Editorial: Sepsis: Basic, Clinical and Therapeutic Approaches

Department of Critical Care Medicine, Institute of Critical Care Medicine, West China Hospital, Sichuan University, Chengdu, China, West China Tianfu Hospital, Sichuan Universities, Chengdu, China, Department of Surgery, UT Southwestern Medical Center, Dallas, TX, United States, Shanghai Institute of Materia Medica, Chinese Academy of Sciences, Pudong Zhangjiang HiTech Park, Shanghai, China, Key Laboratory of Basic Pharmacology of Ministry of Education and Joint International Research Laboratory of Ethnomedicine of Ministry of Education, Zunyi Medical University, Zunyi, China

(GLP-1RAs), a new drug in diabetes treatment, for the treatment of sepsis. They suggested that GLP-1RAs not only regulated blood glucose homeostasis but also improved organ dysfunction, regulated immunity, and controlled inflammation and other functions (such as renal function) in sepsis. Their study provides a new perspective treatment for sepsis patients with stress hyperglycemia.
Epigenetic regulation plays an important role in the pathogenesis of sepsis (Falcão-Holanda et al., 2021). The epigenetic changes in sepsis include DNA methylation, histone modifications, and regulation of transcription via non-coding RNAs (Zhang et al., 2019). The bromodomain and extra-terminal (BET) protein family, an epigenetic regulator of gene transcription, has recently been recognized as a significant regulator of inflammation and immune response in sepsis. Wang et al. opined that BETs not only function as scaffolds to recruit different transcription factors and transcription elongation complexes, but also serve as switches to initiate gene transcription machinery in response to the interaction of BDs with acetylated chromatin either at gene promoters or in long-range cis regulatory elements. This mini-review summarizes the emerging roles and applications of BETs in sepsis.
Since 2019, the COVID-19 pandemic has been a threat to public health and killed millions of people worldwide . In the early days of COVID-19, anti-pro-inflammatory cytokine antibodies were considered a promising treatment based on the observation that the over-release of pro-inflammatory cytokines was the cause of cytokine storms during COVID-19 (Schultze and Aschenbrenner, 2021). Accordingly, the systematic review by Wang et al. showed that the anti-cytokine antibodies tocilizumab, sarilumab, and anakinra could reduce mortality in patients with COVID-19; in particular, tocilizumab was not significantly associated with any serious adverse events or secondary infections. Further, Yuan et al. have also reviewed the potential of immune-related therapy in COVID-19 treatment and shed light on the current status of and advances in immune-related therapy for COVID-19 worldwide. In contrast to the promising effect of anti-cytokine therapy in COVID-19 treatment, in sepsis treatment, many clinical studies have found that antibodies have no therapeutic effect and may even increase mortality . Thus, the use of anti-cytokine antibodies in the treatment of sepsis is controversial.
Treating sepsis with a combination of vitamins (such as vitamin C and vitamin D) and probiotics is currently an area of great interest. Kamel et al. demonstrated that both combinations of interventions, vitamin C plus vitamin B1 and vitamin D plus oral Lactobacillus probiotics, improved APACHE II scores and reduced sepsis incidence in trauma patients. Further, in their randomized, double-blinded, controlled clinical trial, severe trauma patients were stratified by leukocyte anti-sedimentation rate (LAR) into high-risk and low-risk groups for sepsis, and LAR combined with injury severity score was found to be a good predictor of sepsis.
In summary, the articles described here report on novel targets in immunotherapy and new therapeutic approaches in sepsis treatment. However, more research is required on new drug targets based on the pathophysiological mechanism of sepsis and re-evaluation of the data on existing drugs in clinical trials.

AUTHOR CONTRIBUTIONS
HZ, YK, DT, and LL drafted the manuscript. HZ, YK, DT, and LL revised, edited, and provided their final approval. All authors listed contributed to the work and approved it for publication.