Zhongguo ying yong sheng li xue za zhi = Zhongguo yingyong shenglixue zazhi = Chinese journal of applied physiology最新文献

Rigosertib (ON 01910.Na) is a novel multi-kinase inhibitor initially developed as a non-ATP competitive agent, targeting dysregulated signalling pathways in cancer cells, notably RAS/RAF/MEK/ERK and PI3K/AKT, alongside Polo-like kinase 1 (PLK1). Preclinical studies have demonstrated its potent anticancer effects across various malignancies, including myelodysplastic syndromes (MDS), acute myeloid leukaemia (AML), and solid tumours such as pancreatic, colorectal, and breast cancers, by inducing apoptosis, mitotic arrest, and oxidative stress. Its selective cytotoxicity spares normal cells, making it a promising therapeutic candidate. However, clinical trials have yielded mixed results; while early-phase studies showed promise, particularly in hematologic cancers, phase III trials, such as those in MDS and pancreatic cancer, failed to demonstrate significant survival benefits over standard treatments. Challenges include variable patient responses, potential resistance mechanisms, and manageable but notable toxicities like myelosuppression and fatigue. Emerging evidence suggests rigosertib's potential in paediatric cancers like neuroblastoma and its synergy with therapies such as MEK inhibitors and hypomethylating agents. Future research should focus on optimizing combination strategies, identifying predictive biomarkers, and improving drug delivery to enhance its clinical efficacy and applicability across diverse cancer types.

Traditional Chinese medicine (TCM) bioactives display wide pharmacological effects, yet bulk transcriptomic studies mask their cell-specific actions. This study applied single-cell RNA sequencing to delineate immune, neural and hepatic responses to chemically characterized TCM constituents. Murine splenic, hippocampal and hepatic tissues were dissociated into single-cell suspensions, processed on a 10× Genomics platform, sequenced at high depth and analyzed with Seurat for clustering, marker annotation, differential expression and pathway enrichment; ligand-receptor interactions were inferred by CellChat, with RT-qPCR and immunofluorescence validation. From over 42,000 high-quality cells, we resolved 15 immune, 12 neural and 10 hepatic subtypes. TCM exposure induced NF-κB modulators in macrophages, neurotrophic gene expression in astrocytes and xenobiotic-metabolism programs in hepatocytes, while pathway analysis highlighted coordinated immune-hepatic detoxification and neuroprotective signaling. Ligand-receptor mapping revealed strengthened IL-10-STAT3 and hepatocyte-Kupffer cross-talk. These findings demonstrate that single-cell transcriptomics exposes previously hidden, cell-type-specific pharmacodynamics of TCM bioactives, laying a mechanistic foundation for precision-oriented herbal pharmacology and rational drug development.

The production procedures for pharmaceuticals and medical equipment have advanced significantly in recent years, especially considering the current pandemic and supply chain disruptions. Actually, 3D printers are a cutting-edge technology that enables its fabrication, such as custom-fit materials, equipment, and body parts, as well as meeting private patient requirements for certain conferences. As it gives a novel idea for delivery systems and technologies, 3DP is a sophisticated tool for creating straightforward, precise, affordable, organized, and customized DDSs. Recent examples of 3DP in the pharmaceutical industry include MNs, personalized ear treatment implants, oral dosage forms, contact lenses, drug-eluting implants for cancer purposes, and customized medical equipment (such cardiac implants and catheters).Using online computer-aided design (CAD) software to create a 3D model is the first step in 3DP. A 3D object is subsequently generated utilizing layer-by-layer (LBL) printing and a range of free software tools that can be found online. These techniques make the ongoing demand of manufacturing system potential. The 3D printing technology which is also referred as additive manufacturing, has adapted and transformed into a revolutionary tool in the field of pharmaceutical sciences, by providing earlier hidden potential for device development, personalized treatment and formulation of medication. This article covers how 3D printing technology can be used in pharmaceutical utility, focusing on how technology could modify dosage forms, drug delivery systems, and the ability to modify medications as per the need of an individual patients. The technology is discussed, along with different techniques such as fluid deposition modelling, binder jetting, stereolithography, selective laser sintering. The challenges faced while manufacturing are also discussed below. The article also highlights the emerging role of 3D printing in improving therapeutic outcomes, optimizing drug release profiles, and facilitating cost-effective manufacturing of personalized treatments.

This review looks at the pharmacokinetics, safety, and effectiveness of taletrectinib, a novel inhibitor that targets both ROS1 and NTRK, in patients with solid tumors and ROS1-positive non-small cell lung cancer (NSCLC). Objective response rates (ORR), progression-free survival (PFS), intracranial efficacy, and safety profiles are evaluated in the Review using phase I and phase II clinical trials, including both domestic and foreign research projects. Findings show that taletrectinib has a promising anticancer impact, good CNS penetration, and a solid safety record, especially in patients with brain metastases. These results imply that ROS1-positive cancers may benefit from taletrectinib as a treatment.

In the context of dysbiosis, chronic inflammation, and carcinogenesis, non-Helicobacter pylori bacteria are becoming more widely acknowledged as significant contributors to stomach diseases. The stomach contains a variety of bacterial communities, including Fusobacterium nucleatum, Streptococcus species, Lactobacillus species, Prevotella species, Veillonella species, and Propionibacterium acnes, according to studies employing next-generation sequencing. Because of adaptation processes like urease activity, acid-tolerant metabolism, and biofilm development, these organisms can survive in acidic environments. While some, like Lactobacillus, can create metabolites like lactic acid that may impact carcinogenic nitrosation reactions, others, including F. nucleatum and Streptococcus, cause inflammation through immune activation and cytokine production. A known stomach carcinogen, N-nitroso compound, may be formed more frequently if nitrate-reducing bacteria proliferate. Following H. pylori eradication, dysbiosis frequently involves elevated abundance of these taxa, which may impact stomach cancer risk and mucosal integrity. The need for more comprehensive microbiome-targeted therapeutic approaches is highlighted by mounting evidence that non-H. pylori bacteria interact either antagonistically or synergistically with H. pylori and host factors, causing intestinal metaplasia, gastritis, and tumour progression, even though causality is still being investigated.

Aim: To assess the theranostic potential of titanium nanoparticles (TiNPs), especially titanium dioxide nanoclusters, by assessing their distinct physicochemical characteristics and uses in biomedical domains as gene transport, immunotherapy, antimicrobial therapy, cancer, and biosensing.

Methods: The multifunctional properties of TiNPs were reviewed, with particular attention paid to their wide surface area, photo-reactivity, biocompatibility, and simplicity of surface modification. They were evaluated for use in drug delivery, photothermal and photodynamic therapy, biosensing, immunotherapy, gene therapy, antibacterial and antiviral activity, imaging (MRI, CT, fluorescence, optical, and photoacoustic imaging), and immunotherapy.

Result and discussion: TiNPs have been demonstrated to improve imaging accuracy and sensitivity while facilitating real-time therapy monitoring. Through targeted administration, they decreased systemic toxicity and increased therapeutic efficacy in oncology. Their production of reactive oxygen species (ROS) promotes their antiviral, antibacterial, and biofilm-inhibitory properties. TiNPs also make it easier to distribute checkpoint inhibitors for immunotherapy and to deliver genes through targeted uptake and electrostatic interactions. They also have high-resolution molecular imaging capabilities and perform better in biosensing and diagnostics.

Conclusion: By integrating therapeutic and diagnostic properties on one platform, titanium-based nanostructures demonstrate notable theranostic potential. The development of next-generation targeted medicines and diagnostics, better treatment results, and customized therapies are all made possible by their multifunctional nature.

The RP-HPLC methodology was used to establish a straightforward, accurate, and precise method for estimating Lanadelumab. The following chromatographic conditions were used: 5. Mobile phase: 0.1% OPA buffer: Acetonitrile in a ratio of 65:35; 5. Stationary phase: Agilent C18 250 x 4.6 mm; 5. Detection wavelength: 228.0 nm; column temperature: 30 °C; diluent: 50:50 acetonitrile: water; retention time: 2.280 min. As the most efficient approach, conditions were finalized. The standard was injected six times to study the system appropriateness characteristics, and the results fell well within the acceptable range. An analysis of linearity was conducted at 25% to 150% levels, and the R2 score was 0.999. Standard precision was determined to be 0.8, whereas repeatable precision was found to be 0.5. 0.08µg/ml is the LOD, while 0.24µg/ml is the LOQ. The assay of the marketed formulation was conducted using the described method, and 100.14% was found.

Hemocyanin is dissolved freely in hemolymph, the invertebrate blood substitute, in contrast to haemoglobin, which is encased in red blood cells. When oxygenated, this pigment gives mollusc and arthropod blood its characteristic blue or purple hue. This review article delves into the fascinating biology of hemocyanin, the copper-based oxygen-carrying protein responsible for "purple blood" in many invertebrates, contrasting its characteristics with the more familiar iron-based hemoglobin. The review used a variety of sources from 2020 to 2025, including preprint sites (bioRxiv, medRxiv), grey literature/press-release outlets including EurekAlert! and ScienceDaily, PubMed, Embase, Scopus, Web of Science, BIOSIS, and Google Scholar. While hemocyanin's unique properties allow for adaptation to diverse environments, its direct application as an artificial human blood substitute faces significant biological and immunological hurdles. The report then transitions to a comprehensive overview of recent advancements in artificial human blood transfusion, focusing on hemoglobin-based oxygen carriers (HBOCs), perfluorocarbon-based oxygen carriers (PFCs), and stem cell-derived red blood cells. This analysis critically examines their development, clinical trial outcomes, and the persistent challenges in achieving safe, effective, and widely available blood alternatives, highlighting the distinct roles and limitations of hemocyanin-derived products primarily in immunomodulation rather than oxygen transport.

Poorly soluble small compounds pose challenges in drug formulation due to low solubility, bioavailability, and therapeutic efficacy. These compounds often struggle to effectively target the disease due to their limited solubility. A large particle size further complicates reaching the desired site of action in the body. Reducing particle size through micronization or nanonization can enhance the efficacy of these active substances. Various methods, such as precipitation, milling, and high-pressure homogenization, are used to create nanocrystals, which can be delivered via multiple routes, with oral administration being preferred for safety and patient compliance. Nanonization is a key process in improving bioavailability, transforming micronized particles into nanoparticles under 1000 nm.

Pharmaceutical cocrystals have emerged as a transformative approach in drug development, enhancing the physicochemical properties of active pharmaceutical ingredients (APIs) such as solubility, bioavailability, stability, and dissolution rate without altering their pharmacological characteristics. Defined as multicomponent crystalline solids composed of two or more neutral molecules in a stoichiometric ratio, cocrystals are formed through non-ionic interactions like hydrogen bonding and π-π stacking. This review explores the evolution, design, preparation, and applications of pharmaceutical cocrystals, highlighting their ability to improve drug performance, enable controlled release, and offer intellectual property opportunities. Various preparation methods, including solvent-based (e.g., solvent evaporation, cooling crystallization) and solid-based (e.g., grinding, liquid-assisted grinding) techniques, are discussed alongside design approaches like hydrogen bonding propensity and the supramolecular synthonic approach. The review also addresses challenges such as molecular compatibility, thermodynamic barriers, and regulatory considerations. With regulatory acceptance from agencies like the FDA and ongoing advancements in crystal engineering, pharmaceutical cocrystals hold significant promise for optimizing drug delivery and formulation, necessitating further research to fully realize their potential in commercial applications.