RESUMO
Twenty-nine sesquiterpenoids, including pseudoguaiane-type (1-11), eudesmane-type (12-23), and carabrane-type (24-29), have been identified from the plant Carpesium abrotanoides. Of them, compounds 1-4, 12-15, and 24-27, namely carpabrotins A-L, are twelve previously undescribed ones. Compound 3 possessed a pseudoguaiane backbone with a rearrangement modification at C-11, C-12 and C-13, while compound 4 suffered a carbon bond break between the C-4 and C-5 to form a rare 4,5-seco-pseudoguaiane lactone. Compounds 1-3, 5, 13-16 and 25-27 exhibited anti-inflammatory activity by inhibiting NO production in LPS-induced RAW264.7 macrophages with IC50 values less than 40 µM, while compounds 1, 2, 5, 13, 14, 16, and 25-27 showed significant inhibitory activity comparable to that of dexamethasone. The anti-atopic dermatitis (AD) effects of compounds 5 and 16 were tested according to 2,4-dinitrochlorobenzene (DNCB)-induced AD-like skin lesions in KM mice, and the results revealed that the major products 5 and 16 improved the histological features of AD-like skin lesions and mast cell infiltration in mice. This study suggested that sesquiterpenoids in C. abrotanoides should play a key role in its anti-inflammatory use.
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Asteraceae , Óxido Nítrico , Sesquiterpenos , Animais , Camundongos , Sesquiterpenos/farmacologia , Sesquiterpenos/química , Sesquiterpenos/isolamento & purificação , Asteraceae/química , Células RAW 264.7 , Óxido Nítrico/antagonistas & inibidores , Óxido Nítrico/biossíntese , Óxido Nítrico/metabolismo , Estrutura Molecular , Relação Estrutura-Atividade , Relação Dose-Resposta a Droga , Lipopolissacarídeos/antagonistas & inibidores , Lipopolissacarídeos/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Macrófagos/efeitos dos fármacos , MasculinoRESUMO
Multiwalled carbon nanotubes (MWCNTs) have numerous applications in the field of carbon nanomaterials. However, the associated toxicity concerns have increased significantly because of their widespread use. The inhalation of MWCNTs can lead to nanoparticle deposition in the lung tissue, causing inflammation and health risks. In this study, celastrol, a natural plant medicine with potent anti-inflammatory properties, effectively reduced the number of inflammatory cells, including white blood cells, neutrophils, and lymphocytes, and levels of inflammatory cytokines, such as IL-1ß, IL-6, and TNF-α, in mice lungs exposed to MWCNTs. Moreover, celastrol inhibited the activation of the NF-κB-signaling pathway. This study confirmed these findings by demonstrating comparable reductions in inflammation upon exposure to MWCNTs in mice with the deletion of NF-κB (P50-/-). These results indicate the utility of celastrol as a promising pharmacological agent for preventing MWCNT-induced lung tissue inflammation.
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Nanotubos de Carbono , Triterpenos Pentacíclicos , Pneumonia , Transdução de Sinais , Triterpenos , Animais , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Líquido da Lavagem Broncoalveolar/citologia , Líquido da Lavagem Broncoalveolar/química , Citocinas/metabolismo , Pulmão/efeitos dos fármacos , Pulmão/patologia , Pulmão/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Nanotubos de Carbono/toxicidade , NF-kappa B/metabolismo , Triterpenos Pentacíclicos/farmacologia , Pneumonia/induzido quimicamente , Pneumonia/tratamento farmacológico , Pneumonia/prevenção & controle , Pneumonia/metabolismo , Transdução de Sinais/efeitos dos fármacos , Triterpenos/farmacologiaRESUMO
OBJECTIVE: This study aims to assess the clinical effectiveness of combining mindfulness-based stress reduction (MBSR) with exercise intervention in improving anxiety, depression, sleep quality and mood regulation in patients with non-small cell lung cancer (NSCLC). METHODS: A total of 60 patients with NSCLC who had not received surgical treatment were selected using convenience sampling and divided into an intervention group and control group, with 30 patients in each group. The control group received conventional psychological nursing care, whereas the intervention group received a combination of MBwSR and exercise therapy. Before the intervention, a questionnaire was completed to collect the basic data of the two groups. Further questionnaires were administered at 6 and 8 weeks after treatment to assess anxiety, depression, sleep quality and other items included in the five-item Brief Symptom Rating Scale (BSRS-5). RESULTS: No significant differences between the intervention and control groups were identified in terms of personal and clinical characteristics (p > 0.05). No significant differences were determined in the BSRS-5, Self-Rating Anxiety Scale (SAS), Self-Rating Depression Scale (SDS) or Pittsburgh Sleep Quality Index (PSQI) scores between the intervention and control groups before the intervention. However, 6 and 8 weeks after the intervention, scores were significantly lower in both groups (p < 0.001). Significant differences in the BSRS-5, SAS, SDS and PSQI scores were identified between the two groups at different time points (p < 0.001). CONCLUSION: The combination of MBSR and exercise intervention demonstrated improvements in anxiety, depression, sleep quality and BSRS-5 scores in patients with NSCLC.
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Carcinoma Pulmonar de Células não Pequenas , Terapia por Exercício , Neoplasias Pulmonares , Atenção Plena , Estresse Psicológico , Humanos , Atenção Plena/métodos , Feminino , Masculino , Carcinoma Pulmonar de Células não Pequenas/psicologia , Carcinoma Pulmonar de Células não Pequenas/terapia , Pessoa de Meia-Idade , Neoplasias Pulmonares/psicologia , Neoplasias Pulmonares/terapia , Terapia por Exercício/métodos , Terapia por Exercício/psicologia , Estresse Psicológico/terapia , Estresse Psicológico/psicologia , Resultado do Tratamento , Idoso , Inquéritos e Questionários , Adulto , Qualidade do Sono , Terapia Combinada , Bem-Estar PsicológicoRESUMO
BACKGROUND: The prognostic role of either forkhead box A1 (FOXA1) or anterior gradient 2 (AGR2) in breast cancer has been found separately. Considering that there were interplays between them depending on ER status, we aimed to assess the statistical interaction between AGR2 and FOXA1 on breast cancer prognosis and examine the prognostic role of the combination of them by ER status. METHODS: AGR2 and FOXA1 expression in tumor tissues were evaluated with tissue microarrays by immunohistochemistry in 915 breast cancer patients with follow up data. The expression levels of these two markers were treated as binary variables, and many different cutoff values were tried for each marker. Survival and Cox proportional hazard analyses were used to evaluate the relationship between AGR2, FOXA1 and prognosis, and the statistical interaction between them on the prognosis was assessed on multiplicative scale. RESULTS: Statistical interaction between AGR2 and FOXA1 on the PFS was significant with all the cutoff points in ER-positive breast cancer patients but not ER-negative ones. Among ER-positive patients, the poor prognostic role of the high level of FOXA1 was significant only in patients with the low level of AGR2, and vice versa. When AGR2 and FOXA1 were considered together, patients with low levels of both markers had significantly longer PFS compared with all other groups. CONCLUSIONS: There was a statistical interaction between AGR2 and FOXA1 on the prognosis of ER-positive breast cancer. The combination of AGR2 and FOXA1 was a more useful marker for the prognosis of ER-positive breast cancer patients.
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Neoplasias da Mama , Humanos , Feminino , Prognóstico , Mama/patologia , Imuno-Histoquímica , Fator 3-alfa Nuclear de Hepatócito/metabolismo , Biomarcadores Tumorais/metabolismo , Mucoproteínas , Proteínas OncogênicasRESUMO
Non-healing diabetic wounds (DW) are a serious clinical problem that remained poorly understood. We recently found that topical application of growth differentiation factor 11 (GDF11) accelerated skin wound healing in both Type 1 DM (T1DM) and genetically engineered Type 2 diabetic db/db (T2DM) mice. In the present study, we elucidated the cellular and molecular mechanisms underlying the action of GDF11 on healing of small skin wound. Single round-shape full-thickness wound of 5-mm diameter with muscle and bone exposed was made on mouse dorsum using a sterile punch biopsy 7 days following the onset of DM. Recombinant human GDF11 (rGDF11, 50 ng/mL, 10 µL) was topically applied onto the wound area twice a day until epidermal closure (maximum 14 days). Digital images of wound were obtained once a day from D0 to D14 post-wounding. We showed that topical application of GDF11 accelerated the healing of full-thickness skin wounds in both type 1 and type 2 diabetic mice, even after GDF8 (a muscle growth factor) had been silenced. At the cellular level, GDF11 significantly facilitated neovascularization to enhance regeneration of skin tissues by stimulating mobilization, migration and homing of endothelial progenitor cells (EPCs) to the wounded area. At the molecular level, GDF11 greatly increased HIF-1É expression to enhance the activities of VEGF and SDF-1É, thereby neovascularization. We found that endogenous GDF11 level was robustly decreased in skin tissue of diabetic wounds. The specific antibody against GDF11 or silence of GDF11 by siRNA in healthy mice mimicked the non-healing property of diabetic wound. Thus, we demonstrate that GDF11 promotes diabetic wound healing via stimulating endothelial progenitor cells mobilization and neovascularization mediated by HIF-1É-VEGF/SDF-1É pathway. Our results support the potential of GDF11 as a therapeutic agent for non-healing DW.
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Diabetes Mellitus Experimental , Células Progenitoras Endoteliais , Fatores de Diferenciação de Crescimento , Cicatrização , Animais , Humanos , Camundongos , Proteínas Morfogenéticas Ósseas/metabolismo , Quimiocina CXCL12/efeitos dos fármacos , Quimiocina CXCL12/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Células Progenitoras Endoteliais/metabolismo , Células Progenitoras Endoteliais/patologia , Fatores de Diferenciação de Crescimento/uso terapêutico , Fatores de Diferenciação de Crescimento/metabolismo , Neovascularização Fisiológica , Fator A de Crescimento do Endotélio Vascular/efeitos dos fármacos , Fator A de Crescimento do Endotélio Vascular/metabolismo , Cicatrização/efeitos dos fármacos , Proteínas Recombinantes/metabolismo , Proteínas Recombinantes/uso terapêutico , Subunidade alfa do Fator 1 Induzível por Hipóxia/efeitos dos fármacos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismoRESUMO
BACKGROUND: Results of previous studies about the prognostic roles of histone H4 lysine 16 acetylation (H4K16ac) and histone H4 lysine 20 trimethylation (H4K20me3) in breast cancer were inconsistent. Cellular experiments revealed the interplays between H4K16ac and H4K20me3, but no population study explored the interaction between them on the prognosis. METHODS: H4K16ac and H4K20me3 levels in tumors were evaluated by immunohistochemistry for 958 breast cancer patients. Hazard ratios for overall survival (OS) and progression-free survival (PFS) were estimated using Cox regression models. Interaction was assessed on multiplicative scale. Concordance index (C-index) was calculated to verify the predictive performance. RESULTS: The prognostic roles of the low level of H4K16ac or H4K20me3 were significant only in patients with the low level of another marker and their interactions were significant. Moreover, compared with joint high levels of both them, only the combined low levels of both them was associated with a poor prognosis but not the low level of single one. The C-index of the clinicopathological model combined the joint expression of H4K16ac and H4K20me3 [0.739 for OS; 0.672 for PFS] was significantly larger than that of the single clinicopathological model [0.699 for OS, P < 0.001; 0.642 for PFS, P = 0.003] or the model combined with the single H4K16ac [0.712 for OS, P < 0.001; 0.646 for PFS, P < 0.001] or H4K20me3 [0.724 for OS, P = 0.031; 0.662 for PFS, P = 0.006]. CONCLUSIONS: There was an interaction between H4K16ac and H4K20me3 on the prognosis of breast cancer and the combination of them was a superior prognostic marker compared to the single one.
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Neoplasias da Mama , Histonas , Humanos , Feminino , Histonas/genética , Histonas/metabolismo , Neoplasias da Mama/metabolismo , Lisina/metabolismo , Metilação , PrognósticoRESUMO
Multi-walled carbon nanotubes (MWCNTs) mainly induce oxidative stress through the overproduction of reactive oxygen species (ROS), which can lead to cytotoxicity. Celastrol, a plant-derived compound, can exert antioxidant effects by reducing ROS production. Our results indicated that exposure to MWCNTs decreased cell viability and increased ROS production. Nrf2 knockdown (kd) led to increased ROS production and enhanced MWCNT-induced cytotoxicity. Keap1-kd led to decreased ROS production and attenuated cytotoxicity. Treatment with celastrol significantly decreased ROS production and promoted Keap1 protein degradation through the lysosomal pathway, thereby enhancing the translocation of Nrf2 from the cytoplasm to the nucleus and increasing HO-1 expression. The in vivo results showed that celastrol could alleviate the inflammatory damage of lung tissues, increase the levels of the antioxidants, GSH and SOD, as well as promote the expression of the antioxidant protein, HO-1 in MWCNT-treated mice. Celastrol can alleviate MWCNT-induced oxidative stress through the Keap1/Nrf2/HO-1 signaling pathway.
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Nanotubos de Carbono , Camundongos , Animais , Espécies Reativas de Oxigênio/metabolismo , Nanotubos de Carbono/toxicidade , Fator 2 Relacionado a NF-E2/genética , Fator 2 Relacionado a NF-E2/metabolismo , Proteína 1 Associada a ECH Semelhante a Kelch/genética , Proteína 1 Associada a ECH Semelhante a Kelch/metabolismo , Estresse Oxidativo , Antioxidantes/farmacologia , Antioxidantes/metabolismo , Transdução de SinaisRESUMO
AIMS: To evaluate the ability of carbohydrate antigen 125 (CA125), human epididymis protein 4 (HE4), risk of ovarian malignancy algorithm (ROMA), and Copenhagen Index (CPH-I) to identify primary ovarian cancer (OC) from borderline and benign ovarian tumors (OTs) and explore ideal cutoff points. METHODS: A total of 684 OTs containing 276 OC patients, 116 ovarian borderline OTs and 292 benign OTs patients who underwent surgery in our hospital were included. We retrospectively searched the results of CA125 and HE4 before patients' surgery from the hospital's electronic medical records system. ROMA and CPH-I were calculated according to their menopausal status and age, respectively. Diagnostic performance of these four were assessed by drawing receiver operating characteristic (ROC) curves. RESULTS: CA125, HE4, ROMA, and CPH-I were all significantly higher in OC women compared with borderline OTs (p < 0.001), followed by benign OTs (p < 0.001). Area under the curves (AUCs) for distinguishing OC were 0.850 (0.818-0.882), 0.891 (0.865-0.916), 0.910 (0.888-0.933) and 0.906 (0.882-0.930), respectively, and the corresponding ideal cutoff values for CA125, HE4, ROMA, and CPH-I were 132.5, 68.6, 23.8, and 6.4, respectively. The difference between ROMA and CPH-I was not significant (p = 0.97), but both were higher than CA125 and HE4 (p < 0.05). HE4 showed a significantly higher AUC than CA125 (p < 0.05). For postmenopausal women, CA125 performed equivalently to ROMA (p = 0.73) and CPH-I (p = 0.91). CONCLUSIONS: In identifying patients with OC, ROMA and CPH-I outperformed single tumor marker. The diagnostic performance of HE4 was significantly higher than that of CA125. CA125 was more suitable for postmenopausal women.
Assuntos
Neoplasias Ovarianas , Humanos , Feminino , Estudos Retrospectivos , Neoplasias Ovarianas/patologia , Curva ROC , Algoritmos , Antígeno Ca-125 , Biomarcadores TumoraisRESUMO
PURPOSE: Results of previous studies on the associations between Forkhead box A1 (FOXA1) expression in breast cancer tissues and the prognosis varied depending on the follow-up durations. The present study would investigate whether there is a time-varying effect of FOXA1 in breast cancer tissues on the prognosis. METHODS: FOXA1 expressions were evaluated in 1041 primary invasive breast tumors with tissue microarrays by immunohistochemistry. Cox models with restricted cubic splines and Kaplan-Meier survival analysis were used to examine the associations between FOXA1 and the prognosis. Flexible parametric models were applied to explore the time-varying effect of FOXA1. RESULTS: Overall, the association between FOXA1 expression and the prognosis was not significant but varied on the time of follow-up. Compared to FOXA1 ≤ 270 of H-score, the hazard ratios (HRs) of death for those with 271-285 of FOXA1 expression increased from 0.35 (95% CI 0.14-0.86) at 6 months after diagnosis to 2.88 (95% CI 1.35-6.15) at 120 months with a crossover at around 36 months. Similar patterns were also observed for FOXA1 > 285 of H-score and for progression free survival (PFS). Moreover, when allowed both FOXA1 and estrogen receptor (ER) to change over time in the model (considering that ER had a similar time-varying effect), these time-varying effects remained for FOXA1 on both overall survival (OS) (P < 0.01) and PFS (P = 0.01) but were attenuated for ER (P = 0.13 for OS). CONCLUSIONS: This study revealed an independent time-varying effect of FOXA1 on breast cancer prognosis, which would provide an insight into the roles of FOXA1 as a marker of breast cancer prognosis and may help optimize the medication strategies.
Assuntos
Neoplasias da Mama , Mama , Neoplasias da Mama/genética , Feminino , Fator 3-alfa Nuclear de Hepatócito/genética , Humanos , Prognóstico , Receptores de EstrogênioRESUMO
This study tested the hypothesis that endothelium-specific GTP cyclohydrolase I (GTPCH I) overexpression (Tg-GCH) restores age-associated endothelial dysfunction in vivo. Aortic GTPCH I expression and serum nitric oxide (NO) release were measured in young and aged mice. Aortic rings from young and aged wild-type (WT) mice and aged Tg-GCH mice were suspended for isometric tension recording. A hind limb ischemia model was used to measure blood flow recovery. Aged mice showed reduced GTPCH I expression in the aorta and decreased NO levels in serum. Compared with aged WT mice, Tg-GCH significantly elevated NO levels in serum in aged Tg-GCH mice, restored the impaired aortic relaxation in response to acetylcholine, and significantly elevated aortic constriction in response to L-NAME. Importantly, aged Tg-GCH mice displayed a significant increase in blood flow recovery compared with aged WT mice. GTPCH I reduction contributes to aging-associated endothelial dysfunction, which can be retarded by Tg-GCH.
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A pyrolytic method is described for preparation of ultrafine Fe3C nanoparticles incorporated into N-doped graphitic carbon nanosheets (Fe3C@NGCSs). Iron phthalocyanine and graphitic carbon nitride (g-C3N4) are used as starting materials. The hybrid nanocomposite was placed on a glassy carbon electrode (GCE) and then applied to simultaneous determination of ascorbic acid (AA), dopamine (DA), uric acid (UA) and xanthine (XA). Figures of merits are as follows: for AA, the linear response range covers the 54.0-5491.0 µM range, the lower detection limit is 16.7 µM, and the best working voltage (vs. the saturated calomel electrode (SCE)) is 0.05 V. The respective data for DA are 1.2-120.8 µM, 0.34 µM and 0.19 V (vs. SCE). For UA, the respective data are 4.8-263.0 µM, 1.4 µM and 0.32 V (vs. SCE), and for XA the data are 4.8-361.0 µM, 1.5 µM and 0.71 V (vs. SCE). The method was successfully applied to their simultaneous determination in spiked serum samples. Graphical abstract Ultrafine Fe3C nanoparticles embedded in N-doped graphitic carbon sheets for simultaneous determination of ascorbic acid, dopamine, uric acid and xanthine.
Assuntos
Ácido Ascórbico/análise , Compostos Inorgânicos de Carbono/química , Dopamina/análise , Compostos de Ferro/química , Nanopartículas/química , Ácido Úrico/análise , Xantina/análise , Técnicas Biossensoriais , Carbono/química , Técnicas Eletroquímicas , Eletrodos , Humanos , Tamanho da Partícula , Propriedades de SuperfícieRESUMO
Interleukin 17 (IL-17) plays an important role in the pathogenesis of cardiac interstitial fibrosis. In this study, we explored the role of interleukin-17 in the development of diabetic cardiomyopathy and the underlying mechanisms. The level of IL-17 increased in both the serum and cardiac tissue of diabetic mice. Knockout of IL-17 improved cardiac function of diabetic mice induced by streptozotocin (STZ), and significantly alleviated interstitial fibrosis as manifested by reduced collagen mRNA expression and collagen deposition evaluated by Masson's staining. High glucose treatment induced collagen production were abolished in cultured IL-17 knockout cardiac fibroblasts (CFs). The levels of long noncoding RNA-AK081284 were increased in the CFs treated with high glucose or IL-17. Knockout of IL-17 abrogated high glucose induced upregulation of AK081284. Overexpression of AK081284 in cultured CFs promoted the production of collagen and TGFß1. Both high glucose and IL-17 induced collagen and TGFß1 production were mitigated by the application of the siRNA for AK081284. In summary, deletion of IL-17 is able to mitigate myocardial fibrosis and improve cardiac function of diabetic mice. The IL-17/AK081284/TGFß1 signaling pathway mediates high glucose induced collagen production. This study indicates the therapeutic potential of IL-17 inhibition on diabetic cardiomyopathy disease associated with fibrosis.
Assuntos
Diabetes Mellitus Experimental/genética , Diabetes Mellitus Experimental/fisiopatologia , Testes de Função Cardíaca , Interleucina-17/metabolismo , Miocárdio/metabolismo , Miocárdio/patologia , RNA Longo não Codificante/metabolismo , Animais , Proliferação de Células , Células Cultivadas , Colágeno/metabolismo , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/diagnóstico por imagem , Fibroblastos/metabolismo , Fibroblastos/patologia , Fibrose , Glucose/toxicidade , Interleucina-17/sangue , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Regulação para CimaRESUMO
The transcription factor Forkhead box protein M1 (FOXM1) plays critical roles in cancer development and progression, including human hepatocellular carcinoma (HCC). However, the regulatory role and underlying mechanisms of FOXM1 is still limited. Here, we found that the high level expression of FOXM1 and CCNB1 is closely associated with poor prognosis in HCC patients. And FOXM1 and CCNB1 were overexpressed concomitantly in liver tumor tissues. Knockdown of FOXM1 significantly inhibited the expression levels of CCNB1 in HCC cell lines at both the mRNA and protein levels. Mechanistic studies revealed that FOXM1 binds directly to the promoter region of CCNB1 and regulates the expression levels of the CCNB1 gene in the transcriptional level. Furthermore, the loss of functional and rescue experiments showed that CCNB1 is essential for FOXM1-driven proliferation in HCC cells. In the present study, our results partially explained the dysregulated expression of FOXM1 play an important role in proliferation of human hepatocellular carcinoma cells via transcriptional activation of CCNB1 expression. And it also highlights a FOXM1/CCNB1 axis could be a potential target for the treatment of HCCs.
Assuntos
Carcinoma Hepatocelular/genética , Ciclina B1/genética , Proteína Forkhead Box M1/genética , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/genética , RNA Mensageiro/genética , Sítios de Ligação , Carcinoma Hepatocelular/diagnóstico , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidade , Linhagem Celular Tumoral , Ciclina B1/antagonistas & inibidores , Ciclina B1/metabolismo , Proteína Forkhead Box M1/metabolismo , Células Hep G2 , Humanos , Neoplasias Hepáticas/diagnóstico , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidade , Prognóstico , Regiões Promotoras Genéticas , Ligação Proteica , RNA Mensageiro/antagonistas & inibidores , RNA Mensageiro/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Análise de Sobrevida , Ativação TranscricionalRESUMO
The use of alkaline phosphatase (ALP) as a biomarker in some diseases including hepatitis, obstructive jaundice, osteoblastic bone cancer, and osteomalacia is important in clinical diagnosis. Furthermore, ALP activity detection is an essential hot topic in environmental monitoring, biomedical research, and other research fields. In this study, a novel "signal-on" photoelectrochemical (PEC) biosensor based on the ALP-catalyzed phosphorylation reaction was designed to sensitively detect ALP activity. In this design, ascorbic acid-an electron donor-was catalytically produced by ALP from l-ascorbic acid 2-phosphate trisodium salt in situ, which results in an increased photocurrent response signal. For immobilizing the ALP on the electrode surface, poly diallyl dimethyl ammonium chloride was used for the conjugation of ALP, and titanium dioxide (TiO2)-a photoactive material-and graphite-like carbon nitride (g-C3N4) nanocomposites were prepared and characterized. TiO2 attached on g-C3N4 plays an important role for the biosensing purpose due to their good biocompatibility and chemical/thermal stability, while g-C3N4 provides the PEC response signal. Furthermore, the prepared TiO2/g-C3N4 nanocomposites can effectively suppress electron-hole recombinations, improve the excitation conversion efficiency, and make the best use of solar energy. The PEC biosensor for ALP activity detection displays a detection limit of 0.03 U L-1 (S/N = 3), which offers a new route for the ALP activity assay in human serum samples.
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Allergic asthma is one of the most enduring diseases of the airway. The T-helper cells and regulatory T-cells are critically involved in inflammatory responses, mucus hypersecretion, airway remodelling and in airway hyper-responsiveness. Cigarette smoke (CS) has been found to aggravate inflammatory responses in asthma. Though currently employed drugs are effective, associated side effects demand identification and development of novel drugs with negligible or no adverse effects. Rutin, plant-derived flavonoid has been found to possess antioxidant and anti-inflammatory effects. We investigated the ability of rutin to modulate T-cells and inhibit inflammation in experimentally-induced asthma in cigarette smoke exposed mice. Separate groups of neonatal mice were exposed to CS for 10 days from post-natal days 2 to 11. After 2 weeks, the mice were sensitized and challenged with ovalbumin (OVA). Treatment group were given rutin (37.5 or 75 mg/kg body weight) during OVA sensitization and challenge. Rutin treatment was found to significantly inhibit cellular infiltration in the airways and Th2 and Th17 cytokine levels as well. Flow cytometry revealed effectively raised CD4+CD25+Fox3+ Treg cells and supressed Th17 cell population on rutin treatment. Airway hyper-responsiveness observed following CS and OVA challenge were inhibited by rutin. NF-κB and iNOS, chief regulators of inflammatory responses robustly activated by CS and OVA were down-regulated by rutin. Rutin also inhibited the expression of matrix metalloproteinase 9, thereby aiding in prevention of airway remodelling in asthma thereby revealing to be a potent candidate in asthma therapy.
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The coffee bean weevil (CBW), Araecerus fasciculatus (De Geer, 1775) (Coleoptera: Anthribidae) is an important pest of stored products such as grains, coffee beans, cassava, and traditional Chinese medicine materials. In China, CBW causes large losses of Daqu, a traditional Chinese liquor fermentation starter, and, unfortunately, the use of conventional insecticides against CBW is not suitable in Daqu storage. We found CBW to be highly attracted to fermenting yeast cultures, such as Kluyveromyces lactis. Eight volatile compounds, produced by fermenting cultures and not by sterile samples, were identified by gas chromatography coupled with mass spectrometry. Five of these substances elicited significant responses in Y-tube behavioral bioassays. Field trapping experiments revealed 2-phenylethanol and 2-phenylethyl acetate to be crucial for attraction of CBW. Results show that yeast volatiles play an important role in host location, and that 2-phenylethanol and 2-phenylethyl acetate could be utilized as potential attractants in monitoring and control systems against this important pest.
Assuntos
Comportamento Animal/efeitos dos fármacos , Café/parasitologia , Controle de Insetos/métodos , Kluyveromyces/metabolismo , Compostos Orgânicos Voláteis/farmacologia , Gorgulhos/fisiologia , Animais , Cromatografia Gasosa-Espectrometria de Massas , Sementes/parasitologia , Compostos Orgânicos Voláteis/isolamento & purificação , Compostos Orgânicos Voláteis/metabolismoRESUMO
The coffee bean weevil (CBW), Araecerus fasciculatus (De Geer, 1775), is a cosmopolitan stored-product pest, especially in tropical and subtropical areas. Previous reports showed evidence for aggregation behavior of CBW and this study aimed to identify and evaluate the aggregation pheromone of this pest. Whole-body solvent extractions were analyzed by coupled gas chromatography-mass spectrometry and comparison of male and female extracts showed a male-specific compound which was identified as squalene, 2,6,10,15,19,23-hexamethyl-2,6,10,14,18,22-tetracosahexaene. This compound was shown to attract male and female CBW in Y-tube olfactometer and storage trap assays. The longevity of septum lures was also evaluated in a warehouse. Squalene could be useful in monitoring and controlling this pest.
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Feromônios/metabolismo , Esqualeno/metabolismo , Gorgulhos/fisiologia , Animais , Comportamento Animal , Aglomeração , Controle de Insetos , Masculino , Olfatometria , Feromônios/análise , Olfato , Esqualeno/análise , Gorgulhos/químicaRESUMO
Postmenopausal hypertensive is associated with estrogen deficiency. This meta-analysis was performed to assess the efficacy and safety of drospirenone combined with 17-ß-estradiol (DRSP/E2) in postmenopausal hypertensive women. A systemic literature search of PubMed, Embase, Cochrane Library, Web of Science (up to Oct. 2015) was performed. Studies were screened independently by two researchers according to the inclusion and exclusion criteria which included only the randomized controlled trials (RCT) about the drospirenone with 17-ß-estradiol for postmenopausal women with hypertension. The methodological quality was evaluated by Cochrane handbook 5.1.0 and meta-analysis was conducted using RevMan 5.3.0 software. Five randomized controlled trials involved 1121 patients who met the eligibility criteria. Overall, DRSP/E2 group was superior in reducing clinical blood pressure (BP) and 24-h mean BP. There was no significant change in potassium levels on DRSP/E2 group versus control group, suggesting probability potassium sparing effect of this hormone therapy. The incidences of adverse events were low and similar. The current evidences indicate that DRSP 3 mg/E2 2 mg can significantly lower both systolic and diastolic blood pressure in postmenopausal hypertensive women.
Assuntos
Androstenos/farmacologia , Quimioterapia Combinada , Estradiol/farmacologia , Hipertensão/tratamento farmacológico , Antagonistas de Receptores de Mineralocorticoides/farmacologia , Pós-Menopausa/efeitos dos fármacos , Androstenos/administração & dosagem , Estradiol/administração & dosagem , Feminino , Humanos , Antagonistas de Receptores de Mineralocorticoides/administração & dosagemRESUMO
In this paper, a method of determination of trace lead in water by UV-Visible diffuse reflectance spectroscopy combined with surfactant and membrane filtration enrichment was proposed. In the NH3 x H2O-NH4Cl buffer solution with pH 8.5, the lead(II) ion would react with dithizone to form the red complex under vigorous stirring, which is hydrophobic and can be enriched by the mixed cellulose ester membrane. In addition, the nonionic surfactant Polyoxyethylene lauryl ether (Brij-30) was added into the solution to improve the enrichment efficiency, then visible diffuse reflectance spectra of the membrane were measured directly after the membrane were naturally dried. We also optimized the reaction conditions which may affect the complexation reaction process, such as type of surfactants, the concentration of the surfactant, the reaction acidity, the concentration of dithizone as well as the reaction time. The research results show that under the optimum conditions, a good linear correlation between absorbance at 485 nm and concentration of lead in the range of 5.0-100.0 microg x L(-1) was obtained with a squared correlation coefficient (R2) of 0.9906, and the detection limit was estimated accordingly to be 2.88 microg x L(-1). To determine real water sample, the interference from some potential coexisting ions was also studied at the optimal conditions when the concentration of lead (II) ion standard solution was fixed to 20 microg x L(-1). The results indicate that the following ions cannot interfere in the determination of lead with the proposed method: 500 times of the K+, Na+, Ca2+, Mg2+, NH4+, NO3-, Cl-, CH3COO-, SO4(2-); 10 times of the Al3+ (using 10% NaF as a masking reagent to avoid the interference); 10 times of the Fe3+ (using 10% NaF and 10% sodium potassium tartrate as masking reagents); 10 times of Hg2+ or Zn2+ (using 10% NaSCN and 10% potassium sodium tartrate as masking reagents); the same amount of Cd2+, Cu2+. The proposed method was applied to the determnation of lead (II) in bottled water as a real sample. The determination results show good agreements between the proposed method and graphite furnace atomic absorption spectrometry (GFAAS) method. The recoveries in case of spiked real samples were between 95.4% and 104.5%, and the standard deviations (SD) were between 0.5 micro x L(-1) and 1.5 microg x L(-1), which indicate that the method developed in the present work with advantages of accuracy, simpleness, sensitiveness are of potential application for the determination of trace lead in water samples.
RESUMO
The present paper proposed for the first time the flocculation-filtration method for separation of interfering substances in milk, such as fat. In this method only two steps were carried out. Firstly, aluminum chloride (PAC, Al2 (OH)nCl6-n,) is used to flocculate the milk; Secondly, water filter was used to filter the mixture. Then the clear filtrate could be used for the detection of melamine. The whole preprocessing would not take more than one minute. The pretreatment process was optimized. Experiments show that the adding proportion of PAC should be about 2%-3% for best filtration efficiency, and that it would have the best flocculation effect when the mixture was mildly alkaline. High performance liquid chromatography experiments show that the melamine recovery of this method is more than 90%. Samples pretreated by the flocculation--filtration method were clearer and the baselines of spectral curve obtained by sensitizing Raman method were more smooth which means better purification compared to those samples pretreated by centrifugal pretreatment method. The pretreatment method proposed can be used in HPLC and Raman spectroscopy methods for rapid detecting melamine in liquid milk. This method shows better separation effect, simpler operation, and lower time and money cost than those pretreatment processes in the existing standard melamine detection method for milk. By use of this pretreatment method, the melamine rapid detection efficiency would be greatly improved.