The histone H3.3 K27M mutation suppresses Ser31phosphorylation and mitotic fidelity, which can directly drive gliomagenesis.

Serine 31 is a phospho-site unique to the histone H3.3 variant; mitotic phospho-Ser31 is restricted to pericentromeric heterochromatin, and disruption of phospho-Ser31 results in chromosome segregation defects and loss of p53-dependant G cell-cycle arrest. Ser31 is proximal to the H3.

Fyn-mediated phosphorylation of Menin disrupts telomere maintenance in stem cells.

Telomeres protect chromosome ends and determine the replication potential of dividing cells. The canonical telomere sequence TTAGGG is synthesized by telomerase holoenzyme, which maintains telomere length in proliferative stem cells. Although the core components of telomerase are well-defined, mechanisms of telomerase regulation are still under investigation.

Centromere defects, chromosome instability, and cGAS-STING activation in systemic sclerosis.

Centromere defects in Systemic Sclerosis (SSc) have remained unexplored despite the fact that many centromere proteins were discovered in patients with SSc. Here we report that lesion skin fibroblasts from SSc patients show marked alterations in centromeric DNA. SSc fibroblasts also show DNA damage, abnormal chromosome segregation, aneuploidy (only in diffuse cutaneous (dcSSc)) and micronuclei (in all types of SSc), some of which lose centromere identity while retaining centromere DNA sequences.

GSTO1 confers drug resistance in HCT‑116 colon cancer cells through an interaction with TNFαIP3/A20.

The aim of the present study was to decipher the mechanism of glutathione‑S‑transferase Ω‑1 (GSTO1)‑induced drug resistance in colon cancer cells. Cisplatin is used widely as a therapeutic drug in cancer, but colon cancer is the most susceptible to acquired drug resistance. Autophagy is recognized as one of the contributors to drug resistance in cancers.

Fumonisin B1 induces poly (ADP-ribose) (PAR) polymer-mediated cell death (parthanatos) in neuroblastoma.

Fumonisin B1 (FB1) is a well-known mycotoxin produced by Fusarium spp. and has a wide range of dose-dependent toxic effects, including nephrotoxicity, hepatotoxicity, and neurotoxicity. This research illustrated that FB1 exerts its toxicity in the neuroblastoma cell line through a distinct cell-death pathway called parthanatos.

GSK3β-Mediated Expression of CUG-Translated WT1 Is Critical for Tumor Progression.

The () gene is well known as a chameleon gene. It plays a role as a tumor suppressor in Wilms' tumor but also acts as an oncogene in other cancers. Previously, our group reported that a canonical AUG starting site for the WT1 protein (augWT1) acts as a tumor suppressor, whereas a CUG starting site for the WT1 protein (cugWT1) functions as an oncogene.

Immunosuppressive potential of astemizole against LPS activated T cell proliferation and cytokine secretion in RAW macrophages, zebrafish larvae and mouse splenocytes by modulating MAPK signaling pathway.

In this study, the immunomodulatory effects of astemizole (AST) against lipopolysaccharide (LPS) mediated T cell proliferation and induction of inflammation in RAW macrophages (in vitro), and zebrafish larvae (in vivo) were determined. AST significantly suppressed the phagocytic activity of macrophages (3.303 ± 0.

Vitexin induces apoptosis by suppressing autophagy in multi-drug resistant colorectal cancer cells.

Cancer treatment is limited due to the diverse multidrug resistance acquired by cancer cells and the collateral damage caused to adjacent normal cells by chemotherapy. The flavonoid compound vitexin exhibits anti-oxidative, anti-inflammatory and anti-tumor activity. This study elucidated the antitumor effects of vitexin and its underlying mechanisms in a multi-drug resistant human colon cancer cell line (HCT-116), which exhibits higher levels of multidrug-resistant protein 1 (MDR1) expression as compared with its parental cell line (HCT-116).

Vitexin confers HSF-1 mediated autophagic cell death by activating JNK and ApoL1 in colorectal carcinoma cells.

Heat shock transcription factor-1 (HSF-1) guards the cancerous cells proteome against the alterations in protein homeostasis generated by their hostile tumor microenvironment. Contrasting with the classical induction of heat shock proteins, the pro-oncogenic activities of HSF-1 remains to be explored. Therefore, cancer's fragile proteostatic pathway governed by HSF-1 could be a potential therapeutic target and novel biomarker by natural compounds.

Thymol Elicits HCT-116 Colorectal Carcinoma Cell Death Through Induction of Oxidative Stress.

Background: Colon cancer is one of the most deadly and common carcinomas occurring worldwide and there have been many attempts to treat this cancer. The present work was designed in order to evaluate thymol as a potent drug against colon cancer.

Materials And Methods: Cytotoxicity of thymol at different concentrations was evaluated against a human colon carcinoma cell line (HCT-116 cells).

Novel quercetin derivative TEF induces ER stress and mitochondria-mediated apoptosis in human colon cancer HCT-116 cells.

Although quercetin is very well known for its anticancer activity, however it shows some drawbacks. Herein, we have evaluated the apoptotic effect TEF (5, 3'-dihydroxy-3, 7, 4'-triethoxyflavone), a newly synthesized quercetin derivative on HCT-116 colon cancer cells. After 24h of treatment, the proliferation of colon cancer cells was inhibited by TEF.

5-Hydroxy-7-Methoxyflavone Triggers Mitochondrial-Associated Cell Death via Reactive Oxygen Species Signaling in Human Colon Carcinoma Cells.

Plant-derived compounds are an important source of clinically useful anti-cancer agents. Chrysin, a biologically active flavone found in many plants, has limited usage for cancer chemotherapeutics due to its poor oral bioavailability. 5-Hydroxy-7-methoxyflavone (HMF), an active natural chrysin derivative found in various plant sources, is known to modulate several biological activities.

Astemizole-Histamine induces Beclin-1-independent autophagy by targeting p53-dependent crosstalk between autophagy and apoptosis.

Apoptosis and autophagy are genetically regulated, evolutionarily conserved processes that can jointly seal cancer cell fates, and numerous death stimuli are capable of activating either pathway. Although crosstalk between apoptosis and autophagy is quite complex and sometimes contradictory, it remains a key factor determining the outcomes of death-related pathologies such as cancer. In the present study, exposure of MCF-7 breast cancer cells to HIS and the H1 receptor antagonist AST both alone and together with HIS (AST-HIS) led to generation of intracellular ROS, which induced massive cellular vacuolization through dilation of the ER and mitochondria.

Herbacetin Is a Novel Allosteric Inhibitor of Ornithine Decarboxylase with Antitumor Activity.

Ornithine decarboxylase (ODC) is a rate-limiting enzyme in the first step of polyamine biosynthesis that is associated with cell growth and tumor formation. Existing catalytic inhibitors of ODC have lacked efficacy in clinical testing or displayed unacceptable toxicity. In this study, we report the identification of an effective and nontoxic allosteric inhibitor of ODC.

Quercetin-3-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranoside suppresses melanin synthesis by augmenting p38 MAPK and CREB signaling pathways and subsequent cAMP down-regulation in murine melanoma cells.

In this study, the effect of purified quercetin-3-O-β-d-glucopyranosyl-(1 → 6)-β-d-glucopyranosid (QCGG) on melanogenesis was investigated. QCGG was isolated from the calyx of a traditional Korean medicinal herb, Persimmon (Diospyros kaki). The hypopigmentation effects of QCGG were determined by examination of cellular melanin contents, tyrosinase activity assay, cAMP assay, and Western blotting of α-MSH-stimulated B16F10 mouse melanoma cells.

Glutathione-S-transferase omega 1 (GSTO1-1) acts as mediator of signaling pathways involved in aflatoxin B1-induced apoptosis-autophagy crosstalk in macrophages.

Aflatoxin B1 (AFB1) is the most toxic aflatoxin species and has been shown to be associated with specific as well as non-specific immune responses. In the present study, using murine macrophage Raw 264.7 cells as a model, we report that short exposure (6h) to AFB1 caused an increase in the cellular calcium pool in mitochondria, which in turn elevated reactive oxygen species (ROS)-mediated oxidative stress and led to loss of mitochondrial membrane potential and ultimately c-Jun N-terminal kinases (JNK)-mediated caspase-dependent cell death.

Potential role of vitexin in alleviating heat stress-induced cytotoxicity: Regulatory effect of Hsp90 on ER stress-mediated autophagy.

Aims: Cells possess multiple methods for counteracting the deleterious consequences of stress induced by physical and chemical stimuli. Heat stress causes variations in the cellular environment, leading to cellular morbidity or mortality. Natural compounds that contain phenolic antioxidants, offer various therapeutic and biological activities.

Morin hydrate augments phagocytosis mechanism and inhibits LPS induced autophagic signaling in murine macrophage.

Morin, a natural flavonoid that is the primary bioactive constituent of the family Moraceae, has been found to be associated with many therapeutic properties. In this study, we evaluated the immunomodulatory activities of increasing concentration of morin hydrate in vitro. Three different concentrations of morin hydrate (5, 10, and 15μM) were used to evaluate their effect on splenocyte proliferation, phagocytic activity of macrophages, cytokine secretion and complement inhibition.

3,5,7,3',4'-pentamethoxyflavone, a quercetin derivative protects DNA from oxidative challenges: potential mechanism of action.

DNA protection is one of the most important strategies in cancer therapy. Since quercetin and its derivatives are found to be potent antioxidant agents, they are able to scavenge radicals significantly. Therefore, we focused on the DNA protection activity of 3,5,7,3',4'-pentamethoxyflavone (PMF), a quercetin derivative isolated from Kaemperia parviflora.

Potentiation of macrophage activity by thymol through augmenting phagocytosis.

The potent role of thymol, a natural compound, in modulation of macrophage activity was evaluated by determining all the sequential steps involved during phagocytosis. We found a significant increase in the proliferation of splenocytes in the presence of thymol and it proved to be a good mitogen. Uptake capacity of macrophages was enhanced due to increased membrane fluidity after treatment with thymol and it also increases lysosomal activity of macrophages.

Natural polyamine inhibits mouse skin inflammation and macrophage activation.

Objective: Natural polyamines are some of the most abundant polycationic molecules in eukaryotic cells, regulating gene expression. Polyamines have been reported to possess anti-inflammatory activities in many model inflammation systems. However, there is no report on their role in 12-O-tetradecanoylphorbol-13-acetate (TPA)-induced dermal edema.

Inhibition of inflammations and macrophage activation by ginsenoside-Re isolated from Korean ginseng (Panax ginseng C.A. Meyer).

This study was undertaken to evaluate the effect of ginsenoside-Re (Gin-Re) isolated from roots of Panax ginseng on carrageenan-induced paw and TPA-induced skin inflammations in experimental mice. Moreover, to confirm further the anti-inflammatory activities of Gin-Re, LPS-induced macrophage activation model was also used. Exposure of TPA on the ear of BALB/c mice caused a marked increase in both ear thickness and skin water content.

In vitro determination of the contraceptive spermicidal activity of essential oil of Trachyspermum ammi (L.) Sprague ex Turrill fruits.

This study was conducted to determine the spermicidal and contraceptive efficacy of essential oil of Trachyspermum ammi on human sperm in vitro. Chemical compositions of the oil were analyzed by GC-MS. Nearly 30 compounds representing 91.

alpha-Glucosidase inhibitory activities of 10-hydroxy-8(E)-octadecenoic acid: an intermediate of bioconversion of oleic acid to 7,10-dihydroxy-8(E)-octadecenoic acid.

Microbial conversion of unsaturated fatty acids often leads to special changes in their product structures and in biological potential. In our continuous effort to screen natural products for their antimicrobial and enzyme inhibitor activities, we found that 10-hydroxy-8(E)-octadecenoic acid (HOD) exhibited strong anti-alpha-glucosidase (EC 3.2.