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1.
Am J Bot ; : e16319, 2024 Apr 20.
Artigo em Inglês | MEDLINE | ID: mdl-38641926

RESUMO

PREMISE: Endophytic and mycorrhizal fungi are crucial in facilitating plant nutrition acquisition and stress tolerance. In epiphytic habitats, plants face nutrition and water stress, but their roots are mostly nonmycorrhizal and especially lacking in arbuscular mycorrhizal associations. Ophioderma pendulum is an epiphytic fern with a partially mycoheterotrophic lifestyle, likely heavily reliant on symbiotic fungi. To characterize fungal associations in the sporophyte of O. pendulum, we focused on leaves and roots of O. pendulum, seeking to reveal the fungal communities in these organs. METHODS: Roots and leaves from O. pendulum in a subtropical forest were examined microscopically to observe the morphology of fungal structures and determine the percentage of various fungal structures in host tissues. Fungal composition was profiled using metabarcoding techniques that targeted ITS2 of the nuclear ribosomal DNA. RESULTS: Roots were consistently colonized by arbuscular mycorrhizal fungi (Glomeromycota), especially Acaulospora. Unlike previous findings on epiphytic ferns, dark septate endophytes were rare in O. pendulum roots. Leaves were predominantly colonized by Ascomycota fungi, specifically the classes Dothideomycetes (46.88%), Eurotiomycetes (11.51%), Sordariomycetes (6.23%), and Leotiomycetes (6.14%). Across sampling sites, fungal community compositions were similar in the roots but differed significantly in the leaves. CONCLUSIONS: Ophioderma pendulum maintains stable, single-taxon-dominant communities in the roots, primarily featuring arbuscular mycorrhizal fungi, whereas the leaves may harbor opportunistic fungal colonizers. Our study underlines the significance of mycorrhizal fungi in the adaptation of epiphytic ferns.

2.
J Ginseng Res ; 48(2): 129-139, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38465219

RESUMO

Liver diseases are a significant global health burden and are among the most common diseases. Ginssennoside Rg3 (Rg3), which is one of the most abundant ginsenosides, has been found to have significant preventive and therapeutic effects against various types of diseases with minimal side effects. Numerous studies have demonstrated the significant preventive and therapeutic effects of Rg3 on various liver diseases such as viral hepatitis, acute liver injury, nonalcoholic liver diseases (NAFLD), liver fibrosis and hepatocellular carcinoma (HCC). The underlying molecular mechanism behind these effects is attributed to apoptosis, autophagy, antioxidant, anti-inflammatory activities, and the regulation of multiple signaling pathways. This review provides a comprehensive description of the potential molecular mechanisms of Rg3 in the development of liver diseases. The article focuses on the regulation of apoptosis, oxidative stress, autophagy, inflammation, and other related factors. Additionally, the review discusses combination therapy and liver targeting strategy, which can accelerate the translation of Rg3 from bench to bedside. Overall, this article serves as a valuable reference for researchers and clinicians alike.

3.
Inflammopharmacology ; 32(2): 975-989, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38429613

RESUMO

Fibrosis is a prevailing pathology in chronic diseases and accounts for 45% of deaths in developed countries. This condition is primarily identified by the transformation of fibroblasts into myofibroblasts and the overproduction of extracellular matrix (ECM) by myofibroblasts. Pterostilbene (PTS) is a natural analogue of resveratrol and is most commonly found in blueberries. Research has shown that PTS exerts a wide range of pharmacological effects, such as antioxidant, anti-inflammatory, and anticancer effects. As a result, PTS has the potential to prevent and cure numerous diseases. Emerging evidence has indicated that PTS can alleviate myocardial fibrosis, renal fibrosis, pulmonary fibrosis, hepatic fibrosis, and colon fibrosis via the inhibition of inflammation, oxidative stress, and fibrogenesis effects in vivo and in vitro, and the potential mechanisms are linked to various pathways, including transforming growth factor-ß1 (TGF-ß1)/small mother against decapentaplegic proteins (Smads) signalling, the reactive oxygen species (ROS)-driven Pitx2c/mir-15b pathway, nuclear factor kappa B (NF-κB) signalling, Kelch-like epichlorohydrin-associated protein-1 (Keap-1)/NF-E2-related factor-2 (Nrf2) cascade, the NLR family pyridine structure domain 3 (NLRP3) pathway, the Janus kinase-2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway, and the Src/STAT3 pathway. In this review, we comprehensively summarize the antifibrotic effects of PTS both in vivo and in vitro and the pharmacological mechanisms, pharmacokinetics, and toxicology of PTS and provide insights into and strategies for exploring promising agents for the treatment of fibrosis.


Assuntos
Estresse Oxidativo , Fibrose Pulmonar , Humanos , Fibrose , Fibrose Pulmonar/tratamento farmacológico , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Antioxidantes/metabolismo , Cirrose Hepática/metabolismo
4.
Technol Health Care ; 2024 Jan 25.
Artigo em Inglês | MEDLINE | ID: mdl-38306070

RESUMO

BACKGROUND: Mechanical ventilation (MV) is a crucial intervention for the support of patients with acute and severe respiratory failure in modern intensive care medicine. However, the mechanical forces resulting from the interplay between the ventilator and the respiratory system may cause pulmonary injury. OBJECTIVE: To compare the effects of high-flow nasal cannula (HFNC) therapy and other oxygen therapy modalities on the risk of endotracheal reintubation in mechanically ventilated patients after extubation in the intensive care unit (ICU). METHODS: An electronic search was carried out across various databases including PubMed, Embase, Ovid, Medline, Cochrane Library, Embase, VIP, and Wanfang. The objective of this search was to locate prospective randomized controlled trials that examined the effects of multiple oxygen therapy approaches on the incidence of reintubation in patients in the ICU after undergoing mechanical ventilation. The meta package in R language was used to analyze parameters adopted by the included studies such as reintubation rate, mortality rate, and length of hospital stay. RESULTS: This study enrolled 22 articles, involving 4,160 participants, with 2,061 in the study group and 2,099 in the control group. Among these, 20 articles presented data on the reintubation rate of the patients included with an odds ratio (OR) of 0.90 (95% CI: 0.74, 1.09) for HFNC and an OR of 1.77 (95% CI: 0.93, 3.38) for HFNC in the chronic obstructive pulmonary disease (COPD) subgroup. Moreover, 10 articles assessed the incidence of respiratory failure after extubation, revealing an OR for HFNC was 0.68 (95% CI: 0.55, 0.84) using a fixed-effects model. Nine articles addressed ICU mortality, while 13 pieces of literature examined hospital mortality. HFNC showed no significant impact on either ICU mortality or hospital mortality. CONCLUSION: HFNC therapy markedly reduces the incidence of respiratory failure in mechanically ventilated patients following extubation in the ICU. Furthermore, it specifically reduces the risk of reintubation in patients diagnosed with COPD.

5.
Clin Chim Acta ; 554: 117795, 2024 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-38262496

RESUMO

BACKGROUND: Hematuria is a common condition in clinical practice of pediatric patients. It is related to a wide spectrum of disorders and has high heterogeneity both clinically and genetically, which contributes to challenges of diagnosis and lead many pediatric patients with hematuria not to receive accurate diagnosis and early management. METHODS: In this single center study, 42 children with hematuria were included in Tianjin Children's Hospital between 2019 and 2020. We analyzed the clinical information and performed WES (Whole exome sequencing) for all cases. Then the classification of identified variants was performed according to the American College of Medical Genetics and Genomics (ACMG) guidelines for interpreting sequence variants. For the fragment deletion, qPCR was performed to validate and confirm the inherited pattern. RESULTS: For the 42 patients, 16 cases had gross hematuria and 26 had microscopic hematuria. Molecular genetic causes were uncovered in 9 (21.4%) children, including 7 with Alport syndrome (AS), one with polycystic nephropathy and one with lipoprotein glomerulopathy. The genetic causes for other patients were not related with hematuria. CONCLUSIONS: WES is a rapid and effective way to evaluate patients with hematuria. The analysis of genotype-phenotype correlations of patients with AS indicated that severe variants were associated with early kidney failure. Secondary findings were not rare in Chinese children, thus the clinician should pay more attention to the clinical interpretation of sequencing results and properly interaction with patients and their family.


Assuntos
Hematúria , Nefropatias , Criança , Humanos , Hematúria/diagnóstico , Hematúria/genética , Sequenciamento do Exoma , Genômica , Estudos de Associação Genética
6.
Pediatr Nephrol ; 39(4): 1301-1313, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38165475

RESUMO

A 3-year-old female patient with no significant medical history presented to her pediatrician with foamy urine. Initial testing revealed moderate proteinuria on qualitative testing, although she was incidentally noted to have severe hypertension (240/200 mmHg). Physical examination of the carotid and femoral areas revealed significant systolic vascular murmurs. Labs showed elevated serum creatinine, hypokalemia, metabolic alkalosis, elevated renin and aldosterone and hypercalciuria. Echocardiography identified ventricular hypertrophy. Computed tomography (CT) of the abdomen and magnetic resonance angiography of the head showed multiple tortuous or interrupted arteries and multiple calcifications in the renal sinus area. B-mode ultrasonography suggested thickening of the carotid and femoral artery walls, with numerous spotted calcifications. Genetic testing revealed that ABCC6 had a complex heterozygous mutation (exon 24: c.3340C > T and intron 30: c.4404-1G > A). Our panel of experts reviewed the evaluation of this patient with hypertension, proteinuria, hypercalciuria, and vascular abnormalities as well as the diagnosis and appropriate management of a rare disease.


Assuntos
Hipertensão , Hipopotassemia , Feminino , Humanos , Pré-Escolar , Hipercalciúria/complicações , Hipercalciúria/diagnóstico , Hipercalciúria/genética , Hipertensão/complicações , Hipertensão/diagnóstico , Hipopotassemia/genética , Testes Genéticos , Proteinúria/etiologia , Proteinúria/genética
7.
Pharmacol Res ; 199: 106957, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-37820856

RESUMO

SIRT1 is a highly conserved nicotinamide adenine dinucleotide (NAD+)-dependent histone deacetylase. It is involved in the regulation of various pathophysiological processes, including cell proliferation, survival, differentiation, autophagy, and oxidative stress. Therapeutic activation of SIRT1 protects the heart and cardiomyocytes from pathology-related stress, particularly myocardial ischemia/reperfusion (I/R). Autophagy is an important metabolic pathway for cell survival during energy or nutrient deficiency, hypoxia, or oxidative stress. Autophagy is a double-edged sword in myocardial I/R injury. The activation of autophagy during the ischemic phase removes excess metabolic waste and helps ensure cardiomyocyte survival, whereas excessive autophagy during reperfusion depletes the cellular components and leads to autophagic cell death. Increasing research on I/R injury has indicated that SIRT1 is involved in the process of autophagy and regulates myocardial I/R. SIRT1 regulates autophagy through various pathways, such as the deacetylation of FOXOs, ATGs, and LC3. Recent studies have confirmed that SIRT1-mediated autophagy plays different roles at different stages of myocardial I/R injury. By targeting the mechanism of SIRT1-mediated autophagy at different stages of I/R injury, new small-molecule drugs, miRNA activators, or blockers can be developed. For example, resveratrol, sevoflurane, quercetin, and melatonin in the ischemic stage, coptisine, curcumin, berberine, and some miRNAs during reperfusion, were involved in regulating the SIRT1-autophagy axis, exerting a cardioprotective effect. Here, we summarize the possible mechanisms of autophagy regulation by SIRT1 in myocardial I/R injury and the related molecular drug applications to identify strategies for treating myocardial I/R injury.


Assuntos
Doença da Artéria Coronariana , Isquemia Miocárdica , Traumatismo por Reperfusão Miocárdica , Humanos , Traumatismo por Reperfusão Miocárdica/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Isquemia Miocárdica/metabolismo , Miócitos Cardíacos/metabolismo , Doença da Artéria Coronariana/metabolismo , Reperfusão , Autofagia , Apoptose
8.
Adv Sci (Weinh) ; 11(6): e2307297, 2024 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-38044294

RESUMO

When spin-orbit coupling (SOC) is absent, all proposed half-metals with twofold degenerate nodal points at the K (or K') point in 2D materials are classified as "Dirac half-metals" owing to the way graphene is utilized in the earliest studies. Actually, each band crossing point at the K or K' point is described by a 2D Weyl Hamiltonian with definite chirality; hence, it should be a Weyl point. To the best of its knowledge, there have not yet been any reports of a genuine (i.e., fourfold degenerate) 2D Dirac point half-metal. In this work, using first-principles calculations, it proposes for the first time that the 2D d0 -type ferromagnet Mg4 N4 is a genuine 2D Dirac half-metal candidate with a fourfold degenerate Dirac point at the S high-symmetry point, intrinsic magnetism, a high Curie temperature, 100% spin polarization, topology robust under the SOC and uniaxial and biaxial strains, and spin-polarized edge states. This work can serve as a starting point for future predictions of intrinsically magnetic materials with genuine 2D Dirac points, which will aid the frontier of topo-spintronics research in 2D systems.

9.
Biochem Genet ; 2023 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-37952039

RESUMO

SLC4A4 variants are the etiologies of inherited proximal renal tubular acidosis (pRTA), which results in metabolic acidosis, hypokalemia, glaucoma, band keratopathy, and cataract. This study aims to characterize SLC4A4 variant and uniparental isodisomy of chromosome 4 in a patient, and analyse the functional characterization of SLC4A4 variants. This study analyzed renal tubular acidosis disease genes by whole exome sequencing (WES). H3M2 algorithm was used to analyze the run of homozygosity region in chromosomal regions in trio-WES data. The pathogenicity analysis of variants was performed using bioinformatics tools. Additionally, protein stability was analyzed by cycloheximide chase assay. Whole-cell patch clamping was used to examine the electrophysiological properties of NBCe1-A. A novel homozygous SLC4A4 variant was identified in the patient: a missense variant c.496C > T, p. Arg166Trp (NM_003759.4). But the father was heterozygous variant carrier, and the mother did not detect the variant. The H3M2 and UPDio algorithm revealed paternal uniparental isodisomy on chromosome 4 in the patient. SIFT, Poly Phen-2, FATHMM and Mutant Taster showed that the variant might be pathogenic. The tertiary structure analysis showed that the variant could cause structural damage to NBCe1 protein. Foldx results showed that the protein stability of the variant was slightly reduced. Cycloheximide chase assay demonstrated that the variant affects protein stability. The result of electrophysiological studies showed that the variant altered Na+/HCO3- cotransport activity of protein. In conclusion, the study is the first to report a pRTA patient with Arg166Trp variant with UPiD (4) pat and analyze the function of Arg166Trp variant.

10.
J Phys Condens Matter ; 35(49)2023 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-37625416

RESUMO

The phase transition of vanadium dioxide brings huge change in its optical property, which is well used in thermochromic window, fixed-temperature heat sensor, laser protection and other fields. Tunable phase transition temperature is one key for its wide applications. In this paper we verified a new simple method to reduce phase transition temperature. A coordination effect of ascorbic acid on VO2powder reduces its phase transition temperature to about 32 °C. This simple method offers a new efficient option to deal with VO2, which may dramatically promote the applications of VO2.

11.
J Phys Condens Matter ; 35(47)2023 Aug 29.
Artigo em Inglês | MEDLINE | ID: mdl-37557886

RESUMO

In this letter, by measuring resistivity and magnetization with magnetic fieldHrotated inabplane and currentIalongcaxis, we studied the magnetic and electronic structure symmetry of frustrated topological bilayer Kagome ferromagnet Fe3Sn2. We observed that the curves of the resistivity and magnetization both showed broken two-fold symmetry from 5 K to 380 K. The further analysis indicates that there is a close causality between the spin arrangement and the electronic states in Fe3Sn2even above room temperature. These phenomena are closely related to the change in spin-orbit coupling (SOC) under the magnetic field. Our experimental results suggest that Fe3Sn2is an ideal platform to study the influence of spin arrangement on electronic state in topological materials and can also be used to design next generation magnetic devices by modulating SOC at external magnetic field.

12.
Org Lett ; 25(30): 5563-5568, 2023 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-37477589

RESUMO

A redox-neutral copper-catalyzed cascade reaction involving alkoxyl radical-mediated ring expansion/1,4-difunctionalization of 1,3-enynes was developed, offering a straightforward approach to the tetra-substituted allenes with macrolactone, CN, and CF3 functional groups. Remarkably, incorporation of the NH2 group onto the 1,3-enyne moiety enabled further cyclization to give a unique scaffold containing a lactone and an indole moiety.

13.
Sensors (Basel) ; 23(10)2023 May 17.
Artigo em Inglês | MEDLINE | ID: mdl-37430753

RESUMO

Hyperspectral band selection plays an important role in overcoming the curse of dimensionality. Recently, clustering-based band selection methods have shown promise in the selection of informative and representative bands from hyperspectral images (HSIs). However, most existing clustering-based band selection methods involve the clustering of original HSIs, limiting their performance because of the high dimensionality of hyperspectral bands. To tackle this problem, a novel hyperspectral band selection method termed joint learning of correlation-constrained fuzzy clustering and discriminative non-negative representation for hyperspectral band selection (CFNR) is presented. In CFNR, graph regularized non-negative matrix factorization (GNMF) and constrained fuzzy C-means (FCM) are integrated into a unified model to perform clustering on the learned feature representation of bands rather than on the original high-dimensional data. Specifically, the proposed CFNR aims to learn the discriminative non-negative representation of each band for clustering by introducing GNMF into the model of the constrained FCM and making full use of the intrinsic manifold structure of HSIs. Moreover, based on the band correlation property of HSIs, a correlation constraint, which enforces the similarity of clustering results between neighboring bands, is imposed on the membership matrix of FCM in the CFNR model to obtain clustering results that meet the needs of band selection. The alternating direction multiplier method is adopted to solve the joint optimization model. Compared with existing methods, CFNR can obtain a more informative and representative band subset, thus can improve the reliability of hyperspectral image classifications. Experimental results on five real hyperspectral datasets demonstrate that CFNR can achieve superior performance compared with several state-of-the-art methods.

14.
Biomed Pharmacother ; 165: 115191, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-37487440

RESUMO

ß-hydroxybutyrate (ß-HB), the most abundant ketone body, is produced primarily in the liver and acts as a substitute energy fuel to provide energy to extrahepatic tissues in the event of hypoglycemia or glycogen depletion. We now have an improved understanding of ß-HB as a signal molecule and epigenetic regulatory factor as a result of intensive research over the last ten years. Because ß-HB regulates various physiological and pathological processes, it may have a potential role in the treatment of metabolic diseases. The liver is the most significant metabolic organ, and the part that ß-HB plays in liver disorders is receiving increasing attention. In this review, we summarize the therapeutic effects of ß-HB on liver diseases and its underlying mechanisms of action. Moreover, we explore the prospects of exogenous supplements and endogenous ketosis including fasting, caloric restriction (CR), ketogenic diet (KD), and exercise as adjuvant nutritional therapies to protect the liver from damage and provide insights and strategies for exploring the treatment of various liver diseases.


Assuntos
Dieta Cetogênica , Cetose , Hepatopatias , Humanos , Ácido 3-Hidroxibutírico/metabolismo , Corpos Cetônicos/metabolismo , Hepatopatias/tratamento farmacológico
15.
Nanoscale ; 15(30): 12518-12529, 2023 Aug 03.
Artigo em Inglês | MEDLINE | ID: mdl-37278298

RESUMO

Despite aggressive treatments, including surgery, chemotherapy and radiotherapy, the prognosis of glioblastoma (GBM) remains poor, and tumor recurrence is inevitable. The FDA-approved CDK4/6 inhibitor palbociclib (PB) showed interesting anti-GBM effects, but its brain penetration is limited by the blood-brain barrier. The aim of this project is to find whether the cellulose-based hydrogel via in situ injection could provide an alternative route to PB brain delivery and generate sufficient drug exposure in orthotopic GBM. In brief, PB was encapsulated in a cellulose nanocrystal network structure crosslinked by polydopamine via divalent Cu2+ and hexadecylamine. The formed hydrogel (PB@PH/Cu-CNCs) exhibited sustained drug retention and acid-responsive network de-polymerization for controlled release in vivo. Specifically, the released Cu2+ catalyzed a Fenton-like reaction to generate reactive oxygen species (ROS), which was further enhanced by PB, and consequently, irreversible senescence and apoptosis were induced in GBM cells. Finally, PB@PH/Cu-CNCs demonstrated a more potent anti-GBM effect than those treated with free PB or PH/Cu-CNCs (drug-free hydrogel) in cultured cells or in an orthotopic glioma model. These results prove that the injection of the PB-loaded hydrogel in situ is an effective strategy to deliver the CDK4/6 inhibitor into the brain and its anti-GBM effect can be further enhanced by combining Cu2+-mediated Fenton-like reaction.


Assuntos
Glioblastoma , Celulose/química , Hidrogéis/química , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Humanos , Feminino , Animais , Camundongos , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Concentração de Íons de Hidrogênio , Proliferação de Células , Inibidores de Proteínas Quinases/química , Inibidores de Proteínas Quinases/uso terapêutico , Senescência Celular , Apoptose , Espécies Reativas de Oxigênio/metabolismo
16.
Clin Exp Metastasis ; 40(4): 339-356, 2023 08.
Artigo em Inglês | MEDLINE | ID: mdl-37326719

RESUMO

Cetuximab, an epidermal growth factor receptor (EGFR) inhibitor, is extensively used for clinical therapy in KRAS wild-type colorectal cancer (CRC) patients. However, some patients still cannot get benefit from the therapy, because metastasis and resistance occur frequently after cetuximab treatment. New adjunctive therapy is urgently needed to suppress metastasis of cetuximab-treated CRC cells. In this study, we used two KRAS wild-type CRC cells, HT29 and CaCo2, to investigate whether platycodin D, a triterpenoid saponin isolated from Chinese medicinal herb Platycodon grandifloras, is able to suppress the metastasis of cetuximab-treated CRC. Label-free quantitative proteomics analyses showed that platycodin D but not cetuximab significantly inhibited expression of ß-catenin in both CRC cells, and suggested that platycodin D counteracted the inhibition effect of cetuximab on cell adherence and functioned in repressing cell migration and invasion. Western blot results showed that single platycodin D treatment or combined platycodin D and cetuximab enhanced inhibition effects on expressions of key genes in Wnt/ß-catenin signaling pathway, including ß-catenin, c-Myc, Cyclin D1 and MMP-7, compared to single cetuximab treatment. Scratch wound-healing and transwell assays showed that platycodin D combined with cetuximab suppressed migration and invasion of CRC cells, respectively. Pulmonary metastasis model of HT29 and CaCo2 in nu/nu nude mice consistently showed that combined treatment using platycodin D and cetuximab inhibited metastasis significantly in vivo. Our findings provide a potential strategy to inhibit CRC metastasis during cetuximab therapy by addition of platycodin D.


Assuntos
Neoplasias Colorretais , Saponinas , Triterpenos , Humanos , Animais , Camundongos , Cetuximab/farmacologia , Cetuximab/metabolismo , Cetuximab/uso terapêutico , Proteínas Proto-Oncogênicas p21(ras)/genética , Células CACO-2 , beta Catenina , Camundongos Nus , Saponinas/farmacologia , Saponinas/uso terapêutico , Triterpenos/farmacologia , Triterpenos/uso terapêutico , Via de Sinalização Wnt , Neoplasias Colorretais/tratamento farmacológico , Neoplasias Colorretais/genética , Neoplasias Colorretais/patologia , Linhagem Celular Tumoral , Proliferação de Células , Movimento Celular/genética
17.
Nephron ; 147(9): 572-582, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36878198

RESUMO

Nephronophthisis is an autosomal recessive cystic kidney disease characterized by tubular injury and commonly results in kidney failure. We reported a case of 4-year-old Chinese boy presented with severe anemia, kidney, and liver dysfunction. Whole exome sequencing (WES) was performed to identify the candidate variant with a negative result initially. After complete collection of clinical information, reanalysis of WES identified a homozygous NPHP3 variant c.3813-3A>G (NM_153240.4). The effect on mRNA splicing of the intronic variant was predicted through software (three in silico splice tools). Furthermore, in vitro minigene assay was conducted to validate the predicted deleterious effects of the intronic variant. All of the splice prediction programs and minigene assay indicated that the variant had an impact on the normal splicing pattern of NPHP3. Our study confirmed the effect of the c.3813-3A>G variant on NPHP3 splicing in vitro, which gives additional evidence for the clinical significance of the variant and provides a basis for genetic diagnosis of nephronophthisis 3. In addition, we think that it is essential to reanalyze WES data after the complete clinical information collection to avoid missing some important candidate variants.


Assuntos
População do Leste Asiático , Doenças Renais Policísticas , Masculino , Humanos , Pré-Escolar , Sequenciamento do Exoma , Mutação
18.
Adv Sci (Weinh) ; 10(9): e2206106, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36683184

RESUMO

Skyrmions are swirling spin textures with topological characters promising for future spintronic applications. Skyrmionic devices typically rely on the electrical manipulation of skyrmions with a circular shape. However, manipulating elliptically distorted skyrmions can lead to numerous exotic magneto-electrical functions distinct from those of conventional circular skyrmions, significantly broadening the capability to design innovative spintronic devices. Despite the promising potential, its experimental realization so far remains elusive. In this study, the current-driven dynamics of the elliptically distorted skyrmions in geometrically confined magnet Fe3 Sn2 is experimentally explored. This study finds that the elliptical skyrmions can reversibly split into smaller-sized circular skyrmions at a current density of 3.8 × 1010 A m-2 with the current injected along their minor axis. Combined experiments with micromagnetic simulations reveal that this dynamic behavior originates from a delicate interplay of the spin-transfer torque, geometrical confinement, and pinning effect, and strongly depends on the ratio of the major axis to the minor axis of the elliptical skyrmions. The results indicate that the morphology is a new degree of freedom for manipulating the current-driven dynamics of skyrmions, providing a compelling route for the future development of spintronic devices.

19.
Pharmacol Res ; 188: 106657, 2023 02.
Artigo em Inglês | MEDLINE | ID: mdl-36682437

RESUMO

Fibrosis is the end-stage pathological manifestation of many chronic diseases. Infiltration of inflammatory cells and activation of myofibroblasts are the most prominent features of fibrosis, with excessive deposition of extracellular matrix (ECM) in tissues leading to organ tissue damage, which eventually progresses to organ failure and leads to high mortality rates. At present, a large number of studies have been conducted on tissue fibrosis, and the pathological mechanism of fibrosis development has generally been recognized. However, the prevention and treatment of fibrosis is still an unsolved problem, and a shortage of drugs that can be used in the clinic persists. Astaxanthin (ASTX), a carotenoid, is widely known for its strong antioxidant capacity. ASTX also has other biological properties, such as anti-inflammatory, antiaging and anticancer properties. Recently, many papers have reported that ASTX inhibits the occurrence and development of fibrosis by regulating signaling molecular pathways, such as transforming growth factor-ß/small mother against decapentaplegic protein (TGF-ß1/Smad), sirtuin 1 (SIRT1), nuclear factor kappa-B (NF-κB), microRNA, nuclear factor-E2-related factor 2/antioxidant response element (Nrf 2/ARE) and reactive oxygen species (ROS) pathways. By targeting these molecular signaling pathways, ASTX may become a potential drug for the treatment of fibrotic diseases. In this review, we summarize the therapeutic effects of ASTX on organ fibrosis and its underlying mechanisms of action. By reviewing the results from in vitro and in vivo studies, we analyzed the therapeutic prospects of ASTX for various fibrotic diseases and provided insights into and strategies for exploring new drugs for the treatment of fibrosis.


Assuntos
Fator de Crescimento Transformador beta1 , Xantofilas , Humanos , Fibrose , Xantofilas/farmacologia , Xantofilas/uso terapêutico , Fator de Crescimento Transformador beta1/metabolismo , Fator de Crescimento Transformador beta/metabolismo , Matriz Extracelular/metabolismo
20.
J Occup Environ Med ; 65(1): e10-e15, 2023 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-36253926

RESUMO

OBJECTIVE: The aims of this study were to determine the association of skeletal muscle mass with three cardiovascular risk factors and explore a simple and clinically feasible indicator for identifying high-risk groups of cardiovascular diseases in occupational sedentary population. METHODS: We recruited 7316 occupational sedentary participants older than 18 years from the Health Management Center of Tianjin Union Medical Center. Age-adjusted logistic regression was used to analyze the association between skeletal muscle mass index (SMI) and cardiovascular risk factors. RESULTS: There were significant positive associations between SMI, especially arm SMI, and cardiovascular risk factors in both male and female subjects (odds ratio, 1.28 to 5.02; P < 0.001). CONCLUSIONS: Our findings suggest that measurements of skeletal muscle mass, particularly in the arms, may help identify individuals at high risk for cardiovascular disease in an occupationally sedentary population.


Assuntos
Doenças Cardiovasculares , Sarcopenia , Humanos , Masculino , Feminino , Músculo Esquelético , Sarcopenia/epidemiologia , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/patologia , Estudos Transversais , Fatores de Risco , Fatores de Risco de Doenças Cardíacas
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