ABSTRACT
Skin wound healing tends to slow down with aging, which is detrimental to both minor wound recovery in daily life and the recovery after surgery. The aim of current study was to explore the effect of histone deacetylase 6 (HDAC6) on wound healing during aging. Cultured human dermal fibroblasts (HDFs) and mouse full-thickness skin wound model were used to explore the functional changes of replicative senescent dermal fibroblasts and the effect of aging on skin wound healing. Scratch wound healing assay revealed significantly decreased migration speed of senescent HDFs, and BrdU incorporation assay indicated their considerably retardant proliferation. The protein expression levels of collagen and HDAC6 were significantly decreased in both senescent HDFs and skin tissues from aged mice. HDAC6 activity inhibition with highly selective inhibitor tubastatin A (TsA) or HDAC6 knockdown with siRNA decreased the migration speed of HDFs and considerably suppressed fibroblast differentiation induced by transforming growth factor-β1 (TGF-β1), which suggests the involvement of HDAC6 in regulating fundamental physiological activities of dermal fibroblasts. In vivo full-thickness skin wound healing was significantly delayed in young HDAC6 knockout mice when compared with young wild type mice. In addition, the wound healing was significantly slower in aged wild type mice than that in young wild type mice, and became even worse in aged HDAC6 knockout aged mice. Compared to the aged wild type mice, aged HDAC6 knockout mice exhibited delayed angiogenesis, reduced collagen synthesis, and decreased collagen deposition in skin wounds. Together, these results suggest that delayed skin wound healing in aged mice is associated with impaired fibroblast function. Adequate expression and activity of HDAC6 are required for fibroblasts migration and differentiation.
Subject(s)
Humans , Animals , Mice , Aged , Histone Deacetylase 6 , Skin , Wound Healing , Cell Movement , Collagen/pharmacology , Fibroblasts , Mice, Knockout , Cells, CulturedABSTRACT
OBJECTIVE@#To investigate the clinical and genetic characteristics of a family with hereditary spherocytosis (HS), to clarify the cause of the disease, and to provide the basis for genetic counseling and prenatal diagnosis.@*METHODS@#The clinical data of proband and his parents were collected, and HS-related pathogenic genovariation of the proband was detected by high throughput sequencing. Suspected pathogenic mutation sites were verified by PCR-Sanger sequencing, and the fetus were conceived by a proband mother underwent prenatal diagnosis.@*RESULTS@#Clinical manifestations of the proband showed moderate anemia, mild splenomegaly, and jaundice (an indirect increase of bilirubin). The gene detection showed that the proband showed compound heterozygous mutations of SPTB gene c. 6095T > C (p.Leu2032Pro) and c. 6224A > G (p.Glu2075Gly), which was inherited from the asymptomatic mother and father, respectively. Both mutations were detected rarely in the common population. Prenatal diagnosis revealed that the fetus inherited a mutant gene of the mother.@*CONCLUSION@#The compound heterozygous mutations of SPTB genes c.6095T>C (p.Leu2032Pro) and c.6224A>G (p.Glu2075Gly) were the causes of the family disease, which provides a basis for family genetic counseling and prenatal diagnosis. This report is the first one found in the HGMD,1000G and EXAC database, which provides an addition to the mutation profile of the SPTB gene.
Subject(s)
Female , Humans , Infant, Newborn , Male , Pregnancy , Genetic Testing , High-Throughput Nucleotide Sequencing , Mutation , Pedigree , Prenatal Diagnosis , Spectrin/genetics , Spherocytosis, Hereditary/geneticsABSTRACT
OBJECTIVE: To observe the rehabilitation effect of non-invasive positive pressure ventilation( NPPV) in treating pneumoconiosis patients with pulmonary dyspnea. METHODS: A retrospective analysis was used to analyze the treatment compliance,treatment time,treatment effect and adverse reactions of 295 pneumoconiosis patients who had undergone inpatient NPPV treatment. RESULTS: The median of NPPV treatment time of 295 pneumoconiosis patients was 14( 1-281)days. The treatment compliance rate was 79. 66 %( 235 /295). The dyspnea improvement rate was 73. 22 %( 216 /295).The Chi-square test results showed that the dyspnea improvement rate increased with the prolonged treatment time( P <0. 01). Among these,the dyspnea improvement rates of groups with treatment time of 10 days,20 days and ≥ 30 days were higher than group with treatment time < 10 days,the dyspnea improvement rate of the group with treatment time ≥30days was higher than 10 days group( P < 0. 01). The incidence of adverse reactions was 7. 12 %. CONCLUSION: NPPV treatment could improve dyspnea symptoms of pneumoconiosis patients with less adverse reaction.