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IntroductionUlcerative colitis (UC) is a chronic inflammatory disease. Patients with UC typically exhibit disruption of the Treg/Th17 immune axis, but its exact mechanism is still unclear.MethodsThis study first analyzed RNA- seq data from public databases of humans and mice, and in vitro cytology experiments were conducted to induce or inhibit the expression of SIRT1. In vivo, UC mice were treated with moxibustion and SIRT1 inhibitor EX-527 to confirm the changes in the transcription factors identified through analysis of the datasets.ResultsThe results show that Treg/Th17 axis disruption is an important feature of UC. Differential gene expression and immune infiltration analysis showed that upstream transcription factors, including Forkhead box P3 (FOXP3), were significantly disrupted. In vitro cytology experiments, the results indicate that SIRT1 is activated in LPS induced inflammation, subsequently perturbing the Treg/Th17 immune balance axis. Finally, in vivo studies, the results have shown that administering EX-527 to inhibit SIRT1 leads to an increasing in FOXP3 expression and a decreasing in RORγt expression in UC colon tissue. In addition, the results indicate that traditional Chinese moxibustion can down regulate the expression of SIRT1, directly affecting the balance of Th17/Treg axis, and the combined use of EX-527 further improves the therapeutic effect of moxibustion.ConclusionOur research shows that inhibition SIRT1 can regulate Treg and Th17 immune balance axis. This finding indicates a new important potential target for the treatment of UC.

Abstract Our center has observed a substantial increase in the detection rate of fetal left–right(LR) asymmetry disorders between March and May 2023. This finding has raised concerns because these pregnant women experienced the peak outbreak of SARS-CoV-2 in China during their first trimester. To explore the relationship between maternal SARS-CoV-2 infection and fetal LR asymmetry disorders. A retrospective collection of clinical and ultrasound data diagnosed as fetal LR asymmetry disorders was conducted from January 2018 to December 2023. The case–control study involved fetuses with LR asymmetry disorders and normal fetuses in a 1:1 ratio. We evaluated and compared the clinical and fetal ultrasound findings in pregnant women with SARS-CoV-2 infection and pregnant women without infection. The Student t-test was utilized to compare continuous variables, while the chi-squared test was employed for univariable analyses. The incidence rate of LR asymmetry disorders from 2018 to 2023 was as follows: 0.17‰, 0.63‰, 0.61‰, 0.57‰, 0.59‰, and 3.24‰, respectively. A total of 30 fetuses with LR asymmetry disorders and 30 normal fetuses were included. This case–control study found that SARS-CoV-2 infection (96.67% vs 3.33%, P = .026) and infection during the first trimester (96.55% vs 3.45%, P = .008) were identified as risk factors. The odds ratio values were 10.545 (95% CI 1.227, 90.662) and 13.067 (95% CI 1.467, 116.419) respectively. In cases of SARS-CoV-2 infection in the first trimester, the majority of infections (88.1%, 37/42) occurred between 5 and 6 weeks of gestation. We found that 43.7% (66/151) of fetuses with LR asymmetry disorder had associated malformations, 90.9% (60/66) exhibited cardiac malformations. SARS-CoV-2 infection during the first trimester significantly increases the risk of fetal LR asymmetry disorders, particularly when the infection occurs between 5 and 6 gestation weeks. The most common associated malformation is heart malformation.

Transcatheter aortic valve implantation (TAVI) was originally devised as a treatment for patients with aortic stenosis (AS). It has since emerged as a beneficial alternative to surgical aortic valve replacement (SAVR), extending its reach to a broader array of patients. Our objective was to illustrate the developmental trends and focus areas in TAVI research. We sourced a total of 11,480 research papers on TAVI, published between 1994 and 2022, from the Web of Science Core Collection (WoSCC) database. We conducted a bibliometric analysis of these publications, generating cooperation maps, performing co-citation analysis of journals and references, and carrying out a cluster analysis of keywords. Our findings indicate that TAVI research grapples with numerous clinical challenges. We created knowledge maps that highlight contributing countries/institutions, authors, journals with high publication and citation rates, and notable references in this domain. North America and Europe have been at the forefront of research within the TAVI field. The institutions and authors from these regions exert significant influence in this area of study. Beginning in 2009, China has progressively expanded its research on TAVI over the past two decades. We anticipate that future research will increasingly focus on three key areas: implementation scope, lifelong management, outcomes and predicting the risk of TAVI. Research on TAVI is flourishing. Cooperation among different countries and institutions in this field must be strengthened in the future, especially for developing counties.

The clinical utilization of doxorubicin (Dox) in various malignancies is restrained by its major adverse effect: irreversible cardiomyopathy. Extensive studies have been done to explore the prevention of Dox cardiomyopathy. Currently, ferroptosis has been shown to participate in the incidence and development of Dox cardiomyopathy. Sorting Nexin 3 (SNX3), the retromer-associated cargo binding protein with important physiological functions, was identified as a potent therapeutic target for cardiac hypertrophy in our previous study. However, few study has shown whether SNX3 plays a critical role in Dox-induced cardiomyopathy. In this study, a decreased level of SNX3 in Dox-induced cardiomyopathy was observed. Cardiac-specific Snx3 knockout (Snx3-cKO) significantly alleviated cardiomyopathy by downregulating Dox-induced ferroptosis significantly. SNX3 was further demonstrated to exacerbate Dox-induced cardiomyopathy via induction of ferroptosis in vivo and in vitro, and cardiac-specific Snx3 transgenic (Snx3-cTg) mice were more susceptible to Dox-induced ferroptosis and cardiomyopathy. Mechanistically, SNX3 facilitated the recycling of transferrin 1 receptor (TFRC) via direct interaction, disrupting iron homeostasis, increasing the accumulation of iron, triggering ferroptosis, and eventually exacerbating Dox-induced cardiomyopathy. Overall, these findings established a direct SNX3–TFRC–ferroptosis positive regulatory axis in Dox-induced cardiomyopathy and suggested that targeting SNX3 provided a new effective therapeutic strategy for Dox-induced cardiomyopathy through TFRC-dependent ferroptosis.

Abstract Irritable bowel syndrome (IBS) and ulcerative colitis (UC) are two intestinal diseases with different pathological changes. Electroacupuncture (EA) at Zusanli (ST36) on both IBS and UC is widely used in clinic practice. But it is unclear whether acupuncture at one acupoint can treat two different intestinal diseases at different layers of intestinal barrier. To address this question, we explored three intestinal barrier lesions in IBS and UC mice with the aid of transcriptome data analysis and studied the efficacy of EA at ST36 on them. The transcriptome data analysis showed that both UC and IBS had disrupted intestinal barrier in various layers. And both UC and IBS had epithelial barrier lesions with reduction of ZO-1, Occludin and Claudin-1, while UC rather than IBS had the destruction of the mucus barrier with less MUC2 expression. As to the vascular barrier, UC showed a higher CD31 level and mesenteric blood flow reduction, while IBS showed a lower PV-1 level. EA at ST36 can significantly improve the above lesions of intestinal barrier of IBS and UC. Our results gave more details about the comprehensive protective effect of EA for UC and IBS. We guess the effect of acupuncture may be a kind of homeostasis regulation.

ObjectivesThis study aimed to evaluate the feasibility of direct visualization of a normal fetal palate and detect cleft palate in the first trimester with a novel three-dimensional ultrasound (3D US) technique, Crystal and Realistic Vue (CRV) rendering technology.MethodsTwo-dimensional (2D) images and 3D volumes of healthy and cleft palate fetuses at 11–13+6 weeks were obtained prospectively. 2D ultrasound views included the coronal view of the retronasal triangle and the midsagittal view of the face. 3D-CRV views were analyzed by multiplanar mode display. The pregnancy outcomes of all fetuses were determined during the follow-up period.ResultsIn our study, 124 fetuses were recruited, including 100 healthy fetuses and 24 cleft palate fetuses. The cleft palate with lip was observed in 23 fetuses (bilateral in 15, unilateral in 6, median in 2), and one cleft palate was only found in the abnormal group. The bilateral (n = 12) and median (n = 2) cleft palates with lips and the cleft palate alone (n = 1) were associated with other anatomical or chromosomal abnormalities, and one unilateral cleft palate with cleft lip had concomitant NT thickening. In the cleft palate fetus group, 16 fetuses suffered intrauterine death, which was associated with other structural or chromosomal abnormalities in 14 fetuses, seven cases were terminated after consultation, and one was delivered at term. The coronal view of the retronasal triangle and the midsagittal view was easily obtained in all fetuses. 3D-CRV images of palatal parts were clearly obtained in all cases. Unilateral, bilateral, and median cleft palates with cleft lips were visually demonstrated and classified by the 3D-CRV technique.ConclusionIt is feasible to identify the palate by 3D-CRV in the first trimester in both healthy and cleft palate fetuses. Together with 2D ultrasonography as a complementary diagnostic tool, 3D-CRV is helpful in classifying the cleft palate with a reasonable degree of certainty.

Endometrial cancer (EC) is a prevalent epithelial malignancy in the uterine corpus’s endometrium and myometrium. Regulating apoptosis of endometrial cancer cells has been a promising approach for treating EC. Recent in-vitro and in-vivo studies show that numerous extracts and monomers from natural products have pro-apoptotic properties in EC. Therefore, we have reviewed the current studies regarding natural products in modulating the apoptosis of EC cells and summarized their potential mechanisms. The potential signaling pathways include the mitochondria-dependent apoptotic pathway, endoplasmic reticulum stress (ERS) mediated apoptotic pathway, the mitogen-activated protein kinase (MAPK) mediated apoptotic pathway, NF-κB-mediated apoptotic pathway, PI3K/AKT/mTOR mediated apoptotic pathway, the p21-mediated apoptotic pathway, and other reported pathways. This review focuses on the importance of natural products in treating EC and provides a foundation for developing natural products-based anti-EC agents.

This review outlined evidence that purinergic signaling is involved in the modulation of blood-brain barrier (BBB) permeability. The functional and structural integrity of the BBB is critical for maintaining the homeostasis of the brain microenvironment. BBB integrity is maintained primarily by endothelial cells and basement membrane but also be regulated by pericytes, neurons, astrocytes, microglia and oligodendrocytes. In this review, we summarized the purinergic receptors and nucleotidases expressed on BBB cells and focused on the regulation of BBB permeability by purinergic signaling. The permeability of BBB is regulated by a series of purinergic receptors classified as P2Y1, P2Y4, P2Y12, P2X4, P2X7, A1, A2A, A2B, and A3, which serve as targets for endogenous ATP, ADP, or adenosine. P2Y1 and P2Y4 antagonists could attenuate BBB damage. In contrast, P2Y12-mediated chemotaxis of microglial cell processes is necessary for rapid closure of the BBB after BBB breakdown. Antagonists of P2X4 and P2X7 inhibit the activation of these receptors, reduce the release of interleukin-1 beta (IL-1β), and promote the function of BBB closure. In addition, the CD39/CD73 nucleotidase axis participates in extracellular adenosine metabolism and promotes BBB permeability through A1 and A2A on BBB cells. Furthermore, A2B and A3 receptor agonists protect BBB integrity. Thus, the regulation of the BBB by purinergic signaling is complex and affects the opening and closing of the BBB through different pathways. Appropriate selective agonists/antagonists of purinergic receptors and corresponding enzyme inhibitors could modulate the permeability of the BBB, effectively delivering therapeutic drugs/cells to the central nervous system (CNS) or limiting the entry of inflammatory immune cells into the brain and re-establishing CNS homeostasis.

IntroductionChromoblastomycosis (CBM) is a form of chronic mycosis that affects the skin and mucous membranes and is caused by species of dematiaceous fungi including Exophiala spp., Phialophora spp., and Fonsecaea spp. The persistence of this disease and limitations associated with single-drug treatment have complicated efforts to adequately manage this condition.MethodsIn this study, a microdilution assay was used to explore the synergistic antifungal activity of everolimus (EVL) in combination with itraconazole (ITC), voriconazole (VRC), posaconazole (POS), and amphotericin B (AMB) against a range of clinical dematiaceous fungal isolates.ResultsThese analyses revealed that the EVL+POS and EVL+ITC exhibited superior in vitro synergistic efficacy, respectively inhibiting the growth of 64% (14/22) and 59% (13/22) of tested strains. In contrast, the growth of just 9% (2/22) of tested strains was inhibited by a combination of EVL+AMB, and no synergistic efficacy was observed for the combination of EVL+VRC.DiscussionOverall, these findings indicate that EVL holds promise as a novel drug that can be synergistically combined with extant antifungal drugs to improve their efficacy, thereby aiding in the treatment of CBM.

Background:Aloe vera is a medically valuable plant with anti-epileptic activity; however, its mechanism of action remains unknown. In this study, network pharmacological, in vitro, and in vivo experiments were carried out to explore the potential anti-epileptic components and targets of Aloe vera.Methods: The main active components of Aloe vera were identified by searching the Traditional Chinese Medicine System Pharmacology database. Targets of Aloe vera were predicted using SwissTargetPrediction, whereas information about the epilepsy disease targets was obtained from Gene Cards. The protein–protein interaction network and core targets were screened according to the topological structure and CytoNCA plugin. The glutamate-induced HT22 cell line and pentylenetetrazol-induced seizure rats were used to confirm the effect of aloesone by detecting reactive oxygen species (ROS) and apoptosis, and predicting the targets.Results: A total of 14 core active components were selected based on the screening criteria of oral bioavailability ≥30% and drug-likeness ≥ 0.10. Four compounds, namely linoleic acid, aloesone, isoeleutherol glucosiden qt, and anthranol, demonstrated the potential ability of crossing the blood-brain barrier. A total of 153 targets associated with epilepsy were predicted for the four compounds. Moreover, after network analysis with CytoNCA, 10 targets, namely, MAPK1, SRC, MARK3, EGFR, ESR1, PTGS2, PTPN11, JAK2, PPKCA, and FYN, were selected as the core genes, and SRC, which has been predicted to be the target of aloesone and anthranol, exhibited the highest subgraph centrality value. In vitro experiments confirmed that aloesone treatment significantly inhibited the glutamate-induced neuronal injury by reducing the intracellular ROS content and the early phase of apoptosis. Additionally, treatment with 50 mg/kg aloesone resulted in anti-seizure effects by reducing the seizure score and prolonging the latent period in acute and chronic rats. Furthermore, aloesone treatment increased the phosphorylation of c-SRC at Y418 and reduced the phosphorylation at Y529, simultaneously activating c-SRC.Conclusion: Integrating network pharmacology with in vitro and in vivo experiments demonstrated that aloesone, which inhibited seizure by activating c-SRC, is a potential anti-seizure compound present in Aloe vera.

Objective To investigate the effect of different effect compartment concentrations of propofol on the ste-reotactic electroencephalography (SEEG) of the left cerebral neocortex and limbic system in adult patients with epilepsy. Methods Fourteen patients undergoing elective electrode removal following robot-guided stereotactic implantation of left intracerebral electrodes in the Department of Epilepsy Surgery at our hospital from January 2021 to December 2022 were selected. Patients were divided into neocortex group and limbic system group according to the location of electrodes in the brain. The power range and percentage of δ, θ, α, β, and γ waves on SEEG at the intraoperative effect compartment concentrations of propofol of 0, 2, 3, 4, and 5 mg/L (concentrations of D1-D5) as well as the modulation index (MI) of phase-amplitude coupling (PAC) in the wave bands of δ-γ, θ-γ, α-γ, and β-γ were recorded and compared between the two groups. Results The power ranges of γ wave on SEEG of the left limbic system and cerebral neocortex were significantly lower at the concentrations of D2-D5 than at the concentration of D1 (F=15.13,20.33,t=4.33-8.72,P