Bacterial protein domains with a novel Ig-like fold target human CEACAM receptors.

Streptococcus agalactiae, also known as group B Streptococcus (GBS), is the major cause of neonatal sepsis in humans. A critical step to infection is adhesion of bacteria to epithelial surfaces. GBS adhesins have been identified to bind extracellular matrix components and cellular receptors. However, several putative adhesins have no host binding partner characterised. We report here that surface-expressed ß protein of GBS binds to human CEACAM1 and CEACAM5 receptors. A crystal structure of the complex showed that an IgSF domain in ß represents a novel Ig-fold subtype called IgI3, in which unique features allow binding to CEACAM1. Bioinformatic assessment revealed that this newly identified IgI3 fold is not exclusively present in GBS but is predicted to be present in adhesins from other clinically important human pathogens. In agreement with this prediction, we found that CEACAM1 binds to an IgI3 domain found in an adhesin from a different streptococcal species. Overall, our results indicate that the IgI3 fold could provide a broadly applied mechanism for bacteria to target CEACAMs.

Rare non-serous fallopian tube cancers: institutional experience and literature review.

INTRODUCTION: We reviewed 63 reports from the literature on rare non-serous tumors of the fallopian tubes and carried out a comparative analysis of clinical manifestations and diagnostic methods. We also report our observations from patients with these tumors. MATERIALS AND METHODS: Of 157 patients with primary fallopian tube cancer (FTC) treated in our regional oncological hospital between 1970 and 2020, there were nine (6%) cases of rare non-serous cancers, including one case each of choriocarcinoma, carcinosarcoma, and neuroendocrine tumor, and two cases each of non-keratinizing squamous cell carcinoma, mucinous adenocarcinoma, and clear cell adenocarcinoma. RESULTS: For carcinosarcoma and squamous cell, clear cell, and transitional cell carcinomas, clinical history, patient age, and clinical manifestations were similar to the main group of FTCs. Choriocarcinoma differed significantly from other cancers of the fallopian tubes in terms of patient age and clinical course. Mucinous adenocarcinoma, mesothelioma, and borderline tumors, with rare exceptions, were almost always asymptomatic and were found only incidentally during surgery. Choriocarcinoma and carcinosarcoma had an aggressive course, while squamous cell, transitional cell, clear cell, and mucinous carcinomas were less aggressive. Since most rare non-serous tumors have a similar disease course to typical FTCs and there is a lack of appropriate treatment protocols for rare tumors, treatment options developed for ovarian tumors and FTC are justified for these tumors. CONCLUSION: Rare non-serous malignant fallopian tube tumors are very similar to serous and endometrioid FTC in terms of clinical manifestations and diagnosis.

Detection of melanin in the rat skin.

Melanogenesis disorder is called dyschromia, is involved in various conditions including vitiligo, solar lentigo, and melanoma, the last of which is the most malignant type of skin cancer. AIM: The aim of study was focused on histological visualization of melanogenic system. MATERIALS AND METHODS: To investigate the roles of melanocytes and melanin, we used a rat skin as an experimental animal. Samples were stained using hematoxylin-eosin, the Schmorl's technique, the Fontana-Masson technique, the Warthin-Starry technique, and the S100 immunohistochemistry marker technique. Microscopy images were analyzed using the ImageJ free software protocol. RESULTS: We found Fontana-Masson staining to be the most suitable for obtaining reliable results compared with the other methods, which had more disadvantages. We also found the S100 marker staining to be an effective tool for measuring the melanocyte count. CONCLUSIONS: We consider the ImageJ processing protocol and staining procedures to be useful tools to estimate melanin and melanocyte pathology.

Morphological features of the rat uterus.

The rat uterus is an important female reproductive organ that has essential for the organism's reproduction. That is why it is necessary to understand all the rat uterus' morphological features as a perfect biomodel for studying the molecular peculiarities of the female reproductive system and pathologies development in experimental studies. AIM: The aim of research was to perform the comprehensive morphological analysis of the uterine in intact female rats. MATERIALS AND METHODS: The uterine of reproductive-aged intact female rats were used in this research. The cytological study of vaginal smears, histological (H and E), and immunohistochemical (estrogen, progesterone, and Ki-67 receptors) analysis of uterus tissues were used for light microscopic examination. RESULTS: The rat's vaginal smears' cytological features showed a specific qualitative cellular composition (variation of leukocytes, nucleated and anucleated cornified epithelial cells) in different estrous cycle phases (proestrus, estrus, metestrus, and diestrus). Uterine histology showed the structural regularities of parenchymal and stromal components with clear differentiation on the endometrium, myometrium and perimetrium. It was presented uterus sensitivity to the influence of the sex hormones (positive to estrogen and progesterone receptors) and the variable cellular proliferation activity (Ki-67 expression) in the organ wall. CONCLUSIONS: Our research demonstrated that the rats« uterus has a unique structural organization, sex hormones sensitivity, and variable proliferation in the parenchymal and stromal components. The rat estrous cycle should be considered while studying the morphological features of the uterus. The rat's uterus may serve as an acceptable object for modeling various pathological processes with the following results' extrapolation.

Morphofunctional features of articular cartilage structure.

BACKGROUND: Articular cartilage is highly-organized nonvascularized tissue which is responsible in humans for pressure absorption under load, as well as for the smoothness of the opposite tangential bone surfaces. The purpose of our research is to study structural and functional features of articular cartilage at light- optical level by using state-of-the-art research methods of bone-cartilage tissue. MATERIAL AND METHODS: the study was conducted on samples of femoral heads. Hyper fine sections were subject to hematoxylin and eosin, Van Gieson's and PAS staining. In order to identify the receptor profile of chondrocytes and the features of protein arrangement in extracellular matrix we undertook an immunohistochemical study. RESULTS: An articular cartilage is quite organized tissue. As any other organ, it has parenchyma and stroma. Parenchyma is represented by one type of cells - chondrocytes, which, depending on how deep they are located in cartilage, have a different shape, size and functional features. The chondrocytes and extracellular matrix have different degrees of receptors expression. CONCLUSIONS: the cartilage is being constantly self-renewed, what is manifested by means of a rather slow division of the surface-located chondrocytes and programmed death of dystrophic-modi ed cells. The features of extracellular matrix structure determine the originality of cell location in different areas of cartilage tissue. Due to synthesis of specific proteins, chondrocytes self-regulate properties of cartilage tissue.

Primary cancer of the fallopian tubes: histological and immunohistochemical features.

The rare occurrence of the fallopian tubes cancer allows to assert that the experience of even a small number of observations has a undoubted scientific and practical interest. Nowadays this type of neoplasia occurs more o en in practical oncogynecology and is the primary source of serous ovarian and peritoneal tumors. The determination of tissue receptor status of primary fallopian tube cancer (ER, PR, Ki-67, HER2 / neu) will verify the degree of biological malignancy and predict the course of disease and suggest appropriate methods of treatment.

Histological and immunohistochemical features of medullary breast cancer.

Disputes take place among many scientists about the position of MC in the classification of breast cancer. Some say that this kind of tumor is a sign of invasive ductal carcinoma (IDC). Instead, most of modern researchers distinguish MC of the breast as a separate nosological unit. Primarily there were selected 20 cases of MC and 10 cases of IDC (as control group). The immunohistochemical study revealed the presence of ER, PR, HER2/neo, p53, Ki-67, MMP1 and E-cadherin receptors. In the study of receptor status of tumors it was observed that 100% of MC cases were estrogen-, progesterone- and HER2/ neu negative. The status of tumors on receptor p53 and Ki-67 was as follows: p53+ status had 80% and Ki-67+ had 85% of tissues of MC. In 75% of cases MC cells expressed marker of adhesion and in 100% of cases cells were receptor-negative for expression of MMP1. The data of the study show that the invasive ductal carcinoma and medullary carcinoma are completely independent and different types of malignancy in the breast. The favorable behavior of medullary cancer is associated with expression of E-cadherin receptors, which are essentially adhesion factor and absence of MMP1 which are factors of metastatic potential of the tumor.

Fluorescence visualization for cancer DETECTION: EXPERIENCE and perspectives.

The current review focuses on the latest advances in the improvement and application of fluorescence imaging technology. Near-infrared (NIR) fluorescence imaging is a promising new technique that uses non-specific fluorescent agents and targeted fluorescent tracers combined with a dedicated camera to better navigate and visualize tumors. Fluorescence-guided surgery (FGS) is used to perform various tasks, helping the surgeon to distinguish lymphatic vessels and nodes from surrounding tissues easily and quickly assess the perfusion of the planned resection area, including intraoperative visualization of metastases. The results of the insertion of fluorescence visualization as an auxiliary method to cancer detection and high-risk metastatic lesions in clinical practice have demonstrated enthusiastic results and huge potential. However, intraoperative fluorescence visualization must not be considered as a main diagnostic or treatment method but as an aid to the surgeon. Thus, fluorescence study does not dispense the diagnostic gold standards of benign or malignant tumors (conventional examination, biopsy, ultrasonography and computed tomography, etc.) and can be done usually during intraoperative treatment. Moreover, as fluorescence surgery and fluorescence diagnostic techniques continue to improve, it is likely that they will evolve towards targeted fluorescence imaging probes that will increasingly target a specific type of cancer cell. The most important point remains the search for highly selective messengers of fluorescent labels, which make it possible to identify tumor cells exclusively in the affected organs and indicate to surgeons the boundaries of their spread and metastasis.

Fallopian Tube Hemangioma Discovered on Follow-up for Uterine Leiomyoma.

Hemangioma in female reproductive organs, particularly in the fallopian tube (FT), is a sporadic disease. In this report, we describe a case of hidden capillary hemangioma in FT in a 39-year-old woman who suffered from uterine leiomyoma. During the preoperative stage, pelvic sonography, computed tomography, and diagnostic laparoscopy revealed a subserous leiomyomatous nodule located along the posterior wall of the uterus. Despite this, intraoperatively, a benign vascular neoplasm was diagnosed. Histologically, it is characterized by multiple thin-walled vascular spaces lined with a single layer of endothelial cells, in which single mitoses were observed. The diagnosis was then confirmed immunohistochemically by CD31 and CD34 expression in the endothelial cells lining the inner surface of the spaces and the low mitotic activity of the tumor cells. It is virtually impossible to diagnose this asymptomatic neoplasm before and during surgery, which can result in an inadequate number of surgeries. Incorrect interpretation of a benign tumor at a young age can lead to unnecessary radical surgery with a resulting loss of fertility, and an unrevealed malignant process can threaten life.

MXene-Polydopamine-antiCEACAM1 Antibody Complex as a Strategy for Targeted Ablation of Melanoma.

Photothermal therapy (PTT) is a method for eradicating tumor tissues through the use of photothermal materials and photosensitizing agents that absorb light energy from laser sources and convert it into heat, which selectively targets and destroys cancer cells while sparing healthy tissue. MXenes have been intensively investigated as photosensitizing agents for PTT. However, achieving the selectivity of MXenes to the tumor cells remains a challenge. Specific antibodies (Ab) against tumor antigens can achieve homing of the photosensitizing agents toward tumor cells, but their immobilization on MXene received little attention. Here, we offer a strategy for the selective ablation of melanoma cells using MXene-polydopamine-antiCEACAM1 Ab complexes. We coated Ti3C2Tx MXene with polydopamine (PDA), a natural compound that attaches Ab to the MXene surface, followed by conjugation with an anti-CEACAM1 Ab. Our experiments confirm the biocompatibility of the Ti3C2Tx-PDA and Ti3C2Tx-PDA-antiCEACAM1 Ab complexes across various cell types. We also established a protocol for the selective ablation of CEACAM1-positive melanoma cells using near-infrared irradiation. The obtained complexes exhibit high selectivity and efficiency in targeting and eliminating CEACAM1-positive melanoma cells while sparing CEACAM1-negative cells. These results demonstrate the potential of MXene-PDA-Ab complexes for cancer therapy. They underline the critical role of targeted therapies in oncology, offering a promising avenue for the precise and safe treatment of melanoma and possibly other cancers characterized by specific biomarkers. Future research will aim to refine these complexes for clinical use, paving the way for new strategies for cancer treatment.

Antioxidant, anti-inflammatory and epigenetic potential of curcumin in Alzheimer's disease.

Alzheimer's disease (AD) constitutes a multifactorial neurodegenerative pathology characterized by cognitive deterioration, personality alterations, and behavioral shifts. The ongoing brain impairment process poses significant challenges for therapeutic interventions due to activating multiple neurotoxic pathways. Current pharmacological interventions have shown limited efficacy and are associated with significant side effects. Approaches focusing on the early interference with disease pathways, before activation of broad neurotoxic processes, could be promising to slow down symptomatic progression of the disease. Curcumin-an integral component of traditional medicine in numerous cultures worldwide-has garnered interest as a promising AD treatment. Current research indicates that curcumin may exhibit therapeutic potential in neurodegenerative pathologies, attributed to its potent anti-inflammatory and antioxidant properties. Additionally, curcumin and its derivatives have demonstrated an ability to modulate cellular pathways via epigenetic mechanisms. This article aims to raise awareness of the neuroprotective properties of curcuminoids that could provide therapeutic benefits in AD. The paper provides a comprehensive overview of the neuroprotective efficacy of curcumin against signaling pathways that could be involved in AD and summarizes recent evidence of the biological efficiency of curcumins in vivo.

CEACAM expression in an in-vitro prostatitis model.

Background: Prostatitis is an inflammatory disease of the prostate gland, which affects 2-16% of men worldwide and thought to be a cause for prostate cancer (PCa) development. Carcinoembryogenic antigen-related cell adhesion molecules (CEACAMs) are deregulated in inflammation and in PCa. The role of CEACAMs in prostate inflammation and their possible contribution to the malignant transformation of prostate epithelial cells is still elusive. In this study, we investigated the expression of CEACAMs in an in-vitro prostatitis model and their potential role in malignant transformation of prostate epithelial cells. Methods: Normal prostate epithelial RWPE-1 cells were treated with pro-inflammatory cytokines to achieve an inflammatory state of the cells. The expression of CEACAMs and their related isoforms were analyzed. Additionally, the expression levels of selected CEACAMs were correlated with the expression of malignancy markers and the migratory properties of the cells. Results: This study demonstrates that the pro-inflammatory cytokines, tumor necrosis factor alpha (TNFα) and interferon-gamma (IFNγ), induce synergistically an up-regulation of CEACAM1 expression in RWPE-1 cells, specifically favoring the CEACAM1-L isoform. Furthermore, overexpressed CEACAM1-L is associated with the deregulated expression of JAK/STAT, NFκB, and epithelial-mesenchymal transition (EMT) genes, as well as an increased cell migration. Conclusion: We postulate that CEACAM1 isoform CEACAM1-4L may synergistically contribute to inflammation-induced oncogenesis in the prostate.

Metal ions doping effect on the physicochemical, antimicrobial, and wound healing profiles of alginate-based composite.

The alginate (Alg) matrix with immobilized hydroxyapatite (HAp) and zinc oxide (ZnO), cross-linked by chitosan (CS) and metal ions (Men+) Ca2+, Zn2+, and Cu2+ was created as a wound dressing. The effect of Men+ and their concentrations on water vapor transition, fluid handling, dehydration, drug release, and healing are shown. Me-containing samples have a lower sorption capacity, than a commercial Kaltostat, however, a much lower degree of their dehydration provides a longer wound wet. The Men+ presence lowers the environmental pH to slightly acidic values promoting healing. Ca2+, Zn2+, and Cu2+ in complexes with CS increase antimicrobial effect against E. coli and S. aureus, slow down the Anaesthesine release, making it compatible with Fickian diffusion in the Zn2+ and Cu2+ presence, and non-Fickian transport under Ca2+ influence. The material promotes the proliferation of the fibroblasts, an increase of collagen fibres, and new arterial and venous capillaries, indicating the intensity of the healing process.

Lung Metastases to the Heart with Atypical Clinical Manifestations of Cardiac Failure.

The heart is a rare site of cancer metastases, even from the most common malignancies, such as lung cancer. Cardiac metastases may lead to myocardial dysfunction. This report presents a case of lung cancer metastases to the left ventricular myocardium that clinically manifested as atypical symptoms of cardiac dysfunction. The metastases were not revealed until after the patient died. Posthumously, the anamnesis, autopsy results, and morphological examination were evaluated. We demonstrated that the atypical symptoms of cardiac dysfunction were caused by occult (undiagnosed) metastases of lung cancer cells to the heart. The doctors did not consider this variant as possible metastatic lung cancer, because the patient had been treated radically one year earlier.

In Vivo Safety of New Coating for Biodegradable Magnesium Implants.

Biodegradable Magnesium (Mg) implants are promising alternatives to permanent metallic prosthesis. To improve the biocompatibility and with the aim of degradation control, we provided Plasma Electrolytic Oxidation (PEO) of pure Mg implant in silicate-based solution with NaOH (S1 250 V) and Ca(OH)2 (S2 300 V). Despite the well-structured surface, S1 250 V implants induced enormous innate immunity reaction with the prevalence of neutrophils (MPO+) and M1-macrophages (CD68+), causing secondary alteration and massive necrosis in the peri-implant area in a week. This reaction was also accompanied by systemic changes in visceral organs affecting animals' survival after seven days of the experiment. In contrast, S2 300 V implantation was associated with focal lymphohistiocytic infiltration and granulation tissue formation, defining a more favorable outcome. This reaction was associated with the prevalence of M2-macrophages (CD163+) and high density of αSMA+ myofibroblasts, implying a resolution of inflammation and effective tissue repair at the site of the implantation. At 30 days, no remnants of S2 300 V implants were found, suggesting complete resorption with minor histological changes in peri-implant tissues. In conclusion, Ca(OH)2-contained silicate-based solution allows generating biocompatible coating reducing toxicity and immunogenicity with appropriate degradation properties that make it a promising candidate for medical applications.

Human CEACAM1 is targeted by a Streptococcus pyogenes adhesin implicated in puerperal sepsis pathogenesis.

Life-threatening bacterial infections in women after childbirth, known as puerperal sepsis, resulted in classical epidemics and remain a global health problem. While outbreaks of puerperal sepsis have been ascribed to Streptococcus pyogenes, little is known about disease mechanisms. Here, we show that the bacterial R28 protein, which is epidemiologically associated with outbreaks of puerperal sepsis, specifically targets the human receptor CEACAM1. This interaction triggers events that would favor the development of puerperal sepsis, including adhesion to cervical cells, suppression of epithelial wound repair and subversion of innate immune responses. High-resolution structural analysis showed that an R28 domain with IgI3-like fold binds to the N-terminal domain of CEACAM1. Together, these findings demonstrate that a single adhesin-receptor interaction can drive the pathogenesis of bacterial sepsis and provide molecular insights into the pathogenesis of one of the most important infectious diseases in medical history.

Multilevel Pharmacological Effects of Antipsychotics in Potential Glioblastoma Treatment.

Glioblastoma Multiforme (GBM) is a debilitating type of brain cancer with a high mortality rate. Despite current treatment options such as surgery, radiotherapy, and the use of temozolomide and bevacizumab, it is considered incurable. Various methods, such as drug repositioning, have been used to increase the number of available treatments. Drug repositioning is the use of FDA-approved drugs to treat other diseases. This is possible because the drugs used for this purpose have polypharmacological effects. This means that these medications can bind to multiple targets, resulting in multiple mechanisms of action. Antipsychotics are one type of drug used to treat GBM. Antipsychotics are a broad class of drugs that can be further subdivided into typical and atypical classes. Typical antipsychotics include chlorpromazine, trifluoperazine, and pimozide. This class of antipsychotics was developed early on and primarily works on dopamine D2 receptors, though it can also work on others. Olanzapine and Quetiapine are examples of atypical antipsychotics, a category that was created later. These medications have a high affinity for serotonin receptors such as 5- HT2, but they can also act on dopamine and H1 receptors. Antipsychotic medications, in the case of GBM, also have other effects that can affect multiple pathways due to their polypharmacological effects. These include NF-B suppression, cyclin deregulation, and -catenin phosphorylation, among others. This review will delve deeper into the polypharmacological, the multiple effects of antipsychotics in the treatment of GBM, and an outlook for the field's future progression.

MXene-Assisted Ablation of Cells with a Pulsed Near-Infrared Laser.

Innovative therapies are urgently needed to combat cancer. Thermal ablation of tumor cells is a promising minimally invasive treatment option. Infrared light can penetrate human tissues and reach superficial malignancies. MXenes are a class of 2D materials that consist of carbides/nitrides of transition metals. The transverse surface plasmons of MXenes allow for efficient light absorption and light-to-heat conversion, making MXenes promising agents for photothermal therapy (PTT). To date, near-infrared (NIR) light lasers have been used in PTT studies explicitly in a continuous mode. We hypothesized that pulsed NIR lasers have certain advantages for the development of tailored PTT treatment targeting tumor cells. The pulsed lasers offer a wide range of controllable parameters, such as power density, duration of pulses, pulse frequency, and so on. Consequently, they can lower the total energy applied and enable the ablation of tumor cells while sparing adjacent healthy tissues. We show for the first time that a pulsed 1064 nm laser could be employed for selective ablation of cells loaded with Ti3C2Tx MXene. We demonstrate both low toxicity and good biocompatibility of this MXene in vitro, as well as a favorable safety profile based on the experiments in vivo. Furthermore, we analyze the interaction of MXene with cells in several cell lines and discuss possible artifacts of commonly used cellular metabolic assays in experiments with MXenes. Overall, these studies provide a basis for the development of efficient and safe protocols for minimally invasive therapies for certain tumors.

The Expression of Prolactin Receptors in Benign Breast Tumors Is Not Associated with Serum Prolactin Level.

The role of prolactin (PRL) and its receptors in the initiation and development of benign breast tumors (BBT) has not been sufficiently studied. An imbalance in the system of hormone homeostasis is crucial in the development of BBT. In particular, an association between elevated prolactin levels and the development of BBT has been reported. Our study showed no significant differences between PRL receptor (PRL-R) expression in BBT tissue under normal and elevated serum PRL levels. There was also no significant correlation between age, PRL-R expression in BBT tissue, intact tissue, and PRL level in the serum. There was a strong significant correlation (p < 0.01; r = 0.92) between PRL-R expression in BBT samples and intact breast tissue, which did not depend on the serum PRL level. There was also no significant difference in the expression of the proliferative marker Ki-67 in BBT tissues from women with normal and elevated levels of serum PRL (p > 0.05). No signs of PRL and its receptors were detected in the BBT cystic fluid women with elevated serum PRL levels. In summary, our prospective study showed that the expression of PRL-R in the tissue of BBT and physiological breast tissue does not depend on the level of serum PRL.

Low-frequency ultrasound increase effectiveness of silver nanoparticles in a purulent wound model.

Bacterial biofilm formation and antibiotic resistance are the main factors of surgical wound complications. Traditional treatments in some cases cannot provide complete bacterial eradication and new therapeutic approaches should be developed to overcome antibiotic resistance. Silver nanoparticles (AgNPs) can be the first choice for bacteria treatment but their clinical application is limited due to toxic effects. Combination of AgNPs with the low-frequency ultrasound (US) treatment expected to decrease toxicity and leads to the facilitation of wound healing. In current research we investigated the antibacterial activity of AgNPs per se and in combination with low-frequency US, assessed the cytotoxicity of AgNPs on human dermal fibroblasts and finally, wound healing was evaluated in purulent wound model (96 white laboratory rats) applying AgNPs and US as a treatment strategy. Our results demonstrate no toxic effect of AgNPs in minimum inhibitory concentrations and show increasing their antibacterial effectiveness after US application. The combination of low-frequency US and AgNPs provides reduction of the inflammatory reaction, microorganism elimination and leads to facilitation of new tissue formation with complete epithelization. All effects were significant over the Chlorhexidine treatment, monotherapy with AgNPs or US. Advanced effectiveness of complex therapy opens new perspectives for clinical application of AgNPs solution accompanied by US.