Elucidation of underlying molecular mechanism of 5-Fluorouracil chemoresistance and its restoration using fish oil in experimental colon carcinoma

Molecular and Cellular Biochemistry - Latest strategies for cancer treatment primarily focus on the use of chemosensitizers to enhance therapeutic outcome. N-3 PUFAs have emerged as the strongest...     

Differential responses of antioxidant enzymes to aluminum toxicity in two rice (Oryza sativa L.) cultivars with marked presence and elevated activity of Fe SOD and enhanced activities of Mn SOD and catalase in aluminum tolerant cultivar

Seedlings of two Indica rice (Oryza sativa L.) cvs. HUR-105 and Vandana, differing in Al-tolerance were used to identify the key mechanisms involved in their differential behaviour towards Al toxicity. Cv. HUR-105 appeared to be Al sensitive by showing significant reduction (p ≤ 0.01) in root/shoot length, fresh weight, dry weight and water content in presence of 421 μM Al³⁺ in growth medium whereas cv. Vandana appeared to be fairly Al³⁺ tolerant. A conspicuous and significant reduction in dry weight of root and shoot was observed in Al sensitive cv. HUR-105 with 178 μM Al³⁺ treatment for 3 days. Al was readily taken up by the roots and transported to shoots in both the rice cultivars. Localization of absorbed Al was always greater in roots than in shoots. Our results of the production of reactive oxygen species (ROS) H₂O₂ and O₂ ^.? and activities of major antioxidant enzymes such as total superoxide dismutase (SOD), Cu/Zn SOD, Mn SOD, Fe SOD, catalase (CAT) and guaiacol peroxidase revealed Al induced higher oxidative stress, greater production of ROS and lesser capacity to scavenge ROS in cv. HUR-105 than Vandana. With Al treatment, higher oxidative stress was noted in shoots than in roots. Greatly enhanced activities of SOD (especially Fe and Mn SOD) and CAT in Al treated seedlings of cv. Vandana suggest the role of these enzymes in Al tolerance. Furthermore, a marked presence of Fe SOD in roots and shoots of the seedlings of Al tolerant cv. Vandana and its significant (p ≤ 0.01) increase in activity due to Al-treatment, appears to be the unique feature of this cultivar and indicates a vital role of Fe SOD in Al-tolerance in rice.     

Validation of Arsenic Resistance in <Emphasis Type="Italic">Bacillus cereus</Emphasis> Strain AG27 by Comparative Protein Modeling of <Emphasis Type="Italic">ars</Emphasis>C Gene Product

The ars gene system provides arsenic resistance to a variety of microorganisms and can be chromosomal or plasmid-borne. The arsC gene, which codes for an arsenate reductase is essential for arsenate resistance and transforms arsenate into arsenite, which is extruded from the cell. Therefore, arsC gene from Bacillus cereus strain AG27 isolated from soil was amplified, cloned and sequenced. The strain exhibited a minimum inhibitory concentration of 40 and 35 mM to sodium arsenate and sodium arsenite, respectively. Homology of the sequence, when compared with available database using BLASTn search showed that 300 bp amplicons obtained possess partial arsC gene sequence which codes for arsenate reductase, an enzyme involved in the reduction of arsenate to arsenite which is then effluxed out of the cell, thereby indicating the presence of efflux mechanism of resistance in strain. The efflux mechanism was further confirmed by atomic absorption spectroscopy and scanning electron microscopy studies. Moreover, three dimensional structure of modeled arsC from Bacillus cereus strain shares significant structural similarity with arsenate reductase protein of B.subtilis, consisting of, highly similar overall fold with single α/β domain containing a central four stranded, parallel, open-twisted β-sheet flanked by α-helices on both sides. The structure harbors the arsenic binding motif AB loop or P-loop that is highly conserved in arsenate reductase family.     

Impaired glucose homeostasis after a transient intermittent hypoxic exposure in neonatal rats

This initial report presents a neonatal rat model with exposure to a transient intermittent hypoxia (IH), which results in a persisting diabetes-like condition in the young rats. Twenty-five male pups were treated at postnatal day 1 with IH exposure by alternating the level of oxygen between 10.3% and 20.8% for 5 h. The treated animals were then maintained in normal ambient oxygen condition for 3 week and compared to age-matched controls. The IH treated animals exhibited a significantly higher fasting glucose level than the control animals (237.00 ± 19.66 mg/dL vs. 167.25 ± 2.95 mg/dL; P = 0.003); and a significantly lower insulin level than the control (807.0 ± 72.5 pg/mL vs. 1839.8 ± 377.6 pg/mL; P = 0.023). There was no difference in the mass or the number of insulin producing beta cells as well as no indicative of inflammatory changes; however, glucose tolerance tests showed a significantly disturbed glucose homeostasis. In addition, the amount of C-peptide secreted from the islets harvested from the IH animals were decreased significantly (from 914 pM in control to 809 pM in IH; P = 0.0006) as well. These observations demonstrate that the neonatal exposure to the IH regimen initiates the development of deregulation in glucose homeostasis without infiltration of inflammatory cells.     

Reactive oxygen species, ascorbate–glutathione pool, and enzymes of their metabolism in drought-sensitive and tolerant indica rice (Oryza sativa L.) seedlings subjected to progressing levels of water deficit

Water deficit for rice is a worldwide concern, and to produce drought-tolerant varieties, it is essential to elucidate molecular mechanisms associated with water deficit tolerance. In the present study, we investigated the differential responses of nonenzymatic antioxidants ascorbate (AsA), glutathione (GSH), and their redox pool as well as activity levels of enzymes of ascorbate–glutathione cycle in seedlings of drought-sensitive rice (Oryza sativa L.) cv. Malviya-36 and drought-tolerant cv. Brown Gora subjected to water deficit treatment of ?1.0 and ?2.1 MPa for 24–72 h using PEG-6000 in sand cultures. Water deficit caused increased production of reactive oxygen species such as O₂?^?, H₂O₂, and HO? in the tissues, and the level of production was higher in the sensitive than the tolerant cultivar. Water deficit caused reduction in AsA and GSH and decline in their redox ratios (AsA/DHA and GSH/GSSG) with lesser decline in tolerant than the sensitive seedlings. With progressive level of water deficit, the activities of monodehydroascorbate reductase, dehydroascorbate reductase, ascorbate peroxidase (APX), and glutathione transferase increased in the seedlings of both rice cultivars, but the increased activity levels were higher in the seedlings of drought-tolerant cv. Brown Gora compared to the sensitive cv. Malviya-36. Greater accumulation of proline was observed in stressed seedlings of tolerant than the sensitive cultivar. In-gel activity staining of APX revealed varying numbers of their isoforms and their differential expression in sensitive and tolerant seedlings under water deficit. Results suggest that an enhanced oxidative stress tolerance by a well-coordinated cellular redox state of ascorbate and glutathione in reduced forms and induction of antioxidant defense system by elevated activity levels of enzymes of ascorbate–glutathione cycle is associated with water deficit tolerance in rice.     

Draft Genome Sequence of an Extreme Haloarchaeon 3A1-DGR Isolated from a Saltern Crystallizer of the Little Rann of Kutch,India

Haloarchaea are predominant in the salt crystallizers of the Rann of Kutch when the concentration of salts approaches saturation levels. The obligate and extreme halophilic archaeon 3A1-DGR, isolated from a salt crystallizer pond of the Little Rann of Kutch, India, needs minimum of 10 % NaCl in the growth medium. To understand the mechanism(s) of osmotolerance and adaptation at extreme osmolarity, and to mine relevant gene(s), the genome of this haloarchaeon, 3A1-DGR, was sequenced. We report here, the 2.88 Mb draft genome sequence of the haloarchaeon 3A1-DGR, with G+C content of 68 % and the possible involvement of 43 genes in stress tolerance. Further studies of the genome of this haloarchaeon would be required to identify gene(s) that might be responsible for imparting extreme osmotolerance.     

Roles of ARF tumour suppressor protein in lung cancer: time to hit the nail on the head!

Owing to its poor prognosis, the World Health Organization (WHO) lists lung cancer on top of the list when it comes to growing mortality rates and incidence. Usually, there are two types of lung cancer, small-cell lung cancer (SCLC) and non-small-cell lung cancer (NSCLC), which also includes adenocarcinoma, squamous cell carcinoma and large cell carcinomas. ARF, also known in humans as p14ARF and in the mouse as p19ARF, is a nucleolar protein and a member of INK4, a family of cyclin-independent kinase inhibitors (CKI). These genes are clustered on chromosome number 9p21 within the locus of CDKN2A. NSCLC has reported the role of p14ARF as a potential target. p14ARF has a basic mechanism to inhibit mouse double minute 2 protein that exhibits inhibitory action on p53, a phosphoprotein tumour suppressor, thus playing a role in various tumour-related activities such as growth inhibition, DNA damage, autophagy, apoptosis, cell cycle arrest and others. Extensive cancer research is ongoing and updated reports regarding the role of ARF in lung cancer are available. This article summarizes the available lung cancer ARF data, its molecular mechanisms and its associated signalling pathways. Attempts have been made to show how p14ARF functions in different types of lung cancer providing a thought to look upon ARF as a new target for treating the debilitating condition of lung cancer.

     

Therapeutic opportunities of edible antiviral plants for COVID-19

Molecular and Cellular Biochemistry - The pandemic of Serious Acute Respiratory Syndrome Corona Virus-2 (SARS-CoV-2) that produces corona virus disease (COVID-19) has challenged the entire mankind...     

Oxidative stress, protein carbonylation, proteolysis and antioxidative defense system as a model for depicting water deficit tolerance in Indica rice seedlings

Water deficit is an important constraint to rice (Oryza sativa L.) productivity. The present study was undertaken to investigate whether the level of oxidative stress, carbonylation of proteins, proteolysis and status of antioxidative defense could serve as a model to distinguish water deficit tolerant and sensitive rice cultivars. When 10-day-grown seedlings of two rice cultivars, Malviya-36 (drought-sensitive) and Brown Gora (drought-tolerant) were subjected to ?1.0 and ?2.1 MPa water deficit treatments for 24–72 h with polyethylene glycol 6000 in the medium, a greater decline in the growth of the seedlings and levels of leaf water potential, relative water content, Chl a, Chl b, carotenoids and greater increase in leaf water loss were observed in the sensitive cultivar than the tolerant. Under similar level of water deficit seedlings of sensitive cultivar showed higher level of superoxide anion generation, H₂O₂, lipid peroxidation and proteolysis in roots as well as shoots compared to the tolerant. Drought-tolerant cultivar had higher constitutive level of antioxidative enzymes superoxide dismutase and catalase and the activities of these two enzymes alongwith of guaiacol peroxidase showed greater increase in this cultivar under water deficit compared to the sensitive. A significant decline in the level of protein thiol and a higher increase in protein carbonyls content, also confirmed by protein gel blot analysis with an antibody against 2,4-dinitrophenylhydrazine was observed in the seedlings of drought sensitive cv. Malviya-36 compared to the tolerant cv. Brown Gora when subjected to similar level of water deficit. Seedlings of drought sensitive cultivar, under water deficit, showed higher proteolytic activity, higher number of in-gel activity stained proteolytic bands and higher expression of oxidized proteins in roots compared to the tolerant cultivar. Results suggest that poor capacity of antioxidative enzymes could be, at least partly, correlated with water deficit sensitivity of sensitive cultivar and that higher activity of antioxidative enzymes superoxide dismutase, catalase, guaiacol peroxidase, low proteolytic activity, lower level of protein carbonyls and protein thiolation could serve as a model to depict water deficit tolerance in Indica rice seedlings.     

Effect of telmisartan on cardiovascular complications associated with streptozotocin diabetic rats

Angiotensin receptor blockers provide cardiovascular protection in heart failure patients. We have studied the effect of 8 weeks treatment with telmisartan (5 mg kg(-1) day(-1)) on cardiovascular complications associated with streptozotocin (STZ) diabetic rats. Wistar rats were made diabetic with STZ (45 mg kg(-1), iv). Various biochemical and cardiac parameters were measured at the end of 8 weeks. STZ produced hyperglycemia, hypoinsulinemia, hyperlipidemia, increased blood pressure, increased creatinine, cardiac enzyme and C-reactive protein (CRP) levels, reduction in heart rate and cardiac hypertrophy. Chronic treatment with telmisartan significantly (P < 0.05) prevented STZ induced hypertension and elevated fasting glucose level with simultaneous increase in serum insulin levels. It significantly (P < 0.05) reduced the elevated cholesterol, very low density lipoprotein (VLDL) and triglyceride levels in diabetic rats and increased the lower high density lipoprotein (HDL)-cholesterol levels. Further, telmisartan produced a significant (P < 0.05) reduction in the elevated creatinine levels, CRP and levels of other cardiac enzyme markers like Lactate de-hydrogenase and creatinine kinase of diabetic rats. STZ-induced bradycardia was also prevented by telmisartan treatment and it also produced beneficial effect by preventing cardiac hypertrophy as evident from left ventricular collagen levels, cardiac hypertrophy index and left ventricular hypertrophy index of diabetic rats. Our data suggest that telmisartan prevents not only the STZ-induced metabolic abnormalities, but also cardiovascular complications.