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Objective To investigate the association of 13 single nucleotide polymorphism(SNP)sites in 6 phalange-bone development related genes[fibroblast growth factor receptor 2(FGFR2),indian hedgehog signaling molecule(IHH),Msh homeobox 1(MSX1),Runx family transcription factor 2(RUNX2),SRY-box transcription factor 9(SOX9),Wnt family member 5A(WNT5A)]with human index-ring finger length ratio(2D∶4D).Methods Digital cameras were used to take frontal photographs of the hands of 731 college students(358 males and 373 females)in Ningxia,and image analysis software was used to mark anatomical points and measure finger lengths of index(2th)and ring(4th);genotyping of 13 SNP sites(rs1047057,rs755793,rs41258305,rs3731881,rs3100776,rs12532,rs3821949,rs45585135,rs3749863,rs1042667,rs12601701,rs1829556,rs3732750)for 6 genes by multiplex PCR;One-Way ANOVA or independent sample t-test indirectly assessed the association between 2D∶4D and 13 SNP sites.Results Both left and right hand 2D∶4D were significantly higher in females than males in Ningxia college students(all P<0.01);no statistically significant differences in genotype and allele frequencies of the 13 SNP sites among different sexes(all P>0.05);among different sexes,male left hand 2D∶4D was significantly associated with the genotype of SOX9 gene rs12601701 site(P<0.05)and right hand 2D∶4D was significantly associated with the genotype of WNT5A gene rs1829556 site(P<0.05);the female right hand 2D∶4D was significantly associated with the MSX1 gene rs12532(P<0.01)and rs3821949(P<0.05)sites genotypes.Conclusion SOX9(rs12601701),WNT5A(rs1829556)and MSX1(rs12532 and rs3821949)gene polymorphisms may be associated with the formation of 2D∶4D in Ningxia population.
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Manganese superoxide dismutase catalyzes the dismutation of two molecules of superoxide radicals to one molecule of oxygen and one molecule of hydrogen peroxide. The oxidation of superoxide anion to oxygen by Mn3+SOD proceeds at a rate close to diffusion. The reduction of superoxide anion to hydrogen peroxide by Mn2+SOD can be progressed parallelly in either a fast or a slow cycle pathway. In the slow cycle pathway, Mn2+SOD forms a product inhibitory complex with superoxide anion, which is protonated and then slowly releases hydrogen peroxide out. In the fast cycle pathway, superoxide anion is directly converted into product hydrogen peroxide by Mn2+SOD, which facilitates the revival and turnover of the enzyme. We proposed for the first time that temperature is a key factor that regulates MnSOD into the slow- or fast-cycle catalytic pathway. Normally, the Mn2+ rest in the pent-coordinated state with four amino acid residues (His26, His74, His163 and Asp159) and one water (WAT1) in the active center of MnSOD. The sixth coordinate position on Mn (orange arrow) is open for water (WAT2, green) or O2• to coordinate. With the cold contraction in the active site as temperature decreases, WAT2 is closer to Mn, which may spatially interfere with the entrance of O2• into the inner sphere, and avoid O2•/Mn2+ coordination to reduce product inhibition. Low temperature compels the reaction into the faster outer sphere pathway, resulting in a higher gating ratio for the fast-cycle pathway. As the temperature increases in the physiological temperature range, the slow cycle becomes the mainstream of the whole catalytic reaction, so the increasing temperature in the physiological range inhibits the activity of the enzyme. The biphasic enzymatic kinetic properties of manganese superoxide dismutase can be rationalized by a temperature-dependent coordination model of the conserved active center of the enzyme. When the temperature decreases, a water molecule (or OH-) is close to or even coordinates Mn, which can interfere with the formation of product inhibition. So, the enzymatic reaction occurs mainly in the fast cycle pathway at a lower temperature. Finally, we describe the several chemical modifications of the enzyme, indicating that manganese superoxide dismutase can be rapidly regulated in many patterns (allosteric regulation and chemical modification). These regulatory modulations can rapidly and directly change the activation of the enzyme, and then regulate the balance and fluxes of superoxide anion and hydrogen peroxide in cells. We try to provide a new theory to reveal the physiological role of manganese superoxide dismutase and reactive oxygen species.
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Objective To investigate the association between the index finger and ring finger length ratio (2D ∶ 4D) and of four loci (rs6461992‚ rs6968828‚ rs7801581‚ rs17427875) polymorphism of homeobox (HOX) A11 gene among Ningxia college students. Methods Digit camera was used to collect frontal hand photos of 667 Han college students (348 males and 319 females) from Ningxia province; Image analysis software was used to mark the anatomical points and measure finger lengths of the index and ring fingers of both hands; multiplex PCR was used to detect each locus polymorphisms of HOXA11 gene; statistical software was used to compare and analyze the differences and associations of 2D ∶4D and gene polymorphisms between different genders. Results Among Ningxia Han college students‚ both left hand and right hand 2D ∶ 4D were significantly higher in females than those of in males (all P< 0. 05)‚ and there were no significant sex differences in right-left hand 2D ∶4D; the genotypes and allele frequencies of rs7801581 locus of HOXA11 gene differed significantly between genders (all P < 0. 05)‚ and none of the other locus polymorphisms showed any significant sex differences; only female left hand 2D ∶4D was significantly associated with rs6461992 locus genotype in the relationship between 2D ∶4D and HOXA11 polymorphisms (P<0. 05). Conclusion There were significant sex differences in 2D ∶ 4D among Han college students in Ningxia‚ and the rs6461992 locus polymorphism of HOXA11 gene may be associated with the formation of 2D ∶4D in females.
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Objective @#To investigate the clinical efficacy and application value of an improved 3D-printed guide plate for the treatment of primary trigeminal neuralgia (PTN) by percutaneous microballoon compression (PMC). @*Methods @# This prospective study included 42 patients with primary trigeminal neuralgia treated at the Department of Stomatology, Xuzhou Central Hospital, from September 2019 to January 2022. The group was divided by the random number table method into the experimental group (adopting 3D printing technology to make guide plates to guide the puncture, 22 cases) and the control group (adopting the traditional Hartel anterior approach to position the puncture, 20 cases). The intraoperative success rate of the first puncture, puncture time, operative time, radiation exposure of patients and postoperative complications were compared between the two groups. Postoperative Barrow Neurological Institute Scale (BNI) scores, facial numbness, diminished corneal reflexes and chewing weakness were recorded. The t-test, rank-sum test and chi-square test were used for statistical analysis, with P<0.05 indicating a statistically significant difference. @*Results @#The experimental group was significantly better than the control group in terms of the success rate of the first puncture (χ2 = 21.51, P<0.001), puncture time (Z = -5.51, P<0.001), operative time (t = 9.37, P<0.001), and the number of C-arm scans (Z = -4.59, P<0.001). Postoperative BNI scores of the experimental group included 21 cases of grade Ⅰ (91.5%) and 1 case of grade Ⅱ, while the control group included 17 cases of grade Ⅰ (85.0%), 2 cases of grade Ⅱ (10.0%) and 1 case of grade Ⅲ (5.0%), with no statistical significance (P>0.05). In the experimental group, 16 patients had postoperative masseter weakness, 1 had keratitis and 10 had perilabial herpes, while in the control group, 18 patients had postoperative masseter weakness, 2 had keratitis, 11 had perilabial herpes and 1 had monocular blindness. There was no significant difference in postoperative complications between the two groups (P>0.05). At 12 months of follow-up, there was no recurrence in either the experimental or control group. @* Conclusions @#3D digital guide plate-guided percutaneous microballoon compression for primary trigeminal neuralgia can improve the accuracy and safety of puncture to a certain extent, obviously shorten the operation time, reduce radiation exposure of the patients, improve the success rate of the operation, meaning it has a high clinical application value.
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Epilepsy is a chronic nervous system disease, which affects more than 70 million people all over the world. Although more than 30 kinds of antiepileptic drugs (AEDs) have been on the market, about one third of the patients with epilepsy fail to respond to medical treatment, who become drug-resistant epilepsy patients. Identifying the mechanism and developing effective treatment methods for drug-resistant epilepsy have become a hot area in the field of epilepsy research. This review discussed resent advance on the pathogenesis of drug-resistant epilepsy from the transporter hypothesis, neural network hypothesis and target hypothesis, and we also summarized the existing potential treatment methods and research progress of drug-resistant epilepsy, such as surgical resection, deep brain stimulation, ketogenic diet, precise treatment, and traditional Chinese medicine treatment. Our review may provide useful clues for the mechanisms research and clinical treatments of drug-resistant epilepsy.
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Objective To investigate the relationship between digit ratio and schizophrenia in men from Ningxia Han nationality. Methods Using anthropometry, digital camera was used to obtain finger photographs of both hands of 216 male subjects (nonnal control; 116, schizophrenia patient; 100). The anatomical points were marked and the length of each finger of both hands were measured by computer image analysis software (Image-Pro Plus 6 . 0 ) . Differences of the mean digit ratio of left and right hand 2D:3D, 2D:4D, 2D:5D, 3D:4D, 3D:5D, 4D:5D between the control group and the patient group were compared. The correlation between 2D :4D and onset age in the patient group were analyzed. Results Except for left and right hand 3D :4D, digit ratios in patient group were significantly higher than those in control group (2D :4D and 3D :5D in both hands, right hand 3D :5D, p all0. 05). Conclusion Digit ratio is related to the occurrence of schizophrenia in Ningxia Han male.
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Objective To investigate the association between 8 single-nucleotide polymorphisms (SNPs) of hydroxysteroid dehydrogenase (HSD) gene family and human digit ratio (2D ∶ 4D). Methods Randomly selected 808 college students (400 males and 408 females) as subjects, the digit ratio of left and right fingers were measured and calculated using computer image software. Eight SNPs (rs1000283, rs2236903, rs5479, rs56303414, rs676387, rs4445895, rs2066474, rs8190478) in HSD11B and HSD17B gene families were genotyped by multiplex PCR. The association between 2D ∶4D and different genotypes was analyzed by One-Way ANOVA. Results Female left hand(L)2D ∶ 3D, L2D ∶4D, L3D ∶4D, right hand(R)2D ∶4D, R2D ∶5D were significantly higher than male (P0. 05). The genotypes frequency of the 8 SNPs were not significantly associated with digit ratio (2D ∶4D) in both males and females (P>0. 05). Conclusion There are significant gender differences in digit ratio in Ningxia Han college students, but there is no correlation between digit ratio and 8 SNPs in HSD11B and HSD17B gene families, suggesting that HSD11B and HSD17B gene families may have nothing to do with the formation of human digit ratio.
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Objective@#The study aims to determine the latent class of roles in bullying victimization and perpetration among primary and secondary school students and to explore its relationship with academic achievement and screen use, to provide a reference for developing preventive measures and intervention plans.@*Methods@#A total of 29 099 students at grade 5,6,7,8,10, and 11 from Shenzhen were surveyed through convenient cluster sampling method by Olweus Bully/Victim Questionnaire. The latent class analysis was used for classifying bully/victim category.@*Results@#The latent class analysis revealed three classes, the noninvolvement group (low response rate at all items, 80.9%), the bullying victimization group (low response rate at bullying and high response rate at victimization items, 15.9%), and the bullying victimization and perpetration group (high response rate at all items,3.3%). Boys were more likely than girls to belong to the bullying victimization and perpetration at all study sections ( OR =0.83,0.74, 0.47 , P <0.05). Transfer students were at higher risk to be in the bullying victimization group in elementary and middle school ( OR = 1.21 ,1.21), while they were more likely to fall into the bullying victimization and perpetration group in high school ( OR =2.65)( P < 0.05). Students with poor academic performance were more likely to be in the bullying victimization group at all sections ( OR = 0.98 ,0.98,0.98) and in the bullying victimization and perpetration group at elementary and middle school ( OR =0.97, 0.98)( P < 0.05 ). Students spending longer time on screen had elevated risk in the bullying victimization group ( OR =1.06,1.04,1.08, P < 0.05 ).@*Conclusion@#Students with poor academic achievement and prolonged screen time are at higher risks to be involved in bullying victimization and perpetration. Collaboration between home and school are needed to preventing bullying victimization perpetration.
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Objective @# investigate the correlation between the ossification of the styloid hyoid ligament and Bell’s facial paralysis and provide a reference for clinical diagnosis and treatment.@* Methods@# A case of ossification of the bilateral stylohyoid ligament with Bell's facial palsy caused by ossification of the bilateral stylohyoid ligament was diagnosed by clinical manifestations, differential diagnosis and imaging examination. The surgical plan was determined, and combined surgical resection of the ossified area of the styloid hyoid ligament and the greater horn of the hyoid was performed. Postoperative cefoxitin sodium anti-inflammatory treatment, methylprednisolone hormone treatment, acyclovir antiviral treatment, mecobalamin nutritional neurotherapy, and the relevant literature were analyzed. @* Results@# The patient experienced pain when swallowing before surgery, disappearance of right frontal ridges, incomplete eyelid closure, and ptosis of mouth corners. An MRI scan of the brain excluded intracranial space-occupying lesions and resulted in the diagnosis of Bell’s facial paralysis. High-resolution CT of the styloid process confirmed ossification of the styloid hyoid ligament. Styloid process shortening and partial hyoid resection were performed under general anesthesia. Half a month after discharge, the symptoms of sore throat and pain in swallowing disappeared, facial nerve function recovered well, right eyelid closure function recovered well, and right mouth droop improved. The facial nerve function basically returned to normal after 1 month of follow-up. A review of the relevant literature showed that ossification of the stylohyoid ligament to form pseudojoint dilation can locally stimulate the peripheral facial nerve and lead to facial paralysis symptoms. @*Conclusion@# Ossification of the styloid hyoid ligament is usually characterized by pharyngeal pain, which can be confirmed by imaging examination. Ossification of the styloid hyoid ligament with facial paralysis is rare in the clinic, so it is necessary to make a clear diagnosis and treat the symptoms.
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@#Glass ionomer cement (GIC) is widely used as a common filling material in dentistry but still exhibits problems with secondary caries and fractures. Thus, the antibacterial and anti-caries performance of GIC needs to be further improved. In recent years, natural antimicrobial components have become more desirable due to their good biological properties and low drug resistance. In this review, the natural antimicrobial ingredients in GIC modification are classified, reviewed and summarized according to the different sources of antimicrobial ingredients. In terms of animal origin, chitosan and casein phosphopeptide-amorphous calcium phosphate exhibit antimicrobial properties without affecting the mechanical properties of materials; propolis and bioactive enzymes have good biocompatibility; in terms of plant origin, polyphenols help improve the antimicrobial and mechanical properties of the material; arginine has a good remineralization effect; and plant essential oils have a certain ion release effect. In terms of microbial origin, antibiotics greatly improve the antibacterial properties of materials; in addition, the combined application of natural antimicrobial ingredients also exhibited excellent performance. Despite these advantages, the optimal addition concentration and biocompatibility in vivo are questions that need to be further explored before clinical applications can be achieved.
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Wnt/β-catenin signaling pathway plays an important role in the proliferation, growth, invasion, and metastasis of human cancers. Moreover, β-catenin/T-cell factor 4 (TCF4) interaction regulates the transcription of the key oncogenes in Wnt/β-catenin signaling pathway. Therefore, β-catenin/TCF4 interaction would be a promising therapeutic target for the development of highly selective anticancer agents. At present, most ongoing small-molecule inhibitors targeting β-catenin/TCF4 interaction, including PKF222-815, iCRT3/5/14, LF3, and sanguinarine, have been developed in preclinical studies for human cancer therapeutics. In this review, we summarized the research advances of up-to date inhibitors targeting β-catenin/TCF4 interaction, including the molecular structure and cellular functions of β-catenin in canonical Wnt signaling pathway. This review holds a hopeful avenue for the development of novel and highly selective Wnt inhibitors targeting β-catenin/TCF4 interaction for future anticancer strategy.
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To develop a fluorescence polarization (FP)-based high-throughput screening (HTS) assay to identify novel small-molecule antagonists targeting β-catenin/TCF4 (T-cell factor 4) interaction, recombinant human β-catenin was expressed in Escherichia coli Rosetta (DE3) cells and purified by HisTrapTM column. The bioactivity of purified β-catenin was further analyzed by enzyme-linked immunosorbent assay (ELISA). According to FP principle, the β-catenin/TCF4 binding model was performed, and fluorescence isothiocyanate (FITC) labeled TCF4 peptide (FITC-TCF4) served as the molecular probe of adaptor for binding to β-catenin. The FITC-TCF4 and β-catenin working concentration were optimized, and the binding conditions (complex stability and dimethylsulfoxide (DMSO) tolerance) have been investigated yet for further hits screening. The results showed that recombinant human β-catenin was successfully expressed and purified β-catenin exhibited favorable bioactivity in ELISA binding assay. Subsequently, the FP-based HTS assay was performed using 20 nmol·L-1 FITC-TCF4 and 100 nmol·L-1 β-catenin. Under these optimized conditions, a high Z´factor of 0.88 was achieved in a 384-well format and this FP-based HTS assay was very stable with regard to DMSO. Through screening of a natural-based product library (NBPL) using the established FP-based HTS assay, three hits (sanguinarine, chelerythrine, and compound S720) were identified as potential β-catenin/TCF4 interaction antagonists. Taken together, we have successfully developed a simple, robust and reliable FP-based HTS assay for screening of novel antagonists targeting β-catenin/TCF4 interaction.
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Objective To investigate the efficacy of neutralizing antibodies induced by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) receptor-binding domain (RBD) and spike (S) protein S1 subunit. Methods The SARS-CoV-2 RBD and mouse immunoglobulin G1 (IgG1) Fc fragment (mFc) fusion protein expression plasmid pVRCRBD- mFc was constructed and transfected into human embryonic kidney 293T cells. The RBD-mFc fusion protein in the cell supernatants was detected by Western blotting. The effect of RBD-mFc in cell supernatants and CHO recombinant S1-human IgG1 Fc (S1-hFc) fusion protein on SARS-CoV-2 infection was detected by microneutralization test. BALB/c mice were immunized with plasmid pVRC-RBD-mFc and S1-hFc fusion protein via intramuscular injection. Anti-S1 IgG antibodies in mouse sera were detected by enzyme-linked immunosorbent assay (ELISA), and the virus neutralization activity of mouse sera was detected by microneutralization test. Results The RBD-mFc fusion protein could be detected in the culture supernatants of 293T cells transfected with the plasmid pVRC-RBD-mFc, the concentrated supernatants and the S1- hFc fusion protein could inhibit SARS-CoV-2 infection on Vero E6 cells in a concentration-dependent manner. Anti-S1 IgG antibodies could be detected in the sera of mice immunized with plasmid pVRC-RBD-mFc and S1-hFc fusion protein, and the sera of both groups could neutralize SARS-CoV-2 infection. The serum antibody titers and virus neutralization activity of S1- hFc fusion protein immunized mice were significantly higher than those of plasmid pVRC-RBD-mFc immunized mice (both P<0.01). Conclusion Both SARS-CoV-2 RBD and S1 subunit may be used as effective vaccine antigens. Compared with DNA vaccine, recombinant subunit vaccine can induce neutralizing antibody more effectively..
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OBJECTIVE: To compare dorsal-and-medial hybrid approach and medial-to-lateral approach in laparoscopic right hemicolectomy with complete mesocolic excision(CME). METHODS: Patients undergone laparoscopic right hemicolectomy in Department of Gastrointestinal Surgery in Ruijin Hospital Affiliated to Shanghai Jiaotong University School of Medicine from July 2017 to April 2018 were prospectively included.Patients were divided into two groups:dorsal group and medial group. Clinical and pathological data were collected and compared between the two groups. RESULTS: There were 35 patients in medial group and 40 patients in dorsal group. No significant differences were found between the two groups in baseline characteristics,perioperative outcomes and pathological results. No significant difference was found between the two groups in length of bowel(24 cm vs. 22 cm),A line distance(9.8 cm vs.9.4 cm),B line distance(9.0 cm vs. 8.5 cm),area of mesentery(112.4 cm~2 vs. 109.0 cm~2),total lymph node count(19 vs.19),lymph node adequate ratio(97.1% vs. 97.5%)and CME ratio(80% vs. 85%). Obesity was found to be an independent risk factor of CME ratio(P=0.019). CONCLUSION: Dorsal-and-medial hybrid approach and medial-to-lateral approach are comparable in safety,feasibility and effectiveness in laparoscopic right hemicolectomy with complete mesocolic excision. Randomized clinical trials with larger sample size are needed.
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Objective@#To examine the longitudinal relationship between the prosocial behaviors and depressive symptoms in rural adolescents using a cross-lagged model,and to provide a reference for improving mental health of adolescents.@*Methods@#Participants were junior school 372 students in grade seven recruited from a rural school in Anhui province, who filled the Strengths and Difficulties Questionnaire (SDQ) and a short version of Center for Epidemiological Survey Depression Scale (CESD-10) three times (once a year for 2 years),and the cross lag model is established.@*Results@#Depressive symptoms(r=0.39-0.45) and prosocial behavior(r=0.43-0.46) of rural adolescents are relatively stable in junior middle school(P<0.01);The depression score of adolescents in grade 9 was higher than that in grade 7 and 8(P<0.05) and girls’ depression score was higher than boys’ (F=7.94,P<0.01).The relationships between prosocial behaviors(T1, T2, T3) and depressive symptoms(T1, T2, T3) were all negatively correlated in rural adolescents(r=-0.23~-0.13, P<0.05). Depressive symptoms in T1 and T2 could negatively predict prosocial behaviors in T2 and T3, respectively (β T1-T2=-0.10, β T2-T3=-0.11, P<0.05), while prosocial behaviors in T2 could negatively predicted depressive symptoms in T3 (β=-0.14, P<0.05).@*Conclusion@#During the three years of junior high school, the depressive symptoms of rural adolescents negatively predicted prosocial behavior, and from the second to the third year of junior high school, prosocial behavior negatively predicted depressive symptoms.Community health workers should pay more attention on depressive symptoms of rural adolescents, which could be prevented and improved through prosocial behavioral intervention, including helping and sharing.
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As a pathogen causing many infectious diseases, Flavivirus genus arborvirus has caused public health emergencies worldwide and posed a serious threat to human health. Attenuated vaccine is the most effective vaccine type against Flavivirus genus arborvirus. The attenuated vaccines against yellow fever virus and Japanese encephalitis virus obtained by consecutive cell passages play an important role in preventing viral infections. Recently, reverse genetics technique has been used to modify the flavivirus genome to obtain the attenuated phenotype, and this technique has made significant progress in the development of Flavivirus genus arbovirus vaccines. This review summarizes the history and the current status of attenuated vaccine of Flavivirus genus arborvirus.
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Objective: To compare the efficacy and safety between humidified high flow nasal cannula (HHFNC) and noninvasive positive pressure ventilation (NPPV) in patients with chronic obstructive pulmonary disease (COPD) complicated with type 2 respiratory failure after extubation. Methods: Seventy-two patients with COPD complicated with type 2 respiratory failure were enrolled after extubation and were randomized into HHFNC group and NPPV group at 1: 1 ratio, with 36 patients in each group. The blood gas analysis index, respiratory rate, heart rate, mean arterial pressure, reintubation rate, incidence of tracheotomy, intensive care unit stay, incidence of adverse events and mortality were compared between the two groups before treatment and 2, 12, 24 h after treatment. Results: The pH at 24 h, partial pressure of oxygen in artery (PaO2) at 2 h and 12 h, and oxygenation index (PaO2/FiO2) at 2 h and 12 h after treatment were significantly higher in the HHFNC group compared with the NPPV group (all P0.05), while the overall incidence of adverse events, intolerance rate, flatulence rate and aspiration rate were significantly lower in the HHFNC group than those in the NPPV group (all P 0.05). Conclusion: The short-time efficacy and safety of HHFNC are better than NPPV in treatment of COPD complicated with type 2 respiratory failure.
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Objective: To explore the regulation of p38 mitogen-activated protein kinase (MAPK) pathway by West Nile virus (WNV) in human neuroblastoma SH-SY5Y cells and the contributions of p38 MAPK to WNV replication as well as stress and inflammatory response related molecule expression. Methods: Total and phosphorylated p38 MAPK levels were analyzed in SH-SY5Y cells incubated with WNV for short (5, 15, 30 and 60 min) and long (12, 24, 48 and 60 h) durations by Western blotting. Dynamic changes of CCAAT/enhancer-binding protein homologous protein (CHOP), interleukin 6 (IL-6), activating transcription factor 6α (ATF6α) and interferon-stimulated gene 15 (ISG15) mRNA expression in WNV infected cells were detected by qRT-PCR. In response to WNV infection, WNV RNA level and CHOP, IL-6, ATF6α and ISG15 mRNA levels were assessed in SH-SY5Y cells transfected with p38 MAPK siRNA. Results: Incubation with WNV for short durations enhanced p38 MAPK phosphorylation compared to the untreated control. The p38 MAPK signaling pathway was activated at 12 h and 24 h in WNV-infected SH-SY5Y cells, but down-regulated at 48 h and 60 h. WNV infection led to increased mRNA expression of CHOP, IL-6 and ISG15 and reduced ATF6α mRNA. In comparison with control siRNA transfection, the levels of WNV RNA (P<0.05) and ATF6α mRNA (P<0.01) were increased and CHOP mRNA level was decreased (P<0.05) in WNV-infected SH-SY5Y cells with the p38 MAPK siRNA transfection. Conclusion: The p38 MAPK pathway is activated during early stage of WNV infection and such activation may negatively regulate WNV replication. WNV-induced stress response molecules CHOP and ATF6α and proinflammatory cytokine IL-6 production by SH-SY5Y cells are coupled with the regulation of p38 MAPK pathway.
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Objective To study the mechanism of the Hedgehog signaling transduction intervened by polypeptide extract from scorpion venom (PESV) on K562/BALB/c-nu leukemia mice. Trying to analyze the molecular mechanisms and targets of the inhibited effect of PESV on chronic myeloid leukemia (CML) in vivo. Methods After establishing the K562/BALB/c-nu leukemia mice successfully, the model mice were divided into six groups which were the blank group, the PESV high, medium, and low doses (0.3, 0.6, 1.2 mg/kg) group, the Imatinib (50 mg/kg) group, and the model group. After 14 d drug intervention, the levels of gene and protein expression of Hedgehog signaling pathway upstream factors Shh, Ptch, and Smo were detected by qRT-PCR and Western blotting, and the protein expression of downstream factor Gli1 was determined by ELISA test. Results Compared to the model group, the genetic and protein expression of Shh which was an upstream factor were increased in the PESV groups. The mRNA and protein expression of Ptch and Smo in PESV low-dose and medium-dose groups were decreased. There were no significant differences of upstream factors between Imatinib group and model group. The concentration of downstream Gli1 protein significantly decreased within low-dose and medium-dose PESV groups, while there was no significant difference between high-dose PESV group and Imatinib group. Conclusion PESV can inhibit the expression of Hedgehog signaling pathway upstream factor Ptch, Smo and downstream factor Gli1 on the mRNA and protein level, while Imatinib has no obvious inhibitory effect on the Hedgehog signaling pathway.
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OBJECTIVE@#To study the expression of SOX4 gene in patients with acute myeloid leukemia (AML) and its correlation with clinical features and prognosis, and to explore the role of this gene in acute myeloid leukemia.@*METHODS@#The real-time guantitative PCR was used to detect the expression level of SOX4 gene in bone marrow of 96 patients with newby diagmsed AML, and the features and prognosis was analyzed.@*RESULTS@#The level of SOX4 expression in the 96 AML patients was significantly higher than that in healthy controls (P0.05). In AML patients the SOX4 gene expression level did not significantly correlated with the white blood cell count, hemoglobin level, platelet count primitive cell count, reticulocyte count and other laboratory indexes ( P>0.05), while which correlated with the overall survival (OS) (P<0.01) and erent-free survival (EFS) (P<0.05).@*CONCLUSION@#The high expression of SOX4 gene affects the survival time of patients (OS, EFS), suggesting that may be one of the unfavorable prognostic factors for the AML patients.