4 research outputs found
DataSheet_1_Evaluation of dendritic cell-targeting T7 phages as a vehicle to deliver avian influenza virus H5 DNA vaccine in SPF chickens.docx
IntroductionThere is a growing demand for effective technologies for the delivery of antigen to antigen-presenting cells (APCs) and their immune-activation for the success of DNA vaccines. Therefore, dendritic cell (DC)-targeting T7 phages were used as a vehicle to deliver DNA vaccine.MethodsIn this study, a eukaryotic expression plasmid pEGFP-C1-HA2-AS containing the HA2 gene derived from the avian H5N1 virus and an anchor sequence (AS) gene required for the T7 phage packaging process was developed. To verify the feasibility of phage delivery, the plasmid encapsulated in DC-targeting phage capsid through the recognition of AS was evaluated both in vitro and in vivo. The pEGFP-C1-HA2-AS plasmid could evade digestion by DNase I by becoming encapsulated into the phage particles and efficiently expressed the HA2 antigen in DCs with the benefit of DC-targeting phages.ResultsFor chickens immunized with the DC-targeting phage 74 delivered DNA vaccine, the levels of IgY and IgA antibodies, the concentration of IFN-γ and IL-12 cytokines in serum, the proliferation of lymphocytes, and the percentage of CD4+/CD8+ T lymphocytes isolated from peripheral blood were significantly higher than chickens which were immunized with DNA vaccine that was delivered by non-DC-targeting phage or placebo (pConclusionThis study provides a strategy for development of a novel avian influenza DNA vaccine and demonstrates the potential of DC-targeting phage as a DNA vaccine delivery vehicle.</p
Discovery of Metabolite Biomarkers for Acute Ischemic Stroke Progression
Stroke
remains a major public health problem worldwide; it causes
severe disability and is associated with high mortality rates. However,
early diagnosis of stroke is difficult, and no reliable biomarkers
are currently established. In this study, mass-spectrometry-based
metabolomics was utilized to characterize the metabolic features of
the serum of patients with acute ischemic stroke (AIS) to identify
novel sensitive biomarkers for diagnosis and progression. First, global
metabolic profiling was performed on a training set of 80 human serum
samples (40 cases and 40 controls). The metabolic profiling identified
significant alterations in a series of 26 metabolites with related
metabolic pathways involving amino acid, fatty acid, phospholipid,
and choline metabolism. Subsequently, multiple algorithms were run
on a test set consisting of 49 serum samples (26 cases and 23 controls)
to develop different classifiers for verifying and evaluating potential
biomarkers. Finally, a panel of five differential metabolites, including
serine, isoleucine, betaine, PCÂ(5:0/5:0), and LysoPE(18:2), exhibited
potential to differentiate AIS samples from healthy control samples,
with area under the receiver operating characteristic curve values
of 0.988 and 0.971 in the training and test sets, respectively. These
findings provided insights for the development of new diagnostic tests
and therapeutic approaches for AIS
Discovery of CBPD-268 as an Exceptionally Potent and Orally Efficacious CBP/p300 PROTAC Degrader Capable of Achieving Tumor Regression
CBP/p300 proteins are key epigenetic regulators and promising
targets
for the treatment of castration-resistant prostate cancer and other
types of human cancers. Herein, we report the discovery and characterization
of CBPD-268 as an exceptionally potent, effective, and orally efficacious
PROTAC degrader of CBP/p300 proteins. CBPD-268 induces CBP/p300 degradation
in three androgen receptor-positive prostate cancer cell lines, with
DC50 ≤ 0.03 nM and Dmax > 95%, leading to potent cell growth inhibition. It has an excellent
oral bioavailability in mice and rats. Oral administration of CBPD-268
at 0.3–3 mg/kg resulted in profound and persistent CBP/p300
depletion in tumor tissues and achieved strong antitumor activity
in the VCaP and 22Rv1 xenograft tumor models in mice, including tumor
regression in the VCaP tumor model. CBPD-268 was well tolerated in
mice and rats and displayed a therapeutic index of >10. Taking
these
results together, CBPD-268 is a highly promising CBP/p300 degrader
as a potential new cancer therapy
Discovery of CBPD-268 as an Exceptionally Potent and Orally Efficacious CBP/p300 PROTAC Degrader Capable of Achieving Tumor Regression
CBP/p300 proteins are key epigenetic regulators and promising
targets
for the treatment of castration-resistant prostate cancer and other
types of human cancers. Herein, we report the discovery and characterization
of CBPD-268 as an exceptionally potent, effective, and orally efficacious
PROTAC degrader of CBP/p300 proteins. CBPD-268 induces CBP/p300 degradation
in three androgen receptor-positive prostate cancer cell lines, with
DC50 ≤ 0.03 nM and Dmax > 95%, leading to potent cell growth inhibition. It has an excellent
oral bioavailability in mice and rats. Oral administration of CBPD-268
at 0.3–3 mg/kg resulted in profound and persistent CBP/p300
depletion in tumor tissues and achieved strong antitumor activity
in the VCaP and 22Rv1 xenograft tumor models in mice, including tumor
regression in the VCaP tumor model. CBPD-268 was well tolerated in
mice and rats and displayed a therapeutic index of >10. Taking
these
results together, CBPD-268 is a highly promising CBP/p300 degrader
as a potential new cancer therapy