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1.
Planta ; 259(6): 149, 2024 May 10.
Artículo en Inglés | MEDLINE | ID: mdl-38724681

RESUMEN

MAIN CONCLUSION: The rice SnRK2 members SAPK4, SAPK5, SAPK7 and SAPK10 are positive regulators involved in the regulation of rice flowering, while other single mutants exhibited no effect on rice flowering. The rice SnRK2 family, comprising 10 members known as SAPK (SnRK2-Associated Protein Kinase), is pivotal in the abscisic acid (ABA) pathway and crucial for various biological processes, such as drought resistance and salt tolerance. Additionally, these members have been implicated in the regulation of rice heading date, a key trait influencing planting area and yield. In this study, we utilized gene editing technology to create mutants in the Songjing 2 (SJ2) background, enabling a comprehensive analyze the role of each SAPK member in rice flowering. We found that SAPK1, SAPK2, and SAPK3 may not directly participate in the regulatory network of rice heading date, while SAPK4, SAPK5, and SAPK7 play positive roles in rice flowering regulation. Notably, polygene deletion resulted in an additive effect on delaying flowering. Our findings corroborate the previous studies indicating the positive regulatory role of SAPK10 in rice flowering, as evidenced by delayed flowering observed in sapk9/10 double mutants. Moving forward, our future research will focus on analyzing the molecular mechanisms underlying SAPKs involvement in rice flowering regulation, aiming to enhance our understanding of the rice heading date relationship network and lay a theoretical foundation for breeding efforts to alter rice ripening dates.


Asunto(s)
Flores , Regulación de la Expresión Génica de las Plantas , Oryza , Proteínas de Plantas , Oryza/genética , Oryza/crecimiento & desarrollo , Oryza/fisiología , Oryza/enzimología , Flores/genética , Flores/crecimiento & desarrollo , Flores/fisiología , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo , Mutación , Edición Génica , Estrés Fisiológico/genética , Proteínas Quinasas/genética , Proteínas Quinasas/metabolismo , Ácido Abscísico/metabolismo , Proteínas Serina-Treonina Quinasas/genética , Proteínas Serina-Treonina Quinasas/metabolismo
2.
Mol Breed ; 44(5): 35, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38736650

RESUMEN

Rice flowering time determines its geographical distribution and yield traits. As a short-day plant, rice can grow in the northern long-day conditions due to the functional mutations of many photosensitive genes. In this study, to identify novel genes or alleles that regulate flowering time in high latitude region, two cultivar, Dongnong 413 (DN413) and Yukimochi (XN) showing extreme early flowering were used for investigation. DN413 is around 4.0 days earlier than XN, and both cultivars can be grown in II (2500 â„ƒ-2700 â„ƒ) to III (2300 â„ƒ-2500 â„ƒ) accumulated temperature zones. We found that the two cultivars shared the same genotype of heading date genes, including Hd1/2/4/5/6/16/17/18, Ehd2, DTH2, SE5, Hd3a. Importantly, a novel Ehd3 allele characterized by a A1146C substitution was identified, which results in the E382D substitution, hereafter the 382 position E is defined as Hap_E and the 382 position D is defined as Hap_D. Association analysis showed that Hap_E is earlier flowering than Hap_D. Subsequently, we construct DN413 Hap_D line by three times back-crossing DN413 with XN, and found the heading date of DN413 Hap_D was 1.7-3.5 days later than DN413. Moreover, Hap_E and Hap_D of Ehd3 were transformed into ehd3 mutant, respectively, and the Ehd3pro:Ehd3D/ehd3 flowered later than that Ehd3pro:Ehd3E/ehd3 by around 4.3 days. Furthermore, we showed Ehd3 functions as a transcriptional suppressor and the substitution of Asp-382 lost the inhibition activity in protoplasts. Finally, a CAPS marker was developed and used for genotyping and marker assistant breeding. Collectively, we discovered a novel functional allele of Ehd3, which can used as a valuable breeding target. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-024-01472-x.

3.
J Org Chem ; 89(7): 5181-5188, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38517737

RESUMEN

This innovative reaction involved the [3+3] annulation of 2-amino-4H-chromen-4-ones and 4-benzylideneoxazol-5(4H)-ones. The process provided quick and easy access to a broad range of structurally diverse and highly functionalized 1,3,4,5-tetrahydro-2H-chromeno[2,3-b]pyridines in moderate to good yields, which possess trans-form C3 and C4 substituents.

4.
Arthritis Res Ther ; 26(1): 76, 2024 Mar 21.
Artículo en Inglés | MEDLINE | ID: mdl-38515127

RESUMEN

BACKGROUND: Autoimmune responses have been suggested to involvement in patients with Behcet's syndrome (BS). There has been growing attention towards the roles of cutaneous lymphocyte antigen (CLA)+ regular T cells (Tregs) in autoimmune diseases. The role of CLA+ Tregs in BS is still uncertain. This study aims to clarify the impact of CLA+ Tregs on BS. METHODS: We collected peripheral blood from a total of 107 patients with BS and 114 healthy controls (HCs). The number of CLA+ Tregs, natural killer (NK) cells, B cells, and several subtypes of CD4+ T cells were detected using flow cytometry and compared between patients and HCs. RESULTS: The absolute number and proportion of CLA+ Tregs among CD4+ T lymphocytes and CD4+ Tregs were lower in patients with BS than in HCs. CLA+ Tregs were positively related with NK cells (r = 0.500, P < 0.001) and B cells (r = 0.470, P < 0.001) and negatively related with effector T cells (r=-0.402, P < 0.001) in patients with BS. Patients with BS and arterial aneurysms had CLA+ Treg cell deficiency. A decreased proportion of CLA+ Tregs was associated with arterial aneurysms in patients with BS. The proportion of CLA+ Tregs in patients with BS increased with corticosteroids and immunosuppressants. CONCLUSION: CLA+ Tregs decrease in association with arterial aneurysm in patients with BS. CLA+ Tregs may be a predictor of response to BS treatment.


Asunto(s)
Aneurisma , Síndrome de Behçet , Antígeno Sialil Lewis X/análogos & derivados , Humanos , Relevancia Clínica , Oligosacáridos , Linfocitos T Reguladores
5.
Kidney Int Rep ; 9(2): 401-409, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38344711

RESUMEN

Introduction: Membranous nephropathy (MN) is the most common cause of proteinuria in syphilis, and neuron-derived neurotrophic factor (NDNF) was recently demonstrated to be the target antigen in syphilis-associated MN. However, the prevalence and clinicopathological characteristics of both NDNF-positive and NDNF-negative MN in Chinese individuals with syphilis infection still remain unknown. Methods: A retrospective study was conducted in 17 patients with MN with history of syphilis infection. The intensity and distribution of NDNF staining, as well as phospholipase A2 receptor (PLA2R) and neural epidermal growth factor-like 1 protein (NELL-1) staining in renal biopsies were assessed. Results: Among the 11 patients with MN with active syphilis infection, positive NDNF staining was shown in 5 patients (46%). The remaining 6 patients demonstrated negative NDNF staining. Of these, 5 patients were PLA2R-positive and 1 patient was PLA2R-negative and NELL-1-negative. Antibiotics were also effective in 3 NDNF-negative patients, suggesting the possibility of syphilis-associated MN. Therefore, the histological positivity rate of NDNF was 63% (5/8 patients) in syphilis-associated MN. In addition, positive NDNF antibody was first confirmed in the serum of 1 patient with NDNF-associated MN. NDNF staining was negative in all 6 patients with MN with previous syphilis infection. Conclusion: Nearly half of the patients with active syphilis infection and MN were NDNF-positive in our study. Positive NDNF staining favors syphilis-associated MN. Circulating anti-NDNF antibody can be detected in the patient's serum sample. In addition, PLA2R or other unknown antigenic protein may also be the target antigens for syphilis-associated MN in Chinese population.

6.
Cell Biochem Funct ; 42(2): e3943, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38379015

RESUMEN

Dapagliflozin (DAPA) are clinically effective in improving diabetic nephropathy (DN). However, whether and how chromatin accessibility changed by DN responds to DAPA treatment is unclear. Therefore, we performed ATAC-seq, RNA-seq, and weighted gene correlation network analysis to identify the chromatin accessibility, the messenger RNA (mRNA) expression, and the correlation between clinical phenotypes and mRNA expression using kidney from three mouse groups: db/m mice (Controls), db/db mice (case group), and those treated with DAPA (treatment group). RNA-Seq and ATAC-seq conjoint analysis revealed many overlapping pathways and networks suggesting that the transcriptional changes of DN and DAPA intervention largely occured dependently on chromatin remodeling. Specifically, the results showed that some key signal transduction pathways, such as immune dysfunction, glucolipid metabolism, oxidative stress and xenobiotic and endobiotic metabolism, were repeatedly enriched in the analysis of the RNA-seq data alone, as well as combined analysis with ATAC-seq data. Furthermore, we identified some candidate genes (UDP glucuronosyltransferase 1 family, Dock2, Tbc1d10c, etc.) and transcriptional regulators (KLF6 and GFI1) that might be associated with DN and DAPA restoration. These reversed genes and regulators confirmed that pathways related to immune response and metabolism pathways were critically involved in DN progression.


Asunto(s)
Compuestos de Bencidrilo , Diabetes Mellitus , Nefropatías Diabéticas , Glucósidos , Ratones , Animales , Nefropatías Diabéticas/tratamiento farmacológico , Nefropatías Diabéticas/genética , Nefropatías Diabéticas/metabolismo , Secuenciación de Inmunoprecipitación de Cromatina , RNA-Seq , Cromatina , ARN Mensajero/metabolismo
7.
Stem Cell Res ; 76: 103357, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38412658

RESUMEN

INF2 mutations cause Charcot-Marie-Tooth disease (CMT), and /or focal segmental glomerulosclerosis (FSGS) in an autosomal dominant inheritance mode, whose underlying mechanism remainsunclear. Here, we report the generation of an iPSC line from a female patient with CMT and FSGS. The iPSC line from the patient's PBMCscarried aheterozygous INF2 deletion mutation (c.315_323delGCGCGCCGT) within the conserved E2. This line exhibited a normal karyotype, high expression of pluripotency markers, and trilineage differentiation potential. This line can be used to dissect the complex pathomechanism through further induction of differentiation into related cells and as a drug screening tool for INF2-associated diseases.


Asunto(s)
Enfermedad de Charcot-Marie-Tooth , Glomeruloesclerosis Focal y Segmentaria , Células Madre Pluripotentes Inducidas , Humanos , Femenino , Glomeruloesclerosis Focal y Segmentaria/genética , Enfermedad de Charcot-Marie-Tooth/genética , Proteínas de Microfilamentos/genética , Proteínas de Microfilamentos/metabolismo , Forminas/genética , Células Madre Pluripotentes Inducidas/metabolismo , Mutación
8.
Kidney Med ; 6(2): 100771, 2024 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-38313808
9.
J Biomater Sci Polym Ed ; 35(4): 501-518, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38198288

RESUMEN

Polyphenolic compound-modified hydrogel wound dressings with excellent wet tissue adhesion, antimicrobial properties, stretchability, and full-thickness skin healing properties are still extremely rare so far. Polyphenolic compounds such as tannic acid or dopamine can improve the antibacterial and bioadhesive properties of hydrogels, and are also polymerization inhibitors for free radical polymerization. In this study, polyacrylic acid (PAA) aqueous solution was first synthesized, and then antibacterial PAA-TA hydrogel was prepared by mixing it with tannic acid (TA) and the crosslinker 1,6-hexanediol bis(2-methyl-1-propionic acid azide) (HBMAP). This method avoids the hindrance of the phenolic hydroxyl groups in TA on acrylic acid polymerization, and we were able to obtain a series of TA hydrogels (in the range of 0-15 wt.%. We applied these PAA-TA hydrogels to wound dressings and found that they had excellent adhesion to biological tissues, and the tensile strength and elongation at break of PAA-TA hydrogels with 15 wt.%TA content were as high as 1.72 MPa and 1446.3% in tensile strength evaluation. In addition, microbiological analysis showed that wound dressings had significant antimicrobial activity against Staphylococcus aureus and Escherichia coli. In vitro wound healing experiments confirmed that the wound dressing was biocompatible and could significantly promote the healing of full-thickness skin defects in the guinea pig model. Our work describes an injectable, self-healing, antimicrobial hydrogel that may have promising clinical applications as a wound dressing material.


Asunto(s)
Resinas Acrílicas , Antiinfecciosos , Hidrogeles , Polifenoles , Animales , Cobayas , Antibacterianos/farmacología , Vendajes , Escherichia coli
10.
Environ Toxicol ; 39(3): 1283-1293, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-37948135

RESUMEN

BACKGROUND: Nonsmall-cell lung cancer (NSCLC) has emerged as one of the dreadful lung cancers globally due to its increased mortality rates. Concerning chemotherapy, gefitinib has been employed as an effective first-line treatment drug for NSCLC. Nonetheless, the acquired resistance to gefitinib has remained one of the treatment obstacles of NSCLC, requiring improvement in the therapeutic effect of gefitinib. METHODS: Initially, reverse transcription-quantitative polymerase chain reaction (RT-qPCR), and Western blotting (WB) analyses were conducted to measure micro-ribose nucleic acid (miRNA, specifically miR-578) and suppressor of cytokine signaling 2 (SOCS2) levels in the clinical samples. Further, NSCLC cell lines resistance to gefitinib, established in vitro, were transfected by miR-578 inhibitor, miR-578 mimic, and si-SOCS2. Similarly, the xenograft mouse model in vivo was constructed to validate the reversing effect of miR-578. RESULTS: Our findings indicated the increased miR-578 expression levels in the gefitinib resistance group. Further, inhibiting the miR-578 expression substantially reversed the gefitinib resistance. In addition, the miR-578 effect was modulated via the SOCS2 expression level. The decreased gefitinib resistance effect of miR-578 was weakened by inhibiting the SOCS2 expression. CONCLUSION: These findings demonstrated that miR-578 effectively abolished gefitinib resistance by regulating the SOCS2 expression within NSCLC cells in vitro and in vivo. Together, these results will undoubtedly support a reference to provide potential molecular therapeutic targets and clinical treatments for treating NSCLC patients.


Asunto(s)
Antineoplásicos , Carcinoma de Pulmón de Células no Pequeñas , Neoplasias Pulmonares , MicroARNs , Humanos , Animales , Ratones , Gefitinib/farmacología , Gefitinib/uso terapéutico , Resistencia a Antineoplásicos , Línea Celular Tumoral , Carcinoma de Pulmón de Células no Pequeñas/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Antineoplásicos/farmacología , Proliferación Celular , Proteínas Supresoras de la Señalización de Citocinas
11.
Brain Res Bull ; 206: 110863, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-38145759

RESUMEN

Chronic pain can induce not only nociceptive but also depressive emotions. A previous study demonstrated that betaine, a commonly used nutrient supplement, has an anti-nociceptive effect, but whether betaine can alleviate chronic pain-induced depressive emotion is elusive. Our current study found that betaine administration significantly eliminated complete Freund's adjuvant (CFA)-induced pain-related depressive-like behaviour. Mechanistically, betaine treatment inhibited microglia and astrocyte activation. Furthermore, betaine significantly promoted the transition of microglia from the M1 to the M2 phenotype, as well as the transition of astrocytes from the A1 to the A2 phenotype. Additionally, the release of pro-inflammatory factors such as IL-18, IL-1ß and IL-6 and anti-inflammatory factors such as IL-10 in the hippocampus induced by CFA were also reversed by betaine administration. Overall, betaine has therapeutic effects on pain-related depressive-like phenotypes caused by CFA, possibly through altering the polarization of microglia and astrocytes to reduce neuroinflammation.


Asunto(s)
Dolor Crónico , Microglía , Ratones , Animales , Betaína/efectos adversos , Astrocitos , Adyuvante de Freund/toxicidad , Inflamación/genética
12.
Stem Cell Res ; 74: 103286, 2024 02.
Artículo en Inglés | MEDLINE | ID: mdl-38141357

RESUMEN

Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disease. Affected patients experience gradual loss of their spinal cord and cortical motor neurons with consequent muscle weakness and emaciation, and eventual respiratory failure. The pathogenesis of ALS remains largely unknown although the FUS (sarcoma fusion gene) gene is known to be one of the major pathogenic genes. We have generated an induced pluripotent stem cell line SMUSHi002-A from an ALS patient who carries a heterozygous mutation c.1562G > A in FUS. This cell line will serve as a useful model to investigate disease pathogenesis and develop potential therapeutic approaches for ALS.


Asunto(s)
Esclerosis Amiotrófica Lateral , Células Madre Pluripotentes Inducidas , Enfermedades Neurodegenerativas , Humanos , Esclerosis Amiotrófica Lateral/patología , Células Madre Pluripotentes Inducidas/metabolismo , Enfermedades Neurodegenerativas/metabolismo , Neuronas Motoras/metabolismo , Mutación/genética , Proteína FUS de Unión a ARN/genética
13.
Arthritis Res Ther ; 25(1): 239, 2023 12 07.
Artículo en Inglés | MEDLINE | ID: mdl-38062524

RESUMEN

BACKGROUND: To classify the different clinical phenotypes and compare the distinct prognoses of microscopic polyangiitis (MPA). METHODS: A retrospective analysis of 436 patients with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitides (AAV) from 2015 to 2022 was conducted in our center, of which 90 patients were diagnosed with MPA and underwent renal biopsy. RESULTS: Among the 90 MPA patients, 63% were female, and the median age at onset was 63 years (25th-75th percentile: 58-68). The median follow-up time was 26 months (25th-75th percentile: 10-53). We identified four subtypes: renal impairment type (cluster 1, 39%), pure type (cluster 2, 22%), systemic inflammation type (cluster 3, 26%), and rapid progress type (cluster 4, 13%). Cluster 1, characterized by renal dysfunction at onset (80%), demonstrated poor prognoses with only 26% achieved complete remission (CR), 11% dying, and 19% developing renal failure. In contrast, patients in cluster 2, exclusively female, most had only kidney involvement showed the best prognoses with 55% achieving CR and none experiencing death or renal failure within 10 years. Cluster 3 mostly consisted of males; high fever and C-reactive protein levels were the primary characteristics. These cases exhibited moderate prognoses with 53% achieving CR, 9% dying, and 4% developing renal failure. Finally, patients in cluster 4, which was characterized by rapidly progressive glomerulonephritis, had the worst prognoses, with none achieving CR, 8% dying, and 75% developing renal failure despite aggressive treatment. CONCLUSIONS: MPA is classified into four subtypes with distinct clinical manifestations and prognoses.


Asunto(s)
Vasculitis Asociada a Anticuerpos Citoplasmáticos Antineutrófilos , Granulomatosis con Poliangitis , Poliangitis Microscópica , Insuficiencia Renal , Masculino , Humanos , Femenino , Persona de Mediana Edad , Poliangitis Microscópica/diagnóstico , Estudios Retrospectivos , Pronóstico , Anticuerpos Anticitoplasma de Neutrófilos , Riñón/patología , Fenotipo , Insuficiencia Renal/patología , Biopsia
14.
Theor Appl Genet ; 137(1): 10, 2023 Dec 16.
Artículo en Inglés | MEDLINE | ID: mdl-38103049

RESUMEN

Rice is a chilling-sensitive plant, and extremely low temperatures seriously decrease rice production. Several genes involved in chilling stress have been reported in rice; however, the chilling signaling in rice remains largely unknown. Here, we investigated the chilling tolerance phenotype of overexpression of constitutive active OsMAPK6 (CAMAPK6-OE) and OsMAPK6 mutant dsg1, and demonstrated that OsMAPK6 positively regulated rice chilling tolerance. It was shown that, under cold stress, the survival rate of dsg1 was significantly lower than that of WT, whereas CAMAPK6-OE display higher survival rate than WT. Physiological assays indicate that ion leakage and dead cell in dsg1 was much more severe than those in WT and CAMAPK6-OE. Consistently, expression of chilling responsive genes in dsg1, including OsCBFs and OsTPP1, was significantly lower than that of in WT and CAMAPK6-OE. Biochemical analyses revealed that chilling stress promotes phosphorylation of OsMAPK6. Besides, we found that OsMAPK6 interacts with and phosphorylates two key regulators in rice cold signaling, OsIPA1 and OsICE1, and then enhance their protein stability. Overall, our results revealed a cold-induced OsMAPK6-OsICE1/OsIPA1 signaling cascade by which OsMAPK6 was involved in rice chilling tolerance, which provides novel insights to understand rice cold response at seedling stage.


Asunto(s)
Oryza , Plantones , Plantones/genética , Plantones/metabolismo , Oryza/metabolismo , Respuesta al Choque por Frío/genética , Frío , Fosforilación , Regulación de la Expresión Génica de las Plantas , Proteínas de Plantas/genética , Proteínas de Plantas/metabolismo
15.
J Org Chem ; 88(20): 14767-14774, 2023 Oct 20.
Artículo en Inglés | MEDLINE | ID: mdl-37820027

RESUMEN

A three-component reaction of 2-amino-4H-chromen-4-ones, aromatic aldehydes, and 4,4-dialkoxycyclohexa-2,5-dien-1-ones for the concise synthesis of chromeno[2,3-c]dihydroisoquinoline derivatives has been investigated. This reaction involved consecutive ZnCl2-promoted Micheal addition and intramolecular Friedel-Crafts alkylation. This synthetic protocol offered several advantages, including the readily accessible starting materials, good functional group tolerance, and simplicity of operation. Additionally, the structures of products obtained were determined based on X-ray diffraction studies.

16.
BMC Nephrol ; 24(1): 242, 2023 08 18.
Artículo en Inglés | MEDLINE | ID: mdl-37596523

RESUMEN

BACKGROUND: Extraglomerular immune complex deposition is rare and only a few membranous nephropathy cases with tubular basement membrane deposits have been reported following allogeneic hematopoietic stem cell transplantation. CASE PRESENTATION: We reported a 56-year-old man with increased serum creatinine after allogeneic hematopoietic stem cell transplantation who underwent a renal biopsy. Tubular interstitial nephritis was identified on light microscope. The unique histologic features were diffuse tubular basement membrane immune complex deposition detected by both immunofluorescence and electron microscopy, while the glomerular involvement was inconspicuous. The differential diagnosis from other forms of tubular basement membrane deposition is discussed. CONCLUSION: Diffuse granular tubular basement membrane immune complex deposition with minimal glomerular involvement is also a manifestation of renal complication in hematopoietic stem cell transplantation recipient. However, the exact mechanism and target antigen remains unknown.


Asunto(s)
Glomerulonefritis Membranosa , Trasplante de Células Madre Hematopoyéticas , Masculino , Humanos , Persona de Mediana Edad , Complejo Antígeno-Anticuerpo , Trasplante de Células Madre Hematopoyéticas/efectos adversos , Riñón , Diagnóstico Diferencial
17.
Mol Ther ; 31(10): 3052-3066, 2023 Oct 04.
Artículo en Inglés | MEDLINE | ID: mdl-37608549

RESUMEN

Acute kidney injury (AKI) is a critical clinical condition that causes kidney fibrosis, and it currently lacks specific treatment options. In this research, we investigate the role of the SENP1-Sirt3 signaling pathway and its correlation with mitochondrial dysfunction in proximal tubular epithelial cells (PTECs) using folic acid (FA) and ischemia-reperfusion-induced (IRI) AKI models. Our findings reveal that Sirt3 SUMOylation site mutation (Sirt3 KR) or pharmacological stimulation (metformin) protected mice against AKI and subsequent kidney inflammation and fibrosis by decreasing the acetylation level of mitochondrial SOD2, reducing mitochondrial reactive oxygen species (mtROS), and subsequently restoring mitochondrial ATP level, reversing mitochondrial morphology and alleviating cell apoptosis. In addition, AKI in mice was similarly alleviated by reducing mtROS levels using N-acetyl-L-cysteine (NAC) or MitoQ. Metabolomics analysis further demonstrated an increase in antioxidants and metabolic shifts in Sirt3 KR mice during AKI, compared with Sirt3 wild-type (WT) mice. Activation of the AMPK pathway using metformin promoted the SENP1-Sirt3 axis and protected PTECs from apoptosis. Hence, the augmented deSUMOylation of Sirt3 in mitochondria, activated through the metabolism-related AMPK pathway, protects against AKI and subsequently mitigated renal inflammation and fibrosis through Sirt3-SOD2-mtROS, which represents a potential therapeutic target for AKI.

18.
Artículo en Inglés | MEDLINE | ID: mdl-37204952

RESUMEN

As a complex neural network system, the brain regions and genes collaborate to effectively store and transmit information. We abstract the collaboration correlations as the brain region gene community network (BG-CN) and present a new deep learning approach, such as the community graph convolutional neural network (Com-GCN), for investigating the transmission of information within and between communities. The results can be used for diagnosing and extracting causal factors for Alzheimer's disease (AD). First, an affinity aggregation model for BG-CN is developed to describe intercommunity and intracommunity information transmission. Second, we design the Com-GCN architecture with intercommunity convolution and intracommunity convolution operations based on the affinity aggregation model. Through sufficient experimental validation on the AD neuroimaging initiative (ADNI) dataset, the design of Com-GCN matches the physiological mechanism better and improves the interpretability and classification performance. Furthermore, Com-GCN can identify lesioned brain regions and disease-causing genes, which may assist precision medicine and drug design in AD and serve as a valuable reference for other neurological disorders.

19.
Int J Biol Sci ; 19(4): 1192-1210, 2023.
Artículo en Inglés | MEDLINE | ID: mdl-36923942

RESUMEN

Cisplatin is widely recommended in combination for the treatment of tumors, thus inevitably increasing the incidence of cisplatin-induced acute kidney injury. Mitophagy is a type of mitochondrial quality control mechanism that degrades damaged mitochondria and maintains cellular homeostasis. Ferroptosis, a new modality of programmed cell death, is characterized by iron-dependent phospholipid peroxidation and oxidative membrane damage. However, the role of mitophagy in ferroptosis in kidney disease is unclear. Here, we investigated the mechanism underlying both BNIP3-mediated and PINK1-PARK2-mediated mitophagy-induced attenuation of ferroptosis in cisplatin-induced acute kidney injury. The results showed that cisplatin induced mitochondrial injury, ROS release, intracellular iron accumulation, lipid peroxidation and ferroptosis in the kidney, which were aggravated in Bnip3 knockout, Pink1 knockout or Park2 knockout cisplatin-treated mice. Ferrstatin-1, a synthetic antioxidative ferroptosis inhibitor, rescued iron accumulation, lipid peroxidation and ferroptosis caused by inhibition of mitophagy. Thus, the present study elucidated a novel mechanism by which both BNIP3-mediated and PINK1-PARK2-mediated mitophagy protects against cisplatin-induced renal tubular epithelial cell ferroptosis through the ROS/HO1/GPX4 axis.


Asunto(s)
Lesión Renal Aguda , Ferroptosis , Ratones , Animales , Cisplatino/efectos adversos , Mitofagia/genética , Especies Reactivas de Oxígeno/metabolismo , Células Epiteliales/metabolismo , Lesión Renal Aguda/inducido químicamente , Lesión Renal Aguda/metabolismo , Ratones Noqueados , Proteínas Quinasas/metabolismo
20.
BMC Nephrol ; 24(1): 56, 2023 03 15.
Artículo en Inglés | MEDLINE | ID: mdl-36922798

RESUMEN

BACKGROUND: Impaired renal function was not a recognized indication for renal biopsy. The effects of receiving renal biopsy on the renal functional prognosis for chronic kidney disease (CKD) patients with impaired renal function need to be explored. METHODS: This study retrospectively enrolled 300 renal function impaired CKD patients in Renji Hospital from January 2015 to December 2017, 150 of them received percutaneous renal biopsy while the others did not. The endpoint was ≥ 50% estimated glomerular filtration rate (eGFR) decline from baseline or development of end-stage renal disease (ESRD). Kaplan-Meier analysis with log-rank test was performed to compare the renal survival probability between patients receiving renal biopsy or not. Univariate and multivariate analysis with Cox regression were conducted with predictors of poor renal outcomes in the study cohort. RESULTS: The median follow-up period was 37.6 months. During the follow-up period, the eGFR of the biopsy group increased from 52.2 ± 14.4 to 67.4 ± 37.8 ml/min/1.73 m², but decreased from 55.3 ± 17.1 to 29.8 ± 19.1 ml/min/1.73 m² in the non-biopsy group. Patients who received renal biopsy had significantly higher renal survival probability (P < 0.001). Cox regression analysis revealed that 24-hour urine protein excretion (24 h UPE) more than 1 g/d was an independent predictor for poor renal outcomes in the non-biopsy group but not in the renal biopsy group (HR = 1.719, P = 0.040). CONCLUSION: CKD patients with impaired renal function are recommended to receive renal biopsy to make pathological diagnoses, especially for those with the 24-hour urine protein excretion more than 1 g/d.


Asunto(s)
Fallo Renal Crónico , Insuficiencia Renal Crónica , Humanos , Estudios Retrospectivos , Progresión de la Enfermedad , Estudios Prospectivos , Insuficiencia Renal Crónica/diagnóstico , Pronóstico , Tasa de Filtración Glomerular , Factores de Riesgo
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