Levels of different subtypes of tumour-infiltrating lymphocytes correlate with each other, with matched circulating lymphocytes, and with survival in breast cancer

Purpose: Breast cancer tumour-infiltrating lymphocytes associate with clinico-pathological factors, including survival, although the literature includes many conflicting findings. Our aim was to assess these associations for key lymphocyte subtypes and in different tumour compartments, to determine whether these provide differential correlations and could, therefore, explain published inconsistencies. Uniquely, we also examine whether infiltrating levels merely reflect systemic lymphocyte levels or whether local factors are predominant in recruitment. Methods: Immunohistochemistry was used to detect tumour-infiltrating CD20+ (B), CD4+ (helper T), CD8+ (cytotoxic T) and FoxP3+ (regulatory T) cells in breast cancers from 62 patients, with quantification in tumour stroma, tumour cell nests, and tumour margins. Levels were analysed with respect to clinico-pathological characteristics and matched circulating levels (determined by flow-cytometry). Results: CD4+ lymphocytes were the most prevalent subtype in tumour stroma and at tumour edge and CD8+ lymphocytes were most prevalent in tumour nests; FoxP3+ lymphocytes were rarest in all compartments. High grade or hormone receptor negative tumours generally had significantly increased lymphocytes, especially in tumour stroma. Only intra-tumoural levels of CD8+ lymphocytes correlated significantly with matched circulating levels (p < 0.03), suggesting that recruitment is mainly unrelated to systemic activity. High levels of stromal CD4+ and CD20+ cells associated with improved survival in hormone receptor negative cases (p < 0.04), while tumour nest CD8+ and FoxP3+ cells associated with poor survival in hormone receptor positives (p < 0.005). Conclusions: Lymphocyte subtype and location define differential impacts on tumour biology, therefore, roles of tumour-infiltrating lymphocytes will only be unravelled through thorough analyses that take this into account

Shared Situational Awareness within the Hospital Emergency Context: A Scoping Review

Background. Shared Situation Awareness (SSA) has been applied in many fields such as sport, the military and aviation with promising outcomes on team performance. The application of SSA within the hospital emergency healthcare context has not been explored yet. The aim of this scoping review is to explore and map literature related to shared situational awareness within the hospital emergency healthcare context. Methods. The Arksey and O&rsquo;Malley (2005) framework was used in which three electronic databases were searched for evidence investigating SSA within a hospital emergency healthcare context. Results. A review of the literature showed a clear lack of evidence that directly investigates SSA within the context of hospital emergency care. In the emergency medical field, the term SSA is seldom used and &lsquo;team situation awareness&rsquo; is the most frequently used term. The most common framework was the three-level framework. Two techniques were reported in the selected studies to investigate SSA (1) freeze probe technique and (2) observer-based rating technique. The freeze probe technique mandates a simulation or artificial environment, while the observer-based rating technique could be applied in an ecological as well as an artificial environment. There is no standardized technique to calculate the score of the SSA. Finally, there was a significant impact of SSA on clinical team performance as well as some related skills such as leadership, task management, mindfulness and task prioritization. Conclusions. Reviewing the literature revealed a lack of studies investigating the use of SSA within the context of hospital emergency care. There is also a lack of agreement on how a SSA score should be calculated. Further studies are required to overcome these issues

Non-Linear Analysis of Novel Equivalent Circuits of Single-Diode Solar Cell Models with Voltage-Dependent Resistance

The most commonly used model of solar cells is the single-diode model, with five unknown parameters. First, this paper proposes three variants of the single-diode model, which imply the voltage dependence of the series resistance, parallel resistance, and both resistors. Second, analytical relationships between the current and the voltage expressed were derived using the Lambert W function for each proposed model. Third, the paper presents a hybrid algorithm, Chaotic Snake Optimization (Chaotic SO), combining chaotic sequences with the snake optimization algorithm. The application of the proposed models and algorithm was justified on two well-known solar photovoltaic (PV) cells—RTC France solar cell and Photowatt-PWP201 module. The results showed that the root-mean-square-error (RMSE) values calculated by applying the proposed equivalent circuit with voltage dependence of both resistors are reduced by 20% for the RTC France solar cell and 40% for the Photowatt-PWP201 module compared to the standard single-diode equivalent circuit. Finally, an experimental investigation was conducted into the applicability of the proposed models to a solar laboratory module, and the results obtained proved the relevance and effectiveness of the proposed models

Computational intelligence modeling using Artificial Intelligence and optimization of processing of small-molecule API solubility in supercritical solvent

Preparation of small-molecule API (Active Pharmaceutical Ingredient) at submicron size would be of great benefit for pharmaceutical engineering, as the drug particles at submicron size possess higher solubility in water. Indeed, the drug bioavailability can be enhanced when the nanomedicine is prepared. In this study, the solubility of the drug desoxycorticosterone acetate (DA) is being examined to assess its viability of nanonization using supercritical operation. Two inputs are temperature and pressure which were considered for machine learning modeling in this study. The drug's solubility is the only output to be estimated by the optimized models. This dataset has 45 rows of data that were gathered at 5 different pressure and temperature levels. Support vector machine (SVM) is used as the core of the models built in this research. Epsilon-SVR and nu-SVR are models based on this concept, which together with two different polynomial and RBF kernels form the four models built in this research for estimation of DA drug solubility. The models are also optimized with the help of a new TLCO method. All four final models have an R2 score higher than 0.9, and among them, the Epsilon-SVR model with RBF kernel has the best performance with 0.967

Synthesis and characterization of ZnO–TiO2–chitosan–escin metallic nanocomposites: Evaluation of their antimicrobial and anticancer activities

This work intended to formulate bio-nanocomposites of zinc oxide (ZnO), titanium oxide (TiO2), chitosan, and escin, characterize their physical properties, and evaluate their antimicrobial and anticancer properties. X-ray diffractometers (XRD) and scanning and transmission electron microscopes were applied to characterize the morphology and ultrastructure of chemically synthesized bio-nanocomposites. To investigate the functional groups of bio-nanocomposites, we used Perkin–Elmer spectrometers for Fourier transform infrared (FTIR) analysis and photoluminescence (PL) spectroscopy for PL spectrum analysis. Antimicrobial activities against bacterial and fungal strains were tested with agar well diffusion. Bio-nanocomposites were tested for anticancer effects on a MOLT4 blood cancer cell line using morphological analysis, methyl thiazole tetrazolium assay, apoptosis by acridine orange/ethidium bromide, and mitochondrial membrane potential (ΔΨm). In XRD, FTIR, and PL, the active compounds of ZnO–TiO2, chitosan, and escin peaks were observed. Our bio-nanocomposites demonstrated antimicrobial activity against bacterial and fungal pathogens. The bio-nanocomposite was cytotoxic to MOLT4 cells at an IC50 concentration of 33.4 µg·mL−1. Bio-nanocomposites caused cytotoxicity, changes in cell morphology, and mitochondrial membrane potential degradation, all of which resulted in apoptotic cell death. MOLT4 cells were found to be responsive to bio-nanocomposites based on ZnO–TiO2–chitosan–escin

Effects of Albumin–Chlorogenic Acid Nanoparticles on Apoptosis and PI3K/Akt/mTOR Pathway Inhibitory Activity in MDA-MB-435s Cells

In this study, we synthesized, characterized, and explored the anti-microbial and anti-cancer effects of albumin–chlorogenic acid nanoparticles (NPs). Characterization studies with a UV-vis spectrophotometer, FTIR, PL spectrum, TEM, FESEM, XRD, and DLA analysis showed patterns confirming the physio–chemical nature of biogenic nanocomposites. Further, anti-microbial studies using bacterial strains Staphylococcus aureus, Streptococcus pneumonia, Bacillus subtilis, Escherichia coli, Pseudomonas aeruginosa, Vibrio cholera, and fungal strain Candida albicans showed significant (p < 0.05) anti-bacterial and anti-fungal activities. Next, we used MDA-MB-435s, a human cell line, to evaluate the anti-cancer effects of albumin–chlorogenic acid NPs. Cytotoxic studies revealed its IC50 concentration at 24 μg/mL after a 24 h treatment of MDA-MB-435s cells. We chose this IC50 dose to analyze albumin–chlorogenic acid NPs anti-cancer effects in vitro. MDA-MB-435s cells exposed to our NPs were studied via AO/EtBr staining, cell cycle analyses via PI staining, the status of whole genomic damage via comet assay, levels of apoptotic cells via annexin V/PI staining, ROS generation via DCFH-DA staining, an assay of antioxidant enzymes catalase, superoxide dismutase, and antioxidant GSH, via ELISA analyses of apoptotic markers caspase-3, 8, 9, Bax, Bcl-2, CytC, and p53, PI3/AKT/mTOR pathway. Our results collectively showed albumin–chlorogenic acid NPs induced apoptosis via p53-dependent and PI3/AKT/mTOR inhibition in MDA-MB-435s cells. Our results denote albumin–chlorogenic acid NPs can be used as an effective candidate for anti-microbial and anti-cancer applications; however, further in vivo confirmatory studies are warranted

Therapeutic Potential of Albumin Nanoparticles Encapsulated Visnagin in MDA-MB-468 Triple-Negative Breast Cancer Cells

Breast cancer is among the most recurrent malignancies, and its prevalence is rising. With only a few treatment options available, there is an immediate need to search for better alternatives. In this regard, nanotechnology has been applied to develop potential chemotherapeutic techniques, particularly for cancer therapy. Specifically, albumin-based nanoparticles are a developing platform for the administration of diverse chemotherapy drugs owing to their biocompatibility and non-toxicity. Visnagin, a naturally derived furanochromone, treats cancers, epilepsy, angina, coughs, and inflammatory illnesses. In the current study, the synthesis and characterization of albumin visnagin (AV) nanoparticles (NPs) using a variety of techniques such as transmission electron microscopy, UV-visible, Fourier transform infrared, energy dispersive X-ray composition analysis, field emission scanning electron microscopy, photoluminescence, X-Ray diffraction, and dynamic light scattering analyses have been carried out. The MTT test, dual AO/EB, DCFH-DA, Annexin-V-FITC/PI, Propidium iodide staining techniques as well as analysis of apoptotic proteins, antioxidant enzymes, and PI3K/Akt/mTOR signaling analysis was performed to examine the NPs’ efficacy to suppress MDA-MB-468 cell lines. The NPs decreased cell viability increased the amount of ROS in the cells, disrupted membrane integrity, decreased the level of antioxidant enzymes, induced cell cycle arrest, and activated the PI3K/Akt/mTOR signaling cascade, ultimately leading to cell death. Thus, AV NPs possesses huge potential to be employed as a strong anticancer therapy alternative

In vitro anti-cancer and antimicrobial effects of manganese oxide nanoparticles synthesized using the Glycyrrhiza uralensis leaf extract on breast cancer cell lines

In this study, we evaluated the antiproliferative and apoptotic properties of Pluronic-F127-containing manganese oxide nanoparticles (PF-127-coated Mn2O3 NPs) derived from the leaf extract of Glycyrrhiza uralensis (GU) on breast adenocarcinoma, MCF7, and MDA-MB-231 cell lines. The leaf extract of GU contains bioactive molecules that act as a reducing or capping agent to form Mn2O3 NPs. Various analytical techniques were used to characterize the physiochemical properties of PF-127-coated Mn2O3 NPs, including spectroscopy (ultralight-Vis, Fourier transform infrared, photoluminescence), electron microscopy (field emission scanning electron microscopy and transmission electron microscopy), X-ray diffraction (XRD), electron diffracted X-ray spectroscopy (EDAX), and dynamic light scattering. The average crystallite size of Mn2O3 NPs was estimated to be 80 nm, and the NPs had a cubic crystalline structure. PF127-encapsulated Mn2O3 NPs significantly reduce MDA-MB-231 and MCF-7 cell proliferation, while increasing endogenous ROS and lowering mitochondrial matrix protein levels. DAPI, EtBr/AO dual staining, and Annexin-V-FITC-based flow cytometry analysis revealed that PF127-coated Mn2O3 NP-treated breast cancer cells exhibit nuclear damage and apoptotic cell death, resulting in cell cycle arrest in the S phase. Furthermore, PF127-encapsulated Mn2O3 NPs show strong antimicrobial efficacy against various strains. As a result, we can conclude that PF127-coated Mn2O3 NPs may be effective as future anticancer agents and treatment options for breast cancer

Synthesis, Characterization, and Antimicrobial and Antiproliferative Effects of CuO-TiO2-Chitosan-Escin Nanocomposites on Human Leukemic MOLT4 Cells

Nanocomposites comprised of CuO-TiO2-chitosan-escin, which has adjustable physicochemical properties, provide a solution for therapeutic selectivity in cancer treatment. By controlling the intrinsic signaling primarily through the mitochondrial signaling pathway, we desired nanocomposites with enhanced anticancer activity by containing CuO-TiO2-chitosan-escin. The metal oxides CuO and TiO2, the natural polymer chitosan, and a phytochemical compound escin were combined to form CuO-TiO2-chitosan-escin nanocomposites. The synthesized nanocomposites were confirmed and characterized using FTIR spectroscopy, TEM, and UV-Vis absorption spectroscopy. A human leukemia cell line (MOLT-4) was used to assess the efficacy and selectivity of nanocomposites. Based on a cytotoxicity study, CuO-TiO2-chitosan-escin nanocomposites had inhibition concentrations (IC50) of 13.68, 8.9, and 7.14 &micro;g/mL against human T lymphoblast cells after 24, 48, and 72 h of incubation, respectively. Compared with untreated MOLT-4 cells, CuO-TiO2-chitosan-escin nanocomposite-treated cells significantly increased (p &lt; 0.05) caspase-3, -8, and -9 and decreased the levels of antioxidant enzymes GR, SOD, and GSH. Furthermore, MDA for lipid peroxidase and ROS levels significantly increased (p &lt; 0.05) in the treated cells than in the untreated cells. Remarkably, CuO-TiO2-chitosan-escin nanocomposite-mediated control of cell cycles were mainly achieved through the activation of caspase-3, -8, and -9

Overexpression of the cancer stem cell marker CD133 confers a poor prognosis in invasive breast cancer

PurposeCD133/ prominin 1 is a cancer stem cell marker associated with cancer progression and patient outcome in a variety of solid tumours, but its role in invasive breast cancer (BC) remains obscure. The current study aims to assess the prognostic value of CD133 expression in early invasive BC.MethodsCD133 mRNA was assessed in the METABRIC cohort and at the proteomic level using immunohistochemistry utilising a large well-characterised BC cohort. Association with clinicopathological characteristics, expression of other stem cell markers and patient outcome were evaluated.ResultsHigh expression of CD133 either in mRNA or protein levels was associated with characteristics of poor prognosis including high tumour grade, larger tumour size, high Nottingham Prognostic Index, HER2 positivity and hormonal receptor negativity (all; p less than 0.01). Tumours expressing CD133 showed higher expression of other stem cell markers including CD24, CD44, SOX10, ALDHA3 and ITGA6. High expression of CD133 protein was associated with shorter BC-specific survival (p = 0.026). Multivariate analysis revealed that CD133 protein expression was an independent risk factor for shorter BC-specific survival (p = 0.038).ConclusionThis study provides evidence for the prognostic value of CD133 in invasive BC. A strong positive association of BC stem cell markers is observed at the protein level. Further studies to assess the value of stem cell markers individually or in combination in BC is warranted