Current Pharmaceutical Design - Online First

The marine ecosystem, known for its diverse biochemistry and organisms adapted to harsh environments, contains numerous plants with promising anticancer potential. Halodule uninervis, a seagrass, contains a variety of bioactive compounds that provide various pharmacological properties. However, its potential anticancer effects against breast cancer remain largely unexplored.

HRLC-MS analysis was conducted to identify the phytochemicals in the ethanolic extract of H. uninervis leaves. Several publicly available databases, including SEA, STP, MALACARDS, DISGENET, and OMIM, were used to identify target genes. Protein-protein interaction (PPI) networks, gene ontology, and pathway analysis were carried out through the STRING and DAVID databases. Molecular docking was performed by Autodock Vina, while molecular dynamics (MD) simulations and MMPBSA analyses were conducted using GROMACS, demonstrating the stability of the complexes up to 200 ns.

The top five therapeutically active phytochemicals were Quercetin, Arborinine, Methyl 3,4,5-trimethoxycinnamate, Citreorosein, and Scopolin. The five hub genes, AKT1, EGFR, TNF, ESR1, and GAPDH, were found by network analyses. Molecular docking and MD simulation demonstrate that Quercetin and Citreorosein are the best phytochemicals exhibiting the highest affinities to breast cancer targets AKT1, EGFR, and ESR1.

For the first time, this in-silico study investigates the potential of citreorosein and quercetin, two phytochemicals predominantly found in H. uninervis leaves, to inhibit the activity of AKT1, EGFR, and ESR1. However, as these results are based on predictive computational analyses, further experimental validation is necessary to confirm their precise mechanisms of action.

Phytochemicals, namely Quercetin and Citreorosein, may have an impact on the progression of breast cancer by binding to the key targets AKT1, ESR1, and EGFR.

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.

Glioblastoma Multiforme (GBM) is a highly aggressive and fatal brain malignancy, with Temozolomide (TMZ) serving as the first-line chemotherapeutic treatment. However, over 50% of patients do not respond to TMZ, and the underlying mechanisms remain unclear. This study utilized the GeCKO library to identify novel genes involved in TMZ resistance and to explore their functions.

Loss-of-function genes related to TMZ resistance in GBM cells were identified using the GeCKO library and Next-Generation Sequencing (NGS), validated by qPCR and CCK-8 assays. CD99L2 function was assessed through proliferation, migration, and EdU assays in U251 and U87 cells. Tumor samples from 55 stage IV GBM patients were analyzed to explore the correlation between CD99L2 expression and Progression-Free Survival (PFS).

GeCKO library screening identified seven genes associated with TMZ resistance. After validation, CD99L2 was confirmed as a key contributor to TMZ resistance. Knockdown of CD99L2 increased the IC50 of U251 and U87 cells by 1.39- and 1.54-fold, respectively. Conversely, CD99L2 overexpression reduced the IC50 by 0.52- and 0.58-fold. CD99L2 knockdown also promoted tumor proliferation and aggressiveness. Additionally, higher CD99L2 expression was associated with longer PFS in GBM patients (median PFS: 7.87 months vs. 2.7 months, P=0.0003).

The functions of CD99L2 remain poorly understood. A few studies have reported that CD99L2 may serve as an adhesion molecule modulating inflammatory responses. One study has shown that CD99L2 is highly expressed in the brain and affects neuronal excitability. These findings suggest that CD99L2 may play a positive role in the body’s defense against glioma.

This study demonstrated that CD99L2 knockdown promotes TMZ resistance and tumorigenesis in GBM, suggesting its potential as a novel biomarker for TMZ resistance.

Impaired intestinal immune function is commonly observed in neonates with intrauterine growth retardation (IUGR), yet its underlying mechanisms and regulatory pathways remain poorly understood. Therefore, we aimed to investigate gene regulatory patterns and microbiota alterations in IUGR piglets.

Three newborn IUGR piglets and three normal littermates were selected from the same sow and sacrificed at seven days of age. Ileal digesta was collected for 16S rRNA amplicon sequencing (16S-seq), and ileum segments were dissociated for single-cell RNA sequencing (scRNA-seq).

The scRNA-seq results revealed a reduced proportion of plasma B cells in IUGR piglets, along with alterations in the distribution of various T cell subsets. KEGG pathway analysis further indicated a downregulation of the B cell receptor signaling pathway in B cells from IUGR piglets. In contrast, both the T cell receptor signaling pathway and antigen processing and presentation were attenuated in T cells. Pseudotime trajectory analysis suggested that the differentiation of B cells was impaired in IUGR piglets. SCENIC analysis revealed that GATA3, IRF2, and BCL11A were downregulated in T cells of IUGR piglets. The 16S-seq results revealed that α-diversity was lower in IUGR piglets. At the genus level, the relative abundance of Prevotella was significantly lower in IUGR piglets.

Significant changes were identified in the proportions of B and T cells, their associated signaling pathways, and intestinal microbiota composition in IUGR piglets, suggesting underlying immune dysfunction and dysbiosis.

We identified novel immune-related transcription factors and key microbes as potential therapeutic targets, shedding light on strategies for preventing and treating IUGR.

Parkinson’s disease (PD) is characterized by the degeneration of dopaminergic neurons within the substantia nigra, leading to progressive motor dysfunction. There are still limited disease-modifying options that counteract the process of disease progression. This study aimed to evaluate the neuroprotective effects of thymol, both in its free form and when loaded onto selenium nanoparticles (SeNPs), in a 6-hydroxydopamine (6-OHDA)-induced PD model using SH-SY5Y cells.

SeNPs were synthesized using a chemical reduction method with ascorbic acid, achieving a 68% entrapment efficiency for thymol. FTIR analysis suggested an interaction between thymol and selenium, which was confirmed by EDX analysis. Nano-Se-thymol particles were observed to be spherical, with a mean size of 135.7 nm and a negative surface charge.

Nano-Se-thymol exhibited low toxicity in normal fibroblast cells and demonstrated greater neuroprotective effects against 6-OHDA-induced cytotoxicity compared to thymol. Nano-Se-thymol significantly reduced ROS generation and increased cell viability compared to 6-OHDA. Furthermore, Nano-Se-thymol decreased the expression of NF-κB inflammatory markers and caspase-3 apoptotic proteins, which were elevated by 6-OHDA, compared to thymol alone.

Nano-Se-Thymol significantly attenuates 6-OHDA-induced cytotoxicity in an established in vitro model of PD. The neuroprotective efficacy of Nano-Se-Thymol is attributed to its enhanced antioxidant capacity, as evidenced by a significant reduction in ROS levels, along with its ability to inhibit apoptosis and modulate cell cycle progression.

Nano-Se-thymol is a potential disease-modifying agent for the treatment of PD; however, further studies and long-term safety assessments are essential to confirm these benefits and understand the underlying mechanisms.

The aim of the study was to prepare polyelectrolyte complex stabilized piperine adjuvant simvastatin nanoformulations and evaluate the antimicrobial effect. Simvastatin has antimicrobial properties but low therapeutic efficacy due to rapid metabolism, with only 12% oral bioavailability. Piperine, a CYP3A4 inhibitor, enhances bioavailability by inhibiting drug-metabolizing enzymes. This study developed chitosan-neem gum polyelectrolyte complex (Ch-NG PEC) nanoparticles combining piperine and simvastatin and evaluated their antimicrobial efficacy compared to simvastatin alone.

A flower-shaped nanoparticles of piperine adjuvant simvastatin were prepared by using chitosan (Ch)-neem gum (NG) as a polyelectrolyte complex (PEC) forming agent, and the anti-microbial effect of nanoformulations with and without piperine was evaluated. A solvent-anti-solvent method was used to form the nanoparticles, and a 3²-factorial design was employed to analyze the impact of chitosan and neem gum concentration on the size of the nanoparticles and entrapment efficiency of simvastatin and piperine followed by their release profile and kinetics.

Nanoparticles showed high drug entrapment efficiency (simvastatin: 96.4-99.7%, piperine: 64.8-99.4%) with sizes ranging from 341.3-629.1 nm. Drug release exceeded 50% in 3 hours and 99% in 8 hours, following Hixon-Crowell and Baker’s Lonsdale models. Antimicrobial assays revealed activity against Staphylococcus aureus but not Candida albicans. The results of the anti-microbial assay indicated that the PEC-based NPs stabilized piperine adjuvant simvastatin showed anti-microbial activity against Staphylococcus aureus but did not exhibit anti-fungal activity against Candida albicans.

Piperine-adjuvant simvastatin Ch-NG-PEC nanoparticles demonstrate potential as a dual-treatment agent for hypercholesterolemia and bacterial infections.

Rheumatoid arthritis (RA) is a chronic inflammatory condition of the joints and a leading cause of global disability. However, the use of current anti-inflammatory treatments is often limited by serious side effects and multi-organ toxicity, necessitating the exploration of safer alternatives.

This study aims to investigate the anti-rheumatic potential of natural compounds of Cassia angustifolia as small-molecule inhibitors of PTGS2.

The therapeutic potential of C. angustifolia was evaluated through antioxidant and anti-inflammatory assays. Gas chromatography-mass spectrometry (GC-MS) was used to identify its constituents. ADMET profiling (absorption, distribution, metabolism, excretion, and toxicity), network pharmacology, and molecular dynamics simulation were employed to uncover the active compounds against PTGS2 for RA treatment.

C. angustifolia extract contained significant phenolic (18.2 ± 0.008 mg GAE/g DW) and flavonoid (27.57 ± 0.03 mg RE/g DW) content. GC-MS yielded 288 compounds of which four passed the toxicity parameters. Protein-protein interaction analysis revealed 10 RA-related targets, with PTGS2 emerging as the most prominent one. Molecular docking and simulations revealed that compound-2 [2-Benzo [1,3] dioxol-5-yl-8-methoxy-3-nitro-2H-chromene] and compound-4 [alpha-hydroxy-N-[2-methoxyphenyl]-benzene propanamide] binds strongly with PTGS2 (-7.7 kcal/mol and -7.9 kcal/mol, respectively) predicting its stable interaction.

C. angustifolia compounds present a significant potential as PTGS2 inhibitors, warranting further in vitro and in vivo investigations to confirm their therapeutic efficacy against RA.

Sorafenib is a first-line treatment for patients with advanced hepatocellular carcinoma (HCC), but its clinical efficacy is often compromised by the acquisition of drug resistance. Various cancers, including HCC, are affected by long non-coding RNA (lncRNA), but the mechanisms underlying HCC sorafenib resistance have not been extensively studied. This article aims to summarize the recently reported pathways associated with sorafenib resistance and discusses potential applications for the treatment of HCC.

Relevant studies on the resistance of HCC to anti-tumor drugs were retrieved from PubMed. Given the compelling evidence that sorafenib is an effective treatment for advanced HCC, we analyzed the research papers on lncRNA and sorafenib resistance in HCC in the PubMed system in the past decade and found that lncRNA may be involved in sorafenib resistance in HCC through multiple pathways.

lncRNA is widely involved in the resistance mechanism of HCC to sorafenib. Recent studies have revealed that numerous lncRNAs, such as NEAT1, affect the sensitivity of HCC to sorafenib through various mechanisms, including autophagy and AKT signaling pathways.

lncRNAs play a pivotal role in modulating HCC resistance to sorafenib. And lncRNA is expected to become a new solution to the resistance of sorafenib and other targeted drugs.

Bear bile powder (BBP) has been traditionally used in Chinese medicine for calming the liver, pacifying the mind, and relieving convulsions, as recorded in Ben Jing Feng Yuan and Yu Qiu Yao Jie. Although the antidepressant effects of BBP have been previously reported, the underlying neurological mechanisms have yet to be fully elucidated. This study aimed to investigate the antidepressant effects of BBP on corticosterone (CORT)-induced depression-like behaviors in female mice and to explore the involvement of the BDNF/TrkB/CREB signaling pathway.

Female mice received subcutaneous CORT injections to induce depression-like behaviors, followed by oral administration of BBP at doses of 50, 100, and 200 mg/kg. Behavioral assessments, biochemical analyses, UPLC-MS/MS, immunohistochemistry, and Western blotting were conducted to evaluate antidepressant effects. Additionally, a CORT-induced HT22 cell injury model was established to assess the neuroprotective mechanisms of BBP, with or without the TrkB antagonist K252a, focusing on the BDNF/TrkB/CREB pathway.

BBP significantly alleviated depression-like behaviors in CORT-treated female mice. It restored neurotransmitter levels, reduced neuronal necrosis in the hippocampal CA3 region, increased DCX-positive cells in the dentate gyrus, and activated hippocampal BDNF/TrkB/CREB signaling. In vitro, BBP attenuated CORT-induced apoptosis and promoted proliferation in HT22 cells. Applying K252a confirmed that BBP’s neuroprotective and antidepressant effects were mediated via the BDNF/TrkB/CREB pathway.

These findings suggest that BBP exerts notable antidepressant and neuroprotective effects in female depression models by modulating neurotransmitters and enhancing neurogenesis through the BDNF/TrkB/CREB pathway. Using both in vivo and in vitro models strengthens the evidence for BBP’s mechanism of action. However, further studies involving additional brain regions and upstream regulatory mechanisms are warranted.

BBP effectively alleviates CORT-induced depressive-like behaviors in female mice by restoring neurotransmitter balance, protecting hippocampal neurons, and promoting neurogenesis via the BDNF/TrkB/CREB pathway. These results provide a theoretical basis for the potential application of BBP in managing female depression.

The autoimmune inflammatory disease known as rheumatoid arthritis (RA) has a complicated and poorly understood etiology. Fibroblast-like synoviocytes (FLSs) have tumor-like characteristics in RA, including aggressive growth and heightened activation that leads to the release of pro-inflammatory factors. These processes are essential for the gradual deterioration of joint tissues. Kaempferol, with the chemical formula 3,5,7-trihydroxy-2-(4-hydroxyphenyl)-4H-1-benzopyran-4-one, is found in many different types of plants and plant families. The pharmacological effects of this substance have been well-documented. The benefits of this substance encompass protection for the heart and brain, as well as fighting inflammation, bacteria, cancer, osteoporosis, and allergies. It also has properties that can help with anxiety, pain relief, and hormonal balance. However, its precise function in the management of RA is still unclear.

To investigate the effect of kaempferol on apoptosis in RA FLSs and elucidate the underlying mechanisms.

We used the CCK-8 assay to assess the effects of different kaempferol concentrations on RA FLSs. We also used flow cytometry with Annexin V-FITC/PI staining to analyse cell cycle distribution and quantify apoptotic cells. To verify apoptosis, the TUNEL test was employed. Important proteins associated with apoptosis were verified to be expressed using western blotting. Finally, network pharmacology analysis was used to identify potential kaempferol targets, and their interactions with AKT1, PIK3R1, and HSP90AA1 proteins were studied using molecular docking and molecular dynamics simulations.

Kaempferol treatment significantly increased apoptosis in RA FLSs, up-regulating the pro-apoptotic protein Bax and down-regulating the anti-apoptotic protein Bcl-2. Specifically, kaempferol at 100 and 200 μM increased the apoptosis index to 29.77 ± 6.02% and 55.63 ± 11.05%, respectively, compared to the control. The induction of caspase-9 and caspase-3 cleavage was observed, indicating the activation of the mitochondrial pathway. Kaempferol also inhibited the phosphorylation of PI3K and Akt, with a significant reduction in their activation. Molecular docking studies demonstrated that kaempferol interacted with AKT1, PIK3R1, and HSP90AA1 proteins, with binding energies of -6.51, -4.26, and -6.51 kcal/mol, respectively, suggesting a strong affinity and potential direct impact on these proteins.

Kaempferol induces apoptosis in RA FLSs by inhibiting phosphorylation of the PI3K/Akt signaling pathway, increasing levels of pro-apoptotic proteins, and decreasing levels of anti-apoptotic proteins. Thus, kaempferol, a naturally occurring flavonoid, has great promise in the management of RA.

This research explored the antimicrobial, antifungal, and in vivo anticandidal activities of two herbal extracts: Ocimum basilicum (HEOB) and Ocimum sanctum (HEOS). Additionally, the study analyzed the phytochemical components of these extracts.

To examine the efficacy of HEOB and HEOS extracts in terms of their antimicrobial, antifungal, and anti-candidal activities and analyze their phytochemical composition, antioxidant potential, and immunomodulatory properties in vivo.

Dried flowers and leaves from Ocimum basilicum and Ocimum sanctum were extracted using a cold maceration process with a 1:1 ethanol-water solution. Phytochemical analysis followed established protocols, and the total phenolic and flavonoid contents were measured using colourimetric methods. HPLC was used to determine the concentrations of specific compounds, including rosmarinic acid, rutin, eugenol, and quercetin. Antioxidant activity, specifically nitric oxide (NO) scavenging and antimicrobial properties, was assessed in vitro using the cup plate method. In vivo studies were conducted on immunocompromised mice with systemic candidiasis, treated with plant extracts at 200 and 400 mg/kg or with ketoconazole as a control. Survival rates, tissue histology, and leukocyte counts were evaluated, and statistical analysis was performed using ANOVA.

HEOB and HEOS extracts possess strong antimicrobial and antioxidant activities, largely due to flavonoids such as rutin, quercetin, rosmarinic acid and eugenol. In vivo experiments revealed that both extracts effectively reduced fungal load, increased survival rates, and alleviated immunosuppression in mice with systemic candidiasis. The extracts also exhibited significant immunomodulatory properties by boosting cell-mediated immune responses. At higher concentrations, the antifungal performance of HEOB and HEOS was similar to that of ketoconazole.

HEOB and HEOS exhibited strong antibacterial, antifungal, and anticandidal properties, showing significant effectiveness in treating systemic candidiasis. Their immunomodulatory effects and ability to boost cell-mediated immunity make these extracts promising options for addressing systemic candidiasis, particularly in individuals with weakened immune systems. This research offers valuable insights and sets the stage for future investigations into the treatment of oral and vaginal candidiasis.

Aldose reductase-2 (ALR2) is a key enzyme in the polyol pathway whose overexpression is implicated in several diabetic complications, including neuropathy, nephropathy, retinopathy, and atherosclerotic plaque formation. Under hyperglycemic conditions, the intracellular accumulation of sorbitol and the depletion of NADPH lead to osmotic imbalance and oxidative stress, driven by the formation of reactive oxygen species and advanced glycation end products. Although various ALR2 inhibitors have been developed, their clinical application has been hampered by nonselective inhibition of both ALR2 and the homologous enzyme ALR1.

In this study, we employed a comprehensive in silico approach to evaluate the inhibitory potential of natural compounds from Cynomorium songaricum against ALR2. Our workflow integrated with ADMET, molecular docking with scoring function and glide XP, molecular dynamics (MD) simulations, PCA, FEL, and MM/GBSA. Through this analysis, four natural compounds of C. songaricum (Compound Name: p-Coumaric acid, Vanillic acid, 4-Oxoniobenzoate, and Phloroglucinol) displayed significant bonds formation including hydrogen and hydrophobic bonds with the target protein.

These bonds exhibited the ligand stability. Further, the MD simulation analysis, followed by post-simulation analysis, verified the dynamic stability of these four natural compounds and compared them with the native ligand of the target protein. These natural compounds exhibit particularly stable binding within the ALR2 selectivity pocket, demonstrating an inhibitory effect over ALR1 when compared with the reference inhibitor, Epalrestat.

These promising in silico findings suggest that CID: 8468 and CID: 135 merit further evaluation through in vitro, in vivo, and clinical studies as potential selective inhibitors for the treatment of diabetic complications.

In this study, the causation between serum metabolites and the risk of Diabetic Nephropathy (DN) was investigated by means of a Mendelian Randomization (MR) analysis.

Our data on diabetic nephropathy were obtained from the IEU OpenGWAS Project database, while serum metabolite data originated came from the GWAS summary statistics by Chen et al. The Inverse Variance Weighted (IVW) method was the main analysis approach, with Weighted Median (WME) and MR-Egger regression serving as supplementary approaches to construing the causalities between serum metabolites and the DN risk. In addition to the MR-Egger regression intercept, Cochran's Q test was utilized for sensitivity analysis, with P values used as the metric to assess the results.

In total, 14 SNPs regarding serum metabolites were chosen as Instrumental Variables (IVs). The IVW results indicated that levels of Behenoylcarnitine (C22), Arachidoylcarnitine (C20), and the ratio of

5-methylthioadenosine (MTA) to phosphate exerted a positive causal effect on the DN risk. Conversely, levels of 5-hydroxylysine, Butyrylglycine, 1-stearoyl-glycerophosphocholine (18:0), Isobutyrylglycine, 1-stearoyl-2-oleoyl-GPE (18:0/18:1), N2,N5-diacetylornithine, 2-butenoylglycine, 3-hydroxybutyroylglycine, N-acetyl-isoputreanine, the ratio of Arginine to Ornithine, and the ratio of Aspartate to Mannose exerted a negative impact of causality on the DN risk. By identifying these serum metabolites, high-risk patients can be recognized in the early stages of diabetic nephropathy, enabling preventive measures or delaying its progression. These findings also provide a solid foundation for further research into the underlying etiology of diabetic nephropathy.

The translation of serum metabolites into clinical applications for DN aims to utilize changes in serum metabolites as biomarkers for early diagnosis, thereby monitoring the progression of DN and providing a foundation for personalized treatment. For instance, the development of serum metabolite diagnostic kits could be used for early detection and prevention of DN. Changes in metabolites can help identify different stages of DN.

Triple-negative breast cancer (TNBC) is an aggressive subtype characterized by

the absence of estrogen and progesterone receptors (ER, PR) and low or absent HER2 expression, limiting treatment options. Quercetin, a flavonoid with anti-cancer properties, has the potential to be a therapeutic

intervention.

The study aimed to explore the potential of Quercetin derivatives as therapeutic agents for TNBC using several computational methods.

The study utilized PASS prediction, molecular docking, ADMET prediction, QSAR models, MD simulations, binding free energy, and DFT calculations to evaluate the efficacy of quercetin derivatives.

ADMET analysis confirmed the solubility, non-carcinogenicity, and low toxicity of four quercetin derivatives: LM01, LM02, LM05, and LM10. These derivatives exhibited strong binding affinity against TNBC protein PPAR1, with binding energies of -10.6, -10.7, -11.4, and -10 kcal/mol, respectively. MD simulations confirmed their stability, with consistent RMSD values and favorable RMSF values. Post-simulation calculations and reduced HOMO-LUMO energy gaps further supported their potential as promising candidates.

Our computational findings suggest that quercetin derivatives, particularly LM01, LM02, and LM10, exhibit strong stability and binding affinity, positioning them as promising candidates for TNBC treatment. Further experimental validation is required to confirm their therapeutic potential.

Colon-targeted drug delivery is a crucial area of research aimed at treating local disorders like IBD, including ulcerative colitis and Crohn's disease. By delivering drugs directly to the colon, this approach enhances therapeutic efficacy and minimizes systemic toxicity. Nanoparticles are an effective vehicle for controlled drug delivery, improving treatment outcomes for colon-specific diseases.

The study aimed to develop an oral nanoparticulate formulation of Satranidazole (STZ) using a solvent evaporation technique for colonic targeting and characterize its physicochemical properties, compatibility, and in vitro drug release profile.

Using a modified solvent evaporation method, STZ-loaded nanoparticles (STZ-NPs) were formulated using Eudragit RS100 and RL100 polymers. Preformulation studies, including FT-IR and DSC, were performed to confirm the compatibility between the drug and polymers. The nanoparticles were evaluated in terms of entrapment efficiency, particle size, zeta potential, polydispersity index, and in vitro drug release study.

The optimized formulation (F3) demonstrated the highest entrapment efficiency (83.55%) with particle sizes ranging from 107.9 nm to 302 nm and a zeta potential between -34.25 mV and +48.8 mV. In vitro drug release studies showed controlled release over 16 hours, with the optimized batch achieving 95.85% drug release, indicating effective accumulation in the inflamed colon.

The Satranidazole-loaded nanoparticles, containing time- and pH-dependent polymers, successfully inhibited premature drug release in acidic environments and provided controlled release at colonic pH. Thus, this delivery system shows promise as an effective treatment for IBD, offering targeted drug release and reduced systemic toxicity.

Dysphania ambrosioides, commonly known as “mastruz,” is a medicinal plant traditionally used for its therapeutic properties, including antimicrobial and anti-inflammatory effects. Previous studies have also suggested its antitumor potential. However, its role in oral squamous cell carcinoma (OSCC) remains unexplored. This study aimed to evaluate the in vitro cytotoxic effects of D. ambrosioides extracts on SCC4 (OSCC) and HaCaT (human keratinocyte) cell lines.

Crude extracts were obtained using different methods, including hexanic, ethanolic, hydroethanolic (7:3), and aqueous extractions, all performed ultrasonic-assisted extraction. The extracts were tested at concentrations ranging from 7.81 µg/mL to 1000 µg/mL using 2-fold serial dilutions. Cell viability was assessed after 48 hours of treatment using the MTT assay, with DMSO as the control.

The extracts exhibited concentration-dependent cytotoxic effects on both cell lines, with HaCaT cells showing greater sensitivity. However, the lack of selectivity toward tumor cells over normal cells suggests a broad-spectrum cytotoxic activity without tumor-specific therapeutic targeting.

These findings highlight the need for further fractionation of the extracts and identification of the bioactive compounds responsible for the observed effects. Although the extracts demonstrated significant cytotoxic activity, their therapeutic potential should not be limited to cytotoxicity alone. Future studies should explore additional biological activities, such as anti-inflammatory or immunomodulatory properties, to fully understand the therapeutic applications of D. ambrosioides.

In this study, pure and cobalt manganese-doped ZnO nanoparticles (Zn(1-x-y)MnxCoyO NPs) at varying concentrations were synthesized through sol-gel method, and zinc acetate dihydrate, manganese nitrate, cobalt acetate, and diethyl amine were used as precursors, with samples finally calcined at 700°C.

The hexagonal wurtzite structure of pure and co-doped ZnO NPs was confirmed by X-ray diffraction (XRD). The computed grain sizes of pure and co-doped ZnO NPs, according to Scherrer's formula, were 32 nm, 32.5 nm, 36.3 nm, and 36.5 nm, respectively. Scanning electron microscope (SEM) was used to observe the morphology of nanoparticles. FTIR spectroscopy was used to examine the chemical make-up and vibrational modes of pure and co-doped ZnO NPs. The bandgaps of pure and doped ZnO were examined using UV-Vis spectroscopy.

It was found that the optical bandgap of ZnO was lowered by 3.21 eV by manganese and cobalt doping. Elemental composition analysis was performed by using EDX analysis. Finally, anticancer activity of pure and co-doped ZnO NPs was assessed by employing MTT assay, which indicated that Zn0.8 Mn0.1 Co0.1O NPs showed significant anticancer results against liver cancer (HepG2) cells as compared to ZnO, Zn0.98 Mn0.01Co0.01O and Zn0.90 Mn0.05 Co0.05O NPs. Moreover, Zn0.8 Mn0.1 Co0.1O NPs showed low toxicity and good biocompatibility comparable to doxorubicin (DOX).

Comprehensive experimental findings have demonstrated an authentic way of obtaining feasible in vivo liver cancer therapy.