-
BMC Complementary Medicine and Therapies May 2024Cepharanthin alone or in combination with glucocorticoid (GC) has been used to treat chronic immune thrombocytopenia (ITP) since the 1990s. Cepharanthine (CEP) is one of...
Cepharanthine synergistically promotes methylprednisolone pharmacodynamics against human peripheral blood mononuclear cells possibly via regulation of P-glycoprotein/glucocorticoid receptor translocation.
BACKGROUND
Cepharanthin alone or in combination with glucocorticoid (GC) has been used to treat chronic immune thrombocytopenia (ITP) since the 1990s. Cepharanthine (CEP) is one of the main active components of Cepharanthin. The purpose of this study was to investigate the effects of CEP on GC pharmacodynamics on immune cells and analyse the possible action mechanism of their interactions.
METHODS
Peripheral blood mononuclear cells (PBMCs), T lymphocytic leukemia MOLT-4 cells and daunorubicin resistant MOLT-4 cells (MOLT-4/DNR) were used to evaluate the pharmacodynamics and molecular mechanisms. Drug pharmacodynamics was evaluated by WST-8 assay. P-glycoprotein function was examined by rhodamine 123 assay. CD4CD25Foxp3 regulatory T cells and Th1/Th2/Th17 cytokines were detected by flow cytometry. P-glycoprotein expression and GC receptor translocation were examined by Western blot.
RESULTS
CEP synergistically increased methylprednisolone (MP) efficacy with the suppressive effect on the cell viability of PBMCs. 0.3 and 1 μM of CEP significantly inhibited P-glycoprotein efflux function of CD4 cells, CD8 cells, and lymphocytes (P<0.05). 0.03~3 μM of CEP also inhibited the P-glycoprotein efflux function in MOLT-4/DNR cells in a concentration-dependent manner (P<0.001). However, 0.03~3 μM of CEP did not influence P-glycoprotein expression. 0.03~0.3 μM of CEP significantly increased the GC receptor distribution from the cytoplasm to the nucleus in a concentration-dependent manner in MOLT-4/DNR cells. The combination did not influence the frequency of CD4, CD4CD25 and CD4CD25Foxp3 T cells or the secretion of Th1/Th2/Th17 cytokines from PBMCs. In contrast, CEP alone at 1 μM decreased the percentage of CD4 T cell significantly (P<0.01). It also inhibited the secretion of IL-6, IL-10, IL-17, TNF-α, and IFN-γ.
CONCLUSIONS
CEP synergistically promoted MP pharmacodynamics to decrease the cell viability of the mitogen-activated PBMCs, possibly via inhibiting P-glycoprotein function and potentiating GC receptor translocation. The present study provides new evidence of the therapeutic effect of Cepharanthin alone or in combination with GC for the management of chronic ITP.
Topics: Humans; Benzylisoquinolines; Leukocytes, Mononuclear; ATP Binding Cassette Transporter, Subfamily B, Member 1; Methylprednisolone; Receptors, Glucocorticoid; Drug Synergism; Benzodioxoles
PubMed: 38734604
DOI: 10.1186/s12906-024-04489-z -
Frontiers in Microbiology 2023The Chinese mitten crab () is a highly valued freshwater crustacean in China. While the natural shell color of is greenish brown (GH), we found a variety with a...
INTRODUCTION
The Chinese mitten crab () is a highly valued freshwater crustacean in China. While the natural shell color of is greenish brown (GH), we found a variety with a brownish-orange shell color (RH). Although RH is more expensive, it exhibits a lower molting frequency and growth rate compared with GH, which significantly reduces its yield and hinders large-scale farming. The growth and development of animals are closely related to their gut microbiota and gut tissue metabolic profiles.
METHODS
In this study, we compared the gut microbiome communities and metabolic profiles of juvenile RH and GH crabs using gene sequencing and liquid chromatography-mass spectrometry (LC-MS), respectively.
RESULTS
Our findings indicated that the intestinal microbial composition and metabolic characteristics of differed significantly between RH and GH. At the operational taxonomic unit (OTU) level, the α-diversity of the gut microbiota did not differ significantly between RH and GH, while the β-diversity of the RH gut microbiota was higher than that of the GH gut microbiota. At the species level, the richness of was significantly higher in the GH group, while the RH group had a significantly higher richness of three low-abundance species, , , and . In the current study, 598 gut tissue metabolites were identified, and 159 metabolites were significantly different between GH and RH. The metabolite profile of RH was characteristic of a low level of most amino acids and lipid metabolites and a high level of several pigments compared with that of GH. These metabolites were enriched in 102 KEGG pathways. Four pathways, including (1) Central carbon metabolism in cancer, (2) protein digestion and absorption, (3) alanine, aspartate and glutamate metabolism, and (4) aminoacyl-tRNA biosynthesis, were significantly enriched. The correlation analysis between metabolites and microbiotas indicated that most key differential metabolites were positively correlated with the abundance of _sp_MR-7.
DISCUSSION
This research provided a greater understanding of the physiological conditions of varieties with different shell colors by comparing the gut microbiota and gut tissue metabolome.
PubMed: 37520354
DOI: 10.3389/fmicb.2023.1218152 -
Phytochemistry Dec 2023Four undescribed bis-iridoid glycosides, named phukettosides A-D, and one iridoid glycoside, referred to as phukettoside E, were isolated and fully characterized from...
Four undescribed bis-iridoid glycosides, named phukettosides A-D, and one iridoid glycoside, referred to as phukettoside E, were isolated and fully characterized from the leaves of Morinda umbellata L. Phytochemical analysis also revealed the presence of eight known compounds. The structures were determined through extensive analysis of 1D and 2D-NMR spectroscopic and HRMS spectral data, and the absolute configurations of the isolates were deduced through ECD calculations. Biogenetic pathways for the bis-iridoid glycosides, phukettosides A-C, through intermolecular Diels-Alder type reactions, were proposed. The isolated compounds, with the exception of phukettosides B and D, were evaluated against a panel of cancer cell lines (MOLT-3, HuCCA-1, A549, HeLa, HepG2, and MDA-MB-231) and a non-cancerous cell line (MRC-5) for their cytotoxicity. None of the isolates had significant cytotoxic effects on the tested cell lines.
Topics: Humans; Iridoid Glycosides; Morinda; Glycosides; Plant Leaves; Iridoids; HeLa Cells
PubMed: 37852566
DOI: 10.1016/j.phytochem.2023.113890 -
General and Comparative Endocrinology Sep 2023A pair of Y-organs (YOs) synthesize ecdysteroids that initiate and coordinate molting processes in decapod crustaceans. The YO converts cholesterol to secreted products...
A pair of Y-organs (YOs) synthesize ecdysteroids that initiate and coordinate molting processes in decapod crustaceans. The YO converts cholesterol to secreted products through a biosynthetic pathway involving a Rieske oxygenase encoded by Neverland (Nvd) and cytochrome P450 monooxygenases encoded by Halloween genes Spook (Spo; Cyp307a1), Phantom (Phm; Cyp306a1), Disembodied (Dib; Cyp302a1), and Shadow (Sad; Cyp315a1). NAD kinase (NADK) and 5-aminolevulinic acid synthase (ALAS) support ecdysteroid synthesis in insects. A 20-hydroxylase, encoded by Shed in decapods and Shade in insects, converts ecdysone to the active hormone 20-hydroxyecdysone (20E). 20E is inactivated by cytochrome P450 26-hydroxylase (Cyp18a1). Contigs encoding these eight proteins were extracted from a Gecarcinus lateralis YO transcriptome and their expression was quantified by quantitative polymerase chain reaction. mRNA levels of Gl-Spo and Gl-Phm were four orders of magnitude higher in YO than those in nine other tissues, while mRNA levels of Gl-NADK and Gl-ALAS were similar in all ten tissues. In G. lateralis induced to molt by multiple leg autotomy, YO mRNA levels of Gl-Nvd, Gl-Spo, Gl-Phm, Gl-NADK, and Gl-ALAS were highest in intermolt and premolt stages and lower in postmolt. Gl-Dib mRNA level was not affected by molt stage. mRNA level of Gl-Sad, which converts 2-deoxyecdysone to ecdysone, was higher in mid- and late premolt stages, when YO ecdysteroidogenic capacity is greatest. Gl-Cyp18a1 mRNA level was highest in intermolt, decreased in premolt stages, and was lowest in postmolt. In animals induced to molt by eyestalk ablation, YO mRNA levels of all eight genes were not correlated with increased hemolymph 20E titers. These results suggest that YO ecdysteroidogenic genes are differentially regulated at transcriptional and translational levels.
Topics: Animals; Brachyura; Signal Transduction; Ecdysteroids; Molting; Ecdysone; RNA, Messenger
PubMed: 37127083
DOI: 10.1016/j.ygcen.2023.114304 -
International Journal of Molecular... Mar 2024T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive tumor mainly affecting children and adolescents. It is driven by multiple genetic mutations that together...
T-cell acute lymphoblastic leukemia (T-ALL) is an aggressive tumor mainly affecting children and adolescents. It is driven by multiple genetic mutations that together define the leukemic phenotype. Interestingly, based on genetic alterations and/or deregulated expression, at least six genetic subgroups have been recognized. The TAL/LMO subgroup is one of the most represented genetic subgroups, characterizing 30-45% of pediatric T-ALL cases. The study of lipid and metabolic profiles is increasingly recognized as a valuable tool for comprehending the development and progression of tumors. In this study, metabolic and lipidomic analysis via LC/MS have been carried out on four T-ALL cell lines belonging to the TAL/LMO subgroup (Jurkat, Molt-4, Molt-16, and CCRF-CEM) to identify new potential metabolic biomarkers and to provide a subclassification of T-ALL cell lines belonging to the same subgroup. A total of 343 metabolites were annotated, including 126 polar metabolites and 217 lipid molecules. The statistical analysis, for both metabolic and lipid profiles, shows significant differences and similarities among the four cell lines. The Molt-4 cell line is the most distant cell line and CCRF-CEM shows a high activity in specific pathways when compared to the other cell lines, while Molt-16 and Jurkat show a similar metabolic profile. Additionally, this study highlighted the pathways that differ in each cell line and the possible enzymes involved using bioinformatic tools, capable of predicting the pathways involved by studying the differences in the metabolic profiles. This experiment offers an approach to differentiate T-ALL cell lines and could open the way to verify and confirm the obtained results directly in patients.
Topics: Adolescent; Humans; Child; Precursor T-Cell Lymphoblastic Leukemia-Lymphoma; Metabolomics; Cell Line; Lipids; T-Lymphocytes
PubMed: 38612731
DOI: 10.3390/ijms25073921 -
Scientific Reports Oct 2023Plumage color has traditionally been regarded as a static ornamental trait, but evidence is accumulating for significant color changes without molt that typically reduce...
Plumage color has traditionally been regarded as a static ornamental trait, but evidence is accumulating for significant color changes without molt that typically reduce the conspicuousness of ornamentation. In some species, the social partner seems to increase its reproductive investment if the color trait is experimentally enhanced, suggesting that color change could act as a signal. However, the information content of this signal is so far unclear. For example, birds in poor condition or making greater effort may deteriorate more severely. We used brood size manipulations to alter the reproductive effort of male and female collared flycatchers Ficedula albicollis. Both sexes showed less severe decline in some reflectance attribute of their white breast when their brood was experimentally reduced. In each sex, greater deterioration of the reflectance trait affected by the manipulation was accompanied by increased feeding rate by the partner. These feeding patterns do not prove, but are consistent with, a compensatory response by the partner to induced degradation. The manipulation effects on color change we detected confirm for the first time that plumage color deterioration can indicate current reproductive effort, thereby providing a potential fitness advantage to social partners that react to such deterioration.
Topics: Animals; Female; Male; Songbirds; Passeriformes; Reproduction; Phenotype; Color; Feathers; Pigmentation
PubMed: 37907494
DOI: 10.1038/s41598-023-45348-0 -
Journal of Pesticide Science Aug 2023Derivatives of 1-benzyl-2-methylbenzimidazoles (BMBIs) were synthesized to evaluate their biological activities against , a lepidopteran model insect. Synthesized BMBIs...
Derivatives of 1-benzyl-2-methylbenzimidazoles (BMBIs) were synthesized to evaluate their biological activities against , a lepidopteran model insect. Synthesized BMBIs exhibited two different biological activities: inhibition of development and acute lethality. From a structural perspective, the activity varied with the position of the substitutions on the 1-benzyl moiety; BMBIs with substitutions on the 2 and/or 4 positions had comparatively high activity in comparison with those with substitutions on the 3-position. There was more activity for the inhibition of development with low doses, and more for acute lethality with high doses. The activity was also affected by the applied stage, that is, application in the 4th instar mostly interfered the larval molting or pupation, whereas that in the 3rd instar caused more acute mortality. Taken together, these results suggest that BMBIs have multiple modes of action.
PubMed: 37745173
DOI: 10.1584/jpestics.D23-010 -
Journal of Economic Entomology Oct 2023C-type lectins (CTLs) are an important family of pattern recognition receptors (PRRs) that regulate immune responses. The CTL5 gene of the silkworm Bombyx mori L....
C-type lectins (CTLs) are an important family of pattern recognition receptors (PRRs) that regulate immune responses. The CTL5 gene of the silkworm Bombyx mori L. (Lepidoptera: Bombycidae) encodes a protein comprised of 223 amino acids, containing a signal peptide and a carbohydrate recognition domain (CRD). Our previous study showed that CTL5 can facilitate the clearance of bacteria from larval hemocoel but the underlying mechanisms are unclear. In this study, we found that CTL5 was mainly expressed in fourth-instar larvae, adult moths, and the larval epidermis. CTL5 expression showed differential responses to both pathogenic stimuli and the molting hormone 20-hydroxyecdysone. The full-length (FL) and truncated (ΔN/ΔC/ΔNC) CTL5 recombinant proteins can bind to hemocytes, polysaccharides, bacteria, and spores of the entomopathogenic fungus Beauveria bassiana. Yeast 2-hybrid assays showed that the recombinant proteins can interact with integrin β2-β5 subunits. Recombinant proteins increased the phagocytic rate of hemocytes. Injection of recombinant CTL5 stimulated the expression of many immune genes in hemocytes, mainly antimicrobial peptides and immune signaling molecules. Additionally, transcriptomic sequencing of CTL5-stimulated hemocytes revealed 265 upregulated and 580 downregulated genes. Functional enrichment and the gene set enrichment analyses showed that differentially expressed genes were mainly enriched in innate immune responses and signaling. Our study suggests that CTL5 may act as an opsonin to enhance the clearance of pathogens by regulating both humoral and cellular responses.
PubMed: 37540584
DOI: 10.1093/jee/toad142 -
Marine Pollution Bulletin Jul 2024We exposed adult individuals of the sentinel mangrove crab Minuca rapax to waterborne microplastics (MP; 53-63 μm polyethylene spheres) in a long-term experiment...
We exposed adult individuals of the sentinel mangrove crab Minuca rapax to waterborne microplastics (MP; 53-63 μm polyethylene spheres) in a long-term experiment (56 days). Weassessed 1) MP effects on growth, survival, and food intake. and 2) the MP tissue acumulation and its reduction of body burden through feces and molting. MP exposure did not affect growth and survival. The hepatopancreas accumulated more MP than the gills and muscle. Most of the ingested MP particles were released in the feces and molts, indicating a rapid passage through the digestive tract. MP impaired food intake of M. rapax, with unknown consequences to the local populations. These results provide insights on MP translocation mechanisms, its elimination and toxicity associated with MP.
Topics: Animals; Brachyura; Water Pollutants, Chemical; Microplastics; Feces; Molting; Environmental Monitoring; Hepatopancreas
PubMed: 38688757
DOI: 10.1016/j.marpolbul.2024.116410 -
Life Sciences Jul 2023This study attempted to explore the mechanisms involved in pinostrobin (PN)-mediated acute leukemia cell apoptosis regulated by miR-410-5p.
AIMS
This study attempted to explore the mechanisms involved in pinostrobin (PN)-mediated acute leukemia cell apoptosis regulated by miR-410-5p.
MATERIAL AND METHODS
NB4 and MOLT-4 cells were cultured and treated with PN at the IC50 concentration. Apoptosis was examined by Annexin V-FITC/PI staining. RT-qPCR was used to measure the expression of caspase-3, BAK, BCL-W, and MCL-1. The target protein of PN was identified using LC-MS/MS followed by bioinformatic analysis. TargetScan, DIANA, and miRDB were used for the prediction of miRNAs involved in the PN-induced apoptosis mechanism. miRNA mimic transfection, RT-qPCR, and western blot analysis were performed to evaluate the regulatory effect of miRNA on its target and the involvement of miRNA in apoptosis induction by PN. In addition, the synergistic effect of PN and daunorubicin (DNR) were investigated by using the MTT assay.
KEY FINDINGS
The results showed that PN reduced cell viability and induced apoptosis in both leukemia cell lines. From the LC-MS/MS and bioinformatics analysis, SFRP5 and miR-410-5p were selected as a potential PN target protein and miRNA, respectively. After miRNA mimic transfection, miR-410-5p, which is an onco-miRNA, was decreased and led to increased apoptosis in both cell lines, indicating that this miRNA is involved in PN-mediated apoptosis mechanisms. Moreover, PN demonstrated a synergistic effect with DNR, suggesting that PN may be used in combination with conventional chemotherapy drugs.
SIGNIFICANCE
PN regulates the expression of miR-410-5p and SFRP5 to promote apoptosis in acute leukemia cells. It could be developed as an alternative treatment for leukemia in the future.
Topics: Humans; Chromatography, Liquid; Tandem Mass Spectrometry; Apoptosis; MicroRNAs; Leukemia, Myeloid, Acute; Daunorubicin; Cell Proliferation; Adaptor Proteins, Signal Transducing
PubMed: 37164308
DOI: 10.1016/j.lfs.2023.121739