Absorption​ of free radicals in the body cannot be done by antioxidant compounds originating from the human body, so exogenous antioxidants are required to help in their natural antioxidant action. Oxidative stress can be caused by an imbalance of free radical inhibitors and the accumulation of free radicals that enter cellular structures. Synthetic antioxidants found in external antioxidants are not the primary choice because they are harmful and carcinogenic. Therefore, using natural ingredients provides a necessary alternative to constructing novel natural antioxidants. Recent studies have highlighted critical analysis and evaluation that flavonoids are a unique class of secondary metabolites found in plants and used in communities as traditional therapeutics with proven bioactivity. This could support new discoveries based on various herbal medicines and in addition, the functional effectiveness of flavonoids as antioxidants against free radicals. In this review, there are several strengths in the discussion. First, the study takes a comprehensive approach by covering various aspects, including the properties and sources of free radicals, oxidative stress in relation to different diseases, antioxidant defense mechanisms, and the specific antioxidant mechanisms of flavonoids. Second, the focus on natural antioxidants, especially flavonoids, and also discussion about clinical applications and human studies, limitations, global perspectives, and future research directions of flavonoids compounds become references in the selection of natural medicines. But, several constraints should be considered when interpreting the findings of this review. First, the discussion about the mechanism of antioxidant compounds is only discussed in general and only takes one example of a compound (flavonoid) that has the potential as an antioxidant. Second, the lack of findings regarding the relationship between several diseases discussed with free radicals. Third, a limited number of studies investigated regarding clinical applications and human studies of some of the diseases discussed. 

A Comprehensive Review of Free Radicals, Oxidative Stress, and Antioxidants: Overview, Clinical Applications, Global Perspectives, Future Directions, and Mechanisms of Antioxidant Activity of Flavonoid Compounds

Pneumonia is one of the major causes of death after pathogens infection. Zingiberis rhizoma (GAN JIANG) is a herb that used in combination with other Chinese medicines to treat pathogen such as virus induced pneumonia. However, the affect of hexahydrocurcumin (HHC), a component from Zingiberis rhizoma, on pneumonia remains unknown. This study aims to explore the effects of HHC on lipopolysaccharide (LPS)-induced acute pneumonia, and to clarify the underlying mechanism. The pneumonia model of C57BL/6 mice was established by intratracheal injection of LPS to evaluate the therapeutic effect of HHC on lung injury and inflammation in vivo. RAW264.7 macrophages were utilized to illustrate the cellular mechanism of HHC in vitro. HHC alleviated lung injury, ROS and inflammatory cytokine IL-6 production in pneumonia mice in vivo. Molecular docking results disclosed the binding of HHC to JAK1 protein. The study further showed that HHC suppressed the inflammatory cytokines such as IL-6, TNF-α, IL-1β gene expression, inhibited the phosphorylation of JAK1 but not JAK3, and the subsequent STAT3 phosphorylation in LPS-activated macrophages. HHC exhibited no effects on the protein levels of JAK1 and STAT3 in vitro. Consistently, HHC also attenuated the JAK1, STAT3 phosphorylation in pneumonia mice in vivo. The results reveal that HHC attenuates pneumonia by targeted inhibition of JAK1/STAT3 signaling pathway. It indicates the novel role of HHC to treat pneumonia, and its potential applications for JAK inhibitor-treated diseases. 

Hexahydrocurcumin from Zingiberis rhizoma attenuates lipopolysaccharide-induced acute pneumonia through JAK1/STAT3 signaling pathway.

Porcine epidemic diarrhea virus (PEDV) is the etiology of porcine epidemic diarrhea (PED), a highly contagious digestive disease in pigs and especially in neonatal piglets, in which a mortality rate of up to 100% will be induced. Immunizing pregnant sows remains the most promising and effective strategy for protecting their neonatal offspring from PEDV. Although half a century has passed since its first report in Europe and several prophylactic vaccines (inactivated or live attenuated) have been developed, PED still poses a significant economic concern to the swine industry worldwide. Hence, there is an urgent need for novel vaccines in clinical practice, especially live attenuated vaccines (LAVs) that can induce a strong protective lactogenic immune response in pregnant sows. Reverse genetic techniques provide a robust tool for virological research from the function of viral proteins to the generation of rationally designed vaccines. In this review, after systematically summarizing the research progress on virulence-related viral proteins, we reviewed reverse genetics techniques for PEDV and their application in the development of PED LAVs. Then, we probed into the potential methods for generating safe, effective, and genetically stable PED LAV candidates, aiming to provide new ideas for the rational design of PED LAVs.

Developing Next-Generation Live Attenuated Vaccines for Porcine Epidemic Diarrhea Using Reverse Genetic Techniques

Population genetics of horticultural crops aided by multi-omics technology and its implications for ornamental plants

Comprehensive analysis of the SmPIN gene family in Salix matsudana: roles in growth, development, and stress adaptation


 Crape myrtle (Lagerstroemia indica) is a globally used ornamental woody plant and is the representative species of Lagerstroemia. However, studies on the evolution and genomic breeding of L. indica were hindered by the lack of a reference genome. Here, we assembled the first high-quality genome of L. indica using PacBio combined with Hi-C scaffolding to anchor the 329.14 Mb genome assembly into 24 pseudochromosomes. We detected a previously undescribed independent WGT event occurring 35.5 MYA in L. indica following its divergence from P. granatum. After resequencing 73 accessions of Lagerstroemia, the main parents of modern crape myrtle cultivars were found to be L. indica and L. fauriei. During the process of domestication, genetic diversity tended to decrease in many plants, but this was not observed in L. indica. We constructed a high-density genetic linkage map with an average map distance of 0.33 cM. Furthermore, we synthesized the results of QTL mapping using genetic mapping and BSA localized the main-effect interval determining internode length (IL) to chr1, which contains CDL15, CRG98, and GID1b1 associated with the phytohormone pathways. Analysis of gene expression of the red, purple and white flower colour flavonoid pathways revealed that differential expression of multiple genes determined the flower colour of L. indica, with white flowers having the lowest gene expression. In addition, BSA of purple- and green-leaved individuals of populations of L. indica was performed, and the leaf colour loci were mapped to chr12 and chr17. Within these intervals, we identified MYB35, NCED, and KAS1. Our genome assembly provided a foundation for investigating the evolution, population structure and differentiation of Myrtaceae species and accelerated the molecular breeding of L. indica.

Genome assembly and resequencing analyses provide new insights into the evolution and ornamental traits of crape myrtle

Zoonotic coronaviruses infect mammals and birds, causing pulmonary and gastrointestinal infections. Some animal coronaviruses, such as the porcine epidemic diarrhea virus (PEDV) and transmissible gastroenteritis virus (TGEV), lead to severe diarrhea and animal deaths. Gastrointestinal symptoms were also found in COVID-19 and SARS patients. However, the pathogenesis of gastrointestinal symptoms in coronavirus diseases remains elusive. In this study, the main protease-induced LPCAT3 cleavage was monitored by exogenous gene expression and protease inhibitors, and the related regulation of gene expression was confirmed by qRT-PCR and gene knockdown. Interestingly, LPCAT3 plays an important role in lipid absorption in the intestines. The Mpro of coronaviruses causing diarrhea, such as PEDV and MERS-CoV, but not the Mpro of HCoV-OC43 and HCoV-HKU1, which could induce LPCAT3 cleavage. Mutagenesis analysis and inhibitor experiments indicated that LPCAT3 cleavage was independent of the catalytic activity of Mpro. Moreover, LPCAT3 cleavage in cells boosted CHOP and GRP78 expression, which were biomarkers of ER stress. Since LPCAT3 is critical for lipid absorption in the intestines and malabsorption may lead to diarrhea in coronavirus diseases, Mpro-induced LPCAT3 cleavage might trigger gastrointestinal symptoms during coronavirus infection. 

Coronaviral Main Protease Induces LPCAT3 Cleavage and Endoplasmic Reticulum (ER) Stress

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Genome assembly and resequencing analyses provide new insights into the evolution and ornamental traits of crape myrtle

Coronaviral Main Protease Induces LPCAT3 Cleavage and Endoplasmic Reticulum (ER) Stress