Investigating the impact of extracellular vesicles on mitochondrial function in human skeletal muscle cells

Background: Extracellular vesicles are a class of membrane limited vesicles that withhold the ability to firstly transport and secondly liaise with several cells such as proteins and lipids. There are 3 major classes of extracellular vesicles, those being microvesicles, apoptotic bodies and finally the most notable out the three, Exosomes. Surrounding extracellular vesicles, the main function was thought to be merely the removal of unwanted substances. However, due to its ability to cell to cell communicate, it has been hypothesised that Extracellular vesicles have a key role in both physiological and pathological mechanisms that make up bodily functions. Skeletal muscles are a huge endocrine organ, and its ability isn’t primarily related to its mechanisms found for physical movement but include acting like a storage for substrates key in regulating core body temperatures. Extracellular vesicles have additionally been questioned with playing a part in muscle regeneration as well as repair. Aim: It was to determine whether cells stimulated with Tumour necrosis factor – alpha caused an increase synthesis of extracellular vesicles and the effect the membrane limited vesicle had on skeletal muscle mitochondrial function. Method: Human skeletal muscle cells were cultured in varying concentrations of Tumour necrosis factor – alpha for either 24 or 72-hour incubations with two different growth medias. RNA, DNA and protein quantifications were carried out with Nanodrop. Changes in mitochondrial function were analysed with Seahorse XFP stress test to determine the effects extracellular vesicle release had on factors such as, non-mitochondrial respiration, maximal respiration and the key marker for muscle mitochondrial dysfunction, proton leak. Results: It was possible to determine that as the concentration of Tumour necrosis factor – alpha increased treatment on skeletal muscle cells, it did cause an increase synthesis of extracellular vesicles as a result. Through the identification of key hallmark exosomal markers (CD9 and CD81). Furthermore, RNA and DNA concentrations were altered, in some cases positively but also decreases in RNA and DNA were recorded. Regarding mitochondrial function, increases in proton leak and decreases in ATP production were produced indicating that the increase in extracellular vesicle could lead toward muscle dysfunction. However, the stimulation of extracellular vesicles didn’t completely disrupt mitochondrial function, in some cases it was seen the improve. Conclusion: Collectively, the results attained showed that Tumour necrosis factor – alpha treated skeletal muscle cells did cause an increase in synthesis for extracellular vesicle synthesis as well the release augmented mitochondrial function

Comparative ultrastructural hepatic alterations induced by free and liposome-encapsulated mefenamic acid

Mefenamic acid (MFA) is used as an anti-inflammatory, antinociceptive, and antipyretic agent for treatment of a wide range of pathological disorders. While the uncertainty of its safety and the poor oral bioavailability constitute the major limiting factors of its medical use, considerable efforts including liposomal encapsulation are needed to achieve maximum therapeutic advantages. The current work was conducted to investigate the ultrastructural alterations in the liver induced by free MFA and its liposomal preparation. Female Sprague-Dawley rats were treated with daily oral doses of either free MFA or MFA entrapped in Tween 80 inoculated liposomes at the concentration of 80 mg/kg for 28 days. Ultrathin sections were prepared from biopsies taken from the liver of each member of all animals under study and subjected to examination by transmission electron microscopy. The liver of rats that were exposed to liposomal MFA showed more ultrastructural alterations than the rats treated with the free drug. While both groups of rats demonstrated sinusoidal dilatation, Kupffer cell hyperplasia, mitochondrial damage, and nuclear alterations, rats treated with liposome-encapsulated MFA induced an increase in the multiple lysosomes formation, hepatocytic steatosis, and apoptotic activity than free MFA-treated rats. The ultrastructural findings of the present study indicate that the use of liposomal MFA induces more hepatic damage than the use of free MFA

Universal EEG Encoder for Learning Diverse Intelligent Tasks

Brain Computer Interfaces (BCI) have become very popular with Electroencephalography (EEG) being one of the most commonly used signal acquisition techniques. A major challenge in BCI studies is the individualistic analysis required for each task. Thus, task-specific feature extraction and classification are performed, which fails to generalize to other tasks with similar time-series EEG input data. To this end, we design a GRU-based universal deep encoding architecture to extract meaningful features from publicly available datasets for five diverse EEG-based classification tasks. Our network can generate task and format-independent data representation and outperform the state of the art EEGNet architecture on most experiments. We also compare our results with CNN-based, and Autoencoder networks, in turn performing local, spatial, temporal and unsupervised analysis on the data

A comprehensive review on Cosmos caudatus (ulam raja): pharmacology, ethnopharmacology, and phytochemistry

Cosmos caudatus or Ulam Raja in Malay originated from Latin America and transferred to Europe, Africa, and tropical Asia. It has been known for many traditional practices worldwide such as to rigidify bones and tone up blood circulation. The aim of this review is to summarize and discuss the association between phytochemical and pharmacological reports of C. caudatus and their traditional uses via ethnopharmacological approaches. Cosmos caudatus is a traditional medicinal plant used widely for culinary and therapeutic purposes. Phytochemical studies indicated the presence of Phenolic acids, flavonoids, tannins, sesquiterpene lactones, carbohydrates, minerals and vitamins in leaves while phenylpropanoids were in roots. Pharmacological data have been compiled for diverse activities for fresh leaves and extracts such as antihypertensive, antihyperlipidemic, antidiabetic, antimicrobial, antioxidant and antiosteoporotic. These activities experimented by in vitro and in vivo studies. Multiple C. caudatus constituents propose many potential actions in different fields such as neuroprotection, antidepression, and gastroprotection

Antinociceptive activity of methanolic extract of Muntingia calabura leaves: further elucidation of the possible mechanisms

Background: Muntingia calabura (Elaecoparceae) is a medicinal plant traditionally used, particularly, by the Peruvian people to alleviate headache and cold, pain associated with gastric ulcers or to reduce the prostate gland swelling. Following the recent establishment of antinociceptive activity of M. calabura leaf, the present study was performed to further elucidate on the possible mechanisms of antinociception involved. Methods: The methanol extract of M. calabura (MEMC) was prepared in the doses of 100, 250 and 500 mg/kg. The role of bradykinin, protein kinase C, pottasium channels, and various opioid and non-opioid receptors in modulating the extract’s antinociceptive activity was determined using several antinociceptive assays. Results are presented as Mean ± standard error of mean (SEM). The one-way ANOVA test with Dunnett's multiple comparison was used to analyze and compare the data, with P < 0.05 as the limit of significance. Results: The MEMC, at all doses, demonstrated a significant (p < 0.05) dose-dependent antinociceptive activity in both the bradykinin- and phorbol 12-myristate 13-acetate (PMA)-induced nociception. Pretreatment of the 500 mg/kg MEMC with 10 mg/kg glibenclamide (an ATP-sensitive K+ channel inhibitor), the antagonist of μ-, δ- and κ-opioid receptors (namely 10 mg/kg β-funaltrexamine, 1 mg/kg naltrindole and 1 mg/kg nor-binaltorphimine), and the non-opioid receptor antagonists (namely 3 mg/kg caffeine (a non-selective adenosinergic receptor antagonist), 0.15 mg/kg yohimbine (an α2-noradrenergic antagonist), and 1 mg/kg pindolol (a β-adrenoceptor antagonist)) significantly (p < 0.05) reversed the MEMC antinociception. However, 10 mg/kg atropine (a non-selective cholinergic receptor antagonist), 0.15 mg/kg prazosin (an α1-noradrenergic antagonist) and 20 mg/kg haloperidol (a non-selective dopaminergic antagonist) did not affect the extract's antinociception. The phytochemicals screening revealed the presence of saponins, flavonoids, tannins and triterpenes while the HPLC analysis showed the presence of flavonoid-based compounds. Conclusions: The antinociceptive activity of MEMC involved activation of the non-selective opioid (particularly the μ-, δ- and κ-opioid) and non-opioid (particularly adenosinergic, α2-noradrenergic, and β-adrenergic) receptors, modulation of the ATP-sensitive K+ channel, and inhibition of bradikinin and protein kinase C actions. The discrepancies in MEMC antinociception could be due to the presence of various phytochemicals

Heavy metal quantification of classroom dust in school environment and its impacts on children health from Rawang (Malaysia)

This study aimed to determine bioavailable heavy metal concentrations (As, Cd, Co, Cu, Cr, Ni, Pb, Zn) and their potential sources in classroom dust collected from children’s hand palms in Rawang (Malaysia). This study also aimed to determine the association between bioavailable heavy metal concentration in classroom dust and children’s respiratory symptoms. Health risk assessment (HRA) was applied to evaluate health risks (non-carcinogenic and carcinogenic) due to heavy metals in classroom dust. The mean of bioavailable heavy metal concentrations in classroom dust found on children’s hand palms was shown in the following order: Zn (1.25E + 01 μg/g) > Cu (9.59E-01 μg/g) > Ni (5.34E-01 μg/g) > Cr (4.72E-02 μg/g) > Co (2.34E-02 μg/g) > As (1.77E-02 μg/g) > Cd (9.60E-03 μg/g) > Pb (5.00E-03 μg/g). Hierarchical cluster analysis has clustered 17 sampling locations into three clusters, whereby cluster 1 (S3, S4, S6, S15) located in residential areas and near to roads exposed to vehicle emissions, cluster 2 (S10, S12, S9, S7) located near Rawang town and cluster 3 (S13, S16, S1, S2, S8, S14, S11, S17, S5) located near industrial, residential and plantation areas. Emissions from vehicles, plantations and industrial activities were found as the main sources of heavy metals in classroom dust in Rawang. There is no association found between bioavailable heavy metal concentrations and respiratory symptoms, except for Cu (OR = 0.03). Health risks (non-carcinogenic and carcinogenic risks) indicated that there are no potential non-carcinogenic and carcinogenic risks of heavy metals in classroom dust toward children health

The geranyl acetophenone tHGA attenuates human bronchial smooth muscle proliferation via inhibition of AKT phosphorylation

Increased airway smooth muscle (ASM) mass is a prominent hallmark of airway remodeling in asthma. Inhaled corticosteroids and long-acting beta2-agonists remain the mainstay of asthma therapy, however are not curative and ineffective in attenuating airway remodeling. The geranyl acetophenone 2,4,6-trihydroxy-3-geranyl acetophenone (tHGA), an in-house synthetic non-steroidal compound, attenuates airway hyperresponsiveness and remodeling in murine models of asthma. The effect of tHGA upon human ASM proliferation, migration and survival in response to growth factors was assessed and its molecular target was determined. Following serum starvation and induction with growth factors, proliferation and migration of human bronchial smooth muscle cells (hBSMCs) treated with tHGA were significantly inhibited without any significant effects upon cell survival. tHGA caused arrest of hBSMC proliferation at the G1 phase of the cell cycle with downregulation of cell cycle proteins, cyclin D1 and diminished degradation of cyclin-dependent kinase inhibitor (CKI), p27Kip1. The inhibitory effect of tHGA was demonstrated to be related to its direct inhibition of AKT phosphorylation, as well as inhibition of JNK and STAT3 signal transduction. Our findings highlight the anti-remodeling potential of this drug lead in chronic airway disease