Fibrolamellar hepatocellular carcinoma that was successfully treated with surgical resection: a case report

Fibrolamellar hepatocellular carcinoma (FLHCC) is a rare malignant hepatic cancer with characteristics that differ from those of typical hepatocellular carcinoma (HCC). Unlike conventional HCC, FLHCC is common in young patients without any underlying liver disease and is known to be associated with a unique gene mutation. This cancer type is rare in Asia, with only a few cases being reported in Korea. We report a case of FLHCC in a young woman that successfully underwent surgical resection. The efficacy of alternative treatments, such as transarterial chemoembolization or systemic chemotherapies, has not yet been established. To conclude, early diagnosis and appropriate surgical resection are important for the treatment of FLHCC

The development of hepatocellular carcinoma during long-term treatment for recurrent non-small cell lung cancer: a case report

Multiple primary malignancies (MPMs) are defined as the presence of two or more malignancies in different organs, without a subordinate relationship. Although rarely reported, hepatocellular carcinoma (HCC) occasionally presents with simultaneous or metachronous primary malignancies in other organs. In this report, we describe a patient with lung adenocarcinoma and lymph node and bone metastases, treated with five chemotherapeutic regimens for 24 months. Changing the chemotherapy regimen based on the suspicion of metastasis of a new liver mass did not lead to improvements. This prompted a liver biopsy and a revised diagnosis of HCC. Sixth-line treatment with the concurrent use of cisplatin-paclitaxel for lung cancer and sorafenib for HCC, stabilized the disease. The concurrent treatment was not tolerated and was discontinued owing to adverse events. Considering our findings, treatment with increased efficacy and lower toxicity for MPMs is warranted

Merozoite surface protein 1 paralog is involved in the human erythrocyte invasion of a zoonotic malaria, Plasmodium knowlesi

The zoonotic malaria parasite Plasmodium knowlesi is an important public health concern in Southeast Asia. Invasion of host erythrocytes is essential for parasite growth, and thus, understanding the repertoire of parasite proteins that enable this process is vital for identifying vaccine candidates and how some species are able to cause zoonotic infection. Merozoite surface protein 1 (MSP1) is found in all malaria parasite species and is perhaps the most well-studied as a potential vaccine candidate. While MSP1 is encoded by a single gene in P. falciparum, all other human infective species (P. vivax, P. knowlesi, P. ovale, and P. malariae) additionally encode a divergent paralogue known as MSP1P, and little is known about its role or potential functional redundancy with MSP1. We, therefore, studied the function of P. knowlesi merozoite surface protein 1 paralog (PkMSP1P), using both recombinant protein and CRISPR-Cas9 genome editing. The recombinant 19-kDa C-terminus of PkMSP1P (PkMSP1P-19) was shown to bind specifically to human reticulocytes. However, immunoblotting data suggested that PkMSP1P-19-induced antibodies can recognize PkMSP1-19 and vice versa, confounding our ability to separate the properties of these two proteins. Targeted disruption of the pkmsp1p gene profoundly impacts parasite growth, demonstrating for the first time that PkMSP1P is important in in vitro growth of P. knowlesi and likely plays a distinct role from PkMSP1. Importantly, the MSP1P KO also enabled functional characterization of the PkMSP1P-19 antibodies, revealing clear immune cross-reactivity between the two paralogues, highlighting the vital importance of genetic studies in contextualizing recombinant protein studies

Identification of a reticulocyte-specific binding domain of Plasmodium vivax reticulocyte-binding protein 1 that is homologous to the PfRh4 erythrocyte-binding domain

The Plasmodium vivax reticulocyte-binding protein (RBP) family was identified based on the annotation of adhesive ligands in the P. vivax genome. Reticulocyte-specific interactions with the PvRBPs (PvRBP1 and PvRBP2) were previously reported. Plasmodium falciparum reticulocyte-binding protein homologue 4 (PfRh4, a homologue of PvRBP1) was observed to possess erythrocyte-binding activity via complement receptor 1 on the erythrocyte surface. However, the reticulocyte-binding mechanisms of P. vivax are unclear because of the large molecular mass of PvRBP1 (>326 kDa) and the difficulty associated with in vitro cultivation. In the present study, 34 kDa of PvRBP1a (PlasmoDB ID: PVX_098585) and 32 kDa of PvRBP1b (PVX_098582) were selected from a 30 kDa fragment of PfRh4 for reticulocyte-specific binding activity analysis. Both PvRBP1a and PvRBP1b were found to be localized at the microneme in the mature schizont-stage parasites. Naturally acquired immune responses against PvRBP1a-34 and PvRBP1b-32 were observed lower than PvDBP-RII. The reticulocyte-specific binding activities of PvRBP1a-34 and PvRBP1b-32 were significantly higher than normocyte binding activity and were significantly reduced by chymotrypsin treatment. PvRBP1a and 1b, bind to reticulocytes and that this suggests that these ligands may have an important role in P. vivax merozoite invasion.Publisher PDFPeer reviewe

Identification of a novel merozoite surface antigen of Plasmodium vivax, PvMSA180

Background: Although a number of Plasmodium vivax proteins have been identified, few have been investigated as potential vaccine candidates. This study characterized the Plasmodium vivax merozoite surface antigen 180 (PvMSA180, PVX_094920), a novel P. vivax antigenic protein. Methods: The target gene was amplified as four overlapping domains (D1, D2, D3 and D4) to enable expression of the recombinant protein using cell-free and bacterial expression systems. The recombinant PvMSA180 proteins were used in protein microarrays to evaluate the humoral immune response of 72 vivax-infected patients and 24 vivax-naive individuals. Antibodies produced in mice against the PvMSA180-D1 and -D4 domains were used to assess the subcellular localization of schizont-stage parasites with immunofluorescence assays. A total of 51 pvmsa180 sequences from 12 countries (41 sequences from PlasmoDB and 6 generated in this study) were used to determine the genetic diversity and genealogical relationships with DNAsp and NETWORK software packages, respectively. Results: PvMSA180 consists of 1603 amino acids with a predicted molecular mass of 182 kDa, and has a signal peptide at the amino-terminus. A total of 70.8% of patients (51/72) showed a specific antibody response to at least one of the PvMSA180 domains, and 20.8% (15/72) exhibited a robust antibody response to at least three of the domains. These findings suggest that PvMSA180 is targeted by the humoral immune response during natural infection with P. vivax. Immunofluorescence analysis demonstrated that PvMSA180 is localized on the merozoite surface of schizontstage parasites, and pvmsa180 sequences originating from various geographic regions worldwide showed low genetic diversity. Twenty-two haplotypes were found, and haplotype 6 (Hap_6, 77%) of pvmsa180 was detected in isolates from six countries. Conclusions: A novel P. vivax surface protein, PvMSA180, was characterized in this study. Most of P. vivax-infected patients had specific antibodies against particular antigenic domains, indicating that this protein is immunogenic in naturally exposed populations. Genetic analysis of worldwide isolates showed that pvmsa180 is less polymorphic than other well-known candidates and that some haplotypes are common to several countries. However, additional studies with a larger sample size are necessary to evaluate the antibody responses in geographically separated populations, and to identify the function of PvMSA180 during parasite invasion.Publisher PDFPeer reviewe

Characterization of merozoite-specific thrombospondin-related anonymous protein (MTRAP) in Plasmodium vivax and P. knowlesi parasites

Plasmodium vivax, the most widespread human malaria parasite, and P. knowlesi, an emerging Plasmodium that infects humans, are the phylogenetically closest malarial species that infect humans, which may induce cross-species reactivity across most co-endemic areas in Southeast Asia. The thrombospondin-related anonymous protein (TRAP) family is indispensable for motility and host cell invasion in the growth and development of Plasmodium parasites. The merozoite-specific TRAP (MTRAP), expressed in blood-stage merozoites, is supposed to be essential for human erythrocyte invasion. We aimed to characterize MTRAPs in blood-stage P. vivax and P. knowlesi parasites and ascertain their cross-species immunoreactivity. Recombinant P. vivax and P. knowlesi MTRAPs of full-length ectodomains were expressed in a mammalian expression system. The MTRAP-specific immunoglobulin G, obtained from immune animals, was used in an immunofluorescence assay for subcellular localization and invasion inhibitory activity in blood-stage parasites was determined. The cross-species humoral immune responses were analyzed in the sera of patients with P. vivax or P. knowlesi infections. The MTRAPs of P. vivax (PvMTRAP) and P. knowlesi (PkMTRAP) were localized on the rhoptry body of merozoites in blood-stage parasites. Both anti-PvMTRAP and anti-PkMTRAP antibodies inhibited erythrocyte invasion of blood-stage P. knowlesi parasites. The humoral immune response to PvMTRAP showed high immunogenicity, longevity, and cross-species immunoreactivity with P. knowlesi. MTRAPs are promising candidates for development of vaccines and therapeutics against vivax and knowlesi malaria

Implant surface treatments affect gene expression of Runx2, osteogenic key marker

STATEMENT OF PROBLEM. The aim of this study was to study the effects of various surface treatments to a titanium surface on the expression of Runx2 in vitro. MATERIAL AND METHODS. Human Osteosarcoma TE-85 cells were cultured on machined, sandblasted, or anodic oxidized cpTi discs. At various times of incubation, the cells were collected and then processed for the analysis of mRNA expression of Runx2 using reverse transcription-PCR. RESULTS. The expression pattern of Runx2 mRNA was differed according to the types of surface treatment. When the cells were cultured on the untreated control culture plates, the gene expression of Runx2 was not increased during the experiments. In the case of that the cells were cultured on the machined cpTI discs, the expression level was intermediate at the first day, but increased constitutively to day 5. In cells on sandblasted cpTi discs, the expression level was highest in the first day sample and the level was maintained to 5 days. In cells on anodized cpTi discs, the expression level increased rapidly to 3 days, but decreased slightly in the 5-th day sample. CONCLUSION. Different surface treatments may contribute to the regulation of osteoblast function by influencing the level of gene expression of key osteogenic factors

Clustered LAG-1 binding sites in lag-1/CSL are involved in regulating lag-1 expression during lin-12/Notch-dependent cell-fate specification

The cell-fate specification of the anchor cell (AC) and a ventraluterine precursor cell (VU) in Caenorhabditis elegans isinitiated by a stochastic interaction between LIN-12/Notchreceptor and LAG-2/Delta ligand in two neighboring Z1.pppand Z4.aaa cells. Both cells express lin-12 and lag-2 beforespecification, and a small difference in LIN-12 activity leads tothe exclusive expressions of lin-12 in VU and lag-2 in the AC,through a feedback mechanism of unknown nature. Here weshow that the expression pattern of lag-1/CSL, a transcriptionalrepressor itself that turns into an activator upon binding of theintracellular domain of Notch, overlaps with that of lin-12.Site-directed mutagenesis of LAG-1 binding sites in lag-1maintains its expression in the AC, and eliminates it in the VU.Thus, AC/VU cell-fate specification appears to involve directregulation of lag-1 expression by the LAG-1 protein, activatingits transcription in VU cells, but repressing it in the AC. [BMBReports 2013; 46(4): 219-224

Environmentally safe and renewable solar vapor generation device based on Prussian blue nanoparticles immobilized on cellulose nanofibers

Solar vapor generation is a sustainable solution to overcome the shortage of fresh water. Although several solar vapor generation devices showing significant evaporation rates have been developed over the past years, there are still remaining problems such as fabrication difficulties and potential environmental hazards. In this report, we demonstrate a solar evaporation device composed of agar hydrogel (AHG) and Prussian blue (PB) immobilized on cellulose nanofiber (CNF). The CNF-PB/AHG device shows a high evaporation rate of 2.22 kg m−2 h−1 under one sun illumination arising from the combined effects of the high water-transport performance of CNF/AHG and the good photothermal ability of PB. The device does not exhibit salt fouling or any decline in desalination performance under a long-term day and night simulation due to the salt-rejection ability of AHG. The average fresh water generation in the field test is 5.95 kg m−2 day−1. Furthermore, the used device can be resurrected without decline of the vapor generation performance through a simple re-fabrication process due to the remarkable stability of CNF-PB and reversible sol-gel transition of AHG. In conclusion, the CNF-PB/AHG device is an environmentally safe, low-cost, easily manufacturable, and renewable solar desalination system. © 2021 Elsevier B.V.1

Effects of anodized oxidation or turned implants on bone healing after using conventional drilling or trabecular compaction technique: histomorphometric analysis and RFA

Abstract Objectives: The aim of this study was to compare the bone healing characteristics adjacent to anodic oxidation and turned surfaces after implant installation using the trabecular compaction technique or the conventional drilling technique in the soft bone area. Material and methods: A total of 72 implants (36 anodic oxidation surface and 36 turned surface implants) were inserted into the distal end of the femur head of 12 dogs by two different surgical techniques. There were four experimental groups: (1) DT group; drillingþturned, (2) DO group; drillingþoxidation, (3) CT group; compactionþturned, and (4) CO group; compactionþoxidation. The resonance frequency was measured and six specimens/treatment group were obtained at 0, 3 and 8 weeks, postoperatively. Undecalcified ground sections were prepared for histologic and histomorphometric examinations. Results: At week 0, the trabecular compaction groups showed a higher bone to implant contact ratio (BIC) than the conventional drilling groups, regardless of surface types. The CT group showed a higher implant stability quotient (ISQ) than the DT group. At week 3, the oxidation groups showed a higher BIC than the turned groups regardless of the surgical technique used. The CO group showed higher ISQ than the CT group. At week 8, there was no statistically significant difference in BIC and ISQ between the groups. Conclusions: Surgical technique and implant surface state have an effect on the initial bone response to two-stage implants inserted into trabecular bone regions.This work was supported by a grant from the Korea Health 21 R&D Project, Ministry of Health & Welfare, Republic of Korea (02-PJ3-PG6-EV11-0002). We especially thank Prof. Hyoun-Ee Kim for help with this study