- |||||||||| doxycycline / Generic mfg.
Journal: Probing the Central Role of Phosphatidylinositol Synthesis in Lipid Metabolism of Eukaryotic Cells. (Pubmed Central) - May 14, 2022
To overcome this problem, we generated stable HEK293 cell lines in which a doxycycline (Dox)-inducible PIS-GFP transgene was stably integrated in a safe-harbor site of the genome and the endogenous PIS locus was inactivated via CRISPR/Cas9 genome editing...Current work focuses on the possibility that alternate source(s) of PI exist and on the question of what lipid synthetic pathways show adaptation to the greatly reduced or missing PIS activity. These experiments have the promise of a better understanding of how PI lipids determine the overall lipid landscape and homeostasis of eukaryotic cells and may unravel new molecular targets that can be exploited for therapeutic interventions in human metabolic and lipid disorders.
- |||||||||| doxycycline / Generic mfg.
Journal: Astrocyte-to-neuron reprogramming for spinal cord repair. (Pubmed Central) - May 14, 2022
Our initial experiments have begun exploring viral targeting of glial cells to promote doxycycline-inducible overexpression of neurogenic transcription factors (TFs) Ascl1 or a combination of microRNAs (miRs) miR124, miR9/9*, for neuronal conversion...Advances in cellular reprogramming are providing novel ways to manipulate the cytoarchitecture of the injured cervical spinal cord. Our ongoing work is now using this same approach to modify developing glial precursors that can be harness for their pro-reparative properties for spinal cord repair.
- |||||||||| doxycycline / Generic mfg.
Journal: Integrated redox sensitivity of vascular Kv1 channels. (Pubmed Central) - May 14, 2022
Arteries isolated from double transgenic mice with doxycycline-inducible increases in smooth muscle Kvβ1:Kvβ2 protein ratio exhibited a complete loss of L-lactate-induced enhancement of vasodilation to H O . Together, our results suggest that the Kvβ subunit complex in vascular smooth muscle may integrate multiple redox signals to enable tight control over Kv1 gating, vascular tone, and blood flow upon dynamic changes in metabolic demand.
- |||||||||| doxycycline / Generic mfg.
Journal: Myonuclei Can Replicate DNA. (Pubmed Central) - May 14, 2022
To test this hypothesis, we used the HSArtTA;Tet-O-H2B-GFP (HSA-H2B) mouse model, which uses doxycycline (DOX) treatment for temporal labeling (Tet-ON) of residential myonuclei...These data are the first to unambiguously demonstrate that myonuclei replicate DNA in vivo. The proposed project challenges current dogma and might significantly impact skeletal muscle treatment to maintain muscle mass with age and disease.
- |||||||||| doxycycline / Generic mfg.
Preclinical, Journal: The Role Lnc-RHL in Hepatic Cell Lineage Decisions and Proliferation in HepaRG Cells. (Pubmed Central) - May 14, 2022
We knocked down lnc-RHL expression with a doxycycline (Dox) inducible shRNA lentiviral vector in HepaRG cells to investigate the role of lnc-RHL...In addition, a key proliferation-associated transcription factor, FOXM1 was markedly upregulated after the loss of lnc-RHL. In summary, this study explores the role and expression of lnc-RHL in HepaRG cell differentiation and shows that it is required for the proper production of hepatocytes in these cells.
- |||||||||| doxycycline / Generic mfg., desmopressin / Generic mfg.
Preclinical, Journal: Genetic Deletion of the Prostaglandin EP4 Receptor in the Kidney Tubule of Adult Male Mice Has Mild Impact on Kidney Water Handling. (Pubmed Central) - May 14, 2022
To assess the tubular role of EP4 in adult mice we generated a mouse model with doxycycline-dependent deletion of EP4 along the renal tubule (Pax8Cre system) and assessed their renal phenotype regarding water handling...There were no differences between genotypes in their renal handling of water during water deprivation for 14 hours, or in their response to the vasopressin V2 receptor agonist dDAVP...In conclusion, EP4 in the renal tubule has a mild role in renal water handling. This new model provides a novel tool for assessing the role of EP4 in other aspects of kidney function or disease independently of potential developmental abnormalities or systemic effects.
- |||||||||| bortezomib / Generic mfg., doxycycline / Generic mfg.
THE DE NOVO DNA METHYLTRANSFERASE DNMT3B PLAYS AN IMPORTANT ROLE IN MM CELL GROWTH, CLONOGENICITY AND DRUG RESPONSE () - May 13, 2022 - Abstract #EHA2022EHA_1941;
DNMT3B specific targeting was achieved by using the DNMT3B specific inhibitor Nanaomycin A and genetic inhibition using doxycycline inducible shRNA against DNMT3B...Finally, combining Nanaomycin A (100 nM) with bortezomib (Bz, 4 nM) resulted in a significant decrease in colony formation compared to either Nanaomycin A or Bz treatment alone...DNMT3B targeting impairs MM cell proliferation and clonogenicity and sensitizes the cells to the proteasome inhibitor Bz. In the near future, the anti-myeloma activity of DNMT3B targeting will be validated in vivo using the 5TMM murine MM models and the underlying mechanisms will be further determined.
- |||||||||| doxycycline / Generic mfg., cytarabine / Generic mfg.
CELLULAR AND MOLECULAR MECHANISMS OF EVI1-EXPRESSING MLL-REARRANGED ACUTE MYELOID LEUKEMIA (Hall Stolz 1-2) - May 13, 2022 - Abstract #EHA2022EHA_757;
Background Expression of a doxycycline (DOX)-inducible acute myeloid leukaemia (AML)-associated iMLL-AF9 fusion transgene in long-term haematopoietic stem cells (LT-HSC) can lead to an invasive and chemo-resistant disease expressing the transcription factor EVI1...Evi1 expression also correlated with in vitro Ara-C resistance...Conclusion Our results suggest that expansion of Evi1-expressing HSPC by exogenous factors can result in a more aggressive MLL-AF9-driven AML. Ongoing data exploration and validation may characterize aberrantly expressed genes in TPO-stimulated Evi1 + iMLL-AF9-expressing HSPC as potential therapeutic targets to impair stemness of AML cells.
- |||||||||| doxycycline / Generic mfg.
INVESTIGATING GPR56 FUNCTION IN HUMAN IPSC-DERIVED HEMATOPOIETIC CELLS USING A TET-ON MODEL OF CONSTITUTIVE ACTIVATION () - May 13, 2022 - Abstract #EHA2022EHA_737;
This constitutively active GPR56 receptor form is overexpressed following doxycycline administration...These results are of interest in relation to normal HSC functions and may indicate the mechanisms through which overexpression of GPR56 (with increased activation) in LSCs contributes to poorer outcomes in AML. Future work will include identification and characterisation of the signalling pathways downstream of the GPR56 receptor to better understand this receptor’s role in the haematopoietic system in health and disease.
- |||||||||| NRAS MUTATIONS ARE INVOLVED IN ACUTE MYELOID LEUKAEMIA DRUG RESISTANCE () - May 13, 2022 - Abstract #EHA2022EHA_726;
Future work will use these cells to create a CRISPR-mediated reversion of the NRAS mutations which have arisen in the resistant cell lines, to better understand the role of NRAS mutations in FLT3-ITD+ AML. We will better characterise the impacts of a host of NRAS mutations within AML using over-expression and knockout cell lines, and assess drug sensitivity and subsequent pathway re-wiring.
- |||||||||| cephalexin / Generic mfg., doxycycline / Generic mfg.
Journal: 3D PCL/collagen nanofibrous medical dressing for one-time treatment of diabetic foot ulcers. (Pubmed Central) - May 12, 2022
In addition, the 3D nanofibrous dressing demonstrated good biocompatibility. It could significantly reduce the frequency of dressing changes and improve the healing of DFU wounds compared with the conventional multiple dressing changes method, suggesting a potential candidate for healing diabetic wounds.
- |||||||||| doxycycline / Generic mfg.
Interactome of HIV proteins and their host RNA interaction partners (Room 511/Channel 7) - May 12, 2022 - Abstract #AIDS2022AIDS_14;
This unique and comprehensive dataset of HIV protein ' human RNA interactions broadens our understanding on how HIV manipulates the RNA component of the host's cellular machinery during the course of infection and to establish and maintain latency. This information will support the search for latency reversing agents for a potent shock-and-kill strategy.
- |||||||||| doxycycline / Generic mfg., erythromycin / Generic mfg.
Journal: Valorisation of the diterpene podocarpic acid - Antibiotic and antibiotic enhancing activities of polyamine conjugates. (Pubmed Central) - May 12, 2022
However, in the presence of sub-therapeutic amounts of either doxycycline (4.5 µM) or erythromycin (2.7 μM) several analogues were observed to exhibit weak to modest antibiotic adjuvant properties against Pseudomonas aeruginosa and/or Escherichia coli. The observation of strong cytotoxicity and/or hemolytic properties for subsets of the library, in particular those analogues bearing methyl ester or n-pentylamide functionality, highlighted the fine balance of structural requirements and lipophilicity for antimicrobial activity as opposed to mammalian cell toxicity.
- |||||||||| doxycycline / Generic mfg.
Journal, Epigenetic controller: HIV Tat and cocaine interactively alter genome-wide DNA methylation and gene expression and exacerbate learning and memory impairments. (Pubmed Central) - May 12, 2022
In this study, we show that cocaine exposure worsens the learning and memory of doxycycline-inducible and brain-specific HIV Tat transgenic mice (iTat) and results in 14,838 hypermethylated CpG-related differentially methylated regions (DMRs) and 15,800 hypomethylated CpG-related DMRs, which are linked to 52 down- and 127 upregulated genes, respectively, in the hippocampus of iTat mice...We also find that sex (female) and age additively worsen the behavioral and pathological changes. These findings together indicate that chronic cocaine and long-term Tat expression interactively contribute to HAND, likely involving changes of DNA methylation and ECM receptor-ligand interactions.
- |||||||||| doxycycline / Generic mfg.
Journal: Systematic identification of ALK substrates by integrated phosphoproteome and interactome analysis. (Pubmed Central) - May 12, 2022
Thirty-seven ALK substrate candidates, including 34 phosphorylation sites not annotated in the PhosphoSitePlus database, were identified by integrated analysis of the phosphoproteome and crosslinking interactome of HEK 293 cells with doxycycline-induced ALK overexpression...Finally, using phosphoproteomic data from ALK mutant cell lines and patient-derived cells treated with ALK inhibitors, we found that the prediction of ALK activity was improved when the KSRs identified in this study were used instead of the public KSR dataset. Our approach is applicable to other kinases, and future identification of KSRs will facilitate more accurate estimations of kinase activity and elucidation of phosphorylation signals.
- |||||||||| doxycycline / Generic mfg.
Journal: Telomerase Reverse Transcriptase Expression Marks a Population of Rare Adipose Tissue Stem Cells. (Pubmed Central) - May 12, 2022
Here, we used a doxycycline-inducible mouse model to perform longitudinal, live-animal lineage-tracing of mTert-expressing cells for more than 1 year...Finally, we demonstrate that high-fat diet (HFD) can initiate differentiation of these cells in vivo. These data identify a population of adipose stem cells that contribute to the depot-specific response to HFD.
- |||||||||| doxycycline / Generic mfg.
Preclinical, Journal: Impact of Factors Secreted by Tumor Cells on Response of Pleural Mesothelial Cells to Different Sclerosing Agents in an In Vitro Model. (Pubmed Central) - May 12, 2022
MATERIAL AND METHODS The study used mesothelial cell (MeT-5A) cultures stimulated with sclerosing agents (talc, doxycycline, iodopovidone, and TGF-ß for 24 h) in the presence or absence of supernatants from adenocarcinoma cultures (HCC827)...CONCLUSIONS An addition of soluble factors produced by adenocarcinoma altered the inflammatory response of the pleural mesothelial cells after stimulation with sclerosing agents. Our observations suggest that the tumor paracrine effect affects biological pathways of pleurodesis.
- |||||||||| doxycycline / Generic mfg.
Identification of new therapeutic targets for hepatic regenerative medicine in Non-Alcoholic Fatty Liver Disease (NAFLD) (Meeting Point 3) - May 12, 2022 - Abstract #EASLILC2022EASL_ILC_2021;
Following diet treatment for 8-weeks, doxycycline was added to induce shRNA expression enabling gene knockdown, along-with western diet for another 16 weeks... RNAi-based functional genetic screen in combination with high-throughput sequencing will allow the identification of new gene targets and uncover new insights underlying NAFLD development and disease progression.
- |||||||||| doxycycline / Generic mfg.
Journal: Response to article by Sharma et al. (Pubmed Central) - May 11, 2022
RNAi-based functional genetic screen in combination with high-throughput sequencing will allow the identification of new gene targets and uncover new insights underlying NAFLD development and disease progression. No abstract available
- |||||||||| Thymoglobulin (anti-thymocyte globulin (rabbit)) / Sanofi
Preclinical, Journal: Rapamycin Treatment Is Beneficial for the Generation of Rabbit-Induced Pluripotent Stem-Like Cells. (Pubmed Central) - May 10, 2022
The expression of autophagy-related genes (ATG), ATG5, ATG7, LC3, and ULK1 was increased with different patterns during the induction process, expression of OCT4, SOX2, and KLF4 significantly increased (p < 0.05). The mentioned results indicate that rapamycin treatment is beneficial for the generation of rabbit iPSCs by regulating autophagy and pluripotency-related gene expression.
- |||||||||| triamcinolone acetonide topical / Generic mfg., doxycycline / Generic mfg.
Journal: Prurigo pigmentosa in a patient with newly diagnosed type one diabetes with diabetic ketoacidosis. (Pubmed Central) - May 9, 2022
Histopathological findings consistent with the clinical findings suggested the diagnosis of prurigo pigmentosa. After treatment with topical triamcinolone and oral doxycycline along with resolution of his ketosis after insulin administration, the patient's rash healed with reticulate hyperpigmentation.
- |||||||||| ampicillin / Generic mfg., doxycycline / Generic mfg., tetracycline / Generic mfg.
Journal: Cross-Sectional Survey of Prophylactic and Metaphylactic Antimicrobial Use in Layer Poultry Farming in Cameroon: A Quantitative Pilot Study. (Pubmed Central) - May 7, 2022
Tetracycline, sulfonamides, quinolones, and β-lactams (aminopenicillins) were the most sold and used drugs in layer farms...Doxycycline, sulfonamide, ampicillin, and streptomycin, which have been banned for layer poultry in the production of eggs for human consumption, were still used in Cameroon...This study highlights an irrational antimicrobial usage in layer poultry farms. Regulation of the use of antimicrobials and the education of farmers on adequate antimicrobial use are essential to preserve the effectiveness of drugs in both humans and animals.
- |||||||||| doxycycline / Generic mfg.
Biomarker, Journal, Tumor microenvironment: Low serum mesothelin in pancreatic cancer patients results from retention of shed mesothelin in the tumor microenvironment. (Pubmed Central) - May 7, 2022
Measurements of compartment-specific MSLN concentration taken at equilibrium suggested that tumors with poor MSLN secretion efficiency trapped shed MSLN in the tumor microenvironment (TME), a finding confirmed by dynamic experiments using a doxycycline-inducible MSLN expression system...Altogether, these data suggest that PDAC can trap shed MSLN within the TME. This finding has potential significance for design of MSLN-targeted therapeutics.
- |||||||||| doxycycline / Generic mfg., azithromycin / Generic mfg.
Journal: Clinical characteristics and risk factors for severe scrub typhus in pediatric and elderly patients. (Pubmed Central) - May 6, 2022
This study provides evidence that the combination of fosfomycin with either clarithromycin, amoxicillin, doxycycline, or rifampicin (especially with the presence of metronidazole) could be a promising option for treating MDR H. pylori infection. The disease severity rate is comparable between pediatric and elderly ST patients, while different clinical features and laboratory indicators were associated with development of severe complications for pediatric and elderly patients, which is helpful for diagnosis and progress assessment of disease for ST patients.
- |||||||||| doxycycline / Generic mfg.
Journal: Cookiecutter Shark-Related Injuries: A New Threat to Swimming Across the Ka'iwi Channel. (Pubmed Central) - May 6, 2022
Tetanus toxoid was updated, and prophylactic antibiotic coverage, including doxycycline for Vibrio spp., was administered...Immediate life-saving hemorrhage control administered by personnel accompanying the swimmers on the open water is important for preventing morbidity and mortality. Antibiotic prophylaxis for marine bacteria is recommended.
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