Active targeting microemulsion-based thermosensitive hydrogel against periodontitis by reconstructing Th17/Treg homeostasis via regulating ROS-macrophages polarization cascade.

Periodontitis is a multifactorial inflammatory disease characterized by severe alveolar bone damage and attachment loss. The imbalance of T help 17 (Th17) / regulatory T cells (Treg) induces excessive interleukin (IL)-17, which leads to alveolar bone damage and aggravates the development of periodontitis. Therefore, we proposed a therapeutic strategy to restore Th17/Treg homeostasis by interfering reactive oxygen species (ROS)-macrophage polarization cascade using active targeting microemulsions-based thermosensitive hydrogel. Folic acid-modified quercetin-loaded microemulsions (FA-Qu-MEs) were dispersed in poloxamer 407 and poly(N-isopropylacrylamide) matrix of hydrogel (FA-Qu-MEs@Gel). FA-Qu-MEs@Gel could be locally injected into the periodontal pocket and sustainedly release drugs. FA-Qu-MEs exhibited excellent ROS scavenging potency by targeting macrophages, resulting M1 phenotype macrophage from to M2 phenotype macrophage. Subsequently, the phenotypic changes of macrophages lead to decreased expression of IL-6 and tumor necrosis factor-α, which inhibited activated Th17, while IL-10 secreted by M2 macrophages promoted Treg differentiation. Finally, the restored Th17/Treg homeostasis reduced the level of IL-17 to accelerate alveolar bone regeneration. This study deigns a novel system that promote alveolar bone regeneration by remodeling Th17/Treg homeostasis via regulating ROS-macrophages polarization cascade for periodontitis treatment.

Identification and characterization of a novel antifungal compound tubeimoside I targeting cell wall.

Due to fungal diseases that threaten immunocompromised patients, along with the limited availability of antifungal agents, there is an urgent need for new antifungal compounds to treat fungal infections. Here, we aimed to identify potential antifungal drugs from natural products using the fission yeast Schizosaccharomyces pombe as a model organism since it shares many features with some pathogenic fungi. Here, we identified tubeimoside I (TBMS1), an extract from Chinese herbal medicine, that showed strong antifungal activity against S. pombe. To gain insight into the underlying mechanism, we performed transcriptomics analyses of S. pombe cells exposed to TBMS1. A significant proportion of the differential expressed genes were involved in cell wall organization or biogenesis. Additionally, TBMS1 treatment of S. pombe cells resulted in pleiotropic phenotypes, including increased sensitivity to ß-glucanase, enhanced calcineurin activity, translocation of GFP-Prz1 to the nucleus, as well as enhanced dephosphorylation of Prz1, suggesting that TBMS1 disrupted cell wall integrity of S. pombe cells. Notably, calcofluor staining showed that abnormal deposits of cell wall materials were observed in the septum and cell wall of the TBMS1-treated cells, which were further corroborated by electron microscopy analysis. We also found that oxidative stress might be involved in the antifungal action of TBMS1. Moreover, we confirmed the antifungal activities of TBMS1 against several clinical isolates of pathogenic fungi. Collectively, our findings suggest that TBMS1, a novel antifungal compound, exerts its antifungal activity by targeting cell walls, which may pave the way for the development of a new class of antifungals. IMPORTANCE: Fungal infections pose a serious threat to public health and have become an emerging crisis worldwide. The development of new antifungal agents is urgently needed. Here, we identified compound tubeimoside I (TBMS1) for the first time showing strong antifungal activity, and explored the underlying mechanisms of its antifungal action by using the model yeast Schizosaccharomyces pombe. Notably, we presented multiple evidence that TBMS1 exerts its antifungal activity through targeting fungal cell walls. Moreover, we verified the antifungal activities of TBMS1 against several pathogenic fungi. Our work indicated that TBMS1 may serve as a novel antifungal candidate, which provides an important foundation for designing and developing new cell wall-targeting agents for combating life-threatening fungal infections.

The Influence of Maternal Folate Status on Gestational Diabetes Mellitus: A Systematic Review and Meta-Analysis.

Maternal folate has been shown to relate to the risk of gestational diabetes mellitus (GDM). However, the existing studies have yielded inconsistent conclusions. The purpose of this study was to systematically review the association between maternal folate status and the risk of GDM. Observational studies up to 31 October 2022 were included. Study characteristics, the means and standard deviations (SDs) of folate levels (serum/red blood cell (RBC)), the odds ratios (ORs) with 95% confidence intervals (CIs) and the time for folate measurement were extracted. Compared with the non-GDM group, serum and RBC folate levels in women with GDM were significantly higher. Our subgroup analysis demonstrated that serum folate levels in the GDM group were significantly higher than in the non-GDM group only in the second trimester. RBC folate levels in the GDM group were significantly higher than in the non-GDM group in the first and second trimesters. Taking serum/RBC folate levels as continuous variables, the adjusted odds ratios of GDM risk showed that increased serum folate concentration rather than RBC folate elevated the risk of GDM. In the descriptive analysis, five studies reported high serum folate levels increased GDM risk, whereas the other five showed no association between serum folate levels and GDM risk. Moreover, the rest three studies pointed out high RBC folate levels increased GDM risk. Altogether we found that the risk of GDM is associated with high serum/plasma and RBC folate levels. Future studies should determine the recommended folic acid cutoff balancing the risk for GDM and fetal malformations.

Heme induced progesterone-resistant profiling and promotion of endometriosis in vitro and in vivo.

Endometriosis is an estrogen-dependent, progesterone-resistant gynecological disease with an unknown pathogenesis. Compared to women without endometriosis, women with endometriosis have a remarkably high heme level in the peritoneal fluid. To further investigate the pathomechanisms of heme in endometriosis, we aimed to identify the dysregulated expression of heme-trafficking proteins, such as PGRMC1/2 that are also receptors that mediate the non-genomic responses to progesterone, and heme-degrading enzymes between ectopic endometrial stromal cells and their normal counterparts. We found that heme could regulate progesterone receptor-related gene expression. Functional human endometrial stromal cell experiments showed that heme promotes cell proliferation and migration in a heme oxygenase-1-independent manner; moreover, blocking oxidative phosphorylation/ATP generation could abolish these effects of heme in vitro, whereas intraperitoneal hemopexin administration could alleviate heme-triggered ectopic lesions in vivo. Therefore, heme likely mediates the induction of progesterone resistance and simultaneously induces endometriosis via the mitochondrial oxidative phosphorylation pathway.

Peritoneal immune microenvironment of endometriosis: Role and therapeutic perspectives.

Endometriosis, an estrogen-dependent chronic inflammatory disease characterized by the growth of endometrium-like tissues outside the uterine cavity, affects 10% of reproductive-age women. Although the pathogenesis of endometriosis is uncertain, it is widely accepted that retrograde menstruation results in ectopic endometrial tissue implantation. Given that not all women with retrograde menstruation develop endometriosis, immune factors have been hypothesized to affect the pathogenesis of endometriosis. In this review, we demonstrate that the peritoneal immune microenvironment, including innate immunity and adaptive immunity, plays a central role in the pathogenesis of endometriosis. Current evidence supports the fact that immune cells, such as macrophages, natural killer (NK) cells, dendritic cells (DCs), neutrophils, T cells, and B cells, as well as cytokines and inflammatory mediators, contribute to the vascularization and fibrogenesis of endometriotic lesions, accelerating the implantation and development of ectopic endometrial lesions. Endocrine system dysfunction influences the immune microenvironment through overexpressed estrogen and progesterone resistance. In light of the limitations of hormonal therapy, we describe the prospects for potential diagnostic biomarkers and nonhormonal therapy based on the regulation of the immune microenvironment. Further studies are warranted to explore the available diagnostic biomarkers and immunological therapeutic strategies for endometriosis.

Role and progress of artificial intelligence in radiodiagnosing vascular calcification: a narrative review.

Background and Objective: Vascular calcification has important clinical significance due to its vital prognostic value for cardiovascular diseases, chronic kidney disease (CKD), diabetes, fracture, and other multisystem diseases. Radiology is the main diagnostic method of it, but facing great pressure such as the increasing workload and decreasing working accuracy rate. Therefore, radiology needs to find a way out to better realize the clinical value of vascular calcification. Artificial intelligence (AI) encompasses any algorithm imitating human intelligence. AI has shown great potential in image analysis, such as its high speed and accuracy, becoming the savior of the current situation. In order to promote more rational utilization, the role and progress of AI in this field were reviewed. Methods: A search was conducted in PubMed and Web of Science. The key words included "artificial intelligence", "machine learning", "deep learning", and "vascular calcification". The qualitative analysis of literature was achieved through repeated deliberation after refining valuable content. The theme is the role and progress of AI in the diagnostic radiology of vascular calcification. Key Content and Findings: Sixty-two articles were included. AI has been applied to the diagnostic radiology of 5 types of vascular calcification, including coronary artery calcification (CAC), thoracic aortic calcification (TAC), abdominal aortic calcification (AAC), carotid artery calcification, and breast artery calcification (BAC). Deep learning (DL), the latest technology in this field has been well applied and satisfactorily performed. Radiologists have been able to achieve efficient diagnosis of 5 types of vascular calcification through AI, with reliable accuracy. Conclusions: Increasingly, advanced AI has achieved an accuracy comparable to that of human experts, with a faster speed. Moreover, the ability to reduce noise and artifacts enables more imaging equipment to obtain reliable quantification. AI has acquired the ability to cooperate with radiology departments in future work. However, the research in AAC and carotid artery calcification can be more in-depth, and more types of vascular calcification and more fields of radiology should be expanded to. The interpretation of results made by AI and the promotion of existing achievements to the development of other disciplines are also the focus in future.

Advances in positron emission tomography tracers related to vascular calcification.

Microcalcification, a type of vascular calcification, increases the instability of plaque and easily leads to acute clinical events. Positron emission tomography (PET) is a new examination technology with significant advantages in identifying vascular calcification, especially microcalcification. The use of the 18F-NaF is undoubtedly the benchmark, and other PET tracers related to vascular calcification are also currently in development. Despite all this, a large number of studies are still needed to further clarify the specific mechanisms and characteristics. This review aimed at providing a summary of the application and progress of different PET tracers and also the future development direction.

Further Insights into the Performance of Silylated Polyacrylamide-Based Relative Permeability Modifiers in Carbonate Reservoirs and Influencing Factors.

We have previously used surface chemistry analysis techniques to optimize the functionalization of carbonate rocks with a silylated polyacrylamide-based relative permeability modifier (RPM). The RPM is expected to selectively reduce the permeability to water in a hydrocarbon reservoir setting, resulting in a reduction in the amount of produced water while maintaining the production of oil/gas. This study will focus on using core flooding techniques with brine/crude oil under reservoir conditions (i.e., 1500 psi pore pressure and 60 °C temperature) to understand the impact of a silylated polyacrylamide-based RPM on the fluid transport properties in carbonate rocks. The effects of RPM concentration, brine salinity, rock permeability, and pore structure on permeability characteristics were studied. Scanning electron microscopy (SEM) combined with energy dispersive spectroscopy (EDX) provided visual images of the polymer adsorbed onto the rock surfaces and confirmed the attachment of the polymer on the surface of the rock pore space after treatment. The relative percentage of Si increased from 1.65 to 13.55%, and the relative percentage of N increased to 4.54%. Core flooding showed that increasing the PAM-co-AA (poly acrylamide-co-acrylic acid partial sodium salt) concentration resulted in residual resistance factors for oil (RRFoil) and brine (RRFbrine) that were greater than 1. However, there was a modest decrease in the disproportionate permeability reduction (DRP) ratio (RRFbrine/RRFoil) from 1.75 to 1.60 when the polymer concentration was increased from 0.05 to 0.1 wt %. Furthermore, the RRFbrine values decreased slightly from 120 to 62 with increasing salinity (i.e., 1-10% NaCl) because of electrostatic shielding caused by charged ions in brine and the RPM. The cross-over points of relative permeability in these four samples shifted to the right because of the larger decrease in relative water permeability compared with relative oil permeability. End-point relative permeability to water in sample C-5 decreased by 80%, showing a reduction greater than that in the sample C-2 (i.e., 74%). Kr curves indicated a stronger formation damage in sample C-1, C-2, and C-4 than in sample C-5. Rock samples with a higher initial permeability exhibited a higher RRFbrine to RRFoil ratio (i.e., 3.05) under similar test conditions. This can be attributed to a larger pore radius, which was verified by nuclear magnetic resonance (NMR) measurements. Furthermore, a detailed mechanism has been proposed to understand the effects of the RPM on fluid transport in porous carbonate cores. In this study, SEM-EDX and NMR measurements combined with core flooding tests provide insights into the performance of silylated polyacrylamide-based RPMs and benefit its future implementation in carbonate reservoirs.