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Cutaneous wound healing in diabetes is impaired and would develop into nonhealing ulcerations. However, the molecular mechanism underlying the wound-healing process remains largely obscure. Here, we found that cutaneous PDGFRα+ fibroblast-expressing lncRNA-H19 (lncH19) accelerates the wound-healing process via promoting dermal fibroblast proliferation and macrophage infiltration in injured skin. PDGFRα+ cell-derived lncH19, which is lower in contents in the wound-healing cutaneous tissue of patients and mice with type 2 diabetes, is required for wound healing through promoting proliferative capacity of dermis fibroblasts as well as macrophage recruitments. Mechanistically, lncH19 relieves the cell cycle arrest of fibroblasts and increases macrophage infiltration in injured tissues via inhibiting p53 activity and GDF15 releasement. Furthermore, exosomes derived from adipocyte progenitor cells efficiently restore the impaired diabetic wound healing via delivering lncH19 to injured tissue. Therefore, our study reveals a new role for lncRNA in regulating cutaneous tissue repair and provides a novel promising insight for developing clinical treatment of diabetes. [ABSTRACT FROM AUTHOR]

Tyrosol is one of the main polyphenol compounds in white wine and extra virgin olive oil (EVOO), which plays an antioxidant and anti-inflammatory role in vitro. In the present study, we investigated the possible anti-inflammatory mechanism of tyrosol in Escherichia coli (ETEC)-induced diarrhea in mice. ICR mice were randomly divided into control group, ETEC group, and ETEC + Tyrosol group with 10 mice in each group. In addition to the control group, a bacterial diarrhea model was induced in mice by continuous administration of 0.2 ml × 109 CFU/ml ETEC. After 7 days, the ETEC + Tyrosol group was given tyrosol (20 mg/kg) once a day by gavage, during which the body weight of mice and the degree of diarrhea were measured daily. On the 15th day, all animals in this experiment were sacrificed, colon tissue was collected, and colon length was recorded. Our results indicate that tyrosol significantly attenuated the extent of ETEC-induced diarrhea, including inhibition of pro-inflammatory cytokine, repair of the intestinal epithelial mechanical barrier, and significant inhibition of NF-κB activation. This finding is helpful for the development and further application of tyrosol in the treatment of diarrhea. [ABSTRACT FROM AUTHOR]

Purpose: Ulcerative colitis (UC) is a serious health problem with increasing morbidity and prevalence worldwide. The pathogenesis of UC is complex, currently believed to be influenced by genetic factors, dysregulation of the host immune system, imbalance in the intestinal microbiota, and environmental factors. Currently, UC is typically managed using aminosalicylates, immunosuppressants, and biologics as adjunctive therapies, with the risk of relapse and development of drug resistance upon discontinuation. Therefore, further research into the pathogenesis of UC and exploration of potential treatment strategies are necessary to improve the quality of life for affected patients. According to previous studies, Lactobacillus paracasei Jlus66 (Jlus66) reduced inflammation and may help prevent or treat UC. Methods: We used dextran sulfate sodium (DSS) to induce a mouse model of UC to assess the effect of Jlus66 on the progression of colitis. During the experiment, we monitored mouse body weight, food and water consumption, as well as rectal bleeding. Hematoxylin-eosin staining was performed to assess intestinal pathological damage. Protein imprinting and immunohistochemical methods were used to evaluate the protein levels of nuclear factor-kappa B (NF-κB), mitogen-activated protein kinase (MAPK), and tight junction (TJ) proteins in intestinal tissues. Fecal microbiota was analyzed based on partial 16S rRNA gene sequencing. Results: Jlus66 supplementation reduced the degree of colon tissue damage, such as colon shortening, fecal occult blood, colon epithelial damage, and weight loss. Supplementation with Jlus66 reduced DSS-induced upregulation of cytokine levels such as TNF-α, IL-1β, and IL-6 (p < 0.05). The NF-κB pathway and MAPK pathway were inhibited, and the expression of TJ proteins (ZO-1, Occludin, and Claudin-3) was upregulated. 16S rRNA sequencing of mouse cecal contents showed that Jlus66 effectively regulated the structure of the intestinal biota. Conclusion: In conclusion, these data indicate that Jlus66 can alter the intestinal biota and slow the progression of UC, providing new insights into potential therapeutic strategies for UC. [ABSTRACT FROM AUTHOR]

Aging can cause degenerative changes in multiple tissues and organs. Gastrointestinal diseases and dysfunctions are common in the elderly population. In this study, we investigated the effects of Astragalus membranaceus polysaccharide (APS) and Astragalus membranaceus ethanol extract (AEE) on age-related intestinal dysfunction and gut microbiota dysbiosis in naturally aging mice. The energy expenditure and physical activity of 23-month-old C57BL6/J mice were recorded using a metabolic cage system. Pathological changes in the intestine were evaluated using Alcian blue staining. The protein levels of leucine-rich repeats containing G protein-coupled receptor 5 (Lgr5) and Stat3 in the small intestine were determined using immunohistochemistry. The intestinal cell migration distance was assessed using bromodeoxyuridine (BrdU) immunofluorescence staining. The gene transcription levels of intestinal stem cell (ISC) markers and ISC-related signaling pathways were detected using quantitative real-time PCR (qRT-PCR). Microbiota analysis based on 16S rDNA was performed to evaluate the composition of the gut microbiota. APS and AEE improved a series of aging phenotypes in female but not in male aging mice. APS and AEE ameliorate intestinal dysfunction and histopathological changes in aging mice. APS had a more significant anti-aging effect than AEE, particularly on intestinal dysfunction. APS promotes ISC regeneration by activating the IL-22 signaling pathway. Cohousing (CH) experiments further confirmed that APS induced the IL-22 signaling pathway by increasing the abundance of Lactobacillus, thereby promoting the regeneration of ISCs. Our results show that APS may serve as a promising agent for improving age-related intestinal dysfunction. [ABSTRACT FROM AUTHOR]

Inflammatory bowel disease (IBD) is a recurrent disease associated with a potential risk of colorectal cancer. Abelmoschus manihot (AM), a Chinese herbal medicine, is known to alleviate IBD. However, its mechanism of action requires further clarification. Here, we focused on the role of IL-10 and the gut microbiota in the mechanism of action of AM. The effects of AM on intestinal inflammation, mucus production, and gut microbes were evaluated in dextran sodium sulfate (DSS)-induced acute and chronic IBD models and in IL-10-deficient mice (IL-10 − ∕ − ). AM exhibited protective effects on acute and chronic models of IBD in wild-type mice by restoring body weight and colon length, promoting IL-10 secretion, and decreasing TNF- α levels. Moreover, AM alleviated inflammatory infiltration, increased mucin 2 transcription, and increased the number of goblet cells in the colon. On the contrary, these effects were diminished in IL-10 − ∕ − mice, which implied that the effect of AM on intestinal inflammation is IL-10-dependent. A gut microbial sequencing analysis showed that gut microbial dysbiosis was modulated by AM intervention. The regulatory effects of AM on Eggerthellaceae, Sutterellaceae, Erysipelotrichaceae, Burkholderiaceae, Desulfovibrionaceae, and Enterococcaceae were dependent on IL-10. These results revealed that AM ameliorated IBD and modulated gut microbes by promoting IL-10 secretion, indicating that AM has the potential to improve IBD and that AM is IL-10-dependent. [ABSTRACT FROM AUTHOR]

In this study, the expression of Cripto-1 and the role of macrophage polarization in immune response after allogeneic transfusion were analyzed by constructing a mouse model of allogeneic transfusion. In order to analyze the effects of miR-449a on the PI3K/AKT/NF-κB signaling pathway and the expression of downstream related regulatory factors under normal and abnormal conditions, we adopt in vitro and in vivo experiments separately. The molecular mechanism of PI3K/AKT/NF-κB signaling pathway was analyzed by blocking or activating gene expression and western blotting. Experiment in vitro has confirmed that inhibition of miR-449a increased the protein expression of Cripto-1. In vivo experiments confirmed that allogeneic transfusion reduced the expression of Cripto-1, which further inhibited NF-κB signaling pathway through AKT/PI3K phosphorylation, regulated macrophage polarization, inhibited M1 polarization of macrophages, promoted M2 polarization, and thus affected immune response of the body. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance The leaves of Nelumbo nucifera Gaertn are recorded in the earliest written documentation of traditional Chinese medicinal as “Ben Cao Gang Mu”, a medicinal herb for blood clotting, dysentery and dizziness. Recently, nuciferine (NF), one of N. nucifera Gaertn leaf extracts has been shown to possess several pharmacological properties, including anti-viral and anti-cancer. The aim of this study is to investigate the underlying molecular mechanism of the anti-cancer activity of NF in NSCLC progression induced by nicotine Materials and methods The effect of NF on proliferation of A549 (human lung adenocarcinoma epithelial cell line) pretreated with or without nicotine was detected by tumor cell proliferation assay. TOP-Flash reporter assay was applied to investigate the activity of Wnt/β-catenin signaling in tumor cells in the presence of NF and/or nicotine. Apoptosis was measured using a FITC-Annexin V and PI detection kit by flow cytometry. In addition, mRNA or protein expression levels were respectively tested by quantitative RT-PCR or western blot. In vivo experiments, tumor samples were fixed in formalin and embedded in paraffin for additional analyses by immunohistochemistry and TUNEL staining. Results NF significantly inhibited the proliferation of NSCLC cells in the presence of nicotine, suppressed the activity of Wnt/β-catenin signaling, enhanced the stabilization of Axin, and induced apoptosis. NF down-regulated the expression levels of β-catenin and its downstream targets including c-myc, cyclin D and VEGF-A. NF also decreased the ratio of Bcl-2/Bax, which may explain the pro-apoptosis effect of NF. In tumor xenograft nude mice, NF not only inhibited the growth of non-small cell lung cancer (NSCLC) cells, but also remarkably alleviated the injury induced by nicotine in liver function. Conclusions NF has the remarkable effect to inhibit nicotine-induced NSCLC progression, which was due to its ability to reduce the activity of Wnt/β-catenin signaling. Thus, the work stated here emphasizes the importance of this traditional medicine and presents a potential novel alternative to NSCLC prevention and therapy. [ABSTRACT FROM AUTHOR]

Ethnopharmacological relevance Psammosilene tunicoides is one of the important ingredients of a famous Chinese traditional medicine formulation “Yunnan Baiyao”. Also, this plant is commonly used as an anodyne and hemostatic agent in southwest China. Currently, little toxicological information is available on its safety following prolonged use. Aim of the study In this study, we sought to evaluate the toxicity of the three different parts of Psammosilene tunicoides : Psammosilenes Radix (PR), Psammosilenes Radix with Cortex (PRC) and Psammosilenes Cortex (PC) by acute and sub-acute toxicity studies. Materials and methods In the acute toxicity study, mice were orally administrated with different doses of PR, PRC and PC. General behavior and mortality were observed up to 14 days. In sub-acute toxicity study, these aqueous extracts were given orally as a single administration to rats at doses of 0.3, 0.6 and 1.2 g/kg/day, respectively, for 28 days. General behavior, body weight, biochemical, hematological, organ coefficients and pathological morphology parameters were detected. Results In acute study, single oral administration of the aqueous extract of PR, PRC and PC caused dose-dependent general behavior adverse effects and mortality. The LD50 values of PR, PRC and PC were 4.64 g/kg, 4.85 g/kg and 6.40 g/kg, respectively. In sub-acute study, the administration of the extract of PR, PRC and PC during 28 days at all doses reduced spontaneous activities with both genders. Occasional nasal secretion with blood at high doses (1.2 g/kg) of PR, PRC and PC were observed. Daily single oral administration provoked varying degrees of growth retardation in female rats. The relative heart and spleen weight in the female rats were reduced after the administration. On the hematological and biochemical analyses, the administration of the extract of PR, PRC and PC during 28 days mainly caused variation of indexes in female rats. Histopathological analysis has shown vascular congestion in heart, thickened alveolar wall and emphysema in lung, and vascular congestion in kidney of rats after sub-acute oral administrations. Conclusions As shown in the results, Psammosilene tunicoides has a toxic potential in acute and sub-acute oral administrations. However, there is no direct relationship between toxicity and the cortex. Daily oral administration of three different parts from Psammosilene tunicoides (PR, PRC and PC) may cause damages to heart, lung and kidney in rats. Thus these extracts should be used with caution. [ABSTRACT FROM AUTHOR]

Background: Alcohol abuse is a serious health problem worldwide that causes a variety of physical and mental disorders. Research has shown that the brain-derived neurotrophic factor (BDNF) plays an important role in alcohol addiction. The BDNF precursor (proBDNF) exhibits different actions than BDNF through separate receptors and pathways in the central nervous system. However, the effects of proBDNF and BDNF in alcohol addiction are not fully known.Objectives: The objective was to identify the expression patterns and effects of proBDNF and BDNF after chronic alcohol exposure.Methods: A total of 40 male adult mice were studied. A mouse psychomotor sensitization (PS) model was established to explore the effects of BDNF and proBDNF treatment following chronic alcohol exposure. Reverse transcription PCR (RT-PCR) was performed to measure mRNA levels for BDNF, TrkB, P75NTR, and sortilin in the prefrontal cortex, hippocampus, and dorsal striatum of Kunming mice after chronic alcohol exposure.Results: In Kunming mice, chronic alcohol exposure up-regulated BDNF and TrkB mRNA levels in the prefrontal cortex, but decreased sortilin and P75 mRNA levels in the dorsal striatum. No changes in mRNA levels were found in other measured brain regions in the alcohol and control groups.Conclusion: Chronic alcohol exposure induced the region-specific expression of BDNF and proBDNF and their respective receptors in the brain. These results suggest that BDNF and proBDNF signaling pathways may play major roles in alcohol preference and addiction. [ABSTRACT FROM AUTHOR]

Quercitrin is a well-known flavonoid that is contained in Flos Albiziae, which has been used for the treatment of anxiety. The present study investigated the anxiolytic-like effects of quercitrin in experimental models of anxiety. Compared with the control group, repeated treatment with quercitrin (5.0 and 10.0 mg/kg/day, p.o.) for seven days significantly increased the percentage of entries into and time spent on the open arms of the elevated plus maze. In the light/dark box test, quercitrin exerted an anxiolytic-like effect at 5 and 10 mg/kg. In the marble-burying test, quercitrin (5.0 and 10.0 mg/kg) also exerted an anxiolytic-like effect. Furthermore, quercitrin did not affect spontaneous locomotor activity. The anxiolytic-like effects of quercitrin in the elevated plus maze and light/dark box test were blocked by the serotonin-1A (5-hydroxytryptamine-1A (5-HT1A)) receptor antagonist WAY-100635 (3.0 mg/kg, i.p.) but not by the γ-aminobutyric acid-A (GABAA) receptor antagonist flumazenil (0.5 mg/kg, i.p.). The levels of brain monoamines (5-HT and dopamine) and their metabolites (5-hydroxy-3-indoleacetic acid, 3,4-dihydroxyphenylacetic acid, and homovanillic acid) were decreased after quercitrin treatment. These data suggest that the anxiolytic-like effects of quercitrin might be mediated by 5-HT1A receptors but not by benzodiazepine site of GABAA receptors. The results of the neurochemical studies suggest that these effects are mediated by modulation of the levels of monoamine neurotransmitters. [ABSTRACT FROM AUTHOR]

Salvia miltiorrhiza Bge. as a traditional Asian medicinal plant, roots and rhizomes (Danshen) are used to treat chronic hepatitis and coronary heart disease. In recent years, the medicinal value of S. miltiorrhiza stems and leaves total phenolic acids extract (JF) similar to roots and rhizomes has received increasing attention. S. miltiorrhiza roots and rhizome tanshinone extract (DT) has a good anti-inflammatory effect. To explore the therapeutic effect and possible molecular mechanisms of JF and DT alone or in combination on dextran sulfate sodium (DSS)-induced colitis mice. Colitis was induced by received 2% DSS in drinking water for 7 consecutive days. Then mice were administered orally for 7 days. Disease activity index (DAI) scores and body weight were recorded daily. After the end of the experiment, colon was removed, colon length was measured and histopathological analysis was performed. Inflammatory factors expression was determined by ELISA, its mRNA expression was detected by real-time quantitative PCR, and the expression of related proteins on TLR4/PI3K/AKT/mTOR signal was analyzed by Western blot. Treatment with JF and DT alone or in combination reduced DAI scores, increase body weight, improved colon shortening, and decreased colon histology scores. In addition, the expression level of inflammatory factors was inhibited. The combination of JF and DT had a better inhibitory effect on inflammatory factors compared to JF alone. We also found that DT alone and JF combined with DT inhibited TLR4/PI3K/AKT/mTOR signaling-related proteins expression levels (including TLR4, p-PI3K p110α/PI3K p110α, p-AKT (ser473)/AKT, mTOR, p-mTOR, NF-κB p65), showing an effective anti-inflammatory effect. We demonstrated for the first time that, JF and DT alone or in combination effectively ameliorated DSS-induced ulcerative colitis in mice, possibly by inhibiting the TLR4/PI3K/AKT/mTOR signaling pathway. Image 1 [ABSTRACT FROM AUTHOR]