From Molecular Mechanisms to Clinical Therapy: Understanding Sepsis-Induced Multiple Organ Dysfunction DOI Open Access
Tijana Srdić,

Siniša Đurašević,

Iva Lakić

и другие.

International Journal of Molecular Sciences, Год журнала: 2024, Номер 25(14), С. 7770 - 7770

Опубликована: Июль 16, 2024

Sepsis-induced multiple organ dysfunction arises from the highly complex pathophysiology encompassing interplay of inflammation, oxidative stress, endothelial dysfunction, mitochondrial damage, cellular energy failure, and dysbiosis. Over past decades, numerous studies have been dedicated to elucidating underlying molecular mechanisms sepsis in order develop effective treatments. Current research underscores liver cardiac along with acute lung kidney injuries, as predominant causes mortality patients. This understanding sepsis-induced failure unveils potential therapeutic targets for treatment. Various novel therapeutics, including melatonin, metformin, palmitoylethanolamide (PEA), certain herbal extracts, gut microbiota modulators, demonstrated efficacy different models. In recent years, focus has shifted anti-inflammatory antioxidative agents exploring modulation metabolism sepsis. These approaches shown a significant impact preventing damage various animal models but require further clinical investigation. The accumulation this knowledge enriches our is anticipated facilitate development strategies future.

Язык: Английский

Network pharmacology prediction and molecular docking-based strategy to explore the potential mechanism of Huanglian Jiedu Decoction against sepsis DOI
Li Xing,

Shizhang Wei,

Shengqi Niu

и другие.

Computers in Biology and Medicine, Год журнала: 2022, Номер 144, С. 105389 - 105389

Опубликована: Март 9, 2022

Язык: Английский

Процитировано

267
Cytokine Storm—Definition, Causes, and Implications DOI Open Access
Dominik Jarczak, Axel Nierhaus

International Journal of Molecular Sciences, Год журнала: 2022, Номер 23(19), С. 11740 - 11740

Опубликована: Окт. 3, 2022

The human innate and adaptive immune systems consist of effector cells producing cytokines (interleukins, interferons, chemokines, numerous other mediators). Usually, a fragile equilibrium pro- anti-inflammation effects is maintained by complex regulatory mechanisms. Disturbances this homeostasis can lead to intricate chain reactions resulting in massive release cytokines. This may result drastic self-reinforcement various feedback mechanisms, which ultimately systemic damage, multi-organ failure, or death. Not only pathogens initiate such disturbances, but also congenital diseases immunomodulatory therapies. Due the diverse interactions within systems, understanding important clinical syndrome incomplete date effective therapeutic approaches remain scarce.

Язык: Английский

Процитировано

151
miR-125b-5p in adipose derived stem cells exosome alleviates pulmonary microvascular endothelial cells ferroptosis via Keap1/Nrf2/GPX4 in sepsis lung injury DOI Creative Commons

Kuo Shen,

Xujie Wang, Yunwei Wang

и другие.

Redox Biology, Год журнала: 2023, Номер 62, С. 102655 - 102655

Опубликована: Март 9, 2023

Sepsis is a fatal disease with high rate of morbidity and mortality, during which acute lung injury the earliest most serious complication. Injury pulmonary microvascular endothelial cells (PMVECs) induced by excessive inflammation plays an important role in sepsis injury. This study meant to explore protective effect mechanism ADSCs exosomes on PMVECs injury.We successfully isolated exosomes, characteristic were confirmed. reduced inflammatory response ROS accumulation cell PMVECs. Besides, inhibited ferroptosis while upregulated expression GPX4 And further inhibition experiments revealed that alleviated via upregulating GPX4. Meanwhile, could increase nucleus translocation Nrf2, decrease Keap1. miRNA analysis verified specific delivery miR-125b-5p Keap1 ferroptosis. In CLP model, relieve tissue death rate. oxidative stress tissue, remarkably Nrf2 GPX4.Collectively, we illustrated novel potentially therapeutic alleviate regulating Keap1/Nrf2/GPX4 expression, hence improve sepsis.

Язык: Английский

Процитировано

145
Post-acute sequelae of COVID-19: understanding and addressing the burden of multisystem manifestations DOI Creative Commons
Matteo Parotto, Mariann Gyöngyösi, Kathryn L. Howe

и другие.

The Lancet Respiratory Medicine, Год журнала: 2023, Номер 11(8), С. 739 - 754

Опубликована: Июль 17, 2023

Individuals with SARS-CoV-2 infection can develop symptoms that persist well beyond the acute phase of COVID-19 or emerge after phase, lasting for weeks months initial illness. The post-acute sequelae COVID-19, which include physical, cognitive, and mental health impairments, are known collectively as long COVID post-COVID-19 condition. substantial burden this multisystem condition is felt at individual, health-care system, socioeconomic levels, on an unprecedented scale. Survivors COVID-19-related critical illness risk respiratory distress syndrome, sepsis, chronic illness, these multidimensional morbidities might be difficult to differentiate from specific effects COVID-19. We provide overview manifestations in adults. explore various organ systems, describe potential pathophysiological mechanisms, consider challenges providing clinical care support survivors manifestations. Research needed reduce incidence optimise therapeutic rehabilitative patients.

Язык: Английский

Процитировано

137
Neutrophils and emergency granulopoiesis drive immune suppression and an extreme response endotype during sepsis DOI Creative Commons
Andrew Kwok, Alice Allcock, Ricardo C. Ferreira

и другие.

Nature Immunology, Год журнала: 2023, Номер 24(5), С. 767 - 779

Опубликована: Апрель 24, 2023

Sepsis arises from diverse and incompletely understood dysregulated host response processes following infection that leads to life-threatening organ dysfunction. Here we showed neutrophils emergency granulopoiesis drove a maladaptive during sepsis. We generated whole-blood single-cell multiomic atlas (272,993 cells, n = 39 individuals) of the sepsis immune identified populations immunosuppressive mature immature neutrophils. In co-culture, CD66b+ inhibited proliferation activation CD4+ T cells. Single-cell mapping circulating hematopoietic stem progenitor cells (HSPCs) (29,366 27) indicated altered in patients with These features were enriched patient subset poor outcome specific signature displayed higher frequencies IL1R2+ neutrophils, epigenetic transcriptomic signatures HSPCs STAT3-mediated gene regulation across different infectious etiologies syndromes. Our findings offer potential therapeutic targets opportunities for stratified medicine severe infection.

Язык: Английский

Процитировано

135
Immunopathophysiology of human sepsis DOI Creative Commons
W. Joost Wiersinga, Tom van der Poll

EBioMedicine, Год журнала: 2022, Номер 86, С. 104363 - 104363

Опубликована: Дек. 1, 2022

Язык: Английский

Процитировано

122
The pathophysiology of sepsis and precision-medicine-based immunotherapy DOI
Evangelos J. Giamarellos‐Bourboulis, Anna C. Aschenbrenner, Michael Bauer

и другие.

Nature Immunology, Год журнала: 2024, Номер 25(1), С. 19 - 28

Опубликована: Янв. 1, 2024

Язык: Английский

Процитировано

103
Balance Cell Apoptosis and Pyroptosis of Caspase-3-Activating Chemotherapy for Better Antitumor Therapy DOI Open Access

Lingjiao Li,

Shengmei Wang,

Wenhu Zhou

и другие.

Cancers, Год журнала: 2022, Номер 15(1), С. 26 - 26

Опубликована: Дек. 21, 2022

Chemotherapy is a standard treatment modality in clinic that exerts an antitumor effect via the activation of caspase-3 pathway, inducing cell death. While number chemotherapeutic drugs have been developed to combat various types tumors, severe side effects their common limitation, due nonspecific drug biodistribution, bringing significant pain cancer patients. Recently, scientists found that, besides apoptosis, chemotherapy could also cause pyroptosis, both which great influence on therapeutic index. For example, apoptosis is, generally, regarded as main mechanism killing tumor cells, while pyroptosis tumors promotes efficacy, but normal tissue results toxicity. Therefore, research efforts paid exploring rational modulation mode death induced by chemotherapy. This critical review aims summarize recent progress field, focusing how balance and for better We first reviewed mechanisms chemotherapy-induced activated key signaling molecule regulating deaths. Then, we systematically discussed rationale methods switching enhanced well blockage decrease effects. To tissues, level GSDME expression tumor-targeting delivery are two important factors. Finally, proposed potential future directions, may provide guidance researchers field.

Язык: Английский

Процитировано

71
The signaling pathways and therapeutic potential of itaconate to alleviate inflammation and oxidative stress in inflammatory diseases DOI Creative Commons
Xuan Shi, Huanping Zhou, Juan Wei

и другие.

Redox Biology, Год журнала: 2022, Номер 58, С. 102553 - 102553

Опубликована: Ноя. 24, 2022

Endogenous small molecules are metabolic regulators of cell function. Itaconate is a key molecule that accumulates in cells when the Krebs cycle disrupted. derived from cis-aconitate decarboxylation by decarboxylase (ACOD1) mitochondrial matrix and also known as immune-responsive gene 1 (IRG1). Studies have demonstrated itaconate plays an important role regulating signal transduction posttranslational modification through its immunoregulatory activities. bridge among metabolism, inflammation, oxidative stress, immune response. This review summarizes structural characteristics classical pathways itaconate, derivatives, compounds release itaconate. Here, mechanisms action, including transcriptional regulation ATF3/IκBζ axis type I IFN, protein KEAP1, inflammasome, JAK1/STAT6 pathway, TET2, TFEB, succinate dehydrogenase glycolytic enzyme presented. Moreover, roles diseases related to inflammation stress induced autoimmune responses, viruses, sepsis IRI discussed this review. We hope information provided will help increase understanding cellular metabolism improve clinical treatment stress.

Язык: Английский

Процитировано

70
Dysbiosis of a microbiota–immune metasystem in critical illness is associated with nosocomial infections DOI Creative Commons
Jared Schlechte, Amanda Z. Zucoloto,

Ian-Ling Yu

и другие.

Nature Medicine, Год журнала: 2023, Номер 29(4), С. 1017 - 1027

Опубликована: Март 9, 2023

Critically ill patients in intensive care units experience profound alterations of their gut microbiota that have been linked to a high risk hospital-acquired (nosocomial) infections and adverse outcomes through unclear mechanisms. Abundant mouse limited human data suggest the can contribute maintenance systemic immune homeostasis, intestinal dysbiosis may lead defects defense against infections. Here we use integrated systems-level analyses fecal dynamics rectal swabs single-cell profiling inflammatory responses prospective longitudinal cohort study critically show immunity function as an metasystem, where is coupled impaired host increased frequency nosocomial Longitudinal analysis by 16s rRNA gene sequencing blood using mass cytometry revealed during acute critical illness were highly interconnected dominated Enterobacteriaceae enrichment, dysregulated myeloid cell amplified inflammation, with lesser impact on adaptive mechanisms defense. Intestinal enrichment was innate antimicrobial effector responses, including hypofunctional immature neutrophils associated various bacterial fungal pathogens. Collectively, our findings metasystem between response drive susceptibility illness.

Язык: Английский

Процитировано

60