A copy of this work was available on the public web and has been preserved in the Wayback Machine. The capture dates from 2021; you can also visit the original URL.
The file type is
The immune system's ability to resist the invasion of foreign pathogens and the tolerance to self-antigens are primarily centered on the efficient functions of the various subsets of T lymphocytes. As the primary organ of thymopoiesis, the thymus performs a crucial role in generating a self-tolerant but diverse repertoire of T cell receptors and peripheral T cell pool, with the capacity to recognize a wide variety of antigens and for the surveillance of malignancies. However, cells in thedoi:10.3389/fimmu.2021.706244 pmid:34539637 pmcid:PMC8442952 fatcat:wa7tvc7tsbeqxfig5irni6frpm
more »... are fragile and sensitive to changes in the external environment and acute insults such as infections, chemo- and radiation-therapy, resulting in thymic injury and degeneration. Though the thymus has the capacity to self-regenerate, it is often insufficient to reconstitute an intact thymic function. Thymic dysfunction leads to an increased risk of opportunistic infections, tumor relapse, autoimmunity, and adverse clinical outcome. Thus, exploiting the mechanism of thymic regeneration would provide new therapeutic options for these settings. This review summarizes the thymus's development, factors causing thymic injury, and the strategies for improving thymus regeneration.
Myasthenia gravis (MG) is an autoimmune disease caused by the transmission of dysfunction in the neuromuscular junction, manifesting partial or systemic skeletal muscle weakness and fatigue, which are exacerbated by activities and relieved after rest. Currently, the conventional therapy is applying cholinesterase inhibitors, steroids, immunosuppressant, and thymectomy. However, these drugs have obvious side effects. According to traditional Chinese medicine (TCM) theory, Buzhong Yiqi decoctiondoi:10.1097/md.0000000000013677 pmid:30558075 pmcid:PMC6320065 fatcat:t4adpj6k75gctbmwndgrbjm75a
more »... BYD) is a Qi-supplementing formula which is suitable for MG management as MG is generally diagnosed as "flaccidity syndrome" and considered caused by Qi-deficiency. An increasing number of clinical controlled studies also have found that BYD could improve the efficacy and reduced adverse effects in treating MG, but there is no systematic review of it. Therefore, we will use meta-analysis to evaluate the efficacy and safety of BYD for MG. PubMed, MEDLINE, EMBASE, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang data, Chinese Scientific Journals Database (VIP), and China biomedical literature database (CBM) will be searched to obtain the eligible studies published up to June 1, 2018. The primary outcome will be clinical absolute score before and after treatment, clinical relative score as well as effective rate. The secondary outcome will be the concentration of acetylcholine receptor antibody (AchRAb) in serum and adverse events incidence. Data analysis will be conducted using RevMan5.3 and Stata V.9.0 software. Trial sequential analysis (TSA) will be performed to assess the risk of random error and the validity of conclusion using TSA program version 0.9 beta. This systematic review will provide a high-quality synthesis of BYD and its modified forms for MG from various evaluation aspects including clinical absolute score before and after treatment, clinical relative score, effective rate, the concentration of AchRAb in serum and adverse events incidence. The systematic review will provide evidence to assess the efficacy and safety of BYD and its modified forms in the treatment of MG. PROSPERO CRD42018095241.
Since more than one hundred events of genetically modified organisms (GMOs) have been developed and approved for commercialization in global area, the GMO analysis methods are essential for the enforcement of GMO labelling regulations. Protein and nucleic acidbased detection techniques have been developed and utilized for GMOs identification and quantification. However, the information for harmonization and standardization of GMO analysis methods at global level is needed. Results: GMOdoi:10.1186/1471-2105-9-260 pmid:18522755 pmcid:PMC2430717 fatcat:uvwfcddvsvcsbjrofbpg3rrztu
more »... method Database (GMDD) has collected almost all the previous developed and reported GMOs detection methods, which have been grouped by different strategies (screen-, gene-, construct-, and event-specific), and also provide a user-friendly search service of the detection methods by GMO event name, exogenous gene, or protein information, etc. In this database, users can obtain the sequences of exogenous integration, which will facilitate PCR primers and probes design. Also the information on endogenous genes, certified reference materials, reference molecules, and the validation status of developed methods is included in this database. Furthermore, registered users can also submit new detection methods and sequences to this database, and the newly submitted information will be released soon after being checked. Conclusion: GMDD contains comprehensive information of GMO detection methods. The database will make the GMOs analysis much easier.
Genome integrity is essential for normal cellular functions and cell survival. Its instability can cause genetic aberrations and is considered as a hallmark of most cancers. To investigate the carcinogenesis process induced by tobacco-specific carcinogen NNK, we studied the dynamic changes of two important protectors of genome integrity, p53 and MMR system, in malignant transformation of human bronchial epithelial cells after NNK exposure. Our results showed that the expression of MLH1, one ofdoi:10.1155/2014/920275 pmid:25215298 pmcid:PMC4151862 fatcat:pfazze64crdrllr5ivmwnsluzy
more »... he important MMR proteins, was decreased early and maintained the downregulation during the transformation in a histone modification involved and DNA methylation-independent manner. Another MMR protein PMS2 also displayed a declined expression while being in a later stage of transformation. Moreover, we conducted p53 mutation analysis and revealed a mutation at codon 273 which led to the replacement of arginine by histidine. With the mutation, DNA damage-induced activation of p53 was significantly impaired. We further reintroduced the wild-type p53 into the transformed cells, and the malignant proliferation can be abrogated by inducing cell cycle arrest and apoptosis. These findings indicate that p53 and MMR system play an important role in the initiation and progression of NNK-induced transformation, and p53 could be a potential therapeutic target for tobacco-related cancers.
BMC Plant Biology
Background Brassica juncea behaves as a moderate-level accumulator of various heavy metal ions and is frequently used for remediation. To investigate the roles of metal ion transporters in B. juncea, a cation-efflux family gene, BjCET1, was cloned and functionally characterized. Results BjCET1 contains 382 amino acid residues, including a signature motif of the cation diffusion facilitator protein family, six classic trans-membrane-spanning structures and a cation-efflux domain. A phylogeneticdoi:10.1186/s12870-022-03569-x pmid:35387616 pmcid:PMC8985314 fatcat:pks2gue7gbgcfi6rumz3qt3jja
more »... nalysis showed that BjCET1 has a high similarity level with metal tolerance proteins from other Brassica plants, indicating that this protein family is highly conserved in Brassica. BjCET1 expression significantly increased at very early stages during both cadmium and zinc treatments. Green fluorescence detection in transgenic tobacco leaves revealed that BjCET1 is a plasma membrane-localized protein. The heterologous expression of BjCET1 in a yeast mutant increased the heavy-metal tolerance and decreased the cadmium or zinc accumulations in yeast cells, suggesting that BjCET1 is a metal ion transporter. The constitutive expression of BjCET1 rescued the heavy-metal tolerance capability of transgenic tobacco plants. Conclusions The data suggest that BjCET1 is a membrane-localized efflux transporter that plays essential roles in heavy metal ion homeostasis and hyper-accumulation.
Epigenetic abnormalities contribute significantly to the development and progression of gastric cancer. However, the underlying regulatory networks from oncogenic signaling pathway to epigenetic dysregulation remain largely unclear. Here we showed that STAT3 signaling, one of the critical links between inflammation and cancer, acted as a control pathway in gastric carcinogenesis. STAT3 aberrantly transactivates the epigenetic kinase mitogen- and stress-activated protein kinase 1 (MSK1), therebydoi:10.1038/s41389-020-0195-2 pmid:32041943 pmcid:PMC7010763 fatcat:kystv6r23ffr3fka5zpxteztqm
more »... phosphorylating histone H3 serine10 (H3S10) and STAT3 itself during carcinogen-induced gastric tumorigenesis. We further identified the calcium pathway transcription factor NFATc2 as a novel downstream target of the STAT3-MSK1 positive-regulating loop. STAT3 forms a functional complex with MSK1 at the promoter of NFATc2 to promote its transcription in a H3S10 phosphorylation-dependent way, thus affecting NFATc2-related inflammatory pathways in gastric carcinogenesis. Inhibiting the STAT3/MSK1/NFATc2 signaling axis significantly suppressed gastric cancer cell proliferation and xenograft tumor growth, which provides a potential novel approach for gastric carcinogenesis intervention by regulating aberrant epigenetic and transcriptional mechanisms.
Background Zinc finger protein 143(ZNF143), a member of the Krüppel C2H2-type zinc finger protein family, is strongly associated with cell cycle regulation and cancer development. A recent study suggested that ZNF143 plays as a transcriptional activator that promotes hepatocellular cancer (HCC) cell proliferation and cell cycle transition. However, the exact biological role of ZNF143 in liver regeneration and normal liver cell proliferation has not yet been investigated. Methods In our study,doi:10.1186/s12864-022-08714-2 pmid:35780101 pmcid:PMC9250731 fatcat:af3pg2xhyzbjllomap7jcxdx6q
more »... constructed a stable rat liver cell line (BRL-3A) overexpressing ZNF143 and then integrated RNA-seq and Cleavage Under Targets and Tagmentation (CUT&Tag) data to identify the mechanism underlying differential gene expression. Results Our results show that ZNF143 expression is upregulated during the proliferation phase of liver regeneration after 2/3 partial hepatectomy (PH). The cell counting kit-8 (CCK-8) assay, EdU staining and RNA-seq data analyses revealed that ZNF143 overexpression (OE) significantly inhibited BRL-3A cell proliferation and cell cycle progression. We then performed CUT&Tag assays and found that approximately 10% of ZNF143-binding sites (BSs) were significantly changed genome-wide by ZNF143 OE. However, CCCTC-binding factor (CTCF) binding to chromatin was not affected. Interestingly, the integration analysis of RNA-seq and CUT&Tag data showed that some of genes affected by ZNF143 differential BSs are in the center of each gene regulation module. Gene ontology (GO) enrichment and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analyses indicated that these genes are critical in the maintenance of cell identity. Conclusion These results indicated that the expression level of ZNF143 in the liver is important for the maintenance of cell identity. ZNF143 plays different roles in HCC and normal liver cells and may be considered as a potential therapeutic target in liver disease.
Rationale: Situs inversus totalis (SIT) is a rare congenital anomaly characterized by complete inversion of the abdominal and thoracic organs, and often involves multiple genetic mutations. The most suitable surgical technique for patients with multiple vessel and organ variations as well as SIT remains unclear. Furthermore, there has been insufficient clinical evidence that demonstrates which surgical techniques achieve the best outcomes. Finally, the standard of care has not yet beendoi:10.1097/md.0000000000008209 pmid:28953685 pmcid:PMC5626328 fatcat:wncsuwq2ufhfhksaxb5qlaswbu
more »... d. We present the case of a 60-year-old man with SIT, who was diagnosed with moderately and poorly differentiated adenocarcinoma at the gastroesophageal junction. We further describe the advantage of using robotic-assisted laparoscopic surgery in patients with this anomaly. Patient concerns: A 60-year-old man complained of pain in his upper abdomen for 3 months. Physical examination revealed an apex beat in the right fifth intercostal space, and vascular anomalies were noted on abdominal angiographic computed tomography. Diagnoses: Moderately and poorly differentiated adenocarcinoma at the gastroesophageal junction with SIT. Interventions: Robot-assisted total gastrectomy with D2 lymph node dissection and hand-sewn Roux-en-Y anastomosis was performed. Outcomes: The postoperative course was uneventful, and the patient was discharged on the seventh postoperative day. Lessons: Robotic surgery for gastric cancer is a safe and feasible alternative to laparoscopic surgery and it can be successfully used to treat gastric cancer in patients with SIT with multiple anatomic variations. As exemplified by our case, SIT might be accompanied by multiple anatomic variations. Detailed preoperative detailed imaging of the blood vessels and gastrointestinal tract is useful in these patients. Abbreviations: ALHA = accessory left hepatic artery, GDA = gastroduodenal artery, HA = hepatic artery, LADG = laparoscopicassisted distal gastrectomy, LGA = left gastric artery, SIT = situs inversus totalis, SMA = superior mesenteric artery, SPA = splenic artery, SPV = splenic vein.
Wood–plastic composites (WPC) with good mechanical and physical properties are desirable products for manufacturers and customers, and interfacial bond strength is one of the most critical factors affecting WPC performance. To verify that a higher interfacial bond strength between wood and thermoplastics improves WPC performance, wood veneer–thermoplastic composites (VPC) and oriented strand–thermoplastic composites (OSPC) were fabricated using hot pressing. The effects of the coupling agentdoi:10.3390/polym13234260 pmid:34883763 fatcat:2zvelk3gxncczj5uvkappdlyiu
more »... 550 or MDI) and the thermoplastic (LDPE, HDPE, PP, or PVC) on the interfacial bond strength of VPC, and the mechanical and physical properties of OSPC, were investigated. The results showed that coupling agents KH550 and MDI improved the interfacial bond strength between wood and thermoplastics under dry conditions. MDI was better than KH550 at improving the interfacial bond strength and the mechanical properties of OSPC. Better interfacial bonding between plastic and wood improved the OSPC performance. The OSPC fabricated using PVC film as the thermoplastic and MDI as the coupling agent displayed the highest mechanical properties, with a modulus of rupture of 91.9 MPa, a modulus of elasticity of 10.9 GPa, and a thickness swelling of 2.4%. PVC and MDI are recommended to fabricate WPCs with desirable performance for general applications.
Originating from extranodal organs or tissues, primary extranodal lymphoma (PENL) acts in different primary sites with diverse clinical performances and PENL has remarkable geographical differences and lacks the relevant reports in each region. Two hundred and twenty PENL patients were enrolled, and the relevant clinical and laboratory indicators were analyzed. In addition, statistical methods were applied to analyze the effects of different factors on overall survival (OS) and progression-freedoi:10.2147/cmar.s299745 pmid:33688260 pmcid:PMC7936719 fatcat:yeyfwdf7c5henpw7e6rhxygprq
more »... survival (PFS) of patients. The three most frequent primary sites of PENL are the digestive system, head and neck, and central nervous system. The patients were classified into groups based on their risk status, resulting in low-risk, medium-low-risk, medium-high-risk, and high-risk, and their respective 3-year OS values were calculated, which showed that 121 patients (55%) were in the low-risk group and 3-year OS was 85.2% (25.9% medium-low-risk, 3-year OS 66.6%; 15% medium-high-risk, 3-year OS 61.9%; 4.09% high risk, 3-year OS 45.7%). A multivariate analysis of the Cox regression demonstrated that serum beta 2-microglobulin (β2-MG) and lactate dehydrogenase (LDH) were independent prognostic factors for OS and PFS, respectively. Both the performance status and pathological subtypes were independent prognostic factors for OS and PFS. The correlated independent risk factors such as β2-MG, LDH, performance status, and pathological subtypes, were helpful for effectively determining the prognosis of PENL patients and guiding treatment.
Liming Shen and Yinghao Cao contributed to the literature search and collection of the data. ... Wen Jiang, Ke Liu, Qing Guo. and Kailin Cai contributed to the study design, literature search, data analysis, and the writing of the manuscript. ...doi:10.18632/oncotarget.17602 pmid:28977947 pmcid:PMC5617507 fatcat:4mmvkwxtk5bezk7lbc5on6nojy
Supplementary Figure. 1: Construction of different "training" and "testing" datasets. There are no overlapped drug pairs between each set of "training" and the corresponding "testing" dataset. Figure. 2: Isobolograms for the 17 agent pairs tested by experiment on MCF7 cell line. The horizontal axis and the vertical axis represent the relative dose of the drugs. The area between the two diagonal dotted gray lines in each plot represents the additive effect, while the triangular region under thisdoi:10.1038/ncomms9481 pmid:26412466 pmcid:PMC4598846 fatcat:szirkmd7tjc4figqlcgaolkox4
more »... additive effect area indicates the synergy effect. Triangular points represent the relative concentrations of the combinations resulting in 50% inhibition of cancer cells. The two drugs were used alone or in combinations at 4 different concentration ratios: 4:1, 3:2, 2:3, and 1:4. Therefore, there were four Triangular points for each drug pair. Figure. 3: Isobolograms for the 30 randomly picked agent pairs tested by experiment on MCF7 cell line. The horizontal axis and the vertical axis represent the relative dose of the drugs. The area between the two diagonal dotted gray lines in each plot represents the additive effect, while the triangular region under this additive effect area indicates the synergy effect. Triangular points represent the relative concentrations of the combinations resulting in 50% inhibition of cancer cells. The two drugs were used alone or in combinations at 4 different concentration ratios: 4:1, 3:2, 2:3, and 1:4. Therefore, there were four Triangular points for each drug pair. Supplementary Figure. 4: Result of the validation experiment for the randomly picked agent pairs on ER positive breast cancer cell line MCF7. Each drug with the corresponding maximum concentration used for the single drug in the experiment was recorded in Drug1# and Drug2#. Supplementary Supplementary The Chou and Talalay median-effect method was used to calculate the CI and summarized in a heat map. Green indicates synergy (CI < 0.9); yellow indicates additive (0.9 1.1). "4+1", "3+2", "2+3", and "1+4" indicate the two drugs were used in combinations at four different concentration ratios: 4:1, 3:2, 2:3, and 1:4. Supplementary Figure. 5: True positive rate, hit-rate, enrichment-factor of the preliminary ranking model of RACS. 10 times cross validation was performed with 10, 15, or 20 positive samples as training sets respectively. The dark dot is the mean value for true positive rate, hit-rate, and enrichment-factor, while the upper bound and lower bound denote the max and min value of them. Supplementary Figure. 6: True positive rate for dataset with 41 positive samples and 5 features. 10 times cross validation was performed with 10, 20, or 30 positive samples as training sets respectively. The dark dot, the upper bound and lower bound represent the mean value, max and min value for true positive rate. 10 positive samples 15 positive samples 20 positive samples Enrichment_factor Our model One-class SVM Supplementary Figure. 10: Assessment of the contribution of individual features and the combined features to model performance. Values are averaged for 10 times. Supplementary Figure. 11: Performance of RACS with different choice of features. The light blue bars denote the performance of RACS using only one single feature, the dark gold ones denote the performance of RACS when one of the 7 significant feature was removed, while the pink bars represent the performance of RACS when one of the 7 insignificant feature was incorporated. Supplementary Figure. 12: Evaluation of RACS performance by sub-selecting drug targets. a. Distribution of drugs with respect to number of their targets. b. Ranking concordance for agents with 2 target proteins. For each of the 33 drugs with 2 target proteins, 117 drug pairs were obtained when combined with the left 117 drugs. The concordance of predicted ranking lists of the 117 drug pairs before and after removing one of the targets were measured using C-index. c. Ranking concordance for agents with 3 target proteins. For each of the 26 drugs with 3 target proteins, the three single targets together with all three 2-targets-combinations were removed respectively each time. The concordance of predicted ranking lists of the 117 drug pairs before and after removing one/two of the targets were measured using C-index. Supplementary Figure. 16: Result of the validation experiment for the bottom ranked agent pairs on NSCLC A549. Each drug with the corresponding maximum concentration used for the single drug in the experiment was recorded in Drug1# and Drug2#. The Chou and Talalay median-effect method was used to calculate the CI and summarized in a heat map. Green indicates synergy (CI < 0.9); yellow indicates additive (0.9 1.1). "4+1", "3+2", "2+3", and "1+4" indicate the two drugs were used in combinations at four different concentration ratios: 4:1, 3:2, 2:3, and 1:4. Supplementary Figure. 17: Maximum non-lethal concentration (MNLC) and LC50 determination of Sorafenib. a. statistic number of animal situations observed after Sorafenib treatment; b. graphic representation of the data from a. Supplementary Figure. 18: Maximum non-lethal concentration (MNLC) and LC50 determination of Tamoxifen. a. statistic number of animal situations observed after Tamoxifen treatment; b. graphic representation of the data from a.
KaiXiong Tao, Guobin Wang, and Kailin Cai contributed to the review and revise of the manuscript. Conceptualization: Yinghao Cao, Guobin Wang. ... Author contributions Shenghe Deng, Liming Shen, Jiang Li, Ke Wu, and Jiliang Wang contributed to the study design, literature search, collection of the data, and data analysis. ...doi:10.1097/md.0000000000011411 pmid:29979440 pmcid:PMC6076044 fatcat:6a27qu32zbaslcybvetjdig2bm
Our previous work have shown that certain subpopulations of Klebsiella pneumoniae exhibit significant phenotypic changes under simulated microgravity (SMG), including enhanced biofilm formation and cellulose synthesis, which may be evoked by changes in gene expression patterns. It is well known that prokaryotic cells genomic DNA can be hierarchically organized into different higher-order three-dimensional structures, which can highly influence gene expression. It is remain elusive whetherdoi:10.3389/fmicb.2022.879321 pmid:35711756 pmcid:PMC9197264 fatcat:zxac6srcjfch3ajagx24eneuou
more »... ypic changes induced by SMG in the subpopulations of K. pneumoniae are driven by genome higher-order structural changes. Here, we investigated the above-mentioned issue using the wild-type (WT) K. pneumoniae (WT was used as a control strain and continuously cultivated for 2 weeks under standard culture conditions of normal gravity) and two previous identified subpopulations (M1 and M2) obtained after 2 weeks of continuous incubation in a SMG device. By the combination of genome-wide chromosome conformation capture (Hi-C), RNA-seq and whole-genome methylation (WGS) analyses, we found that the along with the global chromosome interactions change, the compacting extent of M1, M2 subpopulations were much looser under SMG and even with an increase in active, open chromosome regions. In addition, transcriptome data showed that most differentially expressed genes (DEGs) were upregulated, whereas a few DEGs were downregulated in M1 and M2. The functions of both types DEGs were mainly associated with membrane fractions. Additionally, WGS analysis revealed that methylation levels were lower in M1 and M2. Using combined analysis of multi-omics data, we discovered that most upregulated DEGs were significantly enriched in the boundary regions of the variable chromosomal interaction domains (CIDs), in which genes regulating biofilm formation were mainly located. These results suggest that K. pneumoniae may regulate gene expression patterns through DNA methylation and changes in genome structure, thus resulting in new phenotypes in response to altered gravity.
Background Numerous cytokines have been proven to participate in the pathogenesis of neovascular age-related macular degeneration (nAMD). The present study aimed to investigate the aqueous humor cytokine expression profile in nAMD patients before and after ranibizumab treatments in comparison to cataract patients. Methods This prospective study included 20 treatment-naïve nAMD eyes of 20 patients who received three consecutive monthly injections of ranibizumab. Aqueous humor samples weredoi:10.1186/s12886-020-01684-7 pmid:33115414 pmcid:PMC7592502 fatcat:kwov2g7jh5cqdmuwkvza4dkg6a
more »... ed before the first (baseline), second (1 month later), and third (2 months later) injections. Controls were 20 age- and gender-matched cataract patients without any other ocular disease. The aqueous concentrations of 28 cytokines were measured using a multiplex bead assay. Central macular thickness (CMT) and maximum retinal thickness (MRT)-3 mm were measured by spectral domain optical coherence tomography (SD-OCT). The greatest linear diameter (GLD) was measured by fundus fluorescein angiography (FA). Results Three cytokines in aqueous humor, including angiogenin, interleukin-36β (IL-36β), and fibroblast growth factor-acidic (FGF-α) were significantly higher in nAMD patients in comparison to cataract patients, both before and after two consecutive monthly ranibizumab injections. Compared with the nAMD patients' basal levels, two consecutive monthly ranibizumab injections effectively reduced the aqueous concentrations of VEGF-A and placental growth factor (PlGF), as well as the values of CMT, MRT-3 mm, and GLD. Conclusions Angiogenin, IL-36β, and FGF-α have higher expression levels in nAMD patients in comparison to cataract patients, both before and after 2 months of ranibizumab therapy. These cytokines may have correlations with the pathogenesis of nAMD.
« Previous Showing results 1 — 15 out of 61 results