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Infection with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) stimulates the plasma B cells to secrete specific antibodies against the viral antigen. However, not all antibodies can prevent the virus from entering the cells. The subpopulation of antibodies which blocks the entry of the virus into host cells is termed neutralizing antibodies (NAbs). The gold standard test for the detection of NAbs is the viral plaque reduction and neutralization test; however, various other methods can also be utilized to detect NAbs. In this study, we have developed an Enzyme Linked Immunosobent Assay (ELISA)-based protocol for rapid detection of SARS CoV-2 NAb by inhibiting the binding of the spike protein receptor-binding domain to angiotensin converting enzyme 2 and compared it with cPASS neutralizing antibody kit, which was approved by the Food and Drug Administration (FDA). The results obtained suggest that the in-house ELISA developed for the detection of NAbs against SARS-CoV-2 is rapid and reliable. Compared to FDA-approved GenScript's cPass assay, the specificity and the sensitivity of the in-house-developed ELISA kit were 100% (95% confidence intervals of 69.15-100.00) and 96% (95% confidence intervals of 86.29-99.51), respectively. Thus, the ELISA protocol developed to test the neutralizing activities of antibodies is rapid, which requires a BSL-2 infrastructure facility and can be easily performed. It has very high potential applications in the rapid screening of NAb against SARS-CoV-2.
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COVID-19 , SARS-CoV-2 , Humanos , COVID-19/diagnóstico , Anticorpos Antivirais , Anticorpos Neutralizantes , Ensaio de Imunoadsorção Enzimática , Glicoproteína da Espícula de Coronavírus/químicaRESUMO
Platelets or thrombocytes play an important role in thrombosis and maintaining hemostasis. Thrombocytes help in forming blood clots at the site of the wound. When the level of platelets decreases, uncontrolled bleeding occurs which can result in mortality. A decrease in the blood platelet level is known as thrombocytopenia which can be caused due to various reasons. A variety of treatment options are available for thrombocytopenia like platelet transfusion, splenectomy, platelet management with various types of corticosteroids, and recombinant interleukin-11 (rhIL-11). The use of rhIL-11 is approved by FDA for the treatment of thrombocytopenia. rhIL-11 is a recombinant cytokine that is administered to patients suffering from chemotherapy-induced thrombocytopenia as it enhances megakaryocytic proliferation which aids in platelet production. But this treatment has various side effects and is costly. Hence, there is a crucial need to identify cost-effective alternative strategies that present no side effects. The majority of the population in low-income countries requires a functional and cost-effective treatment for low thrombocyte count. Carica papaya is a tropical herbaceous plant that has been reported in recovering low platelet count during dengue virus infection. Even though multiple benefits of the Carica papaya leaf extract (CPLE) are popular, the active compound present in it, which mediates these benefits, remains to be identified. This review aims to highlight the different aspects of rhIL-11 and CPLE-induced platelet counts and their limitations and benefits in the treatment of thrombocytopenia. The literature related to the treatment of thrombocytopenia using rhIL-11 and CPLE from 1970 to 2022 was searched using PubMed and Google Scholar databases with the keywords Recombinant Interleukin-11, Papaya Leaf Extract, Thrombocytopenia, and Platelets.
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When sojourners visit to high altitude, various symptoms may appear in the body including gastrointestinal symptoms such as poor appetite or nausea, vomiting, and incapacitating. The gastrointestinal tract is a key organ involved in the development of acute mountain sickness (AMS). The intestinal epithelial lining is covered by mucus layer. Mucosal barrier is considered as first line of protection of the gut wall which not only helps in lubricating and facilitating progression of bolus but also protects intestinal epithelial lining. Gut microbes play a major role in alterations of mucus barrier and may have important role in curtailing gastrointestinal symptoms at high altitude. In our previous study, we have reported ~ 17% decrease in Akkermansia muciniphila bacteria under hypobaric hypoxia exposure in Sprague-Dawley rats. A. muciniphila is a mucin-degrading bacterium. Its presence in the human intestine is inversely associated to a number of diseases. A. muciniphila is found in the mucus layer, where it helps to maintain intestinal integrity and protects from various inflammatory diseases. Hypoxia decreases A. muciniphila bacterium in gut leading to gastrointestinal barrier injury. It could be an important probiotic that may have physiological benefits in high-altitude hypoxia induced clinical scenarios. A large-scale clinical experiments, production feasibility, and regulatory clearances need to be resolved to develop it as next generation probiotic. In this review, we have searched various databases including PubMed and Google Scholar with keywords Akkermansia muciniphila, A. muciniphila, human physiology, etc. to comprehensively highlight the importance of this gut bacterium. KEY POINTS: ⢠High-altitude hypoxia leads to gastrointestinal barrier injury. ⢠Hypoxia decreases Akkermansia muciniphila bacterium in gut. ⢠A. muciniphila as probiotic may help to maintain intestinal integrity.
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Doença da Altitude , Gastroenteropatias , Animais , Ratos , Humanos , Ratos Sprague-Dawley , Verrucomicrobia , HipóxiaRESUMO
Coronavirus disease 2019 (COVID-19) continuously affecting the lives of millions of people. The virus is spread through the respiratory route to an uninfected person, causing mild-to-moderate respiratory disease-like symptoms that sometimes progress to severe form and can be fatal. When the host is infected with the virus, both innate and adaptive immunity comes into play. The effector T cells act as the master player of adaptive immune response in eradicating the virus from the system. But during cancer and chronic viral infections, the fate of an effector T cell is altered, and the T cell may enters a state of exhaustion, which is marked by loss of effector function, depleted proliferative capacity and cytotoxic effect accomplished by an increased expression of numerous inhibitory receptors such as programmed cell death protein 1 (PD-1), lymphocyte-activation protein 3 (LAG-3), and cytotoxic T lymphocyte-associated antigen 4 (CTLA-4) on their surface. Various other transcriptional and epigenetic changes take place inside the T cell when it enters into an exhausted state. Latest studies point toward the induction of an abnormal immune response such as lymphopenia, cytokine storm, and T cell exhaustion during SARS-CoV-2 (severe acute respiratory syndrome coronavirus 2) infection. This review sheds light on the dysfunctional state of T cells during chronic viral infection and COVID-19. Understanding the cause and the effect of T cell exhaustion observed during COVID-19 may help resolve new therapeutic potentials for treating chronic infections and other diseases.
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COVID-19 , Imunidade Adaptativa , Síndrome da Liberação de Citocina , Humanos , SARS-CoV-2 , Linfócitos TRESUMO
Over the last twenty months, the attention of the world has been focusing on managing the unprecedented and devastating wave of COVID-19 caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV 2) and mitigating its impacts. Recent findings indicated that high levels of pro-inflammatory cytokines are leading cause of poor prognosis in severely ill COVID-19 patients. Presently, the multiple variants and highly contagious nature of virus makes challenge humongous. The shortage and vaccine hesitancy also prompted to develop antiviral therapeutic agents to manage this pandemic. Nanocurcumin has potential antiviral activities and also beneficial in post COVID inflammatory complications. We have developed nanocurcumin based formulation using pyrroloquinoline quinone (PQQ) which protects cardio-pulmonary function and mitochondrial homeostasis in hypobaric hypoxia induced right ventricular hypertrophy in animal model and human ventricular cardiomyocytes. Nanocurcumin based formulation (NCF) with improved bioavailability, has proven several holistic therapeutic effects including myocardial protection, and prevents edema formation, anti-inflammatory and antioxidant properties, maintaining metabolic and mitochondrial homeostasis under hypoxic condition. The post COVID-inflammatory syndrome also reported to cause impaired heart function, lung injuries and increased C-reactive protein level in severely ill patients. Thus, we speculate that NCF could be a new treatment option to manage post COVID-19 inflammatory syndrome.
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Tratamento Farmacológico da COVID-19 , Animais , Antioxidantes/farmacologia , Humanos , Hipóxia/tratamento farmacológico , Hipóxia/metabolismo , Mitocôndrias , PandemiasRESUMO
AIM: Andrographolide, the major bioactive compound of the plant Andrographis paniculata, exerts anti-inflammatory, cyto-, neuro- and hepato-protective effects. Traditional remedies for infectious diseases include A. paniculata for maladies like fever, pain, rashes which are associated with chikungunya and other arboviral diseases. Since andrographolide and A. paniculata have potent antiviral properties, the present review aims to provide a comprehensive report of symptoms and immunological molecules involved in chikungunya virus (CHIKV) infection and the therapeutic role of andrographolide in the mitigation of chikungunya and associated symptoms. MATERIALS AND METHODS: Studies on the therapeutic role of A. paniculata and andrographolide in chikungunya and other viral infections published between 1991 and 2021 were searched on various databases. RESULTS AND DISCUSSION: The havoc created by chikungunya is due to the associated debilitating symptoms including arthralgia and myalgia which sometimes remains for years. The authors reviewed and summarized the various symptoms and immunological molecules related to CHIKV replication and associated inflammation, oxidative and unfolded protein stress, apoptosis and arthritis. Additionally, the authors suggested andrographolide as a remedy for chikungunya and other arboviral infections by highlighting its role in the regulation of molecules involved in unfolded protein response pathway, immunomodulation, inflammation, virus multiplication, oxidative stress, apoptosis and arthritis. CONCLUSION: The present review demonstrated the major complications associated with chikungunya and the role of andrographolide in alleviating the chikungunya associated symptoms to encourage further investigations using this promising compound towards early development of an anti-CHIKV drug. Chemical Compound studied: andrographolide (PubChem CID: 5318517).
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Antivirais/farmacologia , Artrite Infecciosa/tratamento farmacológico , Febre de Chikungunya/tratamento farmacológico , Diterpenos/farmacologia , Animais , Antivirais/uso terapêutico , Artrite Infecciosa/virologia , Febre de Chikungunya/transmissão , Febre de Chikungunya/virologia , Vírus Chikungunya/efeitos dos fármacos , Diterpenos/uso terapêutico , Interações entre Hospedeiro e Microrganismos , HumanosRESUMO
Innate immune memory, a crucial mechanism of epigenetically mediated myeloid cell plasticity, alters subsequent immune responses majorly by two types of immunological imprinting, training, and tolerance. Recent pioneer studies provided proof-of-principle for generation of both types of innate immune memory in brain macrophage, microglial cells. This novel study was designed to investigate whether the pattern of immune response generation, induced by peripheral administration of recombinant alarmin HMGB1, alone and in combination with other recombinant cytokines, is affected by prior exposure. The experimental outcomes revealed that full length recombinant HMGB1 exposure for seven consecutive days exhibit inflammatory response as evidenced by enhanced expression of inflammatory biomarkers and neurodegeneration. In contrary, combined doses of HMGB1 and IL-1ß, for three and seven consecutive days, exhibited lower inflammatory state compared to its alone HMGB1 counterpart. The immune tolerance state was evident by microglial polarization towards non-reactive M2 state, lower astrocyte activation, epigenetic reprogramming, and decreased neurodegeneration. This is the first demonstration that HMGB1 and IL-1ß priming can differentially affect inflammation in the brain when a host is confronted with a second, third stimulus or so on. The findings were further validated by suppressing major regulators of epigenetic reprogramming, by intranasal delivery of specific siRNAs targeting those regulators. These results may provide new evidence for the involvement of recombinant endogenous cytokine induced generation of innate immune tolerance within microglial cells and indicated the possible potential role in mediating cognitive and behavioural alterations during inflammatory diseases.
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Encéfalo/imunologia , Proteína HMGB1/imunologia , Imunidade Inata/imunologia , Interleucina-1beta/imunologia , Microglia/imunologia , Animais , Tolerância Imunológica/imunologia , Masculino , Camundongos , Camundongos Endogâmicos BALB CRESUMO
Natural product based medicines are being used in India since 12th century BC and their efficacies are well established in Indian traditional medicine system. However, the mechanism of action as per the modern medicinal system was not well reported. Plant-derived natural compounds are very useful for inflammatory disorders and other diseases such as cancer. Various medicines like artemisinin, vincristine, vinblastine, taxol, and so forth, are invaluable contributions of nature to modern medicine. The role of transcription factor NF-κB was well delineated in inflammatory processes. Binding of NF-κB to the promoter site of several inflammatory genes activate them to secrete proinflammatory cytokines and chemokines. Plant derived natural compounds like andrographolide could be useful in inflammatory disorders as it directly inhibit the binding of NF-κB with DNA at promoter site. Transcription factor NF-κB is a master regulator of the proinflammatory gene expression program and since it was suppressed by andrographolide, hence andrographolide is rightly termed as regulator of master regulator.
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ETHNOPHARMACOLOGICAL RELEVANCE: Traditional plant-derived medicines have enabled the mankind in curing the wide spectrum of diseases throughout the ages. Andrographis paniculata (Burm.f.) Nees, is one of the traditional plant used as a folk medicine for the management of inflammation, arthritis, viral-bacterial infections and other ailments in India, China, Malaysia and other South-East Asian countries. Its major bioactive compound; andrographolide, a diterpenoid, also exerts cytoprotective properties and is reported to be effective in neuroprotection, hepatoprotection, etc. AIM: The study is aimed to explore the role of andrographolide in treatment of complete freund's adjuvant (CFA) induced arthritis. MATERIALS AND METHODS: The influx of immune cells, release of pro-inflammatory cytokines and subsequent accumulation of synovial fluid (swelling) and pain manifest into the disease. The present study used CFA induced Balb/c mice model and treated them intraperitoneally with andrographolide and dexamethasone (used as a positive control) on alternate days for six days. After 6 days, blood and peritoneal macrophages were collected to evaluate the expression of various arthritic markers and paw edema was measured on all days. RESULTS: The in vitro and ex vivo experiments showed that andrographolide treated animal group had reduced paw edema, cell cytotoxicity and nitric oxide production than dexamethasone treated animal group. Further, the study revealed the mechanistic role of andrographolide in treatment of arthritis by suppressing battery of molecules like COX-2, NF-κB, p-p38, CD40, TNF-α, IL-1ß and IL-6 involved in arthritis. CONCLUSION: The study showed the potent anti-arthritic effects of andrographolide and warrants further investigations on andrographolide for the development of safe and effective anti-arthritic drug.
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Anti-Inflamatórios/farmacologia , Antirreumáticos/farmacologia , Citocinas/antagonistas & inibidores , Diterpenos/farmacologia , Mediadores da Inflamação/antagonistas & inibidores , Articulações/efeitos dos fármacos , Macrófagos Peritoneais/efeitos dos fármacos , Animais , Artrite Experimental/induzido quimicamente , Artrite Experimental/imunologia , Artrite Experimental/metabolismo , Células Cultivadas , Citocinas/metabolismo , Feminino , Adjuvante de Freund , Mediadores da Inflamação/metabolismo , Articulações/imunologia , Articulações/metabolismo , Macrófagos Peritoneais/imunologia , Macrófagos Peritoneais/metabolismo , Masculino , Camundongos Endogâmicos BALB C , Transdução de SinaisRESUMO
High mobility group box 1 (HMGB1) is an endogenous alarmin that drives the pathogenesis of neurodegenerative disorders including cognitive decline. Therefore, HMGB1 is thought to be a common biomarker as well as promising therapeutic target for neuroinflammation associated with neurocognitive disorders. Here, for the first time, we have unmasked the potential inhibitory effect of a novel receptor of HMGB1-CXCL12 complex; atypical chemokine receptor 3 (ACKR3/CXCR7) on HMGB1 induced glial phenotype switching, neuroinflammation, and subsequent memory loss. Upregulation of CXCR7 inhibits HMGB1-CXCL12 complex induced peripheral immune cells infiltration to CNS by regulating blood-brain barrier (BBB) integrity in HMGB1 induced dementia model of mice. Whereas, gene knockdown study by RNA interference (non-invasive intranasal delivery to animal model) shows CXCR7 ablation aggravates inflammatory responses in hippocampus region and immune cell infiltration to CNS tissue by breached BBB. This study also indicates the important role of CXCR7 molecule in maintaining CNS homeostasis by balancing M1/M2 microglia, A1/A2 astrocytes, long term potentiation/long term depression markers which ultimately ameliorates HMGB1 induced neurodegeneration, synaptic depression and memory loss (assessed by both radial arm maze and Morris water maze) in male mice model of dementia. Overall, the study summarizes several significant protective functions afforded by CXCR7 against HMGB1 induced disbalance in neuroimmunological axis, neurodegeneration and memory loss and thereby provides a new paradigm for strategic development of novel therapeutics against neurodegenerative diseases with dementia as a common symptom.
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Alarminas/farmacologia , Transtornos da Memória/metabolismo , Receptores CXCR/metabolismo , Animais , Astrócitos/efeitos dos fármacos , Astrócitos/metabolismo , Astrócitos/patologia , Barreira Hematoencefálica/efeitos dos fármacos , Barreira Hematoencefálica/metabolismo , Barreira Hematoencefálica/patologia , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Encéfalo/patologia , Quimiocina CXCL12/metabolismo , Disfunção Cognitiva/induzido quimicamente , Disfunção Cognitiva/metabolismo , Disfunção Cognitiva/patologia , Feminino , Masculino , Transtornos da Memória/induzido quimicamente , Transtornos da Memória/patologia , Camundongos , Microglia/efeitos dos fármacos , Microglia/metabolismo , Microglia/patologia , Neuroglia/metabolismo , Neuroimunomodulação/fisiologia , Neuroproteção , Receptores CXCR/agonistas , Receptores CXCR4/metabolismo , Proteínas Recombinantes/farmacologia , Transdução de SinaisRESUMO
Traditional antibiotic susceptibility testing methods take several days to confirm and start disease treatment. The lack of new antibiotics or drugs warrants a need for optimization of current diagnostic tools for immediate antibiotic susceptibility testing. We present a rapid screening method to evaluate the response of bacteria to antibiotics based upon the electrochemical measurement of live bacterial cell metabolic activity using an electroactive redox dye, resazurin. A thin film of Pt deposited over a glass substrate using the direct current sputtering technique was used as a working bio-electrode for electrochemical readouts. X-ray diffraction and scanning electron microscopy was carried out to characterize the Pt thin film. We tested the efficacy of the method using two different strains, Klebsiella pneumoniae (ATCC-700603) and Escherichia coli (ATCC-25922), against ampicillin, kanamycin and tetracycline. The dye, on incubation with viable bacteria, undergoes reduction and lowers the corresponding peak current value. However, in the presence of an effective antibacterial agent, reduction did not occur due to bacterial cell death and absence of a reducing environment. The electrochemical changes in peak current values were monitored using the differential pulse voltammetry technique and interpretation of the results obtained was based upon changes in peak current values. Our results depict a new methodology where a concentration of 104 cells/mL cells can be detected in less than 4â¯h. The results were also compared with the conventional disc diffusion method for susceptibility testing which has a bacterial incubation time of 18-24â¯h. The method can potentially be used for monitoring the susceptibility of bacterial strains towards existing antibacterial agents in an easy, rapid, reliable and inexpensive manner without any pre-cultivation of bacteria.
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Ampicilina/farmacologia , Antibacterianos/farmacologia , Escherichia coli/efeitos dos fármacos , Canamicina/farmacologia , Klebsiella pneumoniae/efeitos dos fármacos , Oxazinas/química , Tetraciclina/farmacologia , Xantenos/química , Eletrodos , Testes de Sensibilidade Microbiana/métodos , Platina/químicaRESUMO
Brain, being the highest consumer of oxygen, is prone to increased risk of hypoxia-induced neurological insults. In response to hypoxia, microglia, the major resident immune cells of brain switches to an activated phenotype and promote inflammatory responses leading to tissue damage and loss of cognitive functions including working memory impairment. Till date, no proven clinical therapeutics is available to retard the progression of neurodegenerative memory impairment. In the present study, we investigated the therapeutic potential of intranasal small interfering RNA (siRNA) delivery in a mouse model of hypoxia-induced working memory impairment using microglial receptor, Mac-1 as a target gene. Here, we implicate Mac-1 scavenger receptor in microglial phenotype switching, neurodegeneration in prefrontal cortex, hippocampus and working memory impairment. RNA mediated silencing of Mac-1 in both in vitro and in vivo model showed significant impact of it on hypoxia induced altered expression of Mac-1 endogenous ligand, signaling cascade proteins, transcription factors and NADPH oxidase pathway. Efficient degradation of Mac-1 mRNA suppressed expression of M1 phenotypic markers, inflammatory chemokines, and cytokines, but on the other hand, it upregulated M2 phenotypic markers and anti-inflammatory cytokines. Neuronal viability and synaptic plasticity markers were also modulated significantly by this strategy. Behavioral study revealed significant downregulation in the number of working memory errors at a time-dependent manner after silencing the Mac-1 gene during continuous hypoxic exposure. The novel findings of this study for the very first time, unmasked the role of Mac-1 receptor in neurodegenerative disease progression under hypoxic condition and at the same time indicated the potential therapeutic value of this non-invasive siRNA delivery approach for treating working memory loss.
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Hipóxia/tratamento farmacológico , Antígeno de Macrófago 1 , Transtornos da Memória/tratamento farmacológico , Microglia/efeitos dos fármacos , Nootrópicos/administração & dosagem , RNA Interferente Pequeno/administração & dosagem , Administração Intranasal , Animais , Encéfalo/efeitos dos fármacos , Encéfalo/metabolismo , Células Cultivadas , Citocinas/metabolismo , Modelos Animais de Doenças , Hipóxia/metabolismo , Hipóxia/psicologia , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/psicologia , Antígeno de Macrófago 1/genética , Antígeno de Macrófago 1/metabolismo , Masculino , Transtornos da Memória/etiologia , Transtornos da Memória/metabolismo , Memória de Curto Prazo/efeitos dos fármacos , Memória de Curto Prazo/fisiologia , Camundongos , Microglia/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , RNA Mensageiro/metabolismo , Distribuição AleatóriaRESUMO
CONTEXT: Hippophae rhamnoides L. (Elaeagnaceae), commonly known as seabuckthorn (SBT), is known for its medicinal and nutritional properties. OBJECTIVE: Evaluation of in vivo adjuvant activity of SBT leaf extract (SBTE) with inactivated rabies virus antigen (Rb). MATERIALS AND METHODS: Swiss albino mice were immunized with aqueous-alcoholic SBTE (100 mg/kg body weight) or algel (aluminium hydroxide gel) with or without Rb (5% v/v). After priming, booster was administered on day 14. Rabies virus neutralizing antibody (RVNA) titers were estimated by rapid fluorescent focus inhibition test in sera samples collected on days 7, 14, 21, 28 and 35. Effect of adjuvant administration on cytotoxic T lymphocytes (CTLs), memory T cells, plasma and CD11c+ cells was studied by flow cytometry. In vitro hemolysis was assayed in human RBC. RESULTS: RVNA titers were significantly enhanced (p < 0.05) after booster administration in mice immunized with SBTE + Rb as compared to the controls. In combination, SBTE, algel and Rb, enhanced the RVNA titers. CTLs significantly increased (p < 0.05) in SBTE + Rb immunized mice. Memory T cells and plasma cells were 27.9 and 15.9%, respectively, in SBTE + Rb immunized mice as compared to that of 20.3 and 11.3%, respectively, in Rb immunized group. SBTE + Rb enhanced peritoneal CD11c+ cells (25.8%) as compared to 9.4% cells in Rb immunized mice, showed 3.2-fold increment in LPS induced IL-1ß. No RBC hemolysis was observed with SBTE. CONCLUSIONS: This study demonstrates the potential adjuvant activity of SBTE with Rb by increasing RVNA titers and CTL response.
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Antígenos Virais/administração & dosagem , Etanol/administração & dosagem , Hippophae , Extratos Vegetais/administração & dosagem , Folhas de Planta , Vírus da Raiva/efeitos dos fármacos , Animais , Quimioterapia Adjuvante , Feminino , Humanos , Masculino , Camundongos , Extratos Vegetais/isolamento & purificação , Vírus da Raiva/fisiologia , Linfócitos T/efeitos dos fármacos , Linfócitos T/fisiologiaRESUMO
High-altitude sojourn above 8000 ft is increasing day by day either for pilgrimage, mountaineering, holidaying or for strategic reasons. In India, soldiers are deployed to these high mountains for their duty or pilgrims visit to the holy places, which are located at very high altitude. A large population also resides permanently in high altitude regions. Every year thousands of pilgrims visit Holy cave of Shri Amarnath ji, which is above 15 000 ft. The poor acclimatization to high altitude may cause alteration in immunity. The low oxygen partial pressure may cause alterations in gut microbiota, which may cause changes in gut immunity. Effect of high altitude on gut-associated mucosal system is new area of research. Many studies have been carried out to understand the physiology and immunology behind the high-altitude-induced gut problems. Few interventions have also been discovered to circumvent the problems caused due to high-altitude conditions. In this review, we have discussed the effects of high-altitude-induced changes in gut immunity particularly peyer's patches, NK cells and inflammatory cytokines, secretary immunoglobulins and gut microbiota. The published articles from PubMed and Google scholar from year 1975 to 2017 on high-altitude hypoxia and gut immunity are cited in this review.
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Altitude , Microbioma Gastrointestinal/imunologia , Trato Gastrointestinal/imunologia , Hipóxia/imunologia , Imunidade nas Mucosas , Células Matadoras Naturais/imunologia , Nódulos Linfáticos Agregados/imunologia , Aclimatação , Formação de Anticorpos , Citocinas/metabolismo , Trato Gastrointestinal/microbiologia , Humanos , Imunoglobulina A/metabolismo , MontanhismoRESUMO
Over activation of glial cell derived innate immune factors induces neuro-inflammation that results in neurodegenerative disease, like working memory impairment. In this study, we have investigated the role of andrographolide, a major constituent of Andrographis paniculata plant, in reduction of reactive glial cell derived working memory impairment. Real time PCR, Western bloting, flow cytometric and immunofluorescence studies demonstrated that andrographolide inhibited lipopolysaccharide (LPS)-induced overexpression of HMGB1, TLR4, NFκB, COX-2, iNOS, and release of inflammatory mediators in primary mix glial culture, adult mice prefrontal cortex and hippocampus region. Active microglial and reactive astrocytic makers were also downregulated after andrographolide treatment. Andrographolide suppressed overexpression of microglial MIP-1α, P2X7 receptor and its downstream signaling mediators including-inflammasome NLRP3, caspase1 and mature IL-1ß. Furthermore, in vivo maze studies suggested that andrographolide treatment reversed LPS-induced behavioural and working memory disturbances including regulation of expression of protein markers like PKC, p-CREB, amyloid beta, APP, p-tau, synapsin and PSD-95. Andrographolide, by lowering expression of pro apoptotic genes and enhancing the expression of anti-apoptotic gene showed its anti-apoptotic nature that in turn reduces neurodegeneration. Morphology studies using Nissl and FJB staining also showed the neuroprotective effect of andrographolide in the prefrontal cortex region. The above studies indicated that andrographolide prevented neuroinflammation-associated neurodegeneration and improved synaptic plasticity markers in cortical as well as hippocampal region which suggests that andrographolide could be a novel pharmacological countermeasure for the treatment of neuroinflammation and neurological disorders related to memory impairment.
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Anti-Inflamatórios/farmacologia , Diterpenos/farmacologia , Transtornos da Memória/tratamento farmacológico , Memória de Curto Prazo/efeitos dos fármacos , Animais , Animais Recém-Nascidos , Ciclo-Oxigenase 2/metabolismo , Citocinas/metabolismo , Proteína Glial Fibrilar Ácida/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Mediadores da Inflamação/metabolismo , Masculino , Aprendizagem em Labirinto/efeitos dos fármacos , Transtornos da Memória/induzido quimicamente , Camundongos , Camundongos Endogâmicos BALB C , Óxido Nítrico Sintase Tipo II/metabolismo , Polissacarídeos/toxicidade , Córtex Pré-Frontal/efeitos dos fármacos , Córtex Pré-Frontal/metabolismo , Ratos , Receptor 4 Toll-Like/metabolismoRESUMO
Hippophae rhamnoides L. commonly known as Seabuckthorn (SBT), a wild shrub of family Elaegnacea, has extensively used for treating various ailments like skin diseases, jaundice, asthma, lung troubles. SBT leaves have been reported to possess several pharmacological properties including immunomodulatory, antioxidant, anti-inflammatory, antimicrobial and tissue regeneration etc. The present study was undertaken to evaluate the adjuvant property of supercritical carbon dioxide extracts (SCEs 300ET and 350ET) of SBT leaves in balb/c mice immunized with Tetanus and Diphtheria toxoids. The dynamic changes in the immune response were measured in terms of humoral and cell-mediated immune responses. We have seen the effect of SCEs on immunoglobulin subtypes and secondary immune response generation. In addition, the effect of SCEs on antigen specific cellular immunity was evaluated. Our results show that SCEs 300ET and 350ET significantly enhanced antibody titers in response to both TT and DT antigens. The secondary immune response generated was significantly increased in case of TT immunized animals. SCEs also enhanced cytokine levels (IFN-γ, IL-4, TNF-α and IL-1ß) and increased lymphoproliferation. Besides, both SCEs did not show any toxic effects. Therefore, the study suggests that SCEs are safe and have potent immunostimulatory activity and hence, seems to be a promising balanced Th1 and Th2 directing immunological adjuvant for various veterinary as well as human vaccines.
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Adjuvantes Imunológicos/administração & dosagem , Toxoide Diftérico/imunologia , Difteria/imunologia , Hippophae/imunologia , Extratos Vegetais/administração & dosagem , Toxoide Tetânico/imunologia , Tétano/imunologia , Animais , Citocinas/imunologia , Difteria/prevenção & controle , Feminino , Humanos , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral , Imunização Secundária , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Folhas de Planta , Tétano/prevenção & controleRESUMO
Rhodiola is native to the high altitude regions of Asia, Europe and Northern Hemisphere. It has a long history of use as a medicinal plant in various ailments, boosting immunity, increasing energy and mental capacity. It is also known as "Adaptogen" to help the body to adapt and resist stress. The part of the plant, which is used for medicinal values, is rhizome, which is an underground stem. The rhizome contains mainly salidroside, rosin, rosavin and p-tyrosol. There are many studies, which have reported the effects of Rhodiola spp. on different organs and health conditions. In this review, we have selected the articles from Pubmed and Google Scholar from year 1992-2016 to report the effects of Rhodiola spp. and their role in curtailing various diseases and stress. The present review emphasizes the medicinal and therapeutic applications of Rhodiola spp. on different experimental models. Overall conclusion is that Rhodiola spp. has immense therapeutic potential and hence, this review would give impetus to new research for the development of Rhodiola based herbal nutraceuticals as well as pharmaceuticals.
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Imunidade/efeitos dos fármacos , Extratos Vegetais/farmacologia , Rhodiola/química , Animais , Humanos , Raízes de Plantas/química , Plantas Medicinais/químicaRESUMO
Andrographolide, a diterpenoid, is known for its anti-inflammatory effects. It can be isolated from various plants of the genus Andrographis, commonly known as 'creat'. This purified compound has been tested for its anti-inflammatory effects in various stressful conditions, such as ischemia, pyrogenesis, arthritis, hepatic or neural toxicity, carcinoma, and oxidative stress, Apart from its anti-inflammatory effects, andrographolide also exhibits immunomodulatory effects by effectively enhancing cytotoxic T cells, natural killer (NK) cells, phagocytosis, and antibody-dependent cell-mediated cytotoxicity (ADCC). All these properties of andrographolide form the foundation for the use of this miraculous compound to restrain virus replication and virus-induced pathogenesis. The present article covers antiviral properties of andrographolide in variety of viral infections, with the hope of developing of a new highly potent antiviral drug with multiple effects.