Salvianolic Acid B Significantly Suppresses the Migration of Melanoma Cells via Direct Interaction with ß-Actin.

Melanoma is the most aggressive and difficult to treat of all skin cancers. Despite advances in the treatment of melanoma, the prognosis for melanoma patients remains poor, and the recurrence rate remains high. There is substantial evidence that Chinese herbals effectively prevent and treat melanoma. The bioactive ingredient Salvianolic acid B (SAB) found in Salvia miltiorrhiza, a well-known Chinese herbal with various biological functions, exhibits inhibitory activity against various cancers. A375 and mouse B16 cell lines were used to evaluate the main targets and mechanisms of SAB in inhibiting melanoma migration. Online bioinformatics analysis, Western blotting, immunofluorescence, molecular fishing, dot blot, and molecular docking assays were carried out to clarify the potential molecular mechanism. We found that SAB prevents the migration and invasion of melanoma cells by inhibiting the epithelial-mesenchymal transition (EMT) process of melanoma cells. As well as interacting directly with the N-terminal domain of ß-actin, SAB enhanced its compactness and stability, thereby inhibiting the migration of cells. Taken together, SAB could significantly suppress the migration of melanoma cells via direct binding with ß-actin, suggesting that SAB could be a helpful supplement that may enhance chemotherapeutic outcomes and benefit melanoma patients.

Uncovering the effects and molecular mechanism of Astragalus membranaceus (Fisch.) Bunge and its bioactive ingredients formononetin and calycosin against colon cancer: An integrated approach based on network pharmacology analysis coupled with experimental validation and molecular docking.

Colon cancer is a highly malignant cancer with poor prognosis. Astragalus membranaceus (Fisch.) Bunge (Huang Qi in Chinese, HQ), a well-known Chinese herbal medicine and a popular food additive, possesses various biological functions and has been frequently used for clinical treatment of colon cancer. However, the underlying mechanism is not fully understood. Isoflavonoids, including formononetin (FMNT) and calycosin (CS), are the main bioactive ingredients isolated from HQ. Thus, this study aimed to explore the inhibitory effects and mechanism of HQ, FMNT and CS against colon cancer by using network pharmacology coupled with experimental validation and molecular docking. The network pharmacology analysis revealed that FMNT and CS exerted their anticarcinogenic actions against colon cancer by regulating multiple signaling molecules and pathways, including MAPK and PI3K-Akt signaling pathways. The experimental validation data showed that HQ, FMNT and CS significantly suppressed the viability and proliferation, and promoted the apoptosis in colon cancer Caco2 and HT-29 cells. HQ, FMNT and CS also markedly inhibited the migration of Caco2 and HT-29 cells, accompanied by a marked increase in E-cadherin expression, and a notable decrease in N-cadherin and Vimentin expression. In addition, HQ, FMNT and CS strikingly decreased the expression of ERK1/2 phosphorylation (p-ERK1/2) without marked change in total ERK1/2 expression. They also slightly downregulated the p-Akt expression without significant alteration in total Akt expression. Pearson correlation analysis showed a significant positive correlation between the inactivation of ERK1/2 signaling pathway and the HQ, FMNT and CS-induced suppression of colon cancer. The molecular docking results indicated that FMNT and CS had a strong binding affinity for the key molecules of ERK1/2 signaling pathway. Conclusively, HQ, FMNT and CS exerted good therapeutic effects against colon cancer by mainly inhibiting the ERK1/2 signaling pathway, suggesting that HQ, FMNT and CS could be useful supplements that may enhance chemotherapeutic outcomes and benefit colon cancer patients.

Surgical correction of severe congenital ptosis using a modified frontalis muscle advancement technique: A single-arm trial.

PURPOSE: To describe our experience with a modified frontal muscle advancement flap to treat patients with severe congenital ptosis. METHODS: Analysis of the clinical charts of 154 patients who underwent a modified frontal muscle advancement flap. The FM was exposed by a crease incision. The FM flap was created by deep dissection between the orbicularis muscle and orbital septum from the skin crease incision to the supraorbital margin and subcutaneous dissection from the inferior margin of the eyebrow to 0.5 cm above the eyebrow. No vertical incision was made on the FM flap to ensure an intact flap wide enough to cover the entire upper tarsal plate. Contour, symmetry of height, marginal reflex distance (MRD1), and complications were assessed. Mean follow-up was 10 months. RESULTS: The mean patient age was 7.6 ± 5.6 (range, 2-18) years. The mean MRD1 was 3.2 ± 1.3 mm after the operation. All bilateral cases achieved symmetry and optimal lid contour; 17 unilateral cases were under corrected, with a success rate of 89.0%. Complications such as entropion, exposure keratitis, FM paralysis, frontal hypoesthesia, severe haematoma, and entropion were not observed in our series. CONCLUSION: A modified frontal muscle advancement flap produced a high success rate with a clear field of vision, mild trauma, and few complications. This technique is relatively simple and should be considered for correcting severe congenital ptosis.Date of registration: 29-03-2020Trial registration number: ChiCTR2000031364Registration site: http://www.chictr.org/.

Comparative evaluation of conventional and modified frontalis muscle flap advancement techniques in the treatment of severe congenital ptosis: A retrospective cohort study.

PURPOSE: To introduce a modified frontalis muscle (FM) flap for use in FM flap advancement surgery and compare it with the conventional flap for correcting severe congenital ptosis. METHODS: This retrospective cohort study included 200 patients (278 eyes) with severe congenital ptosis treated with FM flap advancement at Tianjin Eye Hospital from April 2018 to October 2019. The patients were divided into two groups: 100 patients (138 eyes) in the conventional group and 100 patients (140 eyes) in the modified group. The success and complication rates were evaluated. RESULTS: The final success rate was 77.5% (107/138) in the conventional group and 90.0% (126/140) in the modified group (p = 0.005). Undercorrection was observed in 31 eyes (22.5%) in the conventional group and 14 eyes (10%) in the modified group (p = 0.005). In the conventional group, angular deformity of the upper eyelid was observed in 29 eyes (21.0%), FM paralysis in 11 (8.0%), frontal hypoesthesia in 10 (7.2%), severe hematoma in 12 (8.7%), and exposure keratitis in 8 (5.8%); these complications were not observed in the modified group (p <0.001, p <0.001, p = 0.004, p <0.001, p = 0.011, respectively). There were no cases of overcorrection, entropion or ectropion in either group. CONCLUSION: Compared with the conventional FM flap, the modified FM flap in this study yielded a higher success rate with a clear field of vision, mild trauma, and few complications. This technique is simple and convenient for correcting severe congenital ptosis.

Near-roadway monitoring of vehicle emissions as a function of mode of operation for light-duty vehicles.

Determination of the effect of vehicle emissions on air quality near roadways is important because vehicles are a major source of air pollution. A near-roadway monitoring program was undertaken in Chicago between August 4 and October 30, 2014, to measure ultrafine particles, carbon dioxide, carbon monoxide, traffic volume and speed, and wind direction and speed. The objective of this study was to develop a method to relate short-term changes in traffic mode of operation to air quality near roadways using data averaged over 5-min intervals to provide a better understanding of the processes controlling air pollution concentrations near roadways. Three different types of data analysis are provided to demonstrate the type of results that can be obtained from a near-roadway sampling program based on 5-min measurements: (1) development of vehicle emission factors (EFs) for ultrafine particles as a function of vehicle mode of operation, (2) comparison of measured and modeled CO2 concentrations, and (3) application of dispersion models to determine concentrations near roadways. EFs for ultrafine particles are developed that are a function of traffic volume and mode of operation (free flow and congestion) for light-duty vehicles (LDVs) under real-world conditions. Two air quality models-CALINE4 (California Line Source Dispersion Model, version 4) and AERMOD (American Meteorological Society/U.S. Environmental Protection Agency Regulatory Model)-are used to predict the ultrafine particulate concentrations near roadways for comparison with measured concentrations. When using CALINE4 to predict air quality levels in the mixing cell, changes in surface roughness and stability class have no effect on the predicted concentrations. However, when using AERMOD to predict air quality in the mixing cell, changes in surface roughness have a significant impact on the predicted concentrations. IMPLICATIONS: The paper provides emission factors (EFs) that are a function of traffic volume and mode of operation (free flow and congestion) for LDVs under real-world conditions. The good agreement between monitoring and modeling results indicates that high-resolution, simultaneous measurements of air quality and meteorological and traffic conditions can be used to determine real-world, fleet-wide vehicle EFs as a function of vehicle mode of operation under actual driving conditions.

Ultrafine-Particle Emission Factors as a Function of Vehicle Mode of Operation for LDVs Based on Near-Roadway Monitoring.

This paper presents ultrafine-particle (UFP) emission factors (EFs) as a function of vehicle mode of operation (free flow and congestion) using (1) concurrent 5 min measurements of UFPs and carbon monoxide (CO) concentration, wind speed and direction, traffic volume and speed near a roadway that is restricted to light-duty vehicles (LDVs) and (2) inverse dispersion model calculations. Short-term measurements are required to characterize the highly variable and rapidly changing UFP concentration generated by vehicles. Under congestion conditions, the UFP vehicle EFs increased from 0.5 × 10(13) to 2 × 10(13) (particles km(-1) vehicle(-1)) when vehicle flow increased from 5500 to 7500 vehicles/h. For free-flow conditions, the EF is constant at 1.5 × 10(13) (particles km(-1) vehicle(-1)). The analysis is based on the assumption that air-quality models adequately describe the dilution process due to both traffic and atmospheric turbulence. The approach used to verify this assumption was to use an emission factor model to determine EFs for CO and then estimate dilution factors using measured CO concentrations. This procedure eliminates the need to rely only on air quality models to generate dilution factors. The EFs are suitable for fleet emissions under real-world traffic conditions.

Orbicularis oculi muscle transposition for repairing involutional lower eyelid entropion.

PURPOSE: To describe a simple technique for involutional entropion correction and to present the findings of a retrospective interventional case series study. METHODS: We studied a consecutive series of 414 patients (609 eyelids). Patients presenting with involutional entropion in the absence of lateral canthal tendon laxity underwent orbicularis oculi muscle (OOM) transposition from pretarsal position to corresponding preseptum without horizontal shortening or resection of the orbicularis muscle. RESULTS: Immediate resolution of entropion and associated ocular symptoms was achieved in 607 eyelids (99.67 %). An early postoperative complication was localized lid swelling that gradually subsided within one week. Over-correction occurred in six cases and resolved with pressure dressing, mostly one or two days post-operation. At final follow-up, a significant improvement in eyelid position was achieved in 579 eyelids (95.07 % ). There was mild recurrence of entropion in 30 eyelids (4.93 %). The mean follow-up was 6.84 months (range, 6-12 months). CONCLUSIONS: Orbicularis oculi muscle transposition is a reasonably successful procedure with a high success rate, and is particularly suitable for patients for whom there exits overriding of the preseptal OOM over the pretarsal OOM.