Design, Synthesis, Anticancer Evaluation and In Silico Studies of Imidazole Pyrazine Compounds.

The present study focused on design and synthesis novel imidazolopyrazine derivatives, investigate the effect of them on the proliferation and migration of several human cancer cell lines by CCK-8 method, and interactions with the JAKs by reverse molecular docking. It was found that most of the synthesized imidazolopyrazin derivatives exhibited excellent inhibitory effects towards three tested tutor cells in vitro. Among them, three compounds have IC values much lower than Fluorouracil while show low toxicity to normal cells L-02.

Study on mechanism of transdermal administration of eugenol for pain treatment by network pharmacology and molecular docking technology.

The objective of this study was to explore the pharmacological mechanism of transdermal administration of eugenol (EUG) for pain treatment. Firstly, network pharmacology techniques were employed to identify the potential targets responsible for the analgesic effect of EUG. Subsequently, molecular docking technology was used to validate interactions between EUG and the crystal structure of the core target protein.

Biosynthesis of Enfumafungin-type Antibiotic Reveals an Unusual Enzymatic Fusion Pattern and Unprecedented C-C Bond Cleavage.

Enfumafungin-type antibiotics, represented by enfumafungin and fuscoatroside, belong to a distinct group of triterpenoids derived from fungi. These compounds exhibit significant antifungal properties with ibrexafungerp, a semisynthetic derivative of enfumafungin, recently gaining FDA's approval as the first oral antifungal drug for treating invasive vulvar candidiasis. Enfumafungin-type antibiotics possess a cleaved E-ring with an oxidized carboxyl group and a reduced methyl group at the break site, suggesting unprecedented C-C bond cleavage chemistry involved in their biosynthesis.

MicroRNA let-7 Suppresses Influenza A Virus Infection by Targeting RPS16 and Enhancing Type I Interferon Response.

Given the frequent emergence of drug-resistant influenza virus strains and new highly pathogenic influenza virus strains, there is an urgent need to identify new antiviral drugs and targets. We found that influenza A virus (IAV) infection caused a significant decrease of microRNA let-7 expression in host cells; that overexpression of let-7 increased interferon expression and effectively inhibit IAV infection; and that let-7 targets the 3'-untranslated region (UTR) of the ribosomal protein 16 () gene, decreasing its expression. Knocking down the expression of increased the expression of type I interferon and inhibited viral replication.

Roles of corticotropin-releasing factor signaling in the lateral habenula in anxiety-like and alcohol drinking behaviors in male rats.

Corticotropin-releasing factor (CRF) signaling in the mesocorticolimbic system is known to modulate anxiety-like behavior and alcohol consumption, behaviors that also have been associated with the hyper-glutamatergic state of the lateral habenula (LHb) neurons in rats. However, the role of CRF signaling in the LHb on the glutamate transmission, anxiety-like behaviors and alcohol consumption is unknown. Here, we used male rats that had been consuming alcohol for three months to address this gap in the literature.

Salbutamol combined with budesonide in treatment of pediatric bronchial asthma and its effect on eosinophils.

Background: The aim of this study was to investigate and discuss the salbutamol combined with budesonide in treatment of pediatric bronchial asthma (BA) and its effect on eosinophils (EOS).

Methods: Ninety-eight BA children admitted and treated in our hospital from July 2016 to June 2017 were collected and divided into control group (N.=49) and observation group (N.

Inhibition of the ROS-EGFR Pathway Mediates the Protective Action of Nox1/4 Inhibitor GKT137831 against Hypertensive Cardiac Hypertrophy via Suppressing Cardiac Inflammation and Activation of Akt and ERK1/2.

Oxidative stress, inflammation, and hypertension constitute a self-perpetuating vicious circle to exacerbate hypertension and subsequent hypertensive cardiac hypertrophy. NADPH oxidase (Nox) 1/4 inhibitor GKT137831 alleviates hypertensive cardiac hypertrophy in models of secondary hypertension; however, it remains unclear about its effect on hypertensive cardiac hypertrophy in models of essential hypertension. This study is aimed at determining the beneficial role of GKT137831 in hypertensive cardiac hypertrophy in spontaneously hypertensive rats (SHRs) and its mechanisms of action.

Anxiety during alcohol withdrawal involves 5-HT2C receptors and M-channels in the lateral habenula.

Anxiety disorders often co-occur with alcohol use disorders, but the mechanisms underlying this comorbidity remain elusive. Previously, we reported that rats withdrawn from chronic alcohol consumption (Post-EtOH rats) exhibited robust anxiety-like behaviors (AB), which were accompanied by neuronal hyperexcitability, and the downregulation of M-type potassium channels (M-channels) in the lateral habenula (LHb); and that serotonin (5-HT) stimulated LHb neurons via type 2C receptors (5-HTRs). Also, 5-HTR activation is known to inhibit M-current in mouse hypothalamic neurons.

Differences between male and female rats in alcohol drinking, negative affects and neuronal activity after acute and prolonged abstinence.

Alcohol consumption afflicts men and women differently. However, the underlying neuronal mechanisms that contribute to the difference are mostly unexplored. Although more men suffer from alcohol use disorders (AUD), women more frequently accelerate to dependence and develop adverse consequences of alcoholism sooner than men.

Adaptation in 5-HT receptors-CaMKII signaling in lateral habenula underlies increased nociceptive-sensitivity in ethanol-withdrawn rats.

Alcoholics often experience hyperalgesia, especially during abstinence, yet the underlying cellular and molecular bases are unclear. Recent evidence suggests that 5-HT type 2 receptors (5-HTRs) at glutamatergic synapses on lateral habenula (LHb) neurons may play a critical role. We, therefore, measured paw withdrawal responses to thermal and mechanical stimuli, and alcohol intake in a rat model of intermittent drinking paradigm, as well as spontaneous glutamatergic transmission (sEPSCs), and firing of LHb neurons in brain slices.

Alcohol withdrawal drives depressive behaviors by activating neurons in the rostromedial tegmental nucleus.

Rostromedial tegmental nucleus (RMTg) GABA neurons exert a primary inhibitory drive onto midbrain dopamine neurons and are excited by a variety of aversive stimuli. There is, however, little evidence that the RMTg-ventral tegmental area (VTA)-nucleus accumbens shell (Acb) circuit plays a role in the aversive consequences of alcohol withdrawal. This study was performed in adult male Long-Evans rats at 48-h withdrawal from chronic alcohol drinking in the intermittent schedule.

Low-dose ethanol excites lateral habenula neurons projecting to VTA, RMTg, and raphe.

It is unclear how social drinking can contribute to the development of addiction in susceptible individuals. However, alcohol's aversive properties are a well-known factor contributing to its abuse. The lateral habenula (LHb) is a key brain structure responding to various aversive stimuli, including those related to alcohol.

Neoproterozoic rifting in the Upper Yangtze Continental Block: Constraints from granites in the Well W117 borehole, South China.

Well W117 in the Sichuan Basin reveals a suite of ~814 Ma quartz monzonites, unconformably overlain by Sinian clastic and carbonate sediments. The quartz monzonites contain no muscovite and amphibole, and are characterized by high SiO (72.26-77.

Autoantibodies to NR2A Peptide of the Glutamate/NMDA Receptor in Patients with Seizure Disorders in Neuropsychiatric Systemic Lupus Erythematosus.

. Seizure disorders are one of the most disabling, life-threatening, and the least understood syndromes associated with neuropsychiatric SLE (NPSLE). N-Methyl-D-aspartate (NMDA) receptors are a subgroup of the glutamate receptor family, whose NR2A subunit was found on neuronal cells (anti-NR2A) in NPSLE patients with different types of epilepsy.