Network-based approach for targeting human kinases commonly associated with amyotrophic lateral sclerosis and cancer

BackgroundAmyotrophic Lateral Sclerosis (ALS) is a rare progressive and chronic motor neuron degenerative disease for which at present no cure is available. In recent years, multiple genes encode kinases and other causative agents for ALS have been identified. Kinases are enzymes that show pleiotropic nature and regulate different signal transduction processes and pathways. The dysregulation of kinase activity results in dramatic changes in processes and causes many other human diseases including cancers.MethodsIn this study, we have adopted a network-based system biology approach to investigate the kinase-based molecular interplay between ALS and other human disorders. A list of 62 ALS-associated-kinases was first identified and then we identified the disease associated with them by scanning multiple disease-gene interaction databases to understand the link between the ALS-associated kinases and other disorders.ResultsAn interaction network with 36 kinases and 381 different disorders associated with them was prepared, which represents the complexity and the comorbidity associated with the kinases. Further, we have identified 5 miRNAs targeting the majority of the kinases in the disease-causing network. The gene ontology and pathways enrichment analysis of those miRNAs were performed to understand their biological and molecular functions along with to identify the important pathways. We also identified 3 drug molecules that can perturb the disease-causing network by drug repurposing.ConclusionThis network-based study presented hereby contributes to a better knowledge of the molecular underpinning of comorbidities associated with the kinases associated with the ALS disease and provides the potential therapeutic targets to disrupt the highly complex disease-causing network

Nanostructured Molybdenum-Oxide Anodes for Lithium-Ion Batteries: An Outstanding Increase in Capacity

This work aimed at synthesizing MoO3 and MoO2 by a facile and cost-effective method using extract of orange peel as a biological chelating and reducing agent for ammonium molybdate. Calcination of the precursor in air at 450 °C yielded the stochiometric MoO3 phase, while calcination in vacuum produced the reduced form MoO2 as evidenced by X-ray powder diffraction, Raman scattering spectroscopy, and X-ray photoelectron spectroscopy results. Scanning and transmission electron microscopy images showed different morphologies and sizes of MoOx particles. MoO3 formed platelet particles that were larger than those observed for MoO2. MoO3 showed stable thermal behavior until approximately 800 °C, whereas MoO2 showed weight gain at approximately 400 °C due to the fact of re-oxidation and oxygen uptake and, hence, conversion to stoichiometric MoO3. Electrochemically, traditional performance was observed for MoO3, which exhibited a high initial capacity with steady and continuous capacity fading upon cycling. On the contrary, MoO2 showed completely different electrochemical behavior with less initial capacity but an outstanding increase in capacity upon cycling, which reached 1600 mAh g−1 after 800 cycles. This outstanding electrochemical performance of MoO2 may be attributed to its higher surface area and better electrical conductivity as observed in surface area and impedance investigations

Impact of opioid-free analgesia on pain severity and patient satisfaction after discharge from surgery: multispecialty, prospective cohort study in 25 countries

Background: Balancing opioid stewardship and the need for adequate analgesia following discharge after surgery is challenging. This study aimed to compare the outcomes for patients discharged with opioid versus opioid-free analgesia after common surgical procedures.Methods: This international, multicentre, prospective cohort study collected data from patients undergoing common acute and elective general surgical, urological, gynaecological, and orthopaedic procedures. The primary outcomes were patient-reported time in severe pain measured on a numerical analogue scale from 0 to 100% and patient-reported satisfaction with pain relief during the first week following discharge. Data were collected by in-hospital chart review and patient telephone interview 1 week after discharge.Results: The study recruited 4273 patients from 144 centres in 25 countries; 1311 patients (30.7%) were prescribed opioid analgesia at discharge. Patients reported being in severe pain for 10 (i.q.r. 1-30)% of the first week after discharge and rated satisfaction with analgesia as 90 (i.q.r. 80-100) of 100. After adjustment for confounders, opioid analgesia on discharge was independently associated with increased pain severity (risk ratio 1.52, 95% c.i. 1.31 to 1.76; P < 0.001) and re-presentation to healthcare providers owing to side-effects of medication (OR 2.38, 95% c.i. 1.36 to 4.17; P = 0.004), but not with satisfaction with analgesia (beta coefficient 0.92, 95% c.i. -1.52 to 3.36; P = 0.468) compared with opioid-free analgesia. Although opioid prescribing varied greatly between high-income and low- and middle-income countries, patient-reported outcomes did not.Conclusion: Opioid analgesia prescription on surgical discharge is associated with a higher risk of re-presentation owing to side-effects of medication and increased patient-reported pain, but not with changes in patient-reported satisfaction. Opioid-free discharge analgesia should be adopted routinely

UPLC–MS-MS Method for the Determination of Vilazodone in Human Plasma: Application to a Pharmacokinetic Study

A sensitive, rapid and simple liquid chromatographic-electrospray ionization tandem mass spectrometric (LC-ESI-MS-MS) method was developed for the quantitative determination of vilazodone in human plasma and for the study of the pharmacokinetic behavior of vilazodone in healthy Egyptian volunteers. With escitalopram as internal standard (IS), liquid-liquid extraction was used for the purification and preconcentration of analytes from human plasma matrix using diethyl ether. The separation was performed on an Acquity UPLC BEH shield RP C18 column (1.7 µm, 2.1 × 150 mm). Isocratic elution was applied using methanol-0.2% formic acid (90:10, v/v). Detection was performed on a triple-quadrupole tandem mass spectrometer with multiple reaction monitoring mode via an electrospray ionization source at m/z 442.21 → 155.23 for vilazodone and m/z 325.14 → 109.2 for escitalopram. Linear calibration curves were obtained over the range of 1-200 ng/mL with the lower limit of quantification at 1 ng/mL. The intra- and inter-day precision showed relative standard deviation ≤3.3%. The total run time was 1.5 min. This method was successfully applied for clinical pharmacokinetic investigation, and a preliminary metabolic study was also carried out

Synthesis of High Surface Area α-K y MnO 2 Nanoneedles Using Extract of Broccoli as Bioactive Reducing Agent and Application in Lithium Battery

International audienceWith the aim to reduce the entire cost of lithium-ion batteries and to diminish the environmental impact, the extract of broccoli is used as a strong benign reducing agent for potassium permanganate to synthesize α-K y MnO 2 cathode material with pure nanostructured phase. Material purity is confirmed by X-ray powder diffraction and thermogravimetric analyses. Images of transmission electron microscopy show samples with a spider-net shape consisting of very fine interconnected nanoneedles. The nanostructure is characterized by crystallite of 4.4 nm in diameter and large surface area of 160.7 m 2 g −1. The material delivers an initial capacity of 211 mAh g −1 with high Coulombic efficiency of 99% and 82% capacity retention after 100 cycles. Thus, α-K y MnO 2 synthesized via a green process exhibits very promising electrochemical performance in terms of initial capacity, cycling stability and rate capability

Table sugar as preparation and carbon coating reagent for facile synthesis and coating of rod-shaped MnO2

Rod-shaped α-MnO2 has been synthesized by a novel and facile wet chemical method using simple sugar and potassium permanganate. Redox reaction between KMnO4 and sucrose is carried out in an acidic medium. Acidic medium provides a reducing character to sucrose through its decomposition to elemental carbon. Carbon coating process was done using simple sugar also as a source for carbon in an absolute ethanol with heating the mixture of α-MnO2 and sugar at 350 °C for an hour in an ambient atmosphere. A single phase of cryptomelane-like phase MnO2 was observed from XRD patterns for bare and carbon coated samples. TGA analysis shows the presence of carbon layer through more weight loss percent of carbon coated sample in comparison with that of carbon free MnO2. Both virgin and carbon coated MnO2 have high thermal stability due to high percent of K inside the tunnel determined from ICP analysis. Transmission Electron Microscope (TEM) showed a rod-shaped crystal for both the parent and carbon coated α-MnO2 and confirmed the presence of a thin film of carbon around MnO2 particles. Both XRD and TEM investigations show that the prepared powders are in nano-scale. Initial capacity of about 140 mAh/g was obtained for the parent and carbon coated samples. The results show also that carbon coating process improves the capacity retention and the efficiency of α-MnO2 in comparison with that carbon free sample

Green Synthesis of Nanoparticles and Their Energy Storage, Environmental, and Biomedical Applications

Green synthesis offers a superior alternative to traditional methods for producing metal and metal oxide nanoparticles. This approach is not only benign and safe but also cost-effective, scalable, and straightforward, operating under ambient conditions. Notable metals and metal oxide nanoparticles, such as manganese oxides, iron oxides, silver, and gold, have been produced using various bio-reductants derived from plant extracts. These biological agents not only expedite the reduction process but also stabilize the nanoparticles, serving dual roles as reducing and capping agents. This review presents the green synthesis of nanoparticles (NPs) obtained from biogenic wastes and plant extracts. The green-synthesized nanostructured MnO2 nanoparticles are evaluated as a potential photocatalyst for water treatment and as an electrode material in lithium-ion batteries and supercapacitors. The green-derived iron oxide nanoparticles are examined as promising antioxidant, anti-inflammatory, and anti-diabetic agents. Additionally, this review discusses the green synthesis of precious metal nanoparticles, specifically silver (Ag NPs) and gold (Au NPs), highlighting their potential medical applications in areas like antiviral treatments and cancer therapy