A New Proposed Combined CT and MRI Staging System for Covid-19-Associated Rhino-Orbito-Cerebral Fungal Infection: A Multi-center Study with Pathological Correlation.

RATIONALE AND OBJECTIVES: To propose a combined computed tomography (CT) and magnetic resonance imaging (MRI) based classification system in the management of COVID-19-associated rhino-orbito-cerebral (C-ROC) fungal infection and to assess the reliability of such proposed staging system. MATERIALS AND METHODS: This was a multi-center prospective study conducted on 122 adults with previously confirmed COVID-19 infection. CT and contrast-enhanced MRI (CE-MRI) were performed for all patients. Three radiologists (with experience of 8, 10, and 14 years) independently assessed all images. Then, each patient was assigned a radiological stage based on the five stages of the proposed system according to the radiological extent of the fungal infection. The intra-class correlation coefficient (ICC) test assessed the inter-rater agreement. Based on the pathological evaluation of post-operative specimens, a diagnosis of fungal infection was documented. RESULTS: The most prevalent severity stage among all raters was stage IV in 29.5-31.1% patients. The overall inter-rater agreement of the proposed staging system was excellent (ICC 0.971, 95% CI;0.960-0.979). Moreover, the most common detected pathogen was Mucormycosis (n = 87, 71.3%). Furthermore, there was a statistically significant association between the patients' outcome and the severity stage (P value 0.001) and there was no statistically significant association between ethmoid and sphenoid sinus affection and cranial extension (P value 0.081). CONCLUSION: Our proposed combined CT and MRI severity staging system has a high inter-rater agreement. Moreover, it can aid in the early detection of the C-ROC fungal infection, improve preoperative planning, and subsequently improve the patient's outcome.

Breast Milk Mesenchymal Stem Cells and/or Derived Exosomes Mitigated Adenine-Induced Nephropathy via Modulating Renal Autophagy and Fibrotic Signaling Pathways and Their Epigenetic Regulations.

Chronic kidney disease (CKD), a global health concern, is highly prevalent among adults. Presently, there are limited therapeutic options to restore kidney function. This study aimed to investigate the therapeutic potential of breast milk mesenchymal stem cells (Br-MSCs) and their derived exosomes in CKD. Eighty adult male Sprague Dawley rats were randomly assigned to one of six groups, including control, nephropathy, nephropathy + conditioned media (CM), nephropathy + Br-MSCs, nephropathy + Br-MSCs derived exosomes (Br-MSCs-EXOs), and nephropathy + Br-MSCs + Br-MSCs-EXOs. Before administration, Br-MSCs and Br-MSCs-EXOs were isolated, identified, and labeled with PKH-26. SOX2, Nanog, and OCT3/4 expression levels in Br-MSCs and miR-29b, miR-181, and Let-7b in both Br-MSCs and Br-MSCs-EXOs were assayed. Twelve weeks after transplantation, renal function tests, oxidative stress, expression of the long non-coding RNA SNHG-7, autophagy, fibrosis, and expression of profibrotic miR-34a and antifibrotic miR-29b, miR-181, and Let-7b were measured in renal tissues. Immunohistochemical analysis for renal Beclin-1, LC3-II, and P62, Masson trichome staining, and histopathological examination of kidney tissues were also performed. The results showed that Br-MSCs expressed SOX2, Nanog, and OCT3/4, while both Br-MSCs and Br-MSCs-EXOs expressed antifibrotic miR-181, miR-29b, and Let-7b, with higher expression levels in exosomes than in Br-MSCs. Interestingly, the administration of Br-MSCs + EXOs, EXOs, and Br-MSCs improved renal function tests, reduced renal oxidative stress, upregulated the renal expression of SNHG-7, AMPK, ULK-1, Beclin-1, LC3, miR-29b, miR-181, Let-7b, and Smad-7, downregulated the renal expression of miR-34a, AKT, mTOR, P62, TGF-ß, Smad-3, and Coli-1, and ameliorated renal pathology. Thus, Br-MSCs and/or their derived exosomes appear to reduce adenine-induced renal damage by secreting antifibrotic microRNAs and potentiate renal autophagy by modulating SNHG-7 expression.

Toxoplasma gondii Suppresses Th2-Induced by Trichinella spiralis Infection and Downregulates Serine Protease Genes Expression: A Critical Role in Vaccine Development.

Background: Toxoplasma gondii coinfection can modify host immune responses and the severity and spread of other parasites. We investigated how T. gondii and Trichinella spiralis infections counter-regulate each other's immune responses. Methods: The parasite burden, the expression of T. gondii rhoptry kinase ROP18 and T. spiralis putative serine protease (TsSP), the IgG1 and IgG2a responses, besides histopathological and immunohistochemical staining with iNOS and arginase were used to evaluate the dynamics of coinfection. Results: Through their effects on host immune responsiveness, coinfection with T. gondii modified the virulence of T. spiralis infection. Coinfected animals with high and low doses of T. gondii demonstrated significant reductions in the T. spiralis burden of 75.2% and 68.2%, respectively. TsSP expression was downregulated in both groups by 96.2% and 86.7%, whereasROP18 expression was downregulated by only 6% and10.6%, respectively. In coinfected mice, elevated levels of T. gondii-specific IgG2a antibodies were detected. Th1 induced by T. gondii inhibits the Th2 response to T. spiralis in coinfected animals with high iNOS expression andlow-arginine1 expression. Conclusion: T. gondii infection induces a shift toward a Th1-type immune response while suppressing a helminth-specific Th2 immune response, paving the way for developing novel vaccines and more efficient control strategies.