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Background: Bladder cancer (BCa), the sixth commonest cancer in the USA, is highly lethal when metastatic. Spatial and temporal patterns of patient-specific metastatic spread are deemed random and unpredictable. Whether BCa metastatic patterns can be quantified and predicted more accurately is unknown. Objective: To develop a web-based calculator for forecasting metastatic progression in individual BCa patients. Design, setting, and participants: We used a prospectively collected longitudinal dataset of 3503 BCa patients who underwent a radical cystectomy following diagnosis and were enrolled continuously. We subdivided patients by their pathologic subgroup stages of organ confined (OC), extravesical (EV), and node positive (N+). We illustrated metastatic pathway progression using color-coded, circular, tree ring diagrams. We created a dynamical, data-visualization, web-based platform that displays temporal, spatial, and Markov modeling figures with predictive capability. Outcome measurements and statistical analysis: Patients underwent history and physical examination, serum studies, and liver function tests. Surveillance follow-up included computed tomography scans, chest x-rays, and radiographic evaluation of the reservoir and upper tracts, with bone scans performed only if clinically indicated. Outcomes were measured by time to clinical recurrence and overall or progression-free survival. Results and limitations: Metastases developed in 29% of patients (n = 812; median follow-up 15.3 yr), with 5-yr overall survival of 20.2%, compared with 78.6% in those without metastases (n = 1983; median follow-up 10.9 yr). The three commonest sites of spread at the time of first progression were bone (n = 214; 26.4%), pelvis (n = 194; 23.9%), and lung (n = 194; 23.9%). The order and frequency of these sites vary when divided by pathologic subgroup stages of OC (lung [n = 65; 25.1%], urethra [n = 45; 17.4%], and bone [n = 29; 11.2%]), EV (pelvis [n = 63; 33.0%], bone [n = 45; 23.6%], and lung [n = 29; 15.2%]), and N+ (bone [n = 111; 30.7%], retroperitoneum [n = 70; 19.3%], and pelvis [n = 60; 16.6%]). Markov chain modeling indicated a higher probability of spread from bladder to bone (15.5%), pelvis (14.7%), and lung (14.2%). Conclusions: Our web-based calculator allows real-time analyses in the clinic based on individual patient-specific demographic and cancer data elements. For contrasting subgroups, the models indicated differences in Markov transition probabilities. Spatiotemporal patterns of BCa metastasis and sites of spread indicated underlying organotropic mechanisms in the prediction of response. This recognition opens the possibility of organ site–specific therapeutic targeting in the oligometastatic BCa setting. In the precision medicine era, visualization of complex, time-resolved clinical data will enhance management of postoperative metastatic BCa patients. Patient summary: We developed a web-based calculator to forecast metastatic progression for individual bladder cancer (BCa) patients, based on the clinical and demographic information obtained at diagnosis. This can help in predicting disease status and survival, and improving management in postoperative metastatic BCa patients. Take Home Message: Future pathways of metastatic progression for individual bladder cancer patients can be determined based on currently available clinical and demographic information obtained at diagnosis. In focused subgroups of patients, these metastatic spread patterns can also portend disease status and survival.

This study delves into the therapeutic efficacy of A. pyrethrum in addressing vitiligo, a chronic inflammatory disorder known for inducing psychological distress and elevating susceptibility to autoimmune diseases. Notably, JAK inhibitors have emerged as promising candidates for treating immune dermatoses, including vitiligo. Our investigation primarily focuses on the anti-vitiligo potential of A. pyrethrum root extract, specifically targeting N-alkyl-amides, utilizing computational methodologies. Density Functional Theory (DFT) is deployed to meticulously scrutinize molecular properties, while comprehensive evaluations of ADME-Tox properties for each molecule contribute to a nuanced understanding of their therapeutic viability, showcasing remarkable drug-like characteristics. Molecular docking analysis probes ligand interactions with pivotal site JAK1, with all compounds demonstrating significant interactions; notably, molecule 6 exhibits the most interactions with crucial inhibition residues. Molecular dynamics simulations over 500ns further validate the importance and sustainability of these interactions observed in molecular docking, favoring energetically both molecules 6 and 1; however, in terms of stability, the complex with molecule 6 outperforms others. DFT analyses elucidate the distribution of electron-rich oxygen atoms and electron-poor regions within heteroatoms-linked hydrogens. Remarkably, N-alkyl-amides extracted from A. pyrethrum roots exhibit similar compositions, yielding comparable DFT and Electrostatic Potential (ESP) results with subtle distinctions. These findings underscore the considerable potential of A. pyrethrum root extracts as a natural remedy for vitiligo., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024. Published by Elsevier Ltd.)

Coenzyme Q10 (CoQ10) occurs naturally in the body and possesses antioxidant and cardioprotective effects. Cardiotoxicity has emerged as a serious effect of the exposure to cadmium (Cd). This study investigated the curative potential of CoQ10 on Cd cardiotoxicity in mice, emphasizing the involvement of oxidative stress (OS) and NF-κB/NLRP3 inflammasome axis. Mice received a single intraperitoneal dose of CdCl 2 (6.5 mg/kg) and a week after, CoQ10 (100 mg/kg) was supplemented daily for 14 days. Mice that received Cd exhibited cardiac injury manifested by the elevated circulating cardiac troponin T (cTnT), CK-MB, LDH and AST. The histopathological and ultrastructural investigations supported the biochemical findings of cardiotoxicity in Cd-exposed mice. Cd administration increased cardiac MDA, NO and 8-oxodG while suppressed GSH and antioxidant enzymes. CoQ10 decreased serum CK-MB, LDH, AST and cTnT, ameliorated histopathological and ultrastructural changes in the heart of mice, decreased cardiac MDA, NO, and 8-OHdG and improved antioxidants. CoQ10 downregulated NF-κB p65, NLRP3 inflammasome, IL-1β, MCP-1, JNK1, and TGF-β in the heart of Cd-administered mice. Moreover, in silico molecular docking revealed the binding potential between CoQ10 and NF-κB, ASC1 PYD domain, NLRP3 PYD domain, MCP-1, and JNK. In conclusion, CoQ10 ameliorated Cd cardiotoxicity by preventing OS and inflammation and modulating NF-κB/NLRP3 inflammasome axis in mice. Therefore, CoQ10 exhibits potent therapeutic benefits in safeguarding cardiac tissue from the harmful consequences of exposure to Cd., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Non-alcoholic fatty liver disease (NAFLD) is a common chronic hepatic disorder characterized by hepatic lipid accumulation. This study explored the effect of betulin (BE), a terpenoid with promising antioxidant, anti-inflammatory and insulin sensitizing effects, on NAFLD induced by high fat diet (HFD). Rats received HFD and BE (15 and 30 mg/kg) for 12 weeks and blood and liver samples were collected for analyses. HFD caused hyperlipidemia, cholesterol and triglycerides accumulation in the liver, hepatocellular ballooning, fibrosis, insulin resistance (IR), lipid peroxidation (LPO), and NF-kB p65 upregulation. BE ameliorated serum and liver lipids, blood glucose and insulin, liver LPO, prevented steatosis and fibrosis, suppressed NF-kB p65 and enhanced antioxidants in HFD-fed rats. BE downregulated acetyl-CoA carboxylase (ACC1) and fatty acid synthase (FAS), and upregulated Nrf2, HO-1 and SIRT1 in the liver of HFD-fed rats. In silico investigations revealed the binding affinity of BE towards FAS, NF-kB, Keap1, HO-1 and SIRT1. In conclusion, BE attenuated HFD-induced NAFLD by ameliorating hyperlipidemia, IR, lipogenesis, liver lipid accumulation, and oxidative stress. The protective effect of BE was associated with enhanced Nrf2/HO-1 signaling and SIRT1., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier Inc. All rights reserved.)

COVID-19 is a new infectious disease caused by SARS-COV-2 virus of the coronavirus Family. The identification of drugs against this serious infection is a significant requirement due to the rapid rise in the positive cases and deaths around the world. With this concept, a molecular docking analysis for vitamins and their derivatives (28 molecules) with the active site of SARS-CoV-2 main protease was carried out. The results of molecular docking indicate that the structures with best binding energy in the binding site of the studied enzyme (lowest energy level) are observed for the compounds; Folacin, Riboflavin, and Phylloquinone oxide (Vitamin K1 oxide). A Molecular Dynamic simulation was carried out to study the binding stability for the selected vitamins with the active site of SARS-CoV-2 main protease enzyme. Molecular Dynamic shows that Phylloquinone oxide and Folacin are quite unstable in binding to SARS-CoV-2 main protease, while the Riboflavin is comparatively rigid. The higher fluctuations in Phylloquinone oxide and Folacin indicate that they may not fit very well into the binding site. As expected, the Phylloquinone oxide exhibits small number of H-bonds with protein and Folacin does not form a good interaction with protein. Riboflavin exhibits the highest number of Hydrogen bonds and forms consistent interactions with protein. Additionally, this molecule respect the conditions mentioned in Lipinski's rule and have acceptable ADMET proprieties which indicates that Riboflavin (Vitamin B2) could be interesting for the antiviral treatment of COVID-19., Competing Interests: Conflict of interest declared none. All authors read and approved the final version of manuscript., (© 2022 Elsevier B.V. All rights reserved.)

Covid-19 is an emerging infectious disease caused by coronavirus SARS-CoV-2. Due to the rapid rise in deaths resulted from this infection all around the world, the identification of drugs against this new coronavirus is an important requirement. Among the drugs that can fight this type of infection; natural products are substances that serve as sources of beneficial chemical molecules for the development of effective therapies. In this study, Camphor, Artemisinin and 14 Sumac phytochemicals were docked in the active site of SARS-CoV-2 main protease (PDB code: 6LU7). We have also performed molecular dynamic simulation at 100 ns with MM-GBSA/PBSA analysis for the structures with the best affinity in the binding site of the studied enzyme (Hinokiflavone and Myricetin) after docking calculations to consider parameters like RMSD, covariance, PCA, radius of gyration, potential energy, temperature and pressure. The result indicates that Hinokiflavone and Myricetin are the structures with best affinity and stability in the binding site of the studied enzyme and they respect the conditions mentioned in Lipinski's rule and have acceptable ADMET proprieties; so, these compounds have important pharmacokinetic properties and bioavailability, and they could have more potent antiviral treatment of COVID-19 than the other studied compounds., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Because of the fast increase in deaths due to Corona Viral Infection in majority region in the world, the detection of drugs potent of this infection is a major need. With this idea, docking study was executed on eighteen imidazole derivatives based on 7-chloro-4-aminoquinoline against novel Coronavirus (SARS-CoV-2). In this study, we carried out a docking study of these molecules in the active site of SARS-CoV-2 main protease. The result indicate that Molecules N° 3, 7 and 14 have more binding energy with SARS-CoV-2 main protease recently crystallized (pdb code 6LU7) in comparison with the other imidazole derivatives and the two drug; Chloroquine and hydroxychloroquine. Because of the best energy of interaction, these three molecules could have the most potential antiviral treatment of COVID-19 than the other studied compounds. The structures with best affinity in the binding site of the protease have more than 3 cycles and electronegative atoms in the structure. This may increase the binding affinity of these molecules because of formation of π-bonds, halogen interactions and/or Hydrogen bond interactions between compounds and the enzyme. So, compounds with more cycles and electronegative atoms could have a potent inhibition of SARS-CoV-2 main protease., (Copyright © 2020 Elsevier Inc. All rights reserved.)

A detailed description of pulled elbow is missing from standard orthopaedic text books. Recently it has been reported that the prevalence of hypermobility among children with pulled elbow is higher than that in the normal population and that pulled elbow can be considered to be a consequence of joint hypermobility. Two hundred children with pulled elbow comprising 106 girls and 94 boys (age range 3-84 months, mean age 24 months) were treated and evaluated for signs of hypermobility in a prospective study. Hypermobility of joints was noted in 17 (8.5 per cent) of children who had a pulled elbow while in the 71 children in whom there had been more than one episode, the rate of hypermobility was 8.4 per cent. Comparison of these results with a control group of 100 normal children, in whom 10 (10 per cent) exhibited hypermobility, showed no association between joint hypermobility and an increased incidence of pulled elbow. The anatomical construction of the radial head, relative plasticity of the cartilage and the immature annular ligament in young children possibly predisposes them to pulled elbow, the incidence of which is increasing in our modern physically competitive society where children are participating in a wide range of physically demanding sports activities. Pulled elbows can also occur in children with hypermobility of joints, but there is no evidence that the incidence has increased.