PER2 gene and its association with sleep-related disorders: A review.

The natural circadian rhythm in an individual governs the sleep-wake cycle over 24 h. Disruptions in this internal cycle can lead to major health hazards and sleep disorders. Reports suggest that at least 50 % of people worldwide suffer from sleep-related disorders. An increase in screen time, especially in the wake of the COVID-19 pandemic, is one of the external causative factors for this condition. While many factors govern the circadian clock and its aberrance, the PER2 gene has been strongly linked to chronotypes by many researchers. The current paper provides an extensive examination of key Single Nucleotide Polymorphisms within the PER2 gene and their potential connection to four major types of sleep disorders. This study investigates whether these SNPs play a causative role in sleep disorders or if they are solely associated with these conditions. Additionally, we explore whether these genetic variations exert a lifelong influence on these sleep patterns or if external triggers contribute to the development of sleep disorders. This gene is a crucial regulator of the circadian cycle responsible for the transcription of other clock genes. It regulates a variety of physiological systems such as metabolism, sleep, body temperature, blood pressure, endocrine, immunological, cardiovascular, and renal function. We aim to establish some clarity to the multifaceted nature of this gene, which is often overlooked, and seek to establish the mechanistic role of PER2 gene mutations in sleep disorders. This will improve further understanding, assessment, and treatment of these conditions in future.

Simple formulation and characterization of double emulsion variant designed to carry three bioactive agents.

Multiple emulsions are thermodynamically stable systems that mark applications in various fields including drug delivery systems. They allow enhanced availability of drugs, greater absorption, and present reduced toxicity, among other desirable properties. In this work, we aimed to formulate a unique double emulsion (O1/W + W1/O2/W/W) with three bioactive components viz. Ocimum tenuiflorum oil, Cocos nucifera oil and crystalline Cinnamomum camphora. Three surfactants with different HLB values viz. Tween-20, Tween-80 and Triton X-100 were used for the emulsification process. The method followed was simple as compared to current methods employed for formulating multiple emulsions. Formulation was characterized using techniques of bright field microscopy, Dynamic Light Scattering (DLS), High-Resolution Transmission Electron Microscopy (HR-TEM) and Fourier-transform infrared spectroscopy (FTIR). Image processing tools were also used to characterize the formulation, which reliably cross-verified the observations from conventional characterization techniques. The potency of individual components of emulsion was compared with the prepared double emulsion model by testing the activity on two pathologically relevant bacterial strains: Fusobacterium nucleatum (FN) and Porphyromonas gingivalis (PG).

Collagen deposition correlates with loss of E-cadherin and increased p63 expression in dysplastic conditions of oral submucous fibrosis.

This paper focuses on the status of epithelial markers, E-cadherin, and p63 in the backdrop of an abnormal amount of collagen in the sub-mucosa of dysplastic and non-dysplastic grades of OSF. Histologically confirmed OSF and normal oral mucosa samples were procured. Samples were stained by Van Gieson's stain (VG) and immunohistochemistry. The captured images were analyzed by ImageJ software to quantify their grayscale intensities. There was a gradual increase in the intensity of VG stain from normal to non-dysplastic and dysplastic OSF and the differences in their mean grayscale values were found to be significant (p < 0.00001). The intensity of E-cadherin was found to be the highest in non-dysplastic conditions and lowest in dysplastic conditions. The intensity difference of E-cadherin between normal and non-dysplastic OSF was found to be significant (p < 0.00001). The grayscale scale intensity values for p63 in whole epithelium depicted significant differences between normal and diseased conditions but for its intensity, in basal cells, significant differences were found between non-dysplastic and other classes of tissues. There was a positive correlation observed between VG and p63 staining intensity. The diseased oral epithelium demonstrated greater deposition of sub-epithelial collagen fibers along with subsequent loss of E-cadherin and an increased p63 expression.

Hydrogels and Their Role in Bone Tissue Engineering: An Overview.

An increasing incidence of the bone damage either due to trauma or a wide range of diseases related to bone necessitates the advent of new technologies or modification of the existing pattern of treatment to deliver utmost care to an individual thereby helping them to lead a normal and healthy life. Revolutionary changes in the field of tissue engineering (TE) pave a way from repair to regeneration of human tissues and restoring the health of an individual. Among the numerous biomaterials available, hydrogel emerges as a promising source of scaffold material in the field of bone TE (BTE). This article presents an overview on hydrogels and their role in BTE.

Characterization of alginate-capped nanosilver by fractal and entropy analysis on its transmission electron microphotographs.

The study employs conventional techniques and quantitative image analysis tools to characterize alginate-capped nanosilver synthesized by green methods. Sodium Alginate (0.5 %, 1 % and 2 %) was used as a reducing and stabilizing agent. Presence of particles was confirmed by UV-vis Spectroscopy, with absorbance maxima of 412-413 nm for 0.5 %, 1 % and 2 % of polymer. Hydrodynamic sizes of particles recorded for 0.5 %, 1 % and 2 % polymer were 128.4 ± 1.5, 129.9 ± 3.6 and 148.6 ± 1.0 nm by DLS. TEM revealed roughly spherical to cuboidal particles ranging from 15-20 nm and clusters of 100 nm and Energy Dispersive X-ray Spectroscopy confirmed the presence of silver in the particles. Analysis of the TEM images was done in MATLAB R2016b using histogram equalisation for image enhancement and entropy filtering for image segmentation. These techniques revealed the surface pores and polymer distribution around the particle. Statistical analysis (ANOVA) was performed for the measured fractal dimensions of nanoparticles with polymer coating, width of particle together with polymer coating, and thickness of only polymer coating around the particle for various study groups. Significant differences (p < 0.05) were found both between and within the study groups for fractal dimensions of nanoparticles with polymer coating, width of nanoparticles and thickness of polymer coating alone. The analysis was successful in confirming presence and thickness of polymer layer on particles.

Epithelial Distribution of E-Cadherin, p63, and Mitotic Figures in ApoTome Images to Determine the Oncogenic Potentiality of Oral Submucous Fibrosis.

The exact process of the malignant conversion of oral submucous fibrosis (OSF) to oral cancer is not fully understood. This study aimed to detect and analyze E-cadherin expression, p63 expression, and number of mitotic figures, all correlated to cancer development, in ApoTome images of oral tissues to determine the oncogenic potentiality of OSF. ApoTome images of the study groups (6 normal, 16 OSF with dysplasia, and 10 OSF without dysplasia) were recorded. Cytoplasmic and membranous E-cadherin expression, breakages of the cell membrane, and p63 expression were detected in MATLAB 2016b. The number of mitotic figures detected by MATLAB was correlated with the number of chromosomes detected by ImageJ. A Mann­Whitney U test was done to determine a significant difference between the study groups for cytoplasmic and membranous E-cadherin distribution points. Statistical significant differences were found for cytoplasmic E-cadherin distribution between normal and OSF (with dysplasia) (p = 0.0278). There was an increase in mitotic figures, p63 expression, and cytoplasmic E-cadherin expression and a decrease in membranous E-cadherin expression from normal to diseased condition. Hence, automated detection and quantification of E-cadherin, p63, and mitotic figures in ApoTome images of oral biopsies can help in determining the oncogenic potentiality of OSF.

Treatment of glaucoma by prostaglandin agonists and beta-blockers in combination directly reduces pro-fibrotic gene expression in trabecular meshwork.

Prostaglandin analogues (PG), beta-blockers (BB) or their combination (PG+BB) are used primarily to reduce the intraocular pressure (IOP) pathologically associated with glaucoma. Since, fibrosis of the trabecular meshwork (TM) is a major aetiological factor in glaucoma, we studied the effect of these drugs on fibrosis-associated gene expression in TM of primary glaucoma patients. In the present study, TM and iris of primary open-angle (n = 32) and angle-closure (n = 37) glaucoma patients were obtained surgically during trabeculectomy and categorized based on the type of IOP-lowering medications use as PG, BB or PG+BB. mRNA expression of pro-fibrotic and anti-fibrotic genes was quantified using qPCR in these tissues. The gene expression levels of pro-fibrotic genes were significantly lower in PG+BB as compared to other groups. These observations and underlying signalling validated in vitro in human TM cells also showed reduced fibrotic gene and protein expression levels following PG+BB treatment. In conclusion, it is observed that PG+BB combination rather than their lone use renders a reduced fibrotic status in TM. This further suggests that IOP-lowering medications, in combination, would also modulate fibrosis-associated molecular changes in the TM, which may be beneficial for maintaining aqueous out-flow mechanisms over the clinical treatment duration.

Therapeutic potential of mesenchymal stem cells in treating both types of diabetes mellitus and associated diseases.

Diabetes mellitus is a common lifestyle disease which can be classified into type 1 diabetes mellitus and type 2 diabetes mellitus. While both result in hyperglycemia due to lack of insulin action and further associated chronic ailments, there is a marked distinction in the cause for each type due to which both require a different prophylaxis. As observed, type 1 diabetes is caused due to the autoimmune action of the body resulting in the destruction of pancreatic islet cells. On the other hand, type 2 diabetes is caused either due to insulin resistance of target cells or lack of insulin production as per physiological requirements. Attempts to cure the disease have been made by bringing drastic changes in the patients' lifestyle; parenteral administration of insulin; prescription of drugs such as biguanides, meglitinides, and amylin; pancreatic transplantation; and immunotherapy. While these attempts cause a certain degree of relief to the patient, none of these can cure diabetes mellitus. However, a new treatment strategy led by the discovery of mesenchymal stem cells and their unique immunomodulatory and multipotent properties has inspired therapies to treat diabetes by essentially reversing the conditions causing the disease. The current review aims to enumerate the role of various mesenchymal stem cells and the different approaches to treat both types of diabetes and its associated diseases as well.

Synthesis of ZnO/Fe3O4/rGO nanocomposites and evaluation of antibacterial activities towards E. coli and S. aureus.

Antibacterial activity of nanoparticles (NPs) and nanocomposites (NCs) has received wide spread attention in biomedical applications. In this direction, the authors prepared zinc oxide (ZnO), iron oxide (Fe3O4), and their composite including reduced graphene oxide (rGO) by hydrothermal method. The structural and microstructural properties of the synthesised NPs and NCs were investigated by XRD, FT-IR, UV-Vis, TGA, and TEM analysis. PEG-coated ZnO and Fe3O4 form in hexagonal wurtzite and inverse spinel structures, respectively. ZnO forms in rod-shaped (aspect ratio of ∼3) morphology, whereas well-dispersed spherical-shaped morphology of ∼10 nm is observed in Fe3O4 NPs. The ZnO/Fe3O4 composite possesses a homogeneous distribution of above two phases and shows a very good colloidal stability in aqueous solvent. These synthesised particles exhibited varying antibacterial activity against gram-positive strain Staphylococcus aureus (S. aureus) and gram-negative strain Escherichia coli (E. coli). The nanocomposite exhibits a better cidal effect on E. coli when compared to S. aureus when treated with 1 mg/ml concentration. Further, the addition of rGO has intensified the anti-bacterial effect to a much higher extent due to synergistic influence of individual components.

Amelioration of excision wounds by topical application of green synthesized, formulated silver and gold nanoparticles in albino Wistar rats.

Wound healing, a complex biological process, has attained a lot of attention as dermatologists are primarily interested in stimulated wound closure without formation of scar or a faint scar. The recent upsurgence of nanotechnology has provided novel therapeutic materials in the form of silver and gold nanoparticles which accelerate the wound healing process. The effect of formulated nanoparticles using Coleus forskohlii root extract (green synthesized) has been tried out for ameliorating full thickness excision wounds in albino Wistar male rats. The evaluation of in vivo activity of nanoparticles in wound healing was carried out on open wounds made by excision on the dorsal sides of albino Wistar rats under anesthesia, and the healing of the wounds was assessed. Histological aspects of the healing process were studied by a HE (Hematoxylin and Eosin) staining method to assess various degrees of re-epithelialization and the linear alignment of the granulation tissue whereas Van Gieson's histochemical staining was performed to observe collagen fibers. The healing action shown by the formulated nanoparticles was remarkable during the early stages of wound healing, which resulted in the substantial reduction of the whole healing period. Topical application of formulated gold nanoparticles was found to be more effective in suppressing inflammation and stimulating re-epithelialization compared to silver nanoparticles during the healing process. The results throw light on the amelioration of excision wounds using nanoparticles which could be a novel therapeutic way of improving wound healing in clinical practice. The mechanism of advanced healing action of both types of nanoparticles could be due to their antimicrobial, antioxidant and anti-inflammatory properties.

Computer-aided molecular pathology interpretation in exploring prospective markers for oral submucous fibrosis progression.

BACKGROUND: Evaluation of molecular pathology markers using a computer-aided quantitative assessment framework would help to assess the altered states of cellular proliferation, hypoxia, and neoangiogenesis in oral submucous fibrosis and could improve diagnostic interpretation in gauging its malignant potentiality. METHODS: Immunohistochemical (IHC) expression of c-Myc, hypoxia-inducible factor-1-alpha (HIF-1α), vascular endothelial growth factor (VEGF), VEGFRII, and CD105 were evaluated in 58 biopsies of oral submucous fibrosis using computer-aided quantification. After digital stain separation of original chromogenic IHC images, quantification of the diaminobenzidine (DAB) reaction pattern was performed based on intensity and extent of cytoplasmic, nuclear, and stromal expression. RESULTS: Assessment of molecular expression proposed that c-Myc and HIF-1α may be used as strong screening markers, VEGF for risk-stratification and VEGFRII and CD105 for prognosis of precancer into oral cancer. CONCLUSION: Our analysis indicated that the proposed method can help in establishing IHC as an effective quantitative immunoassay for molecular pathology and alleviate diagnostic ambiguities in the clinical decision process.

Connecting cyto-nano-architectural attributes and epithelial molecular expression in oral submucous fibrosis progression to cancer.

OBJECTIVE: Problems in pre-cancer diagnosis complicate cancer theragnosis as well as life expectancy. There is uncertainty regarding malignant transformation of oral submucous fibrosis (OSF), an oral pre-cancer with dysplastic (OSFWD) and non-dysplastic (OSFWT) subtypes. Understanding the structural, molecular and physical aspects of epithelial homeostasis may be useful. MATERIALS AND METHODS: Histopathological grading of biopsy sections was performed using H&E staining. Alterations in epithelial surface architecture in different groups was evaluated using scanning electron microscopy (SEM). The expression of crucial epithelial genes (p63, CK-5/6, CK-10, E-cadherin and ß-catenin) was studied by immunohistochemistry, Western blot and RT-PCR analysis. RESULTS: SEM observations revealed that the surface epithelial ridge pattern became thick and dense, and pit pattern gradually decreased in OSFWD and oral squamous cell carcinoma (OSCC). p63, ΔNp63 and CK-5/6 were up-regulated in OSFWD and OSCC but down-regulated in OSFWT. CK-10 was down-regulated in OSFWD compared to OSFWT. Cytoplasmic expression of E-cadherin and ß-catenin was elevated in dysplastic and cancerous conditions. Moreover, statistical correlation between SEM features (ridges and pits) and molecular attributes demonstrated a significant positive relationship between the ridge-to-pit ratio and p63 population density (r=0.85) and the ridge-to-pit ratio and CK-5/6 intensity (r=0.63). CONCLUSIONS: Molecular changes related to epithelial progressive maturation and cellular proliferation are correlated with concomitant alteration of epithelial surface architecture which helps to predict the malignant potentiality of OSF.

Correlated analysis of semi-quantitative immunohistochemical features of E-cadherin, VEGF and CD105 in assessing malignant potentiality of oral submucous fibrosis.

Oral submucous fibrosis, a potentially premalignant condition for oral squamous cell carcinoma, manifests both non-dysplastic and dysplastic grades. Early and specific identification of its malignant potentiality suffers from diagnostic limitations that may be addressed by correlated molecular pathology attributes having histopathological backdrop. Present study correlates expressional alteration in prime epithelial marker E-cadherin, with neo-angiogenic molecules viz. VEGF and CD105 for elucidation of malignant potentiality in different stages of oral submucous fibrosis. Sixty-eight incision biopsies from normal oral mucosa (n = 10), non-dysplastic (n = 18) and different dysplastic grades (n = 40) of oral submucous fibrosis were semi-quantitatively analyzed for immunohistochemical expressions of E-cadherin (membranous and cytoplasmic), VEGF and CD105 which were further statistically correlated. The loss of membranous E-cadherin with increase in cytoplasmic accumulation in differentiative layers of epithelium through the progression of dysplasia was noted along with up-regulation in VEGF expressions. The number of CD105(+) blood vessels and their major axis also showed significant increase from non-dysplasia toward higher grades of dysplasia. The positive correlation between deregulated expression of epithelial cell-cell adhesion molecule and increase in neo-angiogenic attributes of oral submucous fibrosis with increase in dysplastic grades indicated elucidatory potential of molecular expression features in assessment of malignant potentiality in oral submucous fibrosis.

Epithelio-mesenchymal transitional attributes in oral sub-mucous fibrosis.

Evaluating molecular attributes in association with its epithelial and sub-epithelial changes of oral sub-mucous fibrosis is meaningful in exploring the plausibility of an epithelio-mesenchymal transition (EMT) and malignant potentiality of this pathosis. In this study histopathological and histochemical attributes for basement membrane and connective tissue in biopsies of oral sub-mucous fibrosis (n = 55) and normal oral mucosa (n = 16) were assessed and expressions of p63, E-cadherin, ß-catenin, N-cadherin and TWIST were analyzed immunohistochemically. The p63 and its isoforms (TA and ∆N), PARD3, E-cadherin and ß-catenin were also assessed transcriptomically by q-PCR and EMT players like TWIST1, ZEB1, MMP9 and micro-RNA 205 were searched in gene expression microarrays. Oral epithelium demonstrating impairment in progressive maturation in oral sub-mucous fibrosis concomitantly experienced an increase in basement membrane thickness and collagen deposition along with alteration in target molecular expressions. In comparison to non-dysplastic conditions dysplastic stages exhibited significant increase in p63 and p63∆N expressions whereas, E-cadherin and ß-catenin exhibited loss from the membrane with concurrent increase in cytoplasm. Further the N-cadherin and TWIST were gained remarkably along with the appearance of nuclear accumulation features of ß-catenin. The microarray search had noticed the up-regulation of TWIST1, ZEB1 and MMP9 along with down regulation of micro-RNA 205. The simultaneous increase in basement membrane thickness and sub-epithelial collagen deposition were the plausible indicators for increased matrix stiffness with expected impact on oral epithelial functional homoeostasis. This was corroborated with the increase in expressions of epithelial master regulator p63 and its oncogenic isoform (∆N) along with membranous loss of E-cadherin (EMT hallmark) and its associate ß-catein and gain of mesenchymal markers like N-cadherin and TWIST. These also became indicative for the induction of epithelial to mesenchymal transitional mechanism in oral sub-mucous fibrosis when connoted here with the relevant modulation in expressions of EMT regulators.

Assessment of molecular events during in vitro re-epithelialization under honey-alginate matrix ambience.

Re-epithelialization is one of the most important stages of cutaneous regeneration and its success requires supportive micro-ambience which may be provided with suitable bio-matrix. Biocompatibility and efficacy of such bio-matrix in re-epithelialization could be explored by multimodal analysis of structural and functional attributes of in vitro wound healing model including evaluation of prime molecular expressions of the epithelial cells during repair. Present study examines the influence of honey-alginate and alginate matrices on re-epithelialization in keratinocyte (HaCaT) population in a 2-D wound model. Cellular viability, proliferation and cell-cell adhesion status were assessed during wound closure using live/dead cell assay and by evaluating expressions of Ki67, p63 and E-cadherin along-with % change in cellular electrical impedance. Efficacy of honey-alginate matrix in comparison to only alginate one was demonstrated by a quicker reduction in wound gap, improved cellular viability, enhanced expressions of Ki67, p63 and its isoforms (TAp63, ΔNp63) as well as E-cadherin. Faster restoration of electrical attribute (% of impedance change) after wounding also indicated better impact of honey-alginate matrix in re-epithelialization.

Finding an optimum immuno-histochemical feature set to distinguish benign phyllodes from fibroadenoma.

PURPOSE: Benign phyllodes and fibroadenoma are two well-known breast tumors with remarkable diagnostic ambiguity. The present study is aimed at determining an optimum set of immuno-histochemical features to distinguish them by analyzing important observations on expressions of important genes in fibro-glandular tissue. METHODS: Immuno-histochemically, the expressions of p63 and α-SMA in myoepithelial cells and collagen I, III and CD105 in stroma of tumors and their normal counterpart were studied. Semi-quantified features were analyzed primarily by ANOVA and ranked through F-scores for understanding relative importance of group of features in discriminating three classes followed by reduction in F-score arranged feature space dimension and application of inter-class Bhattacharyya distances to distinguish tumors with an optimum set of features. RESULTS: Among thirteen studied features except one all differed significantly in three study classes. F-Ranking of features revealed highest discriminative potential of collagen III (initial region). F-Score arranged feature space dimension and application of Bhattacharyya distance gave rise to a feature set of lower dimension which can discriminate benign phyllodes and fibroadenoma effectively. CONCLUSIONS: The work definitely separated normal breast, fibroadenoma and benign phyllodes, through an optimal set of immuno-histochemical features which are not only useful to address diagnostic ambiguity of the tumors but also to spell about malignant potentiality.

Computational analysis of p63(+) nuclei distribution pattern by graph theoretic approach in an oral pre-cancer (sub-mucous fibrosis).

BACKGROUND: Oral submucous fibrosis (OSF) is a pre-cancerous condition with features of chronic, inflammatory and progressive sub-epithelial fibrotic disorder of the buccal mucosa. In this study, malignant potentiality of OSF has been assessed by quantification of immunohistochemical expression of epithelial prime regulator-p63 molecule in correlation to its malignant (oral squamous cell carcinoma [OSCC] and normal counterpart [normal oral mucosa [NOM]). Attributes of spatial extent and distribution of p63(+) expression in the epithelium have been investigated. Further, a correlated assessment of histopathological attributes inferred from H&E staining and their mathematical counterparts (molecular pathology of p63) have been proposed. The suggested analytical framework envisaged standardization of the immunohistochemistry evaluation procedure for the molecular marker, using computer-aided image analysis, toward enhancing its prognostic value. SUBJECTS AND METHODS: In histopathologically confirmed OSF, OSCC and NOM tissue sections, p63(+) nuclei were localized and segmented by identifying regional maxima in plateau-like intensity spatial profiles of nuclei. The clustered nuclei were localized and segmented by identifying concave points in the morphometry and by marker-controlled watersheds. Voronoi tessellations were constructed around nuclei centroids and mean values of spatial-relation metrics such as tessellation area, tessellation perimeter, roundness factor and disorder of the area were extracted. Morphology and extent of expression are characterized by area, diameter, perimeter, compactness, eccentricity and density, fraction of p63(+) expression and expression distance of p63(+) nuclei. RESULTS: Correlative framework between histopathological features characterizing malignant potentiality and their quantitative p63 counterparts was developed. Statistical analyses of mathematical trends were evaluated between different biologically relevant combinations: (i) NOM to oral submucous fibrosis without dysplasia (OSFWT) (ii) NOM to oral submucous fibrosis with dysplasia (OSFWD) (iii) OSFWT-OSFWD (iv) OSFWD-OSCC. Significant histopathogical correlates and their corroborative mathematical features, inferred from p63 staining, were also investigated into. CONCLUSION: Quantitative assessment and correlative analysis identified mathematical features related to hyperplasia, cellular stratification, differentiation and maturation, shape and size, nuclear crowding and nucleocytoplasmic ratio. It is envisaged that this approach for analyzing the p63 expression and its distribution pattern may help to establish it as a quantitative bio-marker to predict the malignant potentiality and progression. The proposed work would be a value addition to the gold standard by incorporating an observer-independent framework for the associated molecular pathology.

ApoTome to visualize E-cadherin and p63 expression in oral pre-cancer.

Precise histopathological localization of E-cadherin and p63 is of immense importance in understanding the integrity of oral mucosal stratified epithelium in normal and diseased conditions. Necessarily immunohistochemical imaging should have minimum bleaching impact on the dyes and ability to produce clear and crisp images. Here ApoTome provides an alternative with metal halide light source and structured illumination under the assistance of grids, along with integrated image processing modality to generate crisp images with digital interface. The current study demonstrates the applicability of such microscopic system in capturing fluorescence images of immunohistochemical sections of normal and precancerous biopsies in respect to the expression of p63 and E-cadherin in the epithelial cells. The ApoTome images localize the nuclear and membranous expressions of p63 and E-cadherin, respectively, with remarkable specificity. The findings on E-cadherin expression have enormous diagnostic significance as these images clearly differentiate the early and advanced stages of oral submucous fibrosis based on their cytoplasmic and membranous location. Thus, this study clearly depicts a remarkable performance of ApoTome with diagnostic significance.

Optical, spectroscopic, and Doppler evaluation of "normal" and "abnormal" reflexology areas in lumbar vertebral pathology: a case study.

Scientific validation of reflexology requires an in-depth and noninvasive evaluation of "reflexology/reflex areas" in health and disease. The present paper reports the differential properties of "normal" and "abnormal" reflexology areas related to the lumbar vertebrae in a subject suffering from low back pain. The pathology is supported by radiological evidence. The reflexology target regions were clinically assessed with respect to colour and tenderness in response to finger pressure. Grey scale luminosity and pain intensity, as assessed by visual analogue scale scores, differentiated "normal" from "abnormal" skin. Skin swept source-optical coherence tomography recorded their structural differences. Infrared thermography revealed temperature variations. A laser Doppler study using a combined microcirculation and transcutaneous oxygen monitoring system indicated alterations in blood flow and oxygen perfusion. Raman spectroscopy showed differences in chemical signatures between these areas. The present findings may indicate a potential correlation between the reflexology areas and subsurface pathological changes, showing an association with the healthy or unhealthy status of the lumbar vertebrae.

Immunohistochemical Evaluation of p63, E-Cadherin, Collagen I and III Expression in Lower Limb Wound Healing under Honey.

Honey is recognized traditionally for its medicinal properties and also appreciated as a topical healing agent for infected and noninfected wounds. This study evaluates impact of honey-based occlusive dressing on nonhealing (nonresponding to conventional antibiotics) traumatic lower limb wounds (n = 34) through clinicopathological and immunohistochemical (e.g., expression of p63, E-cadherin, and Collagen I and III) evaluations to enrich the scientific validation. Clinical findings noted the nonadherence of honey dressing with remarkable chemical debridement and healing progression within 11-15 days of postintervention. Histopathologically, in comparison to preintervention biopsies, the postintervention tissues of wound peripheries demonstrated gradual normalization of epithelial and connective tissue features with significant changes in p63(+) epithelial cell population, reappearance of membranous E-cadherin (P < .0001), and optimum deposition of collagen I and III (P < .0001). Thus, the present study for the first time reports the impact of honey on vital protein expressions in epithelial and connective tissues during repair of nonhealing lower limb wounds.