MALT-1 shortens lifespan by inhibiting autophagy in the intestine of .

The caspase-like protease MALT1 promotes immune responses and oncogenesis in mammals by activating the transcription factor NF-κB. MALT1 is remarkably conserved from mammals to simple metazoans devoid of NF-κB homologs, like the nematode . To discover more ancient, NF-κB -independent MALT1 functions, we analysed the phenotype of upon silencing of MALT-1 expression systemically or in a tissue-specific manner.

Antiprotozoal activity of natural products from Nigerien plants used in folk medicine.

In the course of the screening of plants from Niger for antiprotozoal activity, the methanol extract of , and the dichloromethane extracts of and were found to be active against protozoan parasites, namely , , and/or . Myricitrin (), quercitrin () and 1-palmitoyl-lysolecithin () were isolated from . From , the three triterpene derivatives , , and are described here for the first time.

Resveratrol as a circadian clock modulator: mechanisms of action and therapeutic applications.

In the past decades, resveratrol has gained increasing attention due to its versatile and beneficial properties. This natural polyphenol, commonly present in the human diet, has been shown to induce SIRT1 and to modulate the circadian rhythm at the cellular and organismal levels. The circadian clock is a system regulating behavior and function of the human body, thus playing a crucial role in health maintenance.

Histone deacetylase-based dual targeted inhibition in multiple myeloma.

Despite enormous advances in terms of therapeutic strategies, multiple myeloma (MM) still remains an incurable disease with MM patients often becoming resistant to standard treatments. To date, multiple combined and targeted therapies have proven to be more beneficial compared to monotherapy approaches, leading to a decrease in drug resistance and an improvement in median overall survival in patients. Moreover, recent breakthroughs highlighted the relevant role of histone deacetylases (HDACs) in cancer treatment, including MM.

Antiproliferative activity of compounds isolated from the root bark of Lannea acida in multiple myeloma cell lines.

Lannea acida A. Rich. is a native plant of West Africa used in traditional medicine against diarrhea, dysentery, rheumatism, and women infertility.

Entinostat-Bortezomib Hybrids against Multiple Myeloma.

Although proteasome inhibitors have emerged as the therapeutic backbone of multiple myeloma treatment, patients often relapse and become drug refractory. The combination between proteasome and histone deacetylase inhibitors has shown to be more efficient compared to monotherapy by enhancing the anti-myeloma activity and improving the patient's lifetime expectancy. Hybrid molecules, combining two drugs/pharmacophores in a single molecular entity, offer improved effectiveness by modulating more than one target and circumventing differences in the pharmacokinetic and pharmacodynamic profiles, which are the main disadvantages of combination therapy.

Isolation and Structure Elucidation of Compounds from and Their Antiproliferative Activity against Multiple Myeloma Cells.

The phytochemical investigation of the dichloromethane root extract of led to the isolation of 18 compounds. Among these, compounds -, defined as 9-hydroxy-2,2-dimethyl-2-benzo[]chromene-5,10-dione 6--β-d-glucopyranoside (), (2,3)-3,4,7-trihydroxy-2-(3'-methylbut-2'-en-1'-yl)-2,3-dihydro-1-inden-1-one (), ()-2-(1',4'-dihydroxy-4'-methylpent-2'-en-1'-ylidene)-4,7-dihydroxy-1-indene-1,3(2)-dione (), ()-2,5,8-trihydroxy-3-(2'-hydroxy-3'-methylbut-3'-en-1'-yl)naphthalene-1,4-dione (), 6-hydroxy-3-(3'-methylbut-2'-en-1'-yl)-4-oxo-4-chromene-5-carboxylic acid (), and ()-2-(1'-hydroxy-4'-methylpent-3'-en-1'-yl)anthracene-9,10-dione (), respectively, have not yet been described. Their structures were elucidated based on spectroscopic data analysis, including IR, NMR, HRESIMS and ECD measurements.

Validation of a cell integrated next-generation impactor to assess in vitro drug transport of physiologically relevant aerosolised particles.

The development of novel inhaled formulations in the pre-clinical stage has been impeded by a lack of meaningful information related to drug dissolution and transport at the lung epithelia due to the absence of physiologically relevant in vitro respiratory models. The objective of the present study was to develop an in vitro experimental model, which combined the next generation impactor (NGI) and two respiratory epithelial cell lines, for examining the aerodynamic performance of dry powder inhalers and the fate of aerosolised drugs following lung deposition. The NGI impaction plates of stage 3 (i.

The Multiple Myeloma Landscape: Epigenetics and Non-Coding RNAs.

Despite advances in available treatments, multiple myeloma (MM) remains an incurable disease and represents a challenge in oncohematology. New insights into epigenetic factors contributing to MM development and progression have improved the knowledge surrounding its molecular basis. Beyond classical epigenetic factors, including methylation and acetylation, recent genome analyses have unveiled the importance of non-coding RNAs in MM pathogenesis.

Isolation and Structural Elucidation of Compounds from and Their In Vitro Antiprotozoal Activity.

Species of the genus are used in traditional medicine against fever and malaria. The present study focuses on the isolation and identification of bioactive compounds from extracts, and the evaluation of their antiprotozoal activity. Fractionation and isolation combined to LC-HRMS/MS-based dereplication provided 16 compounds: seven indole alkaloids, four indoline alkaloids, two secoiridoid glycosides, two iridoid glycosides, and one phenolic glucoside.

Phytochemical Investigation of the Roots of and Antiproliferative Activity of the Isolated Compounds against Multiple Myeloma Cells.

is a herbaceous plant belonging to the family Convolvulaceae and is native to tropical regions of Africa, America, and Asia. A dichloromethane root extract showed antiproliferative activity against multiple myeloma cells (RPMI 8226). The phytochemical investigation led to the isolation of 15 compounds.

Hygroline derivatives from Schizanthus tricolor and their anti-trypanosomatid and antiplasmodial activities.

Chemical investigation of the alkaloid extract of the aerial parts of Schizanthus tricolor led to the targeted isolation of 26 hygroline derivatives of which 20 were fully characterized. They have not yet been described in the literature and their structures were established by 1D and 2D NMR, UV and IR spectroscopy, and HRESIMS. The configuration was determined by Gauge-Independent Atomic Orbital NMR chemical shift calculations supported by the advanced statistical method DP4 plus, vibrational circular dichroism, and measurement of optical rotation.

Structure-Activity Relationships of Withanolides as Antiproliferative Agents for Multiple Myeloma: Comparison of Activity in 2D Models and a 3D Coculture Model.

Multiple myeloma (MM) is a hematological cancer in which relapse and resistance are highly frequent. Therefore, alternatives to conventional treatments are necessary. Withaferin A, a withanolide isolated from , has previously shown promising activity against various MM models.

Angiogenesis Is Differentially Modulated by Platelet-Derived Products.

Platelet-derived preparations are being used in clinic for their role in tissue repair and regenerative processes. The release of platelet-derived products such as autologous growth factors, cytokines and chemokines can trigger therapeutic angiogenesis. In this in vitro study, we evaluated and compared the ability of three platelet-derived preparations: platelet-rich-plasma (PRP), PRP-hyaluronic acid (PRP-HA) and platelet lysates (PL) at various concentrations (5-40%) to modulate human umbilical vein endothelial cells (HUVEC) biological effects on metabolism, viability, senescence, angiogenic factors secretion and angiogenic capacities in 2D (endothelial tube formation assay or EFTA) and in 3D (fibrin bead assay or FBA).

Pyridine-4(1)-one Alkaloids from as Antitrypanosomatid Agents.

Twelve new pyridine-4(1)-one derivatives, namely, 8-demethoxywaltherione F (), waltheriones R-V (, , , , and ), 1-methoxywaltherione O (), ()-15-hydroxywaltherione G (), (8)-8-hydroxywaltherione M (), (9,13)-2-hydroxymethylwaltherione C (), (9,10,13)-10-hydroxywaltherione C (), and ()-13-methoxywaltherione V (), as well as melovinone () and 5'-methoxywaltherione A () were isolated from the CHCl extract of the aerial parts of Their chemical structures were determined by means of a comprehensive analysis including H NMR, DEPTQ, HSQC, HMBC, H-H COSY, ROESY, and HRESIMS data. The absolute configurations were assigned via comparison of the experimental and calculated ECD data. In addition, the isolated constituents as well as the known waltheriones M-Q were evaluated for their in vitro antitrypanosomal activity.

Angiogenesis Analyzer for ImageJ - A comparative morphometric analysis of "Endothelial Tube Formation Assay" and "Fibrin Bead Assay".

Angiogenesis assays based on in vitro capillary-like growth of endothelial cells (EC) are widely used, either to evaluate the effect of anti- and pro-angiogenesis drugs of interest, or to test and compare the functional capacities of various types of EC and progenitor cells. Among the different methods applied to study angiogenesis, the most commonly used is the "Endothelial Tube Formation Assay" (ETFA). In suitable culture conditions, EC form two-dimensional (2D) branched structures that can lead to a meshed pseudo-capillary network.

Withanolide D Enhances Radiosensitivity of Human Cancer Cells by Inhibiting DNA Damage Non-homologous End Joining Repair Pathway.

Along with surgery and chemotherapy, radiation therapy (RT) is an important modality in cancer treatment, and the development of radiosensitizers is a current key challenge in radiobiology to maximize RT efficiency. In this study, the radiosensitizing effect of a natural compound from the withanolide family, withanolide D (WD), was assessed. Clonogenic assays showed that a 1 h WD pretreatment (0.

Anti-inflammatory and Quinone Reductase-Inducing Compounds from Beilschmiedia mannii.

Previous studies on the therapeutic potential of plant species found in the diet of chimpanzees living in Taï National Park have shown that they could be potential candidates for the search of new molecules useful for humans. Based on the screening of some of these plants, the fruits of , whose dichloromethane extract showed cancer chemopreventive properties, were selected. Bioactivity-guided fractionation of the extract resulted in the isolation and identification of two -pyrones, including desmethoxydihydromethysticin (1: ), found in a natural source for the first time, and a new congener, beilschmiediapyrone (2: ), as well as five known alkamides (3:  - 7: ).

Intranasal administration of resveratrol successfully prevents lung cancer in A/J mice.

Lung cancer is the most lethal cancer in the world. About 80% of lung cancer deaths are linked to tobacco use. As a complement to tobacco control, efficient chemoprevention strategies are needed to tackle lung cancer epidemic.

NF-κB and Angiogenesis Inhibitors from the Aerial Parts of Chresta martii.

The ethyl acetate extract of the aerial parts of Chresta martii showed significant in vitro NF-κB inhibition. Bioactivity-guided isolation was undertaken using HPLC microfractionation to localize the active compounds. Different zones of the HPLC chromatogram were linked to NF-κB inhibition.

HDAC inhibitors: a 2013-2017 patent survey.

Introduction: Zinc-dependent histone deacetylases (HDAC) inhibitors represent an important class of biologically active compounds with four of them approved by the FDA. A wide range of molecules has been reported for applications in several human diseases.

Areas Covered: This review covers recent efforts in the synthesis and applications of HDAC inhibitors from 2013-2017.

Carbazole-, Aspidofractinine-, and Aspidocarpamine-Type Alkaloids from Pleiocarpa pycnantha.

Three new alkaloids, janetinine (1a), pleiokomenine A (2), and huncaniterine B (3a), and 13 known compounds, pleiomutinine (3b), huncaniterine A (3c), 1-carbomethoxy-β-carboline (4), evoxanthine (5), deformyltalbotine acid lactone (6), pleiocarpamine (7), N-methyl-10-hydroxygeissoschizol (8), spegatrine (9), neosarpagine (10), aspidofractinine (11), N-methylkopsinin (12), pleiocarpine (13), and N-methylkopsinin- N-oxide (14), were isolated from the stem bark of Pleiocarpa pycnantha. Janetinine (1a) is a carbazole alkaloid; in pleiokomenine A (2), two aspidofractinine-type alkaloids are bridged by a methylene unit in an unprecedented way, and huncaniterine B (3a) is a pleiocarpamine-aspidofractinine-type dimer. The structures and relative configurations of these compounds were elucidated on the basis of NMR and MS analyses.

A Bivalent Role of Genistein in Sprouting Angiogenesis.

The effects of genistein on angiogenesis remain poorly understood. Some studies claim an antiangiogenic effect and others claim a pro-angiogenic one. Thus, the aim of this study was to determine if genistein may exhibit bivalent angiogenic effects.