Sepsis is defined as “a life-threatening organ dysfunction caused by a host’s dysfunctional response to infection”. Although the treatment of sepsis has developed rapidly in the past few years, sepsis incidence and mortality in clinical treatment is still climbing. Moreover, because of the diverse manifestations of sepsis, clinicians continue to face severe challenges in the diagnosis, treatment, and management of patients with sepsis. Here, we review the recent development in our understanding regarding the cellular pathogenesis and the target of clinical diagnosis of sepsis, with the goal of enhancing the current understanding of sepsis. The present state of research on targeted therapeutic drugs is also elaborated upon to provide information for the treatment of sepsis.

The marine environment is an enormous source of marine-derived natural products (MNPs), and future investigation into anticancer drug discovery. Current progress in anticancer drugs offers a rise in isolation and clinical validation of numerous innovative developments and advances in anticancer therapy. However, only a limited number of FDA-approved marine-derived anticancer drugs are available due to several challenges and limitations highlighted here. The use of chitosan in developing marine-derived drugs is promising in the nanotech sector projected for a prolific anticancer drug delivery system (DDS). The cGAS-STING-mediated immune signaling pathway is crucial, which has not been significantly investigated in anticancer therapy and needs further attention. Additionally, a small range of anticancer mediators is currently involved in regulating various JAK/STAT signaling pathways, such as immunity, cell death, and tumor formation. This review addressed critical features associated with MNPs, origin, and development of anticancer drugs. Moreover, recent advances in the nanotech delivery of anticancer drugs and understanding into cancer immunity are detailed for improved human health.

Diabetes mellitus is a chronic multifaceted disease with multiple potential complications, the treatment of which can only delay and prolong the terminal stage of the disease, i.e., type 2 diabetes mellitus (T2DM). The World Health Organization predicts that diabetes will be the seventh leading cause of death by 2030. Although many antidiabetic medicines have been successfully developed in recent years, such as GLP-1 receptor agonists and SGLT-2 inhibitors, single-target drugs are gradually failing to meet the therapeutic requirements owing to the individual variability, diversity of pathogenesis, and organismal resistance. Therefore, there remains a need to investigate the pathogenesis of T2DM in more depth, identify multiple therapeutic targets, and provide improved glycemic control solutions. This review presents an overview of the mechanisms of action and the development of the latest therapeutic agents targeting T2DM in recent years. It also discusses emerging target-based therapies and new potential therapeutic targets that have emerged within the last three years. The aim of our review is to provide a theoretical basis for further advancement in targeted therapies for T2DM.

Background: Fucoxanthin (FX), a xanthophyll pigment which occurs in marine brown algae with remarkable biological properties, has been proven to be safe for consumption by animals. Although FX has various pharmacological effects including anti-inflammatory, anti-tumor, anti-obesity, antioxidant, anti-diabetic, anti-malarial, and anti-lipid, in vivo protective effect against sepsis has not been reported. In this study, we aimed at evaluation the efficacy of the FX in a model of sepsis mouse. Methods: FX was successfully isolated from Conticribra weissflogii ND-8 for the first time. The FX was identified by thin-layer chromatography (TLC), high-performance liquid chromatography-mass spectrometry (HPLC-MS), and nuclear magnetic resonance (NMR). Animals were randomly divided into 9 groups, including Sham group (mouse received an intraperitoneal injection of normal saline 1.0 ml/kg), FX-treated (0.1–1.0 ml/kg), Lipopolysaccharide (LPS)-treated (20 mg/kg), FX+LPS-treated (0.1–10.0 mg/kg and 20 mg/kg, respectively), and urinastatin groups (10⁴ U/kg). Nuclear factor (NF)-κB activation could be potential treatment for sepsis. NF-κB signaling components were determined by western-blotting. IL-6, IL-1β, TNF-α production, and NF-κB activation were evaluated by ELISA and immunofluorescent staining in vitro. Results: FX was found to decrease the expression of inflammatory cytokines including IL-6, IL-1β, and TNF-α, in a prophylactic manner in the LPS-induced sepsis mouse model. Meanwhile, FX significantly inhibits phosphorylation of the NF-κB signaling pathway induced by LPS at the cellular level and reduces the nuclear translocation of NF-κB. The IC₅₀ for suppressing the expression of NF-κB was 11.08 ± 0.78 μM in the THP1-Lucia™ NF-κB cells. Furthermore, FX also inhibits the expression of inflammatory factors in a dose-dependent manner with the IC₅₀ inhibition of IL-6 production was 2.19 ± 0.70 μM in Raw267.4 macrophage cells. It is likely that the molecules with the ability of targeting NF-κB activation and inflammasome assembly, such as fucoxanthin, are interesting subjects to be used for treating sepsis.

As a popular traditional fermented beverage, kombucha has been extensively studied for its health benefits. However, the science behind the anti-inflammatory effect of kombucha has not been well studied, and there is an urgent need to uncover the secrets of the anti-inflammatory properties of kombucha. Here, we investigate kombucha's protective effects against lipopolysaccharide (LPS)-induced sepsis and on the intestinal microecology in mice. The contents of reducing sugars, polyphenols, catechins, and organic acids in the kombucha group were identified using various methods. The results showed that the concentrations of acetic acid, gluconic acid, polyphenol, and glucuronic acid in the kombucha group were 55.70 ± 2.57 g L⁻¹, 50.20 ± 1.92 g L⁻¹, 2.36 ± 0.31, and 1.39 ± 0.22 g L⁻¹, respectively. The result also demonstrated that kombucha effectively improves the survival rate from 0% to 40%, and increases the thermoregulation in LPS-treated mice, which showed decreased mobility and had lost their appetite for food. Furthermore, kombucha reduced the levels of tumor necrosis factor-α and interleukins (IL)-1β and IL-6, restored the levels of T cells and macrophages in LPS-challenged mice, alleviated the histopathological damage, and inhibited NF-κB signaling in mice with LPS-induced sepsis. We demonstrated that kombucha effectively prevents cellular immune function disorder in mice at the initial stage of sepsis and exerts an immunomodulatory effect. In addition, the effect of kombucha on the gut microbiota was investigated during sepsis. Kombucha supplementation altered the diversity of the gut microbiota and promoted the growth of butyrate-producing bacteria, which exert anti-inflammatory effects. Our results illustrate the potential of kombucha as a novel anti-inflammatory agent against the development of systemic inflammatory responses associated with sepsis.

Huperzine A (HupA), a naturally occurring alkaloid in the plant family Huperziaceae, has drawn great interest for its potential application in Alzheimer disease therapy. Our primary objective was to identify alkaloid- and HupA-producing fungi from the Chinese folk herb, Huperzia serrata. We established a rapid and efficient model for screening HupA-producing endophytic fungal strains. The presence of HupA in Paecilomyces tenuis YS-13 was analysed by thin-layer chromatography, high-performance liquid chromatography and mass spectrometry. The fermentation yield of HupA was 21.0 μg/L, and the IC₅₀ of the crude extract of YS-13 fermentation broth was 1.27 ± 0.04 mg/mL. This is the first report of P. tenuis as a HupA-producing endophyte isolated from Huperziaceae.