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1.
Inflamm Res ; 73(4): 597-617, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38353723

RESUMO

OBJECTIVE: PANoptosis, a new form of regulated cell death, concomitantly manifests hallmarks for pyroptosis, apoptosis, and necroptosis. It has been usually observed in macrophages, a class of widely distributed innate immune cells in various tissues, upon pathogenic infections. The second-generation curaxin, CBL0137, can trigger necroptosis and apoptosis in cancer-associated fibroblasts. This study aimed to explore whether CBL0137 induces PANoptosis in macrophages in vitro and in mouse tissues in vivo. METHODS: Bone marrow-derived macrophages and J774A.1 cells were treated with CBL0137 or its combination with LPS for indicated time periods. Cell death was assayed by propidium iodide staining and immunoblotting. Immunofluorescence microscopy was used to detect cellular protein distribution. Mice were administered with CBL0137 plus LPS and their serum and tissues were collected for biochemical and histopathological analyses, respectively. RESULTS: The results showed that CBL0137 alone or in combination with LPS induced time- and dose-dependent cell death in macrophages, which was inhibited by a combination of multiple forms of cell death inhibitors but not each alone. This cell death was independent of NLRP3 expression. CBL0137 or CBL0137 + LPS-induced cell death was characterized by simultaneously increased hallmarks for pyroptosis, apoptosis and necroptosis, indicating that this is PANoptosis. Induction of PANoptosis was associated with Z-DNA formation in the nucleus and likely assembly of PANoptosome. ZBP1 was critical in mediating CBL0137 + LPS-induced cell death likely by sensing Z-DNA. Moreover, intraperitoneal administration of CBL0137 plus LPS induced systemic inflammatory responses and caused multi-organ (including the liver, kidney and lung) injury in mice due to induction of PANoptosis in these organs. CONCLUSIONS: CBL0137 alone or plus inflammatory stimulation induces PANoptosis both in vitro and in vivo, which is associated with systemic inflammatory responses in mice.


Assuntos
Carbazóis , DNA Forma Z , Neoplasias , Camundongos , Animais , Lipopolissacarídeos/farmacologia , Apoptose , Piroptose
2.
Lipids Health Dis ; 23(1): 16, 2024 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-38218878

RESUMO

BACKGROUND: Studies have shown that integrating anlotinib with programmed death 1 (PD-1)/programmed death-ligand 1 (PD-L1) inhibitors enhances survival rates among progressive non-small-cell lung cancer (NSCLC) patients lacking driver mutations. However, not all individuals experience clinical benefits from this therapy. As a result, it is critical to investigate the factors that contribute to the inconsistent response of patients. Recent investigations have emphasized the importance of lipid metabolic reprogramming in the development and progression of NSCLC. METHODS: The objective of this investigation was to examine the correlation between lipid variations and observed treatment outcomes in advanced NSCLC patients who were administered PD-1/PD-L1 inhibitors alongside anlotinib. A cohort composed of 30 individuals diagnosed with advanced NSCLC without any driver mutations was divided into three distinct groups based on the clinical response to the combination treatment, namely, a group exhibiting partial responses, a group manifesting progressive disease, and a group demonstrating stable disease. The lipid composition of patients in these groups was assessed both before and after treatment. RESULTS: Significant differences in lipid composition among the three groups were observed. Further analysis revealed 19 differential lipids, including 2 phosphatidylglycerols and 17 phosphoinositides. CONCLUSION: This preliminary study aimed to explore the specific impact of anlotinib in combination with PD-1/PD-L1 inhibitors on lipid metabolism in patients with advanced NSCLC. By investigating the effects of using both anlotinib and PD-1/PD-L1 inhibitors, this study enhances our understanding of lipid metabolism in lung cancer treatment. The findings from this research provide valuable insights into potential therapeutic approaches and the identification of new therapeutic biomarkers.


Assuntos
Carcinoma Pulmonar de Células não Pequenas , Indóis , Neoplasias Pulmonares , Quinolinas , Humanos , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Inibidores de Checkpoint Imunológico/farmacologia , Inibidores de Checkpoint Imunológico/uso terapêutico , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Receptor de Morte Celular Programada 1/uso terapêutico , Lipídeos/uso terapêutico
3.
Arch Virol ; 168(9): 227, 2023 Aug 11.
Artigo em Inglês | MEDLINE | ID: mdl-37566243

RESUMO

Feline coronavirus (FCoV) is the causative agent of feline infectious peritonitis and diarrhoea in kittens worldwide. In this study, a total of 73 feline diarrhoeal faecal samples were collected from animal hospitals and pet markets in ShanDong province from 2017 to 2019. FCoV was detected in 58.23% (46/73) of the samples, using the RT-PCR method. The results showed that the detection rate of FCoV in healthy cats and sick cats was 41.7% (10/24) and 81.6% (40/49), respectively. Full gene amplification and sequencing of the N, M, and S2 genes of FCoV isolates were performed. An amino acid mutation (M1058L) in the S2 gene was found that can be used as a marker for distinguishing feline enteric coronavirus (FECV) from feline infectious peritonitis virus (FIPV). This study provides new epidemiological information about FCoV that will aid in the prevention of FCoV in China.


Assuntos
Infecções por Coronavirus , Coronavirus Felino , Coronavirus Felino/genética , Infecções por Coronavirus/veterinária , Infecções por Coronavirus/virologia , Doenças do Gato/virologia , Animais , Gatos , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas M de Coronavírus/genética , Glicoproteína da Espícula de Coronavírus/genética , Masculino , Feminino
4.
Eur J Nutr ; 62(2): 771-782, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36261730

RESUMO

PURPOSE: Fruit intake is beneficial to several chronic diseases, but controversial in diabetes. We aimed to investigate prospectively the associations of whole fresh fruit intake with risk of incident type 2 diabetes (T2D) in subjects with different glucose regulation capacities. METHODS: The present study included 79,922 non-diabetic participants aged ≥ 40 years from an ongoing nationwide prospective cohort in China. Baseline fruit intake information was collected by a validated food frequency questionnaire. Plasma HbA1c, fasting and 2 h post-loading glucose levels were measured at both baseline and follow-up examinations. Cox proportional hazards models were used to calculate hazard ratio (HR) and 95% confidence intervals (CI) for incident diabetes among participants with normal glucose tolerance (NGT) and prediabetes, after adjusted for multiple confounders. Restricted cubic spline analysis was applied for dose-response relation. RESULTS: During a median 3.8-year follow-up, 5886 (7.36%) participants developed diabetes. Overall, we identified a linear and dose-dependent inverse association between dietary whole fresh fruit intake and risk of incident T2D. Each 100 g/d higher fruit intake was associated with 2.8% lower risk of diabetes (HR 0.972, 95%CI [0.949-0.996], P = 0.0217), majorly benefiting NGT subjects with 15.2% lower risk (HR 0.848, 95%CI [0.766-0.940], P = 0.0017), while not significant in prediabetes (HR 0.981, 95%CI 0.957-4.005, P = 0.1268). Similarly, the inverse association was present in normoglycemia individuals with a 48.6% lower risk of diabetes when consuming fruits > 7 times/week comparing to those < 1 time/week (HR 0.514, 95% CI [0.368-0.948]), but not in prediabetes (HR 0.883, 95% CI [0.762-1.023]). CONCLUSION: These findings suggest that higher frequency and amount of fresh fruit intake may protect against incident T2D, especially in NGT, but not in prediabetes, highlighting the dietary recommendation of higher fresh fruit consumption to prevent T2D in normoglycemia population.


Assuntos
Diabetes Mellitus Tipo 2 , Estado Pré-Diabético , Humanos , Diabetes Mellitus Tipo 2/epidemiologia , Frutas , Estudos Prospectivos , Incidência , Glucose , Fatores de Risco
5.
Inorg Chem ; 61(40): 15801-15805, 2022 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-35913725

RESUMO

Metal-organic frameworks (MOFs) have been a focus of research because of their unique porous structure, but they are usually not directly for electrocatalysis. Herein, we prepared a special class of Fe/Zn/Mo-based trimetallic hybrid zeolitic imidazolate frameworks by in situ solvothermal synthesis that have the potential to act directly as highly efficient oxygen evolution reaction electrocatalysts. This work provides a foundation for the preparation of multimetal MOFs and expands the investigation of electrocatalysts.

6.
Zhongguo Zhong Yao Za Zhi ; 47(14): 3844-3852, 2022 Jul.
Artigo em Zh | MEDLINE | ID: mdl-35850843

RESUMO

We studied the effect of Tianma Gouteng Decoction on vascular aging in spontaneously hypertensive rats(SHRs) to explore the molecular mechanism of the decoction in improving arterial vascular aging by regulating the expression of mitofusin 2(MFN2).Twenty 64-weeks-old SHRs were randomly assigned into the aging group and the treatment group(Tianma Gouteng Decoction 5.48 mg·kg~(-1)).Wistar-Kyoto(WKY) rats of 64 weeks old were taken as the normal group and SHR rats of 14 weeks old as the young group.The intervention with Tianma Gouteng Decoction lasted for 12 weeks.We then employed HE staining and Masson staining to observe the morphology of thoracic aorta under an electron microscope and measured the malondialdehyde(MDA) content, superoxide dismutase(SOD) activity, respiratory chain complex Ⅲ level, and thioredoxin peroxidase(TPX) activity.The vascular aging was detected via the biomarker senescence-associated beta-galactosidase(SA-ß-Gal).The expression levels of MFN2 and aging marker proteins silent information regulator 1(SIRT1), Klotho, p21, and p53 in thoracic aorta were detected by immunohistochemistry/fluorescence, qRT-PCR, and Western blot.Compared with the young group and the normal group, the aging group had risen blood pressure, lumen stenosis caused by thickened intima of blood vessels, decreased SOD and TPX activities, increased MDA and mitochondrial respiratory chain complex Ⅲ levels, down-regulated expression of MFN2, SIRT1, and Klotho, and up-regulated expression of p21 and p53(P<0.01 or P<0.05).The treatment with Tianma Gouteng Decoction significantly lowered blood pressure, mitigated vascular intimal thickening, increased SOD and TPX activities, and decreased MDA and mitochondrial respiratory chain complex Ⅲ levels, thus alleviating vascular aging.At the same time, the decoction up-regulated the expression of MFN2, SIRT1, and Klotho, while down-regulated that of p21 and p53(P<0.01 or P<0.05).In summary, Tianma Gouteng Decoction can significantly delay the vascular aging in hypertension.Specifically, it may up-regulate the expression of MFN2 and regulate the expression of aging-related proteins to alleviate oxidative stress.


Assuntos
Hipertensão , Sirtuína 1 , Envelhecimento/genética , Animais , Medicamentos de Ervas Chinesas , Complexo III da Cadeia de Transporte de Elétrons/metabolismo , Hipertensão/tratamento farmacológico , Hipertensão/genética , Ratos , Ratos Endogâmicos SHR , Ratos Endogâmicos WKY , Sirtuína 1/metabolismo , Superóxido Dismutase/metabolismo , Proteína Supressora de Tumor p53
7.
Inorg Chem ; 60(3): 1305-1309, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33478217

RESUMO

A two-dimensional Ni-heteroatom-based metal-organic framework (MOF) array was directly grown on C paper (Ni-MOF-A/CP) via one-pot solvothermal reaction. According to the strategy for MOF self-assembly on C paper, Ni-MOFs were also synthesized on Ni foam (Ni-MOF/NF) with different sizes and morphologies. The newly resulting MOFs with ternary (Ni, S, and N) active sites exhibited enhanced activity toward oxygen evolution reaction [e.g., Ni-MOF-A/CP: E(5 mA cm-2) = 333 mV and a low Tafel slope of 80 mV dec-1].

8.
Inflammopharmacology ; 29(4): 1187-1200, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34244900

RESUMO

Lagotis brachystachya Maxim is a herb widely used in traditional Tibetan medicine. Our previous study indicated that total extracts from Lagotis brachystachya could lower uric acid levels. This study aimed to further elucidate the active components (luteolin, luteoloside and apigenin) isolated from Lagotis brachystachya and the underlying mechanism in vitro and in vivo. The results showed that treatment with luteolin and luteoloside reversed the reduction of organic anion transporter 1 (OAT1) levels, while apigenin attenuated the elevation of urate transporter 1 (URAT1) and glucose transporter 9 (GLUT9) levels in uric acid-treated HK-2 cells, which was consistent with the finding in the kidneys of potassium oxonate (PO)-induced mice. On the other hand, hepatic xanthine oxidase activity was inhibited by the components. In addition, all of these active components improved the morphology of the kidney in hyperuricemic mice. Moreover, molecular docking showed that luteolin, luteoloside and apigenin could bind Toll-like receptor 4 (TLR4) and NLR family pyrin domain containing 3 (NLRP3). Congruently, western blot analysis showed that the components inhibited TLR4/myeloid differentiation primary response 88 (MyD88)/NLRP3 signaling. In conclusion, these results indicated that luteolin, luteoloside and apigenin could attenuate hyperuricemia by decreasing the production and increasing the excretion of uric acid, which were mediated by inhibiting inflammatory signaling pathways.


Assuntos
Medicamentos de Ervas Chinesas/farmacologia , Hiperuricemia/metabolismo , Rim/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Receptor 4 Toll-Like/metabolismo , Ácido Úrico/metabolismo , Animais , Relação Dose-Resposta a Droga , Medicamentos de Ervas Chinesas/isolamento & purificação , Medicamentos de Ervas Chinesas/uso terapêutico , Homeostase/efeitos dos fármacos , Homeostase/fisiologia , Hiperuricemia/tratamento farmacológico , Rim/efeitos dos fármacos , Masculino , Camundongos , Proteína 3 que Contém Domínio de Pirina da Família NLR/antagonistas & inibidores , Plantas Medicinais , Estrutura Secundária de Proteína , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Receptor 4 Toll-Like/antagonistas & inibidores , Ácido Úrico/toxicidade
9.
Brain Inj ; 34(7): 975-982, 2020 06 06.
Artigo em Inglês | MEDLINE | ID: mdl-32362186

RESUMO

BACKGROUND: To explore the combined influences of temperature-sensitive bone mesenchymal stem cells (tsBMSCs) and mild hypothermia (MH) on neurological function and glucose metabolism in rats with severe traumatic brain injury (TBI). METHODS: SD rats were randomly divided into sham, TBI, TBI + MH, TBI + BMSCs and TBI + MH +tsBMSCs groups. Then, the brain water content, serum-specific proteins (S100ß, NSE, LDH, and CK), and blood glucose at different time points were measured. Furthermore, GLUT-3 expression was detected by Western blotting, and apoptotic rate was determined by TUNEL staining. RESULTS: After TBI rat establishment, the brain injury resulted in significant increases in mNSS scores and brain water content, and upregulations in serum levels of S100ß, NSE, LDH and CK, and blood glucose, with the elevated cell apoptotic rate in the injured cortex. However, these changes were reversed by MH alone, BMSCs alone, or combination treatment of MH and tsBMSCs in varying degrees, and the combination treatment was superior to the treatment with BMSCs or MH alone. CONCLUSION: Combination therapy of tsBMSCs and MH can reduce the neuronal apoptosis in severe TBI rats, with the suppression of serum biomarkers and hyperglycemia, contributing to the recovery of neurological functions. ABBREVIATIONS: tsBMSCs: temperature-sensitive bone mesenchymal stem cells; MH: mild hypothermia; TBI: traumatic brain injury; mNSS: modified Neurological Severity Score.


Assuntos
Lesões Encefálicas Traumáticas , Hipotermia Induzida , Hipotermia , Células-Tronco Mesenquimais , Animais , Lesões Encefálicas Traumáticas/complicações , Lesões Encefálicas Traumáticas/terapia , Ratos , Ratos Sprague-Dawley , Temperatura
10.
Scand J Immunol ; 90(1): e12769, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31006127

RESUMO

Acinetobacter baumannii (A baumannii) is an emerging nosocomial pathogenic bacterium which leads to hospital infections. The increase in drug-resistant A baumannii strains makes it difficult to control by using common antibiotics. The development of effective vaccines is an alternative means to avoid A baumannii infections. In the present study, Balb/c mice were inoculated intratracheally with 30 µg of OmpK/Omp22 fusion protein alone or OmpK/Omp22 formulated with MF59 adjuvant. After two times of boosting at day 14 and 21, the antigen-specific antibody levels and the protective immunity against A baumannii challenge were evaluated. The results showed that the OmpK/Omp22 formulated with MF59 immunized mice produced much higher level of antigen-specific antibodies compared to mice immunized with OmpK/Omp22 alone (P < 0.01). Mice immunized with 30 µg of OmpK/Omp22 formulated with MF59 also provided more potent protection post-challenge, which showed lower bacterial loads in the blood and lung tissue, lower level of blood inflammatory cytokines and higher survival rate (83.3%) than mice immunized with OmpK/Omp22 alone (P < 0.001). In conclusion, this study demonstrated that OmpK/Omp22 fusion protein adjuvanted with MF59 induced superior immune response and better protection than OmpK/Omp22 alone through intratracheal inoculation in mice.


Assuntos
Infecções por Acinetobacter/imunologia , Acinetobacter baumannii/fisiologia , Adjuvantes Imunológicos , Proteínas da Membrana Bacteriana Externa/imunologia , Vacinas Bacterianas/imunologia , Proteínas Recombinantes de Fusão/imunologia , Esqualeno/imunologia , Animais , Carga Bacteriana , Infecção Hospitalar , Citocinas/metabolismo , Humanos , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos BALB C , Polissorbatos , Traqueia/metabolismo , Vacinação
11.
Zhongguo Zhong Yao Za Zhi ; 44(8): 1696-1703, 2019 Apr.
Artigo em Zh | MEDLINE | ID: mdl-31090337

RESUMO

To study the effect of modified Buyang Huanwu Decoction on the hemorrhagic transformation after intravenous thrombolysis of recombinant tissue type plasminogen activator(rt-PA) in patients with super early(onset time<4. 5 h) cerebral infarction. From March 2016 to July 2018,at the brain disease zone of the First Affiliated Hospital of Henan University of Traditional Chinese Medicine,212 cases of super early cerebral infarction were selected and divided into two group according to the randomized complete blocks designs: control group(106 cases) and traditional Chinese medicine group(106 cases). The control group was treated with rt-PA intravenous thrombolysis,while the traditional Chinese medicine group was treated with modified Buyang Huanwu Decoction in addition to the therapy of the control group. Both groups were treated for 14 days. Neurological deficit score,serum matrix metalloproteinase-9(MMP-9),neuron specific enolase(NSE),vascular endothelial growth factor(VEGF) and plasma cellular fibronectin(c-FN) levels,the incidence of hemorrhagic transformation,clinical efficacy and adverse drug reactions before and after treatment were compared between the two groups. According to the findings,at the 14 thday after treatment,the rank sum test of the grade data showed that the clinical efficacy of the traditional Chinese medicine group was better than that of the control group(Z =-2. 033,P = 0. 042); on the basis of χ2 test,the total efficiency of the traditional Chinese medicine group was higher than that of the control group(χ2= 4. 895,P =0. 027); the hemorrhagic transformation rate of the traditional Chinese medicine group was lower than that of the control group within14 days of treatment(χ2= 3. 962,P = 0. 047). MMP-9 levels in the traditional Chinese medicine group were lower than those in the control group at the 3 rd,5 th,7 th,10 th,14 thd after treatment(t =-2. 474,-3. 022,-5. 163,-6. 998,-9. 821; P = 0. 014,0. 003,0,0,0). The improvement of c-FN,NSE,VEGF and NIHSS scores in the traditional Chinese medicine group was superior to that of the control group after 14 days of treatment(t =-2. 343,-3. 187,-2. 129,-3. 105; P = 0. 020,0. 002,0. 034,0. 002). No obvious adverse reactions of modified Buyang Huanwu Decoction were observed during 14 days of treatment. Modified Buyang Huanwu Decoction could reduce the expressions of MMP-9,c-FN,NSE and VEGF after rt-PA intravenous thrombolysis in patients with super early cerebral infarction,and decrease the hemorrhagic transformation rate after thrombolysis,with high safety.


Assuntos
Infarto Cerebral/tratamento farmacológico , Medicamentos de Ervas Chinesas/uso terapêutico , Ativador de Plasminogênio Tecidual/uso terapêutico , Fibronectinas/sangue , Humanos , Metaloproteinase 9 da Matriz/sangue , Medicina Tradicional Chinesa , Fosfopiruvato Hidratase/sangue , Proteínas Recombinantes/uso terapêutico , Terapia Trombolítica , Fator A de Crescimento do Endotélio Vascular/sangue
12.
Zhongguo Dang Dai Er Ke Za Zhi ; 20(8): 647-651, 2018 Aug.
Artigo em Zh | MEDLINE | ID: mdl-30111474

RESUMO

A case of 3-hydroxyisobutyryl-CoA hydrolase deficiency was reported, and its clinical features, gene mutation characteristics, and diagnosis and treatment were analyzed with reference to related literature. The patient aged 1 year and 6 months had developmental regression and paroxysmal dystonia after pyrexia and diarrhea, and head MRI showed symmetrical lesions in the bilateral basal ganglia. No pathogenic mutation was found in the full-length detection of mitochondrial genome. Nuclear gene detection of mitochondrial-related diseases found new compound heterozygous mutations in the HIBCH gene, i.e., c.439-2A>G and c.958A>G (p.K320E), which were inherited from his father and mother, respectively. The boy was given cocktail therapy, dietary valine restriction, and symptomatic treatment. After 2 weeks of treatment, there were improvements in dystonia and motor and intellectual development.


Assuntos
Anormalidades Múltiplas/diagnóstico , Anormalidades Múltiplas/terapia , Erros Inatos do Metabolismo dos Aminoácidos/diagnóstico , Erros Inatos do Metabolismo dos Aminoácidos/terapia , Tioléster Hidrolases/deficiência , Anormalidades Múltiplas/enzimologia , Anormalidades Múltiplas/genética , Erros Inatos do Metabolismo dos Aminoácidos/enzimologia , Erros Inatos do Metabolismo dos Aminoácidos/genética , Sequência de Bases , Humanos , Lactente , Masculino , Dados de Sequência Molecular , Mutação Puntual , Tioléster Hidrolases/genética
13.
Zhong Yao Cai ; 39(8): 1803-8, 2016 Aug.
Artigo em Zh | MEDLINE | ID: mdl-30204388

RESUMO

Objective: To evaluate the quality of Ophiopogonis Radix from produce area, circulation link and clinical application in Sichuan, and to provide the theoretical basis for the quality control of Ophiopogonis Radix in Sichuan. Methods: 105 samples were collected from different produce area, market, factory of decoction pieces, drugstore in Sichuan. The content of moisture,total ash, extractum, total saponin, heavy metal, harmful element, pesticide residues, sulfur dioxide were measured by the methods which recorded in Chinese pharmacopoeia. The content of ophiopogonin D, methylophiopogonanone A, methylophiopogonanone B were measured by HPLC. Results: The content of moisture, total ash, extractum, total saponin in 105 samples Ophiopogonis Radix in Sichuan were at 5. 7%~ 17. 9%,0. 9% ~ 3. 4%,68. 7% ~ 95. 1%,0. 12% ~ 0. 57%,respectively. Over standard rate of sulfur dioxide was 23. 81%. The content of heavy metal and harmful element was conform to the limitation requirement of Chinese pharmacopoeia. Three kinds of organic pesticide had not been checked out. The content of ophiopogonin D, methylophiopogonanone A,methylophiopogonanone B were at 0. 04~ 0. 30 mg/kg,0. 0170 ~ 0. 0837 mg/kg,0. 0049 ~ 0. 0370 mg/kg, respectively. Conclusion: The quality of 105 samples are up to the requirement with the provisions of the Chinese pharmacopoeia. Actually,the mandatory standard was not perfect, especially lack of standard in security. It is suggested that strengthening supervision of sulfur dioxide and paclobutrazol residual according to the actual situation for ensuring the safe and effective of Ophiopogonis Radix in clinical application.

14.
Biochemistry ; 54(1): 32-46, 2015 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-25431995

RESUMO

Mitogen-activated protein kinases-interacting kinase 1 and 2 (Mnk1/2) activate the oncogene eukaryotic initiation factor 4E (eIF4E) by phosphorylation. High level of phosphorylated eIF4E is associated with various types of cancers. Inhibition of Mnk prevents eIF4E phosphorylation, making them potential therapeutic targets for cancer. Recently, we have designed and synthesized a series of novel imidazopyridine and imidazopyrazine derivatives that inhibit Mnk1/2 kinases with a potency in the nanomolar to micromolar range. In the current work we model the inhibition of Mnk kinase activity by these inhibitors using various computational approaches. Combining homology modeling, docking, molecular dynamics simulations, and free energy calculations, we find that all compounds bind similarly to the active sites of both kinases with their imidazopyridine and imidazopyrazine cores anchored to the hinge regions of the kinases through hydrogen bonds. In addition, hydrogen bond interactions between the inhibitors and the catalytic Lys78 (Mnk1), Lys113 (Mnk2) and Ser131 (Mnk1), Ser166 (Mnk2) appear to be important for the potency and stability of the bound conformations of the inhibitors. The computed binding free energies (ΔGPred) of these inhibitors are in accord with experimental bioactivity data (pIC50) with correlation coefficients (r(2)) of 0.70 and 0.68 for Mnk1 and Mnk2 respectively. van der Waals energies and entropic effects appear to dominate the binding free energy (ΔGPred) for each Mnk-inhibitor complex studied. The models suggest that the activities of these small molecule inhibitors arise from interactions with multiple residues in the active sites, particularly with the hydrophobic residues.


Assuntos
Peptídeos e Proteínas de Sinalização Intracelular/antagonistas & inibidores , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Inibidores de Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/metabolismo , Sequência de Aminoácidos , Humanos , Peptídeos e Proteínas de Sinalização Intracelular/química , Dados de Sequência Molecular , Ligação Proteica/fisiologia , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/farmacologia , Proteínas Serina-Treonina Quinases/química , Estrutura Secundária de Proteína
15.
Zhonghua Nan Ke Xue ; 21(8): 713-6, 2015 Aug.
Artigo em Zh | MEDLINE | ID: mdl-26442298

RESUMO

OBJECTIVE: To assess the association of the A260G and A386G single nucleotide polymorphisms (SNP) of the DAZL gene with male infertility in the Chinese population of Zhejiang Province. METHODS: We collected the peripheral blood samples from 317 idiopathic infertile males with azoospermia or oligozoospermia and 246 normal fertile men, and genotyped the polymorphic loci of the A260G and A386G polymorphisms of the DAZL gene using the SNaPshot technique. RESULTS: The DAZL gene A260G was found genetically polymorphic in the Chinese population of Zhejiang Province, with the gene frequencies and their distribution consistent to the Hardy-Weinberg equilibrium. The frequencies of the AA, AG and GG genotypes of the A260G polymorphism were 92.3%, 7.3%, and 0.4% respectively in the normal controls and 94.3%, 5.7%, and 0% in the infertile patients, with no statistically significant differences between the two groups (P = 0.43, OR = 0.78, 95% CI 0.413-1.46). Heterozygosis (AG) of A386G was found in 1 of the control males but not in the infertile patients, while homozygosis (GG) of A386G was not observed in either group (P = 0.259, OR = 0.698, 59% CI: 0.374-1.306). CONCLUSION: A260G and A386G SNPs of the DAZL gene are not associated with spermatogenic failure and neither represents a molecular marker for the genetic diagnosis of male infertility in the Chinese population of Zhejiang Province.


Assuntos
Infertilidade Masculina/genética , Polimorfismo de Nucleotídeo Único , Proteínas de Ligação a RNA/genética , Povo Asiático , Azoospermia/genética , China , Frequência do Gene , Marcadores Genéticos , Genótipo , Humanos , Masculino , Oligospermia/genética , Polimorfismo Genético
16.
J Org Chem ; 79(17): 8059-66, 2014 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-25122518

RESUMO

The key cyclopentenyl intermediate 11b was synthesized in 4 steps from d-ribose in 41% overall yield via an efficient intramolecular Baylis-Hillman reaction. This novel key intermediate can be modified easily and transformed to neplanocin A (1a) and its 3'-epimer (1b).


Assuntos
Adenosina/análogos & derivados , Ciclopentanos/química , Adenosina/síntese química , Adenosina/química , Catálise , Técnicas de Química Combinatória , Estrutura Molecular , Estereoisomerismo
17.
Mol Biol Rep ; 41(8): 5019-30, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24792235

RESUMO

The aim of this study was to explore the effect of lactoferrin (LF) in primary fetal rat osteoblasts proliferation and differentiation and investigate the underlying molecular mechanisms. Primary rat osteoblasts were obtained from the calvarias of neonatal rats. Osteoblasts were treated with LF (0.1-1000 µg/mL), or OSI-906 [a selective inhibitor of insulin-like growth factor 1 (IGF-1) receptor and insulin receptor]. The IGF-1 was then knocked down by small hairpin RNA (shRNA) technology and then was treated with recombinant human IGF-1 or LF. Cell proliferation and differentiation were measured by MTT assay and alkaline phosphatase (ALP) assay, respectively. The expression of IGF-1 and IGF binding protein 2 (IGFBP2) mRNA were analyzed using real-time PCR. LF promotes the proliferation and differentiation of osteoblasts in a certain range (1-100 µg/mL) in time- and dose-dependent manner. The mRNA level of IGF-1 was significantly increased, while the expression of IGFBP2 was suppressed by LF treatment. Knockdown of IGF-1 by shRNA in primary rat osteoblast dramatically decreased the abilities of proliferation and differentiation of osteoblasts and blocked the proliferation and differentiation effect of LF in osteoblasts. OSI906 (5 µM) blocked the mitogenic and differentiation of LF in osteoblasts. Proliferation and differentiation of primary rat osteoblasts in response to LF are mediated in part by stimulating of IGF-1 gene expression and alterations in the gene expression of IGFBP2.

18.
J Sci Food Agric ; 94(10): 2009-15, 2014 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-24307307

RESUMO

BACKGROUND: Heat-induced protein aggregation is important for the texture of various food products. Many types of food proteins have been found to assemble into fibrillar structures under certain conditions. We studied fibril formation of cottonseed 7S storage protein upon heating (for 0-720 min) at 90°C and pH 2.0, investigated the conversion rate, and determined the extent of thermal aggregation. RESULTS: Thioflavin-T fluorescence and Congo-red analysis indicated the formation of amyloid-like fibrils upon heating. Centrifugal filtration indicated that the conversion was very low (<10%) until congossypin concentration up to 2 mg mL(-1), and the conversion increases with increasing heating time, but levels off after longer heating times. Dynamic light scattering and atomic force microscopy showed that the extent of thermal aggregation at pH 2.0, or contour length of the worm-like and fine-stranded aggregates, progressively increased with increasing heating time. Furthermore, reducing electrophoresis analyses indicated that progressive polypeptide hydrolysis occurred upon heating. Experiments indicate that congossypin can form heat-induced amyloid-like aggregates and the conversion of congossypin monomers into fibrils increased with heating time and protein concentration. CONCLUSION: The results would be of vital importance for the utilisation of cottonseed proteins to produce thermally induced fibrillar gels with excellent properties.


Assuntos
Gossypium/química , Temperatura Alta , Proteínas de Plantas/química , Sementes/química , Amiloide , Tecnologia de Alimentos , Géis , Humanos , Concentração de Íons de Hidrogênio , Hidrólise
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 34(4): 967-71, 2014 Apr.
Artigo em Zh | MEDLINE | ID: mdl-25007610

RESUMO

The aim is analyzing genetic reLationship and identifying varieties by detecting DNA differences of three kinds of Nicotiana tabacum L. using Fourier infrared spectrum (FTIR). Results show that DNA FTIR of three kinds of Nicotiana tabacum L. is relatively similar. They all have four obvious characteristic peaks. 1 105 cm(-1) beLongs to symmetrical stretching vibration of phosphodiester bond, 1 250 cm(-1) is unsymmetrical stretching vibration of phosphodiester bond, 1 400 cm(-1) is contributed to glucosidic bond, and 1 622 cm(-1) belongs to C4-C5=C6 stretching vibration of cytosine. DNA FTIR data was handled by smoothing, standardizing, second derivative, principal component analysis and Hierarchical cluster analysis. The standard model of Hierarchical cluster combined with principal component of the second derivative was set up. The correct rate of identification is 100%. Yunyan 87 and K326 were clustered into one by using the model. The distance coefficient is 0.003, and DNA similarity is 99.7%, Hongda was clustered into one by itself. The correct rate of cluster is 100%. The study provides a reference for Nicotiana tabacum L. variety identification and genetic breeding.


Assuntos
Nicotiana/genética , Espectroscopia de Infravermelho com Transformada de Fourier , Análise por Conglomerados , DNA de Plantas/análise , Análise de Componente Principal
20.
Zhongguo Zhong Yao Za Zhi ; 39(19): 3865-9, 2014 Oct.
Artigo em Zh | MEDLINE | ID: mdl-25612456

RESUMO

Asteraceae Echionopos (Echinops genus) is one of the world's plants commonly used in traditional Chinese medicine herbs. In this paper, a lot of literature on the basis of domestic and foreign, and modern research on the application of medicinal plants in different ethnic groups in our country Echionopos made a brief presentation and evaluation, and its in Chinese Han, Mongolian, Uygur, Kazak, Korean and other ethnic groups in the application of traditional medicine and related research conducted profiles. To further comprehensive and accurate use of the abundant plant resources and research, in order to find biologically active natural products, provide reference basis for the clinical application of new drugs developed and expanded drug source.


Assuntos
Asteraceae/química , Medicamentos de Ervas Chinesas/farmacologia , Animais , Tratamento Farmacológico , Medicamentos de Ervas Chinesas/química , Humanos , Medicina Tradicional Chinesa
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