Search Results (30)

Background: Neoadjuvant systemic therapy (NST), whose primary purposes include response assessment and treatment individualization, is a key strategy in the treatment of HER2-positive breast cancer. This study investigated the predictive value of the magnetic resonance imaging (MRI)-derived tumor volume reduction rate (δV1) for the early identification of pathological complete response (pCR) during NST and established clinically applicable δV1 thresholds for patient stratification. Methods: HER2-positive breast cancer patients who received THP (taxane, trastuzumab, pertuzumab) followed by epirubicin/cyclophosphamide (EC) were enrolled. MRI was performed at baseline, after THP, and after EC. Tumor volumes were manually segmented using 3D Slicer, and δV1/δV2 were calculated via Python (version3.13). Longest diameter reduction rates (δL1/δL2) were recorded. pCR (ypT0/is ypN0) was the primary endpoint. Receiver operating characteristic (ROC) analysis determined predictive accuracy, and logistic regression identified independent predictors. Thresholds for δV1 were explored, and subgroup analyses were conducted by hormone receptor (HR) and human epidermal growth factor receptor 2 (HER2) status. Results: Overall, 59.3% of patients achieved pCR. δV1 demonstrated superior predictive accuracy compared with longest diameter reduction (δL1), with an AUC of 0.745 (95% CI: 0.642–0.847) vs. 0.634 (95% CI: 0.512–0.757). A δV1 cutoff of 0.85 discriminated responders (68.4% vs. 41.4%, p = 0.016), while one of 0.91 represented the optimal predictive threshold. In multivariate analysis, δV1 was independently associated with pCR (OR = 1227.1, 95% CI: 6.86–219,562; p = 0.007), along with HER2 3+ expression (OR = 4.24, 95% CI: 1.26–14.31; p = 0.020). Among HR-positive patients, δV1 < 0.93 identified a subgroup with significantly lower pCR rates (19.0% vs. 81.0%, p < 0.001). Conclusions: δV1 is a reliable and early MRI-based imaging biomarker for predicting pCR in HER2-positive breast cancer. Defining thresholds such as 0.85 and 0.91 supports early therapeutic stratification and may help identify patients who could benefit from anthracycline-containing regimens. Full article

Excessive accumulation of lipid droplets (LDs), their dynamics, and lipotoxicity are critical factors in the progression of metabolic disorders, including diabetic nephropathy. This study investigates the effects of yomogi tea (Mugwort tea), specifically its leaf infusion (YL) and powdered infusion (YP), on lipid metabolism in human kidney proximal tubular epithelial HK-2 cells under lipotoxic conditions induced by palmitic acid (PA). Both YL and YP significantly reduced intracellular triglyceride (TG) and free fatty acid (FFA) levels, with YP showing a trend toward greater efficacy. Mechanistic analysis revealed that yomogi tea regulates lipid metabolism by significantly downregulating mRNA expression of FAS and upregulating that of the lipolytic ATGL, while SCD-1 mRNA expression remained largely unchanged. Furthermore, yomogi tea reduced LD size and neutral lipid content, potentially enhancing lipid hydrolysis efficiency and mitigating lipotoxic effects. These findings highlight the potential of yomogi tea as a natural agent for regulating lipid metabolism and reducing lipotoxicity, offering promise for managing lipid metabolism-related disorders. Full article

Background/Objectives: Cataract surgery often reveals preexisting corneal astigmatism, which can be corrected using a toric intraocular lens (T-IOL). However, postoperative T-IOL rotation may compromise correction. We investigated T-IOL rotation, focusing on deployment time and proximity to the posterior capsule (PC), using intraoperative optical coherence tomography (iOCT). Methods: Six different T-IOL models were inserted into acrylic simulated lens capsule models under different tacking durations (5 s, 30 s, and 60 s) and temperature conditions (23 °C, 28 °C, and 32 °C). The selection criteria for porcine lenses for examination required that they match human lens dimensions, typical of those used to train cataract surgeons. T-IOL misalignment due to vibration was assessed. Additionally, the impact of temporary intraocular pressure (IOP) reduction on T-IOL proximity to the PC was measured using iOCT in porcine eyes. Results: Tacking time and temperature independently affected T-IOL deployment, with shorter tacking durations and higher temperatures leading to faster deployment. Among lenses tested under identical tacking time and temperature conditions, iSert Micro Toric Aspheric 1-Piece IOL (355T3) had the slowest expansion time, while Avansee™ Preload 1-Piece Toric (YP-T3) had the fastest. Porcine eyes with a corneal white-to-white major axis < 16.0 mm fell within the 95% confidence interval for matching human lens size. Temporarily reducing IOP during surgery improved T-IOL adhesion to the PC, reducing both the occurrence and degree (from 14.0° to nearly 0°) of postoperative rotation. Conclusions: Optimal T-IOL deployment, temporary IOP reduction during surgery, and enhanced adhesion to the PC can reduce the risk and degree of T-IOL rotation. Intraoperative iOCT aids in monitoring T-IOL positioning, which is essential to prevent rotation. Accumulated fluid between the T-IOL and PC may contribute to rotation, which requires further investigation. These findings provide practical strategies for enhancing T-IOL stability and improving the effectiveness of astigmatism correction in cataract surgery. Full article

Background: Colon cancer is one of the most prevalent gastrointestinal malignancies worldwide, with high mortality and limited therapeutic options. Puerarin, a flavonoid compound derived from Pueraria lobata, has shown anticancer potential, but its molecular mechanisms against colon cancer remain unclear. Methods and Results: In this study, human colon cancer Caco-2 cells were treated with various concentrations of puerarin. Cell proliferation, migration, invasion, epithelial–mesenchymal transition (EMT), and apoptosis were evaluated using CCK-8, wound healing, Transwell, immunofluorescence, flow cytometry, and Western blot assays. Puerarin significantly inhibited Caco-2 cell proliferation in a dose- and time-dependent manner. It suppressed migration and invasion by increasing E-cadherin and reducing Vimentin expression. Apoptosis was induced via upregulation of BAX and downregulation of Bcl-2. Network pharmacology and KEGG analysis suggested PI3K/AKT signaling as a core regulatory pathway. Western blotting confirmed that puerarin reduced phosphorylation of PI3K and AKT. PI3K activator 740 Y-P promoted EMT and inhibited apoptosis, whereas puerarin and the PI3K inhibitor LY294002 reversed these effects. Conclusions: Puerarin exerts significant antitumor effects on Caco-2 colon cancer cells by inhibiting proliferation, migration, and EMT, while promoting apoptosis. These effects are mediated primarily through suppression of the PI3K/AKT signaling pathway. This study provides a theoretical basis for the use of puerarin as a natural therapeutic agent in colon cancer treatment. Full article

Clostridium novyi is a common pathogen in domestic animals and humans, and alpha-toxin is the main cause of its pathogenesis. Because it is a fastidious organism, obtaining alpha-toxin is expensive. Therefore, we proposed an in silico study to synthesize epitopes in cultures of Escherichia coli BL21 pLysS (DE3). First, we used a stirred-tank bioreactor, developing a dry mass yield (DMY) of 0.77 g/L in batch cultures and 1.03 g/L in fed-batch cultures, without acetic acid production. With scale-up using a system without mechanical agitation, there was a higher DMY (1.20 g/L) with 0.56 mmol/mL of alpha-toxin epitope 1 (DE3/Ep1) and 0.61 mmol/mL of alpha-toxin epitope 2 (DE3/Ep2), with a similar profile for O2 consumption, glucose, and no acetic acid production. The kinetic parameters µ(h⁻¹), YX/S, YP/S, QP, and QX did not differ significantly; however, the kinetic data were superior. Our results suggest that in silico tools allow epitope selection and bioprocess standardization. This system provides cost savings and technological advances for the veterinary vaccine industry. Full article

Background: Naringenin has demonstrated potential therapeutic effects against cigarette smoke-induced lung injury; however, its underlying mechanisms of regulating matrix metalloproteinase-9 (MMP-9) in alveolar macrophages remain unclear. Methods: The regulatory mechanisms of naringenin in cigarette smoke extract (CSE)-induced alveolar macrophages were investigated using proteomics, and then, naringenin’s targets were further validated by Western blot, molecular docking, molecular dynamics (MD) simulations, cellular thermal shift assay (CETSA), and enzyme activity assay. Results: The proteomics revealed that the PI3K/AKT signaling pathway might play a crucial role in naringenin’s inhibition of MMP-9. Western blot analysis confirmed that naringenin significantly inhibited CSE-upregulated PI3K/AKT signaling pathway and reduced MMP-9 expression in MH-S cells. Notably, the PI3K activator 740Y-P reversed naringenin’s effects on MMP-9. Additionally, molecular docking, MD simulations, and CETSA identified PI3K p85alpha as the potential binding site for naringenin, and naringenin markedly inhibited CSE-induced PI3K activity. In in vitro experiments, naringenin inhibiting MMP-9 secretion in alveolar macrophages contributed to alleviating elastin and E-cadherin damage in alveolar epithelial cells. Furthermore, naringenin effectively suppressed CSE-induced MMP-9 secretion in primary mouse alveolar macrophages and human THP-1-differentiated macrophages. Conclusions: Our findings revealed that naringenin, a potential candidate for treating smoking-induced lung injury, directly targeted PI3K p85alpha, inhibiting PI3K activity and MMP-9 expression in CSE-induced alveolar macrophages via suppressing the PI3K/AKT signaling pathway. Full article

Acrylamide, a harmful substance generated during the normal thermal treatment of foods, has been shown to adversely affect human health, particularly the vital intestinal barrier function. Meanwhile, natural polysaccharides are recognized to exert an important biofunction in the intestine by protecting barrier integrity. In this study, the non-starch, water-soluble, and nondigestive yam polysaccharide (YP) was extracted from fresh Chinese yam, while two selenylated derivatives with different extents of selenylation were prepared via the HNO₃-Na₂SeO₃ reaction system, and designated as YPSe-I and YPSe-II, respectively. Their protective activities and the associated molecular mechanisms of these substances against acrylamide-induced damage in rat intestinal epithelial (IEC-6) cells were thereby investigated. The experimental results demonstrated that the selenium contents of YPSe-I and YPSe-II were 0.80 and 1.48 g/kg, respectively, whereas that of the original YP was merely 0.04 g/kg. In IEC-6 cells, in comparison with YP, both YPSe-I and YPSe-II showed higher efficacy than YP in alleviating acrylamide-induced cell toxicity through promoting cell viability, suppressing the release of lactate dehydrogenase, and decreasing the generation of intracellular reactive oxygen species. Both YPSe-I and YPSe-II could also manifest higher effectiveness than YP in maintaining cell barrier integrity against the acrylamide-induced barrier disruption. The mentioned barrier protection was achieved by increasing transepithelial electrical resistance, reducing paracellular permeability, facilitating the distribution and expression of F-actin between the cells, and up-regulating the production of three tight junctions, namely ZO-1, occludin, and claudin-1. Additionally, acrylamide was observed to trigger the activation of the MAPK signaling pathway, thereby leading to cell barrier dysfunction. In contrast, YPSe-I and particularly YPSe-II were capable of down-regulating two MAPK-related proteins, namely p-p38 and p-JNK, and thereby inhibiting the acrylamide-induced activation of the MAPK signaling pathway. Moreover, YPSe-II in the cells was consistently shown to provide greater barrier protection than YPSe-I. In conclusion, chemical selenylation of YP could cause higher activity in mitigating acrylamide-induced cytotoxicity and intestinal barrier dysfunction, while the efficacy of activity enhancement was positively affected by the selenylation extent. Full article

Introduction: Data are lacking on the optimal neoadjuvant systemic treatment (NST) for women with hormone receptor-positive (HR+) human epidermal growth factor receptor 2-positive (HER2+) breast cancer if they are unfit to receive the combination of chemotherapy and anti-HER2 therapy. The aim of this study was to determine whether the rates of ypT0 and ypN0 differ between patients treated with neoadjuvant endocrine therapy (NET) versus NET combined with anti-HER2 therapy (NET+aHER2). Materials and Methods: Data from the Netherlands Cancer Registry were analysed to identify women diagnosed with primary HR+/HER2+ breast cancer between 2008 and 2019, treated with either NET or NET+aHER2. The ypT0 and ypN0 rates were analysed (using uni- and multivariable logistic regression analyses, as applicable) in relation to the characteristics of the patient, the tumour, and the treatment. Results: Of the 190 patients identified (median age 77), 150 had been treated with NET and 40 with NET+aHER2. Patients with clinically node-positive disease (cN+) were significantly more likely to have been treated with NET+aHER2 (p = 0.029). The ypT0 rate was significantly higher after NET+aHER2, with 10.0% (4/40) versus 1.3% (2/150) following NET (p = 0.019). The ypN0 rate was significantly higher after NET+aHER2, with 25.0% (6/24) versus 5.5% (3/55) following NET in the cN+ patients (p = 0.020) and 81.3% (13/16) versus 55.8% (53/95) after NET in the cN- patients (p = 0.047). In the cN- patients, the ypN0 status was independently associated with age (p = 0.008) and the administration of NET+aHER2 (p = 0.016). Conclusions: The rates of ypT0 and ypN0 in women with HR+/HER2+ breast cancer treated with NST was significantly higher following NET+aHER2 than after NET. Full article

The use of neoadjuvant systemic therapy (NST) has become increasingly important in the treatment of breast cancer because of its various advantages. These include the ability to downstage tumors without compromising locoregional control and the potential to obtain valuable information about clinical and biological response to therapy with implications for individual prognoses. Surgical response assessment paves the way for response-adapted therapy, and pathological complete response (pCR; defined as ypT0/is ypN0) serves as an additional endpoint for drug development trials. Recommended NST regimens commonly consist of anthracyclines and taxane, with dose-dense anthracyclines and weekly paclitaxel often preferred, whenever feasible. For patients with human epidermal growth factor receptor-2 (HER2)-positive tumors, dual anti-HER2 therapy (trastuzumab and pertuzumab) is indicated together with NST in case of elevated risk of recurrence. For patients with triple-negative breast cancer (TNBC), adding carboplatin to NST correlates with improved pCR and survival rates, as does the addition of immune checkpoint inhibitors. For hormone receptor (HR)-positive/HER2-negative cancers, emerging data on NST including immune checkpoint inhibitors may elevate the significance of NST in high-risk luminal breast cancer. Here, we present a synthesis of the results from neoadjuvant clinical trials that aim at optimizing treatment options for patients with high-risk breast cancer. Full article

The yellow pea (Pisum sativum L. ‘Eso’, sin. Lathyrus oleracaeus Lam.(YP)) is an annual herbaceous plant that belongs to the Fabaceae family. Peas, along with other legumes, are an excellent source of proteins and essential amino acids; the yellow variety is known for maintaining a good protein profile even if subjected to industrial processing. However, the presence of antinutrients, such as phytates and oligosaccharides, limits its consumption as a fresh legume to its use as a source of isolated proteins or for animal feed. The aim of the study is to evaluate the changes in the entire phytochemical profile of YP seeds as a function of the harvest time. YPs harvested at about 40, 50, 60, and 70 days from sowing were examined by high-resolution NMR spectroscopy employing ¹H-NMR, ¹H-¹H TOCSY, and ¹H-¹³C HSQC. In total, 40 molecular species were identified and quantified; it was observed that there was a monotonous decrease in amino acids, carbohydrates, and secondary metabolites as a function of time. Antinutrient levels increased, but only in later sampling times. This study identified the optimal harvest time for yellow peas “Eso” in the fortieth day from sowing, adding new information about the best nutritional outcome for humans. Full article

The crucial physiological process of heme breakdown yields biliverdin (BV) and bilirubin (BR) as byproducts. BV, BR, and the enzymes involved in their production (the “yellow players—YP”) are increasingly documented as endogenous modulators of human health. Mildly elevated serum bilirubin concentration has been correlated with a reduced risk of multiple chronic pro-oxidant and pro-inflammatory diseases, especially in the elderly. BR and BV per se have been demonstrated to protect against neurodegenerative diseases, in which heme oxygenase (HMOX), the main enzyme in the production of pigments, is almost always altered. HMOX upregulation has been interpreted as a tentative defense against the ongoing pathologic mechanisms. With the demonstration that multiple cells possess YP, their propensity to be modulated, and their broad spectrum of activity on multiple signaling pathways, the YP have assumed the role of an adjustable system that can promote health in adults. Based on that, there is an ongoing effort to induce their activity as a therapeutic option, and natural compounds are an attractive alternative to the goal, possibly requiring only minimal changes in the life style. We review the most recent evidence of the potential of natural compounds in targeting the YP in the context of the most common pathologic condition of adult and elderly life. Full article

Campylobacter infections in humans are traced mainly to poultry products. While vaccinating poultry against Campylobacter could reduce the incidence of human infections, no vaccine is yet available on the market. In our previous study using a plasmid DNA prime/recombinant protein boost vaccine regimen, vaccine candidate YP437 induced partial protective immune responses against Campylobacter in broilers. In order to optimise vaccine efficacy, the vaccination protocol was modified using a protein prime/protein boost regimen with a different number of boosters. Broilers were given two or four intramuscular protein vaccinations (with the YP437 vaccine antigen) before an oral challenge by C. jejuni during a 42-day trial. The caecal Campylobacter load, specific systemic and mucosal antibody levels and caecal microbiota in the vaccinated groups were compared with their respective placebo groups and a challenge group (Campylobacter infection only). Specific humoral immune responses were induced, but no reduction in Campylobacter caecal load was observed in any of the groups (p > 0.05). Microbiota beta diversity analysis revealed that the bacterial composition of the groups was significantly different (p ≤ 0.001), but that vaccination did not alter the relative abundance of the main bacterial taxa residing in the caeca. The candidate vaccine was ineffective in inducing a humoral immune response and therefore did not provide protection against Campylobacter spp. infection in broilers. More studies are required to find new candidates. Full article

Bacterial infections seriously threaten human safety. Therefore, it is very important to develop a method for bacterial detection and treatment with rapid response, high sensitivity, and simple operation. A peptide CF₄KY^P (C, cysteine; F₄, phenylalanine tetrapeptide; K, lysine; Y^P, phosphorylated tyrosine) functionalized gold nanoparticle (AuNPs-CF₄KY^P) was synthesized for simultaneous detection and treatment of bacteria based on bacterial alkaline phosphatase (ALP). In solution, ALP can induce AuNPs-CF₄KY^P aggregation and produce significant color changes. After encountering bacteria, monodisperse AuNPs-CF₄KY^P can aggregate/assemble in situ on the surface of the bacterial membrane, change the color of the solution from wine red to grey, destroy the bacterial membrane structure, and induce the production of a large number of reactive oxygen species within the bacteria. The absorption change of AuNPs-CF₄KY^P solution has a good linear relationship with the number of bacteria. Furthermore, the aggregation of AuNPs-CF₄KY^P kills approximately 80% of Salmonella typhimurium. By combining enzyme-instructed peptide self-assembly technology and colorimetric analysis technology, we achieve rapid and sensitive colorimetric detection and killing of bacteria. Full article

Hexavalent chromium [Cr (VI)] is a highly toxic and hazardous contaminant that poses serious health risks to both humans and the environment. Its presence in water sources can lead to severe health issues, including various types of cancer and respiratory ailments. Therefore, developing efficient and effective methods for Cr (VI) removal is crucial in ensuring safe and clean water supplies. The aim of this research is the environmentally responsible elimination of hexavalent chromium by bioadsorption using corn residues (CR), palm fiber (PF), and the peels of yam (YP), cassava (CP), and cocoa (CH). The study was conducted with varying levels of pH, bioadsorbent quantity, temperature, and adsorbent particle size at 200 rpm, with an initial concentration of 100 mg/L and 24 h of contact time to improve the adsorption efficiency. The process variables were evaluated and optimized using the statistical technique response surface methodology (RSM). The SEM-EDS analysis revealed that the predominant elements in the structure of the bioadsorbents were carbon and oxygen. Furthermore, the adsorption process led to the incorporation of Cr (VI) into the structure of the biomaterials, as indicated by their EDS spectra. The maximal adsorption efficiency of 99.11% was obtained at pH 2, bioadsorbent dose of 0.03 mg, 30 °C, and 0.5 mm of particle size. Various equilibrium isotherms were utilized to fit and analyze the adsorption data. The assessed maximum adsorption capacities were 38.84, 56.88, 52.82, 138.94, and 240,948.7 mg/g for YP, PF, CP, CH, and CR, respectively. The adsorption data exhibited conformity with the Freundlich and Redlich–Peterson isotherm models (R² = 0.95), indicating that the phenomenon occurs in a multilayer. Pseudo-second order and Elovich kinetic models adjusted the kinetics of chromium (VI), suggesting that the mechanism could be controlled by chemisorption. Therefore, the residual biomasses evaluated can serve as a cost-effective adsorbent for Cr (VI) removal, and the use of RSM enables efficient modeling and prediction of the adsorption process. Full article

The study was aimed at identifying endogenous proteins which assist or impede the permeabilized state in the cell membrane disrupted by nsEP (20 or 40 pulses, 300 ns width, 7 kV/cm). We employed a LentiArray CRISPR library to generate knockouts (KOs) of 316 genes encoding for membrane proteins in U937 human monocytes stably expressing Cas9 nuclease. The extent of membrane permeabilization by nsEP was measured by the uptake of Yo-Pro-1 (YP) dye and compared to sham-exposed KOs and control cells transduced with a non-targeting (scrambled) gRNA. Only two KOs, for SCNN1A and CLCA1 genes, showed a statistically significant reduction in YP uptake. The respective proteins could be part of electropermeabilization lesions or increase their lifespan. In contrast, as many as 39 genes were identified as likely hits for the increased YP uptake, meaning that the respective proteins contributed to membrane stability or repair after nsEP. The expression level of eight genes in different types of human cells showed strong correlation (R > 0.9, p < 0.02) with their LD₅₀ for lethal nsEP treatments, and could potentially be used as a criterion for the selectivity and efficiency of hyperplasia ablations with nsEP. Full article