Search results for: inflammatory mediators

Authors: Beata Skibska, Andrzej Stanczak, Agnieszka Skibska

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Nanodiamond (ND) is a carbon nanomaterial that has high biocompatibility, and it has a very positive effect on a number of biochemical processes. NDs have great potential in treating multiple inflammation-associated diseases. The purpose of this study was to investigate the anti-inflammatory effect of nanodiamonds and lipoic acid (LA) (as antioxidants) on rats' cardiovascular systems after lipopolysaccharide (LPS) administration. Animal experiments enabled the determination of how nanodiamonds act when applied independently or in combination with lipoic acid. The effect of NDs and LA on C-reactive protein (CRP) levels and heart edema was evaluated. NDs and LA administered after LPS administration attenuated heart edema and significantly decreased the CRP level. The results suggest that NDs and LA play an important role in LPS-induced inflammation in the heart. NDs find new applications in modern biomedical science and biotechnologies.

Keywords: nanodiamonds, lipoic acid, inflammation, cardiovascular system

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Authors: Maria Luisa Barcena De Arellano, Sofya Pozdniakova, Pavelas Karkacas, Anja Kuhl, Istvan Baczko, Yury Ladilov, Vera Regitz-Zagrosek

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Introduction: Aging is associated with deterioration of the physiological function, leading to systemic inflammation and mitochondrial dysfunction that promote the development of cardiovascular diseases. Sex differences in aging-related cardiovascular diseases have been postulated. However, their precise mechanisms remain unclear. In the current study, we aimed to investigate the sex difference in the age-related alteration in Sirt1-AMPK signaling and its relation to the mitochondrial biogenesis and inflammation. Methods: Male and female human non-disease lateral left ventricular wall tissue (young (17–40 years; n= 7 male and 7 female) and old (50–68 years; n= 9 male and 8 female)) were used. qRT-PCR, western blot and immunohistochemistry assays were performed for expression analyses of Sirt1, AMPK, pAMPK, ac-Ku70, TFAM, PGC-1α, Sirt3, SOD2 and catalase. CD68 was used as a marker for macrophages and the ratio of IL-12:IL10 (pro-inflammatory phenotype (high IL-12/low IL-10) and anti-inflammatory phenotype (low IL-12/high IL-10) was used to examine the inflammatory stage in the heart. Results: Sirt1 expression was significantly higher in young females compared to young males, whereas in aged hearts Sirt1 expression was significantly downregulated in females, but not in males. In line with the Sirt1 downregulation in aged females, acetylation of nuclear Ku70, a direct target of Sirt1, in aged female hearts was significantly elevated. The activity of AMPK was significantly decreased in aged individuals, however no sex differences in the AMPK expression or activity were found in young or old individuals. The expression of mitochondrial proteins TOM40, SOD2 and Sirt3 was significantly higher in young females compared to young males, while in aged female hearts SOD2 and TOM40 were downregulated. In addition, the expression of catalase, a key cytosolic and mitochondrial anti-oxidative enzyme was significantly higher in young females and this female sex benefit was lost in aged hearts. In addition, the number of cardiac macrophages was significantly increased in old female, but not in male hearts. Consistently, the pro-inflammatory shift in old females was further confirmed by differences in the IL12/IL10 ratio in young female cardiac tissue in a favour of the anti-inflammatory mediator IL-10 (ratio 1:4) compared to young males (ratio 1:1). The anti-inflammatory environment in the heart was lost in aged females (ratio 1:1). Conclusion: Aging leads to the significant downregulation of Sirt1 expression and elevated acetylation of Ku70 in female, but not in male hearts. Furthermore, a beneficial upregulation of mitochondrial and anti-oxidative proteins in young females is lost with aging. Moreover, the malfunctions in the expression of Sirt1 and mitochondrial proteins in aged female hearts is accompanied by a significant pro-inflammatory shift. The study provides a molecular basis for the increased incidence of cardiovascular diseases in old women.

Keywords: inflammation, mitochondrial dysfunction, aging, Sirt1-AMPK axis

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Authors: Murtada Ahmed Oshi, Jin-Wook Yoo

Abstract:

Layer-by-layer (LBL) coating has gained popularity for drug delivery of therapeutic drugs. Herein we described a novel approach for enhancing the therapeutic efficiency of the locally administered dexamethasone (Dex) for inflammatory bowel disease (IBD). We utilized a LBL-coating technique on Dex microcrystals (DexMCs) with multiple layers of polyelectrolytes composed of poly (allylamine hydrochloride) (PAH), poly (sodium 4-styrene sulfonate) (PSS) and Eudragit® S100 (ES). The successful deposition of the layers onto DexMCs surfaces were confirmed through zeta potential measurement and confocal laser scanning microscopy. The surface morphology was investigated through scanning electron microscopy. The drug encapsulation efficiency was 95% with a mean particle size of 2 µm and negative surface charge (-40 mV). Moreover, in vitro drug release study showed a minimum release of the drug ( 15%) at an acidic condition during initial first 5 h, followed by sustained-release at an alkaline condition. For in vivo study, LBL-DxMCs were administered orally to ICR mice suffering from dextran sulfate sodium-induced colitis. LBL-DxMCs substantially enhanced anti-IBD activities as compared to DxMCs. Macroscopic, histological and biochemical (tumor necrosis factor-α, interleukin-6 and myeloperoxidase) examinations revealed marked improvements of colitis signs in the mice treated with LBL-DxMCs compared with those treated with DxMCs. Overall, LBL-DxMCs could be a suitable candidate for the treatment of IBD.

Keywords: dexamethasone, inflammatory bowel disease, LBL-coating, polyelectrolytes

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Authors: Qing Zhang, Janak L. Pathak, Macro N. Helder, Richard T. Jaspers, Yin Xiao

Abstract:

Introduction: Nanomaterial-based bone regeneration is greatly influenced by the immune microenvironment. Tissue-engineered nanomaterials mediate the inflammatory response of macrophages to regulate bone regeneration. Silica nanoparticles have been widely used in tissue engineering-related preclinical studies. However, the effect of topological features on the surface of silica nanoparticles on the immune response of macrophages remains unknown. Purposes: The aims of this research are to compare the influences of normal and pollen-like silica nano-surface topography on macrophage immune responses and to obtain insight into their potential regulatory mechanisms. Method: Macrophages (RAW 264.7 cells) were exposed to mesoporous silica nanoparticles with normal morphology (MSNs) and pollen-like morphology (PMSNs). RNA-seq, RT-qPCR, and LSCM were used to assess the changes in expression levels of immune response-related genes and proteins. SEM and TEM were executed to evaluate the contact and adherence of silica nanoparticles by macrophages. For the assessment of the immunomodulation-mediated osteogenic potential, BMSCs were cultured with conditioned medium (CM) from LPS pre-stimulated macrophage cultures treated with MSNs or PMSNs. Osteoimmunomodulatory potential of MSNs and PMSNs in vivo was tested in a mouse cranial bone osteolysis model. Results: The results of the RNA-seq, RT-qPCR, and LSCM assays showed that PMSNs inhibited the expression of pro-inflammatory genes and proteins in macrophages. SEM images showed distinct macrophage membrane surface binding patterns of MSNs and PMSNs. MSNs were more evenly dispersed across the macrophage cell membrane, while PMSNs were aggregated. PMSNs-induced macrophage anti-inflammatory response was associated with upregulation of the cell surface receptor CD28 and inhibition of ERK phosphorylation. TEM images showed that both MSNs and PMSNs could be phagocytosed by macrophages, and inhibiting nanoparticle phagocytosis did not affect the expression of anti-inflammatory genes and proteins. Moreover, PMSNs-induced conditioned medium from macrophages enhanced BMP-2 expression and osteogenic differentiation mBMSCs. Similarly, PMSNs prevented LPS-induced bone resorption via downregulation of inflammatory reaction. Conclusions: PMSNs can promote bone regeneration by modulating osteoimmunological processes through surface topography. The study offers insights into how surface physical contact cues can modulate the regulation of osteoimmunology and provides a basis for the application of nanoparticles with pollen-like morphology to affect immunomodulation in bone tissue engineering and regeneration.

Keywords: physical contact, osteoimmunology, macrophages, silica nanoparticles, surface morphology, membrane receptor, osteogenesis, inflammation

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Authors: Wan-Ting Shen, Ching-Liang Hsieh, Yi-Wen Lin

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Electroacupuncture (EA) has been reported effective for many kinds of pain and is a common treatment for acute or chronic pain. However, to date, there are limited studies examining the effect of acupuncture dosage. In our experiment, after injecting mice with Complete Freund’s Adjuvant (CFA) to induce inflammatory pain, two groups of mice were administered two different 15 min EA treatments at 2Hz. The first group received EA at a single acupuncture point (ST36, Zusanli) in both legs (two points), whereas the second group received two acupuncture points in both legs (four points) and the analgesic effect was compared. It was found that double points (ST36, Zusanli and SP6, Sanyinjiao) were significantly superior to single points (ST36, Zusanli) when evaluated using the electronic von Frey Test (mechanic) and Hargreaves’ Test (thermal). Through this study, it is expected more novel physiological mechanisms of acupuncture analgesia will be discovered.

Keywords: anti-inflammation, dose effect, electroacupuncture, pain control

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Authors: Abdelkader H. El Debani, Huda Gargoum, Awad G. Abdellatif

Abstract:

The aim of this study is to investigate analgesic and the anti-inflammatory effects Camel Thorn Extract (CTE) in rodents. Male albino mice weighing 20-25 gm. were divided into different groups each of 8 mice. The control was given normal saline i. p., the first group was given normal saline i. p. the 2nd, 3rd, 4th, groups received different doses of CTE (330, 660, and 1300 mg/kg) respectively and the 6th group received 5mg/kg of morphine i. p. All groups (except the control group) were given acetic acid 40 min after receiving the different treatment. The number of writhes was recorded 5 min after acetic acid injection for 15 min and the % of inhibition of writhing were calculated. Different groups of rats weighing 180- 220 gm., were divided into three groups each of 5 rats. At the beginning, the volumes of the right and left paw in animals were measured by using of the plethysmometer. The 1st group was given 660 mg /kg i. p. of CTE, the 2nd group received indomethacin (5 mg/kg i. p.). One hour later, edema was induced by sub planter injection of 0.1 ml of 1 % freshly prepared suspension of carrageenan into the right hind paws of the rats. The volume of the injected paws and contra-lateral paws were measured at 0, 0.5, 1, 2, 3, 4, and 5 hours using plethysmometer. The volume of the left paw of the rat was subtracted from the volume of the right paw of the same animal. Our results showed that 330,660 and 1300 mg/kg produced 14, 49 and 84%of inhibition of writhes, indicating that CTE has a strong analgesic activity. Our data also showed that the % of inhibition of edema at 30, 60, 120, 180, and 240 min was 14,51,71,61, and 56% in the animals given camel thorn extract whereas these figures in animals given endomethacin were 14, 24, 54, 52, and 54%. These results indicate that camel thorn has anti-inflammatory activities. The mechanism of analgesic and anti-inflammatory activities needs further investigations.

Keywords: camel thorn, imdomethacin, morphine, pharmaceutical medicine

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Authors: Carolina N. França, Jônatas B. do Amaral, Maria C.O. Izar, Ighor L. Teixeira, Francisco A. Fonseca

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Introduction: Atherosclerosis is a progressive disease, characterized by lipid and fibrotic element deposition in large-caliber arteries. Conditions related to the development of atherosclerosis, as dyslipidemia, hypertension, diabetes, and smoking are associated with endothelial dysfunction. There is a frequent recurrence of cardiovascular outcomes after acute myocardial infarction and, at this sense, cycles of mobilization of monocyte subtypes (classical, intermediate and nonclassical) secondary to myocardial infarction may determine the colonization of atherosclerotic plaques in different stages of the development, contributing to early recurrence of ischemic events. The recruitment of different monocyte subsets during inflammatory process requires the expression of chemokine receptors CCR2, CCR5, and CX3CR1, to promote the migration of monocytes to the inflammatory site. The aim of this study was to evaluate the effect of lipid-lowering treatment by six months in the monocyte phenotype and chemokine receptor levels of patients after Acute Myocardial Infarction (AMI). Methods: This is a PROBE (prospective, randomized, open-label trial with blinded endpoints) study (ClinicalTrials.gov Identifier: NCT02428374). Adult patients (n=147) of both genders, ageing 18-75 years, were randomized in a 2x2 factorial design for treatment with rosuvastatin 20 mg/day or simvastatin 40 mg/day plus ezetimibe 10 mg/day as well as ticagrelor 90 mg 2x/day and clopidogrel 75 mg, in addition to conventional AMI therapy. Blood samples were collected at baseline, after one month and six months of treatment. Monocyte subtypes (classical - inflammatory, intermediate - phagocytic and nonclassical – anti-inflammatory) were identified, quantified and characterized by flow cytometry, as well as the expressions of the chemokine receptors (CCR2, CCR5 and CX3CR1) were also evaluated in the mononuclear cells. Results: After six months of treatment, there was an increase in the percentage of classical monocytes and reduction in the nonclassical monocytes (p=0.038 and p < 0.0001 Friedman Test), without differences for intermediate monocytes. Besides, classical monocytes had higher expressions of CCR5 and CX3CR1 after treatment, without differences related to CCR2 (p < 0.0001 for CCR5 and CX3CR1; p=0.175 for CCR2). Intermediate monocytes had higher expressions of CCR5 and CX3CR1 and lower expression of CCR2 (p = 0.003; p < 0.0001 and p = 0.011, respectively). Nonclassical monocytes had lower expressions of CCR2 and CCR5, without differences for CX3CR1 (p < 0.0001; p = 0.009 and p = 0.138, respectively). There were no differences after the comparison between the four treatment arms. Conclusion: The data suggest a time-dependent modulation of classical and nonclassical monocytes and chemokine receptor levels. The higher percentage of classical monocytes (inflammatory cells) suggest a residual inflammatory risk, even under preconized treatments to AMI. Indeed, these changes do not seem to be affected by choice of the lipid-lowering strategy.

Keywords: acute myocardial infarction, chemokine receptors, lipid-lowering treatment, monocyte subtypes

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Authors: Fakhrosadat Sajjadian

Abstract:

In the USA, about 5% of women diagnosed with breast cancer annually are affected by Inflammatory Breast Cancer (IBC), which is a highly aggressive type of Locally Advanced Breast Cancer (LABC). It is a type of LABC that is clinically and pathologically different, known for its rapid growth, invasiveness, and ability to promote the growth of blood vessels. Almost all women are found to have lymph nodes affected upon diagnosis, while around 36% show obvious distant metastases. Even with the latest improvements in multimodality therapies, the outlook for patients with IBC remains bleak, as the average disease-free survival time is less than 2.5 years. Recent research on the genetic factors responsible for the IBC phenotype has resulted in the discovery of genes that play a role in the advancement of this illness. The development of primary human cell lines and animal models has assisted in this research. These advancements offer new possibilities for future actions in identifying and treating IBC.

Keywords: breast cancer, inflammation, diagnosis, IBC, LABC

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Authors: B. M. Pardeshi

Abstract:

Introduction: Minerals and trace elements are chemical elements required by our bodies for numerous biological and physiological processes that are necessary for the maintenance of health. Medicinal plants are highly beneficial for the maintenance of good health and prevention of diseases. They are known as potential sources of minerals and vitamins. 30 to 40% of today’s conventional drugs used in the medicinal and curative properties of various plants are employed in herbal supplement botanicals, nutraceuticals and drug. Aim: The authors explored the mineral element content of some herbs, because mineral elements may have significant role in the development and treatment of gastrointestinal diseases, and a close connection between the presence or absence of mineral elements and inflammatory mediators was noted. Methods: Present study deals with the elemental analysis of medicinal plants by Instrumental Neutron activation Analysis and Atomic Absorption Spectroscopy. Medicinal herbals prescribed for skin diseases were purchased from markets and were analyzed by Instrumental Neutron Activation Analysis (INAA) using 252Cf Californium spontaneous fission neutron source (flux* 109 n s-1) and the induced activities were counted by γ-ray spectrometry and Atomic Absorption Spectroscopy (AAS) techniques (Perkin Elmer 3100 Model) available at Department of Chemistry University of Pune, India, was used for the measurement of major, minor and trace elements. Results: 15 elements viz. Al, K, Cl, Na, Mn by INAA and Cu, Co, Pb Ni, Cr, Ca, Fe, Zn, Hg and Cd by AAS were analyzed from different medicinal plants from India. A critical examination of the data shows that the elements Ca , K, Cl, Al, and Fe are found to be present at major levels in most of the samples while the other elements Na, Mn, Cu, Co, Pb, Ni, Cr, Ca, Zn, Hg and Cd are present in minor or trace levels. Conclusion: The beneficial therapeutic effect of the studied herbs may be related to their mineral element content. The elemental concentration in different medicinal plants is discussed.

Keywords: instrumental neutron activation analysis, atomic absorption spectroscopy, medicinal plants, trace elemental analysis, mineral contents

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Authors: Benoit Jauniaux, Azzam Ismail

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Objectives: The aims were to identify all incident adult cases of idiopathic inflammatory myopathies (IIMs) in the City of Leeds, UK, and to estimate the risk of cancer in IIMs as compared with the general population. Methods: Cases of IIMs were ascertained by review of all muscle biopsy reports from the Neuropathology Laboratory. A review of medical records was undertaken for each case to review the clinical diagnosis and collect epidemiological data such as age, ethnicity, sex, and comorbidities, including cancer. Leeds denominator population numbers were publicly obtainable. Results: Two hundred and six biopsy reports were identified, and after review, 50 incident cases were included in the study between June 2010 and January 2021. Out of the 50 cases, 27 were male, and 23 were female. The mean incidence rate of IIMs in Leeds throughout the study period was 7.42/1 000 000 person years. The proportion of IIMs cases with a confirmed malignancy was 22%. Compared to the general population, the relative risk of cancer was significantly greater in the IIMs population(31.56, P < 0.01). Conclusions: The incidence rate of IIMs in Leeds was consistent with data from previous literature, however, disagreement exists between different methods of IIMs case inclusion due to varying clinical criteria and definitions. IIMs are associated with increased risk of cancer however, the pathogenesis of this relationship still requires investigating. This study supports the practice of malignancy screening and long-term surveillance in patients with IIMs.

Keywords: idiopathic inflammatory myopathies, myositis, polymyositis, dermatomyositis, malignancy, epidemiology, incidence rate, relative risk

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Authors: Azza A. Ali, Doaa M. Abd El-Latif, Amany M. Gad, Yasser M. A. Elnahas, Karema Abu-Elfotuh

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Background: Exposure to Aluminium (Al) has been increased recently. It is found in food products, food additives, drinking water, cosmetics and medicines. Chronic consumption of Al causes oxidative stress and has been implicated in several chronic disorders. Liver is considered as the major site for detoxification while kidney is involved in the elimination of toxic substances and is a target organ of metal toxicity. Social isolation (SI) or protein malnutrition (PM) also causes oxidative stress and has negative impact on Al-induced nephrotoxicity as well as hepatotoxicity. Coenzyme Q10 (CoQ10) is a powerful intracellular antioxidant with mitochondrial membrane stabilizing ability while wheat grass is a natural product with antioxidant, anti-inflammatory and different protective activities, cocoa is also potent antioxidants and can protect against many diseases. They provide different degrees of protection from the impact of oxidative stress. Objective: To study the impact of social isolation together with Protein malnutrition on nephro- and hepato-toxicity induced by chronic Al exposure in rats as well as to investigate the postulated protection using a combination of Co Q10, wheat grass and cocoa. Methods: Eight groups of rats were used; four served as protected groups and four as un-protected. Each of them received daily for five weeks AlCl3 (70 mg/kg, IP) for Al-toxicity model groups except one group served as control. Al-toxicity model groups were divided to Al-toxicity alone, SI- associated PM (10% casein diet) and Al- associated SI&PM groups. Protection was induced by oral co-administration of CoQ10 (200mg/kg), wheat grass (100mg/kg) and cocoa powder (24mg/kg) combination together with Al. Biochemical changes in total bilirubin, lipids, cholesterol, triglycerides, glucose, proteins, creatinine and urea as well as alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), lactate deshydrogenase (LDH) were measured in serum of all groups. Specimens of kidney and liver were used for assessment of oxidative parameters (MDA, SOD, TAC, NO), inflammatory mediators (TNF-α, IL-6β, nuclear factor kappa B (NF-κB), Caspase-3) and DNA fragmentation in addition to evaluation of histopathological changes. Results: SI together with PM severely enhanced nephro- and hepato-toxicity induced by chronic Al exposure. Co Q10, wheat grass and cocoa combination showed clear protection against hazards of Al exposure either alone or when associated with SI&PM. Their protection were indicated by the significant decrease in Al-induced elevations in total bilirubin, lipids, cholesterol, triglycerides, glucose, creatinine and urea levels as well as ALT, AST, ALP, LDH. Liver and kidney of the treated groups also showed significant decrease in MDA, NO, TNF-α, IL-6β, NF-κB, caspase-3 and DNA fragmentation, together with significant increase in total proteins, SOD and TAC. Biochemical results were confirmed by the histopathological examinations. Conclusion: SI together with PM represents a risk factor in enhancing nephro- and hepato-toxicity induced by Al in rats. CoQ10, wheat grass and cocoa combination provide clear protection against nephro- and hepatotoxicity as well as the consequent degenerations induced by chronic Al-exposure even when associated with the risk of SI together with PM.

Keywords: aluminum, nephrotoxicity, hepatotoxicity, isolation and protein malnutrition, coenzyme Q10, wheatgrass, cocoa, nutrients combinations

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Authors: Imene Soufli, Abdelkrim Hablal, Manel Amri, Moussa Labsi, Rania Sihem Boussa, Nassim Sid Idris, Chafia Touil-Boukoffa

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Crohn’s Disease (CD) is a relapsing–remitting inflammatory bowel disease with a progressive course. The aim of our study was to evaluate the relationship between the immunomarkers: Nitric Oxide (NO), pro-inflammatory cytokines, and blood count-based ratios and the outcome of corticosteroid or anti-TNF-α therapy in patients with complicated Crohn’s Disease. In this context, we evaluated the NLR as the ratio of neutrophil count to lymphocyte count, PLR as the ratio of platelet counts to lymphocyte count, and MLR as the ratio of monocyte count to lymphocyte count in patients and controls. Furthermore, we assessed NO production by the Griess method in plasma along with iNOS and NF-κB expression by immunofluorescence method in intestinal tissues of patients and controls. In the same way, we evaluated plasma TNF-α, IL-17A, and IL-10 levels using ELISA. Our results indicate that blood count-based ratios NLR, PLR, and MLR were significantly higher in patients compared to controls. In addition, increased systemic levels of NO, TNF-α, and IL-17A and colonic expression of iNOS and NF-κB were observed in the same patients. Interestingly, the high ratio of NLR and MLR, as well as NO production, was significantly decreased in treated patients. Collectively, our findings suggest that Nitric Oxide, as well as the blood count-based ratios (NLR, PLR, MLR), could constitute useful immuno-markers in complicated Crohn’s Disease, predicting the response to treatment

Keywords: complicated crohn’s disease, nitric oxide, blood count-based ratios, treatments, pro-inflammatory cytokines

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Authors: B. M. Pardeshi

Abstract:

Introduction: Minerals and trace elements are chemical elements required by our bodies for numerous biological and physiological processes that are necessary for the maintenance of health. Medicinal plants are highly beneficial for the maintenance of good health and prevention of diseases. They are known as potential sources of minerals and vitamins. 30 to 40% of today’s conventional drugs used in the medicinal and curative properties of various plants are employed in herbal supplement botanicals, nutraceuticals and drug. Aim: The authors explored the mineral element content of some herbs, because mineral elements may have significant role in the development and treatment of gastrointestinal diseases, and a close connection between the presence or absence of mineral elements and inflammatory mediators was noted. Methods: Present study deals with the elemental analysis of medicinal plants by Instrumental Neutron activation Analysis and Atomic Absorption Spectroscopy. Medicinal herbals prescribed for skin diseases were purchased from markets and were analyzed by Instrumental Neutron Activation Analysis (INAA) using 252Cf Californium spontaneous fission neutron source (flux * 109 n s-1) and the induced activities were counted by γ-ray spectrometry and Atomic Absorption Spectroscopy (AAS) techniques (Perkin Elmer 3100 Model) available at Department of Chemistry University of Pune, INDIA, was used for the measurement of major, minor and trace elements. Results: 15 elements viz. Al, K, Cl, Na, Mn by INAA and Cu, Co, Pb, Ni, Cr, Ca, Fe, Zn, Hg and Cd by AAS were analyzed from different medicinal plants from India. A critical examination of the data shows that the elements Ca , K, Cl, Al, and Fe are found to be present at major levels in most of the samples while the other elements Na, Mn, Cu, Co, Pb, Ni, Cr, Ca, Zn, Hg and Cd are present in minor or trace levels. Conclusion: The beneficial therapeutic effect of the studied herbs may be related to their mineral element content. The elemental concentration in different medicinal plants is discussed.

Keywords: instrumental neutron activation analysis, atomic absorption spectroscopy, medicinal plants, trace elemental analysis, mineral contents

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Authors: Aliya Tokbergenova, Maida Tusupbekova, Daulet Dzhangaliyev, Alena Lavrinenko

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Background: Odontogenic phlegmons are ranked the first among pyoinflammatory processes in the frequency of hospitalization in maxillofacial surgery in the post-Soviet countries. The main role in etiology is played by obligate anaerobes and aerobes. According to numerous data, the structure of aerobic pathogens is dominated by staphylococci and gram-negative bacteria. Aim: The research aim is to study the microflora of the purulent discharge odontogenic inflammatory processes. Materials and methods: A total of 220 patients have been examined, of which 120 patients aged 25-59 years have been included in the research who did not have comorbidity hospitalized in the maxillofacial hospital in Karaganda (Kazakhstan) from January 2016 to July 2017. The bacteriological research has been carried out on the basis of the multiaccess laboratory of the KSMU, through the Matrix Assisted Laser Desorption/Ionization (MALDI) apparatus. The material sample was pus from the inflammation focus, taken during the operating period. Results: According to the research among 120 patients (100%), 15 patients (12.5%) have had microorganisms not grown. From 105 (87.5%) bacteriological results, it has been revealed the following 1) Streptococcus: 51 (42.5%): Streptococcus beta-haemolytic: 17 (14.2%), Streptococcus pneumoniae: 12 (10%), Streptococcus anginosus: 8 (6.6%), Streptococcus oralis: 8 (6.6%), Streptococcus constellatus: 6 (5.0%); 2) Staphylococci: 27 (22.5%): Staphylococci aureus: 14 (11.7%) and Staphylococci epidermidis: 13 (10.8%); 3) Pseudomonas aeruginosa: 12 (10%); 4) Neisseria: 11 (9.1%): Neisseria mucosa: 5 (4.1%) and Neisseria macacae: 6 (5.0%); 5) Klebsiella pneumoniae: 2 (1.7%); 6) Stenotrophomonas maltophilia: 2 (1.7%). 15 patients (12.5%) experienced complications in the form of 1) The dissemination of the process in 10 patients (8.4%). 2) Osteomyelitis in 3 (2.5%). 3) Mediastinitis in 1 (0.8%). 4) Sinusitis in 1 (0.8%). 15 patients (100%) were carried out repeated bacteriological examination, the following was revealed: 1) Streptococcus: 10 (66.7%): Streptococcus beta-haemolytic: 4 (26.7%), Streptococcus pneumoniae: 2 (13.3%), Streptococcus аnginosus: 2 (13.3%), Streptococcus oralis: 1 (6.7%), Streptococcus constellatus: 1 (6.7%); 2) Staphylococci: 4 (26.7%): Staphylococci aureus: 3 (20%) and Staphylococci epidermidis: 1 (6.7%); 3) Pseudomonas aeruginosa: 1 (6.7%). Conclusions: Thus, according to our research data, streptococci predominate in the odontogenic processes microflora in aerobic flora in the central Kazakhstan region, which refutes the leading role of staphylococci in the development of odontogenic inflammatory processes, thus creating prerequisites for studying new treatment approaches.

Keywords: maxillofacial surgery, microflora, odontogenic phlegmons, pyo-inflammatory

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Authors: Sameh Al-Natour, Izak Benbasat

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The introduction of a multitude of new and interactive e-commerce information technology (IT) artifacts has impacted adoption research. Rather than solely functioning as productivity tools, new IT artifacts assume the roles of interaction mediators and social actors. This paper describes the varying roles assumed by IT artifacts, and proposes and distinguishes between four distinct foci of how the artifacts are evaluated. It further proposes a theoretical model that maps the different views of IT artifacts to four distinct types of evaluations.

Keywords: IT adoption, IT artifacts, similarity, social actor

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Authors: Abeer Y. Ibrahim, Faten M. Ibrahim, Samah A. El-Newary, Saber F. Hendawy

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Objective: Appreciation of in-vitro anti-inflammatory and antioxidant characters of Vitex agnus-castus berries alcoholic extract and fractions, as well as in-vivo antitumor ability of alcoholic extract and chloroform fraction against Ehrlich ascites carcinoma is the aim of this study. Material and methods: Antioxidant properties of crude alcoholic extract of vitex berries as well as petroleum ether, chloroform, ethyl acetate and butanol fractions were evaluated, in-vitro assessments, as compared with standard materials, l-ascorbic acid (vitamin C) and butylated hydroxyl toluene(BHT). The anti-inflammatory activity was investigated in cyclooxygenase (COX)-1 and COX-2 inhibition assays. Moreover, in-vivo antitumor effect of vitex berries alcoholic and chloroform extracts were evaluated using Ehrlich ascites carcinoma model. Data were presented as mean±SE, and data were analyzed by one-way analysis of variance test. Results and conclusion: Berries crude extract showed potent antioxidant activity followed with its fractions ethyl acetate and chloroform as compared with standard (V.C and BHT). Ethyl acetate fraction showed good reduction capability, metal ion chelation, hydrogen peroxide scavenging, nitric oxide scavenging and superoxide anion scavenging. Meanwhile, chloroform fraction produced the highest free radical scavenging activity and total antioxidant capacity. In respectable of lipid peroxidation inhibition, crude alcoholic extract and its fractions cleared weak inhibition in comparing with standard materials. Anti-inflammatory activity of V. agnus-castus berries chloroform fraction of vitex was best COX-2 inhibitor (IC₅₀, 135.41 µg/ ml) as compared to vitex alcoholic extract or ethyl acetate fraction with weak inhibitory effect on COX-1 (IC50, 778.432 µg/ ml), where the lowest effect on COX-1 was recorded with alcoholic extract. Alcoholic extract and its fractions showed weak COX-1 inhibition activity, whereas COX-2 was inhibited (100%), compared with celecoxib drug (72% at 1000ppm). The crude alcoholic and chloroform extracts of V. agnus-castus barries significantly reduced the viable Ehrlich cell count and increased nonviable count with amelioration of all hematological parameters. This amelioration was reflected on increasing median survival time and significant increase (P < 0.05) in lifespan.

Keywords: anti-inflammatory, antioxidants, ehrlich ascites carcinoma, Vitex agnus-castus

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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: Rachna Agarwal, R. Naveen, Darpan Thakre, Rohit Shahi, Maryam Abbasi, Upendra Rathore, Latika Gupta

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Aim: Retinal changes are the window to systemic vasculature. Therefore, we explored retinal changes in patients with idiopathic inflammatory myopathies (IIM) as a surrogate for vascular health. Methods: Adult and juvenile IIM patients visiting a tertiary care centre in 2021 satisfying the International Myositis Classification Criteria were enrolled for detailed ophthalmic examination in comparison with healthy controls (HC). Patients with conditions that precluded thorough posterior chamber examination were excluded. Scale variables are expressed as median (IQR). Multivariate analysis (binary logistic regression-BLR) was conducted, adjusting for age, gender, and comorbidities besides factors significant in univariate analysis. Results: 43 patients with IIM [31 females; age 36 (23-45) years; disease duration 5.5 (2-12) months] were enrolled for participation. DM (44%) was the most common diagnosis. IIM patients exhibited frequent attenuation of retinal vessels (32.6% vs. 4.3%, p <0.001), AV nicking (14% vs. 2.2%, p=0.053), and vascular tortuosity (18.6% vs. 2.2%, p=0.012), besides decreased visual acuity (53.5% vs. 10.9%, p<0.001) and immature cataracts (34.9% vs. 2.2%, p<0.001). Attenuation of vessels [OR 10.9 (1.7-71), p=0.004] emerged as significantly different from HC after adjusting for covariates in BLR. Notably, adults with IIM were more predisposed to retinal abnormalities [21 (57%) vs. 1 (16%), p=0.068], especially attenuation of vessels [14(38%) vs. 0(0), p=0.067] than jIIM. However, no difference was found in retinal features amongst the subtypes of adult IIM, nor did they correlate with MDAAT, MDI, or HAQ-DI. Conclusion: Retinal microvasculopathy and diminution of vision occur in nearly one-third to half of the patients with IIM. Microvasculopathy occurs across subtypes of IIM, and more so in adults, calling for further investigation as a surrogate for damage assessment and potentially even systemic vascular health.

Keywords: idiopathic inflammatory myopathies, vascular health, retinal microvasculopathy, arterial attenuation

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Authors: K. B. Chathyushya, M. Shiva Prakash, R. Hemalatha

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Introduction: Gastrointestinal (GI) tract has a number of microorganisms (microbiota) that influences the host’s health. The imbalance in the gut microbiota, which is also called as gut dysbiosis, affects human health which causes various metabolic, inflammatory, and infectious diseases. Probiotics play an important role in reinstating the gut balance. Probiotics are involved in the maintenance of healthier gut microbiota and have also been identified as effective adjuvants in insulin resistance therapies. Methods: This paper systematically reviews different randomized, controlled, blinded trials of probiotics for the treatment of various diseases along with the therapeutic or prophylactic properties of probiotic bacteria in different metabolic, inflammatory, infectious and anxiety-related disorders. Conclusion: The present review summarises that probiotics have some considerable effect in the management of various diseases, however, the benefits are strain specific, although more clinical trials are need to be carried out with different probiotic and symbiotic combinations as some probiotics have broad spectrum of benefits and few with specific activity

Keywords: life style diseases, cognition, health, gut dysbiosis, probiotics

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Authors: Faraj M. Elkhatri, Hana Ellafi

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In recent years, there has been a growing recognition of the potential of marine-based functional foods and combination therapies in promoting a healthy lifestyle and exploring their effectiveness in preventing or treating diseases. The combination of marine bioactive compounds or extracts offers synergistic or enhancement effects through various mechanisms, including multi-target actions, improved bioavailability, enhanced bioactivity, and mitigation of potential adverse effects. Both the green-lipped mussel (GLM) and fucoidan derived from brown seaweed are rich in bioactivities. These two, mussel and fucoidan, have not been previously formulated together. This study aims to combine GLM oil from Perna canaliculus with low molecular weight fucoidan (LMWF) extracted from Undaria pinnatifida to investigate the unique mixture’s anti-inflammatory and antioxidant properties. The cytotoxicity of individual compounds and combinations was assessed using the MTT assay in (THP-1 and RAW264.7) cell lines. The anti-inflammatory activity of mussel-fucoidan was evaluated by treating LPS-stimulated human monocyte and macrophage (THP1-1) cells. Subsequently, the inflammatory cytokines released into the supernatant of these cell lines were quantified via ELISA. Antioxidant activity was determined by using the free radical scavenging assay (DPPH). DPPH assay demonstrated that the radical scavenging activity of the combinations, particularly at concentrations exceeding 1 mg/ml, showed a significantly higher percentage of inhibition when compared to the individual component. This suggests an enhancement effect when the two compounds are combined, leading to increased antioxidant activity. In terms of immunomodulatory activity, the individual compounds exhibited distinct behaviors. GLM oil displayed a higher ability to suppress the cytokine TNF- compared to LMWF. Interestingly, the LMWF fraction, when used individually, did not demonstrate TNF- suppression. However, when combined with GLM, the TNF- suppression (anti-inflammatory) activity of the combination was better than GLM or LWMF alone. This observation underscores the potential for enhancement interactions between the two components in terms of anti-inflammatory properties. This study revealed that each individual compound, LMWF, and GLM, possesses unique and notable bioactivity. The combination of these two individual compounds results in an enhancement effect, where the bioactivity of each is enhanced, creating a superior combination. This suggests that the combination of LMWF and GLM has the potential to offer a more potent and multifaceted therapeutic effect, particularly in the context of antioxidant and anti-inflammatory activities. These findings hold promise for the development of novel therapeutic interventions or supplements that harness the enhancement effects.

Keywords: formation damage, porosity loses, pore throat, quartz cement

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Authors: Akshay Patil

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Objective: Mediation analysis identifies causal pathways by testing the relationships between the NCR, the OS, and an intermediate variable that mediates the relationship between the Nimotuzumab-cisplatin-radiation (NCR) and OS. Introduction: In randomized controlled trials, the primary interest is in the mechanisms by which an intervention exerts its effects on the outcomes. Clinicians are often interested in how the intervention works (or why it does not work) through hypothesized causal mechanisms. In this work, we highlight the value of understanding causal mechanisms in randomized trial by applying causal mediation analysis in a randomized trial in oncology. Methods: Data was obtained from a phase III randomized trial (Subgroup of HPVNOCP). NCR is reported to significantly improve the OS of patients locally advanced head and neck cancer patients undergoing definitive chemoradiation. Here, based on trial data, the mediating effect of NCR on patient overall survival was systematically quantified through progression-free survival(PFS), disease free survival (DFS), Loco-regional failure (LRF), and the disease control rate (DCR), Overall response rate (ORR). Effects of potential mediators on the HR for OS with NCR versus cisplatin-radiation (CR) were analyzed by Cox regression models. Statistical analyses were performed using R software Version 3.6.3 (The R Foundation for Statistical Computing) Results: Effects of potential mediator PFS was an association between NCR treatment and OS, with an indirect-effect (IE) 0.76(0.62 – 0.95), which mediated 60.69% of the treatment effect. Taking into account baseline confounders, the overall adjusted hazard ratio of death was 0.64 (95% CI: 0.43 – 0.96; P=0.03). The DFS was also a significant mediator and had an IE 0.77 (95% CI; 0.62-0.93), 58% mediated). Smaller mediation effects (maximum 27%) were observed for LRF with IE 0.88(0.74 – 1.06). Both DCR and ORR mediated 10% and 15%, respectively, of the effect of NCR vs. CR on the OS with IE 0.65 (95% CI; 0.81 – 1.08) and 0.94(95% CI; 0.79 – 1.04). Conclusion: Our findings suggest that PFS and DFS were the most important mediators of the OS with nimotuzumab to weekly cisplatin-radiation in HPVNOCP.

Keywords: mediation analysis, cancer data, survival, NCR, HPV negative oropharyngeal

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Authors: Milad Gholizadeh

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Asthma and chronic obstructive pulmonary disease (COPD) are very shared inflammatory diseases of the airlines. They togethercause airway tapering and are cumulative in occurrence throughout the world, imposing huge burdens on health care. It is currently recognized that some asthmatic inflammation is neutrophilic, controlled by the TH17 subset of helper T cells, and that some eosinophilic inflammation is controlled by type 2 innate lymphoid cells (ILC2 cells) temporary together with basophils. Patients who have plain asthma or are asthmatic patients who smoke with topographies of COPD-induced inflammation and might advantage from treatments targeting neutrophils, countingmacrolides, CXCR2 antagonists, phosphodiesterase 4 inhibitors, p38 mitogen-activating protein kinase inhibitors, and antibodies in contradiction of IL-1 and IL-17.Viral and bacterial infections, not only reason acute exacerbations of COPD, but also intensify and continue chronic inflammation in steady COPD through pathogen-associated molecular patterns. Present treatment plans are absorbed on titration of inhaled therapies such as long-acting bronchodilators, with cumulative interest in the usage of beleaguered biologic therapies meant at the underlying inflammatory devices. Educationssuggest that the mucosal IgA reply is abridged in COPD, and a lacking conveyance of IgA across the bronchial epithelium in COPD has been recognized, perhaps involving neutrophil proteinases, which may damage the Ig receptor mediating this transepithelialdirection-finding. Future instructions for investigation will emphasis elucidating the diverse inflammatory signatures foremost to asthma and chronic obstrucive, the development of reliable analytic standards and biomarkers of illness, and refining the clinical organization with an eye toward targeted therapies.

Keywords: imminology, asthma, COPD, CXCR2 antagonists

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Authors: Hager Elsheikh, Matthias Sendler, Juliana Glaubnitz

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In pancreatitis, an inflammatory reaction occurs in the pancreatic secretory cells due to premature activation of proteases, leading to pancreatic self-digestion and necrotic cell death of acinar cells. Acute pancreatitis in patients is characterized by a severe immune reaction that could lead to serious complications, such as organ failure or septic shock, if left untreated. Chronic pancreatitis is a recurrence of episodes of acute pancreatitis resulting in a fibro-inflammatory immune response, in which the type 2 immune response is primarily driven by AAMs in the pancreas. One of the most important signaling pathways for M2 macrophage activation is the IL-4/STAT6 pathway. Pancreatic fibrosis is induced by the hyperactivation of pancreatic stellate cells by dysregulation in the inflammatory response, leading to further damage, autodigestion and possibly necrosis of pancreatic acinar cells. The aim of this research is to investigate the effect of STAT6 knockout in disease severity and development of fibrosis wound healing in the presence of different macrophage populations, regulated by the type 2 immune response, after inducing chronic and/or acute pancreatitis in mice models via cerulean injection. We further investigate the influence of the JAK/STAT6 signaling pathway on the balance of fibrosis and regeneration in STAT6 deficient and wild-type mice. The characterization of resident and recruited macrophages will provide insight into the influence of the JAK/STAT6 signaling pathway on infiltrating cells and, ultimately, tissue fibrosis and disease severity.

Keywords: acute and chronic pancreatitis, tissue regeneration, macrophage polarization, Gastroenterology

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Authors: H. Sebai, M. A. Jabria, D. Wannes, H. Tounsi, L. Marzouki

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We aimed in the present study to investigate the protective effects of Tunisian Rosa canina aqueous extract (RCAE) against ethanol-induced gastric ulceration and oxidative stress in a rat model. In this respect, adult male Wistar rats were used and divided into six groups of ten each: control, EtOH, EtOH plus various doses of RCAE, EtOH plus famotidine and EtOH + gallic acid. Phytochemical and biochemical analysis were performed using colorimetric methods. We found that RCAE is rich in total polyphenols, total flavonoids, and condensed tannins, and exhibited an importance in vitro antioxidant activity on 2,2-diphenyl-1-picrylhydrazyl (DPPH) radical. In vivo, the results showed that oral administration of EtOH caused macroscopic and histological changes in gastric mucosa. These injuries are accompanied by an oxidative stress status as assessed by an increase of lipid peroxidation as well as a decrease of antioxidant enzyme activities such as superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx). Alcohol intoxication also induced intracellular mediators deregulation as assessed by an increase of hydrogen peroxide (H2O2), calcium and free iron levels in gastric mucosa. More, importantly, RCAE pretreatment reversed all macroscopic, histological and biochemical changes induced by EtOH administration. In conclusion, we suggest that RCAE has potent protective effects on acute ethanol-induced gastric ulceration related in part in part its antioxidant properties and its opposite effect on intracellular mediators. Indeed, Rosa canina can be offered as a food additive to protect against alcohol consumption-induced gastric and oxidative damage.

Keywords: alcohol, antioxidant properties, food additive, gastric ulceration, rat model, Rosa canina

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Authors: Christolyn Raj, Lewis Levitz

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Introduction: Two cases of late presentation ( > five years ) of bilateral pseudophakic macula edema related to oral tyrosine kinase inhibitors are described. These cases are the first of their type in the published literature. A review of ocular inflammatory complications of tyrosine kinase inhibitors in the current literature is explored. Case Presentations(s): Case 1 is an 83-year-old female who has been stable on Ibrutinib (Imbruvica ®) for chronic lymphocytic leukemia (CLL). She presented with bilateral blurred vision from severe cystoid macula edema seven years following routine cataract surgery. She was treated with intravitreal steroids with complete resolution without relapse. Case 2 is a 76-year-old female who was on therapy for polycythemia vera with Ruxolitinib (Jakafi®). She presented with bilateral blurred vision from mild cystoid macula edema six years following routine cataract surgery. She responded well to topical steroids without relapse. In both cases, oral tyrosine kinase inhibitor agents were presumed to be the underlying cause and were ceased. Over the last five years, there have been increasing reports in the literature of the inflammatory effects of tyrosine kinase inhibitors on the retina, uvea and optic nerve. Conclusion: Late presentation of pseudophakic macula edema following routine cataract surgery is rare. Such presentations should prompt investigation of the chronic use of systemic medications, especially oral kinase inhibitors. Patients who must remain on these agents require ongoing ophthalmologic assessment in view of their long-term inflammatory side effects.

Keywords: macula edema, oral kinase inhibitors, retinal toxicity, pseudo-phakia

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Authors: Stefanache Stefania, Ioana R. Podina

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Background: Embodied Conversational Agents (ECAs) are revolutionizing education and healthcare by offering cost-effective, adaptable, and portable solutions. Research on the Uncanny Valley effect (UVE) involves various embodied agents, including ECAs. Achieving the optimal level of anthropomorphism, no consensus on how to overcome the uncanniness problem. Objectives: This systematic review aims to identify the user characteristics, agent features, and context factors that influence the UVE. Additionally, this review provides recommendations for creating effective ECAs and conducting proper experimental studies. Methods: We conducted a systematic review following the PRISMA 2020 guidelines. We included quantitative, peer-reviewed studies that examined human-ECA interaction. We identified 17,122 relevant records from ACM Digital Library, IEE Explore, Scopus, ProQuest, and Web of Science. The quality of the predictors, mediators, and moderators adheres to the guidelines set by prior systematic reviews. Results: Based on the included studies, it can be concluded that females and younger people perceive the ECA as more attractive. However, inconsistent findings exist in the literature. ECAs characterized by extraversion, emotional stability, and agreeableness are considered more attractive. Facial expressions also play a role in the UVE, with some studies indicating that ECAs with more facial expressions are considered more attractive, although this effect is not consistent across all studies. Few studies have explored contextual factors, but they are nonetheless crucial. The interaction scenario and exposure time are important circumstances in human-ECA interaction. Conclusions: The findings highlight a growing interest in ECAs, which have seen significant developments in recent years. Given this evolving landscape, investigating the risk of the UVE can be a promising line of research.

Keywords: human-computer interaction, uncanny valley effect, embodied conversational agent, systematic review

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Authors: Fernanda Gonçalves, Karla Alcântara, Vanessa Moura, Patrícia Nolasco, Jorge Kalil, Maristela Hernandez

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Introduction: Atherosclerosis is a chronic disease where two striking features are observed: retention of lipids and inflammation. Understanding the interaction between immune cells and lipoproteins involved in atherogenesis are urgent challenges, since cardiovascular diseases are the leading cause of death worldwide. Macrophages are critical to the development of atherosclerotic plaques and in the perpetuation of inflammation in these lesions. These cells are also directly involved in unstable plaque rupture. Recently different populations of macrophages are being identified in atherosclerotic lesions. Although the presence of M2 macrophages (macrophages activated by the alternative pathway, eg. The IL-4) has been identified, the function of these cells in atherosclerosis is not yet defined. M2 macrophages have a high endocytic capacity, they promote remodeling of tissues and to have anti-inflammatory activity. However, in atherosclerosis, especially unstable plaques, severe inflammatory reaction, accumulation of cellular debris and intense degradation of the tissue is observed. Thus, it is possible that the M2 macrophages have altered function (phenotype) in atherosclerosis. Objective: Our aim is to evaluate if the presence of oxidized LDL alters the phenotype and function of M2 macrophages in vitro. Methods: For this, we will evaluate whether the addition of lipoprotein in M2 macrophages differentiated in vitro with IL -4 induces 1) a reduction in the secretion of anti-inflammatory cytokines (CBA and ELISA), 2) secretion of inflammatory cytokines (CBA and ELISA), 3) expression of cell activation markers (Flow cytometry), 4) alteration in gene expression of molecules adhesion and extracellular matrix (Real-Time PCR) and 5) Matrix degradation (confocal microscopy). Results: In oxLDL stimulated M2 macrophages cultures we did not find any differences in the expression of the cell surface markers tested, including: HLA-DR, CD80, CD86, CD206, CD163 and CD36. Also, cultures stimulated with oxLDL had similar phagocytic capacity when compared to unstimulated cells. However, in the supernatant of these cultures an increase in the secretion of the pro-inflammatory cytokine IL-8 was detected. No significant changes where observed in IL-6, IL-10, IL-12 and IL-1b levels. The culture supernatant also induced massive extracellular matrix (produced by mouse embryo fibroblast) filaments degradation. When evaluating the expression of 84 extracellular matrix and adhesion molecules genes, we observed that the stimulation of oxLDL in M2 macrophages decreased 47% of the genes and increased the expression of only 3% of the genes. In particular we noted that oxLDL inhibit the expression of 60% of the genes constituents of extracellular matrix and collagen expressed by these cells, including fibronectin1 and collagen VI. We also observed a decrease in the expression of matrix protease inhibitors, such as TIMP 2. On the opposite, the matricellular protein thrombospondin had a 12 fold increase in gene expression. In the presence of native LDL 90% of the genes had no altered expression. Conclusion: M2 macrophages stimulated with oxLDL secrete the pro-inflammatory cytokine IL-8, have an altered extracellular matrix constituents gene expression, and promote the degradation of extracellular matrix. M2 macrophages may contribute to the perpetuation of inflammation in atherosclerosis and to plaque rupture.

Keywords: atherosclerosis, LDL, macrophages, m2

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Authors: Sevil Arabaci Tamer, Gonul Gurol, Ibrahim Tekeoglu, Halil Harman, Ihsan Hakki Ciftci

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Neuroserpin (NSP) is a serine protease inhibitor and member of the serpin family. It is expressed in developing and adult nervous systems, and acts as an inhibitor of protease tissue plasminogen activator (tPA) and a regulator of neuronal growth and plasticity. Also NSP displays anti-inflammatory activity. But, its role in rheumatoid arthritis had never been studied before. So, the aim of the present study was to investigate the effect of neuroserpin in patients with RA. A total of 50 frozen (-20 ºC) serum samples 40 of them belonged to patients with RA, and 10 sample belonged to healthy subjects, were enrolled prospectively. We used DAS-28 to evaluate disease activity. The following clinical data gathered from the original patients' charts. Serum neuroserpin levels were measured by enzyme-linked immunosorbent assay. Our preliminary study results demonstrate, for the first time, that NSP levels are significantly different in RA patients relative to healthy subjects (P = 0.014). So, NSP contribute to pathological condition of RA. Thus, we believe that serum NSP levels can be as a marker in patients with RA. However other inflammatory diseases should be further investigated.

Keywords: neuroserpin, rheumatoid arthritis, tPA, tPA inhibitor

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Authors: Chanya Inprasit, Yi-Wen Lin

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Inflammation causes changes of peripheral and central nervous system properties, affecting both neuronal and non-neuronal cells, resulting in inflammatory pain. Acupoint injection (AI) was developed in the 1950s and has been widely used for relieving pain. It is an acupoint-stimulating technique that utilizes anatomically based meridians derived from Chinese medicine theory. AI has been accepted as an effective treatment and is thought to display superior results when compared to traditional acupuncture methods. However, the mechanism of AI needs to be ratified by more scientific evidence in order to support the theory and its therapeutic development. In this study, we explored the effect of AI on the comorbidity of chronic pain and depression. Mice hindpaw was injected by complete Freund’s adjuvant (CFA) to induce the condition of chronic pain. Measurements of mechanical and thermal hyperalgesia and depression-like behavior were analyzed. The results indicated a positive tendency to AI treatment. The comorbidity of chronic pain and depression was investigated with relation to transient receptor potential V1 (TRPV1) mechanism through the use of TRPV1 gene deletion. The expression of nociceptors such as voltage-gated sodium channels (Navs) or TRPV1, was significantly down-regulated by AI. The expression of inflammation-activated molecules: astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, and related kinases, were reversed by AI in both the peripheral and central nervous system. Taken together, these data provided a detailed molecular mechanism of AI-induced analgesia and anti-inflammatory properties. This finding may be utilized for clinical practice to treat chronic pain and depression comorbidity.

Keywords: inflammatory pain, acupoint injection, TRPV1, GFAP, S100B

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Authors: Yara Mohamed Taha, Mohamed Ali El Desouky, Heba Kamal Abdel Hakim, Maha Hanafy Mahmoud

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Hepatotoxicity due to drugs and toxic chemicals constitutes a crucial health problem nowadays. Medicinal plants are widely used recently for protecting against many liver disorders and inflammatory conditions. This study aims to evaluate hepatoprotective impact of green tea extract (GTE), rosemary extract (RE) and rosmarinic acid (RA) against hepatotoxins; ferric nitrilotriacetate (Fe-NTA) and diethylnitrosamine (DEN) in rats. Five groups of male Wistar rats were included; one control negative, while the other groups were treated intraperitoneally with DEN as 160 mg.kg-1 b.w. on 15th day and Fe-NTA as 5 mg.kg-1 b.w. on 33rd day. One of them was control positive. The other three groups were pre-administered with daily protective oral doses of either 200 mg.kg-1 b.w. of RE or 1 g.kg- 1 b.w. of GTE or 50 mg.kg-1 b.w. of RA two weeks prior to DEN exposure and continued till the end of the experimental period. The obtained data revealed a highly significant increase of MDA, 8-OHdG, DNA damage percent, a significant depletion of GSH and elevated Gr-1 protein expression in hepatocytes with liver tissue histopathological changes of rats exposed to DEN+Fe-NTA. Pre-administration of protective doses of RE, GTE and RA to DEN+Fe-NTA treated rats could normalize the altered biochemical, histopathological and immunohistochemical parameters. In conclusion, RE, GTE and RA showed a hepatoprotective effect against liver toxicity induced by DEN+Fe-NTA, with the best antioxidant and anti-inflammatory impact were for RA and GTE. Therefore, the current study declared that rosemary, green tea and products enriched with rosmarinic acid should be involved daily in diet of people who are exposed to chemicals and environmental toxins to protect themselves from hepatotoxicity.

Keywords: hepatotoxicity, diethylnitrosamine and ferric nitrilotriacetate, rosemary extract (RE), green tea extract (GTE), rosmarinic acid (RA)

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