Anaplastic thyroid cancer (ATC) is a highly malignant tumor with poor prognosis and limited therapeutic options, creating an urgent need for novel treatments. This study aimed to investigate the inhibitory effect of Vemurafenib (Ve) combined with Panobinostat (Pa) on human ATC cells (FRO and ARO) and its underlying mechanism. Four groups were established: Control, Ve, Pa, and Ve+Pa. Cell proliferation and drug synergy were analyzed using CCK-8 assay, colony formation assay, and CompuSyn software. Cell migration, invasion, apoptosis, and glucose consumption were detected by Transwell assay, wound healing assay, apoptosis assay, and glucose consumption assay, respectively. Molecular markers were examined via RT-qPCR, Western blotting, and immunofluorescence. CompuSyn analysis verified the synergistic effect of Ve+Pa in FRO and ARO cells. Compared with the other three groups, the Ve+Pa group showed significantly suppressed cell proliferation, migration, invasion, and glucose consumption, as well as enhanced apoptosis. Moreover, the mRNA and protein expression of the sodium iodide symporter (NIS) and iodine metabolism-related molecules was upregulated, whereas glucose transporter 1 (GLUT1) expression was downregulated. Ve combined with Pa exerts a synergistic inhibitory effect on the growth and metastasis of FRO and ARO cells, while promoting apoptosis and cellular redifferentiation. This combination may provide a potential therapeutic strategy for ATC.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder marked by cognitive decline and complex, multi-factorial pathology. Current single-target drugs provide only limited benefits, and there is a need for more effective therapeutic strategies. β-asarone, a major volatile component of Acorus tatarinowii used in traditional Chinese medicine (TCM), has demonstrated neuroprotective effects, including anti-apoptotic, anti-inflammatory, and anti-amyloid β (Aβ) toxicity properties. However, the molecular targets and signaling mechanisms of β-asarone in AD remain underexplored. This study aims to explore the molecular targets and signaling mechanisms of β-asarone in AD by integrating network pharmacology, molecular docking, and molecular dynamics simulations. Network pharmacology was used to identify overlapping targets between β-asarone and AD. Protein-protein interaction networks were constructed using STRING, and key targets were analyzed for enrichment in the PI3K-AKT/MAPK pathways. Molecular docking was conducted to assess the binding affinity of β-asarone with multiple targets along the PI3K-AKT axis. Additionally, molecular dynamics (MD) simulations of the β-asarone-AKT1 complex were performed for 100 ns to assess the stability of the interaction. Seventy-four overlapping targets of β-asarone and AD were identified, with key hub genes enriched in the PI3K-AKT/MAPK pathways. Molecular docking revealed that β-asarone binds to critical nodes along the PI3K-AKT axis with binding free energies (ΔG) of approximately -6.2 kcal/mol and to HRAS/IGF1 with ΔG ≈ -5.2/-4.1 kcal/mol. MD simulations showed stable trajectories for the β-asarone-AKT1 complex (RMSD ~3.5-4.0 Å) with persistent hydrogen bonds, indicating a durable interaction in the ATP-binding pocket. β-asarone interacts with multiple interconnected signaling nodes, particularly the PI3K-AKT pathway, to modulate apoptosis, neuroinflammation, and cellular energetics. These findings support the potential of β-asarone as a TCM-derived candidate for the development of therapeutic strategies for AD.

As a novel nitroimidazole antimicrobial, the quality control of Morinidazole is crucial for ensuring clinical drug safety, particularly in monitoring specific impurities that may arise during production or storage. To establish a method capable of simultaneously quantifying two Morinidazole impurities, three Ornidazole impurities, and one Levornidazole impurity (Levornidazole impurity II), and to evaluate its environmental friendliness. Separation was performed using a Waters Symmetry C18 column with a mobile phase consisting of 0.05 mol/L potassium dihydrogen phosphate buffer (pH 7.0) and acetonitrile in a gradient elution program. The flow rate was 1.0 mL/min, the column temperature was maintained at 30°C, the detection wavelength was set at 319 nm, and the injection volume was 20 µL. Impurity quantification was performed using the main component self-compare method (Quantitative Analysis of Multi-components by a Single Marker, QAMS), and the results were compared with those obtained by the external standard method. Method validation was conducted in accordance with ICH guidelines. The method demonstrated good specificity. The limit of quantification (LOQ) and limit of detection (LOD) were 0.2 µg/mL and 0.06 µg/mL, respectively. Excellent linearity (r ≥ 0.995) was achieved within the range of 0.2-4.0 µg/mL. The average recoveries ranged from 95% to 105% (RSD < 2.0%). Both the system suitability solution and the test sample solution remained stable for 30 hours. The Analytical Greenness (AGREE) and Blue Applicability Grade Index (BAGI) scores for the QAMS method were 0.66 and 80.0, respectively. No significant difference was found between the results obtained by the QAMS method and the external standard method. The established HPLC-QAMS method is accurate, sensitive, and environmentally friendly. It is suitable for the quality control of related impurities in Morinidazole Sodium Chloride Injection and provides technical support for the clinical safety evaluation of this preparation.

Liquidambaris Fructus can play an anti-tumor role by triggering cell cycle blockade and apoptosis and inhibiting cancer cell proliferation. To evaluate the effects and potential mechanism of Liquidambaris Fructus on 143B cells and MNNG/HOS CI #5 cells. Cell viability of 143B cells and MNNG/HOS CI #5 cells was evaluated using the CCK-8 assay. A transwell cell migration assay was performed to detect cell migration and invasion. Cell apoptosis was assayed by flow cytometry. Network pharmacology method was used to predict the potential targets and pathway of Liquidambaris Fructus against osteosarcoma. Protein levels were determined using Western blot, while mRNA levels were detected using RT-qPCR analysis. In vitro efferocytosis assay of apop143B-MHSW and apopMNNG-HMDMs was detected by flow cytometry. Liquidambaris Fructus can effectively increase 143B and MNNG/HOS CI #5 cell apoptosis levels and inhibit 143B and MNNG/HOS CI #5 cell viability, migration and invasion. Network pharmacology showed that PTGS2 and TGFB1 were two targets related to the enriched efferocytosis pathway. Liquidambaris Fructus inhibited proteins and mRNA of PTGS2 and TGFB1 expression levels in 143B and MNNG/HOS CI #5 cells. Liquidambaris Fructus inhibited PTGS2 and TGFB1 levels in the co-culture of osteosarcoma cells and macrophages. Liquidambaris Fructus inhibited efferocytosis. Liquidambaris Fructus can target PTGS2 and TGFB1 to inhibit osteosarcoma cell growth and metastasis, as well as to inhibit efferocytosis, thus alleviating osteosarcoma.

Dry mouth is a condition associated with significant morbidity. It not only causes discomfort but also increases risk of many health and oral health problems. This study compared the efficacy and patient satisfaction of a novel sesame oil wafer, called "Freeze-Dried Sesame Oil Emulsion Salivary Substitute (FD-SOESS)," with ACT® lozenges in managing dry mouth in patients who had undergone treatment for head and neck cancer. A randomized, single-blind, crossover trial was conducted in 35 patients. Subjective dry mouth (Shortening Xerostomia Inventory), objective dry mouth (Clinical Oral Dryness Score, CODS), dysphagia (Eating Assessment Tool-10, EAT-10) and oral mucositis (WHO Oral Toxicity Scale) were assessed before and after 2 weeks of use. Satisfaction was rated using a visual analog scale (VAS 0-10). Outcomes were compared using paired t-tests and Wilcoxon signed-rank tests at a significance level of 0.05. Both products showed significant improvements in objective dry mouth. While the lozenges group showed a borderline significant improvement in subjective dry mouth (P=0.037). Notably, the FD-SOESS group demonstrated significant improvement in dysphagia scores (P=0.003). Satisfaction levels were moderate to high in both groups, with slightly higher levels in the FD-SOESS group. To conclude, FD-SOESS significantly improved objective dry mouth and dysphagia but not subjective dry mouth. It received a relatively high level of satisfaction. Therefore, this newly developed product has the potential to be an alternative product for dry mouth patients.

Application of drugs through the transdermal route is preferable over other routes of drug delivery because of the ease of drug administration and reduced systemic side effects. Mirtazapine is a BCS class II noradrenergic and specific serotonergic drug and shows poor solubility and bioavailability. This study aims to develop and optimize a mirtazapine-loaded lipid-based transethosomal gel to enhance transdermal drug delivery and bypass first-pass metabolism. The current study is an attempt to minimize the systemic side effects associated with oral administration of mirtazapine and to avoid first pass metabolism by administering the drug through the skin. Transethosomes were formulated using the cold method and optimized via Box-Behnken design by varying phospholipid, surfactant, and ethanol concentrations. The optimized formulation (F-16) exhibited high entrapment efficiency (75.92%) and cumulative drug permeation (73.62%) after 6 hours. Multiple characterization tests confirmed nano-sized, stable vesicles with a zeta potential of -34.1 mV and particle size of 479.3 nm. The transethosomal dispersion was incorporated into a Carbopol gel and evaluated for pH, viscosity, spreadability, drug content, and skin permeation. Ex-vivo studies showed enhanced skin permeation from the gel compared to the dispersion. Stability tests confirmed physical integrity over 60 days, while skin irritation and toxicological studies in animal models indicated excellent biocompatibility, with no signs of inflammation or organ toxicity. These findings and the study suggests that the transethosomal gel formulation is a promising and safe approach for transdermal delivery of mirtazapine, potentially improving its bioavailability and therapeutic effectiveness resulting in bypassing first pass metabolism.

Herbs, like Allium sativum, Ginkgo biloba and Nerium oleander are traditional medicinal plants that have been used to treat atherosclerosis and cardiovascular disease. This study provides valuable insights into how network pharmacology (NP) and emerging machine learning are utilized to identify potential drug candidates from these plants for treatment of atherosclerosis. NP analysis was employed to screen compounds and their potential gene targets from databases and tools e.g. IMPPAT, PubChem, KNAPSACK, Swiss ADME, Swiss Target Prediction, Disgenet and GeneCard. Cytoscape 3.10.2 was employed to visually understand these networks. DAVID database was used for functional and enrichment analysis of the genes validated through molecular docking using PyRx and Discovery Studio. Computational tools and bioinformatics approaches showed a few core compounds, such as Quercetin, Naringenin, Luteolin, Kaempferol, Apigenin, Daidzein, Luteolin-7-olate, Pinocembrin, Pregnenolone and Fisetin found to be effective against atherosclerosis. Pathway analysis revealed that mechanism of atherosclerosis development is directly associated with cholesterol metabolism, cellular senescence, Ras, NF-κB and PI3K-Akt signaling pathways. NP and molecular docking analysis suggested that screened compounds may inhibit progression of atherosclerosis by modulating key associated pathways. Hence, this machine learning aided NP study provides basis for understanding and recognizing the activity of these plants in treating atherosclerosis.

Type 2 diabetes involves insulin resistance, where muscle, liver, and fat cells fail to utilize glucose leading to hyperglycemia. This study explores the therapeutic potential of pulegone in type 2 diabetes by examining its molecular interactions with key metabolic targets and evaluating its effects on insulin resistance and inflammatory cytokine modulation. Except for normal controls, animals were fed a high-sucrose, high-fat diet for four months to induce insulin resistance. Treatment groups received metformin (150 mg/kg) or pulegone doses: low (5 mg/kg), medium (10 mg/kg), and high (15 mg/kg) for 45 days. Post-treatment, tissues and blood were collected. Blood serum was analyzed for liver markers, lipid profile, and blood for glycated hemoglobin. ELISA was used for cytokines (resistin, adiponectin, IL-1Ra, TNF-α), and qPCR assessed gene expression of NF-κB, TNF-α, PPAR-α/γ, IL-6, IL-10, IL-1Ra, and adiponectin. Histopathology was performed. Data were analyzed using GraphPad Prism. Molecular docking was conducted to identify the binding affinities of pulegone to target proteins. Pulegone significantly reduced fasting blood glucose, glycated hemoglobin, triglycerides, cholesterol, and liver enzymes, while increasing HDL levels compared with diabetic controls. It also decreased serum resistin, TNF-α, IL-6 and NF-κB expression, while upregulating adiponectin, IL-10, PPAR-α, PPAR-γ and IL-1Ra. Histopathological examination showed protective effects on the pancreas, liver, kidney, heart, and aorta. Docking analysis favored strong binding affinities of pulegone with key targets. Pulegone ameliorates insulin resistance by improving glycemic and lipid profiles, modulating pro- and anti-inflammatory cytokines, and protecting vital organs, suggesting its potential as a multitarget antidiabetic agent.

Impaired glucose tolerance (IGT) is a reversible pre-diabetic condition characterized by early disruptions in insulin resistance and glucose control. Wingless-type MMTV integration site family member 5a/ secreted frizzled-related protein 5 (Wnt5a/Sfrp5) signaling and GLP-1 modulation have been identified as possible treatment approaches. The effects of low-intensity aerobic activity, Huatuo Five-animal Play exercise and bifidobacterium triple viable capsules on glucose-lipid metabolism and GLP-1/Wnt5a/Sfrp5 signaling were assessed in this randomized, parallel-group clinical trial involving ninety persons with IGT. The designated intervention was given to participants for four weeks. Before and during therapy, measurements were taken of fasting blood glucose (FBG), 2 h post-load glucose (2hFBG), glycosylated hemoglobin (HbA1c), fasting insulin, homeostasis model assessment of insulin resistance (HOMA-IR), serum lipids and circulating GLP-1, Wnt5a and Sfrp5. All treatments improved lipid indices, characterized by reductions in total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C), along with an increase in high-density lipoprotein cholesterol (HDL-C) and significantly lowered FBG, 2hFBG, HbA1c, fasting insulin and HOMA-IR (P<0.05). Compared with aerobic exercise, Five-animal Play generated higher decreases in FBG, 2hFBG and HOMA-IR and a more significant decline in Wnt5a (P<0.05). Outcomes in the Five-animal Play group were comparable to the probiotic group. There were no negative responses or toxicities to the kidneys or liver. Huatuo Five-animal Play may offer a safe, mechanism-based non-pharmacological approach for early metabolic intervention in pre-diabetes.

Diabetes mellitus (DM) is a long-term metabolic disorder that poses a significant challenge to healthcare systems worldwide and is considered one of the top five leading causes of death globally. The current study was designed to evaluate the two newly synthesized thiobarbituric acid analogues for anti-hyperglycemic potential. In experimental animal diabetes was induced using alloxan. The compounds designated as SL1 and SL2 were fed to animals to ameliorate the symptoms of induced diabetes. Level of blood glucose and weight of animals along with other biochemical parameters were monitored daily for four weeks. Antioxidant enzymes catalase, superoxide dismutase and malondialdehyde (MDA) levels were also evaluated. Safety profile of compounds SL1 and SL2 was confirmed up to 250 mg/kg. Groups treated with SL1 had a substantial reduction in blood glucose levels (127.25±4.81mg/dL and 115.61±4.65 mg/dL) at respective doses, whereas for SL2 the recorded values were 148.98±4.36 mg/dL and 129.81±4.59 mg/dL (p<0.001). The diabetic group of animals treated with SL1 and SL2 significantly reduced HbA1c (p<0.001), total cholesterol (p<0.001), low-density lipoprotein (LDL), triglycerides (p<0.001), alkaline phosphatase (ALP), bilirubin and creatinine. Furthermore, the activity of superoxide dismutase (SOD) and catalase (CAT) was effectively enhanced in the treated groups (p<0.001). Both the compounds were significantly effective in normalizing the symptoms of induced diabetes and changes brought about in other blood parameters in experimental animals.