Enzyme Activity of Natural Products on Cytochrome P450

Drug-metabolizing enzymes, particularly the cytochrome P450 (CYP450) monooxygenases, play a pivotal role in pharmacokinetics. CYP450 enzymes can be affected by various xenobiotic substrates, which will eventually be responsible for most metabolism-based herb–herb or herb–drug interactions, usually involving competition with another drug for the same enzyme binding site. Compounds from herbal or natural products are involved in many scenarios in the context of such interactions. These interactions are decisive both in drug discovery regarding the synergistic effects, and drug application regarding unwanted side effects. Herein, this review was conducted as a comprehensive compilation of the effects of herbal ingredients on CYP450 enzymes. Nearly 500 publications reporting botanicals’ effects on CYP450s were collected and analyzed. The countries focusing on this topic were summarized, the identified herbal ingredients affecting enzyme activity of CYP450s, as well as methods identifying the inhibitory/inducing effects were reviewed. Inhibitory effects of botanicals on CYP450 enzymes may contribute to synergistic effects, such as herbal formulae/prescriptions, or lead to therapeutic failure, or even increase concentrations of conventional medicines causing serious adverse events. Conducting this review may help in metabolism-based drug combination discovery, and in the evaluation of the safety profile of natural products used therapeutically.

Pyrazole Containing Anti-HIV Agents: An Update

Background: Pyrazole scaffolds have gained importance in drug discovery and development for various pharmacological activities like antiviral, antifungal, anticancer, antidepressant, anti-inflammatory, antibacterial, etc. Additionally, the pyrazole moiety has shown potent anti-HIV activity as a core heterocycle or substituted heterocycles derivatives (mono, di, tri, tetra, and fused pyrazole derivatives). To assist the development of further potential anti-HIV agents containing pyrazole nucleus, here we have summarized pyrazole containing anti-HIV compounds that have been reported by researchers all over the world for the last two decades. Objective: The present review concentrates on an assortment of pyrazole containing compounds, particularly for potential therapeutic activity against HIV. Methods: Google Scholar, Pubmed, and SciFinder were searched databases with ‘‘pyrazol’’ keywords. Further, the year of publication and keywords ‘‘Anti-HIV’’ filter was applied to obtain relevant reported literature for anti-HIV agents containing pyrazole as a core or substituted derivatives. Results: This review article has shown the comprehensive compilation of 220 compounds containing pyrazole nucleus and possessing anti-HIV activity by sorting approximately 40 research articles from 2001 to date. 1-(4-Benzoylpiperazin-1-yl)-2-(4-fluoro-7-(1H-pyrazol-3-yl)-1H-pyrrolo[2,3-c]pyridin-3-yl)ethane-1,2-dione (13), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-fluoro-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (31), 3-(3-(2-(4-benzoylpiperazin-1-yl)-2-oxoacetyl)-4-fluoro-1H-pyrrolo[2,3-c]pyridin-7-yl)-1H-pyrazole-5-carboxamide (88), 3-cyanophenoxypyrazole derivative (130), and 4-(4-chlorophenyl)-5-(4-methyl-5-((4-nitrophenyl)diazenyl)thiazol-2-yl)-3-phenyl-5,6-dihydro-4H-pyrazolo[4,3-d]isoxazole (178) were the most potent mono-, di-, tri-, tetra-substituted, and fused pyrazole derivatives, respectively, which have shown potent anti-HIV activity among all the described derivatives as compared with standard anti-HIV drugs. Conclusion: This review article provides an overview of the potential therapeutic activity of pyrazole derivatives against HIV that will be helpful for designing pyrazole containing compounds for anti-HIV activity.

Mouse Models of Osteoarthritis: A Summary of Models and Outcomes Assessment

Osteoarthritis (OA) is a multidimensional health problem and a common chronic disease. It has a substantial impact onpatient quality of life and is a common cause of pain and mobility issues in older adults. The functional limitations, lack of curative treatments, and cost to society all demonstrate the need for translational and clinical research. The use of OA models in mice is important for achieving a better understanding of the disease. Models with clinical relevance are needed to achieve 2 main goals: to assess the impact of the OA disease (pain and function) and to study the efficacy of potential treatments. However, few OA models include practical strategies for functional assessment of the mice. OA signs in mice incorporate complex interrelations between pain and dysfunction. The current review provides a comprehensive compilation of mousemodels of OA and animal evaluations that include static and dynamic clinical assessment of the mice, merging evaluationof pain and function by using automatic and noninvasive techniques. These new techniques allow simultaneous recordingof spontaneous activity from thousands of home cages and also monitor environment conditions. Technologies such as videographyand computational approaches can also be used to improve pain assessment in rodents but these new tools must first be validated experimentally. An example of a new tool is the digital ventilated cage, which is an automated home-cage monitor that records spontaneous activity in the cages.

India Indenting Eurasia: A Brief Review and New Data from the Yongping Basin on the SE Tibetan Plateau

Successive indentations of Eurasia by India have led to the Tibet-Himalaya E–W orthogonal collision belt and the SE Tibetan Plateau N–S oblique collision belt along the frontal and eastern edges of the indenter, respectively. The belts exhibit distinctive lithospheric structures and tectonic evolutions. A comprehensive compilation of available geological and geophysical data reveals two sudden tectonic transitions in the early Eocene and the earliest Miocene, respectively, of the tectonic evolution of the orthogonal belt. Synthesizing geological and geochronological data helps us to suggest a NEE–SWW trending, ~450 km-long, ~250 km-wide magmatic zone in SE Tibet, which separates the oblique collision belt (eastern and SE Tibet) into three segments of distinctive seismic structures including the mantle and crust anisotropies. The newly identified Yongping basin is located in the central part of the magmatic zone. Geochronological and thermochronological data demonstrate that (1) this basin and the magmatic zone started to form at ~48 Ma likely due to NNW–SSE lithosphere stretching according to the spatial coincidence of the concentrated mantle-sourced igneous rocks on the surface with the seismic anomalies at depth; and (2) its fills was shortened in the E–W direction since ~23 Ma. These two dates correspond to the onset of the first and second tectonic transitions of the orthogonal collision belt. As such, both the orthogonal and oblique belts share a single time framework of their tectonic evolution. By synthesizing geological and geophysical data of both collision belts, the indenting process can be divided into three stages separated by two tectonic transitions. Continent–continent collision as a piston took place exclusively during the second stage. During the other two stages, the India lithosphere underthrust beneath Eurasia.

Introduction to the volume, and definition and use of the term ‘tectono-sedimentary element’

The present volume is rooted in a map of sedimentary successions of the Arctic Region by Grantz et al. (2011), and contains a brief, but comprehensive compilation of geological and geophysical data characterizing all significant sedimentary successions in the Arctic, which cover 57% of the polar area north of 64°N. Two main goals have been designated: (i) to provide, based on the present-day knowledge and data, a characterization of all Arctic sedimentary successions (or sedimentary accumulations), and (ii) to supply a snapshot of hydrocarbon-related exploration in the Arctic at the end of the second decade of this millennium. To achieve these goals, we represent sedimentary successions as consisting of one or several “Tectono-Sedimentary Elements” (TSE). This concept allows delineation, mapping, and characterization of 9 categories of TSEs based of main tectonic regimes that formed accommodation space.A TSE characterization template has been developed as an efficient method of organising and presenting the most important information about stratigraphy, structure, and petroleum geology of a TSE, including most significant exploration facts. This organizational architecture is the backbone of the volume and is a key feature that distinguishes it from other similar works about the sedimentary basins.

A compilation and characterisation of lithics in kimberlite and common maar-diatremes and tephra ring deposits

Maar-diatreme volcanoes are the second-most common type on land, occurring in volcanic fields within all major tectonic environments. Their deposits typically contain an abundance of lithic fragments quarried from the substrate, and many contain large, deep-sourced lithic fragments that were erupted to the surface. Primary volcaniclastic deposits fill the diatreme structure formed during eruption. There is negligible inelastic deformation of diatreme-adjacent country rock, indicating that country rock is removed to create the diatreme structures, either by being shifting downward below observable levels, ejected upward to contribute to surficial deposits, or dissolved and hidden in magma erupted or intruded at depth. No previous study has systematically reviewed and analysed the reported lithic fragments of maar-diatreme systems. We present a comprehensive compilation from published work of lithic characteristics in maar ejecta rings and in diatreme deposits of both common and kimberlite maar-diatremes. For maar-diatremes and their tephra ring deposits, we find no correlations among lithic clast sizes, shapes, depositional sites, and excavation depths. This is difficult to reconcile with models involving systematic diatreme deepening coupled with tephra-ring growth, but consistent with those involving chaotic explosions and mixing. Larger amounts of data are needed to further examine how these types of volcanoes operate.

Critical review of the Withania somnifera (L.) Dunal: ethnobotany, pharmacological efficacy, and commercialization significance in Africa

Background Withania somnifera (L.) Dunal (W. somnifera) is a herb commonly known by its English name as Winter Cherry. Africa is indigenous to many medicinal plants and natural products. However, there is inadequate documentation of medicinal plants, including W. somnifera, in Africa. There is, therefore, a need for a comprehensive compilation of research outcomes of this reviewed plant as used in traditional medicine in different regions of Africa. Methodology Scientific articles and publications were scooped and sourced from high-impact factor journals and filtered with relevant keywords on W. somnifera. Scientific databases, including GBIF, PubMed, NCBI, Google Scholar, Research Gate, Science Direct, SciFinder, and Web of Science, were accessed to identify the most influential articles and recent breakthroughs published on the contexts of ethnography, ethnomedicinal uses, phytochemistry, pharmacology, and commercialization of W. somnifera. Results This critical review covers the W. somnifera ethnography, phytochemistry, and ethnomedicinal usage to demonstrate the use of the plant in Africa and elsewhere to prevent or alleviate several pathophysiological conditions, including cardiovascular, neurodegenerative, reproductive impotence, as well as other chronic diseases. Conclusion W. somnifera is reportedly safe for administration in ethnomedicine as several research outcomes confirmed its safety status. The significance of commercializing this plant in Africa for drug development is herein thoroughly covered to provide the much-needed highlights towards its cultivations economic benefit to Africa.

South Africa’s contribution in the field of Forensic Odontology - A textbook review

This textbook represents an up-to-date, comprehensive compilation of the field of Forensic Odontology. The chapters have been uniquely structured to take the reader through all aspects of this discipline in a methodical and logical approach. Authors for each section were carefully selected as being internationally recognised experts and renowned amongst their peers in their particular field of Forensic Odontology. The material in this textbook is presented in a manner that is both interesting and clear for novices in the discipline, while at the same time offering highly informative, cutting-edge information for experts practising Forensic Odontology. The book begins with a chronology of the origin of Forensic Odontology dating back to 1477, using intriguing real-life cases to set the theme for the rest of the book.

Indicators for Public Mental Health: A Scoping Review

Background: To monitor population mental health, the identification of relevant indicators is pivotal. This scoping review provides a comprehensive overview of current indicators representing the various fields of public mental health core topics. It was conducted as a first step to build up a Mental Health Surveillance for Germany.Methods: We conducted a systematic MEDLINE search via PubMed. This search was supplemented by an extensive examination of the websites of relevant national as well as international institutions in the context of public mental health and an additional internet search via Google. To structure the data, an expert-based focus group identified superordinate topics most relevant to public mental health to which the identified indicators could be assigned to. Finally, the indicator set was screened for duplicates and appropriate content to arrive at a final set.Results: Within the various search strategies, we identified 13.811 records. Of these records, a total of 365 records were processed for indicator extraction. The extracted indicators were then assigned to 14 topics most relevant to public mental health as identified by the expert-based focus group. After the exclusion of duplicates and those indicators not meeting criteria of specificity and target group, the final set consisted of 192 indicators.Conclusion: The presented indicator set provides guidance in the field of current concepts in public mental health monitoring. As a comprehensive compilation, it may serve as basis for future surveillance efforts, which can be adjusted and condensed depending on the particular monitoring focus. Our work provides insights into established indicators included in former surveillance work as well as recent, not yet included indicators reflecting current developments in the field. Since our compilation mainly concludes indicators related to mental health in adults, it should be complemented with indicators specific to children and adolescents. Furthermore, our review revealed that indicators on mental health promotion and prevention are underrepresented in current literature of public mental health and should hence be focused on within future research and surveillance.

Regulation of ER Composition and Extent, and Putative Action in Protein Networks by ER/NE Protein TMEM147

Nuclear envelope (NE) and endoplasmic reticulum (ER) collaborate to control a multitude of nuclear and cytoplasmic actions. In this context, the transmembrane protein TMEM147 localizes to both NE and ER, and through direct and indirect interactions regulates processes as varied as production and transport of multipass membrane proteins, neuronal signaling, nuclear-shape, lamina and chromatin dynamics and cholesterol synthesis. Aiming to delineate the emerging multifunctionality of TMEM147 more comprehensively, we set as objectives, first, to assess potentially more fundamental effects of TMEM147 on the ER and, second, to identify significantly TMEM147-associated cell-wide protein networks and pathways. Quantifying curved and flat ER markers RTN4 and CLIMP63/CKAP4, respectively, we found that TMEM147 silencing causes area and intensity increases for both RTN4 and CLIMP63, and the ER in general, with a profound shift toward flat areas, concurrent with reduction in DNA condensation. Protein network and pathway analyses based on comprehensive compilation of TMEM147 interactors, targets and co-factors then served to manifest novel and established roles for TMEM147. Thus, algorithmically simplified significant pathways reflect TMEM147 function in ribosome binding, oxidoreductase activity, G protein-coupled receptor activity and transmembrane transport, while analysis of protein factors and networks identifies hub proteins and corresponding pathways as potential targets of TMEM147 action and of future functional studies.