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Elastomers with high strength and toughness, excellent self-healing properties, and biocompatibility have broad application prospects in wearable electronics and other fields, but preparing it remains a challenge. In this work, we propose a highly adaptable strategy by introducing the small molecule crosslinking agent of triethanolamine (TEA) to the poly thioctic acid (PTA) chains and preparing the PAxEy elastomers using a simple synthesis step. This strategy stabilizes the PTA chains by constructing multiple non-covalent cross-linked dynamic networks, endowing materials with excellent strength and toughness (tensile strength of 288 kPa, toughness of 278.2 kJ/m3), admirable self-healing properties (self-healing efficiency of 121.6% within 7 h at 70 °C), and good biocompatibility. The PAxEy elastomers can also be combined with MWNTs to become flexible strain sensors, which can be used to monitor human joint movements with high sensitivity, repeatable responses, and stability. [ABSTRACT FROM AUTHOR]

Hepatocellular carcinoma (HCC) associated with viral or metabolic liver diseases is a growing cancer without effective therapy. AMPK is downregulated in HCC and its activation diminishes tumor growth. Alpha lipoic acid (ALA), an indirect AMPK activator that inhibits hepatic steatosis, shows antitumor effects in different cancers. We aimed to study its putative action in liver-cancer derived cell lines through AMPK signaling. We performed cytometric studies for apoptosis and cell cycle, and 2D and 3D migration analysis in HepG2/C3A and Hep3B cells. ALA led to significant inhibition of cell migration/invasion only in HepG2/C3A cells. We showed that these effects depended on AMPK, and ALA also increased the levels and nuclear compartmentalization of the AMPK target p53. The anti-invasive effect of ALA was abrogated in stable-silenced (shTP53) versus isogenic-TP53 HepG2/C3A cells. Furthermore, ALA inhibited epithelial-mesenchymal transition (EMT) in control HepG2/C3A but not in shTP53 nor in Hep3B cells. Besides, we spotted that in patients from the HCC-TCGA dataset some EMT genes showed different expression patterns or survival depending on TP53. ALA emerges as a potent activator of AMPK-p53 axis in HCC cells, and it decreases migration/invasion by reducing EMT which could mitigate the disease in wild-type TP53 patients. [ABSTRACT FROM AUTHOR]

Cytarabine, an anti-metabolite drug, remains the mainstay of treatment for hematological malignancies. It causes various toxic effects including teratogenicity. Alpha lipoic acid (ALA) is a natural antioxidant reported to offer protection against hepatotoxicity induced by various pathological conditions, drugs, or chemicals. We investigated the protective effect of ALA against prenatal cytarabine exposure-induced hepatotoxicity in rat female neonates. A total of 30 dams were randomly assigned to five groups and received normal saline, ALA 200 mg/kg, cytarabine 12.5 mg/kg, cytarabine 25 mg/kg, and cytarabine 25 mg/kg + ALA 200 mg/kg, respectively, from gestational day (GD)8 to GD21. Cytarabine and ALA were administered via intraperitoneal and oral (gavage) routes, respectively. On postnatal day (PND)1, all the live female neonates (pups) were collected and weighed. The blood and liver from pups were carefully collected and used for histopathological, and biochemical evaluations. A significant and dose-dependent decrease in maternal food intake and weight gain was observed in the pregnant rats (dams) of the cytarabine groups as compared to the dams of the control group. The pups exposed to cytarabine showed a significant and dose-dependent (a) decrease in body weight, liver weight, hepatosomatic index, catalase, superoxide dismutase, glutathione, glutathione peroxidase, serum albumin levels and (b) increase in malondialdehyde, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase, AST/ALT ratio, and histopathological anomalies. Maternal co-administration of ALA ameliorated these biochemical changes and histopathological abnormalities by combating oxidative stress. Future studies are warranted to explore the molecular mechanisms involved in the ALA's protective effects against prenatal cytarabine-induced hepatotoxicity. [ABSTRACT FROM AUTHOR]

In this study, the influence of modified nanosilica on the curing, mechanical, and swelling resistance properties of natural rubber and ethylene-propylene-diene monomer blends (NR/EPDM; 70/30 phr/phr) was examined. The composites were developed using the melt compounding method, with nanosilica derived from rice husk ash serving as the reinforcing nanofiller in NR/EPDM composites. Two modifiers were employed in this study: a 2:1 ratio of TESPT (bis(3-triethoxysilylpropyl)tetrasulfide) to TWEEN-20 (polyoxyethylene (20) sorbitan monolaurate) (Modifier 1), and thioctic acid (TA) (Modifier 2). In comparison to pure NR/EPDM blends, the inclusion of TA-modified nanosilica significantly enhanced tensile and tear strength by up to 76% and 48%, respectively. Moreover, NR/EPDM nanocomposites filled with TA-modified nanosilica exhibited reduced swelling at a given loading when compared to their counterparts filled with TESPT/TWEEN-20-modified nanosilica. [ABSTRACT FROM AUTHOR]

Water temperature is a major environmental factor affecting fish activity, physiology, behavior, and growth. Alpha lipoic acid (ALA) has garnered much attention lately as an aqua feed supplement because of its antioxidant effects. Thus, this study aimed to assess the effect of dietary ALA on performance, hematological and immunological indices, behavior and oxidative stress, apoptosis, and genetic inflammation in Oreochromis niloticus following 60 days of cold stress. Two hundred forty fish were divided into four groups (15 fish/replicate, N = 60 fish/group). The control (CNT) and ALA groups were reared at 25 °C and fed a basal diet without any supplementation or a basal diet containing 600 mg ALA/kg diet, respectively. The cold water-stressed group (CWS) and ALA + CWS groups were reared at 18 °C and fed basal and basal diets containing ALA, respectively. The results revealed that dietary ALA supplementation significantly improved feed utilization and growth in fish. ALA also mitigated CWS-induced microcytic hypochromic anemia and hyperlipidemia. Moreover, ALA supplementation considerably enhanced the antioxidant status and boosted intestinal α amylase, lipase, protease, and serum acetylcholinesterase activity of CWS-exposed fish. Besides, ALA supplementation significantly reversed CWS-induced upregulation of proinflammatory genes, pro-apoptotic genes, heat shock protein, and proliferating cell nuclear antigen or downregulation of superoxide dismutase and catalase gene expressions in liver and spleen tissues. Furthermore, ALA supplementation reduced CWS-induced histopathological alterations in fish liver, spleen, and intestine. We can conclude that ALA (600 mg/kg diet) could be recommended as an aqua feed supplement to boost growth, antioxidant capacity, and immunity and attenuate inflammatory and apoptotic reactions of fish reared under CWS-induced. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hypothyroidism has adverse effects on heart metabolism and functions including reduced heart rate, cardiac output and cardiac contractility. The therapeutic effects of alpha lipoic acid (LA) and metformin (MET) against hypothyroidism-induced myocardial complications were assessed in the current study. Rats were divided into control, propylthiouracil (PTU)-induced hypothyroidism model, hypothyroidism model treated with LA and/or MET. Serum thyroid hormones (T3, T4 and TSH) were measured. Lipid peroxidation (MDA), nitric oxide (NO), reduced glutathione (GSH), nuclear factor erythroid 2–related factor 2 (NrF2), B-cell lymphoma 2 (BCL2), nuclear factor kappa B (NF-κB), serotonin (5-HT), norepinephrine (NE) and dopamine (DA), acetylcholinesterase (AChE), monoamine oxidase (MAO) and Na+,K+,ATPase were measured in the cardiac tissue. The histopathological changes were also assessed. PTU significantly decreased T3 and T4 and significantly increased TSH. A significant increase in MDA, GSH, NrF2, BCL2, NF-κB, 5-HT, NE, DA, AChE, MAO and Na+,K+,ATPase and a significant decrease in NO were observed in the cardiac tissue of hypothyroidism model. This was associated with histopathological changes. LA alone or with MET restored T3 and TSH and improved almost all the biochemical changes except the decreased NO and the increased DA. MET restored T3, T4 and TSH and the biochemical changes induced in the cardiac tissue. MET ameliorated the histopathological changes that were still observed with LA alone or with MET. The present findings indicate that MET had cardioprotective effect against hypothyroidism and its myocardial complications. This effect was less prominent with LA alone or in combination with MET. [ABSTRACT FROM AUTHOR]

The effect of thioctic acid (TA), 2-ethyl-6-methyl-3-hydroxypyridine hydrochloride (emoxypine), and their ester derivative (2-ethyl-6-methylpyridinol-3-yl-thiooctanoate, thioxypine) on the behavior of rats in an elevated plus maze (EPM) was studied. Intraperitoneal administration (three times) of TA, emoxypine, and their equimolar mixture in single doses of 36.25, 72.5, and 145 μmol/kg enhanced individual manifestations of anxious behavior in the EPM but did not cause full-blown anxiogenic effects. Similar pro-anxiogenic effects were observed when TA was administered in a dose of 36.25 μmol/kg and emoxypine in doses of 72.5 and 145 μmol/kg. The equimolar mixture of the non-esterified components of thioxypine had a pro-anxiogenic effect in doses of 36.25 and 72.5 μmol/kg. Combination of TA and 2-ethyl-6-methyl-3-hydroxypyridine into the ester potentiated their pro-anxiogenic activity, which manifested as an extensive anxiogenic effect of thioxypine when administered three times in a dose of 145 μmol/kg. [ABSTRACT FROM AUTHOR]

Purpose: Although COVID-19 anosmia is often transient, patients with persistent olfactory dysfunction (pOD) can experience refractory parosmia and diminished smell. This study evaluated four putative therapies for parosmia in patients with chronic COVID-19 olfactory impairment. Methods: After screening nasal endoscopy, 85 patients (49 female, 58%) with pOD and treatment-refractory parosmia were randomized to: (1) ultramicronized palmitoylethanolamide and luteolin + olfactory training (OT) (umPEALUT group, n = 17), (2) alpha-lipoic acid + OT (ALA group, n = 21), (3) umPEALUT + ALA + OT (combination group, n = 28), or 4) olfactory training (OT) alone (control group, n = 23). Olfactory function was assessed at baseline (T0) and 6 months (T1) using a parosmia questionnaire and Sniffin' Sticks test of odor threshold, detection, and identification (TDI). Analyses included one-way ANOVA for numeric data and Chi-Square analyses for nominal data on parosmia. Results: The umPEALUT group had the largest improvement in TDI scores (21.8 ± 9.4 to 29.7 ± 7.5) followed by the combination group (19.6 ± 6.29 to 27.5 ± 2.7), both p < 0.01. The control and ALA groups had no significant change. Patients in the combination and umPEALUT groups had significantly improved TDI scores compared to ALA and control groups (p < 0.001). Rates of parosmia resolution after 6 months were reported at 96% for combination, 65% for control, 53% for umPEALUT and 29% for ALA (p < 0.001). All treatment regimens were well-tolerated. Conclusions: umPEALUT and OT, with or without ALA, was associated with improvement in TDI scores and parosmia, whereas OT alone or OT with ALA were associated with little benefit. [ABSTRACT FROM AUTHOR]

Lipoic acid (LA), a unique antioxidant compound, can stimulate the antioxidant defense system in plants subjected to abiotic stresses. We aimed to determine the role of LA in induction of the antioxidant system at lower reactive oxygen species (ROS), ascorbate (ASC) and glutathione (GSH) levels in osmotic-stressed maize (Zea mays L.). For this purpose, ROS, GSH and ASC contents were decreased using N,N'‑dimethylthiourea (DMTU), L-buthionine sulfoximine (BSO) and acriflavine (AF), respectively. Pots containing 21-day-old seedlings were divided into nine groups consisting of a non-stressed group; polyethylene glycol6000 (PEG)-induced osmotic stress (PEG) group, LA, DMTU, BSO and AF treatment groups; and DMTU, BSO, and AF-combined LA treatment groups under osmotic stress. ROS contents and membrane damage after the DMTU, BSO, and AF-combined LA treatments were lower than those after the DMTU, BSO, and AF treatments, respectively. Moreover, the LA treatments in combination with DMTU, BSO and AF increased dry weight, activities of antioxidant enzymes (superoxide dismutase, catalase, ascorbate peroxidase, glutathione reductase, monodehydroascorbate reductase and dehydroascorbate reductase), and contents of GSH, ASC, and LA compared to the DMTU, BSO and AF treatments. Additionally, the relative expression levels of SUPEROXIDE DISMUTASE, CATALASE1 and ASCORBATE PEROXIDASE1 genes were consistent with the findings for their related antioxidant enzyme activities. These results indicated that LA could adjust ROS level and maintain stimulation of the antioxidant system at lower ROS, GSH, and ASC levels in osmotic stressed maize. Furthermore, LA may play a signaling role and assume the function of ASC and GSH in maize under PEG-induced osmotic stress. [ABSTRACT FROM AUTHOR]

Background: Obstructive sleep apnea–hypopnea syndrome (OSAHS) is a common respiratory disease with potential lethality. At present, the commonly used treatment method is continuous positive airway pressure ventilation, but with the prolongation of the course of the disease, the effect of single ventilation on the improvement of oxidative stress levels is not good. Lipoic acid is a commonly used antioxidant in clinics. In this paper, lipoic acid combined with continuous positive airway pressure ventilation is used to explore whether it has a better therapeutic effect on patients. Aim: To probe into the clinical efficacy of lipoic acid combined with continuous positive airway pressure ventilation in the therapy of OSAHS. Methods: 82 patients with OSAHS who were cured in our hospital from March 2021 to September 2022 were prospectively collected as subjects. Based on different treatment methods, patients were grouped into a control group (43 cases) and an observation group (39 cases). The control group was treated with continuous positive airway pressure (CPAP), and the observation group was treated with lipoic acid based on control group. The therapeutic effects were measured by apnea hypopnea index (AHI), oxygen saturation (SpO2), mean oxygen saturation (MSpO2), serum malondialdehyde (MDA), superoxide dismutase (SOD), hypoxia inducible factor-1α (HIF-1α) levels, peripheral blood γ-aminobutyric acid, melatonin levels. Results: The clinical effectiveness of the observation group was better (P < 0.05). After treatment, AHI, the levels of MDA and HIF-1α in the observation group were lower and SpO2, MSpO2 and the level of SOD, γ- aminobutyric acid, and melatonin were higher than those in the control group (P < 0.05). The levels of γ- aminobutyric acid and melatonin were negatively correlated with the severity of symptoms, ESS, and AIS scores (P < 0.05). Conclusions: The clinical effect of lipoic acid combined with CPAP in the treatment of OSAHS is better, and it has a positive effect on the levels of γ-aminobutyric acid and melatonin in peripheral blood. Lipoic acid was added to the original method for treatment, and the therapeutic effect was greatly improved. [ABSTRACT FROM AUTHOR]

Aims: Cytarabine (CYT), a prevalent anticancer drug for blood cancers, detrimentally affects male reproductive development and function. Alpha-lipoic acid (ALA), a universal antioxidant, offers defense against chemical-induced reproductive dysfunction. Our study sought to explore ALA's protective role against prenatal CYT-induced reproductive impairment in F1 male adult rats. Main methods: Pregnant rats were divided into 5 groups and administered normal saline, ALA 200 mg/kg, CYT 12.5 mg/kg, CYT 25 mg/kg, and CYT 25 mg/kg + ALA 200 mg/ kg from gestational day 8 to 21. On postnatal day 73, F1 male rats were sacrificed, and general, oxidative, steroidogenic, spermatogenic, histological, and morphometrical parameters were evaluated. Key findings: Prenatal CYT caused dose-dependent reductions in body weight, testis, and accessory gland weights; elevated oxidative stress; delayed puberty onset; sperm anomalies (decreased count, motility, viability, seminal fructose; increased morphological anomalies); impeded steroidogenesis (lower testosterone, follicle-stimulating hormone, luteinizing hormone, 3β-Hydroxysteroid dehydrogenase(HSD), 17β-HSD, and elevated cholesterol); and testicular histopathological and morphometric disturbances. Maternal supplementation of ALA was found to alleviate all the CYT-induced reproductive disruptions. Significance: The present work accentuates the beneficial actions of ALA against CYT-induced impairment in reproductive development and functions by combating disruptions in oxidative balance, steroidogenesis, spermatogenesis, and testicular histological aberrations. However, future experimental and clinical studies are warranted to explore the molecular mechanisms involved in the ALA's protection against prenatal CYT-induced testicular injury. [ABSTRACT FROM AUTHOR]

Purpose: Cough represents a natural mechanism that plays an important defensive role in the respiratory tract, but in some conditions, it may become persistent, nonproductive, and harmful. In general, refractory chronic cough (RCC) occurs in about 20% of individuals; hence, we aimed to assess the presence of altered gut–lung communication in RCC patients through a compositional and functional characterization of both gut (GM) and oral microbiota (OM). Methods: 16S rRNA sequencing was used to characterize both GM and OM composition of RCC patients and healthy controls (HC). PICRUST2 assessed functional changes in microbial communities while gas chromatography was used to evaluate fecal short-chain fatty acid levels and serum-free fatty acid (FFA) abundances. Results: In comparison with HC, RCC patients reported increased saliva alpha-diversity and statistically significant beta-diversity in both GM and OM. Also, a, respectively, significant increased or reduced Firmicutes/Bacteroidota ratio in stool and saliva samples of RCC patients has been shown, in addition to a modification of the abundances of several taxa in both GM and OM. Moreover, a potential fecal over-expression of lipopolysaccharide biosynthesis and lipoic acid metabolism pathways and several differences in serum FFA levels have been reported in RCC patients than in HC. Conclusion: Since differences in both GM and OM of RCC patients have been documented, these findings could provide new information about RCC pathogenesis and also pave the way for the development of novel nutritional or pharmacological interventions for the management of RCC through the restoration of eubiotic gut–lung communication. [ABSTRACT FROM AUTHOR]

Rationale: Alpha-lipoic acid is an essential cofactor for aerobic metabolism and acts as a potent antioxidant in the body. It has been shown that acute exposure to methamphetamine induces oxidative stress, which is responsible for severe cognitive deficits in animals. The hippocampus plays a crucial role in the processing of memory and anxiety-like behavior. Objectives: In this study, preventive effect of the alpha-lipoic acid on memory impairment in methamphetamine-induced neurotoxicity was investigated. Methods: Wistar male rats (200–220 g) were allocated to five groups (seven rats in each group): (1) saline + saline, (2) saline + vehicle (sunflower oil as alpha-lipoic acid solvent), (3) methamphetamine + vehicle, (4) methamphetamine + alpha-lipoic acid 10 mg/kg, and (5) methamphetamine + alpha-lipoic acid 40 mg/kg. Rats received intraperitoneal methamphetamine repeatedly (2 × 20 mg/kg, 2 h interval). Alpha-lipoic acid was injected 30 min, 24 h, and 48 h after the last injection of methamphetamine. The passive avoidance test and open field were used for evaluation of memory retrieval and anxiety, respectively. After behavioral test, rats were anesthetized, their brains were extracted, and after preparing hippocampal homogenates, malondialdehyde (MDA) level, catalase, and superoxide dismutase (SOD) activities were evaluated. Results: Statistical analysis showed that injection of saline or sunflower oil had no significant effect on anxiety, memory, or oxidative stress markers. Methamphetamine induced memory impairment, increased anxiety-like behavior and MDA level, but it reduced catalase and SOD activity. Treatment with alpha-lipoic acid decreased MDA, increased catalase and SOD activity, and also prevented memory impairment and anxiety-like behavior. Our results showed that alpha-lipoic acid protected the hippocampus from oxidative stress by elevating SOD and CAT activities and reduced memory impairment following acute methamphetamine injection. These findings suggest that alpha-lipoic acid may have a protective effect against the adverse effects of methamphetamine exposure on the hippocampus. Therefore, the current data indicated that ALA can reduce oxidative stress predominantly by its antioxidant property. [ABSTRACT FROM AUTHOR]

Background: Insulin autoimmune antibody syndrome is an uncommon cause of hypoglycemia in non-diabetic individuals. We report a case of alpha-lipoic acid-induced insulin autoimmune antibody syndrome. Case report: A 40-year-old non-diabetic female presented with unresponsiveness due to severe hypoglycemia. Investigations revealed high fasting insulin levels, elevated C-peptide, and positive anti-insulin antibodies. Further history revealed recent ingestion of alpha-lipoic acid supplements. She was diagnosed with alpha-lipoic acid-induced insulin autoimmune antibody syndrome and managed with symptomatic measures and steroids. Conclusions: This case highlights the importance of recognizing drug-induced insulin autoimmune antibody syndrome as a potential cause of hypoglycemia in non-diabetic individuals, especially in the context of recent supplement or medication use. [ABSTRACT FROM AUTHOR]

The effect of thioxypine (2-ethyl-6-methylpyridinol-3-yl thioctate) and its acyl and alcohol components on the duration of behavioral despair (BD) in the mouse tail suspension test according to L. Steru, et al. and the forced swimming test of mice and rats according to R. Porsolt, et al. was studied. Amitriptyline (a reference antidepressant) was used as a reference BD-contractor. The impact of the substances being studied on the behavior of mice in the open-field test was additionally evaluated to provide a control of false-positive and false-negative results. Ambiguous effects of the studied substances on the duration of BD were revealed. The direction of the changes depended on the stress generated in the used tests. Thioxypine, unlike its free components, was shown to lack thymoanaleptic potential although it had a sedative effect due to its acyl (thioctyl) fragment. The prospects of further studying the psychotropic action of thioxypine with an emphasis on identification of its possible tranquilizing and antipsychotic activity were considered. [ABSTRACT FROM AUTHOR]

This study aimed to investigate the protective effects of usnic acid and alpha lipoic acid on changes in cellular mitogenic activity proteins in serum, liver, and kidney tissue of rats with cadmium toxicity. Cadmium (Cd) amounts in samples taken from serum, liver and kidney tissues, and Mitogen Activity Protein Kinases (MAPK), Guanosine Triphosphatase (GTPase), Nuclear Factor Kappa-B P65 (NFκBp65) and Nuclear Factor Kappa-B (NFκB) in cell and mitogenic activity proteins in liver and kidney tissues changes were evaluated. The levels of Cd in liver and kidney tissues increased significantly compared to control, whereas liver Cd levels of usnic acid (UA) group decreased. MAPK activity in liver tissues of alpha lipoic acid (ALA) group showed a statistically significant decrease compared to other groups. In contrast, liver tissues of UA group showed a significant increase compared to all other groups. Renal tissue GTPase level decreased significantly in the control group compared to the other groups, while GTPase level was increased dramatically in UA group compared to all other groups. When the levels of NF-κBp65 protein in liver tissue were compared to control, Cd increased significantly. In contrast, comparison of Cd group to UA + Cd and ALA + Cd groups showed a significant decrease in NF-κBp65 levels. Application of ALA in Cd toxicity significantly increased liver tissue NF-κB levels and decreased renal tissue NF-κB levels. In conclusion, it was determined that UA and ALA have protective effects on Cd-induced liver toxicity in rats. In contrast, UA and ALA did not have a protective effect on renal tissue. [ABSTRACT FROM AUTHOR]

The conjugation of active biomolecules provides insight into their bioreactivity, leading to many applications in biotechnology and materials science. Herein, we report L-selenocystine (SeC) bioconjugates of lipoic acid (universal antioxidant) and biotin (Vitamin-H). The SeC-bioconjugates, SeC-Biotin (1) and SeC-Lipoic acid (2) were synthesized using solid phase peptide synthesis (SPPS) method and were characterized by multinuclear 1D (1H, 13C, 77Se) and 2D (1H-1H COSY and 1H-13C TOCSY) NMR spectroscopy, ESI–MS spectrometry, and RP-HPLC. The GPx-like enzyme mimicking activity of the SeC-bioconjugates 1 and 2 has been investigated through the coupled reductase assay method for the catalytic reductions of hydrogen peroxide into water. A significant enhancement in GPx-like enzymatic activity was observed for both novel bioconjugates SeC-Biotin (1) and SeC-Lipoic acid (2) as compared to diphenyl diselenide (Ph2Se2), L-selenocystine (SeC), biotin, lipoic acid, and ebselen. [ABSTRACT FROM AUTHOR]

Purpose: Lipoyltransferase 1 (LIPT1) has been recently identified as a cuproptosis‑related gene. As a key enzyme of lipoic acid metabolism, LIPT1 has been revealed to play important roles in hereditary diseases involved with lipoic acid biosynthesis defects, while its roles in hepatocellular carcinoma (HCC) remain to be elucidated. Hence, we aimed to explore the roles and mechanisms of LIPT1 in HCC progression. Methods: The expression of LIPT1 in HCC tissues and its clinical significance for HCC were evaluated by bioinformatic analysis and in our patient cohort. The influences of LIPT1 on the growth, migration, and lipid metabolism of HCC cells were assessed in vitro. The underlying mechanisms were explored using gene set enrichment analysis (GSEA) and molecular experiments. Results: LIPT1 expression was significantly elevated in HCC tissues compared to the normal tissues, and such upregulation was associated with more malignant pathological features and poor prognosis of patients with HCC. LIPT1 silencing significantly inhibited cell proliferation, migration, and lipid content. GSEA revealed that LIPT1 upregulation was significantly associated with various cancer-associated signaling pathways, including the PI3K-AKT signaling pathway and the Wnt/β-catenin pathway. Further molecular experiments indicated that LIPT1 silencing repressed the expression of peroxisome proliferator-activated receptor gamma (PPARγ) and inactivated the AKT/GSK-3β/β-catenin signaling axis. Conclusions: Upregulation of LIPT1 is involved in metabolic dysregulation of fatty acid and poor prognosis of HCC patients, which suggests that LIPT1 plays an important role in reprogramming lipid metabolism and could act as a potential prognostic marker and therapeutic target for HCC. [ABSTRACT FROM AUTHOR]

Organosilicon compounds have shown tremendous potential in drug discovery and their synthesis stimulates wide interest. Multicomponent cross-coupling of alkenes with silicon reagents is used to yield complex silicon-containing compounds from readily accessible feedstock chemicals but the reaction with simple alkenes remains challenging. Here, we report a regioselective silylalkylation of simple alkenes, which is enabled by using a stable Ni(II) salt and an inexpensive trans−1,2-diaminocyclohexane ligand as a catalyst. Remarkably, this reaction can tolerate a broad range of olefins bearing various functional groups, including alcohol, ester, amides and ethers, thus it allows for the efficient and selective assembly of a diverse range of bifunctional organosilicon building blocks from terminal alkenes, alkyl halides and the Suginome reagent. Moreover, an expedient synthetic route toward alpha-Lipoic acid has been developed by this methodology. Multicomponent cross-coupling of alkenes with silicon reagents is used to yield complex silicon-containing compounds from readily accessible feedstock chemicals but the reaction with simple alkenes remains challenging. Here, the authors report a regioselective silylalkylation of simple alkenes, which is enabled by using a stable Ni(II) salt and an inexpensive trans-1,2-diaminocyclohexane ligand as a catalyst. [ABSTRACT FROM AUTHOR]

The effect of nanodispersions with lipoic acid and its esters on the activity of lactate dehydrogenase in neutrophils and platelets has been studied. It has been shown that nanoparticles with lipoic acid and its esters decrease the activity of lactate dehydrogenase in neutrophils and platelets 1.5–2 times, which indicates that nanodispersions containing lipoic acid and its conjugates decrease the concentration of reactive oxygen species in activated neutrophils and platelets 2–3 times. Studies on the inhibition of free radical processes in neutrophils and platelets showed that the nanoforms with lipoic acid and its esters possess an antioxidant activity. [ABSTRACT FROM AUTHOR]

The free radical chemistry of lipoic acid (LA) and dihydrolipoic acid (DHLA) intersect at the point where DHLA loses hydrogen to a good hydrogen abstracting radical, while LA reacts with strongly reducing ketyl radicals capable of donating a hydrogen atom. While aliphatic thiyl radicals have an absorbance at ~ 330 nm, the resulting radical, formally also a thiyl radical has distinct spectroscopic properties with a maximum at 385 nm, suggesting that the two sulphur centres interact strongly with each other as part of the chromophore. The reactions that form these radicals were studied by laser flash photolysis that revealed DHLA as an excellent hydrogen donor, while LA is an excellent hydrogen acceptor. The results support earlier evidence that the real antioxidant is DHLA, while LA is not; yet, the reported facile interconversion of the two molecules suggests that LA may be a better supplement, given its shelf stability, compared with a far more difficult-to-handle DHLA. [ABSTRACT FROM AUTHOR]

The present work investigated the effect of α-lipoic acid (ALA) and caffeine-loaded chitosan nanoparticles (CAF-CS NPs) on obesity and its hepatic and renal complications in rats. Rats were divided into control, rat model of obesity induced by high fat diet (HFD), and obese rats treated with ALA and/or CAF-CS NPs. At the end of the experiment, the activities of aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP) and the levels of urea, creatinine, interleukin-1β (IL-1β), and tumor necrosis factor-α (TNF-α) were determined in the sera of animals. In addition, malondialdehyde (MDA), nitric oxide (NO), and reduced glutathione (GSH) were measured in hepatic and renal tissues. Renal Na+, K+-ATPase was assessed. The histopathological changes were examined in the hepatic and renal tissues. Obese rats showed a significant increase in AST, ALT, ALP, urea, and creatinine. This was associated with a significant increase in IL-1β, TNF-α, MDA, and NO. A significant decrease in hepatic and renal GSH and renal Na+, K+-ATPase activity was recorded in obese rats. Obese rats also showed histopathological alterations in hepatic and renal tissues. Treatment with ALA and/or CAF-CS NPs reduced the weight of obese rats and ameliorated almost all the hepatic and renal biochemical and histopathological changes induced in obese rats. In conclusion, the present findings indicate that ALA and/or CAF-CS NPs offered an effective therapy against obesity induced by HFD and its hepatic and renal complications. The therapeutic effect of ALA and CAF-CS NPs could be mediated through their antioxidant and anti-inflammatory properties. [ABSTRACT FROM AUTHOR]

The utilization of digital technology has grown rapidly in the past three decades. With this rapid increase, cell phones emit electromagnetic radiation; that is why electromagnetic field (EMF) has become a substantial new pollution source in modern civilization, mainly having adverse effects on the brain. While such a topic attracted many researchers' scopes, there are still minimal discoveries made regarding chronic exposure to EMF. The extensive use of cell phones may affect children's cognition even indirectly if parents and guardians used their phones repeatedly near them. This study aims to investigate possible lipoic acid (LA) effects on cognitive functions and hippocampal structure in young male rats exposed to electromagnetic fields (EMF) emitted from multiple cell phones. Forty young male Wistar rats were randomly allocated into three groups: control, multiple cell phones-exposed and lipoic acid-treated rats. By the end of the experimental period, the Morris water maze was used as a cognitive test. The rats were sacrificed for the collection of serum and hippocampal tissue. These serum samples were then utilized for assessment of Liver function tests. The level ofglutamate, acetylcholine (Ach) and malondialdehyde (MDA) was estimated, in addition to evaluating the expression of autophagy-related protein-7 (Atg7) and Sirt1 genes. The left hippocampal specimens were used for histopathological studies. Results showed that multiple cell phone-exposed rats exhibited shorter latency time to reach the platform by the fifth day of training; additionally, there was a reduction in consolidation of spatial long-term memory. Correspondingly, there was an elevation of hippocampal Ach, glutamate, and MDA levels; accompanied by up-regulation of hippocampal Sirt1 and Atg7 gene expression. Compared to the EMF-exposed group, LA administration improved both learning and memory, this was proved by the significant decline in hippocampal MDA and Ach levels, the higher hippocampal glutamate, the downregulated hippocampal Sirt1 gene expression and the upregulated Atg7 gene expression. In conclusion, EMF exposure could enhance learning ability; however, it interfered with long-term memory consolidation shown by higher hippocampal Ach levels. Lipoic acid treatment improved both learning and memory by enhancing autophagy and hippocampal glutamate level and by the reduced Ach levels and Sirt1 gene expression. [ABSTRACT FROM AUTHOR]

Low-molecular-weight dinitrosyl iron complexes (DNICs) with thiol-containing ligands are a physiological form for deposit and transport of nitric oxide (NO) in the organism; DNICs can exhibit antioxidant and antiradical properties. It has been found that DNICs containing cysteine, glutathione and lipoic acid as ligands, decreased the rate of dihydrodamine oxidation by peroxynitrite formed during 3-morpholinonymine decomposition. Thiol (sulfhydryl) ligands are present in DNICs in the form of thiolate anions (RS−), which protects these groups from oxidation by peroxynitrite. When tert-butyl hydroperoxide was used as an oxidizer at low concentration, the protective effect of DNICs on their SH-groups was observed for complexes with lipoic acid (LA-DNIC) and with glutathione (GS-DNIC). LA-DNICs were more resistant to oxidizing agents and were a more effective peroxynitrite trap than other DNICs. DNICs associated with bovine serum albumin had a negligible protective effect on cysteine residues during oxidation by peroxynitrite and tert-butyl hydroperoxide. These results allow us to consider low-molecular-weight DNICs with thiol ligands as peroxynitrite traps and thiol residues protectors in proteins. [ABSTRACT FROM AUTHOR]

The effect of Au nanoparticles (AuNPs) on the photoluminescence (PL) of AgInS2/ZnS quantum dots (QDs) in buffer solutions was investigated. The QDs stabilized with mercaptoacetic acid and glutathione were modified by 19-bases thiolated oligonucleotides, and the AuNPs grown in citrate solution and stabilized with lipoic acid and mercaptohexanol were modified by 26-bases thiolated oligonucleotide. These oligonucleotides are not complementary to each other. The nanoobjects were placed in buffer solutions of SSC with different dilutions (0.1 × , 0.25 × , 0.5 × SSC). The PL and optical absorption (OA) spectra of prepared solutions were studied. In the buffer solutions of different dilutions, the formation of aggregates of AuNPs depends on QDs' stabilizing ligands and presence/absence of oligonucleotides on AuNPs' surface, which was detected by specific changes in the OA spectra. The degree of PL quenching also was different in solution with modified and unmodified nanoobjects. The solutions were additionally incubated at room temperature for 24 h to see the dynamic of changing in the interaction between AuNPs and QDs, one of the manifestations of this interaction was an electrolytic aggregation. It is proposed that the observed decrease of PL intensity (PLI) in solutions with unmodified nanoobjects is due to the partial absorption of excitation light by AuNPs, and the interaction between QDs and AuNPs is caused by the presence of noncomplementary oligonucleotides on their surface. [ABSTRACT FROM AUTHOR]

Chemotherapy-induced cognitive impairment (CICI) is a common complication associated with the use of chemotherapeutics. Doxorubicin (DOX) is a reactive oxygen species (ROS) producing anticancer agent capable of causing potential neurotoxic effects via cytokine-induced oxidative and nitrosative damage to brain tissues. On the other hand, alpha-lipoic acid (ALA), a nutritional supplement, is reputable for its excellent antioxidant, anti-inflammatory, and anti-apoptotic activities. Consequently, the objective of the current investigation was to examine any potential neuroprotective and memory-improving benefits of ALA against DOX-induced behavioral and neurological anomalies. DOX (2 mg/kg/week, i.p.) was administrated for 4 weeks to Sprague–Dawley rats. ALA (50, 100, and 200 mg/kg) was administered for 4 weeks. The Morris water maze (MWM) and novel objective recognition task (NORT) tests were used to assess memory function. Biochemical assays with UV–visible spectrophotometry were used to analyze oxidative stress markers [malondialdehyde (MDA), protein carbonylation (PCO)], endogenous antioxidants [reduced glutathione (GSH), catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GSH-Px)] and acetylcholinesterase (AChE) activity in hippocampal tissue. Inflammatory markers [tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and nuclear factor kappa B (NF-κB)], nuclear factor erythroid 2-related factor-2 (NRF-2) and hemeoxygenase-1 (HO-1) levels were estimated using enzyme-linked immunosorbent assay (ELISA). In addition, reactive oxygen species (ROS) levels were measured in hippocampus tissue using 2-7-dichlorofluorescein-diacetate (DCFH-DA) assay with fluorimetry. ALA treatment significantly protected against DOX-induced memory impairment. Furthermore, ALA restored hippocampal antioxidants, halted DOX-induced oxidative and inflammatory insults via upregulation of NRF-2/HO-1 levels, and alleviated the increase in NF-κB expression. These results indicate that ALA offers neuroprotection against DOX-induced cognitive impairment, which could be attributed to its antioxidant potential via the NRF-2/HO-1 signaling pathway. [ABSTRACT FROM AUTHOR]

Highlights: The gelation of hole transport layer generates a dense and uniform hole transport layer film and significantly inhibits the aggregation of lithium bis(trifluoromethane sulfonyl)imide in spiro-OMeTAD. The gelated hole transport layer confers enhanced charge carrier transport and better humidity and operational stability of perovskite solar cells. To achieve high power conversion efficiency (PCE) and long-term stability of perovskite solar cells (PSCs), a hole transport layer (HTL) with persistently high conductivity, good moisture/oxygen barrier ability, and adequate passivation capability is important. To achieve enough conductivity and effective hole extraction, spiro-OMeTAD, one of the most frequently used HTL in optoelectronic devices, often needs chemical doping with a lithium compound (LiTFSI). However, the lithium salt dopant induces crystallization and has a negative impact on the performance and lifetime of the device due to its hygroscopic nature. Here, we provide an easy method for creating a gel by mixing a natural small molecule additive (thioctic acid, TA) with spiro-OMeTAD. We discover that gelation effectively improves the compactness of resultant HTL and prevents moisture and oxygen infiltration. Moreover, the gelation of HTL improves not only the conductivity of spiro-OMeTAD, but also the operational robustness of the devices in the atmospheric environment. In addition, TA passivates the perovskite defects and facilitates the charge transfer from the perovskite layer to HTL. As a consequence, the optimized PSCs based on the gelated HTL exhibit an improved PCE (22.52%) with excellent device stability. [ABSTRACT FROM AUTHOR]

Chronic COVID syndrome is characterized by chronic fatigue, myalgia, depression and sleep disturbances, similar to chronic fatigue syndrome (CFS) and fibromyalgia syndrome. Implementations of mitochondrial nutrients (MNs) with diet are important for the clinical effects antioxidant. We examined if use of an association of coenzyme Q10 and alpha lipoic acid (Requpero®) could reduce chronic covid symptoms. The Requpero study is a prospective observational study in which 174 patients, who had developed chronic-covid syndrome, were divided in two groups: The first one (116 patients) received coenzyme Q10 + alpha lipoic acid, and the second one (58 patients) did not receive any treatment. Primary outcome was reduction in Fatigue Severity Scale (FSS) in treatment group compared with control group. complete FSS response was reached most frequently in treatment group than in control group. A FSS complete response was reached in 62 (53.5%) patients in treatment group and in two (3.5%) patients in control group. A reduction in FSS core < 20% from baseline at T1 (non-response) was observed in 11 patients in the treatment group (9.5%) and in 15 patients in the control group (25.9%) (p < 0.0001). To date, this is the first study that tests the efficacy of coenzyme Q10 and alpha lipoic acid in chronic Covid syndrome. Primary and secondary outcomes were met. These results have to be confirmed through a double blind placebo controlled trial of longer duration. [ABSTRACT FROM AUTHOR]

Lipoic acid is an essential enzyme cofactor in central metabolic pathways. Due to its claimed antioxidant properties, racemic (R/S)-lipoic acid is used as a food supplement but is also investigated as a pharmaceutical in over 180 clinical trials covering a broad range of diseases. Moreover, (R/S)-lipoic acid is an approved drug for the treatment of diabetic neuropathy. However, its mechanism of action remains elusive. Here, we performed chemoproteomics-aided target deconvolution of lipoic acid and its active close analog lipoamide. We find that histone deacetylases HDAC1, HDAC2, HDAC3, HDAC6, HDAC8, and HDAC10 are molecular targets of the reduced form of lipoic acid and lipoamide. Importantly, only the naturally occurring (R)-enantiomer inhibits HDACs at physiologically relevant concentrations and leads to hyperacetylation of HDAC substrates. The inhibition of HDACs by (R)-lipoic acid and lipoamide explain why both compounds prevent stress granule formation in cells and may also provide a molecular rationale for many other phenotypic effects elicited by lipoic acid. Lipoic acid is a food supplement and approved neuropathy drug but lacks known molecular targets. Here, Lechner et al. employ chemoproteomic target deconvolution to demonstrate that (R)- but not (S)-lipoic acid stereoselectively inhibits histone deacetylases at physiologically achievable doses. [ABSTRACT FROM AUTHOR]

The ester of thioctic (α-lipoic) acid and 2-ethyl-6-methyl-3-hydroxypyridine was synthesized. The toxicity decreased while the antihypoxic activity simultaneously increased for an equimolar mixture of thioctic acid and 2-ethyl-6-methyl-3-hydroxypyridine after they were combined into 2-ethyl-6-methylpyridinol-3-yl thioctate (laboratory name thioxypine). The tolerance to asphyxia increased by 51%; to hypercapnic hypoxia, by 47% after intraperitoneal (i.p.) administration of thioxypine at a dose of 145 μmol/kg. Such a combination of effects corresponded to the formal criteria for classifying thioxypine as an antihypoxant. A fourfold reduction in the dosage of thioxypine (to 36.25 μmol/kg) reduced the resistance to histotoxic hypoxia by 32%. The synthesized ether did not affect the resistance to hemic hypoxia. [ABSTRACT FROM AUTHOR]

Diabetes mellitus (DM) is a chronic syndrome involving neuropathic pain. Increased oxidative stress in DM is assumed to increase free reactive oxygen radicals (ROS) and causes diabetic damage. The sciatic nerve (ScN) and dorsal root ganglion (DRG) both contain high levels of the TRPV1 channel, which is triggered by capsaicin and ROSs and results in increased Ca2+ entry into the neurons. Alpha-lipoic acid (ALA) is considered an important part of the antioxidant system. To better characterize the protective effects of ALA on the DM-induced neuronal through TRPV1 modulation, we investigated the role of ALA on DM-induced neuropathic pain, oxidative ScN, and DRG damage in diabetic rats. Forty adult Wistar albino female rats were divided into four groups as control, ALA (50 mg/kg for 14 days), streptozotocin (STZ and 45 mg/kg and single dose), and STZ + ALA. Rats were used for the pain tests. After obtaining the DRGs and ScN, they were used for plate reader, patch-clamp, and laser confocal microscope analyses. We observed the modulator role of ALA on the thresholds of mechanical withdrawal pain (von Frey test) and hot sensitivity pain (hot plate test) in the STZ + ALA group. The treatment of ALA decreased STZ-induced increase of TRPV1 current densities, intracellular free Ca2+ concentrations (Fura-2 and Fluo − 3/AM), ROS, caspase 3, caspase 9, mitochondrial membrane potential, and apoptosis values in the ScN and DRG neurons, although its treatment induced the increase of cell viability and body weight gain. The treatment of ALA acted a neuroprotective role on the TRPV1 channel stimulation-mediated Ca2+ influx, neuropathic pain, and neuronal damage in diabetic rats. The neuroprotective role of ALA treatment can be explained by its modulating the TRPV1 channel activity, intracellular Ca2+ increase-induced oxidative stress, and apoptosis. [ABSTRACT FROM AUTHOR]

We propose the photopolymerization of lipoic acid (LA) as an novel approach to produce a cross-linked polymeric matrix of lipoic acid monomers (PALA) which helps to control the size of plasmonic gold nanostructures when using 3,3,6,8-tetramethyl-1-tetralone as the photo-initiator for the reduction of Au(III) to Au0. A complete characterization of the polymer is included, and the dual behaviour of LA as an in situ stabilizer and reducing agent is investigated. These findings are relevant to the understanding of the photochemical transformation of this biologically relevant compound and would benefit the increasing use of LA and PALA for the synthesis of various nanomaterials. [ABSTRACT FROM AUTHOR]

Heat stress (HS) is a long-standing hurdle that animals face in the living environment. Alpha-lipoic acid (ALA) is a strong antioxidant synthesized by plants and animals. The present study evaluated the mechanism of ALA action in HS-induced early porcine parthenotes development. Parthenogenetically activated porcine oocytes were divided into three groups: control, high temperature (HT) (42 °C for 10 h), and HT + ALA (with 10 µM ALA). The results show that HT treatment significantly reduced the blastocyst formation rate compared to the control. The addition of ALA partially restored the development and improved the quality of blastocysts. Moreover, supplementation with ALA not only induced lower levels of reactive oxygen species and higher glutathione levels but also markedly reduced the expression of glucose regulatory protein 78. The protein levels of heat shock factor 1 and heat shock protein 40 were higher in the HT + ALA group, which suggests activation of the heat shock response. The addition of ALA reduced the expression of caspase 3 and increased the expression of B-cell lymphoma-extra-large protein. Collectively, this study revealed that ALA supplementation ameliorated HS-induced apoptosis by suppressing oxidative and endoplasmic reticulum stresses via activating the heat shock response, which improved the quality of HS-exposed porcine parthenotes. [ABSTRACT FROM AUTHOR]

A method for the synthesis of a conjugate of 4-substituted phenylterpyridine and lipoic acid, containing a triethylene glycol linker group between the terpyridine and sulfur-containing fragments, has been developed. A coordination compound of the resulting terpyridine with Rh(III) was obtained. Cyclic voltammetry was used to explore the ability of the synthesized ligand and its rhodium complex to be chemisorbed on the surface of gold electrodes to form an Au–S bond. [ABSTRACT FROM AUTHOR]

Polyurethanes (PUs) are a polymer material with a wide range of applications and excellent mechanical properties. In this work, a modified polyurethane coating with the self-healing function is developed via the reaction between polytetrahydrofuran (PTMG), 2,4-toluene diisocyanate (TDI) and α-lipoic acid. The coatings are characterized by SEM and FTIR. The protection of the prepared coating for copper in 3 wt.% NaCl solution is investigated by the electrochemical measurements and the surface self-healing tests. The coating has stable protection from corrosion of the copper substrate in corrosive medium and shows a good self-healing ability. The healing behavior in morphology and corrosion resistance can be observed when heated above 60°C. [ABSTRACT FROM AUTHOR]

Mitochondrial fatty acid synthesis (mtFAS) is essential for respiratory function. MtFAS generates the octanoic acid precursor for lipoic acid synthesis, but the role of longer fatty acid products has remained unclear. The structurally well-characterized component of mtFAS, human 2E-enoyl-ACP reductase (MECR) rescues respiratory growth and lipoylation defects of a Saccharomyces cerevisiae Δetr1 strain lacking native mtFAS enoyl reductase. To address the role of longer products of mtFAS, we employed in silico molecular simulations to design a MECR variant with a shortened substrate binding cavity. Our in vitro and in vivo analyses indicate that the MECR G165Q variant allows synthesis of octanoyl groups but not long chain fatty acids, confirming the validity of our computational approach to engineer substrate length specificity. Furthermore, our data imply that restoring lipoylation in mtFAS deficient yeast strains is not sufficient to support respiration and that long chain acyl-ACPs generated by mtFAS are required for mitochondrial function. Mitochondrial fatty acid synthesis (mtFAS) generates the precursor for lipoic acid synthesis, but the role of longer fatty acid products has remained unclear. Here, the authors generated an engineered variant of human 2E-enoyl-ACP reductase (MECR) of mtFAS to study the role of long chain fatty acids. [ABSTRACT FROM AUTHOR]

Accommodation is the change in dioptric power of the eye. It is a dynamic process that allows focusing on an object at all distances. In order to focus sharply, three physiological responses, known as the triad of accommodation, are produced by a change in pupil size, a change in shape and position of the lens, and ocular convergence. This is modulated by the autonomic nervous system, mainly the parasympathetic nervous system. Presbyopia is a refractive condition that occurs with aging, usually manifesting around 40–50 years of age, and is a result of the loss of accommodation in the eye, causing loss of visual performance when focusing on objects placed at different distances, starting with near vision. Glasses, contact lenses, surgical approaches and now pharmacological treatments are accepted methods of treating presbyopia. Pharmacological treatment is a promising new noninvasive option for treating presbyopia. Currently there are three pharmacological approaches to the treatment of presbyopia. The first one aims to produce miosis and, from a pinhole effect, increase depth of focus, and therefore improve uncorrected near visual acuity (UNVA). The second one addresses rehabilitating accommodation in a binocular way, allowing good vision at all distances. Finally, the third strategy uses lipoic acid to restore the lost elasticity of the lens. All of these pharmacological treatments are topical non-invasive eyedrops, with no serious adverse effects having been reported with any of the strategies, and require the right patient selection process to fulfill expectations and needs. The aim of this article is to provide an update on recent advances in this field. [ABSTRACT FROM AUTHOR]

Objective: The current study evaluates the effect of metformin (MET) and /or alpha lipoic acid (ALA) on hypothyroidism and its adverse effects on the cardiac, renal, and, hepatic functions in rats. Materials and methods: Rats were divided into five groups: control, rat model of hypothyroidism induced by propylthiouracil (PTU), rat model of hypothyroidism treated with MET, rat model of hypothyroidism treated with ALA, and rat model of hypothyroidism treated with MET and ALA. At the end of the experiment, body weight gain was determined and the blood samples were collected from orbital plexus to measure the serum levels of thyroxine (T4), triiodothyronine (T3) and thyroid stimulating hormone (TSH) by ELISA, glucose level, the activities of lactate dehydrogenase (LDH), creatine kinase MB (CK-MB), aspartate aminotransferase (AST), alanine aminotransferase (ALT), and alkaline phosphatase (ALP), and the levels of urea and creatinine spectrophotometrically. Results: Rat model of hypothyroidism revealed a significant decrease in T4 (p < 0.001) and T3 (p < 0.001) and a significant increase in TSH (p < 0.005). This was accompanied by a significant decrease in the body weight gain (p < 0.025) and a significant increase in LDH (p < 0.001), CK-MB (p < 0.001) AST (p < 0.01), ALT (p < 0.016), ALP (p < 0.001), glucose (p < 0.001), urea (p < 0.001) and creatinine (p < 0.001). MET restored T4, T3 and TSH to control values. Treatment with ALA restored T3 and TSH levels. Treatment with Met and /or ALA reduced the levels of glucose, urea and creatinine and the activities of LDH, CK-MB, AST, ALT, and ALP to control-like values. Only ALA improved the reduced body weight gain induced by hypothyroidism. Conclusion: The present findings indicate the ameliorative effects of MET and /or ALA on hypothyroidism and its adverse effects on cardiac, renal and hepatic functions. [ABSTRACT FROM AUTHOR]

Background: This investigation was performed to assess the effects of alpha-lipoic acid (ALA) supplementation on psychological status and markers of inflammation and oxidative damage in patients with type 2 diabetes mellitus (T2DM) and coronary heart disease (CHD). Methods: This randomized, double-blind, placebo-controlled trial was performed in 60 patients with T2DM and CHD, aged 45–85 years. Patients were randomized into two groups to receive either 600 mg/day ALA (n = 30) or placebo (n = 30) for 12 weeks. Results: ALA supplementation significantly decreased Beck Depression Inventory index (BDI) (-5.1 ± 3.5 vs. -1.1 ± 4.8, P = 0.001) when compared with the placebo. ALA supplementation resulted also in a significant reduction of serum high sensitivity C-reactive protein (hs-CRP) (-0.8 ± 1.4 vs. +0.5 ± 0.6 mg/L, P < 0.001) and malondialdehyde (MDA) (-0.3 ± 0.2 vs. -0.1 ± 0.3 µmol/L, P = 0.003), and a significant increase in plasma total antioxidant capacity (TAC) levels (+ 26.8 ± 36.0 vs. -4.6 ± 43.4 mmol/L, P = 0.007) when compared with the placebo. ALA intake upregulated transforming growth factor beta (TGF-β) (P = 0.03) and downregulated gene expression of interleukin-1 (IL-1) (P = 0.001) in peripheral blood mononuclear cells of patients with T2DM and CHD as well. Conclusions: ALA supplementation for 12 weeks in patients with T2DM and CHD had beneficial effects on BDI, hs-CRP, TAC, MDA values, and gene expression of IL-1 and TGF-β. [ABSTRACT FROM AUTHOR]

As a hydroxymethylglutaryl coenzyme A (HMG-CoA) reductase inhibitor, Fluvastatin (FLV) is used for reducing low-density lipoprotein (LDL) cholesterol as well as to prevent cardiovascular problems. FLV showed cell line cytotoxicity and antitumor effect. Melittin (MEL) exhibits antineoplastic activity and is known to be promising as a therapeutic option for cancer patients. The aim of this work was to investigate the combination of FLV with MEL loaded hybrid formula of phospholipid (PL) with alpha lipoic acid (ALA) nanoparticles to maximize anticancer tendencies. This study examines the optimization of the prepared formulation in order to minimize nanoparticles size and maximize zeta potential to potentiate cytotoxic potentialities in colon cancer cells (Caco2), cell viability, cell cycle analysis and annexin V were tested. In addition to biological markers as P53, Bax, bcl2 and Caspase 3 evaluation The combination involving FLV PL ALA MEL showed enhanced cytotoxic potentiality (IC50 = 9.242 ± 0.35 µg/mL), about twofold lower, compared to the raw FLV (IC50 = 21.74 ± 0.82 µg/mL). According to studies analyzing cell cycle, optimized FLV PL ALA MEL was found to inhibit Caco2 colon cancer cells more significantly than other therapeutic treatments, wherein a higher number of cells were found to accumulate over G2/M and pre-G1 phases, whereas G0/G1/S phases witnessed the accumulation of a lower number of cells. The optimized formulation may pave the way for a novel and more efficacious treatment for colon cancer. [ABSTRACT FROM AUTHOR]

Rationale: Alpha lipoic acid is known to reverse NMDA receptor hypofunction in addition to dopamine receptor blockade activity. It also enhances neurotrophic factors and has antioxidant potential. These properties combined together may be beneficial for treatment-resistant schizophrenia (TRS). Objectives: This study evaluates the effect of alpha lipoic acid (ALA) on psychopathological scores (positive, negative, cognitive), neurotrophic factors and oxidative stress in TRS. Methods: A pilot randomized double-blind placebo-controlled parallel design trial was conducted in 20 patients with TRS. After initial screening, participants were randomized into test (add-on ALA) and control (add-on placebo) groups. After recruitment, clinical evaluations with scale for assessment of positive symptoms and negative symptoms (SAPS and SANS), schizophrenia cognitive rating scale (SCoRS), UKU side effect rating scale were done. Serum levels of BDNF, MDA, and GSH were estimated. Patients were followed up for 8 weeks, and clinical and biochemical evaluations were repeated. Adherence to medication was evaluated at follow-up. Results: A significantly greater improvement was found in SANS score in the test group when compared to control (Mann–Whitney U = 17.0; p = 0.021), whereas there was no significant improvement in SAPS score (Mann–Whitney U = 41.5; p = 0.780). A significant increase in BDNF levels was observed in the control group when compared to ALA (U = 20.0; p = 0.041). No significant differences were found between the test and control groups in serum MDA (U = 30.0; p = 0.221), serum GSH (U = 40.0; p = 0.683), and medication adherence rating scale (MARS) scores (U = 44.0; p = 0.934). Conclusions: ALA supplementation improved psychopathology and decreased oxidative stress in patients with TRS. This study thus shows the potential of adjunctive ALA in TRS. Trial registration: The study was prospectively registered in Clinical Trial Registry of India (CTRI/2020/03/023707 dated 02.03.2020). [ABSTRACT FROM AUTHOR]

As a widely used anti-tumor anthracycline, the accumulation of Doxorubicin (DOX) in body causes irreparable cardiomyocyte damage and therefore is limited in clinical application. Strategies to prevent from DOX-associated cardiotoxicity are urgent for patients who undergo DOX-based chemotherapy. Since oxidative stress injury being the major reason for myocardial toxicity of DOX, here we demonstrated that, Alpha-lipoic acid (ALA), which is a reductive agent, plays a cardioprotective role in attenuating DOX-induced cardiotoxicity by inhibiting pyruvate dehydrogenase kinase 4 (PDK4) expression. In vivo, the beneficial effect of ALA was evidenced by increased survival rate, mechanical contraction, and oxidative phosphorylation, while decreased reactive oxidative species (ROS) and apoptosis. In vitro, PDK4 overexpression remarkably increased DOX-induced apoptosis and ROS production in H9C2 cells. Notably, the protective effect of ALA was abrogated by PDK4 overexpression. We further used PDK4 knockout mice to identify the role of PDK4 in DOX-induced cardiotoxicity. Results elicited that PDK4 deficiency showed a consistent effect in protecting DOX cardiotoxicity as ALA treatment, which was evidenced by restored redox homeostasis and mitochondrial metabolism, finally inhibited myocardial injury. In conclusion, the cardioprotective role of ALA against DOX cardiotoxicity was dependent on PDK4-mediated regulation of oxidative stress and mitochondria metabolism. [ABSTRACT FROM AUTHOR]

We present three classes of chemical zymogens established around the protein cysteinome. In each case, the cysteine thiol group was converted into a mixed disulfide: with a small molecule, a non-degradable polymer, or with a fast-depolymerizing fuse polymer (ZLA). The latter was a polydisulfide based on naturally occurring molecule, lipoic acid. Zymogen designs were applied to cysteine proteases and a kinase. In each case, enzymatic activity was successfully masked in full and reactivated by small molecule reducing agents. However, only ZLA could be reactivated by protein activators, demonstrating that the macromolecular fuse escapes the steric bulk created by the protein globule, collects activation signal in solution, and relays it to the active site of the enzyme. This afforded first-in-class chemical zymogens that are activated via protein-protein interactions. We also document zymogen exchange reactions whereby the polydisulfide is transferred between the interacting proteins via the "chain transfer" bioconjugation mechanism. Reversible on/off switches for enzyme activity are foundational in nature but are challenging to design using tools of synthetic chemistry. Here the authors design chemical zymogens amenable for activation via biomolecular interactions. [ABSTRACT FROM AUTHOR]

In this study, we assessed the possibility of using portable laser Doppler flowmeters for determining the state of the blood microcirculatory system in upper and lower limbs of diabetic patients during the treatment course with intravenous α-lipoic acid infusions. A series of experimental studies were conducted in a cohort of ten inpatients with a confirmed diagnosis of type 2 diabetes mellitus. The state of peripheral blood flow of patients was assessed during 5 days on which they received daily doses of intravenous α-lipoic acid infusions. The values of the microcirculation and nutritive blood flow indices, as well as the bypass index, were assessed. To obtain a more extensive analysis, the patients' measurement results were compared with those of the control group composed of ten conditionally healthy volunteers of similar age. To determine changes in the regulatory mechanisms for the microcirculatory bed, we applied the amplitude-spectrum analysis of microvascular blood flow oscillations, using the mathematical tool of wavelet transform. We determined the changes in the index of blood microcirculation and the parameters of microcirculatory blood flow distribution into nutritive and shunt pathways, as well as the differences between these changes in upper and lower limbs. This approach is believed to become prospective as a pharmacotherapy efficacy assessment method based on responses of the system of blood microcirculation. [ABSTRACT FROM AUTHOR]

Lipoic acid (α-LA) (1,2-dithiolane3-pentanoic acid (C8H14O2S2) is also called thioctic acid with an oxidized (disulfide, LA) and a reduced (di-thiol: dihydro-lipoic acid, DHLA) form of LA. α-LA is a potent anti-oxidative agent that has a significant potential to treat neurodegenerative disorders. α-LA is both hydrophilic and hydrophobic in nature. It is widely distributed in plants and animals in cellular membranes and in the cytosol, which is responsible for LA's action in both the cytosol and plasma membrane. A systematic literature review of Bentham, Scopus, PubMed, Medline, and EMBASE (Elsevier) databases was carried out to understand the Nature and mechanistic interventions of the α-Lipoic acid for central nervous system diseases. Moreover, α-LA readily crosses the blood-brain barrier, which is a significant factor for CNS activities. The mechanisms of α-LA reduction are highly tissue-specific. α-LA produces its neuroprotective effect by inhibiting reactive oxygen species formation and neuronal damage, modulating protein levels, and promoting neurotransmitters and anti-oxidant levels. Hence, the execution of α-LA as a therapeutic ingredient in the therapy of neurodegenerative disorders is promising. Finally, based on evidence, it can be concluded that α-LA can prevent diseases related to the nervous system. [ABSTRACT FROM AUTHOR]

Background: Prevention of lethal ventricular arrhythmias induced by myocardial ischemia/reperfusion (I/R) in diabetic patients is the major goal of cardioprotective strategies. Here, we aimed to examine the anti-arrhythmic effect of ischemic postconditioning (IPostC) and alpha-lipoic acid (ALA) in myocardial I/R injury of type-II diabetic rats, focusing on the involvement of connexin-43 and nitric oxide (NO) in this context. Methods: Diabetes (duration of 12 weeks) was induced by high-fat diet and low dose of streptozotocin in thirty male Wistar rats (12 weeks old, 200–250 g). After mounting the hearts on the Langendorff apparatus, I/R was induced by the ligation of left anterior descending coronary artery for 35 min, and reperfusion for 60 min. ALA (100 mg/kg/day) was administered orally in diabetic rats for five weeks before I/R. IPostC was applied immediately at early reperfusion. The arrhythmias were evaluated according to the Lambeth convention. Connexin-43 expression and NO levels were assessed by western blotting and Griess calorimetric method, respectively. Results: IPostC could not significantly decrease the number, duration, and incidence of premature ventricular contraction, ventricular tachycardia, and ventricular fibrillation, also the severity of arrhythmias in diabetic hearts. However, IPostC in combination with ALA-preconditioning significantly decreased the above mentioned parameters compared with untreated or monotherapies-received diabetic rats (P < 0.05 to P < 0.001). Furthermore, this combination therapy significantly increased connexin-43 expression and NO levels, compared with untreated diabetic rats (P < 0.01). Conclusion: Preconditioning with ALA restored anti-arrhythmic effect of IPostC in diabetic hearts. Increased connexin-43 expression and NO levels may be the key players in this cardioprotection. [ABSTRACT FROM AUTHOR]

The kinetics of lipoic acid adsorption on the surface of silver is studied by the methods of quartz crystal microbalance and wetting. The multilayer nature of adsorption is established. The optimal conditions for the formation of a mono- and bilayer of lipoic acid on a solid surface are determined. The results obtained make it possible to predict the use of silver nanoparticles as carriers of lipophobic drugs in biomedical applications. [ABSTRACT FROM AUTHOR]

Silver nanoparticles (AgNPs) are commonly utilized in medicine. However, they have negative effects on the majority of organs, including the reproductive system. AgNPs were reported to be able to reach the testicular tissues due to their nano size, which allows them to pass through blood-testicular barriers. The goal of this study was to see if alpha-lipoic acid (LA) or Ginkgo biloba (GB) might protect adult rat testes after intraperitoneal injection of AgNPs. Forty male healthy adult Wister albino rats were randomly assigned to four groups: control, AgNPs-intoxicated group intraperitoneally injected AgNPs 50 mg/kg b.w, 3 times a week; LA + AgNPs group intoxicated with AgNPs and orally gavaged with 100 mg LA/kg b.w; and GB + AgNPs group injected with AgNPs and orally given GB extract 120 mg/kg b.w for 30 consecutive days. Biochemical changes (testosterone, ACP, and prostatic acid phosphatase), oxidative indices, mRNA expression of proapoptotic (BAX) and anti-apoptotic (BCL-2) biomarkers, histological, and immunohistochemical changes in testicular tissues were investigated. Significant decrease in serum testosterone level and elevation in ACP and PACP enzyme activity in AgNPs-treated rats. As well, there were lowering in tGSH, GSH GR, GPx, and elevation in MDA and GSSG values. AgNPs-exposed rats expressed downregulation of testicular thirodexin-1 (Txn-1), transforming growth factor-1β (TGF-1β), anti-apoptotic (BCL-2), and upregulaion of proapoptotic biomarkers (BAX) mRNA expressions. Strong positive action to BAX and lowering the action of Ki-67 antibody were observed. Because of their antioxidant, anti-inflammatory, and anti-apoptotic properties, cotreatment with LA or GB could be beneficial in reducing the harmful effects of AgNPs on the testicles. [ABSTRACT FROM AUTHOR]