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1.
Biochem Genet ; 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38568374

ABSTRACT

JAK2-unmutated erythrocytosis or non-polycythemia vera erythrocytosis is a rare condition comprising both acquired and hereditary forms. Although acquired erythrocytosis has been well-studied, hereditary erythrocytosis remains poorly studied. Genetic alterations associated with hereditary erythrocytosis include mutations in erythropoietin receptor and erythropoietin (EPO), altered oxygen affinity mutations, and variants associated with the oxygen-sensing pathway. We established a molecular diagnostic approach based on these genes and retrospectively evaluated. Peripheral blood from 56 erythrocytosis patients, lacking JAK2 mutation, were screened for oxygen-sensing pathway abnormalities. Two novel mutations were identified in the EGLN1 gene: NM_022051.2:c.712G > C (p.Gly238Arg) and NM_022051.2:c.122A > C (p.Tyr41Ser) in two patients separately. Notably, both reported heterozygous mutations were absent in the population database. Predictions using multiple computer software indicated that these two missense mutations were harmful and induced a highly conserved amino acid change in EGLN1. Patients with the two mutations exhibited normal serum EPO levels and high hemoglobin and hematocrit levels. Additionally, three other variants of genes were identified in the oxygen-sensing pathway, including endothelial PAS domain protein 1 (EPAS1) rs184760160(2/56), and EGLN1 rs186996510(2/56), rs555121182(2/56). These variants were categorized as benign or likely benign. Our findings provide a framework for etiological research and highlight the importance of screening for genetic mutations associated with erythrocytosis in clinical practice.

2.
Front Pharmacol ; 15: 1324140, 2024.
Article in English | MEDLINE | ID: mdl-38362156

ABSTRACT

Hepatocellular carcinoma (HCC) is one of the most prevalent cancers worldwide and accounts for more than 90% of primary liver cancer. The advent of immune checkpoint inhibitor (ICI)-related therapies combined with angiogenesis inhibition has revolutionized the treatment of HCC in late-stage and unresectable HCC, as ICIs alone were disappointing in treating HCC. In addition to the altered immune microenvironment, abnormal lipid metabolism in the liver has been extensively characterized in various types of HCC. Stains are known for their cholesterol-lowering properties and their long history of treating hypercholesterolemia and reducing cardiovascular disease risk. Apart from ICI and other conventional therapies, statins are frequently used by advanced HCC patients with dyslipidemia, which is often marked by the abnormal accumulation of cholesterol and fatty acids in the liver. Supported by a body of preclinical and clinical studies, statins may unexpectedly enhance the efficacy of ICI therapy in HCC patients through the regulation of inflammatory responses and the immune microenvironment. This review discusses the abnormal changes in lipid metabolism in HCC, summarizes the clinical evidence and benefits of stain use in HCC, and prospects the possible mechanistic actions of statins in transforming the immune microenvironment in HCC when combined with immunotherapies. Consequently, the use of statin therapy may emerge as a novel and valuable adjuvant for immunotherapies in HCC.

3.
Ther Adv Neurol Disord ; 17: 17562864231219151, 2024.
Article in English | MEDLINE | ID: mdl-38288324

ABSTRACT

Background: Due to the rarity of polyneuropathy, organomegaly, endocrinopathy, monoclonal gammopathy, and skin changes (POEMS) syndrome, the best first-line treatment has not been established, although there are several options in guidelines. The preferred treatments vary according to the preference of the physician and anecdote. Objectives: First, to analyze the efficacy of a new treatment mode in POEMS syndrome that uses the four-cycle treatment as the induction regimen, followed by sequential transplantation as the consolidation regimen for transplantation-eligible patients, or received another two-cycle treatment for transplantation-ineligible patients. Second, to compare the efficacy and safety of regimens with a proteasome inhibitor (bortezomib-cyclophosphamide-dexamethasone, BCD) or without a proteasome inhibitor (cyclophosphamide-dexamethasone ± thalidomide, CD ± T). Design: We conducted a retrospective study using real-world data from Capital Medical University, Xuanwu Hospital. Methods: A total of 34 newly diagnosed POEMS syndrome patients met Dispenzieri's diagnostic criteria, and those who completed at least four cycles of treatment from July 2013 to March 2021 were included. Results: The overall vascular endothelial growth factor (VEGF) response rate of this new treatment mode was 100%. The cumulative VEGF complete remission (CRV) rate was 67.9%, and the cumulative complete hematological response (CRH) rate was 55.6%. During the median 49-month follow-up, the 5-year-overall survival (OS) rate was 90.7%, the 3-year-progression-free survival (PFS) rate was 78.4%, and the 5-year-PFS rate was 73.8%. The BCD regimen achieved a 75% CRV rate (median time from diagnosis to CRV = 130 days) and 66.7% CRH rate (median time from diagnosis to CRH = 218 days). In addition, the VEGF response was less than the partial remission (PRV) after four-cycle induction treatment, which, together with a decrease on the Overall Neurological Limitation Scale of less than three points 1 year after consolidation treatment, was an independent poor prognostic factor. Conclusion: Bortezomib was well-tolerated by patients with POEMS syndrome. Compared with CD ± T regimen, BCD as the induction regimen achieved better VEGF response and earlier hematological remission. Autologous stem cell transplantation used as consolidation therapy further improved the neurological and hematological remission rates, resulting in better OS and PFS.

4.
Appl Opt ; 62(26): 6952-6960, 2023 Sep 10.
Article in English | MEDLINE | ID: mdl-37707034

ABSTRACT

Based on the liquid lens focus mechanism, a novel, to the best of our knowledge, optical tactile sensor is designed by taking advantage of the structure simplicity, fast response, and environmental immunity. The design of the tactile sensing mechanism used the liquid-membrane lens structure. To integrate the tactile sensing system, we designed a data acquisition circuit unit. A performance test platform was built, and performance testing and two application demonstrations were conducted. The experiment's result showed that the linear fitting degree was greater than 0.988, the load response time was 0.078 s, the target mass was accurately measured, the maximum error was less than 0.02 N, and the fine adjustment of the LED light intensity was achieved.

5.
Front Psychol ; 14: 1157209, 2023.
Article in English | MEDLINE | ID: mdl-37275727

ABSTRACT

Based on the limited resource model of self-control, we construct a chain mediation model to examine the relationship between parental phubbing and adolescents' academic burnout, and whether social anxiety and self-control play a mediating role in it. We used 4 questionnaires to investigate parental phubbing, social anxiety, self-control, and adolescents' academic burnout among 828 high school students in Wuhu and Huangshan City, Anhui Province, China. The findings indicated that: (1) parental phubbing, social anxiety, and self-control all significantly predict adolescents' academic burnout directly and (2) parental phubbing could indirectly influence adolescents' academic burnout through three pathways: the separate mediating effect of social anxiety and self-control, and the chain mediating effect on both. The results of this study help parents understand how their phubbing actions affect adolescents' academic burnout and the mechanism of action.

6.
Int J Mol Sci ; 24(12)2023 Jun 20.
Article in English | MEDLINE | ID: mdl-37373522

ABSTRACT

Ralstonia solanacearum, a pathogen causing widespread bacterial wilt disease in numerous crops, currently lacks an optimal control agent. Given the limitations of traditional chemical control methods, including the risk of engendering drug-resistant strains and environmental harm, there is a dire need for sustainable alternatives. One alternative is lysin proteins that selectively lyse bacteria without contributing to resistance development. This work explored the biocontrol potential of the LysP2110-HolP2110 system of Ralstonia solanacearum phage P2110. Bioinformatics analyses pinpointed this system as the primary phage-mediated host cell lysis mechanism. Our data suggest that LysP2110, a member of the Muraidase superfamily, requires HolP2110 for efficient bacterial lysis, presumably via translocation across the bacterial membrane. LysP2110 also exhibits broad-spectrum antibacterial activity in the presence of the outer membrane permeabilizer EDTA. Additionally, we identified HolP2110 as a distinct holin structure unique to the Ralstonia phages, underscoring its crucial role in controlling bacterial lysis through its effect on bacterial ATP levels. These findings provide valuable insights into the function of the LysP2110-HolP2110 lysis system and establish LysP2110 as a promising antimicrobial agent for biocontrol applications. This study underpins the potential of these findings in developing effective and environment-friendly biocontrol strategies against bacterial wilt and other crop diseases.


Subject(s)
Anti-Infective Agents , Bacteriophages , Ralstonia solanacearum , Ralstonia solanacearum/metabolism , Plant Diseases/prevention & control , Plant Diseases/microbiology , Anti-Bacterial Agents/pharmacology , Anti-Infective Agents/pharmacology
7.
JAMA Dermatol ; 159(7): 745-749, 2023 07 01.
Article in English | MEDLINE | ID: mdl-37195706

ABSTRACT

Importance: Grover disease (GD), a truncal eruption that typically occurs in older individuals, is exacerbated by sweating, irradiation, cancers, medications, kidney failure, and organ transplantation. The pathobiology of GD remains unknown. Objective: To determine if damaging somatic single-nucleotide variants (SNVs) are associated with GD. Design, Setting, and Participants: In this retrospective case series, we identified consecutive patients from a dermatopathology archive over a 4-year period (January 2007 to December 2011) who had 1 biopsy with a clinical diagnosis of GD confirmed via histopathologic findings and another non-GD biopsy. Participant DNA was extracted from both biopsy tissues and sequenced to high depth with a 51-gene panel to screen for SNVs in genes previously associated with acantholysis and Mendelian disorders of cornification. Analysis took place between 2021 and 2023. Main Outcomes and Measures: Comparative analysis of sequencing data from paired GD and control tissue was employed to identify SNVs predicted to affect gene function, which were exclusive to, or highly enriched in, GD tissue. Results: Overall, 12 of 15 cases of GD (12 men and 3 women; mean [SD] age, 68.3 [10.0] years) were associated with C>T or G>A ATP2A2 SNVs in GD tissue; all were predicted to be highly damaging via combined annotation dependent depletion (CADD) scores, and 4 were previously associated with Darier disease. In 9 cases (75%), the GD-associated ATP2A2 SNV was absent from control tissue DNA, and in 3 cases (25%), ATP2A2 SNVs were enriched 4- to 22-fold in GD vs control tissue. Conclusions and Relevance: In this case series study of 15 patients, damaging somatic ATP2A2 SNVs were associated with GD. This discovery expands the spectrum of acantholytic disorders associated with ATP2A2 SNVs and highlights the role of somatic variation in acquired disorders.


Subject(s)
Acantholysis , Ichthyosis , Sarcoplasmic Reticulum Calcium-Transporting ATPases , Aged , Female , Humans , Male , Acantholysis/genetics , Acantholysis/pathology , Darier Disease/genetics , Ichthyosis/diagnosis , Ichthyosis/genetics , Retrospective Studies
8.
Anticancer Drugs ; 34(3): 344-350, 2023 03 01.
Article in English | MEDLINE | ID: mdl-36622759

ABSTRACT

This study aimed to examine the effect of venetoclax coupled with azacytidine in treating older adults with relapsed and refractory (R/R) acute myeloid leukemia (AML). The clinical data of 10 senior patients with AML over 65 years old who were treated with venetoclax and azacytidine, including six patients with R/R AML, were retrospectively evaluated. This study comprised seven males and three females with a median age of 71 years. Five patients had at least one relapse, and one patient did not achieve remission after four cycles of azacytidine monotherapy, considering it resistant. AML with myelodysplasia-related changes was found in four cases. One of the 10 patients died early after 1-13 cycles of venetoclax plus azacytidine treatment due to a protracted period of neutropenia and severe lung infection induced by medications. Six of the remaining nine patients, including six R/R patients, achieved a complete remission (CR) or a CR with incomplete hematologic recovery (CRi). After two cycles of therapy, one patient did not react. Neutropenia lasted an average of 10.5 (6-15) days in all patients, with the most severe cases occurring in the second and third weeks of therapy. Three patients who tested positive for the TP53 gene mutation had the following outcomes: One relapsed patient has been in progression-free remission (PFS) for the past 24 months, whereas another has been in full remission but relapsed 2 months later. Another patient experienced complete remission in myelology for 4 months, but the variable allele fraction (VAF) value steadily rose, suggesting that the illness was on the verge of progressing. IDH2 gene alterations were found in three of four patients who obtained maintained CR for more than 18 months following recurrence. Venetoclax in combination with azacytidine is a successful and well-tolerated therapy for R/R AML in the elderly. Venetoclax and azacytidine may help patients with TP53 mutations and reduce VAF. The IDH2 mutation might be a good predictor of veneclax sensitivity. A notable adverse response in the treatment phase of the regimen is severe infection induced by neutropenia.


Subject(s)
Leukemia, Myeloid, Acute , Neutropenia , Male , Female , Humans , Aged , Azacitidine/adverse effects , Retrospective Studies , Leukemia, Myeloid, Acute/drug therapy , Bridged Bicyclo Compounds, Heterocyclic , Neutropenia/chemically induced , Antineoplastic Combined Chemotherapy Protocols/therapeutic use
9.
Inflamm Res ; 72(2): 347-362, 2023 Feb.
Article in English | MEDLINE | ID: mdl-36544058

ABSTRACT

OBJECTIVES: Excessive inflammatory responses and apoptosis are critical pathologies that contribute to sepsis-induced acute kidney injury (SI-AKI). Annexin A1 (ANXA1), a member of the calcium-dependent phospholipid-binding protein family, protects against SI-AKI through its anti-inflammatory and antiapoptotic effects, but the underlying mechanisms are still largely unknown. METHODS: In vivo, SI-AKI mouse models were established via caecal ligation and puncture (CLP) and were then treated with the Ac2-26 peptide of ANXA1 (ANXA1 (Ac2-26)), WRW4 (Fpr2 antagonist) or both. In vitro, HK-2 cells were induced by lipopolysaccharide (LPS) and then treated with ANXA1 (Ac2-26), Fpr2-siRNA or both. RESULTS: In the present study, we found that the expression levels of ANXA1 were decreased, and the expression levels of TNF-α, IL-1ß, IL-6, cleaved caspase-3, cleaved caspase-8 and Bax were significantly increased, accompanied by marked kidney tissue apoptosis in vivo. Moreover, we observed that ANXA1 (Ac2-26) significantly reduced the levels of TNF-α, IL-1ß and IL-6 and cleaved caspase-3, cleaved caspase-8, FADD and Bax and inhibited apoptosis in kidney tissue and HK-2 cells, accompanied by pathological damage to kidney tissue. Seven-day survival, kidney function and cell viability were significantly improved in vivo and in vitro, respectively. Furthermore, the administration of ANXA1 (Ac2-26) inhibited the CLP- or LPS-induced phosphorylation of PI3K and AKT and downregulated the level of NF-κB in vivo and in vitro. Moreover, our data demonstrate that blocking the Fpr2 receptor by the administration of WRW4 or Fpr2-siRNA reversed the abovementioned regulatory role of ANXA1, accompanied by enhanced phosphorylation of PI3K and AKT and upregulation of the level of NF-κB in vivo and in vitro. CONCLUSIONS: Taken together, this study provides evidence that the protective effect of ANXA1 (Ac2-26) on SI-AKI largely depends on the negative regulation of inflammation and apoptosis via the Fpr2 receptor.


Subject(s)
Acute Kidney Injury , Annexin A1 , Sepsis , Mice , Animals , NF-kappa B/metabolism , Caspase 3/metabolism , Caspase 8/metabolism , Caspase 8/pharmacology , Lipopolysaccharides/pharmacology , Tumor Necrosis Factor-alpha/metabolism , Interleukin-6/metabolism , Proto-Oncogene Proteins c-akt/metabolism , Annexin A1/pharmacology , Annexin A1/therapeutic use , Annexin A1/genetics , bcl-2-Associated X Protein/metabolism , bcl-2-Associated X Protein/pharmacology , Inflammation/drug therapy , Inflammation/metabolism , Acute Kidney Injury/drug therapy , Acute Kidney Injury/etiology , Acute Kidney Injury/metabolism , Apoptosis , Sepsis/complications , Sepsis/drug therapy , Sepsis/metabolism , RNA, Small Interfering/genetics , RNA, Small Interfering/pharmacology , Phosphatidylinositol 3-Kinases/metabolism
11.
Heliyon ; 8(12): e12201, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36578403

ABSTRACT

POEMS syndrome is a plasma cell disease. Clinical manifestations and clinical onset are variable. In recent years, more and more cases of POEMS syndrome with cerebrovascular disease and ischemic stroke have been reported. However, it is rare for patients with POEMS syndrome to present with a cerebrovascular accident as the first clinical manifestation. We presented three cases of POEMS syndrome with cerebral infarction in different phases of the disease. We then searched the literature for studies involving POEMS syndrome complicated with cerebral infarction. There were 81 cases in total. In nine patients, cerebral infarctions occurred before polyneuropathy. Patients with cerebral infarction before polyneuropathy have better prognosis of POEMS than those with cerebral infarction after polyneuropathy.

12.
Comput Intell Neurosci ; 2022: 1603104, 2022.
Article in English | MEDLINE | ID: mdl-36299440

ABSTRACT

A long calibration procedure limits the use in practice for a motor imagery (MI)-based brain-computer interface (BCI) system. To tackle this problem, we consider supervised and semisupervised transfer learning. However, it is a challenge for them to cope with high intersession/subject variability in the MI electroencephalographic (EEG) signals. Based on the framework of unsupervised manifold embedded knowledge transfer (MEKT), we propose a supervised MEKT algorithm (sMEKT) and a semisupervised MEKT algorithm (ssMEKT), respectively. sMEKT only has limited labelled samples from a target subject and abundant labelled samples from multiple source subjects. Compared to sMEKT, ssMEKT adds comparably more unlabelled samples from the target subject. After performing Riemannian alignment (RA) and tangent space mapping (TSM), both sMEKT and ssMEKT execute domain adaptation to shorten the differences among subjects. During domain adaptation, to make use of the available samples, two algorithms preserve the source domain discriminability, and ssMEKT preserves the geometric structure embedded in the labelled and unlabelled target domains. Moreover, to obtain a subject-specific classifier, sMEKT minimizes the joint probability distribution shift between the labelled target and source domains, whereas ssMEKT performs the joint probability distribution shift minimization between the unlabelled target domain and all labelled domains. Experimental results on two publicly available MI datasets demonstrate that our algorithms outperform the six competing algorithms, where the sizes of labelled and unlabelled target domains are variable. Especially for the target subjects with 10 labelled samples and 270/190 unlabelled samples, ssMEKT shows 5.27% and 2.69% increase in average accuracy on the two abovementioned datasets compared to the previous best semisupervised transfer learning algorithm (RA-regularized common spatial patterns-weighted adaptation regularization, RA-RCSP-wAR), respectively. Therefore, our algorithms can effectively reduce the need of labelled samples for the target subject, which is of importance for the MI-based BCI application.


Subject(s)
Brain-Computer Interfaces , Humans , Electroencephalography/methods , Imagery, Psychotherapy , Algorithms , Calibration , Imagination
14.
Article in English | MEDLINE | ID: mdl-35170712

ABSTRACT

The effect of antiretroviral therapy (ART) on CD4+/CD25hi/CD127low T lymphocyte changes in people living with HIV/AIDS (PLWHA) is still a matter of debate. From October 2015 to December 2019, peripheral blood from 70 cases of PLWHA were collected for the detection of CD4+/CD25hi/CD127low T lymphocytes by flow cytometry. Statistical analysis was performed to detect changes of CD4+/CD25hi/CD127low T lymphocytes in patients with different duration of ART and different treatment effects. We found that the number of CD4+/CD25hi/CD127low T lymphocytes in ART-naive PLWHA were lower than those in healthy volunteers (10.3±Ù¦.Ù  cells/uL vs 31.7±8.0 cells/uL, P < 0.05). CD4+/CD25hi/CD127low T lymphocyte counts increased to 17.8±Ù¤.Ù  cells/uL 6 months post-ART and 25.0±Ù¡Ù¡.Ù© cells/uL 9 months post-ART, respectively (P < 0.05). There was no significant difference in CD4+/CD25hi/CD127low T lymphocyte counts between PLWHA who reached a complete immune reconstruction after ART and healthy volunteers. The growth of CD4+/CD25hi/CD127low T lymphocyte counts in patients who had baseline CD4 > 200 cells/uL was greater than those who had baseline CD4 ≤ 200 cells/uL (12.6±Ù¤.Ù¦ cells/uL vs 5.6±Ù¥.Ù  cells/uL, P = 0.027). CD4+/CD25hi/CD127low T lymphocyte counts were positively correlated with CD4+ T lymphocyte counts (r = 0.923, P < 0.001) and CD4+/CD8+ ratio (r = 0.741, P < 0.001), but were negatively correlated with HIV-VL (r = -0.648, P = 0.000). In conclusion, the results of the present study showed that changes in CD4+/CD25hi/CD127low T lymphocyte counts can be used to assess the effect of ART in PLWHA.


Subject(s)
CD4-Positive T-Lymphocytes , HIV Infections , CD4 Lymphocyte Count , Flow Cytometry , HIV Infections/drug therapy , Humans
15.
Cureus ; 14(11): e32031, 2022 Nov.
Article in English | MEDLINE | ID: mdl-36600821

ABSTRACT

Retroperitoneal fibrosis (RF) is a rare disease, which can be primary (idiopathic) or secondary. We present the case of a 56-year-old patient with symptomatic RF, in whom, after ineffective treatment with glucocorticoids, immunosuppressants, and non-steroidal anti-inflammatory drugs for one year and a progressive clinical course, a follicular lymphoma in the retroperitoneal space and several lymphoma nodes was identified. We also include a literature review on differential diagnosis through image inspection and case reports of lymphoma mimicking RF.

16.
Article in English | LILACS-Express | LILACS | ID: biblio-1360791

ABSTRACT

ABSTRACT The effect of antiretroviral therapy (ART) on CD4+/CD25hi/CD127low T lymphocyte changes in people living with HIV/AIDS (PLWHA) is still a matter of debate. From October 2015 to December 2019, peripheral blood from 70 cases of PLWHA were collected for the detection of CD4+/CD25hi/CD127low T lymphocytes by flow cytometry. Statistical analysis was performed to detect changes of CD4+/CD25hi/CD127low T lymphocytes in patients with different duration of ART and different treatment effects. We found that the number of CD4+/CD25hi/CD127low T lymphocytes in ART-naive PLWHA were lower than those in healthy volunteers (10.3±٦.٠ cells/uL vs 31.7±8.0 cells/uL, P < 0.05). CD4+/CD25hi/CD127low T lymphocyte counts increased to 17.8±٤.٠ cells/uL 6 months post-ART and 25.0±١١.٩ cells/uL 9 months post-ART, respectively (P < 0.05). There was no significant difference in CD4+/CD25hi/CD127low T lymphocyte counts between PLWHA who reached a complete immune reconstruction after ART and healthy volunteers. The growth of CD4+/CD25hi/CD127low T lymphocyte counts in patients who had baseline CD4 > 200 cells/uL was greater than those who had baseline CD4 ≤ 200 cells/uL (12.6±٤.٦ cells/uL vs 5.6±٥.٠ cells/uL, P = 0.027). CD4+/CD25hi/CD127low T lymphocyte counts were positively correlated with CD4+ T lymphocyte counts (r = 0.923, P < 0.001) and CD4+/CD8+ ratio (r = 0.741, P < 0.001), but were negatively correlated with HIV-VL (r = −0.648, P = 0.000). In conclusion, the results of the present study showed that changes in CD4+/CD25hi/CD127low T lymphocyte counts can be used to assess the effect of ART in PLWHA.

17.
Biomed Res Int ; 2021: 5486131, 2021.
Article in English | MEDLINE | ID: mdl-34631884

ABSTRACT

Recent studies have found that cytoskeleton-associated protein 2 like (CKAP2L), an important oncogene, is involved in the biological behavior of many malignant tumors, but its function in the malignant course of glioma has not been confirmed. The main purpose of this study was to clarify the relationship between prognostic clinical characteristics of glioma patients and CKAP2L expression using data collected from the GEPIA, HPA, CGGA, TCGA, and GEO databases. CKAP2L expression was significantly increased in glioma. Further, Kaplan-Meier plots revealed that increased expression of CKAP2L was associated with shorter survival time of glioma patients in datasets retrieved from multiple databases. Cox regression analysis indicated that CKAP2L can serve as an independent risk factor but also has relatively reliable diagnostic value for the prognosis of glioma patients. The results of gene set enrichment analysis suggested that CKAP2L may play a regulatory role through the cell cycle, homologous recombination, and N-glycan biosynthesis cell signaling pathways. Several drugs with potential inhibitory effects on CKAP2L were identified in the CMap database that may have therapeutic effects on glioma. Finally, knockdown of CKAP2L inhibited the proliferation and invasion of cells by reducing the expression level of cell cycle-related proteins. This is the first study to demonstrate that high CKAP2L expression leads to poor prognosis in glioma patients, providing a novel target for diagnosis and treatment of glioma.


Subject(s)
Cytoskeletal Proteins/metabolism , Glioma/diagnosis , Glioma/metabolism , Antineoplastic Agents/chemistry , Antineoplastic Agents/pharmacology , Carcinogenesis/genetics , Carcinogenesis/pathology , Cell Line, Tumor , Cytoskeletal Proteins/genetics , Databases, Genetic , Gene Expression Regulation, Neoplastic , Humans , Neoplasm Grading , Prognosis , RNA, Messenger/genetics , RNA, Messenger/metabolism , Reproducibility of Results , Risk Factors , Signal Transduction , Survival Analysis
18.
Cell Death Discov ; 7(1): 297, 2021 Oct 18.
Article in English | MEDLINE | ID: mdl-34663800

ABSTRACT

DNA (cytosine-5)-methyltransferase 3A (DNMT3A) mutations occur in ~20% of de novo acute myeloid leukemia (AML) patients, and >50% of these mutations in AML samples are heterozygous missense alterations within the methyltransferase domain at residue R882. DNMT3A R882 mutations in AML patients promote resistance to anthracycline chemotherapy and drive relapse. In this study, we performed high-throughput screening and identified that oridonin, an ent-kaurene diterpenoid extracted from the Chinese herb Rabdosia rubescens, inhibits DNMT3A R882 mutant leukemic cells at a low-micromolar concentration (IC50 = 2.1 µM) by activating both RIPK1-Caspase-8-Caspase-3-mediated apoptosis and RIPK1-RIPK3-MLKL-mediated necroptosis. The inhibitory effect of oridonin against DNMT3A R882 mutant leukemia cells can also be observed in vivo. Furthermore, oridonin inhibits clonal hematopoiesis of hematopoietic stem cells (HSCs) with Dnmt3a R878H mutation comparing to normal HSCs by inducing apoptosis and necroptosis. Overall, oridonin is a potential and promising drug candidate or lead compound targeting DNMT3A R882 mutation-driven clonal hematopoiesis and leukemia.

19.
Front Neurosci ; 15: 733546, 2021.
Article in English | MEDLINE | ID: mdl-34489636

ABSTRACT

In an electroencephalogram- (EEG-) based brain-computer interface (BCI), a subject can directly communicate with an electronic device using his EEG signals in a safe and convenient way. However, the sensitivity to noise/artifact and the non-stationarity of EEG signals result in high inter-subject/session variability. Therefore, each subject usually spends long and tedious calibration time in building a subject-specific classifier. To solve this problem, we review existing signal processing approaches, including transfer learning (TL), semi-supervised learning (SSL), and a combination of TL and SSL. Cross-subject TL can transfer amounts of labeled samples from different source subjects for the target subject. Moreover, Cross-session/task/device TL can reduce the calibration time of the subject for the target session, task, or device by importing the labeled samples from the source sessions, tasks, or devices. SSL simultaneously utilizes the labeled and unlabeled samples from the target subject. The combination of TL and SSL can take advantage of each other. For each kind of signal processing approaches, we introduce their concepts and representative methods. The experimental results show that TL, SSL, and their combination can obtain good classification performance by effectively utilizing the samples available. In the end, we draw a conclusion and point to research directions in the future.

20.
World J Clin Cases ; 9(22): 6566-6574, 2021 Aug 06.
Article in English | MEDLINE | ID: mdl-34435027

ABSTRACT

BACKGROUND: Primary non-dural central nervous system mucosa-associated lymphoid tissue (MALT) lymphoma is a rare indolent B-cell lymphoma, with only a few reported cases worldwide. CASE SUMMARY: A 33-year-old man presented with a 5-mo history of left blepharoptosis and a 4-mo history of right limb numbness and weakness. Magnetic resonance imaging showed a significantly enhanced mass in the left midbrain. Subsequent positron emission tomography revealed that the lesion had increased glucose uptake. A stereotactic robotic biopsy supported a diagnosis of MALT lymphoma. Then he was treated with radiation therapy (30Gy/15F), which resulted in complete remission. We also review the literature on brain parenchymal-based MALT lymphoma, including the clinical presentation, treatment options, and outcomes. CONCLUSION: Although there is no consensus on the optimal treatment for this rare disease, patients can respond well when treated with radiotherapy alone.

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