1.Brain injury biomarkers and applications in neurological diseases.
Han ZHANG ; Jing WANG ; Yang QU ; Yi YANG ; Zhen-Ni GUO
Chinese Medical Journal 2025;138(1):5-14
Neurological diseases are a major health concern, and brain injury is a typical pathological process in various neurological disorders. Different biomarkers in the blood or the cerebrospinal fluid are associated with specific physiological and pathological processes. They are vital in identifying, diagnosing, and treating brain injuries. In this review, we described biomarkers for neuronal cell body injury (neuron-specific enolase, ubiquitin C-terminal hydrolase-L1, αII-spectrin), axonal injury (neurofilament proteins, tau), astrocyte injury (S100β, glial fibrillary acidic protein), demyelination (myelin basic protein), autoantibodies, and other emerging biomarkers (extracellular vesicles, microRNAs). We aimed to summarize the applications of these biomarkers and their related interests and limits in the diagnosis and prognosis for neurological diseases, including traumatic brain injury, status epilepticus, stroke, Alzheimer's disease, and infection. In addition, a reasonable outlook for brain injury biomarkers as ideal detection tools for neurological diseases is presented.
Humans
;
Biomarkers/cerebrospinal fluid*
;
Nervous System Diseases/diagnosis*
;
Brain Injuries/metabolism*
;
Phosphopyruvate Hydratase/cerebrospinal fluid*
;
Glial Fibrillary Acidic Protein/blood*
;
S100 Calcium Binding Protein beta Subunit/blood*
;
tau Proteins/cerebrospinal fluid*
;
Ubiquitin Thiolesterase/blood*
;
Myelin Basic Protein/cerebrospinal fluid*
;
Neurofilament Proteins/blood*
;
MicroRNAs/blood*
;
Brain Injuries, Traumatic/metabolism*
2.Clinicopathological and immunohistochemical analysis of maxillofacial granular cell tumor.
Zeliang SHEN ; Lihong YAO ; Hongjie JIANG ; Mao LI ; Yaling TANG
West China Journal of Stomatology 2023;41(4):414-420
OBJECTIVES:
To analyze the clinicopathological features of maxillofacial granular cell tumors (GCT) with the aid of immunohistochemical staining.
METHODS:
Seven cases of maxillofacial GCT were retrospectively collated, and the microscopic morphology of maxillofacial GCT was analyzed. The expression of S-100, neuron-specific enolase (NSE), SOX-10, CD68, actin, desmin, and Ki-67 in GCT was detected by immunohistochemical staining. The cases were observed in the follow-ups after clinical treatment.
RESULTS:
All seven GCT tumors lacked envelopes and were poorly defined. Microscopically, the sizes of the tumor cells were large and appeared with inconspicuous cell membranes, forming a syncytium-like appearance. The cytoplasm was filled with characteristic eosinophilic granules. The immunohistochemical results showed that six cases were NSE-positive, five cases were S-100-positive, seven cases were CD68-positive, five cases were SOX-10-positive, one case was actin-positive, and seven cases were desmin-negative. The Ki-67 index did not exceed 5% in all cases. In the follow-up sessions, none of the six cases presented a recurrence.
CONCLUSIONS
Maxillofacial GCT has a characteristic histological structure. Immunohistochemical S-100, CD68, and other indicators can assist in diagnosis, and the prognosis is good after clinical resection.
Humans
;
Ki-67 Antigen/metabolism*
;
Granular Cell Tumor/surgery*
;
Retrospective Studies
;
Actins/metabolism*
;
Desmin/metabolism*
;
S100 Proteins/metabolism*
3.Clinicopathological features of olfactory carcinoma.
C C ZHANG ; H LI ; L Q CHENG ; H B WU
Chinese Journal of Pathology 2023;52(11):1138-1143
Objective: To investigate the clinicopathological features and differential diagnosis of olfactory carcinoma (OC). Methods: Twenty-one cases of sinonasal tumors, including those initially diagnosed as olfactory neuroblastoma (ONB) and those with uncertain diagnosis, were collected from the Department of Pathology, the First Affiliated Hospital of University of Science and Technology of China (Anhui Provincial Hospital) from January 2016 to August 2022, among which 3 cases were reclassified as OC. The clinicopathological features were investigated, and the remaining 18 cases were used as control. Results: Of the three OC patients, 2 were male and 1 was female, with an average age of 57 years ranging from 35 to 74 years. Microscopically, the tumor cells were arranged in solid, nested or lobulated patterns with occasional palisading around the solid nests. The stroma was highly vascular with focal neurofibrillary areas. There were prominent rosettes or pseudorosettes formation. The tumor cells were mainly ovoid to spindly with scant to moderate amount of cytoplasm, one or several small nucleoli, and fine chromatin content. Brisk mitotic figures were seen. In all 3 cases of OC, there were scanty atypical glands and some were ciliated. Immunohistochemically, at least one epithelial marker and neuroendocrine marker were diffusely expressed in the tumor. Some of the tumor cells were positive for p40 and p63, and the sustentacular cells showed the expression of S-100 protein. All cases tested were negative for NUT, CD99 and desmin, with intact expression of SMARCA4 (BRG1) and SMARCB1 (INI-1). Ki-67 proliferation index varied from 20% to 80%. Follow-up after 16-18 months showed no mortality with tumor recurrence from 1 patient after 16 months. Conclusion: OC is a rare sinonasal tumor with neuroepithelial differentiation, its histomorphology is diverse, and the combination of immunohistochemical markers is essential for appropriate diagnosis.
Humans
;
Male
;
Female
;
Middle Aged
;
Paranasal Sinus Neoplasms/chemistry*
;
Biomarkers, Tumor/metabolism*
;
Carcinoma/chemistry*
;
Diagnosis, Differential
;
S100 Proteins
;
DNA Helicases/metabolism*
;
Nuclear Proteins/metabolism*
;
Transcription Factors/metabolism*
4.S100 calcium binding protein A16 promotes fat synthesis through endoplasmic reticulum stress in HepG2 cells.
Jing-Bao KAN ; Ge-Qian SHEN ; Jie YANG ; Pei TONG ; Ri-Hua ZHANG ; Xiu-Bin LIANG ; Dong-Ming SU ; Dong LI ; Yun LIU
Acta Physiologica Sinica 2019;71(2):279-286
The aim of this study was to investigate the role of S100 calcium binding protein A16 (S100A16) in lipid metabolism in hepatocytes and its possible biological mechanism. HepG2 cells (human hepatoma cell line) were cultured with fatty acid to establish fatty acid culture model. The control model was cultured without fatty acid. Each model was divided into three groups and transfected with S100a16 over-expression, shRNA and vector plasmids, respectively. The concentration of triglyceride (TG) in the cells was measured by kit, and the lipid droplets was observed by oil red O staining. Immunoprecipitation and mass spectrometry were used to find the interesting proteins interacting with S100A16, and the interaction was verified by immunoprecipitation. The further mechanism was studied by Western blot and qRT-PCR. The results showed that the intracellular lipid droplet and TG concentrations in the fatty acid culture model were significantly higher than those in the control model. The accumulation of intracellular fat in the S100a16 over-expression group was significantly higher than that in the vector plasmid transfection group. There was an interaction between heat shock protein A5 (HSPA5) and S100A16. Over-expression of S100A16 up-regulated protein expression levels of HSPA5, inositol-requiring enzyme 1α (IRE1α) and pIREα1, which belong to endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway. Meanwhile, over-expression of S100A16 up-regulated the mRNA expression levels of adipose synthesis-related gene Srebp1c, Acc and Fas. In the S100a16 shRNA plasmid transfection group, the above-mentioned protein and mRNA levels were lower than those of vector plasmid transfection group. These results suggest that S100A16 may promote lipid synthesis in HepG2 cells through endoplasmic reticulum stress HSPA5/IRE1α-XBP1 pathway.
Endoplasmic Reticulum Stress
;
Endoribonucleases
;
physiology
;
Heat-Shock Proteins
;
physiology
;
Hep G2 Cells
;
Humans
;
Lipid Metabolism
;
Protein-Serine-Threonine Kinases
;
physiology
;
S100 Proteins
;
physiology
;
Triglycerides
;
biosynthesis
;
X-Box Binding Protein 1
;
physiology
5.Pleomorphic adenoma of the nasal septum: a case report.
Jing LI ; Di BIAN ; Jianyan WANG
Journal of Clinical Otorhinolaryngology Head and Neck Surgery 2016;30(1):76-77
We report a rare case of pleomorphic adenoma arising from the nasal septum. A 37-year-old woman presented with a 1-year-history of right-sided occasional epistaxis. Computed tomographic scans revealed an oval mass in the right nasal cavity. The tumor was removed endoscopically with endonasal approach. The microscopic finding showed numbers of myoepithelial cells and duct-like structures consisting of loose myxoid stroma. This lesion had histological characteristics of a pleomorphic adenoma, and this was confirmed by immunohistochemical expression of cytokeratin, S-100 protein and SMA. Her post-operative course was uneventful, and she is currently free from the disease 1.5 years after surgery.
Actins
;
metabolism
;
Adenoma, Pleomorphic
;
diagnosis
;
surgery
;
Adult
;
Endoscopy
;
Epistaxis
;
Epithelial Cells
;
Female
;
Humans
;
Keratins
;
metabolism
;
Nasal Septum
;
pathology
;
Nose Neoplasms
;
diagnosis
;
surgery
;
S100 Proteins
;
metabolism
6.Role of S100A4 in the epithelial-mesenchymal transition of esophageal squamous cell carcinoma and its molecular mechanism.
Liu JIAN ; Wang ZHIHONG ; Wang LIUXING ; Fan QINGXIA
Chinese Journal of Oncology 2015;37(4):258-265
OBJECTIVETo explore the role of S100A4 in the epithelial-mesenchymal transition (EMT) in esophageal squamous cell carcinoma and its possible molecular mechanism.
METHODSThree chemically synthesized S100A4 siRNA sequences were transiently transfected into esophageal carcinoma EC9706 cells. EC9706 cells transfected with negative siRNA, lipofectamine 2000, and vacant EC9706 cells were used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the inhibition rate of S100A4 siRNA. S100A4 siRNA2 with the best inhibition rate was chosen to transiently transfect into EC9706 cells under the same conditions. The EC9706 cells transfected with negative siRNA, lipofectamine 2000 and vacant EC9706 cells were also used as control. Fluorescence quantitative RT-PCR and Western blot were used to detect the mRNA and protein expressions of E-cadherin, vimentin and snail. The morphology of EC9706 cells was observed under an inverted microscope. Boyden chamber and scratch test were used to detect the invasion and migration ability of EC9706 cells, and CCK8 assay was used to detect the proliferation ability of EC9706 cells. EC9706 cells transfected with S100A4 siRNA2 were further transfected with snail eukaryotic expression vector. The EC9706 cells transfected with S100A4 siRNA, EC9706 cells transfected with snail eukaryotic expression vector and vacant EC9706 cells were used as control. The above indexes of all the groups were observed, too.
RESULTSThe S100A4 mRNA and protein expression levels of the S100A4 siRNA2 group were 0.417 ± 0.041 and 0.337 ± 0.039, the transmembrane cell number was 61.608 ± 8.937, the scratch healing distance was (0.216 ± 0.064) mm, the A value was 0.623 ± 0.084, the E-cadherin mRNA and protein levels were 0.619 ± 0.032 and 0.495 ± 0.034, the vimentin mRNA and protein levels were 0.514 ± 0.032 and 0.427 ± 0.028, the snail mRNA and protein levels were 0.573 ± 0.029 and 0.429 ± 0.041. These data were significantly different with the liposome group, the negative control group and the blank group (P < 0.05 for all). After the S100A4 siRNA2 treatment for 24 h, the appearance of EC9706 cells changed to epithelial cell morphology. The transmembrane cell number and the scratch healing distance of the S100A4 siRNA2+snail eukaryotic expression vector group were (69.382 ± 9.666) cells and (0.274 ± 0.029) mm, the A value was 0.823 ± 0.101, the snail mRNA and protein levels were 0.704 ± 0.037 and 0.625 ± 0.031, the vimentin mRNA and protein levels were 0.712 ± 0.046 and 0.609 ± 0.038, and these data were significantly higher than those of the Sl00A4 siRNA2 group (P < 0.05 for all). The E-cadherin mRNA and protein levels of the S100A4 siRNA2+eukaryotic expression vector group were 0.437 ± 0.038 and 0.381 ± 0.031, significantly lower than those of the S100A4 siRNA2 group (P < 0.05 for all). However, snail had no effect on the morphology of EC9706 cells.
CONCLUSIONSS100A4 may be involved in the EMT process of esophageal squamous-cell carcinoma by regulating the expression of snail and then plays a role in the invasion and metastasis of esophageal carcinoma.
Cadherins ; analysis ; Carcinoma, Squamous Cell ; metabolism ; pathology ; physiopathology ; Cell Line, Tumor ; Epithelial Cells ; Epithelial-Mesenchymal Transition ; Esophageal Neoplasms ; metabolism ; pathology ; physiopathology ; Humans ; Indicators and Reagents ; Lipids ; RNA, Messenger ; analysis ; RNA, Small Interfering ; analysis ; physiology ; S100 Calcium-Binding Protein A4 ; S100 Proteins ; antagonists & inhibitors ; genetics ; physiology ; Snail Family Transcription Factors ; Transcription Factors ; analysis ; genetics ; Transfection ; Vimentin ; analysis ; genetics
7.Diagnostic utility of S100A1, GLUT-1 and Caveolin-1 in renal tumors with oncocytic features: a comparative study.
Wei ZHANG ; Kejia WANG ; Wenjuan YU ; Yan LIU ; Jing CHU ; Yanxia JIANG ; Yujun LI ;
Chinese Journal of Pathology 2015;44(11):767-771
OBJECTIVETo study the immunohistochemical expression of S100A1, GLUT-1 and Cavolin-1 and its diagnostic significance in renal tumors with oncocytic features.
METHODSTissue microarray and immunohistochemical staining for S100A1, GLUT-1 and Cavolin-1 were carried out in 59 cases of renal tumors with oncocytic features, including 19 cases of renal oncocytoma, 15 cases of clear cell renal cell carcinoma (CCRCC) with eosinophilic cells, 11 cases of eosinophilic variant of chromophobe renal cell carcinoma, 7 cases of oncocytic papillary renal cell carcinoma and 7 cases of epithelioid angiomyolipoma.
RESULTSS100A1 was expressed in renal oncocytoma, with a positive propotion of 16/19 (including 14 cases showing widespread and strong positivity). On the other hand, the rate of expression of S100A1 was 2/11 in eosinophilic variant of chromophobe renal cell carcinoma, 10/15 in CCRCC with eosinophilic cells, 3/7 in oncocytic papillary renal cell carcinoma and 6/7 in epithelioid angiomyolipoma (P>0.05). The difference of S100A1 expression between renal oncocytoma and eosinophilic variant of chromophobe renal cell carcinoma was statistically significant. GLUT-1 was located in cell membrane, with a positive rate of 13/15 in CCRCC with eosinophilic cells, 7/19 in renal oncocytoma, 4/7 (weak) in oncocytic papillary renal cell carcinoma, 1/11 in eosinophilic variant of chromophobe renal cell carcinoma and 0/7 in epithelioid angiomyolipoma. The rate of expression of Cav-1 was 6/15 in CCRCC with eosinophilic cells, 2/7 in oncocytic papillary renal cell carcinoma, 5/7 in epithelioid angiomyolipoma, 2/11 (weak) in eosinophilic variant of chromophobe renal cell carcinoma and 0/19 in renal oncocytoma. S100A1 showed high sensitivity and 50% specificity in the diagnosis of renal oncocytoma. GLUT-1 and Cav-1 showed high specificity and sensitivity in the diagnosis of CCRCC and epithelioid angiomyolipoma.
CONCLUSIONSS100A1 is widely expressed in various oncocytic renal neoplasms and helpful in differential diagnosis of renal oncocytoma from eosinophilic variant of chromophobe renal cell carcinoma, but not from other 3 oncocytic renal tumors. Overexpression of GLUT-1 can be used in distinction between CCRCC and renal oncocytoma. Cav-1 is widely expressed in CCRCC and epithelioid angiomyolipoma but not in renal oncocytoma. Cav-1 expression thus rules out renal oncocytoma.
Adenoma, Oxyphilic ; diagnosis ; metabolism ; Angiomyolipoma ; diagnosis ; metabolism ; Biomarkers, Tumor ; metabolism ; Carcinoma, Renal Cell ; diagnosis ; metabolism ; Caveolin 1 ; metabolism ; Diagnosis, Differential ; Glucose Transporter Type 1 ; metabolism ; Humans ; Immunohistochemistry ; Kidney Neoplasms ; diagnosis ; metabolism ; S100 Proteins ; metabolism ; Sensitivity and Specificity
8.Granular Cell Tumors on Unusual Anatomic Locations.
Yonsei Medical Journal 2015;56(6):1731-1734
Granular cell tumors (GCTs) are soft tissue tumors, which are thought to be derived from Schwann cells. Although most GCTs are reported to arise in tongue and oral cavity (30-50%), they can appear on any anatomic sites, even visceral organs. Herein, we report 5 cases of GCTs on unusual anatomic locations, such as palm, arm, thigh, finger, and vulvar area. Complete surgical excision is preferred treatment of choice to prevent recurrence. These cases emphasize that GCTs not involving oral cavity are more prevalent than expected, and the diagnosis should be histopathologically confirmed.
Adult
;
Aged
;
Biopsy
;
Child
;
Female
;
Granular Cell Tumor/metabolism/*pathology/surgery
;
Hand
;
Humans
;
Immunohistochemistry
;
Middle Aged
;
Mohs Surgery
;
Neoplasm Recurrence, Local/*prevention & control
;
S100 Proteins/analysis/metabolism
;
Treatment Outcome
9.Diffuse Ganglioneuromatosis of the Colon Presenting as a Large Subepithelial Tumor in Adults: Report of Two Cases.
Tae Jun KIM ; Hyun LIM ; Ho Suk KANG ; Sung Hoon MOON ; Jong Hyeok KIM ; Choong Kee PARK ; Mi Jung KWON ; Bong Hwa LEE
The Korean Journal of Gastroenterology 2015;66(2):111-115
Colonic diffuse ganglioneuromatosis is a benign neoplastic condition characterized by disseminated, intramural, or transmural proliferation of neural elements involving the enteric plexuses, sometimes associated with von Recklinghausen's disease and other multiple tumor syndromes. Colonic diffuse ganglioneuromatosis is usually large, ranging from 1 to 17 cm, and thus can distort the surrounding tissue architecture as well as infiltrate the adjacent bowel wall. However, colonic diffuse ganglioneuromatosis is an exceptional finding in adults and only individual cases are reported in the literature. Herein, we report two unusual cases of adult patients with colonic diffuse transmural ganglioneuromatosis presenting as a large subepithelial tumor.
Adult
;
Aged
;
Colon/metabolism/*pathology
;
Colonoscopy
;
Ganglioneuroma/*diagnosis/metabolism/pathology
;
Humans
;
Immunohistochemistry
;
Male
;
S100 Proteins/metabolism
;
Tomography, X-Ray Computed
10.Expression of S100B and GFAP after primary brainstem injury in rat.
Yu-Hong WU ; Hui-Jun WANG ; Xin WANG
Journal of Forensic Medicine 2015;31(1):11-14
OBJECTIVE:
To study the expression of S100B and glial tibrillory acidic protein (GFAP) atter primary brainstem injury in rat and discuss the changes with brainstern injury time and their mechanism in the injury.
METHODS:
The brainstem injury animal model was established using the mechanical impacting method. The HE staining, Gless argentaffin staining and SP immunohistochemical method were applied to observe the changes of S100B and GFAP at different injury time. The immunostaining results were measured statistically with imaging analysis technology.
RESULTS:
A large number of S100B positive cells could be seen in 30 min. Afterward, expression increased gradually with time and peaked up in 24 h, and reversed back the normal in 72h. The GFAP positive cells showed rise continually in 30 min, and reached the peak in 48 h, then started to decrease, but still higher than that in control.
CONCLUSION
The expression of S100B and GFAP is correlated with post traumatic intervals after brainstem injury in rat, and may be useful in estimation post traumatic intervals and nerve regeneration.
Animals
;
Brain Injuries/metabolism*
;
Brain Stem/metabolism*
;
Disease Models, Animal
;
Glial Fibrillary Acidic Protein/metabolism*
;
Immunohistochemistry
;
Nerve Growth Factors
;
Neuroglia
;
Rats
;
S100 Calcium Binding Protein beta Subunit/metabolism*
;
S100 Proteins

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