Long-acting bulleyaconitine A microspheres via intra-articular delivery for multidimensional therapy of rheumatoid arthritis.

Bulleyaconitine A (BLA) is a promising candidate for treating rheumatoid arthritis (RA) with diverse pharmacological activities, including anti-inflammatory, analgesic and bone repair. Herein, the long-acting bulleyaconitine A microspheres (BLA-MS) were developed to treat RA comprehensively by forming drug reservoirs in joint cavities. The BLA-MS were prepared by emulsion/solvent evaporation method. The particle size and distribution were assessed by SEM. The crystalline state was investigated by DSC and PXRD. The drug loading (DL), encapsulation efficiency (EE) and cumulative release in vitro were determined by HPLC. The DL and EE were 23.93 ± 0.38 % and 95.73 ± 1.56 % respectively, and the cumulative release was up to 69 days with a stable release curve. The pharmacodynamic results in collagen induced arthritis (CIA) rats showed a noticeable reduction in paw thickness (5.66 ± 0.32 mm), and the decreasing expression level of PGE2, TNF-α and IL-6 which diminished the infiltration of inflammatory cells, thereby alleviating the progression of erosion and repairing the damaged bones (BV/TV (Bone Volume / Total Volume): 81.97 %, BS/BV (Bone Surface / Bone Volume): 6.08 mm-1). In conclusion, intra-articular injection of BLA-MS should have a promising application in the treatment of RA and may achieve clinical transformation in the future.

An adaptive drug-releasing contact lens for personalized treatment of ocular infections and injuries.

This research introduces an innovative solution to address the challenges of bacterial keratitis and alkali burns. Current treatments for bacterial keratitis and alkali burns rely on the frequent use of antibiotics and anti-inflammatory eye drops. However, these approaches suffer from poor bioavailability and fluctuating concentrations, leading to limited efficacy and potential drug resistance. Our approach presents an adaptive drug-releasing contact lens responsive to reactive oxygen species (ROS) at ocular inflammation sites, synchronously releasing Levofloxacin and Diclofenac. During storage, minimal drug release occurred, but over 7 days of wear, the lens maintained a continuous, customizable drug release rate based on disease severity. This contact lens had strong antibacterial activity and biofilm prevention, effectively treating bacterial keratitis. When combined with autologous serum, this hydrophilic, flexible lens aids corneal epithelial regeneration, reducing irritation and promoting healing. In summary, this ROS-responsive drug-releasing contact lens combines antibacterial and anti-inflammatory effects, offering a promising solution for bacterial keratitis and alkali burns.

Structure-based prediction of protein-protein interaction network in rice.

Comprehensive protein-protein interaction (PPI) maps are critical for understanding the functional organization of the proteome, but challenging to produce experimentally. Here, we developed a computational method for predicting PPIs based on protein docking. Evaluation of performance on benchmark sets demonstrated the ability of the docking-based method to accurately identify PPIs using predicted protein structures. By employing the docking-based method, we constructed a structurally resolved PPI network consisting of 24,653 interactions between 2,131 proteins, which greatly extends the current knowledge on the rice protein-protein interactome. Moreover, we mapped the trait-associated single nucleotide polymorphisms (SNPs) to the structural interactome, and computationally identified 14 SNPs that had significant consequences on PPI network. The protein structural interactome map provided a resource to facilitate functional investigation of PPI-perturbing alleles associated with agronomically important traits in rice.

CT radiomics to differentiate between Wilms tumor and clear cell sarcoma of the kidney in children.

BACKGROUND: To investigate the role of CT radiomics in distinguishing Wilms tumor (WT) from clear cell sarcoma of the kidney (CCSK) in pediatric patients. METHODS: We retrospectively enrolled 83 cases of WT and 33 cases of CCSK. These cases were randomly stratified into a training set (n = 81) and a test set (n = 35). Several imaging features from the nephrographic phase were analyzed, including the maximum tumor diameter, the ratio of the maximum CT value of the tumor solid portion to the mean CT value of the contralateral renal vein (CTmax/CT renal vein), and the presence of dilated peritumoral cysts. Radiomics features from corticomedullary phase were extracted, selected, and subsequently integrated into a logistic regression model. We evaluated the model's performance using the area under the curve (AUC), 95% confidence interval (CI), and accuracy. RESULTS: In the training set, there were statistically significant differences in the maximum tumor diameter (P = 0.021) and the presence of dilated peritumoral cysts (P = 0.005) between WT and CCSK, whereas in the test set, no statistically significant differences were observed (P > 0.05). The radiomics model, constructed using four radiomics features, demonstrated strong performance in the training set with an AUC of 0.889 (95% CI: 0.811-0.967) and an accuracy of 0.864. Upon evaluation using fivefold cross-validation in the training set, the AUC remained high at 0.863 (95% CI: 0.774-0.952), with an accuracy of 0.852. In the test set, the radiomics model achieved an AUC of 0.792 (95% CI: 0.616-0.968) and an accuracy of 0.857. CONCLUSION: CT radiomics proves to be diagnostically valuable for distinguishing between WT and CCSK in pediatric cases.

Inflammation-responsive molecular-gated contact lens for the treatment of corneal neovascularization.

Corneal neovascularization (CNV) badly damages the corneal transparency, resulting in visual disturbance and blindness. The frequent administration of glucocorticoid eye drops in clinical increases the possibility of side effects and reduces patient compliance. Considering CNV is often accompanied by an increase in ROS production, a ROS-responsive monomer 2-(methylthio)ethyl methacrylate was introduced into the matrix as a "gating switch". The prepared dexamethasone contact lenses (MCLs@Dex) showed a significant H2O2-responsive release for 168 h. To avoid corneal hypoxia and neovascularization caused by long-term wearing, high­oxygen-permeability fluorosiloxane materials were incorporated. The oxygen permeability of MCLs@Dex was 4 times that of commercially available hydrogel contact lenses and had ultra-low protein adsorption, which meets the requirements of long-term wearing. In vivo pharmacokinetic studies showed that MCLs@Dex increased the mean residence time by 19.7 times and bioavailability by 2.29 times compared with eye drops, validating the ROS response and sustained release properties. More importantly, MCLs@Dex had satisfactory effects on reducing inflammation and decreasing the related cytokines and oxidative stress levels, and demonstrated significant inhibition of neovascularization, with a suppression rate of 76.53% on the 14th day. This responsive drug delivery system provides a promising new method for the safe and effective treatment of ocular surface diseases.

2,2,2-Trifluoroethanol-Assisted Construction of 2D/3D Perovskite Heterostructures for Efficient and Stable Perovskite Solar Cells Made in Ambient Air.

To achieve future commercialization of perovskite solar cells (PSCs), balancing the efficiency, stability, and manufacturing cost is required. In this study, we develop an air processing strategy for efficient and stable PSCs based on 2D/3D heterostructures. The organic halide salt phenethylammonium iodide is adopted to in situ construct a 2D/3D perovskite heterostructure, in which 2,2,2-trifluoroethanol as a precursor solvent is introduced to recrystallize 3D perovskite and form an intermixed 2D/3D perovskite phase. This strategy simultaneously passivates defects, reduces nonradiative recombination, prevents carrier quenching, and improves carrier transport. As a result, a champion power conversion efficiency of 20.86% is obtained for air-processed PSCs based on 2D/3D heterostructures. Moreover, the optimized devices exhibit superior stability, remaining more than 91 and 88% of their initial efficiencies after 1800 h of storage under dark condition and 24 h of continuous heating at 100 °C, respectively. Our study provides a convenient method to fabricate all-air-processed PSCs with high efficiency and stability.

Self-Assembled 1D/3D Perovskite Heterostructure for Stable All-Air-Processed Perovskite Solar Cells with Improved Open-Circuit Voltage.

Environmental instability and photovoltage loss induced by defects are inevitable obstacles in the development of all-air-processed perovskite solar cells (PSCs). In this study, the ionic liquid 1-ethyl-3-methylimidazolium iodide ([EMIM]I) is introduced into the hole transport layer/three-dimensional (3D) perovskite interface to form a self-assembled 1D/3D perovskite heterostructure, which significantly reduces iodine vacancy defects and modulates band energy alignment, resulting in pronouncedly improved open-circuit voltage (Voc ). As a result, the corresponding device exhibits a high power conversion efficiency with negligible hysteresis and a high Voc of 1.14 V. Most importantly, together with the high stability of the 1D perovskite, remarkable high environmental and thermal stabilities of the 1D/3D PSC devices are achieved, which maintain 89 % of unencapsulated device initial efficiency after 1320 h in air and retain 85 % of the initial efficiency when heated at 85 °C for 22 h. This study affords an effective strategy to fabricate high-performance all-air-processed PSCs with outstanding stability.

Efficient decolorization of melanoidin in raw molasses wastewater by thermophilic esterase in actual extreme conditions.

This work was developed to explore the versatility of thermophilic esterase for decolorizing raw molasses wastewater at high temperature and acidic pH. Combining covalent crosslinking method with deep eutectic solvent, a thermophilic esterase from Pyrobaculum calidifontis was immobilized on chitosan/macroporous resin composite carrier. The application of this immobilized thermophilic esterase eliminated 92.35% of colorants in raw molasses wastewater, achieving maximal decolorization efficiency across all the enzymes tested. Strikingly, this immobilized thermophilic esterase was capable of engaging in continuous activity for a 5-day period while removing 76.23% of pigments from samples. It effectively and continuously eliminated BOD5 and COD, effectively and directly facilitating raw molasses wastewater decolorization under extreme conditions more readily than control group. In addition, this thermophilic esterase was believed to achieve decolorization through an addition reaction that disrupted conjugated system of melanoidins. Together, these results highlight an efficient and practical means of achieving enzyme-based molasses wastewater decolorization.

In situ rearranged multifunctional lipid nanoparticles via synergistic potentiation for oral insulin delivery.

Oral administration of therapeutic peptides/proteins (TPPs) is confronted with multiple gastrointestinal (GI) barriers such as mucus and intestinal epithelium, and the first-pass metabolism in the liver is also responsible for low bioavailability. In situ rearranged multifunctional lipid nanoparticles (LNs) were developed to overcome these obstacles via synergistic potentiation for oral insulin delivery. After the reverse micelles of insulin (RMI) containing functional components were gavaged, LNs formed in situ under the hydration effect of GI fluid. The nearly electroneutral surface generated by the rearrangement of sodium deoxycholate (SDC) and chitosan (CS) on the reverse micelle core facilitated LNs (RMI@SDC@SB12-CS) to overcome mucus barrier and the sulfobetaine 12 (SB12) modification further promoted epithelial uptake of LNs. Subsequently, chylomicron-like particles formed by the lipid core in the intestinal epithelium were easily transported to the lymphatic circulation and then into the systemic circulation, thus avoiding hepatic first-pass metabolism. Eventually, RMI@SDC@SB12-CS achieved a high pharmacological bioavailability of 13.7% in diabetic rats. In conclusion, this study provides a versatile platform for enhanced oral insulin delivery.

Protective effects of lycopene on TiO2 nanoparticle-induced damage in the liver of mice.

Titanium dioxide nanoparticles (nano-TiO2 ) is one of the most widely used and produced nanomaterials. Studies have demonstrated that nano-TiO2 could induce hepatotoxicity through oxidative stress, and lycopene has strong antioxidant capacity. The present study aimed to explore if lycopene protects the liver of mice from nano-TiO2 damage. Ninety-six ICR mice were randomly divided into eight groups. They were control group, nano-TiO2 -treated group (50 mg/kg BW), lycopene-treated groups (5, 20, and 40 mg/kg BW), and 50 mg/kg BW nano-TiO2 - and lycopene-co-treated groups (nano-TiO2 + 5 mg/kg BW of lycopene, nano-TiO2 + 20 mg/kg BW of lycopene, nano-TiO2 + 40 mg/kg BW of lycopene). After treated by gavage for 30 days, the histopathology of the liver was observed. Liver function was evaluated using changes in serum biochemical indicators of the liver (AST, ALT, ALP); and the level of ROS was indirectly reflected by the level of SOD, GSH-Px, MDA, GSH, and T-AOC. TUNEL assay was performed to examine the apoptosis of hepatocytes. Proteins of p53, cleaved-caspase 9, cleaved-caspase 3, Bcl-2, and Bax as well as p38 were detected. Results showed that lycopene alleviated the liver pathological damage and reduced the injury to liver function induced by nano-TiO2 , as well as decreased nano-TiO2 -induced ROS. Meanwhile, lycopene mitigated apoptosis resulting from nano-TiO2 , accompanied by the reversed expression of apoptosis-related proteins. Furthermore, lycopene significantly reversed the upregulation of p-p38 induced by nano-TiO2 . In conclusion, this study demonstrated that nano-TiO2 resulted in hepatocyte apoptosis through ROS/ROS-p38 MAPK pathway and led to liver function injury. Lycopene protected mice liver against the hepatotoxicity of nano-TiO2 through antioxidant property.

In Situ Regulation and Mechanisms of 3D Matrix Stiffness on the Activation and Reversion of Hepatic Stellate Cells.

Activated hepatic stellate cells (HSCs) is a key event in the progression of liver fibrosis. HSCs transdifferentiate into myofibroblasts and secrete large amounts of extracellular matrix, resulting in increased liver stiffness. It is difficult for platforms constructed in vitro to simulate the structure, composition, and stiffness of the 3D microenvironment of HSCs in vivo. Here, 3D scaffolds with different stiffness are constructed by decellularizing rat livers at different stages of fibrosis. The effects of matrix stiffness on the proliferation, activation, and reversion of HSCs are studied. The results demonstrate these scaffolds have good cytocompatibility. It is also found that the high stiffness can significantly promote the activation of HSCs, and this process is accompanied by the activation of integrin ß1 as well as the nucleation and activation of Yes-associated protein (YAP). Moreover, the low stiffness of the scaffold can promote the reversion of activated HSCs, which is associated with cell apoptosis and accompanied by the inactivation of integrin ß1 and YAP. These results suggest that YAP may be a potential therapeutic target for the treatment of liver fibrosis and the theoretical feasibility of inducing activated HSCs reversion to the resting state by regulating matrix stiffness of liver.

Effects of nano-titanium dioxide on calcium homeostasis in vivo and in vitro: a systematic review and meta-analysis.

With the extensive application of titanium dioxide nanoparticles (TiO2 NPs), their impacts on calcium homeostasis have aroused extensive attention from scholars. However, there are still some controversies in relevant reports. Therefore, a systematic review was performed followed by a meta-analysis to explore whether TiO2 NPs could induce the imbalance in calcium homeostasis in vivo and in vitro through Revman5.4 and Stata15.0 in this research. Fourteen studies were included through detailed database retrieval and literature screening. Results indicated that the calcium levels were significantly increased and the activity of Ca2+-ATPase was significantly decreased by TiO2 NPs in vivo and in vitro. Subgroup analysis of the studies in vivo showed that TiO2 NPs exposure caused a significant increase in calcium levels in rats, exposure to large-sized TiO2 NPs (>10 nm) and long-term (>30 days) exposure could significantly increase calcium levels, and the activity of Ca2+-ATPase showed a concentration-dependent downward trend. Subgroup analysis of the studies in vitro revealed that intracellular calcium levels increased significantly in animal cells, exposure to small-sized TiO2 NPs (≤10 nm) and high concentration (>10 µg/mL) exposure could induce a significant increase in Ca2+ concentration, and the activity of Ca2+-ATPase also showed a concentration-dependent downward trend. This research showed that the physicochemical properties of TiO2 NPs and the experimental scheme could affect calcium homeostasis.

Effects of post-fermentation on the flavor compounds formation in red sour soup.

Red Sour Soup (RSS) is a traditional fermented food in China. After two rounds of fermentation, sour soup has a mellow flavor. However, the microbial composition and flavor formation processes in post-fermentation in RSS are unclear. This study investigates the bacteria composition of RSS during the post-fermentation stage (0-180 days) using high-throughput sequencing. The results show that lactic acid bacteria (LAB) are dominant during the post-fermentation process, and their abundance gradually increases with fermentation time. Additionally, gas chromatography-mass spectrometry was used to detect volatile flavor compounds in the post-fermentation process. Seventy-seven volatile flavor compounds were identified, including 24 esters, 14 terpenes, 9 aromatic hydrocarbons, 9 alkanes, 6 heterocyclic compounds, 3 alcohols, 3 acids, 3 ketones, 2 phenols, 2 aldehydes, 1 amine, and 1 other. Esters and aromatic hydrocarbons are the main volatile compounds in RSS during the post-fermentation process. Orthogonal partial least squares screening and correlation analysis derived several significant correlations, including 48 pairs of positive correlations and 19 pairs of negative correlations. Among them, Acetobacter spp., Clostridium spp. and Sporolactobacillus spp. have 15, 14, 20 significant correlation pairs, respectively, and are considered the most important bacterial genera post-fermentation. Volatile substances become abundant with increasing fermentation time. LAB are excessive after more than 120 days but cause a drastic reduction in volatile ester levels. Thus, the post-fermentation time should be restricted to 120 days, which retains the highest concentrations of volatile esters in RSS. Overall, these findings provide a theoretical basis to determine an optimal post-fermentation time duration, and identify essential bacteria for manufacturing high-quality starter material to shorten the RSS post-fermentation processing time.

Effect of Titanium Dioxide Nanoparticles on Mammalian Cell Cycle In Vitro: A Systematic Review and Meta-Analysis.

Although most studies that explore the cytotoxicity of titanium dioxide nanoparticles (nano-TiO2) have focused on cell viability and oxidative stress, the cell cycle, a basic process of cell life, can also be affected. However, the results on the effects of nano-TiO2 on mammalian cell cycle are still inconsistent. A systematic review and meta-analysis were therefore performed in this research based on the effects of nano-TiO2 on the mammalian cell cycle in vitro to explore whether nano-TiO2 can induce cell cycle arrest. Meanwhile, the impact of physicochemical properties of nano-TiO2 on the cell cycle in vitro was investigated, and the response of normal cells and cancer cells was compared. A total of 33 articles met the eligibility criteria after screening. We used Review Manager 5.4 and Stata 15.1 for analysis. The results showed an increased percentage of cells in the sub-G1 phase and an upregulation of the p53 gene after being exposed to nano-TiO2. Nevertheless, nano-TiO2 had no effect on cell percentage in other phases of the cell cycle. Furthermore, subgroup analysis revealed that the cell percentage in both the sub-G1 phase of normal cells and S phase of cancer cells were significantly increased under anatase-form nano-TiO2 treatment. Moreover, nano-TiO2 with a particle size <25 nm or exposure duration of nano-TiO2 more than 24 h induced an increased percentage of normal cells in the sub-G1 phase. In addition, the cell cycle of cancer cells was arrested in the S phase no matter if the exposure duration of nano-TiO2 was more than 24 h or the exposure concentration was over 50 µg/mL. In conclusion, this study demonstrated that nano-TiO2 disrupted the cell cycle in vitro. The cell cycle arrest induced by nano-TiO2 varies with cell status and physicochemical properties of nano-TiO2.

Nanosized Titanium Dioxide Induced Apoptosis and Abnormal Expression of Blood-Testis Barrier Junction Proteins Through JNK Signaling Pathway in TM4 Cells.

Nanosized titanium dioxide (nano-TiO2) has been widely used in consumer products. It can cross the blood-testis barrier (BTB), and it has adverse effects on the male reproductive system. However, the specific mechanism has not been fully elucidated. The purpose of this study was to understand the role of the JNK signaling pathway in the apoptosis and abnormal expression of BTB junction proteins induced by nano-TiO2 in TM4 cells. After different concentration of nano-TiO2 treatments, the cell viability, apoptosis, mitochondrial membrane potential (Δψm), BTB junction proteins (Claudin-11, ZO-1, ß-catenin), apoptosis-related proteins (Bax, Bcl-2, cleaved caspase-9, cleaved caspase-3), and phosphorylated (p)-JNK protein were examined. The results showed that cell viability, apoptosis rates, Δψm, and apoptosis-related protein levels changed in a concentration-dependent manner. Cell viability decreased significantly from 100 µg/mL nano-TiO2 group. Apoptosis rates increased significantly from 150 µg/mL nano-TiO2 group, and Δψm decreased significantly from 150 µg/mL nano-TiO2 group. The protein levels of Bax, cleaved caspase-9, and cleaved caspase-3 increased significantly from 150 µg/mL nano-TiO2 group, and the protein level of Bcl-2 decreased significantly from 100 µg/mL nano-TiO2 group. The protein level of p-JNK increased significantly from 100 µg/mL nano-TiO2 group. Abnormal expression of ZO-1 and ß-catenin started from 150 µg/mL nano-TiO2 group, and abnormal expression of Claudin-11 started from 100 µg/mL nano-TiO2 group. Cells were treated with JNK inhibitor SP100625 to determine whether the changes of the above indicators in the concentration of 150 µg/mL nano-TiO2 group can be reversed. We found that SP100625 at 20 µM significantly reversed these effects. These results highlighted that nano-TiO2 could activate the JNK signaling pathway to induce mitochondria-mediated apoptosis and abnormal expression of BTB junction proteins in TM4 cells.

Interface Chelation Induced by Pyridine-Based Polymer for Efficient and Durable Air-Processed Perovskite Solar Cells.

Polymer doping is a significant approach to precisely control nucleation and crystal growth of perovskites and enhance electronic quality in perovskite solar cells (PSC) prepared in air. Here, a brand-new self-healing polysiloxane (SHP) with dynamic 2,6-pyridinedicarboxamide (PDCA) coordination units and plenty of hydrogen bonds was designed and incorporated into perovskite films. PDCA units, showing strong intermolecular Pb2+ -Namido , I- -Npyridyl , and Pb2+ -Oamido coordination interactions, were expected to enhance crystallinity and passivate the grain boundary. In addition, abundant hydrogen bonds in SHP afforded the self-healing of cracks at grain boundaries for fatigue PSCs. Significantly, the doped device demonstrated a champion efficiency of 19.50 % with inconspicuous hysteresis, almost rivaling those achieved in control atmosphere. This strategy of heterocyclic-based macromolecular doping in PSCs will pave a way for realizing efficient and durable crystalline semiconductors.

Amino-Linked Conjugated Tetrazole Ring Passivation Strategy for Air-Processed Perovskite Cells with Predominant Stability and Efficiency.

Perovskite solar cells (PSCs) develop rapidly with certified efficiency over 25.5 %, but there are remaining problems such as defects-induced recombination and degradation throughout the whole device. Functional organic small molecule passivation strategies are diverse and efficient, enhancing the efficiency and stability of PSCs. Here, 5-aminotetrazole (5ATZ) was introduced for the first time as an effective passivator, where -NH2 and -NH as active sites interacted with the Pb and I related to vacancy defects in perovskites, anchoring defects and preventing further unavoidable ion migration and device degradation. Furthermore, the extensive π-electron delocalization around the tetrazole conjugated ring significantly promoted the charge transfer. Therefore, the 5ATZ-processed PSCs provided enhanced voltage and current, showed superior 19.75 % power conversion efficiency with excellent performance and improved stability, and demonstrated one of the best performances in all-air preparation to date. The simultaneous multi-effect passivation strategy of vacancy defects in perovskites will contribute to eliminate obstacles on the road to commercialization of PSCs.

Genotoxicity evaluation of silica nanoparticles in murine: a systematic review and meta-analysis.

Silica nanoparticles (SiNPs) have been widely used in nanotechnology, and more attention has been paid to their safety evaluation. However, there are still inconsistent conclusions about the genotoxicity of SiNPs. A systematic review was conducted to explore whether SiNPs have genotoxicity followed by a meta-analysis of in vivo and in vitro murine genotoxicity tests. A total of 26 eligible studies were identified in this meta-analysis through a detailed process of inclusion and exclusion, which included 9 in vivo studies, 15 in vitro studies, and 2 in both. The results of in vitro studies showed that SiNPs exposure significantly increased the indicators of the comet assay, such as tail DNA content (T DNA%), tail length (TL), and olive tail moment (OTM). Indicators of mutagenicity had not been affected in vitro studies, such as mutation frequency (MF) and micronucleus (MN) frequency. There was a significant increase in MN frequency, but there was no influence on T DNA% in vivo. Results of subgroup analysis indicated that size and treatment time of SiNPs were the associated factors in vitro genotoxicity. The size of SiNPs, <21 nm, induced more DNA damage than larger sized SiNPs. It could induce MN formation when the treatment time of SiNPs was <12 h, and even more DNA damage when the exposure time over 12 h. SiNPs can induce genotoxicity both in vivo and in vitro. Comet assay may be more sensitive to detect in vitro genotoxicity, and MN frequency may be more suitable to detect in vivo genotoxicity.

Stem Cell-based Therapy Strategy for Hepatic Fibrosis by Targeting Intrahepatic Cells.

The whole liver transplantation is the most effective treatment for end-stage fibrosis. However, the lack of available donors, immune rejection and total cost of surgery remain as the key challenges in advancing liver fibrosis therapeutics. Due to the multi-differentiation and low immunogenicity of stem cells, treatment of liver fibrosis with stem cells has been considered as a valuable new therapeutic modality. The pathological progression of liver fibrosis is closely related to the changes in the activities of intrahepatic cells. Damaged hepatocytes, activated Kupffer cells and other inflammatory cells lead to hepatic stellate cells (HSCs) activation, further promoting apoptosis of damaged hepatocytes, while stem cells can work on fibrosis-related intrahepatic cells through relevant transduction pathways. Herein, this article elucidates the phenomena and the mechanisms of the crosstalk between various types of stem cells and intrahepatic cells including HSCs and hepatocytes in the treatment of liver fibrosis. Then, the important influences of chemical compositions, mechanical properties and blood flow on liver fibrosis models with stem cell treatment are emphasized. Clinical trials on stem cell-based therapy for liver fibrosis are also briefly summarized. Finally, continuing challenges and future directions of stem cell-based therapy for hepatic fibrosis are discussed. In short, stem cells play an important advantage and have a great potential in treating liver fibrosis by interacting with intrahepatic cells. Clarifying how stem cells interact with intrahepatic cells to change the progression of liver fibrosis is of great significance for a deeper understanding of liver fibrosis mechanisms and targeted therapy.

Lycopene Alleviates Titanium Dioxide Nanoparticle-Induced Testicular Toxicity by Inhibiting Oxidative Stress and Apoptosis in Mice.

PURPOSE: The research was carried out to investigate the possible ameliorative effect of lycopene on TiO2 NPs-induced male reproductive toxicity and explore the possible mechanism. METHODS: Ninety-six healthy male Institute of Cancer Research (ICR) mice were equally divided into eight groups (control group, 50 mg/kg TiO2 NPs group, 5 mg/kg LYC group, 20 mg/kg LYC group, 40 mg/kg LYC group, 50 mg/kg TiO2 NPs + 5 mg/kg LYC group, 50 mg/kg TiO2 NPs + 20 mg/kg LYC group, 50 mg/kg TiO2 NPs + 40 mg/kg LYC group), and the mice were treated by intragastric administration every day for 30 days in this research. Sperm parameters, testicular histopathology, oxidant and antioxidant enzymes, and cell apoptosis-related protein expression in the testicular tissue were analyzed. RESULTS: The results showed that TiO2 NPs exposure significantly decreased sperm count and motility, and TiO2 NPs also increased sperm malformation in the epididymis; these characteristics were improved when co-administration with LYC. Testicular histopathological lesions like disorder of germ cells arrange, detachment, atrophy, and vacuolization were observed after TiO2 NPs exposure, and these abnormalities were effectively ameliorated by co-administration with LYC. Oxidative stress was induced by TiO2 NPs exposure as evidenced by increased the level of MDA and decreased the activity of SOD as well as the level of anti-O2-, and these alterations were effectively prevented by co-administration with LYC. LYC also alleviated TiO2 NPs-induced germ cell apoptosis by inhibiting mitochondrial apoptotic pathway, as shown by the upregulation of Bcl-2, the downregulation of Bax, Cleaved Caspase 3, and Cleaved Caspase 9. CONCLUSION: LYC could ameliorate TiO2 NPs-induced testicular damage via inhibiting oxidative stress and apoptosis, which could be used to alleviate the testicular toxicity associated with TiO2 NPs intake.