Tumor neuroectodérmico maligno del tracto gastrointestinal: a propósito de un caso / Malignant neuroectodermal tumor of the gastrointestinal tract: case report

El tumor neuroectodérmico maligno del tracto gastrointestinal es una neoplasia rara con pocos casos reportados en la literatura, especialmente en América Latina. Descrito por primera vez en 2003, se trata de una entidad sin tratamiento estandarizado y de pobre pronóstico. Se presenta el caso de una paciente de 22 años de edad que acude a la consulta por dolor abdominal, anemia y masa abdominal palpable. Luego de estudios pertinentes se decide la conducta resectiva y el posterior tratamiento oncológico. (AU)

Malignant gastrointestinal neuroectodermal tumor (GNET), formerly known as clear cell sarcoma of the gastrointestinal tract, is an extremely rare tumor of mesenchymal origin, which presents great microscopic and molecular similarity to clear cell sarcoma found in other parts of the body, such as tendons and aponeurosis. It is characterized by its rapid evolution, high recurrence rate and frequent diagnosis as metastatic disease.1,2 (AU)

The mechanism of S100A7 inducing the migration and invasion in cervical cancer cells / 中华肿瘤杂志

Objective: To investigate the mechanism of S100A7 inducing the migration and invasion in cervical cancers. Methods: Tissue samples of 5 cases of cervical squamous cell carcinoma and 3 cases of adenocarcinoma were collected from May 2007 to December 2007 in the Department of Gynecology of the Affiliated Hospital of Qingdao University. Immunohistochemistry was performed to evaluate the expression of S100A7 in cervical carcinoma tissues. S100A7-overexpressing HeLa and C33A cells were established with lentiviral systems as the experimental group. Immunofluorescence assay was performed to observe the cell morphology. Transwell assay was taken to detect the effect of S100A7-overexpression on the migration and invasion of cervical cancer cells. Reverse transcription-quantitative real-time polymerase chain reaction (RT-qPCR) was used to examine the mRNA expressions of E-cadherin, N-cadherin, vimentin and fibronectin. The expression of extracellular S100A7 in conditioned medium of cervical cancer cell was detected by western blot. Conditioned medium was added into Transwell lower compartment to detect cell motility. Exosomes were isolated and extracted from the culture supernatant of cervical cancer cell, the expressions of S100A7, CD81 and TSG101 were detected by western blot. Transwell assay was taken to detect the effect of exosomes on the migration and invasion of cervical cancer cells. Results: S100A7 expression was positively expressed in cervical squamous carcinoma and negative expression in adenocarcinoma. Stable S100A7-overexpressing HeLa and C33A cells were successfully constructed. C33A cells in the experimental group were spindle shaped while those in the control group tended to be polygonal epithelioid cells. The number of S100A7-overexpressed HeLa cells passing through the Transwell membrane assay was increased significantly in migration and invasion assay (152.00±39.22 vs 105.13±15.75, P<0.05; 115.38±34.57 vs 79.50±13.68, P<0.05). RT-qPCR indicated that the mRNA expressions of E-cadherin in S100A7-overexpressed HeLa and C33A cells decreased (P<0.05) while the mRNA expressions of N-cadherin and fibronectin in HeLa cells and fibronectin in C33A cells increased (P<0.05). Western blot showed that extracellular S100A7 was detected in culture supernatant of cervical cancer cells. HeLa cells of the experimental group passing through transwell membrane in migration and invasion assays were increased significantly (192.60±24.41 vs 98.80±47.24, P<0.05; 105.40±27.38 vs 84.50±13.51, P<0.05) when the conditional medium was added into the lower compartment of Transwell. Exosomes from C33A cell culture supernatant were extracted successfully, and S100A7 expression was positive. The number of transmembrane C33A cells incubated with exosomes extracted from cells of the experimental group was increased significantly (251.00±49.82 vs 143.00±30.85, P<0.05; 524.60±52.74 vs 389.00±63.23, P<0.05). Conclusion: S100A7 may promote the migration and invasion of cervical cancer cells by epithelial-mesenchymal transition and exosome secretion.

Predictive value of calprotectin for acute kidney injury in patients with sepsis / 中华急诊医学杂志

Objective:To explore the predictive value and prognosis effect of calprotectin on acute kidney injury (AKI) in patients with sepsis.Methods:A prospective observational study was conducted. From December 2018 to November 2020, patients with sepsis admitted to the Emergency Department of China Rehabilitation Research Center were enrolled. General clinical data of patients were collected continuously, and the acute physiology and chronic health evaluationⅡ (APACHEⅡ) score, sequential organ failure assessment (SOFA) score and calprotectin were evaluated in 24 h after admission. The patients were divided into the AKI group and non-AKI group according to the occurrence of AKI within 7 days after admission. Calprotectin level and other clinical data were compared between the two groups. Logistic regression was used to analyze the risk factors for AKI in patients with sepsis, and receiver operating characteristic (ROC) curve was plotted to evaluate the predictive value of calprotectin for AKI in patients with sepsis. The patients with AKI were further divided into the survival group and death group according to the 28-day outcome, and the calprotectin levels between the two groups were compared.Results:A total of 207 patients with sepsis were enrolled, and the incidence of AKI was 68.12% (141/207). The level of calprotectin in patients with AKI was higher than that in patients without AKI [4.65 (3.25, 5.61) μg/mL vs. 3.42 (2.29, 4.09) μg/mL, P < 0.001]. Multivariable Logistic regression analysis showed that APACHEⅡ score ( OR=1.090, 95% CI: 1.043-1.139), C-reactive protein ( OR=1.004, 95% CI: 1.001-1.008) and calprotectin ( OR=1.590, 95% CI: 1.269-1.991) were independent risk factors for AKI in patients with sepsis. The area under ROC curve (AUC) of calprotectin for predicting AKI was 0.716 (95% CI: 0.643-0.788). The cutoff value of prediction was 4.63 μg/mL with the Yoden index of 0.405, which yielded a sensitivity of 0.511 and a specificity of 0.894. When calprotectin was combined with APACHE II score and SOFA score respectively, the predictive ability was significantly improved with the AUC of 0.768 (95% CI: 0.701-0.834) and 0.769 (95% CI: 0.701-0.837), respectively. We further divided patients with AKI into the survival group and non-survival group according to the 28-day outcome and there was no significant difference in calprotectin between the two groups [4.80 (3.40, 5.76) μg/mL vs. 4.19 (2.89, 5.29) μg/mL, P < 0.05]. Conclusions:The level of calprotectin in the AKI group is higher than that in the non-AKI group. Calprotectin can be regarded as an effective predictor of AKI in patients with sepsis, and the combination with APACHEⅡ score or SOFA score will improve its predictive efficacy. However, there is no significant difference in the concentration of calprotectin for patients with sepsis associated AKI with different prognosis.

Progress of major biomarkers for neonatal brain injury in clinical application / 国际儿科学杂志

With the continuous progress of monitoring and treatment skills, the mortality of neonates has gradually decreased, and the long-term neurodevelopmental outcome has become the primary concern of society and families.During the perinatal period, the developing brain is vulnerable to hypoxia, hemorrhage, infection and inflammation, which may cause varying degrees of brain cell damage.Studies have found that proteins released by damaged brain cells can be detected in the body fluid of neonates, which are related to the occurrence and prognosis of neonatal brain injury.This article mainly reviews the recently reported brain injury biomarkers such as S100B, neuron specific enolase(NSE)and glial fibrillary acidic protein(GFAP)in different biological samples and its clinical predictive value for the occurrence of brain injury and neurodevelopmental prognosis.

S100A10 promotes proliferation and invasion of lung adenocarcinoma cells by activating the Akt-mTOR signaling pathway / 南方医科大学学报

OBJECTIVE@#To investigate the effects of expression levels of S100 calcium-binding protein A10 (S100A10) in lung adenocarcinoma (LUAD) on patient prognosis and the regulatory role of S100A10 in lung cancer cell proliferation and metastasis.@*METHODS@#Immunohistochemistry was used to detect the expression levels of S100A10 in LUAD and adjacent tissues, and the relationship between S100A10 expression and clinicopathological parameters and prognosis of the patients was statistically analyzed. The lung adenocarcinoma expression dataset in TCGA database was analyzed using gene enrichment analysis (GSEA) to predict the possible regulatory pathways of S100A10 in the development of lung adenocarcinoma. Lactate production and glucose consumption of lung cancer cells with S100A10 knockdown or overexpression were analyzed to assess the level of glycolysis. Western blotting, CCK-8 assay, EdU-594 assay, and Transwell assays were performed to determine the expression level of S100A10 protein, proliferation and invasion ability of lung cancer cells. A549 cells with S100A10 knockdown and H1299 cells with S100A10 overexpression were injected subcutaneously in nude mice, and tumor growth was observed.@*RESULTS@#The expression level of S100A10 was significantly upregulated in LUAD tissues as compared with the adjacent tissues, and an elevated S100A10 expression level was associated with lymph node metastasis, advanced tumor stage and distant organ metastasis (P < 0.05), but not with tumor differentiation or the patients' age or gender (P > 0.05). Survival analysis showed that elevated S100A10 expressions in the tumor tissue was associated with a poor outcome of the patients (P < 0.001). In the lung cancer cells, S100A10 overexpression significantly promoted cell proliferation and invasion in vitro (P < 0.001). GSEA showed that the gene sets of glucose metabolism, glycolysis and mTOR signaling pathway were significantly enriched in high expressions of S100A10. In the tumor-bearing nude mice, S100A10 overexpression significantly promoted tumor growth, while S100A10 knockdown obviously suppressed tumor cell proliferation (P < 0.001).@*CONCLUSION@#S100A10 overexpression promotes glycolysis by activating the Akt-mTOR signaling pathway to promote proliferation and invasion of lung adenocarcinoma cells.

Effect of transcranial direct current stimulation on neurological injury markers and prognosis in patients with acute and severe carbon monoxide poisoning / 中华劳动卫生职业病杂志

Objective: To observe the effects of transcranial direct current stimulation (tDCS) on nerve injury markers and prognosis in patients with acute severe carbon monoxide poisoning (ASCOP) . Methods: In May 2021, 103 ASCOP patients were treated in the emergency department of Harrison International Peace Hospital of Hebei Medical University from November 2020 to January 2021. The patients were divided into two groups according to whether they received tDCS treatment. The control group (50 cases) were given oxygen therapy (hyperbaric oxygen and oxygen inhalation) , reducing cranial pressure, improving brain circulation and cell metabolism, removing oxygen free radicals and symptomatic support, and the observation group (53 cases) was treated with 2 weeks of tDCS intensive treatment on the basis of conventional treatment. All patients underwent at least 24 h bispectral index (BIS) monitoring, BIS value was recorded at the hour and the 24 h mean value was calculated. Neuron-specific enolase (NSE) and serum S100B calcium-binding protein (S100B) were detected after admission, 3 d, 7 d and discharge. Follow-up for 60 days, the incidence and time of onset of delayed encephalopathy (DEACMP) with acute carbon monoxide poisoning in the two groups were recorded. Results: The NSE and S100B proteins of ASCOP patients were significantly increased at admission, but there was no significant difference between the two groups (P=0.711, 0.326) . The NSE and S100B proteins were further increased at 3 and 7 days after admission. The increase in the observation group was slower than that in the control group, and the difference was statistically significant (P(3 d)=0.045, 0.032, P(7 d)=0.021, 0.000) ; After 14 days, it gradually decreased, but the observation group decreased rapidly compared with the control group, with a statistically significant difference (P=0.009, 0.025) . The 60 day follow-up results showed that the incidence of DEACMP in the observation group was 18.87% (10/53) , compared with 38.00% (19/50) in the control group (P=0.048) ; The time of DEACMP in the observation group[ (16.79±5.28) d] was later than that in the control group[ (22.30±5.42) d], and the difference was statistically significant (P=0.013) . Conclusion: The early administration of tDCS in ASCOP patients can prevent the production of NSE and S100B proteins, which are markers of nerve damage. and can improve the incidence and time of DEACMP.

Superexpressão do receptor de Inositol 1,4, 5-trifosfato isoforma 3 (ITPR3) em colangiocarcinoma e sua correlação com a proteína dependente de cálcio S100A4 / Inositol 1,4, 5-triphosphate receptor isoform 3 (ITPR3) overexpression in cholangiocarcinoma and its correlation with calcium-dependent protein S100A4

O colangiocarcinoma (CCA) é a segunda neoplasia mais maligna do fígado que surge na árvore biliar. O CCA está associado com mau prognóstico e os principais fatores envolvidos em sua patogênese não são bem compreendidos. Os receptores tirosina quinases (RTKs), como o receptor do fator de crescimento epidérmico (EGFR), podem mediar as vias de sinalização de cálcio intracelular (Ca 2+ ), via inositol 1,4,5-trifosfato (InsP3). Eles ativam os receptores 1,4,5-trifosfato (ITPRs) e regulam o crescimento tumoral. ITPR isoforma 3 é o principal canal de liberação intracelular de Ca 2+ em colangiócitos. Os efeitos do Ca 2+ intracelular, por sua vez são mediados por proteínas de ligação de cálcio, como calmodulina e proteína A4 de ligação de cálcio S100 (S100A4). No entanto, o significado clínico patológico e biológico de EGFR, ITPR3 e S100A4 no CCA permanece obscuro. Assim, o presente trabalho investiga a imuno exprepressão dessas três proteínas em 59 pacientes diagnosticados com CCA, submetidos a tratamento cirúrgico curativo e correlaciona os dados com características clínico-patológicas e sobrevida. A alta expressão de ITPR3 foi correlacionada com os níveis de CA 19-9, estágio TNM e metástases em linfonodos (N). Além disso, a expressão de ITPR3 foi aumentada em CCA distal em comparação com ductos biliares de controle e CCAs intra-hepáticos e peri-hilares. Os escores clínicos ITPR3 e S100A4 foram significativamente correlacionados. Em resumo, a super expressão de ITPR3 pode contribuir para a progressão da CCA e pode representar um potencial alvo terapêutico. Palavras-chave: ITPRs; ITPR3; S100A4; Colangiocarcinoma; Fígado; Câncer

Cholangiocarcinoma (CCA) is the second most malignant neoplasm in the liver that arises from the biliary tree. CCA is associated with a poor prognosis, and the key players involved in its pathogenesis are still not well understood. Receptor tyrosine kinases (RTKs), such as epidermal growth factor receptor (EGFR), can mediate intracellular calcium (Ca2+) signaling pathways via inositol 1,4,5trisphosphate (InsP3), activating inositol 1,4,5-trisphosphate receptors (ITPRs) and regulating tumor growth. ITPR isoform 3 (ITPR3) is the main intracellular Ca2+ release channel in cholangiocytes. The effects of intracellular Ca2+ are mediated by calciumbinding proteins such as Calmodulin and S100 calcium-binding protein A4 (S100A4). However, the clinicopathological and biological significance of EGFR, ITPR3 and S100A4 in CCA remains unclear. Thus, the present work investigates the immunoexpression of these three proteins in 59 CCAs from patients who underwent curative surgical treatment and correlates the data with clinicopathological features and survival. High ITPR3 expression was correlated with CA 19-9 levels, TNM stage and lymph node metastasis (N). Furthermore, ITPR3 expression was increased in distal CCA compared to control bile ducts and intrahepatic and perihilar CCAs. In summary, ITPR3 overexpression could contribute to CCA progression and it may represent a potential therapeutic target.

Performance of fecal S100A12 as a novel non-invasive diagnostic biomarker for pediatric inflammatory bowel disease: a systematic review and meta-analysis

Abstract Objective: The incidence and prevalence of inflammatory bowel disease (IBD) in pediatric patients are increasing. Currently, the diagnostic method for IBD is inconvenient, expensive, and difficult. S100A12, a type of calcium-binding protein, detected in the feces of patients with IBD has recently been suggested as a promising diagnostic tool. Hence, the authors aimed to evaluate the accuracy of fecal S100A12 in diagnosing IBD in pediatric patients by performing a meta-analysis. Methods: The authors performed a systematic literature search in five electronic databases for eligible studies up to July 15, 2021. Pooled diagnostic accuracies of fecal S100A12 were analyzed as the primary outcomes. Secondary outcomes were standardized mean difference (SMD) of fecal S100A12 levels between IBD and non-IBD groups and a comparison of diagnostic accuracies between fecal S100A12 and fecal calprotectin. Results: Seven studies comprising 712 children and adolescents (474 non-IBD controls and 238 IBD cases) were included. Fecal S100A12 levels were higher in the IBD group than in the non-IBD group (SMD = 1.88; 95% confidence interval [CI] = 1.19-2.58; p < 0.0001). Fecal S100A12 could diagnose IBD in pediatric patients with a pooled sensitivity of 95% (95% CI = 88%-98%), specificity of 97% (95% CI = 95%-98%), and area under the receiver operating summary characteristics (AUSROC) curve of 0.99 (95% CI = 0.97-0.99). Fecal S100A12 specificity and AUSROC curve values were higher than those of fecal calprotectin (p < 0.05). Conclusion: Fecal S100A12 may serve as an accurate and non-invasive tool for diagnosing pediatric IBD. © 2023 Sociedade Brasileira de Pediatria. Published by Elsevier Editora Ltda. This is an open access article under the CC BY-NC-ND license (https://creativecommons.org/licenses/by-nc-nd/4.0/).

Evaluation of peripheral nerve fibers and mast cells in burning mouth syndrome

Abstract Emerging evidence has revealed a cross-talk in the etiopathogenesis of burning mouth syndrome (BMS) related to peripheral nerve fibers (NF) and neuropeptides secreted by mast cells. Here, we investigated the S-100+ density and PGP 9.5+ integrity of peripheral NF and the tryptase+ mast cell density in the oral mucosa of BMS patients and healthy individuals. A total of 23 oral mucosa specimens (12 BMS and 11 controls) were evaluated. The clinical diagnosis of BMS was based on a careful examination, excluding other local and systemic causes. Samples were taken from an incisional biopsy of the tongue mucosa of individuals with symptomatic BMS, while the margins of the non-neoplastic tongue biopsy served as controls of healthy individuals. Immunohistochemistry was performed to determine the density/mm2 of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells. Similar densities of S-100+, PGP 9.5+ peripheral NF, and tryptase+ mast cells were found in cases of BMS, with a median value of 3.70, 0.70, and 29.24/mm2, respectively, and in the control group, with a median value of 2.60, 0.80, and 26.01/mm2, respectively (p > 0.05). Moreover, the relationship between S100+ and PGP 9.5+ peripheral NF was the same in both groups (p = 0.70). This study demonstrated that there were no alterations in the density and integrity of peripheral NF in the tongue of symptomatic BMS patients. However, the sensitization of peripheral NF in this disease may not depend on mast cell density.

Changes of regional cerebral oxygen saturation, S100β protein and neuron specific enolase and their relationship with perioperative neurocognitive disorders in patients undergoing total aortic arch replacement and trunk stenting / 西安交通大学学报(医学版)

【Objective】 To investigate the predictive value of regional cerebral oxygen saturation (rScO2) monitoring during total aortic arch replacement and stent trunk surgery for perioperative neurocognitive disorders (PND) and changes in plasma S100β protein and neuron-specific enolase (NSE) concentrations and their relationship with PND. 【Methods】 Sixty-five Stanford type A aortic dissection patients who planned to undergo total aortic arch replacement and trunk stenting were selected. Their rScO2 values were monitored throughout the operation and recorded after induction (T1), the beginning of CPB (T2), during deep hypothermic circulatory arrest (T3), rewarming to 36℃(T4), CPB stop for 1 hour (T5), and post-operation (T6). After induction (Ta), rewarming to 36℃ (Tb),1 h (Tc), 6 h (Td) and 24 h (Te) after cessation of cardiopulmonary bypass, central venous blood was collected from patients, and the concentrations of S100β protein and NSE in plasma were detected by ELISA. The patients were divided into PND group and non-PND group by the evaluation of MMSE scale at time of before operation, on the day of extubation, and 7 days after operation. 【Results】 The incidence of PND was 44.6%. The rScO2 value at T2 was significantly lower than that at T1 (P<0.05). The rScO2 value of PND group at T3 and T6 was significantly lower than that at T1 and non-PND group (P<0.05). The mean value of rScO2 and the minimum value of rScO2 in PND group were significantly lower than those in non-PND group, while rScO2 %max in PND group was significantly higher than that in non-PND group (P<0.05). The intraoperative critical value of rScO2 %max was >9.89%, the area under curve (AUC) was 0.658 (95% CI: 0.525-0.791, P<0.05), and sensitivity and specificity were 48.3% and 75.0%, respectively. The concentrations of S100β protein and NSE protein in PND group were significantly higher than those in non-PND group at Tc and Td (P<0.01). Compared with Ta, the concentration of S100β protein in PND group was significantly increased at Tc and Td (P<0.001), and the concentration of NSE protein was significantly increased at Tb-Te (P<0.01). CPB time was an independent risk factor for PND. 【Conclusion】 The occurrence of PND after total arch replacement and stenting may be related to the decrease of rScO2 and the increase of S100β protein and NSE protein. Intraoperative rScO2 %max >9.89% can be a potential predictor of PND.

Progress of the relationship between S100A9 and breast cancer / 肿瘤研究与临床

S100A9 is a calcium-binding protein that plays an important role in the progression of malignant tumors. Related studies have confirmed that the abnormal expression of S100A9 is closely related to the proliferation, metastasis and prognosis of breast cancer, while whether S100A9 can be used as a marker for the diagnosis and treatment of breast cancer is still controversial. This article reviews the current research status of S100A9 and its application prospect in the development, progression, diagnosis and treatment of breast cancer.

Novel ALK-EML4 fusion with prominent mucous and hyaline stroma: Expanding the molecular genetic spectrum of S100 and CD34 positive spindle cell tumor

We report a case of a 49-year-old male patient suffering from an intraspinal tumor in the lumbar vertebra. The neoplasm was composed of mono-morphic spindle cells, arrayed in a patternless pattern in a background of prominent myxoid hyaline stroma with perivascular collagen rings in hyper-cellular regions. Instead, aggregated collagen fibers arranged into nodules and apparent calcium deposition were found in hypo-cellular regions. The tumor cells showed immunopositivity with S100 and CD34, whereas lacked SOX10 expression, which were reminiscent of a group of S100 and CD34 co-expression soft tissue spindle cell lesions having recurrent fusions including RAF1, BRAF, NTRK1/2/3, and RET genes. Interestingly, a novel anaplastic lymphoma kinase (ALK)- echinoderm microtubule-associated protein-like 4 (EML4) gene fusion was revealed. To our best knowledge, it was the first time to identify such gene fusion in the Orientals among this mentioned group, and it expands the molecular genetic spectrum of this specific group. The clinical relevance of this novel fusion requires further investigations.

Function of s100 protein in coronary atherosclerosis / Función de la proteína s100 en aterosclerosis coronaria

SUMMARY: Atherosclerosis is a complex disease whose pathogenesis includes endothelial activation, accumulation of lipids in the subendothelium, formation of foam cells, fat bands and formation of atherosclerotic plaque. These complex mechanisms involve different cell populations in the intimate sub-endothelium, and the S-100 protein family plays a role in a number of extracellular and intracellular processes during the development of atherosclerotic lesions. The aim of this study was to determine the phenotypic characteristics of smooth muscle cells and the consequent expression of S100 protein in atherosclerotic altered coronary arteries in advanced stages of atherosclerosis. 19 samples of right atherosclerotic coronary arteries in stages of fibro atheroma (type V lesion) and complicated lesions (type VI lesion) have been analyzed. According to the standard protocol, the following primary antibodies have been used in the immunohistochemical analysis: a-smooth muscle actin (α-SMA), vimentin and S-100 protein. All analyzed samples have been in advanced stages of atherosclerosis, fibro atheroma (stage V lesions) and complicated lesions (type VI lesions). Most of them have had the structure of a complicated lesion with atheroma or fibro atheroma as a basis, subsequently complicated by disruption (subtype VI a), hemorrhage (subtype VI b) or thrombosis (subtype VI c), as well as by the presence of several complications on the same sample. Marked hypocellularity is present in the subendothelium of plaques. Cell population at plaque margins is characterized by immunoreactivity to α-SMA, vimentin, and S100 protein. Some of these cells accumulate lipids and look like foam cells. In the cell population at the margins of the plaques, smooth muscle cells of the synthetic phenotype are present, some of which accumulate lipids and demonstrate S100 immunoreactivity. Summarizing numerous literature data and our results, we could assume that smooth muscle cells, due to their synthetic and proliferative activity in the earlier stages of pathogenesis, as well as the consequent expression of S100 protein, could accumulate lipids in the earlier stages of atherosclerosis which, in advanced stages analyzed in this study, result in immunoreactivity of foam cells of smooth muscle origin to S100 protein.

RESUMEN: La aterosclerosis es una enfermedad compleja cuya patogenia incluye activación endotelial, acumulación de lípidos en el subendotelio, formación de células espumosas, bandas grasas y formación de placa aterosclerótica. Estos complejos mecanismos involucran diferentes poblaciones celulares en el subendotelio íntimo, y la familia de proteínas S-100 juega un papel en varios procesos extracelulares e intracelulares durante el desarrollo de lesiones ateroscleróticas. El objetivo de este estudio fue determinar las características fenotípicas de las células de músculo liso y la consecuente expresión de la proteína S100 en arterias coronarias alteradas ateroscleróticas en estadios avanzados de aterosclerosis. Se analizaron 19 muestras de arterias coronarias ateroscleróticas derechas en estadios de fibroateroma (lesión tipo V) y lesiones complicadas (lesión tipo VI). Según el protocolo estándar, en el análisis inmunohistoquímico se utilizaron los siguientes anticuerpos primarios: α-actina de músculo liso (α-SMA), vimentina y proteína S-100. Todas las muestras analizadas han estado en estadios avanzados de aterosclerosis, fibroateroma (lesiones estadio V) y lesiones complicadas (lesiones tipo VI). La mayoría de ellos han tenido la estructura de una lesión complicada con ateroma o fibroateroma como base, complicada posteriormente por disrupción (subtipo VI a), hemorragia (subtipo VI b) o trombosis (subtipo VI c), así como por la presencia de varias complicaciones en la misma muestra. La hipocelularidad marcada estaba presente en el subendotelio de las placas. La población celular en los márgenes de la placa se caracterizaba por inmunorreactividad a α-SMA, vimentina y proteína S100. Algunas de estas células acumulan lípidos y parecen células espumosas. En la población celular en los márgenes de las placas, estaban presentes las células de músculo liso de fenotipo sintético, algunas de las cuales acumulaban lípidos y mostraban inmunorreactividad S100. Resumiendo numerosos datos de la literatura y nuestros resultados, podríamos suponer que las células del músculo liso, debido a su actividad sintética y proliferativa en las primeras etapas de la patogénesis, así como la consecuente expresión de la proteína S100, podrían acumular lípidos en las primeras etapas de la aterosclerosis que, en estadios avanzados analizados en este estudio, dan como resultado inmunorreactividad de células espumosas de origen muscular liso a la proteína S100.

Value of neuron specific enolase and S-100β protein in cerebrospinal fluid in the diagnosis and treatment of children with viral encephalitis and meningitis / 中国基层医药

Objective:To investigate the changes and clinical significance of neuron specific enolase (NSE) and S-100β protein levels in cerebrospinal fluid of children with viral encephalitis and meningitis.Methods:Sixty children with viral encephalitis and meningitis admitted to The Second Hospital of Jiaxing from February 2018 to December 2020 were included in the observation group. An additional 30 children without central nervous system diseases who concurrently received treatment in the same hospital were included in the control group. The value of NSE and S-100β protein levels in the diagnosis and treatment of viral encephalitis and meningitis in chiblren were analyzed.Results:NSE and S-100β protein levels in the observation group were (17.683 ± 1.321) μg/L and (1.755 ± 0.129) μg/L, respectively, which were significantly higher than (5.267 ± 0.907) μg/L and (0.827 ± 0.172) μg/L in the control group ( t = 46.25, 28.65, both P < 0.001). NSE and S-100β protein levels in children with mild viral encephalitis and meningitis were (15.219 ± 0.870) μg/L and (1.456 ± 0.113) μg/L, respectively, which were significantly lower than (19.893 ± 1.066) μg/L and (2.014 ± 0.085) μg/L in children with severe viral encephalitis and meningitis ( t = -18.69, -21.32, both P < 0.001). In children with viral encephalitis and meningitis, NSE and S-100β protein levels during the acute phase were (17.250 ± 1.188) μg/L and (1.683 ± 0.096) μg/L, respectively, which were significantly higher than (11.150 ± 0.971) μg/L and (1.147 ± 0.098) μg/L during the convalescence phase ( t = 30.79, 30.27, both P < 0.001). Conclusion:NSE and S-100β protein levels in cerebrospinal fluid of children with viral encephalitis and meningitis can help evaluate the severity of viral encephalitis and meningitis in children, providing important clinical application value for judging the development and prognosis of viral encephalitis and meningitis.

Changes and clinical significance of plasma S100A1 protein, nuclear factor-κB p65 and interleukin-6 levels in patients with acute ischemic cerebrovascular diseases / 中国基层医药

Objective:To investigate the changes and clinical significance of plasma S100A1 protein, nuclear factor-κB p65 (NF-κB p65) and interleukin-6 (IL-6) levels in patients with acute ischemic cerebrovascular diseases.Methods:A total of 141 patients with acute ischemic cerebral infarction (AICI; AICI group) and 20 patients with transient ischemic attack (TIA; TIA group) who received treatment in Northern Jiangsu People's Hospital from April to November 2020 were included in this study. According to the volume of cerebral infarct, the AICI group was subdivided into small-volume cerebral infarct (SCI group, n = 78), moderate-volume cerebral infarct (MCI group, n = 32) and large-volume cerebral infract (LCI group, n = 31) groups. An additional 31 healthy controls who concurrently received physical examination were included as controls (HC group). S100A1, NF-κB p65, and IL-6 levels were compared between AICI, TIA and HC groups and between SCI, MCI and LCI groups. S100A1, NF-κB p65, and IL-6 levels were correlated with the National Institutes of Health Stroke Scale score and the volume of cerebral infarct. The receiver operating characteristic curve (ROC) was drawn to analyze the diagnostic value of S100A1, NF-κB p65, and IL-6 levels for AICI. Results:S100A1, NF-κB p65, and IL-6 levels in the AICI group were (230.96 ± 39.37) ng/L, (3.99 ± 0.65) mg/L, (13.32 ± 1.57) ng/L, respectively, which were significantly higher than (185.85 ± 43.24) ng/L, (3.58 ± 0.74) mg/L, (11.61 ± 1.67) ng/L in the TIA group ( t = 4.95, 2.39, 4.14, all P < 0.05) and (181.47 ± 27.39) ng/L, (3.51 ± 0.99) mg/L, (11.42 ± 2.34) ng/L in the HC group ( t = 6.54, 3.32, 5.55, all P < 0.05). There were no significant differences in S100A1, NF-κB p65, and IL-6 levels between TIA and HC groups (all P > 0.05). S100A1, NF-κB p65, and IL-6 levels in the LCI group were (254.25 ± 37.07) ng/L, (4.41 ± 0.45) mg/L, and (14.00 ± 1.40) ng/L, respectively, which were significantly higher than (225.42 ± 30.92) ng/L, (3.85 ± 0.64) mg/L, (12.77 ± 1.31) ng/L in the MCI group ( t = 3.04, 3.60, 3.20, all P < 0.05) and (223.98 ± 40.21) ng/L, (3.88 ± 0.66) mg/L, (13.27 ± 1.65) ng/L in the SCI group ( t = 3.79, 4.01, 2.25, all P < 0.05). There were no significant differences in S100A1, NF-κB p65, and IL-6 levels between MCI and SCI groups (all P > 0.05). S100A1 and NF-κB p65 levels in patients with AICI were positively correlated with the volume of cerebral infarct ( r = 0.24, 0.27, both P < 0.05). S100A1 and IL-6 levels in patients with AICI were positively correlated with the National Institutes of Health Stroke Scale score ( r = 0.24, 0.28, both P < 0.05). The areas under the curves plotting S100A1, NF-κB p65, and IL-6 levels against AICI diagnosis were 0.818, 0.667 and 0.754, respectively. The optimal cutoff values were 181.03, 3.50 and 10.79, respectively. The corresponding sensitivities were 95.0%, 76.6% and 97.2%, respectively, and the specificities were 37.3%, 45.1% and 49.0%, respectively. Conclusion:Increased S100A1, NF-κB p65, and IL-6 levels in patients with AICI are closely related to the severity of AICI.

Effect of melatonin on peripheral nerve damage resulting from tibial defect in rats / Efecto de la melatonina sobre el daño de los nervios periféricos como resultado de un defecto tibial en ratas

SUMMARY: Peripheral nerve damage (PNI) can cause demyelination, axonal degeneration and loss of motor and sensory function. Melatonin with its antioxidative effect, has been reported to reduce scar formation in nerve injury, take a role in repair process by suppressing fibroblast proliferation in the damaged area. It was aimed to investigate the effect of melatonin in the repair of peripheral nerve damage and the relationship between S100 proteins and angiogenic regulation. Wistar albino rats were divided into 3 groups. In the Defect group, 6 mm tibial bone defect using a motorized drill was created and kept immobile for 28 days. In Defect + graft group, tibial bone defect with allograft treatment was applied and kept immobile for 28 days. In Defect + graft + Melatonin group, melatonin was administered to defect + allograft group. All rats were sacrified by decapitation, skin and tibia bone were removed then fixed with 10 % neutral buffered formalin and embedded in paraffin, sections were examined under light microscopy. In the Defect+Graft group, enlargement and occlusion of the vessels with degeneration of the epineural sheath, thickening of the endoneural sheath and mild hyperplasia of schwannocytus (Schwann cells) were remarkable. In the Defect+Graft+Melatonin group, the epineural sheath was tight and regular, the axonal structures were prominent in the endoneural area. Mild S100 expression was observed in Defect+Graft group in fibers of the endoneural region with a prominent expression in schwannocytus. In Defect+Graft+Melatonin group (10mg/kg), S100 expression was moderate in areas where schwannocytus proliferated and nerve-connective tissue sheaths were reconstructed. VEGF expression was moderate in endoneural, perineural and epineural connective tissue sheaths in the Defect+Graft+Melatonin group, with negative expression in blood vessel endothelial cells, but with a positive expression in schwannocytus. We conclude that with the application of melatonin; oxidative stress decreases, schwannocytus proliferation increases, having positive influence on nerve repair with the regulation of S100 signaling and angiogenetic structuring.

RESUMEN: El daño a los nervios periféricos puede causar desmielinización, degeneración axonal y pérdida de la función motora y sensorial. Se ha informado que la melatonina, con su efecto antioxidante, reduce la formación de cicatrices en lesiones nerviosas y desempeña un papel en el proceso de reparación al suprimir la proliferación de fibroblastos en el área dañada. El objetivo de este trabajo fue investigar el efecto de la melatonina en la reparación del daño de los nervios periféricos y la relación entre las proteínas S100 y la regulación angiogénica. Ratas albinas Wistar se dividieron en 3 grupos. En el grupo Defecto, se creó un defecto óseo tibial de 6 mm con un taladro motorizado y se mantuvo inmóvil durante 28 días. En el grupo Defecto + injerto, se aplicó tratamiento de defecto óseo tibial con aloinjerto y se mantuvo inmóvil durante 28 días. En el grupo Defecto + injerto + Melatonina, se administró melatonina al grupo defecto + aloinjerto. Todas las ratas fueron sacrificadas por decapitación, se extrajo la piel y el hueso de la tibia y luego se fijaron con formalina tamponada neutra al 10 % y se incluyeron en parafina, las secciones se examinaron bajo microscopía óptica. En el grupo Defecto+Injerto, fueron notables el agrandamiento y la oclusión de los vasos con degeneración de la vaina epineural, engrosamiento de la vaina endoneural e hiperplasia leve de los schwannocitos (neurolemnocitos). En el grupo Defecto+Injerto+Melatonina, la vaina epineural era estrecha y regular, las estructuras axonales eran prominentes en el área endoneural. Se observó expresión leve de S100 en el grupo Defecto+Injerto en fibras de la región endoneural con una expresión prominente en los schwannocitos. En el grupo Defecto+Injerto+Melatonina, la expresión de S100 fue moderada en áreas donde proliferaron los schwannocitos y se reconstruyeron las vainas de tejido conectivo nervioso. La expresión de VEGF fue moderada en vainas de tejido conectivo endoneural, perineural y epineural en el grupo Defecto+Injerto+Melatonina, con expresión negativa en células endoteliales de vasos sanguíneos, pero con expresión positiva en schwannocitos. Concluimos que con la aplicación de melatonina; disminuye el estrés oxidativo, aumenta la proliferación de schwannocitos, influyendo positivamente en la reparación nerviosa con la regulación de la señalización S100 y la estructuración angiogenética.

Why human prepuce is a valuable resource in science? Histological, ultrastructural, immunohistochemical and statistical analysis / ¿Por qué el prepucio humano es un recurso valioso en la ciencia? Análisis histológicos, ultraestructurales, inmunohistoquímicos y estadísticos

SUMMARY: This research was to examine the histological and ultrastructural characteristics of prepuce samples, as well as vimentin and S100 protein localization and statistical analysis. Urologists have long struggled with the prepuce, which is used to treat a variety of urethral problems. Skin biopsies were collected from the prepuce at the moment of circumcision and processed for light microscopy, electron microscope examination, immunohistochemical techniques, and statistical analysis in a total of six boys. Histologically, the prepuce epidermis displayed focal spiky ridges, which are saw-toothed interspersed with sulci, slight hyperpigmentation, looser connective tissue and plentiful vascular components. Immunohistochemically, the existence of melanocytes and Langerhans cells in the epidermis, as well as smooth muscles in the dermis, was stained positively for vimentin. Also, there was a positive reactivity of the Langerhans cells in the epidermis and around Meissner's corpuscles in the dermis for S100 protein staining. Ultrastructurally, the prepuce's intercellular gaps were widened, melanocytes rested on a folded basement membrane, and desmosomal content was reduced, with a prominent active euchromatic nucleus. Cytoplasmic projections were distended and elongated, and the interstitial blood vessels were surrounded by endothelial cells and rested on a basement membrane. There were also minimal collagen fibers in the interstitium. The prepuce's histological and ultrastructural features, as well as immunohistological studies using vimentin and S100 protein as intermediate filaments and statistical analysis, all demonstrated that it is a useful scientific resource.

RESUMEN: El presente trabajo de investigación se realizó para examinar las características histológicas y ultraestructurales de las muestras de prepucio, así como la localización y el análisis estadístico de la vimentina y la proteína S100. Los urólogos han intentado trabajar durante mucho tiempo con el prepucio, que se usa para tratar una variedad de problemas uretrales. Se recolectaron biopsias de piel del prepucio de seis niños en el momento de la circuncisión y se procesaron para microscopía óptica, examen con microscopio electrónico, técnicas inmunohistoquímicas y análisis estadístico. Histológicamente, la epidermis del prepucio mostraba crestas puntiagudas focales, intercaladas con surcos, hiperpigmentación leve, tejido conectivo más laxo y abundantes componentes vasculares. Inmunohistoquímicamente, la existencia de melanocitos y células dendríticas epidérmicas (células de Langerhans), así como músculo liso en la dermis, se tiñeron positivamente para vimentina. Además, hubo una reactividad positiva de las células dendríticas epidérmicas en la epidermis y alrededor de los corpúsculos del tacto (de Meissner) en la dermis para la tinción de la proteína S100. Ultraestructuralmente, los espacios intercelulares del prepucio se ensancharon, los melanocitos descansaban sobre una membrana basal plegada y el contenido desmosómico se redujo, con un núcleo eucromático activo prominente. Las proyecciones citoplasmáticas estaban distendidas y alargadas, y los vasos sanguíneos intersticiales estaban rodeados por células endoteliales y descansaban sobre una membrana basal. También había fibras de colágeno mínimas en el intersticio. Las características histológicas y ultraestructurales del prepucio, así como los estudios inmunohistológicos utilizando vimentina y proteína S100 como filamentos intermedios y el análisis estadístico, demostraron que es un recurso científico útil.

Dysfunctional eating behavior in fibromyalgia and its association with serum biomarkers of brain plasticity (BDNF and S100B): an exploratory study

ABSTRACT Objectives: To assess disordered eating, hunger and satiety perceptions in women with fibromyalgia (FM) compared to healthy controls (HC) and their association with biomarkers of brain plasticity (brain-derived neurotrophic factor (BDNF) and S100 calcium-binding protein B (S100B)). Subjects and methods: Cross-sectional exploratory study. The sample included FM (n = 20) and HC (n = 19), matched to age and waist perimeter. Dysfunctional eating was assessed through the Three Factor Eating Questionnaire and Eating Disorders Examination with a questionnaire. Hunger and satiety levels were rated by a Numerical Scale. Serum leptin, S100B and BDNF were analyzed. Results: The MANCOVA analysis showed that the mean of Emotional Eating rates was 30.65% higher in FM compared to HC ( p = 0.015). Eating, shape and weight concerns were 77.77%, 57.14% and 52.22% higher in FM ( p = <0.001) compared to HC, respectively. Moreover, the FM group reported higher scores for feeling of hunger "[5.2 (±2.9) vs. 4.8 (±2.0); p = 0.042] and lower scores for satiety [7.0 (±1.7) vs . 8.3 (±1.0); p = 0.038]. In the FM group, serum BDNF was negatively associated with hunger (r = - 0.52; p = 0.02), while S100B was positively associated with hunger scores (r = 0.463; p = 0.004). Conclusion: The present findings support the hypothesis that the association between FM and obesity can be mediated by a hedonistic pathway. Further research is needed.

Case for diagnosis. Dorsal nodule in a 10-year-old male

Abstract Granular cell tumors (GCTs) are rare soft-tissue neoplasms. GCT immunohistochemistry is positive for S-100, NSE, and CD68. This report describes the case of a 10-year-old male who presented with a dorsal nodule. A biopsy revealed aggregates and sheets of large epithelioid and spindle cells. The cells had abundant eosinophilic granular cytoplasm. Immunohistochemical analysis was positive for CD68, NKI/C3, and synaptophysin; weakly positive for NSE; and negative for S-100, SOX10, HMB45, Melan A, cytokeratin, SMA, EMA, and CD163. The Ki-67 index was less than 1%. A diagnosis of an S-100 negative, cutaneous, benign GCT was determined.

Levels of the interleukins 17A, 22, and 23 and the S100 protein family in the gingival crevicular fluid of psoriatic patients with or without periodontitis,

Abstract Background: Psoriasis and periodontitis are immunologically mediated chronic inflammatory diseases. Epidemiologic evidence has linked both; however, the change of markers in gingival crevicular fluid has been poorly evaluated. Objective: To evaluate the levels of IL-17A, IL-22, IL-23, S100A7, S100A8, and S100A9 in gingival crevicular fluid of psoriatic and healthy subjects with and without periodontitis and their relations to psoriasis severity. Methods: Cross-sectional study. Sample comprised the following groups: healthy controls without periodontitis or with mild periodontitis (n = 21), healthy controls with moderate or severe periodontitis (n = 18), individuals with psoriasis without or mild periodontitis (n = 11), and individuals with psoriasis and moderate or severe periodontitis (n = 32). Levels of IL-17A, IL-22, IL-23, S100A8, and S100A9 were determined by multiplex assay and S100A7 was measured by ELISA. Results: No inter-group differences in the levels of IL-17A, IL-22, IL-23, and S100A7 were found. S100A8 levels were higher in psoriatic patients than controls (p < 0.05). S100A8 was positively correlated with psoriasis severity in the group with psoriasis (p < 0.05). S100A9 exceeded the detection limits. Study limitations: This pilot study presents a small sample size. Conclusions: The concentrations of S100A8 were highest in psoriatic patients regardless of periodontal health/status. S100A8 was associated with the severity of psoriasis. The concentrations of interleukins and S100A7 were similar in psoriatic patients with or without periodontitis vs. healthy controls.