Effect of Peroxiredoxin 1 on the biological function of airway epithelial cells and epithelial-mesenchymal transition

Peroxiredoxin 1(PRDX1)participates in tumor cell proliferation,apoptosis,migration,invasion,and the epithelial-to-mesenchymal transition(EMT).This study aimed to investigate the effect of PRDX1 on the EMT of airway epithelial cells stimulated with lipopolysaccharide(LPS)and transforming growth factor-beta 1(TGF-β1).PRDX1 overexpression significantly increased the proliferation and migration of human bronchial epithelial(BEAS-2B)cells,reduced cell apoptosis(p<0.01),and induced EMT and collagen deposition by upregulating the expression of the matrix metallopeptidase(MMP)2,MMP9,α-smooth muscle actin(α-SMA),N-cadherin,vimentin and twist proteins and inhibiting E-cadherin expression(p<0.05).PRDX1 overexpression promoted TGF-β1-mediated inhibition of cell proliferation and migration and significantly enhanced the TGF-β1-induced EMT and collagen synthesis(p<0.05).Knockdown of PRDX1 inhibited cell proliferation,migration,EMT,and collagen synthesis(p<0.01),reversed LPS-mediated inhibition of cell proliferation and migration,and significantly suppressed LPS-induced EMT and collagen synthesis(p<0.01).The result indicating that PRDX1 may be involved in LPS/TGF-1-induced EMT and collagen synthesis in human bronchial epithelial cells.

A comprehensive analysis of the Bencao(herbal)small RNA Atlas reveals novel RNA therapeutics for treating human diseases

Cross-kingdom herbal mi RNA was first reported in 2012.Using a modified herbal extraction protocol,we obtained 73,677,287sequences by RNA-seq from 245 traditional Chinese Medicine(TCM),of which 20,758,257 were unique sequences.We constructed a Bencao(herbal)small RNA(s RNA)Atlas(http://bencao.bmicc.cn),annotated the sequences by sequence-based clustering,and created a nomenclature system for Bencao s RNAs.The profiles of 21,757 mi RNAs in the Atlas were highly consistent with those of plant mi RNAs in mi RBase.Using software tools,our results demonstrated that all human genes might be regulated by s RNAs from the Bencao s RNA Atlas,part of the predicted human target genes were experimentally validated,suggesting that Bencao s RNAs might be one of the main bioactive components of herbal medicines.We established roadmaps for oligonucleotide drugs development and optimization of TCM prescriptions.Moreover,the decoctosome,a lipo-nano particle consisting of 0.5%–2.5%of the decoction,demonstrated potent medical effects.We propose a Bencao(herbal)Index,including small-molecule compounds(SM),protein peptides(P),nucleic acid(N),non-nucleic and non-proteinogenic large-molecule compounds(LM)and elements from Mendeleev's periodic table(E),to quantitatively measure the medical effects of botanic medicine.The Bencao s RNA Atlas is a resource for developing gene-targeting oligonucleotide drugs and optimizing botanical medicine,and may provide potential remedies for the theory and practice of one medicine.

Orally administered BZL-s RNA-20 oligonucleotide targeting TLR4 effectively ameliorates acute lung injury in mice

The global COVID-19 pandemic emerged at the end of December 2019.Acute respiratory distress syndrome(ARDS)and acute lung injury(ALI)are common lethal outcomes of bacterial lipopolysaccharide(LPS),avian influenza virus,and SARS-Co V-2.Toll-like receptor 4(TLR4)is a key target in the pathological pathway of ARDS and ALI.Previous studies have reported that herbal small RNAs(s RNAs)are a functional medical component.BZL-s RNA-20(Accession number:B59471456;Family ID:F2201.Q001979.B11)is a potent inhibitor of Toll-like receptor 4(TLR4)and pro-inflammatory cytokines.Furthermore,BZLs RNA-20 reduces intracellular levels of cytokines induced by lipoteichoic acid(LTA)and polyinosinic-polycytidylic acid(poly(I:C)).We found that BZL-s RNA-20 rescued the viability of cells infected with avian influenza H5N1,SARS-Co V-2,and several of its variants of concern(VOCs).Acute lung injury induced by LPS and SARS-Co V-2 in mice was significantly ameliorated by the oral medical decoctosome mimic(bencaosome;sphinganine(d22:0)+BZL-s RNA-20).Our findings suggest that BZLs RNA-20 could be a pan-anti-ARDS/ALI drug.

Analysis of non-coding small RNA similarity/sharing between plant and animal genomes

Dear Editor,During the construction and analysis of the Bencao(herbal)small RNA(s RNA)Atlas,the fact that many s RNAs from the human genome are present in the Bencao(herbal)database attracted our attention(Cao et al.,2023).The Bencao Atlas contains millions of s RNAs from hundreds of plants used in traditional Chinese Medicines(TCMs).

Herbal small RNAs in patients with COVID-19 linked to reduced DEG expression

In China,more than 80%of patients with coronavirus disease 2019(COVID-19)received traditional Chinese medicine(TCM)as a treatment and their clinical efficacy have been reported.However,the underlying molecular mechanism remains unclear.Previous studies have identified herbal small RNAs(s RNAs)as novel functional components.In this study,a cohort of 22patients with COVID-19 treated with Toujie Quwen(TQ)granules was analyzed.We observed thousands of herbal small RNAs that entered the blood cells of patients after the consumption of TQ granules.In response to this treatment,the reduced differentially expressed genes(DEGs)were highly correlated with the predicted target genes of the most prevalent herbal s RNAs detected in the blood.Moreover,the predicted target genes of the top 30 s RNAs from each of the 245 TCMs in the Bencao s RNA Atlas overlapped with 337 upregulated DEGs in patients with mild COVID-19,and 33 TCMs,with more than 50%overlapping genes were identified as effective TCMs.These predicted target genes of top 30 s RNAs from Juhong,Gualoupi and Foshou were confirmed experimentally.Our results not only elucidated a novel molecular mechanism of TCM potential clinical efficacy for COVID-19 patients,but also provided 33 effective COVID-19 TCMs for prescription optimization.

Potential oligonucleotide drugs in Bencao sRNA Atlas

Dear Editor,We read the Letter of Professor Shanfa Lu(Lu,2023)titled“Are herbal sRNAs really novel precision medicines?”In this Letter,Lu(2023)commented on our previously published manuscripts(Du et al.,2019;Huang et al.,2019)and concluded that“HJT-sRNA-m1–HJT-sRNA-m8,the eight sRNAs thought to be derived from R.crenulata,are actually derived from animal and/or human beings”.

Large-scale analysis of small RNAs derived from traditional Chinese herbs in human tissues

Plant-derived microRNAs have recently been reported to function in human blood and tissues. Controversy was immediately raised due to possible contamination and the lack of large sample sizes. Here, we report thousands of unique small RNAs derived from traditional Chinese medicine(TCM) herbs found in human blood cells and mouse lung tissues using a large-scale analysis.We extracted small RNAs from decoctions of 10 TCM plants(Ban Zhi Lian, Chai Hu, Chuan Xin Lian, Di Ding Zi Jin, Huang Qin, Jin Yin Hua, Lian Qiao, Pu Gong Ying, Xia Ku Cao, and Yu Xing Cao) and obtained millions of RNA sequences from each herb. We also obtained RNA-Seq data from the blood cells of humans who consumed herbal decoctions and from the lung tissues of mice administered RNAs from herbal decoctions via oral gavage. We identified thousands of unique small RNA sequences in human blood cells and mouse lung tissues. Some of these identified small RNAs from Chuan Xin Lian and Hong Jing Tian could be mapped to the genomes of the herbs, confirming their TCM plant origin. Small RNAs derived from herbs regulate mammalian gene expression in a sequence-specific manner, and thus are a superior novel class of herbal drug components that hold great potential as oral gene-targeted therapeutics, highlighting the important role of herbgenomics in their development.

Clinical and biochemical indexes from 2019-nCoV infected patients linked to viral loads and lung injury

The outbreak of the 2019-nCoV infection began in December 2019 in Wuhan,Hubei province,and rapidly spread to many provinces in China as well as other countries.Here we report the epidemiological,clinical,laboratory,and radiological characteristics,as well as potential biomarkers for predicting disease severity in 2019-nCoV-infected patients in Shenzhen,China.All 12 cases of the 2019-nCoV-infected patients developed pneumonia and half of them developed acute respiratory distress syndrome (ARDS).The most common laboratory abnormalities were hypoalbuminemia,lymphopenia,decreased percentage of lymphocytes (LYM) and neutrophils (NEU),elevated C-reactive protein (CRP) and lactate dehydrogenase (LDH),and decreased CD8 count.The viral load of 2019-nCoV detected from patient respiratory tracts was positively linked to lung disease severity.ALB,LYM,LYM (%),LDH,NEU (%),and CRP were highly correlated to the acute lung injury.Age,viral load,lung injury score,and blood biochemistry indexes,albumin (ALB),CRP,LDH,LYM (%),LYM,and NEU (%),may be predictors of disease severity.Moreover,the Angiotensin Ⅱlevel in the plasma sample from 2019-nCoV infected patients was markedly elevated and linearly associated to viral load and lung injury.Our results suggest a number of potential diagnosis biomarkers and angiotensin receptor blocker (ARB) drugs for potential repurposing treatment of 2019-nCoV infection.

Avian influenza viruses suppress innate immunity by inducingtrans-transcriptional readthrough via SSU72

Innate immunity plays critical antiviral roles. The highly virulent avian influenza viruses (AIVs) H5N1, H7N9, and H5N6 can betterescape host innate immune responses than the less virulent seasonal H1N1 virus. Here, we report a mechanism by whichtranscriptional readthrough (TRT)-mediated suppression of innate immunity occurs post AIV infection. By using cell lines, mouselungs, and patient PBMCs, we showed that genes on the complementary strand (“trans” genes) influenced by TRT were involved inthe disruption of host antiviral responses during AIV infection. The trans-TRT enhanced viral lethality, and TRT abolishmentincreased cell viability and STAT1/2 expression. The viral NS1 protein directly bound to SSU72, and degradation of SSU72 inducedTRT. SSU72 overexpression reduced TRT and alleviated mouse lung injury. Our results suggest that AIVs infection induce TRT byreducing SSU72 expression, thereby impairing host immune responses, a molecular mechanism acting through the NS1-SSU72-trans-TRT-STAT1/2 axis. Thus, restoration of SSU72 expression might be a potential strategy for preventing AIV pandemics.