ABSTRACT
Objective: In this study, the combined effect of two stressors, namely, electromagnetic fields (EMFs) from mobile phones and fructose consumption, on hypothalamic and hepatic master metabolic regulators of the AMPK/SIRT1-UCP2/FOXO1 pathway were elucidated to delineate the underlying molecular mechanisms of insulin resistance. Methods: Weaned Wistar rats (28 days old) were divided into 4 groups: Normal, Exposure Only (ExpO), Fructose Only (FruO), and Exposure and Fructose (EF). Each group was provided standard laboratory chow ad libitum for 8 weeks . Additionally, the control groups, namely, the Normal and FruO groups, had unrestricted access to drinking water and fructose solution (15%), respectively. Furthermore, the respective treatment groups, namely, the ExpO and EF groups, received EMF exposure (1,760 MHz, 2 h/day x 8 weeks). In early adulthood, mitochondrial function, insulin receptor signaling, and oxidative stress signals in hypothalamic and hepatic tissues were assessed using western blotting and biochemical analysis. Result: In the hypothalamic tissue of EF, SIRT1, FOXO 1, p-PI3K, p-AKT, Complex III, UCP2, MnSOD, and catalase expressions and OXPHOS and GSH activities were significantly decreased ( P < 0.05) compared to the Normal, ExpO, and FruO groups. In hepatic tissue of EF, the p-AMPKα, SIRT1, FOXO1, IRS1, p-PI3K, Complex I, II, III, IV, V, UCP2, and MnSOD expressions and the activity of OXPHOS, SOD, catalase, and GSH were significantly reduced compared to the Normal group ( P < 0.05). Conclusion: The findings suggest that the combination of EMF exposure and fructose consumption during childhood and adolescence in Wistar rats disrupts the closely interlinked and multi-regulated crosstalk of insulin receptor signals, mitochondrial OXPHOS, and the antioxidant defense system in the hypothalamus and liver.
Subject(s)
Cell Phone , Fructose , Humans , Rats , Animals , Adult , Rats, Wistar , Fructose/metabolism , Catalase , Receptor, Insulin/metabolism , AMP-Activated Protein Kinases/metabolism , Electromagnetic Fields/adverse effects , Sirtuin 1/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Forkhead Box Protein O1/metabolism , Uncoupling Protein 2ABSTRACT
Complete and balanced nutrition has always been the first line of plant defense due to the direct involvement of mineral elements in plant protection. Mineral elements affect plant health directly by modulating the activity of redox enzymes or improving the plant vigor indirectly by altering root exudates, and changing microflora population dynamics, rhizosphere soil nutrient content, pH fluctuation, lignin deposition, and phytoalexin biosynthesis. Nitrogen (N) is one of the most important macronutrients having a significant impact on the host-pathogen axis. N negatively affects the plant's physical defense along with the production of antimicrobial compounds, but it significantly alleviates defense-related enzyme levels that can eventually assist in systemic resistance. Potassium (K) is an essential plant nutrient, when it is present in adequate concentration, it can certainly increase the plant's polyphenolic concentrations, which play a critical role in the defense mechanism. Although no distinguished role of phosphorus (P) is observed in plant disease resistance, a high P content may increase the plant's susceptibility toward the invader. Manganese (Mn) is one of the most important micronutrients, which have a vital effect on photosynthesis, lignin biosynthesis, and other plant metabolic functions. Zinc (Zn) is a part of enzymes that are involved in auxin synthesis, infectivity, phytotoxin, and mycotoxin production in pathogenic microorganisms. Similarly, many other nutrients also have variable effects on enhancing or decreasing the host susceptibility toward disease onset and progression, thereby making integrative plant nutrition an indispensable component of sustainable agriculture. However, there are still many factors influencing the triple interaction of host-pathogen-mineral elements, which are not yet unraveled. Thereby, the present review has summarized the recent progress regarding the use of macro- and micronutrients in sustainable agriculture and their role in plant disease resistance.
ABSTRACT
The bacterial canker disease of tomato caused by Clavibacter michiganensis subsp. michiganensis (Cmm) has been reported to adversely affect the tomato cultivation in the NE hilly regions of India. Defense inducers such as salicylic acid (SA), isonicotinic acid (INA), benzothiadiazole (BTH) and lysozyme were used as prophylactic and curative sprays at different concentrations to test their efficacy in inducing resistance in tomato plants against Cmm under protected conditions. The induced resistance was studied through the alteration in the activities of oxidative stress marker enzymes (PAL, PO, PPO, TPC and PR-2 protein), hydrogen peroxide formation in leaf tissues and lignin accumulation in stem tissues, as well as through the reduction in disease severity under glasshouse conditions. The results of the present study revealed that the enzymatic activity, hydrogen peroxide formation and lignin production were significantly higher in the BTH (500 ppm)-treated leaves than in those observed in the control. The lowest disease incidence was recorded when BTH was applied as a prophylactic spray (27.88%) in comparison to being applied as a curative spray (53.62%), thereby suggesting that a defense inducer, BTH, shows antibacterial activity against Cmm, reduces disease incidence severity and induces defense responses in the tomato plant.
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Purpose: Fructose is highly lipogenic, and its unhindered ingestion by children and adolescents is understood to induce hypertriglyceridemia and non-alcoholic fatty liver disease (ped-NAFLD) that is till date managed symptomatically or surgically. The aim of the present study was to investigate the potential of hydroethanolic extract of leaves of Guava (PG-HM) to suppress the alterations in the hepatic molecular signals due to unrestricted fructose (15%) drinking by growing rats. Methods: Weaned rats (4 weeks old) in control groups had ad libitum access to fructose drinking solution (15%) for four (4FDR) or eight (8FDR) weeks, ie, till puberty or early adulthood, respectively, while treatment groups (4PGR, 8PGR) additionally received PG-HM (500 mg/kg, po). Results: The PG-HM suppressed ped-NAFLD through hepatic signalling pathways of 1) leptin-insulin (Akt/FOX-O1/SREBP-1c), 2) hypoxia-inflammation (HIF-1É/VEGF, TNF-É), 3) mitochondrial function (complexes I-V), 4) oxidative stress (MDA, GSH, SOD) and 5) glycolysis/gluconeogenesis/de novo lipogenesis (hexokinase, phosphofructokinase, ketohexokinase, aldehyde dehydrogenase). Parri passu, the insulin sensitizing effect of PG-HM and its ethyl acetate fraction (PG-EA) was elucidated using HepG2 cells grown in media enhanced with fructose. Further, in murine hepatocytes cultured in fructose-rich media, PG-HM (35 µg mL-1) outperformed Pioglitazone (15 µM) and Metformin (5 mM), to suppress hepatic insulin resistance. Conclusion: This study established that hydroethanolic extract of leaves of Guava (PG-HM) has potential to suppress hepatic metabolic alteration for the management of the pediatric NAFLD.
ABSTRACT
INTRODUCTION: Cerebral creatine deficiency syndromes (CCDS) are a group of potentially treatable neurometabolic disorders. The clinical, genetic profile and follow up outcome of Indian CCDS patients is presented. MATERIALS AND METHODS: This was a retrospective cohort of CCDS patients seen over six-years. Diagnosis was based either on low creatine peak on proton magnetic resonance spectroscopy (MRS) and/or genetic evaluation. RESULTS: Thirteen patients were eligible [8 creatine transporter deficiency (CTD), 4 guanidinoacetate methyltransferase (GAMT) deficiency and 1 could not be classified]. The mean (±SD) age at diagnosis was 7.2(±5.0) years. Clinical manifestations included intellectual disability (ID) with significant expressive speech delay in all. Most had significant behavior issues (8/13) and/or autism (8/13). All had history of convulsive seizures (11/13 had epilepsy; 2 patients only had febrile seizures) and 2/13 had movement disorder. Constipation was the commonest non-neurological manifestation (5/13 patients). Cranial MRI was normal in all CTD patients but showed globus pallidus hyperintensity in all four with GAMT deficiency. MRS performed in 11/13 patients, revealed abnormally low creatine peak. A causative genetic variant (novel mutation in nine) was identified in 12 patients. Three GAMT deficiency and one CTD patient reported neurodevelopmental improvement and good seizure control after creatine supplementation. CONCLUSION: Intellectual disability, disproportionate speech delay, autism, and epilepsy, were common in our CCDS patients. A normal structural neuroimaging with easily controlled febrile and/or afebrile seizures differentiated CTD from GAMT deficiency patients who had abnormal neuroimaging and often difficult to control epilepsy and movement disorder.
Subject(s)
Brain Diseases, Metabolic, Inborn/diagnosis , Creatine/deficiency , Guanidinoacetate N-Methyltransferase/deficiency , Language Development Disorders/diagnosis , Mental Retardation, X-Linked/diagnosis , Movement Disorders/congenital , Neurodevelopmental Disorders/diagnosis , Plasma Membrane Neurotransmitter Transport Proteins/deficiency , Brain Diseases, Metabolic, Inborn/complications , Brain Diseases, Metabolic, Inborn/genetics , Brain Diseases, Metabolic, Inborn/physiopathology , Child , Child, Preschool , Creatine/genetics , Female , Follow-Up Studies , Guanidinoacetate N-Methyltransferase/genetics , Humans , India , Language Development Disorders/complications , Language Development Disorders/genetics , Language Development Disorders/physiopathology , Male , Mental Retardation, X-Linked/complications , Mental Retardation, X-Linked/genetics , Mental Retardation, X-Linked/physiopathology , Movement Disorders/complications , Movement Disorders/diagnosis , Movement Disorders/genetics , Movement Disorders/physiopathology , Neurodevelopmental Disorders/etiology , Neurodevelopmental Disorders/genetics , Neurodevelopmental Disorders/physiopathology , Plasma Membrane Neurotransmitter Transport Proteins/genetics , Retrospective StudiesABSTRACT
The present-day children-adolescents ubiquitously use the mobile phones and unrestrictedly consume fructose-laden diet. Unfortunately, a rise in the incidence of insulin resistance and fatty liver syndrome in young adults has also been recorded. To delineate a possible correlate, the effect of exposure to electromagnetic field (EMF) from the mobile phone and unrestricted fructose intake during pre-, peri-, and post-pubertal stages of development on orexigenic and anorexigenic signals arising from the hypothalamus and liver of rats is investigated here. The study design included four arms, i.e., "Normal", "Exposure Only (ExpO)", "Fructose Only (FruO)", and "Exposure with Fructose (EF)", wherein weaned rats received either "normal chow and drinking water" or "normal chow and fructose (15%) drinking solution" in presence and absence of EMF exposure (2 h/day) for 8 weeks. The results indicate that the total calories consumed by the EF were higher by early adulthood than normal, possibly under the influence of the raised levels of the orexigenic hormone, i.e., ghrelin, and it reflected as raised rate of weight gain. At early adulthood, the EF recorded mitigated response and sensitivity of insulin. Despite EF being a "fed-state", both centrally and peripherally, the glycolysis was restrained, but the gluconeogenesis was raised. Additionally, the altered lipid profile and the glycogen levels indicate that the EF developed fatty liver. The energy homeostasis of the EF was compromised as evidenced by (a) reduced expression of the glucosensors-GLUT2 and glucokinase in the hypothalamus and liver and (b) reduced expression of the cellular energy regulator-AMPK, orexigenic peptide-NPY, and anorexigenic peptide-POMC in the hypothalamus. Taken together, the present study evidences that the exposure to EMFfrom the mobile phone and unrestricted fructose intake during childhood-adolescence impairs the central and peripheral pathways that mediate the glucosensing, glucoregulation, feeding, and satiety behavior by early adulthood.
Subject(s)
Cell Phone , Fructose , Animals , Electromagnetic Fields , Homeostasis , Hypothalamus , Liver , RatsABSTRACT
INTRODUCTION: In a developing country like India, a proportionately higher number of elderly people live in the rural areas and many of them are financially challenged. Hospitalization and consequent cost thereto pose a heavy burden especially for the elderly. OBJECTIVE: Among elderly in.patients at a tertiary care rural hospital to estimate the average number of episodes of hospitalizations, duration of stay in the hospital, and the direct and indirect costs associated with hospitalizations with 1 year as a reference period. MATERIALS AND METHODS: A structured pre.tested questionnaire was used to capture the details regarding hospitalizations and the costs involved and also the hospital records were verified for the current hospital admission to finally arrive at the direct and indirect costs calculations. Quantitative details like age, episodes of hospitalization in the last 1 year, duration of hospitalization, hospitalization costs, etc., were summarized as median (inter.quartile range [IQR]). Costing analyses were noted separately as direct, indirect, and total costs and expressed in Indian National Rupees (INR). RESULTS: The total number of episodes of hospitalization among the 150 study participants was 204 with a mean of 1.36 episodes per person in 1-year duration. The average total cost per episode of hospitalization was found to be INR 11,249 while the average total cost per person per day was INR 1,670.30. The median (IQR) direct and indirect costs were INR 6,222 (3,060-12,670) and INR 690 (200-700), respectively. CONCLUSION: Duration, as well as cost of hospitalization, has been found to be more among females in most age groups among elderly in.patients.