HDAC3 inhibitors induce drug resistance by promoting IL-17 A production by T cells.

HDAC3 has been demonstrated to play a crucial role in the progression of various tumors and the differentiation and development of T cells. However, its impact on peripheral T cells in the development of murine lung cancer remains unclear. In this experiment, a subcutaneous lung tumor model was established in C57BL/6 mice, and tumor-bearing mice were treated with the specific inhibitor of HDAC3, RGFP966, at different doses to observe changes in tumor size.

Discovery of Novel Dual Inhibitors Targeting Mutant IDH1 and NAMPT for the Treatment of Glioma with IDH1Mutation.

The targeting of cancer cell intrinsic metabolism has emerged as a promising strategy for antitumor intervention. In the study, we identified the first-in-class small molecules that effectively inhibit both mutant isocitrate dehydrogenase 1 (mIDH1) and nicotinamide phosphoribosyltransferase (NAMPT), two crucial targets in cancer metabolism, through structure-based drug design. Notably, compound exhibits excellent and balanced inhibitory activities against both mIDH1 (IC = 14.

Harvesting Vibration Energy for Efficient Cocatalyst-Free Sonocatalytic H Production over Magnetically Separable Ultra-Low-Cost FeO.

The cavitation effect is an important geochemical phenomenon, which generally exists under strong hydrodynamic conditions. Therefore, developing an economical and effective sonocatalyst becomes a vital method in capitalizing on the cavitation effect for energy generation. In this study, we first report a novel FeO sonocatalyst that can be easily separated using a magnetic field and does not require any additional cocatalysts for H production from HO.

A pancancer analysis of histone deacetylase 3 in human tumors.

Background: Histone deacetylase 3 () is known to be an important role in various kinds of cancer, but its effect has not been examined on the pancancer level. Thus, a systematic pancancer analysis was conducted to explore its potential role in pancancer diagnosis, prognosis, and immune correlation research.

Methods: We used a series of databases including The Cancer Genome Atlas (TCGA), Genotype-Tissue Expression (GTEx) Project, The University of Alabama at Birmingham Cancer data analysis portal (UALCAN), Tumor Immune Estimation Resource (TIMER), and Search Tool for the Retrieval of Interacting Genes/Proteins (STRING), among others, to analyze the relationship between the expression of and the diagnosis and prognosis of cancer, the tumor microenvironment (TME), immune infiltration, tumor mutational burden (TMB), microsatellite instability (MSI), mismatch repair (MMR) system using various bioinformatics methods.

Drug discovery targeting nicotinamide phosphoribosyltransferase (NAMPT): Updated progress and perspectives.

Nicotinamide phosphoribosyltransferase (NAMPT) is a key rate-limiting enzyme in the nicotinamide adenine dinucleotide (NAD) salvage pathway, primarily catalyzing the synthesis of nicotinamide mononucleotide (NMN) from nicotinamide (NAM), phosphoribosyl pyrophosphate (PRPP), and adenosine triphosphate (ATP). Metabolic diseases, aging-related diseases, inflammation, and cancers can lead to abnormal expression levels of NAMPT due to the pivotal role of NAD in redox metabolism, aging, the immune system, and DNA repair. In addition, NAMPT can be secreted by cells as a cytokine that binds to cell membrane receptors to regulate intracellular signaling pathways.

Defect Engineered Microcrystalline Cellulose for Enhanced Cocatalyst-Free Piezo-Catalytic H Production.

Mechanical energy driven piezocatalytic hydrogen (H ) production is a promising way to solve the energy crisis . But limited by the slow separation and transfer efficiency of piezoelectric charges generated on the surface of piezocatalysts , the piezocatalytic performance is still not satisfactory. Here, defect engineering is first used to optimize the piezocatalytic performance of microcrystalline cellulose (MCC).

Overview of Methionine Adenosyltransferase 2A (MAT2A) as an Anticancer Target: Structure, Function, and Inhibitors.

Methionine adenosyltransferase 2A (MAT2A) is a rate-limiting enzyme in the methionine cycle that primarily catalyzes the synthesis of -adenosylmethionine (SAM) from methionine and adenosine triphosphate (ATP). MAT2A has been recognized as a therapeutic target for the treatment of cancers. Recently, a few MAT2A inhibitors have been reported, and three entered clinical trials to treat solid tumorsor lymphoma with loss.

A combination of bioinformatics analysis and rational design strategies to enhance keratinase thermostability for efficient biodegradation of feathers.

Keratinase has shown great significance and application potentials in the biodegradation and recycle of keratin waste due to its unique and efficient hydrolysis ability. However, the inherent instability of the enzyme limits its practical utilization. Herein, we obtained a thermostability-enhanced keratinase based on a combination of bioinformatics analysis and rational design strategies for the efficient biodegradation of feathers.

Estimation of PM mortality burden in China with new exposure estimation and local concentration-response function.

The estimation of PM-related mortality is becoming increasingly important. The accuracy of results is largely dependent on the selection of methods for PM exposure assessment and Concentration-Response (C-R) function. In this study, PM observed data from the China National Environmental Monitoring Center, satellite-derived estimation, widely collected geographic and socioeconomic information variables were applied to develop a national satellite-based Land Use Regression model and evaluate PM exposure concentrations within 2013-2015 with the resolution of 1 km × 1 km.

Regulation of an antisense RNA with the transition of neonatal to IIb myosin heavy chain during postnatal development and hypothyroidism in rat skeletal muscle.

Postnatal development of fast skeletal muscle is characterized by a transition in expression of myosin heavy chain (MHC) isoforms, from primarily neonatal MHC at birth to primarily IIb MHC in adults, in a tightly coordinated manner. These isoforms are encoded by distinct genes, which are separated by ∼17 kb on rat chromosome 10. The neonatal-to-IIb MHC transition is inhibited by a hypothyroid state.

Calcineurin plays a modulatory role in loading-induced regulation of type I myosin heavy chain gene expression in slow skeletal muscle.

The role of calcineurin (Cn) in skeletal muscle fiber-type expression has been a subject of great interest because of reports indicating that it controls the slow muscle phenotype. To delineate the role of Cn in phenotype remodeling, particularly its role in driving expression of the type I myosin heavy chain (MHC) gene, we used a novel strategy whereby a profound transition from fast to slow fiber type is induced and examined in the absence and presence of cyclosporin A (CsA), a Cn inhibitor. To induce the fast-to-slow transition, we first subjected rats to 7 days of hindlimb suspension (HS) + thyroid hormone [triiodothyronine (T(3))] to suppress nearly all expression of type I MHC mRNA in the soleus muscle.

Intergenic bidirectional promoter and cooperative regulation of the IIx and IIb MHC genes in fast skeletal muscle.

This study investigated the dynamic regulation of IIx-IIb MHC genes in the fast white medial gastrocnemius (WMG) muscle in response to intermittent resistance exercise training (RE), a model associated with a rapid shift from IIb to IIx expression (11). We investigated the effect of 4 days of RE on the transcriptional activity across the skeletal MHC gene locus in the WMG in female Sprague-Dawley rats. Our results show that RE resulted in significant shifts from IIb to IIx observed at both the pre-mRNA and mRNA levels.

Intergenic transcription and developmental regulation of cardiac myosin heavy chain genes.

Cardiac myosin heavy chain (MHC) gene expression undergoes a rapid transition from beta- to alpha-MHC during early rodent neonatal development (0-21 days of age). Thyroid hormone (3,5,3'-triiodothyronine, T(3)) is a major player in this developmental shift; however, the exact mechanism underlying this transition is poorly understood. The goal of this study was to conduct a more thorough analysis of transcriptional activity of the cardiac MHC gene locus during the early postnatal period in the rodent, in order to gain further insight on the regulation of cardiac MHC genes.

IIx myosin heavy chain promoter regulation cannot be characterized in vivo by direct gene transfer.

In skeletal muscle of the adult mammal IIx is a pivotal myosin heavy chain (MHC) isoform that can be either up- or downregulated depending on both the fiber type of the target muscle and the type of external stimulus imposed. Since little is known about promoter elements of the IIx MHC gene that are important for its transcriptional regulation in vivo,the main goal of this study was to characterize IIx MHC promoter activity and identify potential regulatory elements on the IIx MHC promoter. A direct gene transfer approach was used, and this approach involved transfection of promoter-reporter constructs into intact rat soleus and plantaris muscle under control and denervated conditions, as well as hindlimb suspension (i.

Potential pitfalls in the accuracy of analysis of natural sense-antisense RNA pairs by reverse transcription-PCR.

Background: The ability to accurately measure patterns of gene expression is essential in studying gene function. The reverse transcription polymerase chain reaction (RT-PCR) has become the method of choice for the detection and measurement of RNA expression patterns in both cells and small quantities of tissue. Our previous results show that there is a significant production of primer-independent cDNA synthesis using a popular RNase H- RT enzyme.

Activity of the beta-myosin heavy chain antisense promoter responds to diabetes and hypothyroidism.

Two genes encoding cardiac myosin heavy chain (MHC) isoforms, beta and alpha, are arranged in tandem 4.5 kb apart. We examined pre-mRNA and mature mRNA levels of beta and alpha genes in control, diabetic (streptozotocin), hypothyroid (propylthiouracil), and hyperthyroid rat hearts and analyzed the naturally occurring antisense (AS) beta RNA species that starts in the middle of the 4.

Dynamics of myosin heavy chain gene regulation in slow skeletal muscle: role of natural antisense RNA.

The evolutionarily conserved order of the skeletal muscle myosin heavy chain (MHC) genes and their close tandem proximity on the same chromosome are intriguing and may be important for their coordinated regulation. We investigated type II MHC gene regulation in slow-type muscle fibers undergoing a slow to fast MHC transformation in response to inactivity, 7 days after spinal cord isolation (SI) in rats. We examined the transcriptional products of both the sense and antisense strands across the IIa-IIx-IIb MHC gene locus.

Effect of unloading on type I myosin heavy chain gene regulation in rat soleus muscle.

Slow-twitch soleus, a weight-bearing hindlimb muscle, predominantly expresses the type I myosin heavy chain (MHC) isoform. However, under unloading conditions, a transition in MHC expression occurs from slow type I toward the fast-type isoforms. Transcriptional processes are believed to be involved in this adaptation.

Cloning and sequencing of myosin heavy chain isoform cDNAs in golden-mantled ground squirrels: effects of hibernation on mRNA expression.

The golden-mantled ground squirrel is a small rodent hibernator that demonstrates unusual myosin heavy chain (MHC) isoform plasticity during several months of torpor, punctuated by bouts of rewarming and shivering thermogenesis. We measured MHC mRNA levels to determine whether pretranslational control mechanisms were responsible for differences in MHC2x protein expression, as we previously observed between active and hibernating ground squirrels. We first cloned cDNA using the 3' rapid amplification of cDNA ends (3' RACE) technique and identified three sequences corresponding to MHC1, MHC2x, and MHC2b.

Effect of cyclosporin A treatment on the in vivo regulation of type I MHC gene expression.

Rat soleus muscle consists predominantly of slow type I fibers. We have shown previously through deletion analysis that the highest level of reporter activity that we measure when injecting type I myosin heavy chain (MHC) promoter (MHC(1))-linked luciferase plasmid into soleus muscles depends on the presence of a 550-bp upstream enhancer (3,450-2,900) region of the promoter. Because the calcineurin-nuclear factor of activated T cells (NFAT) pathway has been implicated in the regulation of the slow muscle gene program, particularly the MHC(1) isoform, and the MHC(1) promoter contains several putative NFAT sites, we examined via deletion and mutation analyses whether this pathway is involved in the regulation of promoter activity in soleus.

Role of antisense RNA in coordinating cardiac myosin heavy chain gene switching.

A novel mechanism of regulation of cardiac alpha and beta myosin heavy chain gene by naturally occurring antisense transcription was elucidated via pre-mRNA analysis. Herein, we report the expression of an antisense beta myosin heavy chain RNA in the normal rodent myocardium. The pattern of expression of the antisense betaMHC RNA (beta RNA) under altered thyroid state and in diabetes directly correlates with that of the alpha pre-mRNA/mRNA, whereas it negatively correlates with the beta mRNA expression.

Functional overload increases beta-MHC promoter activity in rodent fast muscle via the proximal MCAT (betae3) site.

Functional overload (OL) of the rat plantaris muscle by the removal of synergistic muscles induces a shift in the myosin heavy chain (MHC) isoform expression profile from the fast isoforms toward the slow type I, or, beta-MHC isoform. Different length rat beta-MHC promoters were linked to a firefly luciferase reporter gene and injected in control and OL plantaris muscles. Reporter activities of -3,500, -914, -408, and -215 bp promoters increased in response to 1 wk of OL.