Macrophages-regulating nanomedicines for sepsis therapy

Deng, Jiali; Wang, Rui; Huang, Shu Pin; Ding, Jinsong; Zhou, Wenhu

doi:10.1016/j.cclet.2022.06.011

Cited by 14 publications

(6 citation statements)

References 135 publications

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“…Moreover, as the major mechanism defending against viral infection, including SARS‐CoV‐2 infection, 46 the condition of immunity, especial adaptive immunity is strongly correlated with the vulnerability, severity, survival and the possibility of multiple infections. 47 , 48 , 49 Therefore, although the major target of SARS‐CoV‐2 infection is lung, 50 , 51 , 52 and multi‐organ damages had been reported upon infection, 53 , 54 evaluating long‐term adaptive immune system changes in convalescent COVID‐19 patients remains of great significance. In our study, TCR/BCR immune repertoire profiling reveals the residual alterations in the adaptive immune system of convalescent patients recovering from COVID‐19 6 months after infection, including lymphopenia, reduced diversity, skewed V/J gene usage and B cell repertoire activation.…”

Section: Discussionmentioning

confidence: 99%

Post‐hospitalization rehabilitation alleviates long‐term immune repertoire alteration in COVID‐19 convalescent patients

et al. 2023

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The global pandemic of Coronavirus disease 2019 (COVID‐19) caused by severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) is an once‐in‐a‐lifetime public health crisis. Among hundreds of millions of people who have contracted with or are being infected with COVID‐19, the question of whether COVID‐19 infection may cause long‐term health concern, even being completely recovered from the disease clinically, especially immune system damage, needs to be addressed. Here, we performed seven‐chain adaptome immune repertoire analyses on convalescent COVID‐19 patients who have been discharged from hospitals for at least 6 months. Surprisingly, we discovered lymphopenia, reduced number of unique CDR3s, and reduced diversity of the TCR/BCR immune repertoire in convalescent COVID‐19 patients. In addition, the BCR repertoire appears to be activated, which is consistent with the protective antibody titres, but serological experiments reveal significantly lower IL‐4 and IL‐7 levels in convalescent patients compared to those in healthy controls. Finally, in comparison with convalescent patients who did not receive post‐hospitalization rehabilitation, the convalescent patients who received post‐hospitalization rehabilitation had attenuated immune repertoire abnormality, almost back to the level of healthy control, despite no detectable clinic demographic difference. Overall, we report the potential long‐term immunological impairment for COVID‐19 infection, and correction of this impairment via post‐hospitalization rehabilitation may offer a new prospect for COVID‐19 recovery strategy.

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Section: Discussionmentioning

confidence: 99%

Post‐hospitalization rehabilitation alleviates long‐term immune repertoire alteration in COVID‐19 convalescent patients

et al. 2023

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“…Further data solidified the understanding of COVID-19 as a multiorgan disorder, capable of triggering complications even as patients endure persistent, cyclical symptoms (Deng et al, 2023). This debilitating, can manifest irrespective of initial illness severity and has been termed "Post-COVID-19 Syndrome" (PCS) or "Long COVID."…”

Section: Introductionmentioning

confidence: 90%

Inflammatory Modulation of Interleukin-17 and -23 in Long COVID Diabetic Patients

2024

J Angiotherapy

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Background: The global COVID-19 pandemic has brought forth a persistent challenge in the form of Post-COVID-19 Syndrome (PCS) or Long COVID, affecting approximately 1 in 10 cases. Among the various risk factors, diabetes has emerged as a significant predictor of severe outcomes, with hyperglycemia and hyperinflammation playing pivotal roles. Despite the known association, the exact mechanisms linking diabetes to Long COVID remain elusive, prompting the need for further investigation. This study aimed to explore the relationship between immune responses, particularly interleukin-17 and -23 levels, and Long COVID severity in diabetic individuals. Method: Fifty diabetic patients with Long COVID were compared with fifty diabetic controls. Blood cytokine levels were measured, and Long COVID severity was assessed using the Long COVID Severity Scale (PCS-SS). Results: Results revealed elevated levels of interleukin-17 and -23 in diabetic patients with Long COVID compared to those without the condition. Additionally, participants with Long COVID and diabetes reported significantly higher symptom severity across physical, psychological, and cognitive domains, as indicated by the Long COVID Severity Scale. Conclusion: These findings underscore a strong association between heightened inflammatory responses and increased Long COVID severity in diabetic individuals. Understanding these mechanisms could inform targeted interventions to improve outcomes for this vulnerable population, highlighting the importance of tailored management strategies for Long COVID in diabetics.

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“…About 1/5 of deaths worldwide are due to sepsis, which is typically brought on by bacterial infection along with systemic inflammatory reactions. − The gold standard of sepsis therapy has historically been prompt antibiotic administration. , The accumulation of reactive oxygen species (ROS) has widely been known as another important factor for sepsis treatment failure during the past decades. , This is because the bacteria and toxin would cause cells such as macrophages and endothelial cells, etc. to produce ROS, which might damage cellular protein and lipids, as well as result in cell death and the release of inflammatory cytokines. − Hence, sepsis therapy efficacy when antibiotics are simply administered has been limited thus far. , PMB is a cationic antimicrobial peptide and is effective against the majority of Gram-negative bacteria because it damages the bacterial membrane, − which endows it with low bacterial resistance. However, its further clinical application was also restrained due to its potential side effects like kidney toxicity and limited ROS scavenging ability, which calls for a strategy toward more efficient and safer PMB administration leveraging on material design.…”

Section: Introductionmentioning

confidence: 99%

Robust and Multifunctional Therapeutic Nanoparticles against Peritonitis-Induced Sepsis

Cao,

Zhang,

Yang

et al. 2024

Biomacromolecules

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Apart from bacterial growth and endotoxin generation, the excessive production of reactive radicals linked with sepsis also has a substantial impact on triggering an inflammatory response and further treatment failure. Hence, the rational design and fabrication of robust and multifunctional nanoparticles (NPs) present a viable means of overcoming this dilemma. In this study, we used antibiotic polymyxin B (PMB) and antioxidant natural polyphenolic protocatechualdehyde (PCA) to construct robust and multifunctional NPs for sepsis treatment, leveraging the rich chemistries of PCA. The PMB release profile from the NPs demonstrated pH-responsive behavior, which allowed the NPs to exhibit effective bacterial killing and radical scavenging properties. Data from in vitro cells stimulated with H 2 O 2 and lipopolysaccharide (LPS) showed the multifunctionalities of NPs, including intracellular reactive oxygen species (ROS) scavenging, elimination of the bacterial toxin LPS, inhibiting macrophage M1 polarization, and anti-inflammation capabilities. Additionally, in vivo studies further demonstrated that NPs could increase the effectiveness of sepsis treatment by lowering the bacterial survival ratio, the expression of the oxidative marker malondialdehyde (MDA), and the expression of inflammatory cytokine TNF-α. Overall, this work provides ideas of using those robust and multifunctional therapeutic NPs toward enhanced sepsis therapy efficiency.

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Macrophages-regulating nanomedicines for sepsis therapy

Cited by 14 publications

References 135 publications

Post‐hospitalization rehabilitation alleviates long‐term immune repertoire alteration in COVID‐19 convalescent patients

Post‐hospitalization rehabilitation alleviates long‐term immune repertoire alteration in COVID‐19 convalescent patients

Inflammatory Modulation of Interleukin-17 and -23 in Long COVID Diabetic Patients

Robust and Multifunctional Therapeutic Nanoparticles against Peritonitis-Induced Sepsis

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