2D nanostructures: Potential in diagnosis and treatment of Alzheimer's disease.

Two-dimensional (2D) nanomaterials have garnered enormous attention seemingly due to their unusual architecture and properties. Graphene and graphene oxide based 2D nanomaterials remained the most sought after for several years but the quest to design superior 2D nanomaterials which can find wider application gave rise to development of non-graphene 2D materials as well. Consequently, in addition to graphene based 2D nanomaterials, 2D nanostructures designed using macromolecules (such as DNAs, proteins, peptides and peptoids), transition metal dichalcogenides, transition-metal carbides and/or nitrides (MXene), black phosphorous, chitosan, hexagonal boron nitrides, and graphitic carbon nitride, and covalent organic frameworks have been developed. Interestingly, these 2D nanomaterials have found applications in diagnosis and treatment of various diseases including Alzheimer's disease (AD). Although AD is one of the most debilitating neurodegenerative conditions across the globe; unfortunately, there remains a paucity of effective diagnostic and/or therapeutic intervention for it till date. In this scenario, nanomaterial-based biosensors, or therapeutics especially 2D nanostructures are emerging to be promising in this regard. This review summarizes the diagnostic and therapeutic platforms developed for AD using 2D nanostructures. Collectively, it is worth mentioning that these 2D nanomaterials would seemingly provide an alternative and intriguing platform for biomedical interventions.

Reviewing the Prospective Pharmacological Potential of Isothiocyanates in Fight against Female-Specific Cancers.

Gynecological cancers are the most commonly diagnosed malignancies in females worldwide. Despite the advancement of diagnostic tools as well as the availability of various therapeutic interventions, the incidence and mortality of female-specific cancers is still a life-threatening issue, prevailing as one of the major health problems worldwide. Lately, alternative medicines have garnered immense attention as a therapeutic intervention against various types of cancers, seemingly because of their safety profiles and enhanced effectiveness. Isothiocyanates (ITCs), specifically sulforaphane, benzyl isothiocyanate, and phenethyl isothiocyanate, have shown an intriguing potential to actively contribute to cancer cell growth inhibition, apoptosis induction, epigenetic alterations, and modulation of autophagy and cancer stem cells in female-specific cancers. Additionally, it has been shown that ITCs plausibly enhance the chemo-sensitization of many chemotherapeutic drugs. To this end, evidence has shown enhanced efficacy in combinatorial regimens with conventional chemotherapeutic drugs and/or other phytochemicals. Reckoning with these, herein, we discuss the advances in the knowledge regarding the aspects highlighting the molecular intricacies of ITCs in female-specific cancers. In addition, we have also argued regarding the potential of ITCs either as solitary treatment or in a combinatorial therapeutic regimen for the prevention and/or treatment of female-specific cancers. Hopefully, this review will open new horizons for consideration of ITCs in therapeutic interventions that would undoubtedly improve the prognosis of the female-specific cancer clientele. Considering all these, it is reasonable to state that a better understanding of these molecular intricacies will plausibly provide a facile opportunity for treating these female-specific cancers.

Phenethyl Isothiocyanate Induces Apoptosis Through ROS Generation and Caspase-3 Activation in Cervical Cancer Cells.

The latest research shows that current chemotherapeutics are ineffective because of the development of resistance in cervical cancer cells, and hence, their scope of use is limited. The main concern of researchers at the moment is the discovery of safe and effective antiproliferative plant chemicals that can aid in the battle against cervical cancer. Previous studies have shown the possible anticancer potential of phenethyl isothiocyanate obtained from cruciferous plants for many cancers, which targets various signaling pathways to exercise chemopreventive and therapeutic effects. This provides the basis for studying phenethyl isothiocyanate's therapeutic potential against cervical cancer. In the present study, cervical cancer cells were treated with various doses of phenethyl isothiocyanate, alone and in combination with cisplatin. Phenethyl isothiocyanate alone was sufficient to cause nucleus condensation and fragmentation and induce apoptosis in cervical cancer cells, but evident synergistic effects were observed in combination with cisplatin. In addition, phenethyl isothiocyanate treatment increased the production of intracellular ROS in a dose-dependent manner in cervical cancer cells. Furthermore, investigation of phenethyl isothiocyanate induced mitochondrial reactive oxygen species production, and activation of caspases showed that phenethyl isothiocyanate significantly activated caspase-3.

Recent Nano-based Therapeutic Intervention of Bioactive Sesquiterpenes: Prospects in Cancer Therapeutics.

In the recent scenario, nanotechnology-based therapeutics intervention has gained tremendous impetus all across the globe. Nano-based pharmacological intervention of various bioactive compounds has been explored on an increasing scale. Sesquiterpenes are major constituents of essential oils (EOs) present in various plant species which possess intriguing therapeutic potentials. However, owing to their poor physicochemical properties; they have pharmacological limitations. Recent advances in nano-based therapeutic interventions offer various avenues to improve their therapeutic applicability. Reckoning with these, the present review collates various nano-based therapeutic intervention of sesquiterpenes with prospective potential against various debilitating diseases especially cancer. In our viewpoint, considering the burgeoning advancement in the field of nanomedicine; in the near future, the clinical applicability of these nano-formulated sesquiterpenes can be foreseen with great enthusiasm.

Ovalbumin self-assembles into amyloid nanosheets that elicit immune responses and facilitate sustained drug release.

Amyloids are associated with many neurodegenerative diseases, motivating investigations into their structure and function. Although not linked to a specific disease, albumins have been reported to form many structural aggregates. We were interested in investigating host immune responses to amyloid fibrils assembled from the model protein ovalbumin. Surprisingly, upon subjecting ovalbumin to standard denaturing conditions, we encountered giant protein nanosheets harboring amyloid-like features and hypothesized that these nanosheets might have potential in clinical or therapeutic applications. We found that the nanosheets, without the administration of any additional adjuvant, evoked a strong antibody response in mice that was higher than that observed for native ovalbumin. This suggests that amyloid nanosheets have a self-adjuvanting property. The nanosheet-induced immune response was helper T cell 2 (Th2) biased and negligibly inflammatory. While testing whether the nanosheets might form depots for the sustained release of precursor proteins, we did observe release of ovalbumin that mimicked the conformation of native protein. Moreover, the nanosheets could load the anticancer drug doxorubicin and release it in a slow and sustained manner. Taken together, our results suggest that amyloid nanosheets should be further investigated as either an antigen delivery vehicle or a multifunctional antigen and drug co-delivery system, with potential applications in simultaneous immunotherapy and chemotherapy.

The skin microbiome and immune system: Potential target for chemoprevention?

There has been increasing interest in understanding the role of the human microbiome in skin diseases. Microbiome studies are being utilized in skin cancer research in numerous ways. Commensal bacteria are being studied as a potential tool to judge the biggest environmental risk of skin cancer, ultraviolet (UV) radiation. Owing to the recognized link of skin microbes in the process of inflammation, there have been theories linking commensal bacteria to skin cancer. Viral metagenomics has also provided insight into virus linked forms of skin cancers. Speculations can be drawn for skin microbiome that in a manner similar to gut microbiome, they can be involved in chemoprevention of skin cancer. Nonetheless, there are definitely huge gaps in our knowledge of the relationship of microbiome and skin cancers, especially in relation to chemoprevention. The utilization of microbiome in skin cancer research seems to be a promising field and may help yield novel skin cancer prevention and treatment options. This review focuses on recent utilization of the microbiome in skin cancer research, and it explores the potential of utilizing the microbiome in prevention, earlier diagnosis, and treatment of skin cancers.

Gold Nanoparticle-Photosensitizer Conjugate Based Photodynamic Inactivation of Biofilm Producing Cells: Potential for Treatment of C. albicans Infection in BALB/c Mice.

BACKGROUND: Photodynamic therapy (PDT) has been found to be effective in inhibiting biofilm producing organisms. We investigated the photodynamic effect of gold nanoparticle (GNP) conjugated photosensitizers against Candida albicans biofilm. We also examined the photodynamic efficacy of photosensitizer (PS) conjugated GNPs (GNP-PS) to treat skin and oral C. albicans infection in BALB/c mice. METHODS: The biomimetically synthesized GNPs were conjugated to photosensitizers viz. methylene blue (MB) or toluidine blue O (TB). The conjugation of PSs with GNPs was characterized by spectroscopic and microscopic techniques. The efficacy of gold nanoparticle conjugates against C. albicans biofilm was demonstrated by XTT assay and microscopic studies. The therapeutic efficacy of the combination of the GNP conjugates against cutaneous C. albicans infection was examined in mouse model by enumerating residual fungal burden and histopathological studies. RESULTS: The GNP-PS conjugate based PDT was found to effectively kill both C. albicans planktonic cells and biofilm populating hyphal forms. The mixture of GNPs conjugated to two different PSs significantly depleted the hyphal C. albicans burden against superficial skin and oral C. albicans infection in mice. CONCLUSION: The GNP-PS conjugate combination exhibits synergism in photodynamic inactivation of C. albicans. The GNP conjugate based PDT can be employed effectively in treatment of cutaneous C. albicans infections in model animals. The antibiofilm potential of PDT therapy can also be exploited in depletion of C. albicans on medical appliances such as implants and catheters etc.

Amyloid form of ovalbumin evokes native antigen-specific immune response in the host: prospective immuno-prophylactic potential.

Amyloids are highly organized protein aggregates that arise from inappropriately folded versions of proteins or polypeptides under both physiological as well as simulated ambiences. Once thought to be irreversible assemblies, amyloids have begun to expose their more dynamic and reversible attributes depending upon the intrinsic properties of the precursor protein/peptide and experimental conditions such as temperature, pressure, structural modifications in proteins, or presence of chemicals in the reaction mixture. It has been repeatedly proposed that amyloids undergo transformation to the bioactive peptide/protein forms under specific conditions. In the present study, amyloids assembled from the model protein ovalbumin (OVA) were found to release the precursor protein in a slow and steady manner over an extended time period. Interestingly, the released OVA from amyloid depot was found to exhibit biophysical characteristics of native protein and reacted with native-OVA specific monoclonal as well as polyclonal antibodies. Moreover, antibodies generated upon immunization of OVA amyloidal aggregates or fibrils were found to recognize the native form of OVA. The study suggests that amyloids may act as depots for the native form of the protein and therefore can be exploited as vaccine candidates, where slow antigen release over extended time periods is a pre-requisite for the development of desired immune response.

An alternative chemical redox method for the production of bispecific antibodies: implication in rapid detection of food borne pathogens.

Bi-functional antibodies with the ability to bind two unrelated epitopes have remarkable potential in diagnostic and bio-sensing applications. In the present study, bispecific antibodies that recognize human red blood cell (RBC) and the food borne pathogen Listeria monocytogenes (L. monocytogenes) were engineered. The procedure involves initial reduction of a mixture of anti-RBC and anti-Listeria antibodies followed by gradual re-oxidation of the reduced disulphides. This facilitates association of the separated antibody chains and formation of hybrid immunoglobulins with affinity for the L. monocytogenes and human RBC. The bispecific antibodies caused the agglutination of the RBCs only in the presence of L. monocytogenes cells. The agglutination process necessitated the specific presence of L. monocytogenes and the red colored clumps formed were readily visible with naked eyes. The RBC agglutination assay described here provides a remarkably simple approach for the rapid and highly specific screening of various pathogens in their biological niches.

Illuminating the petite picture of T cell memory responses to Listeria monocytogenes.

The ease to culture, moderately less safety constraints in handling, and above all, hurdle free induction of an anticipated infection in mouse rendered Listeria monocytogenes the rank of a model organism for studying a variety of host immune responses. Listeria monocytogenes being an intracellular pathogen evokes potent CD8 T cell response during which CD8 T cells pass through a massive expansion phase. This is generally followed by contraction phase wherein majority of activated cells undergo apoptosis leaving behind a population of memory CD8 T cells that has potential to confer enhanced protection upon reencounter with the same pathogen. Functional attributes of various cytokines, transcription factors, receptors, adaptors, and effectors pertaining to the generation of robust memory T cell response have begun to be unravelled for better understanding of memory and opening avenues to create superior vaccine strategies. This review is an attempt to unveil related discoveries along with updating recent advances on this issue.

Tissue specific heterogeneity in effector immune cell response.

Post pathogen invasion, migration of effector T-cell subsets to specific tissue locations is of prime importance for generation of robust immune response. Effector T cells are imprinted with distinct "homing codes" (adhesion molecules and chemokine receptors) during activation which regulate their targeted trafficking to specific tissues. Internal cues in the lymph node microenvironment along with external stimuli from food (vitamin A) and sunlight (vitamin D3) prime dendritic cells, imprinting them to play centre stage in the induction of tissue tropism in effector T cells. B cells as well, in a manner similar to effector T cells, exhibit tissue-tropic migration. In this review, we have focused on the factors regulating the generation and migration of effector T cells to various tissues along with giving an overview of tissue tropism in B cells.

Ether lipid vesicle-based antigens impart protection against experimental listeriosis.

BACKGROUND: Incidence of food-borne infections from Listeria monocytogenes, a parasite that has adapted intracellular residence to avoid antibody onslaught, has increased dramatically in the past few years. The apparent lack of an effective vaccine that is capable of evoking the desired cytotoxic T cell response to obliterate this intracellular pathogen has encouraged the investigation of alternate prophylactic strategies. It should also be noted that Archaebacteria (Archae) lipid-based adjuvants enhance the efficacy of subunit vaccines. In the present study, the adjuvant properties of archaeosomes (liposomes prepared from total polar lipids of archaebacteria, Halobacterium salinarum) combined with immunogenic culture supernatant antigens of L. monocytogenes have been exploited in designing a vaccine candidate against experimental listeriosis in murine model. METHODS: Archaeosome-entrapped secretory protein antigens (SAgs) of L. monocytogenes were evaluated for their immunological responses and tendency to deplete bacterial burden in BALB/c mice challenged with sublethal listerial infection. Various immunological studies involving cytokine profiling, lymphocyte proliferation assay, detection of various surface markers (by flowcytometric analysis), and antibody isotypes (by enzyme-linked immunosorbent assay) were used for establishing the vaccine potential of archaeosome-entrapped secretory proteins. RESULTS: Immunization schedule involving archaeosome-encapsulated SAgs resulted in upregulation of Th1 cytokine production along with boosted memory in BALB/c mice. It also showed protective effect by reducing listerial burden in various vital organs (liver and spleen) of the infected mice. However, the soluble form of the antigens (SAgs) and their physical mixture with sham (empty) archaeosomes, besides showing feeble Th1 response, were unable to protect the animals against virulent listerial infection. CONCLUSION: On the basis of the evidence provided by the current data, it is inferred that archaeosome-entrapped SAgs formulation not only enhances cytotoxic T cell response but also helps in the clearance of pathogens and thereby increases the survival of the immunized animals.

Fungus-mediated biological synthesis of gold nanoparticles: potential in detection of liver cancer.

BACKGROUND: Nanomaterials are considered to be the pre-eminent component of the rapidly advancing field of nanotechnology. However, developments in the biologically inspired synthesis of nanoparticles are still in their infancy and consequently attracting the attention of material scientists throughout the world. Keeping in mind the fact that microorganism-assisted synthesis of nanoparticles is a safe and economically viable prospect, in the current study we report Candida albicans-mediated biological synthesis of gold nanoparticles. METHODS AND RESULTS: Transmission electron microscopy, atomic force microscopy, and various spectrophotometric analyses were performed to characterize the gold nanoparticles. The morphology of the synthesized gold particles depended on the abundance of C. albicans cytosolic extract. Transmission electron microscopy, nanophox particle analysis, and atomic force microscopy revealed the size of spherical gold nanoparticles to be in the range of 20-40 nm and nonspherical gold particles were found to be 60-80 nm. We also evaluated the potential of biogenic gold nanoparticles to probe liver cancer cells by conjugating them with liver cancer cell surface-specific antibodies. The antibody-conjugated gold particles were found to bind specifically to the surface antigens of the cancer cells. CONCLUSION: The antibody-conjugated gold particles synthesized in this study could successfully differentiate normal cell populations from cancerous cells.

Synthesis and characterization of novel PUFA esters exhibiting potential anticancer activities: an in vitro study.

Polyunsaturated fatty acids (PUFAs) have been reported to play a regulatory role in tumour growth progression. In the present study, we have synthesized ester derivatives of two important PUFA viz., linoleic acid (LA) and arachidonic acid (AA) with propofol, a widely used general anaesthetic-sedative agent. The novel propofol ester analogues have been found to inhibit various cancer cell lines in a dose-dependent manner. Moreover, the compounds have been found to induce apoptotic cell death by enhancing the release of cytochrome c and expression of caspase-3. The data of the present study suggest that novel propofol-PUFA esters have strong potential to emerge as effective anticancer agents.