Fibrosis is characterized as an aberrant reparative process involving the direct replacement of damaged or deceased cells with connective tissue, leading to progressive architectural remodeling across various tissues and organs. This condition imposes a substantial burden, resulting in considerable morbidity and mortality. Ginseng (Panax ginseng C. A. Meyer), renowned for its medicinal properties, has been incorporated as a key component in Chinese patent medicines to mitigate fibrotic diseases. Ginsenosides, the primary bioactive compounds in ginseng, have garnered significant attention. Over the past five years, extensive research has explored the pharmaceutical potential of ginsenosides in diverse organ fibrosis conditions, including liver, myocardial, renal, and pulmonary fibrosis. Studies have elucidated that ginsenosides demonstrate potential effects on inflammatory responses stemming from parenchymal cell damage, myofibroblast activation leading to extracellular matrix (ECM) production, and myofibroblast apoptosis or inactivation. Additionally, potential downstream targets and pathways associated with these pathological processes have been identified as being influenced by ginsenosides. This review presents a comprehensive overview of the efficacious treatments utilizing ginsenosides for various tissue fibrosis types and their potential anti-fibrotic mechanisms. Furthermore, it offers a reference for the development of novel candidate drugs for future organ fibrosis therapies.
Ginsenosides/pharmacology* ; Humans ; Fibrosis/drug therapy* ; Animals ; Panax/chemistry* ; Drugs, Chinese Herbal/therapeutic use*

Quantum dot-based single-virus tracking has become a practical method to explore the molecular mechanism of virus entry into cells,because it can realize virion imaging in living cells.Mink enteritis virus(MEV)is a single-stranded DNA virus with strong environmental resistance,which has caused huge economic losses for the global mink farming industry.Although epidemio-logic and clinical aspects of MEVs have been studied,the mechanisms by which it infect target cells remain unclear.In this study,we implemented quantum dot labeling of mink enteritis virus u-sing the biotin-streptomycin affinity system and monitored the viral infection process in host cells.We found that MEV first attaches to the cell membrane and enters the cell by endocytosis.Live cell images showed quantum dot(QD)-MEV movement along microtubules,and viral infection was also inhibited by treatment with the microtubule inhibitor nocodazole,whereas the addition of the microfilament inhibitor CytoD had no effect on infection,suggesting that MEV transport is de-pendent on microtubules rather than microfilaments.Another imaging results showed that MEV co-localized with Rab5 and Rab7 in host cells,suggesting that the endosomal system is required for MEV internalization.Biochemical analyses showed that viral infection was significantly inhibited after pretreatment of host cells with the endosomal acidification inhibitors NH4 Cl and chloro-quine,suggesting that MEV invasion requires an acidic environment in the endosomes.Our results indicated that MEV enters early and late endosomes after entering the cell membrane,and that in-tracellular translocation is microtubule-dependent,which may in turn uncover a novel target for antiviral treatment.

Quantum dot-based single-virus tracking has become a practical method to explore the molecular mechanism of virus entry into cells,because it can realize virion imaging in living cells.Mink enteritis virus(MEV)is a single-stranded DNA virus with strong environmental resistance,which has caused huge economic losses for the global mink farming industry.Although epidemio-logic and clinical aspects of MEVs have been studied,the mechanisms by which it infect target cells remain unclear.In this study,we implemented quantum dot labeling of mink enteritis virus u-sing the biotin-streptomycin affinity system and monitored the viral infection process in host cells.We found that MEV first attaches to the cell membrane and enters the cell by endocytosis.Live cell images showed quantum dot(QD)-MEV movement along microtubules,and viral infection was also inhibited by treatment with the microtubule inhibitor nocodazole,whereas the addition of the microfilament inhibitor CytoD had no effect on infection,suggesting that MEV transport is de-pendent on microtubules rather than microfilaments.Another imaging results showed that MEV co-localized with Rab5 and Rab7 in host cells,suggesting that the endosomal system is required for MEV internalization.Biochemical analyses showed that viral infection was significantly inhibited after pretreatment of host cells with the endosomal acidification inhibitors NH4 Cl and chloro-quine,suggesting that MEV invasion requires an acidic environment in the endosomes.Our results indicated that MEV enters early and late endosomes after entering the cell membrane,and that in-tracellular translocation is microtubule-dependent,which may in turn uncover a novel target for antiviral treatment.

Objective:To investigate immunomodulatory effects of methionine enkephalin(MENK)on macrophages,and to explore effect of opsonizing receptors in anti-influenza virus infection of macrophages.Methods:Potential targets for antiviral effects of MENK on macrophages were explored by network pharmacology.Proteomics analysis was used to identify differentially expressed pro-teins(DEPs)in macrophages of MENK-PR8 and PR8 groups.DEPs were analyzed by bioinformatics,and key factors were verified by qPCR and Western blot.Results:MENK had 85 intersection targets with macrophages and influenza viruses,of which 7 were related to phagosome pathway(mmu04145).A total of 215 DEPs were identified by mass spectrometry,which were highly enriched in phago-some(mmu04145)and interaction of viral proteins with cytokines and cytokine receptors(mmu04061)pathways.qPCR and Western blot showed that Fc gamma receptor(FcγR)and complement receptor(CR3)related to phagosome were highly expressed.Conclu-sion:MENK enhances function of phagocytosis and killing virus by upregulating opsonizing receptors via opioid receptor,suggesting that MENK can serve as an immune modulator or a novel preventive drug for influenza viruses.

Objective:To investigate immunomodulatory effects of methionine enkephalin(MENK)on macrophages,and to explore effect of opsonizing receptors in anti-influenza virus infection of macrophages.Methods:Potential targets for antiviral effects of MENK on macrophages were explored by network pharmacology.Proteomics analysis was used to identify differentially expressed pro-teins(DEPs)in macrophages of MENK-PR8 and PR8 groups.DEPs were analyzed by bioinformatics,and key factors were verified by qPCR and Western blot.Results:MENK had 85 intersection targets with macrophages and influenza viruses,of which 7 were related to phagosome pathway(mmu04145).A total of 215 DEPs were identified by mass spectrometry,which were highly enriched in phago-some(mmu04145)and interaction of viral proteins with cytokines and cytokine receptors(mmu04061)pathways.qPCR and Western blot showed that Fc gamma receptor(FcγR)and complement receptor(CR3)related to phagosome were highly expressed.Conclu-sion:MENK enhances function of phagocytosis and killing virus by upregulating opsonizing receptors via opioid receptor,suggesting that MENK can serve as an immune modulator or a novel preventive drug for influenza viruses.

Objective To observe the effects of electroacupuncture at"Ciliao","Zhongji","Sanyinjiao"and"Dazhui"on urodynamics and expression of ERK/CREB/Bcl-2 pathway in spinal cord tissue of neurogenic bladder rats after suprasacral spinal cord injury.Methods Sixty female SD rats randomly selected 24 and divided into blank group and sham-operation group(12 rats in each group),the remaining 36 rats were subjected to surgical modeling.After modeling,rats were randomly divided into the model group and the electroacupuncture group,with 12 rats in each group.The electroacupuncture group received unilateral electroacupuncture stimulation at acupoints"Ciliao","Zhongji","Sanyinjiao",and"Dazhui"for 30 minutes each time,once a day,for 7 consecutive days.After administration,urodynamic testing was performed,HE staining was used to observe the morphology of bladder detrusor tissue,TUNEL method was used to detected apoptosis in spinal cord tissue,Western blot was used to detected expressions of p-ERK1/2,p-CREB,p-p90Rsk,CRE,Bcl-2,and Bax proteins in spinal cord tissue.Results Compared with the sham-operation group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the model group increased significantly(P<0.01),while the maximum capacity and compliance of the bladder decreased significantly(P<0.01);the structure of bladder smooth muscle cells was severely damaged and disorderly arranged,accompanied by a large amount of inflammatory cell infiltration;the apoptosis rate of spinal cord tissue cells significantly increased(P<0.01),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue were significantly decreased,while the expression of Bax protein significantly increased(P<0.01).Compared with the model group,the basal pressure,maximum pressure,and leakage point pressure of the bladder in the electroacupuncture group decreased significantly(P<0.05),while the maximum capacity and compliance of the bladder increased significantly(P<0.05,P<0.01);the integrity of bladder smooth muscle cells was enhanced,the degree of cell edema was reduced,and inflammatory cell infiltration was reduced;the apoptosis rate of spinal cord tissue cells was significantly reduced(P<0.05),and the expressions of p-ERK1/2,p-p90Rsk,p-CREB,CRE,and Bcl-2 proteins in spinal cord tissue significantly increased,while the expression of Bax protein was significantly decreased(P<0.05,P<0.01).Conclusion Electroacupuncture can promote the repair of bladder detrusor tissue in rats with neurogenic bladder model after suprasacral spinal cord injury,increase the maximum capacity and compliance of the bladder,alleviate the high pressure state in the bladder,and its mechanism is related to activating the ERK/CREB/Bcl-2 pathway,reducing secondary apoptosis of damaged neurons,effectively improving bladder innervation,and protecting bladder function.

ObjectiveThe differential expression of microRNAs （miRNAs） between the active stage and the remission stage of ulcerative colitis （UC） was analyzed by bioinformatics method， and the regulatory relationship was constructed by screening the differentially expressed genes （DEGs）. The mechanism of Xizhuo Jiedu recipe in the treatment of UC was speculated and verified by animal experiments. MethodThe miRNAs data set of colonic mucosa tissue of UC patients was obtained from the gene expression database （GEO）， and the most differentially expressed miRNAs were screened by GEO2R， Excel， and other tools as research objects. TargetScan， miRTarbase， miRDB， STRING， TRRUST， and Matescape databases were used to screen key DEGs， predict downstream transcription factors （TFs）， gene ontology （GO）， and conduct Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis. The key signaling pathways were selected for animal experiments. In animal experiments， the UC mouse model was prepared by making the mouse freely drink 2.5% dextran sodium sulfate （DSS）. Xiezhu Jiedu recipe and mesalazine were given by gavage for seven days， and the inflammatory infiltration of colonic mucosa was observed by hematoxylin-eosin （HE） staining. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect the mRNA expression of miR-155-5p in colon tissue. Immunohistochemistry and Western blot were used to detect the protein expression levels of cytokine signal transduction inhibitor （SOCS1）， phosphorylated transcriptional signal transductor and activator 3 （p-STAT3）， phosphorylated Janus kinase 2 （p-JAK2）， and retinoic acid-associated orphan receptor-γt （ROR-γt）. The expression levels of transforming growth factor-β （TGF-β）， interleukin-17 （IL-17）， interleukin-6 （IL-6）， and interleukin-10 （IL-10） in serum were detected by enzyme linked immunosorbent assay （ELISA）. ResultThe GSE48957 dataset was screened from the GEO database， and miR-155-5p was selected as the research object from the samples in the active and remission stages. 131 DEGs were screened. The GO/KEGG enrichment analysis was closely related to biological processes such as positive regulation of miRNA transcription and protein phosphorylation， as well as signaling pathways such as stem cell signaling pathway， IL-17 signaling pathway， and helper T cell 17 （Th17） cell differentiation. The Matescape database was used to screen out 10 key DEGs， among which SOCS1 was one of the key DEGs of miR-155-5p. Further screening of the TFS of key DEGs revealed that STAT3 was one of the main TFs of SOCS1. The results of animal experiments showed that Xiezhu Jiedu Recipe could effectively down-regulate the mRNA expression of miR-155-5p and protein expression of p-STAT3， p-JAK2， and ROR-γt in colon tissue of UC mice and the expression of IL-17 and IL-6 in serum of UC mice， up-regulate the protein expression of SOCS1 and the expression of TGF-β and IL-10， increase the level of anti-inflammatory factors， and reduce inflammatory cell infiltration. ConclusionIt is speculated that Xizhuo Jiedu recipe may interfere with SOCS1 by regulating the expression of miR-155-5p in UC mice， inhibit the phosphorylation of STAT3， inhibit the differentiation of CD4⁺ T cells into Th17 cells， reduce the levels of pro-inflammatory factors （IL-17 and IL-6）， and increase the levels of anti-inflammatory factors （TGF-β and IL-10）. As a result， the inflammation of colon mucosa in UC mice was alleviated.

OBJECTIVE: To explore the clinical characteristics and genetic basis of two brothers featuring X-linked alpha thalassemia mental retardation (ATR-X) syndrome. METHODS: An infant who had presented at the Qilu Children's Hospital in 2020 for unstable upright head and inability to roll over and his family were selected as the study subjects. The clinical features of the child and one of his brothers were summarized, and their genomic DNA was subjected to targeted capture and next generation sequencing (NGS). RESULTS: The brothers had presented with mental retardation and facial dysmorphisms. NGS revealed that they had both harbored a hemizygous c.5275C>A variant of the ATRX gene located on the X chromosome, which was inherited from their mother. CONCLUSION The siblings were diagnosed with ATR-X syndrome. The discovery of the c.5275C>A variant has enriched the mutational spectrum of the ATRX gene.
Humans ; Infant ; Male ; alpha-Thalassemia/diagnosis* ; Ataxia Telangiectasia Mutated Proteins/genetics* ; East Asian People ; Intellectual Disability/genetics* ; Mental Retardation, X-Linked/diagnosis* ; Pedigree ; X-linked Nuclear Protein/genetics*

It is an urgent demand worldwide to control the coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus. The 3-chymotrypsin-like protease (3CL^pro) and papain-like protease (PL^pro) are key targets to discover SARS-CoV-2 inhibitors. After screening 12 Chinese herbal medicines and 125 compounds from licorice, we found that a popular natural product schaftoside inhibited 3CL^pro and PL^pro with IC₅₀ values of 1.73 ± 0.22 and 3.91 ± 0.19 μmol/L, respectively, and inhibited SARS-CoV-2 virus in Vero E6 cells with EC₅₀ of 11.83 ± 3.23 μmol/L. Hydrogen-deuterium exchange mass spectrometry analysis, quantum mechanics/molecular mechanics calculations, together with site-directed mutagenesis indicated the antiviral activities of schaftoside were related with non-covalent interactions with H41, G143 and R188 of 3CL^pro, and K157, E167 and A246 of PL^pro. Moreover, proteomics analysis and cytokine assay revealed that schaftoside also regulated immune response and inflammation of the host cells. The anti-inflammatory activities of schaftoside were confirmed on lipopolysaccharide-induced acute lung injury mice. Schaftoside showed good safety and pharmacokinetic property, and could be a promising drug candidate for the prevention and treatment of COVID-19.

Psoriasis is an autoimmune disease characterized by chronic skin inflammation, and its etiology and pathogenesis have not been fully elucidated to date. In the previous study, rhIL23R-CHR/Fc fusion protein had been found to significantly relieve the symptoms of psoriasis mice and the pharmacological mechanism had been initially elucidated.In this study, we established a psoriasis cell model (Act-HaCaT) using TNF-α-activated human immortalized keratinocytes (HaCat).In our current study, the lncRNA that plays a key role in the regulation of Act-HaCaT function by the rhIL23R-CHR/Fc fusion protein was screened by transcriptome sequencing combined with qRT-PCR.The results showed that rhIL23R-CHR/Fc fusion protein significantly inhibited cell proliferation and inflammatory factor production in Act-HaCaT.lncRNA ENST00000522718 was obtained by screening, and knockdown of ENST00000522718 was found to significantly inhibit cell proliferation and inflammatory factor production.Our findings suggest that ENST00000522718 plays an important role in the pathological mechanism of psoriasis.