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

Iridium therapy is changing how cancer is treated in the future. Because of their remarkable photophysics, redox sensitivity, and structural adaptability, Ir (III) complexes offer a powerful and multipurpose solution for precision oncology. These substances can be engineered to target particular Compounds organelles, photoinduced activation, and real-time imaging on a single molecular platform, which allows for simultaneous diagnosis and treatment, unlike conventional chemotherapeutics. This review highlights the recent surge in iridium complex synthesis and biomedical applications, with a focus on developments within the past five years. We address their many structural classes, including cyclometalated compounds, mononuclear Ir (III) species, and formulations based on nanoparticles, emphasizing their subcellular accumulation patterns, intracellular trafficking, and cellular uptake methods. Because iridium complexes are better at generating reactive oxygen species (ROS), causing mitochondrial damage, and fragmenting DNA, they can kill cancer cells selectively without harming healthy tissue. Novel strategies such as administration that responds to the tumor microenvironment, induction of immunogenic cell death, and combination with photothermal or radiation are propelling iridium medicines to the forefront of multimodal cancer treatment. Iridium complexes, which are distinguished by their improved pharmacokinetics and biodegradability due to clever nanocarrier engineering, have significantly lower systemic toxicity than platinum equivalents. Iridium-based platforms are powerful anticancer tools with strong translational potential that bridge biology and chemistry, imaging and therapy. This review is meant to serve as a last resort for medicinal chemists, scientists working in nanomedicine, and oncologists who want to maximize iridium's anti-cancer potential.

The discovery of ROS1 and NTRK gene fusions has transformed treatment strategies for a specific group of cancers, particularly non-small cell lung cancer (NSCLC). First-generation tyrosine kinase inhibitors (TKIs) such as crizotinib displayed significant early reactions but faced challenges due to restricted central nervous system (CNS) penetration and mutation resistance, while entrectinib and larotrectinib expanded treatment options but also experienced resistance. Taletrectinib (DS-6051b, AB-106) is an orally bioavailable, next-generation selective inhibitor of ROS1 and NTRK kinases, designed to tackle these issues. Preclinical assessments demonstrated its strong efficacy against both wild-type and resistant kinases, including the clinically challenging ROS1 G2032R mutation, alongside good CNS penetration and prolonged intracranial responses. Clinical studies, like the notable TRUST and TRUST-II trials, have demonstrated elevated objective response rates in TKI-naïve NSCLC patients (often exceeding 85-90%) and substantial effectiveness in groups pretreated with crizotinib. Basket trials are expanding their evaluation to include NTRK fusion-positive solid tumors, confirming a tumor-agnostic strategy. Safety data shows an acceptable toxicity profile, mainly featuring gastrointestinal and hepatic adverse effects, with fewer neurocognitive side effects compared to lorlatinib. Regardless of these advancements, challenges remain, including the possibility of new resistance mutations, limited patient enrollment in early-phase trials, and the critical need to enhance the management of long-term toxicities. Current trials and regulatory activities in China, the U.S., and other locations demonstrate taletrectinib's growing clinical significance. Taletrectinib's well-rounded pharmacological attributes of systemic action, intracranial effectiveness, resistance range, and tolerability render it an intriguing enhancement to the framework of precision oncology.

Introduction: Worldwide, heart failure remains one of the leading causes of death and morbidity. Drug-induced cardiotoxicity is a significant adverse effect on cardiovascular health and may arise from various pathogenic mechanisms. Several therapeutic agents have been associated with cardiac injury due to their interactions with cardiac receptors and pathways. Understanding these mechanisms is crucial for minimizing cardiovascular risks and improving patient safety.

Material and methods: This review systematically explores the diverse mechanisms of drug-induced cardiotoxicity by analyzing existing literature and clinical studies. It highlights the commonly implicated therapeutic agents, including lidocaine, trastuzumab, orciprenaline, azidothymidine, anthracyclines, fluoropyrimidines, NSAIDs, terodiline, digitalis, and antiviral drugs. The study also identifies major receptors involved in the pathogenic processes leading to cardiotoxicity. Furthermore, risk factors predisposing patients to cardiac damage and current strategies for early detection, monitoring, and prevention are critically reviewed to provide a comprehensive understanding of the topic.

Conclusion: A thorough understanding of drug-receptor interactions and cardiotoxic pathways is essential to reduce the incidence of drug-induced cardiac injury. Implementing multidisciplinary approaches can help minimize cardiovascular risks without compromising therapeutic efficacy. Continued research on cardioprotective interventions and early diagnostic strategies will enhance patient safety and ensure the long-term success of modern pharmacotherapy.

Background: Diabetic glaucoma is a serious eye disorder that can lead to permanent vision loss and is increasingly seen in individuals with long-term diabetes. With its rising global incidence, there is a critical need for early and reliable methods of detection to prevent severe complications.

Objective: This study highlights the growing role of artificial intelligence (AI), especially deep learning technologies, in identifying diabetic glaucoma at an early stage. It also reviews progress in bionic eye technologies designed to help restore vision in affected individuals.

Methods: Relevant scientific literature was reviewed by searching databases including PubMed, Taylor francis, ScienceDirect, MDPI, and Bentham. Articles published up to 2025 were considered, focusing on terms such as "diabetic glaucoma,""retinal imaging,""deep learning,""AI in eye care,""bionic eye,"and "neuroprosthetics."Studies were selected based on their relevance to diagnostic innovations and vision-restoration technologies.

Results: Recent developments in AI have enabled more accurate interpretation of retinal images, such as those from fundus cameras and optical coherence tomography (OCT), aiding in early detection of structural changes linked to glaucoma. At the same time, bionic eye systems-based on neuroprosthetic implants-are showing promise in partially restoring vision in cases of severe visual impairment.

Conclusion: Combining AI-powered diagnostics with emerging bionic eye technologies represents a major shift in managing diabetic glaucoma. These innovations have the potential to improve early detection and offer new options for visual rehabilitation, paving the way for more effective patient care in ophthalmology.

Resistant Hypertension is a significant clinical problem. It is found in the most of individuals who, even with the greatest multi-drug therapy, are not able to manage their blood pressure. A new dual endothelin receptor antagonist (ERA) called aprocitentan (Aprocitirom) inhibits both ETA and ETB receptors. It has emerged as a potentially useful treatment for such patients. This review article considers Aprocitentan's pharmacological profile, preclinical development, clinical efficacy, and potential. Preclinical experiments revealed that Aprocitentan possesses vasodilatory, anti-inflammatory, & anti-fibrotic activities. It is also well absorbed from the gastrointestinal tract and safe in various species. The Phase I trials reinforced that it is well tolerated and can be administered once daily. In Phase II trials, Aprocitentan induced dose-proportional reductions in systolic and diastolic blood pressure in patients with resistant hypertension. The critical Phase III PRECISION trial also validated its efficacy. It showed impressive and sustained decreases in blood pressure, with a favorable safety profile and low hepatotoxicity, and minimal fluid retention. An important step forward in the treatment of ERA has come with the FDA and EMA approval of aprocetentan in resistant hypertension. Its metabolism, which is not dependent on CYP enzymes, adds to its therapeutic applications and minimizes the likelihood of drug interactions. Subgroup analysis and further real-world studies indicate further benefits in patients with metabolic disorders and chronic kidney disease. Aprocitentan could potentially prove useful in the future for vascular disease, heart failure, and diabetic nephropathy. Clarifying its potential role in the future to treat hypertension and cardiorenal disease will only be discernible through longer-term trials on cardiovascular endpoints and cost-effectiveness.

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.