The Natural Product Secoemestrin C Inhibits Colorectal Cancer Stem Cells via p38-S100A8 Feed-Forward Regulatory Loop.

Cancer stem cells (CSCs) are closely associated with tumor initiation, metastasis, chemoresistance, and recurrence, which represent some of the primary obstacles to cancer treatment. Targeting CSCs has become an important therapeutic approach to cancer care. Secoemestrin C (Sec C) is a natural compound with strong anti-tumor activity and low toxicity.

Anti-Tumor Potential of Post-Translational Modifications of PD-1.

Programmed cell death protein-1 (PD-1) is a vital immune checkpoint molecule. The location, stability, and protein-protein interaction of PD-1 are significantly influenced by post-translational modification (PTM) of proteins. The biological information of PD-1, including its gene and protein structures and the PD-1/PD-L1 signaling pathway, was briefly reviewed in this review.

Myofibrillogenesis Regulator-1 Regulates the Ubiquitin Lysosomal Pathway of Notch3 Intracellular Domain Through E3 Ubiquitin-Protein Ligase Itchy Homolog in the Metastasis of Non-Small Cell Lung Cancer.

Myofibrillogenesis regulator-1 (MR-1) is a multifunctional protein involved in the development of various human tumors. The study is the first to report the promoting effect of MR-1 on the development and metastasis of non-small cell lung cancer (NSCLC). MR-1 is upregulated in NSCLC and positively associated with poor prognosis.

Unexpected Noremestrin with a Sulfur-Bearing 15-Membered Macrocyclic Lactone from sp. 1454.

Two previous unreported epipolythiodioxopiperazines of the emestrin family, namely, noremestrin A () and secoemestrin E (), were successfully isolated from the fungal source sp. 1454. Employing comprehensive spectroscopic techniques, such as high-resolution electrospray ionization mass spectrometry, infrared, and nuclear magnetic resonance (NMR), along with NMR and electronic circular dichroism calculations, the chemical structures of compounds and were elucidated.

Miriplatin-loaded liposome, as a novel mitophagy inducer, suppresses pancreatic cancer proliferation through blocking POLG and TFAM-mediated mtDNA replication.

Pancreatic cancer is a more aggressive and refractory malignancy. Resistance and toxicity limit drug efficacy. Herein, we report a lower toxic and higher effective miriplatin (MPt)-loaded liposome, LMPt, exhibiting totally different anti-cancer mechanism from previously reported platinum agents.

The functions and regulatory pathways of S100A8/A9 and its receptors in cancers.

Inflammation primarily influences the initiation, progression, and deterioration of many human diseases, and immune cells are the principal forces that modulate the balance of inflammation by generating cytokines and chemokines to maintain physiological homeostasis or accelerate disease development. S100A8/A9, a heterodimer protein mainly generated by neutrophils, triggers many signal transduction pathways to mediate microtubule constitution and pathogen defense, as well as intricate procedures of cancer growth, metastasis, drug resistance, and prognosis. Its paired receptors, such as receptor for advanced glycation ends (RAGEs) and toll-like receptor 4 (TLR4), also have roles and effects within tumor cells, mainly involved with mitogen-activated protein kinases (MAPKs), NF-κB, phosphoinositide 3-kinase (PI3K)/Akt, mammalian target of rapamycin (mTOR) and protein kinase C (PKC) activation.

Enhanced binding of β-catenin and β-TrCP mediates LMPt's anti-CSCs activity in colorectal cancer.

Cancer stem cells (CSCs), a subpopulation of tumor cells with the features of self-renewal, tumor initiation, and insensitivity to common physical and chemical agents, are the key to cancer relapses, metastasis, and resistance. Accessible CSCs inhibitory strategies are primarily based on small molecule drugs, yet toxicity limits their application. Here, we report a liposome loaded with low toxicity and high effectiveness of miriplatin, lipo-miriplatin (LMPt) with high miriplatin loading, and robust stability, exhibiting a superior inhibitory effect on CSCs and non-CSCs.

A Mitochondrial Perspective on Noncommunicable Diseases.

Mitochondria are the center of energy metabolism in eukaryotic cells and play a central role in the metabolism of living organisms. Mitochondrial diseases characterized by defects in oxidative phosphorylation are the most common congenital diseases. Meanwhile, mitochondrial dysfunction caused by secondary factors such as non-inherited genetic mutations can affect normal physiological functions of human cells, induce apoptosis, and lead to the development of various diseases.

Cytotoxic hexadepsipeptides and anti-coronaviral 4-hydroxy-2-pyridones from an endophytic sp.

Three new hexadepsipeptides (-), along with beauvericin (), beauvericin D (), and four 4-hydroxy-2-pyridone derivatives (-) were isolated from the endophytic fungus sp. CPCC 400857 that derived from the stem of tea plant. Their structures were determined by extensive 1D and 2D NMR, and HRESIMS analyses.

Design, synthesis and biological evaluation of 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives as CDK inhibitors.

To explore the potential use of CDK inhibitors in pancreatic ductal adenocarcinoma (PDAC) therapy, a series of novel 2-((4-sulfamoylphenyl)amino)-pyrrolo[2,3-d]pyrimidine derivatives was designed, synthesised, and investigated for inhibition on both CDK kinase activity and cellular proliferation of pancreatic cancer. Most of new sulphonamide-containing derivatives demonstrated strong inhibitory activity on CDK9 and obvious anti-proliferative activity in cell culture. Moreover, two new compounds suppressed cell proliferation of multiple human pancreatic cancer cell lines.

Biomimetic Nanobomb for Synergistic Therapy with Inhibition of Cancer Stem Cells.

Cancer stem cells (CSCs), a type of cell with self-renewal, unlimited proliferation, and insensitivity to common physical and chemical factors, are the key to cancer metastasis, recurrence, and chemo-resistance. Available CSCs inhibition strategies are mainly based on small molecule drugs, yet are limited by their off-target toxicity. The link between CSCs and non-CSCs interconversion is difficult to sever.

New dimeric chromanone derivatives from the mutant strains of and their bioactivities.

Three new chromanone dimer derivatives, paecilins F-H (1-3) and ten known compounds (4-13), were obtained from the mutant strains of 114-2. Their structures were elucidated by extensive analysis of spectroscopic data and comparison with reported data, and the configurations of 1-3 were resolved by quantum chemical calculations of NMR shifts and ECD spectra. Compounds 5 and 11 showed significant anti-influenza A virus activities with IC values of 5.

Prenylemestrins A and B: Two Unexpected Epipolythiodioxopiperazines with a Thioethanothio Bridge from sp. Isolated by Genomic Analysis.

Prenylemestrins A and B ( and , respectively), two unusual epipolythiodioxopiperazines featuring a thioethanothio bridge instead of a polysulfide bridge, were isolated from the fungus sp. CPCC 400858 guided by genomic analysis. Their structures were determined by extensive spectroscopic data, NMR and ECD calculations, and X-ray diffraction analysis.

Metabolites from the plant endophytic fungus sp. CPCC 401423 and their cytotoxic activity against MIA PaCa-2 cells.

Twenty-two metabolites were isolated from sp. CPCC 401423 cultured on rice. The structures of all compounds were elucidated mainly by MS and NMR analysis as well as the necessary CD experimental evidence, of which penicillidione A (), penicillidione B (), ()-4-[(4-acetoxy-3-methyl-2-butenyl)oxy]phenylacetic acid (), ()-2-hydroxy-2-{4-[(3-methyl-2-butenyl)oxy]phenyl} (), ()-4-(2,3-dihydroxy-3-methyl-butoxy)phenylacetic acid (), ()-4-[(3-carboxy-2-butenyl)oxy]benzoic acid (), ()-4-[(4-hydroxy-3-methyl-2-butenyl)oxy]benzoic acid (), open-cycled N-demethylmelearoride A (), and penostatin M () were identified as new compounds.

Molecular Networking-Based Screening Led to the Discovery of a Cyclic Heptadepsipeptide from an Endolichenic sp.

MS/MS-based molecular networking strain prioritization led to the discovery of a group of cyclic depsipeptides from an endolichenic sp. The main component, xylaroamide A (), was obtained by LC-MS-guided isolation. The planar structure of compound was elucidated via 1D and 2D NMR, as well as MS/MS data.

ER-phagy in the Occurrence and Development of Cancer.

As an organelle, the endoplasmic reticulum (ER) is closely related to protein synthesis and modification. When physiological or pathological stimuli induce disorders of ER function, misfolded proteins trigger ER-phagy, which is beneficial for restoring cell homeostasis or promoting cell apoptosis. As a double-edged sword, ER-phagy actively participates in various stages of development and progression in tumor cells, regulating tumorigenesis and maintaining tumor cell homeostasis.

The novel ER stress inducer Sec C triggers apoptosis by sulfating ER cysteine residues and degrading YAP ER stress in pancreatic cancer cells.

Pancreatic adenocarcinoma (PAAD) is one of the most lethal malignancies. Although gemcitabine (GEM) is a standard treatment for PAAD, resistance limits its application and therapy. Secoemestrin C (Sec C) is a natural compound from the endophytic fungus , and its anticancer activity has not been investigated since it was isolated.

Role, molecular mechanism and the potential target of breast cancer stem cells in breast cancer development.

Breast cancer (BC) is one of the most common malignant tumors in women globally, and its occurrence has surpassed lung cancer and become the biggest threat for women. At present, breast cancer treatment includes surgical resection or postoperative chemotherapy and radiotherapy. However, tumor relapse and metastasis usually lead to current therapy failure thanks to breast cancer stem cells (BCSCs)-mediated tumorigenicity and drug resistance.

Microbial Transformation of -Clerodane Diterpenoid, Scutebarbatine F, by sp. CPCC 205437.

Biotransformation of the -clerodane diterpene, scutebarbatine F (), by sp. CPCC 205437 was investigated for the first time, which led to the isolation of nine new metabolites, scutebarbatine F-F (-). Their structures were determined by extensive high-resolution electrospray ionization mass spectrometry (HRESIMS) and NMR data analyses.

Endocytosis and Organelle Targeting of Nanomedicines in Cancer Therapy.

Nanomedicines (NMs) have played an increasing role in cancer therapy as carriers to efficiently deliver therapeutics into tumor cells. For this application, the uptake of NMs by tumor cells is usually a prerequisite to deliver the cargo to intracellular locations, which mainly relies on endocytosis. NMs can enter cells through a variety of endocytosis pathways.

Transcriptional co-activators YAP/TAZ: Potential therapeutic targets for metastatic breast cancer.

Breast cancer is the most commonly diagnosed cancer among women. Although routine and targeted therapies have improved the survival rate, there are still considerable challenges in the treatment of breast cancer. Metastasis is the leading cause of death in patients diagnosed with breast cancer.

Evaluation of antitumor efficacy of folate-poly(2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine based liposome.

This study aims to explore and evaluate the antitumor efficacy of doxorubicin (DOX)-loaded liposomes containing the novel tri-block polymer folate-poly (2-ethyl-2-oxazoline)-distearoyl phosphatidyl ethanolamine (F-PEOz-DSPE), compared with folate-polyethylene glycol-distearoyl phosphatidyl ethanolamine (F-PEG-DSPE) to offer an alternative for PEG decorated carriers. PEOz, a pH-sensitive polymer, exhibits similar solubility and segmental flexibility to PEG. In our previous study, PEOz was employed to an F-PEOz-DSPE which was segmentally similar to F-PEG-DSPE and exhibited selective targeting and pH-sensitivity in tumor cells.

The novel quinolizidine derivate IMB-HDC inhibits STAT5a phosphorylation at 694 and 780 and promotes DNA breakage and cell apoptosis via blocking STAT5a nuclear translocation.

Sophoridine is a quinolizidine natural product and the exploration of its derivatives has been carried out, and the potent anticancer compound IMB-HDC was acquired. Although previous studies have revealed that some sophoridine derivatives could induce DNA breakage, the underlying mechanisms of inhibition of DNA damage repair (ATR inactivation) and the apoptosis independent of p53, have not been elucidated. Our research reveals a novel DNA response mechanism different from general DNA-damaging agents, and that sophoridine derivate inhibits the phosphorylation of Tyr694 and Ser780 of STAT5a to induce the lessened shuttle from the cytoplasm to the nucleus, and leads to the decreased nuclear STAT5a and subsequently inhibits the expression of STAT5a target gene RAD51 that contributes to the checkpoint activation, thus inhibiting ATR activation.