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Thiamine-responsive megaloblastic anemia (TRMA) syndrome is a rare syndrome with an autosomal recessive manner that develops due to a mutation in the SLC19A2gene. SLC19A2 encodes the highaffinity thiamine transport protein 1 (THTR1), which mediates the active transport of thiamine. The classical triad consists of megaloblastic anemia, sensorineural hearing loss, and non-autoimmune diabetes. Apart from this, ophthalmological, cardiological, and neurological findings have also been described. We present a case of thiamine-responsive megaloblastic anemia (TRMA) syndrome diagnosed in an adult with a novel mutation in the SLC19A2 gene. This 38-year-old female patient, a third child from a consanguineous marriage, presented with the classic TRMA triad: sensorineural deafness, megaloblastic anemia, and autoimmune diabetes. Starting thiamine treatment is essential in reducing the devel opmen t/pro gress ion of some complications; it is crucial to increase awareness of the disease and make an early diagnosis. [ABSTRACT FROM AUTHOR]

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]

Maize (Zea mays L.) is highly sensitive to salt stress, which poses a threat to its production, especially with predicted increases in salinity due to climate change. Enhancing salt tolerance in maize is critical to mitigating these adverse effects, sustaining its production, and ensuring global food security. This study aimed to evaluate the effects of exogenously applied lipoic acid or Si, alone or in integration with soil application of vermicomposttea on physio-biochemical components, antioxidant defense systems, growth, and yield of maize plants exposed to salt stress. The application of vermicompost-tea was carried out as a soil treatment incorporated into irrigation water at a concentration of 200 L ha-1, and administered in three equal doses in irrigation water within the last 10 min of drip irrigation. Silicon was applied at a rate of 6 mM using potassium silicate and lipoic acid was applied at 0.1 mM. Silicon and lipoic acid were applied three times at 25, 40, and 55 d after planting. The results indicated that the integrative application of soil-based vermicompost-tea with exogenously applied Si or lipoic acid significantly enhanced all studied parameters. Specifically, the combination of Si with vermicomposttea exhibited the highest improvement percentage compared to untreated control in chlorophyll a (60.3%), chlorophyll b (72.7%), carotenoids (69.9%), net photosynthetic rate (111%), transpiration rate (134%), stomatal conductance (129.5%), relative water content (28.4%), membrane stability index (44.3%), N (33.4%), P (71.9%), K (39.7%), Ca (89.9%), K/Na (81.2%), total soluble sugars (63.7%), proline (60.1%), ascorbate (44.4%), glutathione (83.5%), and α-tocopherol (72.1%). These positive effects were reflected in enhancing yield traits under salt-affected soil conditions by enhancing plant height (25.1%), number of grains per row (43.3%), number of rows per ear (26.7%), 1000-grain weight (25.9%), grain yield (45.4%), and biological yield (42.8%) compared to untreated control. [ABSTRACT FROM AUTHOR]

Sustainable underwater adhesives have drawn much interest in promising applications and environmental engineering. However, developing a convenient strategy to combine recyclability and underwater adhesion into adhesive materials remains a formidable challenge. In this work, a degradable and closed‐loop recyclable underwater adhesive tackifier is designed by nucleotide, via the ring‐opening polymerization of thioctic acid in the presence of 5′‐adenosine monophosphate and methacrylatoethyl trimethyl ammonium chloride. The nucleotide‐tackified adhesives present an excellent underwater adhesion for various materials, tissues, and on‐demand detachment adhesion behavior. The underwater adhesives demonstrate reusability, degradability, and closed‐loop recyclability of dual monomers of thioctic acid and 5′‐adenosine monophosphate. Interestingly, the waste residues of the underwater adhesives demonstrate processability and can be employed again in the construction of tough adhesive interfaces in both air and underwater, with further expanding sustainability. It is envisioned that the strategy of nucleotide‐tackified sustainable underwater adhesives would offer promising insights for advancing sustainable and recyclable adhesive materials. [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]

Lithium–sulfur (Li–S) batteries possess high theoretical energy density, whereas the shuttle effect of polysulfides and the uncontrollable lithium (Li) dendrites seriously reduce the reversible capacity and cycling lifespan. Constructing an interphase to address the issues in both the cathode and anode simultaneously is significant but still challenging. In this study, a strategy of functionalizing commercial polypropylene (PP) separators is proposed by in situ poly(thioctic acid) (PTA) polymerization. Compared with the conventional separator modifications, the ring‐opening polymerization methodology initiated by heat is more facile and environment‐friendly without changing the nanostructures among the porous separators. On the cathode side, the PTA‐coated separator (PTA‐PP) blocks the shuttle of polysulfides through the electrostatic interaction. On the anode side, the PTA‐coated generates a lithium fluoride (LiF)‐rich solid electrolyte interface (SEI), identified by cryo‐transmission electron microscopy (cryo‐TEM), to accelerate the Li+ diffusion and inhibit the growth of Li dendrites. Due to the interphases constructed by the PTA‐PP separator, the Li–S cells exhibit excellent long‐term cycling in which the capacity retention rate is more than 76% after 700 cycles at 0.5 C. The in situ elaborate modification strategy may provide insights into the high‐performance separator design to promote the potentially large‐scale applications of Li–S batteries. [ABSTRACT FROM AUTHOR]

Age-related macular degeneration (AMD) is both a poorly understood and devastating disease. Here, we analyze the physico-chemical forces at stake, including osmolarity, redox shift, and pressure due to inflammation. Hyperosmolarity plays a key role in diseases of the anterior segment of the eye such as glaucoma, cataracts or dry eyes, and corneal ulceration. However, its role in macular degeneration has been largely overlooked. Hyperosmolarity is responsible for metabolic shifts such as aerobic glycolysis which increases lactate secretion by Muller cells. Increased osmolarity will also cause neoangiogenesis and cell death. Because of its unique energetic demands, the macula is very sensitive to metabolic shifts. As a proof of concept, subretinal injection of drugs increasing hyperosmolarity such as polyethylene glycol causes neoangiogenesis and drusen-like structures in rodents. The link between AMD and hyperosmolarity is reinforced by the fact that treatments aiming to restore mitochondrial activity, such as lipoic acid and/or methylene blue, have been experimentally shown to be effective. We suggest that metabolic shift, inflammation, and hyperosmolarity are hallmarks in the pathogenesis and treatment of AMD. [ABSTRACT FROM AUTHOR]

Adapting the mechanical strength between the implant materials and the brain tissue is crucial for the postoperative treatment of glioblastoma. However, no related study has been reported. Herein, we report an injectable lipoic acid‑iron (LA-Fe) hydrogel (LFH) that can adapt to the mechanical strength of various brain tissues, including human brain tissue, by coordinating Fe3+ into a hybrid hydrogel of LA and its sodium salt (LANa). When LFH, which matches the mechanical properties of mouse brain tissue (337 ± 8.06 Pa), was injected into the brain resection cavity, the water content of the brain tissue was maintained at a normal level (77%). Similarly, LFH did not induce the activation or hypertrophy of glial astrocytes, effectively preventing brain edema and scar hyperplasia. Notably, LFH spontaneously degrades in the interstitial fluid, releasing LA and Fe3+ into tumor cells. The redox couples LA/DHLA (dihydrolipoic acid, reduction form of LA in cells) and Fe3+/Fe2+ would regenerate each other to continuously provide ROS to induce ferroptosis and activate immunogenic cell death. As loaded the anti-PDL1, anti-PDL1@LFH further enhanced the efficacy of tumor-immunotherapy and promoted tumor ferroptosis. The injectable hydrogel that adapted the mechanical strength of tissues shed a new light for the tumor postoperative treatment. TOC Graph: The first injectable hydrogel that can adapt the mechanical strength of different brain tissues including human brain has been developed for the GBM postoperative treatment without the involvement of anti-tumor drugs by coordinating Fe3+ into the hybrid hydrogel of B vitamin lipoic acid (LA) and its sodium salt (LANa). [Display omitted] • By coordinating Fe3+ into the hybrid hydrogel of lipoic acid (LA) and its sodium salt (LANa) formed an injectable hydrogel. • The LA-Fe hydrogel (LFH) can adapt the mechanical strength of multiple brain tissues including human brain. • The LFH circumvented the foreign body reaction caused by material implantation, and effectively inhibited tumor recurrence. • As loaded the anti-PDL1, anti-PDL1@LFH further enhanced the tumor-immunotherapy efficacy and promoted the tumor ferroptosis. [ABSTRACT FROM AUTHOR]

This study aims to evaluate the effects of adding alpha lipoic acid (ALA) to the in vitro ovarian tissue culture medium, either fresh or after vitrification/warming. For this purpose, 10 ovaries from five adult sheep were used. Each pair of ovaries gave rise to 16 fragments and were randomly distributed into two groups: fresh (n = 8) and vitrified (n = 8). Two fresh fragments were fixed immediately and considered the control, while another six were cultured in vitro for 14 days in the absence; presence of a constant (100 μM/0–14 day) or dynamic (50 μM/day 0–7 and 100 μM/day 8–14) concentration of ALA. As for the vitrified fragments, two were fixed and the other six were cultured in vitro under the same conditions described for the fresh group. All the fragments were subjected to morphological evaluation, follicular development and stromal density (classical histology), DNA fragmentation (TUNEL), senescence (Sudan Black), fibrosis (Masson's Trichome), and endoplasmic reticulum stress (immunofluorescence). Measurements of the antioxidant capacity against the free radicals 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 2,2-diphenyl-1-picryl-hydrazyl-hydrate (DPPH) and estradiol (E 2) levels in the culture medium was performed. The results showed that in the absence of ALA, in vitro culture of vitrified ovarian fragments showed a significant reduction (P < 0.05) in follicular morphology and increased the presence of senescence and tissue fibrosis (P < 0.05). Dynamic ALA maintained E 2 levels unchanged (P > 0.05) until the end of vitrified ovarian tissue culture and controlled the levels of ABTS and DPPH radicals in fresh or vitrified cultures. Therefore, it is concluded that ALA should be added to the vitrified ovarian tissue in vitro culture medium to reduce the damage that leads to loss of ovarian function. To ensure steroidogenesis during in vitro culture, ALA should be added dynamically (different concentrations throughout culture). • Addition of ALA to vitrified ovary in vitro culture medium reduces fibrosis and cellular senescence. • In vitro culture of vitrified ovary to restore endocrine function. • Conservation of ovarian follicles in situ. [ABSTRACT FROM AUTHOR]

Objective is to examine the background of IAS and the variations in drugs that trigger it among patients who have been genetically tested, aiming to deepen our understanding of this condition. HLA Analysis of 68 cases showed that DR4 is predominant, especially in individuals of East Asian descent, notably in DRB1 *0406. Methimazole was the primary drug associated with IAS in these populations, while in Caucasian individuals, the emphasis was on DRB1 *0403, with lipoic acid being the common inducer. The key factor determining disease risk is the combination of chromosomal allele variations, with HLA class II allele DR4 positive patients showing a strong association with DQA1 *0301/DQB1 *0302. [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]

This document explores the use of antioxidant nanoparticles in fields such as pharmaceutics, cosmetics, and food. The research articles and reviews included in the document discuss recent advancements in the design, production, characterization, and application of these nanoparticles. The papers cover various delivery systems, including nanoparticles, nanocomposites, and vesicles, and explore their potential uses in biomedical, pharmaceutical, cosmetic, and food industries. The article emphasizes the potential of antioxidant nanosystems in enhancing the effectiveness of treatments for diseases related to oxidative stress and calls for further research in this area. The authors also provide a list of contributions from other researchers in the field. [Extracted from the article]

Significant advancements have been achieved in polymer nanogel synthesis, yet there is a dearth of methods for easily preparing size‐adjustable, surface‐modifiable, and biocompatible nanogels. This study introduces a straightforward method for fabricating hyperbranched polyglycerol (HPG) nanogels in water through self‐assembly and disulfide bond crosslinking, avoiding the use of surfactants. The process involves modifying HPG with thioctic acid (TA) to create amphiphilic HPG‐TA rich in disulfide bonds, which is then reduced to facilitate water introduction and self‐assembly. Photocrosslinking is used to finalize the formation of HPG nanogels. These nanogels feature a uniform size distribution, with hydrodynamic diameters tunable from around 90 to 400 nm by tweaking synthesis variables. They have shown low cytotoxicity and high stability in aqueous media, with notable sensitivity to pH, especially in acidic conditions (e.g., pH 3), and redox‐responsiveness, as evidenced by reactions to 10 mM dithiothreitol (DTT). The nanogels' multiple hydroxyl groups enable easy functionalization, exemplified by the synthesis of fluorescent HPG‐RB nanogels. This work presents an efficient strategy for producing robust HPG nanogels, potentially spurring further advancements in the field of polymer nanogel synthesis and application. [ABSTRACT FROM AUTHOR]

Sulfur (S) is an essential element for life on Earth. Plants are able to take up and utilize sulfate (SO42–), the most oxidized inorganic form of S compounds on Earth, through the reductive S assimilatory pathway that couples with photosynthetic energy conversion. Organic S compounds are subsequently synthesized in plants and made accessible to animals, primarily as the amino acid methionine. Thus, plant S metabolism clearly has nutritional importance in the global food chain. S metabolites may be part of redox regulation and drivers of essential metabolic pathways as cofactors and prosthetic groups, such as Fe–S centers, CoA, thiamine, and lipoic acid. The evolution of the S metabolic pathways and enzymes reflects the critical importance of functional innovation and diversifications. Here we review the major evolutionary alterations that took place in S metabolism across different scales and outline research directions that may take advantage of understanding the evolutionary adaptations. [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]

Background: Ovarian granulosa cells (GCs) are essential for follicular development. Ovarian advanced glycation endproducts (AGEs) accumulation is related to GCs dysfunction. Alpha-lipoic acid (ALA) illustrates therapeutic capabilities for infertility-related disorders. Therefore, this study assessed the effects of ALA on AGEs-induced GCs hormonal dysfunction. Methods: The study was conducted from October 2021 to September 2022 at the Department of Medical Genetics, Shiraz University of Medical Sciences. Isolated GCs (n=50) were divided into control, human glycated albumin (HGA), HGA+ALA, and ALA treatments. Steroidogenic enzymes and AGE receptor (RAGE) genes were assessed by qRT-PCR. Steroid hormones and RAGE protein were evaluated using ELISA and Western blotting. Data were analyzed using GraphPad Prism software (ver. 9), and P<0.05 was considered significant. Results: Our findings showed that HGA treatment significantly (P=0.0001) increased RAGE (by 140.66%), STAR (by 117.65%), 3β-HSD (by 165.68%), and 17β-HSD (by 122.15%) expression, while it decreased CYP19A1 (by 68.37%) expression. RAGE protein level (by 267.10%) was also increased in HGA-treated GCs. A significant decrease in estradiol (by 59.66%) and a slight and sharp elevation in progesterone (by 30.40%) and total testosterone (by 158.24%) levels was also observed. ALA treatment ameliorated the HGA-induced changes in steroidogenic enzyme mRNA levels (P=0.001) and steroid hormone secretion (P=0.010). Conclusion: This work shows that ALA therapy likely corrects hormonal dysfunctions caused by AGEs in luteinized GCs. This effect is probably achieved by decreased RAGE expression. Clinical research is needed to understand how AGEs and ALA interact in the ovary, which might lead to a more targeted ovarian dysfunction therapy. [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]

Cancer cells are known to create an acidic microenvironment (the Warburg effect). At the same time, fluorescent dyes can be sensitive to pH, showing a sharp increase or decrease in fluorescence depending on pH. However, modern applications, such as confocal laser scanning microscopy (CLSM), set additional requirements for such fluorescent markers to be of practical use, namely, high quantum yield, low bleaching, minimal quenching in the cell environment, and minimal overlap with auto-fluorophores. R6G could be the perfect match for these requirements, but its fluorescence is not pH-dependent. We have attempted to develop an R6G conjugate with its FRET or PeT pair that would grant it pH sensitivity in the desired range (5.5–7.5) and enable the selective targeting of tumor cells, thus improving CLSM imaging. Covalent conjugation of R6G with NBD using a spermidine (spd) linker produced a pH-sensitive FRET effect but within the pH range of 7.0–9.0. Shifting this effect to the target pH range of 5.5–7.5 appeared possible by incorporating the R6G-spd-NBD conjugate within a "smart" polymeric micelle based on chitosan grafted with lipoic acid. In our previous studies, one could conclude that the polycationic properties of chitosan could make this pH shift possible. As a result, the micellar form of the NBD-spd-R6G fluorophore demonstrates a sharp ignition of fluorescence by 40%per1 pH unit in the pH range from 7.5 to 5. Additionally, "smart" polymeric micelles based on chitosan allow the label to selectively target tumor cells. Due to the pH sensitivity of the fluorophore NBD-spd-R6G and the selective targeting of cancer cells, the efficient visualization of A875 and K562 cells was achieved. CLSM imaging showed that the dye actively penetrates cancer cells (A875 and K562), while minimal accumulation and low fluorophore emission are observed in normal cells (HEK293T). It is noteworthy that by using "smart" polymeric micelles based on polyelectrolytes of different charges and structures, we create the possibility of regulating the pH dependence of the fluorescence in the desired interval, which means that these "smart" polymeric micelles can be applied to the visualization of a variety of cell types, organelles, and other structures. [ABSTRACT FROM AUTHOR]

Objective(s): Rhabdomyolysis, a potentially life-threatening condition, occurs when myoglobin is released from damaged muscle cells, leading to acute kidney injury (AKI). Alpha lipoic acid (ALA), an organosulfur compound known for its anti-oxidant and anti-inflammatory properties, was examined in this study for its potential impact on rhabdomyolysis-induced AKI in rats. Materials and Methods: Six groups of rats were included in the study, with each group consisting of six rats (n=6): Control, rhabdomyolysis, rhabdomyolysis treated with different doses of ALA (5, 10, and 20 mg/kg), and ALA alone (20 mg/kg) groups. Rhabdomyolysis was induced by intramuscular injection of glycerol on the first day of the experiment, while ALA was administered intraperitoneally for four consecutive days. Renal function parameters, oxidative stress markers, and histological changes in the kidneys were evaluated. Western blot analysis was performed to measure the levels of neutrophil gelatinase-associated lipocalin (NGAL) and tumor necrosis factor-alpha (TNF-α) proteins. Results: A significant increase in serum urea, creatinine, renal malondialdehyde, NGAl, and TNF-a protein levels was observed in glycerol-injected rats. In addition, a significant decrease in glutathione was recorded. Compared to the rhabdomyolysis group, treatment with ALA recovered kidney histological and biochemical abnormalities. Conclusion: Results suggest that rhabdomyolysis-induced AKI is associated with increased oxidative stress and inflammation. Treatment with ALA improved kidney histological abnormalities and reduced oxidative stress markers in rats. Therefore, ALA may have a potential protective effect against rhabdomyolysis-induced AKI. [ABSTRACT FROM AUTHOR]

Aims: In addition to reducing the respiratory function, crystalline silica (SiO2) disturbs the immune response by affecting immune cells during the progression of silicosis. Regulatory T cell (Treg) differentiation may play a key role in the abnormal polarization of T helper cell (Th)1 and Th2 cells in the development of silicosis-induced fibrosis. Alpha-lipoic acid (ALA) has immunomodulatory effects by promoting Tregs differentiation. Thus, ALA may have a therapeutic potential for treating autoimmune disorders in patients with silicosis. However, little is known regarding whether ALA regulates the immune system during silicosis development. Results: We found that the expression levels of collagen increased, and the antioxidant capacity was lower in the Lias−/−+SiO2 group than in the Lias+/++SiO2 group. The proportion of Tregs decreased in the peripheral blood and spleen tissue in mice exposed to SiO2. The proportion of Tregs in the Lias−/−+SiO2 group was significantly lower than that in the Lias+/++SiO2 group. Supplementary exogenous ALA attenuates the accumulation of inflammatory cells and extracellular matrix in lung tissues. ALA promotes the immunological balance between Th17 and Treg responses during the development of silicosis-induced fibrosis. Innovation and Conclusion: Our findings confirmed that low expression of lipoic acid synthase aggravates SiO2-induced silicosis, and that supplementary exogenous ALA has therapeutic potential by improving Tregs in silicosis fibrosis. [ABSTRACT FROM AUTHOR]

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. [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]

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. [ABSTRACT FROM AUTHOR]

This study aims to investigate the thermohydraulic performance of silver nanofluids with different surface modifications (citrate, lipoic acid, and silica) in turbulent convective heat transfer applications. Three silver nanofluids were prepared, each modified with citrate, lipoic acid, or silica coatings. The nanofluids were characterized for stability using zeta potential measurements and evaluated in a smooth brass tube under turbulent flow conditions. The experimental setup involved measuring the temperature, pressure, and flow rate to assess heat transfer coefficients, pressure drops, and friction factors. The results were compared with distilled water as the base fluid and validated against theoretical models. The silica-shelled nanofluid (Ag/S) exhibited a significant 35% increase in the average heat transfer coefficient compared to distilled water, while the citrate-coated (Ag/C) and lipoic acid-coated (Ag/L) nanofluids showed slight decreases of approximately 0.2% and 2%, respectively. The Ag/S nanofluid demonstrated a 9% increase in the mean Nusselt number, indicating enhanced heat transfer capabilities. However, all modified nanofluids experienced higher pressure drops and friction factors than the base fluid, with the Ag/S nanofluid showing the highest increase in viscosity (11.9%). Surface modifications significantly influence the thermohydraulic performance of silver nanofluids. The silica-shelled nanofluid shows the most substantial enhancement in heat transfer, making it a promising candidate for applications requiring efficient thermal management. However, the increased hydraulic costs associated with higher-pressure drops and friction factors must be carefully managed. Further research is needed to optimize these nanofluids for specific industrial applications, considering long-term stability and the effects of different nanoparticle concentrations and geometries. [ABSTRACT FROM AUTHOR]

α-Lipoic acid (LA) is an antioxidant of endogenous production, also obtained exogenously. Oxidative stress is closely associated with hypertension, which causes kidney injury and endothelial dysfunction. Here, we evaluated the cardiovascular and renal effects of LA in the two-kidney-one-clip (2K1C) hypertension model. The rats were divided into four groups: Sham surgery (Sham), the two-kidneys-one-clip (2K1C) group, and groups treated with LA for 14 days (Sham-LA and 2K1C-LA). No changes were observed in the pattern of food, water intake, and urinary volume. The left/right kidney weight LKw/RKw ratio was significantly higher in 2K1C animals. LA treatment did not reverse the increase in cardiac mass. In relation to vascular reactivity, there was an increase in the potency of phenylephrine (PHE) curve in the hypertensive animals treated with LA compared to the 2K1C group and also compared to the Sham group. Vasorelaxation induced by acetylcholine (Ach) and sodium nitroprusside (SNP) were not improved by treatment with LA. Urea and creatinine levels were not altered by the LA treatment. In conclusion, the morphological changes in the aorta and heart were not reversed; however, the treatment with LA mitigated the contraction increase induced by the 2K1C hypertension. [ABSTRACT FROM AUTHOR]

Alpha-lipoic acid (ALA) is a naturally occurring compound synthesized by mitochondria and widely distributed in both animal and plant tissues. It primarily influences cellular metabolism and oxidative stress networks through its antioxidant properties and is an important drug for treating metabolic diseases associated with oxidative damage. Nevertheless, research indicates that the mechanism by which ALA affects cancer cells is distinct from that observed in normal cells, exhibiting pro-oxidative properties. Therefore, this review aims to describe the main chemical and biological functions of ALA in the cancer environment, including its mechanisms and effects in tumor prevention and anticancer activity, as well as its role as an adjunctive drug in cancer therapy. We specifically focus on the interactions between ALA and various carcinogenic and anti-carcinogenic pathways and discuss ALA's pro-oxidative capabilities in the unique redox environment of cancer cells. Additionally, we elaborate on ALA's roles in nanomedicine, hypoxia-inducible factors, and cancer stem cell research, proposing hypotheses and potential explanations for currently unresolved issues. [ABSTRACT FROM AUTHOR]

Abstract 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.

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. [ABSTRACT FROM AUTHOR]

Copper is an important metal micronutrient, required for the balanced growth and normal physiological functions of human organism. Copper-related toxicity and dysbalanced metabolism were associated with the disruption of intracellular respiration and the development of various diseases, including cancer. Notably, copper-induced cell death was defined as cuproptosis which was also observed in malignant cells, representing an attractive anti-cancer instrument. Excess of intracellular copper leads to the aggregation of lipoylation proteins and toxic stress, ultimately resulting in the activation of cell death. Differential expression of cuproptosis-related genes was detected in normal and malignant tissues. Cuproptosis-related genes were also linked to the regulation of oxidative stress, immune cell responses, and composition of tumor microenvironment. Activation of cuproptosis was associated with increased expression of redox-metabolism-regulating genes, such as ferredoxin 1 (FDX1), lipoic acid synthetase (LIAS), lipoyltransferase 1 (LIPT1), dihydrolipoamide dehydrogenase (DLD), drolipoamide S-acetyltransferase (DLAT), pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1), and pyruvate dehydrogenase E1 subunit beta (PDHB)). Accordingly, copper-activated network was suggested as an attractive target in cancer therapy. Mechanisms of cuproptosis and regulation of cuproptosis-related genes in different cancers and tumor microenvironment are discussed in this study. The analysis of current findings indicates that therapeutic regulation of copper signaling, and activation of cuproptosis-related targets may provide an effective tool for the improvement of immunotherapy regimens. Key messages: Facts • Copper ions, essential components of human body, can activate a novel subtype of programmed cell death, defined as cuproptosis. • Cuproptosis is tightly associated with the regulation of mitochondrial respiration and oxidative stress in various cells, including malignant. • Changed concentration of copper ions was found to regulate a set of redox-metabolism-regulating genes, such as ferredoxin 1, lipoic acid synthetase, lipoyltransferase 1, dihydrolipoamide dehydrogenase, drolipoamide S-acetyltransferase, and pyruvate dehydrogenase E1 subunits alpha 1 and beta. • Cuproptosis-related genes and copper-containing compounds were indicated as potential targets and tools for the development of novel anti-cancer therapy. Open Questions • How to target cuproptosis-related genes to stop cancer cell survival? • Which copper-responsive targets and/or copper-containing compounds can be employed safely and effectively during cancer treatment? • Which biomarkers can be reliably employed to define good response to the activation of cuproptosis in cancer cells? • Are there others, undiscovered intracellular targets of copper which can be used for cancer prevention and treatment? [ABSTRACT FROM AUTHOR]

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-β 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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [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]

Liquid-filled hard gelatin capsules may have pertinent advantages both for therapeutic effect and extemporaneous preparations of medicines. Alpha lipoic acid is a substance used in medicines and dietary supplements and there is a need for creating an appropriate formulation which would be suitable for each individual patient or consumer. Based on its biopharmaceutical and physical chemical characteristics, eight different capsule formulations were designed and characterized. Silicon dioxide was added to form a semisolid content and prevent leakage. The formulation filled with alpha lipoic acid solution in polyethylene glycol 400 showed the best performance. Although the addition of silicon dioxide to the formulation with polyethylene glycol 400 led to a change in both flow character and viscosity, the release rate did not show a statistically significant decrease (more than 85% of content was released after 5 min testing). Applied technique is a simple and an appropriate approach for compounding and could be used for other substances with similar properties. [ABSTRACT FROM AUTHOR]

Purpose: To investigate the effect of lipoic acid combination with valsartan on diabetic nephropathy (DN) and its associated adverse reactions. Methods: A retrospective analysis was conducted on 120 patients who treated for DN at the Second Affiliated Hospital of Shenzhen University, China between August 2019 and October 2022. Based on different treatment approaches, control group comprised 55 patients receiving valsartan alone, while joint group consisted of 65 patients receiving a combination of valsartan and lipoic acid. Therapeutic effectiveness and adverse events were compared between the groups. Additionally, changes in blood glucose and renal function parameters were evaluated pre- and post-treatment. Results: Post-treatment, both groups exhibited improvements in blood glucose and renal function parameters compared to pre-treatment values (p < 0.05). However, joint group demonstrated superior improvements in these parameters compared to control group (p < 0.05). Total efficacy was significantly higher in the joint group than in control group (p < 0.05). No significant differences were observed between the groups' incidence of adverse reactions (p > 0.05). Conclusion: Concurrent therapy of lipoic acid and valsartan sly treats DN. It enhances the regulation of blood glucose levels and improves renal function with high safety. Further studies employing larger sample sizes and prospective designs with comprehensive patient follow-up are required to further validate and enhance the reliability of these findings. [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]

The pursuit of enhanced health during aging has prompted the exploration of various strategies focused on reducing the decline associated with the aging process. A key area of this exploration is the management of mitochondrial dysfunction, a notable characteristic of aging. This review sheds light on the crucial role that small molecules play in augmenting healthy aging, particularly through influencing mitochondrial functions. Mitochondrial oxidative damage, a significant aspect of aging, can potentially be lessened through interventions such as coenzyme Q10, alpha‐lipoic acid, and a variety of antioxidants. Additionally, this review discusses approaches for enhancing mitochondrial proteostasis, emphasizing the importance of mitochondrial unfolded protein response inducers like doxycycline, and agents that affect mitophagy, such as urolithin A, spermidine, trehalose, and taurine, which are vital for sustaining protein quality control. Of equal importance are methods for modulating mitochondrial energy production, which involve nicotinamide adenine dinucleotide boosters, adenosine 5′‐monophosphate‐activated protein kinase activators, and compounds like metformin and mitochondria‐targeted tamoxifen that enhance metabolic function. Furthermore, the review delves into emerging strategies that encourage mitochondrial biogenesis. Together, these interventions present a promising avenue for addressing age‐related mitochondrial degradation, thereby setting the stage for the development of innovative treatment approaches to meet this extensive challenge. [ABSTRACT FROM AUTHOR]

Infrared transmitting materials (IRTMs) are prone to mechanical and corrosion damage during long‐time exposure to harsh outside environments. However, conventional IRTMs frequently lack self‐repairability that limit their lifespan. To address the limitation, thioctic acid‐based epoxy resins (TAEs) are developed from natural thioctic acid and commercial epoxy monomers. The double ring‐opening polymerization (ROP) reactions of thioctic acid and epoxy groups result in dual dynamic covalent bonds with varying bond energies containing relatively weak disulfide bonds and strong ester bonds. As compared with conventional covalent adaptable networks (CANs) that present rapid creep properties when heated, TAEs maintain their geometric stability during rapid self‐repairing at a mild temperature of 80 °C by enhancing network integrity through stable ester crosslinking points. The feature renders TAEs self‐repairing capability while maintaining precise geometrical dimensions, which is suitable for infrared transmitting devices. On the other hand, TAEs exhibit high near‐infrared transmittance (>80%). Therefore, TAEs with self‐repairability and high infrared transmittance demonstrate they can be used as superior polymeric IRTM. [ABSTRACT FROM AUTHOR]

This study introduces newly discovered chrysin derivatives that show potential as candidate molecules for treating inflammatory bowel disease (IBD). Compound 4b, among the synthesized compounds, displayed significant inhibitory effects on monocyte adhesion to colon epithelium induced by TNF-α, with an IC50 value of 4.71 μM. Furthermechanistic studies demonstrated that 4b inhibits the production of reactive oxygen species (ROS) and downregulates the expression of ICAM-1 and MCP-1, key molecules involved in monocyte-epithelial adhesion, as well as the transcriptional activity of NF-κB. In vivo experiments have shown that compound 4b exhibits a dose-dependent inhibition of 2, 4, 6-trinitrobenzenesulfonic acid (TNBS)- induced colitis in rats, thereby validating its effectiveness as a colitis inhibitor in animal models. These results indicate that 4b shows considerable promise as a therapeutic agent for managing IBD. [ABSTRACT FROM AUTHOR]

Objective: The purpose of this experimental research is to investigate the effects of High-Intensity Interval Training (HIIT) and Lipoic Acid)ALA(supplementation on VEGFR-3 of pancreatic in diabetic Wistar rats model. Materials and Methods: 20 male Wistar rats weighing 159 ± 3 gr and aged3 weeks, were randomly assigned into 4 groups:1) diabetes/sham, 2)diabetes/ALA, 3)diabetes/exercise/sham, and 4) diabetes/exercise/ALA. Diabetes was induced with streptozotocin (65 mg/kg dose) and Nicotinamide (120 mg/kg dose). After two weeks of familiarization with interval training, the rats started their main training, included 10 repetitions of 4 minutes of running on the treadmill with an intensity of 85-90% VO2max and 2 minutes of active rest between repetitions (5-10 m/min) for 5 sessions per week for 6 weeks. ALA supplement was taken at a dose of 20 mg/kg/day for 6 weeks. One-way ANOVA test used and Tukey's post hoc test at for analysis (P= 0.05). Results: HIIT has a significant effect on blood glucose (P= 0.004) and insulin (P= 0.001) and VEGFR3 (P= 0.001) of pancreatic tissue of diabetic rats. Conclusion: Lymphatic vessels play an important role in the pancreas and treat diabetes. The results of this research showed that HIIT and ALA increased lymphangiogenesis in the diabetic rat model. [ABSTRACT FROM AUTHOR]

Lipoic acid trisulfide, a sulfane sulfur-containing trisulfide of α-lipoic acid, holds promise in pharmaceuticals, yet knowledge gaps persist regarding its synthesis, properties, and stability. Here, we synthesized the lipoic acid trisulfide with a purity exceeding 99% from α -lipoic acid on a gram scale and obtained novel β - cyclodextrin clathrates (84%-95% yield). Differential scanning calorimetry confirmed the inclusion of lipoic acid trisulfide in β-cyclodextrins. The resulting β-cyclodextrin clathrates exhibited significant improvements in water solubility and thermal stability. This pioneering study demonstrated a novel approach to the practical preparation of trisulfide and its β-cyclodextrin clathrates as active ingredients, paving the way for clinical development. [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]

Having evolved from a prokaryotic origin, mitochondria retain pathways required for the catabolism of energy‐rich molecules and for the biosynthesis of molecules that aid catabolism and/or participate in other cellular processes essential for life of the cell. Reviewed here are details of the mitochondrial fatty acid biosynthetic pathway (FAS II) and its role in building both the octanoic acid precursor for lipoic acid biosynthesis (LAS) and longer‐chain fatty acids functioning in chaperoning the assembly of mitochondrial multisubunit complexes. Also covered are the details of mitochondrial lipoic acid biosynthesis, which is distinct from that of prokaryotes, and the attachment of lipoic acid to subunits of pyruvate dehydrogenase, α‐ketoglutarate dehydrogenase, and glycine cleavage system complexes. Special emphasis has been placed on presenting what is currently known about the interconnected paths and loops linking the FAS II–LAS pathway and two other mitochondrial realms, the organellar translation machinery and Fe‐S cluster biosynthesis and function. [ABSTRACT FROM AUTHOR]

Background: AMP-activated protein kinase (AMPK) is a key enzyme for cellular energy homeostasis and improves metabolic disorders. Brown and beige adipose tissues exert thermogenesis capacities to dissipate energy in the form of heat. Here, we investigated the beneficial effects of the antioxidant alpha-lipoic acid (ALA) in menopausal obesity and the underlying mechanisms. Methods: Female Wistar rats (8 weeks old) were subjected to bilateral ovariectomy (Ovx) and divided into four groups: Sham (n=8), Ovx (n=11), Ovx+ALA2 (n=10), and Ovx+ALA3 (n=6) (ALA 200 and 300 mg/kg/day, respectively; gavage) for 8 weeks. 3T3-L1 cells were used for in vitro study. Results: Rats receiving ALA2 and ALA3 treatment showed significantly lower levels of body weight and white adipose tissue (WAT) mass than those of the Ovx group. ALA improved plasma lipid profiles including triglycerides, total cholesterol, low-density lipoprotein cholesterol, and high-density lipoprotein cholesterol. Hematoxylin & eosin staining of inguinal WAT showed that ALA treatment reduced Ovx-induced adipocyte size and enhanced uncoupling protein 1 (UCP1) expression. Moreover, plasma levels of irisin were markedly increased in ALA-treated Ovx rats. Protein expression of brown fat-specific markers including UCP1, PRDM16, and CIDEA was downregulated by Ovx but markedly increased by ALA. Phosphorylation of AMPK, its downstream acetyl-CoA carboxylase, and its upstream LKB1 were all significantly increased by ALA treatment. In 3T3-L1 cells, administration of ALA (100 and 250 μM) reduced lipid accumulation and enhanced oxygen consumption and UCP1 protein expression, while inhibition of AMPK by dorsomorphin (5 μM) significantly reversed these effects. Conclusion: ALA improves estrogen deficiency-induced obesity via browning of WAT through AMPK signaling. [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]

Endogenous formaldehyde (FA) is produced in the human body via various mechanisms to preserve healthy energy metabolism and safeguard the organism. However, endogenous FA can have several negative effects on the body through epigenetic alterations, including cancer growth promotion; neuronal, hippocampal and endothelial damages; atherosclerosis acceleration; haemopoietic stem cell destruction and haemopoietic cell production reduction. Certain medications with antioxidant effects, such as glutathione, vitamin E, resveratrol, alpha lipoic acid and polyphenols, lessen the detrimental effects of endogenous FA by reducing oxidative stress, directly scavenging endogenous FA or promoting its degradation. This study offers fresh perspectives for managing illnesses associated with endogenous FA exposure. This article reviews the physiological and pathological mechanisms underlying the production and metabolism of endogenous formaldehyde, as well as its bidirectional regulatory effects on the human body. Finally, drugs that eliminate endogenous formaldehyde are summarized. This review provides a new perspective on how to treat diseases caused by endogenous formaldehyde in the future. [ABSTRACT FROM AUTHOR]

Chronic hypertension is a major risk factor for preeclampsia (PE), associated with significant maternal and neonatal morbidity. We previously demonstrated that pregnant stroke-prone spontaneously hypertensive rats (SHRSP) display a spontaneous PE-like phenotype with distinct placental, fetal, and maternal features. Here, we hypothesized that supplementation with alpha lipoic acid (ALA), a potent antioxidant, during early pregnancy could ameliorate the PE phenotype in this model. To test this hypothesis, timed pregnancies were established using 10 to 12-week-old SHRSP females (n = 19–16/group), which were assigned to two treatment groups: ALA (injected intraperitoneally with 25 mg/kg body weight ALA on gestation day (GD1, GD8, and GD12) or control, receiving saline following the same protocol. Our analysis of maternal signs showed that ALA prevented the pregnancy-dependent maternal blood pressure rise (GD14 blood pressure control 169.3 ± 19.4 mmHg vs. 146.1 ± 13.4 mmHg, p = 0.0001) and ameliorated renal function, as noted by the increased creatinine clearance and improved glomerular histology in treated dams. Treatment also improved the fetal growth restriction (FGR) phenotype, leading to increased fetal weights (ALA 2.19 ± 0.5 g vs. control 1.98 ± 0.3 g, p = 0.0074) and decreased cephalization indexes, indicating a more symmetric fetal growth pattern. This was associated with improved placental efficiency, decreased oxidative stress marker expression on GD14, and serum soluble fms-like tyrosine kinase 1 (sFlt1) levels on GD20. In conclusion, ALA supplementation mitigated maternal signs and improved placental function and fetal growth in SHRSP pregnancies, emerging as a promising therapy in pregnancies at high risk for PE. [ABSTRACT FROM AUTHOR]

Bacterial infections have a serious impact on public health. It is urgent to develop antibacterial hydrogels with good biocompatibility to reduce the use of antibiotics. In this study, poly(lipoic acid-co-sodium lipoate)–phytic acid (P(LA-SL)-PA) hydrogels are prepared by a simple mixture of the natural small molecules lipoic acid (LA) and phytic acid (PA) in a mild and green reaction environment. The crosslinking network is constructed through the connection of covalent disulfide bonds as well as the hydrogen bonds, which endow the injectable and self-healing properties. The P(LA-SL)-PA hydrogels exhibit an adjustable compression modulus and adhesion. The in vitro agar plates assay indicates that the antibacterial rate of hydrogels against Escherichia coli and Staphylococcus aureus is close to 95%. In the rat-infected wound model, the P(LA-SL)-PA hydrogels adhere closely to the tissue and promote epithelialization and collagen deposition with a significant effect on wound healing. These results prove that the P(LA-SL)-PA hydrogels could act as effective wound dressings for promoting the healing of infected wounds. [ABSTRACT FROM AUTHOR]