Inflammatory response in gastrointestinal cancers:Overview of six transmembrane epithelial antigens of the prostate in pathophysiology and clinical implications

Chronic inflammation is known to increase the risk of gastrointestinal cancers(GICs),the common solid tumors worldwide.Precancerous lesions,such as chronic atrophic inflammation and ulcers,are related to inflammatory responses in vivo and likely to occur in hyperplasia and tumorigenesis.Unfortunately,due to the lack of effective therapeutic targets,the prognosis of patients with GICs is still unsatisfactory.Interestingly,it is found that six transmembrane epithelial antigens of the prostate(STEAPs),a group of metal reductases,are significantly associated with the progression of malignancies,playing a crucial role in systemic metabolic homeostasis and inflammatory responses.The structure and functions of STEAPs suggest that they are closely related to intracellular oxidative stress,responding to inflammatory reactions.Under the imbalance status of abnormal oxidative stress,STEAP members are involved in cell transformation and the development of GICs by inhibiting or activating inflammatory process.This review focuses on STEAPs in GICs along with exploring their potential molecular regulatory mechanisms,with an aim to provide a theoretical basis for diagnosis and treatment strategies for patients suffering from these types of cancers.

Prevalence and Factors Associated with Positivity of Antinuclear Antibodies (ANA) Patterns, Native Anti-DNA and Extractable Nuclear Antigens (ENA) Antibodies: Experience from a Laboratory in Dakar

Background: Diagnosis of autoimmune diseases (AID) is challenging, due to overlapping features with other non-immune disorders. Anti-nuclear antibodies (ANA) are sensitive screening tests but anti-deoxyribonucleic acid-antibody (anti-DNA), and anti-extractable nuclear antigens (anti-ENA) are specific for AIDs. We aimed to look at ANA patterns in our patients and correlated them with anti-ENA for proper interpretation and better patient management cost-effectively. Methods: A retrospective study was conducted over 1 year from January to December 2022 who were tested for ANA at biology medical laboratory of Pasteur Institute of Dakar. Anti-ENA and anti-DNA results were also analyzed for ANA-positive patients. Statistical analysis was performed using STATA 14.0, p Results: 216 patients were analyzed. Women predominated at 79.2% and mean age was 48 years [CI 95%, 46 - 50], with extremes of 10 and 89. Most represented age group was [41 - 60] with 38%. ANA was positive in 27 (12.5%) of patients, 59.2% of whom were strongly positive (titer of 1/1000, 1/3200 or 1/6400). The most common pattern was nuclear speckled, which was found in 77.8% of samples. Anti-ENA and anti-DNA positivity in ANA-positive patients was found respectively in 63% (17/27) and 1.4% (3/27) of the samples analyzed. Most commonly identified anti-ENA was anti-Sm 29.6%, anti-SSA 29.6%, anti-Ro-52 25.9%, anti-RNP 18.5% and anti-SSB 14.8% which was associated with speckled pattern. Association results indicated a significant relationship between both tests and between ANA titer in the anti-ENA- and ANA-positive patients (p 0.001). Conclusions: ANA, Anti-ENA and anti-DNA antibodies are essential for AIDS diagnosis. However, the testing repertoire should follow an algorithm comprising of clinical features, followed by ANA results with nuclear, mitotic, and cytoplasmic patterns, anti-ENA, and anti-DNA for a more meaningful, and cost-effective diagnostic approach.

Six transmembrane epithelial antigens of the prostate to illustrate inflammatory response in gastrointestinal cancers

Gastrointestinal cancer(GIC)is a common and widespread form of tumor,with colonoscopy and upper gastrointestinal endoscopy available to detect relevant precancerous polyps and lesions.However,many patients are already in the late stages when first diagnosed with such cancer,resulting in a poor prognosis.Thus,it is necessary to explore new methods and research directions in order to improve the treatment of GIC.Given the specific nature of the gastrointestinal tract,research should focus on the mechanisms of various inflammations and the interactions between food entering and exiting from the gastrointestinal tract and cancer cells.Interestingly,six transmembrane epithelial antigens of the prostates(STEAPs)have been found to be significantly linked to the progression of malignant tumors,associated with intracellular oxidative stress and playing a major role in inflammation with their structure and function.This paper explores the mechanism of STEAPs in the inflammatory response of GIC,providing a theoretical basis for the prevention and early intervention of GIC.The basic properties of the STEAP family as metal reductase are also explained.When it comes to intervention for GIC prevention,STEAPs can affect the activity of Fe^(3+),Cu^(2+) reductase and regulate metal ion uptake in vivo,participating in inflammation-related iron and copper homeostasis.Thus,the mechanism of STEAPs on inflammation is of important value in the prevention of GIC.

Tumor neoantigens: Novel strategies for application of cancer immunotherapy

Neoantigen-targeted immunotherapy is a rapidly advancing field that holds great promise for treating cancer.The recognition of antigens by immune cells is a crucial step in tumor-specific killing,and neoantigens generated by mutations in cancer cells possess high immunogenicity and are selectively expressed in tumor cells,making them an attractive therapeutic target.Currently,neoantigens find utility in various domains,primarily in the realm of neoantigen vaccines such as DC vaccines,nucleic acid vaccines,and synthetic long peptide vaccines.Additionally,they hold promise in adoptive cell therapy,encompassing tumor-infiltrating cells,T cell receptors,and chimeric antigen receptors which are expressed by genetically modified T cells.In this review,we summarized recent progress in the clinical use of tumor vaccines and adoptive cell therapy targeting neoantigens,discussed the potential of neoantigen burden as an immune checkpoint in clinical settings.With the aid of state-of-the-art sequencing and bioinformatics technologies,together with significant advancements in artificial intelligence,we anticipated that neoantigens will be fully exploited for personalized tumor immunotherapy,from screening to clinical application.

Identification of tumor antigens and immune subtypes of hepatocellular carcinoma for mRNA vaccine development

BACKGROUND mRNA vaccines have been investigated in multiple tumors,but limited studies have been conducted on their use for hepatocellular carcinoma(HCC).AIM To identify candidate mRNA vaccine antigens for HCC and suitable subpopu-lations for mRNA vaccination.METHODS Gene expression profiles and clinical information of HCC datasets were obtained from International Cancer Genome Consortium and The Cancer Genome Atlas.Genes with somatic mutations and copy number variations were identified by cBioPortal analysis.The differentially expressed genes with significant prognostic value were identified by Gene Expression Profiling Interactive Analysis 2 website analysis.The Tumor Immune Estimation Resource database was used to assess the correlation between candidate antigens and the abundance of antigen-presenting cells(APCs).Tumor-associated antigens were overexpressed in tumors and associated with prognosis,genomic alterations,and APC infiltration.A consensus cluster analysis was performed with the Consensus Cluster Plus package to identify the immune subtypes.The weighted gene coexpression network analysis(WGCNA)was used to determine the candidate biomarker molecules for appropriate populations for mRNA vaccines.immune subtypes showed distinct cellular and clinical characteristics.The IS1 and IS3 immune subtypes were immunologically“cold”.The IS2 and IS4 immune subtypes were immunologically“hot”,and the immune checkpoint genes and immunogenic cell death genes were upregulated in these subtypes.IS1-related modules were identified with the WGCNA algorithm.Ultimately,five hub genes(RBP4,KNG1,METTL7A,F12,and ABAT)were identified,and they might be potential biomarkers for mRNA vaccines.CONCLUSION AURKA,CCNB1,CDC25C,CDK1,TRIP13,PES1,MCM3,PPM1G,NEK2,KIF2C,PTTG1,KPNA2,and PRC1 have been identified as candidate HCC antigens for mRNA vaccine development.The IS1 and IS3 immune subtypes are suitable populations for mRNA vaccination.RBP4,KNG1,METTL7A,F12,and ABAT are potential biomarkers for mRNA vaccines.

Expression and Evaluation of Wb-SXP-1 and Wb-123 Recombinant Antigens as Potential Diagnostic Biomarkers for Lymphatic Filariasis

Lymphatic filariasis (LF) remains a public health concern as it can cause permanent morbidity and disability to those infected. While the global elimination of LF in these endemic areas is ongoing through mass drug administration, there is the need to develop diagnostic tools that would be utilized to track the progress of total global eradication as well as perform surveillance for the recurrence of lymphatic filariasis transmission. Currently, approved LF diagnosis tools are faced with lack of specificity, low sensitivity, and periodicity dependence. Recombinant filarial antigen-based assays can address these drawbacks and offer practical instruments for LF diagnosis and surveillance. This present study, evaluated rWb-SXP-1 and rWb-123 antigens as potential diagnostic biomarker tools for Wuchereria banchrofti in human sera using microspheres-based multiplex serological assay. Based on statistical analysis using XLSTAT 2019 (Addinsoft) on data generated from multiplex technology assay, generated ROC curves for both rWb-SXP-1 and rWb-123 demonstrated 87.1% sensitivity to Wuchereria banchrofti human sera with rWb-SXP-1 antigens having the highest specificity of 96%. Indication that rWb-SXP-1 and rWb-123 antigens are capable of detecting immunoglobulin G4 (IgG4) antibodies in human sera synthesized specifically against W. banchrofti infections. Therefore, rWb-SXP-1 and rWb-123 antigens can be utilized to detect W. banchrofti infections by antibody profiling with excellent diagnostic sensitivity and specificity using microsphere-based multiplex serological tests. This method can be particularly practical for screening a large number of sera samples and/or for quick, extensive field-testing due to the high-throughput and quick formats applied.

False positive detection of serum cryptococcal antigens due to insufficient sample dilution:A case series

At present,with the development of technology,the detection of cryptococcal antigen(CRAG)plays an increasingly important role in the diagnosis of cryptococcosis.However,the three major CRAG detection technologies,latex agglutination test(LA),lateral flow assay(LFA)and Enzyme-linked Immunosorbent Assay,have certain limitations.Although these techniques do not often lead to false-positive results,once this result occurs in a particular group of patients(such as human immunodeficiency virus patients),it might lead to severe consequences.

Tumor-Specific Histo-Blood Group Antigens: Apropos of Two Cases

Cancer cells with immunogenic properties having altered protein glycosylation, modified blood group substances have been widely studied. Due to the genetic instability occurring during carcinogenesis the glycosyltransferases may suffer from posttranslation sequence modification. The author describes 2 autopsy cases, where in the background of the unusual metastatic tumor presentation, incompatible blood group antigenic determinants have been demonstrated using blood group specific lectins and monoclonal antibodies (mAb). In the first case, reported here, a 10-year-old girl developed an acute myeloid leukemia and died in a septic endotoxin shock after successful cytostatic treatment of a juvenile signet ring cell cancer of her colon. At autopsy there were no signs of tumor except bilateral apple-sized mucinous ovarian (Krukenberg) metastases. While she had erythrocyte phenotype of blood group A, the signet ring adenocarcinoma cells expressed blood group B incompatible antigenic determinants with lectin/mAb. In the second case, the autopsy of a 78-year-old female resulted in no macroscopic tumor sign except a moderately enlarged, ham hard spleen. Light microscopy revealed adenocarcinomatous infiltration in the splenic sinusoids. The patient had blood group O, while the metastatic cells in the spleen reacted with Breast Carcinoma Antigen (BioGenex) and incompatible anti-B Banderiaeasimplicifolia agglutinin I and anti-B mAb. It proved to be a case of an occult, completely regressed breast cancer. Based on these observations the expression of tumor specific incompatible blood group antigens might occur from time to time, mostly in adenocarcinomas. Accordingly, blood group-based specific immuno-oncotherapy could be considered in some cancer cases.

Three-dimensional models of antigens with serodiagnostic potential for leprosy:An in silico study

BACKGROUND Leprosy is a disease caused by Mycobacterium leprae(M.leprae),an intracellular pathogen that has tropism and affects skin and nervous system cells.The disease has two forms of presentation:Paucibacillary and multibacillary,with different clinical and immunological manifestations.Unlike what occurs in the multibacillary form,the diagnostic tests for the paucibacillary form are nonspecific and not very sensitive,allowing the existence of infected individuals without treatment,which contributes to the spread of the pathogen in the population.To mitigate this contamination,more sensitive diagnostic tests capable of detecting paucibacillary patients are needed.AIM To predict the three-dimensional structure models of M.leprae antigens with serodiagnostic potential for leprosy.METHODS In this in silico study,satisfactory templates were selected in the Protein Data Bank(PDB)using Basic Local Alignment Search Tool to predict the structural templates of ML2038,ML0286,ML0050,and 85B antigens by comparative modeling.The templates were selected according to general criteria such as sequence identity,coverage,X-ray resolution,Global Model Quality Estimate value and phylogenetic relationship;Clustal X 2.1 software was used in this analysis.Molecular modeling was completed using the software Modeller 9v13.Visualization of the models was made using ViewerLite 4.2 and PyMol software,and analysis of the quality of the predicted models was performed using the QMEAN score and Z-score.Finally,the three-dimensional moels were validated using the MolProbity and Verify 3D platforms.RESULTS The three-dimensional structure models of ML2038,ML0286,ML0050,and 85B antigens of M.leprae were predicted using the templates PDB:3UOI(90.51%identity),PDB:3EKL(87.46%identity),PDB:3FAV(40.00%identity),and PDB:1F0N(85.21%identity),respectively.The QMEAN and Z-score values indicated the good quality of the structure models.These data refer to the monomeric units of antigens,since some of these antigens have quaternary structure.The validation of the models was performed with the final three-dimensional structure-monomer(ML0050 and 85B antigens)and quaternary structures(ML2038 and ML0286).The majority of amino acid residues were observed in favorable and allowed regions in the Ramachandran plot,indicating correct positioning of the side chain and absence of steric impediment.The MolProbity score value and Verify 3D results of all models indicated a satisfactory prediction.CONCLUSION The polarized immune response against M.leprae creates a problem in leprosy detection.The selection of immunodominant epitopes is essential for the development of more sensitive serodiagnostic tests,for this it is important to know the three-dimensional structure of the antigens,which can be predicted with bioinformatics tools.

Serum tumor markers (carcinoembryonic antigen, carbohydrate antigen 19-9, carbohydrate antigen 72-4, carbohydrate antigen 24-2, ferritin) and gastric cancer prognosis correlation

BACKGROUND Gastric cancer is a kind of malignant tumor which is prevalent all over the world.Although some progress has been made in the treatment of gastric cancer,its prognosis is still not optimistic,so it is of great significance to find reliable prog-nostic indicators to guide the treatment and management of patients with gastric cancer.AIM To explore the relationship between serum levels of five biomarkers[carcinoem-bryonic antigen(CEA),carbohydrate antigen(CA)19-9,CA72-4,CA24-2,and ferritin]and prognosis in patients with gastric cancer.METHODS This study included 200 patients with gastric adenocarcinoma,and conducted an in-depth analysis of their baseline characteristics,relationship between tumor markers and staging,and prognosis.The study found that CA19-9 has a signi-ficant correlation with tumor stage,the average levels of CA24-2,CEA,CA72-4 and ferritin were slightly increased disregarding the stage of tumor.Survival analysis showed that increases in CEA,CA19-9,CA24-2,and ferritin were all associated with shortened overall survival of patients.Further multivariate ana-lysis revealed that elevated serum CA72-4 levels were an inde-pendent adverse prognostic factor.RESULTS This study reveals that there is a significant correlation between the expression levels of serum tumor markers CEA,CA19-9,CA72-4,CA24-2 and ferritin in patients with gastric cancer and prognosis,and can be used as important indicators for prognostic evaluation of gastric cancer.In particular,markers that appear abnormally elevated initially may help identify gastric cancer patients with poor prognosis.CONCLUSION Serum CEA and CA19-9 play an important role in the prognosis assessment of gastric cancer,and are effective tools to guide clinical practice and optimize individualized treatment strategies for gastric cancer patients.

Recurrence and influencing factors of hepatitis B surface antigen seroclearance induced by peginterferon alpha-based regimens

BACKGROUND The long-term stability of hepatitis B surface antigen(HBsAg)seroclearance following peginterferon alpha(peg-IFN-α)-based therapy has not been extensively studied,leaving the full potential and limitations of this strategy unclear.AIM To assess HBsAg recurrence after seroclearance achieved by peg-IFN-αregimens.METHODS This prospective,multicenter,observational study was conducted from November 2015 to June 2021 at three Chinese hospitals:The Second Affiliated Hospital of Xi’an Jiaotong University,Ankang Central Hospital,and The Affiliated Hospital of Yan’an University.Participants who achieved HBsAg seroclearance following peg-IFN-α-based treatments were monitored every 4-12 weeks post-treatment for hepatitis B virus(HBV)markers,HBV DNA,and liver function.The primary outcome was HBV recurrence,defined as the reemergence of HBsAg,HBV DNA,or both,at least twice within 4-8 weeks of follow-up.RESULTS In total,121 patients who achieved HBsAg seroclearance were enrolled.After a median follow-up of 84.0(48.0,132.0)weeks,four subjects were lost to follow-up.HBsAg recurrence was detected in 16 patients.The cumulative HBsAg recurrence rate in the intention-to-treat population was 15.2%.Multivariate logistic regression analysis demonstrated that consolidation time<12 weeks[odds ratio(OR)=28.044,95%CI:4.525-173.791]and hepatitis B surface antibody disappearance during follow-up(OR=46.445,95%CI:2.571-838.957)were strong predictors of HBsAg recurrence.HBV DNA positivity and decompensation of liver cirrhosis and hepatocellular carcinoma were not observed.CONCLUSION HBsAg seroclearance following peg-IFN-αtreatment was durable over 84 weeks of follow-up with a cumulative recurrence rate of 15.2%.

The combined detection of carcinoembryonic antigen,carcinogenic antigen 125,and carcinogenic antigen 19-9 in colorectal cancer patients

BACKGROUND Hepatic metastases are common and difficult to treat after colorectal cancer(CRC)surgery.The predictive value of carcinoembryonic antigen(CEA),cancer antigen(CA)125 and CA19-9 combined tests for liver metastasis is unclear.AIM To evaluate predictive value of combined tests for CEA,CA125,and CA19-9 levels in patients with liver metastases of CRC.METHODS The retrospective study included patients with CRC alone(50 cases)and patients with CRC combined with liver metastases(50 cases)who were hospitalized between January 2021 and January 2023.Serum CEA,CA125 and CA19-9 levels were compared between the two groups,and binary logistic regression was used to analyze the predictive value of the combination of these tumor markers in liver metastasis.In addition,we performed receiver operating characteristic(ROC)curve analysis to assess its diagnostic accuracy.RESULTS The results showed that the serum CEA,CA125 and CA19-9 levels in the CRC with liver metastasis group were significantly higher than those in the CRC alone group.Specifically,the average serum CEA level in the CRC with liver metastasis group was 162.03±810.01 ng/mL,while that in the CRC alone group was 5.71±9.76 ng/mL;the average serum CA125 levels were 43.47±83.52 U/mL respectively.and 13.5±19.68 U/mL;the average serum CA19-9 levels were 184.46±473.13 U/mL and 26.55±43.96 U/mL respectively.In addition,binary logistic regression analysis showed that CA125 was significant in predicting CRC liver metastasis(P<0.05).ROC curve analysis results showed that the areas under the ROC curves of CEA,CA125 and CA19-9 were 0.607,0.692 and 0.586.CONCLUSION These results suggest that combined detection of these tumor markers may help early detection and intervention of CRC liver metastasis,thereby improving patient prognosis.

Prostate cancer with elevated free prostate-specific antigen density:A case report

BACKGROUND Prostate cancer is the second most common cancer among men worldwide,and prostate-specific antigen(PSA)is often used in clinical practice to screen for prostate cancer.Normal total PSA(tPSA)level initially excludes prostate cancer.Here,we report a case of prostate cancer with elevated free PSA density(fPSAD).CASE SUMMARY A patient diagnosed with benign prostatic hyperplasia underwent prostatectomy,and the postoperative pathological results showed acinar adenocarcinoma of the prostate.The patient is currently undergoing endocrine chemotherapy.CONCLUSION We provide a clinical reference for diagnosis and treatment of patients with normal tPSA but elevated fPSAD.

Human leukocyte antigen compatibility and incidence of donorspecific antibodies in pediatric liver transplant recipients

BACKGROUND Antibody-mediated rejection following liver transplantation(LT)has been increasingly recognized,particularly with respect to the emergence of de novo donor-specific antibodies(DSAs)and their impact on graft longevity.While substantial evidence for adult populations exists,research focusing on pediatric LT outcomes remains limited.AIM To investigate the prevalence of human leukocyte antigen(HLA)mismatches and DSA and evaluate their association with rejection episodes after pediatric LT.METHODS A cohort of pediatric LT recipients underwent HLA testing at Santa Casa de Porto Alegre,Brazil,between December 2013 and December 2023.Only patients who survived for>30 days after LT with at least one DSA analysis were included.DSA classes I and II and cross-matches were analyzed.The presence of de novo DSA(dnDSA)was evaluated at least 3 months after LT using the Luminex®single antigen bead method,with a positive reaction threshold set at 1000 MFI.Rejection episodes were confirmed by liver biopsy.RESULTS Overall,67 transplanted children were analyzed;61 received grafts from living donors,85%of whom were related to recipients.Pre-transplant DSA(class I or II)was detected in 28.3%of patients,and dnDSA was detected in 48.4%.The median time to DSA detection after LT was 19.7[interquartile range(IQR):4.3-35.6]months.Biopsyproven rejection occurred in 13 patients at follow-up,with C4d positivity observed in 5/13 Liver biopsies.The median time to rejection was 7.8(IQR:5.7-12.8)months.The presence of dnDSA was significantly associated with rejection(36%vs 3%,P<0.001).The rejection-free survival rates at 12 and 24 months were 76%vs 100%and 58%vs 95%for patients with dnDSA anti-DQ vs those without,respectively.CONCLUSION Our findings highlight the importance of incorporating DSA assessment into pre-and post-transplantation protocols for pediatric LT recipients.Future implications may include immunosuppression minimization strategies based on this analysis in pediatric LT recipients.

Technetium-99m-methylene diphosphonate single photon emission computed tomography/computed tomography combined with prostate-specific antigen/free prostate-specific antigen ratio for bone metastasis of prostate cancer

BACKGROUND Prostate cancer(PC)is one of the most common malignant tumors in men,and bone metastasis is one of its common complications,which seriously affects the quality of life and prognosis of patients.AIM To investigate the diagnostic value of technetium-99m-methylene diphosphonate(99mTc-MDP)single photon emission computed tomography(SPECT)/CT imaging combined with the serum prostate-specific antigen(PSA)/free PSA ratio for PC bone metastasis(PCBM).METHODS One hundred patients with PC who visited the Hospital of Chengdu University of Traditional Chinese Medicine from January 2020 to January 2022 were recruited as the experimental(Exp)group,while 30 patients with benign prostatic lesions(BPLs)were recruited as the control(Ctrl)group.All patients underwent 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA testing.The SPECT/CT imaging results and serum PSA/fPSA ratios of patients were analyzed to evaluate their diagnostic values for PCBM.RESULTS The difference in general information of the patients was not obvious,showing comparability.The two methods showed no visible differences in negative predictive value and sensitivity for patients with PCBM,but had great differences in positive predictive value and specificity(P<0.05).The PSA/fPSA ratio of patients with PC in the Exp group was lower than those with BPLs,and patients with PCBM had a much lower PSA/fPSA ratio than those without PC(P<0.05).The results confirmed that the combined use of 99mTc-MDP SPECT/CT imaging and serum PSA/fPSA ratio achieved a detection rate of 95%for PCBM.CONCLUSION The combination of 99mTc-MDP SPECT/CT and PSA/fPSA ratio is accurate and reliable for the diagnosis of PCBM,which provides an important reference for clinical practice.

Hepatitis B surface antigen-negative but hepatitis B envelope antigen-positive false occult hepatitis B virus infection:A case report

BACKGROUND Occult hepatitis B infection(OBI)is characterized by the detection of hepatitis B virus(HBV)DNA in serum(usually HBV DNA<200 IU/mL)or the liver but negativity for hepatitis B surface antigen(HBsAg).The diagnosis of OBI relies on the sensitivity of assays used in the detection of HBV DNA and HBsAg.HBsAg assays with inadequate sensitivity or inability to detect HBV S variants may lead to misdiagnosis of OBI in people with overt HBV infection.CASE SUMMARY We report a HBsAg-negative but hepatitis B envelope antigen-positive patient who had a significant HBV DNA level.The patient was initially diagnosed as having OBI.However,sequence analysis revealed a unique insertion of amino acid residues at positions 120-124 in the S protein,which affects the formation of a disulfide bond that is associated with the formation of a loop.It is well known that there is an overlap between the S protein and Pol protein.We found that this new insertion site occurred in polymerase/reverse transcriptase domain,indi-cating that this insertion might be involved in HBV pathogenicity.The patient was finally diagnosed with a false OBI.CONCLUSION An insertion of amino acid residues at positions 120-124 of the S protein affects the formation of immunodominant epitopes and results in negative HBsAg levels.

Antigen epitopes of animal coronaviruses:a mini-review

Coronaviruses are widespread in nature and can infect mammals and poultry,making them a public health concern.Globally,prevention and control of emerging and re-emerging animal coronaviruses is a great challenge.The mecha-nisms of virus-mediated immune responses have important implications for research on virus prevention and control.The antigenic epitope is a chemical group capable of stimulating the production of antibodies or sensitized lympho-cytes,playing an important role in antiviral immune responses.Thus,it can shed light on the development of diagnos-tic methods and novel vaccines.Here,we have reviewed advances in animal coronavirus antigenic epitope research,aiming to provide a reference for the prevention and control of animal and human coronaviruses.

Prediction and analysis of albumin-bilirubin score combined with liver function index and carcinoembryonic antigen on liver metastasis of colorectal cancer

BACKGROUND Colorectal cancer(CRC)is a common malignant tumor,and liver metastasis is one of the main recurrence and metastasis modes that seriously affect patients’survival rate and quality of life.Indicators such as albumin bilirubin(ALBI)score,liver function index,and carcinoembryonic antigen(CEA)have shown some potential in the prediction of liver metastasis but have not been fully explored.AIM To evaluate its predictive value for liver metastasis of CRC by conducting the combined analysis of ALBI,liver function index,and CEA,and to provide a more accurate liver metastasis risk assessment tool for clinical treatment guidance.METHODS This study retrospectively analyzed the clinical data of patients with CRC who received surgical treatment in our hospital from January 2018 to July 2023 and were followed up for 24 months.According to the follow-up results,the enrolled patients were divided into a liver metastasis group and a nonliver metastasis group and randomly divided into a modeling group and a verification group at a ratio of 2:1.The risk factors for liver metastasis in patients with CRC were analyzed,a prediction model was constructed by least absolute shrinkage and selection operator(LASSO)logistic regression,internal validation was performed by the bootstrap method,the reliability of the prediction model was evaluated by subject-work characteristic curves,calibration curves,and clinical decision curves,and a column graph was drawn to show the prediction results.RESULTS Of 130 patients were enrolled in the modeling group and 65 patients were enrolled in the verification group out of the 195 patients with CRC who fulfilled the inclusion and exclusion criteria.Through LASSO regression variable screening and logistic regression analysis.The ALBI score,alanine aminotransferase(ALT),and CEA were found to be independent predictors of liver metastases in CRC patients[odds ratio(OR)=8.062,95%confidence interval(CI):2.545-25.540],(OR=1.037,95%CI:1.004-1.071)and(OR=1.025,95%CI:1.008-1.043).The area under the receiver operating characteristic curve(AUC)for the combined prediction of CRLM in the modeling group was 0.921,with a sensitivity of 78.0%and a specificity of 95.0%.The H-index was 0.921,and the H-L fit curve hadχ^(2)=0.851,a P value of 0.654,and a slope of the calibration curve approaching 1.This indicates that the model is extremely accurate,and the clinical decision curve demonstrates that it can be applied effectively in the real world.We conducted internal verification of one thousand resamplings of the modeling group data using the bootstrap method.The AUC was 0.913,while the accuracy was 0.869 and the kappa consistency was 0.709.The combination prediction of liver metastasis in patients with CRC in the verification group had an AUC of 0.918,sensitivity of 85.0%,specificity of 95.6%,C-index of 0.918,and an H-L fitting curve withχ^(2)=0.586,P=0.746.CONCLUSION The ALBI score,ALT level,and CEA level have a certain value in predicting liver metastasis in patients with CRC.These three criteria exhibit a high level of efficacy in forecasting liver metastases in patients diagnosed with CRC.The risk prediction model developed in this work shows great potential for practical application.

Proliferating cell nuclear antigen of Ulva prolifera is involved in the response to temperature stress

Ulva prolifera is the most common specie causative to green tide,and its growth is sensitive to temperature stress.However,the mechanisms of U.prolifera response to temperature stress remain elusive.In this study,high temperature(36℃)stimulus promoted the death of unformed cell wall protoplasts and delayed the division of formed cell wall protoplasts,while low-temperature(4℃)stimulus did not,suggesting that the mechanisms of the response of U.prolifera to high and low temperature stresses are different.Transcriptome results show that proliferation-related genes were differentially expressed under high and low-temperature stresses,especially the proliferating cell nuclear antigen(PCNA)and cyclins(CYCs).Subsequently,the interaction between PCNA and Cyclin A was confirmed by Co-immunoprecipitation,yeast two-hybrid,and so on.Furthermore,high-and low temperature stresses induced the expression of PCNA and Cyclin A in varying of degrees,and activated extracellular signal-regulated kinase(ERK)signal pathway.These results suggest,PCNA,Cyclin A,and ERK signal pathway played important roles in the resistance of U.prolifera to temperature stress.Interestingly,high-temperature stress induced an increase of miR-2916 in abundance,and exhibiting reverse expression of PCNA;and PCNA was target gene of miR-2916,suggesting that miR-2916 protected U.prolifera from high-temperature stress via post-transcriptionally regulation of PCNA.This study laid a foundation for understanding the function of PCNA and Cyclin A,moreover,it has a guiding significance to explore the mechanisms of the response to temperature stress from proliferation-related genes regulatory networks in U.prolifera.

Establishment and performance analysis of a new multiplex detection method for influenza an and B virus antigen

BACKGROUND Influenza A and B virus detection is pivotal in epidemiological surveillance and disease management.Rapid and accurate diagnostic techniques are crucial for timely clinical intervention and outbreak prevention.Quantum dot-encoded microspheres have been widely used in immunodetection.The integration of quantum dot-encoded microspheres with flow cytometry is a well-established technique that enables rapid analysis.Thus,establishing a multiplex detection method for influenza A and B virus antigens based on flow cytometry quantum dot microspheres will help in disease diagnosis.AIM To establish a codetection method of influenza A and B virus antigens based on flow cytometry quantum dot-encoded microsphere technology,which forms the foundation for the assays of multiple respiratory virus biomarkers.METHODS Different quantum dot-encoded microspheres were used to couple the monoclonal antibodies against influenza A and B.The known influenza A and B antigens were detected both separately and simultaneously on a flow cytometer,and the detection conditions were optimized to establish the influenza A and B antigen codetection method,which was utilized for their detection in clinical samples.The results were compared with the fluorescence quantitative polymerase chain reaction(PCR)method to validate the clinical performance of this method.RESULTS The limits of detection of this method were 26.1 and 10.7 pg/mL for influenza A and B antigens,respectively,which both ranged from 15.6 to 250000 pg/mL.In the clinical sample evaluation,the proposed method well correlated with the fluorescent quantitative PCR method,with positive,negative,and overall compliance rates of 57.4%,100%,and 71.6%,respectively.CONCLUSION A multiplex assay for quantitative detection of influenza A and B virus antigens has been established,which is characterized by high sensitivity,good specificity,and a wide detection range and is promising for clinical applications.