Histone acetyltransferase inhibitors: An overview in synthesis, structure-activity relationship and molecular mechanism.

Acetylation, a key component in post-translational modification regulated by HATs and HDACs, is relevant to many crucial cellular contexts in organisms. Based on crucial pharmacophore patterns and the structure of targeted proteins, HAT inhibitors are designed and modified for higher affinity and better bioactivity. However, there are still some challenges, such as cell permeability, selectivity, toxicity and synthetic availability, which limit the improvement of HAT inhibitors.

SARI attenuates colon inflammation by promoting STAT1 degradation in intestinal epithelial cells.

SARI functions as a suppressor of colon cancer and predicts survival of colon cancer patients, but its role in regulating colitis has not been characterized. Here we show that SARI mice were highly susceptible to colitis, which was associated with enhanced macrophage infiltration and inflammatory cytokine production. Bone marrow reconstitution experiments demonstrated that disease susceptibility was not dependent on the deficiency of SARI in the immune compartment but on the protective role of SARI in the intestinal epithelial cells (IECs).

Evaluation of environment safety of a Japanese encephalitis live attenuated vaccine.

JE vaccination is the most effective and economical method of preventing JE. A live attenuated JE vaccine has been widely used in many countries since 1989, playing an important role in controlling JE outbreaks. However, whether the large-scale use of the live attenuated JE vaccine will lead to the dissemination of the vaccine virus in the environment and whether reversion of the neuroattenuation of the virus will occur during the transmission process remain major concerns for some researchers.

Development of a hybrid nanocarrier-recognizing tumor vasculature and penetrating the BBB for glioblastoma multi-targeting therapy.

The success of glioma chemotherapy is hampered by poor drug penetration ability across the blood-brain barrier (BBB) and low intratumoral drug concentration. Novel tumor-targeted delivery systems are useful in specifically accumulating in the tumor foci and penetrating into the glioma core after entering into the brain. Here we show that a multi-targeting hybrid nanocarrier (Pep-MLHA HNPs) system based on hyaluronic acid (HA)-modified polymer and a functional peptide possesses multi-target capability and stronger penetration ability into the core of three-dimensional tumor spheroids, could migrate efficiently across the BBB in vitro.

Visceral Fat Area (VFA) Superior to BMI for Predicting Postoperative Complications After Radical Gastrectomy: a Prospective Cohort Study.

Background: Obesity may impact surgical outcomes of gastrectomy. Whether visceral fat area (VFA) is a better obesity parameter than body mass index (BMI) is still controversial. The aim of this study is to compare the accuracy and effectiveness of VFA and BMI in predicting the short-term surgical outcomes of gastrectomy.

No Evidence for Widespread Positive Selection Signatures in Common Risk Alleles Associated with Schizophrenia.

Schizophrenia poses an evolutionary-genetic paradox as it exhibits strongly negative fitness effects (early mortality and decreased fecundity), yet it persists at a prevalence of approximately 1% worldwide. Evidence from several studies have suggested that schizophrenia is evolved and maintained in part as a maladaptive byproduct of recent positive selection and adaptive evolution in human beings. However, inconsistent results have been also proposed, challenging the recent positive selection theory to explain the high population frequency of schizophrenia-associated alleles.

A general strategy for label-free homogeneous bioassays based on selective recognition and silver ion-mediated conformational switch.

Simple, sensitive, and cost-effective detection of biomolecules is important to clinical analysis and treatment. Herein, a novel fluorescence turn-off method for the homogeneous detection of DNA and proteins was developed using selective recognition reaction and silver ion-mediated conformational switch. In this work, we discovered the new phenomenon that cadmium telluride (CdTe) quantum dots (QDs) could selectively differentiate silver ions (Ag) from the cytosine (C)-Ag-cytosine (C-Ag-C) hairpin structure, owing to the ability of Ag to quench CdTe QDs which the C-Ag-C complex didn't possess.

Bat adeno-associated viruses as gene therapy vectors with the potential to evade human neutralizing antibodies.

The prevalence of adeno-associated virus (AAV) has been investigated in bat populations, but little is known about the biological properties of this virus. In this study, four full-length bat AAV capsid genes were isolated in China, with their amino acid sequences sharing 61% identity with those of AAV2 on average. These capsid genes could package AAV particles in combination with AAV2 rep and ITRs, albeit at a lower efficiency.

Polydiacetylene-Nanoparticle-Functionalized Microgels for Topical Bacterial Infection Treatment.

Clearance of bacteria-secreted toxins can be a benefit to treating bacterial infections. In this study, we show a polydiacetylene (PDA) nanoparticle-functionalized microgel for managing topical bacterial infections. These functional microgels with designed shapes and size are precisely fabricated via a digital light processing (DLP)-based 3D bioprinting process.

A Fluorescence Strategy for Silver Ion Assay via Cation Exchange Reaction and Formation of Poly(thymine)-templated Copper Nanoclusters.

The detection of Ag ions in the environment and biological systems is important to both environmental monitoring and modern medicine. Herein, a novel and label-free method was developed for Ag detection, which utilizes a florescence strategy combining DNA-templated copper nanoclusters (Cu NCs) with cation exchange reactions. The method is primarily based on the effective detection of an Ag-triggered cation exchange reaction and the release of free Cu from CuS nanoparticles (CuS NPs), while the probe T30 serves as an effective template for the formation of fluorescence-inducing Cu NCs.

Zinc finger proteins and regulation of the hallmarks of cancer.

Zinc finger proteins (ZFPs) form one of the largest families of transcription factors in human genetics, via their conserved zinc finger motifs. ZFPs function in many biological processes including development, differentiation, metabolism and apoptosis. In addition, recent studies have demonstrated that ZFPs are closely associated with different stages of cancer development.

LKB1 and YAP phosphorylation play important roles in Celastrol-induced β-catenin degradation in colorectal cancer.

Wnt/β-catenin and Hippo pathways play essential roles in the tumorigenesis and development of colorectal cancer. We found that Celastrol, isolated from plant, exerted a significant inhibitory effect on colorectal cancer cell growth and , and further unraveled the molecular mechanisms. Celastrol induced β-catenin degradation through phosphorylation of Yes-associated protein (YAP), a major downstream effector of Hippo pathway, and also Celastrol-induced β-catenin degradation was dependent on liver kinase B1 (LKB1).

Design, synthesis and biological evaluation of 4-aniline-thieno[2,3-d]pyrimidine derivatives as MNK1 inhibitors against renal cell carcinoma and nasopharyngeal carcinoma.

MAP Kinase Interacting Serine/Threonine Kinase 1 (MNK1) play important roles in the signaling transduction of MAPK pathways. It is significantly overexpressed in renal clear cell carcinoma and head-neck squamous cell carcinoma tissues in both mRNA and protein levels. Based on the crystallographic structure of MNK1 protein and binding modes analysis of known MNK inhibitors, we have designed and synthesized a series of 4-aniline-thieno[2,3-d]pyrimidine derivatives as potential MNK1 inhibitors.

ZY0511, a novel, potent and selective LSD1 inhibitor, exhibits anticancer activity against solid tumors via the DDIT4/mTOR pathway.

Lysine-specific demethylase1 (LSD1) plays a crucial role in cancer and has become a promising target for cancer therapy. However, the mechanism underlying the role of LSD1 in oncogenesis is poorly understood, and more effective LSD1 inhibitors are needed. Here we report the biological activity of a novel LSD1 inhibitor named ZY0511.

Salicylic acid treats acne vulgaris by suppressing AMPK/SREBP1 pathway in sebocytes.

Acne vulgaris is a prevalent cutaneous disease characterized by a multifactorial pathogenic process including hyperseborrhea, inflammation, over-keratinization of follicular keratinocytes and Propionibacterium acnes (P acnes) overgrowth. Salicylic acid (SA), a beta-hydroxy acid, is frequently used in the treatment of acne. SA has been found to decrease skin lipids and to possess anti-inflammatory properties.

Emerging microRNA biomarkers for colorectal cancer diagnosis and prognosis.

MicroRNAs (miRNAs) are one abundant class of small, endogenous non-coding RNAs, which regulate various biological processes by inhibiting expression of target genes. miRNAs have important functional roles in carcinogenesis and development of colorectal cancer (CRC), and emerging evidence has indicated the feasibility of miRNAs as robust cancer biomarkers. This review summarizes the progress in miRNA-related research, including study of its oncogene or tumour-suppressor roles and the advantages of miRNA biomarkers for CRC diagnosis, treatment and recurrence prediction.

Design, synthesis and molecular mechanisms of novel dual inhibitors of heat shock protein 90/phosphoinositide 3-kinase alpha (Hsp90/PI3Kα) against cutaneous melanoma.

Overexpression of heat shock protein 90 (Hsp90) is common in various types of cancer. In cutaneous melanoma, a cancer with one of the high levels of Hsp90 overexpression, such expression was correlated with a panel of protein kinases, thus offering an opportunity to identify Hsp90-based multi-kinase inhibitors for novel cancer therapies. Towards this goal, we utilized a 2,4-dihydroxy-5-isopropylbenzate-based Hsp90 inhibitor scaffold and thieno[2,3-d]pyrimidine-based kinase inhibitor scaffold to develop a Hsp90-inhibiting compound library.

Repositioning antipsychotic fluphenazine hydrochloride for treating triple negative breast cancer with brain metastases and lung metastases.

Triple negative breast cancer (TNBC) patients have a high risk of brain metastases. This deadly disease represents a major challenge for successful treatment, in part because of the poor ability of drugs to penetrate the blood-brain barrier. Antipsychotic drugs show good bioavailability in the brain, and some of them have exhibited anticancer effects in several cancer types.

Evaluation of epigallocatechin-3-gallate (EGCG)-modified scaffold determines macrophage recruitment.

Biomaterials based on the modulation of macrophages have gained increased attention recently. Macrophages are generally divided into the pro-inflammatory M1 and pro-regenerative M2 phenotypes. Macrophages play a pivotal role in bone regeneration by regulating osteoblast differentiation and secreting pro-regenerative factors.

Mitochondrial Surface Engineering for Multidrug Resistance Reversal.

Multidrug resistance (MDR) is still a formidable obstacle for the majority of anticancer drugs during chemotherapy. MDR is generally divided into the pump and nonpump resistances, which significantly and simultaneously reduce drug accumulation and potency in various cancer cells. In order to concurrently combat the two pathways to completely overcome MDR, a novel siRNA-containing nanomaterial-coated mitochondria complex was developed, which can overcome the barrier of activity loss and electrostatic repulsion to effectively deliver siRNA and mitochondria into the MDR cells.

Rapid 3D printing of functional nanoparticle-enhanced conduits for effective nerve repair.

Nerve conduits provide an advanced tool for repairing the injured peripheral nerve that often causes disability and mortality. Currently, the efficiency of conduits in repairing peripheral nerve is unsatisfying. Here, we show a functional nanoparticle-enhanced nerve conduit for promoting the regeneration of peripheral nerves.

Exo-circRNAs: a new paradigm for anticancer therapy.

CircRNAs, as new members of long noncoding RNAs, have been the focus of recent investigation. CircRNAs feature a closed continuous loop structure without 5'-3' polarity or a poly A tail. Many studies have reported the potential application of circRNAs in the clinic as new biomarkers and therapeutic targets in different diseases, especially for cancer.

Discovery and biological evaluation of novel androgen receptor antagonist for castration-resistant prostate cancer.

Prostate cancer (PC) is the second most common malignancy in men worldwide. Among current therapies, two antiandrogens, Abiraterone Acetate and Enzalutamide (Enza) have become the standard of care for patients with metastatic castration-resistant prostate cancer (mCRPC). Here, we designed and synthesized a new series of nonsteroidal compounds deriving from the hybridization of Abiraterone (Abi) and Enzalutamide, among which compound 4a featuring the diphenylamine scaffold was identified as a potent and cell selective androgen receptor (AR) antagonist.