Inhibitory effect of a novel Curcumin derivative DMC-HA on keloid fibroblasts.

Keloids pose a significant dermatological challenge, marked by abnormal fibroblast proliferation and excessive collagen deposition in response to skin injury or trauma. In the present study, we introduce DMC-HA, a derivative of Curcumin, as a promising candidate for keloid treatment. DMC-HA is poised to provide superior therapeutic benefits compared to Curcumin due to its structural modifications. Examining the comparative effects of DMC-HA and Curcumin on keloid fibroblasts can offer insights into their potential as therapeutic agents and the underlying mechanisms in keloid pathogenesis. In our study, CCK-8 experiments revealed that, at equivalent concentrations, DMC-HA demonstrated greater efficacy in inhibiting the proliferation of keloid fibroblasts compared to Curcumin. Flow cytometry analysis indicated that DMC-HA induced fibroblast apoptosis more significantly than Curcumin at the same concentration. Further data demonstrated that DMC-HA notably increased the production of reactive oxygen species (ROS), upregulated the expression levels of Bax, cleaved PARP, and cleaved Caspase-3. Interestingly, the impact of DMC-HA was reversed upon the application of the antioxidant NAC. Additionally, DMC-HA could suppress IL-6-induced increased expression of p-STAT3. Collectively, our findings suggest that DMC-HA is more effective than Curcumin in inhibiting the proliferation of keloid fibroblasts. The underlying mechanism of its action appears to be associated with the augmentation of ROS induction and the concurrent inhibition of STAT3 activation.

Promising antitumor effects of the curcumin analog DMC-BH on colorectal cancer cells.

Colorectal cancer (CRC) is a common malignant tumor of the digestive system worldwide. DMC-BH, a curcumin analog, has been reported to possess anticancer properties against human gliomas. However, its effects and mechanism on CRC cells are still unknown. Our present study demonstrated that DMC-BH had stronger cytostatic ability than curcumin against CRC cells in vitro and in vivo. It effectively inhibited the proliferation and invasion and promoted the apoptosis of HCT116 and HT-29 cells. RNA-Seq and data analysis indicated that its effects might be mediated by regulation of the PI3K/AKT signaling. Western blotting further confirmed that it dose-dependently suppressed the phosphorylation of PI3K, AKT and mTOR. The Akt pathway activator SC79 reversed the proapoptotic effects of DMC-BH on CRC cells, indicating that its effects are mediated by PI3K/AKT/mTOR signaling. Collectively, the results of the present study suggest that DMC-BH exerts more potent effects than curcumin against CRC by inactivating the PI3K/AKT/mTOR signaling pathway.

Selective Formal Carbene Insertion into Carbon-Boron Bonds of Diboronates by N-Trisylhydrazones.

Bisborylalkanes play important roles in organic synthesis as versatile bifunctional reagents. The two boron moieties in these compounds can be selectively converted into other functional groups through cross-coupling, oxidation or radical reactions. Thus, the development of efficient methods for synthesizing bisborylalkanes is highly demanded. Herein we report a new strategy to access bisborylalkanes through the reaction of N-trisylhydrazones with diboronate, in which the bis(boryl) methane is transformed into 1,2-bis(boronates) via formal carbene insertion. Since the N-trisylhydrazones can be readily derived from the corresponding aldehydes, this strategy represents a practical synthesis of 1,2-diboronates with broad substrate scope. Mechanistic studies reveal an unusual neighboring group effect of 1,1-bis(boronates), which accounts for the observed regioselectivity when unsymmetric 1,1-diboronates are applied.

Generation of α-Boryl Radicals and Their Conjugate Addition to Enones: Transition-Metal-Free Alkylation of gem-Diborylalkanes.

A transition-metal-free method for the alkylation of gem-diborylalkanes with α,ß-unsaturated ketones has been developed. It is demonstrated that the α-boryl radicals can be generated efficiently from gem-diborylalkanes with the aid of catechol and oxidants. The α-boryl radicals formed through such process can be engaged in conjugate addition reaction with α,ß-unsaturated ketones. This transformation is a straightforward method for the synthesis of γ-borylketones.

MiR-5787 Attenuates Macrophages-Mediated Inflammation by Targeting TLR4/NF-κB in Ischemic Cerebral Infarction.

Accumulating studies have suggested the important role of microRNA (miRNA) in ischemic cerebral infarction. However, little is known of the modifying effect of miR-5787, a newly found miRNA, in ischemic cerebral infarction. We aim to elucidate the effect and underlying molecular mechanism of miR-5787 in the pathogenesis of ischemic cerebral infarction. MiR-5787 is demonstrated to be downregulated in peripheral blood mononuclear cells (PBMCs) samples of patients compared with controls, which is negatively associated with inflammatory cytokines of IL-6 and TNF-α in ischemic cerebral infarction. Besides, the expression of miR-5787 is also negatively related to TLR4, which is unregulated in PBMCs of ischemic cerebral infarction patients. Moreover, TLR4 is demonstrated to be a target of miR-5787 by bioinformatics' analysis and the luciferase reporter assay. In addition, miR-5787 can prevent from the proliferation and migration of macrophages, and attenuate LPS/TLR4-mediated inflammatory response via NF-κB in macrophages. MiR-5787 may be a promising biomarker for ischemic cerebral infarction.

Metal-free synthesis of gem-silylboronate esters and their Pd(0)-catalyzed cross-coupling with aryliodides.

A transition-metal-free method for the synthesis of gem-silylboronate esters with arylboronic acids and trimethylsilyldiazomethane (TMSCHN2) has been developed. This transformation is a straightforward homologation of arylboronic acids and features wide substrate scope and good functional-group tolerance. The gem-silylboronate esters undergo efficient Suzuki-Miyaura cross-coupling with aryliodides and the silyl group of the product can be further functionalized. Tertiary carbon centers with different substituents can be constructed successfully by selective and sequential functionalization.

Magnesium Lithospermate B Suppresses Lipopolysaccharide-Induced Neuroinflammation in BV2 Microglial Cells and Attenuates Neurodegeneration in Lipopolysaccharide-Injected Mice.

Chronic inflammation in the brain plays a critical role in major neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), and multiple sclerosis (MS). Microglia, the resident macrophages and intrinsic components of the central nervous system (CNS), appear to be the main effectors in this pathological process. Magnesium lithospermate B (MLB) is one of the major bioactive components of Radix Salviae miltiorrhizae, which has been documented to protect neurons against multiple types of neuronal injury. However, its functions on microglia and the related neuroinflammation remain unknown. In the present study, BV2 microglial cells were used to assess the anti-neuroinflammatory capacity of MLB. Our data show that treatment with MLB could not only suppress lipopolysaccharide (LPS)-induced proliferation and morphological changes, but also interfere with cell cycle progression in BV2 cells. More strikingly, it attenuated the production of the inflammatory mediator nitric oxide (NO) and a panel of pro-inflammatory cytokine in LPS-stimulated BV2 cells, including tumor necrosis factor-α (TNF-α), interleukin (IL)-1α, IL-1ß, and IL-6, and also promoted a phenotypic switch from the M1 to the M2 phenotype. Additionally, an in vivo study showed that the administration of MLB could ameliorate lipopolysaccharide-induced neurodegeneration and microglial activation in the hippocampus of adult mice. Mechanistically, MLB blocked the activation of the NF-κB pathway upon LPS stimulation, indicating that the effects of MLB on microglia may be mediated by the NK-κB pathway. These results suggest the therapeutic potential of MLB as a novel anti-inflammatory and microglia-modulating drug for neurodegenerative diseases.