BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the ...BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.展开更多
BACKGROUND Phosphoglycerate kinase 1(PGK1)has been identified as a possible biomarker for breast cancer(BC)and may play a role in the development and advancement of triple-negative BC(TNBC).AIM To explore the PGK1 and...BACKGROUND Phosphoglycerate kinase 1(PGK1)has been identified as a possible biomarker for breast cancer(BC)and may play a role in the development and advancement of triple-negative BC(TNBC).AIM To explore the PGK1 and BC research status and PGK1 expression and mecha-nism differences among TNBC,non-TNBC,and normal breast tissue.METHODS PGK1 and BC related literature was downloaded from Web of Science Core Co-llection Core Collection.Publication counts,key-word frequency,cooperation networks,and theme trends were analyzed.Normal breast,TNBC,and non-TNBC mRNA data were gathered,and differentially expressed genes obtained.Area under the summary receiver operating characteristic curves,sensitivity and specificity of PGK1 expression were determined.Kaplan Meier revealed PGK1’s prognostic implication.PGK1 co-expressed genes were explored,and Gene Onto-logy,Kyoto Encyclopedia of Genes and Genomes,and Disease Ontology applied.Protein-protein interaction networks were constructed.Hub genes identified.RESULTS PGK1 and BC related publications have surged since 2020,with China leading the way.The most frequent keyword was“Expression”.Collaborative networks were found among co-citations,countries,institutions,and authors.PGK1 expression and BC progression were research hotspots,and PGK1 expression and BC survival were research frontiers.In 16 TNBC vs non-cancerous breast and 15 TNBC vs non-TNBC datasets,PGK1 mRNA levels were higher in 1159 TNBC than 1205 non-cancerous breast cases[standardized mean differences(SMD):0.85,95%confidence interval(95%CI):0.54-1.16,I²=86%,P<0.001].PGK1 expression was higher in 1520 TNBC than 7072 non-TNBC cases(SMD:0.25,95%CI:0.03-0.47,I²=91%,P=0.02).Recurrence free survival was lower in PGK1-high-expression than PGK1-low-expression group(hazard ratio:1.282,P=0.023).PGK1 co-expressed genes were concentrated in ATP metabolic process,HIF-1 signaling,and glycolysis/gluconeogenesis pathways.CONCLUSION PGK1 expression is a research hotspot and frontier direction in the BC field.PGK1 may play a strong role in promoting cancer in TNBC by mediating metabolism and HIF-1 signaling pathways.展开更多
AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance.METHODS: Thirteen physically active male college students were divided into two...AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance.METHODS: Thirteen physically active male college students were divided into two groups (AG or placebo)and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk.They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover,the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise,immediately after exercise, and 20, 40, 60, and 120 min after exercise.RESULTS: The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen.CONCLUSION: Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.展开更多
Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis.In the present retrospective case-control study,we included 582 pa...Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis.In the present retrospective case-control study,we included 582 patients with amyotrophic lateral sclerosis and 582 age-and sexmatched healthy controls.All amyotrophic lateral sclerosis participants received treatment in the Department of Neurology,West China Hospital,China,between May 2008 and December 2018.Serum creatine kinase levels in patients with amyotrophic lateral sclerosis were significantly higher than those in healthy controls.Subgroup analysis revealed that serum creatine kinase levels in men were higher than those in women in both amyotrophic lateral sclerosis patients and healthy controls.Compared with patients with bulbar-onset amyotrophic lateral sclerosis,patients with limb-onset amyotrophic lateral sclerosis had higher creatine kinase levels.Spearman's correlation analysis revealed that serum creatine kinase levels were not correlated with body mass index,Amyotrophic lateral Sclerosis Functional Rating ScaleRevised score,or progression rate.After adjusting for prognostic covariates,higher log creatine kinase values were correlated with higher overall survival in the amyotrophic lateral sclerosis patients.We also investigated the longitudinal changes in serum creatine kinase levels in 81 amyotrophic lateral sclerosis patients;serum creatine kinase levels were decreased at the second blood test,which was sampled at least 6 months after the first blood test.Together,our results suggest that serum creatine kinase levels can be used as an independent factor for predicting the prognosis of amyotrophic lateral sclerosis patients.This study received ethical approval from the Ethics Committee of West China Hospital,China(approval No.2015(236))on December 23,2015.展开更多
Mitogen activated-protein kinases (MAPKs) are important components in signal transduction pathways responding to various biotic and abiotic stresses. An MAPK gene, OsMPK14 (GenBank Accession No. GQ265780) from ri...Mitogen activated-protein kinases (MAPKs) are important components in signal transduction pathways responding to various biotic and abiotic stresses. An MAPK gene, OsMPK14 (GenBank Accession No. GQ265780) from rice (Oryza sativa L.), was cloned by RT-PCR. The full-length cDNA of OsMPK14 consists of 1660 bp in size, containing an open reading frame of 1629 bp, which encodes a 542-amino-acid polypeptide and has a typical protein kinase domain and a phosphorylation activation motif TDY. Sequence alignment and analysis revealed that OsMPK14 was located on rice chromosome 5, and composed of nine exons and eight introns in the coding region. Semi-quantitative RT-PCR was performed to detect the expression patterns of OsMPK14 in rice shoots and roots under darkness, drought, high salinity, low temperature and abscisic acid treatments. The OsMPK14 mRNA was induced by abscisic acid, low temperature and high salinity, but weakly inhibited by drought. In addition, the expression of OsMPK14 was up-regulated in roots, but down-regulated in shoots by light. The results indicate that OsMPK14 could be implicated in diverse rice stimuli-responsive signaling cascades, and its expression might be regulated by multiple factors.展开更多
Summary: The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athle...Summary: The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athletes were divided into 4 groups: group A (supplementation of Cr alone), group B (supplementation of oligosaccharide), group C (supplementation of oligosaccharide and Cr) and group D (placebo control group). By using orthogonal L4 table (2a ), the experiment was performed. There were factors including oligosaccharide (carbohydrate, CHO), Cr and their correlation. Each factor had two levels: supplementation and no-supplementation. The results showed that the supplementation of CliO or Cr alone, combined supplementation of CHO and Cr could significantly reduce the glucose, urea nitrogen levels in blood and serum CK activity after competition in the athletes. Moreover, the effects of combined supplementation of CHO and Cr were more satisfactory. It was concluded that supplementation of CliO and Cr could promote the recovery of physical performance and athletic abilities after athletics in basketball athletes.展开更多
BACKGROUND: Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects...BACKGROUND: Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE: To investigate the neuroprotective effects of flunarizine (FNZ), lamotrigine (LTG) and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING: This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People's Hospital, Guangdong Medical College. MATERIALS: Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ + LTG, and model groups, with 10 rats in each group. METHODS: Rats in the FNZ, LTG, and FNZ + LTG groups received intragastric injections of FNZ (0.5 mg/kg/d), LTG (10 mg/kg/d), and FNZ (0.5 mg/kg/d) + LTG (10 mg/kg/d), respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES: Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS: Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ + LTG groups following ischemia, compared with the model group (P 〈 0.01). However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ + LTG group, following ischemia (P 〈 0.01). CONCLUSION: Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.展开更多
Objective To study the differential diagnosis on cerebral concussion and mild cerebral contusion value of the brain type creatine kinase isoenzyme(CK BB),and evaluate the seriousness of brain damage and prognosis of t...Objective To study the differential diagnosis on cerebral concussion and mild cerebral contusion value of the brain type creatine kinase isoenzyme(CK BB),and evaluate the seriousness of brain damage and prognosis of the patients with acute head injury.Methods Chromatographic separating and fluorometric quantifying technique was used to detect the CK BB activity in the cerebrospinal fluid(CSF) of 117 patients with acute head injury and 12 patients with increased intracranial pressure and 20 normal people.Results The CSF CK BB activity of the patients with acute head injury was remarkably higher than that of the normal people and the CSF CK BB activity increased with the seriousness of brain damage.There was a close relationship between CSF CK BB activity and prognosis,and higher activity of CSF CK BB indicated poor prognosis.Conclusion CSF CK BB activity could be used as a new index to diagnose brain damage and evaluate the seriousness of brain damage and prognosis.展开更多
Objective To observe the relationship between serum creatine kinase isoenzyme MM sub-bands (CKMM3/MM1 ratio) and the gradation of coronary stenosis and provide a simple, reliable, and economical method for identifying...Objective To observe the relationship between serum creatine kinase isoenzyme MM sub-bands (CKMM3/MM1 ratio) and the gradation of coronary stenosis and provide a simple, reliable, and economical method for identifying high-risk unstable angina pectoris (UAP). Mehtods Blood samples were drawn at different time after onset of chest pain in 21 patients with UAP and only once in 20 each volunteers for control. CKMM3/MM1 ratio was detected by nonserial buffer agarose gel electrophoresis. CKMB and CK were observed by velocity method. An emergent coronary arteriography was performed as soon as patients were admitted into hospital. Results Patients with UAP were divided into two subgroups: patients with elevated serum enzyme [P( + )] and patients with normal serum enzyme [P( - ) ] according to CKMM3/MM1 ratio < 0. 5. Patients with UAP( + ) had higher serum CKMM3/MM1 ratios from 0.5 to 12hrs and serum CKMB from 2 to 12 hrs than those with UAP( - ) and control ( P < 0. 05) . Serum enzyme concentrations of patients with UAP whose coronary lumen had 90% or more than 90% stenosis were significantly higher than those whose coronary lumen had less than 90% stenosis ( P <0. 01) . Any CK-MM3/MM1 ratio was less than 1. 0 and CK within the normal range in patients with UAP( + ) group. Conclusions CKMM3/MM1 ratios in patients with UAP can reflect severity of myocardial ischemia. SerumCKMM3/MM1 ratio provides a simple, reliable, and economical method for identifying high-risk UAP.展开更多
Objective:To assess the correlation of signs of myocardial damage to serum cardiac troponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated ne...Objective:To assess the correlation of signs of myocardial damage to serum cardiac troponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated neonates and 25 controls at 12 h of age by immunoassay.The asphyxiated neonates were followed up until discharge or death.Results:Asphyxiated neonates had significantly higher concentrations of cTnI and CK-MB than controls(P<0.001).Serum cTnI concentrations were significantly higher in asphyxiated neonates who developed hypotension,heart failure or those had low ejection fraction(P<0.01).Serum cTnI concentrations were significantly higher in asphyxiated who died than those who survived(P<0.01).There was no significant difference in serum CK-MB mass concentrations between asphyxiated neonates with and without these complications.Conclusion:Unlike CK-MB,serum cTnI concentrations are significantly higher in asphyxiated neonates who died or developed cardiac dysfunction.展开更多
SNF1-related protein kinase 2(SnRK2)family members are essential components of the plant abscisic acid(ABA)signaling pathway initiated by osmotic stress and triggering a drought stress response.This study characterize...SNF1-related protein kinase 2(SnRK2)family members are essential components of the plant abscisic acid(ABA)signaling pathway initiated by osmotic stress and triggering a drought stress response.This study characterized the molecular properties of TaSnRK2.4 and its function in mediating adaptation to drought in Triticum aestivum.Transcripts of TaSnRK2.4 were upregulated upon drought and ABA signaling and associated with drought-and ABA-responsive cis-elements ABRE and DRE,and MYB and MYC binding sites in the promoter as indicated by reporter GUS protein staining and activity driven by truncations of the promoter.Yeast two-hybrid,BiFC,and Co-IP assays indicated that TaSnRK2.4 protein interacts with TaPP2C01 and an ABF transcription factor(TF)TaABF2.The results suggested that TaSnRK2.4 forms a functional TaPP2C01-TaSnRK2.4-TaABF2 module with its upstream and downstream partners.Transgene analysis revealed that TaSnRK2.4 and TaABF2 positively regulate drought tolerance whereas TaPP2C01 acts negatively by modulating stomatal movement,osmotic adjustment,reactive oxygen species(ROS)homeostasis,and root morphology.Expression analysis,yeast one-hybrid,and transcriptional activation assays indicated that several osmotic stress-responsive genes,including TaSLAC1-4,TaP5CS3,TaSOD5,TaCAT1,and TaPIN4,are regulated by TaABF2.Transgene analysis verified their functions in positively regulating stomatal movement(TaSLAC1-4),proline accumulation(TaP5CS3),SOD activity(TaSOD5),CAT activity(TaCAT1),and root morphology(TaPIN4).There were high correlations between plant biomass and yield with module transcripts in a wheat variety panel cultivated under drought conditions in the field.Our findings provide insights into understanding plant drought response underlying the SnRK2 signaling pathway in common wheat.展开更多
AIM To detect the expression of Raf kinase inhibitory protein(RKIP) in gastrointestinal stromal tumors(GISTs) and to analyze its relationship with clinicopatholgical characteristics and prognosis of this disease.METHO...AIM To detect the expression of Raf kinase inhibitory protein(RKIP) in gastrointestinal stromal tumors(GISTs) and to analyze its relationship with clinicopatholgical characteristics and prognosis of this disease.METHODS Sixty-three patients with pathologically diagnosed GISTs who underwent surgical resection at the Shengjing Hospital of China Medical University from January 2011 to January 2015 and had complete clinical,pathological,and follow-up data were included. Immunohistochemical method was used to detect the expression of RKIP in GIST tissue samples from these patients. KaplanMeier method was used to calculate the survival rate of 60 patients with complete follow-up data,and Cox regression analysis was performed to identify factors affecting the prognosis of patients GISTs to evaluate further the diagnostic and prognostic value of RKIP in GISTs.RESULTS In GIST tissues,RKIP positive signals,manifesting as brownish yellow or brown granules,were located in the cytoplasm or on the membrane. Of 63 tissue samplesincluded in this study,34(54%) were positive and 29(46%) were negative for RKIP expression. Statistical analysis showed that RKIP expression in GISTs was significantly associated with tumor size,National Institutes of Health(NIH) risk grade,and mucosal invasion,but had no significant association with age,gender,tumor location,or the number of mitotic figures. Univariate Kaplan-Meier analysis revealed that the 1-,3-,and 5-year survival rates were 94.4%,89.2%,and 80.5% for patients with positive RKIP expression,and 88.6%,68.2%,and 48.2% for patients with negative RKIP expression,suggesting that patients with high RKIP expression had significantly higher survival rates than those with low expression(Log-rank test,P = 0.0015). Cox regression analysis demonstrated that NIH risk grade was significantly associated with the prognosis of GISTs(P = 0.037),suggesting that NIH risk grade is a significant predictor of the prognosis of GISTs. RKIP expression had a tendency to predict the survival of GISTs(P = 0.122),suggesting that RKIP expression may have appreciated value to predict the prognosis of GISTs.CONCLUSION This study demonstrated that:(1) RKIP expression in GISTs is associated with tumor size,NIH risk grade,and mucosal invasion,and low or no expression of RKIP predicts a high malignancy potential;(2) high RKIP correlates positively with the survival of patients with GISTs; and(3) RKIP expression has appreciated value for predicting the survival of patients with GISTs,although it is not an independent prognostic factor in GISTs.展开更多
Resistance gene analog(RGA) screening of mapped disease-resistant genes not only helps to clone these genes but also helps to develop efficient molecular markers for resistance breeding. The present study focused on t...Resistance gene analog(RGA) screening of mapped disease-resistant genes not only helps to clone these genes but also helps to develop efficient molecular markers for resistance breeding. The present study focused on the PmU region located on chromosome 7 Au L of Triticum urartu, and recently, a nucleotide binding site(NBS)-encoding gene, Pm60, was cloned from the same chromosome arm. In this research, NBS, protein kinase(PK), and ATP-binding cassette(ABC), the three disease resistance-related gene families, were analyzed within PmU region by using informatics tools, and an expression experiment was conducted to verify their functions in vivo. Comparative genomic analysis revealed that 126 RGAs were included on chromosome 7 Au L, and 30 of the RGAs as well as Pm60 were found in the Pm U region. Transcriptome database analysis of T. urartu revealed 14 PmU-RGAs with expression data, and three PmU-NBSs exhibited significant changes in expression after inoculation with Blumeria graminis f. sp. tritici(Bgt); TRIUR314879 was up-regulated, while TRIUR300450 and TRIUR306270 were down-regulated. Cluster analysis showed that these three PmU-NBSs were clustered far from the cloned wheat resistance genes. Then, qRT-PCR was performed to investigate the expression of 14 PmU-RGAs and Pm60 after inoculation with Bgt race E09; the results showed that Pm60 was specifically expressed in UR206 which carrying PmU, but not in susceptible UR203; while TRIUR314879 was significantly up-regulated and TRIUR300450 was downregulated in UR206 after inoculation. These results indicated that PmU is Pm60, and TRIUR314879 and TRIUR300450 may also be involved in the defense against Bgt.展开更多
AIM: To elucidate the role of overexpressed polo-like kinasel (PLK1)in hepatocellular carcinoma (HCC). METHODS: We prospectively collected clinicopathological, immunohistochemical and semi-quantitative reverse t...AIM: To elucidate the role of overexpressed polo-like kinasel (PLK1)in hepatocellular carcinoma (HCC). METHODS: We prospectively collected clinicopathological, immunohistochemical and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) data from 135 HCC patients undergoing successful hepatectomy. The correlations between PLK1 mRNA expression and clinicopathologic variables were analyzed by Mann-Whitney U test. Prognostic factors were identified by univariate and multivariate analyses. RESULTS: Immunohistochemical results showed overexpression of PLK1 was mainly found in tumor tissues compared with tumor-free tissue. A similar mRNA result was obtained by semi-quantitative RT-PCR. A total of 111 samples were positive for PLK1 mRNA expression. The positive expression was correlated with venous invasion, tumor nodules and Edmondson grade. Furthermore, 1, 3, 5-year survival rates in the positive expression group were significantly lower than the negative control group. Multivariate analysis showed that positive PLK1 expression was an independent risk factor for HCC. CONCLUSION: PLK1 could be a potential biomarker for diagnosis and therapy for HCC.展开更多
Wall-associated kinases(WAKs) play an important role in plant defense and development.Considerable progress has been made in understanding WAK genes in Arabidopsis thaliana.However, much less is known about these gene...Wall-associated kinases(WAKs) play an important role in plant defense and development.Considerable progress has been made in understanding WAK genes in Arabidopsis thaliana.However, much less is known about these genes in common wheat. Here, we isolated a novel wheat WAK gene TaWAK5 from sharp eyespot disease-resistant wheat line CI12633,based on a differentially-expressed sequence identified by microarray analysis. The transcript abundance of TaWAK5 was rapidly increased following inoculation with the pathogen Rhizoctonia cerealis. TaWAK5 in resistant wheat lines was induced to higher levels than in susceptible lines at 7 days post inoculation with R. cerealis. The expression of TaWAK5 was also induced by treatments with exogenous salicylic acid, abscisic acid, and methyl jasmonate. The deduced TaWAK5 protein contained a signal peptide, two epidermal growth factor(EGF)-like repeats, a transmembrane domain, and a serine/threonine protein kinase catalytic domain. Subcellular localization analyses in onion epidermal cells indicated that the TaWAK5 protein was localized to the plasma membrane. Virus-induced gene silencing of TaWAK5 in CI12633 plants showed that the silencing of TaWAK5 did not obviously impair wheat resistance to R. cerealis, suggesting that TaWAK5 may be not the major gene in wheat defense response to R. cerealis, or that it is functionally redundant with other genes. This study paves the way for further research into WAK functions in wheat stress physiology.展开更多
BACKGROUND Hepatocellular carcinoma(HCC),often diagnosed at advanced stages without curative therapies,is the fifth most common malignant cancer and the second leading cause of cancer-related mortality.Polo-like kinas...BACKGROUND Hepatocellular carcinoma(HCC),often diagnosed at advanced stages without curative therapies,is the fifth most common malignant cancer and the second leading cause of cancer-related mortality.Polo-like kinase 1(PLK1)is activated in the late G2 phase of the cell cycle and is required for entry to mitosis.Interestingly,PLK1 is overexpressed in many HCC patients and is highly associated with poor clinical outcome.Baculoviral inhibitor of apoptosis repeatcontaining 5(BIRC5)is also highly overexpressed in HCC and plays key roles in this malignancy.AIM To determine the expression patterns of PLK1 and BIRC5,as well as their correlation with p53 mutation status and patient clinical outcome.METHODS The expression patterns of PLK1 and BIRC5,and their correlation with p53 mutation status or patient clinical outcome were analyzed using a TCGA HCC dataset.Cell viability,cell apoptosis,and cell cycle arrest assays were conducted to investigate the efficacy of the PLK1 inhibitors volasertib and GSK461364 and the BIRC5 inhibitor YM155,alone or in combination.The in vivo efficacy of volasertib and YM155,alone or in combination,was assessed in p53-mutated Huh7-derived xenograft models in immune-deficient NSIG mice.RESULTS Our bioinformatics analysis using a TCGA HCC dataset revealed that PLK1 and BIRC5 were overexpressed in the same patient subset and their expression was highly correlated.The overexpression of both PLK1 and BIRC5 was more frequently detected in HCC with p53 mutations.High PLK1 or BIRC5 expression significantly correlated with poor clinical outcome.PLK1 inhibitors(volasertib and GSK461364)or a BIRC5 inhibitor(YM155)selectively targeted Huh7 cells with mutated p53,but not HepG2 cells with wild-type p53.The combination treatment of volasertib and YM155 synergistically inhibited the viability of Huh7 cells via apoptotic pathway.The efficacy of volasertib and YM155,alone or in combination,was validated in vivo in a Huh7-derived xenograft model.CONCLUSION PLK1 and BIRC5 are highly co-expressed in p53-mutated HCC and inhibition of both PLK1 and BIRC5 synergistically compromises the viability of p53-mutated HCC cells in vitro and in vivo.展开更多
BACKGROUND: This study aimed to investigate the epidemiological and clinical characteristics of patients with heat-related illness, and guide the prevention, diagnosis and treatment of heat-related illness.METHODS: Fr...BACKGROUND: This study aimed to investigate the epidemiological and clinical characteristics of patients with heat-related illness, and guide the prevention, diagnosis and treatment of heat-related illness.METHODS: From June 2013 to August 2013, seventy patients with heat-related illness were treated at Jinshan Hospital of Fudan University, and their epidemiological characteristics, laboratory results, treatment and prognosis were retrospectively analyzed.RESULTS: In the 70 patients, 18 patients suffered from heat stroke and 52 patients from nonheat stroke. When the environmnent temperature was above 35 °C, the body temperature of the patients began to increase markedly. The patients with heat stroke were significantly older than those with non-heat stroke(P<0.05). The body temperature, heart rate, blood glucose, blood lactate dehydrogenase and blood creatine kinase in the patients with heat stroke were higher than those in the patients with non-heat stroke(P<0.05). Blood lactate dehydrogenase and blood creatine kinase were positively correlated with body temperature(r=0.801).CONCLUSION: When the environmental temperature goes above 35 °C, heat-related illness should be prevented, especially in the elderly. The body temperature, heart rate, blood glucose, blood lactate dehydrogenase and blood creatine kinase in patients with heat stroke are higher than those in patients with non-heat stroke. Blood lactate dehydrogenase and blood creatine kinase are positively correlated with body temperature, but their relationship with heat-related illness awaits further study.展开更多
Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration.Therefore,investigating how axon regeneration and degeneration work together to repair perip...Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration.Therefore,investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous system.In this study,we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve injury.We identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments,respectively.Functional enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration,while the differentially expressed genes in distal modules promoted neurodegeneration.Next,we constructed hub gene networks for selected modules and identified a key hub gene,Kif22,which was up-regulated in both nerve segments.In vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling pathway.Collectively,our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments,and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and migration.All animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University,China(approval No.S20210322-008)on March 22,2021.展开更多
Mitogen-activated protein kinase (MPK) cascades consist of a set of kinase types (MPKKKs, MPKKs, MPKs) to establish conserved signal-transducing modules mediating plant growth, development as well as responses to ...Mitogen-activated protein kinase (MPK) cascades consist of a set of kinase types (MPKKKs, MPKKs, MPKs) to establish conserved signal-transducing modules mediating plant growth, development as well as responses to internal and external cues. In this study, the expression patterns of six MPKKK, two MPKK, and 11 MPK genes in wheat in responses to external treatments of phytohormones, including naphthylacetic acid (NAA), abscisic acid (ABA), 6-benzyladenine (6-BA), gibber- ellin (GA3), salisylic acid (SA), jasmonic acid (JA), and ethylene (ETH), were investigated. Expression analysis revealed that several of the MPK cascade genes are responses to the external phytohormone signaling. Of which, TaMPKKKA;3 is induced by 6-BA and NAA while TaMPK4 repressed by ETH, GA3, SA, and JA; TaMPKKKA, TaMPKKKA;3 and TaMPK1 are down-regulated by ETH and GA3whereas TaMPK9 and TaMPK12 repressed by ETH and JA in addition that TaMPK12 also repressed by GA3; TaMPK12;1 is down-regulated by ABA, GA3 and SA while TaMPK17 repressed by all exogenous phytonormones examined. TaMPK4, a MPK type gene previously characterized to mediate tolerance to phosphate (Pi) deprivation, was functionally evaluated for its role in mediation of responses of plants to exogenous GA3, ETH, SA, and JA. Results indicated that overexpression and antisense expression of TaMPK4 in tobacco dramatically modify the growth of seedlings upon treatments of GA3, SA and JA, in which the overexpressors behaved deteriorated growth feature whereas the seedlings with antisense expression of TaMPK4 exhibited improved seedling phenotype. The growth behaviors in lines overexpressing or antisensely expressing TaMPK4 are closely associated with the biomass and the corresponding hormone-associated parameters. These results demonstrated that TaMPK4 acts as a critical player in mediating the phyto- hormone signaling. Our findings have identified the phytohormone-responsive MPK cascade genes in wheat and provided a connection between the phytohormone-mediated responses and the MPK cascade pathways.展开更多
基金Supported by The Suzhou Science and Technology Development Plan Guiding Project,No.SZSYYXH-2023-YB5The Suzhou Science and Technology Development Plan Project,No.SKY2023002The Suzhou Key Laboratory of Children's Structural Deformities,No.SZS2022018.
文摘BACKGROUND We report a rare case of primary clinical presentation featuring elevated creatine kinase(CK)levels in a neonate,which is associated with the LAMA2 gene.In this case,a heterozygous mutation in exon5 of the LAMA2 gene,c.715C>G(resulting in a change of nucleotide number 715 in the coding region from cytosine to gua-nine),induced an amino acid alteration p.R239G(No.239)in the patient,repre-senting a missense mutation.This observation may be elucidated by the neonatal creatine monitoring mechanism,a phenomenon not previously reported.CASE SUMMARY We analysed the case of a neonate presenting solely with elevated CK levels who was eventually discharged after supportive treatment.The chief complaint was identification of increased CK levels for 15 d and higher CK values for 1 d.Ad-mission occurred at 18 d of age,and despite prolonged treatment with creatine and vitamin C,the elevated CK levels showed limited improvement.Whole exo-me sequencing revealed the presence of a c.715C>G mutation in LAMA2 in the newborn,correlating with a clinical phenotype.However,the available informa-tion offers insufficient evidence for clinical pathogenicity.CONCLUSION Mutations in LAMA2 are associated with the clinical phenotype of increased neonatal CK levels,for which no specific treatment exists.Whole genome sequen-cing facilitates early diagnosis.
基金Supported by the Guangxi Zhuang Autonomous Region Health Commission Scientific Research Project,No.Z-A20220530.
文摘BACKGROUND Phosphoglycerate kinase 1(PGK1)has been identified as a possible biomarker for breast cancer(BC)and may play a role in the development and advancement of triple-negative BC(TNBC).AIM To explore the PGK1 and BC research status and PGK1 expression and mecha-nism differences among TNBC,non-TNBC,and normal breast tissue.METHODS PGK1 and BC related literature was downloaded from Web of Science Core Co-llection Core Collection.Publication counts,key-word frequency,cooperation networks,and theme trends were analyzed.Normal breast,TNBC,and non-TNBC mRNA data were gathered,and differentially expressed genes obtained.Area under the summary receiver operating characteristic curves,sensitivity and specificity of PGK1 expression were determined.Kaplan Meier revealed PGK1’s prognostic implication.PGK1 co-expressed genes were explored,and Gene Onto-logy,Kyoto Encyclopedia of Genes and Genomes,and Disease Ontology applied.Protein-protein interaction networks were constructed.Hub genes identified.RESULTS PGK1 and BC related publications have surged since 2020,with China leading the way.The most frequent keyword was“Expression”.Collaborative networks were found among co-citations,countries,institutions,and authors.PGK1 expression and BC progression were research hotspots,and PGK1 expression and BC survival were research frontiers.In 16 TNBC vs non-cancerous breast and 15 TNBC vs non-TNBC datasets,PGK1 mRNA levels were higher in 1159 TNBC than 1205 non-cancerous breast cases[standardized mean differences(SMD):0.85,95%confidence interval(95%CI):0.54-1.16,I²=86%,P<0.001].PGK1 expression was higher in 1520 TNBC than 7072 non-TNBC cases(SMD:0.25,95%CI:0.03-0.47,I²=91%,P=0.02).Recurrence free survival was lower in PGK1-high-expression than PGK1-low-expression group(hazard ratio:1.282,P=0.023).PGK1 co-expressed genes were concentrated in ATP metabolic process,HIF-1 signaling,and glycolysis/gluconeogenesis pathways.CONCLUSION PGK1 expression is a research hotspot and frontier direction in the BC field.PGK1 may play a strong role in promoting cancer in TNBC by mediating metabolism and HIF-1 signaling pathways.
基金Supported by the Taiwan Biotech Co., Taiwan, China
文摘AIM: To investigate whether American ginseng (AG, Panax quinquefolium) supplementation was able to improve endurance exercise performance.METHODS: Thirteen physically active male college students were divided into two groups (AG or placebo)and received supplementation for 4 wk, before the exhaustive running exercise. Treadmill speed was increased to a pace equivalent to 80% VO2max of the subject. A 4-wk washout period followed before the subjects crossed over and received the alternate supplement for the next 4 wk.They then completed a second exhaustive running exercise. The physiological variables that were examined included time to exhaustion and oxygen pulse. Moreover,the plasma creatine kinase (CK) and lactate were measured prior to the exercise, at 15 and 30 min during exercise,immediately after exercise, and 20, 40, 60, and 120 min after exercise.RESULTS: The major finding of this investigation was that the production plasma CK during the exercise significantly decreased for group AG than for group P. Secondary physiological finding was that 80% VO2max running was not improved over a 4-wk AG supplementation regimen.CONCLUSION: Supplementation with AG for 4 wk prior to an exhaustive aerobic treadmill running reduced the leakage of CK during exercise, but did not enhance aerobic work capacity. The reduction of plasma CK may be due to the fact that AG is effective for the decrease of skeletal muscle cell membrane damage, induced by exercise during the high-intensity treadmill run.
基金supported by the National Natural Science Foundation of China,No.81301093(to XPC)。
文摘Creatine kinase is a muscle enzyme that has been reported at various levels in different studies involving patients with amyotrophic lateral sclerosis.In the present retrospective case-control study,we included 582 patients with amyotrophic lateral sclerosis and 582 age-and sexmatched healthy controls.All amyotrophic lateral sclerosis participants received treatment in the Department of Neurology,West China Hospital,China,between May 2008 and December 2018.Serum creatine kinase levels in patients with amyotrophic lateral sclerosis were significantly higher than those in healthy controls.Subgroup analysis revealed that serum creatine kinase levels in men were higher than those in women in both amyotrophic lateral sclerosis patients and healthy controls.Compared with patients with bulbar-onset amyotrophic lateral sclerosis,patients with limb-onset amyotrophic lateral sclerosis had higher creatine kinase levels.Spearman's correlation analysis revealed that serum creatine kinase levels were not correlated with body mass index,Amyotrophic lateral Sclerosis Functional Rating ScaleRevised score,or progression rate.After adjusting for prognostic covariates,higher log creatine kinase values were correlated with higher overall survival in the amyotrophic lateral sclerosis patients.We also investigated the longitudinal changes in serum creatine kinase levels in 81 amyotrophic lateral sclerosis patients;serum creatine kinase levels were decreased at the second blood test,which was sampled at least 6 months after the first blood test.Together,our results suggest that serum creatine kinase levels can be used as an independent factor for predicting the prognosis of amyotrophic lateral sclerosis patients.This study received ethical approval from the Ethics Committee of West China Hospital,China(approval No.2015(236))on December 23,2015.
基金supported by the Key Project of Chinese Ministry of Education(Grant No.209076)the Basic Science Initiative Program of Henan Province,China(Grant No.092300410099)+1 种基金the Fund of the Henan Science Initiative,China(Grant No.092102110092)the Innovation Scientists and Technicians Troop Construction Projects of Henan Province,China(GrantNo.104100510012)
文摘Mitogen activated-protein kinases (MAPKs) are important components in signal transduction pathways responding to various biotic and abiotic stresses. An MAPK gene, OsMPK14 (GenBank Accession No. GQ265780) from rice (Oryza sativa L.), was cloned by RT-PCR. The full-length cDNA of OsMPK14 consists of 1660 bp in size, containing an open reading frame of 1629 bp, which encodes a 542-amino-acid polypeptide and has a typical protein kinase domain and a phosphorylation activation motif TDY. Sequence alignment and analysis revealed that OsMPK14 was located on rice chromosome 5, and composed of nine exons and eight introns in the coding region. Semi-quantitative RT-PCR was performed to detect the expression patterns of OsMPK14 in rice shoots and roots under darkness, drought, high salinity, low temperature and abscisic acid treatments. The OsMPK14 mRNA was induced by abscisic acid, low temperature and high salinity, but weakly inhibited by drought. In addition, the expression of OsMPK14 was up-regulated in roots, but down-regulated in shoots by light. The results indicate that OsMPK14 could be implicated in diverse rice stimuli-responsive signaling cascades, and its expression might be regulated by multiple factors.
文摘Summary: The effects of oligosaccharide and creatine (Cr) supplementation on glucose, lactic acid and urea nitrogen levels in blood and activity of serum creatine kinase (CK) were explored. Twenty CUBA male athletes were divided into 4 groups: group A (supplementation of Cr alone), group B (supplementation of oligosaccharide), group C (supplementation of oligosaccharide and Cr) and group D (placebo control group). By using orthogonal L4 table (2a ), the experiment was performed. There were factors including oligosaccharide (carbohydrate, CHO), Cr and their correlation. Each factor had two levels: supplementation and no-supplementation. The results showed that the supplementation of CliO or Cr alone, combined supplementation of CHO and Cr could significantly reduce the glucose, urea nitrogen levels in blood and serum CK activity after competition in the athletes. Moreover, the effects of combined supplementation of CHO and Cr were more satisfactory. It was concluded that supplementation of CliO and Cr could promote the recovery of physical performance and athletic abilities after athletics in basketball athletes.
基金Shenzhen Science and Technology Bureau, No.200405204
文摘BACKGROUND: Calcium antagonists may act as neuroprotectants, diminishing the influx of calcium ions through voltage-sensitive calcium channels. When administered prophylactically, they display neuroprotective effects against hypoxic-ischemic brain damage in newborn rats. OBJECTIVE: To investigate the neuroprotective effects of flunarizine (FNZ), lamotrigine (LTG) and the combination of both drugs, on hypoxic-ischemic brain damage in fetal rats. DESIGN AND SETTING: This randomized, complete block design was performed at the Department of Pediatrics, Shenzhen Fourth People's Hospital, Guangdong Medical College. MATERIALS: Forty pregnant Wistar rats, at gestational day 20, were selected for the experiment and were randomly divided into FNZ, LTG, FNZ + LTG, and model groups, with 10 rats in each group. METHODS: Rats in the FNZ, LTG, and FNZ + LTG groups received intragastric injections of FNZ (0.5 mg/kg/d), LTG (10 mg/kg/d), and FNZ (0.5 mg/kg/d) + LTG (10 mg/kg/d), respectively. Drugs were administered once a day for 3 days prior to induction of hypoxia-ischemia. Rats in the model group were not administered any drugs. Three hours after the final administration, eight pregnant rats from each group underwent model establishment hypoxia-ischemia brain damage to the fetal rats. Cesareans were performed at 6, 12, 24, and 48 hours later; and 5 fetal rats were removed from each mother and kept warm. Two fetuses without model establishment were removed by planned cesarean at the same time and served as controls. A total of 0.3 mL serum was collected from fetal rats at 6, 12, 24, and 48 hours, respectively, following birth. MAIN OUTCOME MEASURES: Serum protein concentrations of neuron-specific enolase and S-100 were measured by ELISA. Serum concentrations of brain-specific creatine kinase were measured using an electrogenerated chemiluminescence method. RESULTS: Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly higher in the hypoxic-ischemic fetal rats, compared with the non-hypoxic-ischemic group. Serum concentrations of neuron-specific enolase, S-100, and brain-specific creatine kinase were significantly less in the FNZ, LTG, and FNZ + LTG groups following ischemia, compared with the model group (P 〈 0.01). However, these values were significantly greater in the FNZ and LTG groups, compared with the FNZ + LTG group, following ischemia (P 〈 0.01). CONCLUSION: Preventive antenatal use of oral FNZ and LTG has positive neuroprotective effects on intrauterine hypoxic-ischemic brain damage. The combined effect of these two drugs is superior.
文摘Objective To study the differential diagnosis on cerebral concussion and mild cerebral contusion value of the brain type creatine kinase isoenzyme(CK BB),and evaluate the seriousness of brain damage and prognosis of the patients with acute head injury.Methods Chromatographic separating and fluorometric quantifying technique was used to detect the CK BB activity in the cerebrospinal fluid(CSF) of 117 patients with acute head injury and 12 patients with increased intracranial pressure and 20 normal people.Results The CSF CK BB activity of the patients with acute head injury was remarkably higher than that of the normal people and the CSF CK BB activity increased with the seriousness of brain damage.There was a close relationship between CSF CK BB activity and prognosis,and higher activity of CSF CK BB indicated poor prognosis.Conclusion CSF CK BB activity could be used as a new index to diagnose brain damage and evaluate the seriousness of brain damage and prognosis.
文摘Objective To observe the relationship between serum creatine kinase isoenzyme MM sub-bands (CKMM3/MM1 ratio) and the gradation of coronary stenosis and provide a simple, reliable, and economical method for identifying high-risk unstable angina pectoris (UAP). Mehtods Blood samples were drawn at different time after onset of chest pain in 21 patients with UAP and only once in 20 each volunteers for control. CKMM3/MM1 ratio was detected by nonserial buffer agarose gel electrophoresis. CKMB and CK were observed by velocity method. An emergent coronary arteriography was performed as soon as patients were admitted into hospital. Results Patients with UAP were divided into two subgroups: patients with elevated serum enzyme [P( + )] and patients with normal serum enzyme [P( - ) ] according to CKMM3/MM1 ratio < 0. 5. Patients with UAP( + ) had higher serum CKMM3/MM1 ratios from 0.5 to 12hrs and serum CKMB from 2 to 12 hrs than those with UAP( - ) and control ( P < 0. 05) . Serum enzyme concentrations of patients with UAP whose coronary lumen had 90% or more than 90% stenosis were significantly higher than those whose coronary lumen had less than 90% stenosis ( P <0. 01) . Any CK-MM3/MM1 ratio was less than 1. 0 and CK within the normal range in patients with UAP( + ) group. Conclusions CKMM3/MM1 ratios in patients with UAP can reflect severity of myocardial ischemia. SerumCKMM3/MM1 ratio provides a simple, reliable, and economical method for identifying high-risk UAP.
文摘Objective:To assess the correlation of signs of myocardial damage to serum cardiac troponin I(cTnI)and creatine kinase MB isoenzyme(CK-MB)concentrations.Methods:Blood samples were collected from 25 term asphyxiated neonates and 25 controls at 12 h of age by immunoassay.The asphyxiated neonates were followed up until discharge or death.Results:Asphyxiated neonates had significantly higher concentrations of cTnI and CK-MB than controls(P<0.001).Serum cTnI concentrations were significantly higher in asphyxiated neonates who developed hypotension,heart failure or those had low ejection fraction(P<0.01).Serum cTnI concentrations were significantly higher in asphyxiated who died than those who survived(P<0.01).There was no significant difference in serum CK-MB mass concentrations between asphyxiated neonates with and without these complications.Conclusion:Unlike CK-MB,serum cTnI concentrations are significantly higher in asphyxiated neonates who died or developed cardiac dysfunction.
基金supported by National Key Research and Development Program of China(2022YFD1200202)State Key Laboratory of North China Crop Improvement and Regulation(NCCIR2022ZZ-7)Graduate Student Innovation Ability Training Funding Project of Hebei Province(CXZZBS2023073)。
文摘SNF1-related protein kinase 2(SnRK2)family members are essential components of the plant abscisic acid(ABA)signaling pathway initiated by osmotic stress and triggering a drought stress response.This study characterized the molecular properties of TaSnRK2.4 and its function in mediating adaptation to drought in Triticum aestivum.Transcripts of TaSnRK2.4 were upregulated upon drought and ABA signaling and associated with drought-and ABA-responsive cis-elements ABRE and DRE,and MYB and MYC binding sites in the promoter as indicated by reporter GUS protein staining and activity driven by truncations of the promoter.Yeast two-hybrid,BiFC,and Co-IP assays indicated that TaSnRK2.4 protein interacts with TaPP2C01 and an ABF transcription factor(TF)TaABF2.The results suggested that TaSnRK2.4 forms a functional TaPP2C01-TaSnRK2.4-TaABF2 module with its upstream and downstream partners.Transgene analysis revealed that TaSnRK2.4 and TaABF2 positively regulate drought tolerance whereas TaPP2C01 acts negatively by modulating stomatal movement,osmotic adjustment,reactive oxygen species(ROS)homeostasis,and root morphology.Expression analysis,yeast one-hybrid,and transcriptional activation assays indicated that several osmotic stress-responsive genes,including TaSLAC1-4,TaP5CS3,TaSOD5,TaCAT1,and TaPIN4,are regulated by TaABF2.Transgene analysis verified their functions in positively regulating stomatal movement(TaSLAC1-4),proline accumulation(TaP5CS3),SOD activity(TaSOD5),CAT activity(TaCAT1),and root morphology(TaPIN4).There were high correlations between plant biomass and yield with module transcripts in a wheat variety panel cultivated under drought conditions in the field.Our findings provide insights into understanding plant drought response underlying the SnRK2 signaling pathway in common wheat.
文摘AIM To detect the expression of Raf kinase inhibitory protein(RKIP) in gastrointestinal stromal tumors(GISTs) and to analyze its relationship with clinicopatholgical characteristics and prognosis of this disease.METHODS Sixty-three patients with pathologically diagnosed GISTs who underwent surgical resection at the Shengjing Hospital of China Medical University from January 2011 to January 2015 and had complete clinical,pathological,and follow-up data were included. Immunohistochemical method was used to detect the expression of RKIP in GIST tissue samples from these patients. KaplanMeier method was used to calculate the survival rate of 60 patients with complete follow-up data,and Cox regression analysis was performed to identify factors affecting the prognosis of patients GISTs to evaluate further the diagnostic and prognostic value of RKIP in GISTs.RESULTS In GIST tissues,RKIP positive signals,manifesting as brownish yellow or brown granules,were located in the cytoplasm or on the membrane. Of 63 tissue samplesincluded in this study,34(54%) were positive and 29(46%) were negative for RKIP expression. Statistical analysis showed that RKIP expression in GISTs was significantly associated with tumor size,National Institutes of Health(NIH) risk grade,and mucosal invasion,but had no significant association with age,gender,tumor location,or the number of mitotic figures. Univariate Kaplan-Meier analysis revealed that the 1-,3-,and 5-year survival rates were 94.4%,89.2%,and 80.5% for patients with positive RKIP expression,and 88.6%,68.2%,and 48.2% for patients with negative RKIP expression,suggesting that patients with high RKIP expression had significantly higher survival rates than those with low expression(Log-rank test,P = 0.0015). Cox regression analysis demonstrated that NIH risk grade was significantly associated with the prognosis of GISTs(P = 0.037),suggesting that NIH risk grade is a significant predictor of the prognosis of GISTs. RKIP expression had a tendency to predict the survival of GISTs(P = 0.122),suggesting that RKIP expression may have appreciated value to predict the prognosis of GISTs.CONCLUSION This study demonstrated that:(1) RKIP expression in GISTs is associated with tumor size,NIH risk grade,and mucosal invasion,and low or no expression of RKIP predicts a high malignancy potential;(2) high RKIP correlates positively with the survival of patients with GISTs; and(3) RKIP expression has appreciated value for predicting the survival of patients with GISTs,although it is not an independent prognostic factor in GISTs.
基金supported by the National Natural Science Foundation of China(31601307)the Key Scientific and Technological Innovation Platform of the Main Crop Germplasm Innovation and Molecular Breeding in Shanxi Province,China(201605D151002)the Youth Foundation of Institute of Crop Science,Shanxi Academy of Agricultural Sciences(ZZQ1701)
文摘Resistance gene analog(RGA) screening of mapped disease-resistant genes not only helps to clone these genes but also helps to develop efficient molecular markers for resistance breeding. The present study focused on the PmU region located on chromosome 7 Au L of Triticum urartu, and recently, a nucleotide binding site(NBS)-encoding gene, Pm60, was cloned from the same chromosome arm. In this research, NBS, protein kinase(PK), and ATP-binding cassette(ABC), the three disease resistance-related gene families, were analyzed within PmU region by using informatics tools, and an expression experiment was conducted to verify their functions in vivo. Comparative genomic analysis revealed that 126 RGAs were included on chromosome 7 Au L, and 30 of the RGAs as well as Pm60 were found in the Pm U region. Transcriptome database analysis of T. urartu revealed 14 PmU-RGAs with expression data, and three PmU-NBSs exhibited significant changes in expression after inoculation with Blumeria graminis f. sp. tritici(Bgt); TRIUR314879 was up-regulated, while TRIUR300450 and TRIUR306270 were down-regulated. Cluster analysis showed that these three PmU-NBSs were clustered far from the cloned wheat resistance genes. Then, qRT-PCR was performed to investigate the expression of 14 PmU-RGAs and Pm60 after inoculation with Bgt race E09; the results showed that Pm60 was specifically expressed in UR206 which carrying PmU, but not in susceptible UR203; while TRIUR314879 was significantly up-regulated and TRIUR300450 was downregulated in UR206 after inoculation. These results indicated that PmU is Pm60, and TRIUR314879 and TRIUR300450 may also be involved in the defense against Bgt.
文摘AIM: To elucidate the role of overexpressed polo-like kinasel (PLK1)in hepatocellular carcinoma (HCC). METHODS: We prospectively collected clinicopathological, immunohistochemical and semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) data from 135 HCC patients undergoing successful hepatectomy. The correlations between PLK1 mRNA expression and clinicopathologic variables were analyzed by Mann-Whitney U test. Prognostic factors were identified by univariate and multivariate analyses. RESULTS: Immunohistochemical results showed overexpression of PLK1 was mainly found in tumor tissues compared with tumor-free tissue. A similar mRNA result was obtained by semi-quantitative RT-PCR. A total of 111 samples were positive for PLK1 mRNA expression. The positive expression was correlated with venous invasion, tumor nodules and Edmondson grade. Furthermore, 1, 3, 5-year survival rates in the positive expression group were significantly lower than the negative control group. Multivariate analysis showed that positive PLK1 expression was an independent risk factor for HCC. CONCLUSION: PLK1 could be a potential biomarker for diagnosis and therapy for HCC.
基金funded by the National Natural Science Foundation of China(31271799)the National "Key Sci-Tech" program,China(2013ZX08002-001-004)the China–Czech Government Science and Technology Cooperation Project(40–3 and LH12196)
文摘Wall-associated kinases(WAKs) play an important role in plant defense and development.Considerable progress has been made in understanding WAK genes in Arabidopsis thaliana.However, much less is known about these genes in common wheat. Here, we isolated a novel wheat WAK gene TaWAK5 from sharp eyespot disease-resistant wheat line CI12633,based on a differentially-expressed sequence identified by microarray analysis. The transcript abundance of TaWAK5 was rapidly increased following inoculation with the pathogen Rhizoctonia cerealis. TaWAK5 in resistant wheat lines was induced to higher levels than in susceptible lines at 7 days post inoculation with R. cerealis. The expression of TaWAK5 was also induced by treatments with exogenous salicylic acid, abscisic acid, and methyl jasmonate. The deduced TaWAK5 protein contained a signal peptide, two epidermal growth factor(EGF)-like repeats, a transmembrane domain, and a serine/threonine protein kinase catalytic domain. Subcellular localization analyses in onion epidermal cells indicated that the TaWAK5 protein was localized to the plasma membrane. Virus-induced gene silencing of TaWAK5 in CI12633 plants showed that the silencing of TaWAK5 did not obviously impair wheat resistance to R. cerealis, suggesting that TaWAK5 may be not the major gene in wheat defense response to R. cerealis, or that it is functionally redundant with other genes. This study paves the way for further research into WAK functions in wheat stress physiology.
基金Supported by National Science and Technology Major Project,No.2018ZX10732-202-004Tianjin Science and Technology Plan Project,No.17JCYBJC26100 and No.19ZXDBSY00030.
文摘BACKGROUND Hepatocellular carcinoma(HCC),often diagnosed at advanced stages without curative therapies,is the fifth most common malignant cancer and the second leading cause of cancer-related mortality.Polo-like kinase 1(PLK1)is activated in the late G2 phase of the cell cycle and is required for entry to mitosis.Interestingly,PLK1 is overexpressed in many HCC patients and is highly associated with poor clinical outcome.Baculoviral inhibitor of apoptosis repeatcontaining 5(BIRC5)is also highly overexpressed in HCC and plays key roles in this malignancy.AIM To determine the expression patterns of PLK1 and BIRC5,as well as their correlation with p53 mutation status and patient clinical outcome.METHODS The expression patterns of PLK1 and BIRC5,and their correlation with p53 mutation status or patient clinical outcome were analyzed using a TCGA HCC dataset.Cell viability,cell apoptosis,and cell cycle arrest assays were conducted to investigate the efficacy of the PLK1 inhibitors volasertib and GSK461364 and the BIRC5 inhibitor YM155,alone or in combination.The in vivo efficacy of volasertib and YM155,alone or in combination,was assessed in p53-mutated Huh7-derived xenograft models in immune-deficient NSIG mice.RESULTS Our bioinformatics analysis using a TCGA HCC dataset revealed that PLK1 and BIRC5 were overexpressed in the same patient subset and their expression was highly correlated.The overexpression of both PLK1 and BIRC5 was more frequently detected in HCC with p53 mutations.High PLK1 or BIRC5 expression significantly correlated with poor clinical outcome.PLK1 inhibitors(volasertib and GSK461364)or a BIRC5 inhibitor(YM155)selectively targeted Huh7 cells with mutated p53,but not HepG2 cells with wild-type p53.The combination treatment of volasertib and YM155 synergistically inhibited the viability of Huh7 cells via apoptotic pathway.The efficacy of volasertib and YM155,alone or in combination,was validated in vivo in a Huh7-derived xenograft model.CONCLUSION PLK1 and BIRC5 are highly co-expressed in p53-mutated HCC and inhibition of both PLK1 and BIRC5 synergistically compromises the viability of p53-mutated HCC cells in vitro and in vivo.
文摘BACKGROUND: This study aimed to investigate the epidemiological and clinical characteristics of patients with heat-related illness, and guide the prevention, diagnosis and treatment of heat-related illness.METHODS: From June 2013 to August 2013, seventy patients with heat-related illness were treated at Jinshan Hospital of Fudan University, and their epidemiological characteristics, laboratory results, treatment and prognosis were retrospectively analyzed.RESULTS: In the 70 patients, 18 patients suffered from heat stroke and 52 patients from nonheat stroke. When the environmnent temperature was above 35 °C, the body temperature of the patients began to increase markedly. The patients with heat stroke were significantly older than those with non-heat stroke(P<0.05). The body temperature, heart rate, blood glucose, blood lactate dehydrogenase and blood creatine kinase in the patients with heat stroke were higher than those in the patients with non-heat stroke(P<0.05). Blood lactate dehydrogenase and blood creatine kinase were positively correlated with body temperature(r=0.801).CONCLUSION: When the environmental temperature goes above 35 °C, heat-related illness should be prevented, especially in the elderly. The body temperature, heart rate, blood glucose, blood lactate dehydrogenase and blood creatine kinase in patients with heat stroke are higher than those in patients with non-heat stroke. Blood lactate dehydrogenase and blood creatine kinase are positively correlated with body temperature, but their relationship with heat-related illness awaits further study.
基金supported by the National Major Project of Research and Development of China,No.2017YFA0104701(to BY)the National Natural Science Foundation of China,No.32000725(to QQC)+1 种基金the Natural Science Foundation of Jiangsu Province of China,No.BK20200973(to QQC)the Jiangsu Provincial University Innovation Training Key Project of China,No.202010304021Z(to ML)。
文摘Peripheral nerve injury repair requires a certain degree of cooperation between axon regeneration and Wallerian degeneration.Therefore,investigating how axon regeneration and degeneration work together to repair peripheral nerve injury may uncover the molecular mechanisms and signal cascades underlying peripheral nerve repair and provide potential strategies for improving the low axon regeneration capacity of the central nervous system.In this study,we applied weighted gene co-expression network analysis to identify differentially expressed genes in proximal and distal sciatic nerve segments from rats with sciatic nerve injury.We identified 31 and 15 co-expression modules from the proximal and distal sciatic nerve segments,respectively.Functional enrichment analysis revealed that the differentially expressed genes in proximal modules promoted regeneration,while the differentially expressed genes in distal modules promoted neurodegeneration.Next,we constructed hub gene networks for selected modules and identified a key hub gene,Kif22,which was up-regulated in both nerve segments.In vitro experiments confirmed that Kif22 knockdown inhibited proliferation and migration of Schwann cells by modulating the activity of the extracellular signal-regulated kinase signaling pathway.Collectively,our findings provide a comparative framework of gene modules that are co-expressed in injured proximal and distal sciatic nerve segments,and identify Kif22 as a potential therapeutic target for promoting peripheral nerve injury repair via Schwann cell proliferation and migration.All animal experiments were approved by the Institutional Animal Ethics Committee of Nantong University,China(approval No.S20210322-008)on March 22,2021.
基金financially supported by the National Natural Science Foundation of China (31371618,31201674)the National Transgenic Major Program of China (2011ZX08008)the Key Laboratory of Crop Growth Regulation of Hebei Province,China
文摘Mitogen-activated protein kinase (MPK) cascades consist of a set of kinase types (MPKKKs, MPKKs, MPKs) to establish conserved signal-transducing modules mediating plant growth, development as well as responses to internal and external cues. In this study, the expression patterns of six MPKKK, two MPKK, and 11 MPK genes in wheat in responses to external treatments of phytohormones, including naphthylacetic acid (NAA), abscisic acid (ABA), 6-benzyladenine (6-BA), gibber- ellin (GA3), salisylic acid (SA), jasmonic acid (JA), and ethylene (ETH), were investigated. Expression analysis revealed that several of the MPK cascade genes are responses to the external phytohormone signaling. Of which, TaMPKKKA;3 is induced by 6-BA and NAA while TaMPK4 repressed by ETH, GA3, SA, and JA; TaMPKKKA, TaMPKKKA;3 and TaMPK1 are down-regulated by ETH and GA3whereas TaMPK9 and TaMPK12 repressed by ETH and JA in addition that TaMPK12 also repressed by GA3; TaMPK12;1 is down-regulated by ABA, GA3 and SA while TaMPK17 repressed by all exogenous phytonormones examined. TaMPK4, a MPK type gene previously characterized to mediate tolerance to phosphate (Pi) deprivation, was functionally evaluated for its role in mediation of responses of plants to exogenous GA3, ETH, SA, and JA. Results indicated that overexpression and antisense expression of TaMPK4 in tobacco dramatically modify the growth of seedlings upon treatments of GA3, SA and JA, in which the overexpressors behaved deteriorated growth feature whereas the seedlings with antisense expression of TaMPK4 exhibited improved seedling phenotype. The growth behaviors in lines overexpressing or antisensely expressing TaMPK4 are closely associated with the biomass and the corresponding hormone-associated parameters. These results demonstrated that TaMPK4 acts as a critical player in mediating the phyto- hormone signaling. Our findings have identified the phytohormone-responsive MPK cascade genes in wheat and provided a connection between the phytohormone-mediated responses and the MPK cascade pathways.