Uncoupling protein 3 attenuates generation of reactive oxygen species by interacting with thioredoxin 2 in the mitochondrial intermembrane space

Katsuya Hirasaka1*, Edward M Mills2, Shohei Kohno1, Tomoki Abe1, Chika Ikeda1, Tasuku Maeda1, Shigetada Kondo1, Ayako Maita1, Yuushi Okumura1 and Takeshi Nikawa1 Author Affiliations 1 Department of Nutritional Physiology, Institute of Health Biosciences, University of Tokushima, Tokushima, 770-8503, Japan 2 Division of Pharmacology/Toxicology, University of Texas at Austin, Austin, TX 78712, USAPoster presentation Uncoupling protein 3 (UCP3) is primarily expressed in the inner membrane of skeletal muscle mitochondria. It has been proposed that UCP3 reduces production of reactive oxygen species (ROS) and oxidative damage. However, the mechanisms by which UCP3 attenuates ROS production are not well understood. Here we report that UCP3 interacts with the non-processed form of thioredoxin 2 (Trx2), a redox protein that is localized in mitochondria, but not processed Trx2, which is involved in cellular responses to ROS. The hydrophilic sequences within the N-terminal tail of UCP3, which faces the intermembrane space, are necessary for binding to Trx2. In addition, Trx2 directly associated with UCP3 through a mitochondrial targeting signaling sequence, was processed in the intermembrane space, and thereby allowing redox reactions. A bimolecular fluorescence complementation analysis demonstrated that the interaction of these proteins occurs in the mitochondrial intermembrane space. Furthermore, increased UCP3 expression significantly attenuated ROS production in isolated mitochondrial without effects on membrane potential, however this effect is lost by Trx2 knock down. These results suggest that UCP3 binds to Trx2 in the mitochondrial intermembrane space and attenuates ROS production.Pharmac

Is it practical to determine the therapeutic strategy for breast cancer by evaluating pathological findings in core needle biopsy specimens?

Background; Core needle biopsy (CNB) specimens have been widely used not only for the diagnosis of breast cancer, but also for assessing biomarkers, including lymphovascular invasion (ly and v), nuclear grading, the estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER-2) and Ki-67. We herein compared the pathological biomarkers of ER+/HER2- invasive breast cancers in CNB with those in the subsequent surgical specimens.　Methods; Patients with ER+/HER2- invasive breast cancer who presented to our department from August 2011 to July 2013 who had CNB and subsequent surgery were included. Lymphovascular invasion (ly, v) and nuclear grading were determined by hematoxylin and eosin staining, and the ER, PgR, HER-2, and Ki-67 status were evaluated by immunohistochemistry.　Results; The concordance rates between CNB and surgical specimens for the ly, v, nuclear grading, ER and PgR were 2.4%, 2.9%, 63.0%, 96.4% and 82.1%, respectively. Lymphovascular invasion and nuclear grading tended to be underestimated with CNB in discordant cases. The Ki-67 labeling index in CNB specimens was strongly correlated with that in surgical specimens (correlation coefficient 0.75, p<0.0001). Consequently, there was a reasonable level of agreement between CNB and surgical specimens for surrogate subtyping (82.1%).　Conclusions; CNB provided reliable information on the expression of hormone receptors, Ki-67 in ER+/HER2- invasive breast cancers. However, because of the substantial discordance between CNB and surgical specimens, the status of lymphovascular invasion and nuclear grading should not be concluded based on CNB specimens

Idobata-Nagaya: a community housing solution for socially isolated older adults following the great East Japan earthquake

IntroductionFollowing the Great East Japan Earthquake, the living environment of socially isolated older adults has become a pressing concern. In response, Nagaya, a collective housing program, was established in Soma City, Fukushima, Japan to address social isolation among older adults and support their long-term health. This study aimed to identify characteristics of individuals in Nagaya and examine the sustainability of this initiative.MethodsWe conducted a retrospective analysis of residents who were relocated to Nagaya, emphasizing their characteristics, the continuity of their stay in Nagaya, and their care certification levels, using data up to December 31, 2022. We employed Kaplan–Meier curves to analyze the duration for which residents continued to reside in Nagaya and the time leading up to the requiring care-level certification.ResultsOf 65 people who moved to Nagaya after the disaster, 30 people (46.2%) continued to live there, 21 (32.3%) died during their stay, and 14 (21.5%) moved out. The overall duration of occupancy averaged 6.39 years (SD 3.83 years). The proportion of requiring care-level certification occurrences per person-year was 0.0577 for those without care certification and 0.3358 for those with requiring support level at the time of moving in.ConclusionIn summary, Nagaya-style communal housing may offer suitable living environments for older adults with diverse needs during disasters and serve as a valuable tool for developing public policies in aging societies

Diminished neutralizing activity against the XBB1.5 strain in 55.9% of individuals post 6 months COVID-19 mRNA booster vaccination: insights from a pseudovirus assay on 1,353 participants in the Fukushima vaccination community survey, Japan

This study investigates the neutralizing activity against the XBB1.5 variant and the ancestral strain in a population post-bivalent vaccination using a pseudo virus assay validated with authentic virus assay. While bivalent booster vaccination and past infections enhanced neutralization against the XBB 1.5 strain, individuals with comorbidities showed reduced responses. The study suggests the need for continuous vaccine updates to address emerging SARS-CoV-2 variants and highlights the importance of monitoring real-world immune responses

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance.

Investment in severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing in Africa over the past year has led to a major increase in the number of sequences that have been generated and used to track the pandemic on the continent, a number that now exceeds 100,000 genomes. Our results show an increase in the number of African countries that are able to sequence domestically and highlight that local sequencing enables faster turnaround times and more-regular routine surveillance. Despite limitations of low testing proportions, findings from this genomic surveillance study underscore the heterogeneous nature of the pandemic and illuminate the distinct dispersal dynamics of variants of concern-particularly Alpha, Beta, Delta, and Omicron-on the continent. Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve while the continent faces many emerging and reemerging infectious disease threats. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

A year of genomic surveillance reveals how the SARS-CoV-2 pandemic unfolded in Africa.

The progression of the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) pandemic in Africa has so far been heterogeneous, and the full impact is not yet well understood. In this study, we describe the genomic epidemiology using a dataset of 8746 genomes from 33 African countries and two overseas territories. We show that the epidemics in most countries were initiated by importations predominantly from Europe, which diminished after the early introduction of international travel restrictions. As the pandemic progressed, ongoing transmission in many countries and increasing mobility led to the emergence and spread within the continent of many variants of concern and interest, such as B.1.351, B.1.525, A.23.1, and C.1.1. Although distorted by low sampling numbers and blind spots, the findings highlight that Africa must not be left behind in the global pandemic response, otherwise it could become a source for new variants

The evolving SARS-CoV-2 epidemic in Africa: Insights from rapidly expanding genomic surveillance

INTRODUCTION Investment in Africa over the past year with regard to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) sequencing has led to a massive increase in the number of sequences, which, to date, exceeds 100,000 sequences generated to track the pandemic on the continent. These sequences have profoundly affected how public health officials in Africa have navigated the COVID-19 pandemic. RATIONALE We demonstrate how the first 100,000 SARS-CoV-2 sequences from Africa have helped monitor the epidemic on the continent, how genomic surveillance expanded over the course of the pandemic, and how we adapted our sequencing methods to deal with an evolving virus. Finally, we also examine how viral lineages have spread across the continent in a phylogeographic framework to gain insights into the underlying temporal and spatial transmission dynamics for several variants of concern (VOCs). RESULTS Our results indicate that the number of countries in Africa that can sequence the virus within their own borders is growing and that this is coupled with a shorter turnaround time from the time of sampling to sequence submission. Ongoing evolution necessitated the continual updating of primer sets, and, as a result, eight primer sets were designed in tandem with viral evolution and used to ensure effective sequencing of the virus. The pandemic unfolded through multiple waves of infection that were each driven by distinct genetic lineages, with B.1-like ancestral strains associated with the first pandemic wave of infections in 2020. Successive waves on the continent were fueled by different VOCs, with Alpha and Beta cocirculating in distinct spatial patterns during the second wave and Delta and Omicron affecting the whole continent during the third and fourth waves, respectively. Phylogeographic reconstruction points toward distinct differences in viral importation and exportation patterns associated with the Alpha, Beta, Delta, and Omicron variants and subvariants, when considering both Africa versus the rest of the world and viral dissemination within the continent. Our epidemiological and phylogenetic inferences therefore underscore the heterogeneous nature of the pandemic on the continent and highlight key insights and challenges, for instance, recognizing the limitations of low testing proportions. We also highlight the early warning capacity that genomic surveillance in Africa has had for the rest of the world with the detection of new lineages and variants, the most recent being the characterization of various Omicron subvariants. CONCLUSION Sustained investment for diagnostics and genomic surveillance in Africa is needed as the virus continues to evolve. This is important not only to help combat SARS-CoV-2 on the continent but also because it can be used as a platform to help address the many emerging and reemerging infectious disease threats in Africa. In particular, capacity building for local sequencing within countries or within the continent should be prioritized because this is generally associated with shorter turnaround times, providing the most benefit to local public health authorities tasked with pandemic response and mitigation and allowing for the fastest reaction to localized outbreaks. These investments are crucial for pandemic preparedness and response and will serve the health of the continent well into the 21st century

Use of FDG PET to Evaluate Hyperbaric Oxygen Therapy for Bisphosphonate-Related Osteonecrosis of the Jaw

An 80-year-old man presented with painful swelling in the mandibular region and fistula with pus discharge that developed after tooth extractions. He had taken oral alendronate sodium hydrate and prednisolone for osteoporosis for five years. The lesion was diagnosed as bisphosphonate-related osteonecrosis of the jaw. FDG-PET revealed a high accumulation of FDG in the right mandibular region. The patient underwent hyperbaric oxygen therapy twenty times. FDG-PET SUVmax drastically decreased from 5.6 to 1.8 after hyper baric oxygen therapy, paralleling the change in clinical symptoms, while other modalities did not show remarkable changes. This is the first study demonstrating the utility of FDG-PET in monitoring hyper baric oxygen therapy for bisphosphonate-related osteonecrosis of the jaw