Salivary C-reactive protein and mean platelet volume as possible diagnostic markers for late-onset neonatal pneumonia

BACKGROUND Neonatal sepsis,a formidable threat to newborns,is a leading cause of neonatal mortality,with late-onset sepsis manifesting after 72 hours post-birth being particularly concerning.Pneumonia,a prevalent sepsis presentation,poses a significant risk,especially during the neonatal phase when lung defenses are compromised.Accurate diagnosis of pneumonia is imperative for timely and effective interventions.Saliva,a minimally invasive diagnostic medium,holds great promise for evaluating infections,especially in infants.AIM To investigate the potential of serum C-reactive protein(CRP),salivary CRP(sCRP),and mean platelet volume(MPV)as diagnostic markers for late-onset neonatal pneumonia(LONP).METHODS Eighty full-term neonates were systematically examined,considering anthropometric measurements,clinical manifestations,radiology findings,and essential biomarkers,including serum CRP,sCRP,and MPV.RESULTS The study reveals noteworthy distinctions in serum CRP levels,MPV,and the serum CRP/MPV ratio between neonates with LONP and healthy controls.MPV exhibited a robust discriminatory ability[area under the curve(AUC)=0.87]with high sensitivity and specificity at a cutoff value of>8.8.Correlations between serum CRP,sCRP,and MPV were also identified.Notably,sCRP demonstrated excellent predictive value for serum CRP levels(AUC=0.89),underscoring its potential as a diagnostic tool.CONCLUSION This study underscores the diagnostic promise of salivary and serum biomarkers,specifically MPV and CRP,in identifying and predicting LONP among neonates.These findings advocate for further research to validate their clinical utility in larger neonatal cohorts.

MicroRNAs as diagnostic markers and therapeutic targets for traumatic brain injury

Traumatic brain injury （TBI） is characterized by primary damage to the brain from the external mechanical force and by subsequent secondary injury due to various molecular and pathophysiological responses that eventually lead to neuronal cell death. Secondary brain injury events may occur minutes, hours, or even days after the trauma, and provide valuable therapeutic targets to prevent further neuronal degeneration. At the present time, there is no effective treatment for TBI due, in part, to the widespread impact of numerous complex secondary biochemical and pathophysiological events occurring at different time points following the initial injury. MicroRNAs control a range of physiological and pathological functions such as develop- ment, differentiation, apoptosis and metabolism, and may serve as potential targets for progress assessment and intervention against TBI to mitigate secondary damage to the brain. This has implications regarding improving the diagnostic accuracy of brain impairment and long-term outcomes as well as potential novel treatments. Recent human studies have identified specific microRNAs in serum/plasma （miR-425-p, -21, -93, -191 and -499） and cerebro-spinal fluid （CSF） （miR-328, -362-3p, -451, -486a） as possible indicators of the diagnosis, severity, and prognosis of TBI. Experimental animal studies have examined specific microRNAs as biomarkers and therapeutic targets for moderate and mild TBI （e.g., miR-21, miR-23b）. MicroRNA profil- ing was altered by voluntary exercise. Differences in basal microRNA expression in the brain of adult and aged animals and alterations in response to TBI （e.g., miR-21） have also been reported. Further large-scale studies with TBI patients are needed to provide more information on the changes in microRNA profiles in different age groups （children, adults, and elderly）.

Cerebrospinal fluid diagnostic markers for two-dimensional electrophoresis-mass spectrometry in Parkinson’s disease patients

BACKGROUND： Previous studies have confirmed the existence of specific proteins in body fluid of Parkinson＇s disease （PD） patients. However, the existing research has contained several interference factors with poor reproducibility and has not focused on patients grouped according to disease duration. OBJECTIVE： To verify differential expression of proteins in cerebrospinal fluid of PD patients grouped in order of disease severity through the use of two-dimensional electrophoresis-mass spectrometry methods. DESIGN, TIME AND SETTING： The proteomic-based, case-control study was performed between September 2008 and June 2009 at the Key Laboratory of Neurology in the First Affiliated Hospital of Chongqing Medical University. PARTICIPANTS： A total of 52 outpatients and/or inpatients, who were admitted to the Department of Neurology in the First Affiliated Hospital of Chongqing Medical University between 2008 and 2009, were randomized into the present study. Among them, 27 PD patients served as the PD group and were assigned to three subgroups according to modified Webster, Hoehn, and Yahr rating scales： 14 = mild, 8 = moderate, and 5 = severe; non-PD group of 16 patients included 5 cases of viral meningitis, 3 cases of acute myelitis, 1 case of Guillain-Barre syndrome, 2 cases of tuberculous meningitis, 2 cases of restless legs syndrome, and 3 cases of essential tremor; control group （n = 9） consisted of muscular tension headache in 6 cases, as well as syncope, trigeminal neuralgia, idiopathic orthostatic hypotension in 1 case. METHODS： Cerebrospinal fluid was collected from the involved patients using the lumbar puncture method. Proteins in the cerebrospinal fluid were separated by two-dimensional electrophoresis. MAIN OUTCOME MEASURES： Characteristics of protein electrophoresis patterns were analyzed, differentially expressed proteins were detected using matrix-assisted laser desorption ionization time of flight mass spectrometry, and protein data were analyzed in the Mascot database. RESULTS： Five protein electropherograms were analyzed by PDQuest 8.0, and （789 ± 32） protein spots were observed. There were significant differences in four protein spots in each of the PD sub-groups compared with the non-disease and control groups. Expression was down-regulated in three protein spots and up-regulated in one protein spot; 100% repetition rate was observed in four protein spots. According to the Mascot database, protein spots with down-regulated expression were as follows： DNA-guided RNA polymerase III subunit RPC5 （score： 50 points）; double serine, threonine, and tyrosine protein kinase （score： 64 points, P 〈 0.05）; activity-regulated cytoskeleton-associated protein （score： 58 points, P 〈 0.05）. However, G2 mitotic-specific cyclin was up-regulated （score： 84 points, P 〈 0.05）. CONCLUSION： Differential protein expression in the cerebrospinal fluid of PD patients was detected by two-dimensional electrophoresis-mass spectrometry, revealing changes in DNA-guided RNA polymerase III subunit RPC5, double serine, threonine, and tyrosine protein kinase, activity-regulated cytoskeleton-associated protein, and G2 mitotic cell cyclin, with good reproducibility.

Thick tongue coating: diagnostic markers for metastatic colorectal cancer?

Background:According to World Health Organization,colorectal cancer is the third most common cancer in the world.The prognosis assessment and condition judgment of the colorectal cancer remains a challenge clinically.Therefore,identification of diagnostic markers to evaluate the prognosis of colorectal cancer clinically should be urgently developed.We have observed that a lot of cancer patients had thick tongue clinically,but what is the relationship between tongue coating and the tumor?Methods:Seventy-four patients with colorectal carcinoma were collected through the outpatients of Tianjin Medical University Cancer Institute and Hospital from May 2010 to September 2011,in which there were 49 patients confirmed with recurrence or metastasis.All photos of patients’tongue were taken with a SONY camera in the same room and under constant conditions such as brightness or distance.Regression equation predicting thickness of tongue coating was constructed using binary logistic regression analysis.The optimal cut off of probabilities to diagnosis thick tongue coating was determined by receiver operating curve analysis.χ2 test for paired data and kappa test were used to determine the diagnostic value for recurrence and/or metastasis in colorectal cancer patients.Kolmogorov-Smirnov test was used to determine the distribution of ALT,AST,ALP ALB,TP,GLO,TBIL,DBIL,GGT,LDH,GLU,UA,CA724,CA199,CA242 and CEA.Data with the skewed distribution were presented as median(quartile interval).The association between the thickness of tongue coating and clinical-pathological character was evaluated by chi square test and two-independent-sample test.The two-independent-samplesχ2 was used to determine whether there were significant differences in the thin coating and thick coating between patients with recurrence and/or metastasis and patients without recurrence and/or metastasis.Kaplan-Meier method was used to analyze survival time.Statistical analysis was performed by SPSS(version 16.0).Results:Through retrospective clinical study we found that overall survival of colorectal cancer patients with thick greasy tongue coating is less than the patients with less tongue coating.What’s more,the risk for recurrence or/and metastasis overall survival in thick coating group was higher than thin coating group.In addition,the histological staining of the tongue slices of rats showed that EGFR receptors in the tongue root were the most among whole tongue surface.Tongue thick coating may be due to tumor patients with high levels of serum EGF which results in significantly increasing tongue coating.This finding suggested that the tongue coating of cancer patients may reflect the level of serum EGF levels in patients which may be related to shorter survival time.In addition,another study showed that serum lactic dehydrogenase level in patients with thick tongue coating is higher than patients with thin tongue coating.Conclusions:These studies suggest that tongue coating is likely to reflect some of the growth factor and enzyme levels.By observing the tongue coating we could predict the prognosis of patients and the characteristics of tongue coating may be used as new diagnostic markers to patients with colorectal carcinoma.

Screening of Postpartum Depression Diagnostic Markers Based on Immune-Related Genes and Immune Infiltration

Background:Postpartum depression(PPD)is a mild to severe non-psychotic depressive episode,one of the main factors leading to pregnancy-related morbidity and mortality,and a mental disorder that has not been fully diagnosed and treated.Compared with women without polycystic ovary syndrome,women with polycystic ovary syndrome are more likely to have a variety of pregnancy complications,including PPD.However,there is currently limited research on whether polycystic ovary syndrome is related to anxiety and depression during pregnancy,and whether this increases the risk of postpartum depression in women.Study design:The GSE10558 data set gene expression profile matrix was used for PPD expression profiles from Gene Expression Synthesis(GEO).The differentially expressed genes were selected and analyzed.Perform gene ontology(GO)enrichment and gene set variation analysis(GSVA)for annotation,visualization,and integrated discovery.At the same time,CIBERSORT and ESTIMATE were used to analyze the immune infiltration situation of the GSE10558 expression profile matrix,including the immune infiltration pattern of ovarian samples,and construct the immune cell infiltration(ICI)score.Then we screened the differentially expressed genes(DEGs)clustered with three groups of immune subtypes,and constructed a protein-protein interaction(PPI)and mRNA-miRNA-TF molecular interaction network.And further predicted the drug target of the hub gene and the target of small molecule compounds,and constructed a network.Based on the intersection of the phenotypic gene set,the pivot gene was identified.Finally,evaluate the expression differences of Hub genes between the data set groups,and generate receiver operating characteristic(ROC)curves to verify the diagnostic value of differentially expressed genes(DEG).Finally,genes with high area under the curve(AUC)values are validated.Results:We analyzed 222 DEGs with statistically significant differences in the GSE10558 data set by bioinformatics methods,of which 18 DEGs have significant differences.GO analysis showed that most of the 18 significantly differentially expressed genes were rich in receptor ligand activity and cytokine receptor binding.It is worth noting that these genes are also enriched in functional areas related to immune inflammatory response and immune cell regulation.The GSVA package was used for GSVA analysis,and the results showed that it was significantly enriched in growth factor binding and other aspects.And according to the ssGSEA analysis to obtain immune clustering groupings,the DEGs found in the high,medium,and low immune score groups are mainly enriched in immune inflammatory response and immune cell regulation through GO analysis.CIBERSORT analysis found that there are significant differences in memory B cells of 22 types of immune cells in ovarian samples.By mining the phenotypic gene set,the DEGs that are significantly related to PPD are intersected respectively,and four overlapping genes APOA1,PLN,PRKCZ,and TRPV2 are obtained as the most important pivot genes.We also use box plots to show the expression differences between tissue samples.The results show that there are significant differences in expression of these genes between groups,which may serve as new potential targets for the diagnosis and treatment of PPD.Subsequently,the ROC curve analysis of the four APOA1,PLN,PRKCZ,and TRPV2 that are significantly related to PPD showed significant prediction accuracy,and all AUCs were above 0.9,indicating that these new biomarkers can be further developed in PPD Research.Conclusion:The molecular markers APOA1,PLN,PRKCZ and TRPV2,which are closely related to immune cell function,can efficiently identify PPD.A diagnostic prediction model composed of these four immune function-related genes can distinguish PPD patients with different immune status.This discovery contributes to a more comprehensive understanding of the molecular mechanisms driving the occurrence and development of PPD,which is critical for improving the diagnosis,prognosis and treatment of this disease.

Development of diagnostic markers for a wheat leaf rust resistance gene Lr42 using RNA-sequencing

Wheat leaf rust is a prevalent foliar disease in wheat worldwide. Growing resistant cultivars is an effective strategy to minimize the impact of leaf rust on yield and grain quality. Lr42 is a leaf rust resistance gene identified from Aegilops tauschii and is still effective against current predominant leaf rust races in the United States and many other countries. In this study, we developed diagnostic DNA markers for Lr42 using the sequence polymorphisms of a differentially expressed gene(TaRPM1) encoding a putative NBARC protein in the Lr42 candidate region identified by RNA-sequencing of two near-isogenic lines contrasting in Lr42 alleles. Markers were designed based on a deletion mutation and a single nucleotide polymorphism(SNP) in the gene. Haplotype analyses of the newly developed markers in the three diversity panels demonstrated that they are diagnostic for Lr42, and superior to previously used markers in selection accuracy. These markers have the advantages of low cost and easy assay, and they are suitable for marker-assisted selection in breeding programs with either high-or low-throughput marker screening facilities.

Early diagnostic strategies for colorectal cancer

At present,cancer is still an important factor threatening human health.Colorectal cancer(CRC)is one of the top three most common cancers worldwide and one of the deadliest malignancies in humans.The latest data showed that CRC incidence and mortality rank third and second,respectively,among global malignancies.Early and accurate diagnosis is crucial to reduce the morbidity,mortality and improve survival of patients with CRC,but the current early diagnostic methods have limitations.The effectiveness and compliance of diagnostic methods have a certain impact on whether people choose screening.In this editorial,we explore strategies for the early diagnosis of CRC,including stool-based,blood-based,direct visualization,and imaging examinations.

MMP14 is a diagnostic gene of intrahepatic cholangiocarcinoma associated with immune cell infiltration

BACKGROUND Intrahepatic cholangiocarcinoma(ICC)is a malignant tumor of the hepatobiliary system with concealed onset,strong invasiveness and poor prognosis.AIM To explore the disease characteristic genes that may be helpful in the diagnosis of ICC and affect immune cell infiltration.METHODS We downloaded two ICC-related human gene expression profiles from GEO database as the training group(GSE26566 and GSE32958 datasets)for difference analysis,and performed enrichment analysis on differential genes.The least absolute shrinkage and selection operator(LASSO),support vector machinerecursive feature elimination(SVM-RFE)and random forest(RF),three machine learning algorithms,were used to screen the characteristic genes.Double verification was carried out on GSE107943 and The Cancer Genome Atlas,two verification groups.Receiver operating characteristic curve and area under the curve(AUC)were used to evaluate the diagnostic efficacy of genes for ICC.CIBERSORT and ssGSEA algorithms were used to evaluate the effect of characteristic genes on immune infiltration pattern.Human Protein Atlas(HPA)was used to analyze the protein expression level of the target gene.RESULTS A total of 1091 differential genes were obtained in the training group.Enrichment analysis showed that the above genes were mainly enriched in small molecular catabolism,complement and coagulation cascade,bile secretion and other functions and pathways.Twentyfive characteristic genes were screened by LASSO regression,19 by SVM-RFE algorithm,and 30 by RF algorithm.Three algorithms were used in combination to determine the characteristic gene of ICC:MMP14.The verification group confirmed that the genes had a high diagnostic accuracy(AUC values of the training group and the verification group were 0.960,0.999,and 0.977,respectively).Comprehensive analysis of immune infiltration showed that MMP14 could affect the infiltration of monocytes,activated memory CD4 T cells,resting memory CD4 T cells,and other immune cells,and was closely related to the expression of CD200,cytotoxic T-lymphocyteassociated antigen 4,CD14,CD44,and other immune checkpoints.The results of immunohistochemistry in HPA database showed was indeed overexpressed in ICC.CONCLUSION MMP14 can be used as a disease characteristic gene of ICC,and may regulate the distribution of immune-infiltrating cells in the ICC tumor microenvironment,which provides a new method for the determination of ICC diagnostic markers and screening of therapeutic targets.

Identification of prognostic indicators,diagnostic markers, and possible therapeutic targets among LIM homeobox transcription factors in breast cancer

Background:Breast cancer(BRCA)is the most common malignant tumor among women worldwide.Despite advances in treatment,many patients still die from a lack of effective diagnostic and prognostic markers and powerful therapeutic targets.LIM homeobox genes(LHXs)play vital roles in regulating the development of various organisms.However,there are limited reports regarding their roles in the diagnosis,prognosis,and treatment of BRCA.Methods:UALCAN,Kaplan–Meier plotter,cBioPortal,GeneMANIA,STRING,DAVID 6.8,TRRUST v2,LinkedOmics,and TIMER were utilized to analyze differential expression,prognostic value,genetic alteration,neighbor gene network,transcription factor targets,kinase targets,and immune cell infiltration of LHXs in BRCA patients.Results:LHX gene expression patterns are clear in BRCA and its different subtypes.Further analyses indicated that this altered expression is possibly affected by genetic and/or epigenetic changes.The prognostic and diagnostic values of certain LHXs are unique to different BRCA subtypes.LHXs are mainly involved in the regulation of differentiation and development,and their neighbor genes are primarily involved in cancer‐related pathways.Moreover,most LHXs are closely correlated with immune cell infiltration.Furthermore,LHXs may exert their functions by regulating a series of transcription factor and kinase targets.Conclusions:LHXs are unique diagnostic and prognostic markers and participate in cancer through different signaling pathways and/or regulatory mechanisms in BRCA.This study provides potential applications of LHXs for the diagnosis,prognosis,and treatment of BRCA and its different subtypes.

Diagnostic role of serum interleukin-18 in gastric cancer patients

AIM： To determine the current status in various aspects of gastric cancer patients and to find out the clinical correlation with prognostic role of serum interleukins in Thai patients. METHODS： Sixty-eight patients were enrolled in this study at King Chulalongkorn Memorial Hospital during April 2003 to May 2005. Gastric cancer was histologically proven in 51 patients and gastric ulcer in 17 patients. Serum IL-6, IL-10, IL-12, and IL-18 levels were measured by enzyme-linked immunosorbent assay （ELISA）. RESULTS： There were 26 males （55.32%） and 21 females （44.68%） with their age ranging from 33 to 85 years （mean age 64.49 ± 13.83 years）. The common presentations were weight loss （41.2%）, dyspepsia （39.2%）, and upper gastrointestinal bleeding （15.7%）. A total of 35.3% gastric cancer patients and 6.3% of gastric ulcer patients were smokers （P = 0.029）. Moreover, 32.4% of gastric cancer patients and 6.3% of gastric ulcer patients were alcoholic drinkers （P = 0.044）. Lesion location was pyloric-antrum in 39.4%, gastric body in 39.4%, upper stomach in 12.2% and entire stomach in 6.1% of the patients. H pylori infection was detected in 44.4%. The poorly-differentiated adenocarcinoma was the most common pathologic finding （60.7%）. Surgical treatment was performed in 44.1% patients （total gastrectomy in 5.9%, subtotal gastrectomy in 32.4% and palliative bypass surgery in 5.9%）. Systemic chemotherapy was given as an adjuvant therapy in 8.8% patients. Carcinomatosis peritoneii were found in 18.8% patients. The mean survival time was 13.03 ± 9.75 mo. The IL-18 level in gastric cancer patient group （58.54 ± 43.96 pg/mL） was significantly higher than that in gastric ulcer patient group （30.84± 11.18 pg/mL） （P = 0.0001） （95% CI was 42.20, 13.19）. The cut point of IL-18 for diagnosis of gastric cancer was 40 pg/mL, the positive predictive value was 92.31%. The IL-6 level in gastric cancer patients with distant metastasis （20.21 ±9.37 pg/mL） was significantly higher than that in those with no metastasis （10.13 ± 7.83 pg/mL） （P = 0.037） （95% CI was 19.51, 0.65）. The role of IL-10 and IL-12 levels in gastric cancer patients was to provide data with no significant difference.CONCLUSION： These findings demonstrate that serum IL-6 and IL-18, but not IL-10 and IL-12 levels may be the useful biological markers of clinical correlation and prognostic factor in patients with gastric cancer. Moreover, IL-18 could serve as a diagnostic marker for gastric cancer with a high positive predictive value.

Dysbiosis of the duodenal microbiota as a diagnostic marker for pancreaticobiliary cancer

BACKGROUND Pancreaticobiliary cancer(PB Ca)is a lethal disease,and a useful diagnostic marker is urgently needed.A correlation between the human microbiota and malignant gastrointestinal diseases was recently reported.AIM To investigate the efficacy of the duodenal microbiota for diagnosing PB Ca.METHODS We recruited 22 patients with benign pancreaticobiliary diseases(benign group)and 12 patients with PB Ca(malignant group).The duodenal microbiota of each patient was analyzed by the 16S rDNA terminal restriction fragment length polymorphism method.Patient characteristics,tumor markers,and relative abundances of the duodenal microbiota were compared between the benign and malignant groups.RESULTS Cancer antigen 19-9(CA19-9),Bifidobacterium,Clostridium cluster XVIII,and Prevotella levels differed significantly between the benign and malignant groups.Clostridium cluster XVIII had the greatest area under the receiver operating characteristic curve(AUC)among the four factors with respect to diagnosing PB Ca(cutoff value:3.038%;sensitivity:58.3%;specificity:95.2%;AUC:0.81).The combination of Clostridium cluster XVIII(cutoff value:3.038%)and CA19-9 Levels(cutoff value:18.8 U/mL)showed 91.7%sensitivity and 71.4%specificity for diagnosing PB Ca.CONCLUSION The duodenal microbiota may be useful for PB Ca screening.

Clinical diagnosis and management of pancreatic cancer: Markers, molecular mechanisms, and treatment options

Pancreatic cancer(PC)is the third-leading cause of cancer deaths.The overall 5-year survival rate of PC is 9%,and this rate for metastatic PC is below 3%.However,the PC-induced death cases will increase about 2-fold by 2060.Many factors such as genetic and environmental factors and metabolic diseases can drive PC development and progression.The most common type of PC in the clinic is pancreatic ductal adenocarcinoma,comprising approximately 90%of PC cases.Multiple pathogenic processes including but not limited to inflammation,fibrosis,angiogenesis,epithelial-mesenchymal transition,and proliferation of cancer stem cells are involved in the initiation and progression of PC.Early diagnosis is essential for curable therapy,for which a combined panel of serum markers is very helpful.Although some mono or combined therapies have been approved by the United States Food and Drug Administration for PC treatment,current therapies have not shown promising outcomes.Fortunately,the development of novel immunotherapies,such as oncolytic viruses-mediated treatments and chimeric antigen receptor-T cells,combined with therapies such as neoadjuvant therapy plus surgery,and advanced delivery systems of immunotherapy will improve therapeutic outcomes and combat drug resistance in PC patients.Herein,the pathogenesis,molecular signaling pathways,diagnostic markers,prognosis,and potential treatments in completed,ongoing,and recruiting clinical trials for PC were reviewed.

Laboratory evaluation in rheumatic diseases

Autoantibodies can help clinicians to allow early detection of autoimmune diseases and their clinical manifestations, to determine effective monitoring of prognosis and the treatment response. From this point, they have a high impact in rheumatic disease management. When usedcarefully they allow rapid diagnosis and appropriate treatment. However, as they may be present in healthy population they may cause confusion for interpreting the situation. False positive test results may lead to wrong treatment and unnecessary anxiety for patients. Autoantibody positivity alone does not make a diagnosis. Similarly, the absence of autoantibodies alone does not exclude diagnosis. The success of the test is closely related to sensitivity, specificity and likelihood ratios. So, interpretation of these is very important for a proper laboratory evaluation. In conclusion, in spite of the remarkable advances in science and technology, a deeply investigated anamnesis and comprehensive physical examination still continue to be the best diagnostic method. The most correct approach is that clinicians apply laboratory tests to confirm or exclude preliminary diagnosis based on anamnesis and physical examination. This review will discuss these issues.

Research progress on O-GlcNAcylation in the occurrence,development,and treatment of colorectal cancer

For a long time,colorectal cancer(CRC)has been ranked among the top cancerrelated mortality rates,threatening human health.As a significant posttranslational modification,O-GlcNAcylation plays an essential role in complex life activities.Related studies have found that the occurrence,development,and metastasis of CRC are all related to abnormal O-GlcNAcylation and participate in many critical biological processes,such as gene transcription,signal transduction,cell growth,and differentiation.Recently,nucleotide sugar analogs,tumorspecific carbohydrate vaccine,SIRT1 longevity gene,dendritic cells as targets,and NOTCH gene have become effective methods to induce antitumor therapy.Not long ago,checkpoint kinase 1 and checkpoint kinase 2 were used as therapeutic targets for CRC,but there are still many problems to be solved.With an in-depth study of protein chip,mass spectrometry,chromatography,and other technologies,O-GlcNAcylation research will accelerate rapidly,which may provide new ideas for the research and development of antitumor drugs and the discovery of new CRC diagnostic markers.

Urgent call for reconsideration of chronic kidney disease

Circulating toxins namely： free radicals, cytokines and metabolic products induce glomerular endothelial dys-function, hemodynamic maladjustment and chronic ischemic state;this leads to tubulointerstitial fbrosis in chronic kidney disease （CKD）. Altered vascular homeo-stasis observed in late stage CKD revealed defective angiogenesis and impaired nitric oxide production ex-plaining therapeutic resistance to vasodilator treatment in late stage CKD. Under current practice, CKD patients are diagnosed and treated at a rather late stage due to the lack of sensitivity of the diagnostic markers avail-able. This suggests the need for an alternative thera-peutic strategy implementing the therapeutic approachat an early stage. This view is supported by the normal or mildly impaired vascular homeostasis observed in early stage CKD. Treatment at this early stage can potentially enhance renal perfusion, correct the renal ischemic state and restore renal function. Thus, this alternative therapeutic approach would effectively pre-vent end-stage renal disease.

Fine-mapping and characterisation of genes on barley(Hordeum vulgare)chromosome 2H for salinity stress tolerance during germination

Salinity causes a detrimental impact on plant growth,particularly when the stress occurs during germination and early development stages.Barley is one of the most salt-tolerant crops;previously we mapped two quantitative trait loci(QTL)for salinity tolerance during germination on the short arm of chromosome 2 H using a CM72/Gairdner doubled haploid(DH)population.Here,we narrowed down the major QTL to a region of 0.341 or 0.439 Mb containing 9 or 24 candidate genes belonging to 6 or 20 functional gene families according to barley reference genomes v1 and v3 respectively,using two DH populations of CM72/Gairdner and Skiff/CM72,F_(2)and F;generations of CM72/Gairdner/;Spartacus CL,Two Receptorlike kinase 4(RLPK4)v1 or Receptor-like kinase(RLK)v3 could be the candidates for enhanced germination under salinity stress because of their upregulated expression in salt-tolerant variety CM72.Besides,several insertion/deletion polymorphisms were identified within the 3 rd exon of the genes between CM72 and Gairdner.The sequence variations resulted in shifted functional protein domains,which may be associated with differences in salinity tolerance.Two molecular markers were designed for selecting the locus with receptor-like protein kinase 4,and one was inside HORVU2 Hr1 G111760.1 or HORVU.MOREX.r3.2 HG0202810.1.The diagnostic markers will allow for pyramiding of 2 H locus in barley varieties and facilitate genetic improvement for saline soils.Further,validation of the genes to elucidate the mechanisms involved in enhancing salinity tolerance at germination and designing RLPK4 specific markers is proposed.For this publication,all the analysis was based on barley reference genome of2017(v1),and it was used throughout for consistence.However,the positions of the markers and genes identified were updated according to new genome(v3)for reference.

Clinical and prognostic significance of expression of phosphoglycerate mutase family member 5 and Parkin in advanced colorectal cancer

BACKGROUND Drugs targeting mitochondria can induce mitophagy and restrain proliferation in colorectal cancer(CRC)cells.Phosphoglycerate mutase family member 5(PGAM5)activates serine/threonine PTEN-induced putative kinase 1/Parkin pathway-mediated mitophagy.However,there are few studies on the clinical and prognostic significance of expression of PGAM5 protein and mitophagy-related protein Parkin in patients.AIM To assess the clinical significance of PGAM5 and Parkin proteins,as biomarkers for diagnosis and prognosis of CRC,by studying their expression in advanced CRC tissues and their association with clinicopathological parameters.METHODS The expression of PGAM5 and Parkin in CRC tissues from 100 patients was determined by immunohistochemistry.Each case was evaluated by using a combined scoring method based on signal intensity staining(scored 0-3)and the proportion of positively stained cancer cells(scored 0-4).The final staining score was calculated as the intensity score multiplied by the proportion score.Specimens were categorized as either high or low expression according to the Youden index,and the association between the expression of PGAM5 or Parkin and clinicopathological factors was ascertained.Additionally,we employed western blot to measure PGAM5 and Parkin protein expression in six matched pairs of CRC and adjacent non-tumor tissues.RESULTS Immunohistochemical and western blot findings showed that both PGAM5 and Parkin protein expression in tumor tissues was significantly higher than that in the adjacent tissues:PGAM5 and Parkin were mainly expressed in the cytoplasm of colonic epithelial cells.PGAM5 and Parkin protein levels were significantly positively correlated in advanced CRC tissues.Moreover,reduced Parkin protein expression was an independent prognostic factor for overall survival and progression-free survival in CRC patients as evinced by multivariate analysis.CONCLUSION The expression of PGAM5 protein and mitophagy-related protein Parkin has diagnostic significance for CRC and may become new biomarkers.Parkin may be a potential marker for the survival of CRC patients.

Role of the circulatory interleukin-6 in the pathogenesis of gliomas:A systematic review

BACKGROUND Glioma is the most common primary tumor in the brain originating from glial cells.In spite of extensive research,the overall survival rate is not enhanced.A number of published articles observed differentially circulating levels of cytokines in glioma.Interleukin-6(IL-6)protein coded by IL-6 gene is regulated by the immune system and it has been found to have a significant role in progression and apoptosis resistance of glioma.AIM To review the role of circulatory IL-6 in the development and progression of glioma and its utility as a biomarker.METHODS Preferred Reporting Items for Systematic Reviews and Meta-analysis(PRISMA)guidelines were applied to filter the relevant studies based on inclusion and exclusion criteria.We used a combination of keywords and the Reference Citation Analysis(RCA)tool to search the potential studies and performed data extraction from selected studies.RESULTS The published results were inconsistent;however,most studies showed a significantly higher IL-6 level in glioma cases as compared to controls.Comparative IL-6 level among the different grades of glioma showed a higher level with low-grade gliomas and lower level with high-grade gliomas.CONCLUSION IL-6 level significantly differed between cases and controls,and among different cancer stages,which shows its potential as a diagnostic and prognostic marker.

Clinical applications of exosome membrane proteins

Extracellular vesicles(EVs)are small membranous particles that can mediate cell-to-cell communication and which are divided into at least three categories according to their subcellular origin and size:exosomes,microvesicles,and apoptotic bodies.Exosomes are the smallest(30–150 nm)of these EVs,and play an important role in EV-mediated cell-to-cell interactions,by transferring proteins,nucleic acids and,lipids from their parental cells to adjacent or distant cells to alter their phenotypes.Most exosome studies in the past two decades have focused on their nucleic acid composition and their transfer ofmRNAs and microRNAs to neighboring cells.However,exosomes also carry specific membrane proteins that can identify the physiological and pathological states of their parental cells or indicate their preferential target cells or tissues.Exosome membrane protein expression can also be directly employed or modified to allow exosomes to serve as drug delivery systems and therapeutic platforms,including in targeted therapy approaches.This review will briefly summarize information on exosome membrane proteins components and their role in exosome–cell interactions,including proteins associated with specific cell-interactions and diseases,and the potential for using exosome membrane proteins in therapeutic targeting approaches.

Golgi protein 73, hepatocellular carcinoma and other types of cancers

Hepatocellular carcinoma(HCC)is one of the most common malignant tumors with a low survival rate.The identification of mechanisms underlying the development of HCC helps uncover cellular and mo-lecular targets for the diagnosis,prevention,and treatment of HCC.Golgi protein 73(GP73)level is up-regulated in HCC patients and potentially can be a therapeutic target.Despite many studies devoted to GP73 as a marker for HCC early diagnosis,there is little discussion about the function of GP73 in HCC tumorigenesis.Given the poor response to currently available HCC therapies,a better understanding of the role of GP73 in HCC may provide a new therapeutic target for HCC.The current paper summarizes the role of GP73 as a diagnostic marker as well as its roles in liver carcinogenesis.Its roles in other types of cancer are also discussed.