Amyloid beta oligomers-induced parkin aggravates ER stress-mediated cell death through a positive feedback loop.

Recently, Parkin has been reported to induce endoplasmic reticulum (ER) stress. In addition, amyloid beta oligomers (AβO), hallmarks of Alzheimer's disease (AD), also increase ER stress in neurons. Because a mutation in the Parkin gene is a well-known predominant cause of familial Parkinson's disease (PD), Parkin has been well studied in PD but has not been well researched in AD.

Establishment and Characterization of Immortalized Miniature Pig Pancreatic Cell Lines Expressing Oncogenic K-Ras.

In recent decades, many studies on the treatment and prevention of pancreatic cancer have been conducted. However, pancreatic cancer remains incurable, with a high mortality rate. Although mouse models have been widely used for preclinical pancreatic cancer research, these models have many differences from humans.

Amyloid-beta oligomers induce Parkin-mediated mitophagy by reducing Miro1.

Alzheimer's disease (AD) is a neurodegenerative disease associated with the accumulation of amyloid-beta oligomers (AβO). Recent studies have demonstrated that mitochondria-specific autophagy (mitophagy) contributes to mitochondrial quality control by selectively eliminating the dysfunctional mitochondria. Mitochondria motility, which is regulated by Miro1, is also associated with neuronal cell functions.

Isoliquiritigenin Reduces LPS-Induced Inflammation by Preventing Mitochondrial Fission in BV-2 Microglial Cells.

Excessive microglial cell activation in the brain can lead to the production of various neurotoxic factors (e.g., pro-inflammatory cytokines, nitric oxide) which can, in turn, initiate neurodegenerative processes.

Peroxiredoxin 5 deficiency exacerbates iron overload-induced neuronal death via ER-mediated mitochondrial fission in mouse hippocampus.

Iron is an essential element for cellular functions, including those of neuronal cells. However, an imbalance of iron homeostasis, such as iron overload, has been observed in several neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease. Iron overload causes neuronal toxicity through mitochondrial fission, dysregulation of Ca, ER-stress, and ROS production.

Peroxiredoxin 5 prevents diethylhexyl phthalate-induced neuronal cell death by inhibiting mitochondrial fission in mouse hippocampal HT-22 cells.

Diethylhexyl phthalate (DEHP) is used in many plastic products, such as perfumes, lunch boxes, bags, and building materials. As DEHP is not covalently bound to the plastic, humans can be easily exposed to it. DEHP induces neurobehavioral changes and neuronal cell death; however, the exact mechanism behind this is still unclear.

Peroxiredoxin 4 ameliorates amyloid beta oligomer-mediated apoptosis by inhibiting ER-stress in HT-22 hippocampal neuron cells.

Alzheimer's disease (AD) is a neurodegenerative disorder caused by amyloid beta oligomers (AβO), which induce cell death by triggering oxidative stress and endoplasmic reticulum (ER) stress. Oxidative stress is regulated by antioxidant enzymes, including peroxiredoxins. Peroxiredoxins (Prx) are classified into six subtypes, based on their localization and cysteine residues, and protect cells by scavenging hydrogen peroxide (HO).

Peroxiredoxin I maintains luteal function by regulating unfolded protein response.

Background: Mounting evidence shows that ROS regulation by various antioxidants is essential for the expression of enzymes involved in steroidogenesis and maintenance of progesterone production by the corpus luteum (CL). However, the underlying mechanisms of peroxiredoxin 1 (PRDX1), an antioxidant enzyme, in luteal function for progesterone production in mice have not been reported. The aim of this study was to evaluate the functional link between PRDX1 and progesterone production in the CL of Prdx1 knockout (K/O) mice in the functional stage of CL.

Isoliquiritigenin attenuates glutamate-induced mitochondrial fission via calcineurin-mediated Drp1 dephosphorylation in HT22 hippocampal neuron cells.

Numerous studies suggest that glutamate toxicity is a major contributor to neuronal dysfunction and death in several neurodegenerative diseases. In our previous study, isoliquiritigenin (ISL) isolated from Glycyrrhiza uralensis showed neuroprotective effects against neuronal cell death mediated by intracellular reactive oxygen species (ROS) generation and loss of mitochondrial membrane potential. However, the mechanisms by which ISL protects against glutamate-induced oxidative stress are unknown.

Peroxiredoxin 5 prevents iron overload-induced neuronal death by inhibiting mitochondrial fragmentation and endoplasmic reticulum stress in mouse hippocampal HT-22 cells.

Iron is an essential element for neuronal as well as cellular functions. However, Iron overload has been known to cause neuronal toxicity through mitochondrial fission, dysregulation of Ca, endoplasmic reticulum (ER) stress, and reactive oxygen species (ROS) production. Nevertheless, the precise mechanisms of iron-induced oxidative stress and mitochondria- and ER-related iron toxicity in neuronal cells are not fully understood.

Peroxiredoxin 2 deficiency accelerates age-related ovarian failure through the reactive oxygen species-mediated JNK pathway in mice.

Reactive oxygen species (ROS) produced in biological reactions have been shown to contribute to ovarian aging. Peroxiredoxin 2 (Prx2) is an antioxidant enzyme that protects cells by scavenging ROS; however, its effect on age-related, oxidative stress-associated ovarian failure has not been reported. Here, we investigated its role in age-related ovarian dysfunction and 4-vinylcyclohexene diepoxide (VCD)-induced premature ovarian failure using Prx2-deficient mice.

Peroxiredoxin 5 Decreases Beta-Amyloid-Mediated Cyclin-Dependent Kinase 5 Activation Through Regulation of Ca-Mediated Calpain Activation.

Aims: Aberrant Cdk5 (cyclin-dependent kinase 5) and oxidative stress are crucial components of diverse neurodegenerative disorders, including Alzheimer's disease (AD). We previously reported that a change in peroxiredoxin (Prx) expression is associated with protection from neuronal death. The aim of the current study was to analyze the role of Prx in regulating Cdk5 activation in AD.

A Novel Urotensin II Receptor Antagonist, KR-36996 Inhibits Smooth Muscle Proliferation through ERK/ROS Pathway.

Urotensin II (UII) is a mitogenic and hypertrophic agent that can induce the proliferation of vascular cells. UII inhibition has been considered as beneficial strategy for atherosclerosis and restenosis. However, currently there is no therapeutics clinically available for atherosclerosis or restenosis.

Peroxiredoxin 5 (Prx5) decreases LPS-induced microglial activation through regulation of Ca/calcineurin-Drp1-dependent mitochondrial fission.

Microglial activation is a hallmark of neurodegenerative diseases. ROS activates microglia by regulating transcription factors to express pro-inflammatory genes and is associated with disruption of Ca homeostasis through thiol redox modulation. Recently, we reported that Prx5 can regulate activation of microglia cells by governing ROS.

Blockade of Urotensin II Receptor Prevents Vascular Dysfunction.

Urotensin II (UII) is a potent vasoactive peptide and mitogenic agent to induce proliferation of various cells including vascular smooth muscle cells (VSMCs). In this study, we examined the effects of a novel UII receptor (UT) antagonist, KR-36676, on vasoconstriction of aorta and proliferation of aortic SMCs. In rat aorta, UII-induced vasoconstriction was significantly inhibited by KR-36676 in a concentration-dependent manner.

Iron overload-induced calcium signals modulate mitochondrial fragmentation in HT-22 hippocampal neuron cells.

Iron is necessary for neuronal functions; however, excessive iron accumulation caused by impairment of iron balance could damage neurons. Neuronal iron accumulation has been observed in several neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. Nevertheless, the precise mechanisms underlying iron toxicity in neuron cells are not fully understood.

Iron overload triggers mitochondrial fragmentation via calcineurin-sensitive signals in HT-22 hippocampal neuron cells.

The accumulation of iron in neurons has been proposed to contribute to the pathology of numerous neurodegenerative diseases, such as Alzheimer's disease and Parkinson's disease. However, insufficient research has been conducted on the precise mechanism underlying iron toxicity in neurons. In this study, we investigated mitochondrial dynamics in hippocampal HT-22 neurons exposed to ferric ammonium citrate (FAC) as a model of iron overload and neurodegeneration.

Nitrogen-centered radical-mediated C-H imidation of arenes and heteroarenes via visible light induced photocatalysis.

The C-H imidation of arenes and heteroarenes has been achieved via visible light induced photocatalysis. In the presence of an iridium(III) photoredox catalyst, the reaction of aromatic substrates with N-chlorophthalimide furnishes the N-aryl products at room temperature through a nitrogen-centered radical mediated aromatic substitution.

Rhodium-catalyzed oxygenative [2 + 2] cycloaddition of terminal alkynes and imines for the synthesis of β-lactams.

A rhodium-catalyzed oxygenative [2 + 2] cycloaddition of terminal alkynes and imines has been developed, which gives β-lactams as products with high trans diastereoselectivity. In the presence of a Rh(I) catalyst and 4-picoline N-oxide, a terminal alkyne is converted to a rhodium ketene species via oxidation of a vinylidene complex and subsequently undergoes a [2 + 2] cycloaddition with an imine to give rise to the 2-azetidinone ring system. Mechanistic studies suggest that the reaction proceeds through a metalloketene rather than free ketene intermediate.

Design and validation of a general purpose robotic testing system for musculoskeletal applications.

Orthopaedic research on in vitro forces applied to bones, tendons, and ligaments during joint loading has been difficult to perform because of limitations with existing robotic simulators in applying full-physiological loading to the joint under investigation in real time. The objectives of the current work are as follows: (1) describe the design of a musculoskeletal simulator developed to support in vitro testing of cadaveric joint systems, (2) provide component and system-level validation results, and (3) demonstrate the simulator's usefulness for specific applications of the foot-ankle complex and knee. The musculoskeletal simulator allows researchers to simulate a variety of loading conditions on cadaver joints via motorized actuators that simulate muscle forces while simultaneously contacting the joint with an external load applied by a specialized robot.

Assessment of the effects of diabetes on midfoot joint pressures using a robotic gait simulator.

Background: One of the more serious diabetic complications is Charcot neuroarthropathy (CN), a disease that results in arch collapse and permanent foot deformity. However, very little is known about the etiology of CN. From a mechanical standpoint, it is likely that there is a ;;vicious circle'' in terms of (i) arch collapse causing increased midfoot joint pressures, and (ii) increased joint contact pressures exacerbating the collapse of midfoot bones.

Total synthesis of (-)-blepharocalyxin D.

[reaction: see text] The Prins cyclization strategy was successfully applied in the total synthesis of (-)-blepharocalyxin D, a cytotoxic dimeric diarylheptanoid isolated from Alpinia blepharocalyx.