Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study desi...Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba location.Stool specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine specimens.Participants’sociodemographic details were obtained using a standardized questionnaire.Results:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 mL.The patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,respectively.Women without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a latrine.Similarly,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary schistosomiasis.In bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.展开更多
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 ...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.展开更多
Introduction and Objectives: Soil-Transmitted-Helminthiasis (STH) is a public health problem in Cameroon. The control strategies currently in place, particularly chemoprevention, has shortcomings linked to the target ...Introduction and Objectives: Soil-Transmitted-Helminthiasis (STH) is a public health problem in Cameroon. The control strategies currently in place, particularly chemoprevention, has shortcomings linked to the target population, which are school-age children. The objective was to determine the prevalence and the risk factors associated with geo-helminthiasis in children aged 0 to 3 years in a rural health district. Method: From December 2020 to May 2021, a descriptive and analytical cross-sectional study of 376 children between 6 and 36 months was carried out in the Akonolinga health district. This was a cluster sampling in 4 health areas. Stool samples were collected and analysed using the mini-FLOTAC method. The results expressed as the number of eggs per gram of stool. A questionnaire on socio-demographic and lifestyle data was administered to the parents. The Chi-squared test was used to measure the association between geo-helminth infection and the data collected. A multivariate analysis using logistic regression was performed (p 0.05). Results: The prevalence of STH was 19.4% (Ascaris lumbricoides: 16% and Trichuris trichiura: 8%). Risk factors were: consumption of contaminated water (AOR = 1.93 [1.03 - 3.6];p = 0.040), early contact of the child with the ground (before age of 4 months) (AOR = 4.9 [2.1 - 11.37];p .001), habit of walking barefoot (AOR = 2.91 [1.1 - 7.97];p = 0.038), and living in a habitat with unpaved ground (AOR = 7.4 [1.55 - 35.7];p = 0.012). Conclusion: The prevalence of STHs in infants was high. Preventive chemotherapy should be extended to this age-group, and other measures intensified.展开更多
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 aci...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.展开更多
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 ad...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.展开更多
Introduction: Soil-transmitted helminthic infection (STHI) is a common public health challenge of children in the most deprived communities in low income countries. In the long-term, STHI can cause developmental and g...Introduction: Soil-transmitted helminthic infection (STHI) is a common public health challenge of children in the most deprived communities in low income countries. In the long-term, STHI can cause developmental and growth disorders leading to future learning defect. Objective: Our aim was to determine the prevalence and pattern of soil-transmitted helminthic infection among children attending a tertiary hospital in Imo State, Nigeria. Patients and Method: The study involved a cross-sectional survey of 268 children, aged 7 months to 18 years seen in a tertiary health facility in Nigeria;from August to December 2022. Data were collected using a structured questionnaire and stool samples were analyzed for intestinal helminths using the Kato-Katz method. Results: The prevalence of soil-transmitted helminthic infection (STHI) was 38.4%. Of all STHIs, Ascaris lumbricoides was the commonest geohelminth observed, 81 (62.1%). Multiple infections were noted in 25 (62.4%) of the specimen. The prevalence of soil-transmitted helminthic infection amongst subjects’ 5 - 9 years was high and least in children older than 15 years. This difference was not statistically significant (p = 0.3407). Statistically significant relationship was detected between STHI and low socioeconomic class. Conclusion: The high prevalence rate of soil-transmitted helminthic infection amongst the subjects is disturbing. This high rate justifies strengthening a structured and routine deworming amongst children in order to improve outcome.展开更多
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 sui...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.展开更多
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 glycosyltrans...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.展开更多
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 an...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.展开更多
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 gener...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.展开更多
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,late...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.展开更多
Cancer testis antigens(CTAs)are attractive targets for tumor imm unotherapy because of their tumor specific expression,Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a...Cancer testis antigens(CTAs)are attractive targets for tumor imm unotherapy because of their tumor specific expression,Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.展开更多
Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hyp...Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.展开更多
AIM To explore the etiology and pathogenesis of human primary intrahepatic cholangiocarcinoma, the expression of HBV genes and HBV-antigens was detected in the cancerous tissue and its surrounding hepatic tissues.METH...AIM To explore the etiology and pathogenesis of human primary intrahepatic cholangiocarcinoma, the expression of HBV genes and HBV-antigens was detected in the cancerous tissue and its surrounding hepatic tissues.METHODS HBV-antigens were detected by immunohistochemical technique and HBV genes were examined with in situ hybridization.RESULTS In 20 cases of cholangiocarcinoma, the positive detection rate of HBxAg, pre-S1, pre-S2, HBsAg and HBcAg was 75%, 40%, 40%, 10% and 0%, respectively, and in the surrounding hepatic tissues of 19 cases the positive rates were 84.2%, 47.9%, 47.9%, 31.6% and 31.6%. Among 40 cases of cholangiocarcinoma, the positive rate of HBV-DNA, x gene, pre-s gene, s gene and s gene fell on 77.5%, 70.0%, 47.5%, 40% and 42.5%, respectively, and of the surrounding hepatic tissues in 33 cases, 87.9%, 84.8%, 63.6%, 69.7% and 66.7%.CONCLUSION The development of human primary intrahepatic cholangiocarcinoma bears a close relationship with chronic persistent HBV infection. Particularly, the x gene of HBV and its protein (HBxAg) might play an important role in pathogenesis of hepatic carcinoma.A large number of studies indicate a close relationship between human primary hepatocellular carcinoma and hepatitis B virus (HBV) infection, which is considered generally as an important factor in the development of hepatic carcinoma[1,2]. In human primary hepatic carcinoma, hepatocellular carcinoma is more frequently encountered, while intrahepatic cholangiocarcinoma (ChC), including hepatocholangiocarcinoma (HChC), is relatively less, being 8%-10%[3]. For a long time, the etiology and pathogenesis of intrahepatic cholangiocarcinoma have been unclear. A few reports considered it to be related to infestation with clonorchiasis sinensis[4,5], but never involved with HBV infection. We used immunohistochemical technique and in situ hybridization methods to detect HBV genes and their -related antigens in the tissues of intrahepatic cholangiocarcinoma and its surrounding hepatic tissues for the purpose of exploring the etiology and pathogenesis of intrahepatic cholangiocarcinoma.展开更多
Objective:To determine the prevalence of intestinal parasitic infections and soil-transmitted helminths(STHs) among primary schoolchildren in El dhayga,Central Sudan.Methods:In this cross-sectional study,three fresh f...Objective:To determine the prevalence of intestinal parasitic infections and soil-transmitted helminths(STHs) among primary schoolchildren in El dhayga,Central Sudan.Methods:In this cross-sectional study,three fresh faecal samples were collected from each child,which were examined by direct wet mount,brine flotation,formalin-ether and Kato-Katz techniques.The intensity of each STH infection was expressed as the mean of eggs per gram counts of the three samples.Results:In total,142(90.4%) of 157 children harboured at least one type of intestinal parasite.Ascaris lumbricoides,Hymenolepis nana,Entamoeba histolytica and Giardia lamblia were the most common parasites found,with prevalence rates of 32.5%,30.6%,33.1%and 19.7%,respectively.Out of these 157 children,29(18.5%) harboured more than two intestinal parasitic infections.No cases of Schistosoma mansoni or Enterobius vermicularis were identified. Conclusions:The study demonstrates significant burden of intestinal protozoa and STH infections in this part of Sudan and highlights the need for preventive and intervention measures.展开更多
BACKGROUND The bacteria Campylobacter jejuni(C. jejuni) is commonly associated with GuillaneBarré syndrome(GBS) and irritable bowel syndrome(IBS), but studies have also linked it with Miller Fisher syndrome, reac...BACKGROUND The bacteria Campylobacter jejuni(C. jejuni) is commonly associated with GuillaneBarré syndrome(GBS) and irritable bowel syndrome(IBS), but studies have also linked it with Miller Fisher syndrome, reactive arthritis and other disorders, some of which are autoimmune. It is possible that C. jejuni and its toxins may be crossreactive with some human tissues and food antigens, potentially leading to autoimmune responses.AIM To measure the immune reactivity of C. jejuni and C. jejuni cytolethal distending toxin(Cdt) antibodies with tissue and food antigens to examine their role in autoimmunities.METHODS Using enzyme-linked immunosorbent assay(ELISA) methodology, specific antibodies made against C. jejuni and C. jejuni Cdt were applied to a variety of microwell plates coated with 45 tissues and 180 food antigens. The resulting immunoreactivities were compared to reactions with control wells coated with human serum albumin(HSA) which were used as negative controls and with wells coated with C. jejuni lysate or C. jejuni Cdt which served as positive controls.RESULTS At 3 SD above the mean of control wells coated with HSA or 0.41 OD, the mouse monoclonal antibody made against C. jejuni showed moderate to high reactions with zonulin, somatotropin, acetylcholine receptor, β-amyloid and presenilin.This immune reaction was low with an additional 25 tissue antigens including asialoganglioside, and the same antibody did not react at all with another 15 tissue antigens. Examining the reaction between C. jejuni antibody and 180 food antigens, we found insignificant reactions with 163 foods but low to high immune reactions with 17 food antigens. Similarly, we examined the reaction of C. jejuni Cdt with the same tissues and food antigens. The strongest reactions were observed with zonulin, intrinsic factor and somatotropin. The reaction was moderate with 9 different tissue antigens including thyroid peroxidase, and reaction was low with another 10 different antigens, including neuronal antigens.The reaction of C. jejuni Cdt antibody with an additional 23 tissue antigens was insignificant. Regarding the reaction of C. jejuni Cdt antibody with different food antigens, 160 out of 180 foods showed insignificant reactions, while 20 foods showed reactions ranging from low to high.CONCLUSION Our findings indicate that C. jejuni and its Cdt may play a role in inflammation and autoimmunities beyond the gut.展开更多
The introduction of serum prostate-specific antigen (PSA) in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in over...The introduction of serum prostate-specific antigen (PSA) in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens (CTAs) are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.展开更多
Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. T...Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.展开更多
Evidence from epidemiological studies indicates an inverse correlation between the incidence of certain immune-mediated diseases, including inflammatory bowel diseases (IBD), and exposure to helminths. Helminth parasi...Evidence from epidemiological studies indicates an inverse correlation between the incidence of certain immune-mediated diseases, including inflammatory bowel diseases (IBD), and exposure to helminths. Helminth parasites are the classic inducers of Th2 responses. The Th2-polarized T cell response driven by helminth infection has been linked to the attenuation of some damaging Th1 driven inflammatory responses, preventing some Th1-mediated autoimmune diseases in the host, including experimentally induced colitis. Helminth parasites (the porcine whipworm, Trichuris suis ) have been tested for treating IBD patients, resulting in clinical amelioration of the disease. As a result, there is a great deal of interest in the research community in exploring the therapeutic use of helminth parasites for the control of immune-mediated diseases, including IBD. However, recent studies have provided evidence indicating the exacerbating effects of helminths on bacterial as well as non-infectious colitis in animal models. Therefore, a better understanding of mechanisms by which helminths modulate host immune responses in the gut may reveal novel, more effective and safer approaches to helminth-based therapy of IBD.展开更多
Objective: To evaluate the antioxidant activities and phytochemical content of the leaf and root extracts of Rumex crispus using the solvents extraction; methanol extract,ethanol extract, acetone extract(ACE), and wat...Objective: To evaluate the antioxidant activities and phytochemical content of the leaf and root extracts of Rumex crispus using the solvents extraction; methanol extract,ethanol extract, acetone extract(ACE), and water extract.Methods: Total flavonoids content, total phenolic content, and total proanthocyanidin were evaluated using spectrophotometric equivalents of the standards, quercetin, gallic acid and catechin respectively. The antioxidant activities of the plant extracts were determined using ABTS, DPPH, ferric reducing antioxidant power, total antioxidant capacity and nitric oxide scavenging assays.Results: The flavonoids and phenols contents of the extracts were in the range of(19.39 ± 4.08) to(526.23 ± 17.52) mg QE/g and(16.95 ± 12.03) to(240.68 ± 3.50) mg GAE/g, respectively. ACE of the leaf has the highest value of total flavonoids content(526.23 ± 17.52) mg QE/g while ACE of the root has the highest value of total phenolic content(240.68 ± 3.50) mg GAE/g. The highest content of total proanthocyanidin(645.38 ± 1.33) mg CE/g was in ACE of the root. Significant amounts of saponin and alkaloid were also present in the root and leaf extracts. All solvent fractions showed significant antioxidant activities(P < 0.05) with ACE of the root having the highest scavenging value as shown in DPPH, ABTS, total antioxidant capacity, nitric oxide and ferric reducing antioxidant power(IC50= 0.014 mg/m L, <0.005 mg/m L, 0.048 mg/m L,0.067 mg/m L, and 0.075 mg/m L, respectively).Conclusions: In this study, the mean phytochemical content of the root of Rumex crispus is higher than that of the leaf and this may have contributed to its high antioxidant activities. This may also justify the frequent use of the root more than the leaves in traditional medicine for the cure of helminthic infections.展开更多
文摘Objective:To assess the epidemiology of urinary schistosomiasis and soil-transmitted helminthiasis among women of reproductive age in Mwaluphamba,Kwale County,Kenya.Methods:A community-based cross-sectional study design was employed to randomly sample 422 women of reproductive age(15-<50 years)from four villages in Mwaluphamba location.Stool specimens were collected and examined using the Kato-Katz method,while filtration technique was used to analyze urine specimens.Participants’sociodemographic details were obtained using a standardized questionnaire.Results:Urinary schistosomiasis prevalence was at 4.7%(20/422,95%CI 2.8%-6.9%)while the prevalence of soil-transmitted helminthiasis infection was 4.5%(19/422,95%CI 2.6%-6.7%).The infection intensities of urinary schistosomiasis among the study participants ranged from 1 to 120 eggs/10 mL of urine with median egg count of 18.45 eggs/10 mL.The patients were diagnosed with light infection,of 56.16 egg/gram and 48.48 egg/gram for Trichuris trichiura and hookworms,respectively.Women without latrines had 15.7 times higher risk of having urinary schistosomiasis compared to those with a latrine.Similarly,use of surface water(aOR=1.0,95%CI 0.2-1.4,P=0.010)and crossing the river to go to a place(aOR=1.1,95%CI 0.3-1.6,P=0.009)were statistically significant risk factors for getting urinary schistosomiasis.In bivariable regression analysis,defecating around the water source(OR=4.3,95%CI 1.5-12.9)had a statistically significant association with the prevalence of soil-transmitted helminthiasis(P=0.008).Conclusions:This study has given an insight on the prevalence and intensity of urinary schistosomiasis and soil-transmitted helminthiasis in Mwaluphamba location that form a basis for strengthening the control and elimination programmes for these neglected tropical diseases.
基金the National Natural Science Foundation of China,No.82273457the Natural Science Foundation of Guangdong Province,No.2021A1515012180,2023A1515012762 and No.2019A1515010962+1 种基金Special Grant for Key Area Programs of Guangdong Department of Education,No.2021ZDZX2040Science and Technology Special Project of Guangdong Province,No.210715216902829.
文摘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.
文摘Introduction and Objectives: Soil-Transmitted-Helminthiasis (STH) is a public health problem in Cameroon. The control strategies currently in place, particularly chemoprevention, has shortcomings linked to the target population, which are school-age children. The objective was to determine the prevalence and the risk factors associated with geo-helminthiasis in children aged 0 to 3 years in a rural health district. Method: From December 2020 to May 2021, a descriptive and analytical cross-sectional study of 376 children between 6 and 36 months was carried out in the Akonolinga health district. This was a cluster sampling in 4 health areas. Stool samples were collected and analysed using the mini-FLOTAC method. The results expressed as the number of eggs per gram of stool. A questionnaire on socio-demographic and lifestyle data was administered to the parents. The Chi-squared test was used to measure the association between geo-helminth infection and the data collected. A multivariate analysis using logistic regression was performed (p 0.05). Results: The prevalence of STH was 19.4% (Ascaris lumbricoides: 16% and Trichuris trichiura: 8%). Risk factors were: consumption of contaminated water (AOR = 1.93 [1.03 - 3.6];p = 0.040), early contact of the child with the ground (before age of 4 months) (AOR = 4.9 [2.1 - 11.37];p .001), habit of walking barefoot (AOR = 2.91 [1.1 - 7.97];p = 0.038), and living in a habitat with unpaved ground (AOR = 7.4 [1.55 - 35.7];p = 0.012). Conclusion: The prevalence of STHs in infants was high. Preventive chemotherapy should be extended to this age-group, and other measures intensified.
文摘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.
文摘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.
文摘Introduction: Soil-transmitted helminthic infection (STHI) is a common public health challenge of children in the most deprived communities in low income countries. In the long-term, STHI can cause developmental and growth disorders leading to future learning defect. Objective: Our aim was to determine the prevalence and pattern of soil-transmitted helminthic infection among children attending a tertiary hospital in Imo State, Nigeria. Patients and Method: The study involved a cross-sectional survey of 268 children, aged 7 months to 18 years seen in a tertiary health facility in Nigeria;from August to December 2022. Data were collected using a structured questionnaire and stool samples were analyzed for intestinal helminths using the Kato-Katz method. Results: The prevalence of soil-transmitted helminthic infection (STHI) was 38.4%. Of all STHIs, Ascaris lumbricoides was the commonest geohelminth observed, 81 (62.1%). Multiple infections were noted in 25 (62.4%) of the specimen. The prevalence of soil-transmitted helminthic infection amongst subjects’ 5 - 9 years was high and least in children older than 15 years. This difference was not statistically significant (p = 0.3407). Statistically significant relationship was detected between STHI and low socioeconomic class. Conclusion: The high prevalence rate of soil-transmitted helminthic infection amongst the subjects is disturbing. This high rate justifies strengthening a structured and routine deworming amongst children in order to improve outcome.
文摘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.
文摘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.
文摘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.
基金This research was supported by the Clinical Frontier Technology Program of the First Affiliated Hospital of Jinan University,China(No.JNU1AF-CFTP-2022-a01223)Natural Science Foundation of Guangdong Province(2019A1515011763,2020A1515110639,2021A1515010994,2022A1515011695)Guangzhou Science and Technology Plan City-School Joint Funding Project(202201020084,202201020065).
文摘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.
基金Supported by the Key Discipline of Jiaxing Respiratory Medicine Construction Project,No.2019-zc-04.
文摘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.
文摘Cancer testis antigens(CTAs)are attractive targets for tumor imm unotherapy because of their tumor specific expression,Since more than half of confirmed CTAs are located on the X-chromosome,we asked whether there is a link between CTA expression and X-chromosomes.Recent reports have shown that reactivation of the inactive X-chromosome,known as X-chromosome reactivation(XCR),a unique phenomenon that exists in many high-risk tumors in women,can transform the expression of many X-linked genes from monoallelic to biallelic.
基金Supported by Ministerium für Wirtschaft,Arbeit und Gesundheit Mecklenburg-Vorpommern,No.TBI-V-1-241-VBW-084
文摘Therapeutic options for the treatment of colorectal cancer(CRC) are diverse but still not always satisfying. Recent success of immune checkpoint inhibition treatment for the subgroup of CRC patients suffering from hypermutated tumors suggests a permanent role of immune therapy in the clinical management of CRC. Substantial improvement in treatment outcome could be achieved by development of efficient patient-individual CRC vaccination strategies. This mini-review summarizes the current knowledge on the two general classes of targets: tumor-associated antigens(TAAs) and tumorspecific antigens. TAAs like carcinoembryonic antigen and melanoma associated antigen are present in and shared by a subgroup of patients and a variety of clinical studies examined the efficacy of different TAA-derived peptide vaccines. Combinations of several TAAs as the next step and the development of personalized TAA-based peptide vaccines are discussed. Improvements of peptidebased vaccines achievable by adjuvants and immunestimulatory chemotherapeutics are highlighted. Finally, we sum up clinical studies using tumor-specific antigens-in CRC almost exclusively neoantigens-which revealed promising results; particularly no severe adverse events were reported so far. Critical progress for clinical outcomes can be expected by individualizing neoantigen-based peptide vaccines and combining them with immunestimulatory chemotherapeutics and immune checkpoint inhibitors. In light of these data and latest developments, truly personalized neoantigen-based peptide vaccines can be expected to fulfill modern precision medicine's requirements and will manifest as treatment pillar for routine clinical management of CRC.
文摘AIM To explore the etiology and pathogenesis of human primary intrahepatic cholangiocarcinoma, the expression of HBV genes and HBV-antigens was detected in the cancerous tissue and its surrounding hepatic tissues.METHODS HBV-antigens were detected by immunohistochemical technique and HBV genes were examined with in situ hybridization.RESULTS In 20 cases of cholangiocarcinoma, the positive detection rate of HBxAg, pre-S1, pre-S2, HBsAg and HBcAg was 75%, 40%, 40%, 10% and 0%, respectively, and in the surrounding hepatic tissues of 19 cases the positive rates were 84.2%, 47.9%, 47.9%, 31.6% and 31.6%. Among 40 cases of cholangiocarcinoma, the positive rate of HBV-DNA, x gene, pre-s gene, s gene and s gene fell on 77.5%, 70.0%, 47.5%, 40% and 42.5%, respectively, and of the surrounding hepatic tissues in 33 cases, 87.9%, 84.8%, 63.6%, 69.7% and 66.7%.CONCLUSION The development of human primary intrahepatic cholangiocarcinoma bears a close relationship with chronic persistent HBV infection. Particularly, the x gene of HBV and its protein (HBxAg) might play an important role in pathogenesis of hepatic carcinoma.A large number of studies indicate a close relationship between human primary hepatocellular carcinoma and hepatitis B virus (HBV) infection, which is considered generally as an important factor in the development of hepatic carcinoma[1,2]. In human primary hepatic carcinoma, hepatocellular carcinoma is more frequently encountered, while intrahepatic cholangiocarcinoma (ChC), including hepatocholangiocarcinoma (HChC), is relatively less, being 8%-10%[3]. For a long time, the etiology and pathogenesis of intrahepatic cholangiocarcinoma have been unclear. A few reports considered it to be related to infestation with clonorchiasis sinensis[4,5], but never involved with HBV infection. We used immunohistochemical technique and in situ hybridization methods to detect HBV genes and their -related antigens in the tissues of intrahepatic cholangiocarcinoma and its surrounding hepatic tissues for the purpose of exploring the etiology and pathogenesis of intrahepatic cholangiocarcinoma.
文摘Objective:To determine the prevalence of intestinal parasitic infections and soil-transmitted helminths(STHs) among primary schoolchildren in El dhayga,Central Sudan.Methods:In this cross-sectional study,three fresh faecal samples were collected from each child,which were examined by direct wet mount,brine flotation,formalin-ether and Kato-Katz techniques.The intensity of each STH infection was expressed as the mean of eggs per gram counts of the three samples.Results:In total,142(90.4%) of 157 children harboured at least one type of intestinal parasite.Ascaris lumbricoides,Hymenolepis nana,Entamoeba histolytica and Giardia lamblia were the most common parasites found,with prevalence rates of 32.5%,30.6%,33.1%and 19.7%,respectively.Out of these 157 children,29(18.5%) harboured more than two intestinal parasitic infections.No cases of Schistosoma mansoni or Enterobius vermicularis were identified. Conclusions:The study demonstrates significant burden of intestinal protozoa and STH infections in this part of Sudan and highlights the need for preventive and intervention measures.
文摘BACKGROUND The bacteria Campylobacter jejuni(C. jejuni) is commonly associated with GuillaneBarré syndrome(GBS) and irritable bowel syndrome(IBS), but studies have also linked it with Miller Fisher syndrome, reactive arthritis and other disorders, some of which are autoimmune. It is possible that C. jejuni and its toxins may be crossreactive with some human tissues and food antigens, potentially leading to autoimmune responses.AIM To measure the immune reactivity of C. jejuni and C. jejuni cytolethal distending toxin(Cdt) antibodies with tissue and food antigens to examine their role in autoimmunities.METHODS Using enzyme-linked immunosorbent assay(ELISA) methodology, specific antibodies made against C. jejuni and C. jejuni Cdt were applied to a variety of microwell plates coated with 45 tissues and 180 food antigens. The resulting immunoreactivities were compared to reactions with control wells coated with human serum albumin(HSA) which were used as negative controls and with wells coated with C. jejuni lysate or C. jejuni Cdt which served as positive controls.RESULTS At 3 SD above the mean of control wells coated with HSA or 0.41 OD, the mouse monoclonal antibody made against C. jejuni showed moderate to high reactions with zonulin, somatotropin, acetylcholine receptor, β-amyloid and presenilin.This immune reaction was low with an additional 25 tissue antigens including asialoganglioside, and the same antibody did not react at all with another 15 tissue antigens. Examining the reaction between C. jejuni antibody and 180 food antigens, we found insignificant reactions with 163 foods but low to high immune reactions with 17 food antigens. Similarly, we examined the reaction of C. jejuni Cdt with the same tissues and food antigens. The strongest reactions were observed with zonulin, intrinsic factor and somatotropin. The reaction was moderate with 9 different tissue antigens including thyroid peroxidase, and reaction was low with another 10 different antigens, including neuronal antigens.The reaction of C. jejuni Cdt antibody with an additional 23 tissue antigens was insignificant. Regarding the reaction of C. jejuni Cdt antibody with different food antigens, 160 out of 180 foods showed insignificant reactions, while 20 foods showed reactions ranging from low to high.CONCLUSION Our findings indicate that C. jejuni and its Cdt may play a role in inflammation and autoimmunities beyond the gut.
文摘The introduction of serum prostate-specific antigen (PSA) in the 1980s has dramatically altered and benefited the initial diagnosis of prostate cancer. However, the widespread use of PSA testing has resulted in overdetection and overtreatment of potentially indolent disease. Thus, a clinical dilemma today in the management of prostate cancer is to discern men with aggressive disease who need definitive treatment from men whose disease are not lethal. Although several serum and tissue biomarkers have been evaluated during the past decade, improved markers are still needed to enhance the accuracy, with which patients at risk can be discerned and treated more aggressively. The cancer/testis antigens (CTAs) are a group of proteins that are restricted to the testis in the normal adult, but are aberrantly expressed in several types of cancers. Because of their restricted expression pattern, the CTAs represent attractive biomarker candidates for cancer diagnosis/prognosis. Furthermore, several studies to date have reported the differential expression of CTAs in prostate cancer. Here, we review recent developments that demonstrate the potential of the CTAs as biomarkers to discern the a^ressive Dhenotvoe of orostate cancer.
基金Indo-UK Cancer Research ProgramNo.BT/IN/UK/NII/2006+3 种基金Centre for Molecular MedicineNo.BT/PR/14549/MED/14/1291NII-core funding,Department of BiotechnologyGovernment of India
文摘Colorectal cancer ranks third among the estimatedcancer cases and cancer related mortalities in United States in 2014. Early detection and efficient therapy remains a significant clinical challenge for this disease. Therefore, there is a need to identify novel tumor asso-ciated molecules to target for biomarker development and immunotherapy. In this regard, cancer testis antigens have emerged as a potential targets for developing novel clinical biomarkers and immunotherapy for various malignancies. These germ cell specific proteins exhibit aberrant expression in cancer cells and contribute in tumorigenesis. Owing to their unique expression profile and immunogenicity in cancer patients, cancer testis antigens are clinically referred as the most promising tumor associated antigens. Several cancer testis antigens have been studied in colorectal cancer but none of them could be used in clinical practice. This review is an attempt to address the promising cancer testis antigens in colorectal cancer and their possible clinical implications as biomarkers and immunotherapeutic targets with particular focus on challenges and future interventions.
基金Grant DK 074727 (R21) from the National Institutes of HealthAn unrestricted educational grant from Wyeth NutritionA research fellowship from the Research Center for High Altitude Medicine, Qinghai University Medical School, China
文摘Evidence from epidemiological studies indicates an inverse correlation between the incidence of certain immune-mediated diseases, including inflammatory bowel diseases (IBD), and exposure to helminths. Helminth parasites are the classic inducers of Th2 responses. The Th2-polarized T cell response driven by helminth infection has been linked to the attenuation of some damaging Th1 driven inflammatory responses, preventing some Th1-mediated autoimmune diseases in the host, including experimentally induced colitis. Helminth parasites (the porcine whipworm, Trichuris suis ) have been tested for treating IBD patients, resulting in clinical amelioration of the disease. As a result, there is a great deal of interest in the research community in exploring the therapeutic use of helminth parasites for the control of immune-mediated diseases, including IBD. However, recent studies have provided evidence indicating the exacerbating effects of helminths on bacterial as well as non-infectious colitis in animal models. Therefore, a better understanding of mechanisms by which helminths modulate host immune responses in the gut may reveal novel, more effective and safer approaches to helminth-based therapy of IBD.
文摘Objective: To evaluate the antioxidant activities and phytochemical content of the leaf and root extracts of Rumex crispus using the solvents extraction; methanol extract,ethanol extract, acetone extract(ACE), and water extract.Methods: Total flavonoids content, total phenolic content, and total proanthocyanidin were evaluated using spectrophotometric equivalents of the standards, quercetin, gallic acid and catechin respectively. The antioxidant activities of the plant extracts were determined using ABTS, DPPH, ferric reducing antioxidant power, total antioxidant capacity and nitric oxide scavenging assays.Results: The flavonoids and phenols contents of the extracts were in the range of(19.39 ± 4.08) to(526.23 ± 17.52) mg QE/g and(16.95 ± 12.03) to(240.68 ± 3.50) mg GAE/g, respectively. ACE of the leaf has the highest value of total flavonoids content(526.23 ± 17.52) mg QE/g while ACE of the root has the highest value of total phenolic content(240.68 ± 3.50) mg GAE/g. The highest content of total proanthocyanidin(645.38 ± 1.33) mg CE/g was in ACE of the root. Significant amounts of saponin and alkaloid were also present in the root and leaf extracts. All solvent fractions showed significant antioxidant activities(P < 0.05) with ACE of the root having the highest scavenging value as shown in DPPH, ABTS, total antioxidant capacity, nitric oxide and ferric reducing antioxidant power(IC50= 0.014 mg/m L, <0.005 mg/m L, 0.048 mg/m L,0.067 mg/m L, and 0.075 mg/m L, respectively).Conclusions: In this study, the mean phytochemical content of the root of Rumex crispus is higher than that of the leaf and this may have contributed to its high antioxidant activities. This may also justify the frequent use of the root more than the leaves in traditional medicine for the cure of helminthic infections.