CD20+ T cells: phenotype, origin and presence in the tumour microenvironment

CD20 is well-known as a lineage marker for B cells in human, although the presence of CD20+ T cells has been reported previously (Schuh et al., 2016). In my experiments we sorted memory CD8+CD20+ and CD20- T cells and subsequently analysed TCRβ CDR3 sequences to determine clonal overlap between populations. I was able to demonstrate TCRβ CDR3 amino acid sequences within the CD20+ T cells that were not found in the CD20- T cells population, suggesting the presence of unique T cell clones. This data suggests possible thymic origin of at least some CD20+ T cells, or an early expression of CD20+ following activation of naïve T cells. This does not however refute the trogocytosis theory where some T cells acquire CD20 from B cell. I analysed a number of published mass cytometry datasets and determined that memory CD20+ T cells express higher levels of CD127, CD27, CD28, PD-1 and CD57 especially by the effector memory (Tem) and effector memory CD45RA revertant (Temra) subsets, suggesting a possible late differentiation state of the CD20+ T cells. Further phenotyping revealed a novel population of CD20+Vα7.2+CD161+ cells in the peripheral blood of healthy donors, which are potentially CD20+ mucosal-invariant T (MAIT) cells. In colon cancer, CD20+ T cells were found within tumour tissue, adjacent normal tissue and showed fewer CD20+ T cells expressing the marker CD39. This may indicate lower numbers of CD20+ T cells within tumour-reactive T cell pool and requires further investigation. Using mass cytometry datasets from colorectal cancer patients, and melanoma patients receiving anti- programmed cells death (PD-1) or anti-cytotoxic T lymphocyte-associated protein-4 (CTLA-4), CD20+ T cells showed similar phenotypes to those found in healthy peripheral blood. Importantly, they produced higher levels of cytokines compared to the CD20- T cells including; TNF-α, IFN-γ, IL-2, IL-17, and MIP-1β. My data, including both primary data and analysis of published datasets, indicates that CD20+ T cells can originate as a separate lineage, in addition to acquiring CD20 by trogocytosis. CD20+ T cells were found to be more highly differentiated, with increased cytokine production and contained a high frequency of CD20+ Vα7.2+CD161+ cells. Although there was no detectable difference in cancer, future work will be required to determine if they play any role within the tumour microenvironment or other pathological scenarios

Synthesis and characterization of novel denosumab/magnesium-based metal organic frameworks nanocomposite prepared by ultrasonic route as drug delivery system for the treatment of osteoporosis

Introduction: The metal-organic frameworks (MOF) have shown fascinating possibilities in biomedical applications, and designing a drug delivery system (DDS) based on the MOF is important. This work aimed at developing a suitable DDS based on Denosumab-loaded Metal Organic Framework/Magnesium (DSB@MOF (Mg)) for attenuating osteoarthritis.Materials and Methods: The MOF (Mg) (Mg3(BPT)2(H2O)4) was synthesized using a sonochemical protocol. The efficiency of MOF (Mg) as a DDS was evaluated by loading and releasing DSB as a drug. In addition, the performance of MOF (Mg) was evaluated by releasing Mg ions for bone formation. The MOF (Mg) and DSB@MOF (Mg) cytotoxicity towards the MG63 cells were explored by MTT assay.Results: MOF (Mg) characterized by using XRD, SEM, EDX, TGA, and BET. Drug loading, and releasing experiments proved that DSB was loaded on the MOF (Mg) and approximately 72% DSB was released from it after 8 h. The characterization techniques showed that MOF (Mg) was successfully synthesized with good crystal structure and thermal stability. The result of BET showed that MOF (Mg) had high surface areas and pore volume. This is the reason why its 25.73% DSB was loaded in the subsequent drug-loading experiment. Drug release and ion release experiments indicated DSB@MOF (Mg) had a good controlled release of DSB and Mg ions in solution. Cytotoxicity assay confirmed that the optimum dose of it had excellent biocompatibility and could stimulate the proliferation of MG63 cells as time went on.Conclusion: Due to the high loading amount of DSB and releasing time, DSB@MOF (Mg) can be promising as a suitable candidate for relieving bone pain caused by osteoporosis, with ossification-reinforcing functions

Hydrogel assistant synthesis of new Ti-MOF cross-linked oxidized pectin and chitosan with anti-breast cancer properties

Breast cancer is one of the most common diseases of the modern age. Although many methods for its treatment have been reported so far, the report and synthesis of new compounds based on new technologies, especially nanotechnology, is important. One of the laboratory methods for evaluating the anticancer properties of compounds is the in vitro MTT method (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide). In this study, the in vitro anti-breast cancer activity of the newly synthesized (Titanium Metal-Organic Framework) Ti-MOF cross-linked oxidized pectin and chitosan hydrogel, which uses biopolymers in its synthesis and structure, was investigated. The anticancer activity results showed that the synthetic nanopolymer had cell proliferation and viability of 27% more than the control and (the half maximal inhibitory concentration) IC50 of 111 μg/mL against breast cancer cells. Before the anticancer evaluation, the structure of the synthesized Ti-MOF cross-linked oxidized pectin, and chitosan hydrogel was confirmed by (X-Ray Diffraction) XRD pattern (Fourier Transform Infrared) FT-IR spectrum (Energy-dispersive X-ray) EDAX spectroscopy, N2 adsorption/desorption isotherm and (Scanning Electron Microscope) Scanning Electron Microscope images. The results of identification and characterization showed that the synthetic nanopolymer was in the range of nanoparticles. The peaks of the expected functional groups and reactant elements were observed in the FT-IR spectrum and energy-dispersive X-ray spectroscopy of the final product. High physicochemical capabilities such as the uniform morphology, crystallization of particles, and high specific surface area from synthesized Ti-MOF cross-linked oxidized pectin, and chitosan hydrogel were observed. The unique properties of the synthesized Ti-MOF cross-linked oxidized pectin and chitosan hydrogel can be attributed to the appropriate method of its synthesis that was carried out in this study

Fibroblastic reticular cells provide a supportive niche for lymph node–resident macrophages

The lymph node (LN) is home to resident macrophage populations that are essential for immune function and homeostasis, but key factors controlling this niche are undefined. Here, we show that fibroblastic reticular cells (FRCs) are an essential component of the LN macrophage niche. Genetic ablation of FRCs caused rapid loss of macrophages and monocytes from LNs across two in vivo models. Macrophages co‐localized with FRCs in human LNs, and murine single‐cell RNA‐sequencing revealed that FRC subsets broadly expressed master macrophage regulator CSF1. Functional assays containing purified FRCs and monocytes showed that CSF1R signaling was sufficient to support macrophage development. These effects were conserved between mouse and human systems. These data indicate an important role for FRCs in maintaining the LN parenchymal macrophage niche

Synthesis of novel Fe3O4 nanostructures surrounded by Ti-MOF nanostructures as bioactive and efficient catalysts in three-component synthesis of new pyrazole derivatives

Synthesis and reporting of new nanoparticles with diverse properties is important in chemistry. A one-step, rapid and controllable synthesis of the new Fe3O4 surrounded in Ti-MOF nanostructures was carried out with microwave technology. After identifying and confirming the structure, Fe3O4 surrounded in Ti-MOF nanostructures was used as a suitable catalyst with high thermal resistance and recyclable in a three-component reaction of phenylhydrazine, malononitrile and aldehyde to synthesis novel pyrazole derivatives. Continuing investigations on Fe3O4 surrounded in Ti-MOF nanostructures, its antimicrobial properties were tested on Gram-positive bacterial species, Gram-negative bacterial species and fungi bacterial. Identification of Fe3O4 surrounded in Ti-MOF nanostructures with morphology and size distribution technique (SEM), surface area technique (BET), Infrared spectroscopy (FT-IR), Energy-Dispersive X-ray spectroscopy (EDX/EDX mapping), and Vibrating Sample Magnetometer (VSM) were performed. Synthesized pyrazole derivatives with Fe3O4 surrounded in Ti-MOF nanostructures than previously reported methods have less synthesis time and high efficiency. In antimicrobial properties high effects were observed based on MIC, MBC, and MFC values

Advanced adsorptions of non-steroidal anti-inflammatory drugs from environmental waters in improving offline and online preconcentration techniques : An analytical review

Humans and animals frequently utilize nonsteroidal anti-inflammatory drugs (NSAIDs) as analgesics for various conditions. The ubiquitous use of NSAIDs has resulted in their widespread presence in environmental waters (concentrations detected in water (Malaysia) ranging from 1.40 × 10-1 to 9.72 × 10-2 mg L−1), which may threaten human health. Consequentially, continuous vigilance and resolve are indispensable for preventing any catastrophe. Numerous preconcentration techniques have been developed in response to the rising demand for a rapid, sensitive, and robust method capable of producing a dependable result (relative recoveries (RR) > 70% and limit of detection (LOD) 0.1 ng mL−1). Methods: This review aims to summarize the advancement of pre-concentration techniques using advanced adsorptive materials in quantifying NSAIDs from water mediums. Different univariate and multivariate optimization approaches for offline and online preconcentration are discussed in detail. Significant findings: The multivariate approach is more promising compared to conventional approach for developing an offline preconcentration technique. The analytical performance of online and offline preconcentration is comparable, but online preconcentration utilizes less solvent, aligning with the Green Analytical Chemistry initiative

Efficacy of tranexamic acid administration in traumatic brain injury patients: A review

BackgroundAnti-fibrinolytic medications decrease traumatic intracranial haemorrhage (ICH). Tranexamic acid (TXA) is an anti-fibrinolytic, which recently has shown effectiveness in management of traumatic haemorrhage‎.AimsTo summarize the randomized control trials (RCTs) that evaluate the efficacy of tranexamic acid administration in traumatic brain ‎injury (TBI) patients‎.‎Methods An electronic literature review, including PubMed, Google Scholar, and EBSCO that examining RCTs, observational, and experimental studies which study the efficacy of TXA administration in (TBI) patients.ResultsThe current review included 7 randomized studies reported the efficacy of TXA in management of TBI. TXA limit secondary brain injury by preventing the expansion of ICH. Administration of TXA exhibited a tendency to decrease head trauma-related mortality.ConclusionTXA significantly lower the risk of ICU expansion m and prevent brain injury related deaths

Mortality from gastrointestinal congenital anomalies at 264 hospitals in 74 low-income, middle-income, and high-income countries: a multicentre, international, prospective cohort study

Summary Background Congenital anomalies are the fifth leading cause of mortality in children younger than 5 years globally. Many gastrointestinal congenital anomalies are fatal without timely access to neonatal surgical care, but few studies have been done on these conditions in low-income and middle-income countries (LMICs). We compared outcomes of the seven most common gastrointestinal congenital anomalies in low-income, middle-income, and high-income countries globally, and identified factors associated with mortality. Methods We did a multicentre, international prospective cohort study of patients younger than 16 years, presenting to hospital for the first time with oesophageal atresia, congenital diaphragmatic hernia, intestinal atresia, gastroschisis, exomphalos, anorectal malformation, and Hirschsprung’s disease. Recruitment was of consecutive patients for a minimum of 1 month between October, 2018, and April, 2019. We collected data on patient demographics, clinical status, interventions, and outcomes using the REDCap platform. Patients were followed up for 30 days after primary intervention, or 30 days after admission if they did not receive an intervention. The primary outcome was all-cause, in-hospital mortality for all conditions combined and each condition individually, stratified by country income status. We did a complete case analysis. Findings We included 3849 patients with 3975 study conditions (560 with oesophageal atresia, 448 with congenital diaphragmatic hernia, 681 with intestinal atresia, 453 with gastroschisis, 325 with exomphalos, 991 with anorectal malformation, and 517 with Hirschsprung’s disease) from 264 hospitals (89 in high-income countries, 166 in middleincome countries, and nine in low-income countries) in 74 countries. Of the 3849 patients, 2231 (58·0%) were male. Median gestational age at birth was 38 weeks (IQR 36–39) and median bodyweight at presentation was 2·8 kg (2·3–3·3). Mortality among all patients was 37 (39·8%) of 93 in low-income countries, 583 (20·4%) of 2860 in middle-income countries, and 50 (5·6%) of 896 in high-income countries (p<0·0001 between all country income groups). Gastroschisis had the greatest difference in mortality between country income strata (nine [90·0%] of ten in lowincome countries, 97 [31·9%] of 304 in middle-income countries, and two [1·4%] of 139 in high-income countries; p≤0·0001 between all country income groups). Factors significantly associated with higher mortality for all patients combined included country income status (low-income vs high-income countries, risk ratio 2·78 [95% CI 1·88–4·11], p<0·0001; middle-income vs high-income countries, 2·11 [1·59–2·79], p<0·0001), sepsis at presentation (1·20 [1·04–1·40], p=0·016), higher American Society of Anesthesiologists (ASA) score at primary intervention (ASA 4–5 vs ASA 1–2, 1·82 [1·40–2·35], p<0·0001; ASA 3 vs ASA 1–2, 1·58, [1·30–1·92], p<0·0001]), surgical safety checklist not used (1·39 [1·02–1·90], p=0·035), and ventilation or parenteral nutrition unavailable when needed (ventilation 1·96, [1·41–2·71], p=0·0001; parenteral nutrition 1·35, [1·05–1·74], p=0·018). Administration of parenteral nutrition (0·61, [0·47–0·79], p=0·0002) and use of a peripherally inserted central catheter (0·65 [0·50–0·86], p=0·0024) or percutaneous central line (0·69 [0·48–1·00], p=0·049) were associated with lower mortality. Interpretation Unacceptable differences in mortality exist for gastrointestinal congenital anomalies between lowincome, middle-income, and high-income countries. Improving access to quality neonatal surgical care in LMICs will be vital to achieve Sustainable Development Goal 3.2 of ending preventable deaths in neonates and children younger than 5 years by 2030

Identification of ZINC08101049 as a potential IL1β inhibitor through molecular docking and MD simulations for cancer therapeutics

Cancer is a significant global health concern that has a major impact on morbidity and mortality worldwide. Research has demonstrated the involvement of Interleukin-1 beta (IL1β) in various aspects of cancer development and progression, including angiogenesis, tumor growth and metastasis. Consequently, targeting IL1β activity represents a promising approach for cancer therapeutics. In this study, we utilized molecular docking and MD simulations to discover potent IL1β inhibitors for the treatment of cancer. Five thousand compounds from ZINC15 database were screened against IL1β target, and the top ten small molecules were selected based on their binding energy. The small molecule named ‘ZINC08101049’ was prioritized based on binding energy (−9.1 kcal/Mol) and residual interaction specifically forming seven hydrogen bonds with amino acid residues namely GLN81, GLY136, LEU134, LYS138, SER84, THR137 and TYR24 of IL1β. Next, IL1β alone and in complex with ZINC08101049 was subjected to MD simulations to determine their behavior at atomic level. The results of molecular docking and MD simulation revealed ZINC08101049 as a potential inhibitor of IL1β, reflecting that ZINC08101049 can emerge as a promising small molecule paving for cancer therapeutics. Communicated by Ramaswamy H. Sarma</p