Matrix Metalloproteinases (MMPs) and Diabetic Foot: Pathophysiological Findings and Recent Developments in Their Inhibitors of Natural as well as Synthetic Origin

Management of diabetic foot remains a major challenge for healthcare system. Though wound healing is a multiphase process and involved multiple biomarkers that acts in stepwise manner, pathophysiology diabetic foot ulcers is still not much clear and need standardization. Matrix metalloproteinases (MMPs) are often linked with non-healing characteristic of diabetic foot ulcers. They play vital roles in various phases of healing process. Major functions are removal of damaged extracellular matrix in inflammatory phase, breakdown of capillary basement membrane prior to angiogenesis and facilitation in fibroblast migration during proliferation phase. For efficient healing, these enzymes are needed in certain amount only. Imbalance of these enzymes leads to excessive degradation which has been linked with the non-healing nature of diabetic ulcers. This chapter will shed light on the role of MMP’s in various phases of wound healing and the inhibitors of MMP’s from natural as well as synthetic origin. It would help researchers and physicians to the understand nature of diabetic foot more clearly and design of strategies for diabetic foot management

Development and optimization of nanoparticles loaded with erucin, a dietary isothiocyanate isolated from Eruca sativa: Antioxidant and antiproliferative activities in ehrlich-ascites carcinoma cell line

The study on Erucin (ER) has gained interest of nutraceutical and pharmaceutical industries because of its anti-cancer properties. Erucin is an isothiocyanate obtained from the seeds of Eruca sativa which possess certain drawbacks such as poor aqueous solubility and bioavailability. Therefore, the present study aimed at developing ER-cubosomes (CUB) by solvent evaporation technique followed by applying Central Composite Design to optimize ER loaded cubosomes. For this purpose, independent variables selected were Monoolein (MO) as lipid and Pluronic-84 (P-84) as a stabilizer whereas dependent variables were particle size, percentage of ER loading and percentage of its entrapment efficiency. The cubosomal nanocarriers exhibited particle size in the range of 26 nm, entrapment efficiency of 99.12 ± 0.04% and drug loading of 3.96 ± 0.0001%. Furthermore, to investigate the antioxidant potential, we checked the effect of ER and ER-CUB by DNA nicking assay, DDPH assay and Phosphomolybdate assay, and results showed significant improvement in antioxidant potential for ER-CUB than ER. Similarly, ER-CUB showed enhanced anticancer activity with a marked reduction in IC50 value than ER in MTT assay. These results suggested that ER-CUB produced notable escalation in antioxidant potential and enhanced anticancer activity than ER

A study on cervical cancer screening in symptomatic women using Pap smear in a tertiary care hospital in rural area of Himachal Pradesh, India

Background: Cervical cancer is the most common cause of death among women in developing countries. India has the highest age standardized incidence in South Asia at 22. An attempt was made to know the impact of cancer screening programmes in place since 1975 in India, and to do cytological screening in symptomatic women. Material and methods: 200 women in the age group of 21–65 years who attended Gynaecology Outdoor Patient Department (OPD) who consented to participate were screened by Pap smear testing. Women who were pregnant, and known or treated case of cancer cervix were excluded from the study. Pap smears were made with conventional method. Results: None of the women had Pap smear testing in their life earlier. Only 5% women knew that the tests are available that can detect cervical cancer. All the women were married and in stable marital relationship. Mean age was 38.6 years. Most of the women were parous, had poor socio-economic status and had never used tobacco in any form. Vaginal discharge was the commonest complaint followed by inter-menstrual bleeding. 56% smears were reported as NILM, 32.5% inflammatory, 1.5% had other non-specific findings. ASC-US was in 1%, LSIL in 5.5% and HSIL in 2.5% women. Overall sensitivity and specificity for detection of LSIL were 76.9% and 96.2% and those for detection of HSIL were 66.6% and 97.6%. Conclusions: Pap smear is highly sensitive and specific method in detecting pre-cancerous lesions of cervix. Community needs to be enlightened about Pap test through diffuse educational activities

Substance abuse in Children and adolescent: A Retrospective Study

Introduction: Drug addiction among children and adolescents is spreading very fast. The age of initiation of substance use is falling progressively. Aims and Methods: The aim of the study was to know about the socio demographic profile of children and adolescents diagnosed with substance dependence and to assess the pattern of drug dependence. So we conducted a retrospective study in Swami Vivekananda Drug De addiction centre at Amritsar in Punjab. The diagnosis of substance dependence was made by a consultant psychiatrist after direct interview with the patient and the relatives according to International Classification of Diseases (ICD-10). Results: The study comprised 446 children and adolescents who reported for de addiction during the study period. Majority were in the age group 16-19(95.73%), 49.5% were from urban areas and 50.5% patients were from rural areas. Out of these 36.09% were employed, 24.43% were unemployed and 39.46% were students. Our results showed more involvement of male as compared to females. As far as education status is concerned, 47.53% studied up to matric, 23.99% up to Secondary school, 12.78% up to middle, 6.95% up to primary and 5.38% were illiterate. Opioids and polysubstance use are common among them. Conclusion: The need of the hour is to educate and counsel young children and adolescents and create awareness among the public regarding drug addiction

Targeting JAK/STAT signaling pathway and anti-inflammatory markers using bakuchiol isolated from Psoralea corylifolia for cytotoxicity of human squamous cell carcinoma (A431) cells

Objectives: Non melanoma skin cancers are common neoplasms worldwide. In India, squamous cell carcinoma (SCC), is the most prevalent skin disorder and its incidence rises quickly with cumulative exposure to sun. Numerous techniques are available for SCC but reversion and metastasis are common concern that needs effective and safe strategies for its control. With this in view, the study was planned to investigate the activity of Bakuchiol (Bak), traditionally used in various countries for curing skin ailments but its mechanism of action is unexplored. In our study, we explored anti-proliferative, pro-apoptotic and anti-inflammatory potential of Bak toward human squamous carcinoma (A431) cell line. Methods: The pure compound Bak was isolated from the plant Psoralea corylifolia and characterized using NMR, HRMS and FTIR. To explore their bioefficacy, different in vitro assays were performed against A431 cell line. To have molecular insights, RT-qPCR investigation was done to analyzed the expression level of inflammatory markers (TLR 9, IFN β, IL 23, JAK 3 and STAT 3). Results: The results showed the growth inhibitory effect on A431 cells after Bak treatment in dose-dependent way. To understand mode of cell death, cells were initially analyzed under phase-contrast, fluorescence and scanning electron microscope that showed characteristics of apoptosis. Furthermore, cell cycle studies with a flow cytometer were carried out which showed increased level of ROS, reduced MMP and cells arrested at G0/G1 phase in Bak treated cells further strengthening the induction of apoptosis. Moreover, RT-qPCR analysis indicated the downregulation of inflammatory markers in Bak-treated A431 cells that further confirmed its therapeutic role. The molecular docking study also confirmed that Bak has perfect scaffold that can complete the pharmacophoric need for JAK3 kinase inhibition. Conclusion: A critical analysis of results points towards the role of Bak in ameliorating inflammatory markers along with apoptosis induction in A431 cells by regulating the expression level of variable markers

Modulation of atrazine-induced chromosomal aberrations and cyclin-dependent kinases by aqueous extract of Roylea cinerea (D.Don) Baillon leaves in Allium cepa

Abstract Roylea cinerea (D.Don) Baillon an indigenous medicinal plant of Lamiaceae family used for the treatment of several diseases. In the present study, its aqueous (leaves) extract was tested for genoprotective action against atrazine-induced chromosomal aberrations in the root tip cells of Allium cepa. Atrazine is a herbicide of triazine class commonly used to inhibit the growth of broad leaf and grassy weeds. In order to find the concentration of atrazine that exhibits maximum toxicity, its different concentrations (1, 5 and 10 µg/mL) were tested. It was observed that 10 µg/mL concentration was more toxic as it reduced the mitotic index and also increased the chromosomal aberrations. Among all the tested concentrations of aqueous (leaves) extracts (0.25. 0.5, 1.0, 1.5 and 3.0 µg/mL), the3.0 µg/mL concentration in both modes of experiments i.e. pre and post showed a significant reduction in chromosomal aberrations induced by atrazine. To understand the mechanism of protection by plant extract on atrazine-induced chromosomal abnormalities the RT-qPCR studies were conducted to observe the expression of marker genes Cyclin-dependent kinases (CDKs) (CDKA:1, CDKB2:1 and CDKD1:1. For this, the RNA was extracted from root tips treated with extract along with atrazine by TRIzol®. It was observed that aqueous extract of Roylea cinerea (D.Don) Baillon leaves upregulated the CDKs gene expression in both the modes i.e. pre and post treatments. A critical analysis of results indicated that aqueous extract ameliorated the chromosomal aberrations caused by atrazine which may be be due to the increased expression level of CDKs genes