Authors: Sarani Kankanamge , Zeinab G. Khalil , Thulasi Sritharan , Robert J. Capon

In Other, Nature

By NCBI Pubmed

Fungal indole diterpenes (IDTs) occupy a valuable region of bioactive natural product chemical space, displaying potent and selective inhibition of therapeutically important ion channels and with potential application in the treatment of glaucoma, cancer, and neurodegenerative diseases, as well as insecticides and antivirals. We have employed an integrated workflow of analytical scale chemical profiling using GNPS (Global Natural Products Social molecular networking) and cultivation profiling (also known as “MATRIX” miniaturized microbioreactor) to detect, prioritize, optimize the production, isolate, characterize, and identify a new series of indole diterpenes, noonindoles G–L (7–12), from an Australian marine-derived fungus, Aspergillus noonimiae CMB-M0339. The first reported examples of IDT glycosides, the molecular structures for 7–12, were assigned on the basis of detailed spectroscopic analysis and biosynthetic considerations.

Authors: Carmen Monthé-Drèze , Izzuddin M. Aris , Sheryl L. Rifas-Shiman

In Public Health

By NCBI Pubmed

Importance: Prenatal psychosocial stress and nutrition may each program offspring adiposity, an important predictor of lifelong cardiometabolic health. Although increased stress and poor nutrition have been found to co-occur in pregnancy, little is known about their combined longitudinal associations in the offspring. Objective: To investigate whether the associations of the Dietary Inflammatory Index (DII) with offspring adiposity differ by prenatal stress levels and whether these associations change with age. Design, setting, and participants: Project Viva, a prospective prebirth cohort study of mother-child dyads in Massachusetts, included singleton children of mothers enrolled between April 1999 and July 2002, with follow-up visits at early childhood, midchildhood, and early adolescence. Data analysis was performed from October 31, 2020, to October 31, 2022. Exposures: Food frequency-derived DII score in pregnancy was the exposure. Effect modifiers included stress-related measures in pregnancy; depressive symptoms assessed using the Edinburgh Postnatal Depression Scale (EPDS), dichotomized at scores greater than or equal to 13 vs less than 13; and census tract-level social vulnerability (overall Social Vulnerability Index and its 4 main subindices), dichotomized at the 75th percentile. Main outcomes and measures: Overall adiposity, comprising sex- and age-standardized body mass index (BMI z), sum of subscapular and triceps skinfolds, fat mass index (FMI), and body fat percentage estimated using bioelectrical impedance analysis (BIA) and dual x-ray absorptiometry (DXA); and central adiposity, comprising waist circumference, ratio of subscapular to triceps skinfolds, and DXA-derived trunk FMI. Results: Among 1060 mother-child dyads, mean (SD) maternal age was 32.6 (4.6) years, and 811 (77%) mothers were non-Hispanic White. Mean (SD) DII score was -2.7 (1.3) units, Social Vulnerability Index level was 38th (27th) percentile, and 8% of mothers had depressive symptoms. Mean (SD) age of the children was 3.3 (0.3) years at the early childhood visit, 7.9 (0.8) years at the midchildhood visit, and 13.2 (0.9) years at the early adolescence visit. In adjusted analyses, children born to mothers in the highest (vs lowest) quartile of DII had slower decrease in BMI z scores (β, 0.03 SD units/y; 95% CI, 0.01-0.05 SD units/y), and faster adiposity gain (eg, BIA total FMI β, 0.11 kg/m2/y; 95% CI, 0.03-0.19 kg/m2/y) over time. Associations of prenatal DII quartiles with childhood adiposity were stronger (eg, BIA total FMI quartile 4 vs quartile 1 change in β, 1.40 kg/m2; 95% CI, 0.21-2.59 kg/m2) among children of mothers with high vs low EPDS scores in pregnancy, although EPDS scores did not modify the change over time. Associations of prenatal DII with adiposity change over time, however, were greater among children whose mothers lived in neighborhoods with a high (BIA percentage body fat: β, 0.55% per year; 95% CI, 0.04%-1.07% per year) vs low (β, 0.13% per year; 95% CI, -0.20 to 0.46% per year), percentage of racial and ethnic minorities, and residents with limited English-language proficiency. Conclusions and relevance: The findings of this cohort study suggest that it may be useful to simultaneously evaluate prenatal diet and psychosocial stress in women as targets for interventions intended to prevent excess childhood adiposity.

Authors: Michael Böhm , Jan-Christian Reil , Prakash Deedwania , Jae B. Kim , Jeffrey S. Borer

In Medicine and Health Sciences, Medicine, Public Health

By NCBI Pubmed

Resting heart rate is central to cardiac output and is influenced by changes occurring in numerous diseases. It predicts longevity and cardiovascular diseases, and current evidence suggests that it is also an important marker of outcome in cardiovascular disease, including heart failure. Beta-blockers improve outcomes in heart failure; however, they have effects outside reducing heart rate. Ivabradine has demonstrated efficacy in reducing rehospitalizations and mortality in heart failure and in improving exercise tolerance and reducing angina attacks in patients with coronary artery disease, whereas selective heart rate reduction may also prove to be beneficial in therapeutic areas outside those in which ivabradine has already demonstrated clinical efficacy. This review provides an update on the associations between heart rate and cardiovascular outcomes in various conditions, the experimental effects of heart rate reduction with ivabradine, and the potential new indications in cardiovascular disease.

Authors: Gary D. James , Linda M. Gerber

In Life Sciences, Biology

By NCBI Pubmed

Human biologists have been examining arterial blood pressure since they began studying the effects of the environment and culture on the health of diverse populations. The Korotkoff auscultatory technique with a trained observer and aneroid sphygmomanometer is the method of choice for blood pressure measurement in many bioanthropological field contexts. Korotkoff sounds (the first and fifth phases) are the preferred determinants of systolic and diastolic pressure, even in infants, children, pregnant women, and the elderly. Training of observers, positioning of individuals, and selection of cuff size are all essential for obtaining standardized measurements. Automatic electronic devices are increasingly being used for blood pressure measurement in human biological studies. The automatic monitors often use the oscillometric method for measuring pressure, but must be validated before use. The emergence of automatic ambulatory blood pressure monitors has opened another avenue of research on blood pressure in human biology, where allostasis and circadian responses to environmental change and real life behavioral challenges can be defined and evaluated, largely because there is now the ability to make multiple measurements over time and in varying contexts. Stand-alone automatic monitors can also be substituted for manual auscultated readings in field contexts, although in studies where participants measure their own pressure, education about how the devices work and protocol specifics are necessary. Finally, computer-driven plethysmographic devices that measure pressure in the finger are available to evaluate short-term reactivity to specific challenges.

Authors: Mikiko Watanabe , Renata Risi , Davide Masi , Alessandra Caputi , Angela Balena , Giovanni Rossini , Dario Tuccinardi , Stefania Mariani , Sabrina Basciani , Silvia Manfrini , Lucio Gnessi , Carla Lubrano

In Life Sciences, Public Health

By NCBI Pubmed

The use of food supplements for weight loss purposes has rapidly gained popularity as the prevalence of obesity increases. Navigating through the vast, often low quality, literature available is challenging, as is providing informed advice to those asking for it. Herein, we provide a comprehensive literature revision focusing on most currently marketed dietary supplements claimed to favor weight loss, classifying them by their purported mechanism of action. We conclude by proposing a combination of supplements most supported by current evidence, that leverages all mechanisms of action possibly leading to a synergistic effect and greater weight loss in the foreseen absence of adverse events. Further studies will be needed to confirm the weight loss and metabolic improvement that may be obtained through the use of the proposed combination.

Authors: Michael Strupp , Thomas Brandt

In Medicine and Health Sciences

By NCBI Pubmed

Introduction: Vertigo is not a separate disease process, but a multisensory and sensorimotor syndrome with various etiologies and pathogeneses. It is among the commonest symptoms presented to doctors, with a lifetime prevalence of around 20 to 30%. Patients have often consulted multiple physicians before a diagnosis is made and therapy initiated. Methods: Selective literature research and review of the guidelines of the German Neurological Society. Results: A careful history remains the cornerstone of diagnosis. Once the correct diagnosis is made, specific and effective treatments are available for most peripheral, central, and psychogenic forms of dizziness. Treatment may include medication, physiotherapy, and psychotherapy; a few limited cases may require surgical treatment. The treatment of choice for acute vestibular neuritis is the administration of corticosteroids. Menière's disease is treated with high-dose, long-term betahistine. A new approach to the management of downbeat and upbeat nystagmus, and of episodic ataxia type 2, involves the use of aminopyridines as potassium-channel blockers. Close multidisciplinary cooperation is essential in dizziness, and further multicenter studies are needed.

Authors: Mahendra Kumar Trivedi , Sambhu Charan Mondal , Mayank Gangwar , Snehasis Jana

In Life Sciences, Medicine and Health Sciences, Public Health

By NCBI Pubmed

Background: Herbomineral formulations are momentous in an audience of worldwide by virtue of their holistic approach to life. These formulations are widely used as complementary therapies in immunocompromised patients including cancer. Still, there is the need of cost-effective and safe herbomineral-based formulation that can modulate immune response by the regulation of cytokines cascades. Objective: Current study, we investigated immunomodulatory effect of TEBEH in LPS-induced cytokines expression levels in mouse splenocytes in vitro. Materials and methods: The most effective and safe concentrations of TEBEH were chosen by determining the cell viability of splenocytes using MTT assay. The pro-inflammatory cytokines such as TNF-α, IL-1β, MIP-1α, and IFN-γ were measured in cell supernatants using ELISA. Results: MTT data showed TEBEH formulation was found safe up to 10.53 μg/mL. At noncytotoxic concentrations (0.00001053-10.53 μg/mL), TEBEH significantly (P ≤ 0.001) inhibited the expressions of TNF-α, IL-1β, and MIP-1α in mouse splenocytes as compared with vehicle control. Conclusion: In summary, TEBEH may indeed promote an anti-inflammatory environment by suppression of pro-inflammatory cytokines. These observations indicated that TEBEH has potential effects in downregulating the immune system and might be developed as a useful anti-inflammatory product for various inflammatory disorders. Summary: The present study was undertaken to evaluate an immunomodulatory effect of the herbomineral formulation in LPS-induced mouse splenocytes with the measurement of cytokines expression such as TNF-α, IL-1β, MIP-1α and IFN-γ. The results showed that the expression of TNF-α, IL-1β, and MIP-1α was significantly down-regulated while, IFN-γ was significantly up-regulated in mouse splenocytes. It is hypothesized that modulation of the proinflammatory cytokines might occur via NF-κB pathway. Therefore, the herbomineral test formulation might act as an effective anti-inflammatory and immunomodulatory product, and this can be used as a complementary and alternative treatment for the prevention of various types of inflammatory and auto-immune disorders Abbreviations used: LPS: Lipopolysaccharide, IL: Interleukin; NF-κB: Nuclear factor kappa-B, TNF-α: Tumor necrosis factor alpha, MIP-1α: Macrophage inflammatory protein-1α, IFN-γ: Interferon, MTT: 3-(4,5-diamethyl-2-thiazolyl)-2, 5-diphenyl-2Htetrazolium), ELISA: Enzyme linked immune sorbent assay, ANOVA: Analysis of variance.

Authors: Bailey A.T. Weatherbee , Tongtong Cui , Magdalena Zernicka-Goetz

In Biology

By NCBI Pubmed

Early human post-implantation development involves extensive growth combined with a series of complex morphogenetic events. The lack of precise spatial and temporal control over these processes leads to pregnancy loss. Given the ethical and technical limitations in studying the natural human embryo, alternative approaches are needed to investigate mechanisms underlying this critical stage of human development. Here, we present an overview of the different stem cells and stem cell-derived models which serve as useful, albeit imperfect, tools in understanding human embryogenesis. Current models include stem cells that represent each of the three earliest lineages: human embryonic stem cells corresponding to the epiblast, hypoblast-like stem cells and trophoblast stem cells. We also review the use of human embryonic stem cells to model complex aspects of epiblast morphogenesis and differentiation. Additionally, we propose that the combination of both embryonic and extra-embryonic stem cells to form three-dimensional embryo models will provide valuable insights into cell-cell chemical and mechanical interactions that are essential for natural embryogenesis.

Authors: Queenie Fernandes , Varghese Philipose Inchakalody , Maysaloun Merhi , Sarra Mestiri , Nassiba Taib , Dina Moustafa Abo El-Ella , Takwa Bedhiafi , Afsheen Raza , Lobna Al-Zaidan , Mona O Mohsen , Mariam Ali Yousuf Al-Nesf , Ali Ait Hssain , Hadi Mohamad Yassine , Martin F Bachmann , Shahab Uddin , Said Dermime

In Life Sciences, Medicine and Health Sciences, Medicine, Internal Medicine

By NCBI Pubmed

The emergence of novel and evolving variants of SARS-CoV-2 has fostered the need for change in the form of newer and more adaptive diagnostic methods for the detection of SARS-CoV-2 infections. On the other hand, developing rapid and sensitive diagnostic technologies is now more challenging due to emerging variants and varying symptoms exhibited among the infected individuals. In addition to this, vaccines remain the major mainstay of prevention and protection against infection. Novel vaccines and drugs are constantly being developed to unleash an immune response for the robust targeting of SARS-CoV-2 and its associated variants. In this review, we provide an updated perspective on the current challenges posed by the emergence of novel SARS-CoV-2 mutants/variants and the evolution of diagnostic techniques to enable their detection. In addition, we also discuss the development, formulation, working mechanisms, advantages, and drawbacks of some of the most used vaccines/therapeutic drugs and their subsequent immunological impact.