Current Pharmaceutical Biotechnology[JOURNAL]
Sun
200 papers
Ethanolic Extract of Cyperus rotundus Augments Chemosensitivity to Docetaxel and Suppresses Autophagic Flux in HER2-Positive Breast Cancer Cells.
Bian X, Li C, Liu X … +7 more , Liu Z, Song X, Wang F, Wang X, Shao W, Sun H, Yu Z
Curr Pharm Biotechnol · 2025 Jul · PMID 40696560 · Publisher ↗
INTRODUCTION: Breast cancer (BC) represents a malignancy affecting populations globally. Its incidence is on the rise. The ethanolic extract of Cyperus rotundus (EECR) has demonstrated potent anticancer activities agains...
INTRODUCTION: Breast cancer (BC) represents a malignancy affecting populations globally. Its incidence is on the rise. The ethanolic extract of Cyperus rotundus (EECR) has demonstrated potent anticancer activities against multiple human cancer types, inducing apoptosis in BC cells. Autophagic flux protects HER2+ cancer cells from trastuzumab-induced cytotoxicity, so inhibiting it undermines the resistance phenotype. This study aimed to elucidate the therapeutic potential of EECR in trastuzumab-resistant HER2-positive BC and decipher its underlying mechanisms. METHODS: Colony formation assay and Cell Counting Kit-8 (CCK-8) assessed cell viability. Flow cytometry was used for cell cycle analysis and apoptosis detection. Western blotting quantified relevant protein expressions. Nude mice were euthanized prior to tissue harvest. Tumor tissues were excised and processed for histological examination, with 5 μm paraffin sections prepared on glass slides for hematoxylin and eosin (H&E) staining. An orthotopic JIMT-1 cell transplantation tumor model was established, and immunohistochemistry was conducted. RESULTS: EECR demonstrated a dose-dependent suppressive effect on HER2-positive BC cells, inducing apoptosis and G2-M phase cell cycle arrest. It inhibited autophagic flux, as evidenced by LC3 and p62/SQSTM1 accumulation, and upregulated raptor and phosphorylated Mitogen- Activated Protein Kinase (MAPK) in trastuzumab-resistant JIMT-1 cells. Phosphorylated ERK (pERK)/total ERK and Raptor levels were significantly elevated in EECR-treated JIMT-1 cells compared to other treatment groups. Furthermore, EECR significantly inhibited tumorigenic growth in JIMT-1 cells. CONCLUSION: This study reveals that EECR effectively impedes autophagic flux in trastuzumabresistant HER2-positive breast cancer cells, a mechanism increasingly recognized as central to therapeutic resistance. By promoting LC3B and p62 accumulation and modulating the MAPK/mTOR signaling axis, EECR not only disrupts a key survival pathway in resistant cells but also enhances the efficacy of standard chemotherapeutic agents like docetaxel. These dual effects-autophagy inhibition and chemosensitization-underscore EECR's therapeutic potential as an adjuvant strategy to overcome trastuzumab resistance. Given its multi-target nature and favorable safety profile, EECR represents a promising candidate for future combination therapy in refractory HER2-positive breast cancer.
Exploring Immunogenetic Mechanisms in Parkinson's Disease Using Single-Cell Transcriptomics and Mendelian Randomization.
Xu D, Lei Y, Wu J … +3 more , Chen K, Chai S, Xiong N
Curr Pharm Biotechnol · 2025 Jul · PMID 40696559 · Publisher ↗
INTRODUCTION: Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neuron. Although the role of immunity in PD has been increasingly recognized, the imm...
INTRODUCTION: Parkinson's disease (PD) is a prevalent neurodegenerative disorder characterized by the progressive loss of dopaminergic neuron. Although the role of immunity in PD has been increasingly recognized, the immunogenetic mechanisms underpinning its progression remain largely unresolved. METHODS: We employed an integrative approach combining Mendelian randomization (MR), expression quantitative trait loci analysis, and single-cell RNA sequencing to investigate immune cell infiltration and transcriptional regulation in PD. Immune cell composition, pathway activation, and gene regulatory networks were assessed through single-cell gene set enrichment analysis and transcriptional correlation analyses. RESULTS: Immune profiling revealed significant increases in naive B cells (1.22-fold), plasma cells (3.00-fold), switched memory B cells (2.85-fold), and unswitched memory B cells (6.70- fold) in PD patients compared to controls (p < 0.001). MR analysis identified five causal genes- CYTH4, FGR, LRRK2, RIN3, and SAT1- associated with monocyte, neutrophil, and B cell infiltration. SAT1 (OR: 1.529; 95% CI: 1.018-2.297) and RIN3 (OR: 1.222; 95% CI: 1.039- 1.437) showed strong associations with PD risk (p < 0.01). SAT1 positively correlated with PARK7 and regulated reactive oxygen species signaling, while FGR negatively correlated with ABCA4, influencing lipid metabolism and immune responses. DISCUSSION: These findings highlight distinct immunogenetic mechanisms driving PD progression. The SAT1-PARK7 axis appears to modulate oxidative stress and neuroinflammation, whereas the FGR-ABCA4 interaction may affect metabolic and immune pathways. While the study is limited by population heterogeneity and the challenges of inferring causality, it provides mechanistic insights into immune contributions to PD. CONCLUSION: Our integrative genomic analysis identified novel regulatory networks involving immune-related genes in PD, offering potential targets for mechanistic understanding and therapeutic development.
Potential of the β-Myrcene Rich Essential Oil from Astronium Urundeuva (M.Allemão) Engl. (Anacardiaceae) to Potentiate Fluconazole Activity and Inhibit Morphological Transition in Candida Species.
da Costa Silva JT, Almeida Meenezes S, Garcia Novais MH … +16 more , Farias NS, Rodrigues Costa A, Sydney Henrique Felix F, Maia Filho A, Felipe Felicio M, Oliveira da Silvaa N, Pereira GG, Dos Santos Leandro C, Honorio de Oliveira A, Leisla Leandro Nascimento L, Filipi Teles Feitosa L, Gonçalves Ferreira Macedo J, Bezerra Morais-Braga MF, Douglas Melo Coutinho H, Cruz-Martins N, Almeida-Bezerra JW
Curr Pharm Biotechnol · 2025 Jul · PMID 40660452 · Publisher ↗
BACKGROUND: In view of the increasing resistance of Candida species, it is necessary to explore alternative strategies. In this context, essential oils have emerged as promising options, among which the essential oil of...
BACKGROUND: In view of the increasing resistance of Candida species, it is necessary to explore alternative strategies. In this context, essential oils have emerged as promising options, among which the essential oil of Astronium urundeuva (M. Allemão) Engl. has shown potential, as it is traditionally used in folk medicine for the treatment of inflammation and multiple infections. Thus, the aim of this study was to evaluate the chemical profile, anti- Candida activity, and Fluconazole (FCZ) potentiating effect of the essential oil extracted from the leaves of A. urundeuva (EOAU) and its ability to inhibit the virulence mechanism in Candida species. METHODS: The essential oil was obtained via hydrodistillation and characterized using gas chromatography-mass spectrometry. To evaluate the antifungal effects and the modulating activity of Fluconazole (FCZ), the essential oil was diluted in DMSO (1 mL) and SDB medium (9 mL) and tested on 3 Candida strains using the serial microdilution method. In addition, a morphological transition assay was used to evaluate its capacity to inhibit fungal virulence. RESULTS: The major constituent of EOAU was the monoterpene β-myrcene (71.07%). The results indicate that the essential oil exhibits an antifungal effect, with C. tropicalis being the most susceptible species. At subinhibitory concentrations (MC/8), the EOAU enhanced the action of fluconazole against C. krusei and C. tropicalis. The EOAU strongly inhibited the morphological transition in C. tropicalis. CONCLUSION: EOAU is rich in β-myrcene and exhibits an interesting fungistatic effect, making it a great natural candidate for inhibiting Candida spp. virulence.
Advances in Polymer-Based Nanoparticles for Biomedical and Industrial Applications.
Sabei FY
Curr Pharm Biotechnol · 2025 Jul · PMID 40660451 · Publisher ↗
Polymeric nanoparticles (PNPs) are considered to be a revolutionary method for drug delivery and offer significantly more advantages than conventional drug delivery systems. This review synthesizes recent research on bio...
Polymeric nanoparticles (PNPs) are considered to be a revolutionary method for drug delivery and offer significantly more advantages than conventional drug delivery systems. This review synthesizes recent research on biodegradable polymers in drug delivery, emphasizing their properties, modifications, toxicity, and applications in drug absorption. It consolidates key insights from 193 research papers to offer a comprehensive overview of the field, addressing existing research gaps and highlighting various applications. Polymers can be classified based on their structure, source, and biodegradability, which are crucial for assessing their environmental impact and suitability for various applications. Polymers are categorized into two main groups based on biodegradability: biodegradable and non-biodegradable. The primary aim of this review is to elucidate the diverse applications of natural and synthetic biodegradable polymeric nanoparticles, which include cancer treatment, diabetes management, pulmonary drug delivery, and the treatment of ocular infections, all of which are thoroughly explored in this review. Additionally, the role of polymer-based hydrogels is explored as a promising solution in drug delivery. These hydrogels address issues such as poor stability and enhance treatment efficacy by ensuring the sustained release of drugs.
Growth of Chloroquine Crystals and Their Properties as a Beta-Hematin Inhibitor.
Al-Refaia RAK, Al-Khafaji YF, Ali KO … +2 more , Alkarimi AA, Alswafy OB
Curr Pharm Biotechnol · 2025 Jul · PMID 40653834 · Publisher ↗
<p> Introduction: The crystallization of heme into β-hematin and its subsequent conversion to hemozoin has garnered significant interest as a promising target for the development of novel antimalarial therapies, particul...
<p> Introduction: The crystallization of heme into β-hematin and its subsequent conversion to hemozoin has garnered significant interest as a promising target for the development of novel antimalarial therapies, particularly through the heme detoxification pathway. Furthermore, the therapeutic efficacy of chloroquine (CQ) has been widely recognized, with several studies highlighting its role as an inhibitor of β-hematin and hemozoin formation. </p> <p> Methodology: This study reports the synthesis of two novel CQ-derived compounds, 7- chloroquinolin-4-amine (CQC1) and 7-chloro-4-(-oxidaneyl)-3,4-dihydroquinoline (CQC2), and evaluates their individual inhibitory effects on β-hematin formation. </p> <p> Results: Notably, comparative analysis of the experimental data revealed significant variability in the IC50 values for these compounds, which correspond to the concentration required to inhibit 50% of β-hematin synthesis. The impact of incubation time and compound concentration on IC50 values was also investigated. </p> <p> Conclusion: The findings suggest that increasing the concentration and incubation time of both CQ derivatives led to a reduction in their IC50 values, with both compounds demonstrating enhanced inhibitory activity relative to commercial chloroquine (CQ). </p>.
Unveiling the Influence of Culture Conditions on Mesenchymal Stem Cells: A Transcriptome Sequencing Study.
Wang B, Xie J, Pang B … +3 more , Dong F, Zhou J, Zhu H
Curr Pharm Biotechnol · 2025 Jul · PMID 40653833 · Publisher ↗
<p>Aims: To optimize the culture process of Mesenchymal Stem Cells (MSCs) and enhance their biological functions. </p><p> Background: MSCs have shown great potential in treating various diseases due to their low immunoge...
<p>Aims: To optimize the culture process of Mesenchymal Stem Cells (MSCs) and enhance their biological functions. </p><p> Background: MSCs have shown great potential in treating various diseases due to their low immunogenicity and potent paracrine effects. However, the inherent heterogeneity of MSC populations, which can vary depending on the culture conditions, may challenge large-scale clinical application.</p><p> Objective: This study investigates the inconsistency of MSCs cultured in different media, from the transcriptional level to biological functions.</p><p> Method: RNA sequencing was used to identify different expressed genes of MSCs separated and expanded in three media, which were then validated with qPCR. In vitro assays, including proliferation, tube formation, wound healing, multilineage differentiation, paracrine secretome and injured hepatocyte protection assay, were performed to verify the potential differences among three groups.</p><p> Result: MSCs cultured in platelet lysate-containing medium exhibited high expression of genes involved in extracellular matrix regulation, collagen metabolic processes, and angiogenesis, whereas those cultured in serum-free medium demonstrated high expression of genes associated with DNA replication and chromosome segregation. MSCs cultured under serum-containing medium indicated high levels of genes associated with extracellular matrix regulation, cartilage development, and chemotaxis. The results of functional comparative experiments were consistent with the differences in their gene expression patterns. Notably, MSCs cultured in the serum- containing system exhibited greater protective effect against hepatocyte activity.</p><p> Conclusion: Different culture conditions affect the biological functions of MSCs. Optimal conditions should be investigated for applications. Next, an in vivo model should be established to evaluate differences in MSC tissue repair function under various culture conditions.</p>.
Wound Dressing Potential of Bacterial Cellulose Produced by NBRC 16470 Strain Isolated from Rotten Fruits.
Bal H
Curr Pharm Biotechnol · 2026 · PMID 40635226 · Publisher ↗
BACKGROUND: Bacterial cellulose, which is used in many fields from biomedicine to electronics, is promising as an alternative wound dressing instead of traditional gauze in wound treatment. OBJECTIVES: The objective of t...
BACKGROUND: Bacterial cellulose, which is used in many fields from biomedicine to electronics, is promising as an alternative wound dressing instead of traditional gauze in wound treatment. OBJECTIVES: The objective of this study was to evaluate the potential use of cellulose produced by acetic acid bacteria isolated from rotten fruits as a wound dressing. METHODS: In our study, rotten fruit samples were incubated in Hestrin-Schramm (HS) Broth medium. Then, a loopful of the pellicle-forming samples was taken and inoculated onto Hestrin- Schramm (HS) agar using the streak culture method and bacteria were isolated. Identification of bacteria was performed using the BLAST program after 16S rRNA sequence analysis. Physicochemical properties and morphological characterization of bacterial cellulose produced by static culture were examined using Fourier transform infrared (FTIR) and scanning electron microscopy (SEM), respectively, and the swelling ratio was investigated. Antibiotic susceptibilities of bacterial cellulose membranes impregnated with different concentrations of gentamicin (50 μg/mL, 100 μg/mL, 200 μg/mL) against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were determined by the disk diffusion method. RESULTS: The bacteria isolated from rotten fruits were identified as Acetobacter tropicalis NBRC 16470. The structure of cellulose produced by static culture was confirmed by a peak at 3,240 cm in FTIR analysis and fibril structures in SEM analysis. Bacterial cellulose had a swelling ratio of 27.37± 2 .99 fold. The zone diameters formed by bacterial cellulose disk (50 μg/mL gentamicin) and gentamicin (10 μg) disk against Staphylococcus aureus ATCC 29213 and Escherichia coli ATCC 25922 were almost the same. CONCLUSION: The production of bacterial cellulose, which has the potential to be used as a wound dressing from rotten fruits, is important in terms of recycling and low cost.
Flavonoids as Antimicrobial Agents: A Comprehensive Review of Mechanisms and Therapeutic Potential.
Sharma V, Sharma D, Saini M … +11 more , Jain A, Chaudhary J, Kaur N, Sahoo S, Singh SK, Goyal K, Rekha A, Ali H, Gupta S, Hussain MS, Gupta G
Curr Pharm Biotechnol · 2025 Jul · PMID 40619652 · Publisher ↗
Flavonoids, plant-derived polyphenolic compounds, have garnered significant attention for their broad-spectrum antimicrobial potential, encompassing antibacterial, antifungal, and antiviral activities. These bioactive mo...
Flavonoids, plant-derived polyphenolic compounds, have garnered significant attention for their broad-spectrum antimicrobial potential, encompassing antibacterial, antifungal, and antiviral activities. These bioactive molecules exert their effects through multiple mechanisms, including disruption of microbial cell membranes, inhibition of nucleic acid synthesis, suppression of biofilm formation, and interference with key bacterial enzymes. Notable flavonoids such as quercetin, apigenin, and kaempferol exhibit potent activity against bacterial pathogens like Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa, as well as fungal pathogens such as Aspergillus fumigatus and Candida albicans. Furthermore, flavonoids can potentiate the efficacy of conventional antibiotics by inhibiting bacterial efflux pumps, a critical mechanism contributing to antibiotic resistance. Recent advancements in structure-activity relationship (SAR) studies have underscored the influence of structural modifications- such as prenylation, hydroxylation, and methoxylation-on the antimicrobial potency of flavonoids. By highlighting these insights, this review provides a unique perspective on flavonoid-based antimicrobial strategies, particularly their synergistic potential with existing antibiotics. These findings position flavonoids as promising candidates for novel antimicrobial therapies, particularly in the face of increasing antibiotic-resistant pathogens. However, further research is needed to elucidate their precise mechanisms and optimize their therapeutic applications.
Green Synthesis of Silver Nanoparticles Using Vahl Leaf Extract: Characterisation, Process Optimisation, and Hepatoprotective Activity Against Paracetamol-induced Liver Toxicity in Rats.
Devi DR, Kahsay MH, Battu GR … +2 more , Basavaiah K, Tatipamula VB
Curr Pharm Biotechnol · 2025 · PMID 40611407 · Publisher ↗
INTRODUCTION: Scientists around the world are focusing on 'green,' environmentfriendly, and cost-effective green synthesis of nanometals using various plant extracts to combat various ailments. Among nanometals, Silver (...
INTRODUCTION: Scientists around the world are focusing on 'green,' environmentfriendly, and cost-effective green synthesis of nanometals using various plant extracts to combat various ailments. Among nanometals, Silver (Ag) is one of the most commercialised nanomaterials due to its wide applications in biotechnology and biomedical fields. The present study reports the first facile synthesis, characterization, and process optimisation of Ag nanoparticles (NPs) using aqueous Grewia tiliaefolia leaf extract (Gt) as a reducing and surface functionalising agent. METHODS: Characterisation of Gt-mediated Ag-NPs was performed using FTIR. The morphology and microstructures of Gt-derived Ag-NPs were analysed using TEM and FE-SEM. In vitro, antioxidant activity was evaluated against DPPH radicals, hydrogen peroxide radicals, and ferric ions. In vitro, anticancer activity was assessed on MCF-7 and HepG2 cell lines. , hepatoprotective activity was tested against paracetamol-induced liver toxicity in rats. RESULTS: FTIR analysis confirmed the interaction between Ag-NPs and Gt. The optimal conditions for Gt-derived Ag-NPs were found to be 4 mM AgNO, 5% Gt, at 90°C for 60 minutes, at pH 9. UV-Visible spectroscopy, XRD, FE-SEM, and TEM revealed the phase formation, spherical morphology, and surface functionalisation of Gt-derived Ag-NPs, which were stable (-28.3 mV) with an average particle size of 14.5±0.05 nm. The Gt-derived Ag-NPs were found to be highly effective in significantly inhibiting DPPH radical, ferric ions, and hydroxyl radicals. Additionally, the cytotoxicity of Gt-derived Ag-NPs was more effective against MCF-7 cells compared to HepG2 cells. They also exhibited dose-dependent protection against hepatoprotective activity in albino rats. DISCUSSION: The hepatoprotective effects of Gt-mediated Ag-NPs likely result from the combined action of bioactive phytochemicals (such as α/β-amyrin, γ-lactones, betulin, and lupeol), and their ability to scavenge ROS, reduce oxidative stress, and modulate inflammatory pathways. These mechanisms, supported by reduced lipid peroxidation and increased antioxidant activity in paracetamol-induced hepatotoxicity, suggest their therapeutic potential in liver protection and regeneration. CONCLUSION: Overall, Gt proves to be an eco-friendly and non-toxic source for synthesizing bioactive Ag-NPs at optimal conditions.
Elucidating the Role of Gardeniae Fructus and Scutellariae Radix Herb Pair in Alzheimer's Disease via Network Pharmacology: Emphasis on Oxidative Stress, and the PI3K/Akt Pathway.
Ye JX, Wu JY, Zhu M … +2 more , Ai L, Huang Q
Curr Pharm Biotechnol · 2025 Jun · PMID 40600562 · Publisher ↗
BACKGROUND: The combination of Gardeniae Fructus (ZZ) and Scutellariae Radix (HQ) is a traditional Chinese medicine used for Alzheimer's disease (AD). However, the molecular mechanisms underlying its anti-dementia effect...
BACKGROUND: The combination of Gardeniae Fructus (ZZ) and Scutellariae Radix (HQ) is a traditional Chinese medicine used for Alzheimer's disease (AD). However, the molecular mechanisms underlying its anti-dementia effects, particularly its multi-component synergy and pathway modulation, remain poorly understood. OBJECTIVE: Our study employed an integrated systems pharmacology approach to mechanistically decode the anti-AD properties of ZZ-HQ, combining network pharmacology predictions, molecular docking simulations, and experimental validation to identify critical bioactive components, molecular targets, and therapeutic pathways. METHODS: A comprehensive network pharmacology analysis was performed to identify bioactive compounds within the ZZ-HQ complex and their potential protein targets associated with AD. Molecular docking was utilized to predict and assess the binding interactions between key bioactive compounds and AD-related protein targets. Experimental validation focused on baicalin, a major active compound in the ZZ-HQ complex, evaluating its effects on cell viability, apoptosis regulation, oxidative stress reduction, and the activation of the PI3K/Akt signaling pathway. RESULTS: Fifty-four bioactive compounds were identified in the ZZ-HQ complex, interacting with 258 AD-associated proteins. Key compounds, such as baicalein and norwogonin, demonstrated strong binding affinities with pivotal proteins, including SRC and PIK3R1. Experimental studies further confirmed that baicalin significantly improved cell viability by activating the PI3K/Akt pathway, reducing apoptosis, and alleviating oxidative stress. CONCLUSION: Our study uncovered the therapeutic potential of the ZZ-HQ combination in addressing AD through multi-target mechanisms, particularly via modulation of the PI3K/Akt pathway and oxidative stress. These findings provide a scientific basis for the pharmacological effects of ZZ-HQ and offer valuable insights for further research on its potential application in AD treatment.
HIV Co-infected with Asymptomatic Visceral Leishmaniasis Exhibited a High Prevalence of the B type HBV Genotype.
Kumar S, Sahoo GC, Pandey K … +1 more , Kumar A
Curr Pharm Biotechnol · 2025 · PMID 40600561 · Publisher ↗
BACKGROUND: Multiple organisms infect the host simultaneously in the case of coinfection. This study intended to determine the prevalence of viral hepatitis B in HIV/Asymptomatic VL co-infected patients and to identify t...
BACKGROUND: Multiple organisms infect the host simultaneously in the case of coinfection. This study intended to determine the prevalence of viral hepatitis B in HIV/Asymptomatic VL co-infected patients and to identify the HBV genotype circulating in these patients in Bihar, India. METHODS: There were 96 archived samples with co-infection with HIV and asymptomatic VLpositivity included in this study. A real-time PCR test was performed to measure the load of HBV DNA, and a chemiluminescent immunoassay was performed to determine the level of HBsAg. RESULTS: Our study evaluated HIV and AVL co-infected patients with two coexisting genotypes of HBV and observed the expression of the B, C, and D genotypes. HBsAg levels correlated directly with HBV DNA levels in almost every case. CONCLUSION: For a better understanding of this disease, authors need approaches and strategies for improving the current diagnostic techniques, as well as studies focusing on vector control procedures and other operational tools.
Challenges and Progress of Orphan Drug Development for Rare Diseases.
Debnath A, Mazumder R, Mazumder A … +2 more , Tyagi PK, Singh RK
Curr Pharm Biotechnol · 2025 Jun · PMID 40600560 · Publisher ↗
Rare diseases, defined as conditions affecting fewer than 200,000 people in the United States or less than 1 in 2,000 people in Europe, pose significant challenges for healthcare systems and pharmaceutical research. This...
Rare diseases, defined as conditions affecting fewer than 200,000 people in the United States or less than 1 in 2,000 people in Europe, pose significant challenges for healthcare systems and pharmaceutical research. This comprehensive review examines the evolving landscape of orphan drug development, analyzing scientific, economic, and regulatory challenges while highlighting recent technological breakthroughs and innovative approaches. We explore how artificial intelligence, next-generation sequencing, and personalized medicine are revolutionizing rare disease research and treatment development. The review details key advances in therapeutic approaches, including gene therapy, cell-based treatments, and drug repurposing strategies, which have led to breakthrough treatments for previously untreatable conditions. We analyze the impact of international collaborations, such as the International Rare Diseases Research Consortium, and discuss how regulatory frameworks worldwide have evolved to accelerate orphan drug development. The paper highlights the growing market for orphan drugs, projected to reach $242 billion by 2024 while examining the complex challenges of ensuring treatment accessibility and economic sustainability. We assess innovative clinical trial designs, patient registry development, and emerging strategies in personalized medicine that are transforming the field. Despite notable advancements, significant gaps remain in diagnosis, treatment accessibility, and sustainable funding for rare disease research. The review concludes by proposing specific actions for enhancing international collaboration, improving patient registries, and aligning incentives to address the unmet medical needs of rare disease patients, emphasizing the critical role of continued public-private partnerships and technological innovation in advancing orphan drug development.
A Multidisciplinary Approach for Developing a Natural Antifungal Formulation Targeting Oropharyngeal Candidiasis: A Mini-review.
Rajkhan AT, Medhesh OI, Bafail D … +4 more , Ahmed OA, Musa AA, Ali AS, Ibrahim IM
Curr Pharm Biotechnol · 2025 Jun · PMID 40600559 · Publisher ↗
BACKGROUND: Oropharyngeal candidiasis (OPC), a fungal infection affecting the mouth and throat, imposes a substantial burden on vulnerable populations such as HIV/AIDS patients, cancer treatment recipients, and the elder...
BACKGROUND: Oropharyngeal candidiasis (OPC), a fungal infection affecting the mouth and throat, imposes a substantial burden on vulnerable populations such as HIV/AIDS patients, cancer treatment recipients, and the elderly. Conventional antifungal medications are encountering increasing resistance and side effects, necessitating the exploration of novel therapeutic approaches. OBJECTIVES: This review proposes a comprehensive strategy for developing a novel natural product- based antifungal formulation targeting OPC. The approach involves harnessing promising natural compounds with established antifungal properties and employing advanced delivery systems like mucoadhesive microemulsions to improve efficacy and minimize adverse effects. Additionally, the review explores the integration of computational methods to expedite the identification and development of potent antifungal agents. METHODS: A comprehensive literature review was conducted using databases such as PubMed, Scopus, and Web of Science. Search terms included combinations of "oropharyngeal candidiasis," "natural antifungal agents," "flavonoids," "mucoadhesive microemulsions," "computational drug discovery," and "in vitro/in vivo studies." Priority was given to studies published within the last ten years. RESULTS: The review identifies promising natural compounds with antifungal activity against Candida species commonly associated with OPC. Additionally, several studies highlight the potential of computational tools such as molecular docking and in silico ADMET for rapidly identifying natural compounds with potent antifungal activity and favorable pharmacokinetic and safety profiles. A brief overview of in vitro and in vivo experiments is provided, emphasizing their role in validating the safety and efficacy of the proposed natural product-based antifungal formulation. Formulation and analytical aspects are also discussed. CONCLUSION: The multidisciplinary approach outlined, incorporating natural products, computational methods, advanced preclinical in vitro and in vivo experiments, and advanced delivery systems, offers promise for the rapid, cost-effective development of safe and effective optimized formulations to address the growing challenge of OPC, particularly in vulnerable populations.
Towards a Personalized Medicine Approach for HCC.
Tippani R, Kagithoju P, Pabbati R … +2 more , Mallu MR, Porika M
Curr Pharm Biotechnol · 2025 Jun · PMID 40600558 · Publisher ↗
Owing to the lack of appropriate selective treatments, hepatocellular carcinoma (HCC) remains one of the major reasons of cancer associated death. Chronic liver failure nearly always accompanies HCC, and doctors usually...
Owing to the lack of appropriate selective treatments, hepatocellular carcinoma (HCC) remains one of the major reasons of cancer associated death. Chronic liver failure nearly always accompanies HCC, and doctors usually detect it only after the disease has progressed beyond the point where curative therapies are possible. Despite the fact that HCC has distinct morphological and phenotypic patterns, therapeutic options are limited to comparatively homogeneous drugs such as multi-targeted tyrosine kinase blockers and immune checkpoint blockers. Multiple studies evaluating the effectiveness of different medications have yielded disappointing findings, indicating that HCC has poor immunity to chemotherapy, which is exacerbated by multidrug resistance. As a result, more successful therapies addressing HCC's disordered metabolic and molecular pathways are needed. The quite often change in sequence of genes and molecular targets in HCC patients are telomerase reverse transcriptase, Wnt/-catenin signaling pathway oncogene (CTNNB1), and the TP53 gene, according to integrated genomic profiling. Furthermore, new approaches like genome-scale metabolic replicas may be utilized to explicate the basic cancer specific metabolism, allowing for such exploration of promising biomarkers and drug candidates. The clinical implications of metabolic network driven heterogeneity of HCCcaseson the basis of redox response, metabolite use, and subtype specific pathways could help accelerate the advancement of personalised medicine. Another interesting strategy is microRNA- based therapy which involves miRNA antagonists to block oncogenic miRNAs and miRNA substitution, which entails reintroducing a tumor-suppressor miRNA to restore function following a functional impairment. The existing and evolving clinical purpose in context of molecular targets and metabolic network-based approaches are summarised in this review, paving the way for successful HCC patient care.
Design and Preliminary Investigation on Core Shell Nanoparticles Laden Gel for Corneal Neovascularization.
Desai H, Shah P, Sawant V … +1 more , Singh R
Curr Pharm Biotechnol · 2026 · PMID 40417753 · Publisher ↗
BACKGROUND: The inherent limitation of ocular dosage forms is decreased precorneal residence time which affects the bioavailability and therapeutic efficacy. OBJECTIVE: The objective of the current research was to sustai...
BACKGROUND: The inherent limitation of ocular dosage forms is decreased precorneal residence time which affects the bioavailability and therapeutic efficacy. OBJECTIVE: The objective of the current research was to sustain drug release and enhance precorneal drug residence time by formulating lipidic core-shell nanoparticles of Dexamethasone Sodium Phosphate and loading them in ion-sensitive in situ gel for corneal neovascularization. METHODS: Polymeric nanoparticles were formulated using Eudragit L100-55 and PVA by twostep solvent diffusión nanoprecipitation method and coated by a lipidic film of Soya phosphatidylcholine with Cholesterol. The optimized lipidic core-shell nanoparticles were transformed into gel using Gellan gum. The lipidic core-shell nanoparticles were evaluated for particle size, zeta potential, entrapment efficiency, reléase and in situ gel was evaluated for gelling time, pH, drug content, HETCAM studies, etc. Results: The Core-shell lipid nanoparticles exhibited a particle size of 368.00±0.54 nm and zeta potential -13.3±2.0 mV respectively. The lipidic core-shell nanoparticles were found to show a sustained drug release when compared to the drug solution. The optimized in situ gel was found to show a gelation time of 39.59±2.49 seconds and was found to be non-irritant. CONCLUSION: A decline in ex vivo drug permeation was observed through an aqueous suspension of core-shell polymeric nanoparticles and core-shell LPN loaded in situ gel thus confirming sustained release for the drug Dexamethasone Sodium Phosphate.
A Novel Weight Loss Mechanism of Hydroxysafflor Yellow A in Obese Mice: Involvement of Immune Inflammation via Prkcd, Btk, and Vav1 Genes in Adipose Tissue.
Hou R, Hu W, Yan K … +9 more , Lyu X, Jiang Y, Guo X, Zhao Y, Wang L, Yang H, Zhu H, Pan H, Gong F
Curr Pharm Biotechnol · 2026 · PMID 40415317 · Publisher ↗
INTRODUCTION: Hydroxysafflor Yellow A (HSYA), known for its anti-inflammatory effects in cardiovascular diseases, has also been shown to reduce adiposity and improve metabolic disorders in diet-induced obese (DIO) mice....
INTRODUCTION: Hydroxysafflor Yellow A (HSYA), known for its anti-inflammatory effects in cardiovascular diseases, has also been shown to reduce adiposity and improve metabolic disorders in diet-induced obese (DIO) mice. However, the molecular mechanisms underlying its anti-obesity effects, particularly whether they are mediated through immune-inflammatory pathways, remain unclear. This study aims to identify the key molecular mechanisms involved in HSYA's anti-obesity action. METHODS: Male C57BL/6J mice were divided into three groups: Standard Feed (SF), High-Fat Diet (HFD), and HFD with HSYA treatment (250 mg/kg/day for 9 weeks). Whole transcriptome sequencing of White Adipose Tissue (WAT) identified Differentially Expressed Genes (DEGs), which were integrated with network pharmacology predictions to identify key molecular targets of HSYA. RT-qPCR in WAT, 3T3-L1 adipocytes, and RAW264.7 macrophages validated the core genes, and molecular docking assessed HSYA's binding affinity with these targets. RESULTS: HSYA treatment significantly reduced body weight (35.27 ± 1.27g vs. 45.46 ± 1.68g, p < 0.05) and WAT mass (3.38±0.21g vs. 1.86±0.27g, p < 0.05) in DIO mice and ameliorated glucose and lipid metabolism abnormalities. Transcriptome analysis revealed 739 DEGs, with 21 overlapping genes identified between sequencing and network pharmacology analyses. Experimental validation highlighted Prkcd, Btk, and Vav1 as core genes within immune-inflammatory pathways, including chemokine and B cell receptor signaling, which are implicated in obesityrelated inflammation. RT-qPCR confirmed the downregulation of Prkcd, Btk, and Vav1 after HSYA treatment, consistent with transcriptomic findings. Molecular docking analysis demonstrated strong binding affinities between HSYA and VAV1 (-8.5 kcal/mol), BTK (-6.9 kcal/mol), and PRKCD (-6.6 kcal/mol). CONCLUSION: HSYA demonstrates the therapeutic potential for obesity by modulating immuneinflammatory pathways in WAT, specifically targeting Prkcd, Btk, and Vav1 in mice. Given its clinical use in cardiovascular disease, these findings suggest that HSYA may offer broader therapeutic benefits, including obesity management, though further studies are needed to clarify the mechanisms and assess its applicability to humans.
Causal Relationships Between Specific Gut Microbiota Taxa, Plasma Metabolites, and Cerebral Small Vessel Disease Risk: A Mendelian Randomization Analysis.
Zhao X, Li Y, Lu T … +3 more , Yan H, Xue C, Li J
Curr Pharm Biotechnol · 2025 May · PMID 40396296 · Publisher ↗
AIMS: This study investigates causal relationships between gut microbiota (GM), plasma metabolites, and cerebral small vessel disease (CSVD), with a focus on identifying GM taxa and metabolites that mediate disease risk....
AIMS: This study investigates causal relationships between gut microbiota (GM), plasma metabolites, and cerebral small vessel disease (CSVD), with a focus on identifying GM taxa and metabolites that mediate disease risk. METHODS: Summary data from genome-wide association studies on GM (MiBioGen), 1,400 plasma metabolites, and CSVD were analyzed using a two-step Mendelian randomization (MR) approach. The primary analysis utilized inverse-variance weighting, complemented by weighted median, weighted mode, and MR-Egger methods for robustness. RESULTS: The MR analysis identified 12 GM taxa associated with CSVD risk, including 7 taxa linked to increased risk (Veillonellaceae, Hungatella, Ruminococcus2, Lachnospiraceae UCG010, Streptococcus, Cyanobacteria, Verrucomicrobia) and 5 taxa linked to decreased risk (Faecalibacterium, Alphaproteobacteria, Eubacterium nodatum group, Fusicatenibacter, Rhodospirillales). Additionally, 10 plasma metabolites were causally associated with CSVD risk, with sphingomyelin (d18:2/14:0, d18:1/14:1), nicotinamide, and 3-ethylcatechol sulfate (2) linked to increased risk, while phosphate-to-uridine ratio, adenosine 5'-diphosphate (ADP)-toflavin adenine dinucleotide (FAD) ratio, arginine, caffeine-to-theobromine ratio, N-succinylphenylalanine, sphingosine, and phenylpyruvate-to-4-hydroxyphenylpyruvate ratio were linked to decreased risk. Mediation analysis identified 8 causal pathways through which plasma metabolites connect GM taxa to CSVD. CONCLUSION: These findings underscore the substantial influence of GM and plasma metabolites on CSVD risk, highlighting potential therapeutic targets. Further investigation is needed to elucidate the biological mechanisms underlying these associations.
Naringin Alleviates Digoxin-induced Nephrotoxicity via Regulating Nrf2/HO-1 and PI3K/ AKT/TGF-β Cascades in Rats' Renal Tissues.
Said HK, Rabie ASI, Said ASA … +6 more , AlAhmad MM, Hussein RRS, Mady M, El-Kalaawy AM, Hashem KS, Ahmed AE
Curr Pharm Biotechnol · 2025 Apr · PMID 40396295 · Publisher ↗
BACKGROUND: Nephrotoxicity limits the clinical application of digoxin. One area that might be useful is the mechanical knowledge of altered renal function and renal impairment. We hypothesized that co-administration of n...
BACKGROUND: Nephrotoxicity limits the clinical application of digoxin. One area that might be useful is the mechanical knowledge of altered renal function and renal impairment. We hypothesized that co-administration of naringin would affect digoxin nephrotoxicity by alleviating the altered renal oxidative/ antioxidant redox and apoptotic cascade. METHOD: 40 male Wistar Albino rats (200 ± 50 g) were grouped into 4, every group included (n= 7), control, Nar., Dig. and Nar. + dig. Groups. Colorimetric estimation of kidney functions and renal oxidative/ antioxidant redox were done. RESULTS: Comparing digoxin alone, the concomitant administration of digoxin and naringin restored renal antioxidant/ oxidative redox, redistributed Nrf2, HO-1 mRNA exposure with a concomitant down-regulation of NF-κB, AKT and PI3K mRNA expressions. Moreover, a significant decrease of Smad3 and transforming growth factor-β (TGF- β) protein concentrations with a simultaneous rise of Smad7 were noticed in Nar. + dig. Arm when compared to Dig. group. CONCLUSION: The co-administration of naringin and digoxin can mitigate digoxin-mediated nephrotoxicity by introducing antioxidant action. This is done by maintaining effects on renal oxidative/antioxidant cycle and lethality via regulating AKT/ PI3k/ Smad3/ Smad7 signaling pathways.
Analysis of the Mechanism of PGLP-1 Inhibiting Gluconeogenesis Based on Whole Transcriptome Sequencing.
Gao H, Yu H, Tong W … +4 more , Fan W, Mai Y, Feng W, Qiu Y
Curr Pharm Biotechnol · 2025 May · PMID 40390217 · Publisher ↗
OBJECTIVE: Through comprehensive transcriptome sequencing of liver RNA in mice induced with streptozotocin (STZ) to develop hyperglycemia, we uncovered crucial genes associated with hyperglycemic processes, shedding ligh...
OBJECTIVE: Through comprehensive transcriptome sequencing of liver RNA in mice induced with streptozotocin (STZ) to develop hyperglycemia, we uncovered crucial genes associated with hyperglycemic processes, shedding light on their respective functions. Furthermore, we delved deeply into a discussion surrounding the mechanism behind plasma glucagon-like peptide 1 (PGLP-1) and its role in inhibiting gluconeogenesis. METHODS: Liver tissues from mice induced with STZ to develop hyperglycemia (M group), as well as those treated with PGLP-1 (P11 group) and Exendin-4 (E group), were collected. RNA extraction was performed for comprehensive transcriptome sequencing. Differentially expressed mRNA, microRNA (miRNA), and long-chain non-coding RNA (lncRNA) were identified and subjected to analysis of their respective GO and KEGG pathways. An association network involving mRNA-miRNA-lncRNA was constructed to pinpoint target molecules associated with gluconeogenesis. Furthermore, personalized analysis focused on eight gluconeogenesis-related signal pathways obtained from KEGG. RESULTS: A total of 289 differentially expressed mRNA (dif-mRNA), 21 differentially expressed miRNA (dif-miRNA), and 463 differentially expressed lncRNA (dif-lncRNA) were screened from the M group and P11 group. 182 dif-mRNA, 239 dif-miRNA, and 384 dif-lncRNA were screened from the M group and E group. A total of 427 dif-mRNA, 261 dif-miRNA, and 525 diflncRNA were screened from the E group and the P11 group. Among them, mRNA was enriched to the PI3K-Akt signaling pathway, Type ll diabetes mellitus, the Insulin signaling pathway, and the PPAR signaling pathway, while lncRNA was mainly enriched in PI3K-Akt signaling pathway. Similar to the whole transcriptome sequencing, the results of gluconeogenesis personalized analysis showed that the PI3K-Akt signaling pathway was the key pathway, and Gck and Cyp7a1 were highly expressed after PGLP-1 was administered. CONCLUSIONS: According to our findings, we believe that PGLP-1 is a potential regulator of noncoding RNAs, including miRNAs and lncRNAs. Additionally, it modulates the PI3K-Akt signaling pathway, resulting in the upregulation of GcK and Cyp7a1. In this way, it effectively inhibits gluconeogenesis.
Trojan Horses: A Secret Route for Nanomedicines.
Amin Z, Nadeem D, Shakil H … +3 more , Jatoi MA, Baloch R, Ali R
Curr Pharm Biotechnol · 2025 · PMID 40390216 · Publisher ↗
The nanoparticles are widely used in various drug delivery applications due to their versatility to encapsulate, cargo loading, and transport of therapeutic agents. Numerous studies have explored the use of nanomedicine-...
The nanoparticles are widely used in various drug delivery applications due to their versatility to encapsulate, cargo loading, and transport of therapeutic agents. Numerous studies have explored the use of nanomedicine-based drug delivery systems for treating various diseases. This research provides a smart and precise review of one of the nanoparticles-based drug delivery approaches, i.e., the Trojan horse strategy which is employed for delivering the drug to the target efficiently and reliably. Furthermore, the applicability of nanomedicines to cancer treatment is discussed, with examples drawn from various systematic studies. The use of different nanomedicine platforms such as liposomes, nanoparticles, spherical nucleic acids, extracellular vesicles, and immune cells acting as Trojan horses is also explored in the context of cancer therapy. Finally, a precise conclusion and future recommendations are provided for future researchers in the field of applied nanotechnology for the pharmaceutical domain.
About
- Frequency
- Sun
- Papers found
- 200
- RSS feed
- Subscribe