Engineering a microbiosphere to clean up the ocean – inspiration from the plastisphere

Plastic is a ubiquitous material that has become an essential part of our lives. More than one hundred million tons of plastic has accumulated in the world’s oceans as a result of poor waste management. This plastic waste gradually fragments into smaller pieces known as microplastics and nanoplastics. These small plastic particles can cause significant damage to marine ecosystems, and negatively impact human health. According to a recent review of international patents, the majority of ocean-cleaning inventions are limited to microplastics larger than 20 μm. Furthermore, such technologies are ineffective for nanoplastics, which measure less than 1000 nm, or even fibrous plastics. Alternative solutions need to be considered for the large-scale in situ removal of microplastics and nanoplastics from the ocean. In this perspective, we present the concept of engineering a microbial ecosystem, which we term the microbiosphere. The concept is based on key observations that have been made for natural plastic-based ecosystems known as plastispheres. These observations relate to the solid support material, self-sustainability, attachment to plastic, degradation of plastic, and risk of pathogenicity. Inspiration can be taken from the plastisphere whereby a novel microbial ecosystem could be designed and engineered as a bioremediation tool to rid the ocean of micro- and nanoplastics. Such an engineered system could outcompete pathogens for marine plastic waste and potentially reduce the risk of infectious diseases

Descriptive Analysis of Physical Activity Initiatives for Health Promotion in Saudi Arabia

Background: Although the benefits of physical activity are well acknowledged, a high percentage of Saudi population, especially females, remain essentially physically inactive. Getting inactive people to start participating in physical activity and to keep exercising remains a great challenge. Physical activity initiatives in the country have not been previously documented. Therefore, the aim of this article was to provide a narrative review of the physical activity initiatives and discusses influencing factors.Methods: Publically-available physical activity initiatives conducted before June 2018 were searched through the web or they were obtained straight from the organization themselves. The search focus was on any initiative aimed to promote physical activity and mass sports participation and encourage people to adopt active living habit.Results: Numerous initiatives aimed at promoting physical activity existed in Saudi Arabia. However, a common attribute of these initiatives is that they were fragmented, short term attempts, and lacked a coordinating body. The majority of the physical activity initiatives also lacked objective evaluations of their outcomes. It was clear that more physical activity opportunity must be provided for Saudi girls, women, and elderly. There is a need for establishing a national policy encouraging active living and discouraging sedentary lifestyle with contributions from all involved parties.Conclusions: Based on the available evidences, more intensified efforts toward promoting physical activity and reducing sedentary behaviors among Saudi population are needed in order to reduce the risks of NCD's

The Meisenheimer complex as a paradigm in drug discovery: reversible covalent inhibition through C67 of the ATP binding site of PLK1

The polo kinase family are important oncology targets that act in regulating entry into and progression through mitosis. Structure-guided discovery of a new class of inhibitors of Polo-like kinase 1 (PLK1) catalytic activity that interact with Cys67 of the ATP binding site is described. Compounds containing the benzothiazole N-oxide scaffold not only bind covalently to this residue, but are reversible inhibitors through the formation of Meisenheimer complexes. This mechanism of kinase inhibition results in compounds that can target PLK1 with high selectivity, while avoiding issues with irreversible covalent binding and interaction with other thiol-containing molecules in the cell. Due to renewed interest in covalent drugs and the plethora of potential drug targets, these represent prototypes for the design of kinase inhibitory compounds that achieve high specificity through covalent interaction and yet still bind reversibly to the ATP cleft, a strategy that could be applied to avoid issues with conventional covalent binders

5-deazaflavin derivatives as inhibitors of p53 ubiquitination by HDM2

Based on previous reports of certain 5-deazaflavin derivatives being capable of activating the tumour suppressor p53 in cancer cells through inhibition of the p53-specific ubiquitin E3 ligase HDM2, we have conducted an structure–activity relationship (SAR) analysis through systematic modification of the 5-deazaflavin template. This analysis shows that HDM2-inhibitory activity depends on a combination of factors. The most active compounds (e.g., 15) contain a trifluoromethyl or chloro substituent at the deazaflavin C9 position and this activity depends to a large extent on the presence of at least one additional halogen or methyl substituent of the phenyl group at N10. Our SAR results, in combination with the HDM2 RING domain receptor recognition model we present, form the basis for the design of drug-like and potent activators of p53 for potential cancer therapy

Attenuating Muscle Damage Biomarkers and Muscle Soreness After an Exercise-Induced Muscle Damage with Branched-Chain Amino Acid (BCAA) Supplementation:A Systematic Review and Meta-analysis with Meta-regression

Background: Branched-chain amino acid (BCAA) supplementation is one of the most popular strategies used by the general population and athletes to reduce muscle soreness and accelerate the recovery process of muscle damage biomarkers after an intense exercise or training session. Objectives: This systematic review and meta-analysis investigated the effects of BCAA supplementation on muscle damage biomarkers and muscle soreness after exercise-induced muscle damage (EIMD). Methods: The systematic literature search for randomized controlled trials was conducted using seven databases, up to September 13th, 2022. The eligibility criteria for selecting studies were as follows: studies performed on healthy active participants, using BCAA at least once, controlled with a placebo or control group, performing resistance or endurance exercises, and followed up at least once post-EIMD. The methodological quality of the studies was assessed using the “SIGN RCT checklist”. Random-effects meta-analyses were processed to compute the standardized mean difference (Hedges’ g). Meta-regression analyses were completed with daily and total dosage and supplementation as continuous moderator variables. Results: Of the 18 studies included in this meta-analysis, 13 were of high quality and five were of acceptable quality. Our results revealed BCAA supplementation elicits a significant effect on reducing creatine kinase (CK) levels immediately (g = − 0.44; p = 0.006) and 72 h (g = − 0.99; p = 0.002), but not 24 h, 48 h, and 96 h post-EIMD. Additionally, a significant effect on delayed onset of muscle soreness (DOMS) was identified at 24 h (g = − 1.34; p < 0.001), 48 h (g = − 1.75; p < 0.001), 72 h (g = − 1.82; p < 0.001), and 96 h (g = − 0.82; p = 0.008), but not immediately post-EIMD. No significant effect was found on lactate dehydrogenase (LDH) levels at any time point. Meta-regression indicated higher daily and total dosages of BCAA, and longer supplementation periods were related to the largest beneficial effects on CK (total dosage and supplementation period) at 48 h, and on DOMS at 24 h (only daily dosage). Conclusion: The overall effects of BCAA supplementation could be considered useful for lowering CK and DOMS after EIMD, but not LDH. The longer supplementation period prior to the EIMD could be more effective for CK and DOMS reduction

Attenuating muscle damage biomarkers and muscle soreness after an exercise-induced muscle damage with Branched-Chain Amino Acid (BCAA) supplementation : a systematic review and meta-analysis with meta-regression

Background: Branched-chain amino acid (BCAA) supplementation is one of the most popular strategies used by the general population and athletes to reduce muscle soreness and accelerate the recovery process of muscle damage biomarkers after an intense exercise or training session. Objectives: This systematic review and meta-analysis investigated the effects of BCAA supplementation on muscle damage biomarkers and muscle soreness after exercise-induced muscle damage (EIMD). Methods: The systematic literature search for randomized controlled trials was conducted using seven databases, up to September 13th, 2022. The eligibility criteria for selecting studies were as follows: studies performed on healthy active participants, using BCAA at least once, controlled with a placebo or control group, performing resistance or endurance exercises, and followed up at least once post-EIMD. The methodological quality of the studies was assessed using the “SIGN RCT checklist”. Random-effects meta-analyses were processed to compute the standardized mean difference (Hedges’ g). Meta-regression analyses were completed with daily and total dosage and supplementation as continuous moderator variables. Results: Of the 18 studies included in this meta-analysis, 13 were of high quality and five were of acceptable quality. Our results revealed BCAA supplementation elicits a significant effect on reducing creatine kinase (CK) levels immediately (g = − 0.44; p = 0.006) and 72 h (g = − 0.99; p = 0.002), but not 24 h, 48 h, and 96 h post-EIMD. Additionally, a significant effect on delayed onset of muscle soreness (DOMS) was identified at 24 h (g = − 1.34; p < 0.001), 48 h (g = − 1.75; p < 0.001), 72 h (g = − 1.82; p < 0.001), and 96 h (g = − 0.82; p = 0.008), but not immediately post-EIMD. No significant effect was found on lactate dehydrogenase (LDH) levels at any time point. Meta-regression indicated higher daily and total dosages of BCAA, and longer supplementation periods were related to the largest beneficial effects on CK (total dosage and supplementation period) at 48 h, and on DOMS at 24 h (only daily dosage). Conclusion: The overall effects of BCAA supplementation could be considered useful for lowering CK and DOMS after EIMD, but not LDH. The longer supplementation period prior to the EIMD could be more effective for CK and DOMS reduction

Arabic translation, cultural adaptation, and pre-testing of neighborhood environment walkability scale for adults-abbreviated (NEWS-A): Arabic NEWS-A

BackgroundImproving neighborhood walkability is critical for sustainable and livable urban development and is associated with increased physical activity. The Neighborhood Environment Walkability Scale-Abbreviated (NEWS-A) is a tool for assessing neighborhood walkability among adults. Currently, no Arabic version is available for this important walkability scale.ObjectiveTo translate the NEWS-A to Arabic, culturally adapt, and pre-test it for adults.MethodsThe NEWS-A was translated and culturally adapted using Cross-cultural Survey Guidelines and then pre-tested using 65 households selected randomly from the neighborhoods of three districts in Riyadh. After answering the survey, 55 participants took part in a semi-structured cognitive interview, which sought their understanding of the words in the Arabic questionnaire, the clarity of each item, and their suggestions for improvement.ResultsTranslation and adaptation of NEWS-A to Arabic resulted in adding two items (mosque and healthcare center) to section B of the scale (stores, facilities, and other things in your neighborhood) and one related item to section C (access to services). The total individual items became 57 instead of the original 54 items in the English version. Also, we added “ATM machine” to item 14 (Bank/credit union) in section B. In addition, the overall results of the cognitive interview showed that most of the participants understood the intended meaning of the questionnaire (99.5%). Further, 99.8% of the respondents stated that the items were not difficult to comprehend, while 100% of the sample indicated that the sentences were comfortable and not sensitive to them.ConclusionTranslating, adapting, and pre-testing the NEWS-A resulted in retaining all the original items and adding three additional items. The Arabic NEWS-A provides an important tool for future research on neighborhood environment walkability among adults

Discovery and Characterization of 2-Anilino-4- (Thiazol-5-yl)Pyrimidine Transcriptional CDK Inhibitors as Anticancer Agents

The main difficulty in the development of ATP antagonist kinase inhibitors is target specificity, since the ATP-binding motif is present in many proteins. We introduce a strategy that has allowed us to identify compounds from a kinase inhibitor library that block the cyclin-dependent kinases responsible for regulating transcription, i.e., CDK7 and especially CDK9. The screening cascade employs cellular phenotypic assays based on mitotic index and nuclear p53 protein accumulation. This permitted us to classify compounds into transcriptional, cell cycle, and mitotic inhibitor groups. We describe the characterization of the transcriptional inhibitor class in terms of kinase inhibition profile, cellular mode of action, and selectivity for transformed cells. A structural selectivity rationale was used to optimize potency and biopharmaceutical properties and led to the development of a transcriptional inhibitor, 3,4-dimethyl-5-[2-(4-piperazin-1-yl-phenylamino)-pyrimidin-4-yl]-3H-thiazol-2-one, with anticancer activity in animal models