Skip to content
2000

Current Pharmaceutical Design - Volume 31, Issue 12, 2025

Volume 31, Issue 12

Volume 31, Issue 12, 2025

    • Immunotherapy for Type 1 Diabetes: Mechanistic Insights and Impact of Delivery Systems

      https://doi.org/10.2174/0113816128343081241030054303

      Type 1 diabetes is an autoimmune disease characterized by the destruction of insulin-producing pancreatic β-cells, leading to hyperglycemia and various complications. Despite insulin replacement therapy, there is a need for therapies targeting the underlying autoimmune response. This review aims to explore the mechanistic insights into T1D pathogenesis and the impact of delivery systems on immunotherapy. Genetic predisposition and environmental factors contribute to T1D development, triggering an immune-mediated attack on β-cells. T cells, particularly CD4+ and CD8+ T cells, play a central role in β-cell destruction. Antigen-specific immunotherapy is a unique way to modify the immune system by targeting specific antigens (substances that trigger the immune system) for immunotherapy. It aims to restore immune tolerance by targeting autoantigens associated with T1D. Nanoparticle-based delivery systems offer precise antigen delivery, promoting immune tolerance induction. Various studies have demonstrated the efficacy of nanoparticle-mediated delivery of autoantigens and immunomodulatory agents in preclinical models, and several patents have been made in T1D. Combining antigen-specific immunotherapy with β-cell regeneration strategies presents a promising approach for T1D treatment. However, challenges remain in optimizing delivery systems for targeted immune modulation while ensuring safety and efficacy.

    • Antibiotic Exposure and Childhood Overweight/Obesity: Evidence from Epidemiological and Experimental Studies

      https://doi.org/10.2174/0113816128333496240911061551

      Childhood overweight and obesity are nutritional disorders in which children's energy intake exceeds energy consumption for a long period, resulting in the excessive accumulation of body fat and weight that exceeds a certain range. It is one of the most serious public health issues. In recent years, its prevalence has shown a significant upward trend, and 41-80% of childhood obesity can persist into adulthood. Scholars are now more interested in researching this further. Since antibiotics have been used extensively since their discovery, more focus has been paid to the possible risks these medications pose to children who are exposed to them. Recently, some studies have explored the possible link between antibiotic exposure and the prevalence of overweight and obesity in children. However, their findings are inconsistent. Therefore, this review aims to synthesize and summarize the studies related to the effects of antibiotics on childhood obesity, elucidate the possible associations between the two, and provide an in-depth discussion of the potential biological mechanisms by which antibiotics exposure may contribute to childhood obesity.

    • Understanding and using Animal Models of Hepatotoxicity

      https://doi.org/10.2174/0113816128338726241029175250

      Hepatotoxicity is a critical health hazard, primarily contributing to the increased incidence of deaths globally. The liver is one of the major and extremely vital organs of the human body. Autoimmune diseases, viruses, exposure to toxicants such as carcinogens, and changes in eating habits can all cause liver problems, among other things. Free radical generation, together with raised enzyme levels including SGOT, SGPT, and total bilirubin, are among the pathological changes set off by liver injury. Hepatotoxicity causes changes in cells, such as eosinophilic cytoplasm, nuclear pyknosis, fatty degeneration, too many liver lesions, and hepatic centrilobular necrosis due to lipid peroxidation. Researchers have used animal models to investigate liver diseases and toxicities. Drugs such as azathioprine, alcoholism, paracetamol intoxication, and anti-tuberculosis drugs are some of the most common causes of liver toxicity. These toxins cause calcium ions (Ca2+), reactive oxygen species (ROS), and inflammatory mediators to be released inside cells. This activates immune cells like NK cells, NKT cells, and Kupffer cells. These signaling pathways also play roles in hepatotoxicity. Due to its pathogenesis, no effective drug is currently available for hepatotoxicity due to a lack of understanding related to the signaling factors involved in it. The paper primarily examines different experimental models of hepatotoxicity, including non-invasive and invasive methods, as well as genetic models. As such, these models are crucial tools in advancing our understanding of hepatotoxicity, thus paving the way for new therapeutic interventions.

    • Design, Synthesis, and Molecular Docking of Quinazolines Bearing Caffeoyl Moiety for Targeting of PGK1/PKM2/STAT3 Signaling Pathway in the Human Breast Cancer

      https://doi.org/10.2174/0113816128337881241016064641
      Background

      PGK1 and PKM2 are glycolytic enzymes, and their expression is upregulated in cancer cells. STAT3 is a transcription factor implicated in breast cancer progression and chemoresistance. Researchers worldwide continue to explore how targeting genes might lead to more effective anti-breast cancer therapies. The present study aims to synthesize quinazolines containing caffeoyl moiety for developing innovative anticancer agents against the human breast cancer cell line (MCF-7).

      Methods

      A new quinazoline was synthesized by reacting caffeic acid with 5-amino-phenylpyrazole carboxylate in the presence of PCl. Compound reacted with NHNH.HO to produce compound through cyclo-condensation. Apoptosis and necrosis as well as inhibition activity compounds and against PGK1, and PKM2 were evaluated. The effect of compounds and on the levels of GSH, GR, SOD, GPx, CAT, MDA, Bax, Bcl-2, caspase-3, P53 and VEGF levels as well as PGK1, PKM2 and STAT3 gene expression were estimated in MCF-7 tumor cells.

      Results

      The viability of MCF-7 cells was reduced to 22.42% and 45.86% after incubation with compounds and for 48 hours, respectively. The IC values for compounds and are 62.05 µg/mL and 16.73 µg/mL. Furthermore, compound exhibited more significant apoptosis and necrosis than compound . IC values of compound against PGK1, and PKM2 at interval concentration equals 1.04, and 0.32 µM/mL, respectively, after 210 minutes of incubation. Moreover, compound were revealed strong inhibition of PGK1, and PKM2 with IC values equals 0.55 and 0.21 µg/mL, respectively after 210 minutes of incubation. Our results proved that the incubation of compounds and with MCF-7 cells increased the levels of apoptotic proteins, elevated MDA, Bax, caspase-3 and P53 levels, depleted GSH, GR, SOD, GPx, CAT, Bcl-2 levels and down-regulated the levels of STAT3, PGK1, and PKM2 gene expression significantly. Our results proved that compound showed a stronger estimated binding affinity with a ∆G of -7.2, -7.5, and -7.9 kcal/mol., respectively towards PGK1, PKM2 and STAT3 proteins. Also, compound exhibits a strong binding affinity with ∆G of -7.9, -8.5, and - 8.7 kcal/mol., towards PGK1, PKM2 and STAT3 proteins.

      Conclusion

      The results show that compounds and induce apoptotic activity by blocking the PGK1-PKM2-STAT3 signaling pathway. The present investigation opens exciting possibilities for developing innovative new anticancer quinazolines bearing caffeoyl moiety.

    • Galangin Regulates Astrocyte Phenotypes to Ameliorate Cerebral Ischemia-reperfusion Injury by Inhibiting the RhoA/ROCK/LIMK Pathway

      https://doi.org/10.2174/0113816128322927241015120431
      Purpose

      This study aimed to explore whether Galangin (Gal) could improve cerebral Ischemia- reperfusion (I/R) injury by regulating astrocytes, and clarify its potential molecular mechanism.

      Methods

      An I/R injury model of rats was established using the Middle Cerebral Artery Occlusion/Reperfusion (MCAO/R) method, followed by the administration of Gal (25, 50, 100 mg/kg) gavage for 14 consecutive days. Besides, astrocytes were isolated from the rats to construct an Oxygen-Glucose Deprivation/Re-oxygenation (OGD/R) cell model, with treatments of Gal or the Ras homolog gene family member A (RhoA)/Rho-associated Coiled-coil containing protein Kinase (ROCK) inhibitor Y-27632. Subsequently, the severity of nerve injury was assessed using the modified Neurological Severity Score (mNSS) test; behavioral disorders in I/R rats were observed through the open field and ladder-climbing tests. Pathological damages and neuron survival in the peri-infarct zone were examined by hematoxylin and eosin staining and NeuN staining, respectively. Additionally, immunofluorescence staining was employed to determine astrocyte polarization and TUNEL staining was carried out to measure the level of cell apoptosis; also, western blot was performed to detect the expression of proteins related to the RhoA/ROCK/LIM domain Kinase (LIMK) pathway.

      Results

      Gal significantly ameliorated the neurological and motor dysfunctions caused by I/R in rats, reduced pathological damage in the peri-infarct zone, and promoted neuronal survival. Additionally, Gal increased the number of A2 astrocytes, while it decreased the number of A1 astrocytes. experiments revealed that the effect of Gal was consistent with that of Y-27632. Additionally, Gal significantly enhanced the survival of OGD/R cells, increased the number of A2 astrocytes, and inhibited the expression of proteins associated with the RhoA/ROCK pathway.

      Conclusion

      Gal could reduce the level of apoptosis, promote the polarization of A2 astrocytes, and improve cerebral I/R injury, and its mechanism may be related to the inhibition of the RhoA/ROCK pathway.

    • Bioassay and Pharmacokinetic Characteristics of Plant Extract as Possible Acaricidal Agent

      https://doi.org/10.2174/0113816128317849241108064144
      Background

      Effective management strategies against tick infestations are necessary because tick-borne diseases represent serious hazards to the health of humans and animals worldwide. The aim of this study was to examine the larvicidal and ovicidal properties of extract against a notorious tick species, .

      Methodology

      The maceration method was used to prepare the ethanolic extract of The extract was then used in an adult immersion test (AIT) and larval packet test (LPT) to asses the plant's toxicity. To elucidate the mode of action, molecular modeling and docking studies were conducted. ADMET analysis was then carried out to find out the drug-likeness profiles of the plant phytochemicals.

      Results

      Significant death rates and egg inhibition were found at different extract doses using the larval packet test (LPT) and adult immersion test (AIT). A concentration-dependent impact was observed at a concentration of 40 mg/mL, which resulted in the maximum larval mortality (92 ± 2.646) and egg inhibition (77.057 ± 2.186). Additionally, the potency of the extract against was determined by calculating its fatal concentrations (LC, LC, and LC). A three-dimensional model of the octopamine receptor was created, and docking studies showed that the receptor and possible ligands, most notably Xanthatin and Xanthosin, interacted well. The potential of compounds as tick control agents was highlighted by their pharmacokinetic characteristics and toxicity profiles, as revealed by drug-likeness and ADMET studies. Molecular dynamic simulations further demonstrated the stability of the protein-ligand complex, indicating the consistent association between the ligand and the target protein.

      Conclusion

      Overall, this study provides valuable insights into the potential use of extract and its compounds as larvicidal and ovicidal agents against , paving the way for further research on tick control strategies.

Volumes & issues

82 Ahead of Print Articles

Most Cited Most Cited RSS feed

This is a required field
Please enter a valid email address
Approval was a Success
Invalid data
An Error Occurred
Approval was partially successful, following selected items could not be processed due to error
Please enter a valid_number test