Disrupted ageing in place: Urbanisation and displaced older villagers in Suzhou, China.

OBJECTIVE: This study examines the impacts of urbanisation-induced displacement on rural older villagers and the issues of rebuilding ageing in place in Suzhou Municipality in China's Jiangsu Province. METHODS: The study employed a qualitative research method involving three measures of data collection, including 20 older-adult interviews, 14 key informant interviews (with street and community administrators, managers of service companies, managers of nursing homes and community doctor) and participant observation of older villagers' daily life in urban resettlement communities. RESULTS: The displacement and resettlement of villagers for urbanisation had serious negative impacts on older villagers, including financial insecurity, relative deprivation and radical changes to the living environment. The community services were limited and insufficient, but the resettlement of the whole village in the same place enabled the village community to maintain social and cultural continuities, which facilitated older villagers' adaptation to the new urban place. Filial piety, though weakened and transformed, continued to play an important role in regulating old-age support, but descending familism reduced family resources for old-age support. CONCLUSIONS: This study highlights the importance of examining the impacts of external social and economic forces, such urbanisation in China, on ageing in place. We draw three conclusions based on empirical research in Suzhou: (1) the resettlement of older villagers in urban areas did not significantly narrow the rural-urban gap in old-age support in Suzhou; (2) urbanisation-induced displacement in China affected older residents differently from gentrification in Western countries, due to different processes of compensation and resettlement as well as China's rural-urban welfare gap; and (3) community services for displaced older villagers are limited, but social and cultural continuities before and after resettlement have helped older villagers adapt to the new urban place.

Asporin Interacts With HER2 to Promote Thyroid Cancer Metastasis via the MAPK/EMT Signaling Pathway.

Approximately 85% of histological subtypes of thyroid cancer are papillary thyroid cancer (PTC), and the morbidity and mortality of PTC patients rapidly increased due to lymph node metastases or distant metastasis. Therefore, it needs to distill an enhanced understanding of the pathogenesis of PTC patients with lymph node metastases or distant metastasis. We employed the TMT-based quantitative proteomics approach to identify and analyze differentially expressed proteins in PTC with different degrees of lymph node metastases. Compared with paired normal tissues, asporin is overexpressed in PTC-N0, PTC-N1a, and PTC-N1b tumorous tissues via proteomics, western blotting, and immunohistochemistry assays. Functionally, asporin is mainly expressed in the extracellular matrix, cell membrane, and cytoplasm of PTC tumorous tissues, and promotes thyroid cancer cell proliferation, migration, and invasion. Mechanistically, asporin, interacting with HER2, co-localizes HER2 on the cell membrane and cytoplasm, and the asporin/HER2/SRC/EGFR axis upregulate the expression of EMT-activating transcription factors through the MAPK signaling pathway. Clinically, asporin can be regarded as a serological biomarker to identify PTC patients with or without lymph node metastasis, and high expression of asporin in PTC tumorous tissues is a risk factor for poor prognosis.

[Sensitization Spectrum of 16 362 Patients with Allergic Diseases in Peking University Third Hospital].

Objective To retrospectively analyze the sensitization spectrum of 16 362 patients with allergic diseases treated in the Peking University Third Hospital and provide reference for the prevention and treatment of allergic diseases.Methods A total of 16 362 patients with allergic diseases treated in the Peking University Third Hospital from January 2009 to September 2021 were selected.The serum levels of total IgE and antigen-specific IgE(sIgE)were determined.Furthermore,the selected patients were classified into different groups according to gender,age,and disease occurrence month.Results The mean level of total IgE in 7919 patients was 92.4(34.8, 241.0)kU/L.The sIgE levels of 34 allergens in 5495 patients were determined via the ImmunoCAP system,with a positive sIgE rate of 54.23%.The top 5 allergens with high positive rates were mountain juniper pollen(43.78%),cat dander(38.76%),egg white(33.38%),Japanese hop(32.03%),and mugwort(31.82%).The sIgE levels of 20 allergens in 10 867 patients were determined via the EURO system,with a positive sIgE rate of 35.79%.The top 5 allergens with high positive rates were mugwort(15.86%),house dust mite mix(10.17%),cat dander(8.32%),house dust(4.71%),and tree pollen mix(4.04%).The analysis based on gender showed that the allergen positive rates in males were higher than those in females.The positive rates of egg white and cow's milk gradually decreased with the increase in age,while those of the inhaled allergens gradually increased during 10-19 years and then gradually decreased.The analysis based on disease occurrence month showed that the population with allergic diseases in Beijing surged in summer and autumn due to the inhaled allergens including mugwort,tree pollen mix,common ragweed,cocklebur,goosefoots,Japanese hop,timothy grass,and weed mix.Conclusions Among the 16 362 patients with allergic diseases treated in the Peking University Third Hospital,male patients showed higher sensitivity to allergens.The positive rates of egg white and cow's milk gradually decreased with the increase in age,while those of inhaled allergens were highest in patients of 10-19 years.The population of allergic diseases in Beijing surged in summer and autumn due to the inhaled allergens.

External Quality Assessment for Molecular Detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) in Clinical Laboratories.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) poses a huge threat to public health. Viral nucleic acid testing is the diagnostic gold standard and can play an important role in the prevention and control of this infection. In this study, bacteriophage MS2 virus-like particles encapsulating specific RNA sequences of SARS-CoV-2 and other coronaviruses were prepared by genetic engineering. The assessment panel, consisting of four positive samples with concentrations of 2.8, 3.5, 4.2, and 4.9 log10 copies/mL and five negative samples with other human coronaviruses, was prepared and distributed to evaluate the accuracy of routine viral RNA detection. Results of 931 panels from 844 laboratories were collected. The overall percentage agreement, positive percentage agreement (PPA), and negative percentage agreement, defined as the percentage of agreement between the correct results and total results submitted for all, positive, and negative samples were 96.8% (8109/8379), 93.9% (3497/3724), and 99.1% (4612/4655), respectively. For samples with concentrations of 4.9 and 4.2 log10 copies/mL, the PPAs were >95%. However, for 3.5 and 2.8 log10 copies/mL, the PPAs were 94.6% (881/931) and 84.9% (790/931), respectively. For all negative samples, the negative percentage agreement values were >95%. Thus, most laboratories can reliably detect SARS-CoV-2. However, further improvement and optimization are required to ensure the accuracy of detection in panel members with lower concentrations of viral RNA.

Multifaceted Roles of Asporin in Cancer: Current Understanding.

The small leucine-rich proteoglycan (SLRP) family consists of 18 members categorized into five distinct classes, the traditional classes I-III, and the non-canonical classes IV-V. Unlike the other class I SLRPs (decorin and biglycan), asporin contains a unique and conserved stretch of aspartate (D) residues in its N terminus, and germline polymorphisms in the D-repeat-length are associated with osteoarthritis and prostate cancer progression. Since the first discovery of asporin in 2001, previous studies have focused mainly on its roles in bone and joint diseases, including osteoarthritis, intervertebral disc degeneration and periodontal ligament mineralization. Recently, asporin gene expression was also reported to be dysregulated in tumor tissues of different types of cancer, and to act as oncogene in pancreatic, colorectal, gastric, and prostate cancers, and some types of breast cancer, though it is also reported to function as a tumor suppressor gene in triple-negative breast cancer. Furthermore, asporin is also positively or negatively correlated with tumor proliferation, migration, invasion, and patient prognosis through its regulation of different signaling pathways, including the TGF-ß, EGFR, and CD44 pathways. In this review, we seek to elucidate the signaling pathways and functions regulated by asporin in different types of cancer and to highlight some important issues that require investigation in future research.

In-Depth Proteomics Analysis to Identify Biomarkers of Papillary Thyroid Cancer Patients Older Than 45 Years with Different Degrees of Lymph Node Metastases.

PURPOSE: Investigations of the molecular mechanisms underlying the metastatic phenotype of papillary thyroid cancer (PTC) and identification of novel candidate biomarkers to better predict PTC metastasis are urgently required. EXPERIMENTAL DESIGN: Tandem mass tag-based quantitative proteomics approach is used to identify differentially expressed proteins (DEPs) in PTC tumorous tissues with different degrees of lymph node metastases (LNMs). Furthermore, DEPs and their clinical significance are analyzed in another independent Cancer Genome Atlas dataset. RESULTS: The protein profiles among tumorous tissues with different degrees of LNMs are clearly distinguished, while the protein profiles in normal tissues are remarkably similar. DEPs in tumorous tissues are mostly enriched in the categories associated with pathological hallmarks of cancer, including extracellular matrix, metabolism, and cell growth. The expression patterns of six DEPs (LAMC2, LAMB3, ATP5A1, MYO1G, S100A4, and FAS) are confirmed by the Cancer Genome Atlas dataset. Additionally, the elevated expression of LAMC2 and MYO1G mRNA levels in tumorous tissues show a positive relationship with unfavorable variables, including larger tumor size, LNMs, high AJCC staging, BRAFV600E mutation, and poor prognosis. CONCLUSIONS AND CLINICAL RELEVANCE: LAMC2 and MYO1G are identified as potential candidate biomarkers for the prediction of PTC metastasis and prognosis.

Clinicopathological predictors of occult lateral neck lymph node metastasis in papillary thyroid cancer: A meta-analysis.

BACKGROUND: This meta-analysis aimed to identify the clinicopathological factors that could predict the risk of occult lateral neck lymph node metastasis (OLLNM) in N0/N1a papillary thyroid cancer (PTC). METHODS: A literature search of PubMed, Web of Science, OvidSP, and Chinese National Knowledge Infrastructure databases was performed using relevant keywords. Specific odds ratios and confidence intervals were calculated. RESULTS: The final analysis included 15 studies with a total of 5342 patients. OLLNM was found to be significantly associated with some clinicopathological features, including age <45 years, male sex, extrathyroidal extension, tumor location in the upper pole, tumor size >10 mm, positive central lymph node metastasis, number of central lymph node metastasis ≥3, and vascular invasion. CONCLUSIONS: Fine-needle aspiration (FNA) cytology or FNA-Tg test might be an appropriate and reasonable intervention in the patients with N0/N1a PTC with an increased risk of OLLNM.

The interactome and proteomic responses of ALKBH7 in cell lines by in-depth proteomics analysis.

BACKGROUND: ALKBH7 is a mitochondrial protein, involved in programmed necrosis, fatty acid metabolism, cell cycle regulation, and prostate cancer disease. However, the exact roles of ALKBH7 and the underlying molecular mechanisms remain mysterious. Thus, investigations of the interactome and proteomic responses of ALKBH7 in cell lines using proteomics strategies are urgently required. METHODS: In the present study, we investigated the interactome of ALKBH7 in mitochondria through immunoprecipitation-mass spectrometry/mass spectrometry (IP-MS/MS). Additionally, we established the ALKBH7 knockdown and overexpression cell lines and further identified the differentially expressed proteins (DEPs) in these cell lines by TMT-based MS/MS. Two DEPs (UQCRH and HMGN1) were validated by western blotting analysis. RESULTS: Through bioinformatic analysis the proteomics data, we found that ALKBH7 was involved in protein homeostasis and cellular immunity, as well as cell proliferation, lipid metabolism, and programmed necrosis by regulating the expression of PTMA, PTMS, UQCRH, HMGN1, and HMGN2. Knockdown of ALKBH7 resulted in upregulation of UQCRH and HMGN1 expression, and the opposite pattern of expression was detected in ALKBH7 overexpression cell lines; these results were consistent with our proteomics data. CONCLUSION: Our findings indicate that the expression of UQCRH and HMGN1 is regulated by ALKBH7, which provides potential directions for future studies of ALKBH7. Furthermore, our results also provide comprehensive insights into the molecular mechanisms and pathways associated with ALKBH7.

Proteomics study of serum exosomes from papillary thyroid cancer patients.

Lymph node metastasis (LNM) in papillary thyroid cancer (PTC) is related to increased risk of recurrence and poor prognosis. Tumour exosomes have been shown to be associated with metastasis of cancer cells. Therefore, we aim to identify the characteristics and biological functions of serum exosomes in lymph node metastases of PTC. We compared proteome profiles of serum-purified exosomes (SPEs) from PTC patients with LNM, PTC patients without LNM, and healthy donors, using a combination of liquid chromatography-tandem mass spectroscopy analyses and tandem mass tag label quantitation analysis. We identified 1569 proteins by two or more unique peptides. Compared with the SPEs of PTC patients without LNM, we found 697 differentially expressed proteins in the SPEs of PTC patients with LNM. Our results revealed overexpression of specific proteins with well-established links to cancer cell metastasis, such as SRC, TLN1, ITGB2 and CAPNS1. Consistent with mass spectrum results, we performed Western blot to detect the expression of these proteins in individual sample. Biological pathway analyses showed that integrin signalling was aberrantly activated in the SPEs of PTC patients with LNM compared to those without LNM. Our study reveals that SPEs of PTC patients with lymph node metastases promote BHT101 thyroid cancer cell invasiveness, but have no apparent influence on cell migration. In the serum exosomes of PTC patients with LNM, integrin-associated proteins are obviously upregulated. These proteomic findings will contribute to elucidation of the pathophysiological functions of tumour-derived exosomes.

Quantitative Proteomics Analysis of Sporadic Medullary Thyroid Cancer Reveals FN1 as a Potential Novel Candidate Prognostic Biomarker.

BACKGROUND: Sporadic medullary thyroid cancer (MTC) is a rare neuroendocrine tumor. Currently, although the diagnosis of sporadic MTC is relatively simple, the need to discover novel candidate prognostic biomarkers for sporadic MTC and investigate the underlying mechanism involved in this rare disease is urgent. MATERIALS AND METHODS: We employed tandem mass tag-based liquid chromatography-mass spectrometry to identify and analyze differentially expressed proteins (DEPs) in sporadic MTC. Western blotting was used to validate the DEPs. Immunohistochemistry was performed to investigate FN1 and RPS6KA3 in an independent set of sporadic MTC tissues. Immunohistochemical data were analyzed by different statistical methods. RESULTS: Three hundred eighty-eight DEPs were identified in mass spectrometry, mainly involved in the extracellular matrix, cytoskeletal remodeling, or oxidoreductase activity. Among them, THBS1, MMP9, FN1, RPS6KA3, SYT1, and carcinoembryonic antigen were successfully validated by Western blot. In addition, FN1 and RPS6KA3, enriched in extracellular matrix (ECM) remodeling and the mitogen-activated protein kinase (MAPK) signaling pathway, respectively, were investigated in an independent set of sporadic MTC tissues. Receiver-operator characteristic curve analysis showed that FN1 and RPS6KA3 can be used for discriminating sporadic MTC tumorous tissues from paired normal thyroid tissues, and the clinical biomarker calcitonin was positively correlated with FN1 and RPS6KA3 in tumorous tissues. Furthermore, the immunohistochemical scores of FN1 in tumorous tissue showed an inverse relationship with tumor classification, lymph node classification, and American Joint Committee on Cancer stage. Through univariate and multivariate analysis for progression-free survival, we also found that low FN1 expression in tumorous tissues was an independent worse prognostic factor for progression-free survival. CONCLUSION: We identified that the pathophysiology of sporadic MTC involve numerous pathways, including the synaptic vesicle pathway, the MAPK signaling pathway, and the ECM remodeling pathway. Furthermore, our study also identified FN1 as novel prognostic biomarkers related to the pathophysiologic changes in sporadic MTC. IMPLICATIONS FOR PRACTICE: Proteomic dissection and prognostic biomarkers are scarce in sporadic medullary thyroid cancer (MTC). This article reports the use of proteomics technology to comprehensively investigate the molecular mechanisms of sporadic MTC, which resulted in the identification of FN1 as a novel candidate prognostic biomarker.

Multiple roles of Ring 1 and YY1 binding protein in physiology and disease.

Ring 1 and YY1 binding protein (RYBP) was first identified in 1999, and its structure includes a conserved Npl4 Zinc finger motif at the N-terminus, a central region that is characteristically enriched with arginine and lysine residues and a C-terminal region enriched with serine and threonine amino acids. Over nearly 20 years, multiple studies have found that RYBP functions as an organ developmental adaptor. There is also evidence that RYBP regulates the expression of different genes involved in various aspects of biological processes, via a mechanism that is dependent on interactions with components of PcG complexes and/or through binding to different transcriptional factors. In addition, RYBP interacts directly or indirectly with apoptosis-associated proteins to mediate anti-apoptotic or pro-apoptotic activity in both the cytoplasm and nucleus of various cell types. Furthermore, RYBP has also been shown to act as tumour suppressor gene in different solid tumours, but as an oncogene in lymphoma and melanoma. In this review, we summarize our current understanding of the functions of this multifaceted RYBP in physiological and pathological conditions, including embryonic development, apoptosis and cancer, as well as its role as a component of polycomb repressive complex 1.

Proteomic Profiling of Brain and Testis Reveals the Diverse Changes in Ribosomal Proteins in fmr1 Knockout Mice.

Fragile X syndrome (FXS), the leading cause of inherited forms of mental retardation and autism, is caused by the transcriptional silencing of fmr1 encoding the fragile X mental retardation protein (FMRP). FMRP is an RNA-binding protein that is a widely expressed, but primarily in the brain and testis, and associated approximately 4% of transcripts. Macro-orchidism is a common symptom associated with FXS both in humans and mice. Thus, we analyze the pooled samples of cerebral cortex, hippocampus and testis from both the fmr1-KO and wild-type mice by a LC-MS/MS proteomic study. Among the identified proteins, most of those showing significant changes in expression were up- or downregulated in the absence of FMRP. Proteins (FMRP, RPS8, RPL23a and ATPIF1, RPL6, GAP43, MTCH2 and MPZ in brain, and FMRP, CAH3, AKR1B7 and C9 in testis) identified by MS/MS were also verified by Western blotting. The Gene Ontology and WikiPathways analysis revealed that the differentially expressed proteins were clustered in the polyribosome and RNA-binding protein categories in both cerebral cortex and hippocampus, but not in testis. Although this study was limited by the little number of samples, our results provide detailed insights into the ribosomal protein profiles of cerebral cortex, hippocampus and testis in the absence of FMRP. Our studies also provide a better understanding of protein profile changes and the underlying dysregulated pathways arising from fmr1 silencing in FXS.

Multiple functions of the E3 ubiquitin ligase CHIP in immunity.

The carboxyl terminal of Hsp70-interacting protein (CHIP) is an E3 ubiquitin ligase that plays a pivotal role in the protein quality control system by shifting the balance of the folding-refolding machinery toward the degradative pathway. However, the precise mechanisms by which nonnative proteins are selected for degradation by CHIP either directly or indirectly via chaperone Hsp70 or Hsp90 are still not clear. In this review, we aim to provide a comprehensive model of the mechanism by which CHIP degrades its substrate in a chaperone-dependent or direct manner. In addition, through tight regulation of the protein level of its substrates, CHIP plays important roles in many physiological and pathological conditions, including cancers, neurological disorders, cardiac diseases, bone metabolism, immunity, and so on. Nonetheless, the precise mechanisms underlying the regulation of the immune system by CHIP are still poorly understood despite accumulating developments in our understanding of the regulatory roles of CHIP in both innate and adaptive immune responses. In this review, we also aim to provide a view of CHIP-mediated regulation of immune responses and the signaling pathways involved in the model described. Finally, we discuss the roles of CHIP in immune-related diseases.

Quantitative proteomic profiling for clarification of the crucial roles of lysosomes in microbial infections.

Lysosomes play vital roles in both innate and adaptive immunity. It is widely accepted that lysosomes do not function exclusively as a digestive organelle. It is also involved in the process of immune cells against pathogens. However, the changes in the lysosomal proteome caused by infection with various microbes are still largely unknown, and our understanding of the proteome of the purified lysosome is another obstacle that needs to be resolved. Here, we performed a proteomic study on lysosomes enriched from THP1 cells after infection with Listeria monocytogenes (L.m), Herpes Simplex Virus 1 (HSV-1) and Vesicular Stomatitis Virus (VSV). In combination with the gene ontology (GO) analysis, we identified 284 lysosomal-related proteins from a total of 4560 proteins. We also constructed the protein-protein interaction networks for the differentially expressed proteins and revealed the core lysosomal proteins, including SRC in the L. m treated group, SRC, GLB1, HEXA and HEXB in the HSV-1 treated group and GLB1, CTSA, CTSB, HEXA and HEXB in the VSV treated group, which are involved in responding to diverse microbial infections. This study not only reveals variable lysosome responses depending on the bacterial or virus infection, but also provides the evidence based on which we propose a novel approach to proteome research for investigation of the function of the enriched organelles.

Comprehensive proteome analysis of lysosomes reveals the diverse function of macrophages in immune responses.

Phagocytosis and autophagy in macrophages have been shown to be essential to both innate and adaptive immunity. Lysosomes are the main catabolic subcellular organelles responsible for degradation and recycling of both extracellular and intracellular material, which are the final steps in phagocytosis and autophagy. However, the molecular mechanisms underlying lysosomal functions after infection remain obscure. In this study, we conducted a quantitative proteomics analysis of the changes in constitution and glycosylation of proteins in lysosomes derived from murine RAW 264.7 macrophage cells treated with different types of pathogens comprising examples of bacteria (Listeria monocytogenes, L. m), DNA viruses (herpes simplex virus type-1, HSV-1) and RNA viruses (vesicular stomatitis virus, VSV). In total, 3,704 lysosome-related proteins and 300 potential glycosylation sites on 193 proteins were identified. Comparative analysis showed that the aforementioned pathogens induced distinct alterations in the proteome of the lysosome, which is closely associated with the immune functions of macrophages, such as toll-like receptor activation, inflammation and antigen-presentation. The most significant changes in proteins and fluctuations in glycosylation were also determined. Furthermore, Western blot analysis showed that the changes in expression of these proteins were undetectable at the whole cell level. Thus, our study provides unique insights into the function of lysosomes in macrophage activation and immune responses.

Protein content and functional characteristics of serum-purified exosomes from patients with colorectal cancer revealed by quantitative proteomics.

Tumor cells of colorectal cancer (CRC) release exosomes into the circulation. These exosomes can mediate communication between cells and affect various tumor-related processes in their target cells. We present a quantitative proteomics analysis of the exosomes purified from serum of patients with CRC and normal volunteers; data are available via ProteomeXchange with identifier PXD003875. We identified 918 proteins with an overlap of 725 Gene IDs in the Exocarta proteins list. Compared with the serum-purified exosomes (SPEs) of normal volunteers, we found 36 proteins upregulated and 22 proteins downregulated in the SPEs of CRC patients. Bioinformatics analysis revealed that upregulated proteins are involved in processes that modulate the pretumorigenic microenvironment for metastasis. In contrast, differentially expressed proteins (DEPs) that play critical roles in tumor growth and cell survival were principally downregulated. Our study demonstrates that SPEs of CRC patients play a pivotal role in promoting the tumor invasiveness, but have minimal influence on putative alterations in tumor survival or proliferation. According to bioinformatics analysis, we speculate that the protein contents of exosomes might be associated with whether they are involved in premetastatic niche establishment or growth and survival of metastatic tumor cells. This information will be helpful in elucidating the pathophysiological functions of tumor-derived exosomes, and aid in the development of CRC diagnostics and therapeutics.

Investigation of proteome changes in osteoclastogenesis in low serum culture system using quantitative proteomics.

BACKGROUND: RAW 264.7 cells can differentiate into osteoclasts when cultured in medium supplemented with 1 % FBS. However, the proteomic changes in the development of RAW 264.7 cells into osteoclasts in low serum culture system have not been elucidated. Therefore, we conducted quantitative proteomics analysis to investigate proteomic changes during osteoclastogenesis in low serum culture system. RESULTS: Our study confirmed that mature multinucleated osteoclasts were generated in a low serum culture system, validated by upregulated expression of 15 characteristic marker proteins, including TRAP, CTSK, MMP9, V-ATPase and ITGAV. Proteomics results demonstrated that 549 proteins expressed differentially in osteoclastogenesis in low serum culture system. In-depth bioinformatics analysis suggested that the differentially expressed proteins were mainly involved in mitochondrial activities and energy metabolism, including the electron transport chain pathway, TCA cycle pathway, mitochondrial LC-fatty acid beta-oxidation pathway and fatty acid biosynthesis pathway. The data have been deposited to the ProteomeXchange with identifier PXD001935. CONCLUSION: Osteoclast formation is an ATP consuming procedure, whether occurring in a low serum culture system or a conventional culture system. In contrast to osteoclasts formed in conventional culture system, the fatty acid biosynthesis pathway was upregulated in osteoclasts cultured in low serum condition.

Protein profile changes in the frontotemporal lobes in human severe traumatic brain injury.

Severe traumatic brain injury (sTBI) is a serious public health issue with high morbidity and mortality rates. Previous proteomic studies on sTBI have mainly focused on human cerebrospinal fluid and serum, as well as on brain protein changes in murine models. However, human proteomic data in sTBI brain is still scarce. We used proteomic and bioinformatic strategies to investigate variations in protein expression levels in human brains after sTBI, using samples from the Department of Neurosurgery, Affiliated Hospital of Hebei University (Hebei, China). Our proteomic data identified 4031 proteins, of which 160 proteins were overexpressed and 5 proteins were downregulated. Bioinformatics analysis showed significant changes in biological pathways including glial cell differentiation, complement activation and apolipoprotein catalysis in the statin pathway. Western blot verification of protein changes in a subset of the available tissue samples showed results that were consistent with the proteomic data. This study is one of the first to investigate the whole proteome of human sTBI brains, and provide a characteristic signature and overall landscape of the sTBI brain proteome.

Quantitative protein profiling of hippocampus during human aging.

The hippocampus appears commonly affected by aging and various neurologic disorders in humans, whereas little is known about age-related change in overall protein expression in this brain structure. Using the 4-plex tandem mass tag labeling, we carried out a quantitative proteomic study of the hippocampus during normal aging using postmortem brains from Chinese subjects. Hippocampal samples from 16 subjects died of non-neurological/psychiatric diseases were divided into 4 age groups: 22-49, 50-69, 70-89, and >90. Among 4582 proteins analyzed, 35 proteins were significantly elevated, whereas 25 proteins were downregulated, along with increasing age. Several upregulated proteins, including transgelin, vimentin, myosin regulatory light polypeptide 9, and calcyphosin, were further verified by quantitative Western blot analysis of hippocampal tissues from additional normal subjects. Bioinformatic analysis showed that the upregulated and downregulated proteins were largely involved in several important protein-protein interaction networks. Proteins in the electron transport chain and synaptic vesicle fusion pathway were consistently downregulated with aging, whereas proteins associated with Alzheimer's disease showed little change. Our study demonstrates substantial protein profile changes in the human hippocampus during aging, which could be of relevance to age-related loss of hippocampal functions.