Progressive iron overload in middle-aged mice impairs olfactory function, triggers lipid oxidation and induces apoptosis.

Introduction: This study aims to investigate the progressive impact of chronic iron overload on the olfactory bulb, a region significantly affected in early neurodegenerative diseases like Parkinson's and Alzheimer's. The focus is on understanding how iron accumulation leads to oxidative stress, mitochondrial dysfunction, and neuronal damage over time in middle-aged mice.

Method: The mice were continuously administered FC for a duration of 16 weeks, and the olfactory behavior of the mice was observed at intervals of 4 weeks.

Investigation the mechanism of iron overload-induced colonic inflammation following ferric citrate exposure.

Iron overload occurs due to excessive iron intake compared to the body's demand, leading to iron deposition and impairment of multiple organ functions. Our previous study demonstrated that chronic oral administration of ferric citrate (FC) caused colonic inflammatory injury. However, the precise mechanism underlying this inflammatory response remains unclear.

Neuroprotection by acrolein sequestration through exogenously applied scavengers and endogenous enzymatic enabling strategies in mouse EAE model.

We have previously shown that the pro-oxidative aldehyde acrolein is a critical factor in MS pathology. In this study, we found that the acrolein scavenger hydralazine (HZ), when applied from the day of induction, can suppress acrolein and alleviate motor and sensory deficits in a mouse experimental autoimmune encephalomyelitis (EAE) model. Furthermore, we also demonstrated that HZ can alleviate motor deficits when applied after the emergence of MS symptoms, making potential anti-acrolein treatment a more clinically relevant strategy.

α-Gal Nanoparticles in CNS Trauma: II. Immunomodulation Following Spinal Cord Injury (SCI) Improves Functional Outcomes.

Background: Previous investigations have shown that local application of nanoparticles presenting the carbohydrate moiety galactose-α-1,3-galactose (α-gal epitopes) enhance wound healing by activating the complement system and recruiting pro-healing macrophages to the injury site. Our companion in vitro paper suggest α-gal epitopes can similarly recruit and polarize human microglia toward a pro-healing phenotype. In this continuation study, we investigate the in vivo implications of α-gal nanoparticle administration directly to the injured spinal cord.

α-Gal Nanoparticles in CNS Trauma: I. In Vitro Activation of Microglia Towards a Pro-Healing State.

Background: Macrophages and microglia play critical roles after spinal cord injury (SCI), with the pro-healing, anti-inflammatory (M2) subtype being implicated in tissue repair. We hypothesize that promoting this phenotype within the post-injured cord microenvironment may provide beneficial effects for mitigating tissue damage. As a proof of concept, we propose the use of nanoparticles incorporating the carbohydrate antigen, galactose-α-1,3-galactose (α-gal epitope) as an immunomodulator to transition human microglia (HMC3) cells toward a pro-healing state.

TRIM67 Implicates in Regulating the Homeostasis and Synaptic Development of Mitral Cells in the Olfactory Bulb.

In recent years, olfactory dysfunction has attracted increasingly more attention as a hallmark symptom of neurodegenerative diseases (ND). Deeply understanding the molecular basis underlying the development of the olfactory bulb (OB) will provide important insights for ND studies and treatments. Now, with a genetic knockout mouse model, we show that TRIM67, a new member of the tripartite motif (TRIM) protein family, plays an important role in regulating the proliferation and development of mitral cells in the OB.

The contribution of initial concussive forces and resulting acrolein surge to β-amyloid accumulation and functional alterations in neuronal networks using a TBI-on-a-chip model.

Trauma-induced Alzheimer's disease (AD) is rapidly emerging as a major consequence of traumatic brain injuries (TBI), with devastating social and economic impacts. Unfortunately, few treatment options are currently available due to a limited understanding of the underlying mechanisms. A clinically-relevant, experimental model that emulates scenarios with high levels of spatial and temporal resolution is critical for demystifying the pathways of post-TBI AD.

Acute Transcriptomic and Epigenetic Alterations at T12 After Rat T10 Spinal Cord Contusive Injury.

Spinal cord injury is a severely debilitating condition affecting a significant population in the USA. Spinal cord injury patients often have increased risk of developing persistent neuropathic pain and other neurodegenerative conditions beyond the primary lesion center later in their life. The molecular mechanism conferring to the "latent" damages at distal tissues, however, remains elusive.

Andrographolide inhibits murine embryonic neuronal development through PFKFB3-mediated glycolytic pathway.

Dysregulation of neuronal development may cause neurodevelopmental disorders. However, how to regulate embryonic neuronal development and whether this regulation can be medical interrupted are largely unknown. This study aimed to investigate whether and how andrographolide (ANP) regulates embryonic neuronal development.

Ferric citrate-induced colonic mucosal damage associated with oxidative stress, inflammation responses, apoptosis, and the changes of gut microbial composition.

Ferric citrate (FC) has been used as an iron fortifier and nutritional supplement, which is reported to induce colitis in rats, however the underlying mechanism remains to be elucidated. We performed a 16-week study of FC in male healthy C57BL/6 mice (nine-month-old) with oral administration of Ctr (0.9 % NaCl), 1.

Automatic Detection and Characterization of Autonomic Dysreflexia Using Multi-Modal Non-Invasive Sensing and Neural Networks.

Autonomic dysreflexia (AD) frequently occurs in persons with spinal cord injuries (SCIs) above the T6 level triggered by different stimuli below the level of injury. If improperly managed, AD can have severe clinical consequences, even possibly leading to death. Existing techniques for AD detection are time-consuming, obtrusive, lack automated detection capabilities, and have low temporal resolution.

Ultra-short T components imaging of the whole brain using 3D dual-echo UTE MRI with rosette k-space pattern.

Purpose: This study aimed to develop a new 3D dual-echo rosette k-space trajectory, specifically designed for UTE MRI applications. The imaging of the ultra-short transverse relaxation time (uT ) of brain was acquired to test the performance of the proposed UTE sequence.

Theory And Methods: The rosette trajectory was developed based on rotations of a "petal-like" pattern in the k -k plane, with oscillated extensions in the k -direction for 3D coverage.

Exploration of PDCoV-induced apoptosis through mitochondrial dynamics imbalance and the antagonistic effect of SeNPs.

Porcine Deltacoronavirus (PDCoV), an enveloped positive-strand RNA virus that causes respiratory and gastrointestinal diseases, is widely spread worldwide, but there is no effective drug or vaccine against it. This study investigated the optimal Selenium Nano-Particles (SeNPs) addition concentration (2 - 10 μg/mL) and the mechanism of PDCoV effect on ST (Swine Testis) cell apoptosis, the antagonistic effect of SeNPs on PDCoV. The results indicated that 4 μg/mL SeNPs significantly decreased PDCoV replication on ST cells.

Mechanism of selenomethionine inhibiting of PDCoV replication in LLC-PK1 cells based on STAT3/miR-125b-5p-1/HK2 signaling.

There are no licensed therapeutics or vaccines available against porcine delta coronavirus (PDCoV) to eliminate its potential for congenital disease. In the absence of effective treatments, it has led to significant economic losses in the swine industry worldwide. Similar to the current coronavirus disease 2019 (COVID-19) pandemic, PDCoV is trans-species transmissible and there is still a large desert for scientific exploration.

TRIM67 Deficiency Exacerbates Hypothalamic Inflammation and Fat Accumulation in Obese Mice.

Obesity has achieved the appearance of a global epidemic and is a serious cause for concern. The hypothalamus, as the central regulator of energy homeostasis, plays a critical role in regulating food intake and energy expenditure. In this study, we show that TRIM67 in the hypothalamus was responsive to body-energy homeostasis whilst a deficiency of TRIM67 exacerbated metabolic disorders in high-fat-diet-induced obese mice.

Polyphyllin I Promotes Autophagic Cell Death and Apoptosis of Colon Cancer Cells via the ROS-Inhibited AKT/mTOR Pathway.

Colon cancer is a common malignant tumor of the digestive tract, and it is considered among the biggest killers. Scientific and reasonable treatments can effectively improve the survival rate of patients if performed in the early stages. Polyphyllin I (PPI), a pennogenyl saponin isolated from , has exhibited strong anti-cancer activities in previous studies.

Utilizing novel TBI-on-a-chip device to link physical impacts to neurodegeneration and decipher primary and secondary injury mechanisms.

While clinical observations have confirmed a link between the development of neurodegenerative diseases and traumatic brain injuries (TBI), there are currently no treatments available and the underlying mechanisms remain elusive. In response, we have developed an in vitro pendulum trauma model capable of imparting rapid acceleration injuries to neuronal networks grown on microelectrode arrays within a clinically relevant range of g forces, with real-time electrophysiological and morphological monitoring. By coupling a primary physical insult with the quantification of post-impact levels of known biochemical pathological markers, we demonstrate the capability of our system to delineate and investigate the primary and secondary injury mechanisms leading to post-impact neurodegeneration.

Targeted delivery of acrolein scavenger hydralazine in spinal cord injury using folate-linker-drug conjugation.

Oxidative stress has been shown to play a critical pathogenic role in functional loss after spinal cord injury (SCI). As a direct result of oxidative stress, lipid peroxidation-derived aldehydes have emerged as key culprits that sustain secondary injury and contribute significantly to pathological outcomes. Acrolein, a neurotoxin, has been shown to be elevated in SCI and can result in post-SCI neurological deficits.

Deficiency of autism-related Scn2a gene in mice disrupts sleep patterns and circadian rhythms.

Autism spectrum disorder (ASD) affects ~2% of the population in the US, and monogenic forms of ASD often result in the most severe manifestation of the disorder. Recently, SCN2A has emerged as a leading gene associated with ASD, of which abnormal sleep pattern is a common comorbidity. SCN2A encodes the voltage-gated sodium channel Na1.

Critical role of mitochondrial aldehyde dehydrogenase 2 in acrolein sequestering in rat spinal cord injury.

Lipid peroxidation-derived aldehydes, such as acrolein, the most reactive aldehyde, have emerged as key culprits in sustaining post-spinal cord injury (SCI) secondary pathologies leading to functional loss. Strong evidence suggests that mitochondrial aldehyde dehydrogenase-2 (ALDH2), a key oxidoreductase and powerful endogenous anti-aldehyde machinery, is likely important for protecting neurons from aldehydes-mediated degeneration. Using a rat model of spinal cord contusion injury and recently discovered ALDH2 activator (Alda-1), we planned to validate the aldehyde-clearing and neuroprotective role of ALDH2.

Neuroprotective mechanisms of red clover and soy isoflavones in Parkinson's disease models.

Parkinson's disease (PD) is a neurodegenerative disorder characterized by nigrostriatal degeneration and the spreading of aggregated forms of the presynaptic protein α-synuclein (aSyn) throughout the brain. PD patients are currently only treated with symptomatic therapies, and strategies to slow or stop the progressive neurodegeneration underlying the disease's motor and cognitive symptoms are greatly needed. The time between the first neurobiochemical alterations and the initial presentation of symptoms is thought to span several years, and early neuroprotective dietary interventions could delay the disease onset or slow PD progression.

Evidence of acrolein in synovial fluid of dogs with osteoarthritis as a potential inflammatory biomarker.

Background: Acrolein is a known pro-inflammatory toxic aldehyde, propagating cellular damage and tissue inflammation in humans and animal models of various diseases. Osteoarthritis (OA) has a significant inflammatory component; however, presence of acrolein in synovial fluid of joints with OA has not been previously reported. The first aim of this study was to evaluate evidence of acrolein in the synovial fluid of dogs with OA as well as in Control joints.

Longitudinal auditory pathophysiology following mild blast-induced trauma.

Blast-induced hearing difficulties affect thousands of veterans and civilians. The long-term impact of even a mild blast exposure on the central auditory system is hypothesized to contribute to lasting behavioral complaints associated with mild blast traumatic brain injury (bTBI). Although recovery from mild blast has been studied separately over brief or long time windows, few, if any, studies have investigated recovery longitudinally over short-term and longer-term (months) time windows.