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Carbon-based nanostructures with nanometer dimensions have been identified as potential photoluminescence probes for bioimaging due to their biocompatibility, tunable bandgap, and resistance to photobleaching. However, the influence of structural features of carbon quantum dots (CQDs) and graphene quantum dots (GQDs) in bioimaging has not been explored previously. In the present investigation, we elucidated the mechanism of higher PL in GQDs as compared to CQDs as a function of their structural features. TEM and AFM studies revealed that CQDs were spherical (size ~5 nm), while GQDs showed zigzag edges (size ~3 nm). Further, XRD and NMR studies confirmed that CQDs and GQDs show amorphous and crystalline structures with greater sp 2 clusters, respectively. While both the QDs demonstrated multicolor fluorescence against variable excitations with similar lifetime, GQDs showed 7-fold higher QY than CQDs. Bioimaging studies in 2D cell culture, 3D tumoroids, and in vivo suggested a greater intensity of fluorescence in GQDs than CQDs. Additionally, rapid cell internalization was observed in GQDs owing to their positive surface potential by heterogeneous atomic (N and S) doping. Moreover, both CQDs and GQDs have demonstrated better time dependent stability for fluorescence properties. Taken together, the proposed mechanism elucidates the greater PL intensity in GQDs due to quantum confinement effect, crystallinity, and surface edge effects and is a better candidate for bioimaging amongst the carbon family., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Oral cavity squamous cell carcinoma (OCSCC) is the most common malignancy of the oral cavity. The substantial risk factors for OCSCC are the consumption of tobacco products, alcohol, betel quid, areca nut, and genetic alteration. However, technological advancements have occurred in treatment, but the survival decreases with late diagnosis; therefore, new methods are continuously being investigated for treatment. In addition, the rate of secondary tumor formation is 3-7% yearly, which is incomparable to other malignancies and can lead to the disease reoccurrence. Oral cavity cancer (OCC) arises from genetic alterations, and a complete understanding of the molecular mechanism involved in OCC is essential to develop targeted treatments. This review aims to update the researcher on oral cavity cancer, risk factors, genetic alterations, molecular mechanism, classification, diagnostic approaches, and treatment., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

This comprehensive review provides an insight into the pathophysiology, epidemiology, evaluation, and treatment of sickle cell anemia (SCA)-related stroke in developed and developing countries. Vascular injury, hypercoagulability and vaso-occlusion play a role in the pathophysiology of stroke in SCA. Transcranial Doppler ultrasound (TCD) has lowered the incidence of ischemic stroke from 11% to 1% as TCD identifies children who are at risk for stroke, providing opportunities for interventions to reduce this risk. Whereas blood exchange is indicated in acute stroke, chronic transfusions (either simple or exchange on a monthly basis) are used for primary as well as secondary stroke prevention in developed countries. Children with abnormally high TCD velocities (≥ 200 cm/s) are at high risk of stroke and might benefit from hydroxyurea or hydroxycarbamide (HU) after a period of a successful transition from chronic transfusions. Hematopoietic stem cell transplant presents a cure for SCA. Gene therapy is currently investigated and may be offered to patients with SCA who had a stroke or who are at high risk of stroke if proven efficacious and safe. However, gene therapy is not likely to be implemented in low-income countries due to cost. Alternatively, HU is utilized for primary and secondary stroke prevention in developing countries. Further expansion of TCD implementation should be a priority in those settings., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Polymeric micelles are a prevalent topic of research for the past decade, especially concerning their fitting ability to deliver drug and diagnostic agents. This delivery system offers outstanding advantages, such as biocompatibility, high loading efficiency, water-solubility, and good stability in biological fluids, to name a few. The multifunctional polymeric micellar architect offers the added capability to adapt its surface to meet the looked-for clinical needs. This review cross-talks the recent reports, proof-of-concept studies, patents, and clinical trials that utilize polymeric micellar family architectures concerning cancer targeted delivery of anticancer drugs, gene therapeutics, and diagnostic agents. The manuscript also expounds on the underlying opportunities, allied challenges, and ways to resolve their bench-to-bedside translation for allied clinical applications., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Recent findings suggest that the cellular and extracellular materials surrounding the cancerous cells from an atypical tumor microenvironment (TM) play a pivotal role in the process of tumor initiation and progression. TM comprises an intricate system involving diverse cell types including endothelial cells, pericytes, smooth muscle cells, fibroblasts, various inflammatory cells, dendritic cells, and cancer stem cells (CSCs). The TM-forming cells dynamically interact with the cancerous cells through various signaling mechanisms and pathways. The existence of this dynamic cellular communication is responsible for creating an environment suitable for sustaining a reasonably high cellular proliferation. Presently, researchers are showing interest to use these TM conditions to mediate effective targeting measures for cancer therapy. The use of nanotherapeutics-based combination therapy; stimuli-responsive nanotherapeutics targeting acidic pH, hypoxic environment; and nanoparticle-induced hyperthermia are some of the approaches that are under intense investigation for cancer therapy. This review discusses TM and its role in cancer progression and crosstalk understanding, opportunities, and epigenetic modifications involved therein to materialize the capability of nanotherapeutics to target cancer by availing TM. STATEMENT OF SIGNIFICANCE: This article presents various recent reports, proof-of-concept studies, patents, and clinical trials on the concept of tumor microenvironment for mediating the cancer-specific delivery of nanotechnology-based systems bearing anticancer drug and diagnostics. We highlight the potential of tumor microenvironment; its role in disease progression, opportunities, challenges, and allied treatment strategies for effective cancer therapy by conceptual understanding of tumor microenvironment and epigenetic modifications involved. Specifically, nanoparticle-based approaches to target various processes related to tumor microenvironment (pH responsive, hypoxic environment responsive, targeting of specific cells involved in tumor microenvironment, etc.) are dealt in detail., (Copyright © 2019 Acta Materialia Inc. Published by Elsevier Ltd. All rights reserved.)

Stroke is the second largest disease of mortality. The biggest hurdle in designing effective brain drug delivery systems is offered by the blood-brain barrier (BBB), which is highly impermeable to many drugs. Albumin nanoparticles (NP) have gained attention due to their multiple ligand binding sites and long circulatory half-life. Citicoline (CIT) is reported to enhance the acetylcholine secretion in the brain and also helps in membrane repair and regeneration. However, the poor BBB permeation of CIT results in lower levels of CIT in the brain. This demands the development of a suitable delivery platform to completely realize the therapeutic benefit of CIT in stroke therapy. This investigation reports the synthesis and characterization of second generation (2.0 G) dendrimer Amplified Albumin (dAA) biopolymer by FTIR, MALDI-TOF, and surface charge (mV). Further, the synthesized biopolymer has been utilized to develop a CIT nanoformulation using a commercially translatable one-pot process. Release of CIT from biopolymer was performed within an acetate buffer at pH 5 and Phosphate buffer at pH 7.4. Further, we investigated the ability of biopolymer to permeate BBB by in vitro permeability assay in bEnd.3 cells. MTT assay of CIT-dAA-NP, CIT-ANP, and 2.0 G PAMAM dendrimers was performed in bEnd.3 cells. Therapeutic efficacy of the synthesized biopolymer was determined by VEGF gene expression within an in vitro hypoxia model in PC12 cells. Thus, this investigation resulted in biopolymers that can be used to deliver any therapeutic agent by altering the permeability of the BBB. Also, cationization by dendrimer grafting is one such strategy that may be used to cationize any other negatively charged polymer, such as albumin. The synthesized biopolymer is not limited to deliver molecules to the brain, but can also be used to increase the loading of negatively-charged drug molecules, siRNA, or any other oligonucleotide., (Copyright © 2019 Elsevier B.V. All rights reserved.)

In tumorous tissues, the absence of vasculature supportive tissues intimates the formation of leaky vessels and pores (100 nm to 2 μm in diameter) and the poor lymphatic system offers great opportunity to treat cancer and the phenomenon is known as Enhanced permeability and retention (EPR) effect. The trends in treating cancer by making use of EPR effect is increasing day by day and generate multitudes of possibility to design novel anticancer therapeutics. This review aimed to present various factors affecting the EPR effect along with important things to know about EPR effect such as tumor perfusion, lymphatic function, interstitial penetration, vascular permeability, nanoparticle retention etc. This manuscript expounds the current advances and cross-talks the developments made in the of EPR effect-based therapeutics in cancer therapy along with a transactional view of its current clinical and industrial aspects., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Breast cancer, a death-dealing disease mainly affects the women populace in the world. Outmoded remedial treatments like chemo and radiotherapy against breast cancer have manifold limitations like systemic and local toxicity resulting in the failure of treatment and cancer relapse. Recurrence and treatment failure is due to the presence of the minor number of cells in the tumor called cancer stem cells (CSCs) stocked with the properties like epithelial-mesenchymal transition, drug resistibility, auto self-renewability, and stemness. But, the stemness in these cells is different from the normal stem cells with regards to their self-renewal signaling pathways which gets dysregulated due to genomic and epigenome changes. In the earlier period's headway in the cancer research led to the advancement of new targets by understanding the pathophysiological mechanism behind cancer progression but still, the mortality rate i. the breast cancer is at its peak due to their unclear understanding of the stemness signaling regulations. The present review highlights the current clinical limitations in treating cancer stem cells and discusses the recent writings of their stemness signaling regulations required in maintenance of self-renewal capability and metastasis. More importantly, it further describes the present clinical and preclinical updates targeting cancer stem cells pathways. A strong consideration of these signalings and developing the treatment strategies with the existed chemotherapy may possibly offer a promising approach to eradicate cancer stem cells for improving the cancer survival rate to persuade a long-term clinical response., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Aim: Stroke is devastating with a limited choice of intervention. Many pharmacological entities are available but none of them have evolved successfully in counteracting the multifaceted molecular alterations following stroke. Myeloperoxidase (MPO) has been reported to play an important role in neuroinflammation following neurodegenerative diseases. Therefore, using it as a therapeutic target may be a strategy to confer neuroprotection in stroke. Trigonelline (TG), a plant alkaloid has shown neuroprotective effects in the past. Here we explore its neuroprotective effects and its role in glutathione mediated MPO inhibition in ischemic stroke., Methods: An in silico study was performed to confirm effective TG and MPO interaction. An in vitro evaluation of toxicity with biochemical estimations was performed. Further, in vivo studies were undertaken where rats were treated with 25, 50 and 100 mg/kg TG or standard MPO inhibiting drug4‑Aminobenzoic hydrazide (4‑ABH) at 60 min prior, post immediate and an hour post 90 min of middle cerebral artery occlusion (MCAo) followed by 24 h reperfusion. Rats were evaluated for neurodeficit and motor function tests. Brains were further harvested for infarct size evaluation, biochemical analysis, and western blot experiments., Key Findings: TG at 100 mg/kg dose i.p. administered immediately post ischemia confers neuroprotection by reducing cerebral infarct with improvement in motor and neurodeficit scores. Furthermore, elevated nitrite and MDA levels were also found to be reduced in brain regions in the treated group. TG also potentiated intrinsic antioxidant status and markedly inhibited reduced glutathione mediated myeloperoxidase expression in the cortical brain region., Significance: TG confers neuroprotection by reduced glutathione mediated myeloperoxidase inhibition in ischemic stroke., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Objective: The phosphatidylinositol 3-kinase (PIK3) genes, which code for heterodimeric lipid kinases, consist of a catalytic subunit, p110α (PIK3CA), which regulates cell proliferation, apoptosis, and metastasis. Recently, a high frequency of somatic mutations was observed in the PIK3CA gene in various cancer types, including oral squamous cell carcinoma (OSCC). This study aimed to determine the frequency of oncogenic hotspot mutations in exons 9 and 20 of the PIK3CA gene and its correlation with the clinical characteristics of OSCC patients in an Indian population., Study Design: We analyzed exons 9 and 20 of the PIK3CA gene using polymerase chain reaction (PCR) and direct genomic sequencing of 50 OSCC primary tumors., Results: We observed two hotspot oncogenic mutations (E542 K, E545 K) in exon 9 and two synonymous mutations (A994 A, T1025 T) in exon 20. Moreover, we identified two single nucleotide polymorphisms (SNPs), rs114587137 (C>T) and rs17849071 (T>G), in intron 9 of the PIK3CA gene. Both oncogenic hotspot mutations were reported primarily in patients with advanced-stage cancer of the buccal mucosa., Conclusions: We have observed a 4% oncogenic mutation frequency of the PIK3CA gene, which plays a minor role in the development of OSCC in an Indian population., (Copyright © 2015 Elsevier Inc. All rights reserved.)

Arsenic hypertolerant bacterial cells were isolated from the common industrial effluent treatment plant, Vapi, India. Strain DJ-1 sustaining 400 mM, As (V) out of 16 bacterial strains was identified as Bacillus sp. strain DJ-1 through 16S rRNA ribotyping. The maximum arsenic accumulation of 9.8+/-0.5 mg g(-1) (dry weight) was observed during stationary phase of growth. Intracellular compartmentalization has shown 80% of arsenic accumulation in cytoplasm. The lack of arsC gene and arsenate reductase activity indicated that Bacillus sp. strain DJ-1 may lack classical ars operon and detoxification may be mediated through some novel mechanism. The arsenite binding protein was purified by affinity chromatography and characterized as DNA protection during starvation (DPS) protein by electrospray ionization mass spectrometry. The induction of DPS showed the adaptation of bacteria in arsenic stress condition and/or in detoxification mechanism, relies on its ability to bind with arsenic. These results indicate the hypertolerance with higher intracellular accumulation of arsenic by Bacillus sp. strain DJ-1, which could be mediated by DPS protein thus signifying this organism is a potential candidate for the removal of arsenic from industrial wastewater, which needs further study.

Background: Diabetic nephropathy is a relatively common microvascular complication in people suffering from diabetic mellitus. Chronic hyperglycemia leads to the accumulation of advanced glycosylation end products (AGEs) that covalently trap extravasated serum proteins such as immunoglobulins, albumin, and LDL through glucose derived cross-linking to the extra vascular matrix., Methods: Serum fructosamine, glycosylated hemoglobin and percent glycosylation of IgG, IgA, IgM were measured in five different groups of human subjects: 50 normal individuals; 40 type 2 DM patients; 42 type 1 DM patients; 40 type 2 DM patients with nephropathy and 37 type 1 DM patients with nephropathy., Results: Patients with long-term history of diabetes and chronic hyperglycemia as well as suffering from diabetic nephropathy showed an increased glycosylated hemoglobin level and serum fructosamine as compared to those with diabetes mellitus and to the normal individuals. Glycosylation of IgG, IgA and IgM showed an increase in both type 1 and type 2 DM patients with nephropathy as compared to the diabetic patients without any complication. A positive correlation has been observed between glycosylated IgG and glycosylated hemoglobin (R2=0.522, 0.5113, 0.7117, 0.673) in type 1 and type 2 DM without and with diabetic nephropathy, respectively, whereas correlation between glycosylated IgG and serum fructosamine was observed only in type 1 and type 2 DM without nephropathy (R2=0.7318, 0.5767)., Conclusion: The present study suggests that glycosylation of IgG is an equivalent marker for advanced glycosylation as GHb and may have some role to play in the on onset of diabetic nephropathy by altering their immunoreactivity leading to microvascular complications.