Poly-ß-thioester-Based Cross-Linked Nanocarrier for Cancer Cell Selectivity over Normal Cells and Cellular Apoptosis by Triggered Release of Parthenolide, an Anticancer Drug.

Breast cancer is the most prevalent and aggressive type of cancer, causing high mortality rates in women globally. Many drawbacks and side effects of the current chemotherapy force us to develop a robust chemotherapeutic system that can deal with off-target hazards and selectively combat cancer growth, invasiveness, and cancer-initiating cells. Here, a pH-responsive cross-linked nanocarrier (140-160 nm) endowed with poly-ß-thioester functionality (CBAPTL) has been sketched and fabricated for noncovalent firm encapsulation of anticancer drug, parthenolide (PTL) at physiological pH (7.4), which enables sustain release of PTL at relevant endosomal pH (∼5.0-5.3). For this, a bolaamphiphilic molecule integrated with ß-thioester and acrylate functionality was synthesized to fabricate the pH-responsive poly-ß-thioester-based cross-linked nanocarrier via Michael addition click reactions in water. The poly-ß-thioester functionality of CBAPTL hydrolyzes at endosomal acidic conditions, thus leading to the selective release of PTL inside the cancer cell. Cross-linked nanocarriers exhibit high serum stability, dilution insensitivity, and targeted cellular uptake at tumor microenvironment (TME), contrasting normal cells. In vitro study using human MCF-7 breast cancer cells demonstrated that CBAPTL exhibited selective cytotoxicity, reduced clonogenic potential, increased reactive oxygen species (ROS) generation, and arrested the progression of the cell cycle at the G0/G1 phase efficiently. CBAPTL induced apoptosis via downregulating pro-proliferative protein Bcl-2 and upregulating proapoptotic proteins p53, BAD, p21, and cleaved PARP-1. CBAPTL inhibited proliferating signaling by suppressing AKT phosphorylation and p38 expression. CBAPTL also blocked the invasion and migration of MCF-7 cells. CBAPTL effectively inhibits primary and secondary mammosphere formation, thereby preventing cancer-initiating cells' growth. Conversely, CBAPTL has negligible effect on human red blood cells (RBCs) and peripheral blood mononuclear cells (PBMCs). These findings highlight the superior efficacy of CBAPTL compared to PTL alone in suppressing cancer cell growth, inducing apoptosis, and preventing invasiveness of MCF-7 cells. Thus, CBAPTL could be considered a possible selective chemotherapeutic cargo against breast cancer without affecting normal cells.

Degradable Polymer-Based Nanoassemblies for Precise Targeting and Drug Delivery to Breast Cancer Cells without Affecting Normal Healthy Cells.

Stimuli-responsive amphiphilic polymers are known to be precursors to forming promising nanoarchitectonics with tunable properties for application in biomedical sciences. Currently, self-immolative polymers are widely recognized as an emerging class of responsive materials with excellent degradability, which is one of the crucial criteria for designing a robust drug delivery vehicle. Here, we design an amphiphilic polyurethane endowed with a redox-responsive self-immolative linker and a pH-responsive tertiary amine on the backbone, which forms entropy-driven nanoscale supramolecular assemblies (average hydrodynamic diameter ∼110 nm) and is programmed to disassemble in a redox environment (GSH) due to the degradation of the polymer in a self-immolative fashion. The nanoassembly shows efficient drug sequestration and release in a controlled manner in response to glutathione (10 mM). The tertiary amine residing on the surface of the nanoassembly becomes protonated in the tumor microenvironment (pH ∼ 6.4-6.8) and generates positively charged nanoassembly (ζ-potential = +36 mV), which enhances the cancer cell-selective cellular uptake. The biological evaluation of the drug-loaded nanoassembly revealed triple-negative breast cancer (MDAMB-231) selective internalization and cell death while shielding normal cells (RBCs or PBMCs) from off-targeting toxicity. We envision that polyurethane with a redox-responsive self-immolative linker might open up new opportunities for a completely degradable polyurethane-based nanocarrier for drug delivery and diagnosis applications.

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.

Prognostic value of circulating mitochondrial DNA in prostate cancer and underlying mechanism.

Circulating DNAs are considered as degraded DNA fragments of approximately 50-200 bp, found in blood plasma, consisting of cell-free mitochondrial and nuclear DNA. Such cell-free DNAs in the blood are found to be altered in different pathological conditions including lupus, heart disease, and malignancies. While nuclear DNAs are being used and being developed as a powerful clinical biomarker in liquid biopsies, mitochondrial DNAs (mtDNAs) are associated with inflammatory conditions including cancer progression. Patients with cancer including prostate cancer are found to have measurable concentrations of mitochondrial DNA in circulation in comparison with healthy controls. The plasma content of mitochondrial DNA is dramatically elevated in both prostate cancer patients and mouse models treated with the chemotherapeutic drug. Cell-free mtDNA, in its oxidized form, induced a pro-inflammatory condition and activates NLRP3-mediated inflammasome formation which causes IL-1ß-mediated activation of growth factors. On the other hand, interacting with TLR9, mtDNAs trigger NF-κB-mediated complement C3a positive feedback paracrine loop and activate pro-proliferating signaling through upregulating AKT, ERK, and Bcl2 in the prostate tumor microenvironment. In this review, we discuss the growing evidence supporting cell-free mitochondrial DNA copy number, size, and mutations in mtDNA genes as potential prognostic biomarkers in different cancers and targetable prostate cancer therapeutic candidates impacting stromal-epithelial interactions essential for chemotherapy response.

Cancer-associated fibroblasts: The chief architect in the tumor microenvironment.

Stromal heterogeneity of tumor microenvironment (TME) plays a crucial role in malignancy and therapeutic resistance. Cancer-associated fibroblasts (CAFs) are one of the major players in tumor stroma. The heterogeneous sources of origin and subsequent impacts of crosstalk with breast cancer cells flaunt serious challenges before current therapies to cure triple-negative breast cancer (TNBC) and other cancers. The positive and reciprocal feedback of CAFs to induce cancer cells dictates their mutual synergy in establishing malignancy. Their substantial role in creating a tumor-promoting niche has reduced the efficacy of several anti-cancer treatments, including radiation, chemotherapy, immunotherapy, and endocrine therapy. Over the years, there has been an emphasis on understanding CAF-induced therapeutic resistance in order to enhance cancer therapy results. CAFs, in the majority of cases, employ crosstalk, stromal management, and other strategies to generate resilience in surrounding tumor cells. This emphasizes the significance of developing novel strategies that target particular tumor-promoting CAF subpopulations, which will improve treatment sensitivity and impede tumor growth. In this review, we discuss the current understanding of the origin and heterogeneity of CAFs, their role in tumor progression, and altering the tumor response to therapeutic agents in breast cancer. In addition, we also discuss the potential and possible approaches for CAF-mediated therapies.

Evaluation of socio-demographic profile and basic risk factors of tuberculosis patients in South 24 Parganas district of West Bengal, India: a hospital-based study.

Aim: To study and analyse the socio-demographic profile and basic risk factors of tuberculosis(TB) patients and their relation with the current epidemiological status of TB registered under the RNTEP program in the study area. Subjects and Methods: This prospective study was conducted on 1743 newly registered tuberculosis patients at TB-DOT center of South 24 Parganas, West Bengal, India from 2011-2014. Socio-demographic variables and baseline characteristics of the participants were noted by a semi-structured questionnaire. Results: Our study results indicate that more than 95% of the TB patients were from lower socioeconomic class, and had poor literacy status and tuberculosis was observed highest in non-agricultural labour and cultivators. Among the young adult's majority of the affected population were females from the lower/upper-lower socioeconomic class. Our analysis revealed that, in successful tuberculosis therapy, men were more defaulters than women. Conclusion: Our study provides a socioeconomic profile and the risk factors of tuberculosis in patients such as the status of therapeutic intervention, involvement of other chronic diseases, age, sex and malnutrition. The findings of this study can be used to plan future studies with specific risk factors of the region and also for implementing the intervention and evaluating its effectiveness.

Multifaceted entrancing role of glucose and its analogue, 2-deoxy-D-glucose in cancer cell proliferation, inflammation, and virus infection.

Chronic exposure to high glucose inside the human body helps in the progression of cancer by activating various signaling pathways including PI3K, Akt, mTOR, Ras, Raf, MAPK, and PKC. Hyperglycemia induces ROS and AGE production and decreases the functional activities of the cellular antioxidant system. By downregulating the prolyl hydroxylase, it stabilizes HIF-α leading to EMT-induced cancer progression and inhibition of apoptosis. High glucose level increases inflammation by creating a pro-inflammatory environment through the production of certain pro-inflammatory mediators (cytokines, chemokines, leukotrienes), and by influencing the recruitment of immune cells, leukocytes in the inflamed region. High glucose impairs the immune response and dysregulates ROS formation through the alteration in ETC and glutaminolysis which makes hyperglycemic patients more susceptible to viral infection. 2-DG is a modified form of D-glucose, that shows anticancer, anti-inflammatory, and anti-viral effects. It enters the cells through GLUT transporters and is converted into 2-deoxy-D-glucose-6-phosphate with the help of hexokinase. It inhibits the glycolysis, the TCA cycle, and the pentose phosphate pathway leading to ATP depletion. By downregulating glucose uptake and energy (ATP) production it halts various pathways responsible for cancer progression. It promotes the formation of anti-inflammatory mediators, and macrophage polarization, and also modulates immune function, which decreases inflammation. 2-DG inhibits PI3K/Akt/mTOR and upregulates the AMPK pathway, causing activation of the SIRT-4 gene that reduces lipogenesis, glucose uptake, nucleotide formation, and alters viral replication thus reducing the chances of infection.

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.

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.

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.

Habitat vulnerability in slum areas of India - What we learnt from COVID-19?

UN-Habitat identified the present COVID-19 pandemic as 'city-centric'. In India, more than 50% of the total cases were documented in megacities and million-plus cities. The slums of cities are the most vulnerable due to its unhygienic environment and high population density that requires an urgent implementation of public healthcare measures. This study aims to examine habitat vulnerability in slum areas to COVID-19 in India using principal component analysis and Fuzzy AHP based technique to develop slum vulnerability index to COVID-19 (SVIcovid-19). Four slum vulnerability groups (i.e. principal components) were retained with eigen-values greater than 1 based on Kaiser criterion - poor slum household status; lack of social distance maintenance; high concentrations of slum population and towns and mobility of the households. This study also mapped composite SVIcovid-19 on the basis of PCA and Fuzzy AHP method at the state level for a better understanding of spatial variations. The result shows that slums located in the eastern and central parts of India (particularly Uttar Pradesh, Bihar, Jharkhand, Odisha, West Bengal) were more vulnerable to COVID-19 transmission due to lack of availability as well as accessibility to the basic services and amenities to slum dwellers. Thus, the findings of the study may not only help to understand the habitat vulnerability in slum areas to COVID-19 but it will also teach a lesson to implement effective policies for enhancing the quality of slum households (HHs) and to reduce the health risk from any infectious disease in future.

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.