CopperKettle

Интересно, нужно будет почитать, сейчас нет времени:

Pharmacogenomic screening identifies and repurposes leucovorin and dyclonine as pro-oligodendrogenic compounds in brain repair (Jean-Baptiste Huré et al., 2024, in Nature Communications).

Dyclonine (диклонин) - Википедия

Цитата из аннотации:

 In a neonatal chronic hypoxia mouse model mimicking PBI, both compounds promote neural progenitor cell proliferation and oligodendroglial fate acquisition, with leucovorin further enhancing differentiation. In an adult MS model of focal de/remyelination, they improve lesion repair by promoting OPC differentiation while preserving the OPC pool. Additionally, they shift microglia from a pro-inflammatory to a pro-regenerative profile and enhance myelin debris clearance. These findings support the repurposing of leucovorin and dyclonine for clinical trials targeting myelin disorders, offering potential therapeutic avenues for PBI and MS.

Забей, ничего ты не докажешь. Только хуже себе сделаешь (допишут ещё сверху патологий - воспримут твоё возмущение как часть болезни). Не это, так найдут к чему другому прикопаться. В пациентах (к слову для них это не равно человек, личность) они видят прежде всего патологии, ну и некоторых зверушек ниже себя по статусу, за которыми можно наблюдать и угорать втихаря.

Будешь весть себя грустно - поставят депрессию, будешь улыбаться - поставят гипоманию, а может и голоса в голове, будешь вести себя ровно - поставят апатию. Начнёшь писать дневник - поставят склонность к графомании итп...

Будешь с кем то общаться из больных, увидят вероятность такого же диагноза, не будешь - увидят вероятность аутичности

 

Воспринимай понятие нормы прежде всего как статистическое. Нет никакой нормы. Здоров тот кто не спалился

"Норма" - это "так как у всех"

Там в ПНД разные люди, как в жизни. Я недавно ходил к психологу, она вполне нормально общалась. 

У неё был уставший вид.. 

Интересное из новостей. Пока на уровне мышей. 

How the keto diet could one day treat autoimmune disorders by increasing anti-inflammatory compounds - Medical Xpress 

Working with a mouse model of MS, the researchers found that mice who produced more of a particular ketone body, called β-hydroxybutyrate (βHB), had less severe disease.

The additional βHB also prompted the gut bacterium Lactobacillus murinus to produce a metabolite called indole lactic acid (ILA). This blocked the activation of T helper 17 immune cells, which are involved in MS and other autoimmune disorders.

"What was really exciting was finding that we could protect these mice from inflammatory disease just by putting them on a diet that we supplemented with these compounds," said Peter Turnbaugh, Ph.D., of the Benioff Center for Microbiome Medicine.

Свежий обзор в открытом доступе в журнале Metabolic Health and Disease:

Ketone body metabolism and cardiometabolic implications for cognitive health (Kyle Fulghum et al., 2024) 

Докторская диссертация на немецком языке, посвященная влиянию гена CIC (капикуа) на транспорт фолата (сентябрь 2024 года). Мутации CIC были отмечены у детей с расстройством психического развития, а потом были описаны случаи церебральной фолатной недостаточности у детей с мутациями CIC. Автор диссертации попытался исследовать, как ген CIC влияет на экспрессию генов, отвечающих за перенос фолата.  

Der Einfluss genetischer Mutationen im CIC-Gen auf den Folattransport (Leonie Linnea Elisabeth Herholz) (PDF)

Аннотация на английском:

In this dissertation, we studied the influence of the capicua protein on the expression of proteins that are involved in transcellular folate transport. To this end, various expressions of the capicua gene were studied: two missense mutations, one nonsense mutation, and the wildtype of the capicua gene were expressed in different cell lines, and the effect on the expression of further genes was compared. The three mutations were detected in patients with cerebral folate deficiency. This disease is characterized by a low concentration of 5-MTHF in the cerebrospinal fluid, concurrent with a normal hematogenous 5-MTHF level. The disease first manifests clinically in early infancy and may lead to progressive psychomotor retardation, movement disorders like ataxia, and epilepsy when untreated. MRI showed cerebellar and cerebral atrophy and focal demyelination in the white matter. Folate substitution is an effective therapy when started early. The above-mentioned patients did not show mutations in the genes classically associated with folate transport across the blood-brain barrier. However, genome sequencing revealed mutations in the CIC gene. The genes of the folate transport proteins FRα, RFC1, and PCFT all have a binding site for CIC in their regulatory regions. For this reason, a CIC mutation can cause a cerebral folate deficiency. The nonsense mutation p.R353X and the two missense mutations p.G580C and p.T990I were analyzed. Using lentiviral transduction, the mutations were transferred into HeLa cells. To characterize the mutations, immunofluorescences, western blot analyses, q-RT-PCR, and radioactive binding assays were performed. Thereby it was possible to investigate the influence of CIC and the CIC mutations on the localization of CIC, the expression of CIC and the folate transport proteins FRα, RFC1, and PCFT, as well as on the folate binding capacity of the cells. In the wild-type CIC, an upregulation of the expression of FRα was shown. The missense mutations led to a reduced transcription of the FOLR1 gene, but the expression of the FRα protein was equally high as in the wild-type CIC. While this suggests a low-grade functional limitation to the expression of FRα, which could only partially be detected with the present methodology. The nonsense mutation led to the expression of a truncated CIC protein. Due to the loss of the nuclear localization sequence, the truncated CIC protein accumulated ubiquitarily in the cell. In contrast, CIC was detected exclusively in the nucleus in all other cell lines. The expression of FRα was significantly reduced in the cells of the nonsense mutation. The nonsense mutation likely leads to a loss of function of the CIC protein. Further, the truncated protein seems to have a negative effect on the endogenous CIC, as the expression of FRα and the folate binding capacity were even lower than in empty vector-transfected cells. The results of the qRT-PCR and the binding assays were consistent with this finding. Similar results were obtained using a different vector and using a different cell line (Caco-2 cells). We did not detect any effects on the other folate transport proteins, RFC1 and PCFT. Thus, CIC seems to activate the expression of FRα but not of RFC1 or PCFT. Further studies should analyze the molecular mechanisms behind the influence of CIC on folate transport. As CIC has been shown to suppress transcription variously, further proteins could feasibly be involved in the activating function of CIC. A better understanding of the causes of the disease should ultimately enable easier identification of affected patients and allow for the initiation of early and individualized therapy.