Sickle cell disease (SCD) is the most common genetic disorder, affecting millions of people worldwide. Aromatic aldehydes, which increase the oxygen affinity of human hemoglobin to prevent ...polymerization of sickle hemoglobin and inhibit red blood cell (RBC) sickling, have been the subject of keen interest for the development of effective treatment against SCD. However, the aldehyde functional group metabolic instability has severly hampered their development, except for voxelotor, which was approved in 2019 for SCD treatment. To improve the metabolic stability of aromatic aldehydes, we designed and synthesized novel molecules by incorporating Michael acceptor reactive centers into the previously clinically studied aromatic aldehyde, 5‐hydroxymethylfurfural (5‐HMF). Eight such derivatives, referred to as MMA compounds were synthesized and studied for their functional and biological activities. Unlike 5‐HMF, which forms Schiff‐base interaction with αVal1 nitrogen of hemoglobin, the MMA compounds covalently interacted with βCys93, as evidenced by reverse‐phase HPLC and disulfide exchange reaction, explaining their RBC sickling inhibitory activities, which at 2 mM and 5 mM, range from 0% to 21% and 9% to 64%, respectively. Additionally, the MMA compounds showed a second mechanism of sickling inhibition (12%–41% and 13%–62% at 2 mM and 5 mM, respectively) by directly destabilizing the sickle hemoglobin polymer. In vitro studies demonstrated sustained pharmacologic activities of the compounds compared to 5‐HMF. These findings hold promise for advancing SCD therapeutics.
Design and synthesis of novel antisickling molecules by incorporating Michael Acceptor reactive centers into the antisickling aromatic aldehyde 5‐HMF. Compounds exhibit dual antisickling mechanism of action by increasing the concentration of the nonpolymer forming sickle hemoglobin, as well as directly destabilizing sickle hemoglobin polymer.
Display omitted
•Blue nitrogen doped carbon nanodots photosensitized wide band gap ZnO nanoparticles photocatalyst.•Improvement of photocatalysis is due to photoluminescence up-conversion properties ...of Carbon nanodots.•Visible-light driven photocatalytic property was enhanced dramatically for carbon dots with ZnO nanoparticles.
Obtaining photochemically stable, efficient, and earth abundant visible-light photocatalyst is still one of the challenging tasks in the photocatalysis area. In the present paper, a new type of nitrogen-doped carbon nanodots, CDs, have been prepared and used as a photosensitizer for a well-known wide-band gap photocatalyst to enhance visible-light driven photocatalytic degradation of an environmental organic pollutant. Blue emitters of nitrogen-doped carbon nanodots (CDs) have been prepared in an aqueous solution via hydrothermal method. ZnO-CDs nanocomposites were prepared via loading of CDs on ZnO in a low temperature mode, in order to modify the optical, electronic, and surface properties of ZnO nanoparticles. The nanocomposites were characterized by UV–vis absorption spectroscopy, X-ray photoelectron spectroscopy, transmission electron microscopy, X-ray diffraction, Raman spectra, and Fourier transform infrared spectroscopy. Photocatalytic degradation of methylene blue (MB) showed that the nanocomposites of ZnO-CDs enhanced the photodegradation efficiency (95% for 100 min) comparing to the pure ZnO in the UV region (365 nm). Interestingly, ZnO-CDs showed enhanced visible light photodegradation comparing with pure ZnO. Such enhancement is attributed to the increase of charge separation rate, photoluminescence up-conversion properties in CDs, and high absorptivity of the ZnO-CDs nanocomposites. Tailoring various CDs with different chemical reactivities and optical properties will eventually lead to harnessing sufficient portion of the solar spectrum in order to obtain high efficient photocatalysts.
Solid state nuclear magnetic resonance (ssNMR) is a powerful and attractive characterization method for obtaining insights into the chemical structure and dynamics of a wide range of materials. ...Current interest in cellulose-based materials, as sustainable and renewable natural polymer products, requires deep investigation and analysis of the chemical structure, molecular packing, end chain motion, functional modification, and solvent-matrix interactions, which strongly dictate the final product properties and tailor their end applications. In comparison to other spectroscopic techniques, on an atomic level, ssNMR is considered more advanced, especially in the structural analysis of cellulose-based materials; however, due to a dearth in the availability of a broad range of pulse sequences, and time consuming experiments, its capabilities are underestimated. This critical review article presents the comprehensive and up-to-date work done using ssNMR, including the most advanced NMR strategies used to overcome and resolve the structural difficulties present in different types of cellulose-based materials.
For the treatment of rhinitis and asthma, a combination of Montelukast sodium and Bilastine has just been approved. Based on the first derivative of synchronous fluorescence, the current work ...developed a green, highly accurate, sensitive, and selective spectroscopic approach for estimating Montelukast sodium and Bilastine in pharmaceutical dosage form without previous separation. The selected technique focuses on measuring the synchronized fluorescence of the studied medications at a fixed wavelength range (Δλ) = 110 nm, and using the amplitude of the first derivative's peak at 381 and 324 nm, for quantitative estimation of Montelukast sodium and Bilastine, respectively. The impacts of different factors on the referred drugs' synchronized fluorescence intensity were investigated and adjusted. The calibration plots for were found to be linear over concentration ranges of 50–2000 ng mL
−1
for Montelukast sodium and 50–1000 ng mL
−1
for Bilastine. Montelukast sodium and Bilastine have LODs of 16.5 and 10.9 ng mL
−1
, respectively. In addition, LOQs were: 49.9 and 33.0 ng mL
−1
, for both drugs, respectively. The developed method was successfully employed to quantify the two drugs in synthetic tablets mixture and in laboratory prepared mixtures containing varied Montelukast and Bilastine ratios. To compare the results with the published analytical approach, a variance ratio F-test and a student t-test were used, which revealed no significant differences.
Angiotensin II (Ang II) is involved in induction and progression of renal damage in diabetes. Angiotensin converting enzyme 2 (ACE2) is highly expressed in the kidney and has been shown to be ...renoprotective by degrading Ang II to Ang-(1-7). A disintegrin and metalloproteinase 17 (ADAM17)-mediated shedding of renal ACE2 contribute to diabetic nephropathy pathogenesis. Lifestyle modification and metformin are recommended as initial therapies for most patients with type 2 diabetes. The aim of this study was to investigate whether exercise training and/or metformin improve glucose homeostasis and albuminuria and downregulate renal ADAM17 and ACE2 shedding in db/db mice. Seven-week-old normal and db/db mice were subjected either to a sedentary existence or exercise training with and without metformin (150 mg/kg per day) for 10 weeks. Exercise training significantly lowered blood glucose, urinary albumin and ACE2 excretion in db/db mice. ADAM17 and ACE2 proteins were co-localized in cortical tubules of the kidney, indicating a possible interaction. Metformin treatment was effective in lowering hyperglycemia only during the first 2 weeks of treatment. Increased renal ADAM17 in 17-week-old db/db mice was corrected by physical exercise but not metformin. In addition, exercise training reduced plasma triglycerides and enhanced insulin levels of db/db mice. In conclusion, exercise training alone and in combination with metformin prevented shedding of renal ACE2 by decreasing ADAM17 protein. Urinary ACE2 could serve as a prognostic tool for the progression of kidney damage and its attenuation by exercise may partially contribute to its renal protection.
In this paper, vilazodone (VLD), a serotonin modulator prescribed for major depressive disorder, was investigated using a rapid, highly sensitive, and eco-friendly spectrofluorometric approach. The ...native fluorescence of VLD, originating from its indole moiety, exhibited an emission peak at 486 nm upon excitation at 241 nm. However, the presence of a piperazinyl nitrogen atom in the VLD structure, acting as an electron donor, significantly diminished the fluorescence intensity through photoinduced electron transfer (PET) to the indole ring. However, by protonating this nitrogen atom using 0.02 M Teorell-Stenhagen buffer (pH 3.5), inhibition of the PET process effectively blocked electron transfer, restoring the fluorescent properties of the drug. Further, an enhancement in the fluorescence was achieved by employing methanol as the solvent, resulting in a 1.5-fold increase. The combined use of PET blockage and methanol enabled the detection of VLD at levels as low as 0.78 ng mL
−1
. Calibration analysis demonstrated linearity within the range 5-400 ng mL
−1
, exhibiting a correlation coefficient of 0.9998 and a limit of quantification of 2.37 ng mL
−1
. The method obeyed the requirements of International Council on Harmonization (ICH). The proposed approach was applied for the accurate measurement of VLD in pharmaceutical tablets, content uniformity testing based on USP requirements, and determining VLD concentration in spiked human plasma. Moreover, the environmental impact, in addition to practical effectiveness, of the proposed approach was evaluated using different metrics.
Blocking photoinduced electron transfer through protonation of the piperazine nitrogen atom using a buffer (pH 3.5).
Intermittent fasting (IF) is a popular dietary plan for weight loss. In fact, fasting is a common practice in different religions such as Buddhism, Hinduism, Judaism, Christianity, and Islam. During ...the month of Ramadan, more than 1.5 billion Muslims worldwide fast from dawn to sunset. Ramadan diurnal intermittent fasting (RDIF) has health benefits, including a reduction in cardiovascular disease (CVD) risk and an improvement in mood. However, little is known about the effects of RDIF on lifestyle behaviors, such as regular exercise, consuming healthy diet, and avoiding harmful substances, as well as mental stress, and academic performance in high school and university students.
In this prospective cohort study, two self-reported questionnaires were sent one week before and during the last week of Ramadan (April 2022; Ramadan 1443 in Hijri Islamic Calendar) to assess changes in lifestyle, perceived stress, and academic achievement of medical students at Taif University in Taif city, Saudi Arabia. Healthy lifestyle components data were collected to calculate healthy lifestyle scores, including body mass index, physical activity, adherence to a Mediterranean diet, smoking status, and sleep duration.
RDIF was associated with a healthier lifestyle in both female and male participants (pre-RDIF mean score: 2.42 vs post-RDIF mean score: 2.74; statistical power = 0.99; P-value < 0.05). They were more active and adherent to the Mediterranean diet during RDIF. Additionally, the post-RDIF smoking rate declined by 53.4%. Male participants showed higher perceived stress scores during RDIF (pre-RDIF mean score: 19.52 vs post-RDIF mean score: 22.05; P-value < 0.01). No changes in academic performance were observed upon RDIF.
Medical students show healthier dietary and lifestyle behaviors and their academic performance is not affected during RDIF. However, perceived stress is higher among male students.
The high-affinity region of a truncated aptamer was applied to the development of a sensitive method for the determination of microcystin-LR (MC-LR) using competitive displacement and molecular ...beacons. In this assay, the fluorophore and quencher labelled complementary sequences of the aptamer are hybridized with the truncated aptamer to form a fluorophore-quencher pair. In the presence of MC-LR, the aptamer duplex dissociates, and the fluorophore-quencher pair is separated. This turn leads to an increase in the yellow fluorescence which is best measured at excitation/emission wavelengths of 555/580 nm. One of the truncated aptamers showed a 50-fold increase in the affinity (0.93 nM) compared to the wild type aptamer (50 nM). The truncated sequence shows considerable cross-reactivity with L congeners but none with other congeners. The assay works in 0.5 to 200 nM MC-LR concentration range. It was applied to spiked tap water samples and gave recoveries around 95 ± 5%.
Graphical abstract
Schematic representation of a method for determination of microcystin-LR via fluorescence that is induced by competitive displacement of complementary DNA strands in a truncated dsDNA aptamer.
Smoking Among Saudi Students Almutairi, Khalid M.
Journal of community health,
10/2014, Letnik:
39, Številka:
5
Journal Article
Recenzirano
This review aims to determine the prevalence of smoking among Saudi students and to study and to identify, synthesize and summarize the predictors that initiate smoking among students in different ...ages in Saudi Arabia. Different databases were searched (Web of Science, Google Scholar, Pub Med and Science Direct) with keywords. This search was carried out in October 2013. Studies that included were evaluated for methodological soundness by giving a quality score based on Russell and Gregory’s criteria. A total 12 relevant articles were included in this review. The findings show that the prevalence of smoking is still in higher rates. The age of smoking was started among adolescents ranged from 10 to 15 years old while from university students were from 16 years old. The main reason for smoking among adolescents was influenced by friends. Among college students were peer pressure followed by the stress, media and imitation of others. Curiosity was a reason for having tried smoking and parents was perceived to be the first source for smoking. Religion was considered the main factor against smoking among the adolescent non-smokers and health consideration among college students. Appropriate smoking control programs on adolescent should be initiated they become the future professionals of the society. Smoking control programs should be considered in this group.
Abstract
Using light to control transient phases in quantum materials is an emerging route to engineer new properties and functionality, with both thermal and non-thermal phases observed out of ...equilibrium. Transient phases are expected to be heterogeneous, either through photo-generated domain growth or by generating topological defects, and this impacts the dynamics of the system. However, this nanoscale heterogeneity has not been directly observed. Here we use time- and spectrally resolved coherent X-ray imaging to track the prototypical light-induced insulator-to-metal phase transition in vanadium dioxide on the nanoscale with femtosecond time resolution. We show that the early-time dynamics are independent of the initial spatial heterogeneity and observe a 200 fs switch to the metallic phase. A heterogeneous response emerges only after hundreds of picoseconds. Through spectroscopic imaging, we reveal that the transient metallic phase is a highly orthorhombically strained rutile metallic phase, an interpretation that is in contrast to those based on spatially averaged probes. Our results demonstrate the critical importance of spatially and spectrally resolved measurements for understanding and interpreting the transient phases of quantum materials.
PDF
