MPO-ANCA-positive rapidly progressive glomerulonephritis after COVID-19 vaccination during treatment of plaque psoriasis with bimekizumab.

A 75-year-old man presented with MPO-ANCA-positive rapidly progressive glomerulonephritis after COVID-19 vaccination during the treatment of plaque psoriasis vulgaris with bimekizumab. Bimekizumab, an anti-IL17 monoclonal antibody, was regularly administered to control the activity of plaque psoriasis. After receiving the sixth COVID-19 vaccine, his kidney function rapidly declined over the course of weeks. Urinalysis showed microscopic hematuria and proteinuria with deformed red blood cells and granular cast. The immunology test was positive for MPO-ANCA. The patient was clinically diagnosed with MPO-ANCA-associated glomerulonephritis. As the patient lost his appetite and developed lower extremity edema with low eGFR (< 15 ml/min/1.73m2) on admission day, hemodialysis induction was initiated along with methylprednisolone pulse, followed by oral prednisolone. The kidney function and urine volume were improved in response to immunosuppressive therapy, and withdrawal from hemodialysis was considered. However, the patient developed a catheter infection due to methicillin-sensitive Staphylococcus aureus 2 weeks after the initial prednisolone treatment, causing a decline in kidney function. Antibiotics treatment for the catheter infection was effective, but kidney function remained low, resulting in dependence on regular hemodialysis. COVID-19 vaccination provides significant improvement in overall prognosis; however, there have been reports of kidney function decline and exacerbation of hematuria in patients with IgA nephropathy following vaccination. The incidence of MPO-ANCA-associated glomerulonephritis after COVID-19 vaccination was rare. Data accumulation is warranted to understand the risk factors for secondary MPO-ANCA glomerulonephritis after COVID-19 vaccination. Regular monitoring of urinalysis and kidney function after COVID-19 vaccination is recommended in patients with psoriasis vulgaris treated with IL17 monoclonal antibodies.

Association between sarcopenia and urinary dysfunction in patients with dysphagia.

INTRODUCTION: The objective was to determine the relationship between sarcopenia and urinary dysfunction in patients with dysphagia. MATERIAL AND METHODS: A cross-sectional study was conducted on 460 Japanese Sarcopenic Dysphagia Database participants. Urinary dysfunction was defined as either urinary incontinence or urethral catheter use. Sarcopenia was diagnosed according to the Asian Working Group for Sarcopenia 2019 criteria. Univariate and multivariate analyses assessed the association between urinary dysfunction and sarcopenia, calf circumference (CC), handgrip strength (HGS), and Barthel Index (BI). Logistic regression analysis was performed for urinary dysfunction adjusted for age, sex, setting, and CCI in addition to BI and HGS or CC or sarcopenia (model 1) or FILS and BI (model 2). RESULTS: The mean age was 80.8 ± 10.5 years and urinary dysfunction in 137 participants. Urinary dysfunction was not associated with sarcopenia (123 versus 281, p = 0.440) but was associated with CC (27.4 ± 4.2 versus 28.5 ± 3.9, p = 0.009), HGS (9.7 ± 7.9 versus 14.4 ± 9.3, p < 0.001), and BI (19.9 ± 0.3 versus 20.3 ± 0.2, p < 0.001). Logistic regression analysis showed urinary dysfunction was associated with HGS (OR: 0.968, CI: 0.938, 0.998) and BI (OR: 0.955, CI: 0.943, 0.966). The cutoff was 19 kg for men (sensitivity 0.786, specificity 0.56, Area Under Curve (AUC) 0.689) and 6.1 kg for women (sensitivity 0.493, specificity 0.774, AUC 0.639) in HGS and 27.5 points in BI (sensitivity 0.781, specificity 0.604, AUC 0.740). CONCLUSION: Sarcopenia was not associated with urinary dysfunction. However, HGS and BI were related to urinary dysfunction.

Temporomandibular joint ankylosis suspected to be associated with ankylosing spondylitis based on cervical computed tomography images: A pictorial essay.

This report showed a case of temporomandibular joint (TMJ) ankylosis suspected to be associated with ankylosing spondylitis based on the observation of bony ankylosis of the cervical spine on computed tomography (CT) images. A 53-year-old man presented with a chief complaint of difficulty in opening his mouth. His medical history indicated that in his 20s, he became aware of the difficulty in moving his neck. CT revealed marked osteoarthritic changes in the right mandibular condyle, suggesting fibrotic TMJ ankylosis. In addition, bony ankylosis of the cervical vertebral body and facet joints from the axis (C2) to C5 in continuity was observed. CT of the entire spine also showed bony deformity of the sacroiliac joints and bony ankylosis. Based on these findings, ankylosing spondylitis was suspected. The possibility of an ankylosing spondylitis complication should be considered in cases of TMJ ankylosis if bony ankylosis of the cervical spine is observed.

Autonomous differentiation of transgenic cells requiring no external hormone application: the endogenous gene expression and phytohormone behaviors.

The ectopic overexpression of developmental regulator (DR) genes has been reported to improve the transformation in recalcitrant plant species because of the promotion of cellular differentiation during cell culture processes. In other words, the external plant growth regulator (PGR) application during the tissue and cell culture process is still required in cases utilizing DR genes for plant regeneration. Here, the effect of Arabidopsis BABY BOOM (BBM) and WUSCHEL (WUS) on the differentiation of tobacco transgenic cells was examined. We found that the SRDX fusion to WUS, when co-expressed with the BBM-VP16 fusion gene, significantly influenced the induction of autonomous differentiation under PGR-free culture conditions, with similar effects in some other plant species. Furthermore, to understand the endogenous background underlying cell differentiation toward regeneration, phytohormone and RNA-seq analyses were performed using tobacco leaf explants in which transgenic cells were autonomously differentiating. The levels of active auxins, cytokinins, abscisic acid, and inactive gibberellins increased as cell differentiation proceeded toward organogenesis. Gene Ontology terms related to phytohormones and organogenesis were identified as differentially expressed genes, in addition to those related to polysaccharide and nitrate metabolism. The qRT-PCR four selected genes as DEGs supported the RNA-seq data. This differentiation induction system and the reported phytohormone and transcript profiles provide a foundation for the development of PGR-free tissue cultures of various plant species, facilitating future biotechnological breeding.

Detecting and exploring kidney-derived extracellular vesicles in plasma.

BACKGROUND: Extracellular vesicles (EVs) have received considerable attention as ideal biomarkers for kidney diseases. Most reports have focused on urinary EVs, that are mainly derived from the cells in the urinary tract. However, the detection and the application of kidney-derived EVs in plasma remains uncertain. METHODS: We examined the kidney-derived small EVs (sEVs) in plasma that were supposedly released from renal mesangial and glomerular endothelial cells, using clinical samples from healthy controls and patients with kidney transplants. Plasma from healthy controls underwent ultracentrifugation, followed by on-bead flow cytometry, targeting α8 integrin, an antigen-specific to mesangial cells. To confirm the presence of kidney-derived sEVs in peripheral blood, plasma from ABO-incompatible kidney transplant recipients was ultracentrifuged, followed by western blotting for donor blood type antigens. RESULTS: Immunohistochemistry and immunoelectron microscopy confirmed α8 integrin expression in kidney mesangial cells and their sEVs. The CD9-α8 integrin double-positive sEVs were successfully detected using on-bead flow cytometry. Western blot analysis further revealed transplanted kidney-derived sEVs containing blood type B antigens in non-blood type B recipients, who had received kidneys from blood type B donors. Notably, a patient experiencing graft kidney loss exhibited diminished signals of sEVs containing donor blood type antigens. CONCLUSION: Our findings demonstrate the potential usefulness of kidney-derived sEVs in plasma in future research for kidney diseases.

The Effect of Cholesterol Content on the Adjuvant Activity of Nucleic-Acid-Free Lipid Nanoparticles.

RNA vaccines are applicable to the treatment of various infectious diseases via the inducement of robust immune responses against target antigens by expressing antigen proteins in the human body. The delivery of messenger RNA by lipid nanoparticles (LNPs) has become a versatile drug delivery system used in the administration of RNA vaccines. LNPs are widely considered to possess adjuvant activity that induces a strong immune response. However, the properties of LNPs that contribute to their adjuvant activity continue to require clarification. To characterize the relationships between the lipid composition, particle morphology, and adjuvant activity of LNPs, the nanostructures of LNPs and their antibody production were evaluated. To simply compare the adjuvant activity of LNPs, empty LNPs were subcutaneously injected with recombinant proteins. Consistent with previous research, the presence of ionizable lipids was one of the determinant factors. Adjuvant activity was induced when a tiny cholesterol assembly (cholesterol-induced phase, ChiP) was formed according to the amount of cholesterol present. Moreover, adjuvant activity was diminished when the content of cholesterol was excessive. Thus, it is plausible that an intermediate structure of cholesterol (not in a crystalline-like state) in an intra-particle space could be closely related to the immunogenicity of LNPs.

Crescentic glomerulonephritis associated with syphilis: a case report and review of the literature.

BACKGROUND: Crescentic glomerulonephritis with syphilis infection is rare, and the mechanism underlying the formation of glomerular capillary wall damage-induced crescent has not been elucidated. CASE PRESENTATION: A 62-year-old Japanese male showed edema, eruption, and rapid deterioration of the renal function after an acute syphilis infection. A renal biopsy showed crescentic glomerulonephritis with C3 deposition in the glomerular capillary wall, and immunostaining for anti-Treponema pallidum antibody was weakly positive in some interstitium and one glomerulus. Electron microscopy revealed the presence of string-shaped structures in the glomerular capillary walls. After treatment with penicillin followed by prednisolone, the renal function and urinary abnormalities, including Treponema pallidum protein, disappeared. CONCLUSIONS: Crescentic glomerulonephritis associated with syphilis showed a string-shaped deposition in the glomerular capillary and urinary Treponema pallidum protein excretion, and was effectively treated with penicillin and prednisolone.

Sarcopenic Dysphagia and Simplified Rehabilitation Nutrition Care Process: An Update.

Sarcopenic dysphagia is characterized by weakness of swallowing-related muscles associated with whole-body sarcopenia. As the number of patients with sarcopenia increases with the aging of the world, the number of patients with sarcopenic dysphagia is also increasing. The prevalence of sarcopenic dysphagia is high in the institutionalized older people and in patients hospitalized for pneumonia with dysphagia in acute care hospitals. Prevention, early detection and intervention of sarcopenic dysphagia with rehabilitation nutrition are essential. The diagnosis of sarcopenic dysphagia is based on skeletal and swallowing muscle strength and muscle mass. A reliable and validated diagnostic algorithm for sarcopenic dysphagia is used. Sarcopenic dysphagia is associated with malnutrition, which leads to mortality and Activities of Daily Living (ADL) decline. The rehabilitation nutrition approach improves swallowing function, nutrition status, and ADL. A combination of aggressive nutrition therapy to improve nutrition status, dysphagia rehabilitation, physical therapy, and other interventions can be effective for sarcopenic dysphagia. The rehabilitation nutrition care process is used to assess and problem solve the patient's pathology, sarcopenia, and nutrition status. The simplified rehabilitation nutrition care process consists of a nutrition cycle and a rehabilitation cycle, each with five steps: assessment, diagnosis, goal setting, intervention, and monitoring. Nutrition professionals and teams implement the nutrition cycle. Rehabilitation professionals and teams implement the rehabilitation cycle. Both cycles should be done simultaneously. The nutrition diagnosis of undernutrition, overnutrition/obesity, sarcopenia, and goal setting of rehabilitation and body weight are implemented collaboratively.

Basigin is released in extracellular vesicles derived from the renal tubular epithelium in response to albuminuria.

AIM: Irrespective of the cause, albumin/proteinuria induces tubulointerstitial damage and accelerates the progression of kidney diseases. Our series of studies demonstrated that proteinuria, an independent prognostic factor for chronic kidney disease (CKD), is correlated with urinary basigin/CD147 (Bsg) levels. We examined the morphology and origin of Bsg in the tubular lumen through the effects of filtered glucose and protein solutes on the tubules. METHODS: Diabetic kidney disease (DKD) patients (N = 50) were treated with spironolactone 25 mg for 4 weeks or by conservative treatment. The associations between urinary Bsg values and clinical indicators were examined. Primary-cultured proximal tubular epithelial cells (PTECs) from human adult kidneys were exposed to high glucose or bovine serum albumin (BSA). RESULTS: In patients with early phase DKD, urinary Bsg levels were closely correlated with proteinuria but not HbA1c. Full-length Bsg on extracellular vesicles (EVs) was investigated primarily in urine collected from DKD patients. EVs obtained from the urine of DKD patients included Bsg and SGLT2 proteins. Notably, spironolactone treatment concomitantly suppressed the release of Bsg-bearing EVs in correlation with decreased albuminuria. Exposure of PTECs to BSA (but not high glucose) enhanced the storage of supernatant Bsg in EVs despite the absence of exposure-specific changes in Bsg transcription. CONCLUSION: Proteinuria induces the release of Bsg-bearing EVs derived from PTECs into the tubular lumen.

Changes in blood pressure and arterial stiffness monitored using the cardio-ankle vascular index during hemodialysis.

During hemodialysis (HD), blood pressure (BP) changes are frequently observed. However, the mechanism of BP changes during HD has not been fully clarified. The cardio-ankle vascular index (CAVI) reflects the arterial stiffness of the arterial tree from the origin of the aorta to the ankle independent from BP during measurement. Additionally, CAVI reflects functional stiffness in addition to structural stiffness. We aimed to clarify the role of CAVI in regulating the BP system during HD. We included 10 patients undergoing 4-hour HD (total 57 HD sessions). Changes in the CAVI and various hemodynamic parameters were evaluated during each session. During HD, BP decreased and CAVI significantly increased (CAVI, median [interquartile range]; 9.1 [8.4-9.8] [0 min] to 9.6 [9.2-10.2] [240 min], p < 0.05). Changes in CAVI from 0 min to 240 min were significantly correlated with water removal rate (WRR) (r = -0.42, p = 0.002). Changes in CAVI at each measurement point were negatively correlated with ΔBP (Δsystolic BPeach MP, r = -0.23, p < 0.0001; Δdiastolic BPeach MP, r = -0.12, p = 0.029). Whereas one patient exhibited a simultaneous decrease in BP and CAVI during the initial 60 min of HD. Arterial stiffness monitored with CAVI generally increased during HD. CAVI elevation is associated with decreased WWR and BP. An increase in CAVI during HD may reflect the contraction of smooth muscle cells and play an important role in BP maintenance. Hence, measuring CAVI during HD may distinguish the cause of BP changes.

Ready-to-Use-Type Lyophilized Lipid Nanoparticle Formulation for the Postencapsulation of Messenger RNA.

Based on the clinical success of an in vitro transcribed mRNA (IVT-mRNA) that is encapsulated in lipid nanoparticles (mRNA-LNPs), there is a growing demand by researchers to test whether their own biological findings might be applicable for use in mRNA-based therapeutics. However, the equipment and/or know-how required for manufacturing such nanoparticles is often inaccessible. To encourage more innovation in mRNA therapeutics, a simple method for preparing mRNA-LNPs is prerequisite. In this study, we report on a method for encapsulating IVT-mRNA into LNPs by rehydrating a Ready-to-Use empty freeze-dried LNP (LNPs(RtoU)) formulation with IVT-mRNA solution followed by heating. The resulting mRNA-LNPs(RtoU) had a similar intraparticle structure compared to the mRNA-LNPs prepared by conventional microfluidic mixing. In vivo genome editing, a promising application of these types of mRNA-LNPs, was accomplished using the LNPs(RtoU) containing co-encapsulated Cas9-mRNA and a small guide RNA.

Necl2/3-mediated mechanism for tripartite synapse formation.

Ramified, polarized protoplasmic astrocytes interact with synapses via perisynaptic astrocyte processes (PAPs) to form tripartite synapses. These astrocyte-synapse interactions mutually regulate their structures and functions. However, molecular mechanisms for tripartite synapse formation remain elusive. We developed an in vitro co-culture system for mouse astrocytes and neurons that induced astrocyte ramifications and PAP formation. Co-cultured neurons were required for astrocyte ramifications in a neuronal activity-dependent manner, and synaptically-released glutamate and activation of astrocytic mGluR5 metabotropic glutamate receptor were likely involved in astrocyte ramifications. Astrocytic Necl2 trans-interacted with axonal Necl3, inducing astrocyte-synapse interactions and astrocyte functional polarization by recruiting EAAT1/2 glutamate transporters and Kir4.1 K+ channel to the PAPs, without affecting astrocyte ramifications. This Necl2/3 trans-interaction increased functional synapse number. Thus, astrocytic Necl2, synaptically-released glutamate and axonal Necl3 cooperatively formed tripartite glutamatergic synapses in vitro. Studies on hippocampal mossy fiber synapses in Necl3 knockout and Necl2/3 double knockout mice confirmed these previously unreported mechanisms for astrocyte-synapse interactions and astrocyte functional polarization in vivo.

Climate change and nephrology.

Climate change should be of special concern for the nephrologist, as the kidney has a critical role in protecting the host from dehydration, but it is also a favorite target of heat stress and dehydration. Here we discuss how rising temperatures and extreme heat events may affect the kidney. The most severe presentation of heat stress is heat stroke, which can result in severe electrolyte disturbance and both acute and chronic kidney disease (CKD). However, lesser levels of heat stress also have multiple effects, including exacerbating kidney disease and precipitating cardiovascular events in subjects with established kidney disease. Heat stress can also increase the risk for kidney stones, cause multiple electrolyte abnormalities and induce both acute and chronic kidney disease. Recently there have been multiple epidemics of CKD of uncertain etiology in various regions of the world, including Mesoamerica, Sri Lanka, India and Thailand. There is increasing evidence that climate change and heat stress may play a contributory role in these conditions, although other causes, including toxins, could also be involved. As climate change worsens, the nephrologist should prepare for an increase in diseases associated with heat stress and dehydration.

Development of an inducible excision system of a visual marker Ipomoea batatas Myb gene from the genome of transgenic cells.

In the plant genetic transformation process, single selection by a chemical-resistant marker gene occasionally allows the proliferation of non-transgenic cells, escaping selection pressure. The additional use of a visual marker gene is effective for accurate selection. For instance, R2R3-MYB genes are used for regulating anthocyanin biosynthesis; however, constitutive Myb expression in transgenic plants is not always desirable and may cause developmental abnormalities due to excess anthocyanin accumulation. To overcome the remaining problems in the use of Myb as a visible marker, we developed T-DNA. Ipomoea batatas Myb (IbMyb) and Cre expression cassettes were inserted between two loxP sequences, and the hygromycin phosphotransferase (HPT) and green fluorescent protein (GFP) expression cassettes were located outside of the loxP-IbMyb-Cre-loxP region. In the developed system, IbMyb and Cre were excised from the genomes of transgenic cells using heat-inducible Cre-loxP recombination. Upon heat treatment in a general incubator, green shoots emerged from purple tobacco transgenic calli that were pigmented with IbMyb expression. The excision of IbMyb from the genome of green shoots was confirmed using polymerase chain reaction (PCR) and sequencing. GFP expression was observed in the roots of the obtained green transgenic plants. We report that the system developed here operated successfully in tobacco, showing the potential to provide an easier and cheaper visual selection of transgenic cells in the genetic transformation process.

Evaluation of a quantitative PCR-based method for chimerism analysis of Japanese donor/recipient pairs.

Chimerism analysis is a surrogate indicator of graft rejection or relapse after allogeneic hematopoietic stem cell transplantation (HSCT). Although short tandem repeat PCR (STR-PCR) is the usual method, limited sensitivity and technical variability are matters of concern. Quantitative PCR-based methods to detect single nucleotide polymorphisms (SNP-qPCR) are more sensitive, but their informativity and quantitative accuracy are highly variable. For accurate and sensitive chimerism analysis, a set of KMR kits (GenDx, Utrecht, Netherlands), based on detection of insertions/deletions (indels) by qPCR, have been developed. Here, we investigated informativity and validated the accuracy of KMR kits in Japanese donor/recipient pairs and virtual samples of DNA mixtures representative of Japanese genetic diversity. We found that at least one recipient-specific marker among 39 KMR-kit markers was informative in all of 65 Japanese donor/recipient pairs. Moreover, the percentage of recipient chimerism estimated by KMRtrack correlated well with ratios of mixed DNA in virtual samples and with the percentage of chimerism in HSCT recipients estimated by STR-PCR/in-house SNP-qPCR. Moreover, KMRtrack showed better sensitivity with high specificity when compared to STR-PCR to detect recipient chimerism. Chimerism analysis with KMR kits can be a standardized, sensitive, and highly informative method to evaluate the graft status of HSCT recipients.

Naphthalene Diimides Carrying Two ß-Cyclodextrins Prefer Telomere RNA G-Quadruplex Recognition.

Newly synthesized naphthalene diimide carrying two ß-cyclodextrins (NDI-ß-CyDs) showed improved specificity for the parallel G-quadruplex structure alongside the hybrid G-quadruplex structure. Specifically, the highest binding affinity of NDI-ß-CyDs for the telomere RNA G-quadruplex was observed. The binding simulation indicated that ß-cyclodextrins might be available for loop nucleobase inclusion under its complex.

Myricetin improves cognitive function in SAMP8 mice and upregulates brain-derived neurotrophic factor and nerve growth factor.

INTRODUCTION: Considering that neurodegeneration is an irreversible process, an efficient, low-burden approach to prevent dementia is strongly needed. Here, we show that the daily intake of myricetin normalised cognitive dysfunction in senescence-accelerated mouse prone 8 (SAMP8) mice. METHODS: SAMP8 mice were fed a diet supplemented with myricetin and novel object recognition tests and Y-maze tests were performed. Brain-derived neurotrophic factor (BDNF) and nerve growth factor (NGF) in brains of SAMP8 mice were measured. The phosphorylation level of cAMP-response-element-binding protein (CREB) level in brains of SAMP8 mice were evaluated. Also, SH-SY5Y cells were treated with myricetin and cAMP levels were measured. RESULTS: In SAMP8 mice, neurotrophins, including BDNF and NGF, were downregulated relative to levels in their normal counterparts. In addition, myricetin intake upregulated the phosphorylation of CREB, the major transcription factor for BDNF and NGF. Also, myricetin induced cAMP upregulation, and CREB phosphorylation via a cAMP-dependent protein kinase-dependent manner in SH-SY5Y cells. CONCLUSION: Taken together, myricetin improves cognitive function in SAMP8 mice and upregulates BDNF and NGF.

Effectiveness of an actuator-driven pulsed water jet for removal of softened carious dentin.

The aim of this study was to assess the utility of an actuator-driven pulsed water jet (ADPJ) as a hardness-dependent carious dentin removal device by using different outputs. Thirty-six plane surface dental caries samples were treated with the ADPJ at 150, 200, and 250 voltage (12 teeth each). The Knoop hardness number (KHN) and Ca/P mass ratio were measured at 70 µm from the deepest point of the removing groove. Furthermore, three other teeth samples were manually treated with the ADPJ at the three above mentioned voltages (one tooth each) for 1 min. The KHN and Ca/P mass ratio were measured at 70 µm from the surface of the residual dentin part. In both the KHN and Ca/P mass ratio, higher residual dentin depended on the applied voltage of ADPJ. The ADPJ enabled the removal of softened carious dentin in an applied voltage-dependent manner.

Basigin deficiency prevents anaplerosis and ameliorates insulin resistance and hepatosteatosis.

Monocarboxylates, such as lactate and pyruvate, are precursors for biosynthetic pathways, including those for glucose, lipids, and amino acids via the tricarboxylic acid (TCA) cycle and adjacent metabolic networks. The transportation of monocarboxylates across the cellular membrane is performed primarily by monocarboxylate transporters (MCTs), the membrane localization and stabilization of which are facilitated by the transmembrane protein basigin (BSG). Here, we demonstrate that the MCT/BSG axis sits at a crucial intersection of cellular metabolism. Abolishment of MCT1 in the plasma membrane was achieved by Bsg depletion, which led to gluconeogenesis impairment via preventing the influx of lactate and pyruvate into the cell, consequently suppressing the TCA cycle. This net anaplerosis suppression was compensated in part by the increased utilization of glycogenic amino acids (e.g., alanine and glutamine) into the TCA cycle and by activated ketogenesis through fatty acid ß-oxidation. Complementary to these observations, hyperglycemia and hepatic steatosis induced by a high-fat diet were ameliorated in Bsg-deficient mice. Furthermore, Bsg deficiency significantly improved insulin resistance induced by a high-fat diet. Taken together, the plasma membrane-selective modulation of lactate and pyruvate transport through BSG inhibition could potentiate metabolic flexibility to treat metabolic diseases.