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Current Pharmaceutical Design - Volume 31, Issue 22, 2025

Volume 31, Issue 22

Volume 31, Issue 22, 2025

    • Advancements in Managing Schizophrenia through Classical Approaches, Mechanisms, and Deep Brain Stimulation

      https://doi.org/10.2174/0113816128341348241224065313

      Schizophrenia is a heterogeneous neuropsychological disorder characterized by three distinct sets of symptoms: positive, negative, and cognitive. It carries significant public health implications and is estimated to affect up to 1% of the population. Despite extensive research, the underlying mechanisms of schizophrenia are not entirely understood, and existing antipsychotic treatments have notable limitations. Firstly, these treatments are effective for only approximately half of the patients. Secondly, they primarily alleviate positive symptoms such as misperceptions and thought disorders, which are core to the illness, while neglecting the negative symptoms like flat affect and social withdrawal, as well as cognitive symptoms such as learning and attention difficulties. Thirdly, these treatments come with significant neurofunctional and metabolic side effects, and in some cases, they can lead to issues like sexual dysfunction or agranulocytosis (in the case of Clozapine (CLZ). In this review, we delve into currently available treatments for schizophrenia, with the utilization of Deep brain stimulation techniques to overcome the limitations of antipsychotics. We also discuss the major clinical trials for schizophrenia along with deep brain stimulation intervention.

    • Nucleic Acid-based Therapy in Effective Management of Rheumatoid Arthritis

      https://doi.org/10.2174/0113816128331823241121055205

      Rheumatoid Arthritis (RA) is a chronic autoimmune disease that prominently affects the joints of the body, including one or more types, such as wrists, knees, fingers, and toes. This condition is characterized by specific auto-immune responses, ., inflammation, swelling, stiffness, and pain in the body's joints. This results in partial or complete immobility. Several treatment options are available in the pharmaceutical market, commonly immunosuppressants, anti-inflammatory drugs, corticosteroids, anti-antibody drugs, . However, such drug treatments provide only symptomatic relief and lack long-term therapeutic efficacy. Thus, there is a need to develop an alternative treatment option that potentially can cure this disease. Recently, researchers have shifted their focus to targeting the root cause involved in the pathogenesis of RA by designing nucleic-acid-based molecules. With this objective, we have provided this review in which we have explored the nucleic acid-based techniques used to treat RA. Various molecular and genetic methods, including antisense oligonucleotides, small interfering RNA (siRNA), CRISPR-Cas9 gene editing, RNA-based vaccines, microRNA (miRNA) therapeutics, and epigenetic modifications are used to target the mechanisms underlying RA pathogenesis. Through the extensive evaluation of clinical and preclinical studies, we reported nucleic acid-based therapy's clinical efficacy, safety, and therapeutic benefits. In addition, this study states the associated pharmacokinetic challenges followed by approaches to overcome them. Nucleic acid-based therapies are susceptible to degradation by nucleases in the body and are not efficiently absorbed due to their considerable molecular weight. Specialized carriers like nanoparticles are employed for their effective delivery. Nucleic acid-based therapies hold immense potential for achieving more effective, less toxic, and patient-centric management of RA, offering hope for improved outcomes and an enhanced quality of life for individuals living with this challenging autoimmune condition.

    • Cancer Drug Targeting: Molecular Mechanism, Approaches, and Regulatory Framework

      https://doi.org/10.2174/0113816128364722250126172914

      Novel vaccine formulations called nano vaccines which use nanoparticles (NPs) as adjuvants or carriers, are being developed in place of conventional vaccines. The field of study on peptide-based nano vaccines is enlarging fast as a result of combining antigenic peptides with nano-transport systems. This paper explores advancements in anticancer nano vaccines, focusing on their mechanisms, challenges, and opportunities. It discusses peptide nano vaccines, personalized vaccines, cancer prevention strategies, clinical translation, and self-assembling multivalent nanovaccines. It also discusses nanocarriers' role in delivering tumor-associated antigens and immune-stimulatory adjuvants. In 2024, the American Cancer Society projects over 2 million new cancer cases in the United States, marking the first year this milestone has been surpassed. This equates to approximately 5,480 new cancer diagnoses daily. Additionally, over 611,000 cancer-related deaths are expected, which translates to more than 1,600 deaths per day. The National Centre for Health Statistics mentions the mortality data also shows the various types of cancer percentages. This guideline provides comprehensive recommendations for sponsors submitting a novel drug under Investigation use of curative cancer vaccinations, focusing on safety, effectiveness, dosage optimization, adjuvant use, patient group selection, immune response monitoring, biomarker evaluation, multi-antigen vaccine development, phase-specific difficulties, non-clinical testing, and legal frameworks, while also referencing relevant legal foundations and recommendations.

    • Untargeted Metabolomics and Bioactivities Assessment of , an Endophytic Fungus Isolated from the Leaf of the Plant Linn.

      https://doi.org/10.2174/0113816128337697250106001808
      Introduction

      Fungal endophytes have mutualistic associations with the plant's host, communicating through genetic and metabolic processes. As a result, they gain the ability to generate therapeutically effective metabolites and their derivatives.

      Methods

      The current study aims to assess antioxidant potential along with the identification of robust metabolites within the crude extract of a potent endophytic fungus isolated from leaf tissues of the Linn. plant. Four endophytic fungi were obtained from leaf tissues of Linn., and identified morphologically and molecularly as distinct species. Each ethyl acetate extract of the isolated fungi exhibited a unique chemical profile in the HPTLC fingerprint at various wavelengths. The ethyl acetate (EA) extract from the fungal strain ACL-4 () demonstrated the strongest antioxidant activity among the four fungal endophytes examined, with an EC value of 292.64 ± 3.558 µg/mL. Remarkably, fungal endophyte ACL-4 extract exhibited superior antimicrobial activity at the less concentrations compared to ACL-ME extract of leaf crude.

      Results

      The extract of ACL-ME-treated HEK 293T cells exhibited significant toxicity, with an IC value of 1481.74 ± 23.772 µg/mL, compared to fungal strain ACL-4-treated HEK 293T cells, which had an IC value greater than 2000 µg/mL. Consequently, the crude extract of ACL-4 and ACL-ME along with the standard drug methotrexate exhibited cytotoxic activity against cancer cell line MDA-MB-231 with IC concentrations of 146.65 ± 0.394 µg/mL, 528.46 ± 10.912 µg/mL, and 134.11 ± 3.446 µg/mL, respectively. A total of 2,255 compounds were detected through LC-HRMS-based metabolomics in the crude metabolites of , with certain compounds identified in multiple instances. Among this repertoire, 62 robust bioactive compounds were identified through meticulous screening, guided by existing literature. Comparative HPTLC fingerprint analysis, along with antioxidant efficacy assays of ethyl acetate extracts of derived from leaves and twigs revealed the host-specific production of bioactive chemicals.

      Conclusion

      The top-scoring Keap1 inhibitors derived from , including Pregabalin (-6.083 Kcal/mol), Ferulic acid (-5.434 Kcal/mol), (R)-Piperidine-2-carboxylic acid (-5.31 Kcal/mol), Genipin (-5.197 Kcal/mol), and Brivaracetam (-5.17 Kcal/mol), respectively were considered as Keap 1 inhibitors, potentially mitigate oxidative stress.

    • Crippled Hepatocarcinogenesis Inhibition of Quercetin in Glycolysis Pathway with Hepatic Farnesoid X Receptor Deficiency

      https://doi.org/10.2174/0113816128342642250111055339
      Aim

      Quercetin, a bioactive flavonoid extracted from traditional Chinese medicine, has anti-hepatocellular carcinoma effects. Farnesoid X receptor (FXR), a nuclear receptor highly expressed in the liver, plays important roles in maintaining hepatic glucose homeostasis, anti-inflammation, liver regeneration, and anti-cancer properties. Whether quercetin regulates the glycolysis/glycolysis pathway through FXR signaling remains unknown.

      Methods

      KEGG Enrichment, GO Enrichment, Protein-Protein Interaction (PPI) Network, Molecular Docking, and RNA-Seq Analysis (Swiss Target Prediction, GeneCard databases, Kaplan-Meier Plotter, ). Cell activity, cell proliferation, and cell cycles were separately analyzed by CCK-8 assay, clone formation assay, and flow cytometry. QRT-PCR determined the mRNA levels of related genes in response to quercetin. HPLC-MS/MSHPLC-MS/MS determined the metabolite profiles. FXR deficiency Hep3B cells were used for discriminating the quercetin’s effects with or without FXR.

      Results

      Quercetin-related genes were significantly correlated with FXR in hepatocarcinogenesis, especially in glycolysis. The top 30 related genes between FXR, quercetin, and glycolysis were enriched and chosen to further study. Furthermore, the strongest binding energy determined by the molecular docking model of between quercetin and FXR was -6.55 kcal/mol. Quercetin inhibited cell proliferation by the accumulation of Hep3B cells in the S-phase. The differential expressed genes (C-MYC, PCNA, CYCLIN-D1, and P21) associated with glycolysis were observed. Furthermore, quercetin also inhibited the expression of HK2, GAPDH, and LDHA. Meanwhile, the levels of glycolysis/gluconeogenesis-related metabolites were regulated by quercetin.

      Conclusion

      Quercetin makes an essential anti-HCC effect by crippling the glycolysis/gluconeogenesis process FXR signaling.

    • Efficacy of Roxadustat in Anemia with Chronic Kidney Disease

      https://doi.org/10.2174/0113816128354065250114154721
      Introduction

      Anemia is one of the complications of chronic kidney disease (CKD), and its incidence gradually increases as the disease progresses. A major cause of such anemia is the severe erythropoietin deficiency in CKD. Therefore, improvement in red blood cell production is a choice of treatment. Erythropoiesis-stimulating agents (ESAs) have been used for the therapy of anemia induced in CKD. Roxadustat is a novel drug for improving such anemia. This study aimed to compare the efficacy of roxadustat and ESAs in patients with CKD.

      Materials and Methods

      A retrospective analysis of CKD patients with anemia who regularly use roxadustat and ESAs in the Nephrology Department of the Second Affiliated Hospital of Shantou University School of Medicine was carried out. Baseline clinical data and clinical indicators during the medication period were collected and analyzed in both groups.

      Results

      In this retrospective study, we found that roxadustat was effective in improving anemia. The anemia rate, Hb<11g/dL, before treatment in patients with CKD was 94.55%. The standard rate of patients with CKD anemia was 25.45% after one month of treatment, 54.54% after three months of treatment, and 65.45% after six months of treatment. In the clinical observations of the medication, roxadustat did not differ from ESAs in the treatment of anemia in CKD. However, roxadustat did not improve micro-inflammatory status or increase serum potassium.

      Conclusion

      Roxadustat did not differ from ESAs in the treatment of anemia in CKD patients. However, it has the potential to lower blood lipids and improve iron deficiency.

      Clinical Trial Registration Number

      ChiCTR2300071087.

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