Abstract Due to the continuous evolution of SARS-CoV-2, the Omicron variant has emerged and exhibits severe immune evasion. The high number of mutations at key antigenic sites on the spike protein has made a large number of existing antibodies and vaccines ineffective against this variant. Therefore, it is urgent to develop efficient broad-spectrum neutralizing therapeutic drugs. Here we characterize a rabbit monoclonal antibody (RmAb) 1H1 with broad-spectrum neutralizing potency against Omicron sublineages including BA.1, BA.1.1, BA.2, BA.2.12.1, BA.2.75, BA.3 and BA.4/5. Cryo-electron microscopy (cryo-EM) structure determination of the BA.1 spike-1H1 Fab complexes shows that 1H1 targets a highly conserved region of RBD and avoids most of the circulating Omicron mutations, explaining its broad-spectrum neutralization potency. Our findings indicate 1H1 as a promising RmAb model for designing broad-spectrum neutralizing antibodies and shed light on the development of therapeutic agents as well as effective vaccines against newly emerging variants in the future.
Abstract Earthworms, long utilized in traditional medicine, serve as a source of inspiration for modern therapeutics. Lysenin, a defensive factor in the coelom fluid of the earthworm Eisenia fetida , has multiple bioactivities. However, the inherent toxicity of Lysenin as a pore‐forming protein (PFP) restricts its application in therapy. Here, a gene therapy strategy based on Lysenin for cancer treatment is presented. The formulation consists of polymeric nanoparticles complexed with the plasmid encoding Lysenin. After transfection in vitro, melanoma cells can express Lysenin, resulting in necrosis, autophagy, and immunogenic cell death. The secretory signal peptide alters the intracellular distribution of the expressed product of Lysenin , thereby potentiating its anticancer efficacy. The intratumor injection of Lysenin gene formulation can efficiently kill the transfected melanoma cells and activate the antitumor immune response. Notably, no obvious systemic toxicity is observed during the treatment. Non‐viral gene therapy based on Lysenin derived from Eisenia foetida exhibits potential in cancer therapy, which can inspire future cancer therapeutics.
Gut microbiota, a collection of microorganisms that live within gastrointestinal tract, provides crucial signaling metabolites for the physiological of hosts. In healthy state, gut microbiota metabolites are helpful for maintaining the basic functions of hosts, whereas disturbed production of these metabolites can lead to numerous diseases such as metabolic diseases, cardiovascular diseases, gastrointestinal diseases, neurodegenerative diseases, and cancer. Although there are many reviews about the specific mechanisms of gut microbiota metabolites on specific diseases, there is no comprehensive summarization of the functions of these metabolites. In this Opinion, we discuss the knowledge of gut microbiota metabolites including the types of gut microbiota metabolites and their ways acting on targets. In addition, we summarize their physiological and pathologic functions in health and diseases, such as shaping the composition of gut microbiota and acting as nutrition. This paper can be helpful for understanding the roles of gut microbiota metabolites and thus provide guidance for developing suitable therapeutic strategies to combat microbial-driven diseases and improve health.
Gut microbiota, a group of microorganisms that live in the gastrointestinal tract, plays important roles in health and disease. One mechanism that gut microbiota in modulation of the functions of hosts is achieved through synthesizing and releasing a series of metabolites such as short-chain fatty acids. In recent years, increasing evidence has indicated that dietary compounds can interact with gut microbiota. On one hand, dietary compounds can modulate the composition and function of gut microbiota; on the other hand, gut microbiota can metabolize the dietary compounds. Although there are several reviews on gut microbiota and diets, there is no focused review on the effects of dietary compounds on gut microbiota-derived metabolites. In this review, we first briefly discussed the types of gut microbiota metabolites, their origins, and the reasons that dietary compounds can interact with gut microbiota. Then, focusing on gut microbiota-derived compounds, we discussed the effects of dietary compounds on gut microbiota-derived compounds and the following effects on health. Furthermore, we give our perspectives on the research direction of the related research fields. Understanding the roles of dietary compounds on gut microbiota-derived metabolites will expand our knowledge of how diets affect the host health and disease, thus eventually enable the personalized diets and nutrients.
Objective
To investigate the dynamic changes in the nature of the pleural effusion via Light criteria in hypothermic rats induced by seawater immersion and analyze possible mechanism involved.
Methods
One hundred male Sprague-Dawley rats were randomly divided into the normal control group (without any treatment) and hypothermia group exposed to 20 ℃ seawater for 24 hours. Then, the hypothermia group was sub-divided into the passive rewarming groups 1, 2, 3 and 4 and warm water bath active rewarming groups 1, 2, 3 and 4, each consisting of 10 animals. The passive rewarming groups had passive rewarming after exposure to 20 ℃ seawater for 24 hours, while the active rewarming groups had warm water bath rewarming following exposure to 20 ℃ seawater for 24 hours. Then, all the animals in the sub-groups were executed 0, 3, 6 and 12 hours after rewarming. Serum, pleural effusion, total protein (TP) in pleural effusion, concentrations of lung homogenate lactate dehydrogenase (LDH) were measured, and Light criteria were calculated.
Results
There was no significant pleural effusion in the normal rats. LDH level in hypothermia-induced pleural effusion was higher than that in normal serum LDH, pleural effusion/total serum protein ratio (TPR) was lower than 0.5, and lactate dehydrogenase ratio (LDHR) was lower than 0.6. After rewarming, the amount of hypothermia-induced pleural effusion decreased gradually, while the levels of TPR and LDHR increased gradually. However, changes of LDH in pleural effusion were different with those in serum and lung homogenate. The warm water bath rewarming in the absorption of hypothermic pleural effusion was faster than passive rewarming, Warm water bath rewarming seemed to promote absorption of hypothermia-induced pleural effusion, but without statistical significance.
Conclusions
The 3 values of the pleural effusion criteria in hypothermic rats continuously increased following rewarming and reached the standards of effusion fluid, which did not necessarily reflect the seriousness of inflammatory pleural damage. The possible mechanism involved might be associated with the decrease of pleural effusion after rewarming, and water absorption by the body might be greater than protein absorption.
Key words:
Seawater immersion; Hypothermia; Rats; Rewarming; Pleural effusion; Light criteria
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