Search results for: renal fibrosis signaling pathway

Authors: Faris Tarlochan, Siva Mahesh Tangutooru

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Lateral Geniculate Nucleus (LGN) is the relay center in the visual pathway as it receives most of the input information from retinal ganglion cells (RGC) and sends to visual cortex. Low threshold calcium currents (IT) at the membrane are the unique indicator to characterize this firing functionality of the LGN neurons gained by the RGC input. According to the LGN functional requirements such as functional mapping of RGC to LGN, the morphologies of the LGN neurons were developed. During the neurological disorders like glaucoma, the mapping between RGC and LGN is disconnected and hence stimulating LGN electrically using deep brain electrodes can restore the functionalities of LGN. A computational model was developed for simulating the LGN neurons with three predominant morphologies, each representing different functional mapping of RGC to LGN. The firings of action potentials at LGN neuron due to IT were characterized by varying the stimulation parameters, morphological parameters and orientation. A wide range of stimulation parameters (stimulus amplitude, duration and frequency) represents the various strengths of the electrical stimulation with different morphological parameters (soma size, dendrites size and structure). The orientation (0-1800) of LGN neuron with respect to the stimulating electrode represents the angle at which the extracellular deep brain stimulation towards LGN neuron is performed. A reduced dendrite structure was used in the model using Bush–Sejnowski algorithm to decrease the computational time while conserving its input resistance and total surface area. The major finding is that an input potential of 0.4 V is required to produce the action potential in the LGN neuron which is placed at 100 µm distance from the electrode. From this study, it can be concluded that the neuroprostheses under design would need to consider the capability of inducing at least 0.4V to produce action potentials in LGN.

Keywords: Lateral Geniculate Nucleus, visual cortex, finite element, glaucoma, neuroprostheses

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Authors: Anukriti Verma, Bhawna Rathi, Shivani Sharda

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Reactive Arthritis (ReA) is a disorder that causes inflammation in joints due to certain infections at distant sites in the body. ReA begins with stiffness, pain, and inflammation in these areas especially the ankles, knees, and hips. It gradually causes several complications such as conjunctivitis in the eyes, skin lesions in hand, feet and nails and ulcers in the mouth. Nowadays the diagnosis of ReA is based upon a differential diagnosis pattern. The parameters for differentiating ReA from other similar disorders include physical examination, history of the patient and a high index of suspicion. There are no standard lab tests or markers available for ReA hence the early diagnosis of ReA becomes difficult and the chronicity of disease increases with time. It is reported that enteric disorders such as Inflammatory Bowel Disease (IBD) that is inflammation in gastrointestinal tract namely Crohn’s Disease (CD) and Ulcerative Colitis (UC) are reported to be linked with ReA. Several microorganisms are found such as Campylobacter, Salmonella, Shigella and Yersinia causing IBD leading to ReA. The aim of our study was to perform the in-silico analysis in order to find interactions between microorganisms and human host causing IBD leading to ReA. A systems biology approach for metabolic network reconstruction and simulation was used to find the essential genes of the reported microorganisms. Interactomics study was used to find the interactions between the pathogen genes and human host. Genes such as nhaA (pathogen), dpyD (human), nagK (human) and kynU (human) were obtained that were analysed further using the functional, pathway and network analysis. These genes can be used as putative drug targets and biomarkers in future for early diagnosis, prevention, and treatment of IBD leading to ReA.

Keywords: drug targets, inflammatory bowel disease, reactive arthritis, systems biology

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Authors: Ajay Kumar, Satwinderjeet Kaur

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Onosma bracteata Wall. (Boraginaceae), is known to be a medicinal plant, useful in the treatment of body swellings, abdominal pain and urinary calculi, etc. The present study focused on the radical scavenging and cancer growth inhibitory properties of isolates from O. bracteata. Obea fraction demonstrated noticeable free radical scavenging ability along with antiproliferative activity in human osteosarcoma MG-63, human neuroblastoma IMR-32, and human lung cancer A549 cell lines using MTT assay with GI50 values of 88.56, 101.61 and 112.7 μg/ml, respectively. The scanning electron and confocal microscopy studies showed morphological alterations including nuclear condensation and formation of apoptotic bodies in osteosarcoma MG-63 cells. Obea fraction in osteosarcoma MG-63 cells augmented the reactive oxygen species (ROS) level and decreased the mitochondrial membrane potential. Flow cytometry analysis revealed the Obea treated cells to be arrested in the G0/G1 phase in a dose dependent manner supported by the observed increase in the early apoptotic cell population. Western blotting analysis showed that the expression of p-NF-kB, COX-2, p-Akt, and Bcl-xL decreased whereas, the expression of GSK-3β, p53, caspase-3 and caspase-9 proteins increased. The downregulation of Bcl-2, Cyclin E, CDK2 and mortalin gene expression and upregulation of p53 genes was unfolded in RT-qPCR studies. The presence of catechin, kaempferol, Onosmin A and epicatechin, as revealed in high-performance liquid chromatography (HPLC) studies, contributes towards the chemopreventive potential of O. bracteata which can be tapped for chemotherapeutic use.

Keywords: apoptosis, confocal microscopy, HPLC, mitochondria membrane potential, reactive oxygen species

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Authors: Arnab Hazra

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Breath analysis is a quick, noninvasive and inexpensive technique for disease diagnosis can be used on people of all ages without any risk. Only a limited number of volatile organic compounds (VOCs) can be associated with the occurrence of specific diseases. These VOCs can be considered as disease markers or breath markers. Selective detection with specific concentration of breath marker in exhaled human breath is required to detect a particular disease. For example, acetone (C₃H₆O), ethanol (C₂H₅OH), ethane (C₂H₆) etc. are the breath markers and abnormal concentrations of these VOCs in exhaled human breath indicates the diseases like diabetes mellitus, renal failure, breast cancer respectively. Nanomaterial-based vapor sensors are inexpensive, small and potential candidate for the detection of breath markers. In practical measurement, selectivity is the most crucial issue where trace detection of breath marker is needed to identify accurately in the presence of several interfering vapors and gases. Current article concerns a novel technique for selective and lower ppb level detection of breath markers at very low temperature based on TiO₂ nanotube array based vapor sensor devices. Highly ordered and oriented TiO₂ nanotube array was synthesized by electrochemical anodization of high purity tatinium (Ti) foil. 0.5 wt% NH₄F, ethylene glycol and 10 vol% H₂O was used as the electrolyte and anodization was carried out for 90 min with 40 V DC potential. Au/TiO₂ Nanotube/Ti, sandwich type sensor device was fabricated for the selective detection of VOCs in low concentration range. Initially, sensor was characterized where resistive and capacitive change of the sensor was recorded within the valid concentration range for individual breath markers (or organic vapors). Sensor resistance was decreased and sensor capacitance was increased with the increase of vapor concentration. Now, the ratio of resistive slope (mR) and capacitive slope (mC) provided a concentration independent constant term (M) for a particular vapor. For the detection of unknown vapor, ratio of resistive change and capacitive change at any concentration was same to the previously calculated constant term (M). After successful identification of the target vapor, concentration was calculated from the straight line behavior of resistance as a function of concentration. Current technique is suitable for the detection of particular vapor from a mixture of other interfering vapors.

Keywords: breath marker, vapor sensors, selective detection, TiO₂ nanotube array

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Authors: Hsiao-Chien Tsai, Yu-Pin Chen, Ruei-Ming Chen

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Introduction: Osteoarthritis (OA) is characterized by joint destruction and causes chronic disability. One of the prominent symptoms is pain. Alleviating the pain is necessary and urgent for the therapy of OA patients. However, currently, understanding the mechanisms that drive OA-induced pain remains challenging, which hampers the optimistic management of pain in OA patients. Semaphorin 4D (Sema4D) participates in axon guidance pathway and bone remodeling, thus, may play a role in the regulation of pain in OA. In this study, we have established a rat model of OA to find out the mechanisms of OA-induced pain and to deliberate the roles of Sema4D. Methods: Behavioral changes and the pro-inflammatory cytokines (IL-1β, TNF-α, and IL-17) associated with pain were measured during the development of OA. Sema4D expression in cartilage and synovial membrane at 1, 4, and 12 weeks after inducing OA was analyzed. To assess if Sema4D is related to the neurogenesis in OA as an axon repellant, we analyzed the expression of PGP9.5 as well. Results: Synovitis and cartilage degradation were evident histologically during the development of OA. Mechanical hyperalgesia was most severe at week 1, then persisted thereafter. It was associated with stress coping strategies. Similar to the pain behavioral results, levels of IL-1β and TNF-α in synovial lavage fluid were significantly elevated in the OA group at weeks 1 and 4, respectively. Sema4D expression in cartilage and the synovial membrane was also enhanced in the OA group and was correlated with pain and pro-inflammatory cytokines. The marker of neurogenesis, PGP9.5, was also enhanced during the development of OA. Discussion: OA induced mechanical hyperalgesia, which might be through upregulating IL-1β/TNF-α-mediated Sema4D expressions. If anti-Sema4D treatment could reduce OA-induced mechanical hyperalgesia and prevent the subsequent progression of OA needs to be further investigated. Significance: OA can induce mechanical hyperalgesia through upregulation of IL-1β/TNF-α-mediated Sema4D and PGP9.5 expressions. And the upregulation of Sema4D may indicate the severity or active status of OA and OA-induced pain.

Keywords: traumatic osteoarthritis, mechanical hyperalgesia, Sema4D, inflammatory cytokines

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Authors: Malihe Moeinin, Robert Hill, Ferranti Wong

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Background: A white spot lesion (WSL) is defined as subsurface enamel porosity from carious demineralisation on the smooth surfaces of the tooth. It appears as a milky white opacity. Lesions shown an apparently intact surface layer, followed underneath by the more porous lesion body. The small pores within the body of the lesion act as diffusion pathway for both acids and minerals, so allowing the demineralisation of enamel to occur at the advancing front of the lesion. Objectives: The objective is to mapthe porosity and its size on WSL with Focused Ion Bean- Scanning Electron Microscopy (FIB-SEM) Method: The basic method used for FIB-SEM consisted of depositing a one micron thick layer of platinum over 25μmx 25μm of the interest region of enamel. Then, making a rough cut (25μmx 5μmx 20μm) with 3nA current and 30Kv was applied with the help of drift suppression (DS), using a standard “cross-sectional” cutting pattern, which ended at the front of the deposited platinum layer. Two adjacent areas (25μmx 5μmx 20μm) on the both sides of the platinum layer were milled under the same conditions. Subsequent, cleaning cross-sections were applied to polish the sub-surface edge of interest running perpendicular to the surface. The "slice and view" was carried out overnight for milling almost 700 slices with 2Kv and 4nA and taking backscattered (BS) images. Then, images were imported into imageJ and analysed. Results: The prism structure is clearly apparent on FIB-SEM slices of WSL with the dissolution of prism boundaries as well as internal porosity within the prism itself. Porosity scales roughly 100-400nm, which is comparable to the light wavelength (500nm). Conclusion: FIB-SEM is useful to characterize the porosity of WSL and it clearly shows the difference between WSL and normal enamel.

Keywords: white spot lesion, FIB-SEM, enamel porosity, porosity

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Authors: Dipali Dhawan

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Cancerous epithelial cells are confined to a primary site by the continued expression of adhesion molecules and the intact basal lamina. However, as the cancer progresses some cells are believed to undergo an epithelial-mesenchymal transition (EMT) event, leading to increased motility, invasion and, ultimately, metastasis of the cells from the primary tumour to secondary sites within the body. These disseminated cancer cells need the ability to self-renew, as stem cells do, in order to establish and maintain a heterogeneous metastatic tumour mass. Identification of the specific subpopulation of cancer stem cells amenable to the process of metastasis is highly desirable. In this study, we have isolated and characterized cancer stem cells from luminal and basal breast cancer cell lines (MDA-MB-231, MDA-MB-453, MDA-MB-468, MCF7 and T47D) on the basis of cell surface markers CD44 and CD24; as well as Side Populations (SP) using Hoechst 33342 dye efflux. The isolated populations were analysed for epithelial and mesenchymal markers like E-cadherin, N-cadherin, Sfrp1 and Vimentin by Western blotting and Immunocytochemistry. MDA-MB-231 cell lines contain a major population of CD44+CD24- cells whereas MCF7, T47D and MDA-MB-231 cell lines show a side population. We observed higher expression of N-cadherin in MCF-7 SP cells as compared to MCF-7NSP (Non-side population) cells suggesting that the SP cells are mesenchymal like cells and hence express increased N-cadherin with stem cell-like properties. There was an expression of Sfrp1 in the MCF7- NSP cells as compared to no expression in MCF7-SP cells, which suggests that the Wnt pathway is expressed in the MCF7-SP cells. The mesenchymal marker Vimentin was expressed only in MDA-MB-231 cells. Hence, understanding the breast cancer heterogeneity would enable a better understanding of the disease progression and therapeutic targeting.

Keywords: cancer stem cells, epithelial to mesenchymal transition, biomarkers, breast cancer

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Authors: Kadeejah Alsolami, Zainab Alrefay, Husaam Awad

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Obesity and vitamin D deficiency have both been related to cardiovascular disease. The present work aimed to investigate the possible protective effect of vitamin D on cardiac apoptosis in a rat model of dietary-induced obesity. Methods: 30 male Wistar rats included in this study. They were allocated into 4 groups: Control (n=5), animal were fed standard diet for 3 months: Control + vitamin D (VD) (n=5),animals were fed a standard diet with 400IU VD/kg for 3 months: hypercaloric diets group (n=10), animals were fed a high fat diet for 3 months: hypercaloric diet with VD group (n=10), animals were fed a high fat diet with 400IU VD/kg for 3 months. At the beginning of the experiment, the weight and length were measured to assess body mass index (BMI) and repeated every 45 days. Food intake and body weight were monitored throughout the study period. Then rats were sacrificed and heart tissues collected for Quantitative Real-time polymerase chain reaction (qRT-PCR). qRT-PCR used to detect different genetic markers of apoptosis (anti-apoptotic gene (BCL2), a pro-apoptotic gene(BAX), pro-apoptotic genes (FAS, FAS-L), tumour necrosis factor (TNF), mitogen-activated protein kinases (MAPK). Results: FAS and FAS-L gene expression were significantly upregulated in rats fed with high fat diet. And FAS-L gene expression was significantly upregulated in all groups on comparison with control. Whereas Bax gene expression was significantly downregulated in rats fed with high-fat diet supplied with vitamin D. TNF was significantly upregulated in rats fed with high-fat diet treated with vitamin D. MAPK was significantly upregulated in rats fed with high fat diet group, and in rats fed with high-fat diet supplied with vitamin D. Conclusion: The cardiac apoptotic pathways were more activated in rats fed with high-fat than lean rats. And vitamin D protect the heart from the cardiac mitochondrial-dependent apoptotic pathway.

Keywords: apoptosis, heart, obesity, Vitamin D

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Authors: Amna J. Ghith, Khaled Abu Zid, Khairia Youssef, Nasser Saad

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Backgrounds: The multikinase and vascular endothelial growth factor (VEGF) receptor inhibitors interrupt the pathway by which angiogenesis becomes established and promulgated, resulting in the inadequate nourishment of metastatic disease. VEGFR-2 has been the principal target of anti-angiogenic therapies. We disclose the new thieno pyrimidines as inhibitors of VEGFR-2 designed by a molecular modeling approach with increased synergistic activity and decreased side effects. Purpose: 2-substituted thieno pyrimidines are designed and synthesized with anticipated anticancer activity based on its in silico molecular docking study that supports the initial pharmacophoric hypothesis with a same binding mode of interaction at the ATP-binding site of VEGFR-2 (PDB 2QU5) with high docking score. Methods: A series of compounds were designed using discovery studio 4.1/CDOCKER with a rational that mimic the pharmacophoric features present in the reported active compounds that targeted VEGFR-2. An in silico ADMET study was also performed to validate the bioavailability of the newly designed compounds. Results: The Compounds to be synthesized showed interaction energy comparable to or within the range of the benzimidazole inhibitor ligand when docked with VEGFR-2. ADMET study showed comparable results most of the compounds showed absorption within (95-99) zone varying according to different substitutions attached to thieno pyrimidine ring system. Conclusions: A series of 2-subsituted thienopyrimidines are to be synthesized with anticipated anticancer activity and according to docking study structure requirement for the design of VEGFR-2 inhibitors which can act as powerful anticancer agents.

Keywords: docking, discovery studio 4.1/CDOCKER, heterocycles based anticancer agents, 2-subsituted thienopyrimidines

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Authors: Hakan Duger, Alparslan Ersoy, Canan Ersoy

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Diabetes mellitus is the most common etiology of end-stage renal disease (ESRD). Also, diabetic nephropathy is the etiology of ESRD in approximately 23% of kidney transplant recipients. A successful kidney transplant improves the quality of life and reduces the mortality risk for most patients. However, patients require close follow-up after transplantation due to medical complications. Diabetes mellitus can affect patient morbidity and mortality due to possible effects of immunosuppressive therapy on glucose metabolism. We compared the frequency of medical complications and the outcomes in diabetic and non-diabetic kidney transplant recipients. Materials and Methods: This retrospective study conducted in 498 patients who underwent kidney transplant surgery at our center in 10-year periods. The patients were divided into two groups: diabetics (46 ± 10 year, 26 males, 16 females) and non-diabetics (39 ± 12 year, 259 males, 197 females). The medical complications, graft functions, causes of graft loss and death were obtained from medical records. Results: There was no significant difference between recipient age, duration of dialysis, body mass index, gender, donor type, donor age, dialysis type, histories of HBV, HCV and coronary artery disease between two groups. The history of hypertension in diabetics was higher (69% vs. 36%, p < 0.001). The ratios of hypertension (50.1% vs. 57.1%), pneumonia (21.9% vs. 20%), urinary infection (16.9% vs. 20%), transaminase elevation (11.5% vs. 20%), hyperpotasemia (14.7% vs. 17.1%), hyponatremia (9.7% vs. 20%), hypotension (7.1% vs. 7.9%), hypocalcemia (1.4% vs. 0%), thrombocytopenia (8.6% vs. 8.6%), hypoglycemia (0.7% vs. 0%) and neutropenia (1.8% vs. 0%) were comparable in non-diabetic and diabetic groups, respectively. The frequency of hyperglycaemia in diabetics was higher (8.6% vs. 54.3%, p < 0.001). After transplantation, primary non-function (3.4% vs. 2.6%), delayed graft function (25.1% vs. 34.2%) and acute rejection (7.3% vs. 10.5%) ratios of in non-diabetic and diabetic groups were similar, respectively. Hospitalization durations in non-diabetics and diabetics were 22.5 ± 17.5 and 18.7 ± 13 day (p=0.094). Mean serum creatinine levels in non-diabetics and diabetics were 1.54 ± 0.74 and 1.52 ± 0.62 mg/dL at 6th month. Forty patients had graft loss. The ratios of graft loss and death in non-diabetic and diabetic groups were 8.2% vs. 7.1% and 7.1% vs. 2.6% (p > 0.05). There was no significant relationship between graft and patient survivals with the development of medical complication. Conclusion: As a result, medical complications are common in the early period. Hyperglycaemia was frequently seen following transplantation due to the effects of immunosuppressant regimens. However, the frequency of other medical complications in diabetic patients did not differ from non-diabetic one. The most important cause of death is still infections. The development of medical complications during the first 6 months did not significantly affect transplant outcomes.

Keywords: kidney transplantation, diabetes mellitus, complication, graft function

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Authors: Ksenija Milošević, Davor Lončarević, Tihana Mudrinić, Jasmina Dostanić

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Heterogeneous photocatalytic processes have gained growing interest as an efficient method to generate hydrogen by using clean energy sources and degrading various organic pollutants. The main obstacles that restrict efficient photoactivity are narrow light-response range and high rates of charge carrier recombination. The formation of heterojunction by combining a semiconductor with low VB and a semiconductor with high CB and a suitable band gap was found to be an efficient method to prepare more sensible materials with improved charge separation, appropriate oxidation and reduction ability, and enhanced visible-light harvesting. In our research, various binary heterojunction systems based on the wide-band gap (TiO₂) and narrow bandgap (g-C₃N₄, CuO, and Co₂O₃) photocatalyst were studied. The morphology, optical, and electrochemical properties of the photocatalysts were analyzed by X-ray diffraction (XRD), scanning electron microscopy (FE-SEM), N₂ physisorption, diffuse reflectance measurements (DRS), and Mott-Schottky analysis. The photocatalytic performance of the synthesized catalysts was tested in single and simultaneous systems. The synthesized photocatalysts displayed good adsorption capacity and enhanced visible-light photocatalytic performance. The mutual interactions of pollutants on their adsorption and degradation efficiency were investigated. The interfacial connection between photocatalyst constituents and the mechanism of the transport pathway of photogenerated charge species was discussed. A radical scavenger study revealed the interaction mechanisms of the photocatalyst constituents in single and multiple pollutant systems under solar and visible light irradiation, indicating the type of heterojunction system (Z scheme or type II).

Keywords: bandgap alignment, heterojunction, photocatalysis, reaction mechanism

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Authors: Sujana T, Kurniasari MD, Ayakeding AM

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Background: Sexual violence is one of the violence with high incidence in Indonesia. Purpose: This research aims to describe the implementation of sexual violence victim assessment in Semarang Regency. Method: This research is a qualitative research with embeded single case study design. Data is analized with two units of analysis. The first unit of analysis is victim’s examiner with minimum one year of work experience. Semi-structured interview method is used to obtain the data. The second unit of analysis is document related. The data is taken by observing the pathway and description of every document and how it supported each implementation of assessment. Results: This study is resulted with three themes, which are: The first theme is assessments of sexual violence in Semarang regency has been standardized. The laws of the Republic of Indonesia have regulated the handling of victims of sexual violence in outline. Victims of sexual violence can be dealt with by the police, the Integrated Service Center for Women and Children Empowerment and the Regional General Hospital. Each examination site has different operational procedures standards for dealing with victims of sexual violence. Cooperation with family and witnesses is also required in the review process to obtain accurate results and evidence; The second idea that resulted from this study is there are inhibits factors in the assessments process. Victims sometimes feel embarrassed and reluctant to recount the chronological events during reporting. The examining officer should be able to approach and build a trust to convince the victim to be able to cooperate. The third theme is there are other things to consider in the process of assessing victims of sexual violence. Ensuring implementation in accordance with applicable operational procedures standards, providing exclusive examination rooms, counseling and safeguarding the privacy of victims are important to be considered in the assessment.

Keywords: assessment, case study, Semarang regency, sexual violence

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Authors: Nour S. Abdelrahman, Seunghyun Hong, Hassan A. Arafat, Daniel Choi, Faisal Al Marzooqi

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Abstract—The advancement of lithium extraction methods from water sources, particularly saltwater brine, is gaining prominence in the lithium recovery industry due to its cost-effectiveness. Traditional techniques like recrystallization, chemical precipitation, and solvent extraction for metal recovery from seawater or brine are energy-intensive and exhibit low efficiency. Moreover, the extensive use of organic solvents poses environmental concerns. As a result, there's a growing demand for environmentally friendly lithium recovery methods. Membrane-based separation technology has emerged as a promising alternative, offering high energy efficiency and ease of continuous operation. In our study, we explored the potential of lithium-selective sieve channels constructed from layers of 2D graphene oxide and MXene (transition metal carbides and nitrides), integrated with surface – SO₃₋ groups. The arrangement of these 2D sheets creates interplanar spacing ranging from 0.3 to 0.8 nm, which forms a barrier against multivalent ions while facilitating lithium-ion movement through nano capillaries. The introduction of the sulfonate group provides an effective pathway for Li⁺ ions, with a calculated binding energy of Li⁺ – SO³⁻ at – 0.77 eV, the lowest among monovalent species. These modified membranes demonstrated remarkably rapid transport of Li⁺ ions, efficiently distinguishing them from other monovalent and divalent species. This selectivity is achieved through a combination of size exclusion and varying binding affinities. The graphene oxide channels in these membranes showed exceptional inter-cation selectivity, with a Li⁺/Mg²⁺ selectivity ratio exceeding 104, surpassing commercial membranes. Additionally, these membranes achieved over 94% rejection of MgCl₂.

Keywords: ion permeation, lithium extraction, membrane-based separation, nanotechnology

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Authors: Shilpi, Indu Gaur, Neha Bhadauria, Susmita Goswami, Prabir K. Paul

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Cultivation and consumption of organically grown fruits and vegetables have increased by several folds. However, the presence of Human Enteric Pathogens on the surface of organically grown vegetables causing Gastro-intestinal diseases, are most likely due to contaminated water and fecal matter of farm animals. Human Enteric Pathogens are adapted to colonize the human gut, and also colonize plant surface. Microbes on plant surface communicate with each other to establish quorum sensing. The cross talk study is important because the enteric pathogens on phylloplane have been reported to mask the beneficial resident bacteria of plant. In the present study, HEPs and bacterial colonizers were identified using 16s rRNA sequencing. Microbial colonization patterns after interaction between Human Enteric Pathogens and natural bacterial residents on tomato phylloplane was studied. Tomato plants raised under aseptic conditions were inoculated with a mixture of Serratia fonticola and Klebsiella pneumoniae. The molecules involved in cross-talk between Human Enteric Pathogens and regular bacterial colonizers were isolated and identified using molecular techniques and HPLC. The colonization pattern was studied by leaf imprint method after 48 hours of incubation. The associated protein-protein interaction in the host cytoplasm was studied by use of crosslinkers. From treated leaves the crosstalk molecules and interaction proteins were separated on 1D SDS-PAGE and analyzed by MALDI-TOF-TOF analysis. The study is critical in understanding the molecular aspects of HEP’s adaption to phylloplane. The study revealed human enteric pathogens aggressively interact among themselves and resident bacteria. HEPs induced establishment of a signaling cascade through protein-protein interaction in the host cytoplasm. The study revealed that the adaptation of Human Enteric Pathogens on phylloplane of Solanum lycopersicum involves the establishment of complex molecular interaction between the microbe and the host including microbe-microbe interaction leading to an establishment of quorum sensing. The outcome will help in minimizing the HEP load on fresh farm produce, thereby curtailing incidences of food-borne diseases.

Keywords: crosslinkers, human enteric pathogens (HEPs), phylloplane, quorum sensing

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Authors: Ahmed Bahieldin, Ahmed Atef, Jamal S. M. Sabir, Nour O. Gadalla, Sherif Edris, Ahmed M. Alzohairy, Nezar A. Radhwan, Mohammed N. Baeshen, Ahmed M. Ramadan, Hala F. Eissa, Sabah M. Hassan, Nabih A. Baeshen, Osama Abuzinadah, Magdy A. Al-Kordy, Fotouh M. El-Domyati, Robert K. Jansen

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Wild salt-tolerant barley (Hordeum spontaneum) is the ancestor of cultivated barley (Hordeum vulgare or H. vulgare). Although the cultivated barley genome is well studied, little is known about genome structure and function of its wild ancestor. In the present study, RNA-Seq analysis was performed on young leaves of wild barley treated with salt (500 mM NaCl) at four different time intervals. Transcriptome sequencing yielded 103 to 115 million reads for all replicates of each treatment, corresponding to over 10 billion nucleotides per sample. Of the total reads, between 74.8 and 80.3% could be mapped and 77.4 to 81.7% of the transcripts were found in the H. vulgare unigene database (unigene-mapped). The unmapped wild barley reads for all treatments and replicates were assembled de novo and the resulting contigs were used as a new reference genome. This resultedin94.3 to 95.3%oftheunmapped reads mapping to the new reference. The number of differentially expressed transcripts was 9277, 3861 of which were uni gene-mapped. The annotated unigene- and de novo-mapped transcripts (5100) were utilized to generate expression clusters across time of salt stress treatment. Two-dimensional hierarchical clustering classified differential expression profiles into nine expression clusters, four of which were selected for further analysis. Differentially expressed transcripts were assigned to the main functional categories. The most important groups were ‘response to external stimulus’ and ‘electron-carrier activity’. Highly expressed transcripts are involved in several biological processes, including electron transport and exchanger mechanisms, flavonoid biosynthesis, reactive oxygen species (ROS) scavenging, ethylene production, signaling network and protein refolding. The comparisons demonstrated that mRNA-Seq is an efficient method for the analysis of differentially expressed genes and biological processes under salt stress.

Keywords: electron transport, flavonoid biosynthesis, reactive oxygen species, rnaseq

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Authors: Hosein Maghsoudi

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Rheumatois arthritis (RA) is progressive inflammatory autoimmune diseases that primarily affect the joints, characterized by synovial hyperplasia and inflammatory cell infiltration, deformed and painful joints, which can lead tissue destruction, functional disability systemic complications, and early dead and socioeconomic costs. The cause of rheumatoid arthritis is unknown, but genetic and environmental factors are contributory and the prognosis is guarded. However, advances in understanding the pathogenesis of the disease have fostered the development of new therapeutics, with improved outcomes. The current treatment strategy, which reflects this progress, is to initiate aggressive therapy soon after diagnosis and to escalate the therapy, guided by an assessment of disease activity, in pursuit of clinical remission. The pathobiology of RA is multifaceted and involves T cells, B cells, fibroblast-like synoviocyte (FLSc) and the complex interaction of many pro-inflammatory cytokine. Novel biologic agents that target tumor necrosis or interlukin (IL)-1 and Il-6, in addition T- and B-cells inhibitors, have resulted in favorable clinical outcomes in patients with RA. Despite this, at least 30% of RA patients are résistance to available therapies, suggesting novel mediators should be identified that can target other disease-specific pathway or cell lineage. Among the inflammatory cell population that might participated in RA pathogenesis, FLSc are crucial in initiaing and driving RA in concert of cartilage and bone by secreting metalloproteinase (MMPs) into the synovial fluid and by direct invasion into extracellular matrix (ECM), further exacerbating joint damage. Invasion of fibroblast-like synoviocytes (FLSc) is critical in the pathogenesis of rheumatoid-arthritis. The metalloproteinase (MMPs) and activator of Toll-like receptor 4 (TLR4)/nuclear factor- κB pthway play a critical role in RA-FLS invasion induced by lipopolysaccharide (LPS). The present study aimed to explore the anti-invasion activity of Glycyrrhizic Acid as a pharmacologically safe phytochemical agent with potent anti-inflammatory properties on IL-1beta and TNF-alpha signalling pathways in Bovine fibroblast-like synoviocyte ex- vitro, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Results showed that Glycyrrhizic Acid suppressed LPS-stimulated bovine FLS migration and invasion by inhibition MMP-9 expression and activity. In addition our results revealed that Glycyrrhizic Acid inhibited the transcriptional activity of MMP-9 by suppression the nbinding activity of NF- κB in the MMP-9 promoter pathway. The extract of licorice (Glycyrrhiza glabra L.) has been widely used for many centuries in the traditional Chinese medicine as native anti-allergic agent. Glycyrrhizin (GL), a triterpenoidsaponin, extracted from the roots of licorice is the most effective compound for inflammation and allergic diseases in human body. The biological and pharmacological studies revealed that GL possesses many pharmacological effects, such as anti-inflammatory, anti-viral and liver protective effects, and the biological effects, such as induction of cytokines (interferon-γ and IL-12), chemokines as well as extrathymic T and anti-type 2 T cells. GL is known in the traditional Chinese medicine for its anti-inflammatory effect, which is originally described by Finney in 1959. The mechanism of the GL-induced anti-inflammatory effect is based on different pathways of the GL-induced selective inhibition of the prostaglandin E2 production, the CK-II- mediated activation of both GL-binding lipoxygenas (gbLOX; 17) and PLA2, an anti-thrombin action of GL and production of the reactive oxygen species (ROS; GL exerts liver protection properties by inhibiting PLA2 or by the hydroxyl radical trapping action, leading to the lowering of serum alanine and aspartate transaminase levels. The present study was undertaken to examine the possible mechanism of anti-inflammatory properties GL on IL-1beta and TNF-alpha signalling pathways in bovine fibroblast-like synoviocyte ex-vivo, on LPS-stimulated bovine FLS migration and invasion as well as MMP expression and explored the upstream signal transduction. Our results clearly showed that treatment of bovine fibroblast-like synoviocyte with GL suppressed LPS-induced cell migration and invasion. Furthermore, it revealed that GL inhibited the transcription activity of MMP-9 by suppressing the binding activity of NF-κB in the MM-9 promoter. MMP-9 is an important ECM-degrading enzyme and overexpression of MMPs in important of RA-FLSs. LPS can stimulate bovine FLS to secret MMPs, and this induction is regulated at the transcription and translational levels. In this study, LPS treatment of bovine FLS caused an increase in MMP-2 and MMP-9 levels. The increase in MMP-9 expression and secretion was inhibited by ex- vitro. Furthermore, these effects were mimicked by MMP-9 siRNA. These result therefore indicate the the inhibition of LPS-induced bovine FLS invasion by GL occurs primarily by inhibiting MMP-9 expression and activity. Next we analyzed the functional significance of NF-κB transcription of MMP-9 activation in Bovine FLSs. Results from EMSA showed that GL suppressed LPS-induced NF-κB binding to the MMP-9 promotor, as NF-κB regulates transcriptional activation of multiple inflammatory cytokines, we predicted that GL might target NF-κB to suppress MMP-9 transcription by LPS. Myeloid differentiation-factor 88 (MyD88) and TIR-domain containing adaptor protein (TIRAP) are critical proteins in the LPS-induced NF-κB and apoptotic signaling pathways, GL inhibited the expression of TLR4 and MYD88. These results demonstrated that GL suppress LPS-induced MMP-9 expression through the inhibition of the induced TLR4/NFκB signaling pathway. Taken together, our results provide evidence that GL exerts anti-inflammatory effects by inhibition LPS-induced bovine FLSs migration and invasion, and the mechanisms may involve the suppression of TLR4/NFκB –mediated MMP-9 expression. Although further work is needed to clarify the complicated mechanism of GL-induced anti-invasion of bovine FLSs, GL might be used as a further anti-invasion drug with therapeutic efficacy in the treatment of immune-mediated inflammatory disease such as RA.

Keywords: glycyrrhizic acid, bovine fibroblast-like synoviocyte, tlr4/nf-κb, metalloproteinase-9

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Authors: Daniela E. Marin, Cornelia Braicu, Gina C. Pistol, Roxana Cojocneanu-Petric, Ioana Berindan Neagoe, Mihail A. Gras, Ionelia Taranu

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Aristolochic acid (AA) is a carcinogenic, mutagenic, and nephrotoxic compound commonly found in the Aristolochiaceae family of plants. AA is frequently associated with urothelial carcinoma of the upper urinary tract in human and animals and is considered as being responsible for Balkan Endemic Nephropathy. The pig provides a good animal model because the porcine urological system is very similar to that of humans, both in aspects of physiology and anatomy. MicroRNA (miRNA) are small non-coding RNAs that have an impact on a wide range of biological processes by regulating gene expression at post-transcriptional level. The objective of this study was to analyze the miRNA profiling in the kidneys of AA intoxicated swine. For this purpose, ten TOPIGS-40 crossbred weaned piglets, 4-week-old, male and females with an initial average body weight of 9.83 ± 0.5 kg were studied for 28 days. They were given ad libitum access to water and feed and randomly allotted to one of the following groups: control group (C) or aristolochic acid group (AA). They were fed a maize-soybean-meal-based diet contaminated or not with 0.25mgAA/kg. To profile miRNA in the kidneys of pigs, microarrays and bioinformatics approaches were applied to analyze the miRNA in the kidney of control and AA intoxicated pigs. After normalization, our results have shown that a total of 5 known miRNAs and 4 novel miRNAs had different profiling in the kidney of intoxicated animals versus control ones. Expression of miR-32-5p, miR-497-5p, miR-423-3p, miR-218-5p, miR-128-3p were up-regulated by 0.25mgAA/kg feed, while the expression of miR-9793-5p, miR-9835-3p, miR-9840-3p, miR-4334-5p was down-regulated. The microRNA profiling in kidney of intoxicated animals was associated with modified expression of target genes as: RICTOR, LASP1, SFRP2, DKK2, BMI1, RAF1, IGF1R, MAP2K1, WEE1, HDGF, BCL2, EIF4E etc, involved in cell division cycle, apoptosis, cell differentiation and cell migration, cell signaling, cancer etc. In conclusion, this study provides new data concerning the microRNA profiling in kidney after aristolochic acid intoxications with important implications for human and animal health.

Keywords: aristolochic acid, kidney, microRNA, swine

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Authors: Oluyomi Stephen Adeyemi, Kentaro Kato

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Toxoplasma gondii is the etiological agent of toxoplasmosis, a common parasitic disease capable of infecting a range of hosts, including nearly one-third of the human population. Current treatment options for toxoplasmosis patients are limited. In consequence, toxoplasmosis represents a large global burden that is further enhanced by the shortcomings of the current therapeutic options. These factors underscore the need for better anti-T. gondii agents and/or new treatment approach. In the present study, we sought to find out whether preparing and capping nanoparticles (NPs) in amino acids, would enhance specificity toward the parasite versus the host cell. The selection of amino acids was premised on the fact that T. gondii is auxotrophic for some amino acids. The amino acid-nanoparticles (amino-NPs) were synthesized, purified and characterized following established protocols. Next, we tested to determine the anti-T. gondii activity of the amino-NPs using in vitro experimental model of infection. Overall, our data show evidence that supports enhanced and excellent selective action against the parasite versus the host cells by amino-NPs. The findings are promising and provide additional support that warrants exploring the prospects of NPs as alternative anti-parasite agents. In addition, the anti-parasite action by amino-NPs indicates that nutritional requirement of parasite may represent a viable target in the development of better alternative anti-parasite agents. Furthermore, data suggest the anti-parasite mechanism of the amino-NPs involves multiple cellular processes including the production of reactive oxygen species (ROS), modulation of hypoxia-inducing factor-1 alpha (HIF-1α) as well as the activation of kynurenine pathway. Taken together, findings highlight further, the prospects of NPs as alternative source of anti-parasite agents.

Keywords: drug discovery, infectious diseases, mode of action, nanomedicine

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Authors: Giannis Arnaoutis, Dimitra Efthymiopoulou, Maria-Foivi Nikolopoulou, Yannis Manios

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AIM: Nitrate-containing supplements have been used extensively as ergogenic in many sports. However, extract fractions from plant-based nutritional sources high in nitrate and their effect on athletic performance, has not been systematically investigated. The purpose of the present study was to examine the possible effect of acute consumption of a “smart mixture” from beetroot and rocket on exercise capacity. MATERIAL & METHODS: 12 healthy, nonsmoking, recreationally active, males (age: 25±4 years, % fat: 15.5±5.7, Fat Free Mass: 65.8±5.6 kg, VO2 max: 45.46.1 mL . kg -1 . min -1) participated in a double-blind, placebo-controlled trial study, in a randomized and counterbalanced order. Eligibility criteria for participation in this study included normal physical examination, and absence of any metabolic, cardiovascular, or renal disease. All participants completed a time to exhaustion cycling test at 75% of their maximum power output, twice. The subjects consumed either capsules containing 360 mg of nitrate in total or placebo capsules, in the morning, under fasted state. After 3h of passive recovery the performance test followed. Blood samples were collected upon arrival of the participants and 3 hours after the consumption of the corresponding capsules. Time until exhaustion, pre- and post-test lactate concentrations, and rate of perceived exertion for the same time points were assessed. RESULTS: Paired-sample t-test analysis found a significant difference in time to exhaustion between the trial with the nitrate consumption versus placebo [16.1±3.0 Vs 13.5±2.6 min, p=0.04] respectively. No significant differences were observed for the concentrations of lactic acid as well as for the values in the Borg scale between the two trials (p>0.05). CONCLUSIONS: Based on the results of the present study, it appears that a nutritional supplement derived from vegetable extracts rich in nitrate, improves athletic performance in recreationally active young males. However, the precise mechanism is not clear and future studies are needed. Acknowledgment: This research has been co‐financed by the European Regional Development Fund of the European Union and Greek national funds through the Operational Program Competitiveness, Entrepreneurship and Innovation, under the call RESEARCH – CREATE – INNOVATE (project code:T2EDK-00843).

Keywords: sports performance, ergogenic supplements, nitrate, extract fractions

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Authors: Ahmad Zulfahmi Mohd Kamaruzaman, Mohd Ismail Ibrahim, Ariffin Marzuki Mokhtar, Maizun Mohd Zain, Saiful Nazri Satiman, Mohd Najib Majdi Yaacob

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Background: Aftermath any patient safety incidents, the involved healthcare providers possibly sustained second victim-related distress (second victim distress and reduced their professional efficacy), with subsequent negative work-related outcomes or vice versa cultivating resilience. This study aimed to investigate the factors affecting negative work-related outcomes and resilience, with the triad of support; colleague, supervisor, and institutional support as the hypothetical mediators. Methods: This was a cross sectional study recruiting a total of 733 healthcare providers from three tertiary care in Kelantan, Malaysia. Three steps of hierarchical linear regression were developed for each outcome; negative work-related outcomes and resilience. Then, four multiple mediator models of support triad were analyzed. Results: Second victim distress, professional efficacy, and the support triad contributed significantly for each regression model. In the pathway of professional efficacy on each negative work-related outcomes and resilience, colleague support partially mediated the relationship. As for second victim distress on negative work related outcomes, colleague and supervisor support were the partial mediator, and on resilience; all support triad also produced a similar effect. Conclusion: Second victim distress, professional efficacy, and the support triad influenced the relationship with the negative work-related outcomes and resilience. Support triad as the mediators ameliorated the effect in between and explained the urgency of having good support for recovery post encountering patient safety incidents.

Keywords: second victims, patient safety incidents, hierarchical linear regression, mediation, support

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Authors: Ying Sun, Biao Cheng, Qing Lu, Xuefei Tao, Xiaoyu Lai, Cheng Guo, Dan Wang

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Fibrinogen-like protein 2 (FGL2) has recently been identified to play an important role in inflammatory diseases such as atherosclerosis through a thrombin-dependent manner. Here, a murine monoclonal antibody was raised against the critical residue Ser(89) of FGL2, and the effects of the anti-FGL2 mAb (SPF89) were analyzed in human umbilical vein endothelial cells (HUVECs) and THP-1 cells. Firstly, it was proved that SPF89, which belongs to the IgG1 subtype with a KD value of 44.5 pM, could specifically show the expression levels of protein FGL2 in different cell lines of known target gene status. The lipopolysaccharide (LPS)-mediated endothelial cell proliferation was significantly inhibited with a decline of phosphorylation nuclear factor-κB (NF-κB) in a dose-dependent manner after SPF89 treatment. Furthermore, SPF89 reduced LPS-induced expression of adhesion molecules and inflammatory cytokines such as vascular cell adhesion molecule-1, tumor necrosis factor-α, Matrix metalloproteinase MMP-2, Integrin αvβ3, and interleukin-6 in HUVECs. In macrophage-like THP-1 cells, SPF89 effectively inhibited LPS and low-density lipoprotein-induced foam cell formation. However, these anti-inflammatory and anti-atherosclerotic effects of anti-FGL2 mAb in HUVECs and THP-1 cells were significantly reduced after treatment with an NF-κB inhibitor PDTC. All the above suggest, by efficiently inhibiting LPS-induced pro-inflammatory effects in vascular endothelial cells by attenuating NF-κB dependent pathway, the new anti-FGL2 mAb SPF89 could to be a potential therapeutic candidate for protecting the vascular endothelium against inflammatory diseases such as atherosclerosis. This work was supported by the Program of Sichuan Science and Technology Department (2017FZ0069) and Collaborative Innovation Program of Sichuan for Elderly Care and Health(YLZBZ1511).

Keywords: monoclonal antibody, fibrinogen like protein 2, inflammation, endothelial cells

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Authors: Kristine Joy Y. Sumanga, Clarissa Mae D. Derecho

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Telemedicine is providing health care services using electronic means at a distance, including the diagnosis, treatment, and prevention of diseases as well as the research and evaluation and education of health care providers. The role of telemedicine in this time of the COVID-19 pandemic is vital, especially in the practice of medicine. General Objective: To determine the extent of knowledge, preparedness and perception of telemedicine among Family Medicine Resident Physicians in different training institutions in Cebu City during the Coronavirus Disease 19 pandemic. Methods: A descriptive, cross-sectional survey research study was conducted in four hospital training institutions in Cebu City. A total of 41 respondents gave their consent and were given the online survey questionnaire pertaining to the extent of knowledge, preparedness and perceptions on telemedicine, including respondents’ demographic data and problems encountered in Telemedicine. Results: Out of the 41 respondents, 56.10% were young adults (26 to 30 years old), mostly females (70.73%), single (68.29%), first-year residents (43.90%), employed at a government hospital (70.73%) and are in the traditional residency pathway (82.93%). On relevant experience, 82.93% experienced telemedicine during residency, with 100% on follow-up consultations, and 95% were consulted due to infections. Respondents’ extent of knowledge was average, while the extent of preparedness and perception were great. Problems with low connectivity (80.48%) were noted by most of the respondents. Conclusion: Resident physicians moderately understood the information about telemedicine but with a great extent of preparedness and perception. They are always prepared for telemedicine modality because they are fully aware of its existence and need in the delivery of health care services among their patients at the time of the pandemic. Challenges to low connectivity and handling patients’ data privacy were the major concerns met by the resident physicians in the use of telemedicine.

Keywords: telemedicine, knowledge, preparedness, perception, family medicine, residents, COVID 19

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Authors: Ruchi Jain, Chinnakonda S. Gopinath

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The CO oxidation is a primary reaction in heterogeneous catalysis due to its potential to overcome the air pollution caused by various reasons. Indeed, in the study of sustainable catalysis, the role played by water is very important. The present work is focused on studying the effect of moisture on the sustainability of Co3O4 NR catalyst for CO oxidation reaction at ambient temperature. The catalytic activity, electronic structure and the mechanistic aspects of spinel Co3O4 nanorod surfaces have been explored in dry and wet atmosphere by near-ambient pressure photoelectron spectroscopic techniques (NAP-PES) with conventional x-ray (Al kα) and ultraviolet sources (He-I).Comparative NAPPES studies have been employed to understand the elucidation of the catalytic reaction pathway and the evolution of various surface species. The presence of water with CO+O2 plummet the catalytic activity due to the change in electronic nature from predominantly oxidic (without water in the feed) to few intermediates covered Co3O4 surface. However, ≥ 375 K Co3O4 surface recovers and regain oxidation activity, at least partially, even in the presence of water. Above mentioned observations are fully supported by the changes observed in the work function of Co3O4 in the presence of wet (H2O+CO+O2) compared to dry (CO+O2) conditions. Various type of surface species, such as CO(ads), carbonate, formate, are found to be on the catalyst surface depending on the reaction conditions. Under dry condition, CO couples with labile O atoms to form CO2, however under wet conditions it also interacts with surface OH groups results in the formation carbonate and formate intermediate. The carbonate acts at reaction inhibitor at room temperature, however proves as active intermediate at temperature 375 K or above. On the other hand, formate has proved to be reaction spectator due to its high stability. The intrinsic role of these species to suppress the oxidation has been demonstrated through a possible reaction mechanism under different reaction conditions.

Keywords: heterogeneous catalysis, surface chemistry, photoelectron spectroscopy, ambient oxidation

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Authors: Madeleine Elder, Aye Htun

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Background: Myiasis is the parasitic infestation of body tissues by fly larvae. It predominantly occurs in poor socioeconomic regions of tropical and subtropical countries where it is associated with poor hygiene and sanitation. Cutaneous and wound myiasis are the most common presentations whereas urogenital myiasis is rare, with few reported cases. Case: a 26-year-old primiparous woman with a low-risk pregnancy presented to the emergency department at 37+3-weeks’ gestation after passing a 2cm black larva during micturition, with 2 weeks of mild vulvar pruritus and dysuria. She had travelled to India 9-months prior. Examination of the external genitalia showed small white larvae over the vulva and anus and a mildly inflamed introitus. Speculum examination showed infiltration into the vagina and heavy white discharge. High vaginal swab reported Candida albicans. Urine microscopy reported bacteriuria with Enterobacter cloacae. Urine parasite examination showed myiasis caused by Clogmia albipunctata species of fly larvae from the family Psychodidae. Renal tract ultrasound and inflammatory markers were normal. Infectious diseases, urology and paediatric teams were consulted. The woman received treatment for her urinary tract infection (which was likely precipitated by bladder irritation from local parasite infestation) and vaginal candidiasis. She underwent daily physical removal of parasites with cleaning, speculum examination and removal, and hydration to promote bladder emptying. Due to the risk of neonatal exposure, aspiration pneumonitis and facial infestation, the woman was steroid covered and proceeded to have an elective caesarean section at 38+3-weeks’ gestation, with delivery of a healthy infant. She then proceeded to have a rigid cystoscopy and washout, which was unremarkable. Placenta histopathology revealed focal eosinophilia in keeping with the history of maternal parasites. Conclusion: Urogenital myiasis is very rare, especially in the developed world where it is seen in returned travellers. Treatment may include systemic therapy with ivermectin and physical removal of parasites. During pregnancy, physical removal is considered the safest treatment option, and discussion around the timing and mode of delivery should consider the risk of harm to the foetus.

Keywords: urogenital myiasis, parasitic infection, infection in pregnancy, returned traveller

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Authors: Misha Nedeljkovich

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In the film’s famous scene (Roma città aperta-1945), Pina (Anna Magnani) collapses in the street when machined-gunned by a German soldier. Her son Marcello (Vito Annchiarico) tries to revive her. Her death is signaling not closure, but the cycle of life; Marcello saves Francesco with the shawl taken from his mother’s corpse. One pivotal scene in Brief Encounter (1945) occurs in the apartment of Alec’s (Trevor Howard) friend Stephen (Valentine Dyall), when Stephen returns to catch Alec and Laura (Celia Johnson) together alone. David Lean directs this scene using her shawl as a sign of in flagrante delicto. In La Strada (1954), Gelsomina (Giulietta Masina) was waving good bye when her mother sensing impending doom changed her mind and desperately tried to stop her waving back with her shawl: Don’t go my daughter! Your shawl! Your shawl! Gelsomina refuses to return, waving back: It’s time to go! Stanley Kubrick’s tale of a boxer who crosses a mobster to win the heart of a lady, Killer’s Kiss (1955), reminds us that Times Square used to contain sweaty boxing gyms and dance halls. The film’s longest Times Square interlude is its oddest: the boxer Davie Gordon played by Jamie Smith has his shawl stolen by two playful men in Shriners’ hats who are silent except for one who blows a harmonica, faintly heard over honking cabs and overheard conversations. This long sequence appears to be joining in on directors’ shawl conversations with Kubrick’s own twist. Principle characters will never know why all this happened to them that evening. Love, death, happiness and everlasting misery all of that is caused by Dave’s shawl. Finally, the decade of cinematic shawl conversations conclude in Betolucci’s Before the Revolution (Prima della rivoluzione–1964). One of his character’s lifts up a shawl asking if this was a Rossellini’s shawl. I argue that exploring complimentary allusions in a film where directors are acknowledging their own great debt to another film or filmmaker will further our knowledge of film history adding both depth and resonance to the great works in cinema.

Keywords: allusions, Bertolucci, Fellini, homage, Kubrick, lean, Rossellini

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Authors: Somayeh Khanjani, Samaneh Nabavi, Shirin Jalili

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Aluminum phosphide (ALP) is an inorganic phosphide used to control insects and is a highly effective insecticide and rodenticide used frequently to protect stored grain. Acute poisoning with this compound is common in some countries including India and Iran, and is a serious health problem. In Iran it was known as "rice tablet", for its use to preserve rice. Two kinds of rice tablets one being herbal while other containing 3g aluminum phosphide (AlP) are available for use in Iranian households to protect stored food grains from pests and rodents. The toxicity of Aluminum phosphide is attributed to the liberation of phosphine gas in contact with water or weak acid and is the major cause of poisoning and deaths. Rice tablet (Aluminum Phosphid) poisoning may be associated with serious and sometimes incurable complications. In 61.3% of patients were shown uniform ingestion. Vomiting was the most common symptoms reported by 96.4% patients. Agitation was reported in 36.9% and felling of thirsty in 27.9 %. Although many complications such as Hypotension, Adult Respiratory Distress Syndrome (ARDS), Acute Renal Failure (ARF) AND Multi Organ Failure (MOF) were the common complications observed in these patients, but the most lethal complication was Cardiac Arrhythmias occurred in 36.9% of cases. Abdominal pain in 31.4% of the patients, nausea in 79.4% of the patients and 41.1% of the patients showed metabolic acidosis. Suicidal intention was the most common cause of poisoning leading to deaths in 18.6% of the patients. Aluminum phosphide can cause either elevation, decrease or no change in electrolytes, bicarbonate and blood glucose level. The possible mechanism for changes in blood glucose levels are complex and depend on the balance of factors which increase its concentration and those which reduce it. AlP poisoning has been postulated to stimulate cortisol which leads to increasing blood level of cortisol, also it may cause stimulation of glucagon, and Adrenaline secretion; in addition, it can inhibit insulin synthesis which may lead to hyperglycemia. Another suggested mechanism of hyperglycemia is rennin activity in some cases, an increase in magnesium level of plasma and that of tissues, and high phosphate level. Although hyperglycemia is most frequent in this poisoning and also is known as a marker of poor prognostic, hypoglycemia in aluminum phosphide poisoning is a rare finding which may be so dangerous. Patients showed sever hypotension and sever acidosis in addition to sever hypoglycemia. The presenting features of AlP intoxication are rapid onset of shock, severe metabolic acidosis, cardiac dysrhythmias and adult respiratory distress syndrome (ARDS).

Keywords: aluminum phosphide (ALP), rice tablet, poisoning, phosphine gas

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Authors: Jia-Ling Ho, Xiu-Ru Zhang, Zwe-Ling Kong

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Diabetes mellitus (DM) is a major health problem that affects patients’ life quality throughout the world due to its many complications. It characterized by chronic hyperglycemia with oxidative stress, which impaired male reproductive function. Fibroblast growth factor 21 (FGF21) is a metabolic regulator that is required for normal spermatogenesis and protects against diabetes-induced germ cell apoptosis. Echinacea purpurea ethanol extract (EE), which contain phenolic acid and isobutylamide, had been proven to have antidiabetic property. Silica-chitosan nanoparticles (Nano-CS) has drug delivery and controlled release properties. This study aims to investigate whether silica-chitosan nanoparticles encapsulated EE (Nano-EE) had more ameliorating male infertility by analyzing the effect of testicular FGF21. The Nano-EE was characterized before used to treatment the diabetic rat model. Male Sprague-Dawley (SD) rats were obtained and divided into seven groups. A group was no induced Streptozotocin (STZ), marked as normal group. Diabetic rats were induced into diabetes by STZ (33 mg/kg). A diabetic group was no treatment with sample (diabetic control group), and other groups were treatment by Nano-CS (465 mg/kg), Nano-EE (93, 279, 465 mg/kg), and metformin (Met) (200 mg/kg) used as reference drug for 7 weeks. Our results indicated that the average nanoparticle size and zeta potential of Nano-EE were 2630 nm and -21.3 mV, respectively. The encapsulation ratio of Nano-EE was about 70%. It also confirmed the antioxidative activity was unchanged by comparing the DPPH and ABTS scavenging of Nano-EE and EE. In vivo test, Nano-EE can improve the STZ induced hyperglycemia, insulin resistance, and plasma FGF21 levels. Nano-EE has increased sperm motility, mitochondria membrane potential (MMP), plasma testosterone level, and reduction of abnormal sperm, nitric oxide (NO), superoxide production as well as reactive oxygen species (ROS). In addition, in plasma antioxidant enzymes glutathione peroxidase (GPx) and superoxide dismutase (SOD) was increased whereas pro-inflammatory cytokines TNF-α, and IL-1β were decreased. Further, in testis, protein content of FGF21, PGC-1α, and SIRT1 were improved. Nano-EE might improve diabetes-induced down-regulation of testicular FGF21 and SIRT1/PGC-1α signaling hence maintain spermatogenesis.

Keywords: diabetes mellitus, Echinacea purpurea, reproductive dysfunction, silica-chitosan nanoparticles

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Authors: Tais Basaco, Stefanie Pektor, Josue A. Moreno, Matthias Miederer, Andreas Türler

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Radiopharmaceuticals based in monoclonal anti-body (mAb) via chemical linkers have become a potential tool in nuclear medicine because of their specificity and the large variability and availability of therapeutic radiometals. It is important to identify the conjugation sites and number of attached chelator to mAb to obtain radioimmunoconjugates with required immunoreactivity and radiostability. Girentuximab antibody (G250) is a potential candidate for radioimmunotherapy of clear cell carcinomas (RCCs) because it is reactive with CAIX antigen, a transmembrane glycoprotein overexpressed on the cell surface of most ( > 90%) (RCCs). G250 was conjugated with the bifunctional chelating agent DOTA (1,4,7,10-Tetraazacyclododecane-N,N’,N’’,N’’’-tetraacetic acid) via a benzyl-thiocyano group as a linker (p-SCN-Bn-DOTA). DOTA-G250 conjugates were analyzed by size exclusion chromatography (SE-HPLC) and by electrophoresis (SDS-PAGE). The potential site-specific conjugation was identified by liquid chromatography–mass spectrometry (LC/MS-MS) and the number of linkers per molecule of mAb was calculated using the molecular weight (MW) measured by matrix assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOF MS). The average number obtained in the conjugates in non-reduced conditions was between 8-10 molecules of DOTA per molecule of mAb. The average number obtained in the conjugates in reduced conditions was between 1-2 and 3-4 molecules of DOTA per molecule of mAb in the light chain (LC) and heavy chain (HC) respectively. Potential DOTA modification sites of the chelator were identified in lysine residues. The biological activity of the conjugates was evaluated by flow cytometry (FACS) using CAIX negative (SKRC-18) and CAIX positive (SKRC-52). The DOTA-G250 conjugates were labelled with 177Lu with a radiochemical yield > 95% reaching specific activities of 12 MBq/µg. The stability in vitro of different types of radioconstructs was analyzed in human serum albumin (HSA). The radiostability of 177Lu-DOTA-G250 at high specific activity was increased by addition of sodium ascorbate after the labelling. The immunoreactivity was evaluated in vitro and in vivo. Binding to CAIX positive cells (SK-RC-52) at different specific activities was higher for conjugates with less DOTA content. Protein dose was optimized in mice with subcutaneously growing SK-RC-52 tumors using different amounts of 177Lu- DOTA-G250.

Keywords: mass spectrometry, monoclonal antibody, radiopharmaceuticals, radioimmunotheray, renal cancer

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Authors: Gabriele Ciasca, Tanya E. Sassun, Eleonora Minelli, Manila Antonelli, Massimiliano Papi, Antonio Santoro, Felice Giangaspero, Roberto Delfini, Marco De Spirito

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Glioblastoma multiforme (GBM) is an extremely aggressive brain tumor, characterized by a diffuse infiltration of neoplastic cells into the brain parenchyma. Although rarely considered, mechanical cues play a key role in the infiltration process that is extensively mediated by the tumor microenvironment stiffness and, more in general, by the occurrence of aberrant interactions between neoplastic cells and the extracellular matrix (ECM). Here we provide a nano-mechanical characterization of the viscoelastic response of human GBM tissues by indentation-type atomic force microscopy. High-resolution elasticity maps show a large difference between the biomechanics of GBM tissues and the healthy peritumoral regions, opening possibilities to optimize the tumor resection area. Moreover, we unveil the nanomechanical signature of necrotic regions and anomalous vasculature, that are two major hallmarks useful for glioma staging. Actually, the morphological grading of GBM relies mainly on histopathological findings that make extensive use of qualitative parameters. Our findings have the potential to positively impact on the development of novel quantitative methods to assess the tumor grade, which can be used in combination with conventional histopathological examinations. In order to provide a more in-depth description of the role of mechanical cues in tumor progression, we compared the nano-mechanical fingerprint of GBM tissues with that of grade-I (WHO) meningioma, a benign lesion characterized by a completely different growth pathway with the respect to GBM, that, in turn hints at a completely different role of the biomechanical interactions.

Keywords: AFM, nano-mechanics, nanomedicine, brain tumors, glioblastoma

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Authors: Saad Al-Shibli, Nasser Amjad, Muna Al Kubaisi, Norra Harun, Shaikh Mizan

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Leptin is a multifunctional hormone produced mainly by adipocyte. Leptin and its receptor have long been found associated with breast cancer. The main aim of this study is to investigate the correlation between Leptin/Leptin receptor and the clinicopathological features of breast cancer. Blood samples for ELISA, tissue samples from tumors and adjacent breast tissue were taken from 51 women with breast cancer with a control group of 40 women with a negative mammogram. Leptin and Leptin receptor in the tissues were estimated by immunohistochemistry (IHC). They were localized at the subcellular level by immunocytochemistry using transmission electron microscopy (TEM). Our results showed significant difference in serum leptin level between control and the patient group, but no difference between pre and post-operative serum leptin levels in the patient group. By IHC, we found that the majority of the breast cancer cells studied, stained positively for leptin and leptin receptors with co-expression of leptin and its receptors. No significant correlation was found between leptin/leptin receptors expression with the race, menopausal status, lymph node metastasis, estrogen receptor expression, progesterone receptor expression, HER2 expression and tumor size. Majority of the patients with distant metastasis were associated with high leptin and leptin receptor expression. TEM views both Leptin and Leptin receptor were found highly concentrated within and around the nucleus of the cancer breast cells, indicating nucleus is their principal seat of actions while the adjacent breast epithelial cells showed that leptin gold particles are scattered all over the cell with much less than that of the cancerous cells. However, presence of high concentration of leptin does not necessarily prove its over-expression, because it could be internalized from outside by leptin receptor in the cells. In contrast, leptin receptor is definitely over-expressed in the ductal breast cancer cells. We conclude that reducing leptin levels, blocking its downstream tissue specific signal transduction, and/or blocking the upstream leptin receptor pathway might help in prevention and therapy of breast cancer.

Keywords: breast cancer, expression, leptin, leptin receptors

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