A framework to identify functional interactors that contribute to disrupted early retinal development in Vsx2 ocular retardation J mice.

BACKGROUND: A goal of developmental genetics is to identify functional interactions that underlie phenotypes caused by mutations. We sought to identify functional interactors of Vsx2, which when mutated, disrupts early retinal development. We utilized the Vsx2 loss-of-function mouse, ocular retardation J (orJ), to assess interactions based on principles of positive and negative epistasis as applied to bulk transcriptome data. This was first tested in vivo with Mitf, a target of Vsx2 repression, and then to cultures of orJ retina treated with inhibitors of Retinoid-X Receptors (RXR) to target Rxrg, an up-regulated gene in the orJ retina, and gamma-Secretase, an enzyme required for Notch signaling, a key mediator of retinal proliferation and neurogenesis. RESULTS: Whereas Mitf exhibited robust positive epistasis with Vsx2, it only partially accounts for the orJ phenotype, suggesting other functional interactors. RXR inhibition yielded minimal evidence for epistasis between Vsx2 and Rxrg. In contrast, gamma-Secretase inhibition caused hundreds of Vsx2-dependent genes associated with proliferation to deviate further from wild-type, providing evidence for convergent negative epistasis with Vsx2 in regulating tissue growth. CONCLUSIONS: Combining in vivo and ex vivo testing with transcriptome analysis revealed quantitative and qualitative characteristics of functional interaction between Vsx2, Mitf, RXR, and gamma-Secretase activities.

Enterovesical fistula as an iatrogenic complication of foley catheter use: A case report.

Enterovesical fistulas can represent a rare complication of long-term indwelling urinary catheters. It can lead to significant morbidity and mortality and usually requires emergent intervention. An elderly nursing home resident presented with abdominal pain and fecal matter in her urine. She was found to have a foley catheter bulb in the small bowel and successfully underwent open repair of the bladder defect along with partial small bowel resection. The diagnosis and management of Enterovesical fistulas as an iatrogenic complication of Foley catheter use is discussed.

Hidradenitis Suppurativa: Consequences of Microbiome Dysbiosis on Immune Dysregulation and Disease Severity.

Hidradenitis suppurativa (HS) is a chronic inflammatory condition characterized by the formation of nodules, abscesses, and sinus tracts with tunnels that primarily involves the skin folds. HS affects approximately 1% of the population, but its pathogenesis is unclear. Dysbiosis of skin microbiome is a major cause of HS and alterations of microbiome composition and diversity can be seen in the skin of patients with HS. These disruptions may contribute to the immune dysfunction seen in HS. Understanding these alterations and their contributions to the pathogenesis of HS could help guide future treatment. In addition to dysbiosis promoting immune dysregulation, HS may promote dysbiosis via differences in expression of antimicrobial peptides (AMPs). In this review, we have discussed the role of skin and gut microbiome in manifestation of HS and the consequences of dysbiosis on the immune system.

Toll-Like Receptor-4 Antagonist Enhances the Repair of Ultraviolet Radiation-Induced DNA Damage and Augments Anti-Tumor Immune Responses in Mice.

Ultraviolet (UV) irradiation of the skin is related to the development of skin cancer. UVB also causes DNA damage in the form of cyclobutane pyrimidine dimers (CPDs), which can result in stable mutations. Toll-like receptor 4 (TLR4), a component of innate immunity, plays a key role in cancer. Previous studies from our laboratory have observed that TLR4 deficiency resulted in the repair of UVB-induced DNA damage, inhibition of UVB-induced immune suppression, and carcinogenesis. In this study, we determined the efficacy of TLR4 antagonist TAK-242 in regulation of UVB-induced DNA damage, inflammation, and tumor development. Our results indicate that TAK-242 treatment increased the expression of xeroderma pigmentosum group A (XPA) mRNA, resulting in the repair of UVB-induced CPDs in skin of SKH-1 mice. Treatment with TAK-242 also inhibited the activation of NLR family pyrin domain containing 3 (NLRP3) in UVB-exposed skin of SKH-1 mice. Cutaneous carcinogenesis was significantly reduced in mice treated with TAK-242 in comparison to vehicle-treated mice. The proinflammatory cytokines IL-1ß, IL-6, and TNF-α were also found to be significantly greater in vehicle-treated mice than TAK-242-treated mice. Finally, treatment with TAK-242 augmented anti-tumor immune responses in mice. Our data provide further evidence that activation of the TLR4 pathway promotes the development of UV-induced non-melanoma skin cancer mediated at least in part on its negative effects on DNA damage. Moreover, treatment with the TLR4 inhibitor TAK-242 may be effective for prevention of skin cancer.

Study on preparation of the product Vilacid, soluble powder utilized in the treatment of malnutrition

Soluble powder of vilacid was prepared by direct drying spray and addition of inactive components and aromatic compounds. This powder contains high essential total aminoacids and packaged in the suitable dosage

Study on preparing of liquid Vilacid products used in the treatment of malnutrition

Vilacid has 21 amino acids, in which has essential amino acids that help treatment for malnutrition in children, especially treat for children with dyspepsia. Clinical trial treated children of malnutrition suggest that its effect is to increase weight, subcutaneous fat, albumin and serum protein