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Abstract Sun-protective strategies focusing on skin cancer awareness are needed in immunosuppressed patients at risk of skin cancers. The study aims to determine the effect of an integrated skin cancer education program on skin cancer awareness and sun-protective behaviours in renal transplant recipients (RTRs) and patients with glomerular disease (GD) treated with long-term immunosuppressants. A pilot prospective cohort study in Central Queensland, Australia was undertaken among adult RTRs and patients with GD, who completed survey questionaries on skin cancer and sun-health knowledge (SCSK), sun-protection practices and skin examination pre- and post-education. Fifty patients (25 RTRs, 25 patients with GD) participated in the study. All of them completed questionnaires at pre-, 3-month post-education and 92%(n = 46) at 6-month post-education. There was a significant increase in SCSK scores from baseline at 3-months (p

The increased cancer incidence in patients with glomerular disease can be secondary to an intrinsic immune dysfunction associated with the disease or/and extrinsic factors, especially immunosuppressants. The treatment for paraneoplastic glomerulopathy is different from primary glomerular disease. Immunosuppressive therapy often used for primary glomerulopathy may aggravate concomitant cancers in patients with paraneoplastic glomerulopathy. In membranous nephropathy (MN), measurement of serum circulating autoantibodies against podocyte transmembrane glycoprotein M-type phospholipase A2 receptor (PLA2R) and thrombospondin type 1 domain-containing 7A (THSD7A), immunohistochemical staining of kidney tissue for glomerular PLA2R, THSD7A, neural epidermal growth factor-like 1 protein (NELL-1) and specific types of immunoglobulin G (IgG) may be useful adjuncts when screening for underlying malignancies. This review addresses overall cancer risks in individuals with glomerular diseases and employment of biomarkers available for MN. We propose a scheme of screening of cancers frequently reported in the setting of glomerular disease.

Fenofibrate (FE) has been shown to markedly reduce the progression of diabetic retinopathy and age-related macular degeneration in clinical trials and animal models. Owing to the limited aqueous solubility of FE, it may hamper ocular bioavailability and result in low efficiency to treat such diseases. To enhance the solubility of FE, water-soluble FE/cyclodextrin (CD) complex formation was determined by a phase-solubility technique. Randomly methylated-β-CD (RMβCD) exhibited the best solubility and the highest complexation efficiency (CE) for FE. Additionally, water-soluble polymers (i.e., hydroxypropyl methyl cellulose and polyvinyl alcohol [PVA]) enhanced the solubility of FE/RMβCD complexes. Solid- and solution-state characterizations were performed to elucidate and confirm the formation of inclusion FE/RMβCD complex. FE-loaded Eudragit® nanoparticle (EuNP) dispersions and suspensions were developed. The physicochemical properties (i.e., pH, osmolality, viscosity, particle size, size distribution, and zeta potential) were within acceptable ranges. Moreover, in vitro mucoadhesion, in vitro release, and in vitro permeation studies revealed that the FE-loaded EuNP eye drop suspensions had excellent mucoadhesive properties and sustained FE release. The hemolytic activity, hen’s egg test on chorioallantoic membrane assay, and in vitro cytotoxicity test showed that the FE formulations had low hemolytic activity, were cytocompatible, and were moderately irritable to the eyes. In conclusion, PVA-stabilized FE/RMβCD-loaded EuNP eye drop suspensions were successfully developed, warranting further in vivo testing.

Rapid urbanization has beset sustainable consumption. Although many countries are increasingly taking pro-environmental stances, most countries continue to have a low recycling rate and a high littering rate. This study examines the effect of temporal distance as a part of Construal-Level Theory and descriptive norms on pro- and contra-environmental behaviors (i.e., recycling and littering) cross-culturally. Participants were recruited from the United States and South Korea, and randomly assigned to one of five versions of the survey. Findings indicated stronger intention to recycle for the distant future (only 3-year) and no significant difference for littering. Americans showed higher likelihood to recycle than Koreans while Koreans showed higher likelihood to litter when temporal distance was disregarded. Situational descriptive norms showed significant differences cross-culturally, but the interaction of culture and time distance was not visible. Theoretical implications for Construal-Level Theory research and practical implications for environmental policymakers in encouraging pro-environmental behaviors are discussed.

Acinetobacter baumannii is a nosocomial pathogen that frequently causes healthcare-acquired infections. The global spread of multidrug-resistant (MDR) strains with its ability to survive in the environment for extended periods imposes a pressing public health threat. Two MDR A. baumannii outbreaks occurred in 2012 and 2014 in a companion animal intensive care unit (caICU) in the Netherlands. Whole-genome sequencing (WGS) was performed on dog clinical isolates (n = 6), environmental isolates (n = 5), and human reference strains (n = 3) to investigate if the isolates of the two outbreaks were related. All clinical isolates shared identical resistance phenotypes displaying multidrug resistance. Multi-locus Sequence Typing (MLST) revealed that all clinical isolates belonged to sequence type ST2. The core genome MLST (cgMLST) results confirmed that the isolates of the two outbreaks were not related. Comparative genome analysis showed that the outbreak isolates contained different gene contents, including mobile genetic elements associated with antimicrobial resistance genes (ARGs). The time-measured phylogenetic reconstruction revealed that the outbreak isolates diverged approximately 30 years before 2014. Our study shows the importance of WGS analyses combined with molecular clock investigations to reduce transmission of MDR A. baumannii infections in companion animal clinics.

We believe that researching the cuisine consumed by the royal family, in particular the king, during the 500-year long Chosun Dynasty is an interesting and meaningful endeavor. This task is an important part of unraveling the cultural significance of Korean cuisine in the 21st century, a new age of gastronomy. Until now, research has largely focused on recreating Chosun royal cuisine based on oral statements from staff in the last royal kitchen or the Uikwe (儀軌), the Royal Protocols which recorded food consumed at banquets. However, little research has been conducted on ordinary royal cuisine consumed by the king, mainly because of a lack of materials to study. This article aims to shed light on this topic and recreate what every day royal cuisine looked like in the late stages of the Chosun Dynasty by examining joseoksangsikbalgi (朝夕上食撥記, memos of morning and evening ancestral rites table) and judaryebalgi (晝茶禮撥記, memos of daytime tea ceremonies). The memos are similar to the chanpumdanja (饌品單子, literally meaning “a list of dishes served on the table”) that recorded national banquets and therefore do not contain records of ordinary royal cuisine. However, the memos of morning and evening ancestral rites table still remain. These documents describe food offered to the deceased, which was the same as the meals they regularly ate while alive. Accordingly, we attempted to reproduce the traditional table setting for ordinary royal cuisine served to King Kojong (高宗) by analyzing these memos. King Kojong (1852–1919) was the 26th king of the Chosun Dynasty, and a detailed description of the sangsik (上食, ancestral rites table) prepared following his death in January 1919 is present in the morning and evening sangsik memos and daytime tea ceremony memos from October 11, 1919. After analyzing the memos from after King Kojong's death in 1919, we were able to determine that the cuisine consisted of rice as bap (a main staple rice), kuk (a kind of soup), tang (stew), banchan (side dishes) such as meat, jeok (skewers), jeon (Korean pancakes), greens and salted dry fish, kimchi, seasonings such as soy sauce, kochujang (red pepper paste) and mustard as well as fruits and fruit salad for dessert. We determined that in addition to bap (rice), kuk (soup), tang (stew), kimchi and sauces, there were 7–9 banchan (side dishes) that served to create a balanced meal. On examination of the esthetic elements of Chosun royal cuisine, we found that the cuisine followed Confucian customs and formalities, and the kobaeumsik (고배음식, religious food serviced by layer upon layer) that symbolizes the power of the king. In addition to this, royal cuisine also embodied the philosophy of yaksikdongwon (藥食同源), an ideology which focuses on the health function of food. It was also nutritionally balanced and achieved synergy between yin (陰) and yang (陽). We believe that studying the cuisine of the Chosun royal family will ultimately play a role in spreading awareness about Korean royal cuisine around the world and creating materials that can be referred to for further research on royal cuisine and culture. However, we cannot be certain that the records present in the sangsik memos are truly representative of what the king ate on a daily basis, and more detailed analysis is required on this point.

Cisplatin is a platinum-based compound that is widely used for treating inoperable oral squamous cell carcinoma (OSCC) in Japan; however, resistance to cisplatin presents a challenge and innovative approaches are required. We aimed to investigate the therapeutic potential of targeting the chemokine receptor CXCR4, which is involved in angiogenesis and tumor progression, using the CXCR4 inhibitor AMD3100, in combination with cisplatin. AMD3100 induced necrosis and bleeding in OSCC xenografts by inhibiting angiogenesis. We investigated the combined ability of AMD3100 plus cisplatin to enhance the antitumor effect in cisplatin-resistant OSCC. An MTS assay identified HSC-2 cells as cisplatin-resistant cells in vitro. Mice treated with the cisplatin-AMD combination exhibited the most significant reduction in tumor volume, accompanied by extensive hemorrhage and necrosis. Histological examination indicated thin and short tumor vessels in the AMD and cisplatin-AMD groups. These results indicated that cisplatin and AMD3100 had synergistic antitumor effects, highlighting their potential for vascular therapy of refractory OSCC. Antitumor vascular therapy using cisplatin combined with a CXCR4 inhibitor provides a novel strategy for addressing cisplatin-resistant OSCC.

Because cancer cells have a genetically unstable nature, they give rise to genetically different variant subclones inside a single tumor. Understanding cancer heterogeneity and subclone characteristics is crucial for developing more efficacious therapies. Oral squamous cell carcinoma (OSCC) is characterized by high heterogeneity and plasticity. On the other hand, CX3C motif ligand 1 (CX3CL1) is a double-faced chemokine with anti- and pro-tumor functions. Our study reported that CX3CL1 functioned differently in tumors with different cancer phenotypes, both in vivo and in vitro. Mouse OSCC 1 (MOC1) and MOC2 cells responded similarly to CX3CL1 in vitro. However, in vivo, CX3CL1 increased keratinization in indolent MOC1 cancer, while CX3CL1 promoted cervical lymphatic metastasis in aggressive MOC2 cancer. These outcomes were due to double-faced CX3CL1 effects on different immune microenvironments indolent and aggressive cancer created. Furthermore, we established that CX3CL1 promoted cancer metastasis via the lymphatic pathway by stimulating lymphangiogenesis and transendothelial migration of lymph-circulating tumor cells. CX3CL1 enrichment in lymphatic metastasis tissues was observed in aggressive murine and human cell lines. OSCC patient samples with CX3CL1 enrichment exhibited a strong correlation with lower overall survival rates and higher recurrence and distant metastasis rates. In conclusion, CX3CL1 is a pivotal factor that stimulates the metastasis of aggressive cancer subclones within the heterogeneous tumors to metastasize, and our study demonstrates the prognostic value of CX3CL1 enrichment in long-term monitoring in OSCC.

Mesenchymal stem cell (MSC) therapy is a promising approach to curing bone diseases and disorders. In treating genetic bone disorders, MSC therapy is local or systemic transplantation of isolated and in vitro proliferated MSC rather than bone marrow transplantation. Recent evidence showed that bone marrow MSC engraftment to bone regeneration has been controversial in animal and human studies. Here, our modified bone marrow transplantation (BMT) method solved this problem. Like routine BMT, our modified method involves three steps: (i) isolation of bone marrow cells from the donor, (ii) whole-body lethal irradiation to the recipient, and (iii) injection of isolated bone marrow cells into irradiated recipient mice via the tail vein. The significant modification is imported at the bone marrow isolation step. While the bone marrow cells are flushed out from the bone marrow with the medium in routine BMT, we applied the enzymes' (collagenase type 4 and dispase) integrated medium to wash out the bone marrow cells. Then, cells were incubated in enzyme integrated solution at 37°C for 10 minutes. This modification designated BMT as collagenase-integrated BMT (c-BMT). Notably, successful engraftment of bone marrow MSC to the new bone formation, such as osteoblasts and chondrocytes, occurs in c-BMT mice, whereas routine BMT mice do not recruit bone marrow MSC. Indeed, flow cytometry data showed that c-BMT includes a higher proportion of LepR + , CD51 + , or RUNX2 + non-hematopoietic cells than BMT. These findings suggested that c-BMT is a time-efficient and more reliable technique that ensures the disaggregation and collection of bone marrow stem cells and engraftment of bone marrow MSC to the recipient. Hence, we proposed that c-BMT might be a promising approach to curing genetic bone disorders. © 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research., Competing Interests: The authors declare no conflicts of interest., (© 2023 The Authors. JBMR Plus published by Wiley Periodicals LLC on behalf of American Society for Bone and Mineral Research.)

Tumor angiogenesis is one of the hallmarks of solid tumor development. The progressive tumor cells produce the angiogenic factors and promote tumor angiogenesis. However, how the tumor stromal cells influence tumor vascularization is still unclear. In the present study, we evaluated the effects of oral squamous cell carcinoma (OSCC) stromal cells on tumor vascularization. The tumor stromal cells were isolated from two OSCC patients with different subtypes: low invasive verrucous squamous carcinoma (VSCC) and highly invasive squamous cell carcinoma (SCC) and co-xenografted with the human OSCC cell line (HSC-2) on nude mice. In comparison, the CD34+ vessels in HSC-2+VSCC were larger than in HSC-2+SCC. Interestingly, the vessels in the HSC-2+VSCC expressed vascular endothelial cadherin (VE-cadherin), indicating well-formed vascularization. Our microarray data revealed that the expression of extracellular superoxide dismutase, SOD3 mRNA is higher in VSCC stromal cells than in SCC stromal cells. Moreover, we observed that SOD3 colocalized with VE-cadherin on endothelial cells of low invasive stroma xenograft. These data suggested that SOD3 expression in stromal cells may potentially regulate tumor vascularization in OSCC. Thus, our study suggests the potential interest in SOD3-related vascular integrity for a better OSCC therapeutic strategy.

Background: The recent emergence and spread of antimicrobial-resistant Neisseria gonorrhoeae has compromised treatment and control of gonorrhea. We determined recent trends in antimicrobial susceptibility of the isolates, analyzed recent use of antigonococcal agents, and investigated the relationship between fluoroquinolone nonsusceptibility and amino acid substitutions within the fluoroquinolone resistance-determining regions in Korea., Methods: The antimicrobial susceptibilities of 977 isolates of N. gonorrhoeae collected from 2000 to 2006 in Korea were determined with penicillin, ceftriaxone, spectinomycin, tetracycline, and ciprofloxacin disks. Some of the randomly selected isolates were tested by the Clinical and Laboratory Standards Institute agar dilution method, to determine subtle changes in susceptibility to the above antibiotics and cefixime. β-lactamase was detected using a cefinase disk., Results: All of the isolates exhibited plasmid- or chromosomally mediated resistance to penicillin; however, the proportions of penicillinase-producing N. gonorrhoeae decreased rapidly from 64% in 2000 to 21% in 2006. All isolates were susceptible to third-generation cephalosporins, except for 1 isolate that was not susceptible to cefixime. The proportion of ciprofloxacin-resistant isolates increased from 26% in 2000 to 83% in 2006. Of 7 substitution types, 5 (Ser-91-Phe in Gyrase A (GyrA), Ser-87-Arg in ParC subunit of topoisomerase IV (ParC); Ser-91-Phe and Asp-95-Ala in GyrA, and Ser-87-Asn in ParC; Ser-91-Phe and Asp-95-Gly in GyrA, and Asp-86-Asn in ParC; Ser-91-Tyr in GyrA; Ser-91-Phe in GyrA, and Asp-86-Asn in ParC) were new ones not identified in our 2004 study. All isolates were susceptible to spectinomycin. About half of the patients in our current study (52.6%-58.1%, depending on the year) received spectinomycin treatment. Majorities were resistant to tetracycline, and the rate of highly tetracycline-resistant N. gonorrhoeae increased from 3% in 2000 to 9% in 2006., Conclusions: The incidence of penicillinase-producing N. gonorrhoeae declined significantly, but none of the isolates were susceptible to penicillin G. All isolates were susceptible to spectinomycin, in contrast majority were resistant to tetracycline. Inappropriate use of fluoroquinolone was frequent. The minimum inhibitory concentrations of ceftriaxone were within the susceptible range for all isolates, but those of cefixime were slightly higher, and it was 0.5 μg/mL (nonsusceptible) for 1 isolate.

We present a case of a patient with metastatic nasopharyngeal carcinoma who failed two lines of palliative combination chemotherapy and was treated with allogeneic nonmyeloablative stem cell transplantation (NST). This patient achieved a durable tumor response, dramatic relief of his symptoms, and elimination of tumor in his bone marrow-an effect likely achieved via a graft-versus-tumor response. Although NST has been explored previously in solid tumors, such as renal cell carcinoma and breast cancer, it has not been widely explored in nasopharyngeal carcinoma. We also present data from a flow cytometric immune analysis and cytokine enzyme-linked immunosorbent assay analysis in the pre- and post-NST period.

PURPOSE: We evaluated the clinical benefit of an allogeneic melanoma cell lysate (MCL)-pulsed autologous dendritic cell (DC) vaccine in advanced colorectal cancer patients expressing at least one of six MAGE-A antigens overexpressed by the cell line source of the lysate. EXPERIMENTAL DESIGN: DCs were cultured from peripheral blood mononuclear cells (PBMC), pulsed with the allogeneic MCL, and matured using cytokines that achieved high CD83- and CCR7-expressing DCs. Each patient received up to 10 intradermal vaccinations (3-5 x 10(6) cells per dose) at biweekly intervals. RESULTS: Twenty patients received a total of 161 vaccinations. Treatment was well tolerated and quality of life measurements did not vary much across time. One patient experienced partial response [5%; 95% confidence interval (CI), 1-24%] and seven achieved stable disease (35%; 95% CI, 18-57%), one of whom also achieved late tumor regression, yielding a clinical benefit response rate of 40% (95% CI, 22-61%). Although overall median progression-free survival was 2.4 months (95% CI, 1.9-4.1 months), five patients (25%) experienced prolonged progression-free survival (>6 months), two of whom (10%) remain progression-free for >27 and >37 months, respectively. This result is particularly meaningful as all patients had progressive disease before treatment. Overall, DC vaccination was associated with a serial decline in regulatory T cells. Using an antibody array, we characterized plasma protein profiles in responding patients that may correlate with vaccine activity and report a prevaccination protein signature distinguishing responders from nonresponders. CONCLUSION: This phase II vaccine study using mature, MCL-pulsed DCs has shown promising results and warrants further evaluation in a prospective randomized setting. (Clin Cancer Res 2009;15(24):7726-36).

G-CSF can induce functional immune tolerance in man. In this study, purified T cells from G-CSF-mobilized peripheral blood stem cell (PBSC) donors were analysed by gene expression profiling and immunophenotyping. Results suggested a predominantly immune tolerant profile with upregulation of genes related to Th2 and Treg cells, downregulation of genes associated with Th1 cells, cytotoxicity, antigen presentation and graft-versus-host disease (GVHD) and overexpression of negative regulators of Th17 differentiation. Immunophenotyping revealed that during G-CSF exposure donors had reduced levels of T cells with a Th17 phenotype (CD4+IL-17A+CCR6+IL-23R+), more than three times lower compared to normal controls. G-CSF also led to increased levels of CD4+CD25highCD45RO+ Treg cells. Furthermore, mRNA levels of RORgammat, a Th17-specific transcription factor, decreased in T cells isolated from G-CSF-mobilized PBSC harvests. Th17 cells have been implicated in autoimmune diseases and GVHD pathophysiology. Our study is the first to report the effect of G-CSF on the Th17 subpopulation.