From Collagen Mimetics to Collagen Hybridization and Back.

ConspectusFacilitated by the unique triple-helical protein structure, fibrous collagens, the principal proteins in animals, demonstrate a dual function of serving as building blocks for tissue scaffolds and as a bioactive material capable of swift renewal in response to environmental changes. While studies of triple-helical collagen mimetic peptides (CMPs) have been instrumental in understanding the molecular forces responsible for the folding and assembly of triple helices, as well as identifying bioactive regions of fibrous collagen molecules, single-strand CMPs that can specifically target and hybridize to denatured collagens (i.e., collagen hybridizing peptides, CHPs) have proven useful in identifying the remodeling activity of collagen-rich tissues related to development, homeostasis, and pathology. Efforts to improve the utility of CHPs have resulted in the development of new skeletal structures, such as dimeric and cyclic CHPs, as well as the incorporation of artificial amino acids, including fluorinated proline and N-substituted glycines (peptoid residues). In particular, dimeric CHPs were used to capture collagen fragments from biological fluid for biomarker study, and the introduction of peptoid-based collagen mimetics has sparked renewed interest in peptidomimetic research because peptoids enable a stable triple-helical structure and the presentation of an extensive array of side chain structures offering a versatile platform for the development of new collagen mimetics.This Account will cover the evolution of our research from CMPs as biomaterials to ongoing efforts in developing triple-helical peptides with practical theranostic potential in targeting denatured and damaged collagens. Our early efforts in functionalizing natural collagen scaffolds via noncovalent modifications led to the discovery of an entirely new use of CMPs. This discovery resulted in the development of CHPs that are now used by many different laboratories for the investigation of pathologies associated with changes in the structures of extracellular matrices including fibrosis, cancer, and mechanical damage to collagen-rich, load-bearing tissues. Here, we delve into the essential design features of CHPs contributing to their collagen binding properties and practical usage and explore the necessity for further mechanistic understanding of not only the binding processes (e.g., binding domain and stoichiometry of the hybridized complex) but also the biology of collagen degradation, from proteolytic digestion of fibrils to cellular processing of collagen fragments. We also discuss the strengths and weaknesses of peptoid-based triple-helical peptides as applied to collagen hybridization touching on thermodynamic and kinetic aspects of triple-helical folding. Finally, we highlight current limitations and future directions in the use of peptoid building blocks to develop bioactive collagen mimetics as new functional biomaterials.

TOTEM: a multi-cancer detection and localization approach using circulating tumor DNA methylation markers.

BACKGROUND: Detection of cancer and identification of tumor origin at an early stage improve the survival and prognosis of patients. Herein, we proposed a plasma cfDNA-based approach called TOTEM to detect and trace the cancer signal origin (CSO) through methylation markers. METHODS: We performed enzymatic conversion-based targeted methylation sequencing on plasma cfDNA samples collected from a clinical cohort of 500 healthy controls and 733 cancer patients with seven types of cancer (breast, colorectum, esophagus, stomach, liver, lung, and pancreas) and randomly divided these samples into a training cohort and a testing cohort. An independent validation cohort of 143 healthy controls, 79 liver cancer patients and 100 stomach cancer patients were recruited to validate the generalizability of our approach. RESULTS: A total of 57 multi-cancer diagnostic markers and 873 CSO markers were selected for model development. The binary diagnostic model achieved an area under the curve (AUC) of 0.907, 0.908 and 0.868 in the training, testing and independent validation cohorts, respectively. With a training specificity of 98%, the specificities in the testing and independent validation cohorts were 100% and 98.6%, respectively. Overall sensitivity across all cancer stages was 65.5%, 67.3% and 55.9% in the training, testing and independent validation cohorts, respectively. Early-stage (I and II) sensitivity was 50.3% and 45.7% in the training and testing cohorts, respectively. For cancer patients correctly identified by the binary classifier, the top 1 and top 2 CSO accuracies were 77.7% and 86.5% in the testing cohort (n = 148) and 76.0% and 84.0% in the independent validation cohort (n = 100). Notably, performance was maintained with only 21 diagnostic and 214 CSO markers, achieving a training AUC of 0.865, a testing AUC of 0.866, and an integrated top 2 accuracy of 83.1% in the testing cohort. CONCLUSIONS: TOTEM demonstrates promising potential for accurate multi-cancer detection and localization by profiling plasma methylation markers. The real-world clinical performance of our approach needs to be investigated in a much larger prospective cohort.

Changes in nutritional status and the development of obesity and metabolic syndrome following pediatric heart transplantation.

BACKGROUND: Nutritional status in pediatric patients undergoing heart transplantation (HT) is frequently a focus of clinical management and requires high resource utilization. Pre-operative nutrition status has been shown to affect post-operative mortality but no studies have been performed to assess how nutritional status may change and the risk of developing nutritional comorbidities long-term in the post-transplant period. METHODS: A single-center retrospective chart review of patients ≥2 years of age who underwent heart transplantation between 1/1/2005 and 4/30/2020 was performed. Patient data were collected at listing, time of transplant, 1-year, and 3-year follow-up post-transplant. Nutrition status was classified based on body mass index (BMI) percentile in the primary analysis. Alternative nutritional indices, namely the nutrition risk index (NRI), prognostic nutrition index (PNI), and BMI z-score, were utilized in secondary analyses. RESULTS: Of the 63 patients included, the proportion of patients with overweight/obese status increased from 21% at listing to 41% at 3-year follow-up. No underweight patients at listing became overweight/obese at follow-up. Of patients who were overweight/obese at listing, 88% maintained that status at 3-year follow-up. Overweight/obese status at listing, 1-year, and 3-year post-transplantation were significantly associated with developing metabolic syndrome. In comparison to the alternative nutritional indices, BMI percentile best predicted post-transplant metabolic syndrome. CONCLUSIONS: The results suggest that pediatric patients who undergo heart transplantation are at risk of developing overweight/obesity and related nutritional sequelae (ie, metabolic syndrome). Improved surveillance and interventions targeted toward overweight/obese HT patients should be investigated to reduce the burden of associated comorbidities.

Cardiac MRI feature-tracking-derived torsion mechanics in systolic and diastolic dysfunction in systemic light-chain cardiac amyloidosis.

AIM: To describe the myocardial torsion mechanics in cardiac amyloidosis (CA), and evaluate the correlations between left ventricle (LV) torsion mechanics and conventional parameters using cardiac magnetic resonance imaging feature tracking (CMR-FT). MATERIALS AND METHODS: One hundred and thirty-nine patients with light-chain CA (AL-CA) were divided into three groups: group 1 with preserved systolic function (LV ejection fraction [LVEF] ≥50%, n=55), group 2 with mildly reduced systolic function (40% ≤ LVEF <50%, n=51), and group 3 with reduced systolic function (LVEF <40%, n=33), and compared with age- and gender-matched healthy controls (n=26). All patients underwent cine imaging and late gadolinium-enhancement (LGE). Cine images were analysed offline using CMR-FT to estimate torsion parameters. RESULTS: Global torsion, base-mid torsion, and peak diastolic torsion rate (diasTR) were significantly impaired in patients with preserved systolic function (p<0.05 for all), whereas mid-apex torsion and peak systolic torsion rate (sysTR) were preserved (p>0.05 for both) compared with healthy controls. In patients with mildly reduced systolic function, global torsion and base-mid torsion were lower compared to those with preserved systolic function (p<0.05 for both), while mid-apex torsion, sysTR, and diasTR were preserved (p>0.05 for all). In patients with reduced systolic function, only sysTR was significantly worse compared with mildly reduced systolic function (p<0.05). At multivariable analysis, right ventricle (RV) end-systolic volume RVESV index and NYHA class were independently related to global torsion, whereas LVEF was independently related to sysTR. RV ejection fraction (RVEF) was independently related to diasTR. LV global torsion performed well (AUC 0.71; 95% confidence interval [CI]: 0.61, 0.77) in discriminating transmural from non-transmural LGE in AL-CA patients. CONCLUSION: LV torsion mechanics derived by CMR-FT could help to monitor LV systolic and diastolic function in AL-CA patients and function as a new imaging marker for LV dysfunction and LGE transmurality.

Genomic and morphological characterization of a new Thiothrix species from a sulfide hot spring of the Zmeinaya bay (Northern Baikal, Russia).

A survey for bacteria of the genus Thiothrix indicated that they inhabited the area where the water of the Zmeiny geothermal spring (northern basin of Lake Baikal, Russia) mixed with the lake water. In the coastal zone of the lake oxygen (8.25 g/L) and hydrogen sulfide (up to 1 mg/L) were simultaneously present at sites of massive growth of these particular Thiothrix bacteria. Based on the analysis of the morphological characteristics and sequence of individual genes (16S rRNA, rpoB and tilS), we could not attribute the Thiothrix from Lake Baikal to any of the known species of this genus. To determine metabolic capabilities and phylogenetic position of the Thiothrix sp. from Lake Baikal, we analyzed their whole genome. Like all members of this genus, the bacteria from Lake Baikal were capable of organo-heterotrophic, chemolithoheterotrophic, and chemolithoautotrophic growth and differed from its closest relatives in the spectrum of nitrogen and sulfur cycle genes as well as in the indices of average nucleotide identity (ANI < 75-94%), amino acid identity (AAI < 94%) and in silico DNA-DNA hybridization (dDDH < 17-57%), which were below the boundary of interspecies differences, allowing us to identify them as novel candidate species.

Rev-erbα attenuates refractory periapical periodontitis via M1 polarization: An in vitro and in vivo study.

AIM: Rev-erbα has been reported to regulate the healing of inflammatory lesions through its effect on the immune system in a variety of inflammatory disease. Moreover, the balance of macrophages polarization plays a crucial role in immune response and inflammatory progression. However, in refractory periapical periodontitis (RAP), the role of Rev-erbα in inflammatory response and bone resorption by regulating macrophage polarization remains unclarified. The aims of the present study were to investigate the expression of Rev-erbα in experimental RAP and to explore the relationship between Rev-erbα and macrophage polarization through the application of its pharmacological agonist SR9009 into the in vivo and in vitro experiments. METHODOLOGY: Enterococcus faecalis-induced RAP models were established in SD rats. Histological staining and micro-computed tomography scanning were used to evaluate osteoclastogenesis and alveolar bone resorption. The expression of Rev-erbα and macrophage polarization were detected in the periapical tissues from rats by immunofluorescence, flow cytometry, and western blots. Furthermore, immunohistochemical staining and enzyme-linked immunosorbent assay were performed to explore the relationship between Rev-erbα and inflammatory cytokines related to macrophage polarization. RESULT: Compared to healthy periapical tissue, the expression of Rev-erbα was significantly down-regulated in macrophages from inflammatory periapical area, especially in Enterococcus faecalis-induced periapical lesions, with obvious type-1 macrophage (M1)-like dominance and the production of pro-inflammatory cytokines. In addition, Rev-erbα activation by SR9009 could induce type-2 macrophage (M2)-like polarization in periapical tissue and THP1 cell line, followed by increased secretion of anti-inflammatory cytokines IL-10 and TGF-ß. Furthermore, intracanal application of SR9009 reduced the lesion size and promoted the repair of RAP by decreasing the number of osteoclasts and enhancing the formation of mineralized tissue in periapical inflammatory lesions. CONCLUSIONS: Rev-erbα played an essential role in the pathogenesis of RAP through its effect on macrophage polarization. Targeting Rev-erbα might be a promising and prospective therapy method for the prevention and management of RAP.

Novel circular RNA Sestrin1 promotes chicken myoblast proliferation and differentiation via circSesn1/miR-16-5p/SESN1 pathway.

1. The development of chicken skeletal muscle is directly relevant to poultry husbandry production. Numerous studies have suggested that circular RNA play pivotal roles in muscle development. However, the functions and mechanisms of most circRNA in chicken myogenesis remain largely unknown.2. This study identified a novel circSESN1 based on existing sequencing data and examined its authenticity and subcellular localisation by enzyme digestion and RNA fluorescence in situ hybridisation. Additionally, there was a positive correlation between the expression levels of circSESN1 and the developmental stage of chicken muscle.3. Mechanistically, knockdown or overexpression of circSESN1 was performed in primary myoblasts to validate its function. The interactions between circSESN1, miR-16-5p, and the target gene sestrin 1 (SESN1) were investigated using bioinformatics analysis and a dual fluorescein reporter system. Real-time qPCR, a cell proliferation assay, and immunofluorescence staining techniques were used to investigate the promotion effect of circSESN1 on myoblast proliferation and differentiation by miR-16-5p/SESN1 pathway.4. The results demonstrated that the newly identified chicken circSESN1 directly sponges gga-miR-16-5p to regulate SESN1 gene expression, promoting myoblast proliferation and differentiation.

Comprehensive analysis of changes in expression of lncRNA, microRNA and mRNA in liver tissues of chickens with high or low abdominal fat deposition.

1. The liver of chickens is a dominant lipid biosynthetic tissue and plays a vital role in fat deposition, particularly in the abdomen. To determine the molecular mechanisms involved in its lipid metabolism, the livers of chickens with high (H) or low (L) abdominal fat content were sampled and sequencing on long non-coding RNA (lncRNA), messenger RNA (mRNA) and small RNA (microRNA) was performed.2. In total, 351 expressed protein-coding genes for long non-coding RNA (DEL; 201 upregulated and 150 downregulated), 400 differentially expressed genes (DEG; 223 upregulated and 177 downregulated) and 10 differentially expressed miRNA (DEM; four upregulated and six downregulated) were identified between the two groups. Multiple potential signalling pathways related to lipogenesis and lipid metabolism were identified via pathway enrichment analysis. In addition, 173 lncRNA - miRNA - mRNA interaction regulatory networks were identified, including 30 lncRNA, 27 mRNA and seven miRNA.3. These networks may help regulate lipid metabolism and fat deposition. Five promising candidate genes and two lncRNA may play important roles in the regulation of adipogenesis and lipid metabolism in chickens.

[Mid-term efficacy evaluation of ABO incompatible living relative kidney transplantation based on protocol biopsy].

Objective: To evaluate the mid-term efficacy of ABO incompatible living donor kidney transplantation (ABOi-KT) based on the results of routine renal biopsy for transplantation. Methods: Retrospective collection of clinical data from 23 pairs of ABOi-KT donors and recipients at the First Affiliated Hospital of Sun Yat-sen University from July 2015 to November 2021. ABOi-KT was performed on recipients after desensitization treatment, and the results of routine kidney transplant biopsy at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were analyzed. Combined with blood type antibody levels and renal function recovery, the mid-term efficacy of ABOi-KT was evaluated. Results: Among the 23 recipients, there were 19 males and 4 females; age range from 19 to 47 years old [(29.6±6.7) years old], all underwent ABOi-KT successfully after receiving desensitization treatment. The follow-up time was (44.6±22.4) months, of which 22 cases were followed up for more than 1 year. The incidence rates of rejection reactions at 1 week, 1 month, 3 months, 6 months, and 12 months after surgery were 15.0% (3/20), 11.1% (1/9), 7.7% (1/13), 25.0% (3/12), and 12.5% (1/8), respectively. For receptors with rejection reactions, targeted anti-rejection therapy was performed based on clinical symptoms and various indicators. Borderline T cell mediated rejection (TCMR) can be converted to mild tubular inflammation after anti-rejection treatment. The positive rate of complement C4d in peritubular capillaries was 95.0% (19/20) one week after surgery, and the positive rate of complement C4d was 100% at 3 and 12 months after surgery. The cumulative survival rates at 1, 3, 5, and 7 years after surgery were all 100%. The cumulative survival rates at 1, 3, 5, and 7 years after kidney transplantation were 100%, 93.3%, 84.0%, and 84.0%, respectively. Except for 2 recipients who underwent transplantation in 2017 and experienced kidney failure at 30 and 49 months after surgery, all other transplanted kidneys survived. Conclusions: The results of routine renal transplant biopsy show that ABOi-KT has a good mid-term therapeutic effect. The pathological changes of ABOi-KT can be dynamically observed through routine renal transplant biopsy and targeted treatment for rejection reactions can be provided accordingly.

Influence of Chronic Forced Immobilization and Consumption of a High-Fat and High-Carbohydrate Diet Containing Cholesterol on Lipid and Cholesterol Metabolism in Male Wistar Rats.

We studied the effect of separate and combined influence of chronic forced physical activity reduction and high-fat and high-carbohydrate diet containing cholesterol on some indicators of carbohydrate, lipid, and cholesterol metabolism in growing male Wistar rats. Used combination of factors simulating a sedentary lifestyle and unhealthy diet did not have a synergistic effect on the selected biomarkers. On the contrary, the effect was antagonistic: body weight and appetite decreased and insulin resistance increased. The obtained results indicate certain prospects of hypercholesterolemia model using in preclinical studies of specialized food products to optimize the diet of individuals with disorders of carbohydrate and lipid metabolism.

The Expression of Markers of Acute Kidney Injury Kim1 and NGAL after Administration of High Doses of Lithium Carbonate in Mice with Engrafted Skin Melanoma B16.

The expression of marker proteins of acute kidney injury after administration of high doses of lithium carbonate was assessed to evaluate the possibility of lithium use in neutron capture therapy. In mice with implanted skin melanoma B16, the expression of Kim1 (kidney injury molecule 1) and NGAL (neutrophil gelatinase-associated lipocalin) proteins in the kidneys was evaluated immunohistochemically 15, 30, 90, 180 min, and 7 days after peroral administration of lithium carbonate at single doses of 300 and 400 mg/kg. An increase in the expression of the studied proteins was found in 30 and 90 min after administration of 400 mg/kg lithium carbonate, however, 7 days after the drug administration, the expression returned to the level observed in the control group. It can be suggested that single administration of lithium carbonate in the studied doses effective for lithium neutron capture therapy will not significantly affect the renal function.

Assessment of Autophagy in Tumor Cells of Human Skin Melanoma of Different Stages.

High levels of autophagy can increase the viability of tumor cells as well as their resistance to chemotherapy. Evaluation of the dynamics of autophagy processes at different stages of carcinogenesis can extend our understanding of melanoma pathogenesis to develop new therapeutic approaches. We performed a comparative study of tumor cell autophagy in stages II and III human skin melanoma. Tumor cells were characterized by high content of structures associated with autophagy (autophagosomes and autolysosomes). In stage III melanoma characterized by the presence of regional metastases in the lymph nodes, tumor cells showed higher expression of the autophagy marker protein LC3beta in comparison with stage II melanoma cells, which can indicate the involvement of autophagy processes in tumor progression and the formation of metastases in the lymph nodes.

Alpha Diversity Indices as Indicators of the Variability of Gut Microbiota in Obese Adolescents of Different Ethnicities.

We compared alpha diversity indices of the intestinal microbiota in adolescents with obesity and normal body weight, taking into account their ethnicity. Intestinal biocenosis was studied by metasequencing of amplicon libraries of V3-V4 fragments of the 16S rRNA gene. The alpha diversity of the microbiota was assessed using classical and alternative indices. Statistically significant differences in intestinal microbiota were observed between Russians with obesity and Buryats with normal body weight, as well as between Russians with obesity and Buryats with obesity when assessing the Shannon-Weaver, Chao1 indices, Faith phylogenetic diversity index, ACE, Fisher, Gini coefficient, Margalef, and Menkhinik indices. It was shown that alpha diversity indices can be used to assess significance of differences and variability of the intestinal microbiota in multifactorial diseases such as obesity in adolescents; however, the scope of application of the criteria should be considered.

[SRSF2 promotes glioblastoma cell proliferation by inducing alternative splicing of FSP1 and inhibiting ferroptosis].

Objective: To investigate the effect of serine/arginine-rich splicing factor 2 (SRSF2) on ferroptosis and its possible mechanism in glioblastoma cells. Methods: The online database of gene expression profiling interactive analysis 2 (GEPIA 2) and Chinese Glioma Genome Atlas were used to analyze the expression of SRSF2 in glioblastoma tissue and its association with patients prognosis. To validate the findings of the online databases, the pathological sections of glioblastoma and non-tumor brain tissues from Tianjin Medical University General Hospital, Tianjin, China were collected and analyzed by using immunohistochemistry. Silencing SRSF2 gene expression in glioblastoma cells by siRNA was analyzed with Western blot. The proliferation index was detected by using CCK8 assay. The rescued experiment was conducted by using expression plasmid of pcDNA3.1(+)-SRSF2. The activity of ferroptosis was assessed by using the levels of iron ions and malondialdehyde in glioblastoma cells and the changes in the ratio of glutathione to oxidized glutathione. The changes of gene expression and differential pre-mRNA alternative splicing (PMAS) induced by SRSF2 were monitored by using the third-generation sequencing technology analysis, namely Oxford nanopore technologies (ONT) sequencing analysis. Results: SRSF2 expression was higher in glioblastoma tissues than non-tumor brain tissues. Immunohistochemistry also showed a positive rate of 88.48%±4.60% in glioblastoma tissue which was much higher than the 9.97%±4.57% in non-tumor brain tissue. The expression of SRSF2 was inversely correlated with overall and disease-free disease survivals (P<0.01). The proliferation index of glioblastoma cells was significantly reduced by silencing with SRSF2 siRNA (P<0.01) and could be reversed with transfection of exogenous SRSF2. The levels of intracellulariron ions and malondialdehyde increased (P<0.05), but the glutathione/oxidized glutathione ratio and the expression of key proteins in the glutathione pathway remained unchanged (P>0.05). ONT sequencing results showed that silencing SRSF2 in glioblastoma cells could induce a significant alternative 3' splice site change on ferroptosis suppressor protein 1 (FSP1). Conclusion: SRSF2 inhibits the ferroptosis in glioblastoma cells and promotes their proliferation, which may be achieved by regulating FSP1 PMAS.

[Modern approaches to studying the molecular mechanisms of lung functioning in normal and pathological conditions]. / Sovremennye podkhody k izucheniyu molekulyarnykh mekhanizmov funktsionirovaniya legkikh v norme i pri patologii.

Problems with breathing and lung function are caused by the development of various lung diseases associated with lifestyle, harmful environmental factors and genetic predisposition. Knowledge of the molecular mechanisms of the development of the pathological process will allow on time identification of the disease or the development of targeted therapy. The article provides an overview of modern methods that make it possible to most accurately reproduce the structural, functional and mechanical properties of the lung (organ-on-a-chip), to perform non-invasive molecular studies of biomarkers of bronchopulmonary pathology using saliva diagnostics, as well as using DNA and RNA aptamers, verify tumor markers in biological samples of human tissue. Analysis of alterations in the pattern of protein glycosylation using glycodiagnostic methods makes it possible to detect lung cancer in the early stages.

[Changes in intraocular pressure and biometric parameters of the anterior segment of the eye after intravitreal injections]. / Izmeneniya urovnya vnutriglaznogo davleniya i biometricheskikh pokazatelei perednego segmenta glaza posle intravitreal'nykh in"ektsii.

PURPOSE: This study compares the changes in the parameters of the anterior chamber of the eye using anterior segment optical coherence tomography (AS-OCT) in patients with a natural and artificial lens after treatment of neovascular age-related macular degeneration (nAMD) by multiple intravitreal injections (IVI) of anti-VEGF drugs. MATERIAL AND METHODS: The patients were divided into 2 groups: group 1 (control) included 30 patients (30 eyes) with a natural lens, group 2 - 30 patients (30 eyes) with an intraocular lens (IOL). AS-OCT was performed using the Revo NX tomograph (Optopol, Poland) to analyze anterior chamber depth (ACD) and the parameters of anterior chamber angle (ACA). Intraocular pressure (IOP) was measured with a contact tonometer ICare Pro. RESULTS: In patients with an IOL, the IOP level 1 minute after intravitreal injection (IVI) of an anti-VEGF drug was statistically lower than in the control group, on average by 17.8% during the first IVI and by 28.7% after 1 year of observation (p<0.001). ACD before treatment was statistically significantly higher in patients with IOL compared to patients of group 1 by an average of 39.3% (p<0.001). ACA from the nasal and temporal sides in the meridian 0°-180° before the start of treatment was statistically significantly wider in phakic patients than in the control group, by an average of 15.9±9.3° (p<0.001) and 16.9±8.2° (p<0.001), respectively. According to AS-OCT, there was no shift of the iris-lens diaphragm in patients with an IOL after multiple IVI of an anti-VEGF drug, in contrast to the control group. CONCLUSIONS: AS-OCT was used to determine for the first time the changes in the parameters of the anterior chamber of the eye in patients with a natural and artificial lens after multiple injections of an anti-VEGF drug in the treatment of nAMD.

[Topical application of hypotensive drugs for the prevention of intraocular pressure elevation after intravitreal injections of anti-VEGF drugs]. / Mestnoe primenenie gipotenzivnykh preparatov s tsel'yu profilaktiki povysheniya urovnya vnutriglaznogo davleniya posle intravitreal'nykh in"ektsii anti-VEGF-preparatov.

The management protocol for patients with neovascular age-related macular degeneration (nAMD) involves multiple intravitreal injections (IVI) of anti-VEGF drugs. The ability to reduce the peak intraocular pressure (IOP) rise is greatly important in clinical practice. PURPOSE: This study evaluates the effect of topical hypotensive drugs on the short-term IOP rise after IVI of anti-VEGF drugs in patients with nAMD. MATERIAL AND METHODS: The prospective study included 80 patients with newly diagnosed nAMD. Before the start of treatment, the patients were divided into 4 groups of 20 people each: 1st - controls, who received no prophylactic drugs, in the 2nd, 3rd and 4th groups local instillations of one drop of hypotensive drugs brinzolamide 1%, brinzolamide-timolol, brimonidine-timolol were performed in the conjunctival sac twice: 1 day before the injection (at 20:00) and on the day of the injection 2 hours before the manipulation (at 08:00), respectively. IOP was measured in each patient using ICare Pro non-contact tonometer before injection, as well as 1 min, 30 and 60 min after injection. RESULTS: Prophylactic use of hypotensive drugs was associated with a significant decrease in IOP immediately after IVI compared to the same parameter in the 1st group (p<0.001), the maximum decrease in IOP values was observed when using a fixed combination of brimonidine-timolol by 12.1 mm Hg compared to the controls (p<0.001), the combination of brinzolamide-timolol reduced IOP by 8.5 mm Hg (p<0.001), brinzolamide 1% led to the smallest decrease in IOP - by 5.1 mm Hg (p<0.001). CONCLUSION: Study patients that received instillations of brimonidine-timolol combination of one drop into the conjunctival sac 1 day before the injection and on the day of the injection showed the maximum decrease in IOP compared to patients of the other groups.

[Treatment of primary malignant melanoma of the esophagus]. / Lechenie pervichnoi melanomy pishchevoda.

OBJECTIVE: To present treatment of primary esophageal melanoma in a young patient, as well as review of modern data on this issue. MATERIAL AND METHODS: We describe the results of treatment of a patient with primary melanoma of the esophagus. PubMed, SCOPUS, and elibrary databases were used for the review. RESULTS: We present a rare case of primary esophageal melanoma and variant of radical surgical treatment. The review is devoted to historical information about this nosology, statistical data, options for diagnosis and treatment. CONCLUSION: Such a rare clinical case is of great scientific interest due to the rarity of this disease. In our opinion, a certain register of orphan malignant tumors is necessary for diagnosis and treatment of various rare malignancies.

[Influence of chronic immobilization stress on vitamin status in rats fed different diets].

The influence of a stress factor, widespread in modern conditions, on the vitamin status has not been studied enough. At the same time, the negative stress impact can be aggravated against the background of unhealthy nutrition, which in turn affects the vitamin status of the organism. In this regard, the goal of the research was to evaluate the effect of chronic restrict stress on the vitamin supply in rats fed a diet with adequate and increased content of fat, sugar and cholesterol. Material and methods. The experiment was carried out on 37 growing male Wistar rats (initial body weight of 45±5 g) divided into 4 groups. Animals of the 1st (control) and the 2nd groups received a complete semi-synthetic diet (CSSD) (20% protein, 10% fat, 58% carbohydrates in the form of starch, 384 kcal/100 g) for 92 days. The levels of all vitamins and mineral elements in the rats' diets were adequate for growing rats. Rats of the 3rd and the 4th groups were fed a high-calorie, high-fat high-carbohydrate diet (HFHCD) (20% protein, 28% fat, 2% cholesterol, 18% carbohydrates in the form of starch, 20% sucrose, 511 kcal/100 g). Animals of groups 2 and 4 were subjected to daily 90-minute immobilization. The concentration of vitamins A (retinol and retinol palmitate) and E (α-tocopherol) in the blood serum and liver were determined by high-performance liquid chromatography, vitamins B1 and B2 in the liver and urine, as well as riboflavin in the blood serum and 4-pyridoxic acid (4-PA) in urine were determined by fluorimetric methods. Biochemical parameters of blood serum were determined on a biochemical analyzer; the total content of fat, triglycerides (TG) and cholesterol (CH) was determined in the liver. Results. Replacing CSSD with HFHCD, both under restraint stress and without, was accompanied by an increase in liver weight by 1.8-2.0 fold, in its fat content by 2.6-3.3 fold, cholesterol by 32.6-35.3 fold and TG - by 33.0-57.6 fold (p=<0.001). An increase in alanine aminotransferase (ALT) activity by 1.7-2.0 fold (p=<0.01), in low-density lipoprotein (LDL) cholesterol level by 5.4 fold (p=<0.05) and the atherogenic coefficient by 2.5 fold (p<0.01) as well as a decrease in creatinine and urea level (p=<0.05) in blood serum were revealed. Immobilization was accompanied by a decrease in body weight, liver and liver fat in rats fed both CSSD and HFHCD (p<0.05), but didn't affect the blood serum biochemical parameters, with the exception of an increase in ALT activity. If the activity of alkaline phosphatase (ALP) did not change during immobilization of rats fed the CSSD, then in animals fed the high-calorie diet it decreased by 37.5% (p=<0.05 from the control) under its increase against the background of restrict stress by 78.7% (p=<0.01) compared to the indicator of rats of the 3rd group. Immobilization of rats treated with CSSD was accompanied by an increase in both absolute serum α-tocopherol level and concentration correlated with the level of cholesterol and triglycerides by 26.0-57.5% (p<0.05), with a simultaneous decrease in its content in the liver per 1 g of wet tissue by 22.1% (p=0.041) relative to the indicators of intact animals. Immobilization reduced the level of retinol palmitate in the liver by 2.3 times (p<0.01), but did not affect retinol level in the blood serum. At the same time, indicators of B vitamin status (the content of vitamins B1 and B2 in the liver per 1 g of wet tissue and per organ, blood serum riboflavin level, urinary excretion of riboflavin and 4-PA) did not change, with the exception of thiamine urinary excretion, which reduced compared to the control by 38.8%. In rats fed HFHCD, immobilization had no additional effect on the supply with vitamins A and E. The content of vitamins B1 and B2 in the liver in terms of the whole organ was reduced by 14.0-26.7% relative to the indicator in animals of the 3rd group, not subjected to chronic stress, only due to differences in liver weight in animals of these groups. Conclusion. The data obtained indicate that chronic stress has a negative effect on the vitamin status of the body, worsening the supply with vitamins A, E and B1, and substantiate the feasibility of studying the mechanisms of this effect in order to develop effective vitamin complexes for the treatment and prevention of diseases caused by long-term stress.

[Treatment of malignant effusion]. / Sravnitel'naya kharakteristika metodov lecheniya metastaticheskogo plevrita (obzor literatury).

Malignant effusion complicates more than 15% of all cancers in delayed stages of progression. The most common causes of metastatic pleuritis are lung cancer, breast cancer, ovarian cancer, lymphoproliferative diseases or dissemination of gastrointestinal tumors. Malignant effusion is associated with negative prognosis for overall survival regardless of etiology of tumor, significantly complicates the course of the underlying disease, impairs life quality and complicates treatment. Despite various methods for pleural cavity obliteration in recurrent metastatic pleuritis, there is still no a uniform approach to choosing the optimal treatment strategy. We analyzed the main methods of conservative and surgical treatment of recurrent metastatic pleuritic regarding efficacy, risk of recurrence and reproducibility.