Harnessing HDAC-targeted oleanolic acid derivatives for combined anti-cancer and hepatoprotective effects.

The development of anti-tumor drugs with hepatoprotective properties has always been highly valued due to their dual capabilities of safeguarding the liver and combating tumors. Moreover, when used in conjunction with specific chemotherapy drugs, they can enhance the efficacy of cancer treatment while simultaneously reducing liver damage caused by chemotherapeutic agents. Our research focused on oleanolic acid (OA), a natural compound known for its liver-protective effects.

Psychological stress disturbs bone metabolism via miR-335-3p/Fos signaling in osteoclast.

It has been well validated that chronic psychological stress leads to bone loss, but the underlying mechanism remains unclarified. In this study, we established and analyzed the chronic unpredictable mild stress (CUMS) mice to investigate the miRNA-related pathogenic mechanism involved in psychological stress-induced osteoporosis. Our result found that these CUMS mice exhibited osteoporosis phenotype that is mainly attributed to the abnormal activities of osteoclasts.

Design, synthesis and biological evaluation of prostate-specific membrane antigen (PSMA)-targeted SIRT2 inhibitors.

Sirtuins belong to a specific class of enzymes called NAD-dependent protein deacetylases. Among them, SIRT2 is predominantly localized in the cytoplasm and plays a vital role in tumor development and progression. As a result, it becomes an important target for the development of anticancer drugs.

Advances in dual-targeting inhibitors of HDAC6 for cancer treatment.

Histone Deacetylase 6 (HDAC6) is an essential regulator of histone acetylation processes, exerting influence on a multitude of cellular functions such as cell motility, endocytosis, autophagy, apoptosis, and protein trafficking through its deacetylation activity. The significant implications of HDAC6 in diseases such as cancer, neurodegenerative disorders, and immune disorders have motivated extensive investigation into the development of specific inhibitors targeting this enzyme for therapeutic purposes. Single targeting drugs carry the risk of inducing drug resistance, thus prompting exploration of dual targeting therapy which offers the potential to impact multiple signaling pathways simultaneously, thereby lowering the likelihood of resistance development.

High-Throughput Acoustic Ejection Mass Spectrometry with Adjustable Signal Durations.

High-throughput mass spectrometry (MS) has witnessed rapid advancements and has found extensive applications across various disciplines. It enables the fast and accurate analysis of large sample sets, delivering a 10-fold or greater enhancement in analytical throughput when compared to conventional LC-MS methods. However, the signal duration in these high-throughput MS technologies is typically confined to a narrow range, presenting challenges for workflows demanding prolonged signal durations.

Serendipitous discovery of Class I HDAC inhibitors from rational design of molecular glue degraders targeting HDAC.

Zinc-dependent histone deacetylases (HDACs) play an essential role as epigenetic regulators and are becoming increasingly important drug targets for the treatment of cancer. Although five HDAC inhibitors have been approved for treating several cancers, only one of them is a Class I HDAC inhibitor, which may have advantages over pan-HDAC inhibitors due to the various side effects associated with the latter. On the other hand, the emerging strategy of molecular glue degraders offers a unique advantage for targeting therapeutic proteins.

Efficacy of Poria cocos and Alismatis rhizoma against diet-induced hyperlipidemia in rats based on transcriptome sequencing analysis.

Hyperlipidemia, a common metabolic disease, is a risk factor for cardiovascular diseases, Poria cocos (PC) and Alismatis rhizoma (AR) serve as a potential treatment. A systematic approach based on transcriptome sequencing analysis and bioinformatics methods was developed to explore the synergistic effects of PC-AR and identify major compounds and potential targets. The phenotypic characteristics results indicated that the high dose (4.

Psychological stress: neuroimmune roles in periodontal disease.

Periodontitis is a chronic inflammatory disease that starts with pathogenic bacteria and is mediated by a combination of multiple factors. Psychosomatic factors are considered to be one of the most critical risk factors for periodontal disease. Psychological stress may threaten periodontal immune homeostasis in multiple ways by affecting the hypothalamic-pituitary-adrenal cortex system, the locus ceruleus-sympathetic-adrenal medulla system, and the peptidergic nervous system.

Enhanced Water Solubility and Anti-Tumor Activity of Oleanolic Acid through Chemical Structure Modification.

Cancer has been a major health problem in the world in the past decades. It is urgent to develop new, effective and safe drugs for the treatment of cancer. There are many pentacyclic triterpenoids with positive anti-tumor activity and safety in nature.

Zinc-dependent deacetylases (HDACs) as potential targets for treating Alzheimer's disease.

Alzheimer's disease (AD) as the most prevalent dementia type has become one of the greatest threats to the health and life of the elder people worldwide. Although there has been a great effort in the discovery of anti-AD drugs, those approval drugs only demonstrated the temporarily relieving the symptoms without completely stopping the progression of the neuropathology. It is very urgent and reasonable to develop more effective agents against other therapeutic targets.

Histone Deacetylases as Epigenetic Targets for Treating Parkinson's Disease.

Parkinson's disease (PD) is a chronic progressive neurodegenerative disease that is increasingly becoming a global threat to the health and life of the elderly worldwide. Although there are some drugs clinically available for treating PD, these treatments can only alleviate the symptoms of PD patients but cannot completely cure the disease. Therefore, exploring other potential mechanisms to develop more effective treatments that can modify the course of PD is still highly desirable.

Development of a single-step fluorogenic sirtuin assay and its applications for high-throughput screening.

Sirtuins (SIRTs) are a class of nicotinamide adenine dinucleotide (NAD)-dependent histone deacetylases. Since SIRTs have different subcellular locations and different preferences for deacylation activity, SIRTs are not only highly gaining significance in biological functions but also implications in human diseases. Therefore, it is valuable to establish a high-throughput screening method for the rapid and accurate discovery of SIRT modulators.

Knowledge, perception of HIV symptom severity and cervical cancer screening behaviour among women living with HIV in China.

Objective: This study aimed to examine the previous uptake of cervical cancer screening and intention to be screened and its associated factors among women living with HIV in China.

Methods: We conducted a cross-sectional survey of 213 women living with HIV to collect information about cervical cancer screening behaviour, demographics, knowledge about cervical cancer and screening, and perception of HIV symptom severity.

Results: Seventy-eight women living with HIV (36.

Attenuation of NLRP3 Inflammasome Activation by Indirubin-Derived PROTAC Targeting HDAC6.

Histone deacetylase 6 (HDAC6) is a potential therapeutic target for treating several diseases. A recent study revealed that HDAC6 is important for NLRP3 inflammasome activation, suggesting that targeting HDAC6 could be useful for treating many inflammatory disorders. Using the proteolysis targeting chimera (PROTAC) strategy, we herein report an HDAC6 degrader with low cytotoxicity by tethering a selective HDAC6 inhibitor derived from a natural product, indirubin, with pomalidomide, a CRBN E3 ligand.

Indirubin Derivatives as Dual Inhibitors Targeting Cyclin-Dependent Kinase and Histone Deacetylase for Treating Cancer.

To utilize the unique scaffold of a natural product indirubin, we herein adopted the strategy of combined pharmacophores to design and synthesize a series of novel indirubin derivatives as dual inhibitors against cyclin-dependent kinase (CDK) and histone deacetylase (HDAC). Among them, the lead compound with remarkable CDK2/4/6 and HDAC6 inhibitory activity of IC = 60.9 ± 2.

Osteocytes but not osteoblasts directly build mineralized bone structures.

Bone-forming osteoblasts have been a cornerstone of bone biology for more than a century. Most research toward bone biology and bone diseases center on osteoblasts. Overlooked are the 90% of bone cells, called osteocytes.

Synergistic effects of dual growth factor delivery from composite hydrogels incorporating 2-N,6-O-sulphated chitosan on bone regeneration.

A promising strategy to accelerate bone generation is to deliver a combination of certain growth factors to the integration site via a controlled spatial and temporal delivery mode. Here, a composite hydrogel incorporating poly(lactide-co-glycolide) (PLGA) microspheres was accordingly prepared to load and deliver the osteogenic rhBMP-2 and angiogenic rhVEGF in the required manner. In addition, 2-N,6-O-sulphated chitosan (26SCS), which is a synergetic factor of growth factors, was incorporated in the composite hydrogel as well.

Time-Phase Sequential Utilization of Adipose-Derived Mesenchymal Stem Cells on Mesoporous Bioactive Glass for Restoration of Critical Size Bone Defects.

The effective transportation of oxygen, nutrients, and metabolic wastes through new blood vessel networks is key to the survival of engineered constructs in large bone defects. Adipose-derived mesenchymal stem cells (ADSCs), which are regarded as excellent candidates for both bone and blood vessel engineering, are the preferred option for the restoration of massive bone defects. Therefore, we propose to induce ADSCs into osteogenic and endothelial cells differently.

Tailored biomimetic hydrogel based on a photopolymerised DMP1/MCF/gelatin hybrid system for calvarial bone regeneration.

Searching for effective osteoinduction factors with higher specificity and biosafety for the preparation of biomimetic materials, which mimic the natural bone extracellular matrix (ECM), seems to be an optimum strategy for achieving ideal bone regeneration. Dentin matrix protein 1 (DMP1) seems to be a highly promising candidate due to its pleiotropic bio-regulation roles in several bone formation processes including osteoinduction, osteogenesis and biomineralization. In this study, we first generated a novel meso/macro-structured photopolymerised hybrid hydrogel system, in which DMP1 was loaded in mesocellular silica foam (MCF) and then evenly embedded in the photopolymerised gelatin hydrogel.

Evodiamine Inhibits Angiotensin II-Induced Rat Cardiomyocyte Hypertrophy.

Objective: To investigate the effects of evodiamine (Evo), a component of Evodiaminedia rutaecarpa (Juss.) Benth, on cardiomyocyte hypertrophy induced by angiotensin II (Ang II) and further explore the potential mechanisms.

Methods: Cardiomyocytes from neonatal Sprague Dawley rats were isolated and characterized, and then the cadiomyocyte cultures were randomly divided into control, model (Ang II 0.

Rutaecarpine Inhibits Intimal Hyperplasia in A Balloon-Injured Rat Artery Model.

Objective: To investigate the effect and potential mechanisms of rutaecarpine (Rut) in a rat artery balloon-injury model.

Methods: The intimal hyperplasia model was established by rubbing the endothelia with a balloon catheter in the common carotid artery (CCA) of rats. Fifty rats were randomly divided into five groups, ie.

Increased stem cells delivered using a silk gel/scaffold complex for enhanced bone regeneration.

The low in vivo survival rate of scaffold-seeded cells is still a challenge in stem cell-based bone regeneration. This study seeks to use a silk hydrogel to deliver more stem cells into a bone defect area and prolong the viability of these cells after implantation. Rat bone marrow stem cells were mingled with silk hydrogels at the concentrations of 1.

The response of human osteoblasts, epithelial cells, fibroblasts, macrophages and oral bacteria to nanostructured titanium surfaces: a systematic study.

Nanotopography modification is a major focus of interest in current titanium surface design; however, the influence of the nanostructured surface on human cell/bacterium behavior has rarely been systematically evaluated. In this study, a homogeneous nanofiber structure was prepared on a titanium surface (Nano) by alkali-hydrothermal treatment, and the effects of this Nano surface on the behaviors of human MG-63 osteoblasts, human gingival epithelial cells (HGECs) and human gingival fibroblasts (HGFs) were evaluated in comparison with a smooth titanium surface (Smooth) by polishing and a micro-rough titanium surface (Micro) by sandblasting and acid etching. In addition, the impacts of these different surface morphologies on human THP-1 macrophage polarization and attachment were also assessed.

Null Mice Develop a Unique Osteoarthritis-like Phenotype.

Patients with hypophosphatemia rickets (including mutations) develop severe osteoarthritis (OA), although the mechanism is largely unknown. In this study, we first identified the expression of DMP1 in hypertrophic chondrocytes using immunohistochemistry (IHC) and X-gal analysis of knockout--knockin heterozygous mice. Next, we characterized the OA-like phenotype in null mice from 7-week-old to one-year-old using multiple techniques, including X-ray, micro-CT, H&E staining, Goldner staining, scanning electronic microscopy, IHC assays, etc.