Notes

Co-overexpression regarding RIOK1 and AKT1 like a prognostic danger factor in glioma.
HF has pathophysiologic sex-specific distinctions, suggesting that sex-specific preventive strategies may be beneficial. Pharmacologic agents that have shown benefit in reducing the risk of HF address the pathobiology underpinning these sex-specific risk factors. The implementation of pharmacologic therapies for primary prevention of HF needs to consider a risk-based model. Current pharmacotherapies hold mechanistic promise for the primary prevention of HF in females and gender and sexual minorities, although research is needed to understand the specific populations most likely to benefit. There are significant systemic barriers to the equitable provision of HF primary prevention.
Despite its prevalence and well-documented impact on population health, obesity has not emerged as a strong independent risk factor for cardiovascular disease after control for intermediate risk factors. The purpose of this brief narrative review is to highlight results from imaging studies that have not only documented the remarkable heterogeneity of body fat topography but also the importance of visceral adiposity as a key body fat depot associated with cardiovascular disease risk and type 2 diabetes.

Simple tools are also discussed in order to refine cardiometabolic risk assessment in persons with overweight/obesity. It is proposed that four lifestyle vital signs should be considered in clinical practice to improve discrimination of health risk in individuals with overweight/obesity waist circumference as a simple marker of abdominal adiposity, cardiorespiratory fitness, overall diet quality, and level of reported physical activity. Heterogeneity of obesity is proposed as an example of a condition that would benefit from a precision lifestyle medicine approach.
Simple tools are also discussed in order to refine cardiometabolic risk assessment in persons with overweight/obesity. It is proposed that four lifestyle vital signs should be considered in clinical practice to improve discrimination of health risk in individuals with overweight/obesity waist circumference as a simple marker of abdominal adiposity, cardiorespiratory fitness, overall diet quality, and level of reported physical activity. Heterogeneity of obesity is proposed as an example of a condition that would benefit from a precision lifestyle medicine approach.
Knee osteoarthritis (OA) is a disease affecting all the neighboring articular tissues including the infrapatellar fat pad (IPFP). Although not yet as widely studied as other tissues in the knee, the IPFP has been recognized to have important metabolic activities and is a key player in OA.

In this commentary, we will briefly describe the different methodologies employed for the MRI morphological measurement of this tissue and depict the findings in regard to OA.

The morphology of this tissue, monitored mainly with the use of magnetic resonance imaging (MRI), demonstrates changes during OA. However, studies of the IPFP morphological alterations and their association with the OA process have shown conflicting results, including a detrimental or beneficial role or no role at all. Although many reasons could explain such mixed findings, one might be the different methodologies used for the MRI measurement of area, volume, or signal intensity. In addition, several techniques are also employed for measuring the volume and signal intensity. An additional level of complexity is related to the presence within the IPFP of two different types of signal intensities, hyper-intensity, and hypo-intensity.

A consensus of a procedure to measure the morphology of the IPFP is urgently needed to fully appreciate the role of this tissue in the pathology of OA, as well as its uses for clinical decision-making.
A consensus of a procedure to measure the morphology of the IPFP is urgently needed to fully appreciate the role of this tissue in the pathology of OA, as well as its uses for clinical decision-making.
Valproic acid (VPA) toxicity commonly results in a self-limited state of CNS depression that is managed with supportive care and levocarnitine. In massive overdose, patients can develop toxic encephalopathy, shock, multisystem organ failure, and death. We present a case with relevant toxicokinetics of a patient presenting with a profoundly elevated VPA concentration resulting in survival, treated with supportive care including high-dose continuous venovenous hemodiafiltration (CVVHDF).

A 17-year-old female presented to an emergency department after being found unresponsive at home with concern for massive VPA ingestion. She arrived obtunded and hypotensive with initial VPA concentration of 2226 mg/L, estimated 9 h post-ingestion. Her early hospital course was marked by hypotension requiring multiple vasopressors, and her workup was notable for multiple severe metabolic derangements. High-dose CVVHDF was initiated upon transfer to a tertiary children's hospital with the aim to enhance VPA removal and normatration was 1071 mg/L. Apparent half-life of VPA improved modestly with extracorporeal treatment, but her metabolic derangements and hemodynamic instability corrected rapidly. Her clinical course was complicated by necrotizing pancreatitis, pancytopenia requiring transfusions of multiple cell lines, coma, and seizures. She ultimately recovered with normal neurological function.
Cellular responses following cerebral ischemia/reperfusion injury are critical to recovery and survival after ischemic stroke. Understanding of these cellular responses can help the design of therapies to protect brain tissue and promote recovery after stroke. One of these cellular responses may be mediated by the AKT (protein kinase B) signal transduction pathway. This study was aimed to investigate the cerebral ischemia-induced alterations of AKT signaling and the upstream molecular pathways.

We modeled cerebral ischemia by middle cerebral artery occlusion in 2-3-month-old male C57BL/6J mice and then analyze the brain samples by using quantitative Western blots and phosphorylation/activation-dependent kinase antibodies. Cerebral ischemia was confirmed by staining of brain slices with 1% 2,3,5-triphenyltetrazolium chloride (TTC) and Nissl, as well as neurological assessments of the mice 24h after ischemia-reperfusion surgery.

We found marked downregulation of AKT within 12h of cerebral ischemia/reperfusion, which leads to overactivation of glycogen synthase kinase-3β (GSK-3β). Furthermore, we found that the downregulation of AKT was mediated by downregulation of mTORC2 (the complex 2 of the mechanistic target of rapamycin) instead of its common upstream kinases, phosphatidylinositol 3-kinase and phosphoinositide-dependent kinase-1.

Our findings provide new insight into the cellular responses to ischemia/reperfusion brain injury and will help develop new treatments targeting the AKT signaling pathway for the treatment of ischemic stroke.
Our findings provide new insight into the cellular responses to ischemia/reperfusion brain injury and will help develop new treatments targeting the AKT signaling pathway for the treatment of ischemic stroke.The world is grappling with an unprecedented public health crisis COVID-19 pandemic caused by the novel coronavirus SARS-CoV-2. Due to the high transmission/mortality rates and socioeconomic impacts of the COVID-19, its control is crucial. In the absence of specific treatment, vaccines represent the most efficient way to control and stop the pandemic. Many companies around the world are currently making efforts to develop the vaccine to combat COVID-19. This review outlines key strategies for generating SARS-CoV-2 vaccine candidates, along with the mechanism of action, advantages, and potential limitations of each vaccine. The use of nanomaterials and nanotechnology for COVID-19 vaccines development will also be discussed.
Fruit morphology traits are important commercial traits that directly affect the market value. However, studying the genetic basis of these traits in un-explored botanical groups is a fundamental objective for crop genetic improvement through marker-assisted breeding.

In this study, a quantitative trait loci (QTLs) mapping strategy was used for dissecting the genomic regions of fruit linked morphological traits by single nucleotide polymorphism (SNP) based cleaved amplified polymorphism sequence (CAPS) molecular markers. Next-generation sequencing was done for the genomic sequencing of two contrasted melon lines (climacteric and non-climacteric), which revealed 97% and 96% of average coverage over the reference melon genome database, respectively. A total of 57.51% non-synonymous SNPs and 42.49% synonymous SNPs were found, which produced 149 sets of codominant markers with a 24% polymorphism rate. Total 138-F
derived plant populations were genotyped for linkage mapping and composite interval mapping baside the reference insights for fine QTL mapping and candidate gene(s) mining through molecular genetic breeding approaches aimed at developing the new varieties.One of the leading causes of cancer-related deaths worldwide is breast cancer, among which triple-negative breast cancer (TNBC) is the most malignant and lethal subtype. This cancer accounts for 10-20% of all breast cancer deaths. Proliferation, tumorigenesis, and prognosis of TNBC are affected when the androgen receptor (AR) is not expressed, and it is classified as quadruple negative breast cancer (QNBC). Cell Cycle inhibitor Non-coding RNAs, such as microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular RNAs (circRNAs), play a significant role in tumorigenesis by virtue of their oncogenic and tumor-suppressive properties. To regulate tumorigenesis, miRNAs interact with their target mRNAs and modulate their expression, whereas lncRNAs can either act alone or interact with miRNAs or other molecules through various signaling pathways. Conversely, circRNAs regulate tumorigenesis by acting as miRNA sponges predominantly. Recently, non-coding RNAs were studied comprehensively for their roles in tumor proliferation, progression, and metastasis. As a result of existing studies and research progress, non-coding RNAs have been implicated in TNBC, necessitating their use as biomarkers for future diagnostic applications. In this review, the non-coding RNAs are explicitly implicated in the regulation of breast cancer, and their cross-talk between TNBC and QNBC is also discussed.
In this study, the optimized niosomal formulation containing paclitaxel using non-ionic surfactants and cholesterol was designed and its cytotoxic effects against different breast cancer cell lines and apoptosis gene expression analysis were also investigated.

Due to enhancing equation variables, the Box-Behnken method has been applied. Lipid/drug molar ratio, the amounts of Span 60, and cholesterol were selected as the target for optimization. The particle size of niosome loaded paclitaxel and entrapment efficiency proportion have been considered in the role of dependent variables. Then the cytotoxic activity of the optimized formulation was evaluated using an MTT assay against different breast cancer cell lines including MCF-7, T-47D, SkBr3, and MDA-MB-231. The expression level of Bax and Bcl-2 apoptosis genes was determined by Real-Time PCR. In this study, the optimized niosomal formulation revealed that the synthesized niosomes had a spherical appearance and had an average size of 192.73 ± 5.50nm so that the percentage of drug loading was 94.
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