Characterization of Cancer Cell Mechanics by Measuring Active Deformation Behavior.

Active deformation behavior reflects cell structural dynamics adapting to varying environmental constraints during malignancy progression. In most cases, cell mechanics is characterized by modeling using static equilibrium systems, which fails to comprehend cell deformation behavior leading to inaccuracies in distinguishing cancer cells from normal cells. Here, a method is introduced to measure the active deformation behavior of cancer cells using atomic force microscopy (AFM) and the newly developed deformation behavior cytometry (DBC). During the measurement, cells are deformed and allows a long timescale relaxation (≈5 s). Two parameters are derived to represent deformation behavior: apparent Poisson's ratio for adherent cells, which is measured with AFM and refers to the ratio of the lateral strain to the longitudinal strain of the cell, and shape recovery for suspended cells, which is measured with DBC. Active deformation behavior defines cancer cell mechanics better than traditional mechanical parameters (e.g., stiffness, diffusion, and viscosity). Additionally, aquaporins are essential for promoting the deformation behavior, while the actin cytoskeleton acts as a downstream effector. Therefore, the potential application of the cancer cell active deformation behavior as a biomechanical marker or therapeutic target in cancer treatment should be evaluated.

Interstitial Injection of Hydrogels with High-Mechanical Conductivity Relieves Muscle Atrophy Induced by Nerve Injury.

Injectable hydrogels have been extensively used in tissue engineering where high mechanical properties are key for their functionality at sites of high physiological stress. In this study, an injectable, conductive hydrogel is developed exhibiting remarkable mechanical strength that can withstand a pressure of 500 kPa (85% deformation rate) and display good fatigue resistance, electrical conductivity, and tissue adhesion. A stable covalent cross-linked network with a slip-ring structure by threading amino ß-cyclodextrin is formed onto the chain of a four-armed (polyethylene glycol) amino group, and then reacted with the four-armed (polyethylene glycol) maleimide under physiological conditions. The addition of silver nanowires enhances the hydrogel's electrical conductivity, enabling it to act as a good conductor in vivo. The hydrogel is injected into the fascial space, and the results show that the weight and muscle tone of the atrophied gastrocnemius muscle improve, subsequently alleviating muscle atrophy. Overall, this study provides a simple method for the preparation of a conductive hydrogel with high mechanical properties. In addition, the interstitial injection provides a strategy for the use of hydrogels in vivo.

Hydroxysafflor Yellow A Phytosomes Administered via Intervaginal Space Injection Ameliorate Pulmonary Fibrosis in Mice.

Idiopathic pulmonary fibrosis is a fatal interstitial disease characterized by fibroblast proliferation and differentiation and abnormal accumulation of extracellular matrix, with high mortality and an increasing annual incidence. Since few drugs are available for the treatment of pulmonary fibrosis, there is an urgent need for high-efficiency therapeutic drugs and treatment methods to reduce the mortality associated with pulmonary fibrosis. The interstitium, a highly efficient transportation system that pervades the body, plays an important role in the occurrence and development of disease, and can be used as a new route for disease diagnosis and treatment. In this study, we evaluated the administration of hydroxysafflor yellow A phytosomes via intervaginal space injection (ISI) as an anti-pulmonary fibrosis treatment. Our results show that this therapeutic strategy blocked the activation of p38 protein in the MAPK-p38 signaling pathway and inhibited the expression of Smad3 protein in the TGF-ß/Smad signaling pathway, thereby reducing secretion of related inflammatory factors, deposition of collagen in the lungs of mice, and destruction of the alveolar structure. Use of ISI in the treatment of pulmonary fibrosis provides a potential novel therapeutic modality for the disease.

Rapamycin nanoparticles improves drug bioavailability in PLAM treatment by interstitial injection.

BACKGROUND: Pulmonary lymphangiomyomatosis (PLAM) is a rare interstitial lung disease characterized by diffuse cystic changes caused by the destructive proliferation of smooth muscle-like cells or LAM cells. PLAM is more common in young women than other people, and a consensus is lacking regarding PLAM treatment. The clinical treatment of PLAM is currently dominated by rapamycin. By inhibiting the mTOR signaling pathway, rapamycin can inhibit and delay PLAM's occurrence and development. However, the application of rapamycin also has shortcomings, including the drug's low oral bioavailability and a high binding rate to hemoglobin, thus significantly decreasing the amount of drug distributed to the lungs. METHODS AND RESULTS: Here, we developed a new mode of rapamycin administration in which the drug was injected into the intrathecal space after being nanosized; the directional flow characteristics of the liquid in the intrathecal space were exploited to increase the drug content in the interstitial fluid to the greatest extent possible. We studied the rapamycin content in the interstitial fluid and blood after intervaginal space injection (ISI). Compared with oral administration, ISI significantly increased the drug concentration in the lung interstitial fluid. CONCLUSIONS: These results provided new ideas for treating PLAM and optimizing the dosing regimens of drugs with similar characteristics to rapamycin.

Phloridzin Reveals New Treatment Strategies for Liver Fibrosis.

Liver fibrosis is an urgent public health problem which is difficult to resolve. However, various drugs for the treatment of liver fibrosis in clinical practice have their own problems during use. In this study, we used phloridzin to treat hepatic fibrosis in the CCl4-induced C57/BL6N mouse model, which was extracted from lychee core, a traditional Chinese medicine. The therapeutic effect was evaluated by biochemical index detections and ultrasound detection. Furthermore, in order to determine the mechanism of phloridzin in the treatment of liver fibrosis, we performed high-throughput sequencing of mRNA and lncRNA in different groups of liver tissues. The results showed that compared with the model group, the phloridzin-treated groups revealed a significant decrease in collagen deposition and decreased levels of serum alanine aminotransferase, aspartate aminotransferase, laminin, and hyaluronic acid. GO and KEGG pathway enrichment analysis of the differential mRNAs was performed and revealed that phloridzin mainly affects cell ferroptosis. Gene co-expression analysis showed that the target genes of lncRNA were obvious in cell components such as focal adhesions, intercellular adhesion, and cell-substrate junctions and in metabolic pathways such as carbon metabolism. These results showed that phloridizin can effectively treat liver fibrosis, and the mechanism may involve ferroptosis, carbon metabolism, and related changes in biomechanics.

A drug-free nanozyme for mitigating oxidative stress and inflammatory bowel disease.

Inflammatory bowel disease (IBD) is an incurable disease of the gastrointestinal tract with a lack of effective therapeutic strategies. The proinflammatory microenvironment plays a significant role in both amplifying and sustaining inflammation during IBD progression. Herein, biocompatible drug-free ceria nanoparticles (CeNP-PEG) with regenerable scavenging activities against multiple reactive oxygen species (ROS) were developed. CeNP-PEG exerted therapeutic effect in dextran sulfate sodium (DSS)-induced colitis murine model, evidenced by corrected the disease activity index, restrained colon length shortening, improved intestinal permeability and restored the colonic epithelium disruption. CeNP-PEG ameliorated the proinflammatory microenvironment by persistently scavenging ROS, down-regulating the levels of multiple proinflammatory cytokines, restraining the proinflammatory profile of macrophages and Th1/Th17 response. The underlying mechanism may involve restraining the co-activation of NF-κB and JAK2/STAT3 pathways. In summary, this work demonstrates an effective strategy for IBD treatment by ameliorating the self-perpetuating proinflammatory microenvironment, which offers a new avenue in the treatment of inflammation-related diseases.

Clinical effect observation of Nd: YAG laser combined with acyclovir in the treatment of herpes labialis / 口腔疾病防治

Objective@#To investigate the clinical efficacy of Nd: YAG laser combined with 3% acyclovir cream in the treatment of herpes labialis. @* Methods @# A total of 72 patients with herpes labialis were enrolled. According to the random number table method, the patients were divided into an observation group and a control group with 36 patients in the observation group and 36 patients in the control group. The Nd: YAG laser combined with 3% acyclovir cream was administered to the observation group, while 3% acyclovir cream was administered to the control group. The total effective rate, scab, scab removal, analgesic time, and quality of life were compared between the two groups.@*Results@# 7 days after treatment, the total effective rate of clinical treatment in the control group was 27 patients (75%), and that in the observation group was 34 patients (94.4%); the contrast difference was statistically significant (P < 0.05). Compared with those in the control group, the crusting, prolapse and analgesic time of the observation group were shorter, and the differences were statistically significant (P < 0.05). Compared with the control group, the observation group had higher quality of life scores, and there was a statistical significance (P < 0.05). @*Conclusion @#For patients with herpes labialis, using Nd: YAG laser combined with 3% acyclovir cream treatment can significantly improve the quality of life of patients and accelerate the speed of patient rehabilitation.

Enhanced activation of persulfate by Fe(III) and catechin without light: Reaction kinetics, parameters and mechanism.

An environmental-friendly plant polyphenol, catechin (CAT), was applied in Fe(III) activated persulfate (PS) system for naproxen (NPX) degradation in this research. Reaction kinetics, parameters, NPX degradation products and reaction mechanism were investigated. Combining the results of quenching experiments as well as Electron Spin Resonance (ESR), it was observed that SO4•- was critical in NPX degradation, and the contribution of HO• was minor in the Fe(III)/CAT/PS system. O2•- was generated during the reaction but did not contribute to NPX degradation. SO4•- and HO• were produced from the PS activation by Fe(II), which was formed from the transient complexing and reduction process between Fe(III) and CAT. The effects of Fe(III), CAT, PS concentration and pH value on NPX degradation were evaluated. Moreover, the mineralization rate was 20.2%, and the toxicity of the treated solution were lower than the initial solution. Nine possible intermediates were determined when using LC-QTOF-MS to analyze, and three degradation pathways were put ward. The results proved that CAT could accelerate the redox cycle of Fe(III)/Fe(II), consequently to strengthen PS activation without light. It was a promising oxidation technology as it offered an energy-saving and hypo-toxic way for refractory organic pollutants treatment, and it was applicable at a comparatively wide pH range.

Activation of peroxymonosulfate by BiOCl@Fe3O4 catalyst for the degradation of atenolol: Kinetics, parameters, products and mechanism.

BiOCl@Fe3O4 photocatalyst was synthesized to activate peroxymonosulfate (PMS) for atenolol (ATL) degradation under simulated sunlight irradiation in present study. XRD, SEM, adsorbability and pore size distribution of BiOCl@Fe3O4 were analyzed. Magnetic BiOCl performed high activity in PMS activation and could be easily solid-liquid separation by applying an external magnetic field. Many parameters were inspected, including scavengers, PMS concentration, catalyst dosage, pH, anions (Cl- and CO3-). h+, SO4-, HO, O2-, SO5- were involved in ATL degradation in BiOCl@Fe3O4/PMS/sunlight system. The second-order rate constant of the reaction between ATL and SO4- (kATL, SO4-) was estimated via laser flash photolysis experiments. Moreover, ATL mineralization was followed by TOC analyzer. Twelve possible intermediate products were identified through LC-QTOF-MS analysis, and six ATL degradation pathways were concluded. This type of magnetic photocatalyst is characterized by ease of separation, high activation and good reusability. It may have application potential in refractory organic pollutants degradation.

[Effects of sleep deprivation induced blood stasis syndrome on platelet activation in rats].

Blood stasis syndrome is the pre-state of thrombotic disease. The model of blood stasis syndrome in rats was induced by sleep deprivation to study on effects of blood stasis syndrome on platelet activation. The weight, the color of tongue and hemorheology for the blood stasis syndrome of Chinese medicine were measured after modeling. The release of platelet granules and platelet activation factors in plasma were detected by ELISA kit related indicators to provide experimental basis for platelet function evaluation and related drug effects in syndrome research. The results showed that the weight of the model group rats was significantly lower than that of the normal group (P<0.01). The tongue showed a dark purple blood stasis pattern, and the R, G and B values of the tongue surface in model group were significantly lower than those of the normal group (P<0.01). The hemorheological parameters including high shear, middle shear and low shear viscosity in whole blood were significantly higher than those in the normal group (P<0.01). But plasma viscosity did not change significantly. The release levels of platelet α particles (GMP-140, ß-TG, PF4) and dense particles (ADP, 5-HT) were significantly higher than those in the normal group (P<0.01). The levels of TXB2 and 6-keto-PGF1α in plasma were significantly higher than those in the normal group (P<0.01). The ratios of TXB2 and 6-keto-PGF2α were also significantly higher than those in the normal group (P<0.01). The levels of PAF in plasma in model group were significantly higher than those in the normal group (P<0.01). It was concluded that platelet functions could be changed induced by sleep deprivationin rats with blood stasis syndrome, and there might be inflammation and endothelial cell dysfunction.

Degradation of atenolol via heterogeneous activation of persulfate by using BiOCl@Fe3O4 catalyst under simulated solar light irradiation.

Efficient oxidative degradation of pharmaceutical pollutants in aquatic environments is of great importance. This study used magnetic BiOCl@Fe3O4 catalyst to activate persulfate (PS) under simulated solar light irradiation. This degradation system was evaluated using atenolol (ATL) as target pollutant. Four reactive species were identified in the sunlight/BiOCl@Fe3O4/PS system. The decreasing order of the contribution of each reactive species on ATL degradation was as follows: h+ ≈ HO· > O2·- > SO4·-. pH significantly influenced ATL degradation, and an acidic condition favored the reaction. High degradation efficiencies were obtained at pH 2.3-5.5. ATL degradation rate increased with increased catalyst and PS contents. Moreover, ATL mineralization was higher in the sunlight/BiOCl@Fe3O4/PS system than in the sunlight/BiOCl@Fe3O4 or sunlight/PS system. Nine possible intermediate products were identified through LC-MS analysis, and a degradation pathway for ATL was proposed. The BiOCl@Fe3O4 nanomagnetic composite catalyst was synthesized in this work. This catalyst was easily separated and recovered from a treated solution by using a magnet, and it demonstrated a high catalytic activity. Increased amount of the BiOCl@Fe3O4 catalyst obviously accelerated the efficiency of ATL degradation, and the reusability of the catalyst allowed the addition of a large dosage of BiOCl@Fe3O4 to improve the degradation efficiency.