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1

Hosseini, Azar, Vafa Baradaran Rahimi, Hassan Rakhshandeh, and Vahid Reza Askari. "Nigella sativa Oil Reduces LPS-Induced Microglial Inflammation: An Evaluation on M1/M2 Balance." Evidence-Based Complementary and Alternative Medicine 2022 (June 14, 2022): 1–11. http://dx.doi.org/10.1155/2022/5639226.

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Objectives. The immune system plays a critical defence role against infections, injuries, and carcinogenic stimuli. As the macrophages of the brain resides in the innate immune system, microglia and their polarisation (M1/M2) play regulatory roles in inflammation in CNS, such as Parkinson’s, Alzheimer’s, dementia complex, and multiple sclerosis. Nigella sativa belongs to the Ranunculaceae family and has different anti-inflammatory and antioxidant effects. We conducted this study to evaluate the anti-inflammatory and protective properties of N. sativa oil (NSO) on the microglial cells and their polarisation (M1/M2) in the presence of LPS as a model of neuroinflammation. Methods. The protective effects of NSO (10–40 µg/ml) were studied on the LPS-induced microglial cells, and the levels of tumour necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-6, prostaglandin E2 (PGE2), and IL-10 were evaluated using both ELISA and gene expression methods. The levels of cyclooxygenase-2 (COX-2), inducible NOS (iNOS), and arginase-1 (Arg1) were also evaluated using the real-time PCR method. In addition, nitrite oxide (NO) and urea were measured using biochemical methods. Results. NSO decreased LPS-induced toxicity at all doses ( P < 0.001). NSO (10–40 μg/ml) also significantly reduced the levels of TNF-α, PGE2, IL-1β, and IL-6 in the presence of LPS ( P < 0.01 to 0.001). Pretreatment with NSO attenuated the levels of iNOS but increased Arg1 ( P < 0.001). The ratio of iNOS/Arg1 was also decreased in the presence of NSO ( P < 0.001) than that of the LPS group ( P < 0.001). Conclusion. NSO attenuated LPS-induced inflammation and increased microglia’s anti-inflammatory status. These results may prove that NSO is potentially an immunomodulator for various neurodegenerative diseases by M1 phenotype dominancy, such as Alzheimer’s and Parkinson’s diseases.
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2

Gvozdeva, Olga V., Alexey A. Belogurov, Ekaterina S. Kuzina, Alexander G. Gabibov, Mariya I. Meschaninova, Alya G. Ven'yaminova, Marina A. Zenkova, Valentin V. Vlassov, and Elena L. Chernolovskaya. "Modified siRNA effectively silence inducible immunoproteasome subunits in NSO cells." Biochimie 125 (June 2016): 75–82. http://dx.doi.org/10.1016/j.biochi.2016.02.015.

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3

Rizk, Fatma H., Marwa A. A. Ibrahim, Marwa M. Abd-Elsalam, Nema A. Soliman, and Sherief M. Abd-Elsalam. "Gastroprotective effects of montelukast andNigella sativaoil against corticosteroid-induced gastric damage: they are much more than antiasthmatic drugs." Canadian Journal of Physiology and Pharmacology 95, no. 6 (June 2017): 714–20. http://dx.doi.org/10.1139/cjpp-2016-0374.

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Corticosteroids are used to treat a variety of diseases like bronchial asthma. However, long-term corticosteroids have a gastric ulcerogenic potential. Montelukast (MTK) and Nigella sativa oil (NSO) are used in treatment of bronchial asthma. Previous studies showed that MTK and NSO had gastroprotective effects in other models of gastric ulcer. The present study assesses synergistic gastroprotective effects of both drugs in dexamethasone (DXM)-induced gastric damage. Fifty male rats were divided into 5 groups: normal control (I), DXM group (II), MTK + DXM group (III), NSO + DXM group (IV), MTK + NSO + DXM group (V). After 7 days, stomachs were removed for biochemical analysis and histological examinations. Significant increases in malondialdehyde (MDA) level, superoxide dismutase (SOD) activity, myeloperoxidase (MPO) activity, and proliferating cell nuclear antigen (PCNA) positive cells, with significant decreases in mucus secretion were detected in DXM-treated group compared with group I. Meanwhile, significant decreases of MDA level, MPO activity, and PCNA positive cells and significant increases in mucus secretion were detected in treated groups compared with group II. SOD activity significantly decreased in group V compared with group II. We could conclude that administration of either MTK or NSO or both with DXM counteracts DXM-induced gastric lesions.
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4

Madkour, DA, MM Ahmed, SH Orabi, M. Alkafafy, R. Korany, and HK Khalifa. "Emamectin Benzoate-Induced Hepatotoxicity in Rats with Special Reference to Protective Potential of Nigella sativa Oil." Journal of the Hellenic Veterinary Medical Society 73, no. 3 (November 9, 2022): 4607–18. http://dx.doi.org/10.12681/jhvms.28100.

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This study was designed to explore the hepatotoxicity of emamectin in male rats and the possible effect of Nigella sativa oil (NSO) in ameliorating this. Twenty-eight male rats were used in this study. They were divided into four groups, Control group: rats orally administered distilled water; NSO group: rats administered NSO orally; EMB group: rats administered emamectin benzoate orally; and EMB+NSO group: rats orally co-administered NSO with EMB, with the administrations being performed every other day for 6 weeks. Body weight was measured, liver alanine aminotransferase (ALT), aspartate aminotransferase (AST), and alkaline phosphatase (ALP) activities were determined, and total protein and albumin levels were recorded. Histopathological examination of the liver was also performed, along with caspase-3 and TNF-α immunostaining of liver tissue. EMB treatment resulted in decreased body weight, while the co-administration of NSO modulated the EMB-induced alterations in body weight. There were also increases in the activities of serum ALT, AST, and ALP and decreases in total protein and albumin levels in the EMB group. Co-treatment with NSO significantly reduced serum ALT, AST, and ALP and improved total protein and albumin levels. Histopathological examination of the liver in the EMB group revealed the presence of different histopathological alterations that were improved by the co-administration of NSO. Immunostaining of caspase-3 and TNF-α in the liver revealed strong expression in the EMB-treated group. Meanwhile, the EMB+NSO group showed weak positivity for immunoreactive cells.
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5

Hammouda, Souha, Imen Ghzaiel, Pol Picón-Pagès, Wiem Meddeb, Wided Khamlaoui, Sonia Hammami, Francisco J. Muñoz, Mohamed Hammami, and Amira Zarrouk. "Nigella and Milk Thistle Seed Oils: Potential Cytoprotective Effects against 7β-Hydroxycholesterol-Induced Toxicity on SH-SY5Y Cells." Biomolecules 11, no. 6 (May 27, 2021): 797. http://dx.doi.org/10.3390/biom11060797.

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Oxysterols are assumed to be the driving force behind numerous neurodegenerative diseases. In this work, we aimed to study the ability of 7β-hydroxycholesterol (7β-OHC) to trigger oxidative stress and cell death in human neuroblastoma cells (SH-SY5Y) then the capacity of Nigella sativa and Milk thistle seed oils (NSO and MTSO, respectively) to oppose 7β-OHC-induced side effects. The impact of 7β-OHC, associated or not with NSO or MTSO, was studied on different criteria: cell viability; redox status, and apoptosis. Oxidative stress was assessed through the intracellular reactive oxygen species (ROS) production, levels of enzymatic and non-enzymatic antioxidants, lipid, and protein oxidation products. Our results indicate that 7β-OHC (40 µg/mL) exhibit pr-oxidative and pro-apoptotic activities shown by a decrease of the antioxidant enzymatic activities and an increase of ROS production, lipid, and protein oxidation end products as well as nitrotyrosine formation and caspase 3 activation. However, under the pre-treatment with NSO, and especially with MTSO (100 µg/mL), a marked attenuation of oxidative damages was observed. Our study suggests harmful effects of 7β-OHC consisting of pro-oxidative, anti-proliferative, and pro-apoptotic activities that may contribute to neurodegeneration. NSO and especially MTSO showed potential cytoprotection against the cytotoxicity of 7β-OHC.
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6

Mosbah, Rachid, Mokhtar Ibrahim Yousef, Francesca Maranghi, and Alberto Mantovani. "Protective role of Nigella sativa oil against reproductive toxicity, hormonal alterations, and oxidative damage induced by chlorpyrifos in male rats." Toxicology and Industrial Health 32, no. 7 (November 25, 2014): 1266–77. http://dx.doi.org/10.1177/0748233714554675.

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This study is aimed at elucidating the possible protective effects of Nigella sativa oil (NSO) in alleviating the toxicity of chlorpyrifos (CPF) on reproductive performance in male rats. Animals were orally administered with NSO (1 ml/kg/day), CPF (20 mg/kg/day), and NSO + CPF every day for 4 weeks. Results showed that CPF decreased spermatid number, sperm count, daily sperm production, and sperm motility while increased dead sperm and abnormal sperm compared with the control. Also the levels of testosterone, thyroxine levels, steroidogenic enzyme 17-ketosteroid reductase, body weight, food intake, and relative weight of reproductive organs were decreased. Thiobarbituric acid reactive substances were increased, while glutathione (GSH) and antioxidant enzymes were decreased in plasma and testes of rats treated with CPF. Histopathological examination of testes showed a decrease in the number of seminiferous tubules, form shrinkage, enlargement of the connective tissue and gametogenic changes in germ cells of rats treated with CPF. NSO alone increased testosterone, semen characteristics, GSH, and antioxidant enzymes and decreased the levels of free radicals. Furthermore, the presence of NSO with CPF alleviates its toxic effects. Our results indicated that NSO can improve semen picture and moderate CPF-induced reproductive toxicity.
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7

Peakman, Timothy C., Jennifer Worden, Robert H. Harris, Helen Cooper, John Tite, Martin J. Page, Dirk R. Gewert, Michelle Bartholemew, James S. Crowe, and Sara Brett. "Comparison of expression of a humanized monoclonal antibody in mouse NSO myeloma cells and Chinese Hamster Ovary cells." Human Antibodies 5, no. 1-2 (March 1, 1994): 65–74. http://dx.doi.org/10.3233/hab-1994-51-209.

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8

Imam, Aminu, Christianah Oyegbola, Maryam Busari, Rukayat Jaji-Sulaimon, Abdulmusawwir Alli-Oluwafuyi, Akeem Okesina, Adam Afodun, and Moyosore Ajao. "Nigella sativa Oil Preserved Anxiety-Like, Motor and Memory Related Behaviours and Neuronal Integrity in Dichlorvos Induced Acetyl Cholinesterase Inhibitions in Rats." NIgerian Journal of Neuroscience 12, no. 3 (December 31, 2021): 84–91. http://dx.doi.org/10.47081/njn2021.12.3/002.

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Organophosphates are irreversible cholinesterase (ChE) inhibitors with neurological consequences, and there is not yet an effective antidote. Here, we investigated the effects of Nigella sativa oil (NSO) on the ChE inhibition, neurobehavioural and histopathological changes following dichlorvos (DDVP) ingestions in rats. Thirty-two male Wistar rats were randomised into four groups, receiving 1 ml/kg of normal saline, 8.8 mg/kg of DDVP, 8.8 mg/kg of DDVP and 1 ml/kg of NSO, and 1 ml/kg of NSO only respectively, for 14 consecutive days. Locomotor, anxiety-like behaviours and spatial working memory were assessed on the 14th day, using open field (OF), Y-maze and modified elevated plus maze paradigms. The rats were euthanized on the 15th day and the brains excised; three brains were fixed for histopathology, and the other five prepared for biochemical analysis of acetyl cholinesterase (AChE). DDVP exposure caused significant reductions in frontal, amygdala and cerebella AChE activity, spontaneous alternations, line crossing and rearing frequencies and time in centre square, and caused increase in freezing period, transfer latency and necrotic-like cells. NSO intervention was able to reverse DDVP effects on AChE activities, explorative, locomotor, anxiety and spatial memory behaviours in co-exposed rats. It also preserved the histological integrity of the investigated brain regions. It can be concluded that NSO, may be potent against organophosphates induced neurotoxicity and their neurobehavioural consequences through the modulation of AChE activities.
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9

Barlianto, Wisnu, Maria Rachmawati, Muhammad Irawan, and Desy Wulandari. "Effects of Nigella sativa oil on Th1/Th2, cytokine balance, and improvement of asthma control in children." Paediatrica Indonesiana 57, no. 5 (October 31, 2017): 223. http://dx.doi.org/10.14238/pi57.5.2017.1399.

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Background Asthma is a chronic inflammatory disease of the airways characterized by involvement of a variety of inflammatory cells. Asthma is associated with imbalances between Th1/Th2 cells and their characteristic cytokine profiles. Nigella sativa is a plant that possesses immunomodulatory and anti-inflammatory properties.Objective To investigate the potential anti-asthmatic effect of Nigella sativa oil on Th1/Th2 cells, IFN-ɣ/IL-4 cytokines, and improvement of asthma control.Methods Children aged 6-15 years with asthma in Dr. Saiful Anwar Hospital, Malang, were enrolled in this study. All patients were treated based on standard treatment guidelines for asthma. Nigella sativa oil (NSO) was given per oral as supplementary treatment at a dose of 15-30 mg/kg/day for 8 weeks, in a randomized, single-blind, controlled trial. Peripheral Th1 and Th2 cells were counted by flow cytometry and IFN-ɣ and IL-4 cytokines were measured by ELISA. Improvement of asthma control was assessed by the asthma control test (ACT) score.Results Twenty-eight patients completed the study, 14 in the NSO treatment group and 14 in standard treatment group. No significant differences were found in the number of Th1 and Th2 cells, or in the Th1/Th2 ratio between groups after treatment (P=0.074, P=0.481, and P=0.265, respectively). Compared to the control, the NSO group showed a significant elevation of IFN-ɣ (P=0.046) and reduction of IL-4 (P=0.002). At the end of study, ACT score was not significantly different between groups (P=0.413).Conclusion Supplementation with Nigella sativa oil improves IFN-ɣ/IL-4 balance and asthma control in children with asthma.
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10

Barlianto, Wisnu, Maria Rachmawati, Muhammad Irawan, and Desy Wulandari. "Effects of Nigella sativa oil on Th1/Th2, cytokine balance, and improvement of asthma control in children." Paediatrica Indonesiana 57, no. 5 (January 5, 2018): 223. http://dx.doi.org/10.14238/pi57.5.2017.223-8.

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Background Asthma is a chronic inflammatory disease of the airways characterized by involvement of a variety of inflammatory cells. Asthma is associated with imbalances between Th1/Th2 cells and their characteristic cytokine profiles. Nigella sativa is a plant that possesses immunomodulatory and anti-inflammatory properties.Objective To investigate the potential anti-asthmatic effect of Nigella sativa oil on Th1/Th2 cells, IFN-ɣ/IL-4 cytokines, and improvement of asthma control.Methods Children aged 6-15 years with asthma in Dr. Saiful Anwar Hospital, Malang, were enrolled in this study. All patients were treated based on standard treatment guidelines for asthma. Nigella sativa oil (NSO) was given per oral as supplementary treatment at a dose of 15-30 mg/kg/day for 8 weeks, in a randomized, single-blind, controlled trial. Peripheral Th1 and Th2 cells were counted by flow cytometry and IFN-ɣ and IL-4 cytokines were measured by ELISA. Improvement of asthma control was assessed by the asthma control test (ACT) score.Results Twenty-eight patients completed the study, 14 in the NSO treatment group and 14 in standard treatment group. No significant differences were found in the number of Th1 and Th2 cells, or in the Th1/Th2 ratio between groups after treatment (P=0.074, P=0.481, and P=0.265, respectively). Compared to the control, the NSO group showed a significant elevation of IFN-ɣ (P=0.046) and reduction of IL-4 (P=0.002). At the end of study, ACT score was not significantly different between groups (P=0.413).Conclusion Supplementation with Nigella sativa oil improves IFN-ɣ/IL-4 balance and asthma control in children with asthma.
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11

Imam, Aminu, Barakat Oyindamola Salaudeen, Aboyeji Lukuman Oyewole, Asma'u Shehu Muhammad, Christianah Oyegbola, Rukayat Jaji-Sulaimon, Fatimo Ajoke Sulaimon, Adam Moyosore Afodun, and Moyosore Salihu Ajao. "Chlorpyrifos impaired cerebellar oxidative and cholinesterase activities in rats: Mitigating efficacy of Nigella sativa Oil." Nepal Journal of Neuroscience 18, no. 2 (June 1, 2021): 15–22. http://dx.doi.org/10.3126/njn.v18i2.34525.

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Background: Motor dysfunctions are some of the characteristic symptoms of organophosphate (OP) poisoning and they have been associated with decreased levels of cholinesterase inhibition within motor areas of the brain. Objectives: The current study aims to investigate the potential neuroprotective effects of Nigella sativa oil (NSO) in alleviating chlorpyrifos (CPF) induced toxicity in the cerebella and motor cortices of the rat brains using combined behavioural, biochemical and histochemical methods. Methods: Thirty-two rats were randomly divided into four groups (eight rats per group), exposed to 1ml/kg of normal saline, 14.9 mg/kg of CPF, 14.9 mg/kg of CPF plus 1ml/kg of NSO and 1ml/kg of NSO respectively for 14 consecutive days. The rats were each exposed to a single trial of the Open Field Test (OFT) on day 13 of the experiment. This experimental test measured locomotor activity levels (line crossing frequency (LCF)) and exploratory (rearing frequency (RF)) activities in the rats studied. The rats were euthanized on day 15 of the experiment and the brains were subsequently excised. The cerebella cortices of five brains were removed and homogenised to analyse for total reactive oxygen species (ROS), nitric oxide (NO) levels and acetylcholinesterase (AChE) activity. The motor and cerebella cortices from three other brains in each group were processed for histology (Nissl stain) and proliferative activity (Ki67 immunohistochemistry). Results: Rats exposed to CPF experienced a significant increase in cerebella NO and ROS levels, depletion in AChE activity, neurogenic cells loss and subsequent reduction in locomotor and exploratory behaviours respectively (LCF and RF). However, interventional treatment with NSO depleted markers of oxidative damage (NO and ROS), reduced AChE inhibition, preserved neurogenic (Ki67) cells distribution and motor functions. Conclusion: These results demonstrate the potential efficacy of NSO in OP poisoning and the roles of neurogenic and oxidative functions in the pathophysiology and treatment of motor dysfunction in OP neurotoxicity.
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Baszler, Timothy V., Terry F. McElwain, and Bruce A. Mathison. "Immunization of BALB/c Mice with Killed Neospora caninum Tachyzoite Antigen Induces a Type 2 Immune Response and Exacerbates Encephalitis and Neurological Disease." Clinical Diagnostic Laboratory Immunology 7, no. 6 (November 1, 2000): 893–98. http://dx.doi.org/10.1128/cdli.7.6.893-898.2000.

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ABSTRACT BALB/c mice were immunized subcutaneously with solubleNeospora caninum tachyzoite antigen (NSO) entrapped in nonionic surfactant vesicles (NISVs) or administered with Freund's complete adjuvant (FCA). Following virulent parasite challenge, groups of mice immunized with NSO and either NISVs or FCA had clinical neurological disease and increased numbers of brain lesions compared to groups of mice inoculated with FCA, NISVs, or phosphate-buffered saline (PBS) alone. Increased numbers of brain lesions were statistically significant only between mice immunized with NISV-NSO and NISV- or PBS-treated mice. Following parasite challenge, brain inflammatory infiltrates in all experimental and control groups of mice were relatively similar and consisted of compact infiltrates of macrophages admixed with various numbers of lymphoid cells. Increased brain lesions in NSO-immunized mice were associated with increased antigen-specific interleukin 4 (IL-4) secretion and increased IL-4:gamma interferon secretion ratios from splenocytes in vitro and increased antigen-specific immunoglobulin G1 (IgG1):IgG2a ratios in vivo. Thus, immunization with whole killed N. caninum antigen and either liposoidal or Freund's adjuvant induced a type 2 immune response that was associated with worsened disease. The present studies emphasize the need to identify specific N. caninum antigens or other delivery systems that will elicit protective immune responses to neosporosis.
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Rossmann, Cornelia, Nigel Sharp, Geoffrey Allen, and Dirk Gewert. "Expression and Purification of Recombinant, Glycosylated Human Interferon Alpha 2b in Murine Myeloma NSo Cells." Protein Expression and Purification 7, no. 4 (June 1996): 335–42. http://dx.doi.org/10.1006/prep.1996.0050.

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14

DiStefano, D. J., G. E. Mark, and D. K. Robinson. "Feeding of nutrients delays apoptotic death in fed-batch cultures of recombinant NSO myeloma cells." Biotechnology Letters 18, no. 9 (September 1996): 1067–72. http://dx.doi.org/10.1007/bf00129733.

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15

O'Mahony, A. M., G. C. O'Sullivan, J. O'Connell, T. G. Cotter, and J. K. Collins. "An immune suppressive factor derived from esophageal squamous carcinoma induces apoptosis in normal and transformed cells of lymphoid lineage." Journal of Immunology 151, no. 9 (November 1, 1993): 4847–56. http://dx.doi.org/10.4049/jimmunol.151.9.4847.

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Abstract An immunosuppressive factor produced by an esophageal squamous carcinoma cell line mediates profound irreversible suppression of in vitro proliferative responses of lymphoid cells. Exposure of activated normal PBL to the immune suppressive factor (ISF) resulted in the induction of an irreversible anergic state with apoptosis evident in 20% of those cells. Flow cytometric cell cycle analysis of mitogenically stimulated normal lymphocytes exposed to the ISF revealed that despite exhibiting full activation status (IL-2 production, IL-2R, and transferrin receptor expression) PBL were arrested at the G1/S interphase of the cell cycle. Transformed lymphoid cell lines, NSO and JURKAT, displayed morphologies characteristic of apoptosis within 24 h of exposure to the ISF. Flow cytometric cell cycle analysis of the JURKAT cells incubated with ISF revealed that &gt; 90% of these cells had undergone apoptosis within 24 h. Agarose gel electrophoresis of DNA extracted from the ISF-treated lymphoid cells resolved a DNA fragmentation pattern characteristic of apoptosis in both the NSO cells and to a lesser extent in the activated PBL exposed to the ISF but not in control cells. In JURKAT cells stimulated with anti-CD3 antibodies, Ca2+ mobilization was markedly enhanced in those cells exposed to ISF. Also, ISF independently induced a calcium flux in JURKAT cells. Induction of programmed cell death by ISF may account for the in vivo immune suppression local to the tumor site in squamous carcinoma of the esophagus.
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Rahman, AFM Towheedur, Md Saiful Islam, Md Hazrat Ali, AHM Khurshid Alam, Md Aziz Abdur Rahman, Md Golam Sadik, and Mamunur Rashid. "Nigella sativa Oil Potentiates the Effects of Pioglitazone on Long Term Alloxan-Induced Diabetic Rats." Bangladesh Pharmaceutical Journal 16, no. 2 (February 20, 2015): 143–51. http://dx.doi.org/10.3329/bpj.v16i2.22296.

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The present study was designed to investigate the effects of combination of Nigella sativa oil and pioglitazone on long-term alloxan-induced diabetic rats. In short-term (two weeks) alloxan-induced diabetic rats, N. sativa oil (NSO) reduced significant amount of glucose in blood, TC, TG and LDL-C and increased significant amount of HDL-C compared to diabetic rats. However, pathological changes of pancreas’s Islets of Langerhans were observed after long-term (four weeks) induction of alloxan in rats. Administration of NSO recovered Langerhans cells from shrinkage whereas pioglitazone displayed slight recovery. But the combination therapy showed complete recovery of Langerhans cells as compared with diabetic rats. Combination of drugs significantly reduced the TC, TG and LDL-C level as well as increased significant amount of HDL-C level to the normal level. Combination also increased DPPH free radical scavenging activity compared with diabetic rats. The results suggest that treatment with combination therapy was more effective than mono-therapy for preventing diabetes as N. sativa oil potentiates the effects of pioglitazone on long term alloxan-induced diabetic rats. DOI: http://dx.doi.org/10.3329/bpj.v16i2.22296 Bangladesh Pharmaceutical Journal 16(2): 143-151, 2013
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Zarrouk, Amira, Lucy Martine, Stéphane Grégoire, Thomas Nury, Wiem Meddeb, Emmanuelle Camus, Asmaa Badreddine, et al. "Profile of Fatty Acids, Tocopherols, Phytosterols and Polyphenols in Mediterranean Oils (Argan Oils, Olive Oils, Milk Thistle Seed Oils and Nigella Seed Oil) and Evaluation of their Antioxidant and Cytoprotective Activities." Current Pharmaceutical Design 25, no. 15 (August 19, 2019): 1791–805. http://dx.doi.org/10.2174/1381612825666190705192902.

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Background: The effects of vegetable oils on human health depend on their components. Therefore, their profiles of lipid nutrients and polyphenols were determined. Objective: To establish and compare the fatty acid, tocopherol, phytosterol and polyphenol profiles of Mediterranean oils: cosmetic and dietary argan oils (AO; Morocco: Agadir, Berkane); olive oils (OO; Morocco, Spain, Tunisia); milk thistle seed oils (MTSO; Tunisia: Bizerte, Sousse, Zaghouane); nigella seed oil (NSO). Methods: The biochemical profiles were determined by gas chromatography-flame ionization, high performance liquid chromatography and gas chromatography, coupled with mass spectrometry as required. The antioxidant and cytoprotective activities were evaluated with the KRL (Kit Radicaux Libres) and the fluorescein diacetate tests on nerve cells treated with 7-ketocholesterol (7KC). Results: The fatty acid profile revealed high linoleic acid (C18:2 n-6) content in AO, OO, MTSO and NSO. The highest levels of oleic acid (C18:1 n-9) were found in AO and OO. The tocopherol profile showed that Agadir AO contained the highest amount of α-tocopherol, also present at high level in MTSO and Tunisian OO; Berkane AO was rich in γ-tocopherol. The phytosterol profile indicated that β-sitosterol was predominant in the oils, except AO; spinasterol was only present in AO. Polyphenol profiles underlined that OO was the richest in polyphenols; hydroxytyrosol was only found in OO; few polyphenols were detected in AO. The oils studied have antioxidant activities, and all of them, except NSO, prevented 7KC-induced cell death. The antioxidant characteristics of AO were positively correlated with procatechic acid and compestanol levels. Conclusion: Based on their biochemical profiles, antioxidant and cytoprotective characteristics, AO, OO, and MTSO are potentially beneficial to human health.
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ERGEN, Nuri, and Halil TÜFEKÇİ. "Mammalian cell lines used in bioprocessing." Journal of Experimental and Clinical Medicine 39, no. 3 (August 30, 2022): 884–92. http://dx.doi.org/10.52142/omujecm.39.3.55.

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A various number of expressions and host systems are used in biologics manufacturing. The most commonly preferred systems are based on bacteria, yeast, mammalian cells, insect cells, and transgenic animals. A wide range of molecules, including insulin, mAbs, vaccines, and recombinant proteins, are produced using different host systems. Because of several reasons impacting the product quality and yield, mammalian cells are utilized. Moreover, mammalian cells are generally used in virus-based vaccine manufacturing. Chinese Hamster Ovary (CHO) is the most widely used cell line for high yield stable recombinant protein production, while Human Embryonic Kidney (HEK) is favoured for transient transfection low yield protein manufacturing, viral-based vaccine and gene and cell therapy-related vector production. Other mammalian cell lines such as NSO, Sp2.0, Vero, MRC-5 and PerC.6 are also used in both recombinant protein and virus productions. Multiple modifications are carried out on industrial cell lines to make them more suitable for high yield and high-quality protein production. Thanks to these alterations, high productivity and quality levels are achieved in the biotechnology industry.
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Edwards, A. M., F. Barredo, E. Silva, A. E. De Ioannes, and M. I. Becker. "Apoptosis Induction in Nonirradiated Human HL-60 and Murine NSO/2 Tumor Cells by Photoproducts of Indole-3-acetic Acid and Riboflavin." Photochemistry and Photobiology 70, no. 4 (1999): 645. http://dx.doi.org/10.1562/0031-8655(1999)070<0645:aiinhh>2.3.co;2.

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Edwards, A. M., F. Barredo, E. Silva, A. E. Ioannes, and M. I. Becker. "Apoptosis Induction in Nonirradiated Human HL-60 and Murine NSO/2 Tumor Cells by Photoproducts of lndole-3-acetic Acid and Riboflavin." Photochemistry and Photobiology 70, no. 4 (October 1999): 645–49. http://dx.doi.org/10.1111/j.1751-1097.1999.tb08264.x.

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21

Blair Zajdel, M. E., M. D. Barker, S. C. Dixon, and G. E. Blair. "The use of monoclonal antibodies to study the proteins specified by the transforming region of human adenoviruses." Biochemical Journal 225, no. 3 (February 1, 1985): 649–55. http://dx.doi.org/10.1042/bj2250649.

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Monoclonal antibodies against two of the proteins specified by one of the transforming genes (early region 1B) of human adenovirus type 2 have been produced and characterized. Two clones (RA1 and PA6), generated by fusion of mouse myeloma NSO cells with splenocytes from rats immunized with whole-cell lysates of an adenovirus-transformed rat cell line (F19), secreted antibodies against a 58 kDa protein. Another clone (DC1) produced antibodies against the same protein, and resulted from fusion of immune rat splenocytes with the rat myeloma Y3. Ag.1.2.3. Immunoprecipitation studies showed that all three antibodies recognized [35S]-methionine-labelled 58 kDa protein, and phosphorylated derivatives of the 58 kDa protein labelled with [32P]orthophosphate present in infected human cells. One clone (EC3) produced antibody against a 19 kDa protein also encoded by early region 1B, but not sharing sequence homology with 58 kDa. The identity of the 19 kDa protein recognized by the EC3 antibody was established by immunoprecipitation from lysates of labelled-infected cells and from products of cell-free translation directed by mRNA isolated from adenovirus 2-infected cells. Indirect immunofluorescent-antibody staining of infected human cells using the RA1 and EC3 antibodies revealed a nuclear location of the 58 kDa protein and a mainly cytoplasmic location of the 19 kDa protein.
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Astrakhantseva, I. V., L. S. Gladkova, E. A. Vasilenko, V. S. Tarabykin, M. S. Drutskaya, and S. A. Nedospasov. "NEW STRAIN OF MUTANT MICE CHARACTERIZED BY SELECTIVE RESISTANCE TO ONE OF TWO SEPTIC SHOCK PROTOCOLS." Russian Journal of Immunology 23, no. 1 (January 15, 2020): 27–34. http://dx.doi.org/10.46235/1028-7221-003-nso.

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More than 40 years ago ethyl nitrosoеurea was identified as a powerful mutagen for mammalian germ cells resulting in random point mutations in gamete DNA. This feature allowed the use of this mutagen for genetic studies on the mechanisms of various pathological and physiological processes in model organisms. In our study genome-wide mutagenesis in C3H mice by ethyl nitrosourea followed in generation F3 by selection of animals resistant to acute lethal hepatotoxicity caused by a combination of E. coli lipopolysaccharide (LPS) and D-galactosamine (D-gal). Tumor necrosis factor (TNF) is known to be a critical mediator of this pathology. Exposure to D-galactosamine increases sensitivity of hepatocytes to TNF leading to their necrosis and/or apoptosis. After double LPS/D-gal screening in F3 several mice resistant to LPS/D-gal-induced hepatotoxicity were identified, and became the founders of the corresponding “mutant” families. Using outcrossing to C57BL6 background followed by intercrossing, generations F5 and F7 were obtained. Among families of mutant animals only one family showed the resistance to the combination of LPS and D-gal, but sensitivity to TNF-D-galactosamine. This phenotype showed approximately Mendelian inheritance consistent with the recessive mutation hypothesis. This latter fact was confirmed by the sensitivity of mice from “heterozygous generations” (F4 and F6) to lethal LPS/Dgal hepatotoxicity. Primary bone marrow macrophages obtained from half of the mutant mice showed significantly reduced levels of TNF after LPS stimulation in vitro. At the same time, the serum TNF levels 1 hour after the administration of a non-lethal LPS dose did not differ in the mutant family mice and wild-type mice. These results implicate a recessive mutation either in innate TLR4-mediated signaling pathway, including proteins associated with LPS transfer, adapter molecules, components of kinase signaling cascades, transcription factors, or in enzymes involved in regulation of TLR4 cascades, such as components of the ubiquitin cycle, or in genomic regulatory sequences that control the expression of one of these genes, including the tnf gene.
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Wang, Jinghua, Brian Manick, Guoping Wu, and Vassili Kalabokis. "Immune modulation by butyrophilin 1A1 (BTN1A1)." Journal of Immunology 196, no. 1_Supplement (May 1, 2016): 199.1. http://dx.doi.org/10.4049/jimmunol.196.supp.199.1.

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Abstract The butyrophilins are B7-like T cell co-regulatory molecules. These molecules are of increasing interest in cancer immunotherapy as they may represent a novel subset of immune check-point regulators. In this study, we expressed the recombinant human butyrophilin 1A1 extracellular domain with a C terminal 6-His tag (BTN1A1) in NSO mouse myeloma cell line, and investigated the biological functions of the purified recombinant BTN1A1 protein in vitro. Human T cells were treated with plate-bound anti-CD3 and BTN1A1. The levels of multiple cytokines were measured in cell culture supernatants using R&D Systems Proteome Profiler™ Human Cytokine Array and confirmed by measuring individual cytokines using cytokine-specific Quantikine® ELISA kits. BTN1A1 significantly decreased T-cell derived cytokines such as IL-2, IL-21, IL-25, CD40L, and C5a, but not IFN-gamma. BTN1A1 also markedly inhibited anti-CD3-induced human T cell proliferation in a dose dependent manner. Furthermore, BTN1A1 showed binding to anti-CD3 activated, but not rest T cells. Moreover, recombinant human BTN1A1 inhibited p38 MAPK, CREB, and TOR Phosphorylation, suggesting BTN1A1 modulates TCR signaling through the p38 MAP kinase, CREB, and TOR pathways. Taken together, our data suggests that BTN1A1 acts as a co-inhibitory molecule to modulate T cells through an unknown receptor on the surface of T cells. BTN1A1 may be a potential target of immune check-point molecules for therapeutic purposes.
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Pilson, R. S., W. Levin, B. Desai, L. M. Reik, P. Lin, E. Korkmaz-Duffy, E. Campbell, J. Y. Tso, J. A. Kerwin, and J. Hakimi. "Bispecific humanized anti-IL-2 receptor alpha beta antibodies inhibitory for both IL-2- and IL-15-mediated proliferation." Journal of Immunology 159, no. 3 (August 1, 1997): 1543–56. http://dx.doi.org/10.4049/jimmunol.159.3.1543.

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Abstract Humanized anti-Tac (HAT) and Mik beta1 (HuMik beta 1) Abs directed at IL-2R alpha and IL-2R beta, respectively, inhibit IL-2 binding and biological activity and together act synergistically in vitro. The Abs have been used successfully in primate models of allograft rejection, graft-vs-host disease, and autoimmunity. We produced bifunctional humanized anti-IL-2R alpha beta Abs (BF-IgG) to combine the specificity of the two Abs into one entity by fusing HAT-producing NSO cells and HuMik beta 1-producing Sp2/0 cells. BF-IgG was purified using protein G-Sepharose affinity chromatography, followed by IL-2R alpha and IL-2R beta affinity chromatography and hydrophobic interaction chromatography. BF-IgG exhibited both anti-IL-2R alpha and anti-IL-2R beta specificities in binding assays. While the Ab binds the IL-2R with intermediate affinity (Kd = 2.82 nM), it does not inhibit IL-15 binding to its high affinity IL-15R. In Kit225/K6 (IL-2R alpha beta gamma+) cells, BF-IgG was 10-fold more potent than a HAT/HuMik beta 1 equimolar mixture in blocking IL-2-induced proliferation and, unexpectedly, was at least 65-fold more active than the mixture in blocking IL-15-induced proliferation. This dual inhibitory activity may be due to cross-linking of the IL-2R alpha and IL-2R beta, thus blocking IL-2 binding and possibly impeding the association of IL-2R beta with IL-15R. BF-IgG has potent immunosuppressant activities against both IL-2- and IL-15-mediated responses, and this antagonist could be more efficacious than HAT and/or HuMik beta 1 for the treatment of autoimmunity and the prevention of allograft rejection.
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Gasperini, Sofia, Sabrine Bilel, Veronica Cocchi, Matteo Marti, Monia Lenzi, and Patrizia Hrelia. "The Genotoxicity of Acrylfentanyl, Ocfentanyl and Furanylfentanyl Raises the Concern of Long-Term Consequences." International Journal of Molecular Sciences 23, no. 22 (November 19, 2022): 14406. http://dx.doi.org/10.3390/ijms232214406.

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Three fentanyl analogues Acrylfentanyl, Ocfentanyl and Furanylfentanyl are potent, rapid-acting synthetic analgesics that recently appeared on the illicit market of new psychoactive substances (NPS) under the class of new synthetic opioids (NSO). Pharmacotoxicological data on these three non-pharmaceutical fentanyl analogues are limited and studies on their genotoxicity are not yet available. Therefore, the aim of the present study was to investigate this property. The ability to induce structural and numerical chromosomal aberrations in human lymphoblastoid TK6 cells was evaluated by employing the flow cytometric protocol of the in vitro mammalian cell micronucleus test. Our study demonstrated the non-genotoxicity of Fentanyl, i.e., the pharmaceutical progenitor of the class, while its illicit non-pharmaceutical analogues were found to be genotoxic. In particular, Acrylfentanyl led to a statistically significant increase in the MNi frequency at the highest concentration tested (75 μM), while Ocfentanyl and Furanylfentnyl each did so at both concentrations tested (150, 200 μM and 25, 50 μM, respectively). The study ended by investigating reactive oxygen species (ROS) induction as a possible mechanism linked to the proved genotoxic effect. The results showed a non-statistically significant increase in ROS levels in the cultures treated with all molecules under study. Overall, the proved genotoxicity raises concern about the possibility of serious long-term consequences.
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Tu, Bailin, Robert N. Ziemann, Bryan C. Tieman, David J. Hawksworth, Joan Tyner, James Scheffel, Mary S. Pinkus, et al. "Generation and Characterization of Chimeric Antibodies against NS3, NS4, NS5, and Core Antigens of Hepatitis C Virus." Clinical and Vaccine Immunology 17, no. 6 (April 28, 2010): 1040–47. http://dx.doi.org/10.1128/cvi.00068-10.

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ABSTRACT Mouse-human chimeric antibodies (cAbs) against hepatitis C virus (HCV) core, NS3 (nonstructural), NS4, and NS5 antigens were developed as quality control (QC) reagents to replace the use of human sera/plasma for Abbott HCV immunoassays. The cAb retains the mouse monoclonal antibody (MAb) specificity and affinity but still reacts in the existing HCV assay format, which measures human anti-HCV immunoglobulin. Mouse heavy-chain (VH) and light-chain (VL) variable regions of anti-HCV core, NS3, NS4, and NS5 antigens were PCR amplified from hybridoma lines and then cloned with human IgG1 heavy-chain (CH) and light-chain (CL) constant regions, respectively. A single mammalian expression plasmid containing both heavy-chain and light-chain immunoglobulin genes was constructed and transfected into dihydrofolate reductase (DHFR)-deficient Chinese hamster ovary (CHO) cells. The transfected CHO cells were selected using hypoxanthine- and thymidine-free medium and screened by an enzyme immunoassay (EIA). The clone secreting the highest level of antibody was isolated from the CHO transfectants and further subcloned. Each cAb-expressing CHO cell line was weaned into serum-free medium, and the cAb was purified by protein A affinity chromatography. The levels of cAb production for the various CHO cell lines varied from 10 to 20 mg/liter. Purified anti-HCV cAbs were tested with Abbott HCV immunoassays and showed reactivity. Moreover, yeast surface display combined with alanine-scanning mutagenesis was used to map the epitope at the individual amino acid level. Our results suggest that these HCV cAbs are ideal controls, calibrators, and/or QC reagents for HCV assay standardization.
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Michaelsen, Terje E., Øistein Ihle, Karen Johanne Beckstrøm, Tove K. Herstad, Jan Kolberg, E. Arne Høiby, and Audun Aase. "Construction and Functional Activities of Chimeric Mouse-Human Immunoglobulin G and Immunoglobulin M Antibodies against the Neisseria meningitidis PorA P1.7 and P1.16 Epitopes." Infection and Immunity 71, no. 10 (October 2003): 5714–23. http://dx.doi.org/10.1128/iai.71.10.5714-5723.2003.

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ABSTRACT We studied the in vitro protective activities of human immunoglobulin G1 (IgG1), IgG3, and IgM antibodies against group B meningococci by constructing sets of chimeric mouse-human antibodies (chIgG1, chIgG3, and chIgM, respectively) with identical binding regions against the P1.7 and P1.16 epitopes on PorA. This was done by cloning the V genes of three mouse hybridoma antibodies and subsequently transfecting vectors containing the homologous heavy- and light-chain genes into NSO cells. Cell clones secreting intact human chIgG1, chIgG3, or chIgM antibodies originating from three parent mouse antibodies were isolated. The functional affinities appeared to be similar for all human isotypes and surprisingly also for the pentameric chIgM antibody. chIgG1 exhibited greater serum bactericidal activity (SBA) than chIgG3, while chIgG3 was more efficient in inducing a respiratory burst (RB) associated with opsonophagocytosis than chIgG1 was. On the other hand, chIgM exhibited SBA similar to that of chIgG1, but it exhibited much higher RB activity than chIgG3 and chIgG1 exhibited. The antibodies against the P1.16 epitope were more efficient in terms of SBA than the antibodies against the P1.7 epitope were; thus, 10- to 40-fold-lower concentrations of antibodies against P1.16 than of antibodies against P1.7 were needed to induce SBA. On the other hand, antibodies against these epitopes were equally effective in inducing RB. Our results revealed differences in the functional activities of human chIgG1, chIgG3, and chIgM antibodies against meningococci, which might influence their protective effects against meningococcal disease.
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Schlender, Jörg, Birgit Bossert, Ursula Buchholz, and Karl-Klaus Conzelmann. "Bovine Respiratory Syncytial Virus Nonstructural Proteins NS1 and NS2 Cooperatively Antagonize Alpha/Beta Interferon-Induced Antiviral Response." Journal of Virology 74, no. 18 (September 15, 2000): 8234–42. http://dx.doi.org/10.1128/jvi.74.18.8234-8242.2000.

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ABSTRACT The functions of bovine respiratory syncytial virus (BRSV) nonstructural proteins NS1 and NS2 were studied by generation and analysis of recombinant BRSV carrying single and double gene deletions. Whereas in MDBK cells the lack of either or both NS genes resulted in a 5,000- to 10,000-fold reduction of virus titers, in Vero cells a moderate (10-fold) reduction was observed. Interestingly, cell culture supernatants from infected MDBK cells were able to restrain the growth of NS deletion mutants in Vero cells, suggesting the involvement of NS proteins in escape from cytokine-mediated host cell responses. The responsible factors in MDBK supernatants were identified as type I interferons by neutralization of the inhibitory effect with antibodies blocking the alpha interferon (IFN-α) receptor. Treatment of cells with recombinant universal IFN-α A/D or IFN-β revealed severe inhibition of single and double deletion mutants, whereas growth of full-length BRSV was not greatly affected. Surprisingly, all NS deletion mutants were equally repressed, indicating an obligatory cooperation of NS1 and NS2 in antagonizing IFN-mediated antiviral mechanisms. To verify this finding, we generated recombinant rabies virus (rRV) expressing either NS1 or NS2 and determined their IFN sensitivity. In cells coinfected with NS1- and NS2-expressing rRVs, virus replication was resistant to doses of IFN which caused a 1,000-fold reduction of replication in cells infected with wild-type RV or with each of the NS-expressing rRVs alone. Thus, BRSV NS proteins have the potential to cooperatively protect an unrelated virus from IFN-α/β mediated antiviral responses. Interestingly, BRSV NS proteins provided a more pronounced resistance to IFN in the bovine cell line MDBK than in cell lines of other origins, suggesting adaptation to host-specific antiviral responses. The findings described have a major impact on the design of live recombinant BRSV and HRSV vaccines.
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Bossert, Birgit, Sabrina Marozin, and Karl-Klaus Conzelmann. "Nonstructural Proteins NS1 and NS2 of Bovine Respiratory Syncytial Virus Block Activation of Interferon Regulatory Factor 3." Journal of Virology 77, no. 16 (August 15, 2003): 8661–68. http://dx.doi.org/10.1128/jvi.77.16.8661-8668.2003.

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ABSTRACT We have previously shown that the nonstructural (NS) proteins NS1 and NS2 of bovine respiratory syncytial virus (BRSV) mediate resistance to the alpha/beta interferon (IFN)-mediated antiviral response. Here, we show that they, in addition, are able to prevent the induction of beta IFN (IFN-β) after virus infection or double-stranded RNA stimulation. In BRSV-infected MDBK cells upregulation of IFN-stimulated genes (ISGs) such as MxA did not occur, although IFN signaling via JAK/STAT was found intact. In contrast, infection with recombinant BRSVs lacking either or both NS genes resulted in efficient upregulation of ISGs. Biological IFN activity and IFN-β were detected only in supernatants of cells infected with the NS deletion mutants but not with wild-type (wt) BRSV. Subsequent analyses of IFN-β promoter activity showed that infection of cells with the double deletion mutant BRSV ΔNS1/2, but not with BRSV wt, resulted in a significant increase in IFN-β gene promoter activity. Induction of the IFN-β promoter depends on the activation of three distinct transcription factors, NF-κB, ATF-2/c-Jun, and IFN regulatory factor 3 (IRF-3). Whereas NF-κB and ATF-2/c-Jun activities were readily detectable and comparable in both wt BRSV- and BRSV ΔNS1/2-infected cells, phosphorylation and transcriptional activity of IRF-3, however, were observed only after BRSV ΔNS1/2 infection. NS protein-mediated inhibition of IRF-3 activation and IFN induction should have considerable impact on the pathogenesis and immunogenicity of BRSV.
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30

Patwardhan, PranavPramod, Annapurna Chandrashekhar Taware, and Pragati Aditya Sathe. "Steroid cell tumour- NOS of the ovary in a young female." Annals of Pathology and Laboratory Medicine 5, no. 2 (2018): C36–38. http://dx.doi.org/10.21276/apalm.1597.

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31

Noviyanti, Atiek Rostika, Claudia Agesti, Yusi Deawati, and Dani Gustaman Syarif. "A Compatibility in the Single Cell of the NiO/LSGM/LSCF." Jurnal Kimia Sains dan Aplikasi 23, no. 10 (October 27, 2020): 346–52. http://dx.doi.org/10.14710/jksa.23.10.346-352.

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The compatibility between anode, electrolyte, and cathode in a solid fuel cell determines its performance. Research on the compatibility between fuel cell components is challenging, especially for SOFCs that operate at high temperatures. Therefore, efforts to reduce the operating temperature to become intermediate temperature SOFC (IT-SOFC) are essential to facilitate compatibility between its components. La0.6Sr0.4Co0.2Fe0.8O3-δ (LSCF) has been recognized as one of the most promising cathode materials for (IT-SOFC) due to its high electronic conductivity and excellent electrical performance. While La0.8Sr0.2Ga0.8Mg0.2O3–δ (LSGM) has a high oxygen ion conductivity at low temperatures, its chemical stability is still not good. LSGM is known to have interface reactivity with other components such as NiO and LSCF in fuel cells. This study looked at the compatibility of NiO/LSGM/LSCF cells prepared by the solid chemical synthesis method. Compatibility evaluation is determined by the Thermal Expansion Coefficient (TEC) parameter using the dilatometric method, Area Specific Resistance (ASR), and TBF area morphology by Scanning Electron Microscope-Energy Dispersive Spectroscopy (SEM-EDS). While the conductivity of the cells is determined by Electrochemical Impedance Spectroscopy (EIS). NiO/LSGM/LSCF cells have good compatibility with a value of 78.05 kg-1.K.A.s3.µ2 at a temperature of 600°C. The ASR values of cells tend to decrease with increasing temperature and conductivity values at small TEC values. Based on these parameter values, delamination in NiO/LSGM/LSCF cells did not occur.
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32

Tay, Moon Y. F., Wuan Geok Saw, Yongqian Zhao, Kitti W. K. Chan, Daljit Singh, Yuwen Chong, Jade K. Forwood, et al. "The C-terminal 50 Amino Acid Residues of Dengue NS3 Protein Are Important for NS3-NS5 Interaction and Viral Replication." Journal of Biological Chemistry 290, no. 4 (December 8, 2014): 2379–94. http://dx.doi.org/10.1074/jbc.m114.607341.

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Palese, P., D. Greenspan, S. Nakada, and M. Krystal. "Nuclear localization of NS1 and NS2 proteins in influenza a virus infected cells : Identification of nuclear signal sequences." Virus Research 3 (September 1985): 40. http://dx.doi.org/10.1016/0168-1702(85)90331-4.

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34

Li, Lili, Hui Zhao, Ping Liu, Chunfeng Li, Natalie Quanquin, Xue Ji, Nina Sun, et al. "PARP12suppresses Zika virus infection through PARP-dependent degradation of NS1 and NS3 viral proteins." Science Signaling 11, no. 535 (June 19, 2018): eaas9332. http://dx.doi.org/10.1126/scisignal.aas9332.

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35

Westaway, E. G., J. M. Mackenzie, M. T. Kenney, M. K. Jones, and A. A. Khromykh. "Ultrastructure of Kunjin virus-infected cells: colocalization of NS1 and NS3 with double-stranded RNA, and of NS2B with NS3, in virus-induced membrane structures." Journal of virology 71, no. 9 (1997): 6650–61. http://dx.doi.org/10.1128/jvi.71.9.6650-6661.1997.

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MITRA, PRATIP, and ROBERT F. MILLER. "Mechanism underlying rebound excitation in retinal ganglion cells." Visual Neuroscience 24, no. 5 (September 2007): 709–31. http://dx.doi.org/10.1017/s0952523807070654.

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Retinal ganglion cells (RGCs) display the phenomenon of rebound excitation, which is observed as rebound sodium action potential firing initiated at the termination of a sustained hyperpolarization below the resting membrane potential (RMP). Rebound impulse firing, in contrast to corresponding firing elicited from rest, displayed a lower net voltage threshold, shorter latency and was invariably observed as a phasic burst-like doublet of spikes. The preceding hyperpolarization leads to the recruitment of a Tetrodotoxin-insensitive depolarizing voltage overshoot, termed as the net depolarizing overshoot (NDO). Based on pharmacological sensitivities, we provide evidence that the NDO is composed of two independent but interacting components, including (1) a regenerative low threshold calcium spike (LTCS) and (2) a non-regenerative overshoot (NRO). Using voltage and current clamp recordings, we demonstrate that amphibian RGCs possess the hyperpolarization activated mixed cation channels/current,Ih, and low voltage activated (LVA) calcium channels, which underlie the generation of the NRO and LTCS respectively. At the RMP, theIhchannels are closed and the LVA calcium channels are inactivated. A hyperpolarization of sufficient magnitude and duration activatesIhand removes the inactivation of the LVA calcium channels. On termination of the hyperpolarizing influence,Ihadds an immediate depolarizing influence that boosts the generation of the LTCS. The concerted action of both conductances results in a larger amplitude and shorter latency NDO than either mechanism could achieve on its own. The NDO boosts the generation of conventional sodium spikes which are triggered on its upstroke and crest, thus eliciting rebound excitation.
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Zhang, Hangjie, Wenling Xiao, Min Zhao, Yingze Zhao, Yongli Zhang, Dan Lu, Shuangshuang Lu, et al. "The CD8+ and CD4+ T Cell Immunogen Atlas of Zika Virus Reveals E, NS1 and NS4 Proteins as the Vaccine Targets." Viruses 14, no. 11 (October 25, 2022): 2332. http://dx.doi.org/10.3390/v14112332.

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Zika virus (ZIKV)-specific T cells are activated by different peptides derived from virus structural and nonstructural proteins, and contributed to the viral clearance or protective immunity. Herein, we have depicted the profile of CD8+ and CD4+ T cell immunogenicity of ZIKV proteins in C57BL/6 (H-2b) and BALB/c (H-2d) mice, and found that featured cellular immunity antigens were variant among different murine alleles. In H-2b mice, the proteins E, NS2, NS3 and NS5 are recognized as immunodominant antigens by CD8+ T cells, while NS4 is dominantly recognized by CD4+ T cells. In contrast, in H-2d mice, NS1 and NS4 are the dominant CD8+ T cell antigen and NS4 as the dominant CD4+ T cell antigen, respectively. Among the synthesized 364 overlapping polypeptides spanning the whole proteome of ZIKV, we mapped 91 and 39 polypeptides which can induce ZIKV-specific T cell responses in H-2b and H-2d mice, respectively. Through the identification of CD8+ T cell epitopes, we found that immunodominant regions E294-302 and NS42351-2360 are hotspots epitopes with a distinct immunodominance hierarchy present in H-2b and H-2d mice, respectively. Our data characterized an overall landscape of the immunogenic spectrum of the ZIKV polyprotein, and provide useful insight into the vaccine development.
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Kapoor, Mini, Luwen Zhang, Muralidhara Ramachandra, Jingo Kusukawa, Kurt E. Ebner, and R. Padmanabhan. "Association between NS3 and NS5 Proteins of Dengue Virus Type 2 in the Putative RNA Replicase Is Linked to Differential Phosphorylation of NS5." Journal of Biological Chemistry 270, no. 32 (August 11, 1995): 19100–19106. http://dx.doi.org/10.1074/jbc.270.32.19100.

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Welbourn, Sarah, Robin Green, Isabelle Gamache, Serge Dandache, Volker Lohmann, Ralf Bartenschlager, Karen Meerovitch, and Arnim Pause. "Hepatitis C Virus NS2/3 Processing Is Required for NS3 Stability and Viral RNA Replication." Journal of Biological Chemistry 280, no. 33 (June 24, 2005): 29604–11. http://dx.doi.org/10.1074/jbc.m505019200.

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40

Lo, Mindy S., Robert M. Brazas, and Michael J. Holtzman. "Respiratory Syncytial Virus Nonstructural Proteins NS1 and NS2 Mediate Inhibition of Stat2 Expression and Alpha/Beta Interferon Responsiveness." Journal of Virology 79, no. 14 (July 2005): 9315–19. http://dx.doi.org/10.1128/jvi.79.14.9315-9319.2005.

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ABSTRACT Respiratory syncytial virus (RSV) subverts the antiviral interferon (IFN) response, but the mechanism for this evasion was unclear. Here we show that RSV preferentially inhibits IFN-α/β signaling by expression of viral NS1 and NS2. Thus, RSV infection or expression of recombinant NS1 and NS2 in epithelial host cells causes a marked decrease in Stat2 levels and the consequent downstream IFN-α/β response. Similarly, NS1/NS2-deficient RSV no longer decreases Stat2 levels or IFN responsiveness. RSV infection decreased human but not mouse Stat2 levels, so this mechanism of IFN antagonism may contribute to viral host range, as well as immune subversion.
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Khromykh, Alexander A., Petra L. Sedlak, Kimberley J. Guyatt, Roy A. Hall, and Edwin G. Westaway. "Efficient trans-Complementation of the Flavivirus Kunjin NS5 Protein but Not of the NS1 Protein Requires Its Coexpression with Other Components of the Viral Replicase." Journal of Virology 73, no. 12 (December 1, 1999): 10272–80. http://dx.doi.org/10.1128/jvi.73.12.10272-10280.1999.

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ABSTRACT Successful trans-complementation of the defective Kunjin virus (KUN) RNA FLdGDD with a deletion of the RNA polymerase motif GDD in the NS5 gene by using a BHK cell line, repBHK, that continuously produced a functionally active KUN replication complex (RC) from replicon RNA was recently reported (A. A. Khromykh, M. T. Kenney, and E. G. Westaway, J. Virol. 72:7270–7279, 1998). In order to identify whether this complementation of FLdGDD RNA was provided by the wild-type NS5 protein alone or with the help of other nonstructural (NS) proteins also expressed in repBHK cells, we generated BHK cell lines stably producing the individual NS5 protein (SRns5BHK) or the NS1-NS5 polyprotein (SRns1-5BHK) by using a heterologous expression vector based on a modified noncytopathic Sindbis replicon. Western blot analysis with anti-NS5 antibodies showed that the level of production of NS5 was significantly higher in SRns5BHK cells than in SRns1-5BHK cells. Despite the higher level of expressed NS5,trans-complementation of FLdGDD RNA was much less efficient in SRns5BHK cells than in SRns1-5BHK cells and produced at least 100-fold less of the secreted complemented virus. In contrast, efficient complementation of KUN RNA with lethal cysteine-to-alanine mutations in the NS1 gene was achieved both in BHK cells producing the individual KUN NS1 protein from the Sindbis replicon vector and in repBHK cells, with both cell lines expressing similar amounts of NS1 protein. These results clearly demonstrate that flavivirus NS5 coexpressed with other components of the viral replicase possesses much higher functional (trans-complementing) activity than individually expressed NS5 and that efficienttrans-complementation of mutated flavivirus NS1 and NS5 proteins occurs by different mechanisms. The results are interpreted and discussed in relation to our proposed model of formation of the flavivirus RC largely based on previous ultrastructural and biochemical analyses of KUN replication.
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Liu, Wen Jun, Petra L. Sedlak, Natasha Kondratieva, and Alexander A. Khromykh. "Complementation Analysis of the Flavivirus Kunjin NS3 and NS5 Proteins Defines the Minimal Regions Essential for Formation of a Replication Complex and Shows a Requirement of NS3 in cis for Virus Assembly." Journal of Virology 76, no. 21 (November 1, 2002): 10766–75. http://dx.doi.org/10.1128/jvi.76.21.10766-10775.2002.

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ABSTRACT We have previously reported successful trans-complementation of defective Kunjin virus genomic RNAs with a range of large lethal deletions in the nonstructural genes NS1, NS3, and NS5 (A. A. Khromykh et al., J. Virol. 74:3253-3263, 2000). In this study we have mapped further the minimal region in the NS5 gene essential for efficient trans-complementation of genome-length RNAs in repBHK cells to the first 316 of the 905 codons. To allow amplification and easy detection of complemented defective RNAs with deletions apparently affecting virus assembly, we have developed a dual replicon complementation system. In this system defective replicon RNAs with a deletion(s) in the nonstructural genes also encoded the puromycin resistance gene (PAC gene) and the reporter gene for β-galactosidase (β-Gal). Complementation of these defective replicon RNAs in repBHK cells resulted in expression of PAC and β-Gal which allowed establishment of cell lines stably producing replicating defective RNAs by selection with puromycin and comparison of replication efficiencies of complemented defective RNAs by β-Gal assay. Using this system we demonstrated that deletions in the C-terminal 434 codons of NS3 (codons 178 to 611) were complemented for RNA replication, while any deletions in the first 178 codons were not. None of the genome-length RNAs containing deletions in NS3 shown to be complementable for RNA replication produced secreted defective viruses during complementation in repBHK cells. In contrast, structural proteins produced from these complemented defective RNAs were able to package helper replicon RNA. The results define minimal regions in the NS3 and NS5 genes essential for the formation of complementable replication complex and show a requirement of NS3 in cis for virus assembly.
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43

Vanzetto, A. B., A. Moehlecke, T. Crestani, J. V. Z. Britto, and I. Zanesco. "Revisão sistemática de células solares de silício base n: estruturas e eficiências." Cerâmica 68, no. 388 (December 2022): 450–68. http://dx.doi.org/10.1590/0366-69132022683883369.

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Resumo Células solares com emissor e face posterior passivada (PERC, passivated emitter and rear cell) vêm dominando o mercado fotovoltaico em razão de seu processo de fabricação ser compatível com as linhas industriais que vinham sendo utilizadas e pela produção de dispositivos de alta eficiência. Atualmente o silício tipo p é o mais utilizado pela indústria de células solares, mas o silício tipo n deve ganhar mercado nos próximos anos juntamente com o emprego de lâminas de espessura reduzida. O objetivo deste trabalho é apresentar uma revisão sistemática dos principais estudos na área de células solares base n, sendo elas do tipo PERC, PERT (passivated emitter-rear totally diffused) e TOPCon (tunnel oxide passivated contact), com ênfase para a abordagem de contatos seletivos, emissores seletivos e nos processos utilizados, bem como na análise de células solares de espessura reduzida em relação ao padrão da indústria atual.
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44

Edward, Zulkarnain, and Tsutomu Takegami. "Localization and Functions of Japanese Encephalitis Virus Nonstructural Proteins NS3 and NS5 for Viral RNA Synthesis in the Infected Cells." Microbiology and Immunology 37, no. 3 (March 1993): 239–43. http://dx.doi.org/10.1111/j.1348-0421.1993.tb03206.x.

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45

Seress, László, Hajnalka Ábrahám, András Hajnal, Hong Lin, and Susan Totterdell. "NOS-positive local circuit neurons are exclusively axo-dendritic cells both in the neo- and archicortex of the rat brain." Brain Research 1056, no. 2 (September 2005): 183–90. http://dx.doi.org/10.1016/j.brainres.2005.07.034.

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46

Yi, MinKyung, Yinghong Ma, Jeremy Yates, and Stanley M. Lemon. "Compensatory Mutations in E1, p7, NS2, and NS3 Enhance Yields of Cell Culture-Infectious Intergenotypic Chimeric Hepatitis C Virus." Journal of Virology 81, no. 2 (November 1, 2006): 629–38. http://dx.doi.org/10.1128/jvi.01890-06.

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ABSTRACT There is little understanding of mechanisms underlying the assembly and release of infectious hepatitis C virus (HCV) from cultured cells. Cells transfected with synthetic genomic RNA from a unique genotype 2a virus (JFH1) produce high titers of virus, while virus yields are much lower with a prototype genotype 1a RNA containing multiple cell culture-adaptive mutations (H77S). To characterize the basis for this difference in infectious particle production, we constructed chimeric genomes encoding the structural proteins of H77S within the background of JFH1. RNAs encoding polyproteins fused at the NS2/NS3 junction (“H-NS2/NS3-J”) and at a site of natural, intergenotypic recombination within NS2 [“H-(NS2)-J”] produced infectious virus. In contrast, no virus was produced by a chimera fused at the p7-NS2 junction. Chimera H-NS2/NS3-J virus (vH-NS2/NS3-J) recovered from transfected cultures contained compensatory mutations in E1 and NS3 that were essential for the production of infectious virus, while yields of infectious vH-(NS2)-J were enhanced by mutations within p7 and NS2. These compensatory mutations were chimera specific and did not enhance viral RNA replication or polyprotein processing; thus, they likely compensate for incompatibilities between proteins of different genotypes at sites of interactions essential for virus assembly and/or release. Mutations in p7 and NS2 acted additively and increased the specific infectivity of vH-(NS2)-J particles, while having less impact on the numbers of particles released. We conclude that interactions between NS2 and E1 and p7 as well as between NS2 and NS3 are essential for virus assembly and/or release and that each of these viral proteins plays an important role in this process.
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Bukovsky, A. "Ovarian Stem Cells and Mammalian Neo-Oogenesis." Microscopy and Microanalysis 14, S2 (August 2008): 1474–75. http://dx.doi.org/10.1017/s1431927608085000.

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48

van Dijk, M. C. M., and T. J. C. van Berkel. "Targeting of neo-chylomicrons to liver cells." European Journal of Pharmacology 183, no. 2 (July 1990): 378–79. http://dx.doi.org/10.1016/0014-2999(90)93254-n.

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49

Karsthof, R., P. Räcke, H. von Wenckstern, and M. Grundmann. "Semi-transparent NiO/ZnO UV photovoltaic cells." physica status solidi (a) 213, no. 1 (October 22, 2015): 30–37. http://dx.doi.org/10.1002/pssa.201532625.

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Xue, Zhichao, Xingyuan Liu, Nan Zhang, Hong Chen, Xuanming Zheng, Haiyu Wang, and Xiaoyang Guo. "High-Performance NiO/Ag/NiO Transparent Electrodes for Flexible Organic Photovoltaic Cells." ACS Applied Materials & Interfaces 6, no. 18 (August 29, 2014): 16403–8. http://dx.doi.org/10.1021/am504806k.

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