RESUMO
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.
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Condrócitos , Condromatose Sinovial , Humanos , Condrócitos/patologia , Condromatose Sinovial/patologia , Biomarcadores , Ciclo Celular/genética , Colágeno , Biologia Computacional/métodos , Colágeno Tipo IIIRESUMO
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.
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Degeneração do Disco Intervertebral , MicroRNAs , RNA Longo não Codificante/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Adolescente , Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Proliferação de Células/genética , Humanos , Degeneração do Disco Intervertebral/patologia , MicroRNAs/metabolismo , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Fosfatos/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismoRESUMO
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.
Assuntos
Autofagia/imunologia , Interleucina-17/imunologia , Degeneração do Disco Intervertebral/imunologia , Núcleo Pulposo/imunologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Idoso , Autofagia/efeitos dos fármacos , Células Cultivadas , Feminino , Humanos , Interleucina-17/farmacologia , Degeneração do Disco Intervertebral/metabolismo , Deslocamento do Disco Intervertebral , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/citologia , Núcleo Pulposo/metabolismo , Fosfatidilinositol 3-Quinases/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/farmacologia , Inibidores de Fosfoinositídeo-3 Quinase , Fosforilação , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-akt/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-bcl-2/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-bcl-2/efeitos dos fármacos , Transdução de SinaisRESUMO
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.
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Antibióticos Antineoplásicos/uso terapêutico , Neoplasias da Mama/tratamento farmacológico , Cardiotônicos/uso terapêutico , Doxorrubicina/uso terapêutico , Insuficiência Cardíaca/prevenção & controle , Medicina Tradicional Chinesa , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Insuficiência Cardíaca/induzido quimicamente , Humanos , Pessoa de Meia-Idade , Adulto JovemRESUMO
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.
Assuntos
Apoptose/efeitos dos fármacos , Cisplatino/farmacologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Bucais/patologia , Proteínas Proto-Oncogênicas c-akt/metabolismo , Triterpenos/farmacologia , Proteína de Morte Celular Associada a bcl/metabolismo , Antineoplásicos/farmacologia , Biomarcadores Tumorais/metabolismo , Caspases/metabolismo , Proliferação de Células/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Neoplasias Bucais/tratamento farmacológico , Neoplasias Bucais/metabolismo , Fosforilação/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Células Tumorais Cultivadas , Ácido UrsólicoRESUMO
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.
Assuntos
Artroplastia do Joelho/efeitos adversos , Neoplasias/complicações , Infecções Relacionadas à Prótese/epidemiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Artroplastia do Joelho/mortalidade , Estudos de Coortes , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Taiwan , Adulto JovemRESUMO
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.
Assuntos
Matriz Extracelular/genética , Degeneração do Disco Intervertebral/genética , MicroRNAs/genética , Núcleo Pulposo/patologia , Adolescente , Idoso , Agrecanas/metabolismo , Autofagia/genética , Estudos de Casos e Controles , Colágeno Tipo II/metabolismo , Feminino , Humanos , Degeneração do Disco Intervertebral/patologia , Masculino , Pessoa de Meia-Idade , Núcleo Pulposo/citologia , PTEN Fosfo-Hidrolase/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/genética , Serina-Treonina Quinases TOR/metabolismo , Adulto JovemRESUMO
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.
Assuntos
Meios de Contraste/farmacologia , Gadolínio DTPA/farmacologia , Hepatócitos/efeitos dos fármacos , Hepatócitos/metabolismo , Transportador 1 de Ânion Orgânico Específico do Fígado/genética , Fígado/diagnóstico por imagem , Fígado/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Biologia Computacional/métodos , Meios de Contraste/química , Gadolínio DTPA/química , Perfilação da Expressão Gênica , Regulação da Expressão Gênica/efeitos dos fármacos , Ontologia Genética , Humanos , Transportador 1 de Ânion Orgânico Específico do Fígado/metabolismo , Imageamento por Ressonância Magnética/métodos , TranscriptomaRESUMO
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.
Assuntos
Cisplatino/toxicidade , Rim/efeitos dos fármacos , Água/farmacologia , Animais , Eletrólise , Glutationa/metabolismo , Rim/metabolismo , Rim/patologia , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos ICR , Substâncias Protetoras/farmacologiaRESUMO
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.
Assuntos
Desbridamento , Fixação Interna de Fraturas , Região Lombossacral/cirurgia , Procedimentos de Cirurgia Plástica , Tuberculose da Coluna Vertebral/cirurgia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Placas Ósseas , Parafusos Ósseos , Desbridamento/métodos , Feminino , Seguimentos , Fixação Interna de Fraturas/instrumentação , Fixação Interna de Fraturas/métodos , Humanos , Região Lombossacral/diagnóstico por imagem , Masculino , Pessoa de Meia-Idade , Procedimentos de Cirurgia Plástica/métodos , Estudos Retrospectivos , Índice de Gravidade de Doença , Resultado do Tratamento , Tuberculose da Coluna Vertebral/diagnóstico por imagem , Adulto JovemRESUMO
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.
Assuntos
Antibacterianos/administração & dosagem , Endoscopia , Peróxido de Hidrogênio/administração & dosagem , Seios Paranasais/efeitos dos fármacos , Rinite/terapia , Sinusite/terapia , Irrigação Terapêutica , Quimioterapia Adjuvante , Doença Crônica , Humanos , Seios Paranasais/cirurgia , Cuidados Pós-Operatórios , Rinite/cirurgia , Rinometria Acústica , Sinusite/cirurgia , Olfato/efeitos dos fármacos , Olfato/genética , Resultado do TratamentoRESUMO
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.
Assuntos
Camellia sinensis/química , Extratos Vegetais/toxicidade , Animais , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Ingestão de Alimentos/efeitos dos fármacos , Feminino , Hematologia , Histocitoquímica , Masculino , Camundongos , Camundongos Endogâmicos ICR , Nível de Efeito Adverso não Observado , Distribuição Aleatória , Triglicerídeos/sangue , UrináliseRESUMO
Cervical cancer is the second leading cancer affecting women, and recent studies have demonstrated arsenic trioxide (As(2)O(3)) has therapeutic effects on cervical cancer by promoting apoptosis and inhibiting metastasis in vitro and in vivo. Humic acid (HA) possesses various pharmacologic properties, including anti-inflammatory, anti-neoplastic, and anti-proliferative effects by inducing apoptosis. We examined the growth inhibition properties and the combined effects of HA and As(2)O(3) in human cervical adenocarcinoma cell lines. Our results shown both As(2)O(3) and HA-induced inhibition of cell growth, most likely by ROS-mediated cell damage and activation of the apoptosis pathway, and HA enhanced the anti-proliferative action of As(2)O(3) in HeLa and SiHa cells, which reduced the LC(50) about 57.62 or 73.52% (300µg HA/mL) to 83.67 or 79.03% (500µg HA/mL), respectively. This study is relevant to the development of chemotherapeutic approaches using As(2)O(3) in treating human cervical cancer.
RESUMO
The present study examined the protective effects of seabuckthorn (Hippophae rhamnoides L., SBT) seed oil on carbon tetrachloride (CCl(4))-induced hepatic damage in male ICR mice. Our results showed that oral administration of SBT seed oil at doses of 0.26, 1.30, and 2.60 mg/kg for 8 weeks significantly reduced the elevated levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), and cholesterol at least 13% in serum, and the level of malondialdehyde (MDA) in liver at least 22%, that was induced by CCl(4) (1 mL/kg) in mice. Moreover, the treatment of SBT seed oil was also found to significantly increase the activities of superoxide dismutase (SOD), catalase, glutathione peroxidase (GSH-Px), glutathione reductase (GSH-Rd), and GSH content in liver up to 134%. Our study found that the optimal dose of SBT seed oil was 0.26 mg/kg, as the minimum amount exhibiting the greatest hepatoprotective effects on CCl(4)-induced liver injury. Overall, the hepatoprotective effect of SBT seed oil at all tested doses was found to be comparable to that of silymarin (200 mg/kg) and have been supported by the evaluation of the liver histopathology in mice.
Assuntos
Intoxicação por Tetracloreto de Carbono/prevenção & controle , Doença Hepática Crônica Induzida por Substâncias e Drogas/prevenção & controle , Hippophae/química , Óleos de Plantas/uso terapêutico , Administração Oral , Alanina Transaminase/sangue , Fosfatase Alcalina/sangue , Animais , Aspartato Aminotransferases/sangue , Intoxicação por Tetracloreto de Carbono/sangue , Intoxicação por Tetracloreto de Carbono/patologia , Doença Hepática Crônica Induzida por Substâncias e Drogas/sangue , Doença Hepática Crônica Induzida por Substâncias e Drogas/patologia , Modelos Animais de Doenças , Lipídeos/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos ICR , Oxirredutases/metabolismo , Sementes/químicaRESUMO
BACKGROUND: Functional endoscopic sinus surgery (FESS) has been considered to improve the olfactory function in patients with chronic rhinosinusitis. However, which factors might affect the olfactory outcome after FESS has not been well investigated. METHODS: A total of 70 patients with chronic rhinosinusitis who underwent FESS were enrolled in the study. The potential prognostic factors for improvement in olfaction after FESS were evaluated in these patients. On the day before FESS, the olfactory function was evaluated by a symptom score, a phenyl ethyl alcohol odor detection threshold test, the University of Pennsylvania Smell Identification Test, and a short-term odor memory/discrimination test, and were reevaluated by the same methods 6 months after FESS. RESULTS: The degree of nasal obstruction, the second minimal cross-sectional area measured by acoustic rhinometry, computed tomography scores before FESS, the degree of preoperative olfactory loss indicated by threshold and identification scores, and coexistence of nasal polyps or allergic rhinitis were not significantly reliable to influence the rates of olfactory improvement after FESS. CONCLUSION: Degree of nasal obstruction, extent of rhinosinusitis disease, and coexistence of nasal polyps or allergic rhinitis did not predicate the overall possibility of any olfactory improvement after FESS.
Assuntos
Endoscopia/métodos , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Rinite/cirurgia , Sinusite/cirurgia , Olfato/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico , Rinite/fisiopatologia , Limiar Sensorial/fisiologia , Sinusite/fisiopatologia , Adulto JovemRESUMO
Electrolzyed-reduced water (ERW) is a higher pH and lower oxidation-reduction potential water. In the present study, we examined the enhanced effect of ERW in the apoptosis of leukemia cells (HL-60) induced by glutathione (GSH). An enhanced inhibitory effect on the viability of the HL-60 cells was observed after treatment with a combination of ERW with various concentrations of GSH, whereas no cytotoxic effect in normal peripheral blood mononuclear cells was observed. The results of apoptotic related protein indicated that the induction of HL-60 cell death was caused by the induction of apoptosis through upregulation of Bax and downregulation of Bcl-2. The results of further investigation showed a diminution of intracellular GSH levels in ERW, and combination with GSH groups. These results suggest that ERW is an antioxidant, and that ERW, in combination with GSH, has an enhanced apoptosis-inducing effect on HL-60 cells, which might be mediated through the mitochondria-dependent pathway.
Assuntos
Apoptose/efeitos dos fármacos , Eletrólitos/química , Glutationa/farmacologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/patologia , Água/química , Água/farmacologia , Animais , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fragmentação do DNA/efeitos dos fármacos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HL-60 , Humanos , Leucemia/genética , Leucemia/patologia , Mitocôndrias/genética , Oxirredução , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: The olfactory loss in patients with chronic rhinosinusitis has been measured by different methods. However, the results have been variable and it is not clear whether functional endoscopic sinus surgery (FESS) significantly improves olfactory function. This study was performed to evaluate the influences of FESS on olfactory function in patients with chronic rhinosinusitis using three different types of olfactory tests. METHODS: Seventy patients with chronic rhinosinusitis were administered the University of Pennsylvania Smell Identification Test (UPSIT), a single staircase phenyl ethyl alcohol odor detection threshold test (STT), and a short-term odor memory/discrimination test a day before and 6 months after FESS. A questionnaire inquiring about the patients' self-perception of olfactory function was administered also. Independent ratings of the severity of chronic rhinosinusitis before FESS were established from CT scans. RESULTS: Fifty-two (74.3%) of the patients reported that their olfactory function was impaired before surgery, and 68.6% of the patients reported impaired olfactory function after surgery, a difference that was not significant. No meaningful changes in any of the olfactory test scores were noted 6 or more months after FESS. Preoperatively, small correlations between CT scores and the symptom scores (r = 0.278; p = 0.024), threshold scores (r = -0.27; p = 0.031), and UPSIT scores (r = -0.36; p = 0.003) were observed. CONCLUSION: In patients with severe rhinosinusitis, FESS had little impact on the ability to smell, regardless of the method for assessing smell function. Subtle associations between olfactory function and the severity of chronic rhinosinusitis determined by CT were observed, however, preoperatively. The olfactory test measures were correlated with one another both pre- and postoperatively.
Assuntos
Endoscopia , Procedimentos Cirúrgicos Otorrinolaringológicos/métodos , Rinite/fisiopatologia , Sinusite/fisiopatologia , Olfato/fisiologia , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Criança , Doença Crônica , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Rinite/complicações , Rinite/cirurgia , Índice de Gravidade de Doença , Sinusite/complicações , Sinusite/cirurgia , Inquéritos e Questionários , Resultado do TratamentoRESUMO
Hepatocyte growth factor (HGF) and its receptor, Met, known to control invasive growth program have recently been shown to play crucial roles in the survival of breast cancer patients. The diet-derived flavonoids have been reported to possess anti-invasion properties; however, knowledge on the pharmacological and molecular mechanisms in suppressing HGF/Met-mediated tumor invasion and metastasis is poorly understood. In our preliminary study, we use HGF as an invasive inducer to investigate the effect of flavonoids including apigenin, naringenin, genistein and kaempferol on HGF-dependent invasive growth of MDA-MB-231 human breast cancer cells. Results show that apigenin presents the most potent anti-migration and anti-invasion properties by Boyden chamber assay. Furthermore, apigenin represses the HGF-induced cell motility and scattering and inhibits the HGF-promoted cell migration and invasion in a dose-dependent manner. The effect of apigenin on HGF-induced signaling activation involving invasive growth was evaluated by immunoblotting analysis, it shows that apigenin blocks the HGF-induced Akt phosphorylation but not Met, ERK, and JNK phosphorylation. In addition to MDA-MB-231 cells, apigenin exhibits inhibitory effect on HGF-induced Akt phosphorylation in hepatoma SK-Hep1 cells and lung carcinoma A549 cells. By indirect immunofluorescence microscopy assay, apigenin inhibits the HGF-induced clustering of beta 4 integrin at actin-rich adhesive site and lamellipodia through PI3K-dependent manner. Treatment of apigenin inhibited HGF-stimulated integrin beta 4 function including cell-matrix adhesion and cell-endothelial cells adhesion in MDA-MB-231 cells. By Akt-siRNA transfection analysis, it confirmed that apigenin inhibited HGF-promoted invasive growth involving blocking PI3K/Akt pathway. Finally, we evaluated the effect of apigenin on HGF-promoted metastasis by lung colonization of tumor cells in nude mice and organ metastasis of tumor cells in chick embryo. By histological and gross examination of mouse lung and real-time PCR analysis of human alu in host tissues, it showed that apigenin, wortmannin, as well as anti-beta 4 antibody all inhibit HGF-promoted metastasis. These data support the inhibitory effect of apigenin on HGF-promoted invasive growth and metastasis involving blocking PI3K/Akt pathway and integrin beta 4 function.
Assuntos
Apigenina/farmacologia , Neoplasias da Mama/patologia , Fator de Crescimento de Hepatócito/fisiologia , Integrina beta4/fisiologia , Inibidores de Fosfoinositídeo-3 Quinase , Proteínas Proto-Oncogênicas c-akt/antagonistas & inibidores , Animais , Adesão Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Embrião de Galinha , Feminino , Flavanonas/farmacologia , Genisteína/farmacologia , Humanos , Quempferóis/farmacologia , Camundongos , Camundongos Nus , Invasividade Neoplásica , Metástase NeoplásicaRESUMO
Black foot disease (BFD) is a peripheral arterial occlusive disease found among the inhabitants of the southwest coast of Taiwan. Moreover, within the BFD-endemic areas, diabetes mellitus occur at significantly higher rates than in other areas of Taiwan. A high concentration of humic acid (HA), and arsenic (As) are present in the artesian well water from BFD-endemic area. The aim of this paper is to study the diabetogenic effect of the combination of HA and AS. Treatment of HIT-T15 cells with HA, As, or both of them resulted loss of cell viability, apoptosis, depletion of ATP, increment of oxidative stress, activation of caspase 3, and dysfunction of insulin secretion. In addition, the plasma insulin of ICR mice, which were exposed to HA and As in drinking water for 12 weeks, was decreased in the 5, 7, and 12 weeks, and increased at early stage of exposure (3 weeks). The results reported herein reveal that HA and As exert HIT-T15 cell dysfunction and inhibited insulin secretive effects. In addition, the sub-acute peri-pancreatitis and islet damage caused by the infiltration of inflammatory cells after exposure of HA and As in drinking water for 5 weeks. Our study has important implications in the diabetogenic effect of the HA and AS which may be mediated by ROS and further information of the toxicity mechanisms will provide under our progressive studies.
Assuntos
Arsênio/toxicidade , Substâncias Húmicas/toxicidade , Células Secretoras de Insulina/efeitos dos fármacos , Pâncreas/efeitos dos fármacos , Poluentes Químicos da Água/toxicidade , Trifosfato de Adenosina/metabolismo , Animais , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular , Sobrevivência Celular/efeitos dos fármacos , Cricetinae , Diabetes Mellitus/induzido quimicamente , Diabetes Mellitus/metabolismo , Diabetes Mellitus/patologia , Glutationa/metabolismo , Insulina/sangue , Insulina/metabolismo , Secreção de Insulina , Células Secretoras de Insulina/metabolismo , Células Secretoras de Insulina/patologia , Masculino , Camundongos , Camundongos Endogâmicos ICR , Pâncreas/patologia , Espécies Reativas de Oxigênio/metabolismoRESUMO
BACKGROUND: Helicobacter pylori are associated with chronic antral gastritis that is related to duodenal ulcer, gastric ulcer, and probably gastric adenocarcinoma. Infection of H. pylori during childhood is considered an important risk factor for gastric carcinoma in adult life. MATERIALS AND METHODS: To examine the epidemiologic characteristics of H. pylori infection among schoolchildren in central Taiwan, a community-based survey was carried out using stratified sampling in 10 elementary schools and three junior high schools including students and theirs teachers. Serum specimens of 1950 healthy schoolchildren (aged 9-15 years old) and 253 teachers who were randomly sampled were screened for the H. pylori antibodies by enzyme-linked immunosorbent assay. Statistical analysis was performed by using the SPSS for Windows statistical software system. RESULTS: A total of 332 subjects were H. pylori antibodies positive, giving an overall prevalence of 15.1%. The age-specific seropositive rates were 11.0% in 9-12 years age group, 12.3% in 13-15 years age group, and 45.1% in the teacher group. The older the age, the higher the seroprevalence (OR = 11.53; 95% CI = 6.73-19.74; p < .001 for children vs. teachers). There was no difference in the seroprevalence of H. pylori infection by gender, ethnicity, geographical area, socioeconomic level, parental education, sibship size, family members, and source of drinking water. CONCLUSION: The teachers had a much higher prevalence of H. pylori antibodies. The finding suggests that these teachers (adults) might be infected in their early childhood and implies that the poor environmental and hygienic conditions might be responsible for it. It seemed that poor water supply system, sewage disposal, and other environmental hygiene in adult might play some roles in H. pylori infection in Taiwan (before early 1980s).