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Histone deacetylases (HDACs) have been identified as promising targets for anticancer treatment. The study demonstrates virtual screening, molecular docking, and synthesis of 4-(2-aminoethyl) phenol derivatives as HDAC inhibitors. The virtual screening and molecular docking analysis led to the identification of 10 representative compounds, which were evaluated based on their drug-like properties. The results demonstrated that these compounds effectively interacted with the active site pocket of HDAC 3 through π-stacking, Zn2+ coordination, hydrogen bonding, and hydrophobic interactions with catalytic residues. Furthermore, a series of 4-(2-aminoethyl) phenol derivatives were synthesized, and their HDAC inhibitory activity was evaluated. Compounds 18 and 20 showed significant HDAC inhibitory activity of 64.94 ± 1.17% and 52.45 ± 1.45%, respectively, compared to the solvent control. The promising results of this study encourage further research on 4-(2-aminoethyl) phenol derivatives and may provide significant insight into the design of novel small molecule HDAC inhibitors to fight against target-specific malignancies of chronic obstructive pulmonary disease and nonsmall cell lung cancer in the future.
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Antineoplásicos , Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , Humanos , Linhagem Celular Tumoral , Simulação de Acoplamento Molecular , Fenol/farmacologia , Histona Desacetilases/metabolismo , Inibidores de Histona Desacetilases/farmacologia , Desenho de Fármacos , Antineoplásicos/química , Proliferação de Células , Relação Estrutura-Atividade , Ensaios de Seleção de Medicamentos AntitumoraisRESUMO
During the period of COVID-19, the occurrences of mucormycosis in immunocompromised patients have increased significantly. Mucormycosis (black fungus) is a rare and rapidly progressing fungal infection associated with high mortality and morbidity in India as well as globally. The causative agents for this infection are collectively called mucoromycetes which are the members of the order Mucorales. The diagnosis of the infection needs to be performed as soon as the occurrence of clinical symptoms which differs with types of Mucorales infection. Imaging techniques magnetic resonance imaging or computed tomography scan, culture testing, and microscopy are the approaches for the diagnosis. After the diagnosis of the infection is confirmed, rapid action is needed for the treatment in the form of antifungal therapy or surgery depending upon the severity of the infection. Delaying in treatment declines the chances of survival. In antifungal therapy, there are two approaches first-line therapy (monotherapy) and combination therapy. Amphotericin B (1) and isavuconazole (2) are the drugs of choice for first-line therapy in the treatment of mucormycosis. Salvage therapy with posaconazole (3) and deferasirox (4) is another approach for patients who are not responsible for any other therapy. Adjunctive therapy is also used in the treatment of mucormycosis along with first-line therapy, which involves hyperbaric oxygen and cytokine therapy. There are some drugs like VT-1161 (5) and APX001A (6), Colistin, SCH 42427, and PC1244 that are under clinical trials. Despite all these approaches, none can be 100% successful in giving results. Therefore, new medications with favorable or little side effects are required for the treatment of mucormycosis.
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COVID-19 , Mucorales , Mucormicose , Humanos , Antifúngicos/uso terapêutico , Antifúngicos/farmacologia , Mucormicose/tratamento farmacológico , Mucormicose/diagnóstico , Mucormicose/microbiologia , Anfotericina B/uso terapêutico , Anfotericina B/farmacologiaRESUMO
Since the outbreak of highly virulent coronaviruses, significant interest was assessed to the brain and heart axis (BHA) in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2)-affected patients. The majority of clinical reports accounted for unusual symptoms associated with SARS-CoV-2 infections which are of the neurological type, such as headache, nausea, dysgeusia, anosmia, and cerebral infarction. The SARS-CoV-2 enters the cells through the angiotensin-converting enzyme (ACE-2) receptor. Patients with prior cardiovascular disease (CVD) have a higher risk of COVID-19 infection and it has related to various cardiovascular (CV) complications. Infected patients with pre-existing CVDs are also particularly exposed to critical health outcomes. Overall, COVID-19 affected patients admitted to intensive care units (ICU) and exposed to stressful environmental constraints, featured with a cluster of neurological and CV complications. In this review, we summarized the main contributions in the literature on how SARS-CoV-2 could interfere with the BHA and its role in affecting multiorgan disorders. Specifically, the central nervous system involvement, mainly in relation to CV alterations in COVID-19-affected patients, is considered. This review also emphasizes the biomarkers and therapy options for COVID-19 patients presenting with CV problems.
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COVID-19 , Doenças Cardiovasculares , Cardiopatias , Humanos , SARS-CoV-2 , Encéfalo , BiomarcadoresRESUMO
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
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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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
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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The intriguing coupling phenomena among spin, phonon, and charge degrees of freedom in materials having magnetic, ferroelectric and/or ferroelastic order have been of research interest for the fundamental understanding and technological relevance. We report a detailed study on structure and phonons of Al0.5Ga0.5FeO3 (ALGF), a lead-free magnetoelectric material, carried out using variable temperature dependent powder neutron diffraction and Raman spectroscopy. Neutron diffraction studies suggest that Al3+ ions are distributed in one tetrahedrally (BO4) and three octahedrally (BO6) coordinated sites of the orthorhombic (Pc21n) structure and there is no structural transition in the temperature range of 7-800 K. Temperature dependent field-cooled and zero-field-cooled magnetization studies indicate ferrimagnetic ordering below 225 K (TN), and that is reflected in the low temperature powder neutron diffraction data. An antiferromagnetic type arrangement of Fe3+ ions with net magnetic moment of 0.13 µB/Fe3+ was observed from powder neutron diffraction analysis and it corroborates the findings from magnetization studies. At the magnetic transition temperature, no drastic change in lattice strain was observed, while significant changes in phonons were observed in the Raman spectra. The deviation of several mode frequencies from the standard anharmonicity model in the ferrimagnetic phase (below 240 K) is attributed to coupling effect between spin and phonon. Spin-phonon coupling effect is discernable from Raman bands located at 270, 425, 582, 695, 738, and 841 cm-1. Their coupling strengths (λ) have been estimated using our phonon spectra and magnetization results. BOn (n = 4, 6) libration (restricted rotation) mode at 270 cm-1 has the largest coupling constant (λâ¼ 2.3), while the stretching vibrations located at 695 and 738 cm-1 have the lowest coupling constant (λâ¼ 0.5). In addition to the libration mode, several internal stretching and bending modes of polyhedral units are strongly affected by spin ordering.
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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
Pesticidal properties of Bacillus thuringiensis and its associated toxic proteins is an ever-growing science with potential implications in biological pest management. In the present study 80 Bacillus thuringiensis isolates native to Uttarakhand Himalayas were evaluated for chitinolytic activity and potent ones (11 isolates) were further subjected to multiphasic characterization for their antifungal, insecticidal and synergistic properties with selected chemical insecticides. Although all the 11 potent isolates were biologically active, only three isolates (VLBt27, VLBt109 and VLBt238) showed >90% inhibition in radial growth of 3 out of 4 tested plant pathogenic fungi (Rhizoctonia solani, Fusarium oxysporum, Alternaria pori and Pyricularia oryzae). The key antagonism was manifested in the form of disruptions in growing tips and uneven mycelial thickenings. In insect bioassays (against Helicoverpa armigera, Mythimna separata and Thysanoplusia orichalcea), no considerable direct mortality was observed. However, the larval weight reduction was prominent in four isolates (VLBt27, VLBt38, VLBt109 and VLBt135) which accounts to >75% in first instar larvae of H. armigera. Joint action of these four isolates with chemical insecticides showed an overall additive interaction against Brevicoryne brassicae and synergism against H. armigera. All the isolates were compatible with tested insecticides at their field recommended doses except for chlorpyriphos with around 130â¯kDa protein as chitinase. The study identified VLBt27 and VLBt109, two native isolates of B. thuringiensis with potential antagonistic activity and synergism as well. These isolates have possible implications as single strategy against two diverse pest problems (pathogenic fungi and phytophagous insect) of agriculture with a view of reduced pesticide application.
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Bacillus thuringiensis/fisiologia , Inseticidas/farmacologia , Mariposas/efeitos dos fármacos , Animais , Quitinases/metabolismo , Controle Biológico de VetoresRESUMO
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
By means of numerical simulations, using a computational fluid dynamics software together with an optical ray tracing analysis platform, we show that we can tune various optical aberrations by electrically manipulating the shape of liquid lenses using one hundred individually addressable electrodes. To demonstrate the flexibility of our design, we define electrode patterns based on specific Zernike modes and show that aspherical, cylindrical and decentered shapes of liquid lenses can be produced. Using different voltages, we evaluate the tuning range of spherical aberration (Z11), astigmatism (Z5 and Z6) and coma (Z7), while a hydrostatic pressure is applied to control the average curvature of a microlens with a diameter of 1mm. Upon activating all electrodes simultaneously spherical aberrations of 0.15 waves at a pressure of 30Pa can be suppressed almost completely for the highest voltages applied. For astigmatic and comatic patterns, the values of Z5, Z6 and Z7 increase monotonically with the voltage reaching values up to 0.06, 0.06 and 0.2 waves, respectively. Spot diagrams, wavefront maps and modulation transfer function are reported to quantify the optical performance of each lens. Crosstalk and independence of tunability are discussed in the context of possible applications of the approach for general wavefront shaping.
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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.
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Andrographis/química , Antivirais/farmacologia , Diterpenos/farmacologia , Extratos Vegetais/farmacologia , Viroses/virologia , Vírus/efeitos dos fármacos , Animais , Humanos , Estresse Oxidativo , Viroses/tratamento farmacológicoRESUMO
The changes in chemical composition, antioxidant activity and fatty acid composition of lentil flour after dehulling, germination and cooking of seeds were investigated. Dehulling showed no significant effect on protein content, however, protein content decreased in most of the varieties after germination and cooking. Total soluble sugars (TSS) content increased significantly after dehulling (2.0-41.64 %) and cooking (2.08-31.07 %) whereas, germination had no significant effect on TSS content. Total lipids increased significantly after dehulling (21.56-42.86 %) whereas, it decreased significantly after germination (2.97-26.52 %) and cooking (23.05-58.63 %). Cooking was more effective than other methods in reducing trypsin inhibitors (80.51-85.41 %). Dehulling was most effective in reducing tannins (89.46-92.99 %) and phytic acid (52.63-60.00 %) content over raw seed. Myristic, palmitic, stearic, oleic and linoleic acid content decreased while linolenic acid content increased after dehulling. Dehulling, germination and cooking decreased the content of antioxidant metabolite (gallic acid, catechin and quercetin) and also antioxidant activities. Raw samples followed by germinated samples showed the highest concentrations of phytochemicals responsible for antioxidant activity and also the antioxidant capacities. Present study showed germination and cooking would be useful in formulation and development of lentil based functional foods for human health benefits.
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We propose a new design for tuning the astigmatism of liquid micro-lenses using electric field and hydrostatic pressure as control parameters. We explore the feasibility and operating range of the lens with a self-consistent numerical calculation of the electric field distribution and the shape of the two-phase interface. Equilibrium shapes, including surface profiles parallel and perpendicular to a stripe electrode, are extracted to determine the astigmatism. The wavefronts are decomposed into Zernike polynomials under zero defocus conditions using a commercial ray-tracing software. We observe that the global curvature of the lens is primarily controlled by the hydrostatic pressure, while asphericity and astigmatism are controlled by the electric field. For optimized electrode geometries and simultaneous control of pressure and electric fields the astigmatism can be tuned from Z6 = 0 0.38 µm with minor changes in the focal length.
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Dengue is an arboviral disease with no effective therapy available. Therefore, there is an urgent need to find a potent antiviral agent against dengue virus (DENV). In the present study, salidroside, a main bioactive compound of Rhodiola rosea, was evaluated for its antiviral potential against DENV serotype-2 infection and its effect on host innate immune factors. Antiviral effects of salidroside were examined in DENV-infected cells by western blotting, flow cytometry and real-time PCR. Its underlying mechanism involved in antiviral action was determined by evaluating expression of host innate immune factors including RIG-I, IRF-3, IRF-7, PKR, P-eIF2α and NF-κB. Salidroside potently inhibited DENV infection by decreasing DENV envelope protein expression more than tenfold. Salidroside exerts its antiviral activity by increasing expression of RNA helicases such as RIG-I, thereby initiating a downstream signaling cascade that induces upregulation of IRF-3 and IRF-7. It prevents viral protein synthesis by increasing the expression of PKR and P-eIF2α while decreasing NF-κB expression. It was also found to induce the expression of IFN-α. In addition, the number of NK cells and CD8+ T cells were also found to be increased by salidroside treatment in human PBMCs, which are important in limiting DENV replication during early stages of infection. The findings presented here suggest that salidroside exhibits antiviral activity against DENV by inhibiting viral protein synthesis and boosting host immunity by increasing the expression of host innate immune factors and hence could be considered for the development of an effective therapeutic agent against DENV infection.
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Antivirais/metabolismo , Vírus da Dengue/efeitos dos fármacos , Vírus da Dengue/imunologia , Glucosídeos/metabolismo , Fatores Imunológicos/biossíntese , Fatores Imunológicos/metabolismo , Fenóis/metabolismo , Proteínas Virais/antagonistas & inibidores , Linhagem Celular , Células Cultivadas , Perfilação da Expressão Gênica , Glucosídeos/isolamento & purificação , Humanos , Monócitos/imunologia , Monócitos/virologia , Fenóis/isolamento & purificação , Rhodiola/química , Proteínas Virais/biossínteseRESUMO
High altitude hypoxia is known to induce an inflammatory response in immune cells. Hypoxia induced inflammatory chemokines may contribute to the development of high altitude pulmonary edema (HAPE) by causing damage to the lung endothelial cells and thereby capillary leakage. In the present study, we were interested to know whether chronic inflammation may contribute to HAPE susceptibility. We examined the serum levels of macrophage inflammatory protein-1α (MIP-1α), monocyte chemoattractant protein-1 (MCP-1) and interleukin-8 in group (1) HAPE Susceptible subjects (n = 20) who had past history of HAPE and group (2) Control (n = 18) consist of subjects who had stayed at high altitude for 2 years without any history of HAPE. The data obtained confirmed that circulating MCP-1, MIP-1α were significantly upregulated in HAPE-S individuals as compared to the controls suggestive of chronic inflammation. However, it is not certain whether chronic inflammation is cause or consequence of previous episode of HAPE. The moderate systemic increase of these inflammatory markers may reflect considerable local inflammation. The existence of enhanced level of inflammatory chemokines found in this study support the hypothesis that subjects with past history of HAPE have higher baseline chronic inflammation which may contribute to HAPE susceptibility.
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The hypoxic preconditioning of mammalian cells has been shown to have beneficial effects against hypoxic injuries. However, very little information is available on the comparative analysis of immunological responses to hypoxic and hypoxia mimetic exposure. Therefore, in the present study, mouse peritoneal macrophages and splenocytes were subjected to hypoxia exposure (0.5 % O2) and hypoxia mimetic Cobalt chloride (CoCl2) treatment to evaluate their effect on immune response and delineate the underlying signaling mechanisms. The results obtained indicated that super oxide generation increased while TLR4 expression and cell surface markers like CD25, CD40 and CD69 were suppressed in both the treatments as compared to normoxia. Cobalt chloride treatment increased NF-κB expression, nitric oxide (NO) and iNOS expression, cytokines TNF-α and IL-6 as compared to hypoxia exposure. Our study showed that CoCl2 stabilizes HIF-1α to create hypoxia like conditions but it mainly influences the inflammatory response via NF-κB signaling pathway by skewing the production of proinflammatory molecules like TNF-α, IL-6 and NO.