Search results for: myostatin signaling pathway

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: 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: 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: 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: 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: 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: Parisa Mansour

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Understanding how vision works in both health and disease involves understanding the anatomy and physiology of the eye as well as the neural pathways involved in visual perception. The development of imaging techniques for the visual system is essential for understanding the neural foundation of visual function or impairment. MRI provides a way to examine neural circuit structure and function without invasive procedures, allowing for the detection of brain tissue abnormalities in real time. One of the advanced MRI methods is manganese-enhanced MRI (MEMRI), which utilizes active manganese contrast agents to enhance brain tissue signals in T1-weighted imaging, showcasing connectivity and activity levels. The way manganese ions build up in the eye, and visual pathways can be due to their spread throughout the body or by moving locally along axons in a forward direction and entering neurons through calcium channels that are voltage-gated. The paramagnetic manganese contrast is utilized in MRI for various applications in the visual system, such as imaging neurodevelopment and evaluating neurodegeneration, neuroplasticity, neuroprotection, and neuroregeneration. In this assessment, we outline four key areas of scientific research where MEMRI can play a crucial role - understanding brain structure, mapping nerve pathways, monitoring nerve cell function, and distinguishing between different types of glial cell activity. We discuss various studies that have utilized MEMRI to investigate the visual system, including delivery methods, spatiotemporal features, and biophysical analysis. Based on this literature, we have pinpointed key issues in the field related to toxicity, as well as sensitivity and specificity of manganese enhancement. We will also examine the drawbacks and other options to MEMRI that could offer new possibilities for future exploration.

Keywords: glial activity, manganese-enhanced magnetic resonance imaging, neuroarchitecture, neuronal activity, neuronal tract tracing, visual pathway, eye

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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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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: Mayada Mazher, Ahmed Moustafa, Ahmed Abdellatif

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Background: Autophagy is a eukaryotic, highly conserved catabolic process implicated in many pathophysiologies such as wound healing. Autophagy-associated genes serve as a scaffolding platform for signal transduction of macrophage polarization during the inflammatory phase of wound healing and tissue repair process. In the current study, we report a model for the interplay between autophagy-associated genes and macrophages polarization associated genes. Methods: In silico analysis was performed on 249 autophagy-related genes retrieved from the public autophagy database and gene expression data retrieved from Gene Expression Omnibus (GEO); GSE81922 and GSE69607 microarray data macrophages polarization 199 DEGS. An integrated protein-protein interaction network was constructed for autophagy and macrophage gene sets. The gene sets were then used for GO terms pathway enrichment analysis. Common transcription factors for autophagy and macrophages' polarization were identified. Finally, microRNAs enriched in both autophagy and macrophages were predicated. Results: In silico prediction of common transcription factors in DEGs macrophages and autophagy gene sets revealed a new role for the transcription factors, HOMEZ, GABPA, ELK1 and REL, that commonly regulate macrophages associated genes: IL6,IL1M, IL1B, NOS1, SOC3 and autophagy-related genes: Atg12, Rictor, Rb1cc1, Gaparab1, Atg16l1. Conclusions: Autophagy and macrophages' polarization are interdependent cellular processes, and both autophagy-related proteins and macrophages' polarization related proteins coordinate in tissue remodelling via transcription factors and microRNAs regulatory network. The current work highlights a potential new role for transcription factors HOMEZ, GABPA, ELK1 and REL in wound healing.

Keywords: autophagy related proteins, integrated network analysis, macrophages polarization M1 and M2, tissue remodelling

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Authors: Fanous Mohammadi, Majid H. Tangestani, Mohammad H. Tayebi

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This research aims to evaluate and compare Geographical Information Systems (GIS)-based fuzzy models for producing orogenic gold prospectivity maps in the Saqqez area, NW of Iran. Gold occurrences are hosted in sericite schist and mafic to felsic meta-volcanic rocks in this area and are associated with hydrothermal alterations that extend over ductile to brittle shear zones. The predictor maps, which represent the Pre-(Source/Trigger/Pathway), syn-(deposition/physical/chemical traps) and post-mineralization (preservation/distribution of indicator minerals) subsystems for gold mineralization, were generated using empirical understandings of the specifications of known orogenic gold deposits and gold mineral systems and were then pre-processed and integrated to produce mineral prospectivity maps. Five fuzzy logic operators, including AND, OR, Fuzzy Algebraic Product (FAP), Fuzzy Algebraic Sum (FAS), and GAMMA, were applied to the predictor maps in order to find the most efficient prediction model. Prediction-Area (P-A) plots and field observations were used to assess and evaluate the accuracy of prediction models. Mineral prospectivity maps generated by AND, OR, FAP, and FAS operators were inaccurate and, therefore, unable to pinpoint the exact location of discovered gold occurrences. The GAMMA operator, on the other hand, produced acceptable results and identified potentially economic target sites. The P-A plot revealed that 68 percent of known orogenic gold deposits are found in high and very high potential regions. The GAMMA operator was shown to be useful in predicting and defining cost-effective target sites for orogenic gold deposits, as well as optimizing mineral deposit exploitation.

Keywords: mineral prospectivity mapping, fuzzy logic, GIS, orogenic gold deposit, Saqqez, Iran

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Authors: Manish Khanra, Shashank Prabhu

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The decarbonization of hard-to-abate sectors is currently high on the agenda in the EU and its member states, as these sectors have substantial shares in overall GHG emissions while it is facing serious challenges to decarbonize. In particular, the aviation sector accounts for 2.8% of global anthropogenic CO₂ emissions. These emissions are anticipated to grow dramatically unless immediate mitigating efforts are implemented. Hydrogen and its derivatives based on renewable electricity can have a key role in the transition towards CO₂-neutral flights. The substantial shares of energy carriers in the form of drop-in fuel, direct combustion and Hydrogen-to-Electric are promising in most scenarios towards 2050. For creating appropriate policies to ramp up the production and utilisation of hydrogen commodities in the German aviation sector, a detailed analysis of the spatial distribution of supply-demand sites is essential. The objective of this research work is to assess the demand for hydrogen-based alternative fuels in the German aviation sector to achieve the perceived goal of the ‘Net Zero’ scenario by 2050. Here, the analysis of the technological pathways for the production and utilisation of these fuels in various aircraft options is conducted for reaching mitigation targets. Our method is based on data-driven bottom-up assessment, considering production and demand sites and their spatial distribution. The resulting energy demand and its spatial distribution with consideration of technology diffusion lead to a possible transition pathway of the aviation sector to meet short-term and long-term mitigation targets. Additionally, to achieve mitigation targets in this sector, costs and policy aspects are discussed, which would support decision-makers from airline industries, policymakers and the producers of energy commodities.

Keywords: the aviation sector, hard-to-abate sectors, hydrogen demand, alternative fuels, technological pathways, data-driven approach

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Authors: Ananya Govindarajan

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Tetrahymena thermophila is a single-cell, eukaryotic organism that belongs to the Protozoa Kingdom. Tetrahymena thermophila is often used in signal transduction pathway studies because of its ability to model sensory input and the effects of environmental conditions such as chemicals and temperature. The recently discovered G37 chemorepellent receptor showed increased responsiveness to all chemorepellents. Investigating the mutant G37 Tetrahymena gene in various test solutions, including ferric chloride, ferrous sulfate, hydrogen peroxide, tetrazolium blue, potassium chloride, and dithiothreitol were performed to determine the role of oxidants and reducing agents with the mutant and wild-type cells (CU427) to assess the role of the receptor. Behavioral assays and recordings processed by ImageJ indicated that ferric chloride, hydrogen peroxide, and tetrazolium blue yielded little to no chemorepellent responses from G37 cells (<20% ARs). CU427 cells were over-responsive based on the mean percent of cells (>50% ARs). Reducing agents elicited chemorepellent responses from both G37 and CU427, in addition to potassium chloride. Cell responses were classified as over-responsive (>50% ARs). Dithiothreitol yielded unexpected results as G37 (37.0% ARs) and CU427 (38.1% ARs) had relatively similar responses and were only responsive and not over-responsive to the reducing agent test chemical solution. Ultimately, this indicates that the G37 receptor is more interactive with molecules that are reducing agents or non-oxidant compounds; G37 may be unable to sense and respond to oxidants effectively, further elucidating the pathways of the G37 strain and nature of this receptor. Results also indicate that the CSF most likely contained an oxidant, like ferric chloride. This research can be further applied to neuronal influences and how specific compounds may affect human neurons individually and their excitability as the responses model action potentials and membrane potential.

Keywords: tetrahymena thermophila, signal transduction, chemosensory, oxidant, reducing agent

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Authors: Govinda Pathak

Abstract:

In modern agriculture, the sustainable enhancement of crop productivity while minimizing environmental impacts remains a paramount challenge. Plant Growth Promoting Rhizobacteria (PGPR) have emerged as a promising solution to address this challenge. The rhizosphere, the dynamic interface between plant roots and soil, hosts intricate microbial interactions crucial for plant health and nutrient acquisition. PGPR, a subset of rhizospheric microorganisms, exhibit multifaceted beneficial effects on plants. Their abilities to stimulate growth, confer stress tolerance, enhance nutrient availability, and suppress pathogens make them invaluable contributors to sustainable agriculture. This work examines the pivotal role of free living nitrogen fixer in optimizing agricultural practices. We delve into the intricate mechanisms underlying PGPR-mediated plant-microbe interactions, encompassing quorum sensing, root exudate modulation, and signaling molecule exchange. Furthermore, we explore the diverse strategies employed by PGPR to enhance plant resilience against abiotic stresses such as drought, salinity, and metal toxicity. Additionally, we highlight the role of PGPR in augmenting nutrient acquisition and soil fertility through mechanisms such as nitrogen fixation, phosphorus solubilization, and mineral mobilization. Furthermore, we discuss the potential of PGPR in minimizing the reliance on chemical fertilizers and pesticides, thereby contributing to environmentally friendly agriculture. However, harnessing the full potential of PGPR requires a comprehensive understanding of their interactions with host plants and the surrounding microbial community. We also address challenges associated with PGPR application, including formulation, compatibility, and field efficacy. As the quest for sustainable agriculture intensifies, harnessing the remarkable attributes of PGPR offers a holistic approach to propel agricultural productivity while maintaining ecological balance. This work underscores the promising prospect of free living nitrogen fixer as a panacea for addressing critical agricultural challenges regarding chemical urea in an era of sustainable and resilient food production.

Keywords: PGPR, nitrogen fixer, quorum sensing, Rhizobacteria, pesticides

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Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: copper oxide nanoparticles, green synthesis, nanotechnology, microbial infection

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Authors: Wafa Jahouach-Rabai, Khouloud Ouerghi, Zohra Azzouz-Berriche, Faouzi Hosni

Abstract:

Widely used organic products in the pharmaceutical industry have been detected in environmental systems, essentially carboxylic acids. In this purpose, the degradation efficiency of these contaminants was evaluated using an advanced oxidation process (AOP), namely ionization process as an alternative to conventional water treatment technologies. This process permitted the generation of radical reactions to directly degrade organic pollutants in wastewater. In fact, gamma irradiation of aqueous solutions produces several reactive radicals, essentially hydroxyl radical (OH), to destroy recalcitrant pollutants. Different concentrations of aqueous solutions of Fumaric acid (FA) were considered in this study (0.1-1 mmol/L), which were treated by irradiation doses from 1 to 15 kGy with 6.1 kGy/h rate by ionizing system in pilot scale (⁶⁰Co irradiator). Variations of main parameters influencing degradation efficiency versus absorbed doses were released in the aim to optimize total mineralization of considered pollutants. Preliminary degradation pathway until complete mineralization into CO₂ has been suggested based on detection of residual degradation derivatives using different techniques, namely high performance liquid chromatography (HPLC) and electron paramagnetic resonance spectroscopy (EPR). Results revealed total destruction of treated compound, which improve the efficiency of this process in water remediation. We investigated the reactivity of hydroxyl radicals generated by irradiation on dicarboxylic acid (FA) in aqueous solutions, leading to its degradation into other smaller molecules. In fact, gamma irradiation of FA leads to the formation of hydroxylated intermediates such as hydroxycarbonyl radical which were identified by EPR spectroscopy. Finally, pilot plant irradiation facilities improved the applicability of radiation technology on large scale.

Keywords: AOP, radiolysis, fumaric acid, gamma irradiation, hydroxyl radical, EPR, HPLC

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Authors: Brindusa Balanuca, Raluca Stan, Cristina Ott, Matei Raicopol

Abstract:

The current study aims to develop anti corrosive coatings using vegetable oil (VO)-based polymers. Due to their chemical versatility, reduced costs and more important, higher hydrophobicity, VO’s are great candidates in the field of anti-corrosive materials. Lignin (Ln) derivatives were also used in this research study in order to achieve performant hydrophobic anti-corrosion layers. Methods Through a rational functionalization pathway, the selected VO (linseed oil) is converted to more reactive monomer – methacrylate linseed oil (noted MLO). The synthesized MLO cover the metals surface in a thin layer and through different polymerization techniques (using visible radiation or temperature, respectively) and well-established reaction conditions, is converted to a hydrophobic coating capable to protect the metals against corrosive factors. In order to increase the anti-corrosion protection, lignin (Ln) was selected to be used together with MLO macromonomer. Thus, super hydrophobic protective coatings will be formulated. Results The selected synthetic strategy to convert the VO in more reactive compounds – MLO – has led to a functionalization degree of greater than 80%. The obtained monomers were characterized through NMR and FT-IR by monitoring the characteristic signals after each synthesis step. Using H-NMR data, the functionalization degrees were established. VO-based and also VO-Ln anti corrosion formulations were both photochemical and thermal polymerized in specific reaction conditions (initiators, temperature range, reaction time) and were tested as anticorrosive coatings. Complete and advances characterization of the synthesized materials will be presented in terms of thermal, mechanical and morphological properties. The anticorrosive properties were also evaluated and will be presented. Conclusions Through the design strategy briefly presented, new composite materials for metal corrosion protection were successfully developed, using natural derivatives: vegetable oils and lignin, respectively.

Keywords: anticorrosion protection, hydrophobe layers, lignin, methacrylates, vegetable oil

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Authors: Yemane Tadesse Gebreslassie, Fisseha Guesh Gebremeskel

Abstract:

Nanotechnology has made remarkable advancements in recent years, revolutionizing various scientific fields, industries, and research institutions through the utilization of metal and metal oxide nanoparticles. Among these nanoparticles, copper oxide nanoparticles (CuO NPs) have garnered significant attention due to their versatile properties and wide-range applications, particularly, as effective antimicrobial and anticancer agents. CuO NPs can be synthesized using different methods, including physical, chemical, and biological approaches. However, conventional chemical and physical approaches are expensive, resource-intensive, and involve the use of hazardous chemicals, which can pose risks to human health and the environment. In contrast, biological synthesis provides a sustainable and cost-effective alternative by eliminating chemical pollutants and allowing for the production of CuO NPs of tailored sizes and shapes. This comprehensive review focused on the green synthesis of CuO NPs using various biological resources, such as plants, microorganisms, and other biological derivatives. Current knowledge and recent trends in green synthesis methods for CuO NPs are discussed, with a specific emphasis on their biomedical applications, particularly in combating cancer and microbial infections. This review highlights the significant potential of CuO NPs in addressing these diseases. By capitalizing on the advantages of biological synthesis, such as environmental safety and the ability to customize nanoparticle characteristics, CuO NPs have emerged as promising therapeutic agents for a wide range of conditions. This review presents compelling findings, demonstrating the remarkable achievements of biologically synthesized CuO NPs as therapeutic agents. Their unique properties and mechanisms enable effective combating against cancer cells and various harmful microbial infections. CuO NPs exhibit potent anticancer activity through diverse mechanisms, including induction of apoptosis, inhibition of angiogenesis, and modulation of signaling pathways. Additionally, their antimicrobial activity manifests through various mechanisms, such as disrupting microbial membranes, generating reactive oxygen species, and interfering with microbial enzymes. This review offers valuable insights into the substantial potential of biologically synthesized CuO NPs as an alternative approach for future therapeutic interventions against cancer and microbial infections.

Keywords: biological synthesis, copper oxide nanoparticles, microbial infection, nanotechnology

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Authors: Eun-Young Kwon, Myung-Sook Choi, Su-Jung Cho, Ji-Young Choi, So Young Kim, Youngji Han

Abstract:

Overweight and obesity have been linked to a low-grade chronic inflammatory response and an increased risk of developing metabolic syndrome including insulin resistance, type 2 diabetes mellitus and certain types of cancers. Luteolin is a dietary flavonoid with anti-inflammatory, anti-oxidant, anti-cancer and anti-diabetic properties. However, little is known about the detailed mechanism associated with the effect of luteolin on inflammation-related obesity and its complications. The aim of the present study was to reveal the anti-diabetic effect of luteolin in diet-induced obesity mice using “transcriptomics” tool. Thirty-nine male C57BL/6J mice (4-week-old) were randomly divided into 3 groups and were fed normal diet, high-fat diet (HFD, 20% fat) and HFD+0.005% (w/w) luteolin for 16 weeks. Luteolin improved insulin resistance, as measured by HOMA-IR and glucose tolerance, along with preservation action of pancreatic β-cells, compared to the HFD group. Luteoiln was significantly decreased the levels of leptin and ghrelin that play a pivotal role in energy balance, and the macrophage low-grade inflammation marker sCD163 (soluble Cd antigen 163) in plasma. Activities of hepatic anti-oxidant enzymes (catalase and glutathione peroxidase) were increased, while the levels of plasma transaminase (GOT and GPT) and oxidative damage markers (hepatic mitochondria H2O2 and TBARS) were markedly decreased by luteolin supplementation. In addition, luteolin increased oxidative capacity and fatty acid utilization by presenting decrease in enzyme activities of citrate synthase, cytochrome C oxidase and β-hydroxyacyl CoA dehydrogenase and UCP3 gene expression compared to high-fat diet. Moreover, our microarray results of muscle also revealed down-regulated gene expressions associated with TCA cycle by HFD were reversed to normal level by luteolin treatment. Taken together, our results indicate that luteolin is one of bioactive components for improving insulin resistance by increasing oxidative capacity, modulating anti-oxidant metabolism and suppressing inflammatory signaling cascades in diet-induced obese mice. These results provide possible therapeutic targets for prevention and treatment of diet-induced obesity and its complications.

Keywords: anti-oxidant metabolism, diabetes, luteolin, oxidative capacity

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Authors: Niharul Alam

Abstract:

The development of energy efficient, economic and eco-friendly synthetic protocols for metal nanoparticles (NPs) with tailor-made structural properties and biocompatibility is a highly cherished goal for researchers working in the field of nanoscience and nanotechnology. In this context, green chemistry is highly relevant and the 12 principles of Green Chemistry can be explored to develop such synthetic protocols which are practically implementable. One of the most promising green chemical synthetic methods which can serve the purpose is biogenic synthetic protocol, which utilizes non-toxic multifunctional reactants derived from natural, biological sources ranging from unicellular organisms to higher plants that are often characterized as “medicinal plants”. Over the past few years, a plethora of medicinal plants have been explored as the source of this kind of multifunctional green chemical agents. In this presentation, we focus on the syntheses of stable monometallic Au and Ag NPs and also bimetallic Au/Ag alloy NPs with highly efficient catalytic property using aqueous extract of leaves of Indian Curry leaf plat (Murraya koenigii Spreng.; Fam. Rutaceae) as green multifunctional agents which is extensively used in Indian traditional medicine and cuisine. We have also studied the interaction between the synthesized metal NPs and surface-adsorbed fluorescent moieties, quercetin and quercetin glycoside which are its chemical constituents. This helped us to understand the surface property of the metal NPs synthesized by this plant based biogenic route and to predict a plausible mechanistic pathway which may help in fine-tuning green chemical methods for the controlled synthesis of various metal NPs in future. We observed that simple experimental parameters e.g. pH and temperature of the reaction medium, concentration of multifunctional agent and precursor metal ions play important role in the biogenic synthesis of Au NPs with finely tuned structures.

Keywords: green multifunctional agent, metal nanoparticles, biogenic synthesis

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Authors: Jihoon Yang, Jeong II Choi

Abstract:

Mincle is expressed in macrophages and is members of immunoreceptors induced after exposure to various stimuli and stresses. Mincle receptor activation promotes the production of these substances by increasing the transcription of inflammatory cytokines and chemokines. Cytokines, which play an important role in the initiation and maintenance of such inflammatory pain diseases, have a significant effect on sensory neurons in addition to their enhancement and inhibitory effects on immune and inflammatory cells as mediators of cell interaction. Glial cells in the central nervous system play a critical role in development and maintenance of chronic pain states. Microglia are tissue-resident macrophages in the central nervous system, and belong to a group of mononuclear phagocytes. In the central nervous system, mincle receptor is present in neurons and glial cells of the brain.This study was performed to identify the Mincle receptor in the spinal cord and to investigate the effect of Mincle receptor activation on nociception and the changes of microglia. Materials and Methods: C-type lectins(Mincle) was identified in spinal cord of Male Sprague–Dawley rats. Then, mincle receptor ligand (TDB), via an intrathecal catheter. Mechanical allodynia was measured using von Frey test to evaluate the effect of intrathecal injection of TDB. Result: The present investigation shows that the intrathecal administration of TDB in the rat produces a reliable and quantifiable mechanical hyperalgesia. In addition, The mechanical hyperalgesia after TDB injection gradually developed over time and remained until 10 days. Mincle receptor is identified in the spinal cord, mainly expressed in neuronal cells, but not in microglia or astrocyte. These results suggest that activation of mincle receptor pathway in neurons plays an important role in inducing activation of microglia and inducing mechanical allodynia.

Keywords: mincle, spinal cord, pain, microglia

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Authors: Lanlan Xiao, Yang Liu, Shuo Chen, Bingmei Fu

Abstract:

Most cancer-related deaths are due to metastasis. Metastasis is a complex, multistep processes including the detachment of cancer cells from the primary tumor and the migration to distant targeted organs through blood and/or lymphatic circulations. During hematogenous metastasis, the emigration of tumor cells from the blood stream through the vascular wall into the tissue involves arrest in the microvasculature, adhesion to the endothelial cells forming the microvessel wall and transmigration to the tissue through the endothelial barrier termed as extravasation. The narrow slit between endothelial cells that line the microvessel wall is the principal pathway for tumor cell extravasation to the surrounding tissue. To understand this crucial step for tumor hematogenous metastasis, we used Dissipative Particle Dynamics method to investigate an individual cell passing through a narrow slit numerically. The cell membrane was simulated by a spring-based network model which can separate the internal cytoplasm and surrounding fluid. The effects of the cell elasticity, cell shape and cell surface area increase, and slit size on the cell transmigration through the slit were investigated. Under a fixed driven force, the cell with higher elasticity can be elongated more and pass faster through the slit. When the slit width decreases to 2/3 of the cell diameter, the spherical cell becomes jammed despite reducing its elasticity modulus by 10 times. However, transforming the cell from a spherical to ellipsoidal shape and increasing the cell surface area only by 3% can enable the cell to pass the narrow slit. Therefore the cell shape and surface area increase play a more important role than the cell elasticity in cell passing through the narrow slit. In addition, the simulation results indicate that the cell migration velocity decreases during entry but increases during exit of the slit, which is qualitatively in agreement with the experimental observation.

Keywords: dissipative particle dynamics, deformability, surface area increase, cell migration

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Authors: Abir O. El Sadik

Abstract:

Introduction: Wound healing involves the interaction of multiple biological processes among different types of cells, intercellular matrix and specific signaling factors producing enhancement of cell proliferation of the epidermis over dermal granulation tissue. Several studies investigated multiple strategies to promote wound healing and to minimize infection and fluid losses. However, burn crisis, and its related morbidity and mortality are still elevated. The aim of the present study was to examine the effects of mesenchymal stem cells (MSCs) in accelerating wound healing and to compare the most efficient route of administration of MSCs, either intradermal or systemic injection, with focusing on the mechanisms producing epidermal and dermal cell regeneration. Material and methods: Forty-two adult male Sprague Dawley albino rats were divided into three equal groups (fourteen rats in each group): control group (group I); full thickness surgical skin wound model, Group II: Wound treated with systemic injection of MSCs and Group III: Wound treated with intradermal injection of MSCs. The healing ulcer was examined on day 2, 6, 10 and 15 for gross morphological evaluation and on day 10 and 15 for fluorescent, histological and immunohistochemical studies. Results: The wounds of the control group did not reach complete closure up to the end of the experiment. In MSCs treated groups, better and faster healing of wounds were detected more than the control group. Moreover, the intradermal route of administration of stem cells increased the rate of healing of the wounds more than the systemic injection. In addition, the wounds were found completely healed by the end of the fifteenth day of the experiment in all rats of the group injected intradermally. Microscopically, the wound areas of group III were hardly distinguished from the adjacent normal skin with complete regeneration of all skin layers; epidermis, dermis, hypodermis and underlying muscle layer. Fully regenerated hair follicles and sebaceous glands in the dermis of the healed areas surrounded by different arrangement of collagen fibers with a significant increase in their area percent were recorded in this group more than in other groups. Conclusion: MSCs accelerate the healing process of wound closure. The route of administration of MSCs has a great influence on wound healing as intradermal injection of MSCs was more effective in enhancement of wound healing than systemic injection.

Keywords: intradermal, mesenchymal stem cells, morphology, skin wound, systemic injection

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Authors: Ramatu I. Sha’aba, Mathias A. Chia, Abdullahi B. Alhassan, Yisa A. Gana, Ibrahim M. Gadzama

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Globally, Diclofenac (DLC) and Ibuprofen (IBU) are the most prescribed drugs due to their antipyretic and analgesic properties. They are, however, highly toxic at elevated doses, with the involvement of an already described oxidative stress pathway. As a result, there is rising concern about the ecological fate of analgesics on non-target organisms such as Daphnia magna and Phytoplankton species. Phytoplankton is a crucial component of the aquatic ecosystem that serves as the primary producer at the base of the food chain. However, the increasing presence and levels of micropollutants such as these analgesics can disrupt their community structure, dynamics, and ecosystem functions. This study presents a comprehensive series of the physiology, antioxidant response, immobilization, and risk assessment of Diclofenac and Ibuprofen’s effects on Daphnia magna and the Phytoplankton community using a laboratory approach. The effect of DLC and IBU at 27.16 µg/L and 20.89 µg/L, respectively, for a single exposure and 22.39 µg/L for combined exposure of DLC and IBU for the experimental setup. The antioxidant response increased with increasing levels of stress. The highest stressor to the organism was 1000 µg/L of DLC and 10,000 µg/L of IBU. Peroxidase and glutathione -S-transferase activity was higher for Diclofenac + Ibuprofen. The study showed 60% and 70% immobilization of the organism at 1000 g L-1 of DLC and IBU. The two drugs and their combinations adversely impacted Phytoplankton biomass with increased exposure time. However, combining the drugs resulted in more significant adverse effects on physiological and pigment content parameters. The risk assessment calculation for the risk quotient and toxic unit of the analgesic reveals from this study was RQ Diclofenac = 8.41, TU Diclofenac = 3.68, and RQ Ibuprofen = 718.05 and TU Ibuprofen = 487.70. Hence, these findings demonstrate that the current exposure concentrations of Diclofenac and Ibuprofen can immobilize D. magna. This study shows the dangers of multiple drugs in the aquatic environment because their combinations could have additive effects on the structure and functions of Phytoplankton and are capable of immobilizing D. magna.

Keywords: algae, analgesic drug, daphnia magna, toxicity

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Authors: Pascal U. Onu, Doris A. Ogbang, Emmanuel Okechukwu.

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Background: Plastics in their various forms have become ubiquitous in a very short space of time. This ubiquitous nature has plagued and daunted nations globally, overwhelming their ability to manage the environmental impact, especially its linkages to climate change. This has mobilized nations globally and triggered debates on the best approaches to ensure sustainability in terms of its production and utilization, as total elimination seems unrealistic. Objective: This study undertook to understand the pattern of plastic waste management, and its pollution awareness levels by the residents of the study area. Methods: Data were obtained through questionnaires designed specifically for plastic waste and qualitatively via journals and articles. Simple descriptive survey techniques with a survey population size of 300 respondents using kobo collect were employed. Results: Analysis based on disaggregated data indicated a proportionate distribution among male and female respondents (53% male and 47% female, respectively). Overall awareness levels on plastic waste's contribution to climate change, compared to its environmental impact, are reflective of a dire need for increased efforts in strengthening awareness creation, especially across gender populations and religious backgrounds. Drainage blockage topped the ranks among common problems caused by plastic waste within the area. Various plastic waste disposal methods were ranked, while pro-environmental measures for reducing the waste menace showed more willingness from males at 52%. Conclusion: These outcomes are instructive and suggest the need for renewed and increased awareness/education on the nexus of plastic pollution to climate change and also appropriate synergies/collaboration between government, private sector, and local communities, especially in the area of recycling to improve sustainability in plastic waste management.

Keywords: plastic waste, KAP, climate change, Nigeria

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Authors: Brian Chi Yan Cheng, Hui Guo, Tao Su, Xiu‐qiong Fu, Ting Li, Zhi‐ling Yu

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Rheumatoid arthritis (RA) affects around 1% of the globe population. Yet, there is still no cure for RA. Toll-like receptor 4 (TLR4) signalling has been found to be involved in the pathogenesis of RA, making it a potential therapeutic target for RA treatment. A herbal formula (RL) consisting of fruits of Rosa Multiflora (Eijitsu rose) and flowers of Lonicera Japonica (Japanese honeysuckle) has been used in treating various inflammatory disorders for more than a thousand year. Both of them are rich sources of nutrients and bioactive phytochemicals, which can be used in producing different food products and supplements. In this study, we would evaluate the anti-arthritic effect of RL on collagen-induced arthritis (CIA) in rats and investigate the involvement of TLR4 signaling in the mode of action of RL. Anti-arthritic efficacy was evaluated using CIA rats induced by bovine type II collagen. The treatment groups were treated with RL (82.5, 165, and 330 mg/kg bw per day, p.o.) or positive control indomethacin (0.25 mg/kg bw per day, p.o.) for 35 days. Clinical signs (hind paw volume and arthritis severity scores), changes in serum inflammatory mediators, pro-/antioxidant status, histological and radiographic changes of joints were investigated. Spleens and peritoneal macrophages were used to determine the effects of RL on innate and adaptive immune responses in CIA rats. The involvement of TLR4 signalling pathways in the anti-arthritic effect of RL was examined in cartilage tissue of CIA rats, murine RAW264.7 macrophages and human THP-1 monocytic cells. The severity of arthritis in the CIA rats was significantly attenuated by RL. Antioxidant status, histological score and radiographic score were efficiently improved by RL. RL could also dose-dependently inhibit pro-inflammatory cytokines in serum of CIA rats. RL significantly inhibited the production of various pro-inflammatory mediators, the expression and/or activity of the components of TLR4 signalling pathways in animal tissue and cell lines. RL possesses anti-arthritic effect on collagen-induced arthritis in rats. The therapeutic effect of RL may be related to its inhibition on pro-inflammatory cytokines in serum. The inhibition of the TAK1/NF-κB and TAK1/MAPK pathways participate in the anti-arthritic effects of RL. This provides a pharmacological justification for the dietary use of RL in the control of various arthritic diseases. Further investigation should be done to develop RL into a anti-arthritic food products and/or supplements.

Keywords: japanese honeysuckle, rheumatoid arthritis, rosa multiflora, rosehip

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Authors: Henry Memczak, Marc Hovestaedt, Bernhard Ay, Sandra Saenger, Thorsten Wolff, Frank F. Bier

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The influenza viruses cause flu epidemics every year and serious pandemics in larger time intervals. The only cost-effective protection against influenza is vaccination. Due to rapid mutation continuously new subtypes appear, what requires annual reimmunization. For a correct vaccination recommendation, the circulating influenza strains had to be detected promptly and exactly and characterized due to their antigenic properties. During the flu season 2016/17, a wrong vaccination recommendation has been given because of the great time interval between identification of the relevant influenza vaccine strains and outbreak of the flu epidemic during the following winter. Due to such recurring incidents of vaccine mismatches, there is a great need to speed up the process chain from identifying the right vaccine strains to their administration. The monitoring of subtypes as part of this process chain is carried out by national reference laboratories within the WHO Global Influenza Surveillance and Response System (GISRS). To this end, thousands of viruses from patient samples (e.g., throat smears) are isolated and analyzed each year. Currently, this analysis involves complex and time-intensive (several weeks) animal experiments to produce specific hyperimmune sera in ferrets, which are necessary for the determination of the antigen profiles of circulating virus strains. These tests also bear difficulties in standardization and reproducibility, which restricts the significance of the results. To replace this test a peptide-based assay for influenza virus subtyping from corresponding virus samples was developed. The differentiation of the viruses takes place by a set of specifically designed peptidic recognition molecules which interact differently with the different influenza virus subtypes. The differentiation of influenza subtypes is performed by pattern recognition guided by machine learning algorithms, without any animal experiments. Synthetic peptides are immobilized in multiplex format on various platforms (e.g., 96-well microtiter plate, microarray). Afterwards, the viruses are incubated and analyzed comparing different signaling mechanisms and a variety of assay conditions. Differentiation of a range of influenza subtypes, including H1N1, H3N2, H5N1, as well as fine differentiation of single strains within these subtypes is possible using the peptide-based subtyping platform. Thereby, the platform could be capable of replacing the current antigenic characterization of influenza strains using ferret hyperimmune sera.

Keywords: antigenic characterization, influenza-binding peptides, influenza subtyping, influenza surveillance

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