Local Proliferation Research Articles

Filaments of ABS loaded with Neomycin – a supplier to produce surfaces by 3D printing

The skin of several animals can be affected by bacterial infection, especially in the case of dogs and cats. Among the bacteria that can cause skin and soft tissue infections, Staphylococcus aureus (S. aureus) is one of the commonest. Neomycin (NEO) is one of the most used antibiotics to prevent bacterial infections. Due to this cochleotoxicity and nephrotoxicity, their use is topical. Animals infected by these bacteria can potentially contaminate healthy animals and humans. A possible alternative may be the development of surfaces with bactericidal properties where animals, during the treatment phase, can rest without favoring the local proliferation of the bacteria. This work aims to produce, by hot extrusion, filaments of acrylonitrile butadiene styrene (ABS) with neomycin. ABS is a thermoplastic polymer commonly used in fused deposition modeling (FDM). A mixture of ABS and NEO (1:6% w/w) was extruded, resulting in ABS/neomycin filament with a diameter of 2.4 mm. Scanning electron microscopy (SEM), X-ray diffraction (XRD), and Fourier transform infrared spectrometry (FTIR) showed that the filament might be used for the production of surfaces by 3D printing.

Ets21C sustains a pro-regenerative transcriptional program in blastema cells of Drosophila imaginal discs

An important unanswered question in regenerative biology is to what extent regeneration is accomplished by the reactivation of gene regulatory networks used during development versus the activation of regeneration-specific transcriptional programs. Following damage, Drosophila imaginal discs, the larval precursors of adult structures, can regenerate missing portions by localized proliferation of damage-adjacent tissue. Using single-cell transcriptomics in regenerating wing discs, we have obtained a comprehensive view of the transcriptome of regenerating discs and identified two regeneration-specific cell populations within the blastema, Blastema1 and Blastema2. Collectively, these cells upregulate multiple genes encoding secreted proteins that promote regeneration including Pvf1, upd3, asperous, Mmp1, and the maturation delaying factor Ilp8. Expression of the transcription factor Ets21C is restricted to this regenerative secretory zone; it is not expressed in undamaged discs. Ets21C expression is activated by the JNK/AP-1 pathway, and it can function in a type 1 coherent feedforward loop with AP-1 to sustain expression of downstream genes. Without Ets21C function, the blastema cells fail to maintain the expression of a number of genes, which leads to premature differentiation and severely compromised regeneration. As Ets21C is dispensable for normal development, these observations indicate that Ets21C orchestrates a regeneration-specific gene regulatory network. We have also identified cells resembling both Blastema1 and Blastema2 in scribble tumorous discs. They express the Ets21C-dependent gene regulatory network, and eliminating Ets21C function reduces tumorous growth. Thus, mechanisms that function during regeneration can be co-opted by tumors to promote aberrant growth.

A 2-tier subdivision of papillary proliferations of the endometrium (PPE) only emphasizing the complexity of papillae precisely predicts the neoplastic risk and reflects the neoplasia-related molecular characteristics—a single-centered analysis of 207 cases

Papillary proliferation of the endometrium (PPE) is subdivided based on the complexity of the papillae and the proliferation of lesions, and the complex group is considered to have an increased risk of concurrent/subsequent endometrial neoplasia. However, the current subdivision criteria fail to prove the equivalence of the quantity of simple papillae and structural complexity. In this study, we divided PPE of 207 cases from 2014 to 2022 into 3 groups according to structural complexity and proliferation degrees: Group 1 equaled to the simple PPE with a simple papillary structure and typical localized proliferation; group 2 had the simple structure similar to group 1 but occupy over 50% of the endometrial polyp or > 2 lesions in the surface of nonpolypoid endometrium; group 3 had the truly complex branching papillae despite of its proportion. Group 3 was implicated with significantly more concurrent endometrial neoplasia (EAH and carcinoma) compared with groups 1 and 2 (P < 0.01), while no difference was found between groups 1 and 2. In 128 cases with no concurrent endometrial abnormalities in the initial biopsy or curettage specimens, 4 cases presented endometrial neoplasia (3 carcinoma and 1 atypical hyperplasia) in the subsequent specimens, all of which presented PPE of group 3 but not group 1 or 2 in the prior tissues (P < 0.01). The immunochemistry of 83 cases showed similar expressions of ER, PTEN, ARID1A, PTEN, p16, β-catenin, and p53 between PPE and the surrounding normal endometrium. Nearly 100% of PPE cases lost expressions of PR. A total of 2/83 cases showing PAX2 expression were all in the group 3 and correlated with endometrial neoplasia (2/17, 11.76%, P < 0.05). 76/83 (91.57%) of PPE lesions had KRAS mutations, and the distributions of which were similar among 3 groups. The frequency of mucinous metaplasia was significantly higher in the PPE lesions with KRAS mutations (72/74, 97.30%, P < 0.01). Group 3 showed higher frequency of single KRAS mutations compared with the combination of groups 1 and 2 (P < 0.01). Finally, the concordance of KRAS mutation profiles between PPE and endometrial neoplasia was significantly higher in group 3 than either group 1 or 2 (P < 0.01), while no difference was found between group 1 and 2. Thus, a new 2-tier subdivision system only emphasizing the complexity of papillae is recommended, which might precisely predict the risk of endometrial neoplasia and neoplasia-related molecular characteristics.

Epiblast inducers capture mouse trophectoderm stem cells invitro and pattern blastoids for implantation in utero.

The embryo instructs the allocation of cell states to spatially regulate functions. In the blastocyst, patterning of trophoblast (TR) cells ensures successful implantation and placental development. Here, we defined an optimal set of molecules secreted by the epiblast (inducers) that captures invitro stable, highly self-renewing mouse trophectoderm stem cells (TESCs) resembling the blastocyst stage. When exposed to suboptimal inducers, these stem cells fluctuate to form interconvertible subpopulations with reduced self-renewal and facilitated differentiation, resembling peri-implantation cells, known as TR stem cells (TSCs). TESCs have enhanced capacity to form blastoids that implant more efficiently in utero due to inducers maintaining not only local TR proliferation and self-renewal, but also WNT6/7B secretion that stimulates uterine decidualization. Overall, the epiblast maintains sustained growth and decidualization potential of abutting TR cells, while, as known, distancing imposed by the blastocyst cavity differentiates TR cells for uterus adhesion, thus patterning the essential functions of implantation.

Group 3 innate lymphocytes make a distinct contribution to type 17 immunity in bladder defence

SummaryBladder infection affects a hundred million people annually, but our understanding of bladder immunity is incomplete. We found type 17 immune response genes among the most up-regulated networks in mouse bladder following uropathogenic Escherichia coli (UPEC) challenge. Intravital imaging revealed submucosal Rorc+ cells responsive to UPEC challenge, and we found increased Il17 and IL22 transcripts in wild-type and Rag2−/− mice, implicating group 3 innate lymphoid cells (ILC3s) as a source of these cytokines. NCR-positive and negative ILC3 subsets were identified in murine and human bladders, with local proliferation increasing IL17-producing ILC3s post infection. ILC3s made a more limited contribution to bladder IL22, with prominent early induction of IL22 evident in Th17 cells. Single-cell RNA sequencing revealed bladder NCR-negative ILC3s as the source of IL17 and identified putative ILC3-myeloid cell interactions, including via lymphotoxin-β-LTBR. Altogether, our data provide important insights into the orchestration and execution of type 17 immunity in bladder defense.

Macrophage Fate Mapping.

Tissue‐resident macrophages are present in all tissues where they perform homeostatic and immune surveillance functions. In many tissues, resident macrophages develop from embryonic progenitors, which mature into a self‐maintaining population through local proliferation. However, tissue‐resident macrophages can be supported by recruited monocyte‐derived macrophages during scenarios such as tissue growth, infection, or sterile inflammation. Circulating blood monocytes arise from hematopoietic stem cell progenitors and possess unique gene profiles that support additional functions within the tissue. Determining cell origins (ontogeny) and cellular turnover within tissues has become important to understanding monocyte and macrophage contributions to tissue homeostasis and disease. Fate mapping, or lineage tracing, is a promising approach to tracking cells based on unique gene expression driving reporter systems, often downstream of a Cre‐recombinase–mediated excision event, to express a fluorescent protein. This approach is typically deployed temporally with developmental stage, disease onset, or in association with key stages of inflammation resolution. Importantly, myeloid fate mapping can be combined with many emerging technologies, including single‐cell RNA‐sequencing and spatial imaging. The application of myeloid cell fate mapping approaches has allowed for impactful discoveries regarding myeloid ontogeny, tissue residency, and monocyte fate within disease models. This protocol outline will discuss a variety of myeloid fate mapping approaches, including constitutive and inducible labeling approaches in adult and embryo tissues. This article outlines basic approaches and models used in mice for fate mapping macrophages. © 2022 The Authors. Current Protocols published by Wiley Periodicals LLC. Basic Protocol 1: Adult Fate Mapping Basic Protocol 2: Embryonic Fate Mapping

MITF in Normal Melanocytes, Cutaneous and Uveal Melanoma: A Delicate Balance.

Microphthalmia-associated transcription factor (MITF) is an important regulator of melanogenesis and melanocyte development. Although it has been studied extensively in cutaneous melanoma, the role of MITF in uveal melanoma (UM) has not been explored in much detail. We review the literature about the role of MITF in normal melanocytes, in cutaneous melanoma, and in UM. In normal melanocytes, MITF regulates melanocyte development, melanin synthesis, and melanocyte survival. The expression profile and the behaviour of MITF-expressing cells suggest that MITF promotes local proliferation and inhibits invasion, inflammation, and epithelial-to-mesenchymal (EMT) transition. Loss of MITF expression leads to increased invasion and inflammation and is more prevalent in malignant cells. Cutaneous melanoma cells switch between MITF-high and MITF-low states in different phases of tumour development. In UM, MITF loss is associated with loss of BAP1 protein expression, which is a marker of poor prognosis. These data indicate a dual role for MITF in benign and malignant melanocytic cells.

Intranasal administration of a recombinant RBD vaccine induces long-term immunity against Omicron-included SARS-CoV-2 variants

The outbreak of coronavirus disease 2019 (COVID-19) has posed great threats to global health and economy. Several effective vaccines are available now, but additional booster immunization is required to retain or increase the immune responses owing to waning immunity and the emergency of new variant strains. The deficiency of intramuscularly delivered vaccines to induce mucosal immunity urged the development of mucosal vaccines. Here, we developed an adjuvanted intranasal RBD vaccine and monitored its long-term immunogenicity against both wild-type and mutant strains of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2), including Omicron variants, in mice. Three-dose intranasal immunization with this vaccine induced and maintained high levels of neutralizing IgG antibodies in the sera for at least 1 year. Strong mucosal immunity was also provoked, including mucosal secretory IgA and lung-resident memory T cells (TRM). We also demonstrated that the long-term persistence of lung TRM cells is a consequence of local T-cell proliferation, rather than T-cell migration from lymph nodes. Our data suggested that the adjuvanted intranasal RBD vaccine is a promising vaccine candidate to establish robust, long-lasting, and broad protective immunity against SARS-CoV-2 both systemically and locally.

Mediastinal Lymphohemangioma (Case Report): A (Report of a) Rare Case with Difficult Diagnosis

Mediastinal lymphohemangioma is a very rare, benign, congenital malformation. Mediastinal lymphohemangioma originates from local proliferation of lymphatic vessels. This disorder is accountable for 4.5% among all mediastinal tumors. Most lymphohemangiomas are found in the neck and axillary region among children, whereas only 1% are found in the mediastinum and tend to occur in individuals aged over 20 years old. A proper understanding is needed to be able to make a diagnosis and perform effective management of mediastinal lymphohemangiomaIn this case report, a woman with a diagnosis of mediastinal lymphohemangioma, established through a multidisciplinary approach covering the fields of pulmonology, thoracic and cardiovascular surgery, radiology, and anatomical pathology.Keywords: Mediastinal Lymphohemangioma, Core Biopsy, Thoracotomy

Restricted Proliferation During Neurogenesis Contributes to Regionalisation of the Amphioxus Nervous System.

The central nervous system of the cephalochordate amphioxus consists of a dorsal neural tube with an anterior brain. Two decades of gene expression analyses in developing amphioxus embryos have shown that, despite apparent morphological simplicity, the amphioxus neural tube is highly regionalised at the molecular level. However, little is known about the morphogenetic mechanisms regulating the spatiotemporal emergence of cell types at distinct sites of the neural axis and how their arrangements contribute to the overall neural architecture. In vertebrates, proliferation is key to provide appropriate cell numbers of specific types to particular areas of the nervous system as development proceeds, but in amphioxus proliferation has never been studied at this level of detail, nor in the specific context of neurogenesis. Here, we describe the dynamics of cell division during the formation of the central nervous system in amphioxus embryos, and identify specific regions of the nervous system that depend on proliferation of neuronal precursors at precise time-points for their maturation. By labelling proliferating cells in vivo at specific time points in development, and inhibiting cell division during neurulation, we demonstrate that localised proliferation in the anterior cerebral vesicle is required to establish the full cell type repertoire of the frontal eye complex and the putative hypothalamic region of the amphioxus brain, while posterior proliferating progenitors, which were found here to derive from the dorsal lip of the blastopore, contribute to elongation of the caudal floor plate. Between these proliferative domains, we find that trunk nervous system differentiation is independent from cell division, in which proliferation decreases during neurulation and resumes at the early larval stage. Taken together, our results highlight the importance of proliferation as a tightly controlled mechanism for shaping and regionalising the amphioxus neural axis during development, by addition of new cells fated to particular types, or by influencing tissue geometry.

Single-cell RNA sequencing of mast cells in eosinophilic esophagitis reveals heterogeneity, local proliferation, and activation that persists in remission

Mast cells (MCs) are pleiotropic cells that accumulate in the esophagus of patients with eosinophilic esophagitis (EoE) and are thought to contribute to disease pathogenesis, yet their properties and functions in this organ are largely unknown. This study aimed to perform a comprehensive molecular and spatial characterization of esophageal MCs in EoE. Esophageal biopsies obtained from patients with active EoE, patients with EoE in histologic remission, and individuals with histologically normal esophageal biopsies and no history of esophageal disease (ie, control individuals) were subject to single-cell RNA sequencing, flow cytometry, and immunofluorescence analyses. This study probed 39,562 single esophageal cells by single-cell RNA sequencing; approximately 5% of these cells were MCs. Dynamic MC expansion was identified across disease states. During homeostasis, TPSAB1highAREGhigh resident MCs were mainly detected in the lamina propria and exhibited a quiescent phenotype. In patients with active EoE, resident MCs assumed an activated phenotype, and 2 additional proinflammatory MC populations emerged in the intraepithelial compartment, each linked to a proliferating MKI67high cluster. One proinflammatory activated MC population, marked as KIThighIL1RL1highFCER1Alow, was not detected in disease remission (termed "transient MC"), whereas the other population, marked as CMA1highCTSGhigh, was detected in disease remission where it maintained an activated state (termed "persistent MC"). MCs were prominent producers of esophageal IL-13 mRNA and protein, a key therapeutic target in EoE. Esophageal MCs comprise heterogeneous populations with transcriptional signatures associated with distinct spatial compartmentalization and EoE disease status. In active EoE, they assume a proinflammatory state and locally proliferate, and they remain activated and poised to reinitiate inflammation even during disease remission.

Spatial and Temporal Patterns of Symbiont Colonization and Loss During Bleaching in the Model Sea Anemone Aiptasia

The ability of symbionts to recolonize their hosts after a period of dysbiosis is essential to maintain a resilient partnership. Many cnidarians rely on photosynthate provided from a large algal symbiont population. Under periods of thermal stress, symbiont densities in host cnidarians decline, and the recovery of hosts is dependent on the re-establishment of symbiosis. The cellular mechanisms that govern this process of colonization are not well-defined and require further exploration. To study this process in the symbiotic sea anemone model Exaiptasia diaphana, commonly called Aiptasia, we developed a non-invasive, efficient method of imaging that uses autofluorescence to measure the abundance of symbiont cells, which were spatially distributed into distinct cell clusters within the gastrodermis of host tentacles. We estimated cell cluster sizes to measure the occurrence of singlets, doublets, and so on up to much larger cell clusters, and characterized colonization patterns by native and non-native symbionts. Native symbiont Breviolum minutum rapidly recolonized hosts and rapidly exited under elevated temperature, with increased bleaching susceptibility for larger symbiont clusters. In contrast, populations of non-native symbionts Symbiodinium microadriaticum and Durusdinium trenchii persisted at low levels under elevated temperature. To identify mechanisms driving colonization patterns, we simulated symbiont population changes through time and determined that migration was necessary to create observed patterns (i.e., egression of symbionts from larger clusters to establish new clusters). Our results support a mechanism where symbionts repopulate hosts in a predictable cluster pattern, and provide novel evidence that colonization requires both localized proliferation and continuous migration.

Understanding complex spatial dynamics from mechanistic models through spatio‐temporal point processes

Landscape heterogeneity affects population dynamics, which determine species persistence, diversity and interactions. These relationships can be accurately represented by advanced spatially‐explicit models (SEMs) allowing for high levels of detail and precision. However, such approaches are characterised by high computational complexity, high amount of data and memory requirements and spatio‐temporal outputs may be difficult to analyse. A possibility to deal with this complexity is to aggregate outputs over time or space, but then interesting information may be masked and lost, such as local spatio‐temporal relationships or patterns. An alternative solution is given by meta‐models and meta‐analysis, where simplified mathematical relationships are used to structure and summarise the complex transformations from inputs to outputs. Here, we propose an original approach to analyse SEM outputs. By developing a meta‐modelling approach based on spatio‐temporal point processes (STPPs), we characterise spatio‐temporal population dynamics and landscape heterogeneity relationships in agricultural contexts. A landscape generator and a spatially‐explicit population model simulate hierarchically the pest–predator dynamics of codling moth and ground beetles in apple orchards over heterogeneous agricultural landscapes. Spatio‐temporally explicit outputs are simplified to marked point patterns of key events, such as local proliferation or introduction events. Then, we construct and estimate regression equations for multi‐type STPPs composed of event occurrence intensity and magnitudes. Results provide local insights into spatio‐temporal dynamics of pest–predator systems. We are able to differentiate the contributions of different driver categories (i.e. spatio‐temporal, spatial, population dynamics). We highlight changes in the effects on occurrence intensity and magnitude when considering drivers at global or local scale. This approach leads to novel findings in agroecology where, for example, we show that the organisation of cultivated patches and semi‐natural elements play different roles for pest regulation depending on the scale considered. It aids to formulate guidelines for biological control strategies at global and local scale.

The effect of intrinsic instability on the surface topography of spherical 2-acetylfuran flame

The intrinsic instability of 2-acetylfuran (2-AF) expanding flame has been investigated at initial temperatures of 453–493 K, pressures of 1–3 bar, and equivalence ratios of 0.8–1.4. The linear stability theory was used to analyze the influence of the initial temperatures, initial pressures, and equivalence ratios on the 2-AF flame intrinsic instability. Moreover, an image processing technique was applied to obtain the experimental cell-wavenumber from the topography of 2-AF cellular flame to quantitatively analyze the local cell proliferation. The topography of the 2-AF expanding flame shows that the initial pressures and equivalence ratios are the two influential factors to its intrinsic instability. More specifically, the higher the initial pressures, as well as the equivalence ratios, the earlier the time of the flame becomes unstable. Furthermore, according to the comparison between the local experimental and theoretical wavenumbers, it is found that the average local experimental wavenumber falls within the unstable zone predicted by the linear stability theory. Last but not least, the cell-wavenumber distribution in the different regions on the 2-AF expanding flame surface indicates that the initial crack has a weaker shaping effect on the flame surface than the formation of small spontaneous cells.

Spiny pollen-based antigen-presenting clusters for promoting T cells expansion

Adoptive T cell immunotherapy is a powerful strategy for clinical cancer treatment. As a critical step to generate clinical-grade T cell products for therapeutic applications, novel approaches for T cell activation and expansion attract increasing attention. Here, we develop hydrogel-integrated natural pollens as artificial antigen-presenting scaffolds for ex vivo T cell expansion. Black phosphorus is presented in the scaffolds that allow for NIR-triggered release of cytokines and antibodies for T cell activation. Besides, the distinctive spike structure and high surface area of pollens contribute to T cell cluster formation and enhance their local proliferation. After ex vivo expansion, the activated T cells exhibit robust antitumor activity. Therefore, these features demonstrate that the novel pollen-based antigen-presenting scaffolds are promising for therapeutic T cell preparation.

Chronic kidney disease mediates cardiac dysfunction associated with increased resident cardiac macrophages

BackgroundThe leading cause of death in end-stage kidney disease is related to cardiovascular disease. Macrophages are known to be involved in both chronic kidney disease (CKD) and heart failure, however their role in the development of cardiorenal syndrome is less clear. We thus sought to investigate the role of macrophages in uremic cardiac disease.MethodsWe assessed cardiac response in two experimental models of CKD and tested macrophage and chemokine implication in monocytopenic CCR2−/− and anti-CXCL10 treated mice. We quantified CXCL10 in human CKD plasma and tested the response of human iPSC-derived cardiomyocytes and primary cardiac fibroblasts to serum from CKD donors.ResultsWe found that reduced kidney function resulted in the expansion of cardiac macrophages, in particular through local proliferation of resident populations. Influx of circulating monocytes contributed to this increase. We identified CXCL10 as a crucial factor for cardiac macrophage expansion in uremic disease. In humans, we found increased plasma CXCL10 concentrations in advanced CKD, and identified the production of CXCL10 in cardiomyocytes and cardiac fibroblasts.ConclusionsThis study provides new insight into the role of the innate immune system in uremic cardiomyopathy.

Decrease of CD38 expression is linked to increase of solitary plasmacytoma pathological grade: a single institution experience from China.

Solitary plasmacytoma (SP) is a rare plasma cell disorder characterized by localized neoplastic proliferation of monoclonal plasma cell. Due to its rarity, further understanding of the spectrum of its clinicopathologic features is needed. A retrospective analysis of cases from a single institution was conducted. Clinical characteristics of the patients were collected; histopathological and semi-quantitative immunohistochemical analyses were performed. Thirteen cases were identified from our pathology archives, including 4 cases of solitary plasmacytoma of bone (SPB) (30.8%) and 9 extraosseous plasmacytoma (EP) (69.2%). The mean age of EP is a decade older than SPB. There is no gender disparity. The most common sites involved are the vertebrae and nasopharynx. Histologically, the tumors can be classified into two grades based on degree of differentiation. Immunohistochemically the tumor cells express CD38, CD138, MUM-1, and exhibit light chain restriction. Ki-67 proliferation index is 30%. In situ hybridization for Epstein-Barr virus-encoded small RNAs (EBER) is negative in six cases tested. Semi-quantitative immunohistochemical analysis showed decreased integrated optical density (IOD) of CD38 in neoplastic cells. IgH gene rearrangement was identified in two cases. SP is a rare plasmacytoid neoplasm that occurs more frequently in older patients. Diagnosis requires a systematic clinical approach combined with the pathological characteristics of plasmacytoid morphology, immunophenotype and light chain restriction. There are more cases of EP than SPB in our series, which is in contrast to that reported in literature. Results from this study suggest that CD38 is a potential immunohistochemical marker associated with prognosis of SP. Further studies with more cases and longer term follow-up may provide more definitive information on risk of progression from SP to multiple myeloma (MM).

Combination of Anlotinib and Celecoxib for the Treatment of Abdominal Desmoid Tumor: A Case Report and Literature Review

Desmoid tumor is a rare disease, which is histologically characterized by local invasion, monoclonality, and fibroblast proliferation; and clinically characterized by a variable and often unpredictable course. The treatment of desmoid tumor is mainly surgical resection, but the recurrence rate is high. In recent years, a variety of treatment methods, including endocrine therapy, surgery, radiotherapy, chemotherapy, non-steroidal anti-inflammatory drugs, targeted drugs, interferon and more, have been used and achieved certain curative effects. In addition, in view of the inertia characteristics of desmoid tumor, observation is also a first-line scheme recommended by multiple guidelines. In the past, the research progress of targeted therapy for desmoid tumor is relatively slow and the curative effect is limited. Thus, targeted therapy is usually used as a remedial treatment after the failure of other conventional treatment methods. However, in recent years, with the rapid progress in the basic research of targeted therapy, some new targeted drugs are increasingly used for the clinical treatment of desmoid tumor and have achieved good results. Herein, we described a patient with aggressive fibromatosis in the abdominal cavity. Following a combined treatment using anlotinib and celecoxib, the patient achieved a partial response with mild toxicity. Simultaneously, the patient’s pain symptoms completely disappeared. This case indicates that the combination of anlotinib and NSAIDs could be an effective treatment for desmoid tumor.

Современные представления о роли гематоэнцефалического барьера в развитии лимфом центральной нервной системы

The review summarizes modern researches about the role of the blood-brain barrier (BBB) in the development of lymphomas of the central nervous system (CNS). Currently, it has been established that the BBB is a highly active structure. On the one hand, it protects the brain tissue from chemical, physical and other influences, and on the other hand, it is uniquely adapted for transmitting signals between the CNS and other parts of the body. BBB cells respond to signals from the CNS or blood compartments that can stimulate changes in their barrier, transport, and secretory functions. The immune privilege of the CNS is not absolute. Normally, extravasation of lymphocytes through the BBB is crucial for immune surveillance in nervous tissue, although it is tightly regulated. Damage to the BBB is one of the central links in the pathogenesis of many diseases of the nervous system, and the nonspecific permeability of the BBB can increase significantly in various somatic pathologies. In general, immunological dysfunction and inflammation are the main factors in the violation of the BBB integrity. The mechanisms of metastasis of malignant lymphomas in the CNS remain poorly understood, although it is already clear that their implementation requires interactions between circulating tumor cells and BBB components, while some cytokines can act as attractants for metastatic cells, and the process of tumor development includes several stages from extravasation to local proliferation and activation of neoangiogenesis.

Medullary Solitary Plasmacytoma of Maxilla- A Rare Case Report

Solitary Plasmacytoma (SP) is a rare disease characterized by a localized proliferation of neoplastic monoclonal plasma cells, without evidence of systemic disease. The aetiology of SP remains unknown, but chronic stimulation, overdose irradiation, viruses, and gene interactions in the reticuloendothelial system have been suggested as the etiologic factor. While pain is the most common symptom of osseous mandible SP, it is usually painless in the maxilla and may manifest orally with paresthesia, swelling, soft tissue masses, mobility and migration of teeth, haemorrhage, or pathologic fracture due to cortical destruction of bone. Because the amount of haemopoitic bone marrow in the maxilla is decreased, oral involvement of the maxilla is less common than that of the mandible. A 46-year-old male patient presented with the chief complaint of mobility of his upper left back teeth and swelling over his left-side palatal area. Clinical examination was suggestive of benign odontogenic tumors and salivary gland tumors, while two-dimensional (2D) and three-dimensional (3D) imaging were suggestive of malignant tumors arising from either alveolar bone or maxillary sinus. The laboratory investigations and biopsy revealed solitary plasmacytoma of maxilla. There were clinical symptoms of paresthesia and mobility, but no other signs of malignancy were observed. As the case report concludes, all necessary investigations need to be conducted to exclude all other pathologies, so that treatment can begin as soon as possible.