- |||||||||| Review, Journal: Review of Intra-Articular Use of Antibiotics and Antiseptic Irrigation and Their Systematic Association with Chondrolysis. (Pubmed Central) - Nov 13, 2023
IC50 = 0.31-2.74 mg/mL), neomycin (0.82), cefazolin (1.67-3.95), ceftazidime (3.16-3.59), ampicillin-sulbactam (8.64 - >25), penicillin (11.61), amoxicillin (14.01), imipenem (>25), and tobramycin (>25)...Nine agents should be avoided due to their dose-dependent chondrotoxic effects. Further studies are needed to clarify the safety of these medications for human intra-articular use.
- |||||||||| Jingzhuda (entinostat) / EOC Pharma, EddingPharm
Journal: S100PBP is regulated by mutated KRAS and plays a tumour suppressor role in pancreatic cancer. (Pubmed Central) - Nov 13, 2023
This indicates Kras as an upstream epigenetic regulator of S100PBP. Finally, analysis of TCGA PanCancer Atlas PDAC datasets demonstrated poor prognosis in patients with high S100P and low S100PBP expression, suggesting that S100PBP is a novel tumour suppressor gene with potential clinical utility.
- |||||||||| doxycycline / Generic mfg., azithromycin / Generic mfg.
Journal: Antibiotics that target mitochondria extend lifespan in C. elegans. (Pubmed Central) - Nov 11, 2023
On the other hand, subjecting worms to vitamin C, a pro-oxidant, failed to extend C. elegans lifespan and upregulated its energy consumption, revealing an increase in ATP level. Therefore, our longevity study reveals that mitochondrial inhibitors (i.e., mitochondria-targeting antibiotics) could abrogate aging and extend lifespan in C. elegans.
- |||||||||| Sivextro (tedizolid) / Merck (MSD), Nabriva Therap, Fetroja (cefiderocol) / Shionogi, Xerava (eravacycline) / SOM Biotech, Ewha Womans University, PAION, Innoviva
FDA event, Journal: Computational insights into VacA toxin inhibition: harnessing FDA-approved antibiotics against Helicobacter pylori. (Pubmed Central) - Nov 8, 2023
Furthermore, we also identified the hotspot residue like Asn-506, Tyr-529, and Phe-483 which control the interaction. Concisely, we identified antibiotics that can be repurposed against VacA of H. pylori and explored their molecular mechanism of interaction with VacA.Communicated by Ramaswamy H. Sarma.
- |||||||||| doxycycline / Generic mfg.
Utilising human iPSC-derived neuronal models to investigate novel modulators of TDP-43 pathology (Event Halle, Messe Basel, Ground Floor) - Nov 7, 2023 - Abstract #ALSMND2023ALS_MND_406;
We observed GFP-positive puncta reminiscent of TDP-43 inclusions located within neuronal somas and neurites in a proportion of transduced i3 Neurons after 11 days. Cell Profiler image analysis showed that the majority of puncta were of uniform size and eccentricity.
- |||||||||| doxycycline / Generic mfg.
Phenotyping of the rNLS8 mouse model of amyotrophic lateral sclerosis (Event Halle, Messe Basel, Ground Floor) - Nov 7, 2023 - Abstract #ALSMND2023ALS_MND_216;
At 2 weeks, body weights of the rNLS8 mice started to decline and limb weakness was observable by eye. Ex vivo analyses revealed markedly increased anterior horn total and phosphorylated TDP-43 expression in rNLS8 mice as compared to the tTA control mice.
- |||||||||| apilimod dimesylate (AIT-101) / OrphAI Therap
AIT-101 Improves Functional Deficits in a Human TDP-43 Animal Model of ALS (Event Halle, Messe Basel, Ground Floor) - Nov 7, 2023 - Abstract #ALSMND2023ALS_MND_197;
There were also significant decreases in CSF (p < 0.00001) and plasma (p = 0.03) levels of neurofilament light (NfL). Quantitative IHC staining for hTDP43 and GFAP, a marker of neuroinflammation, showed significant decreases with AIT-101 in several areas of the cortex and corticospinal tract.
- |||||||||| doxycycline / Generic mfg.
Journal: Clinical and laboratory features of rickettsioses in Yucatan, Mexico. (Pubmed Central) - Nov 6, 2023
For the treatment of patients, oral and intravenous doxycycline was used in severe hospitalized cases...Molecular identification allows for greater diagnostic accuracy and timely treatment and consequently a better prognosis. It is necessary to implement or reinforce measures focused on the dissemination of knowledge regarding rickettsial diseases and their prevention.
- |||||||||| gepotidacin (GSK2140944) / GSK, zoliflodacin (ETX0914) / Entasis Therap, Global Antibiotic Research and Development Partnership
Review, Journal: Treatment of bacterial sexually transmitted infections in Europe: gonorrhoea, Mycoplasma genitalium, and syphilis. (Pubmed Central) - Nov 6, 2023
Furthermore, we address the challenges posed by syphilis, where the primary treatment consists of penicillin or doxycycline, with challenges arising in neurosyphilis, allergy, pregnancy, and supply shortages and discuss the ongoing evaluation of alternative antimicrobials (e.g., ceftriaxone, cefixime, linezolid). Our findings identify priority actions and provide concrete solutions for long-term effective management of STIs and antimicrobial resistance mitigation.
- |||||||||| Apretude (cabotegravir extended-release injectable suspension) / ViiV Healthcare, Sunlenca (lenacapavir) / Gilead
Review, Journal: Prevention strategies for sexually transmitted infections, HIV, and viral hepatitis in Europe. (Pubmed Central) - Nov 6, 2023
We examine successful vaccination campaigns against HBV and HPV, the ongoing development of vaccines for chlamydia, syphilis, herpesvirus, and gonorrhoea, and challenges in HIV vaccine research, including lines of research with significant potential like sequential immunization, T-cell responses, and mRNA technology. This review underscores the research endeavors that pave the way for a more resilient and robust approach to combating STIs, HIV, and viral hepatitis in the region.
- |||||||||| KCONVAC (inactivated SARS-CoV-2 Vaccine) / Shenzhen Kangtai
Hand-foot-vulva pustule After COVID-19 inactive vaccine () - Nov 6, 2023 - Abstract #ISDS2023ISDS_177;
The patient was first diagnosed with palmoplantar pustulosis and was prescribed oral acitretin 30mg once daily and topical steroids for one month...Therefore, we chose tripterygium glycosides as an anti-inflammatory and doxycycline to inhibit neutrophil chemotaxis. After being adjusted to a new treatment, the patient recovered.
- |||||||||| doxycycline / Generic mfg.
Journal: Cost of implementing a doxycycline test-and-treat strategy for onchocerciasis elimination among settled and semi-nomadic groups in Cameroon. (Pubmed Central) - Nov 3, 2023
However, it is critical to note that a two-year implementation shows a significantly larger reduction in infection prevalence than the preceding 20 years of annual community-directed treatment with ivermectin. Test-and-treat with doxycycline may be a cost-effective intervention in places where the prevalence of microfilaria is still high, or in hard-to-reach areas where community-directed treatment with ivermectin and MDA coverage are not high enough to stop transmission or where marginalised populations consistently miss treatment.
- |||||||||| Reblozyl (luspatercept-aamt) / BMS, Merck (MSD)
Downregulation of Mitochondrial Complex II (MC II) in Myelodysplastic Syndromes (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_6030;
To understand whether SDH dysregulation alone can contribute to MDS pathobiology, we generated a doxycycline-inducible and reversible mouse model (SDH-KD) that expresses shRNAs against the SDH subunits (SDHA, B, and D) in HSCs. In conclusion, our results indicate that pseudohypoxia- and TGF-
- |||||||||| Jakafi (ruxolitinib) / Novartis, Incyte, CHZ868 - Novartis, Memorial Sloan / Kettering Cancer Center, Mekinist (trametinib) / Novartis, BeiGene
Identifying Targeted Therapies for CBFA2T3-GLIS2 Acute Myeloid Leukemia (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_5603;
Using a doxycycline-inducible knockout (KO) system, we validated JAK2 KO by western blot in three AML cell lines and cells from a patient-derived xenograft (PDX) harboring the fusion...Both the type I JAK2 inhibitor ruxolitinib and the type II JAK2 inhibitor CHZ868 exhibited strong activity in vitro in CBFA2T3 - GLIS2 cell lines and PDX cells, many resistant to cytotoxic chemotherapy...Indeed, treatment with ruxolitinib and the MEK inhibitor trametinib exhibited a synergistic effect when used in combination in cell lines and PDX cells harboring the fusion in vitro, with in vivo testing as a next step...We demonstrated that JAK2 KO or small molecule inhibitors impaired cell viability and induced apoptosis in vitro , and JAK2 KO was highly efficacious in decreasing leukemia burden in vivo . Activation of the MAPK pathway renders resistance to JAK2 inhibitors and the combination of a JAK2 with MEK inhibitor is highly synergistic.
- |||||||||| Mekinist (trametinib) / Novartis, BeiGene, Xospata (gilteritinib) / Astellas
Threshold Attenuation of Perk Signaling Is Sufficient to Overcome RAS-Mediated FLT3 Inhibitor Resistance (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_5600;
We used a doxycycline-inducible system to increase expression of MEKDD, to titrate levels of ERK signaling activation in Molm14 cells...In keeping with this, suppression of pERK levels in Molm14 cells with concurrent RAS mutations to levels below 70% of baseline using the MEK inhibitor (MEKi) trametinib, was sufficient to resensitize to gilteritinib in proliferation assays...Applied clinically, this suggests feasibility of low dose MAPK inhibition in combination with gilteritinib to treat resistant FLT3-activated AML. This strategy that would improve tolerability, a major concern in clinical use of MAPK pathway inhibitors.
- |||||||||| doxycycline / Generic mfg.
Screening for Intracellular Phosphorylation Cascades That Positively and Negatively Regulate the Self-Renewing Proliferation of Immature HPCs (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_5477;
First, Doxycycline-inducible dCas9-VPR (CRISPRa) or dCas9-KRAB-MecP2 (CRISPRi) expression cassettes were introduced into human iPS cells before, and then acted in combination with the phosphorylation-focused sgRNA libraries at the time when HPCs begin to be produced from mesodermal progenitors during their hematopoietic differentiation...On the other hand, the results of CRISPRi showed that suppression of necroptosis-related signalling probably promotes long-term culture of HPCs in the stroma-free, artificial culture circumstances. Our results showed the potential to obtain multipotent HPCs from iPS cells over a long period of time and in large quantities, simply by adjusting the intracellular signals without artificial adding or removing of individual genes.
- |||||||||| doxycycline / Generic mfg.
Fetal MLL-ENL Initiation Induces Developmental Stage-Specific Programs That Restrict Transformation and Depend on MLL3 (Marriott Marquis - Marriott Grand) - Nov 3, 2023 - Abstract #ASH2023ASH_5122;
Fourth, in our prior studies, we developed a doxycycline (DOX) inducible MLL-ENL mouse model (Tet-ME) to activate MLL-ENL and found that transformation efficiency is higher when MLL-ENL is induced shortly after birth rather than before birth (PMID: 31405949)...Quite surprisingly, fetal progenitors appear to be more resistant to transformation than neonatal progenitors, potentially accounting for the paucity of fetal MLLr leukemias. Infant leukemias that do occur must bypass heritable protective mechanisms, either via mutations or epigenetic reprogramming.
- |||||||||| doxycycline / Generic mfg.
Enhancement of Human Neutrophil Bactericidal Activity through ROS Regulation (SDCC - Room 24) - Nov 3, 2023 - Abstract #ASH2023ASH_4784;
Additionally, using the PiggyBac system, we established doxycycline-inducible NRROS expression clones (homo-KO+Dox) based on homo-KO clones...In conclusion, NRROS knockout in human neutrophils enhances bactericidal capacity through heightened ROS production, offering promising prospects for innovative infectious disease treatments. If successfully harnessed, this innovative treatment modality could revolutionize infectious disease management, combating drug-resistant infections, and improving global health outcomes.
- |||||||||| doxycycline / Generic mfg.
T-Cell Signaling Mediates the Epigenetic Priming of Germinal Center B-Cell Plasticity and Stem Functionality (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_3713;
Therefore, we investigated the potential of GC B cells to form iPSCs using a doxycycline-dependent mouse strain that enables the inducible expression of Yamanaka transcription factors (TF) in any given cell...We speculate that restricting plasticity to B cells under selection by T cells, limits the potential for GC B cells to acquire high levels of plasticity, hence reducing the potential for these cells to initiate lymphomas. Consistent with this notion, we found that DLBCL patients enriched for these stem cell signatures manifested inferior clinical outcomes.
- |||||||||| doxycycline / Generic mfg.
The Oncoprotein SKI As a Driver in KMT2A-MLLT3/NRasG12D-Positive Acute Myeloid Leukemia (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_3696;
Upon disease onset, shRNA expression was induced by doxycycline treatment...In contrast to Myb KD in the RN2 cells, Ski KD led to a lower expression of canonical KMT2A target genes, implicating that Ski may be part of KMT2A complexes in AML. In summary, SKI seems to be crucial for KMT2A-MLLT3/NRasG12D-driven AML and may be a potential target for new therapeutic strategies.
- |||||||||| doxycycline / Generic mfg.
Roles for Heme Synthesis in the Maintenance of Hematopoietic Stem and Progenitor Cells (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_3622;
We also revealed that CPOX inhibition under doxycycline inducible CRISPR Cas9 system caused cell growth inhibitory effect and cell death in these cells...Dysfunctions of heme synthesis in HSPCs can cause their aberrance by the alterations in their mitochondrial status which can cause apoptosis and/or differentiation arrest. Considering the metabolic differences (i.e., demands for mitochondrial oxidative phosphorylation and subsequent ATP synthesis) between normal HSPCs and leukemia or unperturbed hematopoiesis and perturbed hematopoiesis (i.e., infections and hematopoietic stem cell transplantations), further analysis to reveal the roles for heme synthesis in the maintenance of HSPCs will pave the way to establish optical approaches in these clinical settings.
- |||||||||| Branigen (acetyl-L-carnitine) - Mitsubishi Tanabe, Dong / A, Leadiant Biosci
Decline in Cardiolipin in Hematopoietic Stem Cell during Aging Alters Their Regenerative Potential (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_3614;
This study indicates that HSC mitochondrial membrane lipids become abnormal with aging which causes a decline in HSC function and highlights the critical role of mitochondrial cardiolipin in HSC functions. It implies that metabolite supplementation is a viable option for restoring age-related HSC functional defects.
- |||||||||| tamoxifen / Generic mfg., doxycycline / Generic mfg.
Rapid Degradation of mDia2 Protein during Terminal Erythropoiesis Via an In Vivo Aid System: An Alternative Approach for Loss-of-Function Studies (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_3369;
Tamoxifen-induced conditional gene expression, gene knockdown, or cell tracking represent some of the most common genetic manipulations employed in mice...Similar observations have been made with the in vivo doxycycline-inducible system...This suggests that rapid mDia2 loss, induced by the AID system, permits a better understanding of the targeted protein's function by avoiding potential compensatory effects from mDia1 during terminal enucleation. In conclusion, our established in vivo AID system enables rapid targeted protein degradation and serves as a powerful tool for studying protein functions potentially obscured by compensatory effects during erythropoiesis.
- |||||||||| doxycycline / Generic mfg.
Functional Dissection of Cellular Programs to Uncover Novel Gene Dependencies in AML (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_1798;
In conclusion, our established in vivo AID system enables rapid targeted protein degradation and serves as a powerful tool for studying protein functions potentially obscured by compensatory effects during erythropoiesis. Doxycycline-inducible shRNA directed against CDK13 also impaired AML progression in the peripheral blood and bone marrow in an MV4-11- KMT2A r xenograft...Mechanistically, our data support that CDK13 controls Pol2 processivity, with CDK13 perturbation leading to a decreased occupancy at the 3
- |||||||||| doxycycline / Generic mfg., cytarabine / Generic mfg.
Uncovering the Role of CD59 As a Novel Therapeutic Target Against High-Risk Acute Myeloid Leukemia (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_1781;
To study the role of CD59 in AML, we constructed doxycycline-inducible short-hairpin RNA (shRNA) expression vectors against CD59 (shCD59) and a non-targeting control (shNT) and transduced them into SKM-1, HL-60, EOL-1, and OCI-M1 AML cell lines...The survival outlook for high-risk AML patients has remained unchanged for the past 25 years. Our findings offer valuable insights that can significantly alter the current treatment landscape of AML.
- |||||||||| doxycycline / Generic mfg.
Hematopoietic Stem and Progenitor Cells Acquire an Inflammatory Memory of the Acute Myeloid Leukemia Niche (SDCC - Halls G-H) - Nov 3, 2023 - Abstract #ASH2023ASH_1731;
To further ascertain disease relevance and reproducibility we turned to a doxycycline-inducible (i)MLL-AF9 AML model...Our experiments phenocopy observations of trained immunity in other experimental systems, and suggest the acquisition of an innate immune memory in the AML niche. Immune priming may impact the role of these HSPC in the context of inflammation associated with aging, or clones with predisposing molecular lesions such as TET2 or DNMT3A.
- |||||||||| doxycycline / Generic mfg.
Macropinocytosis As a Means of Selectively Targeting RAS-Mutant Multiple Myeloma (Grand Hyatt - Grand Hall D) - Nov 3, 2023 - Abstract #ASH2023ASH_954;
MDC-MMAE was pre-clinically evaluated both in-vitro and in-vivo , in human MM cell lines, patient cells and a doxycycline inducible mutant KRAS cell system...It can also be combined with other MM standard of care drugs and with immunotherapy drugs to have a potentially important clinical effect. In collaboration with Tezcat Biosciences, the MDC-MMAE technology has achieved a phase II SBIR for advancement to clinical application.
|
