Self-assembled active actomyosin gels spontaneously curve and wrinkle similar to biological cells and tissues.

Living systems adopt a diversity of curved and highly dynamic shapes. These diverse morphologies appear on many length scales, from cells to tissues and organismal scales. The common driving force for these dynamic shape changes are contractile stresses generated by myosin motors in the cell cytoskeleton, that converts chemical energy into mechanical work. A good understanding of how contractile stresses in the cytoskeleton arise into different three-dimensional (3D) shapes and what are the shape selection rules that determine their final configurations is still lacking. To obtain insight into the relevant physical mechanisms, we recreate the actomyosin cytoskeleton in vitro, with precisely controlled composition and initial geometry. A set of actomyosin gel discs, intrinsically identical but of variable initial geometry, dynamically self-organize into a family of 3D shapes, such as domes and wrinkled shapes, without the need for specific preprogramming or additional regulation. Shape deformation is driven by the spontaneous emergence of stress gradients driven by myosin and is encoded in the initial disc radius to thickness aspect ratio, which may indicate shaping scalability. Our results suggest that while the dynamical pathways may depend on the detailed interactions between the different microscopic components within the gel, the final selected shapes obey the general theory of elastic deformations of thin sheets. Altogether, our results emphasize the importance for the emergence of active stress gradients for buckling-driven shape deformations and provide insights on the mechanically induced spontaneous shape transitions in contractile active matter, revealing potential shared mechanisms with living systems across scales.

Unlocking the potential of higher-molecular-weight 5-HT7R ligands: Synthesis, affinity, and ADMET examination.

An increasing number of drugs introduced to the market and numerous repositories of compounds with confirmed activity have posed the need to revalidate the state-of-the-art rules that determine the ranges of properties the compounds should possess to become future drugs. In this study, we designed a series of two chemotypes of aryl-piperazine hydantoin ligands of 5-HT7R, an attractive target in search for innovative CNS drugs, with higher molecular weight (close to or over 500). Consequently, 14 new compounds were synthesised and screened for their receptor activity accompanied by extensive docking studies to evaluate the observed structure-activity/properties relationships. The ADMET characterisation in terms of the biological membrane permeability, metabolic stability, hepatotoxicity, cardiotoxicity, and protein plasma binding of the obtained compounds was carried out in vitro. The outcome of these studies constituted the basis for the comprehensive challenge of computational tools for ADMET properties prediction. All the compounds possessed high affinity to the 5-HT7R (Ki below 250 nM for all analysed structures) with good selectivity over 5-HT6R and varying affinity towards 5-HT2AR, 5-HT1AR and D2R. For the best compounds of this study, the expression profile of genes associated with neurodegeneration, anti-oxidant response and anti-inflammatory function was determined, and the survival of the cells (SH-SY5Y as an in vitro model of Alzheimer's disease) was evaluated. One 5-HT7R agent (32) was characterised by a very promising ADMET profile, i.e. good membrane permeability, low hepatotoxicity and cardiotoxicity, and high metabolic stability with the simultaneous high rate of plasma protein binding and high selectivity over other GPCRs considered, together with satisfying gene expression profile modulations and neural cell survival. Such encouraging properties make it a good candidate for further testing and optimisation as a potential agent in the treatment of CNS-related disorders.

Analysis of key targets for 5-hydroxymethyl-2-furfural-induced lung cancer based on network toxicology, network informatics, and in vitro experiments.

5-hydroxymethyl-2-furfural (5-HMF) is a by-product of Maillard reaction and widely exists in food and environment, which may lead to lung cancer. However, the relevant mechanism is unknown. This study aims to predict the key targets of 5-HMF-induced lung cancer through network toxicology, analyze the relationship between the key targets and lung cancer through network informatics, and further validate them through in vitro experiments. By using ChEMBL, STITCH, GeneCards, and OMIM databases, 51 toxic targets were identified. GO and KEGG enrichment analyses indicated a strong correlation between toxic targets and lung cancer. Through protein-protein interaction (PPI) analysis, MAPK3, MAPK1, and SRC were identified as key targets implicated in 5-HMF-induced lung cancer. The HPA database showed high expression of these three key targets in lung cancer tissues. Kaplan-Meier database demonstrated that the higher expression of these key targets in lung cancer patients was associated with a poorer prognosis. The TIMER database revealed that the high expression of these key targets had a significant impact on the level of immune cell infiltration in lung cancer, particularly impacting CD4+ T cells and macrophages. Finaly, in In vitro experiments demonstrated that prolonged exposure to 5-HMF induced malignant transformation of BEAS-2B cells and the upregulation of key targets. The findings suggest that 5-HMF is a contributing factor in the development of lung cancer, with MAPK3, MAPK1, and SRC potentially playing crucial roles in this process.

Integrating In Silico and In Vitro Approaches to Identify Natural Peptides with Selective Cytotoxicity against Cancer Cells.

Anticancer peptides (ACPs) are bioactive compounds known for their selective cytotoxicity against tumor cells via various mechanisms. Recent studies have demonstrated that in silico machine learning methods are effective in predicting peptides with anticancer activity. In this study, we collected and analyzed over a thousand experimentally verified ACPs, specifically targeting peptides derived from natural sources. We developed a precise prediction model based on their sequence and structural features, and the model's evaluation results suggest its strong predictive ability for anticancer activity. To enhance reliability, we integrated the results of this model with those from other available methods. In total, we identified 176 potential ACPs, some of which were synthesized and further evaluated using the MTT colorimetric assay. All of these putative ACPs exhibited significant anticancer effects and selective cytotoxicity against specific tumor cells. In summary, we present a strategy for identifying and characterizing natural peptides with selective cytotoxicity against cancer cells, which could serve as novel therapeutic agents. Our prediction model can effectively screen new molecules for potential anticancer activity, and the results from in vitro experiments provide compelling evidence of the candidates' anticancer effects and selective cytotoxicity.

Targeting FOS attenuates malignant phenotypes of breast cancer: Evidence from in silico and in vitro studies.

Data retrieved from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases can reveal important information behind molecular biomarkers and their associated oncogenesis. Therefore, this study was based on in silico predictions and in vitro experiments to explore regulatory network associated with breast carcinogenesis. The breast cancer (BC)-related data sets were retrieved from GEO database, followed by differential analysis and protein-protein interaction (PPI) analysis. Then, Fos proto-oncogene, AP-1 transcription factor subunit (FOS)-associated gene network was constructed, and the key gene-related genes in BC were screened by LinkedOmics. Finally, FOS expression was determined in BC tissues and cells, and gain-of-function assays were performed to define the role of FOS in BC cells. It was noted that seven differentially expressed genes (EGR1, RASSF9, FOSB, CDC20, KLF4, PTGS2, and FOS) were obtained from BC microarray data sets. FOS was the gene with the most nodes in PPI analysis. Poor FOS mRNA expression was identified in BC patients. Furthermore, FOS was mainly located in the extracellular matrix and was involved in cell processes. FOS was downregulated in BC tissues and cells, and FOS overexpression restrained the malignant phenotypes of BC cells. Collectively, ectopic expression of FOS curtails the development of BC.

Interactions among mycorrhizal fungi enhance the early development of a Mediterranean orchid.

Orchids depend on mycorrhizal fungi to germinate from seed. While multiple orchid mycorrhizal (OrM) taxa are often found associated with adult orchids, the relative contribution of particular OrM taxa to germination and early orchid development is poorly understood. We isolated 28 OrM fungi associated with the Mediterranean orchid Anacamptis papilionacea and tested the efficiency of five isolates on germination and early development, four belonging to the Tulasnella calospora species complex and one belonging to Ceratobasidium. Co-cultures of varying two-way and three-way combinations of OrM isolates were used in vitro to compare the simultaneous effect on seed germination rate with monocultures. We then tested whether, when given initial priority over other fungi, particular OrM taxa were more effective during the early stages of development. Seedlings germinated with different isolates were transferred to a growth chamber, and either the same or different isolate was added 45 days later. After 3 months, the number of roots, length of the longest root, and tuber area were measured. All OrM fungi resulted in seed germination; however, lower germination rates were associated with the Ceratobasidium isolate compared to the tulasnelloid isolates. There was significant decreased germination in co-culture experiments when the Ceratobasidium isolate was added. Despite being associated with reduced germination rates, the addition of the Ceratobasidium isolate to the seedlings germinated with tulasnelloid strains resulted in significant increased tuber size. Although A. papilionacea associates with many OrM taxa, these results show that OrM fungi may play different roles during orchid germination and early development. Even when given initial priority, other fungi may colonize developing orchids and interact to influence early orchid development.

Quantitative analysis of contribution of mild and moderate hyperthermia to thermal ablation and sensitization of irreversible electroporation of pancreatic cancer cells.

INTRODUCTION: Irreversible electroporation (IRE) is an ablation modality that applies short, high-voltage electric pulses to unresectable cancers. Although considered a non-thermal technique, temperatures do increase during IRE. This temperature rise sensitizes tumor cells for electroporation as well as inducing partial direct thermal ablation. AIM: To evaluate the extent to which mild and moderate hyperthermia enhance electroporation effects, and to establish and validate in a pilot study cell viability models (CVM) as function of both electroporation parameters and temperature in a relevant pancreatic cancer cell line. METHODS: Several IRE-protocols were applied at different well-controlled temperature levels (37 °C ≤ T ≤ 46 °C) to evaluate temperature dependent cell viability at enhanced temperatures in comparison to cell viability at T = 37 °C. A realistic sigmoid CVM function was used based on thermal damage probability with Arrhenius Equation and cumulative equivalent minutes at 43 °C (CEM43°C) as arguments, and fitted to the experimental data using "Non-linear-least-squares"-analysis. RESULTS: Mild (40 °C) and moderate (46 °C) hyperthermic temperatures boosted cell ablation with up to 30% and 95%, respectively, mainly around the IRE threshold Eth,50% electric-field strength that results in 50% cell viability. The CVM was successfully fitted to the experimental data. CONCLUSION: Both mild- and moderate hyperthermia significantly boost the electroporation effect at electric-field strengths neighboring Eth,50%. Inclusion of temperature in the newly developed CVM correctly predicted both temperature-dependent cell viability and thermal ablation for pancreatic cancer cells exposed to a relevant range of electric-field strengths/pulse parameters and mild moderate hyperthermic temperatures.

[Explore the mechanism of astragaloside IV-PESV on proliferation, migration, and autophagy of prostate cancer cells based on the PI3K/AKT signaling pathway].

OBJECTIVE: Explore the effects of Astragaloside IV and Scorpion Venom Peptide on the activity, migration, apoptosis, cell cycle, autophagy, and the expression of proteins related to the PI3K/AKT signaling pathway in prostate cancer cells. METHODS: The human prostate cancer cell lines LNCaP and PC-3 were randomly divided into blank control group, Astragaloside IV group, Scorpion Venom Peptide group, Astragaloside IV-Scorpion Venom Peptide group, and rapamycin (positive drug group). After corresponding drug treatments for 24 hours, logarithmic growth phase tumor cells were collected for testing. Cell proliferation was assessed using a Cell Counting Kit-8 (CCK-8) assay, Transwell assay, apoptosis assay, cell cycle assay, and immunofluorescence analysis were performed to detect the activity and migration capacity of prostate cancer cells in each group, as well as their effects on apoptosis, cell cycle, and the autophagy target LC3. Western blot analysis was employed to measure the protein expression levels of p-PI3K, p-Akt, p-mTOR, Beclin1, LC3, and P62. RESULTS: Compared to the blank control group, the Astragaloside IV-Scorpion Venom Peptide group exhibited a significant decrease in the activity of prostate cancer cells (P<0.05) and a reduction in the cell invasion ability (migration capacity) (P<0.05). The early apoptosis rate (LR), late apoptosis rate (UR), and total apoptosis rate all increased (P<0.05). The proportion of cells in the G1 phase increased (P<0.05), while the proportion in the G2+S phase decreased (P<0.05). The immunofluorescence expression of LC3 significantly increased (P<0.05). The expression of LC3Ⅱ and Beclin1 proteins in prostate cancer cells LNCaP and PC-3 was upregulated (P<0.05), while the expression of P62, p-PI3K, p-AKT, and p-mTOR proteins was downregulated (P<0.05).Astragaloside IV-Scorpion Venom Peptide is superior to the Astragaloside IV group or Scorpion Venom Peptide group alone in inhibiting the activity and migration capacity of prostate cancer cells, suppressing cell mitosis, promoting early apoptosis, upregulating the expression level of LC3, and inhibiting the PI3K/AKT pathway while promoting autophagy (P<0.05). CONCLUSION: The mechanism by which Astragaloside IV-Scorpion Venom Peptide inhibits the proliferation and migration of prostate cancer cells, suppresses cell mitosis, promotes early apoptosis, and enhances autophagy may be related to the inhibition of the PI3K/AKT pathway.

Expression Landscape and Functional Roles of HOXA4 and HOXA5 in Lung Adenocarcinoma.

BACKGROUND: The role of HOXA family genes in the occurrence and progression of a variety of human cancers has been scatteredly reported. However, there is no systematic study on the differential expression, prognostic significance and potential molecular mechanism of HOXA4 and HOXA5 in LUAD. METHODS: In-house immunohistochemistry (IHC), multi-center microarrays, RT-qPCR and RNA-seq data were incorporated for comprehensively evaluating the expression and prognostic value of HOXA4 and HOXA5 in LUAD. The mechanism of HOXA4 and HOXA5 in the formation and development of LUAD was analyzed from multiple aspects of immune correlations, upstream transcriptional regulation, functional states of single cells and co-expressed gene network. The functional roles of HOXA4 and HOXA5 in LUAD were validated by in vitro experiments. RESULTS: As a result, in 3201 LUAD samples and 2494 non-cancer lung samples, HOXA4 and HOXA5 were significantly downexpressed (P < 0.05). The aberrant expression of HOXA5 was significantly correlated with the clinical progression of LUAD (P < 0.05). HOXA5 showed remarkable prognostic value for LUAD patients (P < 0.05). The expression of HOXA4 and HOXA5 in LUAD were negatively correlated with tumor purity and positively correlated with the infiltration of various immune cells such as B cells, T cells and macrophages. HOXA4 and HOXA5 overexpression had notable inhibitory effect on the proliferation, migration and invasion of LUAD cells. CONCLUSIONS: In conclusion, the identified downexpressed HOXA4 and HOXA5 had significant distinguishing ability for LUAD samples and affected the cellular functions of LUAD cells. The low expression of HOXA5 indicated worse overall survival of LUAD patients. Therefore, the two HOXA family genes especially HOXA5 may serve as potential biomarkers for LUAD.

Preliminary study of a novel artificial anal sphincter with perception reconstruction.

BACKGROUND: Artificial anal sphincter (AAS), as an advanced device, has been widely investigated by researchers around world. But the reliability of the structure is still unsatisfactory according to clinical results. What's more, the previous AAS systems are lack the ability of rectal perception as native anal sphincter, which fails to guarantee the safety of the blood supply. In addition, without it, the patient cannot determine when to defecate. METHODS: In order to improve the reliability and safety of current AAS systems, a novel structure AAS system with rectal perception function, based on pressure sensor module, is proposed in this article. The novel AAS system has a closed three-arm clamping mechanism, with transmission structure of cam-follower system. Then, the design, strength check, optimization and force analysis of the proposed mechanism are investigated. After that, to remodel rectal perception function, the novel sensor module system based on strain gauge is established. Finally, in vitro experiments are conducted. RESULTS: In vitro test, the sensor system could monitor the rectal pressure accurately. And when H = 24.6 cm (feeling the urge to have a bowel movement), the clamping pressure is 7.39 kPa. which is also less than the safe pressure 9.33 kPa. CONCLUSIONS: Good performance of the reliability and safety of both novel rectal perception function and new clamping mechanism have been showed.

Association between lincRNA expression and overall survival for patients with triple-negative breast cancer.

PURPOSE: Long intergenic non-coding RNAs (lincRNAs) are increasingly recognized as important regulators for pathogenesis and/or prognosis of breast cancer, including triple-negative breast cancer (TNBC) subtype. However, few previous studies used RNA-sequencing (RNA-Seq) technology, and none included an independent replication. METHODS: To systematically evaluate the association between expression of lincRNAs and TNBC survival, we examined lincRNA expression profiles in TNBC tissues using RNA-Seq data for 200 TNBC patients from the Shanghai Breast Cancer Survival Study (SBCSS) and Southern Community Cohort Study (SCCS). RESULTS: Twenty-five lincRNAs were found to be associated with overall survival (P < 0.05 and no significant heterogeneity across studies at Q statistic P > 0.1), and 61 lincRNAs were associated with disease-free survival (DFS). Among these, two lincRNAs (LINC01270 and LINC00449) were significantly associated with both worse overall survival and DFS and were expressed at significantly higher levels in tumor tissues compared with adjacent normal breast tissues (log2[Fold Change] > 0.5 and FDR < 0.05). We further evaluated the potential functions of LINC01270 and LINC00449 using in vitro functional experiments and found that siRNA-mediated knockdown of LINC01270 and LINC00449 expression significantly decreased cell viability, colony formation and cell migration ability in TNBC cells (P < 0.05). CONCLUSIONS: Evidence from observational studies and in vitro experiments indicates that LINC00449 and LINC01270 may be prognostic biomarkers for TNBC.

A temperature model for laser lithotripsy.

OBJECTIVE: To derive and validate a mathematical model to predict laser-induced temperature changes in a kidney during kidney stone treatment. METHODS: A simplified mathematical model to predict temperature change in the kidney for any given renal volume, irrigation flow rate, irrigation fluid temperature, and laser power was derived. We validated our model with matched in vitro experiments. RESULTS: Excellent agreement between the mathematical model predictions and laboratory data was obtained. CONCLUSION: The model obviates the need for repeated experimental validation. The model predicts scenarios where risk of renal tissue damage is high. With real-time knowledge of flow rate, irrigating fluid temperature and laser usage, safety warning levels could be predicted. Meanwhile, clinicians should be aware of the potential risk from thermal injury and take measures to reduce the risk, such as using room temperature irrigation fluid and judicious laser use.

Comparison of ablation characteristics of three different radiofrequency applicators in renal sympathetic denervation.

OBJECTIVE: Renal sympathetic denervation (RDN) is an alternative treatment for resistant hypertension (RH). This study aims to compare ablation effects using three radiofrequency applicators (i.e., balloon-based four electrodes, spiral and monopolar devices). METHODS: An idealized three-dimensional model of the renal artery was established using COMSOL Multiphysics to mimic radiofrequency ablation (RFA). Radiofrequency (RF) energy was delivered to the tissue at the same simulation settings, i.e., 4, 6, and 8 W for 60 s, using the three abovementioned RF applicators. The temperature distribution in the tissue was calculated using the coupled electrical-thermal-fluid finite element method. Lesion borders were defined using 50 °C isotherms. The maximum lesion depth, width, area, and circumferential coverage rate were compared among the three applicators at a blood flow of 0.4 m/s. Monopolar RF ablations in a renal artery phantom model were performed to validate the reliability of the simulation method. RESULTS: The balloon-based system yields greater lesion depths and widths compared with spiral and monopolar denervation under the same power. The range of maximum lesion depth is 1.58-3.11 mm for balloon-based RDN, 0.90-1.81 mm for spiral RDN and 1.12-2.38 mm for monopolar RDN, at a power of 4-8 W. The corresponding ranges of maximum lesion width are 2.22-5.73, 1.48-3.54, and 1.93-5.31 mm, respectively, and the circumferential coverage rates of the renal artery are 41.43%-91.99%, 31.71%-66.23%, and 9.55%-23.06%, respectively. The average velocity after balloon-based, spiral, and monopolar RDN increases by 3, 5, and 1 cm/s, respectively. The validation of the computer model offered prediction errors are <5% in terms of temperature at different locations (i.e., 2, 4, and 8 mm). CONCLUSIONS: In terms of lesion size, balloon-based RDN appears to be the best option for the treatment of RH. However, the change in flow velocity in the arterial flow field suggests that its hemodynamic changes must be prioritized for investigating its safety. Although spiral catheter ablation yields the smallest lesion size and a significant change in flow velocity in the flow field, its coverage rate is larger than that of monopolar RDN; compared with balloon-based RDN, it did not obstruct most of the blood flow.

An artificial anal sphincter based on a novel clamping mechanism: Design, analysis, and testing.

An artificial anal sphincter is a device to help patients with fecal incontinence rebuild the ability to control the excrement through the anus. In this article, an artificial anal sphincter based on a novel clamping mechanism (AASNCM) is proposed to improve the safety and reliability. The AASNCM, which is powered by a transcutaneous energy transfer system, consists of a novel clamping mechanism, a receiving coil and a control unit. According to design requirements, the novel clamping mechanism model was established. After that, its kinematics and dynamics were analyzed. The results of force tests on the prototype AASNCM show that the maximum values of clamping force and expanding force are 15.859 and 31.029 N, respectively. Comparing the experimental results with theoretical analysis, a good match can be concluded. Finally, in vitro experiments were conducted, and have verified the safety and reliability of the proposed AASNCM.

ß-Carbolines in Experiments on Laboratory Animals.

Some studies have ascribed a protective effect against neurodegenerative diseases to the ß-carbolines harman (H) and norharman (NH), which occur mostly in coffee and coffee substitutes. We determined the concentrations of ß-carbolines and undesirable compounds (such as acrylamide) in roasted coffee substitute ingredients and found that chicory coffee was optimal. Two in vivo experiments were conducted with seventeen-month-old male Sprague Dawley rats fed a diet with the addition of pure carboline standards in the first stage, and chicory in the second. We observed an increase in the level of H and NH in blood plasma, as well as higher activity of animals in the battery behavioral test, particularly in the second stage. The results of in vitro studies-particularly the level of the expression in brain tissue of genes associated with aging processes and neurodegenerative diseases-clearly show the benefits of a diet rich in ß-carbolines.

Cyclodextrin Encapsulated pH Sensitive Dyes as Fluorescent Cellular Probes: Self-Aggregation and In Vitro Assessments.

We have designed and synthesized a series of novel, supramolecular, long-lived fluorescent probes based on the host-guest inclusion complexes formation between fluorescent indolizinyl-pyridinium salts and ß-cyclodextrin. Fluorescence and electrospray ionisation mass spectrometry experiments, supported by theoretical molecular docking studies, were utilized in the monitoring of the inclusion complexes formation, evidencing the appearance of corresponding 1:1 and 1:2 species. Additionally, the influence of the guest molecule over the aggregation processes of the cyclodextrin inclusion complexes was investigated by transmission electron microscopy. The absence of cytotoxicity, cellular permeability, long-lived intracellular fluorescence, and in time specific accumulation within acidic organelles identified the investigated supramolecular entities as remarkable candidates for intracellular fluorescence probes. Co-staining experiments using specific organelle markers revealed the fact that, after a 24-h incubation period, the inclusion complexes accumulate predominantly in lysosomes rather than in mitochondria. This study opens new possibilities for a broad range of fluorescent dyes with solubility and high toxicity issues, able to form inclusion complexes with ß-cyclodextrin, to be tested as intracellular fluorescence probes.

3-Aryl-4-nitrobenzothiochromans S,S-dioxide: From Calcium-Channel Modulators Properties to Multidrug-Resistance Reverting Activity.

Our research groups have been involved for many years in studies aimed at identifying new active organic compounds endowed with pharmacological properties. In this work, we focused our attention on the evaluation of cardiovascular and molecular drug resistance (MDR) reverting activities of some nitrosubstituted sulphur-containing heterocycles. Firstly, we have examined the effects of 4-nitro-3-(4-methylphenyl)-3,6-dihydro-2H-thiopyran S,S-dioxide 5, and have observed no activity. Then we have extended our investigation to the 3-aryl-4-nitrobenzothiochromans S,S-dioxide 6 and 7, and have observed an interesting biological profile. Cardiovascular activities were assessed for all compounds using ex vivo studies, while the MDR reverting effect was evaluated only for selected compounds using tumor cell lines. All compounds were shown to affect cardiovascular parameters. Compound 7i exerted the most effect on negative inotropic activity, while 6d and 6f could be interesting molecules for the development of more active ABCB1 inhibitors. Both 6 and 7 represent structures of large possible biological interest, providing a scaffold for the identification of new ABCB1 inhibitors.

Millimeter-Wave Heating in In Vitro Studies: Effect of Convection in Continuous and Pulse-Modulated Regimes.

Shallow penetration of millimeter waves (MMW) and non-uniform illumination in in vitro experiments result in a non-uniform distribution of the specific absorption rate (SAR). These SAR gradients trigger convective currents in liquids affecting transient and steady-state temperature distributions. We analyzed the effect of convection on temperature dynamics during MMW exposure in continuous-wave (CW) and pulsed-wave (PW) amplitude-modulated regimes using micro-thermocouples. Temperature rise kinetics are characterized by the occurrence of a temperature peak that shifts to shorter times as the SAR of the MMW exposure increases and precedes initiation of convection in bulk. Furthermore, we demonstrate that the liquid volume impacts convection. Increasing the volume results in earlier triggering of convection and in a greater cooling rate after the end of the exposure. In PW regimes, convection strongly depends on the pulse duration that affects the heat pulse amplitude and cooling rate. The latter results in a change of the average temperature in PW regime. Bioelectromagnetics. 2019;40:553-568. © 2019 Bioelectromagnetics Society.

Synthesis, characterization, molecular modelling and biological evaluation of thieno-pyrimidinone methanesulphonamide thio-derivatives as non-steroidal anti-inflammatory agents.

This study reports the synthesis, molecular docking and biological evaluation of eight (5-8 and 5a-8a) newly synthesized thieno-pyrimidinone methanesulphonamide thio-derivatives. The synthetic route used to prepare the new isomers thioaryl and thio-cycloesyl derivatives of the heterocyclic system 6-phenylthieno[3,2]pyrimidinone was economically and environmentally very advantageous and characterized by the simplicity of procedure, reduction in isolation steps, purification phases, time, costs and waste production. The study in silico for the evaluation of cyclooxygenase (COX)-1 and COX-2 selective inhibition was carried out by AutoDock Vina, an open-source program for doing molecular docking which predicts the preferred orientation of one molecule to a second when bound to each other to form a stable complex. The research in vitro for the biological evaluation was performed by using human cartilage and chondrocytes cultures treated with 10 ng/mL of interleukin-1beta as inflammation models. The anti-inflammatory activity of each new compound at the concentration of 10 µmol/L was determined by assaying COX-2, inducible nitric oxide synthetase (iNOS) and intercellular adhesion molecule 1 (ICAM 1) through Western blot. The examined derivatives showed interesting pharmacological activity, and the compound N-[2-[2,4-difluorophenyl)thio]-4-oxo-6-phenylthieno[3,2-d]pyridine-34H-yl]methanesulphonamide (7) was excellent COX-2 inhibitor. In agreement with the biological data, compound 7 was able to fit into the active site of COX-2 with highest interaction energy. These results can support the design of novel specific inhibitors of COX-2 by the comparative modelling of COX-1 and COX-2 enzymes with the available pharmacophore.

Electrochemical aptamer-based biosensor developed to monitor PSA and VEGF released by prostate cancer cells.

Early prostate cancer (PCa) diagnostic is crucial to enhance patient survival rates; besides, non-invasive platforms have been developed worldwide in order to precisely detect PCa biomarkers. Therefore, the aim of the present study is to develop a new aptamer-based biosensor through the self-assembling of thiolated aptamers for PSA and VEGF on the top of gold electrodes. This biosensor was tested in three prostate cell lines (RWPE-1, LNCaP and PC3). The results evidenced a stable and sensitive sensor presenting wide linear detection ranges (0.08-100 ng/mL for PSA and 0.15 ng-100 ng/mL for VEGF). Therefore, the aptasensor was able to detect the patterns of PSA and VEGF released in vitro by PCa cells, which gave new insights about the prostate cancer protein dynamics. Thus, it could be used as a non-invasive PCa clinical diagnosis instrument in the near future. Graphical Abstract Overview of the experimental design applied to the aptamer-based electrochemical sensor self-assembled on the thiolated hairpin structure. A filter membrane was added on top of working electrode to provide the cell-attachment surface after aptamer incubation, without compromising the aptamer layer. The pore membrane allowed target proteins to pass to the aptamer surface; the MCH backfilling avoided unspecific protein binding to the gold electrode surface.