Phenotypic heterogeneity in family members of patients with retinitis pigmentosa

Purpose: To describe the phenotypic variations in family members of patients with retinitis pigmentosa (RP) with different modes of inheritance and to assess the ocular abnormalities in RP families. Methods: A descriptive analysis of three types of inheritance of RP was carried out, where 64 family members were examined at a tertiary eye care center, South India. They underwent comprehensive eye examination, fundus photography, fundus autofluorescence (FAF), full?field electroretinogram (FFERG), and spectral domain optical coherence tomography (SD?OCT). Analysis was performed between mild and severe forms of abnormalities to delineate retinal structural and functional defects in RP families. Results: The mean age was 38.55 ± 17.95 years. Males were 48.4%. In autosomal recessive and X?linked recessive groups, 74.2% and 77.3%, respectively, were asymptomatic, whereas in autosomal dominant group, 27.3% were asymptomatic. The proportion of the cases with abnormalities in all three groups was higher on ERG (59.6%), followed by OCT (57.5%), visual acuity (43.7%), peripheral FAF (23.5%), and macular FAF (11.8%). However, these abnormalities and the clinical pictures of the family members had no statistical difference across the three groups of inheritance. Conclusion: Structural and functional retinal alterations were noted in four out of five asymptomatic members, suggesting the need for careful screening of RP families and the pressing need for pre?test (genetic) counseling

Orlistat induces ferroptosis-like cell death of lung cancer cells / 医学前沿

Aberrant de novo lipid synthesis is involved in the progression and treatment resistance of many types of cancers, including lung cancer; however, targeting the lipogenetic pathways for cancer therapy remains an unmet clinical need. In this study, we tested the anticancer activity of orlistat, an FDA-approved anti-obesity drug, in human and mouse cancer cells in vitro and in vivo, and we found that orlistat, as a single agent, inhibited the proliferation and viabilities of lung cancer cells and induced ferroptosis-like cell death in vitro. Mechanistically, we found that orlistat reduced the expression of GPX4, a central ferroptosis regulator, and induced lipid peroxidation. In addition, we systemically analyzed the genome-wide gene expression changes affected by orlistat treatment using RNA-seq and identified FAF2, a molecule regulating the lipid droplet homeostasis, as a novel target of orlistat. Moreover, in a mouse xenograft model, orlistat significantly inhibited tumor growth and reduced the tumor volumes compared with vehicle control (P < 0.05). Our study showed a novel mechanism of the anticancer activity of orlistat and provided the rationale for repurposing this drug for the treatment of lung cancer and other types of cancer.

Effects of faf1 gene knockout by CRISPR/Cas9 on zebrafish cartilage and sarcomere development / 第三军医大学学报

Objective To determine the effect of knocking down zebrafish faf1 gene by CRISPR/Cas9 editing technique.Methods gRNA was designed and prepared for the faf1 gene of zebrafish,and gRNA was mixed with Cas9 mRNA by microinjection into zebrafish single cell embryos.The mutant F0 generation zebrafish was screened out by enzyme digestion and gene sequencing.The mutant F0 was genetically outcrossed with the wild-type zebrafish to get the F1 heterozygous zebrafish,and the genotype of zebrafish was detected by microscopic observation.Results The faf1 gRNA and Cas9 mRNA were successfully prepared.The gRNA (gRNA6) located in the exon 6 of faf1 could shift the faf1 gene into frameshift mutations.The mutation type MU1 was screened out and the somatic cytochrome deposition delay was observed in this heterozygous zebrafish.At 4 d post fertilization (dpf),there were sarcomeric dysplasia and head shrinkage,increased hyoid angle and other craniofacial cartilage deformities.And the zebrafish died at 8 ～9 dpf.Conclusion CRISPR/Cas9 knocking out thefaf1 gene produces a new phenotype for zebrafish,with delayed pigment deposition and nodule-like change in tail muscle section.

Expression of Fas-associated Factor 1 in the Developing Testis / 체질인류학회지

FAS associated factor 1 (FAF1) is a Fas-associating molecule, which enhances Fas mediated apoptosis. FAF1 gene is expressed most abundantly in the testis among the mouse organs. The aim of this study was to reveal the expression and the role of FAF1 in the developing testis. H-E stain and FAF1 immunohistochemistry were performed in the testis and epididymis of the E15.5 embryo, and 1, 2, and 8 week-old C57/BL6 mice. FAF1 was expressed in the testis from E 15.5 embryo to 8 week-old mice. Cell type of FAF1 positive cells was different among the developmental stage. Furthermore, cellular (cytoplasmic or nuclear) localization of FAF1 in the male germ cells was different during the developmental stage. FAF1 was expressed mainly in the nuclei of the germ cells 1 and 8 weeks after birth, when cell differentiation occurs actively in the testis. However, FAF1 was expressed in the cytoplasms of germ cells 2 weeks after birth, when apoptosis occurs maximally in the testis. Taken together, it can be suggested FAF1 expressed in male germ cells in the testis. FAF1 might be involved in regulation of the cellular function during spermatogenic cell differentiation and apoptosis in the testis.

Uso masivo de la coproparasitoscopía con FAF / Masive use of coproparasitoscopy with FAF

El uso de solución preservadora y fijadora (FAF) de formas parásitas en la coproparasitoscopía de rutina para el diagnóstico de parasitosis intestinales, es considerado en este trabajo como la parte escencial para la realización de encuestas y trabajos de campo, cuando se desea tener una mayor confiabilidad, así como cuando se tienen que transportar lals muestras a un laboratorio de concentración. Su uso continuo ahorra material y equipo, y es adecuado para el procesamiento de los exámenes que más comunmente solicita el cliente