miR-135b: An emerging player in cardio-cerebrovascular diseases.

miR-135 is a highly conserved miRNA in mammals and includes miR-135a and miR-135b. Recent studies have shown that miR-135b is a key regulatory factor in cardio-cerebrovascular diseases. It is involved in regulating the pathological process of myocardial infarction, myocardial ischemia/reperfusion injury, cardiac hypertrophy, atrial fibrillation, diabetic cardiomyopathy, atherosclerosis, pulmonary hypertension, cerebral ischemia/reperfusion injury, Parkinson's disease, and Alzheimer's disease. Obviously, miR-135b is an emerging player in cardio-cerebrovascular diseases and is expected to be an important target for the treatment of cardio-cerebrovascular diseases. However, the crucial role of miR-135b in cardio-cerebrovascular diseases and its underlying mechanism of action has not been reviewed. Therefore, in this review, we aimed to comprehensively summarize the role of miR-135b and the signaling pathway mediated by miR-135b in cardio-cerebrovascular diseases. Drugs targeting miR-135b for the treatment of diseases and related patents, highlighting the importance of this target and its utility as a therapeutic target for cardio-cerebrovascular diseases, have been discussed.

CUTS RNA Biosensor for the Real-Time Detection of TDP-43 Loss-of-Function.

Given the mounting evidence implicating TDP-43 dysfunction in several neurodegenerative diseases, there is a pressing need to establish accessible tools to sense and quantify TDP-43 loss-of-function (LOF). These tools are crucial for assessing potential disease contributors and exploring therapeutic candidates in TDP-43 proteinopathies. Here, we develop a sensitive and accurate real-time sensor for TDP-43 LOF: the CUTS (CFTR UNC13A TDP-43 Loss-of-Function) system. This system combines previously reported cryptic exons regulated by TDP-43 with a reporter, enabling the tracking of TDP-43 LOF through live microscopy and RNA/protein-based assays. We demonstrate CUTS' effectiveness in detecting LOF caused by TDP-43 mislocalization and RNA binding dysfunction, and pathological aggregation. Our results highlight the sensitivity and accuracy of the CUTS system in detecting and quantifying TDP-43 LOF, opening avenues to explore unknown TDP-43 interactions that regulate its function. In addition, by replacing the fluorescent tag in the CUTS system with the coding sequence for TDP-43, we show significant recovery of its function under TDP-43 LOF conditions, highlighting CUTS' potential for self-regulating gene therapy applications. In summary, CUTS represents a versatile platform for evaluating TDP-43 LOF in real-time and advancing gene-replacement therapies in neurodegenerative diseases associated with TDP-43 dysfunction.

Advancing bone regeneration: Unveiling the potential of 3D cell models in the evaluation of bone regenerative materials.

Bone, a rigid yet regenerative tissue, has garnered extensive attention for its impressive healing abilities. Despite advancements in understanding bone repair and creating treatments for bone injuries, handling nonunions and large defects remains a major challenge in orthopedics. The rise of bone regenerative materials is transforming the approach to bone repair, offering innovative solutions for nonunions and significant defects, and thus reshaping orthopedic care. Evaluating these materials effectively is key to advancing bone tissue regeneration, especially in difficult healing scenarios, making it a critical research area. Traditional evaluation methods, including two-dimensional cell models and animal models, have limitations in predicting accurately. This has led to exploring alternative methods, like 3D cell models, which provide fresh perspectives for assessing bone materials' regenerative potential. This paper discusses various techniques for constructing 3D cell models, their pros and cons, and crucial factors to consider when using these models to evaluate bone regenerative materials. We also highlight the significance of 3D cell models in the in vitro assessments of these materials, discuss their current drawbacks and limitations, and suggest future research directions. STATEMENT OF SIGNIFICANCE: This work addresses the challenge of evaluating bone regenerative materials (BRMs) crucial for bone tissue engineering. It explores the emerging role of 3D cell models as superior alternatives to traditional methods for assessing these materials. By dissecting the construction, key factors of evaluating, advantages, limitations, and practical considerations of 3D cell models, the paper elucidates their significance in overcoming current evaluation method shortcomings. It highlights how these models offer a more physiologically relevant and ethically preferable platform for the precise assessment of BRMs. This contribution is particularly significant for "Acta Biomaterialia" readership, as it not only synthesizes current knowledge but also propels the discourse forward in the search for advanced solutions in bone tissue engineering and regeneration.

Targeting lymph nodes for enhanced cancer vaccination: From nanotechnology to tissue engineering.

Lymph nodes (LNs) occupy a critical position in initiating and augmenting immune responses, both spatially and functionally. In cancer immunotherapy, tumor-specific vaccines are blooming as a powerful tool to suppress the growth of existing tumors, as well as provide preventative efficacy against tumorigenesis. Delivering these vaccines more efficiently to LNs, where antigen-presenting cells (APCs) and T cells abundantly reside, is under extensive exploration. Formulating vaccines into nanomedicines, optimizing their physiochemical properties, and surface modification to specifically bind molecules expressed on LNs or APCs, are common routes and have brought encouraging outcomes. Alternatively, porous scaffolds can be engineered to attract APCs and provide an environment for them to mature, proliferate and migrate to LNs. A relatively new research direction is inducing the formation of LN-like organoids, which have shown positive relevance to tumor prognosis. Cutting-edge advances in these directions and discussions from a future perspective are given here, from which the up-to-date pattern of cancer vaccination will be drawn to hopefully provide basic guidance to future studies.

Neuroprotective effects of the salidroside derivative SHPL-49 via the BDNF/TrkB/Gap43 pathway in rats with cerebral ischemia.

Ischemic stroke is a common intravascular disease and one of the leading causes of death and disability. The salidroside derivative SHPL-49, which we previously synthesized, significantly attenuates cerebral ischemic injury in a rat model of permanent middle cerebral artery occlusion. To explore the neuroprotective mechanism of SHPL-49, the effects of SHPL-49 on the expression levels of neurotrophic factors in neurons and microglia and the polarization of microglia were investigated in the present study. SHPL-49 activated the brain-derived neurotrophic factor (BDNF) pathway, decreased the number of degenerated neurons, and accelerated neurogenesis in rats with cerebral ischemia. In addition, SHPL-49 promoted the polarization of microglia toward the M2 phenotype to alleviate neuroinflammation. In BV2 cells, SHPL-49 upregulated CD206 mRNA and protein levels and inhibited CD86 mRNA and protein levels. SHPL-49 also increased neurotrophic factor secretion in BV2 cells, which indirectly promoted the survival of primary neurons after oxygen-glucose deprivation (OGD). Proteomics analysis revealed that SHPL-49 promoted growth-associated protein 43 (Gap43) expression. SHPL-49 enhanced synaptic plasticity and increased Gap43 protein levels via activation of the BDNF pathway in the OGD primary neuron model. These results indicate that SHPL-49 prevents cerebral ischemic injury by activating neurotrophic factor pathways and altering microglial polarization. Thus, SHPL-49 is a potential neuroprotective agent.

PROTAC-biomacromolecule conjugates for precise protein degradation in cancer therapy: A review.

Proteolysis targeting chimera (PROTAC) technology is a promising new mode of targeted protein degradation with significant transformative implications for the clinical treatment of different diseases. Nevertheless, while this technology offers numerous advantages, on-target off-tumour toxicity in healthy cells remains a major challenge for clinical application in cancer therapy. Strategies are presently being explored to optimize degradation activity with cellular selectivity to minimize undesirable side effects. PROTAC-antibody conjugates and PROTAC-aptamer conjugates are unique innovations that combine PROTACs and biomacromolecules. These novel PROTAC-biomacromolecule conjugates (PBCs) can enhance the targetability of PROTACs and reduce their off-target side-effects. The combination of potent PROTACs and highly safe biomacromolecules will pioneer an emerging trend in targeted protein degradation. In our review, we have summarized recent advances in PBCs, discussed current challenges, and outlooked opportunities for future research in the field.

The role of TNC in atherosclerosis and drug development opportunities.

Tenascin C (TNC), a rich glycoprotein of the extracellular matrix, exhibits a pro-atherosclerosis or anti-atherosclerosis effect depending on its location. TNC, especially its C domain/isoform (TNC-C), is strongly overexpressed in atherosclerotic plaque active areas but virtually undetectable in most normal adult tissues, suggesting that TNC is a promising delivery vector target for atherosclerosis-targeted drugs. Many delivery vectors were investigated by recognizing TNC-C, including G11, G11-iRGD, TN11, PL1, and PL3. F16 and FNLM were also investigated by recognizing TNC-A1 and TNC, respectively. Notably, iRGD was undergoing clinical trials. PL1 not only recognizes TNC-C but also the extra domain-B (EDB) of fibronectin (FN), which is also a promising delivery vector for atherosclerosis-targeted drugs, and several conjugate agents are undergoing clinical trials. The F16-conjugate agent F16IL2 is undergoing clinical trials. Therefore, G11-iRGD, PL1, and F16 have great development value. Furthermore, ATN-RNA and IMA950 were investigated in clinical trials as therapeutic drugs and vaccines by targeting TNC, respectively. Therefore, targeting TNC could greatly improve the success rate of atherosclerosis-targeted drugs and/or specific drug development. This review discussed the role of TNC in atherosclerosis, atherosclerosis-targeted drug delivery vectors, and agent development to provide knowledge for drug development targeting TNC.

A novel nanobody-based HER2-targeting antibody exhibits potent synergistic antitumor efficacy in trastuzumab-resistant cancer cells.

Human epithelial growth factor receptor-2 (HER2) plays an oncogenic role in numerous tumors, including breast, gastric, and various other solid tumors. While anti-HER2 therapies are approved for the treatment of HER2-positive tumors, a necessity persists for creating novel HER2-targeted agents to resolve therapeutic resistance. Utilizing a synthetic nanobody library and affinity maturation, our study identified four anti-HER2 nanobodies that exhibited high affinity and specificity. These nanobodies recognized three distinct epitopes of HER2-ECD. Additionally, we constructed VHH-Fc and discovered that they facilitated superior internalization and showed moderate growth inhibition. Compared to the combination of trastuzumab and pertuzumab, the VHH-Fc combos or their combination with trastuzumab demonstrated greater or comparable antitumor activity in both ligand-independent and ligand-driven tumors. Most remarkably, A9B5-Fc, which targeted domain I of HER2-ECD, displayed significantly enhanced trastuzumab-synergistic antitumor efficacy compared to pertuzumab under trastuzumab-resistant conditions. Our findings offer anti-HER2 nanobodies with high affinity and non-overlapping epitope recognition. The novel nanobody-based HER2-targeted antibody, A9B5-Fc, binding to HER2-ECD I, mediates promising receptor internalization. It possesses the potential to serve as a potent synergistic partner with trastuzumab, contributing to overcoming acquired resistance.

Epidermal growth factor receptor dual-target inhibitors as a novel therapy for cancer: A review.

Overexpression of the epidermal growth factor receptor (EGFR) has been linked to several human cancers, including esophageal cancer, pancreatic cancer, anal cancer, breast cancer, and lung cancer, particularly non-small cell lung cancer (NSCLC). Therefore, EGFR has emerged as a critical target for treating solid tumors. Many 1st-, 2nd-, 3rd-, and 4th-generation EGFR single-target inhibitors with clinical efficacy have been designed and synthesized in recent years. Drug resistance caused by EGFR mutations has posed a significant challenge to the large-scale clinical application of EGFR single-target inhibitors and the discovery of novel EGFR inhibitors. Therapeutic methods for overcoming multipoint EGFR mutations are still needed in medicine. EGFR dual-target inhibitors are more promising than single-target inhibitors as they have a lower risk of drug resistance, higher efficacy, lower dosage, and fewer adverse events. EGFR dual-target inhibitors have been developed sequentially to date, providing new options for remission in patients with previously untreatable malignancies and laying the groundwork for a future generation of compounds. This paper introduces the EGFR family proteins and their synergistic effects with other anticancer targets, and provides a comprehensive review of the development of EGFR dual-target inhibitors in cancer, as well as the opportunities and challenges associated with those fields.

The role of CDR1as/ciRS-7 in cardio-cerebrovascular diseases.

Cerebellar degeneration-related protein 1 antisense RNA (CDR1as), also known as ciRS-7, is a circular natural antisense transcript of CDR1. It is a widely studied and powerful representative of circular RNAs. Based on its widely reported role in cancer, CDR1as is considered one of the most promising biomarkers for diagnosing and treating tumours. However, some recent studies have extensively focused on its regulatory role in cardio-cerebrovascular diseases instead of in tumours. Studies have shown that CDR1as plays a unique role in the occurrence of cardio-cerebrovascular diseases; thus, it may be a potential target for preventing and treating cardio-cerebrovascular diseases. Furthermore, CDR1as has also been found to be related to signal transduction pathways related to inflammatory response, oxidative stress, etc., which may reveal its potential mechanism in cardio-cerebrovascular diseases. However, there is no literature to summarize the role and possible mechanism of CDR1as in cardio-cerebrovascular diseases. Therefore, in the present review, we have comprehensively summarised the latest progress in the biological characteristics, development processes, regulatory mechanisms, and roles of CDR1as in cardio-cerebrovascular diseases, aiming to provide a reference and guidance for future studies.

Unlocking the potential of targeting histone-modifying enzymes for treating IBD and CRC.

Dysregulation of histone modifications has been implicated in the pathogenesis of both inflammatory bowel disease (IBD) and colorectal cancer (CRC). These diseases are characterized by chronic inflammation, and alterations in histone modifications have been linked to their development and progression. Furthermore, the gut microbiota plays a crucial role in regulating immune responses and maintaining gut homeostasis, and it has been shown to exert effects on histone modifications and gene expression in host cells. Recent advances in our understanding of the roles of histone-modifying enzymes and their associated chromatin modifications in IBD and CRC have provided new insights into potential therapeutic interventions. In particular, inhibitors of histone-modifying enzymes have been explored in clinical trials as a possible therapeutic approach for these diseases. This review aims to explore these potential therapeutic interventions and analyze previous and ongoing clinical trials that examined the use of histone-modifying enzyme inhibitors for the treatment of IBD and CRC. This paper will contribute to the current body of knowledge by exploring the latest advances in the field and discussing the limitations of existing approaches. By providing a comprehensive analysis of the potential benefits of targeting histone-modifying enzymes for the treatment of IBD and CRC, this review will help to inform future research in this area and highlight the significance of understanding the functions of histone-modifying enzymes and their associated chromatin modifications in gastrointestinal disorders for the development of potential therapeutic interventions.

Pro­angiogenic activity of salvianolate and its potential therapeutic effect against acute cerebral ischemia.

Salvianolate (Sal) is a medicinal composition that is widely used in China for the treatment of coronary heart disease and angina pectoris. The aim of the present study was to investigate the potential macrophage-mediated pro-angiogenic effects of Sal in vitro. In addition, another aim was to explore the effects of Sal in a rat model of transient middle cerebral artery occlusion (tMCAO) along with the potential mechanism by which it promotes angiogenesis. In this study, human umbilical vein endothelial cells (HUVECs) and Raw264.7 macrophages in vitro, and a rat tMCAO model in vivo were used to detect the pro-angiogenic effect and mechanism of Sal. The results of in vitro experiments showed that the viability, migration and tube formation of HUVECs were promoted by the supernatant of Sal-treated Raw264.7 macrophages (s-Sal) but not by Sal alone. s-Sal also increased the levels of phosphorylated (p-)VEGFR-2, p-AKT and p-p38 MAPK in HUVECs while Sal alone did not. In vivo, treatment with Sal significantly reduced the cerebral infarction volume and neurological deficit scores in the rat tMCAO model. Similar to the mechanism observed in the in vitro experiments, Sal treatment upregulated the protein expression of VEGF and VEGFR-2, in addition to the phosphorylation of VEGFR-2, AKT and p38, in the brain tissues of the tMCAO model rats. In summary, the results of the present study suggest that the mechanism of Sal-mediated angiogenesis is associated with stimulation of the VEGF/VEGFR-2 signaling pathway by macrophages. This suggests the potential of Sal as a therapeutic option for the treatment of acute cerebral ischemic injury, which may act via the promotion of angiogenesis.

Growth differentiation factor 11: A new hope for the treatment of cardiovascular diseases.

Growth differentiation factor 11 (GDF11) is a member of the transforming growth factor-ß superfamily that has garnered significant attention due to its anti-cardiac aging properties. Many studies have revealed that GDF11 plays an indispensable role in the onset of cardiovascular diseases (CVDs). Consequently, it has emerged as a potential target and novel therapeutic agent for CVD treatment. However, currently, no literature reviews comprehensively summarize the research on GDF11 in the context of CVDs. Therefore, herein, we comprehensively described GDF11's structure, function, and signaling in various tissues. Furthermore, we focused on the latest findings concerning its involvement in CVD development and its potential for clinical translation as a CVD treatment. We aim to provide a theoretical basis for the prospects and future research directions of the GDF11 application regarding CVDs.

The potential role and mechanism of circRNA/miRNA axis in cholesterol synthesis.

Cholesterol levels are an initiating risk factor for atherosclerosis. Many genes play a central role in cholesterol synthesis, including HMGCR, SQLE, HMGCS1, FDFT1, LSS, MVK, PMK, MVD, FDPS, CYP51, TM7SF2, LBR, MSMO1, NSDHL, HSD17B7, DHCR24, EBP, SC5D, DHCR7, IDI1/2. Especially, HMGCR, SQLE, FDFT1, LSS, FDPS, CYP51, and EBP are promising therapeutic targets for drug development due to many drugs have been approved and entered into clinical research by targeting these genes. However, new targets and drugs still need to be discovered. Interestingly, many small nucleic acid drugs and vaccines were approved for the market, including Inclisiran, Patisiran, Inotersen, Givosiran, Lumasiran, Nusinersen, Volanesorsen, Eteplirsen, Golodirsen, Viltolarsen, Casimersen, Elasomeran, Tozinameran. However, these agents are all linear RNA agents. Circular RNAs (circRNAs) may have longer half-lives, higher stability, lower immunogenicity, lower production costs, and higher delivery efficiency than these agents due to their covalently closed structures. CircRNA agents are developed by several companies, including Orna Therapeutics, Laronde, and CirCode, Therorna. Many studies have shown that circRNAs regulate cholesterol synthesis by regulating HMGCR, SQLE, HMGCS1, ACS, YWHAG, PTEN, DHCR24, SREBP-2, and PMK expression. MiRNAs are essential for circRNA-mediated cholesterol biosynthesis. Notable, the phase II trial for inhibiting miR-122 with nucleic acid drugs has been completed. Suppressing HMGCR, SQLE, and miR-122 with circRNA_ABCA1, circ-PRKCH, circEZH2, circRNA-SCAP, and circFOXO3 are the promising therapeutic target for drug development, specifically the circFOXO3. This review focuses on the role and mechanism of the circRNA/miRNA axis in cholesterol synthesis in the hope of providing knowledge to identify new targets.

Marine Sulfated Polysaccharide PMGS Synergizes with Paclitaxel in Inhibiting Cervical Cancer In Vitro.

The incidence and mortality of cervical cancer in female malignancies are second only to breast cancer, which brings a heavy health and economic toll worldwide. Paclitaxel (PTX)-based regimens are the first-class choice; however, severe side effects, poor therapeutic effects, and difficulty in effectively preventing tumor recurrence or metastasis are unavoidable. Therefore, it is necessary to explore effective therapeutic interventions for cervical cancer. Our previous studies have shown that PMGS, a marine sulfated polysaccharide, exhibits promising anti-human papillomavirus (anti-HPV) effects through multiple molecular mechanisms. In this article, a continuous study identified that PMGS, as a novel sensitizer, combined with PTX exerted synergistic anti-tumor effects on cervical cancer associated with HPV in vitro. Both PMGS and PTX inhibited the proliferation of cervical cancer cells, and the combination of PMGS with PTX displayed significant synergistic effects on Hela cells. Mechanistically, PMGS synergizes with PTX by enhancing cytotoxicity, inducing cell apoptosis and inhibiting cell migration in Hela cells. Collectively, the combination of PTX and PMGS potentially provides a novel therapeutic strategy for cervical cancer.

Multi-pathway neuroprotective effects of a novel salidroside derivative SHPL-49 against acute cerebral ischemic injury.

SHPL-49 ((2R,3S,4S,5R,6R)-2-(hydroxymethyl)-6-(4-(4-methoxyphenyl) butoxy) tetrahydro-2H-pyran-3,4,5-triol) is a novel glycoside derivative obtained from structural modification of salidroside, which is isolated from the medicinal plant Rhodiola rosea L. SHPL-49 was administered to rats with permanent middle cerebral artery occlusion (pMCAO) for 5 days, and it was found that SHPL-49 could alleviate the cerebral infarct volume and reduce the neurological deficit score. Moreover, the effective time window of SHPL-49 in the pMCAO model was from 0.5 to 8 h after embolization. In addition, the result of immunohistochemistry showed that SHPL-49 could increase the number of neurons in the brain tissue and reduce the occurrence of apoptosis. Morris water maze and Rota-rod experiments showed that SHPL-49 could improve neurological deficits, repair neurocognitive and motor dysfunction, and enhance learning and memory ability in the pMCAO model after 14 days of SHPL-49 treatment. Further in vitro experiments showed that SHPL-49 significantly reduced the calcium overload of PC-12 cells and the production of reactive oxygen species (ROS) induced by oxygen and glucose deprivation (OGD), and increased the levels of antioxidant enzymes superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px), decreased the production of malondialdehyde (MDA). Furthermore, SHPL-49 could reduce cell apoptosis by increasing protein expression ratio of anti-apoptotic factor Bcl-2 to pro-apoptotic factor Bax in vitro. SHPL-49 also regulated the expression of Bcl-2 and Bax in ischemic brain tissue, and even inhibited the caspase cascade of pro-apoptotic proteins Cleaved-caspase 9 and Cleaved-caspase 3. Taken together, SHPL-49 exhibited neuroprotective effects against cerebral ischemic injury through multiple pathways, such as alleviating calcium overload, reducing oxidative stress damage, and inhibiting apoptosis.

MST1: A future novel target for cardiac diseases.

Major heart diseases pose a serious threat to human health. Finding early diagnostic markers and key therapeutic targets is an urgent scientific problem in this field. Mammalian sterile 20-like kinase 1 (MST1) is a protein kinase, and the occurrence of many heart diseases is related to the continuous activation of the MST1 gene. With the deepening of the research, the potential role of MST1 in promoting the development of heart disease has become more apparent. Therefore, to better understand the role of MST1 in the pathogenesis of heart disease, this work systematically summarizes the role of MST1 in the pathogenesis of heart disease, gives a comprehensive overview of its possible strategies in the diagnosis and treatment of heart disease, and analyzes its potential significance as a marker for the diagnosis and treatment of heart disease.

Protective effect and underlying mechanism of muscone on acute cerebral ischemia-reperfusion injury in rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Musk is a widely used traditional Chinese medicine, which has resuscitation, activating blood, and disperse swelling effects. Musk is commonly used in the prevention of myocardial infarction and ischemic stroke, and muscone is its main active component. AIM OF THE STUDY: The effect and mechanism of muscone to improve the condition of ischemic stroke is not clear, accordingly, we verified its efficacy in ischemia-reperfused rats, and investigated its mechanism by PC12 and THP-1 cells. METHODS: A transient middle cerebral artery occlusion (tMCAO) rat model was established for in vivo experiments. 2,3,5-Triphenyl Tetrazolium Chloride (TTC) staining was used to calculate infarct rate. Neuroprotection and angiogenesis were assessed by Hematoxylin-eosin (HE) staining, nissl staining, immunofluorescence staining, and quantitative real-time PCR (qRT-PCR). Oxygen glucose deprivation-reperfusion (OGD/R) model of PC12 cells was established for neuroprotection analysis, where CCK-8 assay was used to measure cell viability, flow cytometry and Hoechst 33258 staining were used to demonstrate apoptosis, and protein levels were detected by Western blot. For angiogenesis analysis, enzyme-linked immunosorbent assay (ELISA) and qRT-PCR were used to detect angiogenic factors expressed by THP-1. Cell viability assay, scratch wound assay, and tube formation assay were used to evaluate angiogenic effect of HUVECs treated with medium of THP-1. And the angiogenic pathway in HUVECs was detected by Western blot. RESULTS: According to the results, in cerebral ischemia-reperfusion rats, the infarct rate and tissue damage were significantly reduced by muscone, and the expression of neurotrophic factors and angiogenesis-related factors were all elevated. In OGD/R-PC12 cell models, muscone could increase cell viability and inhibit apoptosis via Bax/Bcl-2/Caspase-3 pathway. In THP-1-mediated angiogenesis of HUVECs, muscone promoted the secretion of angiogenesis-related factors in THP-1 and thus indirectly promoted the proliferation, migration and tube formation of HUVECs, and then regulated phosphorylation of VEGFR2 and Akt in HUVECs. CONCLUSIONS: Our study indicated that muscone may be a potential neuroprotective and proangiogenic agent in cerebral ischemia.

The clinical development of antibody-drug conjugates for non-small cell lung cancer therapy.

Despite the emergence of molecular targeted therapy and immune checkpoint inhibitors as standard first-line treatments for non-small cell lung cancer (NSCLC), their efficacy in some patients is limited by intrinsic and acquired resistance. Antibody-drug conjugates (ADCs), a revolutionary class of antitumor drugs, have displayed promising clinical outcomes in cancer treatment. In 2022, trastuzumab deruxtecan (Enhertu) was approved for treating HER2-mutated NSCLC, thereby underscoring the clinical value of ADCs in NSCLC treatment strategies. An increasing number of ADCs, focusing on NSCLC, are undergoing clinical trials, potentially positioning them as future treatment options. In this review, we encapsulate recent advancements in the clinical research of novel ADCs for treating NSCLC. Subsequently, we discuss the mechanisms of action, clinical efficacy, and associated limitations of these ADCs.