A prospective observational study correlating possible novel biomarkers with disease severity and antihistamine response in chronic spontaneous urticaria.

Background: Role of complement fraction 5a (C5a), interleukin (IL)-9, and apolipoprotein (apo) A-IV as biomarkers of disease severity and antihistamine response in chronic spontaneous urticaria (CSU) remains elusive. Objective: To identify the role of C5a, IL-9, and apo A-IV as potential biomarkers in predicting disease severity and antihistamine response in CSU patients. Methods: This was a prospective observational study of 95 patients and 42 controls. Serum analysis of C5a, IL-9, and apo A-IV was done using enyzme linked immunosorbent assay kits. Also, serum IgE and anti-thyroid peroxidase (TPO) levels were assessed in all patients. All patients were started on oral levocetirizine 5 mg at baseline and dose was titrated upwards to maximum of 20 mg based on response. Patients were categorized into antihistamine responders or nonresponders as per their disease response. Serological markers, serum IgE, and anti-TPO were correlated with baseline disease severity and antihistamine response. Results: C5a levels were significantly higher in cases as compared to controls (P = 0.004). Significantly higher IL-9 levels were observed in antihistamine responders than nonresponders (P = 0.008). Baseline urticaria severity demonstrated a statistically significant positive and negative correlations with IL-9 (ρ = 0.277, P = 0.007) and apo A-IV (ρ = -0.271, P = 0.008) levels, respectively. Levels of serum IgE (P = 0.031) and anti-TPO (P = 0.039) were significantly higher in antihistamine nonresponders compared to responders. Conclusions: IL-9 and apo A-IV might be potential novel biomarkers to predict urticaria severity. Higher IL-9 might be a predictor of antihistamine response. Elevated anti-TPO and serum IgE might predict poor antihistamine response.

Altered levels of lymphocyte enhancer-binding factor-1 modulates the pigmentation in acral and non-acral lesions of non-segmental vitiligo patients: a follow-up-based study in North India.

BACKGROUND: Lymphocyte enhancer-binding factor-1 (LEF1) is responsible for melanocyte proliferation, migration and differentiation and its downregulation may result in depigmentation in vitiligo. Narrowband UVB (NB-UVB) phototherapy is known to enhance melanocyte migration from hair follicles to lesional epidermis; hence, it may have a role in the upregulation of LEF1. OBJECTIVES: We intended to assess the expression of LEF1 both before and after NB-UVB therapy and correlate it with the extent of re-pigmentation. MATERIALS AND METHODS: In this prospective cohort study, 30 patients of unstable non-segmental vitiligo were administered NB-UVB phototherapy for 24 weeks. Skin biopsies were obtained from acral and non-acral sites in all patients, both prior to initiation and after completion of phototherapy and LEF1 expression was measured. RESULTS: Amongst the 16 patients who completed the study, at 24 weeks, all patients achieved > 50% re-pigmentation. However, > 75% re-pigmentation was achieved in only 11.1% of acral patches, whereas it was achieved in a significantly higher number of non-acral patches (66.6%) (p = 0.05). A significant increase was observed in the mean fluorescent intensity of the LEF1 gene in both acral as well as non-acral areas at 24 weeks as compared to baseline (p = 0.0078), However, no difference was observed between acral and non-acral lesions in the LEF1 expression at 24 weeks or the change in LEF1 expression from baseline. CONCLUSION: LEF1 expression modulates the re-pigmentation of vitiligo lesions after treatment with NBUVB phototherapy.

Melanocyte Adhesion and Apoptosis in Vitiligo: Linking Puzzle Blocks.

Vitiligo is the utmost common depigmenting condition consequential from melanocyte loss from the basal layer of the epidermis. Vitiligo disease mostly affects dark-skinned races and makes them more sensitive to UV radiation. It is also linked with some autoimmune diseases and various psychosocial difficulties. Melanocyte loss leads to depigmentation in vitiligo, is a major concern over decades, and even affects an individual's day-to-day life severely. All the theories, including autoimmune, autocytotoxic, and neural, collectively decipher either prime impact on the melanogenesis inhibition or deficient adhesion inspired melanocytes disappearance. Previously it has been described that melanocyte loss in vitiligo patients is caused by defective adhesion. Melanocyte death by apoptosis mainly occurs due to melanocyte detachment or migration from the basal layer and further followed by transepidermal migration. Various cell surface molecules, i.e., cell adhesion molecules (CAMs) in affiliation with neighbouring cells and extracellular matrix (ECM), encompass a typical cell adhesion process. All these ECM molecules along with transcription factors, help in the survival and maintenance of pigmentary cells/melanocytes. Therefore, in this issue, we have tried to compile the literature available on melanocyte detachment/apoptosis in ECM due to the alteration in adhesion molecules and matrix metalloproteinases (MMPs) driven by known/unknown transcription factors.

Electrofulguration-assisted dermabrasion is comparable to manual dermabrasion in patients undergoing autologous non-cultured epidermal cell suspension for treatment of stable vitiligo: A randomized controlled trial.

BACKGROUND: Recipient site preparation is a crucial step in non-cultured epidermal cell suspension (NCES) as it facilitates proper uptake of the grafted melanocytes. OBJECTIVES: To compare the repigmentation rate of recipient sites prepared with manual dermabrasion (MD) versus electrofulguration-assisted dermabrasion (EF) in patients undergoing NCES for treatment of stable vitiligo. METHODS: This was a prospective randomized study including 26 patients of stable vitiligo (VIDA 0 or -1), each having two patches of size greater than 3 × 3 cm located symmetrically or at the same site or a single patch of 6 × 6 cm or larger. After randomization of patches in the given patient, MD and EF were performed on recipient areas followed by NCES. The patients were followed up at 4 weekly intervals up to 24 weeks and assessed for extent of repigmentation and adverse effects if any. RESULTS: Greater than 75% repigmentation was observed in 69.3% of the patches prepared by MD as compared to 73.1% patches prepared by EF at the end of 24 weeks (p = 0.791). The mean improvement in target VASI was 64.0% in the MD group as compared to 68.8% in the EF group (p = 0.21). Patches prepared by EF achieved successful repigmentation earlier as compared to patches prepared by MD (9.4 weeks vs 11.4 weeks, p = 0.12). CONCLUSION: Both MD and EF have comparable outcomes with respect to all parameters.

Fatty acid synthase inhibition ameliorates diabetes induced liver injury in rodent experimental model.

The abnormal dietary life style leads to hyperlipidemia and insulin resistance with ectopic lipid accumulation and elevated levels of hepatic glucose development which are the underlying pathological characteristics of fatty liver diseases. The pharmacological inhibition of fatty acid synthase of de novo lipogenesis may regulate the dysfunctional lipid biotransformation and reverse the pathological state of diabetic liver injury. The three pharmacological interventions (PTS; Pterostilbene, ARB; Arbutin, PUR; Purpurin) were administered to manage the condition of diabetic liver injury against the high fat diet (HFD) + Streptozotocin (STZ) 30 mg/kg b.wt. rodent animal model to observe the effect of abnormal fatty acid synthesis. The qRT-PCR was used to evaluate the fatty acid synthase (FASN) expression which is independently allied with diabetes associated fatty liver disorders. To determine the therapeutic potential of three selected drugs, the biochemical parameters and histopathological considerations were utilized. Three subsequent dosage of PTS, ARB and PUR administered (i.e., 30,60 & 120 mg/kg/p.o.) for five weeks significantly alter the serum parameters, oxidative burden in HFD-STZ which, in turn, resulted in diabetic liver injury. It was also revealed that increased mRNA expression of fatty acid synthase (FASN), which is known to promote abnormal fatty acid synthesis through different molecular signaling pathways, was associated with the development of diabetes associated liver injury, this expression was observed to be significantly suppressed by PTS, ARB and PUR treatment. Moreover, the studies of histopathology showed that there was substantial structural improvement after PTS, ARB and PUR treatment. All three selected drugs have been shown to be effective for Diabetic liver injury (DLI) care but PTS shows impressive results compared to other selected drugs.

Clinical, biochemical, and serologic predictors of drug reaction with eosinophilia and systemic symptoms syndrome: A prospective case-control study.

BACKGROUND: Detailed scoring systems such as the European Registry of Severe Cutaneous Adverse Reactions (RegiSCAR) score for validating a diagnosis of drug reaction with eosinophilia and systemic symptoms (DRESS) syndrome are available, but there is no rapid, easy tool to identify DRESS at presentation. OBJECTIVE: To identify the clinical, biochemical, and serologic markers predicting the DRESS syndrome and its severity. METHODS: In this prospective observational study, 25 patients with the DRESS syndrome and 25 control patients with maculopapular drug rash were recruited. Baseline clinical, biochemical, and serologic markers, such as high-sensitivity C-reactive protein (hsCRP), erythrocyte sedimentation rate, and thymus and activation-regulated chemokine (TARC) levels, were recorded and their utility in identifying the DRESS syndrome at presentation and predicting severity was analyzed. RESULTS: The effectiveness of TARC level (>613.25 pg/mL), total body surface area (TBSA, >35%), hsCRP (>5 mg/L), eosinophils (>6%), absolute eosinophil count (>450 cells/mm3), and aspartate transaminase (>92 U/L) were statistically similar to the effectiveness of the RegiSCAR DRESS validation score (≥2) in diagnosing the DRESS syndrome. A combination model (TBSA at baseline, eosinophil count, and hsCRP) at the cutoff of 6.8 had a sensitivity of 96% and a specificity of 100%. Baseline serum TARC levels did not predict the DRESS severity or outcome. LIMITATIONS: Small sample size. CONCLUSION: The combination of TBSA involvement, eosinophil count, and hsCRP levels can predict the DRESS syndrome at presentation.

Coronavirus (COVID-19): A Systematic Review and Meta-analysis to Evaluate the Significance of Demographics and Comorbidities.

Background: The unprecedented outbreak of a contagious respiratory disease caused by a novel coronavirus has led to a pandemic since December 2019, claiming millions of lives. The study systematically reviews and summarizes COVID-19's impact based on symptoms, demographics, comorbidities, and demonstrates the association of demographics in cases and mortality in the United States. Methods: PubMed and Google Scholar were searched from December 2019- August 2020, and articles restricted to the English language were collected following PRISMA guidelines. US CDC data was used for establishing statistical significance of age, sex, and race. Results: Among 3745 patients in China, mean age is 50.63 (95% CI: 36.84, 64.42) years, and 55.7 % (95% CI: 52.2, 59.2) were males. Symptoms included fever 86.5% (82.7, 90.0), fatigue 41.9% (32.7, 51.4), dyspnea 29.0% (21.2, 37.5), cough 66.0% (61.3, 70.6), mucus 66% (61.3, 70.6), lymphopenia 18.9% (5.2, 38.0). Prevalent comorbidities were hypertension 16.4% (12.5, 20.8), diabetes 8.9% (7.0, 11.1), CVD 10.9% (6.1, 16.7), ARDS 14.6% (4.9, 27.8), malignancy 1.5 (0.05, 2.8), 1.3% (0.08, 1.9), COPD 1.3 (0.08, 1.9). 63.5 % (33.5, 88.7) received oxygen therapy, 20.8% (8.9, 35.7) were in ventilation, 23.5% (5.9, 47.8) were at the ICU. 86.5% (76.8, 94) had antiviral, 73.9% (55.3, 89.0) had antibiotics, 30% (20.6, 40.2) corticosteroids treatment.In the US, the odds ratio of infection in males to females is 0.873 (CI: 0.052,14.791), while the odds of dying from infection is 1.378 (CI: 0.081, 23.528) for males. The prevalence of infection is higher in females; case and death rates are higher in whites and Hispanics than other races; the death rate is higher in males irrespective of race and age; death rate per 100,000 population increases monotonically with age. Conclusion: Results showed that metabolic diseases comprising CVD, diabetes, hypertension, and respiratory diseases, including COPD, ARDS, are the most common comorbidities to severe condition and poor prognosis in covid-19 patients. Following the recent FDA's guidance for designing Covid-19 vaccine trials, stratification factors of age, race, sex, and comorbidities need consideration in allocation. This study aimed to provide clinical researchers, health policy planners a detailed insight into the coronavirus disease.

Dendritic cells sub-sets are associated with inflammatory cytokine production in progressive vitiligo disease.

In autoimmune onset of vitiligo, perilesional area shows inflammatory cells including T cytotoxic, helper cells and macrophages. Dendritic Cells (DCs) regulate immune activities by antigen presentation to T cells or cytokine production. It is evident that pro- and anti-inflammatory DCs are responsible for their respective cytokines release. However, role of DCs in vitiligo is enigmatic. In the present study, we assessed DCs markers (CD11b and CD11c) along with pro- and anti-inflammatory cytokines (IL-17A, IL-10 and IL-12p70) in stable and active vitiligo patients. Our results revealed a significant augmented expression of CD11b+CD11c+ (pro-inflammatory DC) in peripheral blood mononuclear cells (PBMCs) and skin tissues of active vitiligo patients versus control and stable vitiligo group. Unlikely, CD11b+ (anti-inflammatory DC) levels were significantly impeded in active vitiligo group as compared to another two groups. CD11c (T helper 1 stimulating DC) presented no significant alterations in any group. Furthermore, we perceived significantly up-regulated IL-17A (pro-inflammatory cytokine) and down-regulated IL-10 (anti-inflammatory cytokine) expressions in active vitiligo group as compared to control and stable group (in sera, PBMCs and skin tissue). Also, a significant positive correlation was observed between CD11b+CD11c+ and IL-17A; and CD11b+ and IL-10. Contrarily, CD11b+CD11c+ and CD11b+ were negatively correlated with IL-10 and IL-17A, respectively. In conclusion, modulation of pro- and anti-inflammatory DCs in active vitiligo patients may affect cytokines production and thereby, lead to further depigmentation of skin.

A prospective, randomized clinical study to compare the efficacy of recipient site preparation using dermabrasion, cryoblister, and dermaroller in autologous noncultured epidermal cell suspension in stable vitiligo.

Noncultured epidermal cell suspension (NCES) is a well-established surgical treatment modality for stable vitiligo. The outcome of this procedure significantly depends on the method of recipient site preparation, a critical step to achieve cosmetically acceptable repigmentation. To compare the efficacy of recipient site preparation using three methods namely, dermabrasion, cryoblister, and dermaroller followed by NCES in stable vitiligo. In this single-center, prospective, intra-patient, randomized clinical trial; 36 participants having at least three vitiligo patches in same anatomic region with minimum lesional stability of 1 year were randomized 1:1:1 for recipient site preparation using manual dermabrasion, cryoblister, and dermaroller followed by NCES. Patients were followed up at 4, 8, and 12 weeks and assessment of extent and pattern of repigmentation, color match and patient satisfaction were done. Among 36 patients, 22 (61.1%) were females; mean (SD) age was 28.33 (9.4) years. Dermabrasion and cryoblister techniques showed equal efficacy with respect to extent of repigmentation (>75% repigmentation; 55.6% vs 47.2%; P = .63) and patient satisfaction score (20.2 ± 9.6 vs 19.9 ± 7.9, P = .194). However, dermabrasion was superior to cryoblister in terms of rapidity (65% vs 32.5% at 4 weeks, P = .04) and color match (47.2% vs 19.4%, P = .004). Dermaroller had poor repigmentation outcomes compared to both dermabrasion and cryoblister. Cryoblister as a method of recipient site preparation is equally effective as manual dermabrasion in NCES for attaining good to excellent repigmentation, but with risk of hyperpigmentation. However, dermaroller is inferior to both dermabrasion and cryoblister.

Exposure of cigarette smoke condensate activates NLRP3 inflammasome in vitro and in vivo: A connotation of innate immunity and atherosclerosis.

OBJECTIVE: Smoking is known to have detrimental effects on cardiovascular system. However, the potential molecular basis of smoking-induced atherosclerosis remains unclear. NLRP3 inflammasome is implicated in perpetuation of inflammatory response in atherosclerosis. Therefore, we aimed to explore the cytotoxic effects of cigarette smoke condensate (CSC) on the activation of NLRP3 inflammasome in vitro and in vivo. METHODS: For in vitro study, the pro-atherogenic effects of CSC were evaluated in THP-1 monocytes with different dose concentrations (0.1, 1, 5, 10 and 20 µg/ml) for varied time periods (6, 12, 24 and 48 h). For in vivo study, 30 male C57BL/6J mice were employed. 6 mice were sacrificed for baseline investigations. 24 mice were randomly divided into four groups: Group-I:Control mice, Group-II:CSC model, Group-III:High-fat diet(HFD) model, and Group-IV:HFD + CSC model for 14 weeks (n = 6/group). The group-II and IV mice were injected with 720 µg CSC/20 g body weight intraperitoneally (6 days/week). RESULTS: In vitro, higher dosage of CSC (20 µg/ml) was toxic to cells as significant decline in cell viability and proliferation was observed. Furthermore, the mRNA expression of NLRP3 inflammasome and its pro-cytokine levels were significantly augmented on CSC exposure in a dose-dependent manner but impeded in time-dependent manner. In vivo, CSC and HFD independently augmented the expression of NLRP3 inflammasome (~4-10 fold-change) along with pro-cytokine levels in Group-II and III vs Group-I mice whereas, HFD + CSC treatment demonstrated synergistic effects in Group-IV. CONCLUSION: Our data suggest that CSC activates NLRP3 inflammasome in vitro and in vivo and collectively with HFD has synergistic effects in vivo that may promote atherosclerosis.

Aberrant ETS-1 signalling impedes the expression of cell adhesion molecules and matrix metalloproteinases in non-segmental vitiligo.

Cell adhesion is a complex process that involves multiple molecules on the cell surface (ie cell adhesion molecules [CAMs]), surrounding cells and extracellular matrix (ECM). Repigmentation in vitiligo is dependent on the ECM remodelling and cellular migration, primarily attributed to the transcriptional activation of matrix metalloproteinases (MMPs). In this study, we aimed to demonstrate the role of ETS-1 signalling in the regulation of MMPs and CAMs. Therefore, we studied the expression of ETS-1, MMPs (MMP-2, MMP-9) and CAMs including E-cadherin, ITGA-1 and ICAM-1 in vitiligo (both active and stable) ex vivo. Further, we compared melanocyte morphology and their adhesion towards collagen IV and laminin between control and vitiligo groups in vitro. Also, we silenced ETS-1 in melanocytes cultured from control skin and observed post-silencing effect on above-mentioned MMPs and CAMs. We perceived absent ETS-1 and significantly reduced CAMs and MMPs in vitiligo compared with normal skin. Scanning electron microscopy (SEM) revealed a translucent material surrounding individual melanocytes in stable vitiligo and controls, whereas active vitiligo melanocytes demonstrated loss of this extracellular substance. Adhesion assays revealed significantly decreased binding of cultured melanocytes to collagen IV and laminin V plates in both stable and active vitiligo. Importantly, ETS-1 silencing resulted in significantly reduced expression of CAMs and MMPs. In conclusion, absent ETS-1 expression in both stable and active non-segmental vitiligo seems to impede the expression of CAMs, apart from MMPs, probably leading to progressive depigmentation in active disease and absence of spontaneous repigmentation in stable disease.

Significant reduction in the expression of interleukins-17A, 22 and 23A, forkhead box p3 and interferon gamma delineates lichen planus pigmentosus from lichen planus.

Recent studies have noticed significant role of interleukin (IL)-17, 22, 23, Foxp3, interferon-gamma (IFN-γ) and Wnt5a in oral and cutaneous lichen planus (LP). This study was undertaken to assess whether similar expression exists in lichen planus pigmentosus (LPP). We recruited 30 patients of treatment-naïve 'LPP' (in absence of cutaneous/mucosal LP elsewhere, group 1), 10 patients having active treatment-naïve cutaneous 'LP' (group 2), 10 patients having 'post-LP' hyperpigmentation (in absence of active LP and off treatment for at least past 3 months, group 3), and 10 controls. Quantitative real-time polymerase chain reaction (qRT-PCR, peripheral blood mononuclear cells [PBMCs] and skin) and immunohistochemistry (IHC, skin) was performed. mRNA expression (in PBMCs) of IL-17A, IL-22, IL-23A, IFN-γ and Foxp3 was significantly decreased in group 1 and 3 as compared to group 2 (p < 0.05). Wnt5a expression was maximal in controls; and while there was no difference between group 1 and 2; whereas expression in group 3 was significantly lesser than group 1 and 2 (p < 0.05). qRT-PCR (skin) and IHC (skin) revealed similar results; and mRNA expression and mean fluorescence intensity of IL-17A, IL-22, IL-23A/R was significantly increased in group 2 and 3 compared to group 1 (p < 0.05). Mean fluorescence intensity and mRNA expression of IFN-γ, Foxp3 and Wnt5a were significantly increased in group 2 compared to group 1 (p < 0.05); whereas the difference between group 1 and 3 was not significant. Mean fluorescence intensity and mRNA expression of IL-17A, 1L-22 and IFN-γ showed no difference between group 2 and 3; whereas that of IL-23A/R, foxp3 and wnt5a were significantly higher in group 2 than group 3 (p < 0.05). Overall, maximal expression of IL-17A, IL-22, IL-23A, IFN-γ and Foxp3 (mRNA PBMCs) was observed in LP. Minimal expression of IL-17A, IL-22, IL-23A/R, IFN-γ and Foxp3 (mRNA skin and IHC skin) was seen in LPP patients. In contrast to LP, LPP lacks the expression of IFN-γ, Foxp3 and the cytokines representing Th17 pathway, and thus seems to have a distinct pathogenesis.

Efficacy of Transplantation of Combination of Noncultured Dermal and Epidermal Cell Suspension vs Epidermal Cell Suspension Alone in Vitiligo: A Randomized Clinical Trial.

Importance: Surgical interventions, notably noncultured epidermal suspension (NCES), are the next line of treatment in patients with vitiligo who fail to respond to medical therapy. Noncultured epidermal suspension is usually performed in patients with vitiligo with duration of clinical stability (DS) of 12 months or longer because DS is a vital parameter in determining outcome of NCES. In this pilot study, we planned to assess the efficacy of a novel combination of noncultured epidermal cell suspension and noncultured dermal cell suspension (NCES and NDCS) in patients with vitiligo with shorter DS (3-6 months). Objective: To compare the efficacy of transplantation of NCES and NDCS vs NCES alone in patients with vitiligo with DS of 3 to 6 months. Design, Setting, and Participants: A single-center randomized clinical trial including 40 patients with focal, segmental, or generalized vitiligo with DS of 3 to 6 months or more than 12 months was carried out. Based on DS, 2 groups including 20 patients each were recruited (DS in group 1, 3 to 6 months; DS in group 2, more than 12 months). Each group was further randomized into 2 subgroups, A and B. Intervention: Patients in subgroups 1A and 2A underwent NCES alone, whereas patients in subgroups 1B and 2B underwent NCES and NDCS. Main Outcomes and Measures: Extent of repigmentation, color match, and pattern of repigmentation at 24 weeks. Results: Of the 40 study participants, mean (SD) age was 24.9 (4.0) years and 24 (60%) were women; in group 1 with DS for 3 to 6 months, more than 75% repigmentation at 24 weeks was observed in all 10 patients in subgroup 1B (NCES and NDCS) compared with 3 of 10 patients in subgroup 1A (NCES) (100% vs 30%, P = .003). In group 2 (DS > 12 months), the same was observed in 6 of 10 patients in subgroup 2A and 7 of 10 patients in subgroup 2B (NCES) (60% vs 70%, P > .99). The 2 groups and subgroups did not show any significant differences with respect to color matching and pattern of repigmentation. Conclusions and Relevance: Combination of NCES and NDCS resulted in excellent response in patients with vitiligo with shorter duration of clinical stability compared with NCES alone. This combination may be used early in the course of stable vitiligo without waiting for a period of 12 months or more since last clinical activity. Trial Registration: ClinicalTrials.gov identifier: NCT03013049.

Melanocyte abnormalities and senescence in the pathogenesis of idiopathic guttate hypomelanosis.

BACKGROUND: Idiopathic guttate hypomelanosis (IGH) is a pigmentary disorder of unknown pathogenesis characterized by small discrete white macules. In the skin, epidermal melanin unit between melanocytes and keratinocytes is responsible for melanin synthesis and equal distribution of melanin pigment. OBJECTIVE: Therefore, this study was designed to check the role of melanocytes in the pathogenesis of IGH. METHODS: For this study, six IGH patients and six controls were enrolled. Melanin content was checked in the skin sections and in the cultured melanocytes. Senescence was checked in the lesional skin of IGH patients by comparing the mRNA and protein expression of senescence markers p16, hp1, and p21. RESULTS: Cultured melanocytes from the IGH patients showed morphological changes in comparison to the control melanocytes. Melanocytes from IGH patients were bigger in size with very small and retracted dendrites as compared to the control melanocytes. Melanin accumulation was more in the IGH patients as compared to the controls. Our results showed that expression of p16, p21, and hp1 was significantly higher in lesional skin of IGH patient as compared to healthy controls. CONCLUSION: This study revealed large-sized melanocytes with small and retracted dendrites in IGH patients. Accumulation of more melanin in the IGH melanocytes might be due to problem in the transfer of melanin from melanocytes to keratinocytes. Accumulation of melanin can lead to the senescence in the melanocytes of IGH patients.

Increased systemic and epidermal levels of IL-17A and IL-1ß promotes progression of non-segmental vitiligo.

BACKGROUND: Non-segmental vitiligo (NSV) results from autoimmune destruction of melanocytes. The altered levels of various cytokines have been proposed in the pathogenesis of vitiligo. However, the exact immune mechanisms have not yet been fully elucidated. OBJECTIVES: To investigate the role of epidermal and systemic cytokines in active and stable NSV patients. METHODS: Serum levels of inflammatory cytokines were checked in 42 active and 30 stable NSV patients with 30 controls. The lesional, perilesional and normal skin sections were subjected to H&E staining. The mRNA expression of inflammatory cytokines and their respective receptors were assessed by quantitative PCR in lesional skin of both active and stable NSV skin. The MITF and IL-17A were immunolocalized in lesional, perilesional and normal skin tissue. RESULTS: Significant increase in the expression of inflammatory cytokines, IL-17A, IL-1ß and TGF-ß was observed in active patients, whereas no change was observed in stable patients. A marked reduction in epidermal thickness was observed in lesional skin sections. Significant increase in IL-17A and significant decrease in microphthalmia associated transcription factor (MITF) expression was observed in lesional and perilesional skin sections. Moreover, qPCR analysis showed significant alterations in the mRNA levels of IL-17A, IL-1ß, IFN-γ, TGF-ß and their respective receptors in active and stable vitiligo patient samples. CONCLUSION: Increased levels of IL-17A and IL-1ß cytokines and decreased expression of MITF suggested a possible role of these cytokines in dysregulation of melanocytic activity in the lesional skin and hence might be responsible for the progression of active vitiligo.

Senescence in the lesional fibroblasts of non-segmental vitiligo patients.

Dermal fibroblasts secrete various growth factors which are important for skin pigmentation. Imbalance in the synchronization of epidermal and dermal cells in the skin can play vital role in the pathogenesis of pigmentary disorder vitiligo. Therefore, our objective was to check the lesional fibroblasts for any abnormality and senescence in non-segmental vitiligo patients (NSV). Skin punch biopsies were taken from NSV patients and healthy controls. Explant culture of fibroblast from lesional dermis, non-lesional dermis, and control was analyzed. The senescence was confirmed by ß-galactosidase staining in the cultured fibroblasts. Senescence was checked at mRNA level in lesional dermis, non-lesional dermis of NSV patients by senescence markers p16, p21, and hp1 by quantitative real-time polymerase chain reaction (qRT-PCR) and immunofluorescence study was used for protein analysis. Morphological results showed number of fibroblasts with bigger perinuclear region and vacuoles were more in the lesional fibroblasts. Number of ß-galactosidase positive fibroblasts in the lesional skin of NSV patients was higher as compared to the non-lesional and control fibroblasts. Results showed higher relative gene expression of senescence markers p16, p21, and hp1 in the lesional dermis of NSV patients at mRNA level and protein level as compared with control. Senescence in the dermal fibroblasts can decrease the secretion of growth factors and cytokines secreted by fibroblasts which may lead to the melanocyte death and progression of vitiligo. However, further studies on larger number of patients are needed to confirm the role of fibroblasts in the vitiligo pathogenesis.

Phosphorylated cellulose triacetate-silica composite adsorbent for recovery of heavy metal ion.

Phosphorylated cellulose triacetate (CTA)/silica composite adsorbent was prepared by acid catalyzed sol-gel method using an inorganic precursor (3-aminopropyl triethoxysilane (APTEOS)). Reported composite adsorbent showed comparatively high adsorption capacity for Ni(II) in compare with different heavy metal ions (Cu(2+), Ni(2+), Cd(2+) and Pb(2+)). For Ni(II) adsorption, effect of time, temperature, pH, adsorbent dose and adsorbate concentration were investigated; different kinetic models were also evaluated. Thermodynamic parameters such as ΔG°, ΔH° and ΔS° were also estimated and equilibrium adsorption obeyed Langmuir and Freundlich isotherms. Developed adsorbent exhibited about 78.8% Ni(II) adsorption at pH: 6 and a suitable candidate for the removal of Ni(II) ions from wastewater. Further, about 65.5% recovery of adsorbed Ni(II) using EDTA solution was demonstrated, which suggested effective recycling of the functionalized beads would enable it to be used in the treatment of contaminated water in industry.