Cardiovascular diseases (CVDs) have a complex pathogenesis and pose a major threat to human health. Cardiomyocytes have a low regenerative capacity, and their death is a key factor in the morbidity and mortality of many CVDs. Cardiomyocyte death can be regulated by specific signaling pathways known as programmed cell death (PCD), including apoptosis, necroptosis, autophagy, pyroptosis, and ferroptosis, etc. Abnormalities in PCD can lead to the development of a variety of cardiovascular diseases, and there are also molecular-level interconnections between different PCD pathways under the same cardiovascular disease model. Currently, the link between programmed cell death in cardiomyocytes and cardiovascular disease is not fully understood. This review describes the molecular mechanisms of programmed death and the impact of cardiomyocyte death on cardiovascular disease development. Emphasis is placed on a summary of drugs and potential therapeutic approaches that can be used to treat cardiovascular disease by targeting and blocking programmed cell death in cardiomyocytes.

UNASSIGNED: Osteoarthritis (OA) related pain has affected millions of people worldwide. However, the current pharmacological options for managing OA-related pain have not achieved a satisfactory effect.
UNASSIGNED: This narrative review provides an overview of the current and emerging drugs for OA-related pain. It covers the drugs\' mechanism of action, safety, efficacy, and limitations. The National Library of Medicine (PubMed) database was primarily searched from 2000 to 2024.
UNASSIGNED: Current treatment options are limited and suboptimal for OA pain management. Topical nonsteroidal anti-inflammatory drugs (NSAIDs) are the recognized and first-line treatment in the management of OA-related pain, and other drugs are inconsistent recommendations by guidelines. Emerging treatment options are promising for OA-related pain, including nerve growth factor (NGF) inhibitors, ion channel inhibitors, and calcitonin gene-related peptide (CGRP) antagonists. Besides, drugs repurposing from antidepressants and antiepileptic analgesics are shedding light on the management of OA-related pain. The management of OA-related pain is challenging as pain is heterogeneous and subjective. A more comprehensive strategy combined with non-pharmacological therapy needs to be considered, and tailored management options to individualized patients.

Platinum (II) drugs, including cisplatin, carboplatin, and oxaliplatin, have achieved significant clinical success in cancer treatment. However, their clinical application has been greatly hindered by various adverse factors such as non-specific activation and drug resistance. Compared with Pt(II) drugs, the axial ligands within Pt(IV) compounds can improve the pharmacokinetic properties, selectivity, and biological activity, implementing alternative cytotoxic mechanisms beyond DNA cross-linking and partially overcoming drug resistance. The controlled conversion of Pt(IV) prodrugs into Pt(II) agents at the tumor site has been extensively explored internationally. In this review, Pt(IV) prodrug modification strategies are first summarized, next the development of the predominant external and internal photosensitizers is listed. Finally, three representative photoreduction mechanisms and strategies for developing corresponding Pt(IV) prodrugs are discussed. This work provides constructive instruction for the subsequent molecular design of Pt(IV) prodrugs.

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Systemic lupus erythematosus (SLE) is an intricate autoimmune disease with diverse manifestations. Immunometabolism reprogramming contributes to the progression of SLE by regulating the phenotype and function of immune cells. Dysregulated iron metabolism is implicated in SLE pathogenesis, affecting both systemic and immune cell-specific iron homeostasis. This review explores the systemic and cellular iron handling and regulation. Additionally, the advancements regarding iron metabolism in SLE with a focus on the distinct subsets of immune cells are highlighted. By gaining insight into the interplay between iron dysregulation and immune dysfunction, the potential therapeutic avenues may be unveiled. However, challenges remain in elucidating cell-specific iron metabolic reprogramming and its contribution to SLE pathogenesis needs further research for personalized therapeutic interventions and biomarker discovery. This review provides an in-depth understanding of immune cell-specific regulatory mechanisms of iron metabolism and new insights in current challenges as well as possible clinical applications.

UNASSIGNED: Acanthamoeba infection is a serious public health concern, necessitating the development of effective and safe anti-Acanthamoeba chemotherapies. Poly (ADP-ribose) polymerases (PARPs) govern a colossal amount of biological processes, such as DNA damage repair, protein degradation and apoptosis. Multiple PARP-targeted compounds have been approved for cancer treatment. However, repurposing of PARP inhibitors to treat Acanthamoeba is poorly understood.
UNASSIGNED: In the present study, we attempted to fill these knowledge gaps by performing anti-Acanthamoeba efficacy assays, cell biology experiments, bioinformatics, and transcriptomic analyses.
UNASSIGNED: Using a homology model of Acanthamoeba poly (ADP-ribose) polymerases (PARPs), molecular docking of approved drugs revealed three potential inhibitory compounds: olaparib, venadaparib and AZ9482. In particular, venadaparib exhibited superior docking scores (-13.71) and favorable predicted binding free energy (-89.28 kcal/mol), followed by AZ9482, which showed a docking score of -13.20 and a binding free energy of -92.13 kcal/mol. Notably, the positively charged cyclopropylamine in venadaparib established a salt bridge (through E535) and a hydrogen bond (via N531) within the binding pocket. For comparison, AZ9482 was well stacked by the surrounding aromatic residues including H625, Y652, Y659 and Y670. In an assessment of trophozoites viability, AZ9482 exhibited a dose-and time-dependent anti-trophozoite effect by suppressing Acanthamoeba PARP activity, unlike olaparib and venadaparib. An Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis assay revealed AZ9482 induced trophozoite necrotic cell death rather than apoptosis. Transcriptomics analyses conducted on Acanthamoeba trophozoites treated with AZ9482 demonstrated an atlas of differentially regulated proteins and genes, and found that AZ9482 rapidly upregulates a multitude of DNA damage repair pathways in trophozoites, and intriguingly downregulates several virulent genes. Analyzing gene expression related to DNA damage repair pathway and the rate of apurinic/apyrimidinic (AP) sites indicated DNA damage efficacy and repair modulation in Acanthamoeba trophozoites following AZ9482 treatment.
UNASSIGNED: Collectively, these findings highlight AZ9482, as a structurally unique PARP inhibitor, provides a promising prototype for advancing anti-Acanthamoeba drug research.

Functionalized graphene oxide nanoparticles (NPs) have emerged as promising nanocarriers for drug delivery in lung cancer therapy. Quercetin and lurbinectedin encapsulated in graphene oxide (GO) NPs are tested for treating A549 lung cancer cells. Spectroscopic analyses show that graphene oxide functionalization creates a transparent, smooth surface for drug loading. Treatment with quercetin/lurbinectedin-loaded GO NPs induces notable cytotoxic effects in lung cancer cells, as evidenced by distinct morphological alterations and confirmed apoptotic cellular death observed through fluorescence microscopy. Additionally, our study highlights the impact of this approach on lung cancer metastasis, supported by qRT-PCR analysis of relative gene expression levels, including p53, Bax, Caspase-3, and Bcl 2, revealing robust molecular mechanisms underlying therapeutic efficacy against A549 and PC9 cell lines. Flow cytometric analyses further confirm the induction of cellular death in lung cancer cells following administration of the nanoformulation. Our findings show that quercetin/lurbinectedin-loaded GO NPs may be a promising lung cancer treatment, opening new avenues for targeted and effective therapies.

Drug-induced dermatomyositis (DIDM) is a rare and underestimated variant of dermatomyositis (DM) characterized by muscle damage and skin rash and related to certain drug exposure. The spectrum of drugs causing DIDM has evolved over time, originally implicating hydroxyurea, penicillamine, and statins as causative agents. Tumor necrosis factor α inhibitors and immune checkpoint inhibitors have also been associated with such conditions. To bridge the gap between current literature and clinical practice, and therefore guide clinicians, we conducted a comprehensive review of English literature from Pubmed, EMBASE, and MEDLINE. Our analysis included demographic data, clinical features, laboratory findings, therapeutic outcomes, and extant research pertaining to the probable pathogenesis of DIDM induced by various drugs. Furthermore, we categorized the drugs involved in DIDM cases into biologics and traditional agents for subsequent statistical analysis. Over time, there has been a gradual accumulation of reported DIDM cases. A total of 69 published DIDM cases were documented in our study, among which 33 should be attributed to biologics and the remaining 36 to traditional drugs. Interestingly, 41 of all DIDM cases had a previous history of malignancies. Additionally, DIDM cases exhibited similar cutaneous and muscular manifestations to classic DM, with the exception of cases induced by hydroxyurea, which did not entail muscle damage. Positive antinuclear antibodies and anti-TIF1-γ autoantibodies have been predominantly observed in biologics-induced cases, while positive anti-TIF1-γ antibodies were merely reported in the cases that were primarily diagnosed with malignant diseases and exposed to ICIs afterwards. Anti-TIF1-γ antibodies may potentially serve as a red flag in the identification of co-existing malignant diseases in DM patients. We also provided a comprehensive summary and exploration of potential mechanisms lying behind drug-induced dermatomyositis. In conclusion, our review consolidates the current literature on DIDM, highlighting the evolving spectrum of medications and elucidating the differences in clinical manifestations, laboratory findings, and underlying mechanisms.

Primary biliary cholangitis (PBC) and primary sclerosing cholangitis (PSC) are autoimmune disorders characterized by progressive and chronic damage to the bile ducts, presenting clinicians with significant challenges. The objective of this study is to identify potential druggable targets to offer new avenues for treatment. A Mendelian randomization analysis was performed to identify druggable targets for PBC and PSC. This involved obtaining Cis-protein quantitative trait loci (Cis-pQTL) data from the deCODE database to serve as exposure. Outcome data for PBC (557 cases and 281,127 controls) and PSC (1,715 cases and 330,903 controls) were obtained from the FINNGEN database. Colocalization analysis was conducted to determine whether these features share the same associated SNPs. Validation of the expression level of druggable targets was done using the GSE119600 dataset and immunohistochemistry for clinical samples. Lastly, the DRUGBANK database was used to predict potential drugs. The MR analysis identified eight druggable targets each for PBC and PSC. Subsequent summary-data-based MR and colocalization analyses showed that LEFTY2 had strong evidence as a therapeutic candidate for PBC, while HSPB1 had moderate evidence. For PSC, only FCGR3B showed strong evidence as a therapeutic candidate. Additionally, upregulated expression of these genes was validated in PBC and PSC groups by GEO dataset and clinical samples. This study identifies two novel druggable targets with strong evidence for therapeutic candidates for PBC (LEFTY2 and HSPB1) and one for PSC (FCGR3B). These targets offer new therapeutic opportunities to address the challenging nature of PBC and PSC treatment.

BACKGROUND: Low-dose chemotherapy is a promising treatment strategy that may be improved by controlled delivery.
OBJECTIVE: This study aimed to design polyethylene glycol-stabilized bilayer-decorated magnetic Cationic Liposomes (CLs) as a drug delivery system for integrated functional studies of lung cancer cell therapy and imaging.
METHODS: A novel multifunctional folic acid targeting magnetic CLs docetaxel drug-loading system (FA-CLs-Fe- DOC) was prepared and tested for its physical properties, encapsulation rate and drug release performance. The feasibility of FA-CLs-Fe-DOC ability to inhibit tumor cells and act as an MRI contrast agent was investigated in vitro, and the target recognition and therapeutic ability of FA-CLs-Fe-DOC was studied in vivo.
RESULTS: FA-CLs-Fe-DOC had a particle size of 221.54 ± 6.42 nm and a potential of 28.64 ± 3.56 mv, with superparamagnetic properties and better stability. The encapsulation rate was 95.36 ± 1.63%, and the drug loading capacity was 9.52 ± 0.22%, which possessed the drug slow-release performance and low cytotoxicity and could effectively inhibit the proliferation of lung cancer cells,promoting apoptosis of lung cancer cells. MRI showed that it had the function of tracking and localization of lung cancer cells. In vivo experiments confirmed the targeted recognition property and therapeutic function of lung cancer cells.
CONCLUSIONS: In this study, we successfully prepared an FA-CLs-Fe-DOC capable of specifically targeting lung cancer cells with integrated functions of efficient lung cancer cell killing and imaging localization. This targeted drug packaging technology may provide a new strategy for the design of integrated carriers for targeted cancer therapy and imaging.

Glycan-based scaffolds are unique in their high specificity, versatility, low immunogenicity, and ability to mimic natural carbohydrates, making them attractive candidates for use in cancer treatment. These scaffolds are made up of glycans, which are biopolymers with well biocompatibility in the human body that can be used for drug delivery. The versatility of glycan-based scaffolds allows for the modulation of drug activity and targeted delivery to specific cells or tissues, which increases the potency of drugs and reduces side effects. Despite their promise, there are still technical challenges in the design and production of glycan-based scaffolds, as well as limitations in their therapeutic efficacy and specificity.