The diphenylpyrimidine derivative as a novel HDAC6 inhibitor alleviates atopic dermatitis through anti-inflammatory effects facilitated via TLR4/MAPK, STAT3 and NF-κB pathways.

Atopic dermatitis (AD) is a systemic immune disease that primarily affects infants and children, characterized by recurring severe pruritus and chronic eczema. Studies have demonstrated that histone deacetylase 6 inhibitors (HDAC6is) can exhibit anti-inflammatory activities by regulating the acetylation level of target proteins. Building on these findings, our research focused on a synthetic diphenylpyrimidine derivative, specifically 15b, which we identified as a potent HDAC6i and an effective anti-inflammatory agent.

Plasma membrane-associated calcium signaling modulates zinc homeostasis in Arabidopsis.

Zinc (Zn) is a crucial micronutrient for all organisms, and its deficiency can significantly hamper crop yield and quality. However, the understanding of the regulatory mechanisms involved in plant Zn signal perception and transduction remains limited. In this study, we discovered that the Ca-CBL1/4/5/8/9-CIPK3/9/23/26-ZIP12 signaling module effectively responds to Zn deficiency and regulates Zn homeostasis in Arabidopsis thaliana.

Arabidopsis calcium-dependent protein kinases 4/5/6/11 negatively regulate hydrotropism via phosphorylation of MIZU-KUSSEI1.

Hydrotropism facilitates the orientation of plant roots toward regions of elevated water potential, enabling them to absorb adequate water. Although calcium signaling plays a crucial role in plant response to water tracking, the exact regulatory mechanisms remain a mystery. Here, we employed the Arabidopsis (Arabidopsis thaliana) hydrotropism-specific protein MIZU-KUSSEI1 (MIZ1) as bait and found that calcium-dependent protein kinases 4/5/6/11 (CPK4/5/6/11) interacted with MIZ1 in vitro and in vivo.

Nano co-delivery of doxorubicin and plumbagin achieves synergistic chemotherapy of hepatocellular carcinoma.

Doxorubicin (DOX) is a chemotherapy drug used for hepatocellular carcinoma (HCC) treatment, but its effectiveness can be dramatically dampened by cancer cell chemoresistance. Signal transducer and activator of transcription 3 (STAT3) is implicated with drug resistance in a range of cancers (e.g.

Silencing LY6D Expression Inhibits Colon Cancer in Xenograft Mice and Regulates Colon Cancer Stem Cells' Proliferation, Stemness, Invasion, and Apoptosis via the MAPK Pathway.

This study explored the role of lymphocyte antigen 6 family member D (LY6D) in colon cancer stem cells' (CCSCs) proliferation and invasion. LY6D was knocked down using siRNA, and the down-regulation of LY6D was verified using Western blotting. After LY6D knockdown, CCSCs' proliferation, stemness, and invasion were suppressed, whereas apoptosis was increased.

TaNRAMP3 is essential for manganese transport in Triticum aestivum.

Manganese (Mn) is an essential trace element for almost all living organisms. In plants, Mn deficiency, which is occurs in calcareous soils or alkaline soils, severely limiting crop yields. However, the potential mechanism of Mn transport in Triticum aestivum is still obscure.

Studies on the Light-Induced Phase Transition of CsPbBr Metal Halide Perovskite Materials.

We investigate the internal mechanism of the light-induced phase transition of CsPbBr perovskite materials via density functional theory simulations. Although CsPbBr tends to appear in the orthorhombic structure, it can be changed easily by external stimulus. We find that the transition of photogenerated carriers plays the decisive role in this process.

Diversified cassane family diterpenoids from the leaves of Caesalpinia minax exerting anti-neuroinflammatory activity through suppressing MAPK and NF-κB pathways in BV-2 microglia.

Ethnopharmacological Relevance: Caesalpinia minax Hance, whose seeds are known as "Ku-shi-lian" in China, have been used in Chinese folk medicine for treatment of rheumatism, dysentery, and skin itching. However, the anti-neuroinflammatory constituents of its leaves and their mechanism are rarely reported.

Aim Of The Study: To search for new anti-neuro-inflammatory compounds from the leaves of C.

Discovery of indole-piperazine derivatives as selective histone deacetylase 6 inhibitors with neurite outgrowth-promoting activities and neuroprotective activities.

Novel indole-piperazine derivatives with a hydroxamic acid moiety were designed and synthesized as selective histone deacetylase 6 (HDAC6) inhibitors. In enzymatic assays, all compounds exhibited nanomolar IC values. N-hydroxy-4-((4-(7-methyl-1H-indole-3-carbonyl)piperazin-1-yl)methyl)benzamide, 9c, was the most potent HDAC6 inhibitor (IC, 13.

Bistable insulin response: The win-win solution for glycemic control.

To satisfy both the safety and rapidity of glycemic control, muscles' insulin response must be bistable, as theoretically predicted. Here, we test the bistability hypothesis by combining cellular experiments (to measure the threshold values ) with mathematical modeling (to test the relevance of bistability ). We examine bistability in C2C12 myotubes by both single-cell analysis (Fӧrster resonance energy transfer) and cultured cells analysis (immunoblot).

Highly oxygenated chemical constitutes and rearranged derivatives with neurotrophic activity from Ganoderma cochlear.

Ethnopharmacological Relevance: The morphological characteristics of Ganoderma cochlear (Blume & T. Nees) Bres were identical to G. sinsense J.

Derivatives of sarcodonin A isolated from Sarcodon scabrosus reversed LPS-induced M1 polarization in microglia through MAPK/NF-κB pathway.

Emerging evidence suggests the regulation of microglial phenotype balance between M1 and M2 will be a potential therapeutic strategy for microglia-mediated neuroinflammation in Alzheimer's disease (AD). Herein, we evaluated the anti-neuroinflammatory effects and the underlying mechanism of a natural cyathane diterpenoid sarcodonin A (1) derived from the mushroom Sarcodon scabrosus and its six new derivatives (2-7). Lipopolysaccharide (LPS)-activated primary microglia and microglia cell lines were used as models.

A review of synthetic bioactive tetrahydro-β-carbolines: A medicinal chemistry perspective.

1, 2, 3, 4-Tetrahydro-β-carboline (THβC) scaffold is widespread in many natural products (NPs) and synthetic compounds which show a variety of pharmacological activities. In this article, we reviewed the design, structures and biological characteristics of reported synthetic THβC compounds, and structure and activity relationship (SAR) of them were also discussed. This work might provide a reference for subsequent drug development based on THβC.

Association of Insulin Resistance and β-cell Function With Bone Turnover Biomarkers in Dysglycemia Patients.

Background: The interrelation between glucose and bone metabolism is complex and has not been fully revealed. This study aimed to investigate the association between insulin resistance, β-cell function and bone turnover biomarker levels among participants with abnormal glycometabolism.

Methods: A total of 5277 subjects were involved through a cross-sectional study (METAL study, http://www.

Does aspirin reduce the incidence, recurrence, and mortality of colorectal cancer? A meta-analysis of randomized clinical trials.

Background: Colorectal cancer (CRC) is the third most common diagnosed cancer and the third leading cause of all cancer deaths in the USA. Some evidences are shown that aspirin can reduce the morbidity and mortality of different cancers, including CRC. Aspirin has become a new focus of cancer prevention and treatment research so far; clinical studies, however, found conflicting conclusions of its anti-cancer characteristics.

Discovery of 1,3-Disubstituted 2,5-Diketopiperazine Derivatives as Potent Class I HDACs Inhibitors.

Histone deacetylases (HDACs) as attractive targets in many diseases therapies has been studied extensively, and its application in cancer research is the most important. Here, we developed a series of derivatives containing natural 2,5-diketopiperazine (DKP) skeleton. Several compounds exhibited distinct HDAC1 inhibitory activities, in particular 2a (IC = 405 nM).

Novel 2, 5-diketopiperazine derivatives as potent selective histone deacetylase 6 inhibitors: Rational design, synthesis and antiproliferative activity.

Histone deacetylase 6 (HDAC6) has gained popular attention for its wide participation in various pathological process recently. In this paper, a series of novel derivatives containing 2, 5-diketopiperazine (DKP) skeleton were developed as potent selective HDAC6 inhibitors (sHDAC6is). Most of these compounds exhibited low nanomolar IC values toward HDAC6, and the best compound was 21b (IC = 0.

Cyathane diterpenoids and drimane sesquiterpenoids with neurotrophic activity from cultures of the fungus Cyathus africanus.

Five terpenoids, including two new cyathane diterpenoids neocyathin S (1) and neocyathin T (2), together with three drimane sesquiterpenoids, one known 3β,6β-dihydroxycinnamolide (3), two new ones 3β,6α-dihydroxycinnamolide (4) and 2-keto-3β,6β-dihydroxycinnamolide (5), were isolated from the cultures of the basidiomycete Cyathus africanus. Their structures were established based on extensive spectroscopic methods including 2D NMR (HSQC, H‒H-COSY, HMBC, ROESY) and HRESIMS experiments. The absolute configurations of two pairs of epimers, 1 and 2 as well as 3 and 4, were determined by ECD quantum chemical calculation.

Hyperelatosides A-E, biphenyl ether glycosides from , with neurotrophic activity.

Five new biphenyl ether glycosides, hyperelatosides A-E (1-5), one new benzoate glycoside, hyperelatoside F (6), along with nine known phenolic compounds (7-15), were isolated from the aerial parts of . Their structures were elucidated by 1D and 2D NMR spectroscopy and HRESIMS, as well as chemical derivatization. This is the first report of the identification of biphenyl ether glycosides as plant metabolites and their possible biosynthetic pathway is proposed.

Sarcodonin G Derivatives Exhibit Distinctive Effects on Neurite Outgrowth by Modulating NGF Signaling in PC12 Cells.

Sarcodonin G, one of the cyathane diterpenoids isolated from the mushroom Sarcodon scabrosus, possesses pronounced neurotrophic activity but ambiguous mechanical understanding. In this work, sarcodonin G was chosen as a lead compound to prepare a series of 19- O-benzoyl derivatives by semisynthesis and their neuritogenic activities were evaluated. 6 and 15 (10 μM) were investigated with opposite effects in PC12 cells.

Polyoxygenated cyathane diterpenoids from the mushroom Cyathus africanus, and their neurotrophic and anti-neuroinflammatory activities.

In a previous study, we reported ten new polyoxygenated cyathane diterpenoids, neocyathins A-J, and their anti-neuroinflammatory effects from the liquid culture of the medicinal Basidiomycete Cyathus africanus. In the present study, eight new highly polyoxygenated cyathane diterpenoids, named neocyathins K-R (1-8), were isolated from the solid culture of C. africanus cultivated on cooked rice, together with three known congeners (9-11).

Constructing novel dihydrofuran and dihydroisoxazole analogues of isocombretastatin-4 as tubulin polymerization inhibitors through [3+2] reactions.

[3+2] reactions play a key role in constructing various pharmaceutical moleculars. In this study, using Mn(OAc) mediated and 1,3-dipolar [3+2] cyclization reactions, 38 novel dihydrofuran and dihydroisoxazole analogues of isoCA-4 were synthesized as inhibitors of tubulin polymerization. Among them, compound 6g was found to be the most potent cytotoxic agents against PC-3 cells with IC value of 0.

Chemical Constituents from Hericium erinaceus Promote Neuronal Survival and Potentiate Neurite Outgrowth via the TrkA/Erk1/2 Pathway.

is a culinary-medicinal mushroom used traditionally in Eastern Asia to improve memory. In this work, we investigated the neuroprotective and neuritogenic effects of the secondary metabolites isolated from the MeOH extract of cultured mycelium of and the primary mechanisms involved. One new dihydropyridine compound () and one new natural product () together with five known compounds (,-,) were obtained and their structures were elucidated by spectroscopic analysis, including 2D NMR and HRMS.

Quantum dots modified with quaternized poly(dimethylaminoethyl methacrylate) for selective recognition and killing of bacteria over mammalian cells.

Copper-free click chemistry has been used to graft quaternized poly(dimethylaminoethyl methacrylate) (QPA) modified with azide to the quantum dots (QDs) derived with dibenzocyclooctynes (DBCO). The success of the quaternary ammonium polymer-modified QDs was confirmed by ultraviolet-visible spectrophotometry (UV-Vis), fluorescence spectroscopy, zeta (ζ) potential, size distribution, and transmission electron microscopy (TEM). The QPA-modified QDs exhibited properties of selective recognition and killing of bacteria.