Self-Powered Electrical Bandage Based on Body-Coupled Energy Harvesting.

Self-powered electrical bandages (SEBs), integrated with wearable energy harvesters, can provide an effective and autonomous electrical stimulation (ES) solution for rapid and scarless wound healing. A continuously operating, wireless, and applicable-to-comprehensive-wound ES device is essential for the quick restoration of wounds and convenience. This work illustrates a SEB powered by body-coupled energy harvesting. The SEB continuously treats the wound with 60-Hz sinusoidal electrical potential gained from the coupling of the human body and ambient electrical waves. It is demonstrated that enough level of electrical potential can be applied to the wound, further enhanced by strong capacitive coupling arising from the use of high-permittivity poly(vinylidene fluoride-trifluoroethylene):CaCu3Ti4O12 (P(VDF-TrFE):CCTO) nanocomposite. The potential clinical efficacy of the SEB is illustrated by preclinical analysis of human fibroblasts and mouse wound model, thus confirming the successful expedition of wound recovery. This work suggests a new class of wearable devices to provide ES events and its potential for extension to other conventional wound care materials and device technology.

Severe COVID-19 post pregnancy complicated by acute thromboemboli resulting in ST-elevation myocardial infarction - A case report.

Introduction: It has been shown that pregnancy can cause alterations in the severity of COVID-19 infection. We demonstrate an immediate post-partum patient diagnosed with severe COVID-19 and subsequently developed acute thrombosis of coronary artery.Case Summary: 35-year-old female unvaccinated for COVID-19 presented in labor and delivered on the same day. Several hours later, she was found to be in respiratory distress and tested positive for COVID-19. On day 7, computerized tomography (CT) of chest revealed bilateral pneumonia and pneumomediastinum. On day 8, she developed chest pain with electrocardiogram (EKG) showing inferior STelevations with troponin I of 0.6 ng/mL. She was intubated for airway protection and emergent diagnostic angiogram revealed thrombus occlusion of the third right posterolateral segment that resulted in thrombolysis in myocardial infarction (TIMI) 0 flow without evidence of underlying atherosclerotic disease in the remaining vessels. Intracoronary IIb/IIIa inhibitor was administered. Arterial blood gas in the lab revealed profound hypoxia despite being on 100% inspired oxygen. Multidisciplinary decision was made to cannulate patient for venovenous extracorporeal membrane oxygenation (ECMO) to treat severe COVID-19 pneumonia. She was finally decannulated from ECMO on day 65. After prolonged hospital stay, she eventually recovered and was discharged to rehabilitation.Conclusions: The center for disease control (CDC) surveillance has reported that pregnant patients with COVID-19 are more likely to require invasive ventilation and ECMO, and die given the immunological changes during pregnancy. Hypercoagulable state caused by combination of pregnancy and COVID-19 resulting in coronary thrombosis is rarely described in literature, our case demonstrated the paucity of this phenomenon.

High-Performing and Capacitive-Matched Triboelectric Implants Driven by Ultrasound.

In implantable bioelectronics, which aim for semipermanent use of devices, biosafe energy sources and packaging materials to protect devices are essential elements. However, research so far has been conducted in a direction where they cannot coexist. Here, the development of capacitance-matched triboelectric implants driven is reported by ultrasound under 500 mW cm-2 safe intensity and realize a battery-free, miniatured, and wireless neurostimulator with full titanium (Ti) packaging. The triboelectric implant with high dielectric composite, which has ultralow output impedance, can efficiently deliver sufficient power to generate the stimulation pulse without an energy-storing battery, despite ultrasound attenuation due to the Ti, and has the highest energy transmission efficiency among those reported so far. In vivo study using a rat model demonstrated that the proposed device system is an effective solution for relieving urinary symptoms. These achievements provide a significant step toward permanently implantable devices for controlling human organs and treating various diseases.

An on-demand bioresorbable neurostimulator.

Bioresorbable bioelectronics, with their natural degradation properties, hold significant potential to eliminate the need for surgical removal. Despite notable achievements, two major challenges hinder their practical application in medical settings. First, they necessitate sustainable energy solutions with biodegradable components via biosafe powering mechanisms. More importantly, reliability in their function is undermined by unpredictable device lifetimes due to the complex polymer degradation kinetics. Here, we propose an on-demand bioresorbable neurostimulator to address these issues, thus allowing for clinical operations to be manipulated using biosafe ultrasound sources. Our ultrasound-mediated transient mechanism enables (1) electrical stimulation through transcutaneous ultrasound-driven triboelectricity and (2) rapid device elimination using high-intensity ultrasound without adverse health effects. Furthermore, we perform neurophysiological analyses to show that our neurostimulator provides therapeutic benefits for both compression peripheral nerve injury and hereditary peripheral neuropathy. We anticipate that the on-demand bioresorbable neurostimulator will prove useful in the development of medical implants to treat peripheral neuropathy.

Ultrasound-Driven Injectable and Fully Biodegradable Triboelectric Nanogenerators.

Implantable medical devices (IMDs) provide practical approaches to monitor physiological parameters, diagnose diseases, and aid treatment. However, device installation, maintenance, and long-term implantation increase the risk of infection with conventional IMDs. Therefore, medical devices with biocompatibility, controllability, and miniaturization are highly demandable. An ultrasound-driven, biodegradable, and injectable triboelectric nanogenerator (I-TENG) is demonstrated to reduce the risks of implant-related injuries and infections. The injection can be given by subcutaneous injection with a needle to minimize the implantation incision. The stable output of I-TENG is driven by ultrasound (20 kHz, 1 W cm-2 ), with a voltage of 356.8 mV and current of 1.02 µA during in vivo studies and an electric field of about 0.92 V mm-1 during ex vivo experiments. The cell scratch and proliferation assays showed that the delivered electric field effectively increased cell migration and proliferation, indicating a significant potential to accelerate healing with electricity.

Ultrasound-Driven On-Demand Transient Triboelectric Nanogenerator for Subcutaneous Antibacterial Activity.

To prevent surgical site infection (SSI), which significantly increases the rate morbidity and mortality, eliminating microorganisms is prominent. Antimicrobial resistance is identified as a global health challenge. This work proposes a new strategy to eliminate microorganisms of deep tissue through electrical stimulation with an ultrasound (US)-driven implantable, biodegradable, and vibrant triboelectric nanogenerator (IBV-TENG). After a programmed lifetime, the IBV-TENG can be eliminated by provoking the on-demand device dissolution by controlling US intensity with no surgical removal of the device from the body. A voltage of ≈4 V and current of ≈22 µA generated from IBV-TENG under ultrasound in vitro, confirming inactivating ≈100% of Staphylococcus aureus and ≈99% of Escherichia coli. Furthermore, ex vivo results show that IBV-TENG implanted under porcine tissue successfully inactivates bacteria. This antibacterial technology is expected to be a countermeasure strategy against SSIs, increasing life expectancy and healthcare quality by preventing microorganisms of deep tissue.

An Ultrasound-Driven Bioadhesive Triboelectric Nanogenerator for Instant Wound Sealing and Electrically Accelerated Healing in Emergencies.

A bioadhesive triboelectric nanogenerator (BA-TENG), as a first-aid rescue for instant and robust wound sealing and ultrasound-driven accelerated wound healing, is designed. This BA-TENG is fabricated with biocompatible materials, and integrates a flexible TENG as the top layer and bioadhesive as the bottom layer, resulting in effective electricity supply and strong sutureless sealing capability on wet tissues. When driven by ultrasound, the BA-TENG can produce a stable voltage of 1.50 V and current of 24.20 µA underwater. The ex vivo porcine colon organ models show that the BA-TENG seals defects instantly (≈5 s) with high interfacial toughness (≈150 J m-2 ), while the rat bleeding liver incision model confirms that the BA-TENG performs rapid wound closure and hemostasis, reducing the blood loss by about 82%. When applied in living rats, the BA-TENG not only seals skin injuries immediately but also produces a strong electric field (E-field) of about 0.86 kV m-1 stimulated by ultrasound to accelerate skin wound healing significantly. The in vitro studies confirm that these effects are attributed to the E-field-accelerated cell migration and proliferation. In addition, these TENG adhesives can be applied to not only wound treatment, nerve stimulation and regeneration, and charging batteries in implanted devices.

Videoscope-assisted transaortic myectomy in patients with hypertrophic cardiomyopathy with complex left ventricular anatomy.

BACKGROUND: The transaortic approach is the most common method of septal myectomy. However, difficulties arise due to a limited view of the surgical field. Here, we report our experience with videoscope-assisted transaortic myectomy. METHODS: We reviewed myectomy operations that were performed between July 2015 and June 2019 at Chung-Ang University Hospital, Seoul, South Korea. Patients who previously had cardiac surgery, alcohol septal ablation, or concomitant disease which required combined surgery, were excluded. Among the 21 patients included, 10 patients underwent videoscope-assisted transaortic myectomy (VA group), and 11 patients underwent myectomy in a conventional manner (CO group). The preoperative data, echocardiographic images, operative records, and postoperative outcomes of these patients were reviewed. RESULTS: There were no differences in baseline characteristics between groups VA and CO. The main indications for videoscope-assisted transaortic myectomy in group VA were midventricular septal muscle resection (70%), abnormal papillary muscle resection (40%), and abnormal chordal connection resection (30%). Eight (80%) patients had multiple indications for videoscope-assisted transaortic myectomy. There was no surgical mortality in either group. Postoperative patients showed less than moderate mitral regurgitation and a New York Heart Association class either III or IV. There were no differences in hospital days (9.5 vs. 12.0 days; p = .383), nor postoperative pressure gradient (14 vs. 15 mmHg; p > .99). CONCLUSIONS: Videoscope-assisted transaortic myectomy is an effective surgical technique in selective hypertrophic cardiomyopathy patients with complex intraventricular anatomy, diffuse hypertrophy, and midventricular obstruction.

Omega-3 Polyunsaturated Fatty Acids Prevent Toxoplasma gondii Infection by Inducing Autophagy via AMPK Activation.

Omega-3 polyunsaturated fatty acids (ω3-PUFAs) have potential protective activity in a variety of infectious diseases, but their actions and underlying mechanisms in Toxoplasma gondii infection remain poorly understood. Here, we report that docosahexaenoic acid (DHA) robustly induced autophagy in murine bone marrow-derived macrophages (BMDMs). Treatment of T. gondii-infected macrophages with DHA resulted in colocalization of Toxoplasma parasitophorous vacuoles with autophagosomes and reduced intracellular survival of T. gondii. The autophagic and anti-Toxoplasma effects induced by DHA were mediated by AMP-activated protein kinase (AMPK) signaling. Importantly, BMDMs isolated from Fat-1 transgenic mice, a well-known animal model capable of synthesizing ω3-PUFAs from ω6-PUFAs, showed increased activation of autophagy and AMPK, leading to reduced intracellular survival of T. gondii when compared with wild-type BMDMs. Moreover, Fat-1 transgenic mice exhibited lower cyst burden in the brain following infection with the avirulent strain ME49 than wild-type mice. Collectively, our results revealed mechanisms by which endogenous ω3-PUFAs and DHA control T. gondii infection and suggest that ω3-PUFAs might serve as therapeutic candidate to prevent toxoplasmosis and infection with other intracellular protozoan parasites.

Protective effects of a traditional herbal extract from Stellaria dichotoma var. lanceolata against Mycobacterium abscessus infections.

Stellaria dichotoma var. lanceolata (SdLv), a member of the Caryophyllaceae, is a traditional herbal medicine that has been used to treat fever, night sweats, and malaria in East Asia. Inflammation plays an essential role in both host defense and pathogenesis during infection by diverse intracellular pathogens. Herein, we showed that an herbal extract from SdLv effectively attenuated inflammatory responses from infection of Mycobacterium abscessus (Mab), but not Toxoplasma gondii (T. gondii). In primary murine macrophages, Mab infection resulted in the rapid activation of nuclear factor (NF)-κB and mitogen-activated protein kinase (MAPK), as well as in the generation of proinflammatory cytokines, such as tumor necrosis factor α and interleukin-6, which were all significantly inhibited by pretreatment with SdLv. However, herbal extracts from Bupleurum chinense DC. (Buch) or Bupleurum falcatum L. (Bufa) did not affect M. abs-induced activation of proinflammatory responses. Importantly, we demonstrated that generation of intracellular reactive oxygen species, which are important signaling intermediaries in the activation of NF-κB and the MAPK signaling pathway, was rapidly increased in Mab-infected macrophages, and this was effectively suppressed by pretreatment with SdLv, but not Buch and Bufa. We further found that the treatment of Buch and Bufa, but not SdLv, led to the activation of NF-κB and the MAPK signaling pathway and the generation of intracellular reactive oxygen species. Moreover, oral administration of SdLv significantly reduced lethality in Mab-infected mice. Collectively, these results suggest the possible use of SdLv as an effective treatment for Mab infection.

NADPH oxidase 4 is required for the generation of macrophage migration inhibitory factor and host defense against Toxoplasma gondii infection.

Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases (Nox) are an important family of catalytic enzymes that generate reactive oxygen species (ROS), which mediate the regulation of diverse cellular functions. Although phagocyte Nox2/gp91phox is closely associated with the activation of host innate immune responses, the roles of Nox family protein during Toxoplasma gondii (T. gondii) infection have not been fully investigated. Here, we found that T. gondii-mediated ROS production was required for the upregulation of macrophage migration inhibitory factor (MIF) mRNA and protein levels via activation of mitogen-activated protein kinase and nuclear factor-κB signaling in macrophages. Interestingly, MIF knockdown led to a significant increase in the survival of intracellular T. gondii in bone marrow-derived macrophages (BMDMs). Moreover, Nox4 deficiency, but not Nox2/gp91phox and the cytosolic subunit p47phox, resulted in enhanced survival of the intracellular T. gondii RH strain and impaired expression of T. gondii-mediated MIF in BMDMs. Additionally, Nox4-deficient mice showed increased susceptibility to virulent RH strain infection and increased cyst burden in brain tissues and low levels of MIF expression following infection with the avirulent ME49 strain. Collectively, our findings indicate that Nox4-mediated ROS generation plays a central role in MIF production and resistance to T. gondii infection.

High-intensity focused ultrasound combined with hysteroscopic resection to treat retained placenta accreta.

We present a case of retained placenta accreta treated by high-intensity focused ultrasound (HIFU) ablation followed by hysteroscopic resection. The patient was diagnosed as submucosal myoma based on ultrasonography in local clinic. Pathologic examination of several pieces of tumor mass from the hysteroscopic procedure revealed necrotic chorionic villi with calcification. HIFU was performed using an ultrasound-guided HIFU tumor therapeutic system. The ultrasound machine had been used for real-time monitoring of the HIFU procedure. After HIFU treatment, no additional vaginal bleeding or complications were observed. A hysteroscopic resection was performed to remove ablated placental tissue 7 days later. No abnormal vaginal bleeding or discharge was seen after the procedure. The patient was stable postoperatively. We proposed HIFU and applied additional hysteroscopic resection for a safe and effective method for treating retained placenta accreta to prevent complications from the remaining placental tissue and to improve fertility options.

STAT3 and ERK Signaling Pathways Are Implicated in the Invasion Activity by Oncostatin M through Induction of Matrix Metalloproteinases 2 and 9.

PURPOSE: Our previous studies have shown that oncostatin M (OSM) promotes trophoblast invasion activity through increased enzyme activity of matrix metalloproteinase (MMP)-2 and -9. We further investigated OSM-induced intracellular signaling mechanisms associated with these events in the immortalized human trophoblast cell line HTR8/SVneo. MATERIALS AND METHODS: We investigated the effects of OSM on RNA and protein expression of MMP-2 and -9 in the first-trimester extravillous trophoblast cell line (HTR8/SVneo) via Western blot. The selective signal transducer and activator of transcription (STAT)3 inhibitor, stattic, STAT3 siRNA, and extracellular signal-regulated kinase (ERK) siRNA were used to investigate STAT3 and ERK activation by OSM. The effects of STAT3 and ERK inhibitors on OSM-induced enzymatic activities of MMP-2 and -9 and invasion activity were further determined via Western blot and gelatin zymography. RESULTS: OSM-induced MMP-2 and -9 protein expression was significantly suppressed by STAT3 inhibition with stattic and STAT3 siRNA silencing, whereas the ERK1/2 inhibitor (U0126) and ERK silencing significantly suppressed OSM-induced MMP-2 protein expression. OSM-induced MMP-2 and MMP-9 enzymatic activities were significantly decreased by stattic pretreatment. The increased invasion activity induced by OSM was significantly suppressed by STAT3 and ERK1/2 inhibition, though to a greater extent by STAT3 inhibition. CONCLUSION: Both STAT3 and ERK signaling pathways are involved in OSM-induced invasion activity of HTR8/SVneo cells. Activation of STAT3 appears to be critical for the OSM-mediated increase in invasiveness of HTR8/SVneo cells.

Comparative analysis of trunk muscle activities in climbing of during upright climbing at different inclination angles.

[Purpose] This study was performed to provide evidence for the therapeutic exercise approach through a compative analysis of muscle activities according to climbing wall inclination. [Subjects and Methods] Twentyfour healthy adult subjects without climbing experience performed static exercises at a therapeutic climbing at with various inclination angles (0°, 10°, 20°), and the activities of the trunk muscles (rectus abdominis, obliquus externus abdominis, obliquus internus abdominis, erector spinae) were measured using surface electromyography (EMG) for 7 seconds. [Results] Significant differences were found between the inclination angles of 10° and 0°, as well as 20° in the rectus abdominis, obliquus internus abdominis, right obliquus externus abdominis, and right erector spinae. [Conclusion] Based on measurements of trunk muscle activity in a static climbing standing position at different angles, significant changes in muscle activity appear to be induced at 10 degrees. Therefore, the results appear to provide clinically relevant evidence.

The effect of fibroblast growth factor on distinct differentiation potential of cord blood-derived unrestricted somatic stem cells and Wharton's jelly-derived mesenchymal stem/stromal cells.

BACKGROUND AIMS: Perinatal tissues are considered an attractive source of mesenchymal stem/stromal cells (MSCs) and have unique characteristics depending on their origin. In this study, we compared the basic characteristics of unrestricted somatic stem cells isolated from cord blood (CB-USSCs) and MSCs isolated from Wharton's jelly of umbilical cords (WJ-MSCs). We also evaluated the effect of basic fibroblast growth factor (bFGF) supplementation on the growth and differentiation of these cells. METHODS: CB-USSCs and WJ-MSCs were isolated from the same individual (n = 6), and their morphology, cell surface antigens, proliferation, expression of stemness markers and adipogenic, osteogenic and chondrogenic differentiation potentials were evaluated. Their morphology, proliferation and differentiation potentials were then also compared in the presence of bFGF supplementation (10 ng/mL). RESULTS: Overall, CB-USSCs expressed DLK-1 and negative for all the HOX gene markers. The expression of cell surface antigen CD90, growth capacity and adipogenic differential potential of CB-USSCs were lower than those of WJ-MSCs. WJ-MSCs showed higher growth capacity, but the expression of CD73 and CD105 and their osteogenic differentiation potential were lower than those of CB-USSCs. The spindle morphology of both CB-USSCs and WJ-MSCs and the growth and adipogenic differentiation of CB-USSCs were improved by bFGF supplementation. However, the bFGF supplement did not have any positive effect on the tri-lineage differentiation potentials of WJ-MSCs. CONCLUSIONS: CB-USSCs and WJ-MSCs each had distinct characteristics including different growth capacity, distinguishable cell surface markers and distinct adipogenic and osteogenic potentials. bFGF supplementation improved the growth capacity and adipogenic differentiation of CB-USSCs.

Characterization of two alkyl hydroperoxide reductase C homologs alkyl hydroperoxide reductase C_H1 and alkyl hydroperoxide reductase C_H2 in Bacillus subtilis.

AIM: To identify alkyl hydroperoxide reductase subunit C (AhpC) homologs in Bacillus subtilis (B. subtilis) and to characterize their structural and biochemical properties. AhpC is responsible for the detoxification of reactive oxygen species in bacteria. METHODS: Two AhpC homologs (AhpC_H1 and AhpC_H2) were identified by searching the B. subtilis database; these were then cloned and expressed in Escherichia coli. AhpC mutants carrying substitutions of catalytically important Cys residues (C37S, C47S, C166S, C37/47S, C37/166S, C47/166S, and C37/47/166S for AhpC_H1; C52S, C169S, and C52/169S for AhpC_H2) were obtained by site-directed mutagenesis and purified, and their structure-function relationship was analyzed. The B. subtilis ahpC genes were disrupted by the short flanking homology method, and the phenotypes of the resulting AhpC-deficient bacteria were examined. RESULTS: Comparative characterization of AhpC homologs indicates that AhpC_H1 contains an extra C37, which forms a disulfide bond with the peroxidatic C47, and behaves like an atypical 2-Cys AhpC, while AhpC_H2 functions like a typical 2-Cys AhpC. Tryptic digestion analysis demonstrated the presence of intramolecular Cys37-Cys47 linkage, which could be reduced by thioredoxin, resulting in the association of the dimer into higher-molecular-mass complexes. Peroxidase activity analysis of Cys→Ser mutants indicated that three Cys residues were involved in the catalysis. AhpC_H1 was resistant to inactivation by peroxide substrates, but had lower activity at physiological H2O2 concentrations compared to AhpC_H2, suggesting that in B. subtilis, the enzymes may be physiologically functional at different substrate concentrations. The exposure to organic peroxides induced AhpC_H1 expression, while AhpC_H1-deficient mutants exhibited growth retardation in the stationary phase, suggesting the role of AhpC_H1 as an antioxidant scavenger of lipid hydroperoxides and a stress-response factor in B. subtilis. CONCLUSION: AhpC_H1, a novel atypical 2-Cys AhpC, is functionally distinct from AhpC_H2, a typical 2-Cys AhpC.

Ultrasound-guided high-intensity focused ultrasound treatment for uterine fibroid & adenomyosis: A single center experience from the Republic of Korea.

OBJECTIVES: This study aimed to assess the therapeutic outcomes of patients with uterine fibroid or adenomyosis treated by ultrasound-guided high-intensity focused ultrasound (USgHIFU) ablation at Incheon Christian Hospital, Korea. METHODS: This study included 618 patients, of which 272 suffered from uterine fibroid and 346 suffered from adenomyosis. Treatment was administrated using the Model Haifu JC Focused Ultrasound Tumor Therapeutic System (Chongqing Haifu Technology, Chongqing, China) under real-time ultrasound guidance. A follow-up was conducted on volume change as well as on symptom improvement using the Symptom Severity Score (SSS) and Uterine Fibroid Symptom and Quality of Life (UFS-QOL) after treatment. RESULT: The uterine fibroid volume reduction rates (%) were 58.08%, 66.18%, and 77.59% at 3, 6, and 12 months after treatment, respectively. The SSS reduction rates (%) were 55.58%, 52.76%, and 50.39% by 3, 6, and 12 months, respectively. The UFS-QOL score increasing rates (%) were 42.66%, 43.50%, and 43.45% by 3, 6, and 12 months, respectively. The uterine volume reduction rates (%) for adenomyosis were 43.99%, 47.01%, and 53.98% by 3, 6, and 12 months, respectively. The SSS reduction rates (%) for adenomyosis were 55.61%, 52.38%, and 57.98% by 3, 6, and 12 months, respectively. The UFS-QOL score increasing rates (%) for adenomyosis UFS-QOL score were 80.06%, 69.39%, and 85.07% by 3, 6, and 12 months, respectively. CONCLUSION: We conclude that USgHIFU treatment for uterine fibroid and adenomyosis is an effective non-invasive therapy via the assessment of fibroid volume reduction, symptom improvement, UFS-QOL score increase, and acceptable level of side effects. Although preliminary experience of HIFU is encouraging, well-designed prospective trials and more clinical experiences are needed to ascertain the efficacy and safety of this new treatment.

Thioredoxin 1 as a serum marker for ovarian cancer and its use in combination with CA125 for improving the sensitivity of ovarian cancer diagnoses.

The serum levels of Trx1 in patients with ovarian cancer were significantly higher than those in normal persons and patients with non-cancer inflammatory diseases. The level of Trx1 increased with the Figo stage. Ovarian cancer patients who were determined to be negative for CA125, were observed to have serum Trx1 levels as high as those of CA125-positive patients. In addition, patients with non-cancer inflammatory diseases had lower plasma Trx1 1 levels than did controls, showing that Trx1 allows clear distinctions between ovarian cancer and these non-cancer diseases. Combinational analysis of CA125 with Trx1 for the detection of ovarian cancer suggests that the diagnostic capacity of CA125 alone for the early detection of ovarian cancer, especially regarding sensitivity, is significantly improved by its combination with Trx1. Taken together, we conclude that serum Trx1 is useful for the early diagnosis of ovarian cancer.

Thioredoxin 1 as a serum marker for breast cancer and its use in combination with CEA or CA15-3 for improving the sensitivity of breast cancer diagnoses.

BACKGROUND: The human cytosolic thioredoxin (Trx) contains a redox-active dithiol moiety in its conserved active-site sequence. Activation by a wide variety of stimuli leads to secretion of this cytoplasmic protein. Function of Trx1 has been implicated in regulating cell proliferation, differentiation, and apoptosis. The aim of this study was to assess the clinical significance of serum Trx1 level in patients with breast carcinoma. RESULTS: To clarify whether serum levels of Trx1 could be a serum marker for breast carcinoma, we measured the serum levels of Trx1 in patients with various carcinomas (breast, lung, colorectal, and kidney cancers) using an ELISA, and investigated its associations with the tumour grading from I to III. At the cut-off point 33.1725 ng/ml on the receiver operating characteristic curve (ROC) Trx1 could well discriminate breast carcinoma from normal controls with a sensitivity of 89.8%, specificity 78.0%, and area under the ROC (AUC) 0.901 ± 0.0252. The serum level was well correlated with the progress of the breast carcinoma. We also investigated the diagnostic capacity of CEA and CA15-3 for the early detection of metastatic breast cancer comparing that of Trx1. In contrast to the serum CEA and CA15-3 tumour markers, the serum Trx1 levels of the early cancer (grade I) patients were significantly higher than those of normal control subjects, showing a high diagnostic sensitivity and selectivity (89.4% sensitivity, and 72.0% specificity). The serum levels of Trx1 in various patients with lung, colorectal, and kidney carcinomas indicate that the level of Trx1 is significantly higher than those of other cancer patients. Combinational analysis of CEA or CA15-3 with Trx1 for the detection of breast cancer suggest that the diagnostic capacity of CEA or CA15-3 alone for the early detection of breast cancer, especially regarding sensitivity, is significantly improved by its combination with Trx1. CONCLUSIONS: Taken together, we conclude that serum Trx1 is useful for the early diagnosis of breast cancer or the early prediction prognosis of breast cancer, and therefore has a valuable use as a diagnostic marker and companion marker to CEA and CA15-3 for breast cancer.