Booster BNT162b2 COVID-19 Vaccination Increases Neutralizing Antibody Titers Against the SARS-CoV-2 Omicron Variant in Both Young and Elderly Adults

Concerns about the effectiveness of current vaccines against the rapidly spreading severe acute respiratory syndrome-coronavirus-2 omicron (B.1.1.529) variant are increasing. This study aimed to assess neutralizing antibody activity against the wild-type (BetaCoV/Korea/KCDC03/2020), delta, and omicron variants after full primary and booster vaccinations with BNT162b2. A plaque reduction neutralization test was employed to determine 50% neutralizing dilution (ND₅₀) titers in serum samples. ND₅₀ titers against the omicron variant (median [interquartile range], 5.3 [< 5.0–12.7]) after full primary vaccination were lower than those against the wild-type (144.8 [44.7–294.0]) and delta (24.3 [14.3–81.1]) variants. Furthermore, 19/30 participants (63.3%) displayed lower ND₅₀ titers than the detection threshold (< 10.0) against omicron after full primary vaccination. However, the booster vaccine significantly increased ND₅₀ titers against BetaCoV/Korea/KCDC03/2020, delta, and omicron, although titers against omicron remained lower than those against the other variants (P < 0.001). Our study suggests that booster vaccination with BNT162b2 significantly increases humoral immunity against the omicron variant.     

A single-arm,phase II study of niraparib and bevacizumab maintenance therapy in platinum-sensitive,recurrent ovarian cancer patients previously treated with a PARP inhibitor: Korean Gynecologic Oncology Group (KGOG 3056)/NIRVANA-R trial

BackgroundGiven the expanding clinical use of poly(adenosine diphosphate [ADP]-ribose) polymerase inhibitors (PARPis), there is a significant need for optimal strategies with which to treat patients whose cancer progresses while using a PARPi. However, the treatment consensus after PARPi has not been established. The aim of the Korean Gynecologic Oncology Group (KGOG) 3056/NIRVANA-R trial is to investigate the efficacy of niraparib in combination with bevacizumab as a maintenance therapy in platinum-sensitive ovarian cancer patients who were previously treated with a PARPi.MethodsThe KGOG 3056/NIRVANA-R is a multi-centre, investigator-initiated, single-arm, phase II trial of patients with platinum-sensitive recurrent ovarian cancer recruited from seven KGOG sites. This study included patients with platinum-sensitive recurrent epithelial ovarian cancer who received at least 2 previous courses of platinum-containing therapy and had been treated with a PARPi. Mucinous histology type was excluded. Patients who had responded to the last platinum regimen (either complete or partial response) were eligible to participate in this study. Forty-four patients will be recruited. All enrolled patients are treated with niraparib and bevacizumab for maintenance therapy until disease progression, unacceptable toxicity, or withdrawal of patient consent. The primary endpoint of the study is 6-month progression-free survival rate. Accrual is expected to be completed in 2022, followed by presentation of results in 2023.Trial RegistrationClinicalTrials.gov Identifier: {"type":"clinical-trial","attrs":{"text":"NCT04734665","term_id":"NCT04734665"}}NCT04734665     

Diagnosis of gestational diabetes: Are five rounds of blood sampling necessary?

We aimed to determine the upper and lower cutoff values to simplify the diagnosis of gestational diabetes mellitus (GDM). We investigated the 50-g oral glucose tolerance test (OGTT) results from 1441 pregnancies and identified 423 gravidas who underwent the 100-g OGTT from 2011 to 2019. We collected the results of 50- and 100-g OGTTs. Moreover, we obtained the sum of the 50-g OGTT and 0-hour values, and the sum of those levels and 1-hour values. We determined the upper cutoff at 50-g OGTT, 0-, 1-hour, sum of 50-g OGTT and 0-hour results, and sum of those levels and 1-hour results for the confirmation of GDM. Also, we determined the lower cutoff at these tests for the exclusion of GDM. The upper cutoffs in 50-g OGTT, 0-, 1-hour, the sum of 50-g OGTT and 0-hour were 222, 115, 212, and 315 mg/dL, respectively. The lower cutoffs in 50-g OGTT, 0-, 1-hour, the sum of 50-g OGTT and 0-hour were 131, 65, 151, and 208 mg/dL, respectively. In addition, we discovered that the upper and lower cutoffs in the sum of 50-g OGTT, 0- and 1-hour values were >516 and <373 mg/dL, respectively. We implemented these cutoffs to our study group at 50-g OGTT and 0-, 1-hour of 100-g OGTT. It could omit 2- and 3-hour sampling in 216 gravidas (51.1%). Our approach was able to simplify GDM diagnostic steps in half of our study group.     

Molybdenum Oxide Nanoparticle Aggregates Grown by Chemical Vapor Transport

In this study, the advanced chemical vapor transport (CVT) method in combination with the quenching effect is introduced for creating molybdenum oxide nanoparticle arrays, composed of the hierarchical structure of fine nanoparticles (NPs), which are vertically grown with a homogeneous coverage on the individual carbon fibers of carbon fiber paper (CFP) substrates. The obtained molybdenum oxide NPs hold a metastable high-temperature γ-Mo₄O₁₁ phase along with a stable α-MoO₃ phase by the quenching effect. Furthermore, such a quenching effect forms thinner and smaller nanoparticle aggregates by suppressing the growth and coalescence of primary particles. The molybdenum oxide nanoparticle aggregates are prepared using two different types of precursors: MoO₃ and a 1:1 (mol/mol) mixture of MoO₃ and activated carbon. The results characterized using X-ray diffraction, Raman spectroscopy, X-ray photoelectron spectroscopy, and Fourier-transform infrared spectroscopy show that the relative amount of α-MoO₃ to γ-Mo₄O₁₁ within the prepared NPs is dependent on the precursor type; a lower amount of α-MoO₃ to γ-Mo₄O₁₁ is obtained in the NPs prepared using the mixed precursor of MoO₃ and carbon. This processing–structure landscape study can serve as the groundwork for the development of high-performance nanomaterials in various electronic and catalytic applications.     

The Effect of Methanol on the Structural Parameters of Neuronal Membrane Lipid Bilayers

The structures of the intact synaptosomal plasma membrane vesicles (SPMVs) isolated from bovine cerebral cortexs, and the outer and the inner monolayer separately, were evaluated with 1,6-diphenyl-1,3,5-hexatriene (DPH) and 1,3-di(1-pyrenyl)propane (Py-3-Py) as fluorescent reporters and trinitrophenyl groups as quenching agents. The methanol increased bulk rotational and lateral mobilities of SPMVs lipid bilayers. The methanol increased the rotational and lateral mobilities of the outer monolayers more than of the inner monolayers. n-(9-Anthroyloxy)stearic acid (n-AS) were used to evaluate the effect of the methanol on the rotational mobility at the 16, 12, 9, 6, and 2 position of aliphatic chains present in phospholipids of the SPMVs outer monolayers. The methanol decreased the anisotropy of the 16-(9-anthroyloxy)palmitic acid (16-AP), 12-(9-anthroyloxy)stearic acid (12-AS), 9-(9-anthroyloxy)stearic acid (9-AS), and 6-(9-anthroyloxy)stearic acid (6-AS) in the SPMVs outer monolayer but it increased the anisotropy of 2-(9-anthroyloxy)stearic acid (2-AS) in the monolayers. The magnitude of the increased rotational mobility by the methanol was in the order at the position of 16, 12, 9, and 6 of aliphatic chains in phospholipids of the outer monolayers. Furthermore, the methanol increased annular lipid fluidity and also caused membrane proteins to cluster. The important finding is that was far greater increase by methanol in annular lipid fluidity than increase in lateral and rotational mobilities by the methanol. Methanol alters the stereo or dynamics of the proteins in the lipid bilayers by combining with lipids, especially with the annular lipids. In conclusion, the present data suggest that methanol, in additions to its direct interaction with proteins, concurrently interacts with membrane lipids, fluidizing the membrane, and thus inducing conformational changes of proteins known to be intimately associated with membranes lipids.     

Doxorubicin-Bound Albumin Nanoparticles Containing a TRAIL Protein for Targeted Treatment of Colon Cancer

Purpose

We developed a new nanoparticle formulation comprised of human serum albumin (HSA) for co-delivery of doxorubicin (Dox) and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) with the goal of apoptotic synergy in the treatment of colon cancer.

Methods

TRAIL (0.2, 0.4, 1.0%)- and Dox-loaded HSA nanoparticles (TRAIL/Dox HSA NPs) were prepared by using the nab^TM technology. Morphological and physicochemical characterizations were investigated by dynamic light scattering and transmission electron microscopy. Synergistic cytotoxicity, apoptotic activity, and potential penetration into mass tumor were determined in HCT116 cell-based systems. Furthermore, antitumor efficacy and tumor targeting were also investigated.

Results

TRAIL/Dox HSA NPs were uniformly spherical with sizes of 60?~?120 nm. The encapsulation efficacy of Dox and TRAIL was 68.9–77.2% and 80.4–86.0%, respectively. TRAIL 1.0%/Dox HSA NPs displayed the best inhibition of HCT116 colon cancer cells; inhibition was 6 times higher than achieved with Dox HSA NPs. The TRAIL 1.0%/Dox HSA NPs formulation was studied further. Flow cytometry analysis and TUNEL assay revealed that TRAIL 1.0%/Dox HSA NPs had markedly greater apoptotic activity than Dox HSA NPs. In HCT116 tumor-bearing BALB/c nu/nu mice, TRAIL 1.0%/Dox HSA NPs had significantly higher antitumor efficacy than Dox HSA NPs (tumor volume; 933.4 mm³ vs. 3183.7 mm³, respectively). TRAIL 1.0%/Dox HSA NPs penetrated deeply into tumor masses in a HCT116 spheroid model and localized in tumor sites after tail vein injection.

Conclusions

Data indicate that TRAIL 1.0%/Dox HSA NPs offer advantages of co-delivery of Dox and TRAIL in tumors, with potential synergistic apoptosis-based anticancer therapy.