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Poultry Science May 2024Bone plays a crucial role in poultry's health and production. However, during the selection and cage farming, there has been a decline in bone quality. As the...
Bone plays a crucial role in poultry's health and production. However, during the selection and cage farming, there has been a decline in bone quality. As the development of breeding theory, researchers find that it's possible to enhance bone quality through selective breeding.This study measure 8 humerus quality in 260 samples of the 350-day-old female duck. By descripting the basic characteristic traits, mechanical property traits we found that all the bone quality traits had a large variable coefficient, especially mechanical properties trait (20-70%), indicating that there was a large difference in bone health status among laying ducks. The phenotypic correlations showed a high correlation between weight and density, diameter and perimeter, breaking and toughness (r = 0.52-0.68). And then, we performed the Genome-wide association study (GWAS) to reveal the candidate genes of humerus quality in ducks. Seven candidate protein-coding genes were identified with perimeter trait, and 52 protein-coding genes were associated with toughness trait. We also analysed the candidate region and performed KEGG and GO analyse for 75 candidate genes. Furthermore, the expression analyse of the above candidate genes in different stage of humerus and different tissues were performed. Finally, AP2A2, SMAD3, SMNDC1, NFIA, EPHB2, PMEPA1, UNC5C, ESR1, VAV3, NFATC2 deserve further focus. The obtained results can contribute to new insight into bone quality and provide new genetic biomarkers for application in duck breeding programs.
PubMed: 38806002
DOI: 10.1016/j.psj.2024.103851 -
Poultry Science May 2024Sodium dehydroacetate (DHA-Na) is a fungicidal preservative widely used in food and animal feed. DHA-Na can induce coagulation disorders in rats and poultry by...
Sodium dehydroacetate (DHA-Na) is a fungicidal preservative widely used in food and animal feed. DHA-Na can induce coagulation disorders in rats and poultry by inhibiting carboxylation of vitamin K-dependent proteins; it can also impair bone development in zebrafish. However, the effects of DHA-Na on broiler chicken bones remain unknown. Here, we assessed whether DHA-Na impairs bone development in broiler chickens. We administered Suji yellow chickens with 200 to 800 mg/kg DHA-Na, 2 mg/kg vitamin K, or both for 2 mo. Bone metabolite-related serum indicators, tissue micromorphology, and relevant protein expression were monitored during the treatment period. We also assessed primary chicken osteoblast activity, differentiation, and bone metabolite-related proteins after treatment with DHA-Na, vitamin K, or both. The results demonstrated that DHA-Na reduced bone index values and serum and bone osteoblast differentiation marker levels but blocked bone vitamin K cycle. DHA-Na also increased serum osteoclast differentiation marker levels, as well as the bone ratio of receptor activator of nuclear factor kappa-Β ligand to osteoprotegerin ratio. Moreover, DHA-Na reduced bone trabecular number, thickness, and area and increased trabecular separation considerably. In general, compared with the control group, the DHA-Na group demonstrated impairments in osteoblast activity and differentiation, as well as in the vitamin K cycle. By contrast, vitamin K supplementation led to considerable attenuation of the DHA-Na-induced decrease in osteogenic marker levels, along with a considerable increase in serum bone absorption marker levels and restoration of DHA-Na-induced bone microstructure damage. Vitamin K also attenuated DHA-Na-induced impairment in osteoclasts. In conclusion, the results indicated that in broiler chickens, DHA-Na supplementation can damage bones by inhibiting osteoblast function and increasing osteoclast activity; this damage can be prevented through vitamin K supplementation.
PubMed: 38805999
DOI: 10.1016/j.psj.2024.103834 -
Pain Physician May 2024The knee joint is one of the most common diseases in elderly individuals. This is a progressive and debilitating condition. The purpose of knee osteoarthritis treatment...
BACKGROUND
The knee joint is one of the most common diseases in elderly individuals. This is a progressive and debilitating condition. The purpose of knee osteoarthritis treatment is to manage pain, increase mobility, and improve the quality of life.
OBJECTIVES
This study evaluated the therapeutic effect of radiofrequency thermocoagulation (RFTC) on the genicular nerves in patients with intractable pain due to knee osteoarthritis, as well as its effects on pain severity and magnetic resonance imaging (MRI) findings.
STUDY DESIGN
A prospective outcome study.
SETTING
The outpatient clinic of a single academic medical center.
METHODS
We conducted a prospective study. Fifty consecutive patients with intractable knee pain due to osteoarthritis were enrolled and underwent ultrasound (US)-guided RFTC of the genicular nerves (medial superior genicular nerve, medial inferior genicular nerve, and lateral superior genicular nerve). Pain severity was measured using the Numeric Rating Scale (NRS), and knee osteoarthritis-associated symptoms were evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC) at pretreatment and one, 3, and 6 months after RFTC treatment. We also analyzed the relationship between therapeutic outcomes and pain severity based on pre-treatment and knee MRI findings.
RESULTS
No dropouts were observed. The most significant reduction in knee symptoms associated with knee osteoarthritis was observed after one month of treatment; however, at 3 and 6 months, there was a rebound effect, leading to a decrease in therapeutic efficacy. Nonetheless, there was still a noticeable decrease in symptoms due to knee osteoarthritis compared to those prior to RFTC treatment. The effect of RFTC treatment was better when pre-treatment pain was relatively less severe, knee effusion was not severe, there were no meniscal tears in the middle or posterior zones, no bone marrow edema in the middle and posterior zones of the femur and tibia, and no severe cartilage defects in the posterior femur and middle and posterior tibia.
LIMITATIONS
We conducted our study without a control or a placebo group.
CONCLUSION
RFTC of the genicular nerve is a good therapeutic option for controlling intractable pain following knee osteoarthritis. In addition, we found that a lower level of pain prior to treatment, along with the absence or lesser degree of knee joint effusion, as well as an absence or less severe middle or posterior knee pathologies associated with knee osteoarthritis, can predict a more favorable therapeutic outcome.
Topics: Humans; Osteoarthritis, Knee; Prospective Studies; Radiofrequency Ablation; Aged; Male; Female; Middle Aged; Pain, Intractable; Knee Joint; Treatment Outcome; Pain Management; Pain Measurement; Magnetic Resonance Imaging
PubMed: 38805537
DOI: No ID Found -
Frontiers in Allergy 2024Basophils are the least common granulocytes, accounting for <1% of peripheral blood leukocytes. In the last 20 years, analytical tools for mouse basophils have been... (Review)
Review
Basophils are the least common granulocytes, accounting for <1% of peripheral blood leukocytes. In the last 20 years, analytical tools for mouse basophils have been developed, and we now recognize that basophils play critical roles in various immune reactions, including the development of allergic inflammation and protective immunity against parasites. Moreover, the combined use of flow cytometric analyses and knockout mice has uncovered several progenitor cells committed to basophils in mice. Recently, advancements in single-cell RNA sequencing (scRNA-seq) technologies have challenged the classical view of the differentiation of various hematopoietic cell lineages. This is also true for basophil differentiation, and studies using scRNA-seq analysis have provided novel insights into basophil differentiation, including the association of basophil differentiation with that of erythrocyte/megakaryocyte and the discovery of novel basophil progenitor cells in the mouse bone marrow. In this review, we summarize the recent findings of basophil ontogeny in both mice and humans, mainly focusing on studies using scRNA-seq analyses.
PubMed: 38803659
DOI: 10.3389/falgy.2024.1402841 -
Frontiers in Immunology 2024Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin...
INTRODUCTION
Atherosclerosis, a leading cause of global cardiovascular mortality, is characterized by chronic inflammation. Central to this process is the NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome, which significantly influences atherosclerotic progression. Recent research has identified that the olfactory receptor 2 (Olfr2) in vascular macrophages is instrumental in driving atherosclerosis through NLRP3- dependent IL-1 production.
METHODS
To investigate the effects of Corilagin, noted for its anti-inflammatory attributes, on atherosclerotic development and the Olfr2 signaling pathway, our study employed an atherosclerosis model in ApoE mice, fed a high-fat, high-cholesterol diet, alongside cellular models in Ana-1 cells and mouse bone marrow-derived macrophages, stimulated with lipopolysaccharides and oxidized low-density lipoprotein.
RESULTS
The vivo and vitro experiments indicated that Corilagin could effectively reduce serum lipid levels, alleviate aortic pathological changes, and decrease intimal lipid deposition. Additionally, as results showed, Corilagin was able to cut down expressions of molecules associated with the Olfr2 signaling pathway.
DISCUSSION
Our findings indicated that Corilagin effectively inhibited NLRP3 inflammasome activation, consequently diminishing inflammation, macrophage polarization, and pyroptosis in the mouse aorta and cellular models via the Olfr2 pathway. This suggests a novel therapeutic mechanism of Corilagin in the treatment of atherosclerosis.
Topics: Animals; Hydrolyzable Tannins; NLR Family, Pyrin Domain-Containing 3 Protein; Atherosclerosis; Mice; Signal Transduction; Inflammasomes; Glucosides; Macrophages; Male; Disease Models, Animal; Mice, Inbred C57BL; Mice, Knockout, ApoE
PubMed: 38803504
DOI: 10.3389/fimmu.2024.1364161 -
Frontiers in Immunology 2024Explore the efficacy and safety of donor-derived CLL-1 chimeric antigen receptor T-cell therapy (CAR-T) for relapsed/refractory acute myeloid leukemia (R/R AML) bridging...
Case report: Donor-derived CLL-1 chimeric antigen receptor T-cell therapy for relapsed/refractory acute myeloid leukemia bridging to allogeneic hematopoietic stem cell transplantation after remission.
BACKGROUND
Explore the efficacy and safety of donor-derived CLL-1 chimeric antigen receptor T-cell therapy (CAR-T) for relapsed/refractory acute myeloid leukemia (R/R AML) bridging to allogeneic hematopoietic stem cell transplantation (allo-HSCT) after remission.
CASE PRESENTATION
An adult R/R AML patient received an infusion of donor-derived CLL-1 CAR-T cells, and the conditioning regimen bridging to allo-HSCT was started immediately after remission on day 11 after CAR-T therapy upon transplantation. Then, routine post-HSCT monitoring of blood counts, bone marrow (BM) morphology, flow cytometry, graft-versus-host disease (GVHD) manifestations, and chimerism status were performed.
RESULT
After CAR-T therapy, cytokine release syndrome was grade 1. On day 11 after CAR-T therapy, the BM morphology reached complete remission (CR), and the conditioning regimen bridging to allo-HSCT started. Leukocyte engraftment, complete donor chimerism, and platelet engraftment were observed on days +18, +23, and +26 post-allo-HSCT, respectively. The BM morphology showed CR and flow cytometry turned negative on day +23. The patient is currently at 4 months post-allo-HSCT with BM morphology CR, negative flow cytometry, complete donor chimerism, and no extramedullary relapse/GVHD.
CONCLUSION
Donor-derived CLL-1 CAR-T is an effective and safe therapy for R/R AML, and immediate bridging to allo-HSCT after remission may better improve the long-term prognosis of R/R AML.
Topics: Humans; Hematopoietic Stem Cell Transplantation; Leukemia, Myeloid, Acute; Immunotherapy, Adoptive; Transplantation, Homologous; Male; Receptors, Chimeric Antigen; Remission Induction; Graft vs Host Disease; Middle Aged; Transplantation Conditioning; Adult; Treatment Outcome; Tissue Donors; Female
PubMed: 38803489
DOI: 10.3389/fimmu.2024.1389227 -
Frontiers in Pharmacology 2024This study aimed to conduct the first meta-analysis to comprehensively evaluate the clinical effectiveness and safety of Xiaochaihu Decoction in treating Cancer-related...
Exploring the therapeutic potential of "Xiaochaihu Decoction": a systematic review and meta-analysis on the clinical effectiveness and safety in managing cancer-related fever.
This study aimed to conduct the first meta-analysis to comprehensively evaluate the clinical effectiveness and safety of Xiaochaihu Decoction in treating Cancer-related Fever (CRF). Eight databases were systematically searched in September 2023. The risk of bias (ROB) 2.0 tool recommended by Cochrane Handbook was applied to evaluate the ROB of the included randomized controlled trials (RCTs). Additionally, the quality of evidence was assessed using the Grading of recommendations assessment, development and evaluation (GRADE) tool. We included 18 RCTs involving 1,424 patients. Compared to Western medicine or Xinhuang Tablets, Xiaochaihu Decoction significantly improved clinical effectiveness in CRF patients (risk ratio [RR] = 1.24, 95% confidence interval [CI]: 1.17, 1.32) and expedited the normalization of body temperature (mean difference [MD] = -5.29, 95%CI: -5.59, -4.99). It also demonstrated a reduction in tumor necrosis factor-α (TNF-α) levels (MD = -0.63, 95%CI: -0.84, -0.41) and an increase in IL-2 levels (MD = 1.42, 95%CI: -1.09, 1.74). Analysis of Karnofsky Performance Status (KPS) scores showed that the use of Xiaochaihu Decoction improved the quality of life in CRF patients (RR = 1.57, 95%CI: 1.11, 2.22) and reduced the incidence of adverse events. However, it is important to note that the majority of included studies showed "some concerns" in risk of bias based on ROB 2.0, and the evidence quality assessed by GRADE method was rated as "low". While this study suggests the clinical effectiveness and safety of Xiaochaihu Decoction in treating patients with CRF, confirming these findings will necessitate additional high-quality, large-scale RCTs in future research. https://www.crd.york.ac.uk/prospero/, identifier CRD42023484068.
PubMed: 38803432
DOI: 10.3389/fphar.2024.1359866 -
Journal of Translational Medicine May 2024A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their...
BACKGROUND
A former cohort study has raised concern regarding the unanticipated hazard of omeprazole in expediting osteoarthritis (OA) advancement. The precise nature of their causal evidence, however, remains undetermined. The present research endeavors to investigate the underlying causal link between omeprazole and OA through the application of mendelian randomization (MR) analysis.
METHODS
The study incorporated the ukb-a-106 and ukb-b-14,486 datasets. The investigation of causal effects employed methodologies such as MR-Egger, Weighted median, Inverse variance weighted (IVW) with multiplicative random effects, and IVW (fixed effects). The IVW approach was predominantly considered for result interpretation. Sensitivity analysis was conducted, encompassing assessments for heterogeneity, horizontal pleiotropy, and the Leave-one-out techniques.
RESULTS
The outcomes of the MR analysis indicated a causal relationship between omeprazole and OA, with omeprazole identified as a contributing risk factor for OA development (IVW model: OR = 1.2473, P < 0.01 in ukb-a-106; OR = 1.1288, P < 0.05 in ukb-b-14,486). The sensitivity analysis underscored the robustness and dependability of the above-mentioned analytical findings.
CONCLUSION
This study, employing MR, reveals that omeprazole, as an exposure factor, elevates the risk of OA. Considering the drug's efficacy and associated adverse events, clinical practitioners should exercise caution regarding prolonged omeprazole use, particularly in populations with heightened OA risks. Further robust and high-quality research is warranted to validate our findings and guide clinical practice.
Topics: Humans; Omeprazole; Mendelian Randomization Analysis; Osteoarthritis; United Kingdom; Biological Specimen Banks; Risk Factors; Female; Male; Middle Aged; UK Biobank
PubMed: 38802944
DOI: 10.1186/s12967-024-05255-y -
Cell Communication and Signaling : CCS May 2024Acute respiratory distress syndrome (ARDS) is a severe and fatal disease. Although mesenchymal stem cell (MSC)-based therapy has shown remarkable efficacy in treating...
BACKGROUND
Acute respiratory distress syndrome (ARDS) is a severe and fatal disease. Although mesenchymal stem cell (MSC)-based therapy has shown remarkable efficacy in treating ARDS in animal experiments, clinical outcomes have been unsatisfactory, which may be attributed to the influence of the lung microenvironment during MSC administration. Extracellular vesicles (EVs) derived from endothelial cells (EC-EVs) are important components of the lung microenvironment and play a crucial role in ARDS. However, the effect of EC-EVs on MSC therapy is still unclear. In this study, we established lipopolysaccharide (LPS) - induced acute lung injury model to evaluate the impact of EC-EVs on the reparative effects of bone marrow-derived MSC (BM-MSC) transplantation on lung injury and to unravel the underlying mechanisms.
METHODS
EVs were isolated from bronchoalveolar lavage fluid of mice with LPS - induced acute lung injury and patients with ARDS using ultracentrifugation. and the changes of EC-EVs were analysed using nanoflow cytometry analysis. In vitro assays were performed to establish the impact of EC-EVs on MSC functions, including cell viability and migration, while in vivo studies were performed to validate the therapeutic effect of EC-EVs on MSCs. RNA-Seq analysis, small interfering RNA (siRNA), and a recombinant lentivirus were used to investigate the underlying mechanisms.
RESULTS
Compared with that in non-ARDS patients, the quantity of EC-EVs in the lung microenvironment was significantly greater in patients with ARDS. EVs derived from lipopolysaccharide-stimulated endothelial cells (LPS-EVs) significantly decreased the viability and migration of BM-MSCs. Furthermore, engrafting BM-MSCs pretreated with LPS-EVs promoted the release of inflammatory cytokines and increased pulmonary microvascular permeability, aggravating lung injury. Mechanistically, LPS-EVs reduced the expression level of isocitrate dehydrogenase 2 (IDH2), which catalyses the formation of α-ketoglutarate (α-KG), an intermediate product of the tricarboxylic acid (TCA) cycle, in BM-MSCs. α-KG is a cofactor for ten-eleven translocation (TET) enzymes, which catalyse DNA hydroxymethylation in BM-MSCs.
CONCLUSIONS
This study revealed that EC-EVs in the lung microenvironment during ARDS can affect the therapeutic efficacy of BM-MSCs through the IDH2/TET pathway, providing potential strategies for improving the therapeutic efficacy of MSC-based therapy in the clinic.
Topics: Extracellular Vesicles; Animals; Mesenchymal Stem Cells; Respiratory Distress Syndrome; Endothelial Cells; Humans; Mice; Mesenchymal Stem Cell Transplantation; Isocitrate Dehydrogenase; Mice, Inbred C57BL; Male; Lipopolysaccharides; Signal Transduction; Acute Lung Injury; Cell Movement
PubMed: 38802896
DOI: 10.1186/s12964-024-01672-0 -
Journal of Cellular and Molecular... May 2024Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical...
Autophagy may play an important role in the occurrence and development of glucocorticoid-induced osteonecrosis of the femoral head (GC-ONFH). Lithium is a classical autophagy regulator, and lithium can also activate osteogenic pathways, making it a highly promising therapeutic agent for GC-ONFH. We aimed to evaluate the potential therapeutic effect of lithium on GC-ONFH. For in vitro experiments, primary osteoblasts of rats were used for investigating the underlying mechanism of lithium's protective effect on GC-induced autophagy levels and osteogenic activity dysfunction. For in vivo experiments, a rat model of GC-ONFH was used for evaluating the therapeutic effect of oral lithium on GC-ONFH and underlying mechanism. Findings demonstrated that GC over-activated the autophagy of osteoblasts and reduced their osteogenic activity. Lithium reduced the over-activated autophagy of GC-treated osteoblasts through PI3K/AKT/mTOR signalling pathway and increased their osteogenic activity. Oral lithium reduced the osteonecrosis rates in a rat model of GC-ONFH, and restrained the increased expression of autophagy related proteins in bone tissues through PI3K/AKT/mTOR signalling pathway. In conclusion, lithium can restrain over-activated autophagy by activating PI3K/AKT/mTOR signalling pathway and up-regulate the expression of genes for bone formation both in GC induced osteoblasts and in a rat model of GC-ONFH. Lithium may be a promising therapeutic agent for GC-ONFH. However, the role of autophagy in the pathogenesis of GC-ONFH remains controversial. Studies are still needed to further explore the role of autophagy in the pathogenesis of GC-ONFH, and the efficacy of lithium in the treatment of GC-ONFH and its underlying mechanisms.
Topics: Animals; Autophagy; Glucocorticoids; Rats; Femur Head Necrosis; TOR Serine-Threonine Kinases; Signal Transduction; Lithium; Osteoblasts; Male; Osteogenesis; Rats, Sprague-Dawley; Proto-Oncogene Proteins c-akt; Disease Models, Animal; Phosphatidylinositol 3-Kinases; Femur Head; Osteonecrosis
PubMed: 38801405
DOI: 10.1111/jcmm.18385