Efectividad del ultrasonido pulsado de baja intensidad en pacientes tras osteotomía: una revisión sistemática / Effectiveness of low-intensity pulsed ultrasound in patients after osteotomy: A systematic review

La utilización de la terapia de ultrasonidos pulsados de baja intensidad para la cicatrización ósea y el tratamiento de fracturas es considerada cada vez más como una alternativa terapéutica de coste económico moderado y con efectos adversos nulos o mínimos (p. ej. leve reacción al gel conductor).Con todo, existe cierta controversia con relación a su evidencia científica. La presente revisión busca arrojar algo de luz sobre esta controversia y cubrir un espacio de estudio no ocupado por trabajos previos ni actuales sobre la terapia mediante ultrasonidos. Es necesario conocer el impacto real del tratamiento con ultrasonidos pulsados de baja intensidad en pacientes sometidos a osteotomía, así como su aplicabilidad como protocolo poscirugía para mejorar los procesos de recuperación, rehabilitación y, con ello, disminuir los tiempos de incapacidad. (AU)

The use of low intensity pulsed ultrasound (LIPUS) therapy for bone healing and fracture treatment is increasingly considered as a therapeutic alternative with moderate economic cost and none or minimal adverse effects (e.g., low reaction to the conductive gel).However, there is some controversy regarding its scientific evidence. The present review seeks to shed some light on this controversy and to cover an area of study not occupied by previous or current work on ultrasound therapy. It is necessary to know the real impact of the treatment with low intensity pulsed ultrasound in patients with osteotomy, as well as its applicability as a post-surgery protocol to improve the recovery and rehabilitation processes and, at the end of the day, to reduce the time of disability. (AU)

NR1I2 as a core biological target in chronic venous ulcer tissues treated with ultrasound therapy.

Ultrasound therapy is a method of applying ultrasonic energy to the stimulation produced by human body to change the function and tissue state of the body in order to achieve the purpose of treating diseases. Chronic venous ulcer is a common chronic skin ulcer. GSE222503 for ultrasound therapy of chronic venous ulcers was downloaded from gene expression omnibus database, which were used to identify differentially expressed genes. Weighted gene co-expression network analysis, functional enrichment analysis, gene set enrichment analysis, immune infiltration analysis and construction and analysis of protein-protein interaction network were performed. Draw gene expression heatmaps. Comparative toxicogenomics database analysis was performed. Two hundred thirty-five differentially expressed genes were obtained. According to gene ontology analysis, in biological process analysis, they were mainly enriched in positive regulation of cellular biosynthetic process, reproductive cell development, vasculogenesis, vascular morphogenesis, and inflammatory response. In cellular component analysis, they were mainly enriched in leading edge of growing cell, extracellular matrix binding organelle, F-actin capping protein complex. In molecular function analysis, they were mainly concentrated in receptor ligand activity, cytokine receptor binding. In Kyoto encyclopedia of genes and genomes analysis, they were mainly enriched in cytokine-cytokine receptor interaction, PI3K-Akt signaling pathway, HIF-1 signaling pathway, heme biosynthesis. In weighted gene co-expression network analysis, the soft threshold power was set to 9. Thirty modules were generated. PF4, NR1I2, TTC16, H3C12, KLRB1, CYP21A2 identified by 4 algorithms (MCC, EPC, closeness, stress). Heatmap of core gene expression showed that H3C12, KLRB1, PF4, NR1I2 were all underexpressed in samples of ultrasound-treated chronic venous ulcers and overexpressed in samples of untreated chronic venous ulcers. Comparative toxicogenomics database analysis showed that H3C12, KLRB1, PF4, NR1I2 are associated with thrombophlebitis, phlebitis, vascular malformations, metabolic syndrome, ulcers, and inflammation. In samples of chronic venous ulcer tissue treated with ultrasound, NR1I2 shows low expression, while in samples of chronic venous ulcer tissue without ultrasound treatment, it shows high expression. This finding suggests a potential role of NR1I2 in the process of ultrasound therapy for chronic venous ulcers, which may be related to the therapeutic effect of ultrasound therapy on chronic venous ulcers.

Efficacy and safety of ultrasound-assisted wound debridement in the treatment of diabetic foot ulcers: a systematic review and meta-analysis of 11 randomized controlled trials.

Objective: Research data suggests that ultrasound-assisted wound debridement (UAWD) can effectively promote the healing of diabetic foot ulcers (DFU). However, existing research is not consistent with this viewpoint. Therefore, we conducted this study to investigate the effect of UAWD on the healing of diabetic foot ulcers. Methods: From the establishment of the database to January 2024, we searched 8 databases to study the effectiveness and safety of UAWD in the treatment of DFU. Two authors independently screened the qualifications of the articles, while two authors extracted relevant data. Statistical analysis was conducted using Review Manager 5.4 and STATA 18.0 software. Results: A total of 11 randomized controlled studies were included, with 6 countries and 696 participants participating. Our findings showed that UAWD was associated with a significant benefit in healing rate (OR = 2.60, 95% CI: [1.67, 4.03], P < 0.0001, I2 = 25%), wound healing time (MD = -11.94, 95% CI: [-23.65, -0.23], P = 0.05, I2 = 99%), percentage reduction in wound size (MD = 14.2, 95% CI: [10.8, 17.6], P = 0.47, I2 = 32%), effectiveness of treatment (OR = 10.3, 95% CI: [4.68, 22.66], P < 0.00001, I2 = 0%). Moreover, UAWD did not cause any significant adverse reactions. However, there was no obvious difference in wound blood perfusion (MD = 0.25, 95% CI: [-0.01, 0.52], P = 0.06, I2 = 90%), transcutaneous oxygen partial pressure (MD = 14.34, 95% CI: [-10.03, 38.71], P = 0.25, I2 = 98%). Conclusion: UAWD can significantly improve wound healing rate, shorten wound healing time, accelerate wound area reduction, and improve clinical treatment effectiveness without significant adverse reactions. Although there is no significant difference in transcutaneous oxygen pressure and wound blood flow perfusion between UAWD and SWC. So we look forward to more scientifically blinded, placebo-controlled, high-quality studies in the future, to enable researchers to obtain more complete and accurate analytical data, in order to improve the scientific and credibility of the evidence. Systematic review registration: https://www.crd.york.ac.uk/prospero/, identifier CRD42024501198.

In-vitro effects of novel periodontal scalers with a planar ultrasonic piezoelectric transducer on periodontal biofilm removal, dentine surface roughness, and periodontal ligament fibroblasts adhesion.

OBJECTIVES: To compare ultrasonic scaler prototypes based on a planar piezoelectric transducer with different working frequencies featuring a titanium (Ti-20, Ti-28, and Ti-40) or stainless steel (SS-28) instrument, with a commercially available scaler (com-29) in terms of biofilm removal and reformation, dentine surface roughness and adhesion of periodontal fibroblasts. MATERIALS AND METHODS: A periodontal multi-species biofilm was formed on specimens with dentine slices. Thereafter specimens were instrumented with scalers in a periodontal pocket model or left untreated (control). The remaining biofilms were quantified and allowed to reform on instrumented dentine slices. In addition, fibroblasts were seeded for attachment evaluation after 72 h of incubation. Dentine surface roughness was analyzed before and after instrumentation. RESULTS: All tested instruments reduced the colony-forming unit (cfu) counts by about 3 to 4 log10 and the biofilm quantity (each p < 0.01 vs. control), but with no statistically significant difference between the instrumented groups. After 24-hour biofilm reformation, no differences in cfu counts were observed between any groups, but the biofilm quantity was about 50% in all instrumented groups compared to the control. The attachment of fibroblasts on instrumented dentine was significantly higher than on untreated dentine (p < 0.05), with the exception of Ti-20. The dentine surface roughness was not affected by any instrumentation. CONCLUSIONS: The planar piezoelectric scaler prototypes are able to efficiently remove biofilm without dentine surface alterations, regardless of the operating frequency or instrument material. CLINICAL RELEVANCE: Ultrasonic scalers based on a planar piezoelectric transducer might be an alternative to currently available ultrasonic scalers.

Noninvasive release of tendons using MRI guided focused ultrasound: a hybrid therapy using long-pulse focused ultrasound followed by thermal ablation.

INTRODUCTION: Magnetic Resonance-guided Focused Ultrasound (MRgFUS) thermal ablation is an effective noninvasive ultrasonic therapy to disrupt in vivo porcine tendon but is prone to inducing skin burns. We evaluated the safety profile of a novel hybrid protocol that minimizes thermal spread by combining long-pulse focused ultrasound followed by thermal ablation. METHODS: In-vivo Achilles tendons (hybrid N = 15, thermal ablation alone N = 21) from 15 to 20 kg Yorkshire pigs were randomly assigned to 6 treatment groups in two studies. The first (N = 21) was ablation (600, 900, or 1200 J). The second (N = 15) was hybrid: pulsed FUS (13.5 MPa peak negative pressure) followed by ablation (600, 900, or 1200 J). Measurements of ankle range of motion, tendon temperature, thermal dose (240 CEM43), and assessment of skin burn were performed in both groups. RESULTS: Rupture was comparable between the two protocols: 1/5 (20%), 5/5 (100%) and 5/5 (100%) for hybrid protocol, compared to 2/7 (29%), 6/7 (86%) and 7/7 (100%) for the ablation-only protocol with energies of 600, 900, and 1200 J, respectively. The hybrid protocol produced lower maximum temperatures, smaller areas of thermal dose, fewer thermal injuries to the skin, and fewer full-thickness skin burns. The standard deviation for the area of thermal injury was also smaller for the hybrid protocol, suggesting greater predictability. CONCLUSION: This study demonstrated a hybrid MRgFUS protocol combining long-pulse FUS followed by thermal ablation to be noninferior and safer than an ablation-only protocol for extracorporeal in-vivo tendon rupture for future clinical application for noninvasive release of contracted tendon.

Comparing the Safety and Effectiveness of Microfocused Ultrasound: Standard vs Targeted Tissue Protocol in Lifting and Tightening the Lower Face and Upper Neck.

BACKGROUND: Micro-focused ultrasound with visualization (MFU-V) delivers energy to specific soft tissue layers beneath the epidermis with the ability to lift and tighten the lower face and neck.  Objective: To determine the efficacy of microfocused ultrasound with visualization (MFU-V) using a standard treatment line protocol versus a customized treatment line protocol based on the patient's unique anatomy targeting the superficial muscular aponeurotic system and fibrous septae for lifting and tightening of the lower face and neck. METHODS: This was a single-center, prospective, randomized, investigator-blinded clinical trial. 51 subjects were randomized to receive a single treatment of MFU-V targeting the lower face and neck using either a standard or custom treatment protocol.   Results: Subjects in both standard and custom treatment groups noted a greater than one-point improvement in jawline laxity. Three-dimensional photography measurements also demonstrated lifting of the lower face and neck in both treatment groups. CONCLUSION: Custom and standard treatment MFU-V protocols produce a safe and effective treatment for tightening and lifting the lower face and neck. Custom treatment protocols aid in maximizing results for patients with variations in the anatomy of the lower face and neck.  J Drugs Dermatol. 2024;23(4):7647.     doi:10.36849/JDD.7647.

Comparative Study of Sonodynamic and Photoactivated Cancer Therapies with Re(I)-Tricarbonyl Complexes Comprising Phenanthroline Ligands.

Herein, we have compared the effectivity of light-based photoactivated cancer therapy and ultrasound-based sonodynamic therapy with Re(I)-tricarbonyl complexes (Re1-Re3) against cancer cells. The observed photophysical and TD-DFT calculations indicated the potential of Re1-Re3 to act as good anticancer agents under visible light/ultrasound exposure. Re1 did not display any dark- or light- or ultrasound-triggered anticancer activity. However, Re2 and Re3 displayed concentration-dependent anticancer activity upon light and ultrasound exposure. Interestingly, Re3 produced 1O2 and OH• on light/ultrasound exposure. Moreover, Re3 induced NADH photo-oxidation in PBS and produced H2O2. To the best of our knowledge, NADH photo-oxidation has been achieved here with the Re(I) complex for the first time in PBS. Additionally, Re3 released CO upon light/ultrasound exposure. The cell death mechanism revealed that Re3 produced an apoptotic cell death response in HeLa cells via ROS generation. Interestingly, Re3 showed slightly better anticancer activity under light exposure compared to ultrasound exposure.

Current clinical investigations of focused ultrasound blood-brain barrier disruption: A review.

The blood-brain barrier (BBB) presents a formidable challenge in delivering therapeutic agents to the central nervous system. Ultrasound-mediated BBB disruption has emerged as a promising non-invasive technique to enhance drug delivery to the brain. This manuscript reviews fundamental principles of ultrasound-based techniques and their mechanisms of action in temporarily permeabilizing the BBB. Clinical trials employing ultrasound for BBB disruption are discussed, summarizing diverse applications ranging from the treatment of neurodegenerative diseases to targeted drug delivery for brain tumors. The review also addresses safety considerations, outlining the current understanding of potential risks and mitigation strategies associated with ultrasound exposure, including real-time monitoring and assessment of treatment efficacy. Among the large number of studies, significant successes are highlighted thus providing perspective on the future direction of the field.

Hybrid Sono-Photodynamic Combination Therapy Mediated by Water-Soluble Gallium Phthalocyanine Enhances the Cytotoxic Effect against Breast Cancer Cell Lines.

Breast cancer is a life-threatening disease that is gaining increasing importance due to its rising incidence, highlighting the need for novel treatment methods with the least disadvantages. Recently, scientists have focused on developing therapeutic treatment modalities for effective cancer treatment. In contrast to conventional cancer treatment methods such as immunotherapy, surgery, chemotherapy, or radiotherapy, photodynamic therapy (PDT) is gaining prominence. Besides, sonodynamic treatment (SDT) is a noninvasive therapeutic approach that uses ultrasound to induce high tissue penetration. In both methods, sensitizers are activated to generate cytotoxic reactive oxygen species such as •OH and 1O2. In particular, the combined use of hybrid and complementary treatment methods has become an important modality in cancer treatment in recent years. Sono-photodynamic therapy (SPDT), which is an important method applied in combination with PDT and SDT, has started to be preferred in terms of reducing potential side effects compared to monotherapy. One of the most important types of sensitizers used in PDT and SDT is known as phthalocyanines (Pcs). Motivated by these facts, this research presents the sono-photochemical, in vitro cytotoxicity, and theoretical evaluation of water-soluble gallium phthalocyanine (GaPc). The results indicate that the quantum yield of the generation of singlet oxygen increased in sono-photochemical studies (ΦΔ = 0.94), compared to photochemical studies (ΦΔ = 0.72). In vitro analyses revealed that GaPc did not exhibit significant cytotoxic effects at the specified varying concentration doses (1-20 µM). Furthermore, GaPc-mediated SPDT triggered cell death by inducing reactive oxygen species formation in the breast cancer cell line (MCF-7). The interaction mechanism of the GaPc with EGFR and VEGFR2 target proteins, which are critical regulators of metastasis, proliferation, and angiogenesis, was investigated by molecular docking simulation. GaPc has effective binding affinities against target proteins, and this affinity was found to be the highest against VEGFR2. Molecular docking results showed a good correlation with the obtained biological results. Eventually, this molecular building of the efficient water-soluble phthalocyanine-based sensitizer is a potential therapeutic for PDT, SDT, and SPDT applications.

Does Full-Mouth Disinfection Influence the Size of the Periodontal Inflammatory Burden and the Level of hsCRP?

PURPOSE: To investigate the effect of full-mouth disinfection on the sizes of the periodontal wound and periodontal inflammatory burden and whether it leads to a decrease in C-reactive protein (CRP) levels. MATERIALS AND METHODS: The study included 20 systemically healthy subjects (11 women and 9 men) 30 to 68 years old with localised or generalised periodontitis (stage III, grade C). The sizes of the periodontal wound and periodontal inflammatory burden were measured with the web application "Periodontalwound", which is based on measurements of average tooth cervices, as well as probing depths and bleeding on probing assessed at six sites around each tooth present in the oral cavity. The levels of hsCRP (high-sensitivity CRP) were measured with an immunochemical method. All three parameters were measured before initial treatment and 3 months after therapy. Full-mouth disinfection included removal of plaque and calculus with ultrasonic and hand instruments in one session. RESULTS: The results showed a statistically significant decrease in the size of the periodontal wound (p < 0.001), a statistically significant decrease in the size of periodontal inflammatory burden (p < 0.001), and a decrease in hsCRP levels 3 months after therapy. CONCLUSION: Full-mouth disinfection leads to a decrease in the periodontal wound and periodontal inflammatory burden size, as well as a decrease in the levels of hsCRP in patients with localised or generalised periodontitis (stage III, grade C).

Bioactive Layered Double Hydroxides for Synergistic Sonodynamic/Cuproptosis Anticancer Therapy with Elicitation of the Immune Response.

Sonodynamic therapy (SDT) has promising application prospects in tumor therapy. However, SDT does not eradicate metastatic tumors. Herein, Cu-substituted ZnAl ternary layered double hydroxide nanosheets (ZCA NSs) were developed as both sonosensitizers and copper nanocarriers for synergistic SDT/cuproptosis cancer therapy. An optimized electronic structure more conducive to the sonodynamic process was obtained from ZCA NSs via the Jahn-Teller effect induced by the introduction of Cu2+, and the synthesized ZCA NSs regulated the intricate tumor microenvironment (TME) by depleting endogenous glutathione (GSH) to amplify oxidative stress for further enhanced SDT performance. Furthermore, cuproptosis was evoked by intracellular overload of Cu2+ and amplified by SDT, leading to irreversible proteotoxicity. In vitro results showed that such synergetic SDT/cuproptosis triggered immunogenic cell death (ICD) and promoted the maturation of dendritic cells (DCs). Furthermore, the as-synthesized ZCA NS-mediated SDT/cuproptosis thoroughly eradicated the in vivo solid tumors and simultaneously elicited antitumor immunity to suppress lung and liver metastasis. Overall, this work established a nanoplatform for synergistic SDT/cuproptosis with a satisfactory antitumor immunity.

Concern about the risk of aerosol contamination from ultrasonic scaler: a systematic review and meta-analysis.

BACKGROUND: Many instruments used in dentistry are rotary, such as handpieces, water syringes, and ultrasonic scalers that produce aerosols. The spray created by these instruments can carry, in addition to water, droplets of saliva, blood, and microorganisms, which can pose a risk of infections for healthcare professionals and patients. Due to the COVID-19 pandemic, this gained attention. OBJECTIVE: The aim was to carry out a systematic review of the evidence of the scope of the aerosol produced by ultrasonic scaler in environmental contamination and the influence of the use of intraoral suction reduction devices. DESIGN: Scientific literature was searched until June 19, 2021 in 6 databases: Pubmed, EMBASE, Web of science, Scopus, Virtual Health Library and Cochrane Library, without restrictions on language or publication date. Studies that evaluated the range of the aerosol produced by ultrasonic scaler during scaling/prophylaxis and the control of environmental contamination generated by it with the use of low (LVE) and high (HVE) volume evacuation systems were included. RESULTS: Of the 1893 potentially relevant articles, 5 of which were randomized controlled trials (RCTs). The meta-analysis of 3 RCTs showed that, even at different distances from the patient's oral cavity, there was a significant increase in airborne bacteria in the dental environment with the use of ultrasonic scaler. In contrast, when meta-analysis compared the use of HVE with LVE, there was no significant difference (P = 0.40/CI -0.71[-2.37, 0.95]) for aerosol produced in the environment. CONCLUSIONS: There is an increase in the concentration of bioaerosol in the dental environment during the use of ultrasonic scaler in scaling/prophylaxis, reaching up to 2 m away from the patient's mouth and the use of LVE, HVE or a combination of different devices, can be effective in reducing air contamination in the dental environment, with no important difference between different types of suction devices.

Neuromodulatory Focused Ultrasound for Epilepsy: Are Animal Models Useful?

Ultrasound neuromodulation is a potential alternative therapy for suppressing epileptic discharges. Recently, several human clinical trials have reported promising results from repeated focused ultrasound (FUS) treatments for temporal lobe epilepsy. In this Viewpoint, we highlight the valuable guidance of preclinical validation methods for choosing the optimal FUS parameters, thus ensuring consistency with the outcomes of clinical trials and leading human trials to the safest and most effective approaches.

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.

The value of low-intensity pulsed ultrasound in reducing ovarian injury caused by chemotherapy in mice.

BACKGROUND: Ovarian damage and follicle loss are major side effects of chemotherapy in young female patients with cancer. However, effective strategies to prevent these injuries are still lacking. The purpose of this study was to verify low-intensity pulsed ultrasound (LIPUS) can reduce ovarian injury caused by chemotherapy and to explore its underlying mechanisms in mice model. METHODS: The mice were randomly divided into the Control group, Cisplatin group, and Cisplatin + LIPUS group. The Cisplatin group and Cisplatin + LIPUS group were intraperitoneally injected with cisplatin every other day for a total of 10 injections, and the Control group was injected with saline. On the second day of each injection, the Cisplatin + LIPUS group received irradiation, whereas the other two groups received sham irradiation. We used a variety of biotechnologies to detect the differences in follicle count, granulosa cell apoptosis, fibrosis, transcriptome level, oxidative damage, and inflammation in differently treated mice. RESULT: LIPUS was able to reduce primordial follicle pool depletion induced by cisplatin and inhibit the apoptosis of granulosa cells. Transcriptomic results confirmed that LIPUS can reduce ovarian tissue injury. We demonstrated that LIPUS can relieve ovarian fibrosis by inhibiting TGF-ß1/Smads pathway. Meanwhile, it can reduce the oxidative damage and reduced the mRNA levels of proinflammatory cytokines caused by chemotherapy. CONCLUSION: LIPUS can reduce the toxic effects of chemotherapy drugs on ovaries, inhibit ovarian fibrosis, reduce the inflammatory response, and redcue the oxidative damage, reduce follicle depletion and to maintain the number of follicle pools.

Defect-rich sonosensitizers based on CeO2 with Schottky heterojunctions for boosting sonodynamic/chemodynamic synergistic therapy.

Sonodynamic therapy (SDT) has been recognized as a promising treatment for cancer due to its advantages of superior specificity, non-invasiveness, and deep tissue penetration. However, the antitumor effect of SDT remains restricted by the limited generation of reactive oxygen species (ROS) due to the lack of highly efficient sonosensitizers. In this work, we developed the novel sonosensitizer Pt/CeO2-xSx by constructing oxygen defects through S doping and Pt loading in situ. Large amounts of oxygen defects have been obtained by S doping, endowing Pt/CeO2-xSx with the ability to suppress electron-hole recombination, further promoting ROS production. Moreover, the introduction of Pt nanoparticles can not only produce oxygen in situ for relieving hypoxia but also form a Schottky heterojunction with CeO2-xSx for further inhibiting electron-hole recombination. In addition, Pt/CeO2-xSx could effectively deplete overexpressed glutathione (GSH) via redox reactions, amplifying oxidative stress in the tumor microenvironment (TME). Combined with the excellent POD-mimetic activity, Pt/CeO2-xSx can achieve highly efficient synergistic therapy of SDT and chemodynamic therapy (CDT). All these findings demonstrated that Pt/CeO2-xSx has great potential for cancer therapy, and this work provides a promising direction for designing and constructing efficient sonosensitizers.

Orchestrating apoptosis and ferroptosis through enhanced sonodynamic therapy using amorphous UIO-66-CoOx.

The development of efficient and multifunctional sonosensitizers is crucial for enhancing the efficacy of sonodynamic therapy (SDT). Herein, we have successfully constructed a CoOx-loaded amorphous metal-organic framework (MOF) UIO-66 (A-UIO-66-CoOx) sonosensitizer with excellent catalase (CAT)- and glutathione-oxidase (GSH-OXD)-like activities. The A-UIO-66-CoOx exhibits a 2.6-fold increase in singlet oxygen (1O2) generation under ultrasound (US) exposure compared to crystalline UIO-66 sonosensitizer, which is attributed to its superior charge transfer efficiency and consistent oxygen (O2) supply. Additionally, the A-UIO-66-CoOx composite reduces the expression of glutathione peroxidase (GPX4) by depleting glutathione (GSH) through Co3+ and Co2+ valence changes. The high levels of highly cytotoxic 1O2 and deactivation of GPX4 can lead to lethal lipid peroxidation, resulting in concurrent apoptosis and ferroptosis. Both in vitro and vivo tumor models comprehensively confirmed the enhanced SDT antitumor effect using A-UIO-66-CoOx sonosensitizer. Overall, this study emphasizes the possibility of utilizing amorphization engineering to improve the effectiveness of MOFs-based sonosensitizers for combined cancer therapies.

Effect of low-intensity focused ultrasound therapy on postpartum uterine involution in puerperal women: A randomized controlled trial.

BACKGROUND: Short-term poor uterine involution manifests as uterine contraction weakness. This is one of the important causes of postpartum hemorrhage, posing a serious threat to the mother's life and safety. The study aims to investigate whether low-intensity focused ultrasound (LIFUS) can effectively shorten lochia duration, alleviate postpartum complications, and accelerate uterine involution compared with the sham treatment. METHODS: A multicenter, concealed, randomized, blinded, and sham-controlled clinical trial was conducted across three medical centers involving 176 subjects, utilizing a parallel group design. Enrollment occurred between October 2019 and September 2020, with a 42-day follow-up period. Participants meeting the inclusion and exclusion criteria based on normal prenatal examinations were randomly divided into the LIFUS group or the sham operation group via computer-generated randomization. Patients in the LIFUS group received usual care with the LIFUS protocol, wherein a LIFUS signal was transmitted to the uterine site through coupling gel, or sham treatment, where no low-intensity ultrasound signal output was emitted. The primary outcome, lochia duration, was assessed via weekly telephonic follow-ups post-discharge. The involution of the uterus, measured by uterine fundus height, served as the secondary outcome. RESULTS: Among the 256 subjects screened for eligibility, 176 subjects were enrolled and randomly assigned to either the LIFUS group (n = 88) or the Sham group (n = 88). Data on the height of the uterine fundus were obtained from all the patients, with 696 out of 704 measurements (99%) successfully recorded. Overall, a statistically significant difference was noted in time to lochia termination (hazard ratio: 2.65; 95% confidence interval [CI]: 1.82-3.85; P < 0.001). The decline in fundal height exhibited notable discrepancies between the two groups following the second treatment session (mean difference: -1.74; 95% CI: -1.23 to -2.25; P < 0.001) and the third treatment session (mean difference: -3.26; 95% CI: -2.74 to -3.78; P < 0.001) after delivery. None of the subjects had any adverse reactions, such as skin damage or allergies during the treatment. CONCLUSIONS: This study found that LIFUS treatment can promote uterine involution and abbreviate the duration of postpartum lochia. Ultrasound emerges as a safe and effective intervention, poised to address further clinical inquiries in the domain of postpartum rehabilitation.

Recent advances of ultrasound-responsive nanosystems in tumor immunotherapy.

Immunotherapy has revolutionized cancer treatment by boosting the immune system and preventing disease escape mechanisms. Despite its potential, challenges like limited response rates and adverse immune effects impede its widespread clinical adoption. Ultrasound (US), known for its safety and effectiveness in tumor diagnosis and therapy, has been shown to significantly enhance immunotherapy when used with nanosystems. High-intensity focused ultrasound (HIFU) can obliterate tumor cells and elicit immune reactions through the creation of immunogenic debris. Low-intensity focused ultrasound (LIFU) bolsters tumor immunosuppression and mitigates metastasis risk by concentrating dendritic cells. Ultrasonic cavitation (UC) produces microbubbles that can transport immune enhancers directly, thus strengthening the immune response and therapeutic impact. Sonodynamic therapy (SDT) merges nanotechnology with immunotherapy, using specialized sonosensitizers to kill cancer cells and stimulate immune responses, increasing treatment success. This review discusses the integration of ultrasound-responsive nanosystems in tumor immunotherapy, exploring future opportunities and current hurdles.

Ultrasound imaging guided targeted sonodynamic therapy enhanced by magnetophoretically controlled magnetic microbubbles.

Sonodynamic therapy (SDT) utilizes ultrasonic excitation of a sensitizer to generate reactive oxygen species (ROS) to destroy tumor. Two dimensional (2D) black phosphorus (BP) is an emerging sonosensitizer that can promote ROS production to be used in SDT but it alone lacks active targeting effect and showed low therapy efficiency. In this study, a stable dispersion of integrated micro-nanoplatform consisting of BP nanosheets loaded and Fe3O4 nanoparticles (NPs) connected microbubbles was introduced for ultrasound imaging guided and magnetic field directed precision SDT of breast cancer. The targeted ultrasound imaging at 18 MHz and efficient SDT effects at 1 MHz were demonstrated both in-vitro and in-vivo on the breast cancer. The magnetic microbubbles targeted deliver BP nanosheets to the tumor site under magnetic navigation and increased the uptake of BP nanosheets by inducing cavitation effect for increased cell membrane permeability via ultrasound targeted microbubble destruction (UTMD). The mechanism of SDT by magnetic black phosphorus microbubbles was proposed to be originated from the ROS triggered mitochondria mediated apoptosis by up-regulating the pro-apoptotic proteins while down-regulating the anti-apoptotic proteins. In conclusion, the ultrasound theranostic was realized via the magnetic black phosphorus microbubbles, which could realize targeting and catalytic sonodynamic therapy.