Protective role of Withaferin-a on red blood cell integrity during 7,12-dimethylbenz[A]anthracene induced oral carcinogenesis

The aim of the present study was to investigate the protective effect of Withaferin-A on red blood cell integrity during 7,12-dimethylbenz[a]anthracene (DMBA) induced oral carcinogenesis. The protective effect of Withaferin-A was assessed by measuring the status of glycoconjugates, membrane bound enzyme activity and red blood cell osmotic fragility. Oral squamous cell carcinoma was induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin thrice a week for 14 weeks. The levels of glycoconjugates, membrane bound enzyme activity, osmotic fragility and thiobarbituric acid reactive substances (TBARS) were analyzed by using specific colorimetric methods. We observed 100% tumor formation in DMBA painted hamsters. Increase in plasma glycoconjugates at the expense of red blood cell membrane glycoconjugates levels were observed in DMBA painted hamsters as compared to control hamsters. Erythrocytes from DMBA painted hamsters were more fragile than those from control hamsters. The activity of membrane bound enzyme (Na+ K+ ATPase) decreased whereas TBARS level was increased in DMBA painted hamsters as compared to control hamsters. Oral administration of Withaferin-A at a dose of 20mg kg-1 bw significantly prevented the tumor formation as well as normalized the biochemical variables in DMBA painted hamsters. Our results thus demonstrate the protective effect of Withaferin-A on red blood cell integrity during DMBA induced oral carcinogenesis.Key words: DMBA, Withaferin-A, Oral cancer, glycoconjugates, osmotic fragility

PROTECTIVE ROLE OF WITHAFERIN-A ON RED BLOOD CELL INTEGRITY DURING 7,12-DIMETHYLBENZ[A]ANTHRACENE INDUCED ORAL CARCINOGENESIS

The aim of the present study was to investigate the protective effect of Withaferin-A on red blood cell integrity during 7,12-dimethylbenz[a]anthracene (DMBA) induced oral carcinogenesis. The protective effect of Withaferin-A was assessed by measuring the status of glycoconjugates, membrane bound enzyme activity and red blood cell osmotic fragility. Oral squamous cell carcinoma was induced in the buccal pouch of Syrian golden hamsters by painting with 0.5% DMBA in liquid paraffin thrice a week for 14 weeks. The levels of glycoconjugates, membrane bound enzyme activity, osmotic fragility and thiobarbituric acid reactive substances (TBARS) were analyzed by using specific colorimetric methods. We observed 100% tumor formation in DMBA painted hamsters. Increase in plasma glycoconjugates at the expense of red blood cell membrane glycoconjugates levels were observed in DMBA painted hamsters as compared to control hamsters. Erythrocytes from DMBA painted hamsters were more fragile than those from control hamsters. The activity of membrane bound enzyme (Na+ K+ ATPase) decreased whereas TBARS level was increased in DMBA painted hamsters as compared to control hamsters. Oral administration of Withaferin-A at a dose of 20mg kg-1 bw significantly prevented the tumor formation as well as normalized the biochemical variables in DMBA painted hamsters. Our results thus demonstrate the protective effect of Withaferin-A on red blood cell integrity during DMBA induced oral carcinogenesi

Neighbours of cancer-related proteins have key influence on pathogenesis and could increase the drug target space for anticancer therapies

Even targeted chemotherapies against solid cancers show a moderate success increasing the need to novel targeting strategies. To address this problem, we designed a systems-level approach investigating the neighbourhood of mutated or differentially expressed cancer-related proteins in four major solid cancers (colon, breast, liver and lung). Using signalling and protein–protein interaction network resources integrated with mutational and expression datasets, we analysed the properties of the direct and indirect interactors (first and second neighbours) of cancer-related proteins, not found previously related to the given cancer type. We found that first neighbours have at least as high degree, betweenness centrality and clustering coefficient as cancer-related proteins themselves, indicating a previously unknown central network position. We identified a complementary strategy for mutated and differentially expressed proteins, where the affect of differentially expressed proteins having smaller network centrality is compensated with high centrality first neighbours. These first neighbours can be considered as key, so far hidden, components in cancer rewiring, with similar importance as mutated proteins. These observations strikingly suggest targeting first neighbours as a novel strategy for disrupting cancer-specific networks. Remarkably, our survey revealed 223 marketed drugs already targeting first neighbour proteins but applied mostly outside oncology, providing a potential list for drug repurposing against solid cancers. For the very central first neighbours, whose direct targeting would cause several side effects, we suggest a cancer-mimicking strategy by targeting their interactors (second neighbours of cancer-related proteins, having a central protein affecting position, similarly to the cancer-related proteins). Hence, we propose to include first neighbours to network medicine based approaches for (but not limited to) anticancer therapies

Surgical procedures for hidradenitis suppurativa

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease that can have a considerable social and psychosocial impact in patients with skin of color. The lesions are difficult to treat and often present with notable frustration for both patients and physicians. Although current treatment ladders can delay procedures and surgical intervention, some believe that surgery should be introduced earlier in the management of HS. In this article, we review current surgical procedures for the management of HS. It is imperative that dermatologists are informed about the different techniques available for treating this disease to determine the best route to care for their patients

Patient-reported outcomes in hidradenitis suppurativa: A review

Hidradenitis suppurativa, also known as acne inversa, is a chronic recurrent inflammatory disease of the skin making management challenging and continuously evolving. A large number of modalities exist aimed at quantifying the efficacy of treatment in studies on hidradenitis suppurativa. Both physician-reported and patient-reported outcomes are used as endpoints in these studies; however, the vast majority of the modalities used to survey these reported outcomes lack validation and congruence between studies. Heterogeneity of outcome measures and lack of standardization from study to study make it difficult to design future hidradenitis suppurativa trials and to compare results. This high variability between studies further contributes to the lack of high- quality evidence available to guide clinical management decisions of this inflammatory skin disease. Therefore this review aims to assess the modalities frequently used to assess patient- reported treatment outcomes in hidradenitis suppurativa. Patient-reported outcomes in hidradenitis suppurativa include outcomes regarding symptoms and disease progression, measures of treatment satisfaction, quality of life surveys, impairment of function, pain, and patient-reported outcomes combined with physician-reported outcomes. Nearly all surveys demonstrate significant heterogeneity, lack standardization, and many are not validated or constructed specifically for the assessment of hidradenitis suppurativa. Yet patient-reported outcomes on symptoms and disease severity, treatment satisfaction, and quality of life are instrumental in evaluating hidradenitis suppurativa treatment efficacy in clinical trials. As such, standardization and validation of patient- reported outcome instruments are essential for comparability among studies and improved quality of evidence

Nutritional Status and Food Consumption Pattern in India: A Study in Disadvantaged Areas of Madhya Pradesh

Diet and diversity gets increased attention because of its impact on nutrition and health. A study was conducted in this line in Dhar and Datia districts of Madhya Pradesh, a nutritionally disadvantaged area in India. A structured interview schedule was the tool for data collection with in-built 24-hour diet recall section. A total of 240 respondents participated in this study. The study registered a slight mark of overweight and obesity in the respondent groups. It was understood that the problem of under nourishment was less with male groups than female groups in both districts. It was also revealed that majorly, the respondent groups had low level of knowledge about nutrition. A sixteen food group model (FAO) was used to evaluate DDS (Diet Diversity Score) ranging from 0 to 7. Overall Individual DDS was medium ranging from 3.9 to 4.7 (Dhar) and 5.0 to 6.4 (Datia). The actual consumption of all the food groups taken by the respondents were quantified and it was found that least consumed food groups were pulses and fruits. The study concludes that dietary diversity is poor and efforts to improve nutritional status must address the issue of nutrition education, dietary diversity and nutrition sensitive agriculture. Acknowledgement : The authors thank the financial support provided by ICAR-Indian Agricultural Research Institute, New Delhi, India, for conducting this study under the project Enhancing Nutrition Security and Gender Empowerment

The impact of sunlight on skin aging

Purpose of Review In this review, we summarize and discuss the current literature on photoaging. We focus on the molecular effects of UV radiation, and the histological and clinical features of chronically sun-exposed skin. Recent Findings The expression of numerous proteins is altered in habitually sun-exposed skin, including sirtuins and hedgehog signaling proteins. Pharmacological manipulation of the levels of these proteins can potentially downregulate the photoaging process. Summary Mitochondrial and nuclear DNA damage, reactive oxygen species (ROS) production, and altered gene expression patterns are critical components of both photoaging and chronological aging. Chronic UVA and UVB exposure result in the photoaged phenotype through distinct molecular mechanisms, with UVA being primarily ROS-mediated and UVB being DNA damage-mediated. Molecular effects result in an altered dermal and epidermal environment that manifests as the photoaged phenotype. Importantly, skin phototype and environmental influences impact individual responses to chronic UV radiation

MODIFYING EFFECTS OF METFORMIN ON CIRCADIAN PATTERN OF BLOOD GLUCOSE, LIPID PEROXIDATION AND ENZYMATIC ANTIOXIDANTS IN ALLOXAN INDUCED DIABETIC RATS

Abstract: Aim of the study was to investigate the modifying effects of metformin on circadian pattern of blood glucose, lipid peroxidation and enzymatic antioxidants in alloxan induced diabetic rats. Diabetes mellitus was induced in overnight fasted Wistar rats by single intraperitoneal injection of freshly prepared solution of alloxan monohydrate (150mg/Kg bw) in physiological saline. The blood glucose level and the status of lipid peroxidation and antioxidants were assayed using specific colorimetric methods. Blood glucose level reached a peak at 23:19 hours in diabetic rats. The day-night rhythm of lipid peroxidation and enzymatic antioxidants were also significantly altered in alloxan induced diabetic rats. Oral administration of metformin to diabetic animals at 23:19 hours restored the circadian characteristics of blood glucose, lipid peroxidation and enzymatic antioxidants to near normal pattern in alloxan induced diabetic rats. It is concluded from present study that oral administration of metformin to diabetic animals at 23:19 hours peak glucose level maintained the blood glucose homeostasis throughout the day