Anti-inflammatory effects of extracellular vesicles and cell-free supernatant derived from Lactobacillus crispatus strain RIGLD-1 on Helicobacter pylori-induced inflammatory response in gastric epithelial cells in vitro.

Helicobacter pylori infection is the major risk factor associated with the development of gastric cancer. Currently, administration of standard antibiotic therapy combined with probiotics and postbiotics has gained significant attention in the management of H. pylori infection. In this work, the immunomodulatory effects of Lactobacillus crispatus-derived extracellular vesicles (EVs) and cell-free supernatant (CFS) were investigated on H. pylori-induced inflammatory response in human gastric adenocarcinoma (AGS) cells. L. crispatus-derived EVs were isolated by ultracentrifugation and physically characterized by dynamic light scattering (DLS), transmission electron microscopy (TEM), and scanning electron microscopy (SEM). Furthermore, the protein content of L. crispatus-derived EVs was also evaluated by SDS-PAGE. Cell viability of AGS cells exposed to varying concentrations of EVs and CFS was assessed by MTT assay. The mRNA expression of IL-1ß, IL-6, IL-8, TNF-α, IL-10, and TGF-ß genes was determined by RT-qPCR. ELISA was used for the measurement of IL-8 production in AGS cells. In addition, EVs (50 µg/mL) and CFS modulated the H. pylori-induced inflammation by downregulating the mRNA expression of IL-1ß, IL-6, IL-8, and TNF-α, and upregulating the expression of IL-10, and TGF-ß genes in AGS cells. Furthermore, H. pylori-induced IL-8 production was dramatically decreased after treatment with L. crispatus-derived EVs and CFS. In conclusion, our observation suggests for the first time that EVs released by L. crispatus strain RIGLD-1 and its CFS could be recommended as potential therapeutic agents against H. pylori-triggered inflammation.

Sclerosing angiomatoid nodular transformation of the spleen in a child with anemia: a case report and review of the literature.

BACKGROUND: Sclerosing angiomatoid nodular transformation of the spleen is a relatively rare benign vascular lesion in both adult and pediatric age groups with unclear etiopathogenesis and variable clinical presentations. Many benign and also malignant splenic masses could mimic sclerosing angiomatoid nodular transformation, both clinically and radiologically. Herein, we report our experience with a case of sclerosing angiomatoid nodular transformation in a 3-year-old girl. CASE REPORT: A 3-year-old Iranian girl presented with abdominal pain, back pain, and constipation for 2 weeks. She was being followed up by a pediatrician due to her short stature and persistent anemia. Physical examination showed stable vital signs, short stature, pallor, and a puffy face. Laboratory evaluation showed normochromic normocytic anemia with a normal reticulocyte count, ferritin, and hemoglobin electrophoresis. Radiologic assessments revealed a hypoechoic lesion in the spleen with high vascularity, clinically suspected to be lymphoma. She was operated on, and after partial splenectomy, pathologic evaluation of the spleen showed a solitary, well-demarcated, and unencapsulated dark mass. Microscopic examination revealed micronodular appearance composed of irregular-shaped vascular spaces lined by plump endothelial cells and surrounded by concentric collagen fibers, features in keeping with sclerosing angiomatoid nodular transformation. The patient's anemia was resolved after surgery, and no clinical or radiologic deficits were noted during the 10-month follow-up visits. CONCLUSION: Although sclerosing angiomatoid nodular transformation is exceedingly rare in children, it should be considered a differential diagnosis in pediatric splenic neoplasms with concurrent hematologic manifestations, such as anemia.

Immunomodulatory effects of live and pasteurized Lactobacillus crispatus strain RIGLD-1 on Helicobacter pylori-triggered inflammation in gastric epithelial cells in vitro.

BACKGROUND: Helicobacter pylori infection is considered as the major risk factor for gastric adenocarcinoma. Today, the increasing emergence of antibiotic-resistant strains has drastically decreased the eradication rate of H. pylori infection. This study was aimed to investigate the inhibitory and modulatory effects of live and pasteurized Lactobacillus crispatus strain RIGLD-1 on H. pylori adhesion, invasion, and inflammatory response in AGS cell line. METHODS AND RESULTS: The probiotic potential and properties of L. crispatus were evaluated using several functional and safety tests. Cell viability of AGS cells exposed to varying concentrations of live and pasteurized L. crispatus was assessed by MTT assay. The adhesion and invasion abilities of H. pylori exposed to either live or pasteurized L. crispatus were examined by gentamycin protection assay. The mRNA expression of IL-1ß, IL-6, IL-8, TNF-α, IL-10, and TGF-ß genes was determined by RT-qPCR from coinfected AGS cells. ELISA was used for the detection of IL-8 secretion from treated cells. Both live and pasteurized L. crispatus significantly decreased H. pylori adhesion/invasion to AGS cells. In addition, both live and pasteurized L. crispatus modulated H. pylori-induced inflammation by downregulating the mRNA expression of IL-1ß, IL-6, IL-8, and TNF-α and upregulating the expression of IL-10, and TGF-ß cytokines in AGS cells. Furthermore, H. pylori-induced IL-8 production was dramatically decreased after treatment with live and pasteurized L. crispatus. CONCLUSIONS: In conclusion, our findings demonstrated that live and pasteurized L. crispatus strain RIGLD-1 are safe, and could be suggested as a potential probiotic candidate against H. pylori colonization and inflammation.

Uninvited guest, Balantidium coli in urine in a patient with bladder cancer: A case report and review of the literature.

Key Clinical Message: In contrast to intestinal balantidiasis, which is widespread throughout the world, urinary balantidiasis is uncommon. It often affects people with underlying diseases, and acute infections may be fatal. Even though urine is not typical for this parasite, specific morphologic characteristics can aid in accurate diagnosis. Abstract: Balantidium coli is a ciliated protozoan which can infect intestinal system. Urinary balantidiasis is an extremely rare infection that may cause serious issues in patients with underlying diseases. Herein, we present a case of urinary balantidiasis in a patient with bladder cancer.

Splenic Lymphangioma Mimicking Lymphomatous Involvement: A Case Report with Review of the Literature.

Lymphangioma is a benign malformation of lymphatic vessels usually found in the head and neck areas or axilla. They may involve visceral organs with a lower percentage. Splenic lymphangioma is a rare tumor. This disease is often seen in children but may be diagnosed incidentally in adults. Most patients are asymptomatic, but in large and multifocal lesions, the patient may have some nonspecific symptoms such as abdominal pain, abdominal distention, nausea, vomiting, and loss of appetite. Physical examination may show no specific findings or detect palpable masses. The preoperative diagnosis of splenic lymphangioma is challenging. Histopathological evaluation and sometimes immunohistochemistry tests can result in a definitive diagnosis. In this study, we present an 18-year-old man, with Burkitt's lymphoma who underwent laparotomy and total splenectomy as a result of cystic lesions discovered accidentally during imaging with the final diagnosis of splenic lymphangioma after histopathological evaluation.

Bronchobiliary fistulae as a complication of untreated pulmonary hydatid cyst presenting with bilioptysis: A report of two cases.

We reported two patients, a 45-year-old lady and a 48-year-old man, known cases of untreated liver and lung hydatid cysts complicated with bronchobiliary fistulae. Surgery was performed, and bronchobiliary fistulae were diagnosed intraoperatively. Lobectomy was done on the lobe, which was chronically infected. Symptoms resolved after surgery in both cases. Green-colored sputum in a patient with a history of echinococcosis should raise the physician's attention to the probability of a connection between the bronchial tree and the biliary tract. Surgery in advanced cases is a suitable therapeutic option.

Do Serological Tests Eliminate the Need for Endoscopic Biopsy for the Diagnosis of Symptomatic Patients with Celiac Disease? A Retrospective Study with Review of Literature.

Background: Celiac disease is one of the most common genetic allergies worldwide. The prevalence of celiac disease in Iran is similar to or even higher than the global prevalence. Celiac disease is a chronic inflammatory disease that affects the small intestine. Affected patients are allergic to gluten protein that exists in some grains, such as wheat and barley. Methods: Serological endomysial IgA antibody (EMA-AB) and tissue transglutaminase IgA antibody (TTG-IgA) tests were performed on 114 patients aged the ages of 0-18 years with histopathological findings of celiac disease. The results of these tests were compared to the results of the histopathological study of the duodenal biopsy. Results: Based on the receiver operating characteristic (ROC) curve and a calculation of the TTG-IgA test's sensitivity and specificity, the best diagnostic limit for the TTG-IgA test is 144, which has the best sensitivity and specificity. At this value (cut-off), the test's sensitivity was 62%, and the specificity was 93.7%. For the endomysial test, sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were 80%, 93%, 90%, and 75%, respectively. Conclusion: The diagnostic accuracy of the endomysial test is better than that of the TTG-IgA test in general for diagnosing patients with celiac disease. In the TTG-IgA test, false-positive cases are high due to a cut-off of 20, reducing the test's specificity. In these false-positive cases, the endomysial test helps in better diagnosis.

The oncolytic activity of Clostridium novyi nontoxic spores in breast cancer.

Introduction: Hypoxia context is highly specific for tumors and represents a unique niche which is not found elsewhere in the body. Clostridium novyi is an obligate anaerobic bacterium. It has a potential to treat tumors. The aim of this study was to produce the C. novyi nontoxic spores and to investigate its oncolytic effect on breast cancer in mice model. Methods: Primarily, the lethal toxin gene in C. novyi type B was removed. Colonies were isolated using PCR testing. To assure the removal of alpha-toxin, plasmid extraction and in vivo assay were conducted. Next, to treat breast cancer model in different sizes of tumors, a single dose of spores of C. novyi nontoxic was tested. Results: The results denoted that C. novyi nontoxic lost lethal toxin and a--ppeared to be safe. For smaller than 1000 mm3 tumors, a single dose of C. novyi nontoxic was able to cure 100% of mice bearing breast tumors. Hence the mice remained free of tumor relapse. Tumors larger than 1000 mm3 were not cured by a single dose- of C. novyi nontoxic treatment. Conclusion: The experiment concluded that the C. novyi nontoxic might be a suitable and safe candidate, a novel therapeutic approach to encounter such hypoxic regions in the center of tumors. Research also showed that bacteriolytic therapy by C. novyi nontoxic could lead to regression in small tumor.

Adenocarcinoma Metastasis from Colon to the Thyroid.

Background: Colorectal cancer metastasis to the thyroid is extremely rare and happens in the late course of the disease. Case Description. Here is the report of a 55-year-old female patient who came to us with the chief complaint of cough, diagnosed with colon metastasize to the lung. Surgical resection of the mass was performed. However, a thyroid mass was found incidentally in her postoperative follow-up. Fine needle aspiration of thyroid mass showed papillary thyroid carcinoma. But, after thyroidectomy, the origin of the mass was reported to be adenocarcinoma metastasis from colon cancer. Conclusion: Although thyroid metastasis from colorectal cancer rarely occurs, it should be considered in a patient with a solitary thyroid nodule and a past medical history of colon cancer. Surgical treatment is the preferred choice of treatment in these cases.

Diagnostic Accuracy of Direct Immunofluorescence Test on Paraffin-Embedded Blocks in Comparison with Frozen Section Blocks in Renal Biopsies.

Background: In several published research, the evaluation of renal disorders using immunofluorescence on formalin-fixed, paraffin-embedded (FFPE) tissue sections versus immunofluorescence on frozen sections was compared. Each technique's accuracy varies greatly. This study's objective was to assess IF-P as a potential replacement for IF-F in the diagnosis of renal biopsy specimens. Materials and Methods: To show immunoglobulin IgA, IgG, IgM, and C3 immune deposits, proteinase K digestion of paraffin-embedded renal biopsy was standardized and used in 51 renal biopsies. Sensitivity, specificity, false-positive, and false-negative values were calculated. Results: IF-P showed a sensitivity of 93.1%, 76.9%, 63.6%, and 33.3%, and a specificity of 100%, 97.3%, 95%, and 100% for IgG, IgA, IgM, and C3, respectively. Compared to cases that had both routine IF and IF-P, 50 of 51 showed either the same amount of staining for the diagnostic immunoglobulin/complement or a small amount of difference. In most of the cases (49 of 51), diagnostic findings were found. Conclusion: IF-P is a sensitive and precise approach for assessing immune deposits in renal tissue biopsies. We come to the conclusion that IF-P serves as a beneficial salvage immunohistochemistry method for renal biopsies that do not contain enough cortical tissue for IF-F.

The interplay between Helicobacter pylori and the gut microbiota: An emerging driver influencing the immune system homeostasis and gastric carcinogenesis.

The human gut microbiota are critical for preserving the health status because they are required for digestion and nutrient acquisition, the development of the immune system, and energy metabolism. The gut microbial composition is greatly influenced by the colonization of the recalcitrant pathogen Helicobacter pylori (H. pylori) and the conventional antibiotic regimens that follow. H. pylori is considered to be the main microorganism in gastric carcinogenesis, and it appears to be required for the early stages of the process. However, a non-H. pylori microbiota profile is also suggested, primarily in the later stages of tumorigenesis. On the other hand, specific groups of gut microbes may produce beneficial byproducts such as short-chain fatty acids (acetate, butyrate, and propionate) that can modulate inflammation and tumorigenesis pathways. In this review, we aim to present how H. pylori influences the population of the gut microbiota to modify the host immunity and trigger the development of gastric carcinogenesis. We will also highlight the effect of the gut microbiota on immunotherapeutic approaches such as immune checkpoint blockade in cancer treatment to present a perspective for further development of innovative therapeutic paradigms to prevent the progression of H. pylori-induced stomach cancer.

Future prospects of bacteria-mediated cancer therapies: Affliction or opportunity?

Cancer, as a disease characterized by uncontrolled growth of cells, is recognized as one of the significant challenges in the field of health and medicine. There are various treatments for cancer like surgery, hormone therapy, chemotherapy, etc., but they have negative effects on the patient's lifestyle. Numerous side effects, and recently the emergence of drug resistance to these methods are weaknesses of these treatments. The utilization of bacteria as a treatment for cancer has attracted scientists' attention in the last decade. There are various methods of using bacteria to treat cancer, including the use of live, attenuated, or genetically engineered microbes, the use of bacterial toxins as an immunotoxin or conjugated to tumor antigens, bacteria-based cancer immunotherapy, bacterial vectors for gene-directed enzyme prodrug, and also the undeniable role of probiotics in treatment, are the cases that today are used for treatment. Bacterial therapy has shown a greater promise in cancer treatment due to its ability to lyse the tumor cells and deliver therapeutic products. However, the potential cytotoxicity of bacteria for healthy tissues, their inability to entirely lyse cancerous cells, and the possibility of mutations in their genomes are among the challenges of bacteriotherapy for cancer. Herein, we summarize the mechanism of bacteria, their potential benefits and harms, and the future of research in this field.

Carcinoma of Unknown Primary Origin: Application of Immunohistochemistry With Emphasis to Different Cytokeratin 7 and 20 Staining Patterns.

BACKGROUND: Although the primary origin of some carcinomas may be obscure to clinicians, its identification is crucial as it affects prognosis and treatment (especially novel targeted therapies). Immunohistochemistry (IHC) may be helpful in identifying the primary origin of carcinomas. This retrospective survey aimed to evaluate the frequency and accuracy of each IHC marker used to determine the origin of carcinomas. METHODS: The review of pathology department archives revealed 307 cases of cancer of unknown primary origin (CUP) between 2015 and 2020, which were accessible in the department archives. Demographic information, site of biopsy, clinical and pathologic diagnoses, and IHC results of the patients were collected. RESULTS: The patients included 157 (51.15%) men and 150 (48.85%) women. The age of the patients ranged from 14 to 92 years, including 106 (34.5%) expired cases. In 27% of cases, the primary origin of carcinoma remained unknown. The agreement between pathologic and clinical diagnoses was 59%. The most common pattern of cytokeratin (CK) expression in CUP was CK7+/CK20- (55.3%), followed by CK7-/CK20- (19%), CK7+/CK20+ (15%), and CK7-/CK20+ (10.7%), respectively. CONCLUSION: The IHC analysis may improve the diagnosis of CUPs. However, the origin of some cases remains unknown despite an IHC analysis, thereby necessitating the use of more diagnostic procedures or gene expression studies for reaching a definitive diagnosis.

Mediastinal thymoma in a patient with previous rectal and breast cancers: A report of a case with multiple primary cancers and review of literature.

A 42-year-old female patient with intellectual disability was presented to us as a newly diagnosed case of thymoma. She was identified as a case of multiple primary cancers, including adenocarcinoma of the rectum, carcinoma of the breast, and mediastinal thymoma, in a 15-year period, who underwent chemotherapy, radiotherapy, and surgical resection.

Two cases of cardiac hemangioma in different anatomical locations presenting with chest pain and palpitation.

Cardiac hemangiomas are benign, slow-growing tumors among the most common soft tissue tumors in the human body. Surgical resection is highly recommended for cardiac hemangiomas in symptomatic patients. We report our cases with a review of the literature on cardiac hemangiomas.

Multifocal EBV-associated smooth muscle tumors in a patient with cytomegalovirus infection after liver transplantation: a case report from Shiraz, Iran.

INTRODUCTION: Immunodeficient patients, including the recipients of solid organs, exhibit an increase in the incidence of neoplasms. Post-transplant smooth muscle tumor (PTSMT) is a distinct and infrequent entity of these groups of neoplasms. Epstein-Barr virus (EBV) is considered to be involved in the etiology of this neoplasm. CASE REPORT: A 28-year-old man who underwent liver transplantation presented with abdominal pain and diarrhea for several months. He had a history of resistant systemic cytomegalovirus (CMV) infection after transplantation. Radiologic evaluation and colonoscopy revealed multiple liver, spleen, lung, and colon lesions. Microscopic assessment of colon and liver lesions using IHC study were in favor of spindle cell proliferation with mild atypia and a mild increase in mitotic rate without any necrosis, with features of smooth muscle tumor. Considering the transplantation history, EBER chromogenic in situ hybridization (CISH) study on paraffin blocks was requested, which demonstrated EBV RNA in tumor cell nuclei, suggesting EBV-associated smooth muscle tumor. In addition, PCR for CMV on paraffin blocks was positive. PCR for EBV and CMV viremia were negative. The dosage of immunosuppressive agents was reduced, and currently, he is being followed, with slow expansion in the size of the lesions. CONCLUSION: Although the incidence of post-transplant smooth muscle tumors (PTSMTs) is low, it should be remained in the differential diagnosis in post-transplantation patients, especially dealing with multifocal tumors. As strong stimulant for smooth muscle tumors, close follow-up and screening for EBV and CMV infection and early treatment at the time of diagnosis are recommended to avoid these virus-induced tumors.

Correlation between HDL2, HDL3 and serum ferritin levels with fatty liver and NAFLD activity score (NAS) in liver histology of organ donors.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is one of the most important liver diseases. High-density lipoprotein (HDL) has anti-atherogenic properties and its reduction can be associated with fatty liver. Serum ferritin levels are usually elevated in patients with NAFLD. This study aimed to evaluate the correlation between HDL subtypes and serum ferritin levels with evidence of NAFLD in liver histology of organ donors. METHODS: One hundred organ donor patients who were eligible for the study were included in the study and ferritin; HDL2 and HDL3 were measured in blood samples. Donated liver tissue biopsy specimens were evaluated for fatty liver and NAFLD activity score (NAS). In addition, AST and ALT were measured in recipients 24 h after transplant. All data abstracted and analyzed statistically. RESULTS: Serum HDL2 levels and HDL2/HDL3 ratio in patients with NAS > 1 were significantly lower (P < 0.05). Serum levels of HDL3 and ferritin were not significantly associated with NAS >1 (P > 0.05). In addition, serum ferritin > 1000 ng/ml in organ donors associated with increased AST and ALT levels 24 h after transplantation in the liver organ recipient. CONCLUSIONS: Lower HDL2 values and HDL2/HDL3 ratio were associated with increased NAFLD activity score, but HDL3 and ferritin did not show such a relationship. In addition, higher levels of ferritin in organ donors may be associated with increased AST and ALT 24 h after liver transplantation in the organ recipient.

Isolation and identification of the bacterium producing antitumor and antimicrobial compounds derived from Iranian swamp frog (Rana ridibunda) skin.

BACKGROUND AND OBJECTIVES: Cancer incidence and recurrence, antibiotic resistance, and overuse of antibiotics have become a global concern. The purpose of this study was to identify and isolate bacteria from the skin of the Rana ridibunda, Iranian swamp frog, which has produced antimicrobial compounds, and investigate its cytotoxic activity on the breast (MCF7) and glioblastoma (U87) cancer cell line. MATERIALS AND METHODS: An antibiotic-producing bacterium was isolated from the frog skin. The bacterium was identified based on 16S rDNA sequencing and biochemical and morphological characteristics. Antimicrobial activity of the culture supernatant was examined by disc diffusion and MIC methods. Cytoplasmic and cell wall extracts of bacteria were prepared by sonication. SDS-PAGE was then used to examine protein contents of them. The cancer cell lines were treated with cytoplasmic and cell wall extracts at different concentrations. The effects of cytotoxicity were assessed by MTT assay at 24 and 48 h intervals. Finally, the results were analyzed by SPSS. RESULTS: The isolated bacterium was identified as a new strain of Bacillus atrophaeus. MIC and disc diffusion methods showed that the Bacillus atrophaeus antimicrobial activity was broad spectrum. MTT assay showed IC50 values 30 µg/ml and 20 µg/ml for U87 and MCF7 cells after 24-48 h exposure, respectively. CONCLUSION: The cytoplasmic extracts of Bacillus atrophaeus has anticancer potential and can be used as an alternative or complementary candidate in the treatment of cancer. Further in vivo and in vitro mechanistic studies are suggested to confirm the biological activities.

Adrenocortical adenoma with myelolipomatous metaplasia: a potential diagnostic pitfall: a case report and review of the literature.

BACKGROUND: Adrenal incidentalomas are often found during investigation for another tumor or unrelated problems. Except for adrenal myelolipoma (second most common primary adrenal incidentaloma following adrenocortical adenomas), adrenal lipomatous tumors are uncommon generally and are often described as case reports in the literature. Since the amount of fat is variable, without the help of advanced imaging techniques, some adrenal lipomatous tumors may be misdiagnosed before pathologic examination. Herein, we report a case of adrenal adenoma with myelolipomatous metaplasia that was excised as a periceliac mass in the setting of recurrent pancreatic cyst. CASE REPORT: A 45-year-old Iranian woman with hypertension and end-stage renal disease presented with recurrence of a pancreatic cyst (previous pathologic report was mucinous cyst adenoma). During exploratory laparotomy, the mentioned pancreatic cyst was tightly attached to the stomach and jejunum. There was also a periceliac round rubbery lesion (firstly diagnosed by endoscopic ultrasound) that was excised for ruling out malignancy. Histologic examination of the periceliac mass was found to be adrenocortical adenoma with foci of myelolipomatous metaplasia. The pancreatic cyst histology was just a pseudocyst. CONCLUSION: Our case highlights the significance of complete evaluation of incidental findings before surgical intervention, even in the setting of another primary tumor. Myelolipoma and myelolipomatous change (metaplasia) are two different entities. Although very similar as to pathogenesis, there are still some differences.

Concomitant BK virus infection and visceral Leishmaniasis in a pediatric liver transplant recipient.

BACKGROUND: Solid organ transplant recipients are vulnerable to various unusual infections. Visceral Leishmaniasis (VL) is a protozoal opportunistic infection, which may affect the immune-suppressed hosts and solid organ transplant recipients. The BK virus infection is an evolving challenge in kidney transplant recipients. However, there are very few reports of BK virus (BKV) nephropathy involving the native kidney in liver transplant recipients. To the best of our knowledge, this is the first report of the simultaneous occurrence of these rare infections in a liver transplant recipient. CASE REPORT: The patient was a 9-year-old girl, a case of liver transplantation who presented with the incidental finding of proteinuria, azotemia, and cytopenia. Investigations revealed that she had concomitant BKV nephropathy and visceral leishmaniasis. Both infections were successfully treated. CONCLUSION: BK virus should be considered as a cause of nephropathy in liver transplant recipients. The presenting features of fever, cytopenia, and splenomegaly in a post-transplant patient should remind of unusual infections such as VL other than the common post-transplant conditions.