Search results for: neuroimaging biomarkers

Authors: Tarek Elnimr, Reda Morsy, Assem El Fert, Aziza Ismail

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Hepatitis is an inflammation of the liver. The condition can be self-limiting or can progress to fibrosis, cirrhosis or liver cancer. Disease caused by the hepatitis virus, the virus can cause hepatitis infection, ranging in severity from a mild illness lasting a few weeks to a serious, lifelong illness. A growing body of evidence indicates that many trace elements play important roles in a number of carcinogenic processes that proceed with various mechanisms. To examine the status of trace elements during the development of hepatic carcinoma, we determined the iron, copper, zinc and selenium levels in some biological samples of patients at different stages of viral hepatic disease. We observed significant changes in the iron, copper, zinc and selenium levels in the biological samples of patients hepatocellular carcinoma, relative to those of healthy controls. The mean hair, nail, RBC, serum and whole blood copper levels in patients with hepatitis virus were significantly higher than that of the control group. In contrast the mean iron, zinc, and selenium levels in patients having hepatitis virus were significantly lower than those of the control group. On the basis of this study, we identified the impact of natural supplements to improve the treatment of viral liver damage, using the level of some trace elements such as, iron, copper, zinc and selenium, which might serve as biomarkers for increases survival and reduces disease progression. Most of the elements revealed diverse and random distribution in the samples of the donor groups. The correlation study pointed out significant disparities in the mutual relationships among the trace elements in the patients and controls. Principal component analysis and cluster analysis of the element data manifested diverse apportionment of the selected elements in the scalp hair, nail and blood components of the patients compared with the healthy counterparts.

Keywords: hepatitis, hair, nail, blood components, trace element, nutrition therapy, multivariate analysis, correlation, ICP-MS

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Authors: Vitor Rafael Regiani, Carlos Henrique Viesi Do Nascimento Filho, Patricia Matos Biselli-Chicote, Claudia Aparecida Rainho, Luiz Sergio Raposo, José Victor Maniglia, Eny Maria Goloni-Bertollo, Erika Cristina Pavarino

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Promoter hypermethylation of tumor-related genes has been associated with prognosis in early-stage head-and-neck cancers, providing strong evidence that these hypermethylated genes are valuable biomarkers for prognostic evaluation. Hence, we selected the MGMT and RASSF1A genes to examine the methylation status in head and neck squamous cell carcinomas (HNSCC) samples matched with non-tumor tissues (tumor-surrounding tissues or peripheral blood samples). DNA methylation analysis was based on Methylation-Sensitive High Resolution Melting, and the methylation status was correlated with clinic-pathological characteristics of the patients. RASSF1A and MGMT promoter methylation was detected in 43.24% (16/37) and in 44.44% (16/36) of the tumors, respectively. RASSF1A and MGMT methylation was significantly more frequent in tumor tissue than non-tumor tissues, as well as, simultaneous methylation of RASSF1A and MGMT also was higher in tumor tissue than non-tumor tissues. In relation to anatomic site, larynx cancer presented significant methylation of MGMT gene compared to tumor-surrounding tissue. The frequency of RASSF1A and MGMT promoter methylated was higher in tumor tissues in relation to peripheral blood from the same patient. No association was found between methylation and the variables analyzed, including gender, age, smoking or alcohol drinking habits. Clinic-pathological characteristics also showed no association in the presence of methylation. The Kaplan–Meier's method showed no association of methylation and both disease-free and overall survival. In conclusion, the presence of epigenetic abnormalities in normal-appearing tissue corroborates the hypothesis of the ‘field cancerization', or it can reflect preneoplastic and/or preinvasive. Moreover, MGMT methylation may serve as an important laryngeal cancer biomarker because it showed significant difference between laryngeal cancer and surrounding tumor tissues.

Keywords: head and neck cancer, DNA methylation, MGMT promoter methylation, RASSF1A promoter methylation

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Authors: F. Alaa Ali, S. A. Sherein Abdelgayed, S. Osama. EL-Tawil, M. Adel Bakeer

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Tartrazine is an organic azo dyes food additive widely used in foods, drugs, and cosmetics. The present study aimed to investigate the toxic effects of tartrazine on kidneys and liver biomarkers in addition to the investigation of oxidative stress and change of histopathological structure of liver and kidneys in 30 male rats. Tartrazine was orally administrated daily at dose 200 mg/ kg bw (1/ 10 LD₅₀) for sixty days. Serum and tissue samples were collected at the end of the experiment to investigate the underlying mechanism of tartrazine through assessment oxidative stress (Glutathione (GSH), Superoxide dismutase (SOD) and malondialdehyde (MDA) and biochemical markers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), Total protein and Urea). Liver and kidneys tissue were collected and preserved in 10% formalin for histopathological examination. The obtained values were statistically analyzed by one way analysis of variance (ANOVA) followed by multiple comparison test. Biochemical analysis revealed that tartrazine induced significant increase in serum ALT, AST, total protein, urea level compared to control group. Tartrazine showed significant decrease in liver GSH and SOD where their values when compared to control group. Tartrazine induced increase in liver MDA compared to control group. Histopathology of the liver showed diffuse vacuolar degeneration in hepatic parenchyma, the portal area showed sever changes sever in hepatoportal blood vessels and in the bile ducts. The kidneys showed degenerated tubules at the cortex together with mononuclear leucocytes inflammatory cells infiltration. There is perivascular edema with inflammatory cell infiltration surrounding the congested and hyalinized vascular wall of blood vessel. The present study indicates that the subchronic effects of tartrazine have a toxic effect on the liver and kidneys together with induction of oxidative stress by formation of free radicals. Therefore, people should avoid the hazards of consuming tartrazine.

Keywords: albino rats, tartrazine, toxicity, pathology

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Authors: Peter W. Woodruff, Georgios Ponirakis, Reem Ibrahim, Amani Ahmed, Hoda Gad, Ioannis N. Petropoulos, Adnan Khan, Ahmed Elsotouhy, Surjith Vattoth, Mahmoud K. M. Alshawwaf, Mohamed Adil Shah Khoodoruth, Marwan Ramadan, Anjushri Bhagat, James Currie, Ziyad Mahfoud, Hanadi Al Hamad, Ahmed Own, Peter Haddad, Majid Alabdulla, Rayaz A. Malik

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Introduction:- We aimed to test the hypothesis that, using corneal confocal microscopy (a non-invasive method for assessing corneal nerve fibre integrity), patients with schizophrenia would show neuronal abnormalities compared with healthy participants. Schizophrenia is a neurodevelopmental and progressive neurodegenerative disease, for which there are no validated biomarkers. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging biomarker that can be used to detect neuronal abnormalities in neuropsychiatric syndromes. Methods:- Patients with schizophrenia (DSM-V criteria) without other causes of peripheral neuropathy and healthy controls underwent CCM, vibration perception threshold (VPT) and sudomotor function testing. The diagnostic accuracy of CCM in distinguishing patients from controls was assessed using the area under the curve (AUC) of the Receiver Operating Characterstics (ROC) curve. Findings:- Participants with schizophrenia (n=17) and controls (n=38) with comparable age (35.7±8.5 vs 35.6±12.2, P=0.96) were recruited. Patients with schizophrenia had significantly higher body weight (93.9±25.5 vs 77.1±10.1, P=0.02), lower Low Density Lipoproteins (2.6±1.0 vs 3.4±0.7, P=0.02), but comparable systolic and diastolic blood pressure, HbA1c, total cholesterol, triglycerides and High Density Lipoproteins were comparable with control participants. Patients with schizophrenia had significantly lower corneal nerve fiber density (CNFD, fibers/mm2) (23.5±7.8 vs 35.6±6.5, p<0.0001), branch density (CNBD, branches/mm2) (34.4±26.9 vs 98.1±30.6, p<0.0001), and fiber length (CNFL, mm/mm2) (14.3±4.7 vs 24.2±3.9, p<0.0001) but no difference in VPT (6.1±3.1 vs 4.5±2.8, p=0.12) and electrochemical skin conductance (61.0±24.0 vs 68.9±12.3, p=0.23) compared with controls. The diagnostic accuracy of CNFD, CNBD and CNFL to distinguish patients with schizophrenia from healthy controls were, according to the AUC, (95% CI): 87.0% (76.8-98.2), 93.2% (84.2-102.3), 93.2% (84.4-102.1), respectively. Conclusion:- In conclusion, CCM can be used to help identify neuronal changes and has a high diagnostic accuracy to distinguish subjects with schizophrenia from healthy controls.

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Authors: Rayhana Begum, Manju Sharma

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Careya arborea Roxb. belongs to the Lecythidaceae family, is traditionally used in tumors, anthelmintic, bronchitis, epileptic fits, astringents, inflammation, an antidote to snake-venom, skin disease, diarrhea, dysentery with bloody stools, dyspepsia, ulcer, toothache, and ear pain. The present study was focused on investigating the anti-arthritic effect of coumaroyl lupendioic acid, a new lupane-type triterpene from Careya arborea stem bark in the chronic inflammatory model and further assessing its possible mechanism on the modulation of inflammatory biomarkers. Arthritis was induced by injecting 0.1 ml of Complete Freund’s Adjuvant (5 mg/ml of heat killed Mycobacterium tuberculosis) into the subplantar region of the left hind paw. Treatment with coumaroyl lupendioic acid (10 and 20 mg/kg, p.o.) and reference drugs (indomethacin and dexamethasone at the dose of 5 mg/kg, p.o.) were started on the day of induction and continued up to 28 days. The progression of arthritis was evaluated by measuring paw volume, tibio tarsal joint diameters, and arthritic index. The effect of coumaroyl lupendioic acid (CLA) on the production PGE₂, NO, MPO, NF-κB, TNF-α, IL-1β, and IL-6 on serum level as well as inflamed paw tissue were also assessed. In addition, ankle joints and spleen were collected and prepared for histological examination. CLA in inflamed rats resulted in significant amelioration of paw edema, tibio-tarsal joint swelling and arthritic score as compared to CFA control group. The results indicated that CLA treated groups markedly decreased the levels of inflammatory mediators (PGE₂, NO, MPO and NF-κB levels) and down-regulated the production of pro-inflammatory cytokines (TNF-α, IL-1β, and IL-6) in paw tissue homogenates as well as in serum. However, the more pronounced effect was observed in the inflamed paw tissue homogenates. CLA also revealed a protective effect to the tibio-tarsal joint cartilage and spleen. These results suggest that coumaroyl lupendioic acid inhibits inflammation may be through the suppression of the cascade of proinflammatory mediators via the down-regulation of NF-ҡB.

Keywords: complete Freund’s adjuvant , Coumaroyl lupendioic acid, pro-inflammatory cytokines, prostaglandin E2

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Authors: Maha Z. Rizk, Sami A. Fattah, Heba M. Darwish, Sanaa A. Ali, Mai O. Kadry

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Although it is known that nano-TiO2 and other nanoparticles can induce liver toxicity, the mechanisms and the molecular pathogenesis are still unclear. The present study investigated some biochemical indices of nano-sized Titanium dioxide (TiO2 NPS) toxicity in mice liver and the ameliorative efficacy of individual and combined doses of idebenone, carnosine and vitamin E. Nano-anatase TiO2 (21 nm) was administered as a total oral dose of 2.2 gm/Kg daily for 2 weeks followed by the afore-mentioned antioxidants daily either individually or in combination for 1month. TiO2-NPS induced a significant elevation in serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST) and hepatic oxidative stress biomarkers [lipid peroxides (LP), and nitric oxide levels (NOX), while it significantly reduced glutathione reductase (GR), reduced glutathione (GSH) and glutathione peroxidase(GPX) levels. Moreover the quantitative RT-PCR analysis showed that nano-anatase TiO2 can significantly alter the mRNA and protein expressions of the fibrotic factors TGF-B1, VEGFand Smad-2. Histopathological examination of hepatic tissue reinforced the previous biochemical results. Our results also implied that inflammatory responses and liver injury may be involved in nano-anatase TiO2-induced liver toxicity Tumor necrosis factor-α (TNF-α) and Interleukin -6 (IL-6) and increased the percent of DNA damage which was assessed by COMET assay in addition to the apoptotic marker Caspase-3. Moreover mRNA gene expression observed by RT-PCR showed a significant overexpression in nuclear factor relation -2 (Nrf2), nuclear factor kappa beta (NF-Kβ) and the apoptotic factor (bax), and a significant down regulation in the antiapoptotic factor (bcl2) level. In conclusion idebenone, carnosine and vitamin E ameliorated the deviated previously mentioned parameters with variable degrees with the most pronounced role in alleviating the hazardous effect of TiO2 NPS toxicity following the combination regimen.

Keywords: Nano-anatase TiO2, TGF-B1, SMAD-2

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Authors: Maryam Fallahpoor, Biswajeet Pradhan

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Background: Artificial intelligence (AI) serves as a valuable tool in mitigating the scarcity of human resources required for the evaluation and categorization of vast quantities of medical imaging data. When AI operates with optimal precision, it minimizes the demand for human interpretations and, thereby, reduces the burden on radiologists. Among various AI approaches, deep learning (DL) stands out as it obviates the need for feature extraction, a process that can impede classification, especially with intricate datasets. The advent of DL models has ushered in a new era in medical imaging, particularly in the context of COVID-19 detection. Traditional 2D imaging techniques exhibit limitations when applied to volumetric data, such as Computed Tomography (CT) scans. Medical images predominantly exist in one of two formats: neuroimaging informatics technology initiative (NIfTI) and digital imaging and communications in medicine (DICOM). Purpose: This study aims to employ DL for the classification of COVID-19-infected pulmonary patients and normal cases based on 3D CT scans while investigating the impact of image format. Material and Methods: The dataset used for model training and testing consisted of 1245 patients from IranMehr Hospital. All scans shared a matrix size of 512 × 512, although they exhibited varying slice numbers. Consequently, after loading the DICOM CT scans, image resampling and interpolation were performed to standardize the slice count. All images underwent cropping and resampling, resulting in uniform dimensions of 128 × 128 × 60. Resolution uniformity was achieved through resampling to 1 mm × 1 mm × 1 mm, and image intensities were confined to the range of (−1000, 400) Hounsfield units (HU). For classification purposes, positive pulmonary COVID-19 involvement was designated as 1, while normal images were assigned a value of 0. Subsequently, a U-net-based lung segmentation module was applied to obtain 3D segmented lung regions. The pre-processing stage included normalization, zero-centering, and shuffling. Four distinct 3D CNN models (ResNet152, ResNet50, DensNet169, and DensNet201) were employed in this study. Results: The findings revealed that the segmentation technique yielded superior results for DICOM images, which could be attributed to the potential loss of information during the conversion of original DICOM images to NIFTI format. Notably, ResNet152 and ResNet50 exhibited the highest accuracy at 90.0%, and the same models achieved the best F1 score at 87%. ResNet152 also secured the highest Area under the Curve (AUC) at 0.932. Regarding sensitivity and specificity, DensNet201 achieved the highest values at 93% and 96%, respectively. Conclusion: This study underscores the capacity of deep learning to classify COVID-19 pulmonary involvement using real 3D hospital data. The results underscore the significance of employing DICOM format 3D CT images alongside appropriate pre-processing techniques when training DL models for COVID-19 detection. This approach enhances the accuracy and reliability of diagnostic systems for COVID-19 detection.

Keywords: deep learning, COVID-19 detection, NIFTI format, DICOM format

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Authors: Jagruti Barot

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The textile industry plays a major role in the economy of India and on the other side of the coin it is the major source for water pollution. As azo dyes is the largest dye class they are extensively used in many fields such as textile industry, leather tanning industry, paper production, food, colour photography, pharmaceuticals and medicine, cosmetic, hair colourings, wood staining, agricultural, biological and chemical research etc. In addition to these, they can have acute and/or chronic effects on organisms depending on their concentration and length of exposure when they discharged as effluent in the environment. The aim of this study was to assess the genotoxic and histotoxic potentials of environmentally relevant concentrations of RR 120 on Catla catla, important edible freshwater fingerlings. For this, healthy Catla catla fingerlings were procured from the Government Fish Farm and acclimatized in 100 L capacity and continuously aerated glass aquarium in laboratory for 15 days. According to APHA some physic-chemical parameters were measured and maintained such as temperature, pH, dissolve oxygen, alkalinity, total hardness. Water along with excreta had been changed every 24 hrs. All fingerlings were fed artificial food palates once a day @ body weight. After 15 days fingerlings were grouped in 5 (10 in each) and exposed to various concentrations of RR 120 (Control, 10, 20, 30 and 40 mg/L) and samples (peripheral blood and gills, kidney) were collected and analyzed at 96 hrs. of interval. All results were compared with the control. Micronuclei (MN), nuclear buds (NB), fragmented-apoptotic (FA) and bi-nucleated (BN) cells in blood cells and in tissues (gills and kidney cells) were observed. Prominent histopathological alterations were noticed in gills such as aneurism, hyperplasia, degenerated central axis, lifting of gill epithelium, curved secondary gill lamellae etc. Similarly kidney showed some detrimental changes like shrunken glomeruli with increased periglomerular space, degenerated renal tubules etc. Both haematological and histopathological changes clearly reveal the toxic potential of RR 120. This work concludes that water pollution assessment can be done by these two biomarkers which provide baseline to the further chromosomal or molecular work.

Keywords: micronuclei, genotoxicity, RR 120, Catla catla

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Authors: Igor Jerkovic

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Owing to the attractive sensory properties and low odour thresholds, norisoprenoids (degraded carotenoid-like structures with 3,5,5-trimethylcyclohex-2-enoic unit) have been identified as aroma contributors in a number of different matrices. C₁₃-Norisoprenoids have been found among volatile organic compounds of various honey types as well as C₉//C₁₀-norisoprenoids or C₁₄/C₁₅-norisoprenoids. Besides degradation of abscisic acid (which produces, e.g., dehydrovomifoliol, vomifoliol, others), the cleavage of the C(9)=C(10) bond of other carotenoid precursors directly generates nonspecific C₁₃-norisoprenoids such as trans-β-damascenone, 3-hydroxy-trans-β-damascone, 3-oxo-α-ionol, 3-oxo-α-ionone, β-ionone found in various honey types. β-Damascenone and β-ionone smelling like honey, exhibit the lowest odour threshold values of all C₁₃-norisoprenoids. The presentation is targeted on two uncommon C₁₃-norisoprenoids in the honey flavor that could be used as specific or nonspecific chemical markers of the botanical origin. Namely, after screening of different honey types, the focus was directed on Centaruea cyanus L. and Allium ursinum L. honey. The samples were extracted by headspace solid-phase microextraction (HS-SPME) and ultrasonic solvent extraction (USE) and the extracts were analysed by gas chromatography and mass spectrometry (GC-MS). SPME fiber with divinylbenzene/carboxen/polydimethylsiloxane (DVB/CAR/PDMS) coating was applied for the research of C. cyanus honey headspace and predominant identified compound was 3,4-dihydro-3-oxoedulan (2,5,5,8a-tetramethyl-2,3,5,6,8,8a-hexahydro-7H-chromen-7-one also known as 2,3,5,6,8,8a-hexahydro-2,5,5,8a-tetramethyl-7H-1-benzo-pyran-7-one). The oxoedulan structure contains epoxide and it is more volatile in comparison with its hydroxylated precursors. This compound has not been found in other honey types and can be considered specific for C. cyanus honey. The dichloromethane extract of A. ursinum honey contained abundant (E)-4-(r-1',t-2',c-4'-trihydroxy-3',6',6'-trimethylcyclohexyl)-but-3-en-2-one that was previously isolated as dominant substance from the ether extracts of New Zealand thyme honey. Although a wide variety of degraded carotenoid-like substances have been identified from different honey types, this appears to be rare situation where 3,4-dihydro-3-oxoedulan and (E)-4-(r-1',t-2',c-4'-trihydroxy-3',6',6'-trimethylcyclohexyl)-but-3-en-2-one have been found that is of great importance for chemical fingerprinting and identification of the chemical biomarkers that can complement the pollen analysis as the major method for the honey classification.

Keywords: 3, 4-dihydro-3-oxoedulan, (E)-4-(r-1', t-2', c-4'-trihydroxy-3', 6', 6'-trimethylcyclohexyl)-but-3-en-2-one, honey flavour, C₁₃-norisoprenoids

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Authors: G. Amariei, K. Boltes, R. Rosal, P. Leton

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Wastewater treatment plants (WWTPs) are supposed to hold an important place in the reduction of emerging contaminants, but provide an environment that has potential for the development and/or spread of adaptation, as bacteria are continuously mixed with contaminants at sub-inhibitory concentrations. Reviewing the literature, there are little data available regarding the use of adapted bacteria forming activated sludge community for toxicity assessment, and only individual validations have been performed. Therefore, the aim of this work was to study the toxicity of Triclosan (TCS) and Ibuprofen (IBU), individually and in binary combination, on adapted activated sludge (AS). For this purpose a battery of biomarkers were assessed, involving oxidative stress and cytotoxicity responses: glutation-S-transferase (GST), catalase (CAT) and viable cells with FDA. In addition, we compared the toxic effects on adapted bacteria with unadapted bacteria, from a previous research. Adapted AS comes from three continuous-flow AS laboratory systems; two systems received IBU and TCS, individually; while the other received the binary combination, for 14 days. After adaptation, each bacterial culture condition was exposure to IBU, TCS and the combination, at 12 h. The concentration of IBU and TCS ranged 0.5-4mg/L and 0.012-0.1 mg/L, respectively. Batch toxicity experiments were performed using Oxygraph system (Hansatech), for determining the activity of CAT enzyme based on the quantification of oxygen production rate. Fluorimetric technique was applied as well, using a Fluoroskan Ascent Fl (Thermo) for determining the activity of GST enzyme, using monochlorobimane-GSH as substrate, and to the estimation of viable cell of the sludge, by fluorescence staining using Fluorescein Diacetate (FDA). For IBU adapted sludge, CAT activity it was increased at low concentration of IBU, TCS and mixture. However, increasing the concentration the behavior was different: while IBU tends to stabilize the CAT activity, TCS and the mixture decreased this one. GST activity was significantly increased by TCS and mixture. For IBU, no variations it was observed. For TCS adapted sludge, no significant variations on CAT activity it was observed. GST activity it was significant decreased for all contaminants. For mixture adapted sludge the behaviour of CAT activity it was similar to IBU adapted sludge. GST activity it was decreased at all concentration of IBU. While the presence of TCS and mixture, respectively, increased the GST activity. These findings were consistent with the viability cells evaluation, which clearly showed a variation of sludge viability. Our results suggest that, compared with unadapted bacteria, the adapted bacteria conditions plays a relevant role in the toxicity behaviour towards activated sludge communities.

Keywords: adapted sludge community, mixture, PPCPs, toxicity

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Authors: Pavel Damborsky, Martina Zamorova, Jaroslav Katrlik

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Prostate cancer is annually the most common newly diagnosed cancer among men. An extensive number of evidence suggests that traditional serum Prostate-specific antigen (PSA) assay still suffers from a lack of sufficient specificity and sensitivity resulting in vast over-diagnosis and overtreatment. Thus, the early-stage detection of prostate cancer (PCa) plays undisputedly a critical role for successful treatment and improved quality of life. Over the last decade, particular altered glycans have been described that are associated with a range of chronic diseases, including cancer and inflammation. These glycans differences enable a distinction to be made between physiological and pathological state and suggest a valuable biosensing tool for diagnosis and follow-up purposes. Aberrant glycosylation is one of the major characteristics of disease progression. Consequently, the aim of this study was to develop a more reliable tool for early-stage PCa diagnosis employing lectins as glyco-recognition elements. Biosensor and biochip technology putting to use lectin-based glyco-profiling is one of the most promising strategies aimed at providing fast and efficient analysis of glycoproteins. The proof-of-concept experiments based on sandwich assay employing anti-PSA antibody and an aptamer as a capture molecules followed by lectin glycoprofiling were performed. We present a lectin-based biosensing assay for glycoprofiling of serum biomarker PSA using different biosensor and biochip platforms such as label-free surface plasmon resonance (SPR) and microarray with fluorescent label. The results suggest significant differences in interaction of particular lectins with PSA. The antibody-based assay is frequently associated with the sensitivity, reproducibility, and cross-reactivity issues. Aptamers provide remarkable advantages over antibodies due to the nucleic acid origin, stability and no glycosylation. All these data are further step for construction of highly selective, sensitive and reliable sensors for early-stage diagnosis. The experimental set-up also holds promise for the development of comparable assays with other glycosylated disease biomarkers.

Keywords: biomarker, glycosylation, lectin, prostate cancer

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Authors: Svetlana Guryeva, Inna Kornienko, Andrey Usanov, Dmitry Usanov, Elena Petersen

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Every day cells in our organism are exposed to various factors: chemical agents, reactive oxygen species, ionizing radiation, and others. These factors can cause damage to DNA, cellular membrane, intracellular compartments, and proteins. The fate of cells depends on the exposure intensity and duration. The prolonged and intense exposure causes the irreversible damage accumulation, which triggers the permanent cell cycle arrest (cellular senescence) or cell death programs. In the case of low dose of impacts, it can lead to cell renovation and to cell functional state improvement. Therefore, it is a pivotal question to investigate the factors and doses that result in described positive effects. In order to estimate the influence of different agents, the proliferation index and levels of cell death markers (annexin V/propidium iodide), senescence-associated β-galactosidase, and lipofuscin were measured. The experiments were conducted on primary human fibroblasts of the 8th passage. According to the levels of mentioned markers, these cells were defined as senescent cells. The effect of low-frequency magnetic field was investigated. Different modes of magnetic field exposure were tested. The physical agents were compared with chemical agents: metformin (10 mM) and taurine (0.8 mM and 1.6 mM). Cells were incubating with chemicals for 5 days. The highest decrease in the level of senescence-associated β-galactosidase (21%) and lipofuscin (17%) was observed in the primary senescent fibroblasts after 5 days after double treatments with 48 h intervals with low-frequency magnetic field. There were no significant changes in the proliferation index after magnetic field application. The cytotoxic effect of magnetic field was not observed. The chemical agent taurine (1.6 mM) decreased the level of senescence-associated β-galactosidase (23%) and lipofuscin (22%). Metformin improved the activity of senescence-associated β-galactosidase on 15% and the level of lipofuscin on 19% in this experiment. According to these results, the effect of double treatment with 48 h interval with low-frequency magnetic field and the effect of taurine (1.6 mM) were comparable to the effect of metformin, for which anti-aging properties are proved. In conclusion, this study can become the first step towards creation of the standardized system for the investigation of different effects on senescent cells.

Keywords: biomarkers, magnetic field, metformin, primary fibroblasts, senescence, taurine

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Authors: Wilfred A. Abiaa, Chibundu N. Ezekiel, Benedikt Warth, Michael Sulyok, Paul C. Turner, Rudolf Krska, Paul F. Moundipa

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Mycotoxins are a wide range of toxic secondary metabolites of fungi that contaminate various food commodities worldwide especially in sub-Saharan Africa (SSA). Such contamination seriously compromises food safety and quality posing a serious problem for human health as well as to trade and the economy. Their concentrations depend on various factors, such as the commodity itself, climatic conditions, storage conditions, seasonal variances, and processing methods. When humans consume foods contaminated by mycotoxins, they exert toxic effects to their health through various modes of actions. Rural populations in sub-Saharan Africa, are exposed to dietary mycotoxins, but it is supposed that exposure levels and health risks associated with mycotoxins between SSA countries may vary. Dietary exposures and health risk assessment studies have been limited by lack of equipment for the proper assessment of the associated health implications on consumer populations when they eat contaminated agricultural products. As such, mycotoxin research is premature in several SSA nations with product evaluation for mycotoxin loads below/above legislative limits being inadequate. Few nations have health risk assessment reports mainly based on direct quantification of the toxins in foods ('external exposure') and linking food levels with data from food frequency questionnaires. Nonetheless, the assessment of the exposure and health risk to mycotoxins requires more than the traditional approaches. Only a fraction of the mycotoxins in contaminated foods reaches the blood stream and exert toxicity ('internal exposure'). Also, internal exposure is usually smaller than external exposure thus dependence on external exposure alone may induce confounders in risk assessment. Some studies from SSA earlier focused on biomarker analysis mainly on aflatoxins while a few recent studies have concentrated on the multi-biomarker analysis of exposures in urine providing probable associations between observed disease occurrences and dietary mycotoxins levels. As a result, new techniques that could assess the levels of exposures directly in body tissue or fluid, and possibly link them to the disease state of individuals became urgent.

Keywords: mycotoxins, biomarkers, exposure assessment, health risk assessment, sub-Saharan Africa

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Authors: Maria Lopez-Ibarra, Ana Velazquez-Wong, Lucelli Yañez-Gutierrez, Maria Araujo-Solis, Fabio Salamanca-Gomez, Alfonso Mendez-Tenorio, Haydeé Rosas-Vargas

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Congenital heart diseases (CHD) are the most common congenital abnormalities. These conditions can occur as both an element of distinct chromosomal malformation syndromes or as non-syndromic forms. Their etiology is not fully understood. Genetic variants such copy number variants have been associated with CHD. The aim of our study was to analyze these genomic variants in peripheral blood from Mexican children diagnosed with non-syndromic CHD. We included 16 children with atrial and ventricular septal defects and 5 healthy subjects without heart malformations as controls. To exclude the most common heart disease-associated syndrome alteration, we performed a fluorescence in situ hybridization test to identify the 22q11.2, responsible for congenital heart abnormalities associated with Di-George Syndrome. Then, a microarray based comparative genomic hybridization was used to identify global copy number variants. The identification of copy number variants resulted from the comparison and analysis between our results and data from main genetic variation databases. We identified copy number variants gain in three chromosomes regions from pediatric patients, 4q13.2 (31.25%), 9q34.3 (25%) and 20q13.33 (50%), where several genes associated with cellular, biosynthetic, and metabolic processes are located, UGT2B15, UGT2B17, SNAPC4, SDCCAG3, PMPCA, INPP6E, C9orf163, NOTCH1, C20orf166, and SLCO4A1. In addition, after a hierarchical cluster analysis based on the fluorescence intensity ratios from the comparative genomic hybridization, two congenital heart disease groups were generated corresponding to children with atrial or ventricular septal defects. Further analysis with a larger sample size is needed to corroborate these copy number variants as possible biomarkers to differentiate between heart abnormalities. Interestingly, the 20q13.33 gain was present in 50% of children with these CHD which could suggest that alterations in both coding and non-coding elements within this chromosomal region may play an important role in distinct heart conditions.

Keywords: aCGH, bioinformatics, congenital heart diseases, copy number variants, fluorescence in situ hybridization

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Authors: Shveta Bathla, Preeti Rawat, Sudarshan Kumar, Rubina Baithalu, Jogender Singh Rana, Tushar Kumar Mohanty, Ashok Kumar Mohanty

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Pregnancy is a complex process which includes series of events such as fertilization, formation of blastocyst, implantation of embryo, placental formation and development of fetus. The success of these events depends on various interactions which are synchronized by endocrine interaction between a receptive dam and competent embryo. These interactions lead to change in expression of hormones and proteins. But till date no protein biomarker is available which can be used to detect successful completion of these events. We employed quantitative proteomics approach to develop putative serological biomarker which has diagnostic applicability for early detection of pregnancy in cows. For this study, sera were collected from control (non-pregnant, n=6) and pregnant animals on successive days of pregnancy (7, 19, 45, n=6). The sera were subjected to depletion for removal of albumin using Norgen depletion kit. The tryptic peptides were labeled with iTRAQ. The peptides were pooled and fractionated using bRPLC over 80 min gradient. Then 12 fractions were injected to nLC for identification and quantitation in DDA mode using ESI. Identification using Mascot search revealed 2056 proteins out of which 352 proteins were differentially expressed. Twenty proteins were upregulated and twelve proteins were down-regulated with fold change > 1.5 and < 0.6 respectively (p < 0.05). The gene ontology studies of DEPs using Panther software revealed that majority of proteins are actively involved in catalytic activities, binding and enzyme regulatory activities. The DEP'S such as NF2, MAPK, GRIPI, UGT1A1, PARP, CD68 were further subjected to pathway analysis using KEGG and Cytoscape plugin Cluego that showed involvement of proteins in successful implantation, maintenance of pluripotency, regulation of luteal function, differentiation of endometrial macrophages, protection from oxidative stress and developmental pathways such as Hippo. Further efforts are continuing for targeted proteomics, western blot to validate potential biomarkers and development of diagnostic kit for early pregnancy diagnosis in cows.

Keywords: bRPLC, Cluego, ESI, iTRAQ, KEGG, Panther

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Authors: Sayani Chatterjee, Kusum Lata Pangtey, Sarita Singh, Harvir Singh

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Biodegradation leads to a systematic alteration of the chemical and physical properties of crude oil showing sequential depletion of n-alkane, cycloalkanes, aromatic which increases its specific gravity, viscosity and the abundance of heteroatom-containing compounds. The biodegradation leads to a change in the molecular fingerprints and geochemical parameters of degraded oils, thus make source and maturity identification inconclusive or ambiguous. Asphaltene is equivalent to the most labile part of the respective kerogen and generally has high molecular weight. Its complex chemical structure with substantial microporous units makes it suitable to occlude the hydrocarbon expelled from the source. The occluded molecules are well preserved by the macromolecular structure and thus prevented from secondary alterations. They retain primary organic geochemical information over the geological time. The present study involves the extraction of this occluded hydrocarbon from the asphaltene cage through mild oxidative degradation using mild oxidative reagents like Hydrogen Peroxide (H₂O₂) and Acetic Acid (CH₃COOH) on purified asphaltene of the biodegraded oils of Mansa, Lanwa and Santhal fields in Cambay Basin. The study of these extracted occluded hydrocarbons was carried out for establishing oil to oil and oil to source correlation in the Mehsana block of Cambay Basin. The n-alkane and biomarker analysis through GC and GC-MS of these occluded hydrocarbons show similar biomarker imprint as the normal oil in the area and hence correlatable with them. The abundance of C29 steranes, presence of Oleanane, Gammacerane and 4-Methyl sterane depicts that the oils are derived from terrestrial organic matter deposited in the stratified saline water column in the marine environment with moderate maturity (VRc 0.6-0.8). The oil source correlation study suggests that the oils are derived from Jotana-Warosan Low area. The developed geochemical technique to extract the occluded hydrocarbon has effectively resolved the ambiguity that resulted from the inconclusive fingerprint of the biodegraded oil and the method can be also applied in other biodegraded oils as well.

Keywords: asphaltene, biomarkers, correlation, mild oxidation, occluded hydrocarbon

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Authors: Yelin Zhao, Xinxiu Li, Martin Smelik, Oleg Sysoev, Firoj Mahmud, Dina Mansour Aly, Mikael Benson

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Background: Early diagnosis of pancreatic cancer is clinically challenging due to vague, or no symptoms, and lack of biomarkers. Polygenic risk score (PRS) scores may provide a valuable tool to assess increased or decreased risk of PC. This study aimed to develop such PRS by filtering genetic variants identified by GWAS using transcriptional programs identified by single-cell RNA sequencing (scRNA-seq). Methods: ScRNA-seq data from 24 pancreatic ductal adenocarcinoma (PDAC) tumor samples and 11 normal pancreases were analyzed to identify differentially expressed genes (DEGs) in in tumor and microenvironment cell types compared to healthy tissues. Pathway analysis showed that the DEGs were enriched for hundreds of significant pathways. These were clustered into 40 “programs” based on gene similarity, using the Jaccard index. Published genetic variants associated with PDAC were mapped to each program to generate program PRSs (pPRSs). These pPRSs, along with five previously published PRSs (PGS000083, PGS000725, PGS000663, PGS000159, and PGS002264), were evaluated in a European-origin population from the UK Biobank, consisting of 1,310 PDAC participants and 407,473 non-pancreatic cancer participants. Stepwise Cox regression analysis was performed to determine associations between pPRSs with the development of PC, with adjustments of sex and principal components of genetic ancestry. Results: The PDAC genetic variants were mapped to 23 programs and were used to generate pPRSs for these programs. Four distinct pPRSs (P1, P6, P11, and P16) and two published PRSs (PGS000663 and PGS002264) were significantly associated with an increased risk of developing PC. Among these, P6 exhibited the greatest hazard ratio (adjusted HR[95% CI] = 1.67[1.14-2.45], p = 0.008). In contrast, P10 and P4 were associated with lower risk of developing PC (adjusted HR[95% CI] = 0.58[0.42-0.81], p = 0.001, and adjusted HR[95% CI] = 0.75[0.59-0.96], p = 0.019). By comparison, two of the five published PRS exhibited an association with PDAC onset with HR (PGS000663: adjusted HR[95% CI] = 1.24[1.14-1.35], p < 0.001 and PGS002264: adjusted HR[95% CI] = 1.14[1.07-1.22], p < 0.001). Conclusion: Compared to published PRSs, scRNA-seq-based pPRSs may be used not only to assess increased but also decreased risk of PDAC.

Keywords: cox regression, pancreatic cancer, polygenic risk score, scRNA-seq, UK biobank

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Authors: Mohammadjavad Sotoudeheian

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COVID-19, which began in December 2019, uses the angiotensin-converting enzyme 2 (ACE2) receptor to enter and spread through the cells. ACE2 mRNA is present in almost every organ, including nasopharynx, lung, as well as the brain. Ports of entry of SARS-CoV-2 into the central nervous system (CNS) may include arterial circulation, while viremia is remarkable. However, it is imperious to develop neurological symptoms evaluation CSF analysis in patients with COVID-19, but theoretically, ACE2 receptors are expressed in cerebellar cells and may be a target for SARS-CoV-2 infection in the brain. Recent evidence agrees that SARS-CoV-2 can impact the brain through direct and indirect injury. Two biomarkers for CNS injury, glial fibrillary acidic protein (GFAP) and neurofilament light chain (NFL) detected in the plasma of patients with COVID-19. NFL, an axonal protein expressed in neurons, is related to axonal neurodegeneration, and GFAP is over-expressed in CNS inflammation. GFAP cytoplasmic accumulation causes Schwan cells to misfunction, so affects myelin generation, reduces neuroskeletal support over NfLs during CNS inflammation, and leads to axonal degeneration. Interleukin-6 (IL-6), which extensively over-express due to interleukin storm during COVID-19 inflammation, regulates gene expression, as well as GFAP through STAT molecular pathway. IL-6 also impresses the phosphoinositide 3-kinase (PI3K)/STAT/smads pathway. The PI3K/ protein kinase B (Akt) pathway is the main modulator upstream of the mammalian target of rapamycin (mTOR), and alterations in this pathway are common in neurodegenerative diseases. Most neurodegenerative diseases show a disruption of autophagic function and display an abnormal increase in protein aggregation that promotes cellular death. Therefore, induction of autophagy has been recommended as a rational approach to help neurons clear abnormal protein aggregates and survive. The mTOR is a major regulator of the autophagic process and is regulated by cellular stressors. The mTORC1 pathway and mTORC2, as complementary and important elements in mTORC1 signaling, have become relevant in the regulation of the autophagic process and cellular survival through the extracellular signal-regulated kinase (ERK) pathway.

Keywords: mTORC1, COVID-19, PI3K, autophagy, neurodegeneration

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Authors: Ieva Bruzauskaite, Jovile Raudoniute, Karina Poliakovaite, Danguole Zabulyte, Daiva Bironaite, Ruta Aldonyte

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Introduction: Air pollution is a growing global problem which has been shown to be responsible for various adverse health outcomes. Immunotoxicity, such as dysregulated inflammation, has been proposed as one of the main mechanisms in air pollution-associated diseases. Chronic obstructive pulmonary disease (COPD) is among major morbidity and mortality causes worldwide and is characterized by persistent airflow limitation caused by the small airways disease (obstructive bronchiolitis) and irreversible parenchymal destruction (emphysema). Exact pathways explaining the air pollution induced and mediated disease states are still not clear. However, modern societies understand dangers of polluted air, seek to mitigate such effects and are in need for reliable biomarkers of air pollution. We hypothesise that post-translational modifications of structural proteins, e.g. citrullination, might be a good candidate biomarker. Thus, we have designed this study, where mice were exposed to diesel exhaust and the ongoing protein modifications and inflammation in lungs and other tissues were assessed. Materials And Methods: To assess the effects of diesel exhaust a in vivo study was designed. Mice (n=10) were subjected to everyday 2-hour exposure to diesel exhaust for 14 days. Control mice were treated the same way without diesel exhaust. The effects within lung and other tissues were assessed by immunohistochemistry of formalin-fixed and paraffin-embedded tissues. Levels of inflammation and citrullination related markers were investigated. Levels of parenchymal damage were also measured. Results: In vivo study corroborates our own data from in vitro and reveals diesel exhaust initiated inflammatory shift and modulation of lung peptidyl arginine deiminase 4 (PAD4), citrullination associated enzyme, levels. In addition, high levels of citrulline were observed in exposed lung tissue sections co-localising with increased parenchymal destruction. Conclusions: Subacute exposure to diesel exhaust renders mice lungs inflammatory and modifies certain structural proteins. Such structural changes of proteins may pave a pathways to lost/gain function of affected molecules and also propagate autoimmune processes within the lung and systemically.

Keywords: air pollution, citrullination, in vivo, lungs

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Authors: Samane Eftekhari Ranjbar

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Diabetes mellitus, a metabolic disorder characterized by elevated blood glucose levels, ranks among the leading causes of adult mortality. This study investigates the impact of an eight-week high-intensity interval training (HIIT) program combined with sodium nitrite supplementation on TNF- α, MURF1, and PI3K in a type 2 diabetes rodent model. Elevated TNF-α levels have been associated with insulin resistance, while MURF1 and PI3K play roles in muscle atrophy and insulin signaling pathways, respectively. In this experimental study, 15 eight-week-old rats from the Sara Laboratory Center in Tabriz were assigned to one of five groups: healthy control, diabetic control, diabetic with sodium nitrite supplementation, diabetic with eight weeks of intermittent exercise, and diabetic with eight weeks of interval training plus sodium nitrite supplementation. The HIIT protocol was designed to span eight weeks, with five weekly sessions at specified intensities and durations. Sodium nitrite, known for its vasodilatory and cytoprotective properties, was administered via injection. The findings revealed that the HIIT program and sodium nitrite supplementation influenced the examined biomarkers. ANOVA test outcomes indicated statistically significant differences in TNF- α (P=0.001), MURF1 (P=0.001), and PI3K (P=0.001) concentrations among the various groups. The healthy control group exhibited substantially decreased TNF- α, and MURF1 levels, as well as elevated PI3K levels compared to the diabetic control group. The exercise group, in conjunction with sodium nitrite supplementation, demonstrated a significant rise in PI3K levels (P=0.001) and a decline in TNF- α levels (P=0.018) relative to the diabetic control group. These results suggest that the combined intervention may help improve insulin sensitivity and reduce inflammation. However, MURF1 levels, which are related to muscle atrophy, showed no significant difference (P=0.24). In conclusion, in type 2 diabetic rats, an eight-week high-intensity interval training program with sodium nitrite supplementation does not affect MURF1 levels but does influence PI3K and TNF- α levels. This combination may hold potential for improving insulin sensitivity and reducing inflammation in type 2 diabetes patients, warranting further investigation and potential translation to human clinical trials.

Keywords: high-intensity interval training, sodium nitrate supplementation, type 2 diabetes, tumor necrosis factor-alpha, phosphatidylinositol-3-kinase, muscle RING-finger protein-1

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Authors: Ron Dick, P. S. D. V. Prasadarao, Glenn Coltman

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Agenesis of the corpus callosum (ACC) is a failure to develop corpus callosum - the large bundle of fibers of the brain that connects the two cerebral hemispheres. It can occur as a partial or complete absence of the corpus callosum. In the general population, its estimated prevalence rate is 1 in 4000 and a wide range of genetic, infectious, vascular, and toxic causes have been attributed to this heterogeneous condition. The diagnosis of ACC is often achieved by neuroimaging procedures. Though persons with ACC can perform normally on intelligence tests they generally present with a range of neuropsychological and social deficits. The deficit profile is characterized by poor coordination of motor movements, slow reaction time, processing speed and, poor memory. Socially, they present with deficits in communication, language processing, the theory of mind, and interpersonal relationships. The present paper illustrates the role of neuropsychological assessment with implications to psychosocial management in a case of agenesis of the corpus callosum. Method: A 27-year old left handed Caucasian male with a history of ACC was self-referred for a neuropsychological assessment to assist him in his employment options. Parents noted significant difficulties with coordination and balance at an early age of 2-3 years and he was diagnosed with dyspraxia at the age of 14 years. History also indicated visual impairment, hypotonia, poor muscle coordination, and delayed development of motor milestones. MRI scan indicated agenesis of the corpus callosum with ventricular morphology, widely spaced parallel lateral ventricles and mild dilatation of the posterior horns; it also showed colpocephaly—a disproportionate enlargement of the occipital horns of the lateral ventricles which might be affecting his motor abilities and visual defects. The MRI scan ruled out other structural abnormalities or neonatal brain injury. At the time of assessment, the subject presented with such problems as poor coordination, slowed processing speed, poor organizational skills and time management, and difficulty with social cues and facial expressions. A comprehensive neuropsychological assessment was planned and conducted to assist in identifying the current neuropsychological profile to facilitate the formulation of a psychosocial and occupational rehabilitation programme. Results: General intellectual functioning was within the average range and his performance on memory-related tasks was adequate. Significant visuospatial and visuoconstructional deficits were evident across tests; constructional difficulties were seen in tasks such as copying a complex figure, building a tower and manipulating blocks. Poor visual scanning ability and visual motor speed were evident. Socially, the subject reported heightened social anxiety, difficulty in responding to cues in the social environment, and difficulty in developing intimate relationships. Conclusion: Persons with ACC are known to present with specific cognitive deficits and problems in social situations. Findings from the current neuropsychological assessment indicated significant visuospatial difficulties, poor visual scanning and problems in social interactions. His general intellectual functioning was within the average range. Based on the findings from the comprehensive neuropsychological assessment, a structured psychosocial rehabilitation programme was developed and recommended.

Keywords: agenesis, callosum, corpus, neuropsychology, psychosocial, rehabilitation

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Authors: Avelyno D'Costa, S. K. Shyama, M. K. Praveen Kumar

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The coast of Goa, India receives constant anthropogenic stress through its major rivers which carry mining rejects of iron and manganese ores from upstream mining sites and petroleum hydrocarbons from shipping and harbor-related activities which put the aquatic fauna such as bivalves at risk. The present study reports the pollution status of the Goan coast by the above xenobiotics employing genotoxicity studies. This is further supplemented by the quantification of total petroleum hydrocarbons (TPHs) and various trace metals (iron, manganese, copper, cadmium, and lead) in gills of the estuarine clam, Meretrix ovum as well as from the surrounding water and sediment, over a two-year sampling period, from January 2013 to December 2014. Bivalves were collected from a probable unpolluted site at Palolem and a probable polluted site at Vasco, based upon the anthropogenic activities at these sites. Genotoxicity was assessed in the gill cells using the comet assay and micronucleus test. The quantity of TPHs and trace metals present in gill tissue, water and sediments were analyzed using spectrofluorometry and atomic absorption spectrophotometry (AAS), respectively. The statistical significance of data was analyzed employing Student’s t-test. The relationship between DNA damage and pollutant concentrations was evaluated using multiple regression analysis. Significant DNA damage was observed in the bivalves collected from Vasco which is a region of high industrial activity. Concentrations of TPHs and trace metals (iron, manganese, and cadmium) were also found to be significantly high in gills of the bivalves collected from Vasco compared to those collected from Palolem. Further, the concentrations of these pollutants were also found to be significantly high in the water and sediments at Vasco compared to that of Palolem. This may be due to the lack of industrial activity at Palolem. A high positive correlation was observed between the pollutant levels and DNA damage in the bivalves collected from Vasco suggesting the genotoxic nature of these pollutants. Further, M. ovum can be used as a bioindicator species for monitoring the level of pollution of the estuarine/coastal regions by TPHs and trace metals.

Keywords: comet assay, metals, micronucleus test, total petroleum Hydrocarbons

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Authors: Franco Van De Velde, Debora Esposito, Maria E. Pirovani, Mary A. Lila

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The physiology of various inflammatory diseases is a complex process mediated by inflammatory and immune cells such as macrophages and monocytes. Chronic inflammation, as observed in many cardiovascular and autoimmune disorders, occurs when the low-grade inflammatory response fails to resolve with time. Because of the complexity of the chronic inflammatory disease, major efforts have focused on identifying novel anti-inflammatory agents and dietary regimes that prevent the pro-inflammatory process at the early stage of gene expression of key pro-inflammatory mediators and cytokines. The ability of the extracts of three blackberry cultivars (‘Jumbo’, ‘Black Satin’ and ‘Dirksen’), and one strawberry cultivar (‘Camarosa’) to inhibit four well-known genetic biomarkers of inflammation: inducible nitric oxide synthase (iNOS), cyclooxynase-2 (Cox-2), interleukin-1β (IL-1β) and interleukin-6 (IL-6) in an in vitro lipopolysaccharide-stimulated murine RAW 264.7 macrophage model were investigated. Moreover, the effect of latter extracts on the intracellular reactive oxygen species (ROS) and nitric oxide (NO) production was assessed. Assay was conducted with 50 µg/mL crude extract concentration, an amount that is easily achievable in the gastrointestinal tract after berries consumption. The mRNA expression levels of Cox-2 and IL-6 were reduced consistently (more than 30%) by extracts of ‘Jumbo’ and ‘Black Satin’ blackberries. Strawberry extracts showed high reduction in mRNA expression levels of IL-6 (more than 65%) and exhibited moderate reduction in mRNA expression of Cox-2 (more than 35%). The latter behavior mirrors the intracellular ROS production of the LPS stimulated RAW 264.7 macrophages after the treatment with blackberry ‘Black Satin’ and ‘Jumbo’, and strawberry ‘Camarosa’ extracts, suggesting that phytochemicals from these fruits may play a role in the health maintenance by reducing oxidative stress. On the other hand, effective inhibition in the gene expression of IL-1β and iNOS was not observed by any of blackberry and strawberry extracts. However, suppression in the NO production in the activated macrophages among 5–25% was observed by ‘Jumbo’ and ‘Black Satin’ blackberry extracts and ‘Camarosa’ strawberry extracts, suggesting a higher NO suppression property by phytochemicals of these fruits. All these results suggest the potential beneficial effects of studied berries as functional foods with antioxidant and anti-inflammatory roles. Moreover, the underlying role of phytochemicals from these fruits in the protection of inflammatory process will deserve to be further explored.

Keywords: cyclooxygenase-2, functional foods, interleukin-6, reactive oxygen species

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Authors: Parker Murray, Marci Johnson, Tyson S. Burnham, Alina K. Fong, Mark D. Allen, Bruce McIff

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Purpose: Pathological dysregulation of Neurovascular Coupling (NVC) caused by mild traumatic brain injury (mTBI) is the predominant source of chronic post-concussion syndrome (PCS) symptomology. fNCI has the ability to localize dysregulation in NVC by measuring blood-oxygen-level-dependent (BOLD) signaling during the performance of fMRI-adapted neuropsychological evaluations. With fNCI, 57 brain areas consistently affected by concussion were identified as PCS neural markers, which were validated on large samples of concussion patients and healthy controls. These neuromarkers provide the basis for a computation of PCS severity which is referred to as the Severity Index Score (SIS). The SIS has proven valuable in making pre-treatment decisions, monitoring treatment efficiency, and assessing long-term stability of outcomes. Methods and Materials: After being scanned while performing various cognitive tasks, 476 concussed patients received an SIS score based on the neural dysregulation of the 57 previously identified brain regions. These scans provide an objective measurement of attentional, subcortical, visual processing, language processing, and executive functioning abilities, which were used as biomarkers for post-concussive neural dysregulation. Initial SIS scores were used to develop individualized therapy incorporating cognitive, occupational, and neuromuscular modalities. These scores were also used to establish pre-treatment benchmarks and measure post-treatment improvement. Results: Changes in SIS were calculated in percent change from pre- to post-treatment. Patients showed a mean improvement of 76.5 percent (σ= 23.3), and 75.7 percent of patients showed at least 60 percent improvement. Longitudinal reassessment of 24 of the patients, measured an average of 7.6 months post-treatment, shows that SIS improvement is maintained and improved, with an average of 90.6 percent improvement from their original scan. Conclusions: fNCI provides a reliable measurement of NVC allowing for identification of concussion pathology. Additionally, fNCI derived SIS scores direct tailored therapy to restore NVC, subsequently resolving chronic PCS resulting from mTBI.

Keywords: concussion, functional magnetic resonance imaging (fMRI), neurovascular coupling (NVC), post-concussion syndrome (PCS)

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Authors: Tamphasana Wairokpam

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Inflammatory myopathies (IMs) have long been recognised as a heterogenous family of myopathies with acute, subacute, and sometimes chronic presentation and are potentially treatable. Necrotizing autoimmune myopathies (NAM) are a relatively new subset of myopathies. Patients generally present with subacute onset of proximal myopathy and significantly elevated creatinine kinase (CK) levels. It is being increasingly recognised that there are limitations to the independent diagnostic utility of muscle biopsy. Immunohistochemistry tests may reveal important information in these cases. The traditional classification of IMs failed to recognise NAM as a separate entity and did not adequately emphasize the diversity of IMs. This review and case report on NAM aims to highlight the heterogeneity of this entity and focus on the distinct clinical presentation, biopsy findings, specific auto-antibodies implicated, and available treatment options with prognosis. This article is a meta-analysis of literatures on NAM and a case report illustrating the clinical course, investigation and biopsy findings, antibodies implicated, and management of a patient with NAM. The main databases used for the search were Pubmed, Google Scholar, and Cochrane Library. Altogether, 67 publications have been taken as references. Two biomarkers, anti-signal recognition protein (SRP) and anti- hydroxyl methylglutaryl-coenzyme A reductase (HMGCR) Abs, have been found to have an association with NAM in about 2/3rd of cases. Interestingly, anti-SRP associated NAM appears to be more aggressive in its clinical course when compared to its anti-HMGCR associated counterpart. Biopsy shows muscle fibre necrosis without inflammation. There are reports of statin-induced NAM where progression of myopathy has been seen even after discontinuation of statins, pointing towards an underlying immune mechanism. Diagnosisng NAM is essential as it requires more aggressive immunotherapy than other types of IMs. Most cases are refractory to corticosteroid monotherapy. Immunosuppressive therapy with other immunotherapeutic agents such as IVIg, rituximab, mycophenolate mofetil, azathioprine has been explored and found to have a role in the treatment of NAM. In conclusion,given the heterogeneity of NAM, it appears that NAM is not just a single entity but consists of many different forms, despite the similarities in presentation and its classification remains an evolving field. A thorough understanding of underlying mechanism and the clinical correlation with antibodies associated with NAM is essential for efficacious management and disease prognostication.

Keywords: inflammatory myopathies, necrotising autoimmune myopathies, anti-SRP antibody, anti-HMGCR antibody, statin induced myopathy

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Authors: Priya Kulkarni, Soumya Koppikar, Narendrakumar Wagh, Dhanshri Ingle, Onkar Lande, Abhay Harsulkar

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Cartilage is an extracellular matrix composed of aggrecan, which imparts it with a great tensile strength, stiffness and resilience. Disruption in cartilage metabolism leading to progressive degeneration is a characteristic feature of Osteoarthritis (OA). The process involves enzymatic depolymerisation of cartilage specific proteoglycan, releasing free glycosaminoglycan (GAG). This released GAG in synovial fluid (SF) of knee joint serves as a direct measure of cartilage loss, however, limited due to its invasive nature. Western Ontario and McMaster Universities Arthritis Index (WOMAC) is widely used for assessing pain, stiffness and physical-functions in OA patients. The scale is comprised of three subscales namely, pain, stiffness and physical-function, intends to measure patient’s perspective of disease severity as well as efficacy of prescribed treatment. Twenty SF samples obtained from OA patients were analysed for their GAG values in SF using DMMB based assay. LK 1.0 vernacular version was used to attain WOMAC scale. The results were evaluated using SAS University software (Edition 1.0) for statistical significance. All OA patients revealed higher GAG values compared to the control value of 78.4±30.1µg/ml (obtained from our non-OA patients). Average WOMAC calculated was 51.3 while pain, stiffness and function estimated were 9.7, 3.9 and 37.7, respectively. Interestingly, a strong statistical correlation was established between WOMAC function subscale and GAG (p = 0.0102). This subscale is based on day-to-day activities like stair-use, bending, walking, getting in/out of car, rising from bed. However, pain and stiffness subscale did not show correlation with any of the studied markers and endorsed the atypical inflammation in OA pathology. On one side, where knee pain showed poor correlation with GAG, it is often noted that radiography is insensitive to cartilage degenerative changes; thus OA remains undiagnosed for long. Moreover, active cartilage degradation phase remains elusive to both, patient and clinician. Through analysis of large number of OA patients we have established a close association of Kellgren-Lawrence grades and increased cartilage loss. A direct attempt to correlate WOMAC and radiographic progression of OA with various biomarkers has not been attempted so far. We found a good correlation in GAG levels in SF and the function subscale.

Keywords: cartilage, Glycosaminoglycan, synovial fluid, western ontario and McMaster Universities Arthritis Index

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Authors: Jae-Hyeon Kim, Michael Lee

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Intrinsic and acquired resistance limits the therapeutic benefits of oncogenic BRAF inhibitors in melanoma. MicroRNAs (miRNA) regulate the expression of target mRNAs by repressing their translation. Thus, we investigated miRNA expression patterns in melanoma cell lines to identify candidate biomarkers for acquired resistance to BRAF inhibitor. Here, we used Affymetrix miRNA V3.0 microarray profiling platform to compare miRNA expression levels in three cell lines containing BRAF inhibitor-sensitive A375P BRAF V600E cells, their BRAF inhibitor-resistant counterparts (A375P/Mdr), and SK-MEL-2 BRAF-WT cells with intrinsic resistance to BRAF inhibitor. The miRNAs with at least a two-fold change in expression between BRAF inhibitor-sensitive and –resistant cell lines, were identified as differentially expressed. Averaged intensity measurements identified 138 and 217 miRNAs that were differentially expressed by 2 fold or more between: 1) A375P and A375P/Mdr; 2) A375P and SK-MEL-2, respectively. The hierarchical clustering revealed differences in miRNA expression profiles between BRAF inhibitor-sensitive and –resistant cell lines for miRNAs involved in intrinsic and acquired resistance to BRAF inhibitor. In particular, 43 miRNAs were identified whose expression was consistently altered in two BRAF inhibitor-resistant cell lines, regardless of intrinsic and acquired resistance. Twenty five miRNAs were consistently upregulated and 18 downregulated more than 2-fold. Although some discrepancies were detected when miRNA microarray data were compared with qPCR-measured expression levels, qRT-PCR for five miRNAs (miR-3617, miR-92a1, miR-1246, miR-1936-3p, and miR-17-3p) results showed excellent agreement with microarray experiments. To further investigate cellular functions of miRNAs, we examined effects on cell proliferation. Synthetic oligonucleotide miRNA mimics were transfected into three cell lines, and proliferation was quantified using a colorimetric assay. Of the 5 miRNAs tested, only miR-1246 altered cell proliferation of A375P/Mdr cells. The transfection of miR-1246 mimic strongly conferred PLX-4720 resistance to A375P/Mdr cells, implying that miR-1246 upregulation confers acquired resistance to BRAF inhibition. We also found that PLX-4720 caused much greater G2/M arrest in A375P/Mdr cells transfected with miR-1246mimic than that seen in scrambled RNA-transfected cells. Additionally, miR-1246 mimic partially caused a resistance to autophagy induction by PLX-4720. These results indicate that autophagy does play an essential death-promoting role inPLX-4720-induced cell death. Taken together, these results suggest that miRNA expression profiling in melanoma cells can provide valuable information for a network of BRAF inhibitor resistance-associated miRNAs.

Keywords: microRNA, BRAF inhibitor, drug resistance, autophagy

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Authors: Mohamed Malek Khenissi, Mohamed Montassar Ben Slama, Anis Belhaj Mohamed, Moncef Saidi

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Northern Tunisia is well known by its different and complex structural and geological zones that have been the result of a geodynamic history that extends from the early Mesozoic era to the actual period. One of these zones is the salt province, where the Halokinesis process is manifested by a number of NE/SW salt structures such as Jebel Ech-Cheid which represents masses of materials characterized by a high plasticity and low density. The salt masses extrusions that have been developed due to an extension that started from the late Triassic to late Cretaceous. The evolution of salt bodies within sedimentary basins have not only contributed to modify the architecture of the basin, but it also has certain geochemical effects which touch mainly source rocks that surround it. It has been demonstrated that the presence of salt structures within sedimentary basins can influence its temperature distribution and thermal history. Moreover, it has been creating heat flux anomalies that may affect the maturity of organic matter and the timing of hydrocarbon generation. Field samples of the Bahloul source rock (Cenomanan-Tunonian) were collected from different sights from all around Ech Cheid salt structure and evaluated using Rock-eval pyrolysis and GC/MS techniques in order to assess the degree of maturity evolution and the heat flux anomalies in the different zones analyze. The Total organic Carbon (TOC) values range between 1 to 9% and the (Tmax) ranges between 424 and 445°C, also the distribution of the source rock biomarkers both saturated and aromatic changes in a regular fashions with increasing maturity and this are shown in the chromatography results such as Ts/(Ts+Tm) ratios, 22S/(22S+22R) values for C31 homohopanes, ββ/(ββ+αα)20R and 20S/(20S+20R) ratios for C29 steranes which gives a consistent maturity indications and assessment of the field samples. These analyses are carried to interpret the maturity evolution and the heat flux around Ech Cheid salt structure through the geological history. These analyses also aim to demonstrate that the salt structure can have a direct effect on the geothermal gradient of the basin and on the maturity of the Bahloul Formation source rock. The organic matter has reached different stages of thermal maturity, but delineate a general increasing maturity trend. Our study confirms that the J. Ech Cheid salt body have on the first hand: a huge influence on the local distribution of anoxic depocentre at least within Cenomanian-Turonian time. In the second hand, the thermal anomaly near the salt mass has affected the maturity of Bahloul Formation.

Keywords: Bahloul formation, depocentre, GC/MS, rock-eval

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Authors: Alexander Heckman, Rohan Goswami, Zachi Attia, Paul Friedman, Peter Noseworthy, Demilade Adedinsewo, Pablo Moreno-Franco, Rickey Carter, Tathagat Narula

Abstract:

Background: Postoperative atrial fibrillation (POAF) is associated with adverse health consequences, higher costs, and longer hospital stays. Utilizing existing predictive models that rely on clinical variables and circulating biomarkers, multiple societies have published recommendations on the treatment and prevention of POAF. Although reasonably practical, there is room for improvement and automation to help individualize treatment strategies and reduce associated complications. Methods and Results: In this retrospective cohort study of solid organ transplant recipients, we evaluated the diagnostic utility of a previously developed AI-based ECG prediction for silent AF on the development of POAF within 30 days of transplant. A total of 2261 non-cardiac transplant patients without a preexisting diagnosis of AF were found to have a 5.8% (133/2261) incidence of POAF. While there were no apparent sex differences in POAF incidence (5.8% males vs. 6.0% females, p=.80), there were differences by race and ethnicity (p<0.001 and 0.035, respectively). The incidence in white transplanted patients was 7.2% (117/1628), whereas the incidence in black patients was 1.4% (6/430). Lung transplant recipients had the highest incidence of postoperative AF (17.4%, 37/213), followed by liver (5.6%, 56/1002) and kidney (3.6%, 32/895) recipients. The AUROC in the sample was 0.62 (95% CI: 0.58-0.67). The relatively low discrimination may result from undiagnosed AF in the sample. In particular, 1,177 patients had at least 1 AI-ECG screen for AF pre-transplant above .10, a value slightly higher than the published threshold of 0.08. The incidence of POAF in the 1104 patients without an elevated prediction pre-transplant was lower (3.7% vs. 8.0%; p<0.001). While this supported the hypothesis that potentially undiagnosed AF may have contributed to the diagnosis of POAF, the utility of the existing AI-ECG screening algorithm remained modest. When the prediction for POAF was made using the first postoperative ECG in the sample without an elevated screen pre-transplant (n=1084 on account of n=20 missing postoperative ECG), the AUROC was 0.66 (95% CI: 0.57-0.75). While this discrimination is relatively low, at a threshold of 0.08, the AI-ECG algorithm had a 98% (95% CI: 97 – 99%) negative predictive value at a sensitivity of 66% (95% CI: 49-80%). Conclusions: This study's principal finding is that the incidence of POAF is rare, and a considerable fraction of the POAF cases may be latent and undiagnosed. The high negative predictive value of AI-ECG screening suggests utility for prioritizing monitoring and evaluation on transplant patients with a positive AI-ECG screening. Further development and refinement of a post-transplant-specific algorithm may be warranted further to enhance the diagnostic yield of the ECG-based screening.

Keywords: artificial intelligence, atrial fibrillation, cardiology, transplant, medicine, ECG, machine learning

Procedia PDF Downloads 94

Authors: Danna Jia, Bin Li

Abstract:

Background: Atopic dermatitis (AD) is a chronic and refractory inflammatory skin disease characterized by relapsing eczematous and pruritic skin lesions. The global prevalence of AD ranges from 1~ 20%, and its incidence rates are increasing. It affects individuals from infancy to adulthood, significantly impacting their daily lives and social activities. Despite its major health burden, the precise mechanisms underlying AD remain unknown. Understanding the genetic differences associated with AD is crucial for advancing diagnosis and targeted treatment development. This study aims to identify candidate genes of AD by using bioinformatics analysis. Methods: We conducted a comprehensive analysis of four pooled transcriptomic datasets (GSE16161, GSE32924, GSE130588, and GSE120721) obtained from the Gene Expression Omnibus (GEO) database. Differential gene expression analysis was performed using the R statistical language. The differentially expressed genes (DEGs) between AD patients and normal individuals were functionally analyzed using Gene Ontology (GO) and the Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment. Furthermore, a protein-protein interaction (PPI) network was constructed to identify candidate genes. Results: Among the patient-level gene expression datasets, we identified 114 shared DEGs, consisting of 53 upregulated genes and 61 downregulated genes. Functional analysis using GO and KEGG revealed that the DEGs were mainly associated with the negative regulation of transcription from RNA polymerase II promoter, membrane-related functions, protein binding, and the Human papillomavirus infection pathway. Through the PPI network analysis, we identified eight core genes: CD44, STAT1, HMMR, AURKA, MKI67, and SMARCA4. Conclusion: This study elucidates key genes associated with AD, providing potential targets for diagnosis and treatment. The identified genes have the potential to contribute to the understanding and management of AD. The bioinformatics analysis conducted in this study offers new insights and directions for further research on AD. Future studies can focus on validating the functional roles of these genes and exploring their therapeutic potential in AD. While these findings will require further verification as achieved with experiments involving in vivo and in vitro models, these results provided some initial insights into dysfunctional inflammatory and immune responses associated with AD. Such information offers the potential to develop novel therapeutic targets for use in preventing and treating AD.

Keywords: atopic dermatitis, bioinformatics, biomarkers, genes

Procedia PDF Downloads 51