Aryl hydrocarbon receptor-targeted therapy for CD4+ T cell-mediated idiopathic pneumonia syndrome in mice.

We previously demonstrated that interferon γ (IFN-γ) derived from donor T cells co-opts the indoleamine 2,3-dioxygenase 1 (IDO1) → aryl hydrocarbon receptor (AHR) axis to suppress idiopathic pneumonia syndrome (IPS). Here we report that the dysregulated expression of AP-1 family genes in Ahr-/- lung epithelial cells exacerbated IPS in allogeneic bone marrow transplantation settings. AHR repressed transcription of Jund by preventing STAT1 from binding to its promoter. As a consequence, decreased interleukin-6 impaired the differentiation of CD4+ T cells toward Th17 cells. IFN-γ- and IDO1-independent induction of Ahr expression indicated that the AHR agonist might be a better therapeutic target for IPS than the IDO1 activator. We developed a novel synthetic AHR agonist (referred to here as PB502) that potently inhibits Jund expression. PB502 was highly effective at inducing AHR activation and ameliorating IPS. Notably, PB502 was by far superior to the endogenous AHR ligand, L-kynurenine, in promoting the differentiation of both mouse and human FoxP3+ regulatory CD4+ T cells. Our results suggest that the IDO1-AHR axis in lung epithelial cells is associated with IPS repression. A specific AHR agonist may exhibit therapeutic activity against inflammatory and autoimmune diseases by promoting regulatory T-cell differentiation.

15-Hydroxyprostaglandin dehydrogenase inhibitor prevents contrast-induced acute kidney injury.

The two primary mechanisms by which iodinated contrast media (CM) causes contrast-induced acute kidney injury (CIAKI) are the hemodynamic effect causing intrarenal vasoconstriction and the tubular toxic effect causing acute tubular necrosis. Inhibition of 15-hydroxyprostaglandin dehydrogenase (15-PGDH), which degrades prostaglandin E2 (PGE2), promotes tissue repair and regeneration in many organs. PGE2 causes intrarenal arterial vasodilation. In this study, we investigated whether a 15-PGDH inhibitor can act as a candidate for blocking these two major mechanisms of CIAKI. We established a CIAKI mouse model by injecting a 10 gram of iodine per body weight (gI/kg) dose of iodixanol into each mouse tail vein. A 15-PGDH inhibitor (SW033291), PGE1, or PGE2 were administered to compare the renal functional parameters, histologic injury, vasoconstriction, and renal blood flow changes. In addition, human renal proximal tubular epithelial cells were cultured in a CM-treated medium. SW033291, PGE1, or PGE2 were added to compare any changes in cell viability and apoptosis rate. CIAKI mice that received SW033291 had lower serum levels of creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule 1 (p < 0.001); lower histologic injury score and TUNEL positive rates (p < 0.001); and higher medullary arteriolar area (p < 0.05) and renal blood flow (p < 0.001) than CM + vehicle group. In cell culture experiments, Adding SW033291 increased the viability rate (p < 0.05) and decreased the apoptosis rate of the tubular epithelial cells (p < 0.001). This 15-PGDH inhibitor blocks the two primary mechanisms of CIAKI, intrarenal vasoconstriction and tubular cell toxicity, and thus has the potential to be a novel prophylaxis for CIAKI. Abbreviations: 15-PGDH: 15-hydroxyprostaglandin dehydrogenase; AMP: adenosine monophosphate; CIAKI: contrast-induced acute kidney injury; CM: contrast media; EP: prostaglandin E2 receptor; hRPTECs: human-derived renal proximal tubule epithelial cells; KIM-1: kidney injury molecule-1; MTT: 3-(4,5-Dimethyl thiazol-2-yl)-2,5-diphenyl tetrazolium bromide; NGAL: neutrophil gelatinase-associated lipocalin; PBS: phosphate-buffered saline; PGE1: prostaglandin E1; PGE2: prostaglandin E2; RBF: renal blood flow; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP nick-end labeling; α-SMA: α-Smooth muscle actin.

Inhibition of 15-PGDH prevents ischemic renal injury by the PGE2/EP4 signaling pathway mediating vasodilation, increased renal blood flow, and increased adenosine/A2A receptors.

In the present study, we demonstrated the marked activity of SW033291, an inhibitor of 15-hydoxyprostaglandin dehydrogenase (15-PGDH), in preventing acute kidney injury (AKI) in a murine model of ischemia-reperfusion injury. AKI due to ischemic injury represents a significant clinical problem. PGE2 is vasodilatory in the kidney, but it is rapidly degraded in vivo due to catabolism by 15-PGDH. We investigated the potential of SW033291, a potent and specific 15-PGDH inhibitor, as prophylactic treatment for ischemic AKI. Prophylactic administration of SW033291 significantly increased renal tissue PGE2 levels and increased post-AKI renal blood flow and renal arteriole area. In parallel, prophylactic SW033291 decreased post-AKI renal morphology injury scores and tubular apoptosis and markedly reduced biomarkers of renal injury that included blood urea nitrogen, creatinine, neutrophil gelatinase-associated lipocalin, and kidney injury molecule-1. Prophylactic SW033291 also reduced post-AKI induction of proinflammatory cytokines, high-mobility group box 1, and malondialdehyde. Protective effects of SW033291 were mediated by PGE2 signaling, as they could be blocked by pharmacological inhibition of PGE2 synthesis. Consistent with activation of PGE2 signaling, SW033291 induced renal levels of both EP4 receptors and cAMP, along with other vasodilatory effectors, including AMP, adenosine, and the adenosine A2A receptor. The protective effects of SW0333291 could largely be achieved with a single prophylactic dose of the drug. Inhibition of 15-PGDH may thus represent a novel strategy for prophylaxis of ischemic AKI in multiple clinical settings, including renal transplantation and cardiovascular surgery.

Activation of the alternative complement pathway predicts renal outcome in patients with lupus nephritis.

OBJECTIVES: The aims of this study were to clarify the activation of complement pathways in patients with lupus nephritis (LN), and to elucidate the association between these complement activation types and clinical outcomes. METHODS: We enrolled 115 patients with biopsy-proven LN from 2003 to 2016 from the lupus cohort at the Busan Paik Hospital and the Jeju National University Hospital in Korea. The patients were divided into two groups based on the patterns of glomerular complements deposits. The presence of C1q, C4 and/or C3 deposits in the glomerulus was considered evidence for the activation of the classical pathway with or without alternative pathway activation (group 1, N = 93), and glomerular C3 deposition without C1q and C4 deposits was considered as a marker for the alternative pathway limited activation (group 2, N = 22). The study end point was progression of kidney disease defined as a ≥50% reduction in estimated glomerular filtration rate from baseline values or advancement to end-stage renal disease. RESULTS: The mean estimated glomerular filtration rate and median urine protein-to-creatinine ratio of the patients were 85.7 ± 32.4 mL/min/1.73 m2 and 3.1 g/g, respectively, at the time of kidney biopsy. Forty-nine patients (43%) had nephrotic range of proteinuria. Compared to group 1 patients, those in group 2 were older, were more likely to be males and were more hypertensive. In addition, plasma C3 and C4 levels were significantly lower in group 1 patients compared to those in group 2. Moreover, anti-dsDNA concentration was significantly higher in group 1 patients compared to those in group 2. The mean follow-up time was 5.4 ± 3.4 years. The rates of response to one-year immunosuppressive treatment were poorer in group 2 patients compared to those in group 1. During the follow-up time, the progression of kidney disease was significantly higher in group 2 than in group 1 patients. CONCLUSION: This study showed that there was alternative complement pathway limited activation in the renal tissue in a small number of patients with LN, and these patients had worse renal outcomes compared to patients with glomerular classical complement pathway activation with or without alternative pathway activation.

Morphologic pattern analysis of submucosal deformities identified by endoscopic ultrasonography for predicting the depth of invasion in early gastric cancer.

BACKGROUND: The aims of this study are to evaluate the usefulness of submucosal deformity pattern analysis with endoscopic ultrasonography (EUS) for predicting the depth of invasion in early gastric cancer (EGC) and the treatment results of endoscopic submucosal dissection (ESD). METHODS: The endoscopic and EUS parameters of 345 patients with endoscopically suspected EGC who underwent endoscopic or surgical resection between July 2012 and May 2017 were retrospectively reviewed. All patients were classified into three categories as follows according to the morphologic type of submucosal deformity identified by EUS: (1) no submucosal deformity, (2) wedge-shaped deformity, and (3) arch-shaped deformity. The presence of an arch-shaped submucosal deformity on EUS and an active endoscopic ulcer or surrounding mucosal fold convergence/clubbing on conventional endoscopy were defined as suggestive of deep submucosal cancer invasion (SCI). RESULTS: Upper location (p = 0.034) and the presence of an arch-shaped submucosal deformity on EUS (p < 0.001) were significant predictors of deep submucosal invasion, with the presence of an arch-shaped submucosal deformity showing the highest predictive value (odds ratio of 26.27). The overall diagnostic accuracy of EUS for predicting deep SCI was 83.5%, with a sensitivity of 84.0% and a specificity of 83.3%, which were significantly higher than those of conventional endoscopy. A larger lesion size and the presence of an arch-shaped submucosal deformity were significant factors associated with noncurative resection after ESD. CONCLUSIONS: Submucosal deformity pattern analysis with EUS can provide more accurate information than conventional endoscopy for predicting deep SCI. The presence of an arch-shaped submucosal deformity on EUS was an effective predictor of deep SCI and noncurative resection.

The Significance of VSIG4 Expression in Ovarian Cancer.

OBJECTIVES: The protein V-set and Ig domain-containing 4 (VSIG4), a novel B7 family-related macrophage protein with the capacity to inhibit T-cell activation, has a potential role in cancer. Here we suggest its possibility as a therapeutic target and prognostic biomarker of ovarian cancer. METHODS: Between January 2011 and June 2015, tumor tissues and peripheral blood samples were obtained during surgery from 10 patients with benign ovarian tumors and 22 patients with ovarian cancers. Messenger RNA and protein expression levels of VSIG4 in benign tumor and cancer tissues were examined by the reverse transcription polymerase chain reaction and Western blot, respectively. Soluble VSIG4 concentrations were measured by an enzyme-linked immunosorbent assay. The correlation between VSIG4 expression and the prognosis of ovarian cancer was analyzed according to the patients' clinicopathologic characteristics. RESULTS: VSIG4 messenger RNA and protein expression levels in ovarian cancer tissues were higher than those in benign ovarian tumors (P = 0.0013 and 0.0001, respectively). Soluble VSIG4 concentrations were increased in patients with ovarian cancer compared with that in patients with benign ovarian tumors (P = 0.0452). Moreover, soluble VSIG4 levels were significantly increased in advanced-stage and recurrent ovarian cancer (P = 0.0244 and 0.0288, respectively). High VSIG4 expression of cancer tissue and low VSIG4 expression of plasma (soluble VSIG4) were associated with a longer disease-free interval (P = 0.0246 and 0.0398, respectively). CONCLUSIONS: VSIG4 is overexpressed in ovarian cancers compared with that in benign tumors. This finding supports VSIG4 being used as a potential therapeutic target for ovarian cancer. Furthermore, soluble VSIG4 levels are associated with the progression and recurrence of ovarian cancer, indicating that soluble VSIG4 may be used as a potential biomarker for predicting tumor prognosis.

Multifocal Kaposiform Hemangioendothelioma Causing Massive Fetal Chylous Ascites.

Kaposiform hemangioendothelioma (KHE) is a locally aggressive vascular tumor that usually occurs in soft tissues of the extremity and rarely in the retroperitoneum. We report a unique case of isolated massive fetal ascites attributed to KHE, involving the retroperitoneum and multiple visceral organs, along with the Kasabach-Merritt phenomenon. We suspect that retroperitoneal KHE might have caused massive fetal ascites because of its high potential to invade the lymphatic vessels aggressively in the retroperitoneal space, which possibly permits intestinal lymph leakage into the peritoneal cavities.

Pre- and post-ESD discrepancies in clinicopathologic criteria in early gastric cancer: the NECA-Korea ESD for Early Gastric Cancer Prospective Study (N-Keep).

BACKGROUND: Discrepancies in the clinicopathologic parameters pre- and post-endoscopic submucosal dissection (ESD) sometimes necessitate additional surgical resection. The aim of this study was to assess such discrepancies in clinicopathologic parameters before and after ESD in the context of reducing the risk of failure of curative ESD. METHODS: Data on 712 early gastric cancer patients were prospectively collected from 12 university hospitals nationwide. The inclusion criteria were differentiated carcinoma <3 cm in size, no ulceration, submucosal invasion <500 µm, and no metastasis. Clinicopathologic factors were compared retrospectively. RESULTS: The discrepancy rate was 20.1 % (148/737) and the most common cause of discrepancy was tumor size (64 cases, 8.7 %). Ulceration, undifferentiated histology, and SM2 invasion were found in 34 (4.6 %), 18 (2.4 %), and 51 cases (6.9 %), respectively. Lymphovascular invasion (LVI) was observed in 34 cases (4.6 %). Cases with lesions exceeding 3 cm in size showed more frequent submucosal invasion, an elevated gross morphology, and upper and middle locations (p < 0.05). In the cases with ulceration, depth of invasion (DOI) was deeper than in the cases without ulceration (p = 0.005). Differentiation was correlated with DOI and LVI (p = 0.021 and 0.007). DOI was correlated with tumor size, ulceration, differentiation, LVI, gross type, and location. There were statistically significant differences between mucosal cancer cases and submucosal cancer cases in tumor size, differentiation, ulceration, LVI, and location. CONCLUSIONS: The overall discrepancy rate was 20.1 %. To reduce this rate, it is necessary to evaluate the DOI very cautiously, because it is correlated with other parameters. In particular, careful checking for SM-invasive cancer is required due to the high incidence of LVI irrespective of the depth of submucosal invasion.

Predicting pre- and post-resectional histologic discrepancies in gastric low-grade dysplasia: A comparison of white-light and magnifying endoscopy.

BACKGROUND AND AIM: The aim of this study was to evaluate the validity of the parameters of conventional white-light endoscopy and magnifying endoscopy with narrow-band imaging (MENBI) for the prediction of discrepancies between pre- and post-resectional histology in cases of gastric adenoma with low-grade dysplasia (LGD) that were diagnosed based on endoscopically biopsied specimens. METHODS: The medical records of 266 lesions with gastric LGD that were diagnosed by endoscopic forceps biopsies were retrospectively reviewed. The Vienna classification was used for histologic diagnosis. These patients all underwent MENBI examinations followed by analyses of the incidence of histologic discrepancies and histologic heterogeneity. The relationship between white-light endoscopic/MENBI parameters and the presence of histologic discrepancies was also analyzed. RESULTS: Discrepancies between the pre- and post-resectional histologies were found in 74 cases (27.9%). Among those cases, the histology was upgraded in 71 cases, whereas the histology was downgraded in three cases. The presence of erythema and positive MENBI findings were independent factors for the prediction of upgraded histologic discrepancies (P-values = 0.008, < 0.001, respectively). A positive MENBI finding yielded the highest predictive value, with a multivariate adjusted odds ratio of 42.46. Histologic heterogeneity in post-resectional specimens was found in 40.8% of cases with upgraded histologic discrepancies. CONCLUSIONS: MENBI can provide more accurate information than white-light endoscopy for the prediction of pre- and post-resectional histologic discrepancies in biopsy-proven gastric LGD. Endoscopic resection is strongly recommended in cases with surface erythema on conventional white-light endoscopy or positive MENBI, irrespective of the lesion size.

Caffeic acid phenethyl ester lessens disease symptoms in an experimental autoimmune uveoretinitis mouse model.

Experimental autoimmune uveoretinitis (EAU) is an autoimmune disease that models human uveitis. Caffeic acid phenethyl ester (CAPE), a phenolic compound isolated from propolis, possesses anti-inflammatory and immunomodulatory properties. CAPE demonstrates therapeutic potential in several animal disease models through its ability to inhibit NF-κB activity. To evaluate these therapeutic effects in EAU, we administered CAPE in a model of EAU that develops after immunization with interphotoreceptor retinal-binding protein (IRBP) in B10.RIII and C57BL/6 mice. Importantly, we found that CAPE lessened the severity of EAU symptoms in both mouse strains. Notably, treated mice exhibited a decrease in the ocular infiltration of immune cell populations into the retina; reduced TNF-α, IL-6, and IFN-γ serum levels: and inhibited TNF-α mRNA expression in retinal tissues. Although CAPE failed to inhibit IRBP-specific T cell proliferation, it was sufficient to suppress cytokine, chemokine, and IRBP-specific antibody production. In addition, retinal tissues isolated from CAPE-treated EAU mice revealed a decrease in NF-κB p65 and phospho-IκBα. The data identify CAPE as a potential therapeutic agent for autoimmune uveitis that acts by inhibiting cellular infiltration into the retina, reducing the levels of pro-inflammatory cytokines, chemokine, and IRBP-specific antibody and blocking NF-κB pathway activation.

T4 stage and preoperative anemia as prognostic factors for the patients with colon cancer treated with adjuvant FOLFOX chemotherapy.

BACKGROUND: FOLFOX-based adjuvant chemotherapy is a benefit for high-risk stage II and stage III colon cancer after curative resection. But, the prognostic factor or predictive marker for the efficacy of FOLFOX remains unclear. This study was aimed to identify the prognostic value and cumulative impact of adjuvant FOLFOX on the stage II and III colon cancer patients. METHODS: A total of 196 stage II and III colon cancer patients were retrospectively enrolled in prospectively collected data. They underwent curative resection followed by FOLFOX4 adjuvant chemotherapy. The oncological outcomes included the 5-year disease-free survival (DFS) rate and 5-year overall survival (OS) rate. Cox-regression analysis was performed to identify the prognostic value, and its cumulative impact was analyzed. RESULTS: The 5-year DFS rate of the patients was 71.94% and the 5-year OS rate was 81.5%. The prognostic values for the 5-year DFS rate and 5-year OS rate were T4 stage and preoperative anemia in a multivariate analysis. Each patient group who had no prognostic value, single, or both factors revealed 95.35%, 69.06%, and 28.57% in the 5-year DFS rate, respectively (p < 0.0001). The 5-year OS rate also showed the significant differences in each group who had no prognostic value, single, or both factors revealed 100%, 79.3%, and 45.92%, respectively (p < 0.0001). CONCLUSION: Our results showed similar efficacy to MOSAIC study in stage II and stage III colon cancer patients treated with adjuvant FOLFOX chemotherapy after curative resection. Patients who had T4 stage and/or preoperative anemia showed worse prognosis than patients without any prognostic value. These findings suggest that FOLFOX could not be effective in the patients with T4 stage colon cancer accompanied by preoperative anemia.

Intratumoral heterogeneity impacts the response to anti-neu antibody therapy.

BACKGROUND: Along with de novo resistance, continued exposure to trastuzumab, an anti-human epidermal growth factor receptor 2 (HER2/neu) antibody, can lead to acquired resistance. In this study, we characterize a new anti-HER2/neu antibody resistant and metastatic mouse breast carcinoma cell line, TUBO-P2J. This cell line was developed during in vivo experiments using the antibody sensitive and non-metastatic tumor line TUBO. In addition, TUBO-P2J was used to establish an intratumoral HER2 heterogenous animal tumor model to evaluate the therapeutic effects of anti-HER2/neu antibody. METHODS: After establishing the cell line, TUBO-P2J was characterized regarding its susceptibility to anti-neu antibody and chemotherapeutics, as well as its metastatic potential in vitro and in vivo. In addition, expression profiles of metastasis related genes were also evaluated. A clinically relevant intratumoral HER2 heterogenous tumor model was established by inoculating mice with tumor cells consisting of TUBO and TUBO-P2J at a ratio of 1,000:1 or 10,000:1. Tumor growth and mouse survival were used to evaluate the therapeutic effects of anti-neu antibody. RESULTS: The TUBO-P2J cell line is a HER2/neu negative and highly metastatic variant of TUBO. This cell line was resistant to anti-neu antibody therapy, and when inoculated subcutaneously, metastasized to the lungs within 14 days. Compared to the parental TUBO cell line, TUBO-P2J displayed an epithelial-mesenchymal transition (EMT) related gene expression profile including: the loss of E-cadherin, and increased Vimentin, Snail, and Twist1 expression. In addition, TUBO-P2J exhibited increased invasion and migration activity, and was resistant to chemotherapy drugs. Finally, mixed tumor implantations experiments revealed that an increased percentage of TUBO-P2J rendered tumors less responsive to anti-neu antibody therapy. CONCLUSION: This study describes a novel model of intratumoral heterogenous metastatic breast cancer in immune competent mice that can be used to develop novel or combined immunotherapies to overcome antibody resistance.

Cold tolerance in Campylobacter jejuni and its impact on food safety.

Campylobacter jejuni is a major cause of foodborne illnesses worldwide and is primarily transmitted to humans through contaminated poultry meat. To control this pathogen, it is critical to understand its cold tolerance because poultry products are usually distributed in the cold chain. However, there is limited information regarding how this thermotolerant, microaerophilic pathogen can survive in cold and aerobic environments in the poultry cold chain. In this study, we investigated the cold tolerance of C. jejuni by measuring the viability of 90 C. jejuni strains isolated from retail raw chicken at 4 °C under aerobic and microaerobic conditions. Despite the microaerophilic nature of C. jejuni, under aerobic conditions, C. jejuni exhibited higher viability at 4 °C and required an extended inactivation time compared to microaerobic conditions. Some strains were highly tolerant to refrigeration temperatures and exhibited increased survival at 4 °C. These cold-tolerant strains mostly belonged to multilocus sequence typing (MLST) clonal complex (CC)-21 and CC-443, indicating that cold tolerance is associated with the phylogeny of C. jejuni. Notably, cold-tolerant strains had an increased probability of illness and were more likely to cause human infections due to their extended survival on refrigerated chicken meat compared to those sensitive to cold stress. Furthermore, the majority of cold-tolerant strains exhibited elevated aerotolerance, indicating that cold tolerance is related to aerotolerance. These findings suggest that refrigeration of chicken meat under aerobic conditions may not be effective at controlling C. jejuni and that cold-tolerant C. jejuni can pose an increased risk to food safety.

Tuberculous Pericarditis Mimicking a Malignant Pericardial Tumor: A Case Report.

Tuberculous pericarditis is an extrapulmonary manifestation of tuberculosis that is most commonly associated with pericardial thickening, effusion, and calcification. We present a case of tuberculous pericarditis mimicking a malignant pericardial tumor in a 77-year-old male. CT revealed an irregular and nodular pericardial thickening. MRI revealed high signal intensity on T1-weighted fat-suppressed images and peripheral rim enhancement after gadolinium administration. MRI can be helpful in determining the differential diagnoses in cases of tuberculous pericarditis with nonspecific imaging findings.

Impact of nonspecific allograft biopsy findings in symptomatic kidney transplant recipients.

A for-cause biopsy is performed to diagnose the cause of allograft dysfunction in kidney transplantation. We occasionally encounter ambiguous biopsy results in symptomatic kidney transplant recipients. Yet, the allograft survival outcome in symptomatic recipients with nonspecific allograft biopsy findings remains unclear. The purpose of this study was to analyze the impact of nonspecific for-cause biopsy findings in symptomatic kidney transplant recipients. We retrospectively collected records from 773 kidney transplant recipients between January 2008 and October 2021. The characteristics of transplant recipients with nonspecific findings in the first for-cause biopsy were analyzed. Nonspecific allograft biopsy findings were defined as other biopsy findings excluding rejection, borderline rejection, calcineurin inhibitor toxicity, infection, glomerulonephritis, and diabetic nephropathy. The graft outcome was compared between recipients who had never undergone a for-cause biopsy and those who had a first for-cause biopsy with nonspecific findings. The graft survival in recipients with nonspecific for-cause biopsy findings was comparable to that in recipients who did not require the for-cause biopsy before and after propensity score matching. Even in symptomatic kidney transplant recipients, nonspecific allograft biopsy findings might not be a poor prognostic factor for allograft survival compared to recipients who did not require the for-cause biopsy.

Glomerulonephritis following COVID-19 infection or vaccination: a multicenter study in South Korea.

BACKGROUND: Despite the widespread impact of the severe acute respiratory syndrome coronavirus 2 (coronavirus disease 2019, COVID-19) and vaccination in South Korea, our understanding of kidney diseases following these events remains limited. We aimed to address this gap by investigating the characteristics of glomerular diseases following the COVID-19 infection and vaccination in South Korea. METHODS: Data from multiple centers were used to identify de novo glomerulonephritis (GN) cases with suspected onset following COVID-19 infection or vaccination. Retrospective surveys were used to determine the COVID-19-related histories of patients who were initially not implicated. Bayesian structural time series and autoregressive integrated moving average models were used to determine causality. RESULTS: Glomerular diseases occurred shortly after the infection or vaccination. The most prevalent postinfection GN was podocytopathy (42.9%), comprising primary focal segmental glomerulosclerosis and minimal change disease, whereas postvaccination GN mainly included immunoglobulin A nephropathy (IgAN; 57.9%) and Henoch-Schönlein purpura nephritis (HSP; 15.8%). No patient progressed to end-stage kidney disease. Among the patients who were initially not implicated, nine patients with IgAN/HSP were recently vaccinated against COVID-19. The proportion of glomerular diseases changed during the pandemic in South Korea, with an increase in acute interstitial nephritis and a decrease in pauci-immune crescentic GN. CONCLUSION: This study showed the characteristics of GNs following COVID-19 infection or vaccination in South Korea. Understanding these associations is crucial for developing effective patient management and vaccination strategies. Further investigation is required to fully comprehend COVID-19's impact on GN.

Indication for endoscopic treatment of ulcerative early gastric cancer according to depth of ulcer and morphological change.

BACKGROUND AND AIM: This study was conducted to determine the clinicopathologic factors affecting the stage of ulcerative early gastric cancer (EGC), focusing on the relationships between cancer stage and degree of endoscopic ulcer depth and morphologic changes. METHODS: Medical records of 183 cases of ulcerative EGC who had received endoscopic examination two or more times with a minimum interval of one week, and who underwent either curative surgery or endoscopic treatment were retrospectively reviewed. RESULTS: Change in ulcer morphology at follow-up endoscopy was observed in 84 cases (45.9%) with improvement and exacerbation of ulcer in 65 (35.5%) and 19 (13.8%) cases, respectively. The presence of type III ulcer (P < 0.01), and endoscopic findings suggesting submucosal cancer invasion (tumorous bank, fusion of converging folds, hardness or decreased flexibility) (P < 0.01), and incomplete ulcer healing (P = 0.036) were independently associated with a higher incidence of submucosal cancer invasion. The incidence of lymph node metastasis was 14.1%, and undifferentiated histology and presence of lymphovascular invasion were significantly associated with a higher incidence of lymph node metastasis (P = 0.018 and P = 0.005, respectively). CONCLUSIONS: Endoscopic resection with curative intent may be an acceptable option for EGC combined with endoscopic ulcer or ulcer scar, but should be restricted to cases showing significant improvement in the size and depth of ulcer at follow-up endoscopy, and which are not accompanied with deep ulcer more than the thickness of adjacent mucosal surface and prominent surrounding mucosal fold change. In addition, histologic criteria should meet the conditions of differentiated intramucosal cancer without lymphovascular invasion.

Fibrillary glomerulonephritis associated with Behçet's syndrome.

Fibrillary glomerulonephritis (FGN) is a rare cause of progressive renal dysfunction resulting in fibrillary deposits in the mesangium and/or glomerular basement membrane (GBM). Some case reports have shown FGN in patients with rheumatoid arthritis and other autoimmune diseases. This is the first case report of FGN in a patient with Behçet's syndrome. The most common renal histological finding in Behçet's syndrome is secondary amyloidosis. A 46-year-old woman with a 4-year history of Behçet's syndrome was referred to the nephrology clinic with foamy urine with non-selective proteinuria (urine protein-to-creatinine ratio was 1400 mg protein/g creatinine) and microscopic hematuria. Serum and urine protein electrophoresis showed no evidence of monoclonal gammopathy. A renal biopsy was performed. Light microscopy showed mesangial widening and nodular expansion with hyaline deposits. Immunofluorescence microscopy revealed immunoglobulin M deposits in the mesangium. Congo red staining was negative. Electron microscopy showed fibrillary deposits on the GBM. Pathological findings were consistent with FGN. She had been taking 50 mg azathioprine and 3000 mg mesalazine per day for 4 years due to Behçet's syndrome, so we did not add any other immunosuppressive agents or corticosteroids. Treatment of this glomerulopathy is not promising. It has been noted that none of the various approaches, including corticosteroid, plasmapheresis, and cytotoxic therapy, improves prognosis.

15-Prostaglandin Dehydrogenase Inhibition Enhances Colon Cancer Metastasis by Up-regulation of Epithelial-to-Mesenchymal Transition Genes.

BACKGROUND/AIM: Most deaths from colon cancer are due to metastasis. Recently, PGE2 was found to influence colon cancer invasion and metastasis. 15-PGDH, an enzyme that metabolizes PGE2, is known as a tumor suppressor in colonic carcinogenesis. This study investigated the effect of 15-PGDH on colon cancer metastasis. MATERIALS AND METHODS: 15-PGDH expression by immunohistochemical staining, clinicopathologic features, and 5-year cancer-specific survival were investigated in colon cancer patients. Liver metastasis was examined by assaying 15-PGDH activity in an animal model. Changes in PGE2, proliferation, migration, and invasion of the colorectal cancer cell line HCT116, were examined using a 15-PGDH inhibitor (SW033291) or enhancer (CDDO-ME). The expression of genes involved in the epithelial-to-mesenchymal transition (EMT) was also studied. RESULTS: The absence of 15-PGDH expression significantly correlated with advanced-stage, lymph node metastasis, and decreased cancer-specific survival in colon cancer patients. Inhibition of 15-PGDH increased colon cancer liver metastasis in the animal model. The 15-PGDH inhibitor, SW033291, increased PGE2 and decreased 15-PGDH expression on HCT116. However, treatment with CDDO-ME, a substance that enhances 15-PGDH, showed the opposite results. Inhibition of 15-PGDH increased cell proliferation, migration, and invasion, but activation of 15-PGDH showed the opposite effect. Inhibition of 15-PGDH also affected the EMT markers, N-cadherin, Snail, and Twist2. CONCLUSION: 15-PGDH inhibition increased colon cancer metastasis by inducing changes in EMT-related genes via an increase in PGE2 expression and could be a promising biomarker for anticancer treatment.

Expression of galectin-9 by IFN-γ stimulated human nasal polyp fibroblasts through MAPK, PI3K, and JAK/STAT signaling pathways.

Galectin-9 exhibited potent and selective eosinophil chemoattractant activity and attracted eosinophils in vitro and in vivo. Nasal polyposis is a chronic inflammatory disease of the upper airway characterized by the marked presence of inflammatory cells, particularly eosinophils. Thus, galectin-9 may be implicated in the pathogenesis of nasal polyposis. The study was designed to investigate whether interferon-gamma (IFN-γ) can induce the augmentation of galectin-9 expression and induce the expression of galectin-9 in nasal polyps. We examined the correlation between galectin-9 expression and eosinophil infiltration in nasal polyps. In addition, we identified the signaling pathways involved in the elevation of galectin-9 expression in response to IFN-γ. Our data demonstrate that the involvement of mitogen-activated protein kinases (MAPKs), phosphatidylinositol 3 phosphate kinase (PI3K), and Janus kinase/signal transducer and activator of transcription (JAK/STAT) may play important roles in the selective recruitment of eosinophils in nasal polyp tissues through the production of galectin-9. These findings suggest that galectin-9 expression is associated with eosinophil infiltration in polyps of patients with nasal polyposis.