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Nuclear lamins, a type V intermediate filament, are crucial components of the nuclear envelope's inner layer, maintaining nuclear integrity and mediating interactions between the nucleus and cytoplasm. Research on human iPSC-derived cells and animal models has demonstrated the importance of lamins in cardiac and skeletal muscle development and function. Mutations in lamins result in laminopathies, a group of diseases including muscular dystrophies, Hutchison–Gilford progeria syndrome, and cardiomyopathies with conduction defects. These conditions have been linked to disrupted autophagy, mTOR, Nrf2-Keap, and proteostasis signaling pathways, indicating complex interactions between the nucleus and cytoplasm. Despite progress in understanding these pathways, many questions remain about the mechanisms driving lamin-induced pathologies, leading to limited therapeutic options. This review examines the current literature on dysregulated pathways in cardiac and skeletal muscle laminopathies and explores potential therapeutic strategies for these conditions. [ABSTRACT FROM AUTHOR]

This study investigated the anticancer effect of the anti-parasitic drug artemisinin in combination with two redox modulators: vitamin C and pro-vitamin K3 (C/K3) The experiments were conducted on leukaemia cells Jurkat. Cells were treated with either artemisinin or C/K3 alone and with all three compounds. Cell proliferation and viability were analysed using trypan blue stating and automated cell counting. The results showed that artemisinin (>10 M) suppressed cell proliferation activity, but did not induce cell death up to 500 M. The drug demonstrated a clear cytostatic effect at concentra-tions 250 500 M – Jurkat cells did not proliferate, but were alive. The combination C/K3 (200:2, 300:3 M/M) applied alone did not affect cell proliferation and viability. Vitamins C/K3 in concen-tration ratio 500:5 (μM/M) decreased cell proliferation activity by ~10%. The triple combination artemisinin/C/K3 manifested synergistic anti-proliferative effects at all concentration ratios analysed. This synergistic effect increased with increasing C/K3 concentration. Based on literature data, it was assumed that the anti-proliferative effect of the triple combination was mediated by changes in the redox-homeostasis of cancer cells. The C/K3 redox system likely acted on cancer mitochondria and increased superoxide production and activation of pro-apoptotic signals, specific for cancer cells. On the other hand, artemisinin could generate hydroxyl radicals as a result of activation of Fenton reac-tions, depleting intracellular reducing equivalents. Both redox mechanisms lead to activation of signal pathways for induction of cancer cell death.

The role of reactive oxygen species (ROS) in myeloid development is well established. However, its aberrant generation alters hematopoiesis. Thus, a comprehensive understanding of events controlling ROS homeostasis forms the central focus of this study. We show that, in homeostasis, myeloid-like blood progenitor cells of the Drosophila larvae, which reside in a specialized hematopoietic organ termed the lymph gland, use TCA to generate ROS. However, excessive ROS production leads to lymph gland growth retardation. Therefore, to moderate blood progenitor ROS, Drosophila larvae rely on olfaction and its downstream systemic GABA. GABA internalization and its breakdown into succinate by progenitor cells activates pyruvate dehydrogenase kinase (PDK), which controls inhibitory phosphorylation of pyruvate dehydrogenase (PDH). PDH is the rate-limiting enzyme that connects pyruvate to the TCA cycle and to oxidative phosphorylation. Thus, GABA metabolism via PDK activation maintains TCA activity and blood progenitor ROS homeostasis, and supports normal lymph gland growth. Consequently, animals that fail to smell also fail to sustain TCA activity and ROS homeostasis, which leads to lymph gland growth retardation. Overall, this study describes the requirement of animal odor-sensing and GABA in myeloid ROS regulation and hematopoietic growth control. [ABSTRACT FROM AUTHOR]

This study investigated the anticancer effect of the anti-parasitic drug artemisinin in combination with two redox modulators: vitamin C and pro-vitamin K3 (C/K3) The experiments were conducted on leukaemia cells Jurkat. Cells were treated with either artemisinin or C/K3 alone and with all three compounds. Cell proliferation and viability were analysed using trypan blue stating and automated cell counting. The results showed that artemisinin (>10 μM) suppressed cell proliferation activity, but did not induce cell death up to 500 μM. The drug demonstrated a clear cytostatic effect at concentrations 250μ 500 μM - Jurkat cells did not proliferate, but were alive. The combination C/K3 (200:2, 300:3 μM/μM) applied alone did not affect cell proliferation and viability. Vitamins C/K3 in concentration ratio 500:5 (µM/μM) decreased cell proliferation activity by ~10%. The triple combination artemisinin/C/K3 manifested synergistic anti-proliferative effects at all concentration ratios analysed. This synergistic effect increased with increasing C/K3 concentration. Based on literature data, it was assumed that the anti-proliferative effect of the triple combination was mediated by changes in the redox-homeostasis of cancer cells. The C/K3 redox system likely acted on cancer mitochondria and increased superoxide production and activation of pro-apoptotic signals, specific for cancer cells. On the other hand, artemisinin could generate hydroxyl radicals as a result of activation of Fenton reactions, depleting intracellular reducing equivalents. Both redox mechanisms lead to activation of signal pathways for induction of cancer cell death. [ABSTRACT FROM AUTHOR]

Since prehistoric times Coccinia grandis has been used as traditional medicine for various diseases including diabetes, dyslipidemia, metabolic and digestive disorders. Although the rationality of efficacy as natural antioxidants with different bioactive compounds in Coccinia grandis against monosodium glutamate (MSG) induced hepato-cardiac damage remains to be disclosed. Six different solvent extracts of the leaves of Coccinia grandis were chosen to evaluate in vitro antioxidant and free radical (FR)-scavenging activity. Due to high antioxidant content and FR-scavenging property of ethanol extract of Coccinia grandis leaves (EECGL) and presence of different bioactive compounds in EECGL was further tested to evaluate in vivo hepato-protective and cardio-protective efficacy against MSG-induced anomalies. MSG-induced dyslipidemia, increased cell toxicity markers altered functional status and histopathological peculiarities of target organs were blunted by EECGL. Additionally, MSG incited increase level of interleukin (IL)-6, tumour necrosis factor (TNF)-α, IL-1β which activates nuclear factor kappa-B (NF-kB) guided inflammation via down regulation of IL-10; impaired redox-homeostasis subsequently promoted inflammation associated oxidative stress (OS) and increased vascular endothelial growth factor (VEGF) which provoked microvascular proliferation related cellular damage. On the contrary, increased lipid peroxidation and nitric oxide promotes reduced cell viability, deoxyribonucleic acid damage and apoptosis via activation of caspase 3. EECGL significantly reduced MSG-induced inflammation mediated OS and apoptosis via inhibition of pro-inflammatory factors and pro-apoptotic mediators to protect liver and heart. Therefore, it can be suggested that EECGL contributed competent scientific information to validate the demands for its use to treat MSG-induced hepato-cardiac OS mediated inflammation and apoptosis from natural origin. [ABSTRACT FROM AUTHOR]

Chilling injury is a physiological disorder affecting the quality of carambola fruit. In the present study, the effect of exogenous γ-aminobutyric acid (GABA) on CI development in carambola fruit during storage at 4°C for 15 days was investigated. The results showed that 2.5-mM GABA reduced CI index, maintained pericarp lightness, and decreased the electrolyte leakage (EL) and malondialdehyde content (MDA) while increased the superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activities. Endogenous GABA content was significantly higher in the treated fruit than in the control fruit during the whole storage. Besides, the treatment promoted the accumulation of proline and ascorbic acid (AsA) under chilling stress. Compared to the control, GABA-treated fruit exhibited a higher activity of phenylalanine ammonia-lyase (PAL) and total phenolic compounds, and a lower activity of polyphenol oxidase (PPO). In addition, the Safranin O/fast green staining revealed via microscopic images that the GABA treatment reduced the cell walls degradation of carambola fruit. Moreover, the results displayed a lower activity of phospholipase D (PLD) and lipoxygenase (LOX) enzymes, which coincided with a higher content of oleic acid (C18:1), linoleic acid (C18:2n6), and α-linolenic acid (C18:3n3) after 15 days of treatment, leading to the maintenance of the integrity and prevention of the membrane of the rapid softening of carambola fruit. The findings of the present work showed particularly new insights into the crosstalk between GABA and fatty acids. GABA might preserve the pericarp of carambola fruit by increasing the content of the unsaturated fatty acid (UFA) γ-linolenic acid and reducing the saturated fatty acid (SFA) such as caproic acid (C6:0), caprylic acid (C8:0), myristic acid (C14:0), and palmitic acid (C16:0) progressively. GABA can be used as an appropriate postharvest technology for improving the quality of carambola fruit during low-temperature storage.

The immunological and biochemical changes caused by pregnancy may uncover new aspects of immune tolerance, applicable in physiological and pathological contexts, and show up new therapeutic strategies for improving pregnancy outcomes. Isoimmune conflict in pregnancy is primarily related to the risk of pre-natal fetal death caused by massive hemolysis when incompatible with Rh and / or AB0 antigens. The objective: The objective: to evaluate the role of redox homeostasis in the formation of the immune response in isoimmune conflict during pregnancy. Results. The results obtained indicate the activation of T- and B-lymphocytes, which may be explained by the activation of cytokines IL-1, IL-6, IL-10. In pregnancy isoimmune conflict moderate metabolic acidosis is observed with a predominance of the lactic acid component and the depletion of buffer reserves. Conclusions. Isoimmune conflict leads to moderate formation of oxidative stress, that can be described as violation of redox-homeostasis, which in turn can be a consequence of cytotoxic reactions.

Abstract: The maintenance of the redox-homeostasis is an essential task of antioxidants. Reactive oxygen species (ROS) formed during oxidative stress can potentially damage the normal cellular functions and support pathological processes like atherosclerosis in vessels or malignant growth in other tissues, but also the aging process. However, recent findings link ROS also to cell survival and/or proliferation, which revolutionises the age-old dogmatic view of ROS being exclusively involved in cell damage and death. Low concentrations of hydrogenperoxide e.g. are involved in cell signaling and can activate mitogen-activated kinases (MAPK) to initiate cell growth. Nutritional antioxidants like vitamin C or E can promote endothelial cell growth, but can also inhibit growth of muscle cells, and influence MAPK. Thus, keeping the redox-homeostasis in a steady state especially in the context of tissue regeneration appears to be more important than previously known and seems to be a controlled synergistic action of antioxidants and ROS. The present review summarizes the properties and functions of ROS and nutritional antioxidants like the vitamins C and E, and polyphenols in redox-homeostasis. Their relevance in the treatment of various diseases is discussed in the context of a multitarget therapy with nutraceuticals and phytotherapeutic drugs. [Copyright &y& Elsevier]

Chilling injury is a physiological disorder affecting the quality of carambola fruit. In the present study, the effect of exogenous γ-aminobutyric acid (GABA) on CI development in carambola fruit during storage at 4°C for 15 days was investigated. The results showed that 2.5-mM GABA reduced CI index, maintained pericarp lightness, and decreased the electrolyte leakage (EL) and malondialdehyde content (MDA) while increased the superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) enzyme activities. Endogenous GABA content was significantly higher in the treated fruit than in the control fruit during the whole storage. Besides, the treatment promoted the accumulation of proline and ascorbic acid (AsA) under chilling stress. Compared to the control, GABA-treated fruit exhibited a higher activity of phenylalanine ammonia-lyase (PAL) and total phenolic compounds, and a lower activity of polyphenol oxidase (PPO). In addition, the Safranin O/fast green staining revealed via microscopic images that the GABA treatment reduced the cell walls degradation of carambola fruit. Moreover, the results displayed a lower activity of phospholipase D (PLD) and lipoxygenase (LOX) enzymes, which coincided with a higher content of oleic acid (C18:1), linoleic acid (C18:2n6), and α-linolenic acid (C18:3n3) after 15 days of treatment, leading to the maintenance of the integrity and prevention of the membrane of the rapid softening of carambola fruit. The findings of the present work showed particularly new insights into the crosstalk between GABA and fatty acids. GABA might preserve the pericarp of carambola fruit by increasing the content of the unsaturated fatty acid (UFA) γ-linolenic acid and reducing the saturated fatty acid (SFA) such as caproic acid (C6:0), caprylic acid (C8:0), myristic acid (C14:0), and palmitic acid (C16:0) progressively. GABA can be used as an appropriate postharvest technology for improving the quality of carambola fruit during low-temperature storage., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Ngaffo Mekontso, Duan, Cisse, Chen and Xu.)