Search Results (79)

Background/Objectives: Metabolic syndrome (MetS) is a multifactorial condition characterized by abdominal obesity, dyslipidemia, insulin resistance, hypertension, and chronic inflammation. As its global prevalence rises, there is increasing interest in natural, multi-targeted approaches to manage MetS. Curcuma longa Linn. (turmeric), especially its active compound curcumin, has shown therapeutic promise in preclinical studies. This systematic review and meta-analysis evaluated the effects of Curcuma longa and its derivatives on MetS-related outcomes in rodent models. Methods: A comprehensive search was conducted across six databases (PubMed, Scopus, AMED, LILACS, MDPI, and Google Scholar), yielding 47 eligible in vivo studies. Data were extracted on key metabolic, inflammatory, and oxidative stress markers and analyzed using random-effects models. Results were presented as mean differences (MD) with 95% confidence intervals (CI). Results: Meta-analysis showed that curcumin significantly reduced body weight (rats: MD = −42.10; mice: MD = −2.91), blood glucose (rats: MD = −55.59; mice: MD = −28.69), triglycerides (rats: MD = −70.17; mice: MD = −24.57), total cholesterol (rats: MD = −35.77; mice: MD = −52.61), and LDL cholesterol (rats: MD = −69.34; mice: MD = −42.93). HDL cholesterol increased significantly in rats but not in mice. Inflammatory cytokines were markedly reduced, while oxidative stress improved via decreased malondialdehyde (MDA) and elevated superoxide dismutase (SOD) and catalase (CAT) levels. Heterogeneity was moderate to high, primarily due to variations in curcumin dosage (ranging from 10 to 500 mg/kg) and treatment duration (2 to 16 weeks) across studies. Conclusions: This preclinical evidence supports Curcuma longa as a promising functional food component for preventing and managing MetS. Its multi-faceted effects warrant further clinical studies to validate its translational potential. Full article

Background/Objectives: Cancer suffers from unresolved therapeutic challenges owing to the lack of targeted therapies and heightened recurrence risk. This study aimed to investigate the new series of hydroxamate by structurally modifying the pharmacophore of vorinostat. Methods: The present work involves the synthesis of 15 differently substituted 2H-1,2,3-triazole-based hydroxamide analogs by employing triazole ring as a cap with varied linker fragments. The compounds were evaluated for their anticancer effect, especially their anti-breast cancer response. Molecular docking and molecular dynamics simulations were conducted to examine binding interactions. Results: Results indicated that among all synthesized hybrids, the molecule VI(i) inhibits the growth of MCF-7 and A-549 cells (GI₅₀ < 10 μg/mL) in an antiproliferative assay. Compound VI(i) was also tested for cytotoxic activity by employing an MTT assay against A549, MCF-7, and MDA-MB-231 cell lines, and the findings indicate its potent anticancer response, especially against MCF-7 cells with IC₅₀ of 60 µg/mL. However, it experiences minimal toxicity towards the normal cell line (HEK-293). Mechanistic studies revealed a dual-pathway activation: first, apoptosis (17.18% of early and 10.22% of late apoptotic cells by annexin V/PI analysis); second, cell cycle arrest at the S and G2/M phases. It also promotes ROS generation in a concentration-dependent manner. The HDAC–inhibitory assay, extended in silico molecular docking, and MD simulation experiments further validated its significant binding affinity towards HDAC 1 and 6 isoforms. DFT and ADMET screening further support the biological proclivity of the title compounds. The notable biological contribution of VI(i) highlights it as a potential candidate, especially against breast cancer cells. Full article

The 14-3-3 proteins play crucial roles in regulating plant growth, development, signal transduction and abiotic stress responses. However, there exists a scarcity of research on the role of 14-3-3 proteins in responding to abiotic stress in apples. In this study, we isolated the MdGRF22 gene from the apple 14-3-3 family. Through the screening of interacting proteins and genetic transformation of Arabidopsis thaliana and apple callus tissues, the function of the MdGRF22 gene under drought stress was verified. The coding sequence (CDS) of MdGRF22 consists of 786 bp and encodes for 261 amino acids. Through sequence alignment, the conserved 14-3-3 domain was identified in MdGRF22 and its homologous genes, which also share similar gene structures and conserved motifs. Subcellular localization revealed that the MdGRF22 protein was predominantly located in the cytoplasm and cell membrane. The yeast two-hybrid (Y2H) analysis demonstrated a possible interaction between MdGRF22 and MdSK. In addition, MdGRF22 transgenic plants generally exhibited lower superoxide dismutase (SOD), catalase (CAT) and peroxidase (POD) activities, higher malondialdehyde (MDA) levels and relative electrolyte leakage under drought conditions compared with wild-type (WT) plants. Our study suggests that MdGRF22 may reduce the drought resistance of transgenic A. thaliana and callus tissues by interacting with MdSK. This study provides a theoretical basis for further exploring the function of 14-3-3 family genes. Full article

This study systematically evaluates the hepatoprotective effects of different types and doses of Antrodia cinnamomea extracts (triterpenoids, polysaccharides, and ubiquinone derivatives) on liver function biomarkers, including alanine aminotransferase (ALT), aspartate aminotransferase (AST), malondialdehyde (MDA), and tumor necrosis factor-alpha (TNF-α), using a network meta-analysis (NMA) approach. Comprehensive literature searches were conducted in PubMed, Embase, Cochrane CENTRAL, and Web of Science databases to identify eligible animal studies involving standardized mouse and rat models. Interventions were categorized based on extract types and dosage levels (high, medium, low), with controls including negative groups (vehicle-treated) and positive groups (e.g., silymarin, N-acetylcysteine). A random-effects model estimated mean differences (MDs) with 95% confidence intervals (CIs), risk of bias was assessed with the SYRCLE tool, and sensitivity analyses verified robustness. The protocol has been registered in INPLASY (INPLASY202540040). The results indicated that triterpenoids, particularly at high and medium doses, were the most effective in reducing ALT (MD: −42.37, 95% CI: −54.19 to −30.54) and AST (MD: −50.18, 95% CI: −73.31 to −27.05). High-dose polysaccharides also showed notable effects, while other interventions demonstrated variable efficacy. For oxidative stress, high-dose triterpenoids showed the most pronounced reduction in MDA (MD: −19.05, 95% CI: −24.00 to −14.09), followed by medium-dose triterpenoids and all-dose polysaccharides. Regarding inflammation, high- and medium-dose triterpenoids significantly reduced TNF-α levels (high-dose MD: −88.75, 95% CI: −119.68 to −57.82; medium-dose MD: −89.27, 95% CI: −125.51 to −53.02), with overlapping confidence intervals indicating similar efficacy. High- and low-dose polysaccharides also demonstrated moderate anti-inflammatory effects. In conclusion, high-dose triterpenoids showed favorable and consistent effects across multiple biomarkers, which highlights their potential value for future liver-related therapeutic strategies. Full article

This study was conducted to investigate the effects of two mycotoxin detoxifications on laying hens. A total of 360 70-week-old Hy-Line Brown laying hens were randomly divided into 1 of the 4 dietary treatment groups, with 6 replicates per group and 15 hens per replicate. The laying hens of the four treatments were fed with a basal diet (CON), a diet with naturally low-level mycotoxin contaminated corn (the levels of AFB₁, ZEA, and DON in the corn of the CON group were 1.68 μg/kg, 42.75 μg/kg, and 585.40 μg/kg, respectively), replacing 73% of the corn in CON (MC), the MC diet with 1 g/kg modified silica-aluminate mycotoxin adsorbent (MA), and the MC diet with 1 g/kg mycotoxin degrading enzyme and bacteria complexes degradation agent (MD), respectively. Liver tissue and serum samples were extracted at the end of the trial to assess the antioxidant status and hepatic injury biomarkers. The experimental data were preliminarily interpreted in Excel and then analyzed by one-way ANOVA using SPSS, version 25 (SPSS Inc., Chicago, IL, USA). The results showed that compared to the CON, the MC group had decreased laying rate (p < 0.05), ferric reducing antioxidant potential in serum (p < 0.05), and reduced glutathione (GSH) content in the liver, and increased feed/egg ratio, serum alanine aminotransferase (ALT) activity, and malondialdehyde (MDA) content. Compared to the MC group, feed/egg ratio and serum ALT activity in the MA group and MD group decreased (p < 0.05), while serum GSH content and superoxide dismutase activity in the liver of the MA and MD groups increased. The liver glutathione peroxidase activity and the egg yolk percentage in the MA group decreased (p < 0.05) compared to the MC group. Histopathological alterations in liver tissues induced by mycotoxin included vacuolar degeneration, hepatocyte necrosis and disintegration, inflammatory cell infiltration, and enlarged hepatic sinuses. In short, both MA and MD were effective in mitigating the combined effects of low-level mycotoxins on laying hen performance, antioxidant capacity and liver damage. Full article

Kaempferia galanga L. is well known for its use in medicinal and edible homologous application. Various diseases, including those related to oxidation, are commonly treated with it. However, its antioxidant effect is still lacking systematical study. We aimed to screen the most potential antioxidant fraction of the crude ethanolic extract from K. galanga (KG) and evaluate its antioxidant activity and potential mechanism. The ethyl acetate fraction of ethanolic extract from K. galanga (KGEA) was chosen as the most potent antioxidant activity from all the fractions tested. UPLC-Q-TOF-MS/MS was used to determine 43 compounds in KGEA, and 25 potential bioactive compounds were identified by pharmacokinetic analysis. Network pharmacology revealed 174 overlapping targets of chemical and antioxidant targets, and the key targets were identified. Molecular docking and MD simulation revealed a strong binding affinity between the core compounds and their targets. In tests against DPPH and ABTS, KGEA exhibited potent radical scavenging activity. In H₂O₂-induced cells, KGEA could decrease reactive oxygen species (ROS) production; alleviate mitochondrial damage; promote the increase in antioxidant enzymes SOD, CAT, GSH-Px; and reduce the levels of MDA. Mechanistically, KGEA regulated PI3K/Akt and MAPK signaling pathways against oxidative damage. Moreover, in H₂O₂-induced zebrafish, KGEA attenuated ROS generation, cell death, lipid peroxidation, and increased SOD, CAT, GSH-Px activities; it also decreased MDA levels. The antioxidant properties of KGEA were demonstrated in vitro and in vivo, and it should be considered as an antioxidant agent for further profound study. Full article

PD-L1 (programmed cell death ligand-1) is a protein located on the surface of regulatory cells. It has an immunosuppressive role as it binds specifically to the protein programmed cell death-1 (PD-1), a checkpoint glycoprotein, present on the surface of immune cells such as T and B lymphocytes. Many tumor cells block the immune response by overexpressing PD-L1 on their surface; therefore, targeting PD-L1 represents a powerful strategy that allows tumor localization. To determine the presence of PD-L1 in cells, the use of ad hoc functionalized peptides that bind to PD-L1 can be exploited. One of them is the peptide CLP002 (Trp-His-Arg-Ser-Tyr-Tyr-Thr-Trp-Asn-Leu-Asn-Thr), which, bound to surface-enhanced Raman scattering (SERS) gold nanostructures via a suitable linker, was shown to be highly effective in recognizing MDA-MB-231 breast cancer cells and, importantly, this recognition can be measured by SERS experiments. To characterize, on a molecular scale, the interaction between PD-L1 and peptide functionalized nanostructures, we performed molecular dynamics (MDs) simulations, studying the features of peptide monolayers bound on gold surfaces in the absence and presence of PD-L1. The results obtained allow us to explain why the nature of the linker plays a fundamental role in the binding and why a peptide carrying the same amino acids as CPL002 but with a different sequence (scrambled) is much less active than CLP002. These results open the way to an in silico evaluation of the key parameters that regulate the binding of PD-L1 useful for cancer recognition. Full article

Background/Objectives: The isatin nucleus is a privileged scaffold in drug discovery, particularly due to its proven relevance in anticancer research. Developing reusable heterogeneous 3D catalysts for drug synthesis represents a critical challenge in both industrial and academic contexts. This multi and interdisciplinary work aimed to design and synthesize a novel 3D-printed silica-based porous catalyst functionalized with palladium, evaluate its catalytic performance in isatin drug synthesis, and assess the antiproliferative activity of the resulting compounds against tumor cell lines such as HeLa, MCF-7, and MDA-MB231. Methods: The novel multifaceted approach to synthesizing this heterogeneous catalyst involved the surface growth of a metal–organic framework (ZIF-8) on 3D-printed silica support, followed by potassium silicate coating and pyrolysis. Results: After detailed physicochemical characterization, the catalyst was tested in challenging “double” palladium-catalyzed cross-coupling reactions (Suzuki, Stille, and Heck), demonstrating robustness, reusability, and high efficiency in producing bis-1,5-aryl, alkynyl, and alkenyl-isatin derivatives. Importantly, no leaching of palladium species was detected during the catalytic cycles, further underscoring the stability of the system. These isatin-based compounds exhibited remarkable cytotoxicity, with selective molecules achieving nanomolar potency against MCF-7 cells, surpassing reference drugs such as doxorubicin and sunitinib. Conclusions: This study not only introduces a novel strategy for fabricating porous heterogeneous catalysts from sintered surfaces but also highlights new biomolecules with promising applications in cancer research. Full article

Dual inhibition of cyclooxygenase-2 (COX-2) and lipoxygenase (LOX) is a recognized strategy for enhanced anti-inflammatory effects in small molecules, offering potential therapeutic benefits for individuals at risk of dementia, particularly those with neurodegenerative diseases, common cancers, and diabetes type. Alzheimer’s disease (AD) is the most common cause of dementia, and the inhibition of acetylcholinesterase (AChE) is a key approach in treating AD. Meanwhile, Caspase-3 catalyzes early events in apoptosis, contributing to neurodegeneration and subsequently AD. Structure-based virtual screening of US-FDA-approved molecules from the ZINC15 database identified clozapine (CLOZ) as the dual inhibitor of COX-2 and AChE, with significant binding affinity. Further molecular docking of CLOZ in the active site of LOX and Caspase-3 also showed significant binding potential. Further, the results from molecular docking were validated using molecular dynamics simulation (MDS) studies, confirming the results from molecular docking. The results from MDS showed good binding potential and interactions with key residues. The CLOZ was further assessed using lipopolysaccharide (LPS)-challenged rats treated for thirty days at doses of 5 and 10 mg/kg, p.o. The results demonstrated modulation of COX-2, 5-LOX, AChE, Caspase-3, and MDA in LPS-induced brains. Additionally, the expression level of IL-10 was also measured. Our results showed a significant decrease in the levels of COX-2, 5-LOX, AChE, Caspase-3, and MDA. Our results also showed a significant decrement in the pro-inflammatory markers NF-κB, TNF-α, and IL-6 and an improvement in the levels of anti-inflammatory markers IL-10 and TGF-β1. Overall, the findings indicate that CLOZ has potential for neuroprotective effects against LPS-treated rats and can be explored. Full article

Background/Objectives: Trastuzumab is an effective therapeutic intervention for treating HER2-positive breast cancers. The cost-effectiveness, global demand, and patent expiration of trastuzumab have led to the inflow of its biosimilars in the global market. With the rise of biosimilars in the biopharmaceutical market, it has become crucial to ensure that the biosimilar is at par with the original monoclonal antibody (mAb)in terms of efficacy, safety, and quality. Bioassay is one of the critical quality attributes (CQAs), hence developing a reliable and robust bioassay is essential for the evaluation of their biological activity and the harmonization of the quality of these biologics, supporting their safe and effective use in clinical practice. Methods: The present study aimed to develop a robust cell-based bioassay to assess the bioactivity of trastuzumab and its biosimilars for quality control testing. For this purpose, molecular characterization of different HER2-positive breast cancer cell lines of SKBR3, BT474, MDA-MD-453, MDA-MB-175, MCF-7, and MDA-MB-231 was performed to select a suitable cell line for the cell-based bioassay. Results: The SKBR3 cell line was found to express the HER2 receptors significantly higher in comparison to the other cell lines, and it was thereby selected for further bioassay optimization. The biological activity of trastuzumab was determined using the inhibition of proliferation (IOP) assay on the SKBR3, which was optimized based on the parameters of cell seeding density, drug dilution range, and incubation time, and it was further validated as per the compendial guidelines and found valid for the parameters of specificity, accuracy (% relative bias = 0.0067%), precision (repeatability: % GCV = 1.21%), linearity (R2 = 0.99), and range (50% to 200%). Additionally, the biological activity of different trastuzumab biosimilars was assessed using the validated IOP assay and compared to the HER2 binding assay performed by flow cytometry. The biological activity of different trastuzumab biosimilars was found to be comparable to the WHO primary reference standard of trastuzumab in terms of its relative potency using the IOP assay and binding assay by flow cytometry. Conclusions: Thus, an economic and robust cell-based bioassay method was successfully developed to assess the bioactivity of trastuzumab and its biosimilars. Full article

During the dormant period of peach trees in winter, flower buds exhibit weak cold resistance and are susceptible to freezing at low temperatures. Understanding the physiological and molecular mechanisms underlying the response of local peach buds to low-temperature adversity is crucial for ensuring normal flowering, fruiting, and yield. In this study, the experimental materials included the conventional cultivar ‘Xia cui’ (XC) and the cold-resistant local resources ‘Ding jiaba’ (DJB) peach buds. The antioxidant enzyme activity, levels of malondialdehyde (MDA), proline (Pro), and hydrogen peroxide content (H₂O₂) were determined in peach buds at different dormancy periods. Transcriptome sequencing was performed at three dormancy stages: the dormancy entry stage (FD), deep dormancy release stage (MD), and dormancy release stage (RD). Additionally, transcriptome sequencing was conducted to analyze gene expression profiles during these stages. Our findings revealed that compared with XC cultivars, DJB peach buds exhibited decreased MDA and H₂O₂ contents but increased superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT) activities as well as Pro content during the dormancy period. These findings suggest that cold-resistant cultivars possess significantly stronger antioxidant capacity than conventional cultivars under low-temperature stress. A total of 10,168 differential genes were annotated through transcriptome sequencing. Among them, 4975 were up-regulated while 5193 were down-regulated. The differentially expressed genes associated with low-temperature response in peach buds are primarily enriched in plant hormone signal transduction pathway and phenylpropane synthesis pathway. Key differentially expressed genes related to cold resistance include ARF2, GH3, and SAPK2, and differentially expressed transcription factors mainly belong to the AP2/ERF-ERF, bHLH, and C2H2 families. This study provides a theoretical foundation for understanding the key genes involved. Full article

A series of target 4-substituted-5-(2-(pyridine-2-ylamino)ethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thiones and their chloro analogs 7–21 were synthesized in a reaction of the selected aldehydes with the corresponding 4-amino-1,2,4-triazole-3-thiones 5 and 6, which were obtained from 3-(pyridin-2-ylamino)propanoic acid (3) or 3-((5-chloropyridin-2-yl)amino)propanoic acid (4), respectively, with thioacetohydrazide. The antibacterial and antifungal activities of the synthesized hydrazones were screened against the bacteria Escherichia coli, Staphylococcus aureus, and Mycobacterium luteum and the fungi Candida tenuis and Aspergillus niger by agar diffusion and serial dilution methods. 4-Amino-5-(2-((5-chloropyridin-2-yl)amino)ethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (6) and 4-(benzylideneamino)-5-(2-(pyridin-2-ylamino)ethyl)-2,4-dihydro-3H-1,2,4-triazole-3-thione (7) were identified as exceptionally active (MIC 0.9 µg/mL) against the fungus C. tenuis. 5-Chloropyridine derivatives bearing 4-benzylidene 8, 2-nitrobenzylidene 10, pyridinylmethylene 16, and 4-methylthiobenzylidene 21 moieties showed very high antibacterial activity (MIC 3.9 µg/mL) against the M. luteum strain. The cell viability screening of the synthesized compounds using triple-negative breast cancer MDA-MB-231 and glioblastoma U-87 cell lines by MTT assay identified three active hydrazones, of which 5-(2-(pyridin-2-ylamino)ethyl)-4-((pyridin-3-ylmethylene)amino)-2,4-dihydro-3H-1,2,4-triazole-3-thione (15) had the highest effect on the viability of cells (IC₅₀ value 39.2 ± 1.7 μM against MDA-MD-231). The in silico molecular modeling results suggested that these three most active hydrazones might have influenced the mitogen-activated protein kinase pathway through the inhibition of BRAF and MEK serine–threonine protein kinases. 5-(2-((5-Chloropyridin-2-yl)amino)ethyl)-4-((4-(methylthio)benzylidene)amino)-2,4-dihydro-3H-1,2,4-triazole-3-thione (21) demonstrated the highest affinity among them. Full article

This study tested the ISL against renal damage induced by a high-fat diet (HFD) and explored its underlying mechanisms. Adult male rats were assigned to four groups: (1) control on a standard diet (STD), (2) ISL on STD (30 mg/kg), (3) HFD, and (4) HFD + ISL (30 mg/kg). After 12 weeks of dietary intervention, ISL treatment led to significant reductions in body weight gain, visceral fat, and glucose and insulin levels in HFD-fed rats. Notably, ISL decreased serum urea and creatinine, increased serum albumin, and improved urinary profiles by lowering the urinary albumin and the albumin/creatinine ratio. Histological analyses revealed that ISL enhanced the glomerular structure and mitigated tubular damage, as evidenced by reduced urinary excretion of the kidney injury markers NGAL and KIM-1. Additionally, ISL significantly lowered cholesterol, triglycerides, and free fatty acids in both the control and HFD groups while also decreasing oxidized low-density lipoproteins (ox-LDLs) and malondialdehyde (MDA). Importantly, ISL enhanced renal antioxidant levels, increasing glutathione (GSH), superoxide dismutase (SOD), and catalase (CAT). Moreover, ISL downregulated mRNA levels of MD-2, Toll-like receptor-4 (TLR-4), and NF-κB, leading to reduced NF-κB p65 levels in renal tissues. In conclusion, ISL offers substantial protection against HFD-induced renal toxicity through mechanisms that attenuate metabolic stress, enhance antioxidant defenses, and inhibit the MD-2/TLR4/NF-κB inflammatory pathway. Full article

Metabolic disorders (MDs) include disease states such as diabetes mellitus, obesity, dyslipidemia, hyperuricemia, etc., affecting about 30% of the planet’s population. The purpose of the present study was to investigate the protective potential of Cicerbita alpina leaf extract (ECA) against chemically induced type 2 diabetes in Wistar rats. Additionally, some biochemical parameters in the blood serum and liver, as well as histopathological investigation, were also performed. Quantitative analysis of the major compounds in the used extract was performed using ultrahigh-performance liquid chromatography-diode array detection (UHPLC-DAD) analyses using the external standard method. C. alpina extract revealed a beneficial effect on MDs, lowering blood sugar levels and MDA quantity in the liver, increasing the reduced glutathione level, and increasing antioxidant enzyme activity. Cichoric acid (CA) (91.93 mg/g dry extract (de) ± 4.64 mg/g de) was found to be the dominant compound in the extract, followed by caftaric (11.36 ± 2.10 mg/g de), and chlorogenic acid (CGA) (9.25 ± 0.05 mg/g de). In conclusion, C. alpina leaf extract (ECA) is rich in caffeoyltartaric and caffeoylquinic acids and provides beneficial effects on the diabetic animal model. Full article

Marek’s disease (MD), caused by the Marek’s disease virus, is a lymphoproliferative disease in chickens that can be controlled by vaccination. However, the current vaccines can limit tumor growth and death but not virus replication and transmission. The present study aimed to evaluate host responses following intramuscular injection of an mRNA vaccine encoding gB and pp38 proteins of the MDV within the first 36 h. The vaccine was injected in low and high doses using prime and prime-boost strategies. The expression of type I and II interferons (IFNs), a panel of interferon-stimulated genes, and two key antiviral cytokines, IL-1β and IL-2, were measured in spleen and lungs after vaccination. The transcriptional analysis of the above genes showed significant increases in the expression of MDA5, Myd88, IFN-α, IFN-β, IFN-γ, IRF7, OAS, Mx1, and IL-2 in both the spleen and lungs within the first 36 h of immunization. Secondary immunization increased expression of all the above genes in the lungs. In contrast, only IFN-γ, MDA5, MyD88, Mx1, and OAS showed significant upregulation in the spleen after the secondary immunization. This study shows that two doses of the MDV mRNA vaccine encoding gB and pp38 antigens activate innate and adaptive responses and induce an antiviral state in chickens. Full article