Current pharmaceutical biotechnology最新文献

PIWI-interacting RNAs (piRNAs), a class of small non-coding RNAs originally identified in germ cells, are now increasingly recognized as pivotal regulators of gene expression in somatic tissues, including the cardiovascular system. Cardiovascular diseases (CVDs) remain the leading global cause of morbidity and mortality, yet sensitive and specific molecular biomarkers and effective RNA-based therapeutic targets are still lacking. However, compared to microRNAs and lncRNAs, the roles of piRNAs in CVD are only beginning to be elucidated, highlighting an important knowledge gap. The objective of this review was to synthesize current evidence on piRNA functions in cardiovascular biology, with emphasis on disease-specific mechanisms and translational implications. To achieve this, we conducted a literature search in PubMed and Web of Science databases (2015-2025) using the keywords "piRNA" OR "PIWIinteracting RNA" combined with "cardiovascular", "heart failure", "ischemia reperfusion", "myocardial infarction", "aortic valve", and "pulmonary hypertension". This review has not only summarized existing findings, but also highlighted emerging opportunities and challenges for advancing piRNA-based diagnostics and therapeutics in cardiovascular medicine.

Introduction/objective: Cervical cancer (CC) remains a major global health problem, especially in advanced stages. Systemic inflammatory markers such as the neutrophil-tolymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR), and systemic immune-inflammation index (SII) have been proposed as prognostic indicators. This study evaluated treatment-related alterations in these markers and their associations with clinical factors.

Methods: In this prospective study, 106 women with FIGO stage IB-IVA CC treated with dCRT were analyzed. Peripheral blood was collected one day before treatment and within three days after teletherapy. Inflammatory indices were derived from complete blood counts, and tumor volumes were assessed by MRI. Associations with clinical and treatment parameters were explored using appropriate statistical methods.

Results: After teletherapy, NLR increased significantly (median 4.86 vs. 3.31, p = 0.022), PLR rose markedly (377.5 vs. 198.8, p < 0.001), and LMR decreased (1.35 vs. 2.49, p < 0.001). SII changes were not significant. Baseline indices correlated with pre-treatment tumor volume, while post-therapy NLR and LMR were associated with post-teletherapy tumor volume but not with radiation dose, histological grade, or FIGO stage. An exploratory Kaplan-Meier analysis suggested poorer outcomes with elevated NLR and PLR, although differences were not statistically significant.

Discussion: Observed alterations in NLR, PLR, and LMR suggest these markers reflect tumor burden and immune response dynamics during dCRT.

Conclusion: NLR, PLR, and LMR undergo significant changes during dCRT, largely reflecting tumor burden rather than treatment parameters, supporting their role as dynamic biomarkers in CC.

Natural killer (NK) cells are essential cytotoxic effectors of the innate immune system with significant therapeutic advantages in cancer immunotherapy, primarily due to their intrinsic MHC-unrestricted cytotoxicity and capacity for antigen-independent tumor recognition. Compared to T cell-based immunotherapies, NK cell-centered strategies facilitate precision immunotherapy through chimeric antigen receptor (CAR) engineering while demonstrating superior allogeneic compatibility. This inherent resistance to graft-versus-host disease (GVHD) circumvents the limitations of autologous cell sourcing and enables "off-the-shelf" therapeutic availability. This review systematically outlines the developmental biology and functional characteristics of NK cells, their diverse cellular origins, and the dynamic regulatory mechanisms governed by the balance of activating and inhibitory receptors. Furthermore, it highlights recent advances in the clinical translation of engineered NK cell therapies, including CAR-NK cells, and discusses their therapeutic applications in cancer treatment.

Introduction: The growing awareness regarding animal-derived content in pharmaceuticals has led to an increased demand for labeling of animal-derived ingredients. Multiplex qPCR can amplify more than one target gene by combining two or more primer sets in one reaction. Thus, this study focused on developing a universal forward primer and specific reverse primers targeting 16S rRNA for the simultaneous detection of Murine, Porcine, Canine, and Murine.

Methods: These primers were evaluated in silico, followed by in vitro optimization using intercalating dye-based qPCR for detecting the presence of these genes in total DNA extracted from food-based meat and pharmaceutical products.

Result: These primers successfully produced amplicons in multiplex qPCR with distinct melting temperatures. Additionally, the developed primers in multiplex qPCR were capable of identifying Murine, Canine, and Porcine DNA at concentrations of 10-100 pg with an efficiency of 90- 110%. Repeatability testing revealed a variance of less than 10% for both intra- and inter-assay. Furthermore, the new primer combination successfully detected DNA remnants in positive porcine pharmaceuticals and cosmetics.

Discussion: The developed primers were able to differentiate animal species concentrations found in pharmaceuticals and cosmetics with good repeatability. However, porcine peaks in sample analysis were still low due to the low yield of DNA extraction using a food-grade DNA extraction kit Conclusion: These results suggest that the new primer combination, consisting of the universal forward primer and species-specific reverse primers, has the potential to serve as an alternative assay for differentiating canine, porcine, and murine DNA using multiplex intercalating dyebased qPCR.

Introduction: Non-small cell lung cancer (NSCLC) is among the most aggressive malignancies threatening human health. Histone deacetylase inhibitors (HDACi) have been shown to suppress epidermal growth factor receptor (EGFR) signaling, making them promising candidates for NSCLC therapy. This study aimed to evaluate the effects of Entinostat on NSCLC.

Methods: The anti-proliferative effect of Entinostat was assessed using MTT assays, with four other HDAC inhibitors (the pan-HDAC inhibitor SAHA and selective HDAC inhibitors BRD73954, BG45, and NKL22) as controls. EGFR expression and phosphorylation of STAT3, AKT, and p38 were measured in vitro and in vivo via Western blot. Apoptosis was analyzed by flow cytometry, and expression of apoptosis regulators p53 and p21 was assessed by Western blot. The in vivo anti-tumor activity of Entinostat was evaluated using NSCLC xenograft models.

Results: Entinostat exhibited more potent anti-NSCLC activity than the other HDAC inhibitors in H460 and H1975 cell lines, with IC50 values of 0.69±0.03 μM and 0.20±0.01 μM, respectively. Western blot analysis demonstrated that Entinostat reduced EGFR expression and decreased phosphorylation of STAT3, AKT, and p38, indicating suppression of EGFR signaling both in vitro and in vivo. In xenograft models, treatment with 40 mg/kg Entinostat significantly inhibited tumor growth, though it also affected mouse body weight.

Conclusion: Entinostat demonstrates strong anti-NSCLC activity by suppressing EGFR expression and downstream signaling, highlighting its potential as a therapeutic agent.

Autoimmune diseases remain one of the top leading causes of morbidity and mortality globally. While several first-line therapies like corticosteroids, immunosuppressants, and DMARDs are proven effective, their prolonged use often leads to drug-induced complications. Researchers are increasingly drawn to natural compounds, which are more accessible, inexpensive, and safer. Among these interventions are flavonoids, which are natural polyphenols derived from plants. The goal of autoimmune disease treatment is to. Flavonoids such as quercetin, EGCG balance effector and regulatory immune function to prevent autoimmunity. Flavonoids such as quercetin, EGCG, and silymarin exert immunomodulatory, anti-inflammatory, and antioxidant activities in this context by inhibiting NF-κB signaling and downregulating proinflammatory cytokines such as IL-6 and TNF-α. For this reason, flavonoids have gained attention as promising adjuvants to conventional therapies, especially in preclinical studies. However, robust clinical evidence remains limited, and further trials are necessary to validate these therapeutic claims. In this review, we summarize the newest research on the specific molecular mechanisms underlying flavonoids' therapeutic effects and their clinical use in certain autoimmune diseases.

Background: The increasing prevalence of antibiotic-resistant bacteria necessitates exploring nanotechnology as a potential solution for microbial elimination.

Objectives: This study aimed to investigate the antimicrobial and antioxidant effects of silver nanoparticles synthesized using aqueous extract from the Ephedra gerardiana (E. gerardiana) plant (EG@AgNPs).

Methods: Optimal synthesis conditions, including silver nitrate concentration, time, and temperature, were determined. Characterization of EG@AgNPs was conducted, which was followed by antimicrobial assessment against eight bacterial strains and one fungal strain. Additionally, the antioxidant properties of EG@AgNPs were evaluated using the DPPH method.

Results: XRD analysis confirmed EG@AgNPs synthesis. DLS analysis revealed a hydrodynamic diameter of 22 nm. FT-IR analysis confirmed the presence of functional groups from the E. gerardiana plant extract in EG@AgNPs. FESEM and TEM images depicted spherical nanoparticles ranging in size from 10 to 20 nm. Antimicrobial investigations using the broth microdilution method demonstrated that E. gerardiana plant extract at 7.5 mg/ml inhibited only Streptococcus mutans and Candida albicans growth, with no antimicrobial effects observed at lower concentrations. However, EG@AgNPs significantly enhanced the antimicrobial properties of the E. gerardiana plant extract. Notably, these nanoparticles exhibited the most significant effect on E. coli and the least on S. salivaris, with MIC value of 125 and 2000 μg/ml, respectively. Furthermore, they inhibited C. albicans growth at a concentration of 62.5 μg/ml. An assessment of the antioxidant properties of EG@AgNPs indicated a significant increase in antioxidant activity.

Conclusion: The E. gerardiana plant extract has emerged as a promising option for silver nanoparticle synthesis. These nanoparticles have been found to exhibit potent antimicrobial properties against Gram-positive and Gram-negative bacterial species, as well as C. albicans. Additionally, they have demonstrated antioxidant properties.

The pharmaceutical industry is transforming with the advent of Industry 5.0, which is marked by integrating artificial intelligence (AI) into drug discovery and development. AI technologies, such as machine learning, deep learning, and natural language processing, revolutionize the traditional drug development pipeline by accelerating the identification of novel drug candidates, optimizing clinical trial designs, and personalizing therapies. Moreover, AI models enhance the prediction of drug efficacy, toxicity, and patient responses, minimizing the risk of failure of clinical trials. Nevertheless, despite these advancements, challenges remain in integrating AI into the pharmaceutical workflow, including data quality, regulatory concerns, and the need for interdisciplinary collaboration. This review explores the current state of AI applications in drug discovery, drug formulation and optimization, pharmacokinetics and pharmacodynamics, drug manufacturing and quality control, regulatory compliance and pharmacovigilance. Overall, AI is poised to redefine the landscape of drug discovery and development, fostering a new era of precision medicine and transforming patient outcomes globally, especially in the era of Industry 5.0.