The lectin‐like domain of thrombomodulin is a drug candidate for both prophylaxis and treatment of liver ischemia and reperfusion injury in mice

Ischemia and reperfusion injury (IRI) can occur in any tissue or organ. With respect to liver transplantation, the liver grafts from donors by definition experience transient ischemia and subsequent blood reflow. IRI is a problem not only in organ transplantation but also in cases of thrombosis or circulatory disorders such as mesenteric ischemia, myocardial, or cerebral infarction. We have reported that recombinant human soluble thrombomodulin (rTM), which is currently used in Japan to treat disseminated intravascular coagulation (DIC), has a protective effect and suppresses liver IRI in mice. However, rTM may not be fully safe to use in humans because of its inherent anticoagulant activity. In the present study, we used a mouse liver IRI model to explore the possibility that the isolated lectin-like domain of rTM (rTMD1), which has no anticoagulant activity, could be effective as a therapeutic modality for IRI. Our results indicated that rTMD1 could suppress ischemia and reperfusion-induced liver damage in a dose-dependent manner without concern of associated hemorrhage. Surprisingly, rTMD1 suppressed the liver damage even after IR insult had occurred. Taken together, we conclude that rTMD1 may be a candidate drug for prevention of and therapy for human liver IRI without the possible risk of hemorrhage

Effect of Alumina Nanoparticles on Lentil Seed Germination Using Biospeckle Optical Coherence Tomography

The industrial use of nanoparticles is rapidly increasing in agricultural products, and it causes numerous effects on plant growth and seed germination. There are limited studies about the uptake, accumulation, and effect of nanoparticles on plant growth. Moreover, there are no studies that have been able to measure the biological activity of seeds’ interiors under nanoparticle treatment prior to germination. Hence, in this study, the possible size-defendant effect of alumina nanoparticles on lentil (Lens culinaris) seed germination was monitored using biospeckle Optical Coherence Tomography (bOCT) at an early stage before germination. bOCT is a non-contact, non-destructive, and non-invasive image modality developed by researchers to visualize internal biological activities in vivo. Previous studies by researchers using the technique have demonstrated its potential to observe the effect of different stimuli on seed germination at an early stage before germination occurs. In the present study, the possible size-defendant effect of 200 nm and 2000 nm alumina nanoparticles (AlNPs) on lentil seed germination was examined at a concentration of 100 mg/L. The results imply that the AlNPs could enhance lentil seed germination and seedling growth compared to control treatments, and the effect is more significant as the particle size decreases. This is believed to be due to the enhancement of energy metabolism under exposure to AlNPs

CD4+ T Cell NRF2 Signaling Improves Liver Transplantation Outcomes by Modulating T Cell Activation and Differentiation.

Aims: Innate and adaptive immune responses regulate hepatic ischemia-reperfusion injury (IRI) in orthotopic liver transplantation (OLT). While the mechanism of how nuclear factor erythroid 2-related factor 2 (NRF2) plays a role in liver IRI has been studied, the contribution of T cell-specific NRF2 in OLT remains unknown. In the current translational study, we investigated whether and how CD4+ T cell-specific NRF2 signaling affects liver transplant outcomes in mice and humans. Results: In the experimental arm, cold-stored (4°C/18 h) wild-type (WT) mouse livers transplanted to NRF2-deficient (NRF2-knockout [NRF2-KO]) recipients experienced greater hepatocellular damage than those in Nrf2-proficient (WT) counterparts, evidenced by Suzukis histological scores, frequency of TdT-mediated dUTP nick end labeling (TUNEL)+ cells, and elevated serum aspartate aminotransferase/alanine aminotransferase (AST/ALT) levels. In vitro studies showed that NRF2 signaling suppressed CD4+ T cell differentiation to a proinflammatory phenotype (Th1, Th17) while promoting the regulatory (Foxp3+) T cell lineage. Furthermore, OLT injury deteriorated in immune-compromised RAG2-KO test recipients repopulated with CD4+ T cells from NRF2-KO compared with WT donor mice. In the clinical arm of 45 human liver transplant patients, the perioperative increase of NRF2 expression in donor livers negatively regulated innate and adaptive immune activation, resulting in reduced hepatocellular injury in NRF2-proficient OLT. Innovation and Conclusion: CD4+ T cell population expressing NRF2 attenuated ischemia and reperfusion (IR)-triggered hepatocellular damage in a clinically relevant mouse model of extended donor liver cold storage, followed by OLT, whereas the perioperative increase of NRF2 expression reduced hepatic injury in human liver transplant recipients. Thus, CD4+ T cell NRF2 may be a novel cytoprotective sentinel against IR stress in OLT recipients. Antioxid. Redox Signal. 38, 670-683

The Plastic Within: Microplastics Invading Human Organs and Bodily Fluids Systems

Microplastics (MPs), small plastic particles resulting from the degradation of larger plastic items and from primary sources such as textiles, engineered plastic pellets, etc., have become a ubiquitous environmental pollutant. As their prevalence in the natural environment grows, concerns about their potential impacts on human health have escalated. This review discusses current research findings on the presence of MPs in organs such as the liver, blood, heart, placenta, breast milk, sputum, semen, testis, and urine, while also exploring plausible mechanisms of translocation. Furthermore, the review emphasizes the importance of understanding the potential toxicological effects of MPs on various physiological processes within these organs and their broader implications for human health. This review also examines the pathways through which MPs can enter and accumulate in human organs and bodily fluids, shedding light on the intricate routes of exposure and potential health implications. It is worth noting that the invasive medical procedures may permit direct access of MPs to the bloodstream and tissues, serving as a potential contamination source. However, it is evident that a comprehensive understanding of MPs’ invasion into human organs is vital for effective mitigation strategies and the preservation of both human health and the environment

A Real-Time, Non-Invasive Technique for Visualizing the Effects of Acid Mine Drainage (AMD) on Soybean

Acid mine drainage is a serious environmental problem faced by the mining industry globally, causing the contamination of numerous agricultural lands and crops. Against this background, this study aims to investigate the effects of AMD on soybean, one of the major crops. To monitor the effects of AMD on soybean quickly and non-destructively, we have proposed a technique called biospeckle optical coherence tomography (bOCT). Soaked soybean seeds were monitored by bOCT, once after 6 h and again after germination, i.e., 48 h, and the results were compared with conventional parameters such as enzyme activity, iron uptake, and seedling length. It was found that bOCT could detect the effects due to the AMD after just 6 h with a decrease in a parameter called bisopeckle contrast that reflects the internal activity of the seeds. On the other hand, the conventional parameters required a week for the effects to appear, and the results from bOCT after six hours were consistent with those obtained by conventional measures. Because of the non-invasive nature of bOCT, requiring only tens of seconds of measurement with an intact, it has not only the potential to screen but could also constantly monitor long-term changes, thus possibly contributing to the study of the effects of AMD on crops

A Real-Time, Non-Invasive Technique for Visualizing the Effects of Acid Mine Drainage (AMD) on Soybean

Acid mine drainage is a serious environmental problem faced by the mining industry globally, causing the contamination of numerous agricultural lands and crops. Against this background, this study aims to investigate the effects of AMD on soybean, one of the major crops. To monitor the effects of AMD on soybean quickly and non-destructively, we have proposed a technique called biospeckle optical coherence tomography (bOCT). Soaked soybean seeds were monitored by bOCT, once after 6 h and again after germination, i.e., 48 h, and the results were compared with conventional parameters such as enzyme activity, iron uptake, and seedling length. It was found that bOCT could detect the effects due to the AMD after just 6 h with a decrease in a parameter called bisopeckle contrast that reflects the internal activity of the seeds. On the other hand, the conventional parameters required a week for the effects to appear, and the results from bOCT after six hours were consistent with those obtained by conventional measures. Because of the non-invasive nature of bOCT, requiring only tens of seconds of measurement with an intact, it has not only the potential to screen but could also constantly monitor long-term changes, thus possibly contributing to the study of the effects of AMD on crops

Microbiota in organ transplantation: An immunological and therapeutic conundrum?

The gastrointestinal (GI) tract microbiota is an environmental factor that regulates host immunity in allo-transplantation (allo-Tx). It is required for the development of resistance against pathogens and the stabilization of mucosa-associated lymphoid tissue. The gut-microbiota axis may also precipitate allograft rejection by producing metabolites that activate host cell-mediated and humoral immunity. Here, we discuss new insights into microbial immunomodulation, highlighting ongoing attempts to affect commensal colonization in an attempt to ameliorate allograft rejection cascade. Recent progress on the use of antibiotics to modulate GI microbiota diversity and innate-adaptive immune interface are discussed. Our focus on the microbiota's influence of endoplasmic reticulum (ER) stress and autophagy signaling through hepatic EP4/CHOP/LC3B platforms reveals a novel molecular pathway and potential biomarkers determining the progression of allo-Tx damage. Understanding and harnessing the potential of microbiome/bacteriophage therapies may offer safe and effective means for personalized treatment to reduce risks of infections and immunosuppression in allo-Tx

Biospeckle Optical Coherence Tomography (bOCT) in the Speedy Assessment of the Responses of the Seeds of <i>Raphanus sativus</i> L. (Kaiware Daikon) to Acid Mine Drainage (AMD)

The extraction of mineral resources from mines plays a vital role in global socio-economic development. However, acid mine drainage (AMD) has been one of the major pollutants, and a vast area of the agricultural fields has been polluted. Therefore, techniques for monitoring the response of plants to AMD that arise during mineral extraction are necessary. In addition, such a technique becomes especially valuable to understand how the plants could play a role in the phytoremediation of AMD. We propose the use of biospeckle Optical Coherence Tomography (bOCT) to investigate the response of Kaiware daikon seeds under the exposure to simulated AMD at two different concentrations of 40 mL/L and 80 mL/L. OCT images of the Kaiware daikon seed were obtained at a speed of 10 frames per second (1 frame: 512 × 2048 pixels) for a few tens of seconds. For each pixel of the OCT structural images, the contrast across the temporal axis was calculated to give biospeckle contrast OCT images (bOCT images). It was found that bOCT images clearly distinguished the changes due to 40 mL/L and 80 mL/L of AMD treatments from the control within a short time of around an hour, compared to the conventional OCT images that failed to show any changes. This variation was found to be statistically significant and could reflect the internal activity of the seeds. The proposed bOCT method could be a rapid, non-invasive technique for screening suitable plants in AMD phytoremediation applications

Lower Extremity Power Training Improves Healthy Old Adults’ Gait Biomechanics

Purpose: Age-related slowing of gait speed predicts many clinical conditions in later life. We examined the kinematic and kinetic mechanisms of how lower extremity power training increases healthy old adults’ gait speed. Methods: We randomly allocated old adults to a training (age 74.3 y, 9 males, 6 females) and a control group (age 73.6 y, 3 males, 4 females) and compared the biomechanics of habitual and fast gait before and after 16 sessions (8 weeks) of lower extremity power training. Results: Training increased maximal leg press load by ∼40% (P \u3c 0.05) and maximal voluntary force in five groups of leg muscles by ∼32% (P \u3c 0.05) in the training group. Training vs. control tended to increase habitual (10.8 vs. 7.6%) and fast gait speed (17.6 vs. 9.0%; all P \u3c 0.05) more. In the training group only, these increases in gait speed correlated with increases in stride length (habitual: r2 = 0.84, fast: r2 = 0.89). Training made old adults’ gait more erect: hip and knee extension increased in the stance phase of gait. Training increased ankle joint positive work by 3.3 J (control: −0.4 J, Group by Time interaction: P \u3c 0.05), which correlated r2 = 0.58 and r2 = 0.67 with increases in habitual and fast gait speed without changes in hip and knee joint powers. Conclusion: Increases in leg muscle power increased healthy old adults’ gait speed through correlated increases in stride length and ankle plantarflexor work generation