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1.
Int J Mol Sci ; 25(13)2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-39000397

RESUMO

Prostate adenocarcinoma (PRAD) is the second most common tumor associated with death. The role and mechanisms of the fragile X mental retardation 1 (FMR1) gene in PRAD remain unknown. We conducted an analysis of FMR1 expression in PRAD to determine its prognostic importance and connection to carcinogenic pathways such as PI3K_AKT_mTOR. Survival analyses were utilized to establish a correlation between FMR1 expression and patient outcomes. We used the integration of genomic data with bioinformatic predictions to predict the regulatory factors of the FMR1 gene in PRAD. Our data revealed that individuals with higher levels of FMR1 expression experience worse survival outcomes compared to those with lower expression (hazard ratio [HR] = 5.08, 95% confidence interval [CI] = 1.07 - 24, p = 0.0412). FMR1 expression was significantly higher in patients with advanced pathological tumor stages, particularly in the pT3 and pT4 combined stages and the pN1 nodal stage. Furthermore, patients with high Gleason scores (GSs) (combined GSs 8 and 9) exhibited increased levels of FMR1 expression. Our results further identify a possible regulatory link between FMR1 and key oncogenic pathways, including PI3K_AKT_mTOR, and predict the possible mechanism by which FMR1 is regulated in PRAD. Our data suggest that the FMR1 gene could serve as a biomarker for PRAD progression. However, in-depth investigations, including those with large patient samples and in vitro studies, are needed to validate this finding and understand the mechanisms involved.


Assuntos
Adenocarcinoma , Proteína do X Frágil da Deficiência Intelectual , Regulação Neoplásica da Expressão Gênica , Neoplasias da Próstata , Humanos , Proteína do X Frágil da Deficiência Intelectual/genética , Proteína do X Frágil da Deficiência Intelectual/metabolismo , Masculino , Neoplasias da Próstata/genética , Neoplasias da Próstata/metabolismo , Neoplasias da Próstata/patologia , Neoplasias da Próstata/mortalidade , Prognóstico , Adenocarcinoma/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patologia , Adenocarcinoma/mortalidade , Idoso , Pessoa de Meia-Idade , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Serina-Treonina Quinases TOR/metabolismo , Serina-Treonina Quinases TOR/genética , Transdução de Sinais/genética , Fosfatidilinositol 3-Quinases/metabolismo , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo , Proteínas Proto-Oncogênicas c-akt/genética
2.
Cureus ; 15(7): e42538, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-37637519

RESUMO

Autoimmune enteropathy (AIE) is a differential diagnosis of incurable chronic diarrhea, malnutrition, and weight loss. This type of diarrhea is associated with protein enteropathy that usually affects the small intestine. The diagnosis of AIE is based on chronic diarrhea, malabsorption, specific histological result, antibodies against enterocytes, and excluding similar conditions. In this case, a 28-year-old female presented with diarrhea, lower limb edema, weight loss, and electrolyte imbalances. Endoscopic examination demonstrated duodenal villous atrophy, while duodenal biopsies revealed villous blunting, scattered intraepithelial lymphocytes, and crypt hyperplasia in the lamina propria. The patient was treated with immunosuppressive treatment including methylprednisolone and azathioprine, achieving clinical remission.

3.
Acta Crystallogr E Crystallogr Commun ; 77(Pt 8): 834-838, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34422311

RESUMO

The title compound {systematic name: (S,E)-3-[4-(furan-2-yl)-2,3,4,5-tetra-hydro-1H-benzo[b][1,4]diazepin-2-yl-idene]-6-methyl-2H-pyran-2,4(3H)-dione}, C19H16N2O4, is constructed from a benzodiazepine ring system linked to furan and pendant di-hydro-pyran rings, where the benzene and furan rings are oriented at a dihedral angle of 48.7 (2)°. The pyran ring is modestly non-planar [largest deviation of 0.029 (4) Šfrom the least-squares plane] while the tetra-hydro-diazepine ring adopts a boat conformation. The rotational orientation of the pendant di-hydro-pyran ring is partially determined by an intra-molecular N-HDiazp⋯ODhydp (Diazp = diazepine and Dhydp = di-hydro-pyran) hydrogen bond. In the crystal, layers of mol-ecules parallel to the bc plane are formed by N-HDiazp⋯ODhydp hydrogen bonds and slipped π-π stacking inter-actions. The layers are connected by additional slipped π-π stacking inter-actions. A Hirshfeld surface analysis of the crystal structure indicates that the most important contributions for the crystal packing are from H⋯H (46.8%), H⋯O/O⋯H (23.5%) and H⋯C/C⋯H (15.8%) inter-actions, indicating that van der Waals inter-actions are the dominant forces in the crystal packing. Computational chemistry indicates that in the crystal the N-H⋯O hydrogen-bond energy is 57.5 kJ mol-1.

4.
Acta Crystallogr E Crystallogr Commun ; 77(Pt 5): 559-563, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-34026265

RESUMO

The title mol-ecule, C17H26N2O, adopts an L-shaped conformation, with the straight n-decyl chain positioned nearly perpendicular to the di-hydro-benzimidazole moiety. The di-hydro-benzimidazole portion is not quite planar as there is a dihedral angle of 1.20 (6)° between the constituent planes. In the crystal, N-H⋯O hydrogen bonds form inversion dimers, which are connected into the three-dimensional structure by C-H⋯O hydrogen bonds and C-H⋯π(ring) inter-actions. Hirshfeld surface analysis indicates that the most important contributions for the crystal packing are from H⋯H (75.9%), H⋯C/C⋯H (12.5%) and H⋯O/O⋯H (7.0%) inter-actions. Based on computational chemistry using the CE-B3LYP/6-31 G(d,p) energy model, C-H⋯O hydrogen bond energies are -74.9 (for N-H⋯O) and -42.7 (for C-H⋯O) kJ mol-1.

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