Suppression of FPR2 expression inhibits inflammation in preeclampsia by improving the biological functions of trophoblast via NF-κB pathway

Purpose The dysfunction of trophoblast during inflammation plays an important role in PE. Formyl peptide receptor 2 (FPR2) plays crucial roles in the development of inflammation-associated disease. This present study aimed to explore the effect of FPR2 on a trophoblast cellular model of preeclampsia. Methods The expression of FPR2 in placenta was detected by immunohistochemical staining and western blotting. Transfection of siRNA was used to knockdown FPR2 in HTR-8/SVneo cells. Inflammatory cytokines were detected by ELISA. CCK8, Transwell, wound healing, FACS and tube formation assays were performed to observe the abilities of cell proliferation, migration, invasion, apoptosis and angiogenesis. Western blotting was implemented to clarify that NF-κB signaling pathway was downstream of FPR2. Results The expression levels of FPR2 were higher in placental tissues of patients with PE. Knockdown of FPR2 expression by siFPR2 or inhibition of its activity by WRW4 decreased the release of proinflammatory cytokines in HTR8/SVneo cells treated with LPS. Knockdown of FPR2 expression or inhibition of its activity further reversed the LPS-induced attenuation of the proliferation, migration, invasion and angiogenesis and increase in apoptosis in HTR8/SVneo cells. Moreover, the NF-κB signaling pathway was activated in both placental tissues of patients with PE and LPS-treated HTR8/SVneo cells. However, the activation was attenuated when FPR2 was knocked down or inhibited. Conclusion Suppression of FPR2 expression alleviated the effects of inflammation induced by LPS on trophoblasts via the NF-κB signaling pathway, which provided a novel and potential strategy for the treatment of PE.

NOG-Derived Peptides Can Restore Neuritogenesis on a CRASH Syndrome Cell Model

Homo- and heterophilic binding mediated by the immunoglobulin (Ig)-like repeats of cell adhesion molecules play a pivotal role in cell-cell and cell-extracellular matrix interactions. L1CAM is crucial to neuronal differentiation, in both mature and developing nervous systems, and several studies suggest that its functional interactions are mainly mediated by Ig2–Ig2 binding. X-linked mutations in the human L1CAM gene are summarized as L1 diseases, including the most diagnosed CRASH neurodevelopmental syndrome. In silico simulations provided a molecular rationale for CRASH phenotypes resulting from mutations I179S and R184Q in the homophilic binding region of Ig2. A synthetic peptide reproducing such region could both mimic the neuritogenic capacity of L1CAM and rescue neuritogenesis in a cellular model of the CRASH syndrome, where the full L1CAM ectodomain proved ineffective. Presented functional evidence opens the route to the use of L1CAM-derived peptides as biotechnological and therapeutic tools.

Inhibitory activity of flavonoids against human sucrase-isomaltase (α-glucosidase) activity in a Caco-2/TC7 cellular model

Flavonoids may be effective inhibitors of SI in Caco-2/TC7 cells when using natural substrates maltose and sucrose. The chemical features that favor the SI inhibition by flavonoids are the presence of –OH groups at C-3, C-3′, C-4′, C-7 and C-8.

DEVELOPMENT OF A MATHEMATICAL MODEL OF LIVER FILTRATION

Клетки печени занимают центральное место в реакциях промежуточного метаболизма. Печень принимает участие в метаболизме почти всех классов веществ. Основной структурной единицей печени является печеночная долька, которая представляет собой призму размером 1,5-2 мм с плоскими основанием и вершиной. По всей дольке также распределены лимфатические сосуды, которые активно поглощают интерстициальную жидкость и выводят ее с регулируемой скоростью, однако зависимость скорости поглощения от интерстициального давления и других параметров известна не полностью. В работе представлена математическая модель для оценки кровотока в печеночной дольке. Рассмотренная клеточная модель включает в себя производство и прохождение лимфы по двум основным путям: поглощение лимфатическими сосудами и выход из печени через поверхность дольки в интерстициальное пространство. Приведены геометрические и механические допущения модели и ее недостатки. В биологической модели исследовано влияние изменений кровяного давления в печени на выработку лимфы и оценивается скорость поглощения лимфы и поток жидкости (как лимфы, так и крови) по всей поверхности печени. В математической модели показана классификация: статическая (не зависящая от времени), пространственная, детерминированная, нелинейная, непрерывная. Результаты исследования показали, что предлагаемая клеточная модель микроциркуляции печени включает в себя производство и прохождение лимфы по двум основным путям: поглощение лимфатическими сосудами и выход из печени через поверхность дольки в интерстициальное пространство. Выявлены основные недостатки разрабатываемой модели Liver cells are central to intermediate metabolic reactions. The liver is involved in the metabolism of almost all classes of substances. The main structural unit of the liver is the hepatic lobule, which is a prism 1.5-2 mm in size with a flat base and apex. Lymphatic vessels are also distributed throughout the lobule, which actively absorb interstitial fluid and remove it at a controlled rate, however, the dependence of the rate of absorption on interstitial pressure and other parameters is not fully known. The paper presents a mathematical model for assessing blood flow in the hepatic lobule. The considered cellular model includes the production and passage of lymph through two main pathways: absorption by the lymphatic vessels and exit from the liver through the surface of the lobule into the interstitial space. Geometric and mechanical assumptions of the model and its disadvantages are presented. A biological model investigates the effect of changes in liver blood pressure on lymph production and estimates the rate of lymph absorption and fluid flow (both lymph and blood) over the entire surface of the liver. The mathematical model shows the classification: static (independent of time), spatial, deterministic, nonlinear, continuous. The results of the study showed that the proposed cellular model of liver microcirculation includes the production and passage of lymph through two main pathways: absorption by the lymphatic vessels and exit from the liver through the surface of the lobule into the interstitial space. The main shortcomings of the developed model are revealed

Synaptic memory requires CaMKII

Long-term potentiation (LTP) is arguably the most compelling cellular model for learning and memory. While the mechanisms underlying the induction of LTP ('learning') are well understood, the maintenance of LTP ('memory') has remained contentious over the last 20 years. Here, we find that CaMKII contributes to synaptic transmission and is required LTP maintenance. Acute inhibition of CaMKII erases LTP and transient inhibition of CaMKII enhances subsequent LTP. These findings strongly support the role of CaMKII as a molecular storage devise.

808-nm Photobiomodulation Affects the Viability of a Head and Neck Squamous Carcinoma Cellular Model, Acting on Energy Metabolism and Oxidative Stress Production

Photobiomodulation (PBM) is a form of low-dose light therapy that acts through energy delivery from non-ionizing sources. During the recent two decades, there has been tremendous progress with PBM acceptance in medicine. However, PBM effects on potential stimulation of existing malignant or pre-malignant cells remain unknown. Thus, the primary endpoint was to assess the safety of PBM treatment parameters on head and neck squamous cell carcinoma (HNSCC) proliferation or survival. The secondary endpoint was to assess any putative anti-cancer effects of PBM treatments. Cell viability, energy metabolism, oxidative stress, and pro- and anti-apoptotic markers expression were investigated on a Human Head and Neck Squamous Cell Carcinoma cellular model (OHSU-974 FAcorr cell line). PBM therapy was administered through the 810 nm diode laser (GaAlAs) device (Garda Laser, 7024 Negrar, Verona, Italy) at the powers of 0, 0.25, 0.50, 0.75, 1.00, or 1.25 W in continuous wave (CW) mode for an exposure time of 60 s with a spot-size of 1 cm2 and with a distance of 1.86 cm from the cells. Results showed that 810-nm PBM affected oxidative phosphorylation in OHSU-971 FAcorr, causing a metabolic switch to anaerobic glycolysis. In addition, PBM reduced the catalase activity, determining an unbalance between oxidative stress production and the antioxidant defenses, which could stimulate the pro-apoptotic cellular pathways. Our data, at the parameters investigated, suggest the safeness of PBM as a supportive cancer therapy. Pre-clinical and clinical studies are necessary to confirm the in vitro evidence.

Underlying Mechanism and Active Ingredients of Tianma Gouteng Acting on Cerebral Infarction as Determined via Network Pharmacology Analysis Combined With Experimental Validation

Cerebral infarction (CI), a common cerebrovascular disease worldwide, is caused by unknown factors common to many diseases, including hypokalemia, respiratory diseases, and lower extremity venous thrombosis. Tianma Gouteng (TMGT), a traditional Chinese Medicine (TCM) prescription, has been used for the clinical treatment of CI. In this study, high-performance liquid chromatography (HPLC) fingerprint analysis was used to detect and identify major chemical constituents of TMGT. TCMSP and BATMAN-TCM databases were used to screen for active TMGT constituent compounds, while the GeneCards database was used to screen for protein targets associated with CI. Next, GO and KEGG enrichment analysis of these core nodes were performed to determine the identities of key associated biological processes and signal pathways. Meanwhile, a total of six possible gene targets of TMGT, including NFKBIA, PPARG, IL6, IL1B, CXCL8, and HIF1A, were selected for further study using two cellular models of CI. For one model, PC12 cells were treated under oxygen and glucose deprivation (OGD) conditions to generate an OGD cellular model of CI, while for the other model, BV2 cells were stimulated with lipopolysaccharide (LPS) to generate a cellular model of CI-associated inflammation. Ultimately TMGT treatment increased PPARγ expression and downregulated the expression of p-P65, p-IκBα, and HIF-1α in both OGD-induced and LPS-induced cell models of CI. In addition, molecular docking analysis showed that one TMGT chemical constituent, quercetin, may be a bioactive TMGT compound with activity that may be associated with the alleviation of neuronal damage and neuroinflammation triggered by CI. Moreover, additional data obtained in this work revealed that TMGT could inhibit neuroinflammation and protect brain cells from OGD-induced and LPS-induced damage by altering HIF-1α/PPARγ/NF-κB pathway functions. Thus, targeting this pathway through TMGT administration to CI patients may be a strategy for alleviating nerve injury and neuroinflammation triggered by CI.

Wetting between Cassie–Baxter and Wenzel regimes: a cellular model approach

The cellular model with periodic boundary conditions was proposed for the study of liquid–solid interface properties of solid surfaces decorated by a regular pattern. The solid surface was represented by a mosaic of truncated pyramids of two different slopes of side walls equivalent to a surface covered with triangular grooves of different dihedral angles. On the basis of the computations performed for a single elementary cell, the components of the interfacial energies and the apparent contact angles have been found for different Young contact angles and different tilting angles of the pyramid walls. It was found that at certain sets of angles, the wetting takes place with the partial coverage of the pyramid sidewalls—in between the Cassie–Baxter and Wenzel regimes. The influence of the line tension on the studied surface wettability was also examined. Graphic abstract