The transcriptional regulatory machinery in mitochondrial bioenergetics is complex and is still not completely understood. We previously demonstrated that the histone methyltransferase Smyd1 regulates mitochondrial energetics. Here, we identified Perm1 (PPARGC-1 and ESRR-induced regulator, muscle specific 1) as a downstream target of Smyd1 through RNA-seq. Chromatin immunoprecipitation assay showed that Smyd1 directly interacts with the promoter of Perm1 in the mouse heart, and this interaction was significantly reduced in mouse hearts failing due to pressure overload for 4 weeks, where Perm1 was downregulated (24.4 ± 5.9% of sham, p<0.05). Similarly, the Perm1 protein level was significantly decreased in patients with advanced heart failure (55.2 ± 13.1% of donors, p<0.05). Phenylephrine (PE)-induced hypertrophic stress in cardiomyocytes also led to downregulation of Perm1 (55.7 ± 5.7% of control, p<0.05), and adenovirus-mediated overexpression of Perm1 rescued PE-induced downregulation of estrogen-related receptor alpha (ERRα), a key transcriptional regulator of mitochondrial energetics, and its target gene, Ndufv1 (Complex I). Pathway enrichment analysis of cardiomyocytes in which Perm1 was knocked-down by siRNA (siPerm1), revealed that the most downregulated pathway was metabolism. Cell stress tests using the Seahorse XF analyzer showed that basal respiration and ATP production were significantly reduced in siPerm1 cardiomyocytes (40.7% and 23.6% of scrambled-siRNA, respectively, both p<0.05). Luciferase reporter gene assay further revealed that Perm1 dose-dependently increased the promoter activity of the ERRα gene and known

Regulation of mitochondrial energetics is key to maintain cardiac function. Perm1 ( P GC-1 and E RR- r egulator, m uscle 1 ) was previously shown to enhance exercise endurance in skeletal muscle through increasing mitochondrial bioenergetics. Despite the significant expression levels of Perm1 in the heart, its role in the healthy and diseased hearts has never been investigated. We found that cardiac Perm1 was downregulated in the mouse failing heart subjected to pressure overload for 4 weeks (24.4 ± 5.9 % of sham operated, p<0.05) and in patients with advanced heart failure (55.2 ± 13.1 % of donors, p<0.05) suggesting a role of Perm1 in cardiac pathology. Phenylephrine (PE)-induced hypertrophy in cardiomyocytes was accompanied by downregulation of Perm1 (55.7 ± 5.7 % of control, p <0.05), and adenovirus-mediated overexpression of Perm1 rescued PE-induced downregulation of estrogen-related receptor alpha (ERRα), a key transcriptional regulator of mitochondrial energetics, and its target gene, Ndufv1 (Complex I), suggesting that downregulation of Perm1 contributes to the development of mitochondrial dysfunction in response to hypertrophic stimuli. Pathway enrichment analysis in cardiomyocytes where Perm1 was knocked-down by siRNA (siPerm1) revealed that the most downregulated pathway was metabolism, while upregulated pathways were mostly related to synthesis and assembly of collagen fibrils (i.e. Col3a1, Col5a1, Col11a1, Lox). Cell stress test using Seahorse XF analyzer showed that basal respiration and ATP production were significantly reduced in siPerm1 cardiomyocytes (40.7 % and 23.6 % of scrambled-siRNA, respectively, both p <0.05). Luciferase reporter gene assay further revealed that Perm1 dose-dependently increased the promoter activity of the ERRα gene and known targets of ERRα, Ndufv1 and Ndufs1 (Complex I). Furthermore, systemic Perm1-knockout mice developed heart failure (3 months old ejection fraction 38.8 %), concurrent with downregulation of proteins involved in oxidative phosphorylation, such as Ndufaf4 and Uqcr11 (-6.14 and -2.39 in fold change, respectively), and increased fibrosis. These results suggest that Perm1 is a novel regulator of cardiac metabolism and function, that enhances energetics and suppresses fibrosis.

Обзор литературы посвящен распространенной функционирующей нейроэндокринной опухоли β-клеток островков Лангерганса поджелудочной железы, которая характеризуется неконтролируемой продукцией инсулина. Патофизиологические основы клинических проявлений опухолей из β-клеток островков Лангерганса обусловлены гормональной активностью этих новообразований. При отсутствии подчинения физиологическим механизмам, регулирующим гомеостаз уровня глюкозы, β-клеточные аденомы приводят к развитию состояния хронической гипогликемии. В связи с тем, что симптоматология инсулиномы возникает вследствие гиперинсулинемии и гипогликемии, выраженность клинических проявлений заболевания в каждом отдельном случае свидетельствует об индивидуальной чувствительности больного к инсулину и недостатку сахара крови. Подавляющее большинство инсулинопродуцирующих опухолей поджелудочной железы имеет размер, не превышающий 0,5–2 см в диаметре, что создает трудности их обнаружения во время операции. Так, у 20 % больных при первой, а иногда и при второй и третьей операциях не удается выявить опухоль. Злокачественные инсулиномы встречаются в 10–15 % случаев, причем треть из них метастазируют. Единственным радикальным методом лечения инсулиномы остается оперативное вмешательство. Консервативные методы лечения применяются только у неоперабельных больных, а также как средства, временно устраняющие гипогликемию, и используются для подготовки больного к оперативному лечению. Подчеркивается, что для успешного лечения больных с эндогенным гиперинсулинизмом необходим комплексный командный подход, включающий применение современных методов визуализации и использование высокотехнологичных способов лечения.

Kidney tuberculosis in humans is quite frequent. For example, in the Men's Urology Department of the Obukhov Hospital (Leningrad), 153 cases of this disease have been observed over the past 14 years. According to the statistics of different authors, it can be seen that 2-3 per 100 examined cadavers could find tbc renia, and per 100 examined cadavers of phthisis, from 8 to 30 represented tbc changes of the kidneys as well. Fedorov counts 19% tbc among other surgical kidney diseases. During the first year of the existence of the Urological Department of the 3rd Soviet People's Hospital in Odessa I managed to observe only 3 cases of renal tbc, which, in relation to the total number of patients in the department (534 people), is 0.56%, and in relation to the total number of urological patients in the hospital in 1923-24 (218 people) - 1.5%. (218 people) - 1.37.

The question of the nutrition of patients has recently occupied a prominent place in the German medical literature, as well as in Berlin clinics. Nutrition for infants, nutrition for patients obsessed with diseases of the gastrointestinal tract, nutrition for those suffering from metabolic disorders, nutrition for surgical patients, pre- and postoperative - cause a lot of controversy in medical circles and more and more attracts the attention of practitioners.