Search Results (8,307)

The antibacterial activity of 18 phenolic compounds, including flavonoids and phenolic acids, against organisms of Escherichia coli, Klebsiella pneumoniae, and Proteus vulgaris that are resistant to several drugs was assessed in this study using the agar diffusion method. The strain’s strong resistance was confirmed by antibiotic susceptibility testing, which used fourteen drugs and only found inhibition zones for five of them. Out of the polyphenols, four compounds were effective against P. vulgaris, five against K. pneumoniae, and twelve against E. coli bacteria. The greatest inhibitory zone (18.75 ± 0.25 mm) against E. coli was shown by propyl gallate, an ester of gallic acid. Activity was significantly impacted by structural changes. Propyl substitution increased antibacterial activities across all strains, while methoxy substitution decreased them. The antibacterial effectiveness was reduced by the hydroxylation of flavonoids and the C3–C4 dihydroxylation of cinnamic acid. Propyl gallate primarily had antagonistic effects, while combination experiments demonstrated additive, synergistic, and antagonistic interactions. Propyl gallate (ΔG = −7.5 kcal/mol) exhibited substantial binding affinities with TEM-1 and NDM-1 β-lactamases via hydrogen and hydrophobic interactions, according to molecular docking. These results demonstrate propyl gallate as a viable antibacterial adjuvant option and validate the structure–activity relationship of phenolic compounds. Full article

Background/Objectives: Cervical cancer outcomes based on geographic location of residence reveal inconsistent patterns, and most of the evidence is from the United States. This retrospective study aimed to investigate whether there existed a difference in overall survival (OS) and recurrence-free survival (RFS) between individuals living within a Canadian city with a tertiary care centre versus those living remotely within a large catchment area (up to >1000 km travel distance), including a sizeable rural component. Methods: Surgically treated cervical cancer patients from 2000 to 2016 were included. Patients were treated with either radical hysterectomy, trachelectomy, or simple hysterectomy. Adjuvant treatment was provided depending on surgical pathology. OS and RFS were estimated using Kaplan–Meier curves and cumulative incidence curves. Results: Two hundred and eighty-two patients with surgically treated cervical cancer were included: 185 patients living within urban city limits and 97 patients living rurally. There were no significant baseline differences between groups. No significant difference in OS or RFS was found, even after adjusting for death as a competing risk for RFS. The median time to surgery for residents living within versus outside the city was 84 vs. 66 days, respectively, although this difference was not statistically significant (p = 0.3179). Conclusions: This is the first Canadian study to examine an association between survival and distance to care for cervical cancer. Full article

Background and Objectives: Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive, heterogeneous, and lethal human malignancies, underscoring the urgent need for novel, targeted therapeutic strategies for neo(adjuvant) individualized treatment. The epidermal growth factor receptor family (ErbB) is directly involved in abnormal cell proliferation and tumor growth. The overexpression and amplification of HER2 and HER3 have emerged as key molecular events in pancreatic ductal adenocarcinoma. The aim of this study was to evaluate these membrane receptors’ overexpression in relation to pTNM staging, perineural and lymphovascular invasion, and tumor volume in order to obtain the immunohistochemical profile and enhance the development of a targeted and personalized therapy. Materials and Methods: An observational analytical cohort study included patients with histopathologically naïve, confirmed PDAC who underwent cephalic pancreatoduodenectomy at a national high-volume referral center between 2017 and 2022. Archived surgical specimens were retrieved and examined using a tissue microarray technique in two separate pathology departments by two independent pathologists. Results: HER2 positivity was found in 25 cases, of which 84% had lymphatic invasion, 50% had vascular invasion, and 84% had perineural invasion. Patients with HER3 positivity had lymphatic invasion (82.5%), perineural invasion (79.4%), and vascular invasion (38.1%). Combined HER2 and HER3 positivity was present in 19 cases, and these patients had 84.2% perineural invasion. Conclusions: HER2 and HER3 overexpression often coexisted with pathological features, such as perineural invasion, in cases of combined HER2 and HER3 positivity. These findings support the involvement of the ErbB receptor family in pancreatic carcinogenesis and suggest their potential as targets for future (neo)adjuvant therapeutic strategies. Full article

Background/Objectives: Sulfated polysaccharides from Spirulina platensis have shown various promising biological activities, but their anticancer effects in lung cancer models remain poorly characterized. In this study, sulfated polysaccharide-rich fractions (SPPs) were tested on A549 non-small cell lung cancer (NSCLC) cells to evaluate their cytotoxic, oxidative, and immunomodulatory activity. Methods: The potential of SPPs to interfere with A549 cell viability, to modulate intracellular reactive oxygen species (ROS) levels, to produce pro-inflammatory effects, and to induce apoptosis was evaluated. Co-administration experiments were also performed using Gefitinib, a drug commonly used in NSCLC therapy. Non-cancerous human bronchial epithelial cells (16HBE) were included to assess the ability of SPPs to selectively target tumoral cells. Results: Our findings show that SPPs significantly reduced A549 cell viability in a concentration-dependent manner and increased ROS levels. This effect was associated with apoptotic DNA fragmentation and modulation of apoptosis-related genes, including upregulation of BAX and CASP-9, and downregulation of BCL-2, MTOR, and BIRC5. SPPs also induced a controlled pro-inflammatory response by increasing ACE2, NF-κB1, and CCL2 expression while reducing COX-2 levels. In co-administration experiments with Gefitinib, a cancer drug used to treat NSCLC, enhanced cytotoxic and pro-apoptotic effects were observed. Importantly, at active concentrations (150–250 µg/mL) SPPs were not found to produce cytotoxicity or apoptosis in 16HBE cells. Conclusions: Overall, these findings suggest that SPPs may selectively target NSCLC cells by promoting redox imbalance, apoptosis, and immune response, without affecting healthy cells, supporting their potential as natural adjuvants in lung cancer treatment. Full article

Despite tremendous scientific efforts aimed at glioblastoma’s (GB) ability to escape therapeutic attempts, the concern remains unsolved. Postbiotics, metabolites, and macromolecules of probiotic bacteria could become adjuvant therapeutics both dealing with cellular events constituting tumor therapy escape mechanisms and protecting normal cells from therapy-induced damage. The study aims to evaluate the dual potential of postbiotics obtained from lactic acid bacteria, L. plantarum and L. rhamnosus, on patient-derived and commercially available GB and normal cells alone and in combination with chemotherapeutic and irradiation oncotreatment regimens. Postbiotic mixtures (PMs) show cytoprotective potential against a new anti-cancer agent—ARA12—on astrocytes and cytoprotective action to irradiated normal fibroblast cells. Although GB cells’ apoptotic response varied between patient-derived cells, both PMs exert cytotoxic or cytostatic effects alone and, in most of the studied therapeutic combinations, on all tested GB cell lines. In particular, L. plantarum PM alleviates treatment escape, possibly shifting the tumor drug response from senescence to apoptosis. The results suggest that postbiotic-based adjunctive treatment could potentiate the therapeutic effect toward neoplastic cells, while alleviating chemotherapy’s adverse effects, helping clinicians to tackle the issue of therapy resistance and improve patients’ comfort. Full article

Background/Objectives: Triple negative breast cancer (TNBC) is an aggressive subtype treated primarily with chemotherapy, which often leads to drug resistance (DR) and reduced effectiveness. Phytochemicals, including anthocyanins from dark sweet cherry (ACN), have emerged as potential adjuvants to overcome DR, though mechanisms remain unclear. This study examines ACN effects on canonical and non-canonical antioxidant pathways (Nrf2-Keap1 and p62) as a mechanism to overcome DR in 4T1 TNBC cells with acquired DR. Methods: Two conditions were tested: ACN with basal doxorubicin (DOX) as resistance-maintaining conditions and ACN with DOX at IC₅₀ to induce oxidative stress (OS). Results: Under resistance-maintaining conditions, ACNs activated the canonical Nrf2-Keap1 pathway at high doses, which can potentially contribute to DR development due to its cellular protection effects. However, at a low dose, ACN did not trigger an antioxidant response linked to GST and GGT enzyme activities and instead impaired autophagy, increasing OS. Under OS, ACN activated the non-canonical antioxidant pathway mediated by p62 while deactivating Nrf2, leading to autophagy-induced cell death and further impairing autophagy at a low dose. Notably, inflammation persisted at both treatment levels without being relieved, keeping stress signaling active. At both conditions, ACN at doses likely attainable under physiological conditions effectively impaired autophagy and elevated OS, resulting in cell death. Conclusions: These results underscore the context-dependent dual function of polyphenols in cancer therapy, demonstrating their potential to enhance cellular sensitivity to chemotherapy and providing guidance for their strategic use as adjuvants in treating TNBC and overcoming DR. However, this study was limited to a single cell line derived from a murine model. Future research should include comparative studies using human TNBC cell lines to validate these findings and better assess their translational relevance. Full article

Identifying probiotics that modulate the gut–brain axis is vital for non-pharmacological Alzheimer’s disease (AD) therapy. Through a staged screening from transgenic Drosophila to a D-galactose/AlCl₃-induced murine model, Lactobacillus acidophilus LA4 and Lacticaseibacillus paracasei F5 were prioritized for their ability to improve climbing indices and reduce Aβ deposition and AChE activity. In AD mice, LA4 and F5 significantly ameliorated cognitive deficits and anxiety-like behaviors. Mechanistically, both strains reduced hippocampal Aβ_1–42 and p-Tau levels, inhibited AChE, suppressed pro-inflammatory cytokines (TNF-α, IL-6, IL-1β), and enhanced antioxidant enzymes (SOD, GSH-Px). 16S rRNA analysis revealed restored Firmicutes/Bacteroidetes ratios and enrichment of SCFA-producers (Muribaculaceae, Dubosiella). Metabolomics highlighted remodeled purine and arginine pathways, with strain-specific effects on primary bile acid biosynthesis/sphingolipid metabolism (LA4) and butanoate metabolism/nicotinate and nicotinamide metabolism (F5). Consequently, LA4 and F5 alleviate AD pathology by restructuring microbial and metabolic profiles, thereby mitigating neuroinflammation and oxidative stress. These findings confirm the potential of specific probiotics as functional food ingredients for the prevention and adjuvant treatment of neurodegenerative diseases. Full article

Nanotechnology is becoming a key tool in plant biotechnology, enabling nanoparticles (NPs) to deliver biomolecules with high precision and to enhance plant and tissue resilience under stress. However, the literature remains fragmented across genetic delivery, in vitro regeneration, stress mitigation, and germplasm cryopreservation, and it still lacks standardized, comparable protocols and robust long-term safety assessments—particularly for NP use in cryogenic workflows. This review critically integrates recent advances in NP-enabled (i) genetic engineering and transformation, (ii) tissue culture and regeneration, (iii) nanofertilization and abiotic stress mitigation, and (iv) cryopreservation of plant germplasm. Across these areas, the most consistent findings indicate that NPs can facilitate targeted transport of DNA, RNA, proteins, and regulatory complexes; modulate oxidative and osmotic stress responses; and improve regeneration performance in recalcitrant species. In cryopreservation, selected nanomaterials act as multifunctional cryoprotective adjuvants by suppressing oxidative injury, stabilizing cellular membranes, and improving post-thaw viability and regrowth of sensitive tissues. At the same time, NP outcomes are highly context-dependent, with efficacy governed by dose, size, and surface chemistry; formulation; plant genotype; and interactions with culture media or vitrification solutions. Evidence of potential phytotoxicity, persistence, and biosafety risks highlights the need for harmonized reporting, mechanistic studies on NP–cell interfaces, and evaluation of environmental fate. Expected outcomes of this review include a consolidated framework linking NP properties to biological endpoints, identification of design principles for application-specific NP selection, and a set of research priorities to accelerate the safe and reproducible translation of nanotechnology into sustainable plant biotechnology and long-term germplasm preservation. Full article

Background: Low-grade fibromyxoid sarcoma (LGFMS) is a rare malignant fibroblastic tumor that often appears deceptively benign. Accurate diagnosis is challenging due to its variable morphology and low mitotic activity. This systematic review provides a comprehensive overview of LGFMS and its subtypes. Methods: A systematic search of PubMed and Embase up to September 2025 identified 273 studies, complemented by four institutional cases from Amsterdam UMC. Individual patient data were pooled to analyze clinical presentation, diagnostic approaches, treatment modalities, and outcomes. Results: In total, 773 patients were included, with a median age of 35 years and equal gender distribution. Tumors were predominantly deep-seated (80%), most commonly located in the thigh or pelvis. MUC4 positivity (96%) and FUS-CREB3L2 fusion (47%) were the most consistent diagnostic markers. Surgery was the mainstay of treatment (98%), with R0 resection achieved in 36% of cases and R1 in 15%. Adjuvant therapies, including chemotherapy and radiotherapy, were rarely used and showed limited efficacy. After a median follow-up of 3.0 years, 19% developed local recurrence and 21% developed metastases. R0 resections were associated with significantly better recurrence-free survival than R1 resection (p < 0.05). Conclusions: LGFMS exhibits indolent histology but potential for late recurrence and metastasis, warranting prolonged radiological follow-up and multicenter studies to evaluate adjuvant strategies. Full article

Lipid A is a component of lipopolysaccharide (LPS) of Gram-negative bacteria. Previously, we demonstrated that synthesized lipid A derived from Alcaligenes faecalis (ALA) could enhance antigen-specific immunoglobulin (Ig) A and T helper (Th) 17 responses, when ALA was co-administered experimentally with an antigen as a vaccine adjuvant. This raised concerns about the safety of the ALA usage, since IgA and Th17 responses have been suggested to play a pathogenic role in several immune-mediated diseases, including multiple sclerosis (MS). We investigated whether ALA administrations could exacerbate an animal model of MS, Theiler’s murine encephalomyelitis virus (TMEV) infection. TMEV-infected SJL/J mice were administered ALA at various time points, and their neurological signs were observed for 7 weeks. We found that ALA administrations did not exacerbate TMEV-induced inflammatory disease or viral persistence in the central nervous system (CNS), clinically or histologically. Furthermore, ALA administrations did not enhance TMEV-specific humoral and cellular responses, including IgA and Th17 responses. On the other hand, principal component analysis (PCA) of the fecal, not the ileal, samples showed significant changes in the microbiota, characterized by increases in the relative abundance of bacteria belonging to the phylum Bacteroidota, including the genera Alistipes and Bacteroides. Therefore, ALA injections could be safe for use in immune-mediated diseases, whose immunopathology has been associated with IgA and Th17 responses. Full article

This systematic review article provides a comprehensive and critical analysis of the use of bioinputs in sustainable agriculture, focusing on biosurfactants and absorbent polymers, particularly bacterial cellulose. The article contextualises the growing challenges in agricultural production due to population growth, climate change, and environmental limitations, highlighting the need for alternatives to traditional synthetic inputs that exert negative environmental impacts. The article details functions, types, and benefits, emphasising the ability of bioinputs to improve soil fertility, increase the efficiency of nutrient use, enhance plant resistance to biotic and abiotic stress, and reduce the ecological footprint of agriculture. Emerging biotechnologies are discussed, such as the combined use of biosurfactants with natural polymers to ensure sustainability and efficiency. This article offers an updated description of recent scientific and technological evidence and addresses the potential and limitations of these biological inputs in the global context of modern agriculture. Full article

This review focuses on the research progress on natural products as β-lactam antibiotic adjuvants, aiming to address the escalating challenge of antibiotic resistance, particularly the inactivation of antibiotics caused by β-lactamases. The article provides an in-depth analysis of the mechanisms by which plant-derived (e.g., flavonoids, tannins, phenolics, terpenoids, and alkaloids) and microbial-derived (e.g., clavulanic acid, fungal metabolites, bacteriophages) natural products enhance antimicrobial efficacy. Key potentiation strategies discussed include efflux pump inhibition, membrane permeability alteration, biofilm disruption, PBP2a inhibition, and direct β-lactamase inhibition. Additionally, the review outlines in vitro methods (e.g., dilution and checkerboard assays) and in vivo models (e.g., mouse infection models) used to assess synergistic effects. It also addresses major challenges in identifying active compounds, elucidating mechanisms of action, and pharmacokinetic characterization. Looking forward, the article highlights the potential of multi-omics approaches, artificial intelligence, and nanotechnology to overcome existing bottlenecks, providing novel strategies for the development of effective and safe antibiotic adjuvants. These advances are expected to provide both theoretical insights and practical guidance for combating antibiotic-resistant bacterial infections. Full article

Background and purpose: The role of adjuvant radiation therapy (RT) in early-stage HER2-positive breast cancer treated with breast-conserving surgery (BCS) and systemic therapy remains uncertain in the era of HER2-targeted regimens. This study evaluates the survival impact of RT in patients aligned with the HERO RT de-escalation trial (NRG-BR008). Materials and methods: We queried the National Cancer Database for patients with early-stage HER2-positive invasive breast carcinoma treated with BCS and systemic therapy, stratified into HERO trial-aligned cohorts: Arm 1 (adjuvant systemic therapy) vs. Arm 2 (neoadjuvant systemic therapy, pathologic complete response). Within each cohort, patients receiving adjuvant RT were compared with those omitting RT. In the primary analysis, patients were propensity score matched (PSM) on demographics, diagnosis years, tumor characteristics, and trial stratification variables. Inverse probability of treatment weighting (IPTW) was additionally performed as a sensitivity analysis. Overall survival was evaluated using Kaplan–Meier, Cox regression, and restricted mean survival time (RMST). Results: In Arm 1 (818 patients, 94 deaths), 5-year OS was 96.9% with RT vs. 88.0% without RT, and 10-year OS was 94.3% vs. 68.5% (log-rank p < 0.001). RT omission was associated with higher mortality in the PSM Cox model (HR, 4.78; 95% CI, 2.84–8.02; p < 0.001), with an RMST advantage favoring RT of +2.86 months at 5 years and +12.55 months at 10 years (p < 0.001). In Arm 2 (176 patients, 10 deaths), 5-year OS was 97.6% with RT vs. 91.1% without RT, and OS at 107 months was 94.8% vs. 91.1% (log-rank p = 0.13). RT omission was not statistically significant in the PSM Cox model (HR, 3.40; 95% CI, 0.82–14.05; p = 0.09), though RMST favored RT (+1.83 months at 5 years, p = 0.004; +3.91 months at 107 months, p = 0.03). IPTW analyses were directionally consistent in Arm 1 (HR, 3.26; 95% CI, 2.52–4.21; p < 0.001) and inconclusive in Arm 2 (HR, 1.78; 95% CI, 0.80–3.95; p = 0.16). Conclusions: In this HERO-aligned national cohort, RT omission was associated with inferior OS in patients treated with adjuvant systemic therapy after BCS. Findings in the neoadjuvant pCR cohort were imprecise and hypothesis-generating. Given the retrospective registry design, lack of recurrence-specific endpoints, and potential residual confounding, results should not be interpreted as causal but support continued RT use outside prospective de-escalation trials. Full article

An increasing number of young women with hormone receptor-positive (HR+) early breast cancer desire pregnancy after treatment. Prolonged adjuvant endocrine therapy, concerns regarding recurrence risk, and treatment-related fertility decline have historically complicated reproductive decision-making in this population. This narrative review synthesizes current evidence on pregnancy after early HR+ breast cancer, with particular emphasis on prospective data from the POSITIVE trial. We examine the safety of temporary endocrine therapy interruption, the impact of assisted reproductive technologies (ART) in achieving pregnancy, breastfeeding feasibility and impact, hormonal predictors of fertility, pregnancy outcomes and considerations for special populations, including BRCA mutation carriers. Retrospective studies have suggested no adverse survival impact associated with pregnancy after breast cancer. The POSITIVE trial provides prospective evidence that temporary interruption of endocrine therapy to attempt pregnancy does not increase short-term recurrence risk in selected patients. Approximately three-quarters of participants achieved pregnancy. Fertility preservation and ART were commonly used and were not associated with worse short-term oncologic outcomes. Biomarkers such as anti-Müllerian hormone offer supportive but imperfect prediction of fertility potential. Breastfeeding was feasible for many women and did not adversely affect breast cancer outcomes. Available data among BRCA mutation carriers are reassuring but largely observational. Current evidence supports the safety and feasibility of pregnancy after early HR+ breast cancer in carefully selected patients. However, longer follow-up, inclusion of higher-risk populations, and evaluation of newer therapies are needed. Individualized, multidisciplinary counselling remains central to informed decision-making. Full article

Background/Objectives: Radiotherapy of the chest wall after mastectomy frequently leads to fibrosis, reduced tissue elasticity, erythema, pain and chronic skin-related symptoms that complicate reconstructive strategies. Autologous fat grafting has been proposed as a regenerative option for radiation induced soft tissue damage, but clinical data focused on patient-reported symptoms remain limited. The objective of this study was to describe symptomatic and clinical changes after autologous fat grafting in irradiated postmastectomy chest wall tissue. Methods: This pilot observational study included five female patients with a history of mastectomy followed by adjuvant chest wall radiotherapy. All patients underwent a single session of standard autologous fat grafting without adipose derived stem cell enrichment. Patient-reported symptoms, including pruritus, local discomfort, burning sensation and erythema, were recorded preoperatively and at six months using a standardized 0 to 5 scale. Scar pliability was assessed by two experienced physicians using the same scale. Only descriptive statistical analysis was performed. Results: All patients demonstrated lower postoperative symptom scores at six months. Mean reductions were observed for erythema (71.4 percent), burning sensation (61.1 percent) and pruritus (57.1 percent). Local discomfort decreased by 33.3 percent. Mean scar pliability scores increased from 2.2 to 3.2. No postoperative complications, such as infection, fat necrosis or oil cyst formation, were recorded. All patients completed the six month follow up. Conclusions: In this small pilot observational study, autologous fat grafting was well tolerated and associated with descriptive improvement of patient-reported symptoms and scar pliability in irradiated postmastectomy chest wall tissue. These findings suggest a potential symptomatic benefit of fat grafting, while larger studies with objective imaging and histological correlation are required to confirm efficacy and durability. Full article