Oxidative Stress and Antioxidants in Disease and Cancer: A Review

Gupta, Rakesh Kumar,Patel, Amit Kumar,Shah, Niranjan,Choudhary, Arun Kumar,Jha, Uday Kant,Yadav, Uday Chandra,Gupta, Pavan Kumar,Pakuwal, Uttam Asian Pacific Journal of Cancer Prevention 2014 Asian Pacific journal of cancer prevention Vol.15 No.11

Reactive oxygen species (ROS), highly reactive molecules, are produced by living organisms as a result of normal cellular metabolism and environmental factors, and can damage nucleic acids and proteins, thereby altering their functions. The human body has several mechanisms to counteract oxidative stress by producing antioxidants. A shift in the balance between oxidants and antioxidants in favor of oxidants is termed as "oxidative stress". Paradoxically, there is a large body of research demonstrating the general effect of oxidative stress on signaling pathways, less is known about the initial and direct regulation of signaling molecules by ROS, or what we term the "oxidative interface." This review focuses on the molecular mechanisms through which ROS directly interact with critical signaling molecules to initiate signaling in a broad variety of cellular processes, such as proliferation and survival (MAP kinases and PI3 kinase), ROS homeostasis, and antioxidant gene regulation (Ref-1 and Nrf-2). This review also deals with classification as well as mechanisms of formation of free radicals, examining their beneficial and deleterious effects on cellular activities and focusing on the potential role of antioxidants in preventing and repairing damage caused by oxidative stress. A discussion of the role of phytochemical antioxidants in oxidative stress, disease and the epigenome is included.

Induction of Mitochondrial-Mediated Apoptosis by Morinda Citrifolia (Noni) in Human Cervical Cancer Cells

Gupta, Rakesh Kumar,Banerjee, Ayan,Pathak, Suajta,Sharma, Chandresh,Singh, Neeta Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.1

Cervical cancer is the second most common cause of cancer in women and has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have anti-cancer properties. In this study, we used Noni, cisplatin, and the two in combination to study their cytotoxic and apoptosis-inducing effects in cervical cancer HeLa and SiHa cell lines. We demonstrate here, that Noni/Cisplatin by themselves and their combination were able to induce apoptosis in both these cell lines. Cisplatin showed slightly higher cell killing as compared to Noni and their combination showed additive effects. The observed apoptosis appeared to be mediated particularly through the up-regulation of p53 and pro-apoptotic Bax proteins, as well as down-regulation of the anti-apoptotic Bcl-2, Bcl-$X_L$ proteins and survivin. Augmentation in the activity of caspase-9 and -3 was also observed, suggesting the involvement of the intrinsic mitochondrial pathway of apoptosis for both Noni and Cisplatin in HeLa and SiHa cell lines.

Influence of Morinda citrifolia (Noni) on Expression of DNA Repair Genes in Cervical Cancer Cells

Gupta, Rakesh Kumar,Bajpai, Deepti,Singh, Neeta Asian Pacific Journal of Cancer Prevention 2015 Asian Pacific journal of cancer prevention Vol.16 No.8

Background: Previous studies have suggested that Morinda citrifolia (Noni) has potential to reduce cancer risk. Objective: The purpose of this study was to investigate the effect of Noni, cisplatin, and their combination on DNA repair genes in the SiHa cervical cancer cell line. Materials and Methods: SiHa cells were cultured and treated with 10% Noni, $10{\mu}g/dl$ cisplatin or their combination for 24 hours. Post culturing, the cells were pelleted, RNA extracted, and processed for investigating DNA repair genes by real time PCR. Results: The expression of nucleotide excision repair genes ERCC1, ERCC2, and ERCC4 and base excision repair gene XRCC1 was increased 4 fold, 8.9 fold, 4 fold, and 5.5 fold, respectively, on treatment with Noni as compared to untreated controls (p<0.05). In contrast, expression was found to be decreased 22 fold, 13 fold, 16 fold, and 23 fold on treatment with cisplatin (p<0.05). However, the combination of Noni and cisplatin led to an increase of 2 fold, 1.6 fold, 3 fold, 1.2 fold, respectively (p<0.05). Conclusions: Noni enhanced the expression of DNA repair genes by itself and in combination with cisplatin. However, high expression of DNA repair genes at mRNA level only signifies efficient DNA transcription of the above mentioned genes; further investigations are needed to evaluate the DNA repair protein expression.

Morinda citrifolia (Noni) Alters Oxidative Stress Marker and Antioxidant Activity in Cervical Cancer Cell Lines

Gupta, Rakesh Kumar,Singh, Neeta Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Background: Cervical cancer, the second most common cancer in women, has a high mortality rate. Cisplatin, an antitumor agent, is generally used for its treatment. However, the administration of cisplatin is associated with side effects and intrinsic resistance. Morinda citrifolia (Noni), a natural plant product, has been shown to have antioxidant activities in vitro and in vivo. Materials and Methods: Both HeLa and SiHa cervical cancer cell lines were treated with 10% Noni, 10 mg/dl cisplatin, or a combination of both 10% Noni and 10 mg/dl cisplatin for 24 hours. Post culturing, the cells were pelleted and stored at $-70^{\circ}C$ for malondialdehyde and catalase assays. Results: On treatment with Noni, CP, and their combination, the level of MDA decreased by 0.76 fold, 0.49 fold, and 0.68 fold respectively in HeLa cells; and by 0.93 fold, 0.67 fold, and 0.79 fold respectively in SiHa cells, as compared to their controls; whereas catalase activity increased by 1.61 fold, 0.54 fold, and 2.35 fold, respectively in HeLa cells; and by 0.98 fold, 0.39 fold, and 1.85 fold respectively in SiHa cells. Conclusions: A decrease in level of lipid peroxidation and an increase in catalase activity were observed with Noni by itself and the effect ameliorated changes observed with cisplatin when given in combination.

Radioprotective and Antioxidant Activity of Fractionated Extracts of Berries of Hippophae rhamnoides

Rakesh Kumar Sharma,Raman Chawla,Rajesh Arora,Shikha Singh,Ravinder Kumar Sagar,Raj Kumar,Ashok Sharma,Manju L. Gupta,Surender Singh,Jagdish Prasad,Haider A. Khan,Anand Swaroop,A.K. Sinha,A.K. Gupta,R 한국식품영양과학회 2007 Journal of medicinal food Vol.10 No.1

Plants are an abundant source of medicinal compounds, some of which are useful in combating free radical-1002 (flavonoid-poor fraction) of Hippophae rhamnoideswere screened on the basis of their reducing power in the aqueousphase. REC-1001 was selected for further study, since it exhibited 27.38 times higher antioxidant activity than REC-1002.REC-1001 also showed significant (P. .05) membrane protection potential at 50 .g/mL, which was attributed to its abilityto scavenge peroxyl radicals (64.82. 1.25% scavenging within 1,440 min). A significant (P. .05) difference of 67.02% infree radical scavenging activity at 1,000 ng/mL between REC-1001 and vitamin E demonstrated the extract fraction’s worthc-tion. Further, REC-1001 was found to be nontoxic up to 200 mg/kg of body weight. This research suggests that the REC-1001 fraction of H. rhamnoidesextract is a safe and effective antioxidant nutraceutical product.

Analysis of Various COVID-19 Prediction Techniques

Rakesh Kumar Arora,Manoj Kumar Gupta,Bhoopesh Singh Bhati 대한전자공학회 2021 IEIE Transactions on Smart Processing & Computing Vol.10 No.4

There is no precise treatment available for COVID-19, but treatment of a number of signs/symptoms is possible. This treatment is provided in accordance with the clinical position of the patient. Furthermore, supplementary care is proven as efficient for infected people. COVID-19 prediction techniques follow various steps, which include dataset collection, pre-processing, feature extraction, and classification. Numerous COVID-19 prediction techniques have been proposed in the literature. In this paper, various techniques are systematically reviewed on the basis outcomes, advantages, and disadvantages.

Interactions between Oxidative Stress, Lipid Profile and Antioxidants in Breast Cancer: A Case Control Study

Gupta, Rakesh Kumar,Patel, Amit Kumar,Kumari, Rajni,Chugh, Seema,Shrivastav, Chitrangada,Mehra, Siddharth,Sharma, Ajay Narayan Asian Pacific Journal of Cancer Prevention 2012 Asian Pacific journal of cancer prevention Vol.13 No.12

Oxidant/antioxidant balance has been suggested as an important factor for initiation and progression of cancer. The objective of this study was to determine changes in the levels of malondialdehyde (MDA), nitric oxide (NO), total cholesterol, triglycerides, LDL-cholesterol, HDL-cholesterol, total antioxidant capacity (TAC), glutathione peroxidase (GSH-Px), and superoxide dismutase (SOD) activities in serum samples of breast cancer patients (n=30) and healthy subjects (n=100). MDA and NO levels were found to be increased in breast cancer patients compared to the healthy subject group (p<0.05). Total cholesterol and triglycerides were elevated; and HDL-cholesterol level was found to be decreased in the cancer patients as compared to the healthy subjects (p<0.05). Compared to the healthy group, both serum TAC levels (p<0.001) and activity of SOD and GSH-Px (p=0.05) were found to be decreased in the breast cancer patients as compared to the healthy controls. Considering the data presented in this study, we suggest that free radicals induce lipid eroxidation and peroxidation of unsaturated fatty acid with decreased activity of enzymatic antioxidants in breast cancer.

Do the Health Claims Made for Morinda citrifolia (Noni) Harmonize with Current Scientific Knowledge and Evaluation of its Biological Effects

Gupta, Rakesh Kumar,Patel, Amit Kumar Asian Pacific Journal of Cancer Prevention 2013 Asian Pacific journal of cancer prevention Vol.14 No.8

Morinda citrifolia, also known as Great Morinda, Indian Mulberry, or Noni, is a plant belonging to the family Rubiaceae. A number of major chemical compounds have been identified in the leaves, roots, and fruits of the Noni plant. The fruit juice is in high demand in alternative medicine for different kinds for illnesses such as arthritis, diabetes, high blood pressure, muscle ached and pains, menstrual difficulties, headache, heart diseases, AIDS, gastric ulcer, sprains, mental depression, senility, poor digestion, arteriosclerosis, blood vessel problems, and drug addiction. Several studies have also demonstrated anti-inflammatory, antioxidant and apoptosis-inducing effects of Noni in various cancers. Based on a toxicological assessment, Noni juice was considered as safe. Though a large number of in vitro, and, to a certain extent, in vivo studies demonstrated a range of potentially beneficial effects, clinical data are essentially lacking. To what extent the findings from experimental pharmacological studies are of potential clinical relevance is not clear at present and this question needs to be explored in detail before an recommendations can be made.

Modeling and flow analysis of piezoelectric based micropump with various shapes of microneedle

Rakesh Kumar Haldkar,Vijay Kumar Gupta,Tanuja Sheorey 대한기계학회 2017 JOURNAL OF MECHANICAL SCIENCE AND TECHNOLOGY Vol.31 No.6

Micropumps have been investigated as drug delivery and disease diagnostic devices. Many of these micropumps have been designed,considering primarily, available micro fabrication technologies rather than appropriate pump performance analysis. Piezoelectric andsilicon based micro pumps are more popular as compared to other smart materials being explored. The microneedle is an integral part ofthese micropumps providing an interface between the drug reservoir and the patient’s body for extracting the blood for investigation. Blood collected in the pump chamber passes through the biosensor and gives the required investigation report. It is aimed to minimize thepain while the microneedle is inserted in the body without having any effect on the flow characteristics. Several factors affect the painwhile inserting the needle, out of which shape and size of the microneedle are two important parameters. In this study we have investigatedthe effect of shape of the microneedle on the flow inside the micropump. A micropump design is based on the required flow at thebiosensor point. All computations were carried out with water (Newtonian fluid) as the working fluid after carrying out a comparativeanalysis with human blood (non-Newtonian fluid). For the pentagonal shaped microneedle, the velocity at the top of the microneedle wasminimum, which is beneficial in that fluid should remain in contact with the sensor for longer time.

Residual gall bladder: An emerging disease after safe cholecystectomy

Vikas Gupta,Anil Kumar Sharma,Pradeep Kumar,Mantavya Gupta,Ajay Gulati,Saroj Kant Sinha,Rakesh Kochhar 한국간담췌외과학회 2019 Annals of hepato-biliary-pancreatic surgery Vol.23 No.4

Backgrounds/Aims: Residual gallbladder mucosa left after subtotal/partial cholecystectomy is prone to develop recurrent lithiasis and become symptomatic, which mandates surgical removal. Methods: we retrospectively evaluated the patients with residual gallbladder referred to us from January 2011 to December 2017. Based on MRCP we classified calot’s anatomy to – type I where cystic duct was seen and type II where sessile GB stump was seen. Results: 21 patients with median age 38 years and M:F::1:9.5, had undergone cholecystectomy (3 months-20 years) prior, presented with recurrent biliary pain. 3 had jaundice (CBD stone, Mirizzi and biliary stricture), 1 had pancreatitis and one had malignancy of the GB. Imaging revealed type I anatomy in 14 (67%) and type II in 7 (33%). All underwent completion cholecystectomy – open in 18 and laparoscopic in 3 (one converted to open). Additional procedure was required in 5 patients – CBD exploration in 2 (10%) and one each Hepatico-jejunostomy, extended cholecystectomy and splenectomy. Median hospital stay was 1 day. There was no mortality and 10% morbidity. One patient with malignancy died at 2 years, two died of unrelated cause, one developed incisional hernia and the remaining were well at a median follow up of 29 months. Conclusions: Residual GB lithiasis should be suspected if there are recurrent symptoms after cholecystectomy. MRCP based proposed classification can guide the management strategy. Completion cholecystectomy is curative.