ALA Treatment Research Articles

Analysis of the Transcriptome Provides Insights into the Photosynthate of Maize Response to Salt Stress by 5-Aminolevulinic Acid.

Salt stress is a significant environmental factor that impedes maize growth and yield. Exogenous 5-aminolevulinic acid (ALA) has been shown to mitigate the detrimental effects of various environmental stresses on plants. However, its regulatory role in the photosynthesis mechanisms of maize seedlings under salt stress remains poorly understood. Transcriptome sequencing and physiological index measurements were conducted on the leaves of the "Zhengdan 958" cultivar subjected to three different treatments. Differential expression analysis revealed 4634 differentially expressed genes (DEGs), including key transcription factor (TF) families such as NAC, MYB, WRKY, and MYB-related, across two comparisons (SS_vs_CK and ALA_SS_vs_SS). Significant enrichment was observed in the metabolic pathways related to porphyrin metabolism, photosynthesis-antenna proteins, photosynthesis, and carbon fixation in photosynthetic organisms. ALA treatment modulated the expression of photosynthesis-related genes, increased photosynthetic pigment content, and enhanced the activities of superoxide dismutase (SOD) and catalase (CAT), thereby mitigating the excessive accumulation of reactive oxygen species (ROS). Furthermore, ALA increased starch content under salt stress. These findings establish a foundational understanding of the molecular mechanisms through which ALA regulates photosynthesis under salt stress in maize seedlings. Collectively, exogenous ALA enhances maize's salt tolerance by regulating photosynthesis-related pathways.

Ferroptosis in the Substantia Nigra Pars Compacta of Mice: Triggering Role of Ultrafine Diesel Exhaust Particles and Mitigation by α-Lipoic Acid.

Recent epidemiological and experimental studies have increasingly highlighted the association between environmental pollution, especially ultrafine particulate matter (PM), and the risk of neurodegenerative diseases, such as Parkinson's disease (PD). These previous studies suggest a potential mechanism by which ultrafine PM contributes to neuronal damage through processes, such as iron accumulation and oxidative stress. In this study, we aimed to elucidate the effects of ultrafine PM on ferroptosis, an iron-dependent form of cell death, in the mouse substantia nigra pars compacta (SNc) and to evaluate the protective role of α-lipoic acid (ALA). Mice were exposed to ultrafine diesel exhaust particles (ufDEP), a type of ultrafine PM, intranasally and injected ALA intraperitoneally for seven consecutive days. Iron accumulation and lipid peroxidation were significantly increased, and antioxidant capacity was significantly decreased in the SNc after ufDEP exposure, highlighting the deleterious effects of ufDEP on tyrosine hydroxylase (TH)-positive neurons. In contrast, ALA treatment effectively mitigated these effects by reducing iron accumulation, decreasing lipid peroxidation, and restoring antioxidant levels, resulting in the protection of TH-positive neurons from ferroptotic damage. Our results provide evidence that ufDEP can induce ferroptosis in dopaminergic neurons in the SNc, potentially contributing to PD pathogenesis. Furthermore, ALA showed protective effects against ufDEP-induced ferroptotic damage, suggesting its potential as a therapeutic intervention for PD.

Renal and Vascular Functional Decline in Aged Low Birth Weight Murine Adults

Introduction: Maternal undernutrition (MUN)-induced low birth weight (LBW) neonates are susceptible to the development of high blood pressure and kidney disease later in life, although the underlying pathological causes remain unclear. The study here investigated the role of renal oxidative stress, impairment of vascular function, and altered sensitivity to angiotensin II (Ang II) as factors that contribute to these pathologies in aged LBW mice. Methods: LBW offspring were generated using a combined protein and caloric restricted MUN mouse model. The resulting LBW offspring were examined 1 year after birth for mean arterial blood pressure (MABP) (carotid artery catheterization), renal blood flow (RBF) (laser Doppler flowmetry), glomerular filtration rate (GFR) (sinistrin clearance), vasoreactivity (myograph), renal vascular density (CD31 staining), and reactive oxygen species (ROS) (ROS probes). Immunoblotting examined Ang II type 1 receptor (AT1R), soluble guanylate cyclase (sGC), and antioxidant systems. Pharmacological agents delivered to animals included the sGC stimulator δ-aminolevulinic acid (ALA), the AT1R inhibitor losartan, the antioxidant ethyl pyruvate (EP), and the toll-like receptor 4 inhibitor TAK242. Results: After 1 year, MABP was increased, while RBF, GFR, vascular reactivity, renal vascular density, and sGC were all reduced in the LBW aged adult. All four pharmacological agents improved MABP, RBF, GFR, vascular density, and vascular reactivity. Renal ROS was increased in the LBW adult but was reduced by ALA, EP, and TAK242 treatment. AT1R was upregulated in the LBW adult, while sGC was decreased, an effect reversed by ALA treatment. Endogenous antioxidant systems, including SOD1, catalase, and glutathione were downregulated in the LBW adult. Conclusion: MUN-induced LBW mice experience increased Ang II sensitivity and oxidative stress. The increased Ang II sensitivity and ROS generation influences vascular density and reactivity, which drive an increase in MABP, and a concomitantly decrease in RBF and glomerular filtration. Pharmacological intervention that inhibits AT1R, enhances levels of sGC, reduces ROS, or inhibits toll-like receptor 4 improves vascular and renal function in the LBW adult.

Exogenous 5-aminolevulinic acid promotes carotenoid accumulation in tomato fruits by regulating ethylene biosynthesis and signaling.

5-Aminolevulinic acid (ALA) can not only improve fruit yield and quality, but also increase the lycopene content in tomato fruits. Furthermore, ALA has been shown to promote system-2 ethylene production in tomato fruits. However, the specific interactions between ALA and ethylene during fruit ripening remain unclear. In this study, we treated tomato fruits with ALA, 1-aminocyclopropane-1-carboxylic acid (ACC), aminooxyacetic acid (AOA) + AgNO3, and AOA + AgNO3 + ALA and analyzed ethylene emissions, carotenoid contents, and the relative gene expression levels related to fruit ripening, carotenoid contents, ethylene synthesis, and signal transduction. The ALA treatment significantly enhanced ethylene bursts and carotenoid accumulation, and significantly upregulated the expression of ethylene and carotenoid-related genes, such as SlACS2, SlACS4, SlACO1, SlPSY1, and SlPDS. We also observed that the gene expression levels associated with carotenoid synthesis were downregulated in fruits treated with a combination of ethylene inhibitors (AOA + AgNO3). However, there was a significant upregulation in the gene expression levels associated with carotenoid synthesis and an increase in carotenoid content when fruits were treated with AOA + AgNO3 + ALA. After silencing SlACO1 expression, the total carotenoid content and SlPSY1 expression decreased significantly, while this effect was reversed after exogenous application of ALA. These results indicated that ALA promotes carotenoid accumulation in tomato fruits by promoting ethylene biosynthesis. In conclusion, our results highlighted the role of ALA in promoting carotenoid accumulation and ripening in tomato fruits by regulating ethylene synthesis, thereby providing a novel strategy for improving fruit quality.

α-Linolenic acid promotes testosterone synthesis by improving mitochondrial function in primary rooster Leydig cells

The present study aimed to investigate the direct effects of α-Linolenic acid (ALA) on the in vitro production of testosterone and the expression of key enzymes and proteins related to steroidogenesis in Leydig cells of roosters. MethodsPurified primary Leydig cells isolated from 65-week-old roosters were purified and treated with different concentrations of ALA treatments: (0 μm/L [control], solvent control group (DMSO), 20 μM/L, 40 μM/L, and 80 μM/L) and cell counting-8 (CCK-8) for cell viability assay, Enzyme-linked immunosorbent assay (ELISA) kit for the determination of testosterone in cell supernatants, quantitative (real-time) PCR, and analysis of activities of antioxidants catalase (CAT), superoxide dismutase (SOD) and malondialdehyde (MDA), evaluation of mitochondrial membrane potential, pro- and anti-apoptotic proteins/genes Bcl-2, Bcl-2-associated X protein (Bax), apoptosis-inducing factor (AIF) were done respectively. ResultsOur results showed that ALA significantly increased testosterone secretion in primary rooster Leydig cells (P < 0.05), and 40 μM/L is the optimal dose. Leydig cells supplemented with ALA (20, 40, 80 μM) increased the expression of key enzymes and proteins 3β-hydroxysteroid dehydrogenase (3β-HSD), steroidogenic acute regulatory protein (StAR), cholesterol side-chain cleavage enzyme (P450scc) concerning steroidogenesis, enhanced antioxidant capability, improved mitochondrial biogenesis, and markedly improved the mitochondrial membrane potential (P < 0.05). Furthermore, the expression of the apoptosis-suppressive gene Bcl-2 was significantly increased, but Bax and AIF expression was decreased in the ALA group compared to that in the control group (P < 0.05). ConclusionALA promoted testosterone production, enhanced steroidogenic enzyme expression, improved mitochondrial function, and antioxidant capacity, and reduced apoptosis in primary rooster Leydig cells, with 40 μM/L identified as the optimal concentration.

Exogenous 5-aminolevulinic acid enhanced saline-alkali tolerance in pepper seedlings by regulating photosynthesis, oxidative damage, and glutathione metabolism.

A plant growth regulator, 5-aminolevulinic acid, enhanced the saline-alkali tolerance via photosynthetic, oxidative-reduction, and glutathione metabolism pathways in pepper seedlings. Saline-alkali stress is a prominent environmental problem, hindering growth and development of pepper. 5-Aminolevulinic acid (ALA) application effectively improves plant growth status under various abiotic stresses. Here, we evaluated morphological, physiological, and transcriptomic differences in saline-alkali-stressed pepper seedlings after ALA application to explore the impact of ALA on saline-alkali stress. The results indicated that saline-alkali stress inhibited plant growth, decreased biomass and photosynthesis, altered the osmolyte content and antioxidant system, and increased reactive oxygen species (ROS) accumulation and proline content in pepper seedlings. Conversely, the application of exogenous ALA alleviated this damage by increasing the photosynthetic rate, osmolyte content, antioxidant enzyme activity, and antioxidants, including superoxide dismutase, catalase, glutathione reductase, and glutathione peroxidase, and reducing glutathione to reduce ROS accumulation and malonaldehyde content. Moreover, the transcriptomic analysis revealed the differentially expressed genes were mainly associated with photosynthesis, oxidation-reduction process, and glutathione metabolism in saline-alkali stress + ALA treatment compared to saline-alkali treatment. Among them, the change in expression level in CaGST, CaGR, and CaGPX was close to the variation of corresponding enzyme activity. Collectively, our findings revealed the alleviating effect of ALA on saline-alkali stress in pepper seedlings, broadening the application of ALA and providing a feasible strategy for utilize saline-alkali soil.

Targeted regulation of 5-aminolevulinic acid enhances flavonoids, anthocyanins and proanthocyanidins accumulation in Vitis davidii callus

BackgroundSpine grape (Vitis davidii) is a promising source of high-quality anthocyanins, with vast potential for application in food, pharmaceutical, and cosmetic industries. However, their availability is limited by resource constraints. Plant cell culture has emerged as a valuable approach for anthocyanin production and serves as an ideal model to investigate the regulation of anthocyanin biosynthesis. Elicitors are employed to achieve targeted enhancement of anthocyanin biosynthesis. The present study investigated the impact of 5-aminolevulinic acid (ALA) as an elicitor on the accumulation of anthocyanins and flavonoids during spine grape callus growth. Specifically, we examined the effects of ALA on anthocyanin and its component accumulation in callus, and biosynthetic anthocyanin gene expression.ResultsALA at 25 µg/L increased the biomass of spine grape callus. ALA induction enhanced the levels of flavonoids, anthocyanins and proanthocyanidins in callus, with maximum values reaching 911.11 mg/100 g DW, 604.60 mg/100 g DW, and 5357.00 mg/100 g DW, respectively, after callus culture for 45 days. Notably, those levels were 1.47-, 1.93- and 1.83-fold higher than controls. ALA induction modulated the flavonoid profile, and among 97 differential flavonoid metabolites differing from controls, 77 were upregulated and 20 were downregulated. Six kinds of anthocyanins, namely cyanidin (8), delphinidin (6), peonidin (5), malvidin (4), petunidin (3) and pelargonidin (3), were detected in callus, with peonidin most abundant. Compared with controls, anthocyanin components were increased in ALA-treated callus. The key genes PAL1, PAL2, PAL4, CHI, CHS3, F3’H, F3H, FLS, DFR, UFGT, MYBA1, LDOX, OMT3, GT1 and ACT involved in anthocyanin biosynthesis were upregulated following ALA treatment, resulting in anthocyanin accumulation.ConclusionThis study revealed a novel mode of ALA-mediated promotion of plant anthocyanin biosynthesis and accumulation at the cellular level, and a strategy for enhancing anthocyanin content in spine grape callus. The findings advance commercial-scale production of anthocyanins via spine grape callus culture. we also explored the accumulation patterns of flavonoids and anthocyanins under ALA treatment. Augmentation of anthocyanins coincided with elevated expression levels of most genes involved in anthocyanin biosynthesis within spine grape callus following ALA treatment.

Iron Metabolism in Aminolevulinic Acid-Photodynamic Therapy with Iron Chelators from the Thiosemicarbazone Group.

Iron plays a crucial role in various metabolic processes. However, the impact of 5-aminolevulinic acid (ALA) in combination with iron chelators on iron metabolism and the efficacy of ALA-photodynamic therapy (PDT) remain inadequately understood. This study aimed to examine the effect of thiosemicarbazone derivatives during ALA treatment on specific genes related to iron metabolism, with a particular emphasis on mitochondrial iron metabolism genes. In our study, we observed differences depending on the cell line studied. For the HCT116 and MCF-7 cell lines, in most cases, the decrease in the expression of selected targets correlated with the increase in protoporphyrin IX (PPIX) concentration and the observed photodynamic effect, aligning with existing literature data. The Hs683 cell line showed a different gene expression pattern, previously not described in the literature. In this study, we collected an extensive analysis of the gene variation occurring after the application of novel thiosemicarbazone derivatives and presented versatile and effective compounds with great potential for use in ALA-PDT.

Heme deficiency in skeletal muscle exacerbates sarcopenia and impairs autophagy by reducing AMPK signaling

Heme serves as a prosthetic group in hemoproteins, including subunits of the mammalian mitochondrial electron transfer chain. The first enzyme in vertebrate heme biosynthesis, 5-aminolevulinic acid synthase 1 (ALAS1), is ubiquitously expressed and essential for producing 5-aminolevulinic acid (ALA). We previously showed that Alas1 heterozygous mice at 20–35 weeks (aged-A1+/−s) manifested impaired glucose metabolism, mitochondrial malformation in skeletal muscle, and reduced exercise tolerance, potentially linked to autophagy dysfunction. In this study, we investigated autophagy in A1+/−s and a sarcopenic phenotype in A1+/−s at 75–95 weeks (senile-A1+/−s). Senile-A1+/−s exhibited significantly reduced body and gastrocnemius muscle weight, and muscle strength, indicating an accelerated sarcopenic phenotype. Decreases in total LC3 and LC3-II protein and Map1lc3a mRNA levels were observed in aged-A1+/−s under fasting conditions and in Alas1 knockdown myocyte-differentiated C2C12 cells (A1KD-C2C12s) cultured in high- or low-glucose medium. ALA treatment largely reversed these declines. Reduced AMP-activated protein kinase (AMPK) signaling was associated with decreased autophagy in aged-A1+/−s and A1KD-C2C12s. AMPK modulation using AICAR (activator) and dorsomorphin (inhibitor) affected LC3 protein levels in an AMPK-dependent manner. Our findings suggest that heme deficiency contributes to accelerated sarcopenia-like defects and reduced autophagy in skeletal muscle, primarily due to decreased AMPK signaling.

MdWRKY71 as a positive regulator involved in 5-aminolevulinic acid-induced salt tolerance in apple

5-Aminolevulinic acid (ALA), is a novel plant growth regulator that can enhance plant tolerance against salt stress. However, the molecular mechanism of ALA is not well studied. In this study, ALA improved salt tolerance of apple (Malus × domestica 'Gala') when the detached leaves or cultured calli were used as the materials. The expression of MdWRKY71, a WRKY transcription factor (TF) gene was found to be responsive to NaCl as well as ALA treatment. Functional analysis showed that overexpressing (OE)-MdWRKY71 significantly improved the salt tolerance of the transgenic apple, while RNA interfering (RNAi)-MdWRKY71 reduced the salt tolerance. However, exogenous ALA alleviated the salt damage in the RNAi-MdWRKY71 apple. When MdWRKY71 was transferred into tobacco, the salt tolerance of transgenic plants was enhanced, which was further improved by exogenous ALA. Subsequently, MdWRKY71 bound to the W-box of promoters of MdSOS2, MdNHX1, MdCLC-g, MdSOD1, MdCAT1 and MdAPX1, transcriptionally activating the gene expressions. Since the genes are responsible for Na+ and Cl− transport and antioxidant enzyme activity respectively, it can be concluded that MdWRKY71, a new TF, is involved in ALA-improved salt tolerance by regulating ion homeostasis and redox homeostasis. These results provided new insights into the transcriptional regulatory mechanism of ALA in enhancing apple salt tolerance.

ALA Promotes Sucrose Accumulation in Early Peach Fruit by Regulating SPS Activity.

5-Aminolevulinic acid (ALA), as a novel plant growth regulator, is a critical precursor for the biosynthesis of porphyrin compounds in all organisms. Many studies have reported that exogenous ALA treatment could improve fruit sweetness. However, the mechanism by which ALA promotes the increase in sugar content in fruit remains unclear. In this study, we found that ALA significantly promoted sucrose accumulation and SPS (sucrose phosphate synthase) activity in peach fruit. At 14, 28, 42, 50 and 60 days after ALA treatment, sucrose content of fruit was increased by 23%, 43%, 37%, 40% and 16%, respectively, compared with control treatment, and SPS enzyme activity was increased by 21%, 28%, 47%, 37% and 29%, respectively. Correlation analysis showed that the sucrose content of peach fruit under ALA treatment was significantly positively correlated with SPS activity. Subsequently, bioinformatics was used to identify SPS gene family members in peach fruit, and it was found that there were four members of the PpSPS gene family, distributed on chromosomes 1, 7 and 8, named PpSPS1, PpSPS2, PpSPS3 and PpSPS4, respectively. The results of qRT-PCR showed that PpSPS2 and PpSPS3 were highly expressed in response to ALA during fruit development, and the expression of PpSPS2 was positively correlated with SPS activity and sucrose accumulation in peach fruit. The results of tobacco subcellular localization showed that PpSPS2 was mainly distributed in the cytoplasm and nucleus, while PpSPS3 was mainly distributed in the nucleus. The results of this study will lay the foundation for further study on the functions of PpSPS and the regulation of sugar metabolism during the development and ripening of peach fruit by ALA.

Effect of foliar applications of aminolevulinic acid (bulk and nano-encapsulated) on bell pepper under heat stress

Plant growth and production can be adversely affected by high temperature stress, which is defined as an increase in temperature over a threshold level. 5-aminolevulinic acid (ALA) can be used as a beneficial growth regulator in agriculture, particularly for plants experiencing abiotic stress. The efficacy of exogenous two form ALA application (bulk and nanoencapsulated) was investigated in a factorial experiment based on a completely randomized block design with 12 replications. In this study, different temperatures (optimal temperature 25 °C, and high temperature 35 °C) and different ALA treatments were used (control, 1 mM of ALA, and 1 mM Nano-encapsulated N-ALA). The study revealed that elevated temperatures of 35 °C had an adverse impact on the majority of bell pepper growth characteristics. Nevertheless, the application of ALA and N-ALA significantly enhanced the growth characteristics under these conditions. In contrast to the conditions at 25 °C, the concentrations of potassium (K), proline, electrolyte leakage (EL), glucose, and fructose exhibited an increase at 35 °C. However, both forms of ALA were effective in mitigating these adverse effects. Comparatively, the control treatment showed elevated levels of peroxidase (POD), superoxide dismutase (SOD), and catalase (CAT) enzymes, along with increased malondialdehyde (MDA) levels compared to the ALA treatment. The treatment with ALA resulted in the highest fresh weight and shoot length at 35 °C compared to N-ALA. Conversely, at the same temperature, N-ALA led to a 17 % increase in chlorophyll fluorescence and a 32 % increase in DPPH compared to ALA. In summary, the application of both ALA and Nano-encapsulated N-ALA effectively mitigates the adverse effects of exposure to 35 °C on bell pepper growth and biochemical parameters.

The protective effects of alamandine on angiotensin II-induced cardiac dysfunction and remodeling in rats

Alamandine (Ala), a relatively recent addition to the renin-angiotensin system (RAS), is a heptapeptide sharing structural similarities with angiotensin-(1-7). This peptide has garnered significant attention due to its distinctive antihypertensive, vasodilatory, and antifibrotic effects. In this study, we sought to determine whether Ala acts as a counter-regulatory agent against angiotensin II-induced cardiac hypertrophy, fibrosis, and inflammation in rats. Male SD rats (n=6 in each group) received a two-week subcutaneous infusion of vehicle (saline), angiotensin II (ANG II, 150 ng/kg/min), or a combination of ANG II and Ala (50 ng/kg/min) via mini osmotic pumps. Left ventricular (LV) function was evaluated through echocardiography. Histological analysis of cardiac hypertrophy and fibrosis was conducted using Hematoxylin Eosin and Trichome-Mason staining, respectively. Compared to the vehicle group, treatment with Ala significantly (*p&lt;0.05) attenuated ANG II-induced cardiac mass (659.27 ± 54.26* vs. 824.48 ± 40.38 mg) with reduced LV thickness and end-diastolic volume. Ala treatment also improved cardiac function, as indicated by reduced global longitudinal strain and myocardial performance index. Histological images revealed that Ala treatment markedly reduced cardiomyocyte area (383.63* ± 7.20 vs 490.59 ± 13.13 μm²) and fibrosis area (5.22* ± 0.93 vs. 9.64 ± 0.36%) in rats treated with ANG II, along with reduced mRNA expression of pro-hypertrophic markers such as brain natriuretic peptide (4.29 ± 0.50* vs 7.53 ± 0.68, fold change) and β-myosin heavy chain (6.11 ± 0.61* vs 10.29 ± 1.02), as well as pro-fibrosis markers collagen 1 (5.72 ± 0.59* vs 10.56 ± 1.69), fibronectin (2.18 ± 0.34* vs 4.69 ± 0.70), and α-smooth muscle actin (2.14 ± 0.42* vs 3.85 ± 0.06), when compared to the rats treated with ANG II alone. Flow cytometry analysis also showed that Ala treatment significantly reduced ANG II-induced immune responses in the heart by reducing immune cell populations including CD4, CD8 T cells, B cells and NK cells, and increasing presence of anti-inflammatory M2 monocytes. Additionally, the mRNA levels of interlukin-6, CD 68, and chemokine monocyte chemoattractant protein-1 were significantly decreased in Ala-treated rats. Furthermore, treatment with Ala reversed ANG II-induced alterations in the mRNA expression of angiotensin-converting enzyme (ACE, 2.05 ± 0.16* vs. 3.08 ± 0.25), angiotensin type 1 receptor (1.45 ± 0.22* vs. 2.56 ± 0.31), and ACE 2 (1.08 ± 0.10** vs. 0.38 ± 0.06) in the LV of the heart. Taken together, these findings demonstrate that alamandine exerts a protective effect against ANG II-induced cardiac dysfunction, hypertrophy, fibrosis, and inflammation, potentially acting as a protective component of the RAS to counteract the adverse effects of ANG II. Alamandine might be a potential therapeutic agent in the treatment of cardiovascular disorders. Supported by NIH grants R01 HL139521 &amp; 155091. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Efficacy of Using Alpha-Lipoic Acid Supplement in Patients with Diabetic Neuropathy: A Meta-Analysis and Systematic Review

Background: In the 21st century, diabetes mellitus and its complications have become the most common health-care problem. The most common complication is diabetic neuropathy. Many drugs were tried to alleviate the neurological symptoms, whereas Alpha-lipoic acid has proven its effectiveness.Aim: we aim in our study to assess the efficacy of Alpha-lipoic acid versus other lines in diabetic patients complicated with neuropathy.Methods: We searched online databases such as (PubMed, Scopus, WOS, and Cochrane Library) for related randomized clinical trials (RCTs). Retrieved articles were screened, and relevant studies were included in a meta-analysis. Continuous data were pooled as mean difference (MD) with 95% confidence interval (CI), and dichotomous data were pooled as relative risk (RR) and 95% CI. Analysis was conducted using RevMan software (Version 5.4). Our primary outcome was the alleviation of neurological symptoms, while the 2ry outcome was the occurrence of adverse events.Results: four RCTs (358 cases) were included. ALA treatment produced favorable results for TSS (a dose-related trend was observed), NDS. ALA treatment resulted in a dose-dependent response relative to the placebo for TSS and the global satisfaction score. The use of ALA to prevent neurological symptoms should be further researched.Conclusion: Alpha-lipoic acid has a satisfactory effect on neurological symptoms, there was a marked decrease in sensory symptoms.

Study on the Mechanism of Exogenous 5-Aminolevulinic Acid (ALA) in Regulating the Photosynthetic Efficiency of Pear Leaves

To provide a theoretical basis for the application of ALA in pear production, the effects of exogenous 5-aminolevulinic acid (ALA) treatment on leaf photosynthetic gas exchange parameters, chlorophyll fast fluorescence properties, and relative expression of the related genes were investigated using pear (Pyrus pyrifolia Nakai cv. ‘Whasan’) as a material in the study. The results show that exogenous ALA treatment improved the photosynthetic gas exchange parameters of pear leaves, upregulated the expression of multiple key genes which are related to ALA biosynthesis, metabolism, and transformation into chlorophylls. GUS staining in tobacco leaves showed that exogenous ALA activated the promoter activity of PypHEMA and PypCHLH genes, implying that the synthesis of endogenous ALA and chlorophylls was promoted by exogenous ALA. Furthermore, ALA promoted the expression of the genes encoding photosystem II (PSII) reaction center proteins, such as core protein D1, inner light-harvesting pigment proteins CP43 and CP47, and cytochrome b559. This led to increased PSII reaction center activity. In addition, ALA alleviated the donor side oxygen-evolving complex inhibition and reduced the closure rate on the receptor side, allowing for increased photochemical electron transfer and reduced heat dissipation while improving the photosynthetic performance index PIabs and PItotal. The findings of this study contribute to a better understanding of ALA’s promotion of plant photosynthetic efficiency, providing valuable insights for further research and potential applications in pear production.

The beneficial effect of α-lipoic acid on spinal cord injury repair in rats is mediated through inhibition of oxidative stress: A transcriptomic analysis

Background Oxidative stress is a crucial factor contributing to the occurrence and development of secondary damage in spinal cord injuries (SCI), ultimately impacting the recovery process. α-lipoic acid (ALA) exhibits potent antioxidant properties, effectively reducing secondary damage and providing neuroprotective benefits. However, the precise mechanism by which ALA plays its antioxidant role remains unknown. Methods We established a model of moderate spinal cord contusion in rats. Experimental rats were randomly divided into 3 distinct groups: the sham group, the model control group (SCI_Veh), and the ALA treatment group (SCI_ALA). The sham group rats were exposed only to the SC without contusion injury. Rats belonging to SCI_Veh group were not administered any treatment after SCI. Rats of SCI_ALA group were intraperitoneally injected with the corresponding volume of ALA according to body weight for three consecutive days after the surgery. Subsequently, three days after SCI, spinal cord samples were obtained from three groups of rats: the sham group, model control group, and administration group. Thereafter, total RNA was extracted from the samples and the expression of three sets of differential genes was analyzed by transcriptome sequencing technology. Real-time PCR was used to verify the sequencing results. The impact of ALA on oxidative stress in rats following SCI was assessed by measuring their total antioxidant capacity and hydrogen peroxide (H2O2) content. The effects of ALA on rat recovery following SCI was investigated through Beattie and Bresnahan (BBB) score and footprint analysis. Results The findings from the transcriptome sequencing analysis revealed that the model control group had 2975 genes with altered expression levels when compared to the ALA treatment group. Among these genes, 1583 were found to be upregulated while 1392 were down-regulated. Gene ontology (GO) displayed significant enrichment in terms of functionality, specifically in oxidative phosphorylation, oxidoreductase activity, and signaling receptor activity. The Kyoto encyclopedia of genes and genomes (KEGG) pathway was enriched in oxidative phosphorylation, glutathione metabolism and cell cycle. ALA was found to have multiple benefits for rats after SCI, including increasing their antioxidant capacity and reducing H2O2 levels. Additionally, it was effective in improving motor function (such as 7 days after SCI, the BBB score for SCI_ALA was 8.400 ± 0.937 compared to 7.050 ± 1.141 for SCI_Veh) and promoting histological recovery after SCI (The results of HE demonstrated that the percentage of damage area in was 44.002 ± 6.680 in the SCI_ALA and 57.215 ± 3.964 in the SCI_Veh at the center of injury.). The sequence data from this study has been deposited into Sequence Read Archive (https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE242507). Conclusion Overall, the findings of this study confirmed the beneficial effects of ALA on recovery in SCI rats through transcriptome sequencing, behavioral, as well histology analyses.

Эффективность и токсичность индукционной терапии у пациентов с впервые диагностированным системным AL-амилоидозом: результаты проспективного одноцентрового клинического исследования

Aim. To assess the outcomes of induction therapy in patients with newly diagnosed systemic AL Amyloidosis (AL-А).&#x0D; Materials &amp; Methods. The prospective single-center clinical study enrolled 60 patients (32 women and 28 men) with newly diagnosed systemic AL-A stage I/IIIA. The median age was 59 years (range 34–74 years). In 57 patients, BorСyDex (bortezomib, cyclophosphamide, dexamethasone) was used as first-line therapy. RCd regimen (lenalidomide, cyclophosphamide, dexamethasone) was administered to 3 patients. Patients with the lack of efficacy or pronounced toxicity (n = 24) received second-line induction therapy with lenalidomide or melphalan combined with dexamethasone. High-dose chemotherapy with autologous hematopoietic stem cell transplantation (auto-HSCT) was administered to 11 (18 %) patients.&#x0D; Results. Hematologic targeted response (complete remission [CR] and very good partial remission [VGPR]) to BorCyDex was achieved in 62 % of patients. As a result of all lines of induction therapy, including auto-HSCT, targeted response increased to 69 %, specifically in 7/51 (14 %) patients with stringent CR (sCR), 8/51 (16 %) patients with CR, and 20/51 (39 %) patients with VGPR. Renal response after BorCyDex was registered in 10/38 (26 %) patients, 6/31 (19 %) patients showed heart response, and in 4/5 (80 %) patients liver response was reported. All therapy lines with auto-HSCT led to organ response (in ≥ 1 organ) in 15/46 (32 %) patients. Clinical response was shown by all patients with achieved sCR, by 67 % of patients with CR, and 47 % with VGPR (p = 0.04). With lower hematologic response rates, no clinical improvement was observed. With follow-up duration of 36 months, the median disease-free survival (without signs of hematologic and clinical progression) was not achieved. The 3-year overall survival was 80 %. Mortality during induction therapy was 10 % (6 patients died, including 2 patients with COVID-19). The planned 6 courses of BorCyDex could be completed only in 13 (23 %) out of 55 patients. During the induction therapy using BorCyDex, 4 patients died. The treatment was discontinued in 7/55 (12 %) patients due to its inefficacy and in 22/55 (39 %) patients because of severe peripheral and autonomic polyneuropathy. Nine (16 %) out of 55 patients with the achieved hematologic response showed excessive NT-proBNP elevation, which was accompanied by cardiovascular complications and provided ground for chemotherapy withdrawal.&#x0D; Conclusion. Low organ recovery rate remains the most challenging issue for AL-A treatment. Hematologic response depth (achieved CR) is a critical factor in achieving clinical effect. The obtained data confirmed high toxicity of BorCyDex regimen in AL-A patients. Despite the advances in AL-А therapy which are associated with the use of proteasome inhibitors, treatment of this disease calls for new and more effective approaches.

(+)-Lipoic acid reduces mitochondrial unfolded protein response and attenuates oxidative stress and aging in an in vitro model of non-alcoholic fatty liver disease

BackgroundNon-alcoholic fatty liver disease (NAFLD) is a liver disorder characterized by the ac-cumulation of fat in hepatocytes without alcohol consumption. Mitochondrial dysfunction and endoplasmic reticulum (ER) stress play significant roles in NAFLD pathogenesis. The unfolded protein response in mitochondria (UPRmt) is an adaptive mechanism that aims to restore mitochondrial protein homeostasis and mitigate cellular stress. This study aimed to investigate the effects of ( +)-Lipoic acid (ALA) on UPRmt, inflammation, and oxidative stress in an in vitro model of NAFLD using HepG2 cells treated with palmitic acid and oleic acid to induce steatosis.ResultsTreatment with palmitic and oleic acids increased UPRmt-related proteins HSP90 and HSP60 (heat shock protein), and decreased CLPP (caseinolytic protease P), indicating ER stress activation. ALA treatment at 1 μM and 5 μM restored UPRmt-related protein levels. PA:OA (palmitic acid:oleic acid)-induced ER stress markers IRE1α (Inositol requiring enzyme-1), CHOP (C/EBP Homologous Protein), BIP (Binding Immunoglobulin Protein), and BAX (Bcl-2-associated X protein) were significantly reduced by ALA treatment. ALA also enhanced ER-mediated protein glycosylation and reduced oxidative stress, as evidenced by decreased GPX1 (Glutathione peroxidase 1), GSTP1 (glutathione S-transferase pi 1), and GSR (glutathione-disulfide reductase) expression and increased GSH (Glutathione) levels, and improved cellular senescence as shown by the markers β-galactosidase, γH2Ax and Klotho-beta.ConclusionsIn conclusion, ALA ameliorated ER stress, oxidative stress, and inflammation in HepG2 cells treated with palmitic and oleic acids, potentially offering therapeutic benefits for NAFLD providing a possible biochemical mechanism underlying ALA beneficial effects.Graphical

5-Aminolevulinic acid treatment mitigates pesticide stress in bean seedlings by regulating stress-related gene expression and retrotransposon movements

Overdoses of pesticides lead to a decrease in the yield and quality of plants, such as beans. The unconscious use of deltamethrin, one of the synthetic insecticides, increases the amount of reactive oxygen species (ROS) by causing oxidative stress in plants. In this case, plants tolerate stress by activating the antioxidant defense mechanism and many genes. 5-Aminolevulinic acid (ALA) improves tolerance to stress by acting exogenously in low doses. There are many gene families that are effective in the regulation of this mechanism. In addition, one of the response mechanisms at the molecular level against environmental stressors in plants is retrotransposon movement. In this study, the expression levels of superoxide dismutase (SOD), ascorbate peroxidase (APX), catalase (CAT), glutathione reductase (GR), and stress-associated protein (SAP) genes were determined by Q-PCR in deltamethrin (0.5 ppm) and various doses (20, 40, and 80 mg/l) of ALA-treated bean seedlings. In addition, one of the response mechanisms at the molecular level against environmental stressors in plants is retrotransposon movement. It was determined that deltamethrin increased the expression of SOD (1.8-fold), GPX (1.4-fold), CAT (2.7-fold), and SAP (2.5-fold) genes, while 20 and 40 mg/l ALA gradually increased the expression of these genes at levels close to control, but 80 mg/l ALA increased the expression of these genes almost to the same level as deltamethrin (2.1-fold, 1.4-fold, 2.6-fold, and 2.6-fold in SOD, GPX, CAT, and SAP genes, respectively). In addition, retrotransposon-microsatellite amplified polymorphism (REMAP) was performed to determine the polymorphism caused by retrotransposon movements. While deltamethrin treatment has caused a decrease in genomic template stability (GTS) (27%), ALA treatments have prevented this decline. At doses of 20, 40, and 80 mg/L of ALA treatments, the GTS ratios were determined to be 96.8%, 74.6%, and 58.7%, respectively. Collectively, these findings demonstrated that ALA has the utility of alleviating pesticide stress effects on beans.

Nitric oxide and 5-aminolevulinic acid up-regulate growth, PS II photochemistry and antioxidant activity in UV-B stressed cyanobacterium Nostoc muscorum

The signaling molecules 5-aminolevulinic acid (ALA) and nitric oxide (NO) function as growth promoters in plants under abiotic stress. However, their roles in cyanobacteria remain unclear. This work has been attempted to examine the regulatory effects of ALA and NO (sodium nitroprusside; SNP as NO donor) against UV-B toxicity, and to investigate their interaction in regulating these effects in the cyanobacterium Nostoc muscorum ATCC 27,893. UV-B exposure (0.54 Wm−2) significantly reduced light-harvesting pigments, growth, and photosynthesis (PS-II photochemistry and oxygen evolution), while respiration rates increased considerably. Concurrently, oxidative stress biomarkers, including superoxide radical (O2•−), hydrogen peroxide (H2O2) and MDA equivalents (lipid peroxidation products), were substantially increased despite enhanced enzymatic antioxidant activity (glutathione -S- transferase, superoxide dismutase, peroxidase, and catalase). Exogenous ALA and NO mitigated the harmful UV-B impacts, leading to significant improvements in growth, pigment contents, photosynthesis, and normalization of respiration. The ALA and NO treatments further enhanced enzymatic antioxidant activity, resulting in significant reductions in O2•− and H2O2 contents, thereby minimizing UV-B induced damage to cells as evidenced by reduced lipid peroxidation rates. Moreover, supplementation of PTIO (NO scavenger) and L-NAME (NO inhibitor) reversed ALA's mitigating effect, indicating the dependency of ALA on the NO-mediated signaling process to counter UV-B stress in N. muscorum. The study suggests that SNP (NO), being cost-effective, could serve as a potent growth regulator to sustain the growth of N. muscorum, a biological nitrogen fixer and natural inhabitant of paddy fields, enabling sustainable agriculture even under unavoidable UV-B stress conditions.