Role of Nutraceuticals in COVID-19 Mediated Liver Dysfunction.

COVID-19 is known as one of the deadliest pandemics of the century. The rapid spread of this deadly virus at incredible speed has stunned the planet and poses a challenge to global scientific and medical communities. Patients with COVID-19 are at an increased risk of co-morbidities associated with liver dysfunction and injury. Moreover, hepatotoxicity induced by antiviral therapy is gaining importance and is an area of great concern. Currently, alternatives therapies are being sought to mitigate hepatic damage, and there has been growing interest in the research on bioactive phytochemical agents (nutraceuticals) due to their versatility in health benefits reported in various epidemiological studies. Therefore, this review provides information and summarizes the juncture of antiviral, immunomodulatory, and hepatoprotective nutraceuticals that can be useful during the management of COVID-19

Hall Coefficient of Equilibrium Supercurrents Flowing inside Superconductors

We study augmented quasiclassical equations of superconductivity with the Lorentz force, which is missing from the standard Ginzburg-Landau and Eilenberger equations. It is shown that the magnetic Lorentz force on equilibrium supercurrents induces finite charge distribution and the resulting electric field to balance the Lorentz force. An analytic expression is obtained for the corresponding Hall coefficient of clean type-II superconductors with simultaneously incorporating the Fermi-surface and gap anisotropies. It has the same sign and magnitude at zero temperature as the normal state for an arbitrary pairing, having no temperature dependence specifically for the s-wave pairing. The gap anisotropy may bring a considerable temperature dependence in the Hall coefficient and can lead to its sign change as a function of temperature, as exemplified for a model d-wave pairing with a two-dimensional Fermi surface. The sign change may be observed in some high-$T_{c}$ superconductors.Comment: 7 pages, 3 figure

Hepatoprotective role of Cucurbitacin D on benzo[a]pyrene induced liver injury

Background: Epidemiological findings show the strong correlation of co-morbidity factors including smoking with the development and progression of liver cancer. Moreover, benzo[a]pyrene, a main component of tobacco smoke, is extremely carcinogenic and contributes to liver injury as well. Cucurbitacin, chemically classified as triterpenes, have shown diverse biological activities including potent antioxidant, anti-inflammatory and anti-cancer activities. However, their hepatoprotective activities are not completely understood. Objective: In the present study, we investigated the cytoprotective activity of novel analog of cucurbitacin, cucurbitacin D, against benzo[a]pyrene-induced liver injury in human HepG2 cells. Method: Proliferation, clonogenicity, migration, invasion, Western blotting and qPCR analysis were conducted to investigate the cytoprotective effect of cucurbitacin D against benzo[a]pyrene induced liver damage. DCFDA assay was performed to analyze intracellular reactive oxygen species (ROS) level in liver cells. Results: Functional assays showed that cucurbitacin D exhibited cytoprotective effects against dose-dependent growth inhibition by benzo[a]pyrene in human HepG2 cells. This protective effect was likely associated with antioxidant potential of cucurbitacin D, as evidenced by the attenuation of ROS observed by fluorimeter and fluorescence microscopy. Further study is ongoing to examine the effect of cucurbitacin D on oxidative stress markers by employing western blotting and qPCR techniques. Collectively, these results exhibited that cucurbitacin D alleviate benzo[a]pyreneinduced liver injury through its antioxidant effects. Conclusion: These results have demonstrated hepatoprotective effects of cucurbitacin D against benzo[a]pyrene-induced liver damage, rendering it as an effective potential ingredient in food supplements

Development of A Novel Fluorescent NIR Probe for Cancer Bioimaging

Background: Optimal cancer bioimaging is imperative and come in various forms, ranging from screening to detection and surgical guidance. Current imaging tools being used are not cancer-specific and tend to expose patients to radiation. Therefore, there is a crucial need to develop newer and safer imaging modalities. Near InfraRed fluorescence (NIRF) agents have been gaining great attraction for cancer imaging in the past years, because of their high resolution/sensitivity, low cost, and real-time visualization/imaging capabilities without ionizing radiation. Hence, NIRF-based cancer imaging counterpoises some of the obstacles elicited by traditional imaging. Indocyanine green (ICG) is the only FDA approved NIR fluorescent probe for cancer imaging and image guided surgery in clinical settings. However, ICG has several limitations associated with its photostability, high concentration toxicity, and short circulation time. Additionally, internalization of ICG is not cancer-specific. To overcome this, we engineered a novel poly (vinyl pyrrolidone) (PVP) and tannic acid (TA) based nanosystem (PVT) to carry ICG to cancer cells/tissues. Methods: Pursuing the novel nanoimaging approach, our lab has developed PVP-TA-based ICG (PVT-ICG) fluorescent nanoparticles. An IVIS imaging system was used to measure NIR fluorescence of PVT-ICG and its physiochemical properties were further characterized. Moreover, human breast, pancreatic, liver, and prostate cancer cell lines, and cancer tissue microarrays (TMAs) were histochemically stained to assess cancer cell targeting/specificity of PVT-ICG. Results: PVT-ICG indicated particle size and surface charge ideal for cancer cell/tissue delivery. Furthermore, PVT-ICG demonstrated improved fluorescent intensity. Cellular and tissue-binding studies exhibited a superior cancer targeting/specificity achieved from PVT-ICG nanoparticles compared to free ICG dye in all cancer cells/TMAs Conclusion: Collectively, our findings suggest that this NIRF probe PVT-ICG has great potential for becoming a novel and safe imaging modality for various types of cancer cells and tumors which can result in early cancer diagnosis leading to improved disease management

Bone marrow-derived endothelial progenitor cells are a major determinant of nascent tumor neovascularization

Tumors build vessels by cooption of pre-existing vasculature and de novo recruitment of bone marrow (BM)-derived endothelial progenitor cells (EPCs). However, the contribution and the functional role of EPCs in tumor neoangiogenesis are controversial. Therefore, by using genetically marked BM progenitor cells, we demonstrate the precise spatial and temporal contribution of EPCs to the neovascularization of three transplanted and one spontaneous breast tumor in vivo using high-resolution microscopy and flow cytometry. We show that early tumors recruit BM-derived EPCs that differentiate into mature BM-derived endothelial cells (ECs) and luminally incorporate into a subset of sprouting tumor neovessels. Notably, in later tumors, these BM-derived vessels are diluted with non-BM-derived vessels from the periphery, which accounts for purported differences in previously published reports. Furthermore, we show that specific ablation of BM-derived EPCs with alpha-particle-emitting anti-VE-cadherin antibody markedly impaired tumor growth associated with reduced vascularization. Our results demonstrate that BM-derived EPCs are critical components of the earliest phases of tumor neoangiogenesis

Superconducting-coil--resistor circuit with electric field quadratic in the current

It is shown for the first time that the observed [Phys. Lett. A 162 (1992) 105] potential difference Phi_t between the resistor and the screen surrounding the circuit is caused by polarization of the resistor because of the kinetic energy of the electrons of the superconducting coil. The proportionality of Phi_t to the square of the current and to the length of the superconducting wire is explained. It is pointed out that measuring Phi_t makes it possible to determine the Fermi quasimomentum of the electrons of a metal resistor.Comment: 2 pages, 1 figur

Cardiac Magnetic Resonance Radiomics Reveal Differential Impact of Sex, Age, and Vascular Risk Factors on Cardiac Structure and Myocardial Tissue

Background: Cardiovascular magnetic resonance (CMR) radiomics analysis provides multiple quantifiers of ventricular shape and myocardial texture, which may be used for detailed cardiovascular phenotyping. Objectives: We studied variation in CMR radiomics phenotypes by age and sex in healthy UK Biobank participants. Then, we examined independent associations of classical vascular risk factors (VRFs: smoking, diabetes, hypertension, high cholesterol) with CMR radiomics features, considering potential sex and age differential relationships. Design: Image acquisition was with 1.5 Tesla scanners (MAGNETOM Aera, Siemens). Three regions of interest were segmented from short axis stack images using an automated pipeline: right ventricle, left ventricle, myocardium. We extracted 237 radiomics features from each study using Pyradiomics. In a healthy subset of participants (n = 14,902) without cardiovascular disease or VRFs, we estimated independent associations of age and sex with each radiomics feature using linear regression models adjusted for body size. We then created a sample comprising individuals with at least one VRF matched to an equal number of healthy participants (n = 27,400). We linearly modelled each radiomics feature against age, sex, body size, and all the VRFs. Bonferroni adjustment for multiple testing was applied to all p-values. To aid interpretation, we organised the results into six feature clusters. Results: Amongst the healthy subset, men had larger ventricles with dimmer and less texturally complex myocardium than women. Increasing age was associated with smaller ventricles and greater variation in myocardial intensities. Broadly, all the VRFs were associated with dimmer, less varied signal intensities, greater uniformity of local intensity levels, and greater relative presence of low signal intensity areas within the myocardium. Diabetes and high cholesterol were also associated with smaller ventricular size, this association was of greater magnitude in men than women. The pattern of alteration of radiomics features with the VRFs was broadly consistent in men and women. However, the associations between intensity based radiomics features with both diabetes and hypertension were more prominent in women than men. Conclusions: We demonstrate novel independent associations of sex, age, and major VRFs with CMR radiomics phenotypes. Further studies into the nature and clinical significance of these phenotypes are needed

Gene expression variation between distinct areas of breast cancer measured from paraffin-embedded tissue cores

BACKGROUND: Diagnosis and prognosis in breast cancer are mainly based on histology and immunohistochemistry of formalin-fixed, paraffin-embedded (FFPE) material. Recently, gene expression analysis was shown to elucidate the biological variance between tumors and molecular markers were identified that led to new classification systems that provided better prognostic and predictive parameters. Archived FFPE samples represent an ideal source of tissue for translational research, as millions of tissue blocks exist from routine diagnostics and from clinical studies. These should be exploited to provide clinicians with more accurate prognostic and predictive information. Unfortunately, RNA derived from FFPE material is partially degraded and chemically modified and reliable gene expression measurement has only become successful after implementing novel and optimized procedures for RNA isolation, demodification and detection. METHODS: In this study we used tissue cylinders as known from the construction of tissue microarrays. RNA was isolated with a robust protocol recently developed for RNA derived from FFPE material. Gene expression was measured by quantitative reverse transcription PCR. RESULTS: Sixteen tissue blocks from 7 patients diagnosed with multiple histological subtypes of breast cancer were available for this study. After verification of appropriate localization, sufficient RNA yield and quality, 30 tissue cores were available for gene expression measurement on TaqMan(R) Low Density Arrays (16 invasive ductal carcinoma (IDC), 8 ductal carcinoma in situ (DCIS) and 6 normal tissue), and 14 tissue cores were lost. Gene expression values were used to calculate scores representing the proliferation status (PRO), the estrogen receptor status and the HER2 status. The PRO scores measured from entire sections were similar to PRO scores determined from IDC tissue cores. Scores determined from normal tissue cores consistently revealed lower PRO scores than cores derived from IDC or DCIS of the same block or from different blocks of the same patient. CONCLUSION: We have developed optimized protocols for RNA isolation from histologically distinct areas. RNA prepared from FFPE tissue cores is suitable for gene expression measurement by quantitative PCR. Distinct molecular scores could be determined from different cores of the same tumor specimen

Toll-like receptor signaling adapter proteins govern spread of neuropathic pain and recovery following nerve injury in male mice.

BackgroundSpinal Toll-like receptors (TLRs) and signaling intermediaries have been implicated in persistent pain states. We examined the roles of two major TLR signaling pathways and selected TLRs in a mononeuropathic allodynia.MethodsL5 spinal nerve ligation (SNL) was performed in wild type (WT, C57BL/6) male and female mice and in male Tlr2-/-Tlr3-/-, Tlr4-/-, Tlr5-/-, Myd88-/-, Triflps2, Myd88/Triflps2, Tnf-/-, and Ifnar1-/- mice. We also examined L5 ligation in Tlr4-/- female mice. We examined tactile allodynia using von Frey hairs. Iba-1 (microglia) and GFAP (astrocytes) were assessed in spinal cords by immunostaining. Tactile thresholds were analyzed by 1- and 2-way ANOVA and the Bonferroni post hoc test was used.ResultsIn WT male and female mice, SNL lesions resulted in a persistent and robust ipsilateral, tactile allodynia. In males with TLR2, 3, 4, or 5 deficiencies, tactile allodynia was significantly, but incompletely, reversed (approximately 50%) as compared to WT. This effect was not seen in female Tlr4-/- mice. Increases in ipsilateral lumbar Iba-1 and GFAP were seen in mutant and WT mice. Mice deficient in MyD88, or MyD88 and TRIF, showed an approximately 50% reduction in withdrawal thresholds and reduced ipsilateral Iba-1. In contrast, TRIF and interferon receptor null mice developed a profound ipsilateral and contralateral tactile allodynia. In lumbar sections of the spinal cords, we observed a greater increase in Iba-1 immunoreactivity in the TRIF-signaling deficient mice as compared to WT, but no significant increase in GFAP. Removing MyD88 abrogated the contralateral allodynia in the TRIF signaling-deficient mice. Conversely, IFNβ, released downstream to TRIF signaling, administered intrathecally, temporarily reversed the tactile allodynia.ConclusionsThese observations suggest a critical role for the MyD88 pathway in initiating neuropathic pain, but a distinct role for the TRIF pathway and interferon in regulating neuropathic pain phenotypes in male mice