A BIO-ELECTRICAL MODEL FOR PHYSIOLOGICAL EVALUATION OF NADI PARIKSHA (AYURVEDIC PULSE DIAGNOSIS)

Physiology of the traditional Ayurvedic diagnostic technique of Nadipariksha has always been a matter of controversy. This diagnostic skill is based on a fine tactile sensitivity of the physician to distinguish varied intensities of mechanical vibrations elicited by radial artery pulsation, normally perceived as Pulse Pattern Variability (PPV). Ancient exponents of Yoga and Ayurveda define Nadi as the channel of Prana which is known as the very basis of bio-energy dynamics of the body. To the modern physician Nadipariksha indicates an assessment of cardiac function which is an important aspect of vascular physiology. The above concept has been re-examined in this article, in the light of whole body bio-electrical activity pattern. The study suggests Nadi as the Energy Pulsating Pathway (EPP) encompassing cells Pulsating Bio-Electrical Response (PBER). The observed varying intensities of PPV in Nadipariksha are proposed to be due to collision of weak threshold PBER with the mechanical vibration of pulsating radial artery. The underlying mechanism of Nadipariksha has been proposed to be associated with energy dynamics of bio-electrical waveform activity at the cellular level. This approach points at its possible implications in developing a more objective diagnostic method in assessing psycho-physiological abnormalities of a patient without having to depend on the subjective diagnostic judgment of a physician. Further, this study hints at the possible experimental evidence towards a physiological evaluation of Nadipariksha through the measures of bio-impedance, bio-reactance and bio-phase angle

Oxidative damage control in a human (mini-) organ: Nrf2 activation protects against oxidative stress-induced hair growth inhibition

The in situ control of redox insult in human organs is of major clinical relevance, yet remains incompletely understood. Activation of Nrf2, the “master regulator” of genes controlling cellular redox homeostasis, is advocated as a therapeutic strategy for diseases with severely impaired redox balance. It remains to be shown whether this strategy is effective in human organs, rather than isolated human cell types. We have therefore explored the role of Nrf2 in a uniquely accessible human (mini-) organ, human scalp hair follicles (HFs). Microarray and qPCR analysis of human HFs following Nrf2 activation using sulforaphane identified the modulation of phase II metabolism, ROS clearance, the pentose phosphate pathway and glutathione homeostasis. Nrf2 knockdown (siRNA) in cultured human HFs confirmed the regulation of key Nrf2 target genes (i.e. HO-1, NQO1, GSR, GCLC, ABCC1, PRDX1). Importantly, Nrf2 activation significantly reduced ROS levels and associated lipid peroxidation. Nrf2 pre-activation reduced oxidative stress-stimulated (H2O2 or menadione) premature catagen and hair growth inhibition, significantly ameliorated the H2O2-dependent increase in matrix keratinocyte apoptosis and reversed the ROS-induced reduction in proliferation. This study thus provides direct evidence for the crucial role of Nrf2 in protecting human organ function (i.e. scalp HFs) against redox insult

Identification and analysis of novel and known genes in the rat circadian clock : the suprachiasmatic nucleus

EThOS - Electronic Theses Online ServiceGBUnited Kingdo

Mapping the expression of epithelial hair follicle stem cell-related transcription factors LHX2 and SOX9 in the human hair follicle

In the murine hair follicle (HF), the transcription factors LHX2 and SOX9 are implicated in epithelial hair follicle stem cell (eHFSC) self-renewal and the maintenance of eHFSC niche characteristics. However, the exact expression patterns of LHX2 and SOX9 in the human HF are unclear. Therefore, we have quantitatively mapped the localisation of known human eHFSC markers keratin 15 (K15) and keratin 19 (K19) in the outer root sheath (ORS) of male occipital scalp anagen HFs and related this to the localisation of LHX2 and SOX9 protein expression. As expected, K15(+) and K19(+) cells represented two distinct progenitor cell populations in the bulge and in the proximal bulb ORS (pbORS). Interestingly, cell fluorescence for K19 was significantly stronger within the pbORS versus the bulge, and vice versa for K15, describing a hitherto unrecognised differential expression pattern. LHX2 and SOX9 expressing cells were distributed throughout the ORS, including the bulge, but were not restricted to it. SOX9 expression was most prominent in the ORS immediately below the human bulge, whereas LHX2(+) cells were similarly distributed between the sub-bulge and pbORS, that is compartments not enriched with quiescent eHFSCs. During catagen development, the intensity of LHX2 and SOX9 protein expression increased in the proximal HF epithelium. Double immunostaining showed that the majority of SOX9(+) cells in the human anagen HF epithelium did not co-express K15, K19 or LHX2. This expression profile suggests that LHX2 and SOX9 highlight distinct epithelial progenitor cell populations, in addition to K15(+) or K19(+) cells, that could play an important role in the maintenance of the human HF epithelium

Divergent proliferation patterns of distinct human hair follicle epithelial progenitor niches in situ and their differential responsiveness to prostaglandin D2

Abstract Human scalp hair follicles (hHF) harbour several epithelial stem (eHFSC) and progenitor cell sub-populations organised into spatially distinct niches. However, the constitutive cell cycle activity of these niches remains to be characterized in situ. Therefore, the current study has studied these characteristics of keratin 15+ (K15), CD200+ or CD34+ cells within anagen VI hHFs by immunohistomorphometry, using Ki-67 and 5-ethynyl-2′-deoxyuridine (EdU). We quantitatively demonstrate in situ the relative cell cycle inactivity of the CD200+/K15+ bulge compared to other non-bulge CD34+ and K15+ progenitor compartments and found that in each recognized eHFSC/progenitor niche, proliferation associates negatively with eHFSC-marker expression. Furthermore, we also show how prostaglandin D2 (PGD2), which is upregulated in balding scalp, differentially impacts on the proliferation of distinct eHFSC populations. Namely, 24 h organ-cultured hHFs treated with PGD2 displayed reduced Ki-67 expression and EdU incorporation in bulge resident K15+ cells, but not in supra/proximal bulb outer root sheath K15+ progenitors. This study emphasises clear differences between the cell cycle behaviour of spatially distinct stem/progenitor cell niches in the hHF, and demonstrates a possible link between PGD2 and perturbed proliferation dynamics in epithelial stem cells

Dandruff lesional scalp skin exhibits epidermal T cell infiltration and a weakened hair follicle immune privilege

Dandruff is characterised by the presence of perivascular leukocytes and mild inflammation; however, the immune microenvironment of dandruff-affected scalp skin and the potential changes to the hair follicle's (HF) physiological immune privilege (HF IP) remain unknown. Here, we characterised the HF immune microenvironment and immune privilege status in dandruff-affected scalp skin. We assessed relevant key parameters in healthy versus dandruff-affected human scalp biopsies using quantitative immunohistomorphometry, laser capture microdissection, and RNA sequencing. The number of epidermal CD4 and CD8 T cells was increased in lesional dandruff scalp skin, while the number of MHC class II /CD1a Langerhans cells was decreased in the infundibulum. The number of intrafollicular and perifollicular CD4 T cells and CD8 T cells, perifollicular CD68 macrophages, and tryptase mast cells remained unchanged. Interestingly, MHC class Ia and ß2-microglobulin protein expression were significantly increased specifically in the suprabulbar outer root sheath (ORS) compartment of dandruff-associated HFs. RNAseq analysis of laser capture micro-dissected suprabulbar ORS compartment revealed antigen presentation pathway as the top regulated canonical pathway, along with the upregulation of HF-IP genes such as HLA-C, HLA-DP, and TAP1, which are normally down-regulated in healthy HFs. Intrafollicular protein expression of known HF IP guardians (CD200 and α-MSH) and 'danger signals' (MICA and CXCL10) remained unaltered at the IP sites of dandruff lesional HFs compared to non-lesional and healthy HFs. Instead, the expression of macrophage migration inhibiting factor (MIF), another HF IP guardian, was reduced. Together, this work shows that dandruff is associated with epidermal T-cell infiltration and a weakened HF IP in the suprabulbar ORS of HFs in dandruff lesional scalp