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Tilianin is a naturally occurring phenolic compound with a cardioprotective effect against myocardial ischemia/reperfusion injury (MIRI). The aim of our study was to determine the potential targets and mechanism of action of tilianin against cardiac injury induced by MIRI. An in silico docking model was used in this study for binding mode analysis between tilianin and Ca2+/calmodulin-dependent protein kinase II (CaMKII). Oxygen-glucose deprivation/reperfusion- (OGD/R-) injured H9c2 cardiomyocytes and ischemia/reperfusion- (I/R-) injured isolated rat hearts were developed as in vitro and ex vivo models, respectively, which were both treated with tilianin in the absence or presence of a specific CaMKII inhibitor KN93 for target verification and mechanistic exploration. Results demonstrated the ability of tilianin to facilitater the recovery of OGD/R-induced cardiomyocyte injury and the maintenance of cardiac function in I/R-injured hearts. Tilianin interacted with CaMKIIδ with an efficient binding performance, a favorable binding score, and restraining p-CaMKII and ox-CaMKII expression in cardiomyocytes injured by MIRI. Importantly, inhibition of CaMKII abolished tilianin-mediated recovery of OGD/R-induced cardiomyocyte injury and maintenance of cardiac function in I/R-injured hearts, accompanied by the disability to protect mitochondrial function. Furthermore, the protective effects of tilianin towards mitochondrion-associated proapoptotic and antiapoptotic protein counterbalance and c-Jun N-terminal kinase (JNK)/nuclear factor- (NF-) κB-related inflammation suppression were both abolished after pharmacological inhibition of CaMKII. Our investigation indicated that the inhibition of CaMKII-mediated mitochondrial apoptosis and JNK/NF-κB inflammation might be considered as a pivotal mechanism used by tilianin to exert its protective effects on MIRI cardiac damage. [ABSTRACT FROM AUTHOR]

• miR-25802 upregulation is involved in the pathological progression of AD. • miR-25802 regulates microglia-mediated neuroinflammation in AD. • miR-25802 targets KLF4 to regulate NF-κB signaling. • The miR-25802/KLF4/NF-κB axis has a regulatory role in cognitive deficits in AD. Microglia-mediated neuroinflammation plays a critical role in the occurrence and progression of Alzheimer's disease (AD). In recent years, studies have increasingly explored microRNAs as biomarkers and treatment interventions for AD. This study identified a novel microRNA termed miR-25802 from our high-throughput sequencing dataset of an AD model and explored its role and the underlying mechanism. The results confirmed the miRNA properties of miR-25802 based on bioinformatics and experimental verification. Expression of miR-25802 was increased in the plasma of AD patients and in the hippocampus of APP/PS1 and 5 × FAD mice carrying two and five familial AD gene mutations. Functional studies suggested that overexpression or inhibition of miR-25802 respectively aggravated or ameliorated AD-related pathology, including cognitive disability, Aβ deposition, microglial pro-inflammatory phenotype activation, and neuroinflammation, in 5 × FAD mice and homeostatic or LPS/IFN-γ-stimulated EOC20 microglia. Mechanistically, miR-25802 negatively regulates KLF4 by directly binding to KLF4 mRNA, thus stimulating microglia polarization toward the pro-inflammatory M1 phenotype by promoting the NF-κB-mediated inflammatory response. The results also showed that inhibition of miR-25802 increased microglial anti-inflammatory M2 phenotype activity and suppressed NF-κB-mediated inflammatory reactions in the brains of 5 × FAD mice, while overexpression of miR-25802 exacerbated microglial pro-inflammatory M1 activity by enhancing NF-κB pathways. Of note, AD-associated manifestations induced by inhibition or overexpression of miR-25802 via the NF-κB signaling pathway were reversed by KLF4 silencing or upregulation. Collectively, these results provide the first evidence that miR-25802 is a regulator of microglial activity and establish the role of miR-25802/KLF4/NF-κB signaling in microglia-mediated neuroinflammation, suggesting potential therapeutic targets for AD. [ABSTRACT FROM AUTHOR]

As the global population ages, the number of patients with osteoporosis is rapidly rising. The existing first-line clinical drugs are bone resorption inhibitors that have difficulty restoring the bone mass of elderly patients to the safe range. The range and period of use of existing peptides and monoclonal antibodies are limited, and small-molecule bone formation–promoting drugs are urgently required. We established an I-9 synthesis route with high yield, simple operation, and low cost that was suitable for future large-scale production. I-9 administration promoted bone formation and increased bone mass in mice with low bone mass in an aged C57 mouse model. Our findings revealed a hitherto undescribed pathway involving the BMP2–ERK–ATF4 axis that promotes osteoblast differentiation; I-9 has favorable biosafety in mice. This study systematically investigated the efficacy, safety, and mechanism of I-9 for treating osteoporosis and positions this drug for preclinical research in the future. Thus, this study has promoted the development of small-molecule bone-promoting drugs. [ABSTRACT FROM AUTHOR]

This document is a correction notice for an article titled "Microarray Profile of Long Noncoding RNA and Messenger RNA Expression in a Model of Alzheimer's Disease." The correction includes updated email addresses for two authors and a mistake in Figure 2 of the original publication. The corrected figure shows the chromosome location distribution of upregulated and downregulated long noncoding RNAs. The authors state that the scientific conclusions are unaffected by the error. [Extracted from the article]

Drug compounds including memantine moieties are an important group of biologically active agents for different pathologies, including the Alzheimer's disease. In the present study, a series of memantine derivatives incorporating amino acid residues have been synthesized and their neuroprotective in vitro evaluation in respect of the Alzheimer's disease, involving the effects on the resistance to Aβ toxicity, excitotoxicity, oxidative stress, hypoxia, and neuroinflammation has been studied. The cytotoxicities of the compounds were detected by CPE assay. TC50 and IC50 were determined using Reed and Muench method. Solubility and distribution were measured using a shake-flask method. Permeability of the compounds was studied using Franz diffusion cell and Permeapad™ barrier. These compounds displayed apparent multi-neuroprotective effects against copper-triggered Aβ toxicity, glutamate-induced excitotoxicity, and oxidative and hypoxic injuries. They also showed the ability to inhibit the inflammatory cytokine release from the activated microglia and potential anti-neuroinflammatory effects. Especially, two most promising compounds H-4-F-Phe-memantine and H-Tyr-memantine demonstrated the equivalent functional bioactivities in comparison with the positive control memantine hydrochloride. Higher solubility in muriatic buffer than in phosphate buffer was detected. The distribution coefficients showed the optimal lipophilicity for compounds. The presented results propose new class of memantine derivatives as potential drug compounds. Based on the experimental results, the correlations have been obtained between the biological, physicochemical parameters and structural descriptors. The correlation equations have been proposed to predict the properties of new memantine derivatives knowing only the structural formula. [ABSTRACT FROM AUTHOR]

Abstract Aims Tilianin, a naturally occurring flavonoid glycoside, possesses versatile biological activities including antioxidant, anti-inflammatory, energy collecting and anti-hypoxic effects. Little is known about the mechanisms underlying the effect of tilianin against ischemic injury in neuronal cells. We aimed to determine the potential targets and mechanisms of tilianin treatment behind the crosstalk pathways induced by oxygen-glucose deprivation (OGD). Main methods We used an in silico docking model for interaction mode analysis and in vitro models for mechanistic exploration and target verification. Protein changes were measured using cellular immunofluorescence and ELISA techniques. Key findings The ability of tilianin to promote recovery of OGD-induced neurocytotoxic injury was demonstrated by maintenance of cell viability, membrane integrity and nuclear homogeneity. Tilianin treatment was also found to balance the concentrations of proapoptotic and antiapoptotic proteins that had been modified by OGD-induced mitochondrial dysfunction. Of these intersectional cascades, Ca2+/calmodulin-dependent protein kinase II (CaMKII) was found to bind efficiently with tilianin. This presented a certain binding score along with down-regulation of ox-CaMKII and p-CaMKII in SH-SY5Y cells affected by OGD. Importantly, after utilizing KN93, one specific CaMKII inhibitor, tilianin-mediated neuroprotection against OGD was abolished. This effect was accompanied by upregulation of mitochondrial function. Thus, the beneficial effects of tilianin toward mitochondrion-mediated apoptosis and p38/JNK/NF-κB-associated inflammatory pathways were reversed following CaMKII inhibition. Significance Our study indicated that attenuation of CaMKII-linked signaling mediated through mitochondria and p38/JNK/NF-κB inflammatory pathways is a key mechanism by which tilianin exerts its neuroprotective effects against cerebral ischemia. [ABSTRACT FROM AUTHOR]

A series of chalcone derivatives bearing benzamide or benzenesulfonamide moieties were synthesized and evaluated for their anti-tumor effect on HCT116, MCF7 and 143B cell lines in vitro . SAR analysis showed that compounds bearing a benzenesulfonamide group had greater potency than those bearing a benzamide group. It was also shown that compounds with a mono-methyl or mono-halogen group at the 3-position on the terminal phenyl ring were more effective than those with trifluoromethyl or methoxy groups. Compound 8e exhibited the most potent anti-tumor activities against HCT116, MCF7 and 143B cell lines, with IC 50 values of 0.597, 0.886 and 0.791 μM, respectively. Molecular docking studies and enzymatic assays demonstrated that the anti-tumor activity of compound 8e might be regulated by Cat L and Cat K. [ABSTRACT FROM AUTHOR]