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Methods in Molecular Biology (Clifton,... 2024Transcription factors (TFs) play a pivotal role as regulators of gene expression, orchestrating the formation and maintenance of diverse animal body plans and...
Transcription factors (TFs) play a pivotal role as regulators of gene expression, orchestrating the formation and maintenance of diverse animal body plans and innovations. However, the precise contributions of TFs and the underlying mechanisms driving the origin of basal metazoan body plans, particularly in ctenophores, remain elusive. Here, we present a comprehensive catalog of TFs in 2 ctenophore species, Pleurobrachia bachei and Mnemiopsis leidyi, revealing 428 and 418 TFs in their respective genomes. In contrast, morphologically simpler metazoans have a reduced TF representation compared to ctenophores, cnidarians, and bilaterians: the sponge Amphimedon encodes 277 TFs, and the placozoan Trichoplax adhaerens encodes 274 TFs. The emergence of complex ctenophore tissues and organs coincides with significant lineage-specific diversification of the zinc finger C2H2 (ZF-C2H2) and homeobox superfamilies of TFs. Notable, the lineages leading to Amphimedon and Trichoplax exhibit independent expansions of leucine zipper (BZIP) TFs. Some lineage-specific TFs may have evolved through the domestication of mobile elements, thereby supporting alternative mechanisms of parallel TF evolution and body plan diversification across the Metazoa.
Topics: Animals; Transcription Factors; Evolution, Molecular; Phylogeny; Ctenophora; Genome; Placozoa
PubMed: 38668980
DOI: 10.1007/978-1-0716-3642-8_20 -
Marine Drugs Apr 2024Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a...
Polyene macrolactams are a special group of natural products with great diversity, unique structural features, and a wide range of biological activities. Herein, a cryptic gene cluster for the biosynthesis of putative macrolactams was disclosed from a sponge-associated bacterium, sp. DSS69, by genome mining. Cloning and heterologous expression of the whole biosynthetic gene cluster led to the discovery of weddellamycin, a polyene macrolactam bearing a 23/5/6 ring skeleton. A negative regulator, WdlO, and two positive regulators, WdlA and WdlB, involved in the regulation of weddellamycin production were unraveled. The fermentation titer of weddellamycin was significantly improved by overexpression of and and deletion of . Notably, weddellamycin showed remarkable antibacterial activity against various Gram-positive bacteria including MRSA, with MIC values of 0.10-0.83 μg/mL, and antifungal activity against , with an MIC value of 3.33 μg/mL. Weddellamycin also displayed cytotoxicity against several cancer cell lines, with IC values ranging from 2.07 to 11.50 µM.
Topics: Streptomyces; Anti-Bacterial Agents; Humans; Lactams, Macrocyclic; Microbial Sensitivity Tests; Multigene Family; Polyenes; Candida albicans; Cell Line, Tumor; Antarctic Regions; Animals; Porifera; Antifungal Agents
PubMed: 38667806
DOI: 10.3390/md22040189 -
Marine Drugs Apr 2024Two new meroterpenoids, hyrtamide A () and hyrfarnediol A (), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester () and dictyoceratin C (), were...
Two new meroterpenoids, hyrtamide A () and hyrfarnediol A (), along with two known ones, 3-farnesyl-4-hydroxybenzoic acid methyl ester () and dictyoceratin C (), were isolated from a South China Sea sponge sp. Their structures were elucidated by NMR and MS data. Compounds - exhibited weak cytotoxicity against human colorectal cancer cells (HCT-116), showing IC values of 41.6, 45.0, and 37.3 μM, respectively. Furthermore, compounds and significantly suppressed the invasion of HCT-116 cells while also downregulating the expression of vascular endothelial growth factor receptor 1 (VEGFR-1) and vimentin proteins, which are key markers associated with angiogenesis and epithelial-mesenchymal transition (EMT). Our findings suggest that compounds and may exert their anti-invasive effects on tumor cells by inhibiting the expression of VEGFR-1 and impeding the process of EMT.
Topics: Humans; Animals; Antineoplastic Agents; Porifera; Colorectal Neoplasms; Terpenes; Epithelial-Mesenchymal Transition; HCT116 Cells; Vascular Endothelial Growth Factor Receptor-1; Vimentin; Cell Line, Tumor; China
PubMed: 38667800
DOI: 10.3390/md22040183 -
Marine Drugs Apr 2024In this study, Antarctic sponge-derived discorhabdin G was considered a hit for developing potential lead compounds acting as cholinesterase inhibitors. The hypothesis...
In this study, Antarctic sponge-derived discorhabdin G was considered a hit for developing potential lead compounds acting as cholinesterase inhibitors. The hypothesis on the pharmacophore moiety suggested through molecular docking allowed us to simplify the structure of the metabolite. ADME prediction and drug-likeness consideration provided valuable support in selecting 5-methyl-2H-benzo[h]imidazo[1,5,4-de]quinoxalin-7(3H)-one as a candidate molecule. It was synthesized in a four-step sequence starting from 2,3-dichloronaphthalene-1,4-dione and evaluated as an inhibitor of electric eel acetylcholinesterase (eeAChE), human recombinant AChE (hAChE), and horse serum butyrylcholinesterase (BChE), together with other analogs obtained by the same synthesis. The candidate molecule showed a slightly lower inhibitory potential against eeAChE but better inhibitory activity against hAChE than discorhabdin G, with a higher selectivity for AChEs than for BChE. It acted as a reversible competitive inhibitor, as previously observed for the natural alkaloid. The findings from the in vitro assay were relatively consistent with the data available from the AutoDock Vina and Protein-Ligand ANTSystem (PLANTS) calculations.
Topics: Cholinesterase Inhibitors; Animals; Molecular Docking Simulation; Acetylcholinesterase; Alkaloids; Butyrylcholinesterase; Humans; Electrophorus; Porifera; Structure-Activity Relationship; Horses
PubMed: 38667790
DOI: 10.3390/md22040173 -
Marine Drugs Apr 2024A new tetramic acid glycoside, aurantoside L (), was isolated from the sponge collected at Tsushima Is., Nagasaki Prefecture, Japan. The structure of aurantoside L ()...
A new tetramic acid glycoside, aurantoside L (), was isolated from the sponge collected at Tsushima Is., Nagasaki Prefecture, Japan. The structure of aurantoside L () composed of a tetramic acid bearing a chlorinated polyene system and a trisaccharide part was elucidated using spectral analysis. Aurantoside L () showed anti-parasitic activity against with an IC value of 0.74 µM.
Topics: Porifera; Animals; Glycosides; Leishmania; Antiprotozoal Agents; Pyrrolidinones; Japan; Inhibitory Concentration 50
PubMed: 38667788
DOI: 10.3390/md22040171 -
Marine Drugs Mar 2024Nicotine binds to nicotinic acetylcholine receptors (nAChRs) that are overexpressed in different cancer cells, promoting tumor growth and resistance to chemotherapy. In...
Nicotine binds to nicotinic acetylcholine receptors (nAChRs) that are overexpressed in different cancer cells, promoting tumor growth and resistance to chemotherapy. In this study, we aimed to investigate the potential of APS7-2 and APS8-2, synthetic analogs of a marine sponge toxin, to inhibit nicotine-mediated effects on A549 human lung cancer cells. Our electrophysiological measurements confirmed that APS7-2 and APS8-2 act as α7 nAChR antagonists. APS8-2 showed no cytotoxicity in A549 cells, while APS7-2 showed concentration-dependent cytotoxicity in A549 cells. The different cytotoxic responses of APS7-2 and APS8-2 emphasize the importance of the chemical structure in determining their cytotoxicity on cancer cells. Nicotine-mediated effects include increased cell viability and proliferation, elevated intracellular calcium levels, and reduced cisplatin-induced cytotoxicity and reactive oxygen species production (ROS) in A549 cells. These effects of nicotine were effectively attenuated by APS8-2, whereas APS7-2 was less effective. Our results suggest that APS8-2 is a promising new therapeutic agent in the chemotherapy of lung cancer.
Topics: Humans; alpha7 Nicotinic Acetylcholine Receptor; A549 Cells; Nicotine; Lung Neoplasms; Reactive Oxygen Species; Antineoplastic Agents; Cell Survival; Animals; Nicotinic Antagonists; Cell Proliferation; Cisplatin; Calcium; Porifera
PubMed: 38667764
DOI: 10.3390/md22040147 -
Marine Drugs Mar 2024Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing... (Review)
Review
Hypertension, a major health concern linked to heart disease and premature mortality, has prompted a search for alternative treatments due to side effects of existing medications. Sustainable harvesting of low-trophic marine organisms not only enhances food security but also provides a variety of bioactive molecules, including peptides. Despite comprising only a fraction of active natural compounds, peptides are ideal for drug development due to their size, stability, and resistance to degradation. Our review evaluates the anti-hypertensive properties of peptides and proteins derived from selected marine invertebrate phyla, examining the various methodologies used and their application in pharmaceuticals, supplements, and functional food. A considerable body of research exists on the anti-hypertensive effects of certain marine invertebrates, yet many species remain unexamined. The array of assessments methods, particularly for ACE inhibition, complicates the comparison of results. The dominance of in vitro and animal in vivo studies indicates a need for more clinical research in order to transition peptides into pharmaceuticals. Our findings lay the groundwork for further exploration of these promising marine invertebrates, emphasizing the need to balance scientific discovery and marine conservation for sustainable resource use.
Topics: Animals; Humans; Antihypertensive Agents; Aquatic Organisms; Biological Products; Dietary Supplements; Functional Food; Hypertension; Invertebrates; Peptides
PubMed: 38667757
DOI: 10.3390/md22040140 -
Journal of Natural Products Apr 2024Psammaplins are sulfur containing bromotyrosine alkaloids that have shown antitumor activity through the inhibition of class I histone deacetylases (HDACs). The...
Psammaplins are sulfur containing bromotyrosine alkaloids that have shown antitumor activity through the inhibition of class I histone deacetylases (HDACs). The cytotoxic properties of psammaplin A (), the parent compound, are related to peroxisome proliferator-activated receptor γ (PPARγ) activation, but the mechanism of action of its analogs psammaplin K () and bisaprasin () has not been elucidated. In this study, the protective effects against oxidative stress of compounds -, isolated from the sponge , were evaluated in SH-SY5Y cells. The compounds improved cell survival, recovered glutathione (GSH) content, and reduced reactive oxygen species (ROS) release at nanomolar concentrations. Psammaplins restored mitochondrial membrane potential by blocking mitochondrial permeability transition pore opening and reducing cyclophilin D expression. This effect was mediated by the capacity of - to activate PPARγ, enhancing gene expression of the antioxidant enzymes catalase, nuclear factor E2-related factor 2 (Nrf2), and glutathione peroxidase. Finally, HDAC3 activity was reduced by - under oxidative stress conditions. This work is the first description of the neuroprotective activity of at low concentrations and the mechanism of action of and . Moreover, it links for the first time the previously described effects of in HDAC3 and PPARγ signaling, opening a new research field for the therapeutic potential of this compound family.
Topics: PPAR gamma; Oxidative Stress; Humans; Animals; Molecular Structure; Reactive Oxygen Species; Neurons; Histone Deacetylases; NF-E2-Related Factor 2; Porifera; Membrane Potential, Mitochondrial; Antioxidants; Glutathione; Alkaloids; Catalase; Glutathione Peroxidase; Mitochondrial Membrane Transport Proteins; Disulfides; Tyrosine
PubMed: 38632902
DOI: 10.1021/acs.jnatprod.4c00153 -
PloS One 2024The giant honeybee Apis dorsata (Fabricius, 1793) is an evolutionarily ancient species that builds its nests in the open. The nest consists of a single honeycomb covered...
The giant honeybee Apis dorsata (Fabricius, 1793) is an evolutionarily ancient species that builds its nests in the open. The nest consists of a single honeycomb covered with the bee curtain which are several layers of worker bees that remain almost motionless with their heads up and abdomens down on the nest surface, except for the mouth area, the hub between inner- and outer-nest activities. A colony may change this semi-quiescence several times a day, depending on its reproductive state and ambient temperature, to enter the state of mass flight activity (MFA), in which nest organisation is restructured and defense ability is likely to be suppressed (predicted by the mass-flight-suspend-defensiveness hypothesis). For this study, three episode of MFA (mfa1-3) of a selected experimental nest were analysed in a case study with sequences of >60 000 images at 50 Hz, each comprise a short pre-MFA session, the MFA and the post-MFA phase of further 10 min. To test colony defensiveness under normative conditions, a dummy wasp was cyclically presented with a standardised motion programme (Pd) with intervening sessions without such a presentation (nPd). Motion activity at five selected surveillance zones (sz1-5) on the nest were analysed. In contrast to mfa1,2, in mfa3 the experimental regime started with the cyclic presentation of the dummy wasp only after the MFA had subsided. As a result, the MFA intensity in mfa3 was significantly lower than in mfa1-2, suggesting that a colony is able to perceive external threats during the MFA. Characteristic ripples appear in the motion profiles, which can be interpreted as a start signal for the transition to MFA. Because they are strongest in the mouth zone and shift to higher frequencies on their way to the nest periphery, it can be concluded that MFA starts earlier in the mouth zone than in the peripheral zones, also suggesting that the mouth zone is a control centre for the scheduling of MFA. In Pd phases of pre- and postMFA, the histogram-based motion spectra are biphasic, suggesting two cohorts in the process, one remaining at quiescence and the other involved in shimmering. Under MFA, nPd and Pd spectra were typically Gaussian, suggesting that the nest mates with a uniform workload shifted to higher motion activity. At the end of the MFA, the spectra shift back to the lower motion activities and the Pd spectra form a biphasic again. This happens a few minutes earlier in the peripheral zones than in the mouth zone. Using time profiles of the skewness of the Pd motion spectra, the mass-flight-suspend-defensiveness hypothesis is confirmed, whereby the inhibition of defense ability was found to increase progressively during the MFA. These sawtooth-like time profiles of skewness during MFA show that defense capability is recovered again quite quickly at the end of MFA. Finally, with the help of the Pd motion spectra, clear indications can be obtained that the giant honeybees engage in a decision in the sense of a tradeoff between MFA and collective defensiveness, especially in the regions in the periphery to the mouth zone.
Topics: Bees; Animals; Motion; Porifera; Wasps; Normal Distribution; Bedding and Linens
PubMed: 38630677
DOI: 10.1371/journal.pone.0298467 -
The Journal of Experimental Biology Apr 2024Filter-feeding demosponges are modular organisms that consist of modules each with one water-exit osculum. Once a mature module has been formed, the weight-specific...
Filter-feeding demosponges are modular organisms that consist of modules each with one water-exit osculum. Once a mature module has been formed, the weight-specific filtration and respiration rates do not change. Sponge modules only grow to a certain size and for a sponge to increase in size, new modules must be formed. However, the growth characteristics of a small single-osculum module sponge are fundamentally different from those of multi-modular sponges, and a theoretically derived volume-specific filtration rate scales as F/V=V-1/3, indicating a decrease with increasing total module volume (V, cm3). Here, we studied filtration rate (F, l h-1), respiration rate (R, ml O2 h-1), volume-specific (F/V) and weight-specific (F/W) filtration rates, and the ratios F/R and F/W along with growth rates of small single-osculum demosponge Halichondria panicea explants of various sizes exposed to various concentrations of algal cells. The following relationships were found: F/V=7.08V-0.24, F=a1W1.05, and R=a2W0.68 where W is the dry weight (mg). The F/R and F/W ratios were constant and essentially independent of W, and other data indicate exponential growth. It is concluded that the experimental data support the theoretical F/V∝V-1/3.
Topics: Animals; Water; Respiration; Filtration; Respiratory Rate; Porifera
PubMed: 38629316
DOI: 10.1242/jeb.247132