Epigenetic dysregulation of autophagy in sepsis-induced acute kidney injury: the underlying mechanisms for renoprotection

Frontiers in Immunology, Год журнала: 2023, Номер 14

Опубликована: Май 5, 2023

Sepsis-induced acute kidney injury (SI-AKI), a common critically ill, represents one of the leading causes global death. Emerging evidence reveals autophagy as pivotal modulator SI-AKI. Autophagy affects cellular processes renal lesions, including cell death, inflammation, and immune responses. Herein, we conducted systematic comprehensive review on topic proposed roles in Forty-one relevant studies were finally included further summarized analyzed. This revealed that majority (24/41, 58.5%) showed an elevation level during SI-AKI, while 22% 19.5% reported inhibition at early stage but declination respectively. Multiple intracellular signaling molecules pathways targeting (e.g. mTOR, non-coding RNA, Sirtuins family, mitophagy, AMPK, ROS, NF-Kb, Parkin) involved process exerting multiple biological effects kidney. treatment modalities small molecule inhibitors, temsirolimus, rapamycin, polydatin, ascorbate, recombinant human erythropoietin, stem cells, Procyanidin B2, dexmedetomidine) have been found to improve function, which may be attributed Though exact SI-AKI not well elucidated, it implicated preventing through various molecular pathways. Targeting autophagy-associated proteins hint towards new prospective ill patients with more preclinical are still warranted validate this hypothesis.

Язык: Английский

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Positive pathogens in stool could predict the clinical outcomes of sepsis-associated acute kidney injury in critical ill patient

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Май 16, 2024

In this study, we sought to evaluate the influence of positive pathogens in stool (PPS) on clinical outcomes critical ill patients with Sepsis-associated acute kidney injury (S-AKI) from intensive care unit. Our sample consisted 7338 patients, whom 752 (10.25%) had PPS. We found that presence Clostridium difficile (C. difficile) and protists samples was correlated survival during hospitalization, as well 30-day 90-day survival. Interestingly, there no significant difference overall in-hospital between PPS group negative (NPS) control group. However, cumulative incidence infection-related mortality significantly higher (53 vs. 48%, P = 0.022), particularly C. their specimens. After adjusting for propensity scores, results also have statistical significance. These findings suggest may affect 90-days S-AKI, samples. Further research is warranted further explore these associations.

Язык: Английский

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Effects and mechanisms of frehmaglutin D and rehmaionoside C improve LPS-induced acute kidney injury through the estrogen receptor-mediated TLR4 pathway in vivo and in vitro

Phytomedicine, Год журнала: 2023, Номер 123, С. 155218 - 155218

Опубликована: Ноя. 14, 2023

Sepsis-induced acute kidney injury (S-AKI) is an inflammatory disease with sex differences and there has no effective drugs to cure it. Frehmaglutin D (Fre D) rehmaionoside C (Reh C) are two violetone compounds estrogenic activity isolated from Rehmannia glutinosa. However, whether these exert protective effects on S-AKI through their estrogen-like unclear. This study aimed explore the mechanisms of Fre Reh lipopolysaccharide (LPS)-induced estrogen receptor pathway in vivo vitro interaction between ER TLR4 for first time. The LPS-induced female BALB/c mice mouse model was established by adding antagonist ICI182,780. Renal function, inflammation, oxidative stress, apoptosis, immune cells, expression key proteins ER-TLR4-IL-1β were tested. affinity investigated molecular docking. Then, established, ERα/ERβ antagonists (MPP/PHTPP) added combined gene overexpression techniques. further explored Co-IP, GST pull-down SPR ameliorated renal damage, inflammation mice, regulated decreased ROS levels, increased ERα ERβ protein expression, TLR4, caspase 11 IL-1β expression. These blocked Molecular docking results showed that bound similar potency. suggested reduced levels 11, cells. All reversed addition MPP/PHTPP enhanced after significant difference effects. Moreover, indirect or direct binding concentration dependent. may improve act both receptors. interact directly indirectly which studied

Язык: Английский

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Nanoparticles constructed from natural polyphenols are used in acute kidney injury

Journal of Materials Chemistry B, Год журнала: 2024, Номер 12(36), С. 8883 - 8896

Опубликована: Янв. 1, 2024

Acute kidney injury (AKI) is a severe clinical syndrome characterized by rapid deterioration of renal function caused variety pathogeneses.

Язык: Английский

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A promising application of kidney-specific cell-free DNA methylation markers in real-time monitoring sepsis-induced acute kidney injury

Epigenetics, Год журнала: 2024, Номер 19(1)

Опубликована: Окт. 7, 2024

Sepsis-induced acute kidney injury (SI-AKI) is a common clinical syndrome that associated with high mortality and morbidity. Effective timely detection may improve the outcome of SI-AKI. Kidney-derived cell-free DNA (cfDNA) provide new insight into understanding identifying Plasma cfDNA from 82 healthy individuals, 7 patients sepsis non-acute (SN-AKI), 9 SI-AKI was subjected to genomic methylation sequencing. We deconstructed relative contribution different cell types based on cell-specific markers focused exploring association between kidney-derived SI-AKI.Based deconvolution methylome: displayed elevated concentrations an increased epithelial cells (kidney-Ep) DNA; kidney-Ep derived achieved accuracy in distinguishing SN-AKI (AUC = 0.92, 95% CI 0.7801-1); higher kidney-ep tended correlate more advanced stages SI-AKI; strikingly, potential damage unmet by criteria showed levels than individuals. The autonomous screening (

Язык: Английский

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The role of inflammatory response and metabolic reprogramming in sepsis-associated acute kidney injury: mechanistic insights and therapeutic potential

Frontiers in Immunology, Год журнала: 2024, Номер 15

Опубликована: Окт. 31, 2024

Sepsis represents a severe condition characterized by organ dysfunction resulting from dysregulated host response to infection. Among the organs affected, kidneys are particularly vulnerable, with significant functional impairment that markedly elevates mortality rates. Previous researches have highlighted both inflammatory dysregulation and metabolic reprogramming crucial in onset progression of sepsis associated acute kidney injury (SA-AKI), making these processes potential targets for innovative therapies. This study aims elucidate pathophysiological mechanisms renal perspective dysregulation, particular emphasis on pyroptosis, necroptosis, autophagy, ferroptosis. Furthermore, it will incorporate insights into provide detailed analysis driving SA-AKI explore targeted therapeutic strategies, providing solid theoretical framework development therapies SA-AKI.

Язык: Английский

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Nucleic acid-based nanotherapeutics for treating sepsis and associated organ injuries

Theranostics, Год журнала: 2024, Номер 14(11), С. 4411 - 4437

Опубликована: Янв. 1, 2024

In recent years, gene therapy has been made possible with the success of nucleic acid drugs against sepsis and its related organ dysfunction.Therapeutics based on acids such as small interfering RNAs (siRNAs), microRNAs (miRNAs), messenger (mRNAs), plasmid DNAs (pDNAs) guarantee to treat previously undruggable diseases.The advantage acid-based lies in development nanocarriers, achieving targeted controlled delivery for improved efficacy minimal adverse effects.Entrapment into nanocarriers also ameliorates poor cellular uptake naked acids.In this study, we discuss current state art nanoparticles hyperinflammation apoptosis associated sepsis.The optimized design through physicochemical property modification ligand conjugation can target specific organs-such lung, heart, kidney, liver-to mitigate multiple sepsis-associated injuries.This review highlights nanomaterials designed fabricating anti-sepsis nanosystems, their characterization, mechanisms working sepsis, potential promoting therapeutic efficiency acids.The investigations nanoparticulate application management are summarized paper.Noteworthily, nanotherapeutic allows a novel strategy sepsis.Further clinical studies required confirm findings cell-and animal-based experiments.The capability large-scale production reproducibility nanoparticle products critical commercialization.It is expected that numerous possibilities will be investigated nanotherapeutics future.

Язык: Английский

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Aspirin reduces the mortality risk of sepsis-associated acute kidney injury: an observational study using the MIMIC IV database

Frontiers in Pharmacology, Год журнала: 2023, Номер 14

Опубликована: Июль 25, 2023

Introduction: Sepsis-associated acute kidney injury (SA-AKI) is a complication of sepsis and characterized by high mortality. Aspirin affects cyclooxygenases which play significant role in inflammation, hemostasis, immunological regulation. Sepsis an uncontrolled inflammatory procoagulant response to pathogen, but aspirin can inhibit platelet function attenuate the response, thus improving outcomes. Several studies have generated contradictory evidence regarding effect on patients with sepsis-associated (SA-AKI). We conducted analysis MIMIC IV database investigate correlation between utilization outcomes SA-AKI, as well determine most effective dosage for therapy. Materials methods: SA-AKI patients' clinical data were extracted from MIMIC-IV2.1. Propensity score matching was applied balance baseline characteristics group non-user group. Subsequently, relationship patient death analyzed Kaplan-Meier method Cox proportional hazard regression models. Results: 12,091 database. In propensity score-matched sample 7,694 individuals, lower 90-day mortality risks observed compared non-users (adjusted HR: 0.722; 95%CI: 0.666, 0.783) multivariable cox hazards analysis. addition, survival curves indicated superior rate users (the log-rank test p-value 0.001). And median time receiving treatment significantly longer than those not (46.47 days vs. 24.26 days). group, average ICU stay length shorter (5.19 5.58 days, p = 0.006). There no association increased risk gastrointestinal hemorrhage (p 0.144). Conclusion: might reduce duration 30-day or patients. No statistically difference found control

Язык: Английский

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Reduction in NGAL at 48 h predicts the progression to CKD in patients with septic associated AKI: a single-center clinical study

International Urology and Nephrology, Год журнала: 2023, Номер 56(2), С. 607 - 613

Опубликована: Июнь 29, 2023

Язык: Английский

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Early fluid plus norepinephrine resuscitation diminishes kidney hypoperfusion and inflammation in septic newborn pigs

Shock, Год журнала: 2024, Номер unknown

Опубликована: Апрель 23, 2024

Sepsis is the most frequent risk factor for acute kidney injury (AKI) in critically ill infants. Sepsis-induced dysregulation of microcirculation newborns unresolved. The objective this study was to use translational swine model evaluate changes function during early phase sepsis and impact fluid plus norepinephrine resuscitation. Newborn pigs (3-7-day-old) were allocated randomly three groups: 1) sham, 2) (cecal ligation puncture) without subsequent resuscitation, 3) with lactated Ringer All animals underwent standard anesthesia mechanical ventilation. Cardiac output glomerular filtration rate measured noninvasively. Mean arterial pressure, total renal blood flow, cortical perfusion, medullary tissue oxygen tension (mtPO 2 ) determined 12 h. Cecal puncture decreased mean pressure cardiac by more than 50%, a proportional increase vascular resistance 60-80% reduction mtPO compared sham. also ~79% increased AKI biomarkers. Isolated foci tubular necrosis observed septic piglets. Except , all these parameters ameliorated resuscitated Resuscitation attenuated sepsis-induced increases levels plasma C-reactive protein, proinflammatory cytokines, lactate dehydrogenase, alanine transaminase, aspartate aminotransferase, NLRP3 inflammasome. These data suggest that newborn subjected cecal develop hypodynamic AKI. Early implementation resuscitation lessens degree inflammation, AKI, liver injury.

Язык: Английский

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