Search Results (1,714)

The rapid growth and high nutrient density in modern broiler production have led to issues like woody breast myopathy (WBM), footpad dermatitis, and fat accumulation, affecting welfare and profitability. This study evaluated the effects of amino acid (AA) and apparent metabolizable energy (AME) reductions on organ development, carcass yield, WBM incidence, and economic returns in Cobb 700 and Ross 708 broilers. Two trials were conducted, one per strain, using a factorial design with 12 treatments (four AA × three AME). Each trial included 864 broilers, randomly assigned to six replicate blocks, with 12 pens per block (six males and six females per pen). Diets contained 70%, 80%, 90%, or 100% of digestible AA and 84%, 92%, or 100% AME based on breeder recommendations. A 30% AA reduction increased fat pad weight, promoted proventriculus and jejunum development (day 58), reduced carcass and tenderloin weights, lowered moderate/severe WBM incidence (day 47), and shortened footpad dermatitis. A 16% AME reduction decreased fat pad weight, improved muscle production and returns, but reduced normal breast percentage (days 40 and 47). The recommended protein–energy ratio (g/MJ) for optimal economic returns was as follows: 19.78 (0–10 d), 17.51 (11–24 d), 16.03 (25–39 d), and 15.25 (40–63 d). Full article

The early detection of cancerous lesions is a challenging task given the cancer biology and the variability in tissue characteristics, thus rendering medical image analysis tedious and time-inefficient. In the past, conventional computer-aided diagnosis (CAD) and detection methods have heavily relied on the visual inspection of medical images, which is ineffective, particularly for large and visible cancerous lesions in such images. Additionally, conventional methods face challenges in analyzing objects in large images due to overlapping/intersecting objects and the inability to resolve their image boundaries/edges. Nevertheless, the early detection of breast cancer lesions is a key determinant for diagnosis and treatment. In this study, we present a deep learning-based technique for breast cancer lesion detection, namely blob detection, which automatically detects hidden and inaccessible cancerous lesions in unsupervised human breast histology images. Initially, this approach prepares and pre-processes data through various augmentation methods to increase the dataset size. Secondly, a stain normalization technique is applied to the augmented images to separate nucleus features from tissue structures. Thirdly, morphology operation techniques, namely erosion, dilation, opening, and a distance transform, are used to enhance the images by highlighting foreground and background pixels while removing overlapping regions from the highlighted nucleus objects in the image. Subsequently, image segmentation is handled via the connected components method, which groups highlighted pixel components with similar intensity values and assigns them to their relevant labeled components (binary masks). These binary masks are then used in the active contours method for further segmentation by highlighting the boundaries/edges of ROIs. Finally, a deep learning recurrent neural network (RNN) model automatically detects and extracts cancerous lesions and their edges from the histology images via the blob detection method. This proposed approach utilizes the capabilities of both the connected components method and the active contours method to resolve the limitations of blob detection. This detection method is evaluated on 27,249 unsupervised, augmented human breast cancer histology dataset images, and it shows a significant evaluation result in the form of a $98.82\%$ F1 accuracy score. Full article

Doxorubicin (DOX), an anthracycline chemotherapeutic agent, demonstrates efficacy against various types of cancer. Combining DOX with the antihypertensive drug hydralazine (HDZ) has been proposed as cardioprotective combination therapy, allowing for the use of a reduced DOX dose. The current study describes the remote co-loading of DOX and HDZ into PEGylated liposomes using, for the first time, a simultaneous pH gradient technique. First, PEGylated liposomes were prepared using an ethanol injection method and remotely loaded with DOX and HDZ. Then, DOX- and HDZ-loaded liposomes (Lip-DOX-HDZ) were characterized using DLS, TEM, FTIR, thermal analysis, drug leakage, and stability. Furthermore, the cellular uptake and cytotoxicity were evaluated in two human breast cancer cell lines (MCF7 and MDA-MB-231) and two normal cell lines (human dermal fibroblasts (HDFs) and rat cardiac cells (H9C2)). The results revealed that Lip-DOX-HDZ had a particle size of 158 ± 18 nm, PDI of 0.22 ± 0.08, and zeta potential of −22 ± 5 mV. The encapsulation efficiency of DOX and HDZ was 90% and 30%, respectively. Moreover, the IC₅₀ values of Lip-DOX-HDZ showed higher cytotoxicity against the MDA-MB-231 (5.5 ± 0.4 µM) and MCF7 (6.25 ± 0.9 µM) breast cancer cell lines compared to normal cells: HDF cells (20 ± 3.0 µM) and H9C2 cardiac cells (19.37 ± 2.0 µM). Our study found that remotely loaded Lip-DOX-HDZ showed a ~4-fold lower toxicity and selectivity for normal cells (HDFs and H9C2), compared to breast cancer cells. This suggests that Lip-DOX-HDZ is a promising nanocarrier for both DOX and HDZ, clinically potent molecules. Full article

Background: Telomeres and cellular senescence are critical biological processes implicated in cancer development and progression, including breast cancer, through their influence on genomic stability and modulation of the tumor microenvironment. Methods: This study integrated bulk RNA sequencing and single-cell RNA sequencing (scRNA-seq) data to establish a gene signature associated with telomere maintenance and cellular senescence for prognostic prediction in breast cancer. Telomere-related genes (TEGs) and senescence-associated genes were curated from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. A comprehensive machine learning framework incorporating 101 algorithmic combinations across 10 survival modeling approaches, including random survival forests and ridge regression, was employed to develop a robust prognostic model. Results: A set of 19 key telomere- and senescence-related genes was identified as the optimal prognostic signature. The model demonstrated strong predictive accuracy and was successfully validated in multiple independent cohorts. Functional enrichment analyses indicated significant associations with immune responses and aging-related pathways. Single-cell transcriptomic analysis revealed marked cellular heterogeneity, identifying distinct subpopulations (fibroblasts and immune cells) with divergent risk scores and biological pathway activity. Additionally, pseudo-time trajectory analysis and intercellular communication mapping provided insights into the dynamic evolution of the tumor microenvironment. Immunohistochemical (IHC) validation using data from the Human Protein Atlas confirmed differential protein expression between normal and tumor tissues for several of the selected genes, reinforcing their biological relevance and clinical utility. Conclusions: This study presents a novel 19-gene telomere- and senescence-associated signature with strong prognostic value in breast cancer. These findings enhance our understanding of tumor heterogeneity and may inform precision oncology approaches and future therapeutic strategies. Full article

Background/Objectives: The UbcH10 protein plays an important role in a variety of human malignancies, including thyroid, breast, ovarian, and colorectal carcinomas. It has been previously reported that UbcH10 is overexpressed in non-small cell lung cancer (NSCLC) compared to normal lungs and that its expression is directly and inversely correlated with the mutational status of p53 and EGFR, respectively. Methods: We transfected lung cancer cells with wild-type and mutant forms of EGFR, modulated the expression of UbcH10 and p53, and treated these cells with tyrosine kinase inhibitor (TKI) erlotinib. Using Western blotting, we evaluated the expression of UbcH10 induced by EGFR and p53. Finally, we employed immunohistochemistry to assess the levels of UbcH10 expression in a subset of NSCLC patients receiving TKI therapy. Results: We reported a possible modulation of UbcH10 expression by the overexpression of wild-type and mutant EGFR in H460 lung cancer cells, potentially through p53. The enforced expression of UbcH10 in cells transfected with mutant EGFR suggested a potential increase in resistance to erlotinib treatment. Finally, immunohistochemical analysis of samples from NSCLC patients with mutant EGFR indicated a possible connection between UbcH10 expression levels and progression-free survival. Conclusions: In NSCLC, UbcH10 may play a role in the regulation of TKI response via a molecular pathway potentially involving p53 and EGFR. However, further research is needed to fully understand this mechanism. Full article

The present study was designed to characterize the interactions between lecithin liposomes, a model membrane, and either β-carotene or tamoxifen. In addition, the cytotoxicity of liposomal beta-carotene with tamoxifen was screened in vitro in human breast cancer cell lines MCF-7 and MDA-MB-231 in addition to the normal WI38 cell line. All liposomes were nearly spherical and evenly distributed and had fewer aggregates for encapsulated and empty vesicles. Measurements using dynamic light scattering verified that each sample was monodisperse. When tamoxifen is incorporated into liposomal membranes, the zeta potential values tend to decrease. In the test for cytotoxicity using MCF-7 treated cells, the liposomal β-carotene IC₅₀ value was at least 0.45 μg/mL, whereas the IC₅₀ of free β-carotene treated cells was 7.8 μg/mL. For MCF-7 treated cells treated with free tamoxifen, the IC₅₀ was 9.92 μg/mL, but for its liposomal form, it was 20.88 μg/mL. According to the cytotoxicity test using MDA-MB-231 treated cells, the IC₅₀ values for free tamoxifen, free β-carotene, liposomal β-carotene, liposomal tamoxifen, and liposomal tamoxifen β-carotene were 15.5 μg/mL, 38.1 μg/mL, 12.1 μg/mL, 21.2 μg/mL, and 11.4 μg/mL, respectively. This investigation demonstrated that free β-carotene has a more potent cytotoxic impact than tamoxifen. The findings showed that each comet assay variable for the liposomal β-carotene was significantly (p < 0.05) elevated in comparison with tamoxifen and control values. Analysis using flow cytometry revealed that the MCF-7 cells displayed a greater degree of cell apoptosis than the control cells following a 48 h exposure to liposomal β-carotene. Based on available data, a novel treatment plan that includes liposomal β-carotene may boost antitumor activity toward the MCF-7 cancer cell line. The current findings demonstrated that preparations of natural products might be a good substitute for pharmaceutical interventions in the treatment of breast cancer. Full article

Introduction: Radiotherapy is effective for breast cancer treatment but often causes undesirable side effects that impair quality of life. Ultra-high dose rate radiotherapy (FLASH) has shown reduced normal tissue toxicity while achieving comparable tumor growth delay compared to conventional dose rate radiotherapy (CONV). This study evaluated whether FLASH could achieve similar tumor control as CONV with tumor eradication as the primary endpoint, in an orthotopic breast cancer model. Methods: Non-metastatic, orthotopic tumors were generated in the left fourth mammary fat pad using the Py117 mammary tumor cell line in syngeneic C57BL/6J mice. Two sequential irradiation studies were performed using FLASH (93–200 Gy/s) and CONV (0.08 Gy/s) electron beams. Single fractions of 20, 25, or 30 Gy were applied to tumors with varying abdominal wall treatment fields (~3.75 or 2.5 mm treatment margin to tumor). Results: Both FLASH and CONV demonstrated comparable efficacy. Small tumors treated with 30 Gy and larger abdominal wall treatment fields appeared to have complete eradication at 30 days but also exhibited the highest skin toxicity, limiting follow-up and preventing confirmation of eradication. Smaller abdominal wall treatment fields reduced skin toxicity and allowed for extended follow-up, which resulted in 75% tumor-free survival at 48 days. Larger tumors showed growth delay but no eradication. Conclusions: In this preclinical, non-metastatic orthotopic breast cancer model, FLASH and CONV demonstrated equivalent tumor control with single-fraction doses of 20, 25, or 30 Gy. Overall, 30 Gy achieved the highest eradication rate but also resulted in the most pronounced skin toxicity. Full article

The human milk (HM) microbiome is variable and depends on maternal, perinatal, and cultural–environmental factors. The diversity of the HM microbiome is crucial in the development of the child. The aim of the study was to assess the prevalence of bacteria (using culture-based methods) of Polish women with normal BMI, giving birth on time through vaginal delivery. Methods: The research material consisted of human milk and swabs from the areola and nipple, before and after breastfeeding, derived from Polish women (n = 86). Classic culture methods were used to obtain multiple bacteria. Species identification of the grown colonies was performed using MALDI TOF MS (Matrix-Assisted Laser Desorption/Ionization Time of Flight Mass Spectrometry). Results: 120 species of bacteria were isolated, mainly from the genus Streptococcus and Staphylococcus. Species specific only to human milk were identified (belonging to the following genera: Microbacterium, Shewanella, Psychrobacter, Aeromonas, Serratia, Buttiauxella, Lactobacillus, Bifidobacterium) as well as species specific only to areola and nipple swabs after breastfeeding (Acinetobacter lactucae, Moraxella catarrhalis, Corynebacterium pseudodiphtheriticum, Corynebacterium propinquim). It was confirmed that most species were present in all tested materials collected from one patient. Conclusions: The analysis carried out showed the presence of bacteria in the human milk of Polish women, including strains of lactic acid bacteria. The human milk microbiota may significantly influence the formation of the infant’s intestinal microbiota, including some key genera, i.e., Lactobacillus, Bifidobacterium, and Limosilactobacillus, which were also isolated from the tested samples. The data presented here provide new data on culturable bacterial species isolated from breast milk from Polish women giving birth via vaginal delivery and potential routes of transmission from the neonate’s oral cavity. Full article

Hawm Gra Dang Ngah rice (HDNR) is a red rice variety cultivated in Thailand’s southern border region, yet its biological properties have not been extensively studied. This study investigates the effects of HDNR extracts on bioactive constituents, spectral fingerprints, and antioxidant capacities. We evaluated the inhibitory effects of aqueous (HDNR-W) and ethanolic (HDNR-E) extracts on monoamine oxidase (MAO), α-glucosidase, and HMG-CoA reductase activities, as well as their cytotoxicity in normal and cancer cells. The results demonstrated that HDNR-E contained significantly higher concentrations of phenolic compounds, flavonoids, and anthocyanins compared to HDNR-W. In contrast, HDNR-W exhibited greater amino acid content than HDNR-E. FT-IR analysis revealed solvent-specific interactions that influenced compound solubility, highlighting distinct extraction efficiencies. Antioxidant assays showed HDNR-E to be markedly more potent, with superior performance in DPPH, ABTS, metal chelation, and FRAP assays, as evidenced by its lower IC₅₀ values relative to HDNR-W. Furthermore, HDNR-E displayed significantly stronger inhibitory activity against both MAO and α-glucosidase compared to HDNR-W. Conversely, HDNR-W demonstrated greater inhibitory efficacy toward HMG-CoA reductase than HDNR-E. Furthermore, HDNR-E exhibited significant antiproliferative effects against A549 lung cancer and MCF-7 breast cancer cells without affecting normal cells. These results highlight the potential of HDNR-E as a valuable source of bioactive compounds and underscore the importance of solvent selection in enhancing the health benefits of rice extracts. Full article

A fluorescent cell-based assay was developed for the screening of chemicals repressing the expression of human telomerase reverse transcriptase (hTERT). hTERT is reactivated during carcinogenesis and is overexpressed in more than 90% of cancers but is almost silent in normal tissue cells. Because of its critical role in cancer, hTERT is a target in various therapeutic strategies for cancer treatment. In this study, the hTERT promoter was cloned in MCF7 breast cancer cells and used to control the expression of enhanced green fluorescent protein (EGFP). The fluorescence of EGFP indicated the activity of the hTERT promoter, and, in the presence of an hTERT repressor, the EGFP fluorescence signal was reduced as compared to the EGFP fluorescence controlled by the human cytomegalovirus (CMV) promoter, which was not affected by changes in culture conditions and worked as a control. The EGFP reporter cells were cultivated in three-dimensional (3D) microbioreactors to resemble the in vivo tumor physiology and provide in vivo-like responses. The assay’s predictability was demonstrated with three known hTERT inhibitors, pristimerin, epigallocatechin gallate, and n-butylidenephthalide, and further evaluated with five widely used anticancer compounds, doxorubicin, cisplatin, paclitaxel, blasticidin, and tamoxifen. The results showed overall accuracy of over 83.3%, demonstrating the feasibility of using the hTERT promoter with EGFP as a reporter for the screening of potential cancer drugs targeting hTERT. Full article

In recent years, exopolysaccharides (EPSs) have emerged as significant substances due to their impressive biological properties. This research intends to analyze the EPS extracted from probiotic bacteria and assess its various biological activities. The promising probiotic bacteria isolated from human breast milk was isolated and identified as Lactiplantibacillus plantarum B7 by 16S rRNA sequencing. The EPS yield of this strain was quantified as 5.2 g/L. The crude extract (EPSc) was subjected to purification by chromatography on DEAE-cellulose and Sephadex G-100 columns, giving two main fractions named EPSF1 and EPSF2. Structural features were investigated by HPLC, FTIR, GPC and ¹HNMR. Chromatographic analysis indicated that EPSF1 and EPSF2 were composed of mannuronic acid, mannose and glucose in a molar ratio of 2.6:2.15:1.00 and 3.92:2.65:1.00 with a molecular weight of 4.36 × 10⁴ and 5.27 × 10⁵, respectively. Multiple in vitro assays of EPSc, EPSF1 and EPSF2 showed potent radical scavenging activity on DPPH, ABTS, hydroxyl radical scavenging activity (HRS) and superoxide scavenging activity. Also, they showed reducing power of 0.69, 0.61 and 0.58, respectively, at 1000 μg/mL. EPSc, EPSF1 and EPSF2 displayed negligible toxicity against WI-38 human normal lung cells but had cytotoxic effects against human colon cancer (Caco-2), (IC₅₀ = 122.13 ± 0.01, 72.5 ± 0.12 and 81.6 ± 0.1 μg/mL), HepG2 liver cancer (IC₅₀ = 112.5 ± 0.01, 60.3 ± 0.1 and 62.0 ± 0.03 μg/mL) and human prostate cancer (PC3) (IC₅₀ = 109.6 ± 0.03, 65.7 ± 0.01 and 70.3 ± 0.04 μg/mL). While anti-inflammatory as hemolysis inhibition was 79.3 ± 0.05, 93.5 ± 0.05 and 87.9 0.03% at 500 µg/mL, respectively. The results indicate that EPSF1 showed promising antioxidant, antitumor and anti-inflammatory activities. Full article

Extracellular vesicles (EVs) are membrane-bound cargoes secreted by normal and pathological cells. Through their protein, nucleic acid, and lipid cargoes, EVs mediate several cellular processes, such as cell–cell communication, cell development, immune response, and tissue repair. Most importantly, through their enzyme cargo, EVs mediate pathophysiological processes, including the pathogenesis of cancer. In this review, we enumerate several enzymes secreted in EVs (EV enzyme cargo) from cells and patient clinical samples of breast and prostate cancers and detail their contributions to the progression and survival of both cancers. Findings in this review reveal that the EV enzyme cargo could exert cell progression functions via adhesion, proliferation, migration, invasion, and metastasis. The EV enzyme cargo might also influence cell survival functions of chemoresistance, radioresistance, angiogenesis, cell death inhibition, cell colony formation, and immune evasion. While the current literature provides evidence of the possible contributions of the EV enzyme cargo to the progression and survival mechanisms of breast and prostate cancers, future studies are required to validate that these effects are modified by EVs and provide insights into the clinical applications of the EV enzyme cargo in breast and prostate cancer. Full article

Anthocyanins (ACNs) from dark sweet cherries (DSCs) have shown efficacy against breast cancer (BC) cells, particularly triple-negative breast cancer (TNBC) cells, without affecting normal breast cells. This study investigated the impact of ACNs on TNBC cells, focusing on drug resistance mechanisms involving drug metabolism and transport enzymes. Specifically, it was examined whether ACNs influenced Doxorubicin (DOX) metabolism by targeting drug metabolism enzymes (phase I metabolism) and drug transport enzymes (phase III metabolism) in TNBC cells. 4T1 TNBC cells were treated with ACNs, DOX, and the combination of both (ACN-DOX). Results showed a synergistic inhibition of cell viability by ACNs and DOX. In addition, the modulation of phase I drug-metabolizing enzymes was exerted by ACNs, reducing the activity of cytochrome P450 (CYP) enzymes induced by DOX. A reduction of drug efflux by ACNs was shown by decreasing P-glycoprotein (P-gp) activity, leading to a higher intracellular accumulation of DOX. These effects were confirmed using CYP and P-gp inducers and inhibitors, showing their impact on cell viability. In conclusion, the combination of ACNs with DOX has the potential to lower DOX doses, enhance its efficacy, and possibly reduce side effects, offering a promising approach for TNBC treatment. Full article

Cancer, a leading cause of premature death, arises from genetic and epigenetic mutations that transform normal cells into tumor cells, enabling them to proliferate, evade cell death, and stimulate angiogenesis. Recent evidence indicates that chemokines are essential in tumor development, activating receptors that promote proliferation, invasion, and metastasis. The CXCR4/CXCL12 signaling pathway is gaining attention as a promising target for cancer therapy. CXCR4, a chemokine receptor, is often overexpressed in various types of cancer, including kidney, lung, brain, prostate, breast, pancreas, ovarian, and melanomas. When it binds to its endogenous ligand, CXCL12, it promotes cell survival, proliferation, and migration, crucial mechanisms for the retention of hematopoietic stem cells in the bone marrow and the movement of lymphocytes. The extensive expression of CXCR4 in cancer, coupled with the constant presence of CXCL12 in various organs, drives the activation of this axis, which in turn facilitates angiogenesis, tumor progression, and metastasis. Given the detrimental role of the CXCR4/CXCL12 axis, the search for drugs acting selectively against this protein represents an open challenge. This review aims to summarize the recent advancements in the design and development of CXCR4 antagonists as potential anticancer agents. Full article

In the absence of long-term hydrologic records, field-measured hydrologic indicators are useful for inferring past wetland hydrologic conditions, which can support research, regulation, and restoration. Inflection points on the buttresses of pondcypress trees (Taxodium ascendens) are frequently used in west-central Florida to estimate cypress wetland high water levels, known as normal pool. However, little is known about how this indicator develops. A method to estimate tree age using diameter at breast height was developed for Florida pondcypress, which can be used by forested wetland managers to constrain the maximum potential age of hydrologic indicators in groups of cypress trees. This model was applied to a waterbody with a complex history of hydrologic alterations. The waterbody had two distinct populations of buttress inflection elevations, corresponding to historic versus current water level regimes. This represents one of the first documented instances in the literature where a waterbody showed multiple buttress inflection populations in the absence of soil subsidence. This work underscores the need to consider the development timelines when interpreting the hydrologic meaning of indicator elevations. Full article