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The dopamine stabilizer (-)-OSU6162 attenuates levodopa-induced dyskinesia in the unilateral 6-hydroxydopamine rat model of Parkinson's disease

3 months 3 weeks ago
Levodopa-induced dyskinesia (LID) is a complication that occurs in many patients with Parkinson's disease. (-)-OSU6162 is a clinically tolerable dopamine stabilizer with affinity for both dopaminergic D(2) receptors and serotonergic 5-HT(2A) receptors which has been shown to counteract LID in non-human primates. To investigate whether (-)-OSU6162 can dampen levodopa-induced abnormal involuntary movements in the unilateral 6-OHDA rat model of Parkinson's disease without impairing levodopa-induced...
Daniela Atanasovski

MicroRNAs in neuroplasticity: a comprehensive review of mechanisms and therapeutic strategies for neurodegenerative diseases

3 months 3 weeks ago
MicroRNAs (miRNAs) have emerged as key regulators of neuroplasticity, influencing essential processes such as neurogenesis, synaptogenesis, and neuroinflammatory responses. This review provides a comprehensive overview of the general roles of miRNAs in neuroplasticity and synthesizes recent insights from both preclinical and clinical studies, including transcriptomic analyses and miRNA profiling, to elucidate the molecular mechanisms by which these miRNAs modulate neuronal function. We have...
Pedro César de Souza

Nucleoside reverse transcriptase inhibitors as a therapeutic opportunity to counteract inflammaging and age-related diseases: New evidence from epidemiological data

3 months 3 weeks ago
Nucleoside Reverse Transcriptase Inhibitors (NRTIs), widely used to treat HIV and hepatitis B, have recently been shown to possess anti-inflammatory properties by inhibiting inflammasome activation. Epidemiological studies have revealed a significantly reduced incidence of age-related diseases, such as Alzheimer's disease (AD) and type 2 diabetes mellitus (T2DM), among patients chronically treated with NRTIs, but not with other classes of antiretroviral drugs. In this short review, we explore...
Fabiola Olivieri

Interplay of genetic predisposition, plasma metabolome and Mediterranean diet in dementia risk and cognitive function

3 months 3 weeks ago
Alzheimer's disease (AD) and AD-related dementias (AD/ADRD) have a substantial genetic basis, with APOE4 homozygotes increasingly recognized as a distinct genetic subtype. To identify genotype-specific metabolic pathways and modifiable risk factors, we integrated genetic, plasma metabolomic and dietary data from 4,215 women and 1,490 men in prospective cohorts. Here we show that the associations of 57 metabolites with dementia risk varied by APOE4 genotype or other AD/ADRD risk variants. For...
Yuxi Liu

Chronic inflammation and cognitive frailty in older adults: A narrative review

3 months 3 weeks ago
Cognitive Frailty (CF) is a clinical syndrome characterized by the co-occurrence of physical frailty and cognitive impairment in the absence of dementia. This geriatric condition has emerged as a significant contributor to compromised health status and diminished quality of life among aging populations, yet its underlying pathological mechanisms remain incompletely elucidated. Chronic low-grade inflammation, recognized as a hallmark of biological aging, has been implicated in the pathogenesis of...
Qiqi Jiang

Effects of Music Imaging on Older Adults With Mild Cognitive Impairment: A Randomized Controlled Trial

3 months 3 weeks ago
CONCLUSIONS AND IMPLICATIONS: This study revealed the beneficial effects of music imaging on cognitive function, neuropsychiatric symptoms, sleep quality, and quality of life among older adults with MCI. These findings support the application of music imaging among older adults with MCI with the aim of slowing cognitive decline, improving symptoms, and promoting healthy aging. [The study was registered with the China Clinical Trial Registry (ChiCTR2400081469) and approved by the Ethics Committee...
Meng Zhou

High content-imaging drug synergy screening identifies specific senescence-related vulnerabilities of mesenchymal neuroblastomas

3 months 3 weeks ago
Neuroblastomas encompass malignant cells with varying degrees of differentiation, ranging from adrenergic (adr) cells resembling the sympathoadrenal lineage to undifferentiated, stem-cell-like mesenchymal (mes) cancer cells. Relapsed neuroblastomas, which often have mesenchymal features, have a poor prognosis and respond less to anticancer therapies, necessitating the development of novel treatment strategies. To identify novel treatment options, we analyzed the sensitivity of 91 pediatric cell...
Sonja Herter

Ankyrin-B modulates mitochondrial fission in skeletal muscle and is required for optimal endurance exercise capacity

3 months 3 weeks ago
Mitochondrial dynamics enable cellular adaptation to fluctuations in energy demand, such as those imposed on skeletal muscle by exercise, metabolic disorders, or aging. Here, we report a novel pathway that modulates mitochondria dynamics in skeletal muscle involving the scaffolding protein ankyrin-B. Rare variants in ankyrin-B, encoded by ANK2, increase risk for cardio-metabolic syndrome in humans and mice. We show that mice selectively lacking skeletal muscle ankyrin-B have reduced endurance...
Kayleigh M Voos

Microbiota-derived corisin accelerates kidney fibrosis by promoting cellular aging

3 months 3 weeks ago
The increasing global prevalence of diabetic nephropathy poses substantial health and economic burdens. Currently, effective anti-fibrotic therapies for managing kidney fibrosis associated with chronic kidney disease are lacking. This study reveals corisin, a microbiota-derived peptide, as a central driver in the progression of diabetic kidney fibrosis. Corisin levels were found to be markedly elevated in the serum of diabetic chronic kidney disease patients relative to healthy controls, with...
Taro Yasuma

Immunotherapy and senolytics in head and neck squamous cell carcinoma: phase 2 trial results

3 months 3 weeks ago
Recent advancements in cancer immunotherapy have improved patient outcomes, yet responses to immunotherapy remain moderate. Immunosenescence has been shown to contribute to the development and progression of various diseases; however, its specific role in solid tumors has not been fully delineated. Here we conducted a phase 2 clinical trial involving 51 patients with cancer undergoing neoadjuvant chemoimmunotherapy and applied single-cell RNA as well as TCR and BCR sequencing on tumor and blood...
Niu Liu