Recyclable surgical, consumer, and industrial adhesives of poly(α-lipoic acid).

Polymer adhesives play an important role in many medical, consumer, and industrial products. Polymers of α-lipoic acid (αLA) have the potential to fulfill the need for versatile and environmentally friendly adhesives, but their performance is plagued by spontaneous depolymerization. We report a family of stabilized αLA polymer adhesives that can be tailored for a variety of medical or nonmedical uses and sustainably sourced and recycled in a closed-loop manner. Minor changes in monomer composition afforded a pressure-sensitive adhesive that functions well in dry and wet conditions, as well as a structural adhesive with strength equivalent to that of conventional epoxies. αLA surgical superglue successfully sealed murine amniotic sac ruptures, increasing fetal survival from 0 to 100%.

Taurine, alpha lipoic acid and vitamin B6 ameliorate the reduced developmental competence of immature mouse oocytes exposed to methylglyoxal.

Advanced glycation end products (AGEs) are the final products of the Maillard reaction, formed through the interaction of carbohydrates and proteins. Reactive dicarbonyl compounds such as methylglyoxal (MGO) serve as precursors for AGEs formation. Elevated levels of MGO/AGEs are observed in conditions like obesity, polycystic ovarian syndrome (PCOS), and diabetes, negatively impacting oocyte development. Previous studies have shown that hydrogen sulfide, a gasotransmitter with anti-AGEs effects, is produced in a process influenced by vitamin B6. R-α-lipoic acid (ALA) inhibits protein glycation and AGEs formation while stimulating glutathione (GSH) production. Taurine mitigates oxidative stress and acts as an anti-glycation compound, preventing in vitro glycation and AGEs accumulation. This study aimed to explore the ameliorative effects of a micronutrient support (Taurine, ALA and B6: TAB) on mouse oocytes challenged with MGO. Our results indicate that MGO reduces oocyte developmental competence, while TAB supplementation improves maturation, fertilization, and blastocyst formation rates. TAB also restores cell lineage allocation, redox balance and mitigates mitochondrial dysfunction in MGO-challenged oocytes. Furthermore, cumulus cells express key enzymes in the transsulfuration pathway, and TAB enhances their mRNA expression. However, TAB does not rescue MGO-induced damage in denuded oocytes, emphasizing the supportive role of cumulus cells. Overall, these findings suggest that TAB interventions may have significant implications for addressing reproductive dysfunctions associated with elevated MGO/AGEs levels. This study highlights the potential of TAB supplementation in preserving the developmental competence of COCs exposed to MGO stress, providing insights into mitigating the impact of dicarbonyl stress on oocyte quality and reproductive outcomes.

Hypoglycemia and Multivitamins.

Insulin autoimmune syndrome (IAS) is a rare condition triggered by exposure to various drugs containing sulfhydryl compounds, proton pump inhibitors, supplements, plasma proteins, viral infections like measles, influenza, hepatitis C, and autoimmune conditions like Graves' disease and systemic lupus erythematosus.1,3 We report two patients with recurrent episodes of hypoglycemia who were then diagnosed with IAS due to the consumption of α-lipoic acid (ALA) present in a multivitamin supplement. Eating small, frequent meals containing complex carbohydrates and steroids helps normalize blood glucose levels and reduce the insulin autoantibodies (IAA) to undetectable levels.3.

The Antioxidant and HDAC-Inhibitor α-Lipoic Acid Is Synergistic with Exemestane in Estrogen Receptor-Positive Breast Cancer Cells.

Anti-estrogenic therapy is established in the management of estrogen receptor (ER)-positive breast cancer. However, to overcome resistance and improve therapeutic outcome, novel strategies are needed such as targeting widely recognized aberrant epigenetics. The study aims to investigate the combination of the aromatase inhibitor exemestane and the histone deacetylase (HDAC) inhibitor and antioxidant α-lipoic acid in ER-positive breast cancer cells. First, the enantiomers and the racemic mixture of α-lipoic acid, and rac-dihydro-lipoic acid were investigated for HDAC inhibition. We found HDAC inhibitory activity in the 1-3-digit micromolar range with a preference for HDAC6. Rac-dihydro-lipoic acid is slightly more potent than rac-α-lipoic acid. The antiproliferative IC50 value of α-lipoic acid is in the 3-digit micromolar range. Notably, the combination of exemestane and α-lipoic acid resulted in synergistic behavior under various incubation times (24 h to 10 d) and readouts (MTT, live-cell fluorescence microscopy, caspase activation) analyzed by the Chou-Talalay method. α-lipoic acid increases mitochondrial fusion and the expression of apoptosis-related proteins p21, APAF-1, BIM, FOXO1, and decreases expression of anti-apoptotic proteins survivin, BCL-2, and c-myc. In conclusion, combining exemestane with α-lipoic acid is a promising novel treatment option for ER-positive breast cancer.

Outcomes of dietary alpha-lipoic acid on testicular vascularization, steroid hormones, and seminal quality in aged Baladi bucks.

BACKGROUND: Senescence is accompanied by a progressive decrease in male reproductive performance, mainly due to oxidative stress and endothelial dysfunction. Alpha lipoic acid (ALA) is a potent antioxidant, that diffuses freely in aqueous and lipid phases, possessing anti-inflammatory and anti-apoptotic properties. This study aimed to examine the effects of supplemental dietary ALA on testicular hemodynamics (TH), circulating hormones, and semen quality in aged goats. Twelve Baladi bucks were divided into two groups (n = 6 each); the first fed a basic ration and served as a control group (CON), while the second received the basic ration supplemented with 600 mg ALA/ kg daily for consecutive eight weeks (ALA). RESULTS: There were improvements in testicular blood flow in the ALA group evidenced by a lower resistance index (RI) and pulsatility index (PI) concurrent with higher pampiniform-colored areas/pixel (W3-W6). There were increases in testicular volume and decreases in echogenicity (W3-W5; ALA vs. CON). Compared to the CON, ALA-bucks had higher serum concentrations of testosterone, estradiol, and nitric oxide (W3-W5). There were enhancements in semen traits (progressive motility, viability, morphology, and concentration, alanine aminotransferase enzyme) and oxidative biomarkers (catalase, total antioxidant capacity, and malondialdehyde). CONCLUSIONS: ALA dietary supplementation (600 mg/kg diet) improved aged bucks' reproductive performance by enhancing the testicular volume, testicular hemodynamics, sex steroids, and semen quality.

Exogenous alpha-lipoic acid treatments reduce the oxidative damage caused by drought stress in two grapevine rootstocks.

Drought represents the predominant and most critical abiotic stress challenge within the domain of viticulture, necessitating the identification and application of efficacious strategies to ameliorate its deleterious effects. In the contemporary realm of abiotic stress management, the deployment of α-lipoic acid (α-Lipo), known for its antioxidant capabilities, as an exogenous treatment has been investigated for mitigating various abiotic stresses in numerous plant species, yet a detailed exploration of its efficacy in alleviating drought stress in grapevines remains to be conclusively determined. This study aimed to elucidate the adaptive mechanisms against drought stress by examining the effects of different α-Lipo concentrations (0, 1, 25 and 50 µM) applied on the foliar under well-irrigated and drought conditions on American grapevine rootstocks '1103 P' (drought tolerant) and '3309 C' (drought sensitive). Our findings revealed that the efficacy of α-Lipo varied significantly depending on rootstock type and irrigation status. 1103 P rootstock treated with 1 µM α-Lipo under well-irrigated conditions showed greater positive effects on growth traits, photosynthetic and osmotic parameters. In contrast, in rootstock 3309 C under the same conditions, the highest effects were obtained at 25 and 50 µM α-Lipo concentrations. Under drought stress conditions, 50 µM α-Lipo treatment improved physiological parameters (chlorophyll content, proportional water coverage and stomatal conductance), proline content and antioxidant enzyme activities (SOD, CAT and APX), while reducing electrolyte leakage and MDA levels in both rootstocks, showing a strong potential to increase oxidative stress tolerance and sustain plant growth. Heatmap visualization analysis confirmed the data obtained from Principal Component Analysis (PCA) and revealed that 1103 P treated with 50 µM α-Lipo under drought stress conditions exhibited superior physiological performance compared to 3309 C under the same conditions. This indicates the importance of potential rootstock differences in stress adaptation or α-Lipo uptake efficiency. These findings suggest that α-Lipo holds promise as an eco-friendly, natural bio-stimulant for use in arid environments, contributing to the advancement of sustainable agricultural practices in the foreseeable future.

Targeted nanoparticles triggered by plaque microenvironment for atherosclerosis treatment through cascade effects of reactive oxygen species scavenging and anti-inflammation.

Inflammatory factors and reactive oxygen species (ROS) are risk factors for atherosclerosis. Many existing therapies use ROS-sensitive delivery systems to alleviate atherosclerosis, which achieved certain efficacy, but cannot eliminate excessive ROS. Moreover, the potential biological safety concerns of carrier materials through chemical synthesis cannot be ignored. Herein, an amphiphilic low molecular weight heparin- lipoic acid conjugate (LMWH-LA) was used as a ROS-sensitive carrier material, which consisted of injectable drug molecules used clinically, avoiding unknown side effects. LMWH-LA and curcumin (Cur) self-assembled to form LLC nanoparticles (LLC NPs) with LMWH as shell and LA/Cur as core, in which LMWH could target P-selectin on plaque endothelial cells and competitively block the migration of monocytes to endothelial cells to inhibit the origin of ROS and inflammatory factors, and LA could be oxidized to trigger hydrophilic-hydrophobic transformation and accelerate the release of Cur. Cur released within plaques further exerted anti-inflammatory and antioxidant effects, thereby suppressing ROS and inflammatory factors. We used ultrasound imaging, pathology and serum analysis to evaluate the therapeutic effect of nanoparticles on atherosclerotic plaques in apoe-/- mice, and the results showed that LLC showed significant anti-atherosclerotic effects. Our finding provided a promising therapeutic nanomedicine for the treatment of atherosclerosis.

Effect of compound treatments on mouse lens viscoelasticity.

Previous studies have shown that pharmaceutical agents such as lipoic acid have the ability to soften the lens, presenting a promising avenue for treating presbyopia. One obstacle encountered in the preclinical stage of such agents is the need for precise measurements of lens elasticity in experimental models. This study aimed to evaluate the effects of 25-hydroxycholesterol, lipoic acid, and obeticholic acid on the viscoelastic properties of mouse lenses using a custom-built elastometer system. Data were acquired on lenses from C57BL/6J female mice from two age groups: young (age: 8-10 weeks) and old (age: 32-43 weeks). OD lenses were used as the control and OS lenses were treated. Control lenses were immersed in Dulbecco's Modified Eagle Medium (DMEM) and treatment lenses were immersed in a compound solution containing 25-hydroxycholesterol (5 young and 5 old), lipoic acid at 2.35 mM (5 young and 5 old), lipoic acid at 0.66 mM (5 old), or obeticholic acid (5 old) at 37 °C for 18 h. After treatment, the mouse lenses were placed in a DMEM-filled chamber within a custom-built elastometer system that recorded the load and lens shape as the lens was compressed by 600 µm at a speed of 50 µm/s. The load was continuously recorded during compression and during stress-relaxation. The compression phase was fit with a linear function to quantify lens stiffness. The stress-relaxation phase was fit with a 3-term exponential relaxation model providing relaxation time constants (t1, t2, t3), and equilibrium load. The lens stiffness, time constants and equilibrium load were compared for the control and treated groups. Results revealed an increase in stiffness with age for the control group (young: 1.16 ± 0.11 g/mm, old: 1.29 ± 0.14 g/mm) and relaxation time constants decreased with age (young: t1 = 221.9 ± 29.0 s, t2 = 24.7 ± 3.8 s, t3 = 3.12 ± 0.87 s, old: t1 = 183.0 ± 22.0 s, t2 = 20.6 ± 2.6 s and t3 = 2.24 ± 0.43 s). Among the compounds tested, only 25-hydroxycholesterol produced statistically significant changes in the lens stiffness, relaxation time constants, and equilibrium load. In conclusion, older mouse lenses are stiffer and less viscous than young mouse lenses. Notably, no significant change in lens stiffness was observed following treatment with lipoic acid, contrary to previous findings.

Hepatoprotective potential of alpha-lipoic acid against gliclazide-induced liver injury in high-glucose-exposed human liver cells and experimental type 2 diabetic rats.

Growing clinical evidence shows that sulfonylurea therapy for patients with type 2 diabetic mellitus (T2DM) contributes to progressive worsening of their liver. The present study presents hepatotoxicity induced by gliclazide, a second-generation sulfonylurea, and alpha-lipoic acid (ALA) as a novel and promising drug for T2DM treatment. Normal human liver cells (HL-7702) were incubated with high-glucose DMEM in the presence or absence of gliclazide and ALA for 72 h, and cell viability and death were measured by flow cytometry. Next, Sprague-Dawley rats were subjected to 12 h of fasting, and fasting blood glucose was measured. The rats were randomized into four groups: HC (healthy control; n = 7), T2DM (diabetic rats without treatment; n = 9), GLC (diabetic rats with 15 mg/kg gliclazide treatment; n = 7) and GLC+ALA (diabetic rats with gliclazide and 60 mg/kg ALA treatment; n = 7). T2DM was induced by a bolus administration of 110 mg/kg nicotinamide and 55 mg/kg streptozotocin intraperitoneally. The experimental protocol lasted for 6 weeks after which the animals were sacrificed and pancreas, liver and blood samples were collected for biochemical, histological and molecular analyses. Compared to healthy control (HC) group, exposure of HL-7702 cells to high glucose induced significant cell death by 19 % (p < 0.001), which was exacerbated with gliclazide treatment by 29 % (p < 0.0001) but markedly reduced by 6 % to near HC value following ALA treatment. In vivo, GLC-treated rats had severe liver damage characterized by increased hepatocellular vacuolation, and significant expression of ED-1, iNOS and caspase-3 as well as markedly high levels of liver enzymes (aspartate aminotransferase, alanine aminotransferase and alkaline phosphatase compared to T2DM rats. Interestingly, ALA administration prevented these pathological changes and protected the diabetic liver to levels comparable to HC rats. ALA showed hepatoprotective effect against gliclazide-induced hepatotoxicity by suppressing inflammation and apoptosis while activating antioxidant pathway in the diabetic liver. Abbreviations: ALA, Alpha-lipoic acid; ALT, Alanine aminotransferase; ALP, Alkaline phosphatase; AMPK, Adenosine monophosphate-activated protein kinase; AST, Aspartate aminotransferase; ATP, Adenosine triphosphate; DMEM, Dulbecco's Modified Eagle Medium; EDTA, ethylenediaminetetraacetic acid; FBG, Fasting blood glucose; FBS, Fetal bovine serum; GLC, Gliclazide; GLUT4, Glucose transporter type 4; GSH, Glutathione; H&E, Hematoxylin/Eosin; HbA1c, Glycosylated haemoglobin A1c; HC, Healthy control; HG, Hyperglycemic group; HOMA-ß, Homeostasis model assessment of ß-cell function; IL-1ß, Interleukin-1ß; IL-6, Interleukin-6; iNOS, Inducible nitric oxide synthase; KATP, ATP-dependent potassium channels; MDA, Malondialdehyde; MPTP, Mitochondrial permeability transition pore; NO, Nitric oxide; P/S, Penicillin/streptomycin; PAS, Periodic acid-Schiff; RIA, Radioimmunoassay; ROS, Reactive oxygen species; SOD, Superoxide dismutase; T2DM, Type 2 diabetes mellitus; TBARS, Thiobarbituric acid reactive substances; TNF-α, Tumor necrosis factor-alpha.

Protective effects of the R-(+)-thioctic acid treatment: possible anti-inflammatory activity on heart of hypertensive rats.

BACKGROUND: In cardiovascular disease, high blood pressure is associated with oxidative stress, promoting endothelial dysfunction, vascular remodeling, and inflammation. Clinical trials are discordant that the most effective treatment in the management of hypertension seems to be the administration of anti-hypertensive drugs with antioxidant properties. The study aims to evaluate the effects of the eutomer of thioctic acid on oxidative stress and inflammation in the heart of spontaneously hypertensive rats compared to normotensive Wistar Kyoto rats. METHODS: To study the oxidative status, the malondialdehyde and 4-hydroxynonenal concentration, protein oxidation were measured in the heart. Morphological analysis were performed. Immunohistochemistry and Western blot were done for alpha-smooth muscle actin and transforming growth factor beta to assess fibrosis; cytokines and nuclear factor kappaB to assess inflammatory processes. RESULTS: Spontaneously hypertensive rats were characterized by hypertension with increased malondialdehyde levels in the heart. OxyBlot in the heart of spontaneously hypertensive rats showed an increase in proteins' oxidative status. Cardiomyocyte hypertrophy and fibrosis in the ventricles were associated with an increased expression of alpha-smooth muscle actin and pro-inflammatory cytokines, reduced by the eutomer of thioctic acid supplementation. CONCLUSIONS: Based on this evidence, eutomer of thioctic acid could represent an appropriate antioxidant molecule to reduce oxidative stress and prevent inflammatory processes on the cardiomyocytes and cardiac vascular endothelium.

Potential effects of Resatorvid and alpha lipoic acid on gentamicin-induced nephrotoxicity in rats.

Gentamicin is an aminoglycoside antibiotic with a rapid bactericidal effect on the treatment of many infections. However, its use at high concentrations for more than 7 days causes nephrotoxic side effects. This study investigated the potential of Resatorvid and alpha lipoic acid (ALA) in mitigating gentamicin-induced nephrotoxicity in rats, considering biochemical, histopathological, and molecular parameters. This study randomly distributed 34 Wistar albino rats into four groups: healthy control (n = 6), Gentamicin (80 mg/kg, n = 7), Gentamicin + Sham (%10 hydroalcoholic solution, n = 7), Gentamicin + Resatorvid (5 mg/kg, n = 7), and Gentamicin + ALA (100 mg/kg, n = 7). Resatorvid treatment led to a statistically significant decrease in urinary IL-18, KIM-1, and NGAL levels, whereas ALA treatment significantly reduced KIM-1 levels compared to the gentamicin-only group. Both Resatorvid and ALA showed partial reductions in urine creatinine levels. Moreover, treatments with Resatorvid and ALA resulted in statistically significant decreases in NRF-2, CAS-3, and NR4A2 expressions. However, only Resatorvid demonstrated a statistically significant decrease in NF-B expression. These findings highlight the potential of Resatorvid in ameliorating gentamicin-induced nephrotoxicity, thereby expanding the therapeutic utility of gentamicin and enhancing its efficacy against infections.

Alpha-lipoic acid alleviates cognitive deficits in transgenic APP23/PS45 mice through a mitophagy-mediated increase in ADAM10 α-secretase cleavage of APP.

BACKGROUND: Alpha-lipoic acid (ALA) has a neuroprotective effect on neurodegenerative diseases. In the clinic, ALA can improve cognitive impairments in patients with Alzheimer's disease (AD) and other dementias. Animal studies have confirmed the anti-amyloidosis effect of ALA, but its underlying mechanism remains unclear. In particular, the role of ALA in amyloid-ß precursor protein (APP) metabolism has not been fully elucidated. OBJECTIVE: To investigate whether ALA can reduce the amyloidogenic effect of APP in a transgenic mouse model of AD, and to study the mechanism underlying this effect. METHODS: ALA was infused into 2-month-old APP23/PS45 transgenic mice for 4 consecutive months and their cognitive function and AD-like pathology were then evaluated. An ALA drug concentration gradient was applied to 20E2 cells in vitro to evaluate its effect on the expression of APP proteolytic enzymes and metabolites. The mechanism by which ALA affects APP processing was studied using GI254023X, an inhibitor of A Disintegrin and Metalloproteinase 10 (ADAM10), as well as the mitochondrial toxic drug carbonyl cyanide m-chlorophenylhydrazone (CCCP). RESULTS: Administration of ALA ameliorated amyloid plaque neuropathology in the brain tissue of APP23/PS45 mice and reduced learning and memory impairment. ALA also increased the expression of ADAM10 in 20E2 cells and the non-amyloidogenic processing of APP to produce the 83 amino acid C-terminal fragment (C83). In addition to activating autophagy, ALA also significantly promoted mitophagy. BNIP3L-knockdown reduced the mat/pro ratio of ADAM10. By using CCCP, ALA was found to regulate BNIP3L-mediated mitophagy, thereby promoting the α-cleavage of APP. CONCLUSIONS: The enhanced α-secretase cleavage of APP by ADAM10 is the primary mechanism through which ALA ameliorates the cognitive deficits in APP23/PS45 transgenic mice. BNIP3L-mediated mitophagy contributes to the anti-amyloid properties of ALA by facilitating the maturation of ADAM10. This study provides novel experimental evidence for the treatment of AD with ALA.

(+)Alpha-Lipoic Acid Regulates Lipid Metabolism Gene Expression and Lipidic Profile in a Cellular Model of Fatty Acid Overload.

BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved treatments are currently lacking. This study explores the potential therapeutic impact of alpha-lipoic acid (ALA), a natural compound crucial in lipid metabolism, on NAFLD using an in vitro model. METHODS: HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles. RESULTS: Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways. CONCLUSION: In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD.

Efficacy of melanin-loaded lipoic acid-modified chitosan hydrogel in diabetic wound healing.

The healing of diabetic wounds is significantly impeded due to severe oxidative stress and hindered angiogenesis, presenting a major challenge to clinical treatment. In this context, we introduces a novel hydrogel dressing strategy that uniquely combines α-lipoic acid-modified chitosan (LAMC) and melanin nanoparticles (MNPs). This innovative hydrogel, LAMC@MNPs, is formulated to gel under ultraviolet (UV) light without the need for a photoinitiator, simplifying the preparation process and potentially enhancing safety. Our experimental results demonstrate that the LAMC@MNPs hydrogel not only exhibits superior skin adhesion, with an average strength of 56.59 ± 3.16 KPa, but also effectively alleviates oxidative stress and accelerates vascular regeneration and wound healing. This is achieved by promoting cell migration and scavenging free radicals, addressing the critical barriers in diabetic wound care. The combination of these materials and their functional benefits presents a promising new approach to diabetic wound treatment.

Exploration of dietary interventions to treat mitochondrial fatty acid disorders in a mouse model.

Mitochondrial fatty acids synthesis (mtFAS) is a conserved metabolic pathway essential for mitochondrial respiration. The best characterized mtFAS product is the medium-chain fatty acid octanoate (C8) used as a substrate in the synthesis of lipoic acid (LA), a cofactor required by several mitochondrial enzyme complexes. In humans, mutations in the mtFAS component enoyl reductase MECR cause childhood-onset neurodegenerative disorder MEPAN. A complete deletion of Mecr in mice is embryonically lethal, while selective deletion of Mecr in cerebellar Purkinje cells causes neurodegeneration in these cells. A fundamental question in the research of mtFAS deficiency is if the defect is amenable to treatment by supplementation with known mtFAS products. Here we used the Purkinje-cell specific mtFAS deficiency neurodegeneration model mice to study if feeding the mice with a medium-chain triacylglycerol-rich formula supplemented with LA could slow down or prevent the neurodegeneration in Purkinje cell-specific Mecr KO mice. Feeding started at the age of 4 weeks and continued until the age of 9 months. The neurological status on the mice was assessed at the age of 3, 6, and 9 months with behavioral tests and the state of the Purkinje cell deterioration in the cerebellum was studied histologically. We showed that feeding the mice with medium chain triacylglycerols and LA affected fatty acid profiles in the cerebellum and plasma but did not prevent the development of neurodegeneration in these mice. Our results indicate that dietary supplementation with medium chain fatty acids and LA alone is not an efficient way to treat mtFAS disorders.

Pathological biopsy strategy by regulating intracellular ROS to precisely differentiate cancer cells from diseased tissues.

We have developed an innovative pathological biopsy strategy by expanding the differences of ROS levels among cancer cells, inflammatory cells and normal cells using cross-linked lipoic acid vesicles loaded with vitamin C (VC@cLAVs), combined with chemiluminescence imaging technology. By analyzing the different trends of intracellular chemiluminescence intensity, the three types of cells were quickly and accurately differentiated from diseased tissues, thus holding clinical tumor diagnostic potential.

Alpha lipoic acid mitigates adverse impacts of drought stress on growth and yield of mungbean: photosynthetic pigments, and antioxidative defense mechanism.

Context: Exogenous use of potential organic compounds through different modes is a promising strategy for the induction of water stress tolerance in crop plants for better yield. Aims: The present study aimed to explore the potential role of alpha-lipoic acid (ALA) in inducing water stress tolerance in mungbean lines when applied exogenously through various modes. Methods: The experiment was conducted in a field with a split-plot arrangement, having three replicates for each treatment. Two irrigation regimes, including normal and reduced irrigation, were applied. The plants allocated to reduced irrigation were watered only at the reproductive stage. Three levels of ALA (0, 0.1, 0.15 mM) were applied through different modes (seed priming, foliar or priming+foliar). Key results: ALA treatment through different modes manifested higher growth under reduced irrigation (water stress) and normal irrigation. Compared to the other two modes, the application of ALA as seed priming was found more effective in ameliorating the adverse impacts of water stress on growth and yield associated with their better content of leaf photosynthetic pigments, maintenance of plant water relations, levels of non-enzymatic antioxidants, improved activities of enzymatic antioxidants, and decreased lipid peroxidation and H2O2 levels. The maximum increase in shoot fresh weight (29% and 28%), shoot dry weight (27% and 24%), 100-grain weight (24% and 23%) and total grain yield (20% and 21%) in water-stressed mungbean plants of line 16003 and 16004, respectively, was recorded due to ALA seed priming than other modes of applications. Conclusions: Conclusively, 0.1 and 0.15 mM levels of ALA as seed priming were found to reduce the adverse impact of water stress on mungbean yield that was associated with improved physio-biochemical mechanisms. Implications: The findings of the study will be helpful for the agriculturalists working in arid and semi-arid regions to obtain a better yield of mungbean that will be helpful to fulfill the food demand in those areas to some extent.

A D-π-A-type ratiometric fluorescent probe to detect polarity changes and inhibition effect during ferroptosis.

To thoroughly understand ferroptosis's biological functions in living cells, it is crucial to investigate the polarity variations that occur during this unique Fe(II)-facilitated oxidative type of cell death. In this work, we report the development of a ratiometric probe (Po-P) to visualize the polarity changes in living cells and the inhibition effect during ferroptosis. The polarity-responsive fluorophore utilized by Po-P has a D-π-A-type structure. Based on theoretical calculations, ICT was proposed as the basis for Po-P's polarity-responsive mechanism. According to cell imaging results, Po-P had a desirable capacity for monitoring polarity fluctuations and erastin-induced ferroptosis. Furthermore, inhibition imaging revealed that dihydrolipoic acid (DHLA) could potentially prevent polarity changes that occur during erastin-induced ferroptosis, just as vitamin E (VE). We anticipate that the probe Po-P could be a valuable tool to quickly monitor polarity fluctuations and inhibition effects during ferroptosis and create new medications for treating disorders related to ferroptosis.

Ceria Nanoparticle Systems Alleviate Degenerative Changes in Mouse Postovulatory Aging Oocytes by Reducing Oxidative Stress and Improving Mitochondrial Functions.

Postovulatory aging oocytes usually feature diminished potential for fertilization and poor embryonic development due to enhanced oxidative damage to the subcellular organelles and macromolecules, which stands as a formidable obstacle in assisted reproductive technologies (ART). Here, we developed lipoic acid (LA) and polyethylene glycol (PEG)-modified CeO2 nanoparticles (LA-PEG-CeNPs) with biocompatibility, enzyme-like autocatalytic activity, and free radical scavenging capacity. We further investigated the LA-PEG-CeNPs effect in mouse postovulatory oocytes during in vitro aging. The results showed that LA-PEG-CeNPs dramatically reduced the accumulation of ROS in aging oocytes, improving mitochondrial dysfunction; they also down-regulated the pro-apoptotic activity by rectifying cellular caspase-3, cleaved caspase-3, and Bcl-2 levels. Consistently, this nanoenzyme prominently alleviated the proportion of abnormalities in spindle structure, chromosome alignment, microtubule stability, and filamentous actin (F-actin) distribution in aging oocytes, furthermore decreased oocyte fragmentation, and improved its ability of fertilization and development to blastocyst. Taken together, our finding suggests that LA-PEG-CeNPs can alleviate oxidative stress damage on oocyte quality during postovulatory aging, implying their potential value for clinical practice in assisted reproduction.

Substrate Analogues Entering the Lipoic Acid Salvage Pathway via Lipoate-Protein Ligase 2 Interfere with Staphylococcus aureus Virulence.

Lipoic acid (LA) is an essential cofactor in prokaryotic and eukaryotic organisms, required for the function of several multienzyme complexes such as oxoacid dehydrogenases. Prokaryotes either synthesize LA or salvage it from the environment. The salvage pathway in Staphylococcus aureus includes two lipoate-protein ligases, LplA1 and LplA2, as well as the amidotransferase LipL. In this study, we intended to hijack the salvage pathway by LA analogues that are transferred via LplA2 and LipL to the E2 subunits of various dehydrogenases, thereby resulting in nonfunctional enzymes that eventually impair viability of the bacterium. Initially, a virtual screening campaign was carried out to identify potential LA analogues that bind to LplA2. Three selected compounds affected S. aureus USA300 growth in minimal medium at concentrations ranging from 2.5 to 10 µg/mL. Further analysis of the most potent compound (Lpl-004) revealed its transfer to E2 subunits of dehydrogenase complexes and a negative impact on its functionality. Growth impairment caused by Lpl-004 treatment was restored by adding products of the lipoate-dependent enzyme complexes. In addition, Caenorhabditis elegans infected with LpL-004-treated USA300 demonstrated a significantly expanded lifespan compared to worms infected with untreated bacteria. Our results provide evidence that LA analogues exploiting the LA salvage pathway represent an innovative strategy for the development of novel antimicrobial substances.