The lyotropic liquid crystalline phases of surfactants exhibit a rich polymorphism of structures that have long-range periodicities and whose characteristic repeat distances range from 2 to 15 ...nanometers. The electrochemical reduction of platinum salts confined to the aqueous environments of these phases leads to the deposition of platinum films that have a well-defined long-ranged porous nanostructure and high specific surface areas. These results suggest that the use of liquid crystalline plating solutions could be a versatile way to create mesoporous electrodes for batteries, fuel cells, electrochemical capacitors, and sensors.
Cancer is characterized by uncontrolled cell growth, disrupted regulatory pathways, and the accumulation of genetic mutations. These mutations across different types of cancer lead to disruptions in ...signaling pathways and alterations in protein expression related to cellular growth and proliferation. This review highlights the AKT signaling cascade and the retinoblastoma protein (pRb) regulating cascade as promising for novel nanotheranostic interventions. Through synergizing state-of-the-art gene editing tools like the Clustered Regularly Interspaced Short Palindromic Repeats (CRISPR)-Cas system with nanomaterials and targeting AKT, there is potential to enhance cancer diagnostics significantly. Furthermore, the integration of modified CAR-T cells into multifunctional nanodelivery systems offers a promising approach for targeted cancer inhibition, including the eradication of cancer stem cells (CSCs). Within the context of highly aggressive and metastatic Triple-negative Breast Cancer (TNBC), this review specifically focuses on devising innovative nanotheranostics. For both pre-clinical and post-clinical TNBC detection, the utilization of the CRISPR-Cas system, guided by RNA (gRNA) and coupled with a fluorescent reporter specifically designed to detect TNBC's mutated sequence, could be promising. Additionally, a cutting-edge approach involving the engineering of TNBC-specific iCAR and syn-Notch CAR T-cells, combined with the co-delivery of a hybrid polymeric nano-liposome encapsulating a conditionally replicative adenoviral vector (CRAdV) against CSCs, could present an intriguing intervention strategy. This review thus paves the way for exciting advancements in the field of nanotheranostics for the treatment of TNBC and beyond.
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Toward the end of the nineteenth century a complex of problems related to ticks and tick-borne diseases of cattle created a demand for methods to control ticks and reduce losses of cattle. The ...discovery and use of arsenical solutions in dipping vats for treating cattle to protect them against ticks revolutionized tick and tick-borne disease control programmes. Arsenic dips for cattle were used for about 40 years before the evolution of resistance of ticks to the chemical, and the development and marketing of synthetic organic acaricides after World War II provided superior alternative products. Most of the major groups of organic pesticides are represented on the list of chemicals used to control ticks on cattle. Unfortunately, the successive evolution of resistance of ticks to acaricides in each chemical group with the concomitant reduction in the usefulness of a group of acaricides is a major reason for the diversity of acaricides. Whether a producer chooses a traditional method for treating cattle with an acaricide or uses a new method, he must recognize the benefits, limitations and potential problems with each application method and product. Simulation models and research were the basis of recommendations for tick control strategies advocating approaches that reduced reliance on acaricides. These recommendations for controlling ticks on cattle are in harmony with recommendations for reducing the rate of selection for acaricide resistance. There is a need to transfer knowledge about tick control and resistance mitigation strategies to cattle producers.
The extremely widespread and ubiquitous nature of plastics, estimated to boost its global production by 26 billion tons till 2050. The large chunks of plastic waste that decomposed down to micro- or ...nano plastics (MNPs) leads to various ill effects on biological entities. The conventional PET detection methods lack rapid detection of microplastics due to variances in microplastic features, long-drawn-out sample pre-processing procedures and complex instrumentation. Therefore, an instantaneous colorimetric evaluation of microplastic will ensures the simplicity of conducting assays on field. Several nanoparticle-based biosensors that detects proteins, nucleic acids, metabolites operate on either cluster or disperse state of nanoparticle. However, gold nanoparticle (AuNPs) emerges an ideal scaffold for sensory element in lateral flow biosensors due to their simple surface functionalization, unique optoelectronic properties and varied colour spectrum depending on morphologies and aggregation state. In this paper an effort has been made in the form of a hypothesis using in silico tools as a basis to detect polyethylene terephthalate (PET) – most abundant type of microplastic using gold nanoparticle based lateral flow biosensor. We retrieved sequences of PET-binding synthetic peptides and modelled their 3-D structure using I-Tasser server. The best protein model for each peptide sequences are docked with PET monomers – BHET, MHET and other PET polymeric ligands, to evaluate their binding affinities. The synthetic peptide SP 1 (WPAWKTHPILRM) docked with BHET and (MHET)4 exhibits 1.5-fold increases in binding affinity as compared to reference PET anchor peptide Dermaseptin SI (DSI). The GROMACS molecular dynamics simulation studies of synthetic peptide SP 1 - BHET & - (MHET)4 complexes for 50 ns further confirmed the stable binding. RMSF, RMSD, hydrogen bonds, Rg and SASA analysis provides useful structural insights of the SP 1 complexes as compared to reference DSI. Furthermore, SP 1 functionalized AuNP-based colorimetric device was described in detail for detection of PET.
•AutoDock Vina for screening out novel PET binding anchor peptides.•Molecular Dynamics simulation illustrates PET - SP 1 structural stability.•Synthetic peptide functionalized AuNPs based colorimetric PET biosensor.
Abstract Objective Plasma adiponectin is strongly associated with various components of metabolic syndrome, type 2 diabetes and cardiovascular outcomes. Concentrations are highly heritable and differ ...between men and women. We therefore aimed to investigate the genetics of plasma adiponectin in men and women. Methods We combined genome-wide association scans of three population-based studies including 4659 persons. For the replication stage in 13795 subjects, we selected the 20 top signals of the combined analysis, as well as the 10 top signals with p -values less than 1.0 × 10−4 for each the men- and the women-specific analyses. We further selected 73 SNPs that were consistently associated with metabolic syndrome parameters in previous genome-wide association studies to check for their association with plasma adiponectin. Results The ADIPOQ locus showed genome-wide significant p -values in the combined ( p = 4.3 × 10−24 ) as well as in both women- and men-specific analyses ( p = 8.7 × 10−17 and p = 2.5 × 10−11 , respectively). None of the other 39 top signal SNPs showed evidence for association in the replication analysis. None of 73 SNPs from metabolic syndrome loci exhibited association with plasma adiponectin ( p > 0.01). Conclusions We demonstrated the ADIPOQ gene as the only major gene for plasma adiponectin, which explains 6.7% of the phenotypic variance. We further found that neither this gene nor any of the metabolic syndrome loci explained the sex differences observed for plasma adiponectin. Larger studies are needed to identify more moderate genetic determinants of plasma adiponectin.
Summary
We conducted a Cochrane systematic review on the effectiveness of supplemental intravenous crystalloid administration in preventing postoperative nausea and vomiting. We included randomised ...controlled trials of patients undergoing surgery under general anaesthesia and given supplemental peri‐operative intravenous crystalloid. Our primary outcomes were the risk of postoperative nausea and the risk of postoperative vomiting. We assessed the risk of bias for each included study and applied the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) framework for the certainty of evidence. We included 41 studies. We found that the intervention probably reduces the overall risk of postoperative nausea, the risk ratio (95%CI) being 0.62 (0.51–0.75) (I2 = 57%, p < 0.00001, 18 studies; 1766 participants; moderate‐certainty evidence). It also probably reduces the risk of postoperative nausea within 6 h of surgery, with a risk ratio (95%CI) of 0.67 (0.58 to 0.78) (I2 = 9%, p < 0.00001, 20 studies; 2310 participants; moderate‐certainty evidence) and by around 24 h, the risk ratio (95%CI) being 0.47 (0.32–0.69) (I2 = 38%, p = 0.0001, 17 studies; 1682 participants; moderate‐certainty evidence). Supplemental intravenous crystalloid probably also reduces the overall risk of postoperative vomiting, with a risk ratio (95%CI) of 0.50 (0.40–0.63) (I2 = 31%, p < 0.00001, 20 studies; 1970 participants; moderate‐certainty evidence). The beneficial effect on vomiting was seen both within 6 h and by around 24 h postoperatively.
We describe a novel sequencing approach that combines non-gel-based signature sequencing with in vitro cloning of millions of templates on separate 5 microm diameter microbeads. After constructing a ...microbead library of DNA templates by in vitro cloning, we assembled a planar array of a million template-containing microbeads in a flow cell at a density greater than 3x10(6) microbeads/cm2. Sequences of the free ends of the cloned templates on each microbead were then simultaneously analyzed using a fluorescence-based signature sequencing method that does not require DNA fragment separation. Signature sequences of 16-20 bases were obtained by repeated cycles of enzymatic cleavage with a type IIs restriction endonuclease, adaptor ligation, and sequence interrogation by encoded hybridization probes. The approach was validated by sequencing over 269,000 signatures from two cDNA libraries constructed from a fully sequenced strain of Saccharomyces cerevisiae, and by measuring gene expression levels in the human cell line THP-1. The approach provides an unprecedented depth of analysis permitting application of powerful statistical techniques for discovery of functional relationships among genes, whether known or unknown beforehand, or whether expressed at high or very low levels.
Patients with generalized social phobia fear embarrassment in most social situations. Little is known about its functional neuroanatomy. We studied BOLD-fMRI brain activity while generalized social ...phobics and healthy controls anticipated making public speeches. With anticipation minus rest, 8 phobics compared to 6 controls showed greater subcortical, limbic, and lateral paralimbic activity (pons, striatum, amygdala/uncus/anterior parahippocampus, insula, temporal pole)--regions important in automatic emotional processing--and less cortical activity (dorsal anterior cingulate/prefrontal cortex)--regions important in cognitive processing. Phobics may become so anxious, they cannot think clearly or vice versa.
Drug delivery to tumors suffers from poor solubility, specificity, diffusion through the tumor micro‐environment and nonoptimal interactions with components of the extracellular matrix and cell ...surface receptors. Nanoparticles and drug–polymer complexes address many of these problems. However, large size exasperates the problem of slow diffusion through the tumor. Three‐dimensional tumor spheroids are good models to evaluate approaches to mitigate these difficulties and aid in design strategies to improve the delivery of drugs to treat cancer effectively. Diffusion of drug carriers is highly dependent on cell uptake rate parameters (association/dissociation) and temperature. Hyperthermia increases molecular transport and is known to act synergistically with chemotherapy to improve treatment. This study presents a new inverse estimation approach based on Bayesian probability for estimating nanoparticle cell uptake rates from experiments. The parameters were combined with a finite element computational model of nanoparticle transport under hyperthermia conditions to explore its effect on tumor porosity, diffusion and particle binding (association and dissociation) at cell surfaces. Carboxy‐PEG‐silane (cPEGSi) nanoparticles showed higher cell uptake compared to methoxy‐PEG‐silane (mPEGSi) nanoparticles. Simulations were consistent with experimental results from Skov‐3 ovarian cancer spheroids. Amorphous silica (cPEGSi) nanoparticles (58 nm) concentrated at the periphery of the tumor spheroids at 37°C but mild hyperthermia (43°C) increased nanoparticle penetration. Thus, hyperthermia may enhance cancer treatment by improving blood delivery to tumors, enhancing extravasation and penetration into tumors, trigger release of drug from the carrier at the tumor site and possibly lead to synergistic anti‐cancer activity with the drug.
Carboxy‐PEG‐silane functionalized silica nanoparticle transport through Skov‐3 ovarian tumor spheroids under normal temperature and hyperthermia conditions was modeled by (i) solving Fick's equation with reaction terms, (ii) modeling heat generation and thermal damage to cells, (iii) calculating changes in porosity of the spheroid and membrane rate constants, and (iv) iterating until the stopping criteria is reached. The model accurately predicted the experimentally observed increase in nanoparticle tumor penetration at 43°C compared to 37°C.
BACKGROUNDAlzheimer's disease (AD) is characterized by neuroinflammation linked to amyloid β (Aβ) aggregation and phosphorylated tau (τ) protein in neurofibrillary tangles (NFTs). Key elements in Aβ ...production and NFT assembly, like γ-secretase and p38 mitogen-activated protein kinase (p38MAPK), contribute to neuroinflammation. In addition, impaired proteosomal and autophagic pathways increase Aβ and τ aggregation, leading to neuronal damage. Conventional neuroinflammation drugs have limitations due to unidirectional therapeutic approaches and challenges in crossing the Blood-Brain Barrier (BBB). Clinical trials for non-steroidal anti-inflammatory drugs (NSAIDs) and other therapeutics remain uncertain. Novel strategies addressing the complex pathogenesis and BBB translocation are needed to effectively tackle AD-related neuroinflammation.PURPOSEThe current scenario demands for a much-sophisticated theranostic measures which could be achieved via customized engineering and designing of novel nanotherapeutics. As, these therapeutics functions as a double edge sword, having the efficiency of unambiguous targeting, multiple drug delivery and ability to cross BBB proficiently.METHODSInclusion criteria involve selecting recent, English-language studies from the past decade (2013-2023) that explore the regulation of neuroinflammation in neuroinflammation, Alzheimer's disease, amyloid β, tau protein, nanoparticles, autophagy, and phytocompounds. Various study types, including clinical trials, experiments, and reviews, were considered. Exclusion criteria comprised non-relevant publication types, studies unrelated to Alzheimer's disease or phytocompounds, those with methodological flaws, duplicates, and studies with inaccessible data.RESULTSIn this study, polymeric nanoparticles loaded with specific phytocompounds and coated with an antibody targeting the transferrin receptor (anti-TfR) present on BBB. Thereafter, the engineered nanoparticles with the ability to efficiently traverse the BBB and interact with target molecules within the brain, could induce autophagy, a cellular process crucial for neuronal health, and exhibit potent anti-inflammatory effects. Henceforth, the proposed combination of desired phytocompounds, polymeric nanoparticles, and anti-TfR coating presents a promising approach for targeted drug delivery to the brain, with potential implications in neuroinflammatory conditions such as Alzheimer's disease.
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