Objective:During inflammation and oxidative stress, vascular endothelial cell surfaces express high levels of adhesion molecules such as intercellular adhesion molecule 1 (ICAM1) which bind the circulatory leukocytes (e.g. macrophages), through counter receptors LFA/Mac1. The bound leukocytes on sub-endothelial translocation accumulate oxidized lipids and proteins, developing atherosclerotic plaques by foam cell and fatty streak formations. Herewith, nordihydroguaiaretic acid (NDGA) prevails as a polyphenol in the Larrea tridentate plant, with potent antioxidant and anti-inflammatory traits. This study for the first time elucidates that NDGA attenuates TNFα-dependent ICAM1 expression in the cultured human umbilical vein endothelial cells (HUVECs), by targeting the TNFα-PI3K-NF-κB-ICAM1 pathway. Materials and Methods:Cultured HUVECs were treated with pro-inflammatory and pro-oxidative cytokine TNFα, to induce ICAM1 mRNA level and protein expression on HUVECs cell surface as documented by northern and western blot, respectively. The effect of varying NDGA concentrations was examined on TNFα-stimulated ICAM1 expression and monocyte attachment assay. Results:Pre-TNFα-NDGA treatment of HUVECs moderated TNFα-dependent ICAM1 expression and monocyte attachment on vascular endothelium by inhibiting the PI3K-NF-κB-ICAM1 signaling pathway. Conclusion:In this study, the NDGA anti-inflammatory and anti-adhesion essence is elucidated via impaired cytoplasm to nucleus translocation of pro-oxidative and pro-inflammatory transcription factor NF-κB, moderating the ICAM1 expression and monocyte attachment.
Introduction: Triple-negative breast cancers (TNBCs) are a type of breast cancer (BC) characterized by the absence of ER, PR, and HER2 expression. They account for 10-15% of invasive BC cases and are known for being aggressive and highly metastatic. TNBC patients face limited effective treatment options due to the inherent heterogeneity of the disease and a lack of targetable receptor molecules. Methods: Chemotherapy, used as part of neoadjuvant or adjuvant therapy, remains the major treatment recourse but is associated with toxicity, resistance, and relapse. Unlike other BCs, TNBCs' tumor microenvironment (TME) features many tumor-associated antigens (TAAs) and significant lymphocyte infiltration, such as Tc cells and other immune cells, e.g., NK cells. The collection of relevant studies herein was done by typing the keywords “Targeted Immunotherapy for Triple Negative Breast Cancer” on Google and PubMed databases, which were henceforth retrieved with a focus on recent attempts. Results: TNBCs are considered immunologically "hot". However, the presence of significant immunosuppressive cells, including Tregs, TAMs, and MDSCs, along with inhibitory cytokines, such as IL- 10 secreted by these cells, expression of immunosuppressive molecules, such as PD-1, PD-L1, and CTLA-4, weakens the anti-tumor response through immunosuppressive actions. Discussion: TNBC-TME is a target for immunotherapy. Current immunotherapeutic strategies target the TNBC TME using immune checkpoint inhibitors (ICIs) against PD-1, PD-L1, and CTLA-4. Additionally, several studies focus on developing vaccines targeting immunosuppressive cells and molecules of the TNBC TME. Conclusion: This review highlights advancements in immunotherapy strategies for mitigating TNBC, with a particular focus on targeting immunosuppressive molecules.
Background: The human body’s exposure to high levels of endogenous estrogens and their metabolites, such as estradiol, estriol, 2-hydroxyestradiol, and 4-hydroxyestradiol, is implicated in the development and complications of breast cancers (BCs). Besides endogenous estrogen production, the human body is also exposed to environmental sources of estrogen and estrogen-like compounds, which include pharmaceutical estrogens, xenoestrogens, and phytoestrogens. Females consume pharmaceutical estrogens as a constituent of postmenopausal hormone replacement therapy (HRT) and oral contraceptive pills, either alone or in combination with progestins. Additionally, humans, including females, are exposed to estrogen-resembling non-native compounds called xenoestrogens, prevailing in pesticides, plastics, and personal care items via inhalation, dermal contact, and oral consumption. Several phytoestrogens, such as isoflavones and lignans, are consumed by humans as food ingredients. Methods and Results: Emerging cellular and molecular experimental evidence indicates that when binding to estrogen receptors (ERs), various pharmaceutical estrogens, including equine/synthetic forms, progestin combinations, and xenoestrogens, promote BC development and complications by triggering survival, proliferation, angiogenesis, and invasion of these cells. Conversely, other experimental observations reveal the protective and beneficial effects of phytoestrogens like genistein from soy products on BC development and complications. Conclusions: This comprehensive review article describes the implications of exposure to exogenous estrogens, such as pharmaceutical estrogens, xenoestrogens, and phytoestrogens, as risk factors in the prevention or development of BC and its complications.
The natural essence, biocompatibility, and pleiotropic functioning of plant polyphenols have swiftly emerged as integrated assets for biomedical and environmental applications of plant resources capped ZnO NPs. Simultaneous reducing cum capping abilities, synergistic edible prospects, and precursor-plant extract stoichiometry-driven robust size-shape modulation are the major encouragements being explored for increasing recent interest in biomedical-environmental applications of plant extracts (PEs) capped ZnO NPs. The structure-function dynamics of extracts from leaves, roots, fruits, seeds, and whole plants sum up the multifaceted applications of polyphenols-capped ZnO NPs. Recent interest in plant resources' biomedical and environmental utility capped ZnO NPs mandates discussing the correlative mechanisms for sustainable future insights. PEs capped ZnO NPs as drug carriers and sensing agents significantly moderate the toxic chemotherapeutic drug intake via enhanced tumor cell internalization, aided by synergistic immune-modulating actions of constituent phytochemicals. On the environmental front, integrated antioxidant features of plant resources and ZnO NPs make them potent degrading agents for the sustainable degradation of persisting effluents. Keeping the above aspects in mind, this review article focuses on the correlative mechanisms underlying the biomedical and environmental remediation applications of plant resources made ZnO NPs. This article would augment the awareness of ZnO NPs multifaceted applications for consolidating the understanding of predictive mechanistic controls.
The transmembrane protein receptor for advanced glycation end products (mRAGEs) is recognized as an immunoglobulin class of molecule. Mammalian cells produce a carboxy terminus truncated version of RAGE, either as endogenous soluble RAGE (esRAGE) or soluble RAGE (sRAGE), both being generated via proteolytic cleavage or alternative mRAGE-mRNA splicing. Through its extracellular domains (V, C1, and C2), RAGE interacts with seemingly unrelated ligands such as advanced glycation end products (AGEs), high mobility group box protein 1 (HMGB1), S100/calgranulin family, lysophosphatidic acid (LPA), oligomeric forms of amyloid beta peptide (Aβ-peptide), islet amyloid polypeptide (IAPP), attributing to the recognition as multi-ligand receptor. Under physiological conditions, lung tissues exhibit abundant RAGE expression compared to others, being involved in the development, spread, and homeostatic regulation, the prominent of which are lung alveolar type 1 (AT-1) epithelial cells. However, in pathophysiological conditions, supraphysiological expression of RAGE and its ligands and subsequent receptor-ligand interactions result in the aggravation of oxidative stress and inflammation, causing the propagation of various non-communicable disease conditions. The physiological RAGE expression may protect against non-small cell lung cancers (NSCLCs), as suppressed RAGE expression in lung tissues may complicate NSCLCs. The protective role of RAGE in lung tissues is surprisingly contrary to its activities in other cancers, which are unanimously characterized by its enhanced expression-driven propagation of the conditions. Anti-RAGE molecules including esRAGE/sRAGE attenuate RAGEdependent multiple diseased conditions.
Glycobiology aims at structure-function correlational analysis of carbohydrates (sugar or glycan). A monosaccharide is the simplest form of carbohydrate that no longer be hydrolyzed. The other forms of carbohydrates are formed by glycosidic linkages of monosaccharides, such as disaccharides, oligosaccharides, and polysaccharides, comprising two, three to ten, and more than ten monosaccharides, respectively. Carbohydrates act as one of the major energy sources (e.g., ATP) and are also involved in cellular protection, stabilization, organization, and barrier functions. In the cellular system, carbohydrates are present in pure and proteinconjugated forms, which are referred to as glycoproteins. Conjugated carbohydrates are also present in the form of glycolipids and proteoglycans. Notably, N- and O-linked glycosylation as major forms occur in the rough surface endoplasmic reticulum (RER) and Golgi apparatus respectively, adding carbohydrates to proteins and thus making glycoproteins. Relatively fewer common types of glycosylation are the C-linked glycosylation, S-linked glycosylation, glypiation, and phosphoglycosylation. A complex interplay of two enzyme groups such as glycosyl transferases (adding carbohydrates to proteins) and glycosidases/glycosyl hydrolases (removing carbohydrates from proteins) control the glycosylation extent. Prominent cellular factors regulating glycosylation are the availability of carbohydrates, proteins, enzymes, movement of proteins from RER to Golgi, and several other environmental factors regulating post-translational modifications. This chapter describes the various aspects of glycobiology including protein glycosylation, purification, and analysis of glycans, and their role in physiology and pathophysiology.
The Receptor for Advanced Glycation End Products (RAGE) has emerged as a pivotal player in the pathogenesis of cardiovascular and diabetic complications. An in-depth exploration of RAGE involvement in the disease processes, elucidating the molecular mechanisms, signaling pathways, and the associated pathological outcomes, is discussed. In diabetes, chronic hyperglycemia leads to the formation and accumulation of advanced glycation end products (AGEs), which activate RAGE and subsequently initiate a cascade of pro-inflammatory and pro-oxidative events. These processes contribute to the development and progression of diabetic vascular complications, including atherosclerosis, neuropathy, nephropathy, and retinopathy. In the cardiovascular system, RAGE activation promotes vascular inflammation, endothelial dysfunction, and vascular smooth muscle cell proliferation, all of which are critical in the pathogenesis of atherosclerosis and cardiovascular diseases. Furthermore, RAGE-mediated oxidative stress and inflammation have been implicated in the progression of heart failure and post-ischemic injury. Targeting RAGE signaling thereby emerges as a promising therapeutic approach to mitigate the detrimental effects of chronic hyperglycemia and vascular inflammation in diabetic and cardiovascular diseases. A comprehensive understanding of the multifaceted RAGE functions in cardiovascular complications such as atherosclerosis, peripheral arterial disease, atrial fibrillation, thrombotic disorder, myocardial infarction, vascular calcification, and the role of RAGE in diabetes-associated cardiac fibrosis, is discussed with a focus on therapeutic significance.
The receptor for advanced glycation end products (RAGE) is a multi-ligand receptor molecule expressed in the cells of the nervous system (neurons and glial cells). Compared to embryonic cells, RAGE expression is significantly decreased within the adult tissues, including the nervous system. Various RAGE ligands such as amyloidbeta peptide (Aβ-peptide), high mobility group box protein 1 (HMGB1), S100/calgranulin, and advanced glycation end products (AGEs) are expressed by the cells of the nervous system. Several studies have predicted the role of RAGE in neurogenesis. Interaction of RAGE with its various ligands has been demonstrated as the responsible factor for complicating multiple diseased conditions such as Neuronal Differentiation and Outgrowth, Alzheimer’s Disease (AD), Parkinson’s Disease (PD), Huntington’s Disease (HD), Amyotrophic Lateral Sclerosis (ALS), Creutzfeldt-Jakob’s Disease (CJD), Peripheral Neuropathies, Familial Amyloid Polyneuropathy (FAP), Spinal Cord Injury (SCI), and epilepsy. The interactions of RAGE with its ligands are critically dependent on the relative extents of inflammation and oxidative stress, controlling the various neurological disease manifestations. Redox sensitivity of such interactions is inferred by their treatment using targeted and sustainable antioxidant delivery at the affected regions. Besides targeting RAGE-ligand interactions via blocking RAGE expression may be useful against various neurological diseases.
Nature friendly and sustainable practices have been the prominent aspects reviving the modern agricultural practices. Development of broad spectrum insecticides with the minimal use, maximum efficacy and least environmental deterioration are swiftly emerging as reliable measures. Analogous to drug delivery in animal and human cells, nanocarriers are swiftly emerging as biocompatible and nature friendly aids for pesticide delivery to the agricultural crops. These practices manifest a higher importance for the agriculturally intensive global economies, wherein substantial livelihood means are eventually dependent on agriculture. Amicably transcended from the extraordinary investigational success for drug delivery, trafficking of pesticides through nanoemulsions has emerged as a boost to safeguard the environment and aquatic habitats in particular. The nanoemulsions, with the option of varying surfactant and co-surfactants, engineer the slow release of pesticides which could be targeted for the pest specific elimination. The outcomes have already eased the farmer’s economy besides significantly moderating the toxicity. The threat to soil and surrounding water bodies has been the most significant, wherein almost 90% of the unaided pesticide used to run off as excessive chemical load in the soils or water bodies. The constitutional robustness of emulsions with varied hydrophilic-lipophilic balances and surfactant-co-surfactant stoichiometries have been the distinguishing aspect for the pesticide delivery to the crops. With such insights, this review article focuses on emulsification, the distinguishing working principles, physicochemical characterization driven performance control parameters and finally a discussion of past five year attempts encompassing nanocarrier mediated pesticide delivery for sustainable agriculture and reduced environmental stress.
Conventional drug delivery is swiftly witnessing a shift owing to its saturating deliverance with respect to attaining site-specific delivery of chemotherapeutic drugs. As a consequence, the state of art is being mitigated for minimizing the nonessential interactions with the carriers. Of late, combining drug carriers with stimulus-sensing actuators has been in focus alternative to which is the synergistic ability of carrier–drug combination. In this context, magnetic nanoparticles (MNPs) and polymer nanocomposites (PNCs) are implicit drug carriers, exhibiting significant prospects of a possible synergism. The MNPs-conferred distinction in drug delivery is described by their coupling with external magnetic field, while PNCs exhibit functional robustness via manifold biocompatible polymers as matrix supports. Availability of manifold miniaturizing characterizations with the in silico prediction of binding energies can strengthen the MNPs stoichiometric combinations with PNCs whereby drug–carrier interactions could be moderated. With such insights, the compilation herein advances the possible interfaces of using MNPs and PNCs as synergistic drug carriers.
Ethanol and glycerol being 100 % water soluble hamper free radical scavenging activities (FRSA) of dispersed antioxidants, causing water scarcity as water dipoles balance the zeta-potential and stern layer kinetics. The strong electrolytes reoriented the secondary bonds of ethanol and glycerol to soften a medium resistance for philicphobic continuity attained with Mct.n state function. Herein, NaCl/KCl supplemented, sodium dodecyl sulphate (SDS), tweens (Tw-20 and Tw-40) catalysed cottonseed oil (CSO) nanoformulations in water to monodisperse curcumin (curc), are reported. The Na+, K+, Cl- nanoionic hydration spheres (NHS) have reengaged dipolar water molecules attached with ethanol and glycerol that balance a monodispersity via friccohesity (sigma) enabling (50.61-99.84)% 2,2-diphenyl-1-picrylhydrazyl (DPPH center dot) scavenging. The NHS of Na+, K+, and Cl- have homogenized curc distribution elucidated via surface tension, gamma, viscosity, eta, friccohesity, sigma, isentropic compressibility, kappa s, sound velocity, u and acoustic impedance, Z as binding forces (BF) controls. The (18.08-28.72), (32.82-37.06); (33.80-41.02), (29.36-35.88); (37.80-47.66), (30.13-41.46) gamma with SDS, Tw-20 and Tw-40, have inferred 1.15-3.45 g NaCl and 1.75-5.2 g KCl dispersion activities. Alongside, the (0.020772-0.036525) and (0.022512-0.032197) sigma, as secondary cohesive forces (CF) have revealed NHS shift in SDS-NaCl and Tw-20-KCl formulations. Ninety NaCl/KCl-SDS, Tw-20, Tw-40 permutations enabled (55.84-99.72), (50.60-99.84), (53.81-91.93)% DPPH center dot scavenging at 4.47-7.31 pH. Friccohesity resonance energy transfer (FRET) of optimized nanoformulations depicted H center dot to form H -N bond for DPPH center dot scavenging illustrated with Delta H, Delta S, E-a < 0. The NaCl/KCl could be used with other polyphenols as these have increased surface energy, enabling FRET for intimate proximities.
Of late, promptly responding materials have been the centre-stage of interdisciplinary research. Nanotechnology has emerged as a blessing herein, enabling atomic scale resolution manifested by increasing precision of structural, surface and functionality probing characterizations. Amongst the manifold nanomaterials, nanoparticles (NPs) of transition metals have swiftly emerged as prominent functionality enhancing entities, attributed to quantum confinement (QC) of d sub-shells unpaired electrons encompassed varied oxidation states. Renewable and eco-friendly methods of making NPs have swiftly gathered scientific and academic attention owing to their steadfast workability. In this context, plant extracts (PEs) serve as green reducing agents to obtain zerovalent NMs from complex metal salts. The prepared NPs are recognized initially via QC driven distinct optics and subsequently through explicit structural inspections. The encouraging aspects of plant resources herein include their robust availability and nature-friendly working, ruling out the separate addition of capping agent. Secondary plant metabolites comprise the backbone of PE, making them even more befitting for biological applications. Realizing this, the present article focuses on the structure-function regulated chemistry of CuO NPs with recent advances in their plant resources driven formation. The discussed studies comprise the post 2018 attempts retrieved from the “Pubmed” using the keywords “Bioactivities of Plant Resources Fabricated Copper Oxide Nanoparticles”. The sole objective herein is to understand the diverse applications of CuO NPs vis-à-vis modulated constitutional energy levels and tuneable semi-conducting features. The discussion herein could strengthen the biomedical an environmental utility of integrating renewable plant resources and CuO NPs versatilities for a sustainable future.
Over the past few years, water quality monitoring has swiftly emerged as a thrust area for most of the developing nations. Despite its renewable essence, incessant industrialization and urbanization have depleted the natural water resources, culminating in adverse impact on potable water quality. As a consequence, reliable technologies with utmost sensitivity and accurate predictions vis-à-vis authentic qualitative standards are urgently needed. Herein, interest in using gold nanoparticles (Au NPs) biosensors to gauge the qualitative profile of water resources has been quite significant. Major fascinations for Au NPs biosensing driven water quality monitoring are steadfast preparation methodologies, well-understood mechanisms for size-shape modulation and inert sensitivity manifested remarkable functionalization abilities. The size-shape modulated functionalization advances for Au NPs are the dynamic outcomes of their quantum effects, anchored via single or multidimensional quantum confinements (QCs). Morphologies as vibrant as rod, spherical, cylindrical, shells and combinatorial regime have been the backbone aspects of Au NPs based biosensors. With such insights, the present article focuses on last decade noted advances aimed at Au NPs biosensors assessed water quality. The studies discussed herewith were retrieved from Pubmed using the keywords, “Gold Nanoparticle Biosensors for Water Quality Monitoring”. The knowledge shared herein could consolidate the fabrication of future Au nanomaterials based sensing technologies vis-à-vis functionalization mechanisms, cost considerations, precision aspects, integrated possibilities and long-term cautions.
Despite consistent progress in prompt diagnosis and curative therapies in the last decade, lung cancer (LC) continues to threaten mankind, accounting for nearly twice the casualties compared to prostate, breast, and other cancers. Statistics associate ~25% of 2021 cancer-related deaths with LC, more than 80% of which are explicitly caused by tobacco smoking. Prevailing as small and non-small cell pathologies, with respective occurring frequency of nearly 15% and 80–85%, non-small cell LCs (NSCLCs) are prominently distinguished into lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC), subtypes. Since the first use of epidermal growth factor receptor (EGFR) inhibitor gefitinib for NSCLC treatment in 2002, immense progress has been made for targeted therapies with the next generation of drugs spanning across the chronological generations of small molecule inhibitors. The last two years have overseen the clinical approval of more than 10 therapeutic agents as first-line NSCLC medications. However, uncertain mutational aberrations as well as systemic resistant responses, and abysmal overall survival curtail the combating efficacies. Of late, immune checkpoint inhibitors (ICIs) against various molecules including programmed cell death-1 (PD-1) and its ligand (PD-L1) have been demonstrated as reliable LC treatment targets. Keeping these aspects in mind, this review article discusses the success of NSCLC chemo and immunotherapies with their characteristic effectiveness and future perspectives.
Curcumin, the major polyphenolic ingredient of turmeric (sp. Zingiberaceae), has been well studied for its multifunctional bioactivities, such as antioxidant, anticancer, antidiabetic, anti-inflammatory, etc. Unfortunately, a poor aqueous solubility of this polyphenol mars its adequate physiological absorption despite proven non-toxicity at 12 g per kg dosage, in animal models. Considering this, attempts to deliver this natural bioactive compound through modified carriers have gained swift momentum. Nano or micro emulsions are one of these options which are relatively easy to be prepared, handled, and maneuvered with respect to varying drug dosages. The philicphobic constitutional flexibility of these systems endows them with significant solubility optimization extents, tune able with respect to emulsifier and co-emulsifier selection. The fundamental advantage of these carrier vehicles is the maximization of structural expression from extremely low drug loaded extents. Thereby, these systems not only modulate the drug dosage but also reduce the systemic toxicity. The drug binding capability of these systems is manifested via weaker interactions, such as London Dispersive Forces, van der Waal forces, hydrogen bonding and pi-pi stacking interactions. The fundamental 232essence is to induce sustained vibrations in the native structure without stringent structure making or breaking. Special interest in utilizing these carrier vehicles substantiates from their self-assembly attributes, facilitating dynamic modulation through co-operative chemical activities of constituent fatty acids and their derivatives. Their preparation for drug delivery hardly requires any significant energy from external end, imparting dynamic stability to diverse external stimuli. With such considerations in mind, this compilation discusses the most recent advances towards curcumin nanoemulsification, specifically modulated for antioxidant and anticancer responses.
The earliest documented COVID-19 case caused by the SARS-CoV-2 coronavirus occurred in Wuhan, China, in December 2019. Since then, several SARS-CoV-2 mutants have rapidly disseminated as exemplified by the community spread of the recent omicron variant. The disease already attained a pandemic status with ever-dwindling mortality even after two and half years of identification and considerable vaccination. Aspergillosis, candidiasis, cryptococcosis and mucormycosis are the prominent fungal infections experienced by the majority of SARS-CoV-2 high-risk patients. In its entirety, COVID-19's nexus with these fungal infections may worsen the intricacies in the already beleaguered high-risk patients, making this a topic of substantial clinical concern. Thus, thorough knowledge of the subject is necessary. This article focuses on the concomitant fungal infection(s) in COVID-19 patients, taking into account their underlying causes, the screening methods, manifested drug resistance, and long-term effects. The information and knowledge shared herein could be crucial for the management of critically ill, aged, and immunocompromised SARS-CoV-2 patients who have had secondary fungal infections (SFIs).