52 research outputs found
Comparison of Healthy and Dandruff Scalp Microbiome Reveals the Role of Commensals in Scalp Health
Several scalp microbiome studies from different populations have revealed the association of dandruff with bacterial and fungal dysbiosis. However, the functional role of scalp microbiota in scalp disorders and health remains scarcely explored. Here, we examined the bacterial and fungal diversity of the scalp microbiome and their potential functional role in the healthy and dandruff scalp of 140 Indian women. Propionibacterium acnes and Staphylococcus epidermidis emerged as the core bacterial species, where the former was associated with a healthy scalp and the latter with dandruff scalp. Along with the commonly occurring Malassezia species (M. restricta and M. globosa) on the scalp, a strikingly high association of dandruff with yet uncharacterized Malassezia species was observed in the core mycobiome. Functional analysis showed that the fungal microbiome was enriched in pathways majorly implicated in cell-host adhesion in the dandruff scalp, while the bacterial microbiome showed a conspicuous enrichment of pathways related to the synthesis and metabolism of amino acids, biotin, and other B-vitamins, which are reported as essential nutrients for hair growth. A systematic measurement of scalp clinical and physiological parameters was also carried out, which showed significant correlations with the microbiome and their associated functional pathways. The results point toward a new potential role of bacterial commensals in maintaining the scalp nutrient homoeostasis and highlights an important and yet unknown role of the scalp microbiome, similar to the gut microbiome. This study, therefore, provides new perspectives on the better understanding of the pathophysiology of dandruff
Basic science232. Certolizumab pegol prevents pro-inflammatory alterations in endothelial cell function
Background: Cardiovascular disease is a major comorbidity of rheumatoid arthritis (RA) and a leading cause of death. Chronic systemic inflammation involving tumour necrosis factor alpha (TNF) could contribute to endothelial activation and atherogenesis. A number of anti-TNF therapies are in current use for the treatment of RA, including certolizumab pegol (CZP), (Cimzia ®; UCB, Belgium). Anti-TNF therapy has been associated with reduced clinical cardiovascular disease risk and ameliorated vascular function in RA patients. However, the specific effects of TNF inhibitors on endothelial cell function are largely unknown. Our aim was to investigate the mechanisms underpinning CZP effects on TNF-activated human endothelial cells. Methods: Human aortic endothelial cells (HAoECs) were cultured in vitro and exposed to a) TNF alone, b) TNF plus CZP, or c) neither agent. Microarray analysis was used to examine the transcriptional profile of cells treated for 6 hrs and quantitative polymerase chain reaction (qPCR) analysed gene expression at 1, 3, 6 and 24 hrs. NF-κB localization and IκB degradation were investigated using immunocytochemistry, high content analysis and western blotting. Flow cytometry was conducted to detect microparticle release from HAoECs. Results: Transcriptional profiling revealed that while TNF alone had strong effects on endothelial gene expression, TNF and CZP in combination produced a global gene expression pattern similar to untreated control. The two most highly up-regulated genes in response to TNF treatment were adhesion molecules E-selectin and VCAM-1 (q 0.2 compared to control; p > 0.05 compared to TNF alone). The NF-κB pathway was confirmed as a downstream target of TNF-induced HAoEC activation, via nuclear translocation of NF-κB and degradation of IκB, effects which were abolished by treatment with CZP. In addition, flow cytometry detected an increased production of endothelial microparticles in TNF-activated HAoECs, which was prevented by treatment with CZP. Conclusions: We have found at a cellular level that a clinically available TNF inhibitor, CZP reduces the expression of adhesion molecule expression, and prevents TNF-induced activation of the NF-κB pathway. Furthermore, CZP prevents the production of microparticles by activated endothelial cells. This could be central to the prevention of inflammatory environments underlying these conditions and measurement of microparticles has potential as a novel prognostic marker for future cardiovascular events in this patient group. Disclosure statement: Y.A. received a research grant from UCB. I.B. received a research grant from UCB. S.H. received a research grant from UCB. All other authors have declared no conflicts of interes
Novel class of hybrid natural products derived from Lupeol/Lupenone (Part-II)
275-283Triterpene lupeol/lupenone isolated from
plant Crataeva nurvala has been
chemically modified and prototype hybrid forms
of lupeol have been prepared
Catalysis and mechanism of malonyl transferase activity in type II fatty acid biosynthesis acyl carrier proteins
One of the unexplored, yet important aspects of the biology of acyl carrier proteins (ACPs) is the self-acylation and malonyl transferase activities dedicated to ACPs in polyketide synthesis. Our studies demonstrate the existence of malonyl transferase activity in ACPs involved in type II fatty acid biosynthesis from Plasmodium falciparum and Escherichia coli. We also show that the catalytic malonyl transferase activity is intrinsic to an individual ACP. Mutational analysis implicates an arginine/lysine in loop II and an arginine/glutamine in helix III as the catalytic residues for transferase function. The hydrogen bonding properties of these residues appears to be indispensable for the transferase reaction. Complementation of fabD(Ts) E. coli highlights the putative physiological role of this process. Our studies thus shed light on a key aspect of ACP biology and provide insights into the mechanism involved therein
Evolutionary Significance of Self-acylation Property in Acyl Carrier Proteins
Acyl carrier protein is an integral component of many cellular metabolic processes. A number of studies have reported self-acylation behavior in acyl carrier proteins. Although AM exhibit high levels of similarity in their primary and tertiary structures, self-acylation behavior is restricted to only some ACPs that can be classified into two major families based on their function. The first family of ACPs is involved in polyketide biosynthesis, whereas the second family participates in fatty acid synthesis. Facilitated by the growing number of genome sequences available for analyses, large-scale phylogenetic studies were used in these studies to uncover as to how self-acylation behavior of acyl carrier proteins is linked with the evolution of metabolic pathways in organisms. These studies show that self-acylation behavior in acyl carrier proteins was lost during the course of evolution, with certain organisms and organelles viz. plastids, retaining it for specified functions. (C) 2009 IUBMB IUBMB Life, 61(8): 853-859, 200
Recent advances on Regularized Generalized Canonical Correlation Analysis. Applications to deciphering the chronic effects of urban pollution exposure.
International audienc
Monocyte derived IL 10 and PGE<SUB>2</SUB> are associated with the absence of Th 1 cells and in vitro T cell suppression in lepromatous leprosy
Our previous studies had shown that the clinicopathological spectrum in leprosy was associated with discrete T cell subsets in circulation, with tuberculoid patients having antigen-induced Th 1, whereas lepromatous leprosy patients with antigen-specific T cell anergy possesed Th 2 cells [1]. The present study shows that infected monocytes from lepromatous but not tuberculoid leprosy patients released soluble factors (MoF(s)) containing IL-10 and PGE2 which inhibited M. leprae induced in vitro lymphoproliferation of previously sensitised healthy or tuberculoid leprosy subjects. A strong negative correlation was observed between adherant cell derived IL-10 and IL-2 at the level of both the product and cytokine mRNA. Moreover, anti-IL-10 antibodies and indomethacin partially reversed the suppressor effects of MoF(s). Taken together these studies indicate that infected monocytes contribute to the development of T cell anergy by releasing factors that affect regulatory cytokines and T cell subset differentiation in lepromatous leprosy
- …