Design, synthesis, and evaluation of quinolin-2(1H)-ones as PDE1 inhibitors for the treatment of inflammatory bowel disease.

Inflammatory bowel disease (IBD) is a chronic inflammatory disease that affects the entire gastrointestinal tract. The complex etiology of IBD made it difficult to cure. Phosphodiesterases (PDEs) have garnered significant attention due to their involvement in immune and inflammatory responses in IBD.

Phosphodiesterase 2 (PDE2) inhibitors: an updated patent review (2017-present).

Introduction: PDE2 is a dual-specific enzyme that hydrolyzes two intracellular substrates, cAMP and cGMP. PDE2 is mainly distributed in the brain, which indicates that PDE2 can serve as a potential target for central nervous system diseases without causing other peripheral side effects. Discovery of new mechanisms of PDE2 inhibitors is expected to bring new opportunities for the treatment of central nervous system diseases.

The therapeutic potential of phosphodiesterase 9 (PDE9) inhibitors: a patent review (2018-present).

Introduction: Phosphodiesterase 9 (PDE9) has been demonstrated as a potential target for neurological disorders and cardiovascular diseases, such as Alzheimer's disease and heart failure. For the last few years, a series of PDE9 inhibitors with structural diversities have been developed and patented by researchers and pharmaceutical companies, providing insights into first-in-class therapies of PDE9 drug candidates.

Area Covered: This review provides an overview of PDE9 inhibitors in patents from 2018 to the present.

Complete genome sequence of a novel totivirus isolated from the leaves of Myrica rubra.

Chinese bayberry is a fruit that is appreciated for its taste. A novel totivirus associated with rolling, disfiguring, chlorotic and vein-clearing symptoms on the leaf apices of Chinese bayberry was identified by transcriptome sequencing and reverse transcription PCR (RT-PCR). The complete genome of the virus was determined to be 4959 nucleotides long, and it contains two open reading frames (ORFs).

Myocardial protection of propofol on apoptosis induced by anthracycline by PI3K/AKT/Bcl-2 pathway in rats.

Background: The release of proinflammatory cytokines is inhibited by propofol, which could reduce oxidative stress and suggests that propofol could ameliorate the adverse effects of anthracyclines in myocardial cells as a promising cardioprotective agent. The aim of the study was to evaluate the protective effects of propofol on phosphatidylinositol 3 kinase/protein kinase B/B cell lymphoma 2 (PI3K/AKT/Bcl-2) pathway in cardiomyocyte apoptosis induced by doxorubicin [adriamycin (ADM)] of rat cardiomyocytes .

Methods: The 40 F344 female rats were randomly divided into 4 groups (n=10): treatment control, ADM, Propofol (Prop) and ADM + Prop group.

Stabilization of UCA1 by N6-methyladenosine RNA methylation modification promotes colorectal cancer progression.

Background: UCA1 is frequently upregulated in a variety of cancers, including CRC, and it can play an oncogenic role by various mechanisms. However, how UCA1 is regulated in cancer is largely unknown. In this study, we aimed to determine whether RNA methylation at N6-methyladenosine (m6A) can impact UCA1 expression in colorectal cancer (CRC).

AKR1B10 promotes breast cancer cell proliferation and migration via the PI3K/AKT/NF-κB signaling pathway.

Background: Aberrant expression of Aldo-Keto reductase family 1 member B10 (AKR1B10) was associated with tumor size and metastasis of breast cancer in our published preliminary studies. However, little is known about the detailed function and underlying molecular mechanism of AKR1B10 in the pathological process of breast cancer.

Methods: The relationship between elevated AKR1B10 expression and the overall survival and disease-free survival of breast cancer patients was analyzed by Kaplan-Meier Plotter database.

AKR1B10 protects against UVC-induced DNA damage in breast cancer cells.

The cellular response to DNA damage is crucial for maintaining the integrity and stability of molecular structure. To maintain genome stability, DNA-damaged cells should be arrested so that mutations can be repaired before replication. Although several key components required for this arrest have been discovered, the majority of the pathways are still unclear.

AKR1B10 confers resistance to radiotherapy via FFA/TLR4/NF-κB axis in nasopharyngeal carcinoma.

Nasopharyngeal carcinoma (NPC) is one kind of human head and neck cancers with high incidence in Southern China, Southeast Asia and North Africa. In spite of great innovations in radiation and chemotherapy treatments, the 5-year survival rate is not satisfactory. One of the main reasons is resistance to radiotherapy which leads to therapy failure and recurrence of NPC.

Improved EGFR mutation detection sensitivity after enrichment by Cas9/sgRNA digestion and PCR amplification.

The detection of circulating tumor DNA is important in cancer research and clinical practice. In the present study, we aimed to improve the sensitivity of downstream mutation detection of next-generation sequencing using the clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated protein 9 (Cas9) system to selectively target wild-type fragments but with low or no cleavage activity to mutant fragments, followed by amplification using polymerase chain reaction. We selected different mutant sites of epidermal growth factor receptor gene (EGFR)-exon19 deletions in patients with lung cancer and constructed mixed templates of mutant and wild-type DNA comprising ratios of 10% to 0.

Primerless Amplification for Circulating Tumor DNA Assays.

A primerless amplification suitable for enrichment of particular genotype cfDNA which is a one-dimensional material has been developed. This primerless amplification coordinated by two thermostable enzymes of endonuclease and proofreading polymerase, functions as a genotype switch in analyzing cfDNA. The endonuclease digests the wild-typed fragments into mega-primer and discriminately destroys the wild-type DNA alleles.

A novel long non-coding RNA-KAT7 is low expressed in colorectal cancer and acts as a tumor suppressor.

Background: The abnormal expression of many long non-coding RNAs (lncRNAs) has been reported in the progression of various tumors. However, the potential biological roles and regulatory mechanisms of long non-coding RNAs in the development of colorectal cancer (CRC) have not yet been fully elucidated. Therefore, it is crucial to identify that lncRNAs can be used for the clinical prevention and treatment of CRC.

AKR1B10 promotes breast cancer cell migration and invasion via activation of ERK signaling.

Background: Aldo-keto reductase family 1, member B10 (AKR1B10), is known to be significantly induced in the cells of various cancers such as breast cancer. However, the mechanisms of AKR1B10 promoting tumorigenesis in breast cancer remain unclear. In the present study, we demonstrated the potential role and mechanism of AKR1B10 in the invasion and migration of breast cancer cells.

The role of long non-coding RNAs in nasopharyngeal carcinoma: As systemic review.

Recent development of cutting edge research found that long noncoding RNAs (lncRNAs) plays important roles in carcinogenesis and progression. In Southeast Asia and North Africa, nasopharyngeal carcinoma (NPC) is the most common aggressive squamous cell carcinoma. Nasopharyngeal carcinoma is most frequently occurring in males.

Low expression of Aldo-keto reductase 1B10 is a novel independent prognostic indicator for nasopharyngeal carcinoma.

Background: Nasopharyngeal carcinoma (NPC) is one of the most common human head and neck cancers with high incidence in Southern China, Southeast Asia and North Africa. Because of its nonspecific symptoms, the early diagnosis of NPC is very difficult. The 5-year survival rate is not ideal in spite of great innovations in radiation and chemotherapy treatments.

Aldo-Keto Reductase Family 1 Member B10 Inhibitors: Potential Drugs for Cancer Treatment.

Cytosolic NADPH-dependent reductase AKR1B10 is a member of the aldo-keto reductase (AKR) superfamily. This enzyme is normally expressed in the gastrointestinal tract. However, it is overexpressed in many solid tumors, such as hepatocarcinoma, lung cancer and breast cancer.

Aldo-keto reductase family 1 member B8 is secreted via non-classical pathway.

Mouse aldo-keto reductase family 1 member B8 (AKR1B8) has the highest similarity to human aldo-keto reductase family 1 member B10 (AKR1B10), a secretory protein through lysosomes-mediated non-classical secretory pathway. To identify whether AKR1B8 is secreted through the same pathway, we carried out this study. Self-developed sandwich ELISA and western blot were used to detect AKR1B8 in cells and culture medium of CT-26 murine colon carcinoma cells.

Rapid determination of human globin chains using reversed-phase high-performance liquid chromatography.

Reversed-phase high-performance liquid chromatography (RP-HPLC) of human globin chains is an important tool for detecting thalassemias and hemoglobin variants. The challenges of this method that limit its clinical application are a long analytical time and complex sample preparation. The aim of this study was to establish a simple, rapid and high-resolution RP-HPLC method for the separation of globin chains in human blood.

[Forward genetic screening for zebrafish mutants defective in myelopoiesis].

Objective: To identify zebrafish mutants with myelopoiesis defects by ENU mutagenesis and large-scale forward genetic screening.

Methods: Male zebrafish were mutagenized with N-ethyl N-nitrosourea to induce mutations in the spermatogonial cells to generate the founders, which were outcrossed with AB to raise F1 fish. The F1 fish from different founders were mated to generate the F2 families.

[Forward genetic screening for zebrafish mutants defective in erythropoiesis].

Objective: To screen and identify zebrafish mutants with erythropoiesis defects by N-ethyl-N-nitrosourea (ENU) mutagenesis and large-scale forward genetic screening using beta e 1 as the marker.

Methods: The chemical mutagen ENU was used to treat healthy wild-type male fish (AB strain, F0). The surviving ENU-treated fish were mated with wild-type female fish to generate F1, and further F2 family was generated by F1 family intercross.