Opposing manner of miR-455-3p against NR2B-PSD-95-nNOS complex in the cortex and hippocampus of depressive rats under simulated complex space environment.

Depression in astronauts is one of the consequences of space flight effects, negatively impacting their work performances. Unfortunately, the underlying molecular mechanisms in space flight-induced depression are still unknown; however, various neuropsychiatric disorders reported that overexpressed NR2B-PSD-95-nNOS complex in the brain triggers various pathological pathways, and inhibiting NR2B-PSD-95-nNOS complex asserts antidepressant effects. Through our in silico analysis, we found that epigenetic regulator miR-445-3p targets PSD-95 and is hypothesized to down-regulate NR2B-PSD-95-nNOS complex to prevent neuronal damage associated with depression.

Design, synthesis and biological evaluation of hydrogen sulfide-releasing isochroman-4-one derivatives as new antihypertensive agent candidates.

Cardiovascular diseases are increasingly threating the global human health, hypertension is the most important risk factor for cardiovascular and cerebrovascular diseases. To improve the antihypertensive activity and cardiovascular protective effect of natural product (±)-7,8-dihydroxy-3-methyl-isochroman-4-one [(±)-XJP], a series of novel HS-releasing isochroman-4-one derivatives were designed and synthesized by coupling hydrogen sulfide (HS)-releasing donors with the analogs of (±)-XJP. Further, the HS-releasing assay indicated that some target compounds showed excellent HS generating ability.

Emerging Potential of Exosomal Non-coding RNA in Parkinson's Disease: A Review.

Exosomes are extracellular vesicles that are released by cells and circulate freely in body fluids. Under physiological and pathological conditions, they serve as cargo for various biological substances such as nucleotides (DNA, RNA, ncRNA), lipids, and proteins. Recently, exosomes have been revealed to have an important role in the pathophysiology of several neurodegenerative illnesses, including Parkinson's disease (PD).

Epigenetic Regulation of Neuroinflammation in Parkinson's Disease.

Neuroinflammation is one of the most significant factors involved in the initiation and progression of Parkinson's disease. PD is a neurodegenerative disorder with a motor disability linked with various complex and diversified risk factors. These factors trigger myriads of cellular and molecular processes, such as misfolding defective proteins, oxidative stress, mitochondrial dysfunction, and neurotoxic substances that induce selective neurodegeneration of dopamine neurons.

Design, synthesis and biological evaluation of isochroman-4-one hybrids bearing piperazine moiety as antihypertensive agent candidates.

7,8-Dihydroxy-3-methyl-isochromanone-4 (XJP), is a polyphenolic natural product with moderate antihypertensive activity. To obtain new agents with stronger potency and safer profile, we employed XJP and naftopidil as the lead compounds to design and synthesize a novel class of hybrids as antihypertensive agent candidates. In the present study, a series of hybrids (6a-r) of XJP bearing arylpiperazine moiety, which is identified as the pharmacophore of naftopidil, were designed and synthesized as novel α-adrenergic receptor antagonists.

Design, synthesis, biological evaluation, and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors (part II).

A series of novel 4-isochromanone compounds bearing N-benzyl pyridinium moiety were designed and synthesized as acetylcholinesterase (AChE) inhibitors. The biological evaluation showed that most of the target compounds exhibited potent inhibitory activities against AChE. Among them, compound 1q possessed the strongest anti-AChE activity with an IC value of 0.

Discovery of hepatitis B virus capsid assembly inhibitors leading to a heteroaryldihydropyrimidine based clinical candidate (GLS4).

Inhibition of hepatitis B virus (HBV) capsid assembly is a novel strategy for the development of chronic hepatitis B (CHB) therapeutics. Herein we described our lead optimization studies including the synthesis, molecular docking studies and structure-activity relationship (SAR) studies of a series of novel heteroaryldihydropyrimidine (HAP) inhibitors of HBV capsid assembly inhibitors, and the discovery of a potent inhibitor of HBV capsid assembly of GLS4 (ethyl 4-[2-bromo-4-fluorophenyl]-6-[morpholino-methyl]-2-[2-thiazolyl]-1,4-dihydro-pyrimidine-5-carboxylate) which is now in clinical phase 2. GLS4 demonstrated potent inhibitory activities in HBV HepG2.

Design, synthesis, biological evaluation and docking study of 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors.

A series of novel 4-isochromanone hybrids bearing N-benzyl pyridinium moiety as dual binding site acetylcholinesterase inhibitors have been designed and synthesized. The screening results showed that most of the compounds exhibited potent anti-AChE activity in the range of nM concentrations. The 1-(4-fluorobenzyl) substituted derivative 9d exhibited the most potent anti-AChE activity with IC50 value of 8.

First total synthesis of antihypertensive natural products S-(+)-XJP and R-(-)-XJP.

The first asymmetric total synthesis of antihypertensive natural products S-(+)-XJP and R-(-)-XJP has been achieved in 8 steps starting from commercially available 6-bromo-2-hydroxy-3-methoxybenzaldehyde. Key steps included intramolecular Heck reaction and oxidative ozonolysis reaction with the retention of stereochemistry. A latent functionality strategy was implemented to circumvent the racemization in this endeavor.

Economical, green and dual-function pyridyl iodides as electrolyte components for high efficiency dye-sensitized solar cells.

Pyridyl iodides were synthesized to serve as effective, economical, green and dual function additives for high efficiency and stable DSCs. Using commercial P25 as the photoanode, a high PCE of 7.81% was achieved with a pyridyl iodide-containing electrolyte.