In order to explore and develop new anticancer agents, three series of 2-phenylbenzimidazoles,
15-46
, were condensed under simple and mild conditions using sodium metabisulfite as an oxidation agent ...and another series,
47-55
, were obtained
via
a reduction reaction using sodium borohydride. All the compounds synthesized were evaluated for their
in vitro
anticancer activities against three human cancer cell lines. The novel compound
38
was found to be the most potent multi cancer inhibitor against A549, MDA-MB-231, and PC3 cell lines (IC
50
values 4.47, 4.68 and 5.50 μg mL
−1
, respectively). In addition, compound
40
exhibited the best IC
50
value of 3.55 μg mL
−1
against the MDA-MB-231 cell line. The results demonstrated that introducing a new substituent to compounds
37-55
could improve their antiproliferative activities.
Three series of 2-phenylbenzimidazoles obtained under simple and convenient pathways, were used to elucidate their SARs against three cancer cell lines: A549, MDA-MB-231 and PC3.
We sampled nasal-pharyngeal throat swabs from 96,123 asymptomatic individuals at risk of SARS-CoV-2 infection, and generated 22,290 pools at collection, each containing samples from two to seven ...individuals. We detected SARS-CoV-2 in 24 pools, and confirmed the infection in 32 individuals after resampling and testing of 104 samples from positive pools. We completed the testing within 14 days. We would have required 64 days to complete the screening for the same number of individuals if we had based our testing strategy on individual testing. There was no difference in cycle threshold (Ct) values of pooled and individual samples. Thus, compared with individual sample testing, our approach did not compromise PCR sensitivity, but saved 77% of the resources. The present strategy might be applicable in settings, where there are shortages of reagents and the disease prevalence is low, but the demand for testing is high.
Diosmetin (DT) exhibits various biological activities, including anticancer, antibacterial, antioxidant, estrogenic, and, most notably, anti‐inflammatory properties. Although it has a great deal of ...promise for advancement in therapeutic usage, DT has yet to be the subject of many applicable investigations in the realm of pharmacology or medicine in oral or dermal form due to the drawback of being insoluble in water. In this study, the fabrication of carboxymethyl cellulose/polyvinyl alcohol (CMC/PVA) nanofibers loaded with diosmetin (DT) using an electrospinning process was conducted to increase the solubility of DT. After electrospinning, PVA, CMC, and DT are a combination under fixed conditions, providing nano DT fibres having a smooth, homogeneous, non‐granular shape and uniform size of P11C2DT fibre (151 nm) with 82.8 % drug loading efficiency. The nanofibrous membrane P11C2DT was characterized via several physicochemical analyses, including scanning electron microscopy (SEM), Fourier‐transform infrared (FT‐IR), X‐ray diffraction (XRD), thermogravimetric analysis (TGA), and differential scanning calorimetry (DSC). Specifically, the nanofibrous membrane carrier dissolved approximately 85 % of the medication in the release medium after 5 h, starkly contrasting to the powdered form of DT, which did not dissolve in the test environment.
Using electrospinning, PVA, CMC, and diosmetin were employed as matrix polymers to fabricate fiber films (P11C2DT). The FT‐IR, XRD, TGA, and DSC analyses confirmed the presence of DT either in an amorphous state or effectively distributed within P11C2DT. Tt obtained a drug loading efficiency of 82.8 % and a drug dissolution of 85 % within 5 h in a pH 7.4 environment.
Data on breakthrough SARS-CoV-2 Delta variant infections in vaccinated individuals are limited.
We studied breakthrough infections among Oxford-AstraZeneca vaccinated healthcare workers in an ...infectious diseases hospital in Vietnam. We collected demographic and clinical data alongside serial PCR testing, measurement of SARS-CoV-2 antibodies, and viral whole-genome sequencing.
Between 11th–25th June 2021 (7-8 weeks after the second dose), 69 staff tested positive for SARS-CoV-2. 62 participated in the study. Most were asymptomatic or mildly symptomatic and all recovered. Twenty-two complete-genome sequences were obtained; all were Delta variant and were phylogenetically distinct from contemporary viruses obtained from the community or from hospital patients admitted prior to the outbreak. Viral loads inferred from Ct values were 251 times higher than in cases infected with the original strain in March/April 2020. Median time from diagnosis to negative PCR was 21 days (range 8–33). Neutralizing antibodies (expressed as percentage of inhibition) measured after the second vaccine dose, or at diagnosis, were lower in cases than in uninfected, fully vaccinated controls (median (IQR): 69.4 (50.7-89.1) vs. 91.3 (79.6-94.9), p=0.005 and 59.4 (32.5-73.1) vs. 91.1 (77.3-94.2), p=0.043). There was no correlation between vaccine-induced neutralizing antibody levels and peak viral loads or the development of symptoms.
Breakthrough Delta variant infections following Oxford-AstraZeneca vaccination may cause asymptomatic or mild disease, but are associated with high viral loads, prolonged PCR positivity and low levels of vaccine-induced neutralizing antibodies. Epidemiological and sequence data suggested ongoing transmission had occurred between fully vaccinated individuals.
Wellcome and NIH/NIAID
We studied the development and persistence of neutralizing antibodies against SARS-CoV-2 ancestral strain, and Delta and Omicron (BA.1 and BA.2) variants in Vietnamese healthcare workers (HCWs) up to ...15 weeks after booster vaccination. We included 47 HCWs, including group 1 (G1, N = 21) and group 2 (G2; N = 26) without and with breakthrough Delta variant infection before booster immunization, respectively). The study participants had completed primary immunization with ChAdOx1-S and booster vaccination with BNT162b2. Neutralizing antibodies were measured using a surrogate virus neutralization assay. Of the 21 study participants in G1, neutralizing antibodies against ancestral strain, Delta variant, BA.1, and BA.2 were (almost) abolished at month 8 after the second dose, but all had detectable neutralizing antibodies to the study viruses at week 2 post booster dose. Of the 26 study participants in G2, neutralizing antibody levels to BA.1 and BA.2 were significantly higher than those to the corresponding viruses measured at week 2 post breakthrough infection and before the booster dose. At week 15 post booster vaccination, neutralizing antibodies to BA.1 and BA.2 dropped significantly, with more profound changes observed in those without breakthrough Delta variant infection. Booster vaccination enhanced neutralizing activities against ancestral strain and Delta variant compared with those induced by primary vaccination. These responses were maintained at high levels for at least 15 weeks. Our findings emphasize the importance of the first booster dose in producing cross-neutralizing antibodies against Omicron variant. A second booster to maintain long-term vaccine effectiveness against the currently circulating variants merits further research.
The global COVID‐19 pandemic has been associated with high rates of severe acute respiratory syndrome coronavirus 2 (SARS‐CoV‐2) transmission, morbidity and mortality in the general population. ...Evidence‐based guidance on caring for babies born to mothers with COVID‐19 is needed. There is currently insufficient evidence to suggest vertical transmission between mothers and their newborn infants. However, transmission can happen after birth from mothers or other carers. Based on the currently available data, prolonged skin‐to‐skin contact and early and exclusive breastfeeding remain the best strategies to reduce the risks of morbidity and mortality for both the mother with COVID‐19 and her baby.
Vietnam is an important crossroads within Mainland Southeast Asia (MSEA) and a gateway to Island Southeast Asia, and as such exhibits high levels of ethnolinguistic diversity. However, comparatively ...few studies have been undertaken of the genetic diversity of Vietnamese populations. In order to gain comprehensive insights into MSEA mtDNA phylogeography, we sequenced 609 complete mtDNA genomes from individuals belonging to five language families (Austroasiatic, Tai-Kadai, Hmong-Mien, Sino-Tibetan and Austronesian) and analyzed them in comparison with sequences from other MSEA countries and Taiwan. Within Vietnam, we identified 399 haplotypes belonging to 135 haplogroups; among the five language families, the sequences from Austronesian groups differ the most from the other groups. Phylogenetic analysis revealed 111 novel Vietnamese mtDNA lineages. Bayesian estimates of coalescence times and associated 95% HPD for these show a peak of mtDNA diversification around 2.5-3 kya, which coincides with the Dong Son culture, and thus may be associated with the agriculturally-driven expansion of this culture. Networks of major MSEA haplogroups emphasize the overall distinctiveness of sequences from Taiwan, in keeping with previous studies that suggested at most a minor impact of the Austronesian expansion from Taiwan on MSEA. We also see evidence for population expansions across MSEA geographic regions and language families.
Abstract The Diosmetin Phytosome (Dt‐Ph) was developed to enhance the complex's aqueous solubility and in vitro drug release compared to pure Diosmetin (Dt). The process variables such as the ...reactants’ molar ratio, reaction time, stirring speed, and reaction temperature were varied to identify the most appropriate conditions for synthesis. The resulting Dt‐Ph possessed a particle size of 213.9 nm, a zeta potential of −115.1 mV, and a 95.6% encapsulation effectiveness, indicating the successful formation of the phytosome. Scanning electron microscopy (SEM) was used to analyze the morphology of the surface of Dt and Dt‐Ph. The in vitro dissolution in 24 h and normal cell cytotoxic activities of the selected formulation were evaluated. The solubility of Dt‐Ph in buffered media was four times higher than Dt, indicating greater hydrophilicity of Dt‐Ph in comparison to the more lipophilic‐free drug. Additionally, the formulation showed a noticeably increased rate and extent of dissolution studies on drug release, which was two times better than Dt. Cytotoxicity results on HEK‐293A cells showed that Dt‐Ph had less impact on normal cells compared to Dt.
Post-vaccination adverse reactions have been reported with varying symptoms and severity owing to research and production time pressures during the coronavirus disease 2019 (COVID-19) pandemic. In ...this article, we report a rare case of Guillain–Barré syndrome (GBS) in a patient with COVID-19 with acute respiratory distress syndrome (ARDS) after receiving Sinopharm's Vero Cell vaccine (China). The patient who was initially negative for COVID-19 was diagnosed with GBS based on paralysis that developed from the lower extremities to the upper extremities, as confirmed by cytoalbuminologic dissociation in the cerebrospinal fluid. The patient's condition worsened with ARDS caused by COVID-19 infection during the hospital stay, and SpO
2
decreased to 83% while receiving oxygen through a non-rebreather mask (15 l/min) on day 6. The patient was treated with standard therapy for severe COVID-19, invasive mechanical ventilation, and five cycles of therapeutic plasma exchange (TPE) with 5% albumin replacement on day 11 due to severe progression. The patient was weaned off the ventilator on day 28, discharged on day 42, and was completely healthy after 6 months without any neurological sequelae until now. Our report showed the potential of TPE for GBS treatment in critically ill patients with COVID-19 after COVID-19 vaccination.
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•Catalyst-free synthesis of AAIs and BIMs through one-pot multicomponent reaction.•Inhibition study of 25 indole derivatives AAIs and BIMs on MDA-MB-231 cells.•Proposing components ...for anticancer activity in 3-substituted indole structures.•Unraveling their interaction with PARP1 aid in designing more effective compounds.•5h shows favorable drug-like properties for anticancer, as per ADMET analysis.
This study reports a simple process of synthesizing and separating 3-substituted indole derivatives, which are 3-aminoalkylated indoles (AAIs, (C8H7N)CH(CnH2n+1N) and (C8H7N)CH(CnH2n+1NO)) and bis-(3-indolyl) methanes (BIMs, (C8H7N)2CH(CnHn-1O), (C8H7N)2CH(CnHn-2ClO), and (C8H7N)2CH(CnHn+1O3)), via an efficient one-pot multicomponent reaction under catalyst-free conditions. The structures of all obtained compounds were determined via FT-IR, 1D and 2D NMR, and HRMS. Fourteen novel compounds (4f–p and 5e−g) are reported for the first time in this research. The in vitro anticancer activities of all synthesized indoles were investigated on MDA-MB-231 cell line. The results showed that the inhibitory effect of BIMs was better than that of AAIs, and compound 5h with IC50 of 8.73 μM displayed a remarkable anticancer activity on this cell line. In silico docking, the best docking pose 890 of compound 5h docked to topoisomerase I enzyme (1T8I: PDB) to explain the enzyme inhibition mechanism with the values of Free Gibb energy and inhibition constant of −8.95 Kcal·mol−1 and 0.28 µM, respectively. The molecular dynamic (MD) of the best docking pose 890 and 1T8I has performed in Linux environment and the results of simulation indicated the pharmacophore of compound 5h/pose 890 are more hydrophobic and less hydrophilic. In MD simulation, complex of pose 890-1T8I are more stable and residual amino acids are interacted well with pose 890 via two pi-cation interactions such as Lys 587, Tyr 444. The pharmacokinetic model ADMET of compound 5h has been revealed prediction parameters within permissive ranges, the values of log P and log S suggest that 5h exhibits superior solubility in hydrophobic solvents compared to hydrophilic solvents. Compound 5h has the ability to inhibit the majority of CTP enzymes that are involved in phase I oxidative reactions (CYP 1A2, 2C19, 2C9, 2D6, and 3A4). Additionally, the ADMET study suggests that compound 5h has promising drug-like properties for anticancer purposes.
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