Pulsed Electromagnetic Field (PEMF) Treatment Ameliorates Murine Model of Collagen-Induced Arthritis.

Rheumatoid arthritis (RA) is an autoimmune disease of the joint synovial membranes. RA is difficult to prevent or treat; however, blocking proinflammatory cytokines is a general therapeutic strategy. Pulsed electromagnetic field (PEMF) is reported to alleviate RA's inflammatory response and is being studied as a non-invasive physical therapy. In this current study, PEMF decreased paw inflammation in a collagen-induced arthritis (CIA) murine model. PEMF treatment at 10 Hz was more effective in ameliorating arthritis than at 75 Hz. In the PEMF-treated CIA group, the gross inflammation score and cartilage destruction were lower than in the untreated CIA group. The CIA group treated with PEMF also showed lower serum levels of IL-1ß but not IL-6, IL-17, or TNF-α. Serum levels of total anti-type II collagen IgG and IgG subclasses (IgG1, IgG2a, and IgG2b) remained unchanged. In contrast, tissue protein levels of IL-1ß, IL-6, TNF-α, receptor activator of nuclear factor kappa-Β (RANK), RANK ligand (RANKL), IL-6 receptor (IL-6R), and TNF-α receptor1 (TNFR1) were all lower in the ankle joints of the PEMF-treated CIA group compared with the CIA group. The results of this study suggest that PEMF treatment can preserve joint morphology cartilage and delay the occurrence of CIA. PEMF has potential as an effective adjuvant therapy that can suppress the progression of RA.

Pulsed Electromagnetic Field (PEMF) Treatment Reduces Lipopolysaccharide-Induced Septic Shock in Mice.

Despite advances in medicine, mortality due to sepsis has not decreased. Pulsed electromagnetic field (PEMF) therapy is emerging as an alternative treatment in many inflammation-related diseases. However, there are few studies on the application of PEMF therapy to sepsis. In the current study, we examined the effect of PEMF therapy on a mouse model of lipopolysaccharide (LPS)-induced septic shock. Mice injected with LPS and treated with PEMF showed higher survival rates compared with the LPS group. The increased survival was correlated with decreased levels of pro-inflammatory cytokine mRNA expression and lower serum nitric oxide levels and nitric oxide synthase 2 mRNA expression in the liver compared with the LPS group. In the PEMF + LPS group, there was less organ damage in the liver, lungs, spleen, and kidneys compared to the LPS group. To identify potential gene targets of PEMF treatment, microarray analysis was performed, and the results showed that 136 genes were up-regulated, and 267 genes were down-regulated in the PEMF + LPS group compared to the LPS group. These results suggest that PEMF treatment can dramatically decrease septic shock through the reduction of pro-inflammatory cytokine gene expression. In a clinical setting, PEMF may provide a beneficial effect for patients with bacteria-induced sepsis and reduce septic shock-induced mortality.

Evaluation of Atopic Dermatitis Improvement Caused by Low-Level, Low-Frequency Pulsed Electromagnetic Fields.

This study aimed to evaluate the effectiveness of using low-level, low-frequency pulsed electromagnetic field (LLLF_PEMF) stimulation to improve atopic dermatitis induced by 2,4-dinitrochlorobenzene (DNCB). Twenty 6-week-old hairless mice were randomly divided into Normal (n = 5), PEMF 15 Hz (n = 5), PEMF 75 Hz (n = 5), and Sham (n = 5) groups. Following the onset of atopic dermatitis symptoms, PEMF groups (15 and 75 Hz) were stimulated with LLLF_PEMF (15 mT) for 8 h per day for 1 week. Sensory evaluation analysis revealed a significant difference between the PEMF 15 Hz group and Sham group (P < 0.05), but these differences were not visually obvious. While both the PEMF and Sham groups had atopic dermatitis lesions, lesion size was significantly smaller in the two PEMF groups than in the Sham group (P < 0.001). Additionally, changes in epithelial thickness because of skin inflammation significantly decreased for both PEMF groups, compared with the Sham group (P < 0.001). In conclusion, these results suggest that PEMF stimulation in vivo triggers electro-chemical reactions that affect immune response. © 2022 Bioelectromagnetics Society.

Sonophoresis with ultrasound-responsive liquid-core nuclei for transdermal drug delivery.

BACKGROUND: Sonophoresis can increase the delivery efficiency of various drugs into the skin. A recent advance in sonophoresis is the use of ultrasound-responsive liquid-core nuclei (URLN) to increase the probability of cavitation. In this study, we developed a URLN and ultrasound device, and demonstrated its effectiveness through in vitro and clinical tests. MATERIALS AND METHODS: Three types of experiments were designed to evaluate the efficiency of sonophoresis with URLN. First, a Franz diffusion cell with cosmetic ingredients was used to analyze quantitatively the amount of drug delivered to the porcine skin. Second, after the application of sonophoresis with URLN, the porcine skin surface was examined using scanning electron microscopy (SEM) to see the changes in morphology. Finally, a clinical test was performed to verify the utility of sonophoresis with URLN. RESULTS: The results indicate that sonophoresis with URLN can increase the amount of compound delivered by approximately 11.9-fold over 6 h for niacinamide and by 7.33-fold over 6 h for adenosine. In addition, we observed approximately 20-30 µm sized pores on porcine skin in SEM images. In clinical testing, the application of sonophoresis with cosmetics containing URLN for 3 min improved the efficiency of transdermal drug delivery by 1.9-fold, the depth of absorption by 2.0-fold, and the speed of absorption by 2.0-fold at 30 min after application. CONCLUSION: We expect that sonophoresis with specialized URLN in transdermal drug delivery could be used widely for various skin-related applications.

Effect of pulsed electromagnetic fields stimulation on ischemic skin model.

This study aimed to evaluate the effect of Pulsed Electromagnetic Fields (PEMF) in improving blood flow reduction and tissue necrosis of ischemic animal induced by skin flap. In each experiment, twenty rats (280-320 g) were randomly divided into control group (n = 10) and PEMF (n = 10) group. All of the rats were performed skin flap in back. In the PEMF group, PEMF (1 Hz, 10 mT) was performed in each experiment. In Experiment-1 (n = 20), PEMF was performed for 90 minutes. In Experiment-2 (n = 20), additionally, a blocking film was inserted, and suture was performed to induce necrosis. PEMF was performed for 30 minutes each day for 7 days. As a result of Speckle-Flow Index (SFI) analysis, in the control group, blood flow continued to decrease immediately after the procedure. In the PEMF group, blood flow was remained constant after 30 minutes and increased after 60 minutes. The blood flow in a specific region substantially increased from the initial state. As a result of skin necrosis analysis, the progression rate in the PEMF group was slower than that of the control group. The rate of necrosis in the PEMF group decreased dramatically from the 6th day, and there was a statistically significant difference between the two groups at the 7th day (p < .05). In this study, it was confirmed that PEMF (1 Hz, 10 mT) has a blood flow improvement and skin tissue necrosis alleviation in the ischemic flap animal model.

Pulsed electromagnetic field potentiates etoposide-induced MCF-7 cell death.

Etoposide is a chemotherapeutic medication used to treat various types of cancer, including breast cancer. It is established that pulsed electromagnetic field (PEMF) therapy can enhance the effects of anti-cancer chemotherapeutic agents. In this study, we investigated whether PEMFs influence the anti-cancer effects of etoposide in MCF-7 cells and determined the signal pathways affected by PEMFs. We observed that co-treatment with etoposide and PEMFs led to a decrease in viable cells compared with cells solely treated with etoposide. PEMFs elevated the etoposide- induced PARP cleavage and caspase-7/9 activation and enhanced the etoposide-induced down-regulation of survivin and up-regulation of Bax. PEMF also increased the etoposideinduced activation of DNA damage-related molecules. In addition, the reactive oxygen species (ROS) level was slightly elevated during etoposide treatment and significantly increased during co-treatment with etoposide and PEMF. Moreover, treatment with ROS scavenger restored the PEMF-induced decrease in cell viability in etoposide-treated MCF-7 cells. These results combined indicate that PEMFs enhance etoposide-induced cell death by increasing ROS induction-DNA damage-caspase-dependent apoptosis. [BMB Reports 2022; 55(3): 148-153].

A Novel Method for Effective Cell Segmentation and Tracking in Phase Contrast Microscopic Images.

Cell migration plays an important role in the identification of various diseases and physiological phenomena in living organisms, such as cancer metastasis, nerve development, immune function, wound healing, and embryo formulation and development. The study of cell migration with a real-time microscope generally takes several hours and involves analysis of the movement characteristics by tracking the positions of cells at each time interval in the images of the observed cells. Morphological analysis considers the shapes of the cells, and a phase contrast microscope is used to observe the shape clearly. Therefore, we developed a segmentation and tracking method to perform a kinetic analysis by considering the morphological transformation of cells. The main features of the algorithm are noise reduction using a block-matching 3D filtering method, k-means clustering to mitigate the halo signal that interferes with cell segmentation, and the detection of cell boundaries via active contours, which is an excellent way to detect boundaries. The reliability of the algorithm developed in this study was verified using a comparison with the manual tracking results. In addition, the segmentation results were compared to our method with unsupervised state-of-the-art methods to verify the proposed segmentation process. As a result of the study, the proposed method had a lower error of less than 40% compared to the conventional active contour method.

Theoretical Design of Lithium Chloride Superionic Conductors for All-Solid-State High-Voltage Lithium-Ion Batteries.

The development of solid electrolytes (SEs) is a promising pathway to improve the energy density and safety of conventional Li-ion batteries. Several lithium chloride SEs, Li3MCl6 (M = Y, Er, In, and Sc), have gained popularity due to their high ionic conductivity, wide electrochemical window, and good chemical stability. This study systematically investigated 17 Li3MCl6 SEs to identify novel and promising lithium chloride SEs. Calculation results revealed that 12 Li3MCl6 (M = Bi, Dy, Er, Ho, In, Lu, Sc, Sm, Tb, Tl, Tm, and Y) were stable phase with a wide electrochemical stability window and excellent chemical stability against cathode materials and moisture. Li-ion transport properties were examined using bond valence site energy (BVSE) and ab initio molecular dynamics (AIMD) calculation. Li3MCl6 showed the lower migration energy barrier in monoclinic structures, while orthorhombic and trigonal structures exhibited higher energy barriers due to the sluggish diffusion along the two-dimensional path based on the BVSE model. AIMD results confirmed the slower ion migration along the 2D path, exhibiting lower ionic diffusivity and higher activation energy in orthorhombic and trigonal structures. For the further increase of ionic conductivity in monoclinic structures, Li-ion vacancy was formed by the substitution of M3+ with Zr4+. Zr-substituted phase (Li2.5M0.5Zr0.5Cl6, M = In, Sc) exhibited up to a fourfold increase in ionic conductivity. This finding suggested that the optimization of Li vacancy in the Li3MCl6 SEs could lead to superionic Li3MCl6 SEs.

Numerical analysis of the change in skin color due to ecchymosis and petechiae generated by cupping: a pilot study.

Cupping is one of the various treatment methods used in traditional oriental medicine. Cupping is also used as a diagnostic method and it may cause skin hyperpigmentation. Quantitative measurements and analysis of changes in skin color due to cupping are critical. The purpose of this study is to suggest an optical technique to visualize and identify changes in skin color due to cupping. We suggest the following analysis methods: digital color spaces [red, green, and blue (RGB) and L∗a∗b], the Erythema Index (E.I.), and the Melanin Index (M.I.). For experiments, we selected and stimulated 10 acupoints at 80 kilopascals (kPa) per minute. The RGB and L∗a∗b color spaces were observed to be decreased (p < 0.05) after cupping. The E.I. and M.I. were observed to be increased significantly (p < 0.05) after cupping. To assess various changes in skin color, we observed the changes for 72 hours. We also obtained the color changes by using the recovery pattern during the recovery period (p < 0.01). We propose that this method can be useful for visual identification and as a way to improve the identification of skin color changes.

Electromagnetic acupuncture to enhance the effects of manual acupuncture on recovery from muscle fatigue of the quadriceps.

The aim of this study was to investigate a new method of manual acupuncture that used a magnetic field to stimulate only one acupoint vertically. We developed an eight-channel electromagnetic acupuncture (EMA) system that uses a solenoid-type electrode to insert the manual acupuncture needle into a hole in an electrode. We used a manual acupuncture needle for magnetic induction in order to penetrate vertically and deeply into tissues. In order to confirm the usefulness of EMA, we investigated the effects of treatment on muscle fatigue after strenuous knee extension/flexion exercises that had been performed by three groups: the nonstimulation, the manual acupuncture, and the EMA groups. Electromyograms showed that the median frequency (MF) in the EMA group had rapidly recovered after 4 minutes (p = 0.608), but that the peak torque had not recovered to the normal state (p < 0.05). Thus, we confirmed that compared with manual acupuncture, EMA resulted in better recovery from muscle fatigue.

Use of pupil size to determine the effect of electromagnetic acupuncture on activation level of the autonomic nervous system.

Magnetic fields are widely considered as a method of treatment to increase the therapeutic effect when applied to acupoints. Hence, this study proposes a new method which creates significant stimulation of acupoints by using weak magnetic fields. We conducted this experiment in order to confirm the effect on the activation level of the autonomic nervous system by measuring pupil sizes in cases of stimulation by using manual acupuncture and electromagnetic acupuncture (EMA) at BL15. We selected 30 Hz of biphasic wave form with 570.1 Gauss. To confirm the biopotential by the magnetic flux density occurring in EMA that affected the activation of the autonomic nervous system, we observed the biopotential induced at the upper and the mid left and right trapezius. We observed a significant decrease in pupil size only in the EMA group (p < 0.05), thus confirming that EMA decreased the pupil size through activation of the parasympathetic nerve in the autonomic nervous system. Moreover, we confirmed that the amplitude of the biopotential which was caused by 570.1 Gauss was higher than ±20 µA. Thus, we can conclude that EMA treatment successfully activates the parasympathetic nerve in the autonomic nervous system by inducing a biotransformation by the induced biopotential.

Development and evaluation of a multi-frequency bioelectrical impedance analysis analyzer for estimating acupoint composition.

The purpose of this study was to suggest a new method of estimating acupoint compositions by using a multi-frequency bioelectrical impedance analysis (MF-BIA) method at 5 kHz, 50 kHz and 200 kHz within 2 cm of acupoints divided into local segments. To verify the system developed, we confirmed the stable occurrence of a constant current at every frequency, regardless of the impedance connected to the electrodes. Moreover, we found left and right distal bicep brachii aponeurosis to be identical by using ultrasound imaging, and we analyzed the repeatability of the findings by making 10 consecutive sets of measurements (p > 0.05). To evaluate the practical use of the acupoint composition, we used the MF-BIA analyzer to measure the left and right LU3, LU4, and LU9 at the lung meridian. We confirmed that the potentials generated were equal to the changes in the cell membrane function, which were caused by the applied frequency (p < 0.01). We also verified that the MF-BIA analyzer measurements corresponded to the acupoint components by comparing the left and right potentials generated (p > 0.05). Hence, we conclude that the MF-BIA analyzer can be used to estimate the acupoint composition based on the acupoint state.

Development and evaluation of a bio-ion measurement system on acupoints for meridian diagnosis.

The aim of this study was to develop a new method of measuring the meridian energy potential (MEP) at an acupoint with bioelectrical impedance in order to establish an objective meridian diagnosis. To confirm the reflection of the changes in body composition at acupoints, the changes in the MEP on the bladder meridian before, during and after cupping were observed. Additionally, to evaluate the usefulness of diagnosis, the MEP on the stomach meridian before and after a meal was measured. Significant increases were found at every acupoint during cupping and after eating a meal. It was confirmed that the MEP data reflected changes in body composition at every acupoint and that these changes were associated with functioning of the associated internal organs. In conclusion, we propose the usefulness of this method, which can indicate the state of acupoints.

Real-time measurement of skin erythema variation by negative compression: pilot study.

Skin erythema has been widely used as a diagnostic parameter in dermatology. This study describes a methodology for real-time measurement of skin erythema variation induced by negative compression. This study developed an optical measurement probe, which includes a RGB color sensor that translates in the vertical direction, with the magnitude of vertical translation dependening on the amount of skin deformation. Real-time measurement of erythema variation as a function of both negative compression and time was performed in vivo on 10 measurement sites located on the back of each of 12 volunteers who participated in this study. Negative compression was sequentially applied from -30 to -80 kPa and continuously at a constant magnitude (-80 kPa) condition. The results showed that skin erythema was uniformly induced at the measurement sites and linearly increased as a function of both negative compression and time. A wide range of individual variation was noted for skin erythema, which may be due to variations in anisotropic skin properties between volunteers. This study demonstrated the clinical feasibility of a novel optical device for skin erythema measurement. Future studies are needed to investigate the clinical applications of this device.

Comparison of 2 methods of non-invasive treatment between transcutaneous electrical stimulation and pulsed electromagnetic field stimulation as replacement of invasive manual acupuncture.

The aim of this study was to find the non-invasive optimal alternative method for Manual Acupuncture. Existing researches had reported that Transcutaneous Electrical Acupoint Stimulation (TEAS) was an effective treatment method instead of manual acupuncture. In place of the TEAS, we suggested the Pulsed Electromagnetic Fields (PEMFs). Thus, we designed the PEMFs system which can stimulate only an acupoint. There have been no researches which reported therapeutic effect when stimulating at an identical acupoint by TEAS and PEMFs. Hence, this study investigated the therapeutic effect on the muscle fatigue after the strenuous knee extension/flexion exercise by two stimulations. We selected the stimulation method of both TEAS and PEMFs by using 2Hz biphasic rectangular wave pulse and pulse width 0.2ms. The magnetic flux was the 30.92mT (309.2gauss) at 2 Hz. The electromyogram (EMG) and the maximal voluntary contraction (MVC) at rectus femoris were measured. The Median Frequency (MF) at TEAS group was significantly effective at 6 minutes (p=0.499). The PEMFs group was recovered to the MF rapidly after 4 minutes (p=0.166). The results of the peak torque indicated that both non-stimulation group and TEAS group did not recover to the peak torque at pre-exercise during the recovery period (p<0.05). In contrast, the significant treatment effect of PEMFs group was found after 14 minutes (p=0.135). The results of this study demonstrated that PEMFs were better than TEAS as a non-invasive method to replace the manual acupuncture.

Electrical characterization of proposed transpositional acupoints on the urinary bladder meridian in a rat model.

Specific electrical characteristicsof acupointswere investigated on the urinary bladder (BL) meridian in 14 rats. BL acupointsand non-acupoints on the back were selected and their electrical voltages were measured by using aSPACsystem.The mean voltages of each point or each line were statistically analyzed by using the ANOVA test.The BL meridian showed voltages higher than those of the reference line (P < .05). Bilateral 1st BL lines presented higher voltages than bilateral 2nd BL lines (P < .05). Most BL acupoints had voltageshigher than those for the corresponding reference points (P < .05). In particular, theright BL16 exhibited the biggest difference from the reference point, followed by the left extra BL point-2, the right BL27, the left BL17, and theleft BL45. Additionally, the distributions of neurofilamentsfor several points were investigated by using immunohistochemistry. There was a trend for the BL acupoints to have larger numbers of neurofilaments than the reference points, and that trend seemed to be directly proportional to the difference in voltage between the points.In conclusion, BL acupoints on the back in ratsexhibited specific electric and histologic characteristics. Therefore, those acupointsmay be utilized to investigate the efficacy of acupuncturewith laboratory animals.

Meridian electrical potential response to acupuncture stimulation between operator and subject.

The human body has a symmetric structure and maintains a physiological balance through the harmony of yin and yang. One of the fundamental principles of acupuncture is that unbalanced or abnormal bioenergetic conditions on the left and right meridians may be restored to a balanced, normal condition by acupuncture therapy. In this study, the electrical potential along the stomach meridian was measured to investigate the bioenergy consensus between the operator and subject during acupuncture stimulation, and the acupuncture response on opposite meridians was investigated by comparing the electric potential on the left and right stomach meridian during stimulation of the left side stomach meridian-36. When meridian electrical potential was simultaneously measured in both the operator and subject, opposite polarities were observed, which might indicate the transfer of bioenergy between operator and subject. In addition, the meridian electrical potentials of the subjects' left and right stomach meridians were also always of opposite polarity and presented three different signal patterns, which might have represented the condition of the associated meridian.

Investigation of electrical responses to acupuncture stimulation: the effect of electrical grounding and insulation conditions.

Acupuncture in Oriental medicine has been widely used as a core therapeutic method due to its minimal side-effects and therapeutic efficacy. However, the electrical response to acupuncture stimulation (ERAS) has not been clearly studied under acupuncture conditions that might affect the efficacy of acupuncture therapy. In this study, the ERAS was objectively investigated by measuring meridian electric potentials (MEPs) when the electrical grounding conditions of the operator and subject were varied, and when the insulation conditions of acupuncture needle were varied. MEPs between Sang-geoheo (ST37) and Ha-geoheo (ST39) of the Stomach Meridian (ST) were measured by stimulating Jok-samni (ST36) with an acupuncture needle. For non-insulated acupuncture stimulation (NIAS), the average MEP peak was 148.6 +/- 20.6 when neither the operator nor the subject were electrically grounded, 23.1 +/- 8.8 when the subject only was electrically grounded, 348 +/- 76.8 when the operator only was electrically grounded, and 19.9 +/- 4.7 when both the operator and the subject were electrically grounded. The MEPs presented various magnitudes and patterns depending on the electrical grounding conditions. The MEP pattern was very similar to that of the charge and discharge of a capacitor. For insulated acupuncture stimulation (IAS), the average MEP peak was 20 +/- 4 in all electrical grounding conditions, which is not a significant electric response for acupuncture stimulation. In terms of electricity, this study verified that acupuncture therapy might be affected by acupuncture conditions such as (1) the electrical grounding condition of the operator and the subject and (2) the insulation condition of the acupuncture needle.

Development and clinical testing of an ultrasonic diagnostic system for functional gastrointestinal disorders.

Functional gastrointestinal disorders (FGIDs) affect millions of people without regard for age, race or sex, but little information related to FGIDs and few methods are available for diagnosing FGIDs. Therefore, the aims of this study were to investigate any alterations to the gastrointestinal tracts induced by FGIDs and to develop and test an ultrasonic diagnostic system capable of detecting the alteration in the gastrointestinal tract. Palpation/percussion examinations were performed on 40 participants with or without FGIDs to identify any mechanical alterations to the gastrointestinal tract induced by FGIDs. An ultrasonic diagnostic system for FGIDs was developed and clinical trials were performed on same participants used in the palpation/percussion examinations to test the system under actual clinical conditions. The results obtained from the palpation/percussion examinations showed that a gastrointestinal tract with a FGID became more rigid than a healthy tract (p < 0.05). Clinical trials also showed that gastrointestinal tracts in the patient group with FGIDs were in fact more rigid than those in the control group without FGIDs (p < 0.05). These findings indicated that our newly designed ultrasonic diagnostic system may be useful in clinics to accurately diagnose FGIDs through detecting mechanical alterations to the rigidity of the gastrointestinal tract induced by FGIDs. The current study may be valuable by identifying for the first time mechanical alterations of the gastrointestinal tract induced by FGIDs and may prove valuable as the first step in the development of a diagnostic system for FGIDs.

Development of acupoints discrimination system using electric properties of acupoints and non-acupoints.

The conventional acupuncture-point stimulus pattern uses direct current (DC) to discriminate acupuncture point and meridian lines, which are fundamental to diagnosis and treatment in Oriental medicine. However, DC is insufficiently reliable in discriminating these acupuncture points and lines. To overcome these problems, the authors extracted optimal parameters (e.g., square-like waveform with a frequency of 3 to approximately 5 kHz) with a single power alternating current (SPAC) stimulus pattern of 1.28V. The SPAC stimulus pattern has little or no effect on cells and the body's physiological state and minimizes polarization and ionization of cells because it uses low voltage and alternating current. The authors developed a new meridian discrimination system that can be used with the SPAC.