Alterations in sea urchin (Mesocentrotus nudus) microbiota and their potential contributions to host according to barren severity.

Sea urchins are biotic factors driving the decline of kelp forests in marine ecosystems. However, few studies have analyzed the microbiota of surviving sea urchins in barren regions with scarce diet resources. Here, we analyzed the microbiota in the pharynx and gut of the sea urchin Mesocentrotus nudus located along the coast of an expanding barren region in South Korea. The ecological adaptation of genera in sea urchins was predicted using the neutral assembly model. The pharynx and gut microbiota were different, and microbes in the surrounding habitats dispersed more to the pharynx than to the gut. The gut microbiota in sea urchins is altered by barren severity and plays different roles in host energy metabolism. These findings help to understand the microbiota in sea urchins according to urchin barren and its contribution to the survival of sea urchins in severe barren regions with limited macroalgae.

Phototherapy: A Conventional Approach to Overcome the Barriers in Oncology Therapeutics.

Cancer disease has outgrown a life-threatening disease. Having reference to preceding reports provided by the International Agency for Research on Cancer, an estimated 9.6 million deaths transpired from cancer worldwide in 2018. Similarly, about 18.1 million new cases of cancer are being reported. The rise in conventional treatments akin to surgeries, chemotherapies, and radiotherapies was enormously observed to eradicate cancer tumors. These studies have shown unfavorable side effects in clinical treatments. Drug resistivity and drug cytotoxicities are also major issues to overcome. Considering these, researchers are developing alternative methods that are robust, economical, and safe. The use of light for therapeutic purposes shows a great history in vitiligo treatment. The combination of an effective activating agent and phototherapy could result as the best alternative with a great outcome to minimize adverse effects on healthy tissues. The utilization of light in the deletion of tumors using photothermal agents, and photosensitizers, hence the phototherapies in oncology were discovered and rapidly involved in the advancement of clinical approach. Here, in this article, we tried to highlight the recent trends in phototherapy and reviewed different types of phototherapy methods in cancer treatments and their latest clinical, preclinical, and in vivo studies.

Flow pattern-dependent mitochondrial dynamics regulates the metabolic profile and inflammatory state of endothelial cells.

Endothelial mitochondria play a pivotal role in maintaining endothelial cell (EC) homeostasis through constantly altering their size, shape, and intracellular localization. Studies show that the disruption of the basal mitochondrial network in EC, forming excess fragmented mitochondria, implicates cardiovascular disease. However, cellular consequences underlying the morphological changes in the endothelial mitochondria under distinctively different, but physiologically occurring, flow patterns (i.e., unidirectional flow [UF] versus disturbed flow [DF]) are largely unknown. The purpose of this study was to investigate the effect of different flow patterns on mitochondrial morphology and its implications in EC phenotypes. We show that mitochondrial fragmentation is increased at DF-exposed vessel regions, where elongated mitochondria are predominant in the endothelium of UF-exposed regions. DF increased dynamin-related protein 1 (Drp1), mitochondrial reactive oxygen species (mtROS), hypoxia-inducible factor 1, glycolysis, and EC activation. Inhibition of Drp1 significantly attenuated these phenotypes. Carotid artery ligation and microfluidics experiments further validate that the significant induction of mitochondrial fragmentation was associated with EC activation in a Drp1-dependent manner. Contrarily, UF in vitro or voluntary exercise in vivo significantly decreased mitochondrial fragmentation and enhanced fatty acid uptake and OXPHOS. Our data suggest that flow patterns profoundly change mitochondrial fusion/fission events, and this change contributes to the determination of proinflammatory and metabolic states of ECs.

A brief descriptive outline of the rules of mixed martial arts and concussion in mixed martial arts.

Mixed martial arts (MMA), a combat sport consisting of wrestling, boxing, and martial arts, is a popular activity associated with danger and violence. Of concern are the repetitive head impacts, both subconcussive and concussive, sustained by MMA athletes. The rules of MMA encourage head strikes, but there was no formal concussion protocol in the Ultimate Fighting Championship (UFC) until 2021. Because the UFC was established less than 30 years, the long-term consequences of these repetitive concussive head blows are lacking. In this review, we focus on current literature sought to summarize the current knowledge of repetitive head impacts and concussions in MMA. The objectives were to outline (a) the rules of MMA; (b) the postconcussion protocol for UFC athletes; (c) current behavioral and biochemical diagnostic measures; (d) epidemiology and prevalence of concussion in MMA; (e) long-term effects of subconcussive repetitive head impacts; (f) biomechanics of head impacts; and (g) considerations and research topics that warrant future research.

Molecular Detection of Equine Adenovirus 1 in Nasal Swabs from Horses in the Republic of Korea.

Equine adenovirus 1 (EAdV-1) can cause upper respiratory disease in horses and has been reported worldwide. In this study, and for the first time in Korea, the prevalence of EAdV-1 in equine nasal swabs was investigated using a PCR to identify potential risk factors and examine the genetic diversity of its DNA sequences by a comparison with foreign strains. Nasal swabs collected from 359 horses reared at Korea Racing Authority facilities were tested using an EAdV-1 hexon-specific PCR and the associations between EAdV-1 infection and sex, age, region, breed, and activity were analyzed. Five samples (1.4%, 5/359) tested positive for EAdV-1; however, no statistically significant differences were observed with respect to any variable. Among the five EAdV-1-positive horses, a co-infection with equine influenza, equine herpesvirus 1 and 4, or Streptococcus equi was not detected; however, clinical respiratory signs were observed in one. Phylogenetic analyses based on partial EAdV-1 hexon gene sequences revealed that the Korean EAdV-1 isolates shared approximately 98.8-100% similarity among each other and with foreign strains. Three Korean isolates shared high similarity with strains from Australia and India and the remaining two isolates were separate in phylogenetic analyses. These findings highlight the molecular prevalence and genetic diversity of EAdV-1 in horses in Korea.

Healthy versus Unhealthy Adipose Tissue Expansion: the Role of Exercise.

Although the hallmark of obesity is the expansion of adipose tissue, not all adipose tissue expansion is the same. Expansion of healthy adipose tissue is accompanied by adequate capillary angiogenesis and mitochondria-centered metabolic integrity, whereas expansion of unhealthy adipose tissue is associated with capillary and mitochondrial derangement, resulting in deposition of immune cells (M1-stage macrophages) and excess production of pro-inflammatory cytokines. Accumulation of these dysfunctional adipose tissues has been linked to the development of obesity comorbidities, such as type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease, which are leading causes of human mortality and morbidity in modern society. Mechanistically, vascular rarefaction and mitochondrial incompetency (for example, low mitochondrial content, fragmented mitochondria, defective mitochondrial respiratory function, and excess production of mitochondrial reactive oxygen species) are frequently observed in adipose tissue of obese patients. Recent studies have demonstrated that exercise is a potent behavioral intervention for preventing and reducing obesity and other metabolic diseases. However, our understanding of potential cellular mechanisms of exercise, which promote healthy adipose tissue expansion, is at the beginning stage. In this review, we hypothesize that exercise can induce unique physiological stimuli that can alter angiogenesis and mitochondrial remodeling in adipose tissues and ultimately promote the development and progression of healthy adipogenesis. We summarize recent reports on how regular exercise can impose differential processes that lead to the formation of either healthy or unhealthy adipose tissue and discuss key knowledge gaps that warrant future research.

Mitochondrial and Metabolic Adaptations to Exercise-Induced Fluid Shear Stress in Endothelial Cells.

Recent studies have greatly advanced our understanding of the central role of mitochondria on endothelial function. Here, we propose a hypothesis that unidirectional laminar (pulsatile) flow and disturbed laminar (oscillatory) flow may differentially modulate mitochondrial phenotypes in the context of their bioenergetic, signaling, and biosynthetic functions, providing novel insights into subcellular mechanisms underlying how exercise benefits the improvement of vascular health.

Flow-induced endothelial mitochondrial remodeling mitigates mitochondrial reactive oxygen species production and promotes mitochondrial DNA integrity in a p53-dependent manner.

Tumor suppressor p53 plays a pivotal role in orchestrating mitochondrial remodeling by regulating their content, fusion/fission processes, and intracellular signaling molecules that are associated with mitophagy and apoptosis pathways. In order to determine a molecular mechanism underlying flow-mediated mitochondrial remodeling in endothelial cells, we examined, herein, the role of p53 on mitochondrial adaptations to physiological flow and its relevance to vascular function using endothelial cell-specific p53 deficient mice. We observed no changes in aerobic capacity, basal blood pressure, or endothelial mitochondrial phenotypes in the endothelial p53 mull animals. However, after 7 weeks of voluntary wheel running exercise, blood pressure reduction and endothelial mitochondrial remodeling (biogenesis, elongation, and mtDNA replication) were substantially blunted in endothelial p53 null animals compared to the wild-type, subjected to angiotensin II-induced hypertension. In addition, endothelial mtDNA lesions were significantly reduced following voluntary running exercise in wild-type mice, but not in the endothelial p53 null mice. Moreover, in vitro studies demonstrated that unidirectional laminar flow exposure significantly increased key putative regulators for mitochondrial remodeling and reduced mitochondrial reactive oxygen species generation and mtDNA damage in a p53-dependent manner. Mechanistically, unidirectional laminar flow instigated translocalization of p53 into the mitochondrial matrix where it binds to mitochondrial transcription factor A, TFAM, resulting in improving mtDNA integrity. Taken together, our findings suggest that p53 plays an integral role in mitochondrial remodeling under physiological flow condition and the flow-induced p53-TFAM axis may be a novel molecular intersection for enhancing mitochondrial homeostasis in endothelial cells.

Dichloromethane fractions of Calystegia soldanella induce S­phase arrest and apoptosis in HT­29 human colorectal cancer cells.

Calystegia soldanella is a halophyte and a perennial herb that grows on coastal sand dunes worldwide. Extracts from this plant have been previously revealed to have a variety of bioactive properties in humans. However, their effects on colorectal cancer cells remain poorly understood. In the present study, the potential biological activity of C. soldanella extracts in the colorectal cancer cell line HT­29 was examined. First, five solvent fractions [n­hexane, dichloromethane (DCM), ethyl acetate, n­butanol and water] were obtained from the crude extracts of C. soldanella through an organic solvent extraction method. In particular, the DCM fraction was demonstrated to exert marked dose­ and time­dependent inhibitory effects according to results from the cell viability assay. Data obtained from the apoptosis assay suggested that the inhibition of HT­29 cell viability induced by DCM treatment was attributed to increased apoptosis. The apoptotic rate was markedly increased in a dose­dependent manner, which was associated with the protein expression levels of apoptosis­related proteins, including increased Fas, Bad and Bax, and decreased pro­caspase­8, Bcl­2, Bcl­xL, pro­caspase­9, pro­caspase­7 and pro­caspase­3. A mitochondrial membrane potential assay demonstrated that more cells became depolarized and the extent of cytochrome c release was markedly increased in a dose­dependent manner in HT­29 cells treated with DCM. In addition, cell cycle analysis confirmed S­phase arrest following DCM fraction treatment, which was associated with decreased protein expression levels of cell cycle­related proteins, such as cyclin A, CDK2, cell division cycle 25 A and cyclin dependent kinase inhibitor 1. Based on these results, the present study suggested that the DCM fraction of the C. soldanella extract can inhibit HT­29 cell viability whilst inducing apoptosis through mitochondrial membrane potential regulation and S­phase arrest. These results also suggested that the DCM fraction has potential anticancer activity in HT­29 colorectal cells. Further research on the composition of the DCM fraction is warranted.

ERK phosphorylation disrupts the intramolecular interaction of capicua to promote cytoplasmic translocation of capicua and tumor growth.

Activation of receptor tyrosine kinase signaling inactivates capicua (CIC), a transcriptional repressor that functions as a tumor suppressor, via degradation and/or cytoplasmic translocation. Although CIC is known to be inactivated by phosphorylation, the mechanisms underlying the cytoplasmic translocation of CIC remain poorly understood. Therefore, we aimed to evaluate the roles of extracellular signal-regulated kinase (ERK), p90RSK, and c-SRC in the epidermal growth factor receptor (EGFR) activation-induced cytoplasmic translocation of CIC and further investigated the molecular basis for this process. We found that nuclear ERK induced the cytoplasmic translocation of CIC-S. We identified 12 serine and threonine (S/T) residues within CIC, including S173 and S301 residues that are phosphorylated by p90RSK, which contribute to the cytoplasmic translocation of CIC-S when phosphorylated. The amino-terminal (CIC-S-N) and carboxyl-terminal (CIC-S-C) regions of CIC-S were found to interact with each other to promote their nuclear localization. EGF treatment disrupted the interaction between CIC-S-N and CIC-S-C and induced their cytoplasmic translocation. Alanine substitution for the 12 S/T residues blocked the cytoplasmic translocation of CIC-S and consequently enhanced the tumor suppressor activity of CIC-S. Our study demonstrates that ERK-mediated disruption of intramolecular interaction of CIC is critical for the cytoplasmic translocation of CIC, and suggests that the nuclear retention of CIC may represent a strategy for cancer therapy.

Association of Eating Alone with Depressive Symptoms and Suicidal Ideation among Korean Adults.

BACKGROUND: In recent years, eating dinner alone has become a rising social issue in Korea. Depression is one of the primary health problems that can lead to numerous negative consequences. However, few studies have focused on people who eat alone and the effect of eating alone on depression. We investigated the association between eating dinner alone and depression. METHODS: Our cross-sectional study included data from 14,093 Korean adults aged above 19 years old; data were sourced from the Korea National Health and Nutrition Examination Survey in 2014, 2016, and 2018, when the Patient Health Questionnaire (PHQ-9) was used. We classified participants based on their dinner habits: eating alone or social eating. Depression and suicidal ideation among participants were measured using the PHQ-9. Multivariate logistic regression analysis was used to investigate whether eating alone was related to depression or suicidal ideation after adjusting for age, sex, household income, education, alcohol, smoking, exercise, frequency of eating out, and living arrangement. RESULTS: Individuals who ate dinner alone (22.9%) had higher depression and suicidal ideation rates than those who ate with others. Those who ate alone had greater odds ratios (ORs) of depressive symptoms (depression: OR, 1.42; 95% confidence interval [CI], 1.27-1.58; suicidal ideation: OR, 1.49; 95% CI, 1.25-1.78) after adjustment for covariates. The subgroup analysis shows that the odds of suicidal ideation among individuals who eat alone were nonexistent among those who performed regular aerobic exercise. CONCLUSION: Eating dinner alone is closely associated with depressive symptoms, particularly suicidal ideation. Therefore, providing opportunities to eat with others may be effective for maintaining the mental health of adults.

A Landslide Monitoring System for Natural Terrain in Korea: Development and Application in Hazard Evaluations.

This study describes the development of a landslide monitoring system for the purpose of reducing damages caused by landslides in natural terrain. The system was developed to analyze the effects of landslide-inducing rainfall and the behavior of slopes through 12 monitoring stations that are distributed across eight national parks in Korea. Several sensors and a data acquisition equipment to monitor landslide were installed in each station. The composition of the system and its operating program were designed to efficiently manage the sizeable amounts of real-time monitoring data that are collected from the various stations. To test the potential of the developed system for reliable landslide hazard evaluations, data measured over a five-year period by the two monitoring stations in Jirisan National Park were analyzed. Subsequently, the suction stress of the soil over the monitoring period was calculated by applying laboratory test result of the geotechnical and unsaturated soil properties in the analysis domain area. The infinite slope stability analysis combined with an effective stress concept based on the suction stress was applied to calculate the factor of safety. This method also enabled the temporal and quantitative evaluation of slope stability in natural terrain. In addition, based on the monitoring and slope stability analysis results, an analysis for the spatial classification of landslide hazards was conducted. The analysis results quantitatively and statistically demonstrated that 98% of historical landslide initiation areas were classified as high hazard levels.

Effect of Aging on Homeostasis in the Soft Tissue of the Periodontium: A Narrative Review.

Aging is characterized by a progressive decline or loss of physiological functions, leading to increased susceptibility to disease or death. Several aging hallmarks, including genomic instability, cellular senescence, and mitochondrial dysfunction, have been suggested, which often lead to the numerous aging disorders. The periodontium, a complex structure surrounding and supporting the teeth, is composed of the gingiva, periodontal ligament, cementum, and alveolar bone. Supportive and protective roles of the periodontium are very critical to sustain life, but the periodontium undergoes morphological and physiological changes with age. In this review, we summarize the current knowledge of molecular and cellular physiological changes in the periodontium, by focusing on soft tissues including gingiva and periodontal ligament.

Adaptive Immune Response Signaling Is Suppressed in Ly6Chigh Monocyte but Upregulated in Monocyte Subsets of ApoE-/- Mice - Functional Implication in Atherosclerosis.

Rationale: Inflammatory monocyte (MC) subset differentiation is a major feature in tissue inflammatory and atherosclerosis. The underlying molecular mechanism remains unclear. Objective: This study aims to explore molecule targets and signaling which determinate immunological features in MC subsets. Methods and Results: Blood Ly6Chigh and Ly6Clow MC subsets from control and ApoE-/- mice were isolated by flow cytometry sorting and subjected for bulk high-throughput RNA-sequencing. Intensive bioinformatic studies were performed by analyzing transcriptome through four pairs of comparisons: A) Ly6Chigh vs Ly6Clow in control mice; B) Ly6Chigh vs Ly6Clow in ApoE-/- mice; C) ApoE-/- Ly6Chigh vs control Ly6Chigh MC; D) ApoE-/- Ly6Clow vs control Ly6Clow MC. A total of 80 canonical pathways and 16 enriched pathways were recognized by top-down analysis using IPA and GSEA software, and further used for overlapping analysis. Immunological features and signaling were assessed on four selected functional groups, including MHCII, immune checkpoint, cytokine, and transcription factor (TF). Among the total 14578 significantly differentially expressed (SDE) genes identified though above four comparison, 1051 TF and 348 immunological genes were discovered. SDE immunological genes were matched with corresponding upstream SDE TF by IPA upstream analysis. Fourteen potential transcriptional axes were recognized to modulate immunological features in the Ly6C MC subset. Based on an intensive literature search, we found that the identified SDE immune checkpoint genes in Ly6Chigh MC are associated with pro-inflammatory/atherogenic balance function. Immune checkpoint genes GITR, CTLA4, and CD96 were upregulated in Ly6Clow MC from all mice and presented anti-inflammatory/atherogenic features. Six cytokine genes, including Ccl2, Tnfsf14, Il1rn, Cxcl10, Ccl9, and Cxcl2, were upregulated in Ly6Chigh MC from all mice and associated with pro-inflammatory/atherogenic feature. Cytokine receptor gene Il12rb2, Il1r1, Il27ra, Il5ra, Ngfr, Ccr7, and Cxcr5 were upregulated in Ly6Clow MC from all mice and presented anti-inflammatory/atherogenic features. MHCII genes (H2-Oa, H2-DMb2, H2-Ob, H2-Eb2, H2-Eb1, H2-Aa, and Cd74) were elevated in Ly6Clow MC from all mice. ApoE-/- augmented pro-atherogenic/inflammatory and antigen-presenting cells (APC) feature in both subsets due to elevated expression of cytokine genes (Cxcl11, Cntf, Il24, Xcl, Ccr5, Mpl, and Acvr2a) and MHCII gene (H2-Aa and H2-Ea-ps). Finally, we modeled immunological gene expression changes and functional implications in MC differentiation and adaptive immune response for MC subsets from control and ApoE-/- mice. Conclusions: Ly6Chigh MC presented pro-inflammatory/atherogenic features and lower APC potential. Ly6Clow MC displayed anti-inflammatory/atherogenic features and higher APC potential. ApoE-/- confers upon both subsets with augmented pro-atherogenic/inflammatory function and APC potential.

Prevalence and characterization of Clostridium perfringens isolated from feces of captive cynomolgus monkeys (Macaca fascicularis).

Clostridium perfringens is ubiquitous in the environment and the gastrointestinal tract of warm-blooded animals. While part of the gut microbiome, abnormal growth of C. perfringens causes histotoxic, neurologic, and enteric diseases in a variety of animal species, including humans, due to the production of toxins. There is extremely limited information on C. perfringens infection in non-human primates. Presently, 10 strains were successfully isolated from 126 monkeys and confirmed by molecular and biochemical analyses. All isolates were genotype A based on molecular analysis. Alpha toxin was identified in all isolates. Beta 2 toxin was detected in only three isolates. No other toxins, including enterotoxin, beta, iota, epsilon, and net B toxin, were identified in any isolate. All isolates were highly susceptible to ß-lactam antibiotics. Double hemolysis and lecithinase activity were commonly observed in all strains. Biofilm formation, which can increase antibiotic resistance, was identified in 90% of the isolates. The data are the first report the prevalence and characteristics of C. perfringens isolated from captive cynomolgus monkeys.

Infusion of Plasma from Exercised Mice Ameliorates Cognitive Dysfunction by Increasing Hippocampal Neuroplasticity and Mitochondrial Functions in 3xTg-AD Mice.

Alzheimer's disease is the most common neurodegenerative brain disease causing dementia. It is characterized by slow onset and gradual worsening of memory and other cognitive functions. Recently, parabiosis and infusion of plasma from young mice have been proposed to have positive effects in aging and Alzheimer's disease. Therefore, this study examined whether infusion of plasma from exercised mice improved cognitive functions related to the hippocampus in a 3xTg-Alzheimer's disease (AD) model. We collected plasma from young mice that had exercised for 3 months and injected 100 µL of plasma into the tail vein of 12-month-old 3xTg-AD mice 10 times at 3-day intervals. We then analyzed spatial learning and memory, long-term memory, hippocampal GSK3ß/tau proteins, synaptic proteins, mitochondrial function, apoptosis, and neurogenesis. In the hippocampus of 3xTg-AD mice, infusion of plasma from exercised mice improved neuroplasticity and mitochondrial function and suppressed apoptosis, ultimately improving cognitive function. However, there was no improvement in tau hyperphosphorylation. This study showed that plasma from exercised mice could have a protective effect on cognitive dysfunction and neural circuits associated with AD via a tau-independent mechanism involving elevated brain-derived neurotrophic factor due to exercise.

Exercise training ameliorates cerebrovascular dysfunction in a murine model of Alzheimer's disease: role of the P2Y2 receptor and endoplasmic reticulum stress.

Cerebrovascular dysfunction is a critical risk factor for the pathogenesis of Alzheimer's disease (AD). The purinergic P2Y2 receptor and endoplasmic reticulum (ER) stress are tightly associated with vascular dysfunction and the pathogenesis of AD. However, the protective effects of exercise training on P2Y2 receptor- and ER stress-associated cerebrovascular dysfunction in AD are mostly unknown. Control (C57BL/6, CON) and AD (APP/PS1dE9, AD) mice underwent treadmill exercise training (EX). 2-MeS-ATP-induced dose-dependent vasoreactivity was determined by using a pressurized posterior cerebral artery (PCA) from 10-12-mo-old mice. Human brain microvascular endothelial cells (HBMECs) were exposed to laminar shear stress (LSS) at 20 dyn/cm2 for 30 min, 2 h, and 24 h. The expression of P2Y2 receptors, endothelial nitric oxide synthase (eNOS), and ER stress signaling were quantified by Western blot analysis. Notably, exercise converted ATP-induced vasoconstriction in the PCA from AD mice to vasodilation in AD+EX mice to a degree commensurate to the vascular reactivity observed in CON mice. Exercise reduced the expression of amyloid peptide precursor (APP) and increased the P2Y2 receptor and Akt/eNOS expression in AD mice brain. Mechanistically, LSS increased the expression of both P2Y2 receptor and eNOS protein in HBMECs, but these increases were blunted by a P2Y2 receptor antagonist in HBMECs. Exercise also reduced the expression of aberrant ER stress markers p-IRE1, p/t-eIF2α, and CHOP, as well as Bax/Bcl-2, in AD mice brain. Collectively, our results demonstrate for the first time that exercise mitigates cerebrovascular dysfunction in AD through modulating P2Y2 receptor- and ER stress-dependent endothelial dysfunction.NEW & NOTEWORTHY A limited study has investigated whether exercise training can improve cerebrovascular function in Alzheimer's disease. The novel findings of the study are that exercise training improves cerebrovascular dysfunction through enhancing P2Y2 receptor-mediated eNOS signaling and reducing ER stress-associated pathways in AD. These data suggest that exercise training, which regulates P2Y2 receptor and ER stress in AD brain, is a potential therapeutic strategy for Alzheimer's disease.

Unlocking the Secrets of Mitochondria in the Cardiovascular System: Path to a Cure in Heart Failure­A Report from the 2018 National Heart, Lung, and Blood Institute Workshop

Mitochondria have emerged as a central factor in the pathogenesis and progression of heart failure, and other cardiovascular diseases, as well, but no therapies are available to treat mitochondrial dysfunction. The National Heart, Lung, and Blood Institute convened a group of leading experts in heart failure, cardiovascular diseases, and mitochondria research in August 2018. These experts reviewed the current state of science and identified key gaps and opportunities in basic, translational, and clinical research focusing on the potential of mitochondria-based therapeutic strategies in heart failure. The workshop provided short- and long-term recommendations for moving the field toward clinical strategies for the prevention and treatment of heart failure and cardiovascular diseases by using mitochondria-based approaches.

Subsidence and perioperative periprosthetic fractures using collarless hydroxyapatite-coated stem for displaced femoral neck fractures according to Dorr type.

BACKGROUND: Hydroxyapatite (HA)-coated stem has been introduced to decrease complications and eventually achieve quicker implant ingrowth and long-term stability. The aim of this study was to determine subsidence rate and incidence of perioperative periprosthetic fracture (PPF) of uncemented collarless Corail stem for displaced femoral neck fractures according to Dorr type. METHODS: A retrospective review of plain radiographs and clinical data was carried out to identify consecutive patients who underwent uncemented hip hemiarthroplasty using collarless HA-coated Corail stem between March 2010 and August 2014. The risk of subsidence and PPF according to Dorr type was evaluated. RESULTS: Dorr types A, B, and C were found in 66 (median age 74, 29.7%), 107 (median age 77, 48.2%), and 49 (median age 80, 22.1%) cases, respectively. Subsidence of stem occurred in eight (3.6%) cases. Dorr type had significant relationship (p < 0.05) with subsidence. Type C canals had higher rates of subsidence. PPFs occurred in 11 (5.0%) cases without showing significant difference among Dorr types not significant (n.s.). Female gender was not influential on subsidence (n.s.) and PPF (n.s.). CONCLUSION: Dorr type C had higher risk of subsidence when using uncemented collarless HA-coated stem. Dorr canal type had no bearing on risk of PPFs. Women did not have significantly higher risk of both subsidence and PPFs compared to men. A collarless fully HA-coated Corail stem had 3.6% of radiological subsidence and 5.0% of PPF risk.

Sustained Delivery of Carfilzomib by Tannic Acid-Based Nanocapsules Helps Develop Antitumor Immunity.

A group of chemotherapeutic drugs has gained increasing interest in cancer immunotherapy due to the potential to induce immunogenic cell death (ICD). A critical challenge in using the ICD inducers in cancer immunotherapy is the immunotoxicity accompanying their antiproliferative effects. To alleviate this, a nanocapsule formulation of carfilzomib (CFZ), an ICD-inducing proteasome inhibitor, was developed using interfacial supramolecular assembly of tannic acid (TA) and iron, supplemented with albumin coating. The albumin-coated CFZ nanocapsules (CFZ-pTA-alb) attenuated CFZ release, reducing toxicity to immune cells. Moreover, due to the adhesive nature of the TA assembly, CFZ-pTA-alb served as a reservoir of damage-associated molecular patterns released from dying tumor cells to activate dendritic cells. Upon intratumoral administration, CFZ-pTA-alb prolonged tumor retention of CFZ and showed consistently greater antitumor effects than cyclodextrin-solubilized CFZ (CFZ-CD) in B16F10 and CT26 tumor models. Unlike CFZ-CD, the locally injected CFZ-pTA-alb protected or enhanced CD8+ T cell population in tumors, helped develop splenocytes with tumor-specific interferon-γ response, and delayed tumor development on the contralateral side in immunocompetent mice (but not in athymic nude mice), supporting that CFZ-pTA-alb contributed to activating antitumor immunity. This study demonstrates that sustained delivery of ICD inducers by TA-based nanocapsules is an effective way of translating local ICD induction to systemic antitumor immunity.