Current Pharmaceutical Design - Online First

Citrus reticulata (CR) has a long-standing role in traditional medicine, primarily due to its bioactive constituents such as hesperidin and narirutin, which are known for their antioxidant, anti-inflammatory, antibacterial, and anticancer properties.

This study investigates the anti-proliferative activity of CR water extracts against DU-145 prostate cancer cells and explores the therapeutic potential and underlying molecular mechanisms of hesperidin and narirutin in prostate cancer (PCa) and benign prostatic hyperplasia (BPH) through network pharmacology and molecular docking approaches.

Cytotoxicity assays were employed to determine the anti-cancer efficacy (IC50) of processed CR water extracts in DU-145 cells. Targets related to hesperidin, narirutin, PCa, and BPH were identified using bioinformatics platforms. Network pharmacology was applied to construct compound-target interaction networks and perform enrichment analyses (GO, KEGG, and DisGeNET) to elucidate key signalling pathways. Molecular docking was conducted to validate compound-target interactions.

Soil-processed CR extracts exhibited the strongest anti-cancer activity (IC50 = 1.789 mg/mL). Enrichment analyses identified significant pathways, including AGE-RAGE signalling, p53 signalling, inflammation, angiogenesis, and apoptosis. Molecular docking confirmed strong binding affinities of hesperidin and narirutin to the predicted targets.

Based on in vitro assays and in silico analyses, processed Citrus reticulata peel extracts may exert beneficial effects in both prostate cancer and benign prostatic hyperplasia. The soil-processed water extract demonstrated the most significant potential. The results suggest that the major compounds may act on several key proteins and pathways related to apoptosis and inflammation. However, further experimental and in vivo studies are needed to confirm their efficacy and safety.

Anti-proliferative assays, network pharmacology, and molecular docking collectively demonstrate that hesperidin and narirutin from CR show strong therapeutic potential against PCa and BPH. The findings highlight the involvement of AGE-RAGE and p53 signalling pathways and support the potential of these compounds in future drug development.

The current study aimed to synthesize and identify the biological activities of pyrazine-piperidine amide pharmacophore derivatives against non-small lung carcinoma (Calu-6) cells.

The combinatorial formulation was prepared by an active mixture of different chemical substituents, and five (6A-E) different molecules were synthesized. The chemical structures were confirmed by Fourier transform infrared (FT-IR) spectroscopy and proton nuclear magnetic resonance (H1) spectroscopy.

These compounds were also screened for cytotoxicity against the Calu-6 cell line. Compounds 6B and 6D displayed potent cytotoxicity, with IC50 Values of 45.21 µM and 89.64 µM, respectively. Cellular uptake and apoptotic studies using compound microscopy and flow cytometry revealed that cell damage gradually increased, leading to cell death. Compound 6B at 25 µM and 50 µM had 75.3% and 65.3% viability, 8.61% and 9.85% apoptotic effects, 12.05% and 21.4% late apoptosis, and 4.02% and 3.4% necrosis, respectively.

Compound 6B was found to significantly enhance cell cycle arrest at the G2/M phase. Additionally, real-time RT-PCR and western blot analyses further confirmed the enhanced expression of apoptotic markers, such as caspase-3 and 8, as well as the antiproliferative gene p53.

These findings indicate that compound 6B has a promising anticancer effect on lung cancer.

3D bioprinting is a rapidly evolving technology in healthcare, especially in the fields of regenerative medicine, pharmaceutical research, and tissue engineering. This technique utilizes bioinks to fabricate three-dimensional structures that replicate the architecture and function of natural tissues through layer-by-layer additive manufacturing. This review aims to explore the current advancements, challenges, and future directions of 3D bioprinting.

A comprehensive review of the literature was conducted, focusing on various approaches to 3D bioprinting, including biomimicry, scaffold-based, scaffold-free, autonomous self-assembly, organ-on-a-chip, and microtissue building block techniques. Additionally, advancements in bioink development and different bioprinting technologies such as inkjet, extrusion, laser-assisted, stereolithography, acoustic, and magnetic bioprinting were analyzed.

The literature highlights significant progress in bioprinting technologies, demonstrating the transition of 3D bioprinting from a theoretical innovation to a practical tool in tissue engineering and regenerative medicine. Advances in printing precision, cell-material interactions, and bioink formulations are bringing the technology closer to clinical applications.

Key challenges remain—most notably creating robust vascular networks, scaling up production without loss of function, and ensuring that engineered tissues integrate seamlessly with a patient’s own biology. Still, the potential payoffs are enormous, from tailor-made implants and on-demand drug testing platforms to fully functional organ replacements.

3D bioprinting stands poised to transform personalized medicine and regenerative therapies. Achieving this vision will require sustained, interdisciplinary efforts to refine printing methods, innovate bioink chemistry, and master tissue maturation.

Obesity represents a significant health and lifestyle issue worldwide. White and brown adipocytes, which originate from resident mesenchymal stem cells (MSCs), are critically involved in the process of adipogenesis.

Human umbilical cord-derived mesenchymal stem cells (hUCMSCs) were utilized to investigate epigenetic modifications associated with adipogenic differentiation. Briefly, histone acetylation and/or methylation pattern of hUCMSCs were evaluated with histone deacetylase inhibitor Trichostatin A (TSA) for cell viability, death rate, and adipogenic commitment.

Inhibition of histone deacetylation was accompanied by a reduction of the global methylation pattern compared to the baseline levels in untreated cells. These changes decreased cell viability at 36 hrs, while reciprocally increasing the rate of cell death from 24 hrs. Most importantly, TSA-treated cells demonstrated diminished adipogenic differentiation compared to normal cells post-induction.

Epigenetic remodeling triggered by inhibition of histone deacetylase led to reduced DNA methylation. The increased cytotoxicity, impairing cell survival due to alteration in chromatin state, reduced adipogenic differentiation potential in TSA-treated cells, promoting disruption of normal lineage commitment pathways.

Taken together, the results show a possible anti-obesity effect of histone deacetylation inhibitors (HDCAs) in MSCs, resulting in depletion and restriction of their adipogenic differentiation.

For centuries, Traditional Chinese Medicine has been a subject of extensive research for its healing properties, including its effects against viruses. The pollen of Typha angustifolia emerges as a notable natural source of antiviral agents, with earlier investigations focusing on its antioxidant and anti-inflammatory properties, which are associated with flavonoids and phenolics that facilitate electron transfer. These bioactive compounds could potentially disrupt viral entry and replication, thereby necessitating further studies.

Molecular docking analysis was conducted on 11 compounds from T. angustifolia targeting the entry protein of dengue virus, the NS5B polymerase of hepatitis C virus, and the RdRp of Japanese encephalitis virus. The binding affinity was evaluated through LibDock score assessments, and simulations of molecular dynamics (RMSD and RMSF) were performed to analyze the stability of the complexes.

Naringenin was consistently identified as one of the highest binders for all three viral proteins, achieving the top score for the RdRp of Japanese encephalitis (129.288). Isorhamnetin showed the greatest binding affinity for the hepatitis C NS5B polymerase (120.827), exceeding that of sofosbuvir (120.629), while isorhamnetin-3-O-rutinoside displayed strong binding to the dengue viral entry protein (97.0838). Molecular dynamics confirmed the stability of ligand-protein interactions, underlined by sustained van der Waals and electrostatic forces.

These findings underscore naringenin as a versatile antiviral candidate, with other flavonoids exhibiting specific effectiveness that could facilitate multitarget inhibition approaches. This polypharmacological potential of flavonoids aligns with their established antiviral properties, although confirmatory experimental studies are critical.

Naringenin emerged as the most potent and reliable antiviral agent among the compounds of T. angustifolia, particularly against the RdRp of Japanese encephalitis. These computational insights validate T. angustifolia pollen as a promising natural antiviral resource, warranting further validation through in vitro and in vivo studies.

Myocarditis (MC) is an inflammatory cardiomyopathy with high morbidity and mortality. Current treatment options for MC have limitations and side effects, necessitating the exploration of new therapies. Traditional Chinese Medicine (TCM), particularly Huaiqihuang Granules (HQH), has shown promise due to its anti-inflammatory, antioxidative, and anti-apoptotic properties. However, the application in cardiovascular diseases remains underexplored.

We employed network pharmacology, molecular docking, and Molecular Dynamics (MD) simulations to evaluate HQH’s effects on MC. This involved identifying bioactive components and therapeutic targets, conducting enrichment analyses, and performing molecular docking and MD simulations to validate the interactions between HQH components and MC-related targets.

A total of 57 bioactive components in HQH and 143 potential therapeutic targets for MC were identified. Enrichment analyses revealed that HQH’s potential treatment effects on MC involve various processes and pathways, including response to lipopolysaccharide, peptidase activity, the extracellular region, and pathways in cancer. Molecular docking indicates that Physalin A, sibiricoside A_qt, zhonghualiaoine 1, and methylprotodioscin_qt, along with ALB, PTGS2, AKT1, ESR1, and MMP9, may serve as key therapeutic components and targets. MD simulations confirmed strong interactions between HQH’s core components and MC-related targets, supporting their potential therapeutic effects.

This study suggests that HQH exerts therapeutic effects against MC through multi-target mechanisms and stable targets. These findings provide valuable insights into alternative treatment strategies for MC, offering a foundation for further research and clinical exploration.

This study confirms that HQH can influence MC through various active components and multiple therapeutic targets.

Diabetic Nephropathy (DN) is a Chronic Kidney Disease (CKD), and its main pathological changes are renal tubular injury and glomerulosclerosis. Semen Ziziphi Spinosae (SZS) is the seed of Ziziphus jujuba var. spinosa (Bunge) Hu ex H.F. Chow. As a triterpene saponin, Jujuboside A (Ju A) is the main active substance isolated from SZS. This study sought to investigate the potential effect and mechanism of Jujuboside A against DN.

The anti-apoptotic effects of Ju A on renal parenchymal cells of DN were examined by in vivo and in vitro studies. Molecular docking and Molecular Dynamics (MD) simulation revealed that Ju A could bind to TNF-α and Caspase-3 via forming stable receptor-ligand complexes, respectively. Immunofluorescence (IF) staining and ELISA detection were carried out to investigate the potential mechanisms by which Ju A exerted its amelioration effect on DN.

Our study showed that, accompanied by the restored renal function, Ju A inhibited apoptosis of renal tubules and glomeruli in vivo and in vitro. Network pharmacology revealed that 42 overlapping targets were related to Ju A and DN. Among them, IL6, IL1B, TNF, VEGFA, EGFR, ALB, IGF1, FGF2, CASP3, and ESR1 were the top 10 targets. Ju A could bind to TNF-α and Caspase-3 via forming stable receptor-ligand complexes, respectively, as demonstrated by molecular docking and MD simulation. Ju A decreased the protein levels of TNF-α and IL-1β in renal tubules and glomeruli of diabetic mice, and in HG-cultured HK-2 cells and podocytes, leading to the alleviation of inflammation. Besides, the up-regulated relative phosphorylation levels of NF-κB p65 and cleaved caspase-3 were also down-regulated by Ju A in vivo and in vitro.

The research showed that Ju A had a high affinity for Caspase-3 and TNF-α, and the underlying mechanism of Ju A against DN was the inhibition of apoptosis in renal tubular epithelial cells and podocytes. These findings strengthened the evidence that Ju A could be a potential treatment strategy for DN and offered opportunities for therapeutic advances in the field.

Ju A could inhibit apoptosis and alleviate inflammation of renal parenchymal cells by inactivating the TNF-α/NF-κB p65/Caspase-3 signaling pathway, exerting renal protective effect against DN.

Despite significant advances in the comprehensive treatment of nasopharyngeal carcinoma (NPC), local recurrence or distant metastasis still occurs in a considerable proportion of patients, leading to poor outcomes and posing a significant clinical challenge. The current therapeutic agent, Triptonide (TN), has shown potential efficacy in modulating cellular autophagy, suggesting its therapeutic promise for treating NPC. However, the precise molecular targets and mechanisms underlying TN’s role in NPC remain to be elucidated.

Initially, relevant targets for TN in the treatment of NPC were identified through public databases. Next, network pharmacology and bioinformatics analyses were employed to pinpoint the top 15 hub targets and critical signaling pathways involved in TN’s therapeutic action. Finally, experimental validation, including a range of molecular assays, was conducted to investigate the cellular effects of TN treatment, such as apoptosis induction, migration inhibition, Caspase-3 activation, mitochondrial dysfunction, autophagy-related gene expression, and TFAM level detection, thereby confirming the essential genes and pathways.

A total of 31 potential molecular targets for TN in NPC were identified, with 27 genes confirmed through autophagy-related gene analysis. Among these, the top 15 hub genes included RELA, CASP8, NFKBIA, PPARG, PTGS2, MAPK14, MAPK8, HDAC1, ERBB2, CASP1, TERT, AR, CDK1, PGR, and HDAC6. TN was found to activate the MAPK signaling pathway. In vitro, TN induced NPC cell apoptosis via increased ROS, MAPK14 activation, and Caspase-3 cleavage. It disrupted mitochondrial function (reduced membrane potential, decreased copy number, enhanced fission), inhibited mTOR and RELA phosphorylation, and promoted autophagy. TN also caused S-phase arrest, reduced CDH3, and increased CDH1. Lipoic acid partially reversed TN-induced cytotoxicity.

TN exerts anti-NPC effects primarily through MAPK pathway activation and autophagy induction. Key targets mediating these effects include RELA, CASP8, PPARG, MAPK14, MAPK8, HDAC1, ERBB2, and CASP1. The reversal by lipoic acid implicates ROS in TN's mechanism. The disruption of mitochondrial function represents a critical facet of its action.

TN demonstrates potential as a therapeutic agent for NPC, primarily through activation of the MAPK signaling pathway and autophagy. Key targets, including RELA, CASP8, PPARG, MAPK14, MAPK8, HDAC1, ERBB2, and CASP1, have been identified as critical mediators of TN’s effects, highlighting its role in promoting autophagy and enhancing NPC treatment.

There is increasing evidence that environmental factors play an important role in the pathogenesis of hyperuricemia. However, the relationship between Brominated Flame Retardants (BFRs) and serum uric acid and hyperuricemia remains unclear.

This study used data from 7996 National Health and Nutrition Examination Survey (NHANES) participants from 2005 to 2016. Ten BFRs, including PBB153 and PBDE28, were included in the analysis. Multivariate logistic regression, subgroup analysis, Spearman correlation analysis, Weighted Quantile Sum (WQS), and Bayesian Kernel Machine Regression (BKMR) were used to assess the association between BFRs and hyperuricemia. We also evaluated the mediating role of the Systemic Immunoinflammatory Index (SII) in the relationship between BFRs and hyperuricemia.

Results show that, after adjusting for all covariates, PBDE47, PBDE99, PBDE100, and PBDE154 were significantly associated with hyperuricemia risk. The results of the WQS regression and BKMR model showed a significant positive correlation between exposure to mixed BFRs and hyperuricemia risk. PBDE183 (weight: 38%) was found to have the highest weight in the mixture. Further mediating analysis showed that the relationship between PBDE28 and PBDE183 exposure and hyperuricemia risk was mediated by SII.

Exposure to BFRs increases the risk of hyperuricemia, which may be mediated by inflammation. Therefore, future research should further explore the potential mechanisms underlying the association between BFR exposure and hyperuricemia risk.

Exposure to BFRs may increase the risk of hyperuricemia. Large-scale prospective cohort studies and experimental research are needed to confirm the relationship between BFRs and hyperuricemia.

This study aimed to synthesize and characterize copper oxide nanoparticles (CuO NPs) using Rhus punjabensis extract and chemical methodologies. The comparative nephrotoxicity of green-synthesized CuO NPs (G-CuO-NPs) and chemically synthesized CuO NPs (C-CuO NPs) were examined in Sprague-Dawley rats and their offspring following oral administration during pregnancy and lactation.

Fourier Transform Infrared Spectroscopy (FT-IR), Scanning Electron Microscopy (SEM), Transmission Electron Microscopy (TEM), and X-ray Diffraction (XRD) were employed to examine the morphology, dimensions, and functional groups of the fabricated CuO NPs. To assess the relative nephrotoxicity of G-CuO-NPs and C-CuO-NPs at doses of 50 and 100 mg/kg, twenty-five rats were randomly allocated to five groups (designated as G1, G2, G3, G4, and G5), with each group comprising one male and four female animals for mating purposes. Nephrotoxicity of both parental and offspring animals was evaluated by examining their antioxidant status, total protein content, lipid peroxidation, genotoxicity, serum biochemistry, and histopathology.

FT-IR confirmed the synthesis of CuO NPs, while TEM and SEM revealed that G-CuO NPs were spherical and C-CuO NPs were oval. The XRD analysis showed that both NPs had a monoclinic structure. The crystalline dimensions of G-CuO NPs were 36.6 nm, and 32.85 nm for C-CuO NPs. C-CuO NPs showed dose-dependent toxicity in both parents and pups, causing a disturbance in the antioxidant balance, reducing protein content, and inducing lipid peroxidation and genotoxicity in the renal tissues. The morphological architecture of the parents’ kidneys and renal function were evaluated. G-CuO NPs, on the other hand, showed mild toxicity only in the parents.

The findings indicate that G-CuO NPs exhibit biocompatibility and are suitable for biological applications. This study underscores the compatibility of plant-derived metallic nanoparticles with living systems and paves the way for investigating their potential applications in contexts where toxicity limits the use of nanoparticles.

Based on these findings, the biocompatibility of green-synthesized CuO NPs was determined, and they did not induce nephrotoxicity in both parents and their offspring. In contrast, chemically synthesized CuO NPs, when administered at higher concentrations, were found to cause nephrotoxicity, which may also be transmitted to the offspring through lactation.

The COVID-19 pandemic, caused by SARS-CoV-2, has highlighted the urgent need for effective antiviral and anti-inflammatory therapies. Spiropyridine derivatives containing a chalcone moiety have shown potential in targeting key enzymes involved in viral replication and inflammation.

To evaluate the inhibitory effects of synthesized spiropyridine derivatives on SARS-CoV-2 main protease (Mpro), secreted phospholipase A2 (sPLA2), and cytosolic phospholipase A2 (cPLA2), and to assess their impact on inflammatory and oxidative stress markers in LPS-treated lung cells.

To develop novel therapeutic agents that can effectively manage COVID-19 and related inflammatory conditions.

The synthesized compounds (1-3) were tested for their inhibitory activity against SARS-CoV-2 Mpro, sPLA2, and cPLA2 using in vitro assays to determine IC50 values. Inflammatory markers (COX-2, IL-2, IL-4, TGF-1β, TNF-α) and oxidative stress markers (GSH, SOD, GR, MDA) were measured in LPS-treated lung cells. Gene expression levels of sPLA2 and cPLA2 were also assessed. Molecular docking studies were conducted to analyze the binding affinities and interactions of the compounds with the target enzymes.

Compounds 1-3 showed significant inhibitory activity against SARS-CoV-2 Mpro with IC50 values of 19.85 µM, 7.31 µM, and 3.73 µM, respectively. For comparison, baicalein's IC50 value was 13.63 µM. Additionally, these compounds inhibited sPLA2 with IC50 values of 8.36 µM, 7.31 µM, and 3.73 µM, and cPLA2 with IC50 values of 20.44 µM, 6.02 µM, and 4.61 µM, respectively. Baicalein's IC50 values for sPLA2 and cPLA2 were 11.73 µM and 5.89 µM, respectively. In LPS-treated lung cells, compounds 1-3 significantly reduced COX-2 by up to 90.12%, IL-2 by 74.19%, IL-4 by 79.51%, TGF-1β by 44.57%, and TNF-α by 68.49%. They enhanced GSH by up to 194%, SOD by 357.19%, and GR by 445.87%, while reducing MDA by 77.90%. Gene expression of sPLA2 and cPLA2 was significantly downregulated by up to 82.31% and 64.59%, respectively. Molecular docking studies revealed binding affinities of -28.20, -28.20, and -28.07 kcal/mol for SARS-CoV-2 Mpro; -16.72, -17.21, and -15.89 kcal/mol for sPLA2; and -65.66, -66.95, and -79.24 kcal/mol for cPLA2, respectively.

The results demonstrate that the structural integration of a spiropyridine core with a chalcone moiety yields compounds with superior multi-target inhibitory activity. The potent antiviral, anti-inflammatory, and antioxidant effects are significantly correlated with their strong binding interactions with the active sites of Mpro, sPLA2, and cPLA2, as validated by molecular docking. These findings align with and extend current research on targeting host-inflammatory pathways alongside viral replication for COVID-19 management.

The synthesized spiropyridine derivatives containing a chalcone moiety exhibit potent antiviral, anti-inflammatory, and antioxidant properties. These findings suggest that these compounds could be promising therapeutic agents for managing COVID-19 and related inflammatory conditions. Future studies should focus on in vivo experiments, clinical trials, and structural optimization to further develop these compounds for clinical use.

Millions of people have died from zoonotic illnesses, like COVID-19 and Nipahvirus infection (NiV), throughout history. Fruit bats (Pteropus sp.) are the main reservoir host for NiV, an RNA virus belonging to the Henipavirus group, which causes extremely infectious illnesses, such as COVID-19. NiV outbreaks have posed significant public health concerns, especially in South and Southeast Asia. The Nipah virus (NiV) infection is caused by a virus that belongs to the Paramyxoviridae family's Henipavirus genus. It is the source of zoonosis, which causes respiratory and neurological symptoms.

This study has reviewed the epidemiology, pathophysiology, genetic diversity, and phylogenetics of NiV. It has explored NiV’s clinical features, cellular monitoring, infection factors, and the virus’ reservoir host.

Phylogenetic analysis has identified two circulating NiV lineages. Additionally, the study has examined the role of phytochemicals in combating viral infections. Despite the absence of a focused therapy for COVID-19, phytochemicals have been investigated for their potential antiviral properties. Evidence suggests that plants and their components may possess resistance against NiV by modulating the immune system and inhibiting viral replication.

The investigation into plant-derived compounds has offered a novel direction for NiV treatment, potentially enhancing viral resistance through immune modulation. Continued research on natural antivirals could bridge current gaps in therapeutic options for emerging zoonotic diseases.

The study has highlighted the transmission risk, detection challenges, and the potential of phytochemicals in managing NiV infections. The therapeutic potential of plants and their antiviral properties offer promising insights into future treatments for serious viral diseases, like NiV.

Wound healing is a complex and dynamic biological process involving hemostasis, inflammation, proliferation, and tissue remodeling. Conventional wound dressings provide only passive protection and fail to maintain an optimal healing microenvironment. Synthetic polymers, such as polyvinyl alcohol (PVA), polycaprolactone (PCL), poly(lactic-co-glycolic acid) (PLGA), and polyethylene glycol (PEG), have emerged as promising materials in advanced wound care due to their tunable physicochemical properties, biocompatibility, and enhanced therapeutic functionality.

This review aims to evaluate the potential of synthetic polymers in wound healing applications, focusing on their structural and functional advantages, challenges, and opportunities in the development of next-generation wound dressings.

A comprehensive literature review was conducted on recent developments in polymer-based wound dressings. In this review, we conducted a systematic literature search across Google Scholar, ScienceDirect, Scopus, Web of Science, and PubMed for publications between 2015 and 2025. The search strategy employed keywords, such as “wound healing”, “polyvinyl alcohol”, “polycaprolactone”, “poly(lactic-co-glycolic acid)”, “polyethylene alcohol”, “physicochemical characteristics”, “drug delivery capabilities”, and ” clinical trial” to capture the research landscape.

Synthetic polymers demonstrated significant potential in overcoming limitations of natural biomaterials, such as poor mechanical strength and rapid degradation. PEG-based hydrogels exhibited excellent hydrophilicity and sustained drug release. PCL scaffolds offered mechanical durability and supported tissue regeneration. PLGA allowed controlled therapeutic release through tunable degradation, while PVA ensured prolonged wound protection due to its structural stability. Polymer modifications, including crosslinking and blending, further enhanced wound healing efficacy.

Synthetic polymers provide versatile platforms for designing multifunctional wound dressings with improved healing outcomes. Future research should emphasize biodegradable, patient-specific, and smart wound dressings integrating controlled drug delivery, infection prevention, and angiogenic stimulation, thereby revolutionizing wound management practices.

Nitrergic transmission and oxidative stress are complicated factors in the seizure’s pathophysiology. Syringic acid has been revealed to exert numerous pharmacological properties, including neuroprotective effects. Hence, this research was designed to explore the anticonvulsant effects of syringic acid, focusing on its possible impact on nitrergic transmission and oxidative stress in the prefrontal cortex (PFC) in mice that underwent induction of seizure using pentylenetetrazole (PTZ).

Forty male NMRI mice were randomly divided into five groups, including mice that received saline containing Tween 80 at a concentration of 1% (10 ml/kg), syringic acid at doses of 10, 20, and 30 mg/kg, and diazepam (10 mg/kg). Syringic acid was dissolved in saline containing Tween 80 at a concentration of 1%. All drugs were injected intraperitoneally one hour before seizure induction by PTZ. Seizure threshold, total antioxidant capacity (TAC), nitrite, and malondialdehyde (MDA) levels, as well as inducible nitric oxide synthase (iNOS) and neuronal nitric oxide synthase (nNOS) gene expressions, were assessed in the PFC.

Syringic acid increased the seizure threshold and TAC, whereas it decreased MDA and nitrite levels in the PFC samples. Furthermore, syringic acid diminished the expression of iNOS and nNOS genes in the PFC.

Oxidative/nitrosative stress, which is involved in the pathophysiology of seizure, was alleviated by syringic acid.

It was concluded that, at least partially, the anticonvulsant property of syringic acid was mediated through the mitigation of oxidative stress and nitrergic transmission in the PFC in PTZ-induced seizures in male mice.

The purpose of this research is to review and evaluate both traditional and emerging biomarkers used in the diagnosis, monitoring, and treatment of liver diseases. The study aims to highlight how these biomarkers—such as liver enzymes, microRNAs, exosomes, and fibrosis-related proteins—can improve early detection, track disease progression, and support personalized treatment strategies for better patient outcomes.

This study uses a literature review to analyze both traditional (ALT, AST, ALP, bilirubin, etc.) and emerging biomarkers (microRNAs, exosomes, CRP, IL-6, MMPs, TIMPs) in liver disease. It focuses on their role in diagnosis, disease monitoring, and personalized treatment planning.

Traditional biomarkers (ALT, AST, ALP, bilirubin, albumin) are key for liver function assessment. Emerging markers like microRNAs, exosomes, MMPs, and TIMPs improve early detection and disease monitoring. Together, they enhance diagnostic accuracy and support personalized treatment.

The combination of traditional and novel biomarkers improves early detection, accurate diagnosis, and personalized treatment of liver diseases. New biomarkers, such as microRNAs and exosomes, offer higher sensitivity and specificity, enabling non-invasive diagnostics. The findings align with current research trends that promote the use of molecular and extracellular markers. These biomarkers provide deeper insights into liver disease mechanisms, particularly in fibrosis and hepatocellular carcinoma.

Traditional biomarkers are essential for liver assessment, while new ones like microRNAs, exosomes, MMPs, and TIMPs improve early diagnosis and monitoring. They support personalized care but need further validation for routine use.

The Xianling Gubao capsule (XLGB), a traditional Chinese medicine formulation approved by the China Food and Drug Administration, has been effectively used to treat two common medical conditions: osteoarthritis (OA) and osteoporosis (OP). However, due to the complex ingredients, the molecular mechanisms underlying its therapeutic effects for OA and OP remain unknown.

This study identified XLGB-related therapeutic target genes and pathways for OA and OP by using bioinformatics and network pharmacology. Molecular docking assessed the interactions between core genes and compounds, while quantitative real-time PCR and Western blotting analyses validated the mRNA and protein expression of key target genes.

Bioinformatics analysis identified 473 unique genes common to OA and OP. Network pharmacology analysis identified 30 intersecting genes as the principal target genes for anti-OA and anti-OP effects. Ten hub genes were identified using protein-protein interaction as potential therapeutic targets. These genes were related to transcription regulation and enriched in certain signaling pathways, such as interleukin-17 and tumor necrosis factor. Molecular docking analysis revealed danshenxinkun B to exhibit a strong affinity for Ptgs2, Fos, and Tnfaip3, while miltirone displayed a strong affinity for Ptgs2. The experimental results have been verified using cellular experiments.

This study showed Ptgs2, Fos, and Tnfaip3 to be mainly enriched in interleukin-17 and tumor necrosis factor signaling pathways. Moreover, danshenxinkun B and miltirone significantly modulated the expression levels of these genes.

This study has demonstrated that danshenxinkun B and miltirone may be pivotal agents in treating OA and OP by down-regulating the expressions of Ptgs2, Fos, and Tnfaip3.

Hepatitis C virus (HCV) remains a major global health challenge, driving chronic hepatitis C (CHC) progression to severe liver diseases, including hepatocellular carcinoma (HCC). Direct-acting antivirals (DAAs) have transformed HCV treatment by achieving high sustained virological response (SVR) rates. However, limitations such as resistance, reinfection, and restricted accessibility emphasize the urgent need for novel therapeutic approaches. Among HCV therapeutic targets, the NS3/4A protease is critical for viral replication and immune evasion, positioning it as a prime focus for innovative drug discovery.

A comprehensive computational approach was adopted to evaluate flavonoids, natural compounds with known antiviral and anticancer properties, as potential inhibitors of the HCV NS3/4A protease. A curated flavonoid library was subjected to virtual screening using molecular docking techniques. Top-ranked flavonoids were further assessed based on binding affinity, dissociation constants, and key protein-ligand interactions. Pharmacokinetic profiling, molecular dynamics simulations, MM/PBSA energy calculations, and principal component analysis were performed to validate the most promising candidate.

The top ten scoring flavonoids demonstrated strong binding affinities and stable interactions with key catalytic residues of the NS3/4A protease. CID 100943380 emerged as the most promising candidate, exhibiting favorable pharmacokinetic properties and sustained stability throughout molecular dynamics simulations. MM/PBSA and PCA analyses further confirmed its robust binding and conformational stability.

The findings highlight flavonoids as promising inhibitors of NS3/4A protease, supporting their potential for further antiviral development.

This investigation identifies 10 flavonoids with high potential as NS3/4A protease inhibitors, providing a basis for future biological validation and safer drug development.

Sepsis-induced acute lung injury (S-ALI) is one of the diseases with a very high fatality rate. However, the traditional Chinese medicine compound Buzhong Yiqi Decoction (BZYQD) has an excellent effect in the treatment of S-ALI. Nevertheless, its mechanism of action is still unclear. In this study, we explored the molecular mechanisms of S-ALI injury treated with buzhong yiqi decoction through network pharmacology, in combination with in vivo experimental validation.

Traditional Chinese medicine system pharmacology (TCMSP) database was used to screen thechemical composition of BZYQD and its action targets; Multiple databases were used to collect target genesfor-S-ALI, including OMIM, TTD, GeneCards, and DrugBank; The STRING database was used for the protein-protein interaction (PPI) analysis of the common targets of the BZYQD and the S-ALI; The DAVID databasewas used for GO and KEGG analysis; molecular docking was used to detect the binding capacity of corecomponents and targets. HE staining was used to visualize the pathology of lung tissue in each group; ELISA wasused to detect the levels of inflammatory factors (IL-1β, IL-6, IL-8, NF-κB and TNF-α) and oxidative stressrelatedfactors (LDH, CK-MB, SOD, GSH-Px); The qPCR and Western blot were used to examine the mRNAand protein expression of IL-1β, IL-6, TNF-α NF-κB, p-NF-κB, PI3K, p-PI3K, AKT, and IKKα.

113 chemical components and 226 targets were screened from BZYQD; 9059 S-ALI-related geneswere screened out, with a total of 228 intersecting targets between BZYQD and S-ALI. Stigmasterol, quercetin, and isorhamnetin are the core components of BZYQD, PPI analysis shows that AKT1, IL6, TNF, andIL1B are the core targets of BZYQD for treating S-ALI, and molecular docking results show that the corecomponents have high binding activity with the target; Enrichment analysis shows that these core targets arerelated to the TNF signaling pathway. In vivo experimental studies have found that BZYQD can improve thedegree of inflammatory infiltration and edema in lung tissue of S-ALI model mice, reduce the expression ofIL-6, IL-1β, IL-8, TNF-α, LDH, CK-MB, and NF-κB in serum (P0.05), as well as the mRNA and proteinexpression of IL-6, IL-1β, TNF-α, NF-κB, p-NF-κB, PI3K, p-PI3K, AKT, and IKKα in lung tissue (P0.05),and levels of SOD and GSH-Px were increased (P0.05).

The action targets of the main chemical components of BZYQD are TNF, AKT, and IL6. Thesetargets can promote the activation of PI3K and TNF pathways and mediate the occurrence of inflammationand oxidative stress, which provides inspiration for the treatment of S-ALI. However, the results of this study still need to be verified in combination with in vitro approaches.

This study suggests that the mechanism of BZYQD in treating S-ALI may be achieved by inhibiting the TNF and PI3K signaling pathway and reducing inflammation and oxidative stress levels.

Pulmonary fibrosis (PF) is a chronic pulmonary disorder with unknown etiology and an irreversible course. Traditional Chinese medicine (TCM) possesses promising clinical benefits for PF treatment through a multi-component and multi-target approach. This study evaluates the efficacy of Yangyin Yifei Tongluo Wan (YF), a traditional formulation, in the treatment of PF, and further explores the underlying mechanism.

A bleomycin (BLM)-induced PF mouse model was established. Mice were administered with low-, medium-, and high-dose YF (1.5, 3, and 6 g/kg/d, respectively). The fibrosis degree of mouse lung tissues was evaluated by morphometric measurements and hydroxyproline (HYP) analysis. Network pharmacology-based bioinformatics were employed for constructing a network involving components, targets, and disease, and YF's potential mechanism and molecular targets for PF therapy were explored. This was further validated by TUNEL staining, Western blot, RT-qPCR, and ELISA in BLM-treated mice.

YF could relieve PF in BLM-treated mice in a dose-dependent manner, evidenced by a notable decrease in collagen deposition, and collagen I and III, HYP, fibronectin, vimentin, and α-SMA expressions. Network pharmacology revealed that JAK2/STAT3 signaling pathway-mediated alveolar epithelial cell apoptosis may be a potential therapeutic target for YF in treating PF. In vivo assays confirmed that YF's anti-fibrosis effect on BLM-induced PF was ascribed to the suppression of alveolar epithelial cell apoptosis and disruption of the JAK2/STAT3 signaling pathway.

YF can block alveolar epithelial cell apoptosis through inactivation of the JAK2/STAT3 signaling, subsequently enhancing the resolution of PF.

YF may be a promising therapeutic candidate for PF treatment.

Polycystic ovarian syndrome (PCOS) is a hormonal condition that affects women of reproductive age. The purpose of this study was to identify the undiscovered molecular mechanisms by which Stachys lavandulifolia treats PCOS. Although Stachys lavandulifolia has been used to treat PCOS, its exact biological mechanism of action remains unknown.

We used a multifaceted strategy that included network pharmacology, molecular docking, and molecular dynamics simulations.

Network pharmacology discovered 68 gene targets shared by Stachys lavandulifolia bioactive chemicals and PCOS-associated genes. Subsequent KEGG and Reactome analysis identified 18 enhanced pathways, including steroid hormone production, glucose homeostasis, and insulin resistance. Key genes involved in ovarian steroidogenesis and the hypothalamic-pituitary-ovarian axis (CYP19A1, Kiss1, human androgen receptor, oestrogen receptor alpha, and HSD17B1) were chosen for molecular docking.

Molecular docking indicated that bioactive substances Myrsen, Agnol, Alpha Pyogenin, and Gamma Morolen have high binding affinities for the identified target proteins. Notably, the CYP19A1-Myrsen complex has the highest binding affinity at -9.0 kcal/mol. Additional molecular dynamics simulations indicated that the CYP19A1-Myrsen complex had increased flexibility and mobility, indicating a stable and effective association.

Our findings identify potential gene pathways and interactions through which Stachys lavandulifolia bioactive chemicals exert their therapeutic benefits in PCOS. This study establishes a solid platform for future research into Stachys lavandulifolia as a potential PCOS therapy.

Recombinant protein vaccines against infectious diseases, based on immunogenic antigen identification and employing polymeric nanoparticles as a delivery system, can provoke immune responses comparable to or better than traditional vaccines. The production of a safe and immunogenic vaccine against diphtheria was achieved by preparing sodium alginate nanoparticles containing recombinant diphtheria toxoid (CRM197).

Alginate nanoparticles loaded with CRM197 were prepared using the ionic-gelation method and thoroughly characterized. Safety and immunogenicity studies were conducted in an animal model for comparison with commercial vaccines. Antibody responses were evaluated using both qualitative and quantitative measurements, as determined by the toxin neutralization test (TNT) and indirect ELISA, respectively. IgG subclasses in the sera of immunized mice and possible pathological lesions in vital tissues of all immunized mouse groups were investigated.

Nanoparticles with or without CRM197 were synthesized by the ionic gelation method. LE and LC measurements showed ˃80% and ˃20%, respectively, indicating stable and persistent release without a bursting pattern. In vivo studies showed safety and enhanced immunogenicity in mice immunized with the CRM197-loaded sodium alginate nanoparticles, with higher levels of total anti-CRM197 IgG and subclasses than those induced by conventional vaccines.

Reducing antigen usage in vaccine production while increasing immunogenicity and safety compared with traditional vaccines are the goals of new vaccine development, which were achieved in the current study.

Engineered alginate nanoparticles loaded with recombinant diphtheria antigen (CRM197) demonstrated in vitro controlled and slow release, as well as safety and immunogenicity profiles against diphtheriain vivo. Nanoparticles containing CRM197 antigens equivalent to adult and children doses showed high levels of IgG1 and IgG2a, confirming the combined responses of the humoral and cellular immune systems.

Recent studies indicate that niclosamide demonstrates considerable promise as both an anthelmintic agent and a possible anticancer medication. Given the increasing interest in nano-sized drug delivery methods for cancer therapy, lipid nanocapsules (LNCs) have emerged as a viable approach to enhance the bioavailability of poorly soluble pharmaceuticals due to their beneficial properties. This research intends to develop niclosamide-loaded lipid nanocapsules (NIC-LNCs) using the phase inversion technique, followed by the optimization of these formulations via the Box-Behnken experimental design.

A reverse-phase high-performance liquid chromatography (RP-HPLC) method was devised and validated for quantifying niclosamide in the LNC formulations. Optimal chromatographic separation was attained utilizing an Agilent Eclipse XDB-C18 column (150×4.6 mm, 5 µm i.d.) with a mobile phase of a 50:50 (v/v) mixture of acetonitrile and 0.1% H3PO4 phosphate buffer, at a flow rate of 1.2 mL/min. The detection wavelength was set at 335 nm, and the analysis was performed at 35°C. The developed analytical methodology was validated through a comprehensive evaluation of accuracy, linearity, precision, limit of detection, limit of quantitation, specificity, and stability.

The optimization of the NIC-LNC formulation through the Box-Behnken design resulted in an optimal formulation labeled LNC5, consisting of 4% niclosamide, 20% lipid, and 20% surfactant. The proven RP-HPLC method enables accurate quantification of NIC in the LNC formulations. The refined NIC-LNC formulation exhibited developed attributes as assessed by the design.

NIC-LNCs were successfully prepared with particle sizes below 100 nm, narrow size distributions (PDI<0.2), and negative zeta potential values in accordance with the literature. All formulations exhibited high encapsulation efficiency and sustained drug release profiles. The optimum formulation revealed a particle size of 43.29 ± 0.32 nm, encapsulation efficiency of 99.99 ± 0.02%, and drug release at one week of 68.85 ± 1.76%. The formulation maintained stability throughout the short-term study period.

The findings indicate that LNC systems are a promising method for drug administration, especially for anticancer drugs with limited solubility in water.

Pharmacological studies in vitro demonstrate the preventive and therapeutic potential of green tea and its constituent epigallocatechin-3-gallate (EGCG) in the fight against coronavirus disease 2019 (COVID-19). Previously reported correlations between per capita green tea consumption and COVID-19 morbidity/mortality suggest similar effects in vivo. Considering that some recent SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) sub-variants are less influenced by EGCG, this study aimed to determine whether this affects the aforementioned correlations, focusing on comparisons between the periods before (2021) and after (2022-2024) the emergence of the Omicron variant.

Correlations between per capita green tea consumption and COVID-19 morbidity/mortality were calculated using multiple regression models accounting for several confounding factors in a subset (n=84) of countries/territories worldwide with Human Development Index (HDI) above 0.55.

Higher per capita green tea consumption was associated with lower COVID-19 morbidity and mortality. Statistically significant correlations were observed in 2021-2024. Compared with 2021, the strength of both correlations decreased; the relative decrease in the strength of the correlation between per capita green tea consumption and COVID-19 mortality was notably less pronounced.

This differential decrease at the epidemiological level supports the idea that green tea consumption may have not only preventive but also therapeutic value regarding COVID-19. This aligns with in vitro pharmacological evidence indicating that green tea constituents target distinct molecular pathways responsible for the entry of the virus and its replication.

While promising, these findings require further assessment in observational and interventional studies focused on potential therapeutic benefits.

Ovarian cancer (OC) is a malignancy of the female reproductive system for which cisplatin chemotherapy is one of the first-line treatments. Despite the initial response to chemotherapy, such patients eventually develop resistance, which poses a major obstacle to treatment, along with potential side effects. Phytochemicals function as chemosensitizers, offering novel therapies in OC patients by targeting drug resistance, and are perceived to be less toxic. Plumbagin has emerged as an anticancer compound, with some findings suggesting its anti-ovarian cancer activity. However, there is no study on the potential of plumbagin to target cisplatin resistance in non-high-grade OC. The current study aimed to determine the antitumor activity of plumbagin for cisplatin resistance in OC cells in vitro, and to identify its potential molecular target for therapeutic benefit using in silico studies.

Plumbagin was used for in vitro cytotoxic effects on cisplatin-resistant (A2780-CR) and sensitive (A2780-CS) isogenic cell lines using a crystal violet cell viability assay. The binding of plumbagin to the nine selected molecular targets was estimated by molecular docking and their binding energies were compared. The stabilities of the selected docked complexes were confirmed by molecular dynamics simulation (MDS) and molecular mechanics generalized born surface area (MM-GBSA) calculations, and conclusions were drawn to predict the inhibition potential of plumbagin to its best targets.

Plumbagin demonstrated the potential to kill A2780-CR cells, and, expectedly, the cell death effect on A2780-CS ovarian cancer cells demonstrated its anti-tumor activity in vitro. It was found to be non-effective in killing normal non-tumorigenic RPE cells, even at higher doses. Docking analysis suggested that it potentially inhibits through various pharmacological targets with high affinity for binding to Chk1 (PDB ID=1ia8) and Aurora Kinase (PDB ID=5ORL). Molecular dynamic simulation data revealed strong and stable protein-ligand complex formation, which was measured in terms of root mean square deviation (RMSD), root mean square fluctuation (RMSF), and radius of gyration (Rg). On the other hand, the MM-GBSA study revealed that the binding free energy of the CT1019-1ia8 complex (-84.26 ± 2.99 Kcal/mol) and CT1019-5ORL (-67.04 ± 2.63 Kcal/mol) was better when compared to other complexes.

Plumbagin showed anti-ovarian cancer benefits in cisplatin-resistant ovarian cells, and the potential pharmacological targets identified were Chk1 and Aurora kinase.

Our study offers promising insights into plumbagin, particularly in combating cisplatin-resistance OC. However, further in vivo and mechanistic studies are required to validate plumbagin's potential as a therapeutic candidate for OC treatment.

Ibrutinib is a selective tyrosine kinase inhibitor used to treat chronic lymphocytic leukemia (CLL). However, it has low oral bioavailability (2.9%), which is attributed to low solubility (0.002 mg/mL) and a first-pass effect. Ibrutinib-loaded nanostructured lipid carriers (IBR-NLCs) were prepared and investigated in this study to overcome the solubility and presystemic metabolism issues. The goal of the current study was to formulate IBR-NLCs for enhanced bioavailability. IBR-NLCs were optimized using a 3² factorial design and evaluated using various in vitro and in vivo parameters.

IBR interaction with solid lipid (Glyceryl monostearate) and liquid lipid (oleic acid) was studied using molecular docking. The hot-melt ultrasonication method was used to formulate IBR-NLCs, and a 3² factorial design was used for optimization. Particle size, PDI, zeta potential, entrapment efficiency, DSC, XRD, FTIR, SEM, and in vitro study were used to evaluate the NLCs. HepG2 cell lines were used to study the in vitro cytotoxicity of IBR-NLCs and IBR suspension. IBR-NLCs were administered to male Wistar rats in the presence and absence of cycloheximide (CXI) to compare pharmacokinetic parameters.

Molecular docking confirmed good interaction between IBR-GMS and IBR-oleic acid. The optimized IBR-NLCs exhibited particle sizes, PDI, zeta potentials, and %EE of 154.5 ± 0.7 nm, 0.2 ± 0.0, -25.8 ± 1.1 mV, and 84.0 ± 1.2%, respectively. Differential Scanning Calorimetry (DSC) reveals the development of molecular dispersion of IBR in the melted lipid matrix, and X-Ray Diffraction (XRD) studies show a decline in the crystalline drug peaks in the formulation's diffractogram. SEM images showed uniformity distributed spherical-shaped particles. According to an in vitro investigation, IBR-NLCs exhibited a sustained release pattern of 98.0 ± 0.5% with a Korsmeyer-Peppas model mechanism (R² = 0.9615). The IC50 values of IBR suspension and IBR-NLCs were 4.155 µg/mL and 3.03 µg/mL. The AUC0-24 of IBR-NLCs administered in the absence of CXI was 1.60 times higher than the AUC0-24 values in the presence of CXI, indicating lymphatic transport.

IBR-NLCs appear to be promising as a novel innovative nanocarrier for the management of CLL.

Ovarian cancer (OC) is a common malignant tumor of the female reproductive system and is usually found at an advanced stage. However, the treatment of OC with conventional the efficacy of surgery and chemotherapy is limited. Brusatol (BRU) is a unique nuclear factor erythroid 2-related factor 2 (Nrf2) pathway inhibitor with significant anti-cancer effects. At the same time, the Nrf2 system also plays a vital role in ferroptosis, which can be used as a new way to treat tumors. This study investigated the mechanism of action of BRU as a novel ferroptosis inducer to inhibit OC cells.

Using bioinformatics to screen for key targets and pathways that act on OC in BRU, and then the effects of BRU on OC cells were examined by cell viability assay, clone formation assay, wound healing assay, and apoptosis assay. The intracellular levels of ROS (Reactive Oxygen Species), Fe²⁺, glutathione (GSH), and malondialdehyde (MDA) were also quantified. Western blotting analysis was then performed to verify ferroptosis marker proteins and pathways. In addition, the combination of Ferrostatin-1 (Fer-1) and BRU was further tested for ferroptosis-related markers.

By obtaining BRU and OC targets, 171 potential BRU-OC action targets were screened to the core target NQO1. KEGG enrichment analysis showed that the anticancer effects of IBC were mediated through multiple pathways, including the PI3K-AKT and Ras signaling pathways. In vitro results showed that IBC inhibited the proliferation, invasion, and migration of OC cells and induced ferroptosis in OC cells.

We demonstrated that BRU increased intracellular ROS, Fe^2+, and MDA levels. It also significantly reduced intracellular GSH level and the expression of two marker proteins for ferroptosis, GPX4 and SLC7A11. Meanwhile, BRU could inhibit the Nrf2/HO-1/NQO1 and AKT/mTOR dual signaling pathways in OC cells. Furthermore, the combination of Ferrostatin-1 (Fer-1) and BRU reversed BRU-induced ferroptosis in OC cells.

In this study, we demonstrated for the first time through bioinformatics, molecular docking technology, and experimental validation that BRU acts as a novel inducer of ferroptosis in ovarian cancer cells by targeting the Nrf2/HO-1/NQO1 and AKT/mTOR dual signaling pathways, and may have great potential in the treatment of ovarian cancer cells.

Crizotinib, an inhibitor of the epidermal growth factor receptor (EGFR) tyrosine kinase, holds significant potential for the treatment of lung cancer. However, its toxicities present a major challenge to its clinical use. To enhance the targeted delivery of Crizotinib to lung tumors, polymeric-based nanoparticles were developed.

Crizotinib-loaded polymeric nanoparticles were prepared using a nano-precipitation method, incorporating stearic acid as the lipid, polyethylene glycol as the polymer, and Tween 80 as the surfactant. Key formulation parameters were optimized to achieve high-quality nanoparticles.

The optimized formulation exhibited a mean particle size of 142 nm, a zeta potential of -31.9 mV, an entrapment efficiency of 82.35%, and an in vitro drug release of 60.69%. These nanoparticles were then tested on lung cancer cell lines to assess their cytotoxicity, apoptosis induction, and anti-proliferative effects on the cell cycle. In vitro studies confirmed that the Crizotinib-loaded nanoparticles exerted targeted effects on non-small cell lung carcinoma (NSCLC) cell lines, showing maximum inhibitory effects. One year of storage at 4°C, stability testing demonstrated that the lyophilized nanoparticles maintained their effectiveness.

crizotinib nano-formulations were assessed for a variety of physicochemical and in vitro characterization. Five different formulations were designed and optimized on the basis of Particle size, Zeta potential, %EE, and in vitro drug release. Optimum formulation also showed maximum inhibitory effect on the cancer cell line.

This nanotechnology approach offers a promising targeted drug delivery system for Crizotinib, characterized by small particle size, high encapsulation efficiency (EE), and optimal in vitro drug release.

Cholesterol is considered a major factor contributing to cardiovascular diseases. Statins, the most commonly prescribed cholesterol-lowering drugs, are known to have various limitations. Inhibition of Adenosine Triphosphate-Citrate Lyase (ACLY) has been proposed as an alternative therapeutic strategy for managing hypercholesterolemia by lowering cholesterol levels. This has led to the discovery of a cell-permeable small molecule ACLY inhibitor.

ACLY enzyme activity was assessed using an ACLY Assay Kit with the ADP-Glo Kinase Assay Kit. HepG2 cells were treated with test compounds to demonstrate cholesterol and fatty acid synthesis. Pharmacokinetic studies were performed on CD-1 mice following a single oral dose of the compounds. Hypercholesterolemia was induced in mice through a High-Fat and High Cholesterol Diet (HFHCD), and drugs were administered orally for six weeks. Serum and hepatic lipid profiles were subsequently analyzed.

To increase the pharmacochemical properties, four analogues of BMS-303141, ID0018, ID0023, ID0085, and ID0106, were designed and synthesized. These compounds showed superior ACLY inhibitory activity and dose-dependent suppression of cholesterol and fatty acid synthesis in HepG2 cells. Among the analogues, ID0085 exhibited the most potent ACLY inhibition (IC50: 45 nM, 10-fold lower than BMS-303141) and achieved near-complete suppression in cholesterol and fatty acid synthesis at the highest concentration. Pharmacokinetic studies revealed improved half-lives and systemic exposures for all analogues. 
In hypercholesterolemic mouse models, test compounds significantly reduced serum total cholesterol 
(32.0-57.3%) and low-density lipoprotein cholesterol (67.5-80.2%) levels compared to the vehicle group. Notably, ID0085 also increased high-density lipoprotein cholesterol levels.

Among the synthesized analogues, ID0085 exhibited the most potent ACLY inhibition, superior pharmacokinetic properties, and significant improvements in both serum and hepatic cholesterol profiles compared to BMS-303141.

Based on the results, ID0085 appears to be the most promising therapeutic candidate for the treatment of hypercholesterolemia.

Genetic factors play a significant role in the development of leukemia. The overexpression of MDM2 is associated with the progression of certain leukemias. This meta-analysis investigates the relationship between the MDM2 SNP 309T>G and various forms of leukemia across global populations.

A comprehensive literature search was conducted to retrieve genotyping data from twenty case-control studies related to MDM2 SNP 309T>G polymorphism and leukemia. A random-effects model was used to calculate the pooled odds ratio (OR) and 95% confidence interval (95% CI) for the association analysis. MetaGenyo software was utilized to conduct statistical analyses in this meta-analysis.

The findings indicate a significant association between MDM2 309 SNPT>G polymorphism and leukemia in Asian and Caucasian populations. Additionally, this polymorphism is associated with an increased risk of Acute Myeloid Leukemia (AML) and Chronic Myeloid Leukemia (CML), implying that MDM2 may play a role in the pathogenesis of these specific forms of leukemia.

This meta-analysis suggests that MDM2 may represent a susceptibility gene for leukemia risk.