ABSTRACT
Patients undergoing hemodialysis (HD) are particularly vulnerable to coronavirus disease 2019 (COVID-19) and are at increased risk of developing severe infection. However, given the exclusion of such patients from clinical trials, there are limited data regarding the effectiveness of the antiviral drug nirmatrelvir/ritonavir (N/R) in patients on HD. We prescribed N/R to 4 patients on HD with COVID-19 after obtaining informed consent. Their clinical symptoms were improved at approximately 3 days after N/R administration. The viral load was reduced after approximately 10 days. The main adverse effects were nausea and vomiting. Rational dosage adjustment obtained good tolerance but did not influence the efficacy. These results suggest that N/R may be a promising agent for patients on HD with COVID-19.
Subject(s)
COVID-19 , Humans , COVID-19 Drug Treatment , Ritonavir/therapeutic use , Renal Dialysis/adverse effects , Antiviral Agents/adverse effectsABSTRACT
In this study, a series of curcumin derivatives containing 1,2,3-triazole were designed and synthesized, and their inhibitory activities against the proliferation of lung cancer cells were studied. Compound 5 k (3,4-dichlorobenzyltriazole methyl curcumin) had the best activity against A549 cells, with a half-maximal inhibitory concentration (IC50 ) of 2.27â µM, which was approximately 10 times higher than that of the lead curcumin and higher than that of gefitinib (IC50 =8.64â µM). Western blotting revealed that 5 k increased the phosphorylation levels of p38, c-Jun N-terminal kinase (JNK), and extracellular signal-regulated kinase (ERK). Compound 5 k also promoted the expression of the inhibitor of nuclear factor-κB (IκBα) and decreased that of nuclear factor-κB (NF-κB), signal transducer and activator of transcription 3 (STAT3), and ß-catenin. Therefore, 5 k suppresses A549 cell proliferation by activating the mitogen-activated protein kinases and suppressing NF-κB/STAT3 signaling pathways. So, 5 k can potentially be used for treating non-small cell lung cancer.
Subject(s)
Antineoplastic Agents/pharmacology , Antioxidants/pharmacology , Curcumin/pharmacology , Lung Neoplasms/drug therapy , Triazoles/pharmacology , Animals , Antineoplastic Agents/chemical synthesis , Antineoplastic Agents/chemistry , Antioxidants/chemical synthesis , Antioxidants/chemistry , Biphenyl Compounds/antagonists & inhibitors , Cell Proliferation/drug effects , Cell Survival/drug effects , Cells, Cultured , Curcumin/chemical synthesis , Curcumin/chemistry , Dose-Response Relationship, Drug , Drug Screening Assays, Antitumor , Humans , Lung Neoplasms/metabolism , Lung Neoplasms/pathology , Mitogen-Activated Protein Kinases/antagonists & inhibitors , Mitogen-Activated Protein Kinases/metabolism , Molecular Structure , NF-kappa B/antagonists & inhibitors , NF-kappa B/metabolism , Neoplasms, Experimental/drug therapy , Neoplasms, Experimental/metabolism , Neoplasms, Experimental/pathology , Picrates/antagonists & inhibitors , STAT3 Transcription Factor/antagonists & inhibitors , STAT3 Transcription Factor/metabolism , Structure-Activity Relationship , Triazoles/chemical synthesis , Triazoles/chemistry , ZebrafishABSTRACT
We investigated the reactions between cobalt-oxides and water molecules using photoelectron spectroscopy and density functional calculations. It has been confirmed by both experimental observation and theoretical calculations that dihydroxide anions, Co(m)(OH)(2)(-) (m = 1-3), were formed when Co(m)O(-) clusters interact with the first water molecule. Addition of more water molecules produced solvated dihydroxide anions, Co(m)(OH)(2)(H(2)O)(n)(-) (m = 1-3). Hydrated dihydroxide anions, Co(m)(OH)(2)(H(2)O)(n)(-), are more stable than their corresponding hydrated metal-oxide anions, Co(m)O(H(2)O)(n+1)(-).
ABSTRACT
Manganese polysulfide cations, MnS(x)(+) (x = 1-10), were studied with mass-selected photodissociation experiments and density functional calculations. We found that MnS(+), MnS(2)(+) and MnS(3)(+) undergo dissociation at 355 nm by loss of S, S(2) and S(3), respectively. The dissociation of larger clusters is relatively complex because of the existence of multiple isomers and multiple dissociation channels. The geometric structures of the low-lying isomers found by theoretical calculations are consistent with the dissociation channels observed in the experiments. The dissociation of MnS(x)(+) clusters occurs mainly by breaking of the Mn-S bonds since they are weaker than the S-S bonds.
