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Obstructive Sleep Apnea (OSA) is related to repeated upper airway collapse, intermittent hypoxia, and intestinal barrier dysfunction. The resulting damage to the intestinal barrier may affect or be affected by the intestinal microbiota. A prospective case–control was used, including 48 subjects from Sleep Medicine Center of Nanfang Hospital. Sleep apnea was diagnosed by overnight polysomnography. Fecal samples and blood samples were collected from subjects to detect fecal microbiome composition (by 16S rDNA gene amplification and sequencing) and intestinal barrier biomarkers—intestinal fatty acid-binding protein (I-FABP) and D-lactic acid (D-LA) (by ELISA and colorimetry, respectively). Plasma D-LA and I-FABP were significantly elevated in patients with OSA. The severity of OSA was related to differences in the structure and composition of the fecal microbiome. Enriched Fusobacterium, Megamonas, Lachnospiraceae_UCG_006, and reduced Anaerostipes was found in patients with severe OSA. Enriched Ruminococcus_2, Lachnoclostridium, Lachnospiraceae_UCG_006, and Alloprevotella was found in patients with high intestinal barrier biomarkers. Lachnoclostridium and Lachnospiraceae_UCG_006 were the common dominant bacteria of OSA and intestinal barrier damage. Fusobacterium and Peptoclostridium was independently associated with apnea–hypopnea index (AHI). The dominant genera of severe OSA were also related to glucose, lipid, neutrophils, monocytes and BMI. Network analysis identified links between the fecal microbiome, intestinal barrier biomarkers, and AHI. The study confirms that changes in the intestinal microbiota are associated with intestinal barrier biomarkers among patients in OSA. These changes may play a pathophysiological role in the systemic inflammation and metabolic comorbidities associated with OSA, leading to multi-organ morbidity of OSA. [ABSTRACT FROM AUTHOR]

Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder, which causes a range of physical, cognitive, and medical challenges. To retrospectively analyze the clinical characteristics and genetic variations of Chinese patients, and to provide experience for further diagnosis and treatment of CdLS in Chinese children, we identified 15 unrelated Chinese children who presented with unusual facial features, short stature, developmental delay, limb abnormalities, and a wide range of health conditions. In this study, targeted-next generation sequencing was used to screen for causal variants and the clinically relevant variants were subsequently verified using Sanger sequencing. DNA sequencing identified 15 genetic variations, including 11 NIPBL gene variants, two SMC1A gene variants, one RAD21 gene variant, and one HDAC8 variant. The phenotype of these patients was summarized and differences between this cohort and another four groups were compared. The clinical manifestations of the patients in this cohort were mostly consistent with other ethnicities, but several clinical features in our cohort had different frequencies compared with other groups. We identified 15 deleterious variants of which 11 were novel. Variants in the NIPBL gene were the most common cause in our cohort. Our study not only expands upon the spectrum of genetic variations in CdLS, but also broadens our understanding of the clinical features of CdLS. [ABSTRACT FROM AUTHOR]

Bovine lactoferricin (LfcinB) has potent antibacterial, antifungal and antiparasitic activities but is also hemolytic. Our objective was to identify LfcinB17-31 derivatives with reduced hemolysis and improved antimicrobial activity via substituting Cys3, Arg4, Gln7, Met10, and Gly14 with more hydrophobic residues. Two peptides, Lfcin4 and Lfcin5, showed higher activity against Staphylococcus aureus and Salmonella enteritidis and lower hemolytic activity than the parent peptide LfcinB17-31. These peptides permeabilized the outer and inner membranes of S. enteritidis; however, Lfcin5 did not permeabilize the inner membrane of S. aureus. Gel retardation and circular dichroism spectra showed that Lfcin4 and Lfcin5 bound to bacterial genomic DNA. Lfcin4 inhibited DNA, RNA and protein synthesis. Both peptides induced the peeling of membranes and the lysis of S. enteritidis. At doses of 10 and 15 mg/kg, Lfcin4 and Lfcin5 reduced the bacterial counts in infected thigh muscles by 0.03-0.10 and 0.05-0.63 log10 CFU/g of tissue, respectively, within 10 h. Lfcin4 and Lfcin5 enhanced the survival rate of endotoxemic mice; reduced serum IL-6, IL-1β and TNF-α levels; and protected mice from lipopolysaccharide-induced lung injury. These data suggest that Lfcin4 and Lfcin5 may be antimicrobial and anti-endotoxin peptides that could serve as the basis for the development of dual-function agents. [ABSTRACT FROM AUTHOR]