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Therapeutic Methods and Therapies TCIM
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1.
Science ; 380(6649): eabn9257, 2023 06 09.
Article in English | MEDLINE | ID: mdl-37289866

ABSTRACT

Aging is associated with changes in circulating levels of various molecules, some of which remain undefined. We find that concentrations of circulating taurine decline with aging in mice, monkeys, and humans. A reversal of this decline through taurine supplementation increased the health span (the period of healthy living) and life span in mice and health span in monkeys. Mechanistically, taurine reduced cellular senescence, protected against telomerase deficiency, suppressed mitochondrial dysfunction, decreased DNA damage, and attenuated inflammaging. In humans, lower taurine concentrations correlated with several age-related diseases and taurine concentrations increased after acute endurance exercise. Thus, taurine deficiency may be a driver of aging because its reversal increases health span in worms, rodents, and primates and life span in worms and rodents. Clinical trials in humans seem warranted to test whether taurine deficiency might drive aging in humans.


Subject(s)
Aging , Taurine , Animals , Humans , Mice , Aging/blood , Aging/drug effects , Aging/metabolism , Cellular Senescence , Haplorhini , Longevity/drug effects , Longevity/physiology , Taurine/blood , Taurine/deficiency , Taurine/pharmacology , Dietary Supplements , DNA Damage/drug effects , Telomerase/metabolism
2.
Plant Mol Biol ; 106(1-2): 85-108, 2021 May.
Article in English | MEDLINE | ID: mdl-33629224

ABSTRACT

KEY MESSAGE: Overexpression of StCaM2 in tobacco promotes plant growth and confers increased salinity and drought tolerance by enhancing the photosynthetic efficiency, ROS scavenging, and recovery from membrane injury. Calmodulins (CaMs) are important Ca2+ sensors that interact with effector proteins and drive a network of signal transduction pathways involved in regulating the growth and developmental pattern of plants under stress. Herein, using in silico analysis, we identified 17 CaM isoforms (StCaM) in potato. Expression profiling revealed different temporal and spatial expression patterns of these genes, which were modulated under abiotic stress. Among the identified StCaM genes, StCaM2 was found to have the largest number of abiotic stress responsive promoter elements. In addition, StCaM2 was upregulated in response to some of the selected abiotic stress in potato tissues. Overexpression of StCaM2 in transgenic tobacco plants enhanced their tolerance to salinity and drought stress. Accumulation of reactive oxygen species was remarkably decreased in transgenic lines compared to that in wild type plants. Chlorophyll a fluorescence analysis suggested better performance of photosystem II in transgenic plants under stress compared to that in wild type plants. The increase in salinity stress tolerance in StCaM2-overexpressing plants was also associated with a favorable K+/Na+ ratio. The enhanced tolerance to abiotic stresses correlated with the increase in the activities of anti-oxidative enzymes in transgenic tobacco plants. Overall, our results suggest that StCaM2 can be a novel candidate for conferring salt and drought tolerance in plants.


Subject(s)
Calcium-Binding Proteins/metabolism , Droughts , Nicotiana/genetics , Nicotiana/physiology , Plant Proteins/metabolism , Salinity , Solanum tuberosum/metabolism , Stress, Physiological , Antioxidants/metabolism , Calcium-Binding Proteins/genetics , Calmodulin/genetics , Calmodulin/metabolism , Gene Expression Profiling , Gene Expression Regulation, Plant/drug effects , Genome, Plant , Germination/drug effects , Germination/genetics , Ions , Membranes , Photosynthesis/drug effects , Plant Growth Regulators/pharmacology , Plant Proteins/genetics , Plants, Genetically Modified , Proline/metabolism , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reactive Oxygen Species/metabolism , Regulatory Sequences, Nucleic Acid/genetics , Seedlings/drug effects , Seedlings/genetics , Seedlings/growth & development , Stress, Physiological/drug effects , Stress, Physiological/genetics , Nicotiana/enzymology , Nicotiana/growth & development , Transcription Factors/metabolism , Water/metabolism
3.
Curr Protein Pept Sci ; 21(9): 899-915, 2020.
Article in English | MEDLINE | ID: mdl-32039678

ABSTRACT

The non-enzymatic interaction of sugar and protein resulting in the formation of advanced glycation end products responsible for cell signaling alterations ultimately leads to the human chronic disorders such as diabetes mellitus, cardiovascular diseases, cancer, etc. Studies suggest that AGEs upon interaction with receptors for advanced glycation end products (RAGE) result in the production of pro-inflammatory molecules and free radicals that exert altered gene expression effect. To date, many studies unveiled the potent role of synthetic and natural agents in inhibiting the glycation reaction at a lesser or greater extent. This review focuses on the hazards of glycation reaction and its inhibition by natural antioxidants, including polyphenols.


Subject(s)
Antioxidants/therapeutic use , Cardiovascular Diseases/drug therapy , Diabetes Mellitus, Type 2/drug therapy , Glycation End Products, Advanced/antagonists & inhibitors , Neoplasms/drug therapy , Polyphenols/therapeutic use , Antigens, Neoplasm/genetics , Antigens, Neoplasm/metabolism , Cardiovascular Diseases/genetics , Cardiovascular Diseases/metabolism , Cardiovascular Diseases/pathology , Deoxyglucose/analogs & derivatives , Deoxyglucose/metabolism , Diabetes Mellitus, Type 2/genetics , Diabetes Mellitus, Type 2/metabolism , Diabetes Mellitus, Type 2/pathology , Gene Expression Regulation , Glycation End Products, Advanced/genetics , Glycation End Products, Advanced/metabolism , Glyoxal/metabolism , Humans , Lactoylglutathione Lyase/genetics , Lactoylglutathione Lyase/metabolism , Mitogen-Activated Protein Kinases/genetics , Mitogen-Activated Protein Kinases/metabolism , NF-kappa B/genetics , NF-kappa B/metabolism , Neoplasms/genetics , Neoplasms/metabolism , Neoplasms/pathology , Oxidative Stress , Plant Extracts/chemistry , Protein Carbonylation , Pyruvaldehyde/metabolism , Signal Transduction
4.
Microb Pathog ; 140: 103933, 2020 Mar.
Article in English | MEDLINE | ID: mdl-31862392

ABSTRACT

Lichens are composite organisms, comprising of a fungus (mycobiont) and a blue-green alga (photobiont). Along with the mycobiont, numerous non-obligate microfungi live in lichen thalli. These microfungi are called endolichenic fungi (ELF). In recent years, the ELF are emerging as promising natural sources because of their capability to exert unique drug molecules. The current study aimed to isolate the ELF from the lichen, Usnea longissima Ach., to control of biofilm formation and quorum sensing phenomenon in Pseudomonas aeruginosa PAO1, an opportunistic multidrug resistance pathogen that uses quorum sensing network to produce an array of pathogenic agents. Therefore, inhibiting quorum sensing to manage the infection caused by PAO1 could be the paramount alternative approach to conventional antibiotics. The isolated ELF was identified by amplifying the long subunit region of the fungal genome. The extracted metabolites of ELF (MELE) using the acetone solvent was further investigated for anti-quorum sensing activity using the biomarker strain Chromobacterium violaceum 12472 which exerts violacein pigment via the AHL mediated quorum sensing signalling. Moreover, the effect of MELE was also evaluated on the production of virulence factors and biofilm formation of P. aeruginosa PAO1. The molecular identification revealed that ELF (accession number MN171299) exhibited 100% similarity with Aspergillus quandricinctus strain CBS 135.52. The MELE showed significant anti-quorum sensing activity at the concentration of 4 mg/mL without affecting the bacterial cell viability of P. aeruginosa PAO1. The MELE diminished the production of virulence factors, including pyocyanin, protease, elastase, rhamnolipids, and extracellular polysaccharides of P. aeruginosa PAO1 in a concentration-dependent manner. The MELE also disturbed biofilm formation of P. aeruginosa PAO1. The 3-D analysis of biofilm architecture showed that the thickness and surface area covered by microcolonies was decreased as the concentration of MELE was increased. The GC-MS analysis of MELE exhibited that organic acids and fatty acids are major constituents of the MELE. The present study reports first time that the ELF, A. quandricinctus possesses potential to inhibit quorum sensing and biofilm formation of P. aeruginosa and can be further exploited for hospital and healthcare facilities.


Subject(s)
Anti-Bacterial Agents/isolation & purification , Aspergillus , Pseudomonas aeruginosa/drug effects , Quorum Sensing/drug effects , Usnea , Anti-Bacterial Agents/metabolism , Anti-Bacterial Agents/pharmacology , Aspergillus/isolation & purification , Aspergillus/metabolism , Biofilms/drug effects , Chromobacterium/drug effects , Chromobacterium/metabolism , Indoles/metabolism , Lichens/microbiology , Pyocyanine/metabolism , Virulence Factors/metabolism
5.
Transgenic Res ; 22(4): 813-22, 2013 Aug.
Article in English | MEDLINE | ID: mdl-23378163

ABSTRACT

Alpha (α)-tocopherol is the most biologically active and preferentially retained form of vitamin E in the human body and is known for its antioxidant and gene regulatory functions. Its increased intake is implicated in protection against diseases that involve an oxidative stress component. We have evaluated the chemopreventive potential of a diet supplemented with natural α-tocopherol-enriched transgenic (TR) Brassica juncea seeds. The modulation of phase I and phase II xenobiotic metabolism and of antioxidative enzymes was compared in the livers of mice fed on a control diet or on a diet supplemented with 2, 4, and 6 % (w/w) of wild-type (WT) or TR seeds. A dose-dependent increase in the specific activities of these enzymes was observed in those animals fed on diet supplemented with TR seeds. In comparison, an increase in the specific activities of antioxidative enzymes was substantial only at higher doses of WT seeds. Consequently, oxidative stress measured in terms of lipid peroxidation and lactate dehydrogenase activity was found to be lower in the case of mice fed with the supplemented diet. However, the chemopreventive potential of TR seeds was more pronounced than that of WT seeds. This study demonstrates the feasibility of fortifying diets with natural α-tocopherol for chemopreventive benefits by means of transgenic manipulation of a commonly used oilseed crop.


Subject(s)
Antioxidants/metabolism , Liver/drug effects , Mustard Plant/genetics , Plants, Genetically Modified/metabolism , Animals , Diet , Humans , Lipid Peroxidation/drug effects , Liver/metabolism , Mice , Oxidative Stress/drug effects , Xenobiotics/metabolism , alpha-Tocopherol/administration & dosage
6.
Transgenic Res ; 16(1): 109-13, 2007 Feb.
Article in English | MEDLINE | ID: mdl-17103027

ABSTRACT

Alpha-tocopherol, the most biologically active form of vitamin E, is implicated in decreasing the risk of several types of cancers, coronary heart disease and a number of degenerative human conditions, when taken in excess of the recommended daily allowance. Natural alpha-tocopherol has twice the bioavailability of the synthetic isomer. This study describes a successful attempt at fortifying human diets with natural alpha-tocopherol by taking recourse to genetic engineering of an important oilseed crop, Brassica juncea. Gamma-tocopherol methyl transferase cDNA from Arabidopsis thaliana, coding for the enzyme catalysing the conversion of the large gamma-tocopherol pool to alpha-tocopherol, was overexpressed in B. juncea plants. The successful integration of the transgene was confirmed by PCR and Southern blot analysis, while the enhanced transcript level was evident in the northern blot analysis. HPLC analysis of the seeds of the T1 transgenic lines showed a shift in tocopherol profile with the highest over-expressors having alpha-tocopherol levels as high as sixfold over the non-transgenic controls. This study discusses the production of a transgenic oilseed crop with high alpha-tocopherol levels, which can provide a feasible, innocuous, and inexpensive way of taking the beneficial effects of high alpha-tocopherol intake to the masses.


Subject(s)
Methyltransferases/genetics , Mustard Plant/genetics , Mustard Plant/metabolism , alpha-Tocopherol/metabolism , Antioxidants/metabolism , Arabidopsis/enzymology , Arabidopsis/genetics , DNA, Plant/genetics , Diet , Food, Fortified , Genes, Plant , Genetic Engineering , Humans , Plants, Genetically Modified
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