Recent Advances in Basic Studies of Low-Intensity Pulsed Ultrasound in Periodontal Tissue Regeneration: A Systematic Review.

Approximately half of the adult population is suffering from periodontal disease, and conventional periodontal treatment strategies can only slow the progression of the disease. As a kind of tissue engineering, periodontal regeneration brings hope for the treatment of periodontal disease. Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound with a frequency of 1-3 MHz and a much lower intensity (< 1W/cm2) than traditional ultrasound energy and output. LIPUS has been adopted for a variety of therapeutic purposes due to its bioeffects such as thermal, mechanical, and cavitation effects, which induce intracellular biochemical effects and lead to tissue repair and regeneration ultimately. In this systematic review, we summarize the basic research of LIPUS in the treatment of periodontal disease in periodontal disease animal models and the influence of LIPUS on the biological behavior (including promoting osteogenic differentiation of stem cells and inhibiting inflammatory response) and potential mechanism of periodontal ligament stem cells (PDLSCs), hoping to provide new ideas for the treatment of periodontal disease. We believe that LIPUS can be used as an auxiliary strategy in the treatment of periodontal disease and play an exciting and positive role in periodontal regeneration.

Tumor perfusion enhancement by microbubbles ultrasonic cavitation reduces tumor glycolysis metabolism and alleviate tumor acidosis.

The tumor microenvironment is increasingly acknowledged as a critical contributor to cancer progression, mediating genetic and epigenetic alterations. Beyond diverse cellular interactions from the microenvironment, physicochemical factors such as tumor acidosis also significantly affect cancer dynamics. Recent research has highlighted that tumor acidosis facilitates invasion, immune escape, metastasis, and resistance to therapies. Thus, noninvasive measurement of tumor acidity and the development of targeted interventions represent promising strategies in oncology. Techniques like contrast-enhanced ultrasound (CEUS) can effectively assess blood perfusion, while ultrasound-stimulated microbubble cavitation (USMC) has proven to enhance tumor blood perfusion. We therefore aimed to determine whether CEUS assesses tumor acidity and whether USMC treatment can modulate tumor acidity. Firstly, we tracked CEUS perfusion parameters in MCF7 tumor models and compared them with in vivo tumor pH recorded by pH microsensors. We found that the peak intensity and area under curve of tumor contrast-enhanced ultrasound correlated well with tumor pH. We further conducted USMC treatment on MCF7 tumor-bearing mice, tracked changes of tumor blood perfusion and tumor pH in different perfusion regions before and after the USMC treatment to assess its impact on tumor acidity and optimize therapeutic ultrasound pressure. We discovered that USMC with 1.0 Mpa significantly improved tumor blood perfusion and tumor pH. Furthermore, tumor vascular pathology and PGI2 assays indicated that improved tumor perfusion was mainly due to vasodilation rather than angiogenesis. More importantly, analysis of glycolysis-related metabolites and enzymes demonstrated USMC treatment can reduce tumor acidity by reducing tumor glycolysis. These findings support that CEUS may serve as a potential biomarker to assess tumor acidity and USMC is a promising therapeutic modality for reducing tumor acidosis.

Effect of low-intensity pulsed ultrasound on the mineralization of force-treated cementoblasts and orthodontically induced inflammatory root resorption via the Lamin A/C-Yes associated protein axis.

AIMS: Orthodontic treatment commonly results in orthodontically induced inflammatory root resorption (OIIRR). This condition arises from excessive orthodontic force, which triggerslocal inflammatory responses and impedes cementoblasts' mineralization capacity. Low-intensity pulsed ultrasound (LIPUS) shows potential in reducing OIIRR. However, the precise mechanisms through which LIPUS reduces OIIRR remain unclear. This study aimed to explore the effects and mechanisms of LIPUS on the mineralization of force-treated cementoblasts and its impact on OIIRR. METHODS: We established a rat OIIRR model and locally administered LIPUS stimulation for 7 and 14 days. We analyzed root resorption volume, osteoclast differentiation, and the expression of osteocalcin and yes-associated protein 1 (YAP1) using micro-computed tomography (micro-CT), hematoxylin and eosin, tartrate-resistant acid phosphatase, immunofluorescence and immunohistochemistry staining. In vitro, we applied compressive force and LIPUS to the immortalized mouse cementoblasts (OCCM30). We assessed mineralization using alkaline phosphatase (ALP) staining, alizarin red staining, real-time quantitative polymerase chain reaction, Western blotting and immunofluorescence staining. RESULTS: In rats, LIPUS reduced OIIRR, as evidenced by micro-CT analysis and histological staining. In vitro, LIPUS enhanced mineralization of force-treated OCCM30 cells, as indicated by ALP and alizarin red staining, upregulated mRNA expression of mineralization-related genes, and increased protein expression of mineralization markers. Mechanistically, LIPUS activated YAP1 signaling via the cytoskeleton-Lamin A/C pathway, supported by immunofluorescence and Western blot analysis. CONCLUSION: This study demonstrates that LIPUS promotes mineralization in force-treated cementoblasts and reduces OIIRR by activating YAP1 through the cytoskeletal-Lamin A/C signaling pathway. These findings provide fresh insights into how LIPUS benefits orthodontic treatment and suggest potential strategies for preventing and treating OIIRR.

Low-intensity pulsed ultrasound improves myocardial ischaemia‒reperfusion injury via migrasome-mediated mitocytosis.

During myocardial ischaemia‒reperfusion injury (MIRI), the accumulation of damaged mitochondria could pose serious threats to the heart. The migrasomes, newly discovered mitocytosis-mediating organelles, selectively remove damaged mitochondria to provide mitochondrial quality control. Here, we utilised low-intensity pulsed ultrasound (LIPUS) on MIRI mice model and demonstrated that LIPUS reduced the infarcted area and improved cardiac dysfunction. Additionally, we found that LIPUS alleviated MIRI-induced mitochondrial dysfunction. We provided new evidence that LIPUS mechanical stimulation facilitated damaged mitochondrial excretion via migrasome-dependent mitocytosis. Inhibition the formation of migrasomes abolished the protective effect of LIPUS on MIRI. Mechanistically, LIPUS induced the formation of migrasomes by evoking the RhoA/Myosin II/F-actin pathway. Meanwhile, F-actin activated YAP nuclear translocation to transcriptionally activate the mitochondrial motor protein KIF5B and Drp1, which are indispensable for LIPUS-induced mitocytosis. These results revealed that LIPUS activates mitocytosis, a migrasome-dependent mitochondrial quality control mechanism, to protect against MIRI, underlining LIPUS as a safe and potentially non-invasive treatment for MIRI.

Effects of low-intensity pulsed ultrasound on the microorganisms of expressed prostatic secretion in patients with IIIB prostatitis.

To detect and analyze the changes of microorganisms in expressed prostatic secretion (EPS) of patients with IIIB prostatitis before and after low-intensity pulsed ultrasound (LIPUS) treatment, and to explore the mechanism of LIPUS in the treatment of chronic prostatitis (CP). 25 patients (study power was estimated using a Dirichlet-multinomial approach and reached 96.5% at α = 0.05 using a sample size of 25) with IIIB prostatitis who were effective in LIPUS treatment were divided into two groups before and after LIPUS treatment. High throughput second-generation sequencing technique was used to detect and analyze the relative abundance of bacterial 16 s ribosomal variable regions in EPS before and after treatment. The data were analyzed by bioinformatics software and database, and differences with P < 0.05 were considered statistically significant. Beta diversity analysis showed that there was a significant difference between groups (P = 0.046). LEfSe detected four kinds of characteristic microorganisms in the EPS of patients with IIIB prostatitis before and after LIPUS treatment. After multiple comparisons among groups by DESeq2 method, six different microorganisms were found. LIPUS may improve patients' clinical symptoms by changing the flora structure of EPS, stabilizing and affecting resident bacteria or opportunistic pathogens.

[Micro-energy medicine in the treatment of erectile dysfunction: An update].

Erectile dysfunction (ED) is one of the most common sexual disorders in males, which seriously affects the health of the patient and well-being of the family. The therapeutic strategy of ED is an individualized comprehensive treatment based on phosphodiesterase inhibitors. At present, as a new option for the treatment of ED, micro-energy medicine has attracted more and more attention in its therapeutic effects and advantages. This article presents an overview of the progress in the studies of micro-energy medicine in the treatment of ED.

Stimuli-Responsive Codelivery System-Embedded Polymeric Nanofibers with Synergistic Effects of Growth Factors and Low-Intensity Pulsed Ultrasound to Enhance Osteogenesis Properties.

The present work aims to develop optimized scaffolds for bone repair by incorporating mesoporous nanoparticles into them, thereby combining bioactive factors for cell growth and preventing rapid release or loss of effectiveness. We synthesized biocompatible and biodegradable scaffolds designed for the controlled codelivery of curcumin (CUR) and recombinant human bone morphogenic protein-2 (rhBMP-2). Active agents in dendritic silica/titania mesoporous nanoparticles (DSTNs) were incorporated at different weight percentages (0, 2, 5, 7, 9, and 10 wt %) into a matrix of polycaprolactone (PCL) and polyethylene glycol (PEG) nanofibers, forming the CUR-BMP-2@DSTNs/PCL-PEG delivery system (S0, S2, S5, S7, S9, and S10, respectively, with the number showing the weight percentage). To enhance the formation process, the system was treated using low-intensity pulsed ultrasound (LIPUS). Different advanced methods were employed to assess the physical, chemical, and mechanical characteristics of the fabricated scaffolds, all confirming that incorporating the nanoparticles improves their mechanical and structural properties. Their hydrophilicity increased by approximately 25%, leading to ca. 53% enhancement in their water absorption capacity. Furthermore, we observed a sustained release of approximately 97% for CUR and 70% for BMP-2 for the S7 (scaffold with 7 wt % DSTNs) over 28 days, which was further enhanced using ultrasound. In vitro studies demonstrated accelerated scaffold biodegradation, with the highest level observed in S7 scaffolds, approximately three times higher than the control group. Moreover, the cell viability and proliferation on DSTNs-containing scaffolds increased when compared to the control group. Overall, our study presents a promising nanocomposite scaffold design with notable improvements in structural, mechanical, and biological properties compared to the control group, along with controlled and sustained drug release capabilities. This makes the scaffold a compelling candidate for advanced bone tissue engineering and regenerative therapies.

Reversible opening of the blood-labyrinth barrier by low-pressure pulsed ultrasound and microbubbles for the treatment of inner ear diseases.

Systemic drug administration provides convenience and non-invasive benefits for preventing and treating inner ear diseases. However, the blood-labyrinth barrier (BLB) restricts the transport of drugs to inner ear tissues. Ultrasound can stimulate specific areas and penetrate tissues, with the potential to overcome physiological barriers. We present a novel strategy based on low-pressure pulsed ultrasound assisted by microbubbles (USMB) to transiently open the BLB and deliver therapeutics into the inner ear. A pulsed ultrasound device with adjustable pressure was established; the generated ultrasound was transmitted through the external auditory canal into the guinea pig's inner ear. We observed that the application of microbubbles allowed the use of safe and efficient ultrasound conditions to penetrate the BLB. We found that USMB-mediated BLB opening seemed to be associated with a reduced expression of the tight junction proteins zonula occludens-1 and occludin. Following intravenous administration, hydrophilic dexamethasone sodium phosphate (DSP), hydrophobic curcumin (CUR), as well as drug-loaded nanoparticles (Fe3O4@CUR NPs) could be efficiently delivered into the inner ear. We observed better drug accumulation in the perilymph of the inner ear, resulting in less drug (cisplatin)-induced ototoxicity. Furthermore, physiological, hematological, and histological studies showed that the modulation of the BLB by low-pressure USMB was a safe process without significant adverse effects. We conclude that USMB could become a promising strategy for the systematic delivery of therapeutics in the treatment of inner ear diseases.

Low-intensity pulsed ultrasound combined with ST36 modulate gastric smooth muscle contractile marker expression via RhoA/Rock and MALAT1/miR-449a/DLL1 signaling in diabetic rats.

BACKGROUND: Low-intensity pulsed ultrasound (LIPUS) combined with acupoint can promote gastric motility of diabetic rats. The switch of gastric smooth muscle cell (GSMCs) phenotype was related to the diabetes-induced gastric dysfunction, but the mechanism is not clearly elucidated. This study was aimed at exploring the underlying mechanism of LIPUS stimulation application in diabetic gastroparesis rats. METHODS: In this study, Sprague-Dawley male rats were divided into three groups: control group (CON), diabetic gastroparesis group (DGP), and LIPUS-treated group (LIPUS). LIPUS irradiation was performed bilaterally at ST36 for 20 min per day for 4 weeks. The gastric emptying rate was measured by ultrasound examination. Contraction ability of GSMCs was assessed by muscle strip experiment. The expression of related proteins or mRNAs including α-SMA, SM22α, MHC, RhoA, Rock2, p-MYPT1, MYPT1, p-MLC, MLC, MALAT1, miR-449a, and DLL1 was detected by different methods such as western blotting, RT-qPCR, immunohistochemistry, and immunofluorescence staining, as appropriate. KEY RESULTS: (a) LIPUS stimulation at ST36 could improve the gastric motility dysfunction of diabetic rats. (b) LIPUS increased RhoA, Rock2, p-MYPT1, and p-MLC expression level. (c) MALAT1 and DLL1 contents were decreased, but the level of miR-449a was increased in the LIPUS group. CONCLUSIONS & INFERENCES: LIPUS may affect the contractile marker expression of gastric smooth muscle through the RhoA/Rock and MALAT1/miR-449a/DLL1 pathway to ameliorate DGP.

Ultrasound Therapy With High-Pressure Pulses Is Effective to Reduce the Effects of Collagenase-Induced Tendinopathy in Rat's Achilles Tendon.

OBJECTIVE: We propose an ultrasonic treatment for collagenase-induced tendinopathy in rat's Achilles tendon using pulses with a low number of cycles, high acoustic pressure and very low duty cycle. METHODS: Twenty rats were used to perform the experiment. Four experimental groups of calcaneal tendons were studied: control (n = 6), sham (n = 4), collagenase-induced tendinopathy (n = 8) and ultrasound-treated collagenase-induced tendinopathy (n = 8). Surgical intervention was performed to expose the tendons prior to collagenase injection. A 1 MHz ultrasonic tansducer with a focusing lens was used. Ultrasonic treatments were used with an average total treatment time of 2.5 min, 20-cycle pulses, pressure amplitude p = 7 MPa, and 0.02% duty cycle. Histopathology of the samples was performed to evaluate nuclear density, acute inflammation, and signs of neovascularization. Collagen (types I and III), elastic fibers, and glycosaminoglycans were also analyzed. RESULTS: No tendon involvement was found by the surgical process. Ultrasonic treatment is safe, as it does not affect healthy tendons. When collagenase infiltrated animals were treated with US, a clear predominance of type I collagen fibers and a similar collagen ratio profile to that observed in the control and sham groups was observed, with a higher density of elastic fibers compared to the control and sham groups and a significant increase in the density of glycosaminoglycans. CONCLUSION: The ultrasound treatment proposed reduces the effects of the artificial collagenase lesion to reach the basal level after 45 d.

Low-intensity pulsed ultrasound promotes the osteogenesis of mechanical force-treated periodontal ligament cells via Piezo1.

Background: Low-intensity pulsed ultrasound (LIPUS) can accelerate tooth movement and preserve tooth and bone integrity during orthodontic treatment. However, the mechanisms by which LIPUS affects tissue remodeling during orthodontic tooth movement (OTM) remain unclear. Periodontal ligament cells (PDLCs) are pivotal in maintaining periodontal tissue equilibrium when subjected to mechanical stimuli. One notable mechano-sensitive ion channel, Piezo1, can modulate cellular function in response to mechanical cues. This study aimed to elucidate the involvement of Piezo1 in the osteogenic response of force-treated PDLCs when stimulated by LIPUS. Method: After establishing rat OTM models, LIPUS was used to stimulate rats locally. OTM distance and alveolar bone density were assessed using micro-computed tomography, and histological analyses included hematoxylin and eosin staining, tartrate-resistant acid phosphatase staining and immunohistochemical staining. GsMTx4 and Yoda1 were respectively utilized for Piezo1 functional inhibition and activation experiments in rats. We isolated human PDLCs (hPDLCs) in vitro and evaluated the effects of LIPUS on the osteogenic differentiation of force-treated hPDLCs using real-time quantitative PCR, Western blot, alkaline phosphatase and alizarin red staining. Small interfering RNA and Yoda1 were employed to validate the role of Piezo1 in this process. Results: LIPUS promoted osteoclast differentiation and accelerated OTM in rats. Furthermore, LIPUS alleviated alveolar bone resorption under pressure and enhanced osteogenesis of force-treated PDLCs both in vivo and in vitro by downregulating Piezo1 expression. Subsequent administration of GsMTx4 in rats and siPIEZO1 transfection in hPDLCs attenuated the inhibitory effect on osteogenic differentiation under pressure, whereas LIPUS efficacy was partially mitigated. Yoda1 treatment inhibited osteogenic differentiation of hPDLCs, resulting in reduced expression of Collagen Ⅰα1 and osteocalcin in the periodontal ligament. However, LIPUS administration was able to counteract these effects. Conclusion: This research unveils that LIPUS promotes the osteogenesis of force-treated PDLCs via downregulating Piezo1.

Effectiveness of low-intensity pulsed ultrasound on osteoarthritis: molecular mechanism and tissue engineering.

Osteoarthritis (OA) is distinguished by pathological alterations in the synovial membrane, articular cartilage, and subchondral bone, resulting in physical symptoms such as pain, deformity, and impaired mobility. Numerous research studies have validated the effectiveness of low-intensity pulsed ultrasound (LIPUS) in OA treatment. The periodic mechanical waves generated by LIPUS can mitigate cellular ischemia and hypoxia, induce vibration and collision, produce notable thermal and non-thermal effects, alter cellular metabolism, expedite tissue repair, improve nutrient delivery, and accelerate the healing process of damaged tissues. The efficacy and specific mechanism of LIPUS is currently under investigation. This review provides an overview of LIPUS's potential role in the treatment of OA, considering various perspectives such as the synovial membrane, cartilage, subchondral bone, and tissue engineering. It aims to facilitate interdisciplinary scientific research and further exploration of LIPUS as a complementary technique to existing methods or surgery. Ongoing research is focused on determining the optimal dosage, frequency, timing, and treatment strategy of LIPUS for OA. Additional research is required to clarify the precise mechanism of action and potential impacts on cellular, animal, and human systems prior to its integration into therapeutic applications.

Development of an ultrasound-mediated nano-sized drug-delivery system for cancer treatment: from theory to experiment.

Aim: To establish a methodology for understanding how ultrasound (US) induces drug release from nano-sized drug-delivery systems (NSDDSs) and enhances drug penetration and uptake in tumors. This aims to advance cancer treatment strategies. Materials & methods: We developed a multi-physics mathematical model to elucidate and understand the intricate mechanisms governing drug release, transport and delivery. Unique in vitro models (monolayer, multilayer, spheroid) and a tailored US exposure setup were introduced to evaluate drug penetration and uptake. Results: The results highlight the potential advantages of US-mediated NSDDSs over conventional NSDDSs and chemotherapy, notably in enhancing drug release and inducing cell death. Conclusion: Our sophisticated numerical and experimental methods aid in determining and quantifying drug penetration and uptake into solid tumors.

Effect of Low-Intensity Pulsed Ultrasound on Macrophage Properties and Fibrosis in the Infrapatellar Fat Pad in a Carrageenan-Induced Knee Osteoarthritis Rat Model.

BACKGROUND: In the progression of knee osteoarthritis (KOA), fibrosis of the infrapatellar fat pad (IFP) is a key pathological change. Low-intensity pulsed ultrasound (LIPUS) inhibits IFP fibrosis by decreasing the gene expression and activity of hypoxia-inducible factor (HIF-1α), which is a protein involved in IFP fibrosis in KOA rat models. On the other hand, macrophages play an important role in the progression of fibrosis in various tissues, and LIPUS irradiation suppresses macrophage infiltration and inflammatory cytokine secretion. However, whether LIPUS suppresses macrophage polarity and IFP fibrosis in KOA remains unclear. Therefore, we investigated the effect of LIPUS on macrophage polarity and IFP fibrosis. MATERIALS AND METHODS: A KOA model was created by injecting carrageenin into the bilateral knee joints of Wistar rats (eight weeks old). Tissues were harvested over time for histological and molecular biological analysis. The KOA model was also subjected to LIPUS irradiation for two weeks following the injection of carrageenin. RESULTS: RM-4-positive cells were widely distributed in IFP two weeks after carrageenin administration, but M2 macrophages were significantly increased, and the Sirius red area was decreased in the LIPUS-irradiated group compared with those in the non-irradiated group. The gene expression of M1 macrophage markers was significantly decreased and that of M2 macrophage markers was significantly increased in the LIPUS-irradiated group. The expression of transforming growth factor-ß (TGF-ß) and type 1 collagen was also significantly decreased. CONCLUSION: These results suggest that LIPUS may serve as a novel approach for the treatment of KOA through its effect on M1 macrophages and suppression of TGF-ß expression.

Optimal treatment conditions for low-intensity pulsed ultrasound therapy for Alzheimer's disease: applications from mice to humans.

PURPOSE: We previously developed a novel therapy with low-intensity pulsed ultrasound (LIPUS) that ameliorates cognitive decline through upregulation of endothelial nitric oxide synthase (eNOS) in mouse models of Alzheimer's disease (AD). In a randomized, double-blind, placebo-controlled pilot trial, we demonstrated that whole-brain LIPUS therapy is safe and tends to suppress the cognitive decline in early AD patients. We herein report the findings of our basic experiments that we performed for the pilot trial in order to apply whole-brain LIPUS therapy to humans, as well. METHODS: First, we examined the relationship between bone density/thickness and ultrasound transmittance using human temporal bone. Next, based on the results of ultrasound transmittance, we further examined mRNA expression of VEGF, FGF2, and eNOS in response to variable ultrasound frequencies, duty cycles, and sound pressures. RESULTS: There was a significant correlation between bone thickness and transmittance (1.0 MHz, P < 0.001), while there was no significant correlation between bone density and transmittance (1.0 MHz, P = 0.421). At a frequency of 0.5 MHz, the optimum duty cycle was considered to be up to 20%. When the tissue amplitude was in the range of 0.05-0.5 MPa, VEGF, FGF2, and eNOS were significantly upregulated by LIPUS. Thus, the conditions necessary for LIPUS therapy for the human brain were identified as sound pressure just below the probe 1.3 MPa (tissue amplitude 0.15 MPa), duty cycle 5%, and frequency 0.5 MHz. CONCLUSION: We successfully identified the optimal treatment conditions for LIPUS therapy for patients with AD.

Low-intensity pulsed ultrasound reduces alveolar bone resorption during orthodontic treatment via Lamin A/C-Yes-associated protein axis in stem cells.

BACKGROUND: The bone remodeling during orthodontic treatment for malocclusion often requires a long duration of around two to three years, which also may lead to some complications such as alveolar bone resorption or tooth root resorption. Low-intensity pulsed ultrasound (LIPUS), a noninvasive physical therapy, has been shown to promote bone fracture healing. It is also reported that LIPUS could reduce the duration of orthodontic treatment; however, how LIPUS regulates the bone metabolism during the orthodontic treatment process is still unclear. AIM: To investigate the effects of LIPUS on bone remodeling in an orthodontic tooth movement (OTM) model and explore the underlying mechanisms. METHODS: A rat model of OTM was established, and alveolar bone remodeling and tooth movement rate were evaluated via micro-computed tomography and staining of tissue sections. In vitro, human bone marrow mesenchymal stem cells (hBMSCs) were isolated to detect their osteogenic differentiation potential under compression and LIPUS stimulation by quantitative reverse transcription-polymerase chain reaction, Western blot, alkaline phosphatase (ALP) staining, and Alizarin red staining. The expression of Yes-associated protein (YAP1), the actin cytoskeleton, and the Lamin A/C nucleoskeleton were detected with or without YAP1 small interfering RNA (siRNA) application via immunofluorescence. RESULTS: The force treatment inhibited the osteogenic differentiation potential of hBMSCs; moreover, the expression of osteogenesis markers, such as type 1 collagen (COL1), runt-related transcription factor 2, ALP, and osteocalcin (OCN), decreased. LIPUS could rescue the osteogenic differentiation of hBMSCs with increased expression of osteogenic marker inhibited by force. Mechanically, the expression of LaminA/C, F-actin, and YAP1 was downregulated after force treatment, which could be rescued by LIPUS. Moreover, the osteogenic differentiation of hBMSCs increased by LIPUS could be attenuated by YAP siRNA treatment. Consistently, LIPUS increased alveolar bone density and decreased vertical bone absorption in vivo. The decreased expression of COL1, OCN, and YAP1 on the compression side of the alveolar bone was partially rescued by LIPUS. CONCLUSION: LIPUS can accelerate tooth movement and reduce alveolar bone resorption by modulating the cytoskeleton-Lamin A/C-YAP axis, which may be a promising strategy to reduce the orthodontic treatment process.

Long-pulsed ultrasound-mediated microbubble thrombolysis in a rat model of microvascular obstruction.

In up to 30% patients who experience acute myocardial infarction, successful recanalization of the epicardial coronary artery cannot provide adequate microvascular reperfusion. In this study, we sought to determine whether long-pulsed ultrasound (US)-mediated microbubble (MB) cavitation was useful for the treatment of microvascular obstruction, and the therapeutic effects were compared within different long-pulse-length and short-pulsed US. Microvascular obstruction model was established by injecting micro-thrombi into common iliac artery of a rat's hind limb. About 1 MHz US with different long pulse lengths (ranging from 100 to 50,000 cycles) was delivered, compared to short pulse (5 cycles). The control group was given MB only without therapeutic US. Contrast perfusion images were performed at baseline, emboli, and 1, 5, 10 min post-embolization, and peak plateau video intensity (A) was obtained to evaluate the therapeutic effects. Long-tone-burst US showed better thrombolytic effects than short-pulsed US (1,000, 5,000 cycles >500 cycles, >5 cycles, and control) (P < 0.01). 1,000 cycles group showed the optimal thrombolytic effect, but microvascular hemorrhage was observed in 50,000 cycles group. In conclusion, long-tone-burst US-enhanced MB therapy mediated successful thrombolysis and may offer a powerful approach for the treatment for microvascular obstruction within a certain pulse length.

The Effect of Low-Intensity Pulsed Ultrasound on Bone Regeneration and the Expression of Osterix and Cyclooxygenase-2 during Critical-Size Bone Defect Repair.

Low-intensity pulsed ultrasound (LIPUS) is a form of ultrasound that utilizes low-intensity pulsed waves. Its effect on bones that heal by intramembranous ossification has not been sufficiently investigated. In this study, we examined LIPUS and the autologous bone, to determine their effect on the healing of the critical-size bone defect (CSBD) of the rat calvaria. The bone samples underwent histological, histomorphometric and immunohistochemical analyses. Both LIPUS and autologous bone promoted osteogenesis, leading to almost complete closure of the bone defect. On day 30, the bone volume was the highest in the autologous bone group (20.35%), followed by the LIPUS group (19.12%), and the lowest value was in the control group (5.11%). The autologous bone group exhibited the highest intensities of COX-2 (167.7 ± 1.1) and Osx (177.1 ± 0.9) expression on day 30. In the LIPUS group, the highest intensity of COX-2 expression was found on day 7 (169.7 ±1.6) and day 15 (92.7 ± 2.2), while the highest Osx expression was on day 7 (131.9 ± 0.9). In conclusion, this study suggests that LIPUS could represent a viable alternative to autologous bone grafts in repairing bone defects that are ossified by intramembranous ossification.

Efficacy of Wearable low-intensity pulsed Ultrasound treatment in the Movement disorder in Parkinson's disease (the SWUMP trial): protocol for a single-site, double-blind, randomized controlled trial.

BACKGROUND: Parkinson's disease (PD) is a progressive, neurodegenerative illness marked by the loss of dopaminergic neurons, causing motor symptoms. Oral levodopa replacement therapy remains the gold standard in the treatment of PD. It is, nevertheless, a symptomatic treatment. There is currently no effective treatment for PD. Therefore, new therapies for PD are highly desirable. Low-intensity pulsed ultrasound (LIPUS) has been shown to improve behavioral functions in PD animal models. It is a new type of neuromodulation approach that combines noninvasiveness with high spatial precision. The purpose of this study is to establish a new clinical protocol for LIPUS in the treatment of movement disorders in patients with PD. METHODS: This protocol is a single-site, prospective, double-blind, randomized controlled trial (RCT). Forty-eight participants with clinically confirmed PD will be randomly allocated to one of two groups: LIPUS group or sham group. All of the participants continue to use pharmacological therapy as a fundamental treatment. The primary outcome is the difference between groups from baseline to 4 months in the change in the Unified Parkinson's Disease Rating Scale (UPDRS) motor score (part III). The secondary outcomes include the rating scales such as the Mini-Mental State Examination (MMSE), and other three rating scales, and medical examinations including high-density electroencephalography (hdEEG) and functional magnetic resonance imaging (fMRI). The primary safety outcome will be assessed at 4 months, and adverse events will be recorded. DISCUSSION: This study represents the clinical investigation into the efficacy of therapeutic LIPUS in the treatment of PD for the first time. If LIPUS is determined to be effective, it could offer a practical and innovative means of expanding the accessibility of ultrasound therapy by using a wearable LIPUS device within a home setting. TRIAL REGISTRATION: Chinese Clinical Trial Registry ChiCTR2100052093. Registered on 17 October 2021.

Effects of Low-Intensity Pulsed Ultrasound on the Regulation of Free Fatty Acid Release in 3T3-L1 Cells.

OBJECTIVES: To investigate the effects of low-intensity pulsed ultrasound (LIPUS) on the proliferation, differentiation, and tumor necrosis factor-α (TNF-α)-induced lipolysis of 3T3-L1 cells, and to explore the feasibility of regulating the release of free fatty acids (FFA) to prevent lipotoxicity. METHODS: Different intensities (30, 60, 90, and 120 mW/cm2) of LIPUS were applied to 3T3-L1 preadipocytes for different durations (5, 10, 15, 20, 25, and 30 minutes). Appropriate parameters for subsequent experiments were selected by assessing cell viability. The effect of LIPUS on the proliferation and differentiation of 3T3-L1 cells was evaluated by microscope observation, flow cytometry, and lipid content determination. After treated with LIPUS and TNF-α (50 ng/mL), the degree of lipolysis was assessed by measuring the extracellular FFA content. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to detect the mRNA expression of relevant genes. RESULTS: Different parameters of LIPUS significantly enhance the viability of 3T3-L1 cells (P < .05), with 20 minutes and 30 mW/cm2 as the most suitable settings. After LIPUS treatment, 3T3-L1 cell proliferation accelerated, apoptosis rate and G1 phase cell proportion decreased, the content of lipid droplets and TG was increased in differentiated cells, while FFA release decreased (P < .05). The expression of PCNA, PPARγ, C/EBPα, Perilipin A mRNA increased, and the expression of TNF-α, ATGL, HSL mRNA decreased (P < .05). CONCLUSIONS: LIPUS could promote the proliferation and differentiation of 3T3-L1 cells and inhibit TNF-α-induced lipolysis, indicating its potential as a therapy for mitigating lipotoxicity caused by decompensated adipocytes.