An atlas of the tomato epigenome reveals that KRYPTONITE shapes TAD-like boundaries through the control of H3K9ac distribution.

In recent years, the exploration of genome three-dimensional (3D) conformation has yielded profound insights into the regulation of gene expression and cellular functions in both animals and plants. While animals exhibit a characteristic genome topology defined by topologically associating domains (TADs), plants display similar features with a more diverse conformation across species. Employing advanced high-throughput sequencing and microscopy techniques, we investigated the landscape of 26 histone modifications and RNA polymerase II distribution in tomato (Solanum lycopersicum). Our study unveiled a rich and nuanced epigenetic landscape, shedding light on distinct chromatin states associated with heterochromatin formation and gene silencing. Moreover, we elucidated the intricate interplay between these chromatin states and the overall topology of the genome. Employing a genetic approach, we delved into the role of the histone modification H3K9ac in genome topology. Notably, our investigation revealed that the ectopic deposition of this chromatin mark triggered a reorganization of the 3D chromatin structure, defining different TAD-like borders. Our work emphasizes the critical role of H3K9ac in shaping the topology of the tomato genome, providing valuable insights into the epigenetic landscape of this agriculturally significant crop species.

BRAD V3.0: an upgraded Brassicaceae database.

The Brassicaceae Database (BRAD version 3.0, BRAD V3.0; http://brassicadb.cn) has evolved from the former Brassica Database (BRAD V2.0), and represents an important community portal hosting genome information for multiple Brassica and related Brassicaceae plant species. Since the last update in 2015, the complex genomes of numerous Brassicaceae species have been decoded, accompanied by many omics datasets. To provide an up-to-date service, we report here a major upgrade of the portal. The Model-View-ViewModel (MVVM) framework of BRAD has been re-engineered to enable easy and sustainable maintenance of the database. The collection of genomes has been increased to 26 species, along with optimization of the user interface. Features of the previous version have been retained, with additional new tools for exploring syntenic genes, gene expression and variation data. In the 'Syntenic Gene @ Subgenome' module, we added features to view the sequence alignment and phylogenetic relationships of syntenic genes. New modules include 'MicroSynteny' for viewing synteny of selected fragment pairs, and 'Polymorph' for retrieval of variation data. The updated BRAD provides a substantial expansion of genomic data and a comprehensive improvement of the service available to the Brassicaceae research community.

Aspirin loaded extracellular vesicles inhibit inflammation of macrophages via switching metabolic phenotype in periodontitis.

OBJECTIVES: Changes of macrophage in the local immune microenvironment of periodontitis cause alveolar bone resorption. This study aims to investigate the effect of a new drug delivery method of aspirin on the immune microenvironment of periodontitis to promote alveolar bone repair, and to explore mechanism of aspirin's effect on macrophage. METHODS: We isolated extracellular vesicles (EVs) from periodontal stem cells (PDLSCs) and loaded with aspirin by sonication, and then evaluated the treatment efficacy of aspirin-loaded vesicles (EVs-ASP) in periodontitis model in mice. In vitro, we explored the role of EVs-ASP in the regulation of LPS-induced macrophages. The underlying mechanism by which EVs-ASP regulates phenotypic remodeling of macrophages in periodontitis was further investigated. RESULTS: EVs-ASP inhibited the inflammatory environment of LPS-induced macrophage, and promoted anti-inflammatory macrophages formation both in vivo and in vitro, and reduced bone loss in periodontitis models. Moreover, EVs-ASP enhanced oxidative phosphorylation and suppressed glycolysis in macrophages. CONCLUSIONS: Consequently, EVs-ASP improves the periodontal immune microenvironment by enhancing oxidative phosphorylation (OXPHOS) in macrophages, resulting in a certain degree of regeneration of alveolar bone height. Our study provides a new potential strategy for bone repair in periodontitis therapy.

Differences between physician and patient preferences for cancer treatments: a systematic review.

BACKGROUND: Shared decision-making is useful to facilitate cancer treatment decisions. However, it is difficult to make treatment decisions when physician and patient preferences are different. This review aimed to summarize and compare the preferences for cancer treatments between physicians and patients. METHODS: A systematic literature search was conducted on PubMed, Embase, PsycINFO, CINAHL and Scopus. Studies elicited and compared preferences for cancer treatments between physicians and patients were included. Information about the study design and preference measuring attributes or questions were extracted. The available relative rank of every attribute in discrete choice experiment (DCE) studies and answers to preference measuring questions in non-DCE studies were summarized followed by a narrative synthesis to reflect the preference differences. RESULTS: Of 12,959 studies identified, 8290 were included in the title and abstract screening and 48 were included in the full text screening. Included 37 studies measured the preferences from six treatment-related aspects: health benefit, adverse effects, treatment process, cost, impact on quality of life, and provider qualification. The trade-off between health benefit and adverse effects was the main focus of the included studies. DCE studies showed patients gave a higher rank on health benefit and treatment process, while physicians gave a higher rank on adverse effects. Non-DCE studies suggested that patients were willing to take a higher risk of adverse effects or lower health benefit than physicians when accepting a treatment. CONCLUSIONS: Physicians and patients had important preference differences for cancer treatment. More sufficient communication is needed in cancer treatment decision-making.

China Health Related Outcomes Measures (CHROME): development of a descriptive system to support cardiovascular disease specific preference-based measure for the Chinese population.

PURPOSE: Preference-based measures have been increasingly recommended to measure health outcomes for economic evaluation. However, none of existing cardiovascular disease (CVD)-specific health-related quality of life (HRQoL) instruments are preference-based. This study aimed to develop the descriptive system of preference-based HRQoL instrument for Chinese patients with CVDs under the Initiative of China Health Related Outcomes Measures (CHROME). METHODS: Qualitative face-to-face interviews were conducted with Chinese patients with CVDs. Content analysis was employed to generate candidate items for the instrument. Then expert consultation and cognitive debriefing interviews were conducted to guide further selection and revision of the items. RESULTS: We interviewed 127 CVD patients with 67.7% being male and 63.8% living in the urban area. A hierarchical code book comprised of four themes, 20 categories, 62 sub-categories, and 207 codes, was developed. Candidate items were selected based on the criteria set by the Consensus-based Standards for the selection of health Measurement Instruments (COSMIN) methodology and ISPOR PRO guidance. An online survey and meeting with an expert advisory panel (n = 15) followed by cognitive debriefing interviews with 20 patients and 13 physicians were conducted to further select and revise the candidate items. The descriptive system of CHROME-CVD consists of 14 items, namely frequency and severity of chest pain, chest tightness, palpitation, shortness of breath, dizziness, fatigue, appetite, sleeping, mobility, daily activities, depression, worry, and social relationship. Four or five level responses were selected based on cognitive debriefing results to each item. CONCLUSION: The current study developed the descriptive system (items and response options) of CHROME-CVD, the future CVD-specific preference-based HRQoL instrument for Chinese CVD patients.

The long-term clinical benefits and economic costs associated with increased use of prophylaxis among patients with haemophilia A in China: Population-based predictions from 2018 to 2033.

AIM: To predict the long-term benefits and economic costs of the improvements in haemophilia care in China demonstrated by increasing use of prophylaxis, compared with the current status. METHODS: City-level predictions from 2018 to 2033 were conducted for five representative cities in China. The long-term clinical and economic outcomes in the scenario where haemophilia care has significantly improved and the existing scenario of haemophilia care were calculated and compared. The model input data were obtained from local records, expert interviews, published literature, and other sources. Outcome measures including number of bleeds and joint bleeds, number of target joints, disability rate, direct and indirect costs were calculated at the patient and population levels. RESULTS: The long-term predictions for 2033 demonstrated significantly improved bleed control and joint outcomes due to increased use of prophylaxis. The total number of averted bleed events per patient ranged from 3.9 in Shenyang to 16.1 in Zhengzhou in 2033, and the population-level averted bleed events ranged from 1963 in Xiamen to 14,868 in Zhengzhou. The treatment improvement also leads to significant economic costs driven by increase in clotting factor costs (more than 90%). At the population level, the additional total costs were highest in Zhengzhou (CNY 177.4 million) and lowest in Shenyang (CNY 45.4 million), due to their different population sizes and various existing treatment regimens. The outpatient and hospitalization costs decreased, while the factor costs increased. CONCLUSION: The long-term prophylaxis is associated with avoided bleed events and disabilities. The improved treatment regimens are also associated with a significant economic burden, driven by factor costs.

How Do Treatment Preferences of Patients With Cancer Compare With Those of Oncologists and Family Members? Evidence From a Discrete Choice Experiment in China.

OBJECTIVES: This study aimed to compare the treatment preference among oncologists, patients with lung cancer, and their family members in China. METHODS: A face-to-face discrete choice experiment survey was conducted among oncologists, patients, and their family members. Participants completed 13 choice sets describing 6 key attributes, namely, overall survival time, risk of severe adverse effect, severity of pain, appetite, physical functioning status, and monthly cost. Mixed logit model and latent class analysis were used to estimate attribute level preference weights and the relative importance (RI) for attributes. The willingness to pay (WTP) and maximum acceptable risk (MAR) were also estimated. The RI, WTP, and MAR of oncologists, patients, and family members were compared. RESULTS: A total of 121 oncologists and 161 dyads of patients and family members completed the survey. Overall survival time, physical functioning status, and pain were the 3 most important attributes across all 3 groups. Oncologists and family members had higher RI on overall survival time than patients (48% and 51% vs 38%). Patients had higher RI on physical functioning status and pain (23% and 14%) than oncologists (13% and 12%) and family members (16% and 11%). For extending survival, patients had the least WTP, and family members had the highest MAR. The latent class analysis identified 2 classes in the patient group and 3 classes in oncologist and family member groups. CONCLUSIONS: There were differences in preferences for survival, risk, quality of life, and costs associated with cancer treatments among patients, oncologists, and family members. This finding highlights the need of involving patients in treatment decision making in China.

Do Discrete Choice Experiments Approaches Perform Better Than Time Trade-Off in Eliciting Health State Utilities? Evidence From SF-6Dv2 in China.

OBJECTIVES: To explore the acceptability, consistency, and accuracy of eliciting health state utility values using discrete choice experiment (DCE) and DCE with life duration dimension (DCETTO) as compared with conventional time trade-off (TTO) by using the SF-6Dv2. METHODS: During face-to-face interviews, a representative sample of the general population in Tianjin, China, completed 8 TTO tasks and 10 DCE/DCETTO tasks, with the order of TTO and DCE/DCETTO being randomized. The fixed-effect model and conditional logit models were used for TTO and DCEs data estimation, respectively. Acceptability was assessed by self-reported difficulties in understanding/answering. Consistency was observed by the monotonicity of model coefficients. Accuracy was evaluated by investigating differences between observed and predicted TTO values using intraclass correlation coefficient, mean absolute difference, and root mean square difference. RESULTS: A total of 503 respondents (53.7% male; range, 18-86 years) were included, with comparable characteristics between respondents who completed DCE (N = 252) and DCETTO (N = 251). No significant difference was observed in self-reported difficulties among 3 approaches. The monotonicity of coefficients could not be achieved for 2 DCE approaches, even when combining the inconsistent levels. The health state utility values generated by DCE were generally higher than those generated by TTO, whereas DCETTO was lower than TTO. The TTO had a better prediction accuracy than the DCEs. CONCLUSIONS: Two DCE approaches are feasible for eliciting health state utility values; however, they are not considered to be easier to understand/answer than TTO. There are systematic differences in the health state utility values generated by 3 approaches. The issue of non-monotonicity from 2 DCE approaches remains a concern.

Adherence to statins and its impact on clinical outcomes: a retrospective population-based study in China.

BACKGROUND: While the benefit of adherence to statins on clinical outcomes has been proved, this benefit may be heterogeneous among patients who initiated statins for primary or secondary prevention purpose. This study aimed to investigate the impact of statin adherence on clinical outcomes among patients who initiated statins for primary and secondary prevention in China. METHODS: Adult patients in Tianjin Urban Employee Basic Medical Insurance database who initiated ≥2 prescriptions of statins from 2012 through 2013 were included and grouped into primary and secondary prevention subgroups according to their cardiovascular diseases (CVD) history during the prior 12-month baseline period. Proportion of days covered (PDC) was used to measure statin adherence in the initial 12-month follow-up. Clinical outcomes were measured by the incidence of major adverse cardiovascular events (MACE) during the 13th-24th months follow-up, and were compared between the patients with PDC ≥ 0.5 and patients with PDC < 0.5 using Cox regression models in primary and secondary prevention subgroups. Sensitivity analyses were conducted in propensity score matched groups. RESULTS: 99,655 patients were finally included. The mean (SD) PDC was 0.19 (0.15) in primary prevention subgroup (N = 34,372), with 5.4% patients had PDC ≥ 0.5. The patients with PDC ≥ 0.5 had a 37% reduced risk of MACE compared with patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 1.1% vs. 1.4%; all-adjusted HR = 0.63; 95% CI, 0.41-0.98). While, no significant difference was observed in the secondary prevention subgroup (N = 65,283) between patients with PDC ≥ 0.5 and patients with PDC < 0.5 (Unadjusted incidence rate of MACE: 4.6% vs. 2.8%; all-adjusted HR = 1.08, 95% CI, 0.92-1.28). These findings were confirmed by the sensitivity analyses in propensity score matched groups. CONCLUSIONS: Statin adherence was very poor in China, and statin adherence is associated with decreased risk of MACE in patients for primary prevention, while further exploration is needed for secondary prevention.

The Simplified Chinese version of SF-6Dv2: translation, cross-cultural adaptation and preliminary psychometric testing.

PURPOSE: To translate, cross-culturally adapt and preliminarily test the Simplified Chinese version of SF-6Dv2 among the Chinese general population. METHODS: The translation followed the international guidelines. Face-to-face cognitive debriefing was carried out in a small sample of the Chinese general population, using both think-aloud and retrospective probing methods. Preliminary psychometric properties (including acceptability, ceiling/floor effect and known-group validity) were investigated using a cross-sectional survey which was conducted in a representative sample of the general population in Tianjin, China. RESULTS: Translation was conducted by forward- and back-translation, followed by harmonization and expert review. Two minor modifications were made during cognitive debriefing. Five hundred and nine respondents (54.4% males, aged 18-86 years) participated in the psychometric testing survey. The mean (standard deviation) duration of finishing SF-6Dv2 was 96.9 s (58.5 s). No respondents claimed difficulties on understanding/answering, and no ceiling/floor effect was found in the total summary score. Known-group validity verified that the questionnaire was able to distinguish between subgroups in terms of whether having chronic conditions. CONCLUSIONS: The Simplified Chinese version of SF-6Dv2 is demonstrated to be conceptually equivalent with the original English version, which is also understandable and easy to finish among the Chinese general population.

Health care resource utilization and direct medical costs for patients with schizophrenia initiating treatment with atypical versus typical antipsychotics in Tianjin, China.

BACKGROUND: It is uncertain whether the extra acquisition costs of atypical antipsychotics over typical antipsychotics are offset by their other reduced resource use especially in hospital services in China. This study compared the psychiatric-related health care resource utilization and direct medical costs for patients with schizophrenia initiating atypical or typical antipsychotics in Tianjin, China. METHODS: Data were obtained from the Tianjin Urban Employee Basic Medical Insurance database (2008-2010). Adult patients with schizophrenia with ≥1 prescription for antipsychotics after ≥90-day washout and 12-month continuous enrollment after first prescription was included. Psychiatric-related resource utilization and direct medical costs of the atypical and typical cohorts were estimated during the 12-month follow-up period. Logistic regressions, ordinary least square (OLS), and generalized linear models (GLM) were employed to estimate differences of resource utilization and costs between the two cohorts. One-to-one propensity score matching was conducted as a sensitivity analysis. RESULTS: 1131 patients initiating either atypical (N = 648) or typical antipsychotics (N = 483) were identified. Compared with the typical cohort, the atypical cohort had a lower likelihood of hospitalization (45.8% vs. 56.7%, P < 0.001; adjusted OR: 0.58, P < 0.001) over the follow-up period. Medication costs for the atypical cohort were higher than the typical cohort ($438 vs. $187, P < 0.001); however, their non-medication medical costs were significantly lower ($1223 vs. $1704, P < 0.001). The total direct medical costs were similar between the atypical and typical cohorts before ($1661 vs. $1892, P = 0.100) and after matching ($1711 vs. 1868, P = 0.341), consistent with the results from OLS and GLM models for matched cohorts. CONCLUSIONS: The atypical cohort had similar total direct medical costs compared to the typical cohort. Higher medication costs associated with atypical antipsychotics were offset by a reduction in non-medication medical costs, driven by fewer hospitalizations.

Efficacy, Safety, and Treatment Burden of Aflibercept 2 mg and Ranibizumab in Retinal Vein Occlusion: A Systematic Review and Meta-analysis.

INTRODUCTION: This systematic review and meta-analysis aimed to provide an updated evidence base for clinical decision-making by comparing the efficacy and safety of aflibercept 2 mg and ranibizumab in treating retinal vein occlusion (RVO). METHODS: A systematic search was conducted using eight databases up to December 2021. Randomized controlled trials (RCTs) and real-world studies (RWSs) comparing aflibercept and ranibizumab in patients with RVO were evaluated. The primary outcomes assessed were efficacy, number of injections administered, and adverse events. RESULTS: Three RCTs (424 patients) and 11 RWSs (1415 patients) were included. For central RVO (CRVO), RCTs demonstrated a comparable efficacy, whereas RWSs showed that mean changes from baseline in best-corrected visual acuity (BCVA) and central retinal thickness (CRT) were significantly greater with aflibercept compared to ranibizumab; the number of injections of aflibercept was fewer than that of ranibizumab in RCTs, but similar in RWSs. For branch RVO (BRVO), no statistically significant difference in efficacy between the two drugs in RCTs/RWSs was observed, with fewer injections of aflibercept at 12 months in RWSs. The safety profiles of both drugs were similar for both CRVO and BRVO. CONCLUSIONS: For CRVO, aflibercept had similar efficacy and safety profile but with fewer injections versus ranibizumab in RCTs; RWSs showed greater BCVA improvement and CRT reduction with aflibercept than ranibizumab. For BRVO, RCTs showed similar in efficacy, safety, and injection numbers for both drugs, while RWSs demonstrated that aflibercept required fewer injections at 12 months of follow-up. Overall, this study provides updated evidence for clinical decision-making in the treatment of RVO.

The MVPs (masterful versatile players): Chromatin factors as pivotal mediators between 3D genome organization and the response to environment.

In recent years, the study of genome dynamics has become a prominent research field due to its influence on understanding the control of gene expression. The study of 3D genome organization has unveiled multiple mechanisms in orchestrating chromosome folding. Growing evidence reveals that these mechanisms are not only important for genome organization, but play a pivotal role in enabling plants to adapt to environmental stimuli. In this review, we provide an overview of the current knowledge concerning epigenetic factors and regulatory elements driving 3D genome dynamics and their responses to external stimuli. We discuss the most recent findings, previous evidence, and explore their implications for future research.

Apoptotic bodies inhibit inflammation by PDL1-PD1-mediated macrophage metabolic reprogramming.

Apoptosis triggers immunoregulation to prevent and suppress inflammation and autoimmunity. However, the mechanism by which apoptotic cells modulate immune responses remains largely elusive. In the context of allogeneic mesenchymal stem cells (MSCs) transplantation, long-term immunoregulation is observed in the host despite the short survive of the injected MSCs. In this study, utilizing a mouse model of acute lung injury (ALI), we demonstrate that apoptotic bodies (ABs) released by transplanted human umbilical cord MSCs (UC-MSCs) convert the macrophages from a pro-inflammatory to an anti-inflammatory state, thereby ameliorating the disease. Mechanistically, we identify the expression of programmed cell death 1 ligand 1 (PDL1) on the membrane of UC-MSCs-derived ABs, which interacts with programmed cell death protein 1 (PD1) on host macrophages. This interaction leads to the reprogramming of macrophage metabolism, shifting from glycolysis to mitochondrial oxidative phosphorylation via the Erk-dependent pathway in ALI. Importantly, we have reproduced the PDL1-PD1 effects of ABs on metabolic switch using alveolar macrophages from patients with ALI, suggesting the potential clinical implications of developing therapeutic strategies for the patients.

Apoptotic Vesicles Modulate Endothelial Metabolism and Ameliorate Ischemic Retinopathy via PD1/PDL1 Axis.

Pathological angiogenesis with subsequent disturbed microvascular remodeling is a major cause of irreversible blindness in a number of ischemic retinal diseases. The current anti-vascular endothelial growth factor therapy can effectively inhibit angiogenesis, but it also brings significant side effects. The emergence of stem cell derived extracellular vesicles provides a new underlining strategy for ischemic retinopathy. Apoptotic vesicles (apoVs) are extracted from stem cells from human exfoliated deciduous teeth (SHED). SHED-apoVs are delivered into the eyeballs of oxygen-induced retinopathy (a most common model of angiogenic retinal dieseases) mice through intravitreal injection. The retinal neovascularization and nonperfusion area, vascular structure, and density changes are observed during the neovascularization phase (P17) and vascular remodeling phase (P21), and visual function is measured. The expression of extracellular acidification rate and lactic acid testing are used to detect endothelial cells (ECs) glycolytic activity. Furthermore, lentivirus and neutralizing antibody are used to block PD1-PDL1 axis, investigating the effects of SHED-apoVs on glycolysis and angiogenic activities. This work shows that SHED-apoVs are taken up by ECs and modulate the ECs glycolysis, leading to the decrease of abnormal neovessels and vascular remodeling. Furthermore, it is found that, at the molecular level, apoVs-carried PD1 interacts with PDL1 on hypoxic ECs to regulate the angiogenic activation. SHED-apoVs inhibit pathological angiogenesis and promote vascular remodeling in ischemic retinopathy partially by modulating ECs glycolysis through PD1/PDL1 axis. This study provides a new potential strategy for the clinical treatment of pathological retinal neovascularization.

The application of drug behavior management methods in the treatment of dental fear and oral diseases in children: A review.

Oral behavior management methods include basic behavior management methods and drug behavior management methods. In many cases, dental treatment that cannot be done simply through basic behavior management is not possible. The uncooperative behavior of children with dental fear in oral treatment has increased the demand for medication based behavior management methods. Drug sedation can provide more effective analgesic and anti-anxiety effects, thereby helping to provide comfortable, efficient, and high-quality dental services. This article will review the drug sedation methods selected in clinical treatment of pediatric dental fear in recent years, as well as the safety and effectiveness of commonly used drugs, in order to provide guidance for dental professionals in clinical practice.

Protective Effects of Danmu Extract Syrup on Acute Lung Injury Induced by Lipopolysaccharide in Mice through Endothelial Barrier Repair.

OBJECTIVE: To investigate the effects of Danmu Extract Syrup (DMS) on lipopolysaccharide (LPS)-induced acute lung injury (ALI) in mice and explore the mechanism. METHODS: Seventy-two male Balb/C mice were randomly divided into 6 groups according to a random number table (n=12), including control (normal saline), LPS (5 mg/kg), LPS+DMS 2.5 mL/kg, LPS+DMS 5 mL/kg, LPS+DMS 10 mL/kg, and LPS+Dexamethasone (DXM, 5 mg/kg) groups. After pretreatment with DMS and DXM, the ALI mice model was induced by LPS, and the bronchoalveolar lavage fluid (BALF) were collected to determine protein concentration, cell counts and inflammatory cytokines. The lung tissues of mice were stained with hematoxylin-eosin, and the wet/dry weight ratio (W/D) of lung tissue was calculated. The levels of tumor necrosis factor-α (TNF-α), interleukin (IL)-6 and IL-1 ß in BALF of mice were detected by enzyme linked immunosorbent assay. The expression levels of Claudin-5, vascular endothelial (VE)-cadherin, vascular endothelial growth factor (VEGF), phospho-protein kinase B (p-Akt) and Akt were detected by Western blot analysis. RESULTS: DMS pre-treatment significantly ameliorated lung histopathological changes. Compared with the LPS group, the W/D ratio and protein contents in BALF were obviously reduced after DMS pretreatment (P<0.05 or P<0.01). The number of cells in BALF and myeloperoxidase (MPO) activity decreased significantly after DMS pretreatment (P<0.05 or P<0.01). DMS pre-treatment decreased the levels of TNF-α, IL-6 and IL-1 ß (P<0.01). Meanwhile, DMS activated the phosphoinositide 3-kinase/protein kinase B (PI3K/Akt) pathway and reversed the expressions of Claudin-5, VE-cadherin and VEGF (P<0.01). CONCLUSIONS: DMS attenuated LPS-induced ALI in mice through repairing endothelial barrier. It might be a potential therapeutic drug for LPS-induced lung injury.

Strictosamide promotes wound healing through activation of the PI3K/AKT pathway.

Nauclea officinalis, as a Chinese medicine in Hainan province, had the effect of treating lower limb ulcers, burn infections. In this paper, we studied the effect of Strictosamide (STR), the main bioactive compound in Nauclea officinals, on wound healing and explored its internal mechanism. Firstly, the wound healing potential of STR was evaluated in a rat model, demonstrating its ability to expedite wound healing, mitigate inflammatory infiltration, and enhance collagen deposition. Additionally, immunofluorescence analysis revealed that STR up-regulated the expression of CD31 and PCNA. Subsequently, target prediction, protein-protein interaction (PPI), gene ontology (GO), and pathway enrichment analyses were used to obtain potential targets, specific biological processes, and molecular mechanisms of STR for the potential treatment of wound healing. Furthermore, molecular docking was conducted to predict the binding affinity between STR and its associated targets. Additionally, in vivo and in vitro experiments confirmed that STR could increase the expression of P-PI3K, P-AKT and P-mTOR by activating the PI3K/AKT signaling pathway. In summary, this study provided a new explanation for the mechanism by which STR promotes wound healing through network pharmacology, suggesting that STR may be a new candidate for treating wound.

Strictosamide alleviates acute lung injury via regulating T helper 17 cells, regulatory T cells, and gut microbiota.

BACKGROUND: Nauclea officinalis (Pierre ex Pit.) Merr. & Chun (Rubiaceae) is widely used to treat respiratory diseases in China. Strictosamide is its main active component and has significant anti-inflammatory activity. However, the effects and molecular mechanisms of strictosamide in the treatment of acute lung injury (ALI) remain largely unknown. PURPOSE: This study aimed to examine the regulatory effects of strictosamide on T helper 17 cells (Th17 cells)/Regulatory T cells (Treg cells) and gut microbiota in ALI-affected mice. MATERIALS AND METHODS: The ALI model was induced using lipopolysaccharide (LPS) intraperitoneal injection. Hematoxylin-eosin (H&E) staining, the number of inflammatory cells in broncho-alveolar lavage fluid (BALF), the Wet/Dry (W/D) ratio, and myeloperoxidase (MPO) activity were utilized as evaluation indices for the therapeutic efficacy of strictosamide on ALI. Flow cytometry (FCM), enzyme-linked immune sorbent assay (ELISA), quantitative reverse transcription polymerase chain reaction (qRT-PCR), and western blotting were used to determine the regulation of strictosamide on the Th17/Treg cells and the STAT3/STAT5 signaling pathway. The analysis of gut microbiota was conducted using 16S rDNA sequencing. The verification of the relationship between the gut microbiome and immune function was conducted using Spearman analysis. RESULTS: Strictosamide attenuated inflammation on ALI induced by LPS, which reduced the levels of Th17-related factors interleukin (IL)-6 and IL-17 and increased Treg-related factors IL-10 and transforming growth factor (TGF)-ß. In the spleens and whole blood, strictosamide reduced the proportion of Th17 cells and increased the proportion of Treg cells. Furthermore, strictosamide increased Forkhead/winged helix transcription factor 3 (Foxp3) and p-STAT5 protein expression while inhibiting Retinoid-related orphan nuclear receptors-γt (RORγt) and p-STAT3 expression. Moreover, strictosamide reshaped the diversity and structure of the gut microbiota, and influence the associations between immune parameters and gut microbiota in ALI mice. CONCLUSIONS: In summary, the results of the current investigation showed that strictosamide has a therapeutic impact on LPS-induced ALI. The mechanism of action of this effect may be associated with the modulation of Th17 and Treg cells differentiation via the SATA signaling pathway, as well as the impact of the gut microbiota.