
Obesity is a global public health issue. Thermogenesis is a novel way to promote anti-obesity by consuming energy as heat rather than storing it as triacylglycerols. The browning program allows mitochondrial biosynthesis and thermogenesis-related gene expression to occur in subcutaneous white adipose tissue, which results in the formation of beige adipose tissue. Some phytochemicals have exerted the capability to activate the fat browning process. Resveratrol and oxyresveratrol are both natural stilbenoids that have been reported for their anti-obesity efficacy. However, the comparison between the two as they relate to thermogenesis as well as the differences in their underlying mechanisms are still not widely discussed. Our result reveals that both resveratrol and oxyresveratrol could elevate the expression of thermogenesis-related protein expression including UCP1 (uncoupling protein-1) and PRDM (PR domain containing 16) via Sirt1/PGC-1α (sirtuin 1/peroxisome proliferation gamma coactivator-1 α) activation. However, it is suggested that the transcriptional factor PPARα (peroxisome proliferator-activator receptor α) was activated by resveratrol (1.38 ± 0.07 fold) but not oxyresveratrol. Conversely, C/EBPß (CCAAT/enhancer-binding protein ß) was upregulated by oxyresveratrol (1.58 ± 0.05 fold) but not by resveratrol. On the other hand, CPT1 (carnitine palmitoyltransferase) was found to be significantly activated at lower concentrations of oxyresveratrol up to 1.89 ± 0.04 fold as compared to high-fat diet, and it could be a leading reason for UCP1 activation. Lastly, adiponectin expression was promoted in all experimental groups (1.53 ± 0.08 and 1.49 ± 0.11-fold in resveratrol (RES) and high oxyresveratrol (HOXY), respectively), which could be an activator for mitochondrial biosynthesis and UCP1 expression.
Asunto(s)
Obesidad/tratamiento farmacológico , Obesidad/genética , Resveratrol/administración & dosificación , Termogénesis/efectos de los fármacos , Animales , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Dieta Alta en Grasa/efectos adversos , Metabolismo Energético/efectos de los fármacos , Humanos , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Obesos , Obesidad/metabolismo , Obesidad/fisiopatología , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/genética , Coactivador 1-alfa del Receptor Activado por Proliferadores de Peroxisomas gamma/metabolismo , Sirtuina 1/genética , Sirtuina 1/metabolismo , Factores de Transcripción/genética , Factores de Transcripción/metabolismo , Proteína Desacopladora 1/genética , Proteína Desacopladora 1/metabolismoRESUMEN
BACKGROUND: Liver cirrhosis is an uncommon but not rare side effect of amiodarone-induced hepatotoxicity. Patients with hepatitis B virus and hepatitis C virus infections are at a high risk for developing liver cirrhosis. However, the relationship between this treatment and risk of liver cirrhosis in high-risk chronic hepatitis B and chronic hepatitis C patients is unknown. PATIENTS AND METHODS: The present study identified amiodarone users (N=8,081) from the Taiwan National Health Insurance Research Database from 1997 through 2013. A total of 32,324 subjects with age, comorbidities, gender, and index date-matched non-amiodarone users were selected as controls (non-amiodarone cohort). The incidences of cumulative liver cirrhosis were compared between cohorts. Stratified Cox's regression hazard models were used to assess possible comorbidity-attributable risks for liver cirrhosis. RESULTS: The amiodarone cohort had a nonsignificant risk of liver cirrhosis compared with the non-amiodarone cohort, with a HR of 1.17 (95% CI: 0.93-1.47; P=0.1723). Patients with specific comorbid diseases, including type 2 diabetes mellitus, chronic hepatitis B, chronic hepatitis C, and heart failure, were probably at a high risk of developing liver cirrhosis. The use of statins was associated with a significant 42% reduction in the risk of liver cirrhosis. CONCLUSION: Patients in the amiodarone cohort had no excess risk of liver cirrhosis compared with patients in the non-amiodarone cohort. Long-term surveillance for liver toxicity in high-risk patients with amiodarone treatment is suggested.
RESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Cardiovascular disease is the main concern of breast cancer survivors who received doxorubicin treatment. Traditional Chinese medicine (TCM) provides as a complementary therapy to patients with breast cancer and is an important component of health care in Taiwan. However, the TCM utilization patterns and it's efficacy in breast cancer patients is unknown. MATERIALS AND METHODS: From a sample of claims data collected over the period of 1997-2010 in Taiwan, we identified 24,457 breast cancer patients who received TCM treatments and 24,457 breast cancer patients who did not receive TCM treatments. All enrollment patients had received doxorubicin chemotherapy. These patients were paired by age; index day; and propensity score for selected comorbidities, Herceptin and tamoxifen. The incidence of cumulative congestive heart failure (CHF) was compared between cohorts. Fine and Gray regression hazard model was used to evaluate the risk of CHF. RESULTS: After adjusting for age, Herceptin, tamoxifen, diabetic drug, cardiovascular drug, statin and comorbidities, the stratified Fine and Gray model revealed that the TCM cohort had an adjusted subdistribution hazard ratio (sHR) of 0.68 (95% confidence interval (CI) =â¯0.62-0.76, pâ¯<â¯0.0001) for the development of CHF. In addition, the sub-cohort analysis revealed that the Baihuasheshecao cohort compared to the non-TCM cohort had an adjusted sHR of 0.29 (95% CI = 0.15-0.56, pâ¯=â¯0.0002) for the development of CHF. CONCLUSION: Using TCM significantly decreased the incidence of CHF in patients with breast cancer who received conventional chemotherapy with or without radiotherapy.
Asunto(s)
Antibióticos Antineoplásicos/uso terapéutico , Neoplasias de la Mama/tratamiento farmacológico , Cardiotónicos/uso terapéutico , Doxorrubicina/uso terapéutico , Insuficiencia Cardíaca/prevención & control , Medicina Tradicional China , Adulto , Anciano , Anciano de 80 o más Años , Femenino , Insuficiencia Cardíaca/inducido químicamente , Humanos , Persona de Mediana Edad , Adulto JovenRESUMEN
Oral squamous cell carcinoma (OSCC) is a type of cancer with high morbidity and mortality rates worldwide; it also demonstrates chemotherapeutic resistance. Triterpenoid ursolic acid has been shown to exhibit various biological activities and anticancer effects in several preclinical studies. In our previous study, human cisplatinresistant oral cancer CAR cells were established, and the present study aimed to further examine the effects of ursolic acid on CAR cells. The results revealed that ursolic acid inhibited CAR cell viability, as determined using a 3(4,5dimethylthiazol2yl)2,5diphenyltetrazolium bromide assay. Ursolic acidinduced cell death was mediated through a caspasedependent pathway, determined with the pancaspase inhibitor, zVADfmk. Ursolic acid also increased the activities of caspase3 and caspase9 in CAR cells, determined by a colorimetric assay. Specifically, the production of reactive oxygen species and loss of mitochondrial membrane potential, detected by flow cytometry, were observed in the ursolic acidtreated CAR cells. The apoptosisassociated signaling showed that ursolic acid decreased the phosphorylation of AKT (Ser473) and Bcell lymphoma 2 (Bcl2)associated agonist of cell death (BAD; Ser136), and the protein levels of Bcl2 and Bclextra large (BclxL), and increased the expression of BAD and Bcl2associated X (Bax) protein in CAR cells. In summary, the results supported the potential application of ursolic acid against drugresistant oral carcinoma and to improve oral anticancer efficacy in the near future.
Asunto(s)
Apoptosis/efectos de los fármacos , Cisplatino/farmacología , Resistencia a Antineoplásicos , Neoplasias de la Boca/patología , Proteínas Proto-Oncogénicas c-akt/metabolismo , Triterpenos/farmacología , Proteína Letal Asociada a bcl/metabolismo , Antineoplásicos/farmacología , Biomarcadores de Tumor/metabolismo , Caspasas/metabolismo , Proliferación Celular/efectos de los fármacos , Humanos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Neoplasias de la Boca/tratamiento farmacológico , Neoplasias de la Boca/metabolismo , Fosforilación/efectos de los fármacos , Especies Reactivas de Oxígeno/metabolismo , Células Tumorales Cultivadas , Ácido UrsólicoRESUMEN
BACKGROUND: Knowledge on periprosthetic infection and mortality rate following total knee arthroplasty (TKA) is essential for justifying this treatment in patients with cancer; however, relevant data from population-based studies are lacking. Therefore, we examined 1-year periprosthetic infection, mortality, and 5-year relative survival rates in cancer patients who underwent TKA. METHODS: This is a population-based cohort study based on analysis of the Taiwan National Health Insurance Research Database. We enrolled a total of 2294 cancer patients and 131,849 patients without cancer (control group) who underwent TKA between January 1, 1997, and December 31, 2011. All patients were followed until death, infection, withdrawal from the National Health Insurance, or December 31, 2012. RESULTS: The periprosthetic knee joint infection rate in cancer patients (1.73%) was not significantly higher than that in the control group (1.87%). However, the 1-year mortality rate was significantly higher (p < 0.05) in the cancer group (4.10%) than in the control group (1.66%). The overall 5-year survival rate was 93.10% as compared with those without cancers. CONCLUSION: Low periprosthetic knee joint infection rates and high 5-year relative survival rates indicate the feasibility of TKA in cancer patients. However, the surgeon should take into account a higher mortality rate in the first year following TKA.
Asunto(s)
Artroplastia de Reemplazo de Rodilla/efectos adversos , Neoplasias/complicaciones , Infecciones Relacionadas con Prótesis/epidemiología , Adulto , Anciano , Anciano de 80 o más Años , Artroplastia de Reemplazo de Rodilla/mortalidad , Estudios de Cohortes , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Retrospectivos , Factores de Riesgo , Taiwán , Adulto JovenRESUMEN
Intervertebral disc degeneration (IDD) is the most common cause leading to low back pain, a highly prevalent, costly and crippling condition worldwide. Overexpression of miR-21 has been shown to promote proliferation of nucleus pulposus (NP) cells. However, it remains unclear whether miR-21 can promote the degradation of type II collagen (Col II) and aggrecan, two main extracellular matrix components within the disc. Here, the miRNA microassay assay identified 29 differentially expressed miRNAs in NP tissues from IDD patients compared with healthy controls. Following qRT-PCR validation, miR-21 expression was significantly upregulated in degenerated NP tissues, and showed a positive correlation with disc degeneration grade. Through gain-of-function and loss-of-function studies in human NP cells, miR-21 was shown to inhibit autophagy and then upregulate the expression of matrix metalloproteinase (MMP)-3 and MMP-9, leading to increased degradation of Col II and aggrecan. Mechanistically, phosphatase and tensin homolog (PTEN) was identified as a direct target of miR-21, and activated PTEN/ Akt/mammalian target of rapamycin (mTOR) signaling pathway was involved in miR-21-induced autophagy inhibition and Col II and aggrecan breakdown. Taken together, these results suggest that miR-21 contributes to Col II and aggrecan catabolism by inhibiting autophagy via the PTEN/Akt/mTOR signaling pathway in human NP cells.
Asunto(s)
Matriz Extracelular/genética , Degeneración del Disco Intervertebral/genética , MicroARNs/genética , Núcleo Pulposo/patología , Adolescente , Anciano , Agrecanos/metabolismo , Autofagia/genética , Estudios de Casos y Controles , Colágeno Tipo II/metabolismo , Femenino , Humanos , Degeneración del Disco Intervertebral/patología , Masculino , Persona de Mediana Edad , Núcleo Pulposo/citología , Fosfohidrolasa PTEN/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal/genética , Serina-Treonina Quinasas TOR/metabolismo , Adulto JovenRESUMEN
BACKGROUND/AIM: Gadoxetate disodium (Primovist or Eovist) is extensively used as a hepatospecific contrast agent during magnetic resonance imaging (MRI) examinations. However, there is no information determining whether gadoxetate disodium has a cytotoxic impact and/or affects relative gene expression on liver cells. In the current study, we investigated the effects of gadoxetate disodium on cytotoxicity and the levels of gene expression in human normal Chang Liver cells. MATERIALS AND METHODS: The cytotoxic effect was detected via methyl thiazolyl tetrazolium (MTT) assay and 4',6-diamidino-2-phenylindole (DAPI) staining. mRNA expression was monitored by cDNA microarray and quantitative PCR (qPCR) analysis. The protein levels were determined by western blotting. RESULTS: Gadoxetate disodium at 5 and 10 mM failed to induce any cell cytotoxicity and morphological changes in Chang Liver cells. Our data demonstrated that gadoxetate disodium significantly enhanced the expression of 29 genes and suppressed that of 27. The SLCO1C1 (solute carrier organic anion transporter family member 1C1) mRNA expression was also increased by 2.62-fold (p-value=0.0006) in gadoxetate disodium-treated cells. Furthermore, we also checked and found that gadoxetate disodium up-regulated organic anion transporter polypeptide 1B1 (OATP1B1) protein level and increased OATP uptake transporter gene SLCO1C1 mRNA expression. CONCLUSION: Our results provide evidence regarding that gadoxetate disodium might be no cytotoxic effects on liver cells.
Asunto(s)
Medios de Contraste/farmacología , Gadolinio DTPA/farmacología , Hepatocitos/efectos de los fármacos , Hepatocitos/metabolismo , Transportador 1 de Anión Orgánico Específico del Hígado/genética , Hígado/diagnóstico por imagen , Hígado/metabolismo , Línea Celular , Supervivencia Celular/efectos de los fármacos , Biología Computacional/métodos , Medios de Contraste/química , Gadolinio DTPA/química , Perfilación de la Expresión Génica , Regulación de la Expresión Génica/efectos de los fármacos , Ontología de Genes , Humanos , Transportador 1 de Anión Orgánico Específico del Hígado/metabolismo , Imagen por Resonancia Magnética/métodos , TranscriptomaRESUMEN
AIM: To investigate the anti-fibrosis effect of rosmarinic acid (RA) in pterygium epithelial cells (PECs) to determine if RA is a potent agent for treating pterygium. METHODS: The PECs (1×104 cells/mL) were treated with 100 µmol/L of RA for 1, 3 and 6h. After RA treatment, the cell viability was determined by staining with acridine orange/DAPI and analysis via a NucleoCounter NC-3000. The protein expression levels of type I collagen, transforming growth factor beta-1 (TGF-ß1), TGF-ß type II receptor (TGF-ßRII), p-Smad1/5, p-Smad2, p-Smad3, and Smad4 of the cell lysates were measured by Western blot analysis. RESULTS: The cell viability of PECs was significantly decreased after RA treatment (P<0.01). As the result, RA reduced the protein expression of type I collagen and TGF-ß1 of PECs. Additionally, RA also inhibited TGF-ß1/Smad signaling by decreasing the protein expressions of TGF-ßRII, p-Smad1/5, p-Smad2, p-Smad3, and Smad4. CONCLUSION: This study demonstrate that RA could inhibit fibrosis of PECs by down-regulating type I collagen expression and TGF-ß1/Smad signaling. Therefore, RA is a potent therapeutic agent for the treatment of pterygium.
RESUMEN
BACKGROUND: Cisplatin is a potent chemotherapeutic drug for cancer therapy, but it has serious side effects in clinical treatment, particularly nephrotoxicity. The purpose of this study was to evaluate the protective effect of electrolyzed reduced water (ERW) on renal injury caused by cisplatin. METHODS: Animals were divided into four groups as follows: normal control group, cisplatin control group, ERW control group and ERW + cisplatin group. Each group comprised 10 animals, which were orally treated with normal saline or ERW daily companion by administration of one dose of cisplatin for 28 days. Animals in the cisplatin group received an intraperitoneal single-dose injection of cisplatin (20 mg/kg body weight) as a single i.p. dose on the 25th day of the experiment. We determined the hydration state in urine and the level of serum markers of kidney function, the levels of glutathione (GSH) and thiobarbituric acid-reactive substances (TBARS) levels and the activities of glutathione peroxidase (GPx), glutathione reductase (GR), catalase (CAT) and superoxidase dismutase (SOD) in kidney and histopathological changes. RESULTS: After administration of ERW, the reduced urinary osmolality was increased and elevated Na+, K+, Mg2+ and Ca2+ levels in urine were significantly decreased in cisplatin-induced renal injury mice. Besides, the results demonstrated that significantly decreased elevated serum levels of creatinine and blood urea nitrogen (BUN) and the levels of TBARS in the kidneys that were induced by cisplatin. Moreover, ERW treatment was also found to markedly increase (p < 0.05) the activities of GPx, GR, CAT and SOD, and to increase GSH content in the kidneys. Histopathology showed that ERW protects against cisplatin-induced renal injury to both the proximal and distal tubules. CONCLUSION: ERW exhibits potent nephroprotective effects on cisplatin-induced kidney damage in mice, likely due to both the increase in antioxidant-defense system activity and the inhibition of lipid peroxidation.
Asunto(s)
Cisplatino/toxicidad , Riñón/efectos de los fármacos , Agua/farmacología , Animales , Electrólisis , Glutatión/metabolismo , Riñón/metabolismo , Riñón/patología , Peroxidación de Lípido/efectos de los fármacos , Masculino , Ratones , Ratones Endogámicos ICR , Sustancias Protectoras/farmacologíaRESUMEN
Intervertebral disc degeneration (IDD) is thought to be the most common cause of low back pain. Dysregulation of microRNAs (miRNAs) is involved in the development of IDD. The aim of this study was to explore the influence of miR-210 on type II collagen (Col II) and aggrecan expression and possible mechanisms in human degenerated nucleus pulposus (NP) cells. Our results showed that miR-210 levels were significantly increased in degenerated NP tissues compared with healthy controls, and positively correlated with disc degeneration grade. By gain-of-function and loss-of-function studies in human degenerated NP cells, miR-210 was shown to inhibit autophagy and then upregulate MMP-3 and MMP-13 expression, leading to increased degradation of Col II and aggrecan. Autophagy-related gene 7 (ATG7) was identified as a direct target of miR-210. Knockdown of ATG7 by small interfering RNA (siRNA) abrogated the effects of miR-210 inhibitor on MMP-3, MMP-13, Col II and aggrecan expression. Taken together, these results suggest that miR-210 inhibits autophagy via silencing of ATG7, leading to increased Col II and aggrecan degradation in human degenerated NP cells.
Asunto(s)
Proteína 7 Relacionada con la Autofagia/genética , Autofagia/genética , Matriz Extracelular/metabolismo , Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/patología , MicroARNs/metabolismo , Núcleo Pulposo/patología , Adolescente , Adulto , Anciano , Agrecanos/metabolismo , Proteína 7 Relacionada con la Autofagia/metabolismo , Secuencia de Bases , Colágeno Tipo II/metabolismo , Silenciador del Gen , Humanos , Metaloproteinasa 13 de la Matriz/metabolismo , Metaloproteinasa 3 de la Matriz/metabolismo , MicroARNs/genética , Persona de Mediana Edad , Regulación hacia Arriba/genética , Adulto JovenRESUMEN
This study aimed to determine the efficacy and safety of anterior debridement and reconstruction with anatomical screw-plate fixation in patients with lumbosacral junction tuberculosis (TB).A total of 48 patients (30 males and 18 females) diagnosed with lumbosacral junction TB were included in this study. All patients underwent surgery in our institution from January 2008 to July 2014, using anterior debridement and reconstruction with anatomical screw-plate. Outcome data were evaluated before and after surgery and included lumbosacral angle, Frankel classification, bone fusion, and visual analog scale (VAS) scores.All patients were then followed up for an average of 49.4 months (range, 24-96 months). The mean lumbosacral angle improved from 8.36°â±â5.92° pre-operation to 22.38°â±â4.52° post-operation and 21.13°â±â3.73° during the final follow-up (both Pâ<â.05). Solid vertebral fusion was achieved in all patients after 7.6 months on average (range, 6-12 months). No severe complications appeared during operation and post-operation. Neurological performance and VAS scores were significantly improved compared with pre-operation (Pâ<â.05).Following standard anti-TB chemotherapy, anterior debridement and reconstruction with anatomical screw-plate fixation may be a feasible and effective therapeutical option for lumbosacral junction TB. This procedure can result in satisfactory bone fusion and deformity correction, and effectively restore lumbosacral junction stability.
Asunto(s)
Desbridamiento , Fijación Interna de Fracturas , Región Lumbosacra/cirugía , Procedimientos de Cirugía Plástica , Tuberculosis de la Columna Vertebral/cirugía , Adolescente , Adulto , Anciano , Anciano de 80 o más Años , Placas Óseas , Tornillos Óseos , Desbridamiento/métodos , Femenino , Estudios de Seguimiento , Fijación Interna de Fracturas/instrumentación , Fijación Interna de Fracturas/métodos , Humanos , Región Lumbosacra/diagnóstico por imagen , Masculino , Persona de Mediana Edad , Procedimientos de Cirugía Plástica/métodos , Estudios Retrospectivos , Índice de Severidad de la Enfermedad , Resultado del Tratamiento , Tuberculosis de la Columna Vertebral/diagnóstico por imagen , Adulto JovenRESUMEN
The term long non-coding RNA (lncRNA) refers to a group of RNAs with length more than 200 nucleotides, limited protein-coding potential, and having widespread biological functions, including regulation of transcriptional patterns and protein activity, formation of endogenous small interfering RNAs (siRNAs) and natural microRNA (miRNA) sponges. Intervertebral disc degeneration (IDD) and osteoarthritis (OA) are the most common chronic, prevalent and age-related degenerative musculoskeletal disorders. Numbers of lncRNAs are differentially expressed in human degenerative nucleus pulposus tissue and OA cartilage. Moreover, some lncRNAs have been shown to be involved in multiple pathological processes during OA, including extracellular matrix (ECM) degradation, inflammatory responses, apoptosis and angiogenesis. In this review, we summarize current knowledge concerning lncRNAs, from their biogenesis, classification and biological functions to molecular mechanisms and therapeutic potential in IDD and OA.
Asunto(s)
Degeneración del Disco Intervertebral/genética , Degeneración del Disco Intervertebral/fisiopatología , Osteoartritis/genética , Osteoartritis/fisiopatología , ARN Largo no Codificante/metabolismo , Apoptosis/genética , Matriz Extracelular/genética , Matriz Extracelular/metabolismo , Humanos , Degeneración del Disco Intervertebral/metabolismo , Osteoartritis/metabolismo , Interferencia de ARN , ARN Largo no Codificante/genética , Sinoviocitos/citología , Sinoviocitos/metabolismo , TranscriptomaRESUMEN
BACKGROUND: Electrolyzed acid water (EAW) has been recognized to have strong bactericidal activity, and the feasibility and safety of EAW irrigation in body cavities has been reported in the literature. This study was conducted to evaluate the effect of EAW nasal irrigation on the postoperative care of functional endoscopic sinus surgery (FESS). METHODS: Patients with chronic rhinosinusitis who received FESS for treatment were recruited and randomly assigned to three groups at 1 month postoperatively. Patients in group 1 received EAW for nasal irrigation daily for 2 months, those in group 2 received neutral normal saline (NS) daily for 2 months, and those in group 3 did not receive nasal irrigation after surgery. Before and 3 months after FESS, sinonasal symptoms were assessed by questionnaire and patients received endoscopic examination, acoustic rhinometry, smell test, saccharine transit test, and bacterial culture from middle meatus. RESULTS: There were 185 patients enrolled between May 2009 and March 2012. Among the patients who completed the study, 36 received EWA irrigation, 35 received NS irrigation, and 39 (group 3) received no irrigation. Patients with nasal irrigation had a better outcome based on questionnaire score and saccharine transit time. However, there was no difference in outcome between patients who received irrigation with EAW and NS. CONCLUSION: Our study showed that EWA irrigation did not confer a greater benefit than that of NS irrigation in post-FESS care.
Asunto(s)
Antibacterianos/administración & dosificación , Endoscopía , Peróxido de Hidrógeno/administración & dosificación , Senos Paranasales/efectos de los fármacos , Rinitis/terapia , Sinusitis/terapia , Irrigación Terapéutica , Quimioterapia Adyuvante , Enfermedad Crónica , Humanos , Senos Paranasales/cirugía , Cuidados Posoperatorios , Rinitis/cirugía , Rinometría Acústica , Sinusitis/cirugía , Olfato/efectos de los fármacos , Olfato/genética , Resultado del TratamientoRESUMEN
Green tea is believed to be beneficial to health because it possesses antioxidant, antiviral and anticancer properties. The potential toxicity of green tea when administered at high doses via concentrated extracts, however, has not been completely investigated. The objective of the present study was to evaluate the safety of green tea extract in ICR mice using a subacute exposure paradigm. In this study, mice were orally administered (gavage) green tea extract at doses of 0 (as normal group), 625, 1250 and 2500mg/kgbody weight/day for 28days. The results showed that oral administration of green tea extract did not cause adverse effects on body weight, organ weights, hematology, serum biochemistry, urinalysis or histopathology. Additionally, administering green tea extract via gavage significantly reduced triglyceride and cholesterol levels. These observed effects could be attributed to the high levels of catechins present in green tea as these compounds have been reported to have beneficial health effects. The no-observed-adverse-effect level for green tea extract derived from the results of the present study was 2500mg/kgbody weight/day.