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•Tetracycline and its quantum dots for the recognition of Al3+ in milk.•Development of bio-images by applying tetracycline and its dots with cells.•Enhancement of fluorescence for the ...interaction of tetracycline with Al3+ in milk.
We developed a technique that detects Al3+ in milk/bio-samples, and reversibly applied to recognize tetracycline (TC) in milk, enhancing the fluorescence intensity without interference from other cations (Cd2+, Ni2+, Co2+, Sr2+, Mg2+, Fe3+, K+, Sm3+, Ag+, Na+, Ba2+, Cr3+, Zn2+ and Mn2+); the limit of detection (LOD) is found to be 0.00022 mM with r2 = 0.9439. The detection of Al3+ is tested in milk as well as in living cells (Saccharomyces cerevisiae and Debaryomyces spp.) by TC or by its quantum dots. This is consistent with the molecular orbital, revealing that the lowering of the energy of HOMO (Highly Occupied Molecular Orbital) discourages the electron transfer from HOMO of fluorophore to HOMO of excited states of Al-complex that increases the fluorescent intensity. Interestingly, carbon dots (CDs) generated from TC also recognize Al3+ as its LOD is as low as to 0.00050 mM with r2 of 0.9404.
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•The detection of chloride ions by ruthenium complex as chemo-sensor.•Antibacterial properties of ruthenium complex and its behavior over the detection of chloride ions.•Fluorescence ...spectral behavior of the complex over the recognition of chloride ion.•Theoretical studies of ruthenium complex predicting spectral behavior.
A ruthenium complex of 1,5-bis(benzimidazol-2yl)-3-thiapentane (L1) was synthesized, and characterized completely by different analytical techniques. The recognition of chloride by the complex in CH3OH:H2O (3:1, v/v) was studied by the following studies like anion binding tests, interference and titration analyses; the fluorescence results reveal that the ruthenium complex detects selectively chloride ion without any interference from other anions (F−, Br−, I, NO3−, HSO4−, H2PO4−), performing as switch-ON mode, and the stoichiometry ratio of the Ru-complex with chloride was 1:1. This suggests that the interaction of Cl− with the receptor complex would be unfavored Photo Electron Transfer (PET) in the excited state, and it facilitates the electron transfer from HOMO (donor) to low-lying HOMO of the acceptor (fluorophore) increasing the fluorescence intensity. This is consistent with the energy level of the system ruthenium complex with chloride which has been lowered to −9.776 eV from −4.060 eV, preventing the electron transfer effectively, and it enhances the emission intensity. Interestingly, although bacterial cell growth was significantly inhibited in the presence of the complex, it has been further decreased by sensing of chloride ion through the complex.
Randomized controlled trials of the first-line combination of bevacizumab and chemotherapy in patients with metastatic breast cancer (MBC) have shown improvements in tumor response and ...progression-free survival (PFS).
The aim of this ambispective, observational study (LORENA) was to describe the clinical characteristics of long-term responders to bevacizumab-based therapy.
This study consisted of a retrospective and a prospective phase. During the retrospective phase, patients with HER2-negative MBC who were treated with bevacizumab-based first-line therapy were included. During the prospective phase, patients with PFS of ≥12 months were treated according to routine clinical practice procedures. Overall survival (OS) and PFS were estimated using the Kaplan-Meier method. Univariate and multivariate analyses of prognostic factors were performed.
In total, 148 women were included (median age: 50 years; range: 29-81 years). The mean duration of exposure to bevacizumab was 18 months. The majority of patients experienced objective response (complete: 23%; partial: 57%). Median PFS was 22.7 months and median OS was 58.2 months. In multivariate analyses, patients receiving maintenance hormonal therapy (MHT) had longer PFS (
=0.002; hazard ratio HR =1.8) and OS (
=0.009; HR=2.0), while patients not previously treated with taxanes had longer OS (
<0.0001; HR =3.3). No unexpected adverse events were observed.
The results of this study suggest, that among long-term responders, first-line bevacizumab-based therapy is more effective in patients who had not been previously treated with taxanes, and that MHT provides additional therapeutic benefits by extending PFS and OS.
We aimed to evaluate the clinical outcome of Systemic Autoimmune Diseases (SADs) patients hospitalized with COVID-19 in Spain, before the introduction of SARS-CoV-2 vaccines. A nationwide, ...retrospective and observational analysis of the patients admitted during 2020, based on the ICD10 codes in the National Registry of Hospital Discharges, was performed. Among 117,694 patients, only 892 (0.8%) presented any type of SAD before COVID-19-related admission: Sjogren’s Syndrome constituted 25%, Systemic Vasculitides 21%, Systemic Lupus Erythematosus 19%, Sarcoidosis 17%, Systemic Sclerosis 11%, Mixed and Undifferentiated Connective Tissue Disease 4%, Behçet’s Disease 4% and Inflammatory Myopathies 2%. The in-hospital mortality rate was higher in SAD individuals (20% vs. 16%, p < 0.001). After adjustment by baseline conditions, SADs were not associated with a higher mortality risk (OR = 0.93, 95% CI 0.78−1.11). Mortality in the SADs patients was determined by age (OR = 1.05, 95% CI 1.04−1.07), heart failure (OR = 1.67, 95% CI 1.10−2.49), chronic kidney disease (OR = 1.29, 95% CI 1.05−1.59) and liver disease (OR = 1.97, 95% CI 1.13−3.44). In conclusion, the higher COVID-19 mortality rate seen in SADs patients hospitalized in Spain in 2020 was related to the higher burden of comorbidities, secondary to direct organ damage and sequelae of their condition. Whilst further studies should evaluate the impact of baseline immunosuppression on COVID-19 outcomes in this population, efforts should be focused on the optimal management of SAD to minimize the impact of the organ damage that has been shown to determine COVID-19 prognosis.
Cyclin/cyclin‐dependent kinase (CDK) heterodimers have multiple phosphorylation targets and may alter the activity of these targets. Proteins from different metabolic processes are among the ...phosphorylation targets, that is, enzymes of central carbon metabolism. This work explores the interaction of Cyc/CDK complex members with the glycolytic enzymes hexokinase 7 (HXK7) and glyceraldehyde‐3‐phosphate dehydrogenase (GAP). Both enzymes interacted steadily with CycD2;2, CycB2;1 and CDKA;1 but not with CDKB1;1. However, Cyc/CDKB1;1 complexes phosphorylated both enzymes, decreasing their activities. Treatment with a CDK‐specific inhibitor (RO‐3306) or with lambda phosphatase after kinase assay restored total HXK7 activity, but not GAP activity. In enzymatic assays, increasing concentrations of CDKB1;1, but not of CycD2;2, CycB2;1 or CycD2;2/CDKB1;1 complex, decreased GAP activity. Cell cycle regulators may modulate carbon channeling in glycolysis by two different mechanisms: Cyc/CDK‐mediated phosphorylation of targets (e.g., HXK7; canonical mechanism) or by direct and transient interaction of the metabolic enzyme (e.g., GAP) with CDKB1;1 without a Cyc partner (alternative mechanism).
Cell cycle regulators from maize may alter the pace of carbon channeling in glycolysis by two different mechanisms: (a) Cyclin/cyclin‐dependent kinase (CDK) complexes interact with and phosphorylate hexokinase 7; (b) the presence of CDKB, without a cyclin partner, alters the activity of glyceraldehyde‐3‐phosphate dehydrogenase. In both cases, the cell cycle regulators exert an inhibitory effect on the glycolytic enzymes.
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•Ciprofloxacin as chemo-sensor for simultaneous detection of Al3+ and Cu2+.•Logic Gates supported fluorescence for detection of Al3+ in real biological sample.•Ciprofloxacin as ...chemo-sensor for bio-imaging in living cells.
Simultaneous high sensitivity detection of metal ions is important for research in medicine, living cells and environmental samples. In this work, the antibiotic ciprofloxacin (Cipro) is used as a chemosensor for the simultaneous detection of Al3+ and Cu2+ by fluorescent assisted logic gates. The interference of common coexisting metal ions such as Cd2+, Ni2+, Cu2+, Sr2+, Mg2+, Co2+, Fe3+, K+, Al3+, Sm3+, Ag+, Na+, Ba2+, Cr3+, Zn2+, Bi3+ and Mn2+ was tested, and no interference with the simultaneous detection of Al3+ and Cu2+ was found. Interestingly, the fluorescence intensity quenches for Cu2+ and enhances for Al3+ with the increasing concentration of Cipro, showing that it acts as fluorescence-OFF and -ON, respectively; however, with a sequential addition of Cu2+ to Cipro, followed by Al3+, the fluorescence intensity greatly increases, becoming the fluorescence-ON mode. Other combinations of metal ions addition to Cipro do not change the fluorescence behavior. Importantly, the detection of Al3+and Cu2+ in the real samples like living cells was carried out, and it was found that Cipro efficiently performs as fluorescent probe for Al3+ ion in living systems, especially in Saccharomyces cerevisiae; this is confirmed by confocal laser scanning microscopy.
The aim of this study is to investigate whether the primary tumour response to neoadjuvant chemotherapy (NAC), based on the increase in the ADC-values (apparent diffusion coefficient) within the ...breast lesion, could help to predict axillary complete response.
We retrospectively included 74 patients who were treated with NAC followed by surgery at Lucus Augusti Hospital between January 2015 and September 2020. Simple logistic regression was used to evaluate the factors associated with axillary pathological complete response, including the changes in breast tumour ADC-values due to the treatment.
Axillary complete response was correlated with negative oestrogen receptor status, Her2 positivity and response of primary tumour. It was achieved in 31% of the patients. In addition, the increase in the tumour ADC-values with NAC was higher for responders. Among the tumours that demonstrated an increase in ADC-value >0.92 ×10
mm
/s, 42.8% (15/35) showed axillary complete response. Eight (20.5%) breast cancers with an increase in ADC below the cut-off value were found to have no metastatic nodes after treatment (
= 0.038).
Our results suggest that the performance of models predicting axillary response to NAC can be improved by adding the tumour response determined also using diffusion-weighted imaging.
For the fist time, we investigate the relation between tumour response to NAC, assessed using diffusion-weighted imaging, and axillary pathologic complete response.
Despite the high morbidity and mortality of metastatic colorectal cancer (mCRC) in older patients, they have been underrepresented in clinical trials and their optimal treatment is yet to be ...determined. This open-label phase II study evaluated the benefits of panitumumab and capecitabine as a first-line chemotherapy regimen in older patients with wild-type WT RAS mCRC.
Patients (≥70 years; ECOG≤2) received 3-week cycles of panitumumab (9 mg/kg on day 1) plus capecitabine (850 mg/m2 twice daily on days 1–14) until disease progression or unacceptable toxicity. Response was evaluated every 9 weeks according to RECIST_1.1. Outcome measures were: objective response rate (ORR), duration of response (DoR), time to response (TTR), progression (TTP) and treatment failure (TTF), progression-free survival (PFS), overall survival (OS), and safety.
Twenty-seven patients (11 women; median age: 78 years; ECOG: 0 26%, 1 67%, 2 7%) were evaluated. Median follow-up was 17.7 months. Confirmed ORR (95%CI) was 44.4% (25.7–63.2), with 25.9% of patients achieving at least stable disease. Median (95%CI) DoR was 8.7 (5.5–10.4) months, and median TTR was 2.2 (1.9–2.8) months. Median TTP was 9.6 (4.8–11.5) months, with a median TTF of 5.2 (2.8–7.2) months. The median PFS was 7.5 (4.4–10.4) months, and the median OS was 23.7 (7.4–27.5) months. Seventeen (63%) patients reported panitumumab and/or capecitabine-related adverse events grade 3–4, with skin toxicity (18.5%) being the most common. Two (7.4%) deaths were treatment-related.
This study suggests that panitumumab plus capecitabine is a safe and effective regimen in older patients with WT RAS mCRC.
•Panitumumab has a low rate of immunogenicity compared with other antibodies against EGFR because of its fully human nature.•The combination of panitumumab and capecitabine was suggested to be effective in older patients with WT RAS mCRC.•The good tolerability and safety profile of the combination were in line to previous studies in older patients.•Panitumumab with capecitabine may provide an alternative to other anti-EGFR regimens in older patients with WT RAS mCRC.
Organic nanoparticles (ONPs) of lipoic acid and its doped derivatives ONPs/Ag and ONPs/Au were prepared and characterized by UV-Visible, EDS, and TEM analysis. The antibacterial properties of the ...ONPs ONPs/Ag and ONPs/Au were tested against bacterial strains (Staphylococcus aureus, Bacillus cereus, Escherichia coli and Salmonella typhi). Minimal Inhibitory Concentration (MIC) and bacterial growth inhibition tests show that ONPs/Ag are more effective in limiting bacterial growth than other NPs, particularly, for Gram positive than for Gram-negative ones. The order of bacterial cell growth inhibition was ONPs/Ag > ONPs > ONPs/Au. The morphology of the cell membrane for the treated bacteria was analyzed by SEM. The nature of bond formation of LA with Ag or Au was analyzed by molecular orbital and density of state (DOS) using DFT.
Alzheimer’s disease (AD) is one of the most complicated neurodegenerative diseases, and several hypotheses have been associated with its development and progression, such as those involving glucose ...hypometabolism, the cholinergic system, calcium imbalance, inflammation, oxidative imbalance, microtubule instability, and the amyloid cascade, several of which are related to oxidative stress (free radical generation), which contributes to neuronal death. Therefore, several efforts have been made to establish a sporadic AD model that takes into account these hypotheses. One model that replicates the increase in amyloid beta (Aβ) and oxidative stress in vivo is the scopolamine model. In the present work, the chronic administration (6 weeks) of scopolamine was used to analyze the neuroprotective effects of apocynin and galantamine. The results showed that scopolamine induced cognitive impairment, which was evaluated 24 h after the final dose was administered. In addition, after scopolamine administration, the Aβ and superoxide anion levels were increased, and NADPH oxidase 2 (NOX2), nuclear factor erythroid 2-related factor 2 (Nrf2), and nuclear factor kappa B (NFkB) genes were overexpressed. These effects were not observed when either apocynin or galantamine was administered during the last 3 weeks of scopolamine treatment, and although the results from both molecules were related to lower Aβ production and, consequently, lower superoxide anion production, they were likely realized through different pathways. That is, both apocynin and galantamine diminished NADPH oxidase expression, but their effects on transcription factor expression differed. Moreover, experiments in silico showed that galantamine did not interact with the active site of beta secretase, whereas diapocynin, an apocynin metabolite, interacted with the beta-site APP-cleaving enzyme (BACE1) at the catalytic site.
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