Etanercept is a tumor necrosis factor inhibitor used widely for rheumatoid arthritis. Because patients respond differently, clinicians have increasingly explored whether measuring drug levels and antidrug antibodies could help guide treatment. This review brings together what is currently known about etanercept immunogenicity, serum concentrations, and the role of therapeutic drug monitoring, with a particular focus on practice in resource-limited settings such as Iraq. Major databases were searched (January 2010-June 2025) for clinical trials, observational studies, and systematic reviews of adults with rheumatoid arthritis receiving originator or biosimilar etanercept that reported antidrug antibodies, serum levels, or outcomes related to monitoring. Across randomized and real-world studies, etanercept generally showed low immunogenicity, with reported antidrug antibodies mostly below 15% and neutralizing antibodies rarely detected. Serum levels varied considerably between patients, and no robust therapeutic range could be defined. In most studies, etanercept concentrations did not consistently predict clinical response, and originator and biosimilar products appeared similar in terms of effectiveness and safety. Overall, these findings suggest that immunogenicity is not a major reason for etanercept treatment failure and that routine therapeutic drug monitoring is unlikely to help most patients. However, the evidence is heterogeneous, and real-world data from low- and middleincome countries, including Iraq, are still limited. Current evidence supports etanercept and its biosimilars as low-immunogenic options for rheumatoid arthritis, where routine monitoring is usually unnecessary. A more practical strategy may be to reserve targeted testing for selected non-responders while strengthening pharmacovigilance and local real-world research.
Targeted cancer therapies can enhance in vivo efficacy and decrease side effects by changing the distribution and exposure of specific biomolecules in tissues. Nevertheless, there are many cancer target proteins that cannot be targeted by traditional drugs. Some new technologies and drug design strategies have been applied to overcome these "undruggable" targets, among which the most well-known and classic technology is proteolysis-targeting chimeras (PROTACs). In order to design a better PROTAC structure for targeting "undruggable" targets, we elaborated in detail on the design of protein of interest (POI) ligands, E3 ligase ligands and linkers in PROTAC structures, the predicting of PROTAC ternary complex structures, and the advantages and disadvantages of using carriers in PROTAC delivery systems. In addition, this article also reviews the current research status of PROTAC targeting "undruggable" targets, such as kirsten rat sarcoma (KRAS), epidermal growth factor receptor (EGFR), c-Myc and p53. The challenges faced by PROTACs and the possible solutions were discussed, and the possibility of PROTAC broadening the range of drug therapeutic targets, especially the "undruggable" target, was prospected.
Current guidelines often recommend limiting benzodiazepine (BZD) use to 2-4 weeks. However, long-term use remains common, in part due to the challenges of tapering BZDs in the context of physical dependence and withdrawal risk. This publication aims to evaluate the current evidence on BZD tapering and outline key research recommendations. In the process of developing the Joint Clinical Practice Guideline on Benzodiazepine Tapering, which included a systematic review (SR), we identified important research gaps in the literature on BZD tapering. We used the guideline development process, SR, other overlapping reviews, and feedback collected during guideline development to inform proposed research recommendations. Our review identified wide variability in tapering strategies and outcome measures, significant methodological limitations, and a lack of safety and patient-reported outcomes in the literature. Based on this knowledge, we propose research recommendations to address key gaps in the existing evidence base, including (1) comparative effectiveness and pragmatic trials; (2) adjunctive interventions; (3) adaptive approaches; (4) use of very long-acting agents for tapering; and (5) shared decision-making strategies. We also highlight 5 methodological recommendations, including the importance of collecting standardized data on patient-centered outcomes, safety, BZD use history, at-risk populations, and the use of consistent terminology. There is a critical need for rigorous, standardized, and patient-centered research on BZD tapering. Addressing the identified research gaps will improve the quality of evidence supporting clinical decision-making, thereby enhancing the safety and effectiveness of tapering strategies for diverse patient populations.
Influenza A, an acute or subacute respiratory infectious disease caused by the influenza A virus (IAV), affects humans and animals, and poses a serious threat to public health. Currently, IAV prevention and treatment rely primarily on antiviral drugs and nebulization therapy. Although these methods offer rapid efficacy, prolonged or excessive use often induces drug resistance and sequelae, and has high costs. Throughout China's history, traditional Chinese medicine (TCM) has repeatedly resisted major epidemics, and substantially contributed to the survival and cultural continuity of the Chinese nation. Modern medical research has demonstrated that certain traditional Chinese medicinal formulas or their primary active constituents exhibit significant antiviral activity and immunomodulatory effects. Consequently, exploring the antiviral mechanisms of TCM or their active components, alongside their synergistic application with influenza vaccines and existing antiviral drugs, could enable novel approaches and research directions to achieve influenza prevention and control. This article reviews the current status of IAV transmission, as well as progress in modern medical research in influenza A prevention and treatment with TCMs or their active constituents.
The adverse events (AEs) associated with immune checkpoint inhibitors (ICIs) and antibody-drug conjugates (ADCs) are clinically significant. The early recognition and effective management of AEs are critical for improving prognosis and ensuring compliance. However, due to limitations in current AE management, the expert consensus and guidelines for the early prevention, diagnosis, and treatment of drug-associated pneumonitis remain insufficient. With the potentially increasing use of combined immunotherapy and ADCs, closer scrutiny of the overlapping and distinct AEs associated with these therapies is necessary. Focusing on checkpoint inhibitor-associated pneumonitis (CIP) and ADC-associated pneumonitis, this narrative review discusses the similarities and differences between these two conditions in terms of epidemiological characteristics, pathogenesis, clinical manifestations, and management to inform clinical practice and future research. The PubMed and China National Knowledge Infrastructure databases were searched to retrieve literature (including reviews, case reports, and clinical studies, expert consensuses, and clinical guidelines) on CIP and ADC-associated pneumonitis published in the past 7 years on September 1, 2025. Findings from multiple research articles were reviewed to generate a coherent summary of the progress in this field. Their epidemiological characteristics, pathogenesis, clinical manifestations, and management were compared to inform clinical practice. The latest research on CIP and ADC-associated pneumonitis is summarized. The management strategies for the two conditions differ significantly: CIP is diagnosed via clinical, imaging, and pathological findings, and is primarily treated with immunosuppressants (e.g., glucocorticoids); while ADC-associated pneumonitis relies on early detection via biomarkers, and its primary therapeutic strategy is the immediate discontinuation of ADC, followed by stepwise interventions with glucocorticoids, immunoglobulins, or cytokine antagonists based on the severity of the condition to reduce lung injury. Tailored treatment plans should be formulated based on the specific features of CIP or ADC-associated pneumonitis and individual patient factors. CIP and ADC-associated pneumonitis exhibit both differences and shared characteristics in epidemiology, pathogenesis, clinical presentation, diagnosis, and treatment. In clinical practice, it is essential to clarify the differences between the two approaches to explore the application of precision medicine in a clinically-oriented manner, and further refine intervention and prediction methods.
Atherosclerosis is the primary pathological foundation of various cardiovascular and cerebrovascular diseases. Although existing treatment strategies exhibit certain efficacy, they still encounter limitations such as pronounced side effects and a single-target approach. The oceans have nurtured a rich diversity of organisms, and the secondary metabolites they generate possess novel structures, diverse activities, and unique mechanisms of action, offering new prospects for the development of anti-atherosclerotic drugs. This paper reviews advancements related to research on marine-derived active substances that possess anti-atherosclerotic activity, as well as current challenges in research on active substances, with the objective of laying a foundation for the development of anti-atherosclerotic drugs.
Sarcopenia is an age-related syndrome characterized by the progressive loss of skeletal muscle mass, strength, and function, significantly impairing older adults' independence and quality of life. Given their anti-inflammatory, antioxidant, and metabolic regulatory properties, n-3 polyunsaturated fatty acids (n-3 PUFAs) have emerged as a promising nutritional strategy to mitigate this muscle degeneration. This review systematically synthesizes existing evidence regarding the association between n-3 PUFAs and sarcopenia. To capture the relevant literature, we searched PubMed, Web of Science, CNKI, and Wanfang Data using a combination of subject headings and free-text terms. We supplemented primary search terms-such as "n-3 polyunsaturated fatty acids," "omega-3 fatty acids," "sarcopenia," and "muscle mass"-with mechanism-related keywords like "inflammation," "muscle satellite cells," and "oxidative stress." We also manually screened the reference lists of the included literature. Our inclusion criteria encompassed interventional studies, observational studies, and high-quality reviews, while excluding conference abstracts, duplicate publications, and studies with incomplete data. This review first outlines the established biological mechanisms linking n-3 PUFAs to the pathological progression of sarcopenia, specifically detailing how these fatty acids improve muscle satellite cell function, suppress inflammation and oxidative stress, and ameliorate metabolic disorders. Next, we critically evaluate recent clinical studies and reviews, analyzing sources of study heterogeneity such as variations in sample size, intervention dose and duration, outcome measures, and baseline participant characteristics. We also highlight current research hotspots-including specialized pro-resolving mediators (SPMs), the gut-organ axis, combined interventions, and precision nutrition strategies-while emphasizing the functional differences between EPA and DHA to guide future intervention designs. Current evidence indicates that while n-3 PUFA supplementation can improve muscle strength and physical performance in older adults, its effects on muscle mass remain inconsistent. Addressing key research gaps, particularly the lack of standardized core outcome measures and unclear dose-response relationships, is critical. Ultimately, future research must prioritize developing high-bioavailability formulations, conducting personalized trials based on baseline n-3 PUFA status, and deepening investigations into inter-organ networks to translate these nutritional insights into effective sarcopenia prevention and management strategies.
Hypertrophic scars (HS) represent a significant clinical challenge due to their complex pathophysiology and resistance to conventional therapies, often resulting in persistent symptoms such as itching, pain, and impaired joint mobility that compromise patients' quality of life. Current treatment modalities, including compression therapy, pharmacological agents, radiation, silicone gel, and laser therapies, have faced limitations primarily due to inadequate drug penetration into the dense fibrotic scar tissue. In this context, microneedle-mediated controlled delivery systems have emerged as a promising pharmaceutical platform to enhance localized and sustained delivery of therapeutic agents, including small-molecule drugs, biologic proteins, small interfering RNA, and living cells, directly into HS. This article critically reviews the biological and formulation-related challenges associated with transdermal delivery in scar tissue and highlights recent innovations in microneedle design, material selection, and drug-loading techniques tailored for controlled release applications. Furthermore, it discusses the integration of proteins and cell-based therapies within microneedle platforms and their potential to modulate scar remodeling and inflammation. By addressing current limitations and exploring cutting-edge technologies, this review article aims to guide the development of effective microneedle-mediated strategies for pharmaceutical intervention in hypertrophic scar management.
An adverse drug reaction (ADR) is a harmful, unwanted patient response to a drug that happens at doses normally used for prevention, diagnosis, or treatment. Despite limited and inconsistent primary evidence on the cost of ADRs in Africa, this systematic review aims to synthesize the magnitude of ADR-related costs and assess the reporting quality of existing studies. The authors followed the Preferred Reporting Items for Systematic Reviews and Meta-Analyses checklist. Three databases (PubMed, Scopus, and ScienceDirect) and a hand search were employed. All empirical African cost-of-illness studies on ADRs were included regardless of publication year, disease type, or population, while letters to the editor, case reports, conference proceedings, and abstracts were excluded. Two independent authors conducted screening, data extraction, and quality assessment. A consensus-based cost-of-illness checklist was used to assess reporting quality. The primary outcome was the cost of adverse drug reactions, reported in 2024 international dollars (I$); the secondary outcome was the reporting quality of studies. A total of 324 studies were identified, of which eight were included in the final analysis. Nearly all studies reported only direct medical costs, excluding direct non-medical and indirect costs. ADR-related hospitalization costs per patient ranged from I$54.75 in Nigeria to I$7438.47 in South Africa. Costs were mainly driven by hospitalization, medications, and investigations, and influenced by patient, disease, and health system-related factors. While all studies described their population, objectives, time horizon, and data collection methods, many failed to report important methodological details. Adverse drug reactions impose a substantial economic burden through direct medical costs influenced by multiple factors; however, many studies lacked key reported details. Future research should adopt recommended methodologies and comprehensive cost reporting to improve the reliability of cost estimates.
Disease-modifying anti-rheumatic drugs (DMARDs) are the cornerstone of pharmacologic treatment for inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis and axial spondyloarthritis). DMARDs are immunomodulatory drugs which may increase the risk of infection, including surgical site infections; thus, some surgery guidelines recommend continuing some DMARDs and withholding others prior to surgery. On the other hand, discontinuation may result in worsening of the symptoms of the underlying inflammatory arthritis. Little is known about the optimal use of DMARDs during elective surgery. To assess the benefits and harms of perioperative interruption versus continuation of conventional synthetic (csDMARDs), biologic (bDMARDs) and targeted synthetic disease-modifying anti-rheumatic drugs (tsDMARDs) in people with inflammatory arthritis. We searched the Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE, Embase and two trial registers up to 24 March 2025. We included randomised controlled trials (RCTs) comparing temporary discontinuation or a dose reduction of DMARDs with continued medication perioperatively in adults with inflammatory arthritis (rheumatoid arthritis, psoriatic arthritis or axial spondyloarthritis) undergoing surgery (major orthopaedic surgery (including but not limited to joint arthroplasty and spinal fusion, or other)). When no RCTs were available for one or more types of DMARDs, we included observational studies, data from registries and insurance databases. The critical outcomes were flare of the underlying inflammatory disease, postoperative infections, prosthetic joint infections, mean disease activity score, function, total adverse events and serious adverse events. The prespecified primary time point was up to and including four weeks. As no trial reported outcomes before six weeks, we extracted the shortest time point reported for each outcome. We assessed risk of bias using the Cochrane risk of bias 1.0 tool. Two review authors independently used Cochrane methods for management of included studies. The main comparison was continuation of any DMARD versus discontinuation in the perioperative period. We synthesised effect estimates using a random-effects meta-analysis model. Three trials (306 participants) met inclusion. All compared perioperative discontinuation with perioperative continuation of csDMARDs in adults with rheumatoid arthritis undergoing elective orthopaedic surgery. Participants were 56.2 years old on average, and 83% of participants were women. In two trials, the discontinuation group stopped csDMARDs (methotrexate) two weeks prior to surgery and continued two weeks after the surgery, and in one trial, the discontinuation group stopped csDMARDs (leflunomide) one week prior to surgery and continued one month after the surgery. All trials were at risk of selection, performance, detection and selective outcome reporting biases. We did not find any trials assessing the perioperative use of (any) DMARDs in adults with rheumatoid arthritis undergoing non-orthopaedic surgery or adults with psoriatic arthritis or axial spondyloarthritis undergoing any surgery. We also did not find any trials assessing the perioperative use of bDMARDs, or tsDMARDs in adults with rheumatoid arthritis undergoing orthopaedic surgery. We identified nine observational studies with b/tsDMARDs in orthopaedic and non-orthopaedic surgery; six included participants with rheumatoid arthritis and the other three included mixed inflammatory arthritis populations. Results from the observational studies are presented narratively. As no trial reported outcomes at the designated primary time point of up to four weeks, we report the earliest time point for flare and postoperative infections (which varied across studies) and last follow-up for adverse events, serious adverse events and revision surgery. Low-certainty evidence indicates perioperative discontinuation of csDMARDs may increase the risk of flare, may have little or no effect on the number of people with postoperative infections, and may have little or no effect on the number of people reporting total or serious adverse events compared with perioperative continuation of csDMARDs. Only one trial measured prosthetic joint infections and reported no prosthetic joint infections in either group (very low-certainty evidence). None of the trials reported disease activity scores or function scores at follow-up. At eight months follow-up, 38/104 (36%) participants reported a flare in the discontinuation group compared to 0/120 (0%) in the continuation group (RR 32.99, 95% confidence interval (CI) 4.54 to 239.53, 2 studies, 224 participants, I2 = 0%). At 12 months follow-up, 5/145 (3%) participants in the discontinuation group had postoperative infections compared to 5/161 (3%) in the continuation group (RR 1.00, 95% CI 0.31 to 3.19, 3 studies, 306 participants). For total adverse events, 29/145 (20%) participants in the discontinuation group reported any adverse events compared to 17/161 (10%) in the continuation group (RR 1.89, 95% CI 0.20 to 18.00, 3 studies, 306 participants, I2 = 60%) after eight to 12 months follow-up. For serious adverse events, 9/113 (7%) participants reported events in the discontinuation group compared to 6/129 (5%) participants in the continuation group (RR 1.41, 95% CI 0.50 to 3.93, 2 studies, 242 participants, I2 = 4%) after 12 months follow-up. Evidence from observational cohort studies largely concurred with the findings from RCTs, indicating an increased risk of flare if DMARDs are discontinued, with no apparent reduction in the risk of postoperative infection. While we could not estimate the risk of prosthetic joint infections from trial data, observational data suggests that perioperative discontinuation of DMARDs does not reduce the likelihood of this outcome occurring. Perioperative discontinuation of DMARDs may increase the risk of flare, and may have little or no effect on the number of people with postoperative infections, the number reporting adverse events and serious adverse events. None of the studies reported on mean disease activity or function. The evidence is limited to rheumatoid arthritis and csDMARDs. Observational studies largely support the findings that there may be a risk of flare with discontinuation of csDMARDs in people with other inflammatory arthritis, but the risks associated with perioperative discontinuation of biologic or targeted synthetic DMARDs are less clear. Editorial note: This is a living systematic review. We search for new evidence approximately yearly and update the review when we identify relevant new evidence. Please refer to the Cochrane Database of Systematic Reviews for the current status of this review. This Cochrane review had no dedicated funding. Protocol (2022). DOI: 10.1002/14651858.CD015096.
Superficial fungal infections, such as dermatophytosis, candidiasis, and pityriasis versicolor, are prevalent worldwide. They put a heavy burden on healthcare systems, mainly because infections often recur, linger for months, and do not always respond well to standard treatments. The conventional topical creams and ointments fail to achieve the goal of treatment as they are often unable to penetrate deeply, do not stay long enough on the site of application, and patients mostly stop using them before the completion of the course. This review explores the biology of superficial fungal infections, the limitations of existing topical treatments, and the advancement of nanotechnology-based carriers for the topical treatment of fungal diseases. From the recent literature, it was found that there has been noticeable progress in innovative drug delivery approaches. These novel systems are designed to improve drug solubility, drug permeation, and adherence and spreadability of the formulation on the site of application. Several nanocarrier systems, such as liposomes, niosomes, ethosomes, and solidlipid nanoparticles, have demonstrated improved therapeutic outcomes compared with older topical formulations. Novel drug delivery systems do not just improve the solubility and permeation of drugs but also reduce the frequency of doses, mitigate side effects, and help bypass mechanisms that commonly cause antifungal resistance. The review highlights the biology of fungal infections, as well as the safety, clinical use, limitations, and long-term potential of novel approaches. The study provides broad insights into innovative approaches that could significantly transform treatment strategies for superficial fungal infections in the future.
Nicotine, as the main bioactive component in tobacco, activates the nicotinic acetylcholine receptors (nAChRs) in the nervous system, triggering a series of complex neurobiological responses, thereby facilitating the formation and maintenance of rewarding effect behaviors. Current research has systematically revealed that the physiological effects of nicotine involve multiple nAChRs subtypes and their regulatory role on the central dopamine system, further influencing the function of neural circuits and behavioral manifestations. At the same time, the interaction between genetic factors and the environment plays an important role in the nicotine reward effect, and neuro-immune responses and dynamic changes in brain functional networks have also been gradually confirmed to be closely related to the formation mechanism of the reward effect. This article systematically reviews the molecular-level interactions between nAChRs and the nicotine ligand, and the molecular mechanism, genetic regulation, and neural circuit characteristics of the neurophysiological effects of nicotine, combined with the latest neuroimaging and genetic progress, focusing on analyzing the current nicotine consumption strategies (such as the transformation of nicotine usage methods) and the development trend of personalized treatment based on nicotine in the future. It also discussed the differences in physiological effects between nicotine and other tobacco alkaloids. This will help researchers to have a more systematic and in-depth understanding of nicotine and its biological characteristics, and help explore more scientific and efficient nicotine biological targets.
Acute myeloid leukemia (AML) can be transformed by the malignant transformation of hematopoietic progenitor cells at different stages of normal myeloid cell differentiation and development, thus leading to infection, anemia, bleeding symptoms. It is a common highly heterogeneous hematologic malignancy, the incidence of which is on the rise year by year. The treatment of AML includes chemotherapy, hematopoietic stem cell transplantation and targeted therapy, etc. However, due to the highly heterogeneous nature of AML and the easy recurrence, the treatment is difficult and the cure rate is low. In recent years, combination therapy based on venetoclax has become one of the important research directions for the treatment of AML, and its efficacy has gradually received the attention of clinical researchers. This paper reviews the mechanism of action of venetoclax and its application in the current treatment of AML. Through an in-depth discussion of venetoclax and its combination therapy AML related clinical trials, the emergence of resistance mechanisms to venetoclax and potential strategies to overcome its resistance are summarized. 以维奈克拉为基础的联合治疗在急性髓系白血病中 的研究进展. 急性髓系白血病（AML）可以由正常髓系细胞分化发育过程中不同阶段的造血祖细胞恶性变转化而来，从而导致感染、贫血、出血等症状，是一种常见的高度异质性血液系统恶性肿瘤，发病率呈逐年上升趋势。治疗AML的方法包括化疗、造血干细胞移植和靶向治疗等，但由于AML的高度异质性和易复发等特点，治疗难度较大，治愈率较低。近年来，以维奈克拉为基础的联合治疗成为治疗AML的重要研究方向之一，其疗效逐渐受到临床研究者的关注和重视。本文综述了维奈克拉的作用机制、在当前AML治疗中的应用，通过深入讨论维奈克拉及其联合治疗AML的相关临床试验，对维奈克拉耐药机制的出现和克服其耐药的潜在策略进行了归纳总结.
Deuterium, the heavy isotope of hydrogen, has unfolded as a cornerstone in modern drug discovery due to its potential to influence metabolic stability and pharmacokinetic behavior. The deuterium kinetic isotope effect (KIE), which strengthens carbon-deuterium bonds, make it possible to improve therapeutic efficacy while maintaining pharmacological activity. Although some deuterated drugs, notably donafenib and deutetrabenazine, have demonstrated clinically significant efficacy, their limited use is an effect of ongoing challenges with metabolic switching and species-specific variation, as well as inadequate mechanistic understanding. This review presents a systematic discussion of the recent innovations in site-selective deuteration, the principles that underpin the KIE process, and the effects of deuterium substitution on drug metabolism, toxicity, and blood-brain barrier penetration. It illustrates novel implications in oncology, rare diseases, and central nervous system disorders, as well as the integration of deuterated chemistry with modalities such as proteolysis-targeting chimaeras, peptides, and nucleic acid therapeutics. Furthermore, the review's discussion includes the current challenges, synthesis, analytical limits, and regulatory considerations that influence further development. Overall, the review offers a strategic roadmap for utilizing deuterium-enabled molecular engineering to accelerate the development of next-generation precision medicine, guiding rational design, innovation toward safer, longer-lasting, and more effective treatments.
This special issue commemorates the joint hosting of the 23rd International Congress of the International Society of Ethnopharmacology and the 2nd International Congress of the African Phytomedicine Scientific Society. The conference aimed to advance ethnopharmacology and phytomedicine through 13 multidisciplinary contributions. This collection of manuscripts explores phytochemistry, pharmacological evaluation, translational medicine, and clinical applications of medicinal plants and traditional knowledge systems. Studies investigated the anticancer potential of Açaí extracts, chemotaxonomic and therapeutic insights into Stachys species, and neuroprotective activities of Catha edulis, Datura stramonium, Mesembryanthemum tortuosum, and Polygala virgata in Parkinson's disease models. The anti-ageing effects of fermented Persicaria senegalensis, analgesic and antipyretic properties of Haplanthodes tentaculata, anticancer activity of Aframomum alboviolaceum, and aphrodisiac efficacy of Citropsis articulata are also explored. Broader perspectives included reviews and bibliometric analyses of ethnoveterinary medicine in Africa, as well as historical and regulatory evaluations of natural products in the Greek Pharmacopoeia. Collectively, these studies emphasize the importance of integrating traditional knowledge and current scientific methodologies, while promoting ethical collaboration, innovation, sustainability, and evidence-based development of phytomedicines. The issue further reinforces international partnerships aimed at strengthening African research capacity and advancing global health outcomes through ethnopharmacological research.
SUMMARYInfluenza viruses remain a serious global health problem, causing annual epidemics and potential pandemics with significant morbidity and mortality. Antiviral therapy, particularly with direct-acting antivirals (DAAs), is a critical component of influenza control. This comprehensive review analyzes the current landscape of DAA drugs, with special attention paid to the complexity of synthesis, pharmacokinetic properties, and the development of antiviral resistance. We evaluated approved treatments, including neuraminidase (NA) inhibitors, viral RNA polymerase inhibitors, hemagglutinin (HA) inhibitors, and M2 ion channel blockers. We identify several critical obstacles to effective treatment: (i) the high genetic variability of influenza viruses, which facilitates the emergence of resistance, particularly in the case of M2 blockers (widespread) and, to a lesser but concerning extent, NA and polymerase inhibitors, both through natural evolution and selective pressure during drug treatment, and (ii) the suboptimal pharmacokinetic profiles of many existing drugs. This review provides a crucial framework for evaluating existing and investigational drugs for influenza, emphasizing the need to develop balanced therapeutic strategies that consider efficacy, resistance management, and global accessibility. The novelty of this review is a comprehensive comparative analysis of not only the drugs officially recommended by the WHO but also a wide range of other anti-influenza drugs approved in individual countries or under development. We have identified key comparative aspects that are discussed in detail here and are not always brought together in other reviews. The purpose of the article is to provide a generalized overview of the current state of knowledge, identify key trends and problems, and discuss future prospects without providing new primary data or experimental results.
Multidrug resistance, inadequate tumor penetration, and systemic toxicity significantly limit the effectiveness of conventional chemotherapy in solid tumors. Scaffold-based localized chemotherapy offers a promising approach to overcome these challenges by delivering drugs directly to the tumor site with sustained and controlled release. This article reviews electrospun nanofiber scaffolds, injectable hydrogels, 3D-printed scaffolds, and composite biomaterial scaffolds engineered from biodegradable and bioresponsive polymers such as PLGA, PCL, chitosan, and hyaluronic acid. The influence of drug incorporation strategies, including surface loading, encapsulation, and post-fabrication soaking, on drug loading capacity, degradation behavior, mechanical strength, and release kinetics is examined. Preclinical studies in breast cancer, glioblastoma, colorectal cancer, and pancreatic cancer demonstrate that scaffold-based systems increase local drug concentration, reduce systemic toxicity, and improve therapeutic outcomes. Advanced systems such as dual-drug platforms, stimuliresponsive constructs, and immunomodulatory scaffolds show additional potential to modulate the tumor microenvironment, prevent recurrence, and enhance antitumor immune responses. Moreover, technologies such as electrospinning are well established, whereas advanced modalities like 4D bioprinting remain in early developmental stages, limiting their current translational readiness. The application of scaffolds in cancer therapy highlights their theranostic potential, combining controlled chemotherapeutic delivery with capabilities for tissue support, microenvironment modulation, and functional integration with biological systems. Nanostructured polymer scaffolds represent a promising strategy for localized chemotherapy in solid tumors. By overcoming key limitations of systemic drug delivery, these platforms enhance treatment precision, improve patient outcomes, and demonstrate strong translational potential for next-generation oncology therapeutics.
Lung cancer is the malignant tumor with the highest incidence and mortality rate worldwide. The current treatment methods have limited efficacy, and the prognosis of patients is poor. There is an urgent need to explore new therapeutic targets and strategies. Epigenetic modification disorders are closely related to the occurrence and development of tumors. Among them, histone deacetylase 1 (HDAC1), as a key epigenetic regulatory molecule, participates in the regulation of biological processes such as cell proliferation, differentiation, and apoptosis. HDAC1 is highly expressed in lung cancer, and its expression level is closely related to the malignancy degree, clinical stage, and poor prognosis of lung cancer. Abnormal activation of HDAC1 is also one of the core factors for the resistance of lung cancer to chemotherapy, targeted therapy, and immunotherapy. The development of HDAC1 inhibitors provides a new direction for the treatment of lung cancer, and the combination with chemotherapy, targeted therapy, and immunotherapy can significantly enhance the synergistic anti-tumor effect. This article systematically reviews the structural characteristics and physiological functions of HDAC1, deeply explores its regulatory mechanism in lung cancer, elaborates on its association with lung cancer resistance, and summarizes the research and development progress, clinical trial status, and challenges of HDAC1 inhibitors, with the aim of providing new ideas for the precise treatment of lung cancer.
. 【中文题目：HDAC1在肺癌中的潜在作用机制及研究进展】 【中文摘要：肺癌是全球发病率与死亡率最高的恶性肿瘤。当前治疗手段疗效有限，患者预后不佳，亟需探索新的治疗靶点与策略。表观遗传修饰失调与肿瘤发生发展密切相关，其中组蛋白去乙酰化酶1（histone deacetylase 1, HDAC1）作为关键的表观遗传调控分子，参与调控细胞增殖、分化、凋亡等生物学过程。HDAC1在肺癌中呈高表达，且其表达水平与肺癌恶性程度、临床分期及不良预后密切关联。HDAC1异常激活也是肺癌化疗、靶向治疗及免疫治疗耐药的核心因素之一。HDAC1抑制剂的研发为肺癌治疗提供了新方向，且与化疗、靶向治疗及免疫治疗联用能够显著增强协同抗肿瘤效果。本文系统综述了HDAC1的结构特征与生理功能，深入探讨其在肺癌中的调控机制，阐述其与肺癌耐药的关联，并总结HDAC1抑制剂的研发进展、临床试验现状及面临的挑战，以期为肺癌的精准治疗提供新思路。
】 【中文关键词：肺肿瘤；HDAC1；表观遗传修饰；HDAC1抑制剂】.
Neglected Tropical Diseases (NTDs) are debilitating conditions that predominantly affect impoverished populations. Lack of healthcare resources and education often results in these diseases being untreated or undiagnosed, leading to chronic health issues, lost productivity, and economic hardships. Individuals affected by NTDs face poor environmental sanitation, malnourishment, and the unavailability of an effective healthcare system, making treatment challenging. The associated stigma further isolates these individuals. There are challenges in the control, prevention, diagnosis and treatment of the various neglected protozoan diseases. Current pharmacological treatments are hampered by severe toxicity, prolonged regimens or parenteral administration, emerging resistance, inability to clear latent parasite forms, and unsuitability for resource-constrained settings. Additionally, there is a paucity of new studies on neglected tropical protozoan diseases due to limited global interest and, consequently, low investment. Our study discusses the challenges posed by conventional treatment options for protozoan NTDs. It also reviews recent studies investigating the use of various nanotechnology-based drug delivery systems, including lipid nanoparticles, polymer nanoparticles, metallic nanoparticles, carbon nanotubes, composites, and smart nanocarriers, for the treatment of neglected protozoan diseases, including leishmaniasis, Chagas disease, and trypanosomiasis. We also discuss the use of these nanocarriers in the prevention, control and diagnosis of protozoan NTDs. Nanotechnology has emerged as a promising strategy to overcome barriers militating against the effective management of protozoan NTDs.
Emodin, rhein, aloe-emodin, physcion, and chrysophanol are five representative anthraquinones (AQs) in rhubarb. They exhibit diverse pharmacological activities, including antitumor, anti-inflammatory, antibacterial, and antioxidant effects, and are widely used in traditional Chinese medicines (TCMs), dietary supplements, and functional foods. However, with their increasing application, the potential toxicity of AQs has become increasingly prominent. Moreover, their toxic mechanisms and metabolism-related toxicities remain incompletely elucidated, which has limited their clinical development and safe application to a certain extent. This paper systematically reviews the toxicological characteristics, toxic mechanisms, and metabolism-related toxicity of the five major AQs in rhubarb, and explores research strategies for AQs toxicity based on advanced technologies, aiming to provide new insights and references for their safe application and further studies. A comprehensive search was conducted in PubMed, Google Scholar, Web of Science, and CNKI for peer-reviewed research articles and reviews published in the past 15 years. The research progress of the five major rhubarb AQs and the applications of cutting-edge technologies in their toxicity studies were summarized. The toxicities of AQs mainly target the liver, kidney, heart, reproductive system, and nervous system. Their toxic mechanisms involve multiple pathways, including mitochondrial apoptosis, oxidative stress, death receptor pathway, endoplasmic reticulum (ER)-related apoptosis, caspase-dependent apoptosis, autophagy, inflammation, DNA damage, and bilirubin metabolism. The in vivo metabolism of AQs is complicated, and both Phase I and Phase II metabolites are linked to toxicity. The diverse metabolites can interconvert and undergo various reactions in vivo, posing great challenges for toxicity research. In the future, the application of advanced technologies, such as multi-omics and single-cell sequencing, artificial intelligence (AI) and computer simulation, microfluidics, and mass spectrometry imaging (MSI) will provide strong support for accurately elucidating toxic mechanisms, enabling toxicity prediction, and optimizing detoxification strategies, and will become effective approaches to advance toxicity studies of rhubarb AQs. The intrinsic toxicity and complex metabolic processes of rhubarb AQs restrict their clinical application. Current studies on the toxic mechanisms, metabolism-toxicity relationships, and multifactorial regulation of AQs still require further in-depth investigation. Future research should focus on the metabolism-toxicity relationship, key toxic targets, and detoxification strategies of AQs, and establish an integrated toxicity research system combined with advanced technologies, so as to provide robust support for the safe application and clinical development of rhubarb AQs.