Microsatellite instability in north Indian colorectal cancer patients and its clinicopathological correlation.

BACKGROUND: Colorectal cancer (CRC) is the third most deadly and fourth most commonly diagnosed cancer in the world. Microsatellite instability (MSI) has been found associated with CRC, especially in prognostication. The present study has been carried out to find the genetic instability as demonstrated by MSI and its clinicopathological correlation in north Indian patients. METHODS: This prospective study was carried out on 103 CRC patients admitted for surgery between 2014 and 2018. MSI testing was done using 5-panel markers (BAT25, BAT26, D2S123, D5S346, and D17S250) by standard polymerase chain reaction (PCR) technique. The various clinicopathological factors were analysed to see their association with MSI status and also their effect on survival. Univariate analysis was performed by using the 2-tailed Student's t-test for continuous non-normally distributed variables, and categorical variables were compared using the chi-square test. Multivariate correlation analysis was performed by logistic regression test using SPSS version 16.0 (IBM Corporation, Armonk, NY, USA). Kaplan-Meier analysis was done to detect the patient's survival. A p-value < 0.05 was considered statistically significant. RESULTS: The frequency of MSI in patient population that we studied was 41.7% (43/103). MSI tumours were significantly associated with family history (OR = 5.63, p = 0.022*, 95% CI = 1.1-28.6) and tumour-infiltrating lymphocytes (TILS) (OR = 2.60, p = 0.023*, 95% CI = 1.1-6.0). The patients surviving longer (< 5 years vs > 5 years) were found significantly associated with MSI-high (MSI-H) (OR = 3.76, p = 0.029*, 95% CI = 1.2-4.5). CONCLUSION: Family history of cancer and presence of TILS were significantly associated with the presence of MSI-H tumours; also, patients surviving more than 5 years had more MSI-H phenotype.

Hydrogen sulphide and salicylic acid regulate antioxidant pathway and nutrient balance in mustard plants under cadmium stress.

Cadmium (Cd), a pervasive noxious heavy metal, is a key threat to agricultural system. It is rapidly translocated and has detrimental effects on plant growth and development. Hydrogen sulphide (H2 S) is emerging as a potential messenger molecule for modulating plant tolerance to Cd. Salicylic acid (SA), a phenolic signalling molecule, can alleviate Cd toxicity in plants. The present study investigated the mediatory role of H2 S (100 µM) and SA (0.5 mM), individually and in combination, in modulating antioxidant defence machinery and nutrient balance to impart Cd (50 µM) resistance to mustard. Accumulation of Cd resulted in oxidative stress (TBARS and H2 O2 ), mineral nutrient imbalance (N, P, K, Ca), decreased leaf gas exchange and PSII efficiency, ultimately reducing plant growth. Both H2 S and SA independently attenuated phytotoxic effects of Cd by triggering antioxidant systems, enhancing the nutrient pool, eventually leading to improved photosynthesis and biomass of mustard plants. The positive effects were more pronounced under combined application of H2 S and SA, indicating a synergistic relationship between these two signalling molecules in mitigating the detrimental effects of Cd on nutrient homeostasis and overall health of mustard, primarily by boosting antioxidant pathway. Our findings provide new insights into H2 S- and SA-induced protective mechanisms in mustard plants subjected to Cd stress and suggest their combined use as a feasible strategy to confer Cd tolerance.

Exogenous hydrogen sulphide alleviates copper stress impacts in Artemisia annua L.: Growth, antioxidant metabolism, glandular trichome development and artemisinin biosynthesis.

A supply of plant micronutrients (some of which are metals) is necessary to regulate many plant processes; their excess, however, can have detrimental consequences and can hamper plant growth, physiology and metabolism. Artemisia annua is an important crop plant used in the treatment of malaria. In this investigation, the physio-biochemical mechanisms involved in exogenous hydrogen sulphide-mediated (H2 S) alleviation of copper (Cu) stress in A. annua were assessed.. Two different levels of Cu (20, 40 mg·kg-1 ), one H2 S treatment (200 µm) and their combinations were introduced while one set of plants was retained as control. Results showed that the presence of excess Cu in the soil reduced growth and biomass, photosynthetic parameters, chlorophyll content and fluorescence, gas exchange parameters and induced antioxidant enzyme activity. Copper stress enhanced the production of thiobarbituric acid reactive substances (TBARS) and increased Cu content in both roots and shoots of affected plants. Exogenous application of H2 S restored the physio-biochemical characteristics of Cu-treated A. annua plants by reducing lipid peroxidation and enhancing the activity of antioxidant enzymes in Cu-stressed plants as compared with the controls. Hydrogen sulphide also reduced the Cu content in different plant parts, increased photosynthetic efficiency, trichome density, average area of trichomes and artemisinin content. Therefore, our results provide a comprehensive assessment of the defensive role of H2 S in Cu-stressed A. annua.

Interactive effects of hydrogen sulphide and silicon enhance drought and heat tolerance by modulating hormones, antioxidant defence enzymes and redox status in barley (Hordeum vulgare L.).

Recent changes in climate have reduced crop productivity throughout much of the world. Drought and heat stress, particularly in arid and semi-arid regions, have seriously affected barley production. This study explored the separate and interactive effects of silicon (Si) and hydrogen sulphide (H2 S) on plant growth and mitigation of the adverse effects of heat stress (DS) and drought stress (HS) in a barley pot experiment. The impacts of simultaneous DS + HS were more severe than individual stresses due to increased ROS production, malondialdehyde (MDA) content and higher electrolyte leakage (EL), thereby leading to reduced water, protein and photosynthetic pigment content. Exogenously applied Si and H2 S alleviated the DS-, HS- and DS + HS-induced effects on barley by reducing ROS production, MDA and EL. A single application of H2 S or Si + H2 S increased plant biomass under all stress conditions, which can be ascribed to higher Si accumulation in barley shoots. A single application of Si or H2 S significantly increased plant biomass. However, Si + H2 S was the most effective treatment for metabolite accumulation and elevating activity of antioxidant enzymes to prevent toxicity from oxidative stress. This treatment also modulated osmolyte content, enhanced antioxidant activity and regulated the stress signalling-related endogenous hormones, abscisic acid (ABA) and indole acetic acid (IAA). Exogenous treatments regulated endogenous H2 S and Si and resulted in higher tolerance to individual and combined drought and heat stress in barley.

Exogenous melatonin-mediated regulation of K+ /Na+ transport, H+ -ATPase activity and enzymatic antioxidative defence operate through endogenous hydrogen sulphide signalling in NaCl-stressed tomato seedling roots.

Melatonin (Mel) and hydrogen sulphide (H2 S) have emerged as potential regulators of plant metabolism during abiotic stress. Presence of excess NaCl in the soil is one of the main causes of reduced crop productivity worldwide. The present investigation examines the role of exogenous Mel and endogenous H2 S in tomato seedlings grown under NaCl stress. Effect of 30 µm Mel on endogenous synthesis of H2 S was examined in roots of NaCl-stressed (200 mm) tomato seedlings. Also, the impact of treatments on the oxidative stress markers, transport of K+ and Na+ , and activity of H+ -ATPase and antioxidant enzymes was assessed. Results show that NaCl-stressed seedlings supplemented with 30 µm Mel had increased levels of endogenous H2 S through enhanced L-cysteine desulfhydrase activity. Mel in association with H2 S overcame the deleterious effect of NaCl and induced retention of K+ that maintained a higher K+ /Na+ ratio. Use of plasma membrane inhibitors and an H2 S scavenger revealed that Mel-induced regulation of K+ /Na+ homeostasis in NaCl-stressed seedling roots operates through endogenous H2 S signalling. Synergistic effects of Mel and H2 S also reduced the generation of ROS and oxidative destruction through the enhanced activity of antioxidant enzymes. Thus, it is suggested that the protective function of Mel against NaCl stress operates through an endogenous H2 S-dependent pathway, wherein H+ -ATPase-energized secondary active transport regulates K+ /Na+ homeostasis.

Seed priming with gibberellic acid induces high salinity tolerance in Pisum sativum through antioxidants, secondary metabolites and up-regulation of antiporter genes.

Salinity is one of the major abiotic stresses that limit productivity of pulse crops all over the world. Seed priming with phytohormone(s) is one of the most promising, authentic and cost-effective methods to mitigate the deleterious effect of salinity. The study was conducted to investigate potential of seed priming with gibberellic acid (GA3 ) to cope up with the adverse effects of salinity (0, 100, 200 and 300 mm NaCl) in pea (Pisum sativum L.) seedlings. There were different responses to salinity, which induced oxidative stress, higher accumulation of Na+ in shoots and roots and inhibition of photosynthetic traits. However, seed priming with GA3 showed promising effects on physiological traits under salinity stress and alleviated the adverse effects of salinity by inducing the antioxidant system, proline production, total phenol and flavonoid content and regulating ion homeostasis, along with up-regulation of Na+ /H+ antiporters (SOS1 and NHX1). Plants adapt and prevent high salt accumulation by inducing expression of Na+ /H+  antiporter (SOS1 and NHX1) proteins that enhance Na+ sequestration. Thus, seed priming with GA3 is important in alleviation of high salinity stress and can be used as a criterion for developing salt-tolerant cultivars.

Phosphorus supplementation modulates nitric oxide biosynthesis and stabilizes the defence system to improve arsenic stress tolerance in mustard.

The interaction of mineral nutrients with metals/metalloids and signalling molecules is well known. In the present study, we investigated the effect of phosphorus (P) in mitigation of arsenic (As) stress in mustard (Brassica juncea L.). The study was conducted to investigate potential of 30 mg P·kg-1 soil P supplement (diammonium phosphate) to cope up with the adverse effects of As stress (24 mg As·kg-1 soil) in mustard plants Supplementation of P influenced nitric oxide (NO) generation, which up-regulated proline metabolism, ascorbate-glutathione system and glyoxalase system and alleviated the effects of on photosynthesis and growth. Arsenic stress generated ROS and methylglyoxal content was scavenged through P-mediated NO, and reduced As translocation from roots to leaves. The involvement of NO under P-mediated alleviation of As stress was substantiated with the use of cPTIO (NO biosynthesis inhibitor) and SNP (NO inducer). The reversal of P effects on photosynthesis under As stress with the use of cPTIO emphasized the role of P-mediated NO in mitigation of As stress and protection of photosynthesis The results suggested that P reversed As-induced oxidative stress by modulation of NO formation, which regulated antioxidant machinery. Thus, P-induced regulatory interaction between NO and reversal of As-induced oxidative stress for the protection of photosynthesis may be suggested for sustainable crops.

Effect of GA3 and 2,4-D foliar application on the anatomy of date palm (Phoenix dactylifera L.) seedling leaf.

Two concentrations (10-5M and 10-3M) of both GA3 and 2,4-D were used as foliar spray to evaluate the response of date palm (Phoenix dactylifera L.) cv. Khedri seedlings. They affected some of the anatomical characteristics of the first leaf emerging after the beginning of the spray. The high concentration of GA3 increased the size of the midrib and its vascular bundle numbers. Both low and high concentrations of 2,4-D inhibited the formation of the midrib. 2,4-D in both low and high concentrations decreased the number of vessels in both protoxylem and metaxylem and also decreased their diameters, where as GA3 in low and high concentrations have less effect on the number of vessels and its diameters. GA3 in high concentration increased the number of vascular bundles in 1mm long of the leaf blade, while 2,4-D in low and high concentrations decreased their numbers. 10-3M of 2,4-D increased the size and layers of special hypodermal cells.

An in vivo and in silico approach to elucidate the tocotrienol-mediated fortification against infection and inflammation induced alterations in antioxidant defense system.

BACKGROUND: Tocotrienol (Tocomin) are naturally occurring analogues of vitamin E family and has been reported to possess a potent free radical scavenging activity. In the present study we have initially investigated protective role of tocotrienol against infection and inflammation induced alterations in tissues antioxidant defense system, as well as speculated, via in silico docking studies, that tocotrienol can act by directly binding to antioxidant enzymes. MATERIALS AND METHODS: Syrian hamsters were injected with bacterial lipopolysaccharide (LPS, 200 microg), zymosan (20 mg), or turpentine (0.5 ml) to mimic acute infection, acute systemic inflammation, and acute localized inflammation, respectively, which are responsible for the generation of plenty of free radicals that causes oxidative stress. Tocomin (10 mg) was administered daily for 10 days before and 12 h after lipopolysaccharides (LPS) or 24 h after turpentine or zymosan injection. Molecular docking studies were performed using Autodock 4.0. RESULTS: Our results show a significant decrease in the activities of antiperoxidative enzymes, glutathione reductase (GR), glutathione peroxidase (GPx), catalase (CAT), superoxide dismutase (SOD), glutathione-s-transferase (GST), as well as reduced glutathione (GSH), in liver and kidney of LPS, turpentine or zymosan stressed hamsters. Feeding of 10 mg Tocomin to stressed hamsters was quite effective in reversing/normalizing the altered levels of enzymatic and nonenzymatic antioxidants in liver and kidney. In order to explore the interaction between tocotrienol and antioxidant enzymes a molecular docking study was performed. The results showed good interaction in term of binding energy and inhibition constant in the following order GR > CAT > SOD > GST > GPx. CONCLUSION: Our in vivo and in silico results for the first time indicate that tocotrienol significantly alleviate the condition of oxidative stress not only by its potent free radical scavenging properties but also may be by interacting directly and strongly with antioxidant enzymes as proved by molecular docking simulations.

Experimental confirmation of Kelvin's equilibria.

We experimentally corroborate the core analytical deductions of Thomson's 124-year-old theorem, vis-à-vis the stability of a ring of N vortices. Observations made in water vortices produced inside a cylinder via a revolving disk confirm that the regular N-gons are stable for Nor=8. The N