A series of 1, 2, 4-triazole derivatives bearing piperidine moiety has been introduced as new anti-diabetic drug candidates with least cytotoxicity. p-Chlorophenylsulfonyl chloride (1) and ethyl nipecotate (2) were the starting reagents that resulted into corresponding 3,4,5-trisubstituted-1,2,4-triazole (6) through a series of steps. A series of electrophiles, 9a-e, were synthesized by reacting 4-bromobutyryl chloride (7) with differently substituted aromatic amines (8a-e) under basic aqueous medium. Target derivatives, 10a-e, were synthesized by the reaction of compound 6 with N-aryl-4-bromobutanamides (9a-e) in an aprotic solvent. Structures of all the derivatives were verified by spectroscopic analysis using IR, H-NMR, C-NMR and EIMS. Most of the derivatives revealed moderate to good α-glucosidase inhibitory activity with reference to acarbose. The moderate hemolytic potential demonstrated least toxicity.
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J Clin Invest
January 2025
Eppley Institute for Research in Cancer and Allied Diseases, University of Nebraska Medical Center, Omaha, United States of America.
Dysregulated eIF4E-dependent translation is a central driver of tumorigenesis and therapy resistance. eIF4E binding proteins (4E-BP1/2/3) are major negative regulators of eIF4E-dependent translation that are inactivated in tumors through inhibitory phosphorylation or downregulation. Previous studies have linked PP2A phosphatase(s) to activation of 4E-BP1.
View Article and Find Full Text PDFAnesthesiology
January 2025
Key Laboratory of Brain Science, Key Laboratory of Anesthesia and Organ Protection of Ministry of Education (In Cultivation), Zunyi Medical University, Zunyi, 563100, Guizhou Province, China.
Background: The medial prefrontal cortex plays a crucial role in regulating consciousness. However, the specific functions of its excitatory and inhibitory networks during anesthesia remain uncertain. Here we explored the hypothesis that somatostatin interneurons in the medial prefrontal cortex enhance the effects of sevoflurane anesthesia by increasing GABA transmission to pyramidal neurons.
View Article and Find Full Text PDFPLoS One
January 2025
Departamento de Psicología Evolutiva y Comunicación, Campus Universitario de Vigo, University of Vigo, Vigo, Spain.
The main purpose of this study was to examine the age-related changes in inhibitory control of 450 children at the ages of 7-8, 11-12, and 14-16 when controlling for working memory capacity (WMC) and processing speed to determine whether inhibition is an independent factor far beyond its possible reliance on the other two factors. This examination is important for several reasons. First, empirical evidence about age-related changes of inhibitory control is controversial.
View Article and Find Full Text PDFPLoS One
January 2025
Division of Oral Physiology, Faculty of Dentistry, Niigata University Graduate School of Medical and Dental Sciences, Niigata, Japan.
This study examined the effects of treadmill running (TR) regimens on craniofacial pain- and anxiety-like behaviors, as well as their effects on neural changes in specific brain regions of male mice subjected to repeated social defeat stress (SDS) for 10 days. Behavioral and immunohistochemical experiments were conducted to evaluate the impact of TR regimens on SDS-related those behaviors, as well as epigenetic and neural activity markers in the anterior cingulate cortex (ACC), insular cortex (IC), rostral ventromedial medulla (RVM), and cervical spinal dorsal horn (C2). Behavioral responses were quantified using multiple tests, while immunohistochemistry measured histone H3 acetylation, histone deacetylases (HDAC1, HDAC2), and neural activity markers (FosB and phosphorylated cAMP response element-binding protein (pCREB).
View Article and Find Full Text PDFPLoS One
January 2025
Department of Anatomy, University Hospital Essen, Essen, Germany.
Prostate cancer is the second most common type of cancer in male worldwide. Stromal-epithelial interaction is thought to have a major impact on cancer development and progression. Previous studies have shown that interaction via soluble factors lead to a reduction in the expression of xCT and AL122023.
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