How close is autophagy-targeting therapy for Alzheimer's disease to clinical use? A summary of autophagy modulators in clinical studies.

Alzheimer's disease (AD) is a neurodegenerative disorder clinically characterized by progressive decline of memory and cognitive functions, and it is the leading cause of dementia accounting for 60%-80% of dementia patients. A pathological hallmark of AD is the accumulation of aberrant protein/peptide aggregates such as extracellular amyloid plaques containing amyloid-beta peptides and intracellular neurofibrillary tangles composed of hyperphosphorylated tau. These aggregates result from the failure of the proteostasis network, which encompasses protein synthesis, folding, and degradation processes.

Surgically treated purulent pericarditis induced by ingested fish bone: a case report.

Background: Aspiration of fish bones is common, but perforation of the gastrointestinal tract is very rare. Once perforation occurs, fatal complications such as mediastinitis and cardiac tamponade can occur. Here, we present a case of acute pericarditis due to perforation of a fish bone.

Endoleak after use of the fenestrated frozen elephant trunk technique to treat acute type A aortic dissection.

Several studies have indicated that the fenestrated frozen elephant trunk (FET) technique enhances early outcomes in cases of acute aortic dissection, although long-term outcomes remain unclear. A case involving a 62-year-old male who experienced endoleak from a fenestration site following total arch replacement using the fenestrated FET technique for a DeBakey type I aortic dissection is reported. The patient underwent successful reoperation involving total arch replacement and reinsertion of the FET.

Embolization of left anterior descending artery due to pledget after a redo surgery.

A 53-year-old man underwent aortic root replacement for acute aortic dissection. Following this procedure, the patient developed a pseudoaneurysm at the aortic root, necessitating reoperation. The subsequent surgery was performed routinely, allowing the patient to be weaned from mechanical ventilation on the same day.

Sutureless Repair for Iliac Vein Bleeding Using an Elastomeric Sealant.

Addressing venous bleeding is a frequent complication of vascular and abdominopelvic surgeries. We present a novel sutureless repair technique using Hydrofit (Terumo, Tokyo, Japan), an elastomeric sealant. In a patient experiencing common iliac vein bleeding during abdominal aortic aneurysm surgery, this technique successfully achieved complete hemostasis.

Severe right ventricular infarction due to iatrogenic aortocoronary dissection successfully treated by surgical repair and extracorporeal membrane oxygenation.

Iatrogenic aortocoronary dissection (IACD) is a rare but potentially fatal complication of percutaneous coronary intervention or coronary angiography (CAG). In particular, if the condition of the patient is complicated by cardiogenic shock and right ventricular (RV) dysfunction, the mortality rate is high. Herein, we report the case of an 85-year-old woman with IACD who underwent elective CAG of the right coronary artery complicated with cardiogenic shock due to RV infarction.

Mitochondrial hypermetabolism precedes impaired autophagy and synaptic disorganization in App knock-in Alzheimer mouse models.

Accumulation of amyloid β-peptide (Aβ) is a driver of Alzheimer's disease (AD). Amyloid precursor protein (App) knock-in mouse models recapitulate AD-associated Aβ pathology, allowing elucidation of downstream effects of Aβ accumulation and their temporal appearance upon disease progression. Here we have investigated the sequential onset of AD-like pathologies in App and App knock-in mice by time-course transcriptome analysis of hippocampus, a region severely affected in AD.

The Expression of the Endocannabinoid Receptors CB2 and GPR55 Is Highly Increased during the Progression of Alzheimer's Disease in Knock-In Mice.

Background: The endocannabinoid system (ECS) and associated lipid transmitter-based signaling systems play an important role in modulating brain neuroinflammation. ECS is affected in neurodegenerative disorders, such as Alzheimer's disease (AD). Here we have evaluated the non-psychotropic endocannabinoid receptor type 2 (CB2) and lysophosphatidylinositol G-protein-coupled receptor 55 (GPR55) localization and expression during Aβ-pathology progression.

Identification of glycolytic proteins as binding partners of Bri2 BRICHOS domain.

Human integral membrane protein 2B (ITM2B or Bri2) is a member of the BRICHOS family, that can attenuate Aβ pathology in the brain. As a result, the identification of novel Bri2 BRICHOS client proteins has been sought to help elucidate signaling pathways and the potential identification of novel therapeutic targets. To identify Bri2 BRICHOS interacting partners, we carried out a 'protein fishing' experiment using recombinant human (rh) Bri2 BRICHOS-coated magnetic particles, in combination with proteomic analysis on cytosolic and membrane fractions of cortical homogenates from C57BL/6 J WT mouse.

Identification of cytoskeletal proteins as binding partners of Bri2 BRICHOS domain.

Proteins must fold into three-dimensional structures to execute their biological functions. Therefore, maintenance of protein homeostasis, proteostasis, including prevention of protein misfolding is essential for cellular activity and health. Molecular chaperones are key actors in proteostasis.

[A Case of Laparoscopic Total Gastrectomy for Juvenile Polyposis of Stomach with Synchronous Multiple Intramucosal Carcinomas].

The patient was a 57-year-old woman. She was referred to our hospital because severe anemia. Upper gastrointestinal endoscopy revealed polyposis throughout the stomach and lobulated polyps in cardia, greater curve of middle body of the stomach, and angulus.

Autophagy Impairment in Knock-in Alzheimer's Model Mice.

Alzheimer's disease (AD) is characterized by impaired protein homeostasis leading to amyloid-β peptide (Aβ) amyloidosis. Amyloid precursor protein (APP) knock-in mice exhibit robust Aβ pathology, providing possibilities to determine its effect on protein homeostasis including autophagy. Here we compared human AD postmortem brain tissue with brains from two different types of knock-in mice, and mice, exhibiting AD-like pathology.

Benefits of amplification for unaided speech discrimination in age-related hearing loss with flat type audiogram.

Objective: The present study aimed to investigate whether hearing aid use can induce improvement as acclimatization effect in unaided speech perception in patients with age-related hearing loss.

Methods: Fifty ears in 41 patients (age range: 65-91 years) diagnosed as age-related hearing loss were enrolled in this study. They used hearing aids for more than 8 hours per day.

Plasma membrane phosphatidylinositol (4,5)-bisphosphate is critical for determination of epithelial characteristics.

Epithelial cells provide cell-cell adhesion that is essential to maintain the integrity of multicellular organisms. Epithelial cell-characterizing proteins, such as epithelial junctional proteins and transcription factors are well defined. However, the role of lipids in epithelial characterization remains poorly understood.

An App knock-in rat model for Alzheimer's disease exhibiting Aβ and tau pathologies, neuronal death and cognitive impairments.

A major obstacle in Alzheimer's disease (AD) research is the lack of predictive and translatable animal models that reflect disease progression and drug efficacy. Transgenic mice overexpressing amyloid precursor protein (App) gene manifest non-physiological and ectopic expression of APP and its fragments in the brain, which is not observed in AD patients. The App knock-in mice circumvented some of these problems, but they do not exhibit tau pathology and neuronal death.

Neuronal cell-based high-throughput screen for enhancers of mitochondrial function reveals luteolin as a modulator of mitochondria-endoplasmic reticulum coupling.

Background: Mitochondrial dysfunction is a common feature of aging, neurodegeneration, and metabolic diseases. Hence, mitotherapeutics may be valuable disease modifiers for a large number of conditions. In this study, we have set up a large-scale screening platform for mitochondrial-based modulators with promising therapeutic potential.

Benzimidazole-based fluorophores for the detection of amyloid fibrils with higher sensitivity than Thioflavin-T.

Protein aggregation into amyloid fibrils is a key feature of a multitude of neurodegenerative diseases such as Alzheimer's, Parkinson's, and Prion disease. To detect amyloid fibrils, fluorophores with high sensitivity and better efficiency coupled with the low toxicity are in high demand even to date. In this pursuit, we have unveiled two benzimidazole-based fluorescence sensors ([C H N ] (C1) and [C H N O ] (C2), which possess exceptional affinity toward different amyloid fibrils in its submicromolar concentration (8 × 10  M), whereas under a similar concentration, the gold standard Thioflavin-T (ThT) fails to bind with amyloid fibrils.

Phosphatidylinositol 4,5-bisphosphate is localized in the plasma membrane outer leaflet and regulates cell adhesion and motility.

Phospholipids are distributed asymmetrically in the plasma membrane (PM) of mammalian cells. Phosphatidylinositol (PI) and its phosphorylated forms are primarily located in the inner leaflet of the PM. Among them, phosphatidylinositol 4,5-bisphosphate (PI(4,5)P) is a well-known substrate for phospholipase C (PLC) or phosphoinositide-3 kinase, and is also a regulator for the actin cytoskeleton or ion channels.

Thermal-transport studies of kagomé antiferromagnets.

Searching for the ground state of a kagomé Heisenberg antiferromagnet (KHA) has been one of the central issues of condensed-matter physics, because the KHA is expected to host spin-liquid phases with exotic elementary excitations. Here, we show our longitudinal ([Formula: see text]) and transverse ([Formula: see text]) thermal conductivities measurements of the two kagomé materials, volborthite and Ca kapellasite. Although magnetic orders appear at temperatures much lower than the antiferromagnetic energy scale in both materials, the nature of spin liquids can be captured above the transition temperatures.

Spin Thermal Hall Conductivity of a Kagome Antiferromagnet.

A clear thermal Hall signal (κ_{xy}) was observed in the spin-liquid phase of the S=1/2 kagome antiferromagnet Ca kapellasite [CaCu_{3}(OH)_{6}Cl_{2}·0.6H_{2}O]. We found that κ_{xy} is well reproduced, both qualitatively and quantitatively, using the Schwinger-boson mean-field theory with the Dzyaloshinskii-Moriya interaction of D/J∼0.

Unusual Thermal Hall Effect in a Kitaev Spin Liquid Candidate α-RuCl_{3}.

The Kitaev quantum spin liquid displays the fractionalization of quantum spins into Majorana fermions. The emergent Majorana edge current is predicted to manifest itself in the form of a finite thermal Hall effect, a feature commonly discussed in topological superconductors. Here we report on thermal Hall conductivity κ_{xy} measurements in α-RuCl_{3}, a candidate Kitaev magnet with the two-dimensional honeycomb lattice.

Anomalous Change in the de Haas-van Alphen Oscillations of CeCoIn_{5} at Ultralow Temperatures.

We perform de Haas-van Alphen (dHvA) measurements of the heavy-fermion superconductor CeCoIn_{5} down to 2 mK above the upper critical field. We find that the dHvA amplitudes show an anomalous suppression, concomitantly with a shift of the dHvA frequency, below the transition temperature T_{n}=20  mK. We suggest that the change is owing to magnetic breakdown caused by a field-induced antiferromagnetic (AFM) state emerging below T_{n}, revealing the origin of the field-induced quantum critical point (QCP) in CeCoIn_{5}.