MLN51 and GM-CSF involvement in the proliferation of fibroblast-like synoviocytes in the pathogenesis of rheumatoid arthritis

Rheumatoid arthritis (RA) is an inflammatory autoimmune disease of unclear etiology. This study was conducted to identify critical factors involved in the synovial hyperplasia in RA pathology. We applied cDNA microarray analysis to profile the gene expressions of RA fibroblast-like synoviocytes (FLSs) from patients with RA. We found that the MLN51 (metastatic lymph node 51) gene, identified in breast cancer, is remarkably upregulated in the hyperactive RA FLSs. However, growth-retarded RA FLSs passaged in vitro expressed small quantities of MLN51. MLN51 expression was significantly enhanced in the FLSs when the growth-retarded FLSs were treated with granulocyte – macrophage colony-stimulating factor (GM-CSF) or synovial fluid (SF). Anti-GM-CSF neutralizing antibody blocked the MLN51 expression even though the FLSs were cultured in the presence of SF. In contrast, GM-CSF in SFs existed at a significant level in the patients with RA (n = 6), in comparison with the other inflammatory cytokines, IL-1β and TNF-α. Most RA FLSs at passage 10 or more recovered from their growth retardation when cultured in the presence of SF. The SF-mediated growth recovery was markedly impaired by anti-GM-CSF antibody. Growth-retarded RA FLSs recovered their proliferative capacity after treatment with GM-CSF in a dose-dependent manner. However, MLN51 knock-down by siRNA completely blocked the GM-CSF/SF-mediated proliferation of RA FLSs. Taken together, our results imply that MLN51, induced by GM-CSF, is important in the proliferation of RA FLSs in the pathogenesis of RA

Transdifferentiation-inducing HCCR-1 oncogene

<p>Abstract</p> <p>Background</p> <p>Cell transdifferentiation is characterized by loss of some phenotypes along with acquisition of new phenotypes in differentiated cells. The differentiated state of a given cell is not irreversible. It depends on the up- and downregulation exerted by specific molecules.</p> <p>Results</p> <p>We report here that <it>HCCR-1</it>, previously shown to play an oncogenic role in human cancers, induces epithelial-to-mesenchymal transition (EMT) and mesenchymal-to-epithelial transition (MET) in human and mouse, respectively. The stem cell factor receptor CD117/c-Kit was induced in this transdifferentiated (EMT) sarcoma tissues. This MET occurring in <it>HCCR-1 </it>transfected cells is reminiscent of the transdifferentiation process during nephrogenesis. Indeed, expression of <it>HCCR-1 </it>was observed during the embryonic development of the kidney. This suggests that <it>HCCR-1 </it>might be involved in the transdifferentiation process of cancer stem cell.</p> <p>Conclusions</p> <p>Therefore, we propose that <it>HCCR-1 </it>may be a regulatory factor that stimulates morphogenesis of epithelia or mesenchyme during neoplastic transformation.</p

Regional Variation in States’ Naloxone Accessibility Laws in Association With Opioid Overdose Death Rates-Observational Study (STROBE Compliant)

Though overall death from opioid overdose are increasing in the United States, the death rate in some states and population groups is stabilizing or even decreasing. Several states have enacted a Naloxone Accessibility Laws to increase naloxone availability as an opioid antidote. The extent to which these laws permit layperson distribution and possession varies. The aim of this study is to investigate differences in provisions of Naloxone Accessibility Laws by states mainly in the Northeast and West regions, and the impact of naloxone availability on the rates of drug overdose deaths. This cross-sectional study was based on the National Vital Statistics System multiple cause-of-death mortality files. The average changes in drug overdose death rates between 2013 and 2017 in relevant states of the Northeast and West regions were compared according to availability of naloxone to laypersons. Seven states in the Northeast region and 10 states in the Western region allowed layperson distribution of naloxone. Layperson possession of naloxone was allowed in 3 states each in the Northeast and the Western regions. The average drug overdose death rates increased in many states in the both regions regardless of legalization of layperson naloxone distribution. The average death rates of 3 states that legalized layperson possession in the West region decreased (-0.33 per 100,000 person); however, in states in the West region that did not allow layperson possession and states in the Northeast region regardless of layperson possession increased between 2013 and 2017. The provision to legalize layperson possession of naloxone was associated with decreased average opioid overdose death rates in 3 states of the West region

Combined analysis of AFP and HCCR-1 as an useful serological marker for small hepatocellular carcinoma: a prospective cohort study

Abstract. Hepatocellular carcinoma (HCC) is one of the most frequent malignant tumors in the world. The only serological marker widely used for the diagnosis of HCC is alpha-fetoprotein (AFP). Despite that AFP is widely used for the diagnosis of HCC, it has a limit as a serological marker due to its low sensitivity and specificity. The human cervical cancer proto-oncogene 1 (HCCR-1) was previously reported as a new biomarker for HCC. To further evaluate the HCCR-1 as a biomarker for HCC, we conducted the prospective cohort study. We evaluated the significance of simultaneous measurement of 2 tumor markers in the diagnosis of HCC in China, Japan and Korea. Two markers for HCC, AFP and HCCR-1, were measured in the sera obtained from 1,338 patients at the time of initial diagnosis of HCC. Of the 1338 HCC patients, 616 (46%) and 686 (51.3%) were sero-positive for AFP and HCCR-1, respectively. The positive rate for HCC was increased up to 74.1% in combined use of AFP and HCCR-1. Many cases (54%) for AFP-negative HCC were positive for HCCR-1 and vice versa. More importantly, the diagnostic rate for small HCC (&lt; 2 cm) was significantly improved in the combined analysis of AFP and HCCR-1 to 56.9% although it was only 40.1% and 23.4% in the single analysis of HCCR-1 and AFP, respectively. Our result suggests that the HCCR-1 could be an useful biomarker for HCC while the diagnostic rate could be significantly improved in the combined use of HCCR-1 and AFP

History of sunscreen: An updated view.

BACKGROUND With the global sunscreen market expected to reach $24.4 billion worldwide by 2029, this demonstrates the increasing awareness of the damaging effects of sunlight. Sunscreen has been gradually evolving, and new photoprotective ingredients are continuing to be produced in response to growing scientific evidence on the effect of solar radiation on the skin. AIMS This literature review aims to provide an updated view of the history of sunscreens. METHODS A literature search was conducted with the keywords "Sunscreen, history, regulation, ultraviolet A, ultraviolet B, visible light" from PubMed, Medline, and online search engines. RESULTS Humankind has always found ways to provide photoprotection since 4000BC. Only in the last century, evidence-based sunscreens have existed. The first ultraviolet B filters were produced in 1928, its evidence of efficacy and safety discovered in 1956 and development of sun protection factor in 1974. Similarly, sunscreen containing ultraviolet A filters was released in 1980 and the ultraviolet A star rating system developed in 1992. Regulatory bodies for sunscreen were introduced in the 1970s and have sought to review the safety and efficacy of ingredients. With the rising number of researches on the effects of visible light on hyperpigmentation over the past decade, the need for photoprotection beyond ultraviolet has been increasing. CONCLUSION To provide consumers with evidence-based sunscreen, challenges remain in acquiring further evidence, regulation, and rating systems

Skin Care for Acute Care Patients

Objectives Understand: Wound etiology Staging of pressure injury Treatment/formulary Wound documentation Resources available to clinician

A case report on the use of topical cysteamine 5% cream in the management of refractory postinflammatory hyperpigmentation (PIH) resistant to triple combination cream (hydroquinone, topical corticosteroids, and retinoids).

BACKGROUND Postinflammatory hyperpigmentation (PIH) occurs as a result of different inflammatory dermatoses and exogenous factors in individuals with darker skin types. With current skin lightening treatments, there are concerns about irritation leading to worsening of their underlying inflammatory skin condition or worsening of PIH. CASE A 20-year-old woman with Fitzpatrick skin type (FST) V presented with facial hyperpigmented patches since childhood following an intermittent erythematous, pruritic facial rash. Skin biopsy confirmed PIH secondary to possible burnt-out morphea. Treatment with topical adapalene 0.1% gel and triple combination cream (containing hydroquinone, topical corticosteroids, and retinoids) proved unsuccessful. Treatment with cysteamine 5% cream over 4 months resulted in significant improvement with a reduction in the melanin index. DISCUSSION The current recommendation for first-line treatment in PIH is hydroquinone or triple combination cream containing hydroquinone, which can be associated with significant short- and long-term side effects. Cysteamine 5% cream is one of the latest cosmetic skin lightening products. It is hypothesized that cysteamine reduces melanin production by inhibiting key melanogenic enzymes required in melanogenesis. Its efficacy and tolerability have been demonstrated in two randomized controlled trials against placebo in patients with melasma. This report demonstrates a successful use of cysteamine 5% cream in a patient with chronic severe PIH

Vitamin D Intake and Serum 25-Hydroxyvitamin D Levels in Korean Adults: Analysis of the 2009 Korea National Health and Nutrition Examination Survey (KNHANES IV-3) Using a Newly Established Vitamin D Database

Vitamin D is important for maintaining bone health and may prevent various diseases (i.e., cardiovascular disease and cancer). The aim of this study was to estimate vitamin D intakes of Korean adults using the Korea National Health and Nutrition Examination Survey (KNHANES, 2009) data and a newly established vitamin D database. KNHANES (2009) participants (n = 4541; 2021 men; 2520 women) aged ≥20 years were included. Dietary vitamin D intake, serum 25-hydroxyvitamin D (25(OH)D), and the relationship between vitamin D intake and serum 25(OH)D were evaluated. In men and women, vitamin D intakes were 4.00 ± 0.17 µg/day and 2.6 ± 0.1 µg/day respectively, and serum 25(OH)D concentrations were 19.78 ± 0.33 ng/mL and 17.10 ± 0.26 ng/mL respectively. Serum 25(OH)D concentrations of men aged &lt;50 years and women aged &gt;20 years were under 20 ng/mL. After adjusting for confounding factors, the positive relationship between vitamin D intake and serum 25(OH)D was observed in total subjects (p &lt; 0.05), excluding participants ≥50 years old. The main food sources for vitamin D among Korean adults were fish/shellfish (71.34%) and egg (14.89%). Korean adults should increase their serum 25(OH)D concentrations by increasing vitamin D intake

3D Bioprinting-Based Vascularized Tissue Models Mimicking Tissue-Specific Architecture and Pathophysiology for in vitro Studies

A wide variety of experimental models including 2D cell cultures, model organisms, and 3D in vitro models have been developed to understand pathophysiological phenomena and assess the safety and efficacy of potential therapeutics. In this sense, 3D in vitro models are an intermediate between 2D cell cultures and animal models, as they adequately reproduce 3D microenvironments and human physiology while also being controllable and reproducible. Particularly, recent advances in 3D in vitro biomimicry models, which can produce complex cell structures, shapes, and arrangements, can more similarly reflect in vivo conditions than 2D cell culture. Based on this, 3D bioprinting technology, which enables to place the desired materials in the desired locations, has been introduced to fabricate tissue models with high structural similarity to the native tissues. Therefore, this review discusses the recent developments in this field and the key features of various types of 3D-bioprinted tissues, particularly those associated with blood vessels or highly vascularized organs, such as the heart, liver, and kidney. Moreover, this review also summarizes the current state of the three categories: (1) chemical substance treatment, (2) 3D bioprinting of lesions, and (3) recapitulation of tumor microenvironments (TME) of 3D bioprinting-based disease models according to their disease modeling approach. Finally, we propose the future directions of 3D bioprinting approaches for the creation of more advanced in vitro biomimetic 3D tissues, as well as the translation of 3D bioprinted tissue models to clinical applications.11Nsciescopu