In silico studies on the anti-acne potential of Garcinia mangostana xanthones and benzophenones.

Garcinia mangostana fruits are used traditionally for inflammatory skin conditions, including acne. In this study, an in silico approach was employed to predict the interactions of G. mangostana xanthones and benzophenones with three proteins involved in the pathogenicity of acne, namely the human JNK1, Cutibacterium acnes KAS III and exo-ß-1,4-mannosidase. Molecular docking analysis was performed using Autodock Vina. The highest docking scores and size-independent ligand efficiency values towards JNK1, C. acnes KAS III and exo-ß-1,4-mannosidase were obtained for garcinoxanthone T, gentisein/2,4,6,3',5'-pentahydroxybenzophenone and mangostanaxanthone VI, respectively. To the best of our knowledge, this is the first report of the potential of xanthones and benzophenones to interact with C. acnes KAS III. Molecular dynamics simulations using GROMACS indicated that the JNK1-garcinoxanthone T complex had the highest stability of all ligand-protein complexes, with a high number of hydrogen bonds predicted to form between this ligand and its target. Petra/Osiris/Molinspiration (POM) analysis was also conducted to determine pharmacophore sites and predict the molecular properties of ligands influencing ADMET. All ligands, except for mangostanaxanthone VI, showed good membrane permeability. Garcinoxanthone T, gentisein and 2,4,6,3',5'-pentahydroxybenzophenone were identified as the most promising compounds to explore further, including in experimental studies, for their anti-acne potential.

Exploring the link between ACEs and opioid use: A systematic review.

OBJECTIVE: To review the current literature surrounding the relationship between adverse childhood experiences (ACEs) and opioid use disorder (OUD) to guide clinical identification of high-risk individuals and assess treatment implications. DESIGN: A PubMed search was conducted from the year 2000 to 2022 using a series of primary and secondary search terms. A total of 21,524 unique results were screened for relevancy to ACEs and OUDs. After excluding unrelated articles, a total of 48 articles were included in this systematic review. RESULTS: Increased frequency of ACEs was directly related to increased risk of OUD and lower onset age. ACEs were also associated with OUD severity. ACEs linked to OUD included childhood neglect, emotional abuse, physical abuse, and sexual abuse. Additionally, dysfunctional childhood home environment, female gender, and psychiatric/behavioral comorbidities increased the risk of OUD, while resilience was found to be a protective factor. Multiple biochemical markers were associated with both ACEs and OUD. CONCLUSIONS: Children experiencing multiple ACEs should be the target of preventative intervention by medical professionals. Clinicians should include ACEs in their opioid misuse risk assessment. High incidence of co-occurring psychiatric/behavioral disorders provides multiple treatment avenues for patients with OUD. Resilience, along with being therapy target, should be fostered early in the life course. Incorporation of family members may improve opioid abuse treatment outcomes. Future research should focus on interventions interrupting the progression of ACEs to OUD along with proposed biochemical pathways.

To Predict, Prevent, and Manage Post-Traumatic Stress Disorder (PTSD): A Review of Pathophysiology, Treatment, and Biomarkers.

Post-traumatic stress disorder (PTSD) can become a chronic and severely disabling condition resulting in a reduced quality of life and increased economic burden. The disorder is directly related to exposure to a traumatic event, e.g., a real or threatened injury, death, or sexual assault. Extensive research has been done on the neurobiological alterations underlying the disorder and its related phenotypes, revealing brain circuit disruption, neurotransmitter dysregulation, and hypothalamic-pituitary-adrenal (HPA) axis dysfunction. Psychotherapy remains the first-line treatment option for PTSD given its good efficacy, although pharmacotherapy can also be used as a stand-alone or in combination with psychotherapy. In order to reduce the prevalence and burden of the disorder, multilevel models of prevention have been developed to detect the disorder as early as possible and to reduce morbidity in those with established diseases. Despite the clinical grounds of diagnosis, attention is increasing to the discovery of reliable biomarkers that can predict susceptibility, aid diagnosis, or monitor treatment. Several potential biomarkers have been linked with pathophysiological changes related to PTSD, encouraging further research to identify actionable targets. This review highlights the current literature regarding the pathophysiology, disease development models, treatment modalities, and preventive models from a public health perspective, and discusses the current state of biomarker research.

Endothelial progenitor cell-derived small extracellular vesicles for myocardial angiogenesis and revascularization.

Background: Endothelial progenitor cells (EPCs) have been well-studied for their differentiation potential and paracrine activity in vitro and in experimental animal studies. EPCs are the precursors of endothelial cells (ECs) and a rich source of pro-angiogenic factors, and hence, possess enormous potential to treat ischemic heart through myocardial angiogenesis. Their proven safety and efficacy observed during the pre-clinical and clinical studies have portrayed them as a near ideal cell type for cell-based therapy of ischemic heart disease.In response to the chemical cues from the ischemic heart, EPCs from the bone marrow and peripheral circulation home-in to the ischemic myocardium and participate in the intrinsic repair process at the molecular and cellular levels through paracrine activity and EC differentiation. EPCs also release small extracellular vesicles (sEVs) loaded with bioactive molecules as part of their paracrine activity for intercellular communication to participate in the reparative process in the heart. Aim: This literature review is based on the published data regarding the characteristic features of EPC-derived sEVs and their proteomic and genomic payload, besides facilitating safe and effective repair of the ischemic myocardium. In light of the encouraging published data, translational and clinical assessment of EPC-derived sEVs is warranted. We report the recent experimental animal studies and their findings using EPC-derived sEVs on cardiac angiogenesis and preservation of cardiac function. Relevance for Patients: With the promising results from pre-clinical studies, clinical trials should be conducted to assess the clinical utility of EPC-derived sEVs in the treatment of the ischemic myocardium.

A Public Health Perspective of Post-Traumatic Stress Disorder.

Trauma exposure is one of the most important and prevalent risk factors for mental and physical ill-health. Prolonged or excessive stress exposure increases the risk of a wide variety of mental and physical symptoms, resulting in a condition known as post-traumatic stress disorder (PTSD). The diagnosis might be challenging due to the complex pathophysiology and co-existence with other mental disorders. The prime factor for PTSD development is exposure to a stressor, which variably, along with peritraumatic conditions, affects disease progression and severity. Additionally, many factors are thought to influence the response to the stressor, and hence reshape the natural history and course of the disease. With sufficient knowledge about the disease, preventive and intervenient methods can be implemented to improve the quality of life of the patients and to limit both the medical and economic burden of the disease. This literature review provides a highlight of up-to-date literature on traumatic stress, with a focus on causes or triggers of stress, factors that influence response to stress, disease burden, and the application of the social-ecological public health model of disease prevention. In addition, it addresses therapeutic aspects, ethnic differences in traumatic stress, and future perspectives, including potential biomarkers.

Four Pistacia atlantica subspecies (atlantica, cabulica, kurdica and mutica): A review of their botany, ethnobotany, phytochemistry and pharmacology.

ETHNOPHARMACOLOGICAL RELEVANCE: Pistacia atlantica (wild pistachio) belongs to the Anacardiaceae family, and growing from the Mediterranean basin to central Asia, especially in Iran, Turkey, Iraq and Saudi Arabia where it is extensively used in traditional medicine for a wide range of ailments related to relieving upper abdominal discomfort and pain, dyspepsia and peptic ulcer. OBJECTIVE: Despite the diverse biological activities of P. atlantica, there is no current review summarizing medicinal properties of its subspecies, including cabulica, kurdica and mutica. Thus, this paper aims to explore the current understanding of the chemical, pharmacological, and biochemical properties of the extracts and the main active constituents found in each subspecies of this plant. METHODS: Peer-reviewed articles, using "Pistacia atlantica" as search term (″all fields″), were retrieved from Scifinder, Pubmed, Science direct, Wiley, Springer, ACS, Scielo, Web of Science and other web search instruments (Google Scholar, Yahoo search). Papers published until July 2020 are considered. In addition, various books were consulted that contained botanical and ethnopharmacological information. The information provided in this review is based on peer-reviewed papers in English and French. RESULTS: Phytochemical studies have shown the presence of numerous valuable compounds, including volatile compounds, flavonoids, phenolic compounds, fatty acids, tocopherols and phytosterols. P. atlantica contains also minerals and trace elements, like iron, lead, copper, potassium, sodium and calcium; fatty acids, like oleic, linoleic, and palmitic acid; fat-soluble vitamins, such as α, ß, γ and δ tocopherols; phytosterols, like betasitosterol, stigmasterol, campesterol and Δ5-avenasterol. Crude extracts and isolated compounds from P. atlantica show a wide range of pharmacological properties, such as antimicrobial, antifungal, anti-inflammatory, analgesic, antinociceptive, wound healing, anticancer, cytotoxic, anticholinesterase, antidiabetic, hepatoprotective, urease inhibition, antihypertension, nipple fissure healing, antileishmanial and antiplasmodial activities. However, there are no reports summarizing the P. atlantica bioactivity, its therapeutic value, and the roles played by each of the numerous phytoconstituents. CONCLUSION: Many traditional uses of P. atlantica and its subspecies have now been confirmed by pharmacologic research. Systematic phytochemical investigation of the P. atlantica subspecies and the pharmacological properties, especially the mechanisms of action and toxicology, to illustrate their ethnomedicinal use, to explore the therapeutic potential and support further health-care product development, will undoubtedly be the focus of further research. Therefore, detailed and extensive studies and clinical evaluation of P. atlantica subspecies should be carried out in future for the safety approval of therapeutic applications.

Defining a standardized methodology for the determination of the antioxidant capacity: case study of Pistacia atlantica leaves.

Antioxidant activity can be measured by a variety of methods, that include hydrogen atom transfer (HAT) and single electron transfer (ET) methods. Most of these techniques are spectrophotometric, and thus incapable of quantifying or indicting individual antioxidant compounds. Nowadays, the integration of chromatographic and chemometric approaches allows a high-throughput identification and activity prediction of herbal products. The ethyl acetate fraction from the aqueous-acetone extract of Pistacia atlantica leaves is frequently used for the isolation of antioxidants. In this study it is investigated for its antioxidant properties in order to define a potential methodology for the determination of the antioxidant capacity of herbal extracts (which need to be confirmed by future studies). The seven free radical assays evaluated can be divided into two groups depending on the oxidizing reagent. Three methods use stable, non-biological radicals, i.e. the diphenyl-1-picrylhydrazyl (DPPH) assay, the azinobis-(3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) assay, and the N,N-dimethyl-p-phenylenediamine (DMPD) assay, which have no direct physiological importance. Four methods work with biological radical producers, including superoxide anion (O2˙-), hydroxyl (˙OH), nitric oxide (NO˙) and peroxyl (ROO˙) are produced metabolically in living organisms, and thus direct information on an extract's protective action is obtained. Furthermore, the reducing power method by potassium ferricyanide (RPC), and the iron (ferrous) ion chelating activity also have been investigated. The antioxidant activities of the samples were measured according to the different methods and modelled as a function of the HPLC fingerprints using the partial least squares (PLS) technique. The regression coefficients of the models were studied to indicate the peaks potentially responsible for the antioxidant activity. From the combined results of the different PLS models, we recommend using the DPPH, RPC and ROO˙ assays, to evaluate the overall antioxidant capacity; in the case study of P. atlantica leaves.

Potentially antidiabetic and antihypertensive compounds identified from Pistacia atlantica leaf extracts by LC fingerprinting.

The objective of this paper is to evaluate the variations in the ability of Pistacia atlantica leaves to inhibit enzymes linked to type 2 diabetes (α-amylase and α-glucosidase) and to hypertension (angiotensin converting enzyme-I (ACE-I)), depending on harvesting month, gender and growing region, as well as to identify the peaks in chromatographic fingerprints that potentially correspond to components with enzymatic inhibitory activities. In this study, LC fingerprints of P. atlantica leave extracts were developed. Peaks which were probably responsible for the anti-amylase, anti-glucosidase and anti-ACE-I activities were assigned. For the latter purpose, the relevant information was extracted, linking the chromatographic fingerprints with the activities using a linear multivariate calibration technique, i.e., Partial Least Squares (PLS) regression. Prior to the construction of the models, the fingerprints are aligned using a warping method, called Correlation Optimized Warping (COW). Besides COW, different other data pretreatment methods were applied and compared. Our findings revealed that the influence of the growing region and gender on the α-amylase, α-glucosidase and ACE-I inhibitory activities of P. atlantica leaves was less important than the harvest time. Thirteen common peaks were selected from the chromatograms and used as a dataset to model the biological activities. The peaks potentially responsible for the biological activity of the samples were indicated by studying the regression coefficients of the models. Seven peaks corresponding to possibly anti-amylase compounds were found, while 6 peaks were considered important for inhibiting the α-glucosidase activity. Furthermore, the regression coefficients of the hypertension model indicated eight peaks as being important for inhibiting the ACE-I activity. The contributions of individual phenolic compounds of P. atlantica leaves to the α-amylase, α-glucosidase and ACE-I inhibitory activities were also identified. This investigation showed that the extract of P. atlantica leaves provides a rational basis for the isolation and development of antidiabetic and antihypertensive agents.

Seasonal, gender and regional variations in total phenolic, flavonoid, and condensed tannins contents and in antioxidant properties from Pistacia atlantica ssp. leaves.

CONTEXT: The widespread use of Pistacia atlantica Desf. ssp. (Anacardiaceae) in traditional medicine can be partly attributed to the content of its secondary metabolites, in particular, the phenolic compounds. OBJECTIVE: The effects of harvest period, growing region and gender on the phenolic compounds, flavonoids and condensed tannins contents were studied, as well as on the antioxidant activities of P. atlantica leaves in order to provide a scientific basis for optimal collection. MATERIALS AND METHODS: Leaves were collected monthly from April to October 2010 in two Algerian sites. The powdered leaves were used for preparing the ethyl acetate extract. Contents of total phenolics (TPC), flavonoids (FC) and condensed tannins (CTC) were determined spectrophotometrically. Antioxidant activity was evaluated through radical scavenging activity (RSA) of 2,2-diphenyl-1-picrylhydrazyl (250 µM) and the reducing power capacity (RPC) determination by K3Fe(CN)6 (1%). RESULTS: The TPC was found to vary from 79 ± 13 to 259 ± 8 mg gallic acid equivalents/g of dry weight (DW) during the study period. The RSA and RPC varied between 262 ± 18 and 675 ± 21 mg Ascorbic Acid Equivalent (AAE)/g DW, and from 259 ± 16 to 983 ± 20 mg AAE/g DW, respectively. A seasonal pattern was observed consisting of a decrease in TPC content and RPC from spring to autumn. The FC, CTC and RSA did not show a seasonal pattern. DISCUSSION AND CONCLUSION: Our findings showed that secondary metabolite content and antioxidant activities of P. atlantica leaves were more influenced by harvest time and growing region than by gender.

A study of in vitro antibacterial activity of lanthanides complexes with a tetradentate Schiff base ligand

Objective: To establish the antibacterial activity of lanthanides complexes with a tetradentate Schiff base ligand L. Methods: (N, N'-bis (1-naphthaldimine)-o-phenylenediamine) was prepared from the condensation of 2-hydroxy-1-naphthaldehyde with o-phenylenediamine in a molar ratio of 2:1. The antimicrobial activity of the resultant Ln (III) complexes was investigated using agar well diffusion and micro-broth dilution techniques; the latter was used to establish the minimum inhibitory concentrations for each compound investigated. Results: Most of Ln (III) complexes were found to exhibit antibacterial activities against a number of pathogenic bacteria with MICs ranging between 1.95-250.00 μg/mL. Staphylococcus aureus was the most susceptible bacterial species to [LaL(NO3)2(H2O)](NO3) complex while Shigella dysenteriae andEscherichia coli required a relatively higher MIC (250 μg/mL). The complexes La (III) and Pr (III) were effective inhibitors against Staphylococcus aureus, whereas Sm (III) complex was effective against Serratia marcescens. On the other hand, Gd (III), La (III) and Nd (III) were found to be more potent inhibitors against Pseudomonas aeruginosa than two of commonly used antibiotics. The remaining Ln (III) complexes showed no remarkable activity as compared to the two standard drugs used. Conclusions: Tetradentate Schiff base ligand L and its complexes could be a potential antibacterial compounds after further investigation.