Previously undescribed tetrahydroanthraquinones from Prismatomeris tetrandra (roxb.) K. Schum with antitumor cell proliferation activities.

To find structurally previously undescribed compounds with pharmacological effects from Prismatomeris tetrandra (Roxb.) K. Schum (Rubiaceae), thirteen undescribed tetrahydroanthraquinones (1⎼13) named prisconnatanones J⎼V and seven known anthraquinones (14⎼20) were isolated and characterized.

Rational design and optimization of novel 4-methyl quinazoline derivatives as PI3K/HDAC dual inhibitors with benzamide as zinc binding moiety for the treatment of acute myeloid leukemia.

Simultaneous inhibition of PI3K and HDAC has shown promise for treating various cancers, leading to discovery and development of their dual inhibitors as novel anticancer agents. Herein, we disclose a new series of PI3K/HDAC dual inhibitors bearing a benzamide moiety as the pharmacophore of HDAC inhibition. Based on systematic structure-activity relationship study, compounds 36 and 51 featuring an alkyl and benzoyl linker respectively were identified with favorable potencies against both PI3K and HDAC.

Exploration and Biological Evaluation of 1,3-Diamino-7-pyrrol[3,2-]quinazoline Derivatives as Dihydrofolate Reductase Inhibitors.

Dihydrofolate reductase (DHFR), a core enzyme of folate metabolism, plays a crucial role in the biosynthesis of purines and thymidylate for cell proliferation and growth in both prokaryotic and eukaryotic cells. However, the development of new DHFR inhibitors is challenging due to the limited number of scaffolds available for drug development. Hence, we designed and synthesized a new class of DHFR inhibitors with a 1,3-diamino-7-pyrrol[3,2-]quinazoline derivative (PQD) structure bearing condensed rings.

Erratum: Author correction to "YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer" [Acta Pharmaceutica Sinica B 12 (2022) 2845-2858].

[This corrects the article DOI: 10.1016/j.apsb.

Involvement of NADPH oxidases in the Na/K‑ATPase/Src/ROS oxidant amplification loop in renal fibrosis.

The Na/K‑ATPase/Src complex is reportedly able to affect reactive oxygen species (ROS) amplification. However, it has remained elusive whether NADPH oxidases (NOXs) are involved in this oxidant amplification loop in renal fibrosis. To test this hypothesis, interactions between oxidative features and Na/K‑ATPase/Src activation were examined in a mouse model of unilateral urethral obstruction (UUO)‑induced experimental renal fibrosis.

S1PR1 serves as a viable drug target against pulmonary fibrosis by increasing the integrity of the endothelial barrier of the lung.

Idiopathic pulmonary fibrosis (IPF) is a progressive lung disease with unclear etiology and limited treatment options. The median survival time for IPF patients is approximately 2-3 years and there is no effective intervention to treat IPF other than lung transplantation. As important components of lung tissue, endothelial cells (ECs) are associated with pulmonary diseases.

Novel nitric oxide-releasing derivatives of pyranocarbazole as antitumor agents: Design, synthesis, biological evaluation, and nitric oxide release studies.

In this study, a series of novel furoxan-based nitric oxide (NO) releasing derivatives of pyranocarbazole alkaloids were designed, synthesized, and biologically evaluated against human cancer cell lines. The derivatives showed considerable antiproliferative activities (IC = 0.05-7.

YPD-30, a prodrug of YPD-29B, is an oral small-molecule inhibitor targeting PD-L1 for the treatment of human cancer.

PD-1 and PD-L1 antibodies have brought about extraordinary clinical benefits for cancer patients, and their indications are expanding incessantly. Currently, most PD-1/PD-L1 agents are administered intravenously, which may be uncomfortable for some cancer patients. Herein, we develop a novel oral-delivered small molecular, YPD-29B, which specifically targets human PD-L1.

Bioevaluation of a dual PI3K/HDAC inhibitor for the treatment of diffuse large B-cell lymphoma.

The synergistic anti-tumor effect by simultaneous inhibitions of PI3K and HDAC has been verified to provide the rationality of PI3K/HDAC dual inhibitors for cancer treatment. Notably, the outstanding effect of PI3K/HDAC dual inhibitors against DLBCL has been paid much attention, especially for RR-DLBCL. Our previously reported 4-methylquinazoine scaffold based PI3K/HDAC dual inhibitors could suppress the growth of solid tumors and hematologic malignancies both in vitro and in vivo, validating the potential as new therapeutic agents for cancer.

Secreted HSP90α-LRP1 Signaling Promotes Tumor Metastasis and Chemoresistance in Pancreatic Cancer.

The extracellular heat shock protein 90α (eHSP90α) has been reported to promote cancer cell motility. However, whether pancreatic cancer (PC) cells expressed membrane-bound or secreted HSP90α, as well as its underlying mechanism for PC progression, were still unclear. Our study demonstrated that the amounts of secreted HSP90α proteins were discrepant in multiple PC cells.

Identification of N, C-capped di- and tripeptides as selective immunoproteasome inhibitors.

A series of N, C-capped di- and tripeptides were designed as selective immunoproteasome inhibitors based on the known inhibitor 4-CA. Forty-eight new compounds were synthesized and evaluated, and the structure-activity relationship (SAR) of this compound class as β5i selective inhibitors were explored. Most of these compounds showed significant inhibition against the β5i subunit of the immunoproteasome and the most potent β5i inhibitor (15) showed an IC of 0.

Association between intrahepatic triglyceride content in subjects with metabolically healthy abdominal obesity and risks of pre-diabetes plus diabetes: an observational study.

Objective: We aimed to evaluate the association of intrahepatic triglyceride (IHTG) content in subjects with metabolically healthy abdominal obesity (MHAO) on risks of pre-diabetes plus diabetes.

Design: Cross-sectional survey.

Setting: Lianqian community, the First Affiliated Hospital of Xiamen University, Xiamen, China.

Associations between serum total bilirubin, obesity and type 2 diabetes.

Background: This study aims to examine the cross-sectional association between serum total bilirubin (STB) and type 2 diabetes (T2D) risk in the general population, and whether obesity could moderate this association.

Methods: We used data from the 1999-2018 National Health and Nutrition Examination Surveys (NHANES), including a total of 38,641 US adult participants who were 18 years or older. The STB was classified as the low, moderate, and high groups according to tertiles.

Joint associations of metabolically healthy abdominal obesity and non-alcoholic fatty liver disease with prediabetes and diabetes in Chinese adults.

Introduction: We aimed to evaluate the joint associations of metabolically healthy abdominal obesity (MHAO) with non-alcoholic fatty liver disease (NAFLD) on risks of diabetes and prediabetes.

Research Design And Methods: Baseline information of 1318 adults with abdominal obesity (waist circumference ≥90 cm for men and 80 cm for women) from an ongoing cohort study in Xiamen, China were analyzed. Metabolic health was identified as none of the criteria of metabolism syndrome, except for obesity, was met.

Identification of 3, 4-disubstituted pyridine derivatives as novel CDK8 inhibitors.

Selective inhibition of cyclin-dependent kinase 8 (CDK8) has been recently regarded as a potential approach for cancer therapy. A series of novel CDK8 inhibitors with the pyridine core was identified via scaffold hopping from the known CDK8 inhibitor A-7. The new inhibitors were designed to improve the ligand efficiency so as to enhance drug-likeness.

Design, synthesis and biological evaluation of dipeptides as novel non-covalent 20S proteasome inhibitors.

Based on the interaction modes of the natural 20S proteasome inhibitors , we have previously discovered a dipeptide . To explore the SAR around compound , we designed and synthesized a series of dipeptides () with a fragment-based strategy. Among them, nine compounds showed significant inhibitory activities against the chymotrypsin-like activity of human 20S proteasome with IC values at the submicromolar level, which were comparable or even superior to the parent compound .

Design, synthesis and biological evaluation of triaryl compounds as novel 20S proteasome inhibitors.

Thirty novel triaryl compounds were designed and synthesized based on the known proteasome inhibitor PI-1840. Most of them showed significant inhibition against the β5c subunit of human 20S proteasome, and five of them exhibited IC values at the sub-micromolar level, which were comparable to or even more potent than PI-1840. The most active two (1c and 1d) showed IC values of 0.

Long non-coding RNA SNHG6 increases JAK2 expression by targeting the miR-181 family to promote colorectal cancer cell proliferation.

Background: Long non-coding RNA (lncRNA) small nucleolar RNA host gene 6 (SNHG6) exerts a regulatory role in cancer biology, although its detailed functions and mechanisms in colorectal cancer (CRC) still remain unclear.

Methods: A quantitative reverse transcriptase-polymerase chain reaction was implemented to investigate the expression of SNHG6, miR-181 family and Janus kinase 2 (JAK2) in CRC tissues and cell lines. The proliferation of CRC cells was detected by a cell counting kit-8 assay, and the apoptosis of CRC cells was determined by flow cytometry analysis.

Silencing of long non-coding RNA CRNDE promotes autophagy and alleviates neonatal hypoxic-ischemic brain damage in rats.

Hypoxic-ischemic (HI) brain damage (HIBD) leads to high neonatal mortality and severe neurologic morbidity. Autophagy is involved in the pathogenesis of HIBD. This study aims to investigate the effect of long non-coding RNA colorectal neoplasia differentially expressed (CRNDE) on HIBD and to validate whether autophagy is involved in this process.

Identification of potential indoleamine 2, 3-dioxygenase 1 (IDO1) inhibitors by an FBG-based 3D QSAR pharmacophore model.

As a rate-limiting enzyme in the major pathway of l-tryptophan catabolism, indoleamine 2, 3-dioxygenase 1 (IDO1) has been regarded as a potential target for the treatment of a variety of diseases. To identify the key molecular features and extend the structural variety of IDO1 inhibitors, a ferrous binding group (FBG)-based 3D-QSAR pharmacophore model was constructed, validated and used for virtual screening herein. The Specs database was initially filtered based on drug-like rules, and was subsequently screened by the pharmacophore model.

Long non-coding RNA CRNDE deteriorates intrauterine infection-induced neonatal brain injury.

Background: This study aimed to test the hypothesis that long non-coding RNA (lncRNA) colorectal neoplasia differentially expressed (CRNDE) could exacerbate brain injury caused by intrauterine infection in neonatal rats.

Methods: Intrauterine infection was induced in pregnant rats by lipopolysaccharide (LPS). After delivery, newborn rats with brain injury caused by intrauterine infection were randomly divided into control, control shRNA, and CRNDE shRNA groups.