Paeoniae Decoction restores intestinal barrier dysfunction by promoting the interaction between ILC3 and gut flora.

BACKGROUND: Intestinal barrier dysfunction is a significant contributor to the recurrence and refractory of ulcerative colitis (UC). Promoting the interaction between group 3 innate lymphoid cells (ILC3s) and gut flora is a valuable strategy for mucosal repair. Paeoniae decoction (PD) is a compound commonly used in clinical treatment of UC, but its exact mechanism remains unclear. PURPOSE: We aimed to investigate the protective effect of PD on intestinal mucosal injury induced by dextran sulfate sodium (DSS) in chronic colitis, as well as to elucidate its potential mechanism. METHODS: C57BL/6 mice were induced with chronic colitis by 2 % DSS and divided into four groups: control group, model group, PD low dose (4 g/kg), and high dose (8 g/kg) group. The effectiveness of PD in treating chronic colitis mice was evaluated based on changes in body weight, colon length, colon pathological tissue scores, and the mRNA levels of inflammatory factors IL-6 and IL-1ß. The expressions of intestinal epithelial tight junction proteins (ZO-1 and Occludin), IL-22, and MUC2 were observed using immunofluorescence and RT-PCR. Additionally, the proportion of ILC3 and natural cytotoxicity receptor (NCR)+ ILC3 in the colon were detected using flow cytometry. Furthermore, UHPLC-QE-MS was utilized to identify chemical components of PD and network pharmacology was employed to predict potential pathways for PD intervention in UC. Subsequently, MNK-3 cells (ILC3 in vitro cell line) and NCM460 cells were used to verify the network pharmacology results. Finally, the effects of PD on UC gut flora have been explored using in vitro fermentation and 16S rDNA techniques. RESULTS: The results showed that PD significantly restored body weight and colon length in mice with chronic colitis, while also reducing colon inflammatory cell infiltration and the expression of IL-6 and IL-1ß. Additionally, PD notably promoted the expression of MUC2, ZO-1, Occludin, and IL-22, as well as increasing the ratio of ILC3 and NCR+ILC3. UHPLC-QE-MS analysis identified 443 components of PD, and network pharmacology suggested that PD could target the aryl hydrocarbon receptor (AHR) signaling pathway, which was confirmed by MNK-3 cells and in vitro fermentation experiments. Furthermore, MNK-3-conditioned medium (CM) increased the expression of ZO-1 and Occludin in NCM460 cells. In addition, 16S rDNA results indicated that PD promoted the abundance of Lactobacillales, thus contributing to mucosal damage repair by activating the AHR signal in ILC3s. CONCLUSION: In summary, our study demonstrates that PD repairs intestinal mucosal damage in chronic colitis by regulating the interaction of gut flora with ILC3, and the specific mechanism is related to the activation of AHR signaling pathway.

Paeoniflorin ameliorates chronic colitis via the DR3 signaling pathway in group 3 innate lymphoid cells.

Inhibiting the death receptor 3 (DR3) signaling pathway in group 3 innate lymphoid cells (ILC3s) presents a promising approach for promoting mucosal repair in individuals with ulcerative colitis (UC). Paeoniflorin, a prominent component of Paeonia lactiflora Pall., has demonstrated the ability to restore barrier function in UC mice, but the precise mechanism remains unclear. In this study, we aimed to delve into whether paeoniflorin may promote intestinal mucosal repair in chronic colitis by inhibiting DR3 signaling in ILC3s. C57BL/6 mice were subjected to random allocation into 7 distinct groups, namely the control group, the 2 % dextran sodium sulfate (DSS) group, the paeoniflorin groups (25, 50, and 100 mg/kg), the anti-tumor necrosis factor-like ligand 1A (anti-TL1A) antibody group, and the IgG group. We detected the expression of DR3 signaling pathway proteins and the proportion of ILC3s in the mouse colon using Western blot and flow cytometry, respectively. Meanwhile, DR3-overexpressing MNK-3 cells and 2 % DSS-induced Rag1-/- mice were used for verification. The results showed that paeoniflorin alleviated DSS-induced chronic colitis and repaired the intestinal mucosal barrier. Simultaneously, paeoniflorin inhibited the DR3 signaling pathway in ILC3s and regulated the content of cytokines (Interleukin-17A, Granulocyte-macrophage colony stimulating factor, and Interleukin-22). Alternatively, paeoniflorin directly inhibited the DR3 signaling pathway in ILC3s to repair mucosal damage independently of the adaptive immune system. We additionally confirmed that paeoniflorin-conditioned medium (CM) restored the expression of tight junctions in Caco-2 cells via coculture. In conclusion, paeoniflorin ameliorates chronic colitis by enhancing the intestinal barrier in an ILC3-dependent manner, and its mechanism is associated with the inhibition of the DR3 signaling pathway.

Wogonin improves colitis by activating the AhR pathway to regulate the plasticity of ILC3/ILC1.

BACKGROUND: Intestinal barrier dysfunction caused by the disrupted balance of group 3 innate lymphoid cells (ILC3)/group 1 innate lymphoid cells (ILC1) is a significant feature in the pathogenesis of inflammatory bowel disease (IBD). Activation of aryl hydrocarbon receptor (AhR) signaling contributes to the maintenance of ILC3/ILC1 balance. Wogonin, a natural flavonoid from Scutellaria baicalensis Georgi, can repair intestinal mucosal damage of IBD. However, it remains unclear if wogonin can exert a therapeutic effect by activating the AhR pathway to regulate the plasticity of ILC3/ILC1. PURPOSE: In this study, we investigated the immunomodulatory effects of wogonin on IBD and its potential mechanisms in vitro and in vivo. STUDY DESIGN AND METHODS: Chronic colitis was induced by four cycles of 2 % DSS treatment in mice. 20 mg kg-1/day wogonin was administrated by oral gavage and mice were treated intraperitoneally with 10 mg kg-1/2 days CH223191 to block the AhR pathway. Colon tissues were processed for histopathological examination and evaluation of the epithelial barrier function by immunohistochemistry. The activation of the AhR pathway and the plasticity of ILC3/ILC1 were determined by western blot and flow cytometry. Then, we also detected the intestinal microflora and their metabolites by 16 s sequencing and non-targeted Metabolomics analysis. Furthermore, an in vitro culture system consisting of MNK3 cells and NCM460 cells, and a CETSA assay were performed to confirm the molecular mechanism. RESULTS: Wogonin ameliorated histological severity of the colon, decreased the secretion of inflammatory factors, and increased tight junction proteins in colitis mice. These effects are associated with the tendency of conversion from ILC3 to ILC1 prevented by wogonin, which was offset by AhR antagonist CH223191. In addition, wogonin exerted the curative effect by altering gut microbiota to produce metabolites such as Kynurenic acid, and 1H-Indole-3-carboxaldehyde as AhR endogenous ligands. In vitro data further verified that wogonin as an exogenous ligand directly binds to the structural domain of AhR by CETSA. Also, the supernatant of MNK-3 cells stimulated with wogonin enhanced expression of Occludin and Claudin1 in NCM460 cells induced by LPS. CONCLUSION: Cumulatively, our study illustrated that wogonin improved the outcomes of DSS-induced chronic colitis via regulating the plasticity of ILC3/ILC1. Its specific mechanism is to binding to AhR directly, and to activate the AhR pathway indirectly by altering the tryptophan metabolisms of gut microbiota.

Quercetin ameliorates ulcerative colitis by activating aryl hydrocarbon receptor to improve intestinal barrier integrity.

Ulcerative colitis (UC) pathogenesis is largely associated with intestinal epithelial barrier dysfunction. A therapeutic approach to UC involves the repair of damaged intestinal barrier. Our study aimed to investigate whether aryl hydrocarbon receptor (AhR) mediated the intestinal barrier repair effects of quercetin to ameliorate UC. 3% dextran sulfate sodium was used to induce colitic mice, and quercetin (25, 50, and 100 mg/kg) was administered orally for 10 days to assess the therapeutic effects. In vitro, Caco-2 cells were used to explore the effect of quercetin on tight junction protein expression and AhR activation. The results showed that quercetin alleviated colitic mice by restoring tight junctions (TJs) integrity via an AhR-dependent manner (p < 0.05). In vitro, quercetin dose-dependently elevated the expressions of TJs protein ZO-1 and Claudin1, and activated AhR by enhancing the expression of CYP1A1 and facilitating AhR nuclear translocation in Caco-2 cells (p < 0.05). While AhR antagonist CH223191 reversed the therapeutic effects of quercetin (p < 0.05) and blocked quercetin-induced AhR activation and enhancement of TJs protein (p < 0.05). In conclusion, quercetin repaired intestinal barrier dysfunction by activating AhR-mediated enhancement of TJs to alleviate UC. Our research offered new perspectives on how quercetin enhanced intestinal barrier function.

Sentiment analysis algorithm using contrastive learning and adversarial training for POI recommendation.

Finding a suitable POI based on the user's needs and intentions is a complex decision-making process. Obtaining valuable information from the vast amount of social media data and using it for travel recommendations is a challenging issue. Traditional POI recommendation algorithms do not fully take into account the true feelings of customers about tourist attractions implied in social media data because they usually require a large amount of tagged travel commentary data. This study presents an aspect-based sentiment analysis model and POI recommendation method to accurately capture sentiment information contained in social media data with a small amount of tagged data. The pre-training model BERT is used to obtain the embedded representation of words that fuse the semantic information of the text. Using contrastive learning, point clusters belonging to the same class in the embedded space of words are pulled together, and sample clusters from different classes are separated. The potential relationship between comment ratings and their impact on user perception is analyzed, and the best performance formula for the loss function is determined. The test accuracy and F1-Score of the model in the experiment improved by 13.03% and 12.23%, respectively, compared to the BERT base model. POI recommendation validation is performed using a variety of recommendation algorithms. The experimental results show that the addition of aspect-based sentiment attributes can effectively improve the accuracy of recommendations.

Phylotranscriptomics and evolution of key genes for terpene biosynthesis in Pinaceae.

Pinaceae is the largest family of conifers, dominating forest ecosystems and serving as the backbone of northern, temperate and mountain forests. The terpenoid metabolism of conifers is responsive to pests, diseases, and environmental stress. Determining the phylogeny and evolution of terpene synthase genes in Pinaceae may shed light on early adaptive evolution. We used different inference methods and datasets to reconstruct the Pinaceae phylogeny based on our assembled transcriptomes. We identified the final species tree of Pinaceae by comparing and summarizing different phylogenetic trees. The genes encoding terpene synthase (TPS) and cytochrome P450 proteins in Pinaceae showed a trend of expansion compared with those in Cycas. Gene family analysis revealed that the number of TPS genes decreased while the number of P450 genes increased in loblolly pine. Expression profiles showed that TPSs and P450s were mainly expressed in leaf buds and needles, which may be the result of long-term evolution to protect these two vulnerable tissues. Our research provides insights into the phylogeny and evolution of terpene synthase genes in Pinaceae and offers some useful references for the investigation of terpenoids in conifers.

An Investigation of All Fiber Free-Running Dual-Comb Spectroscopy.

A dual-comb spectroscopy (DCS) system uses two phase-locked optical frequency combs with a slight difference in the repetition frequency. The spectrum can be sampled in the optical frequency (OF) domain and reproduces the characteristics in the radio frequency (RF) domain through asynchronous optical sampling. Therefore, the DCS system shows great advantages in achieving precision spectral measurement. During application, the question of how to reserve the mutual coherence between the two combs is the key issue affecting the application of the DCS system. This paper focuses on a software algorithm used to realize the mutual coherence of the two combs. Therefore, a pair of free-running large anomalous dispersion fiber combs, with a center wavelength of approximately 1064 nm, was used. After the signal process, the absorption spectra of multiple species were simultaneously obtained (simulated using the reflective spectra of narrow-bandwidth fiber Bragg gratings, abbreviated as FBG). The signal-to-noise ratio (SNR) could reach 13.97 dB (25) during the 100 ms sampling time. In this study, the feasibility of the system was first verified through the simulation system; then, a principal demonstration experiment was successfully executed. The whole system was connected by the optical fiber without additional phase-locking equipment, showing promise as a potential solution for the low-cost and practical application of DCS systems.

Wogonin regulates colonocyte metabolism via PPARγ to inhibit Enterobacteriaceae against dextran sulfate sodium-induced colitis in mice.

To investigate the potential effects and mechanism of wogonin on dextran sulfate sodium (DSS)-induced colitis, 70 male mice were administered wogonin (12.5, 25, 50 mg·kg-1 ·d-1 , i.g.) for 10 days, meanwhile, in order to induce colitis, the mice were free to drink 3% DSS for 6 days. We found that wogonin could obviously ameliorate DSS-induced colitis, including preventing colon shortening and inhibiting pathological damage. In addition, wogonin could increase the expression of PPARγ, which not only restores intestinal epithelial hypoxia but also inhibits iNOS protein to reduce intestinal nitrite levels. All these effects facilitated a reduction in the abundance of Enterobacteriaceae in DSS-induced colitis mice. Therefore, compared with the DSS group, the number of Enterobacteriaceae in the intestinal flora was significantly reduced after administration of wogonin or rosiglitazone by 16s rDNA technology. We also verified that wogonin could promote the expression of PPARγ mRNA and protein in Caco-2 cells, and this effect disappeared when PPARγ signal was inhibited. In conclusion, our study suggested that wogonin can activate the PPARγ signal of the Intestinal epithelium to ameliorate the Intestinal inflammation caused by Enterobacteriaceae bacteria expansion.

Gegen Qinlian decoction activates AhR/IL-22 to repair intestinal barrier by modulating gut microbiota-related tryptophan metabolism in ulcerative colitis mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Gegen Qinlian decoction (GQD) is a traditional Chinese medicine derived from Treatise on febrile diseases and is clinically used for the treatment of acute ulcerative colitis (UC). However, the potential mechanism of GQD treatment for UC remains elusive. AIM OF STUDY: In this study, we aimed to explore the involvement of gut microbiota-related tryptophan metabolism in mediating protective effects of GQD against intestinal barrier damage. MATERIALS AND METHODS: Mice with colitis were treated with 3% dextran sulfate sodium (DSS) for 6 days. The therapeutic effects of GQD in UC mice were examined based on body weight, disease activity index (DAI), organ index, length and pathological changes in the colon. The distribution of fluorescein isothiocyanate dextran (FITC-dextran) in the intestinal tract was observed using small animal imaging, while concentration of FITC-dextran in serum was detected using a fluorescein microplate analyser. Bacterial infiltration in colon tissues was observed by fluorescence in situ hybridisation (FISH), and the bacterial load in mesenteric lymph nodes (MLNs) was further examined through bacterial culture. Subsequently, colonic goblet cells were detected using Alcian blue staining. The tight junctions of the colonic epithelium were observed using transmission electron microscopy, and the expression of tight junction proteins was detected by immunofluorescence (IF) and western blot. In addition, flow cytometry was used to analyse the proportion of interleukin-22-positive (IL-22+) ILC3 cells in lamina propria lymphocytes, and the content of IL-22 in colon homogenates was determined using an ELISA kit. In addition, targeted tryptophan metabolomics was used to detect the concentration of indole derivatives produced by tryptophan metabolism in faeces, and 16S rDNA was used to investigate the composition and abundance of gut microbiota-related tryptophan metabolism. RESULTS: Administration of GQD significantly alleviated the pathological symptoms, including weight loss, increased DAI score, changes in organ index, colon shortening, and colon pathological injury in UC mice. In addition, GQD reduced the diffusion of FITC-dextran in the intestinal tract, the content of FITC-dextran in serum, and bacterial infiltration in MLNs and colon tissues. Additionally, GQD significantly increased the number of colonic goblet cells, repaired the structure of epithelial tight junctions and increased the expression of tight junction proteins. Furthermore, GQD significantly increased the proportion of IL-22+ ILC3 in the lamina propria, the expression of CYP1A1 protein in colon tissue, and the level of IL-22 in colon homogenates. However, the above protective effects of GQD were inhibited by co-administration of GQD and aryl hydrocarbon receptor (AhR) antagonist. Additionally, GQD restored the content of indole derivatives generated by tryptophan metabolism, regulated the diversity of the gut microbiota, and significantly increased the abundance of genes related to tryptophan metabolism. CONCLUSION: Our results confirmed that GQD repaired the damaged intestinal barrier in UC mice by regulating gut microbiota-related tryptophan metabolism and restoring the generation of indole derivatives to activate AhR-mediated IL-22 production.

Luteolin alleviates ulcerative colitis by restoring the balance of NCR-ILC3/NCR+ILC3 to repairing impaired intestinal barrier.

Ulcerative colitis (UC) is a multifactorial, refractory chronic inflammatory disease. The primary factor leading to prolonged ulcerative colitis is the imbalance of the group 3 innate lymphoid cells (ILC3) subgroup resulting in the delayed reconstruction of damaged intestinal barrier. Previous studies show that luteolin had efficacy on UC, however, the potency of luteolin on restoring the balance of NCR-ILC3/NCR+ILC3 to repairing impaired intestinal barrier remains unclear. In this study, to investigate the potential mechanism of luteolin on ILC3 subgroup, we first evidenced that luteolin could promote transformation NCR-MNK3 to NCR+MNK3 in vitro. Then, a UC model was established in C57BL/6J mice to assess the efficacy of luteolin in restoring ILC3 subgroup balance and repairing intestinal barrier in chronic UC. Finally, the experiments in vitro validated the potential mechanism of luteolin in regulating ILC3 plasticity. The results showed that luteolin significantly alleviated the symptoms of DSS-induced UC in mice, including preventing body weight loss and decreasing the disease activity index (DAI) and intestinal damages. Additionally, luteolin increased NCR+ILC3 levels, promoted the production of IL-22 and decreased the levels of IL-17a and INF-γ in the intestine, and encourage intestinal barrier function recovery in UC mice by promoting the expression of ZO-1 and Occludin. Experiments in vitro revealed that luteolin facilitated the transformation of NCR-MNK3 to NCR+MNK3 and promoted the secretion of IL-22, which was linked to the Notch pathway. All results revealed that luteolin restored the balance of NCR-ILC3/NCR+ILC3 and contributed to repair of injured intestinal epithelium to alleviate ulcerative colitis.

Dahuang Mudan decoction repairs intestinal barrier in chronic colitic mice by regulating the function of ILC3.

ETHNOPHARMACOLOGICAL RELEVANCE: Dahuang Mudan decoction (DMD) is a classic prescription for treating intestinal carbuncle from Zhang Zhongjing's "Essentials of the Golden Chamber" in the Han Dynasty. Recent studies also prove that DMD has a therapeutic effect on ulcerative colitis (UC), but its mechanism is still unclear. AIM OF STUDY: In this study, we aim to assess the therapeutic effect of DMD on DSS-induced chronic colitis in mice and deeply expound its underlying regulative mechanism. MATERIALS AND METHODS: The efficacy of DMD on mice with 2% DSS-induced chronic colitis was examined by changes in mouse body weight, DAI score, colon length changes, peripheral blood white blood cells (WBC) and red blood cells (RBC) counts, and hemoglobin (HGB) content, using mesalazine as a positive control. A small animal imaging system observed the FITC-Dextran fluorescence distribution in mice, and the contents of IL-22 and IL-17A in colon tissue homogenate supernatant and LPS in peripheral blood were detected by ELISA. Fluorescence in situ molecular hybridization and bacterial culture were used to investigate bacterial infiltration in intestinal mucosa and bacterial translocation in mesenteric lymph nodes and spleen. Mice immune function was further evaluated by analyzing the changes in spleen index, thymus index, and the ratio of peripheral blood granulocytes, monocytes, and lymphocytes. Meanwhile, the proportion of NCR+ group 3 innate lymphoid cells (ILC3), NCR-ILC3, and IL-22+ILC3 in colonic lamina propria lymphocytes of mice was detected by flow cytometry. The contents of effectors IL-22, IL-17A, and GM-CSF were detected by RT-PCR. We use cell scratching to determine the effect of DMD conditioned medium on the migration of Caco-2 cells by establishing an in vitro model of MNK-3 conditioned medium (CM) intervening Caco-2 cells. RT-PCR and WB detect the expression of tight junction ZO-1, Occludin, and Claudin-1. RESULTS: DMD restored the body weight, colon length, peripheral blood RBC numbers, and HGB content of chronic colitis mice and reduced peripheral blood WBC and colon inflammatory cell infiltration. Moreover, DMD decreased LPS content in serum, bacterial infiltration of colonic mucosa, and bacterial translocation in spleen and mesenteric lymph nodes. Simultaneously, DMD intensified the expression of ZO-1, Occludin, and Claudin-1, the ratio of NCR+ILC3 and IL-22+ILC3, and decreased the proportion of NCR-ILC3. In vitro studies also confirmed that the conditioned medium of DMD promoted the migration of Caco-2 cells and the expression of tight junction proteins. CONCLUSION: Our results confirm that DMD improves inflammation and restores intestinal epithelial function in mice with chronic colitis, and the mechanism may be related to regulating ILC3 function.

Emodin targeting the colonic metabolism via PPARγ alleviates UC by inhibiting facultative anaerobe.

BACKGROUND: Emodin is an active ingredient of traditional Chinese medicine Rheum palmatum L. and Polygonum cuspidatum, which possesses anti-inflammatory and intestinal mucosal protection effects. Our previous study found that emodin significantly alleviated ulcerative colitis induced by sodium dextran sulfate (DSS). In this study, we found the underlying mechanism of emodin on ulcerative colitis (UC). PURPOSE: We aimed to further explore the mechanism of emodin in the treatment of ulcerative colitis from the perspective of metabolism and intestinal flora. METHODS: Ulcerative colitis was induced by 3% sodium dextran sulfate (DSS) on mice, and the mice were respectively treated with mesalazine, rosiglitazone, emodin, and emodin combined with GW9662 (PPARγ inhibitor) simultaneously. Weight changes, the disease activity index (DAI), colonic length, and pathologic changes in colon were used to evaluate the efficacy of emodin. LC-MS/MS was performed for metabolomics analysis of colon. In addition, intestinal flora was assessed using 16S rDNA sequencing. A vector-based short hairpin RNA (shRNA) method was used to silence PPARγ gene expression in Caco-2 cells. RESULTS: Emodin binds to the active site of PPARγ protein and forms hydrogen bond interaction with ARG288 and CYS285 amino acids. Furthermore, Emodin significantly promotes the protein expression of PPARγ, while inhibiting iNOS and NF-kB p65 in UC mice, however, this effect is hardly shown when it is combined with GW9662 (the inhibitor of PPARγ). Meanwhile, emodin suppresses the expression of iNOS in Caco-2 cells induced with IFNγ and IL-22, but has no effect on its expression in shPPARγ-Caco-2 cells. In addition, through activating PPARγ signal pathway, emodin is capable of regulating colonic metabolism including oxidative phosphorylation and citrulline metabolism and effecting luminal availability of oxygen and nitrate. This promotes the recovery of anoxic environment of colon epithelial cells, which strains the growth and expansion of Enterobacteriaceae. CONCLUSION: The mechanism of Emodin in the treatment of ulcerative colitis relies on its regulation of PPARγ signal pathway, which could modulate colonic metabolism and restore intestinal homeostasis.

Positive Association Between Fluoroquinolone Exposure and Tendon Disorders: A Nationwide Population-Based Cohort Study in Taiwan.

Introduction: Fluoroquinolone exposure is reportedly associated with a higher risk of tendon disorders, tendonitis, or tendon rupture. However, studies in East Asian populations have not confirmed these risks in patients with comorbidities or concomitant medication use. This cohort study was designed to investigate the associations among fluoroquinolone exposure, comorbidities, medication use, and tendon disorders in Taiwan. Materials and Methods: This population-based, nationwide, observational, cohort study used data from the National Health Insurance Research database in Taiwan, a nationwide claims database that covers more than 99% of the Taiwanese population. The study period was from January 2000 to December 2015, and the median follow-up time was 11.05 ± 10.91 years. Patients who were exposed to fluoroquinolones for more than three consecutive days were enrolled, and patients without fluoroquinolone exposure who were matched by age, sex, and index year were enrolled as controls. The associations of comorbidities and concomitant medication use with tendon disorder occurrence were analyzed using Cox regression models. Results: The incidence of tendon disorders were 6.61 and 3.34 per 105 person-years in patients with and without fluoroquinolone exposure, respectively (adjusted hazard ratio, 1.423; 95% confidence interval [1.02,1.87]; p = 0.021). Sensitivity analyses yielded similar results. Patients under 18 and over 60 years with fluoroquinolone exposure; those with chronic kidney disease, diabetes, rheumatologic disease, cardiac disease, lipid disorder, or obesity; and those who concomitantly used statins, aromatase inhibitors, or glucocorticoids, had a significantly higher risk of tendon disorders. Conclusion: The long-term risk of tendon disorders was higher in patients with fluoroquinolone exposure than in those without fluoroquinolone exposure. Clinicians should assess the benefits and risks of fluoroquinolone use in patients at high risk of tendon disorders who require fluoroquinolone administration.

New insights into precocious puberty and ADHD: a nationwide cohort study.

BACKGROUND: Attention deficit-hyperactivity disorder (ADHD) is one of the most common neurodevelopmental disorders in children; however, studies delineating the association between ADHD and central precocious puberty are limited. This study aimed to understand whether children with ADHD are at a higher risk of central precocious puberty. METHODS: This population-based retrospective cohort study was conducted using the National Health Insurance Research Database of Taiwan to investigate the association between ADHD and the incidence of central precocious puberty between 2000-2015. We identified ADHD individuals treated with methylphenidate, atomoxetine or not. The control cohort consisted of individuals without ADHD. The outcome measure was central precocious puberty diagnosis. RESULTS: Among 290,148 children (mean age: 5.83 years), central precocious puberty incidence was 4.24 and 1.95 per 105 person-years in the ADHD and control groups, respectively. Children with ADHD treated with medication had a higher risk than those without ADHD. However, medication use did not affect the incidence of central precocious puberty among children with ADHD. CONCLUSION: This study showed an association between ADHD and a higher risk of central precocious puberty. Early referral of children with ADHD to a pediatric endocrinologist for evaluation may facilitate correct diagnoses and early interventions. IMPACT: ADHD is associated with a higher risk of central precocious puberty. This study provides relevant findings, as it is the first nationwide, population-based cohort study to investigate the association between ADHD and the risk of central precocious puberty with a 15-year follow-up. Early referral of children with ADHD to a pediatric endocrinologist for the evaluation of suspected precocious puberty could facilitate correct diagnosis. Early intervention treatment with gonadotropin-releasing hormone agonist might improve final height in children with central precocious puberty.

Factors Influencing the Reputation of Assistive Technology Resources Center: An Example from Yunlin County, Taiwan.

By the end of 2020, a total of 34 multifunctional Assistive Technology Resources Centers (ATR centers) were set up in 22 counties and cities in Taiwan. This study examines the perceptions of the users and their caregivers of the government-established ATR centers in Taiwan and examines the impact on the reputation of the public institution. The research framework and hypotheses were developed by examining the factors of "service convenience", "center-related factors", "justice", and "perceived value" and using "perceived value" as a mediating variable. The data were collected through a questionnaire survey, and the structural equation model was used to test the model and verify the hypotheses. Research data was collected in various townships in Yunlin County A total of 320 questionnaires were collected. Of these respondents, 22% were aged 51-60. All the research hypotheses were positively and significantly verified. Of these, justice was the most important factor affecting the value of the ATR center's services compared to convenience and center-related factors. Of convenience, service value and justice, service value was the most important factor affecting the perceived reputation of the public institution. According to the findings of this study, it is beyond expectation that the convenience of ATR is not the main factor influencing the service value, but rather the perceived justice is the most important factor. Therefore, ATR should be prioritized from the perspective of the service recipient, especially the perceived justice of the service, in order to best enhance the value of the service and improve the reputation of the public institution.

Effect of Huangqin decoction on regulating intestinal flora in colitis mice characterized as inhibition of the NOD2-dependent pathway.

CONTEXT: Chinese herb Huangqin decoction (HQD) can regulate intestinal flora in ulcerative colitis (UC) mice. OBJECTIVE: Our study clarifies the mechanism of HQD in regulating the intestinal flora of UC mice. MATERIALS AND METHODS: Male C57BL/6 mice were randomly divided into six groups: Control, Model (3% DSS), Sulfasalazine (500 mg/kg), HQD-L (250 mg/kg), HQD-M (500 mg/kg), and HQD-H (1000 mg/kg) groups. Measurement of body weight, colon length, DAI, and haematoxylin-eosin staining were conducted. FISH and 16S rDNA detected colonic bacterial infiltration and intestinal flora changes. The expression of RegIIIγ and PRRs (NOD2, TLR5, TLR4) were detected by FCM and WB, respectively. In addition, WB, qPCR, or IHC were used to detect the expression of NOD2, MyD88, RIP2, and NF-κB p65 in the colon. ELISA was used to determine cytokines. RESULTS: Compared with the model group (DAI score, 2.38 ± 0.05; histological score, 4.08 ± 0.54), HQD treatment significantly reduced the DAI score (L, 2.16 ± 0.09; M, 1.45 ± 0.05; H, 1.18 ± 0.05) and histological score (L, 3.16 ± 0.82; M, 2.50 ± 0.81; H, 1.51 ± 0.76); restored the weight, the colonic length (p < 0.05). 16S rDNA identification showed HQD regulated the balance of intestinal flora. Moreover, HQD suppressed the expression of RegIIIγ (p < 0.05) and prevented colonic bacterial infiltration. Furthermore, WB results showed NOD2, and TLR4 were inhibited by HQD, especially NOD2 (p < 0.01). The data of WB, qPCR, and IHC demonstrated that the NOD2-dependent pathway was inhibited by HQD (p < 0.01). DISCUSSION AND CONCLUSIONS: HQD (1000 mg/kg) regulates the intestinal flora of colitis mice, mainly characterized as inhibition of the NOD2-dependent pathway. These results indicate that HQD has potential.

Implantation of monocusp valve prolongs the duration of chest tube drainage in children with tetralogy of fallot after corrective surgery.

BACKGROUND: Right ventricular outflow tract obstruction relief is one of the major procedures during the total correction of tetralogy of Fallot (TOF). Pulmonary insufficiency (PI) is usually inevitable after a transannular incision with a patch repair is performed. Therefore, some surgeons advocate to place a monocusp valve within the transannular patch (TAP) in order to decrease the severity of the PI. However, the monocusp valve seemed not be very effective in some patients who underwent the complete TOF repair. METHODS: Patients who had the classic form of TOF between January 2009 and January 2017 and underwent the corrective surgery with a TAP by the same cardiovascular surgeon were identified for further analysis. Clinical information including demographics at operation, perioperative data, and postoperative outcome were collected retrospectively and compared between the group with and without a monocusp valve. RESULTS: A total of 24 TOF cases were included in the final analysis, and 16 (66.7%) patients received a monocusp valve placement. The patients' characteristics before and during the surgery were similar between the two groups. The median duration of chest tube drainage after the total correction in the monocusp group was longer than those without the valve (p = 0.04). There was no difference in the immediate postoperative data, including the inflammation/infection status, the duration of mechanical ventilation, and the length of ICU and hospital stay. CONCLUSION: Implantation of a monocusp valve during the total TOF correction using a TAP did not bring benefit to improve the immediate postoperative outcomes, especially the duration of the pleural drainage. Further study with a prospective design and a larger number of cases is needed.

Baicalein ameliorates ulcerative colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s.

Ulcerative colitis (UC) is a chronic inflammatory disease of the gastrointestinal tract, which is closely related to gut barrier dysfunction. Emerging evidence shows that interleukin-22 (IL-22) derived from group 3 innate lymphoid cells (ILC3s) confers benefits on intestinal barrier, and IL-22 expression is controlled by aryl hydrocarbon receptor (AhR). Previous studies show that baicalein protects the colon from inflammatory damage. In this study we elucidated the molecular mechanisms underlying the protective effect of baicalein on intestinal barrier function in colitis mice. Mice were administered baicalein (10, 20, 40 mg·kg-1·d-1, i.g.) for 10 days; the mice freely drank 3% dextran sulfate sodium (DSS) on D1-D7 to induce colitis. We showed that baicalein administration simultaneously ameliorated gut inflammation, decreased intestinal permeability, restored tight junctions of colons possibly via promoting AhR/IL-22 pathway. Co-administration of AhR antagonist CH223191 (10 mg/kg, i.p.) partially blocked the therapeutic effects of baicalein in colitis mice, whereas AhR agonist FICZ (1 µg, i.p.) ameliorated symptoms and gut barrier function in colitis mice. In a murine lymphocyte line MNK-3, baicalein (5-20 µM) dose-dependently increased the expression of AhR downstream target protein CYP1A1, and enhanced IL-22 production through facilitating AhR nuclear translocation, these effects were greatly diminished in shAhR-MNK3 cells, suggesting that baicalein induced IL-22 production in AhR-dependent manner. To further clarify that, we constructed an in vitro system consisting of MNK-3 and Caco-2 cells, in which MNK-3 cell supernatant treated with baicalein could decrease FITC-dextran permeability and promoted the expression of tight junction proteins ZO-1 and occluding in Caco-2 cells. In conclusion, this study demonstrates that baicalein ameliorates colitis by improving intestinal epithelial barrier via AhR/IL-22 pathway in ILC3s, thus providing a potential therapy for UC.

Integrated Analysis of the Transcriptome and Metabolome Reveals Genes Involved in Terpenoid and Flavonoid Biosynthesis in the Loblolly Pine (Pinus taeda L.).

Loblolly pine (Pinus taeda L.) is an important tree for afforestation with substantial economic and ecological value. Many metabolites with pharmacological activities are present in the tissues of P. taeda. However, the biosynthesis regulatory mechanisms of these metabolites are poorly understood. In the present study, transcriptome and metabolome analyses were performed on five tissues of P. taeda. A total of 40.4 million clean reads were obtained and assembled into 108,663 unigenes. These were compared with five databases, revealing 39,576 annotated unigenes. A total of 13,491 differentially expressed genes (DEGs) were observed in 10 comparison groups. Of these, 487 unigenes exhibited significantly different expressions in specific tissues of P. taeda. The DEGs were explored using Gene Ontology and Kyoto Encyclopedia of Genes and Genomes metabolic pathway analysis. We identified 343 and 173 candidate unigenes related to the biosynthesis of terpenoids and flavonoids, respectively. These included 62 R2R3-MYB, 30 MYB, 15 WRKY, seven bHLH, seven ERF, six ZIP, five AP2, and one WD40 genes that acted as regulators in flavonoid and/or terpenoid biosynthesis. Additionally, metabolomics analysis detected 528 metabolites, among which 168 were flavonoids. A total of 493 differentially accumulated metabolites (DAMs) were obtained in 10 comparison groups. The 3,7-Di-O-methyl quercetin was differentially accumulated in all the comparison groups. The combined transcriptome and metabolome analyses revealed 219 DEGs that were significantly correlated with 45 DAMs. Our study provides valuable genomic and metabolome information for understanding P. taeda at the molecular level, providing a foundation for the further development of P. taeda-related pharmaceutical industry.