Inflammatory and autoimmune disorders, characterized by dysregulated immune responses leading to tissue damage and chronic inflammation, present significant health challenges. This review uniquely focuses on efferocytosis-the phagocyte-mediated clearance of apoptotic cells-and its pivotal role in these disorders. We delve into the intricate mechanisms of efferocytosis\' four stages and their implications in disease pathogenesis, distinguishing our study from previous literature. Our findings highlight impaired efferocytosis in conditions like atherosclerosis and asthma, proposing its targeting as a novel therapeutic strategy. We discuss the therapeutic potential of efferocytosis in modulating immune responses and resolving inflammation, offering a new perspective in treating inflammatory disorders.

In recent decades, the field of systemic cancer treatment has seen remarkable changes due to advancements in the understanding of cancer\'s biology, immunology, and genetic makeup. As a result, individuals with late-stage cancers are now achieving survival rates that were previously unattainable. The goal of personalized cancer therapy is to enhance clinical outcomes by customizing drug treatments to suit the unique genetic and/or epigenetic profiles of each patient\'s tumor. This approach aims to reduce the side effects commonly associated with ineffective treatments. Advances in genetic sequencing and molecular cytogenetics have been instrumental in identifying cancer-driving mutations and epigenetic irregularities, leading to the development of specific molecular therapies. This review article highlights the progress and success of targeted molecular therapies in treating malignant melanoma, illustrating the concept of personalized cancer treatment.

UNASSIGNED: To establish a modified nomogram model for pancreatic neuroendocrine carcinoma (pNEC) patients with liver metastasis via single-center clinical data, and to provide guidelines for improving the diagnosis and treatment of patients.
UNASSIGNED: A retrospective analysis of clinical data from pNEC patients with liver metastasis at Peking Union Medical College Hospital (January 2000 to November 2023) was conducted. Univariate and multivariate Cox regression analyses were employed to identify prognostic factors for overall survival (OS). Kaplan-Meier curves were generated, and a modified nomogram predictive model was developed to illustrate the prognosis of pNEC patients with liver metastasis. Calibration plots and C-index were used to validate the model\'s feasibility, accuracy, and reliability.
UNASSIGNED: Forty-five participants with the rare cancer type pNEC and liver metastasis were included in the study. Kaplan-Meier curves revealed that primary tumor resection (PTR), chemotherapy or targeted therapy, and tumor size equal to or less than 5cm significantly improved OS compared to those without PTR, chemotherapy or targeted therapy, and tumor size larger than 5cm. Multivariate Cox regression analysis identified PTR, a combination of chemotherapy and targeted therapy, and tumor size as independent prognostic factors for OS. The predictive nomogram model exhibited acceptable performance with a C-index of 0.744 (0.639-0.805) through bootstrapping.
UNASSIGNED: Combining chemotherapy with targeted therapy enhances the survival of pNEC patients with liver metastasis. The modified nomogram model and predictive score table offer valuable references and insights for both clinicians and patients.

Even with sufficient oxygen, tumor cells use glycolysis to obtain the energy and macromolecules they require to multiply, once thought to be a characteristic of tumor cells known as the \"Warburg effect\". In fact, throughout the process of carcinogenesis, immune cells and stromal cells, two major cellular constituents of the tumor microenvironment (TME), also undergo thorough metabolic reprogramming, which is typified by increased glycolysis. In this review, we provide a full-scale review of the glycolytic remodeling of several types of TME cells and show how these TME cells behave in the acidic milieu created by glucose shortage and lactate accumulation as a result of increased tumor glycolysis. Notably, we provide an overview of putative targets and inhibitors of glycolysis along with the viability of using glycolysis inhibitors in combination with immunotherapy and chemotherapy. Understanding the glycolytic situations in diverse cells within the tumor immunological milieu will aid in the creation of subsequent treatment plans.

UNASSIGNED: Targeted therapy for Sjögren\'s syndrome (SS) has become an important focus for clinicians. Multi-omics-wide Mendelian randomization (MR) analyses have provided new ideas for identifying potential drug targets.
UNASSIGNED: We conducted summary-data-based Mendelian randomization (SMR) analysis to evaluate therapeutic targets associated with SS by integrating DNA methylation, gene expression and protein quantitative trait loci (mQTL, eQTL, and pQTL, respectively). Genetic associations with SS were derived from the FinnGen study (discovery) and the GWAS catalog (replication). Colocalization analyses were employed to determine whether two potentially relevant phenotypes share the same genetic factors in a given region. Moreover, to delve deeper into potential regulation among DNA methylation, gene expression, and protein abundance, we conducted MR analysis to explore the causal relationship between candidate gene methylation and expression, as well as between gene expression and protein abundance. Drug prediction and molecular docking were further employed to validate the pharmacological activity of the candidate drug targets.
UNASSIGNED: Upon integrating the multi-omics data, we identified three genes associated with SS risk: TNFAIP3, BTN3A1, and PLAU. The methylation of cg22068371 in BTN3A1 was positively associated with protein levels, consistent with the negative effect of cg22068371 methylation on the risk of SS. Additionally, positive correlations were observed between the gene methylation of PLAU (cg04939496) and expression, as well as between expression and protein levels. This consistency elucidates the promotional effects of PLAU on SS risk at the DNA methylation, gene expression, and protein levels. At the protein level, genetically predicted TNFAIP3 (OR 2.47, 95% CI 1.56-3.92) was positively associated with SS risk, while BTN3A1 (OR 2.96E-03, 95% CI 2.63E-04-3.33E-02) was negatively associated with SS risk. Molecular docking showed stable binding for candidate drugs and target proteins.
UNASSIGNED: Our study reveals promising therapeutic targets for the treatment of SS, providing valuable insights into targeted therapy for SS. However, further validation through future experiments is warranted.

Atherosclerosis continues to be a leading cause of morbidity and mortality globally. The precise evaluation of the extent of an atherosclerotic plaque is essential for forecasting its likelihood of causing health concerns and tracking treatment outcomes. When compared to conventional methods used, nanoparticles offer clear benefits and excellent development opportunities for the detection and characterisation of susceptible atherosclerotic plaques. In this review, we analyse the recent advancements of nanoparticles as theranostics in the management of atherosclerosis, with an emphasis on applications in drug delivery. Furthermore, the main issues that must be resolved in order to advance clinical utility and future developments of NP research are discussed. It is anticipated that medical NPs will develop into complex and advanced next-generation nanobotics that can carry out a variety of functions in the bloodstream.

Tau protein is a microtubule-associated protein that is widely distributed in the central nervous system and maintains and regulates neuronal morphology and function. Tau protein aggregates abnormally and forms neurofibrillary tangles in neurodegenerative diseases, disrupting the structure and function of neurons and leading to neuronal death, which triggers the initiation and progression of neurological disorders. The aggregation of tau protein in neurodegenerative diseases is associated with post-translational modifications, which may affect the hydrophilicity, spatial conformation, and stability of tau protein, promoting tau protein aggregation and the formation of neurofibrillary tangles. Therefore, studying the role of tau protein in neurodegenerative diseases and the mechanism of aberrant aggregation is important for understanding the mechanism of neurodegenerative diseases and finding therapeutic approaches. This review describes the possible mechanisms by which tau protein promotes neurodegenerative diseases, the post-translational modifications of tau protein and associated influencing factors, and the current status of drug discovery and development related to tau protein, which may contribute to the development of new therapeutic approaches to alleviate or treat neurodegenerative diseases.

Including poly(ADP-ribose) polymerase (PARP) inhibitors in managing patients with inoperable tumors has significantly improved outcomes. The PARP inhibitors hamper single-strand deoxyribonucleic acid (DNA) repair by trapping poly(ADP-ribose)polymerase (PARP) at sites of DNA damage, forming a non-functional \"PARP enzyme-inhibitor complex\" leading to cell cytotoxicity. The effect is more pronounced in the presence of PARP upregulation and homologous recombination (HR) deficiencies such as breast cancer-associated gene (BRCA1/2). Hence, identifying HR-deficiencies by genomic analysis-for instance, BRCA1/2 used in triple-negative breast cancer-should be a part of the selection process for PARP inhibitor therapy. Published data suggest BRCA1/2 germline mutations do not consistently predict favorable responses to PARP inhibitors, suggesting that other factors beyond tumor mutation status may be at play. A variety of factors, including tumor heterogeneity in PARP expression and intrinsic and/or acquired resistance to PARP inhibitors, may be contributing factors. This justifies the use of an additional tool for appropriate patient selection, which is noninvasive, and capable of assessing whole-body in vivo PARP expression and evaluating PARP inhibitor pharmacokinetics as complementary to the currently available BRCA1/2 analysis. In this review, we discuss [18F]Fluorine PARP inhibitor radiotracers and their potential in the imaging of PARP expression and PARP inhibitor pharmacokinetics. To provide context we also briefly discuss possible causes of PARP inhibitor resistance or ineffectiveness. The discussion focuses on TNBC, which is a tumor type where PARP inhibitors are used as part of the standard-of-care treatment strategy.

Renal cell carcinoma (RCC) remains incurable in advanced stages. Biomarkers have proven to be quite useful in cancer therapeutics. Herein, we provide a comparative/integrative statistical analysis of seminal immunohistochemistry (IHC) findings for Wilms\' Tumor 1 antigen (WT1) and thymine dimers (TDs), emerging as atypical, yet promising, potential biomarkers for RCCs. We assessed WT1/TD reactivity in adult RCC tumor cells, tumor microenvironment (TME), and tumor-adjacent healthy renal tissue (HRT). WT1 positivity was scarce and strictly nuclear in tumor cells, whereas TD-reactive tumor tissues were prevalent. We report statistically significant positive correlations between the density of reactive RCC cellularity and the intensity of nuclear staining for both biomarkers (WT1 - rho = 0.341, p-value = 0.036; TDs - rho = 0.379, p-value = 0.002). RCC stromal TME TD-positivity was much more frequent than WT1 reactivity, apparently proportional to that of the proper RCC cellularity and facilitated by extensive RCC inflammatory infiltration. TDs exhibited nuclear reactivity for most TME cell lines, while RCC TME WT1 expression was rare and inconsistent. In HRTs, TDs were entirely restricted to renal tubular cells, the likely cellular progenitor of most conventional RCC subtypes. In lieu of proper validation, these early findings have significant implications regarding the origins/biology of RCCs and may inform RCC therapeutics, both accounting for the high frequency of immunotherapy-permissive frameshift indels in RCCs, but also hinting at novel predictive clinical tools for WT1-targeted immunotherapy. Overall, the current study represents a meek yet hopefully significant step towards understanding the molecular biology and potential therapeutic targets of RCCs.

In drug development, it is not uncommon that an active substance exhibits efficacy in vitro but lacks the ability to specifically reach its target in vivo. As a result, targeted drug delivery has become a primary focus in the pharmaceutical sciences. Since the approval of Doxil® in 1995, liposomes have emerged as a leading nanoparticle in targeted drug delivery. Their low immunogenicity, high versatility, and well-documented efficacy have led to their clinical use against a wide variety of diseases. That being said, every disease is accompanied by a unique set of physiological conditions, and each liposomal product must be formulated with this consideration. There are a multitude of different targeting techniques for liposomes that can be employed depending on the application. Passive techniques such as PEGylation or the enhanced permeation and retention effect can improve general pharmacokinetics, while active techniques such as conjugating targeting molecules to the liposome surface may bring even further specificity. This review aims to summarize the current strategies for targeted liposomes in the treatment of diseases.