Hepatocellular carcinoma with Budd-Chiari syndrome due to membranous obstruction of the inferior vena cava with long-term follow-up: a case report

Membranous obstruction of the inferior vena cava (MOVC) is a rare subset of Budd-Chiari syndrome (BCS) with a subacute onset that is often complicated by cirrhosis and hepatocellular carcinoma (HCC). Here we report a case of recurrent HCC in a patient with cirrhosis and BCS that was treated with several episodes of transarterial chemoembolization followed by surgical tumorectomy, whereas the MOVC was successfully treated with balloon angioplasty followed by endovascular stenting. The patient was followed up for 9.9 years without anticoagulation and experienced no stent thrombosis. After the tumorectomy, the patient was HCC-free for 4.4 years of follow-up

Biogenesis and delivery of extracellular vesicles: harnessing the power of EVs for diagnostics and therapeutics

Extracellular vesicles (EVs) are membrane-enclosed particles secreted by a variety of cell types. These vesicles encapsulate a diverse range of molecules, including proteins, nucleic acids, lipids, metabolites, and even organelles derived from their parental cells. While EVs have emerged as crucial mediators of intercellular communication, they also hold immense potential as both biomarkers and therapeutic agents for numerous diseases. A thorough understanding of EV biogenesis is crucial for the development of EV-based diagnostic developments since the composition of EVs can reflect the health and disease status of the donor cell. Moreover, when EVs are taken up by target cells, they can exert profound effects on gene expression, signaling pathways, and cellular behavior, which makes these biomolecules enticing targets for therapeutic interventions. Yet, despite decades of research, the intricate processes underlying EV biogenesis by donor cells and subsequent uptake by recipient cells remain poorly understood. In this review, we aim to summarize current insights and advancements in the biogenesis and uptake mechanisms of EVs. By shedding light on the fundamental mechanisms governing EV biogenesis and delivery, this review underscores the potential of basic mechanistic research to pave the way for developing novel diagnostic strategies and therapeutic applications

Why Are Outcomes Different for Registry Patients Enrolled Prospectively and Retrospectively? Insights from the Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF).

Background: Retrospective and prospective observational studies are designed to reflect real-world evidence on clinical practice, but can yield conflicting results. The GARFIELD-AF Registry includes both methods of enrolment and allows analysis of differences in patient characteristics and outcomes that may result. Methods and Results: Patients with atrial fibrillation (AF) and ≥1 risk factor for stroke at diagnosis of AF were recruited either retrospectively (n = 5069) or prospectively (n = 5501) from 19 countries and then followed prospectively. The retrospectively enrolled cohort comprised patients with established AF (for a least 6, and up to 24 months before enrolment), who were identified retrospectively (and baseline and partial follow-up data were collected from the emedical records) and then followed prospectively between 0-18 months (such that the total time of follow-up was 24 months; data collection Dec-2009 and Oct-2010). In the prospectively enrolled cohort, patients with newly diagnosed AF (≤6 weeks after diagnosis) were recruited between Mar-2010 and Oct-2011 and were followed for 24 months after enrolment. Differences between the cohorts were observed in clinical characteristics, including type of AF, stroke prevention strategies, and event rates. More patients in the retrospectively identified cohort received vitamin K antagonists (62.1% vs. 53.2%) and fewer received non-vitamin K oral anticoagulants (1.8% vs . 4.2%). All-cause mortality rates per 100 person-years during the prospective follow-up (starting the first study visit up to 1 year) were significantly lower in the retrospective than prospectively identified cohort (3.04 [95% CI 2.51 to 3.67] vs . 4.05 [95% CI 3.53 to 4.63]; p = 0.016). Conclusions: Interpretations of data from registries that aim to evaluate the characteristics and outcomes of patients with AF must take account of differences in registry design and the impact of recall bias and survivorship bias that is incurred with retrospective enrolment. Clinical Trial Registration: - URL: http://www.clinicaltrials.gov . Unique identifier for GARFIELD-AF (NCT01090362)

Risk profiles and one-year outcomes of patients with newly diagnosed atrial fibrillation in India: Insights from the GARFIELD-AF Registry.

BACKGROUND: The Global Anticoagulant Registry in the FIELD-Atrial Fibrillation (GARFIELD-AF) is an ongoing prospective noninterventional registry, which is providing important information on the baseline characteristics, treatment patterns, and 1-year outcomes in patients with newly diagnosed non-valvular atrial fibrillation (NVAF). This report describes data from Indian patients recruited in this registry. METHODS AND RESULTS: A total of 52,014 patients with newly diagnosed AF were enrolled globally; of these, 1388 patients were recruited from 26 sites within India (2012-2016). In India, the mean age was 65.8 years at diagnosis of NVAF. Hypertension was the most prevalent risk factor for AF, present in 68.5% of patients from India and in 76.3% of patients globally (P < 0.001). Diabetes and coronary artery disease (CAD) were prevalent in 36.2% and 28.1% of patients as compared with global prevalence of 22.2% and 21.6%, respectively (P < 0.001 for both). Antiplatelet therapy was the most common antithrombotic treatment in India. With increasing stroke risk, however, patients were more likely to receive oral anticoagulant therapy [mainly vitamin K antagonist (VKA)], but average international normalized ratio (INR) was lower among Indian patients [median INR value 1.6 (interquartile range {IQR}: 1.3-2.3) versus 2.3 (IQR 1.8-2.8) (P < 0.001)]. Compared with other countries, patients from India had markedly higher rates of all-cause mortality [7.68 per 100 person-years (95% confidence interval 6.32-9.35) vs 4.34 (4.16-4.53), P < 0.0001], while rates of stroke/systemic embolism and major bleeding were lower after 1 year of follow-up. CONCLUSION: Compared to previously published registries from India, the GARFIELD-AF registry describes clinical profiles and outcomes in Indian patients with AF of a different etiology. The registry data show that compared to the rest of the world, Indian AF patients are younger in age and have more diabetes and CAD. Patients with a higher stroke risk are more likely to receive anticoagulation therapy with VKA but are underdosed compared with the global average in the GARFIELD-AF. CLINICAL TRIAL REGISTRATION-URL: http://www.clinicaltrials.gov. Unique identifier: NCT01090362

GWAS Reveals a Novel Candidate Gene <i>CmoAP2/ERF</i> in Pumpkin (<i>Cucurbita moschata</i>) Involved in Resistance to Powdery Mildew

Pumpkin (Cucurbita moschata Duchesne ex Poir.) is a multipurpose cash crop rich in antioxidants, minerals, and vitamins; the seeds are also a good source of quality oils. However, pumpkin is susceptible to the fungus Podosphaera xanthii, an obligate biotrophic pathogen, which usually causes powdery mildew (PM) on both sides of the leaves and reduces photosynthesis. The fruits of infected plants are often smaller than usual and unpalatable. This study identified a novel gene that involves PM resistance in pumpkins through a genome-wide association study (GWAS). The allelic variation identified in the CmoCh3G009850 gene encoding for AP2-like ethylene-responsive transcription factor (CmoAP2/ERF) was proven to be involved in PM resistance. Validation of the GWAS data revealed six single nucleotide polymorphism (SNP) variations in the CmoAP2/ERF coding sequence between the resistant (IT 274039 [PMR]) and the susceptible (IT 278592 [PMS]). A polymorphic marker (dCAPS) was developed based on the allelic diversity to differentiate these two haplotypes. Genetic analysis in the segregating population derived from PMS and PMR parents provided evidence for an incomplete dominant gene-mediated PM resistance. Further, the qRT-PCR assay validated the elevated expression of CmoAP2/ERF during PM infection in the PMR compared with PMS. These results highlighted the pivotal role of CmoAP2/ERF in conferring resistance to PM and identifies it as a valuable molecular entity for breeding resistant pumpkin cultivars

Selective removal of radioactive iodine from water using reusable Fe@Pt adsorbents

© 2022 The Author(s)Environmental damage from serious nuclear accidents should be urgently restored, which needs the removal of radioactive species. Radioactive iodine isotopes are particularly problematic for human health because they are released in large amounts and retain radioactivity for a substantial time. Herein, we prepare platinum-coated iron nanoparticles (Fe@Pt) as a highly selective and reusable adsorbent for iodine species, i.e., iodide (I−), iodine (I2), and methyl iodide (CH3I). Fe@Pt selectively separates iodine species from seawater and groundwater with a removal efficiency ≥ 99.8%. The maximum adsorption capacity for the iodine atom of all three iodine species was determined to be 25 mg/g. The magnetic properties of Fe@Pt allow for the facile recovery and reuse of Fe@Pt, which remains stable with high efficiency (97.5%) over 100 uses without structural and functional degradation in liquid media. Practical application to the removal of radioactive 129I and feasibility for scale-up using a 20 L system demonstrate that Fe@Pt can function as a reusable adsorbent for the selective removal of iodine species. This systematic procedure is a standard protocol for designing highly active adsorbents for the clean separation and removal of various chemical species dissolved in wastewater.11Nsciescopu

Selective removal of radioactive iodine from water using reusable Fe@Pt adsorbents

© 2022 The Author(s)Environmental damage from serious nuclear accidents should be urgently restored, which needs the removal of radioactive species. Radioactive iodine isotopes are particularly problematic for human health because they are released in large amounts and retain radioactivity for a substantial time. Herein, we prepare platinum-coated iron nanoparticles (Fe@Pt) as a highly selective and reusable adsorbent for iodine species, i.e., iodide (I−), iodine (I2), and methyl iodide (CH3I). Fe@Pt selectively separates iodine species from seawater and groundwater with a removal efficiency ≥ 99.8%. The maximum adsorption capacity for the iodine atom of all three iodine species was determined to be 25 mg/g. The magnetic properties of Fe@Pt allow for the facile recovery and reuse of Fe@Pt, which remains stable with high efficiency (97.5%) over 100 uses without structural and functional degradation in liquid media. Practical application to the removal of radioactive 129I and feasibility for scale-up using a 20 L system demonstrate that Fe@Pt can function as a reusable adsorbent for the selective removal of iodine species. This systematic procedure is a standard protocol for designing highly active adsorbents for the clean separation and removal of various chemical species dissolved in wastewater.N

Soluble Prokaryotic Overexpression and Purification of Human GM-CSF Using the Protein Disulfide Isomerase b′a′ Domain

Granulocyte-macrophage colony-stimulating factor (GM-CSF) is a member of the colony-stimulating factor (CSF) family, which functions to enhance the proliferation and differentiation of hematopoietic stem cells and other hematopoietic lineages such as neutrophils, dendritic cells, or macrophages. These proteins have thus generated considerable interest in clinical therapy research. A current obstacle to the prokaryotic production of human GM-CSF (hGM-CSF) is its low solubility when overexpressed and subsequent complex refolding processes. In our present study, the solubility of hGM-CSF was examined when combined with three N-terminal fusion tags in five E. coli strains at three different expression temperatures. In the five E. coli strains BL21 (DE3), ClearColi BL21 (DE3), LOBSTR, SHuffle T7 and Origami2 (DE3), the hexahistidine-tagged hGM-CSF showed the best expression but was insoluble in all cases at each examined temperature. Tagging with the maltose-binding protein (MBP) and the b′a′ domain of protein disulfide isomerase (PDIb′a′) greatly improved the soluble overexpression of hGM-CSF at 30 °C and 18 °C. The solubility was not improved using the Origami2 (DE3) and SHuffle T7 strains that have been engineered for disulfide bond formation. Two conventional chromatographic steps were used to purify hGM-CSF from the overexpressed PDIb′a′-hGM-CSF produced in ClearColi BL21 (DE3). In the experiment, 0.65 mg of hGM-CSF was isolated from a 0.5 L flask culture of these E. coli and showed a 98% purity by SDS-PAGE analysis and silver staining. The bioactivity of this purified hGM-CSF was measured at an EC50 of 16.4 ± 2 pM by a CCK8 assay in TF-1 human erythroleukemia cells

Vitamin C Activates Osteoblastogenesis and Inhibits Osteoclastogenesis via Wnt/β-Catenin/ATF4 Signaling Pathways

This study evaluated the effects of vitamin C on osteogenic differentiation and osteoclast formation, and the effects of vitamin C concentration on bone microstructure in ovariectomized (OVX) Wistar rats. Micro-computed tomography analysis revealed the recovery of bone mineral density and bone separation in OVX rats treated with vitamin C. Histomorphometrical analysis revealed improvements in the number of osteoblasts, osteoclasts, and osteocytes; the osteoblast and osteoclast surface per bone surface; and bone volume in vitamin C-treated OVX rats. The vitamin C-treated group additionally displayed an increase in the expression of osteoblast differentiation genes, including bone morphogenetic protein-2, small mothers against decapentaplegic 1/5/8, runt-related transcription factor 2, osteocalcin, and type I collagen. Vitamin C reduced the expression of osteoclast differentiation genes, such as receptor activator of nuclear factor kappa-B, receptor activator of nuclear factor kappa-B ligand, tartrate-resistant acid phosphatase, and cathepsin K. This study is the first to show that vitamin C can inhibit osteoporosis by promoting osteoblast formation and blocking osteoclastogenesis through the activation of wingless-type MMTV integration site family/&#946;-catenin/activating transcription factor 4 signaling, which is achieved through the serine/threonine kinase and mitogen-activated protein kinase signaling pathways. Therefore, our results suggest that vitamin C improves bone regeneration