COPD Patients Exhibit Distinct Gene Expression, Accelerated Cellular Aging, and Bias to M2 Macrophages.

COPD, one of world's leading contributors to morbidity and mortality, is characterized by airflow limitation and heterogeneous clinical features. Three main phenotypes are proposed: overlapping asthma/COPD (ACO), exacerbator, and emphysema. Disease severity can be classified as mild, moderate, severe, and very severe. The molecular basis of inflammatory amplification, cellular aging, and immune response are critical to COPD pathogenesis. Our aim was to investigate EP300 (histone acetylase, HAT), HDAC 2 (histone deacetylase), HDAC3, and HDAC4 gene expression, telomere length, and differentiation ability to M1/M2 macrophages. For this investigation, 105 COPD patients, 42 smokers, and 73 non-smoker controls were evaluated. We identified a reduced HDAC2 expression in patients with mild, moderate, and severe severity; a reduced HDAC3 expression in patients with moderate and severe severity; an increased HDAC4 expression in patients with mild severity; and a reduced EP300 expression in patients with severe severity. Additionally, HDAC2 expression was reduced in patients with emphysema and exacerbator, along with a reduced HDAC3 expression in patients with emphysema. Surprisingly, smokers and all COPD patients showed telomere shortening. COPD patients showed a higher tendency toward M2 markers. Our data implicate genetic changes in COPD phenotypes and severity, in addition to M2 prevalence, that might influence future treatments and personalized therapies.

Analysis of filaggrin 2 gene polymorphisms in patients with atopic dermatitis.

BACKGROUND: Polymorphisms of the filaggrin 2 gene (rs 12568784 and rs 16899374) are associated with persistent atopic dermatitis in African American patients. Filaggrin 2 is a protein with a function similar to filaggrin and also encoded in the epidermal differentiation complex on chromosome 1q21. OBJECTIVE: To evaluate the polymorphisms in the filaggrin 2 gene (rs 12568784 and rs 16899374) in children and adults with atopic dermatitis and to verify the association of these with the severity of the clinical picture, presence of other allergic diseases, and socio-demographic factors. METHOD: The study was carried out with patients and control group. Questionnaires were used to evaluate ethnicity, sex, age, family history, scoring, atopic dermatitis (SCORAD), among other parameters. Genotyping of the filaggrin 2 gene was performed by real-time polymerase chain reaction. RESULTS: Forty-eight patients and 83 controls were evaluated. No correlation was found between the variables studied in patients with atopic dermatitis and polymorphisms, no significant difference between the prevalence of polymorphisms in the patients and in the control group p>0.05. STUDY LIMITS: The exclusive use of self-reported ethnicity information and the sample size. RESULTS: The results of this work can be an incentive for the study of the polymorphisms in atopic dermaititis, considering the characteristic of the Brazilian multi ethnic population. CONCLUSION: This is an unpublished work in Brazil and the first study in the world to have a control group to evaluate alterations in the gene of filaggrin 2.

Analysis of filaggrin 2 gene polymorphisms in patients with atopic dermatitis

Abstract Background: Polymorphisms of the filaggrin 2 gene (rs 12568784 and rs 16899374) are associated with persistent atopic dermatitis in African American patients. Filaggrin 2 is a protein with a function similar to filaggrin and also encoded in the epidermal differentiation complex on chromosome 1q21. Objective: To evaluate the polymorphisms in the filaggrin 2 gene (rs 12568784 and rs 16899374) in children and adults with atopic dermatitis and to verify the association of these with the severity of the clinical picture, presence of other allergic diseases, and socio-demographic factors. Method: The study was carried out with patients and control group. Questionnaires were used to evaluate ethnicity, sex, age, family history, scoring, atopic dermatitis (SCORAD), among other parameters. Genotyping of the filaggrin 2 gene was performed by real-time polymerase chain reaction. Results: Forty-eight patients and 83 controls were evaluated. No correlation was found between the variables studied in patients with atopic dermatitis and polymorphisms, no significant difference between the prevalence of polymorphisms in the patients and in the control group p > 0.05. Study limits: The exclusive use of self-reported ethnicity information and the sample size. Results: The results of this work can be an incentive for the study of the polymorphisms in atopic dermaititis, considering the characteristic of the Brazilian multi ethnic population. Conclusion: This is an unpublished work in Brazil and the first study in the world to have a control group to evaluate alterations in the gene of filaggrin 2.

Insulin resistance impairs cutaneous wound healing in mice.

Obesity is associated with significant changes in skin combined with metabolic alterations such as insulin resistance. Our aim was to investigate the effects of insulin resistance induced by a high-fat diet on cutaneous wound healing. Male C57BL/6 mice were fed standard chow (SC group) or high-fat chow (HFC group) for 30 weeks. On day 0 (28th week), an excisional wound was performed. After 14 days (30th week), the mice were euthanized. Starting from the 8th week, the HFC group had a higher body weight. The HFC group became intolerant to glucose, resistant to insulin, and presented increased plasma cholesterol and triglyceride levels. The wound area was greater in the HFC group. The inflammatory infiltrate and the amount of "fibroblast-like" cells increased in superficial regions of the lesions in the HFC group. The collagen fibers were more organized and denser in the SC group. Hydroxyproline levels were lower in the HFC group. The nitric oxide synthase-2-positive cells were higher in the HFC group. Lipid peroxidation and protein carbonyl levels were higher in the HFC group. The expression levels of alpha-smooth muscle actin and transforming growth factor-ß were higher in the HFC group. These findings support the hypothesis that insulin resistance leads to delayed cutaneous wound healing.

Efeitos de uma dieta hiperlipídica e de uma droga anti-inflamatória não-esteróide inibidora seletiva da ciclooxigenase-2 sobre a cicatrização cutânea de ratos Wistar propensos e resistentes a obesidade / Effects of a high fat diet and an anti-inflammatory drug non steroidal inhibitor selective of cyclooxygenase-2 on the cutaneous wound healing Wistar rats likely resistant to obesity

O sobrepeso induzido por uma dieta rica em gordura atrasa a cicatrização através do prolongamento da fase inflamatória, entretanto, quando recebem uma dieta obesogênica, alguns ratos são suscetíveis a desenvolver sobrepeso, enquanto outros são resistentes. Drogas anti-inflamatórias não-esteróides são frequentemente utilizadas para reduzir a inflamação. Este estudo investigou a cicatrização cutânea em ratos propensos a obesidade induzida por dieta (DIO) e em ratos resistentes a dieta (DR) e avaliou a participação da administração do celecoxibe na cicatrização cutânea destes animais. Ratos machos foram alimentados com uma dieta padrão (Controle, C) ou com uma dieta rica em gordura saturada (30%). Após 19 semanas, o grupo experimental foi subdividido nos grupos DIO e DR. Uma lesão excisional foi feita e os animais foram mortos 7 ou 14 dias depois. Os grupos tratados receberam uma dose diária de 5 ou 10 mg/kg/dia de celecoxibe a partir de dois dias antes da lesão até 7 dias após a lesão, quando foram mortos. O peso corporal foi maior no grupo DIO comparado aos grupos C e DR. A gordura retroperitoneal foi maior no grupo DIO do que nos grupos C e DR e foi maior no grupo DR do que no grupo C. O tratamento com o celecoxibe não alterou o maior peso corporal apresentado pelo grupo DIO ou a maior porcentagem de gordura retroperitoneal apresentada pelos grupos DIO e DR. Todos os grupos tratados com celecoxibe 10 mg apresentaram atraso na cicatrização e não foram mais analisados. O grupo DIO apresentou intolerância a glicose, e ambos os grupos DIO e DR apresentaram atraso na contração e na reepitelização da lesão. O tratamento com celecoxibe 5 mg reverteu a intolerância a glicose no grupo DIO e a contração atrasada nos grupos DIO e DR. Comparado ao grupo DR, o grupo DIO apresentou maior quantidade de células inflamatórias, assim como maiores níveis de peroxidação lipídica. O tratamento com celecoxib (5 mg) não reduziu o número de PMN, mas reduziu o número de mastócitos...

Overweight induced by high-fat diet delays wound healing through elongation of inflammatory phase, however, when receiving on obesogenic diet, some rats are susceptible to developing the overweight phenotype, whereas others are resistant. Nonsteroidal anti-inflammatory drugs are frequently used to reduce the inflammation. This study investigated cutaneous wound healing in diet-induced obesity (DIO)-prone and diet-resistant (DR) rats and evaluated the contribution of celecoxib administration on cutaneous wound healing of these animals. Male rats were fed with a standard (Control, C) or high-saturated fat (30%) diet. After 19 weeks, experimental group was subdivided into DIO and DR groups. An excisional lesion was made and the animals were killed 7 or 14 days later. Treated groups received a daily dose of celecoxib 5 or 10 mg/kg/day from two days before wounding until 7 days after wounding when were killer. The body weight was higher in the DIO group compared to the C and DR groups. Retroperitoneal fat was higher in the DIO group than in the C and DR groups and was higher in the DR group than in the C group. Celecoxib-treatment did not alter the higher body weight presented by DIO group of higher retroperitoneal fat percentage displayed by DIO and DR groups. All groups treated with celecoxib 10 mg showed delayed wound healing, and weren't further analysed. The DIO group presented glucose intolerance, and both the DIO and DR groups presented delayed wound contraction and re-epithelialisation. The celecoxib 5 mg-treatment reversed the glucose intolerance in the DIO group and the delayed contraction in the DIO and DR groups. Compared to the DR group, the DIO group displayed higher amounts of inflammatory cells as well as higher levels of lipid peroxidation. Celecoxib-treatment (5 mg) did not reduce the number of PMN, but reduce mast cells number in DIO group and macrophages number and lipid peroxidation in both groups. Myofibroblastic differentiation...

Effects of supplementation with different edible oils on cutaneous wound healing.

Fatty acids are bioactive molecules, but their effects on cutaneous wound healing are not well understood. Our aim was to investigate the effects of supplementation with edible oils on cutaneous healing. Thirty days before wounding, rats were started on daily supplements of sunflower oil, linseed oil, fish oil, or water. Supplementation lasted until euthanasia. On day 0, an excisional wound was made on the back of each animal. Fourteen days later, the animals were euthanized, and the wound and adjacent skin were collected. Wound closure was higher in the control group compared with the other groups at days 7 and 14. Inflammatory cells were abundant in the control, linseed, and fish groups, but scarce in the sunflower group. Large numbers of myofibroblasts were observed in the control and sunflower groups. The linseed and fish groups presented a high density of dilated blood vessels. The control and sunflower groups showed a moderate density of collagen fibers; a high density of fibers was observed in the linseed and fish groups. Hydroxyproline levels were lowest in the control and sunflower groups. Supplementation with different types of edible oils delayed wound closure and affected the inflammatory infiltrate and collagen deposition.

Quantification of mast cells and blood vessels in the skin of patients with cutaneous mucinosis.

Recent studies have suggested that mast cell numbers are increased in the skin of patients with cutaneous mucinosis and that these cells may have an important role in angiogenesis and production of mucin. Then, skin biopsies from 30 patients with cutaneous mucinosis (papular mucinosis, focal mucinosis, and mucinosis associated with lupus erythematosus) and from 10 healthy subjects were analyzed. Mast cells and blood vessels were immunolabeled with anti-tryptase and anti-CD34 antibodies, respectively, and then quantified stereologically. Counting was performed in papillary and reticular dermis. An increase in the number of mast cells was observed in the skin of patients with cutaneous mucinosis compared with the control group. Only minimal differences were observed in vessel stereology. There was no correlation between the increase in the number of mast cells and the number of blood vessels in the patients studied. There was no significant difference in the numbers of mast cells or blood vessels between the 3 subgroups of cutaneous mucinosis. Although many clinical forms of mucinosis have been described, neither mast cell number nor vessel distribution seems to distinguish the 3 different forms studied here.