S100 proteins and their implication in the thalamus: an integrative review / Las proteínas S100 y su implicación en el tálamo: una revisión integradora

SUMMARY: S100 proteins belong group of calcium-binding proteins and are present in physiological intracellular and extracellular regulatory activities, such as cell differentiation, and act in inflammatory and neoplastic pathological processes. Recently, its expressions in the nervous system have been extensively studied, seeking to elucidate its action at the level of the thalamus: A structure of the central nervous system that is part of important circuits, such as somatosensory, behavioral, memory and cognitive, as well as being responsible for the transmission and regulation of information to the cerebral cortex. This article is an integrative review of scientific literature, which analyzed 12 studies present in Pubmed. The analysis showed that the relationship of S100 proteins and the thalamus has been described in neoplastic processes, mental disorders, hypoxia, trauma, stress, infection, Parkinson's disease and epilepsy. In summary, it is possible to conclude that this protein family is relevant as a marker in processes of thalamic injury, requiring further studies to better understand its clinical, preclinical meanings and its prognostic value.

Las proteínas S100 pertenecen al grupo de proteínas fijadoras de calcio y están presentes en actividades reguladoras fisiológicas intracelulares y extracelulares, como la diferenciación celular, y actúan en procesos patológicos inflamatorios y neoplásicos. Recientemente, sus expresiones en el sistema nervioso han sido ampliamente estudiadas, buscando dilucidar su acción a nivel del tálamo: una estructura del sistema nervioso central que forma parte de importantes circuitos, como el somatosensorial, conductual, de memoria y cognitivo, así como además de ser responsable de la transmisión y regulación de la información a la corteza cerebral. Este artículo es una revisión integradora de la literatura científica, que analizó 12 estudios presentes en Pubmed. El análisis mostró que la relación de las proteínas S100 y el tálamo ha sido descrita en procesos neoplásicos, trastornos mentales, hipoxia, trauma, estrés, infección, enfermedad de Parkinson y epilepsia. En resumen, es posible concluir que esta familia de proteínas es relevante como marcador en procesos de lesión talámica, requiriendo más estudios para comprender mejor su significado clínico, preclínico y su valor pronóstico.

A case of neonatal-onset autoinflammation with infantile enterocolitis caused by a de novoNLRC4 gene variation / 中华围产医学杂志

This article reported a case of neonatal-onset autoinflammation with infantile enterocolitis (AIFEC) caused by NLRC4 gene mutation. The boy developed the disease in the neonatal period, presenting with recurrent fever, rash, hepatosplenomegaly and enterocolitis. Laboratory tests showed some indicators including ferritin and C-reactive protein were elevated. His condition was complicated by macrophage activation syndrome and anti-infective treatment was ineffective. High-throughput whole exome sequencing revealed a de novo heterozygous mutation of c.1021G>C (p.Val341Leu) in the NLRC4 gene and AIFEC was confirmed. AIFEC is a rare disease with no effective treatment at present, which can be developed in the neonatal period and diagnosed by whole exome sequencing.

Revealing the Precise Role of Calretinin Neurons in Epilepsy: We Are on the Way / 神经科学通报·英文版

Epilepsy is a common neurological disorder characterized by hyperexcitability in the brain. Its pathogenesis is classically associated with an imbalance of excitatory and inhibitory neurons. Calretinin (CR) is one of the three major types of calcium-binding proteins present in inhibitory GABAergic neurons. The functions of CR and its role in neural excitability are still unknown. Recent data suggest that CR neurons have diverse neurotransmitters, morphologies, distributions, and functions in different brain regions across various species. Notably, CR neurons in the hippocampus, amygdala, neocortex, and thalamus are extremely susceptible to excitotoxicity in the epileptic brain, but the causal relationship is unknown. In this review, we focus on the heterogeneous functions of CR neurons in different brain regions and their relationship with neural excitability and epilepsy. Importantly, we provide perspectives on future investigations of the role of CR neurons in epilepsy.

Expression of calcium-binding protein 39 and vascular endothelial growth factor in bladder cancer and their effect on prognosis / 中国医师杂志

Objective:To explore the expression of calcium-binding protein 39 (CAB39) and vascular endothelial growth factor (VEGF) in bladder cancer tissues and their relationship with the prognosis of patients.Methods:A case-control study was conducted to select the focal tissues (case group) and post-operative paracancourous tissues (control group) from 94 bladder cancer patients who underwent surgery from Zibo Central Hospital from June 2014 to April 2018. Western blot and immunohistochemical staining were used to detect the expression of VEGF and CAB39 proteins in the two specimens. The positive expression rates of VEGF and CAB39 protein in bladder cancer tissues with different pathological characteristics were analyzed, and the relationship between VEGF and CAB39 protein expression and prognosis of patients with bladder cancer was analyzed by Cox proportional hazard regression model.Results:The relative expression levels of VEGF and CAB39 protein in the case group were significantly higher than those in the control group, with significant statistical difference (all P<0.05). The immunohistochemical staining scores of VEGF and CAB39 protein in the case group were higher than those in the control group, with statistically significant difference (all P<0.05). The positive expression rate of CAB39 protein was significantly higher in bladder cancer tissure of patients with low-grade, clinical stage T3-T4 and lymph node metastasis, with statistically significant difference (all P<0.05). The positive expression rate of VEGF protein was significantly higher in bladder cancer tissue of patients with clinical stage T3-T4 and lymph node metastasis, with statistically significant difference (all P<0.05). Cox proportional hazard regression model showed that low grade, clinical stage T3-T4, lymph node metastasis, positive expression of VEGF and CAB39 protein were independent risk factors for poor prognosis in bladder cancer patients in 3 years (all P<0.05). Conclusions:VEGF and CAB39 proteins are highly expressed in bladder cancer tissue, and have a certain relationship with the poor prognosis of patients.

Regulation of LncRNA00067110 on Proliferation, Apoptosis and Melanins Production of B16-F10 Cells by Targeting Cabyr / 中国生物化学与分子生物学报

Long non-coding RNA (lncRNA) is a type of non-coding RNA with the more than 200 nucleotides. Several lncRNAs have been identified as the potential targets for cancer therapy. LncRNA00067110 is one of the differentially expressed genes in the transcriptome profiles of melanoma B16-F10 cells compared to normal mice melanocytes. To investigate whether lncRNA00067110 regulates the proliferation, apoptosis and melanogenesis of B16-F10 cells, the calcium-binding tyrosine phosphorylation regulated protein (Cabyr) target gene was predicted by LncTar and verified by dual luciferase activities. The regulating function of lncRNA00067110 was investigated by the analysis of transcriptome profiles and to detect the proliferation, apoptosis and melanin production of B16-F10 cells transfected by the overexpression plasmids of lncRNA00067110. The results showed that the relationship of lncRNA00067110 targeting Cabyr, the mRNA and protein levels of proliferation (MEK/ERK/MNK/CREB) and melanogenesis-related genes (TYR family and CREB) were significantly down-regulated, while the mRNA and protein levels of apoptosis-related genes (AKT and Bcl-2) were up-regulated in B16-F10 cells with lncRNA00067110 overexpression. The transcriptome profile of B16-F10 cells with lncRNA00067110 overexpression showed that 17 genes were differentially expressed, among which Cabyr was up-regulated. Furthermore, the effect of lncRNA00067110 on the phenotypes of cell proliferation and apoptosis were verified. The results suggested that lncRNA00067110 might be a novel target for the treatment of melanoma by targeting Cabyr, which regulate the expression of related genes to inhibit the proliferation and melanogenesis, as well as to induce the apoptosis of B16-F10 cells.

Immunolocalización de s100a4 y α-sma en tejidos gingivales de pacientes con hipertrofia gingival por tratamiento ortodóntico: estudio preliminar / Immunolocalization of s100a4 and α-sma in gingival tissues of patients with gingival hypertrophy due to orthodontic treatment: preliminary study

Objective: to determine the presence and distribution of markers of the epithelialmesenchymal transition (EMT) (S-100A4 and alpha-smooth muscle actin-α-SMA) in gingival tissues of patients affected by Gingival hypertrophy (GH) due to orthodontics.GH is an exaggerated increase in gingival tissue whose pathogenesis is unknown. However, it has been reported that the epithelial-mesenchymal transition as a process involved in other types of GH. Materials and methods: descriptive study that included the analysis of gingival tissues of healthy individuals (n = 6) and patients with GH by orthodontic treatment (n = 6). Before gingival surgery, the patients underwent a periodontal hygiene phase. The gingival tissue samples obtained were processed and embedded in paraffin. The cuts were made with a microtome and deposited on polysine adhesion slides. Histological hematoxylin-eosin staining was performed.The identification and location of S-100A4 and α-SMA markers was determined by immunohistochemistry with monoclonal antibodies. The reading of the findings was carried out by oral pathologists. Results: in healthy individuals, an S100A4 label was observed in Langerhans cells, while α-SMA was identified in the vascular endothelium of all samples analysed. However, in patients with GH due to orthodontics, they registered an intense staining of S100A4 in gingival fibroblasts, Langerhans cells, vascular endothelium, and areas adjacent to the rupture of blood vessel. α-SMA expression in GO was detected in the vascular endothelium and gingival fibroblasts. Conclusion: the differential immunostaining of EMT markers in gingival tissues of patients with orthodontic GH suggests an eventual role of EMT in the pathogenesis of this pathology..Au

Objective: to determine the presence and distribution of markers of the epithelialmesenchymal transition (EMT) (S-100A4 and alpha-smooth muscle actin-α-SMA) in gingival tissues of patients affected by Gingival hypertrophy (GH) due to orthodontics. GH is an exaggerated increase in gingival tissue whose pathogenesis is unknown. However, it has been reported that the epithelial-mesenchymal transition as a process involved in other types of GH. Materials and methods: descriptive study that included the analysis of gingival tissues of healthy individuals (n = 6) and patients with GH by orthodontic treatment (n = 6). Before gingival surgery, the patients underwent a periodontal hygiene phase. The gingival tissue samples obtained were processed and embedded in paraffin. The cuts were made with a microtome and deposited on polysine adhesion slides. Histological hematoxylin-eosin staining was performed. The identification and location of S-100A4 and α-SMA markers was determined by immunohistochemistry with monoclonal antibodies. The reading of the findings was carried out by oral pathologists. Results: in healthy individuals, an S100A4 label was observed in Langerhans cells, while α-SMA was identified in the vascular endothelium of all samples analysed. However, in patients with GH due to orthodontics, they registered an intense staining of S100A4 in gingival fibroblasts, Langerhans cells, vascular endothelium, and areas adjacent to the rupture of blood vessel. α-SMA expression in GO was detected in the vascular endothelium and gingival fibroblasts. Conclusion: the differential immunostaining of EMT markers in gingival tissues of patients with orthodontic GH suggests an eventual role of EMT in the pathogenesis of this pathology..Au

Mechanisms of propofol-caused cognitive impairment in young obese rats / 第二军医大学学报

Objective To investigate the effect of propofol on cognitive function in young obese rats, and to explore its relationship with heme oxygenase 1 (HO-1), superoxide dismutase 1 (SOD1) protein expression and plasma S100 calciumbinding protein β (S100β) expression. Methods A total of 140 male SD rats aged 21 days were randomly divided into normal diet group (n=40) and high-fat diet group (n=100), and the rats were fed with a normal diet and a high-fat diet, respectively. After 4 weeks of feeding, 40 rats of the high-fat diet group with body mass≥the average body mass ≥1.4 times of the standard deviation of the normal diet group were designated as obese rats. The rats in the normal diet group were randomly divided into the normal lipid emulsion solvent group (NL group) and the normal propofol group (NP group), and the 40 obese rats were randomly divided into the obese lipid emulsion solvent group (OL group) and the obese propofol group (OP group), with 20 rats in each group. The rats in the propofol groups were intraperitoneally given propofol 100 mg/kg, and those in the lipid emulsion solvent groups (control groups) were intraperitoneally given lipid emulsion solvent 100 mg/kg, once a day for 7 days. On the first day after drug withdrawal, Morris water maze test was performed to evaluate the spatial learning and memory abilities of rats in each group. Meanwhile, the plasma S100β protein content of each group was detected by enzyme-linked immunosorbent assay, the expression levels of HO-1 and SOD1 protein in hippocampus were detected by Western blotting, and the changes of neurons in hippocampus CA1 area were observed by hematoxylin-eosin staining. Results Compared with the OL group, the escape latency time was significantly prolonged on 1-5 days (all P0.05). Conclusion Propofol can down-regulate the expression of anti-oxidant factors HO-1 and SOD1 in the hippocampus of young obese rats, leading to increase of S100β expression and oxidative stress and eventually causing cognitive impairment..

Effect of Zuoguiwan on Expression of Ca2+ Transport Pathway-related Protein in Ovariectomized Rats / 中国实验方剂学杂志

Objective::To explore the effect of Zuoguiwan on the bone mineral density (BMD) and the expressions of Ca2+ transport-associated protein in ovariectomized rats. Method::The 48 female SD rats were randomly divided into six groups: normal group, model group, sham operation group, estrogen group(0.167 mg·kg-1) and low and high-dose Zuoguiwan groups(9.6, 38.4 g·kg-1), with 10 rats in each group. Except for the sham-operated group, the ovariectomized rats in the other groups received the bilateral ovariectomy. Therapeutic intervention was given in each group for 3 months after the establishment of the model. After 12 weeks, BMD was measured using dualenergy X-ray absorptiometry. Tartrated presistant acid phosphatse(TRACP) and serum calcium were detected by biochemical kits.Protein expression in Ca2+ transport (Bone tissue) was detected by Western blot. Result::Compared with the normal group, the serum calcium of the model group was decreased(P<0.01). Compared with the normal group, BMD of the model group was decreased (P<0.01). The serum calcium of rats in high-dose group and western medicine group was higher than that of model group(P<0.01). BMD in model group was lower than that of Zuoguiwan groups and estrogen group(P<0.05). There was no significant difference in TRACP among the groups. Nilestriol and Zuoguiwan can down-regulate the expressions of TRPV5, NCX1, CaBP-D28K and PMCA1b in bone tissue of castrated rats(P<0.05, P<0.01). Conclusion::Zuoguiwan can down-regulate the expressions of Ca2+ transport-associated proteins (Bone tissues) in rat osteoclasts, with an efficacy on osteoporosis.

Effects of calcium-binding sites in the S2–S3 loop on human and Nematostella vectensis TRPM2 channel gating processes / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

As a crucial signaling molecule, calcium plays a critical role in many physiological and pathological processes by regulating ion channel activity. Recently, one study resolved the structure of the transient receptor potential melastatin 2 (TRPM2) channel from Nematostella vectensis (nvTRPM2). This identified a calcium-binding site in the S2–S3 loop, while its effect on channel gating remains unclear. Here, we investigated the role of this calcium-binding site in both nvTRPM2 and human TRPM2 (hTRPM2) by mutagenesis and patch-clamp recording. Unlike hTRPM2, nvTRPM2 cannot be activated by calcium alone. Moreover, the inactivation rate of nvTRPM2 was decreased as intracellular calcium concentration was increased. In addition, our results showed that the four key residues in the calcium-binding site of S2–S3 loop have similar effects on the gating processes of nvTRPM2 and hTRPM2. Among them, the mutations at negatively charged residues (glutamate and aspartate) substantially decreased the currents of nvTRPM2 and hTRPM2. This suggests that these sites are essential for calcium-dependent channel gating. For the charge-neutralizing residues (glutamine and asparagine) in the calcium-binding site, our data showed that glutamine mutating to alanine or glutamate did not affect the channel activity, but glutamine mutating to lysine caused loss of function. Asparagine mutating to aspartate still remained functional, while asparagine mutating to alanine or lysine led to little channel activity. These results suggest that the side chain of glutamine has a less contribution to channel gating than does asparagine. However, our data indicated that both glutamine mutating to alanine or glutamate and asparagine mutating to aspartate accelerated the channel inactivation rate, suggesting that the calcium-binding site in the S2–S3 loop is important for calcium-dependent channel inactivation. Taken together, our results uncovered the effect of four key residues in the S2–S3 loop of TRPM2 on the TRPM2 gating process.

Effects of calcium-binding sites in the S2-S3 loop on human and Nematostella vectensis TRPM2 channel gating processes / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

As a crucial signaling molecule, calcium plays a critical role in many physiological and pathological processes by regulating ion channel activity. Recently, one study resolved the structure of the transient receptor potential melastatin 2 (TRPM2) channel from Nematostella vectensis (nvTRPM2). This identified a calcium-binding site in the S2-S3 loop, while its effect on channel gating remains unclear. Here, we investigated the role of this calcium-binding site in both nvTRPM2 and human TRPM2 (hTRPM2) by mutagenesis and patch-clamp recording. Unlike hTRPM2, nvTRPM2 cannot be activated by calcium alone. Moreover, the inactivation rate of nvTRPM2 was decreased as intracellular calcium concentration was increased. In addition, our results showed that the four key residues in the calcium-binding site of S2-S3 loop have similar effects on the gating processes of nvTRPM2 and hTRPM2. Among them, the mutations at negatively charged residues (glutamate and aspartate) substantially decreased the currents of nvTRPM2 and hTRPM2. This suggests that these sites are essential for calcium-dependent channel gating. For the charge-neutralizing residues (glutamine and asparagine) in the calcium-binding site, our data showed that glutamine mutating to alanine or glutamate did not affect the channel activity, but glutamine mutating to lysine caused loss of function. Asparagine mutating to aspartate still remained functional, while asparagine mutating to alanine or lysine led to little channel activity. These results suggest that the side chain of glutamine has a less contribution to channel gating than does asparagine. However, our data indicated that both glutamine mutating to alanine or glutamate and asparagine mutating to aspartate accelerated the channel inactivation rate, suggesting that the calcium-binding site in the S2-S3 loop is important for calcium-dependent channel inactivation. Taken together, our results uncovered the effect of four key residues in the S2-S3 loop of TRPM2 on the TRPM2 gating process.

Clinical significance of serum level changes of heart-type fatty acid-binding protein and S-100B protein in elderly patients with chronic heart failure / 中华老年医学杂志

Objective@#To investigate serum level changes of heart-type fatty acid-binding protein(H-FABP)and S100 calcium-binding protein B(S-100B)protein in elderly patients with chronic heart failure and their clinical significance.@*Methods@#A total of 160 patients with chronic heart failure treated at our hospital were recruited, and 80 healthy individuals receiving regular check-ups were enrolled as normal controls.Serum levels of H-FABP and S-100B and cardiac function index scores were compared between patients with different cardiac function grades.Correlations of serum H-FABP and S-100B levels with N-terminal pro-B-type natrlure tiepeptide(NT-proBNP)and with cardiac function index scores in heart failure patients were analyzed.The sensitivity, specificity and accuracy of serum H-FABP, S-100B and NT-proBNP for heart failure detection were compared.@*Results@#Serum levels of H-FABP, S-100B and NT-proBNP in elderly patients with chronic heart failure were elevated with increased cardiac function grading(F=9.823, 11.573 and 13.056, P=0.013, 0.000 and 0.000), and serum levels of H-FABP, S-100B and NT-proBNP were higher in elderly patients with heart failure than in the control group(P<0.05). Serum levels of H-FABP and S-100B were positively correlated with serum NT-proBNP levels, cardiac function grading and left ventricular end-diastolic diameter(LVEDd)(r=0.527, 0.510 and 0.487, P=0.008, 0.003 and 0.002; r=0.604, 0.496 and 0.533, P=0.006, 0.005 and 0.003), and were negatively correlated with left ventricular ejection fraction(LVEF)(r=-0.536 and-0.528, P=0.005 and 0.008). The sensitivity, specificity and accuracy of serum H-FABP combined with S-100B for heart failure detection were 93.2%, 91.6% and 95.7%, respectively.@*Conclusions@#Serum levels of H-FABP and S-100B are high in elderly patients with heart failure, and they are correlated with serum NT-proBNP levels, cardiac function grading and LVEDd.H-FABP combined with S-100B has a high positive rate for heart failure detection.

Clinical significance of serum level changes of heart-type fatty acid-binding protein and S-100B protein in elderly patients with chronic heart failure / 中华老年医学杂志

Objective To investigate serum level changes of heart-type fatty acid-binding protein(H-FABP)and S100 calcium-binding protein B(S-100B)protein in elderly patients with chronic heart failure and their clinical significance.Methods A total of 160 patients with chronic heart failure treated at our hospital were recruited,and 80 healthy individuals receiving regular check-ups were enrolled as normal controls.Serum levels of H-FABP and S-100B and cardiac function index scores were compared between patients with different cardiac function grades.Correlations of serum H-FABP and S-100B levels with N-terminal pro-B-type natrlure tiepeptide(NT-proBNP)and with cardiac function index scores in heart failure patients were analyzed.The sensitivity,specificity and accuracy of serum H-FABP,S-100B and NT-proBNP for heart failure detection were compared.Results Serum levels of H-FABP,S-100B and NT-proBNP in elderly patients with chronic heart failure were elevated with increased cardiac function grading (F =9.823,11.573 and 13.056,P =0.013,0.000 and 0.000),and serum levels of H-FABP,S-100B and NT-proBNP were higher in elderly patients with heart failure than in the control group(P＜0.05).Serum levels of H-FABP and S-100B were positively correlated with serum NT-proBNP levels,cardiac function grading and left ventricular end-diastolic diameter(LVEDd) (r =0.527,0.510 and 0.487,P =0.008,0.003 and 0.002;r =0.604,0.496 and 0.533,P =0.006,0.005 and 0.003),and were negatively correlated with left ventricular ejection fraction(LVEF) (r =-0.536 and-0.528,P =0.005 and 0.008).The sensitivity,specificity and accuracy of serum H-FABP combined with S-100B for heart failure detection were 93.2％,91.6％ and 95.7％,respectively.Conclusions Serum levels of H-FABP and S-100B are high in elderly patients with heart failure,and they are correlated with serum NT-proBNP levels,cardiac function grading and LVEDd.H-FABP combined with S-100B has a high positive rate for heart failure detection.

The role and mechanism of S100 calcium binding protein B in osteoarthritis cartilage damage repair / 中国修复重建外科杂志

Objective: To investigate the role and mechanism of S100 calcium binding protein B (S100B) in osteoarthritis (OA) cartilage damage repair. Methods: Twenty New Zealand rabbits were randomly divided into control group and model group, with 10 rabbits in each group. Rabbits in the model group were injured by the right knee joint immobilization method to make the artilage injury model, while the control group did not deal with any injury. After 4 weeks, the levels of interleukin-1β (IL-1β) and tumor necrosis factor α (TNF-α) in synovial fluid were detected by ELISA method; the mRNA and protein expressions of S100B, fibroblast growth factor 2 (FGF-2), and FGF receptor 1 (FGFR1) in cartilage tissue were examined by real-time fluorescence quantitative PCR (qRT-PCR) and Western blot assay. Human synovial fibroblasts (SF) were isolated and cultured in vitro. The effects of S100B overexpression and knockdown on the levels of IL-1β and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. Moreover, the effects of FGFR1 knockdown in above S100 overexpression system on the levels of IL-1β and TNF-α (ELISA method) and the expressions of FGF-2 and FGFR1 gene (qRT-PCR) and protein (Western blot) were observed. Results: ELISA detection showed that the expressions of IL-1β and TNF-α in the synovial fluid of the model group were significantly higher than those of the control group ( P<0.05); qRT-PCR and Western blot detection showed that the mRNA and protein expressions of S100B, FGF-2, and FGFR1 in cartilage tissue were significantly higher than those of the control group ( P<0.05). Overexpression and knockdown S100 could respectively significantly increase and decrease lipopolysaccharides (LPS) induced IL-1β and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 ( P<0.05); whereas FGFR1 knockdown could significantly decrease LPS induced IL-1β and TNF-α levels elevation and the mRNA and protein expressions of FGF-2 and FGFR1 ( P<0.05). Conclusion: S100B protein can regulate the inflammatory response of SF and may affect the repair of cartilage damage in OA, and the mechanism may be related to the activation of FGF-2/FGFR1 signaling pathway.

S100A4 Gene is Crucial for Methionine-Choline-Deficient Diet-Induced Non-Alcoholic Fatty Liver Disease in Mice

PURPOSE: To explore the influence of S100 calcium binding protein A4 (S100A4) knockout (KO) on methionine-choline-deficient (MCD) diet-induced non-alcoholic fatty liver disease (NAFLD) in mice. MATERIALS AND METHODS: S100A4 KO mice (n=20) and their wild-type (WT) counterparts (n=20) were randomly divided into KO/MCD, Ko/methionine-choline-sufficient (MCS), WT/MCD, and WT/MCS groups. After 8 weeks of feeding, blood lipid and liver function-related indexes were measured. HE, Oil Red O, and Masson stainings were used to observe the changes of liver histopathology. Additionally, expressions of S100A4 and proinflammatory and profibrogenic cytokines were detected by qRT-PCR and Western blot, while hepatocyte apoptosis was revealed by TUNEL staining. RESULTS: Serum levels of aminotransferase, aspartate aminotransferase, triglyceride, and total cholesterol in mice were increased after 8-week MCD feeding, and hepatocytes performed varying balloon-like changes with increased inflammatory cell infiltration and collagen fibers; however, these effects were improved in mice of KO/MCD group. Meanwhile, total NAFLD activity scores and fibrosis were lower compared to WT+MCD group. Compared to WT/MCS group, S100A4 expression in liver tissue of WT/MCD group was enhanced. The expression of proinflammatory (TNF-α, IL-1β, IL-6) and profibrogenic cytokines (TGF-β1, COL1A1, α-SMA) in MCD-induced NAFLD mice were increased, as well as apoptotic index (AI). For MCD group, the expressions of proinflammatory and profibrogenic cytokines and AI in KO mice were lower than those of WT mice. CONCLUSION: S100A4 was detected to be upregulated in NAFLD, while S100A4 KO alleviated liver fibrosis and inflammation, in addition to inhibiting hepatocyte apoptosis.

Worsened brain edma and the level of serum HMGB1 and S100B of IL-4 knockout mice after traumatic brain injury / 中华行为医学与脑科学杂志

Objective To investigate the changes of brain edma and expression of blood high mobil-ity group box 1(HMGB1) and calcium binding protein S100B after traumatic brain injury (TBI) in IL-4 knockout (IL-4 KO) mice,and to explore the effects of IL-4 on traumatic brain injury. Methods Twenty male wild type ( WT) or twenty male IL-4 KO BALB/cJ mice were randomly divided into WT sham TBI group,WT TBI group,IL-4 KO sham TBI group and IL-4 KO TBI group(n=10 in each group).The model of traumatic brain injury was established by the free falling body epidural impact method,then the brain water content was measured. The expression of aquaporin-4 ( APQ4) and HMGB1 in injured brain of each group was detected by Western blot,and the concentration of HMGB1 and S100B in serum was detected by ELISA assay. Results ( 1 ) The brain water content of injured lateral brain of BALB/cJ mice with IL-4 gene knockout was significantly higher than that of wild type mice with brain injury model (WT group: (80.03± 0.35)％;IL-4 KO group:(81.93±0.41)％;P<0.05).(2) The Western blot showed that the expression of AQP4 and HMGB1 in brain tissue of BALB/cJ mice with IL-4 gene knockout was significantly higher than those in wild type mice after traumatic brain injury. ( 3) The results of ELISA showed that the levels of HMGB1 and S100B in the serum of IL-4 knockout BALB/cJ mice were significantly higher than those of wild type mice (HMGB1:WT group:(9.21±0.74)ng/ml;IL-4 gene knock-out group:(13.39±1.33)ng/ml,P<0.05;S100B protein:WT group:(11.11±0.84)pg/ml;IL-4 KO group: (18.11±2.02)pg/ml,P<0.05 ). Conclusion The brain tissue water content and the expression of APQ4 are increased in IL-4 KO TBI mice.The expression of HMGB1 in brain issue and serum and S100B in serum are also up-regulated.

Effects of ossotide injection on bone mineral density (BMD) , bone microstructure and biomechanical properties in ovariectomized rats / 中国比较医学杂志

Objective To observe the effect of ossotide injection on bone mineral density (BMD), bone microstructure and biomechanical properties and mRNA expression of small intestinal calcium binding protein (CaBp-D9K), and to study the mechanism of ossotide injection in the treatment of ovariectomized osteoporosis. Methods Forty-eight 3-month old SPF male rats with successful modeling (excision of bilateral ovaries) were randomly divided into the observation group and model group, 24 normal rats were divided into sham operation group (excised part of the mesenteric membrane), and 24 normal blank group. The blank group, sham operation group and model group were given normal saline, and the observation group was intragastrically given 1. 1 mg/kg ossotide. Two months after intervention, the bone volume (BV), trabecular bone volume (Tb. Th), trabecular number (Tb. N), trabecular separation (Tb. Sp), bone mineral density, bone biomechanics, serum 1,25(OH)2D3 levels and CaBp-D9K mRNA expression levels of small intestine were assessed and statistically analyzed. Results The bone mineral density, maximum load, fracture load, BV, Tb. Th, Tb. N, serum 1, 25 (OH ) 2D3 and intestinal CaBp-D9K mRNA expression level in the model group were significantly lower than those of the control group and sham operation group (P＜ 0. 05), Tb. Sp of the model group was significantly higher than that of the control group and sham operation group (P ＜ 0. 05 ). The bone mineral density, maximum load, fracture load, BV, Tb. Th, Tb. N, serum 1,25(OH)2D3 and intestinal CaBp-D9K mRNA expression level in the observation group were significantly higher than those of the model operation group, and the Tb. Sp of the observation group was lower than that of the model group (P ＜ 0. 05). Conclusions Ossotide injection treatment can reduce the degree of osteoporosis in ovariectomized rats, increasing intestinal CaBp-D9k mRNA expression and promoting intestinal calcium absorption may be its important mechanisms of action.

Diagnostic value of cranial ultrasonic examination combined with the detection of serum neuron spe-cific enolase,S100B and interleukin-6 on cerebral white matter lesions of premature infant / 新乡医学院学报

Objective To investigate the diagnostic value of cranial ultrasonic examination combined with the detection of serum neuron specific enolase(NSE),S100B and interleukin-6(IL-6)on cerebral white matter lesions of premature infant. Methods Thirty-nine premature infants with cerebral white matter injury diagnosed by cranial magnetic resonance imaging (MRI)in Women and Infants Hospital of Zhengzhou City from August 2016 to July 2017 were selected as observation group. Another thirty premature infants without brain white matter injury were selected as control group in the same period. On the 1st , 3rd and 7th day after birth,the serum NSE level was detected by the automatic time resolved fluoroimmunoassay system,the lev-els of serum S100B and IL-6 were detected by double anti sandwich enzyme-linked immunosorbent assay,and the changes of the cerebral white matter echoes around the cerebral ventricles were observed by cranial ultrasonic examination. The sensitivi-ty,specificity and accuracy combined detection of cranial ultrasonic examination combined with serum NSE,S100B and IL-6 in the diagnosis of white matter lesions in premature infants were analyzed. Results The detection rate of cerebral white matter lesions by cranial ultrasonic examination in the control group was 6. 45％(2 / 31),3. 23％(1 / 31)and 0. 00％(0 / 31)respec-tively;and it was 92. 31％(36 / 39),87. 18％(34 / 39)and 84. 62％(33 / 39)respectively on the 1st ,3rd and 7th day after birth in the observation group;the detection rate of cerebral white matter lesions in the observation group was significantly higher than that in the control group on the 1st ,3rd and 7th day after birth(χ2 = 51. 30,48. 69,49. 63;P < 0. 05). There was no signifi-cant difference in the grayscale value of cerebral white matter among the 1st ,3rd and 7th day after birth in the two groups(P >0. 05). The grayscale value of cerebral white matter in the observation group was significantly higher than that in the control group on the 1st ,3rd and 7th day after birth(P < 0. 05). There was no significant difference in serum S100B and IL-6 levels a-mong the 1st ,3rd and 7th day after birth in the control group(F = 0. 319,0. 307;P > 0. 05). There was the significant difference in serum NSE level among the 1st ,3rd and 7th day after birth in the control group(F = 3. 298,P < 0. 05),the serum NSE level on the 3rd and 7th day after birth was significantly lower than that on the 1st day after birth(P < 0. 05),the serum NSE level on the 7th day after birth was significantly lower than that on the 3rd day after birth(P < 0. 05). The levels of serum NSE,S100B and IL-6 in the observation group showed the downward trend on the 1st ,3rd and 7th day after birth(F = 3. 323,3. 517,3. 706;P < 0. 05). The levels of serum NSE,S100B and IL-6 on the 3rd and 7th day after birth were significantly lower than those on the 1st day after birth in the observation group(P < 0. 05). There was no significant difference in the levels of serum NSE, S100B and IL-6 between the 3rd and 7th day after birth in the observation group(P < 0. 05). The levels of serum NSE,S100B and IL-6 in the observation group were significantly higher than those in the control group on the 1st ,3rd and 7th day after birth (P < 0. 05). In the observation group,the grayscale value of cerebral white matter was positively correlated with the levels of serum NSE,S100B and IL-6 on the 1st day after birth(r = 3. 137,3. 358,3. 056;P < 0. 05);the grayscale value of cerebral white matter was positively correlated with the levels of serum NSE and S100B on the 3rd day after birth(r = 2. 872,2. 347;P <0. 05);the grayscale value of cerebral white matter was positively correlated with serum S100B level on the 7th day after birth (r = 2. 791,P < 0. 05). The sensitivity,specificity and accuracy of combined detection of cranial ultrasonic examination and, serum NSE and S100B in the diagnosis of cerebral white matter lesions in premature infants was 100. 00％,93. 54％ and 97. 14％ respectively. Conclusion The combined detection of cranial ultrasonic examination,serum NSE and S100B can sig-nificantly improve the accuracy of early diagnosis of cerebral white matter lesions.

The expression and significance of S100A8 in Oral Squamous Cell Carcinoma / 实用口腔医学杂志

The expression of calcium binding protein S100A8 in 30 controls of normal oral tissue and 35 cases of OSCC was detected by immunohistochemical staining and Western blot respectively. The positive expression of S100A8 protein in OSCC and the controls was 68. 5％ and 36. 7％ respectively(P ＜ 0. 05). S100A8 may play a role in the development of OSCC.

Serum S100B as a brain injury marker after intracerebral hemorrhage / 国际脑血管病杂志

Cerebrospinal fluid and level of blood S100B protein are significantly higher in patients with intracerebral hemorrhage,which are associated the differentiation of stroke,damage of blood-brain barrier,hematoma volume,brain edema,degree of nerve function defect,and outcomes.Therefore,S100B is expected to be used in the diagnosis of intracerebral hemorrhage,assessment of injury and outcomes,and even as a biomarker of therapeutic targets.

Progresses of HRC gene in hepatocellular carcinoma in chidren / 国际儿科学杂志

The histidine enriched calcium protein (HRC)is a new type of sarcoplasmic reticulum (SR) regulator of Ca2 + absorption,storage and release,located in the lumen cavity,with a combination of high capacity and low affinity of calcium ions.Recent studies have shown that abnormal expression of HRC plays a key role in the development of hepatocellular carcinoma.This article reviews the role of HRC in hepatocellular carcinoma.