Search

Prostate cancer (PC) is one of the most commonly diagnosed tumours among men. Second-generation androgen receptor axis-targeted (ARAT) agents, namely abiraterone acetate (AbA) and enzalutamide (ENZ), are currently used in the management of metastatic castration-resistant PC (mCRPC). However, the treatment is challenging due to the lack of prognostic biomarkers. Meanwhile, single-nucleotide polymorphisms (SNPs) have emerged as potential prognostic indicators of mCRPC. Thus, this study evaluated the impact of relevant SNPs on the treatment outcomes of 123 mCRPC patients enrolled in a hospital-based cohort study. The CYP17A1 rs2486758 C allele was associated with a 50% reduction in the risk of developing castration resistance (hazard ratio (HR) = 0.55; p = 0.003). Among patients without metastasis at tumour diagnosis and under AbA, a marginal association between YBX1 rs10493112 and progression-free survival was detected (log-rank test, p = 0.056). In the same subgroup, significant associations of HSD3B1 rs1047303 (CC/CA vs. AA; HR = 3.41; p = 0.025), YBX1 rs12030724 (AT vs. AA; HR = 3.54; p = 0.039) and YBX1 rs10493112 (log-rank test, p = 0.041; CC vs. AA/AC; HR = 3.22; p = 0.053) with overall survival were also observed, which were confirmed by multivariate Cox analyses. Although validation with larger cohorts is required, these findings suggest that SNPs could enhance the prognosis assessment of mCRPC patients, leading to a more personalised treatment. [ABSTRACT FROM AUTHOR]

Additive manufacturing (AM) plays a crucial role in the development of NiTi alloys, enabling the creation of complex and customized structures while optimizing properties for various biomedical and industrial applications. The aim of this paper was to investigate the influence of laser scanning speed on laser-assisted reactive sintering of a mixture of No and Ti powders. The samples were sintered at two different beam speeds, 4 and 5 4 mm/s and their morphological and microstructural characteristics were investigated. Scanning electron microscopy with energy dispersive X-ray spectroscopy (SEM/EDX) and X-ray diffraction (XRD) analyses revealed the presence of intermetallic compounds rich in Ni and Ti for both scanning speeds; however, the scanning speed of 5 mm/s produced a microstructure with greater porosity, leading to a sintered body with poorer consolidation. Thus, employing a slower beam scanning of 4 mm/s seems to be a better alternative in the laser-assisted reactive sintering of NiTi alloys. [ABSTRACT FROM AUTHOR]

There are inconclusive claims in the scientific literature that the species Trema micranthum, widely distributed throughout the Brazilian territory, may produce phytocannabinoids, potentially serving as an alternative to Cannabis sativa. In this study, we conducted a comprehensive investigation to assess the presence of phytocannabinoids in two Trema micranthum samples collected in the Midwest region of Brazil. In trying to detect cannabinoids in T. micranthum, a recommended cannabis screening test was employed, the Fast Blue BB Salt (FBBBS) colorimetric assay, followed by thin-layer chromatography (TLC) and instrumental techniques: high-performance liquid chromatography coupled to diode array detector (HPLC-DAD) and gas chromatography coupled to mass spectrometry (GC-MS). When employed without chloroform extraction, the FBBBS reagent yielded positive results for extracts from all parts of T. micranthum (leaves, branches, fruits, and inflorescences). However, these initial positive results from the FBBBS test, suggesting the presence of cannabinoids, were not corroborated by FBBBS followed by chloroform extraction, TLC, or the instrumental techniques used in this study. These additional outcomes suggest that the positive FBBBS test results were likely due to the presence of other phenolic compounds rather than phytocannabinoids. For example, the presence of vitexin-like compounds in T. micranthum extracts might explain the positive FBBBS test results. Therefore, new assertions that T. micranthum produces cannabinoids will require the support of more selective experiments to avoid false-positive claims based on less selective screening tests. [ABSTRACT FROM AUTHOR]

Simple Summary: Cancer stands as a major public health concern worldwide, and a significant proportion of survivors are affected by recurrent and usually unrelieved cancer pain. The participation of ion channels in cancer pain's initiation and maintenance is well-described; however, the evidence on the contribution of transient receptor potential vanilloid 4 channels is scarce. The limited studies published to date encountered enhanced TRPV4 expression in cancer-induced bone pain (CIBP), perineural, and orofacial cancer models, increasing pain perception. These outcomes support the hypothesis that the modulation of TRPV4 channels can be targeted as a novel therapeutic approach for treating difficult pain. This review summarizes the role of TRPV4 in cancer etiology and cancer-induced pain mechanisms, as well as the current status of the clinical research. Despite the unique and complex nature of cancer pain, the activation of different ion channels can be related to the initiation and maintenance of pain. The transient receptor potential vanilloid 4 (TRPV4) is a cation channel broadly expressed in sensory afferent neurons. This channel is activated by multiple stimuli to mediate pain perception associated with inflammatory and neuropathic pain. Here, we focused on summarizing the role of TRPV4 in cancer etiology and cancer-induced pain mechanisms. Many studies revealed that the administration of a TRPV4 antagonist and TRPV4 knockdown diminishes nociception in chemotherapy-induced peripheral neuropathy (CIPN). Although the evidence on TRPV4 channels' involvement in cancer pain is scarce, the expression of these receptors was reportedly enhanced in cancer-induced bone pain (CIBP), perineural, and orofacial cancer models following the inoculation of tumor cells to the bone marrow cavity, sciatic nerve, and tongue, respectively. Effective pain management is a continuous problem for patients diagnosed with cancer, and current guidelines fail to address a mechanism-based treatment. Therefore, examining new molecules with potential antinociceptive properties targeting TRPV4 modulation would be interesting. Identifying such agents could lead to the development of treatment strategies with improved pain-relieving effects and fewer adverse effects than the currently available analgesics. [ABSTRACT FROM AUTHOR]

NiTi shape memory alloy films were prepared by magnetron sputtering using a compound NiTi target and varying deposition parameters, such as power density, pressure, and deposition time. To promote crystallization, the films were heat treated at a temperature of 400 °C for 1 h. For the characterization, scanning electron microscopy, energy dispersive X-ray spectroscopy, atomic force microscopy, synchrotron X-ray diffraction, and nanoindentation techniques were used on both as-deposited and heat-treated films. Apart from the morphology and hardness of the as-deposited films that depend on the deposition pressure, the power applied to the target and the deposition pressure did not seem to significantly influence the characteristics of the NiTi films studied. After heat treatment, austenitic (B2) crystalline superelastic films with exceptionally high nickel content (~60 at.%) and vein-line cross-section morphology were produced. The crystallization of the films resulted in an increase in hardness, Young's modulus, and elastic recovery. [ABSTRACT FROM AUTHOR]

Neuropathic pain is a chronic pain caused by a disease or damage to the somatosensory nervous system. The knowledge about the complete mechanisms is incomplete, but the role of oxidative compounds has been evaluated. In this context, we highlight the transient potential receptor vanilloid 4 (TRPV4), a non-selective cation channel, that can be activated by oxidated compounds. In clinical trials, the TRPV4 antagonist (GSK2798745) has been well-tolerated in healthy volunteers. The TRPV4 activation by oxidative compounds, such as hydrogen peroxide (H2O2) and nitric oxide (NO), has been researched in neuropathic pain models. Thus, the modulation of TRPV4 activation by decreasing oxidated compounds could represent a new pharmacological approach for neuropathic pain treatment. Most models evaluated the TRPV4 using knockout mice, antagonist or antisense treatments and detected mechanical allodynia, hyposmotic solution-induced nociception and heat hyperalgesia, but this channel is not involved in cold allodynia. Only H2O2 and NO were evaluated as TRPV4 agonists, so one possible target to reduce neuropathic pain should focus on reducing these compounds. Therefore, this review outlines how the TRPV4 channel represents an innovative target to tackle neuropathic pain signaling in models induced by trauma, surgery, chemotherapy, cancer, diabetes and alcohol intake. [ABSTRACT FROM AUTHOR]

Clinical and experimental data indicate that severe acute respiratory syndrome coronavirus (SARS-CoV)-2 infection is associated with significant changes in the composition and function of intestinal microbiota. However, the relevance of these effects for SARS-CoV-2 pathophysiology is unknown. In this study, we analyzed the impact of microbiota depletion after antibiotic treatment on the clinical and immunological responses of K18-hACE2 mice to SARS-CoV-2 infection. Mice were treated with a combination of antibiotics (kanamycin, gentamicin, metronidazole, vancomycin, and colistin, Abx) for 3 days, and 24 h later, they were infected with SARS-CoV-2 B lineage. Here, we show that more than 80% of mice succumbed to infection by day 11 post-infection. Treatment with Abx had no impact on mortality. However, Abx-treated mice presented better clinical symptoms, with similar weight loss between infected–treated and non-treated groups. We observed no differences in lung and colon histopathological scores or lung, colon, heart, brain and kidney viral load between groups on day 5 of infection. Despite some minor differences in the expression of antiviral and inflammatory markers in the lungs and colon, no robust change was observed in Abx-treated mice. Together, these findings indicate that microbiota depletion has no impact on SARS-CoV-2 infection in mice. [ABSTRACT FROM AUTHOR]

The present study shows a comparison between two sintering processes, microwave and conventional sintering, for the manufacture of NiTi porous specimens starting from powder mixtures of nickel and titanium hydrogenation–dehydrogenation (HDH) milled by mechanical alloying for a short time (25 min). The samples were sintered at 850 °C for 15 min and 120 min, respectively. Both samples exhibited porosity, and the pore size results are within the range of the human bone. The NiTi intermetallic compound (B2, R-phase, and B19′) was detected in both sintered samples through X-ray diffraction (XRD) and electron backscattering diffraction (EBSD) on scanning electron microscopic (SEM). Two-step phase transformation occurred in both sintering processes with cooling and heating, the latter occurring with an overlap of the peaks, according to the differential scanning calorimetry (DSC) results. From scanning electron microscopy/electron backscatter diffraction, the R-phase and B2/B19′ were detected in microwave and conventional sintering, respectively. The instrumented ultramicrohardness results show the highest elastic work values for the conventionally sintered sample. It was observed throughout this investigation that using mechanical alloying (MA) powders enabled, in both sintering processes, good results, such as intermetallic formation and densification in the range for biomedical applications. [ABSTRACT FROM AUTHOR]

Actuators using Shape Memory Alloy (SMA) springs could operate in different mechanical systems requiring geometric flexibility and high performance. The aim of the present study is to highlight the potential of these actuators, using their dimensional variations resulting from the phase transformations of NiTi springs (SMA) to make the movements of the system's mobile components reversible. This reversibility is due to thermal-induced martensitic transformation of NiTi springs. The transformation promotes the extended and retracted of the springs as the phase changing (martensite–austenite) creates movement in part of the system. Therefore, the phase transition temperatures of NiTi, evaluated by differential scanning calorimetry (DSC), are required to control the dimensional variation of the spring. The influence of the number of springs in the system, as well as how impacts on the reaction time were evaluated. The different numbers of springs (two, four, and six) and the interspaces between them made it possible to control the time and the final angle attained in the mobile part of the system. Mechanical resistance, maximum angle, and the system's reaction time using different NiTi springs highlight the role of the actuators. Fused Deposition Modelling (FDM)/Material Extrusion (MEX) or Selective Laser Sintering (SLS) was selected for shaping the composite matrix system. A new prototype was designed and developed to conduct tests that established the relationship between the recoverable deformation of the matrix suitable for the application as well as the number and distribution of the actuators. [ABSTRACT FROM AUTHOR]

Polydimethylsiloxane (PDMS) is ubiquitously used in microfluidics. However, PDMS is porous and hydrophobic, potentially leading to small molecule partitioning. Although many studies addressed this issue and suggested surface/bulk modifications to overcome it, most were not quantitative, did not address which variables besides hydrophobicity governed molecule absorption, and no modification has been shown to completely obviate it. We evaluated qualitatively (confocal microscopy) and quantitatively (fluorescence spectroscopy) the effects of solute/solvent pairings, concentration, and residence time on molecule partitioning into PDMS. Additionally, we tested previously reported surface/bulk modifications, aiming to determine whether reduced PDMS hydrophobicity was stable and hindered molecule partitioning. Partitioning was more significant at lower concentrations, with the relative concentration of rhodamine-B at 20 µM remaining around 90% vs. 10% at 1 µM. Solute/solvent pairings were demonstrated to be determinant by the dramatically higher partitioning of Nile-red in a PBS-based solvent as opposed to ethanol. A paraffin coating slightly decreased the partitioning of Nile-red, and a sol–gel modification hindered the rhodamine-B diffusion into the PDMS bulk. However, there was no direct correlation between reduced surface hydrophobicity and molecule partitioning. This work highlighted the need for pre-assessing the absorption of test molecules into the microfluidic substrates and considering alternative materials for fabrication. [ABSTRACT FROM AUTHOR]

This study applies a methodology to evaluate the ecotoxicological potential of raw materials and cement-based construction materials. In this study, natural aggregates and Portland cement were replaced with non-conventional recycled concrete aggregates (RA) and fly ash (FA), respectively, in the production of two concrete products alternative to conventional concrete (used as reference). The experimental program involved assessing both the chemical properties (non-metallic and metallic parameters) and ecotoxicity data (battery of tests with the luminescent bacterium Vibrio fischeri, the freshwater crustacean Daphnia magna, and the yeast Saccharomyces cerevisiae) of eluates obtained from leaching tests of RA, FA, and the three concrete mixes. Even though the results indicated that RA and FA have the ability to release some chemicals into the water and induce its alkalinisation, the respective eluate samples presented no or low levels of potential ecotoxicity. However, eluates from concrete mixes produced with a replacement ratio of Portland cement with 60% of FA and 100% of natural aggregates and produced with 60% of FA and 100% of RA were classified as clearly ecotoxic mainly towards Daphnia magna mobility. Therefore, raw materials with weak evidences of ecotoxicity could lead to the production of concrete products with high ecotoxicological potential. Overall, the results obtained highlight the importance of integrating data from the chemical and ecotoxicological characterization of materials' eluate samples aiming to assess the possible environmental risk of the construction materials, namely of incorporating non-conventional raw materials in concrete, and contributing to achieve construction sustainability. [ABSTRACT FROM AUTHOR]

Innovation in construction materials (CM) implies changing their composition by incorporating raw materials, usually non-traditional ones, which confer the desired characteristics. However, this practice may have unknown risks. This paper discusses the ecotoxicological potential associated with raw and construction materials, and proposes and applies a methodology for the assessment of their ecotoxicological potential. This methodology is based on existing laws, such as Regulation (European Commission) No. 1907/2006 (REACH—Registration, Evaluation, Authorization and Restriction of Chemicals) and Regulation (European Commission) No. 1272/2008 (CLP—Classification, Labelling and Packaging). Its application and validation showed that raw material without clear evidence of ecotoxicological potential, but with some ability to release chemicals, can lead to the formulation of a CM with a slightly lower hazardousness in terms of chemical characterization despite a slightly higher ecotoxicological potential than the raw materials. The proposed methodology can be a useful tool for the development and manufacturing of products and the design choice of the most appropriate CM, aiming at the reduction of their environmental impact and contributing to construction sustainability. [ABSTRACT FROM AUTHOR]

The structural and thermophysical characteristics of an Ni-rich NiTi alloy rod produced on a laboratory scale was studied. The soak temperature of the solution heat-treatment steps above 850 °C taking advantage of the precipitate dissolution to provide a matrix homogenization, but it takes many hours (24 to 48) when used without thermomechanical steps. Therefore, the suitable reheating to apply between the forging process steps is very important, because the product's structural characteristics are dependent on the thermomechanical processing history, and the time required to expose the material to high temperatures during the processing is reduced. The structural characteristics were investigated after solution heat treatment at 900 °C and 950 °C for 120 min, and these heat treatments were compared with as-forged sample structural characteristics (one hot deformation step after 800 °C for a 30 min reheat stage). The phase-transformation temperatures were analyzed through differential scanning calorimetry (DSC), and the structural characterization was performed through synchrotron radiation-based X-ray diffraction (SR-XRD) at room temperature. It was observed that the solution heat treatment at 950 °C/120 min presents a lower martensitic reversion finish temperature (Af); the matrix was fully austenitic; and it had a hardness of about 226 HV. Thus, this condition is the most suitable for the reheating stages between the hot forging-process steps to be applied to this alloy to produce materials that can display a superelasticity effect, for applications such as crack sensors or orthodontic archwires. [ABSTRACT FROM AUTHOR]

The interaction between the stress-induced martensitic transformation and resistivity behavior of superelastic NiTi shape memory alloy (SMA) was studied. Strain-controlled low-cycle fatigue up to 6% was monitored by in situ electrical resistivity measurements. The experimental results show that a great motion of martensite fronts results in a significant accumulation of defects, as evidenced by transmission electron microscopy (TEM), before and after the tensile cycles. This gives rise to an overall increase of the resistivity values up to the maximum deformation. Therefore, the research suggests that shape memory alloy wire has great potential as a stress sensor inside bulk materials. [ABSTRACT FROM AUTHOR]

This study aims to provide new insights into transcriptome and miRome modifications occurring in cardiac reverse remodelling (RR) upon left ventricle pressure-overload relief in mice. Pressure-overload was established in seven-week-old C57BL/6J-mice by ascending aortic constriction. A debanding (DEB) surgery was performed seven weeks later in half of the banding group (BA). Two weeks later, cardiac function was evaluated through hemodynamics and echocardiography, and the hearts were collected for histology and small/bulk-RNA-sequencing. Pressure-overload relief was confirmed by the normalization of left-ventricle-end-systolic-pressure. DEB animals were separated into two subgroups according to the extent of cardiac remodelling at seven weeks and RR: DEB1 showed an incomplete RR phenotype confirmed by diastolic dysfunction persistence (E/e' ≥ 16 ms) and increased myocardial fibrosis. At the same time, DEB2 exhibited normal diastolic function and fibrosis, presenting a phenotype closer to myocardial recovery. Nevertheless, both subgroups showed the persistence of cardiomyocytes hypertrophy. Notably, the DEB1 subgroup presented a more severe diastolic dysfunction at the moment of debanding than the DEB2, suggesting a different degree of cardiac remodelling. Transcriptomic and miRomic data, as well as their integrated analysis, revealed significant downregulation in metabolic and hypertrophic related pathways in DEB1 when compared to DEB2 group, including fatty acid β-oxidation, mitochondria L-carnitine shuttle, and nuclear factor of activated T-cells pathways. Moreover, extracellular matrix remodelling, glycan metabolism and inflammation-related pathways were up-regulated in DEB1. The presence of a more severe diastolic dysfunction at the moment of pressure overload-relief on top of cardiac hypertrophy was associated with an incomplete RR. Our transcriptomic approach suggests that a cardiac inflammation, fibrosis, and metabolic-related gene expression dysregulation underlies diastolic dysfunction persistence after pressure-overload relief, despite left ventricular mass regression, as echocardiographically confirmed. [ABSTRACT FROM AUTHOR]

The structural and thermophysical characteristics of an Ni-rich NiTi alloy rod produced on a laboratory scale was studied. The soak temperature of the solution heat-treatment steps above 850 °C taking advantage of the precipitate dissolution to provide a matrix homogenization, but it takes many hours (24 to 48) when used without thermomechanical steps. Therefore, the suitable reheating to apply between the forging process steps is very important, because the product's structural characteristics are dependent on the thermomechanical processing history, and the time required to expose the material to high temperatures during the processing is reduced. The structural characteristics were investigated after solution heat treatment at 900 °C and 950 °C for 120 min, and these heat treatments were compared with as-forged sample structural characteristics (one hot deformation step after 800 °C for a 30 min reheat stage). The phase-transformation temperatures were analyzed through differential scanning calorimetry (DSC), and the structural characterization was performed through synchrotron radiation-based X-ray diffraction (SR-XRD) at room temperature. It was observed that the solution heat treatment at 950 °C/120 min presents a lower martensitic reversion finish temperature (A f ); the matrix was fully austenitic; and it had a hardness of about 226 HV. Thus, this condition is the most suitable for the reheating stages between the hot forging-process steps to be applied to this alloy to produce materials that can display a superelasticity effect, for applications such as crack sensors or orthodontic archwires.