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Journal of Phycology Jun 2024The northward shift of Pyropia yezoensis aquaculture required the breeding of germplasms with tolerance to the oxidative stress due to the high light conditions of the...
The northward shift of Pyropia yezoensis aquaculture required the breeding of germplasms with tolerance to the oxidative stress due to the high light conditions of the North Yellow Sea area. The MPV17/PMP22 family proteins were identified as a molecule related to reactive oxygen species (ROS) metabolism. Here, one of the MPV17 homolog genes designated as PyM-LP2 was selected for functional identification by introducing the encoding sequence region/reverse complementary fragment into the Py. yezoensis genome. Although the photosynthetic activity, the respiratory rate, and the ROS level in wild type (WT) and different gene-transformed algal strains showed similar levels under normal conditions, the overexpression (OE) strain exhibited higher values of photosynthesis, respiration, and reducing equivalents pool size but lower intracellular ROS production under stress conditions compared with the WT. Conversely, all the above parameters showed opposite variation trends in RNAi strain as those in the OE strain. This implied that the PyM-LP2 protein was involved in the mitigation of the oxidative stress. Sequence analysis revealed that this PyM-LP2 protein was assorted to peroxisomes and might serve as a poring channel for transferring malate (Mal) to peroxisomes. By overexpressing PyM-LP2, the transfer of Mal from chloroplasts to peroxisomes was enhanced under stress conditions, which promoted photorespiration and ultimately alleviated excessive reduction of the photosynthetic electron chain. This research lays the groundwork for the breeding of algae with enhanced resistance to oxidative stresses.
PubMed: 38924097
DOI: 10.1111/jpy.13474 -
PloS One 2024Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam is a shrubby plant of the Asteraceae family that has medicinal benefits for the pharmaceutical and cosmetic...
Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam leaf extract prevents assault of streptozotocin on liver cells via inhibition of oxidative stress and activation of the NrF2/Keap1, PPARγ, and PTP1B signaling pathways.
BACKGROUND
Spilanthes filicaulis (Schumach. & Thonn.) C. D Adam is a shrubby plant of the Asteraceae family that has medicinal benefits for the pharmaceutical and cosmetic industries.
PURPOSE
The purpose of this study was to assess the effectiveness of Spilanthes filicaulis leaf extract in a streptozotocin (STZ)-induced rat model and the associated signaling pathways.
METHODS
A sample of 25 male Wistar rats was randomly assigned to groups I, II, III, IV, and V. Each group included five animals, i.e., control rats, diabetic control rats, diabetic rats treated with metformin, and diabetic rats treated with 150 mg/kg/bw and 300 mg/kg/bw of the methanolic extract of S. filicaulis leaves (MESFL). Treatment was administered for 15 successive days via oral gavage. After 15 days, the rats were evaluated for fasting blood glucose (FBG), glycated hemoglobin (HbA1c), alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), triglyceride (TG), total cholesterol (TC), low-density lipoprotein (LDL), high-density lipoprotein (HDL), reduced glutathione (GSH), glutathione-S-transferase (GST), superoxide dismutase (SOD), catalase (CAT), lipid peroxidation (MDA), hexokinase, and glucose-6-phosphatase activities. Gene expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2), peroxisome proliferator-activated receptor gamma (PPAR-γ), kelch-like ECH-associated protein 1 (Keap1), protein tyrosine phosphatase 1B (PTP1B) and the antiapoptotic protein caspase-3 were examined.
RESULTS
MESFL was administered to diabetic rats, and changes in body weight, fasting blood glucose (FBG) and HbA1c were restored. Furthermore, in diabetic rats, S. filicaulis significantly reduced the levels of triglycerides (TGs), total cholesterol (TC), low-density lipoprotein (LDL), and very low-density lipoprotein (VLDL) and significantly increased HDL. S. filicaulis improved ALT, AST, and ALP enzyme activity in diabetic rats. MDA levels decreased considerably with increasing activity of antioxidant enzymes, such as GST, SOD, CAT and GSH, in diabetic liver rats treated with S. filicaulis. Diabetic rats treated with MESFL and metformin exhibited upregulated mRNA expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and peroxisome proliferator-activated receptor gamma (PPAR-γ). Kelch-like ECH-associated protein 1 (Keap1) and protein tyrosine phosphatase 1B (PTP1B) mRNA expression in the liver was downregulated in diabetic rats treated with MESFL and metformin. In addition, MESFL downregulated the mRNA expression of caspase-3 in diabetic rats.
CONCLUSION
It can be concluded from the data presented in this study that MESFL exerts a protective effect on diabetic rats due to its antidiabetic, antioxidant, antihyperlipidemic and antiapoptotic effects and may be considered a treatment for T2DM.
Topics: Animals; NF-E2-Related Factor 2; Male; Plant Extracts; Kelch-Like ECH-Associated Protein 1; Oxidative Stress; Plant Leaves; Signal Transduction; Rats; Rats, Wistar; Diabetes Mellitus, Experimental; PPAR gamma; Liver; Protein Tyrosine Phosphatase, Non-Receptor Type 1; Asteraceae; Streptozocin; Hypoglycemic Agents
PubMed: 38924022
DOI: 10.1371/journal.pone.0306039 -
Cancer Medicine Jun 2024A neurotrophic tropomyosin receptor kinase (NTRK)-tyrosine kinase inhibitor (TKI) has shown dramatic efficacy against malignant tumors harboring an NTRK fusion gene....
INTRODUCTION
A neurotrophic tropomyosin receptor kinase (NTRK)-tyrosine kinase inhibitor (TKI) has shown dramatic efficacy against malignant tumors harboring an NTRK fusion gene. However, almost all tumors eventually acquire resistance to NTRK-TKIs.
METHOD
To investigate the mechanism of resistance to NTRK-TKIs, we established cells resistant to three types of NTRK-TKIs (larotrectinib, entrectinib, and selitrectinib) using KM12 colon cancer cells with a TPM3-NTRK1 rearrangement.
RESULT
Overexpression of 3-hydroxy-3-methylglutaryl-CoA synthase 2 (HMGCS2) was observed in three resistant cells (KM12-LR, KM12-ER, and KM12-SR) by microarray analysis. Lower expression of sterol regulatory element-binding protein 2 (SREBP2) and peroxisome proliferator activated receptor α (PPARα) was found in two cells (KM12-ER and KM12-SR) in which HMGCS2 was overexpressed compared to the parental KM12 and KM12-LR cells. In resistant cells, knockdown of HMGCS2 using small interfering RNA improved the sensitivity to NTRK-TKI. Further treatment with mevalonolactone after HMGCS2 knockdown reintroduced the NTRK-TKI resistance. In addition, simvastatin and silibinin had a synergistic effect with NTRK-TKIs in resistant cells, and delayed tolerance was observed after sustained exposure to clinical concentrations of NTRK-TKI and simvastatin in KM12 cells. In xenograft mouse models, combination treatment with entrectinib and simvastatin reduced resistant tumor growth compared with entrectinib alone.
CONCLUSION
These results suggest that HMGCS2 overexpression induces resistance to NTRK-TKIs via the mevalonate pathway in colon cancer cells. Statin inhibition of the mevalonate pathway may be useful for overcoming this mechanistic resistance.
Topics: Humans; Animals; Drug Resistance, Neoplasm; Mice; Cell Line, Tumor; Protein Kinase Inhibitors; Mevalonic Acid; Xenograft Model Antitumor Assays; Colonic Neoplasms; Receptor, trkA; Hydroxymethylglutaryl-CoA Synthase; Benzamides; Pyrimidines; Pyrazoles; Indazoles
PubMed: 38923428
DOI: 10.1002/cam4.7393 -
Chemistry & Biodiversity Jun 2024Myricetin (1), quercetin (2), kaempferol (3) and kaempferide (4) were flavonoids with phenolic hydroxyl groups. The antioxidant and pharmacological mechanisms of them...
Myricetin (1), quercetin (2), kaempferol (3) and kaempferide (4) were flavonoids with phenolic hydroxyl groups. The antioxidant and pharmacological mechanisms of them were investigated in detail. The lowest hydroxyl dissociation enthalpies of 1, 2, 3 and 4 were calculated by DFT, respectively. The hydroxyl dissociation enthalpies of the four flavonoids at the O2 site are the highest. By analyzing the intramolecular hydrogen bonds and HOMO-LUMO orbitals of the four flavonoids, the reasons for their divergence of hydroxyl dissociation enthalpies and antioxidant mechanisms were further investigated. The UV-vis and IR spectra of four flavonoids were compared. The interactions about electrostatic attraction, p-π conjugation and hydrogen bond combined the flavonoid with the target protein closely. The root mean square deviation of peroxisome proliferator-activated receptor γ combined with 1, 2 and 3 increased, while that of PPARγ combined with 4 decreased.
PubMed: 38923373
DOI: 10.1002/cbdv.202400752 -
The Journal of Dermatology Jun 2024Peroxisomal acyl-CoA oxidase 1 (ACOX1), is a peroxisomal enzyme that catalyzes β-oxidation of very-long-chain fatty acids (VLCFA). The gain-of-function variant...
Peroxisomal acyl-CoA oxidase 1 (ACOX1), is a peroxisomal enzyme that catalyzes β-oxidation of very-long-chain fatty acids (VLCFA). The gain-of-function variant p.Asn237Ser in ACOX1 has been shown to cause Mitchell syndrome (MITCH), a neurodegenerative disorder characterized by episodic demyelination, hearing loss, and polyneuropathy, through the overproduction of hydrogen peroxide. Only eight cases of MITCH have been reported. While all these patients experienced cutaneous abnormalities, detailed skin features and potential treatment have not been documented. Herein, we report two MITCH patients who harbored a de novo heterozygous variant p.Asn237Ser in ACOX1 and experienced progressive ichthyosiform erythroderma. Skin histopathology revealed hyperkeratosis and parakeratosis with focal hypogranulosis as well as dyskeratotic keratinocytes. Lipid accumulation in the epidermis was observed using Oil Red O staining. Both patients exhibited a remarkable response to treatment with the topical antioxidant N-acetylcysteine (NAC), with Patient 1 achieving complete recovery after 3 months of consistent treatment. This study provides the first comprehensive description of the clinicopathological characteristics and effective treatment of skin lesions in MITCH patients. The successful treatment with topical NAC suggests excessive reactive oxygen species might play a significant role in the pathogenesis of skin lesions in MITCH.
PubMed: 38923010
DOI: 10.1111/1346-8138.17346 -
Cells Jun 2024Cancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to...
Cancer is one of the most important problems of modern societies. Recently, studies have reported the anticancer properties of rosiglitazone related to its ability to bind peroxisome proliferator receptor γ (PPARγ), which has various effects on cancer and can inhibit cell proliferation. In this study, we investigated the effect of new 4-thiazolidinone (4-TZD) hybrids Les-4369 and Les-3467 and their effect on reactive oxygen species (ROS) production, metabolic activity, lactate dehydrogenase (LDH) release, caspase-3 activity, and gene and protein expression in human foreskin fibroblast (BJ) cells and lung adenocarcinoma (A549) cells. The ROS production and caspase-3 activity were mainly increased in the micromolar concentrations of the studied compounds in both cell lines. Les-3467 and Les-4369 increased the mRNA expression of , (tumor protein P53), and (ATM serine/threonine kinase) in the BJ cells, while the mRNA expression of these genes (except ) was mainly decreased in the A549 cells treated with both of the tested compounds. Our results indicate a decrease in the protein expression of AhR, PPARγ, and PARP-1 in the BJ cells exposed to 1 µM Les-3467 and Les-4369. In the A549 cells, the protein expression of AhR, PPARγ, and PARP-1 increased in the treatment with 1 µM Les-3467 and Les-4369. We have also shown the PPARγ modulatory properties of Les-3467 and Les-4369. However, both compounds prove weak anticancer properties evidenced by their action at high concentrations and non-selective effects against BJ and A549 cells.
Topics: Humans; A549 Cells; PPAR gamma; Reactive Oxygen Species; Pyrazoles; Thiazolidines; Indoles; Caspase 3; Tumor Suppressor Protein p53; Cell Proliferation; Antineoplastic Agents; Ataxia Telangiectasia Mutated Proteins; Apoptosis; Fibroblasts
PubMed: 38920636
DOI: 10.3390/cells13121007 -
BMC Plant Biology Jun 2024Cowpea wilt is a harmful disease caused by Fusarium oxysporum, leading to substantial losses in cowpea production. Melatonin reportedly regulates plant immunity to...
BACKGROUND
Cowpea wilt is a harmful disease caused by Fusarium oxysporum, leading to substantial losses in cowpea production. Melatonin reportedly regulates plant immunity to pathogens; however the specific regulatory mechanism underlying the protective effect of melatonin pretreated of cowpea against Fusarium oxysporum remains known. Accordingly, the study sought to evaluate changes in the physiological and biochemical indices of cowpea following melatonin treated to facilitate Fusarium oxysporum resistance and elucidate the associated molecular mechanism using a weighted gene coexpression network.
RESULTS
Treatment with 100 µM melatonin was effective in increasing cowpea resistance to Fusarium oxysporum. Glutathione peroxidase (GSH-PX), catalase (CAT), and salicylic acid (SA) levels were significantly upregulated, and hydrogen peroxide (HO) levels were significantly downregulated in melatonin treated samples in roots. Weighted gene coexpression network analysis of melatonin- and Fusarium oxysporum-treated samples identified six expression modules comprising 2266 genes; the number of genes per module ranged from 9 to 895. In particular, 17 redox genes and 32 transcription factors within the blue module formed a complex interconnected expression network. KEGG analysis revealed that the associated pathways were enriched in secondary metabolism, peroxisomes, phenylalanine metabolism, flavonoids, and flavonol biosynthesis. More specifically, genes involved in lignin synthesis, catalase, superoxide dismutase, and peroxidase were upregulated. Additionally, exogenous melatonin induced activation of transcription factors, such as WRKY and MYB.
CONCLUSIONS
The study elucidated changes in the expression of genes associated with the response of cowpea to Fusarium oxysporum under melatonin treated. Specifically, multiple defence mechanisms were initiated to improve cowpea resistance to Fusarium oxysporum.
Topics: Plant Diseases; Melatonin; Disease Resistance; Fusarium; Vigna; Gene Regulatory Networks; Gene Expression Regulation, Plant; Salicylic Acid
PubMed: 38918732
DOI: 10.1186/s12870-024-05289-w -
Translational Oncology Jun 2024One of the main causes of death on the globe is cancer. Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors, including PPARα, PPARδ and... (Review)
Review
One of the main causes of death on the globe is cancer. Peroxisome-proliferator-activated receptors (PPARs) are nuclear hormone receptors, including PPARα, PPARδ and PPARγ, which are important in regulating cancer cell proliferation, survival, apoptosis, and tumor growth. Activation of PPARs by endogenous or synthetic compounds regulates tumor progression in various tissues. Although each PPAR isotype suppresses or promotes tumor development depending on the specific tissues or ligands, the mechanism is still unclear. PPARs are receiving interest as possible therapeutic targets for a number of disorders. Numerous clinical studies are being conducted on PPARs as possible therapeutic targets for cancer. Therefore, this review will focus on the existing and future uses of PPARs agonists and antagonists in treating malignancies. PubMed, Science Direct, and Scopus databases were searched regarding the effect of PPARs on various types of cancers until the end of May 2023. The results of the review articles showed the therapeutic influence of PPARs on a wide range of cancer on in vitro, in vivo and clinical studies. However, further experimental and clinical studies are needed to be conducted on the influence of PPARs on various cancers.
PubMed: 38917593
DOI: 10.1016/j.tranon.2024.102039 -
Experimental Eye Research Jun 2024We aimed to determine the role of cathepsin S (CTSS) in modulating oxidative stress-induced immune and inflammatory reactions and angiogenesis in age-related macular...
We aimed to determine the role of cathepsin S (CTSS) in modulating oxidative stress-induced immune and inflammatory reactions and angiogenesis in age-related macular degeneration. Human retinal pigment epithelium cells line ARPE-19 (immature) were maintained and treated with HO. The expression of CTSS, inflammatory cytokines, and complement factors induced by oxidative stress was compared between cells incubated without (control) and with CTSS knockdown (using small interfering ribonucleic acid; siRNA). To evaluate the role of CTSS in angiogenesis, we assayed tube formation using human umbilical vein endothelial cells and conditioned medium from ARPE-19 cells. We also used a mouse model of laser-induced choroidal neovascularization. CTSS levels were higher in ARPE-19 cells treated with HO than in control cells. Oxidative stress-induced CTSS resulted in significantly elevated transcription of nuclear factor kappa B-dependent inflammatory cytokines, complement factors C3a and C5a, membrane attack complex (C5b-9), and C3a and C5a receptors. siRNA-mediated knockdown of CTSS reduced the number of inflammatory signals. Furthermore, oxidative stress-induced CTSS regulated the expression of peroxisome proliferator-activated receptor γ and vascular endothelial growth factor A/ Akt serine/threonine kinase family signaling, which led to angiogenesis. Tube formation assays and mouse models of choroidal neovascularization revealed that CTSS knockdown ameliorated angiogenesis in vitro and in vivo. The present findings suggest that CTSS modulates the complement pathway, inflammatory reactions, and neovascularization, and that CTSS knockdown induces potent immunomodulatory effects. Hence, it could be a promising target for the prevention and treatment of early- and late-stage age-related macular degeneration.
PubMed: 38914301
DOI: 10.1016/j.exer.2024.109981 -
Pharmacological Reports : PR Jun 2024Metabolic dysfunction-associated fatty liver disease has been well documented as a key independent risk factor for the development of atherosclerosis. A growing body of...
BACKGROUND
Metabolic dysfunction-associated fatty liver disease has been well documented as a key independent risk factor for the development of atherosclerosis. A growing body of evidence suggests that due to its numerous favorable molecular effects, trehalose may exert beneficial effects in counteracting liver steatosis. In our previous study, we described the antiatherosclerotic and antisteatotic properties of trehalose, which we attributed to the induction of autophagy. Considering the pleiotropic activities of trehalose, our present study aimed to extend our preliminary results with the comprehensive examination of proteome-wide changes in the livers of high-fat-fed apoE-/- mice.
METHODS
Thus, we applied modern, next-generation proteomic methodology to comprehensively analyze the effects of trehalose on the alterations of liver proteins in apoE-/- mice.
RESULTS
Our proteomic analysis showed that the administration of trehalose elicited profound changes in the liver proteome of apoE-/- mice. The collected data allowed the identification and quantitation of 3 681 protein groups of which 129 were significantly regulated in the livers of trehalose-treated apoE-/- mice.
CONCLUSIONS
The presented results are the first to highlight the effects of disaccharide on the induction of proteins mainly related to the metabolism and elimination of lipids, especially by peroxisomal β-oxidation. Our study provides evidence for the pleiotropic activity of trehalose, extending our initial observations of its potential mechanisms responsible for mitigating of liver steatosis, which paves the way for new pharmacological strategies in fatty liver disease.
PubMed: 38913153
DOI: 10.1007/s43440-024-00615-3