Paeoniflorin inhibits hepatocellular carcinoma growth by reducing PD-L1 expression.

Abnormal expression of programmed death-ligand 1 (PD-L1) on cancer cells contributes to immune escape in hepatocellular carcinoma (HCC). Paeoniflorin has been shown to inhibit the growth of HCC; however, whether its inhibitory effect involves reducing PD-L1 expression on HCC cells remains unknown. We investigated the antitumor effects of paeoniflorin and its potential regulatory mechanisms in HCC.

Evaluation of the effectiveness and mechanism of action of the Chang-Kang-Fang formula combined with bifid triple viable capsules on diarrhea-predominant irritable bowel syndrome.

Introduction: The Chang-Kang-Fang (CKF) formula, a traditional Chinese herbal formula, can decrease serotonin (5-HT) levels and treat irritable bowel syndrome (IBS). Probiotics have a better synergistic effect on diarrhea-predominant IBS (IBS-D) when combined with 5-HT receptor antagonists. The present study aimed to elucidate the efficacy and the mechanisms of action of the CKF formula combined with bifid triple viable capsules (PFK) against IBS-D.

A comparative study of the ameliorative effects of hyaluronic acid oligosaccharides and hyaluronic acid on DSS-induced colitis in mice and research on relevant mechanisms.

As a dietary supplement, hyaluronic acid (HA) has exhibited appreciable immunomodulatory activity and an ameliorative effect on rodent colitis. However, its high viscosity is not only refractory to absorb through the gut, but also causes flatulence. In contrast to HA, hyaluronic acid oligosaccharides (o-HAs) can overcome the above-mentioned constraints, but their treatment effect still remains ill-defined contemporarily.

Experimental Investigation of the Dynamic Mechanical Properties of Polypropylene-Fiber-Reinforced Foamed Concrete at High Temperatures.

Polypropylene-fiber-reinforced foamed concrete (PPFRFC) is often used to reduce building structure weight and develop engineering material arresting systems (EMASs). This paper investigates the dynamic mechanical properties of PPFRFC with densities of 0.27 g/cm, 0.

Discovery of pyrazolo[3,4-b]pyridine derivatives as novel and potent Mps1 inhibitors for the treatment of cancer.

Monopolar spindle kinase 1 (Mps1) is a key element of the mitotic checkpoint and clinically evaluated as a target in the treatment of aggressive tumors. With this aim, a set of pyrazolo[3,4-b]pyridine-based compounds as new Mps1 inhibitors was investigated through a multidisciplinary approach, based on virtual screening, chemical synthesis and biological evaluation. One of the representative compounds, 31, exhibited strong kinase inhibitory potency against Mps1 with an IC value of 2.

Shaoyao decoction restores the mucus layer in mice with DSS-induced colitis by regulating Notch signaling pathway.

Ethnopharmacological Relevance: Restoring the mucus layer is a potential strategy for treating ulcerative colitis (UC). Previous studies reported that a Chinese medicine formula Shaoyao Decoction (SYD) effectively improved UC. However, the role and mechanism of SYD in restoring the mucus layer are still vague.

Aloin A prevents ulcerative colitis in mice by enhancing the intestinal barrier function via suppressing the Notch signaling pathway.

Background: Previous studies reported that Aloe vera ameliorated DSS-induced colitis and promoted mucus secretion. However, the effect of Aloin A (AA), a major compound of Aloe vera, on colitis and its exact mechanism remains uncovered.

Methods: C57BL/6 mice were successively subjected to 3% DSS solution for 5 days and distilled water for 2 days.

Comparative effects of different enzymatic hydrolysates of konjac glucomannan on gut flora and constipation in rats.

This study aimed to compare the effects of different hydrolysates (named GKOS and MKOS) on constipated rats, which were obtained by degradation from konjac glucomannan by β-glucanase and β-mannanase, respectively. GKOS and MKOS were characterized and administered by gavage at 100 mg kg to constipated rats. The variation of the gut flora, content of short-chain fatty acids (SCFAs), defecation function, gastrointestinal motility, and intestinal mucus secretion were determined to evaluate their regulatory effects on constipation.

Target identification and occupancy measurement of necrosis avid agent rhein using bioorthogonal chemistry-enabling probes.

Necrosis is an important biomarker, which only occurs in pathological situations. Tracking of necrosis avid agents is of crucial importance toward understanding their mechanisms. Herein, we developed a modular probe strategy based on bioorthogonal copper-free click chemistry.

Cyclocarya paliurus triterpenoids suppress hepatic gluconeogenesis via AMPK-mediated cAMP/PKA/CREB pathway.

Background: Abnormal enhancement of hepatic gluconeogenesis is a vital mechanism of the pathogenesis of Type 2 diabetes mellitus (T2DM); thus, its suppression may present an efficient therapeutic strategy for T2DM. Cyclocarya paliurus (CP), a plant species native to China, has been reported to have anti-hyperglycemia activity. Our previous studies have revealed that Cyclocarya paliurus triterpenic acids (CPT) exert the favorable glucose-lowering activity, but the regulatory effect of CPT on hepatic gluconeogenesis is still unclarified.

The role of exosomal CDC6 in the hirudin-mediated suppression of the malignant phenotype of bladder cancer cells.

Background: Bladder cancer is a malignant tumor characterized by high recurrence and persistence due to the limited therapies that are currently available. Hirudin exerts a strong anticancer effect on several tumors. Thus, it is urgent to explore the biological function of hirudin in bladder cancer and the role of bladder cancer-derived exosomes in tumor inhibition.

Development of Duramycin-Based Molecular Probes for Cell Death Imaging.

Cell death is involved in numerous pathological conditions such as cardiovascular disorders, ischemic stroke and organ transplant rejection, and plays a critical role in the treatment of cancer. Cell death imaging can serve as a noninvasive means to detect the severity of tissue damage, monitor the progression of diseases, and evaluate the effectiveness of treatments, which help to provide prognostic information and guide the formulation of individualized treatment plans. The high abundance of phosphatidylethanolamine (PE), which is predominantly confined to the inner leaflet of the lipid bilayer membrane in healthy mammalian cells, becomes exposed on the cell surface in the early stages of apoptosis or accessible to the extracellular milieu when the cell suffers from necrosis, thus representing an attractive target for cell death imaging.

Direct Cyclopropanation of Quinolinium Zwitterionic Thiolates via Dearomative Reactions.

A one-pot, two-step protocol for the synthesis of libraries of remarkable functionalized sulfone analogues of 9b,10,10a,10b-tetrahydro-1-cyclopropa[][1,4]thiazino[4,3-]quinolines is described. A class of various functionalized molecular skeletons was obtained by cyclopropanation of quinolinium zwitterionic thiolates. The reaction pathway involves the formation of a [2 + 1] cycloaddition intermediate followed by a [5 + 1] cycloaddition.

Functional variants of RPS6KB1 and PIK3R1 in the autophagy pathway genes and risk of bladder cancer.

Autophagy plays a critical role in cancer, since it can either suppress tumorigenesis by inhibiting cancer cell survival, or facilitate tumorigenesis by promoting cancer cell proliferation and tumor growth. However, the role of genetic variants of autophagy-regulated key genes for bladder cancer risk remained unclear. Here, we aimed to explore the association of bladder cancer with genetic variants on genes involved in autophagy pathway.

Comparative study of the laxative effects of konjac oligosaccharides and konjac glucomannan on loperamide-induced constipation in rats.

Dietary fiber is the basic therapeutic method to relieve the symptoms of chronic constipation. The aim of this study was to compare the laxative effect of konjac glucomannan (KGM) and konjac oligosaccharides (KOS) on constipated rats. KGM and KOS were administered to loperamide-induced constipated rats at dosages of 100 mg per kg bw and 400 mg per kg bw for 15 days.

Aloe vera mitigates dextran sulfate sodium-induced rat ulcerative colitis by potentiating colon mucus barrier.

Ethnopharmacological Relevance: Aloe vera (L.) Burm. f.

Combining combretastatin A4 phosphate with ginsenoside Rd synergistically inhibited hepatocellular carcinoma by reducing HIF-1α via PI3K/AKT/mTOR signalling pathway.

Objectives: Combretastatin A4 phosphate (CA4P), a vascular disrupting agent (VDA), can cause rapid tumour vessel occlusion. Subsequently, extensive necrosis is discovered in the tumour center, which induces widespread hypoxia and the rise of the α subunit of hypoxia-inducible factor-1 (HIF-1α). The aim of this study was to evaluate the inhibition of hepatocellular carcinoma growth by combining CA4P with HIF-1 α inhibitor and investigate the mechanism of this combination.

Pyrrolo[2,3-b]pyridine-3-one derivatives as novel fibroblast growth factor receptor 4 inhibitors for the treatment of hepatocellular carcinoma.

Aberrant signaling of the FGF/FGFR pathway occurs frequently in cancers and is an oncogenic driver in many solid tumors, especially liver cancer. With the resurgence of interest in irreversible inhibitors, efforts have been directed to the discovery of irreversible FGFR4 inhibitors. Currently, several selective irreversible inhibitors containing pyrrolo[2,3-b]pyridine-3-one and pyrrolo[2,3-d]pyrimidin-2-amine skeletons were designed and synthesized as FGFR4 inhibitors.

Untiring Pursuit for Glucarate-Based Molecular Imaging Probes.

Glucarate, a physiologic end-product of the D-glucuronic acid pathway in mammals, is a six-carbon dicarboxylic acid with a wide range of uses. Glucarate-based molecular imaging probes including [Tc]glucarate and [F]glucarate have been developed and demonstrated to have infarct/necrosis-avid and/or tumor-seeking properties, showing potential applications in early detection of myocardial infarction, evaluation of tissue viability, monitoring of therapeutic effectiveness, and noninvasive imaging of certain tumors including drug-resistant ones. The mechanism by which [Tc]glucarate localizes in acute necrotic tissues has been demonstrated to be largely attributable to its binding to the positively charged histones, which become accessible after the disruption of the cell and nuclear membranes as a result of irreversible damage, while the tumor-seeking mechanism of [Tc]glucarate has been found to be closely related to glucose transporter 5 expression.

Design and Evaluation of Rhein-Based MRI Contrast Agents for Visualization of Tumor Necrosis Induced by Combretastatin A-4 Disodium Phosphate.

Purpose: Visualization of tumor necrosis can determine tumor response to therapy. Our previous study showed that the rhein-based magnetic resonance imaging (MRI) contrast agent with alkane linker (GdL) could clearly image tumor necrosis. However, its water solubility and cell safety needed to be improved.

Laxative effect and mechanism of Tiantian Capsule on loperamide-induced constipation in rats.

Ethnopharmacological Relevance: Tiantian capsule (TTC), as a functional food, which consists of four herb medicines, including Aloe vera Burm.f. (25%), leaf juices, dried; Cucurbita moschata Duch.

A [3 + 2] cycloaddition/C-arylation of isatin ,'-cyclic azomethine imine 1,3-dipole with arynes.

A [3 + 2] annulation/C-arylation of isatin ,'-cyclic azomethine imine 1,3-dipole 1 with generated arynes has been established for the synthesis of 3,3-disubstituted oxindole scaffolds. These highly functionalized scaffolds were assembled in moderate yields (up to 85% yield). The novel spirooxindole scaffolds displayed moderate antitumor activities, which represented promising lead compounds for antitumor drug discovery.