Smart nanomaterials that integrate theranostic and regenerative properties have emerged as novel solutions in modern biomedicine. These multifunctional platforms combine targeted therapy, advanced imaging, and tissue repair processes into one single scaffold, facilitating real-time monitoring, precise drug administration, and accelerated healing. By utilizing stimulus-responsiveness such as light, pH, or temperature triggers, various nanomaterials (metallic, polymeric, carbon-based, and hybrid) may modify their therapeutic profiles while maintaining the mechanical support necessary for tissue regeneration. Meanwhile, AI-driven approaches progressively aid in rational design and manufacturing scale-up, improving reproducibility and customizing medicines to individual patient situations. Although significant in vivo achievements, long-term safety, regulatory issues, and manufacturing complexity persist as obstacles to clinical translation. This review offers a thorough examination of the approaches by which smart nanomaterials function in diagnosis and treatment, and scaffold-mediated regeneration. We will further examine prospective possibilities for standardized assessments, data methods, and interdisciplinary cooperation. These all-in-one systems have the capacity to transform regenerative medicine and oncology by providing minimally invasive, cost-effective, and patient-centered therapies that integrate diagnostics, therapy, and tissue reconstruction inside a single platform.
Abstract Background and Aims IgA nephropathy is one of the most common chronic glomerulonephritis and 30-45% falls into chronic kidney disease over a period of 20 to 25 years. Lots of treatment regimens are tried such as RAAS blocker, corticosteroids, complement inhibitors, Nefecon, Atrasentan, SGLT2 inhibitor etc., however disappearance of proteinuria has been regarded as surrogate marker of improvement. We performed follow up renal biopsy to confirm the efficacy of disappearance of proteinuria. Method During last 10 years, our clinic performed 1,867 cases of renal biopsies at OPD level. Of which 585 cases (31.3%) were IgA nephropathy. We performed follow up renal biopsies in 149 cases, who showed improved proteinuria after methylprednisolone pulse therapy. Follow renal biopsy findings were divided into 3 groups: One cycle of methylprednisolone pulse therapy consists of methylprednisolone (20-30 mg/kg, max 1 gm/day) for 3 consecutive days. Depends on the pathological grade, we performed 3 to 17 cycles every 2 weeks. Results Male to female ratio was 0.96(73:76), Mean age was 38.4 years old. Of the 149 follow up biopsies, 75 cases (50%) showed improved pathology (Group A), 60 cases (40%) showed no pathological changes (Group B) and 14 cases (10%) showed aggravated pathology (Group C). Conclusion Normalized proteinuria could not be a surrogate marker of renal improvement, because only 50% showed pathological improvement. Follow up renal biopsy might be a mandatory procedure to define the efficacy of treatment in IgA nephropathy.
Aims: Adaptation to oxidative stress is essential for maintaining protein and redox homeostasis in mammalian cells. Palmitic acid (PA) plays a central role in oxidative stress and immunoproteasome regulation in podocytes and diabetes, and eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) have beneficial impact on diabetes. The role of Nrf2 in adaptation to oxidative stress and regulation of immunoproteasome by PA and EPA/DHA in podocytes and diabetic kidneys is not well defined. The present study describes the effect of PA- and EPA/DHA-induced oxidative stress in regulating Nrf2/immuoproteasome pathway in a model system relevant to diabetic nephropathy (DN). Results: Short PA exposure to podocytes promotes the upregulation of antioxidant proteins and immunoproteasome mediated by Nrf2, leading to acute transient oxidative stress adaptation. Both short- and long-term incubation of EPA or DHA in podocytes induced oxidative stress and activation of Nrf2, causing persistent oxidative stress adaptation. Long PA exposure to podocytes decreased the Nrf2 activity, and EPA/DHA attenuated these effects of PA. In db/db mice, feeding of EPA/DHA-rich fish oil increased oxidative stress in kidneys and induced renal cortical Nrf2 nuclear translocation and immunoproteasome overexpression, inhibiting the progression of DN. Innovation and Conclusion: We demonstrate an oxidative stress adaptation mechanism by PA and EPA/DHA regulated by Nrf2 in podocytes and kidneys of type 2 diabetes. This work provides an important insight into the pathogenetic mechanisms of DN by PA-induced oxidative stress. We conclude that activation of Nrf2-immunoproteasome signaling pathway by EPA/DHA plays a crucial role in abrogating the proteotoxic stress in DN. Antioxid. Redox Signal. 42, 751-766.
Anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV) is a complex systemic autoimmune disease characterized by small vessel vasculitis. Typically, the relapse rate is lower in patients with end-stage kidney disease (ESKD) than in those with chronic kidney disease, prior to dialysis. Here, we report a rare case of multi-organ relapse in a patient with myeloperoxidase (MPO)-AAV who underwent hemodialysis following coronavirus disease 2019 (COVID-19). A man in his 70s with type 2 diabetes and hypertension was undergoing maintenance hemodialysis for ESKD resulting from MPO-AAV glomerulonephritis. Following severe acute respiratory syndrome coronavirus 2 infection, the patient was hospitalized for persistent nausea and vomiting. No significant findings were observed, including in endoscopy. However, the patient experienced severe symptoms that hindered oral intake and was refractory to pharmacological therapy. Additionally, despite receiving antibiotics and antituberculosis treatment, the patient experienced persistent unexplained pleural effusion. Moreover, the patient’s level of consciousness rapidly deteriorated during hospitalization. Although C-reactive protein levels and MPO-ANCA titers were elevated, no evidence of infection was detected on brain imaging or cerebrospinal fluid analysis. Therefore, we diagnosed this case as a relapse of AAV and promptly administered methylprednisolone pulse therapy and rituximab. Subsequently, all aforementioned symptoms in the patient improved, and the current ANCA levels remain negative. Thus, the relapse of AAV after COVID-19 is rare; however, it can present in several ways in patients undergoing dialysis. Therefore, clinicians should closely monitor ANCA titers and subtle symptoms, even in patients with dialysis-dependent AAV.
To prevent the spread of the coronavirus disease 2019 (COVID-19) pandemic, vaccines have been authorized for emergency use and implemented worldwide. We present a case of de novo glomerulonephritis (GN) after use of the COVID-19 mRNA vaccine BNT162b2. A 48-year-old man with no relevant medical history was referred for sudden and persistent worsening of renal insufficiency 1.5 months after the second vaccine dose. He had arthralgia and skin rash a week after vaccination. Abdominal pain and diarrhea started 2 weeks later, and he was admitted to the hospital for enteritis treatment. Colonoscopy showed multiple ulcerations and petechiae suggestive of vasculitis in the terminal ileum. After prednisolone therapy, his gastrointestinal symptoms improved, but his renal function continued to deteriorate. Based on kidney biopsy findings and nephrotic-range proteinuria (5,306 mg/24 hours), he was diagnosed with anti-neutrophil cytoplasmic autoantibody (ANCA)-negative pauci-immune crescentic GN (CrGN). He received high-dose steroid pulse therapy and oral cyclophosphamide, and then, gradually underwent steroid tapering, with improvement in proteinuria and renal function over several weeks. Several cases of GN suspected to be related to COVID-19 vaccines have been reported. To our knowledge, this is the first case report of ANCA-negative pauci-immune crescentic CrGN with extrarenal involvement after COVID-19 mRNA vaccination. Our finding expands the spectrum of COVID-19 vaccine-associated GN.
glucose, red blood cells (RBCs), high-power and (WBC) count, 4 per high-power WBC 3 ; hemoglobin, g/dL; platelet count, 3 ; serum total protein, g/dL; albumin, g/dL; total cholesterol,
Abstract BACKGROUND AND AIMS The most common cause of the end-stage renal disease is diabetes and hypertension. However, most centers do not try to find the cause of hypertension in patients with early-stage CKD but give antihypertensive medicine because most centers regard the cause as essential hypertension. Since blood pressure is regulated by the kidneys, we tried to find the cause of hypertension related to kidney disease. METHOD We carried out a single-center retrospective analysis of 1440 kidney biopsies performed for 8 years at a single center in Korea. All cases were done at the OPD level without admission, of which 367 cases (25.5%) showed hypertension/early-stage CKD with normal urinary findings at the time of renal biopsy. RESULTS The results are as follows in order of frequencies: IgA nephropathy (32.7%), mild focal nonspecific glomerulonephritis (GN) (17.7%), focal segmental glomerulosclerosis (FSGS) (15.3%), diffuse mesangial proliferative GN (12.8%), interstitial nephritis with tubular atrophy (7.6%), podocyte disease (3.3%) and membranous nephropathy (1.9%), and others include lupus nephritis, membranoproliferative GN, C1q nephropathy, C3GN, malignant hypertension (1.4%), etc. Most patients (95%) with hypertension/early-stage CKD were associated with chronic glomerulonephritis. Most patients with serious glomerular disease that may progress to ESRD, such as IgAN, FSGS and diffuse mesangial proliferative glomerulonephritis, have improved by aggressive immunotherapy. CONCLUSION In conclusion, before considering antihypertensive medicine in patients with early-stage CKD, a renal biopsy might be a mandatory procedure to save the kidney because more than 90% of cases are associated with glomerular disease.
Trichoderma cornu-damae is a poisonous mushroom that contains trichothecene mycotoxins. The complete mitochondrial genome of this mushroom was determined using next-generation sequencing. This mitogenome is a circular molecule 94,608 bp in length with a GC content of 27.94% and contains 15 protein-coding genes, two rRNA genes (rnl and rns), and 25 tRNA genes. Phylogenetic analysis placed T. cornu-damae in the family Hypocreaceae group, which includes the genus Trichoderma. The mitogenome of T. cornu-damae will contribute to our understanding of the phylogeny, taxonomy, and population genetics of this mushroom.
Gymnopilus junonius, a well-known poisonous mushroom, is distributed worldwide. It contains a hallucinogenic alkaloid psilocybin and several other bioactive compounds. The mitochondrial genome, a circular DNA molecule of 161,145 bp, comprises 15 protein-coding genes, 24 transfer RNA genes, and 2 ribosomal RNA genes. The guanine-cytosine content was 31.56%. Based on the mitochondrial genome sequence, a phylogenetic tree was constructed to demonstrate the phylogenetic relationship. In this study, the phylogenetic positions of G. junonius and its related genera were determined.
Lactifluus (Pers.) Roussel is an ectomycorrhizal genus that was recently recognized to be distinct from the genus Lactarius. To date, 226 Lactifluus species have been reported worldwide. Misidentification of Lactifluus species is common because of intraspecific morphological variation, cryptic diversity, and the limited number of taxonomic keys available. Molecular data are indispensable for species delimitation; a multilocus phylogenetic analysis showed that most Asian Lactifluus species are not conspecific with morphologically similar species present on other continents. In particular, Korea has misused European and North American Lactifluus names. In this study, we evaluated the taxonomy of Lactifluus in Korea using both morphological and multilocus molecular (ITS, nrLSU, rpb1, and rpb2) data. We examined 199 Lactifluus specimens collected between 1980 and 2016, and a total of 24 species across the four Lactifluus subgenera were identified. All Korean species are distinct and clearly separated from European and North American species. Five taxa corresponded to previously described species from Asia and the remaining 19 taxa are confirmed as new species. Herein, we provide keys to the Korean Lactifluus species within their subgenera, molecular phylogenies, a summary of diversity, and detailed description of the new species.
Palmitic acid (PA) leads to lipotoxicity in type 2 diabetes and induces oxidative stress in podocytes. Oxidized cellular proteins are degraded by proteasomes. The role of proteasomes in PA- or oxidative stress-induced podocyte injury and pathogenesis of diabetic nephropathy (DN) is unknown. We investigated the effects of PA on expression of 20S and 26S proteasomes, proteasome activator 28 (PA28) regulators, and the immunoproteasome in cultured podocytes and renal cortical tissues of db/db and db/m mice using Western blot analysis. Glomerular areas and glomerular basement membrane (GBM) widths of db/db and db/m mice were examined using morphometry. Short-term incubation of PA or low levels of H2O2 upregulated only the immunoproteasome in cultured podocytes. Long-term exposure of podocytes to PA ultimately downregulated the immunoproteasome as with other proteasomes, whereas oleic acid (OA) or eicosapentaenoic acid (EPA) restored the PA-induced decreased protein levels. In db/db mice, renal cortical immunoproteasome expression with PA28α was significantly decreased compared with db/m mice, and glomerular areas and GBM widths were significantly increased compared with db/m mice. Feeding of an OA-rich olive oil or EPA-rich fish oil protected db/db mice against the reduced renal cortical immunoproteasome expression, glomerular enlargement, and GBM thickening. These results demonstrate that lipotoxicity downregulates the immunoproteasome in podocytes and kidneys in type 2 diabetes and that OA and EPA protected type 2 diabetic mice against decreased renal cortical immunoproteasome expression and the progression of DN. Given this, lipotoxicity-induced podocyte injury with impaired immunoproteasome expression appears to play an important role in the pathogenesis of DN.NEW & NOTEWORTHY In podocytes, PA rapidly induced immunoproteasome expression but ultimately decreased it, while OA and EPA restored the decreased immunoproteasome levels. In the renal cortex of type 2 diabetic mice, immunoproteasome expression was significantly decreased, whereas feeding of OA-rich olive oil or EPA-rich fish oil diets protected them against the reduced immunoproteasome expression and progression of diabetic nephropathy. Thus, lipotoxicity-induced podocyte injury with impaired immunoproteasome expression may be related to the pathogenesis of diabetic nephropathy.
Abstract Background and Aims Renal biopsy is an essential procedure for diagnosis and prognosis of the glomerular diseases, however needs a lot of skill and experience to do and usually requires admission for a couple of days, unless sometimes needs an embolization, transfusion, nephrectomy etc. We have an experience of more than 3,000 cases of renal biopsy without major complications such as bleeding, embolization, nephrectomy etc.. Recently we performed 309 cases of renal biopsies, whose age is under 20 year old, at the OPD level without admission. Method Before renal biopsy we checked bleeding tendencies and blood thinning agents were hold for more than 1 week. Kidney biopsy was done under local lidocain anesthetic at biopsy site and IV ketamine in uncooperative children. Biopsy needle was inserted under the ultrasound guide(GE LogiQ E9) at the lower pole of the kidney. We checked renal hematoma, AV-fistula formation etc. by ultrasound 3 times every one hour until go home. Biopsy materials were sent to H.S.Lee’s pathology lab. All patients went home in 6 hours after procedure. As far as we know, our clinic is the world’s first time try doing kidney biopsy at OPD plus pathology together, although some kidney pathology reading centers are available in some place. IF results were reported by on-line on the day of kidney biopsy after 5 hours and LM and EM were reported by on-line within two days. All cases went home after 6 hours of procedure. Results We performed 309 cases of renal biopsy at OPD level without any major complications, of which 43 cases were follow up renal biopsies. No major complications were noted such as bleeding, AV fistular, embolization, nephrectomy etc.. Male to female ratio was 1.24. Age distribution was from 2 to 20 year-old. Biopsy results were as follows; mesangial proliferative glomerulonephritis 82 cases(26.51%), IgA nephropathy 81 cases(26.2%), mild focal nonspecific glomerulonephritis 45 cases(14.6%), HSP 23 cases(7.4%), focal segmental glomerulosclerosis 17 cases(5.5%), podocyte disease 13 cases (4.2%), Alport’s syndrome 10 cases(3.2%), minor glomerular change 10 cases (3.2%), MPGN 8 cases (2.6%), membranous nephropathy 6 cases(1.9%), and Lupus nephritis, C1q nephropathy, C3 nephropathy, obesity related nephropathy were 11 cases respectively and others include acute PSGN, chronic tubulointerstitial nephritis. Conclusion OPD level percutaneous renal biopsy in children is no more a dangerous procedure if performed exactly at lower pole of the kidney, with close follow up for 6 hours by ultrasound examination.
Chaga mushrooms are widely used in folk remedies and in alternative medicine. Contrary to many beneficial effects, its adverse effect is rarely reported. We here report a case of end-stage renal disease after long-term taking Chaga mushroom. A 49-year-old Korean man with end stage renal disease (ESRD) was transferred to our hospital. Review of kidney biopsy finding was consistent with chronic tubulointerstitial nephritis with oxalate crystal deposits and drug history revealed long-term exposure to Chaga mushroom powder due to intractable atopic dermatitis. We suspected the association between Chaga mushroom and oxalate nephropathy, and measured the oxalate content of remained Chaga mushroom. The Chaga mushroom had extremely high oxalate content (14.2/100 g). Estimated daily oxalate intake of our case was 2 times for four years and 5 times for one year higher than that of usual diet. Chaga mushroom is a potential risk factor of chronic kidney disease considering high oxalate content. Nephrologist should consider oxalate nephropathy in ESRD patients exposed to Chaga mushrooms.
Macrofungi play important roles in forest ecology as wood decayers, symbionts, and pathogens of living trees. For the effective forest management, it is imperative to have a comprehensive overview of macrofungi diversity in specific areas. As a part of the National Institute of Biological Resources projects for discovering indigenous fungi in Korea, we collected macrofungi in Gayasan National Park from 2017 to 2018. These specimens were identified based on morphological characteristics and sequence analysis of internal transcribed spacer (ITS) or the nuclear large subunit rRNA (LSU) region. We discovered 17 macrofungi new to Korea: Butyrea japonica, Ceriporia nanlingensis, Coltricia weii, Coltriciella subglobosa, Crepidotus crocophyllus, Cylindrobasidium laeve, Fulvoderma scaurum, Laetiporus cremeiporus, Lentinellus castoreus, Leucogyrophana mollusca, Marasmius insolitus, Nidularia deformis, Phaeophlebiopsis peniophoroides, Phanerochaete angustocystidiata, Phlebiopsis pilatii, Postia coeruleivirens, and Tengioboletus fujianensis. We described their detailed morphological characteristics.
Species of Laccaria (Hydnangiaceae, Agaricales, and Basidiomycota) are well-known ectomycorrhizal symbionts of a broad range of hosts. Laccaria species are characterized by brown, orange, or purple colored basidiocarps, and globose or oblong, echinulate and multinucleate basidiospores. While some Laccaria species are easily identified at the species level using only the morphological characteristics, others are hard to distinguish at the species level due to small differences in morphology. Heretofore, ten Laccaria species have been reported in Korea. While studying the fungal diversity in the National Parks of Korea, two new Laccaria species were discovered. Species identification was done based on molecular analyses (ITS, 28S rDNA, rpb2, and tef1), then were confirmed by their corresponding morphologies. The two newly discovered Laccaria species are proposed here as Laccaria macrobasidia and Laccaria griseolilacina. The unique morphological characters of L. macrobasidia that distinguish it from its closely related species are orange-brown colored basidiocarp, long basidia and the absence of cheilocystidia. L. griseolilacina is characterized by a light grayish lavender-colored pileus and the absence of cheilocystidia. Two new species are described and illustrated in the present paper.
Glomerular diseases, a set of debilitating and complex disease entities, are related to mortality and morbidity. To gain insight into pathophysiology and novel treatment targets of glomerular disease, various types of biospecimens linked to deep clinical phenotyping including clinical information, digital pathology, and well-defined outcomes are required. We provide the rationale and design of the KOrea Renal biobank NEtwoRk System TOward Next-generation analysis (KORNERSTONE). The KORNERSTONE, which has been initiated by Korea Centres for Disease Control and Prevention, is designed as a multi-centre, prospective cohort study and biobank for glomerular diseases. Clinical data, questionnaires will be collected at the time of kidney biopsy and subsequently every 1 year after kidney biopsy. All of the clinical data will be extracted from the electrical health record and automatically uploaded to the web-based database. High-quality digital pathologies are obtained and connected in the database. Various types of biospecimens are collected at baseline and during follow-up: serum, urine, buffy coat, stool, glomerular complementary DNA (cDNA), tubulointerstitial cDNA. All data and biospecimens are processed and stored in a standardised manner. The primary outcomes are mortality and end-stage renal disease. The secondary outcomes will be deterioration renal function, remission of proteinuria, cardiovascular events and quality of life. Ethical approval has been obtained from the institutional review board of each participating centre and ethics oversight committee. The KORNERSTONE is designed to deliver pioneer insights into glomerular diseases. The study design allows comprehensive, integrated and high-quality data collection on baseline laboratory findings, clinical outcomes including administrative data and digital pathologic images. This may provide various biospecimens and information to many researchers, establish the rationale for future more individualised treatment strategies for glomerular diseases. NCT03929887.
Russula subsection Amoeninae is morphologically defined by a dry velvety pileus surface, a complete absence of cystidia with heteromorphous contents in all tissues, and spores without amyloid suprahilar spot. Thirty-four species within subsection Amoeninae have been published worldwide. Although most Russula species in South Korea have been assigned European or North American names, recent molecular studies have shown that Russula species from different continents are not conspecific. Therefore, the present study aims to: 1) define which species of Russula subsection Amoeninae occur on each continent using molecular phylogenetic analyses; 2) revise the taxonomy of Korean Amoeninae. The phylogenetic analyses using the internal transcribed spacer (ITS) and multilocus sequences showed that subsection Amoeninae is monophyletic within subgenus Heterophyllidiae section Heterophyllae. A total of 21 Russula subsection Amoeninae species were confirmed from Asia, Australia, Europe, North America, and Central America, and species from different continents formed separate clades. Three species were recognized from South Korea and were clearly separated from the European and North American species. These species are R. bella, also reported from Japan, a new species described herein, Russula orientipurpurea, and a new species undescribed due to insufficient material.