Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 159
Filtrar
1.
Semin Dial ; 2024 Sep 04.
Artículo en Inglés | MEDLINE | ID: mdl-39229958

RESUMEN

BACKGROUND: Tidal peritoneal dialysis (TPD) provides better fluid flow mechanics and is more comfortable for the patient, owing to fewer alarms and less pain during inflow and outflow. The long-term characteristics of patients with TPD were not evident. In this randomized controlled follow-up study, we aimed to explore the characteristics of patients with TPD, compared to IPD. METHODS: A total of 85 patients were randomized to either IPD or 70% TPD between January 2019 and December 2020, and all patients were followed up on December 2021. The characteristics of patients between the two groups were analyzed using a t-test or chi-square as appropriate. The overall survival and technical survival were analyzed using Kaplan-Meier analysis. RESULTS: Forty-two patients were assigned to IPD, and 43 patients were assigned to TPD. The basal characteristics of patients were not different between the two groups. In an average of 16 months of follow-up, 19 patients died, and 25 patients dropped out of peritoneal dialysis. The two groups had no difference in overall survival and technical survival. TPD was associated with high urine volume (p = 0.001), lower blood urea nitrogen (p = 0.002), lower phosphorus (p = 0.004), and fewer cycler alarms (p < 0.001). The chance of patients reporting abdominal fullness was higher in patients with TPD (p = 0.001). CONCLUSION: In the randomized, controlled, follow-up study, TPD may preserve residual renal function and is associated with lower urea nitrogen and phosphorus in chronic peritoneal dialysis patients. TPD is associated with fewer cycler alarms but may increase the chance of patients reporting abdominal distension.

2.
J Med Life ; 17(6): 588-592, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-39296444

RESUMEN

Individual personality refers to the Ego and the interpersonal sector. The Ego corresponds to consciousness and self-esteem, including the capacities for emotional self-regulation, self-control, self-evaluation, and self-direction in relation to personal goals. When neoplastic and psychiatric diseases coexist, a patient's quality of life is significantly impacted. While there are somatic differences in disease progression, how the illness is perceived and mainly experienced depends on personality traits. In this study, we administered the DECAS Personality Inventory (a Romanian-validated instrument based on the Five-Factor model of personality) to a group of 121 patients diagnosed with breast cancer to explore the relationships among their personality traits. Descriptive statistics revealed that the mean T scores for openness, extroversion, and emotional stability were low, while the scores for conscientiousness and agreeableness were at an average level. Our findings suggest that, in the studied group, low levels of emotional stability, extroversion, and openness were unfavorable personality dimensions that should be a primary focus of therapeutic strategies, as they significantly affect the quality of life in patients with breast cancer.


Asunto(s)
Neoplasias de la Mama , Personalidad , Calidad de Vida , Humanos , Neoplasias de la Mama/psicología , Neoplasias de la Mama/patología , Femenino , Estudios Transversales , Persona de Mediana Edad , Adulto , Rumanía , Inventario de Personalidad , Anciano
3.
Alzheimers Res Ther ; 16(1): 204, 2024 Sep 16.
Artículo en Inglés | MEDLINE | ID: mdl-39285454

RESUMEN

BACKGROUND: The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer's disease (EOAD). Yet, detailed examination of MTL subfields and drivers of atrophy in amnestic EOAD is lacking. METHODS: BioFINDER-2 participants with memory impairment, abnormal amyloid-ß and tau-PET were included. Forty-one amnestic EOAD individuals ≤65 years and, as comparison, late-onset AD (aLOAD, ≥70 years, n = 154) and amyloid-ß-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured. RESULTS: AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups: aLOAD showed thinner entorhinal cortices than aEOAD; aEOAD showed thinner parietal regions than aLOAD. aEOAD showed lower white matter hyperintensities than aLOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity were found. CONCLUSIONS: We found evidence for MTL atrophy in amnestic EOAD and overall similar levels to aLOAD of MTL tau pathology and co-pathologies.


Asunto(s)
Enfermedad de Alzheimer , Atrofia , Tomografía de Emisión de Positrones , Lóbulo Temporal , Humanos , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Atrofia/patología , Masculino , Femenino , Anciano , Lóbulo Temporal/patología , Lóbulo Temporal/diagnóstico por imagen , Persona de Mediana Edad , Imagen por Resonancia Magnética , Proteínas tau/metabolismo , Edad de Inicio , Péptidos beta-Amiloides/metabolismo , Amnesia/patología , Amnesia/diagnóstico por imagen , Anciano de 80 o más Años
4.
Drug Discov Today ; 29(10): 104155, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39214495

RESUMEN

Eukaryotic elongation factor 2 kinase (eEF2K) is a member of the α-kinase family that is activated by calcium/calmodulin. Of note, eEF2K is crucial for regulating translation and is often highly overexpressed in malignant cells. Therefore in this review, we summarize the molecular structure of eEF2K and its oncogenic roles in cancer. Moreover, we further discuss the inhibition of eEF2K with small-molecule inhibitors and other new emerging therapeutic strategies in cancer therapy. Taken together, these inspiring findings provide new insights into a promising strategy for inhibiting eEF2K to greatly improve future cancer therapy.


Asunto(s)
Antineoplásicos , Quinasa del Factor 2 de Elongación , Neoplasias , Inhibidores de Proteínas Quinasas , Humanos , Quinasa del Factor 2 de Elongación/antagonistas & inhibidores , Quinasa del Factor 2 de Elongación/metabolismo , Neoplasias/tratamiento farmacológico , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Antineoplásicos/química , Inhibidores de Proteínas Quinasas/farmacología , Inhibidores de Proteínas Quinasas/uso terapéutico , Inhibidores de Proteínas Quinasas/química , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/química , Terapia Molecular Dirigida
5.
ChemMedChem ; : e202400326, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38993102

RESUMEN

Proteolysis-targeting chimeras (PROTACs) have emerged as a promising technology for inducing targeted protein degradation by leveraging the intrinsic ubiquitin-proteasome system (UPS). While the potential druggability of PROTACs toward undruggable proteins has accelerated their rapid development and the wide-range of applications across diverse disease contexts, off-tissue effect and side-effects of PROTACs have recently received attentions to improve their efficacy. To address these issues, spatial or temporal target protein degradation by PROTACs has been spotlighted. In this review, we explore chemical strategies for modulating protein degradation in a cell type-specific (spatio-) and time-specific (temporal-) manner, thereby offering insights for expanding PROTAC applications to overcome the current limitations of target protein degradation strategy.

6.
Eval Program Plann ; 106: 102467, 2024 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-39059177

RESUMEN

Professional Development (PD) programs in Pakistan typically follow a standardized approach, often overlooking the diverse strengths and weaknesses of various teacher groups, which may not adequately address their specific needs. This study aims to evaluate teacher competencies among different groups from the perspective of school principals in Pakistan's public schools, with the goal of enhancing the effectiveness of PD programs. Initially, the study identifies three key themes of 21st-century teacher competencies through an extensive review of recent literature. An interview guide, based on these competencies, was used to gather data from seven public school principals via structured interviews. The data were analyzed using a deductive content analysis approach, with MAXQDA software employed for theme coding. The findings revealed notable differences in teacher competencies from the principals' perspectives. Female and younger teachers exhibited more competencies compared to their male and senior counterparts. These insights provide crucial information for planning and customizing Teacher Professional Development (TPD) programs, emphasizing an objective evaluation of teachers rather than self-assessment. Tailored PD programs based on these findings can more effectively enhance teachers' professional growth and competence."


Asunto(s)
Competencia Profesional , Evaluación de Programas y Proyectos de Salud , Maestros , Instituciones Académicas , Humanos , Pakistán , Competencia Profesional/normas , Femenino , Masculino , Instituciones Académicas/organización & administración , Instituciones Académicas/normas , Desarrollo de Personal/organización & administración , Factores Sexuales , Adulto , Formación del Profesorado/normas , Factores de Edad , Entrevistas como Asunto
7.
Biomed Pharmacother ; 178: 117218, 2024 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-39084081

RESUMEN

Histone deacetylase 6 (HDAC6) plays a crucial role in the initiation and progression of various cancers, as its overexpression is linked to tumor growth, invasion, migration, survival, apoptosis, and angiogenesis. Therefore, HDAC6 has emerged as an attractive target for anticancer drug discovery in the past decade. However, the development of conventional HDAC6 inhibitors has been hampered by their limited clinical efficacy, acquired resistance, and inability to inhibit non-enzymatic functions of HDAC6. To overcome these challenges, new strategies, such as dual-acting inhibitors, targeted protein degradation (TPD) technologies (including PROTACs, HyT), are essential to enhance the anticancer activity of HDAC6 inhibitors. In this review, we focus on the recent advances in the design and development of HDAC6 modulators, including isoform-selective HDAC6 inhibitors, HDAC6-based dual-target inhibitors, and targeted protein degraders (PROTACs, HyT), from the perspectives of rational design, pharmacodynamics, pharmacokinetics, and clinical status. Finally, we discuss the challenges and future directions for HDAC6-based drug discovery for cancer therapy.


Asunto(s)
Antineoplásicos , Histona Desacetilasa 6 , Inhibidores de Histona Desacetilasas , Neoplasias , Humanos , Histona Desacetilasa 6/antagonistas & inhibidores , Histona Desacetilasa 6/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/enzimología , Inhibidores de Histona Desacetilasas/uso terapéutico , Inhibidores de Histona Desacetilasas/farmacología , Animales , Antineoplásicos/farmacología , Antineoplásicos/uso terapéutico , Terapia Molecular Dirigida , Bibliotecas de Moléculas Pequeñas/farmacología , Bibliotecas de Moléculas Pequeñas/uso terapéutico
9.
Cureus ; 16(5): e60559, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38887337

RESUMEN

A pancreatic pseudocyst (PPC) is a frequent complication of pancreatitis, often stemming from alcohol, gallstones, or hyperlipidemia. Endoscopic treatment of PPC has become the mainstream treatment. A case of one giant and multiple small PPCs was observed, manifesting as repeated abdominal bloating, abdominal pain, nausea, and vomiting after meals. Initial computed tomography scans revealed the presence of multiple PPCs. Despite ineffective medical treatment, the pseudocysts progressively increased. In response, we conducted a combined endoscopic intervention, involving Hot AXIOS (Boston Scientific, Marlborough, MA) stenting through endoscopic ultrasound-guided transmural drainage (EUS-TMD) and the placement of the endoscopic nasopancreatic drainage (ENPD) mimic stent through endoscopic retrograde pancreatography (ERP). Remarkably, after nine months of postoperative follow-up, the patient had no discomfort symptoms and the cyst disappeared. We conducted a literature review on endoscopic combined drainage for PPCs, which is still controversial. Our presented case serves as a demonstration that endoscopic combined drainage can effectively and successfully manage giant and multiple PPCs.

10.
Expert Opin Drug Discov ; 19(7): 799-813, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38825802

RESUMEN

INTRODUCTION: Hydrophobic tagging (HyT) technology presents a distinct therapeutic strategy diverging from conventional small molecule drugs, providing an innovative approach to drug design. This review aims to provide an overview of the HyT literature and future outlook to offer guidance for drug design. AREAS COVERED: In this review, the authors introduce the composition, mechanisms and advantages of HyT technology, as well as summarize the detailed applications of HyT technology in anti-cancer, neurodegenerative diseases (NDs), autoimmune disorders, cardiovascular diseases (CVDs), and other fields. Furthermore, this review discusses key aspects of the future development of HyT molecules. EXPERT OPINION: HyT emerges as a highly promising targeted protein degradation (TPD) strategy, following the successful development of proteolysis targeting chimeras (PROTAC) and molecular glue. Based on exploring new avenues, modification of the HyT molecule itself potentially enhances the technology. Improved synthetic pathways and emphasis on pharmacokinetic (PK) properties will facilitate the development of HyT. Furthermore, elucidating the biochemical basis by which the compound's hydrophobic moiety recruits the protein homeostasis network will enable the development of more precise assays that can guide the optimization of the linker and hydrophobic moiety.


Asunto(s)
Diseño de Fármacos , Desarrollo de Medicamentos , Interacciones Hidrofóbicas e Hidrofílicas , Bibliotecas de Moléculas Pequeñas , Humanos , Animales , Diseño de Fármacos/métodos , Bibliotecas de Moléculas Pequeñas/farmacología , Desarrollo de Medicamentos/métodos , Proteolisis
11.
Chin Clin Oncol ; 13(3): 33, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38859601

RESUMEN

BACKGROUND: Breast cancer (BRCA) represents a significant health challenge for women globally, with refractory cases showing resistance to current therapeutic strategies. The discovery of novel molecular markers and therapeutic targets is critical for improving outcomes in these patients. The primary aim of this study is to elucidate the role of tumor protein D52 (TPD52) as a novel molecular marker and potential therapeutic target to improve outcomes for BRCA patients. METHODS: Using bioinformatics methods, we screened and evaluated the expression, prognosis, and associated mechanisms of TPD52 in BRCA. Two hundred and thirty-eight BRCA cases and 19 control cases were collected from Shanghai First Maternity and Infant Hospital, and the protein expression of TPD52 was detected by immunohistochemistry, and the correlation between TPD52 and the prognosis of BRCA was analyzed. RESULTS: The expression of TPD52 in BRCA tissues was significantly higher than that in the control (P<0.001), displaying a strong association with key clinical variables, concurrently indicating an unfavorable prognostic implication. The survival analysis revealed high TPD52 expression was an independent adverse prognostic factor for overall (P=0.008) and disease-specific survival (P=0.005). Gene set enrichment analysis showed that TPD52 negatively correlated with estradiol, AMP-activated protein kinase, and other responses. Immune infiltration analysis showed that TPD52 was associated with immune cell infiltration, Th-1/Th-2 cell balance, and immune defense cells such as dendritic and plasmacytoid dendritic cells. It is further found that high TPD52 expression is associated with progression-free and disease-free survival from the analysis of immunohistochemical data of the patients at our hospital. CONCLUSIONS: In summary, TPD52 may serve as an independent prognostic biomarker for BRCA, which may represent a promising novel therapeutic target, particularly for the refractory estrogen receptor-positive (ER+)/progesterone receptor-positive (PR+)/human epidermal growth factor receptor 2-positive (HER2+) BRCA cases that have failed endocrine therapy and targeted treatment.


Asunto(s)
Biomarcadores de Tumor , Neoplasias de la Mama , Humanos , Femenino , Neoplasias de la Mama/patología , Pronóstico , Biomarcadores de Tumor/metabolismo , Persona de Mediana Edad , Proteínas de Neoplasias/metabolismo , Receptores de Estrógenos/metabolismo , Receptor ErbB-2/metabolismo , Adulto , Receptores de Progesterona/metabolismo
12.
bioRxiv ; 2024 May 21.
Artículo en Inglés | MEDLINE | ID: mdl-38826333

RESUMEN

Background: The medial temporal lobe (MTL) is hypothesized to be relatively spared in early-onset Alzheimer's disease (EOAD). Yet, detailed examination of MTL subfield volumes and drivers of atrophy in amnestic EOAD is lacking. Methods: BioFINDER-2 participants with memory impairment, abnormal amyloid-ß status and tau-PET were included. Forty-one EOAD individuals aged ≤65 years and, as comparison, late-onset AD (LOAD, ≥70 years, n=154) and Aß-negative cognitively unimpaired controls were included. MTL subregions and biomarkers of (co-)pathologies were measured. Results: AD groups showed smaller MTL subregions compared to controls. Atrophy patterns were similar across AD groups, although LOAD showed thinner entorhinal cortices compared to EOAD. EOAD showed lower WMH compared to LOAD. No differences in MTL tau-PET or transactive response DNA binding protein 43-proxy positivity was found. Conclusions: We found in vivo evidence for MTL atrophy in amnestic EOAD and overall similar levels to LOAD of MTL tau pathology and co-pathologies.

13.
Nanotechnology ; 35(36)2024 Jun 18.
Artículo en Inglés | MEDLINE | ID: mdl-38888294

RESUMEN

In this perspective we discuss the progress made in the mechanistic studies of the surface chemistry associated with the atomic layer deposition (ALD) of metal films and the usefulness of that knowledge for the optimization of existing film growth processes and for the design of new ones. Our focus is on the deposition of late transition metals. We start by introducing some of the main surface-sensitive techniques and approaches used in this research. We comment on the general nature of the metallorganic complexes used as precursors for these depositions, and the uniqueness that solid surfaces and the absence of liquid solvents bring to the ALD chemistry and differentiate it from what is known from metalorganic chemistry in solution. We then delve into the adsorption and thermal chemistry of those precursors, highlighting the complex and stepwise nature of the decomposition of the organic ligands that usually ensued upon their thermal activation. We discuss the criteria relevant for the selection of co-reactants to be used on the second half of the ALD cycle, with emphasis on the redox chemistry often associated with the growth of metallic films starting from complexes with metal cations. Additional considerations include the nature of the substrate and the final structural and chemical properties of the growing films, which we indicate rarely retain the homogeneous 2D structure often aimed for. We end with some general conclusions and personal thoughts about the future of this field.

14.
Expert Opin Ther Pat ; 34(4): 211-229, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-38742308

RESUMEN

INTRODUCTION: SMARCA2 and SMARCA4 are subunits of the SWI/SNF complex which is a chromatin remodeling complex and a key epigenetic regulator that facilitates gene expression. Tumors with loss of function mutations in SMARCA4 rely on SMARCA2 for cell survival and this synthetic lethality is a potential therapeutic strategy to treat cancer. AREAS COVERED: The current review focuses on patent applications that claim proteolysis-targeting chimeras (PROTAC) degraders that bind the bromodomain site of SMARCA2 and are published between January 2019-June 2023. A total of 29 applications from 9 different applicants were evaluated. EXPERT OPINION: SMARCA2/4 bromodomain inhibitors do not lead to desired effects on cancer proliferation; however, companies have converted bromodomain binders into PROTACs to degrade the protein, with a preference for SMARCA2 over SMARCA4. Selective degradation of SMARCA2 is most likely required to be efficacious in the SMARCA4-deficient setting, while allowing for sufficient safety margin in normal tissues. With several patent applications disclosed recently, interest in targeting SMARCA2 should continue, especially with a selective SMARCA2 PROTAC now in the clinic from Prelude Therapeutics. The outcome of the clinical trials will influence the evolution of selective SMARCA2 PROTACs development.


Asunto(s)
Antineoplásicos , ADN Helicasas , Neoplasias , Proteínas Nucleares , Patentes como Asunto , Mutaciones Letales Sintéticas , Factores de Transcripción , Humanos , Factores de Transcripción/metabolismo , Neoplasias/tratamiento farmacológico , Neoplasias/patología , Neoplasias/genética , Neoplasias/metabolismo , Proteínas Nucleares/metabolismo , Proteínas Nucleares/antagonistas & inhibidores , Animales , ADN Helicasas/metabolismo , Antineoplásicos/farmacología , Proteolisis/efectos de los fármacos , Histona Acetiltransferasas/metabolismo , Histona Acetiltransferasas/antagonistas & inhibidores , Terapia Molecular Dirigida
15.
Cell Chem Biol ; 31(7): 1290-1304.e7, 2024 Jul 18.
Artículo en Inglés | MEDLINE | ID: mdl-38657608

RESUMEN

Proteolysis-targeting chimeras (PROTACs) are heterobifunctional molecules consisting of two ligands joined by a linker, enabling them to simultaneously bind with an E3 ligase and a protein of interest (POI) and trigger proteasomal degradation of the POI. Limitations of PROTAC include lack of potent E3 ligands, poor cell selectivity, and low permeability. AS1411 is an antitumor aptamer specifically recognizing a membrane-nucleus shuttling nucleolin (NCL). Here, we repurpose AS1411 as a ligand for an E3 ligase mouse double minute 2 homolog (MDM2) via anchoring the NCL-MDM2 complex. Then, we construct an AS1411-NCL-MDM2-based PROTAC (ANM-PROTAC) by conjugating AS1411 with large-molecular-weight ligands for "undruggable" oncogenic STAT3, c-Myc, p53-R175H, and AR-V7. We show that the ANM-PROTAC efficiently penetrates tumor cells, recruits MDM2 and degrades the POIs. The ANM-PROTAC achieves tumor-selective distribution and exhibits excellent antitumor activity with no systemic toxicity. This is a PROTAC with built-in tumor-targeting and cell-penetrating capacities.


Asunto(s)
Antineoplásicos , Aptámeros de Nucleótidos , Proteolisis , Proteínas Proto-Oncogénicas c-mdm2 , Humanos , Proteínas Proto-Oncogénicas c-mdm2/metabolismo , Proteínas Proto-Oncogénicas c-mdm2/antagonistas & inhibidores , Animales , Ratones , Proteolisis/efectos de los fármacos , Aptámeros de Nucleótidos/química , Aptámeros de Nucleótidos/farmacología , Aptámeros de Nucleótidos/metabolismo , Antineoplásicos/farmacología , Antineoplásicos/química , Antineoplásicos/síntesis química , Ligandos , Nucleolina , Proteínas de Unión al ARN/metabolismo , Reposicionamiento de Medicamentos , Femenino , Ratones Desnudos , Proliferación Celular/efectos de los fármacos , Línea Celular Tumoral , Ratones Endogámicos BALB C , Fosfoproteínas/metabolismo , Fosfoproteínas/antagonistas & inhibidores , Fosfoproteínas/química , Ensayos de Selección de Medicamentos Antitumorales , Quimera Dirigida a la Proteólisis , Oligodesoxirribonucleótidos
16.
Cells ; 13(7)2024 Mar 26.
Artículo en Inglés | MEDLINE | ID: mdl-38607017

RESUMEN

Proteolysis-targeting chimeras (PROTACs) describe compounds that bind to and induce degradation of a target by simultaneously binding to a ubiquitin ligase. More generally referred to as bifunctional degraders, PROTACs have led the way in the field of targeted protein degradation (TPD), with several compounds currently undergoing clinical testing. Alongside bifunctional degraders, single-moiety compounds, or molecular glue degraders (MGDs), are increasingly being considered as a viable approach for development of therapeutics, driven by advances in rational discovery approaches. This review focuses on drug discovery with respect to bifunctional and molecular glue degraders within the ubiquitin proteasome system, including analysis of mechanistic concepts and discovery approaches, with an overview of current clinical and pre-clinical degrader status in oncology, neurodegenerative and inflammatory disease.


Asunto(s)
Descubrimiento de Drogas , Oncología Médica , Citoplasma , Complejo de la Endopetidasa Proteasomal , Proteolisis , Ubiquitina
17.
J Clin Med ; 13(7)2024 Apr 02.
Artículo en Inglés | MEDLINE | ID: mdl-38610817

RESUMEN

Objectives: The study aims to assess and classify complications in patients treated for maxillary transverse deficiency using surgically assisted rapid maxillary/palatal expansion (SARME/SARPE) under general anesthesia. The classification of the complications aimed to assess the difficulty of their treatment as well as estimate its real cost. Methods: The retrospective study covered 185 patients who underwent surgery for a skeletal deformity in the form of maxillary constriction or in which maxillary constriction was one of its components treated by a team of maxillofacial surgeons at one center (97 females and 88 males, aged 15 to 47 years, mean age 26.1 years). Complications were divided into two groups: early complications (up to 3 weeks after surgery) and late complications (>3 weeks after surgery). In relation to the occurrence of complications, we analyzed the demographic characteristics of the group, type of skeletal deformity (class I, II, III), presence of open bite and asymmetry, surgical technique, type and size of appliance used for maxillary expansion, as well as the duration of surgery. Results: In the study group, complications were found in 18 patients (9.73%). Early complications were found in nine patients, while late complications were also found in nine patients. Early complications include no possibility of distraction, palatal mucosa necrosis, perforation of the maxillary alveolar process caused by the distractor and asymmetric distraction. Late complications include maxillary incisor root resorption, no bone formation in the distraction gap, and maxillary incisor necrosis. None of the patients required prolonged hospitalization and only one required reoperation. Conclusions: Complications were found in 18 patients (9.73%). All challenges were classified as minor difficulties since they did not suppress the final outcome of the treatment of skeletal malocclusion. However, the complications that did occur required additional corrective measures. Surgically assisted rapid maxillary expansion, when performed properly and in correlation with the correct orthodontic treatment protocol, is an effective and predictable technique for treating maxillary constriction.

18.
Front Mol Neurosci ; 17: 1370509, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38685916

RESUMEN

Targeted protein degradation (TPD) is a rapidly expanding field, with various PROTACs (proteolysis-targeting chimeras) in clinical trials and molecular glues such as immunomodulatory imide drugs (IMiDs) already well established in the treatment of certain blood cancers. Many current approaches are focused on oncology targets, leaving numerous potential applications underexplored. Targeting proteins for degradation offers a novel therapeutic route for targets whose inhibition remains challenging, such as protein aggregates in neurodegenerative diseases. This mini review focuses on the prospect of utilizing TPD for neurodegenerative disease targets, particularly PROTAC and molecular glue formats and opportunities for novel CNS E3 ligases. Some key challenges of utilizing such modalities including molecular design of degrader molecules, drug delivery and blood brain barrier penetrance will be discussed.

19.
Eur J Med Chem ; 269: 116270, 2024 Apr 05.
Artículo en Inglés | MEDLINE | ID: mdl-38490062

RESUMEN

Kelch-like proteins (KLHLs) are a large family of BTB-containing proteins. KLHLs function as the substrate adaptor of Cullin 3-RING ligases (CRL3) to recognize substrates. KLHLs play pivotal roles in regulating various physiological and pathological processes by modulating the ubiquitination of their respective substrates. Mounting evidence indicates that mutations or abnormal expression of KLHLs are associated with various human diseases. Targeting KLHLs is a viable strategy for deciphering the KLHLs-related pathways and devising therapies for associated diseases. Here, we comprehensively review the known KLHLs inhibitors to date and the brilliant ideas underlying their development.


Asunto(s)
Proteínas Cullin , Ubiquitina-Proteína Ligasas , Humanos , Proteínas Cullin/metabolismo , Ubiquitinación , Ubiquitina-Proteína Ligasas/metabolismo
20.
Polymers (Basel) ; 16(5)2024 Feb 20.
Artículo en Inglés | MEDLINE | ID: mdl-38475254

RESUMEN

Polymer composites based on poly(N,N'-bis-4-butylphenyl-N,N'-bisphenyl)benzidine (poly-TPD) with PCBM and copper(II) pyropheophorbide derivative (Cu-PP) were developed. In thin films of the poly-TPD and Cu-PP composites, the charge carrier mobility was investigated for the first time. In the ternary poly-TPD:PCBM:Cu-PP composite, the electron and hole mobilities are the most balanced compared to binary composites and the photoconductivity is enhanced due to the sensitization by Cu-PP in blue and red spectral ranges. The new composites are promising for use in the development of photodetectors.

SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA