Exogenous APN protects normal tissues from radiation-induced oxidative damage and fibrosis in mice and prostate cancer patients with higher levels of APN have less radiation-induced toxicities.

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.

Impact on the estimated dose of different tissue assignment strategies during partial breast irradiations with INTRABEAM.

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.

Exploring the biphasic dose-response effects of photobiomodulation on the viability, migration, and extracellular vesicle secretion of human adipose mesenchymal stem cells.

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/cm2), with the 5 J/cm2 group showing significantly higher cell viability and migration ability than other groups. Additionally, at the optimal dose of 5 J/cm2, 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.

Effects of 3.5-GHz radiofrequency radiation on energy-regulatory hormone levels in the blood and adipose tissue.

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.

NIR irradiation of human buccal fat pad adipose stem cells and its effect on TRP ion channels.

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/cm2 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).

Effects of LED photobiomodulation therapy on the subcutaneous fatty tissue of obese individuals - histological and immunohistochemical analysis.

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.

Assessment of Mechanical Stress Induced by Radiofrequency Currents on Skin Interfaces.

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.

Tightening and Reduction of Unwanted Submental Fat Using Triple-Layer High-Intensity Focused Ultrasound: Clinical and 3-Dimensional Imaging Analysis.

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.

Therapeutic radiation exposure of the abdomen during childhood induces chronic adipose tissue dysfunction.

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).

Finite element modeling of Non-Fourier heat transfer in a cancerous tissue with an injected fat layer during hyperthermia treatment.

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.

NIR Irradiation Based on Low-Power LED Drive Module Design for Fat Reduction.

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.

Changes in ionizing radiation dose rate affect cell cycle progression in adipose derived stem cells.

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.

Targeted peripheral focused ultrasound stimulation attenuates obesity-induced metabolic and inflammatory dysfunctions.

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.

Chronic circadian shift leads to adipose tissue inflammation and fibrosis.

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.

APPLICATION OF QUERCETIN FOR CORRECTION OF THE IMPAIRMENT OF THE FUNCTIONAL STATE OF THE ENDOTHELIUS OF VESSELS (CLINICAL AND EXPERIMENTAL STUDY). / ZASTOSUVANNIa KVERTsETYNU DLIa KOREKTsIÏ PORUShEN' FUNKTsIONAL'NOGO STANU ENDOTELIIu SUDYN (KLINIKO-EKSPERYMENTAL'NE DOSLIDZhENNIa).

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.

Impact of low-intensity pulsed ultrasound on transcription and metabolite compositions in proliferation and functionalization of human adipose-derived mesenchymal stromal cells.

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/cm2 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 G1 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/cm2 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.

Evaluation of Stromal Vascular Fraction Properties and Histological Changes of Regenerating Tissue during Healing of Radiation-Induced Lesions in the Rectum.

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.

Analysis of low-level laser transmission at wavelengths 660, 830 and 904 nm in biological tissue samples.

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.

A Combinational Therapy of Articular Cartilage Defects: Rapid and Effective Regeneration by Using Low-Intensity Focused Ultrasound After Adipose Tissue-Derived Stem Cell Transplantation.

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.

Wireless optogenetics protects against obesity via stimulation of non-canonical fat thermogenesis.

Cold stimuli and the subsequent activation of ß-adrenergic receptor (ß-AR) potently stimulate adipose tissue thermogenesis and increase whole-body energy expenditure. However, systemic activation of the ß3-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 ß-AR pathway and triggers Ca2+ cycling selectively in adipocytes. The wireless optogenetics stimulation in the subcutaneous adipose tissue potently activates Ca2+ 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.