Plasma-based proteomic profiling identifies the distinct regulation of proteins in hyperplasia and endometrial cancer.

BACKGROUND: Among gynaecological malignancies, endometrial cancer (EC) is the most prevalent type of uterine cancer affecting women. This study explored the proteomic profiles of plasma samples obtained from EC patients, those with hyperplasia (Hy), and a control group (CO). A combination of techniques, such as 2D-DIGE, mass spectrometry, and bioinformatics, including pathway analysis, was used to identify proteins with modified expression levels, biomarkers and their associated metabolic pathways in these groups. METHODS: Thirty-four patients, categorized into three groups-10 with EC, 12 with Hy, and 12 CO-between the ages of 46 and 75 years old were included in the study. Untargeted proteomic analysis was carried out using two-dimensional difference in gel electrophoresis (2D-DIGE) coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). RESULTS: In all three groups, 114 proteins that were significantly (p ≤ 0.05 and fold change ≥ 1.5) altered were successfully identified using peptide mass fingerprints (PMFs). Compared with those in the control group (CO), the EC samples had 85 differentially expressed proteins (39 upregulated and 46 downregulated), and in the Hy group, 81 proteins were dysregulated (40 upregulated and 41 downregulated) compared to those in the CO group, while 33 proteins exhibited differential regulation (12 upregulated and 21 downregulated) in the EC plasma samples compared to those in the Hy group. Vitamin D binding protein and complement C3 distinguished Hy and EC from CO with the greatest changes in expression. Among the differentially expressed proteins identified, enzymes with catalytic activity represented the largest group (42.9%). In terms of biological processes, most of the proteins were involved in cellular processes (28.8%), followed by metabolic processes (16.7%). STRING analysis for protein interactions revealed that the significantly differentially abundant proteins in the three groups are involved in three main biological processes: signalling of complement and coagulation cascades, regulation of insulin-like growth factor (IGF) transport and uptake by insulin-like growth factor binding proteins (IGFBPs), and plasma lipoprotein assembly, remodelling, and clearance. CONCLUSION: The identified plasma protein markers have the potential to serve as biomarkers for differentiating between EC and Hy, as well as for early diagnosis and monitoring of cancer progression.

Patterns of mutations in nine cancer-related genes and PAF development among smoking male patients diagnosed with bladder cancer.

BACKGROUND: Smoking is one of the most popular risk factors provoking bladder cancer (BC). This research intended to estimate cigarette smoking effect involving PAF signs between smoking patients with BC and non-smoking patients with same diagnosis to define relations with pathological characteristics and their prognosis on zero-relapse and disease-associated recovery. METHODS: Two groups of smokers (n = 54) and non-smokers (n = 62) were selected. Both cohorts of patients had BC. They were evaluated utilizing NGS on 9 cancer-related genes and confirmed through the Sanger DNA sequencing and histopathological tests based on H&E staining. The factor of smoking and impact of PAF development by ELISA assay and PAF-R manifestation in terms of immunochemical evaluation on BC areas comparing to a control group (n = 30) was examined involving healthy contributors, including the use of well-designed statistical trials. RESULTS: The multivariate evaluation showed considerable rise in mutation patterns related to smoking among BC patients (group 3), increase in PAF development (***P<0.001) and vivid signs of PAF-R contrasted to non-smokers with BC (group 2) and control group (group 1). All the identified biological changes (gains/losses) were recorded at the same locations in both groups. Patients from group 3 held 3-4 various mutations, while patients from group 2 held 1-3 various mutations. Mutations were not identified in 30 respondents from control group. The most repeated mutations were identified in 3 of 9 examined genes, namely TP53, PIK3CA and PTEN, with highest rates of increase in Group 3. Moreover, histopathological tests revealed barely identifiable and abnormal traits in BC tissues, i.e. were without essential histopathological changes between groups 2 and 3. CONCLUSION: Smoking of cigarettes provokes PAF development due to urothelial inflammation and rise of mutations in 9 cancer-related genes. These are indicative factors of inducing BC.

Morphological and mitochondrial approaches of Hatschekia sargi (Copepoda: Hatschekiidae) as a parasite of Epinephelus chlorostigma.

Little information is available until now about the copepods infecting different fish species. Therefore, this study aimed to provide light on siphonostomatoids infecting Epinephelus chlorostigma. Twenty fish specimens were taken from the Red Sea coast (Jeddah, Saudi Arabia), and ectoparasitic copepods were investigated. Light microscopy and molecular tools were used to examine copepods isolated from fish. Parasitological indexes were calculated and showed that 60% of the examined fish were infected with a mean intensity of 12 parasite/fish. Morphological examination revealed that this copepod species is characterized by all unique features of the genus Hatschekia with special reference to Hatschekia sargi. The taxonomic position of the recovered species in the Hatschekiidae family within Siphonostomatoida was confirmed using phylogenetic analysis based on partial mitochondrial cytochrome c oxidase subunit I (mt COI) gene sequences. The mt COI gene query revealed that the recovered Hatschekia species is closely related to Hatschekia maculatus (gb| JQ664005.1). This study discovers a new host for Hatschekia species isolated from Saudi Arabia and conducts the first genomic investigation of the mt COI gene.

Three cases of colon cancer in four generations of the Saudi family, caused by endogamous germline mutations.

Various research pieces of evidence have been published in recent years, establishing the increasing prevalence of early colon cancer among young people. In this background, the current study aimed to analyze the reasons behind colon cancer recurrence among endogamous consanguineous cases in four generations of a single Saud family. For this study, the authors conducted the whole-exome sequencing analysis to screen for germline mutations in DNA samples from consanguineous cases within the family. After collecting the colon samples, it was analyzed histologically and immunohistochemically with the help of Breast Cancer antibodies (BRCA2 and 1 correspondingly) and H&M staining (hematoxylin and eosin). For this study, 26 at-risk consanguineous cases were considered. Three cases were diagnosed with malignant colon cancer, two with breast cancer, and 17 with germline mutations, yet remain unaffected by cancerous tumors. The rest, four consanguineous cases, are healthy and non-carriers of the mutations. However, as per the exome analysis outcomes, 15 cases inherited germline mutations in nine genes. Nine substitution mutations were present in six of the nine inherited genes in these inherited germline mutations. Furthermore, it also presented six insertion and deletion frameshift mutations in five of nine inherited genes. The immunohistochemical staining process achieved positive staining outcomes for BRCA1 and 2. Therefore, germline mutations inherited from the nine genes of endogamous consanguineous cases of mutation carriers remain the primary reason behind colon cancer recurrence in the same family.

Morphological, Molecular, and Pathological Appraisal of Hymenolepis nana (Hymenolepididae) Infecting Laboratory Mice (Mus musculus).

Hymenolepis nana, typically a parasite found in conventionally established mouse colonies, has zoonotic potential characterized by autoinfection and direct life cycle. The objective of this study was to determine the rate of parasite infection in laboratory mice. The hymenolepidide cestode infected 40% of the 50 mice sampled. The rate of infection in males (52%) was higher than in females (28%). Morphological studies on the cestode parasite showed that worms had a globular scolex with four suckers, a retractable rostellum with 20-30 hooks, and a short unsegmented neck. In addition, the remaining strobila consisted of immature, mature, and gravid proglottids, irregularly alternating genital pores, lobulated ovaries, postovarian vitelline glands, and uteri with up to 200 eggs in their gravid proglottids. The parasite taxonomy was confirmed by using molecular characterization based on the sequence analysis of the mitochondrial cytochrome c oxidase subunit 1 (mtCOX1) gene. The parasite recovered was up to 80% identical to other species in GenBank. High blast scores and low divergence were noted between the isolated parasite and previously described H. nana (gb| AP017666.1). The phylogenetic analysis using the COX1 sequence places this hymenolepidid species of the order Cyclophyllidea.

Plant extract mediated synthesis of ZnO and CeO2 nanoparticles for spectrofluorometric assay of omeprazole and domperidone in pharmaceuticals.

The current research proposed a highly sensitive and selective spectrofluorometric approach for the assay of gastrointestinal medications omeprazole (OMZ) and domperidone (DOM). Green synthesis of metal oxide nanoparticles such as zinc oxide (ZnONPs) and cerium oxide (CeO2NPs) using Pimpinella anisum and Syzygium aromaticum extract was used as fluorescence emission catalysts for the determination of OMZ and DOM. Due to their unique optical properties, nanoparticles (NPs) form the basis for spectrofluorimetric quantification of the selected drugs. The detection studies were performed under λex/λem 350/450 nm and 284/392 nm for OMZ and DOM in the presence of ZnONPs and CeO2NPs, respectively. Under ideal conditions, fluorescence intensities (FI) were linearly with correlation coefficient (r = 0.999) over concentration ranges of 0.1-100 and 0.01-200 µg mL-1 for OMZ, 0.01-100 and 0.01-300 n g mL-1 for DOM in the presence of ZnONPs and CeO2NPs, respectively. Method validation was carried out to guarantee the accuracy, suitability, and precision of the proposed fluorescence (FL) systems for the determination of OMZ and DOM. Analytical method guidelines and requirements were followed. The designed procedure was used effectively to identify the determined drugs in both their pure and commercial versions.

Plasma Proteomic Signature of Endometrial Cancer in Patients with Diabetes.

The incidence and mortality of endometrial cancer (EC) have increased in recent years. There is mounting evidence that diabetes may play a role in the greater incidence of EC. The molecular mechanisms of the interaction between type 2 diabetes and EC are not yet clearly understood yet. The present study was undertaken to investigate the plasma proteomics of EC patients with diabetes in comparison to those of EC patients without diabetes. Plasma samples were obtained from age-matched patients (EC diabetic and EC nondiabetic). Untargeted proteomic analysis was carried out using a two-dimensional differential gel electrophoresis coupled with matrix-assisted laser desorption/ionization time-of-flight mass spectrometry. Of the 33 proteins identified, which significantly differed in the plasma abundance between groups, 17 were upregulated and 16 were downregulated. The majority of the altered proteins are involved in the acute phase reaction, cholesterol metabolism, scavenging of heme from plasma, and plasma lipoprotein assembly and mobilization. α-2-macroglobulin, Ras association domain-containing protein 3, apolipoprotein A-I, α-1B-glycoprotein, and zinc-α-2-glycoprotein were significantly upregulated. The significantly downregulated proteins included haptoglobin, apolipoprotein A-IV, hemopexin, and α-1-antichymotrypsin. The differential expression of proteins found in patients who had EC and diabetes indicated severe disease and a poor prognosis. The protein interaction analysis showed dysregulation of cholesterol metabolism and heme scavenging pathways in these patients.

Emerging role of exosomal microRNA in liver cancer in the era of precision medicine; potential and challenges.

Exosomal microRNAs (miRNAs) have great potential in the fight against hepatocellular carcinoma (HCC), the fourth most common cause of cancer-related death worldwide. In this study, we explored the various applications of these small molecules while analyzing their complex roles in tumor development, metastasis, and changes in the tumor microenvironment. We also discussed the complex interactions that exist between exosomal miRNAs and other non-coding RNAs such as circular RNAs, and show how these interactions coordinate important biochemical pathways that propel the development of HCC. The possibility of targeting exosomal miRNAs for therapeutic intervention is paramount, even beyond their mechanistic significance. We also highlighted their growing potential as cutting-edge biomarkers that could lead to tailored treatment plans by enabling early identification, precise prognosis, and real-time treatment response monitoring. This thorough analysis revealed an intricate network of exosomal miRNAs lead to HCC progression. Finally, strategies for purification and isolation of exosomes and advanced biosensing techniques for detection of exosomal miRNAs are also discussed. Overall, this comprehensive review sheds light on the complex web of exosomal miRNAs in HCC, offering valuable insights for future advancements in diagnosis, prognosis, and ultimately, improved outcomes for patients battling this deadly disease.

Corrigendum: In silico and in vivo evaluation of the anti-cryptosporidial activity of eugenol.

[This corrects the article DOI: 10.3389/fvets.2024.1374116.].

In silico and in vivo evaluation of the anti-cryptosporidial activity of eugenol.

Background: Cryptosporidiosis is an opportunistic parasitic disease widely distributed worldwide. Although Cryptosporidium sp. causes asymptomatic infection in healthy people, it may lead to severe illness in immunocompromised individuals. Limited effective therapeutic alternatives are available against cryptosporidiosis in this category of patients. So, there is an urgent need for therapeutic alternatives for cryptosporidiosis. Recently, the potential uses of Eugenol (EUG) have been considered a promising novel treatment for bacterial and parasitic infections. Consequently, it is suggested to investigate the effect of EUG as an option for the treatment of cryptosporidiosis. Materials and methods: The in silico bioinformatics analysis was used to predict and determine the binding affinities and intermolecular interactions of EUG and Nitazoxanide (NTZ) toward several Cryptosporidium parvum (C. parvum) lowa II target proteins. For animal study, five groups of immunosuppressed Swiss albino mice (10 mice each) were used. Group I was left uninfected (control), and four groups were infected with 1,000 oocysts of Cryptosporidium sp. The first infected group was left untreated. The remaining three infected groups received NTZ, EUG, and EUG + NTZ, respectively, on the 6th day post-infection (dpi). All mice were sacrificed 30 dpi. The efficacy of the used formulas was assessed by counting the number of C. parvum oocysts excreted in stool of infected mice, histopathological examination of the ileum and liver tissues and determination of the expression of iNOS in the ileum of mice in different animal groups. Results: treatment with EUG resulted in a significant reduction in the number of oocysts secreted in stool when compared to infected untreated mice. In addition, oocyst excretion was significantly reduced in mice received a combination therapy of EUG and NTZ when compared with those received NTZ alone. EUG succeeded in reverting the histopathological alterations induced by Cryptosporidium infection either alone or in combination with NTZ. Moreover, mice received EUG showed marked reduction of the expression of iNOS in ileal tissues. Conclusion: Based on the results, the present study signified a basis for utilizing EUG as an affordable, safe, and alternative therapy combined with NTZ in the management of cryptosporidiosis.

SARS-CoV-2 impact on ACE2 expression in NSCLC: mRNA and protein insights COVID-19 associated (ACE2) expression in non-small cell lung cancer (NSCLC).

Non-small cell lung cancer (NSCLC) is a pervasive and challenging global health concern. This research delves into the intricate relationship between NSCLC and ACE2 expression, exploring the potential impact of COVID-19 history on this interaction. Tissue samples were meticulously gathered from a cohort of 32 NSCLC patients, 18 of whom had a documented history of COVID-19 infection. The methodology included extensive investigations, such as cell dissociation, histopathological analysis, immunohistochemistry, cell culture, adhesion assays, immunocytochemistry, RNA isolation, and RT-PCR analysis. The results of this comprehensive study unearthed intriguing findings regarding ACE2 expression patterns within NSCLC tissues. Notably, variations were observed in ACE2 profiles between individuals with and without a prior record of COVID-19 infection, hinting at a dynamic interplay. These discoveries carry profound implications for both the understanding of NSCLC progression and the response to COVID-19 in patients with pre-existing NSCLC. The interrelationship between ACE2 expression, NSCLC, and COVID-19, as revealed in this study, may significantly influence patient outcomes and, potentially, therapeutic strategies. In summary, this research serves as an essential contribution to the growing body of knowledge on NSCLC, offering unique insights into the intricate connections between ACE2, COVID-19, and NSCLC. This information may open new avenues for tailored treatment approaches and clinical management strategies, ultimately benefiting patients grappling with NSCLC in the background of the current COVID-19 pandemic.

Metabolomic Profiling of Blood Plasma in Females with Hyperplasia and Endometrial Cancer.

Uterine cancer is the most prevalent gynecologic malignancy in women worldwide. Endometrial cancer (EC) has an 81% five-year survival rate, depending on disease stage and time of diagnosis. While endometrial cancer is largely treatable when detected early, no established screening techniques are available in clinical practice. As a result, one of the most significant issues in the medical field is the development of novel ways for early cancer identification, which could boost treatment success rates. Liquid chromatography-high-resolution mass spectrometry (LC-HRMS)-based metabolomics was employed to explore the metabolomic markers and pathways unique to this cancer type and link them to the benign endometrial hyperplasia that may progress to cancer in 5% to 25% of patients. The study involved 59 postmenopausal participants, 20 with EC type 1, 20 with benign hyperplasia, and 19 healthy participants. Metabolite distribution changes were analyzed, and 338 of these features were dysregulated and significant. The first two main components, PC1 and PC2, were responsible for 11.5% and 12.2% of the total metabolites, respectively. Compared with the control group (CO), EC samples had 203 differentially expressed metabolites (180 upregulated and 23 downregulated); in hyperplasia (HP), 157 metabolites were dysregulated (127 upregulated and 30 downregulated) compared to the CO group while 21 metabolites exhibited differential regulation (16 upregulated and 5 downregulated) in EC plasma samples compared to the HP group. Hyperplasia samples exhibited similar metabolic changes to those reported in cancer, except for alterations in triglyceride levels, 7a,12 b-dihydroxy-5b-Cholan-24-oic acid, and Hept-2-enedioyl carnitine levels. The metabolites N-heptanoyl glycine and -(Methylthio)-2,3-isopentyl phosphate and formimino glutamic acid can be specific markers for hyperplasia conditions and dimethyl phosphatidyl ethanolamine and 8-isoprostaglandin E2 can be specific markers for EC conditions. Metabolic activities rely on mitochondrial oxidative phosphorylation for energy generation. The changes in metabolites identified in our study indicate that endometrial cancer cells adopt alternative strategies to increase energy production to meet the energy demand, thereby supporting proliferation.

Identification, forensic evidences and effect of the most used lip cosmetics on the human STR profiling at Kingdom of Saudi Arabia.

This study aimed to identify the DNA STR profiles that were obtained from the lips with various lip cosmetics involved in lip pencil, lipsticks and lip gloss for a brand - Makeup Forever and lip balms (Labello brand) - have been popularly used by Saudi women at KSA. The study was involved 35 unrelated participants (healthy female donors) aged between 26 and 32. The swabbing of lip cosmetics was done prior to using them as negative control samples, other sterilized swabs were collected from the used lip cosmetics which contained the lip cells for each participant as a study sample. Moreover, the buccal swabs were firmly collected from the cleaned oral cavities for the same donors as reference samples. The air-drying of the collected swabs was done for ten minutes at room temperature and then stored them at - 20 °C before the DNA analysis. The 7500 Real-Time PCR (qRT-PCR) was quantified the extracted DNA. The amplification of 16 STR loci was done using the AmpFlSTR® Identifiler® PCR amplification kit using the Thermocycler ABI 9700 to amplify the extracted DNA. The Applied Bio-systems 3130™ Genetic Analyzer with Gene Mapper® ID-X Software v3.5 was used to analyze the PCR products. The data for quantifying DNA recorded significant decrease in the concentrations of DNA samples ranged from 0.15 to 0.55 ng/µL in comparison to the reference samples, while DNA was not detected in all the negative control samples. Some STR loci showed considerably high inhibition and low heterozygosity loss in the study samples compared to the reference and negative samples. The possibility of extracting DNA samples from lip cosmetics were used in the present study could be useful and successful in some cases due to the effect of the chemical compositions such as heavy pigments, organic components, and aromatic wax on the STR profiles in the lip cosmetics, especially in the lipsticks, lip glosses and lip pencils.

The function of long non-coding RNA SNHG11 and its working mechanism in triple-negative breast cancer.

Triple-negative breast cancer (TNBC) seriously affects woman's health. The present work is to study the working mechanism of lncRNA SNHG11 in TNBC. The expressions of SNHG11, microRNA (miR)- 7-5p, specificity protein 2 (SP2) and mucin 1 (MUC-1) in TNBC tissues and cells were detected. SNHG11, miR-7-5p and SP2 expressions were then evaluated for TNBC cell malignant behaviors. The relationships among SNHG11, miR-7-5p and SP2 were predicted and verified. Finally, the binding of the transcription factor SP2 to MUC-1 promoter was detected. Abnormally elevated SNHG11, SP2 and MUC-1 expressions were observed in cultured TNBC cells and tumor tissues. SNHG11 knockdown in TNBC cells. Silencing SP2 weakened the promoting effect of SNHG11 on TNBC progression. SNHG11 negatively regulated miR-7-5p expression and positively regulated SP2 expression. SP2 bound to the P2 site of MUC-1 promoter, and SP2 knockdown suppressed MUC-1 expression. It was demonstrated that lncRNA SNHG11 promoted TNBC cell malignant behaviors to facilitate TNBC progression. The study is first of its kinds to unravel the potential of lncRNA SNHG11 in relation to TNBC.

Detecting STR profiles from degrading menstrual blood samples and their use as possible evidence in forensic investigations.

This research explores DNA consistency and attempts to detect STR profiles from the degrading menstrual blood samples (MBS) as reliable forensic evidence. Peripheral (PBS) and MBS of 30 healthy fertile females were taken on the menstrual cycle's second day. They were obtained at different time periods (0, 2, 4, 6, 8, 10, 12, 14, 16, 18, 20, 24, and 48 h) at 25 °C. DNA evaluation was fulfilled to analyze DNA profiles. A considerable elevation in the median concentrations of DNA between 0 and 14-h intervals were documented, whereas decreased extents were registered between 16 and 48 h. Moreover, complete STR profiles (24/24) for DNA were discovered in all the intervals (0, 2, and 48 h). Periods of 0-8 h demonstrated the maximum extents of DNA materials. Full STR were discovered in all the intervals (0, 2, and 48 h). Eventually, MBS can be utilized as forensic evidence.

FGFR3 and FGFR4 overexpression in juvenile nasopharyngeal angiofibroma: impact of smoking history and implications for personalized management.

Lifestyle factors, including smoking, have been linked to neoplastic diseases, and reports suggest an association between smoking and overexpression of FGFR (fibroblast growth factor receptor) in certain neoplasms. This study aims to assess the expression of FGFR3 and FGFR4 genes in patients with and without a history of smoking.A total of 118 participants were recruited, including 83 Juvenile Nasopharyngeal Angiofibroma (JNA) patients and 35 healthy participants, the JNA patients were further stratified as smokers and nonsmokers. Total RNA was extracted from the blood & saliva sample by using TRIzol reagent, and quantified using a Nanodrop, and then subjected to gene expression analysis of FGFR3/4 using RT-PCR. Immunohistochemistry analysis was employed using fresh biopsies of JNA to validate the findings. All experiments were performed in triplicates and analysed using the Chi-Square test (P < 0.05). Smokers exhibited significantly lower total RNA concentrations across all sample types (P < 0.001). The study revealed significant upregulation of both FGFR3/4 genes in JNA patients (P < 0.05). Moreover, FGFR3 expression was significantly higher among smokers 66% (95% CI: 53-79%) compared to non-smokers 22% (95% CI: 18-26%). Immunohistochemistry analysis demonstrated moderate to strong staining intensity for FGFR3 among smokers. The study highlights the overexpression of FGFR3/4 genes in JNA patients, with a stronger association observed among smokers. Furthermore, medical reports indicated higher rates of recurrence and bleeding intensity among smokers. These findings emphasize the potential role of FGFR3 as a key molecular factor in JNA, particularly in the context of smoking.

Ultrasensitive Functionalized Polymeric-Nanometal Oxide Sensors for Potentiometric Determination of Ranitidine Hydrochloride.

Two metal oxide nanoparticles, magnesium oxide nanoparticles (MgONPs) and aluminum oxide nanoparticles (Al2O3NPs), were synthesized from green sources, Salvia officials and Cuminum cyminum seed extract, respectively. These nanoparticles were used for construction of potentiometric enhancement sensors employed for the estimation of ranitidine hydrochloride (RNT) in authentic powder and commercial products. The electroactive substance ranitidine-phosphotungstate (RNT-PT) was formed by combining RNT with phosphotungstic acid (PTA) in the presence of plasticizing material o-nitrophenyloctyl ether (o-NPOE). The outcomes showed that the enhanced MgO and Al2O3 nanosensors behaved linearly across the concentration ranges 1.0 × 10-9-1.0 × 10-2 and 1.0 × 10-10-1.0 × 10-2 mol L-1, respectively. However, the conventional sensor (RNT-PT) displayed a linearity over 1.0 × 10-6-1.0 × 10-2 mol L-1. Least square equations were calculated as EmV = (54.1 ± 0.5) log (RNT) + 762.33, EmV = (58.6 ± 0.2) log (RNT) + 696.48, and EmV = (52.2 ± 0.7) log (RNT) + 756.76 for enriched nanometal oxides modified and conventional sensors, respectively. The correlation coefficients of regression equations were 0.9997, 0.9995, and 0.9992 for the above suggested sensors, respectively. The recorded results showed excellent sensitivity and selectivity of the modified nanometal oxide sensors for the quantification of the analyzed drug in its authentic samples and commercial products.

Pancreatic Pathological Changes in Murine Toxoplasmosis and Possible Association with Diabetes Mellitus.

BACKGROUND: Previous studies have reported involvement of Toxoplasma gondii (T. gondii) infections in the pathogenesis of some autoimmune diseases, such as polymyositis, rheumatoid arthritis, autoimmune thyroiditis, and Crohn's disease. However, data on the association between T. gondii infections and Type 1 diabetes mellitus (T1DM) are still controversial. Therefore, in the present study, we aimed to investigate the pancreatic pathological changes in mouse models with acute and chronic toxoplasmosis and their association with T1DM. MATERIALS AND METHODS: Three groups (10 mice each) of male Swiss Albino mice were used. One group of mice was left uninfected, whereas the second and third groups were infected with the acute virulent T. gondii RH strain and the chronic less virulent Me49 T. gondii strain, respectively. T. gondii-induced pancreatic pathological changes were evaluated by histopathological examination of pancreatic tissues. Moreover, the expression of insulin, levels of caspase-3, and the pancreatic infiltration of CD8+ T cells were evaluated using immunohistochemical staining. RESULTS: Pancreatic tissues of T. gondii-infected animals showed significant pathological alterations and variable degrees of insulitis. Mice with acute toxoplasmosis exhibited marked enlargement and reduced numbers of islets of Langerhans. However, mice with chronic toxoplasmosis showed considerable reduction in size and number of islets of Langerhans. Moreover, insulin staining revealed significant reduction in ß cell numbers, whereas caspase-3 staining showed induced apoptosis in islets of Langerhans of acute toxoplasmosis and chronic toxoplasmosis mice compared to uninfected mice. We detected infiltration of CD8+ T cells only in islets of Langerhans of mice with chronic toxoplasmosis. CONCLUSIONS: Acute and chronic toxoplasmosis mice displayed marked pancreatic pathological changes with reduced numbers of islets of Langerhans and insulin-producing-ß cells. Since damage of ß cells of islets of Langerhans is associated with the development of T1DM, our findings may support a link between T. gondii infections and the development of T1DM.