Human protozoa infection and dysplasia in ulcerative colitis: a neglected aspect in a prominent disease.

The chance of getting colorectal cancer (CRC) is higher in people with chronic ulcerative colitis (UC). The impact of parasitic infections on UC is underappreciated. The purpose of this study was to look into the effect of intestinal protozoal infections on the dysplastic changes generated by UC. The research included 152 adult patients with histologically confirmed UC and 152 healthy controls. Fecal samples were examined for the presence of parasites and fecal calprotectin (FC). The enzyme-linked immunosorbent assay measured serum anti-p53 antibodies (p53Abs) and metallothioneins (MTs). The advanced oxidation protein products (AOPPs) and reduced glutathione (GSH) levels were measured by a spectrophotometric method in all subjects. Serum C-reactive protein (CRP) and IL-6 were also measured. In addition, histopathological and immunohistochemical investigations of intestinal tissue were done. Our results exhibited significant increases in FC and CRP, IL-6, AOPPs, MTs, and p53Abs in ulcerative colitis patients with parasitic infections compared to those without parasites. In contrast, GSH levels showed a significant decrease in the same group compared with other groups. Histopathological and immunohistochemical assessments of intestinal tissue signified severe inflammation and strong expression of PD-L1 in patients with parasitic infections compared to others without parasitic infections. Our research indicated a greater frequency of intestinal protozoa in UC patients with elevated inflammatory and dysplastic biomarker levels. This suggests that these parasites may be involved in the etiology of chronic UC and the associated carcinogenetic process. This is the first report of a link between parasitic infections and dysplastic alterations in UC patients.

Mitigation of Toxoplasma gondii-induced ileitis by Trichinellaspiralis infection pinpointing immunomodulation.

The current study sought to investigate the potential role of Trichinellaspiralis infection in the treatment of T. gondii-induced ileitis. Forty male Swiss albino mice were divided into four groups:a normal control group Igiven only phosphate-buffered saline (PBS), Group II givenPBS for 28 days then infected with T. gondii cysts for the induction of gastroenteritis, Group III infected only with T. spiralis larvae, and Group IV concurrently infected with T. spiralis larvae, then 28 days post infection, enteritis was induced by oral inoculation withT. gondii cysts. Histopathologicaland immunohistochemicalassessmentswere performed to determine the levels of inflammatory markers nuclear factor- κB (NF-κB) and myeloperoxidase in the ileum samples.Theconcentrations of cytokinesIFN-γ and IL10 were measured in successive serum samples. Histological assessment revealed severe inflammatory infiltrations in ileum samples of T. gondiimonoinfected mice. In addition, the immunological assessment revealed elevated levels of IFN-γ and decreased IL10 concentrations in blood samples. Clear improvement of inflammations, besidesthe decreasedlevels of IFN-γ and increased IL10 concentrations in blood samples were detected in T. spiraliscoinfected animals.Theileal tissue revealed elevated expression of (NF-κB) and myeloperoxidase signaling, all of which were mitigated by T. spiralis coinfection. There is a possibility that regulatory T cells are immunomodulated, releasing anti-inflammatory cytokines while suppressing pro-inflammatory cytokines, causing its therapeutic impact. Trichinellaspiralis infection has the potential to be used for treatment of T. gondii-induced ileitis. As a consequence of these encouraging results, T. spiralis crude and secretory-excretory antigens coated on nanoparticles are being studied in our future research.

Novel adenosine derivatives against SARS-CoV-2 RNA-dependent RNA polymerase: an in silico perspective.

BACKGROUND: SARS-CoV-2 is a newly emerged human coronavirus that severely affected human health and the economy. The viral RNA-dependent RNA polymerase (RdRp) is a crucial protein target to stop virus replication. The adenosine derivative, remdesivir, was authorized for emergency use 10 months ago by the United States FDA against COVID-19 despite its doubtful efficacy against SARS-CoV-2. METHODS: A dozen modifications based on remdesivir are tested against SARS-CoV-2 RdRp using combined molecular docking and dynamics simulation in this work. RESULTS: The results reveal a better binding affinity of 11 modifications compared to remdesivir. Compounds 8, 9, 10, and 11 show the best binding affinities against SARS-CoV-2 RdRp conformations gathered during 100 ns of the Molecular Dynamics Simulation (MDS) run (- 8.13 ± 0.45 kcal/mol, - 8.09 ± 0.67 kcal/mol, - 8.09 ± 0.64 kcal/mol, and - 8.07 ± 0.73 kcal/mol, respectively). CONCLUSIONS: The present study suggests these four compounds as potential SARS-CoV-2 RdRp inhibitors, which need to be validated experimentally.

The delayed death-causing nature of Rosmarinus officinalis leaf extracts and their mixture within experimental chronic toxoplasmosis: Therapeutic and prophylactic implications.

BACKGROUND: The restricted effect, significant toxicity, and emerging resistance of anti-toxoplasmosis synthetic agents impose the search for alternatives. The current research aimed to evaluate the prophylactic and therapeutic efficacy of Rosmarinus officinalis extracts and their mixtures against chronic murine toxoplasmosis and to clarify the phenomenon of delayed death. METHODS: This research included two experimental designs, the first to test the preventive and curative efficacy of the extracts and the second to assess delayed death in mice infected with the ME49 strain of Toxoplasma gondii. The essential oils of the plant were analyzed by gas chromatography/mass spectrometry. RESULTS: Treatment with a mixture of rosemary extracts displayed reduction rates of 81% for T. gondii cyst burden and 23% for cyst viability. The reinfected group with the pretreated cysts reported 93.4% reduction in cyst burden and 95.4% in cyst viability. Moreover, 90% reduction of the infectivity rate was obtained. The therapeutic efficacy of this mixture was superior to its valuable prophylactic effect. Histopathological examination of liver and brain tissue exhibited marked improvement. Both extracts possess free radical scavenging and antioxidant activities evidenced by high expression of iNOS stain. Our results were signified by low BAG-1 gene expression and massive mutilation of T. gondii cyst in the targeted group using scanning electron microscopy. Analysis of R. officinalis revealed the presence of isobornylformate as a novel ingredient. CONCLUSIONS: R. officinalis displays a therapeutic rather than prophylactic potential, indicating the emergence of an effective safe alternative therapy.

Multiple endocrine neoplasia type 1 (MEN1) presenting with renal stones: Case report and review.

Multiple endocrine neoplasia type 1 (MEN1) is a complex, autosomal dominant inherited syndrome characterized by 3 different tumors (parathyroid, anterior pituitary, and pancreatic islet). The diagnosis is defined clinically by the presence of 2 or more primary tumors. We report the case of a 35 years old patient who presented with recurrent renal stones and imaging findings for MEN1. Computed tomography pancreas revealed a mass in the tail which was confirmed by magnetic resonance imaging. Ultrasound of her neck showed a mass on the left side and MIBI scan diagnosed a parathyroid adenoma which was later pathologically confirmed.