Molecular docking, ADMET and molecular dynamics simulation revealed metralindole as a multitargeted inhibitor for division kinases

Abstract Lung cancer is the most common type of cancer in the world, and alone, in 2020, almost 2.21 million new cases were diagnosed, with 1.80 million deaths, and are increasing daily. Non-small cell lung (NSCLC) is the primary type of lung cancer, predominantly forms around 80% of cases compared to small cell carcinoma, and about 75% of patients are already in an advanced state when diagnosed. Despite notable advances in early diagnosis and treatment, the five-year survival rate for NSCLC is not encouraging. Therefore, it is crucial to investigate the molecular causes of non-small cell lung cancer to create more efficient therapeutic approaches. Lung cancer showed a more significant and persistent binding affinity and energy landscape with the target CDK2 staurosporine and FGF receptor-1. In this study, we have picked two essential target proteins, human cyclin-dependent kinase-2 and Human Protein Kinase CK2 Holoenzyme and screened the entire prepared DrugBank prepared library of 1,55,888 compounds and identified 2-(2-methyl-5-nitroimidazole-1-yl) ethanol (Metralindole) as a major inhibitor. Metralindole has displayed high docking scores of -5.159 Kcal/mol and -5.99 Kcal/mol with good hydrogen bonding and other bonding topologies such as van der Waals force, and ADMET results shown excellent bioavailability, outstanding solubility, no side effects, and toxicity. The molecular dynamics simulation for 100ns in a water medium confirmed the compound's stability and interaction pattern with the lowest deviation and fluctuations. Our in-silico study suggests Metralindole, an experimental compound, can effectively cure lung cancer. Further, the experimental validation of the compound is a must before any prescription

Organization Readiness and ERP Implementation in Albaha University

This work studies the correlation between the organizational readiness in Albaha University and the respective Critical Success Factors with regards to the Enterprise Resource Planning (ERP) implementation. The study also considers some suggestions to improve the ABU’s ERP systems and roadmap towards the self –development strategy and to reduce vendor-dependency. A survey regarding ERP to the end-users, experts and developers in Albaha University was conducted. The analysis of the results in this work confirmed with the results of an existing work. The four significance success factors: Project Management, Business Process Re-engineering, System Integration, and Training and Education are recommended to be adopted to assure the smooth adoption of ERP at Albaha University

Lessons learned from COVID-19 Lockdown: An ASPED/MENA Study on Lifestyle Changes and Quality of Life during Ramadan Fasting in Children and Adolescents living with Type 1 Diabetes

Background: Lockdown was a unique experience that affected many aspects of life, particularly during the challenge of Ramadan fasting (RF). Studying this can increase understanding of the effects of lifestyle changes on quality of life (QoL) for children with type 1 diabetes (T1D) during RF. Methods: A cross-sectional study that assessed the effect of lockdown on lifestyle and QoL on fasting children living with T1D during Ramadan in the Middle East and North Africa region (2020-2021). We compared the child (self) and parent (proxy) reports using PEDQoL v3.0 disease specific questionnaire during lockdown and non-lockdown periods, and assessed correlations with lifestyle changes using regression and gap analyses. Results: A total of 998 reports from 499 children with T1D aged 8-18 years (study=276, control=223), and their parents during RF in lockdown and non-lockdown periods. Fathers were more involved in their children’s care during lockdown (p=0.019). Patients had better compliance with treatment (p= 0.002), a reversed sleep pattern (p= 0.033), increased food intake (p=<0.001) and less exercise (p<0.001). Children and parents perceived better QoL during lockdown (p=<0.001) with no differences between their reports in “Diabetes Symptoms”, “Treatment Adherence” and “Communication” domains. Self and proxy reports were different in all domains during non-lockdown (p-values <0.001- 0.009). In gap analysis, although not statistically significant, the gap was approximated between children’s and parents’ perceptions in all domains during lockdown. Conclusion: COVID-19 lockdown had a positive impact on QoL of children living with T1D during RF, possibly due to lifestyle changes and superior psychosocial family dynamics

Decay spectroscopy at the two-proton drip line: radioactivity of the new nuclides 160Os and 156W

The radioactivity of 76160Os84 and 74156W82 that lie at the two-proton drip line have been measured in an experiment performed at the Accelerator Laboratory of the University of Jyväskylä. The 160Os nuclei were produced using fusion-evaporation reactions induced by a beam of 310 MeV 58Ni ions bombarding a 106Cd target. The 160Os ions were separated in flight using the recoil separator MARA and implanted into a double-sided silicon strip detector, which was used to measure their decays. The α decays of the ground state of 160Os (Eα = 7092(15) keV, t1/2 = 97−32+97 μs) and its isomeric state (Eα = 8890(10) keV, t1/2 = 41−9+15 μs) were measured, allowing the excitation energy of the isomer to be determined as 1844(18) keV. These α-decay properties and the excitation energy of the isomer are compared with systematics. The α decays were correlated with subsequent decays to investigate the β decays of the ground state of 156W, revealing that unlike its isotones, both low-lying isomers were populated in its daughter nuclide, 156Ta. An improved value for the half-life of the proton-decaying high-spin isomeric state in 73156Ta83 of 333−22+25 ms was obtained in a separate experiment using the same experimental systems with a 102Pd target. This result was employed to improve the precision of the half-life determined for 156W, which was measured as 157−34+57 ms

Current Data on and Clinical Insights into the Treatment of First Episode Nonaffective Psychosis: A Comprehensive Review

Implementing the most suitable treatment strategies and making appropriate clinical decisions about individuals with a first episode of psychosis (FEP) is a complex and crucial task, with relevant impact in illness outcome. Treatment approaches in the early stages should go beyond choosing the right antipsychotic drug and should also address tractable factors influencing the risk of relapse. Effectiveness and likely metabolic and endocrine disturbances differ among second-generation antipsychotics (SGAs) and should guide the choice of the first-line treatment. Clinicians should be aware of the high risk of cardiovascular morbidity and mortality in schizophrenia patients, and therefore monitoring weight and metabolic changes across time is mandatory. Behavioral and counseling interventions might be partly effective in reducing weight gain and metabolic disturbances. Ziprasidone and aripiprazole have been described to be least commonly associated with weight gain or metabolic changes. In addition, some of the SGAs (risperidone, amisulpride, and paliperidone) have been associated with a significant increase of plasma prolactin levels. Overall, in cases of FEP, there should be a clear recommendation of using lower doses of the antipsychotic medication. If no or minimal clinical improvement is found after 2 weeks of treatment, such patients may benefit from a change or augmentation of treatment. Clinicians should provide accurate information to patients and relatives about the high risk of relapse if antipsychotics are discontinued, even if patients have been symptom free and functionally recovered on antipsychotic treatment for a lengthy period of time.This review was carried out at the Hospital Marque´s de Valdecilla, University of Cantabria, Santander, Spain, with the following Grant support: Instituto de Salud Carlos III PI020499, PI050427, PI060507, Plan Nacional de Drugs Research Grant 2005-Orden sco/3246/2004, SENY Fundacio´ Research Grant CI 2005-0308007, Fundacio´n Marque´s de Valdecilla API07/011 and CIBERSAM

Naringenin ameliorates Cyclophosphamide-induced nephrotoxicity in experimental model

Cyclophosphamide (CP) is widely described in the management of several nonneoplastic and neoplastic disorders. Renal damage is the most reported toxic effect of CP in clinical practice.Our study aimed to evaluate the effect of Naringenin (NG) in attenuating renal damage induced by CP in an experimental model.A total of 32 rats were divided into four groups (n = 8): negative control: rats fed on a basal diet, positive control: rats injected intraperitoneally with CP 50 mg/kg of body weight/day, NG 100: rats treated with NG 100 mg/kg/day body orally with concomitant administration of CP as described before, and NG 200: rats treated with NG 200 mg/kg/day body orally daily + CP. At the end of the experimental protocol (21 days), blood creatinine and urea levels were measured. The antioxidant activities and lipid peroxidation products were measured in the renal tissues as indicators of oxidative damage. Histopathological examination and immunohistochemistry staining were also performed on renal tissues.Coadministration of NG along with CP significantly (p < 0.001) improved the renal function and antioxidant capacities compared with positive control animals. Furthermore, histopathological, and immunological examination of renal tissue confirmed the protective effect of NG against CP-induced nephrotoxicity.The current study showed that NG has the potential to protect CP-induced renal damage, which may be beneficial for further studies and the design of NG analogs to be useful in clinical practice against CP-induced nephrotoxicity

Quercetin Nanoemulsion Ameliorates Neuronal Dysfunction in Experimental Alzheimer&rsquo;s Disease Model

Aluminum is the most abundant metal that can get admission to the human through several means that include our food, drinking water, cans, drugs, and deodorants, causing neurodegenerative diseases such as Alzheimer&rsquo;s disease (AD). The present study aims to evaluate the role of quercetin nanoemulsion (QCNE) in attenuating neuronal dysfunction in aluminum chloride (AlCl3)-induced experimental AD. All animals were classified into six groups including negative control group (I): received a vehicle; QC group: received intraperitoneal (IP) injection of QC; Alzheimer&rsquo;s group: received AlCl3 orally; treated group (I): received AlCl3 orally and IP injection of QC; treated group (II): received AlCl3 orally and QC orally; and treated group (III): received AlCl3 orally and IP injection of QCNE. At the end of the experimental period (30 days), the brain was used to study biochemical parameters (measurement of neurotransmitters (serotonin, dopamine, and norepinephrine), oxidant/antioxidant parameters (reduced glutathione, malondialdehyde, superoxide dismutase, and advanced oxidation protein product), and inflammatory markers (adiponectin, interleukin 1&beta;, and plasma tumor necrosis factor-alpha)), while another part was for brain immune-histochemical analysis (study cyclooxygenases (COX-1 and COX-2)). Results showed that the mean value of oxidative stress markers was significantly increased in the AD group as well as the inflammatory biomarkers and all the study neurotransmitters, whereas these parameters were attenuated in treated groups, especially those that received QCNE. The immunohistochemistry findings confirm our results. Both approaches (QC and QCNE) succeeded in retracting the negative impact of AlCl3. Meanwhile, the effect of QCNE is more potent in mitigating the impact mediated by AlCl3 in treated animals. In conclusion, the treatment mainly by QCNE has huge potential in protecting against AlCl3-induced neuronal dysfunction, as shown in our results by the elevation of brain antioxidant/anti-inflammatory activities and neurotransmitter levels as well as mending of the histopathological changes in animal models