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Asian Pacific Journal of Cancer... Jan 2024Up-regulation of the anti-apoptotic proteins such as Mcl-1 is associated with the primary and secondary resistance of tumor cells to ABT-737 Bcl-2 inhibitor. The...
INTRODUCTION
Up-regulation of the anti-apoptotic proteins such as Mcl-1 is associated with the primary and secondary resistance of tumor cells to ABT-737 Bcl-2 inhibitor. The combined treatment of Bcl-2 inhibitors with Mcl-1 inhibitors has been proposed as an attractive therapeutic strategy to overcome this drug resistance. Here, we investigated the effect of dihydroartemisinin on Mcl-1 expression and sensitization of T-ALL cells to ABT-737.
METHODS
The cell growth and survival were tested by the cell proliferation and MTT assays, respectively. The mRNA levels of Bcl-2, Mcl-1, Bax and P21 were examined by qRT-PCR. Apoptosis were detected by Hoechst 33342 staining and caspase-3 activity assay.
RESULTS
Our data showed that combination treatment with dihydroartemisinin and ABT-737 caused a significant decrease in the IC50 value and synergistically reduced the cell survival compared with dihydroartemisinin or ABT-737 alone. ABT-737 enhanced the Mcl-1 mRNA expression. Dihydroartemisinin also down-regulated the expression of Bcl-2 and Mcl-1 and enhanced the P21 and Bax expression. Moreover, dihydroartemisinin enhanced the apoptosis induced by ABT-737 in MOLT-4 and MOLT-17 cell lines.
CONCLUSION
In conclusion, dihydroartemisinin demonstrates anti-tumor activities in human ALL cells via inhibition of cell survival and growth. Dihydroartemisinin augments the apoptotic effect of ABT-737 by inhibiting the expression of Mcl-1.
Topics: Humans; Myeloid Cell Leukemia Sequence 1 Protein; bcl-2-Associated X Protein; Cell Line, Tumor; Proto-Oncogene Proteins c-bcl-2; Biphenyl Compounds; Antineoplastic Agents; Apoptosis; Precursor Cell Lymphoblastic Leukemia-Lymphoma; RNA, Messenger; Drug Synergism; Nitrophenols; Piperazines; Sulfonamides; Artemisinins
PubMed: 38285800
DOI: 10.31557/APJCP.2024.25.1.325 -
Cancer Science Apr 2024T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α-Pinene, a...
T-cell acute leukemia and lymphoma have a poor prognosis. Although new therapeutic agents have been developed, their therapeutic effects are suboptimal. α-Pinene, a monoterpene compound, has an antitumor effect on solid tumors; however, few comprehensive investigations have been conducted on its impact on hematologic malignancies. This report provides a comprehensive analysis of the potential benefits of using α-pinene as an antitumor agent for the treatment of T-cell tumors. We found that α-pinene inhibited the proliferation of hematologic malignancies, especially in T-cell tumor cell lines EL-4 and Molt-4, induced mitochondrial dysfunction and reactive oxygen species accumulation, and inhibited NF-κB p65 translocation into the nucleus, leading to robust apoptosis in EL-4 cells. Collectively, these findings suggest that α-pinene has potential as a therapeutic agent for T-cell malignancies, and further investigation is warranted.
Topics: Humans; NF-kappa B; T-Lymphocytes; Neoplasms; Apoptosis; Hematologic Neoplasms; Cell Line, Tumor; Cell Proliferation; Bicyclic Monoterpenes
PubMed: 38279512
DOI: 10.1111/cas.16086 -
Frontiers in Physiology 2023The crustacean hyperglycemic hormone (CHH) is a multifaceted neuropeptide instrumental in regulating carbohydrate and lipid metabolism, reproduction, osmoregulation,...
The crustacean hyperglycemic hormone (CHH) is a multifaceted neuropeptide instrumental in regulating carbohydrate and lipid metabolism, reproduction, osmoregulation, molting, and metamorphosis. Despite its significance, there is a dearth of research on its metabolic impact on the gills and epidermis-key organs in osmoregulation and molting processes. This study employed CHH dsRNA injections to silence CHH gene expression in followed by a metabolomic analysis of the gills and epidermis using nuclear magnetic resonance spectroscopy. Metabolic profiling through principal component analysis revealed the most pronounced changes at 24 h post-injection (hpi) in the epidermis and at 48 hpi in the gills. At 24 hpi, the epidermis exhibited significant modulation in 25 enrichment sets and 20 KEGG pathways, while at 48 hpi, 5 metabolite sets and 6 KEGG pathways were prominently regulated. Notably, pathways associated with amino acid metabolism, carbohydrate metabolism, and cofactor and vitamin metabolism were affected. A marked decrease in glucose and other carbohydrates suggested a compromised carbohydrate supply, whereas increased levels of citrate cycle intermediates implied a potential boost in energy provision. The silencing of CHH gene expression hampered the carbohydrate supply, which was possibly the main energy derived substrates. Conversely, the gills displayed significant alterations in 15 metabolite sets and 16 KEGG pathways at 48 hpi, with no significant changes at 24 hpi. These changes encompassed amino acid, carbohydrate, and lipid metabolism pathways. The decline in TCA cycle intermediates pointed to a potential downregulation of the cycle, whereas a decrease in ketone bodies indicated a shift towards lipid metabolism for energy production. Additionally, increased levels of nicotinate, nicotinamide, and quinolinate were observed in both organs. Overall, CHH's impact on the epidermis was prominent at 24 hpi and diminished thereafter, whereas its influence on metabolism in gills was delayed but intensified at 48 hpi. This differential CHH effect between gills and epidermis in provides new insights into the organ-specific regulatory mechanisms of CHH on energy metabolism and osmoregulation, warranting further comparative studies to elucidate the distinct roles of CHH in these organs.
PubMed: 38269063
DOI: 10.3389/fphys.2023.1349106 -
International Journal of Molecular... Jan 2024Cytochrome P450s (CYP450s) are a versatile superfamily of enzymes known to undergo rapid evolution. They have important roles across growth and development pathways in...
Cytochrome P450s (CYP450s) are a versatile superfamily of enzymes known to undergo rapid evolution. They have important roles across growth and development pathways in crustaceans, although it is difficult to characterise orthologs between species due to their sequence diversity. Conserved CYP450s enzymes in crustaceans are those associated with ecdysteroidogenesis: synthesising and breaking down the active moult hormone, 20-hydroxyecdysone. The complex life cycle of the ornate spiny lobster, , relies on moulting in order to grow and develop. Many of these diverse life stages have been analysed to establish a comprehensive transcriptomic database for this species. The transcripts putatively encoding for CYP450s were mapped using transcriptomic analysis and identified across growth and development stages. With the aid of phylogeny, 28 transcripts of 42 putative CYP450s were annotated, including the well conserved Halloween genes, which are involved in ecdysteroidogenesis. Expression patterns across the life stages determined that only a subset of the CYP450s can be detected in each life stage or tissue. Four transcripts show overlapping expression between metamorphosis and adult tissues, suggesting pleotropic functions of the multiple orthologs within .
Topics: Animals; Palinuridae; Cytochrome P-450 Enzyme System; Molting; Metamorphosis, Biological; Databases, Factual
PubMed: 38256143
DOI: 10.3390/ijms25021070 -
BioRxiv : the Preprint Server For... Dec 2023In , divergent Hedgehog-related (Hh-r) and Patched-related (PTR) proteins promote numerous processes ranging from epithelial and sense organ development to pathogen...
In , divergent Hedgehog-related (Hh-r) and Patched-related (PTR) proteins promote numerous processes ranging from epithelial and sense organ development to pathogen responses to cuticle shedding during the molt cycle. Here we show that Hh-r proteins are actual components of the cuticle and pre-cuticle apical extracellular matrices (aECMs) that coat, shape, and protect external epithelia. Different Hh-r proteins stably associate with the aECMs of specific tissues and with specific substructures such as furrows and alae. Hh-r mutations can disrupt matrix structure. These results provide a unifying model for the function of nematode Hh-r proteins and highlight ancient connections between Hh proteins and the extracellular matrix.
PubMed: 38234847
DOI: 10.1101/2023.12.26.573316 -
Molecular Biology and Evolution Feb 2024Speciation in the face of gene flow is usually associated with a heterogeneous genomic landscape of divergence in nascent species pairs. However, multiple factors, such...
Speciation in the face of gene flow is usually associated with a heterogeneous genomic landscape of divergence in nascent species pairs. However, multiple factors, such as divergent selection and local recombination rate variation, can influence the formation of these genomic islands. Examination of the genomic landscapes of species pairs that are still in the early stages of speciation provides an insight into this conundrum. In this study, population genomic analyses were undertaken using a wide range of sampling and whole-genome resequencing data from 96 unrelated individuals of Kentish plover (Charadrius alexandrinus) and white-faced plover (Charadrius dealbatus). We suggest that the two species exhibit varying levels of population admixture along the Chinese coast and on the Taiwan Island. Genome-wide analyses for introgression indicate that ancient introgression had occurred in Taiwan population, and gene flow is still ongoing in mainland coastal populations. Furthermore, we identified a few genomic regions with significant levels of interspecific differentiation and local recombination suppression, which contain several genes potentially associated with disease resistance, coloration, and regulation of plumage molting and thus may be relevant to the phenotypic and ecological divergence of the two nascent species. Overall, our findings suggest that divergent selection in low recombination regions may be a main force in shaping the genomic islands in two incipient shorebird species.
Topics: Humans; Genome-Wide Association Study; Genomic Islands; Genetic Speciation; Genome; Gene Flow; Recombination, Genetic; Selection, Genetic
PubMed: 38225175
DOI: 10.1093/molbev/msae006 -
Animals : An Open Access Journal From... Dec 2023The species composition of epibiotic communities on red king crab was investigated in Sayda Bay, Russia, during November of 2015 and 2016. The community consisted of 12...
The species composition of epibiotic communities on red king crab was investigated in Sayda Bay, Russia, during November of 2015 and 2016. The community consisted of 12 species in total. Among epibionts, the barnacle was most prevalent (67.0%), while the amphipod was the most frequent symbiont (77.3%). Infestation levels in May-June 2005 and September 2004 were higher, as a larger proportion of small crabs without fouling species were present during those seasons. The lower infestation intensities recorded for other common associated organisms during winter can be attributed to their increased mortality due to unfavorable temperature conditions. The localization of epibionts and symbionts were related to larval settlement patterns of attached species and feeding behavior of mobile species. Monthly growth increments for and were estimated at 2 mm in body length and 1.35 mm in basal diameter, respectively. Size-at-age data for epibionts can aid in the age determination of large male crabs that may skip an annual molt.
PubMed: 38200831
DOI: 10.3390/ani14010100 -
Communications Biology Jan 2024Southern elephant seals (SES) experience a 'catastrophic molt', a costly event characterized by the renewal of both hair and epidermis that requires high peripheral...
Southern elephant seals (SES) experience a 'catastrophic molt', a costly event characterized by the renewal of both hair and epidermis that requires high peripheral vascular circulation. Molting animals are therefore constrained by high metabolic heat loss and are thought to fast and remain on land. To examine the ability of individuals to balance the energetic constraints of molting on land we investigate the stomach temperature and movement patterns of molting female SES. We find that 79% of females swam and 61% ingested water or prey items, despite the cost of cold-water exposure while molting. This behavior was related to periods of warm and low wind conditions, and females that dived and ingested more often, lost less body mass. We conclude that the paradigm of fasting during the molt in this species, and the fitness consequences of this behavior should be reconsidered, especially in the context of a changing climate.
Topics: Female; Animals; Molting; Body Temperature Regulation; Seals, Earless; Water; Eating
PubMed: 38191678
DOI: 10.1038/s42003-023-05720-2 -
Journal of Genetics 2024In the fruit fly , circadian rhythm was disrupted when the inner nuclear membrane protein lamin B receptor (LBR) was depleted from its clock neurons ( 118, e2019756118....
In the fruit fly , circadian rhythm was disrupted when the inner nuclear membrane protein lamin B receptor (LBR) was depleted from its clock neurons ( 118, e2019756118. 2021; https://doi.org/10. 1073/pnas.2019756118 and 6, 0139, 2023; https://doi.org/10.34133/research.0139). Ordinarily, the clock proteinPERIOD (PER) forms foci close to the inner nuclear membrane in the circadian clock's repression phase. The size, number, and location of foci near the nuclear membrane oscillate with a 24-h rhythm. When LBR was absent the foci did not form. The PER foci bring and other clock genes close to the nuclear envelope, where their transcription is silenced. Then, in the circadian clock's activation phase, the PER protein gradually gets degraded and the foci disappear. The clock genes, including , relocate to the nucleus interior where they resume transcription. Rhythmic re-positioning of clock genes between nucleus periphery and interior, correlates with their repression and activation in the circadian cycle. Absence of LBR disrupted this rhythm. Phosphorylation of PER promoted the formation of foci whereas dephosphorylation by protein phosphatase 2A causedthem to disappear. LBR promoted focus formation by destabilizing the catalytic subunit of protein phosphatase 2A. The gene is no stranger to this journal. The first hint that vertebrate LBR is also a sterol biosynthesis enzyme, specifically, a sterol C14 reductase, was reported here (. 73, 33-41, 1994; https://www.ias.ac.in/article/fulltext/jgen/073/01/0033-0041). Mutations in the human gene cause a range of phenotypes--from the relatively benign Pelger-Huet anomaly to the perinatally lethal Greenberg skeletal dysplasia.Drosophila, like all insects, is a sterol auxotroph. The fly orthologue of vertebrate genes encodes a protein (dLBR) that shares several properties with vertebrate LBR proteins, with one notable exception. While human LBR complemented theyeast Saccharomyces cerevisiae erg24 mutant which lacks sterol C14 reductase activity, dLBR did not (, 2015-28, 2004; https://doi.org/10.1242/jcs.01052). Despite not possessing sterol reductase activity, dLBR retains significant sequence homology with vertebrate LBRs which have this activity. An undergraduate summer trainee in my laboratory obtained early (unpublished) evidence that dLBR lost sterol reductase activity during evolution. She transferred adult drosophila flies to vials containing a medium made of agar, dextrose, and dried and powdered mycelium of the filamentous fungus . On medium made with wild-type mycelium, theflies mated, laid eggs, hatched larvae, and developed pupae which eclosed progeny adult flies. The life cycle was no different than on 'regular' fly food composed of agar, dextrose and yeast extract. However, on a medium made with mycelium from a sterol C14 reductase null mutant, the flies laid eggs which hatched and released larvae, but the larvae failed to pupate, and no adult progeny flies emerged. This was because the fly lacks a sterol C14 reductase. The wild-type sterol, ergosterol, is a precursor of the steroid hormone ecdysone needed for molting and metamorphosis. Can expression of vertebrate LBR in dLBR-depleted fly clock neurons restore circadian rhythm? Can expression of vertebrate LBR enable flies to complete their life cycle on mutant medium? Does LBR regulate the vertebrate clock in a like manner? If yes, then is the sterol reductase activity dispensable in this role? These are some questions that came to my mind on a recent morning walk. The walk itself was a much-cherished outcome of my circadian clock.
Topics: Adult; Humans; Female; Animals; Agar; Drosophila melanogaster; Lamin B Receptor; Protein Phosphatase 2; Drosophila; Larva; Sterols; Glucose
PubMed: 38185834
DOI: No ID Found -
Insect Biochemistry and Molecular... Feb 2024Chitin is one of the most prevalent biomaterials in the natural world. The chitin matrix formation and turnover involve several enzymes for chitin synthesis, maturation,...
Chitin is one of the most prevalent biomaterials in the natural world. The chitin matrix formation and turnover involve several enzymes for chitin synthesis, maturation, and degradation. Sequencing of the Drosophila genome more than twenty years ago revealed that insect genomes contain a number of chitinases, but why insects need so many different chitinases was unclear. Here, we focus on insect GH18 family chitinases and discuss their participation in chitin matrix formation and degradation. We describe their variations in terms of temporal and spatial expression patterns, molecular function, and physiological consequences at chitinous cuticles. We further provide insight into the catalytic mechanisms by discussing chitinase protein domain structures, substrate binding, and enzymatic activities with respect to structural analysis of the enzymatic GH18 domain, substrate-binding cleft, and characteristic TIM-barrel structure.
Topics: Animals; Chitinases; Chitin; Phylogeny; Insecta; Genome, Insect; Biology
PubMed: 38184175
DOI: 10.1016/j.ibmb.2024.104071