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Fulltext Bioaccumulation and potential sources of heavy metal contamination in fish species in River Ganga basin: Possible human health risks evaluation

Maurya PK, Malik DS, Yadav KK, Kumar A, Kumar S, Kamyab H

Toxicol Rep, 2019;6:472-481.
PMID: 31193923 DOI: 10.1016/j.toxrep.2019.05.012

This paper assesses the potential human health risks posed by five heavy metals (Zn, Pb, Cu, Cd, and Cr) found in seven most consumable fish species (Cirrhinus mrigala, Cirrhinus reba, Catla catla, Lebio rohita, Crossocheilus latius, Clupisoma garua, and Mystus tengara) collected from local markets of Varanasi, Allahabad, Mirzapur, and Kanpur of Uttar Pradesh, India. The Cu concentration was found at Varanasi (4.58 mg/l), Allahabad (2.54 mg/l), and Mirzapur (2.54 mg/l). Pb was recorded 0.54, 0.62, 0.85, and 0.24 mg/l at Kanpur, Allahabad, Mirzapur, and Varanasi, respectively. The Cd concentration was recorded 0.54, 0.68, 0.78, and 0.85 mg/l at Kanpur, Allahabad, Mirzapur, and Varanasi, respectively. The Cr, Cd, and Pb concentrations in the river water were observed over the prescribed safe limits at all sampling sites, while Cu concentration was higher than the standards at all sites except Kanpur. However, Zn was observed under the permissible limits (15 mg/l) at all sampling sites. In case of fish tissues, WHO reported the concentration of Pb, Cd, and Cr higher than the prescribed safe limits. The results determined that the highest heavy metals accumulation was found settled in the liver of all selected fish species. Zn ranked the highest quantity, which was found in fish tissues with the concentration of 32.41 ± 2.55 μg/g in the gill of C. catla and 4.77 ± 0.34 μg/g in the gill C. Reba. The metals followed the magnitude order of Zn > Pb > Cu > Cd > Cr in selected fish tissues.
Identification of biomarkers and genetic approaches toward chronic obstructive pulmonary disease

Wadhwa R, Aggarwal T, Malyla V, Kumar N, Gupta G, Chellappan DK, et al.

J Cell Physiol, 2019 08;234(10):16703-16723.
PMID: 30912142 DOI: 10.1002/jcp.28482

Chronic obstructive pulmonary disease accounts as the leading cause of mortality worldwide prominently affected by genetic and environmental factors. The disease is characterized by persistent coughing, breathlessness airways inflammation followed by a decrease in forced expiratory volume1 and exacerbations, which affect the quality of life. Determination of genetic, epigenetic, and oxidant biomarkers to evaluate the progression of disease has proved complicated and challenging. Approaches including exome sequencing, genome-wide association studies, linkage studies, and inheritance and segregation studies played a crucial role in the identification of genes, their pathways and variation in genes. This review highlights multiple approaches for biomarker and gene identification, which can be used for differential diagnosis along with the genome editing tools to study genes associated with the development of disease and models their function. Further, we have discussed the approaches to rectify the abnormal gene functioning of respiratory tissues and various novel gene editing techniques like Zinc finger nucleases (ZFN), transcription activator-like effector nucleases (TALEN), and clustered regulatory interspaced short palindromic repeats/CRISPR-associated protein 9 (CRISPR/Cas9).
MicroRNAs as Biomarker for Breast Cancer

Aggarwal T, Wadhwa R, Gupta R, Paudel KR, Collet T, Chellappan DK, et al.

Endocr Metab Immune Disord Drug Targets, 2020;20(10):1597-1610.
PMID: 32342824 DOI: 10.2174/1871530320666200428113051

Regardless of advances in detection and treatment, breast cancer affects about 1.5 million women all over the world. Since the last decade, genome-wide association studies (GWAS) have been extensively conducted for breast cancer to define the role of miRNA as a tool for diagnosis, prognosis and therapeutics. MicroRNAs are small, non-coding RNAs that are associated with the regulation of key cellular processes such as cell multiplication, differentiation, and death. They cause a disturbance in the cell physiology by interfering directly with the translation and stability of a targeted gene transcript. MicroRNAs (miRNAs) constitute a large family of non-coding RNAs, which regulate target gene expression and protein levels that affect several human diseases and are suggested as the novel markers or therapeutic targets, including breast cancer. MicroRNA (miRNA) alterations are not only associated with metastasis, tumor genesis but also used as biomarkers for breast cancer diagnosis or prognosis. These are explained in detail in the following review. This review will also provide an impetus to study the role of microRNAs in breast cancer.
Fluoride contamination, health problems and remediation methods in Asian groundwater: A comprehensive review

Yadav KK, Kumar S, Pham QB, Gupta N, Rezania S, Kamyab H, et al.

Ecotoxicol Environ Saf, 2019 Oct 30;182:109362.
PMID: 31254856 DOI: 10.1016/j.ecoenv.2019.06.045

In low concentration, fluoride is considered a necessary compound for human health. Exposure to high concentrations of fluoride is the reason for a serious disease called fluorosis. Fluorosis is categorized as Skeletal and Dental fluorosis. Several Asian countries, such as India, face contamination of water resources with fluoride. In this study, a comprehensive overview on fluoride contamination in Asian water resources has been presented. Since water contamination with fluoride in India is higher than other Asian countries, a separate section was dedicated to review published articles on fluoride contamination in this country. The status of health effects in Asian countries was another topic that was reviewed in this study. The effects of fluoride on human organs/systems such as urinary, renal, endocrine, gastrointestinal, cardiovascular, brain, and reproductive systems were another topic that was reviewed in this study. Different methods to remove fluoride from water such as reverse osmosis, electrocoagulation, nanoﬁltration, adsorption, ion-exchange and precipitation/coagulation were introduced in this study. Although several studies have been carried out on contamination of water resources with fluoride, the situation of water contamination with fluoride and newly developed technology to remove fluoride from water in Asian countries has not been reviewed. Therefore, this review is focused on these issues: 1) The status of fluoride contamination in Asian countries, 2) health effects of fluoride contamination in drinking water in Asia, and 3) the existing current technologies for defluoridation in Asia.
Interactions with the macrophages: An emerging targeted approach using novel drug delivery systems in respiratory diseases

Mehta M, Deeksha, Sharma N, Vyas M, Khurana N, Maurya PK, et al.

Chem Biol Interact, 2019 May 01;304:10-19.
PMID: 30849336 DOI: 10.1016/j.cbi.2019.02.021

Macrophages are considered as the most flexible cells of the hematopoietic system that are distributed in the tissues to act against pathogens and foreign particles. Macrophages are essential in maintaining homeostatic tissue processes, repair and immunity. Also, play important role in cytokine secretion and signal transduction of the infection so as to develop acquired immunity. Accounting to their involvement in pathogenesis, macrophages present a therapeutic target for the treatment of inflammatory respiratory diseases. This review focuses on novel drug delivery systems (NDDS) including nanoparticles, liposomes, dendrimers, microspheres etc that can target alveolar macrophage associated with inflammation, intracellular infection and lung cancer. The physiochemical properties and functional moieties of the NDDS attributes to enhanced macrophage targeting and uptake. The NDDS are promising for sustained drug delivery, reduced therapeutic dose, improved patient compliance and reduce drug toxicity. Further, the review also discuss about modified NDDS for specificity to the target and molecular targeting via anti-microbial peptides, kinases, NRF-2 and phosphodiesterase.
Increasing complexity and interactions of oxidative stress in chronic respiratory diseases: An emerging need for novel drug delivery systems

Dua K, Malyla V, Singhvi G, Wadhwa R, Krishna RV, Shukla SD, et al.

Chem Biol Interact, 2019 Feb 01;299:168-178.
PMID: 30553721 DOI: 10.1016/j.cbi.2018.12.009

Oxidative stress is intensely involved in enhancing the severity of various chronic respiratory diseases (CRDs) including asthma, chronic obstructive pulmonary disease (COPD), infections and lung cancer. Even though there are various existing anti-inflammatory therapies, which are not enough to control the inflammation caused due to various contributing factors such as anti-inflammatory genes and antioxidant enzymes. This leads to an urgent need of novel drug delivery systems to combat the oxidative stress. This review gives a brief insight into the biological factors involved in causing oxidative stress, one of the emerging hallmark feature in CRDs and particularly, highlighting recent trends in various novel drug delivery carriers including microparticles, microemulsions, microspheres, nanoparticles, liposomes, dendrimers, solid lipid nanocarriers etc which can help in combating the oxidative stress in CRDs and ultimately reducing the disease burden and improving the quality of life with CRDs patients. These carriers improve the pharmacokinetics and bioavailability to the target site. However, there is an urgent need for translational studies to validate the drug delivery carriers for clinical administration in the pulmonary clinic.
The potential of siRNA based drug delivery in respiratory disorders: Recent advances and progress

Dua K, Wadhwa R, Singhvi G, Rapalli V, Shukla SD, Shastri MD, et al.

Drug Dev Res, 2019 09;80(6):714-730.
PMID: 31691339 DOI: 10.1002/ddr.21571

Lung diseases are the leading cause of mortality worldwide. The currently available therapies are not sufficient, leading to the urgent need for new therapies with sustained anti-inflammatory effects. Small/short or silencing interfering RNA (siRNA) has potential therapeutic implications through post-transcriptional downregulation of the target gene expression. siRNA is essential in gene regulation, so is more favorable over other gene therapies due to its small size, high specificity, potency, and no or low immune response. In chronic respiratory diseases, local and targeted delivery of siRNA is achieved via inhalation. The effectual delivery can be attained by the generation of aerosols via inhalers and nebulizers, which overcomes anatomical barriers, alveolar macrophage clearance and mucociliary clearance. In this review, we discuss the different siRNA nanocarrier systems for chronic respiratory diseases, for safe and effective delivery. siRNA mediated pro-inflammatory gene or miRNA targeting approach can be a useful approach in combating chronic respiratory inflammatory conditions and thus providing sustained drug delivery, reduced therapeutic dose, and improved patient compliance. This review will be of high relevance to the formulation, biological and translational scientists working in the area of respiratory diseases.
Emerging Complexity and the Need for Advanced Drug Delivery in Targeting Candida Species

Wadhwa R, Pandey P, Gupta G, Aggarwal T, Kumar N, Mehta M, et al.

Curr Top Med Chem, 2019;19(28):2593-2609.
PMID: 31746290 DOI: 10.2174/1568026619666191026105308

BACKGROUND: Candida species are the important etiologic agents for candidiasis, the most prevalent cause of opportunistic fungal infections. Candida invasion results in mucosal to systemic infections through immune dysfunction and helps in further invasion and proliferation at several sites in the host. The host defence system utilizes a wide array of the cells, proteins and chemical signals that are distributed in blood and tissues which further constitute the innate and adaptive immune system. The lack of antifungal agents and their limited therapeutic effects have led to high mortality and morbidity related to such infections.
METHODS: The necessary information collated on this review has been gathered from various literature published from 1995 to 2019.
RESULTS: This article sheds light on novel drug delivery approaches to target the immunological axis for several Candida species (C. albicans, C. glabrata, C. parapsilosis, C. tropicalis, C. krusei, C. rugose, C. hemulonii, etc.).
CONCLUSION: It is clear that the novel drug delivery approaches include vaccines, adoptive transfer of primed immune cells, recombinant cytokines, therapeutic antibodies, and nanoparticles, which have immunomodulatory effects. Such advancements in targeting various underpinning mechanisms using the concept of novel drug delivery will provide a new dimension to the fungal infection clinic particularly due to Candida species with improved patient compliance and lesser side effects. This advancement in knowledge can also be extended to target various other similar microbial species and infections.