Green synthesis and characterization of silver nanoparticles from Ducrosia flabellifolia Boiss. aqueous extract: Anti-quorum sensing screening and antimicrobial activities against ESKAPE pathogens.

Biosynthesis of silver nanoparticles using natural compounds derived from plant kingdom is currently used as safe and low-cost technique for nanoparticles synthesis with important abilities to inhibit multidrug resistant microorganisms (MDR). ESKAPE pathogens, especially MDR ones, are widely spread in hospital and intensive care units. In the present study, AgNPs using Ducrosia flabellifolia aqueous extract were synthesized using a reduction method. The green synthesized D. flabellifolia-AgNPs were characterized by UV-Vis spectrophotometer, Scanning electron microscopy (SEM), and X-ray diffraction assays. The tested D. flabellifolia aqueous extract was tested for its chemical composition using Liquid Chromatography-Electrospray Ionization-Mass Spectrometry (LC-ESI-MS). Anti-quorum sensing and anti-ESKAPE potential of D. flabellifolia-AgNPs was also performed.  Results from LC-ESI-MS technique revealed the identification of chlorogenic acid, protocatechuic acid, ferulic acid, caffeic acid, 2,5-dihydroxybenzoic acid, and gallic acid as main phytoconstituents. Indeed, the characterization of newly synthetized D. flabellifolia-AgNPs revealed spherical shape with mean particle size about 16.961±2.914 nm. Bio-reduction of silver was confirmed by the maximum surface plasmon resonance of D. flabellifolia-AgNPs at 430 nm. Newly synthetized D. flabellifolia-AgNPs were found to possess important anti-ESKAPE activity with low minimal inhibitory concentrations (MICs) ranging from 0.078 to 0.312 mg/mL, and low minimal bactericidal concentrations (MBCs) varying from 0.312 to 0.625 mg/mL. Moreover, D. flabellifolia-AgNPs were active against Candida utilis ATCC 9255, C. tropicalis ATCC 1362, and C. albicans ATCC 20402 with high mean diameter of growth inhibition at 5 mg/mL, low MICs, and minimal fungicidal concentrations values (MFCs). The newly synthetized D. flabellifolia-AgNPs were able to inhibit violacein production in Chromobacterium violaceum, pyocyanin in Pseudomonas aeruginosa starter strains.  Hence, the newly synthesized silver nanoparticles using D. flabellifolia aqueous extract can be used as an effective alternative to combat ESKAPE microorganisms. These silver nanoparticles can attenuate virulence of Gram-negative bacteria by interfering with the quorum sensing system and inhibiting cell-to-cell communication.

Phytochemical profiling, antioxidant, cytotoxic, and anti-inflammatory activities of Plectranthus rugosus extract and fractions: in vitro, in vivo, and in silico approaches.

BACKGROUND: Inflammation is a key biological reaction that comprises a complex network of signals that both initiate and stop the inflammation process. PURPOSE: This study targets to evaluate the anti-inflammatory potential of the leaves of the Plectranthus rugosus (P. rugosus) plant involving both in vitro and in vivo measures. The current available drugs exhibit serious side effects. Traditional medicines impart an essential role in drug development. P. rugosus is a plant used in traditional medicine of Tropical Africa, China, and Australia to treat various diseases. METHODS: Lipopolysaccharide (LPS), an endotoxin, kindles macrophages to discharge huge quantities of pro-inflammatory cytokines like TNF-α and IL-6. So, clampdown of macrophage stimulation may have a beneficial potential to treat various inflammatory disorders. The leaves of the P. rugosus are used for swelling purpose by local population; however, its use as an anti-inflammatory agent and associated disorders has no scientific evidence. RESULTS: The extracts of the plant Plectranthus rugosus ethanolic extract (PREE), Plectranthus rugosus ethyl acetate extract (PREAF), and the compound isolated (oleanolic acid) suppress the pro-inflammatory cytokines (IL-6 and TNF-α) and nitric oxide (NO), confirming its importance in traditional medicine. CONCLUSION: The pro-inflammatory cytokines are inhibited by P. rugosus extracts, as well as an isolated compound oleanolic acid without compromising cell viability.

Network Pharmacology Combined with Molecular Docking, Molecular Dynamics, and In Vitro Experimental Validation Reveals the Therapeutic Potential of Thymus vulgaris L. Essential Oil (Thyme Oil) against Human Breast Cancer.

Breast cancer is a major global health issue for women. Thyme oil, extracted from Thymus vulgaris L., has shown promising anticancer effects. In the present study, we investigated how Thyme oil can influence breast cancer treatment using a multimethod approach. We used network pharmacology to identify the active compounds of Thyme oil, their molecular targets, and the pathways involved in breast cancer. We found that Thyme oil can modulate several key proteins (EGFR, AKT1, ESR1, HSP90AA1, STAT-3, SRC, IL-6, HIF1A, JUN, and BCL2) and pathways (EGFR tyrosine kinase inhibitor resistance, prolactin signaling pathway, HIF-1 signaling pathway, estrogen signaling pathway, ERBB signaling pathway, AGE-RAGE signaling pathway, JAK-STAT signaling pathway, FoxO signaling pathway, and PI3K-AKT signaling pathway) related to breast cancer progression. We then used molecular docking and dynamics to study the interactions and stability of the Thyme oil-compound complexes. We discovered three potent compounds (aromadendrene, α-humulene, and viridiflorene) that can bind strongly to important breast cancer proteins. We also performed in vitro experiments on MCF-7 cells to confirm the cytotoxicity and antiproliferative effects of Thyme oil. We observed that Thyme oil can inhibit cancer cell growth and proliferation at a concentration of 365.37 µg/mL. Overall, our results provide a comprehensive understanding of the pharmacological mechanism of Thyme oil in breast cancer treatment and suggest its potential as a new or adjuvant therapy. Further studies are needed to validate and optimize the therapeutic efficacy of Thyme oil and its active compounds.

Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation to Elucidate the Molecular Targets and Potential Mechanism of Phoenix dactylifera (Ajwa Dates) against Candidiasis.

Candidiasis, caused by opportunistic fungal pathogens of the Candida genus, poses a significant threat to immunocompromised individuals. Natural compounds derived from medicinal plants have gained attention as potential sources of anti-fungal agents. Ajwa dates (Phoenix dactylifera L.) have been recognized for their diverse phytochemical composition and therapeutic potential. In this study, we employed a multi-faceted approach to explore the anti-candidiasis potential of Ajwa dates' phytochemicals. Utilizing network pharmacology, we constructed an interaction network to elucidate the intricate relationships between Ajwa dates phytoconstituents and the Candida-associated molecular targets of humans. Our analysis revealed key nodes in the network (STAT3, IL-2, PTPRC, STAT1, CASP1, ALB, TP53, TLR4, TNF and PPARG), suggesting the potential modulation of several crucial processes (the regulation of the response to a cytokine stimulus, regulation of the inflammatory response, positive regulation of cytokine production, cellular response to external stimulus, etc.) and fungal pathways (Th17 cell differentiation, the Toll-like receptor signaling pathway, the C-type lectin receptor signaling pathway and necroptosis). To validate these findings, molecular docking studies were conducted, revealing the binding affinities of the phytochemicals towards selected Candida protein targets of humans (ALB-rutin (-9.7 kJ/mol), STAT1-rutin (-9.2 kJ/mol), STAT3-isoquercetin (-8.7 kJ/mol), IL2-ß-carotene (-8.5 kJ/mol), CASP1-ß-carotene (-8.2 kJ/mol), TP53-isoquercetin (-8.8 kJ/mol), PPARG-luteolin (-8.3 kJ/mol), TNF-ßcarotene (-7.7 kJ/mol), TLR4-rutin (-7.4 kJ/mol) and PTPRC-rutin (-7.0 kJ/mol)). Furthermore, molecular dynamics simulations of rutin-ALB and rutin-STAT1 complex were performed to gain insights into the stability and dynamics of the identified ligand-target complexes over time. Overall, the results not only contribute to the understanding of the molecular interactions underlying the anti-fungal potential of specific phytochemicals of Ajwa dates in humans but also provide a rational basis for the development of novel therapeutic strategies against candidiasis in humans. This study underscores the significance of network pharmacology, molecular docking and dynamics simulations in accelerating the discovery of natural products as effective anti-fungal agents. However, further experimental validation of the identified compounds is warranted to translate these findings into practical therapeutic applications.

Clinical remission in severe asthma with biologic therapy: an analysis from the UK Severe Asthma Registry.

BACKGROUND: Novel biologic therapies have revolutionised the management of severe asthma with more ambitious treatment aims. Here we analyse the definition of clinical remission as a suggested treatment goal and consider the characteristics associated with clinical remission in a large, real-world severe asthma cohort. METHODS: This was a retrospective analysis of severe asthma patients registered in the UK Severe Asthma Registry (UKSAR) who met strict national access criteria for biologics. Patients had a pre-biologics baseline assessment and annual review. The primary definition of clinical remission applied included Asthma Control Questionnaire (ACQ)-5 <1.5 and no oral corticosteroids for disease control and forced expiratory volume in 1 s above lower limit of normal or no more than 100 mL less than baseline. RESULTS: 18.3% of patients achieved the primary definition of remission. The adjusted odds of remission on biologic therapy were 7.44 (95% CI 1.73-31.95)-fold higher in patients with type 2 (T2)-high biomarkers. The adjusted odds of remission were lower in patients who were female (OR 0.61, 95% CI 0.45-0.93), obese (OR 0.49, 95% CI 0.24-0.65) or had ACQ-5 ≥1.5 (OR 0.19, 95% CI 0.12-0.31) pre-biologic therapy. The likelihood of remission reduced by 14% (95% CI 0.76-0.97) for every 10-year increase in disease duration. 12-21% of the cohort attained clinical remission depending on the definition applied; most of those who did not achieve remission failed to meet multiple criteria. CONCLUSIONS: 18.3% of patients achieved the primary definition of clinical remission. Remission was more likely in T2-high biomarker patients with shorter duration of disease and less comorbidity. Further research on the optimum time to commence biologics in severe asthma is required.

In Vitro Antiproliferative Apoptosis Induction and Cell Cycle Arrest Potential of Saudi Sidr Honey against Colorectal Cancer.

A range of natural products have been extensively studied for their chemopreventive potential for cancer, including those that inhibit growth and induce apoptosis. Sidr honey derived from the Ziziphus or Lote tree (Ziziphus spina-christi, Ziziphus lotus, or Ziziphus jujuba) is used in a wide range of traditional medicine practices. In the current study, the Saudi Sidr honey was analyzed by means of a GC-MS chromatogram and investigated for its antiproliferative effects on colorectal cancer cells (HCT-116), breast cancer cells (MCF-7), and lung cancer cells (A-549), as well as its apoptosis induction and cell cycle arrest potentials against human colorectal cancer cells (HCT-116). The effects of Saudi Sidr honey on cells were determined using the MTT assay and the clonogenic assay. The induction of apoptosis was studied using Annexin V-FITC flow cytometry analysis. The propidium iodide staining method was used to detect cell cycle arrest via flow cytometry. By means of performing GS-MS and HR-LCMS analysis, 23 different chemical components were identified from Saudi Sidr honey. A dose-response analysis showed that Saudi Sidr honey was more effective against HCT-116 (IC50 = 61.89 ± 1.89 µg/mL) than against MCF-7 (IC50 = 78.79 ± 1.37 µg/mL) and A-549 (IC50 = 94.99 ± 1.44 µg/mL). The antiproliferation activity of Saudi Sidr honey has been found to be linked to the aggregation of cells during the G1 phase, an increase in early and late apoptosis, and necrotic cell death in HCT-116 cells. Considering these promising findings that highlight the potential use of Saudi Sidr honey as an antitumor agent, further research should be carried out with the aim of isolating, characterizing, and evaluating the bioactive compounds involved in Sidr honey's antiproliferative activity to better understand the mechanism of their action.

Synergistic Antimicrobial Activity of Ceftriaxone and Polyalthia longifolia Methanol (MEPL) Leaf Extract against Methicillin-Resistant Staphylococcus aureus and Modulation of mecA Gene Presence.

Medicinal plants are an essential source of traditional curatives for numerous skin diseases. Polyalthia longifolia (Sonn.) Thwaites (Annonaceae family) is a medicinal plant used to cure skin illnesses. P. longifolia is usually applied in folkloric therapeutical systems to treat skin diseases. The methicillin-resistant Staphylococcus aureus (MRSA) bacteria is among the essential bacteria contributing to skin diseases. Hence, to verify the traditional medicinal claim of P. longifolia usage in skin disease treatment, the current research was performed to study the synergistic antibacterial activity of standardized Polyalthia longifolia methanol leaf extract (MEPL) against MRSA bacteria. The synergistic antimicrobial activity result of ceftriaxone, when mixed with MEPL, against MRSA was investigated by the disc diffusion method, broth microdilution method, checkerboard dilution test, and modulation of mecA gene expression by multiplex polymerase chain reaction (multiplex PCR). The MEPL extract exhibited good synergistic antimicrobial activity against MRSA. Using the checkerboard method, we confirmed the synergistic effect of MEPL from P. longifolia and ceftriaxone (2:1) for MRSA with a marked reduction of the MIC value of the ceftriaxone from 8000 µg/mL to 1000 µg/mL. Moreover, the combination of MEPL with ceftriaxone significantly (p < 0.05) inhibited the presence of the resistant mecA gene in the tested strain. The LC-ESI-MS/MS analysis identified compounds that were reported to exhibit antimicrobial activity. Conclusively, the MEPL extract, an important etiological agent for skin diseases, showed worthy synergistic antimicrobial action against MRSA bacteria, thus supporting the traditional use of P. longifolia.

Integrating network pharmacology approaches for the investigation of multi-target pharmacological mechanism of 6-shogaol against cervical cancer.

Traditional treatment of cancer has been plagued by a number of obstacles, such as multiple drug resistance, toxicity and financial constraints. In contrast, phytochemicals that modulate a variety of molecular mechanisms are garnering increasing interest in complementary and alternative medicine. Therefore, an approach based on network pharmacology was used in the present study to explore possible regulatory mechanisms of 6-shogaol as a potential treatment for cervical cancer (CC). A number of public databases were screened to collect information on the target genes of 6-shogaol (SuperPred, Targetnet, Swiss target prediction and PharmMapper), while targets pertaining to CC were taken from disease databases (DisGeNet and Genecards) and gene expression omnibus (GEO) provided expression datasets. With STRING and Cytoscape, protein-protein interactions (PPI) were generated and topology analysis along with CytoNCA were used to identify the Hub genes. The Gene Ontology (GO) database Enrichr was used to annotate the target proteins, while, using the Kyoto Encyclopedia of Genes and Genomes (KEGG) database, signaling pathway enrichment analysis was conducted. Molecular docking and survival analysis for the Hub genes revealed four genes (HSP90AA1, HRAS, ESR1 and EGFR) with lowest binding energy and majority of the Hub genes (EGFR, SRC, CASP-3, HSP90AA1, MTOR, MAPK-1, MDM2 and ESR1) were linked with the overall survival of CC patients. In conclusion, the present study provides the scientific evidence which strongly supports the use of 6-shogoal as an inhibitor of cellular proliferation, growth, migration as well as inducer of apoptosis via targeting the hub genes involved in the growth of CC.Communicated by Ramaswamy H. Sarma.

Structure-Guided Approach to Discover Tuberosin as a Potent Activator of Pyruvate Kinase M2, Targeting Cancer Therapy.

Metabolic reprogramming is a key attribute of cancer progression. An altered expression of pyruvate kinase M2 (PKM2), a phosphotyrosine-binding protein is observed in many human cancers. PKM2 plays a vital role in metabolic reprogramming, transcription and cell cycle progression and thus is deliberated as an attractive target in anticancer drug development. The expression of PKM2 is essential for aerobic glycolysis and cell proliferation, especially in cancer cells, facilitating selective targeting of PKM2 in cell metabolism for cancer therapeutics. We have screened a virtual library of phytochemicals from the IMPPAT (Indian Medicinal Plants, Phytochemistry and Therapeutics) database of Indian medicinal plants to identify potential activators of PKM2. The initial screening was carried out for the physicochemical properties of the compounds, and then structure-based molecular docking was performed to select compounds based on their binding affinity towards PKM2. Subsequently, the ADMET (absorption, distribution, metabolism, excretion and toxicity) properties, PAINS (Pan-assay interference compounds) patterns, and PASS evaluation were carried out to find more potent hits against PKM2. Here, Tuberosin was identified from the screening process bearing appreciable binding affinity toward the PKM2-binding pocket and showed a worthy set of drug-like properties. Finally, molecular dynamics simulation for 100 ns was performed, which showed decent stability of the protein-ligand complex and relatival conformational dynamics throughout the trajectory. The study suggests that modulating PKM2 with natural compounds is an attractive approach in treating human malignancy after required validation.

Chemical Composition and the Anticancer, Antimicrobial, and Antioxidant Properties of Acacia Honey from the Hail Region: The in vitro and in silico Investigation.

In consideration of the emergence of novel drug-resistant microbial strains and the increase in the incidences of various cancers throughout the world, honey could be utilized as a great alternative source of potent bioactive compounds. In this context, this study pioneers in reporting the phytochemical profiling and the antimicrobial, antioxidant, and anticancer properties of Acacia honey (AH) from the Hail region of Saudi Arabia, assessed using in vitro and molecular docking approaches. The phytochemical profiling based on high-resolution liquid chromatography-mass spectrometry (HR-LCMS) revealed eight compounds and three small peptide-like proteins as the constituents. The honey samples exhibited promising antioxidant activities (DPPH-IC50 = 0.670 mg/mL; ABTS-IC50 = 1.056 mg/mL; ß-carotene-IC50 > 5 mg/mL). In the well-diffusion assay, a high mean growth inhibition zone (mGIZ) was observed against Staphylococcus aureus (48.33 ± 1.53 mm), Escherichia coli ATCC 10536 (38.33 ± 1.53 mm), and Staphylococcus epidermidis ATCC 12228 (39.33 ± 1.15 mm). The microdilution assay revealed that low concentrations of AH could inhibit the growth of almost all the evaluated bacterial and fungal strains, with the minimal bactericidal concentration values (MBCs) ranging from 75 mg/mL to 300 mg/mL. On the contrary, high AH concentrations were required to kill the tested microorganisms, with the minimal bactericidal concentration values (MBCs) ranging from approximately 300 mg/mL to over 600 mg/mL and the minimal fungicidal concentration values (MFCs) of approximately 600 mg/mL. The AH exhibited effective anticancer activity in a dose-dependent manner against breast (MCF-7), colon (HCT-116), and lung (A549) cancer cell lines, with the corresponding IC50 values of 5.053 µg/mL, 5.382 µg/mL, and 6.728 µg/mL, respectively. The in silico investigation revealed that the observed antimicrobial, antioxidant, and anticancer activities of the constituent compounds of AH are thermodynamically feasible, particularly those of the tripeptides (Asp-Trp-His and Trp-Arg-Ala) and aminocyclitol glycoside. The overall results highlighted the potential of AH as a source of bioactive compounds with significant antimicrobial, antioxidant, and anticancer activities, which could imply further pharmacological applications of AH.

Cytotoxic Activity, Cell Cycle Inhibition, and Apoptosis-Inducing Potential of Athyrium hohenackerianum (Lady Fern) with Its Phytochemical Profiling.

In the present study, we investigated the cytotoxic effects of Athyrium hohenackerianum ethanolic extract (AHEE) on the proliferation of breast, lung, and colon cancer cells. The AHEE was tested for its effect on the progression of the cell cycle, followed by induction of apoptosis determination by flow cytometry. Real-time qRT-PCR was also utilized to observe the initiation of apoptosis. In addition, GC-MS was performed in order to identify the active phytochemicals present in the AHEE. A cytotoxic activity with an IC50 value of 123.90 µg/mL against HCT-116 colon cancer cells was exhibited by AHEE. Following propidium iodide staining, annexin-V/PI, and clonogenic assays, AHEE treatment results in cell arrest in the S phase, causing an increase in the early and late phases of apoptosis and displaying antiproliferative potential, respectively. The morphological alterations were further monitored using acridine orange/ethidium bromide (AO/EB) staining. When compared with the control cells, features of apoptotic cell death, including nuclear fragmentation, in the AHEE-treated cells were noticed. The apoptosis was also confirmed by detecting the increased expression of p53 and caspase-3 along with the downregulation of Bcl-2. GC-MS analysis revealed that trans-linalool oxide, loliolide, phytol, 4,8,12,16-tetramethylheptadecan-4-olide, and gamma-sitosterol were the major phytochemical constituents. Based on these findings, it can be suggested that AHEE causes cellular death via apoptosis, which should be further explored for the identification of active compounds responsible for these observed effects. Therefore, AHEE can be used in the pharmaceutical development of anticancer agents for cancer therapeutics.

Phytochemical Analysis, Antioxidant, Antimicrobial, and Anti-Swarming Properties of Hibiscus sabdariffa L. Calyx Extracts: In Vitro and In Silico Modelling Approaches.

The aim of this study was to investigate the phytochemical composition of dried Roselle calyx (Hibiscus sabdariffa L.) using both ethanolic and aqueous extracts. We report the antimicrobial activities against a wide range of bacteria, yeast, and fungi. The antioxidant activities were tested using 2,2-diphenyl-1-picrylhydrazyl (DPPH), hydroxyl, and 2-2'-azinobis-(3-ethylbenzthiazoline-6-sulfonic acid) radical scavenging assays. We report also for the first time the effect of the swarming motility in Pseudomonas aeruginosa PAO1. Our results showed that the tested two extracts were a rich source of phenols, flavonoids, and tannins with different degrees. Additionally, eleven phytoconstituents were identified by LC/MS technique (Hibiscus acid: 3-caffeoylquinic acid, 5-caffeoylquinic acid, 5-feruloylquinic acid, cyanidin 3-o-glucoside, myricetin, quercetin 7-o-rutinoside, quercetin 3-o-glucoside, delphinidin 3-o-sambubioside, and kaempferol 3-o-p-coumaroyl-glucoside). Also, it was shown that the calyx extract can scavenge 86% of the DPPH radical, while the rate of 53% and 23% of inhibition of the DPPH was obtained only at the concentration of 125 and 50 µg/mL, and a small inhibition was made at a concentration of 5 µg/mL. Roselle extracts inhibited the growth of the selected microorganisms at low concentrations, while higher concentrations are needed to completely kill them. However, no activity against CVB-3 was recorded for both extracts. In addition, the obtained extracts reduced the swarming motility of P. aeruginosa at 2.5 mg/ml. The docking simulation showed acceptable binding affinities (up to -9.6 kcal/mol) and interaction with key residues of 1JIJ, 2QZW, and 2UVO. The obtained results highlighted the potential use of Roselle extract as a source of phytoconstituents with promising antimicrobial, antioxidant, and anti-quorum sensing activities.

Phytochemical and In Silico ADME/Tox Analysis of Eruca sativa Extract with Antioxidant, Antibacterial and Anticancer Potential against Caco-2 and HCT-116 Colorectal Carcinoma Cell Lines.

Eruca sativa Mill. (E. sativa) leaves recently grabbed the attention of scientific communities around the world due to its potent bioactivity. Therefore, the present study investigates the metabolite profiling of the ethanolic crude extract of E. sativa leaves using high resolution-liquid chromatography-mass spectrometry (HR-LC/MS), including antibacterial, antioxidant and anticancer potential against human colorectal carcinoma cell lines. In addition, computer-aided analysis was performed for determining the pharmacokinetic properties and toxicity prediction of the identified compounds. Our results show that E. sativa contains several bioactive compounds, such as vitamins, fatty acids, alkaloids, flavonoids, terpenoids and phenols. Furthermore, the antibacterial assay of E. sativa extract showed inhibitory effects of the tested pathogenic bacterial strains. Moreover, the antioxidant activity of 2,2-diphenyl-1-picrylhydrazyl (DPPH) and hydrogen peroxide (H2O2) were found to be IC50 = 66.16 µg/mL and 76.05 µg/mL, respectively. E. sativa also showed promising anticancer activity against both the colorectal cancer cells HCT-116 (IC50 = 64.91 µg/mL) and Caco-2 (IC50 = 83.98 µg/mL) in a dose/time dependent manner. The phytoconstituents identified showed promising pharmacokinetics properties, representing a valuable source for drug or nutraceutical development. These investigations will lead to the further exploration as well as development of E. sativa-based nutraceutical products.

Chemical Composition of Ducrosia flabellifolia L. Methanolic Extract and Volatile Oil: ADME Properties, In Vitro and In Silico Screening of Antimicrobial, Antioxidant and Anticancer Activities.

In the present study, the chemical composition of the volatile oil and methanolic extract from Ducrosia flabellifolia Boiss. was investigated. The antimicrobial, antioxidant, and anticancer activities of the methanolic extract from D. flabellifolia aerial parts were screened using experimental and computational approaches. Results have reported the identification of decanal (28.31%) and dodecanal (16.93%) as major compounds in the essential oil obtained through hydrodistillation. Farnesyl pyrophosphate, Methyl 7-desoxypurpurogallin-7-carboxylate trimethyl ether, Dihydro-Obliquin, Gummiferol, 2-Phenylaminoadenosine, and 2,4,6,8,10-dodecapentaenal, on the other hand, were the dominant compounds in the methanolic extract. Moreover, the tested extract was active against a large collection of bacteria and yeast strains with diameter of growth inhibition ranging from 6.67 ± 0.57 mm to 17.00 ± 1.73 mm, with bacteriostatic and fungicidal activities against almost all tested microorganisms. In addition, D. flabellifolia methanolic extract was dominated by phenolic compounds (33.85 ± 1.63 mg of gallic acid equivalent per gram of extract) and was able to trap DPPH• and ABTS•+ radicals with IC50 about 0.05 ± 0 mg/mL and 0.105 ± 0 mg/mL, respectively. The highest percentages of anticancer activity were recorded at 500 µg/mL for all cancer cell lines with IC50 about 240. 56 µg/mL (A-549), 202.94 µg/mL (HCT-116), and 154.44 µg/mL (MCF-7). The in-silico approach showed that D. flabellifolia identified compounds bound 1HD2, 2XCT, 2QZW, and 3LN1 with high affinities, which together with molecular interactions and the bond network satisfactorily explain the experimental results using antimicrobial, antioxidant, and anticancer assays. The obtained results highlighted the ethnopharmacological properties of the rare desertic D. flabellifolia plant species growing wild in Hail region (Saudi Arabia).

Effect of Goal-Setting Approaches Within a Gamification Intervention to Increase Physical Activity Among Economically Disadvantaged Adults at Elevated Risk for Major Adverse Cardiovascular Events: The ENGAGE Randomized Clinical Trial.

Importance: Health promotion efforts commonly communicate goals for healthy behavior, but the best way to design goal setting among high-risk patients has not been well examined. Objective: To test the effectiveness of different ways to set and implement goals within a behaviorally designed gamification intervention to increase physical activity. Design, Setting, and Participants: Evaluation of the Novel Use of Gamification With Alternative Goal-setting Experiences was conducted from January 15, 2019, to June 1, 2020. The 24-week randomized clinical trial included a remotely monitored 8-week introductory intervention period, 8-week maintenance intervention period, and 8-week follow-up period. A total of 500 adults from lower-income neighborhoods in and around Philadelphia, Pennsylvania, who had either an atherosclerotic cardiovascular disease (ASCVD) condition or a 10-year ASCVD risk score greater than or equal to 7.5% were enrolled. Participants were paid for enrolling in and completing the trial. Interventions: All participants used a wearable device to track daily steps, established a baseline level, and were then randomly assigned to an attention control or 1 of 4 gamification interventions that varied only on how daily step goals were set (self-chosen or assigned) and implemented (immediately or gradually). Main Outcome Measures: The primary outcome was change in mean daily steps from baseline to the 8-week maintenance intervention period. Other outcomes included changes in minutes of moderate to vigorous physical activity. All randomly assigned participants were included in the intention-to-treat analysis. Results: Of the 500 participants, 331 individuals (66.2%) were Black, 114 were White (22.8%), and 348 were women (69.6%). Mean (SD) age was 58.5 (10.8) years and body mass index was 33.2 (7.8). A total of 215 participants (43.0%) had an ASCVD condition. Compared with the control arm, participants with self-chosen and immediate goals had significant increases in the number of daily steps during the maintenance intervention period (1384; 95% CI, 805-1963; P < .001) that were sustained during the 8-week follow-up (1391; 95% CI, 785-1998; P < .001). This group also had significant increases in daily minutes of moderate to vigorous physical activity during the maintenance intervention (4.1; 95% CI, 1.8-6.4; P < .001) that were sustained during follow-up (3.5; 95% CI, 1.1-5.8; P = .004). No other gamification arms had consistent increases in physical activity compared with the control arm. No major adverse events were reported. Conclusions and Relevance: In this trial among economically disadvantaged adults at elevated risk for major adverse cardiovascular events, a gamification intervention led to increases in physical activity that were sustained during 8 weeks of follow-up when goals were self-chosen and implemented immediately. Trial Registration: ClinicalTrials.gov Identifier: NCT03749473.

Phytochemistry, Bioactivities, Pharmacokinetics and Toxicity Prediction of Selaginella repanda with Its Anticancer Potential against Human Lung, Breast and Colorectal Carcinoma Cell Lines.

In this study, we investigated the bioactive potential (antibacterial and antioxidant), anticancer activity and detailed phytochemical analysis of Selaginellarepanda (S. repanda) ethanolic crude extract for the very first time using different in vitro approaches. Furthermore, computer-aided prediction of pharmacokinetic properties and safety profile of the identified phytoconstituents were also employed in order to provide some useful insights for drug discovery. S. repanda, which is a rich source of potent natural bioactive compounds, showed promising antibacterial activity against the tested pathogenic bacteria (S. aureus, P. aeruginosa, E. coli and S. flexneri). The crude extract displayed favorable antioxidant activity against both 2,2-diphenyl-1-picrylhydrazyl (DPPH) (IC50 = 231.6 µg/mL) and H2O2 (IC50 = 288.3 µg/mL) molecules. S. repanda also showed favorable and effective anticancer activity against all three malignant cancer cells in a dose/time dependent manner. Higher activity was found against lung (A549) (IC50 = 341.1 µg/mL), followed by colon (HCT-116) (IC50 = 378.8 µg/mL) and breast (MCF-7) (IC50 = 428.3 µg/mL) cancer cells. High resolution-liquid chromatography-mass spectrometry (HR-LC-MS) data of S. repanda crude extract revealed the presence of diverse bioactive/chemical components, including fatty acids, alcohol, sugar, flavonoids, alkaloids, terpenoids, coumarins and phenolics, which can be the basis and major cause for its bioactive potential. Therefore, achieved results from this study confirmed the efficacy of S. repanda and a prospective source of naturally active biomolecules with antibacterial, antioxidant and anticancer potential. These phytocompounds alone with their favorable pharmacokinetics profile suggests good lead and efficiency of S. repanda with no toxicity risks. Finally, further in vivo experimental investigations can be promoted as probable candidates for various therapeutic functions, drug discovery and development.

Plants-Derived Biomolecules as Potent Antiviral Phytomedicines: New Insights on Ethnobotanical Evidences against Coronaviruses.

SARS-CoV-2 infection (COVID-19) is in focus over all known human diseases, because it is destroying the world economy and social life, with increased mortality rate each day. To date, there is no specific medicine or vaccine available against this pandemic disease. However, the presence of medicinal plants and their bioactive molecules with antiviral properties might also be a successful strategy in order to develop therapeutic agents against SARS-CoV-2 infection. Thus, this review will summarize the available literature and other information/data sources related to antiviral medicinal plants, with possible ethnobotanical evidence in correlation with coronaviruses. The identification of novel antiviral compounds is of critical significance, and medicinal plant based natural compounds are a good source for such discoveries. In depth search and analysis revealed several medicinal plants with excellent efficacy against SARS-CoV-1 and MERS-CoV, which are well-known to act on ACE-2 receptor, 3CLpro and other viral protein targets. In this review, we have consolidated the data of several medicinal plants and their natural bioactive metabolites, which have promising antiviral activities against coronaviruses with detailed modes of action/mechanism. It is concluded that this review will be useful for researchers worldwide and highly recommended for the development of naturally safe and effective therapeutic drugs/agents against SARS-CoV-2 infection, which might be used in therapeutic protocols alone or in combination with chemically synthetized drugs.

Improving bioremediation process of petroleum wastewater using biosurfactants producing Stenotrophomonas sp. S1VKR-26 and assessment of phytotoxicity.

Primarily, this study aims to evaluate the biosurfactant production capability of Stenotrophomonas sp. S1VKR-26, profiling of its bioremediation ability to remediate petroleum refinery wastewater in a lab-scale bioreactor and assessment of phytotoxicity of bioremediated petroleum wastewater. As a result, strain S1VKR-26 was found to produce 5.15 g L-1 biosurfactant, CMC of 30 mg L-1 and reduced the surface tension from 60.3 to 30.5 mN m-1. Different PAHs like naphthalene (93%), phenanthrene (86%), fluoranthene (92%), and pyrene (98.3%), total petroleum hydrocarbons (72.33%) and phenolic compounds (93.06%) were significantly remediated from the wastewater after the treatment of strain S1VKR-26. Moreover, S1VKR-26 strain treated 1:1 diluted petroleum wastewater have higher germination (100%), vigor (486), and seedling (4.86 cm) compared to untreated wastewater. Therefore, the treatment of petroleum refinery wastewater with strain S1VKR-26 could be more effective in the sense of environmental safety and irrigation for crop production in agriculture.

Cordycepin for Health and Wellbeing: A Potent Bioactive Metabolite of an Entomopathogenic Cordyceps Medicinal Fungus and Its Nutraceutical and Therapeutic Potential.

Cordyceps is a rare naturally occurring entomopathogenic fungus usually found at high altitudes on the Himalayan plateau and a well-known medicinal mushroom in traditional Chinese medicine. Cordyceps contains various bioactive components, out of which, cordycepin is considered most vital, due to its utmost therapeutic as well as nutraceutical potential. Moreover, the structure similarity of cordycepin with adenosine makes it an important bioactive component, with difference of only hydroxyl group, lacking in the 3' position of its ribose moiety. Cordycepin is known for various nutraceutical and therapeutic potential, such as anti-diabetic, anti-hyperlipidemia, anti-fungal, anti-inflammatory, immunomodulatory, antioxidant, anti-aging, anticancer, antiviral, hepato-protective, hypo-sexuality, cardiovascular diseases, antimalarial, anti-osteoporotic, anti-arthritic, cosmeceutical etc. which makes it a most valuable medicinal mushroom for helping in maintaining good health. In this review, effort has been made to bring altogether the possible wide range of cordycepin's nutraceutical potential along with its pharmacological actions and possible mechanism. Additionally, it also summarizes the details of cordycepin based nutraceuticals predominantly available in the market with expected global value. Moreover, this review will attract the attention of food scientists, nutritionists, pharmaceutical and food industries to improve the use of bioactive molecule cordycepin for nutraceutical purposes with commercialization to aid and promote healthy lifestyle, wellness and wellbeing.