LGYSB:Nd─High-Performance Lasing in the Near-Infrared Region.

Three incongruent melting LawNdxGdyYzSc4-w-x-y-z(BO3)4 (LGYSB:Nd) crystals with different Y concentrations (z = 0.15, 0.05, and 0.025) have been grown by the Czochralski method for the first time. The LGYSB:Nd-type crystals exhibit an acentric structure similar to that of the natural mineral huntite CaMg3(CO3)4, with space group R32. The composition of the LGYSB:Nd_3 (z = 0.025) crystal grown from the starting melt composition La0.628Gd0.547Y0.025Nd0.05Sc2.75(BO3)4 was measured by inductively coupled plasma mass spectrometry method, and it was found to be La0.6794Gd0.4105Y0.0178Nd0.0381Sc2.8542(BO3)4. The transversal spatial distribution of the refractive index in the LGYSB:Nd_3 crystal was investigated. Third-order nonlinear optical susceptibility χ(3) of the LGYSB:Nd_3 crystal was determined from third-harmonic generation experiments with ultrashort (fs) laser pulses. The optical transmission spectrum was measured in the range of 200-2000 nm. The absorption cross-section at 808 nm in σ-polarization was determined to be 1.18 × 10-19 cm2 for the LGYSB:Nd_3 crystal. The 10K absorption spectra revealed that the Nd3+ ions occupy only La3+ cationic sites in the LGYSB host matrix. The emission cross-section at 1064 nm in σ-polarization was determined to be σem(σ) = 1.74 × 10-19 cm2 for the LGYSB:Nd_3 crystal. The fluorescence lifetime was found to be τ = 115 µs for all of the LGYSB:Nd crystals. The LGYSB:Nd_3 laser was operated at an emission wavelength of 1062 nm with very high slope efficiencies of ηsa = 0.74 and ηsa = 0.64 in quasi-cw and cw regimes, respectively.

Zinc/Cerium-Substituted Magnetite Nanoparticles for Biomedical Applications.

Numerous studies have reported the possibility of enhancing the properties of materials by incorporating foreign elements within their crystal lattice. In this context, while magnetite has widely known properties that have been used for various biomedical applications, the introduction of other metals within its structure could prospectively enhance its effectiveness. Specifically, zinc and cerium have demonstrated their biomedical potential through significant antioxidant, anticancer, and antimicrobial features. Therefore, the aim of the present study was to develop a series of zinc and/or cerium-substituted magnetite nanoparticles that could further be used in the medical sector. The nanostructures were synthesized through the co-precipitation method and their morpho-structural characteristics were evaluated through X-ray diffraction (XRD), inductively coupled plasma mass spectrometry (ICP-MS), X-ray photoelectron spectroscopy (XPS), dynamic light scattering (DLS), zeta potential, scanning electron microscopy (SEM), and energy dispersive X-ray spectroscopy (EDX) analyses. Furthermore, the nanostructures were subjected to a ROS-Glo H2O2 assay for assessing their antioxidant potential, MTT assay for determining their anticancer effects, and antimicrobial testing against S. aureus, P. aeruginosa, and C. albicans strains. Results have proven promising for future biomedical applications, as the nanostructures inhibit oxidative stress in normal cells, with between two- and three-fold reduction and cell proliferation in tumor cells; a two-fold decrease in cell viability and microbial growth; an inhibition zone diameter of 4-6 mm and minimum inhibitory concentration (MIC) of 1-2 mg/mL.

PCR Array Profiling of miRNA Expression Involved in the Differentiation of Amniotic Fluid Stem Cells toward Endothelial and Smooth Muscle Progenitor Cells.

Differentiation of amniotic fluid stem cells (AFSCs) into multiple lineages is controlled by epigenetic modifications, which include DNA methylation, modifications of histones, and the activity of small noncoding RNAs. The present study investigates the role of miRNAs in the differentiation of AFSCs and addresses how their unique signatures contribute to lineage-specific differentiation. The miRNA profile was assessed in AFSCs after 4 weeks of endothelial and muscular differentiation. Our results showed decreased expression of five miRNAs (miR-18a-5p, miR-125b-5p, miR-137, miR-21-5p, and let-7a) and increased expression of twelve miRNAs (miR-134-5p, miR-103a-3p, let-7i-5p, miR-214-3p, let-7c-5p, miR-129-5p, miR-210-3p, let-7d-5p, miR-375, miR-181-5p, miR-125a-5p, and hsa-let-7e-5p) in endothelial progenitor cells (EPCs) compared with undifferentiated AFSCs. AFSC differentiation into smooth muscle revealed notable changes in nine out of the 84 tested miRNAs. Among these, three miRNAs (miR-18a-5p, miR-137, and sa-miR-21-5p) were downregulated, while six miRNAs (miR-155-5p, miR-20a-5p, let-7i-5p, hsa-miR-134-5p, hsa-miR-214-3p, and hsa-miR-375) exhibited upregulation. Insights from miRNA networks promise future advancements in understanding and manipulating endothelial and muscle cell dynamics. This knowledge has the potential to drive innovation in areas like homeostasis, growth, differentiation, and vascular function, leading to breakthroughs in biomedical applications and therapies.

High Filamin a Expression in Adrenocortical Carcinomas Is Associated with a Favourable Tumour Behaviour: A European Multicentric Study.

The insulin-like growth factor 2 (IGF2) promotes cell growth by overactivating the IGF system in an autocrine loop in adrenocortical carcinomas (ACCs). The cytoskeleton protein filamin A (FLNA) acts as a repressor of IGF2 mitogenic signalling in ACC cells. The aims of this study were to test FLNA expression by immunohistochemistry in 119 ACCs and 26 adrenocortical adenomas (ACAs) and to evaluate its relationship with clinicopathological features and outcome in ACCs. We found that 71.4% of ACCs did not express FLNA, whereas FLNA absence was a rare event in ACAs (15.4%, p < 0.001 vs. ACCs). In addition, the expression of FLNA was associated with a less aggressive tumour behaviour in ACCs. Indeed, the subgroup of ACCs with high FLNA showed a lower ENSAT stage, Weiss score, and S-GRAS score compared to ACCs with low FLNA expression (p < 0.05). Moreover, patients with high FLNA had a longer overall survival than those with low FLNA (p < 0.05). In conclusion, our data suggest that FLNA may represent a "protective" factor in ACCs, and the integration of FLNA immunohistochemical expression in ACC tissues along with other clinical and molecular markers could be helpful to improve diagnostic accuracy and prognosis prediction in ACCs.

A New Hybrid Sensitive PANI/SWCNT/Ferrocene-Based Layer for a Wearable CO Sensor.

Developing a sensing layer with high electroactive properties is an important aspect for proper functionality of a wearable sensor. The polymeric nanocomposite material obtained by a simple electropolymerization on gold interdigitated electrodes (IDEs) can be optimized to have suitable conductive properties to be used with direct current (DC) measurements. A new layer based on polyaniline:poly(4-styrenesulfonate) (PANI:PSS)/single-walled carbon nanotubes (SWCNT)/ferrocene (Fc) was electrosynthesized and deposed on interdigital transducers (IDT) and was characterized in detail using electrochemical impedance spectroscopy (EIS), cyclic voltammetry (CV), scanning electron microscopy (SEM), Raman spectroscopy, X-ray photoemission spectroscopy (XPS), and X-ray diffraction (XRD). The sensor characteristics of the material towards carbon monoxide (CO) in the concentration range of 10-300 ppm were examined, showing a minimal relative humidity interference of only 1% and an increase of sensitivity with the increase of CO concentration. Humidity interference could be controlled by the number of CV cycles when a compact layer was formed and the addition of Fc played an important role in the decrease of humidity. The results for CO detection can be substantially improved by optimizing the number of deposition cycles and enhancing the Fc concentration. The material was developed for selective detection of CO in real environmental conditions and shows good potential for use in a wearable sensor.

Combined Systematic and MRI-US Fusion Prostate Biopsy Has the Highest Grading Accuracy When Compared to Final Pathology.

Background and objectives: Systematic prostate biopsy (SB) has a low Gleason group (GG) accuracy when compared to final pathology. This may negatively impact the inclusion of patients into specific risk groups and treatment choice. The aim of our study was to assess the GG accuracy of magnetic resonance imaging-ultrasound (MRI-US) fusion prostate biopsy. Materials and Methods: Of a cohort of minimally invasive radical prostatectomy (RP), we selected all patients who were diagnosed with prostate cancer (PCa) via MRI-US fusion biopsy (n = 115). Results: Combined biopsy had the highest rate for GG concordance (61.7% vs. 60.4% for SB vs. 45.3% for MRI-US fusion biopsy) and the lowest for upgrading (20.9% vs. 24.5% for SB vs. 34.9% for MRI-US fusion biopsy), p < 0.0001. No clinical data were predictive for upgrading or downgrading at final pathology. Locally advanced PCa was associated with a high Prostate Imaging-Reporting and Data System (PIRADS) score (p = 0.0014) and higher percentages of positive biopsy cores (PBC)/targeted (p = 0.0002) and PBC/total (p = 0.01). Positive surgical margins were correlated with higher percentages of PBC/systematic (p = 0.003) and PBC/total (p = 0.009). Conclusions: Pre-biopsy prostate MRI improves GG concordance between biopsy and RP. Combined biopsy provides the highest grading accuracy when compared to final pathology. Targeted and systematic biopsy data are predictive for adverse pathologic outcomes.

Recovery of Adrenal Function after Pituitary Surgery in Patients with Cushing Disease: Persistent Remission or Recurrence?

BACKGROUND: Cushing disease (CD) represents the principal cause of endogenous hypercortisolism. The first-line therapy of CD is surgical removal of the ACTH-secreting pituitary adenoma, which is generally followed by adrenal insufficiency (AI). OBJECTIVE: To analyze the recovery of AI in patients with CD after pituitary surgery in relation with recurrence and persistent remission of CD. PATIENTS AND METHODS: We performed a retrospective analysis of patients with CD who met the following inclusion criteria: adult age, presence of AI 2 months after the surgical intervention, and a minimum follow-up of 3 years after the surgical intervention. RESULTS: Sixty-one patients were followed for a median of 6 years. Ten (16.4%) patients recurred during follow-up. The patients who restored adrenal function did so after a median time of 19 months, with a significantly shorter time in the recurrence group (12.5 vs. 25 months, p = 0.008). All 10 patients who recurred recovered their adrenal function within 22 months. The recovery rate of AI in the persistent remission group was 37.3% (19/51) at 3 years and 55.8% (24/43) at 5 years. In all patients the duration of AI was negatively associated with disease recurrence. CONCLUSION: The duration of postsurgical AI in patients with recurrent CD is significantly shorter than that in patients with persistently remitted CD, and this parameter may be a useful predictor of recurrence. Patients showing a normal pituitary-adrenal axis within 2 years after surgery should be strictly monitored as they are at higher risk of disease relapse.

AGEs-Induced IL-6 Synthesis Precedes RAGE Up-Regulation in HEK 293 Cells: An Alternative Inflammatory Mechanism?

Advanced glycation end products (AGEs) can activate the inflammatory pathways involved in diabetic nephropathy. Understanding these molecular pathways could contribute to therapeutic strategies for diabetes complications. We evaluated the modulation of inflammatory and oxidative markers, as well as the protective mechanisms employed by human embryonic kidney cells (HEK 293) upon exposure to 200 µg/mL bovine serum albumine (BSA) or AGEs-BSA for 12, 24 and 48 h. The mRNA and protein expression levels of AGEs receptor (RAGE) and heat shock proteins (HSPs) 27, 60 and 70, the activity of antioxidant enzymes and the expression levels of eight cytokines were analysed. Cell damage via oxidative mechanisms was evaluated by glutathione and malondialdehyde levels. The data revealed two different time scale responses. First, the up-regulation of interleukin-6 (IL-6), HSP 27 and high catalase activity were detected as early as 12 h after exposure to AGEs-BSA, while the second response, after 24 h, consisted of NF-κB p65, RAGE, HSP 70 and inflammatory cytokine up-regulation, glutathione depletion, malondialdehyde increase and the activation of antioxidant enzymes. IL-6 might be important in the early ignition of inflammatory responses, while the cellular redox imbalance, RAGE activation and NF-κB p65 increased expression further enhance inflammatory signals in HEK 293 cells.

Comprehensive and critical view on the anti-inflammatory and immunomodulatory role of natural phenolic antioxidants.

The immune response encompasses innate and adaptive immunity, each with distinct and specific activities. The innate immune system is constituted by phagocytic cells, macrophages, monocytes and neutrophils, the cascade system, and different classes of receptors such as toll-like receptors that are exploited by the innate immune cells. The adaptive immune system is antigen-specific, encompassing memory lymphocytes and the corresponding specific receptors. Inflammation is understood as an activation of different signaling pathways such as toll-like receptors or nuclear factor kappa-light-chain-enhancer of activated B cells, with an increase in nitric oxide, inflammatory cytokines and chemokines. Increased oxidative stress has been identified as main source of chronic inflammation. Phenolic antioxidants modulate the activities of lymphocytes and macrophages by impacting cytokines and nitric oxide release, exerting anti-inflammatory effect. The nuclear-factor kappa-light-chain-enhancer of activated B cells signaling pathway and the mitogen-activated protein kinase pathway are targeted, alongside an increase in nuclear factor erythroid 2-related factor mediated antioxidant response, triggering the activity of antioxidant enzymes. The inhibitive potential on phospholipase A2, cyclooxygenase and lipoxygenase in the arachidonic acid pathway, and the subsequent reduction in prostaglandin and leukotriene generation, reveals the potential of phenolics as inflammation antagonists. The immunomodulative potential encompasses the capacity to interfere with proinflammatory cytokine synthesis and with the expression of the corresponding genes. A diet rich in antioxidants can result in prevention of inflammation-related pathologies. More investigations are necessary to establish the role of these antioxidants in therapy. The appropriate delivery system and the prooxidant effects exhibited at large doses, or in the presence of heavy metal cations should be regarded.

Surgical patient registries: scoping study of challenges and solutions.

Patient surgical registries are essential tools for public health specialists, creating research opportunities through linkage of registry data with healthcare outcomes. However, little is known regarding data error sources in the management of surgical registries. In June 2022, we undertook a scoping study of the empirical literature including publications selected from the PUBMED and EMBASE databases. We selected 48 studies focussing on shared experiences centred around developing surgical patient registries. We identified seven types of data specific challenges, grouped in three categories- data capture, data analysis and result dissemination. Most studies underlined the risk for a high volume of missing data, non-uniform geographic representation, inclusion biases, inappropriate coding, as well as variations in analysis reporting and limitations related to the statistical analysis. Finally, to expand data usability, we discussed cost-effective ways of addressing these limitations, by citing aspects from the protocols followed by established exemplary registries.

Interplay of Oxidative Stress, Inflammation, and Autophagy in RAW 264.7 Murine Macrophage Cell Line Challenged with Si/SiO2 Quantum Dots.

Quantum dots (QDs) with photostable fluorescence are recommended for imaging applications; however, their effect on living cells is incompletely understood. We aimed to elucidate the RAW 264.7 murine macrophage cell line's response to the Si/SiO2 QDs challenge. Cells were exposed to 5 and 15 µg/mL Si/SiO2 QDs for 6 h, 12 h, and 24 h. Cell metabolic activity and viability were assessed by MTT, live/dead, and dye-exclusion assays. Oxidative stress and membrane integrity were assessed by anion superoxide, malondialdehyde, and lactate dehydrogenase activity evaluations. Antioxidative enzyme activities were analyzed by kinetic spectrophotometric methods. Cytokines were analyzed with an antibody-based magnetic bead assay, PGE2 was assessed by ELISA, and Nrf-2, Bcl-2, Beclin 1, and the HSPs were analyzed by western blot. Autophagy levels were highlighted by fluorescence microscopy. The average IC50 dose for 6, 12, and 24 h was 16.1 ± 0.7 µg/mL. Although glutathione S-transferase and catalase were still upregulated after 24 h, superoxide dismutase was inhibited, which together allowed the gradual increase of malondialdehyde, anion superoxide, nitric oxide, and the loss of membrane integrity. G-CSF, IL-6, TNF-α, MIP-1ß, MCP-1, Nrf-2, PGE2, and RANTES levels, as well as autophagy processes, were increased at all time intervals, as opposed to caspase 1 activity, COX-2, HSP60, and HSP70, which were only upregulated at the 6-h exposure interval. These results underscore that Si/SiO2 QDs possess significant immunotoxic effects on the RAW 264.7 macrophage cell line and stress the importance of developing effective strategies to mitigate their adverse impact.

Case Report: Opposite Tumoral and Hormonal Responses to Low-dose Pasireotide in Cushing's Disease.

BACKGROUND: Pasireotide is a multireceptor somatostatin analogue approved for the treatment of patients with Cushing's disease (CD) who are ineligible or poor candidates for pituitary surgery. Here we present a patient with severe recurrent CD who was treated with pasiretide and showed opposite results between hormonal levels and pituitary tumour size. CASE PRESENTATION: A 54-year-old woman was diagnosed with CD, a first surgical transsphenoidal procedure was performed at the time of diagnosis, and the disease recurred seven years later. She underwent a second transsphenoidal surgery, but despite apparent complete removal of the adenoma, the hypercortisolism worsened. Magnetic resonance imaging showed a tiny remnant of the adenoma adjacent to the cavernous sinus, and ketoconazole was started at a dose of 800 mg/day. Due to the persistence of pathological urinary free cortisol levels, 600 µg bid pasireotide was added. The combination therapy induced first normalisation of urinary free cortisol and later hypoadrenalism, so that ketoconazole was discontinued and pasireotide was maintained. A marked clinical improvement was achieved with pasireotide. Adrenal insufficiency persisted despite progressive tapering of the pasireotide dose to 150 mg once daily. Pituitary magnetic resonance imaging performed at 12 and 24 months during low-dose pasireotide treatment showed a few millimetres increase of the remnant. CONCLUSIONS: This report suggests that CD Pas induces an opposite effect between hormonal profile and increase of pituitary tumor size. This peculiar phenomenon may be a consequence of the unusually low doses of pasireotide needed to control hormonal hypersecretion.

Predicting Pregnancy Outcome in Dairy Cows: The Role of IGF-1 and Progesterone.

The purpose of this study was to determine the link between insulin-like growth factor 1 (IGF-1), progesterone (PROG), non-esterified fatty acids (NEFAs), ß-hydroxybutyrate (BHB), and glucose (GLU) and pregnancy probability after the first artificial insemination (AI) and during the first 100 days in milk (DIM), during the critical transition period. We determined levels of serum IGF-1, PROG, NEFA, BHB, and GLU in Holstein dairy cows via ELISA, using blood samples collected 7 days before parturition (DAP) until 21 days postparturition (DPP). The group was split into cows diagnosed pregnant at 100 DIM (PREG) and those that did not conceive at 100 and 150 DIM (NPREG). Serum IGF-1 and PROG median levels at 7 DAP were significantly higher in PREG vs. NPREG (p = 0.029), the only statistically significant differences across the subgroups. At 7 DAP, IGF-1 levels within the initial group showed a strong negative correlation with PROG (r = -0.693; p = 0.006), while for the PREG subgroup, the IGF-1 levels exhibited a very strong positive correlation with GLU (r = 0.860; p = 0.011) and NEFA (r = 0.872; p = 0.013). IGF-1 and PROG levels detected at 7 DAP may be useful to predict pregnancy at 100 DIM. The positive correlation of NEFA and GLU levels during the transition period demonstrates that the initial group is not in NEB; thus, the NEFA level was not a decisive factor for reproduction success.

Structural and oxidative changes in the kidney of crucian carp induced by silicon-based quantum dots.

Silicon-based quantum dots were intraperitoneally injected in Carassius auratus gibelio specimens and, over one week, the effects on renal tissue were investigated by following their distribution and histological effects, as well as antioxidative system modifications. After three and seven days, detached epithelial cells from the basal lamina, dilated tubules and debris in the lumen of tubules were observed. At day 7, nephrogenesis was noticed. The reduced glutathione (GSH) concentration decreased in the first three days and started to rise later on. The superoxide dismutase (SOD) activity increased only after one week, whereas catalase (CAT) was up-regulated in a time-dependent manner. The activities of glutathione reductase (GR) and glutathione peroxidise (GPX) decreased dramatically by approximately 50% compared to control, whereas the glutathione-S-transferase (GST) and glucose-6-phosphate dehydrogenase (G6PDH) increased significantly after 3 and 7 days of treatment. Oxidative modifications of proteins and the time-dependent increase of Hsp70 expression were also registered. Our data suggest that silicon-based quantum dots induced oxidative stress followed by structural damages. However, renal tissue is capable of restoring its integrity by nephron development.

Impact of silicon-based quantum dots on the antioxidative system in white muscle of Carassius auratus gibelio.

Silicon-based quantum dots were intraperitoneally injected in individuals of Carassius auratus gibelio. Their effects on white muscle were investigated by following their distribution and impact on the antioxidative system. The GSH level significantly increased after 1 and 3 days of exposure by, respectively, 85.3 and 25.4%. Seven days later, GSH levels were similar to control concentrations. MDA concentration rose after three days by 46.9% and remained at the same level after 7 days. Protein thiol levels significantly decreased by 6.7 and 8.1% after 3 and 7 days, whereas advanced oxidation protein products increased by 12.7, respectively, 28.1% in the same time intervals. The protein reactive carbonyl groups were raised only after the first day of exposure and returned to the control level later on. SOD specific activity increased up to 48% after 7 days, while CAT activity increased by 328, 176, and 26% after 1, 3, and 7 days of treatment. GST specific activity was up-regulated by 87, 18, and 9%, while GR activity increased by 68, 34, and 9%. G6PD activity was up-regulated by 12, 22, and 50%, whereas GPx activity raised by 75 and 109% compared to control after, respectively, 1, 3, and 7 days. Our results suggest that oxidative stress induced by silicon-based quantum dots was not strong enough to cause permanent damage in the white muscle of crucian carp.

Antitumoral activity of 1,2,4-oxadiazoles compounds isolated from the Neowerdermannia vorwerkii in liver and colon human cancer cells.

Two unknown 1,2,4-oxadiazoles (3-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,4-oxadiazole and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole) and one known 1,2,4-oxadiazole (5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole) were isolated from tubers of Neowerdermannia vorwerkii, collected from the San Juan Huancollo, Ingavi province, La Paz, Bolivia. The chemical structures of these compounds were elucidated through NMR and HRMS spectroscopic analyses. All compounds showed apoptotic capacity against the SK-HEP-1 and Caco-2 tumour cells. 5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2, 4-oxadiazole showed slight apoptotic capacities, with an IC50 between 17.46 ± 0.75 to 15.91 ± 0.62 µM and 39.29 ± 0.98 to 34.81 ± 0.70 µM, respectively. 3-(pyridin-3-yl)-5-(thiophen-3-yl)-1,2,4-oxadiazole showed a higher apoptotic capacity with an IC50 in the range of 0.98 ± 0.11 to 0.76 ± 0.03 µM, similar to that of the positive control (Dimethylenastron).

Anti-inflammatory properties of Neowerdermannia vorwerkii Fric 'Achacana' used in treating stomach-related ailments.

ETHNO-PHARMACOLOGICAL RELEVANCE: The tuber of Neowerdermannia vorwerkii commonly known as 'Achacana' is used as an infusion in Andean countries to treat various gastrointestinal ailments, kidney and liver diseases. AIM OF THE STUDY: This study determined the anti-inflammatory activity of the aqueous extract from Neowerdermannia vorwerkii and identified the compounds related to this activity. MATERIALS AND METHODS: A bio-guided isolation of the active compounds of Neowerdermannia vorwerkii was carried out, selecting the sub-extracts and fractions depending on their anti-inflammatory activity in the Hs 738.St/Int, Hs 746T and NCI-N87 cells. RESULTS: Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are (3-(pyridin-3-yl)-5-(tiophen-3-yl)-1,2,4-oxadiazole (1), 5-(3-methoxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole (2) and 5-(3-hydroxyphenyl)-3-(pyridin-3-yl)-1,2,4-oxadiazole (3). Regarding their anti-inflammatory activity, the three compounds inhibited the production of cytokines (IL-1ß, IL-6 and TNF-α), however, compound 1 was the most active, with an IC50 of 0.87 µM in all cell lines. CONCLUSION: In the present study, the anti-inflammatory activity of the aqueous extract of Neowerdermannia vorwerkii was tested and analysed, following the isolation of three 1,2,4-oxadiazoles type compounds with similar pharmacological properties.

Wound healing, anti-inflammatory and anti-melanogenic activities of ursane-type triterpenes from Semialarium mexicanum (Miers) Mennega.

ETHNO-PHARMACOLOGICAL RELEVANCE: The bark of Semialarium mexicanum commonly known as 'Cancerina' is used as an infusion in Central America and Mexico to treat various wound infections, as well as skin and vaginal ulcers. AIM OF THE STUDY: This study aimed to determine the wound healing, anti-inflammatory and anti-melanogenic activities of the aqueous extract of Semialarium mexicanum and to identify the compounds related to these activities. MATERIALS AND METHODS: A bio-guided isolation of the active compounds of Semialarium mexicanum was carried out, selecting the sub-extracts and fractions depending on their wound healing, anti-inflammatory and anti-melanogenic activities in the RAW 264.7, NIH/3T3 and B16-F10 cells. RESULTS: Three compounds were obtained and characterised by nuclear magnetic resonance and mass spectrometry. These compounds are (3ß)-3-Hydroxy-urs-12-en-28-oic acid (1), (3ß)-Urs-12-ene-3,28-diol (2) and (2α, 19α)-2,19-Dihydroxy-3-oxo-urs-12-en-28-oic acid (3). Regarding the anti-inflammatory activity, the three compounds inhibited the production of NF-κB and NO, however, compound 3 was the most active with IC50 values of 8.15-8.19 µM and 8.94-9.14 µM, respectively, in all cell lines. The anti-melanogenic activity of these compounds was evaluated by the inhibition of tyrosinase and melanin in the B16-F10 cell line. The three compounds showed anti-melanogenic activity, however, compound 3 was the most active with an IC50 of 8.03 µM for the inhibition of tyrosinase production, and an IC50 of 8.53 µM for the inhibition of melanin production. Finally, concerning the wound healing activity, the three compounds presented proliferative activity in all the tested cell lines, however, compound 3 showed higher cell proliferation percentages than compounds 1 and 2 (88.89-89.60% compared to 64.92-65.71% and 71.53-71.99%, respectively). CONCLUSION: The wound healing, anti-inflammatory and anti-melanogenic activity of the aqueous extract of Semialarium mexicanum was tested and analysed in the present study, after having isolated three ursane-type triterpenes.

Multivariate Risk Analysis of RAS, BRAF and EGFR Mutations Allelic Frequency and Coexistence as Colorectal Cancer Predictive Biomarkers.

BACKGROUND: Biomarker profiles should represent a coherent description of the colorectal cancer (CRC) stage and its predicted evolution. METHODS: Using droplet digital PCR, we detected the allelic frequencies (AF) of KRAS, NRAS, BRAF, and EGFR mutations from 60 tumors. We employed a pair-wise association approach to estimate the risk involving AF mutations as outcome variables for clinical data and as predicting variables for tumor-staging. We evaluated correlations between mutations of AFs and also between the mutations and histopathology features (tumor staging, inflammation, differentiation, and invasiveness). RESULTS: KRAS G12/G13 mutations were present in all patients. KRAS Q61 was significantly associated with poor differentiation, high desmoplastic reaction, invasiveness (ypT4), and metastasis (ypM1). NRAS and BRAF were associated with the right-side localization of tumors. Diabetic patients had a higher risk to exhibit NRAS G12/G13 mutations. BRAF and NRAS G12/G13 mutations co-existed in tumors with invasiveness limited to the submucosa. CONCLUSIONS: The associations we found and the mutational AF we reported may help to understand disease processes and may be considered as potential CCR biomarker candidates. In addition, we propose representative mutation panels associated with specific clinical and histopathological features of CRC, as a unique opportunity to refine the degree of personalization of CRC treatment.

Antioxidant, anti-inflammatory and immunomodulatory roles of vitamins in COVID-19 therapy.

oxidative stress is caused by an abundant generation of reactive oxygen species, associated to a diminished capacity of the endogenous systems of the organism to counteract them. Activation of pro-oxidative pathways and boosting of inflammatory cytokines are always encountered in viral infections, including SARS-CoV-2. So, the importance of counteracting cytokine storm in COVID-19 pathology is highly important, to hamper the immunogenic damage of the endothelium and alveolar membranes. Antioxidants prevent oxidative processes, by impeding radical species generation. It has been proved that vitamin intake lowers oxidative stress markers, alleviates cytokine storm and has a potential role in reducing disease severity, by lowering pro-inflammatory cytokines, hampering hyperinflammation and organ failure. For the approached compounds, direct antiviral roles are also discussed in this review, as these activities encompass secretion of antiviral peptides, modulation of angiotensin-converting enzyme 2 receptor expression and interaction with spike protein, inactivation of furin protease, or inhibition of pathogen replication by nucleic acid impairment induction. Vitamin administration results in beneficial effects. Nevertheless, timing, dosage and mutual influences of these micronutrients should be carefullly regarded.