Cdc42-Interacting Protein-4 Promotes TGF-Β1-Induced Epithelial-Mesenchymal Transition and Extracellular Matrix Deposition in Renal Proximal Tubular Epithelial Cells

Cdc42-interacting protein-4 (CIP4) is an F-BAR (Fer/CIP4 and Bin, amphiphysin, Rvs) family member that regulates membrane deformation and endocytosis, playing a key role in extracellular matrix (ECM) deposition and invasion of cancer cells. These processes are analogous to those observed during the initial epithelial-mesenchymal transition (EMT) of renal tubular epithelial cells. The role of CIP4 in renal tubular EMT and renal tubulointerstitial fibrosis was investigated over the course of the current study, demonstrating that the expression of CIP4 increased in the tubular epithelia of 5/6-nephrectomized rats and TGF-β1 treated HK-2 cells. Endogenous CIP4 evidenced punctate localization throughout the cytosol, with elevated levels observed in the perinuclear region of HK-2 cells. Subsequent to TGF-β1 treatment, CIP4 expression increased, forming clusters at the cell periphery that gradually redistributed into the cytoplasm. Simultaneously, EMT induction in cells was confirmed by the prevalence of morphological changes, loss of E-cadherin, increase in α-SMA expression, and secretion of fibronectin. Overexpression of CIP4 promoted characteristics similar to those commonly observed in EMT, and small interfering RNA (siRNA) molecules capable of CIP4 knockdown were used to demonstrate reversed EMT. Cumulatively, results of the current study suggest that CIP4 promotes TGF-β1-induced EMT in tubular epithelial cells. Through this mechanism, CIP4 is capable of inducing ECM deposition and exacerbating progressive fibrosis in chronic renal failure

Oxidative Stress in Radiation-Induced Cardiotoxicity

There is a distinct increase in the risk of heart disease in people exposed to ionizing radiation (IR). Radiation-induced heart disease (RIHD) is one of the adverse side effects when people are exposed to ionizing radiation. IR may come from various forms, such as diagnostic imaging, radiotherapy for cancer treatment, nuclear disasters, and accidents. However, RIHD was mainly observed after radiotherapy for chest malignant tumors, especially left breast cancer. Radiation therapy (RT) has become one of the main ways to treat all kinds of cancer, which is used to reduce the recurrence of cancer and improve the survival rate of patients. The potential cause of radiation-induced cardiotoxicity is unclear, but it may be relevant to oxidative stress. Oxidative stress, an accumulation of reactive oxygen species (ROS), disrupts intracellular homeostasis through chemical modification and damages proteins, lipids, and DNA; therefore, it results in a series of related pathophysiological changes. The purpose of this review was to summarise the studies of oxidative stress in radiotherapy-induced cardiotoxicity and provide prevention and treatment methods to reduce cardiac damage

Analysis of the gas states at a liquid/solid interface based on interactions at the microscopic level

The states of gas accumulated at the liquid/solid interface are analyzed on the basis of the continuum theory, in which the Hamaker constant is used to describe the long-range interaction at the microscopic scale. The Hamaker constant is always negative, whereas the 'gas' spreading coefficient can be either negative or positive. Despite the complexity of gas, including that the density profile may not be uniform due to absorption on both solid and liquid surfaces, we predict three possible gas states at the liquid/solid interface, that is, complete 'wetting', partial 'wetting', and pseudopartial 'wetting'. These possible gas states correspond, respectively, to a gas pancake (or film) surrounded by a wet solid, a gas bubble with a finite contact angle, and a gas bubble(s) coexisting with a gas pancake. The typical thickness of the gas pancakes is at the nano scale within the force range of the long-range interaction, whereas the radius of the gas bubbles can be large. The state of a gas bubble(s) coexisting with a gas film is predicted theoretically for the first time. Our theoretical results can contribute to the development of a unified picture of gas nucleation at the liquid/solid interface

In silico and in vitro evaluation of antiviral activity of wogonin against main protease of porcine epidemic diarrhea virus

The high mortality rate of weaned piglets infected with porcine epidemic diarrhea virus (PEDV) poses a serious threat to the pig industry worldwide, demanding urgent research efforts related to developing effective antiviral drugs to prevent and treat PEDV infection. Small molecules can possibly prevent the spread of infection by targeting specific vital components of the pathogen’s genome. Main protease (Mpro, also named 3CL protease) plays essential roles in PEDV replication and has emerged as a promising target for the inhibition of PEDV. In this study, wogonin exhibited antiviral activity against a PEDV variant isolate, interacting with the PEDV particles and inhibiting the internalization, replication and release of PEDV. The molecular docking model indicated that wogonin was firmly embedded in the groove of the active pocket of Mpro. Furthermore, the interaction between wogonin and Mpro was validated in silico via microscale thermophoresis and surface plasmon resonance analyses. In addition, the results of a fluorescence resonance energy transfer (FRET) assay indicated that wogonin exerted an inhibitory effect on Mpro. These findings provide useful insights into the antiviral activities of wogonin, which could support future research into anti-PEDV drugs.

Soil gas CO2 emissions from active faults: a case study from the Anninghe—Zemuhe fault, Southeastern Tibetan Plateau, China

Introduction: Carbon dioxide emissions from non-volcanic areas are undervalued in the carbon cycle.Methods: First estimates of diffuse CO2 flux from the Anninghe—Zemuhe fault (AZF), Southeastern Tibetan Plateau, China, which suggests this could equal 15% emissions from all volcanoes in China. Following the accumulation chamber method, CO2 flux was investigated at 1,483 points, and along 67 profiles crossing the AZF. Results and discussion: Total CO2 emissions from the AZF were estimated 1.2 Mt yr-1. The relationship between soil gas CO2 fluxes, earthquakes, and fault activity was discussed. The intense fault activity in the southern part of the Zemuhe fault (ZMHF) and the northern part of the Anninghe fault (ANH) was inferred, which could have enhanced the porosity of the soil, and accelerated the water-rock interactions and soil gas emission within the fault zone. The chemical and isotopic data indicated that biogenic CO2 was the primary source of CO2 from the AZF. Produced by interactions between groundwaters and carbonates, soil gas CO2 could migrate to the near surface through cracks. Spatial variations of CO2 flux in soil gas indicate that seismic activity could be responsible for the jumpy variations of CO2 flux. The diffuse CO2 from deep faults may contribute considerably to the greenhouse gas cycles