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1.
Environ Pollut ; 356: 124253, 2024 Jun 06.
Artículo en Inglés | MEDLINE | ID: mdl-38851378

RESUMEN

Bioaugmentation techniques still show drawbacks in the cleanup of total petroleum hydrocarbons (TPHs) from petroleum-contaminated site soil. Herein, this study explored high-performance immobilized bacterial pellets (IBPs) embed Microbacterium oxydans with a high degrading capacity, and developed a controlled-release oxygen composite (CROC) that allows the efficient, long-term release of oxygen. Tests with four different microcosm incubations were performed to assess the effects of IBPs and CROC on the removal of TPHs from petroleum-contaminated site soil. The results showed that the addition of IBPs and/or CROC could significantly promote the remediation of TPHs in soil. A CROC only played a significant role in the degradation of TPHs in deep soil. The combined application of IBPs and CROC had the best effect on the remediation of deep soil, and the removal rate of TPHs reached 70%, which was much higher than that of nature attenuation (13.2%) and IBPs (43.0%) or CROC (31.9%) alone. In particular, the CROC could better promote the degradation of heavy distillate hydrocarbons (HFAs) in deep soil, and the degradation rates of HFAs increased from 6.6% to 33.2%-21.0% and 67.9%, respectively. In addition, the IBPs and CROC significantly enhanced the activity of dehydrogenase, catalase, and lipase in soil. Results of the enzyme activity were the same as that of TPH degradation. The combined application of IBPs and CROC not only increased the microbial abundance and diversity of soil, but also significantly enhanced the enrichment of potential TPH-biodegrading bacteria. M. oxydans was dominant in AP (bioaugmentation with addition of IBPs) and APO (bioaugmentation with the addition of IBPs and CROC) microcosms that added IBPs. Overall, the IBPs and CROC developed in this study provide a novel option for the combination of bioaugmentation and biostimulation for remediating organic pollutants in soil.

2.
Kidney Res Clin Pract ; 43(3): 263-273, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38863384

RESUMEN

With an increasing aging population, the mean age of patients with end-stage kidney disease (ESKD) is globally increasing. However, the current clinical status of elderly patients undergoing hemodialysis (HD) is rarely reported in Korea. The current study analyzed the clinical features and trends of older patients undergoing HD from the Korean Renal Data System (KORDS) database. The patients were divided into three groups according to age: <65 years (the young group), n = 50,591 (35.9%); 65-74 years (the younger-old group), n = 37,525 (26.6%); and ≥75 years (the older-old group), n = 52,856 (37.5%). The proportion of older-old group undergoing HD significantly increased in incidence and decreased in prevalence from 2013 to 2022. The median levels of hemoglobin, serum creatinine, albumin, calcium, phosphorus, and intact parathyroid hormone significantly decreased in the older-old group. The proportions of arteriovenous fistula creation and left forearm placement showed decreased trends with age. Although the utilization of low surface area dialyzers increased with age, the dialysis adequacy, including urea reduction ratio and Kt/V was within acceptable range in the older-old group on HD. Over the past 20 years, the mortality rate in the older-old group has increased, with cardiovascular diseases decreasing and infectious diseases increasing. The incidence of elderly patients undergoing HD has increased over time, but the high mortality of the older-old group needs to be solved. Therefore, it is imperative to develop holistic strategies based on age and individual needs for patients with ESKD.

3.
Cell Transplant ; 33: 9636897241248956, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38715279

RESUMEN

Heart failure remains the leading cause of human death worldwide. After a heart attack, the formation of scar tissue due to the massive death of cardiomyocytes leads to heart failure and sudden death in most cases. In addition, the regenerative ability of the adult heart is limited after injury, partly due to cell-cycle arrest in cardiomyocytes. In the current post-COVID-19 era, urgently authorized modified mRNA (modRNA) vaccines have been widely used to prevent severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. Therefore, modRNA-based protein replacement may act as an alternative strategy for improving heart disease. It is a safe, effective, transient, low-immunogenic, and integration-free strategy for in vivo protein expression, in addition to recombinant protein and stem-cell regenerative therapies. In this review, we provide a summary of various cardiac factors that have been utilized with the modRNA method to enhance cardiovascular regeneration, cardiomyocyte proliferation, fibrosis inhibition, and apoptosis inhibition. We further discuss other cardiac factors, modRNA delivery methods, and injection methods using the modRNA approach to explore their application potential in heart disease. Factors for promoting cardiomyocyte proliferation such as a cocktail of three genes comprising FoxM1, Id1, and Jnk3-shRNA (FIJs), gp130, and melatonin have potential to be applied in the modRNA approach. We also discuss the current challenges with respect to modRNA-based cardiac regenerative medicine that need to be overcome to apply this approach to heart disease. This review provides a short description for investigators interested in the development of alternative cardiac regenerative medicines using the modRNA platform.


Asunto(s)
Miocitos Cardíacos , ARN Mensajero , Regeneración , Humanos , Miocitos Cardíacos/metabolismo , Miocitos Cardíacos/citología , Animales , ARN Mensajero/genética , ARN Mensajero/metabolismo , COVID-19/terapia , SARS-CoV-2/genética , Insuficiencia Cardíaca/terapia
4.
Microb Cell Fact ; 23(1): 134, 2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724934

RESUMEN

BACKGROUND: Lovastatin has widespread applications thanks to its multiple pharmacological effects. Fermentation by filamentous fungi represents the major way of lovastatin production. However, the current lovastatin productivity by fungal fermentation is limited and needs to be improved. RESULTS: In this study, the lovastatin-producing strains of Aspergillus terreus from marine environment were screened, and their lovastatin productions were further improved by genetic engineering. Five strains of A. terreus were isolated from various marine environments. Their secondary metabolites were profiled by metabolomics analysis using Ultra Performance Liquid Chromatography-Mass spectrometry (UPLC-MS) with Global Natural Products Social Molecular Networking (GNPS), revealing that the production of secondary metabolites was variable among different strains. Remarkably, the strain of A. terreus MJ106 could principally biosynthesize the target drug lovastatin, which was confirmed by High Performance Liquid Chromatography (HPLC) and gene expression analysis. By one-factor experiment, lactose was found to be the best carbon source for A. terreus MJ106 to produce lovastatin. To improve the lovastatin titer in A. terreus MJ106, genetic engineering was applied to this strain. Firstly, a series of strong promoters was identified by transcriptomic and green fluorescent protein reporter analysis. Then, three selected strong promoters were used to overexpress the transcription factor gene lovE encoding the major transactivator for lov gene cluster expression. The results revealed that compared to A. terreus MJ106, all lovE over-expression mutants exhibited significantly more production of lovastatin and higher gene expression. One of them, LovE-b19, showed the highest lovastatin productivity at a titer of 1512 mg/L, which represents the highest production level reported in A. terreus. CONCLUSION: Our data suggested that combination of strain screen and genetic engineering represents a powerful tool for improving the productivity of fungal secondary metabolites, which could be adopted for large-scale production of lovastatin in marine-derived A. terreus.


Asunto(s)
Aspergillus , Fermentación , Ingeniería Genética , Lovastatina , Lovastatina/biosíntesis , Lovastatina/metabolismo , Aspergillus/metabolismo , Aspergillus/genética , Organismos Acuáticos/metabolismo , Organismos Acuáticos/genética
6.
Vaccine X ; 18: 100491, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38746062

RESUMEN

Information regarding the detection perioid of measles vaccine virus (MeVV) RNA in human nasopharyngeal samples and measles-specific antibodies following measles-mumps-rubella (MMR) vaccination is limited. During contact tracing for a measles outbreak at a hospital in Republic of Korea, 4 out of 206 children vaccinated with MMR underwent real-time RT-PCR assay for measles and measles-specific antibodies test. Measles virus RNA was detected in 2 children, all of which was vaccine virus strain RNA (genotype A). In a healthy 27-month-old boy, MeVV RNA was detected 448 days after MMR vaccination. Measles-specific IgM was positive 1097 days following vaccination in a 4-year-old girl. MeVV RNA and measles-specific IgM were detected for a considerable period following primary MMR vaccination. Physicians should exercise caution when interpreting positive RT-PCR results for MeVV or measles-specific IgM from a child with measles-associated symptoms who has been recently vaccinated against measles.

7.
Adv Sci (Weinh) ; : e2309786, 2024 May 17.
Artículo en Inglés | MEDLINE | ID: mdl-38760898

RESUMEN

A universal approach for enhancing water affinity in polymer photocatalysts by covalently attaching hydrophilic photocrosslinkers to polymer chains is presented. A series of bisdiazirine photocrosslinkers, each comprising bisdiazirine photophores linked by various aliphatic (CL-R) or ethylene glycol-based bridge chains (CL-TEG), is designed to prevent crosslinked polymer photocatalysts from degradation through a safe and efficient photocrosslinking reaction at a wavelength of 365 nm. When employing the hydrophilic CL-TEG as a photocrosslinker with polymer photocatalysts (F8BT), the hydrogen evolution reaction (HER) rate is considerably enhanced by 2.5-fold compared to that obtained using non-crosslinked F8BT photocatalysts, whereas CL-R-based photocatalysts yield HER rates comparable to those of non-crosslinked counterparts. Photophysical analyses including time-resolved photoluminescence and transient absorption measurements reveal that adding CL-TEG accelerates exciton separation, forming long-lived charge carriers. Additionally, the in-depth study using molecular dynamics simulations elucidates the dual role of CL-TEG: it enhances water penetration into the polymer matrix and stabilizes charge carriers after exciton generation against undesirable recombination. Therefore, the strategy highlights endowing a high-permittivity environment within polymer photocatalyst in a controlled manner is crucial for enhancing photocatalytic redox reactivity. Furthermore, this study shows that this hydrophilic crosslinker approach has a broad applicability in general polymer semiconductors and their nanoparticulate photocatalysts.

8.
Cell Rep ; 43(6): 114272, 2024 May 24.
Artículo en Inglés | MEDLINE | ID: mdl-38795348

RESUMEN

Lysine deacetylase inhibitors (KDACis) are approved drugs for cutaneous T cell lymphoma (CTCL), peripheral T cell lymphoma (PTCL), and multiple myeloma, but many aspects of their cellular mechanism of action (MoA) and substantial toxicity are not well understood. To shed more light on how KDACis elicit cellular responses, we systematically measured dose-dependent changes in acetylation, phosphorylation, and protein expression in response to 21 clinical and pre-clinical KDACis. The resulting 862,000 dose-response curves revealed, for instance, limited cellular specificity of histone deacetylase (HDAC) 1, 2, 3, and 6 inhibitors; strong cross-talk between acetylation and phosphorylation pathways; localization of most drug-responsive acetylation sites to intrinsically disordered regions (IDRs); an underappreciated role of acetylation in protein structure; and a shift in EP300 protein abundance between the cytoplasm and the nucleus. This comprehensive dataset serves as a resource for the investigation of the molecular mechanisms underlying KDACi action in cells and can be interactively explored online in ProteomicsDB.

9.
Mol Cancer ; 23(1): 109, 2024 May 20.
Artículo en Inglés | MEDLINE | ID: mdl-38769556

RESUMEN

Breast cancer (BC) is the most frequent malignant cancer diagnosis and is a primary factor for cancer deaths in women. The clinical subtypes of BC include estrogen receptor (ER) positive, progesterone receptor (PR) positive, human epidermal growth factor receptor 2 (HER2) positive, and triple-negative BC (TNBC). Based on the stages and subtypes of BC, various treatment methods are available with variations in the rates of progression-free disease and overall survival of patients. However, the treatment of BC still faces challenges, particularly in terms of drug resistance and recurrence. The study of epigenetics has provided new ideas for treating BC. Targeting aberrant epigenetic factors with inhibitors represents a promising anticancer strategy. The KDM5 family includes four members, KDM5A, KDM5B, KDM5C, and KDMD, all of which are Jumonji C domain-containing histone H3K4me2/3 demethylases. KDM5 proteins have been extensively studied in BC, where they are involved in suppressing or promoting BC depending on their specific upstream and downstream pathways. Several KDM5 inhibitors have shown potent BC inhibitory activity in vitro and in vivo, but challenges still exist in developing KDM5 inhibitors. In this review, we introduce the subtypes of BC and their current therapeutic options, summarize KDM5 family context-specific functions in the pathobiology of BC, and discuss the outlook and pitfalls of KDM5 inhibitors in this disease.


Asunto(s)
Neoplasias de la Mama , Histona Demetilasas , Terapia Molecular Dirigida , Humanos , Femenino , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Neoplasias de la Mama/patología , Neoplasias de la Mama/genética , Neoplasias de la Mama/terapia , Histona Demetilasas/antagonistas & inhibidores , Histona Demetilasas/metabolismo , Histona Demetilasas/genética , Animales , Antineoplásicos/uso terapéutico , Antineoplásicos/farmacología , Epigénesis Genética , Regulación Neoplásica de la Expresión Génica , Histona Demetilasas con Dominio de Jumonji/metabolismo , Histona Demetilasas con Dominio de Jumonji/antagonistas & inhibidores , Histona Demetilasas con Dominio de Jumonji/genética , Biomarcadores de Tumor
10.
Biomolecules ; 14(5)2024 May 12.
Artículo en Inglés | MEDLINE | ID: mdl-38785979

RESUMEN

The balance between ubiquitination and deubiquitination is instrumental in the regulation of protein stability and maintenance of cellular homeostasis. The deubiquitinating enzyme, ubiquitin-specific protease 36 (USP36), a member of the USP family, plays a crucial role in this dynamic equilibrium by hydrolyzing and removing ubiquitin chains from target proteins and facilitating their proteasome-dependent degradation. The multifaceted functions of USP36 have been implicated in various disease processes, including cancer, infections, and inflammation, via the modulation of numerous cellular events, including gene transcription regulation, cell cycle regulation, immune responses, signal transduction, tumor growth, and inflammatory processes. The objective of this review is to provide a comprehensive summary of the current state of research on the roles of USP36 in different pathological conditions. By synthesizing the findings from previous studies, we have aimed to increase our understanding of the mechanisms underlying these diseases and identify potential therapeutic targets for their treatment.


Asunto(s)
Neoplasias , Ubiquitina Tiolesterasa , Humanos , Neoplasias/metabolismo , Neoplasias/genética , Neoplasias/enzimología , Neoplasias/patología , Ubiquitina Tiolesterasa/metabolismo , Ubiquitina Tiolesterasa/genética , Animales , Ubiquitinación , Inflamación/metabolismo , Transducción de Señal , Ubiquitina/metabolismo
11.
Appl Microbiol Biotechnol ; 108(1): 323, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38713233

RESUMEN

Ergot alkaloids (EAs) are a diverse group of indole alkaloids known for their complex structures, significant pharmacological effects, and toxicity to plants. The biosynthesis of these compounds begins with chanoclavine-I aldehyde (CC aldehyde, 2), an important intermediate produced by the enzyme EasDaf or its counterpart FgaDH from chanoclavine-I (CC, 1). However, how CC aldehyde 2 is converted to chanoclavine-I acid (CC acid, 3), first isolated from Ipomoea violacea several decades ago, is still unclear. In this study, we provide in vitro biochemical evidence showing that EasDaf not only converts CC 1 to CC aldehyde 2 but also directly transforms CC 1 into CC acid 3 through two sequential oxidations. Molecular docking and site-directed mutagenesis experiments confirmed the crucial role of two amino acids, Y166 and S153, within the active site, which suggests that Y166 acts as a general base for hydride transfer, while S153 facilitates proton transfer, thereby increasing the acidity of the reaction. KEY POINTS: • EAs possess complicated skeletons and are widely used in several clinical diseases • EasDaf belongs to the short-chain dehydrogenases/reductases (SDRs) and converted CC or CC aldehyde to CC acid • The catalytic mechanism of EasDaf for dehydrogenation was analyzed by molecular docking and site mutations.


Asunto(s)
Aldehídos , Alcaloides de Claviceps , Aldehídos/metabolismo , Aldehídos/química , Dominio Catalítico , Alcaloides de Claviceps/biosíntesis , Alcaloides de Claviceps/química , Alcaloides de Claviceps/metabolismo , Simulación del Acoplamiento Molecular , Mutagénesis Sitio-Dirigida , Oxidación-Reducción , Oxidorreductasas/metabolismo , Oxidorreductasas/genética , Oxidorreductasas/química
12.
Cells ; 13(10)2024 May 16.
Artículo en Inglés | MEDLINE | ID: mdl-38786072

RESUMEN

Spermatogenesis is a highly regulated process dependent on androgen receptor (AR) signaling in Sertoli cells. However, the pathogenic mechanisms of spermatogenic failure, by which loss of AR impairs downstream target genes to affect Sertoli cell function, remain incompletely understood. By using microarray analysis, we identified several AR-regulated genes involved in the maturation of spermatogenesis, including chromodomain Y-like protein (CDYL) and transition proteins 1 (TNP-1), that were significantly decreased in ARKO mouse testes. AR and CDYL were found to co-localize and interact in Sertoli cells. The AR-CDYL complex bound to the promoter regions of TNP1 and modulated their transcriptional activity. CDYL acts as a co-regulator of AR transactivation, and its expression is decreased in the Sertoli cells of human testes from patients with azoospermia. The androgen receptor-chromodomain Y-like protein axis plays a crucial role in regulating a network of genes essential for spermatogenesis in Sertoli cells. Disruption of this AR-CDYL regulatory axis may contribute to spermatogenic failure. These findings provide insights into novel molecular mechanisms targeting the AR-CDYL signaling pathway, which may have implications for developing new therapeutic strategies for male infertility.


Asunto(s)
Receptores Androgénicos , Células de Sertoli , Transducción de Señal , Espermatogénesis , Masculino , Células de Sertoli/metabolismo , Receptores Androgénicos/metabolismo , Receptores Androgénicos/genética , Espermatogénesis/genética , Animales , Humanos , Ratones , Ratones Noqueados , Azoospermia/metabolismo , Azoospermia/genética , Azoospermia/patología , Ratones Endogámicos C57BL , Factores de Transcripción , Proteínas de Homeodominio
13.
Int J Med Sci ; 21(7): 1302-1306, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38818474

RESUMEN

Background: Hyperopia is a significant refractive error in children, often leading to vision impairment. This study aimed to investigate whether partial or full spectacle correction is benefit for hyperopia in preschool-aged children. Methods: A retrospective study was conducted on hyperopic children visited to teaching medical center outpatient clinic between October 2011 and October 2018, and were categorized into three groups: full correction, overcorrection, and undercorrection. The study was approved by the institutional ethical committee of Tri-Service General Hospital. Results: Following a minimum of one-year follow-up period, no statistically significant differences were observed in best-corrected visual acuity (BCVA) among children receiving full, over, or under spectacle correction. Notably, the overcorrection group exhibited a significant reduction in spherical equivalent (SE) compared to both the full and under correction groups, indicating a better SE with spectacle overcorrection. Conclusions: Spectacle overcorrection may offer potential benefits for enhancing SE in preschool children with hyperopia. Nevertheless, further investigation through randomized controlled trials is warranted to establish the validity of this approach and its impact on visual outcomes in this hyperopic pediatric population.


Asunto(s)
Anteojos , Hiperopía , Agudeza Visual , Humanos , Hiperopía/terapia , Hiperopía/fisiopatología , Estudios Retrospectivos , Preescolar , Femenino , Masculino , Refracción Ocular/fisiología , Niño , Resultado del Tratamiento , Estudios de Seguimiento
14.
J Tradit Complement Med ; 14(3): 266-275, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38707917

RESUMEN

Mulberry leaf has been recognized as a traditional Chinese medicinal plant, which was distributed throughout the Asia. The aqueous extract of mulberry leaf extract (MLE) has various biologically active components such as polyphenols and flavonoids. However, the inhibitory effect of MLE in hepatocarcinogenesis is poorly understood. In this study, we determined the role of MLE supplementation in preventing hepatocarcinogenesis in a carcinogen-initiated high-fat diet (HFD)-promoted Sprague-Dawley (SD) rat model. The rats were fed an HFD to induce obesity and spontaneous hepatomas by administering 0.01% diethylnitrosamine (DEN) in their drinking water for 12 weeks (HD group), and also to fed MLE through oral ingestion at daily doses of 0.5%, 1%, or 2%. At the end of the 12-week experimental period, the liver tumors were analyzed to identify markers of oxidative stress and antioxidant enzyme activities, and their serum was analyzed to determine their nutritional status and liver function. Histopathological analysis revealed that MLE supplementation significantly suppressed the severity and incidence of hepatic tumors. Furthermore, compared with the HFD + DEN groups, the expression of protein kinase C (PKC)-α and Rac family small GTPase 1 (Rac1) was lower in the MLE groups. These findings suggest that MLE prevents obesity-enhanced, carcinogen-induced hepatocellular carcinoma development, potentially through the protein kinase C (PKC)α/Rac1 signaling pathway. MLE might be an effective chemoprevention modality for nonalcoholic fatty liver disease (NAFLD)/nonalcoholic steatohepatitis (NASH)-related hepatocarcinogenesis.

15.
Rev Med Suisse ; 20(867): 638-647, 2024 Mar 27.
Artículo en Francés | MEDLINE | ID: mdl-38563538

RESUMEN

Auto-immune bullous diseases (AIBD) are rare in children. Although their pathogenesis is similar to their adult counterpart, there are differences in the clinical presentation. Moreover certain AIBD prevail at certain ages. There are no guidelines for the treatment of AIBD specific for children. In this review the recent literature is summarised with attention to recent data including diagnostic criteria. We also propose a treatment algorithm.


Les maladies bulleuses auto-immunes (MBAI) sont rares chez les enfants. Bien que la pathogenèse soit similaire à celle de l'adulte, il existe des différences concernant la présentation clinique et la prévalence des MBAI selon l'âge. À ce jour, il n'y a pas de recommandations spécifiques pour leur prise en charge chez l'enfant. Dans cet article, nous présentons une revue des données actuelles, des critères diagnostiques et proposons un algorithme de prise en charge.


Asunto(s)
Enfermedades Autoinmunes , Enfermedades Cutáneas Vesiculoampollosas , Niño , Humanos , Algoritmos , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/terapia , Enfermedades Cutáneas Vesiculoampollosas/diagnóstico , Enfermedades Cutáneas Vesiculoampollosas/patología
16.
Work ; 2024 Apr 25.
Artículo en Inglés | MEDLINE | ID: mdl-38669509

RESUMEN

BACKGROUND: In Italy, cultural and professional nursing improvements are reached thanks to the university-based education which marks the clinical competency and the professional autonomy in nursing decision-making. OBJECTIVE: To highlight how Italian nurses perceived their nursing autonomy level in the main action-points highlighted in the Italian regulation law according to sex, age, work experience, education, shift and ward. METHODS: A cohort explorative study was carried out from September 2022 to January 2023 to highlight how Italian nurses perceived their nursing autonomy levels in the main action-points highlighted in the Italian regulation law for the nursing profession according to demographic characteristics, like: gender, age, work of experience, education, shift, ward employment. RESULTS: A total of 403 nurses were enrolled. Significant differences were recorded in: decision-making authority in patient care and shift (p≤0.001) and ward employment (p = 0.045); ability to initiate nursing interventions and education (p < 0.001) and ward employment (p = 0.011); collaboration and communication with healthcare team members and education (p < 0.001) and ward employment (p = 0.010); independence in clinical judgment and critical thinking and shift (p < 0.001); responsibility for the planning and evaluation of nursing care and education (p = 0.005) and shift (p = 0.002) and ward employment (p = 0.013); autonomy in professional development and continuing education and shift (p < 0.001) and ward employment (p < 0.001). CONCLUSIONS: The results highlighted the intricate world both of the healthcare surrounding and the abilities to act autonomously within the multiprofessional staff. Future studies will develop qualitative and phenomenological designs in order to better define in which fields nurses will act their professional autonomy.

17.
Int J Mol Sci ; 25(8)2024 Apr 13.
Artículo en Inglés | MEDLINE | ID: mdl-38673893

RESUMEN

During embryogenesis, basic fibroblast growth factor (bFGF) is released from neural tube and myotome to promote myogenic fate in the somite, and is routinely used for the culture of adult skeletal muscle (SKM) stem cells (MuSC, called satellite cells). However, the mechanism employed by bFGF to promote SKM lineage and MuSC proliferation has not been analyzed in detail. Furthermore, the question of if the post-translational modification (PTM) of bFGF is important to its stemness-promoting effect has not been answered. In this study, GST-bFGF was expressed and purified from E.coli, which lacks the PTM system in eukaryotes. We found that both GST-bFGF and commercially available bFGF activated the Akt-Erk pathway and had strong cell proliferation effect on C2C12 myoblasts and MuSC. GST-bFGF reversibly compromised the myogenesis of C2C12 myoblasts and MuSC, and it increased the expression of Myf5, Pax3/7, and Cyclin D1 but strongly repressed that of MyoD, suggesting the maintenance of myogenic stemness amid repressed MyoD expression. The proliferation effect of GST-bFGF was conserved in C2C12 over-expressed with MyoD (C2C12-tTA-MyoD), implying its independence of the down-regulation of MyoD. In addition, the repressive effect of GST-bFGF on myogenic differentiation was almost totally rescued by the over-expression of MyoD. Together, these evidences suggest that (1) GST-bFGF and bFGF have similar effects on myogenic cell proliferation and differentiation, and (2) GST-bFGF can promote MuSC stemness and proliferation by differentially regulating MRFs and Pax3/7, (3) MyoD repression by GST-bFGF is reversible and independent of the proliferation effect, and (4) GST-bFGF can be a good substitute for bFGF in sustaining MuSC stemness and proliferation.


Asunto(s)
Proliferación Celular , Factor 2 de Crecimiento de Fibroblastos , Desarrollo de Músculos , Proteína MioD , Mioblastos , Desarrollo de Músculos/genética , Animales , Ratones , Proteína MioD/metabolismo , Proteína MioD/genética , Factor 2 de Crecimiento de Fibroblastos/metabolismo , Factor 2 de Crecimiento de Fibroblastos/farmacología , Factor 2 de Crecimiento de Fibroblastos/genética , Mioblastos/metabolismo , Mioblastos/citología , Línea Celular , Factor de Transcripción PAX7/metabolismo , Factor de Transcripción PAX7/genética , Factor de Transcripción PAX3/metabolismo , Factor de Transcripción PAX3/genética , Factor 5 Regulador Miogénico/metabolismo , Factor 5 Regulador Miogénico/genética , Ciclina D1/metabolismo , Ciclina D1/genética , Células Satélite del Músculo Esquelético/metabolismo , Células Satélite del Músculo Esquelético/citología , Diferenciación Celular , Proteínas Proto-Oncogénicas c-akt/metabolismo , Músculo Esquelético/metabolismo , Músculo Esquelético/citología
18.
Bioorg Chem ; 147: 107400, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38688196

RESUMEN

Although certain members of the Ubiquitin-specific peptidases (USPs) have been recognized as promising therapeutic targets for various diseases, research progress regarding USP21 has been relatively sluggish in its early stages. USP21 is a crucial member of the USPs subfamily, involved in diverse cellular processes such as apoptosis, DNA repair, and signal transduction. Research findings from the past decade demonstrate that USP21 mediates the deubiquitination of multiple well-known target proteins associated with critical cellular processes relevant to both disease and homeostasis, particularly in various cancers.This reviewcomprehensively summarizes the structure and biological functions of USP21 with an emphasis on its role in tumorigenesis, and elucidates the advances on the discovery of tens of small-molecule inhibitors targeting USP21, which suggests that targeting USP21 may represent a potential strategy for cancer therapy.


Asunto(s)
Neoplasias , Ubiquitina Tiolesterasa , Humanos , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/metabolismo , Ubiquitina Tiolesterasa/antagonistas & inhibidores , Ubiquitina Tiolesterasa/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Animales , Inhibidores Enzimáticos/farmacología , Inhibidores Enzimáticos/química , Estructura Molecular
19.
Diagnostics (Basel) ; 14(7)2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38611671

RESUMEN

(1) Background: Transsphenoidal pituitary surgery can be conducted via microscopic or endoscopic approaches, and there has been a growing preference for the latter in recent years. However, the occurrence of rare complications such as postoperative sinusitis remains inadequately documented in the existing literature. (2) Methods: To address this gap, we conducted a comprehensive retrospective analysis of medical records spanning from 2018 to 2023, focusing on patients who underwent transsphenoidal surgery for pituitary neuroendocrine tumors (formerly called pituitary adenoma). Our study encompassed detailed evaluations of pituitary function and MRI imaging pre- and postsurgery, supplemented by transnasal endoscopic follow-up assessments at the otolaryngology outpatient department. Risk factors for sinusitis were compared using univariate and multivariate logistic regression analyses. (3) Results: Out of the 203 patients included in our analysis, a subset of 17 individuals developed isolated sphenoid sinusitis within three months postoperation. Further scrutiny of the data revealed significant associations between certain factors and the occurrence of postoperative sphenoid sinusitis. Specifically, the classification of the primary tumor emerged as a notable risk factor, with patients exhibiting nonfunctioning pituitary neuroendocrine tumors with 3.71 times the odds of developing sinusitis compared to other tumor types. Additionally, postoperative cortisol levels demonstrated a significant inverse relationship, with lower cortisol levels correlating with an increased risk of sphenoid sinusitis postsurgery. (4) Conclusions: In conclusion, our findings underscore the importance of considering tumor classification and postoperative cortisol levels as potential predictors of postoperative sinusitis in patients undergoing transsphenoidal endoscopic pituitary surgery. These insights offer valuable guidance for clinicians in identifying at-risk individuals and implementing tailored preventive and management strategies to mitigate the occurrence and impact of sinusitis complications in this patient population.

20.
J Korean Med Sci ; 39(15): e139, 2024 Apr 22.
Artículo en Inglés | MEDLINE | ID: mdl-38651224

RESUMEN

BACKGROUND: Post-hemorrhagic hydrocephalus (PHH), a common complication of severe intraventricular hemorrhage (IVH) in very low birth weight (BW) infants, is associated with significant morbidity and poor neurological outcomes. The objective of this study was to assess the current status of PHH and analyze the risk factors associated with the necessity of treatment for PHH in infants born between 22 and 28 weeks of gestation, specifically those with severe IVH (grade 3 or 4). METHODS: The analysis was conducted on 1,097 infants who were born between 22-28 gestational weeks and diagnosed with severe IVH, using data from the Korean Neonatal Network. We observed that the prevalence of PHH requiring treatment was 46.3% in infants with severe IVH. RESULTS: Higher rates of mortality, transfer during admission, cerebral palsy, and ventriculoperitoneal shunt after discharge were higher in infants with PHH than in those without PHH. PHH in severe IVH was associated with a higher rate of pulmonary hemorrhage, seizures, and IVH grade 4 in the entire cohort. In addition, it was associated with a lower rate of small for gestational age and chorioamnionitis. In the subgroup analysis, high BW, outborn status, pulmonary hemorrhage, seizure, sepsis, and IVH grade 4 were associated with a higher incidence of PHH between 22 and 25 gestational weeks (GW). In infants born between 26 and 28 GW, a higher incidence of PHH was associated with seizures and IVH grade 4. CONCLUSION: It is necessary to maintain meticulous monitoring and neurological intervention for infants with PHH not only during admission but also after discharge. In addition, identifying the clinical factors that increase the likelihood of developing PHH from severe IVH is crucial.


Asunto(s)
Edad Gestacional , Hidrocefalia , Humanos , Hidrocefalia/complicaciones , República de Corea/epidemiología , Recién Nacido , Femenino , Masculino , Factores de Riesgo , Estudios de Cohortes , Hemorragia Cerebral/complicaciones , Índice de Severidad de la Enfermedad , Hemorragia Cerebral Intraventricular/complicaciones , Derivación Ventriculoperitoneal , Lactante , Recién Nacido de muy Bajo Peso
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