Unveiling the interplay between NSAID-induced dysbiosis and autoimmune liver disease in children: insights into the hidden gateway to autism spectrum disorders. Evidence from ex vivo, in vivo, and clinical studies.

Autism spectrum disorders (ASD) represent a diverse group of neuropsychiatric conditions, and recent evidence has suggested a connection between ASD and microbial dysbiosis. Immune and gastrointestinal dysfunction are associated with dysbiosis, and there are indications that modulating the microbiota could improve ASD-related behaviors. Additionally, recent findings highlighted the significant impact of microbiota on the development of autoimmune liver diseases, and the occurrence of autoimmune liver disease in children with ASD is noteworthy. In the present study, we conducted both an in vivo study and a clinical study to explore the relationship between indomethacin-induced dysbiosis, autoimmune hepatitis (AIH), and the development of ASD. Our results revealed that indomethacin administration induced intestinal dysbiosis and bacterial translocation, confirmed by microbiological analysis showing positive bacterial translocation in blood cultures. Furthermore, indomethacin administration led to disturbed intestinal permeability, evidenced by the activation of the NLRP3 inflammasomes pathway and elevation of downstream biomarkers (TLR4, IL18, caspase 1). The histological analysis supported these findings, showing widened intestinal tight junctions, decreased mucosal thickness, inflammatory cell infiltrates, and collagen deposition. Additionally, the disturbance of intestinal permeability was associated with immune activation in liver tissue and the development of AIH, as indicated by altered liver function, elevated ASMA and ANA in serum, and histological markers of autoimmune hepatitis. These results indicate that NSAID-induced intestinal dysbiosis and AIH are robust triggers for ASD existence. These findings were further confirmed by conducting a clinical study that involved children with ASD, autoimmune hepatitis (AIH), and a history of NSAID intake. Children exposed to NSAIDs in early life and complicated by dysbiosis and AIH exhibited elevated serum levels of NLRP3, IL18, liver enzymes, ASMA, ANA, JAK1, and IL6. Further, the correlation analysis demonstrated a positive relationship between the measured parameters and the severity of ASD. Our findings suggest a potential link between NSAIDs, dysbiosis-induced AIH, and the development of ASD. The identified markers hold promise as indicators for early diagnosis and prognosis of ASD. This research highlights the importance of maintaining healthy gut microbiota and supports the necessity for further investigation into the role of dysbiosis and AIH in the etiology of ASD.

Comparative histological and immunohistochemical study on the effect of platelet rich plasma/minoxidil, alone or in combination, on hair growth in a rat model of androgenic alopecia.

BACKGROUND: Androgenic alopecia (AGA) is the commonest cause of hair loss in men with limited treatment options. AIM OF THE WORK: To compare the efficacy of PRP and minoxidil on experimentally induced AGA in adult male albino rats. MATERIALS AND METHODS: Thirty male albino rats were used. Group I (control group). Group II (AGA group): received testosterone only. Group III: received topical minoxidil. Group IV: received PRP /three days. Group V: received PRP and topical minoxidil. RESULTS: Groups III, IV, and V showed significant increase in mean epidermal thickness, mean numbers of total hair follicles and anagen hair follicles, and decrease in telogen hair follicles compared to AGA group. Group V showed the best results. AGA group showed perifollicular fibrosis and follicular streamers. They were absent in PRP group and group V. Significant decrease of Ki-67 positive cells in AGA. PRP and minoxidil groups showed a significant increase in number of Ki-67 positive cells compared to control and AGA groups. Group V showed the highest number of Ki-67 positive cells. CONCLUSION: PRP was more effective than minoxidil in treatment of experimentally induced AGA in rats. The best results were obtained when PRP and minoxidil were administered together.

A highlight on CD4+ T-cells in the spleen in a rat model of rheumatoid arthritis and possible therapeutic effect of omega-3. Histological and Immunofluorescence study.

BACKGROUND: Rheumatoid arthritis (RA), a primary chronic articular disease with wide range of extra-articular and systemic effects. The spleen is one of the most affected organs in RA. CD4+ T cells play an important role in initiation, maintenance and control of the disease. AIM OF THE WORK: This work was designed to study the histological changes occurring in the spleen in a rat model of RA and to assess the effect of treatment with omega-3 alone, with special refer to the role of CD4+ T-cells. MATERIALS AND METHODS: Thirty male albino rats were divided into four groups; control group, early and progressive RA groups and omega-3 treated group. RA was induced in rats of groups II, III and IV by a single subcutaneous injection of complete Freund's adjuvant (CFA). Samples were taken after two and four weeks of the CFA injection (in early and progressive RA groups respectively). Treatment with omega-3 (300 mg/kg/day in a single, daily oral dose) started two weeks after CFA injection in rats of group IV and continued for another two weeks. Spleen specimens were collected at the appropriate times and processed to obtain paraffin blocks. Sections were then stained for histological and immunofluorescence studies. RESULTS: Both, early and progressive RA induced noticeable structural changes in the spleen. Thickened capsule and trabeculae and marked congestion of the blood sinusoids of the red pulp were evident. Expansion of the white pulp and areas of mononuclear cellular infiltration were seen, especially in progressive RA. Affection of blood vessel walls was also noticed. Immunofluorescence study showed extensive expression of Anti-CD4 Monoclonal Antibodies especially in progressive RA. Treatment with omega-3 significantly improved the structure of the spleen as detected by both histological and immunofluorescence studies. CONCLUSION: Omega-3 treatment ameliorated the structural damage of the spleen caused by experimental induction of RA.