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

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

Nephro-protective effects of alpha-lipoic acid in type I diabetes.

Type 1 diabetes (T1D) is an insulin-dependent autoimmune condition. Short chain fatty acids (SCFAs) are volatile fatty acids with 1-6 carbon atoms that influence glucose storage in the body and can reduce appetite, potentially decreasing T1D risk. Alpha-lipoic acid (α-LA), a type of SCFA, has previously been used to treat diabetic neuropathy and inflammation due to its antioxidant properties. This study aims to assess α-LA's protective effects against T1D and associated kidney damage in rats induced with streptozotocin. Diabetic rats were treated with α-LA orally for 15 days, resulting in improved blood glucose (56% decrease) and kidney function markers like blood urea nitrogen, creatinine and uric acid. α-LA also showed significant antioxidant effects by decreasing LPO as well as improving activities of antioxidant enzymes like superoxide dismutase, catalase and glutathione-S transferase and alleviated kidney damage caused by diabetes. Docking experiments suggest that α-LA may regulate diabetes-related changes at the epigenetic level through interactions with the SIRT1 protein, indicating its potential as a target for future antidiabetic drug development.

Alpha lipoic acid administration improved both peripheral sensitivity to insulin and liver clearance of insulin reducing potential risk of diabetes and nonalcoholic fatty liver disease in overweight/obese PCOS patients.

OBJECTIVE: To evaluate the effects of alpha lipoic acid (ALA) on hormonal and metabolic parameters in a group of overweight/obese Polycystic Ovary Syndrome (PCOS) patients. METHODS: This was a retrospective study in which thirty-two overweight/obese patients with PCOS (n = 32) not requiring hormonal treatment were selected from the database of the ambulatory clinic of the Gynecological Endocrinology Center at the University of Modena and Reggio Emilia, Italy. The hormonal profile, routine exams and insulin and C-peptide response to oral glucose tolerance test (OGTT) were evaluated before and after 12 weeks of complementary treatment with ALA (400 mg/day). Hepatic Insulin Extraction (HIE) index was also calculated. RESULTS: ALA administration significantly improved insulin sensitivity and decreased ALT and AST plasma levels in all subjects, though no changes were observed on reproductive hormones. When PCOS patients were subdivided according to the presence or absence of familial diabetes background, the higher effects of ALA were observed in the former group that showed AST and ALT reduction and greater HIE index decrease. CONCLUSION: ALA administration improved insulin sensitivity in overweight/obese PCOS patients, especially in those with familial predisposition to diabetes. ALA administration improved both peripheral sensitivity to insulin and liver clearance of insulin. Such effects potentially decrease the risk of nonalcoholic fat liver disease and diabetes in PCOS patients.

Biological applications of lipoic acid-based polymers: an old material with new promise.

Lipoic acid (LA) is a versatile antioxidant that has been used in the treatment of various oxidation-reduction diseases over the past 70 years. Owing to its large five-membered ring tension, the dynamic disulfide bond of LA is highly active, enabling the formation of poly(lipoic acid) (PLA) via ring-opening polymerization (ROP). Herein, we first summarize disulfide-mediated ROP polymerization strategies, providing basic routes for designing and preparing PLA-based materials. PLA, as a biologically derived, low toxic, and easily modified material, possesses dynamic disulfide bonds and universal non-covalent carboxyl groups. We also shed light on the biomedical applications of PLA-based materials based on their biological and structural features and further divide recent works into six categories: antibacterial, anti-inflammation, anticancer, adhesive, flexible electronics, and 3D-printed tissue scaffolds. Finally, the challenges and future prospects associated with the biomedical applications of PLA are discussed.

Lipoic acid alters the microRNA signature in breast cancer cells.

BACKGROUND: Breast cancer, the deadliest disease affecting women globally, exhibits heterogeneity with distinct molecular subtypes. Despite advances in cancer therapy, the persistence of high mortality rates due to chemotherapy resistance remains a major challenge. Lipoic acid (LA), a natural antioxidant, has proven potent anticancer properties. Yet, the impact of LA on microRNA (miRNA) expression profile in breast cancer remains unexplored. AIM: The aim of this study was to unravel the effect of LA on miRNA expression profiles in different breast cancer cell lines. METHODS: The MiRCURY LNA miRNA miRNome qPCR Panel was used to compare the miRNA signature in MDA-MB-231 and MCF-7 cells treated or not with LA. RESULTS: We identified six upregulated and six downregulated miRNAs in LA-treated MDA-MB-231 cells and 14 upregulated and four downregulated miRNAs in LA-treated MCF-7 cells compared to control cells. KEGG (Kyoto Encyclopedia of Genes and Genomes) pathway analysis revealed that the deregulated miRNAs could alter different signaling cascades including FoxO, P53 and Hippo pathways. CONCLUSION: The outcome of this study provides further insights into the molecular mechanisms underlying the therapeutic benefit of LA. This in turn could assist the amelioration of LA-based anticancer therapies.

Solubilization and stabilization of lipoic acid trisulfide by creation of various ß-cyclodextrin clathrates.

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 ß-cyclodextrin clathrates (84%-95% yield). Differential scanning calorimetry confirmed the inclusion of lipoic acid trisulfide in ß-cyclodextrins. The resulting ß-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 ß-cyclodextrin clathrates as active ingredients, paving the way for clinical development.

Discovery of neuroprotective Agents: Potent, brain Penetrating, lipoic acid derivatives for the potential treatment of ischemic stroke by regulating oxidative stress and inflammation - a Preliminary study.

Stroke poses a serious risk to the physical and mental health of patients. Endogenous compounds are widely used to treat ischemic stroke. Lipoic acid, a naturally occurring (R)-5-(1,2-dithiolan-3-yl)pentanoic acid, has therapeutic potential for the treatment of ischemic stroke. However, the direct application of lipoic acid is limited by its relatively low efficacy and instability. Therefore, there is a need to modify the structure of lipoic acid to improve its pharmaceutical capabilities. Currently, 37 lipoic acid derivatives have been synthesized, and compound AA-9 demonstrated optimal therapeutic potential in an in vitro model of induced oxidative damage using tert-butyl hydroperoxide (t-BHP). In addition, in vitro experiments have shown that compound AA-9 has an excellent safety profile. Subsequently, the therapeutic effect of AA-9 was significant in the rat MCAO ischemic stroke model, which may be attributed to the antioxidant and anti-inflammatory effects of compound AA-9 by activating PGC-1α and inhibiting NLRP3. Notably, compound AA-9 exhibited higher stability and better bioavailability properties than ALA in plasma stability and pharmacokinetic properties. In conclusion, AA-9 may be a promising neuroprotective agent for the treatment of ischemic stroke and warrants further investigation.

Anti-cancer effects of alpha lipoic acid, cisplatin and paclitaxel combination in the OVCAR-3 ovarian adenocarcinoma cell line.

BACKGROUND: Ovarian cancer is the leading cause of gynecological cancer deaths. One of the major challenges in treating ovarian cancer with chemotherapy is managing the resistance developed by cancer cells to drugs, while also minimizing the side effects caused by these agents In the present study, we aimed to examine the effects of a combination of alpha lipoic acid (ALA), with cisplatin and paclitaxel in ovarian cancer(OVCAR-3). METHODS: The cytotoxic effects of ALA, cisplatin and paclitaxel on OVCAR-3 cells were determined. Four groups were formed: Control, ALA, Cisplatin + Paclitaxel, ALA + Cisplatin + Paclitaxel. The effects of single and combined therapy on cell migration, invasion and colony formation were analyzed. Changes in the expression of genes related to apoptosis, cell adhesion and cell cycle were analyzed with Real-time polymerase chain reaction(RT-PCR). The oxidative stress index and The Annexin V test were performed. RESULTS: The reduction in rapamycin-insensitive companion of mTOR(RICTOR) expression in the ALA + Cisplatin + Paclitaxel group was found statistically significant(p < 0.05). The decrease in MMP-9 and - 11 expressions the ALA + Cisplatin + Paclitaxel group was statistically significant(p < 0.05). The lowest values for mitogen-activated protein kinase(MAPK) proteins were found in the ALA + Cisplatin + Paclitaxel group. No colony formation was observed in the Cisplatin + Paclitaxel and ALA + Cisplatin + Paclitaxel groups. The lowest wound healing at 24 h was seen in the ALA + Cisplatin + Paclitaxel group. CONCLUSIONS: This study is the first one to investigate the combined treatment of ALA, Cisplatin, Paclitaxel on OVCAR-3. While ALA alone was not effective, combined therapy with ALA, has been found to reduce cell invasion, especially wound healing in the first 24 h, along with tumor cell adhesion.

Small-molecule α-lipoic acid targets ELK1 to balance human neutrophil and erythrocyte differentiation.

BACKGROUND: Erythroid and myeloid differentiation disorders are commonly occurred in leukemia. Given that the relationship between erythroid and myeloid lineages is still unclear. To find the co-regulators in erythroid and myeloid differentiation might help to find new target for therapy of myeloid leukemia. In hematopoiesis, ALA (alpha lipoic acid) is reported to inhibit neutrophil lineage determination by targeting transcription factor ELK1 in granulocyte-monocyte progenitors via splicing factor SF3B1. However, further exploration is needed to determine whether ELK1 is a common regulatory factor for erythroid and myeloid differentiation. METHODS: In vitro culture of isolated CD34+, CMPs (common myeloid progenitors) and CD34+ CD371- HSPCs (hematopoietic stem progenitor cells) were performed to assay the differentiation potential of monocytes, neutrophils, and erythrocytes. Overexpression lentivirus of long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 transduced CD34+ HSPCs were transplanted into NSG mice to assay the human lymphocyte and myeloid differentiation differences 3 months after transplantation. Knocking down of SRSF11, which was high expressed in CD371+GMPs (granulocyte-monocyte progenitors), upregulated by ALA and binding to ELK1-RNA splicing site, was performed to analyze the function in erythroid differentiation derived from CD34+ CD123mid CD38+ CD371- HPCs (hematopoietic progenitor cells). RNA sequencing of L-ELK1 and S-ELK1 overexpressed CD34+ CD123mid CD38+ CD371- HPCs were performed to assay the signals changed by ELK1. RESULTS: Here, we presented new evidence that ALA promoted erythroid differentiation by targeting the transcription factor ELK1 in CD34+ CD371- hematopoietic stem progenitor cells (HSPCs). Overexpression of either the long isoform (L-ELK1) or the short isoform (S-ELK1) of ELK1 inhibited erythroid-cell differentiation, but knockdown of ELK1 did not affect erythroid-cell differentiation. RNAseq analysis of CD34+ CD123mid CD38+ CD371- HPCs showed that L-ELK1 upregulated the expression of genes related to neutrophil activity, phosphorylation, and hypoxia signals, while S-ELK1 mainly regulated hypoxia-related signals. However, most of the genes that were upregulated by L-ELK1 were only moderately upregulated by S-ELK1, which might be due to a lack of serum response factor interaction and regulation domains in S-ELK1 compared to L-ELK1. In summary, the differentiation of neutrophils and erythrocytes might need to rely on the dose of L-ELK1 and S-ELK1 to achieve precise regulation via RNA splicing signals at early lineage commitment. CONCLUSIONS: ALA and ELK1 are found to regulate both human granulopoiesis and erythropoiesis via RNA spliceosome, and ALA-ELK1 signal might be the target of human leukemia therapy.

Ångstrom-scale gold particles loaded with alendronate via alpha-lipoic acid alleviate bone loss in osteoporotic mice.

Osteoporosis is a highly prevalent metabolic disease characterized by low systemic bone mass and deterioration of bone microarchitecture, resulting in reduced bone strength and increased fracture risk. Current treatment options for osteoporosis are limited by factors such as efficacy, cost, availability, side effects, and acceptability to patients. Gold nanoparticles show promise as an emerging osteoporosis therapy due to their osteogenic effects and ability to allow therapeutic delivery but have inherent constraints, such as low specificity and the potential for heavy metal accumulation in the body. This study reports the synthesis of ultrasmall gold particles almost reaching the Ångstrom (Ång) dimension. The antioxidant alpha-lipoic acid (LA) is used as a dispersant and stabilizer to coat Ångstrom-scale gold particles (AuÅPs). Alendronate (AL), an amino-bisphosphonate commonly used in drug therapy for osteoporosis, is conjugated through LA to the surface of AuÅPs, allowing targeted delivery to bone and enhancing antiresorptive therapeutic effects. In this study, alendronate-loaded Ångstrom-scale gold particles (AuÅPs-AL) were used for the first time to promote osteogenesis and alleviate bone loss through regulation of the WNT signaling pathway, as shown through in vitro tests. The in vivo therapeutic effects of AuÅPs-AL were demonstrated in an established osteoporosis mouse model. The results of Micro-computed Tomography, histology, and tartrate-resistant acid phosphatase staining indicated that AuÅPs-AL significantly improved bone density and prevented bone loss, with no evidence of nanoparticle-associated toxicity. These findings suggest the possible future application of AuÅPs-AL in osteoporosis therapy and point to the potential of developing new approaches for treating metabolic bone diseases using Ångstrom-scale gold particles.

Low-Triggering-Potential and Narrow-Potential-Window Electrochemiluminescence of Silver Nanoclusters for Gene Assay.

A low-triggering potential and a narrow-potential window are anticipated to decrease the electrochemical interference and cross talk of electrochemiluminescence (ECL). Herein, by exploiting the low oxidative potential (0.82 V vs Ag/AgCl) of dihydrolipoic acid-capped sliver nanoclusters (DHLA-AgNCs), a coreactant ECL system of DHLA-AgNCs/hydrazine (N2H4) is proposed to achieve efficient and oxidative-reduction ECL with a low-triggering potential of 0.82 V (vs Ag/AgCl) and a narrow-potential window of 0.22 V. The low-triggering-potential and narrow-potential-window nature of ECL can be primarily preserved upon labeling DHLA-AgNCs to probe DNA and immobilizing DHLA-AgNCs onto the Au surface via sandwiched hybridization, which eventually enables a selective ECL strategy for the gene assay at +0.82 V. This gene assay strategy can sensitively determine the gene of human papillomavirus from 10 to 1000 pM with a low limit of detection of 5 pM (S/N = 3) and would open a way to improve the applied ECL bioassay.

Lipoic acid-mediated oral drug delivery system utilizing changes on cell surface thiol expression for the treatment of diabetes and inflammatory diseases.

Lipoic acid (LA), which has good safety and oral absorption, is obtained from various plant-based food sources and needs to be supplemented through human diet. Moreover, substances with a disulfide structure can enter cells through dynamic covalent disulfide exchange with thiol groups on the cell membrane surface. Based on these factors, we constructed LA-modified nanoparticles (LA NPs). Our results showed that LA NPs can be internalized into intestinal epithelial cells through surface thiols, followed by intracellular transcytosis via the endoplasmic reticulum-Golgi pathway. Further mechanistic studies indicated that disulfide bonds within the structure of LA play a critical role in this transport process. In a type I diabetes rat model, the oral administration of insulin-loaded LA NPs exhibited a more potent hypoglycemic effect, with a pharmacokinetic bioavailability of 5.42 ± 0.53%, representing a 1.6 fold enhancement compared to unmodified PEG NPs. Furthermore, a significant upregulation of surface thiols in inflammatory macrophages was reported. Thus, we turned our direction to investigate the uptake behavior of inflammatory macrophages with increased surface thiols towards LA NPs. Inflammatory macrophages showed a 2.6 fold increased uptake of LA NPs compared to non-inflammatory macrophages. Surprisingly, we also discovered that the antioxidant resveratrol facilitates the uptake of LA NPs in a concentration-dependent manner. This is mainly attributed to an increase in glutathione, which is involved in thiol uptake. Consequently, we employed LA NPs loaded with resveratrol for the treatment of colitis and observed a significant alleviation of colitis symptoms. These results suggest that leveraging the variations of thiol expression levels on cell surfaces under both healthy and diseased states through an oral drug delivery system mediated by the small-molecule nutrient LA can be employed for the treatment of diabetes and certain inflammatory diseases.

Comparing the effects of developmental exposure to alpha lipoic acid (ALA) and perfluorooctanesulfonic acid (PFOS) in zebrafish (Danio rerio).

Alpha lipoic acid (ALA) is a dietary supplement that has been used to treat a wide range of diseases, including obesity and diabetes, and have lipid-lowering effects, making it a potential candidate for mitigating dyslipidemia resulting from exposures to the per- and polyfluoroalkyl substance (PFAS) family member perfluorooctanesulfonic acid (PFOS). ALA can be considered a non-fluorinated structural analog to PFOS due to their similar 8-carbon chain and amphipathic structure, but, unlike PFOS, is rapidly metabolized. PFOS has been shown to reduce pancreatic islet area and induce ß-cell lipotoxicity, indicating that changes in ß-cell lipid microenvironment is a mechanism contributing to hypomorphic islets. Due to structural similarities, we hypothesized that ALA may compete with PFOS for binding to proteins and distribution throughout the body to mitigate the effects of PFOS exposure. However, ALA alone reduced islet area and fish length, with several morphological endpoints indicating additive toxicity in the co-exposures. Individually, ALA and PFOS increased fatty acid uptake from the yolk. ALA alone increased liver lipid accumulation, altered fatty acid profiling and modulated PPARÉ£ pathway signaling. Together, this work demonstrates that ALA and PFOS have similar effects on lipid uptake and metabolism during embryonic development in zebrafish.

A silk-based hydrogel containing dexamethasone and lipoic acid microcrystals for local delivery to the inner ear.

Local drug delivery has been exploited recently to treat hearing loss, as this method can both bypass the blood-labyrinth barrier and provide sustained drug release. Combined drug microcrystals (MCs) offer additional advantages for sensorineural hearing loss treatment via intratympanic (IT) injection due to their shape effect and combination strategy. In this study, to endow viscous effects of hydrogels, nonspherical dexamethasone (DEX) and lipoic acid (LA) MCs were incorporated into silk fibroin (SF) hydrogels, which were subsequently administered to the tympanic cavity to investigate their pharmaceutical properties. First, we prepared DEX and LA MCs by a traditional precipitation technique followed by SF hydrogel incorporation (SF+DEX+LA). After characterization of the physicochemical features, including morphology, rheology, and dissolution, both a suspension of combined DEX and LA MCs (DEX+LA) and SF+DEX+LA were administered to guinea pigs by IT injection, after which the pharmacokinetics, biodegradation and biocompatibility were evaluated. To our surprise, compared to the DEX+LA group, the pharmacokinetics of the SF+DEX+LA hydrogel group did not improve significantly, which may be ascribed to their nonspherical shape and deposition effects of the drugs MCs. The cochlear tissue in each group displayed good morphology, with no obvious inflammatory reactions. This combined MC suspension has the clear advantages of no vehicle, easy scale-up preparation, and good biocompatibility and outcomes, which paves the way for practical treatment of hearing loss via local drug delivery.

High-Density Dynamic Bonds Cross-Linked Hydrogel with Tissue Adhesion, Highly Efficient Self-Healing Behavior, and NIR Photothermal Antibacterial Ability as Dressing for Wound Repair.

Multifunctional hydrogels with tissue adhesion, self-healing behavior, and antibacterial properties have potential in wound healing applications. However, their inefficient self-healing behavior and antibacterial agents can cause long-term cytotoxicity and drug resistance, considerably limiting their clinical use. Herein, we reported a PDA@LA hydrogel constructed by introducing polydopamine nanoparticles (PDA-NPs) into a high-density dynamic bonds cross-linked lipoic acid (LA) hydrogel that was formed by the polymerization of LA. Because of its rich carboxyl groups, the LA hydrogel could adhere firmly to various tissues. Owing to the high-density dynamic bonds, the cut LA hydrogel exhibited highly inefficient self-healing behavior and recovered to its uncut state after self-healing for 10 min. After the introduction of the PDA-NPs, the hydrogel was able to heat up to more than 40 °C to kill approximately 100% of the Escherichia coli and Staphylococcus aureus under near-infrared (NIR) laser, thus resisting wound infections. Because no toxic antibacterial agent was used, the PDA@LA hydrogel caused mild long-term cytotoxicity or drug resistance. Consequently, the adhesive, highly efficient self-healing, and NIR photothermal antibacterial PDA@LA hydrogel exhibits considerable potential for clinical use.

Impact of combined alpha-lipoic acid and mitoquinone supplementation on myocardial infarction in aged rats: Heart performance and molecular mechanisms.

BACKGROUND: This study aimed to investigate the effects of combined alpha-lipoic acid (ALA) and mitoquinone (Mito Q) supplementation on cardiac function and the underlying mechanisms in aged rats with myocardial infarction (MI). METHODS: The aged rats underwent left anterior descending artery (LADA) occlusion for 30 min, followed by reperfusion for 24 h. ALA (100 mg/kg, gavage) and Mito Q (10 mg/kg, IP) were administered daily for two weeks before ischemia. Cardiac function, inflammatory, and apoptotic markers were evaluated 24 h after ischemia. RESULTS: The results of this study indicated that the administration of the combination of ALA and Mito Q significantly improved cardiac function. This improvement was linked to a reduction in the expression of pro-inflammatory cytokines TNF-α, IL-6, and IL-1ß (P < 0.001) and apoptotic markers (Bax, caspase-3, and Cyt-c), as well as a decrease in the percentage of TUNEL-positive cells (P < 0.001). CONCLUSION: The study revealed that combined intervention synergistically mitigated cardiac dysfunction by suppressing inflammatory and apoptotic pathways in aged rats with MI. Further research is needed to validate the potential of ALA and Mito Q as therapeutic options for elderly people at risk of heart attacks.

Dietary lipoic acid alleviates autism-like behavior induced by acrylamide in adolescent mice: the potential involvement of the gut-brain axis.

Consuming fried foods has been associated with an increased susceptibility to mental health disorders. Nevertheless, the impact of alpha-lipoic acid (α-LA, LA) on fried food-induced autism-like behavior remains unclear. This study aimed to explore how LA affects autism-related behavior and cognitive deficits caused by acrylamide in mice, a representative food hazard found in fried foods. This improvement was accomplished by enhanced synaptic plasticity, increased neurotrophin expression, elevated calcium-binding protein D28k, and restored serotonin. Additionally, LA substantially influenced the abundance of bacteria linked to autism and depression, simultaneously boosted short-chain fatty acid (SCFA) levels in fecal samples, and induced changes in serum amino acid concentrations. In summary, these findings suggested that exposure to acrylamide in adolescent mice could induce the development of social disorders in adulthood. LA showed promise as a nutritional intervention strategy to tackle emotional disorders during adolescence.

Biodegradable Lipid-Modified Poly(Guanidine Thioctic Acid)s: A Fortifier of Lipid Nanoparticles to Promote the Efficacy and Safety of mRNA Cancer Vaccines.

Lipid nanoparticles (LNPs)-based messenger RNA (mRNA) therapeutics have emerged with promising potentials in the fields of infectious diseases, cancer vaccines, and protein replacement therapies; however, their therapeutic efficacy and safety can still be promoted by the optimization of LNPs formulations. Unfortunately, current LNPs suffer from increased production of reactive oxygen species during translation, which leads to a decreased translation efficiency and the onset of inflammation and other side effects. Herein, we synthesize a lipid-modified poly(guanidine thioctic acid) polymer to fabricate novel LNPs for mRNA vaccines. The acquired G-LNPs significantly promote the translation efficiency of loaded mRNA and attenuate inflammation after vaccination through the elimination of reactive oxygen species that are responsible for translational inhibition and inflammatory responses. In vivo studies demonstrate the excellent antitumor efficacy of the G-LNPs@mRNA vaccine, and two-dose vaccination dramatically increases the population and infiltration of cytotoxic T cells due to the intense antitumor immune responses, thus generating superior antitumor outcomes compared with the mRNA vaccine prepared from traditional LNPs. By synergy with immune checkpoint blockade, the tumor inhibition of G-LNPs@mRNA is further boosted, indicating that G-LNPs-based mRNA vaccines will be powerful and versatile platforms to combat cancer.

Alpha-lipoic acid improves cryopreservation of rooster semen by reducing oxidative stress.

Inhibiting oxidative stress is key for ensuring sperm motility during semen cryopreservation. The aim of this study was to investigate the effect of adding alpha-lipoic acid (ALA) as an extender in rooster semen cryopreservation. Different concentrations of ALA were added to the frozen diluent of rooster semen; subsequently, computer-aided semen analysis was used to determine membrane functional integrity, acrosome integrity, antioxidant capacity (based on T-AOC, GSH-Px, SOD, CAT, and MDA contents), and mitochondrial integrity. The frozen sperm ultrastructure was observed using transmission electron microscopy. The results showed that the addition of different concentrations of ALA partially to greatly improved the quality of frozen sperm; in particular, 8 µg/mL ALA significantly improved multiple parameters of sperm quality, including sperm motility and antioxidant enzyme activity, after freeze-thaw. The results of this study provide empirical and theoretical support for effective rooster semen cryopreservation and can inform the development of new protective agents in the field of livestock reproduction.

Clinically Effective Molecules of Natural Origin for Obesity Prevention or Treatment.

The prevalence and incidence of obesity and the comorbidities linked to it are increasing worldwide. Current therapies for obesity and associated pathologies have proven to cause a broad number of adverse effects, and often, they are overpriced or not affordable for all patients. Among the alternatives currently available, natural bioactive compounds stand out. These are frequently contained in pharmaceutical presentations, nutraceutical products, supplements, or functional foods. The clinical evidence for these molecules is increasingly solid, among which epigallocatechin-3-gallate, ellagic acid, resveratrol, berberine, anthocyanins, probiotics, carotenoids, curcumin, silymarin, hydroxy citric acid, and α-lipoic acid stand out. The molecular mechanisms and signaling pathways of these molecules have been shown to interact with the endocrine, nervous, and gastroenteric systems. They can regulate the expression of multiple genes and proteins involved in starvation-satiety processes, activate the brown adipose tissue, decrease lipogenesis and inflammation, increase lipolysis, and improve insulin sensitivity. This review provides a comprehensive view of nature-based therapeutic options to address the increasing prevalence of obesity. It offers a valuable perspective for future research and subsequent clinical practice, addressing everything from the molecular, genetic, and physiological bases to the clinical study of bioactive compounds.