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Adipose-derived mesenchymal stem cells (ADMSCs) possess the ability to transform into various cell types, including neurons. It has been proposed that the optimization of this transformation can be achieved by using photobiomodulation (PBM). The objective of this laboratory-based investigation was to induce the transformation of immortalized ADMSCs (iADMSCs) into neurons with chemical triggers and then evaluate the supportive effects of PBM at two different wavelengths, 525 nm and 825 nm, each administered at a dose of 5 J/cm 2 , as well as the combined application of these wavelengths. The results revealed that the treated cells retained their stem cell characteristics, although the cells exposed to the green laser exhibited a reduction in the CD44 marker. Furthermore, early, and late neuronal markers were identified using flow cytometry analysis. The biochemical analysis included the assessment of cell morphology, viability, cell proliferation, potential cytotoxicity, and the generation of reactive oxygen species (ROS). The findings of this study indicate that PBM does not harm the differentiation process and may even enhance it, but it necessitates a longer incubation period in the induction medium. These research findings contribute to the validation of stem cell technology for potential applications in in vivo, pre-clinical, and clinical research environments., (© 2024. The Author(s).)

Background: Radiation therapies are often associated with permanent devitalization in the surrounding tissue. The authors hypothesized that stem cells are damaged depending on each irradiation dose and frequency of fractionated radiotherapies, which results in impaired tissue function, including wound-healing capacity., Methods: Susceptibility of human adipose-derived stem cells (ASCs) to a single irradiation (0 to 10 Gy) was assessed in vitro. In vivo chronic radiation effects were also assessed on mouse dorsal skin ( n = 4 to 5) for 6 months after a total of 40 Gy irradiation (0 Gy as control) using 1 of 3 fractionated protocols (2 Gy daily for 20 days, 10 Gy weekly for 4 weeks, or 10 Gy monthly for 4 months). Oxygen partial pressure, oxygen saturation of hemoglobin, and dorsal skin viscoelasticity were measured periodically, and wound healing and tissue immunohistology were compared at 6 months., Results: A single irradiation of cultured human ASCs resulted in a dose-dependent increase in cell death up to 2 Gy but with no further increases between 2 and 10 Gy. Most of the apoptotic ASCs were in the proliferation phase. Among the 3 in vivo irradiation protocols, the 2 Gy×20 group had the most severe chronic tissue damage (ie, skin dysfunction, subcutaneous atrophy, depletion of CD34 + stem cells) 6 months after the irradiation. Wound healing was also impaired most significantly in the 2 Gy×20 group., Conclusion: These results have important clinical implications for surgeons and radiotherapists in the timing of surgical interventions and the optimization of fractionation protocols., Clinical Relevance Statement: Irradiation damages stem cells depending on the radiation dose and frequency. Using the ultimately optimized protocol, surgeons can minimize the long-term functional deficits of radiated tissue without losing the anticancer efficacy of radiation therapy., (Copyright © 2023 by the American Society of Plastic Surgeons.)

Radiation causes damage to normal tissues that leads to increased oxidative stress, inflammation, and fibrosis, highlighting the need for the selective radioprotection of healthy tissues without hindering radiotherapy effectiveness in cancer. This study shows that adiponectin, an adipokine secreted by adipocytes, protects normal tissues from radiation damage invitro and invivo. Specifically, adiponectin (APN) reduces chronic oxidative stress and fibrosis in irradiated mice. Importantly, APN also conferred no protection from radiation to prostate cancer cells. Adipose tissue is the primary source of circulating endogenous adiponectin. However, this study shows that adipose tissue is sensitive to radiation exposure exhibiting morphological changes and persistent oxidative damage. In addition, radiation results in a significant and chronic reduction in blood APN levels from adipose tissue in mice and human prostate cancer patients exposed to pelvic irradiation. APN levels negatively correlated with bowel toxicity and overall toxicities associated with radiotherapy in prostate cancer patients. Thus, protecting, or modulating APN signaling may improve outcomes for prostate cancer patients undergoing radiotherapy., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)

Photobiomodulation (PBM) is a well-established medical technology that employs diverse light sources like lasers or light-emitting diodes to generate diverse photochemical and photophysical reactions in cells, thereby producing beneficial clinical outcomes. In this study, we introduced an 830 nm near-infrared (NIR) laser irradiation system combined with a microscope objective to precisely and controllably investigate the impact of PBM on the migration and viability of human adipose mesenchymal stem cells (hADSCs). We observed a biphasic dose-response in hADSCs' viability and migration after PBM exposure (0-10 J/cm 2 ), with the 5 J/cm 2 group showing significantly higher cell viability and migration ability than other groups. Additionally, at the optimal dose of 5 J/cm 2 , we used nanoparticle tracking analysis (NTA) and found a 6.25-fold increase in the concentration of extracellular vesicles (EVs) derived from hADSCs (PBM/ADSC-EVs) compared to untreated cells (ADSC-EVs). Both PBM/ADSC-EVs and ADSC-EVs remained the same size, with an average diameter of 56 nm measured by the ExoView R200 system, which falls within the typical size range for exosomes. These findings demonstrate that PBM not only improves the viability and migration of hADSCs but also significantly increases the EV yield., Competing Interests: Declaration of Competing Interest It was declared that no conflicts of interest exist about the publication of this paper., (Copyright © 2024 Elsevier B.V. All rights reserved.)

In recent years exposure of living beings to radiofrequency radiation (RFR) emitted from wireless equipment has increased. In this study, we investigated the effects of 3.5-GHz RFR on hormones that regulate energy metabolism in the body. Twenty-eight rats were divided into four groups: healthy sham (n = 7), healthy RFR (n = 7), diabetic sham (n = 7), and diabetic RFR (n = 7). Over a month, each group spent 2 h/day in a Plexiglas carousel. The rats in the experimental group were exposed to RFR, but the sham groups were not. At the end of the experiment, blood and adipose tissues were collected from euthanized rats. Total antioxidant, total oxidant, hydrogen peroxide, ghrelin, nesfatin-1, and irisin were determined. Insulin expression in pancreatic tissues was examined by immunohistochemical analysis. Whole body specific absorption rate was 37 mW/kg. For the parameters analyzed in blood and fat, the estimated effect size varied within the ranges of 0.215-0.929 and 0.503-0.839, respectively. The blood and adipose nesfatin-1 (p = 0.002), blood and pancreatic insulin are decreased, (p = 0.001), gherelin (p = 0.020), irisin (p = 0.020), and blood glucose (p = 0.040) are increased in healthy and diabetic rats exposed to RFR. While nesfatin-1 are negatively correlated with oxidative stress, hyperglycemia and insulin, ghrelin and irisin are positively correlated with oxidative stress and hyperglycemia. Thus, RFR may have deleterious effects on energy metabolism, particularly in the presence of diabetes., (© 2024 Bioelectromagnetics Society.)

Purpose: Partial breast irradiations with electronic brachytherapy or kilovoltage intraoperative radiotherapy devices such as Axxent or INTRABEAM are becoming more common every day. Breast is mainly composed of glandular and adipose tissues, which are not always clearly disentangled in planning breast CTs. In these cases, breast tissues are replaced with an average soft tissue, or even water. However, at kilovoltage energies, this may lead to large differences in the delivered dose, due to the dominance of photoelectric effect. Therefore, the aim of this work was to study the effect on the dose prescribed in breast with the INTRABEAM device using different soft tissue assignment strategies that would replace the adipose and glandular tissues that constitute the breast in cases where these tissues cannot be adequately distinguished in a CT scan., Methods and Materials: Dose was computed with a Monte Carlo code in five patients with a 3 cm diameter INTRABEAM spherical applicator. Tissues within the breast were assigned following six different strategies: one based on the TG-43 recommendations, representing the whole breast as water of unity density, another one also water-based but with CT derived density, and the other four also based on CT-derived densities, using a single tissue resulting from different mixes of glandular and adipose tissues. These were compared against the reference dose computed in an accurately segmented CT, following TG-186 recommendations. Relative differences and dose ratios between the reference and the other tissue assignment strategies were obtained in three regions of interest inside the breast., Results and Conclusions: Dose planning in water-based tissues was found inaccurate for breast treatment with INTRABEAM, as it would incur in up to 30% under-prescription of dose. If accurate soft tissue assignments in the breast cannot be safely done, a single-tissue composition of 80% adipose and 20% glandular tissue, or even a 100% adipose tissue, would be recommended to avoid dose under-prescription., (Copyright © 2024 American Brachytherapy Society. Published by Elsevier Inc. All rights reserved.)

The effect of near infrared (NIR) laser irradiation on proliferation and osteogenic differentiation of buccal fat pad-derived stem cells and the role of transient receptor potential (TRP) channels was investigated in the current research. After stem cell isolation, a 940 nm laser with 0.1 W, 3 J/cm 2 was used in pulsed and continuous mode for irradiation in 3 sessions once every 48 h. The cells were cultured in the following groups: non-osteogenic differentiation medium/primary medium (PM) and osteogenic medium (OM) groups with laser-irradiated (L +), without irradiation (L -), laser treated + Capsazepine inhibitor (L + Cap), and laser treated + Skf96365 inhibitor (L + Skf). Alizarin Red staining and RT-PCR were used to assess osteogenic differentiation and evaluate RUNX2, Osterix, and ALP gene expression levels. The pulsed setting showed the best viability results (P < 0.05) and was used for osteogenic differentiation evaluations. The results of Alizarin red staining were not statistically different between the four groups. Osterix and ALP expression increased in the (L +) group. This upregulation abrogated in the presence of Capsazepine, TRPV1 inhibitor (L + Cap); however, no significant effect was observed with Skf96365 (L + Skf)., (© 2022. The Author(s), under exclusive licence to Springer-Verlag London Ltd., part of Springer Nature.)

Photobiomodulation therapy (PBMT) has become an adjuvant therapeutic possibility in body remodeling procedures. Given this scenario, this study was proposed with the aim of evaluating the effects of PBMT to Light Emitting Diode (LED) associating the red (630 nm) and infrared (850 nm) wavelengths in the subcutaneous fatty tissue. This controlled study of comparative intervention that evaluated a sample of subcutaneous fatty tissue from women with grade II obesity. The participants received the LED PBMT treatment with associated red and infrared wavelengths sequentially on the left side of the abdomen and the right side was considered as control, with the collection of biological material performed at the time of bariatric surgery. For histological and immunohistochemical evaluation, Caspase 3, Cleaved Caspase 3, CD68+, HSL and adipophilin markers were used. The participants showed positivity in the expression of Caspase 3 and Cleaved Caspase (p < .0001), CD68+ macrophages (p < .0001), HSL (p < .0001) and adipophilin (p < .0013) in the intervention sample when compared to the control. PBMT and LED associating red and infrared wavelengths were able to promote autophagic lipolysis induced by adipocyte cell apoptosis in the subcutaneous tissue of obese individuals.

Background: Unwanted submental fat (SMF) is aesthetically unappealing, but methods of reduction are either invasive or lack evidence of their use., Objective: The authors sought to evaluate the safety and efficacy of a novel triple-layer high-intensity focused ultrasound (HIFU) regimen for SMF reduction., Methods: Forty Korean subjects with moderate/severe SMF were evaluated after receiving a session of triple-layer HIFU treatments (using 3.0-, 4.5-, and 6.0-mm focusing transducers). The objective evaluation based on the 5-point Clinician-Reported Submental Fat Rating Scale (CR-SMFRS) and patients' satisfaction based on the 7-point Subject Self-Rating Scale (SSRS) were determined 8 weeks after treatment. Three-dimensional image analysis was also performed., Results: At the follow-up visit, the proportion of treatment responders defined as subjects with ≥1-point improvement in CR-SMFRS was 62.5%, and the proportion of patients satisfied with appearance of their face and chin (score ≥4 on the SSRS) was 67.5% of the total patients. The results of 3-dimensional analysis were consistent with clinical observations. Only mild and transient side effects were observed for some patients with no serious adverse effects., Conclusion: The triple-layer HIFU regimen including the novel 6.0-mm transducer has benefits for tightening and rejuvenation of the area with unwanted SMF, showing reasonable safety profiles., (Copyright © 2021 by the American Society for Dermatologic Surgery, Inc. Published by Wolters Kluwer Health, Inc. All rights reserved.)

BACKGROUNDChildhood cancer survivors who received abdominal radiotherapy (RT) or total body irradiation (TBI) are at increased risk for cardiometabolic disease, but the underlying mechanisms are unknown. We hypothesize that RT-induced adipose tissue dysfunction contributes to the development of cardiometabolic disease in the expanding population of childhood cancer survivors.METHODSWe performed clinical metabolic profiling of adult childhood cancer survivors previously exposed to TBI, abdominal RT, or chemotherapy alone, alongside a group of healthy controls. Study participants underwent abdominal s.c. adipose biopsies to obtain tissue for bulk RNA sequencing. Transcriptional signatures were analyzed using pathway and network analyses and cellular deconvolution.RESULTSIrradiated adipose tissue is characterized by a gene expression signature indicative of a complex macrophage expansion. This signature includes activation of the TREM2-TYROBP network, a pathway described in diseases of chronic tissue injury. Radiation exposure of adipose is further associated with dysregulated adipokine secretion, specifically a decrease in insulin-sensitizing adiponectin and an increase in insulin resistance-promoting plasminogen activator inhibitor-1. Accordingly, survivors exhibiting these changes have early signs of clinical metabolic derangement, such as increased fasting glucose and hemoglobin A1c.CONCLUSIONChildhood cancer survivors exposed to abdominal RT or TBI during treatment exhibit signs of chronic s.c. adipose tissue dysfunction, manifested as dysregulated adipokine secretion that may negatively impact their systemic metabolic health.FUNDINGThis study was supported by Rockefeller University Hospital; National Institute of General Medical Sciences (T32GM007739); National Center for Advancing Translational Sciences (UL1 TR001866); National Cancer Institute (P30CA008748); American Cancer Society (133831-CSDG-19-117-01-CPHPS); American Diabetes Association (1-17-ACE-17); and an anonymous donor (MSKCC).

The epidermal-dermal (ED) and dermal-subcutaneous (DS) junctions are the most prominent skin interfaces, which are known to be of primary importance in different dermatological and aesthetic conditions. These interfaces are strongly modified in aging skin, and their effective targeting can lead to improvement of skin appearance in aging and by cellulite. Application of radiofrequency (RF) currents to the skin can selectively produce mechanical stress on these interfaces. Here, we assess the stresses induced by RF currents of different frequencies on EDJ and DSJ and discuss possible applications of the interfacial therapy in aesthetic medicine., Competing Interests: ILK is the managing partner of Wellcomet GmbH. Wellcomet GmbH provided support in the form of salaries for ILK, but did not have any additional role in decision to publish or preparation of the manuscript. The commercial affiliation of ILK with Wellcomet GmbH does not alter the adherence to all journal policies on sharing data and materials., (Copyright © 2021 Ilja L. Kruglikov.)

In this study, we designed a low-power visible ray (V) drive module based on a light-emitting diode (LED) to initiate fat reduction using light source irradiation. A chemical phantom of muscle and fat was fabricated, and the performance of the proposed LED drive module was tested using this chemical phantom. The LED light source could reduce fat by irradiating the skin 4-5 cm deep. The device exhibits a negative feedback and parallel amplification to maintain a stable circuit based on low-power consumption. Muscles have a high-water content and low impedance, whereas fats have a low water content and significant salt content. Therefore, fat exhibits high impedance. Chemical phantoms were fabricated according to these impedance values, and the fat reduction effect using the LED circuits was analyzed. When the fat phantom was irradiated by the light source, the fat impedance lowered, and we confirmed that fat reduction could be obtained. This study is expected to be applicable to family medicine and weight management health care., Competing Interests: The authors declare no conflicts of interest., (Copyright © 2021 Ki-Cheol Yoon and Kwang Gi Kim.)

Hyperthermia technique has received much attention over the last decade being less invasive among the others. Laser therapy is among the most commonly investigated types of ablative hyperthermia for treatment of cancer. In this method an external heat source provided by a laser fiber leads the cancerous tissue to the necrosis stage. For its simulation a cylindrical geometry of a breast tissue containing a tumor is acted upon by a Gaussian form of laser radiation. Then the feasibility of a fat layer injection around the tumor during the therapy is investigated numerically. In order to consider the finite speed of heat transfer, dual phase lag (DPL) model is implemented for prediction of the thermal results. The therapy is addressed with and without the presence of a fat layer around the breast tumor. Results show that the temperature in the tumor increases up to 15 % by the injection of a fat layer. Also, the presence of a fat layer around the tumor shows that the irreversible ablation happens at a faster rate., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Biomedical use of radiation is utilized in effective diagnostic and treatment tools, yet can introduce risks to healthy tissues. High energy photons used for diagnostic purposes have high penetration depth and can discriminate multiple tissues based on attenuation properties of different materials. Likewise, the ability to deposit energy at various targets within tumors make the use of photons effective treatment for cancer. Radiation focused on a tumor will deposit energy when it interacts with a biological structure (e.g. DNA), which will result in cell kill should repair capacity of the tissue be overwhelmed. Likewise, damage to normal, non-cancerous tissues is a consequence of radiation that can lead to acute or late, chronic toxicity profiles. Adipose derived stem cells (ADSCs) are mesenchymal stem cells that have been proven to have similar characteristics to bone marrow derived stem cells, except that they are much easier to obtain. Within the body, ADSCs act as immunomodulators and assist with the maintenance and repair of tissues. They have been shown to have excellent differentiation capability, making them an extremely viable option for stem cell therapies and regenerative medicine applications. Due to the tissue ADSCs are derived from, they are highly likely to be affected by radiation therapy, especially when treating tumors localized to structures with relatively high ADSC content (eg., breast cancer). For this reason, the purpose behind this research is to better understand how ADSCs are affected by doses of radiation comparable to a single fraction of radiation therapy. We also measured the response of ADSCs to exposure at different dose rates to determine if there is a significant difference in the response of ADSCs to radiation therapy relevant doses of ionizing radiation. Our findings indicate that ADSCs exposed to Cesium (Cs 137)-gamma rays at a moderate dose of 2Gy and either a low dose rate (1.40Gy/min) or a high dose rate (7.31Gy/min) slow proliferation rate, and with cell cycle arrest in some populations. These responses ADSCs were not as marked as previously measured in other stem cell types. In addition, our results indicate that differences in dose rate in the Gy/min range typically utilized in small animal or cell irradiation platforms have a minimal effect on the function of ADSCs. The potential ADSCs have in the space of regenerative medicine makes them an ideal candidate for study with ionizing radiation, as they are one of the main cell types to promote tissue healing., Competing Interests: The authors have declared that no competing interests exist.

Obesity, a growing health concern, is associated with an increased risk of morbidity and mortality. Chronic low-grade inflammation is implicated in obesity-driven metabolic complications. Peripheral focused ultrasound stimulation (pFUS) is an emerging non-invasive technology that modulates inflammation. Here, we reasoned that focused ultrasound stimulation of the liver may alleviate obesity-related inflammation and other comorbidities. After 8 weeks on a high-fat high-carbohydrate "Western" diet, C57BL/6J mice were subjected to either sham stimulation or focused ultrasound stimulation at the porta hepatis. Daily liver-focused ultrasound stimulation for 8 weeks significantly decreased body weight, circulating lipids and mitigated dysregulation of adipokines. In addition, liver-focused ultrasound stimulation significantly reduced hepatic cytokine levels and leukocyte infiltration. Our findings demonstrate the efficacy of hepatic focused ultrasound for alleviating obesity and obesity-associated complications in mice. These findings suggest a previously unrecognized potential of hepatic focused ultrasound as a possible novel noninvasive approach in the context of obesity.

The circadian clock exerts temporal coordination of metabolic pathways. Clock disruption is intimately linked with the development of obesity and insulin resistance, and our previous studies found that the essential clock transcription activator, Brain and Muscle Arnt-like 1 (Bmal1), is a key regulator of adipogenesis. However, the metabolic consequences of chronic shiftwork on adipose tissues have not been clearly defined. Here, using an environmental lighting-induced clock disruption that mimics rotating shiftwork schedule, we show that chronic clock dysregulation for 6 months in mice resulted in striking adipocyte hypertrophy with adipose tissue inflammation and fibrosis. Both visceral and subcutaneous depots display enlarged adipocyte with prominent crown-like structures indicative of macrophage infiltration together with evidence of extracellular matrix remodeling. Global transcriptomic analyses of these fat depots revealed that shiftwork resulted in up-regulations of inflammatory, adipogenic and angiogenic pathways with disruption of normal time-of-the-day-dependent regulation. These changes in adipose tissues are associated with impaired insulin signaling in mice subjected to shiftwork, together with suppression of the mTOR signaling pathway. Taken together, our study identified the significant adipose depot dysfunctions induced by chronic shiftwork regimen that may underlie the link between circadian misalignment and insulin resistance., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Objective: in the experiment, to investigate the effect of Quercetin on the NO-dependent reactions of isolated vessels involving endothelium and perivascular adipose tissue (PVAT) after a single X-ray irradiation of rats at a sublethal dose. In a clinical study, to investigate the effect of long-term use of Quercetin on the functional state of themicrovascular endothelium in the elderly patients with metabolic syndrome (MS)., Material and Methods: Experimental studies were performed on vascular fragments obtained from adult male rats(7-8 months) of the control group, in animals exposed to a single R-irradiation at a dose of 7 Gy and animals irradiated in the same dose, which received Quercetin orally for 14 days three times a week based on 10 mg/kg bodyweight. Fragments of the thoracic aorta (TA) and mesenteric artery (MA) were cleaned of perivascular adipose tissue (PVAT-) or left uncleaned (PVAT+), and then were cut into rings (up to 2 mm). The amplitude of the contractionof the rings TA and MA under the influence of phenylephrine (PE, 3 x 10-6 M), the amplitude of the contraction of therings TA and MA in the presence of a competitive blocker of NO-synthase methyl ester of N-nitro-L-arginine(L-NAME, 10-5 M), the amplitude of relaxation of the rings TA and MA in the presence of N-acetylcysteine (NAC, 10-4 M)were measured. The clinical study examined 110 patients with MS criteria in accordance with ATP III (2001).Patients in the main group for 3 months received Quercetin from the same manufacturer, 80 mg three times a day,patients in the control group received placebo., Results: Single R-irradiation disrupts the regulation of the contractile function of TA and MA, which is evidenced bychanges in the contractile reactions of isolated fragments of these vessels as a response to the action of vasoactivecompounds. Course use of Quercetin in irradiated rats leads to the normalization of contractile and dilatory vascular responses due to partial correction of NO metabolism in the endothelium and PVAT. For the majority of patients(69 %) who received Quercetin, a post-occlusive hyperemia test showed a statistically significant increase of maximal volumetric velocity of the skin blood flow rate and duration of the recovery period to the baseline, which indicates about improvement of vasomotor vascular endothelial function., Conclusions: Course use of Quercetin improves the functional state of the microvascular endothelium among theelderly people with MS, normalizes contractile and dilatory vascular responses in irradiated rats due to partial correction of NO metabolism in the endothelium and PVAT., (O. V. Korkushko, E. M. Gorban, O. V. Bondarenko, I. A. Antonyuk-Shcheglova, S. S. Naskalova, O. V. Parshykov, N. O. Utko, A. V. Gavalko, V. B. Shatilo, G. V. Duzhak.)

To investigate the effect of low-intensity pulsed ultrasound (LIPUS) on the proliferation of human adipose-derived mesenchymal stromal cells (hASCs) and uncovered its stimulation mechanism. LIPUS at 30 mW/cm 2 was applied for 5 min/day to promote the proliferation of hASCs. Flow cytometry was used to study the cell surface markers, cell cycle, and apoptosis of hASCs. The proliferation of hASCs was detected by cell counting kit-8, cell cycle assay, and RT-PCR. The expression of hASCs cytokines was determined by ELISA. The differences between transcriptional genes and metabolites were analyzed by transcript analysis and metabolomic profiling experiments. The number of cells increased after LIPUS stimulation, but there was no significant difference in cell surface markers. The results of flow cytometry, RT-PCR, and ELISA after LIPUS was administered showed that the G 1 and S phases of the cell cycle were prolonged. The expression of cell proliferation related genes (CyclinD1 and c-myc) and the paracrine function related gene (SDF-1α) were up-regulated. The expression of cytokines was increased, while the apoptosis rate was decreased. The results of transcriptome experiments showed that there were significant differences in 27 genes;15 genes were up-regulated, while 12 genes were down-regulated. The results of metabolomics experiments showed significant differences in 30 metabolites; 7 metabolites were up-regulated, and 23 metabolites were down-regulated. LIPUS at 30 mW/cm 2 intensity can promote the proliferation of hASCs cells in an undifferentiating state, and the stem-cell property of hASCs was maintained. CyclinD1 gene, c-myc gene, and various genes of transcription and products of metabolism play an essential role in cell proliferation. This study provides an important experimental and theoretical basis for the clinical application of LIPUS in promoting the proliferation of hASCs cells.

Background: In recent decades, low-level laser therapy (LLLT) has occupied a prominent position and has been studied in various fields of knowledge, and your effects have been widely observed in studies about numerous tissues, such as tendons, peripheral nerves, cutaneous tissue, bone, and muscle, in different fields of knowledge., Purpose: To analyze the power transmitted by low-level laser therapy (LLLT) to different tissue samples by using distinct wavelengths., Methods: Skin samples of rat (n = 7, 1.17-1.63 mm) and pig (n = 10; 1.20-2.30 mm); pig fat (n = 10; 2.71-14.01 mm) and pig muscle (n = 10; 1.91-8.91 mm) were analyzed and interposed between the emitter and the power analyzer sensor. All the samples were irradiated sequentially three times, at five equidistant points and average power levels of 35.34(±1.03), 32.40(±0.70), and 42.32(±0.82) mW, for the wavelengths 660, 830, and 904 nm, respectively. Transmitted radiation was measured with a power analyzer connected to a laser emitter. Statistical analysis was performed with a Shapiro-Wilk test followed by ANOVA with Tukey's post hoc test, with a significance level of 5%., Results: The transmitted power of LLLT on skin, fat, and muscle of tissues decreases with the increase of thicknesses, presenting minor attenuation on rat skin, pig fat, and pig muscle for 904 nm. The pig skin has the slight attenuation for 830 nm., Conclusion: The LLLT should be applied after considering the transmission loss taking place in different anatomical structures, following the Beer-Lambert law and attenuation coefficient presented for more practical application in many fields., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflict of interest., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Although low-intensity pulsed ultrasound has been reported to be potential cartilage regeneration, there still unresolved treatment due to cartilage fibrosis and degeneration by a lack of rapid and high-efficiency treatment. The purpose of this study was to investigate the effect of a combination therapy of focused acoustic force and stem cells at site for fast and efficient healing on cartilage regeneration., Methods: Using a rat articular cartilage defects model, one million adipose tissue-derived stem cells (ASCs) were injected into the defect site, and low-intensity focused ultrasound (LOFUS) in the range of 100-600 mV was used for 20 min/day for 2 weeks. All experimental groups were sacrificed after 4 weeks in total. The gross appearance score and hematoxylin and eosin (H&E), Alcian blue, and Safranin O staining were used for measuring the chondrogenic potential. The cartilage characteristics were observed, and type II collagen, Sox 9, aggrecan, and type X collagen were stained with immunofluorescence. The results of the comprehensive analysis were calculated using the Mankin scoring method., Results: The gross appearance scores of regenerated cartilage and chondrocyte-like cells in H&E images were higher in LOFUS-treated groups compared to those in negative control or ASC-treated groups. Safranin O and Alcian blue staining demonstrated that the 100 and 300 mV LOFUS groups showed greater synthesis of glycosaminoglycan and proteoglycan. The ASC + LOFUS 300 mV group showed positive regulation of type II collagen, Sox 9 and aggrecan and negative regulation of type X collagen, which indicated the occurrence of cartilage regeneration based on the Mankin score result., Conclusion: The combination therapy, which involved treatment with ASC and 300 mV LOFUS, quickly and effectively reduced articular cartilage defects.

This work proposes using artificial neural networks (ANNs) for the regression of the dosimetric quantities employed in mammography. The data were generated by Monte Carlo (MC) simulations using a modified and validated version of the PENELOPE (v. 2014) + penEasy (v. 2015) code. A breast model of a homogeneous mixture of adipose and glandular tissue was adopted. The ANNs were constructed using the Keras and scikit-learn libraries for mean glandular dose (MGD) and air kerma (K air ) regressions, respectively. In total, seven parameters were considered, including the incident photon energies (from 8.25 to 48.75 keV), breast geometry, breast glandularity and K air acquisition geometry. Two ensembles of five ANNs each were formed to calculate MGD and K air . The normalized glandular dose coefficients (DgN) were calculated using the ratio of the ensemble outputs for MGD and K air . Polyenergetic DgN values were calculated by weighting monoenergetic values by the spectrum bin probabilities. The results indicate a very good ANN prediction performance when compared to the validation data, with median errors on the order of the average simulation uncertainties (≈ 0.2%). Moreover, the predicted DgN values are in good agreement compared with previously published works, with mean (maximum) differences up to 2.2% (9.4%). Therefore, it is shown that ANNs could be a complementary or alternative technique to tables, parametric equations and polynomial fits to estimate DgN values obtained via MC simulations.

We analyzed the main properties of autologous adipose-derived stromal vascular fraction (SVF) used for the treatment of radiation-induced lesions in the rectum. No statistically significant correlation between the main characteristics of the cell product (cell number, viability) and patient's age or donor area were revealed. The stages and peculiarities of histological changes in the regenerating tissue after injection of autologous adipose tissue cells were analyzed. Morphological changes at the stages of granulation, early and complete epithelialization, and tissue maturation were described.

Cold stimuli and the subsequent activation of β-adrenergic receptor (β-AR) potently stimulate adipose tissue thermogenesis and increase whole-body energy expenditure. However, systemic activation of the β3-AR pathway inevitably increases blood pressure, a significant risk factor for cardiovascular disease, and, thus, limits its application for the treatment of obesity. To activate fat thermogenesis under tight spatiotemporal control without external stimuli, here, we report an implantable wireless optogenetic device that bypasses the β-AR pathway and triggers Ca 2+ cycling selectively in adipocytes. The wireless optogenetics stimulation in the subcutaneous adipose tissue potently activates Ca 2+ cycling fat thermogenesis and increases whole-body energy expenditure without cold stimuli. Significantly, the light-induced fat thermogenesis was sufficient to protect mice from diet-induced body-weight gain. The present study provides the first proof-of-concept that fat-specific cold mimetics via activating non-canonical thermogenesis protect against obesity.

Objectives: Mesenchymal stromal cells (MSC) in bone marrow have been shown to be radioresistant, which is related to pronounced DNA repair mechanisms. Intraoperative radiotherapy (IORT) during breast-conserving surgery for early breast cancer is an innovative technique applying low energy x‑ray to the tumor bed immediately after removal of the tumor. IORT is considered to reduce the risk of local tumor recurrence by directly targeting cells of the tumor bed and altering the local microenvironment. Aim of this study was to investigate whether IORT affects the outgrowth potential of breast adipose tissue-derived MSC (bASC) as part of the tumor bed., Materials and Methods: After surgical tumor resection, biopsies of the tumor bed were taken before (pre IORT) and after IORT (post IORT) and processed applying well-established protocols for ASC isolation and characterization., Results: In all, 95% of pre IORT tumor bed samples yielded persistently outgrowing bASC with typical ASC characteristics: fibroblastoid morphology, proliferation, adipogenic and osteogenic differentiation and ASC surface marker expression. However, none of the post IORT samples yielded persistent outgrowth of bASC., Conclusions: After breast-conserving surgery, approximately 90% of local recurrences emerge in close proximity to the initial tumor bed, potentially reflecting a significant contribution of the tumor bed to relapse. Our data show that IORT, besides the proven effect on breast cancer cells, efficiently modifies the tumor environment by having an impact on tumor bed bASC. This effect on tumor bed stromal cells might contribute to reduce the risk of tumor relapse and metastases.

Advanced cancer patients exhibit cachexia, a condition characterized by a significant reduction in the body weight predominantly from loss of skeletal muscle and adipose tissue. Cachexia is one of the major causes of morbidity and mortality in cancer patients. Decreased food intake and multi-organ energy imbalance in cancer patients worsen the cachexia syndrome. Cachectic cancer patients have a low tolerance for chemo- and radiation therapies and also have a reduced quality of life. The presence of tumors and the current treatment options for cancer further exacerbate the cachexia condition, which remains an unmet medical need. The onset of cachexia involves crosstalk between different organs leading to muscle wasting. Recent advancements in understanding the molecular mechanisms of skeletal muscle atrophy/hypertrophy and adipose tissue wasting/browning provide a platform for the development of new targeted therapies. Therefore, a better understanding of this multifactorial disorder will help to improve the quality of life of cachectic patients. In this review, we summarize the metabolic mediators of cachexia, their molecular functions, affected organs especially with respect to muscle atrophy and adipose browning and then discuss advanced therapeutic approaches to cancer cachexia., Competing Interests: Declaration of competing interest SKB is one of the co-founders of Sanguine Diagnostics and Therapeutics, Inc. The other authors declare no competing interests. The authors have declared that the submitted manuscript is original, is not under consideration by another journal, and has not been published previously in any form. Every author is aware of and has agreed to the content of this paper., (Copyright © 2020. Published by Elsevier B.V.)

Purpose: Diabetes mellitus is a delayed effect of radiation exposure in human and nonhuman primates. Diabetes mellitus is characterized by peripheral tissue insulin resistance, and as a result, irradiation exposure may cause important changes in insulin-sensitive tissues such as muscle and adipose., Methods and Materials: We prospectively investigated changes in response to irradiation (4 Gy whole body exposure) in 16 male rhesus macaques. We evaluated changes in body composition and glycemic control for 2 years. Insulin responsiveness, lipolysis, inflammation, and fibrosis were evaluated at study end., Results: Irradiated animals accumulate less fat and significantly increased percent glycation of hemoglobin A1c over time, such that 40% of irradiated monkeys had values that define them as diabetic at 2 years. Subcutaneous (SQ) adipose tissue was insulin resistant, as evidenced by reduced phosphorylation of the insulin receptor substrate-1 in response to insulin challenge and had increased basal lipolysis despite comparable insulin exposures to control animals. Irradiated SQ adipose tissue had more macrophage infiltration and adipocytes were larger. The observed hypertrophy was associated with decreased glycemic control and macrophage infiltration correlated with decreased adiponectin, signifying that inflammation is associated with worsening health. No evidence of SQ adipose fibrosis was detected., Conclusions: Our study is the first to prospectively illustrate that sublethal irradiation exposures directly propagate metabolic disease in the absence of obesity in nonhuman primates and implicate SQ adipose dysfunction as a target tissue., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Excessive circulating free fatty acids (FFA) cause insulin resistance in peripheral tissues by inhibiting the proximal insulin signaling pathway. White adipose tissue (WAT) is a primary source of FFA generation and release through triglyceride (TG) hydrolysis. Thus, reducing excessive lipolysis in adipocytes ameliorates whole-body insulin resistance in type 2 diabetes. Here, we found that a noninvasive photobiomodulation therapy (PBMT), decreased FFA generation and release in WATs from high-fat diet (HFD)-fed mice and diabetic db/db mice. Meanwhile, plasma FFA and TG levels were reduced in two mouse models after PBMT. PBMT promoted mitochondrial reactive oxygen species (ROS) generation, which inhibited phosphatase and tensin homologue (PTEN) and promoted protein kinase B (AKT) activation. Photoactivation of AKT inhibited the transcriptional activity of Forkhead box transcription factor O1 (FoxO1), reducing expression of lipolytic enzymes and FFA generation and release. Eliminating ROS elimination or inhibiting AKT blocked the effects of the laser therapy in vivo and in vitro. Taken together, PBMT suppresses FFA generation and release in insulin-resistant adipocytes, contributing to improvement of insulin resistance in mouse models of type 2 diabetes., (Copyright © 2019. Published by Elsevier Inc.)

Background: Abdominal adiposity is a cardiovascular risk factor; it is assumed that the combination of radiofrequency and physical exercise may decrease this excess of adipose tissue., Purpose: To understand whether an aerobic physical exercise session associated with abdominal radiofrequency increases the level of lipolytic activity., Methodology: The study analyzes the effect of a combined aerobic exercise session with radiofrequency. Participants were 30 healthy female volunteers, aged 18-28 years, randomly assigned to an experimental group and placebo group. They were characterized by a sociodemographic questionnaire, the International Physical Activity Questionnaire and the Food Frequency Questionnaire. The groups performed an abdominal radiofrequency session followed by moderate aerobic exercise, assessing glycerol concentration and lipid profile values before and after the intervention. In the experimental group, a percentage of potency was used that allowed to maintain the temperature between 40º C and 42º C to the epidermis. In the placebo group, the power of the radiofrequency was 0 Watt. To compare results, Student's t test was used for a significance level of 0.05., Results: There were no significant changes in glycerol concentrations between groups (P > 0.05). There were no changes in the lipid profile of both groups after the intervention (P > 0.05)., Conclusion: The association of exercise with radiofrequency did not present an increased effect on lipolytic activity when compared to the isolated exercise. The application of this technique is a safe intervention., (© 2019 Wiley Periodicals, Inc.)

Ultrasound irradiation makes it possible to generate alternating electric polarization through the electromechanical coupling of materials. It follows that electromagnetic fields are often emitted to the surrounding environment when materials are acoustically stimulated. We investigate the acoustically stimulated electromagnetic (ASEM) response of soft biological tissues. The ASEM signal is detected through a capacitive resonant antenna tuned to the MHz frequency of the irradiated ultrasound waves. The signal is well explained by the stress-induced polarization, which responds linearly to the applied acoustic stress. Induced polarization is clearly observed in the Achilles tendon, aortic wall, and aortic valve samples, whereas it is small in adipose tissue and myocardium samples, indicating that fibrous tissues exhibit electromechanical coupling.

(1) Background: Emerging interest of physicians to use adipose-derived stem cells (ADSCs) for regenerative therapies and the fact that low-dose irradiation (LD-IR ≤ 0.1 Gy) has been reported to enhance the proliferation of several human normal and bone-marrow stem cells, but not that of tumor cells, lead to the idea of improving stem cell therapies via low-dose radiation. Therefore, the aim of this study was to investigate unwanted side effects, as well as proliferation-stimulating mechanisms of LD-IR on ADSCs. (2) Methods: To avoid donor specific effects, ADSCs isolated from mamma reductions of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival assay was used to classify the long-term effects of low-dose radiation in ADSCs. Afterwards, cytotoxicity and genotoxicity, as well as the effect of irradiation on proliferation of ADSCs were investigated. (3) Results: LD (≤ 0.1 Gy) of ionizing radiation promoted the proliferation and survival of ADSCs. Within this dose range neither geno- nor cytotoxic effects were detectable. In contrast, greater doses within the dose range of >0.1-2.0 Gy induced residual double-strand breaks and reduced the long-term survival, as well as the proliferation rate of ADSCs. (4) Conclusions: Our data suggest that ADSCs are resistant to LD-IR. Furthermore, LD-IR could be a possible mediator to improve approaches of stem cells in the field of regenerative medicine.

The main objective of this work is to quantify the impact of photodynamic/photothermal treatment by using visible LED and NIR laser irradiation through the skin of subcutaneous fat in vivo followed up by tissue sampling and histology. The optical method may provide reduction of regional or site-specific accumulations of abdominal or subcutaneous adipose tissue precisely and least-invasively by inducing cell apoptosis and controlled necrosis of fat tissue. As photodynamic/photothermal adipose tissue sensitizers Brilliant Green (BG) or Indocyanine Green (ICG) dyes were injected subcutaneously in rats. The CW LED device (625 nm) or CW diode laser (808 nm) were used as light sources, respectively. Biopsies of skin together with subcutaneous tissues were taken for histology. The combined action BG-staining and LED-irradiation (BG + LED) or ICG-staining and NIR-laser irradiation (ICG + NIR) causes pronounced signs of damage of adipose tissue characterized by a strong stretching, thinning, folding and undulating of cell membranes and appearance of necrotic areas. As a posttreatment after 14 days only connective tissue was observed at the site of necrotic areas. The data obtained are important for safe light treatment of site-specific fat accumulations, including cellulite. This work provides a basis for the development of fat lipolysis technologies and to move them to clinical applications. Schematics of animal experiment., (© 2019 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.)

Multiple sclerosis (MS) is a progressive demyelinating disease of the central nervous system that destroys oligodendrocytes. This work aims to evaluate the treatment of experimentally induced MS in dogs using laser activated non-expanded adipose derived stem cells. The results showed amelioration of the clinical signs over time confirmed by the resolution of the previous lesions on MRI. Positive migration of the injected cells to the site of lesion, increased remyelination detected by Myelin Basic Proteins, positive differentiation into Olig2 positive oligodendrocytes, prevented the glial scar formation and restored axonal architecture. The study concluded that treatment using laser activated stem cells holds a promising therapeutic option for treatment of MS in a canine model., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Introduction: During radiation treatment planning, the small bowel (SB) is often contoured as a 'bowel bag' encompassing the entire peritoneal space that may be occupied by SB. This method incorporates large volumes of visceral adipose, potentially resulting in misleading estimates of radiation dose to the SB. We evaluated the relative volume of adipose within the peritoneal space and applied this as a correction factor to standard bowel bag dosimetric measures, hypothesizing that corrected SB measures would better correlate with acute toxicity., Methods: Eighteen consecutive patients receiving pelvic radiation for gynaecologic cancers over a 1-year period at an academic medical centre were included. Bowel function was assessed with the Expanded Prostate Index Composite (EPIC) questionnaire. Bowel bags were contoured on simulation computed tomography (CT) scans. Adipose was auto-contoured using previously published Hounsfield Unit criteria and used to create an adipose correction factor (ACF). The ACF was applied to V45 cc and V40% volumes to create adipose corrected measures (AC-V45 cc and AC-V40%). Correlations between EPIC scores and dosimetric measures were assessed using Spearman coefficients., Results: V45 cc and V40% did not correlate with overall EPIC bowel domain score; however, AC-V40% did show a significant correlation (P = 0.02). Correlations of V45 cc and V40% with the bowel bother subdomain of EPIC were both significantly improved by applying the ACF (P = 0.02 for AC-V45 cc; P < 0.01 for AC-V40%)., Conclusions: Adipose corrected bowel bag dosimetric constraints correlate better with acute bowel toxicity than current standard practice. Longer follow-up is needed to determine if similar findings are seen with late toxicity., (© 2019 The Royal Australian and New Zealand College of Radiologists.)

The aim of the present study was to synthesize mixture solutions which can accurately mimic the dielectric properties of biological tissues, specifically muscle and adipose tissues between 500 MHz and 50 GHz. Mixtures utilizing concentrations of bovine serum albumin (BSA) dissolved in phosphate buffered saline (PBS) and Ringer's solutions were synthesized to mimic in vivo and ex vivo muscle tissues. Solutions consisting of concentrations of peanut oil and Triton X-100 (TX) in PBS and Ringer's solutions were also synthesized to mimic in vivo and ex vivo adipose tissue. Results were then analysed and compared to measured dielectric properties of in vivo and ex vivo biological tissues from another previous study. Good agreement with said dielectric property measurements were obtained since the solutions from this study yielded low RMSE and RMSRE values. This implied that such solutions can be utilized in the construction of human body phantoms for narrowband and ultra-wideband microwave devices for near field breast cancer imaging.

Ultrasound tissue characterization based on the coefficient of nonlinearity, β n  = 1 + B/2A, has been demonstrated to produce added diagnostic value due to its large variation and sensitivity to tissue structure. However, the parameter has been observed to be significantly correlated to the speed of sound and density. These relationships are analyzed empirically as well as theoretically by developing a pressure-density relation based on a thermodynamic model and the Mie intermolecular potential. The results indicate that for many soft tissues, the coefficient of nonlinearity is largely determined by the isentropic compressibility, κ s . Consequently, for tissue characterization, estimating the nonlinear response of the medium, given by β p  = β n κ s , appears to be beneficial due to correlated quantities.

Background and Objectives: Conventional treatment options for eyelid fat bulging are generally limited to surgical approaches. However, many attempts have been made recently to manage this disfigurement using non-surgical interventions. The purpose of this study was to evaluate the efficacy and safety of a micro-insulated needle radiofrequency system for the treatment of lower eyelid fat bulging., Methods: This is a single center pre-post comparative study. Twenty-two subjects with lower eyelid fat bulging were treated twice using the needle radiofrequency system, at an interval of four weeks. Two types of partially insulated needles with different lengths were used in each session. A three-dimensional photogrammetry system was used to objectively measure changes in the extent of the fat bulge. The investigator's global assessment (IGA) of the severity of fat bulging was also evaluated., Results: The average extent of fat bulging was decreased significantly after twelve weeks, and was maintained until 24 weeks. The IGA score was significantly decreased after four weeks and further decreased after twelve weeks, and then maintained until 24 weeks. There were no side effects, except for lower eyelid swelling and bruising that lasted for about a week., Conclusion: The micro-insulated needle radiofrequency system can be a beneficial and well-tolerated treatment for lower eyelid fat bulging., (© 2019 Deutsche Dermatologische Gesellschaft (DDG). Published by John Wiley & Sons Ltd.)

The application of light in various therapeutic settings known as Photobiomodulation (PBM) is well established. Indications are the improvement of wound healing and tissue regeneration, scarring, and perfusion as well as pain therapy. Tissue perfusion is mandatory for successful wound healing. Nevertheless, there is a lack of mechanistic studies. We investigate the potential effect of PBM from light emitting diodes (LED) at 635 nm, 80 mW/cm 2 , 24 J/cm 2 on angiogenesis in a two-part study: 1.) Investigation of the effect of PBM on the proliferation of endothelial cells and on vasculogenesis in a co-culture model of endothelial cells and stem cells. 2.) Investigation of the influence of PBM at chick egg chorioallantoic membrane (CAM) assays with fresh human skin xenografts. In both study phases, we observed a stimulating effect of PBM at 635 nm; in part 1: for proliferation of HUVEC (human umbilical vein endothelial cells) (25833 ± 12859 versus 63002 ± 35760 cells/well, p < 0.05, for cellular network formation (2.1 ± 2.1 versus 4.6 ± 3.5, p < 0.05) and for less cell compactness p = 0.01; in part 2: for the increase of number of vessel junctions per ROI (region of interest) (15.9 ± 2.6 versus 20.8 ± 5.4, p < 0.05). Our results suggest significant promotion of angiogenesis by PBM at 635 nm in vitro and in vivo.

Background: Equipment that acts in the reduction in adipose tissue are becoming widely investigated. One of the resources that begin to gain recognition is radiofrequency., Purpose: To verify the existence of scientific evidence and the methodological quality of the articles on the effects of radiofrequency in the reduction in adipose tissue., Methodology: Systematic review with meta-analysis on the effects of radiofrequency on adipose tissue. The research was carried out using several databases and including experimental studies only in humans. The evaluation of the methodological quality of the articles was done based on the PEDro Scale., Results: Twelve articles related with adipose tissue and cellulitis were included. There was a great variability of protocols, and the methodological quality was generally low and the methods most used for the evaluation of results were anthropometry, photography, and histopathology. Clinical results suggest a positive effect of radiofrequency on the reduction in adipose tissue, proving an increase in adipocyte lipolysis. After statistical analysis, it was verified that the anthropometry presented questionable results., Conclusion: The clinical results of the studies point to the positive effects of radiofrequency on the reduction in adipose tissue; however, the low methodological make this topic still debatable, requiring more controlled studies., (© 2018 Wiley Periodicals, Inc.)

Beige adipocytes are an inducible form of thermogenic adipocytes that become interspersed within white adipose tissue (WAT) depots in response to cold exposure. Previous studies have shown that type 2 cytokines and M2 macrophages induce cold-induced browning in inguinal WAT (ingWAT) by producing catecholamines. Exactly how the conditional and partial depletion of CD206 + M2-like macrophages regulates the cold-induced browning of ingWAT, however, remains unknown. We examined the role of CD206 + M2-like macrophages in the cold-induced browning of WAT using genetically engineered CD206DTR mice, in which CD206 + M2-like macrophages were conditionally depleted. The partial depletion of CD206 + M2-like enhanced UCP1 expression in ingWAT, as shown by immunostaining, and also upregulated the expression of Ucp1 and other browning-related marker genes in ingWAT after cold exposure. A flow cytometry analysis showed that the partial depletion of CD206 + M2-like macrophages caused an increase in the number of beige progenitors in ingWAT in response to cold. Thus, we concluded that CD206 + M2-like macrophages inhibit the proliferation of beige progenitors and that the partial depletion of CD206 + M2-like macrophages releases this inhibition, thereby enhancing browning and insulin sensitivity.

High-intensity focused ultrasound (HIFU) under magnetic resonance imaging (MRI) guidance can achieve a noninvasive and precise ablation of the solid tumor. In the study, an MRI-compatible 1-MHz 16-channel ring-shaped transducer was developed to minimize the burn risk of breast skin and perform volumetric ablation for short treatment time. The measured electroacoustic conversion efficiency of the transducer was 50.90% ± 5. The transducer could produce a point and a quasi-hollow-cylinder lesion in a thermal-sensitive phantom or an ex vivo pork by tuning the phase of each element. It may achieve volumetric ablation of 1.5 cm 3 when the point lesion is located inside the hollow lesion. Ex vivo ablation experiments showed that the transducer could cause a coagulative necrosis in the pork from the surrounded subcutaneous fat by 5 mm without fat damage. The temperature and region of the pork ablation were quantified by MRI technique. There was no MRI interference from HIFU and vice versa while both systems operated concurrently.

Dosimetry of proton beams is generally evaluated in liquid water, or alternatively in solid phantoms via water equivalent ratios (WER). WER is defined as the ratio of proton range in liquid water to that in a phantom of certain material. Presently, WER is not available in the literature neither for a wide range of energies nor for variety of relevant materials. Thus, the goal of this study is to provide such data through Monte Carlo simulations. WER is calculated for 10-500 MeV energies for compact bone, adipose tissue, polymethyl methacrylate (PMMA), PTFE (teflon), graphite (C), aluminum (Al), copper (Cu), titanium (Ti), and gold (Au) using MCNPX.2.70, GEANT4, and FLUKA Monte Carlo (MC) codes. The MCNPX code was considered as the reference to which other codes were compared. The mean values of WER obtained through the MCNPX simulations for Au, Cu, Ti, Al, PTFE, graphite, PMMA, bone, and adipose tissue were 8.83, 5.40, 3.18, 2.03, 1.87, 1.52, 1.13, 1.71, and 0.96, respectively, for 10-500 MeV energy range. The maximum deviations of WER values between MCNPX and GEANT4 results were about 6.85% for adipose tissue at energies  <20 MeV, whereas they were about 7.74%, 7.74% between MCNPX and FLUKA, for adipose and Al, respectively. This inter-code uncertainties are mainly due to different physic models and stopping powers in each code. Comparing the results to that in the literature, the range of discrepancy was found to be 0-8% with greatest discrepancy for Au. Based on the materials evaluated, the PMMA remained the closest to water, for a non-tissue solid material, with an average WER of 1.13, for proton energy ranging 10-500 MeV.

Within their niche, adipose-derived stem cells (ADSCs) are essential for homeostasis as well as for regeneration. Therefore, the interest of physicians is to use ADSCs as a tool for radiation oncology and regenerative medicine. To investigate related risks, this study analyses the radiation response of adult stem cells isolated from the adipose tissue of the female breast. To avoid donor-specific effects, ADSCs isolated from breast reduction mammoplasties of 10 donors were pooled and used for the radiobiological analysis. The clonogenic survival fraction assay was used to classify the radiation sensitivity in comparison to a more radiation-sensitive (ZR-75-1), moderately sensitive (MCF-7), and resistant (MCF10A) cell lines. Afterwards, cytotoxicity and genotoxicity of irradiation on ADSCs were investigated. On the basis of clonogenic cell survival rates of ADSCs after irradiation, we assign ADSCs an intermediate radiation sensitivity. Furthermore, a high repair capacity of double-strand breaks is related to an altered cell cycle arrest and increased expression of cyclin-dependent kinase (CDK) inhibitor p21. ADSCs isolated from breast tissue exhibit intermediate radiation sensitivity, caused by functional repair mechanisms. Therefore, we propose ADSCs to be a promising tool in radiation oncology.

As aging involves oxidant injury, we examined the role of the recently described Na/K-ATPase oxidant amplification loop (NKAL). First, C57Bl6 old mice were given a western diet to stimulate oxidant injury or pNaKtide to antagonize the NKAL. The western diet accelerated functional and morphological evidence for aging whereas pNaKtide attenuated these changes. Next, human dermal fibroblasts (HDFs) were exposed to different types of oxidant stress in vitro each of which increased expression of senescence markers, cell-injury, and apoptosis as well as stimulated the NKAL. Further stimulation of the NKAL with ouabain augmented cellular senescence whereas treatment with pNaKtide attenuated it. Although N-Acetyl Cysteine and Vitamin E also ameliorated overall oxidant stress to a similar degree as pNaKtide, the pNaKtide produced protection against senescence that was substantially greater than that seen with either antioxidant. In particular, pNaKtide appeared to specifically ameliorate nuclear oxidant stress to a greater degree. These data demonstrate that the NKAL is intimately involved in the aging process and may serve as a target for anti-aging interventions.

Background: Monte Carlo simulations were run to estimate the dose variations generated by thedifference arising from the chemical composition of the tissues., Methods: CT datasets of five breast cancer patients were selected. Mammary gland was delineated as clinical target volume CTV, as well as CTV&#95;lob and CTV&#95;fat, being the lobular and fat fractions of the entire mammary gland. Patients were planned for volumetric modulated arc therapy technique, optimized in the Varian Eclipse treatment planning system. CT, structures and plans were imported in PRIMO, based on Monte Carlo code Penelope, to run three simulations: AdiMus, where the adipose and muscle tissues were automatically assigned to fat and lobular fractions of the breast; Adi and Mus, where adipose and muscle, respectively were assigned to the whole mammary gland. The specific tissue density was kept identical from the CT dataset. Differences in mean doses in the CTV&#95;lob and CTV&#95;fat structures were evaluated for the different tissue assignments. Differences generated by the tissue composition and estimated by Acuros dose calculations in Eclipse were also analysed., Results: From Monte Carlo simulations, the dose in the lobular fraction of the breast, when adipose tissue is assigned in place of muscle, is overestimated by 1.25 ± 0.45%; the dose in the fat fraction of the breast with muscle tissue assignment is underestimated by 1.14 ± 0.51%. Acuros showed an overestimation of 0.98 ± 0.06% and an underestimation of 0.21 ± 0.14% in the lobular and fat portions, respectively. Reason of this dissimilarity resides in the fact that the two calculations, Monte Carlo and Acuros, differently manage the range of CT numbers and the material assignments, having Acuros an overlapping range, where two tissues are both present in defined proportions., Conclusion: Although not clinically significant, the dose deposition difference in the lobular and connective fat fraction of the breast tissue lead to an improved knowledge of the possible dose distribution and homogeneity in the breast radiation treatment.

Radiofrequency-assisted liposuction is a relatively new concept in energy-assisted body contouring techniques and has received instrument approval. This supplemental article reviews the clinical application of electromagnetic energy via the BodyTite (InMode Corporation, Toronto, Canada) device on soft tissues during suction lipectomy, its effect on soft tissue contraction, and its use in aesthetic body contouring in various clinical scenarios.

Obesity represents a continuously growing global epidemic and is associated with the development of type 2 diabetes mellitus. The etiology of type 2 diabetes is related to the resistance of insulin-sensitive tissues to its action leading to impaired blood glucose regulation. Photobiomodulation (PBM) therapy might be a non-pharmacological, non-invasive strategy to improve insulin resistance. It has been reported that PBM therapy in combination with physical exercise reduces insulin resistance. Therefore, the aim of this study was to investigate the effects of PBM therapy on insulin resistance in obese mice. Male Swiss albino mice received low-fat control diet (n = 16, LFC) or high-fat diet (n = 18, HFD) for 12 weeks. From 9th to 12th week, the mice received PBM therapy (LASER) or Sham (light off) treatment and were allocated into four groups: LFC Sham (n = 8), LFC PBM (n = 8), HFD Sham (n = 9), and HFD PBM (n = 9). The PBM therapy was applied in five locations: to the left and right quadriceps muscle, upper limbs and center of the abdomen, during 40 s at each point, once a day, 5 days a week, for 4 weeks (780 nm, 250 mW/cm 2 , 10 J/cm 2 , 0.4 J per site; 2 J total dose per day). Insulin signaling pathway was evaluated in the epididymal adipose tissue. PBM therapy improved glucose tolerance and phosphorylation of Akt (Ser473) and reversed the HFD-induced reduction of GLUT4 content and phosphorylation of AS160 (Ser588). Also, PBM therapy reversed the increased area of epididymal and mesenteric adipocytes. The results showed that chronic PBM therapy improved parameters related to obesity and insulin resistance in HFD-induced obesity in mice.

Background and Objectives: The aim of this study was to develop experimental and numerical models for a better understanding of hyperthermic laser lipolysis (HHL)., Study Design: A 3 cm thick porcine fat sample was irradiated over a 4.3 × 4.7 cm 2 area for 2 minutes with a 1,064 nm Nd:YAG laser using 1.2 W/cm 2 irradiance. Two irradiation scenarios were considered: without and with forced air cooling. Following the irradiation, the sample was left to cool down by natural convection. During the irradiation period, the surface temperature of the sample was continuously recorded by an infrared camera. Additionally, temperature depth profiles during the cooling period were also obtained. A one-dimensional model of the laser irradiation procedure was developed, including light and heat transport. The model was used to determine the absorption coefficient of the fat and the heat convection coefficients from the measured data, and to evaluate the treatment by varying the parameters., Results: The measured temperature depth profiles revealed a maximum temperature (45.5°C) at the surface for a non-cooled sample, and a surface temperature of 38°C with a subsurface temperature peak of 42.6°C at a depth of 5.7 mm for a cooled sample. This corresponded well with the measured surface temperature increase following the irradiation as a result of heat diffusion from the heated deeper fat layers. The developed numerical model was used to fit the measured data. A good agreement between the model and the measurements was obtained. By varying the treatment parameters, basic empirical relations connecting the treatment, thermal signal, and temperature depth profile parameters were found., Conclusions: The results of this study provide a better understanding of transcutaneous laser lipolysis. The developed numerical model can be extended to transcutaneous laser lipolysis of human subjects. Lasers Surg. Med. 50:125-136, 2018. © 2017 Wiley Periodicals, Inc., (© 2017 Wiley Periodicals, Inc.)

In this study, we investigated microvascular perfusion status, changes to fat content and fatty acid composition in the bone marrow of rat femurs after total-body irradiation by quantitative permeability parameters of dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) and ex vivo high-resolution magic angle spinning (HRMAS) 1 H nuclear magnetic resonance spectroscopy (NMRS). Thirty-six Sprague-Dawley rats were randomly assigned to either an irradiated or nonirradiated control group. Permeability imaging using DCE-MRI and HRMAS 1 H NMRS was performed before irradiation, as well as at days 4 and 7 postirradiation. The volume transfer constant (K trans ) values increased to 2.219 ± 0.418/min ( P < 0.01) at day 4 and to 2.760 ± 0.217/min at day 7 ( P < 0.01) postirradiation. The plasma fraction (v p ) values gradually decreased. The proportion of (n-6) polyunsaturated fatty acids (PUFA) gradually reached a peak at day 7, the proportion of (n-3) PUFA gradually decreased and the proportion of saturated fatty acids gradually increased. After irradiation, K trans at different times showed significant negative correlation with (n-3) PUFA ( r = -0.6393, P < 0.01) and significant positive correlation with (n-6) PUFA ( r = 0.6841, P < 0.05). These findings indicate that bone marrow microcirculation perfusion and vascular permeability correlated with fat content at an early time point after irradiation. A pathophysiological mechanism may exist based on fat-vascular permeability in the case of injury to bone marrow microcirculation.

Background: Despite significant achievements in the field of tissue engineering, simplification and improvement of the existing protocols are of great importance. The use of complex differentiation media, due to the presence of multiple factors, may have some undesired effects on cell health and functions. Thus, minimizing the number of involved factors, while maintaining the differentiation efficiency, provides less costly and controllable conditions. Adipose-derived Mesenchymal stem cells (ASCs), the adult stem cells present in adipose tissue, can be a suitable source of stem cells due to abundant and ease of access. The aim of this study is to optimize the osteogenic differentiation of ASCs by chemical composition of scaffold, in the first step, and then by electromagnetic treatments., Methods: ASCs were cultured on PVA/PES scaffold and tissue culture polystyrene surfaces (TCPS) and osteogenic differentiation was performed with either osteogenic medium, or electromagnetic field or both. The impact of each treatment on ASCs growth and proliferation was measured by MTT assay. Changes in gene expression levels of osteogenic-specific markers including ALP and RUNX2 were determined by Real Time PCR. Furthermore, alkaline phosphatase activity and calcium deposition were measured., Results: The MTT assay showed the significant effects on cell growth and respiration in scaffold-seeded ASCs treated with electromagnetic field, compared to control TCPS plate. Also, the electromagnetic treatment, increased alkaline phosphatase activity and calcium deposition. Finally, Real Time PCR showed higher expression of ALP and RUNX2 genes in electromagnetic field groups compared to control groups., Conclusion: It can be concluded that PVA/PES scaffold used in this study improved the osteogenic capacity of ASCs. Moreover, the osteogenic potential of ASCs seeded on PVA/PES scaffold could be augmented by electromagnetic field without any chemical stimulation., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Objective: The aim of this study was to verify if the exposure to the pulsed electromagnetic eld (PEMF) influenced the release of proinflammatory cytokines from adipose-derived stem cells (ADSCs) of normal and overweight rats of various age and sex. Moreover, we compared body temperatures of normal-weight and overweight rats., Methods: ADSCs of Wistar rats were isolated from the subcutaneous area in females and paratesticular region in males, cultured and exposed to PEMF (7 Hz, 30 mT). Concentrations of proinflammatory cytokines were determined in rat sera and supernatant from ADSCs cultures exposed and non-exposed to PEMF. Body temperature (BT) was measured twice a week, using an infrared and rectal thermometer., Results: Irrespective of age and sex, animals maintained on low-fat (LF) diet had higher BT than those grown on high-fat (HF) diet. Exposure to PEMF reduced the release of TNF-α and enhanced the production of IL-6 in ADSCs cultures from female pups maintained on LF diet. In contrast, a decrease in IL-6 level was observed in PEMF-exposed ADSCs cultures from female pups grown on HF diet. A similar phenomenon, i.e. a post-exposure increase in IL-6 level was also observed in male pups fed with the LF diet. In the case of ADSCs cultures from adult rats maintained on an HF diet, either males or females, PEMF exposure contributed to a dramatic increase in TNF-α production., Conclusion: Our findings suggest that PEMF exposure may affect the production of proinflammatory cytokines in ADSCs cultures. The intergroup differences in BT may result from the presence of an underlying inflammation in obese rats.