Unhealthy Cells Research Articles

Optical property discrepancies found between healthy and unhealthy skin cells using digital holographic microscopy with three wavelengths

Cancer and other health disorders can be differentiated by changes in cell optical properties such as their refractive index, thickness, and topology (height and width). Here, we employ three wavelengths simultaneously in digital holographic microscopy (3λ-DHM) to visualize the whole cell topology as 3D images through a numerical reconstruction algorithm applied to a hologram. By identifying the cell state and the changes in its optical properties, it is possible to discern between healthy and unhealthy cells. The simultaneous use of three wavelengths provides a rapid and straightforward quantitative reconstruction of the whole cell without the need for an unwrapping algorithm. This is a benefit over traditional methods, which often require complicated procedures. The performance of the approach was first validated in a known sample, a silicon dioxide thin film, where we were able to corroborate its refractive index with the values reported in the literature. Then the method was applied to fixed skin cells finding a refractive index of 1.3443 for healthy cells and 1.3246 for cells found in tumor tissue. We discuss and highlight differences based on the refractive index to demonstrate that the employed process can provide reliable information to distinguish characteristics between healthy and unhealthy cells.

An Investigation into the Viability of Cell-Level Temperature Control in Lithium-Ion Battery Packs

Abstract This article focuses on the thermal management and temperature balancing of lithium-ion battery packs. As society transitions to relying more heavily on renewable energy, the need for energy storage rises considerably, as storage facilitates power regulation between these sources and the grid. Lithium-ion batteries are leading the market for energy storage options, but their properties are temperature sensitive, with thermal abuse resulting in shortened pack lifetime and possible safety issues. Current battery thermal management systems (BTMS) are implemented in a number of ways to ensure consistent and reliable operation. However, they are typically limited in architecture and restricted in ability to attend to temperature gradients. This work proposes a BTMS topology that permits control of the individual cooling received by a cell in a pack. First, an analysis is done using timescale separation to confirm that cell-level temperature control is capable of extending the lifetime of a pack as compared to pack-level control. The analysis is used to guide the gain tuning of a state feedback controller, which directs more cooling effort to cells of higher temperatures. Validation of the BTMS topology and control is performed through the simulation of a battery pack, with variations in total cooling power and resistance heterogeneity. The outcome of the validation studies indicates that the proposed BTMS configuration is better equipped to reduce temperature differences and extend pack life. This benefit increases as total input power increases, giving the controller more freedom to cool unhealthy cells while remaining within power constraints.

Enhanced breast tumor localization with DRA antenna backscattering and GPR algorithm in microwave imaging

With the rapid rate of increasing breast cancer cases across the globe and restrictions of existing early stage detection techniques, microwave imaging based cancer and malignant cell diagnosing methodology is finding its way. Microwave imaging technology has higher accuracy of detection in the variation of tissue properties. In this article, a dielectric resonator based wide band antenna is designed and investigated for microwave imaging (MWI) of early breast cancer detection due to its improved accuracy. The designed antenna has compact size, broad frequency spectrum, high gain and broadside radiation characteristics. To attain the wider bandwidth from (6.5 GHz–12.5 GHz), two rectangular shaped dielectric slabs are used. Wide band microwave frequency band supports the high resolution images. A C-shaped defected ground structure is used to tune the impedance matching. Dielectric resonator based antenna has higher gain and reduces the squints in antenna impedance. Two-asymmetrical dielectric slabs contribute in the excitation of different resonating modes which in turn enhance the bandwidth. It also contributes to excite multiple resonance mode that in turn enhance the bandwidth. Antenna performance is first numerically and experimentally verified in free space. Then, simulation based performance is examined for the microwave imaging. Numerical phantom with equivalent tissue properties is designed with and without the tumor. Unhealthy cells have higher water percentage and larger dielectric constant as compared to healthy cells. It causes the different in the back scattered signal of antenna, which is analyzed to diagnose the tumor or cancer. Here, a maximum deviation of 16 dB is observed in the backscattered signal. Furthermore, surface of the breast tissue is scanned along the x-axis and y-axis at different angels. The collected signals are used to reconstruct the microwave image of the interior. Mean value data of backscattered signals is used to locate the existence of unhealthy cells and GPR algorithm is used to calculate the depth of a 4 mm tumor in breast tissue. Proposed structure has shown efficient performance for microwave imaging.

Comparison of Regression Methods to Predict the First Spike Latency in Response to an External Stimulus in Intracellular Recordings for Cerebellar Cells.

The significance of intracellular recording in neurophysiology is emphasized in this article, with considering the functions of neurons, particularly the role of first spike latency in response to external stimuli. The study employs advanced machine learning techniques to predict first spike latency from whole cell patch recording data. Experiments were conducted on Control (Salin) and Experiment (Harmaline) groups, generating a dataset for developing predictive models. Because the dataset has a limited number of samples, we utilized models that are effective with small datasets. Among different groups of regression models (linear, ensemble, and tree models), the ensemble models, specifically the LGB method, can achieve better performance. The results demonstrate accurate prediction of first spike latency, with an average mean squared error of 0.0002 and mean absolute error of 0.01 in 10-fold cross-validation. The research suggests the potential of machine learning in forecasting the first spike latency, allowing reliable estimation without the need for extensive animal testing. This intelligent predictive system facilitates efficient analysis of first spike latency changes in both healthy and unhealthy brain cells, streamlining experimentation and providing more detailed insights into the captured signals.

Parsing digital or analog TCR performance through piconewton forces.

αβ T cell receptors (TCRs) principally recognize aberrant peptides bound to major histocompatibility complex molecules (pMHCs) on unhealthy cells, amplifying specificity and sensitivity through physical load placed on the TCR-pMHC bond during immunosurveillance. To understand this mechanobiology, TCRs stimulated by abundantly and sparsely arrayed epitopes (NP366-374/Db and PA224-233/Db, respectively) following in vivo influenza A virus infection were studied with optical tweezers. While certain NP repertoire CD8 T lymphocytes require many ligands for activation, others are digital, needing just few. Conversely, all PA TCRs perform digitally, exhibiting pronounced bond lifetime increases through sustained, energizing volleys of structural transitioning. Optimal digital performance is superior in vivo, correlating with ERK phosphorylation, CD3 loss, and activation marker up-regulation in vitro. Given neoantigen array paucity, digital TCRs are likely critical for immunotherapies.

Adding metabolic tasks to human GEM models to improve the study of gene targets and their associated toxicities

Genetic minimal cut sets (gMCS) are genes that must be deactivated simultaneously to avoid unwanted states in a metabolic model. The concept of gMCS can be applied to two different scenarios. First, it can be used to identify potential gene toxicities in generic or healthy cell models. Second, it can be used to develop genetic strategies to target cancer cells and prevent their proliferation. Up to now, gMCS have been evaluated using the traditional procedure of preventing biomass production. This paper proposes an additional way: using essential metabolic tasks, which any human cell should perform, to enlarge the set of unwanted states. Including this addition can significantly improve the study of toxicities and reveal targets that can be used to treat unhealthy cells. Excluding metabolic tasks can cause important information to be overlooked, which could impact the study’s success. Regarding toxicities, using the generic Human model, the number of detected generic toxicities with metabolic tasks increases from 106 to 281 (136 gMCSs of length 1 and 49 of length 2). We have used the following context-specific models to evaluate specific toxicities in different healthy tissues: blood, pancreas, liver, heart, and kidney. Again, considering metabolic tasks, we have found new toxicities (lengths 1 and 2) whose inactivation could damage these healthy tissues.Our research strategy has been applied to identify new cancer drug targets in two myeloma cell lines. We obtained new therapeutic targets of lengths 1 and 2 for each cell line. After analyzing the data, we conclude that incorporating metabolic tasks into cancer models can reveal important therapeutic targets previously disregarded by the conventional method of inhibiting biomass production. This approach also improves the evaluation of potential drug toxicities.

Crossover smell agent optimized multilayer perceptron for precise brain tumor classification on MRI images

The Brain tumor is considered an unusual growth of cells in the nervous system that restricts the normal functionality of the brain. However, is generated in the skull and pressures the brain which affects the health of a person. So it is essential to detect and classify the brain tumor at an early stage before reaching the severity level. Meanwhile, brain tumor detection is performed based on MRI images which are considered an effective diagnosis system. But the detection and classification using MRI images is obtained as a complex task and cannot show the difference between normal and abnormal cells. So to overcome this issue the Crossover Smell Agent Optimized Multilayer Perception (CSA-MLP) is proposed to perform the exact detection and classification of tumor cells from MRI images. The images are collected from three datasets namely MR, Brain MRI, and Brain tumor datasets and they are preprocessed to remove the unwanted noise. After preprocessing the features of the images are extracted to perform the classification process. Moreover, the Convolutional Neural Network (CNN) classifier is used to classify healthy and unhealthy brain cells. The Multi-Layer Perceptron (MLP) is employed for the classification category that minimized the errors and enhanced the performance of the proposed method. The MLP is integrated with the CSA optimization algorithm to improve classification accuracy. The experimentation results revealed that the proposed method achieved a better accuracy of about 98.56% which enhanced the effectiveness compared to existing methods.

An inference model gives insights into innate immune adaptation and repertoire diversity

The innate immune system is the body's first line of defense against infection. Natural killer (NK) cells, a vital part of the innate immune system, help to control infection and eliminate cancer. Studies have identified a vast array of receptors that NK cells use to discriminate between healthy and unhealthy cells. However, at present, it is difficult to explain how NK cells will respond to novel stimuli in different environments. In addition, the expression of different receptors on individual NK cells is highly stochastic, but the reason for these variegated expression patterns is unclear. Here, we studied the recognition of unhealthy target cells as an inference problem, where NK cells must distinguish between healthy targets with normal variability in ligand expression and ones that are clear "outliers." Our mathematical model fits well with experimental data, including NK cells' adaptation to changing environments and responses to different target cells. Furthermore, we find that stochastic, "sparse" receptor expression profiles are best able to detect a variety of possible threats, in agreement with experimental studies of the NK cell repertoire. While our study was specifically motivated by NK cells, our model is general and could also apply more broadly to explain principles of target recognition for other immune cell types.

Correlation of PDL-1 Expression with Tumour Budding and Tumour Infiltrating Lymphocytes in Colorectal Cancers

Objective: To study and correlate PDL-1 expression with Tumour budding and Tumour Infiltrating Lymphocytes in Colorectal Carcinoma. Background: Colorectal cancer (CRC) is third most common cancer with a high mortality. Many attempts have been made to raise overall survival of CRC patients. The immune system plays an important role in clearing the unhealthy cancer cells. Programmed death 1 (PD1) is a regulatory molecule which dampens the immune response when bound to one of its complementary ligands (PDL1). Its expression is related to the response of immunotherapy in CRC treatment which has been exploited in recent times. However, its prognostic value is still controversial, and the distribution of PD-L1 on tumour Cells or Immune Cells has not been comprehensively analysed. Method: A total of 30 patients diagnosed with CRCs were included who underwent surgical intervention. Cases who took preoperative neoadjuvant chemotherapy or radiotherapy were excluded. IHC analyses of PDL1 was done and was correlated with tumour budding and Tumour Infiltrating Lymphocytes (TILs) and statistical significance was assessed. Results: 11 cases showed low bud count at the invasive front out of which only 3 cases showed PDL1 positivity. The rest 19 cases had high bud count out of which 18 were PDL 1 positive. This difference was highly significant (p = 0.002). In Low Bud / High TILs, 75% cases showed no PDL1 expression in tumour cells, whereas 62.5% cases showed PDL1 positivity in TILs whereas in High Bud / Low TILs group, all the cases (100%) showed PDL1 expression in tumour cells whereas only 75% cases showed PDL1 positivity in TILs, again being statistically significant (p <0.001). Conclusion: This study showed an inverse correlation between PDL1 in tumour buds and immune cells, thus emphasising the role of tumour microenvironment. Our study reiterates the fact that high expression of PDL1 in tumour cells suppresses antitumor response whereas its high expression in TILS correlates with a better prognosis.

Boosting the photodynamic activity of erythrosine B by using thermoresponsive and adhesive systems containing cellulose derivatives for topical delivery

Erythrosine displays potential photodynamic activity against microorganisms and unhealthy cells. However, erythrosine has high hydrophilicity, negatively impacting on permeation through biological membranes. Combining biological macromolecules and thermoresponsive polymers may overcome these erythrosine-related issues, enhancing retention of topically applied drugs. The aim of this work was to investigate the performance of adhesive and thermoresponsive micellar polymeric systems, containing erythrosine in neutral (ERI) or disodium salt (ERIs) states. Optimized combinations of poloxamer 407 (polox407) and sodium carboxymethylcellulose (NaCMC) or hydroxypropyl methylcellulose (HPMC) were used as platforms for ERI/ERIs delivery. The rheological and mechanical properties of the systems was explored. Most of the formulations were plastic, thixotropic and viscoelastic at 37 °C, with suitable gelation temperature for in situ gelation. Mechanical parameters were reduced in the presence of the photosensitizer, improving the softness index. Bioadhesion was efficient for all hydrogels, with improved parameters for mucosa in contrast to skin. Formulations composed of 17.5 % polox407 and 3 % HPMC or 1 % NaCMC with 1 % (w/w) ERI/ERIs could release the photosensitizer, reaching different layers of the skin/mucosa, ensuring enough production of cytotoxic species for photodynamic therapy. Functional micelles could boost the photodynamic activity of ERI and ERIs, improving their delivery and contact time with the cells.

Cycas pectinata stimulates germ cell proliferation in mouse testes

Cycas pectinata has been used traditionally by indigenous tribes in the North Eastern region of India. The seed of Cycas pectinata are eaten by local communities as a source of starch and microsporophylls to improve male sexual potency. However, there is no scientific evidence on its testicular physiology. Thus, present study examined the effect of Cycas pectinata seed extract (CPE) on testicular activity in the testis of adult mice. The methanolic extract of Cycas pectinata seed (CPE) was prepared and its composition has already been reported earlier. CPE was orally given in two doses 100 and 400 mg/kg for 35 days and male reproductive endpoints were monitored. CPE significantly increased sperm parameters, antioxidant status and germ cell proliferation compared to the control. CPE decreased the expression of NF-κB and BCl2 and increased the abundance of active caspase-3. Expression of ERα and β were down-regulated and expression of AR was elevated in the CPE-treated mice testis. Therefore, CPE improves sperm concentration and germ cell proliferation by enhancing the antioxidant status of the testis. CPE might also be involved in the removal of damaged or unhealthy germ cells and the overall effect of CPE could be mediated via AR signalling.

Insights on plasma membrane asymmetry from studies of asymmetric model membranes.

Cells spend a lot of energy to maintain the plasma membrane as asymmetric, with distinct leaflet compositions. In contrast, unhealthy cells, or cells with a signal to die, typically lose this asymmetry. Certainly, cells would evolve to such high complexity for a purpose. Studies in model membranes with rationally simplified lipid composition point to an exoplasmic model leaflet with coexistence of liquid disordered (Ld) and liquid ordered (Lo) phases. The apposed cytoplasmic leaflet lacks the large fraction of high melting lipids needed to sustain phase separation. To investigate properties of the plasma membrane asymmetry, we use a new method to engineer asymmetric bilayers by hemifusion between giant unilamellar vesicles (GUVs) and a supported lipid bilayer (SLB). The newly exchanged lipids from the SLB replace the lipids on the GUV outer leaflet, forming asymmetric vesicles (aGUVs). Little perturbation was observed in the vesicle content of these aGUVs. We assemble a phase-separated Ld+Lo leaflet apposed to a leaflet with a uniform Ld composition. For several different lipid mixtures, we observe an ordered phase inducing exactly apposed order on the fluid leaflet. Even with the challenge to track cholesterol movements, our results suggest a composition change, in which induced order domains become enriched with cholesterol. This result brings a new picture and a significant implication for the plasma membrane: The cytoplasmic leaflet has “raft-like” domains induced by the exoplasmic leaflet. Membrane-bound molecules in the cytoplasmic leaflet that can move laterally must partition between disordered regions and induced order regions, as we observe with lipid dyes. Based on line tension estimates, we explain why the induced order domains would be macroscopic domains, or modulated phases, or else nanodomains.

Quantum Dots: Targeted and Traceable Drug Delivery System

“Quantum dots (QD’s) are semiconductor crystals of nanometre dimensions with distinctive conductive properties determined by its size”. If the semiconductor particle area unit is created sufficiently small, quantum effects get to play. When UV light hits these conductive nanoparticles, they will emit light of varied colors and these colors will be varied by dominant the dimensions of nanoparticles. Traditional imaging models like MRI andPET are less sensitive compared to optical imaging done using QD’s which is significantly cheaper, cost-effective and shortens the time required for drug development. Earlier QD’s were cadmium based which provides it with unique photonic properties and photonic stability but because of its toxicity, it is replaced with alternative materials like germanium, silicon and carbon. The structure of QD’s contains a core that is a structural scaffold and imaging distinction agent. Small hydrophobic molecules can be embedded in between the inorganic core and amphiphilic polymer coating layer, hydrophilic agents can be immobilized in the hydrophilic end of the amphiphilic polymer through covalent and non-covalent bonds. This kind of nanostructures acts as a magic bullet that not solely identifies, binds to the targeted unhealthy cells however additionally emits detectable signals that help in the real-time tracking.

Regenerative medicine improve neurodegenerative diseases.

Regenerative medicine is a subdivision of medicine that improves methods to regrow, repair or replace unhealthy cells and tissues to return to normal function. Cell therapy, gene therapy, nanomedicine as choices used to cure neurodegenerative disease. Recently, studies related to the treatment of neurodegenerative disorders have been focused on stem cell therapy and Nano-drugs beyond other than regenerative medicine. Hence, by data from experimental models and clinical trials, we review the impact of stem cell therapy, gene therapy, and nanomedicine on the treatment of Alzheimer's disease (AD), Parkinson's disease (PD), and Amyotrophic lateral sclerosis (ALS). Indeed, improved knowledge and continued research on gene therapy and nanomedicine in treating Alzheimer's disease, Parkinson's disease, and Amyotrophic lateral sclerosis lead to advancements in effective and practical treatments for neurodegenerative diseases.

Anti-SOD1 Nanobodies That Stabilize Misfolded SOD1 Proteins Also Promote Neurite Outgrowth in Mutant SOD1 Human Neurons.

ALS-linked mutations induce aberrant conformations within the SOD1 protein that are thought to underlie the pathogenic mechanism of SOD1-mediated ALS. Although clinical trials are underway for gene silencing of SOD1, these approaches reduce both wild-type and mutated forms of SOD1. Here, we sought to develop anti-SOD1 nanobodies with selectivity for mutant and misfolded forms of human SOD1 over wild-type SOD1. Characterization of two anti-SOD1 nanobodies revealed that these biologics stabilize mutant SOD1 in vitro. Further, SOD1 expression levels were enhanced and the physiological subcellular localization of mutant SOD1 was restored upon co-expression of anti-SOD1 nanobodies in immortalized cells. In human motor neurons harboring the SOD1 A4V mutation, anti-SOD1 nanobody expression promoted neurite outgrowth, demonstrating a protective effect of anti-SOD1 nanobodies in otherwise unhealthy cells. In vitro assays revealed that an anti-SOD1 nanobody exhibited selectivity for human mutant SOD1 over endogenous murine SOD1, thus supporting the preclinical utility of anti-SOD1 nanobodies for testing in animal models of ALS. In sum, the anti-SOD1 nanobodies developed and presented herein represent viable biologics for further preclinical testing in human and mouse models of ALS.

Discrimination of normal and cancerous human skin tissues based on laser-induced spectral shift fluorescence microscopy

A homemade spectral shift fluorescence microscope (SSFM) is coupled with a spectrometer to record the spectral images of specimens based on the emission wavelength. Here a reliable diagnosis of neoplasia is achieved according to the spectral fluorescence properties of ex-vivo skin tissues after rhodamine6G (Rd6G) staining. It is shown that certain spectral shifts occur for nonmelanoma/melanoma lesions against normal/benign nevus, leading to spectral micrographs. In fact, there is a strong correlation between the emission wavelength and the sort of skin lesions, mainly due to the Rd6G interaction with the mitochondria of cancerous cells. The normal tissues generally enjoy a significant red shift regarding the laser line (37 nm). Conversely, plenty of fluorophores are conjugated to unhealthy cells giving rise to a relative blue shift i.e., typically SCC (6 nm), BCC (14 nm), and melanoma (19 nm) against healthy tissues. In other words, the redshift takes place with respect to the excitation wavelength i.e., melanoma (18 nm), BCC (23 nm), and SCC (31 nm) with respect to the laser line. Consequently, three data sets are available in the form of micrographs, addressing pixel-by-pixel signal intensity, emission wavelength, and fluorophore concentration of specimens for prompt diagnosis.

Photoinduced Carbene for Effective Photodynamic Therapy Against Hypoxic Cancer Cells

Photoinduced Carbene for Effective Photodynamic Therapy Against Hypoxic Cancer Cells

The people behind the papers - Adélaïde Allais and Greg FitzHarris.

Aneuploidy is relatively common in mammalian preimplantation embryos, due to chromosome segregation errors in mitosis. A new paper in Development investigates whether the mitotic timer mechanism, a checkpoint that detects prolonged M phase, which may indicate an unhealthy cell division, is active in preimplantation mouse embryos. We caught up with first author Adélaïde Allais and corresponding author Greg FitzHarris (Professor at the Université de Montréal) to find out more about their research.

CXCR4/CXCL12 Activities in the Tumor Microenvironment and Implications for Tumor Immunotherapy.

Simple SummaryChemokines are small soluble proteins that control and regulate cell trafficking within and between tissues by binding to their receptors. Among them, CXCL12 and its receptor CXCR4 appeared with ancestral vertebrates, are expressed almost ubiquitously, and play essential roles in embryogenesis and organogenesis. In addition, CXCL12 and CXCR4 are involved in antigen recognition by T and B cells and in shaping the tumor microenvironment (TME), mainly towards dampening immune responses. New data indicate that CXCR4 interacts with the surface protein CD47 in a novel form of immunosurveillance, called ImmunoGenic Surrender (IGS). Following the co-internalization of CXCR4 and CD47 in tumor cells, macrophages phagocytose them and cross-present their antigens to the adaptive immune system, leading to tumor rejection in a fraction of mice. All of these specific activities of CXCL12 and CXCR4 in antigen presentation might be complementary to current immunotherapies.CXCR4 is a G-Protein coupled receptor that is expressed nearly ubiquitously and is known to control cell migration via its interaction with CXCL12, the most ancient chemokine. The functions of CXCR4/CXCL12 extend beyond cell migration and involve the recognition and disposal of unhealthy or tumor cells. The CXCR4/CXCL12 axis plays a relevant role in shaping the tumor microenvironment (TME), mainly towards dampening immune responses. Notably, CXCR4/CXCL12 cross-signal via the T and B cell receptors (TCR and BCR) and co-internalize with CD47, promoting tumor cell phagocytosis by macrophages in an anti-tumor immune process called ImmunoGenic Surrender (IGS). These specific activities in shaping the immune response might be exploited to improve current immunotherapies.

Glyco-nanotechnology: A biomedical perspective

Glycans govern cellular signaling through glycan–protein and glycan–glycan crosstalk. Disruption in the crosstalk initiates ‘rogue’ signaling and pathology. Nanomaterials supply platforms for multivalent displays of glycans, mediate ‘rogue’ signal correction, and provide disease treatment modalities (therapeutics). The decorated glycans also target overexpressed lectins on unhealthy cells and direct metal nanoparticles such as gold, iron oxide, and quantum dots to the site of infection. The nanoparticles inform us about the state of the disease (diagnosis) through their distinct optical, magnetic, and electronic properties. Glyco-nanoparticles can sense disease biomarkers, report changes in protein–glycan interactions, and safeguard quality control (analysis). Here we review the current state of glyco-nanotechnology focusing on diagnosis, therapeutics, and analysis of human diseases. We highlight how glyco-nanotechnology could aid in improving diagnostic methods for the detection of disease biomarkers with magnetic resonance imaging (MRI) and fluorescence imaging (FLI), enhance therapeutics such as anti-adhesive treatment of cancer and vaccines against pneumonia, and advance analysis such as the rapid detection of pharmaceutical heparin contaminant and recombinant SARS-COV-2 spike protein. We illustrate these progressions and outline future potentials of glyco-nanotechnology in advancing human health.