Comparative Activities of Three Compounds from Citrus aurantium L. var. amara Engl. to Improve Oxidized Low-Density Lipoprotein-Induced Lipid Deposition.

The active ingredients of Citrus aurantium have been shown to possess a variety of biological activities, especially anti-inflammatory effects. However, its antiatherosclerotic effects need to be further investigated. The aim of this study is to identify compounds with antiatherosclerotic effects from C. aurantium and to further investigate their mechanisms. Three compounds were separated, and then their antiatherosclerotic effect on foam cells induced by oxidized low-density lipoprotein (ox-LDL) was screened by oil red O staining, BODIPY staining, and Dil-ox-LDL uptake measurement. Cholesterol uptake, cholesterol efflux, RT-PCR, and Western blot analysis were used to comprehensively and comparatively explore the potential mechanisms. Nobiletin (NOB), caffeine (CAF), and naringin (NARG), which were separated from C. aurantium, mainly inhibit the formation of foam cells in different ways. NOB reduced cholesterol uptake and enhanced cholesterol efflux and mainly regulated the expressions of ABCA1, ABCG1, and SRA1. CAF promoted cholesterol efflux, mainly by stimulating the expressions of ABCA1 and ABCG1. NARG was more effective in reducing the expression of SRA1 and CD36, which indicated that NARG mainly prevented atherosclerosis by blocking cholesterol uptake. The above results show in detail the antiatherosclerotic activity and mechanism of these compounds, making contributions to their potential applications.

(-)-α-Bisabolol inhibits D-Gal-induced HSF cellular senescence in vitro and prevents skin aging in vivo by reducing SASP.

Objectives: To study the anti-aging effect of (-)-α-bisabolol ((-)-α-bis) on the skin and preliminarily clarify its mechanism. Materials and Methods: Human skin fibroblasts (HSF) were induced senescence by D-Galactose. Senescence ß-galactosidase staining was utilized to evaluate the senescence of HSF. TNF-α, IL-6, IL-8, IL-1ß, CCL-2, CCL-5, and MMP-9 in senescence-as-sociated secretory phenotype (SASP) were detected by RT-qPCR. Meanwhile, aged BALB/c mice were applied topically with 0.5% and 2%(-)-α-bis gel for 30 days continuously to evaluate anti-aging parameters on the skin such as surface measurement, the Trans Epidermal Water Loss (TEWL), and skin barrier index of dorsal skin. Then, HE staining, Masson staining, and IHC were applied to measure epidermal thickness, collagen fiber content in the dermis, and content of dermal collagen I, respectively. Last, SOD, MDA, and HYP contents of the back skin tissue of mice were also detected. Results: (-)-α-Bis reduced the expression of senescence-associated ß-galactosidase (SA-ß-gal) and expression levels of SASP in HSF cells stimulated by D-Gal (P<0.05). Mice aged 9 months were applied locally with (-)-α-bis gel to improve skin aging, the TEWL and skin barrier index of dorsal skin, and ameliorate the epidermal thickness and contents of dermal collagen fibers and collagen I (P<0.05). Furthermore, (-)-α-bis up-regulated the mRNA expression levels of elastin and collagen III effectively (P<0.05). Conclusion: (-)-α-Bis can delay the senescence of HSF cells by reducing the expression of SA-ß-gal and SASP factors in vitro. Improved skin barrier function as well as SASP is responsible for the delay of skin aging in vivo.

Construction and verification of atopic dermatitis diagnostic model based on pyroptosis related biological markers using machine learning methods.

OBJECTIVE: The aim of this study was to construct a model used for the accurate diagnosis of Atopic dermatitis (AD) using pyroptosis related biological markers (PRBMs) through the methods of machine learning. METHOD: The pyroptosis related genes (PRGs) were acquired from molecular signatures database (MSigDB). The chip data of GSE120721, GSE6012, GSE32924, and GSE153007 were downloaded from gene expression omnibus (GEO) database. The data of GSE120721 and GSE6012 were combined as the training group, while the others were served as the testing groups. Subsequently, the expression of PRGs was extracted from the training group and differentially expressed analysis was conducted. CIBERSORT algorithm calculated the immune cells infiltration and differentially expressed analysis was conducted. Consistent cluster analysis divided AD patients into different modules according to the expression levels of PRGs. Then, weighted correlation network analysis (WGCNA) screened the key module. For the key module, we used Random forest (RF), support vector machines (SVM), Extreme Gradient Boosting (XGB), and generalized linear model (GLM) to construct diagnostic models. For the five PRBMs with the highest model importance, we built a nomogram. Finally, the results of the model were validated using GSE32924, and GSE153007 datasets. RESULTS: Nine PRGs were significant differences in normal humans and AD patients. Immune cells infiltration showed that the activated CD4+ memory T cells and Dendritic cells (DCs) were significantly higher in AD patients than normal humans, while the activated natural killer (NK) cells and the resting mast cells were significantly lower in AD patients than normal humans. Consistent cluster analysis divided the expressing matrix into 2 modules. Subsequently, WGCNA analysis showed that the turquoise module had a significant difference and high correlation coefficient. Then, the machine model was constructed and the results showed that the XGB model was the optimal model. The nomogram was constructed by using HDAC1, GPALPP1, LGALS3, SLC29A1, and RWDD3 five PRBMs. Finally, the datasets GSE32924 and GSE153007 verified the reliability of this result. CONCLUSIONS: The XGB model based on five PRBMs can be used for the accurate diagnosis of AD patients.

Mechanism and Protective Effect of Smilax glabra Roxb on the Treatment of Heart Failure via Network Pharmacology Analysis and Vitro Verification.

Smilax glabra Roxb (SGR) has been widely applied alone or in combination with other Chinese herbs in heart failure (HF), but its mechanism and protective effect have not been investigated. We aimed to explore the mechanism and protective effect of SGR on the treatment of HF. Network pharmacology analysis predicted that SGR was involved in the regulation of cell proliferation, oxidation-reduction process, apoptotic process, ERK1 and ERK2 cascade, MAPK cascade, etc. Its mechanism was mainly involved in the MAPK signaling pathway, calcium signaling pathway, cardiac muscle contraction, etc. Subsequently, SGR was proved to improve cellular viability, restore cellular morphology, suppress cellular and mitochondrial ROS production, improve H2O2-induced lysosome inhibition, attenuate mitochondrial dysfunction, and protect mitochondrial respiratory and energy metabolism in H9c2 cells. SGR activated the p38MAPK pathway by decreasing the mRNA expression of AKT, PP2A, NF-KB, PP2A, RAC1, and CDC42 and increasing the mRNA expression of Jun, IKK, and Sirt1. SGR also decreased the protein expression of ERK1, ERK2, JNK, Bax, and Caspase3 and increased the protein expression of p38MAPK and Bcl-2. In addition, Istidina at the highest degree was identified in SGR via the UHPLCLTQ-Orbitrap-MSn method, and it was suggested as anti-heart failure agents by targeting SRC with molecular docking analysis. In conclusion, SGR has a protective effect on HF through cellular and mitochondrial protection via multi-compounds and multi-targets, and its mechanism is involved in activating the p38 MAPK pathway. Istidina may be possible anti-HF agents by targeting SRC.

Using human umbilical cord mesenchymal stem cells combined with allogenic platelet-rich fibrin membrane for the treatment of dual limb ischemia in an elderly patient: A case report.

RATIONALE: To describe the clinical effects of human umbilical cord mesenchymal stem cells (UCMSCs) combined with allogenic platelet-rich fibrin (PRF) for the treatment of lower limb ischemia in an elderly patient. PATIENT CONCERNS: The patient was a 93-year-old Chinese woman with bilateral foot gangrene and ulcers lasting for 6 months. She had a prior history of Behcet's disease. DIAGNOSES: The admitting diagnosis for this episode was atherosclerosis bilateral limb ischemia. INTERVENTIONS: First, treatment consisting of immunosuppressants, anticoagulation, antiplatelets, and anti-microbials were instituted. A UCMSC suspension was administered intravenously and injected into the lower limbs twice. An allogenic PRF membrane was externally applied 15 times over the lower limbs. OUTCOMES: The patient's pain improved and the 6 ulcers healed. LESSONS: The combination of UCMSCs with a PRF membrane for the treatment of lower limb ischemia in an elderly patient is effective and safe. More and larger trials are needed before incorporating this therapy into mainstream treatment.