Search Results (233)

Breast cancer (BC) is the most common malignancy and the second-leading cause of cancer-related mortalities in women. Epidemiological studies suggested the reduced BC incidence in Mediterranean populations due to the daily consumption of diets rich in extra-virgin olive oil (EVOO). EVOO secoiridoid phenolics are widely known for their positive outcomes on multiple cancers, including BC. The current study investigates the suppressive effects of individual and combined EVOO phenolics for BC progression and motility. Screening of a small library of EVOO phenolics at a single dose of 10 µM against the viability of the BC cell lines ZR-75-1 (luminal A) and MDA-MB-231 (triple negative BC, TNBC) identified oleocanthal (OC) and ligstroside aglycone (LA) as the most active hits. Screening of EVOO phenolics for BC cells migration inhibition identified OC, LA, and the EVOO lignans acetoxypinoresinol and pinoresinol as the most active hits. Combination studies of different olive phenolics showed that OC combined with LA had the best synergistic inhibitory effects against the TNBC MDA-MB-231 cells migration. A combination of 5 µM of each of OC and LA potently suppressed the migration and invasion of the MDA-MB-231 cells versus LA and OC individual therapies and vehicle control (VC). Animal studies using the ZR-75-1 BC cells orthotopic xenografting model in female nude mice showed significant tumor progression suppression by the combined OC-LA, 5 mg/kg each, ip, 3X/week treatments compared to individual LA and OC treatments and VC. The BC suppressive effects of the OC-LA combination were associated with the modulation of SMYD2–EZH2–STAT3 signaling pathway. A metastasis–clonogenicity animal study model using female nude mice subjected to tail vein injection of MDA-MB-231-Luc TNBC cells also revealed the effective synergy of the combined OC-LA, 5 mg/kg each, compared to their individual therapies and VC. Thus, EVOO cultivars rich in OC with optimal LA content can be useful nutraceuticals for invasive hormone-dependent BC and TNBC progression and metastasis. Full article

Neurodegenerative disorders, mental conditions, and cognitive decline represent significant challenges worldwide, with growing pieces of evidence implicating alterations in neurotrophin signaling as central to these diseases. Neurotrophins—such as nerve growth factor (NGF) and brain-derived neurotrophic factor (BDNF)—are indispensable for neuronal survival, differentiation, and synaptic plasticity, and their dysregulation is closely associated with various neuropathological situations. Similarly, dietary plant polyphenols, abundant in vegetables, fruits, wine, tea, and extra virgin olive oil, show powerful anti-inflammatory, antioxidant, and anti-apoptotic activities. This narrative review critically addresses the evolving body of evidence that links plant polyphenols and brain neurotrophins, emphasizing several molecular mechanisms by which polyphenols regulate and modulate neurotrophin signaling. Crucial pathways include mitigation of neuroinflammatory responses, activation of intracellular cascades such as the cAMP response element-binding protein (CREB), epigenetic modulation, and the diminution of oxidative stress. Together, these effects contribute to potentiated enhanced synaptic function, neuronal integrity, and better learning and memory processes. Moreover, this narrative review examines how polyphenol-induced upregulation of neurotrophins may alleviate conditions associated not only with neurodegeneration but also with addiction and mood disorders, suggesting extensive therapeutic approaches. Findings from clinical investigations and animal models are presented to sustain the neuroprotective role of polyphenol-rich diets. Lastly, future research directions are recommended, focusing on polyphenol bioavailability optimization, considering combinatory dietary stratagems, and proposing personalized nutritional interventions. This wide-ranging perspective highlights plant polyphenols as encouraging modulators of neurotrophin pathways and supports their inclusion in approaches aimed at promoting brain health and counteracting neurodegenerative decline. Full article

Background: Early defibrillation improves outcomes in cardiac arrest, but the optimal defibrillation strategy and energy requirements remain debated. This study investigated whether arterial blood gas (ABG) parameters could predict optimal defibrillation energy requirements for achieving the highest first-shock success rates in an animal model. Our study focused on clinical scenarios where ABG measurements are readily available, such as ventricular tachycardia and ventricular fibrillation storms requiring multiple shock deliveries. Materials and Methods: In the experimental setting, ventricular fibrillation was induced by 50 Hz direct current (DC), and the defibrillation threshold (DFT) was determined using a stepwise defibrillation protocol. ABG parameters were measured before each defibrillation attempt, recording partial arterial pressure of carbon dioxide (PaCO₂) and oxygen (PaO₂), pH, hematocrit (Hct), sodium (Na⁺), potassium (K⁺), and bicarbonate (HCO₃⁻) levels. The relationships between ABG parameters and the DFT were analyzed for 15 subjects using classical data analysis techniques and machine learning (ML) algorithms. Multiple ML models were trained and tested to predict the higher energy needed for successful defibrillation based on the ABG parameters. Results: Statistically significant differences were found in Hct and Na⁺ levels between the two DFT categories, above 130 Joules (J) and below 40 J (p < 0.01). The DFT negatively correlated with PaO₂ and positively correlated with Hct and Na⁺. However, other ABG parameters did not show significant correlations with DFT. Using ML, we predicted cases requiring higher defibrillation E. Our best-performing model, the Extra Trees Classifier, achieved 83% overall accuracy, with 100% and 67% precision rates for higher and lower DFT categories, respectively. We validated the model using bootstrap resampling and 10-fold cross-validation, confirming consistent performance. We identified Hct, PaCO₂, and PaO₂ as significant contributors to model prediction based on the feature importance value. Conclusions: Modern data analysis techniques applied to ABG parameters may guide personalized defibrillation energy selection, particularly in controlled clinical environments such as catheterization laboratories and intensive care units where ABG measurements are readily available. Full article

In the past 5 years, the COVID-19 pandemic has experienced frequently changing variants contextualizing immune evasion. The emergence of Omicron with >30–50 mutations on the spike gene has shown a sharp divergence from its relative VOCs, such as WT, Alpha, Beta, Gamma, and Delta. The requisition of prime boosting was essential within 3–6 months to improve the Nab response that had been not lasted for longer. Omicron subvariant BA.1.1 was less transmissible, but with an extra nine mutations in next variant BA.2 made it more transmissible. This remarkable heterogeneity was reported in ORF1ab or TRS sites, ORF7a, and 10 regions in the genomic sequences of Omicron BA.2 and its evolving subvariants BA.4.6, BF.7, BQ.2, BF. 7, BA.2.75.2, and BA.5 (BQ.1 and BQ.1.1). The mutational stability of subvariants XBB, XBB 1, XBB 1.5, and XBB 1.6 conferred a similar affinity towards ACE-2. This phenomenon has been reported in breakthrough infections and after booster vaccinations producing hybrid immunity. The reduced pathogenic nature of Omicron has implicated its adaptation either through immunocompromised individuals or other animal hosts. The binding capacity of RBD and ACE-2, including the proteolytic priming via TMPRSS2, reveals its (in-vitro) transmissibility behavior. RBD mutations signify transmissibility, S1/S2 enhances virulence, while S2 infers the effective immunogenic response. Initial mutations D614G, E484A, N501Y, Q493K, K417N, S477N, Y505H, and G496S were found to increase the Ab escape. Some mutations such as, R346K, L452R, and F486Vwere seen delivering immune pressure. HR2 region (S2) displayed mutations R436S, K444T, F486S, and D1199N with altered spike positions. Later on, the booster dose or breakthrough infections contributed to elevating the immune profile. Several other mutations in BA.1.1-N460K, R346T, K444T, and BA.2.75.2-F486S have also conferred the neutralization resistance. The least studied T-cell response in SARS-CoV-2 affects HLA- TCR interactions, thus, it plays a role in limiting the virus clearance. Antigenic cartographic analysis has also shown Omicron’s drift from its predecessor variants. The rapidly evolving SARS-CoV-2 variants and subvariants have driven the population-based immunity escape in fully immunized individuals within short period. This could be an indication that Omicron is heading towards endemicity and may evolve in future with subvariants could lead to outbreaks, which requires regular surveillance. Full article

Background/Objectives: The structural integrity and strength of the transgingival soft tissue seal around dental implant surfaces remain critical challenges. Therefore, animal models should include all three implant/tissue interfaces: bone, connective tissue, and epithelium. Thus, we sought to explore the rabbit mandibular diastema as a site for candidate intra-oral implant placement. Methods: Ninety-six custom mini-implants (with one of four different surfaces: machined, acid-etched, and with or without a nanotube coating) made from titanium 6/4 alloy were placed in the mandibular diastemas of twenty-four 16-week-old New Zealand white rabbits, with the implant collar above the alveolar crest. After 7, 21, and 42 days, the bony and connective tissue/implant interfaces were examined by light and scanning electron microscopy (SEM). Results: Of ninety-six implants, eight implants were found exposed to the oral cavity, with no evidence of soft tissue inflammation, suggesting that transmucosal implant placement would have been feasible. No significant differences were observed in collagen fiber orientation and fibrous tissue thickness by polarized light microscopy. However, SEM images showed that at all three time points, topographically complex nanotube surfaces had a profound effect on soft tissue peri-implant deposition, although functionally oriented collagen fibers were not identified attached to the implant surface. These surfaces also showed reparative peri-implant bone in the collar region. An intramembranous form of de novo bone formation was observed, together with tartrate-resistant acid-phosphatase-positive osteoclasts and multinucleate giant cells in the peri-implant endosseous compartment. Conclusions: Our results demonstrate that the rabbit mandibular diastema provides an intra-oral method of implant placement without the necessity of an extra-oral approach, tooth extractions, or bone augmentation procedures. Furthermore, given that three implant tissue interfaces can potentially be studied (bone, connective tissue, and epithelium) this model provides advantages over more traditional implant placement sites in the appendicular skeleton. Full article

Objective: To review recent advancements in cranial cruciate ligament disease (CCLD) in dogs, focusing on diagnostic innovations and treatment options. Study Design: Literature review. Animals or Sample Population: Not applicable. Methods: Analysis of current literature on diagnostic tools and treatment techniques for CCLD, with emphasis on recent trends and advancements. Results: Enhanced diagnostic tools, such as Computed Tomography (CT), offer detailed anatomical insights, improving the accuracy of CCLD assessments. Treatment approaches include extra-articular techniques like lateral fabellar suture stabilization, intra-articular methods with natural and synthetic implants, and advanced surgical procedures such as Tibial Plateau Leveling Osteotomy (TPLO), Tibial Tuberosity Advancement (TTA), and arthroscopy. Recent trends favor combining techniques, such as TPLO with lateral fabellar sutures or arthroscopy with TPLO, to optimize outcomes. Intra-articular techniques, while promising, may face challenges related to graft choice and tunnel placement. Conclusions: A multifaceted approach integrating advanced diagnostics and tailored treatments enhances patient outcomes for CCLD. Ongoing advancements in both diagnostic and therapeutic strategies are crucial for effective management. Clinical Significance/Impact: This review highlights recent advancements and research in diagnostic and therapeutic strategies for CCLD, providing valuable insights for veterinary surgeons and researchers. The integration of these advanced approaches is essential for improving clinical outcomes in canine CCLD management. Full article

Pathogenic Escherichia coli can cause a variety of intestinal and extra-intestinal infections in humans and animals. The availability and subsequent misuse of antimicrobials, especially in poultry production systems, has contributed immensely to the emergence and spread of multidrug-resistant E. coli. This study investigated the genotypic characterization of colistin-resistant E. coli and selected antimicrobial-resistance encoding genes along with their phenotypic resistant pattern and the multiple antimicrobial resistant (MAR) index from village chickens in Kelantan. Sixty E. coli isolates obtained from a previous study’s stock culture were enriched and analyzed using routine microbiological methods: Kirby–Bauer disc diffusion method, minimum inhibitory concentration (MIC), and PCR amplification of E. coli species-specific and multidrug-resistance mcr-positive E. coli. All the isolates were confirmed as E. coli and 16.6% (10/60) were positive for mcr. Five isolates were positive for mcr-1, three for mcr-4, and two for mcr-9. The mcr-positive isolates showed varying degrees of resistance to different antimicrobials. The isolates were resistant to gentamicin (100%), chloramphenicol (100%), and tetracycline (89.4%) and susceptible to ceftaxidime (2.26%) and imipenem (18%). Furthermore, 100%, 94.7%, and 89.4% of isolates from village chickens belonged to phylogroup C, B2, and E, while 21.0% and 42.1% of the isolates belonged to phylogroup A and B1, respectively. Sequence types (STs) of selected E. coli isolates were further analyzed using multi-locus sequence typing, and 10 different STs were identified. This study showed the emerging threats of multidrug-resistant mcr-positive E. coli gene in village chickens that are believed to be raised with minimal or no antibiotics. Full article

The Blastocystis sp. is a common enteric parasite found in humans and various animals. Blastocystis spp. infections may be asymptomatic or symptomatic, with gastrointestinal and extra-intestinal symptoms, such as diarrhea, nausea, abdominal pain, bloating, vomiting, or anorexia. The disease leading to symptoms is usually observed in participants with immune deficiency. We report the case of weight loss and diarrhea in a Blastocystis sp. infection in a 64-year-old renal transplant recipient. Full article

The development of gadolinium-based magnetic resonance imaging (MRI) contrast agents (CAs) is a highly challenging and demanding research field in metal-coordination medicinal chemistry. The recognized high capacity of hydroxypyridinone (HOPO)-based compounds to coordinate Gd (III) led us to evaluate the set of physic–chemical–biological properties of a new Gd (III) complex with a hexadentate tripodal ligand (H₃L) containing three 3,4-HOPO chelating moieties attached to an anchoring cyclohexane backbone. In particular, the thermodynamic stability constants of the complex were evaluated by potentiometry, showing the formation of a highly stable (1:1) Gd-L complex (log β_GdL = 26.59), with full coordination even in an acid-neutral pH under the experimental conditions used. Molecular simulations of the Gd (III) complex revealed a minimum energy structure with somewhat-distorted octahedral geometry, involving full metal hexa-coordination by the three bidentate moieties of the ligand arms, indicating that an extra water molecule should be coordinated to the metal ion, an important feature for the CAs (and the required enhancement of water proton relaxivity). In vivo biodistribution studies with the ⁶⁷Ga complex, as a surrogate of the corresponding Gd complex, showed in vivo stability and rapid excretion from the animal body. Though deserving further investigation, these results may give an input on future perspectives towards new MRI diagnostic agents. Full article

Background/Objectives: During the last decade, there has been an increased interest in phenolic compound-rich natural products as natural therapies for regulating the molecular pathways behind central obesity and associated metabolic disorders. The present scoping review presents the outcomes of clinical and preclinical studies examining the anti-obesity effects of high phenolic extra virgin olive oil (HP-EVOO) and its possible underlying molecular mechanisms. Methods: Studies published between 2014 and 2024 were searched via MEDLINE, Scopus, Cochrane, the Web of Science, Semantic Scholar, Google Scholar, Science.gov, and Clinicaltrials.gov databases. A combination of keywords and Boolean logic was used to search throughout the last decade in all databases, including “hyperglycemia” or “hypertension” or “metabolic syndrome” or “dyslipidemia” or “hyperlipidemia” or “hypoglycemia” or “obesity” or “macrovascular diabetic complications” or “microvascular diabetic complications” or “cardiovascular disease” or “overweight” or “insulin sensitivity” or “insulin resistance” and “extra virgin olive oil” or “high phenolic olive oil” and “human” or “animal model”. Results: The 10-year literature survey identified 21 studies in both animal models and humans, indicating that HP-EVOO improves inflammation, glycemic control, oxidative stress and endothelial function, potentially protecting against metabolic syndrome, hypertension and type 2 diabetes, even compared to EVOO. Moreover, HP-EVOO’s antiplatelet effect and improvement in HDL functionality reduce cardiovascular risk. Conclusions: The evidence presented in this study demonstrates that HP-EVOO represents an effective preventive and therapeutic dietary approach to cardiometabolic diseases. Full article

E. coli pathotypes, which cause extra-intestinal infections, pose significant public health challenges, emphasizing the need for virulence gene surveillance to understand their dynamics. Key virulence genes have been identified in E. coli from Andean community countries, predominantly linked to human and animal sources. However, detailed data on virulence profiles from environmental and food sources remain limited. This study utilized an in silico approach to analyze 2402 whole-genome sequences from EnteroBase, known for associations with antimicrobial resistance genes. Of the isolates, 30% were classified as ExPEC, averaging 39 virulence genes per isolate, with adhesin-related genes being the most predominant. These findings were consistent across human, environmental, animal, and food samples. Human and animal isolates exhibited greater diversity in adhesin, secreted factors, and toxin genes compared to other sources, whereas food samples contained the fewest factors. ST449 isolates exhibited an average of 50 virulence genes per genome, with secreted factors and adhesins equally represented, while ST131, ST38, and ST10 carried around 40 genes, predominantly adhesins. Overall, the diversity and frequency of virulence genes exceeded prior reports in the region, highlighting the importance of monitoring these traits to identify emerging patterns in pathogenic E. coli strains frequently subjected to antibiotic exposure. Full article

Data from post-mortem inspections conducted using official controls on the meat production of slaughtered pigs are generally considered valuable for identifying herd health issues and ensuring meat safety. However, several studies highlighted that a multi-stage assessment of lung changes would provide more useful information on animal health than the implemented binary (yes/no) recording. For this purpose, a new scheme was developed and subsequently used by trained official veterinarians at four slaughterhouses in Austria. Implementation of the multi-stage assessment was carried out in parallel with the conventional assessment, and data collected from both schemes were analyzed and compared to evaluate effectiveness. The analysis of the data (n = 20,345) showed that the most common alteration was low-grade (28.4%), followed by moderate-grade (11.3%,) and then high-grade pneumonia (5.2%). In the case of pleurisy, 88.9% of the carcasses showed no alterations of the pleura, and 11.1% had pathological changes (low-grade pleurisy = 4.7%, moderate-grade pleurisy = 2.7%, high-grade pleurisy = 3.7%). Analysis of the results showed a strong heterogeneity of the frequency of alterations between the batches reflecting various underlying animal health issues. Among the influencing factors, the origin of the pigs had the greatest influence. The project demonstrated that the new evaluation can be carried out easily with no extra time effort once staff are trained and the technological platform for reporting is adapted. The more detailed information ensures more useful feedback is provided to the farmers and supervising veterinarians, thereby ensuing animal welfare and contributing to sustainable, improved animal husbandry. Full article

Background: The clinical profiles of MNDs are dominated by inexorable motor decline, but subclinical proprioceptive, nociceptive and somatosensory deficits may also exacerbate mobility, dexterity, and bulbar function. While extra-motor pathology and frontotemporal involvement are widely recognised in motor neuron diseases (MNDs), reports of sensory involvement are conflicting. The potential contribution of sensory deficits to clinical disability is not firmly established and the spectrum of sensory manifestations is poorly characterised. Methods: A systematic review was conducted to examine the clinical, neuroimaging, electrophysiology and neuropathology evidence for sensory dysfunction in MND phenotypes. Results: In ALS, paraesthesia, pain, proprioceptive deficits and taste alterations are sporadically reported and there is also compelling electrophysiological, histological and imaging evidence of sensory network alterations. Gait impairment, impaired dexterity, and poor balance in ALS are likely to be multifactorial, with extrapyramidal, cerebellar, proprioceptive and vestibular deficits at play. Human imaging studies and animal models also confirm dorsal column-medial lemniscus pathway involvement as part of the disease process. Sensory symptoms are relatively common in spinal and bulbar muscular atrophy (SBMA) and Hereditary Spastic Paraplegia (HSP), but are inconsistently reported in primary lateral sclerosis (PLS) and in post-poliomyelitis syndrome (PPS). Conclusions: Establishing the prevalence and nature of sensory dysfunction across the spectrum of MNDs has a dual clinical and academic relevance. From a clinical perspective, subtle sensory deficits are likely to impact the disability profile and care needs of patients with MND. From an academic standpoint, sensory networks may be ideally suited to evaluate propagation patterns and the involvement of subcortical grey matter structures. Our review suggests that sensory dysfunction is an important albeit under-recognised facet of MND. Full article

Fusarium verticillioides can systematically infect maize through seeds, triggering stalk rot and ear rot at a later stage, thus resulting in yield loss and quality decline. Seeds carrying F. verticillioides are unsuitable for storage and pose a serious threat to human and animal health due to the toxins released by the fungus. Previously, the candidate gene ZmC2GnT was identified, using linkage and association analysis, as potentially implicated in maize seed resistance to F. verticillioides; however, its disease resistance mechanism remained unknown. Our current study revealed that ZmC2GnT codes an N-acetylglucosaminyltransferase, using sequence structure and evolutionary analysis. The candidate gene association analysis revealed multiple SNPs located in the UTRs and introns of ZmC2GnT. Cloning and comparing ZmC2GnT showed variations in the promoter and CDS of resistant and susceptible materials. The promoter of ZmC2GnT in the resistant parent contains one extra cis-element ABRE associated with the ABA signal, compared to the susceptible parent. Moreover, the amino acid sequence of ZmC2GnT in the resistant parent matches that of B73, but the susceptible parent contains ten amino acid alterations. The resistant material BT-1 and the susceptible material N6 were used as parents to observe the expression level of the ZmC2GnT. The results revealed that the expression of ZmC2GnT in disease-resistant maize seeds was significantly up-regulated after infection with F. verticillioides. After treatment with F. verticillioides or ABA, the expression activity of the ZmC2GnT promoter increased significantly in the resistant material, but no discernible difference was detected in the susceptible material. When ZmC2GnT from resistant and susceptible materials was overexpressed in Arabidopsis thaliana, the seeds’ resistance to F. verticillioides increased, although there was no significant difference between the two types of overexpressed plants. Our study revealed that ZmC2GnT could participate in the immune process of plants against pathogenic fungus. ZmC2GnT plays a significant role in regulating the disease-resistance process of maize seeds, laying the foundation for future research into the regulatory mechanism and the development of new disease-resistant maize varieties. Full article

Non-typhoidal Salmonella (NTS) infection poses a significant public health challenge globally, particularly in developing countries like India. NTS, predominantly represented by S. enterica serovars, is a major cause of intestinal and extra-intestinal infections. This review provides a comprehensive overview of longitudinal analyses of the prevalence of NTS in different regions of India encountered in the last 20 years and their antimicrobial resistance patterns. We followed several research investigations published during 2000–2024 to examine the incidence and prevalence of different serovars of NTS in several parts of India and followed published articles on NTS showing resistance to different antibiotics. We pointed out NTS serovars, which are predominantly isolated in various human and non-human sources, as observed in several investigations conducted in different regions of India. Our analysis revealed that, among serovars detected from various sources, S. Typhimurium is the most predominant one occurring across both human and non-human sources, followed by S. Enteritidis and S. Weltevreden. The occurrence of similar serovars of Salmonella in both human and non-human sources may be due to zoonotic transmission between animals and humans. Extensive research conducted across many geographic locations reveals that NTS isolates exhibit resistance to several antibiotics, with multidrug-resistance (MDR) being more common. These MDR strains basically show resistance to three or more classes of antibiotics, including critically important antimicrobials such as nalidixic acid, ciprofloxacin, and third-generation cephalosporins. Temporal trends suggest an alarming increase in resistance to these antibiotics, particularly in serovars such as S. Typhimurium and S. Enteritidis. Overall, the current article sheds light on the urgent need for surveillance, judicious antibiotic use, and the development of alternative treatment strategies to combat the rising tide of antibiotic-resistant NTS strains. Full article