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Frontiers in Bioscience (Landmark... Jun 2024L-Theanine, a nonproteinogenic amino acid derived from green tea, is being recognized as an anti-cancer candidate. However, it's roles in the development of cancer...
BACKGROUND
L-Theanine, a nonproteinogenic amino acid derived from green tea, is being recognized as an anti-cancer candidate. However, it's roles in the development of cancer chemoresistance is still unknown and the molecular mechanism is urgently to be explored.
METHODS
The effects of L-Theanine on lung cancer chemoresistance were validated by Cell Counting Kit-8 (CCK-8) assay, transwell assay, and tumor spheroid formation assay; the expression of proteins was detected by using polymerase chain reaction (PCR) and western blotting. RNA-sequencing (RNA-seq) and bioinformatics analysis were used to identify differentially expressed genes induced by L-Theanine. knockdown and overexpression were constructed by using a lentivirus-mediated transfection system.
RESULTS
L-Theanine improved the chemoresistance to -diamminedichloroplatinum (DDP) and inhibited stemness of DDP-resistant lung cancer cells but not non-resistant lung cancer cells. The results from RNA-seq analysis showed that STAT3/NOTCH1 pathway was a potential dominant signaling involved in L-Theanine improving the chemoresistance in DDP-resistant lung cancer. Mechanistically, L-Theanine impeded migration and stemness activation of DDP-resistant lung cancer cells via regulating the expression of STAT3/NOTCH1/BMAL1 signaling-induced stemness markers as well as inhibiting the expression levels of drug resistance-related genes. In addition, a combination of L-Theanine and Stat3 blockade synergistically improved the chemoresistance in DDP-resistant lung cancer.
CONCLUSION
L-Theanine improves the chemoresistance by regulating STAT3/NOTCH1/BMAL1 signaling, reducing stemness, and inhibiting the migration of DDP-resistant lung cancer cells. The finding might provide some evidence for therapeutic options in overcoming the chemoresistance in cancers, including lung cancer.
Topics: Humans; Glutamates; Drug Resistance, Neoplasm; Lung Neoplasms; Cisplatin; STAT3 Transcription Factor; Signal Transduction; Receptor, Notch1; Cell Line, Tumor; ARNTL Transcription Factors; Antineoplastic Agents; Gene Expression Regulation, Neoplastic; A549 Cells; Cell Movement
PubMed: 38940036
DOI: 10.31083/j.fbl2906226 -
Frontiers in Bioscience (Landmark... May 2024Lung cancer is the primary cause of cancer-related deaths, with one of the highest incidence and mortality rates of all malignant tumors. Dysregulated expression of...
BACKGROUND
Lung cancer is the primary cause of cancer-related deaths, with one of the highest incidence and mortality rates of all malignant tumors. Dysregulated expression of DEPDC1B has been reported to occur in various tumor types. However, the functional implications of this alteration in lung adenocarcinoma (LUAD) and the underlying molecular mechanism remains unclear. In this study, we investigated the role and clinical significance of DEPDC1B in LUAD.
METHODS
The expression of DEPDC1B in LUAD and its relationship with prognosis were systematically evaluated in several publically available datasets. The effects of DEPDC1B knockdown on the proliferation and motility of LUAD cells were assessed using the JULI Stage Real-time Cell History Recorder, while the effect of knockdown on the cell cycle was studied by flow cytometry. Furthermore, RNA-Sequencing (RNA-Seq) analysis was conducted to identify the downstream target genes and pathways regulated by DEPDC1B. Correlations between the expression of DEPDC1B and immune cell infiltration, immunotherapy resistance, and chemoresistance were also examined. Additionally, molecular biological methods were used to explore the regulatory mechanism of B-Myb on DEPDC1B expression.
RESULTS
DEPDC1B was found to be upregulated in LUAD patients and this was associated with poor clinical outcomes. Knockdown of inhibited cell growth, migration and motility, as well as cell cycle progression. Knockdown also resulted in the down-regulation of several downstream genes, including , , and , as well as the inactivation of multiple critical pathways, such as the ERK and PI3K-AKT pathways. Analysis of the tumor immuno-environment in LUAD revealed that high DEPDC1B expression was associated with an abundance of activated CD4+ memory T cells, M0 macrophages, M1 macrophages, and CD8+ T cells. Moreover, these tumors responded poorly to immunotherapy. Analysis of chemo-drug sensitivity showed that LUADs with high DEPDC1B expression were more responsive to frontline chemotherapeutic drugs such as Vinorelbine, Cisplatin, and Etoposide. Additionally, mechanistic investigations revealed that DEPDC1B is a direct target gene of B-Myb, and that its knockdown attenuated the proliferation and motility effects of B-Myb.
CONCLUSIONS
In summary, our findings indicate that DEPDC1B is a critical regulator during the malignant progression of LUAD. DEPDC1B could therefore be a promising prognostic marker and therapeutic target in LUAD diagnosis and treatment.
Topics: Humans; Adenocarcinoma of Lung; GTPase-Activating Proteins; Lung Neoplasms; Cell Proliferation; Cell Movement; Gene Expression Regulation, Neoplastic; Cell Line, Tumor; Disease Progression; Cell Cycle Proteins; Prognosis; Drug Resistance, Neoplasm; Male; Gene Knockdown Techniques; Signal Transduction; Neoplasm Proteins; Trans-Activators
PubMed: 38940035
DOI: 10.31083/j.fbl2906204 -
Frontiers in Bioscience (Landmark... Jun 2024Existing animal models for testing therapeutics in the skin are limited. Mouse and rat models lack similarity to human skin in structure and wound healing mechanism....
BACKGROUND
Existing animal models for testing therapeutics in the skin are limited. Mouse and rat models lack similarity to human skin in structure and wound healing mechanism. Pigs are regarded as the best model with regards to similarity to human skin; however, these studies are expensive, time-consuming, and only small numbers of biologic replicates can be obtained. In addition, local-regional effects of treating wounds that are closely adjacent to one-another with different treatments make assessment of treatment effectiveness difficult in pig models. Therefore, here, a novel nude mouse model of xenografted porcine hypertrophic scar (HTS) cells was developed. This model system was developed to test if supplying hypo-pigmented cells with exogenous alpha melanocyte stimulating hormone (α-MSH) will reverse pigment loss .
METHODS
Dyschromic HTSs were created in red Duroc pigs. Epidermal scar cells (keratinocytes and melanocytes) were derived from regions of hyper-, hypo-, or normally pigmented scar or skin and were cryopreserved. Dermal fibroblasts (DFs) were isolated separately. Excisional wounds were created on nude mice and a grafting dome was placed. DFs were seeded on day 0 and formed a dermis. On day 3, epidermal cells were seeded onto the dermis. The grafting dome was removed on day 7 and hypo-pigmented xenografts were treated with synthetic α-MSH delivered with microneedling. On day 10, the xenografts were excised and saved. Sections were stained using hematoxylin and eosin hematoxylin and eosin (H&E) to assess xenograft structure. RNA was isolated and quantitative real-time polymerase chain reaction (qRT-PCR) was performed for melanogenesis-related genes , , and .
RESULTS
The seeding of HTSDFs formed a dermis that is similar in structure and cellularity to HTS dermis from the porcine model. When hyper-, hypo-, and normally-pigmented epidermal cells were seeded, a fully stratified epithelium was formed by day 14. H&E staining and measurement of the epidermis showed the average thickness to be 0.11 ± 0.07 µm 0.06 ± 0.03 µm in normal pig skin. Hypo-pigmented xenografts that were treated with synthetic α-MSH showed increases in pigmentation and had increased gene expression of , , and compared to untreated controls (TYR: 2.7 ± 1.1 0.3 ± 1.1; TYRP1: 2.6 ± 0.6 0.3 ± 0.7; DCT 0.7 ± 0.9 0.3 ± 1-fold change from control; n = 3).
CONCLUSIONS
The developed nude mouse skin xenograft model can be used to study treatments for the skin. The cells that can be xenografted can be derived from patient samples or from pig samples and form a robust dual-skin layer containing epidermis and dermis that is responsive to treatment. Specifically, we found that hypo-pigmented regions of scar can be stimulated to make melanin by synthetic α-MSH .
Topics: Animals; Mice, Nude; Cicatrix, Hypertrophic; Mice; Disease Models, Animal; Swine; alpha-MSH; Humans; Skin; Fibroblasts; Melanocytes; Keratinocytes; Transplantation, Heterologous; Wound Healing; Skin Pigmentation
PubMed: 38940034
DOI: 10.31083/j.fbl2906230 -
Frontiers in Bioscience (Landmark... May 2024Phosphine resistance in challenges grain storage. This study investigates the impact of cytochrome P450 (CYP) enzymes and CYP346 family genes on phosphine resistance in...
BACKGROUND
Phosphine resistance in challenges grain storage. This study investigates the impact of cytochrome P450 (CYP) enzymes and CYP346 family genes on phosphine resistance in Indian Tribolium castaneum populations.
METHODS
Seven field populations of were compared with Lab- susceptible population for their resistance to phosphine. The levels of cytochrome P450 enzyme and expression of certain CYP346 family genes were tracked in these populations.
RESULTS
The highly resistant Patiala population showed significantly increased CYP450 activity (11.26 ± 0.14 nmol/min/mg protein, 7.41-fold higher) compared to the lab-susceptible population (1.52 ± 0.09 nmol/min/mg protein) when assayed using 8 mM p-nitroanisole as the substrate. The mRNA expression was measured relative to the standard gene and revealed significant upregulation of and in highly resistant populations Moga and Patiala (: 12.09 ± 2.19 to 21.74 ± 3.82; : 59.097 ± 10.265 to 50.148 ± 8.272). Patiala's exhibited an impressive 685.76-fold change, and Moga's showed a 361.893-fold change compared to lab-susceptible. Linear regression confirmed robust fits for each gene (R2: 0.693 to 0.756). Principal component analysis (PCA) demonstrated a strong positive correlation between genes expression; and cytochrome P450 activity. Patiala, Moga, and Hapur populations showed conformity, associating higher resistance with increased P450 activity and CYP346 gene expression. Cluster analysis highlighted a potential correlation between , , and and P450 activity, with Patiala and Moga clustering together.
CONCLUSIONS
Variability in and in strong resistance populations may contribute to adaptation and resistance mechanisms. The study provides insights into specific CYP346 family genes associated with phosphine resistance, emphasizing the intricate interaction between CYP450 detoxifying enzymes, CYP346 family genes, and resistance mechanisms. The upregulation of genes suggests a survival advantage for against phosphine, diminishing phosphine's efficacy as a pest control measure.
Topics: Tribolium; Cytochrome P-450 Enzyme System; Insecticide Resistance; Phosphines; Insecticides; India; Animals
PubMed: 38940033
DOI: 10.31083/j.fbl2906203 -
Frontiers in Bioscience (Landmark... Jun 2024Rheumatic heart disease (RHD) is caused by inflammatory cells mistakenly attacking the heart valve due to Group A Streptococcus (GAS) infection, but it is still unclear...
BACKGROUND
Rheumatic heart disease (RHD) is caused by inflammatory cells mistakenly attacking the heart valve due to Group A Streptococcus (GAS) infection, but it is still unclear which cells or genes are involved in the process of inflammatory cells infiltrating the valve. Inflammatory infiltration into the target tissue requires an increase in the expression of phosphorylated vascular endothelial-cadherin (p-VE-cad), p-VE-cad can increase the endothelial permeability and promote the migration of inflammatory cells across the endothelium. P-VE-cad is potentially regulated by RAS-related C3 botulinum substrate 1 (RAC1), together with phosphorylated proline-rich tyrosine kinase 2 (p-PYK2). While RAC1/p-PYK2/p-VE-cad is triggered by the activation of vascular cell adhesion molecule-1 (VCAM-1). VCAM-1 is related to M1 macrophages adhering to the endothelium via very late antigen 4 (VLA4). Inflammatory infiltration into the valve is extremely important in the early pathogenesis of RHD. However, there is no relevant research on whether M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad is involved in RHD; therefore, what we explored in this study was whether M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad is involved.
METHODS
We established a rat model of RHD and a cell model of M1 macrophage and endothelial cell cocultivation. Subsequently, we measured the degree of inflammatory cell infiltration, the levels of IL-6/IL-17, the degree of fibrosis (COL3/1), and the expression levels of fibrosis markers (FSP1, COL1A1 and COL3A1) in the heart valves of RHD rats. Additionally, we detected the expression of M1/M2 macrophage biomarkers in rat model and cell model, as well as the expression of M1/VLA4/VCAM-1/RAC1/p-PYK2/p-VE-cad. We also tested the changes in endothelial permeability after coculturing M1 macrophages and endothelial cells.
RESULTS
Compared to those in the control group, the levels of inflammatory cell infiltration and fibrotic factors in the heart valves of RHD rats were significantly higher; the expression of M1 macrophage biomarkers (iNOS, CD86 and TNF-α) in RHD rats was significantly higher; and significantly higher than the expression of M2 macrophage biomarkers (Arg1 and TGF-β). And the expression levels of VLA4/VCAM-1 and RAC1/p-PYK2/p-VE-cad in the hearts of RHD rats were significantly higher. At the cellular level, after coculturing M1 macrophages with endothelial cells, the expression levels of VLA4/VCAM-1 and RAC1/p-PYK2/p-VE-cad were significantly higher, and the permeability of the endothelium was significantly greater due to cocultivation with M1 macrophages.
CONCLUSIONS
All the results suggested that M1 macrophages and the VLA4/VCAM-1 pathway are potentially involved in the process of inflammatory infiltration in RHD.
Topics: Animals; Rheumatic Heart Disease; Vascular Cell Adhesion Molecule-1; Macrophages; Rats; Integrin alpha4beta1; Male; Heart Valves; Signal Transduction; Rats, Sprague-Dawley; rac1 GTP-Binding Protein; Disease Models, Animal; Humans
PubMed: 38940032
DOI: 10.31083/j.fbl2906219 -
Frontiers in Bioscience (Landmark... Jun 2024This study investigated the impact of salvianolic acids, derived from Danshen, on melanoma cell growth. Specifically, we assessed the ability of salvianolic acid A (Sal...
BACKGROUND
This study investigated the impact of salvianolic acids, derived from Danshen, on melanoma cell growth. Specifically, we assessed the ability of salvianolic acid A (Sal A) to modulate melanoma cell proliferation.
METHODS
We used human melanoma A2058 and A375 cell lines to investigate the effects of Sal A on cell proliferation and death by measuring bromodeoxyuridine incorporation and lactate dehydrogenase release. We assessed cell viability and cycle progression using water soluble tetrazolium salt-1 (WST-1) mitochondrial staining and propidium iodide. Additionally, we used a phospho-kinase array to investigate intracellular kinase phosphorylation, specifically measuring the influence of Sal A on checkpoint kinase-2 (Chk-2) via western blot analysis.
RESULTS
Sal A inhibited the growth of A2058 and A375 cells dose-responsively and induced cell cycle arrest at the G2/M phase. Notably, Sal A selectively induces Chk-2 phosphorylation without affecting Chk-1, thereby degrading Chk-2-regulated genes and . However, Sal A does not affect the Chk1-Cdc25C pathway.
CONCLUSIONS
Salvianolic acids, especially Sal A, effectively hinder melanoma cell growth by inducing Chk-2 phosphorylation and disrupting G2/M checkpoint regulation.
Topics: Humans; Checkpoint Kinase 2; cdc25 Phosphatases; Melanoma; Cell Line, Tumor; Cell Proliferation; Lactates; Caffeic Acids; Signal Transduction; Phosphorylation; Cell Survival
PubMed: 38940031
DOI: 10.31083/j.fbl2906213 -
Frontiers in Bioscience (Landmark... Jun 2024Apricot kernels containing amygdalin (AMG) as the major cyanogenic glycoside are potentially useful as a complementary therapy for the management of several ailments...
BACKGROUND
Apricot kernels containing amygdalin (AMG) as the major cyanogenic glycoside are potentially useful as a complementary therapy for the management of several ailments including cancer. Nevertheless, little is known regarding the toxic and therapeutic doses of AMG, particularly in terms of male reproduction. Hence, this study evaluates selected qualitative characteristics of rabbit testicular tissue following administration of AMG or apricot kernels for 28 days.
METHODS
The rabbits were randomly divided into five groups (Control, P1, P2, P3, P4). The Control received no AMG/apricot kernels while the experimental groups P1 and P2 received a daily intramuscular injection of amygdalin at a dose of 0.6 and 3.0 mg/kg of body weight (b.w.) for 28 days, respectively. P3 and P4 received a daily dose of 60 and 300 mg/kg b.w. of crushed apricot kernels mixed with feed for 28 days, respectively. Changes to the testicular structure were quantified morphometrically, while tissue lysates were subjected to the evaluation of reactive oxygen species (ROS) production, total antioxidant capacity, activities of antioxidant enzymes, and glutathione concentration. The extent of damage to the proteins and lipids was quantified as well. Levels of selected cytokines were determined by the enzyme-linked immunosorbent assay while a luminometric approach was used to assess the activity of caspases.
RESULTS
Rabbits treated with 3.0 mg/kg b.w. AMG presented a significantly increased protein oxidation ( = 0.0118) accompanied by a depletion of superoxide dismutase ( = 0.0464), catalase ( = 0.0317), and glutathione peroxidase ( = 0.0002). Significantly increased levels of interleukin-1 beta ( = 0.0012), tumor necrosis factors alpha ( = 0.0159), caspase-3/7 ( = 0.0014), and caspase-9 ( = 0.0243) were also recorded in the experimental group P2 when compared to the Control. No effects were observed in the rabbits treated with apricot kernels at the oxidative, inflammatory, and histopathological levels.
CONCLUSIONS
Apricot kernels did not induce toxicity in the testicular tissues of male rabbits, unlike pure AMG, which had a negative effect on male reproductive structures carried out through oxidative, inflammatory, and pro-apoptotic mechanisms.
Topics: Animals; Male; Rabbits; Testis; Amygdalin; Prunus armeniaca; Oxidative Stress; Reactive Oxygen Species; Antioxidants; Inflammation
PubMed: 38940029
DOI: 10.31083/j.fbl2906235 -
Frontiers in Bioscience (Landmark... May 2024Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant...
BACKGROUND
Osteosarcoma (OS) is a primary malignant bone tumor in the pediatric and adolescent populations. Long non-coding RNAs (LncRNAs), such as plasma-cytoma variant translocation 1 (PVT1), have emerged as significant regulators of OS metastasis. Recent studies have indicated that activation of signal transducer and activator of transcription 3 (STAT3) signaling, which might be controlled by PVT1, inhibits ferroptosis to promote the malignant progression of cancer. Therefore, the present study aimed to determine the role of PVT1 in OS pathogenesis and investigate whether PVT1 affects OS progression by regulating STAT3/GPX4 pathway-mediated ferroptosis.
METHODS
The human OS cell line MG63 were transfected with sh-PVT1 plasmid to inhibit PVT1 expression, with or without co-transfection with a STAT3 overexpression plasmid. The expression of PVT1 was determined by real-time quantitative polymerase chain reaction (RT-qPCR). The proliferation, migration, invasion, and apoptosis of MG63 cells were determined using the cell counting kit-8 (CCK8), Transwell assay, and flow cytometry. The levels of malondialdehyde (MDA), Fe2+, and glutathione (GSH) were determined by ELISA kits, whereas reactive oxygen species (ROS) level was determined by immunofluorescence. The protein expression levels of STAT3, p-STAT3, and glutathione peroxidase 4 (GPX4) were detected by western blot (WB).
RESULTS
PVT1 expression was significantly increased in MG63 cells. When knocking down PVT1 with sh-PVT1 plasmid, the proliferation, migration, and invasion of MG63 cells were markedly inhibited, while the rate of apoptosis was upregulated. Further investigation revealed that MG63 cells with PVT1 knockdown exhibited elevated levels of MDA, Fe2+, and ROS. In addition, the inhibition of PVT1 expression resulted in decreased levels of GSH and inhibited expression of p-STAT3 and GPX4. When sh-PVT1 was co-transfected with STAT3 overexpression plasmid in MG63 cells, the increased levels of MDA, Fe2+, and ROS were downregulated, and the decreased expressions of GSH, p-STAT3, and GPX4 were upregulated.
CONCLUSION
PVT1 promotes OS metastasis by activating the STAT3/GPX4 pathway to inhibit ferroptosis. Targeting PVT1 might be a novel therapeutic strategy for OS treatment.
Topics: Humans; Osteosarcoma; RNA, Long Noncoding; Ferroptosis; STAT3 Transcription Factor; Cell Line, Tumor; Bone Neoplasms; Phospholipid Hydroperoxide Glutathione Peroxidase; Cell Proliferation; Reactive Oxygen Species; Signal Transduction; Cell Movement; Disease Progression; Apoptosis; Gene Expression Regulation, Neoplastic
PubMed: 38940027
DOI: 10.31083/j.fbl2906207 -
Frontiers in Bioscience (Landmark... Jun 2024The senescence marker protein 30 (SMP30) is a calcium-binding protein whose expression decreases with age, and is closely associated with hepatocellular carcinoma (HCC)...
BACKGROUND
The senescence marker protein 30 (SMP30) is a calcium-binding protein whose expression decreases with age, and is closely associated with hepatocellular carcinoma (HCC) development. The primary goal of this study was to examine the mechanistic effect of SMP30 on HCC migration and invasion.
METHODS
Bioinformatic and immunohistochemical approaches were used to examine the expression of SMP30 in HCC tissues and its relationship to patient survival. We investigated the effects of SMP30 expression on HCC cell proliferation, migration, invasion, and cell cycle dynamics. cDNA microarray technology was used to determine the gene expression profile of SK-Hep-1 cells following recombinant SMP30 overexpression to identify genes downstream of SMP30 that regulate HCC cell migration and invasion. We identified SMP30 interacting proteins by affinity purification-mass spectrometry (AP-MS) and co-immunoprecipitation/western blotting (COIP-WB).
RESULTS
SMP30 expression was lower in HCC tissues compared with normal liver tissues, and its expression positively correlated with overall survival in HCC patients. Additionally, SMP30 overexpression effectively blocked the migratory and invasive properties of SK-Hep-1 cells, but did not affect either proliferation rates or cell cycle. cDNA microarray results confirmed that many of the differentially expressed genes identified are involved in the process of epithelial-mesenchymal transition (EMT). AP-MS and COIP-WB experiments confirmed that Rho-associated protein kinase 1 (ROCK1) interacts with SMP30 in SK-Hep-1 cells, and ROCK1 is known to intimately regulate the EMT process.
CONCLUSION
SMP30 inhibits HCC metastasis by influencing the expression of EMT-related proteins after interacting with ROCK1.
Topics: Humans; rho-Associated Kinases; Epithelial-Mesenchymal Transition; Carcinoma, Hepatocellular; Liver Neoplasms; Calcium-Binding Proteins; Neoplasm Invasiveness; Cell Line, Tumor; Cell Movement; Cell Proliferation; Intracellular Signaling Peptides and Proteins; Male; Female; Gene Expression Regulation, Neoplastic
PubMed: 38940025
DOI: 10.31083/j.fbl2906214 -
Frontiers in Bioscience (Landmark... Jun 2024Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved...
BACKGROUND
Nonalcoholic fatty liver disease (NAFLD) is a prevalent condition characterized by hepatic fat accumulation, often progressing to severe liver injury, for which approved treatments are currently lacking. This study explores the potential therapeutic impact of alpha-lipoic acid (ALA), a natural compound crucial in lipid metabolism, on NAFLD using an model.
METHODS
HepG2 cells were treated with a palmitic acid:oleic acid (PA:OA) mixture, representing a cellular model of steatosis. Subsequent treatment with ALA at concentrations of 1 µM and 5 µM aimed to evaluate its effects on lipid content and metabolism. Real-time polymerase chain reaction (PCR), BODIPY staining, cytofluorimetric analysis, and lipidomics were used to assess gene expression, lipid droplet accumulation, and fatty acid profiles.
RESULTS
Our results showed that ALA significantly reduced lipid droplets in PA:OA-treated HepG2 cells, with a concentration-dependent effect. Analysis of fatty acid profiles demonstrated a decrease in palmitic acid levels with ALA treatment, while oleic acid reduction was observed only at the higher concentration. Moreover, ALA modulated the expression of genes involved in cholesterol biosynthesis and low-density lipoprotein (LDL) metabolism, indicating a potential role in lipid homeostasis. Further insights into molecular mechanisms revealed that ALA modulated peroxisome proliferator activated receptors (PPARs), specifically PPAR-alpha and PPAR-gamma, involved in fatty acid metabolism and insulin sensitivity. Finally, ALA counteracted the overexpression of thermogenic genes induced by exogenous fatty acids, suggesting a regulatory role in energy dissipation pathways.
CONCLUSION
In conclusion, this study highlights ALA as a therapeutic agent in mitigating lipid accumulation and dysregulation in NAFLD.
Topics: Humans; Thioctic Acid; Hep G2 Cells; Lipid Metabolism; Non-alcoholic Fatty Liver Disease; Oleic Acid; Palmitic Acid; Gene Expression Regulation; Fatty Acids; PPAR gamma; Lipid Droplets; PPAR alpha; Uncoupling Protein 2
PubMed: 38940024
DOI: 10.31083/j.fbl2906209