Current Pharmaceutical Biotechnology[JOURNAL]
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200 papers
Unveiling the Role and Mechanism of Mycoprotein for Reducing Cardiovascular Risk.
Kumar A, Bawa Y, Pramanik J … +5 more , Batta K, Prajapati B, Mehra R, Menkinoska M, Petkoska AT
Curr Pharm Biotechnol · 2025 May · PMID 40375709 · Publisher ↗
Cardiovascular diseases (CVDs) have the highest mortality rates worldwide. To reduce the risk of CVDs, dietary interventions are a potential approach. This review explores the potential of mycoprotein, a fungal-derived p...
Cardiovascular diseases (CVDs) have the highest mortality rates worldwide. To reduce the risk of CVDs, dietary interventions are a potential approach. This review explores the potential of mycoprotein, a fungal-derived protein, as a dietary approach for maintaining cardiovascular health. A comprehensive literature search was conducted using various databases (Web of Science, Medline, Scopus, Google Scholar, EBSCO, PubMed) and government websites (WHO, CDC) to identify relevant studies. Mycoprotein provides essential amino acids with high bioavailability (0.996) while containing minimal saturated fat (1.5 grams) and high fiber (6 grams). Clinical studies have shown that mycoprotein consumption reduces cholesterol, improves lipid profiles, and potentially lowers blood pressure, possibly due to its impact on gut microbiota (GM) and short-chain fatty acids (SCFAs) production. The intestinal fermentation of mycoprotein fiber increases the abundance of beneficial gut bacteria, binds to Gprotein coupled receptors like GPR41 and 43 to promote vasodilation, inhibits the angiotensinconverting enzyme, and reduces hepatic cholesterol production. Chitin and beta-glucan, the primary fiber of mycoprotein, exhibit anti-inflammatory properties that may contribute to overall cardiovascular health. The study concludes that mycoprotein is a sustainable and nutritious alternative, and its consumption promotes cardiovascular health and reduces CVD risks.
Optimization of Hesperidin Nanoparticles as a Promising CYP2E1 and CYP3A11 Regulator in Paracetamol-Intoxicated Mice.
Mohamed MM, Hussein MA, Elashmony SM … +3 more , Saifeldeen ER, Roshdy T, Metwaly AM
Curr Pharm Biotechnol · 2025 May · PMID 40370238 · Publisher ↗
BACKGROUND: Hesperidin is a flavonoid found in citrus fruits, particularly in the peel and pulp of oranges and lemons. By encapsulating drugs or bioactive compounds within NPs, it's possible to enhance their stability, s...
BACKGROUND: Hesperidin is a flavonoid found in citrus fruits, particularly in the peel and pulp of oranges and lemons. By encapsulating drugs or bioactive compounds within NPs, it's possible to enhance their stability, solubility, and bioavailability. The current investigation aims to optimize hesperidin nanoparticles (Hes-NPs) and evaluate their hepatoprotective and antioxidant effects in paracetamol-intoxicated mice. METHODS: The characteristics of Hes-NPs were elucidated, including morphology, particle size, zeta potential, UV-vis, entrapment efficiency, and FT-IR spectra. Hes-NPs were also tested for their hepatoprotective and antioxidant effects in paracetamol-treated mice. Safety and toxicity assessments are crucial before pharmacological studies. In addition, liver enzymes, oxidative stress, inflammatory biomarkers, and gene expression of CYP2E1 and CYP3A11 were measured. Furthermore, the study examined the molecular docking of hesperidin with the CYP2E1 and CYP3A11 proteins. RESULTS: The synthesized Hes-NPs were uniform, spherically shaped, and well dispersed, with no aggregation noted, with a size range of 155.12 ± 14.13 nm. The measured zeta potential value of Hes-NPs was -21.57 ± 0.8 mV with a polydispersity index (PDI) of 0.49. Also, the UV spectra of hesperidin are at 220 and 279 nm, and Hes-NPs have strong absorption at 225 and 280 nm. Also, the LD50 of Hes-NPs was 1137.5 mg/kg b.w. Moreover, administering paracetamol-intoxicated mice with Hes-NPs resulted in improved plasma lipid profile (TC, TG, and HDL-C) and liver enzymes (ALT, AST, ALP, and LDH) as well as oxidative stress (GSH, SOD, CAT, Pr-SHs, and MDA) and inflammatory (TNF-α) biomarker levels, as well as attenuated CYP2E1, and CYP3A11 gene expression. In-silicon results proved that hesperidin showed a stronger estimated binding affinity with a ∆G of -8.6 and -10.5 kcal/mol. towards CYP2E1, and CYP3A11 activity, respectively. Our results showed that hesperidin forms hydrogen bonds with amino acid residues through the 9 and 12 bonds of CYP2E1 and CYP3A11, respectively. CONCLUSION: Hes-NPs could offer several advantages. It can be designed to specifically target liver cells, minimizing off-target effects, enhancing bioavailability, and shielding hesperidin from degradation in the body. The current results suggest that Hes-NPs may enhance antioxidant defenses and protect against oxidative stress in paracetamol-intoxicated mice.
Circ-LRP6 Inhibits the Development and Progression of AAA miR-29a-3p/HIF-1α Axis.
Wang F, Sun Z, Yan W … +1 more , Wang H
Curr Pharm Biotechnol · 2025 · PMID 40357770 · Publisher ↗
BACKGROUND: At present, the research on the potential molecular mechanism of abdominal aortic aneurysm (AAA) is limited, which hinders the treatment of aneurysm and the development of drugs. CircRNA has been identified a...
BACKGROUND: At present, the research on the potential molecular mechanism of abdominal aortic aneurysm (AAA) is limited, which hinders the treatment of aneurysm and the development of drugs. CircRNA has been identified as a potential therapeutic target for diagnostic biomarkers in a variety of diseases. The purpose of this study was to explore the molecular mechanism of circLRP6 in AAA and to provide a theoretical basis for further clinical optimization of treatment. METHODS: The animal model and cell model of AAA were constructed, and the circLRP6 expression was verified by in situ hybridization and qRT-PCR. The effect of circLRP6 on cell viability was determined using CCK-8 and BrdU. The effects of circLRP6 on the cell cycle and apoptosis were determined by flow cytometry. In addition, the interaction of circLRP6 with miR-29a-3p and HIF-1α was verified by the luciferase reporter gene and RIP. HIF-1α or caspase 3 expression was detected by immunofluorescence or western blot analysis. RESULTS: Our previous results showed that the circLRP6 had reduced expression in AAA, and its overexpression significantly inhibited AngII-induced hAoSMC cell viability. In addition, bioinformatics prediction showed that there was a binding site between miR-29a-3p and circLRP6, showing a negative regulatory relationship in hAoSMC. In addition, the results of the luciferase reporter gene and RIP showed that the circLRP6 interacted with HIF-1α, and achieved effective treatment of AAA by inhibiting the miR-29a-3p/HIF-1α. CONCLUSION: CircLRP6 effectively inhibited the development of AAA by inhibiting the miR- 29a-3p/HIF-1α, providing a theoretical basis for further clinical optimization of treatment.
Antifungal Resistance in Vaginal Candidiasis Among Reproductive-age Women: A Review.
Mallick U, Sahu BK, Hegde R … +4 more , Jena P, Turuk J, Sahu MC, Panda SK
Curr Pharm Biotechnol · 2025 May · PMID 40353419 · Publisher ↗
Candida is a type of fungus that can cause infections in humans. Sometimes, these infections become tough to treat because the Candida fungus resists antifungal drugs. This resistance depends on both the specific type of...
Candida is a type of fungus that can cause infections in humans. Sometimes, these infections become tough to treat because the Candida fungus resists antifungal drugs. This resistance depends on both the specific type of Candida and how it interacts with the human body. For instance, Candida can change its genetic makeup or produce proteins that pump out the drugs, making them less effective. Additionally, Candida can form a protective layer called a biofilm, which shields it from the drugs. Candida can cause a variety of diseases, and vaginal candidiasis is among the most troublesome. Nearly every woman experiences this infection at least once in her lifetime. Higher rates of treatment failures and recurrent infections result from the developing issue of antifungal resistance, underscoring the need for a more thorough understanding of resistance mechanisms. Changes in hormonal levels and immune responses can significantly influence the effectiveness of antifungal treatments. Hormonal fluctuations can alter vaginal pH and immune functions, which in turn affects Candida colonization and persistence. Moreover, an imbalance in the vaginal microbiome can lead to an overgrowth of Candida and lead to the drug resistance candidiasis. This review delves into the molecular pathways that contribute to the resistance of vaginal candidiasis to antifungal treatments, focusing on both acquired and intrinsic resistance mechanisms. Acquired resistance develops due to genetic alterations following antifungal exposure, including mutations in genes encoding drug targets, overexpression of efflux pumps, and increased biofilm formation. In contrast, intrinsic resistance refers to the innate traits of the Candida species that inherently reduce the efficacy of antifungal agents. These characteristics include changes in membrane sterols, genetic mutations in target enzymes, and the presence of efflux pumps that remove antifungal medications. Understanding these complex mechanisms can inform future therapeutic strategies and improve clinical outcomes.
Optimization and Characterization of Khellin Loaded Nanogel for the Potential Use in Psoriasis Management.
Topuzoğlu S, Yapar EA, Abdo L … +5 more , Esentürk-Güzel İ, Yurtsever AG, Gümrükçü S, Erdal MS, Sindhu RK
Curr Pharm Biotechnol · 2025 May · PMID 40326037 · Publisher ↗
BACKGROUND: Psoriasis is a chronic skin disease that affects patients' quality of life. Treating psoriasis remains a significant challenge due to various factors, including individual response variability, drug resistanc...
BACKGROUND: Psoriasis is a chronic skin disease that affects patients' quality of life. Treating psoriasis remains a significant challenge due to various factors, including individual response variability, drug resistance, and the range of side effects associated with currently available medications. Nowadays, numerous research efforts are being made aiming at overcoming the obstacles of the available psoriasis treatments are still taking place. OBJECTIVE: This research aims to develop and evaluate a nanogel formulation loaded with khellin for the effective treatment of psoriasis. METHODS: Khellin nanogel was prepared using the self-assembly method with a synthesized gelatin- pluronic copolymer. The novel formulation was characterized via size, size distribution, encapsulation efficiency, in vitro release, and ex vivo skin deposition. RESULTS: The final nanogel formulation had an average size of 119.6 nm, a polydispersity index of 0.248 and an excellent encapsulation efficiency of 88%. In vitro drug release study demonstrated that nanogels showed a great accelerated drug release profile by releasing khellin within 2 hours, which is suitable for photochemotherapy applications. In addition, khellin-loaded nanogel formulation had 1.7 times better skin deposition potential than the control gel formulation. CONCLUSION: The prepared nanogel formulation provides a high potential to be an ideal drug delivery system of khellin in combination with phototherapy for more efficient psoriasis treatment.
Network Pharmacology Analysis and Experimental Verification of Weinaian Capsule for Treating Gastric Cancer.
Cheng Q, Li X, Shen L … +1 more , Yang T
Curr Pharm Biotechnol · 2026 · PMID 40325807 · Publisher ↗
BACKGROUND: Traditional Chinese medicine has been widely used to treat gastric cancer, but the effect of the Weinaian capsule on gastric cancer is still unclear. OBJECTIVE: This study aimed to find the potential therapeu...
BACKGROUND: Traditional Chinese medicine has been widely used to treat gastric cancer, but the effect of the Weinaian capsule on gastric cancer is still unclear. OBJECTIVE: This study aimed to find the potential therapeutic targets and pharmacological mechanisms of Weinaian capsule in gastric cancer. METHODS: We employed the network pharmacological analysis to find the therapeutic targets. Firstly, we searched the bioactive components of Weinaian capsule in TCMSP and the Swiss database. We downloaded disease gastric cancer targets from the GeneCards database and used the Venn diagram to identify common targets for disease and drugs. Then, we performed GO and KEGG pathway enrichment analyses, used the Cytoscape software to screen core targets and components, and constructed a drug-disease-target network. In addition, visual molecular docking and molecular dynamics simulation of targets and components with strong affinity were performed. Finally, we verified the effect of the drug on cell proliferation and metastasis using CCK8, clonal formation, and wound healing assays, and investigated the molecular mechanism by qRT-PCR. RESULTS: A total of 33 bioactive components were procured; 128 common targets for gastric cancer and drugs were screened. The GO and KEGG pathway enrichment analyses showed the PI3K-AKT pathway to be at the top. The core target AKT1 and the core component isorhamnetin exhibited the strongest molecular binding force and good binding stability. Compared to the control group, Weinaian capsule group inhibited gastric cancer cell proliferation and migration by down-regulating the expressions of PI3K and AKT. CONCLUSION: Weinaian capsule inhibited cell proliferation and metastasis by affecting the PI3K-AKT pathway in gastric cancer.
Unveiling the Role of Immune Cells and Plasma Metabolites in Breast Cancer Risk: A Mendelian Randomization and Mediation Analysis.
Li Y, Zhu Y, Gong K … +3 more , Wang Y, Huang Y, Hao W
Curr Pharm Biotechnol · 2025 May · PMID 40325806 · Publisher ↗
BACKGROUND: Breast cancer (BC) is the most common cancer worldwide, yet identifying effective therapeutic targets continues to pose challenges. To understand the biological mechanisms driving BC and uncover potential the...
BACKGROUND: Breast cancer (BC) is the most common cancer worldwide, yet identifying effective therapeutic targets continues to pose challenges. To understand the biological mechanisms driving BC and uncover potential therapeutic strategies, we performed a comprehensive Mendelian randomization (MR) analysis. The objective of this study is to investigate the causal relationships between immune cell phenotypes and BC risk, with a focus on identifying intermediary metabolites involved in these processes. METHODS: We conducted MR analysis using genome-wide association study (GWAS) data from publicly available databases, focusing on 731 immune cell traits (n = 3757), 1400 plasma metabolites (n = 8299), and breast cancer (n case = 6188, n control = 182,678). We used a two-step MR approach to examine the potential intermediary role of plasma metabolites in the immune cell-BC relationship. The research employs the inverse variance weighting (IVW) method as its primary approach. To assess potential sources of bias, such as horizontal pleiotropy and heterogeneity, we employed the MR Egger intercept test and the Cochran's Q test, respectively. These rigorous analytical approaches ensured the robustness of our findings. Furthermore, Bayesian colocalization was employed to enhance the accuracy of causal inference and reduce false positives. RESULTS: The IVW method of reverse MR analysis revealed a causal relationship between 20 immune cell traits and BC. Notably, our analysis identified three plasma metabolites as potential mediators in the causal link between immune cells and BC. In particular, vanillic acid glycine partially mediated the relationship between CD28+ CD45RA- CD8dim %CD8dim cells and BC. This suggests that vanillic acid glycine may act as a molecular link, modulating immune cell functions that contribute to BC. Additionally, the pyruvate to N-acetylneuraminate ratio exhibited negative mediation effects involving IgD- CD38dim AC, HLA DR on DC, CD8dim NKT %T cells, and CCR2 on monocytes. The negative mediation implies that this metabolite might inhibit certain immune cell behaviors that would otherwise promote cancer progression. Furthermore, cysteinylglycine disulfide partially mediated the relationship between CD8 on TD CD8br cells and BC, suggesting its involvement in the modulation of CD8 +T cell responses in BC. Key immune cell phenotypes, such as CCR2 on monocytes (odds ratio, ORIVW = 0.969; 95% CI: 0.943-0.996; p = 0.027), IgD- CD38dim AC cells (ORIVW = 1.100; 95% CI: 1.023-1.183; p = 0.009), were highlighted for their significant roles in BC progression. CONCLUSION: This study shows that vanillic acid glycine levels, the pyruvate to N-acetylneuraminate ratio, and cysteinylglycine disulfide levels can act as mediators in reducing breast cancer risk. These findings support the idea that metabolic pathways and metabolites are crucial in cancer progression, offering insights into potential biomarkers for early detection, treatment assessment, and recurrence prediction, thus paving the way for more personalized clinical approaches.
The Biological Effects of Nano-Curcumins against Drugs and Chemicals-Induced Nephrotoxicity: A Systematic Review.
Beigi F, Jouneghani AS, Heidari-Soureshjani S … +2 more , Sherwin CM, Mohajeri S
Curr Pharm Biotechnol · 2025 Apr · PMID 40325524 · Publisher ↗
INTRODUCTION/OBJECTIVE: Drug and chemical nephrotoxicity is a common cause of kidney disorders. This systematic review aimed to evaluate the recent progress in applying nanocurcumins (nano-CURs) to prevent and mitigate d...
INTRODUCTION/OBJECTIVE: Drug and chemical nephrotoxicity is a common cause of kidney disorders. This systematic review aimed to evaluate the recent progress in applying nanocurcumins (nano-CURs) to prevent and mitigate drug and chemical-induced nephrotoxicity, highlighting their underlying protective mechanisms and therapeutic potential. METHODS: A comprehensive search of experimental and clinical studies was conducted in various databases, including Web of Science, PubMed/MEDLINE, Scopus, Embase, and Cochrane Library. The studies were analyzed for improvements in bioavailability, mechanisms of action, and outcomes in reducing kidney damage. After extracting the data and entering it into an Excel sheet, the essential information and the related knowledge on consequences and mechanisms were collected. The collected information was discussed and analyzed. RESULTS: The antioxidant property of nano-CURs in dealing with nephrotoxicity is one of their most critical nephroprotective properties. They also exhibit potent anti-inflammatory, antiapoptotic, and anti-pyroptotic effects. Moreover, nano-CURs improve mitochondrial function, modulate kidney biochemical markers, modulate electrolyte imbalance, reduce endoplasmic reticulum (ER) stress, and improve kidney histopathological changes and autophagy, offering protection against nephrotoxicity induced by various drugs and chemicals. Nano-CURs significantly improve histopathological changes. Animal models have demonstrated reduced oxidative stress, inflammation, and apoptosis, causing improved renal function and histological outcomes. CONCLUSION: Nano-CURs have shown promising nephroprotective effects in experimental studies. However, these results have not been significant in clinical trial studies. Future research should focus on clinical trials and optimizing formulations for broader therapeutic applications.
Clinical Diagnosis and Treatment System for Neurological Psychological Gastrointestinal Diseases Based on Multimodal Artificial Intelligence and Immunology.
Li L, Jiang J, Guo L … +4 more , Santos J, González AM, Li S, Qin Y
Curr Pharm Biotechnol · 2025 Apr · PMID 40304348 · Publisher ↗
OBJECTIVE: To predict and assist in the treatment of colorectal cancer. BACKGROUND: Precision medicine systems can provide strategy optimization for the diagnosis and treatment of colorectal cancer to meet the needs of c...
OBJECTIVE: To predict and assist in the treatment of colorectal cancer. BACKGROUND: Precision medicine systems can provide strategy optimization for the diagnosis and treatment of colorectal cancer to meet the needs of clinical pricing institutions. AIM: To design an artificial intelligence multimodal gastrointestinal disease clinical information system based on neuroimmune gene regulation. METHOD: The system includes the use of cell gene expression levels to predict the 5-year survival rate of cancer patients, and the development of disease incidence rate prediction models based on immune cell status and living habits in somatic cell testing. The biological mechanism of feature selection in survival prediction systems was elucidated using single-cell sequencing technology, and this mechanism was analyzed in depth using molecular simulation techniques. Based on NCAM1 and CADM1 genes, biological activation pathway analysis was conducted to explore the biological mechanism of their synergistic immune genome regulation of gastrointestinal tumor proliferation. RESULT: The accuracy of each model is higher than 0.70. The experimental credibility is high. CONCLUSION: The research team conducted a detailed analysis of the biological characteristics of AI algorithms and reached a consensus with clinical experts. The ethical approval number of Chifeng Cancer Hospital is 202401, which has been reported by the World Health Organization.
Sirtuins in Osteosarcoma: Cracking the Code and Opening Up New Treatment Options.
Zhao Y, Han Y, Wang B … +1 more , Wang T
Curr Pharm Biotechnol · 2025 Apr · PMID 40289979 · Publisher ↗
Osteosarcoma (OS) is a frequent primary malignant bone tumor that primarily affects adolescents and the elderly, and it is prone to metastasis and recurrence. The prognostic status of metastatic and recurrent OS has rema...
Osteosarcoma (OS) is a frequent primary malignant bone tumor that primarily affects adolescents and the elderly, and it is prone to metastasis and recurrence. The prognostic status of metastatic and recurrent OS has remained stagnant over the past decades despite the availability of an extensive range of chemotherapy drugs in the clinic. To increase the overall survival and quality of life of patients with osteosarcoma, new therapeutic approaches must be developed immediately. In recent years, sirtuins (SIRT1-7) have garnered a lot of attention as researchers investigate the mechanisms underlying OS development and look for efficient treatment approaches. The nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylases (HDACs) that make up the sirtuin family are engaged in several biologically controlled processes, including proliferation, invasion, metastasis, apoptosis, autophagy, and chemotherapy resistance. Despite their significance in cancer having been avidly studied for decades, their specific functions and mechanisms of action are not yet clear due to limited reports. This review will summarize the current research status and look forward to the directions and prospects of its application in osteosarcoma research, aiming to open up new avenues for the treatment and study of osteosarcoma.
A Baicalin-Targeted ZHX2/MMP14 Axis Attenuates Cirrhotic Portal Hypertension.
Wang H, Ma J, Liu J … +3 more , Liu X, Cai X, Chang Y
Curr Pharm Biotechnol · 2025 Apr · PMID 40277105 · Publisher ↗
BACKGROUND: Given the high mortality associated with Cirrhotic Portal Hypertension (CPH) worldwide, this study investigates the mechanism by which baicalin (BA), known for its beneficial effects on cirrhosis, alleviates...
BACKGROUND: Given the high mortality associated with Cirrhotic Portal Hypertension (CPH) worldwide, this study investigates the mechanism by which baicalin (BA), known for its beneficial effects on cirrhosis, alleviates CPH. METHODS: The CPH model was established in Sprague-Dawley (SD) rats, followed by 4-week oral administration of 30 and 60 mg/kg/day BA. SD rats were randomly assigned to four groups (n=6/group): Con, Model, BA-30, and BA-60. Portal vein smooth muscle cells (PVSMCs, extracted from SD rats, n=6) were incubated with 5, 10 and 20 μmol/L BA. The levels of liver function indicators and von Willebrand factor (vWF) were determined by biochemical and immunohistochemical analyses, respectively. The portal pressure (PP) was examined. The liver fibrosis was detected by Sirius red staining. The levels of fibrosis-, angiogenesis- and proliferation- related indicators, zinc fingers and homeoboxes 2 (ZHX2), and matrix metallopeptidase 14 (MMP14) were quantified by Western blot. The levels of and interaction between ZHX2 and MMP14 were separately measured by quantitative real-time polymerase chain reaction (qRTPCR) and luciferase reporter assay. The proliferation and migration of PVSMCs were assessed by EdU staining and scratch test, respectively. RESULTS: BA up-regulated ZHX2 and down-regulated MMP14 (P<0.001). BA concentrationdependently suppressed liver fibrosis, PP, and angiogenesis in the liver tissue, as well as PVSMC proliferation and migration, while enhancing liver function (P<0.05). Further, according to the GRNdb database and luciferase reporter assay, ZHX2 is bound with the promoter of MMP14. ZHX2 could suppress the MMP14 level (P<0.001). ZHX2 silencing reversed the effects of BA treatment on the proliferation and migration of PVSMCs, whereas MMP14 silencing could further offset the role of ZHX2 silencing in the BA-treated PVSMCs (P<0.05). CONCLUSION: BA up-regulates ZHX2 to reduce the level of MMP14 and alleviate CPH. Understanding the mechanisms of BA in CPH may provide a foundation for novel interventions to attenuate CPH.
Selenium Alleviates Oxidative Stress and Inflammation to Promote Postpartum Uterine Recovery via GPX1/GPX4/NRF2 Pathway in Mice.
Li X, Li P, Wang P
Curr Pharm Biotechnol · 2025 Apr · PMID 40277104 · Publisher ↗
BACKGROUND: Selenium is an important trace element that plays crucial roles in metabolism, immune function, and antioxidant defense. As an antioxidant, selenium helps to alleviate postpartum uterine inflammation and prom...
BACKGROUND: Selenium is an important trace element that plays crucial roles in metabolism, immune function, and antioxidant defense. As an antioxidant, selenium helps to alleviate postpartum uterine inflammation and promotes uterine recovery. However, the exact mechanism underlying the role of selenium in postpartum uterine recovery is not fully understood. OBJECTIVE: This study aimed to identify the underlying mechanism and examine how selenium enhances postpartum uterine healing. METHODS: Female ICR mice aged 8 weeks were classified into five groups: control, postpartum model, low-dose selenium (100 nm), medium-dose selenium (200 nm), and high-dose selenium (400 nm). Endometrial morphology was evaluated by hematoxylin and eosin (H&E) staining. Oxidative stress markers, including superoxide dismutase (SOD), catalase (CAT), glutathione peroxidase (GPX), and malondialdehyde (MDA), and inflammatory factors, including tumor necrosis factor-alpha (TNF-α) and interleukin-1 beta (IL-1β), were measured using commercially available kits. GPX1, GPX4, and nuclear factor erythroid 2-related factor 2 (NRF2) expression were determined using real-time PCR and WB. RESULTS: We found damage and bleeding points in the endometrium and destruction of the ultrastructure of endometrial cells in the postpartum model group; however, mice treated with a high dose (400 nm) of selenium showed alleviated levels of pathological alteration in the endometrium. In addition, the levels of MDA in the postpartum mice group increased, while the SOD, CAT, and GPX levels decreased; however, changes in these oxidative stress markers were reversed after selenium treatment. For inflammatory factors, high levels of TNF-α and IL-1β were observed in postpartum mice, whereas they were decreased in selenium-treated groups. GPX1, GPX4, and NRF2 expression were reduced in postpartum model mice, but upregulated in selenium- treated mice. CONCLUSION: Selenium supplementation ameliorated postpartum uterine oxidative stress and inflammation and promoted uterine recovery via the GPX1/GPX4/NRF2 pathway in mice.
Anti-Cancer Properties and Mechanistic Insights of Dihydroquercetin.
Zhang C, Zeng Y, Wu B … +4 more , Wang L, Wu P, Shen A, Wang L
Curr Pharm Biotechnol · 2025 Apr · PMID 40277103 · Publisher ↗
Dihydroquercetin (DHQ), also known as taxifolin, is a naturally occurring flavonoid compound that serves as an active pharmaceutical ingredient. It is commercially available in the form of dietary supplements. As the red...
Dihydroquercetin (DHQ), also known as taxifolin, is a naturally occurring flavonoid compound that serves as an active pharmaceutical ingredient. It is commercially available in the form of dietary supplements. As the reduced form of quercetin, DHQ contains five phenolic hydroxyl groups. This compound is capable of chelating transition metal ions, thereby effectively scavenging free radicals and detoxifying harmful substances while modulating enzyme activities. Consequently, DHQ exhibits potent antioxidant, anti-inflammatory, antiviral, and antibacterial properties. Given its significant pharmacological potential, DHQ exhibits anti-tumor activity against various malignant tumors, including breast cancer, gastric cancer, hepatocellular carcinoma, colonic neoplasms, melanoma, and prostate cancer. DHQ inhibits tumor occurrence and progression by regulating multiple signaling pathways, such as wnt/β-catenin, phosphoinositide 3-kinase (PI3K)/protein kinase B (Akt), mammalian target of rapamycin (mTOR), transforming growth factor-beta (TGF-β), nuclear factor kappa-light-chain-enhancer of activated B cells (NF- κB), and mitogen-activated protein kinase (MAPK). The anti-tumor mechanisms of DHQ include inhibition of cell proliferation, invasion, and migration; induction of cell cycle arrest, activation of autophagy, apoptosis, epigenetic modification, suppression of epithelial-mesenchymal transition (EMT), enhancement of chemotherapy efficacy, and augmentation of immune function. In particular, DHQ potentiates the efficacy of chemotherapy drugs and augments immune function. Based on a systematic review of the pharmacological properties and anti-tumor mechanisms of DHQ across multiple malignant tumors, we conclude DHQ to be a promising natural compound with significant potential for anti-tumor therapy.
Safflower Extract Mitigates MIRI in Rats by Modulating TLR-4/NF-κB Signaling Pathway, Demonstrating Protective Effects.
Deng M, Yang J, Julaiti A … +3 more , Dong Y, Deng Y, Wang Z
Curr Pharm Biotechnol · 2025 Apr · PMID 40277102 · Publisher ↗
BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) exacerbates tissue damage following the restoration of coronary blood flow after ischemia. The TLR-4/NF-κB signaling pathway plays a crucial role in the pathogene...
BACKGROUND: Myocardial ischemia-reperfusion injury (MIRI) exacerbates tissue damage following the restoration of coronary blood flow after ischemia. The TLR-4/NF-κB signaling pathway plays a crucial role in the pathogenesis of MIRI. This study investigated the therapeutic efficacy of safflower extract in mitigating MIRI and its modulation of TLR-4/NF-κB signaling in rats. METHODS: Adult male Sprague-Dawley rats were subjected to 30 minutes of myocardial ischemia followed by 2 h of reperfusion. Safflower extract was administered intravenously at doses of 2, 4, and 8 mg/kg 15 minutes before ischemia and 1 minute before reperfusion. Infarct size was assessed using TTC staining. Serum levels of creatine kinase (CK) and lactate dehydrogenase (LDH) were measured. Pro-inflammatory cytokines (IL-1β, IL-6, and TNF-α) were quantified using ELISA. TLR-4 and NF-κB mRNA and protein expression were evaluated using qRT-PCR and western blotting, respectively. Histopathological changes were assessed using H&E staining. RESULTS: Safflower extract effectively reduced myocardial infarct size in a dose-dependent manner, with the highest dose providing the greatest benefit. Treatment with safflower extract significantly lowered the elevated levels of serum CK and LDH caused by ischemia-reperfusion (I/R) injury, bringing these biochemical markers closer to normal values. In addition, safflower extract decreased the levels of pro-inflammatory cytokines IL-1β, IL-6, and TNF-α in myocardial tissue, showing a clear dose-response relationship. Analysis through qRT-PCR and western blot confirmed that safflower extract downregulated the expression of TLR4 and NF-κB at both the transcriptional and protein levels. Histological studies further supported these findings, demonstrating that safflower extract improved myocardial tissue architecture, maintained cardiomyocyte structure, and reduced inflammatory cell infiltration. CONCLUSIONS: Safflower extract provides significant cardioprotection against MIRI by modulating the TLR-4/NF-κB-mediated inflammatory response. These findings suggest that safflower extract may be a potential therapeutic agent for mitigating the effects of myocardial ischemiareperfusion injury.
Potential Pharmacological Ability of a Novel Marine Polysaccharide Extracted from Tunisian Green Algae to Accelerate Dermal Wound Healing in Rats.
Kraiem M, Eleroui M, Boujhoud Z … +5 more , Ajala M, Bouhamed M, Hilali A, Kallel H, Ben Amara I
Curr Pharm Biotechnol · 2025 · PMID 40277058 · Publisher ↗
BACKGROUND: Bacterial infection and oxidative stress generation are significant obstacles to dermal wound healing. The present study undertakes the isolation of a sulfated polysaccharide from the Tunisian green algal na...
BACKGROUND: Bacterial infection and oxidative stress generation are significant obstacles to dermal wound healing. The present study undertakes the isolation of a sulfated polysaccharide from the Tunisian green algal named PCA. METHODS: The polysaccharide PCA was structurally characterized using Fourier Transformed Infrared (FT-IR), and monosaccharide analysis was carried out by HPLC-FID X-ray diffraction (XRD) and Scanning Electron Microscopy (SEM). The antioxidant potential of polysaccharides extracted from the was evaluated in vitro using various antioxidant assays, and the antibacterial activity of PCA against four Gram-negative bacteria was estimated. The wound healing capacity of PCA was evaluated in vivo using an excision wound model in rats. RESULTS: FT-IR spectra revealed the characteristic bands of polysaccharides. HPLC-FID revealed a heteropolysaccharide composed of arabinose, glucose, glucuronic acid, and galactose units. Indeed, the X-ray diffraction revealed a semi-crystalline structure of PCA. The obtained data showed a strong antioxidant capacity and an interesting antibacterial activity against four-gram negative bacteria , and . These biological data strongly support the beneficial effects of PCA in accelerating wound healing in rats. The study on rats demonstrated that PCA significantly accelerated the wound healing process over an 11-day treatment period. The application of PCA on wounds led to enhanced collagen fiber synthesis, as evidenced by histological staining, which showed increased collagen deposition at the wound site. Additionally, PCA treatment resulted in faster wound closure, with measurements showing a marked reduction in wound size compared to control groups. CONCLUSION: The present study highlights the promising pharmacological effects of PCA, suggesting its potential application in wound dressings due to its robust antioxidant, antibacterial, and wound-healing properties.
Challenges and Pathways in Regulating Next-Gen Biological Therapies.
Agrawal S, Vaidya S, Patel J … +2 more , Jirvankar P, Gurjar P
Curr Pharm Biotechnol · 2025 Apr · PMID 40277057 · Publisher ↗
BACKGROUND: Current medicine could benefit from gene and cell therapies for genetic defects, cancer, and degenerative disorders. These therapies modify genetic material or biological components. CRISPR-Cas9 gene editing,...
BACKGROUND: Current medicine could benefit from gene and cell therapies for genetic defects, cancer, and degenerative disorders. These therapies modify genetic material or biological components. CRISPR-Cas9 gene editing, stem cell, and CAR-T treatments are examples. Complex products need rigorous regulations to ensure quality, efficacy, and patient safety. OBJECTIVES: This paper discusses international gene and cell-based treatment regulatory regimes, highlighting key issues and recent developments. It also includes gene and cell-based therapy classes and mechanisms. METHOD: The publications on gene and cell therapy challenges and their regulatory approvals in the US, Europe, Japan, Australia, Brazil, Canada, and China were collected over the last 20 years from PubMed, Scopus, and Google Scholar and analyzed to determine the differences. RESULTS: Gene treatments correct genetic defects or disease processes by adding, removing, or changing cell genetic information. In contrast, cell-based therapies restore damaged tissues with modified or unmodified cells. Highly customized and patient-specific drugs make regulatory monitoring challenging. US FDA CBER controls gene and cell-based therapies. Before clinical trials, these biologic drugs must file BLAs for market approval and INDs. DISCUSSION: FDA's Breakthrough Therapy and Regenerative Medicine Advanced Therapy (RMAT) designations accelerate biological development. The EMA oversees EU Advanced Therapy Medicinal Products. ATMP quality, safety, and efficacy are CAT's top priorities. The Conditional Marketing Authorization process expedites access to life-threatening disease medicines while the MAA regulates them. Japan's PMDA's Conditional Time-Limited Approval for regenerative medicines provides early commercialization and rigorous post-market supervision. Similarly, each country has adopted some ways to expedite the approval of biologicals. Geneediting drugs require specialized methods, long-term follow-up, and better safety to avoid offtarget effects. GMPs ensure production uniformity, sterility, and safety, complicating manufacturing and quality control. CONCLUSION: The review concludes that there is a need for worldwide regulatory harmonization and regulatory framework developments, including R.W.E., adaptive pathways, and personalization of biologics.
Predicting Inhibitor Development in Hemophilia 'A' using Machine Learning: A Comprehensive Approach to Data Preprocessing, Balancing, and Biomarker Identification Using AI on the CHAMP Dataset.
Singh VK, Singh MP
Curr Pharm Biotechnol · 2025 · PMID 40264326 · Publisher ↗
BACKGROUND: Hemophilia 'A' (HA) is a genetic blood disorder characterized by a deficiency of Factor VIII (FVIII), with treatment often triggering the development of neutralizing antibodies (inhibitors) to FVIII. Predicti...
BACKGROUND: Hemophilia 'A' (HA) is a genetic blood disorder characterized by a deficiency of Factor VIII (FVIII), with treatment often triggering the development of neutralizing antibodies (inhibitors) to FVIII. Predicting the development of these inhibitors is crucial for clinical applications but presents significant computational challenges due to data imbalance, skewed data, and inadequate data sanitization. OBJECTIVES: This study aimed to develop a machine-learning/AI approach to find biomarkers and predict the development of inhibitors to Factor VIII in patients with Hemophilia 'A,' addressing the challenges associated with data imbalance and enhancing prediction accuracy. METHODS: The data were sanitized and encoded for prediction, and the Random Over-sampling (ROS) technique was employed to resolve data imbalance in the CHAMP dataset. Several machine- learning classification models, including Random Forest, XG Boost, Cat Boost, Logistic Regression, Gradient Boosting, and Light GBM, were utilized. Hyperparameters were tuned using GridSearchCV optimization with a stratified k-fold approach. The performance of the models was evaluated based on accuracy, precision, recall, and F1 scores. The Random Forest model was further analyzed using an explainable AI (XAI) tool known as SHAP (SHapley Additive exPlanations) to identify the variables influencing model performance. RESULTS: The Random Forest model outperformed other classifiers, achieving a mean accuracy of 97.37%, along with closely aligned precision, recall, and F1 scores. The XAI tool SHAP facilitated the ranking of variables Clinical Severity, Variant Type, Exon, HGVS cDNA, hg19 Coordinates, and others according to their impact on the model's predictions. Additionally, the study identified biomarkers associated with FVIII inhibition. CONCLUSION: This study presents a breakthrough in the early prediction of inhibitor development in Hemophilia 'A' patients, paving the way for personalized and effective treatment programs. The integration of the preprocessing pipeline, Random Forest model, and SHAP analysis offers a novel solution for guiding treatment strategies for HA patients, which could significantly enhance the development of targeted and effective therapies.
Microbial Influences: The Microbiome's Impact on Pancreatic Cancer Development and Progression.
Fakruddin M, Chowdhury Z, Suprova SN … +6 more , Ul Islam B, Sultana Jime J, Bulbul N, Anam MB, Bin Mannan S, Shishir MA
Curr Pharm Biotechnol · 2025 Apr · PMID 40257025 · Publisher ↗
Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges due to its dense stromal environment, which impedes treatment efficacy. Recent molecular and phenotypic analyses have enhanced our understanding of...
Pancreatic ductal adenocarcinoma (PDAC) presents significant challenges due to its dense stromal environment, which impedes treatment efficacy. Recent molecular and phenotypic analyses have enhanced our understanding of PDAC, driving the development of targeted therapies. Emerging research highlights the crucial role of the pancreatic tumor microbiome in PDAC initiation and progression. However, the specific mechanisms influencing the tumor microenvironment (TME) and systemic immunity remain incompletely understood. Studies have elucidated various genetic mutations, signaling pathways, and cellular interactions driving PDAC progression, aiding the development of targeted therapies. Despite these advances, overall survival rates for PDAC patients remain low, necessitating novel therapeutic strategies. Therapeutic strategies targeting the microbiome hold significant potential. Therapeutic strategies aimed at modulating microbiomes demonstrate significant potential for treating diseases and enhancing human well-being. Early research indicates that manipulating the microbiome could alter the TME to enhance the efficacy of existing treatments and lead to new therapeutic modalities. Modulating microbiomes might improve the delivery and effectiveness of chemotherapeutic agents or sensitize the tumor to immunotherapy, potentially revolutionizing PDAC treatment paradigms. Microbes can indirectly contribute to pancreatic cancer by inducing chronic inflammation and immune dysregulation. Microbes create a pro-inflammatory environment conducive to cancer development. This persistent inflammation can lead to genetic mutations and a suppressed immune response, fostering an environment where cancer cells can thrive. This review synthesizes current evidence on how the microbiome influences PDAC development and progression, emphasizing its potential for early disease detection and novel therapeutic strategies. Early detection, particularly in premalignant conditions such as chronic pancreatitis and intraductal papillary mucinous neoplasm (IPMN), is crucial for improving patient outcomes through timely intervention.
A Comprehensive 4-layered Pharmacogenomics Analysis of the Genetic Addiction Risk Severity (GARS) Test: Strong Genetic Evidence Supporting GARS as a Novel Personalized Pre-addiction Assessment Tool in the Opioid Crisis Era.
Sharafshah A, Lewandrowski KU, Elman I … +22 more , Baron D, Thanos PK, Hanna C, Gold MS, Badgaiyan RD, Cadet JL, Modestino EJ, Braverman ER, Dennen CA, Makale M, Sunder K, Murphy KT, Bowirrat A, Pinhasov A, Gondre-Lewis M, Gardner E, Sipple D, Jafari N, Zeine F, Khalsa J, Fiorelli RKA, Blum K
Curr Pharm Biotechnol · 2025 · PMID 40247807 · Publisher ↗
BACKGROUND: Overdose involving opioids is the black heart of the addiction crisis. "Pre-addiction," as an encouraging concept by NIDA and NIAAA, seems best captured with the construct of dopamine dysregulation. Referring...
BACKGROUND: Overdose involving opioids is the black heart of the addiction crisis. "Pre-addiction," as an encouraging concept by NIDA and NIAAA, seems best captured with the construct of dopamine dysregulation. Referring to the abundant publications on "Reward Deficiency Syndrome" (RDS), Genetic Addiction Risk Score (GARS) test, RDSQ29, and KB220, Pre-addiction can be referred to as "reward dysregulation" as a suitable suggestion. The hypothesis is that the true phenotype is RDS, and other behavioral disorders are endophenotypes where the genetic variants play important roles, specifically in the Brain Reward Cascade (BRC). METHODS: This study tested the pharmacogenomics of the GARS panel by a multi-model in silico investigation in four layers: 1) Protein-Protein Interactions (PPIs); 2) Gene Regulatory Networks (GRNs); 3) Disease, drugs and chemicals (DDCs); and 4) Gene Coexpression Networks (GCNs). RESULTS: All in silico findings were combined in an Enrichment Analysis for 59 refined genes, which represented highly significant associations of dopamine pathways in the BRC and supported our hypothesis. CONCLUSION: This paper provides scientific evidence for the importance of incorporating GARS as a predictive test to identify Pre-addiction, introduce unique therapeutic targets assisting in the treatment of pain, drug dosing of prescription pharmaceuticals, and identify the risk for subsequent addiction early in -life.
siRNA Therapeutics in Lymphoma: Gene Targets, Delivery Strategies, and Synergy with Chemotherapy.
Ikebunwa O, Turenko V, Uchendu I … +3 more , Kovchina V, Bagaev D, Smirnov V
Curr Pharm Biotechnol · 2025 Apr · PMID 40237047 · Publisher ↗
Lymphoma is a type of cancer that arises from the lymphatic system, which involves the uncontrollable proliferation of abnormal lymphocytes. Traditionally, lymphoma is classified into Hodgkin and non-Hodgkin lymphoma. To...
Lymphoma is a type of cancer that arises from the lymphatic system, which involves the uncontrollable proliferation of abnormal lymphocytes. Traditionally, lymphoma is classified into Hodgkin and non-Hodgkin lymphoma. To date, chemotherapy remains one of the most common treatments for lymphoma. Notwithstanding the level of efficacy achieved in the use of chemotherapy, the toxicity and drug resistance by cancer cells have been a major obstacle in the treatment of lymphoma. Currently, researchers are exploring the use of siRNA to specifically target and knock down carcinogenic genes involved in lymphoma. The ability of siRNA to target specific genes makes it a good potential substitute for chemotherapeutic agents. Additionally, various delivery systems have also been developed over the years to help mitigate the challenges involved in siRNA delivery to their target genes, which include but are not limited to offtarget effects and systemic breakdown by nucleases. However, there are still many setbacks that need to be resolved to get the desired standard in using only siRNA for lymphoma treatment. Combinations of siRNA with chemotherapy drugs are successful against a variety of molecular targets and can make cancer cells more susceptible to treatment. Therefore, the use of chemotherapy and siRNA might provide the much-needed solution for lymphoma treatment, with reduced toxicity and increased efficacy. Considering the fact that some delivery systems have been developed for the co-delivery of chemotherapeutic agents and siRNA for treating cancers, exploring this option in lymphoma treatment would be a great option towards the right direction and requires better knowledge and development of siRNA therapeutics.
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