RESUMO
Activation of vitamin D receptor (VDR) in cancer-associated fibroblasts (CAFs) has been implicated in hesitating tumor progression and chemoresistance of several human malignancies. Yet, the role of VDR in CAF-induced chemotherapy resistance of gastric cancer (GC) cells remains elusive. In this study we first conducted immunohistochemistry analysis on tissue microarrays including 88 pairs of GC and normal mucosa samples, and provided clinical evidence that VDR was mainly expressed in gastric mucous cells but almost invisible in CAFs, and VDR expression was negatively correlated with malignant clinical phenotype and advanced stages, low VDR expression confers to poor overall survival rate of patients with GC. In a co-culture system of primary CAFs and cancer cells, we showed that treatment of HGC-27 and AGS GC cells with VDR ligand calcipotriol (Cal, 500 nM) significantly inhibited CAF-induced oxaliplatin resistance. By using RNA-sequencing and Human Cytokine Antibody Array, we demonstrated that IL-8 secretion from CAFs induced oxaliplatin resistance via activating the PI3K/AKT pathway in GC, whereas Cal treatment greatly attenuated the tumor-supportive effect of CAF-derived IL-8 on GC cells. Taken together, this study verifies the specific localization of VDR in GC tissues and demonstrates that activation of VDR abrogates CAF-derived IL-8-mediated oxaliplatin resistance in GC via blocking PI3K/Akt signaling, suggesting vitamin D supplementation as a potential strategy of enhancing the anti-tumor effect of chemotherapy in GC.
Assuntos
Fibroblastos Associados a Câncer , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/tratamento farmacológico , Neoplasias Gástricas/metabolismo , Oxaliplatina/farmacologia , Oxaliplatina/metabolismo , Oxaliplatina/uso terapêutico , Proteínas Proto-Oncogênicas c-akt/metabolismo , Fibroblastos Associados a Câncer/metabolismo , Fibroblastos Associados a Câncer/patologia , Fosfatidilinositol 3-Quinases/metabolismo , Interleucina-8/metabolismo , Interleucina-8/farmacologia , Interleucina-8/uso terapêutico , Linhagem Celular TumoralRESUMO
The G allele of rs4702 polymorphism has been reported to reduce the production of mature BDNF and FURIN, both of which were closely associated with cognitive functions. Real-time PCR, ELISA and luciferase assay were performed to explore the interactions between miR-338-3p, FURIN and BDNF. T-RFLP was used to assess the intestinal flora in the stool samples of glioma patients after radiotherapy. We grouped the 106 glioma patients recruited according to the rs4702 polymorphism. The results showed no obvious correlation between rs4702 polymorphism and the expression of miR-338-3p. However, rs4702-A was associated with increased expression of FURIN and BDNF in the serum and PBMC of glioma patients after radiotherapy. Besides, the study found that rs4702-A was remarkably associated with increased enterotype I and decreased enterotype III in the stool of glioma patients after radiotherapy. Rs4702-A was also proved to be closely associated with increased MMSE, role functioning and social functioning at three months after radiotherapy. Furthermore, miR-338-3p repressed the expression of FURIN-G. Compared with G allele, the presence of A allele of rs4702 polymorphism in FURIN could obstruct the suppressive effect of miR-338-3p upon the expression of FURIN and BDNF in intestinal flora. Therefore, the carriers of A allele will be challenged with less risk of radiotherapy-induced cognitive impairment.
Assuntos
Disfunção Cognitiva , Glioma , MicroRNAs , Regiões 3' não Traduzidas/genética , Disfunção Cognitiva/genética , Furina/genética , Glioma/genética , Glioma/metabolismo , Glioma/radioterapia , Humanos , Leucócitos Mononucleares/metabolismo , MicroRNAs/genética , MicroRNAs/metabolismoRESUMO
LncRNA-PTENP1 was reported to promote multiple myeloma cancer stem cell proliferation, and the G allele of rs7853346 polymorphism in lncRNA-PTENP1 was demonstrated to enhance the effect of lncRNA-PTENP1. In this study, we aimed to study the potential effect of lncRNA-PTENP1 and CCR2 mRNA polymorphisms on cognitive impairment in glioma patients. In this study, 279 glioma patients were recruited and grouped according to their genotypes of rs7853346 in PTENP1 and rs1799864 in CCR1. Pathogenic parameters were collected from patients before radiotherapy (month 0) or at month 1 and month 3 after radiotherapy to study the effect of rs7853346 and rs1799864 on cognitive impairment. Sequence analysis, luciferase assay, real-time PCR, and Western blot were performed to study the regulatory relationships between lncRNA-PTENP1, miR-18b, and CCR2. The glioma patient groups exhibited no significant differences concerning basic characteristics. However, the CG&GG/GG genotype alleviated radiotherapy-induced cognitive impairment by exhibiting the highest MMSE among the four groups. On the contrary, parameters including the severity of depression, bladder control, global health status, itchy skin, and weakness of legs all showed no difference among different patient groups at month 0, month 1, and month 3. Also, a long-term positive effect of CG&GG/GG genotype on role functioning and social functioning was also observed after radiotherapy. Compared with patients carrying the CC genotype of rs7853346, the expression of lncRNA-PTENP1 was reduced while the miR-19b level was elevated in patients carrying the CG&GG genotypes of rs7853346. Moreover, the expression of CCR2 mRNA was the highest in the CC/GA&AA group and the lowest in the CG&GG/GG group. Subsequent sequence analysis and luciferase assay indicated that miR-19b could bind to lncRNA-PTENP1 and 3'UTR of CCR2 mRNA, and the knockdown of lncRNA-PTENP1 led to evident up-regulation of miR-19b and down-regulation of CCR2 mRNA/protein in a cellular model, thus verifying the presence of the lncRNA-PTENP1/miR-19b/CCR2 mRNA signaling pathway. In conclusion, by studying the changes in the key parameters of glioma patients who were subjected to radiotherapy, we concluded that the rs7853346 polymorphism in lncRNA-PTENP1 and the rs1799864 polymorphism in CCR2 could independently affect cognitive impairment, while a more significant combined effect on cognitive impairment was exerted in glioma patients via the signaling pathway of PTENP1/miR-19b/CCR2.
Assuntos
Disfunção Cognitiva , Glioma , MicroRNAs , RNA Longo não Codificante , Regiões 3' não Traduzidas , Disfunção Cognitiva/genética , Glioma/genética , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Receptores CCR2/genética , Transdução de Sinais/genéticaRESUMO
The new polycyclic polyprenylated acylphloroglucinols, hyperforcinols A-J (1-10), were isolated from the fruits of Hypericum forrestii, together with 30 biogenetic congeners of known structures. The structures of hyperforcinols A-J were determined by HRESIMS and 1D/2D NMR spectroscopic analysis, and their absolute configurations were determined by a combination of the electronic circular dichroism (ECD) exciton chirality method, ECD calculations, and X-ray diffraction analysis. A selection of 25 isolates, possessing seven types of carbon skeletons, were assessed for their in vitro effects against nonalcoholic steatohepatitis (NASH) using a free fatty acid-induced L02 cell model. Compounds 20 and 40 significantly decreased intracellular lipid accumulation. QRT-PCR analyses revealed that compounds 20 and 40 regulate the expression of lipid metabolism-related genes, including CD36, FASN, PPARα, and ACOX1.
Assuntos
Hypericum/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Floroglucinol/farmacologia , Linhagem Celular , China , Frutas/química , Humanos , Estrutura Molecular , Floroglucinol/isolamento & purificação , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia , PrenilaçãoRESUMO
It is now commonly known that exposure to polybrominated diphenyl ethers (PBDEs) may cause neurotoxicity and cognitive deficits in children as well as adults, but the underlying mechanisms are still not clear. In the present study, we aimed to elucidate the potential underlying mechanism of 2,2',4,4'-tetrabromodiphenyl ether (BDE-47)-induced neurotoxicity and cognitive impairment. Our results showed that BDE-47-treated mice exhibited impaired cognition and robust upregulation of nuclear TDP-43 in the hippocampus. Hippocampus-specific TDP-43 knockdown attenuated hippocampal apoptosis, restored synaptic protein levels and thus improved cognitive dysfunction in BDE-47-treated mice. Furthermore, our data demonstrated that NLRP3 inflammasome activation played a distinct role in the upregulation of nuclear TDP-43 by downregulating Parkin in the hippocampus of BDE-47-treated mice. Knocking down NLRP3 in the hippocampus or inhibiting caspase 1 activity in BDE-47-treated mice effectively increased Parkin expression in the hippocampus, which decreased the levels of nuclear TDP-43 and ultimately abrogated TDP-43-induced neurotoxic effects. Taken together, our data indicate that TDP-43 upregulation mediated by NLRP3 inflammasome activation via Parkin downregulation in the hippocampus induces cognitive decline in BDE-47-treated mice, and suggest that inhibition of NLRP3 or TDP-43 may be a potential strategy for the prevention or treatment of cognitive impairment in BDE-47-induced neurotoxicity and brain diseases.
Assuntos
Disfunção Cognitiva/metabolismo , Proteínas de Ligação a DNA/efeitos dos fármacos , Proteínas de Ligação a DNA/metabolismo , Animais , Apoptose/efeitos dos fármacos , Disfunção Cognitiva/induzido quimicamente , Proteínas de Ligação a DNA/genética , Éteres Difenil Halogenados/farmacologia , Hipocampo/efeitos dos fármacos , Inflamassomos/metabolismo , Inflamassomos/fisiologia , Camundongos , Camundongos Endogâmicos C57BL , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/fisiologia , Síndromes Neurotóxicas/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ativação Transcricional , Regulação para CimaRESUMO
We previously demonstrated that the typical mitochondrial uncoupler carbonyl cyanide m-chlorophenylhydrazone (CCCP) inhibited artery constriction, but CCCP was used only as a pharmacological tool. Niclosamide is an anthelmintic drug approved by FDA. Niclosamide ethanolamine (NEN) is a salt form of niclosamide and has been demonstrated to uncouple mitochondrial oxidative phosphorylation. The aim of the present study was to elucidate the vasoactivity of NEN and the potential mechanisms. Isometric tension of rat mesenteric artery and thoracic aorta was recorded by using multi-wire myograph system. The protein levels were measured by using western blot techniques. Niclosamide ethanolamine (NEN) treatment relaxed phenylephrine (PE)- and high K+ (KPSS)-induced constriction, and pre-treatment with NEN inhibited PE- and KPSS-induced constriction of rat mesenteric arteries. In rat thoracic aorta, NEN also showed antagonism against PE- and KPSS-induced constriction. NEN induced increase of cellular ADP/ATP ratio in vascular smooth muscle cells (A10) and activated AMP-activated protein kinase (AMPK) in A10 cells and rat thoracic aorta. NEN-induced aorta relaxation was attenuated in AMPKα1 knockout (-/-) mice. SERCA inhibitors cyclopiazonic acid and thapsigargin, but not KATP channel blockers glibenclamide and 5-hydroxydecanoic acid, attenuated NEN-induced vasorelaxation in rat mesenteric arteries. NEN treatment increased cytosolic [Ca2+]i and depolarized mitochondrial membrane potential in vascular smooth muscle cells (A10). Niclosamide in non-salt form showed the similar vasoactivity as NEN in rat mesenteric arteries. Niclosamide ethanolamine inhibits artery constriction, indicating that it would be promising to be developed as an anti-hypertensive drug or it would induce vasodilation-related side effects when absorbed in vivo.
Assuntos
Aorta Torácica/efeitos dos fármacos , Etanolamina/farmacologia , Artérias Mesentéricas/efeitos dos fármacos , Niclosamida/farmacologia , Vasoconstrição/efeitos dos fármacos , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Anti-Hipertensivos/farmacologia , Aorta/efeitos dos fármacos , Aorta/metabolismo , Aorta Torácica/metabolismo , Canais KATP/antagonistas & inibidores , Masculino , Artérias Mesentéricas/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Músculo Liso Vascular/efeitos dos fármacos , Músculo Liso Vascular/metabolismo , Miócitos de Músculo Liso/efeitos dos fármacos , Miócitos de Músculo Liso/metabolismo , Fenilefrina/farmacologia , Ratos , Ratos Sprague-Dawley , Doenças Vasculares/tratamento farmacológico , Doenças Vasculares/metabolismo , Vasodilatação/efeitos dos fármacos , Vasodilatadores/farmacologiaRESUMO
This study aimed to evaluate the relationship of serum levels of vascular endothelial growth factor (VEGF) and transforming growth factor-ß1 (TGF-ß1) with radiosensitivity of elderly patients with unresectable non-small cell lung cancer (NSCLC) receiving three-dimensional conformal radiation therapy (3D-CRT). Fifty-eight elderly patients with unresectable NSCLC and 40 healthy controls were enrolled in this study. Serum levels of VEGF and TGF-ß1 were detected by the enzyme-linked immunosorbent assay (ELISA) method before and after 3D-CRT. Clinical performances of serum VEGF and TGF-ß1 levels in predicting radiosensitivity of NSCLC patients with 3D-CRT were evaluated. Serum VEGF and TGF-ß1 levels of NSCLC patients were higher than those of health controls (all p < 0.05). After 3D-CRT treatment, 41 patients achieved effective clinical response (complete response (CR) + partial response (PR)) and 17 patients were ineffective clinical response (stable disease (SD) + progressive disease (PD)). There was no significant difference in the VEGF and TGF-ß1 levels between the effective and ineffective groups before 3D-CRT (all p > 0.05). Serum levels of VEGF and TGF-ß1 after 3D-CRT in the effective group were lower compared with the levels before 3D-CRT treatment (p < 0.001 and 0.027, respectively). However, no significant differences in serum VEGF and TGF-ß1 levels between before and after 3D-CRT in the ineffective group were observed (p = 0.196 and 0.517, respectively). We observed significant differences in serum VEGF and TGF-ß1 levels between the effective and ineffective groups after 3D-CRT (p < 0.001 and 0.013, respectively). Sensitivity and specificity of VEGF combined with TGF-ß1 in predicting radiosensitivity of NSCLC patients with 3D-CRT were 87.8 and 94.1%, respectively. In conclusion, our results indicate that serum VEGF and TGF-ß1 levels may accurately predict radiosensitivity of elderly patients with unresectable NSCLC receiving 3D-CRT.
Assuntos
Carcinoma Pulmonar de Células não Pequenas/radioterapia , Neoplasias Pulmonares/radioterapia , Tolerância a Radiação , Radioterapia Conformacional/métodos , Fator de Crescimento Transformador beta1/sangue , Fator A de Crescimento do Endotélio Vascular/sangue , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/sangue , Feminino , Humanos , Neoplasias Pulmonares/sangue , Masculino , Pessoa de Meia-IdadeRESUMO
Our previous findings suggest that mitochondrial dysfunction is the mechanism underlying cognitive deficits induced by domoic acid (DA). Ursolic acid (UA), a natural triterpenoid compound, possesses many important biological functions. Evidence shows that UA can activate PI3K/Akt signaling and suppress Forkhead box protein O1 (FoxO1) activity. FoxO1 is an important regulator of mitochondrial function. Here we investigate whether FoxO1 is involved in the oxidative stress-induced mitochondrial dysfunction in DA-treated mice and whether UA inhibits DA-induced mitochondrial dysfunction and cognitive deficits through regulating the PI3K/Akt and FoxO1 signaling pathways. Our results showed that FoxO1 knockdown reversed the mitochondrial abnormalities and cognitive deficits induced by DA in mice through decreasing HO-1 expression. Mechanistically, FoxO1 activation was associated with oxidative stress-induced JNK activation and decrease of Akt phosphorylation. Moreover, UA attenuated the mitochondrial dysfunction and cognitive deficits through promoting Akt phosphorylation and FoxO1 nuclear exclusion in the hippocampus of DA-treated mice. LY294002, an inhibitor of PI3K/Akt signaling, significantly decreased Akt phosphorylation in the hippocampus of DA/UA mice, which weakened UA actions. These results suggest that UA could be recommended as a possible candidate for the prevention and therapy of cognitive deficits in excitotoxic brain disorders.
Assuntos
Transtornos Cognitivos/induzido quimicamente , Transtornos Cognitivos/prevenção & controle , Inibidores de Ciclo-Oxigenase/uso terapêutico , Ácido Caínico/análogos & derivados , Fármacos Neuromusculares Despolarizantes/efeitos adversos , Fármacos Neuromusculares Despolarizantes/toxicidade , Triterpenos/uso terapêutico , Animais , Animais Geneticamente Modificados , Transtornos Cognitivos/psicologia , Dependovirus , Imunofluorescência , Proteína Forkhead Box O1 , Fatores de Transcrição Forkhead/metabolismo , Vetores Genéticos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Ácido Caínico/antagonistas & inibidores , Ácido Caínico/toxicidade , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Doenças Mitocondriais/induzido quimicamente , Doenças Mitocondriais/prevenção & controle , Proteína Oncogênica v-akt/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Fosfatidilinositol 3-Quinases/metabolismo , Desempenho Psicomotor/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Ácido UrsólicoRESUMO
Nonylphenol (NP) is an ultimate degradation product of nonylphenol polyethoxylates (NPE) that is primarily used in cleaning and industrial processes. Its widespread use has led to the wide existence of NP in various environmental matrices, such as water, sediment, air and soil. NP can be decreased by biodegradation through the action of microorganisms under aerobic or anaerobic conditions. Half-lives of biodegradation ranged from a few days to almost one hundred days. The degradation rate for NP was influenced by temperature, pH and additions of yeast extracts, surfactants, aluminum sulfate, acetate, pyruvate, lactate, manganese dioxide, ferric chloride, sodium chloride, hydrogen peroxide, heavy metals, and phthalic acid esters. Although NP is present at low concentrations in the environment, as an endocrine disruptor the risks of long-term exposure to low concentrations remain largely unknown. This paper reviews the occurrence of NP in the environment and its aerobic and anaerobic biodegradation in natural environments and sewage treatment plants, which is essential for assessing the potential risk associated with low level exposure to NP and other endocrine disruptors.
Assuntos
Disruptores Endócrinos/metabolismo , Fenóis/metabolismo , Poluentes Químicos da Água/metabolismo , Poluentes Atmosféricos/química , Poluentes Atmosféricos/metabolismo , Biodegradação Ambiental , Disruptores Endócrinos/química , Metais Pesados/química , Fenóis/química , Microbiologia do Solo , Poluentes do Solo/metabolismo , Tensoativos/química , Poluentes Químicos da Água/químicaRESUMO
Objective: To retrospectively analyze the clinical characters and prognosis of the patients with Esophageal Squamous Cell Carcinomas as First Primary Malignancy (ESCCFPM), which will help us better understand the relationship between Esophageal Squamous Cell Carcinoma (ESCC) and other cancers, and to provide appropriate research evidence for the clinical diagnosis and treatment. Methods: The clinicopathological and follow-up data of 540 Patients with ESCCFPM between January 1, 2004 and December 31, 2016 were collected from the Surveillance, Epidemiology and End Results (SEER) database of National Cancer Institute. The Kaplan-Meier method was used to determine Overall Survival (OS) curves of ESCC patients, and the Log-Rank test was used to estimate differences in survival. The Cox proportional hazards models were adopted for the prognosis analyses. Results: Regarding the number of multiple primary malignancies (MPMs), 491 had two malignancies, 42 had three malignancies and 7 had four malignancies. ESCCFPM is more common among males. The high incidence age is between 61 and 80 years old. Tumors of the respiratory system (36.9%), were the most common MPMs followed by digestive system (35.2%) and reproductive system (8.9%). The 1-year, 3-year, 5-year OS rates for patients with ESCCFPM were 76.9%, 50.4% and 38.9%, respectively. The age of the ESCC diagnosed, T stage, time of occurrence, carcinoma number, lymph node dissection, surgery, radiotherapy and chemotherapy were the prognostic factor of overall survival for ESCCFPM patients. Age, race, T stage, time of occurrence surgery and radiotherapy were independent prognostic factors for the whole cohort by multivariate survival analysis. Conclusion: ESCCFPM,mainly two-lesion cancer, is most commonly found in respiratory system and digestive systems. Enhanced follow-up of respiratory and digestive tumors in ESCCFPM patients aged 61-80 may help identify multiple primary malignancies. Surgery, radiotherapy and chemotherapy may improve overall survival for ESCCFPM patients.
Assuntos
Carcinoma de Células Escamosas , Neoplasias Esofágicas , Carcinoma de Células Escamosas do Esôfago , Idoso , Idoso de 80 Anos ou mais , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/patologia , Humanos , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos RetrospectivosRESUMO
Non-alcoholic steatohepatitis (NASH) is the progressive stage of non-alcoholic fatty liver disease that may ultimately lead to cirrhosis and liver cancer, and there are few therapeutic options for its treatment. Physalin B (PB), a withanolide isolated from Physalis species (Solanaceae), exhibits a broad spectrum of biological activities, however, the potential role of PB in NASH has not been evaluated. The present study investigated the protective effects of PB against NASH and further elucidated the mechanisms of PB in hepatic autophagy and oxidative stress in vitro and in vivo. We conducted a series of experiments using methionine-choline deficient (MCD) diet induced NASH mice and cultured L02 cells. Serum markers of liver injury, morphology, and the histology of liver tissues were investigated. Western blot assays and quantitative real-time PCR were used to investigate the hepatoprotective effect of PB. PB significantly ameliorated hepatic injury, including hepatic index, transaminase activities, histology, and inflammation in MCD-induced mice. Moreover, PB markedly increased the expression of P62 and the ratio of LC3â ¡/â in vitro and in vivo. Furthermore, PB promoted the interaction between endogenous KEAP1 and P62, reduced the interaction between KEAP1 and NRF2, activated the nuclear translocation of NRF2 and NRF2 target gene expression, and ultimately attenuated oxidative stress. In addition, knockdown of P62 blocked PB-mediated activation of NRF2 in L02 cells. These results clearly indicated that PB ameliorated NASH by stimulating autophagy and P62-KEAP1-NRF2 antioxidative signaling, suggesting that PB is expected to become a novel therapeutic drug for NASH.
Assuntos
Hepatopatia Gordurosa não Alcoólica , Animais , Autofagia , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Fígado/metabolismo , Metionina/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/metabolismo , Estresse Oxidativo , SecoesteroidesRESUMO
Nonylphenol (NP) is a degradation product of nonylphenol polyethoxylates, which are widely used in the production of industrial and consumer surfactants. The aim of the present study was to evaluate the effect of NP on the antioxidant capacity and cognitive ability of mice. NP was given orally by gavages at doses of 0, 50, 100, and 200 mg kg(-1) d(-1) for 90 days. The results showed that NP significantly decreased the activity of superoxide dismutases (SOD), catalase (CAT), glutathione peroxidase (GPx), and glutathione reductase (GR) and at the same time increased malondialdehyde (MDA) levels in mice brains. Exploration, memory function and ability to learn a novel task were significantly decreased in NP fed mice. These results indicate that chronic high dose of NP exposure has the potential to generate oxidative stress and induce the cognitive impairment in male mice.
Assuntos
Comportamento Animal/efeitos dos fármacos , Poluentes Ambientais/toxicidade , Aprendizagem em Labirinto/efeitos dos fármacos , Estresse Oxidativo , Fenóis/toxicidade , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Peroxidação de Lipídeos/efeitos dos fármacos , Masculino , Camundongos Endogâmicos , Testes de ToxicidadeRESUMO
OBJECTIVE: To determine the anti-inflammatory functions of different cysteine mutants of apolipoprotein A-I recombinant HDLs. METHODS: The recombinant HDLs (named rHDL52, rHDL107, rHDL173, rHDLwt) were reconstituted by mixing wild types or their mutants with dipalmitoyl phosphatidylcholine. And the in vivo effects on lipopolysaccharide (LPS)-induced endotoxemia were examined in mice. The plasma levels of plasma tumor necrosis factor (TNF)-alpha, interleukin (IL)-1beta and IL-6 in by ELISA were tested. And we also set up two control groups: LPS and saline. RESULTS: The rHDL52 mice had a significant decrease of plasma TNF-alpha and IL-1beta and the protection of lung against acute injury. 24 h post-injection as compared with rHDLwt group [TNF-alpha: (135.28 +/- 12.84) pg/ml, IL-1beta: (82.00 +/- 8.19) pg/ml], the rHDL52 mice exhibited a higher capability of lowering the plasma levels of TNF-alpha and IL-1beta [(39.66 +/- 2.44) pg/ml, (66.83 +/- 6.24) pg/ml, both P < 0.05]. And, as indicated by histological sections of lung tissue, the rHDL52 mice could also lower the infiltration of inflammatory cells in lung. CONCLUSION: rHDL52 has a higher anti-inflammation capability than wild type rHDLwt.
Assuntos
Anti-Inflamatórios/farmacologia , Apolipoproteína A-I/farmacologia , Cisteína/farmacologia , Endotoxemia/sangue , Animais , Apolipoproteína A-I/genética , Cisteína/genética , Endotoxemia/patologia , Interleucina-1beta/sangue , Lipopolissacarídeos , Pulmão/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Monossacarídeos , Mutação , Oligopeptídeos , Proteínas Recombinantes/genética , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/sangueRESUMO
BACKGROUND: The World Health Organization End TB Strategy meant that compared with 2015 baseline, the reduction in pulmonary tuberculosis (PTB) incidence should be 20 and 50% in 2020 and 2025, respectively. The case number of PTB in China accounted for 9% of the global total in 2018, which ranked the second high in the world. From 2007 to 2019, 854 672 active PTB cases were registered and treated in Henan Province, China. This study was to assess whether the WHO milestones could be achieved in Henan Province. METHODS: The active PTB numbers in Henan Province from 2007 to 2019, registered in Chinese Tuberculosis Information Management System were analyzed to predict the active PTB registration rates in 2020 and 2025, which is conductive to early response measures to ensure the achievement of the WHO milestones. The time series model was created by monthly active PTB registration rates from 2007 to 2016, and the optimal model was verified by data from 2017 to 2019. The Ljung-Box Q statistic was used to evaluate the model. The statistically significant level is α = 0.05. Monthly active PTB registration rates and 95% confidence interval (CI) from 2020 to 2025 were predicted. RESULTS: High active PTB registration rates in March, April, May and June showed the seasonal variations. The exponential smoothing winter's multiplication model was selected as the best-fitting model. The predicted values were approximately consistent with the observed ones from 2017 to 2019. The annual active PTB registration rates were predicted as 49.1 (95% CI: 36.2-62.0) per 100 000 population and 34.4 (95% CI: 18.6-50.2) per 100 000 population in 2020 and 2025, respectively. Compared with the active PTB registration rate in 2015, the reduction will reach 23.7% (95% CI, 3.2-44.1%) and 46.8% (95% CI, 21.4-72.1%) in 2020 and 2025, respectively. CONCLUSIONS: The high active PTB registration rates in spring and early summer indicate that high risk of tuberculosis infection in late autumn and winter in Henan Province. Without regard to the CI, the first milestone of WHO End TB Strategy in 2020 will be achieved. However, the second milestone in 2025 will not be easily achieved unless there are early response measures in Henan Province, China.
Assuntos
Sistema de Registros , Tuberculose Pulmonar/epidemiologia , China/epidemiologia , Feminino , Humanos , Incidência , Masculino , Estações do Ano , Análise Espaço-Temporal , Organização Mundial da SaúdeRESUMO
OBJECTIVE: To observe the clinical effects of acupuncture for allergic rhinitis. METHODS: The body acupuncture, auricular seed-embedding and microwave irradiation were adopted for treatment of allergic rhinitis due to various causative factors, such as cold and insufficiency of the lung-qi weakening the body resistance, insufficiency of the spleen-qi with lucid yang failing to rise, insufficiency of the kidney-yang failing to warm the body surface, and the heat accumulated in the lung channels giving invading the nose. RESULTS: After treatment, the symptoms and signs disappeared in all illustrative cases, with no recurrence found after a one-year follow-up. CONCLUSION: Acupuncture may help to improve the blood theology indexes with an increased volume of blood flow, and regulate the immunological function of the human body, thus giving therapeutic effects for allergic rhinitis.
Assuntos
Terapia por Acupuntura/métodos , Rinite Alérgica Perene/terapia , Rinite Alérgica Sazonal/terapia , Pontos de Acupuntura , Terapia por Acupuntura/instrumentação , Adulto , Feminino , Humanos , Guias de Prática Clínica como Assunto , Qi , Temperatura , Resultado do TratamentoRESUMO
OBJECTIVE: To study the insular development of small for gestational age (SGA) infants. METHODS: The insular area and circle were measured by cerebral ultrasonography in 92 SGA infants. The results were compared with those from 109 appropriate for gestational age (AGA) infants. RESULTS: The insular area and circle were positively correlated with the birth weight and gestational age in SGA infants. The insular area in SGA infants with a gestational age of either >37 weeks (451 +/- 92 mm2 vs 516 +/- 116 mm2; p<0.01) or < or = 34 weeks (248 +/- 78 mm2 vs 314 +/- 80 mm2; p<0.01) was significantly less than that in the AGA infants. The insular circle in SGA infants with a gestational age of >37 weeks was also significantly less than that in the AGA infants (92 +/- 11 mm vs 97 +/- 11 mm; p<0.05). CONCLUSIONS: The insular development of SGA infants seems to be immature. The insular development may be assessed based on the insular area and circle measured by cerebral ultrasonography.
Assuntos
Córtex Cerebral/embriologia , Recém-Nascido Pequeno para a Idade Gestacional , Peso ao Nascer , Ecoencefalografia , Feminino , Idade Gestacional , Humanos , Recém-Nascido , MasculinoRESUMO
Antibiotics are one of the emerging contaminants in water, which have a great impact on ecosystems and human health. It has been challenging to simultaneously realize low-cost, rapid, highly sensitive and selective detection of antibiotics with conventional methods. Here, we report luminescent chemosensors for detecting antibiotics in water, based on metal-organic framework (MOF), i.e., zeolitic imidazolate framework-8 (ZIF-8), loaded with rhodamine B (RhB) and fluorescein disodium salt (FSS) dyes. Compared with ZIF-8, the fluorescence signals of RhB@ZIF-8 and FSS@ZIF-8 were significantly improved and presented ultrahigh sensitivity to nitrofurans (NFAs) and tetracyclines (TCs) with fluorescence quenching and fluorescence enhancement in water, respectively. The unique structures and properties of RhB@ZIF-8 and FSS@ZIF-8 lead to outstanding sensitivities in antibiotic detection. For instance, the RhB@ZIF-8 sensor shows the lower limit of detection (LOD) of 0.26⯵M to nitrofurantoin (NFT), 0.47⯵M to nitrofurazone (NFZ), 0.11⯵M to tetracycline (TC), and 0.14⯵M to oxytetracycline (OTC); while the FSS@ZIF-8 sensor shows the LOD of 0.31⯵M to NFT, 0.35⯵M to NFZ, 0.17⯵M to TC, and 0.16⯵M to OTC. In addition, NFT and TC were also successfully detected by FSS@ZIF-8 in water from real water environment. The results indicate that dye@MOF-based luminescent composites are favorable for antibiotic detection, presenting great potentials in water quality monitoring.
RESUMO
The ubiquitously expressed multifunctional protein, CUEDC2 (CUE domain-containing 2), is involved in many physiological and pathological processes, including the cell cycle regulation and inflammation. Although it is known that CUEDC2 is expressed disparately in breast cancer, ovarian carcinoma, hepatocellular carcinoma, cholangiocarcinoma, glioma, lung adenocarcinoma, colon cancers, and is involved in the Warburg's effect, its role in oncogenesis remains to be further explored. In this review, we examine the expression of CUEDC2 in various tumors, and discuss several fundamental signaling pathways that are impacted by CUEDC2.
Assuntos
Carcinogênese/metabolismo , Proteínas de Transporte/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Adaptadoras de Transdução de Sinal , Adenocarcinoma/metabolismo , Animais , Neoplasias Encefálicas/metabolismo , Neoplasias da Mama/metabolismo , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , Colangiocarcinoma/metabolismo , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Glioma/metabolismo , Humanos , Inflamação , Neoplasias Hepáticas/metabolismo , Neoplasias Pulmonares/metabolismo , Macrófagos/patologia , Masculino , Camundongos , Mitose , NF-kappa B/metabolismo , Neoplasias Ovarianas/metabolismoRESUMO
The first examples of type B polycyclic polyprenylated acylphloroglucinols with a bicyclo[5.3.1]hendecane core, hyperberins A (1) and B (2), were isolated from Hypericum beanii, together with three biosynthetic congeners. Their structures were established by a combination of NMR, electric circular dichroism (ECD), and X-ray diffraction analyses. These isolates indicated divergent cationic cyclization as key steps in the biosynthesis of PPAPs with diverse architectures. Compounds 1 and 2 were moderately cytotoxic and exhibited significant anti-inflammatory activities.
RESUMO
Chinese horseshoe crabs (Tachypleus tridentatus), ancient marine arthropods dating back to the mid-Palaeozoic Era, have provided valuable resources for the detection of bacterial or fungal contamination. However, excessive exploitation for the amoebocyte lysate of Tachypleus has dramatically decreased the population of the Chinese horseshoe crabs. Thus, we present sequencing, assembly and annotation of T. tridentatus, with the hope of understanding the genomic feature of the living fossil and assisting scientists with the protection of this endangered species. The final genome contained a total size of 1.943 Gb, covering 90.23% of the estimated genome size. The transcriptome of three larval stages was constructed to investigate the candidate gene involved in the larval development and validate annotation. The completeness of the genome and gene models was estimated by BUSCO, reaching 96.2% and 95.4%, respectively. The synonymous substitution distribution of paralogues revealed that T. tridentatus had undergone two rounds of whole-genome duplication. All genomic and transcriptome data have been deposited in public databases, ready to be used by researchers working on horseshoe crabs.