Nordihydroguaiaretic Acid from Creosote Bush (Larrea tridentata) Mitigates 12-O-Tetradecanoylphorbol-13-Acetate-Induced Inflammatory and Oxidative Stress Responses of Tumor Promotion Cascade in Mouse Skin

Nordihydroguaiaretic acid (NDGA) is a phenolic antioxidant found in the leaves and twigs of the evergreen desert shrub, Larrea tridentata (Sesse and Moc. ex DC) Coville (creosote bush). It has a long history of traditional medicinal use by the Native Americans and Mexicans. The modulatory effects of topically applied NDGA was studied on acute inflammatory and oxidative stress responses in mouse skin induced by stage I tumor promoting agent, 12-O-tetradecanoylphorbol-13-acetate (TPA). Double TPA treatment adversely altered many of the marker responses of stage I skin tumor promotion cascade. Pretreatment of NDGA in TPA-treated mice mitigated cutaneous lipid peroxidation and inhibited production of hydrogen peroxide. NDGA treatment also restored reduced glutathione level and activities of antioxidant enzymes. Elevated activities of myeloperoxidase, xanthine oxidase and skin edema formation in TPA-treated mice were also lowered by NDGA indicating a restrained inflammatory response. Furthermore, results of histological study demonstrated inhibitory effect of NDGA on cellular inflammatory responses. This study provides a direct evidence of antioxidative and anti-inflammatory properties of NDGA against TPA-induced cutaneous inflammation and oxidative stress corroborating its chemopreventive potential against skin cancer

Pharmacological insights and prediction of lead bioactive isolates of Dita bark through experimental and computer-aided mechanism.

Dita bark (Alstonia scholaris (L.) R. Br.) is an ethnomedicine used for the management of various ailments. This study aimed to investigate the biological properties of methanol extract of A. scholaris bark (MEAS), through in vivo, in vitro and in silico approaches alongside its phytochemical profiling. Identification and nature of the bioactive secondary metabolites were studied by the established qualitative tests and GC-MS analysis. The antidepressant activity was determined by forced swimming test (FST) and tail suspension test (TST) in mice. The anti-inflammatory and thrombolytic effect was evaluated using inhibition of protein denaturation technique and clot lysis technique, respectively. Besides, computational studies of the isolated compounds and ADME/T analysis were performed by Schrodinger-Maestro (v11.1) software, and PASS prediction was conducted through PASS online tools. The GC-MS analysis revealed the presence of several secondary metabolites in MEAS. Treatment with MEAS revealed a significant reduction of immobility time in a dose-dependent manner in FST and TST. Besides, MEAS showed substantial anti-inflammatory effects at the higher dose (400 μg/mL) as well as revealed notable clot lysis effect as compared to control. In the case of computer-aided investigation, all compounds meet the condition of Lipinski's rule of five. PASS study also predicted for all compounds, and among these safe compound furazan-3-amine showed the most spontaneous binding energy for both antidepressant and thrombolytic activities, as well as 5-dimethylamino-6 azauracil, found promising for anti-inflammatory activity. Taken together, the investigation concludes that MEAS can be a potent source of antidepressant, anti-inflammatory, and thrombolytic agents

A General Infrastructure for Communication between Petri Modules

Modularization provides many benefits to real-world discrete-event systems, such as flexibility, comprehensibility, and robustness. Davidrajuh[2] presents a new modular Petri net with well-defined Petri modules. With the new modular Petri net, distributed Petri modules are designed. The modules are hosted on different computers that are geographically kept apart but can communicate over the network. The distributed Petri modules approach minimizes the simulation time; reduces the state space size and other complexities. The distributed Petri modules are implemented in the software known as Generalpurpose Petri Net Simulator (GPenSIM). In this thesis, a network layer is implemented into GPenSIM to allow the distributed modules to communicate. Two distributed systems are designed and implemented in GPenSIM, and MATLAB TCP/IP socket communication is used to develop the network. Implementing a network layer into GPenSIM allows simulation that is more realistic and easy to analyze the performance

Ichthyosis vulgaris and pycnodysostosis: An unusual occurrence

Pycnodysostosis is a rare autosomal recessive disorder whose generesponsible for this phenotype (CTSK), mapped to human chromosome1q21, code for the enzyme cathepsin K, a lysosomal cysteineprotease; with an estimated incidence of 1.7 per 1 million births. This clinical entity includes micromelic dwarfism, increased radiological bone density, dysplasia of the skull, acro-osteolysis, straightening of the mandibular angle and in some cases, dysplasia of the acromial end of the clavicle. Oral and maxillo-facial manifestations of this disease are very clear. Herein we reported a case of pycnodysostosis, showing short stature with widening of the sutures, unfused anterior and posterior fontanelles, crowding of teeth with dental caries and typical radiological features associated with ichthyosis vulgaris and palmoplantar keratoderma

Effect of an Integrated Physiotherapy Protocol on Knee Osteoarthritis Patients: A Preliminary Study

Background: Exercise therapy can potentially relieve symptoms and improve functional status of the knee osteoarthritis population. Despite the proved practical benefits, there is no standard, comprehensive physiotherapeutic protocol available targeting the physical and physiological impairment cluster associated with disease. Osteoarthritis is a whole joint disease, affecting joint cartilage, ligaments, menisci and joint associated muscles, from variable pathophysiological processes. Hence, there is a need to develop a physiotherapy protocol to address the multi-structural physical, physiological and functional impairments associated with the disease. Objective: The objective of the present study is to evaluate the efficacy of designed, therapist supervised, patient education, progressive resistance exercises, passive stretching exercises, soft tissue manipulation, muscle energy technique, Maitland mobilization, aerobic exercise, and neuromuscular training physiotherapy protocol on pain, disability, balance, and physical functional performance in knee osteoarthritis patients. Methodology: The preliminary study was conducted on a (n = 60) sample of convenience. The samples were randomly allocated into two study groups, intervention, and control group. The control group was advised on a basic home program. On the other hand, the treatment of the intervention group was designed with a therapist supervised Physiotherapy Protocol. The outcome variables studied were the Visual Analogue Scale, Modified WOMAC Scale, Timed Up and Go Test, Functional Reach Test, 40 m Fast Paced Walk Test, Stair Climb Test, 30 s Chair Stand Test. Results: The results of the study revealed a significant improvement among most of the studied outcome measures in the intervention group, hence the designed supervised physiotherapy protocol was found effective in relieving multiple physiological impairments associated with this whole joint disease

Synthesis and HDAC1 inhibitory activity of a novel series of coumarin-based amide derivatives for treatment of cancer

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Wastewater genomic surveillance tracks the spread of the SARS-CoV-2 Omicron variant across England

Background Many countries have moved into a new stage of managing the SARS-CoV-2 pandemic with minimal restrictions and reduced testing in the population, leading to reduced genomic surveillance of virus variants in individuals. Wastewater-based epidemiology (WBE) can provide an alternative means of tracking virus variants in the population but is lacking verifications of its comparability to individual testing data. Methods We analysed more than 19,000 samples from 524 wastewater sites across England at least twice a week between November 2021 and February 2022, capturing sewage from &gt;70% of the English population. We used amplicon-based sequencing and the phylogeny based de-mixing tool Freyja to estimate SARS-CoV-2 variant frequencies and compared these to the variant dynamics observed in individual testing data from clinical and community settings. Findings We show that wastewater data can reconstruct the spread of the Omicron variant across England since November 2021 in close detail and aligns closely with epidemiological estimates from individual testing data. We also show the temporal and spatial spread of Omicron within London. Our wastewater data further reliably track the transition between Omicron subvariants BA1 and BA2 in February 2022 at regional and national levels. Interpretation Our demonstration that WBE can track the fast-paced dynamics of SARS-CoV-2 variant frequencies at a national scale and closely match individual testing data in time shows that WBE can reliably fill the monitoring gap left by reduced individual testing in a more affordable way.</jats:p