RESUMEN

OBJECTIVES: To establish the epidemiology cut-off (ECOFF) values of eravacycline against Escherichia coli, Klebsiella pneumoniae, Enterobacter cloacae, Acinetobacter baumannii and Staphylococcus aureus, from a multi-centre study in China. METHODS: We collected 2500 clinical isolates from five hospitals in China from 2017 to 2020. The MICs of eravacycline were determined using broth microdilution. The ECOFF values of eravacycline against the five species commonly causing cIAIs were calculated using visual estimation and ECOFFinder following the EUCAST guideline. RESULTS: The MICs of eravacycline against all the strains were in the range of 0.004-16 mg/L. The ECOFF values of eravacycline were 0.5 mg/L for E. coli, 2 mg/L for K. pneumonia and E. cloacae, and 0.25 mg/L for A. baumannii and S. aureus, consistent with the newest EUCAST publication of eravacycline ECOFF values for the populations. No discrepancy was found between the visually estimated and 99.00% ECOFF values calculated using ECOFFinder. CONCLUSIONS: The determined ECOFF values of eravacycline against the five species can assist in distinguishing wild-type from non-wild-type strains. Given its promising activity, eravacycline may represent a member of the tetracycline class in treating cIAIs caused by commonly encountered Gram-negative and Gram-positive pathogens.

Asunto(s)

RESUMEN

Phosphorylation site prediction has important application value in the field of bioinformatics. It can act as an important reference and help with protein function research, protein structure research, and drug discovery. So, it is of great significance to propose scientific and effective calculation methods to accurately predict phosphorylation sites. In this study, we propose a new method, Attenphos, based on the self-attention mechanism for predicting general phosphorylation sites in proteins. The method not only captures the long-range dependence information of proteins but also better represents the correlation between amino acids through feature vector encoding transformation. Attenphos takes advantage of the one-dimensional convolutional layer to reduce the number of model parameters, improve model efficiency and prediction accuracy, and enhance model generalization. Comparisons between our method and existing state-of-the-art prediction tools were made using balanced datasets from human proteins and unbalanced datasets from mouse proteins. We performed prediction comparisons using independent test sets. The results showed that Attenphos demonstrated the best overall performance in the prediction of Serine (S), Threonine (T), and Tyrosine (Y) sites on both balanced and unbalanced datasets. Compared to current state-of-the-art methods, Attenphos has significantly higher prediction accuracy. This proves the potential of Attenphos in accelerating the identification and functional analysis of protein phosphorylation sites and provides new tools and ideas for biological research and drug discovery.

Asunto(s)

RESUMEN

The identification of transcription factor binding sites (TFBSs) is crucial for understanding the regulatory mechanisms of gene expression, which contributes to unraveling cellular functions and disease development. Currently, the most common approach involves the use of deep learning techniques to predict TFBSs by combining sequence and shape features. Although significant progress has been made with these methods, the integration of local features extracted from DNA sequences and shapes with global features has not yet reached a sufficient level, and there is still significant room for improvement in the accuracy of prediction results. In this paper, we propose a novel framework based on convolution and attention mechanisms, referred to as TBCA, which combines DNA sequence information and shape information for predicting transcription factor binding sites. In this work, we employ a two-layer convolutional neural network (CNNs) and self-attention mechanism to extract complex sequence features from DNA. What's more, we utilize a Fourier-transform-enhanced multi-head attention along with channel attention to extract high-order shape features of DNA. Finally, these high-order sequence and shape features are integrated into the channel dimension to achieve accurate TFBSs prediction. Our research results demonstrate that TBCA exhibits superior predictive performance in 165 validated ChIP-seq datasets. Furthermore, the employed attention mechanisms can automatically learn important features at different positions and scales, enhancing the accuracy and robustness of feature representation. We also conduct an in-depth analysis of the contributions of five different shapes to site prediction, revealing that shape features can enhance the prediction of transcription factor DNA binding.

RESUMEN

Objective: To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs). Methods: A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute. Results: Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum ß-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium, Enterococcus faecalis, S. epidermidis, and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs. Conclusion: The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.

Asunto(s)

RESUMEN

OBJECTIVE@#To investigate the distribution and antimicrobial susceptibility of causative microorganisms recovered from patients with intra-abdominal infections (IAIs).@*METHODS@#A total of 2,926 bacterial and fungal strains were identified in samples collected from 1,679 patients with IAIs at the Peking Union Medical College Hospital between 2011 and 2021. Pathogenic bacteria and fungi were identified using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Antimicrobial susceptibility testing (AST) was performed using the VITEK 2 compact system and the Kirby-Bauer method. AST results were interpreted based on the M100-Ed31 clinical breakpoints of the Clinical and Laboratory Standards Institute.@*RESULTS@#Of the 2,926 strains identified, 49.2%, 40.8%, and 9.5% were gram-negative bacteria, gram-positive bacteria, and fungi, respectively. Escherichia coli was the most prevalent pathogen in intensive care unit (ICU) and non-ICU patients; however, a significant decrease was observed in the isolation of E. coli between 2011 and 2021. Specifically, significant decreases were observed between 2011 and 2021 in the levels of extended-spectrum β-lactamase (ESBL)-producing E. coli (from 76.9% to 14.3%) and Klebsiella pneumoniae (from 45.8% to 4.8%). Polymicrobial infections, particularly those involving co-infection with gram-positive and gram-negative bacteria, were commonly observed in IAI patients. Moreover, Candida albicans was more commonly isolated from hospital-associated IAI samples, while Staphylococcus epidermidis had a higher ratio in community-associated IAIs. Additionally, AST results revealed that most antimicrobial agents performed better in non-ESBL-producers than in ESBL-producers, while the overall resistance rates (56.9%-76.8%) of Acinetobacter baumanmii were higher against all antimicrobial agents than those of other common gram-negative bacteria. Indeed, Enterococcus faecium, Enterococcus faecalis, S. epidermidis, and S. aureus were consistently found to be susceptible to vancomycin, teicoplanin, and linezolid. Similarly, C. albicans exhibited high susceptibility to all the tested antifungal drugs.@*CONCLUSION@#The distribution and antimicrobial susceptibility of the causative microorganisms from patients with IAIs were altered between 2011 and 2021. This finding is valuable for the implementation of evidence-based antimicrobial therapy and provides guidance for the control of hospital infections.

Asunto(s)

RESUMEN

In order to solve the problem of difficult separation of various biogenic amines (BAs), which have similar structures or very different polarities, in gentamicin, by conventional liquid chromatography, a new ultrahigh-performance supercritical fluid chromatography (UHPSFC) method was developed. In this method, 10 BAs were derivatized precolumn using dansyl chloride and separated using a UHPSFC system. By computational simulation, complete separation of 10 BAs was successfully achieved. Detection was performed using a photodiode array (PDA) and single-quadrupole mass spectrometry (MS) together with electrospray ionization (ESI). A wide linear range (10-2500 ng/mL) was achieved, with the limits of detection (LODs) between 1.2 and 10.0 ng/mL and the limits of quantification (LOQs) between 5.0 and 25.0 ng/mL. Apart from high sensitivity, this UHPSFC-PDA/ESI-MS detection method also displayed high accuracy, the matrix effect was reduced by an appreciable extent, and the recovery rates of the 10 BAs were between 84.1 and 117.1%. For comparison, high-performance liquid chromatography-tandem mass spectrometry (MS/MS) was also used for the detection of underivatized BAs in gentamicin, showing good linearity and high sensitivity (LODs from 0.05 to 1.00 ng/mL and LOQs from 1.00 to 12.50 ng/mL) for all BAs except for spermine and spermidine. Although single-quadrupole MS is inferior to MS/MS in terms of sensitivity, the UHPSFC method could detect more BAs. It also achieved the quantification limits required for impurity determination, demonstrating a potential strategy to offer a map overview of possible BA presence in fermentation antibiotics.

Asunto(s)

RESUMEN

Bovine respiratory disease complex (BRDC) is a serious disease affecting feedlot cattle in China and likely other places worldwide. Bovine viral diarrhea virus (BVDV) and bovine parainfluenza virus type 3 (BPIV3) are principally responsible for causing BRDC, and are a major strain to the industrial economy. Eradication of these viruses/disease requires swift viral identification and treatment. Hence, this study established a fast and easy procedure of BVDV and BPIV3 identification that employs reverse transcription recombinase polymerase amplification (RT-RPA) and lateral flow dipstick (LFD), and uses primers and lateral flow (LF) probe targeting the 5'-UTR gene of BVDV and phosphoprotein P gene of BPIV3, respectively. Our assay was able to successfully amplify BVDV and BPIV3 RNA within 25 min at 35 °C using RT-RPA, with products visible on the LFD within 5 min at room temperature (RT). The lowest detection limits were 50 RNA molecules for BVDV and 34 RNA molecules for BPIV3 per reaction. We also demonstrated that the established dual RT-RPA LFD assay was precise and targeted, harboring excellent potential to become an onsite molecular diagnostic tool in the detection of BVDV and BPIV3. This method can detect BVDV (Pestivirus A, B) and BPIV3, and exhibit no cross-reaction with other viruses like the classical swine fever virus (CSFV) and infectious bovine rhinotracheitis virus (IBRV). The assay performance was further assessed with clinical samples, and demonstrated good performance in comparison to real-time RT-PCR (RT-qPCR). Moreover, the RT-RPA LFD assay was comparitively rapid and required minimal training.

Asunto(s)

RESUMEN

Aim To investigate the curative effects of resveratrol on OVA induced allergic rhinitis in mice and the underlying immune mechanisms. Methods Balb/c mice (female, 6 weeks) were divided randomly into normal control ( NC) group, allergic rhinitis (AR) group, high dose resveratrol treatment group (RH), low dose resveratrol treatment group (RL), and dexamethasone treatment group ( Dex). RL, RH and Dex group were oral administered with resveratrol 30 mg • kg"1, resveratrol 100 mg • kg"1 and dexamethasone 10 mg • kg"1, respectively. After the treat-ment , the sneezing and nasal rubbing behaviors of mice in all the group were recorded and HE was performed to assess the inflammatory cell infiltration in nasal tissues. The sera levels of allergic cytokines were determined with ELISA assay. The percentage of CD4+ GA- TA3 + T cells in spleen of each group was further recorded by flow cytometry. Results Compared with AR group, treatment with resveratrol (100 mg - kg"1) reduced the sneezing and nasal rubbing behaviors signifi-cantly and improved inflammatory cell infiltration in nasal tissues. The up-regulated sera levels of IL-4, IL- 13 and OVA-sIgE in AR group were reversed by RH, and ratios CD4+ GATA3 + Th2 cells in spleen of RH were also down-regulated parallelly. Conclusions RH treatment could improve the allergic related symptoms of OVA-induced allergic rhinitis, which is associated with down-regulated sera levels of IL-4, IL-13 and OVA-sIgE and ratios of CD4+ GATA3 + Th2 cells in spleen of mouse model.

RESUMEN

Successful cloning by somatic cell nuclear transfer (SCNT) requires overcoming significant epigenetic barriers. Genomic imprinting is not generally regarded as such a barrier, although H3K27me3-dependent imprinting is differentially distributed in E6.5 epiblast and extraembryonic tissues. Here we report significant enhancement of SCNT efficiency by deriving somatic donor cells carrying simultaneous monoallelic deletion of four H3K27me3-imprinted genes from haploid mouse embryonic stem cells. Quadruple monoallelic deletion of Sfmbt2, Jade1, Gab1, and Smoc1 normalized H3K27me3-imprinted expression patterns and increased fibroblast cloning efficiency to 14% compared with a 0% birth rate from wild-type fibroblasts while preventing the placental and body overgrowth defects frequently observed in cloned animals. Sfmbt2 deletion was the most effective of the four individual gene deletions in improving SCNT. These results show that lack of H3K27me3 imprinting in somatic cells is an epigenetic barrier that impedes post-implantation development of SCNT embryos and can be overcome by monoallelic imprinting gene deletions in donor cells.

Asunto(s)

RESUMEN

BACKGROUND: Expansins (EXPs), a group of proteins that loosen plant cell walls and cellulosic materials, are involved in regulating cell growth and diverse developmental processes in plants. However, the biological functions of this gene family in cotton are still unknown. RESULTS: In this paper, we identified a total of 93 expansin genes in Gossypium hirsutum. These genes were classified into four subfamilies, including 67 GhEXPAs, 8 GhEXPBs, 6 GhEXLAs, and 12 GhEXLBs, and divided into 15 subgroups. The 93 expansin genes are distributed over 24 chromosomes, excluding Ghir_A02 and Ghir_D06. All GhEXP genes contain multiple exons, and each GhEXP protein has multiple conserved motifs. Transcript profiling and qPCR analysis revealed that the expansin genes have distinct expression patterns among different stages of cotton fibre development. Among them, 3 genes (GhEXPA4o, GhEXPA1A, and GhEXPA8h) were highly expressed in the initiation stage, 9 genes (GhEXPA4a, GhEXPA13a, GhEXPA4f, GhEXPA4q, GhEXPA8f, GhEXPA2, GhEXPA8g, GhEXPA8a, and GhEXPA4n) had high expression during the fast elongation stage, and GhEXLA1c and GhEXLA1f were preferentially expressed in the transition stage of fibre development. CONCLUSIONS: Our results provide a solid basis for further elucidation of the biological functions of expansin genes in relation to cotton fibre development and valuable genetic resources for future crop improvement.

Asunto(s)

RESUMEN

With the widespread use of traditional Chinese medicine(TCM) and the integration of TCM and western medicine, drug-drug interaction(DDI) is considered as a major cause of therapeutic failures and side effects. Cytochrome P450 enzymes(CYPs) are responsible for large number of drug metabolism. CYP3 A4 and CYP2 D6, two important CYP isoforms, are responsible for about 80% drug metabolism of CYPs super family. The inhibition of CYPs is likely to be the most common factor leading to adverse DDI. Therefore, it is of great significance to predict potential CYP3 A4 and CYP2 D6 inhibitors to prevent the DDI. A fast and low-cost me-thod for calculating and predicting CYP inhibiting components was established in this paper, namely support vector machine(SVM) and molecular docking technology which are used to predict and screen drugs. Firstly, 12 qualitative models of two targets were established by using SVM, and the optimal model was selected to predict the compounds in traditional Chinese medicine database(TCMD). Then, molecular docking technology was used to establish docking model. By analyzing the key amino acids involved in drug-target interactions and combining with SVM model, potential inhibitors of CYP3 A4 and CYP2 D6 were found. From the computational results, astin D and epiberberine exhibited inhibition effect on CYP3 A4 and CYP2 D6, respectively. Astin D was only found in astins family from Aster tataricus, while epiberberine was considered to be the active constituent of Coptidis Rhizoma. Therefore, for the risk of DDI, extra attention should be paid to the source of these potential inhibitors, Asteris Radix et Rhizoma and Coptidis Rhizoma. This computational method provides technical support for discovering potential natural inhibitors of CYPs from Chinese herbs by using SVM and molecular docking model, and it is also helpful to recognize the CYPs-mediated DDI existing in TCM, providing research ideas for further pharmacovigilance of integrated therapy.

Asunto(s)

RESUMEN

OBJECTIVE: To investigate the effects of ginsenoside-Rg2 on mechanical allodynia, heat hyperalgeia, depressive state of rats with chronic sciatic nerve constriction injury. METHODS: Fifty SD rats were randomly divided into 5 groups: blank control group (Normal, normal + saline),sham operation group (Sham, sham operation + saline),chronic constriction injury of the sciatic nerve group (CCI, CCI + saline),ginsenoside-Rg2 low dose group (CCI + Rg2 5 mg/kg), and ginsenoside-Rg2 high dose group (CCI + Rg2 10 mg/kg).After the CCI model was established,drug were injected into the abdominal cavity through the syringe once a day,for 14 consecutive days.The mechanical shrinkage foot reflex threshold (MWT) and thermal withdrawal latency(TWL) were determined at 1 d before the operation and at 1,3,5,7,10 and 14 d after the operation.Light-dark transition test, forced swimming test were determined at 1 d before the operation and at 14 d after the operation. RESULTS: Compared with the sham group, the MWL and TWL of the CCI rats were decreased significantly (P＜0.01), time in the light compartment and number of transition were decreased (P＜0.01), the immobility time in FST was also prolonged significantly (P＜0.01). At 14 days after CCI operation, the MWL and TWL of the ginsenoside-Rg2 groups were increased significantly (P＜0.01), time in the light compartment and number of transition were also shortened significantly (P＜0.01), the immobility time in FST was also shortened significantly (P＜0.01). CONCLUSION: Intraperitoneal injection of ginsenoside-Rg2 can inhibit the mechanical and thermal pain sensitivity of CCI rats,and can relieve depressive state.

Asunto(s)

RESUMEN

Chemical investigation of the rhizomes of Polygonatum sibiricum Red. led to the identification of 27 constituents. Among them, a total of 16 compounds were obtained from Polygonatum for the first time, in which, 3 and 4 were also firstly isolated as natural products. Anti-inflammatory activity studies on 13 isolated compounds showed that ß-carboline constituents, especially compounds 1 and 2, significantly inhibited the expression of NO, TNF-α, IL-6 and IL-1ß in lipopolysaccharide (LPS)-treated RAW264.7 macrophage cells. Moreover, western blotting analysis demonstrated that compound 1 significantly inhibited the expression of COX-2, iNOS and the activation of NF-κB, suggesting that ß-carboline structures may play an important role in inhibition of NF-κB signaling pathway, which thereby inhibits the production of inflammatory factors. The present research may not only help further elucidation of the anti-inflammatory mechanism of P. sibiricum Red., but also provide the potential bioactive molecules for inflammatory diseases research.

Asunto(s)

RESUMEN

OBJECTIVE@#To investigate the effects of ginsenoside-Rg on mechanical allodynia, heat hyperalgeia, depressive state of rats with chronic sciatic nerve constriction injury.@*METHODS@#Fifty SD rats were randomly divided into 5 groups: blank control group (Normal, normal + saline),sham operation group (Sham, sham operation + saline),chronic constriction injury of the sciatic nerve group (CCI, CCI + saline),ginsenoside-Rg low dose group (CCI + Rg 5 mg/kg), and ginsenoside-Rg high dose group (CCI + Rg 10 mg/kg).After the CCI model was established,drug were injected into the abdominal cavity through the syringe once a day,for 14 consecutive days.The mechanical shrinkage foot reflex threshold (MWT) and thermal withdrawal latency(TWL) were determined at 1 d before the operation and at 1,3,5,7,10 and 14 d after the operation.Light-dark transition test, forced swimming test were determined at 1 d before the operation and at 14 d after the operation.@*RESULTS@#Compared with the sham group, the MWL and TWL of the CCI rats were decreased significantly (P＜0.01), time in the light compartment and number of transition were decreased (P＜0.01), the immobility time in FST was also prolonged significantly (P＜0.01). At 14 days after CCI operation, the MWL and TWL of the ginsenoside-Rg groups were increased significantly (P＜0.01), time in the light compartment and number of transition were also shortened significantly (P＜0.01), the immobility time in FST was also shortened significantly (P＜0.01).@*CONCLUSION@#Intraperitoneal injection of ginsenoside-Rg can inhibit the mechanical and thermal pain sensitivity of CCI rats,and can relieve depressive state.

Asunto(s)

RESUMEN

Objective To explore the roles of frequency domain OCT in measuring the retinal thickness around the optic disc and optic disc parameters in early glaucoma diagnosis.Methods The optic disc parameters and retinal nerve fiber layer (RNFL) thickness in the 40 healthy volunteers (control group) and 85 cases of primary open angle glaucoma (POAG),including 36 patients as the early glaucoma subgroup and 49 patients as the glaucoma evolutum subgroup,were measured by frequency domain OCT.Then,the correlation analysis of RNFL thickness,optic disc parameters and the mean deviation (MD) of visual field in each group was performed,and the area under the curve was used to evaluate the diagnostic efficiency of RNFL thickness around the optic disc and optic disc parameters in the diagnosis of glaucoma.Results The RNFL thickness and the complete cycle mean RNFL thickness in the temporal,upper,nasal and inferior quadrant in the glaucoma patients were significantly lower than those in the controls (all P ＜ 0.05),and the above indexes in the glaucoma evolutum subgroup were significantly decreased compared with those in the early glaucoma subgroup (all P ＜ 0.05).There were statistically significant differences in the optic disc parameters between the groups except the optic disc area (all P ＜ 0.05).Pearson correlation analysis showed the RNFL thickness and the complete cycle mean RNFL thickness in the temporal,upper and inferior quadrant were negatively correlated with the MD in the glaucoma patients (all P ＜ 0.05),and the parameter of optic cup volume and cup/disc area ratio were positively correlated with the MD (both P ＜ 0.05),and the rim area,rim volume and disc volume were negatively correlated with MD (all P ＜ 0.05).The ROC curve analysis showed that the largest area under the curve of RNFL thickness in the inferior quadrant of the optic disc region was 0.886,and the specificity and sensitivity was 0.775 and 0.924,respectively.Moreover,the area under the curve of the optic cup/optic disc area was the largest,with sensitivity and specificity of 0.741 and 0.815,respectively.Conelusion OCT for measuring optic disc structure and RNFL thickness can be used for early diagnosis of glaucoma,and it has a high sensitivity and specificity.

RESUMEN

Pinctada fucata oligopeptide is one of key pharmaceutical effective constituents of P. fucata. It is significant to analyze its pharmacological effect and mechanism. This study aims to discover the potential oligopeptides from P. fucata and analyze the mechanism of P. fucata oligopeptide based on in silico technologies and protein interaction network(PIN). First, main protein sequences of P. fucata were collected, and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then, key potential targets of P. fucata oligopeptides were obtained through pharmacophore screening. The protein-protein interaction(PPI) of targets was achieved and implemented to construct PIN and analyze the mechanism of P. fucata oligopeptides. P. fucata oligopeptide database was constructed based on in silico technologies, including 458 oligopeptides. Twelve modules were identified from PIN by a graph theoretic clustering algorithm Molecular Complex Detection(MCODE) and analyzed by Gene ontology(GO) enrichment. The results indicated that P. fucata oligopeptides have an effect in treating neurological diseases, such as Alzheimer's disease. In silico proteolysis could be used to analyze the protein sequences of traditional Chinese medicine(TCM). According to the combination of in silico proteolysis and PIN, the biological activity of oligopeptides could be interpreted rapidly based on the known TCM protein sequence. The study provides the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides.

Asunto(s)

RESUMEN

Oligopeptides are one of the the key pharmaceutical effective constituents of traditional Chinese medicine(TCM). Systematic study on composition and efficacy of TCM oligopeptides is essential for the analysis of material basis and mechanism of TCM. In this study, the potential anti-hypertensive oligopeptides from Glycine max and their endothelin receptor A (ETA) antagonistic activity were discovered and predicted based on in silico technologies.Main protein sequences of G. max were collected and oligopeptides were obtained using in silico gastrointestinal tract proteolysis. Then, the pharmacophore of ETA antagonistic peptides was constructed and included one hydrophobic feature, one ionizable negative feature, one ring aromatic feature and five excluded volumes. Meanwhile, three-dimensional structure of ETA was developed by homology modeling methods for further docking studies. According to docking analysis and consensus score, the key amino acid of GLN165 was identified for ETA antagonistic activity. And 27 oligopeptides from G. max were predicted as the potential ETA antagonists by pharmacophore and docking studies.In silico proteolysis could be used to analyze the protein sequences from TCM. According to combination of in silico proteolysis and molecular simulation, the biological activities of oligopeptides could be predicted rapidly based on the known TCM protein sequence. It might provide the methodology basis for rapidly and efficiently implementing the mechanism analysis of TCM oligopeptides.

Asunto(s)

RESUMEN

Synergistic effect is main pharmacological mechanism of traditional Chinese medicine(TCM). The research method based on the key targets combination is an important method to explore the synergistic effect of TCM. Peptide transporter 1 (PepT1) is an essential target for drug uptake into the bloodstream, accounting for about 50% of the total transporter protein content from the small intestine. Peroxisome proliferator-activated receptor α(PPARα) is the lipid-lowering target of fibrates, which have a good hypolipidemic effect by activating PPARα. It has been reported that PPARα could activate the gene expression of PepT1s, and PPARα agonists can promote the uptake of PepT1 substrates, indicating their synergistic effect. In this paper, PepT1 substrates and PPARα agonists from TCM were discovered, and their synergistic mechanism was also been discussed based on the target combination of PepT1 and PPARα. The support vector machine(SVM) model of PepT1 substrates was first constructed and utilized to predict potential TCM components. Meanwhile, merged pharmacophore and docking model of PPARα agonists was used to screen the potential active ingredients from TCM. According to the analysis results of two groups, the TCM combination of Panax notoginseng and Ganoderma lucidum, as well as TCM combination of P. notoginseng and Salvia miltiorrhiza were identified to have the synergistic mechanism based on target combination of PepT1 and PPARα. In this study, synergistic mechanism of TCM was analyzed for absorption and hypolipidemic effect based on target combination, which provides a new way to explore the synergetic mechanism of TCM related to pharmacokinetics.

Asunto(s)

RESUMEN

Gene-environment interactions that moderate aggressive behavior have been identified independently in the serotonin transporter (5-HTT) gene and monoamine oxidase A gene (MAOA). The aim of the present study was to investigate epistasis interactions between MAOA-variable number tandem repeat (VNTR), 5-HTTlinked polymorphism (LPR) and child abuse and the effects of these on aggressive tendencies in a group of otherwise healthy adolescents. A group of 546 Chinese male adolescents completed the Child Trauma Questionnaire and Youth self-report of the Child Behavior Checklist. Buccal cells were collected for DNA analysis. The effects of childhood abuse, MAOA-VNTR, 5-HTTLPR genotypes and their interactive gene-gene-environmental effects on aggressive behavior were analyzed using a linear regression model. The effect of child maltreatment was significant, and a three-way interaction among MAOA-VNTR, 5-HTTLPR and sexual abuse (SA) relating to aggressive behaviors was identified. Chinese male adolescents with high expression of the MAOA-VNTR allele and 5-HTTLPR "SS" genotype exhibited the highest aggression tendencies with an increase in SA during childhood. The findings reported support aggression being a complex behavior involving the synergistic effects of gene-gene-environment interactions.

RESUMEN

OBJECTIVE: To investigate the correlation between poststroke depression (PSD) and serum levels of inflammatory cytokines, neurologic impairment, daily life ability in patients with acute cerebral infarction at different time. METHODS: Two hundreds and eighty patients who admitted to our hospital with a diagnosis of acute infarction excluded the patients mismatch conditions were evaluated by Hamilton depres-sion rating scale (HDRS) to diagnose PSD respectively at admission and 3 months after stroke. Serum inflammatory cytokines high-sensitivity C-reactive protein(hs-CRP), tumor necrosis factor-α(TNF-α) and interleukin-6(IL-6) were determined. NIH stroke scale(NIHSS) and Barthel index for daily life ability were used to evaluate nerve functions. Then we analyzed the correlation between PSD and serum inflammatory cytokines, correlation between PSD and functional impairment and daily life ability at different time. Logistic regression was performed to ana-lyze the risk factors of PSD. RESULTS: The PSD incidence was higher in recovery stage than that in acute stage, but there was no difference. Serum inflammatory cytokines were higher in PSD group at admission than that in non-PSD group. The NIHSS score and Barthel index in PSD group were different from those in non-group at acute and recovery stage. The OR score was 1.765, 1.646, 1.817, 1.188 and 2.015 respec-tively to TNF-α, IL-6 and Barthel index in the acute phase and to NIHSS and Barthel index in recovery stage. CONCLUSIONS: The pathogenesis of PSD at different courses of stroke is not same. TNF-α, IL-6 and Barthel index are the independent risk factors of PSD in acute phase, so do NIHSS score and Barthel index in recovery period.

Asunto(s)