Increasing the tumour targeting of antitumour drugs through anlotinib-mediated modulation of the extracellular matrix and the RhoA/ROCK signalling pathway.

Anlotinib has strong antiangiogenic effects and leads to vessel normalization. However, the "window period" characteristic in regulating vessel normalization by anlotinib cannot fully explain the long-term survival benefits achieved through combining it with other drugs. In this study, through RNA sequencing (RNA-seq) and label-free quantitative proteomics analysis, we discovered that anlotinib regulated the expression of components of the extracellular matrix (ECM), leading to a significant reduction in ECM stiffness. Our bioinformatic analysis revealed a potential positive relationship between the ECM pathway and gefitinib resistance, poor treatment outcomes for programmed death 1 (PD-1) targeting, and unfavourable prognosis following chemotherapy in lung cancer patients. We administered anlotinib in combination with these antitumour drugs and visualized their distribution using fluorescent labelling in various tumour types. Notably, our results demonstrated that anlotinib prolonged the retention time and distribution of antitumour drugs at the tumour site. Moreover, the combination therapy induced notable loosening of the tumour tissue structure. This reduction was associated with decreased interstitial fluid pressure and tumour solid pressure. Additionally, we observed that anlotinib effectively suppressed the Ras homologue family member A (RhoA)/Rho-associated protein kinase (ROCK) signalling pathway. These findings suggest that, in addition to its antiangiogenic and vessel normalization effects, anlotinib can increase the distribution and retention of antitumour drugs in tumours by modulating ECM expression and physical properties through the RhoA/ROCK signalling pathway. These valuable insights contribute to the development of combination therapies aimed at improving tumour targeting in cancer treatment.

Identification and analysis of significant genes in nonalcoholic steatohepatitis-hepatocellular carcinoma transformation: Bioinformatics analysis and machine learning approach.

PURPOSE: Nonalcoholic steatohepatitis (NASH) has been an increasingly significant contributor to hepatocellular carcinoma (HCC). Understanding the progression from NASH to HCC is critical to early diagnosis and elucidating the underlying mechanisms. RESULTS: 5 significant prognostic genes related to NASH-HCC transformation were identified through algorithm selection, which were ME1, TP53I3, SOCS2, GADD45G and CYP7A1. A diagnostic model for NASH prediction was established (AUC=0.988). TP53I3 and SOCS2 were selected as potential critical genes in the progression of NASH-HCC by external dataset validation and in vitro experiments on NASH and HCC cell lines. Immune infiltration analysis illustrated the correlation between 5 significant prognostic genes and immune cells. Single-cell analysis identified hepatocytes related to NASH-HCC transformation markers, revealing their promoting role in the transformation from NASH to HCC. CONCLUSION: With bulk-seq analysis and single-cell analysis, 5 significant prognostic genes related to NASH-HCC transformation were identified and validated at both dataset and in vitro experiment level. Among them, TP53I3 and SOCS2 might be potential critical genes in NASH-HCC progression. Single-cell analysis identified and revealed the critical role that NASH-HCC related hepatocytes play in NASH-HCC tansformation. Our research may introduce a new perspective to the diagnosis, treatment of NASH-related HCC.

Exploration of SERPINA family functions and prognostic value in breast cancer based on transcriptome and in vitro analysis.

Breast cancer poses a significant risk to women worldwide, yet specific role of SERPINA gene family in breast cancer remains unclarified. Data were collected from online databases. SERPINA family gene expression was presented, and prognosis value was evaluated. Multi-omics methods were employed to explore the SERPINA-related biological processes, followed by comprehensive analyses of their roles in breast cancer. Single-cell data were analyzed to characterize the SERPINA family gene expression in different cell clusters. We selected SERPINA5 as the target gene. Via pan-cancer analysis, SERPINA5 was also investigated in various cancers. The experimental validation was conducted in MDA-MB-231 cell line eventually. SERPINA family showed differential expression in breast cancer, which were mainly expressed in myeloid cells, epithelial cells, and dendritic cells. SERPINA5 expression was upregulated in breast cancer, which was associated with a better prognosis. Immune infiltration illustrated the positive correlativity between SERPINA5 intensity and eosinophilic recruitment. Pan-cancer analysis indicated the function of SERPINA5 as a potential biomarker in other cancers. Finally, experimental validation demonstrated that SERPINA5 contributes to lower invasion and metastatic potential of breast cancer cells. With bioinformatics analysis, the significant role SERPINA family genes functioned in breast cancer was comprehensively explored, with SERPINA5 emerging as a key gene in suppressing breast cancer progression.

Efficacy of augmented-dosed surgery versus botulinum toxin A injection for acute acquired concomitant esotropia: a 2-year follow-up.

BACKGROUND/AIMS: This study aims to evaluate the clinical efficacy of botulinum toxin type A (BTXA) injection and augmented-dosed surgery in the treatment of acute acquired concomitant esotropia (AACE), and explore potential risk factors associated with recurrence. METHODS: A total of 104 patients diagnosed with AACE between October 2020 and January 2021 were included and voluntarily chose to undergo augmented surgery or BTXA injection. The follow-up assessments ended in November 2022. Multivariable linear regression analysis was used to identify potential factors that influence the dose-response of bilateral medial rectus recession (MRrec). Kaplan-Meier survival analyses and Cox proportional hazards models were performed to evaluate rate and risk factors for AACE relapse. RESULTS: A total of 31 AACE patients chose augmented-dosed esotropia surgery, and 73 chose BTXA treatment. During the 2-year follow-up, the surgical group achieved more stable postoperative results with no recurrence of diplopia, while only 68.68% (95% CI 55.31% to 78.79%) patients achieved orthophoria in the BTXA group. For patients undergoing BTXA treatment, hours of near work per day were demonstrated to be a significant risk factor for AACE relapse (HR 1.29, 95% CI 1.00 to 1.67). The dose-response of augmented-dosed bilateral MRrec was positively correlated with preoperative deviation angle (R2=0.833; ß=0.043, 95% CI 0.031 to 0.055; p<0.001). CONCLUSION: Our findings provided quantitative evidence that augmented-dosed surgery would achieve more stable and favourable surgical outcomes for AACE patients compared with BTXA injection. However, BTXA treatment is still proposed for patients with small deviation angles due to its advantages of reduced trauma, operational simplicity, low cost and quick recovery.

Synthesis of Castor Oil-Based Quaternary Ammonium Salt and Modification of Attapulgite for Treating Industrial Wastewaters.

In order to develop multifunctional quaternary ammonium salts and explore their advantages as modifiers for wastewater treatment, castor oil-based quaternary ammonium salts were synthesised and subsequently used as modifiers for attapulgite treatment. The structures of untreated and treated attapulgite were compared by Fourier transform infrared spectra and X-ray diffraction. The mechanism of modification was speculated. Various factors such as the amount of modified attapulgite, temperature and pH were also investigated in the batch experiments on the removal rates of acetone and phenol from wastewaters. The synthesis conditions were set as follows: the reaction temperature was 80 °C, the reaction time was 8 h, the molar ratio of castor oil to N,N-dimethyl-1,3-propanediamine was 1:5, the catalyst was 6% NaOH and the product yield was about 64.72%. The grafting rate of the castor oil-based quaternary ammonium salt was about 99.6% when the amount of modifier was 0.69 g per 5 g of attapulgite, the ultrasound treatment time was 11 min and the pH was 5. The quaternary ammonium salt was only associated with the surface of attapulgite and did not change the rod-like crystal structure of the silicate. The modified attapulgite is much more fibrous and exhibits a good distribution of crystal bundles. The removal rates were found to be less favourable under strongly acidic and strongly alkaline conditions. Under suitable conditions, for 50 mL industrial wastewaters (phenol: 100-160 mg/L; acetone: 680-800 mg/L), the amount of modified attapulgite was 1 g, the temperature was 80 °C and the pH was 7, and the maximum removal rates of acetone and phenol after 80 min reached about 65.71% and 78.72%, respectively, which were higher than those of ATP.

Research Progress Concerning a Novel Intraocular Lens for the Prevention of Posterior Capsular Opacification.

Posterior capsular opacification (PCO) is the most common complication resulting from cataract surgery and limits the long-term postoperative visual outcome. Using Nd:YAG laser-assisted posterior capsulotomy for the clinical treatment of symptomatic PCO increases the risks of complications, such as glaucoma, retinal diseases, uveitis, and intraocular lens (IOL) pitting. Therefore, finding how to prevent PCO development is the subject of active investigations. As a replacement organ, the IOL is implanted into the lens capsule after cataract surgery, but it is also associated with the occurrence of PCO. Using IOL as a medium for PCO prophylaxis is a more facile and efficient method that has demonstrated various clinical application prospects. Thus, scientists have conducted a lot of research on new intraocular lens fabrication methods, such as optimizing IOL materials and design, and IOL surface modification (including plasma/ultraviolet/ozone treatment, chemical grafting, drug loading, coating modification, and layer-by-layer self-assembly methods). This paper summarizes the research progress for different types of intraocular lenses prepared by different surface modifications, including anti-biofouling IOLs, enhanced-adhesion IOLs, micro-patterned IOLs, photothermal IOLs, photodynamic IOLs, and drug-loading IOLs. These modified intraocular lenses inhibit PCO development by reducing the residual intraoperative lens epithelial cells or by regulating the cellular behavior of lens epithelial cells. In the future, more works are needed to improve the biosecurity and therapeutic efficacy of these modified IOLs.

Remimazolam reduces sepsis-associated acute liver injury by activation of peripheral benzodiazepine receptors and p38 inhibition of macrophages.

BACKGROUND: Remimazolam is a novel ester-type benzodiazepine with ultrafast onset of sedation effect and fast recovery of consciousness. It has potential advantages in the sedation of sepsis-associated acute liver injury (SALI) patients. However, the effect and mechanism of remimazo lam on inflammation in the liver have not yet been elucidated. This study investigated the anti-inflammatory effects and mechanisms of remimazolam on SALI both in vivo and in vitro. METHODS: Lipopolysaccharide (LPS) plus galactosamine treated rat model and LPS-challenged RAW264.7 cells model were constructed to simulate SALI. Next, the models were used to explore the efficacy of remimazolam treatment on SALI. Benzodiazepine receptor inhibitor, PK11195, was also employed. Hepatic injury was assessed by quantifying levels of transaminases, examining liver pathology, and calculating the number of inflammatory cells in the liver. Inflammatory response was evaluated by determining levels of pro-inflammatory cytokines and chemokines in blood, as well as p38 phosphorylation (p-p38) in the liver. RESULTS: SALIrat models showed significant liver damage as manifested by increased levels of transaminases, proinflammatory cytokines, chemokines, and p-38. Remimazolam treatment reduced the liver injury and pathological changes, suppressed pro-inflammatory reactions, and elevated p-p38. The protective effect of remimazolam on liver injury was significantly blocked by PK11195. In LPS-stimulated RAW264.7 cells, it was found that treatment with remimazolam reduced the inflammatory response in LPS-treated cells in a time-dependent manner and decreased the level of p-p38. These results suggest that PK11195 can block remimazolam-induced inhibition of proinflammatory cytokine release and p-38 phosphorylation. CONCLUSIONS: This study shows that remimazolam can attenuate inflammatory response in SALI, which may be associated with activation of peripheral benzodiazepine receptors and inhibition of p38 phosphorylation in macrophages.

Exogenous inoculation of endophytic bacterium Bacillus cereus suppresses clubroot (Plasmodiophora brassicae) occurrence in pak choi (Brassica campestris sp. chinensis L.).

MAIN CONCLUSION: The presence of Bacillus cereus plays a key role in clubroot suppression and improves plant biomass in pak choi. B. cereus is reported for the first time as a novel biocontrol agent against clubroot. Plasmodiophora brassicae Woronin causes a devastating infectious disease known as clubroot that is damaging to cruciferous vegetables. This study aimed to isolate beneficial bacteria from the rhizosphere soil of pak choi (Brassica campestris sp. chinensis) and to evaluate the ability of the isolate to reduce the severity of clubroot. Strains obtained from the rhizosphere of symptomless pak choi were first selected on the basis of their germination inhibition rate and effects on the viability of P. brassicae resting spores. Eight bacterial isolates had inhibitory effects against the resting spores of clubroot causing pathogen. However, MZ-12 showed the highest inhibitory effect at 73.4%. Inoculation with MZ-12 enhanced the plant biomass relative to plants grown without MZ-12 as well as P. brassicae infected plants. Furthermore, enhanced antioxidant enzymatic activities were observed in clubroot-infected plants during bacterial association. Co-inoculation of the plant with both P. brassicae and MZ-12 resulted in a 64% reduction of gall formation in comparison to plants inoculated with P. brassicae only. Three applications of MZ-12 to plants infected with P. brassicae at 7, 14 and 21 days after seeding (DAS) were more effective than one application and repressed root hair infection. According to 16S rDNA sequence analysis, strain MZ-12 was identified as had a 100% sequence similarity with type strain Bacillus cereus. The findings of the present study will facilitate further investigation into biological mechanisms of cruciferous clubroot control.

Impact of the Incorporation of Nano-Sized Cellulose Formate on the End Quality of Polylactic Acid Composite Film.

Polylactic acid (PLA) films with good sustainable and biodegradable properties have been increasingly explored recently, while the poor mechanical property of PLA limits its further application. Herein, three kinds of nano-sized cellulose formate (NCF: cellulose nanofibril (CNF), cellulose nanocrystal (CNC), and regenerated cellulose formate (CF)) with different properties were fabricated via a one-step formic acid (FA) hydrolysis of tobacco stalk, and the influence of the properties of NCF with different morphologies, crystallinity index (CrI), and degree of substitution (DS) on the end quality of PLA composite film was systematically compared. Results showed that the PLA/CNC film showed the highest increase (106%) of tensile strength compared to the CNF- and CF-based films, which was induced by the rod-like CNC with higher CrI. PLA/CF film showed the largest increase (50%) of elongation at the break and more even surface, which was due to the stronger interfacial interaction between PLA and the CF with higher DS. Moreover, the degradation property of PLA/CNF film was better than that of other composite films. This fundamental study was very beneficial for the development of high-quality, sustainable packaging as an alternative to petroleum-based products.

Prognostic value of tumor-infiltrating lymphocytes in esophageal cancer: an updated meta-analysis of 30 studies with 5,122 patients.

BACKGROUND: The prognostic role of tumor-infiltrating lymphocytes (TILs) in esophageal cancer (EC) patients is controversial; therefore, we performed a meta-analysis to obtain a consensus. METHODS: The PubMed, PubMed Central, Embase, Cochrane Library, and Web of Science databases were searched. The pooled hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated using fixed effect or random effect models depending on the heterogeneity. RESULTS: A total of 30 articles comprising 5,122 patients were included in this meta-analysis. High levels of generalized TIL infiltration were associated with better overall survival (OS) (HR =0.67, 95% CI: 0.47-0.95, P=0.02) in EC patients. High CD8+ T-cell infiltration and high CD4+ T-cell infiltration were associated with better OS (HR =0.68, 95% CI: 0.60-0.78, P<0.001; HR =0.70, 95% CI: 0.57-0.85, P<0.001, respectively). However, the pooled results showed that neither CD3+ nor FOXP3+ T-cell infiltration were associated with patient survival (P>0.05). Moreover, for esophageal squamous cell carcinoma (ESCC), high CD8+ T lymphocyte infiltration in the TN (Tumor nest) or TS (Tumor stroma) significantly predicted better OS (pooled HR =0.70, 95% CI: 0.57-0.85; P=0.001; pooled HR =0.77, 95% CI: 0.65-0.91; P=0.003). CONCLUSIONS: High levels of generalized TILs, high CD8+ T-cell infiltration and high CD4+ T-cell infiltration have the potential to serve as prognostic markers in EC patients. Moreover, high CD8+ TIL in TNs or TS can predict better OS in ESCC patients.

Supportive role of the Na+ transporter CmHKT1;1 from Cucumis melo in transgenic Arabidopsis salt tolerance through improved K+/Na+ balance.

KEY MESSAGE: CmHKT1;1 selectively exports Na+ from plant cells. Upon NaCl stress, its expression increased in a salt-tolerant melon cultivar. Overexpression of CmHKT1;1 increased transgenic Arabidopsis salt tolerance through improved K+/Na+ balance. High-affinity K+ transporters (HKTs) are thought to be involved in reducing Na+ in plant shoots under salt stress and modulating salt tolerance, but their function in a moderately salt-tolerant species of melon (Cucumis melo L.) remains unclear. In this study, a Na+ transporter gene, CmHKT1;1 (GenBank accession number: MK986658), was isolated from melons based on genome data. The transcript of CmHKT1;1 was relatively more abundant in roots than in stems or leaves from melon seedlings. The tobacco transient expression system showed that CmHKT1;1 was plasma-membrane localized. Upon salt stress, CmHKT1;1 expression was more strongly upregulated in a salt-tolerant melon cultivar, 'Bingxuecui' (BXC) compared with a salt-sensitive cultivar, 'Yulu' (YL). Electrophysiological evidence demonstrated that CmHKT1;1 only transported Na+, rather than K+, when expressed in Xenopus laevis oocytes. Overexpression of CmHKT1;1 increased salt sensitivity in Saccharomyces cerevisiae and salt tolerance in Arabidopsis thaliana. Under NaCl treatments, transgenic Arabidopsis plants accumulated significantly lower concentrations of Na+ in shoots than wild type plants and showed a better K+/Na+ balance, leading to better Fv/Fm, root length, biomass, and enhanced plant growth. The CmHKT1;1 gene may serve as a useful candidate for improving crop salt tolerance.

Neuroprotection Effect of Astragaloside IV from 2-DG-Induced Endoplasmic Reticulum Stress.

OBJECTIVE: Astragaloside IV shows neuroprotective activity, but its mechanism remains unclear. To investigate whether astragaloside IV protects from endoplasmic reticulum stress (ERS), we focus on the regulation of glycogen synthase kinase-3ß (GSK-3ß) and mitochondrial permeability transition pore (mPTP) by astragaloside IV in neuronal cell PC12. METHODS AND RESULTS: PC12 cells treated with different concentrations of ERS inductor 2-deoxyglucose (2-DG) (25-500 µM) showed a significant increase of glucose-regulated protein 78 (GRP 78) and GRP 94 expressions and a decrease of tetramethylrhodamine ethyl ester (TMRE) fluorescence intensity and mitochondrial membrane potential (∆Ψm), with the peak effect seen at 50 µM, indicating that 2-DG induces ERS and the mPTP opening. Similarly, 50 µM of astragaloside IV increased the GSK-3ß phosphorylation at Ser9 most significantly. Next, we examined the neuroprotection of astragaloside IV by dividing the PC12 cells into control group, 2-DG treatment group, astragaloside IV plus 2-DG treatment group, and astragaloside IV only group. PC12 cells treated with 50 µM 2-DG for different time courses (0-36 hr) showed a significant increase of Cleaved-Caspase-3 with the peak at 6 hr. 2-DG significantly induced cell apoptosis and increased the green fluorescence intensity of Annexin V-FITC, and these effects were reversed by astragaloside IV. Such a result indicates that astragaloside IV protected neural cell survival from ERS. 2-DG treatment significantly increased the expressions of inositol-requiring ER-to-nucleus signal kinase 1 (IRE1), phosphor-protein kinase R-like ER kinase (p-PERK), but not affect the transcription factor 6 (ATF6) expression. 2-DG treatment significantly decreased the phosphorylation of GSK-3ß and significantly reduced the TMRE fluorescence intensity and ∆Ψm, following mPTP open. Astragaloside IV significantly inhibited the above effects caused by 2-DG, except the upregulation of ATF6 protein. Taken together, astragaloside IV significantly inhibited the ERS caused by 2-DG. CONCLUSION: Our data suggested that astragaloside IV protects PC12 cells from ERS by inactivation of GSK-3ß and preventing the mPTP opening. The GRP 78, GRP 94, IRE1, and PERK signaling pathways but not ATF6 are responsible for GSK-3ß inactivation and neuroprotection by astragaloside IV.

Application of gluteus maximus fasciocutaneous V-Y advancement flap combined with resection in sacrococcygeal pressure ulcers: A CONSORT-compliant article.

BACKGROUND: Traditional gluteus maximus myocutaneous flaps have generally been used to fill tissue defects after resection of sacrococcygeal pressure ulcers. However, postoperative complications were gradually revealed as increasing operations were performed. This study aimed to introduce the innovative application of gluteus maximus fasciocutaneous V-Y advancement flaps for repairing tissue defects and to comparatively analyze the differences between the innovative and traditional flaps. METHODS: A total of 32 cases were included in this study. All the PU lesions were removed by resection. Sixteen cases used the gluteus maximus myocutaneous flaps, and the remaining 16 cases used gluteus maximus fasciocutaneous V-Y advancement flaps to fill the tissue defects after surgery. Comparative analysis between the gluteus maximus myocutaneous flaps and gluteus maximus fasciocutaneous V-Y advancement flaps was used to evaluate the 2 flaps based on the mean operating time, postoperative infection, paresthesia, appearance of flaps, and recurrence. RESULTS: The gluteus maximus fasciocutaneous V-Y advancement flaps required a reduced operating time and a more simple operation compared with the gluteus maximus myocutaneous flaps. Although the infectious risk of the gluteus maximus fasciocutaneous V-Y advancement flaps was reduced compared with the gluteus maximus myocutaneous flaps, the gluteus maximus myocutaneous flaps have a better appearance compared with the gluteus maximus fasciocutaneous V-Y advancement flaps. Most importantly, no flap necrosis was noted, and the recurrence rate during follow-up was reduced in cases using the gluteus maximus fasciocutaneous V-Y advancement flaps. CONCLUSION: The combined application of gluteus maximus fasciocutaneous V-Y advancement flaps with surgical resection can reduce the postoperative complications and aid in the treatment of sacrococcygeal pressure ulcers.

Roles of Endoplasmic Reticulum Stress in NECA-Induced Cardioprotection against Ischemia/Reperfusion Injury.

OBJECTIVE: This study aimed to investigate whether the nonselective A2 adenosine receptor agonist NECA induces cardioprotection against myocardial ischemia/reperfusion (I/R) injury via glycogen synthase kinase 3ß (GSK-3ß) and the mitochondrial permeability transition pore (mPTP) through inhibition of endoplasmic reticulum stress (ERS). METHODS AND RESULTS: H9c2 cells were exposed to H2O2 for 20 minutes. NECA significantly prevented H2O2-induced TMRE fluorescence reduction, indicating that NECA inhibited the mPTP opening. NECA blocked H2O2-induced GSK-3ß phosphorylation and GRP94 expression. NECA increased GSK-3ß phosphorylation and decreased GRP94 expression, which were prevented by both ERS inductor 2-DG and PKG inhibitor KT5823, suggesting that NECA may induce cardioprotection through GSK-3ß and cGMP/PKG via ERS. In isolated rat hearts, both NECA and the ERS inhibitor TUDCA decreased myocardial infarction, increased GSK-3ß phosphorylation, and reversed GRP94 expression at reperfusion, suggesting that NECA protected the heart by inhibiting GSK-3ß and ERS. Transmission electron microscopy showed that NECA and TUDCA reduced mitochondrial swelling and endoplasmic reticulum expansion, further supporting that NECA protected the heart by preventing the mPTP opening and ERS. CONCLUSION: These data suggest that NECA prevents the mPTP opening through inactivation of GSK-3ß via ERS inhibition. The cGMP/PKG signaling pathway is responsible for GSK-3ß inactivation by NECA.

A comparable study of clinical and optical outcomes after 1.8, 2.0 mm microcoaxial and 3.0 mm coaxial cataract surgery.

AIM: To evaluate the clinical and optical outcomes after clear corneal incision cataract surgery (CICS) with three different incision sizes (1.8, 2.0 and 3.0 mm). METHODS: Eyes of 150 patients with age-related cataract scheduled for coaxial cataract surgery were randomized to three groups: 1.8, 2.0, or 3.0 mm CICS. Intraoperative data and postoperative outcomes including surgically induced astigmatism (SIA), the corneal incision thickness, wavefront aberrations and modulation transfer function (MTF) of cornea were obtained. RESULTS: There were no significant differences among the three groups in demographic characteristics and intraoperative outcome. The 1.8 and 2.0 mm microincisions showed more satisfactory clinical outcomes than the 3.0 mm incision. The 1.8 mm incision showed significantly less SIA than the 2.0 mm incision until postoperative 1mo (P<0.05), but the difference was only 0.14-0.18 D. Combined with less increased incision thickness only at postoperative 1d (P=0.013), the 1.8 mm incision presented better uncorrected distance visual acuity (UCDVA) than the 2.0 mm incision only at 1d postoperatively (P=0.008). For higher-order aberrations and other Zernike coefficients, there were no significant differences between the 1.8 mm group and 2.0 mm group (P>0.05). CONCLUSION: Converting from 3.0 mm CICS to 1.8 or 2.0 mm CICS result in better clinical and optical outcomes. However, when incision is 1.8 mm, the benefits from further reduction in size compared with 2.0 mm are limited. The necessity to reduce the incision size is to be deliberated.

Study of oxidative stress in human lens epithelial cells exposed to 1.8 GHz radiofrequency fields.

OBJECTIVES: The aims of the present study were to determine oxidative stress and to explore possible reasons of reactive oxygen species (ROS) increase in human lens epithelial (HLE) B3 cells exposed to low intensity 1.8 GHz radiofrequency fields (RF). METHODS: The HLE B3 cells were divided into RF exposure and RF sham-exposure groups. The RF exposure intensity was at specific absorption rate (SAR) of 2, 3, or 4 W/kg. The ROS levels were measured by a fluorescent probe 2'7'-dichlorofluorescin diacetate (DCFH-DA) assay in the HLE B3 cells exposed to 1.8 GHz RF for 0.5, 1, and 1.5 h. Lipid peroxidation and cellular viability were detected by an MDA test and Cell Counting Kit-8 (CCK-8) assays, respectively, in the HLE B3 cells exposed to 1.8 GHz RF for 6, 12, and 24 h, respectively. The mRNA expression of SOD1, SOD2, CAT, and GPx1 genes and the expression of SOD1, SOD2, CAT, and GPx1 proteins was measured by qRT-PCR and Western blot assays in the HLE B3 cells exposed to 1.8 GHz RF for 1 h. RESULTS: The ROS and MDA levels significantly increased (P<0.05) in the RF exposure group and that the cellular viability, mRNA expression of four genes, and expression of four proteins significantly decreased (P<0.05) compared with the RF sham-exposure group. CONCLUSIONS: Oxidative stress is present in HLE B3 cells exposed to 1.8 GHz low-intensity RF and that the increased production of ROS may be related to down-regulation of four antioxidant enzyme genes induced by RF exposure.

Astragaloside IV inhibits oxidative stress-induced mitochondrial permeability transition pore opening by inactivating GSK-3ß via nitric oxide in H9c2 cardiac cells.

OBJECTIVE: This study aimed to investigate whether astragaloside IV modulates the mitochondrial permeability transition pore (mPTP) opening through glycogen synthase kinase 3ß (GSK-3ß) in H9c2 cells. METHODS: H9c2 cells were exposed to astragaloside IV for 20 min. GSK-3ß (Ser(9)), Akt (Ser(473)), and VASP (Ser(239)) activities were determined with western blot. The mPTP opening was evaluated by measuring mitochondrial membrane potential (ΔΨ(m)). Nitric oxide (NO) generation was measured by 4-amino-5-methylamino-2', 7'-difluorofluorescein (DAF-FM) diacetate. Fluorescence images were obtained with confocal microscopy. RESULTS: Astragaloside IV significantly enhanced GSK-3ß phosphorylation and prevented H(2)O(2)-induced loss of ΔΨ(m). These effects of astragaloside IV were reversed by the phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002, the NO sensitive guanylyl cyclase selective inhibitor ODQ, and the PKG inhibitor KT5823. Astragaloside IV activated Akt and PKG. Astragaloside IV was also shown to increase NO production, an effect that was reversed by L-NAME and LY294002. Astragaloside IV applied at reperfusion reduced cell death caused by simulated ischemia/reperfusion, indicating that astragaloside IV can prevent reperfusion injury. CONCLUSIONS: These data suggest that astragaloside IV prevents the mPTP opening and reperfusion injury by inactivating GSK-3ß through the NO/cGMP/PKG signaling pathway. NOS is responsible for NO generation and is activated by the PI3K/Akt pathway.

Extranuclear estrogen receptors mediate the neuroprotective effects of estrogen in the rat hippocampus.

BACKGROUND: 17beta-estradiol (E2) has been implicated to exert neuroprotective effects in the brain following cerebral ischemia. Classically, E2 is thought to exert its effects via genomic signaling mediated by interaction with nuclear estrogen receptors. However, the role and contribution of extranuclear estrogen receptors (ER) is unclear and was the subject of the current study. METHODOLOGY/PRINCIPAL FINDINGS: To accomplish this goal, we employed two E2 conjugates (E2 dendrimer, EDC, and E2-BSA) that can interact with extranuclear ER and exert rapid nongenomic signaling, but lack the ability to interact with nuclear ER due to their inability to enter the nucleus. EDC or E2-BSA (10 microM) was injected icv 60 min prior to global cerebral ischemia (GCI). FITC-tagged EDC or E2-BSA revealed high uptake in the hippocampal CA1 region after icv injection, with a membrane (extranuclear) localization pattern in cells. Both EDC and E2-BSA exerted robust neuroprotection in the CA1 against GCI, and the effect was blocked by the ER antagonist, ICI182,780. EDC and E2-BSA both rapidly enhanced activation of the prosurvival kinases, ERK and Akt, while attenuating activation of the proapoptotic kinase, JNK following GCI, effects that were blocked by ICI182,780. Administration of an MEK or PI3K inhibitor blocked the neuroprotective effects of EDC and E2-BSA. Further studies showed that EDC increased p-CREB and BDNF in the CA1 region in an ERK- and Akt-dependent manner, and that cognitive outcome after GCI was preserved by EDC in an ER-dependent manner. CONCLUSIONS/SIGNIFICANCE: In conclusion, the current study demonstrates that activation of extranuclear ER results in induction of ERK-Akt-CREB-BDNF signaling in the hippocampal CA1 region, which significantly reduces ischemic neuronal injury and preserves cognitive function following GCI. The study adds to a growing literature that suggests that extranuclear ER can have important actions in the brain.

Uveal and capsular biocompatibility of an intraocular lens with a hydrophilic anterior surface and a hydrophobic posterior surface.

PURPOSE: To evaluate the uveal and capsular biocompatibility of intraocular lenses (IOLs) with a hydrophilic anterior surface and a hydrophobic posterior surface in a rabbit model. SETTING: Eye Center, Affiliated Second Hospital, College of Medicine, Zhejiang University, Hangzhou, China. METHODS: Modified silicone IOLs were produced by grafting 2-methacryloyloxyethyl phosphorylcholine (MPC) onto the anterior IOL surface using a plasma technique. A contact-angle test characterized the hydrophilicity of the IOL surface; physical and optical properties were determined by State Food and Drug Administration (SFDA) standards. Rabbits had phacomulsification and implantation a modified silicone IOL, a control silicone IOL, or a hydrogel IOL. Postoperative inflammation was assessed by aqueous flare measurement, and PCO was evaluated by software analysis. Three months after surgery, attached cells on extracted IOLs were evaluated by light microscopy; PCO was evaluated by Miyake-Apple technique. Histologic sections of globes were used to assess lens epithelial cells (LECs) and extracellular matrix in the capsular bag. RESULTS: Contact angle data showed the MPC-modified IOL had a hydrophilic anterior surface and hydrophobic posterior surface. The properties of the modified IOLs met SFDA standards. There was no statistical difference in aqueous flare between the IOL groups at any time. The modified and control IOLs had less PCO than the hydrogel IOLs (P<.05). There were fewer cells on modified IOLs than on silicone IOLs (P<.05). The LECs and cortical remnants on modified IOLs had a rapid, fibroblastic appearance at the optic periphery; the center was clear. CONCLUSIONS: Results suggest that the MPC-modified IOL has excellent uveal and capsule biocompatibility from hydrophilic anterior surface and hydrophobic posterior surface properties, respectively.

Protective effect of magnolol against hydrogen peroxide-induced oxidative stress in human lens epithelial cells.

Oxidative stress plays a significant role in the progression of cataract. We aimed to investigate the protective effect of magnolol, a compound extracted from the Chinese herb Magnolia officinalis, against oxidative stress in human lens epithelial (HLE) cells as well as the possible molecular mechanism involved. In this study, magnolol was observed to protect against H2O2-induced cytotoxicity in HLE B-3 cells. Magnolol inhibited the generation of reactive oxygen species (ROS), loss of mitochondrial membrane potential (Delta psi m) and release of cytochrome c from mitochondria caused by H2O2 into cytosol in HLE B-3 cells. Magnolol also inhibited H2O2-induced expressions of caspase-9 and caspase-3 and reduction of Bcl-2/Bax ratio. Moreover, magnolol attenuated the deactivation of ERK/MAPK (extracellular signal-regulated kinase/mitogen activated protein kinase) and the enhanced activation of p38, JNK (c-Jun N-terminal kinase) induced by H2O2. Magnolol could be useful in protecting against oxidative stress in HLE cells, suggesting a potential protective effect against cataractogenesis effect against cataractogenesis.