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Summary: Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease. Cellular and systemic lipid metabolism plays a significant role in the regulation of immune cell activities. However, the role of lipoprotein lipids and apolipoproteins in ITP remains elusive. The automatic biochemistry analyser was used to measure the levels of serum total cholesterol (TC), triglyceride (TG), low‐density lipoprotein cholesterol (LDL‐C), high‐density lipoprotein cholesterol (HDL‐C), apolipoprotein A‐I (apoA‐I), apoB, apoE and lipoprotein a [LP(a)]. Genetic variants strongly associated with circulating lipoprotein lipids and apolipoproteins (LDL‐C, apoB, TG, HDL‐C and apoA‐I) were extracted to perform Mendelian randomization (MR) analyses. Finally, drug‐target MR and passive ITP mice model was used to investigate the potential druggable targets of ITP. Levels of HDL‐C, apoA‐I, decreased and LP(a) increased in ITP patients compared with healthy controls. Low HDL‐C was causally associated with ITP susceptibility. Through drug‐target MR and animal modelling, ABCA1 was identified as a potential target to design drugs for ITP. Our study found that lipid metabolism is related to ITP. The causative association between HDL‐C and the risk of ITP was also established. The study provided new evidence of the aetiology of ITP. ABCA1 might be a potential drug target for ITP. [ABSTRACT FROM AUTHOR]

Background: The first‐line therapy is effective for the treatment of primary immune thrombocytopenia (ITP); however, maintaining the long‐term responses remains challenging. Low‐dose decitabine (DAC) has been adopted to treat refractory ITP, while its role in macrophage polarization has not been fully understood. We aimed to investigate the mechanistic role of DAC in M2 macrophage polarization and evaluated its therapeutic effect in ITP. Methods: The M2 monocytes were identified by flow cytometry from peripheral blood mononuclear cells in healthy controls (HCs) and ITP patients. The expression of PPARγ, Arg‐1, DNMT3b and NLRP3, together with IL‐10 plasma levels was measured to examine its function. Bisulfite‐sequencing PCR was used to evaluate the methylation status of PPARγ promoter, and the binding affinity of KLF4 was measured by Cut&Tag. A sh‐PPARγ THP‐1 cell line was created to verify if low‐dose DAC‐modulated M2 macrophage polarization was PPARγ‐dependent. The passive ITP models were used to investigate the therapeutic effects of low‐dose DAC and its role in modulating polarization and immunomodulatory function of macrophages. NLRP3 inflammasome and reactive oxygen species were also tested to understand the downstream of PPARγ. Results: The M2 monocytes with impaired immunoregulation were observed in ITP. After high‐dose dexamethasone (HD‐DXM) treatment, M2 monocytes increased significantly with the elevated expression of PPARγ, Arg‐1 and IL‐10 in CR patients. Low‐dose DAC promoted M2 macrophage polarization in a PPARγ‐dependent way via demethylating the promoter of PPARγ, especially the KLF4 binding sites. Low‐dose DAC alleviated ITP mice by restoring the M1/M2 balance and fine‐tuning immunomodulatory function of macrophages. The downstream of the PPARγ modulation of M2 macrophage polarization might physiologically antagonize NLRP3 inflammasome. Conclusions: Low‐dose DAC promoted M2 macrophage polarization due to the demethylation within the promoter of PPARγ, thus enhanced the KLF4 binding affinity in ITP. [ABSTRACT FROM AUTHOR]

OPLS-DA score plots were used for the pairwise difference polar metabolites analysis among adult CRC, senior CRC and HC groups. The expression of 5-aminovaleric acid and d-allose in adult CRC patients was higher than that of HC and senior CRC patients (Figure 1J,L). Blood samples from CRC patients and healthy control (HC) groups were collected and identified by LC-MS and GC-MS and used for trans-omics analysis (A). Dear Editor, Colorectal cancer (CRC) is third most frequently diagnosed malignancy with the second highest mortality rate among all cancers.[[1], [3]] As CRC survival is highly dependent upon early diagnosis and treatment, novel sensitive and non-invasive detective approaches f are urgently required.[5] CRC is characterized by metabolic reprogramming.[[6]] In present study, using plasma metabolome analysis, a large scale trans-omic network was constructed by connecting polar metabolite data, lipid data, clinical phenoms and survival outcomes of CRC patients. [Extracted from the article]

Summary: Primary immune thrombocytopenia (ITP) is an autoimmune disorder characterized by isolated thrombocytopenia. This bibliometric analysis was applied to identify the characteristics of global scientific output, the hotspots, and frontiers of ITP over the past 10 years. We retrieved publications from 2011 to 2021 from the Web of Science Core Collection (WoSCC). Bibliometrix package, VOSviewer, and Citespace were used to analyse and visualize the trend, distribution, and hotspots of research on ITP. Altogether, there were 2084 papers, written by 9080 authors from 410 organizations in 70 countries/regions, published in 456 journals with 37 160 co‐cited references. In the last decades, the most productive journal was British Journal of Haematology, China was the most productive country. and the most cited journal was Blood. Shandong University was the most productive institution in the field of ITP. NEUNERT C, 2011, BLOOD, CHENG G, 2011, LANCET, and PATEL VL, 2012, BLOOD were the top three most cited documents. "Thrombopoietin receptor agonist", "regulatory T cell" and "sialic acid" were three hotspots of the last decade. And "immature platelet fraction", "Th17", and "fostamatinib" would be research frontiers in the feature. The present study provided a novel insight for future research directions and scientific decision‐making. [ABSTRACT FROM AUTHOR]

Primary immune thrombocytopenia (ITP) is an acquired autoimmune disease with multiple immune cells take part in the pathogenesis. Macrophages play multiple roles in both innate and adaptive immune system. The report by Jiani Mo and colleagues identified new biomarkers and explore the role of mitophagy and ferroptosis in ITP pathogenesis. Commentary on: Mo et al. Comprehensive analysis and prediction model of mitophagy and ferroptosis in primary immune thrombocytopenia. Br J Haematol 2024;204:2429‐2442. [ABSTRACT FROM AUTHOR]

Objectives: Immune thrombocytopenia (ITP) is an autoimmune disease characterised by impaired platelet production and increased platelet destruction. However, the involvement of neutrophils in ITP is yet to be explored. Methods: B‐cell activating factor (BAFF) expression and activation markers of neutrophils, as well as activation of platelets in ITP patients and healthy controls were measured. The interaction of CD62P on platelets and BAFF in neutrophils was analysed by correlation analysis and verified by co‐culture. The effects of neutrophils on apoptosis of acquired immune cells were evaluated in co‐culture systems with or without belimumab. Results: The BAFF expression and activation of neutrophils were increased in active ITP patients. BAFF levels in neutrophils were positively correlated with CD62P+ platelets and neutrophils produced increased BAFF by interfering with CD62P on platelets. Neutrophils inhibited the apoptosis of CD4+, CD8+ and CD19+ cells dependent on BAFF levels, and belimumab could interrupt the effects of neutrophils. Conclusions: Neutrophils were overactivated in ITP patients and participated in the progression of disease by producing excessive BAFF, which could be regulated by CD62P on platelets. Targeting BAFF by belimumab may be a novel potential therapy for ITP. [ABSTRACT FROM AUTHOR]

Background: During pregnancy, mother–child interactions trigger a variety of subtle changes in the maternal body, which may be reflected in the status of peripheral blood mononuclear cells (PBMCs). Although these cells are easy to access and monitor, a PBMC atlas for pregnant women has not yet been constructed. Methods: We applied single‐cell RNA sequencing (scRNA‐seq) to profile 198,356 PBMCs derived from 136 pregnant women (gestation weeks 6 to 40) and a control cohort. We also used scRNA‐seq data to establish a transcriptomic clock and thereby predicted the gestational age of normal pregnancy. Results: We identified reconfiguration of the peripheral immune cell phenotype during pregnancy, including interferon‐stimulated gene upregulation, activation of RNA splicing‐related pathways and immune activity of cell subpopulations. We also developed a cell‐type‐specific model to predict gestational age of normal pregnancy. Conclusions: We constructed a single‐cell atlas of PBMCs in pregnant women spanning the entire gestation period, which should help improve our understanding of PBMC composition turnover in pregnant women. [ABSTRACT FROM AUTHOR]

Spatial transcriptomics is considered as an important part of spatiotemporal molecular images to bridge molecular information with clinical images. Of those potentials and opportunities, the excellent quality of human sample preparation and handling will ensure the precise and reliable information generated from clinical spatial transcriptome. The present study aims at defining potential factors that might influence the quality of spatial transcriptomics in lung cancer, para‐cancer, or normal tissues, pathological images of sections and the RNA integrity before spatial transcriptome sequencing. We categorised potential influencing factors from clinical aspects, including patient selection, pathological definition, surgical types, sample harvest, temporary preservation conditions and solutions, frozen approaches, transport and storage conditions and duration. We emphasis on the relationship between the combination of histological scores with RNA integrity number (RIN) and the unique molecular identifier (UMI), which is determines the quality of of spatial transcriptomics; however, we did not find significantly relevance between them. Our results showed that isolated times and dry conditions of sample are critical for the UMI and the quality of spatial transcriptomic samples. Thus, clinical procedures of sample preparation should be furthermore optimised and standardised as new standards of operation performance for clinical spatial transcriptome. Our data suggested that the temporary preservation time and condition of samples at operation room should be within 30 min and in 'dry' status. The direct cryo‐preservation within OCT media for human lung sample is recommended. Thus, we believe that clinical spatial transcriptome will be a decisive approach and bridge in the development of spatiotemporal molecular images and provide new insights for understanding molecular mechanisms of diseases at multi‐orientations. [ABSTRACT FROM AUTHOR]

Summary: Current first‐line treatments for immune thrombocytopenia (ITP) usually have transient effects and sustained platelet response off therapy remains low. We evaluated whether eltrombopag plus pulsed dexamethasone as first‐line therapy can increase the proportion of patients maintaining platelet counts >50 × 109/l for a prolonged period without further ITP therapy. Treatment consisted of eltrombopag 25–75 mg daily according to platelet response for 12 weeks plus dexamethasone, 40 mg daily for four consecutive days every four weeks for 1–3 courses. Primary endpoint was durable response off therapy defined as maintaining platelet counts >50 × 109/l for more than six months without further ITP therapy. Fifty ITP subjects were enrolled between November 2014 and March 2019. Out of 46 evaluable subjects, 26 (56·5%) had achieved the primary endpoint. The median platelet counts at six months off‐treatment follow‐up were 158 × 109/l. Only two out of 26 responders had relapsed at eight‐ and nine‐month follow‐up. The remaining 24 are still maintaining platelet counts >50 × 109/l, the longest over three years. All subjects tolerated treatment well and no Grade 3 or above adverse effects were reported. Eltrombopag plus pulsed dexamethasone as a first‐line therapy could result in durable response off therapy in a significant number of ITP subjects. [ABSTRACT FROM AUTHOR]

The application of precision medicine concept in clinical work needs a period of practice and experience accumulation. The present article introduced an example of functioning approach named "multidisciplinary therapy strategy of precision medicine" (MDTS‐PM), clinical practice and process, decision‐making, and therapies. The MDTS‐PM integrates multidisciplinary experts and develops real‐time therapeutic strategy based on clinical phenomes and gene sequencing of tissue DNA and circulating DNA. The strength of MDTS‐PM is the combination of dynamical clinical phenomes, genetic information, diagnosis, and treatment to make the therapy more targeted and specific. MDTS‐PM provides comprehensive, whole‐process, and personalized diagnosis and treatment services for patients with complex cancer or complex drug resistance progression; provides guidance for further adjustment of drug use; and establishes a multidisciplinary cooperative team, improves the quality of clinical diagnosis and treatment, and optimizes the process of medical services. [ABSTRACT FROM AUTHOR]

The condensation reaction between 6‐hydroxy‐2‐cyanobenzothiazole (CBT) and cysteine has been shown for various applications such as site‐specific protein labelling and in vivo cancer imaging. This report further expands the substrate scope of this reaction by varying the substituents on aromatic nitriles and amino thiols and testing their reactivity and ability to form nanoparticles for cell imaging. The structure–activity relationship study leads to the identification of the minimum structural requirement for the macrocyclization and assembly process in forming nanoparticles. One of the scaffolds made of 2‐pyrimidinecarbonitrile and cysteine joined by a benzyl linker was applied to design fluorescent probes for imaging caspase‐3/7 and β‐galactosidase activity in live cells. These results demonstrate the generality of this system for imaging hydrolytic enzymes. [ABSTRACT FROM AUTHOR]

Clinical and translational medicine is an ongoing opportunity and challenge to transition science from bench to patient, from patient to bench, and from patient to policy for scientists and clinicians. Of the many objectives, the most important one is to improve the quality of life in patients, including living duration, dignity, emotional well‐being, psychiatric and physical health, as well as independency. Emphasis and redefining concepts has allowed clinical and translational medicine to experience exciting and productive developments. Further discoveries, innovations, validations, and developments in clinical and translational medicine are expected in 2020. The present editorial aims to present the top three most discussed topics with high expectations for translation from clinical investigations and trials into practice and application. [ABSTRACT FROM AUTHOR]

Abstract: In the era of intensity modulation radiation therapy (IMRT), no prospective randomized trial has evaluated the efficacy of adjuvant therapies such as adjuvant concurrent chemoradiotherapy (CCRT), adjuvant sequential chemotherapy and radiotherapy (CT‐RT), and adjuvant CT alone in resectable pancreatic adenocarcinoma (PA). Through propensity score matching, we designed a nationwide, population‐based, head‐to‐head cohort study to determine the effects of dissimilar adjuvant treatments on resectable PA. We minimized the confounding of various adjuvant treatment outcomes among the following resectable PA groups of patients from the Taiwan Cancer Registry database: group 1, adjuvant CCRT; group 2, adjuvant sequential CT‐RT; and group 3, adjuvant CT alone. All the studied techniques are IMRTs. The matching process yielded a final cohort of 588 patients (196, 196, and 196 patients in groups 1, 2, and 3, respectively). In both univariate and multivariate Cox regression analyses, adjusted hazard ratios (aHRs; 95% confidence interval [CI]) of death derived for the adjuvant CCRT and adjuvant sequential CT‐RT cohorts compared with the adjuvant CT alone cohort were 0.398 (0.314–0.504) and 0.307 (0.235–0.402), respectively. A combination of adjuvant IMRT and CT for resectable PA treatment improves survival to a greater extent than does adjuvant CT alone. [ABSTRACT FROM AUTHOR]

Tuberculosis is a pulmonary disease with an especially high mortality rate in immuno-compromised populations, specifically children and HIV positive individuals. The causative agent, Mycobacterium tuberculosis ( Mtb), is a very slow growing and difficult organism to work with, making both diagnosis and development of effective treatments cumbersome. We utilize a fiber-optic fluorescence microendoscope integrated with a whole-body imaging system for in vivo Mtb detection. The system exploits an endogenous enzyme of Mtb ( β-lactamase, or BlaC) using a BlaC-specific NIR fluorogenic substrate. In the presence of BlaC, this substrate is cleaved and becomes fluorescent. Using intravital illumination of the lung to excite this probe, sensitivity of the optical system increases over trans- and epi-illumination methods of whole-body fluorescence imaging. We demonstrate that integration of these imaging technologies with BlaC-specific fluorescent reporter probe improves the level of detection to ∼100 colony forming units, a 100× increase in sensitivity in comparison to epi-illumination and a 10× increase in sensitivity in comparison to previous work in intravital excitation of tdTomato-expressing Mtb. This lower detection threshold enables the study of early stage bacterial infections with clinical strains of Mtb and longitudinal studies of disease pathogenesis and therapeutic efficacy with multiple time points in a single animal. [ABSTRACT FROM AUTHOR]

It is known that a disease is rarely a consequence of an abnormality of a single gene, but reflects the interactions of various processes in a complex network. Annotated molecular networks offer new opportunities to understand diseases within a systems biology framework and provide an excellent substrate for network-based identification of biomarkers. The network biomarkers and dynamic network biomarkers ( DNBs) represent new types of biomarkers with protein-protein or gene-gene interactions that can be monitored and evaluated at different stages and time-points during development of disease. Clinical bioinformatics as a new way to combine clinical measurements and signs with human tissue-generated bioinformatics is crucial to translate biomarkers into clinical application, validate the disease specificity, and understand the role of biomarkers in clinical settings. In this article, the recent advances and developments on network biomarkers and DNBs are comprehensively reviewed. How network biomarkers help a better understanding of molecular mechanism of diseases, the advantages and constraints of network biomarkers for clinical application, clinical bioinformatics as a bridge to the development of diseases-specific, stage-specific, severity-specific and therapy predictive biomarkers, and the potentials of network biomarkers are also discussed. [ABSTRACT FROM AUTHOR]

Current methods for the detection of Mycobacterium tuberculosis (Mtb) are either time consuming or require expensive instruments and are thus are not suitable for point-of-care diagnosis. The design, synthesis, and evaluation of fluorogenic probes with high specificity for BlaC, a biomarker expressed by Mtb, are described. The fluorogenic probe CDG-3 is based on cephalosporin with substitutions at the 2 and 7 positions and it demonstrates over 120 000-fold selectivity for BlaC over TEM-1 Bla, the most common β-lactamase. CDG-3 can detect 10 colony-forming units of the attenuated Mycobacterium bovis strain BCG in human sputum in the presence of high levels of contaminating β-lactamases expressed by other clinically prevalent bacterial strains. In a trial with 50 clinical samples, CDG-3 detected tuberculosis with 90 % sensitivity and 73 % specificity relative to Mtb culture within one hour, thus demonstrating its potential as a low-cost point-of-care test for use in resource-limited areas. [ABSTRACT FROM AUTHOR]

Reported herein is the design of fluorogenic probes specific for carbapenem-resistant Enterobacteriaceae (CRE) and they were designed based on stereochemically modified cephalosporin having a 6,7-trans configuration. Through experiments using recombinant β-lactamase enzymes and live bacterial species, these probes demonstrate the potential for use in the specific detection of carbapenemases, including metallo-βlactamases in active bacterial pathogens. [ABSTRACT FROM AUTHOR]

Background & Aims Thrombocytopaenia is a frequent feature in patients with HBV-related liver disease. Its underlying mechanism is not fully understood. Multiple factors might contribute to the development of thrombocytopaenia. In this study, we investigated the reticulated platelets ( RP), glycocalicin ( GC), serum thrombopoietin ( TPO) and platelet glycoprotein ( GP) in different stages of the disease. Methods One hundred and fourteen patients with HBV-related liver disease (30 with chronic hepatitis B ( CHB), 20 patients in Child A without thrombocytopaenia, 19 patients in Child A with thrombocytopaenia, 45 in Child B/C with thrombocytopaenia) and 25 normal controls ( NC) were enrolled. Liver cirrhosis ( LC) was classified according to modified Child-Turcotte-Pugh ( CTP) score. Serum TPO levels and GC were measured by ELISA. RP and platelet glycoprotein ( GP) expression were detected by flow cytometry. Results The TPO levels of patients with LC were significantly lower than that of controls, even in patients of Child A without thrombocytopaenia group. Serum TPO level was positively correlated ( r = 0.65, p < 0.01) with serum albumin in Child B/C group. Both the RP percentages and the glycocalicin index ( GCI) levels were significantly higher in patients groups including CHB and Child A without thrombocytopaenia than that of normal controls. A negative correlation existed in HBV DNA copies and the GPs% in patients with CHB and Child A without thrombocytopaenia. Conclusion Abnormal platelet production, destruction and platelet-specific glycoproteins levels were detected before the occurrence of thrombocytopaenia in HBV-related liver disease, indicating that multiple mechanisms might play roles in thrombocytopaenia in HBV-infected patients. [ABSTRACT FROM AUTHOR]

Post-synthesis modification of DNA is an important way of functionalizing DNA molecules. Herein, we describe a method that first enzymatically incorporates a cyanobenzothiazole (CBT)-modified thymidine. The side-chain handle CBT can undergo a rapid and site-specific cyclization reaction with 1,2-aminothiols to afford DNA functionalization in aqueous solution. Another key advantage of this method is the formation of a single stereo/regioisomer in the process, which allows for precise control of DNA modification to yield a single component for aptamer selection work and other applications. [ABSTRACT FROM AUTHOR]

Carbohydrates are known to mediate a large number of biological and pathological events. Small and macromolecules capable of carbohydrate recognition have great potentials as research tools, diagnostics, vectors for targeted delivery of therapeutic and imaging agents, and therapeutic agents. However, this potential is far from being realized. One key issue is the difficulty in the development of 'binders' capable of specific recognition of carbohydrates of biological relevance. This review discusses systematically the general approaches that are available in developing carbohydrate sensors and 'binders/receptors,' and their applications. The focus is on discoveries during the last 5 years. © 2009 Wiley Periodicals, Inc. Med Res Rev, 30, No. 2, 171-257, 2010 [ABSTRACT FROM AUTHOR]

Review: 22 refs. [ABSTRACT FROM AUTHOR]