Search Results (1,756)

The objective of this study was to evaluate the changes in enzymic activity, metabolites, and hematological responses during the first 56-d of arrival of newly received calves, which were qualified at reception as high-risk but diagnosed as clinically healthy. A total of 320 blood samples were taken from 64 crossbred bull calves (average initial body weight = 148.3 ± 1.3 kg) at different times from arrival (d 0, 14, 28, 42, and 56 of received). Calves included in the study were received in June (n = 20), November (n = 24), and April (n = 20); thus, experimental treatments were arranged in a generalized complete block design (three blocks = month of arrival). The following parameters were determined: total white blood cells (WBC): lymphocytes (LYM), lymphocytes % (LYM%), monocytes (MON), monocytes % (MON%), granulocytes (GRA), granulocytes % (GRA%), platelets (PLT), and mean platelet volume (MPV); red blood cells (RBC): red blood cell distribution width test % (RDW%), hematocrit (HCT), and mean corpuscular volume (MCV); hemoglobin (HGB): mean corpuscular hemoglobin (MCH) and mean corpuscular hemoglobin concentration (MCHC). The enzymatic activity and metabolites analyzed were alkaline phosphatase (ALP), gamma glutamyltransferase (GGT), aspartate aminotransferase (AST), alanine aminotransferase (ALT), total protein (TP), albumin (ALB), globulin (GLO), ALB/GLO ratio, blood urea nitrogen (BUN), creatinine (CRE), total bilirubin (TBIL), total cholesterol (TCHO), triglycerides (TG); (4) calcium (Ca), glucose (GLU), sodium (Na⁺), potassium (K⁺), and chlorine (Cl⁻). It was observed that ALP, ALT, TP, ALB, GLO, ALB/GLO ratio, TCHO, TG, Ca, and GLU increased as days from reception increased (linear effect, p ≤ 0.04), whereas CRE and TBIL were reduced (linear effect, p ≤ 0.02). A quadratic response (p ≤ 0.001) was observed to GGT and AST values being maximal on days 1 and 56 after arrival (p ≤ 0.001). Na⁺, K⁺, and Cl⁻ concentrations were not affected by prolonged days after arrival. Finally, blood cells of LYM, LYM%, PLT, RBC, HGB, HCT%, MCV, and MCH increased (linear effect, p ≤ 0.001) as the number of days after arrival increased. Whereas MON% was linearly decreased (p ≤ 0.05). It was concluded that even when all parameters were within the range of reference intervals (RIs) determined for healthy cattle, during the period of monitoring, as the days after arrival lengthened, blood serum parameters related to health and immunity increased, and metabolites related to tissue injury decreased. In contrast, plasmatic electrolytes (Na⁺, K⁺, and Cl⁻) were slightly reduced as the day after arrival increased. Apparently, at least 42 d is the minimum period after arrival to permit calves to reach more adequate physiological and metabolic conditions before starting the fattening phase. Full article

Prorocentrum, a dinoflagellate responsible for producing diarrhetic shellfish poisoning (DSP) toxins, poses significant threats to marine ecosystems, aquaculture industries, and human health. DSP toxins, including okadaic acid (OA), dinophysis toxin (DTX), and their diverse derivatives, continue to be identified and characterized. In this study, we report the isolation of four new diol esters of OA/DTX-1 from large-scale cultures of Prorocentrum lima. Their chemical structures were elucidated through comprehensive NMR and MS analyses, along with structural comparisons with the well-known OA. Notably, compound 1 featured an additional ester group within the diol unit, while compound 2 was revealed to be a C11 diol ester. The cytotoxicity of these newly isolated derivatives was evaluated against three cell lines: Neuro2a (mouse), HCT116 (human), and HepG2 (human). All diol esters exhibited cytotoxic effects, with compound 3 displaying toxicity comparable to OA. These results expand our understanding of DSP toxin diversity and provide valuable insight into the structural variations and biological activity of diol esters of OA/DTX-1. Full article

Background: Increasing evidence shows that Fusobacterium nucleatum (F. nucleatum) largely affects colorectal cancer (CRC) growth and progression; therefore, the inhibition of intratumoral F. nucleatum may be one realistic approach to combat CRC. Although antibiotics are helpful in eliminating bacteria, the major problem remains the rise of potential antibiotic-resistant strains and antibiotic-associated adverse effects. Currently, bacteriophage therapy has gained interest because of its high selectivity to bacterial hosts and may become a realistic approach in treating bacteria-associated cancers. Methods: In this study, a new F. nucleatum bacteriophage, ØTCUFN3, was isolated and its biological characteristics were identified. In vitro and in vivo studies were performed to investigate the effect of ØTCUFN3 in combating F. nucleatum-induced CRC growth. Results: By applying ØTCUFN3 to F. nucleatum-induced CRC cell lines, p53^+/+, and p53^−/− isogenic HCT116 cells, our results revealed an inhibition of CRC proliferation and the expression of epithelial-to-mesenchymal transition (EMT) markers. ØTCUFN3 injection also reduced the growth of F. nucleatum-induced mouse xenografts. Conclusions: Our results demonstrated the use of F. nucleatum bacteriophage against CRC, laying the foundation for the future usage of bacteriophage in cancer treatment. Full article

Colorectal cancer is one of the most common cancers worldwide and has a high mortality rate. In this study, we investigated the cytotoxic, proapoptotic, and anti-invasive effects of the synthetic indole phytoalexin MB-653. The antiproliferative effect was determined using an MTT assay, showing IC₅₀ values of 5.8 ± 0.3 μmol/L for HCT116 cells and 6.1 ± 2.1 μmol/L for Caco2 cells. Flow cytometry and Western blot analysis were employed to investigate the molecular mechanisms underlying cytotoxicity, proapoptotic action, and anti-invasion effects. The proapoptotic activity was evidenced by the activation of caspases 3 and 7, mitochondrial dysfunction, and an increased number of apoptotic cells, confirmed by annexin V/PI and AO/PI staining. Additionally, MB-653 induces dose-dependent G2/M phase cell cycle arrest, the cause of which could be cyclin B1/CDC2 complex dysfunction and/or a decrease in α-tubulin protein expression. Another important observation was that MB-653 modulated several signalling pathways associated with various cellular activities, including survival, proliferation, tumour invasiveness, metastasis, and epithelial–mesenchymal transition (EMT). We further demonstrated its safety for topical and parenteral application. To sum up, our results indicate the real potential of MB-653 in treating colorectal cancer. Full article

Background: Depression often coexists with anemia, potentially sharing common pathways, highlighting the need for treatments addressing both conditions simultaneously. This study evaluated the effect of probiotics on red blood cell (RBC) parameters in adults with depressive disorder. We hypothesized that probiotics would positively influence RBC parameters, potentially modulated by baseline inflammation or dietary intake, with improved RBC function correlating with better antidepressant outcomes. Methods: This secondary analysis of a two-arm, randomized, double-blind, controlled trial involved 116 adults with depressive disorder. Participants received a probiotic formulation containing Lactobacillus helveticus Rosell^®-52 and Bifidobacterium longum Rosell^®-175 or a placebo for 60 days. Data from 97 subjects were analyzed for RBC parameters, including hemoglobin (HGB), RBC count, hematocrit (HCT), mean corpuscular volume (MCV), mean hemoglobin concentration (MCH), mean corpuscular hemoglobin concentration (MCHC), and RBC distribution width (RDW). Results: Probiotic supplementation did not result in significant changes in RBC parameters compared to the placebo. However, probiotics may help stabilize HGB, HCT, MCH, and MCHC levels, potentially preventing fluctuations observed in the placebo group. Conclusions: While probiotics showed potential benefits for depressive symptoms, significant changes in RBC parameters were not observed. Larger studies are needed to clarify the mechanisms and clinical implications. Full article

Epidemiological studies suggest an increased risk of colorectal cancer (CRC) aggravation in patients with chronic kidney disease (CKD). Our previous study demonstrated that indoxyl sulfate, a uremic toxin whose concentration increases with CKD progression, exacerbates CRC through activation of the AhR and Akt pathways. Consequently, indoxyl sulfate has been proposed to be a significant link between CKD progression and CRC aggravation. The present study aimed to investigate the roles of c-Myc and β-Catenin, which are hypothesized to be downstream factors of indoxyl sulfate-induced AhR and Akt activation, in CRC cell proliferation and EGF sensitivity in HCT-116 CRC cells. Indoxyl sulfate significantly induced CRC cell proliferation at concentrations exceeding 62.5 µM, a process suppressed by the c-Myc inhibitor 10058-F4. Indoxyl sulfate activated the Akt/β-Catenin/c-Myc pathway as evidenced by the Akt inhibitor MK2206, which decreased both β-Catenin and c-Myc protein levels, and the β-Catenin inhibitor XAV-939, which reduced c-Myc protein levels. The AhR antagonist CH223191 also inhibited c-Myc upregulation, indicating involvement of the AhR/c-Myc pathway. MK2206 partially attenuated the indoxyl sulfate-induced AhR transcriptional activity, suggesting that Akt activation influences the AhR/c-Myc pathway. MK2206, CH223191, and 10058-F4 suppressed the increase in EGFR protein levels induced by indoxyl sulfate, indicating that the Akt/β-Catenin/c-Myc and AhR/c-Myc pathways enhance the sensitivity of HCT-116 CRC cells to EGF. These findings indicate that the elevation of indoxyl sulfate levels in the blood, due to CKD progression, could worsen CRC by promoting the proliferation of CRC cells and enhancing EGF signaling. Therefore, indoxyl sulfate could potentially serve as a therapeutic target for CRC aggravation in patients with CKD. Full article

Background/Objectives: Colorectal cancer (CRC) remains a major global health burden, necessitating innovative preventive approaches. Artemisia annua (A. annua), known for its extensive pharmacological properties, has shown potential in cancer therapy. This study investigates the chemopreventive efficacy of methanolic extract of A. annua (MEA) in an azoxymethane (AOM)-induced murine model of CRC, with a focus on its antioxidant, biomarker modulation, and pro-apoptotic activities. Methods: MEA was obtained via cold solvent extraction, yielding 39%, and demonstrated potent in vitro cytotoxicity against HCT116 and RKO colon cancer cell lines, with IC50 values of 20 µg/mL and 15 µg/mL, respectively. Swiss albino mice were treated with MEA beginning two weeks before AOM induction, with treatment continuing for 21 weeks. Survival was monitored for 40 weeks. Key outcomes included serum biomarker levels (ADA, GGT, CD73, LDH), antioxidant enzyme activities (SOD, CAT, GPx1, MDA), reactive oxygen species (ROS) modulation, apoptosis induction, and histopathological evaluation. Results: MEA significantly improved survival rates, reduced AOM-induced weight loss, and modulated cancer biomarkers, with marked reductions in ADA, GGT, CD73, and LDH levels. Antioxidant defenses were restored, as evidenced by increased SOD, CAT, and GPx1 activities and decreased MDA levels. ROS levels were significantly reduced, and apoptosis in colonic cells was effectively induced. Histopathological analysis revealed substantial mitigation of CRC-associated morphological abnormalities. Conclusions: MEA exhibits robust chemopreventive properties, demonstrating its potential to reduce oxidative stress, modulate key biomarkers, and induce apoptosis in CRC. These findings position MEA as a promising natural candidate for CRC prevention and therapy, warranting further exploration for clinical application. Full article

Background/Objectives: Hematopoietic cell transplantation (HCT) is a curative treatment for various hematological diseases but can lead to complications which increase malnutrition risk, particularly in allogeneic transplantation patients. This study evaluates the nutritional status evolution of patients undergoing HCT during hospitalization and follow-up. Methods: This retrospective observational study included 365 patients, divided into two groups: 134 underwent allogeneic HCT, while 231 underwent autologous transplantation or CAR-T therapy. Nutritional status was evaluated using Body Mass Index (BMI), Malnutrition Universal Screening Tool (MUST), and Global Leadership Initiative on Malnutrition (GLIM) criteria at four-time points: hospital admission, discharge, two-week follow-up, and one-month follow-up. Non-relapse-related complications were assessed based on hospital readmissions and reports during follow-up visits. Results: Patients experienced significant nutritional deterioration, with decreases in Body Mass Index (BMI) (p < 0.001) and increases in Malnutrition Universal Screening Tool (MUST) (p < 0.001) and Global Leadership Initiative on Malnutrition (GLIM) scores (p < 0.001), particularly among allogeneic transplant recipients (p = 0.025). Severe malnutrition or high malnutrition risk at discharge correlated with increased hospital readmissions during the follow-up (p = 0.024). Conclusions: The observed decline in nutritional status and its associated complications highlight the necessity of multidisciplinary interventions, such as nutritional prehabilitation programs and nutritional support protocols, to enhance clinical outcomes and reduce complications in HCT patients. Full article

Background/Objectives: Clostridioides difficile is a Gram-positive, spore-forming enteric pathogen that causes intestinal disorders, including inflammation and diarrhea, primarily through toxin production. Standard treatment options for C. difficile infection (CDI) involve a limited selection of antibiotics that are not fully effective, leading to high recurrence rates. Vaccination presents a promising strategy for preventing both CDI and its recurrence. Cell wall protein 2 (Cwp2), a highly immunogenic and abundant surface-exposed C. difficile cell wall protein, plays an important role in the bacterium’s adherence in vitro. In this study, we aimed to analyze the homology and immunogenicity of Cwp2 and its protection efficacy as a vaccine candidate against CDI in mice. Methods: we conducted in silico analyses to assess the homology and immunogenicity of Cwp2, and we evaluated its potential as a vaccine candidate against CDI using a mouse model of immunization and infection. Results: Our in silico analyses predicted the immunogenic region (functional domain) of Cwp2 and revealed its high homology among various toxinotypes and ribotypes (R.T.s) or sequence types (S.T.s). Immunizations of mice with the Cwp2 functional domain (Cwp2_A) induced potent IgG/A antibody responses against Cwp2_A, protected mice from CDI, and reduced C. difficile spore and toxin levels in feces post-infection. Additionally, anti-Cwp2_A sera inhibited the binding of C. difficile vegetative cells to HCT8 cells. Conclusions: Our report demonstrates for the first time the potential of Cwp2_A as an effective vaccine candidate against CDI in mice. Full article

Green tea kombucha, produced using a green tea (Camellia sinensis) grown in Brazil, was characterized and its in vitro bioactive properties were evaluated. Overall, 92 phenolic compounds were identified (70.7% flavonoids, 25% phenolic acids, 2.2% lignans, and 1.1% other polyphenols), contributing to the observed high antioxidant capacity. The major phenolics identified were gallocatechin, catechin 5-O-gallate, and epicatechin. Green tea kombucha exhibited antibacterial activity against all tested bacteria, being more effective against Salmonella spp. In addition, green tea kombucha demonstrated antimalarial activity against both chloroquine-sensitive and chloroquine-resistant strains of Plasmodium falciparum, and antiproliferative activity against cancer cell lines A549, HCT8, HepG2, and HUVEC. Additionally, it presented antioxidant properties by effectively reducing the generation of reactive oxygen species (ROS) and provided protection to erythrocytes against AAPH-induced oxidative stress. Thus, green tea kombucha is abundant in antioxidants and possesses intriguing bioactive properties that can be investigated by both the food and pharmaceutical sectors. Full article

The water channel AQP3 is an aquaglyceroporin expressed in villus epithelial cells, and it plays a role in water transport across human colonic surface cells. Beyond water, AQP3 can mediate glycerol and H₂O₂ transport. Abnormal expression and function of AQP3 have been found in various diseases often characterized by altered cell growth and proliferation. Here, the beneficial effects of MOMAST^® have been evaluated. MOMAST^® is an antioxidant-patented natural phenolic complex obtained from olive wastewater (OWW) of the Coratina cultivar. Treatment of human colon HCT8 cells with MOMAST^® reduced cell viability. Confocal studies and Western Blotting analysis demonstrated that treatment with MOMAST^® significantly decreased the staining and the expression of AQP3. Importantly, functional studies revealed that the reduction of AQP3 abundance correlates with a significant decrease in glycerol and H₂O₂ uptake. Indeed, the H₂O₂ transport was partially but significantly reduced in the presence of MOMAST^® or DFP00173, a selective inhibitor of AQP3. In addition, the MOMAST^®-induced AQP3 decrease was associated with reduced epithelial-mesenchymal transition (EMT)-related proteins such as vimentin and β-catenin. Together, these findings propose MOMAST^® as a potential adjuvant in colon diseases associated with abnormal cell growth by targeting AQP3. Full article

In allogeneic hematopoietic cell transplantation (HCT), a minority of patients have access to a suitable human leukocyte antigen (HLA)-matched related donor (MRD). To fill this gap, matched unrelated donors (MUDs) are an increasingly selected donor source. Usage and outcomes after MUD HCT for Canada are not described. We investigated temporal trends in MUD compared to MRD HCT from 2000 to 2019 using data reported to the Cell Therapy and Transplant Canada (CTTC) Registry. Of 7571 first allogeneic HCTs between 2000 and 2019, the proportion of MUD HCTs rose from 35.1% to 56.3% in the early (2000–2009) and later (2010–2019) eras, respectively. Comparing the two donor sources, the 5-year overall survival (OS) after MUD HCT for patients with malignant diseases was inferior to MRD HCT in the early era (p < 0.001). However, in the later era, OS was comparable for the two donor sources (p = 0.969). For patients with non-malignant diseases, the 5-year OS after MUD HCT was inferior to MRD in the early era (p < 0.001), but in the later era, the 5-year OS was similar between the two donor sources (p = 0.209). Improvements in OS after MUD HCT were accompanied by corresponding reductions in the 2-year non-relapse mortality after MUD HCT. We conclude that MUDs are the most common donor source in Canada, and key clinical outcomes after MUD have improved over time. Full article

Background/Objectives: Haematopoietic stem cell transplantation (HCT) induces profound immunosuppression, significantly increasing susceptibility to severe infections. This review examines vaccinations’ necessity, timing, and efficacy post-HCT to reduce infection-related morbidity and mortality. It aims to provide a structured protocol aligned with international and national recommendations. Methods: A systematic review of current guidelines and studies was conducted to assess vaccination strategies in HCT recipients. The analysis included the timing of vaccine administration, factors influencing efficacy, and contraindications. Recommendations for pre- and post-transplant vaccination schedules were synthesised, specifically for graft-versus-host disease (GVHD), immunosuppressive therapy, and hypogammaglobulinemia. Results: Vaccination is essential as specific immunity is often lost after HCT. Inactivated vaccines are recommended to commence three months post-transplant, including influenza, COVID-19, and pneumococcal vaccines. Live attenuated vaccines remain contraindicated for at least two years post-transplant and in patients with ongoing GVHD or immunosuppressive therapy. Factors such as GVHD and immunosuppressive treatments significantly impact vaccine timing and efficacy. The review also underscores the importance of pre-transplant vaccinations and ensuring that patients’ close contacts are adequately immunised to reduce transmission risks. Conclusions: Implementing a structured vaccination protocol post-HCT is critical to improving patient outcomes. Timely and effective vaccination strategies can mitigate infection risks while addressing individual patient factors such as GVHD and immunosuppression. This review highlights the need for tailored vaccination approaches to optimize immune reconstitution in HCT recipients. Full article

Myeloid chimerism better reflects donor stem cell engraftment than whole-blood chimerism in assessing graft function following allogeneic hematopoietic stem cell transplant (HCT). We describe our experience with 130 patients aged younger than 18 years, treated with allogeneic HCT using bone marrow or PBSC from HLA-matched donors for non-malignant diseases, whose pre-transplant conditioning therapy included alemtuzumab and who were monitored with lineage-specific chimerism after transplant. At 6 years post-transplant, overall survival (OS) was 91.1% and event-free survival (EFS) was 81.5%, with no grade III-IV acute GvHD or chronic GVHD observed. Recipient T-cells did not contribute to graft loss. Mixed T-cell chimerism (MC) did not affect EFS, and there was no connection between T-cell chimerism and myeloid chimerism in patients with MC or graft loss. MC significantly correlated with virus infection; more children with MC were CMV seropositive than those with complete chimerism (CC). Additionally, MC was more common in patients with CMV viramia post-transplant. CD8 T-cell reconstitution was affected by viral reactivation, including CMV, with CD8 T-cell counts higher in the MC group than in the CC group. Mixed T-cell chimerism is due to autologous, virus-specific, predominantly CD8, T-cell expansion, and is protective and not deleterious to the recipient. Full article

Heavy metals enter river basins through industrial effluents, agricultural wastes, surface run-offs, and other human activities, negatively impacting aquatic and terrestrial life by bioaccumulating in the food chain. This problem is on a continuous rise in under-developed and developing countries, such as in Pakistan. Therefore, the current study was aimed to determine concentrations of heavy metals, essential trace elements, and macrominerals (Zn, Pb, Ni, Mn, Mg, Fe, Cu, Cr, Co, Cd, Ca, and As) in the water, sediments, and tissues (gills, liver, and muscles) of Bagarius bagarius and Bagre marinus in the Jhelum River, Pakistan. The hematological and biochemical profiles of these fish across two sampling sites (Jhelum Bridge Khushab, upstream, and Langarwala Pull—downstream) were also evaluated. Results showed greater bioaccumulation of heavy metals in fish downstream, correlating with higher concentrations of these metals in water and sediments downstream. In the case of B. marinus, the highest concentration observed was 16.59 mg/g (Ca), and the lowest concentration was 9.51 mg/g (Fe). In the case of B. bagarius, the highest concentration observed was 17.47 mg/g (Ca), and the lowest concentration was 7.95 mg/g (Mg). Increased activities of alkaline phosphatase (ALP), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) were observed downstream. Hematological changes included increased white blood cells (WBCs) and decreased red blood cells (RBCs), lymphocytes, hemoglobin (Hb), platelets (Plt), and hematocrit (Hct). A significant correlation was observed among heavy metals across the water, sediment, and different tissues of B. marinus and B. bagarius. Moreover, principal component analysis (PCA) for both species along both sampling sites illustrated the relationship between fish tissues and metals. The current study concluded that the fish accumulated a significantly higher concentration of heavy metals downstream, which might be linked with dumping of the domestic wastes and industrial and agricultural runoff, adversely affecting both fish and human health. Full article