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Aim: The response of E. coli ATCC8739 to Brevinin-2CE (B2CE) was evaluated as a strategy to prevent the development of antimicrobial peptide (AMP)-resistant bacteria. Methods: Gene expression levels were detected by transcriptome sequencing and RT-PCR. Target genes were knocked out using CRISPR-Cas9. MIC was measured to evaluate strain resistance. Results: Expression of acrZ and sugE were increased with B2CE stimulation. ATCC8739ΔacrZ and ATCC8739ΔsugE showed twofold and fourfold increased sensitivity, respectively. The survival rate of ATCC8739 was reduced in the presence of B2CE/chlorpromazine (CPZ). Combinations of other AMPs with CPZ also showed antibacterial effects. Conclusion: The results indicate that combinations of AMPs/efflux pump inhibitors (EPIs) may be a potential approach to combat resistant bacteria.

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Antibacterianos , Clorpromazina , Escherichia coli , Pruebas de Sensibilidad Microbiana , Escherichia coli/efectos de los fármacos , Escherichia coli/genética , Escherichia coli/metabolismo , Antibacterianos/farmacología , Clorpromazina/farmacología , Proteínas de Escherichia coli/genética , Proteínas de Escherichia coli/metabolismo , Farmacorresistencia Bacteriana/efectos de los fármacos , Farmacorresistencia Bacteriana/genética , Péptidos Antimicrobianos/farmacología , Péptidos Antimicrobianos/genética , Proteínas Anfibias/genética , Proteínas Anfibias/farmacología , Proteínas Anfibias/metabolismo , Péptidos Catiónicos Antimicrobianos/farmacología , Sinergismo Farmacológico

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Objective To investigate the impact of silymarin(SM)on the malignant growth of glioma cells and the regulatory mechanism on the miR-124-3p/WEE1 axis.Methods Glioma U87 cells were grouped into control,SM low,medium,and high concentration groups,and SM high concentration + miR-124-3p inhibitor group(SM high + miR-124-3p inhibitor group).CCK-8 was used to measure the proli-feration rate of cells;Transwell? assay was applied to assay the migration and invasion of cells;cell cycle progression was detected by flow cytometry;Western blotting was applied to measure the expression of cyclin D1 and apoptosis-related proteins;the levels of miR-124-3p and WEE1 mRNA were determined by qRT-PCR;and a luciferase activity test was applied to verify the targeting relationship between miR-124-3p and WEE1;in addition,the establishment,administration,and analysis of a NOD/SCID mouse model of intracranial trans-planted tumor were conducted.Results Compared with the control group,the cell proliferation,the numbers of migrating and invading cells,the expression of cyclin D1,and the level of WEE1 mRNA in the various SM treatment groups decreased,the number of cells in G0/G1 phase,the expression of cleaved caspase-8,cleaved caspase-9,cleaved caspase-3 and miR-124-3p increased(P＜0.05);furthermore,transfection of miR-124-3p inhibitor reversed the inhibitory effect of SM on the malignant behavior of glioma cells.In vivo experiments with mice showed that the weights and volumes of tumors in the SM treatment group were lower than those in the model group(P＜0.05),and there was no discernible change in the weight of the mice(P＞0.05).Conclusion SM can inhibit the malignant growth of glioma cells by upregulating miR-124-3p and downregulating WEE1.

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The purpose of this study was to investigate the effect of aqueous extract of Corni Fructus on β-amyloid protein 25-35(Aβ_(25-35))-induced brain injury and neuroinflammation in Alzheimer's disease(AD) mice to provide an experimental basis for the treatment of AD by aqueous extract of Corni Fructus. Sixty C57BL/6J male mice were randomly divided into a sham group, a model group, a positive control group(huperizine A, 0.2 mg·kg~(-1)), a low-dose aqueous extract of Corni Fructus group(1.3 g·kg~(-1)), a medium-dose aqueous extract of Corni Fructus group(2.6 g·kg~(-1)), and a high-dose aqueous extract of Corni Fructus group(5.2 g·kg~(-1)). The AD model was induced by lateral ventricular injection of Aβ_(25-35) in mice except for those in the sham group, and AD model mice were treated with corresponding drugs by gavage for 24 days. The behavioral test was performed one week before animal dissection. Hematoxylin-eosin(HE) staining was performed to observe the morphology of neurons in the hippocampal region. Flow cytometry was used to detect the apoptosis level of primary hippocampal cells in mice. ELISA kits were used to detect the levels of β-amyloid protein 1-42(Aβ_(1-42)) and phosphorylated microtubule-associated protein Tau(p-Tau) in mouse brain tissues. Immunofluorescence and Western blot were used to detect the expression of related proteins in mouse brain tissues. MTT assay was used to detect the effect of compounds in aqueous extract of Corni Fructus on Aβ_(25-35)-induced N9 cell injury. Molecular docking was employed to analyze the interactions of caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol with β-amyloid precursor protein(APP), interleukin-6(IL-6), and tumor necrosis factor-α(TNF-α). Aqueous extract of Corni Fructus could improve the learning and memory abilities of Aβ_(25-35)-induced mice by increasing the duration of the autonomous activity, the rate of autonomous alternation, the preference coefficient, and the discrimination coefficient, and reduce Aβ_(25-35)-induced brain injury and neuroinflammation in mice by increasing the expression levels of interleukin-10(IL-10) and B-cell lymphoma-2(Bcl-2) in brain tissues, decreasing the expression levels of Aβ_(1-42), p-Tau, IL-6, TNF-α, cysteine aspartate-specific protease 3(caspase-3), cysteine aspartate-specific protease 9(caspase-9), and Bcl-2-associated X protein(Bax), and decreasing the number of activated glial cells in brain tissues. The results of cell experiments showed that esculetin and(+)-lyoniresinol could improve Aβ_(25-35)-induced N9 cell injury. Molecular docking results showed that caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol had good binding affinity with APP and weak binding affinity with IL-6 and TNF-α. Aqueous extract of Corni Fructus could ameliorate cognitive dysfunction and brain damage in Aβ_(25-35)-induced mice by reducing the number of apoptotic cells and activated glial cells in the brain and decreasing the expression level of inflammatory factors. Caffeic acid, trans-p-hydroxy cinnamic acid, isolariciresinol-9'-O-β-D-glucopyranoside, esculetin, and(+)-lyoniresinol may be the material basis for the anti-AD effect of aqueous extract of Corni Fructus.

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Ratones , Masculino , Animales , Enfermedad de Alzheimer/tratamiento farmacológico , Péptidos beta-Amiloides/metabolismo , Cornus/metabolismo , Enfermedades Neuroinflamatorias , Factor de Necrosis Tumoral alfa/metabolismo , Interleucina-6 , Ácido Aspártico , Cisteína/uso terapéutico , Simulación del Acoplamiento Molecular , Ratones Endogámicos C57BL , Lesiones Encefálicas , Péptido Hidrolasas , Modelos Animales de Enfermedad , Ratones Transgénicos

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The present study aimed to investigate the protective effect and underlying mechanism of Platycladi Semen oil(SP) on Aβ_(25-35)-induced brain injury in mice to provide a theoretical basis for the clinical treatment of Alzheimer's disease(AD). Male Kunming(KM) mice were randomly divided into a control group, a model group(brain injection of Aβ_(25-35), 200 μmol·L~(-1), 0.15 μL·g~(-1)), a positive drug group(donepezil, 10 mg·kg~(-1)), and low-and high-dose SP groups(0.5 and 1 mL·kg~(-1)). Learning and memory ability, neuronal damage, levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, related indicators of apoptosis and oxidative stress, and immune cells, and protein and mRNA expression related to the sphingosine kinase 1(SPHK1)/sphingosine-1-phosphate(S1P)/sphingosine-1-phosphate receptor 5(S1PR5) signaling pathway of mice in each group were determined. In addition, compounds in SP were analyzed by gas chromatography-mass spectrometry(GC-MS). The mechanism of SP against AD was investigated by network pharmacology, 16S rDNA gene sequencing for gut microbiota(GM), and molecular docking techniques. The results showed that SP could improve the learning and memory function of Aβ_(25-35)-induced mice, reduce hippocampal neuronal damage, decrease the levels of Aβ_(1-42)/Aβ_(1-40), p-Tau, and indicators related to apoptosis and oxidative stress in the brain, and maintain the homeostasis of immune cells and GM. Network pharmacology and sequencing analysis for GM showed that the therapeutic effect of SP on AD was associated with the sphingolipid signaling pathway. Meanwhile,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid, the components with the highest content in SP, showed good binding activity to SPHK1 and S1PR5. Therefore, it is inferred that SP exerts anti-apoptosis and antioxidant effects by regulating GM and inhibiting SPHK1/S1P/S1PR5 pathway, thereby improving brain injury induced by Aβ_(25-35) in mice. Moreover,(Z,Z,Z)-9,12,15-octadecatrienoic acid and(Z,Z)-9,12-octadecadienoic acid may be the material basis for the anti-AD effect of SP.

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Ratones , Animales , Masculino , Semen/metabolismo , Microbioma Gastrointestinal , Farmacología en Red , Ácido Linoleico , Simulación del Acoplamiento Molecular , Enfermedad de Alzheimer/genética , Lesiones Encefálicas

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This study aimed to investigate the effect and mechanisms of Ephedra Herb (EH) extract on adriamycin-induced nephrotic syndrome (NS), providing an experimental basis for the clinical treatment of NS. Hematoxylin and eosin staining, creatinine, urea nitrogen, and kidn injury molecule-1 were used to evaluate the activities of EH extract on renal function. The levels of inflammatory factors and oxidative stress were detected by kits. The levels of reactive oxygen species, immune cells, and apoptosis were measured by flow cytometry. A network pharmacological approach was used to predict the potential targets and mechanisms of EH extract in the treatment of NS. The protein levels of apoptosis-related proteins and CAMKK2, p-CAMKK2, AMPK, p-AMPK, mTOR and p-mTOR in the kidneys were detected by Western blot. The effective material basis of EH extract was screened by MTT assay. The AMPK pathway inhibitor (compound C, CC) was added to investigate the effect of the potent material basis on adriamycin-induced cell injury. EH extract significantly improved renal injury and relieve inflammation, oxidative stress, and apoptosis in rats. Network pharmacology and Western blot results showed that the effect of EH extract on NS may be associated with the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine significantly ameliorated adriamycin-induced NRK-52e cell injury. Methylephedrine also significantly improved the phosphorylation of AMPK and mTOR, which were blocked by CC. In sum, EH extract may ameliorate renal injury via the CAMKK2/AMPK/mTOR signaling pathway. Moreover, methylephedrine may be one of the material bases of EH extract.

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Ratas , Animales , Doxorrubicina/efectos adversos , Síndrome Nefrótico , Proteínas Quinasas Activadas por AMP/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Apoptosis

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Objective: To investigate the distribution of HIV-1 genetic subtypes and pretreatment drug resistance (PDR) among men who have sex with men (MSM) from 19 cities of 6 provinces in China. Methods: From April to November 2019, 574 plasma samples of ART-naive HIV-1 infected MSM were collected from 19 cities in Hebei, Shandong, Jiangsu, Zhejiang, Fujian, and Guangdong provinces, total ribonucleic acid (RNA) was extracted and amplified the HIV-1 pol gene region by nested polymerase chain reaction (PCR) after reverse transcription. Then sequences were used to construct a phylogenetic tree to determine genetic subtypes and submitted to the Stanford drug resistance database for drug resistance analysis. Results: A total of 479 samples were successfully amplified by PCR. The HIV-1 genetic subtypes included CRF01_AE, CRF07_BC, B, CRF55_01B, CRF59_01B, CRF65_cpx, CRF103_01B, CRF67_01B, CRF68_01B and unrecognized subtype, which accounted for 43.4%, 36.3%, 6.3%, 5.9%, 0.8%, 0.8%, 0.4%, 0.4%, 0.2% and 5.5%, respectively. The distribution of genetic subtypes among provinces is statistically different (χ2=44.141, P<0.001). The overall PDR rate was 4.6% (22/479), the drug resistance rate of non-nucleoside reverse transcriptase inhibitors, nucleoside reverse transcriptase inhibitors, and protease inhibitors were 3.5% (17/479), 0.8% (4/479) and 0.2% (1/479), respectively. The PDR rate of recent infections was significantly higher than that of long-term infections (χ2=4.634, P=0.031). Conclusions: The HIV-1 genetic subtypes among MSM infected with HIV-1 from 19 cities of 6 provinces in China are diverse, and the distribution of subtypes is different among provinces. The overall PDR rate is low, while the PDR rate of recent infections was significantly higher than that of long-term infections, suggesting the surveillance of PDR in recent infections should be strengthened.

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Femenino , Humanos , Masculino , China/epidemiología , Ciudades , Resistencia a Medicamentos , Farmacorresistencia Viral/genética , Genotipo , Infecciones por VIH/epidemiología , Seropositividad para VIH/tratamiento farmacológico , VIH-1/genética , Homosexualidad Masculina , Filogenia , Inhibidores de la Transcriptasa Inversa/uso terapéutico , Minorías Sexuales y de Género

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Fifteen compounds were isolated from fruits of Cornus officinalis by various chromatographic techniques such as Toyopearl HW-40C, Sephadex LH-20, silica gel, and the semi-preparative HPLC. Their chemical structures were identified by analysis of physicochemical properties and spectral data, and determined as neolignan A (1), caffeic acid (2), trans-p-hydroxy cinnamic acid (3), esculetin (4), scopoletin (5), benzyl-7-O-β-D-glucopyranoside (6), tachioside (7), 6-O-(4-hydroxybenzoyl) arbutin (8), 2-(3′,4′-dihydroxyphenyl)-1,3-benzodioxole-5-carboxaldehyde (9), (-)-pinoresinol-4-O-β-D-glucopyranoside (10), (7S,8R)-dihydrodehydrodiconiferyl alcohol-9-O-β-D-glucopyranoside (11), (7S,8R)-dihydrodehydrodiconiferyl alcohol-9′-O-β-D-glucopyranoside (12), (+)-lyoniresinol (13), (+)-isolariciresinol-9-O-β-D-glucopyranoside (14), and isolariciresinol-9′-O-β-D-glucopyranoside (15). Compound 1 was a new compound and named as neolignan A, and compounds 6-9 and 14 were isolated from Cornus officinalis for the first time. Compounds 2, 3 and 15 efficiently alleviated the PC12 cells injury induced by Aβ25-35, suggesting their potential anti-Alzheimer's disease activity.

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Objective:To analyze the monitoring results of plague foci in Guizhou Province, to master the epidemic dynamics of the plague and to formulate the prevention and control measures.Methods:The plague monitoring data from 2018 to 2020 in Guizhou Province were collected from China Disease Prevention and Control Information System Plague Prevention and Control Information Management System to analyze the plague epidemic situation. The murine animals capture methods used were cage clip method, 5 m cage clip method and day-by-day rodent capture method. Bacterial culture and hemagglutination were used in laboratory.Results:A total of 2 273 murine animals were captured indoors with cage clip method, and the Rattus norvegicus was the dominant species, accounting for 47.29% (1 075/2 273), Rattus flavipectus and Mus musculus were common species, accounting for 43.55% (990/2 273) and 5.10% (116/2 273). A total of 1 460 murine animals were captured outdoors with 5 m cage clip method, and the Rattus rattus sladoni was the dominant species, accounting for 35.48% (518/1 460), Rattus flavipectus and Eothenomys miletus were common species, accounting for 16.03% (234/1 460) and 8.70% (127/1 460). A total of 5 742 murine animals (including 3 733 animals captured with cage clip method and 5 m cage clip method, 2 009 animals captured with day-by-day rodent capture method) were examined and 1 176 with flea, the flea infestation rate of murine animals was 20.48%, Xenopsylla cheopi was the dominant flea species [56.63% (3 020/5 333)] and the index was 0.53. Laboratory test results were all negative. Conclusions:The plague foci of Guizhou Province is at a quiescent stage, but the reignition cannot be ruled out. The monitoring of plague should be strengthened, the quality of the monitoring should be improved, and health education and publicity should be carried out to prevent the occurrence of human plague outbreaks.

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Piperis Fructus is the dried nearly ripe or ripe fruit of Piperaceae, which is an important spice material and a traditional Chinese medicine (TCM), it is widely used in the world. It is recorded to possess the efficacy of warming spleen and stomach for dispelling cold, depressing Qi and dissolving phlegm. Piperis Fructus mainly contains amide alkaloids with piperine as the main ingredient and volatile oil dominated by monoterpenoids and sesquiterpenoids, which have a wide range of biological activities, such as anti-cancer, anti-oxidation, anti-inflammatory, etc. By referring to relevant papers at home and abroad, the researches on chemical compositions from different parts and pharmacological effects of Piperis Fructus in recent 5 years were summarized and analyzed. It was found that Piperis Fructus has great potential for drug development as a TCM with homology of medicine and food, which can provide a reference for further research and comprehensive utilization of Piperis Fructus.

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Objective In the wide clinical practice of liver 3D printing, its related high-dose CT radiation has been somehow neglected and resulted in unnecessary radiation injury to the patients. This study was to explore the feasibility of liver 3D modeling printing with the low-dose radiation CT scanning technique.　Methods　This retrospective study included 40 patients undergoing liver 3D modeling printing from January 2016 to June 2018, who were equally randomized into a low-dose radiation group (100 kVp, by automated tube current modulation [ATCM] and adaptive statistical iterative reconstruction [ASIR]) and a normal-dose radiation group (120 kVp, 250 mA by filter back projection [FBP]), both with contrast agent Iohexol at 300 mgI/m1. We obtained the values of three-phase enhanced CT scanning of the abdominal aorta, portal vein and liver parenchyma, background noise (BN), volume CT dose index (CTDI), dose length product (DLP), contrast noise ratio (CNR) and effective radiation dose (ED). We input the CT DICOM data into the 3D printer for liver modeling printing and subjectively assessed the results. Results There were statistically significant differences between the low-dose and normal-dose radiation groups in the CTDI, DLP and ED (P 0.05). The ED was decreased about 35.8% in the low-dose group as compared with that in the normal-dose group ([2.58 ± 0.79] vs [4.02 ± 0.26] mSv, P 0.05). Conclusion Low-dose radiation CT scanning technology can meet the clinical requirement of liver 3D modeling printing and significantly reduce the patient’s exposure to CT radiation.

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The aim of the present study was to analyze the role of leucine­rich repeat­containing G­protein coupled receptor 6 (Lgr6) in the proliferation and invasion of colorectal cancer (CRC) cells, and to investigate its possible mechanisms. The expression of Lgr6 in CRC tissues was observed by real time­quantitative polymerase chain reaction and western blotting. Then cell viability, apoptosis and cell invasion was measured by MTT, flow cytometry or Matrigel­Transwell system, respectively in CRC cells after transfected with Lgr6 siRNA or Lgr6 vector. Furthermore, the expression of apoptosis­associated protein and PI3K/AKT signaling (phosphorylated­PI3K, phosphorylated­AKT, t­PI3K, t­AKT) were measured by real­time PCR/or western blot analysis. The results demonstrated that the level of Lgr6 was higher in CRC tissues than that in adjacent tissues, and Lgr6 overexpression increased CRC proliferation, and invasion of CRC cells in vitro. Notably, suppressing the expression of Lgr6 in CRC cells increased the expression of B­cell lymphoma-2 (Bcl­2)­associated X protein and caspase­3, but decreased the expression of Bcl­2 at the mRNA and protein levels. Lgr6 also had the ability to regulate the phosphoinositide 3­kinase/AKT signaling pathway. It was concluded that Lgr6 has a tumor­promoting role in the development of CRC, and may serve as a potential diagnostic and prognostic biomarker for the disease.

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Apoptosis , Neoplasias Colorrectales/genética , Neoplasias Colorrectales/patología , Regulación hacia Abajo/genética , Receptores Acoplados a Proteínas G/genética , Adulto , Anciano , Anciano de 80 o más Años , Línea Celular Tumoral , Proliferación Celular , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Silenciador del Gen , Humanos , Estimación de Kaplan-Meier , Masculino , Persona de Mediana Edad , Invasividad Neoplásica , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Receptores Acoplados a Proteínas G/metabolismo , Transducción de Señal , Regulación hacia Arriba/genética

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<p><b>OBJECTIVE</b>To discuss the hemiarthroplasty for the threatment of femoral intertrochanteric fracture in elderly patients.</p><p><b>METHODS</b>From August 2013 to January 2017, 66 elderly patients with complicated femoral intertrochanteric fracture were treated including 20 males and 46 females with an average age of 85 years old ranging from 80 to 95. According to improve Evans classification, 33 cases were type III, 24 cases were type IV, 9 cases were type V. History included 31 cases of hypertension, 10 cases of diabetes, 12 cases of severe osteoporosis, 5 cases of atrial fibrillation, 3 cases of pulmonary heart disease, and 1 case of multiple myeloma. Hip hemiarthroplasty was used in 34 cases and internal fixation in 32 cases. The bleeding volume, complications and Harris scores of the two groups were observed and compared.</p><p><b>RESULTS</b>The amount of blood loss during and after operation were(320±20) ml and(200±25) ml in the joint replacement group, and (350±30) ml and(250±30) ml in the internal fixation group, and there was no statistical difference between the two groups(>0.05). All patients were followed up for an average of 2 years. The Harris score of the joint replacement group was 85.0±6.4, which was higher than that of the internal fixation group (72.0±3.4)(<0.05). The difference of complications between the two groups was statistically significant (<0.05).</p><p><b>CONCLUSIONS</b>The elderly patients with femoral intertrochanteric fractures have many basic diseases, and the expected survival time is short. Using artificial bipolar femoral head prosthesis can restore the hip function early and to the maximum degree, make the patients get down in the bed early, effectively reduce the complications caused by internal fixation, improve the patient's quality of life and satisfaction, and early treatment. It is a kind of supplemental treatment, which conforms to the theory of rapid rehabilitation surgery and injury control, but should not expand the indication and strengthen the management of the perioperative period.</p>

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Objective To analyze the diagnostic value of ultrasonographic calcification on benign and malignant thyroid nodules. Methods The clinical data of 133 thyroid nodules diagnosed in our hospital from January 2015 to June 2017 by ultrasound examination and surgical or biopsy were retrospectively analyzed. Compared the correlation between the characteristics of calcified foci of thyroid nodules and benign and malignant nodules. Results In 133 patients, 176 thyroid nodules were found by ultrasound, including 71 (40. 34％) nodules with calcification and 105 (59. 66％) nodules without calcification. A total of 112 benign nodules(63. 64％) and 64 malignant nodules(36. 36％) were found by pathological diagnosis. The incidence of malignant nodules in calcified thyroid nodules (77. 46％) was significantly higher than that in no-calcified thyroid nodules (7. 62％), and the difference was statistically significant (P＜0. 05). Among 38 nodules with calcified calcification, the incidence of malignant nodules was 94. 74％ (36/38); the incidence of malignant nodules in 23 nodules with calcified calcification was 47. 83％ (11/23) There was a statistically significant difference between the two groups(P＜0. 05). The incidence of calcification in malignant thyroid nodules was 87. 50％(56/64) significantly higher than that in benign thyroid nodules(13. 39％, 15/112) (P＜0. 05). Conclusion The characteristics of calcification under ultrasonography are of great value in the diagnosis of benign and malignant thyroid nodules. In particular, microcalcification calcification can be used as one of the specific indicators of screening for malignant thyroid nodules. It is worthy of clinical promotion.

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OBJECTIVE:To investigate clinical efficacy of Sofren injection combined with Vinpocetine injection in the treatment of acute massive cerebral infarction,and its effects on hemorheological indexes and serum NOS.METHODS:A total of 60 patients with acute massive cerebral infarction in our hospital during Jan.2014-Jun.2016 were selected as research objects and divided into trial group and control group according to random number table,with 30 cases in each group.Control group was given Citicoline injection 0.5 g,ivgtt,qd.Trial group was additionally given Vinpocetine injection 20 mg added into 0.9％ Sodium chloride injection 250 mL,ivgtt,qd;1 h later washing tube,they were given Sofren injection 10 mL added into 0.9％ Sodium chloride injection 250 mL,ivgtt,for consecutive 14 d.Clinical efficacies and safety of 2 groups were observed,and hemorheological indexes and NOS levels were observed before and after treatment.RESULTS:The total response rate (83.33％)of trial group was significantly higher than that (50.00％) of control group,with statistical significance (P＜0.05).Before treatment,there was no statistical significance in hemorheological indexes or serum NOS levels between 2 groups (P＞0.05).After treatment,hemorheological indexes of 2 groups were decreased significantly,and the trial group was significantly lower than the control group.The level of serum NOS in 2 groups were increased significantly,and the trial group was significantly higher than the control group,with statistical significance (P＜0.05).No obvious ADR was found in 2 groups.CONCLUSIONS:Sofren injection combined with Vinpocetine injection show significant therapeutic efficacy for acute massive cerebral infarction,can reduce blood viscosity and increase blood perfusion with good safety.

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Objective To explore the reparation role of recombinant human bone morphogenetic protein-4 mature peptide (rhBMP-4m) on hematopoietic system injury induced by irradiation in mice.Methods Ninety BALB/c mice were randomly divided into normal control group,model group and rhBMP-4m treatment group,with 30 mice in each group.The mice in model group and rhBMP-4m treatment group were irradiated by 60Co γ-ray(7.5 Gy) for 200 s;while the mice in normal control group did not receive irradiation.After irradiation,the mice in model group were given physiological saline 1.0 mL by peritoneal injection per day for 6 days;the mice in rhBMP-4m treatment group were given rhBMP-4m 0.5 mg by peritoneal injection per day for 6 days.The peripheral white blood cell count and marrow mononuclear cells,the percent of CD34 + cells in marrow mononuclear cells of mice were detected on the first,third,fifth,seventh,ninth day after irradiation;the number of spleen nodus and the pleen weight/body weight ratio were detected at the ninth day after irradiation.Results There was no statistic difference in the number of peripheral white blood cells of mice among the three groups on the first day after irradiation(P ＞ 0.05).The peripheral white blood cell count of mice in model group was significantly lower than that in the normal control group on the third,fifth,seventh,ninth day after irradiation (P ＜ 0.01).There was no statistic difference in the number of peripheral white blood cells of mice between rhBMP-4m treatment group and model group on the third,fifth day after irradiation (P ＞ 0.05);the peripheral white blood cell count of mice in rhBMP-4m treatment group was significantly higher than that in model group on the seventh,ninth day after irradiation (P ＜ 0.05).The number of marrow mononuclear cells of mice in model group was significantly lower than that in the normal control group at each time piont after irradiation(P ＜ 0.05).There was no statistic difference in the number of marrow mononuclear cells of mice between the rhBMP-4m treatment group and model group on the first,third day after irradiation (P ＞ 0.05);the number of marrow mononuclear cells of mice in rhBMP-4m treatment group was significantly higher than that in the model group on the fifth,seventh,ninth day after irradiation(P ＜ 0.05).The proportion of CD34 + cells in mononuclear cells of mice in model group was significantly lower than that in the normal control group at each time piont after irradiation(P ＜0.01).There was no statistic difference in the proportion of CD34 + cells in mononuclear cells of mice between the rhBMP-4m treatment group and model group on the first,third day after irradiation (P ＞ 0.05);the proportion of CD34 + cells in mononuclear cells of mice in rhBMP-4m treatment group was significantly higher than that in the model group on the fifth,seventh,ninth day after irradiation(P ＜ 0.05).Compared with the normal control group,the number of spleen nodus was increased and the spleen weight/body weight ratio of mice was decreased in model group on the ninth day after irradiation(P ＜ 0.05);the number of spleen nodus and the spleen weight/body weight ratio of mice in rhBMP-4m treatment group were significantly higher than those in the model group on the ninth day after irradiation (P ＜ 0.01).Conclusion rhBMP-4m can accelerate the reconstruction of bone marrow hematopoietic system of mice with hematopoietic system injury induced by irradiation.

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Objective@#To investigate the changes in protein expression in patients with 1-bromopropane (1-BP) poisoning using high-throughput proteomic technique and to screen out protein markers.@*Methods@#Serum samples were collected from 3 patients with 1-BP poisoning and 15 controls. The label-free proteomic tech-nique was used for the quantitation and identification of proteins expressed in these samples, and the results were compared between the patients with 1-BP poisoning and the control population. The bioinformatics tools were used to analyze the function of differentially expressed proteins.@*Results@#Compared with the control popula-tion, the patients with 1-BP poisoning had >2-fold upregulation of 38 proteins and >2-fold downregulation of 68 proteins. The differentially expressed proteins were mainly involved in immune response, signal transduction, and stress response.@*Conclusion@#The proteins screened out may be potential protein markers for 1-BP poison-ing, which provides reliable and precise methods and thoughts for the diagnosis of 1-BP poisoning.

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The bursa of Fabricius (BF) is the acknowledged central humoral immune organ in birds. Bursal septpeptide II (BSP-II) is an immunomodulatory bioactive peptide isolated from BF. To understand the effects of BSP-II on immune induction, gene expression profiles of hybridoma cells treated with BSP-II were evaluated. Pathway analysis showed that regulated genes were involved in cytokine-cytokine receptor interactions, T cell receptor signaling pathway, and pathway in cancer. It was observed that BSP-II reduced tumor cells proliferation and stimulated p53 expression. These results indicate potential mechanisms underlying the effects of the humoral immune system on immune induction, including antitumor activities. Our study has provided a novel insight into immunotherapeutic strategies for treating human tumors.

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Animales , Antineoplásicos/farmacología , Proteínas Aviares/farmacología , Bolsa de Fabricio/inmunología , Proliferación Celular/efectos de los fármacos , Pollos/inmunología , Hibridomas/efectos de los fármacos , Factores Inmunológicos/farmacología , Análisis de Secuencia por Matrices de Oligonucleótidos/veterinaria , Transducción de Señal/efectos de los fármacos , Transcriptoma

RESUMEN

Abstract: Our previous work revealed berberine can significantly enhance the susceptibility of fluconazole against fluconazole-resistant Candida albicans, which suggested that berberine has synergistic antifungal activity with fluconazole. Preliminary SAR of berberine needs to be studied for the possibility of investigating its target and SAR, improving its drug-likeness, and exploring new scaffold. In this work, 13-substitutited benzyl berberine derivatives and N-benzyl isoquinoline analogues were synthesized and characterized by 1H NMR and MS. Their synergetic activity with fluconazole against fluconazole-resistant Candida albicans was evaluated in vitro. The 13-substitutited benzyl berberine derivatives 1a-1e exhibited comparable activity to berberine, which suggested that the introduction of functional groups to C-13 can maintain its activity. The N-benzyl isoquinolines, which were designed as analogues of berberine with its D ring opened, exhibited lower activity than berberine. However, compound 2b, 2c, and 4b showed moderate activity, which indicated that berberine may be deconstructed to new scaffold with synergistic antifungal activity with fluconazole. The results of our research may be helpful to the SAR studies on its other biological activities.

Asunto(s)

Antifúngicos , Farmacología , Berberina , Farmacología , Candida albicans , Farmacorresistencia Fúngica , Sinergismo Farmacológico , Fluconazol , Farmacología , Isoquinolinas , Farmacología , Pruebas de Sensibilidad Microbiana

RESUMEN

BACKGROUND: Administration of androgens decreases plasma concentrations of high-density lipid cholesterol (HDL-C). However, the mechanisms by which androgens mediate lipid metabolism remain unknown. This present study used HepG2 cell cultures and ovariectomized C57BL/6 J mice to determine whether apolipoprotein M (ApoM), a constituent of HDL, was affected by dihydrotestosterone (DHT). METHODS: HepG2 cells were cultured in the presence of either DHT, agonist of protein kinase C (PKC), phorbol-12-myristate-13-acetate (PMA), blocker of androgen receptor flutamide together with different concentrations of DHT, or DHT together with staurosporine at different concentrations for 24 hrs. Ovariectomized C57BL/6 J mice were treated with DHT or vehicle for 7d or 14d and the levels of plasma ApoM and livers ApoM mRNA were measured. The mRNA levels of ApoM, ApoAI were determined by real-time RT-PCR. ApoM and ApoAI were determined by western blotting analysis. RESULTS: Addition of DHT to cell culture medium selectively down-regulated ApoM mRNA expression and ApoM secretion in a dose-dependent manner. At 10 nM DHT, the ApoM mRNA levels were about 20% lower than in untreated cells and about 40% lower at 1000 nM DHT than in the control cells. The secretion of ApoM into the medium was reduced to a similar extent. The inhibitory effect of DHT on ApoM secretion was not blocked by the classical androgen receptor blocker flutamide but by an antagonist of PKC, Staurosporine. Agonist of PKC, PMA, also reduced ApoM. At 0.5 µM PMA, the ApoM mRNA levels and the secretion of ApoM into the medium were about 30% lower than in the control cells. The mRNA expression levels and secretion of another HDL-associated apolipoprotein AI (ApoAI) were not affected by DHT. The levels of plasma ApoM and liver ApoM mRNA of DHT-treated C57BL/6 J mice were lower than those of vehicle-treated mice. CONCLUSIONS: DHT directly and selectively down-regulated the level of ApoM mRNA and the secretion of ApoM by protein kinase C but independently of the classical androgen receptor.

Asunto(s)

Apolipoproteínas , Dihidrotestosterona , Metabolismo de los Lípidos/efectos de los fármacos , Lipocalinas , Proteína Quinasa C/metabolismo , Animales , Apolipoproteínas/biosíntesis , Apolipoproteínas/sangre , Apolipoproteínas/metabolismo , Apolipoproteínas M , HDL-Colesterol/metabolismo , Dihidrotestosterona/metabolismo , Dihidrotestosterona/farmacología , Regulación hacia Abajo , Expresión Génica/efectos de los fármacos , Células Hep G2 , Humanos , Lipocalinas/biosíntesis , Lipocalinas/sangre , Lipocalinas/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Ésteres del Forbol/farmacología , Proteína Quinasa C/antagonistas & inhibidores , ARN Mensajero/biosíntesis , ARN Mensajero/metabolismo , Receptores Androgénicos/metabolismo

RESUMEN

Objective To investigate the effect of agonist CD40 monoclonal antibody (CD40mAb) on the tolerance of experimental autoimmune myasthenia gravis (EAMG) induced by immature dendritic cells (iDCs). Methods Lewis rats were equally randomized into normal group,EAMG group, tolerance group and CD40mAb treatment group (n=5). Rats in the tolerance group and CD40mAb treatment group were vaccinated with AChR pulsed iDCs; and rats in the CD40mAb treatment group were intraperitoneally injected CD40mAb at a dosage of 0.5 mg once when performing the vaccination and on the 2rd d of vaccination. One mL serum-free medium was given to the rats in the EAMG group; normal group did not receive any treatment. Three weeks after that, rats in the above 4 groups were immunized with AChR and complete Freund's adjuvant (CFA). Seven weeks after the immunization, the corresponding indexes of MG were observed: behavioral assessment was performed and electromyogram was employed to detect the repetitive nerve stimulation on these rats; enzyme-linked immunosorbent assay (ELISA) was used to determine the level of AChRab; the pathological changes of neuromuscular junction were also detected. Results Just as the rats in the normal group, the rats in the tolerance group did not have significant changes in any of the corresponding indexes of MG after being immunized with AChR and CFA. In contrast, rats in both EAMG group and CD40mAb treatment group showed typical changes in the corresponding indexes of MG: their electromyogram wave amplitude obviously attenuated; the level of serum AChRab increased and neuromuscular junction appeared as a typical damage of MG. Conclusion Agonist CD40mAb could abrogate the tolerance of EAMG induced by AChR pulsed iDCs, suggesting that the dysfunction of DCs is related to the priming of abnormal immune of MG.