OBJECTIVE To explore the ameliorative effect and potential mechanism of vitexin on inflammation in ulcerative colitis （UC） mice. METHODS The UC mice model was established by continuous administration of 3% dextran sulfate sodium solution for 5 days. Mice with successful modeling were randomly divided into UC group， vitexin low- and high-dose groups （vitexin-L and vitexin-H groups， 40， 80 mg/kg）， mesalazine group （400 mg/kg）， and vitexin-H+recombinant Jagged canonical Notch ligand 1 （rJagged-1） group （vitexin-H+rJagged-1 group， 80 mg/kg vitexin+1 mg/kg rJagged-1）， with 12 mice in each group. Another 12 normal mice were used as the control （CK） group. Mice in each group were administered the corresponding drugs or the corresponding drugs and normal saline by gavage and intraperitoneal injection once daily for 7 consecutive days. General conditions were observed during the experiment. At 24 h after the last administration， the disease activity index （DAI） score was evaluated. Colonic histopathological morphology was observed and scored. Macrophage polarization levels in the spleen and colon tissues were measured. The protein expressions of interleukin-6 （IL-6）， IL-10， tumor necrosis factor-α （TNF-α）， transforming growth factor-β 1 （TGF-β 1 ）， Jagged-1， Notch1 and Notch intracellular domain （NICD） in colonic tissues were determined. RESULTS Compared with the UC group， the symptoms （reduced food and water intake， dull fur， etc.） and pathological changes （epithelial cell shedding， inflammatory cell infiltration， etc.） were significantly improved in the vitexin-L， vitexin-H and mesalazine groups. DAI scores， colonic histopathological scores， M1 macrophage contents in spleen tissue， M1/M2 macrophage ratios， M1 macrophage proportions in colon tissue， and protein expressions of IL-6， TNF-α， Jagged-1， Notch1 and NICD in colon tissue were significantly decreased （ P ＜0.05）. Meanwhile， the M2 macrophage contents in spleen tissue， M2 macrophage proportions in colon tissue， and protein expressions of IL-10 and TGF-β 1 in colon tissue were significantly increased （ P ＜0.05）. Moreover， the improvement effects in the vitexin-H and mesalazine groups were significantly superior to those in the vitexin-L group （ P ＜0.05）. Compared with the vitexin-H group， the above symptoms and pathological changes were aggravated， and all quantitative indicators were significantly reversed in the vitexin-H+rJagged-1 group （ P ＜0.05）. CONCLUSIONS Vitexin can ameliorate the inflammation of UC mice， which is associated with its inhibition of the Jagged-1/Notch1 pathway and regulation of macrophage polarization （inhibition of M1-type polarization and promotion of M2-type polarization）.

OBJECTIVE To investigate the improvement effects and mechanism of Xiangsha yiwei tang on gastric mucosal injury in rats with chronic atrophic gastritis （CAG）. METHODS Rats were randomly assigned into normal control group， model group， Xiangsha yiwei tang low-， medium- and high-dose groups （6， 12， 18 g/kg， calculated by crude drug）， and high-dose group of Xiangsha yiwei tang+740 Y-P [Xiangsha yiwei tang 18 g/kg+transforming growth factor β1/phosphatidyl inositol 3 kinase/ protein kinase B（TGF-β1/PI3K/Akt） pathway activator group 740 Y-P 10 mg/kg]， with 18 rats in each group. Rats in each group were administered the corresponding drugs via oral gavage or injection， once daily， for 4 consecutive weeks. Gastric mucosal blood flow， the levels of serum gastrointestinal hormones [including motilin （MTL）， gastrin （GAS）， and pepsinogen （PP）]， as well as inflammatory cytokines [including tumor necrosis factor- α （TNF- α）， interleukin-1β （IL-1β）， IL-6] in rats were measured. Pathological damage to gastric mucosal tissue was observed in rats； the apoptotic rate of gastric mucosal cells was detected. The expressions of TGF-β1/PI3K/Akt signaling pathway-related proteins and apoptosis-related proteins [including B-cell lymphoma-2 （Bcl-2） and Bcl-2-associated X protein （Bax）] in the gastric mucosal tissues of rats were assessed. RESULTS Compared with normal control group， model group had abnormal gastric mucosal tissue structure， with shedding of gastric mucosal epithelial cells， and prominent infiltration of inflammatory cells. Gastric mucosal blood flow， the serum levels of MTL， GAS， PP， and Bcl-2 protein expression were lowered significantly， while serum levels of TNF-α， IL-1β and IL-6， apoptosis rate， protein expressions of Bax and TGF-β1， the phosphorylations of PI3K and Akt were increased significantly （P＜0.05）. Compared with model group， Xiangsha yiwei decoction groups exhibited attenuated histopathological injuries in gastric mucosal tissues， reduced inflammatory cell infiltration， and significant improvements in the aforementioned quantitative parameters （P＜0.05）. Compared with high-dose group of Xiangsha yiwei tang， high-dose group of Xiangsha yiwei decoction combined with 740 Y-P exhibited significantly aggravated histopathological injuries in gastric mucosal tissues， and the aforementioned quantitative parameters were markedly reversed （P＜0.05）. CONCLUSIONS Xiangsha yiwei tang can alleviate gastric mucosal damage in CAG rats， and its mechanism of action is related to the inhibition of TGF-β1/PI3K/Akt signaling pathway.

Microglia, the resident immune cells in the central nervous system (CNS), rapidly transition from a resting to an active state in the acute phase of ischemic brain injury. This active state mediates a pro-inflammatory response that can exacerbate the injury. Targeting the pro-inflammatory response of microglia in the semi-dark band during this acute phase may effectively reduce brain injury. Shionone (SH), an active ingredient extracted from the dried roots and rhizomes of the genus Aster (Asteraceae), has been reported to regulate the inflammatory response of macrophages in sepsis-induced acute lung injury. However, its function in post-stroke neuroinflammation, particularly microglia-mediated neuroinflammation, remains uninvestigated. This study found that SH significantly inhibited lipopolysaccharide (LPS)-induced elevation of inflammatory cytokines, including interleukin-1β (IL-1β), tumor necrosis factor-α (TNF-α), and inducible nitric oxide synthase (iNOS), in microglia in vitro. Furthermore, the results demonstrated that SH alleviated infarct volume and improved behavioral performance in middle cerebral artery occlusion (MCAO) mice, which may be attributed to the inhibition of the microglial inflammatory response induced by SH treatment. Mechanistically, SH potently inhibited the phosphorylation of serine-threonine protein kinase B (AKT), mammalian target of rapamycin (mTOR), and signal transducer and activator of transcription 3 (STAT3). These findings suggest that SH may be a potential therapeutic agent for relieving ischemic stroke (IS) by alleviating microglia-associated neuroinflammation.
Animals ; Microglia/immunology* ; Mice ; Male ; Mice, Inbred C57BL ; Brain Ischemia/immunology* ; Neuroinflammatory Diseases/drug therapy* ; Neuroprotective Agents/administration & dosage* ; Interleukin-1beta/genetics* ; STAT3 Transcription Factor/genetics* ; TOR Serine-Threonine Kinases/genetics* ; Tumor Necrosis Factor-alpha/genetics* ; Proto-Oncogene Proteins c-akt/immunology* ; Nitric Oxide Synthase Type II/genetics* ; Lipopolysaccharides

Objective To investigate the role of scar epithelial cells and its potential molecular mechanisms in the efficacy of low-energy CO2 fractional laser treating post-burn scars.Methods The model of post-major burn scars on the back of rat was established.Three rats with post-major burn scars received 30 mJ low-energy CO2 fractional laser treatment to detect the activation of scar epidermal cells.Epidermal tissue of scars was isolated for RNA sequencing to screen activated pathways.Subsequently,18 rats with post-major burn scars were randomly divided into 3 groups(n=6):the control group without laser treatment,the laser group receiving 30 mJ CO2 fractional laser treatment,and the laser+inhibitor group receiving laser treatment and intra-scar injection of IWR-1(a Wnt/β-catenin pathway inhibitor),to verify the activation status and effects of the selected pathways.Hematoxylin-eosin staining,Masson staining,and Western blotting were used to detect the proliferation of epithelial cells and fibroblasts,the activation of Wnt/β-catenin pathway,as well as the improvement of scar profiles.Results After low-energy laser treatment,there was a significant increase in the number of Ki67-positive,proliferating cell nuclear antigen(PCNA)-positive,cytokeratin 19(CK19)-positive,and p63-positive cells in the scar epithelial tissue.RNA sequencing coupled with literature analysis identified Wnt/β-catenin pathway as a potential candidate pathway.In the confirmatory experiment,compared to the control group,the Wnt/β-catenin pathway was activated in scar epithelial cells in the laser group 5 d post-laser intervention.After 30 d laser intervention,dermal collagen exhibited a more loosened arrangement,with reduced dermal thickness and significantly less α-smooth muscle actin(α-SMA)-positive fibroblasts compared to the control group.CollagenⅠ,collagen Ⅲ,and the relative ratio of collagen Ⅰ to Ⅲ in the laser group were at a lower level than those in the control group.Administration of the Wnt/β-catenin pathway inhibitor blocked the activation of the Wnt/β-catenin pathway induced by low-energy laser,the proliferation of scar epithelial cells and the improvement of scar profiles.Conclusion Low-energy CO2 fractional laser treatment can activate the Wnt/β-catenin pathway of scar epithelial cells,thereby activating epithelial cells and yielding significant scar improvements.

Nitroxide radicals are a kind of stable organic free radicals.Due to the presence of N-O·and unpaired electrons in its structure,it has many characteristics,and thus can be used as a spin marker to explore the mechanism of biological reactions;with its magnetic properties,it can be used for the development of multifunctional magnetic molecular materials and used as a polymerization inhibitor and catalyst in organic reactions.More importantly,it has a variety of biological activities such as anti-oxidation and anti-tumor,and so has attracted much attention in the research and development of new drugs.For example,the spin labeling of nitroxide radicals on anticancer drug podophyllotoxin can enhance the efficacy and reduce the toxicity,and can be easily to be absorbed by the body,thus obtaining a new anti-cancer drug 4-[4″-(2″,2″,6″,6″-tetramethyl-1″-piperidinyloxy nitroxide radical)amino]-4′-demethyl epipodophyllotoxin(GP-7).It is an effective way to seek new drugs by introducing pharmacophore to modify nitroxide radicals or it can be spin-labeled on active natural products to obtain new compounds with high efficiency and low toxicity.The research progress of derivatives and its biological activitives of nitroxide radicals are summarized,aiming to provide theoretical basis for the developing and utilizing of nitroxide radicals and searching for new drugs.

To evaluate the application value of metal clip combined with suture and rubber coil as a simple traction device in endoscopic submucosal dissection (ESD) for intestinal mucosal lesions, a total of 56 patients with early colonic cancer and precancerous lesions who received ESD in Jiangyin People's Hospital from January 2021 to July 2022 were randomly divided into the control group ( n=28, conventional ESD) and the traction group ( n= 28, suture and rubber coil as a simple traction device). The total time of ESD, mucosal dissection time, number of submucosal injections, complete resection rate and complications were compared between the two groups. The operation time of the traction group was shorter than that of the control group (74.64±33.25 min VS 117.18±35.75 min, t=4.61, P<0.001). The desection time of mucosa in the traction group was shorter than that in the control group (51.61±24.87 min VS 99.11±32.73 min, t=6.11, P<0.001). The number of submucosal injection in the traction group was less than that of the control group with significant difference (1.68±1.16 VS 4.96±1.41, t=9.57, P<0.001). There was no significant differences in operation area, complete resection rate or complication between the two groups ( P>0.05). The traction assistance technology of metal clip combined with suture and rubber coil can reduce the technical difficulty of colonic ESD and shorten the operation time.

BACKGROUND: Current replacement procedures for stenosis or occluded arteries using prosthetic grafts have serious limitations in clinical applications, particularly, endothelialization of the luminal surface is a long-standing unresolved problem.METHOD: We produced a cell-based hybrid vascular graft using a bioink engulfing adipose-derived mesenchymal stromal cells (ADSCs) and a 3D bioprinting process lining the ADSCs on the luminal surface of GORE-Tex grafts. The hybrid graft was implanted as an interposition conduit to replace a 3-cm-long segment of the infrarenal abdominal aorta in Rhesus monkeys. RESULTS: Complete endothelium layer and smooth muscle layer were fully developed within 21 days post-implantation, along with normalized collagen deposition and crosslinking in the regenerated vasculature in all monkeys. The regenerated blood vessels showed normal functionality for the longest observation of more than 1650 days. The same procedure was also conducted in miniature pigs for the interposition replacement of a 10-cm-long right iliac artery and showed the same long-term effective and safe outcome. CONCLUSION This cell-based vascular graft is ready to undergo clinical trials for human patients.

OBJECTIVES: To explore ferroptosis-related genes in osteoporosis through bioinformatic analysis and in vitro study. METHODS: Osteoporosis-related genes were identified from dataset GSE35958 in the Gene Expression Omnibus database; and the ferroptosis-related genes were identified from the FerrDb database. These were intersected with the differentially expressed genes in GSE35958 to obtain ferroptosis-related genes in osteoporosis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed for the differentially expressed genes. And Spearman correlation and protein-protein interaction network analysis were performed. Then, the hub genes of ferroptosis in osteoporosis were screened by Degree, MNC, EPC, MCC and DMNC in Cytoscape software CytoHubba plugin; and analyzed with receiver operating characteristic (ROC) curves. The bone marrow mesenchymal stem cells from osteoporosis patients (osteoporosis group) and non-osteoporosis patients (control group) were subjected to quantitative reverse transcription polymerase chain reaction to detect the messenger RNA expression of ferroptosis hub genes in both groups. RESULTS: A total of 32 differentially expressed genes related to ferroptosis in osteoporosis were identified, including 26 up-regulated genes and 6 down-regulated genes. GO enrichment analysis showed that the identified genes were mainly involved in intercellular adhesion, lipid metabolism and cytokine response. KEGG enrichment analysis showed that the genes were mainly involved in signaling pathways of adhesive plaques, MAPK, PI3K-Akt, and Wnt. Spearman correlation analysis showed correlation among differentially expressed genes. Six hub genes for ferroptosis in osteoporosis were obtained, namely MAPK3, CDKN1A, MAP1LC3A, TNF, RELA, and TGF-β1. ROC curve analysis showed that these hub genes had good diagnostic performance in osteoporosis and may become potential biomarkers of osteoporosis. In vitro experiments confirmed significant differences in these hub genes between the control group and the osteoporosis group (all P<0.05). CONCLUSIONS This study has identified six ferroptosis-related hub genes in osteoporosis, which may be used as novel biomarkers for the early diagnosis and treatment of osteoporosis.
Osteoporosis/genetics* ; Humans ; Computational Biology ; Ferroptosis/genetics* ; Protein Interaction Maps/genetics* ; Gene Ontology ; Mesenchymal Stem Cells/metabolism* ; Gene Expression Profiling ; Databases, Genetic

Chronic cerebral hypoperfusion leads to white matter injury (WMI), which subsequently causes neurodegeneration and even cognitive impairment. However, due to the lack of treatment specifically for WMI, novel recognized and effective therapeutic strategies are urgently needed. In this study, we found that honokiol and magnolol, two compounds derived from Magnolia officinalis, significantly facilitated the differentiation of primary oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes, with a more prominent effect of the former compound. Moreover, our results demonstrated that honokiol treatment improved myelin injury, induced mature oligodendrocyte protein expression, attenuated cognitive decline, promoted oligodendrocyte regeneration, and inhibited astrocytic activation in the bilateral carotid artery stenosis model. Mechanistically, honokiol increased the phosphorylation of serine/threonine kinase (Akt) and mammalian target of rapamycin (mTOR) by activating cannabinoid receptor 1 during OPC differentiation. Collectively, our study indicates that honokiol might serve as a potential treatment for WMI in chronic cerebral ischemia.
Magnolia ; White Matter ; Brain Ischemia/metabolism* ; Oligodendroglia/metabolism*

This paper summarized the experience in treating bronchiectasis with Mahuang Shengma Decoction （麻黄升麻汤）. The pathogenesis of bronchiectasis is “lung-spleen qi deficiency” as the root， and “phlegm-heat obstructing the lung” as the branch. The key point of treatment is to improve the internal environment of phlegm， heat， and deficiency. According to clinical experience， Mahuang Shengma Decoction is good at raising the yang qi to dissipate fire， clearing the upper and warming the lower， which is in accord with the pathogenesis of bronchiectasis. In clinical practice， Mahuang Shengma Decoction is usually used as the basic formula， and the heat-clearing medicinals and center-warming medicinals of the formula will be adjusted according to the abnormal exuberance of heat or cold of the pathogenesis； and the formula can also be modified in accordance with the symptoms. At the same time， importance should be attached to the application of Mahuang （Herba Ephedrae）， and its dosage should be flexibly adjusted according to the constraint degree of the pathogenic qi， so as to expel the constraint fire， bank up earth to generate metal， regulate heat and cold simultaneously， and treat both the root and the branch.