A Case Report of MPO-ANCA-Associated Vasculitis Following Heterologous mRNA1273 COVID-19 Booster Vaccination.

Despite that clinical trials have been examining the safety profile of coronavirus disease 2019 (COVID-19) vaccines, there are concerns about long-term side effects as the number of vaccinations increases. Herein, we report a case of new-onset renal-limited anti-myeloperoxidase (MPO) antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis after booster vaccination with the mRNA 1273 (Moderna) vaccine. A 72-year-old woman with no specific past history, and who had a normal renal function, developed ANCA-associated vasculitis following heterologous booster with mRNA1273 (Moderna) vaccine. After a kidney biopsy, she was diagnosed with ANCA-associated pauci-immune crescentic glomerulonephritis. Her renal function and constitutional symptoms have been improved with treatment with plasmapheresis, intravenous cyclophosphamide and steroid pulse therapy (intravenous 500 mg of methylprednisolone sodium succinate for 3 days) followed by a reduced steroid regimen.

Temperature-Dependent Evolution of Poly(3-Hexylthiophene) Type-II Phase in a Blended Thin Film.

The structure of P3HT in P3HT:PCBM films is examined on a poly(3,4-ethylenedioxythiophene) polystyrene sulfonate ( PEDOT: PSS) substrate subjected to cryo-cooling to low temperature (-143 °C) followed by gradual heating to 50 °C. The behavior of these systems is examined in the absence and presence of an Al electrode on top of the P3HT:PCBM film. At temperatures below -10 °C, only the type-I phase of P3HT is observed. However, the type-II phase of P3HT starts to form near -10 °C, in both the presence and absence of the Al layer. In the system without an Al layer, the type-II phase disappears at 30 °C, but this phase persists to 50 °C in the presence of the Al layer. Concomitant with the formation of the type-II phase, a 1:3 ordered P3HT type-II (1/3,0,0) superlattice peak emerged. The type-II domains tend to form near the Al electrode layer and show a higher degree of alignment than the type-I crystals.

Dioxinodehydroeckol Enhances the Differentiation of Osteoblasts by Regulating the Expression of Phospho-Smad1/5/8.

Lack of bone formation-related health problems are a major problem for the aging population in the modern world. As a part of the ongoing trend of developing natural substances that attenuate osteoporotic bone loss conditions, dioxinodehydroeckol (DHE) from edible brown alga Ecklonia cava was tested for its effects on osteoblastogenic differentiation in MC3T3-E1 pre-osteoblasts. DHE was observed to successfully enhance osteoblast differentiation, as indicated by elevated cell proliferation, alkaline phosphatase activity, intracellular cell mineralization, along with raised levels of osteoblastogenesis indicators at the concentration of 20 µM. Results suggested a possible intervening of DHE on the bone morphogenetic protein (BMP) signaling pathway, according to elevated protein levels of BMP-2, collagen-I, and Smads. In addition, the presence of DHE was also able to raise the phosphorylated extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) levels which are also activated by the BMP signaling pathway. In conclusion, DHE is suggested to be a potential bioactive compound against bone loss that could enhance osteoblastogenesis with a suggested BMP pathway interaction.

Radical scavenging and anti-inflammatory effects of the halophyte Spergularia marina Griseb.

As a part of ongoing research to develop antioxidant and anti-inflammatory nutraceuticals, an ethanolic extract of Spergularia marina Griseb. was tested for its ability to scavenge radicals and suppress inflammation. The extract was able to scavenge 1,1-diphenyl-2-picrylhydrazyl (DPPH), hydroxyl, and superoxide radicals, respectively, in cell-free environments as well as intracellular radicals in H2O2-stimulated mouse macrophages. Inflammation in mouse macrophages induced by lipopolysaccharides was suppressed by S. marina according to the measurement of nitric oxide generation and expression of inflammatory cytokines, i.e. tumour necrosis factor-α (TNFα), interleukin (IL)-1ß, and IL-6. The anti-inflammatory effect of S. marina was substantiated by the finding that the expression of the inflammatory modulators, inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2), was significantly decreased. The chemical composition of S. marina was evaluated by FT-IR analysis of the extract indicating the presence of polyphenols and flavonoids. In conclusion, S. marina is suggested as a novel source for antioxidant and anti-inflammatory agents.

Endothelial marker profiles in cerebral radiation-induced vasculopathy: A comparative immunohistochemical analysis.

Radiation therapy results in radiation-induced vasculopathy, characterized by alterations in the vascular architecture stemming from radiation exposure. The exact molecular pathways and associated pathologies of this condition have yet to be comprehensively understood. This study aimed to identify specific markers' roles in cerebral vascular endothelial injury pathogenesis after radiosurgery and explore their unique expression patterns in diverse pathologies post-stereotactic radiosurgery. A retrospective cohort study was conducted to assess the expression profiles of endothelial markers via immunohistochemical analysis in 25 adult patients (13 males and 12 females) who had undergone neurosurgical resection for various central nervous system pathologies following stereotactic radiosurgery or radiotherapy from 2001 to 2015. Our findings revealed strong immunohistochemical expression of ICAM-1 and E-selectin across various disease states, while MMP-9, PAI-1, and eNOS exhibited moderate expression levels. In contrast, VCAM-1 and P-Selectin had the weakest expression across all groups. Notably, while individual markers showed significant variations in expression levels when comparing different diseases (P < .001), no substantial differences were found in the overall immunohistochemical expression patterns across the 5 distinct pathologies studied (P = .407, via 2-way ANOVA). Despite the varied long-term effects of radiotherapy on the vascular endothelium, a common thread of inflammation runs through the pathology of these conditions. The distinct patterns of marker expression identified in our study suggest that different markers play unique roles in the development of radiation-induced vasculopathy. These findings offer insights that could lead to the development of novel preventive strategies and treatments.

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.

Primary Bilateral Tuberculous Otitis Media After Kidney Transplantation: A Case Report.

We report a case of primary bilateral tuberculous otitis media in a patient who underwent kidney transplantation. This case presents unusual clinical features and histopathology from those of classical tuberculous otitis media. A 75-year-old woman presented at the clinic with purulent ear discharge and hearing loss in both ears. She had undergone kidney transplantation 6 years prior and had been taking immunosuppressant medications. Otoscopic examination and imaging studies suggested acute otitis media, which was irresponsive to antibiotics. The patient underwent surgery to eradicate the disease, and histopathologic examination revealed multifocal granulomas with Langhans giant cells without caseous changes. Ziehl-Neelsen staining and polymerase chain reaction confirmed the diagnosis of tuberculous otitis media. While tuberculous otitis media is a very rare manifestation of extrapulmonary tuberculosis, this case is more noteworthy in that it occurred as a primary infection rather than as a reactivation of a prior infection. In addition, it did not show the classical triad of clinical manifestations, which occurred bilaterally, and its histopathology was different from those of classical tuberculous otitis media. This case presents a new clinical variation in tuberculous otitis media.

A rare case of endobronchial melanoma of unknown primary.

A 62-year-old man who presented with complaints of cough and hemoptysis was found to have an endobronchial tumor which obstructed the lingular bronchus. Histopathologic examination of a bronchoscopic biopsy of the tumor was consistent with malignant melanoma. Skin, mucosal, and eye examinations failed to detect the primary site of melanoma and the patient was diagnosed with endobronchial melanoma of unknown primary (MUP). Although the patient underwent a curative surgical resection, recurrence was detected in 4 months. Endobronchial MUP is a rare presentation of melanoma and better therapeutic strategies need to be established.

The Role of V-Set Ig Domain-Containing 4 in Chronic Kidney Disease Models.

V-set Ig domain-containing 4 (VSIG4) regulates an inflammatory response and is involved in various diseases. However, the role of VSIG4 in kidney diseases is still unclear. Here, we investigated VSIG4 expression in unilateral ureteral obstruction (UUO), doxorubicin-induced kidney injury mouse, and doxorubicin-induced podocyte injury models. The levels of urinary VSIG4 protein significantly increased in the UUO mice compared with that in the control. The expression of VSIG4 mRNA and protein in the UUO mice was significantly upregulated compared with that in the control. In the doxorubicin-induced kidney injury model, the levels of urinary albumin and VSIG4 for 24 h were significantly higher than those in the control mice. Notably, a significant correlation was observed between urinary levels of VSIG4 and albumin (r = 0.912, p < 0.001). Intrarenal VSIG4 mRNA and protein expression were also significantly higher in the doxorubicin-induced mice than in the control. In cultured podocytes, VSIG4 mRNA and protein expressions were significantly higher in the doxorubicin-treated groups (1.0 and 3.0 µg/mL) than in the controls at 12 and 24 h. In conclusion, VSIG4 expression was upregulated in the UUO and doxorubicin-induced kidney injury models. VSIG4 may be involved in pathogenesis and disease progression in chronic kidney disease models.

A Flexible Piezoelectric Device for Frequency Sensing from PVDF/SWCNT Composite Fibers.

Polymer piezoelectric devices have been widely studied as sensors, energy harvesters, and generators with flexible and simple processes. Flexible piezoelectric devices are sensitive to external stimuli and are attracting attention because of their potential and usefulness as acoustic sensors. In this regard, the frequency sensing of sound must be studied to use flexible piezoelectric devices as sensors. In this study, a flexible piezoelectric device composed of a polymer and an electrode was successfully fabricated. Polyvinylidene fluoride, the active layer of the piezoelectric device, was prepared by electrospinning, and electrodes were formed by dip-coating in a prepared single-walled carbon nanotube dispersion. The output voltage of the external sound was matched with the input frequency through a fast Fourier transform, and frequency matching was successfully performed, even with mechanical stimulation. In a high-frequency test, the piezoelectric effect and frequency domain peak started to decrease sharply at 300 Hz, and the limit of the piezoelectric effect and sensing was observed from 800 Hz. The results of this study suggest a method for developing flexible piezoelectric-fiber frequency sensors based on piezoelectric devices for acoustic sensor systems.

Biochemical characterization of the two novel mgCas12a proteins from the human gut metagenome.

CRISPR/Cas9 and Cas12a belonging to the Class II CRISPR system are characterized by a single-component effector protein. Despite unique features of Cas12a like DNA cleavage with 5' staggered ends and a single crRNA, Cas12a has not been adopted in biotechnological applications to the similar extent as Cas9. To better understand the CRISPR/Cas12 systems, we selected two candidates, designated mgCas12a-1 and mgCas12a-2, from an analysis of the human microbiome metagenome (mg) and provided biochemical characterization. These new Cas12a proteins shared about 37% identity in amino acid sequences and shared the same direct repeat sequences in the crRNA with FnCas12a from Francisella novicida. The purification yield of the recombinant proteins was up to 3.6-fold greater than that of FnCas12a. In cell-free DNA cleavage assays, both mgCas12a proteins showed the higher cleavage efficiencies when Mn2+ was provided with KCl (< 100 mM) than tested other divalent ions. They were able to tolerate ranges of pH points and temperature, and showed the highest cleavage efficiencies at pH 8.0 and 50 °C. In addition, mgCas12a proteins showed 51% less crRNA-independent and 56% less crRNA-dependent non-specific nuclease activity upon prolonged incubation than did FnCas12a. Considering their greater yield in protein preparation and reduced non-specific nuclease activity, our findings may expedite the use of Cas12a especially when genome editing needs to be practiced with the form of ribonucleoproteins.

Synthesis and drug release properties of melanin added functional allopurinol incorporated starch-based biomaterials.

The main objective of this study was to prepare functional allopurinol (ALP) incorporated biomaterials using mungbean starch, polyvinyl alcohol, melanin (MEL), and plasticizers. Prepared biomaterials were characterized by FE-SEM and FT-IR analysis. Photothermal conversion efficiencies and ALP release properties of biomaterials were evaluated with NIR laser irradiation. When biomaterials were irradiated with the NIR laser, temperatures increase of MEL-added biomaterials were higher than those of MEL-non-added biomaterials. After NIR laser irradiation, ALP release rates of MEL-added biomaterials were 1.62 times faster than those of MEL-non-added biomaterials. In addition, ALP release using an artificial skin was increased by NIR laser irradiation. ALP release from biomaterials followed Fickian diffusion mechanism, while ALP release using an artificial skin followed a non-Fickian diffusion mechanism. Xanthine oxidase inhibitory (%) for MEL-added biomaterials with/without the addition of GL and XL were 47.5%, 61.7%, and 65.1%, respectively.

Upregulation of VSIG4 in Type 2 Diabetic Kidney Disease.

Fibrosis is the final common finding in patients with advanced diabetic kidney disease. V-set Ig domain containing 4 (VSIG4) is related to fibrosis in several diseases. It also contributes to fibrosis under high-glucose conditions in renal tubule cells. To determine the role of VSIG4 in type 2 diabetes, we examined VSIG4 expression in a type 2 diabetic animal model and podocyte. Urinary excretion of albumin and VSIG4 was significantly higher in db/db mice than in the control group. Urine VSIGs levels for 6 h were about three-fold higher in db/db mice than in db/m mice at 20 weeks of age: 55.2 ± 37.8 vs. 153.1 ± 74.3 ng, p = 0.04. Furthermore, urinary VSIG4 levels were significantly correlated with urinary albumin levels (r = 0.77, p < 0.01). Intrarenal VSIG4 mRNA expression was significantly higher in db/db mice than in control mice (1.00 ± 0.35 vs. 1.69 ± 0.77, p = 0.04). Further, VSIG4 expression was almost twice as high in db/db mice at 20 weeks of age. Intrarenal VSIG immunoreactivity in db/db mice was also significantly higher than that in control mice. In cultured podocytes, both high glucose and angiotensin II significantly upregulated the expression of VSIG4 mRNA and protein. In conclusion, VSIG4 was upregulated in an animal model of type 2 diabetes and was related to albuminuria and pro-fibrotic markers. Considering these relationships, VSIG4 may be an important mediator of diabetic nephropathy progression.

Bioimaging for the monitoring of the in vivo distribution of infused mesenchymal stem cells in a mouse model of the graft-versus-host reaction.

Cell therapy using MSCs (mesenchymal stem cells) might be effective treatment for refractory GVHD (graft-versus-host disease). However, the fate and distribution of MSCs after transplantation remains unclear. In this study, an animal model was developed to monitor the dynamic distribution of MSCs in mice with GVHD. A GVHD mouse model was established by transplanting C57BL/6 donor bone marrow cells and C57BL/6 EGFP (enhanced green fluorescent protein) splenocytes into lethally irradiated BALB/c nude recipient mice. Donor MSCs were obtained from MHC-identical C57BL/6 RFP (red fluorescent protein) mice and infused into the recipient mice on the same transplantation day. In vivo movement of the donor splenocytes (EGFP) and MSCs (RFP) were evaluated by measuring the biofluorescence (IVIS-Xenogen system). Donor splenocytes and MSCs reached the lungs first, and then the gastrointestinal tract, lymph nodes and skin, in that order; the transit time and localization site of these cells were very similar. In the recipient mouse with GVHD, the number of detectable cells declined with time, as assessed by biofluorescence imaging and confirmed by RT (real-time)-PCR. This bioimaging system might be useful for preclinical testing and the design of therapeutic strategies for monitoring the dynamic distribution of MSCs with GVHD.

Xanthogranulomatous pancreatitis presents as a solid tumor mass: a case report.

Xanthogranulomatous inflammation (XGI) is a rare, idiopathic process in which lipid-laden histiocytes are deposited at various locations in the body. Although XGI has been reported to occur in various organs such as the gallbladder, kidney, bone, stomach, colon, appendix, lymph nodes, urachus, and urinary bladder and in soft tissues, xanthogranulomatous pancreatitis (XGP) is extremely rare. Herein, we report a case of XGP occurring in a 70-yr-old woman, who presented with abdominal pain for several months. On physical examination, mild epigastric tenderness was noted. Abdomen CT scan revealed a low attenuated mass in uncinate process of pancreas, suggesting malignant lesion. Whipple's operation was performed and the final pathologic diagnosis was XGP. The patient's post-operative course was uneventful, and no recurrence was found within 7 months of the operation. When a pancreatic mass does not show clinico-radiological features typical of common pancreatic neoplasms, XGP should be considered for a differential diagnosis.

Preparation and evaluation of functional allopurinol imprinted starch based biomaterials for transdermal drug delivery.

This study focuses on the synthesis of functional allopurinol (ALP) imprinted biomaterials for a transdermal drug delivery using mung bean starch (MBS), polyvinyl alcohol (PVA), sodium benzoate (SB) as a crosslinking agent, and poloxamer (PX) as a thermo-sensitive polymer. Prepared functional biomaterials were characterized and evaluated by SEM, FT-IR analysis, and physical properties. Results of ALP recognition properties indicated that adsorbed amounts (Q) of ALP on functional ALP imprinted biomaterials were 3.8 to 4.9-fold higher than that of non-ALP imprinted biomaterial. Results of ALP release revealed that the ALP release rate for PX added biomaterials was 1.10 (36.5 °C) or 1.30 (45 °C) times faster than that at 25 °C. These results indicate that functional ALP imprinted biomaterials have thermo-sensitive properties due to the addition of PX. Results of ALP release using artificial skin indicated that ALP release was increased at a relatively steady-state rate for 3 h and that the ALP release behavior followed the non-Fickian diffusion mechanism.

Gastric Inverted Polyps-Distinctive Subepithelial Lesions of the Stomach: Clinicopathologic Analysis of 12 Cases With an Emphasis on Neoplastic Potential.

Gastric inverted polyps (GIPs) are rare gastric polyps characterized by a submucosal inverted growth of mucosal components. Because of their rarity, they are not well characterized and are diagnostically challenging. We examined 12 cases of GIPs arising in 8 male and 4 female patients (mean age: 56 y). Most GIPs (11/12, 92%) occurred as a single, rounded subepithelial lesion in the body or fundus (mean size: 14.9 mm). Histologically, GIPs consisted of gastric-type glandular epithelium and smooth muscle component, growing in an endophytic manner; however, they displayed significant morphologic variations. We classified GIPs into 3 subtypes by the following features: communication with the mucosal surface, smooth muscle boundary, and tissue organization. The defining characteristics of type 1 were a mucosal communicating structure at the center and a well-defined smooth muscle boundary, resulting in a characteristic low-magnification morphology of a round vase. Type 2 had an organized glandular proliferation with smooth muscle boundary and no central communicating structure. Type 3 GIPs had no mucosal communicating structure or smooth muscle boundary; its key histologic feature was the lobular organization pattern produced by proliferations of cystic or hyperplastic glands and smooth muscle. All type 1 GIPs exhibited coexisting adenocarcinoma (3 cases) or stromal proliferation (3 cases). Three patients with type 2 GIP had separate adenocarcinoma. None of the type 3 GIPs had accompanying carcinoma. In conclusion, GIPs are a heterogenous group showing different morphology and clinical behavior. Notably, type 1 GIP could be considered a precancerous lesion with the potential to develop adenocarcinoma.

Mesenchymal stromal cells inhibit graft-versus-host disease of mice in a dose-dependent manner.

BACKGROUND AIMS: Graft-versus-host disease (GvHD) remains a major complication after allogeneic hematopoietic cell transplantation (HCT). Recent literature demonstrates a potential benefit of human mesenchymal stromal cells (MSC) for the treatment of refractory GvHD; however, the optimal dose remains uncertain. We set out to develop an animal model that can be used to study the effect of MSC on GvHD. METHODS: A GvHD mouse model was established by transplanting C3H/he donor bone marrow (BM) cells and spleen cells into lethally irradiated BALB/c recipient mice. MSC were obtained from C3H/he mice and the C3H/10T1/2 murine MSC line. RESULTS: The mRNA expression of Foxp3 in regional lymph nodes (LN) localized with T cells was markedly increased by the addition of C3H10T1/2 cells in a real-time polymerase chain reaction (PCR). Using a mixed lymphocyte reaction, we determined the optimal splenocyte proliferation inhibition dose (MSC:splenocyte ratios 1:2 and 1:1). Three different C3H10T1/2 cell doses (low, 0.5 x 10(6), intermediate, 1 x 10(6), and high, 2 x 10(6)) with a consistent splenocyte dose (1 x 10(6)) were evaluated for their therapeutic potential in an in vivo GvHD model. The clinical and histologic GvHD score and Kaplan-Meier survival rate were improved after MSC transplantation, and these results demonstrated a dose-dependent inhibition. CONCLUSIONS: We conclude that MSC inhibit GvHD in a dose-dependent manner in this mouse model and this model can be used to study the effects of MSC on GvHD.

Eradication of Helicobacter pylori increases ghrelin mRNA expression in the gastric mucosa.

It has been suggested that Helicobacter pylori eradication may influence production of some peptides in the stomach, which can affect appetite. This hypothesis is controversial. To verify the hypothesis, we conducted this randomized controlled trial using H. pylori infected subjects without any gastrointestinal symptoms. The treatment group received triple H. pylori eradication therapy for 7 days and the control group received no medication. We measured ghrelin, obestatin and the tumor necrosis factor-alpha (TNF-alpha) mRNA levels in endoscopic biopsy specimens and the changes from baseline to follow-up. The plasma active n-octanoyl ghrelin and obestatin levels were measured in both groups. The ghrelin/obestatin ratios in plasma and gastric mRNA expression were calculated at baseline and follow-up. Ghrelin mRNA expression in the fundic mucosa after H. pylori eradication increased significantly compared to the control group (4.47+/-2.14 vs. 1.79+/-0.96, P=0.009), independent of inflammatory changes. However, obestatin mRNA expression decreased in the antral mucosa (-0.57+/-1.06 vs. 0.41+/-0.72, P=0.028). The treatment group showed a marginal increase (P=0.060) in plasma ghrelin/obestatin ratio. The TNF-alpha mRNA expression also decreased significantly with treatment. This randomized controlled trial demonstrates that H. pylori eradication increases ghrelin mRNA expression, independent of inflammatory cell changes.

Gnathostoma hispidum infection in a Korean man returning from China.

Human Gnathostoma hispidum infection is extremely rare in the world literature and has never been reported in the Republic of Korea. A 74-year-old Korean man who returned from China complained of an erythematous papule on his back and admitted to our hospital. Surgical extraction of the lesion and histopathological examination revealed sections of a nematode larva in the deep dermis. The sectioned larva had 1 nucleus in each intestinal cell and was identified as G. hispidum. The patient recalled having eaten freshwater fish when he lived in China. We designated our patient as an imported G. hispidum case from China.