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1.
ACS Omega ; 9(19): 21467-21483, 2024 May 14.
Article in English | MEDLINE | ID: mdl-38764654

ABSTRACT

Osteoarthritis (OA) is a chronic musculoskeletal disorder characterized by cartilage degeneration and synovial inflammation. Paracrine interactions between chondrocytes and macrophages play an essential role in the onset and progression of OA. In this study, in replicating the inflammatory response during OA pathogenesis, chondrocytes were treated with interleukin-1ß (IL-1ß), and macrophages were treated with lipopolysaccharide and interferon-γ. In addition, a coculture system was developed to simulate the biological situation in the joint. In this study, we examined the impact of hyaluronic acid (HA) viscosupplement, particularly Hyruan Plus, on chondrocytes and macrophages. Notably, this viscosupplement has demonstrated promising outcomes in reducing inflammation; however, the underlying mechanism of action remains elusive. The viscosupplement attenuated inflammation, showing an inhibitory effect on nitric oxide production, downregulating proinflammatory cytokines such as matrix metalloproteinases (MMP13 and MMP3), and upregulating the expression levels of type II collagen and aggrecan in chondrocytes. HA also reduced the expression level of inflammatory cytokines such as IL-1ß, TNF-α, and IL-6 in macrophages, and HA exerted an overall protective effect by partially suppressing the MAPK pathway in chondrocytes and p65/NF-κB signaling in macrophages. Therefore, HA shows potential as a viscosupplement for treating arthritic joints.

2.
Int J Stem Cells ; 2024 Jan 22.
Article in English | MEDLINE | ID: mdl-38246659

ABSTRACT

Osteoarthritis (OA) is a joint disorder caused by wear and tear of the cartilage that cushions the joints. It is a progressive condition that can cause significant pain and disability. Currently, there is no cure for OA, though there are treatments available to manage symptoms and slow the progression of the disease. A chondral defect is a common and devastating lesion that is challenging to treat due to its avascular and aneural nature. However, there are conventional therapies available, ranging from microfracture to cell-based therapy. Anyhow, its efficiency in cartilage defects is limited due to unclear cell viability. Exosomes have emerged as a potent therapeutic tool for chondral defects because they are a complicated complex containing cargo of proteins, DNA, and RNA as well as the ability to target cells due to their phospholipidic composition and the altering exosomal contents that boost regeneration potential. Exosomes are used in a variety of applications, including tissue healing and anti-inflammatory therapy. As in recent years, biomaterials-based bio fabrication has gained popularity among the many printable polymer-based hydrogels, tissue-specific decellularized extracellular matrix might boost the effects rather than an extracellular matrix imitating environment, a short note has been discussed. Exosomes are believed to be the greatest alternative option for current cell-based therapy, and future progress in exosome-based therapy could have a greater influence in the field of orthopaedics. The review focuses extensively on the insights of exosome use and scientific breakthroughs centered OA.

4.
Biomater Sci ; 11(19): 6587-6599, 2023 Sep 26.
Article in English | MEDLINE | ID: mdl-37605799

ABSTRACT

Mesenchymal stem cells (MSCs) rely on chemokines and chemokine receptors to execute their biological and physiological functions. Stromal cell-derived factor-1 (SDF-1) is upregulated in injury sites, where it acts as a chemotactic agent, attracting CXCR4-expressing MSCs, which play a pivotal role in the healing and regeneration of tissue throughout the body. Furthermore, SDF-1 expression has been observed in regions experiencing inflammation-induced bone destruction and fracture sites. In this study, we identified a novel peptide called bone-forming peptide-5 (BFP-5), derived from SDF-1δ, which can promote the osteogenesis of MSCs as well as bone formation and healing. Multipotent bone marrow stromal cells treated with BFP-5 showed enhanced alizarin red S staining and higher alkaline phosphatase (ALP) activity. Moreover, ALP and osterix proteins were more abundantly expressed when cells were treated with BFP-5 than SDF-1α. Histology and microcomputed tomography data at 12 weeks demonstrated that both rabbit and goat models transplanted with polycaprolactone (PCL) scaffolds coated with BFP-5 showed significantly greater bone formation than animals transplanted with PCL scaffolds alone. These findings suggest that BFP-5 could be useful in the development of related therapies for conditions associated with bones.


Subject(s)
Mesenchymal Stem Cells , Osteogenesis , Animals , Rabbits , X-Ray Microtomography , Cell Differentiation , Stromal Cells/metabolism , Bone Morphogenetic Proteins/metabolism , Chemokine CXCL12/pharmacology , Chemokine CXCL12/metabolism , Bone Marrow Cells
5.
Int J Mol Sci ; 24(15)2023 Jul 31.
Article in English | MEDLINE | ID: mdl-37569659

ABSTRACT

Osteoarthritis (OA) is characterized by degeneration of the joint cartilage, inflammation, and a change in the chondrocyte phenotype. Inflammation also promotes cell hypertrophy in human articular chondrocytes (HC-a) by activating the NF-κB pathway. Chondrocyte hypertrophy and inflammation promote extracellular matrix degradation (ECM). Chondrocytes depend on Smad signaling to control and regulate cell hypertrophy as well as to maintain the ECM. The involvement of these two pathways is crucial for preserving the homeostasis of articular cartilage. In recent years, Polynucleotides Highly Purified Technology (PN-HPT) has emerged as a promising area of research for the treatment of OA. PN-HPT involves the use of polynucleotide-based agents with controlled natural origins and high purification levels. In this study, we focused on evaluating the efficacy of a specific polynucleotide sodium agent, known as CONJURAN, which is derived from fish sperm. Polynucleotides (PN), which are physiologically present in the matrix and function as water-soluble nucleic acids with a gel-like property, have been used to treat patients with OA. However, the specific mechanisms underlying the effect remain unclear. Therefore, we investigated the effect of PN in an OA cell model in which HC-a cells were stimulated with interleukin-1ß (IL-1ß) with or without PN treatment. The CCK-8 assay was used to assess the cytotoxic effects of PN. Furthermore, the enzyme-linked immunosorbent assay was utilized to detect MMP13 levels, and the nitric oxide assay was utilized to determine the effect of PN on inflammation. The anti-inflammatory effects of PN and related mechanisms were investigated using quantitative PCR, Western blot analysis, and immunofluorescence to examine and analyze relative markers. PN inhibited IL-1ß induced destruction of genes and proteins by downregulating the expression of MMP3, MMP13, iNOS, and COX-2 while increasing the expression of aggrecan (ACAN) and collagen II (COL2A1). This study demonstrates, for the first time, that PN exerted anti-inflammatory effects by partially inhibiting the NF-κB pathway and increasing the Smad2/3 pathway. Based on our findings, PN can potentially serve as a treatment for OA.


Subject(s)
NF-kappa B , Osteoarthritis , Animals , Humans , Male , NF-kappa B/metabolism , Matrix Metalloproteinase 13/genetics , Matrix Metalloproteinase 13/metabolism , Polynucleotides/pharmacology , Polynucleotides/metabolism , Polynucleotides/therapeutic use , Cells, Cultured , Semen/metabolism , Inflammation/drug therapy , Inflammation/metabolism , Osteoarthritis/metabolism , Chondrocytes/metabolism , Anti-Inflammatory Agents/pharmacology , Hypertrophy/metabolism , Interleukin-1beta/metabolism
6.
Saudi J Gastroenterol ; 29(1): 53-58, 2023.
Article in English | MEDLINE | ID: mdl-36571385

ABSTRACT

Background: Methylene blue (MB) is used endoscopically to demarcate tumors and as a photosensitizer in photodynamic therapy (PDT). However, there are few in vivo studies about its toxicity in healthy stomach tissue. We performed sequential in vitro and in vivo analyses of MB-induced phototoxicity. Methods: We performed in vitro experiments using the AGS human gastric cancer cell line treated with light-emitting diode (LED) irradiation (3.6 J/cm2) and MB. Cytotoxicity was evaluated using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. In vivo toxicity was evaluated in the stomach of beagles using the same dose of fiber-optic LED via gastroscopy, after spraying 0.1% and 0.5% MB solutions. Stomach tissue was also evaluated using the TUNEL assay. Results: In vitro, increased concentrations of MB led to higher TUNEL scores. However, cell viability was significantly lower after MB plus LED irradiation than after treatment with MB alone (P < 0.001). In vivo, the TUNEL score was highest immediately after treatment with 0.1% or 0.5% MB plus light irradiation, and the score was significantly higher in the LED illumination plus MB group than in the control group (P < 0.05). The elevated TUNEL score was maintained for 3 days in the MB plus light irradiation group but returned to normal levels on day 10. Conclusions: : Endoscopic light application with MB 0.5% concentration to the stomach may be regarded as a safe procedure despite some DNA injuries in the early period.


Subject(s)
Methylene Blue , Photochemotherapy , Dogs , Animals , Humans , Methylene Blue/pharmacology , Methylene Blue/therapeutic use , Photochemotherapy/methods , Photosensitizing Agents/toxicity , Photosensitizing Agents/therapeutic use , Cell Line , Gastric Mucosa
7.
Int J Mol Sci ; 23(21)2022 Oct 27.
Article in English | MEDLINE | ID: mdl-36361805

ABSTRACT

Osteoarthritis (OA) is a low-grade inflammatory disorder of the joints that causes deterioration of the cartilage, bone remodeling, formation of osteophytes, meniscal damage, and synovial inflammation (synovitis). The synovium is the primary site of inflammation in OA and is frequently characterized by hyperplasia of the synovial lining and infiltration of inflammatory cells, primarily macrophages. Macrophages play a crucial role in the early inflammatory response through the production of several inflammatory cytokines, chemokines, growth factors, and proteinases. These pro-inflammatory mediators are activators of numerous signaling pathways that trigger other cytokines to further recruit more macrophages to the joint, ultimately leading to pain and disease progression. Very few therapeutic alternatives are available for treating inflammation in OA due to the condition's low self-healing capacity and the lack of clear diagnostic biomarkers. In this review, we opted to explore the immunomodulatory properties of mesenchymal stem cells (MSCs) and their paracrine mediators-dependent as a therapeutic intervention for OA, with a primary focus on the practicality of polarizing macrophages as suppression of M1 macrophages and enhancement of M2 macrophages can significantly reduce OA symptoms.


Subject(s)
Mesenchymal Stem Cells , Osteoarthritis , Humans , Osteoarthritis/metabolism , Inflammation/metabolism , Mesenchymal Stem Cells/metabolism , Macrophages/metabolism , Cytokines/metabolism
8.
J Gastroenterol Hepatol ; 37(10): 1991-1997, 2022 Oct.
Article in English | MEDLINE | ID: mdl-35738218

ABSTRACT

BACKGROUND AND AIM: Colonoscopy and fecal immunochemical test (FIT) are commonly used screening methods for the detection of colorectal cancer (CRC), but their effects on survival have not been compared. We compared survival outcomes in patients with CRC according to the exposure history to colonoscopy or FIT before diagnosis of CRC. METHODS: We performed a nationwide population-based retrospective cohort study using Korean national-insurance claims data. In total, 24 875 patients with CRC diagnosed in 2012 were included. The patients were divided into three groups in terms of examinations performed during the 10 years prior to CRC diagnosis: the colonoscopy group, the FIT group, and the never-screened group. Survival outcomes were compared among the three groups. The colonoscopy group and FIT group were matched using propensity score-matching method. RESULTS: The cohort consisted of 9619 patients in the colonoscopy group, 6936 patients in the FIT group, and 8320 patients in the never-screened group. The 5-year overall survival rates were 74.1% in the colonoscopy group, 65.9% in the FIT group, and 59.6% in the never-screened group (P < 0.001). The adjusted hazard ratios for death were 0.56 (95% confidence interval [CI], 0.53-0.59) in the colonoscopy group and 0.78 (95% CI, 0.74-0.82) in the FIT group compared with the never-screened group. In the matched cohort, the adjusted hazard ratios for death was 0.76 (95% CI, 0.72-0.81) in the colonoscopy group compared with the FIT group. CONCLUSION: Colonoscopy is a more effective method for reducing mortality in patients with CRC compared with FIT.


Subject(s)
Colorectal Neoplasms , Early Detection of Cancer , Colonoscopy , Colorectal Neoplasms/diagnosis , Early Detection of Cancer/methods , Feces , Humans , Mass Screening/methods , Occult Blood , Retrospective Studies
9.
Sci Rep ; 12(1): 4754, 2022 03 19.
Article in English | MEDLINE | ID: mdl-35306509

ABSTRACT

The immunomodulatory effects of mesenchymal stem cells (MSCs) on macrophages have been reported, however, the underlying mechanism remains unknown. Therefore, this study aimed to investigate the anti-inflammatory effects of MSCs on lipopolysaccharide (LPS)-stimulated macrophages and the subsequent downregulation of their inflammatory mediators. Macrophages were treated with conditioned media from MSCs, without a subsequent change of MSCs responding to the inflammation state. This study also evaluated whether the interleukin (IL) 4 stimulation of MSCs can improve their anti-inflammatory effects. Results demonstrated that the MSC-conditioned medium (MSC-CM) stimulated with IL4 significantly inhibited inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2) protein expression of LPS-activated macrophages. MSC-CM treatment inhibited the mRNA transcription of the cytokines IL1ß and IL6, the chemokines C-C motif ligand (CCL) 2, CCL3, CCL4, and CCL5, and the chemokine receptors CCR2 and CCR5, in LPS-stimulated macrophages. As revealed through western blot and immunofluorescence analyses, the phosphorylation of p38, JNK, and ERK MAPKs, as well as phosphorylation of NF-κB in stimulated macrophages, were also inhibited by the MSC-CM. Further, more potent anti-inflammatory effects were observed with the IL4-stimulated cells, compared with those observed with the non-stimulated cells. The MSC-CM demonstrated a potent anti-inflammatory effect on LPS-activated macrophages, while the IL4 stimulation improved this effect. These findings indicate that MSCs could exert anti-inflammatory effects on macrophages, and may be considered as a therapeutic agent in inflammation treatment.


Subject(s)
Lipopolysaccharides , Mesenchymal Stem Cells , Anti-Inflammatory Agents/metabolism , Anti-Inflammatory Agents/pharmacology , Culture Media, Conditioned/metabolism , Culture Media, Conditioned/pharmacology , Cyclooxygenase 2/metabolism , Humans , Inflammation/metabolism , Interleukin-4/metabolism , Lipopolysaccharides/metabolism , Lipopolysaccharides/pharmacology , Macrophages/metabolism , Mesenchymal Stem Cells/metabolism , NF-kappa B/metabolism , Nitric Oxide/metabolism , Nitric Oxide Synthase Type II/metabolism
10.
Medicine (Baltimore) ; 101(3): e28671, 2022 Jan 21.
Article in English | MEDLINE | ID: mdl-35060565

ABSTRACT

ABSTRACT: Early or multiple recurrences of symptomatic common bile duct (CBD) stones are troublesome late complications after endoscopic stone removal. We aimed to determine the factors related to early or multiple recurrences of CBD stones.We retrospectively analyzed patients who underwent endoscopic CBD stone extraction in a single institute between January 2006 and December 2015. Patients were divided into 2 groups according to the number and interval of CBD stone recurrences: single versus multiple (≥2) and early (<1.5 years) versus late (≥1.5 years) recurrence.After exclusion, 78 patients were enrolled and followed up for a median of 1974 (IQR: 938-3239) days. Twenty-seven (34.6%) patients experienced multiple recurrences (≥2 times), and 26 (33.3%) patients experienced early first recurrence (<1.5 years). In the multivariate analysis, CBD angulation was independently related to multiple CBD stone recurrence (OR: 4.689, P = .016), and endoscopic papillary large balloon dilation was independently related to late first CBD stone recurrence (OR: 3.783, P = .025). The mean CBD angles were more angulated with increasing instances of recurrence (0, 1, 2, 3, and ≥4 times) with corresponding values of 150.3°, 148.2°, 143.6°, 142.2°, and 126.7°, respectively (P = .011). The period between the initial treatment and first recurrence was significantly longer than the period between the first and second recurrence (P = .048).In conclusion, greater CBD angulation is associated with the increased number of CBD stone recurrence, and EPLBD delays the recurrence of CBD stones after endoscopic CBD stone removal.


Subject(s)
Cholangiopancreatography, Endoscopic Retrograde , Common Bile Duct/diagnostic imaging , Gallstones/surgery , Sphincterotomy, Endoscopic , Adult , Aged , Aged, 80 and over , Cholangiopancreatography, Endoscopic Retrograde/adverse effects , Common Bile Duct/surgery , Female , Humans , Male , Middle Aged , Recurrence , Retrospective Studies , Risk Factors , Treatment Outcome
11.
Front Bioeng Biotechnol ; 9: 734483, 2021.
Article in English | MEDLINE | ID: mdl-34692657

ABSTRACT

Bone morphogenetic proteins (BMPs) have been widely used as treatment for bone repair. However, clinical trials on fracture repair have challenged the effectiveness of BMPs and suggested that delivery of multipotent bone marrow stromal cells (BMSCs) might be beneficial. During bone remodeling and bone fracture repair, multipotent BMSCs differentiate into osteoblasts or chondrocytes to stimulate bone formation and regeneration. Stem cell-based therapies provide a promising approach for bone formation. Extensive research has attempted to develop adjuvants as specific stimulators of bone formation for therapeutic use in patients with bone resorption. We previously reported for the first time bone-forming peptides (BFPs) that induce osteogenesis and bone formation. BFPs are also a promising osteogenic factor for prompting bone regeneration and formation. Thus, the aim of the present study was to investigate the underlying mechanism of a new BFP-4 (FFKATEVHFRSIRST) in osteogenic differentiation and bone formation. This study reports that BFP-4 induces stronger osteogenic differentiation of BMSCs than BMP-7. BFP-4 also induces ALP activity, calcium concentration, and osteogenic factors (Runx2 and osteocalcin) in a dose dependent manner in BMSCs. Therefore, these results indicate that BFP-4 can induce osteogenic differentiation and bone formation. Thus, treatment of multipotent BMSCs with BFP-4 enhanced osteoblastic differentiation and displayed greater bone-forming ability than BMP-7 treatment. These results suggest that BFP-4-stimulated cell therapy may be an efficient and cost-effective complement to BMP-7-based clinical therapy for bone regeneration and formation.

12.
Saudi J Gastroenterol ; 27(5): 296-301, 2021.
Article in English | MEDLINE | ID: mdl-33642356

ABSTRACT

BACKGROUND: Endoscopic removal of large and thick-stalked pedunculated colonic polyps, often leads to massive hemorrhage. Several techniques to minimize this complication have not been widely adopted due to some caveats. In order to prevent postpolypectomy bleeding, we invented a novel technique to dissect long-stalked pedunculated colonic polyps using endoscopic band ligation (EBL) by laterally approaching the stalk. METHODS: In this prospective single-center study, 17 pedunculated polyps in 15 patients were removed between April 2012 and January 2016. We targeted pedunculated polyps with a long stalk length (>10 mm) and a large head (>10 mm) located in the distal colon. After identifying lesions with a colonoscope, we reapproached the middle part of the stalk of the targeted polyp with an EBL-equipped gastroscope to ligate it. Snare polypectomy was performed just above the ligation site of the stalk. RESULTS: EBL-assisted polypectomy removed all of the lesions successfully, which were confirmed pathologically. There was little technical difficulty associated with the endoscopic procedures, regardless of polyp size and stalk thickness, except for one case with a very large polyp that impeded the visualization of the ligation site. We observed a positive correlation between procedure time and the diameter of the head (spearman ρ = 0.52, P = 0.034). After dissection of the polyp, the EBL bands remained fastened to the dissected stalks in all cases. There was no complication associated with polypectomy for 1 month. CONCLUSION: EBL-assisted polypectomy is an easy, safe, and effective technique to remove long-stalked pedunculated colonic polyps without postpolypectomy bleeding.


Subject(s)
Colonic Polyps , Colon , Colonic Polyps/diagnostic imaging , Colonic Polyps/surgery , Colonoscopy , Humans , Pilot Projects , Prospective Studies
13.
Clin Endosc ; 53(3): 276-285, 2020 May.
Article in English | MEDLINE | ID: mdl-32506894

ABSTRACT

The area of endoscopic application has been continuously expanded since its introduction in the last century and the frequency of its use also increased stiffly in the last decades. Because gastrointestinal endoscopy is naturally exposed to diseased internal organs and contact with pathogenic materials, endoscopy mediated infection or disease transmission becomes a major concern in this field. Gastrointestinal endoscopy is not for single use and the proper reprocessing process is a critical factor for safe and reliable endoscopy procedures. What needed in these circumstances is a practical guideline for reprocessing the endoscope and its accessories which is feasible in the real clinical field to guarantee acceptable prevention of pathogen transmission. This guideline contains principles and instructions of the reprocessing procedure according to the step by step. And it newly includes general information and updated knowledge about endoscopy-mediated infection and disinfection. Multiple societies and working groups participated to revise; Korean Association for the Study of the Liver, the Korean Society of Infectious Diseases, Korean College of Helicobacter and Upper Gastrointestinal Research, the Korean Society of Gastroenterology, Korean Society of Gastrointestinal Cancer, Korean Association for the Study of Intestinal Diseases, Korean Pancreatobiliary Association, the Korean Society of Gastrointestinal Endoscopy Nurses and Associates and Korean Society of Gastrointestinal Endoscopy. Through this cooperation, we enhanced communication and established a better concordance. We still need more researches in this field and fill up the unproven area. And our guidelines will be renewed accordingly.

14.
Medicine (Baltimore) ; 99(23): e20539, 2020 Jun 05.
Article in English | MEDLINE | ID: mdl-32502013

ABSTRACT

Colon ischemia (CI) is the most common ischemic disorder of the gastrointestinal tract. Although some markers of CI, such as procalcitonin and alkaline phosphatase, have been reported, few specific serum markers have been identified. We investigated whether serum stromal cell-derived factor-1 (SDF-1) is a specific marker of CI and clarified the relationship between serum SDF-1 level and CI according to a history of combined chronic cardiovascular disease (CVD).We measured SDF-1 level and other serological markers in 84 patients (control, n = 20; CI without chronic CVD, n = 21; chronic CVD without CI, n = 20; CI with chronic CVD, n = 23).Patients with CI were older than those without CI. There were more women in the CI groups than those without CI. At admission, SDF-1 level was significantly higher in patients having CI with chronic CVD (P < .001) than in other groups. SDF-1 level was significantly higher at admission than at discharge in patients having CI with chronic CVD (P < .001) but not in patients having CI without chronic CVD. SDF-1 level did not differ according to symptoms, involved sites, or duration of hospitalization. At a cutoff value of 0.5 pg/mL for the SDF-1 level in patients having CI with chronic CVD, the sensitivity and specificity for SDF-1 were 91.3% and 95%, respectively. The area-under-the-curve (AUC) value was 0.95. In the logistic regression analysis, an elevation of the SDF-1 level to >0.5 pg/mL was a significant indicator of CI with chronic CVD [odds ratio (OR), 114.914; 95% confidence interval, 10.51 to >999.999; P < .001].SDF-1 could be a useful early biomarker for the diagnosis of CI in patients with chronic CVD.


Subject(s)
Cardiovascular Diseases/complications , Chemokine CXCL12/blood , Colon/blood supply , Ischemia/diagnosis , Aged , Alkaline Phosphatase/blood , Biomarkers/blood , Case-Control Studies , Chronic Disease , Creatine Kinase/blood , Female , Humans , L-Lactate Dehydrogenase/blood , Male , Middle Aged , Sensitivity and Specificity
15.
Biosci Biotechnol Biochem ; 84(9): 1861-1869, 2020 Sep.
Article in English | MEDLINE | ID: mdl-32475338

ABSTRACT

Dendritic cells (DCs) are play critical roles in the priming and regulation of immune responses. DCs rapidly process and convey these antigens to prime antigen-specific T cells. Therefore, regulation of DCs functions is important for immunity and immunotherapies. Immune adjuvants for DCs activation are needed to improve the efficacy of vaccines against tumors and many infectious diseases. Therefore, we demonstrate that H. fusiformis extract can regulate DCs maturation and activation. H. fusiformis extract induced costimulatory molecules (CD 80 and CD86), antigen-presenting molecules (major histocompatibility complex (MHC) I and II), CCR7 expression, and interleukin (IL)-12 production in DCs. These effects are associated with upregulation of mitogen-activated protein kinase (MAPK) signaling pathway. In addition, H. fusiformis extract induces costimulatory molecules on splenic DCs and activated CD8+ T cells in vivo. Taken together, these findings suggest that H. fusiformis extract may be a potential efficient immune therapeutic compound in DCs-mediated immunotherapies. ABBREVIATIONS: CTL: cytotoxic T lymphocytes; DCs: dendritic cells; ERK: extracellular signal-regulated kinases; IL: interleukini; JNK: c-Jun N-terminal kinase; MAPK: mitogen-activated protein kinase; MHC: major histocompatibility complex.


Subject(s)
Dendritic Cells/cytology , Dendritic Cells/drug effects , Plant Extracts/pharmacology , Sargassum/chemistry , Cell Differentiation/drug effects , Cell Line , Dendritic Cells/immunology , Dendritic Cells/metabolism , Gene Expression Regulation/drug effects , Humans , Interleukin-12/biosynthesis , Lymphocyte Activation/drug effects , MAP Kinase Signaling System/drug effects , Receptors, CCR7/metabolism
16.
Cancers (Basel) ; 12(5)2020 May 13.
Article in English | MEDLINE | ID: mdl-32414208

ABSTRACT

Triple-negative breast cancer (TNBC) refers to breast cancer that does not have receptors for estrogen, progesterone, and HER2 protein. TNBC accounts for 10-20% of all cases of breast cancers and is characterized by its metastatic aggressiveness, poor prognosis, and limited treatment options. Here, we show that the metastatic nature of TNBC is critically regulated by a functional link between miR-200a and the transcription factor ELK3. We found that the expression levels of miR-200a and the ELK3 mRNA were negatively correlated in the luminal and TNBC subtypes of breast cancer cells. In vitro experiments revealed that miR-200a directly targets the 3' untranslated region (UTR) of the ELK3 mRNA to destabilize the transcripts. Furthermore, ectopic expression of miR-200a impaired the migration and invasion of TNBC cells by reducing the expression level of the ELK3 mRNA. In in vivo studies, transfection of MDA-MB 231 cells (a claudin-low TNBC cell type) with exogenous miR-200a reduced their extravasation into the lung during 48 h after tail vein injection, and co-transfection of the cells with an expression plasmid harboring ELK3 that lacked an intact 3'UTR recovered their extravasation ability. Overall, our findings provide evidences that miR-200a and ELK3 is functionally linked to regulate invasive characteristics of breast cancers.

17.
Pathogens ; 9(4)2020 Apr 11.
Article in English | MEDLINE | ID: mdl-32290477

ABSTRACT

Surface disinfection in health-care facilities is critical to prevent dissemination of Clostridioides difficile (C. difficile). Tetracyclines (TCs) are broad-spectrum antibiotics that are associated with a low risk of development of C. difficile infection (CDI) and are used as photosensitizers (PS) in photodynamic therapy (PDT). We evaluated whether TCs may be useful environmental cleansing agents. We compared the in vitro ability to kill C. difficile of four TCs (TC, doxycycline, minocycline, and tigecycline) combined with PDT using ultraviolet A (UVA). We included chitosan, a cationic material, as a booster to increase the photodynamic bactericidal efficacy of TCs. PDT-induced bactericidal effects were assessed by the number of viable cells and the degree of DNA damage and membrane integrity. To avoid the intrinsic antibacterial activity of TCs at high concentrations, we used low concentrations of TCs (0.05 and 0.1 mg/mL). The bactericidal effect of treatment with chitosan plus PDT was over 100 times higher than that with PDT alone for each of the four TCs. DNA damage measured by ethidium bromide monoazide and real-time quantitative polymerase chain reaction was also greater for PDT plus chitosan treatment than for PDT alone or under control conditions: the threshold cycle (Ct) values for the control, PDT, and PDT plus chitosan were 14.67 ± 0.22, 20.46 ± 0.12, and 25.54 ± 0.17, respectively. All four TCs caused similar levels of severe cell membrane damage during PDT compared with control conditions. These data suggest that PDT combined with any of the four TCs plus chitosan might be an available tool to kill efficiently planktonic form of C. difficile.

18.
Cancer Res Treat ; 52(3): 714-721, 2020 Jul.
Article in English | MEDLINE | ID: mdl-32054151

ABSTRACT

PURPOSE: The purpose of this study was to investigate the diagnostic value of magnetic resonance imaging (MRI)-ultrasound (US) fusion transperineal targeted biopsy (FTB) and fusion template systematic biopsy (FSB) for prostate cancer (PCa) and clinically significant prostate cancer (csPCa) (intermediate/high grade [Gleason score ≥ 3+4]) based on bi-parametric MRI (bpMRI). MATERIALS AND METHODS: Retrospectively, we analyzed 300 patients with elevated prostate-specific antigen (≥ 4.0 ng/mL) and/or abnormal findings in a digital rectal examination at the Korea University Hospital. All 300 men underwent bpMRI-US fusion transperineal FTB and FSB in the period from April 2017 to March 2019. RESULTS: PCas were detected in 158 of 300 men (52.7%), and the prevalence of csPCa was 34.0%. CsPCas were detected in 12 of 102 (11.8%) with Prostate Imaging-Reporting and Data System (PI-RADS) 3, 42 of 92 (45.7%) with PI-RADS 4, respectively; and 45 of 62 (72.6%) men with PI-RADS 5, respectively. BpMRI showed a sensitivity of 95.1% and negative predictive value of 89.6% for csPCa. FTB detected additional csPCa in 33 men (12.9%) compared to FSB. Compared to FTB, FSB detected additional csPCa in 10 men (3.9%). CONCLUSION: BpMRI-US FTB and FSB improved detection of PCa and csPCa. The accuracy of bi-parametric MRI is comparable with that of multi-parametric MRI. Further, it is rapid, simpler, cheaper, and no side effects of contrast media. Therefore, it is expected that bpMRI-US transperineal FTB and FSB could be a good alternative to conventional US-guided transrectal biopsy, which is the current gold standard.


Subject(s)
Image-Guided Biopsy/methods , Magnetic Resonance Imaging/methods , Prostatic Neoplasms/diagnosis , Ultrasonography/methods , Aged , Follow-Up Studies , Humans , Male , Neoplasm Grading , Prostatic Neoplasms/diagnostic imaging , Prostatic Neoplasms/surgery , Retrospective Studies
20.
Clin Endosc ; 52(5): 443-450, 2019 Sep.
Article in English | MEDLINE | ID: mdl-31591281

ABSTRACT

A thorough disinfection and infection control process associated with gastrointestinal endoscopy is highly important for the health and safety of the examinee and the medical staff involved in the procedure. Endoscopic reprocessing and disinfection are two of the most important steps in quality control of endoscopy. In 2019, the Korean Society of Gastrointestinal Endoscopy updated the Accreditation of Qualified Endoscopy Unit assessment items for these quality indicators. Assessment of disinfection and infection control comprises 28 mandatory items in the categories of disinfection education, pre-cleaning, cleaning, disinfection, rinsing, drying, reprocessing, storage, endoscopic accessories, water bottle and connectors, space/facilities, personal protective equipment, disinfection ledger, and regulations regarding infection control and disinfection.
The updated Accreditation of Qualified Endoscopy Unit assessment items are useful for improving the quality of endoscopy by ensuring thorough inspection of endoscopic disinfection and infection control.

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