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Ginseng is a group of cosmopolitan plants with more than a dozen species belonging to the genus Panax in the family Araliaceae that has a long history of use in traditional Chinese medicine (TCM). Among the bioactive constituents extracted from ginseng, ginseng saponins are a group of natural steroid glycosides and triterpene saponins found exclusively throughout the plant. Studies have shown that these ginseng saponins play a significant role in exerting multiple therapeutic effects. This review covers their chemical structure and classification, as well as their pharmacological activities, including their regulatory effects on immunomodulation, their anticancer effects, and their functions in the central nervous and cardiovascular systems. The general benefits of ginseng saponins for boosting physical vitality and improving quality of life are also discussed. The review concludes with fruitful directions for future research in the use of ginseng saponins as effective therapeutic agents.

Hypoxia is amongst the most widespread and pressing problems in aquatic environments. Here we demonstrate that fish ( Oryzias melastigma ) exposed to hypoxia show reproductive impairments (retarded gonad development, decrease in sperm count and sperm motility) in F1 and F2 generations despite these progenies (and their germ cells) having never been exposed to hypoxia. We further show that the observed transgenerational reproductive impairments are associated with a differential methylation pattern of specific genes in sperm of both F0 and F2 coupled with relevant transcriptomic and proteomic alterations, which may impair spermatogenesis. The discovered transgenerational and epigenetic effects suggest that hypoxia might pose a dramatic and long-lasting threat to the sustainability of fish populations. Because the genes regulating spermatogenesis and epigenetic modifications are highly conserved among vertebrates, these results may also shed light on the potential transgenerational effects of hypoxia on other vertebrates, including humans. Hypoxia has diverse effects on aquatic life. Wang et al. show that reproductive defects resulting from hypoxia are epigenetically heritable in Japanese rice fish, and that this intergenerational inheritance is accompanied by differential methylation and gene expression in sperm.

Applying the same logistics to PPE allocation would allow PPE providers to manage the distribution of surgical masks on a real-time basis and to recognize the mask holders according to insurance or passport number.5 With the help of data analysis, combining artificial intelligence and cloud technology, public health policy making could be practicable. [...]when it comes to the implementation cost of epidemic prevention policies, Taiwan authorities adopt low-cost, stringent-level strategies compared with other high-income countries, but they still achieved epidemic control in the early outbreak.6 After the 2003 severe acute respiratory syndrome (SARS) outbreak, the Taiwan CDC (TCDC) started transferring registered real-time infectious disease data to this established monitoring system, in which PPE stockpiling platform was used. [...]prior to the official recognition of COVID-19 outbreak,3 PPE databases were subsequently concatenated by UHS to manage resource allocation and logistics when several cases were identified. Specifically, the tracking system expanded the healthcare informatics system that pharmacists were familiar with, and its user-friendly interfaces for PPE providers and consumers helped expedite distribution processes.5 The UHS and the TCDC have also promoted the system to increase the distribution channels, within which government offices may also allot masks to lessen the burden on healthcare providers. Because masks alone are not effective without combining infection-control measures,7 we recommend this integrative platform for the maintenance of more PPE stockpiles, including critical infection-control equipment to reduce iatrogenic SARS-CoV-2 exposure.

Background Angiotensin II (ANGII) and its receptor (AGTR1) have been proposed as significant contributors to metastasis in multiple cancers. Further, high AGTR1 levels are associated with poor epithelial ovarian cancer (EOC) outcomes. However, the mechanistic basis for these effects is unknown. Recent studies have suggested that ovarian cancer metastasis is highly dependent on the formation of multicellular spheroids (MCS). To understand the associations between the ANGII/AGTR1 pathway and cancer outcomes, we evaluated the effects of ANGII on MCS formation by ovarian cancer cells and used a proteomic approach to analyze the mechanistic basis. Methods We used the data from the GENT database and immunohistochemistry staining to assess the AGTR1 expression in epithelial ovarian cancer (EOC) patients and to assess its role in cancer progression. Colony formation assay, 3D culture assay, and transwell assays were used to analyze the effect of ANGII on the MCS formation and cell migration. The signaling pathways of AGTR1 and transactivation of epidermal growth factor receptor (EGFR) transactivation were investigated by the western blotting analysis. Xenograft models were used to determine the role of AGTR1 in ovarian cancer metastasis. ANGII release from ovarian cancer cells and ANGII levels in the EOC ascites fluid were measured by immunoassay. A shotgun proteomic approach was used to explore the detail molecular mechanism. Modulation of lipid desaturation and endoplasmic reticulum stress were verified by the in vitro and in vivo functional assays. Results AGTR1 expression was negatively correlated with EOC prognosis. AGTR1activation significantly enhanced the MCS formation and cell migration. ANGII triggered both of the classical AGTR1 pathway and the EGFR transactivation. ANGII administration increased peritoneal metastasis. In addition, ovarian cancer cells secreted ANGII and enhanced cancer metastasis in a positive feedback manner. Based on the proteomic data, lipid desaturation was activated by induction of stearoyl-CoA desaturase-1 (SCD1), which suggests that inhibition of SCD1 may significantly reduce MCS formation by increasing endoplasmic reticulum stress. Conclusions ANGII promotes MCS formation and peritoneal metastasis of EOC cells. AGTR1 activation increases the lipid desaturation via SCD1 upregulation, which ultimately reduces endoplasmic reticulum stress in MCS. This mechanism explained the association between high levels of AGTR1 and poor clinical outcomes in EOC patients.

Quantitative systems pharmacology (QSP) approaches have been increasingly applied in the pharmaceutical since the landmark white paper published in 2011 by a National Institutes of Health working group brought attention to the discipline. In this perspective, we discuss QSP in the context of other modeling approaches and highlight the impact of QSP across various stages of drug development and therapeutic areas. We discuss challenges to the field as well as future opportunities.

Mild Traumatic Brain Injury (MTBI) patients with persistent headaches are known to have diminished supraspinal modulatory connectivity from their prefrontal cortices. Repetitive transcranial magnetic stimulation (rTMS) is able to alleviate MTBI-related headache (MTBI-HA). This functional magnetic resonance imaging (fMRI) study assessed supraspinal correlates associated with the headache analgesic effect of rTMS at left prefrontal cortex (LPFC), hypothesizing real rTMS would significantly increase modulatory functions at LPFC in comparison to sham treatment. Subjects with MTBI-HA were randomized to receive either real or sham rTMS treatments and subjected to pre- and post-treatment resting state and evoked heat-pain fMRI as described in a prior study. Real rTMS consisted of 2000 pulses delivered at 10 Hz and 80% of the resting motor threshold at left dorsolateral prefrontal cortex, whereas sham treatment was delivered with same figure-of-eight coil turned 180 degrees. Follow-up fMRI was performed one-week post-treatment. All fMRI data was processed using BrainVoyager QX Software. 14 subjects receiving real and 12 subjects receiving sham treatments completed the study. The REAL group demonstrated significant ( P  < 0.02) decreases in headache frequency and intensity at one week following treatment. fMRI scans in the REAL group showed increased evoked heat pain activity ( P  < 0.002) and resting functional connectivity ( P  < 0.0001) at the LPFC after rTMS. Neither this significant analgesic effect nor these fMRI findings were seen in the sham group. Sham treatment was, however, associated with a decrease in resting state activity at the LPFC ( P  < 0.0001). This study correlates the demonstrated analgesic effect of rTMS in the treatment of MTBI-HA with enhanced supraspinal functional connectivity in the left prefrontal cortex, which is known to be involved in “top-down” pain inhibition along the descending midbrain-thalamic-cingulate pathway. Trial Registration : This study was registered on September 24, 2013, on ClinicalTrials.gov with the identifier: NCT01948947. https://clinicaltrials.gov/ct2/show/NCT01948947 .

Despite recommendations for vaccinating adults and widespread availability of immunization services (e.g., pharmacy venues, workplace wellness clinics), vaccination rates in the United States remain low. The U.S. National Adult Immunization Plan identified the development of quality measures as a priority and key strategy to address low adult vaccination coverage rates. The use of quality measures can provide incentives for increased utilization of preventive services. To address the lack of adult immunization measures, the National Adult and Influenza Immunization Summit, a coalition of adult immunization partners led by the Immunization Action Coalition, Centers for Disease Control and Prevention, and National Vaccine Program Office, spearheaded efforts to (1) identify gaps and priorities in adult immunization quality performance measurement; (2) explore feasibility of data collection on adult immunizations through pilot testing and engaging stakeholders; and (3) develop and test quality measure specifications. This paper outlines the process by which a public-private partnership drove the development of two adult immunization performance measures—an adult immunization status measure for influenza, tetanus and diphtheria (Td) and/or tetanus toxoid, reduced diphtheria toxoid, and acellular pertussis (Tdap), herpes zoster and pneumococcal vaccines, and a prenatal immunization status measure for influenza and Tdap vaccinations in pregnant women. These measures have recently been added to the 2019 Healthcare Effectiveness Data and Information Set (HEDIS®), a widely used set of performance measures reportable by private health plans.

G protein‐coupled receptors (GPCRs) are the most common and important drug targets. However, >70% of GPCRs are undruggable or difficult to target using conventional chemical agonists/antagonists. Small nucleic acid molecules, which can sequence‐specifically modulate any gene, offer a unique opportunity to effectively expand drug targets, especially those that are undruggable or difficult to address, such as GPCRs. Here, the authors report  for the first time that small activating RNAs (saRNAs) effectively modulate a GPCR for cancer treatment. Specifically, saRNAs promoting the expression of Mas receptor (MAS1), a GPCR that counteracts the classical angiotensin II pathway in cancer cell proliferation and migration, are identified. These saRNAs, delivered by an amphiphilic dendrimer vector, enhance MAS1 expression, counteracting the angiotensin II/angiotensin II Receptor Type 1 axis, and leading to significant suppression of tumorigenesis and the inhibition of tumor progression of multiple cancers in tumor‐xenografted mouse models and patient‐derived tumor models. This study provides not only a new strategy for cancer therapy by targeting the renin‐angiotensin system, but also a new avenue to modulate GPCR signaling by RNA activation. Small activating RNAs (saRNAs) targeting MAS1, delivered by an amphiphilic dendrimer (AD) vector, enhance MAS1 expression and counteract the angiotensin II pathway in cancer cells, leading to significantly suppressed tumorigenesis and inhibited tumor progression. This saRNA approach opens a new avenue of using saRNA to target undruggable G protein‐coupled receptors for drug development and disease treatment.

A cross‐industry survey was conducted to assess the landscape of preclinical quantitative systems pharmacology (QSP) modeling within pharmaceutical companies. This article presents the survey results, which provide insights on the current state of preclinical QSP modeling in addition to future opportunities. Our results call attention to the need for an aligned definition and consistent terminology around QSP, yet highlight the broad applicability and benefits preclinical QSP modeling is currently delivering.

High failure rates in clinical trials for neurodegenerative disorders such as Alzheimer’s disease have been linked to an insufficient predictive validity of current animal-based disease models. This has created an increasing demand for alternative, human-based models capable of emulating key pathological phenotypes in vitro . Here, a three-dimensional Alzheimer’s disease model was developed using a compartmentalized microfluidic device that combines a self-assembled microvascular network of the human blood-brain barrier with neurospheres derived from Alzheimer’s disease-specific neural progenitor cells. To shorten microfluidic co-culture times, neurospheres were pre-differentiated for 21 days to express Alzheimer’s disease-specific pathological phenotypes prior to the introduction into the microfluidic device. In agreement with post-mortem studies and Alzheimer’s disease in vivo models, after 7 days of co-culture with pre-differentiated Alzheimer’s disease-specific neurospheres, the three-dimensional blood-brain barrier network exhibited significant changes in barrier permeability and morphology. Furthermore, vascular networks in co-culture with Alzheimer’s disease-specific microtissues displayed localized β-amyloid deposition. Thus, by interconnecting a microvascular network of the blood-brain barrier with pre-differentiated neurospheres the presented model holds immense potential for replicating key neurovascular phenotypes of neurodegenerative disorders in vitro .