Pathologia

Expression of angiotensin-converting enzyme-2 (ACE2) in experimental diabetic retinopathy and influence on it of cellular protein kinases blockade

K. O. Usenko — 2025-08-30

Disruption of the renin-angiotensin system (RAS) of the eye is a causal factor in diabetic microvascular complications. The effects of RAS are counteracted by a recently discovered axis involving angiotensin-converting enzyme type 2 (ACE2) and its product angiotensin 1-7.

Aim: to determine the expression and content of ACE2 in the retina in experimental diabetic retinopathy (DR) and to establish the effect of blockade of cellular protein kinases on them.

Materials and methods. DR was modeled in male Wistar rats. For this purpose, they were administered streptozotocin once at a dose of 50 mg/kg (Sigma-Aldrich, Co, China). Experimental rats were divided into four groups: control; with the administration of insulin 30 U (NovoNordiskA/S, Bagsvaerd, Germany); with the administration of the protein kinase inhibitor sorafenib (Cipla, India) at a dose of 50 mg/kg; with the administration of insulin and sorafenib. During immunoblotting and immunohistochemical studies, monoclonal antibodies against ACE2 (EMD Millipore Corporation, USA) were used.

Results. A multiple increase in the content of ACE2 in the diabetic retina was established, first the accumulation of its free isoforms, and then binding to cellular proteins. Also, during the observation, an increase in the expression of ACE2 in the vessel walls was noted, which confirmed the involvement of this important RAS regulator in the pathogenesis of diabetic retinal damage. Insulin administration reduced the content of ACE2 after 21 days and 2 months of treatment to a greater extent than its combined administration with sorafenib, or separate administration of sorafenib. After 3 months, the content of ACE2, especially its high-molecular forms, was more effectively reduced by the combined administration of insulin with sorafenib than by separate administration of insulin.

Conclusion. The results obtained showed a possible role of increased ACE2 expression in the pathogenesis of DR and revealed its decrease during treatment with insulin and sorafenib, which corresponded to the inhibition of the development of morphological signs of DR.

Assessment of changes in carbohydrate metabolism parameters in rats with experimental diabetes mellitus of different origins under L-arginine and N-acetyl-L-cysteine administration

M. I. Isachenko — 2025-08-30

The aim: to determine the specificity of changes in carbohydrate metabolism in rats with experimental type 1 (DM1) and type 2 (DM2) diabetes mellitus and to analyze correlations of their modification under administration of the amino acids L-arginine and N-acetyl-L-cysteine.

Materials and methods. DM1 was induced in old male Wistar rats by a single 45 mg/kg streptozotocin. In rats with DM2, insulin resistance was first induced (high-fat mixed feed for 8 weeks), after which 30 mg/kg streptozotocin was administered once. After 6 weeks, animals with DM were divided into 3 subgroups: without amino acid administration, rats with L-arginine and with N-acetyl-L-cysteine.

Results. Experimental modeling of DM1 resulted in persistent hyperglycemia and hypoinsulinemia, which significantly altered metabolic indices. In rats with DM2, hyperglycemia developed with hyperinsulinemia, indicating established insulin resistance. Administration of L-arginine and N-acetyl-L-cysteine to rats with both types of diabetes lowered glucose levels and increased insulin concentrations, although no statistically significant difference was found between the effects of these amino acids. L-arginine significantly increased the HOMA-β index in rats with DM1 and moderately increased it in rats with DM2. In addition, it caused a significant increase in the HOMA-IR index in the group with DM1, indicating improved insulin sensitivity. N-acetyl-L-cysteine also improved HOMA-β and HOMA-IR indices in rats with DM1, although its effect on DM2 was less pronounced and did not reach statistical significance.

Conclusions. In rats with type 1 diabetes, both amino acids cause a decrease in glucose concentration, which is due to improved pancreatic β-cell function due to increased insulin concentration, the HOMA-β index compared to the subgroup without correction, but also causes an increase in the HOMA-IR index, and the listed indicators do not return to control values. These changes were accompanied by profound disruption of metabolic relationships, which is confirmed by correlation analysis. Against the background of the development of type 2 diabetes mellitus, both amino acids reduce glucose concentration and increase insulin compared to the subgroup without correction, however, the HOMA-β index improves only in rats with L-arginine, and the preserved hyperinsulinemia in all 3 subgroups leads to an increase, compared to the control, in the HOMA-IR index without a significant difference between the effects of amino acids. Correlation analysis revealed greater preservation of metabolic relationships of carbohydrate metabolism indicators compared to rats with type 1 diabetes mellitus.

Morphological features of intrahepatic bile duct injury in children with autoimmune liver diseases

M. B. Dyba — 2025-08-30

Involvement of small intrahepatic bile ducts is a characteristic but underexplored feature of autoimmune liver diseases (AILD) in children. A distinctive aspect of pediatric AILD is the overlap between autoimmune hepatitis (AIH) and primary sclerosing cholangitis (PSC), which complicates differential diagnosis – especially in cases with isolated small-duct injury and absence of typical PSC features on MRCP.

The aim of the study was to assess the spectrum and frequency of biliary injury in children with autoimmune hepatitis, autoimmune sclerosing cholangitis, and primary sclerosing cholangitis using the modified Nakanuma scoring system and additional morphological criteria of cholestasis.

Materials and methods. Sixty-nine children with AILD were included: 26 with AIH, 29 with ASC, and 14 with PSC. Liver biopsies were evaluated using the Nakanuma classification. Additional features assessed included periductal fibrosis and signs of cholestasis (biliary interface, rosettes, ballooning / feathery hepatocyte degeneration, portal / periportal edema, and mucobilia).

Results. The median age at diagnosis was 11 years (IQR: 8–14). Advanced liver fibrosis (F3–F4) was present in 54 % of AIH, 79 % of ASC, and 43 % of PSC cases. Cirrhosis was observed in 24 % of ASC, 19 % of AIH, and 7 % of PSC patients. Inflammatory bowel disease was common in biliary phenotypes – detected in 72 % of ASC and 71 % of PSC patients, and in only 3.8 % of AIH cases. According to MRCP, large-duct involvement was seen in 71 % of PSC and 72 % of ASC patients, while isolated small-duct injury was found in 29 % and 28 %, respectively. ASC and PSC patients showed a broader range of biliary lesions compared to AIH. Statistically significant differences were observed in the frequency of ductopenia ≥ grade 2 (ASC – 52 %, PSC – 64 %, AIH – 19 %), advanced periductal fibrosis ≥ grade 3 (ASC – 62 %, PSC – 71 %, AIH – 8 %), and mucobilia (ASC – 66 %, PSC – 36 %, AIH – 4 %; p < 0.001). Cumulative scoring of biliary features reliably distinguished AIH (mean 3.4 ± 1.4) from ASC (6.4 ± 1.6) and PSC (6.7 ± 1.9, p < 0.001).

Conclusions. Extended morphological analysis using the Nakanuma classification and additional biliary injury criteria improves diagnostic accuracy for identifying the biliary phenotype of AILD in children, including small-duct variants of ASC and PSC. This approach supports more precise diagnosis and individualized treatment strategies.

Dynamics of TGF-1β and MMP-9 content in the serum of patients with chronic hepatitis C infected with HCV GT1 on the background of antiviral treatment depending on the severity of liver fibrosis

O. V. Riabokon — 2025-08-30

The aim: to analyse the dynamics of TGF-1β and MMP-9 in the blood serum of patients with chronic hepatitis C (HCV) infected with HCV GT1 on the background of antiviral treatment depending on the severity of liver fibrosis.

Materials and methods. The study included 92 patients with GT1 HCV infection treated with antiviral therapy (AVT) – OBV / PTV / r+DSV±RBV. The severity of liver fibrosis was determined by elastometry. The content of TGF-1β (Elabscience, USA) and MMP-9 (Elabscience, USA) in the blood serum was determined by ELISA.

Results. In patients with CHC GT1 before the start of AVT, profibrogenic potential prevailed: increased TGF-1β (p < 0.05), decreased MMP-9 (p < 0.05) and a higher TGF-1β / MMP-9 ratio (p < 0.05). AVT (OBV / PTV / r+DSV±RBV) slows down fibrogenesis and activates antifibrotic processes, which is confirmed by an increase in MMP-9 (p < 0.05) and a decrease in TGF-1β / MMP-9 (p < 0.05) compared to the pre-treatment values. Prior to AVT, patients with GT1 HCV with liver fibrosis F 0–2 had lower MMP-9 levels (p < 0.05) than healthy subjects, with no changes in TGF-1β and TGF-1β / MMP-9 ratio (p > 0.05). In patients with F 3–4 liver fibrosis, serum TGF-1β and the TGF-1β / MMP-9 ratio were higher, and MMP-9 was lower, both compared with healthy subjects (p < 0.05) and compared with patients with F 0–2 (p < 0.05). In patients with F 0–2, at the time of completion of AVT, the studied parameters do not differ from healthy individuals (p > 0.05). In patients with F 3–4 at the time of completion of AVT, the TGF-1β / MMP-9 ratio remains higher both in comparison with healthy individuals (p < 0.05) and in comparison with patients with CHC GT1 with liver fibrosis F 0–2 (p < 0.05).

Conclusions. We demonstrated more significant dynamics of antifibrotic changes during direct-acting antiviral agents based AVT in patients with GT1 CHC in the presence of F 0–2 liver fibrosis compared to patients with F 3–4.

Pathomorphological brain changes due to coronavirus disease 2019 (COVID-19)

L. I. Volos — 2025-08-30

Aim: To investigate the pathomorphological changes in the brains of individuals who died from complications of coronavirus disease (COVID-19) and to identify the neuropathological features associated with COVID-19.

Materials and methods. A morphological study was conducted on autopsy material from 78 individuals who died due to complications of COVID-19 between March 2020 and April 2021. Histological examinations of various brain regions – including the cortex, white matter, basal ganglia, hippocampus, brainstem, and cerebellum – were performed using both morphological and immunohistochemical methods. Monoclonal antibodies were used to detect astrocytes (GFAP, Thermo Scientific), microglia (CD68, Clone Ab-4, Thermo Scientific), and T-lymphocytes (CD3, Clone SP7, Thermo Scientific). Histological evaluation and microphotography were carried out using a Leica DM750 universal optical microscope (Leica Microsystems GmbH).

Results. It was found that brain damage in hospitalized patients with SARS-CoV-2 infection was associated with older age, disease severity, and comorbidities. In cases of severe COVID-19 with neurological deficits, neurovascular incidents were accompanied by ischemic infarction, venous sinus thrombosis, and intracerebral hemorrhage. Hypoxic-ischemic encephalopathy was histologically characterized by degeneration and partial loss of neurons, microglial activation with the formation of numerous microglial nodules in the cortex around hypoxically altered neurons, in the white matter, perivascularly, and in perivascular spaces throughout different parts of the brain, reactive astrogliosis with a positive immunohistochemical marker GFAP, and perivascular infiltration by T-lymphocytes.

Conclusions. Since SARS-CoV-2 has a broad tissue tropism, both respiratory and extrapulmonary complications can occur. The neuropathological features and findings in the studied cases with a severe course included neuronal degeneration, microglial activation, infiltration by CD3-positive T-lymphocytes, reactive astrogliosis, and, in some cases, macroscopic abnormalities such as fresh and old ischemic infarctions and hemorrhages.

Content of micro- and macroelements in patients with autoimmune thyroiditis and subclinical hypothyroidism

V. I. Kravchenko — 2025-08-30

Aim. To investigate the content of iodine (I), selenium (Se), zinc (Zn), magnesium (Mg), calcium (Ca) and vitamin D, the thyroid volume and thyroid functional state in patients with autoimmune thyroiditis (AIT) and subclinical hypothyroidism (SCH), to assess the elemental supply, possibilities and feasibility of preventive and therapeutic use of micro- and macronutrients in the early stages of the disease.

Materials and methods. 134 people were examined (13 men, 121 women). Within the entire sample, 2 groups were formed depending on the presence of functional and laboratory signs of the disease: 1st – control group consisted of 53 healthy individuals without endocrine pathology, average age – 37.9 ± 11.8 years, of which 8 were men (15.10 %), and 2nd group with AIT and SCH – 81 people, average age – 40.0 ± 11.1 years, of which 5 were men (6.17 %). Anthropometric parameters were determined: age, sex, height, weight, body mass index; thyroid functional state: total thyroid volume, concentration of thyroid-stimulating hormone (TSH), free thyroxine (fT4), free triiodothyronine (fT3), level of antibodies to thyroid peroxidase (TPOAb), level of antibodies to thyroglobulin (TgAb); level of micro- and macroelement: I in urine, Se, Mg, Ca, vitamin D in serum.

Results. In the group with AIT and SCH, a significant (p < 0.001) increase in thyroid volume, TSH, TPOAb and TgAb levels and a significant decrease in thyroid hormones fT4 (p = 0.008), fT3 (p < 0.001) were found compared to the control group. In both groups, a slight iodine deficiency in the urine and a deficiency of vitamin D in the serum compared to reference values were noted. In the group of patients with AIT and SCH, a significant decrease in Se (p = 0.016), Mg (p < 0.001) and total Ca (p < 0.001) was found compared to the control. A pronounced positive correlation of Se / I (r = 0.691) was found. The statistically significant Odds ratio of AIT progression and overt hypothyroidism with reduced Mg content is OR = 2.80 (95 % CI 1.29–6.09, p = 0.0094), with reduced Ca content – OR = 7.68 (95 % CI 2.77–21.30, p = 0.0001).

Conclusions. The group with AIT and SCH and the control group have a weak iodine deficiency in the urine and vitamin D deficiency in the blood serum compared to normal reference values, which indicates a general population deficiency. In the group of patients with AIT and SCH, a significant decrease in serum Se, Mg and total Ca was found compared to the control. A significant positive correlation Se / I (r = 0.691) indicates the relationship of these trace elements and confirms their combined effect on the development of autoimmune disorders and thyroid hormonal changes. A high risk of progression of AIT and overt hypothyroidism exists with reduced Mg and Ca content.

Analysis of clinical and morphological features of common forms of pustular psoriasis

M. E. Zapolskyi — 2025-08-30

In recent decades, the frequency of cases of widespread forms of pustular psoriasis has significantly increased, which are often mistaken for other chronic dermatoses: eczema, bullous toxidermia, herpes, Andrews’ pustular bacterid, subcorneal pustulosis, etc. – and as a result, late appointment of adequate treatment, severe course of the disease, possible fatal outcome.

The aim of the work is to analyze the histological features of widespread forms of pustular psoriasis depending on the clinical manifestations of dermatosis.

Materials and methods. 57 patients with pustular forms of psoriasis were under observation: 34 (60 %) patients with limited forms of pustular psoriasis, 23 (40 %) – with widespread forms (12 of them – with widespread and 11 – with generalized). All patients with widespread forms of pustular psoriasis underwent histological examination twice by punch biopsy: before the start of treatment and 7 days after the disappearance of pustular elements from the foci of background erythema. The obtained samples were stained with hematoxylin and eosin.

Results. When analyzing the clinical features of pustular psoriasis, it was found that a characteristic feature of widespread forms, in addition to multiple pustules, was persistent background erythema, which appeared in most patients at the beginning of the disease, persisted for a long time, even after the end of treatment, and the degree of its manifestations correlated with the severity of the disease. Histological analysis of the material taken from the foci of grouped pustules and background erythema revealed a relationship between the intensity of background erythema, the nature of morphological changes in the skin and the long-term prognosis of dermatosis.

Conclusions. Background erythema is an important diagnostic criterion for common forms of pustular psoriasis, characterizing the degree of neutrophilic infiltration of the skin, the risk of fresh pustules and the progression of dermatosis in general.

Determination of the structural composition of biopsies from the maxillary sinus augmentation zone using the NanoGraft material

O. S. Kosinov — 2025-08-30

Aim. This study aimed to evaluate the structural composition of biopsy samples from the augmented maxillary sinus region using the NanoGraft biomaterial.

Materials and methods. Biopsy specimens from sinus lift procedures involving NanoGraft were histologically examined. Samples were fixed in 10 % neutral buffered formalin for 48–72 hours, decalcified using a rapid decalcifier (Kaltek, Italy), and processed in paraffin using an automated tissue processor (Milestone LOGOS, Milestone, Italy). Paraffin blocks were prepared with the HistoStar embedding workstation (Thermo Fisher Scientific, USA), and 4 µm serial sections were obtained using the Thermo Scientific HM 340E rotary microtome. Sections were stained with hematoxylin and eosin (Dako CoverStainer, Agilent, USA), and toluidine blue staining was performed manually. Morphological analysis was carried out using a Leica light microscope to assess bone structure, surrounding connective tissue, resorption dynamics, and new bone formation.

Results. All samples revealed newly formed trabecular bone, active osteogenesis, and progressive remodeling, with replacement of coarse fibrous bone by lamellar bone containing osteons. No significant inflammatory response to the biomaterial was observed.

Conclusions. NanoGraft exhibited high biocompatibility, along with osteoinductive and biostimulatory properties, making it a promising material for maxillary sinus augmentation procedures.

mtDNA copy number: molecular diagnostics and mitochondrial-nuclear crosstalk in frailty and ageing

C. G. Ward — 2025-08-30

Quantitative assessment of mitochondrial DNA copy number is an emerging field of study in the diagnosis and evaluation of age-related pathology and frailty in the elderly, along with the assessment of other acute and chronic diseases that are often necessary within this patient cohort.

Aim: to analyze current advances in the quantitative assessment of mitochondrial DNA copy number as a tool for diagnosing and evaluating age-related pathology, frailty, and comorbid conditions in the elderly.

Material and methods. The author independently conducted a thorough review of literature available from the NIH, PubMed database, providing a detailed narrative of updates in the field. As clinical trials seek to further develop practical techniques, the author then undertook a search of relevant trials at ClinicalTrials.gov, including this as a table in the body text.

Results. The review provides a thorough examination of the theoretical foundation of mitochondrial biogenesis, fusion-fission processes, and control and repair of mitochondrial genetic material, and how advances in these topics may be applied to better understand the processes being measured in quantitative mitochondrial DNA analysis.

Conclusions. Detailed examination of the crosstalk between mitochondrial control proteins and nuclear factors, and the fundamental role of energy homeostasis apparatus within ageing processes underpins the advances in translational aspects of mitochondrial medicine and allows more effective exploitation of this emerging field.

Osteoporosis in postmenopausal women: pathogenetic relationships with coronary heart disease and obesity (literature review)

N. S. Mykhailovska — 2025-08-30

Aim: to summarize and analysis of current literature data on the pathophysiological mechanisms of the relationship between osteoporosis, coronary heart disease and obesity in postmenopausal women.

Materials and methods. A systematic analysis of scientific publications presented in the databases PubMed, Scopus, Web of Science, Google Scholar, as well as in national medical information resources of Ukraine was conducted. The work included scientific articles that met the inclusion criteria for the topic, completeness of the text, and relevance.

Results. Osteoporosis, coronary heart disease, and obesity are the three most common diseases among postmenopausal women, which have a high level of medical and social significance due to their chronic course, high incidence of complications, and impact on functional capacity and quality of life. Estrogen deficiency in postmenopausal women is a key trigger for pathological changes in bone, metabolic, and vascular homeostasis.

Recent studies demonstrate the presence of common pathogenetic links for these conditions, such as chronic low-level inflammation, endothelial dysfunction, estrogen deficiency, insulin resistance, lipid metabolism disorders, and adipokines imbalance. Decreased bone mineral density (BMD) correlates with atherosclerotic vascular lesions, and vascular calcification is often accompanied by bone loss. Osteotropic proteins are also found in vascular walls, indicating a biological transition between bone and vascular tissues. Low BMD is associated with an increased risk of cardiovascular mortality, especially in the elderly.

Obesity also has a systemic negative impact on bone and cardiovascular health through activation of pro-inflammatory cytokines and stimulation of bone resorption. However, the current literature contains conflicting data on the impact of obesity on BMD: moderate excess body weight may have a protective effect on BMD loss, but obesity of II–III degree is significantly associated with an increased risk of osteoporotic fractures. This necessitates the need for risk stratification taking into account the degree of obesity and concomitant cardio-metabolic pathology.

Conclusions. The presence of common pathogenetic mechanisms of osteoporosis, coronary heart disease, and obesity confirms the feasibility of developing comprehensive approaches to the prevention, early diagnosis, and treatment of these conditions in postmenopausal women.

Interdisciplinary approach to the management of patients with perforating dermatosis (clinical case)

V. A. Vizir — 2025-08-30

The aim of this work is to describe a clinical case of acquired perforating dermatosis within the context of an interdisciplinary approach to patient management, taking into account a comprehensive therapeutic and dermatological diagnostic and therapeutic algorithm.

Materials and methods. A personal observation is described of a 70-year-old patient with clinical manifestations of acquired perforating dermatosis and multimorbid somatic pathology, the verification of which was carried out taking into account the results of laboratory and instrumental diagnostic methods. The dermatological diagnosis was established based on the morphological assessment of a skin biopsy.

Results. A clinical case of a patient with skin lesions of the trunk and upper extremities is described. Visual manifestations of dermatosis are represented by a papular rash with a central depression, erosions, hyperkeratotic changes, and pronounced itching, which in general mimic a wide range of nosologies: from lichen planus, prurigo to multiple keratoacanthomas. Given such clinical non-specificity of the pathological process on the skin, only morphological diagnostics can contribute to the final verification of the dermatological diagnosis. In addition, an important aspect was the assessment of the patient’s somatic status, which revealed the presence of multimorbidity, in particular concomitant cardiovascular pathology, chronic kidney disease, cryptogenic liver cirrhosis, and portal hypertension. The general therapeutic direction of this disease is to compensate for the underlying somatic pathology. That is why, given the clinical complexity of the condition, patients in this category require the mandatory involvement of physicians from related specialties. In this case, the patient requires constant therapeutic support, including in the conditions of an inpatient ward. Given the severe general status of the patient, it was decided, in parallel with the treatment of somatic pathology, to have a rather gentle effect on the efflorescence, only with the use of systemic antihistamines and topical therapy with glucocorticosteroids. The positive dynamics within the skin justify the expediency of continuing the planned comprehensive therapeutic tactics.

Conclusions. Morphological examination is the gold standard for verifying pathological processes in the skin. Considering the rather variable nosologies in the context of multimorbidity in one patient, as well as the clear dependence of the course of dermatosis on somatic pathology, a mandatory stage in the management of such patients is the joint interdisciplinary work of specialists of both dermatological and therapeutic profiles.