Immunomodulatory and immune-toxicological role of nanoparticles: Potential therapeutic applications.

Nowadays, Nanoparticle-based immunotherapeutic research has invoked global interest due to their unique properties. The immune system is a shielding structure that defends living things from external threats. Before the use of any materials in drug design, it is essential to study the immunological response to avoid triggering undesirable immune responses in the body. This review tries to summarize the properties, various applications, and immunotherapeutic aspects of NP-induced immunomodulation relating to therapeutic development and toxicity in human health. The role of NPs in the immune system and their modulatory functions, resulting in immunosuppression or immunostimulation, exerts benefits or dangers depending on their compositions, sizes, surface chemistry, and so forth. After NPs enter into the body, they can interact with body fluid exposing, them to different body proteins to form protein corona particles and other bio-molecules (DNA, RNA, sugars, etc.), which may alter their bioactivity. Phagocytes are the first immune cells that can interact with foreign materials including nanoparticles. Immunostimulation and immunosuppression operate in two distinct manners. Overall, functionalized nanocarriers optimized various therapeutic implications by stimulating the host immune system and regulating the tranquility of the host immune system. Among others, toxicity and bio-clearance of nanomaterials are always prime concerns at the preclinical and clinical stages before final approval. The interaction of nanoparticles with immune cells causes direct cell damage via apoptosis and necroses as well as immune signaling pathways also become influenced.

Liposomes to Cubosomes: The Evolution of Lipidic Nanocarriers and Their Cutting-Edge Biomedical Applications.

Lipidic nanoparticles have undergone extensive research toward the exploration of their diverse therapeutic applications. Although several liposomal formulations are in the clinic (e.g., DOXIL) for cancer therapy, there are many challenges associated with traditional liposomes. To address these issues, modifications in liposomal structure and further functionalization are desirable, leading to the emergence of solid lipid nanoparticles and the more recent liquid lipid nanoparticles. In this context, "cubosomes", third-generation lipidic nanocarriers, have attracted significant attention due to their numerous advantages, including their porous structure, structural adaptability, high encapsulation efficiency resulting from their extensive internal surface area, enhanced stability, and biocompatibility. Cubosomes offer the potential for both enhanced cellular uptake and controlled release of encapsulated payloads. Beyond cancer therapy, cubosomes have demonstrated effectiveness in wound healing, antibacterial treatments, and various dermatological applications. In this review, the authors provide an overview of the evolution of lipidic nanocarriers, spanning from conventional liposomes to solid lipid nanoparticles, with a special emphasis on the development and application of cubosomes. Additionally, it delves into recent applications and preclinical trials associated with cubosome formulations, which could be of significant interest to readers from backgrounds in nanomedicine and clinicians.

Enhancing Immunological Memory: Unveiling Booster Doses to Bolster Vaccine Efficacy Against Evolving SARS-CoV-2 Mutant Variants.

A growing number of re-infections with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) in previously immunized individuals has sparked discussions about the potential need for a booster vaccine dosage to counteract declining antibody levels and new strains. The protective immunity produced by vaccinations, and past illnesses relies on immunological memory. CD4 + T cells, CD8 + T cells, B cells, and long-lasting antibody responses are all components of the adaptive immune system that can generate and maintain this immunological memory. Since novel mutant variants have emerged one after the other, the world has been hit by repeated waves. Various vaccine formulations against SARS-CoV-2 have been administered across the globe. Thus, estimating the efficacy of those vaccines against gradually developed mutant stains is the essential parameter regarding the fate of those vaccine formulations and the necessity of booster doses and their frequency. In this review, focus has also been given to how vaccination stacks up against moderate and severe acute infections in terms of the longevity of the immune cells, neutralizing antibody responses, etc. However, hybrid immunity shows a greater accuracy of re-infection of variants of concern (VOCs) of SARS-CoV-2 than infection and immunization. The review conveys knowledge of detailed information about several marketed vaccines and the status of their efficacy against specific mutant strains of SARS-CoV-2. Furthermore, this review discusses the status of immunological memory after infection, mixed infection, and vaccination.

Self-assembled renewable nano-sized pentacyclic triterpenoid maslinic acids in aqueous medium for anti-leukemic, antibacterial and biocompatibility studies: An insight into targeted proteins-compound interactions based mechanistic pathway prediction through molecular docking.

Maslinic acid is a naturally occurring dihydroxy, mono-carboxy bioactive triterpenoid. Its bulky structure was the main hindrance in the path of biological activity. Sodium and potassium salts of nano-sized triterpenoid maslinic acid were prepared from maslinic acid and its self-assembly property was studied in aqueous and aqueous-organic binary liquid mixtures. Morphology of the compounds studied by Field Emission Scanning Electron Microscopy (FESEM), Atomic Force Microscopy (AFM), High Resolution Transmission Electron Microscopy (HRTEM), Optical Microscopy, Fourier Transform Infrared Spectroscopy (FTIR) and X-ray diffraction (XRD) revealed vesicular morphology of the self-assemblies. Selective cytotoxicity was performed in leukemic (K-562 and KG-1a) and PBMC cells. Among the three self-assemblies (maslinic acid 1, sodium maslinate 2 and potassium maslinate 3), sodium maslinate 2 showed better antileukemic efficacy. Sodium maslinate 2 induced apoptosis in leukemic cells by elevating ROS levels and disrupting the cellular antioxidant system. From the in-silico studies, it was confirmed that 2 interacted with extrinsic and intrinsic apoptotic proteins of leukemic cells and killed those cells by inducing apoptotic pathways. The compounds 1, 2 and 3 showed significant antibacterial efficacy against E.coli strain through binding with several periplasmic membrane fusion protein (MFP) and limiting the efflux system leading to arrestation of antimicrobial resistance.

Bioactive Pentacyclic Triterpenes Trigger Multiple Signalling Pathways for Selective Apoptosis Leading to Anticancer Efficacy: Recent Updates and Future Perspectives.

Nowadays, discovering an effective and safe anticancer medication is one of the major challenges. Premature death due to the unidirectional toxicity of conventional therapy is common in cancer patients with poor health status. Plants have been used as medicine since prehistoric times, and extensive research on the anticancer properties of various bioactive phytomolecules is ongoing. Pentacyclic triterpenoids are secondary metabolites of plants with well-known cytotoxic and chemopreventive properties established in numerous cancer research studies. The lupane, oleanane, and ursane groups of these triterpenoids have been well-studied in recent decades for their potential antitumor activity. This review delves into the molecular machinery governing plant-derived triterpenes' anticancer efficacy. The highlighted mechanisms are antiproliferative activity, induction of apoptosis through regulation of BCL-2 and BH3 family proteins, modulation of the inflammatory pathway, interference with cell invagination and inhibition of metastasis. Lack of solubility in mostly used biological solvents is the major barrier to the therapeutic progress of these triterpenoids. This review also highlights some probable ways to mitigate this issue with the help of nanotechnology and the modification of their physical forms.

Modulatory role of miRNAs in thyroid and breast cancer progression and insights into their therapeutic manipulation.

Over the past few decades, thyroid cancer has become one of the most common types of endocrine cancer, contributing to an increase in prevalence. In the year 2020, there were 586,202 newly diagnosed cases of thyroid cancer around the world. This constituted approximately 3.0% of all patients diagnosed with cancer. The World Health Organization reported that there will be 2.3 million women receiving treatment for breast cancer in 2020, with 685,000. Despite the fact that carcinoma is one of the world's leading causes of death, there is still a paucity of information about its biology. MicroRNAs (miRNAs; miRs) are non-coding RNAs that can reduce gene expression by cleaving the 3' untranslated regions of mRNA. These factors make them a potential protein translation inhibitor. Diverse biological mechanisms implicated in the genesis of cancer are modulated by miRNA. The investigation of global miRNA expression in cancer showed regulatory activity through up regulation and down-regulation in several cancers, including thyroid cancer and breast cancer. In thyroid cancer, miRNA influences several cancers related signaling pathways through modulating MAPK, PI3K, and the RAS pathway. In breast cancer, the regulatory activity of miRNA was played through the cyclin protein family, protein kinases and their inhibitors, and other growth promoters or suppressors, which modulated cell proliferation and cell cycle progression. This article's goal is to discuss key miRNA expressions that are involved in the development of thyroid and breast cancer as well as their therapeutic manipulation for these two specific cancer types.

Antibacterial potency of cytocompatible chitosan-decorated biogenic silver nanoparticles and molecular insights towards cell-particle interaction.

In the study, leaf extract of Carica papaya was utilized for the biogenic fabrication process of chitosan functionalized silver nanoparticles (Ag-Chito NPs). HRTEM analysis revealed that the fabricated Ag-Chito NPs was spherical in shape, with an average particle size of 13.31 (±0.07) nm. FTIR, UV-Vis, DLS, and other characterizations were also performed to analyze the diverse physicochemical properties of the particles. The antibacterial potency of the synthesized Ag-Chito NPs was tested against the two clinically isolated multidrug resistant uropathogenic bacterial strains, i.e. MLD 2 (Escherichia coli) and MLD 4 (Staphylococcus aureus) through MIC, MBC, time and concentration dependent killing kinetic assay, inhibition of biofilm formation assay, fluorescence and SEM imaging. Significantly, Ag-Chito NPs showed the highest sensitivity against the MLD 2 (MIC value of 12.5 µg/mL) strain, as compared to the MLD 4 (MIC value of 15 µg/mL) strain. From the hemolysis assay, it was revealed that Ag-Chito NPs exerted no significant toxicity up to 50 µg/mL against healthy human blood cells. Additionally, in silico analysis of chitosan (functionalized on the surface of AgNPs) and bacterial cell membrane protein also evidently suggested a strong interaction between Ag-Chito NPs and bacterial cells, which might be responsible for bacterial cell death.

Self-Assembled Maslinic Acid Attenuates Doxorobucin Induced Cytotoxicity via Nrf2 Signaling Pathway: An In Vitro and In Silico Study in Human Healthy Cells.

The clinical applications of some well-known chemotherapeutic drugs for cancer treatment have been restricted nowadays owing to their adverse effects on many physiological systems. In this experimental study, maslinic acid (MA) isolated from Olea europaea (Olive) fruit extract was used to mitigate the cytotoxicity induced by Doxorubicin (DOX) in human healthy peripheral blood mononuclear cells (hPBMCs). Self-assembled maslinic acid (SA-MA) was obtained in ethanol-water mixture (35.5 mM: 4:1 v/v). The morphology of SA-MA was analyzed by various physicochemical characterization techniques, which revealed its micro-metric vesicular architecture as well as nano-vesicular appearances. In this study, treatment of hPBMCs with DOX has been found to generate severe intracellular oxidative stress, which was significantly mitigated after pre-treatment with SA-MA. Alteration of hPBMC morphologies after DOX treatment was also restored notably by pre-treatment with SA-MA. Furthermore, pentoxifylline (TNF-α inhibitor) and indomethacin (COX-2 inhibitor) were used to investigate the responsible pathway by which SA-MA protected hPBMCs from DOX-induced cellular stress. Restoration of hPBMC viability above 92% in both cases confirmed that SA-MA protected the cells by inhibiting inflammatory pathways generated by DOX treatment. Subsequently, in molecular docking study, it was also evaluated that MA could successfully bind with the pocket region of Keap1, while Nrf2 was capable of upregulating cytoprotecting genes.

Is Omicron the end of pandemic or start of a new innings?

In the middle of November 2021, Omicron (B.1.1.529), a novel variant of SARS-CoV-2 was identified in South Africa. Owing to continuous increasing cases with rapid transmissibility and immune evasion, the World Health Organization (WHO) has categorized this strain as a variant of concern (VOC). In total, over 60 mutations have been identified in Omicron (BA.1) and latterly, its three sub-lineages (BA.1.1, BA.2, and BA.3) have also been found with additional mutations and pathogenicity. The highly contagious Omicron causes less severe sickness than Delta, but it is still dangerous for those who have not been vaccinated. Following the unique identification of the Omicron variant, a fresh debate has erupted regarding the natural vaccines. A number of experts believe that Omicron can work as a natural vaccine, because it is similar to live attenuated vaccines in certain ways. Additionally, it was highlighted that the high rate of antibody generation in individuals cured of Omicron provide suggestive evidence in favor of those researchers who claimed Omicron acts as natural vaccine. Some disagreements also noted, as it also has tremendous health effects and high infection rate, as similar to the prior variants. This review summarizes the contradictory scenario among the scientists about Omicron variant.

Alteration of dietary habits and lifestyle pattern during COVID-19 pandemic associated lockdown: An online survey study.

BACKGROUND & AIM: A few population-based studies have looked at how the Corona virus disease (COVID-19) pandemic and outbreak-related lockdown has impacted people's daily eating habits and lifestyles. Due to the emergence of the Severe Acute Respiratory Syndrome Corona Virus 2 (SARS-CoV-2), continuous lockdown or social isolation can alter dietary consumption patterns and lifestyle routines, resulting in significant negative health consequences. Focused on the COVID-19 and disease related lockdown effects, this study aims to reflect the evolving trend in dietary habits and lifestyle status during the COVID-19 lockdown in West Bengal through a population mediated retrospective survey distributed via social media platforms. METHODS: This survey was conducted using Google form via online platform from July 7 to July 31, 2020, with 1059 participants reported their eating habits and lifestyle preferences, as well as basic socio-demographic details. Entire variables were qualitatively examined and uttered as frequency (f) and percentage (%). The Chi-square test was performed to conclude whether categorical variables differed. RESULTS: A high number of participants reported that they were consumed healthy foods and physically active during this pandemic situation. Females were more likely to be involved in exercise and consume protein-rich food, as well as the majority of them, maintain basic dietary and Ayurvedic home remedies precautions like consumption of lemon, consumption of herbs, taking warm water, etc. A majority of older participants were tried to maintain a healthy lifestyle with extra protective essential protection during the COVID-19 stage. The frequency of going to market was decreased by the participants. Females were more likely to decrease their frequency of going to market than males. In terms of hygiene and sanitization of food items after buying from the market, females were more careful than males. Participants with higher education were more likely to be careful regarding the hygiene of food preparation and eating during this situation. CONCLUSION: From this study, dieticians, legislators, and public health experts can have a better understanding of the current situation of food intake and lifestyle trends in communities of West Bengal, India. It also has the potential to have a significant impact on future public health research.

Immunogenic and reactogenic efficacy of Covaxin and Covishield: a comparative review.

SARS-CoV-2 is an RNA virus that was identified for the first time in December 2019 in Wuhan, China. The World Health Organization (WHO) labeled the novel coronavirus (COVID-19) outbreak a worldwide pandemic on March 11, 2020, due to its widespread infectivity pattern. Because of the catastrophic COVID-19 outbreak, the development of safe and efficient vaccinations has become a key priority in every health sector throughout the globe. On the 13th of January 2021, the vaccination campaign against SARS-CoV-2 was launched in India and started the administration of two types of vaccines known as Covaxin and Covishield. Covishield is an adenovirus vector-based vaccine, and Covaxin was developed by a traditional method of vaccine formulation, which is composed of adjuvanted inactivated viral particles. Each vaccine's utility or efficiency is determined by its formulation, adjuvants, and mode of action. The efficacy of the vaccination depends on numeral properties like generation antibodies, memory cells, and cell-mediated immunity. According to the third-phase experiment, Covishield showed effectiveness of nearly 90%, whereas Covaxin has an effectiveness of about 80%. Both vaccination formulations in India have so far demonstrated satisfactory efficacy against numerous mutant variants of SARS-CoV-2. The efficacy of Covishield may be diminished if the structure of spike (S) protein changes dramatically in the future. In this situation, Covaxin might be still effective for such variants owing to its ability to produce multiple antibodies against various epitopes. This study reviews the comparative immunogenic and therapeutic efficacy of Covaxin and Covishield and also discussed the probable vaccination challenges in upcoming days.

Awareness, knowledge and acceptance of COVID-19 vaccine among the people of West Bengal, India: A web-based survey.

Objectives: Rapid vaccination is the only way to fight against COVID-19.Vaccine hesitancy is the major barrier against this strategy. The main objective of this cross-sectional study was to analyze COVID-19 vaccine acceptance in the general population of West Bengal (India), as well as to investigate the factors that were independently associated with people's desire to receive the vaccine. Methods: An online questionnaire was distributed by email, Whatsapp, and other social media platforms, and the responses were analyzed using the SPSS (Version 20) software. Results: We conducted a web-based survey in West Bengal, India (N = 803), and accumulated information on individuals' desire to adopt vaccine against COVID-19, views about the virus's effectiveness, and many knowledge-based socio-demographic factors that potentially impact the overall vaccination efforts. We found that, 12.08% of participants do not believe that vaccination against COVID-19 is necessary, but among the rest of the population, 44.33% of individuals are willing to be vaccinated once the vaccine is available, whereas 39.60% of the population responded that they will not be vaccinated immediately but will do so later. Conclusions: Despite the participants' strong vaccine willingness, our findings revealed a troubling degree of lake of awareness and insignificant scientific knowledge about the COVID-19 pandemic and its associated vaccination programme. Vaccination hesitancy is not a barrier in this survey region, but poor vaccine availability and a lack of awareness campaigns may instill unfavorable beliefs in those who refuse to be vaccinated.

OBJETIVOS: La rapidez de la vacunación es el único modo de luchar contra la COVID-19. Las dudas sobre la vacuna constituyen la mayor barrera contra esta estrategia. El objetivo principal de este estudio transversal fue analizar la aceptación de la vacuna contra la COVID-19 en la población general de Bengala occidental (India), así como investigar los factores asociados de manera independiente al deseo de recibir la vacuna por parte de las personas.Métodos: Se distribuyó un cuestionario online por correo electrónico, Whatsapp, y otras plataformas de redes sociales, y se analizaron las respuestas utilizando el software SPSS (Versión 20). RESULTADOS: Realizamos una encuesta basada en web en Bengala occidental, India (N= 803), y acumulamos la información sobre el deseo de las personas de recibir la vacuna contra la COVID-19, las opiniones sobre la efectividad del virus, y muchos factores sociodemográficos basados en el conocimiento que tienen un impacto potencial en los esfuerzos globales sobre vacunación. Encontramos que el 12,08% de los participantes no creen en la necesidad de la vacunación contra la COVID-19 pero, entre el resto de la población, el 44,33% de los individuos desean ser vacunados una vez que se disponga de la vacuna, mientras que el 39,6% de la población respondió que no se vacunarían de inmediato, aunque lo harían más adelante. CONCLUSIONES: A pesar de la sólida voluntad de los participantes por la vacuna, nuestros hallazgos revelaron un grado preocupante de falta de concienciación y conocimiento científico insignificante acerca de la pandemia de COVID- 19 y su programa de vacunación asociado. Las dudas sobre la vacuna no son una barrera en la región de esta encuesta, pero la poca disponibilidad de la vacuna y la falta de campañas de concienciación puede infundir creencias desfavorables en aquellas personas que rechazan recibir la vacuna.

Advancements in Adjuvanticity of Bioactive Inorganic and Organic Compounds.

BACKGROUND: Regardless of the enormous success of vaccines over decades, the formulation of biocompatible and highly effective vaccines is still insufficient for combating new pathogens. DISCUSSION: The degree of effectiveness of any vaccine largely depends on the choice of appropriate adjuvant. Along with the optimum biocompatibility, an ideal adjuvant must be biodegradable, economical and easy to manufacture. To date, various organic and inorganic substances have been used as an adjuvant to augment the effectiveness of the vaccine. Immunological adjuvants are essential for strong and long-term effects against various pathogens. However, a very limited number of licensed adjuvants are available for the formulation of a successful vaccine. This leads to a challenging situation in medical science. CONCLUSION: The present review concisely summarizes the mechanism of action of various bioactive organic and inorganic immunological adjuvants, their limitations and future perspectives for their appropriate modification. Current trends of anticancer therapies using immunological adjuvants have also been highlighted in this review.

Rapid Green Synthesis of Biogenic Silver Nanoparticles Using Cinnamomum tamala Leaf Extract and its Potential Antimicrobial Application Against Clinically Isolated Multidrug-Resistant Bacterial Strains.

Cinnamomum tamala is Indian bay leaves also known as Tej patta commonly used in the preparation of delicious food for its sweet aroma and tremendous medicinal values. In this study, the significant concentration-dependent free radical scavenging and antioxidant efficacy of the aqueous extracts of bay leaves has been determined using DPPH (2, 2-diphenyl-l-picrylhydrazyl) radical scavenging, ferric ion-reducing power assay, and hydrogen peroxide radical scavenging assay. The leaf extract has also been utilized in the rapid synthesis of silver nanoparticles (AgNPs) under mild conditions (30 min reaction time at 70 °C) without the addition of extra stabilizing or capping agents. Mostly spherical shaped particles were formed with diameter ranging from 10 to 12 nm as evident by HRTEM imaging. The silver nanoparticles were also characterized using FTIR, XRD, and UV-visible spectroscopic techniques. The antibacterial effect of the synthesized AgNPs was studied against three clinically isolated multidrug-resistant bacterial strains (Escherichia coli (EC-1), Klebsiella pneumonia (KP-1), and Staphylococcus aureus (SA-1)). The minimum inhibitory concentration (MIC) and minimum bactericidal concentration (MBC) of AgNPs against EC-1 were 12.5 and 15 µg/mL and in SA-1 were 10 and 50 µg/mL, and in the case of KP-1, both values were 12.5 µg/mL. It was also noted that 8 h treatment duration using AgNPs was sufficient to eliminate all types of bacterial growth as evidenced by time-dependent killing kinetic assays. The biocompatibilities of AgNPs were also tested against human health RBCs, and it was observed that it did not show any significant toxicity up to 50 µg/mL concentration.

Chronic hyperglycemia mediated physiological alteration and metabolic distortion leads to organ dysfunction, infection, cancer progression and other pathophysiological consequences: An update on glucose toxicity.

Chronic exposure of glucose rich environment creates several physiological and pathophysiological changes. There are several pathways by which hyperglycemia exacerbate its toxic effect on cells, tissues and organ systems. Hyperglycemia can induce oxidative stress, upsurge polyol pathway, activate protein kinase C (PKC), enhance hexosamine biosynthetic pathway (HBP), promote the formation of advanced glycation end-products (AGEs) and finally alters gene expressions. Prolonged hyperglycemic condition leads to severe diabetic condition by damaging the pancreatic ß-cell and inducing insulin resistance. Numerous complications have been associated with diabetes, thus it has become a major health issue in the 21st century and has received serious attention. Dysregulation in the cardiovascular and reproductive systems along with nephropathy, retinopathy, neuropathy, diabetic foot ulcer may arise in the advanced stages of diabetes. High glucose level also encourages proliferation of cancer cells, development of osteoarthritis and potentiates a suitable environment for infections. This review culminates how elevated glucose level carries out its toxicity in cells, metabolic distortion along with organ dysfunction and elucidates the complications associated with chronic hyperglycemia.

Induction profiles of mRNA of toll like receptors and cytokines in chickens pre-exposed to low pathogenic avian influenza H9N2 virus followed by challenge with highly pathogenic avian influenza H5N1 virus.

Herein, the induction of TLRs and cytokines in chickens pre-exposed to low pathogenic avian influenza H9N2 virus followed by challenge with highly pathogenic avian influenza (HPAI) H5N1 virus was studied. Four groups (1-4) of chickens inoculated with 106 EID50 of H9N2 virus were challenged with 106 EID50 of H5N1 virus on days 1, 3, 7 and 14 post H9N2 inoculation, respectively. In groups (1-4) TLRs and cytokines induction was studied in chicken PBMCs on day 3 post H5N1 challenge. In H5N1 control group TLRs (1, 2, 5 and 7) cytokines (IFNα, IFNß, IFNγ, IL1ß, IL2, IL4, IL8 and TGF ß3) were down regulated. In group 1 down regulation of cytokines and TLRs was similar to H5N1 control birds. Down regulation of TLRs and cytokines in H5N1 control and group 1 resulted death of all the chickens. In group 2, up-regulation of TLRs (3, 7 and 15) and induction of TNFα, IFNα, IFNß, IFNγ aided virus clearance leading to survival of all the chickens. In group 3 significant up-regulation of TLRs (3, 4 and 15) and significant induction of cytokines (IFNγ, TNFα, IL1ß, IL4, IL6, IL8, IL10 and TGF ß3) was detected. In group 4 significant up-regulation of TLRs (2, 3, 7 and 15) and significant induction of cytokines (IFNγ, TNFα, IL1ß, IL2, IL6, IL8 and IL10) was detected. In groups 3 and 4 simultaneous and significant induction of pro-inflammatory, antiviral and anti-inflammatory cytokine resulted cytokine dysregulation leading to death of (2/6) and (3/6) chickens respectively. Hence, the study revealed TLRs and cytokines role in modulating the H5N1 infection outcome in chickens pre-exposed to H9N2 virus.

Surface modification minimizes the toxicity of silver nanoparticles: an in vitro and in vivo study.

Currently toxicological research in Silver nanoparticle is a leading issue in medical science. The surface chemistry and physical dimensions of silver nanoparticles (Ag-NPs) play an important role in toxicity. The aim of this present study was to evaluate the in vitro and in vivo toxicity of Ag-NPs as well as the alteration of toxicity profile due to surface functionalization (PEG and BSA) and the intracellular signaling pathways involved in nanoparticles mediated oxidative stress and apoptosis in vitro and in vivo system. Ag-NPs released excess Ag+ ions leads to activation of NADPH oxidase and helps in generating the reactive oxygen species (ROS). Silver nanoparticles elicit the production of excess amount of ROS results activation of TNF-α. Ag-NPs activates caspase-3 and 9 which are the signature of mitochondrial pathway. Ag-NPs are responsible to decrease the antioxidant enzymes and imbalance the oxidative status into the cells but functionalization with BSA and PEG helps to protect the adverse effect of Ag-NPs on the cells. This study suggested that Ag-NPs are toxic to normal cells which directly lead with human health. Surface functionalization may open the gateway for further use of Ag-NPs in different area such as antimicrobial and anticancer therapy, industrial use or in biomedical sciences.

Highly pathogenic avian influenza H5N1 virus induces cytokine dysregulation with suppressed maturation of chicken monocyte-derived dendritic cells.

One of the major causes of death in highly pathogenic avian influenza virus (HPAIV) infection in chickens is acute induction of pro-inflammatory cytokines (cytokine storm), which leads to severe pathology and acute mortality. DCs and respiratory tract macrophages are the major antigen presenting cells that are exposed to mucosal pathogens. We hypothesized that chicken DCs are a major target for induction of cytokine dysregulation by H5N1 HPAIV. It was found that infection of chicken peripheral blood monocyte-derived dendritic cells (chMoDCs) with H5N1 HPAIV produces high titers of progeny virus with more rounding and cytotoxicity than with H9N2 LPAIV. Expression of maturation markers (CD40, CD80 and CD83) was weaker in both H5N1 and H9N2 groups than in a LPS control group. INF-α, -ß and -γ were significantly upregulated in the H5N1 group. Pro-inflammatory cytokines (IL-1ß, TNF-α and IL-18) were highly upregulated in early mid (IL-1), and late (IL-6) phases of H5N1 virus infection. IL-8 (CXCLi2) mRNA expression was significantly stronger in the H5N1 group from 6 hr of infection. TLR3, 7, 15 and 21 were upregulated 24 hr after infection by H5N1 virus compared with H9N2 virus, with maximum expression of TLR 3 mRNA. Similarly, greater H5N1 virus-induced apoptotic cell death and cytotoxicity, as measured by terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling and lactate dehydrogenase assays, respectively, were found. Thus, both H5N1 and H9N2 viruses evade the host immune system by inducing impairment of chMoDCs maturation and enhancing cytokine dysregulation in H5N1 HPAIV-infected cells.