Bioelectric Properties Research Articles

Photoperiod and dietary treatment in freshwater modulate the short-term intestinal response to seawater in Atlantic salmon (Salmo salar)

Stimulation and timing of smoltification are essential for successful Atlantic salmon (Salmo salar) aquaculture. This study investigated intestinal responses during dietary and photoperiod manipulation in freshwater (FW) and after a subsequent seven days residence in seawater (SW). “Small” and “large” Atlantic salmon parr (∼40 g and ∼ 130 g respectively) were treated in FW for 12 weeks and thereafter transferred to SW for seven days. During the FW phase, fish underwent two different light conditions, 24 L:0D – 24 L (“LL-LL” groups) and 7 L:17D – 24 L (“SP-LL” groups) or fed with either regular feed (“LL-LL C" and “SP-LL C" groups) or feed enriched with a salt mix plus free tryptophan (“LL-LL + diet” and “SP-LL + diet” groups). We analyzed Na+/K+-ATPase (NKA) activity, tissue bioelectrical properties in Ussing chambers, and intestinal fluid composition. The NKA activity showed minor variations in relation to fish size, treatments, or intestinal region (anterior or posterior). Photoperiod modulated epithelial bioelectrical properties (Isc and Rt) of the anterior and posterior intestine, particularly transepithelial resistance (Rt). Pharmacological experiments, targeting apical Na+/K+/2Cl− (NKCC2) and Na+/Cl− (NCC) co-transporters revealed intestinal region- and water salinity-dependent effects. In addition, stimulation of the intracellular cAMP with forskolin and IBMX showed intestinal region-, water salinity, and treatment-dependence responses with clear functional specialization of the anterior and posterior intestine. The intestinal fluid composition reflected the ability to process ingested SW and showed little variation in large fish. In summary, our data suggest a better pre-adaptation of the intestine during light-stimulated smoltification (SP-LL groups), and the combination of light and diet might give, in an industrial aquaculture setting, an advantage to smaller, but not larger smolts. Intestinal fluid composition in small fish can be used as an index of intestinal function and may act as a long-term performance proxy in SW Atlantic salmon.

P400 Identifying Nutritional targets in Crohn’s disease: INTICO1: a time-limited trial of exclusive enteral nutrition during adult CD remission

Abstract Background During clinical remission in adult Crohn’s disease (CD), impaired health reacted quality of life and fatigue is common, and the nutritional state may be affected by factors such as restrictive eating and altered anatomy from previous inflammation or surgeries. Adults with CD in clinical remission do not routinely undergo nutritional assessments or intervention. The INTICO1 study used a time-limited trial of exclusive enteral nutrition (EEN) to expose and explore nutritionally sensitive aspects of in adults with CD during remission. The extent to which the nutritional state relates to the quality of CD remission and the potential role for nutritional therapies is neither well described nor understood. Methods This was a single arm longitudinal observation study with a dietary intervention. 24 adults in CD remission (Harvey Bradshaw <5, faecal calprotectin <250) underwent assessment of nutritional state at 3 time points; after habitual diet (assessment 1), after 7 days of polymeric EEN (assessment 2) and after a 2-week gradual return to habitual diet (assessment3). Assessments comprised food diary analysis, anthropometry, bio-electrical impedance analysis, routine pathology measures of micronutrient concentration, and patient reported outcome measures (PROMs). Results Assessment 1 (habitual diet) identified individuals with multiple inadequacies of intake (7% (26/368)) micronutrients bloods below the normal laboratory range (see table for analytes) reduced lean mass, low phase angle (PhA) and excessive fatigue (reduced SF-36 vitality). At assessment 2 (post EEN), subjects had fewer deficiencies 4% (16/368), with significant increases seen in Vitamins A, D, E, B2, B6, B9 and the minerals Ca, Cu, Po4 and Se. At visit 3 (return to free diet), micronutrient concentrations reverted toward assessment 1 level, although B6 and B9 remained significantly higher (pairwise comparison visit 1 vs visit 3). BIA measures of nutritional status (PhA) and the SF36 physical function score improved 1 and 2 (5.2 vs 5.4 p<0.01 and 95 v100 p<0.05) and returned to baseline levels on return to free diet (Assessment 3). Conclusion A time-limited trial (7 days) of EEN, given in this setting of adults in CD remission led to changes in micronutrient biochemistry, objective improvement in the bioelectrical properties of the body (increased phase angle) and an improvement in fatigue among the subjects as captured by the SF36-PF. The study suggests that impaired nutritional state and excessive fatigue is likely to be prevalent among adults with CD during remission and may be sensitive to nutritional intervention.

Observation of topological action potentials in engineered tissues

The interface between two tissues can have very different bioelectrical properties compared to either tissue on its own. Here we show that an interface between non-excitable tissues can be electrically excitable because of an interaction between the currents passing through the gap junctions—electrically resistive intercellular connections—and the non-linear current–voltage dependence in the ion channels on either side of the interface. Our theory shows that this topologically robust excitability occurs over a far larger range of ion channel expression levels than can support excitability in the bulk. The corresponding interfacial action potentials can cause local elevations in calcium concentration, possibly providing a bioelectrical mechanism for interface sensing. The observed topological action potentials point to the possibility of other types of topological effect in electrophysiology and at other diffusively coupled interfaces. Interfaces between non-excitable tissues can be electrically excitable, suggesting a possible bioelectrical mechanism for interface sensing.

Body Composition, Somatotype and Raw Bioelectrical Impedance Parameters of Adolescent Elite Tennis Players: Age and Sex Differences

Studies analyzing tennis players' body composition and morphological and bioelectrical characteristics are scarce, especially among adolescents. This study aimed to explore sex- and age-based differences in body composition, somatotype, and bioelectrical properties among elite young male and female tennis players aged 13-16 years. Twenty-two male (14.45 ± 1.10 years) and 20 female (14.30 ± 1.03 years) elite tennis players participated in this study and were compared according to sex (males vs. females) and, within each sex, according to age (13-14 years vs. 15-16 years). Female adolescent elite tennis players had higher body fat (BF) percentage and higher endomorphy than males. They also had lower skeletal muscle mass and total body water (TBW) percentages. Older boys had lower resistance and a higher TBW and phase angle (PhA) than younger boys, likely due to maturation and performance. No significant differences were found between younger and older girls, except for the PhA, potentially associated with better cell function and performance. This study provides valuable reference data for coaches of elite youth tennis players. Due to the few differences found in body composition and somatotype in the different age groups, the PhA may be used by practitioners as a reference for cell function and performance.

Sustainable conversion of antibiotic wastewater using microbial fuel cells: Energy harvesting and resistance mechanism analysis

In this study, tetracycline (TC) can be degraded in microbial fuel cells (MFCs) rapidly and efficiently for the synergistic effect of microbial metabolism and electrical stimulation. Different TC concentrations had different effects on the bioelectric performance of MFCs. Among them, 10 mg/L TC promoted the bioelectric properties of MFCs, the maximum power density reached 1744.4 ± 74.9 mW/cm2. In addition, we demonstrated that Geobacter and Chryseobacterium were the dominant species in the anode biofilm, while Azoarcus and Pseudomonas were the prominent species in the effluent, and the initial TC concentration affected the microbial community composition. Furthermore, the addition of TC increased the relative abundance of aadA3, sul1, adeF, cmlA, and tetC in reactors, indicating that a single antibiotic could promote the expression of self-related resistance as well as the expression of other ARGs. Moreover, the presence of TC can increase the relative content of mobile genetic elements (MGEs) and greatly increase the risk of antibiotic resistance genes (ARGs) spreading. Meanwhile, network analysis revealed that some microorganisms (such as Acidovorax caeni, Geobacter soil, and Pseudomonas thermotolerans) and MGEs may be potential hosts for multiple ARGs.

Electroactive Biomaterials for Facilitating Bone Defect Repair under Pathological Conditions.

Bone degeneration associated with various diseases is increasing due to rapid aging, sedentary lifestyles, and unhealthy diets. Living bone tissue has bioelectric properties critical to bone remodeling, and bone degeneration under various pathological conditions results in significant changes to these bioelectric properties. There is growing interest in utilizing biomimetic electroactive biomaterials that recapitulate the natural electrophysiological microenvironment of healthy bone tissue to promote bone repair. This review first summarizes the etiology of degenerative bone conditions associated with various diseases such as type II diabetes, osteoporosis, periodontitis, osteoarthritis, rheumatoid arthritis, osteomyelitis, and metastatic osteolysis. Next, the diverse array of natural and synthetic electroactive biomaterials with therapeutic potential are discussed. Putative mechanistic pathways by which electroactive biomaterials can mitigate bone degeneration are critically examined, including the enhancement of osteogenesis and angiogenesis, suppression of inflammation and osteoclastogenesis, as well as their anti-bacterial effects. Finally, the limited research on utilization of electroactive biomaterials in the treatment of bone degeneration associated with the aforementioned diseases are examined. Previous studies have mostly focused on using electroactive biomaterials to treat bone traumatic injuries. It is hoped that this review will encourage more research efforts on the use of electroactive biomaterials for treating degenerative bone conditions.

Development of an Imaging and Impedance Flow Cytometer Based on a Constriction Microchannel and Deep Neural Pattern Recognition

This article presents an imaging and impedance flow cytometer based on a constriction microchannel with corresponding cell-type classification based on deep neural pattern recognition. When an incoming cell reached the entrance of the constriction microchannel, the image of the nucleus labeled with fluorescence was captured by a high-speed camera without the concern of losing focus, whereas when the cell deformed through the constriction microchannel by effectively blocking electrical lines, large impedance variations were sampled by an impedance analyzer. Six key biostructural and bioelectrical parameters (e.g., cell diameter, nuclear roundness, and cytoplasmic conductivity) from thousands of single cells were extracted, producing a successful rate of 88.3% in classifying A549 versus Jurkat versus K562 cells based on the feedforward neural network. In addition, multilayer neural networks of deep learning (e.g., VGG16 of CNN and LSTM of RNN) were also used to process fluorescent images and impedance profiles, producing an almost 100% successful rate in cell-type classification. In summary, the microfluidic flow cytometer reported in this article could characterize single-cell biostructural and bioelectrical properties in a high throughput manner, realizing high successful rates of cell-type classification.

Regulation of Porcine Oviduct Epithelium Functions via Progesterone and Estradiol Is Influenced by Cortisol.

Preimplantation maternal stress, characterized by elevated glucocorticoids (GCs), has been linked to reproductive failures caused by impaired oviduct functionality, which is known to be predominantly regulated by the sex steroids, progesterone (P4) and (17)estradiol (E2). Although steroid receptors share analogous structures and binding preferences, the interaction between GCs and E2/P4 in the oviduct has attracted little attention. Using an air-liquid interface culture model, porcine oviduct epithelial cells were stimulated with single (cortisol, E2, P4) or hormone mixtures (cortisol/E2, cortisol/P4) for 12 hours and 72 hours. Cultures were subsequently assessed for epithelial morphometry, bioelectrical properties, and gene expression responses (steroid hormone signaling, oviductal function, immune response, and apoptosis). Results confirmed the suppressive role of P4 in regulating oviduct epithelium characteristics, which was partially opposed by E2. Besides increasing the ratio of ciliated cells, cortisol antagonized the effect of P4 on epithelial polarity and modified sex steroid-induced changes in transepithelial electrical properties. Both sex steroids affected the glucocorticoid receptor expression, while cortisol downregulated the expression of progesterone receptor. The overall gene expression pattern suggests that sex steroid dominates the cotreatment, but cortisol contributes by altering the gene responses to sex steroids. We conclude that besides its individual action, maternal cortisol interplays with sex steroids at phenotypic and molecular levels in the oviduct epithelium, thereby influencing the microenvironment of gametes and early embryos.

Dielectrophoretic characterization of macrophage phenotypes.

Different macrophage phenotypes play important roles in diverse biological processes and diseases. In this study, we have characterized the dielectrophoretic responses of human monocytes and macrophage phenotypes: nonactivated (M0), pro-inflammatory (M1), and pro-healing (M2a). Dielectrophoretic responses of cells change as a function of frequency of the applied electric field. We measured the crossover frequency at which cells transition from negative to positive dielectrophoresis (DEP) or vice versa using interdigitated electrodes. For these characterization experiments, we also developed a new low-conductivity media formulation that retained 100% of the initial viability for 1h. Human THP1 monocytes showed a distinguishable DEP response from mature macrophages. M1 macrophages also showed a distinct DEP response compared to M0 and M2a macrophages. No clear distinction could be drawn between M0 and M2a. The median values of the crossover frequencies of monocytes, M0, M1, and M2a were 38, 21, 11, and 23kHz, respectively. Membrane capacitances of these cells were calculated consequently, and the values were 0.0111, 0.0128, 0.0244, and 0.0117F/m2 for monocytes, M0, M1, and M2a, respectively. These results show how bioelectric properties are influenced by changes in macrophage phenotype.

A Microfluidic Platform for Characterizing Single-Cell Intrinsic Bioelectrical Properties With Large Sample Size

As the golden instrument of blood-cell phenotyping, hematology analyzers still cannot quantify intrinsic bioelectrical parameters of single cells due to limitations in sensitive structures and models. In this article, a microfluidic impedance platform composed of multiple paralleled double T-type constriction microchannels was developed, where raw impedance of traveling cells can be converted into intrinsic bioelectrical parameters of specific membrane capacitance <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${C}_{\textit {sm}}$ </tex-math></inline-formula> , cytoplasmic conductivity <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sigma _{\textit {cy}}$ </tex-math></inline-formula> , and cell diameter <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${D}_{c}$ </tex-math></inline-formula> leveraging the newly developed bioelectrical model. In order to solve the problem of channel blockage, pathways for impedance measurement and cellular passing through were decoupled, and thus the microfluidic platform was capable of characterizing 1906 ± 909 K562 cells/sample ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${n}_{sample} =$ </tex-math></inline-formula> ~50) and 2010 ± 1218 HL-60 cells/sample ( <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${n}_{sample} =$ </tex-math></inline-formula> ~30), effectively meeting the requirements of hematology analyzers (~1000 cells/sample). Based on this microfluidic platform: 1) <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${C}_{\textit {sm}}$ </tex-math></inline-formula> , <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sigma _{\textit {cy}}$ </tex-math></inline-formula> , and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${D}_{c}$ </tex-math></inline-formula> from ~100000 K562 and HL-60 cells were quantified, producing a high successful rate of ~100% in classifying K562 versus HL-60 cells and 2) <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${C}_{\textit {sm}}$ </tex-math></inline-formula> , <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">$\sigma _{\textit {cy}}$ </tex-math></inline-formula> , and <inline-formula xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink"> <tex-math notation="LaTeX">${D}_{c}$ </tex-math></inline-formula> from ~1000 cells of granulocytes, lymphocytes, and monocytes were quantified, producing a high successful rate of ~80% in classifying these three types. In conclusion, the presented microfluidic platform has the potential to be used as an indispensable sensing unit in hematology analyzers in the future.

Core Concept Of Bioelectronic Medicine And Their Theranostic Application In Cancer

Bioelectronic medicine is a way of treating in which the electrical communication networks of the body are altered to treat disease. Bioelectric circuitry in every cell creates a resting membrane potential as well as endogenous electric fields that regulate cell function and communication. The theory that cancer is caused by bioelectrical circuitry malfunctions in cells is now widely acknowledged. This opens up the possibility of using bioelectronic medicine to develop new cancer treatments by influencing the disease's bioelectrical properties. To meet societal and technical obstacles, today's individuals aspire to better their quality of life. So, in the midst of all of this, bioelectronic medicine has altered the way we practice medicine and has proven to dramatically enhance healthcare outcomes. This technique employs a variety of procedures, such as neuromodulation, to treat a specific disease, ailment, or damage. Interfacing electronics with nerves to specifically target the biological processes underlying diseases. In cancer, screening and early detection are crucial for the patient's therapy to be successful and for the patient's survival percentage to grow. For illness diagnosis, therapy, and follow-up, the development of analytical methods for non-invasive detection through the analysis of cancer biomarkers is crucial. Tumor biomarkers are substances or processes that indicate the existence of cancer in the body in clinical situations. These biomarkers can be detected using biosensors, which are popular alternatives to traditional approaches due to their speed, accuracy, and point-of-care applicability. Here we have discussed the consequences of current cancer treatments and bioelectronic medicine a combat for cancer diagnosis and treatment.

Abstract 5382: Biofield therapy suppressed the growth of human pancreatic cancer cells by modulation of cell cycle and cell voltage potentials

Abstract Biofield therapies have gained popularity and are being explored as possible treatments for cancer. In some cases, devices have been developed that mimic the electromagnetic fields (EMF) that are emitted from people delivering biofield therapies. However, it is not clear if EMFs are the mechanism of action. We previously reported that biofield therapy significantly inhibited the growth of lung cancer cells in vitro and their relevant animal model mediated through inflammatory and immune pathways. We expanded this research to examine the effects of human biofield therapy on the growth of pancreatic ductal adenocarcinoma (PDAC) cells and explored relevant mechanisms. Cell viability of human pancreatic cancer Panc-1 and mouse pancreatic cancer Panc02 cells was measured by PrestoBlue assay. Cell cycle was measured by PI staining and cell voltage potentials were assessed using DiBAC4 staining. It is well-established that cancer cells have distinct bioelectrical properties and most have depolarized cell voltage potentials that support cell proliferation. Expression of cell signaling proteins was determined by Western blot. We found that Panc-1 and Panc02 cells exposed to biofield treatment for 15 and 30 mins, respectively, resulted in significantly lower viability compared to that of sham control. These experiments were replicated 12 times for Panc-1 cells and 6 times for Panc02 cells. We further observed that the experimental exposure significantly increased G1 phase population of Panc-1 cells (sham control=43.7% (0.8) vs treatment=55.0% (0.8%), p&amp;lt;0.001). In contrast, Panc02 cells exposed to biofield therapy had significantly higher population of G2/M cells than that of sham control group (sham control=22.5% (0.5) vs treatment=27.7% (1.1), p&amp;lt;0.001). We found that biofield therapy resulted in a 36.7% reduction in cell voltage potentials as measured by the intensity of DiBAC4 staining in Panc-1 cells compared to that of sham controls (p&amp;lt;0.01). Finally, the treatment down-regulated pAkt expression and the pAkt/Akt ratio by 45.3% and 43.8%, respectively, in Panc-1 cells in comparison with the sham control group. The effect of biofield therapy on cell signaling proteins measured by Reverse Phase Proteomic Array in Panc-1 cells and the growth of human Panc-1 mouse orthotopic model is ongoing and the results will be presented at the meeting. Together, these findings suggest that exposure to biofield therapy results in reduced growth of pancreatic cancer cells which might be in part mediated through modification of the cell cycle - differentially for different cell types, reductions in cell voltage potentials suggesting hyperpolarization of cells, and down regulation of PI3K/Akt pathways. Citation Format: Peiying Yang, Sharmistha Chakraborty, Phuong Nguyen, Meng Cui, Andrew Cusimano, Daoyan Wei, Sarah Prinsloo, Lorenzo Cohen. Biofield therapy suppressed the growth of human pancreatic cancer cells by modulation of cell cycle and cell voltage potentials [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 5382.

A computational model of organism development and carcinogenesis resulting from cells’ bioelectric properties and communication

A sound theory of biological organization is clearly missing for a better interpretation of observational results and faster progress in understanding life complexity. The availability of such a theory represents a fundamental progress in explaining both normal and pathological organism development. The present work introduces a computational implementation of some principles of a theory of organism development, namely that the default state of cells is proliferation and motility, and includes the principle of variation and organization by closure of constraints. In the present model, the bioelectric context of cells and tissue is the field responsible for organization, as it regulates cell proliferation and the level of communication driving the system’s evolution. Starting from a depolarized (proliferative) cell, the organism grows to a certain size, limited by the increasingly polarized state after successive proliferation events. The system reaches homeostasis, with a depolarized core (proliferative cells) surrounded by a rim of polarized cells (non-proliferative in this condition). This state is resilient to cell death (random or due to injure) and to limited depolarization (potentially carcinogenic) events. Carcinogenesis is introduced through a localized event (a spot of depolarized cells) or by random depolarization of cells in the tissue, which returns cells to their initial proliferative state. The normalization of the bioelectric condition can reverse this out-of-equilibrium state to a new homeostatic one. This simplified model of embryogenesis, tissue organization and carcinogenesis, based on non-excitable cells’ bioelectric properties, can be made more realistic with the introduction of other components, like biochemical fields and mechanical interactions, which are fundamental for a more faithful representation of reality. However, even a simple model can give insight for new approaches in complex systems and suggest new experimental tests, focused in its predictions and interpreted under a new paradigm.

Direct Effect of Local Cryotherapy on Muscle Stimulation, Pain and Strength in Male Office Workers with Lateral Epicondylitis, Non-Randomized Clinical Trial Study.

Background: Local cryotherapy (LC) is one of the physiotherapeutic methods used in the conservative treatment of lateral epicondylitis (LE). The aim of the study was to verify the direct effect of a single LC procedure on the clinical symptoms of lateral epicondylitis enthesopathy (pain, pain free grip, PFG) and its effect on the bioelectrical properties of the wrist extensor muscles at rest, on maximal contraction and isometric contraction during fatigue. Methods: The study group was 28 men (35.4 ± 6.13 years) with confirmed unilateral epicondylitis. The performed procedures included the assessment of pain (visual analogue scale, VAS), PFG and ARMS (root-mean-square amplitude) and mean frequencies (MNF) of the sEMG signal before (T0) and after (T1) LC on the side with enthesopathy (ECRE) and without enthesopathy (ECRN/E). Results: There was an increase in the ARMS values of the signals recorded during rest and MVC from the ECR muscles both with and without enthesopathy (p = 0.0001, p = 0.006), an increased PFG after LC only on the side with LE (p < 0.0001) and decreased pain (p < 0.0001). During isometric fatigue contraction, a higher ARMS on both the ECRE side (p < 0.0001) and the ECRN/E side (p < 0.0001) was observed after LC treatment, and a lower MNF was observed on both the ECRN/E side (p < 0.0001) and the ECRE side (p < 0.0001) after LC. Conclusions: LC reduces the pain and increases PFG and muscle excitation expressed by ARMS and seems to delay muscle fatigue.

Bioelectricity Buzz.

Bioelectricity Buzz.

Inherent single-cell bioelectrical parameters of thousands of neutrophils, eosinophils and basophils derived from impedance flow cytometry.

Single-cell bioelectrical properties are commonly used for blood cell phenotyping in a label-free manner. However, previously reported inherent single-cell bioelectrical parameters (e.g., diameter Dc , specific membrane capacitance Csm and cytoplasmic conductivity σcy ) of neutrophils, eosinophils and basophils were obtained from only tens of individual cells with limited statistical significance. In this study, granulocytes were separated into neutrophils, eosinophils and basophils based on fluorescent flow cytometry, which were further aspirated through a constriction-microchannel impedance flow cytometry for electrical property characterization. Based on this microfluidic impedance flow cytometry, single-cell values of Dc , Csm and σcy were measured as 10.25 ± 0.66 μm, 2.17 ± 0.30 μF/cm2 , and 0.37 ± 0.05 S/m for neutrophils (ncell =9442); 9.73 ± 0.51 μm, 2.07 ± 0.19 μF/cm2 , and 0.30 ± 0.04 S/m for eosinophils (ncell =2982); 9.75 ± 0.49 μm, 2.06 ± 0.17 μF/cm2 , and 0.31 ± 0.04 S/m for basophils (ncell =5377). Based on these inherent single-cell bioelectrical parameters, neural pattern recognition was conducted, producing classification rates of 80.8% (neutrophil vs. eosinophil), 77.7% (neutrophil vs. basophil) and 59.3% (neutrophil vs. basophil). These results indicate that as inherent single-cell bioelectrical parameters, Dc , Csm and σcy can be used to classify neutrophils from eosinophils or basophils to some extent while they cannot be used to effectively distinguish eosinophils from basophils.

Bioelectric Dysregulation in Cancer Initiation, Promotion, and Progression.

Cancer is primarily a disease of dysregulation – both at the genetic level and at the tissue organization level. One way that tissue organization is dysregulated is by changes in the bioelectric regulation of cell signaling pathways. At the basis of bioelectricity lies the cellular membrane potential or Vmem, an intrinsic property associated with any cell. The bioelectric state of cancer cells is different from that of healthy cells, causing a disruption in the cellular signaling pathways. This disruption or dysregulation affects all three processes of carcinogenesis – initiation, promotion, and progression. Another mechanism that facilitates the homeostasis of cell signaling pathways is the production of extracellular vesicles (EVs) by cells. EVs also play a role in carcinogenesis by mediating cellular communication within the tumor microenvironment (TME). Furthermore, the production and release of EVs is altered in cancer. To this end, the change in cell electrical state and in EV production are responsible for the bioelectric dysregulation which occurs during cancer. This paper reviews the bioelectric dysregulation associated with carcinogenesis, including the TME and metastasis. We also look at the major ion channels associated with cancer and current technologies and tools used to detect and manipulate bioelectric properties of cells.

Inherent bioelectrical parameters of hundreds of thousands of single leukocytes based on impedance flow cytometry.

As label-free biomarkers, bioelectrical properties of single cells have been widely used in hematology analyzers for 3-part differential of leukocytes, in which, however, instrument dependent bioelectrical parameters (e.g., DC/AC impedance values) rather than inherent bioelectrical parameters (e.g., diameter Dc , specific membrane capacitance Csm and cytoplasmic conductivity σcy ) were used, leading to poor comparisons among different instruments. In order to address this issue, this study collected inherent bioelectrical parameters from hundreds of thousands of white blood cells based on a home-developed impedance flow cytometry with corresponding 3-part differential of leukocytes realized. More specifically, leukocytes were separated into three major subtypes of granulocytes, monocytes and lymphocytes based on density gradient centrifugation. Then these separated cells were aspirated through a constriction-microchannel based impedance flow cytometry where inherent bioelectrical parameters of Dc , Csm and σcy were quantified as 9.8 ± 0.7μm, 2.06 ± 0.26 μF/cm2 , and 0.34 ± 0.05 S/m for granulocytes (ncell =134,829); 10.4 ± 1.0μm, 2.45 ± 0.48 μF/cm2 , and 0.42 ± 0.08 S/m for monocytes (ncell =40,226); 8.0 ± 0.5μm, 2.23 ± 0.34 μF/cm2 , and 0.35 ± 0.08 S/m for lymphocytes (ncell =129,193). Based on these inherent bioelectrical parameters, neural pattern recognition was conducted, producing a high "classification accuracy" of 93.5% in classifying these three subtypes of leukocytes. These results indicate that as inherent bioelectrical parameters, Dc , Csm , and σcy can be used to electrically phenotype white blood cells in a label-free manner.

Serum Impedance in Children with Recurrent Respiratory Infections.

The role of disturbed immunoglobulin content during recurrent respiratory tract infections (RTI) might escape recognition in practical children's diagnostics. This study aims to investigate the potential changes in serum impedance caused by a constellation of decreases in the immunoglobulin IgA, IgG, and IgM content in RTI. The control group consisted of children suffering from RTI without any evident decreases in immunoglobulins. Serum bioelectrical properties were measured using impedance spectroscopy and immunoglobulins with an immunoturbidimetric analyzer. We found that the magnitude of serum impedance was significantly smaller in the sick children with immunoglobulin deficiency when compared with those of normal immunoglobulin profile, 134.1±12.8Ω vs 141.2±16.9Ω, respectively. We conclude that serum impedance, a parameter easily measured, has the potential to unravel the immunological underlining of RTI, particularly frequent and troubling infections in children. Screening for immunological disturbance is essential for the prompt implementation of a targeted treatment.

Magnesium–Magnetic Field Synergy Enhances Mouse Bone Marrow Mesenchymal Stem Cell Differentiation into Osteoblasts Via the MAGT1 Channel

Magnesium ion (Mg2+)‐based materials are known to exert osteogenic effects that can be enhanced by the bioelectrical properties of magnetic fields. In this study, we examined the effect of a medium‐strength static magnetic field (SMF), combined with a Mg2+‐containing medium, on the proliferation and osteogenic differentiation of mouse bone marrow mesenchymal stem cells (BMSCs). Mouse BMSCs were divided into a control group, 7.5 mM Mg2+ group, 15 mT SMF group, and 7.5 mM Mg2+ plus 15 mT SMF group. Osteoblast proliferation was measured using a Cell Counting Kit‐8 assay, whereas osteogenic differentiation was detected using alkaline phosphatase (ALP) staining and western blot analysis, respectively. The number and size of calcium nodules were determined using Alizarin Red staining. Compared with those in the control group, the ALP activity, calcium nodule formation, and osteogenic protein expression were promoted in other groups. In particular, Mg2+‐SMF had a significant effect after 7 days of intervention and more effectively promoted BMSC differentiation and proliferation than either Mg2+ or the SMF alone, suggesting that Mg2+‐SMF synergistically contributed to osteogenic differentiation and cell proliferation. To examine their roles in bone differentiation, the Magt1 and Creb1 genes were silenced in BMSCs, and the findings indicated that the synergistic intervention with Mg2+ and magnetic fields might exert osteogenic effects via the MAGT1 channel and CREB1 protein. This study provides an experimental basis for a potential Mg2+‐SMF synergistic artificial bone material that could be clinically applied in the treatment of bone defects.