An enzyme free simultaneous detection of γ-amino-butyric acid and testosterone based on copper oxide nanoparticles

Herein, an easy wet-chemical process was used in basic medium with low temperature to prepare low-dimensional copper oxide nanoparticles (CuO NPs). A variety of optical and structural techniques such as UV-visible, FT-IR, XRD, FESEM, XEDS, and XPS were used to characterize the synthesized CuO NPs in detail. Two sensitive and selective sensor probes for γ-amino-butyric acid (GABA) and testosterone (TST) were achieved after modification; a thin layer of NPs on a flat glassy carbon electrode (GCE). Sensor analytical parameters such as sensitivity (SNT), linear dynamic range (LDR), limit of detection (LOD), limit of quantification (LOQ), robustness, and interference effects, were evaluated for the proposed sensor (GCE/CuO NPs) for GABA and TST, based on a dependable current–voltage technique. Calibration curves were found to be linear (R² = 0.9963 and 0.9095) over a broad concentration range of GABA and TST (100.0 pM to 100.0 mM and 10.0 pM to 10.0 mM, respectively). Sensor parameters – SNT (316.46 and 2848.10 pA μM⁻¹ cm⁻²), LDR (100.0 nM to 10.0 mM and 10.0 pM to 1.0 mM), LOD (≈11.70 and 96.67 pM), and LOQ (39.0 and 322.2 pM) – for GABA and TST were calculated from the calibration plot successively. Preparation of CuO NPs using the wet-chemical technique is a good approach for perspective expansion of NPs-based sensors for the enzyme-free detection of biomolecules. Our sensor probe (GCE/CuO NPs) is applied for the cautious recognition of GABA and TST in real biological samples –human, mouse, and rabbit serum – and achieved good and acceptable results.

An easy wet-chemical process was used to prepare copper oxide nanoparticles which were modified and used as sensor probes for γ-amino-butyric acid and testosterone.     

Exploring the gaps in the evidence‐based application of narrowband UVB for the treatment of vitiligo

While narrowband ultraviolet light B (NB‐UVB) has become integral to the treatment of diffuse vitiligo, evidence‐based guidelines have been lacking with regard to dosing and administration. This is largely the result of heterogeneous study designs, ambiguous methodologies, disparate dosing strategies, and the use of varied, and somewhat arbitrary, outcome measures. In the absence of prospective trials to address each of these concerns, the available literature regarding the application of NB‐UVB for vitiligo was reviewed and the authors now pose a set of questions to the phototherapy community in an attempt to highlight gaps within our understanding. We aim to stimulate discussion, elicit expert opinion, and identify areas for future research to move toward a unified and safe treatment guideline for patients afflicted by this disease.     

Upfront DPYD Genotyping and Toxicity Associated with Fluoropyrimidine-Based Concurrent Chemoradiotherapy for Oropharyngeal Carcinomas: A Work in Progress

Simple SummaryThe combination of carboplatin and 5-fluorouracil (5-FU) is effective when used concurrently with radiotherapy for locoregionally advanced oropharyngeal carcinomas. DPYD polymorphisms can be associated with an increased risk of severe toxicity to fluoropyrimidines. Upfront screening for the DPYD*2A allele has been available in the province of Québec, Canada, since March 2017. This study aimed to determine the effect of upfront genotyping on the incidence of grade ≥3 toxicities. We included 181 patients in the analysis. Extended screening for three supplemental at-risk DPYD variants was also retrospectively performed in August 2019. The DPYD*2A, c.2846A>T and c.1236G>A polymorphisms were associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront DPYD genotyping can thus identify patients in whom 5-FU-related toxicity should be avoided.AbstractBackground: 5-FU-based chemoradiotherapy (CRT) could be associated with severe treatment-related toxicities in patients harboring at-risk DPYD polymorphisms. Methods: The studied population included consecutive patients with locoregionally advanced oropharyngeal carcinoma treated with carboplatin and 5-FU-based CRT one year before and after the implementation of upfront DPYD*2A genotyping. We aimed to determine the effect of DPYD genotyping on grade ≥3 toxicities. Results: 181 patients were analyzed (87 patients before and 94 patients following DPYD*2A screening). Of the patients, 91% (n = 86) were prospectively genotyped for the DPYD*2A allele. Of those screened, 2% (n = 2/87) demonstrated a heterozygous DPYD*2A mutation. Extended genotyping of DPYD*2A-negative patients later allowed for the retrospective identification of six additional patients with alternative DPYD variants (two c.2846A>T and four c.1236G>A mutations). Grade ≥3 toxicities occurred in 71% of the patients before DPYD*2A screening versus 62% following upfront genotyping (p = 0.18). When retrospectively analyzing additional non-DPYD*2A variants, the relative risks for mucositis (RR 2.36 [1.39–2.13], p = 0.0063), dysphagia (RR 2.89 [1.20–5.11], p = 0.019), and aspiration pneumonia (RR 13 [2.42–61.5)], p = 0.00065) were all significantly increased. Conclusion: The DPYD*2A, c.2846A>T, and c.1236G>A polymorphisms are associated with an increased risk of grade ≥3 toxicity to 5-FU. Upfront DPYD genotyping can identify patients in whom 5-FU-related toxicity should be avoided.     

Primary amenorrhea secondary to imperforate hymen

Hymen imperforation is uncommon. Symptoms include primary amenorrhea, cyclical lower abdominal pain, and rarely a pelvic mass syndrome. Delayed discovery may lead to endometriosis and infertility. Pelvic ultrasound and nuclear magnetic resonance detect associated genito‐urinary malformations. Hymenectomy is the standard surgical treatment.     

Natural Moroccan clays: Comparative study of their application as recyclable catalysts in Knoevenagel condensation

Natural Moroccan clay samples from different regions were purified via simple washing, activated and extensively analyzed by various characterization techniques. A comparative study of these clays as recyclable heterogeneous catalysts for the Knoevenagel condensation was undertaken in EtOH/water as solvent under mild conditions; high yield of the desired α,β-unsaturated products was obtained in a short reaction period (~ 30 min). The recyclable solid catalyst was effective for several runs indicating that these purified clays are potentially eco-friendly heterogeneous catalysts; assorted α,β-unsaturated carbonyl compounds were synthetized in high yields (~ 98%) at 40 °C.     

Nature is the best source of anti-inflammatory drugs: indexing natural products for their anti-inflammatory bioactivity

Objectives

The aim was to index natural products for less expensive preventive or curative anti-inflammatory therapeutic drugs.

Materials

A set of 441 anti-inflammatory drugs representing the active domain and 2892 natural products representing the inactive domain was used to construct a predictive model for bioactivity-indexing purposes.

Method

The model for indexing the natural products for potential anti-inflammatory activity was constructed using the iterative stochastic elimination algorithm (ISE). ISE is capable of differentiating between active and inactive anti-inflammatory molecules.

Results

By applying the prediction model to a mix set of (active/inactive) substances, we managed to capture 38% of the anti-inflammatory drugs in the top 1% of the screened set of chemicals, yielding enrichment factor of 38. Ten natural products that scored highly as potential anti-inflammatory drug candidates are disclosed. Searching the PubMed revealed that only three molecules (Moupinamide, Capsaicin, and Hypaphorine) out of the ten were tested and reported as anti-inflammatory. The other seven phytochemicals await evaluation for their anti-inflammatory activity in wet lab.

Conclusion

The proposed anti-inflammatory model can be utilized for the virtual screening of large chemical databases and for indexing natural products for potential anti-inflammatory activity.