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1.
Mol Neurobiol ; 2024 Jun 14.
Article in English | MEDLINE | ID: mdl-38877366

ABSTRACT

Intracerebral hemorrhage (ICH) is a common cerebrovascular disease that can lead to severe neurological dysfunction in surviving patients, resulting in a heavy burden on patients and their families. When ICH occurs, the blood‒brain barrier is disrupted, thereby promoting immune cell migration into damaged brain tissue. As important immunosuppressive T cells, regulatory T (Treg) cells are involved in the maintenance of immune homeostasis and the suppression of immune responses after ICH. Treg cells mitigate brain tissue damage after ICH in a variety of ways, such as inhibiting the neuroinflammatory response, protecting against blood‒brain barrier damage, reducing oxidative stress damage and promoting nerve repair. In this review, we discuss the changes in Treg cells in ICH clinical patients and experimental animals, the mechanisms by which Treg cells regulate ICH and treatments targeting Treg cells in ICH, aiming to support new therapeutic strategies for clinical treatment.

2.
Adv Sci (Weinh) ; 11(24): e2308384, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38634607

ABSTRACT

Cell-specific transcriptional regulatory networks (TRNs) play vital roles in plant development and response to environmental stresses. However, traditional single-cell mono-omics techniques are unable to directly capture the relationships and dynamics between different layers of molecular information within the same cells. While advanced algorithm facilitates merging scRNA-seq and scATAC-seq datasets, accurate data integration remains a challenge, particularly when investigating cell-type-specific TRNs. By examining gene expression and chromatin accessibility simultaneously in 16,670 Arabidopsis root tip nuclei, the TRNs are reconstructed that govern root tip development under osmotic stress. In contrast to commonly used computational integration at cell-type level, 12,968 peak-to-gene linkage is captured at the bona fide single-cell level and construct TRNs at an unprecedented resolution. Furthermore, the unprecedented datasets allow to more accurately reconstruct the coordinated changes of gene expression and chromatin states during cellular state transition. During root tip development, chromatin accessibility of initial cells precedes gene expression, suggesting that changes in chromatin accessibility may prime cells for subsequent differentiation steps. Pseudo-time trajectory analysis reveal that osmotic stress can shift the functional differentiation of trichoblast. Candidate stress-related gene-linked cis-regulatory elements (gl-cCREs) as well as potential target genes are also identified, and uncovered large cellular heterogeneity under osmotic stress.


Subject(s)
Arabidopsis , Osmotic Pressure , Arabidopsis/genetics , Arabidopsis/metabolism , Arabidopsis/growth & development , Gene Expression Regulation, Plant/genetics , Single-Cell Analysis/methods , Gene Regulatory Networks/genetics , Plant Roots/genetics , Plant Roots/growth & development , Meristem/genetics , Meristem/metabolism
4.
Heliyon ; 10(3): e24802, 2024 Feb 15.
Article in English | MEDLINE | ID: mdl-38318059

ABSTRACT

Background: Our objective was to assess the viability and oncological security of a gasless, transaxillary single-incision endoscopic procedure for performing total thyroidectomy and bilateral central neck dissection (TT + BCND). This study focused on patients diagnosed with bilateral papillary thyroid microcarcinoma (PTMC). Method: Between April 2020 and November 2021, 22 patients with bilateral PTMC underwent single-incision, gasless, transaxillary endoscopic TT + BCND. The patients' clinicopathologic characteristics, surgical completeness and complications were analyzed. Result: Single-incision, gasless, transaxillary endoscopic TT + BCND was successful performed in all patients. The median (IQR) total surgical time was 143 (85-160) min. Only two patients experienced transient unilateral RLN palsy or transient hypocalcemia. All these complications resolved within 1 month after surgery. The median duration of hospital stay after surgery was 4 (3-4.5) days. The median hospitalization expense for these patients was 3848 (3781-4145) USD. The median number of lymph node yielded was 10.5 (8-15). The cosmetic outcomes were well-received by all individuals. Conclusion: In certain cases, gasless, transaxillary endoscopic TT + BCND procedure performed through a single incision proved to be a secure alternative for managing bilateral PTMC.

5.
Aging Cell ; 23(3): e14055, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38044578

ABSTRACT

The heterogeneity of aging has been investigated at cellular and organic levels in the mouse model and human, but the exploration of aging heterogeneity at whole-organism level is lacking. C. elegans is an ideal model organism for studying this question as they are self-fertilized and cultured in the same chamber. Despite the tremendous progress made in single-cell proteomic analysis, there is few single-worm proteomics studies about aging. Here, we apply single-worm quantitative mass spectrometry to quantify the heterogenous proteomic changes during aging across individuals, a total of 3524 proteins from 157 C. eleagns individuals were quantified. A reconstructed C. elegans aging trajectory and proteomic landscape of fast-aging individuals were used to analyze the heterogeneity of C. elegans aging. We characterized inter-individual proteomic variation during aging and revealed contributing factors that distinguish fast-aging individuals from their siblings.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Mice , Humans , Caenorhabditis elegans/genetics , Caenorhabditis elegans/metabolism , Caenorhabditis elegans Proteins/genetics , Caenorhabditis elegans Proteins/metabolism , Proteomics/methods , Aging , Disease Models, Animal
6.
Surg Endosc ; 37(12): 9255-9262, 2023 12.
Article in English | MEDLINE | ID: mdl-37875693

ABSTRACT

BACKGROUND: In a previous study, we proposed a novel anatomy-based five-settlement method for transaxillary endoscopic thyroidectomy (fs-TAT) for patients with papillary thyroid carcinoma. The safety of this new method has been reported in a retrospective study of a single cohort. The safety and short-term oncological outcome of this method was confirmed by comparing it with conventional open surgery (COT) in patients with papillary thyroid microcarcinoma. METHODS: The medical records of patients who underwent fs-TAT or COT by a single surgeon from February 2019 to December 2021 were reviewed retrospectively. All patients were diagnosed with papillary thyroid microcarcinoma and underwent lobectomy and ipsilateral central compartment neck dissection. Propensity score matching was used to compare the technical safety and short-term oncologic outcomes of fs-TAT and COT for the purpose of reducing potential selection bias. Reporting was consistent with the STROCSS 2021 guidelines. RESULT: After propensity score matching, 460 (fs-TAT: 230; COT: 230) patients remained in the study population. There were no significant differences in sex, age, tumor size, Hashimoto's thyroiditis, or tumor multifocality between the groups. The operative time was longer [104.5 (90.3, 120.0) vs. 62.0 (52.0, 76.0), P < 0.001] and the total postoperative drainage volume [135(90, 210) vs. 75 (55, 115), P < 0.001] was greater in the fs-TAT group than in the COT group. However, intraoperative bleeding [3.0 (2.0, 5.0) vs. 5.0 (5.0, 7.5), P < 0.001] was greater, and the median number of lymph nodes yielded [5.0 (2.3, 8.0) vs. 7.0 (5.0, 11.0), P < 0.001] was greater in the COT group than in the fs-TAT group. The groups exhibited no significant difference in the rate of complications (fs-TAT: 2.2% vs. COT: 2.6%, P = 0.856), rate of positive lymph nodes (fs-TAT: 32.2% vs. COT: 36.5%, P = 0.377), length of postoperative hospital stay (3 days vs. 3 days, P = 0.305) or total medical costs (26,936 vs. 26,549, P = 0.144). CONCLUSION: Compared to conventional open surgery, fs-TAT offered excellent safety and acceptable short-term oncological outcomes in a selected cohort of patients with papillary thyroid microcarcinoma.


Subject(s)
Thyroid Neoplasms , Thyroidectomy , Humans , Thyroidectomy/methods , Retrospective Studies , Propensity Score , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Endoscopy/methods
7.
Front Endocrinol (Lausanne) ; 14: 1147313, 2023.
Article in English | MEDLINE | ID: mdl-37143719

ABSTRACT

Background: Endoscopic thyroidectomy (ET) via gasless unilateral axillary (GUA) approach has been widely implemented worldwide. Based on our concept of mesothyroid excision in open surgery, we proposed a novel anatomy-based five-settlement method in ET via the GUA approach. This preliminary report aimed to explore the efficacy and safety of this method in patients with papillary thyroid carcinoma (PTC). Methods: PTC patients who underwent endoscopic ET and unilateral central compartment neck dissection (CCND) via GUA approach with the five-settlement method at the Department of General Surgery, Nanfang Hospital, Southern Medical University from March 2020 to December 2021 were retrospectively collected. The data included general clinicopathological characteristics, surgical information (including duration, complication, and clinicopathological features), and hospital stay information, and other medical records were documented. Results: In total, 521 patients underwent lobectomy and CCND under the GUA approach with the five-settlement method. The mean number of lymph nodes yielded (LNY) and positive lymph nodes (PLN) was 5.7 ± 4.3 (range, 1-30) and 1.0 ± 1.8 (range, 0-12), respectively. The incidence of transient recurrent laryngeal nerve injury was 1.1%. Chyle leakage and Horner's syndrome respectively occurred in one patient (0.2%). Five (0.9%) patients developed a hematoma. No severe complications or conversion to open surgery have occurred. Conclusion: The five-settlement method could be implemented safely and efficiently in ET+CCND via the GUA approach in selected PTC patients.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Humans , Thyroidectomy/adverse effects , Thyroidectomy/methods , Thyroid Neoplasms/surgery , Thyroid Neoplasms/pathology , Neck Dissection/adverse effects , Neck Dissection/methods , Retrospective Studies , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology
8.
Int J Surg ; 109(5): 1264-1270, 2023 May 01.
Article in English | MEDLINE | ID: mdl-37080561

ABSTRACT

BACKGROUND: This study aimed to evaluate the relationship between lateral lymph node yield (LLNY) and the ratio of lateral positive lymph nodes to lymph node yield (LPLR) from initial lateral neck dissection (LND) in patients with papillary thyroid carcinoma (PTC), as well as the risk of recurrence in patients undergoing LND reoperations. METHODS: This retrospective cohort study enrolled patients with PTC who underwent revision LND between 1 January 2012, and 31 December 2021. The initial and revised clinical data were retrieved. Patient demographics, clinicopathological features, clinical records, and follow-up information were also reviewed. LLNY and LPLR were determined during the initial LND. RESULTS: In total, 156 patients with PTC were included in this study, with a median follow-up of 36.5 months; 107 had recurrent lateral neck disease. The optimal LLNY and LPLR cutoff values for recurrent/persistent disease were 24.5 and 32.74%, respectively. The high-risk group (LLNY<25) had the lowest recurrence-free survival rate compared with to moderate-risk group (LLNY≥25, LPLR≥32.74%) and low-risk group (LLNY≥25, LPLR<32.74%) ( P <0.001). The moderate-risk group had lower recurrence-free survival than the low-risk group. Multivariate analysis revealed that an LLNY less than 25 in the initial LND was an independent risk factor for recurrence/persistence of lateral neck ( P <0.001). CONCLUSIONS: This study identified that LLNY and LPLR were associated with recurrence/persistence in PTC patients at the time of revision surgery was performed.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Humans , Neck Dissection/adverse effects , Thyroid Cancer, Papillary/surgery , Thyroid Cancer, Papillary/pathology , Cohort Studies , Retrospective Studies , Reoperation/adverse effects , Thyroid Neoplasms/pathology , Carcinoma, Papillary/surgery , Carcinoma, Papillary/pathology , Neoplasm Recurrence, Local/epidemiology , Neoplasm Recurrence, Local/surgery , Thyroidectomy/adverse effects , Lymphatic Metastasis/pathology , Lymph Nodes/surgery , Lymph Nodes/pathology
9.
Redox Biol ; 61: 102642, 2023 05.
Article in English | MEDLINE | ID: mdl-36863169

ABSTRACT

Identifying direct substrates of enzymes has been a long-term challenge. Here, we present a strategy using live cell chemical cross-linking and mass spectrometry to identify the putative substrates of enzymes for further biochemical validation. Compared with other methods, our strategy is based on the identification of cross-linked peptides supported by high-quality MS/MS spectra, which eliminates false-positive discoveries of indirect binders. Additionally, cross-linking sites allow the analysis of interaction interfaces, providing further information for substrate validation. We demonstrated this strategy by identifying direct substrates of thioredoxin in both E. coli and HEK293T cells using two bis-vinyl sulfone chemical cross-linkers BVSB and PDES. We confirmed that BVSB and PDES have high specificity in cross-linking the active site of thioredoxin with its substrates both in vitro and in live cells. Applying live cell cross-linking, we identified 212 putative substrates of thioredoxin in E. coli and 299 putative S-nitrosylation (SNO) substrates of thioredoxin in HEK293T cells. In addition to thioredoxin, we have shown that this strategy can be applied to other proteins in the thioredoxin superfamily. Based on these results, we believe future development of cross-linking techniques will further advance cross-linking mass spectrometry in identifying substrates of other classes of enzymes.


Subject(s)
Oxidoreductases , Protein Interaction Mapping , Tandem Mass Spectrometry , Humans , Escherichia coli/metabolism , HEK293 Cells , Oxidoreductases/metabolism , Tandem Mass Spectrometry/methods , Thioredoxins/metabolism , Protein Interaction Mapping/methods
10.
G3 (Bethesda) ; 13(4)2023 04 11.
Article in English | MEDLINE | ID: mdl-36735812

ABSTRACT

Abnormal nuclear morphology is suggested to be a hallmark of aging and one such abnormality is nuclear blebbing. However, little is known about whether and how nuclear blebbing participates in animal aging, and what regulates it. In this study, we show that the frequency of nuclear blebbing in the hypodermis increases during aging in wild-type C. elegans. These nuclear blebs are enveloped by the nuclear lamina, the inner and the outer nuclear membrane, and 42% of them contain chromatin. Although nuclear blebbing could lead to DNA loss if chromatin-containing blebs detach and fuse with lysosomes, we find by time-lapse imaging that nuclear blebs rarely detach, and the estimated lifetime of a nuclear bleb is 772 h or 32 days. The amount of DNA lost through nuclear blebbing is estimated to be about 0.1% of the total DNA loss by adult Day 11. Furthermore, the frequency of nuclear blebbing does not correlate with the rate of aging in C. elegans. Old age does not necessarily induce nuclear blebbing, neither does starvation, heat stress, or oxidative stress. Intriguingly, we find that proliferation of germ cells promotes nuclear blebbing.


Subject(s)
Caenorhabditis elegans Proteins , Caenorhabditis elegans , Animals , Caenorhabditis elegans/genetics , Caenorhabditis elegans Proteins/genetics , Cell Proliferation , Chromatin/genetics , Germ Cells
11.
Anal Chem ; 95(2): 846-853, 2023 01 17.
Article in English | MEDLINE | ID: mdl-36595388

ABSTRACT

Post-translational modification of proteins by Ubiquitin (Ub) and Ubiquitin-like proteins (Ubls) can be reversed by deconjugating enzymes, which have been implicated in different pathways and associated with various human diseases. To understand the activity and dynamics of deconjugating enzymes, multiple synthetic and semi-synthetic Ub/Ubl probes have been developed, and some of them have been applied to screen inhibitors of deconjugating enzymes. Since these Ub/Ubl probes are generally not cell-permeable, different strategies have been developed to deliver Ub/Ubl probes to live cells. However, till now, no Ub/Ubl probes can be expressed in live cells to directly report on the activities of deconjugating enzymes in the most relevant cellular environment. Here, we genetically encoded cross-linkable Ub/Ubl probes in live E. coli and HEK293T cells. These probes can cross-link with deconjugating enzymes in vitro and in vivo. Using these Ub probes combined with mass spectrometry, we have successfully identified endogenous deconjugating enzymes in live cells. We believe that these genetically encoded Ub/Ubl probes are valuable for investigating biological functions of deconjugating enzymes in physiological environments.


Subject(s)
Ubiquitin , Ubiquitins , Humans , Ubiquitin/chemistry , Escherichia coli/genetics , Escherichia coli/metabolism , HEK293 Cells , Protein Processing, Post-Translational
12.
Front Chem ; 10: 815991, 2022.
Article in English | MEDLINE | ID: mdl-35252115

ABSTRACT

Genetically encoded non-canonical amino acids (ncAAs) with electrophilic moieties are excellent tools to investigate protein-protein interactions (PPIs) both in vitro and in vivo. These ncAAs, including a series of alkyl bromide-based ncAAs, mainly target cysteine residues to form protein-protein cross-links. Although some reactivities towards lysine and tyrosine residues have been reported, a comprehensive understanding of their reactivity towards a broad range of nucleophilic amino acids is lacking. Here we used a recently developed OpenUaa search engine to perform an in-depth analysis of mass spec data generated for Thioredoxin and its direct binding proteins cross-linked with an alkyl bromide-based ncAA, BprY. The analysis showed that, besides cysteine residues, BprY also targeted a broad range of nucleophilic amino acids. We validated this broad reactivity of BprY with Affibody/Z protein complex. We then successfully applied BprY to map a binding interface between SUMO2 and SUMO-interacting motifs (SIMs). BprY was further applied to probe SUMO2 interaction partners. We identified 264 SUMO2 binders, including several validated SUMO2 binders and many new binders. Our data demonstrated that BprY can be effectively used to probe protein-protein interaction interfaces even without cysteine residues, which will greatly expand the power of BprY in studying PPIs.

13.
Curr Med Sci ; 41(6): 1192-1197, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34846700

ABSTRACT

OBJECTIVE: Lymphatic endothelial cell (LEC) proliferation is essential for lymphangiogenesis. Hypoxia induces lymphangiogenesis, but it directly inhibits LEC proliferation and the underlying mechanisms have not been fully understood. The aim of this study was to investigate the role of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in hypoxia-repressed LEC proliferation. METHODS: Human dermal lymphatic endothelial cells (HDLECs) were cultured under normoxic or hypoxic conditions, and cell proliferation was determined using MTT or CCK-8 assays. CEACAM1 expression was silenced by siRNA transfection. Activation of mitogen-activated protein kinases (MAPKs) was examined by Western blotting and blocked by specific inhibitors. RESULTS: Under hypoxia, HDLECs proliferation was suppressed and CEACAM1 expression was downregulated. Silence of CEACAM1 in normoxia inhibited HDLECs proliferation and did not further decrease proliferation in HDLECs in response to hypoxia, suggesting that CEACAM1 may mediate hypoxia-induced inhibition of HDLECs proliferation. In addition, silence of CEACAM1 increased phosphorylation of MAPK molecules: extracellular signal-regulated kinase (ERK), p38 MAPK and Jun N-terminal kinase (JNK) in HDLECs. However, only inhibition of the JNK pathway rescued the reduction of HDLEC proliferation induced by CEACAM1 silence. CONCLUSION: Our results suggested that hypoxia downregulates CEACAM1 expression by activation of the JNK pathway, leading to inhibition of HDLEC proliferation. These findings may help to understand the mechanisms of LEC-specific response to hypoxia and develop novel therapies for pathological lymphangiogenesis.


Subject(s)
Carcinoembryonic Antigen/metabolism , Cell Adhesion Molecule-1/metabolism , Cell Proliferation , Down-Regulation , Endothelial Cells/metabolism , Hypoxia/metabolism , Antigens, CD , Cell Adhesion Molecules , Cell Culture Techniques , Endothelium, Lymphatic , Humans , JNK Mitogen-Activated Protein Kinases/metabolism , Lymphangiogenesis , MAP Kinase Signaling System , Mitogen-Activated Protein Kinases/genetics , Phosphorylation
14.
Oral Oncol ; 123: 105567, 2021 12.
Article in English | MEDLINE | ID: mdl-34710736

ABSTRACT

BACKGROUND: To evaluate the relationship between lymph node yield (LNY) from the initial central neck dissection (CND) and the risk of recurrence in patients undergoing reoperative CND for papillary thyroid cancer (PTC). METHOD: We reviewed clinical data from all patients with pathologically proven PTC who underwent central neck and/or lateral neck dissection reoperations at Nanfang Hospital between 2012 and 2020. Patient demographics, tumor characteristics, clinical data and follow-up information were obtained. In the initial CND, the total number of lymph nodes removed (LNY), total positive nodes removed, and the percentage of positive lymph nodes to the number of lymph nodes removed (PLN%) were determined. RESULTS: A total of 162 patients were included in the study, with a median follow-up of 44 months. 62 had central neck disease recurrence. The optimal LNY and PLN% cut-off values for recurrence were 11 and 65%, respectively. Group 2 (LNY ≥ 11, PLN% < 65%) showed a significantly higher RFS rate than group 1 (LNY < 11 and PLN% < 65%; P < 0.001), group 3 (LNY < 11, PLN% ≥ 65%; P < 0.001), and group 4 (LNY ≥ 11, PLN% ≥ 65%; P = 0.038). Furthermore, group 4 had a higher RFS rate than group 1 (P = 0.008) and group 3 (P = 0.001). Multivariate analysis revealed that LNY < 11 in the central neck was an independent risk factor for recurrence/persistence in the initial surgery (P < 0.001). CONCLUSION: Higher LNY in central and neck dissections is associated with lower papillary thyroid cancer recurrence rates, which was confirmed by a reoperative CND procedure. To minimize the risk of recurrence and the need for secondary therapy, surgeons should perform compartment-oriented CNDs when indicated.


Subject(s)
Carcinoma, Papillary , Thyroid Neoplasms , Carcinoma, Papillary/pathology , Carcinoma, Papillary/surgery , Cohort Studies , Humans , Lymph Nodes/pathology , Lymph Nodes/surgery , Lymphatic Metastasis/pathology , Neck Dissection/methods , Neoplasm Recurrence, Local/pathology , Retrospective Studies , Thyroid Cancer, Papillary/pathology , Thyroid Cancer, Papillary/surgery , Thyroid Neoplasms/pathology , Thyroid Neoplasms/surgery , Thyroidectomy/methods
15.
Mol Ecol Resour ; 21(6): 2077-2092, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33825319

ABSTRACT

There are wide genomic and phenotypic differences between Asian and European pig breeds, yet the current reference genome is the European Duroc pig genome. A high-quality pig genome is lacking for genetic analysis of agricultural traits in Asian pigs. Here, using a hybrid approach, a high-quality reference genome (MSCAAS v1) for the Asian Meishan breed is assembled with a contig N50 size of 48.05 Mb. MSCAAS v1 outperforms the Duroc genome as a reference genome for Asian breeds. Genomic comparison reveals 49,103 structural variations (SVs) between Meishan and Duroc, 4.02% of which are Asian-specific SVs (AP-SVs). Notably, a 30-Mb hotspot for AP-SVs on chromosome X enriched for genes associated with Asian-pig-specific phenotypes is present in Asian domestic pig breeds, but absent in Asian wild boars, suggesting that Asian domestic breeds share a common ancestor. Interbreed transcriptomics reveals transcriptional suppression roles of AP-SVs in multiple tissues. Finally, transcriptional regulation in the intron of IGF2R is reported, as genomic SV (274-bp deletion) in Tibetan pig limits its growth compared to domestic pig breeds. In summary, this study provides insights regarding the genetic changes underlying pig domestication and presents a benchmark-setting resource for the utilization of agricultural valuable loci in Asian pigs.


Subject(s)
Domestication , Genome , Swine , Animals , Gene Expression , Genomics , Phenotype , Swine/genetics
16.
Adv Biol (Weinh) ; 5(3): e2000308, 2021 03.
Article in English | MEDLINE | ID: mdl-33729691

ABSTRACT

Protein crosslinks occur endogenously such as modifications by ubiquitin-like proteins for signaling, or exogenously through genetically encoded chemical crosslinkers (GECX) for studying elusive protein-protein interactions. However, it remains challenging to identify these protein crosslinks efficiently at the proteomic scale. Herein, software OpenUaa is developed for identifying protein crosslinks generated by genetically encoded unnatural amino acids and endogenous protein conjugation. OpenUaa features inclusive and open search capability, dramatically improving identification sensitivity and coverage. Integrating GECX with OpenUaa, the direct interactome of thioredoxin is identified in Escherichia coli cells, yielding 289 crosslinked peptides and corresponding to 205 direct binding protein of thioredoxin. These identified direct binders provide evidence for thioredoxin's regulation of redox state and mitochondria energy metabolism. When identifying endogenous conjugation of small ubiquitin-like modifier (SUMO), OpenUaa also markedly improves coverage of SUMOylated peptides by ≈92%, revealing new SUMO targets. GECX-OpenUaa will enable efficient identification of direct interactomes of various proteins in live cells.


Subject(s)
Proteomics , Search Engine , Genetic Code , Ubiquitin , Ubiquitins
17.
Article in English | MEDLINE | ID: mdl-32982961

ABSTRACT

In our previous study, we have shown that CRLF1 can promote proliferation and metastasis of papillary thyroid carcinoma (PTC); however, the mechanism is unclear. Herein, we investigated whether the interaction of CRLF1 and MYH9 regulates proliferation and metastasis of PTC cells via the ERK/ETV4 axis. Immunohistochemistry (IHC), qPCR, and Western blotting assays were performed on PTC cells and normal thyroid cells to profile specific target genes. In vitro assays and in vivo assays were also conducted to examine the molecular mechanism. Results showed that CRLF1 directly bound MYH9 to enhance the stability of CRLF1 protein. Inhibition of MYH9 in PTC cells overexpressing CRLF1 significantly reversed malignant phenotypes, and CRLF1 overexpression activated ERK pathway, in vitro, and in vivo. RNA-sequencing revealed that ETV4 is a downstream target gene of CRLF1, which was up-regulated following ERK activation. Moreover, it was revealed that ETV4 is highly expressed in PTC tissues and is associated with poor prognosis. Finally, the ChIP assays showed that ETV4 induces the expression of matrix metalloproteinase 1 (MMP1) by binding to its promoter on PTC cells. Altogether, our study demonstrates that CRLF1 interacts with MYH9, promoting cell proliferation and metastasis via the ERK/ETV4 axis in PTC.


Subject(s)
Biomarkers, Tumor/metabolism , Cell Proliferation , MAP Kinase Signaling System , Myosin Heavy Chains/metabolism , Proto-Oncogene Proteins c-ets/metabolism , Receptors, Cytokine/metabolism , Thyroid Cancer, Papillary/secondary , Adolescent , Adult , Aged , Animals , Apoptosis , Biomarkers, Tumor/genetics , Female , Gene Expression Regulation, Neoplastic , Humans , Male , Mice , Mice, Inbred BALB C , Mice, Nude , Middle Aged , Myosin Heavy Chains/genetics , Prognosis , Protein Interaction Domains and Motifs , Proto-Oncogene Proteins c-ets/genetics , Receptors, Cytokine/genetics , Survival Rate , Thyroid Cancer, Papillary/genetics , Thyroid Cancer, Papillary/metabolism , Thyroid Neoplasms/genetics , Thyroid Neoplasms/metabolism , Thyroid Neoplasms/pathology , Tumor Cells, Cultured , Xenograft Model Antitumor Assays , Young Adult
18.
Gland Surg ; 9(2): 474-477, 2020 Apr.
Article in English | MEDLINE | ID: mdl-32420277

ABSTRACT

Primary squamous cell carcinoma (PSCC) is a rare neoplasm of the thyroid with a very poor prognosis. We report a case of a 42-year-old woman with occasionally found mass in the right anterior area of the neck. After a total thyroidectomy, histopathology and immunohistochemistry tests confirmed primary squamous cell carcinoma of the thyroid with the exclusion of all other possible primary tumor locations. 5 months later, PET scan discovered abnormality in right cervical lymph nodes with a fine needle aspiration confirming to be tumor recurrence. After a modified radical neck dissection was performed with pathological results of the neoplasms being PSCC of the thyroid origin, a full course consecutive radiotherapy was then followed. Due to a prompt diagnosis and the complete dissection of primary tumor and metastatic lymph nodes, no recurrence was observed at the follow-up visits. Comparing to the published cases of PSCC of the thyroid, our paper stated a whole process of diagnosis and standardized treatment, together with classical matched figures of pre-op examinations and dissected specimen. Furthermore, a review of the present literatures summarized the diagnosis, treatment and prognosis of thyroid PSCC. The management of PSCC requires a multi-disciplinary approach.

19.
Eur J Surg Oncol ; 45(11): 2086-2089, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31395292

ABSTRACT

BACKGROUND: The objective of the current study was to investigate the clinical significance of the suprasternal space lymph node (SSLN) in pathological node-positive (pN+) papillary thyroid carcinoma (PTC) patients. METHOD: One hundred and forty patients with pN + PTC who underwent neck dissection were enrolled into this study. SSLN was resected and used as a specimen to investigate the relationship of SSLN with several clinicopathological parameters. RESULTS: The metastasis rate of SSLN was 20.7%. On univariate analysis, we found that SSLN metastasis was significantly associated with primary cancer site (inferior portion), strap muscle invasion, level III metastasis, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles. On multivariate analysis, primary cancer site (inferior portion), strap muscle invasion, Level IV metastasis and lymph node metastasis between sternocleidomastoid and sternohyoid muscles were independent risk factors for SSLN metastasis of PTC. CONCLUSION: For pN + PTC patients, special attention should be paid to the issue of SSLN metastasis.


Subject(s)
Lymph Nodes/pathology , Neck Muscles/pathology , Thyroid Cancer, Papillary/pathology , Thyroid Neoplasms/pathology , Female , Humans , Lymphatic Metastasis , Male , Middle Aged , Multivariate Analysis , Neck Dissection , Neoplasm Invasiveness , Neoplasm Staging , Retrospective Studies , Risk Factors , Sternum , Thyroid Cancer, Papillary/surgery , Thyroid Neoplasms/surgery
20.
Front Oncol ; 9: 312, 2019.
Article in English | MEDLINE | ID: mdl-31134145

ABSTRACT

Background: Epstein-Barr virus (EBV) is associated with many epithelial malignancies. A few reports on the association between EBV and thyroid tumorigenesis have been investigated. However, the conclusion is highly contradictory. We aimed to explore the role of EBV in thyroid nodule development and its clinical significance in a cohort from southern China. Method: We conducted a retrospective data abstraction study of patients who underwent thyroidectomy between December 2017 and June 2018. We retrospectively analyzed the clinicopathological parameters and EBV infection status (serological antibodies and in situ hybridization). Result: The cohort comprised 384 patients with newly diagnosed thyroid diseases, including 261 papillary thyroid carcinomas, 87 nodular goiters, 21 follicular adenomas, 12 follicular thyroid carcinomas, and 3 medullary thyroid carcinomas. Forty-two (10.9%) patients were identified as being serological antibody positive. However, there was no association between the clinicopathological parameters and serological antibody positivity. Additionally, none of the patients showed EBER expression in thyroid normal/cancer cell nuclei in in situ hybridization. Conclusion: In this study, no correlation between EBV and thyroid diseases was found in a cohort from southern China.

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