Biology subjects

Ying, W.

Publications and source records attributed to Ying, W..

13 recordsLinked to original sources

bioRxiv2018

Effects of age on the green autofluorescence of the skin and fingernails of healthy persons

Our recent studies have suggested that altered Pattern of Autofluorescence (AF) of skin and fingernails are novel biomarkers of multiple major diseases. The age of all of the subjects in these studies ranges from 50 to 80 years of old. For future studies on the potential diagnostic value of green AF for age-independent diseases, it is required to answer the following question: Are there differences in the green AF of healthy persons of various age populations? In our current study, we determined the green AF of the skin and fingernails of healthy persons in several age populations, showing significant age dependence of the AF: First, the green AF intensity of the age group between 15 to 20 years of old is significantly higher than that of the age group between 50 to 80 years of old at both right and left Centremetacarpus, right Dorsal Centremetacarpus, and right Dorsal Index Finger. Second, for the green AF intensity of the age groups of 15 to 20 years of old, 60 to 70 years of old, 70 to 80 years of old, and 81 to 85 years of old, the green AF intensity is negatively correlated with the age at both right and left Centremetacarpus and right Dorsal Centremetacarpus. Collectively, our study has provided first evidence indicating the age dependence of the AF intensity of humans skin, which has established essential basis for the studies that determine the diagnostic value of the green AF for the age-independent diseases.

physiology↗

bioRxiv2018

Green autofluorescence intensity of skin and fingernails: A novel biomarker for non-invasive evaluation of pathological state of blood vessels

Stroke and myocardial infarction (MI) are two leading causes of death around the world. It is of great significance to establish novel and non-invasive approaches for evaluating pathological state of blood vessels, so that early interventions may be carried out to prevent incidence of stroke or MI. Our recent studies have suggested that altered Pattern of Autofluorescence (AF) of skin and fingernails are novel biomarkers of acute ischemic stroke (AIS) and MI. In particular, our studies have shown characteristic increases in the green AF intensity of the fingernails and certain regions of the skin of AIS patients and MI patients. By determining the skins green AF of the Healthy Group, the Low-Risk Group for Developing AIS, and the High-Risk Group for Developing AIS, our current study has indicated that the green AF intensity in the fingernails and certain regions of the skin, including the right and left Dorsal Index Fingers, Ventroforefingers, Dorsal Antebrachium and Index Fingernails as well as right Dorsal Centremetacarpus, is highly correlated with the risk to develop AIS. There is also evidence suggesting that increased oxidative stress may account for the increased AF intensity in the Low-Risk Group for Developing AIS and the High-Risk Group for Developing AIS. These findings have suggested that the green AF intensity of the fingernails and certain regions of the skin is a novel biomarker for non-invasive evaluation of the pathological state of blood vessels and the risk for developing AIS or MI.

pathology↗

bioRxiv2018

Decreased green autofluorescence intensity of lung parenchyma is a potential non-invasive diagnostic biomarker for lung cancer

Early and non-invasive diagnosis is critical for enhancing the survival rates of lung cancer. In current study we determined the green autoflorescence (AF) of the pulmonary parenchyma of lung cancer patients, using 488 nm and 500 - 550 nm as excitation wavelength and emission wavelength, respectively. Our study has suggested that decreased green AF intensity of pulmonary parenchyma may be a potential diagnostic biomarker for lung cancer: First, the green AF intensity of the cancerous tissues is less than 40% of those of distant non-neoplastic tissues and peri-neoplastic tissues; second, the green AF intensity of both the distant non-neoplastic tissues and cancerous tissues of squamous carcinoma is significantly lower than that of adenocarcinoma; third, the AF intensity of the peri-neoplastic tissues of the lung cancer patients is negatively correlated with the stages of lung cancer; and fourth, our study on the AF spectrum of pulmonary parenchyma has suggested that the AF may result from the AF of the keratins or FAD of the pulmonary parenchyma. Collectively, our study has suggested that decreased green AF intensity of pulmonary parenchyma may become a novel biomarker for non-invasive diagnosis of lung cancer. The green AF intensity may also be used to non-invasively differentiate squamous carcinoma and adenocarcinoma, as well as the stages of lung cancer. Moreover, our diagnostic approach for lung cancer may be used for image-guided surgery of lung cancer for lesions that have not been identified by CT.

biophysics↗

bioRxiv2018

Extracellular Degradation into Adenosine and the Activities of Adenosine Kinase and AMPK Mediate Extracellular NAD+-produced increases in the Adenylate Pool of BV2 Microglia under Basal Conditions

Cumulating evidence has indicated NAD+ deficiency as a common central pathological factor of multiple diseases and aging. NAD+ supplement is highly protective in various disease and aging models, while two key questions remain unanswered: 1) Does extracellular NAD+ also produce its effects through its degradation product adenosine? 2) Does extracellular NAD+ produce the protective effects by affecting cells under pathological insults only, or by affecting both normal cell and cells under pathological insults? Since extracellular NAD+ can be degraded into adenosine, and endogenous adenosine levels are in the nanomolar range under physiological conditions, extracellular NAD+ may produce its effects through its degradation into adenosine. In this study we used BV2 microglia as a cellular model to test our hypothesis that NAD+ treatment can increase the intracellular adenylate pool under basal conditions through its extracellular degradation into adenosine. Our study has shown that extracellular NAD+ increases the adenylate pool of BV2 microglia under basal conditions through its degradation into adenosine that enters the cells through equilibrative nucleoside transporters. The intracellular adenosine is converted to AMP by adenosine kinase, which increases intracellular ATP by both activating AMPK and increasing ADP that drives mitochondrial FoF1-ATP synthase. Collectively, our study has suggested that extracellular NAD+ can enhance defensive capacity of normal cells through a novel pathway, which includes extracellular NAD+ degradation into adenosine and the activities of adenosine kinase and AMPK. Our findings have also suggested that NAD+ administration in various disease and aging models may significantly affect the microglia under basal conditions.

cell biology↗

bioRxiv2018

Distinct Patterns of the Autofluorescence of Body Surface: Potential Novel Diagnostic Biomarkers for Stable Coronary Artery Disease and Myocardial Infarction

Searches for new biomarkers of stable coronary artery disease (SCAD) and myocardial infarction (MI) are critical for therapeutic efficacy of the diseases. In this study we tested our hypothesis that distinct patterns of autofluorescence (AF) of skin and fingernails may become novel diagnostic biomarkers for MI and SCAD. Our study has indicated that SCAD and MI have distinct patterns of AF of their body surface: First, the AF intensity of the MI patients is significantly higher than that of the Healthy and Low-Risk group in their right and left Centremetacarpus, Ventroforefinger, Dorsal Index Finger and Ventribrachium, while the AF intensity of the SCAD patients is significantly higher than that of the Healthy and Low-Risk group in their right and left Index Fingernails and Dorsal Antebrachium; and second, the AF asymmetry of the MI patients is significantly higher than that of the Healthy and Low-Risk group in their Centremetacarpus, Ventroforefinger, Index Fingernails and Dorsal Antebrachium, while the AF asymmetry of the SCAD patients is significantly higher than that of the Healthy and Low-Risk group in their Ventroforefinger, Dorsal Index Finger, Dorsal Centremetacarpus and Index Fingernails. Moreover, the AF pattern of acute ischemic stroke is markedly different from those of SCAD and MI. The oxidative stress in the plasma of the MI and SCAD patients may cause the increased AF by altering the AF of keratins. Collectively, our study has indicated that SCAD and MI patients have distinct patterns of AF changes, which may become novel diagnostic biomarkers for SCAD and MI.

biophysics↗

bioRxiv2018

LFAQ: towards unbiased label-free absolute protein quantification by predicting peptide quantitative factors

Mass spectrometry (MS) has become a prominent choice for large-scale absolute protein quantification, but its quantification accuracy still has substantial room for improvement. A crucial issue is the bias between the peptide MS intensity and the actual peptide abundance, i.e., the fact that peptides with equal abundance may have different MS intensities. This bias is mainly caused by the diverse physicochemical properties of peptides. Here, we propose a novel algorithm for label-free absolute protein quantification, LFAQ, which can correct the biased MS intensities by using the predicted peptide quantitative factors for all identified peptides. When validated on datasets produced by different MS instruments and data acquisition modes, LFAQ presented accuracy and precision superior to those of existing methods. In particular, it reduced the quantification error by an average of 46% for low-abundance proteins.

bioinformatics↗

bioRxiv2018

Selectively increased autofluorescence at fingernails and certain regions of skin: A potential novel diagnostic biomarker for Parkinson disease

Diagnosis of Parkinsons disease (PD) mainly relies on the judgment of experienced neurologists on the clinical symptoms of patients. Quantitative and specific biomarker tests for PD is greatly needed. In this study we tested our hypothesis that increased autofluorescence (AF) of skin and fingernails may become a novel diagnostic biomarker for PD. Our study has indicated that PD patients have a distinct pattern of AF changes, compared with that of acute ischemic stroke (AIS) patients: First, the AF intensity of PD patients in the fingernails and a part of the examined regions of skin is significantly higher than that of the healthy and Low-Risk group, while the AF intensity of AIS patients is significantly higher than that of the healthy and Low-Risk group in most regions examined; second, there is AF asymmetry at the index fingernails and two regions of the skin of PD patients, while there is AF asymmetry at all examined regions of AIS patients; and third, both the AF intensity and AF asymmetry at Centremetacarpus of PD patients is significantly lower than those of AIS patients. The increased AF may result from the altered keratins AF induced by the oxidative stress in the plasma of PD patients. Collectively, our study has indicated that PD patients have a distinct pattern of AF changes compared with those of healthy and Low-Risk persons as well as AIS patients, which may become a novel diagnostic biomarker for PD.

neuroscience↗

bioRxiv2018

Selectively increased autofluorescence at certain regions of skin may become a novel diagnostic biomarker for lung cancer

Early diagnosis is critical for improving the 5-year survival rate of lung cancer patients. Our current study tested our hypothesis that increased autofluorescence (AF) of skin and nails may become a novel diagnostic biomarker of lung cancer, which has generated the following findings: First, our study on a mouse model of lung cancer has shown that development of lung cancer led to a marked increase in the epidermal green AF of the mice. Second, the AF intensity of the untreated lung cancer patients was significantly higher than that of the healthy persons and the pulmonary infection patients at certain examined locations of the skin and fingernails. Third, the ‘Pattern of AF’ of healthy controls, pulmonary infection patients and untreated lung cancer patients was markedly different from each other. Fourth, when the number of the locations with increased AF was used as the sole diagnostic parameter, our ROC analysis showed that the AUC was 0.9067 for differentiating the healthy controls and the untreated lung cancer patients. Collectively, our study has indicated that development of lung cancer is sufficient to induce increases in the epidermal green AF of both mice and human subjects. Our study has also indicated that the ‘Pattern of AF’ of lung cancer patients could become a novel biomarker of lung cancer, which holds great promise for non-invasive, rapid and economic diagnosis and screening of lung cancer.Competing Interest StatementThe authors have declared no competing interest.View Full Text

cancer biology↗

bioRxiv2018

Asymmetric increases in the intensity of the green autofluorescence of ischemic stroke patients’ skin and fingernails: A novel diagnostic biomarker for ischemic stroke

AbstractEarly and economical diagnosis of acute ischemic stroke (AIS) is pivotal for therapeutic efficacy, particularly for the settings where medical imaging resource is deficient. We have obtained evidence supporting our hypothesis that collective properties of the green autofluorescence (AF) of the fingernails and certain skins positions may be a novel diagnostic biomarker for AIS: Both the green AF intensity and AF asymmetry of the AIS patients in their Index Fingernails and most examined skins positions were significantly higher than that of the healthy subjects and the Non-AIS subjects. ROC analyses and machine learning-based analyses on the AF properties showed that AUC was 0.93 and 0.87, respectively, for differentiating the AIS patients from the healthy subjects and for differentiating the AIS patients from the Non-AIS subjects. The AIS patients had significantly higher AF intensity and AF asymmetry at several examined positions, compared to those of the patients of Parkinsons disease, pulmonary infection and transient ischemic attack. The AUC was 0.79 - 0.88 for differentiating AIS patients from each of these diseases. There was evidence suggesting that the AF originates from keratins. Collectively, our study has indicated that the characteristic AISs Pattern of AF is a novel diagnostic biomarker for the disease. The Pattern of AF Technology holds excellent potential to become a new non-invasive, label-free and economical diagnostic approach for AIS, which is particularly valuable when MRI or CT imaging resource is deficient.

neuroscience↗

bioRxiv2018

Oxidative Stress Mediates UVC-Induced Increases in Epidermal Autofluorescence of C57 Mouse Ears

Our recent study has reported that UV-induced epidermal autofluorescence (AF) can be used as a novel biomarker for predicting UV-induced skin damage, which is originated from UV-induced, cysteine protease-mediated keratin 1 degradation. A key question regarding these findings is: Does oxidative stress play a significant role in the UV-induced epidermal AF and keratin 1 proteolysis? In our current study, we administered the widely used antioxidant N-acetyl cysteine (NAC) into the skin of mouse ears to test our hypothesis that oxidative stress mediates UV-induced increases in the epidermal AF and keratin 1 degradation. Our study has shown that NAC administration can significantly attenuate the UVC-induced AF increases. The NAC administration can also significantly decrease the UVC-induced keratin 1 degradation. Collectively, our findings have indicated that the oxidative stress induced by UVC is causative to the UVC-induced increases in epidermal AF and keratin 1 proteolysis. Moreover, since oxidative stress is significantly increased in multiple regions of the body in several major diseases, the oxidative stress-induced increases in epidermal AF may become a novel biomarker for diagnosis of major diseases.

biochemistry↗

bioRxiv2018

Increased green autofluorescence is a marker for non-invasive prediction of H2O2-induced cell death and decreases in the intracellular ATP of HaCaT cells

Since oxidative stress plays important pathological roles in numerous diseases, it is of both critical theoretical and clinical significance to search for the approaches for predicting oxidative damage. Cellular models have great value for studying oxidative damage, which would be significantly promoted if non-invasive approaches for predicting oxidative damage can be established without the need of exogenous probes. In our current study, we tested our hypothesis that changes of the autofluorescence (AF) of cells may be used for predicting oxidative cellular damage. Our study found that H2O2 dose-dependently increased the green AF of HaCaT keratinocyte cell line at non-nuclear regions assessed at 1 hr or 3 hrs after the H2O2 exposures, while H2O2 did not affect the green AF of other cell types tested in our study, including PC 12 cells and BV2 microglia. We further found that the increases in the AF of HaCaT cells are highly correlated with the H2O2-induced increases in early-stage apoptosis, late-stage apoptosis and necrosis assessed at 18 hrs after the H2O2 exposures, which are also negatively correlated with the intracellular ATP levels of the H2O2-treated cells assessed at 18 hrs after the H2O2 exposures. Collectively, our study has suggested that increased AF may become the first endogenous marker for non-invasive prediction of oxidative damage selectively for such cell types as HaCaT cells. Compared with traditional approaches, our method may have significant value for studying oxidative damage of keratinocytes with significantly higher efficiency and lower cost.

cell biology↗

bioRxiv2018

Inhibition of mitochondrial ferredoxin 1 (FDX1) prevents adaptation to proteotoxic stress

The mechanisms used by cancer cells to resist the severe disruption in protein homeostasis caused by proteasome inhibitors remain obscure. Here, we show this resistance correlates with a metabolic shift from glycolysis to oxidative phosphorylation (OXPHOS). Employing small molecule screens, we identified a striking overlap between compounds that preferentially impede the growth of proteasome inhibitor-resistant cancer cells and those that block the growth of high OXPHOS cells. Elesclomol potently exhibits both characteristics. Using genome-wide CRISPR/Cas9-based screening, in vitro validation and NMR spectroscopy we identify mitochondrial protein ferredoxin 1 (FDX1), a critical component of mitochondrial iron-sulfur (Fe-S) cluster biosynthesis, as the primary target of elesclomol. In a mouse model of multiple myeloma, inhibition of FDX1 with elesclomol significantly attenuated the emergence of proteasome inhibitor-resistance and markedly prolonged survival. Our work reveals that the mitochondrial Fe-S cluster pathway is a targetable vulnerability in cancers that are resistant to increased proteotoxic burden.

cancer biology↗

bioRxiv2017

UV-Induced Keratin 1 Proteolysis Mediates UV-Induced Skin Damage

Keratins play critical roles in intermediate filament formation, inflammatory responses and cellular signaling in epithelium. While keratins is a major epidermal fluorophore, the mechanisms underlying the autofluorescence (AF) of keratins and its biomedical implications have remained unknown. Our study used mouse skin as a model to study these topics, showing that UV dose-dependently induced increases in green AF at the spinous layer of the epidermis of mouse within 6 hr of the UV exposures, which may be used for non-invasive prediction of UV-induced skin damage. The UV-induced AF appears to be induced by cysteine protease-mediated keratin 1 proteolysis: 1) UV rapidly induced significant keratin 1 degradation; 2) administration of keratin 1 siRNA largely decreased the UV-induced AF; and 3) administration of E-64, a cysteine protease inhibitor, significantly attenuated the UV-induced AF and keratin 1 degradation. Our study has also suggested that the UV-induced keratin 1 proteolysis may be a novel crucial pathological factor in UV-induced skin damage, which is supported by both the findings that indicate critical biological roles of keratin 1 in epithelium and our observation that prevention of UV-induced keratin 1 proteolysis can lead to decreased UV-induced skin damage. Collectively, our study has suggested that UV-induced keratin 1 proteolysis may be a novel and valuable target for diagnosis, prevention and treatment of UV-induced skin damage.

pathology↗