Aditi Jain

Nanomaterials in food and agriculture: An overview on their safety concerns and regulatory issues

ABSTRACT Nanotechnology has seen exponential growth in last decade due to its unique physicochemical properties; however, the risk associated with this emerging technology has withdrawn ample attention in the past decade. Nanotoxicity is majorly contributed to the small size and large surface area of nanomaterials, which allow easy dispersion and invasion of anatomical barriers in human body. Unique physio-chemical properties of nanoparticles make the investigation of their toxic consequences intricate and challenging. This makes it important to have an in-depth knowledge of different mechanisms involved in nanomaterialss action and toxicity. Nano-toxicity has various effects on human health and diseases as they can easily enter into the humans via different routes, mainly respiratory, dermal, and gastrointestinal routes. This also limits the use of nanomaterials as therapeutic and diagnostic tools. This review focuses on the nanomaterial–cell interactions leading to toxicological responses. Different mechanisms involved in nanoparticle-mediated toxicity with the main focus on oxidative stress, genotoxic, and carcinogenic potential has also been discussed. Different methods and techniques used for the characterization of nanomaterials in food and other biological matrices have also been discussed in detail. Nano-toxicity on different organs—with the major focus on the cardiac and respiratory system—have been discussed. Conclusively, the risk management of nanotoxicity is also summarized. This review provides a better understanding of the current scenario of the nanotoxicology, disease progression due to nanomaterials, and their use in the food industry and medical therapeutics. Briefly, the required rules, regulations, and the need of policy makers has been discussed critically.

Tea and human health: the dark shadows.

Tea is one of the most popularly consumed beverage. Depending on the manufacturing process, different varieties of tea can be produced. The antioxidative and antimutagenic potential of tea in cardiovascular diseases, cancer and obesity have long been studied. These therapeutic and nutritional benefits of tea can be attributed to the presence of flavanoids. However, these flavanoids also have certain detrimental effects on human health when their consumption exceeds certain limits. The toxicity of these flavanoids can be attributed to the formation of reactive oxygen species in the body which causes damage to the DNA, lipid membranes etc. The aim of this review is to summarize briefly, the less studied evidences of various forms of toxicity associated with tea and its harmful effects on human health.

An assessment of norepinephrine mediated hypertrophy to apoptosis transition in cardiac cells: A signal for cell death

OBJECTIVES Heart is an organ which is under a constant work load that generates numerous stress responses. Heart failure is associated with increased plasma norepinephrine (NE) and hypertrophic cell death. Within the current study we try to understand the concentration dependent molecular switch from hypertrophy to apoptosis under stress. METHODS The effect of increasing concentration of NE on cell death was studied using MTT assay based on which further experimental conditions were decided. Trypan Blue staining and TUNEL assay were done at selected concentrations of NE. Cellular and nuclear morphology at these concentrations was studied using Haematoxylin-Eosin, DAPI and PI stains. The molecular switch between hypertrophy and cell death was studied by expression analysis of β-MyHC and TNF-α. Rhodamine and DCFH-DA staining were done to evaluate the role of mitochondria and ROS under these conditions. Role of caspases under these transitions was also evaluated. RESULT NE shows steep falls in cell viability at 50 μM and 100 μM concentrations. The cellular and nuclear morphology is altered at these concentrations along with alterations at molecular level showing a shift from hypertrophy towards cell death. Altered mitochondrial membrane potential and increase in ROS support this which leads to caspase dependent activation of cell death. CONCLUSION We show that at 50 μM NE, there occurs a transition from cellular hypertrophy towards death. This could be beneficial to prevent hypertrophy induced cardiac cell death and evaluating cardio protective therapeutic targets in vitro.

MicroRNA-mediated MMP Regulation: Current Diagnostic and Therapeutic Strategies for Metabolic Syndrome

INTRODUCTION Metabolic Syndrome (MS) is a global socioeconomic problem rapidly progressing in accordance with increasing Body Mass Index (BMI) and age. It is a consortium of risk factors, such as dyslipidaemia, insulin resistance, leptin resistance, reduced adiponectin, glucose intolerance, hyperglycemia, and hypertension. Collectively, these factors accelerate the onset of type 2 diabetes mellitus, cardiovascular disease, stroke, and certain cancers such as breast, liver pancreatic, and colon cancer. Extracellular Matrix (ECM) and basement membrane remodeling play a central role during pathogenesis of MS as they regulate diverse cell functions including proliferation, differentiation, and migration. Therefore, regulation of proteins that remodel the ECM offers promising therapeutic opportunities for most of the MS. Matrix Metalloproteinases (MMPs), a family of zinc dependent endopeptidases, are the main enzymes involved in ECM remodeling. Emerging studies have reported altered levels of MMPs and the Tissue Inhibitors of Metalloproteinases (TIMPs) during MS. A number of pharmaceutical MMP inhibitors are being developed, but they have yet to be recognized for clinical applications. CONCLUSION Recently, microRNAs (~21-23-nucleotide, small non-coding, endogenous, single-stranded RNAs) have emerged as a class of promising entities for therapeutic intervention due to their ability to manipulate gene expression. The combined strategy of targeting ECM remodeling through regulation of MMPs by small non-coding RNA has produced encouraging results in pre-clinical studies for cancer and cardiovascular diseases. This review serves to provide insight into the role of microRNAs as modulators of MS and their potential as therapeutics tool through direct and indirect interactions with the MMPs.

Assessment of herb-drug synergy to combat doxorubicin induced cardiotoxicity

Aim: Doxorubicin (Dox) is one of the most cardiotoxic anti‐cancerous drug that is widely used for broad‐range of cancers. There is an urgent need for developing cardio‐oncological therapeutic interventions. Natural products having both anti‐cancerous potential as well as cardioprotective effects may hold a great potential in this regard. Curcuma longa (an Indian herb) polyphenols including curcumin, and well known for its anti‐oxidative and anti‐cancerous potential was used in the present study for its synergistic effect on cancer cells and cardiomyocytes. Material and methods: Preliminary dose dependent analysis for cell viability was conducted by MTT and trypan blue assays where the effects of curcumin and Dox on cancer cell progression and cardiotoxicity were studied. Microscopic studies were done to analyse the morphological alterations of cells followed by intracellular ROS production studies by NBT and DCFH‐DA assays. Apoptotic cellular death was studied by caspase activity and Annexin/PI FACS analysis. TUNEL assay was done followed by expression analysis of different cellular death biomarkers by quantitative real‐time PCR. Key findings: We observed that dose dependent cardiotoxicity of Dox can be significantly minimized by supplementing it with curcumin. Curcumin supplementation exaggerates oxidative stress and apoptosis leading to cancer cell death by modulating pro‐ and anti‐apoptotic biomarkers. Significance: The combination treatment with curcumin results in achieving the desired anti‐cancerous effect of Dox without compromising its activity and hence, reduces the possibility of its dose mediated cardiotoxic effects. Hence, curcumin holds a great potential for cardio‐oncological therapeutic interventions.

Composition of Functional Food in World Diet

The interest of researchers and consumers for functional food is rapidly growing along with exhaustive research to find out the properties and applications that are beneficial to human health. The main reason for growth of functional food market is the lifestyle and ever-growing population. With competition at every level, at times health takes the last seat which effects life in the long run. Today in twenty-first century, obesity is recognized as a global issue which has severely affected the United States, followed by India. Genetics play a major role in the development of diseases, but today lifestyle has a dominant effect. This chapter analyzes the current Indian market situation for function foods as compared to the market across the globe. It also covers the major food segments that are now regarded as functional foods. Probiotics, some fruits and vegetables, and beverages like green tea and wine are regarded as functional food. Lastly, the chapter also talks about the challenges and future aspects of functional foods.

Comprehensive Assessment of Curcumin as a Functional Food

The importance of bioactive compounds present in natural sources has withdrawn ample attention in human nutrition and established as “functional food” in the field of food chemistry and as “preventive medicine” in the field of pharmacology and healthcare. Curcumin is one such promising and well-studied natural bioactive plant compound that is present in Curcuma longa and known for providing various protective effects in different diseased states. This chapter highlights the present understanding of various protective effects of curcumin in wide range of diseases including cancer, cardiovascular diseases, diabetes, obesity, Alzheimer’s disease, etc. The major emphasis is on the molecular pathways associated with curcumin-mediated effects. The significance of its unique structure attributing to its function and present advances in curcumin applications to overcome its limitations has also been discussed in detail.

Anti-hypotensive drug induced cardiotoxicity: an in vitro study

Cardiotoxic side effects of broad range of drugs have emerged as an important cause of developing cardiovascular complications, as patients recover from one disease but develop another. Both cardiovascular and non-cardiovascular drugs may lead to the toxicity in the heart. Many drugs were initially not screened for cardiotoxicity, which is now an essential concern for drug discovery. Levophed is used for treating hypotension in critical care patients. Being a neurotransmitter, its concentration increases significantly in stress conditions and administration of this drug to patients’ results in developing acute as well as persistent cardiac complications. Therefore, understanding its concentration-mediated effects and identifying the toxic concentration will serve as a platform to develop interventions to prevent adverse drug effects. In the present study, concentration and time-dependent effects of Levophed in H9C2 cardiomyoblasts were studied in detail by various cytotoxicity assays. Norepinephrine as a Levophed substitute was used and apoptotic cellular death was characterized by Annexin V and TUNEL DNA fragmentation assays. Morphological alterations, growth inhibition, and cellular death were also studied in detail. We observed that Levophed induces concentration-mediated deleterious effects in cardiomyoblasts. In-depth analysis of these effects will help in designing strategies in near future to combat and reduce this drug-induced cardiac toxicity.

Curcumin-mediated effects on anti-diabetic drug-induced cardiotoxicity

The present study was designed to compare the cardiotoxicity of two very commonly used anti-diabetic drugs namely pioglitazone (Pio) and metformin (Met); and to study the effects of curcumin (Curc) against these drug-induced cardiotoxicity. Curc, being an anti-oxidant molecule and having cardio-protective potential, can have promising synergistic effects in reducing the cardiac stress induced by anti-diabetic therapies. Various dose and time-dependent cell viability and oxidative stress assays were conducted to study cardiotoxic side-effects and Curc-mediated effects in cardiomyoblasts. Effects of Curc were also studied in hyperglycaemia induced cardiac stress in the presence of drugs. Quantitative assays for cell growth, reactive oxygen species (ROS) generation, lipid peroxidation and mitochondrial permeability followed by anti-oxidant enzymes and caspases activity assays were done to study the mechanism of action of the induced cardiotoxicity. Significant dose and time mediated deleterious effects of Pio and Met were witnessed. Oxidative stress studies showed a remarkable increase in ROS with increasing dose of anti-diabetic drugs. Increased caspase activity and altered mitochondrial integrity were also witnessed in presence of Met and Pio in cardiomyoblasts. These alterations were found to be significantly reduced when treated with Curc simultaneously. The study confirms that Met and Pio exert toxic effects on cardiac cells by generating oxidative stress. Curc, being an anti-oxidative molecule, can suppress this effect and, therefore, can be used as a supplement with anti-diabetic drugs to suppress the induced cardiac stress.

Natural Polyphenols as Prospective Inhibitors for MMPs Remodeling in Human Diseases

ECM composition and turnover is carefully regulated by various proteases, among which the most important are matrix metalloproteinases (MMPs). Many MMP inhibitors have been followed as clinical applicants for targeting MMPs, but most of these studies have failed during clinical trials due to side effects resulting from broad-spectrum inhibition and inefficiency of inhibitors and regulation of MMPs during diseases is very complicated. Development of MMPs inhibitors from natural products showed beneficial effects in various diseases like cancer, cardiovascular, skin-aging, neurodegenerative diseases, and other. These natural products include secondary metabolites of edible and nonedible plants, such as polyphenols, monophenols, and others. Polyphenols are ample micronutrients in our diet and its beneficial effects depend on the quantity consumed and on their bioavailability. In this chapter, the various types of polyphenols, such as flavonoids, curcuminoids, phenolic acids, etc. and their biological activity to regulate the MMPs in cancer, cardiovascular and other diseases are reviewed.