a-surgical-method-for-subvalvular-structure-intervention-through

A Surgical Method for Subvalvular Structure Intervention Through a Transaortic Approach in Normal Bama Pigs

Subvalvular structure abnormalities leading to left ventricular outflow tract (LVOT) alterations and myocardial hypertrophy are characteristic anatomical ...

Renmin hospital of Wuhan university

Chinese Academy of Medical Sciences and Peking Union Medical College

Tumor immunotherapy is the fourth therapy after surgery, chemotherapy, and radiotherapy. It has made great breakthroughs in the treatment of some epithelial tumors and hematological tumors. However, its adverse reactions are common or even more serious, and the response rate in some solid tumors is not satisfactory. With the maturity of genomics and metabolomics technologies, the effect of intestinal microbiota in tumor development and treatment has gradually been recognized. The microbiota may affect tumor immunity by regulating the host immune system and tumor microenvironment. Some bacteria help fight tumors by activating immunity, while some bacteria mediate immunosuppression to help cancer cells escape from the immune system. More and more studies have revealed that the effects and complications of tumor immunotherapy are related to the composition of the gut microbiota. The composition of the intestinal microbiota that is sensitive to treatment or prone to adverse reactions has certain characteristics. These characteristics may be used as biomarkers to predict the prognosis of immunotherapy and may also be developed as "immune potentiators" to assist immunotherapy. Some clinical and preclinical studies have proved that microbial intervention, including microbial transplantation, can improve the sensitivity of immunotherapy or reduce adverse reactions to a certain extent. With the development of gene editing technology and nanotechnology, the design and development of engineered bacteria that contribute to immunotherapy has become a new research hotspot. Based on the relationship between the intestinal microbiota and immunotherapy, the correct mining of microbial information and the development of reasonable and feasible microbial intervention methods are expected to optimize tumor immunotherapy to a large extent and bring new breakthroughs in tumor treatment.

The Role of Gut Microbiota in Tumor Immunotherapy.

Inflammation and oxidative stress contribute to the progression of sepsis-induced acute lung injury (ALI). SAM domain, SH3 domain and nuclear localization signals 1 (SAMSN1) is a signaling adaptor protein, and mainly regulates inflammatory response of various immune cells. The present study generates macrophage-specific SAMSN1-knockout (Samsn1) and SAMSN1-transgenic (Samsn1) mice to investigate its role and mechanism in sepsis-induced ALI.

Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice.

Corrigendum to "Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice" [Redox Biol. 56 (2022) 102432].

Retraction notice to: Corrigendum to "Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice" [Redox Biol. 70 (2024) 103036].

Retraction notice to: Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice [Redox Biol. 56 (2022) 102432].

Although the understanding of sepsis has evolved from "sepsis 1.0" to "sepsis 3.0", and the consensus on clinical management of sepsis has been continuously updated, the incidence rate and mortality of sepsis remain high. Therefore, in-depth investigation of the pathogenesis and related influencing factors of sepsis is of great significance for revealing the nature of sepsis and improving the clinical outcome of sepsis patients. This review will focus on the key issues in the basic research of sepsis, and summarize the recent advances and challenges in this field, mainly including genetic polymorphism, microorganisms, high-mobility group box 1 (HMGB1), endothelial dysfunction, immunotherapy, and biomarkers, aiming to provide new insights for the diagnosis and treatment of sepsis.

[Basic research in sepsis: advances and challenges].

Sepsis-related organ dysfunction is associated with increased morbidity and mortality. Previous studies have found that the endothelium plays crucial roles in maintaining the vascular permeability during sepsis, as well as in regulating inflammation and thrombosis. During sepsis, endothelial cells may release cytokines, chemokines, and pro-coagulant factors, as well as express adhesion molecules. In general, endothelial responses during sepsis typically inhibit bacterial transmission and coordinate leukocyte recruitment to promote bacterial clearance. However, excessive or prolonged endothelial activation can lead to impaired microcirculation, tissue hypoperfusion, and organ dysfunction. Given the structural and functional heterogeneity of endothelial cells in different organs, there are potential differences in endothelial responses by organ type, and the risk of organ damage may vary accordingly. This article reviews the endothelial response observed in sepsis and its effects on organ function, summarizes current progress in the development of therapeutic interventions targeting the endothelial response, and discusses future research directions to serve as a reference for researchers in the field.

Effect of endothelial responses on sepsis-associated organ dysfunction.

Sepsis is a severe systemic inflammatory syndrome characterized by a dysregulated immune response to infection, often leading to high mortality rates. The intestine, owing to its distinct structure and physiological environment, plays a pivotal role in the pathophysiology of sepsis. It functions as the "central organ" or "engine" in the progression of sepsis, with intestinal injury exacerbating the condition. Despite the availability of current therapies that offer partial symptom relief, they fall short of adequately protecting the intestinal barrier. In this study, an advanced nanodrug formulation (OLA@MΦ NPs) is developed by coating macrophage membranes onto polymeric organic nanoparticles encapsulating olaparib. When loaded into pH-responsive capsules, an intestine-decipher engineered capsule (cp-OLA@MΦ NPs) is successfully formulated. Upon oral administration in septic mice, these capsules withstand gastric acid and release their contents in the intestine, specifically targeting injured tissues. The released OLA@MΦ NPs effectively neutralize pro-inflammatory cytokines via macrophage membrane receptors, while olaparib inhibits intestinal epithelial parthanatos (a form of programmed cell death) by suppressing poly(ADP-ribose) polymerase 1 (PARP1) activation. This strategy significantly reduces bacterial translocation, slows the progression of sepsis, and enhances survival in septic mice, thus presenting a promising therapeutic approach for sepsis in clinical applications.

Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition.

Sepsis and their sequelae are the leading causes of death in intensive care units, with limited therapeutic options. Immunoparalysis plays a vital role in the pathophysiological progression of sepsis, leading to intracellular persistent infections and high mortality of septic patients. Eradicating intracellular infections and rescuing immunoparalysis are critical for sepsis management, yet effective tactics remain elusive. Here, we report immunomodulatory nanozymes (named PdIr@OMVs) that enable intracellular bacteria elimination and reinvigorate systemic innate-adaptive immune response during immunoparalysis to tackle multidrug-resistant (MDR) bacterial sepsis. The PdIr@OMVs are designed by encapsulating plasmonic PdIr nanocatalysts with immunostimulants of biocompatible bacterial outer membrane vesicles (OMVs). PdIr@OMVs exhibit unique localized surface plasmon response-enhanced peroxidase-like catalytic activity, and inherit the remarkable immunocyte-targeting capability and adjuvanticity of OMVs. We demonstrate that PdIr@OMVs not only potentiate the phagolysosomal killing effect of impaired macrophages via in situ catalysis to eradicate intracellular MDR bacteria and burst antigen release, but also allow rapid activation/maturation of dendritic cells to boost the presentation of bacterial antigen and orchestrate innate-adaptive immunity for rescuing immunoparalysis. In two immunocompromised mouse models of MDR bacterial sepsis, PdIr@OMVs collaboratively reduce bacterial burden and restore immune homeostasis, thereby circumventing organ damage and enabling the recovery of septic mice. Our work offers a promising therapeutic modality for sepsis and septic shock.

Immunomodulatory Nanozymes Eradicate Intracellular Infections and Rescue Immunoparalysis for Treating Multidrug-Resistant Bacterial Sepsis.

Sepsis-induced acute lung injury (ALI) is a life-threatening condition with limited therapeutic options, driven by a dysregulated inflammatory response within the pulmonary microenvironment. Although hyperactivation of poly (ADP-ribose) polymerase-1 (PARP-1) is recognized as a key contributor to inflammation and cellular injury, its cell type-specific roles in sepsis and strategies for targeted inhibition remain insufficiently explored. In this study, we first identified pulmonary epithelial cells and macrophages as major pro-inflammatory hubs in the septic lung using single-cell RNA sequencing. Based on these findings, we engineered a lung-targeted nanotherapeutic by encapsulating the PARP-1 inhibitor olaparib (OLA) into surfactant protein A (SPA)-functionalized microparticles (OLA@SPA MPs). The OLA@SPA MPs exhibited enhanced pulmonary accumulation and efficient internalization by target cells, resulting in robust suppression of PARP-1 activation. In murine models of sepsis, treatment with OLA@SPA MPs markedly reduced vascular leakage, modulated the cytokine storm, attenuated lung histopathological damage, and significantly improved survival. Mechanistically, transcriptomic analyses revealed that OLA@SPA MPs reversed sepsis-associated gene expression signatures, particularly by downregulating key pro-inflammatory pathways such as NOD-like receptor and tumor necrosis factor (TNF) signaling. Collectively, this work establishes a targeted therapeutic paradigm that translates mechanistic insights into an effective intervention for sepsis-induced lung injury.

Targeted inhibition of PARP-1 in pulmonary epithelial cells and macrophages via SPA-functionalized microparticles attenuates sepsis-induced lung injury.

Article	Year
The Role of Gut Microbiota in Tumor Immunotherapy. Journal of immunology research\| PubMed ID: 34485534	2021
Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice. Redox biology\| PubMed ID: 35981417	2022
Corrigendum to "Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice" [Redox Biol. 56 (2022) 102432]. Redox biology\| PubMed ID: 38233242	2024
Retraction notice to: Corrigendum to "Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice" [Redox Biol. 70 (2024) 103036]. Redox biology\| PubMed ID: 38824118	2024
Retraction notice to: Macrophage SAMSN1 protects against sepsis-induced acute lung injury in mice [Redox Biol. 56 (2022) 102432]. Redox biology\| PubMed ID: 38851952	2024
[Basic research in sepsis: advances and challenges]. Zhonghua wei zhong bing ji jiu yi xue\| PubMed ID: 38991952	2024
Effect of endothelial responses on sepsis-associated organ dysfunction. Chinese medical journal\| PubMed ID: 39501810	2024
Intestine-Decipher Engineered Capsules Protect Against Sepsis-induced Intestinal Injury via Broad-spectrum Anti-inflammation and Parthanatos Inhibition. Advanced science (Weinheim, Baden-Wurttemberg, Germany)\| PubMed ID: 39836501	2025
Immunomodulatory Nanozymes Eradicate Intracellular Infections and Rescue Immunoparalysis for Treating Multidrug-Resistant Bacterial Sepsis. Exploration (Beijing, China)\| PubMed ID: 41163807	2025
Targeted inhibition of PARP-1 in pulmonary epithelial cells and macrophages via SPA-functionalized microparticles attenuates sepsis-induced lung injury. Materials today. Bio\| PubMed ID: 41809387	2026

Chengtai Ma

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