Current pharmaceutical biotechnology最新文献

Introduction: This study aims to examine the impact of Rukangyin (RKY) and its components, LSQR and QTSS, on various cellular processes and signaling mechanisms in MDA-MB-231 triple-negative breast cancer (TNBC) cells.

Methods: Twenty-five Sprague-Dawley (SD) rats were randomly assigned to five groups according to the administered drugs, including the RKY group, LSQR group, QTSS group, fluorouracil group, and blank control group (n=5 in each group). The serum samples from each group were then used as a medicated medium for the culture of the TNBC cell line MDA-MB-231. Cell viability tests, apoptosis detection tests, and migration and invasion tests were used to evaluate the cytotoxicity of treated serum. YAP, TAZ, MST1, and LATS1 protein expression and phosphorylation were examined using conventional western blotting methods.

Results: RKY and its QTSS and LSQR components significantly inhibited cell growth and promoted apoptosis in MDA-MB-231 cells. RKY also significantly blocked cell motility with a comparable effect to that of fluorouracil. All serum groups suppressed YAP and TAZ expressions while increasing p-YAP, p-TAZ, MST1, and LATS1 levels, with RKY showing superior efficacy.

Discussion: In TNBC cells, RKY appears to enhance the tumor-suppressing signals of the Hippo signaling pathway via MST1, LATS1 activation, while restricting its pro-oncogenic action via YAP and TAZ blockade. However, in vivo and animal model experiments are required to confirm these findings.

Conclusion: RKY-medicated serum effectively inhibits growth, induces apoptosis, and reduces motility in the MDA-MB-231 cell line of breast cancer. This therapeutic potential of RKY on TNBC cells draws attention to the need for more investigations.

Introduction: Wilms tumor (WT) is a common pediatric kidney cancer with unclear molecular mechanisms driving its progression. Despite advancements in treatment, prognosis remains suboptimal for high-risk cases, highlighting the urgent need for novel biomarkers for early diagnosis and targeted therapies. In this study, we investigated the molecular underpinnings of WT by identifying key hub genes and evaluating their diagnostic and prognostic potential.

Methods: Differentially expressed genes (DEGs) were identified from Gene Expression Omnibus (GEO) datasets, and common genes were analyzed using protein-protein interaction (PPI) networks to find hub genes. Functional assays, including cell proliferation, colony formation, and wound healing, were performed to validate the hub genes. Prognostic value, miRNA interactions, and pan-cancer expression analysis were also conducted, along with drug sensitivity evaluation.

Results: Analysis of gene expression data from publicly available GEO datasets revealed that SLC12A3, ADH6, GSTM3, and CLCNKB hub genes were significantly dysregulated in WT. Receiver operating characteristic (ROC) curve demonstrated that these hub genes showed strong diagnostic potential, with high sensitivity and specificity in distinguishing WT from normal tissues. Additionally, the expression levels of these genes were closely associated with the overall survival of WT patients, indicating their prognostic significance. Furthermore, analysis of potential miRNA interactions revealed that specific miRNAs could regulate these hub genes, contributing to the pathogenesis of WT. Functional studies of SLC12A3 and ADH6 overexpression showed reduced cell proliferation, colony formation, and migratory capacity, suggesting their involvement in inhibiting tumor progression.

Conclusion: This study emphasizes the critical roles of SLC12A3, ADH6, GSTM3, and CLCNKB in WT and their potential as both diagnostic biomarkers and therapeutic targets in WT management.

Introduction: Cardiovascular diseases (CVDs) are the leading cause of death globally, often complicated by thromboembolic events. Plasmin, a key enzyme in fibrinolysis, is crucial for managing these conditions. Elevated or reduced plasmin levels can indicate thrombotic risks, making it a valuable diagnostic marker. Recent biotechnological advances have developed diagnostic kits to measure plasmin activity, aiding early detection and intervention. Fungal proteases, particularly from micromycetes, are emerging as promising agents in anticoagulant therapy. This study investigates three Aspergillus species - A. caespitosus, A. jensenii and A.neotritici - for their potential to produce novel biomedical components.

Methods: The fungi were cultured, and their proteolytic profiles were analyzed. Key findings include the identification of specific proteases with plasmin-like and protein C-activating activities. These enzymes were purified using isoelectric focusing and characterized through SDSPAGE and zymography.

Results: The study confirmed that A. jensenii, and A. neotritici produce proteases with plasminlike activity, with A. neotritici showing a single 35 kDa non-specific protease, and A. jensenii exhibiting two proteases (33 kDa and 100 kDa) in the acidic zone and one (110 kDa) in the neutral zone, the latter exhibiting specific chymotrypsin and plasmin-like activity.

Discussion: Among the studied strains, A. neotritici exhibited the fastest secretion of proteases with plasmin-like activity, making it a promising source of enzymes with potential clinical applications. In contrast, A. caespitosus and A. jensenii displayed more complex protease compositions, featuring multiple active enzymes. Notably, one of the A. jensenii proteases showed pronounced specificity toward chymotrypsin and fibrinolytic substrates, indicating its suitability for the development of targeted therapeutic agents.

Conclusion: These findings suggest the potential of these fungal proteases for developing novel anticoagulant therapies and diagnostic tools.

ABMMA-BMT is a modality that combines innovative complementary and alternative medicine techniques with low-voltage electrical energy, applying it to acupuncture points and meridians to bridge traditional Chinese medicine with modern bioelectric science. This involves the application of microcurrents (10-1000 μA) at acupoints to assess and correct for disrupted energy flow, as determined by electrical resistance measurements. Treatment involves the delivery of weak direct currents, which remove blockages in meridian channels, thereby promoting local blood circulation and tissue repair. Recent research suggests that pulsed electromagnetic fields (PEMFs) and microcurrent stimulation can influence neural signaling, gene expression, and redox balance, thereby benefiting conditions such as chronic pain, soft tissue injury, and functional dysregulation of the immune and endocrine systems. These results suggest that integrating bioelectric principles with traditional acupuncture concepts will support the hypothesis that ABMMA-BMT has the potential to regulate cellular processes and accelerate healing while avoiding invasive procedures. The mechanisms are still not well understood, but preliminary clinical data and experimental studies are good indicators of its therapeutic effect. Future research is needed to standardize treatment parameters and to clinically verify the efficacy of this modality, so that it can be incorporated as a conventional component of healthcare practice.

Introduction: Primary Sjögren's Syndrome (pSS) is a chronic autoimmune condition affecting lacrimal and salivary glands. While previous studies suggest potential associations between dyslipidemia and autoimmune diseases, the causal relationship between lipid-lowering medications and pSS remains unclear.

Methods: This study employed drug-targeted Mendelian randomization (MR) analysis to assess the impact of lipid-lowering drugs on pSS risk, focusing on genetic targets including HMGCR, PCSK9, NPC1L1, APOB, CETP, and LDLR. Data were sourced from the Global Lipids Genetics Consortium and UK Biobank. Significant single-nucleotide polymorphisms linked to LDL cholesterol were utilized as instrumental variables. Causal effects were estimated using Inverse Variance Weighted, Weighted Median, MR Egger, Simple Mode, and Weighted Mode methods. Robustness was ensured through heterogeneity and sensitivity analyses.

Results: The inhibition of HMGCR and CETP genes was found to be significantly associated with an increased risk of developing pSS (HMGCR: OR = 3.602, 95% CI [1.051, 12.344], p = 0.041; CETP: OR = 12.251, 95% CI [2.599, 57.743], p = 0.002).

Discussion: HMGCR and CETP may affect pSS risk via non-lipid pathways, suggesting distinct mechanisms among different lipid-lowering drug targets.

Conclusion: This study provides compelling evidence suggesting that lipid-lowering drugs may contribute to the risk of pSS, thus offering new insights for clinical intervention strategies.

In the pursuit of innovative vaccine delivery methods, this review explores the potential of spray drying for formulating inhalable vaccines. Traditional vaccine approaches face challenges in administration, storage, and accessibility, especially in resource-limited settings. Inhalable vaccines, utilizing techniques like spray drying, offer a promising solution. By bypassing systemic circulation and directly targeting the respiratory mucosa, inhalable vaccines can induce robust mucosal and systemic immune responses. Spray drying, a versatile technique, is particularly well-suited for formulating inhalable vaccines. It transforms liquid vaccine formulations into finely dispersed powders, enabling efficient delivery to the lungs. This review delves into the unique characteristics of spray-dried particles, their impact on immune system activation, and their role in overcoming traditional vaccine limitations. The exploration emphasizes the potential for spray drying to revolutionize vaccine development, providing a comprehensive overview of its applications and contributions to improving global public health.

Cervical cancer continues to be a critical public health concern globally, with increasing mortality rates, particularly in Low- and Middle-Income Countries (LMICs) where healthcare resources remain limited. With more than 300,000 fatalities each year, it is the fourth most frequent cancer in women globally. Long-term infection with carcinogenic Human Papillomavirus (HPV) variants, which cause cancer through viral proteins including E5, E6, and E7, is the leading cause of cervical cancer. These proteins interfere with host cellular functions, which promote the development and spread of cancer. Conventional treatment strategies, including chemotherapeutics and immunotherapies, have achieved varying degrees of success. However, protein-based therapeutics have recently emerged as a promising class of agents in oncology due to their ability to modulate specific molecular targets with high precision and specificity. These biologics interact with cell surface receptors and orchestrate essential signalling cascades, such as the NF-κB, MAPK, and PI3K/AKT pathways. Notably, new classes of protein therapeutics, such as toxin-based agents and Bromodomain and Extra-Terminal (BET) domain inhibitors, have shown effectiveness in disrupting tumor-promoting pathways. In addition to their direct antitumor activities, protein therapeutics also modify the tumor microenvironment, affecting stromal elements and lymphatic architecture, and ultimately promoting apoptosis. This review critically examines the landscape of protein-based therapeutic approaches for cervical cancer, delineating their mechanisms of action and highlighting their role in targeting inflammatory pathways-such as inflammasomes and cytokine networks-that contribute to tumor progression and immune modulation.

Introduction: Nanoparticles used in enzyme immobilization offer a high surface area- to-volume ratio, high chemical and thermal stability, and resistance to microbial attack.

Methods: The present investigation demonstrates the immobilization of Aspergillus oryzae β- galactosidase on silica nanoparticles via covalent binding. A greater yield of enzyme immobilization (89%) was attained on the developed nanobiocatalyst.

Results: It was observed that the immobilized and soluble enzymes had optimal pH and temperature values of 50 °C and 4.5, respectively. It was monitored that at pH 4.0, soluble β- galactosidase (SβG) exhibited 59% activity. However, the immobilized enzyme showed 92% activity under identical conditions. Similarly, 41% enzyme activity was retained at 70 oC by the free enzyme. Conversely, immobilized β-galactosidase (IβG) retained 70% activity under similar experimental conditions. Additionally, it was observed that at 5% galactose concentration, IβG showed 55% activity under one hour of incubation. However, under comparable experimental conditions, SβG showed 24% activity.

Discussion: It was observed that the immobilized enzyme was reusable, maintaining 90% of its activity even after five uses. The soluble enzyme demonstrated 62% and 70% lactose hydrolysis under the same conditions after 8 hours, while IβG demonstrated 74% and 85% lactose hydrolysis at 40°C and 50°C, respectively, in a controlled batch reactor experiment that was run for 10 hours.

Conclusion: Hence, owing to the greater reusability (90% after 5th repeated use) and excellent conversion of lactose at higher temperatures, the developed nanosupport may be used to produce lactose-free dairy products in continuous reactors on a large scale in biotechnology industries.

DNA hydrogels possess numerous unique and attractive features, including excellent biocompatibility and biodegradability, as well as inherent programmability, catalytic functionality, therapeutic potential, and precise molecular recognition and bonding capabilities. Furthermore, intelligent DNA hydrogels exhibit stimuli-responsive behaviors, transitioning between gel and sol states in response to various stimuli, including pH, temperature, enzymes, and others. Through intelligent, rational design and controlled preparation of DNA nanostructures, a broad spectrum of advanced applications has been realized. In this minireview, we focus on recent developments in the construction strategies, molecular structures, and functional mechanisms of DNA hydrogels. Additionally, representative applications of stimuli-responsive DNA hydrogels are discussed. Finally, challenges and the future outlook of DNA hydrogels are proposed.

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.