Novel Cytotoxic Sesquiterpene Coumarin Ethers and Sulfur-Containing Compounds from the Roots of Ferula turcica.

Six new sesquiterpene coumarin ethers, namely turcicanol A (1), turcicanol A acetate (2), turcicanol B (3), turcica ketone (4), 11'-dehydrokaratavicinol (5), and galbanaldehyde (6), and one new sulfur-containing compound, namely turcicasulphide (7), along with thirty-two known secondary metabolites were isolated from the root of the endemic species Ferula turcica Akalin, Miski, & Tuncay through a bioassay-guided isolation approach. The structures of the new compounds were elucidated by spectroscopic analysis and comparison with the literature. Cell growth inhibition of colon cancer cell lines (COLO205 and HCT116) and kidney cancer cell lines (UO31 and A498) was used to guide isolation. Seventeen of the compounds showed significant activity against the cell lines.

Exploring Meditation Profiles and Predictors in Nursing Students.

Background: Nursing students face unique academic and clinical workloads linked to increased stress. Previous studies indicate formal and informal mindfulness meditation provide stress-reducing benefits. This practice aligns with holistic nursing core values of self-care and self-reflection; little is known about meditation practice in nursing students. Objectives: Our study aimed to describe meditation practice and predictors in pre-licensure nursing students. Design: Cross-sectional, multi-site. Methods: Qualtrics surveys queried individual demographics, personal meditation and exercise habits, and indicators of wellbeing. Results: Of 417 participants, 65% (n = 271) reported at least one type of meditation practice. Prayer/spiritual activities were most prevalent (almost 70%), followed by breathing exercises (41%). Meditators reported good or excellent self-rated health status or engaged in exercise (p < .05). Meditators also reported more self-compassion, happiness, and satisfaction with life, and perceived less stress than non-meditators (p < .05). Of all factors studied, only engaging in exercise significantly predicted practicing meditation (OR = 2.05, 95%CI 1.10-3.82). Conclusion: Nursing students who engage in meditation report signs of health and well-being and utilize holistic methods such as prayer and breathing. The intrinsic motivation to engage in healthy habits such as exercise may also help students engage in mindfulness meditation and is an important finding for nursing educators.

The tomato yellow leaf curl virus C4 protein alters the expression of plant developmental genes correlating to leaf upward cupping phenotype in tomato.

Tomato yellow leaf curl virus (TYLCV), a monopartite begomovirus in the family Geminiviridae, is efficiently transmitted by the whitefly, Bemisia tabaci, and causes serious economic losses to tomato crops around the world. TYLCV-infected tomato plants develop distinctive symptoms of yellowing and leaf upward cupping. In recent years, excellent progress has been made in the characterization of TYLCV C4 protein function as a pathogenicity determinant in experimental plants, including Nicotiana benthamiana and Arabidopsis thaliana. However, the molecular mechanism leading to disease symptom development in the natural host plant, tomato, has yet to be characterized. The aim of the current study was to generate transgenic tomato plants expressing the TYLCV C4 gene and evaluate differential gene expression through comparative transcriptome analysis between the transgenic C4 plants and the transgenic green fluorescent protein (Gfp) gene control plants. Transgenic tomato plants expressing TYLCV C4 developed phenotypes, including leaf upward cupping and yellowing, that are similar to the disease symptoms expressed on tomato plants infected with TYLCV. In a total of 241 differentially expressed genes identified in the transcriptome analysis, a series of plant development-related genes, including transcription factors, glutaredoxins, protein kinases, R-genes and microRNA target genes, were significantly altered. These results provide further evidence to support the important function of the C4 protein in begomovirus pathogenicity. These transgenic tomato plants could serve as basic genetic materials for further characterization of plant receptors that are interacting with the TYLCV C4.

Assessing the United States' most frequently asked questions about osteopathic medicine, osteopathic education, and osteopathic manipulative treatment.

CONTEXT: Osteopathic medicine in the United States continues to produce a substantial number of physicians and medical educators. However, recently popularized misconceptions about osteopathic medical practice, education, and manual therapy suggest an unsettling prevalence of inaccurate beliefs held by the public. The public often searches the internet to find out information about osteopathic medicine, but the content of questions and the transparency of the resulting information is unknown. OBJECTIVES: We sought to explore frequently asked questions (FAQs) generated by Google to assess commonly searched questions about the osteopathic profession and to determine the level of information transparency associated with resulting sources. METHODS: On June 16, 2021, we searched Google for three terms: "osteopathic medicine," "doctor of osteopathic medicine," and "DO," until a minimum of 100 FAQs and their answer links were extracted from each search. After excluding irrelevant FAQs, we used Rothwell's Classification of Questions to categorize the FAQs. We then used the Journal of the American Medical Association's Benchmark Criteria to assess information transparency for each corresponding answer source provided by Google. The answer sources were screened for the inappropriate use of "osteopathy" in place of "osteopathic medicine" and for "osteopath" in place of "DO," "Doctor of Osteopathic Medicine," or "Osteopathic Physician." We performed statistical tests to ascertain the differences in information transparency between osteopathic and nonosteopathic information sources. RESULTS: Our Google search revealed 110 unique FAQs about osteopathic medicine. The majority of FAQs were classified as fact-based (82/110; 74.55%), nearly half of which (45.12%) were related to the medical practicing privileges of DOs. The FAQs were most commonly answered by academic institutions (44/110, 40.0%). Nearly half (49.09%) of the linked answer sources were deemed inadequate by JAMA benchmark criteria. Of the 110 linked answer sources, 19 (17.27%) misused either osteopathy, osteopath, or both to describe osteopathic physicians. Only 30 sources were linked to US-based osteopathic organizations. Osteopathic organizations were statistically less likely to meet high-transparency criteria than nonosteopathic organizations (p=0.002). CONCLUSIONS: Our study shows that the US public may be unsure about the physician status of DOs, which may prevent securing the professional identity of osteopathic physicians in the eyes of the public. Osteopathic organizations should tailor awareness campaigns toward addressing the common misconceptions revealed by our study. Osteopathic organizations should use transparency criteria as a rubric when publishing information to enhance transparency.

Affinity Purification-Mass Spectrometry Identifies a Novel Interaction between a Polerovirus and a Conserved Innate Immunity Aphid Protein that Regulates Transmission Efficiency.

The vast majority of plant viruses are transmitted by insect vectors, with many crucial aspects of the transmission process being mediated by key protein-protein interactions. Still, very few vector proteins interacting with viruses have been identified and functionally characterized. Potato leafroll virus (PLRV) is transmitted most efficiently by Myzus persicae, the green peach aphid, in a circulative, non-propagative manner. Using affinity purification coupled to high-resolution mass spectrometry (AP-MS), we identified 11 proteins from M. persicaedisplaying a high probability of interaction with PLRV and an additional 23 vector proteins with medium confidence interaction scores. Three of these aphid proteins were confirmed to directly interact with the structural proteins of PLRV and other luteovirid species via yeast two-hybrid. Immunolocalization of one of these direct PLRV-interacting proteins, an orthologue of the human innate immunity protein complement component 1 Q subcomponent-binding protein (C1QBP), shows that MpC1QBP partially co-localizes with PLRV in cytoplasmic puncta and along the periphery of aphid gut epithelial cells. Artificial diet delivery to aphids of a chemical inhibitor of C1QBP leads to increased PLRV acquisition by aphids and subsequently increased titer in inoculated plants, supporting a role for C1QBP in the acquisition and transmission efficiency of PLRV by M. persicae. This study presents the first use of AP-MS for the in vivo isolation of a functionally relevant insect vector-virus protein complex. MS data are available from ProteomeXchange.org using the project identifier PXD022167.

Identification of potential modulators of osteosarcoma metastasis by high-throughput cellular screening of natural products.

A high-throughput screening assay was developed and applied to a large library of natural product extract samples, in order to identify compounds which preferentially inhibited the in vitro 2D growth of a highly metastatic osteosarcoma cell line (MG63.3) compared to a cognate parental cell line (MG63) with low metastatic potential. Evaluation of differentially active natural product extracts with bioassay-guided fractionation led to the identification of lovastatin (IC50  = 11 µm) and the limonoid toosendanin (IC50  = 26 nm). Other statins and limonoids were then tested, and cerivastatin was identified as a particularly potent (IC50  < 0.1 µm) and selective agent. These compounds potently and selectively induced apoptosis in MG63.3 cells, but not MG63. Assays with other cell pairs were used to examine the generality of these results. Statins and limonoids may represent unexplored opportunities for development of modulators of osteosarcoma metastasis. As cerivastatin was previously approved for clinical use, it could be considered for repurposing in osteosarcoma, pending validation in further models.

Long-Chain Omega-3 Fatty Acid Supplements in Depressed Heart Failure Patients: Results of the OCEAN Trial.

OBJECTIVES: The goal of this study was to test the effects of long-chain omega-3 fatty acid supplementation on omega-3 levels, depressive symptoms, and other psychosocial factors, as well as other chronic heart failure (CHF)-related functional measures. BACKGROUND: Patients with CHF and depression had low blood omega-3 concentrations that were associated with an elevated risk of mortality. METHODS: This study was a randomized, double-blind, placebo-controlled pilot clinical trial using a 400/200 eicosapentaenoic acid (EPA)/docosahexaenoic acid (DHA) fish oil at 2 g and an almost pure EPA at 2 g, compared with a matched placebo, daily for 12 weeks for patients with CHF and major depressive disorder. Statistical analyses included the intention-to-treat population and "completers" (defined as participants consuming ≥70% of the capsules and completing the final endpoint evaluation between 10 and 14 weeks). RESULTS: A total of 108 patients with CHF and major depressive disorder and a score ≥18 on the Hamilton Depression Scale who were randomized at 1:1:1 to the 3 interventions at 3 enrolling centers from June 12, 2014, to May 19, 2016; 80 (74.1%) qualified as completers. Intention-to-treat analyses revealed that the levels of all omega-3 variables were significantly elevated in the omega-3 groups, whereas the placebo group showed little change; there were no between-group differences with overall depression measurements. Per-protocol exploratory analyses showed that scores on the social functioning measurement of the 36-item Short Form Health Survey improved notably in the 400/200 EPA/DHA (p = 0.040) and EPA (p = 0.10) groups compared with the placebo group. Spearman correlation analysis indicated that increased omega-3 indices were associated with improved cognitive depressive symptoms. CONCLUSIONS: Omega-3 supplementation resulted in significant increases in omega-3 levels in red blood cell counts, corresponding to a particular compound of omega-3. Changes in cognitive depressive symptoms and social function were in favor of the omega-3 supplementation. Further studies with larger sample sizes are necessary to confirm the benefits of omega-3 supplementation on modifying psychosocial factors for patients with CHF. (Omega-3 Supplementation for Co-Morbid Depression and Heart Failure Treatment [OCEAN]; NCT02057406).

Traditional lecture versus jigsaw learning method for teaching Medication Therapy Management (MTM) core elements.

BACKGROUND AND PURPOSE: To determine if traditional didactic lecture or the jigsaw learning method is more effective to teach the medication therapy management (MTM) core elements in a first year pharmacy course. EDUCATIONAL ACTIVITY AND SETTING: Traditional didactic lecture and a pre-class reading assignment were used in the fall semester cohort, and the jigsaw method was used in the spring semester cohort. Jigsaw is a cooperative learning strategy requiring students to assume responsibility for learning, and subsequently teaching peers. The students were responsible for reading specific sections of the pre-class reading, and then teaching other students in small groups about their specific reading assignments. To assess potential differences, identical pre- and post-tests were administered before and after the MTM section. Additionally, grade performance on an in-class project and final exam questions were compared, and students were surveyed on perceptions of teaching method used. FINDINGS: A total of 45 and 43 students completed both the pre- and post-test in the fall and spring (96% and 93% response rate), respectively. Improvement in post-test scores favored the traditional method (p = 0.001). No statistical differences were noted between groups with grade performance on the in-class project and final exam questions. However, students favored the jigsaw method over traditional lecture and perceived improvements in problem solving skills, listening/communication skills and encouragement of cooperative learning (p = 0.018, 0.025 and 0.031). SUMMARY: Although students favored the jigsaw learning method, traditional didactic lecture was more effective for the pre- and post-knowledge test performance. This may indicate that traditional didactic lecture is more effective for more foundational content.

Guidelines for feeding very low birth weight infants.

Despite the fact that feeding a very low birth weight (VLBW) neonate is a fundamental and inevitable part of its management, this is a field which is beset with controversies. Optimal nutrition improves growth and neurological outcomes, and reduces the incidence of sepsis and possibly even retinopathy of prematurity. There is a great deal of heterogeneity of practice among neonatologists and pediatricians regarding feeding VLBW infants. A working group on feeding guidelines for VLBW infants was constituted in McMaster University, Canada. The group listed a number of important questions that had to be answered with respect to feeding VLBW infants, systematically reviewed the literature, critically appraised the level of evidence, and generated a comprehensive set of guidelines. These guidelines form the basis of this state-of-art review. The review touches upon trophic feeding, nutritional feeding, fortification, feeding in special circumstances, assessment of feed tolerance, and management of gastric residuals, gastro-esophageal reflux, and glycerin enemas.

Nothospondin, a new AP-1 inhibitory quassinoid from the Cameroonian plant Nothospondias staudtii.

A high throughput screen for inhibitors of the oncogenic transcription factor activator protein-1 (AP-1) was applied to the NCI repository of natural product extracts. The liphophilic extract of the plant Nothospondias staudtii (Simaroubaceae) displayed significant AP-1 inhibition. Bioassay-guided fractionation of the extract lead to a new quassinoid named nothospondin (1), and the known compound glaucarubinone (2). The structure of 1 was elucidated by spectroscopic methods. Compounds 1 and 2 showed potent, dose-dependent AP-1 inhibition at noncytotoxic concentrations.

An evaluation of the RNase H inhibitory effects of Vietnamese medicinal plant extracts and natural compounds.

CONTEXT: Acquired immune deficiency syndrome (AIDS) is a severe pandemic disease especially prevalent in poor and developing countries. Thus, developing specific, potent antiviral drugs that restrain infection by human immunodeficiency virus type 1 (HIV-1), a major cause of AIDS, remains an urgent priority. OBJECTIVE: This study evaluated 32 extracts and 23 compounds from Vietnamese medicinal plants for their inhibitory effects against HIV-1 ribonuclease H (RNase H) and their role in reversing the cytopathic effects of HIV. MATERIALS AND METHODS: The plants were air-dried and extracted in different solvent systems to produce plant extracts. Natural compounds were obtained as previously published. Samples were screened for RNase H inhibition followed by a cytopathic assay. Data were analyzed using the Microsoft Excel. RESULTS AND DISCUSSION: At 50 µg/mL, 11 plant extracts and five compounds inhibited over 90% of RNase H enzymatic activity. Methanol extracts from Phyllanthus reticulatus and Aglaia aphanamixis leaves inhibited RNase H activity by 99 and 98%, respectively, whereas four extracts showed modest protection against the cytopathic effects of HIV. CONCLUSION: The screening results demonstrated that the butanol (BuOH) extract of Celastrus orbiculata leaves, methanol (MeOH) extracts of Glycosmis stenocarpa stems, Eurya ciliata leaves, and especially P. reticulatus leaves showed potential RNase H inhibition and protection against the viral cytopathic effects of HIV-1. Further chemical investigations should be carried out to find the active components of these extracts and compounds as potential anti-HIV drug candidates.

Massage modalities and symptoms reported by cancer patients: narrative review.

The results of several studies on the use of massage therapies for cancer patients have been published in the peer-reviewed literature over the past 20 years. The current article provides a summary and critique of published studies in which patient-reported symptom ratings were assessed in relation to massage. Twenty-two studies are discussed. Most studies were on Swedish massage, followed by aromatherapy massage, foot reflexology, and acupressure. Symptoms assessed as outcomes included pain, fatigue, anxiety, nausea, and depression. Study designs included uncontrolled observational studies, crossover designs, and quasiexperimental and randomized controlled studies. Several studies included methodologic limitations such as small sample sizes, lack of blinded assessment, lack of accounting for subject attrition in statistical analyses, and other limitations. The results of the studies reviewed are mixed and vary as a function of several study characteristics. The most consistent symptom reduction was anxiety reduction. Additional well-designed studies are needed. Several recommendations are offered for future studies.

Synthesis of 5-deazaflavin derivatives and their activation of p53 in cells.

A family of 5-deazaflavin derivatives has been synthesised using a two-step convergent strategy. The biological activity of these compounds was evaluated in cells, by assessing their ability to stabilize and activate p53. These compounds may act as low molecular weight inhibitors of the E3 activity of HMD2 in tumours that retain wild-type p53. Importantly, we have demonstrated that the nitro group present in all three of the original lead compounds [1-3 (HL198C-E)] is not essential for observation of this biological activity.

Nutritional regulation of porcine bacterial-induced colitis by conjugated linoleic acid.

Excessive intake of saturated fatty acids and/or linoleic acid favors the induction of an array of lipid mediators and cytokines enhancing inflammatory responses. Conversely, dietary supplementation with (n-3) fatty acids or vitamin D ameliorates inflammation and autoimmune diseases. Although it was well accepted that conjugated linoleic acid (CLA) prevented diseases with a common inflammatory pathogenesis (i.e., cancer and atherosclerosis), no studies were available on the roles of CLA in mucosal inflammation. The present study was designed to investigate the anti-inflammatory actions and molecular mechanisms underlying the regulation of colonic health by CLA. We hypothesized that colonic inflammation can be ameliorated by dietary CLA supplementation. To test this hypothesis, inflammation of the colonic mucosa was triggered by challenging pigs fed either soybean oil-supplemented or CLA-supplemented diets with an enteric bacterial pathogen (i.e., Brachyspira hyodysenteriae). Immunoregulatory cytokines and peroxisome proliferator-activated receptor-gamma (PPAR-gamma) mRNA expression were assayed in colonic lymph nodes and colon of pigs. Colonic mucosal lesions and lymphocyte subset distribution were evaluated by histology and immunohistochemistry. Supplementation of CLA in the diet before the induction of colitis decreased mucosal damage; maintained cytokine profiles (i.e., interferon-gamma and interleukin-10) and lymphocyte subset distributions (i.e., CD4+ and CD8+), resembling those of noninfected pigs; enhanced colonic expression of PPAR-gamma; and attenuated growth failure. Therefore, CLA fed preventively before the onset of enteric disease attenuated inflammatory lesion development and growth failure.

High throughput screening for cyanovirin-N mimetics binding to HIV-1 gp41.

The human immunodeficiency virus type-1 (HIV-1) envelope glycoprotein gp41 is an important mediator of viral entry into host cells. Previous studies showed that the virucidal protein cyanovirin-N (CV-N) bound to both gp120 and gp41, and that this binding was associated with its antiviral activity. We constructed an HTS assay based on the interaction of europium-labeled CV-N with recombinant glycosylated gp41 ectodomain to support identification of small-molecule mimetics of CV-N that might be developed as antiviral drug leads. Primary screening of over 107,000 natural product extracts in the assay yielded 347 confirmed hits. Secondary assays eliminated extracts that bound directly to labeled CV-N or for which the simple sugars mannose and N-acetylglucosamine blocked the interaction with gp41 (lectin activity). Extracts were further prioritized based on anti-HIV activity and other biological, biochemical, and chemical criteria. The distribution of source organism taxonomy of active extracts was analyzed, as was the cross-correlation of activity between the CV-N-gp41 binding competition assay and the previously reported CV-N-gp120 binding competition assay. A limited set of extracts was selected for bioassay-guided fractionation.