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Increased dietary intake of vitamin A promotes aortic valve calcification in vivo.

OBJECTIVE: Calcific aortic valve disease (CAVD) is a major public health problem with no effective treatment available other than surgery. We previously showed that mature heart valves calcify in response to retinoic acid (RA) treatment through downregulation of the SRY transcription factor Sox9. In this study, we investigated the effects of excess vitamin A and its metabolite RA on heart valve structure and function in vivo and examined the molecular mechanisms of RA signaling during the calcification process in vitro. METHODS AND RESULTS: Using a combination of approaches, we defined calcif

Redox activity associated with the maturation and capacitation of mammalian spermatozoa.

As rat spermatozoa undergo epididymal maturation, they acquire the ability to exhibit a spontaneous burst of luminol-peroxidase-dependent chemiluminescence when released into a simple, defined culture medium. This activity was suppressed by inhibitors of plasma membrane redox systems such as diphenylene iodonium, p-chloromercuribenzenesulfonic acid, and capsaicin, but was resistant to inhibition by resiniferatoxin and rotenone. The luminol-peroxidase signal was dependent on the presence of bicarbonate, enhanced by the substitution of fructose for glucose, and severely suppressed by desferoxami

Fat malabsorption in essential fatty acid-deficient mice is not due to impaired bile formation.

Essential fatty acid (EFA) deficiency induces fat malabsorption, but the pathophysiological mechanism is unknown. Bile salts (BS) and EFA-rich biliary phospholipids affect dietary fat solubilization and chylomicron formation, respectively. We investigated whether altered biliary BS and/or phospholipid secretion mediate EFA deficiency-induced fat malabsorption in mice. Free virus breed (FVB) mice received EFA-containing (EFA(+)) or EFA-deficient (EFA(-)) chow for 8 wk. Subsequently, fat absorption, bile flow, and bile composition were determined. Identical dietary experiments were performed in

Marine Natural Products as Potent Anticancer Agents (2020-2024): Structural Diversity, SARs and Target Prediction.

In recent years, Marine Natural Products (MNPs) have emerged as a significant source for anticancer drug discovery, as many natural products can offer structural diversity, unique mechanisms of action, and relatively low toxicity. This article provides a systematic review of MNPs with reported anticancer activities from 2020 to 2024. These compounds are classified into seven major categories: terpenoids, alkaloids, sterols, polyketides, peptides and proteins, polysaccharides, and macrolides. For each category, we elaborate on the marine sources, structural identification, in vitro anticancer a

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… Marine-Derived Terpenoids Marine-derived terpenoids are characterized by isoprene units as basic skeleton, and structurally cover multiple levels including monoterpenes, sesquiterpenes, diterpenes, triterpenes and higher terpenoids. … In 2022, Pedrosa’s research group isolated the brominated diterpene compound sphaerococcenol A ( 8 ) from the red alga Sphaerococcus coronopifolius Stackhouse 1797 ( Figure 7 ) [ 40 ]. …

Advanced Technologies for Large Scale Supply of Marine Drugs.

Marine organisms represent a source of unique chemical entities with valuable biomedical potentialities, broad diversity, and complexity. It is essential to ensure a reliable and sustainable supply of marine natural products (MNPs) for their translation into commercial drugs and other valuable products. From a structural point of view and with few exceptions, MNPs of pharmaceutical importance derive from the so-called secondary metabolism of marine organisms. When production strategies rely on marine macroorganisms, harvesting or culturing coupled with extraction procedures frequently remain t

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… In corals and their symbiotic algae, salicylic acid (SA) and its derivatives can induce the production of diterpenes and sterols. … These results suggest that SA may function as a general and somewhat selective diterpene-inducing signaling molecule in soft corals. …

Triptolide reverses hypoxia-induced epithelial-mesenchymal transition and stem-like features in pancreatic cancer by NF-κB downregulation.

Pancreatic ductal adenocarcinoma (PDA) is one of the most lethal malignancies characterized by an intense tumor stroma with hypoperfused regions, a significant inflammatory response and pronounced therapy resistance. New therapeutic agents are urgently needed. The plant-derived agent triptolide also known as "thunder god vine" has a long history in traditional Chinese medicine for treatment of rheumatoid arthritis and cancer and is now in a clinical phase II trial for establishing the efficacy against a placebo. The authors mimicked the situation in patient tumors by induction of hypoxia in ex

Serofendic acid prevents 6-hydroxydopamine-induced nigral neurodegeneration and drug-induced rotational asymmetry in hemi-parkinsonian rats.

Serofendic acid was recently identified as a neuroprotective factor from fetal calf serum. This study was designed to evaluate the neuroprotective effects of an intranigral microinjection of serofendic acid based on behavioral, neurochemical and histochemical studies in hemi-parkinsonian rats using 6-hydroxydopamine (6-OHDA). Rats were injected with 6-OHDA in the presence or absence of serofendic acid, or were treated with serofendic acid on the same lateral side, at 12, 24 or 72 h after 6-OHDA lesion. Intranigral injection of 6-OHDA alone induced a massive loss of tyrosine hydroxylase (TH)-im

Properties of Approved Antitumour Chinese Herbal Medicines: Integrating Evidence and Tradition.

The properties and meridian affinities of Chinese herbal medicine are closely associated with their therapeutic efficacy. This review focuses on approved antitumour Chinese medicines listed in the Pharmacopoeia of the People's Republic of China (2020 Edition, Volume I), highlighting their key components. Statistical methods were used to analyse the properties, flavours and channel tropisms of antitumour traditional Chinese medicine (TCM), including both proprietary formulations and commercially available individual herbs. Distinctive patterns were identified by comparing herb profiles with con

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… Concurrently, mangiferin induces G2/M phase cell-cycle arrest through downregulation of cyclin B1. 66 , 67 Terpenoids Terpenoids constitute a widespread class of bitter principles in TCM, structurally defined by isoprene units and classified into monoterpenes, sesquiterpenes, diterpenes, triterpenes … Mechanistically, oridonin increases the Bax/BCL-2 ratio to initiate apoptosis while simultaneously inhibiting mTORC1 activity, thereby eliciting antitumour responses. 69 Triptolide, a well-studied diterpene derived from Tripterygium wilfordii , suppresses overexpression of mouse double minute 2 homolog …

Marine-Derived Compounds: A New Horizon in Cancer, Renal, and Metabolic Disease Therapeutics.

Marine-derived compounds represent a rich source of structurally diverse molecules with therapeutic potential for cancer, renal disorders, metabolic-associated fatty liver disease (MAFLD), and atherosclerosis. This review systematically evaluates recent advances, highlighting compounds such as Microcolin H, Benzosceptrin C, S14, HN-001, Equisetin, glycosides (e.g., cucumarioside A2-2), ilimaquinone, and Aplidin (plitidepsin). Key mechanisms include autophagy modulation, immune checkpoint inhibition, anti-inflammatory effects, and mitochondrial homeostasis. Novel findings reveal glycosides' dua

Anticancer Potential of Farnesol Against Human Osteosarcoma Saos-2 Cells and Human Colorectal Carcinoma HCT-116 Cells.

IntroductionIncreased colorectal carcinoma (CRC) and osteosarcoma prevalence, low survival rate, poor prognosis, and the limitations of existing anticancer therapies like side effects of drugs, non-specificity, short half-life, etc., pose a need for novel anticancer drugs. Farnesol, an organic sesquiterpene compound, found in the essential oils of various plants has been shown to possess antioxidant, anti-inflammatory, and anticancer properties. However, the anticancer effect of farnesol against CRC and osteosarcoma has not yet been adequately elucidated.AimThe aim of the study was to analyze

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… The presence of components such as flavonoids, vinca alkaloids, diterpenes, sesquiterpenes, tannins, etc. in the plants is responsible for their anticancer activities [ 23 ]. …

Identification of the UBA2-WTIP fusion gene in acute myeloid leukemia.

Identifying and targeting oncogenic fusion genes have revolutionized the treatment of leukemia, such as PML-RARα fusion gene in acute promyelocytic leukemia. Here we identified an intrachromosomal fusion gene located on chromosome 19q.13 between UBA2 and WTIP gene in a case of acute myeloid leukemia. The UBA2-WTIP fusion gene contains the N-terminal E1_enzyme_family, VAE_Ubl domains of UBA2, and the C-terminal LIM domains of WTIP. The UBA2-WTIP fusion was detected by reverse transcriptase polymerase chain reaction and Sanger sequencing in 19 of 56 acute myeloid leukemia samples (33.9%). Ectopi

Zoledronic acid inhibits RANK expression and migration of osteoclast precursors during osteoclastogenesis.

Bisphosphonates have been known to directly inhibit bone resorption and promote apoptosis in mature osteoclasts. Although bisphosphonates have been recognized as the most effective drugs to treat osteoporosis and bone cancer metastasis, the exact effects and mechanism(s) of bisphosphonates on osteoclastogenesis are unclear. The aim of this study was to clarify whether nitrogen-containing bisphosphonates affect recruitment and differentiation in osteoclasts. We examined the effects of zoledronic acid on receptor activator of NF-κB (RANK) expression and cell migration during osteoclastogenesis i

P-Glycoprotein as a Therapeutic Target in Hematological Malignancies: A Challenge to Overcome.

P-glycoprotein (P-gp), a transmembrane efflux pump encoded by the ABCB1/MDR1 gene, is a major contributor to multidrug resistance in hematological malignancies. These malignancies, arising from hematopoietic precursors at various differentiation stages, can manifest in the bone marrow, circulate in the bloodstream, or infiltrate tissues. P-gp overexpression in malignant cells reduces the efficacy of chemotherapeutic agents by actively expelling them, decreasing intracellular drug concentrations, and promoting multidrug resistance, a significant obstacle to successful treatment. This review exa

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… Furthermore, the study by Reis et al. (2014) suggests that macrocyclic diterpenes, such as jolkinol D (a macrocyclic diterpene isolated from Euphorbia piscatoria ) and its derivatives could be valuable in resensitizing multidrug resistance phenotypes by targeting P-gp and other resistance mechanisms …

Proceedings of the CIMAGO Congress - Environment, Genetics and Oncobiology in the 21st Century - Challenges and Opportunities.

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… In response to the growing need for alternatives to chemotherapy, there is interest in exploring phytochemical antitumor agents like diterpenes, a biologically active group found in the genus Plectranthus L’Hér. … Following, we investigated the cytotoxic/antiproliferative profile of these diterpenes in urothelial carcinoma cells. Briefly, cell viability was evaluated by Alamar blue® assay, while cell death and the impact on cell cycle was assessed by flow cytometry. …

Totarol prevents neuronal injury in vitro and ameliorates brain ischemic stroke: Potential roles of Akt activation and HO-1 induction.

The natural product totarol, a phenolic diterpenoid and a major constituent isolated from the sap of Podocarpus totara, has been reported to have a potent antimicrobial activity. In this study, we determined whether totarol possessed an additional neuroprotective activity in vitro and in vivo. We found that totarol prevented glutamate- and oxygen and glucose deprivation-induced neuronal death in primary rat cerebellar granule neuronal cells and cerebral cortical neurons. Totarol increased Akt and GSK-3β phosphorylation, Nrf2 and heme oxygenase-1 (HO-1) protein expressions and suppressed oxidat

Genomic structure, chromosomal localization and expression profile of a novel melanoma differentiation associated (mda-7) gene with cancer specific growth suppressing and apoptosis inducing properties.

Abnormalities in cellular differentiation are frequent occurrences in human cancers. Treatment of human melanoma cells with recombinant fibroblast interferon (IFN-beta) and the protein kinase C activator mezerein (MEZ) results in an irreversible loss in growth potential, suppression of tumorigenic properties and induction of terminal cell differentiation. Subtraction hybridization identified melanoma differentiation associated gene-7 (mda-7), as a gene induced during these physiological changes in human melanoma cells. Ectopic expression of mda-7 by means of a replication defective adenovirus

The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy.

Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles publ

PSMA4 as a Druggable Target in Hidradenitis Suppurativa: Evidence From Mendelian Randomization and Single-Cell Transcriptomics.

Hidradenitis suppurativa (HS) is a chronic inflammatory skin disease with limited treatment options and frequent drug resistance. Novel therapeutic targets are urgently needed. We performed a druggable genome-wide Mendelian randomization (MR) analysis using blood cis-expression quantitative trait locus (eQTL) and HS genome-wide association study (GWAS) data. Colocalization, transcriptomic validation, single-cell RNA sequencing, and cell-cell communication analyses were integrated to explore gene function and cell-type specificity. We identified eight genes that showed significant associations

Oridonin in combination with imatinib exerts synergetic anti-leukemia effect in Ph+ acute lymphoblastic leukemia cells in vitro by inhibiting activation of LYN/mTOR signaling pathway.

Philadelphia chromosome-positive acute lymphoblastic leukemia (Ph+ ALL) is triggered by constitutively activated BCR-ABL and SRC family tyrosine kinases.They account for the activations of multiple growth-signaling pathways, including Raf/MEK/ERK, Akt/mTOR and STAT5 pathways. The BCR-ABL tyrosine kinase inhibitor imatinib is the standard treatment for Ph+ leukemia and plays efficacious role in CML. However, imatinib has few inhibitory effects on SRC tyrosine kinase with response rate of Ph+ ALL lower and relapse more frequent and quicker compared with CML. Previous studies showed that oridonin

Low dose triptolide reverses chemoresistance in adult acute lymphoblastic leukemia cells via reactive oxygen species generation and DNA damage response disruption.

BACKGROUND: Myasthenia gravis (MG) is an antibody-mediated autoimmune disease. In recent years, accumulating evidence has indicated that long non-coding RNAs (lncRNAs) can function as competing endogenous RNAs (ceRNAs), contributing to the progression of various autoimmune diseases. Nevertheless, the regulatory roles of ceRNAs in MG pathogenesis remain unclear. In this study, we aimed to elucidate the role of lncRNA OIP5-AS1 as a ceRNA associated with MG progression. METHODS: Real-time PCR was used to detect OIP5-AS1 levels in peripheral blood mononuclear cells (PBMCs) from patients with MG.