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Biology Letters Aug 2023Palaeoecological deductions are vital for understanding the evolution and diversification of species within prehistoric environments. This review highlights the... (Review)
Review
Palaeoecological deductions are vital for understanding the evolution and diversification of species within prehistoric environments. This review highlights the multitude of ways in which the microanatomy and microscopic structure of bones enables palaeoecological deductions. The occurrence of growth marks in bones is discussed, and their usefulness in deducing the ontogenetic status and age of individuals is considered, as well as how such marks in bones permit the assessment of the growth dynamics of individuals and species. Here osteohistology is shown to provide insight into the structure of past populations, as well as ecological relationships between individuals. In addition, the response of bones to trauma, disease and moulting is considered. Finally, I explore how osteohistology can give insight into ecomorphological adaptations, such as filter feeding, probe feeding and saltatorial locomotion. Methodological advances in three-dimensional microtomography and synchrotron scanning bodes well for future studies in osteohistology and despite some compromises in terms of tissue identity, circumvents the crucial issue of destructive analyses.
Topics: Humans; Locomotion; Molting
PubMed: 37607578
DOI: 10.1098/rsbl.2023.0245 -
European Journal of Medicinal Chemistry Oct 2023G to S phase transition 1 (GSPT1) is the requisite release factor for the translation termination. GSPT1 is identified as an oncogenic driver of several types of cancer...
G to S phase transition 1 (GSPT1) is the requisite release factor for the translation termination. GSPT1 is identified as an oncogenic driver of several types of cancer and considered to be a promising cancer therapeutic target. Although two selective GSPT1 degraders were advanced into clinical trials, neither of them has been approved for clinical use. Here we developed a series of new selective GSPT1 degraders, among which the optimal compound 9q potently induced degradation of GSPT1 with a DC of 35 nM in U937 cells, and showed good selectivity in the global proteomic profiling study. Mechanism studies revealed that compound 9q induced GSPT1 degradation through the ubiquitin-proteasome system. Consistent with its potent GSPT1 degradation activity, compound 9q displayed good antiproliferative activities against U937 cells, MOLT-4 cells, and MV4-11 cells, with IC values of 0.019 μM, 0.006 μM, and 0.027 μM, respectively. Compound 9q also dose-dependently induced G0/G1 phase arrest and apoptosis in U937 cells.
Topics: Lenalidomide; Peptide Termination Factors; Proteomics; Proteasome Endopeptidase Complex; Apoptosis
PubMed: 37418973
DOI: 10.1016/j.ejmech.2023.115580 -
Nanomedicine (London, England) May 2024Cancer is one of the leading causes of mortality worldwide, and its treatment faces several challenges. Phytoconstituents derived from recently discovered medicinal... (Review)
Review
Cancer is one of the leading causes of mortality worldwide, and its treatment faces several challenges. Phytoconstituents derived from recently discovered medicinal plants through nanotechnology potentially target cancer cells via PI3K/Akt/mTOR pathways and exert their effects selectively through the generation of reactive oxygen species through β-catenin inhibition, DNA damage, and increasing caspase 3/9 and p53 expression. These nanocarriers act specifically against different cancer cell lines such as HT-29, MOLT-4 human leukemia cancer and MCF-7 cell lines SKOV-3, Caov-3, SW-626, HepG2, A-549, HeLa, and MCF-7. This review comprehensively elaborates on the cellular and molecular mechanisms, and therapeutic prospects of various plant-mediated nanoformulations to attain a revolutionary shift in cancer immunotherapy.
PubMed: 38717427
DOI: 10.1080/17435889.2024.2343273 -
BioRxiv : the Preprint Server For... Sep 2023Uncovering the complexity of systems in non-model organisms is critical for understanding arthropod immunology. Prior efforts have mostly focused on Dipteran insects,...
Uncovering the complexity of systems in non-model organisms is critical for understanding arthropod immunology. Prior efforts have mostly focused on Dipteran insects, which only account for a subset of existing arthropod species in nature. Here, we describe immune cells or hemocytes from the clinically relevant tick using bulk and single cell RNA sequencing combined with depletion via clodronate liposomes, RNA interference, Clustered Regularly Interspaced Short Palindromic Repeats activation (CRISPRa) and RNA-fluorescence hybridization (FISH). We observe molecular alterations in hemocytes upon tick infestation of mammals and infection with either the Lyme disease spirochete or the rickettsial agent . We predict distinct hemocyte lineages and reveal clusters exhibiting defined signatures for immunity, metabolism, and proliferation during hematophagy. Furthermore, we perform a mechanistic characterization of two hemocyte markers: and . Depletion of phagocytic hemocytes affects and levels, which impacts blood feeding and molting behavior of ticks. Hemocytin specifically affects the c-Jun N-terminal kinase (JNK) signaling pathway, whereas astakine alters hemocyte proliferation in . Altogether, we uncover the heterogeneity and pleiotropic roles of hemocytes in ticks and provide a valuable resource for comparative biology in arthropods.
PubMed: 37693411
DOI: 10.1101/2023.08.31.555785 -
The Journal of Experimental Biology Jun 2024Organisms regularly adjust their physiology and energy balance in response to predictable seasonal environmental changes. Stressors and contaminants have the potential...
Organisms regularly adjust their physiology and energy balance in response to predictable seasonal environmental changes. Stressors and contaminants have the potential to disrupt these critical seasonal transitions. No studies have investigated how simultaneous exposure to methylmercury (MeHg) and food stress affects birds' physiological performance across seasons. We quantified several aspects of energetic performance in song sparrows, Melospiza melodia, exposed, or not, to unpredictable food stress and MeHg in a 2×2 experimental design, over 3 months of exposure during the breeding season, followed by 3 month post-exposure. Birds exposed to food stress had reduced basal metabolic rates and non-significant higher factorial metabolic scope during the exposure period, and had a greater increase in lean mass throughout most of the experimental period. Birds exposed to MeHg had increased molt duration, and increased mass.length-1 ratio of some of their primary feather. Birds exposed to the combined food stress and MeHg treatment often had responses similar to the stress-only or MeHg-only exposure groups, suggesting these treatments affected physiological performance through different mechanisms and resulted in compensatory or independent effects. Because the MeHg and stress variables were selected in candidate models with a delta AICc lower than two but the 95% CI of these variables overlapped zero, we found weak support for MeHg effects on all measures except BMR, and for food stress effects on MMR, factorial metabolic scope and feather mass.length-1 ratio. This suggests that MeHg and stress effects on these measures are statistically identified but not simple and/or were too weak to be detected via linear regression. Overall, combined exposure to ecologically relevant MeHg and unpredictable food stress during the breeding season does not appear to induce extra energetic costs for songbirds in the post-exposure period. However, MeHg effects on molt duration could carry-over across multiple annual cycle stages.
PubMed: 38856174
DOI: 10.1242/jeb.246239 -
Biomedicine & Pharmacotherapy =... Oct 2023The isoquinoline alkaloids found in Amaryllidaceae are attracting attention due to attributes that can be harnessed for the development of new drugs. The possible...
The isoquinoline alkaloids found in Amaryllidaceae are attracting attention due to attributes that can be harnessed for the development of new drugs. The possible molecular mechanisms by which montanine exerts its inhibitory effects against cancer cells have not been documented. In the present study, montanine, manthine and a series of 15 semisynthetic montanine analogues originating from the parent alkaloid montanine were screened at a single test dose of 10 μM to explore their cytotoxic activities against a panel of eight cancer cell lines and one non-cancer cell line. Among montanine and its analogues, montanine and its derivatives 12 and 14 showed the highest cytostatic activity in the initial single-dose screening. However, the native montanine exhibited the greatest antiproliferative activity against cancer cells, with a lower mean IC value of 1.39 µM, compared to the displayed mean IC values of 2.08 µM for 12 and 3.57 µM for 14. Montanine exhibited the most potent antiproliferative activity with IC values of 1.04 µM and 1.09 µM against Jurkat and A549 cell lines, respectively. We also evaluated montanine's cytotoxicity and cell death mechanisms. Our results revealed that montanine triggered apoptosis of MOLT-4 cells via caspase activation, mitochondrial depolarisation and Annexin V/PI double staining. The Western blot results of MOLT-4 cells showed that the protein levels of phosphorylated Chk1 Ser345 were upregulated with increased montanine concentrations. Our findings provide new insights into the mechanisms underlying the cytostatic, cytotoxic and pro-apoptotic activities of montanine alkaloids in lung adenocarcinoma A549 and leukemic MOLT-4 cancer cell types.
Topics: Humans; Cytostatic Agents; Amaryllidaceae Alkaloids; Antineoplastic Agents; Isoquinolines; Apoptosis; Alkaloids; Amaryllidaceae; Lung Neoplasms
PubMed: 37595426
DOI: 10.1016/j.biopha.2023.115295 -
Transplantation Proceedings Sep 2023Although mouse orthotopic liver transplantation (MOLT) is considered the gold standard in basic liver transplantation research, only a handful of transplantation...
BACKGROUND
Although mouse orthotopic liver transplantation (MOLT) is considered the gold standard in basic liver transplantation research, only a handful of transplantation research centers can establish the MOLT model reliably and reproducibly. Besides techniques and instruments, some nontechnical factors determine the outcomes of MOLT. This study aimed to investigate the influence of different bile duct stents and mouse strains on the long-term survival rate of MOLT.
METHODS
Varying donor-recipient-bile duct stent combinations were applied to groups 1-6 (G1, B6J-B6J-PP tube; G2, B6J-C3H-PP tube; G3, B6J-B6J-1.5XPE10 tube; G4, B6N-C3H-1.5XPE10 tube; G5, B10-C3H-1.5XPE10 tube; G6, B6N-C3H-1.25XPE10 tube) to value their effect on the long-term survival of MOLT. Liver transplantation was performed based on these experimental designs. The survival state was monitored for 3 months.
RESULTS
The 1-month survival rate of G1 and G2 was 14.3% and 70%, respectively. The 1-month survival rate of G3 was 80%, which had no significant difference compared with G2. Both G4 and G5 had a favorable 1-month survival rate of 100%. The 3-month survival rate of G3, G4, and G5 was 0%, 25%, and 80%, respectively. G6 had the same 1-month and 3-month survival rates as G5, which were 100% and 80%.
CONCLUSIONS
This study suggests that C3H mice were better recipient selections than B6J mice. Donor strains and stent materials are also important factors for the long-term survival of MOLT. An ideal long-term survival of MOLT could be achieved by a rational donor-recipient-stent combination.
Topics: Mice; Animals; Liver Transplantation; Mice, Inbred C3H; Bile Ducts; Stents
PubMed: 37419734
DOI: 10.1016/j.transproceed.2023.03.083 -
Current Protocols Oct 2023Trogocytosis is a process in which receptors on acceptor cells remove and internalize cognate ligands from donor cells. Trogocytosis has a profound and negative impact...
Trogocytosis is a process in which receptors on acceptor cells remove and internalize cognate ligands from donor cells. Trogocytosis has a profound and negative impact on mAb-based cancer immunotherapy, as seen in the treatment of chronic lymphocytic leukemia (CLL) with CD20 mAbs, such as rituximab (RTX) and ofatumumab (OFA). Our clinical observations of RTX/OFA-mediated loss of the CD20 target from circulating CLL cells have been replicated in our in vitro studies. Here we describe flow cytometry and fluorescence microscopy experiments, which demonstrate that acceptor cells, such as monocytes/macrophages that express FcγR, remove and internalize both antigen and donor cell-bound cognate IgG mAbs for several different mAb-donor cell pairs. Fluorescent mAbs and portions of the plasma cell membrane are transferred from donor cells to acceptor cells, which include the THP-1 monocytic cell line as well as freshly isolated monocytes. We describe rigorous controls to validate the reactions and eliminate dissociation or internalization as alternative mechanisms. Trogocytosis is likely to contribute to neutropenia, thrombocytopenia, and liver damage associated with use of antibody-drug conjugates. The methods we have described should allow for examination of strategies focused on blocking trogocytosis and its adverse effects. © 2023 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Trogocytosis of mAb-opsonized donor cells mediated by adherent THP-1 cells Alternate Protocol: Application of fluorescence microscopy to examine THP-1 cell-mediated trogocytosis Support Protocol 1: Alexa labeling of mAbs and determination of F/P ratios Support Protocol 2: Standard washing procedure Support Protocol 3: Labeling and opsonization of cells Basic Protocol 2: Trogocytosis mediated by human monocytes as acceptor cells Support Protocol 4: Isolation of human monocytes Basic Protocol 3: Trogocytosis mediated by THP-1 cells in solution Support Protocol 5: Retinoic acid treatment of THP-1 cells Support Protocol 6: Culturing of SCC-25, BT-474, MOLT-4 and THP-1 cell lines.
Topics: Humans; Leukemia, Lymphocytic, Chronic, B-Cell; Antibodies, Monoclonal, Murine-Derived; Trogocytosis; Antigens, CD20; Rituximab
PubMed: 37830752
DOI: 10.1002/cpz1.897 -
Comparative Biochemistry and... Oct 2023Crustacean molting is highly related to energy and lipid metabolism. This study was conducted to detect the changes of total lipids (TL), triacylglyceride (TAG),...
Crustacean molting is highly related to energy and lipid metabolism. This study was conducted to detect the changes of total lipids (TL), triacylglyceride (TAG), phospholipid (PL) and lipid droplets in hepatopancreas, and then to investigate the gene expression patterns related to hepatopancreatic lipid metabolism during the molting cycle of Chinese mitten crab Eriocheir sinensis. Hepatopancreatic TL and TAG increased significantly from post-molt stage to pre-molt stage, then decreased significantly from pre-molt stage to ecdysis stage, which is consistent to the changes of neutral lipid-rich adipocytes in hepatopancreas. By transcriptomic analysis, 65,325 transcripts were sequenced and assembled, and 28,033 transcripts were annotated. Most genes were related to energy metabolism, and the enriched genes were involved in carbohydrate and lipid metabolism and biosynthesis, especially in de novo synthesis of fatty acids and TAG, and ketone body production. Compared to the inter-molt stages, acetyl-CoA carboxylase, fatty acid synthase and other genes related to the synthesis of fatty acids were upregulated in the pre-molt stage. TAG synthesis related genes, including Glycerol-3-phosphate acyltransferase and 1-acylglycerol-3-phosphate acyltransferases, were upregulated in the post-molt stage compared to the inter-molt stage. The expression of ketone body-related genes had no significant changes during the molting cycle. Compared to the TAG synthetic pathway, ketone body biosynthesis may contribute less/secondarily to fatty acid metabolic processes, which could be involved in the other physiological processes or metabolism. In conclusion, these results showed that TAG is the major lipid deposition during inter- and pre-molt stages, and the most genes are related to the fatty acids and TAG metabolism in the hepatopancreas during the molting cycle of E. sinensis.
Topics: Animals; Transcriptome; Molting; Lipid Metabolism; Fatty Acids; Phosphates; Ketones; Brachyura; Hepatopancreas
PubMed: 37406959
DOI: 10.1016/j.cbpa.2023.111474 -
Nature Communications Mar 2024Uncovering the complexity of systems in non-model organisms is critical for understanding arthropod immunology. Prior efforts have mostly focused on Dipteran insects,...
Uncovering the complexity of systems in non-model organisms is critical for understanding arthropod immunology. Prior efforts have mostly focused on Dipteran insects, which only account for a subset of existing arthropod species in nature. Here we use and develop advanced techniques to describe immune cells (hemocytes) from the clinically relevant tick Ixodes scapularis at a single-cell resolution. We observe molecular alterations in hemocytes upon feeding and infection with either the Lyme disease spirochete Borrelia burgdorferi or the rickettsial agent Anaplasma phagocytophilum. We reveal hemocyte clusters exhibiting defined signatures related to immunity, metabolism, and proliferation. Depletion of phagocytic hemocytes affects hemocytin and astakine levels, two I. scapularis hemocyte markers, impacting blood-feeding, molting behavior, and bacterial acquisition. Mechanistically, astakine alters hemocyte proliferation, whereas hemocytin affects the c-Jun N-terminal kinase (JNK) signaling pathway in I. scapularis. Altogether, we discover a role for tick hemocytes in immunophysiology and provide a valuable resource for comparative biology in arthropods.
Topics: Animals; Hemocytes; Arthropods; Ixodes; Borrelia burgdorferi; Anaplasma phagocytophilum; Lyme Disease
PubMed: 38459063
DOI: 10.1038/s41467-024-46494-3