Quantitative Analysis of the Expression of Human N-myristoyltransferase 1 (hNMT-1) in Cancers

Human N-myristoyltransferase 1 (hNMT-1) catalyzes the covalent attachment of myristic acid to N-terminal glycine residues (myristoylation) of numerous protein substrates. Overexpression of hNMT-1 in colorectal and gallbladder cancers makes it a potential biomarker and drug design target for such cancers. In this study, we investigated hNMT-1 expression during the progression of eight different human cancers using quantitative RT-PCR. The study results showed that hNMT-1 was up-regulated in breast, colon, lung and ovarian cancers but not kidney, liver, prostate and thyroid cancers. This suggests a role for hNMT-1 as a biomarker for detection of breast, colon, lung and ovarian cancers. This study also suggests the available hNMT-1 inhibitors may be potential therapeutic agents against breast and lung cancers through all disease stages, although their use would likely be limited to early stage colon and ovarian cancers.

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Synovial Fluid MicroRNA-210 as a Potential Biomarker for Early Prediction of Osteoarthritis

BioMed Research International ◽

10.1155/2019/7165406 ◽

2019 ◽

Vol 2019 ◽

pp. 1-4 ◽

Cited By ~ 6

Author(s):

Wen Xie ◽

Wei Su ◽

Hualing Xia ◽

Zhanchao Wang ◽

Chunxia Su ◽

...

Keyword(s):

Synovial Fluid ◽

Late Stage ◽

Early Stage ◽

Rt Pcr ◽

Vegf Expression ◽

Circulating Micrornas ◽

Protein Levels ◽

Diagnosis And Prognosis ◽

Potential Biomarker ◽

Inhibition Of Angiogenesis

Early detection and treatment are critical in the management of osteoarthritis (OA). OA is closely associated with angiogenesis and the inhibition of angiogenesis presents a novel therapeutic approach to reduce inflammation and pain in OA. Recent reports suggest that circulating microRNAs (miRNAs) have great potential as biomarkers for the diagnosis and prognosis in OA. In this study, we aimed to explore the clinical significance of miR-210 in synovial fluid samples from 10 healthy volunteers and 20 early-stage OA and 20 late-stage OA patients. miR-210 expression was assessed by real-time RT-PCR. VEGF protein levels were examined by ELISA. The results show that miR-210 is significantly upregulated in early-stage OA and late-stage OA patients compared with healthy individuals. Higher levels of VEGF are also found in OA compared with the control. Moreover, miR-210 levels are positively correlated with VEGF levels, suggesting that miR-210 might contribute to OA development through promoting VEGF expression and angiogenesis. In conclusion, upregulation of miR-210 in synovial fluid may occur in the early stage of OA and can be a useful biomarker for early diagnosis of OA.

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Comparison of clinical, laboratory and radiological features in confirmed and unconfirmed COVID-19 patients

Future Microbiology ◽

10.2217/fmb-2021-0162 ◽

2021 ◽

Author(s):

Serkan Surme ◽

Gulsah Tuncer ◽

Betul Copur ◽

Esra Zerdali ◽

Inci Yilmaz Nakir ◽

...

Keyword(s):

Clinical Laboratory ◽

Complete Blood Count ◽

Early Stage ◽

Close Contact ◽

Univariate Analysis ◽

Rt Pcr ◽

Radiological Findings ◽

Respiratory Illnesses ◽

Probable Case ◽

Study Results

Background: We aimed to compare the clinical, laboratory and radiological findings of confirmed COVID-19 and unconfirmed patients. Methods: This was a single-center, retrospective study. Results: Overall, 620 patients (338 confirmed COVID-19 and 282 unconfirmed) were included. Confirmed COVID‐19 patients had higher percentages of close contact with a confirmed or probable case. In univariate analysis, the presence of myalgia and dyspnea, decreased leukocyte, neutrophil and platelet counts were best predictors for SARS-CoV-2 RT-PCR positivity. Multivariate analyses revealed that only platelet count was an independent predictor for SARS-CoV-2 RT-PCR positivity. Conclusion: Routine complete blood count may be helpful for distinguishing COVID-19 from other respiratory illnesses at an early stage, while PCR testing is unique for the diagnosis of COVID-19.

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Plasma-derived exosomal miR-4732-5p is a promising noninvasive diagnostic biomarker for epithelial ovarian cancer

Journal of Ovarian Research ◽

10.1186/s13048-021-00814-z ◽

2021 ◽

Vol 14 (1) ◽

Author(s):

Jingjing Liu ◽

Jigeun Yoo ◽

Jung Yoon Ho ◽

Yuyeon Jung ◽

Sanha Lee ◽

...

Keyword(s):

Ovarian Cancer ◽

Epithelial Ovarian Cancer ◽

Healthy Subjects ◽

Early Stage ◽

Roc Curves ◽

Pcr Analysis ◽

Rt Pcr ◽

Potential Biomarker ◽

Exosomal Mirnas ◽

Exosomal Mirna

Abstract Background Exosomal miRNAs regulate gene expression and play important roles in several diseases. We used exosomal miRNA profiling to investigate diagnostic biomarkers of epithelial ovarian cancer (EOC). Methods In total, 55 individuals were enrolled, comprising healthy (n = 21) and EOC subjects (n = 34). Small mRNA (smRNA) sequencing and real-time PCR (RT-PCR) were performed to identify potential biomarkers. Receiver operating characteristic (ROC) curves were conducted to determine biomarker sensitivity and specificity. Results Using smRNA sequencing, we identified seven up-regulated (miR-4732-5p, miR-877-5p, miR-574-3p, let-7a-5p, let-7b-5p, let-7c-5p, and let-7f-5p) and two down-regulated miRNAs (miR-1273f and miR-342-3p) in EOC patients when compared with healthy subjects. Of these, miR-4732-5p and miR-1273f were the most up-regulated and down-regulated respectively, therefore they were selected for RT-PCR analysis. Plasma derived exosomal miR-4732-5p had an area under the ROC curve of 0.889, with 85.7% sensitivity and 82.4% specificity in distinguishing EOC patients from healthy subjects (p<0.0001) and could be a potential biomarker for monitoring the EOC progression from early stage to late stage (p = 0.018). Conclusions Plasma derived exosomal miR-4732-5p may be a promising candidate biomarker for diagnosing EOC.

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Genomic variations in plasma cell free DNA differentiate early stage lung cancers from normal controls

Lung Cancer ◽

10.1016/j.lungcan.2015.07.002 ◽

2015 ◽

Vol 90 (1) ◽

pp. 78-84 ◽

Cited By ~ 21

Author(s):

Shu Xia ◽

Chiang-Ching Huang ◽

Min Le ◽

Rachel Dittmar ◽

Meijun Du ◽

...

Keyword(s):

Plasma Cell ◽

Early Stage ◽

Cell Free Dna ◽

Lung Cancers ◽

Genomic Variations ◽

Free Dna ◽

Normal Controls

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Differences in physical symptoms between those with and without kidney disease: a comparative study across disease stages in a UK population

BMC Nephrology ◽

10.1186/s12882-021-02355-5 ◽

2021 ◽

Vol 22 (1) ◽

Author(s):

Thomas J. Wilkinson ◽

Daniel G. D. Nixon ◽

Jared Palmer ◽

Courtney J. Lightfoot ◽

Alice C. Smith

Keyword(s):

Kidney Disease ◽

Early Stage ◽

Symptom Burden ◽

Final Analysis ◽

Physical Symptoms ◽

Disease Trajectory ◽

High Prevalence ◽

Comparative Group ◽

The Difference ◽

Disease Stages

Abstract Background Those living with kidney disease (KD) report extensive symptom burden. However, research into how symptoms change across stages is limited. The aims of this study were to 1) describe symptom burden across disease trajectory, and 2) to explore whether symptom burden is unique to KD when compared to a non-KD population. Methods Participants aged > 18 years with a known diagnosis of KD (including haemodialysis (HD) and peritoneal dialysis (PD)) and with a kidney transplant) completed the Leicester Kidney Symptom Questionnaire (KSQ). A non-KD group was recruited as a comparative group. Multinominal logistic regression modelling was used to test the difference in likelihood of those with KD reporting each symptom. Results In total, 2279 participants were included in the final analysis (age 56.0 (17.8) years, 48% male). The main findings can be summarised as: 1) the number of symptoms increases as KD severity progresses; 2) those with early stage KD have a comparable number of symptoms to those without KD; 3) apart from those receiving PD, the most frequently reported symptom across every other group, including the non-KD group, was ‘feeling tired’; and 4) being female independently increased the likelihood of reporting more symptoms. Conclusions Our findings have important implications for patients with KD. We have shown that high symptom burden is prevalent across the spectrum of disease, and present novel data on symptoms experienced in those without KD. Symptoms requiring the most immediate attention given their high prevalence may include pain and fatigue. Trial registration The study was registered prospectively as ISRCTN11596292.

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Cognitive dysfunction in amyotrophic lateral sclerosis: can we predict it?

Neurological Sciences ◽

10.1007/s10072-021-05188-0 ◽

2021 ◽

Author(s):

Fabiola De Marchi ◽

◽

Claudia Carrarini ◽

Antonio De Martino ◽

Luca Diamanti ◽

...

Keyword(s):

Amyotrophic Lateral Sclerosis ◽

Time Course ◽

Neurodegenerative Disorder ◽

Early Stage ◽

Multisystem Disorder ◽

Behavioral Impairment ◽

Behavioral Impairments ◽

Als Patients ◽

Disease Stages ◽

Lateral Sclerosis

Abstract Background and aim Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder characterized by the degeneration of both upper and lower motoneurons in the brain and spinal cord leading to motor and extra-motor symptoms. Although traditionally considered a pure motor disease, recent evidences suggest that ALS is a multisystem disorder. Neuropsychological alterations, in fact, are observed in more than 50% of patients: while executive dysfunctions have been firstly identified, alterations in verbal fluency, behavior, and pragmatic and social cognition have also been described. Detecting and monitoring ALS cognitive and behavioral impairment even at early disease stages is likely to have staging and prognostic implications, and it may impact the enrollment in future clinical trials. During the last 10 years, humoral, radiological, neurophysiological, and genetic biomarkers have been reported in ALS, and some of them seem to potentially correlate to cognitive and behavioral impairment of patients. In this review, we sought to give an up-to-date state of the art of neuropsychological alterations in ALS: we will describe tests used to detect cognitive and behavioral impairment, and we will focus on promising non-invasive biomarkers to detect pre-clinical cognitive decline. Conclusions To date, the research on humoral, radiological, neurophysiological, and genetic correlates of neuropsychological alterations is at the early stage, and no conclusive longitudinal data have been published. Further and longitudinal studies on easily accessible and quantifiable biomarkers are needed to clarify the time course and the evolution of cognitive and behavioral impairments of ALS patients.

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Early alterations of neurovascular unit in the retina in mouse models of tauopathy

Acta Neuropathologica Communications ◽

10.1186/s40478-021-01149-y ◽

2021 ◽

Vol 9 (1) ◽

Author(s):

Fan Xia ◽

Yonju Ha ◽

Shuizhen Shi ◽

Yi Li ◽

Shengguo Li ◽

...

Keyword(s):

Transgenic Mice ◽

Mouse Models ◽

Molecular Mechanisms ◽

Early Stage ◽

Leukocyte Adhesion ◽

Neurovascular Unit ◽

Integrated Analysis ◽

Therapeutic Effects ◽

Retinal Ganglion ◽

Potential Biomarker

AbstractThe retina, as the only visually accessible tissue in the central nervous system, has attracted significant attention for evaluating it as a biomarker for neurodegenerative diseases. Yet, most of studies focus on characterizing the loss of retinal ganglion cells (RGCs) and degeneration of their axons. There is no integrated analysis addressing temporal alterations of different retinal cells in the neurovascular unit (NVU) in particular retinal vessels. Here we assessed NVU changes in two mouse models of tauopathy, P301S and P301L transgenic mice overexpressing the human tau mutated gene, and evaluated the therapeutic effects of a tau oligomer monoclonal antibody (TOMA). We found that retinal edema and breakdown of blood–retina barrier were observed at the very early stage of tauopathy. Leukocyte adhesion/infiltration, and microglial recruitment/activation were constantly increased in the retinal ganglion cell layer of tau transgenic mice at different ages, while Müller cell gliosis was only detected in relatively older tau mice. Concomitantly, the number and function of RGCs progressively decreased during aging although they were not considerably altered in the very early stage of tauopathy. Moreover, intrinsically photosensitive RGCs appeared more sensitive to tauopathy. Remarkably, TOMA treatment in young tau transgenic mice significantly attenuated vascular leakage, inflammation and RGC loss. Our data provide compelling evidence that abnormal tau accumulation can lead to pathology in the retinal NVU, and vascular alterations occur more manifest and earlier than neurodegeneration in the retina. Oligomeric tau-targeted immunotherapy has the potential to treat tau-induced retinopathies. These data suggest that retinal NVU may serve as a potential biomarker for diagnosis and staging of tauopathy as well as a platform to study the molecular mechanisms of neurodegeneration.

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Discovery and validation of novel protein markers in mucosa of portal hypertensive gastropathy

BMC Gastroenterology ◽

10.1186/s12876-021-01787-5 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ying Zhu ◽

Wen Xu ◽

Wei Hu ◽

Fang Wang ◽

Yan Zhou ◽

...

Keyword(s):

Portal Hypertension ◽

Gastric Mucosa ◽

Molecular Mechanisms ◽

Early Stage ◽

Trial Registration ◽

Portal Hypertensive Gastropathy ◽

Protein Markers ◽

Decompensated Liver Cirrhosis ◽

Potential Biomarker ◽

Normal Controls

Abstract Background Portal hypertension induced esophageal and gastric variceal bleeding is the main cause of death among patients of decompensated liver cirrhosis. Therefore, a standardized, biomarker-based test, to make an early-stage non-invasive risk assessment of portal hypertension, is highly desirable. However, no fit-for-purpose biomarkers have yet been identified. Methods We conducted a pilot study consisting of 5 portal hypertensive gastropathy (PHG) patients and 5 normal controls, sampling the gastric mucosa of normal controls and PHG patients before and after endoscopic cyanoacrylate injection, using label-free quantitative (LFQ) mass spectrometry, to identify potential biomarker candidates in gastric mucosa from PHG patients and normal controls. Then we further used parallel reaction monitoring (PRM) to verify the abundance of the targeted protein. Results LFQ analyses identified 423 significantly differentially expressed proteins. 17 proteins that significantly elevated in the gastric mucosa of PHG patients were further validated using PRM. Conclusions This is the first application of an LFQ-PRM workflow to identify and validate PHG–specific biomarkers in patient gastric mucosa samples. Our findings lay the foundation for comprehending the molecular mechanisms of PHG pathogenesis, and provide potential applications for useful biomarkers in early diagnosis and treatment. Trial registration and ethics approval: Trial registration was completed (ChiCTR2000029840) on February 25, 2020. Ethics Approvals were completed on July 17, 2017 (NYSZYYEC20180003) and February 15, 2020 (NYSZYYEC20200005).

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Sustained Systemic Levels of IL-6 Impinge Early Muscle Growth and Induce Muscle Atrophy and Wasting in Adulthood

Cells ◽

10.3390/cells10071816 ◽

2021 ◽

Vol 10 (7) ◽

pp. 1816

Author(s):

Laura Pelosi ◽

Maria Grazia Berardinelli ◽

Laura Forcina ◽

Francesca Ascenzi ◽

Emanuele Rizzuto ◽

...

Keyword(s):

Plasma Levels ◽

Muscle Wasting ◽

Inflammatory Diseases ◽

Early Stage ◽

Muscle Growth ◽

Postnatal Life ◽

Stunted Growth ◽

Skeletal Muscle Wasting ◽

Potential Biomarker ◽

Muscle Homeostasis

IL-6 is a pleiotropic cytokine that can exert different and opposite effects. The muscle-induced and transient expression of IL-6 can act in an autocrine or paracrine manner, stimulating anabolic pathways associated with muscle growth, myogenesis, and with regulation of energy metabolism. In contrast, under pathologic conditions, including muscular dystrophy, cancer associated cachexia, aging, chronic inflammatory diseases, and other pathologies, the plasma levels of IL-6 significantly increase, promoting muscle wasting. Nevertheless, the specific physio-pathological role exerted by IL-6 in the maintenance of differentiated phenotype remains to be addressed. The purpose of this study was to define the role of increased plasma levels of IL-6 on muscle homeostasis and the mechanisms contributing to muscle loss. Here, we reported that increased plasma levels of IL-6 promote alteration in muscle growth at early stage of postnatal life and induce muscle wasting by triggering a shift of the slow-twitch fibers toward a more sensitive fast fiber phenotype. These findings unveil a role for IL-6 as a potential biomarker of stunted growth and skeletal muscle wasting.

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