Browsing by Author "Amit Kumar Tripathi"

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Acute Febrile Illness in India: An Epidemiological Retrospective Study
(Bentham Science Publishers, 2025) Kaushalendra Kumar; Amit Kumar Tripathi; Vikas Kumar Sharma; Sunil Kumar Mishra; Ranjana Saksena Patnaik
Introduction: Acute febrile illness (AFI) is a frequent occurrence in India, often complicated by a multitude of pathogenic and etiological factors. In this context, it is important to analyze the biochemical, hematological, and epidemiological clinical parameters of AFI patients in the North Indian population. Methods: This study included 1,819 patients of various ages who presented with new-onset acute febrile illness (AFI) between 2017 and 2021. Among these patients, 211, with a median age of 40 years (ranging from 2 to 85 years), were selected for further analysis. At enrollment, clinical examination involved collecting respiratory tract specimens, blood, and urine samples for biochemical analysis, with subsequent data analysis conducted using statistical methods. Results and Discussion: The following biochemical parameters were analyzed: C-reactive protein (CRP), alkaline phosphatase (ALP), serum glutamate-pyruvate transaminase (SGPT), serum glutamic oxaloacetic transaminase (SGOT), gamma-glutamyl transpeptidase (GGT), and total protein serum. The hematological parameters included total leukocyte count (TLC), lymphocyte count, monocyte count, eosinophil count, red blood cell count (RBCs), packed cell volume (PCV), erythrocyte sedimentation rate (ESR), hematocrit value, mean corpuscular volume (MCV), and mean corpuscular hemoglobin (MCH). Additionally, clinical parameters such as phosphorus, urea, calcium, sodium, uric acid, bilirubin, and potassium were measured. Specific values observed were: SGPT (~113 IU/L in 2018), SGOT (~81 U/L in 2019), GGT (~148 g/L in 2018), and total protein serum (~7 g/L in 2020). The hematological parameters (TLC, lymphocyte, monocyte, RBCs, PCV, ESR, MCV, and MCH). The regression analysis was conducted to explore the temperature recorded at the time of admission, the duration of hospital stays, and biochemical as well as hematological variables of patients suffering from AFI. Karl-Pearson's correlation coefficient and variance inflation factor for each variable mentioned above. Conclusion: Biochemical and hematological parameters were analyzed over different years of intake in patients with Acute Febrile Illness (AFI). Further investigation is required to explore the mechanistic pathways of infection, and preventive measures will be implemented using natural products and other therapeutic interventions. Our data will offer the first systematic assessment of the etiological factors, along with regression analysis and the Karl-Pearson correlation coefficient for each variable in AFI patients. © 2025 Bentham Science Publishers.
Climate Change and Its Impact on Forest of Indian Himalayan Region: A Review
(Springer Science and Business Media B.V., 2022) Amit Kumar Tripathi; Prem Chandra Pandey; Jyoti Kumar Sharma; Dimitris Triantakonstantis; Prashant K. Srivastava
The Indian Himalayan Region (IHR) forms the northern boundary of India covering an area of about 5.3 lakh km2, which constitutes 16.2% of the total geographical area. The region is remarkable for its diversity of plants and animals and provides abundant ecosystem services to people. The Indian Himalayas (IH) is richly endowed with forest resources and supports different types of forest ecosystems along with varied topography. In addition to anthropogenic factors, the forests of IH are under pressure due to changing climate. There are several pieces of evidence of significant changes in temperature, precipitation, and vegetation phenology in IHR. Climate change (CC) has a significant impact on forest ecosystems of IH which results in the upward movement of several plant species, and further changes are expected to cause the extinction of species. Due to changing climatic conditions in IHR, possibly some of the locations may become more favorable to alien invasive species causing negative impacts on native plants. Changing temperature and rainfall in the region have caused phenological changes in many economically and ecologically important plant species like Rhododendron sp., Myrica esculenta, Pinus wallichiana, etc. As a result of which these species are shifting towards higher elevations to cope up with altered climate. A significant reduction in suitable habitat and the massive decline in the population of animal species due to climate change is also predicted. The studies carried out in IHR indicated shifts in vegetation types across IHR from moderate to large scale. Higher elevation Himalayan temperate forests, subalpine forests, and alpine forests are more vulnerable to the adverse effects of climate change while Sal forests are predicted to shift towards the north-eastern region. Western Himalayan forests are highly susceptible to changing climate while eastern Himalayan forests are estimated to be more resilient. © 2022, The Author(s), under exclusive license to Springer Nature Switzerland AG.
Correction to: PLGA-Quercetin Nano-Formulation Inhibits Cancer Progression via Mitochondrial Dependent Caspase-3,7 and Independent FoxO1 Activation with Concomitant PI3K/AKT Suppression (Pharmaceutics, (2022), 14, 7, (1326), 10.3390/pharmaceutics14071326)
(Multidisciplinary Digital Publishing Institute (MDPI), 2024) Neera Yadav; Amit Kumar Tripathi; Amna Parveen; Shama Parveen; Monisha Banerjee
In the published publication [1], there was an error regarding the affiliation for Neera Yadav. In addition to affiliation 1, the updated affiliation should include: Molecular and Human Genetics Lab, Department of Zoology, University of Lucknow, Lucknow 226007, India. Neera Yadav did not act as the corresponding author any more. Shama Parveen and Monisha Banerjee (the corresponding author) were not included as authors in the original publication [1]. The corrected Author Contributions statement appears here. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor. The original publication has also been updated. Shama Parveen: investigation, formal analysis, methodology; Monisha Banerjee: project administration, funding acquisition, resources, supervision, writing—review and editing. The authors also acknowledge Ratan Singh Ray, CSIR-Indian Institute of Toxicology Research (IITR), Lucknow, India, for the synthesis of nanoparticles; Birbal Sahni Institute of Palaeosciences (BSIP), Lucknow, for the SEM facility; Centre of Excellence, Higher Education Government of Uttar Pradesh for the cell culture facility at the Molecular and Human Genetics Laboratory, Department of Zoology, University of Lucknow, Lucknow-226007, India. The authors state that the scientific conclusions are unaffected. This correction was approved by the Academic Editor and Editor-in-Chief. The original publication has also been updated. © 2024 by the authors.
Green synthesis of silver nanoparticles using Trema Orientalis (L.) extract and evaluation of their antibacterial activity
(Taylor and Francis Ltd., 2025) Richa Das; Pradeep Harish Kumar; Amit Kumar Singh; Shreni Agrawal; S. Albukhaty; Indrani Bhattacharya; Kavindra Nath Tiwari; Sunil Kumar Mishra; Amit Kumar Tripathi; Faizah A. AlMalki; Azalldeen Kazal Alzubaidi; Wasan J. Al-Kaabi; Vishnu D. Rajput; Zaidon T. Al-Aqbi
A novel green method was developed to create pure, safe, and stable silver nanoparticles (AgNPs) using Trema orientalis (L.) leaf extract as a reducing and stabilizing agent and evaluated its antibacterial activity. UV-vis spectroscopy indicated the biogenesis of AgNPs based on the absorbance in the range of 400–500 nm. The Fourier transform infrared spectroscopy (FTIR) revealed that flavonoids play a crucial role in the synthesis and stability of green AgNPs, serving as the primary phytoconstituents involved. AgNPs were spherical, and crystalline in nature. The size ranged from 14.04–34.38 nm as determined by transmission electron microscopy (TEM). For phase determination of the crystalline structure, AgNPs were subjected to X-ray diffraction (XRD). The crystallinity percentage calculated was 79.28%. The investigation using atomic force microscopy (AFM) measured the average roughness, maximum height, and valley depth of AgNPs. The mean surface roughness measured was 12.054 nm. The well diffusion method demonstrated the antibacterial activity of AgNPs against Staphylococcus aureus, resulting in inhibition zones measuring 9, 10, 13, and 14 mm. These effects were observed at concentrations of 25 µg/mL, 50 µg/mL, 75 µg/mL, and 100 µg/mL, respectively. The minimum inhibitory concentration observed against S. aureus was 55.31 μg/ml. This work provides a more sustainable and efficient method of bacterial treatment. © 2024 The Author(s). Published by Informa UK Limited, trading as Taylor & Francis Group.
In silico and network pharmacology analysis of fucosterol: a potent anticancer bioactive compound against HCC
(Springer, 2024) Kajal Singh; Pradeep Kumar; Amit Kumar Singh; Nancy Singh; Sakshi Singh; Kavindra Nath Tiwari; Shreni Agrawal; Richa Das; Anuradha Singh; Bhuwal Ram; Amit Kumar Tripathi; Sunil Kumar Mishra
The Fucaceae family of marine brown algae includes Ascophyllum nodosum. Fucosterol (FSL) is a unique bioactive component that was identified through GC-MS analysis of the hydroalcoholic extract of A. nodosum. Fucosterol's mechanism of action towards hepatocellular cancer was clarified using network pharmacology and docking study techniques. The probable target gene of FSL has been predicted using the TargetNet and SwissTargetPred databases. GeneCards and the DisGNet database were used to check the targeted genes of FSL. By using the web programme Venny 2.1, the overlaps of FSL and HCC disease demonstrated that 18 genes (1.3%) were obtained as targeted genes Via the STRING database, a protein–protein interaction (PPI) network with 18 common target genes was constructed. With the aid of CytoNCA, hub genes were screened using the Cytoscape software, and the targets' hub genes were exported into the ShinyGo online tool for study of KEGG and gene ontology enrichment. Using the software AutoDock, a hub gene molecular docking study was performed. Ten genes, including AR, CYP19A1, ESR1, ESR2, TNF, PPARA, PPARG, HMGCR, SRC, and IGF1R, were obtained. The 10 targeted hubs docked with FSL successfully. The active components FSL of ASD, the FSL, are engaged in fatty liver disease, cancer pathways, and other signalling pathways, which could prove beneficial for the management of HCC. © The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature 2024.
Molecular and pharmacological aspects of piperine as a potential molecule for disease prevention and management: evidence from clinical trials
(Springer Science and Business Media Deutschland GmbH, 2022) Amit Kumar Tripathi; Anup Kumar Ray; Sunil Kumar Mishra
Background: Piperine is a type of amide alkaloid that exhibits pleiotropic properties like antioxidant, anticancer, anti-inflammatory, antihypertensive, hepatoprotective, neuroprotective and enhancing bioavailability and fertility-related activities. Piperine has the ability to alter gastrointestinal disorders, drug-metabolizing enzymes, and bioavailability of several drugs. The present review explores the available clinical and preclinical data, nanoformulations, extraction process, structure–activity relationships, molecular docking, bioavailability enhancement of phytochemicals and drugs, and brain penetration properties of piperine in the prevention, management, and treatment of various diseases and disorders. Main body: Piperine provides therapeutic benefits in patients suffering from diabetes, obesity, arthritis, oral cancer, breast cancer, multiple myeloma, metabolic syndrome, hypertension, Parkinson's disease, Alzheimer’s disease, cerebral stroke, cardiovascular diseases, kidney diseases, inflammatory diseases, and rhinopharyngitis. The molecular basis for the pleiotropic activities of piperine is based on its ability to regulate multiple signaling molecules such as cell cycle proteins, anti-apoptotic proteins, P-glycoprotein, cytochrome P450 3A4, multidrug resistance protein 1, breast cancer resistance protein, transient receptor potential vanilloid 1 proinflammatory cytokine, nuclear factor-κB, c-Fos, cAMP response element-binding protein, activation transcription factor-2, peroxisome proliferator-activated receptor-gamma, Human G-quadruplex DNA, Cyclooxygenase-2, Nitric oxide synthases-2, MicroRNA, and coronaviruses. Piperine also regulates multiple signaling pathways such as Akt/mTOR/MMP-9, 5′-AMP-activated protein kinase-activated NLR family pyrin domain containing-3 inflammasome, voltage-gated K+ current, PKCα/ERK1/2, NF-κB/AP-1/MMP-9, Wnt/β-catenin, JNK/P38 MAPK, and gut microbiota. Short conclusion: Based on the current evidence, piperine can be the potential molecule for treatment of disease, and its significance of this molecule in the clinic is discussed. Graphical abstract: [Figure not available: see fulltext.] © 2022, The Author(s).
Molecular and Therapeutic Insights of Alpha-Lipoic Acid as a Potential Molecule for Disease Prevention
(Springer Science and Business Media Deutschland GmbH, 2023) Amit Kumar Tripathi; Anup Kumar Ray; Sunil Kumar Mishra; Siddharth Mall Bishen; Hirdyesh Mishra; Aman Khurana
Alpha-lipoic acid is an organic, sulfate-based compound produced by plants, humans, and animals. As a potent antioxidant and a natural dithiol compound, it performs a crucial role in mitochondrial bioenergetic reactions. A healthy human body, on the other hand, can synthesize enough α-lipoic acid to scavenge reactive oxygen species and increase endogenous antioxidants; however, the amount of α-lipoic acid inside the body decreases significantly with age, resulting in endothelial dysfunction. Molecular orbital energy and spin density analysis indicate that the sulfhydryl (-SH) group of molecules has the greatest electron donating activity, which would be responsible for the antioxidant potential and free radical scavenging activity. α-Lipoic acid acts as a chelating agent for metal ions, a quenching agent for reactive oxygen species, and a reducing agent for the oxidized form of glutathione and vitamins C and E. α-Lipoic acid enantiomers and its reduced form have antioxidant, cognitive, cardiovascular, detoxifying, anti-aging, dietary supplement, anti-cancer, neuroprotective, antimicrobial, and anti-inflammatory properties. α-Lipoic acid has cytotoxic and antiproliferative effects on several cancers, including polycystic ovarian syndrome. It also has usefulness in the context of female and male infertility. Although α-lipoic acid has numerous clinical applications, the majority of them stem from its antioxidant properties; however, its bioavailability in its pure form is low (approximately 30%). However, nanoformulations have shown promise in this regard. The proton affinity and electron donating activity, as a redox-active agent, would be responsible for the antioxidant potential and free radical scavenging activity of the molecule. This review discusses the most recent clinical data on α-lipoic acid in the prevention, management, and treatment of a variety of diseases, including coronavirus disease 2019. Based on current evidence, the preclinical and clinical potential of this molecule is discussed. Graphical Abstract: [Figure not available: see fulltext.]. © 2023, The Author(s) under exclusive licence to Sociedade Brasileira de Farmacognosia.
Network pharmacology of apigeniflavan: a novel bioactive compound of Trema orientalis Linn. in the treatment of pancreatic cancer through bioinformatics approaches
(Springer Science and Business Media Deutschland GmbH, 2023) Richa Das; Shreni Agrawal; Pradeep Kumar; Amit Kumar Singh; Praveen Kumar Shukla; Indrani Bhattacharya; Kavindra Nath Tiwari; Sunil Kumar Mishra; Amit Kumar Tripathi
Pancreatic cancer is the seventh most prevalent cause of mortality globally. Since time immemorial, plant-derived products have been in use as therapeutic agents due to the existence of biologically active molecules called secondary metabolites. Flavonoids obtained from plants participate in cell cycle arrest, induce autophagy and apoptosis, and decrease oxidative stress in pancreatic cancer. The present study involves network pharmacology-based study of the methanolic leaf extract of Trema orientalis (MLETO) Linn. From the high-resolution mass spectrometry (HRMS) analysis, 21 nucleated flavonoids were screened out, of which only apigeniflavan was selected for further studies because it followed Lipinski’s rule and showed no toxicity. The pharmacokinetics and physiochemical characteristics of apigeniflavan were performed using the online web servers pkCSM, Swiss ADME, and ProTox-II. This is the first in silico study to report the efficiency of apigeniflavan in pancreatic cancer treatment. The targets of apigeniflavan were fetched from SwissTargetPrediction database. The targets of pancreatic cancer were retrieved from DisGeNET and GeneCards. The protein–protein interaction of the common genes using Cytoscape yielded the top five hub genes: KDR, VEGFA, AKT1, SRC, and ESR1. Upon molecular docking, the lowest binding energies corresponded to best docking score which indicated the highest protein–ligand affinity. Kyoto Encyclopaedia of Genes and Genomes (KEGG) database was employed to see the involvement of hub genes in pathways related to pancreatic cancer. The following, pancreatic cancer pathway, MAPK, VEGF, PI3K–Akt, and ErbB signaling pathways, were found to be significant. Our results indicate the involvement of the hub genes in tumor growth, invasion and proliferation in the above-mentioned pathways, and therefore necessitating their downregulation. Moreover, apigeniflavan can flourish as a promising drug for the treatment of pancreatic cancer in future. © 2023, King Abdulaziz City for Science and Technology.
Network pharmacology-based anti-pancreatic cancer potential of kaempferol and catechin of Trema orientalis L. through computational approach
(Springer, 2023) Shreni Agrawal; Richa Das; Amit Kumar Singh; Pradeep Kumar; Praveen Kumar Shukla; Indrani Bhattacharya; Amit Kumar Tripathi; Sunil Kumar Mishra; Kavindra Nath Tiwari
In pancreatic cancer, healthy cells in the pancreas begin to malfunction and proliferate out of control. According to our conventional knowledge, many plants contain several novel bioactive compounds, having pharmaceutical applications for the treatment of disease like pancreatic cancer. The methanolic fraction of fruit extract of Trema orientalis L. (MFETO) was analysed through HRMS. In this in silico study, pharmacokinetic and physicochemical properties of the identified flavonoids from MFETO were screened out by ADMET analysis. Kaempferol and catechin followed Lipinski rules and showed no toxicity in Protox II. Targets of these compounds were taken from SwissTarget prediction and TCMSP whilst targets for pancreatic cancer were taken from GeneCards and DisGeNET databases. The protein–protein interaction (PPI) network of common genes was generated through STRING and then exported to the Cytoscape to get top 5 hub genes (AKT1, SRC, EGFR, TNF, and CASP3). The interaction between compounds and hub genes was analysed using molecular docking, and high binding affinity between them can be visualised by Biovia discovery studio visualizer. Our study shows that, five hub genes related to pancreatic cancer play an important role in tumour growth induction, invasion and migration. Kaempferol effectively check cell migration by inhibiting ERK1/2, EGFR-related SRC, and AKT pathways by scavenging ROS whilst catechin inhibited TNFα-induced activation and cell cycle arrest at G1 and G2/M phases by induction of apoptosis of malignant cells. Kaempferol and catechin containing MFETO can be used for formulation of potent drugs for pancreatic cancer treatment in future. © 2023, The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.
PLGA-Quercetin Nano-Formulation Inhibits Cancer Progression via Mitochondrial Dependent Caspase-3,7 and Independent FoxO1 Activation with Concomitant PI3K/AKT Suppression
(Multidisciplinary Digital Publishing Institute (MDPI), 2022) Neera Yadav; Amit Kumar Tripathi; Amna Parveen; Shama Parveen; Monisha Banerjee
Quercetin is one of the most important plant flavanols, having several pharmacological and biological uses. Quercetin (Q) is an extremely hydrophobic phytochemical and has poor intracellular absorption, which makes its use limited. Present research demonstrates that quercetin-loaded PLGA nanoparticles (PLGA-QNPs) could overcome its low hydrophilicity and improve its anti-cancer potential. PLGA nanoparticles loaded with Q were prepared by the solvent evaporation technique and its anticancer activity was examined in vitro as well as in vivo. The cell viability was assessed through MTT assay and apoptosis was assayed through Hoechst-PI and EB/AO double staining followed by mitochondrial damage through Mito-tracker RMX-Ros. Gene expression was examined through RT-PCR. Cell cycle arrest in G2/M phase was analyzed through FACS. The results obtained revealed that PLGA-QNPs significantly reduced the viability of human cervical and breast cancer cell lines. PLGA-QNPs induced apoptosis in human cervical cancer cells in a dose dependent manner. The gene expression of PI3K/AKT was down-regulated and FoxO1 was upregulated in PLGA-QNP-treated cells, which showed a high expression level of active Caspase-3 and 7, which are responsible for apoptosis. In addition, PLGA-QNPs reduced the average number of tumors and prolonged the tumor latency period in DMBA-induced mammary adenocarcinoma SD rats. These findings suggest that PLGA-QNPs inhibit cervical and breast cancer progression via mitochondrial dependent Caspase-3 and 7 and mitochondrial independent FoxO1 activation with concomitant suppression of the PI3K/AKT pathway. For future studies, we suggest that potential druggability efficacy and clinical development of anticancer PLGA-QNPs need to be evaluated intensely for successful anticancer drug development. © 2022 by the authors. Licensee MDPI, Basel, Switzerland.
Preface
(Springer Singapore, 2020) Ashish Dwivedi; Neeraj Agarwal; Lipika Ray; Amit Kumar Tripathi
[No abstract available]
Rodent Stroke Model Guidelines: An Update
(Springer Singapore, 2021) Amit Kumar Tripathi; Ravi Shankar Singh; Awakash Soni; Rajavashisth Tripathi; Ranjana Patnaik
According to a recent statistical report from the American Heart Association (AHA), stroke is the fifth major reason for mortality and morbidity. Stroke is a devastating clinical condition for which efficient interventions are not currently available. The rodent stroke model has critical significance in a series of preclinical tests for neuroprotection, neurotransmitters, and neuroplasticity studies. Despite using animal modeling in neuroprotective research, their modeling, development, and preclinical evaluation of animals have been rarely and consistently demonstrated. Comorbidities like aging, diabetes, hypertension, and smoking are major contributors to stroke and the use of comorbid rodent models of stroke is clinically relevant to the human disease condition. Animals, like hypertensive rats and diabetic mice, these comorbid models, are used to explore the pathophysiology of cerebral stroke. Regional cerebral blood flow (rCBF) real-time tracking of arterial blood flow by using laser Doppler flowmetry (LDF) provide evidence for the success of middle cerebral artery (MCA) occlusion. Several factors play an important role in neurological outcomes, while have not happened before effectively addressed in Stroke Therapy Academic Industry Roundtable (STAIR) recommendations. Here, we describe the general guiding principle for a preclinical stroke model, STAIR committee recommendation, the procedure to develop intraluminal Middle Cerebral Artery Occlusion (MCAO) in rodent, surgical procedure optimization, MCA occluders like silicone-rubber coated, nylon coated, nail-polish coated, methyl methacrylate coated, poly-L-Lysine (PLL) coated and resin-coated and their physical properties. Besides, we will provide information on neurobehavior assessment, neuroprotection by volatile anesthesia molecule (halothane, isoflurane, desflurane, sevoflurane, and ketamine/xylazine cocktail), hypothermia induced neuroprotection, and hyperthermia damaging effect on ischemic injury. © The Editor(s) (if applicable) and The Author(s), under exclusive license to Springer Nature Singapore Pte Ltd. 2021.
Skin aging & cancer: Ambient UV-R exposure
(Springer Singapore, 2020) Ashish Dwivedi; Neeraj Agarwal; Lipika Ray; Amit Kumar Tripathi
This book summarizes the potent effect of ultraviolet radiation (UVR) on the photoaging and cancer formation. Skin is the largest human organ which continually reconstructs itself to ensure its viability, integrity, and ability to provide protection for the body. This protection can be compromised by the aging of the skin which ultimately promotes skin inflammation, impaired wound repair, and increased risk of skin cancer. The book entails mechanistic insights into the UVR-induced immunomodulation and DNA damage in the skin to delineate the pathogenesis, and develop novel ways for prevention of photoaging of the skin cells. It also elucidates the potential of nanotechnology in the treatment of skin cancer. Further, it discusses the bioinformatics approaches to understand the molecular mechanism of photoaging and cancer formation. © Springer Nature Singapore Pte Ltd. 2019.
Ultraviolet radiation (UVR): An introduction
(Springer Singapore, 2018) Ashish Dwivedi; Amit Kumar Tripathi; Jyoti Singh; Manish Kumar Pal
Radiant energy of sun is essential to perform metabolic processes of all flora and fauna on the earth. The electromagnetic radiations (EMR) emitted by sun extend from very long wavelength radiation, such as radiowaves (A ″' 3 x 108 m), to very short wavelength radiation, such as cosmic rays (A ″' 3 x 10-19 m). The EMR reaching at the earth surface contains wavelength from 290 to 4000 nm. However, the UV portion covers from 200 to 400 nm. The range from 200 to 400 nm is often arbitrarily categorized into UVA, UVB, and UVC radiation. Solar radiation less than 290 nm does not reach at the earth's surface due to the presence of O3 layer in stratospheric zone. But, last from few decades due to anthropogenic activities, the concentration of ozone layer decreases on stratospheric zone. As a consequence of that, UVB radiation levels are rising to 1% a year. Thus, the deleterious health effects on human beings (skin aging, cataracts, skin cancer, and immune suppression) are enhanced by UVR. © Springer Nature Singapore Pte Ltd. 2018.