s100 protein
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Biomolecules ◽  
2022 ◽  
Vol 12 (1) ◽  
pp. 120
Author(s):  
Alexey S. Kazakov ◽  
Evgenia I. Deryusheva ◽  
Andrey S. Sokolov ◽  
Maria E. Permyakova ◽  
Ekaterina A. Litus ◽  
...  

Erythropoietin (EPO) is a clinically significant four-helical cytokine, exhibiting erythropoietic, cytoprotective, immunomodulatory, and cancer-promoting activities. Despite vast knowledge on its signaling pathways and physiological effects, extracellular factors regulating EPO activity remain underexplored. Here we show by surface plasmon resonance spectroscopy, that among eighteen members of Ca2+-binding proteins of the S100 protein family studied, only S100A2, S100A6 and S100P proteins specifically recognize EPO with equilibrium dissociation constants ranging from 81 nM to 0.5 µM. The interactions occur exclusively under calcium excess. Bioinformatics analysis showed that the EPO-S100 interactions could be relevant to progression of neoplastic diseases, including cancer, and other diseases. The detailed knowledge of distinct physiological effects of the EPO-S100 interactions could favor development of more efficient clinical implications of EPO. Summing up our data with previous findings, we conclude that S100 proteins are potentially able to directly affect functional activities of specific members of all families of four-helical cytokines, and cytokines of other structural superfamilies.


2022 ◽  
Author(s):  
Ban Hussein Alwash ◽  
Rawan Asaad Jaber Al-Rubaye ◽  
Mustafa Mohammad Alaaraj ◽  
Anwar Yahya Ebrahim

The dynamic alterations in the cytoskeletal components actin and intermediate, etc. filaments are required for cell invasion and migration. The actin cytoskeleton is a highly dynamic structure that is governed by a delicate balance of actin filament formation and disassembly. To controlling the activities of key components of the epithelial mesenchymal transition (EMT) could be a viable solution to metastasis. Bioinformatics technologies also allow researchers to investigate the consequences of synthetic mutations or naturally occurring variations of these cytoskeletal proteins. S100A4 is S100 protein family member that interact with a variety of biological target. In study has shown that S100A4 interacts with the tumor suppressor protein p53, indicating that S100A4 may have additional roles in tumor development. The S100A4 and p53 interaction increases after inhibition of MDM2-dependent p53 degradation using Nutlin-3A. The main goal of this research was control of cytoskeletal dynamics in cancer through a combination of, actin and S100A4 protein. The investigate the molecular mechanism behind S100A4 function in (EMT) and indicating that S100A4 is promoting p53 degradation. Understanding the signaling pathways involved would provide a better understanding of the changes that occur during metastasis, which will eventually lead to the identification of proteins that can be targeted for treatment, resulting in lower mortality.


2021 ◽  
pp. 29-38
Author(s):  
V. A. Osipov ◽  
A. N. Pastukhov ◽  
O. I. Kurbatov ◽  
Yu. P. Potekhina

Introduction. In recent decades, medical science has accumulated convincing evidence of the fact that the normal activity of a human brain depends on the functional integration of its vascular system, a circulation system of cerebrospinal fluid and biomechanical features of a skull, forming a single structural and functional system.The aim of the study is to research the histological structure of functionally significant cranial synchondroses in the middle and elderly age group, to find possible points of osteopathic influence application in their structure. Materials and methods. The study was performed on cadaver material of 27 persons (7 men — 26 %, 20 women — 74 %) who died at the age from 49 to 66 years (57,5±5,3 years) from various somatic pathologies, but had no history of craniocerebral injuries with fractures of osseous structures. Small bone fragments with sutures of interest/synchondroses (spheno-occipital synchondrosis, petro-jugular synchondrosis, sphenopetrosal synchondrosis) were subjected to standard histological processing followed by microscopy.Results. Evaluating histological specimens of spheno-occipital synchondrosis, we observed the similar pattern: highly mineralized tissues at the edges of the bodies of the sphenoid and occipital bones were connected without elements of cartilagi-nous or connective tissue. In all cases, no fibrous or nerve tissue elements were found during the in situ immunohistochemical reactions. Reactions with the CD34 antibody mark multiple vessels of the Volkmann's or Haversian canals. Evaluating histological specimens of petro-jugular and sphenopetrosal synchondroses, we found the presence of cartilage tissue in the suture in the form of small islands of various sizes (from 20 to 120 microns) with signs of degeneration and a small number of remained chondrocytes. When evaluating specimens with immunohistochemical reactions with antibodies against the S100 protein, no elements of the nervous tissue were detected.Conclusion. Spheno-occipital synchondrosis has a temporary nature. With age, its cartilaginous tissue is replaced by osseous one. According to the histological structure, sphenobasilar synchondrosis demonstrates the complete absence of a cartilaginous component in the middle and elderly age groups. Petro-jugular and sphenopetrosal synchondroses retain the cartilaginous component in their suture throughout lifetime. During histological examination of the petro-jugular and sphenopetrosal synchondroses, the cartilaginous component is represented by variety of small islands. In all synchondroses, there is an absence of vascular and nervous components. At the same time, we revealed the presence of a prominent vascular bed in the bone tissue. The fact requires emphasizing the importance of liquid potency and elastic component in cartilaginous and osseous tissues as an application point for osteopathic techniques.


2021 ◽  
Author(s):  
He Tong ◽  
Li Wang ◽  
Kefan Zhang ◽  
Jing Shi ◽  
yongshuai Wu ◽  
...  

Abstract BackgroundThe phagocytic S100 protein, which mediates inflammatory responses and recruits inflammatory cells to sites of tissue damage, has long been known to be expressed in cells of myeloid origin. S100A6 belongs to the A group of the S100 protein family of Ca2+-binding proteins. Currently, the mechanism by which S100A6 mediates the inflammatory response and recruits inflammatory cells to the tissue injury site is unknown.MethodsA mouse model of carbon tetrachloride (CCl4)-induced acute liver injury (ALI) was established, and the transcriptomes of postinjury 2d and 5d liver tissues were sequenced. Enzyme-linked immunosorbent assay was used to determine the expression of inflammatory factors (TNF-α, IL-1β, IL-6, and IL-8) in the supernatant of the liver. Immunohistochemical analysis confirmed the expression of S100A6 in the liver cells. In vitro experiments proved the pro-inflammatory function of S100A6, and western blotting (WB) showed that the pathways were activated. The transwell experiment showed the infiltration of mononuclear/macrophages.ResultsWe found that S100A6 is highly expressed in liver cells during the most severe period of ALI, suggesting that it acts as an endogenous danger signal and has a pro-inflammatory function. In vitro, the mouse S100A6 recombinant protein was used to stimulate liver Kupffer cells to promote the secretion of TNF-α, IL-1β, IL-6, and IL-8. Further mechanistic experiments revealed that S100A6 acts as an endogenous danger signal to activate p-P38 and p-JNK downstream of the TLR4 and P65 pathways. Similarly, transcriptome data showed that S100A6 can activate the inflammatory response in Kuffer cells. WB revealed that S100A6 had no significant effect on cell apoptosis. To continue to explore the mechanism of monocyte/macrophage infiltration, we found that TNF-α stimulates liver cells as the main source of CCL2. TNF-α can initiate the p-P38 and p-JNK pathways of liver cells to produce CCL2, thereby recruiting the infiltration of mononuclear/macrophages. ConclusionsTaken together, S100A6 is an endogenous danger signal that mediates inflammatory responses and recruits inflammatory cells to sites of tissue damage.


Biology ◽  
2021 ◽  
Vol 10 (12) ◽  
pp. 1286
Author(s):  
Ourania Parra ◽  
Konstantinos Linos

“Cutaneous melanocytic tumor with CRTC1::TRIM11 fusion” (CMTCT) is a recently described entity belonging to the family of superficial tumors displaying melanocytic differentiation. Thirteen cases have been reported so far, on the head and neck, extremities, and trunk of adults of all ages (12 cases) and one in an 11-year-old child. Histopathologically, it is a nodular or multilobulated tumor composed of spindle and epithelioid cells arranged in nests, fascicles, or bundles that are surrounded by thin collagenous septa. By immunohistochemistry, the tumor shows variable immunoreactivity for S100-protein, SOX10, and MITF, as well as specific melanocytic markers such as MelanA and HMB-45. The neoplasm’s biologic behavior remains uncertain since the reported cases are limited and the follow-up is short (median 12 months). However, local recurrence and synchronous distant metastasis after 13 years of initial resection has been described in one case. Herein, we present a comprehensive literature review of CMTCT hoping to raise awareness among the dermatopathologists of this potentially novel entity.


2021 ◽  
Vol 48 (1) ◽  
Author(s):  
Rania Abd El-Hamid El-Kady ◽  
Ayah Fathy ◽  
Talaat Othman ◽  
Eman Hafez

Abstract Background The advent of novel biologic agents for the treatment of rheumatoid arthritis (RA) has proven to be highly productive. Nonetheless, high cost, side effects, and unresponsiveness to these agents dictates the assignment of biomarkers that can foretell treatment response. Currently, calprotectin (a member of the S100 protein family) is amongst the enormously studied candidates in this perspective. Yet, conflicting results have been published. The main purpose of this study was to explore the role of serum concentration of calprotectin to predict the response to biological therapy in RA patients, so as to customize RA treatment. Results Baseline serum calprotectin levels were significantly higher in RA patients compared to the control subjects (P value < 0.001). After receiving biologic therapy, a remarkable reduction (P < 0.001) in serum calprotectin was noted in RA cohort. Moreover, no correlation was found between the 28 joint count disease activity score (DAS28) and serum calprotectin levels neither before or after biologics. Intriguingly, no statistically significant association was detected between circulating calprotectin level and response to biological therapy. Conclusion Serum calprotectin concentrations could not be used as a biomarker to forecast clinical response to biological therapy in RA patients. However, further studies involving larger cohort of RA patients should be carried out to deliver more insight in this regard.


Medicina ◽  
2021 ◽  
Vol 57 (12) ◽  
pp. 1313
Author(s):  
Alessia Todeschini ◽  
Ilaria Loconte ◽  
Antonella Contaldo ◽  
Enzo Ierardi ◽  
Alfredo Di Leo ◽  
...  

A 80-year-old woman underwent vulvar melanoma resection and segmental lung resection for pulmonary metastasis. Immunotherapy with Nivolumab was performed. One year later, the patient was admitted for gastrointestinal (GI) recurrent bleeding and severe anemia. Esophagoastroduodenoscopy and colonoscopy did not show any abnormality, while videocapsule endoscopy (VCE) revealed an irregular and exophytic whitish area with a “coal-black” central depression. Small bowel resection was performed and histological examination revealed S100 protein strongly positive melanoma metastasis. The patient died six months later from disease progression. A “coal-black” appearance of intestinal metastatic melanoma has been described only twice before this report. In one case the patient had been treated by immunotherapy with interferon A and dendritic cell-based vaccination. In our patient, it is presumable that the picture we observed was a consequence of Nivolumab treatment inducing the disappearance of melanocytes in the area surrounding the metastasis with the onset of the central coal-black lesion encircled by whitish tissue. This picture should be emblematic of intestinal metastatic melanoma in subjects treated with immunotherapy showing occult/obscure bleeding.


2021 ◽  
Author(s):  
Ying Wan ◽  
Ying Zhang ◽  
Zhongguo Pang ◽  
Changli Lu ◽  
Lili Jiang

Abstract BackgroundPrimary tracheobronchial granular cell tumors (GCTs) are rare. The characteristics of these tumors are unclear, and they are easily misdiagnosed. Thus, the present study aimed to investigate the clinicopathological features and immunophenotype profile of these tumors of the tracheobronchial tree.MethodsFour patients were treated for GCTs of the tracheobronchial tree at our institution during 2009–2020. The clinicopathologic and immunohistochemical (IHC) findings were performed in all cases. In addition, seven typical GCTs involving the subcutaneous tissues (4/7) and esophagus (3/7) were also selected as control groups to evaluate the differences in IHC characteristics in different locations. Fisher’s exact test was adopted in analysis of categorical data.ResultsThere were four patients, two females and two males, aged 15, 22, 45 and 52. Three tracheobronchial tumors were solitary with a range from 2.0 to 3.1 cm (mean, 2.6 cm) in its large axis, while one sample was multiple. Chest computed tomography (CT) often suggested lung infectious lesions. On histopathology, three samples were typical GCTs, and the other sample was atypical with a fusiform or spindled morphology. All tumor cells stained positive for S100 protein, CD68, and Nestin and negative for Inhibin-α and thyroid transcription factor-1(TTF-1). The Ki-67 index was less than 5%. Tracheobronchial GCTs exhibited occasional focal and weakly positive transcription factor E3 (TFE3) staining and had a lower ratio than those in other sites, while calretinin showed predominant subcutaneous expression. Two patients treated with tumor resection and the others only performed an endoscopic biopsy. Follow-up period ranged from 24 to 68 months with a mean of 42 months.ConclusionsPrimary tracheobronchial GCTs are rare and are often mimics pneumonia, which have a good prognosis even without surgical resections. Tracheobronchial GCTs had an unusual immunophenotype of TFE3 expression compared with other sites. This result may reflect a site-specific phenomenon distinguishing GCTs of the tracheobronchial tree.


2021 ◽  
Vol 2021 ◽  
pp. 1-3
Author(s):  
Benjamin van Haeringen ◽  
Leo Francis ◽  
Emily Olive ◽  
Daniel James

Signet ring cell morphology may result from a variety of causes and ranges from a benign reactive phenomenon to being indicative of highly aggressive malignancy. Benign epithelial signet ring cell change is well described in a variety of tissues, but nonepithelial signet ring cell change is a rare morphologic adaptation of adipose tissue principally described in the setting of cachexia. The location of these atrophic adipocytes outside the plane of normal epithelial layers may raise concern for invasive or metastatic malignancy, and consideration of a benign reactive process is critical to avoid catastrophic overdiagnosis and overtreatment. Further, this change is itself associated with significant mortality related to the underlying cachexia and may be important to highlight to treating clinicians. Compared to malignant signet ring cell carcinoma, benign signet ring cell change is more likely to retain normal lobulated architecture without mass formation, lack significant atypia, have myxoid stroma with a prominent capillary network, and show positive staining S100 protein with negative staining for cytokeratins and mucin. To our knowledge, we present the first described case of nonepithelial signet ring cell change involving the gallbladder, detected as an incidental finding following routine cholecystectomy in an elderly cachectic man.


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