A Novel Gliotransmitter, L-β-Aminoisobutyric Acid, Contributes to Pathophysiology of Clinical Efficacies and Adverse Reactions of Clozapine DOI Creative Commons
Kouji Fukuyama, Eishi Motomura, Motohiro Okada

и другие.

Biomolecules, Год журнала: 2023, Номер 13(9), С. 1288 - 1288

Опубликована: Авг. 23, 2023

Clozapine is listed as one of the most effective antipsychotics and has been approved for treating treatment-resistant schizophrenia (TRS); however, several type A B adverse reactions, including weight gain, metabolic complications, cardiotoxicity, convulsions, discontinuation syndromes, exist. The critical mechanisms clinical efficacy schizophrenia, TRS, reactions clozapine have not elucidated. Recently, GABA isomer L-β-aminoisobutyric acid (L-BAIBA), a protective myokine in peripheral organs, was identified candidate novel transmission modulator central nervous system (CNS). L-BAIBA activates adenosine monophosphate-activated protein kinase (AMPK) signalling both organs CNS. Activated AMPK an established major target insulin-resistant diabetes, whereas activated hypothalamus contributes to pathophysiology gain disturbances. increases synthesis hypothalamus. In addition, various functions CNS recently elucidated, activator GABA-B group-III metabotropic glutamate (III-mGlu) receptors. Considering expressions III-mGlu receptors (localised presynaptic regions), activation can explain distinct therapeutic advantages or TRS associated with N-methyl-D-aspartate (NMDA) receptor disturbance compared other atypical via inhibition persistent tonic hyperactivation thalamocortical glutamatergic prefrontal cortex. also gliotransmitter, detailed exploration function tripartite synaptic further elucidate effectiveness and/or specific clozapine.

Язык: Английский

An insight into brown/beige adipose tissue whitening, a metabolic complication of obesity with the multifactorial origin DOI Creative Commons
Khanyisani Ziqubu, Phiwayinkosi V. Dludla, Sinenhlanhla X. H. Mthembu

и другие.

Frontiers in Endocrinology, Год журнала: 2023, Номер 14

Опубликована: Фев. 16, 2023

Brown adipose tissue (BAT), a thermoregulatory organ known to promote energy expenditure, has been extensively studied as potential avenue combat obesity. Although BAT is the opposite of white (WAT) which responsible for storage, shares thermogenic capacity with beige that emerges from WAT depots. This unsurprising both and display huge difference in terms their secretory profile physiological role. In obesity, content declines these tissues acquire characteristics via process called “whitening”. rarely explored its implication whether it contributes or exacerbates Emerging research demonstrated BAT/beige whitening sophisticated metabolic complication obesity linked multiple factors. The current review provides clarification on influence various factors such diet, age, genetics, thermoneutrality, chemical exposure whitening. Moreover, defects mechanisms underpin are described. Notably, can be marked by accumulation large unilocular lipid droplets, mitochondrial degeneration, collapsed capacity, virtue dysfunction, devascularization, autophagy, inflammation.

Язык: Английский

Процитировано

47
Neurobiological mechanisms of nicotine's effects on feeding and body weight DOI
Y. Li, Jian Mao,

Guobi Chai

и другие.

Neuroscience & Biobehavioral Reviews, Год журнала: 2025, Номер 169, С. 106021 - 106021

Опубликована: Янв. 16, 2025

Язык: Английский

Процитировано

1
Therapeutic Potential and Limitation of Serotonin Type 7 Receptor Modulation DOI Open Access
Kouji Fukuyama, Eishi Motomura, Motohiro Okada

и другие.

International Journal of Molecular Sciences, Год журнала: 2023, Номер 24(3), С. 2070 - 2070

Опубликована: Янв. 20, 2023

Although a number of mood-stabilising atypical antipsychotics and antidepressants modulate serotonin type 7 receptor (5-HT7), the detailed contributions 5-HT7 function to clinical efficacy pathophysiology have not been fully understood. The antipsychotic agent, lurasidone, partial agonist reuptake inhibitor, vortioxetine, exhibit higher binding affinity than other conventional antidepressants. To date, initially expected rapid onset antidepressant effects-in comparison with or antipsychotics-due inhibition has observed lurasidone vortioxetine; however, several studies suggest that likely contributes quality life patients schizophrenia mood disorders via improvement cognition. Furthermore, recent preclinical reported might mitigate antipsychotic-induced weight gain metabolic complication by blocking monoamine receptors. Further for development modulation against neurodevelopmental neurodegenerative diseases ongoing. various findings from indicate possibility modifications can provide two independent strategies. first is ameliorates dysfunction inter-neuronal transmission in mature networks. activation improve due microstructure abnormality neurotransmission network-which could be unaffected therapeutic agents-via modulating intracellular signalling during stage loss neural networks aging. This review attempts describe current novel applications based on findings.

Язык: Английский

Процитировано

15
Olanzapine, risperidone and ziprasidone differently affect lysosomal function and autophagy, reflecting their different metabolic risk in patients DOI Creative Commons
Marco Pozzi, Chiara Vantaggiato, F Brivio

и другие.

Translational Psychiatry, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 8, 2024

Abstract The metabolic effects induced by antipsychotics in vitro depend on their action the trafficking and biosynthesis of sterols lipids. Previous research showed that with different adverse patients cause similar alterations vitro, suggesting low clinical usefulness cellular studies. Moreover, inhibition peripheral AMPK was suggested as potential aetiopathogenic mechanisms olanzapine, autophagy were reported for several antipsychotics. We thus assessed, clinically-relevant culture conditions, risperidone ziprasidone, respectively high, medium, risk patients, finding relevant differences among them. highlighted that: olanzapine impairs lysosomal function affecting autophagosome clearance, increasing intracellular lipids sterols; ziprasidone activates autophagic flux reducing lipids; increases lipid accumulation, while it does not affect function. These align impact patients. also provided evidence metformin add-on improved olanzapine-treated cells reduced accumulation both an AMPK-dependent way; increased production bile acids to eliminate cholesterol accumulations caused olanzapine. results have implications. demonstrated impacts actually action, supporting possibility a personalised antipsychotic treatment. we found can fully revert phenotype but one still SREBP2.

Язык: Английский

Процитировано

5
Benefits of Monascus anka solid-state fermentation for quinoa polyphenol bioaccessibility and the anti-obesity effect linked with gut microbiota DOI
Kai Huang, Guoqiang Chu,

Pei Yang

и другие.

Food & Function, Год журнала: 2024, Номер 15(4), С. 2208 - 2220

Опубликована: Янв. 1, 2024

In our previous study, a polyphenol-utilization targeted quinoa product was developed via solid-state fermentation with Monascus anka .

Язык: Английский

Процитировано

5
Extracellular vesicles in cancer cachexia: deciphering pathogenic roles and exploring therapeutic horizons DOI Creative Commons
Yifeng Wang, Shengguang Ding

Journal of Translational Medicine, Год журнала: 2024, Номер 22(1)

Опубликована: Май 27, 2024

Abstract Cancer cachexia (CC) is a debilitating syndrome that affects 50–80% of cancer patients, varying in incidence by type and significantly diminishing their quality life. This multifactorial characterized muscle fat loss, systemic inflammation, metabolic imbalance. Extracellular vesicles (EVs), including exosomes microvesicles, play crucial role the progression CC. These vesicles, produced cells others within tumor environment, facilitate intercellular communication transferring proteins, lipids, nucleic acids. A comprehensive review literature from databases such as PubMed, Scopus, Web Science reveals insights into formation, release, uptake EVs CC, underscoring potential diagnostic prognostic biomarkers. The also explores therapeutic strategies targeting EVs, which include modifying release content, utilizing them for drug delivery, genetically altering contents, inhibiting key pathways. Understanding CC opens new avenues approaches, potentially mitigating syndrome’s impact on patient survival

Язык: Английский

Процитировано

5
Neuroprotective effect of small extracellular vesicle-mediated targeting of AMPKα2 in cerebral ischemia DOI Creative Commons
Alberto Ouro,

Amanda Rodríguez-Díaz,

Tania López-González

и другие.

Metabolism, Год журнала: 2025, Номер unknown, С. 156160 - 156160

Опубликована: Фев. 1, 2025

Язык: Английский

Процитировано

0
Lower SLC7A2 expression is associated with enhanced multidrug resistance, less immune infiltrates and worse prognosis of NSCLC DOI Creative Commons
Shanshan Jiang, Junrong Zou, Jianyu Dong

и другие.

Cell Communication and Signaling, Год журнала: 2023, Номер 21(1)

Опубликована: Янв. 13, 2023

Abstract Background Solute carrier family 7 member 2 (SLC7A2), a cationic amino acid transporter, is lowly expressed in ovarian and hepatocellular cancers, which associated with their worse prognosis. However, its roles the prognosis, drug resistance immune infiltration non-small-cell lung cancer (NSCLC) are unclear. Methods We chose SLC7A2 from RNA-Seq of paclitaxel/cisplatin-resistant A549 cells, then bioinformatics, cell lines construction, RT-qPCR, CCK8 were performed to investigate role. Result analyzed 223 differentially genes (DEGs) cells found that expression was down-regulated NSCLC. Lower recurrence-free survival (RFS) silencing enhanced proliferation NSCLC insensitivity paclitaxel, cisplatin, gemcitabine vitro. Activation AMPK has up-regulated sensitivity anti-tumor drugs, could be attributed E2F1’s regulation. In addition, levels correlated numbers infiltrated neutrophils, macrophages, dendritic marker genes, like CD86, HLA-DPA1 ITGAM. Conclusions may act as tumor suppressor modulate sensitivity,

Язык: Английский

Процитировано

11
Astrocytic insulin receptor controls circadian behavior via dopamine signaling in a sexually dimorphic manner DOI Creative Commons

Antía González-Vila,

María Luengo-Mateos,

María Silveira-Loureiro

и другие.

Nature Communications, Год журнала: 2023, Номер 14(1)

Опубликована: Дек. 9, 2023

Mammalian circadian clocks respond to feeding and light cues, adjusting internal rhythms with day/night cycles. Astrocytes serve as timekeepers, driving daily physiological rhythms; however, it's unknown how they ensure precise cycle-to-cycle rhythmicity. This is critical for understanding why mistimed or erratic feeding, in shift work, disrupts physiology- a condition linked type 2 diabetes obesity. Here, we show that astrocytic insulin signaling sets the free-running period of locomotor activity female mice food entrainment male mice. Additionally, ablating receptor hypothalamic astrocytes alters cyclic energy homeostasis differently Remarkably, mutants exhibit altered dopamine metabolism, pharmacological modulation dopaminergic partially restores distinct traits both mutant Our findings highlight role insulin-dopaminergic conveying time-of-feeding lighting cues astrocyte clock, thus governing behavior sex-specific manner.

Язык: Английский

Процитировано

11
FAcTs on fire: Exploring thermogenesis DOI

Amanda Rodríguez-Díaz,

Carlos Diéguez, Miguel López

и другие.

Advances in genetics, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

Процитировано

0