This article commemorates the 155^th anniversary of the birth of G.M. Iosifov, head of the Department of Human Normal Anatomy at the Faculty of Medicine of Voronezh State University, which was reorganized in 1930 into the Voronezh State Medical Institute. Professor G.M. Iosifov was a prominent anatomist and founder of both the Voronezh and Russian school of lymphology. However, very little is known about his Voronezh period. This article presents for the first time the results of a study of documents from the State Archive of Voronezh Region (SAVO) and the State Archive of the Russian Federation (SARF) pertaining to the Voronezh period of Hordey Maximovich Iosifov’s life and work. It features materials on the scientific, educational, and public activities of this talented scientist and educator, along with insights into the historical circumstances of his life and career.

Chronological aging is defined as the time-dependent decline in tissue homeostasis, which significantly affects the skin. Elucidating the mechanisms of skin aging is a priority in modern research, though limited by the lack of appropriate in vitro models. As a component of aging, replicative or stress-induced senescence is widely used to simulate skin aging in vitro. The aim of the study is a comparative assessment of age-related morphological and molecular changes in primary cultured fibroblasts derived from individuals over 45 years old and under 15 years old. Material and methods. This study investigated primary normal human dermal fibroblasts isolated from young and elderly donors, focusing on their age-related characteristics during 2D monolayer culture and their potential use as a relevant model for studying aging processes. We employed fluorimetry to analyze proliferation, assessed clonogenic activity, and evaluated various indicators of regenerative potential, including elastase activity, gene expression, and mitochondrial DNA (mtDNA) content. Data were statistically analyzed using multiple descriptive statistics. Differences were considered statistically significant at p<0.05. Results. A marked decline in the population doubling ability, reduced clonogenic capacity, impaired extracellular matrix production along with modifications in respiratory metabolism were observed with increasing age. These impairments were particularly evident when comparing fibroblasts isolated from individuals over 45 years old with those from participants younger than 15 years, while cells from middle-aged donors exhibited an intermediate profile. Conclusions. The observed changes in cell properties may be associated with signs of dermal aging, supporting the assumption that cultured primary cells indeed retain some characteristics of the original tissue from which they were derived. The findings have both scientific and practical significance for modeling studies on the mechanisms of aging, understanding the mechanisms of regenerative repair at different ages, and for targeted interventions, such as in the treatment of gingival recession in patients of varying ages.

The aim was to use immunohistochemistry to assess the dynamics of p53, casp3, and bcl-2 protein expression in rat skin connective tissue cells during the stages of post-traumatic histogenesis. Material and methods. The experiment was performed on male Wistar rats (n=40) weighing 200–230 g. A deep transverse incisional skin wound was created in the middle third of the thigh using a sharp scalpel. Specimens were obtained at 12 hours, 24 hours, 2, 3, 6, 10, 15, and 25 days following injury, using 5 animals for each time interval. Five intact animals served as controls. Expression of p53, caspase-3, and bcl-2 was assessed immunohistochemically. Data analysis employed parametric statistical approaches. Results. When mechanical damage occurs in skin connective tissues – comprising both loose and dense irregular connective tissue of the dermis and hypo- dermis, along with hypodermal adipose tissue – this induces predictable histogenetic processes in the perine- crotic wound region, including programmed cell death activation. Key findings revealed distinct patterns of p53, casp3, and bcl-2 protein expression. The study demonstrated distinct expression patterns of apoptotic markers proteins during both: the necrotic and inflammatory phases of wound healing, and the proliferative, differentiation, and adaptive phases of regenerative histogenesis. Conclusion. The proportion of p53-, casp3-, and bcl-2- positive cells varied significantly across different wound healing phases. Maximal Casp3+ cell counts occurred at two time points: during the acute inflammatory phase (day 2) and subsequently during tissue differentiation (day 10). Peak p53+ cell counts were observed at three time points: during acute inflammation (24 h and day 3), and later during regenerative histogenesis (day 15). Significant peaks in Bcl-2 immunopositive cells were detected at three time points: 24 hours, 6 days, and 15 days following trauma.

The aim was to investigate the microscopic structural features of the entheses of the fifth metatarsal bone in men of the first mature age period. Material and methods. The study examined the microscopic features of the entheses of the fifth metatarsal bones bilaterally in 56 cadaveric specimens from males aged 21–35 years. Tissue specimens from the typical ligament and tendon attachment sites at the head and base of the fifth metatarsal bone were histologically analyzed using Masson’s trichrome staining. The thickness of enthesis zones was measured, and the organization of collagen fibers was analyzed with quantification of their percentage content in relation to adjacent structures using light microscopy of scanned histotopograms. Results. The study revealed that all four ligamentous and tendinous connections of the fifth metatarsal demonstrate fibrocartilaginous entheses comprising four distinct zones that structurally form a continuous transition from soft connective tissue to osseous tissue. Results showed greater thickness of the calcified versus mineralized fibrocartilage zones in the peroneus brevis tendon, plantar metatarsal, and collateral ligament entheses, featuring parallel wavy collagen fibers with scattered mature chondrocytes and isogenous groups. The maximal thickness of the calcified fibrocartilage zone was identified in the deep transverse metatarsal ligament enthesis, characterized by linearly oriented collagen fibers and abundant chondrocyte isogenous groups. The study determined the minimal thickness of the calcified fibrocartilage zone in the tarsometatarsal and long plantar ligament enthesis complex, exhibiting a disordered arrangement of collagen fibers and numerous mature chondrocytes organized in isogenous groups. Basophilic demarcation lines with serrated morphology in virtually all enthuses was documented. The most pronounced serrations (in both thickness and amplitude) were registered at the peroneus brevis tendon attachment site, while the deep transverse metatarsal ligament exhibited a characteristically attenuated and flattened basophilic line. A decreasing collagen gradient from calcified to mineralized zones was established in the peroneus brevis tendon and tarsometatarsal-long plantar ligament entheses, while the deep transverse metatarsal ligament exhibited an inverse pattern. The plantar metatarsal and collateral ligament entheses maintained equivalent collagen proportions across zones. Conclusion. The investigation of microarchitectural characteristics in fifth metatarsal entheses provides evidence supporting the probable existence of distinct structural patterns influenced by age, sex, and body constitution, which may correlate with differential susceptibility to mechanical trauma.

The aim is to assess the diagnostic value of applying regional ultrasound fetometry standards for verifying intrauterine growth restriction (IUGR) in the pregnant population of the Kirov region. Material and methods. The analysis included data from 320 full-term newborns diagnosed with IUGR, delivered at the Kirov Regional Clinical Perinatal Center between 2021 and 2023. Three IUGR subtypes were distinguished among the newborns: hypotrophic, hypoplastic, and dysplastic. The hypotrophic subtype is characterized by low birth weight with normal body length and head circumference, which corresponds to asymmetric fetal growth restriction on prenatal ultrasound fetometry. The hypoplastic subtype, consistent with symmetric fetal growth restriction on prenatal ultrasound, demonstrates proportionate deficits in birth weight, length, and head circumference compared to expected gestational age standards. The dysplastic subtype combines growth restriction with fetal malformations. We also performed a retrospective analysis of 374 maternal ultrasound scans, applying both national reference standards and our institutionally developed regional fetal growth parameters. Results. The sensitivity of ultrasound fetometry using regional norms reached 82.3% (asymmetric form) and 88.2% (symmetric form), substantially exceeding the sensitivity achieved with federal standards (30.9% and 71.1%, respectively). Meanwhile, the specificity of the method demonstrated a modest reduction with regional standards yet maintained high diagnostic performance. Conclusion. Regional ultrasound biometry standards significantly increase IUGR detection sensitivity by incorporating local population characteristics. Their clinical adoption in the Kirov region is recommended for improved fetal growth restriction diagnosis.

So far, a number of contradictory data have accumulated regarding not only the timing and characteristics, but also the very fact of age-related involution of the largest of the extra-adrenal chromaffin paraganglia – the lumbar para-aortic paraganglion (LPP, organ of Zuckerkandl). The aim is to investigate the features of age-related transformations of the LPP in postnatal ontogenesis. Material and methods. Using histological and histochemical methods on complete serial sections, the organ complexes of the area of location of the LPP of rats in the main periods of postnatal ontogenesis (0–1, 7–8, 14, 21 days, 1, 3, 6–8, 14 months and 2 years). Results. All newborn animals have a well-developed LPP, which contains arrays of chromaffin cells with a moderate chromaffin reaction and heterogeneous groups of slightly differentiated cells. The size and number of chromaffin cells in the LPP decrease (according to a number of signs via autophagy) while the presence of nerve cells increases from the end of the 1st postnatal week. This leads to the transformation of the LPP into a mixed chromaffin-nerve ganglion, then into a typical nerve ganglion. Chromaffin cells in the LPP area completely disappear by the 1st month. Groups of chromaffin cells with intense chromaffin reaction reappear in the LPP area nerve ganglia starting from 3 months, then their number and size increase until old age. We associate the causes of age-related LPP involution with the activation of adrenal medulla maturation during the same period and the secondary appearance and hypertrophy of chromaffin cells in the LPP area with increased stress effects during maturation and weakening of the cardiovascular system during aging. Both factors cause an increase in the level of glucocorticoids which are stimulators of the proliferation of extra-adrenal chromaffin tissue. Conclusion. The rat LPP demonstrate a pronounced age-related involution, accompanied by the replacement of chromaffin tissue by nervous tissue from the 1st to the 4th postnatal weeks. After the completion of age-related involution of the LPP, clusters of chromaffin cells appear for the second time in the nerve ganglia of this area, progressing as growing up and ages.

Squamous cell carcinomas of the vulva are classified into human papillomavirus (HPV)- associated and HPV-independent types. The mechanisms of carcinogenesis at this site remain poorly understood. The aim of the study is to compare mitotic activity and the number of multinucleated tumor cells in HPV-associated and HPV-independent vulvar carcinoma. Material and methods. This retrospective study included 74 patients with newly diagnosed vulvar squamous cell carcinoma. Immunohistochemical analysis and viral typing using polymerase chain reaction were performed. Quantification of mitotic figures (including atypical forms) and multinucleated tumor cells was conducted in 20 consecutive ×400 magnification fields. Evaluation included 74 tumor specimens and 18 matched normal tissue controls. Results. We observed HPV-positive status in 21 cases (28.4%), with 53 tumors (71.6%) classified as HPV-negative. HPV-positive patients showed younger age at diagnosis (65 [57–76] years) compared to HPV-negative cases (75 [68–82] years). HPV- associated tumors were diagnosed at earlier disease stages (Stage I-II) in 71.4% of cases compared to HPV- independent vulvar carcinomas (47% at Stage I-II). HPV-positive tumors demonstrated significantly elevated mitotic activity (37 [31.25–46.00]) versus HPV-negative cases (16.5 [12.00–24.25]); p<0.001) and normal controls (2.0 [1.00–3.00]). The count of atypical mitoses was significantly higher in HPV-positive tumors (15.5 [10.00–20.00]) compared to HPV-negative cases (p<0.001). The count of binucleated or multinucleated tumor cells was lower in HPV-independent carcinogenesis (4.0 [2.00–8.25]) compared to virus-associated tumors (24.5 [23.25–32.75]). HPV-associated mitotic figures were identified in 85.7% (n=18) of HPV-positive vulvar carcinoma samples. Conclusion. HPV infection results in abnormal mitoses and development of multinucleated malignant cells. HPV-driven tumors display pathognomonic aberrant mitoses with extrachromosomal chroma- tin fragments adjacent to the central spindle. HPV-associated tumors demonstrate enhanced radiosensitivity, likely due to their characteristic chromosomal instability and defective DNA repair mechanisms. Conclusion. HPV infection results in abnormal mitoses and development of multinucleated malignant cells. HPV-driven tumors display pathognomonic aberrant mitoses with extrachromosomal chromatin fragments adjacent to the central spindle. HPV-associated tumors demonstrate enhanced radiosensitivity, likely due to their characteristic chromosomal instability and defective DNA repair mechanisms.

Depleted uranium has high cumulative capacity and, upon entering the human body, exerts radiological and chemotoxic effects. The aim of the study was to immunohistochemically evaluate the activity of caspase-3 and -9, as well as the response of stromal mast cells in the parotid salivary gland at 1, 3, and 6 months after a single oral administration of an aqueous solution of depleted uranium oxides. Material and methods. The experiment was conducted on 180 outbred male white rats divided into 6 groups (3 experimental and 3 control). Animals in the experimental groups received a single oral dose of depleted uranium (0.01 mg/100 g body weight). The parotid glands of control and experimental groups were examined after 1, 3, and 6 months. Organs were fixed in 10% neutral formalin, followed by histological staining (hematoxylin-eosin), immunohisto- chemical detection of caspases-3 and -9, and identification of mast cells (tryptase⁺, ChAE⁺). Results. At 1 month after depleted uranium administration, ultrastructural changes in acinar cells (vacuolization, protein dystrophy) and stromal inflammatory reactions (edema, vascular congestion) were observed. Immunohistochemical analysis revealed a significant increase in caspase-9 activity in the parenchyma, while caspase-3 expression increased significantly only by the 3rd month. By the 6th month, caspase-induced apoptosis in the parenchyma decreased but persisted in ductal cells. Mast cells showed peak activity at 1 month (increased tryptase⁺ and ChAE⁺ cells), followed by a decline in functional activity by the 6th month. Conclusion. Oral intake of depleted uranium oxides induces a biphasic response in the parotid gland: an early phase (1 month) involves acute damage with activation of the mitochondrial apoptosis pathway (caspase-9) and mast cell degranulation, while a late phase (3–6 months) transitions to chronic inflammation with predominant caspase-3-dependent apoptosis in the ducts. These findings enhance the understanding of depleted uranium toxicity mechanisms, highlighting the role of stromal-parenchymal interactions in long-term salivary gland damage.

The aim of the study was to identify the phenotype of medial epiphyseal growth plate cells in the proximal tibia in Blount's disease. Material and methods. The study was conducted on medial epiphyseal growth plates of the proximal tibia in unilateral Blount's disease of stages III–IV. Cartilage tissue samples were obtained at the Pediatric Orthopedics Clinic of the Novosibirsk Research Institute of Traumatology and Orthopedics from 5 children (4 girls, 1 boy) aged 3 to 8 years. Growth plate cells were cultured up to passage 4 and analyzed using immunofluorescence microscopy for chondrogenic (Collagen II) and neural markers (Musashi-1, PAX6 , SOX2, NF200). Morphometric measurements were conducted with ImageJ software. Results. Two different cell phenotypes were observed in the proximal tibial growth plates of individuals with Blount's disease. Type 1: Chondrocytes exhibiting a differentiation gradient, with type II collagen positivity and absence of neural marker staining. Type 2: Cells displaying either bipolar or multipolar architecture, with multiple thin processes. Neural-phenotype cells showed positive expression of both early-stage markers (Musashi-1, PAX6, SOX2) and the mature neuronal marker NF200. The nuclear, cytoplasmic, and cellular areas, as well as nuclear-to- cytoplasmic ratios, showed statistically significant differences between the identified phenotypes. Conclusion. Neural lineage cells were detected in the dysregulated growth plate microenvironment of Blount's disease. We hypothesize that neural crest-derived cells may contribute to the pathogenesis of knee joint defects in this context.

This paper reviews modern literature on gingival anatomy and biotype assessment methods, with the goal of analyzing and systematizing the data. A literature search was performed in PubMed and Elibrary. ru (2005–2025) with the keywords: “gingival biotype”, “periodontal diseases” and “gingival biotype evaluation techniques”. From an initial pool of 258 sources, 90 original studies met the inclusion criteria and were selected for analysis. The gingiva is one of the most important structures of the periodontium, providing trophic, barrier, supportive, stabilizing, shock-absorbing, and sensory functions. As the only visible part of the periodontium that is readily accessible for examination, the gingiva’s morphofunctional status can serve as an indicator of the condition of other periodontal tissues. Gingival thickness is a key criterion of its biotype and significantly influences treatment outcomes for periodontal pathology and dental implantation. The gingiva is classified into two main biotypes (thick and thin), with some studies identifying an intermediate category. Each biotype exhibits distinct inflammatory responses and susceptibility to harmful agents and traumatic injuries. A thick gingival biotype demonstrates considerable keratinized tissue thickness (1,5–2 mm) with squat, wide papillae and subtle curvature of the gingival margin. Conversely, thin biotypes exhibit about 1 mm keratinized tissue, highly scalloped margins, slender tooth crowns, and tall, narrow papillae. The reported prevalence of gingival biotypes varies considerably across studies. The morphological characteristics of gingival tissue are critical for predicting outcomes in periodontal therapy and orthodontic treatment. Different gingival biotypes exhibit distinct responses to inflammation, exposure to aggressive agents, and mechanical trauma. Numerous assessment methods exist for evaluating gingival biotype, including direct measurement, transgingival probing, ultrasonography, periodontal probe transparency technique, cone-beam computed tomography, intraoral and extraoral ultrasonography, and intraoral digital scanning.

The article is devoted to the life and scientific work of N.K. Permyakov, an outstanding Russian pathologist, who significantly influenced the development of pathomorphology and forensic medicine in the country. Guided by his mentor Professor A.V. Rusakov, he cultivated a scientific school founded on the close cooperation of clinical practitioners and researchers. N.K. Permyakov meticulously investigated and documented the pathomorphological characteristics of various pathological states and resuscitation outcomes. He is credited with creating a classification system for resuscitation complications, organized according to different modalities of intensive therapy. In the course of his doctoral research entitled “General Purulent Infection After Abortion”, he additionally established a clinico-pathological classification of post-abortion sepsis. His contributions to the pathology of critical conditions maintain their significance today, being utilized by both anatomical pathologists and practicing physicians. N.K. Permyakov served in executive roles at two prestigious institutions: the N.V. Sklifosovsky Institute of Emergency Medicine and the Research Institute of Human Morphology under the Russian Academy of Medical Sciences. He was also head of the Pathology Department at I.M. Sechenov First Moscow Order of Lenin State Medical Institute. During his tenure at the Research Institute of Human Morphology, Nikolai Konstantinovich proved himself as a talented leader. A dedicated autopsy unit (prosectorium) was established at the institute – an essential facility for its full scientific and practical development. Additionally, the organization of practical training bases at other clinical centers enabled the institute to survive and continue its research despite the sharp decline in scientific funding at the end of the 20th century. The creation of the Pathological Anatomy Department at I.M. Sechenov Moscow Medical Academy's Postgraduate Medical Faculty represented a major milestone in developing Russia's cadre of highly skilled pathomorphology specialists. N.K. Permyakov made enduring contributions to pathological anatomy and remains an inspirational figure for future physicians through his unwavering commitment to scientific and educational excellence.

This article is devoted to the scientific and social activities of M.D., Professor, N.I. Odnoralov, the founder of one of the neuromorphological schools of the USSR in the second half of the twentieth century. The «scientific family tree» of Professor N.I. Odnoralov is shown; the results of scientific research together with students during the years of work at the Voronezh Medical Institute; as well as the results of scientific activity of his students – professors who headed the departments of anatomy and created their own scientific schools. For the first time, within the framework of one article, the results of scientific research by neuromorphologists – students of N.I. Odnoralov who worked in Chita, Smolensk, Kursk, Minsk and Vladikavkaz are presented. In general, the article introduces the «family tree» of one of the scientific anatomical schools of the twentieth century, and also allows you to trace the process of accumulation of knowledge in the field of neuromorphology in the second half of the twentieth century.

Science owes the discovery of nucleic acids to the Swiss scientist Johann Friedrich Miescher (1844–1895). In 1869, he discovered a new substance of unknown nature, containing nitrogen and phosphorus, in the cell nuclei of leukocytes, and named this substance nuclein. Then he discovered this substance in the nuclei of various cells, and also suggested their role and significance in cells. The study of nucleic acids started by chemists was continued by biologists and doctors. In the 19th and early 20th centuries, various aspects of the characteristics of nucleic acids were successfully studied by A. Kossel, A.N. Belozersky, A.N. Spirin, N.K. Koltsov, A. Todd, A. Claude, K. De Duve, D. Palade, E. Chargaff. Of outstanding importance for progress in the study of nucleic acids were the work on deciphering the structure of DNA (R. Franklin, D. Watson, F. Crick, M. Wilkins, A. Hershey, S. Luria, M. Delbruck), work on establishing the mechanism of protein synthesis (A.M. Lvov, F. Jacob, J.L. Monod), research on artificial synthesis DNA and RNA (H.G. Koran et al.) At the end of the twentieth century, based on the integration of molecular biology and genetics, a new direction in biology emerged – genetic engineering, whose tasks are to introduce foreign genes into the genome of cells in order for these cells to acquire new properties or to replace defective genes. On the basis of genetic engineering, gene therapy has emerged. Assisted reproductive technologies began to be introduced into the clinic. The field of genetic engineering has achieved great development, aimed at rearranging the bacterial genome in order to use them as sources of synthesis of many biologically active substances that are extremely necessary for humans.