Search Results (3,817)

Triple-negative breast cancer (TNBC) is a highly aggressive and therapeutically challenging subtype of breast cancer due to its lack of estrogen receptors, progesterone receptors, and HER2 (Human epidermal growth factor receptor 2) expression, which severely limits available treatment options. Recently, Simvastatin—a widely used HMG-CoA (3-hydroxy-3-methylglutaryl-coenzyme A) reductase inhibitor for hyperlipidemia—has garnered interest for its potential anticancer effects. This study investigates the therapeutic potential of Simvastatin in triple-negative breast cancer (TNBC). The results demonstrate that Simvastatin significantly inhibits the proliferation of TNBC cells, particularly MDA-MB-231, in a dose- and time-dependent manner. Mechanistically, Simvastatin primarily induces G1 phase cell cycle arrest to exert its antiproliferative effects, with no significant evidence of apoptosis or necrosis. These findings support the potential repositioning of Simvastatin as a therapeutic agent to suppress TNBC cell growth. Further analysis shows that Simvastatin downregulates cyclin-dependent kinase 4 (CDK4), a key regulator of the G1/S cell cycle transition and a known marker of poor prognosis in breast cancer. These findings highlight a novel, apoptosis-independent mechanism of Simvastatin’s anticancer action in TNBC. Importantly, given that many breast cancer patients also suffer from hyperlipidemia, Simvastatin offers dual therapeutic benefits—managing both lipid metabolism and tumor cell proliferation. Thus, Simvastatin holds promise as an adjunctive therapy in the treatment of TNBC and warrants further clinical investigation. Full article

Aging is a complex, universal biological process characterized by the progressive and irreversible decline of physiological functions across multiple organ systems. This deterioration is primarily driven by cumulative cellular damage arising from both intrinsic and extrinsic stressors. The free radical theory of aging, first proposed by Denham Harman in 1956, highlights the role of reactive oxygen species (ROS), byproducts of normal metabolism, in driving oxidative stress and age-related degeneration. Emerging evidence emphasizes the importance of redox imbalance in the onset of neurodegenerative diseases and aging. Among the critical cellular defenses against oxidative stress are sulfur-containing amino acids, namely cysteine (Cys) and selenocysteine (Sec). Cysteine serves as a precursor for glutathione (GSH), a central intracellular antioxidant, while selenocysteine is incorporated into key antioxidant enzymes such as glutathione peroxidases (GPx) and thioredoxin reductases (TrxR). These molecules play pivotal roles in neutralizing ROS and maintaining redox homeostasis. This review aims to provide an updated and critical overview of the role of thiol-containing amino acids, specifically cysteine and selenocysteine, in the regulation of redox homeostasis during aging. Full article

The worldwide increase in antifungal resistance, particularly in Candida sp., requires the exploration of novel therapeutic agents. Natural compounds have been a rich source of antimicrobial molecules, where peptides constitute the class of the most bioactive components. Therefore, this study looks into the target-specific binding efficacy of insect-derived antifungal peptides (n = 37) as possible alternatives to traditional antifungal treatments. Using computational methods, namely the HPEPDOCK and HDOCK platforms, molecular docking was performed to evaluate the interactions between selected key fungal targets, lanosterol 14-demethylase, or LDM (PDB ID: 5V5Z), secreted aspartic proteinase-5, or Sap-5 (PDB ID: 2QZX), N-myristoyl transferase, or NMT (PDB ID: 1NMT), and dihydrofolate reductase, or DHFR, of C. albicans. The three-dimensional peptide structure was modelled through the PEP-FOLD 3.5 tool. Further, we predicted the physicochemical properties of these peptides through the ProtParam and PEPTIDE 2.0 tools to assess their drug-likeness and potential for therapeutic applications. In silico results show that Blap-6 from Blaps rhynchopeter and Gomesin from Acanthoscurria gomesiana have the most antifungal potential against all four targeted proteins in Candida sp. Additionally, a molecular dynamics simulation study of LDM-Blap-6 was carried out at 100 nanoseconds. The overall predictions showed that both have strong binding abilities and are good candidates for drug development. In in vitro studies, Gomesin achieved complete biofilm eradication in three out of four Candida species, while Blap-6 showed moderate but consistent reduction across all species. C. tropicalis demonstrated relative resistance to complete eradication by both peptides. The present study provides evidence to support the antifungal activity of certain insect peptides, with potential to be used as alternative drugs or as a template for a new synthetic or modified peptide in pursuit of effective therapies against Candida spp. Full article

Background/Objectives: Paeonia delavayi, a high-altitude-adapted medicinal and oil-producing plant, exhibits broad elevational distribution. Understanding how environmental factors regulate its growth across altitudes is critical for optimizing cultivation and exploiting its economic potential. Methods: In this study, we conducted a comprehensive Iso-Seq and RNA-seq analysis to elucidate the transcriptional profile across diverse altitudes and three seed developmental stages. Results: Using Pacbio full-length cDNA sequencing, we identified 39,267 full-length transcripts, with 80.03% (31,426) achieving successful annotation. RNA-seq analysis uncovered 11,423 and 9565 differentially expressed genes (DEGs) in response to different altitude and developmental stages, respectively. KEGG analysis indicated that pathways linked to fatty acid metabolism were notably enriched during developmental stages. In contrast, pathways associated with amino acid and protein metabolism were significantly enriched under different altitudes. Furthermore, we identified 34 DEGs related to fatty acid biosynthesis, including genes encoding pivotal enzymes like biotin carboxylase, carboxyl transferase subunit alpha, malonyl-CoA-acyl carrier protein transacylase, 3-oxoacyl-ACP reductase, 3-hydroxyacyl-ACP dehydratase, and stearoyl-ACP desaturase enoyl-ACP reductase. Additionally, ten DEGs were pinpointed as potentially involved in high-altitude stress response. Conclusions: These findings provide insights into the molecular mechanisms of fatty acid biosynthesis and adaptation to high-altitude stress in peony seeds, providing a theoretical foundation for future breeding programs aimed at enhancing seed quality. Full article

This study analyzed the heavy metal tolerance and chromium reduction and the potential of plant growth to promote Rhizobium sp. OS-1. By genetic makeup, the Rhizobium strain is nitrogen-fixing and phosphate-solubilizing in metal-contaminated agricultural soil. Among the Rhizobium group, bacterial strain OS-1 showed a significant tolerance to heavy metals, particularly chromium (900 µg/mL), zinc (700 µg/mL), and copper. In the initial investigation, the bacteria strains were morphologically short-rod, Gram-negative, appeared as light pink colonies on media plates, and were biochemically positive for catalase reaction and the ability to ferment glucose, sucrose, and mannitol. Further, bacterial genomic DNA was isolated and amplified with the 16SrRNA gene and sequencing; the obtained 16S rRNA sequence achieved accession no. HE663761.1 from the NCBI GenBank, and it was confirmed that the strain belongs to the Rhizobium genus by phylogenetic analysis. The strain’s performance was best for high hexavalent chromium [Cr(VI)] reduction at 7–8 pH and a temperature of 30 °C, resulting in a total decrease in 96 h. Additionally, the adsorption isotherm Freundlich and Langmuir models fit best for this study, revealing a large biosorption capacity, with Cr(VI) having the highest affinity. Further bacterial chromium reduction was confirmed by an enzymatic test of nitro reductase and chromate reductase activity in bacterial extract. Further, from the metal biosorption study, an Artificial Neural Network (ANN) model was built to assess the metal reduction capability, considering the variables of pH, temperature, incubation duration, and initial metal concentration. The model attained an excellent expected accuracy (R² > 0.90). With these features, this bacterial strain is excellent for bioremediation and use for industrial purposes and agricultural sustainability in metal-contaminated agricultural fields. Full article

This study aimed to evaluate the production of xylose reductase (XR), an enzyme responsible for converting xylose into xylitol, by Candida tropicalis ATCC 750 using hemicellulosic hydrolysate from cashew apple bagasse (CABHM) as a low-cost carbon source. The effects of temperature, aeration, and fluid dynamics on XR biosynthesis were also investigated. The highest XR production (1.53 U mL⁻¹) was achieved at 30 °C, with 8.3 g·L⁻¹ of xylitol produced by the yeast under microaerobic conditions, demonstrating that aeration and fluid dynamics are important factors in this process. Cellular metabolism and enzyme production decreased at temperatures above 35 °C. The maximum enzymatic activity was observed at pH 7.0 and 50 °C. XR is a heterodimeric protein with a molecular mass of approximately 30 kDa. These results indicate that CABHM is a promising substrate for XR production by C. tropicalis, contributing to the development of enzymatic bioprocesses for xylitol production from lignocellulosic biomass. This study also demonstrates the potential of agro-industrial residues as sustainable feedstocks in biorefineries, aligning with the principles of a circular bioeconomy. Full article

Mung bean (Vigna radiate) sprouts are a popular choice among sprouted vegetables in Asia. Currently, the impact of nitrogen sources on the growth of mung bean sprouts remains poorly understood, and the underlying biological mechanisms responsible for the observed nonlinear growth patterns at different nitrogen levels have yet to be elucidated. In this research, in addition to conventional growth monitoring and quality evaluation, a comparative proteomics method was applied to investigate the molecular mechanisms of mung bean in response to 0, 0.025, 0.05, 0.075, and 0.1% urea concentrations. Our results indicated that mung bean sprout height and yield increased with rising urea concentrations but were suppressed beyond the L3 level (0.075% urea). Nitrate nitrogen and free amino acid content rose steadily with urea levels, whereas protein content, nitrate reductase activity, and nitrite levels followed a peak-then-decline trend, peaking at intermediate concentrations. Differential expression protein analysis was conducted on mung bean sprouts treated with different concentrations of urea, and more differentially expressed proteins participated in the L3 urea concentration. Analysis of common differential proteins among comparison groups showed that the mung bean sprouts enhanced their adaptability to urea stress environments by upregulating chlorophyll a-b binding protein and cationic amino acid transporter and downregulating the levels of glycosyltransferase, L-ascorbic acid, and cytochrome P450. The proteomic analysis uncovered the regulatory mechanisms governing these metabolic pathways, identifying 47 differentially expressed proteins (DEPs) involved in the biosynthesis of proteins, free amino acids, and nitrogen-related metabolites. Full article

Glutathione S-transferases (GSTs) are phase II detoxification enzymes that display several enzymatic activities, including transferase, peroxidase, reductase, and isomerase functions, as well as non-enzymatic roles (e.g., serving as binding proteins). Their complex functionality lies in the biotransformation of xenobiotics (e.g., pesticides, drugs) and certain endogenous compounds, primarily metabolites produced by phase I detoxification enzymes. Several plant-derived compounds have been shown to modulate the activity and expression levels of these enzymes. Phytochemical activators of GSTs are potentially beneficial for detoxification in cases of exposure to various toxic compounds, whereas inhibitors of GSTs could have positive effects as adjuvant treatments for cancers that express high levels of GSTs associated with drug resistance. Full article

Nitric oxide is a gaseous signalling molecule produced by plants. Slight changes in endogenous NO levels have significant biochemical and physiological consequences. We investigated the structural and functional properties of NO-responsive antiporter genes in Arabidopsis thaliana. Phylogenetic analysis of 50 antiporter genes classified them into four subgroups based on the presence of NHX and CPA domains and the evolutionary similarity of the protein sequences. Antiporters were found scattered across the five chromosomes with unique physico-chemical properties and subcellular localisation in the plasma membrane, nucleus, chloroplasts, and vacuole. Furthermore, we performed QPCR analysis of eight different antiporter genes after infiltrating the plants with 1 mM CySNO (S-nitroso-L-cysteine), a nitric oxide donor, in WT and the loss-of-function atgsnor1-3 (disruptive S-nitrosoglutathione reductase 1 activity) plants. The AT1G79400 (CHX2), AT2G38170 (RCI4), and AT5G17400 (ER-ANT1) showed a significant increase in their expression in response to CySNO infiltration. However, their expression in atgsnor1-3 plants was found to be lower than in the WT plants, indicating a significant redundancy in the response of these genes to 1 mM levels of CySNO and physiological levels of SNOs in atgsnor1-3. On the other hand, a significant reduction in the expression of AT1G16380 (CHX1), AT2G47600 (MHX1), AT3G13320 (CAX2), and AT5G11800 (KEA6) was observed in WT plants after CySNO infiltration as well as in the leaves of atgsnor1-3 plants. Our study identified three NO-responsive antiporter genes in Arabidopsis, indicating their roles in stress responsiveness and ion homeostasis that could be used for further validation of their roles in NO signalling in plants. Full article

Soil organic nitrogen (SON) positively influences crop productivity, greenhouse gas (GHG) emissions, and sustained nitrogen (N) supply. Herein, we observed the effect of different treatments; no fertilizers (CK), chemical fertilizers (nitrogen, phosphorus, and potassium (NPK)), organic manure, and NPK + OM (NPKOM). This study was performed in a randomized complete block design (RCBD) with three replications. The results indicated that NPKOM treatment significantly decreased the nitrous oxide (N₂O) emissions by 19.97% and 17.47% compared to NPK in both years. This was linked with improved soil nutrient availability, soil organic carbon, soil organic nitrogen (SON) storage (10.06% and 12.38%), SON sequestration (150% and 140%), increased soil particulate (44.11% and 44%), and mineral-associated organic N (26.98% and 26.47%) availability. Furthermore, NPKOM also enhanced nitrate reductase (NR: 130% and 112%), glutamine synthetase (GS: 93% and 88%), sucrose phosphate synthase (SPS: 79% and 98%), SSs (synthetic direction; 57% and 50%), and decreased SSs activity in the decomposition direction (18% and 21%). This, in turn, inhibited the decomposition of sucrase and enhanced starch conversion into carbohydrates, thus leading to an increase in rice yield and a decrease in N₂O emissions. All fertilizations, particularly NPKOM, significantly enhanced grain protein contents by increasing N uptake and its availability. Therefore, NPKOM is an effective practice to enhance rice productivity, and SON sequestration and mitigate the N₂O emissions and subsequent climate change. Full article

Background/Objectives: Astaxanthin, a xanthophyll carotenoid, has garnered significant interest due to its benefits with regard to dyslipidemia. This multifaceted functional food ingredient modulates several key enzymes associated with lipid regulation, including HMG-CoA reductase, CPT1, ACCβ, and acyl-CoA oxidase. It influences key antioxidant molecular pathways like the Nrf2, limiting dyslipidemia occurrence and regulating liver cholesterol uptake through the modulation of liver lipid receptors. Due to the current lack of systematic reviews and meta-analyses assessing moderate to high dosages (6–24 mg/d) of astaxanthin supplementation on lipid dysregulation, the present manuscript aims to fill this gap in the literature. Methods: Following the PRISMA guidelines, we included eight studies comprising eleven results from the PubMed, Springer Link, Science Direct, Cochrane, and Google Scholar databases. The Jamovi (Version 2.6.26, Solid) software was utilized for statistics. Our primary objective was to assess in detail the effects of astaxanthin on LDL-C, HDL-C, triglyceride, and total cholesterol levels. Results: The meta-analysis concludes positive effects of astaxanthin (6–20 mg/d) on HDL-C (0.4200; 95% CI: 0.1081 to 0.7319) and triglyceride (−0.3058; 95% CI: −0.5138 to −0.0978) levels. Unfortunately, astaxanthin (6–20 mg/d) does not appear to significantly influence LDL-C (−0.0725; 95% CI: −0.3070 to 0.1620) and total cholesterol (−0.0448; 95% CI: −0.3369 to 0.2473) levels. Regarding HDL-C, improvements were observed from 55 ± 8 mg/dL (pre-intervention) to 63 ± 8 mg/dL (post-intervention) (p < 0.01) in the 12 mg/d of astaxanthin groups. In the assessment of triglyceride levels, results show a decrease from 151 ± 26 mg/dL (pre-intervention) to 112 ± 40 mg/dL (post-intervention) (p < 0.01) for 18 mg/d astaxanthin supplementation. Conclusions: Further research is necessary to fully harness the potential of astaxanthin, which includes assessing astaxanthin in different subsets of patients, using a GWAS, and in combination with other nutraceuticals to understand the compound’s effectiveness with regard to varying health conditions, genetic and epigenetic factors, and synergistic effects with other compounds. Full article

To explore the effects of various zinc (Zn) fertilizer application methods and concentrations on foxtail millet quality and flavonoid biosynthesis, we used Zhangzagu 13 as the experimental material. The transcriptome and metabolome were used to examine variations in flavonoid biosynthesis and metabolism in foxtail millet under different Zn application methods. The results showed that different Zn application methods significantly increased the total polyphenol, carotenoid, total flavonoid, and Zn contents in the grains of foxtail millet. Under the basal soil application (S3) and foliar spray (F2) treatments, the total flavonoid content significantly increased by 45.87% and 64.40%, respectively, compared with that of CK. Basal soil Zn fertilization increased the flavonoid content of foxtail millet by up-regulating genes related to flavonoid metabolism and biosynthesis, including flavanone-3-hydroxylase, chalcone isomerase, and leucoanthocyanidin reductase. Foliar Zn application enhanced flavonoid content by up-regulating genes involved in flavonoid metabolic and biosynthetic processes and chalcone isomerase. In conclusion, using Zn fertilizer can improve the synthesis and metabolism of foxtail millet flavonoids, effectively increase the content of functional substances in grains, and realize the biofortification of foxtail millet grains. Full article

Perilla seed has long been recognized in traditional diets for its health-promoting properties, but its potential role in hair loss prevention remains underexplored. This study compared three extraction methods—maceration (MAC), screw pressing (SC), and supercritical fluid extraction (SFE)—to determine their efficiency in recovering bioactive compounds and their effects on androgenetic alopecia (AGA)-related pathways. The SFE extract contained the highest levels of polyunsaturated fatty acids and tocopherols, while MAC uniquely recovered a broader range of polyphenols. Among all extracts, SFE-derived perilla seed extract showed the most consistent biological effects, promoting proliferation of human hair follicle dermal papilla cells (HFDPCs) by 139.4 ± 1.1% at 72 h (p < 0.05). It also reduced TBARS and nitrite levels in HFDPCs to 66.75 ± 0.62% of control and 0.87 ± 0.01 μM, respectively, indicating strong antioxidant and anti-inflammatory effects. Importantly, the SFE extract significantly downregulated SRD5A1-3 and TGF-β1 expression—key genes involved in androgen-mediated hair follicle regression—outperforming finasteride, dutasteride, and minoxidil in vitro by approximately 1.10-fold, 1.25-fold, and 1.50-fold, respectively (p < 0.05). These findings suggest that perilla seed extract obtained via supercritical fluid extraction may offer potential as a natural candidate to prevent hair loss through multiple biological mechanisms. These in vitro results support its further investigation for potential application in functional food or nutraceutical development targeting scalp and hair health. Full article

Background: Peritoneal stretching from CO₂ insufflation is a primary mechanism of pain associated with laparoscopy. Cyclooxygenase-2 inhibitors are promising anti-inflammatory and analgesic agents. This study aimed to evaluate the effect of celecoxib on postoperative pain reduction and associated changes in peritoneal gene expression after laparoendoscopic single-site (LESS) surgery for benign gynecologic disease. Methods: In this randomized, double-blind, placebo-controlled pilot study, 70 patients were randomly assigned to receive either celecoxib or placebo (400 mg) 40 min before surgery. Peritoneal tissues were collected before and after CO₂ insufflation. We analyzed changes in expressions of prostaglandin I₂ synthase, prostaglandin E synthase (PTGES), PTGES3, aldo-keto reductase family 1 member C1, and 15-hydroxyprostaglandin dehydrogenase (HPGD). Numeric Rating Scale (NRS) pain scores were also compared between groups. Results: A total of 62 patients completed the study: 30 in the celecoxib group and 32 in the placebo group. The mean CO₂ exposure time was 60.4 min. In a quantitative real-time polymerase chain reaction analysis, HPGD mRNA expression significantly increased after surgery in patients exposed to CO₂ for more than 60 min. Patients treated with celecoxib showed a significantly higher rate of grade 3 expression (83.3% vs. 37.5%; p = 0.01) and a level 2 increase in HPGD expression on in situ hybridization (58.3% vs. 12.5%; p = 0.01), despite no significant difference on immunohistochemistry. Moreover, celecoxib effectively reduced NRS pain scores compared to placebo. Conclusions: In this pilot study, celecoxib appeared to reduce postoperative pain and was associated with increased HPGD mRNA expression in the peritoneal tissue of patients with prolonged CO₂ exposure during LESS surgery. These exploratory findings warrant confirmation in larger trials with functional validation of HPGD expression (ClinicalTrials.gov, NCT03391570). Full article

Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal lung disorder characterized by excessive scarring of lung tissue, predominantly affecting middle-aged and elderly populations. Oxidative stress plays a pivotal role in the pathogenesis of pulmonary fibrosis, disrupting redox homeostasis and driving fibrotic progression. Glutathione reductase (GSR), a key antioxidant enzyme, is essential for maintaining cellular glutathione (GSH) levels and mitigating oxidative damage. However, the specific involvement of GSR in IPF remains poorly understood. This study found that GSR levels were downregulated in IPF patients and mice treated with bleomycin (BLM). GSR knockdown enhanced epithelial-to-mesenchymal transition (EMT) in A549 cells and promoted the activation of MRC5 cells. Additionally, GSR depletion promoted cellular migration and senescence in both A549 and MRC5 cells. Mechanistically, silencing GSR in A549 and MRC5 cells led to a marked reduction in intracellular GSH levels, resulting in elevated reactive oxygen species (ROS) accumulation, thereby promoting the activation of the TGF-β/Smad2 signaling pathway. In conclusion, our findings demonstrate that GSR deficiency aggravates pulmonary fibrosis by impairing antioxidant defense mechanisms, promoting EMT, and activating fibroblasts through the TGF-β/Smad2 signaling. These findings suggest that GSR may be essential in reducing the fibrotic progression of IPF. Full article