Hereditary Spherocytosis with Mitochondrial Retention, Increased Oxidative Stress, and Alterations to Bioactive Membrane Lipids.

The clinical course for Hereditary Spherocytosis (HS) patients is highly varied, even within families with identical driving mutations. Here, we describe four siblings with HS attributed to an unreported SPTB mutation. All patients displayed an increased fraction of mitochondria-positive erythrocytes. This was associated with increased reactive oxygen species (ROS) generation and alteration to alterations to bioactive membrane lipids associated with oxidant stress. Given the early promise for mitophagy-inducing agents in sickle cell disease and ready availability of antioxidants, this concept warrants continued exploration as a disease-modifying factor and a potential target for therapy.

Maternal supplementation of high-value PUFA-Rich Isochrysis sp. biomass prevents monosodium glutamate-induced neurotoxicity in first-generation Wistar rats.

Prenatal supplementation of high-value PUFA (HVPUFA) is essential for adequate brain development in infants. As marine microalgal derived omega-3 fatty acids are considered an alternative source of fish oil, their neuroprotective role on monosodium glutamate (MSG)-induced neurotoxicity, bioavailability, and disease prevention in first-generation (F1) animals need to be explored at molecular level. This study tested the long term supplementation of microalgal derived ω-3 PUFAs from parent rats to its offspring rats and studied the neuroprotective role in monosodium glutamate (MSG)-induced neurotoxicity in F1 rats. The parent animals were divided into three groups: control, microalgal-administered group (5.7 mg of EPA and 1.4 mg of DHA/kg BW from Isochrysis sp.), and fish oil-administered group (4.2 mg of EPA and 2.9 mg of DHA/kg BW derived from fish oil) (FG) and continued up to F1 generation. The F1 male rats from respective parents were separated for disease induction: group I animals (control) were administered with 500 µl of Milli-q water alone and group II (disease control), III (Microalga), and IV (fish oil) animals were administered with 2 g/kg bodyweight of MSG for 10 alternative days. Microalga-treated F1 rats showed significant HDL (43 mg/dl) levels when compared to their experimental groups. Brain tissues of microalga-treated F1 rats (MG) showed higher concentration of DHA (10.1 mg/100 mg tissue) and ARA (18.7 mg/100 mg tissue) levels and significant reduction of MDA (30 nM mg protein) levels. Furthermore, MSG induced neurotoxicity was ameliorated through the activation of CREB and BDNF genes The mRNA expressions of CREB and BDNF were 1.5-fold higher and NMDA levels were 2.0-fold higher in treated groups compared to disease control group. However, the expressions of antioxidant genes (SOD, catalase, and GPX) and apoptotic genes (Bcl-2 and Caspase-3) were significantly reduced in MG treated F1 rats when compared to disease control rats. Histopathological results also showed minimal focal damage in the tissues of MG F1 rats. Prenatal and continuous supply of microalgal biomass improves brain DHA and greatly reduced the consequences of MSG neurotoxicity in F1 rats.

Role of Lysocardiolipin Acyltransferase in Cigarette Smoke-Induced Lung Epithelial Cell Mitochondrial ROS, Mitochondrial Dynamics, and Apoptosis.

Cigarette smoke is the primary cause of Chronic Obstructive Pulmonary Disorder (COPD). Cigarette smoke extract (CSE)-induced oxidative damage of the lungs results in mitochondrial dysfunction and apoptosis of epithelium. Mitochondrial cardiolipin (CL) present in the inner mitochondrial membrane plays an important role in mitochondrial function, wherein its fatty acid composition is regulated by lysocardiolipin acyltransferase (LYCAT). In this study, we investigated the role of LYCAT expression and activity in mitochondrial oxidative stress, mitochondrial dynamics, and lung epithelial cell apoptosis. LYCAT expression was increased in human lung specimens from smokers, and cigarette smoke-exposed-mouse lung tissues. Cigarette smoke extract (CSE) increased LYCAT mRNA levels and protein expression, modulated cardiolipin fatty acid composition, and enhanced mitochondrial fission in the bronchial epithelial cell line, BEAS-2B in vitro. Inhibition of LYCAT activity with a peptide mimetic, attenuated CSE-mediated mitochondrial (mt) reactive oxygen species (ROS), mitochondrial fragmentation, and apoptosis, while MitoTEMPO attenuated CSE-induced MitoROS, mitochondrial fission and apoptosis of BEAS-2B cells. Collectively, these findings suggest that increased LYCAT expression promotes MitoROS, mitochondrial dynamics and apoptosis of lung epithelial cells. Given the key role of LYCAT in mitochondrial cardiolipin remodeling and function, strategies aimed at inhibiting LYCAT activity and ROS may offer an innovative approach to minimize lung inflammation caused by cigarette smoke.

ß-Cell specific transcription factors in the context of diabetes mellitus and ß-cell regeneration.

All pancreatic cell populations arise from the standard gut endoderm layer in developing embryos, requiring a regulatory gene network to originate and maintain endocrine lineages and endocrine function. The pancreatic organogenesis is regulated by the temporal expression of transcription factors and plays a diverse role in the specification, development, differentiation, maturation, and functional maintenance. Altered expression and activity of these transcription factors are often associated with diabetes mellitus. Recent advancements in the stem cells and invitro derived islets to treat diabetes mellitus has attracted a great deal of interest in the understanding of factors regulating the development, differentiation, and functions of islets including transcription factors. This review discusses the myriad of transcription factors regulating the development of the pancreas, differentiation of ß-islets, and how these factors regulated in normal and disease states. Exploring these factors in such critical context and exogenous or endogenous expression of development and differentiation-specific transcription factors with improved epigenetic plasticity/signaling axis in diabetic milieu would useful for the development of ß-cells from other cell sources.

Omega-3-rich Isochrysis sp. biomass enhances brain docosahexaenoic acid levels and improves serum lipid profile and antioxidant status in Wistar rats.

BACKGROUND: Isochrysis sp. is a marine microalga, rich in eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA). The potential use of its biomass as an alternative source of polyunsaturated fatty acids (PUFAs) has not been studied in animal models. Male albino Wistar rats were divided into three groups and treated for 28 days. The rats were fed with (1) standard chow (control group), (2) microalgal biomass rich in EPA and DHA along with standard chow (microalga group), and (3) fish oil that contains equivalent amounts of EPA and DHA along with standard chow (fish oil group). After intervention, biochemical indices, histopathological indices, relative mRNA expression of PUFA genes, antioxidant genes, inflammatory markers, and the fatty acid profile of major tissues were studied. RESULTS: Animals treated with microalgal biomass showed significantly increased serum HDL levels (P < 0.05) and reduced oxidative stress markers with a concomitant decrease in urea and creatinine levels. Oral supplementation of microalgal biomass did not show any toxicity or damage in any major organs. The mRNA expression of PUFA genes was significantly downregulated (P < 0.05) and antioxidant genes were upregulated. Furthermore, the mRNA expression of pro-inflammatory markers was significantly downregulated (P < 0.05) and anti-inflammatory markers were upregulated. Oral supplementation of microalgal biomass improved DHA status in brain and liver. CONCLUSION: The present study demonstrated that Isochrysis sp. can be used as a safe, alternative food supplement for ω-3 fatty acids. © 2019 Society of Chemical Industry.

Total antioxidant activity of selected vegetable oils and their influence on total antioxidant values in vivo: a photochemiluminescence based analysis.

This study evaluated the antioxidant activity of vegetable oils using photochemiluminescence based assay. The following oils were selected for the study - palm oil (PO); olive oil (OLO); sunflower oil (SNO); rice bran oil (RBO); sesame oil (SESO) and linseed oil (LSO). The antioxidant activity of oils was reduced significantly when unsaponifiable matter was removed from the oils. The rats fed unsaponifiable matter removed vegetable oils showed significantly reduced antioxidant activity but no change in overall fatty acid composition in serum lipids. Therefore the minor constituents in unsaponifiable matter influences antioxidant activity exhibited by vegetable oils.