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How to Use a Prioritised Approach for Treating Hematological Disorders During the COVID-19 Pandemic in India?

The current pandemic coronavirus, SARS-CoV-2, is known to cause severe infection (COVID-19) in patients with comorbidities, particularly cancer or an immunosuppressed state. Most healthcare systems in the country are likely to be overwhelmed soon if the pandemic moves to a stage of community transmission. Currently, limited evidence is available for managing patients with hematological disorders during the COVID-19 pandemic. The current review summarises the possible challenges clinicians are likely to face, key considerations to guide decision making, and possible solutions to the anticipated

Mucosal-Associated Invariant T Cells in Health and Disease.

Mucosal-associated invariant T (MAIT) cells are a population of evolutionarily conserved, unconventional innate-like T lymphocytes that are restricted by major histocompatibility complex Class I-related (MR1) molecules. They can be activated either in a T-cell receptor-MR1- or cytokine-dependent manner. Activated MAIT cells play crucial roles in maintaining homeostasis and the fine regulation of the immune system. This review presents a systematic exploration of the development, biological characteristics, and multiple effects of MAIT cells in health and various diseases. In healthy individual

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… In humans, the earliest cells (Stage 1) are defined as CD3 + and MR1 tetramer‐positive (MR1‐tet + ), lacking the expression of the surface markers CD27 and CD161 and are predominantly CD4 + CD8 + or CD4 + CD8 − thymocytes. … Developing MAIT cells in Stage 2 express CD27 but not CD161 and are mostly CD4 + CD8 − or CD4 + CD8 + thymocytes, with a small percentage migrate to the periphery. …

Cytokine-induced killer cells: new insights for therapy of hematologic malignancies.

BackgroundCytokine-induced killer (CIK) cells are a novel subgroup of immune effectors, classified as one of the modified T cell-mediated arms for immunotherapy. These cells exert MHC-unrestricted cytotoxicity against both hematological and solid malignancies with low incidence of treatment-related severe complications. This study reviews the application of CIK cells in treating cases with hematologic malignancies.Main bodyCIK cells consist of CD3+/CD56+ natural killer (NK) T cells, CD3-/CD56+ NK cells, and CD3+/CD56- cytotoxic T cells. In this regard, the CD3+/CD56+ NK T cells are the primary

Changes in C-Reactive Protein Forecast Infection Risk Following Treatment with Chimeric Antigen Receptor T Cells.

BACKGROUND: Immunosuppressive conditioning regimens for chimeric antigen receptor-modified T cell immunotherapy (CARTx) and subsequent T cell dysfunction increase risk for infection. However, it is difficult to discern infection from CRS in the early (up to Day 30) and late (Days 31-180) periods after CARTx due to overlapping signs and symptoms. METHODS: We analyzed infectious complications and predictors of infection during the early and late periods after CARTx in 213 adult patients with malignancies over a 5-year period. RESULTS: Overall, 75 patients (35%) had at least one infection, most

CD200 является мощным новым фактором роста в Мультимиломе, зависящим от сигнала рецептора IGF1.

CD200 — это иммунный контрольно-пропускной пункт, безошибочно выраженный в 70% недавно диагностированных пациентов с множественной миеломой (ММ) и связанный с плохим исходом. Выражение CD200 клетками опухоли препятствует иммунной реакции через взаимодействие с CD200R и участвует в устойчивости к иммунной терапии. Однако его роль в опухоли остается слабой. В этом исследовании мы показываем, что клетки MM, перевыражающие CD200, представляют собой значительное пролиферативное преимущество в свободных культурных сыворотках, средних и клоногенных анализах. Преимущество роста клеток, опосредованное

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… Belonging to the immunoglobulin superfamily, it is widely expressed by various normal cell types, including thymocytes, B cells, activated T cells, resting dendritic cells, endothelial cells or neurons [ 1 , 2 ]. …

Автологичная трансплантация стволовых клеток гематопоиета стабилизирует атрофию сетчатки в множестве склероза.

Автологическая трансплантация стволовых клеток гематопоиета — это эффективное лечение агрессивных множественных рефракторов склероза для лечения заболеваний. Тем не менее, его воздействие на нейродегенерацию по-прежнему недостаточно изучено, и существует мало прогнозов биомаркеров для клинических результатов после аутологической трансплантации гематопоэтических стволовых клеток. Мы изучили, смягчает ли аутологическая трансплантация стволовых клеток процесс нейродегенерации сетчатки и предвосхищают ли показатели оптической согласованности, полученные на основе сетчатки, развитие инвалидности по

Mechanisms of T-cell Depletion in Tumors and Advances in Clinical Research.

T lymphocytes (T cells) are essential components of the adaptive immune system that play a vital role in identifying and eliminating infected and tumor cells. In tumor immunotherapy, T cells have emerged as a promising therapeutic strategy due to their high specificity, potent cytotoxic capability, long-lasting immune memory, and adaptability within immunotherapeutic approaches. However, tumors can evade the immune system by depleting T cells through various mechanisms, such as inhibitory receptor signaling, metabolic exhaustion, and physical barriers within the tumor microenvironment. This re

Paraneoplastic Syndrome After Kidney Transplantation: Frequency, Risk Factors, Differences to Paraneoplastic Occurrence of Glomerulonephritis in the Native Kidney, and Implications on Long-Term Kidney Graft Function.

Posttransplant malignancies are an important complication of solid organ transplantation. Kidney transplant recipients are at particularly high risk of cancer development. The most relevant risk factors of carcinogenesis are the use of immunosuppressive agents and oncogenic viral infections. Additionally, immune dysregulation caused by these factors may predispose to various types of organ damage. Paraneoplastic glomerular diseases are one of the most interesting and understudied cancer manifestations. The appropriate diagnosis of paraneoplastic glomerular damage can be challenging in kidney t

Lenalidomide treatment of Japanese patients with myelodysplastic syndromes with 5q deletion: a post-marketing surveillance study.

Lenalidomide was approved in Japan for the treatment of patients with myelodysplastic syndromes associated with a 5q deletion (del 5q-MDS) in August 2010. A post-marketing surveillance (PMS) study enrolled 173 patients with del 5q-MDS who started lenalidomide treatment between August 2010 and September 2011 (mean ± standard deviation [SD] age 72.4 ± 9.0 years) and observed for up to 6 cycles or 6 months. Adverse drug reactions (ADRs) and serious ADRs were reported in 78.0% and 50.9% of patients. The most commonly observed ADRs were thrombocytopenia or platelet count decreased (46.2%), neutrope

Do CAR-T and Allogeneic Stem Cell Transplant Both Have a Place in Lymphoid Neoplasms?

Allogeneic stem cell transplantation (allo-SCT) represented the first immunotherapy to treat hematologic malignancies: it has been considered as a cure for the disease and never as an approach to extend the life of patients. The success of allo-SCT derives both from the ability to treat patients with intensive chemoradiotherapy and from the potent graft-versus-leukemia effects mediated by donor immunity. Although considerable progress has been made in the last years, significant barriers still remain in the form of disease relapse, graft-versus-host disease, infectious complications, and regim

Experience of life quality from patients with aplastic anemia: a descriptive qualitative study.

BackgroundDespite the increasing incidence of aplastic anemia in China, few studies have explored its effect on the patients' quality of life from the perspective of these patients. In fact, patients with aplastic disorder live with the disease for a long time, and need to face a variety of difficult realities, including multiple disease symptoms and drug side effects, heavy burden of medical costs, difficulties in social reintegration, and negative emotional distress. Therefore, this study used descriptive qualitative research to explore the direct and rich quality-of-life experiences of pati

Hematopoietic stem cell transplantation in Zagreb: the first 40 years.

Hematopoietic stem cell transplantation is the most effective treatment for acute leukemia, severe aplastic anemia, and some hereditary hematological disorders. The principal source of stem cells in this procedure are bone marrow and peripheral blood cells. In recent years, the transplantation outcome has significantly improved. The availability of the donor no longer poses a problem, as transplantation has been performed routinely from related, unrelated, and haploidentical donors. A high success rate has been reported in elderly patients transplanted with reduced-intensity conditioning. Impr

Cytotoxicity of Gymnopilus purpureosquamulosus extracts on hematologic malignant cells through activation of the SAPK/JNK signaling pathway.

Treatment of hematologic malignancies is a formidable challenge for hematologists and there is an urgent need to identify safe and efficacious agents either via synthesis in the laboratory or isolation from natural products. Here, we report the cytotoxicity of extracts from mushroom Gymnopilus purpureosquamulosus Høil (G. pps) and describe its molecular mechanisms. Using leukemia, lymphoma and multiple myeloma cell lines, 28-35 ppm G. pps extract inhibited cell proliferation by ~46-79%, which correlates with activation of apoptosis as indicated by increase in annexin V-positive cells (~5-8-fol

Dipeptidyl Peptidase-4 Regulation of SDF-1/CXCR4 Axis: Implications for Cardiovascular Disease.

Dipeptidyl peptidase-4 (DPP4) is a ubiquitously expressed protease that regulates diverse number of physiological functions. As a dipeptidase, it exerts its catalytic effects on proteins/peptides with proline, alanine, or serine in the penultimate (P1) amino acid residue from the amino terminus. The evidence to date supports an important effect of DPP4 in catalytic cleavage of incretin peptides and this perhaps represents the main mechanism by which DPP4 inhibition improves glycemic control. DPP4 also plays an important role in the degradation of multiple chemokines of which stromal cell-deriv

The role of vitamin D in hematologic disease and stem cell transplantation.

Vitamin D is a steroid hormone with a broad range of biological effects ranging from the classical role as a mediator of calcium and phosphate balance to cellular differentiation and immune modulation. These effects impact normal and dysfunctional hematopoietic and immune function, which may allow an avenue for improved treatment and support of patients suffering from hematologic disorders. In this review, we will summarize the role of vitamin D in normal hematopoiesis, discuss ways in which vitamin D may improve outcomes, and discuss a potential role of vitamin D for treating hematologic diso

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… In the hematopoietic system the VDR receptor is expressed on various hematopoietic precursors as well as monocytes, some thymocytes, and activated B and T lymphocytes [ 8 ]. …

Ageing, autoimmunity and arthritis: senescence of the B cell compartment - implications for humoral immunity.

Immunosenescence is associated with a decline in both T and B lymphocyte function. Although aged individuals have normal numbers of B cells in the periphery and are capable of mounting robust humoral responses, the antibodies produced are generally of lower affinity and are less protective than those produced by young animals. Here we review multiple studies that address the mechanisms that contribute to this decline. Taken together, these studies suggest that age-associated loss of the ability to generate protective humoral immunity results in part from reduced B lymphopoiesis. As the output

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… In addition, autoantibodies against thymocytes and idio-typic determinants of BCR are detectable. Interestingly, the former have been implicated in impaired T cell poiesis [ 69 ], and the latter in suppression of specific B cell responses [ 70 ]. …

Understanding Autoimmunity: Mechanisms, Predisposing Factors, and Cytokine Therapies.

Autoimmunity refers to an organism's immune response against its own healthy cells, tissues, or components, potentially leading to irreversible damage to vital organs. Central and peripheral tolerance mechanisms play crucial roles in preventing autoimmunity by eliminating self-reactive T and B cells. The disruption of immunological tolerance, characterized by the failure of these mechanisms, results in the aberrant activation of autoreactive lymphocytes that target self-tissues, culminating in the pathogenesis of autoimmune disorders. Genetic predispositions, environmental exposures, and immun

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… In central tolerance (negative selection), immature T-cells (thymocytes) that strongly bind to self-antigens presented by thymic epithelial cells, dendritic cells, and macrophages undergo apoptosis. … Positive and negative selection of the T cell repertoire: What thymocytes see (and don’t see) Nat. Rev. Immunol. 2014;14:377–391. doi: 10.1038/nri3667. 35. Kishimoto H., Sprent J. Negative Selection in the Thymus Includes Semimature T Cells. J. Exp. …

Cannabidiol on the Path from the Lab to the Cancer Patient: Opportunities and Challenges.

Cannabidiol (CBD), a major non-psychotropic component of cannabis, is receiving growing attention as a potential anticancer agent. CBD suppresses the development of cancer in both in vitro (cancer cell culture) and in vivo (xenografts in immunodeficient mice) models. For critical evaluation of the advances of CBD on its path from laboratory research to practical application, in this review, we wish to call the attention of scientists and clinicians to the following issues: (a) the biological effects of CBD in cancer and healthy cells; (b) the anticancer effects of CBD in animal models and clin

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… In some cases, apoptosis mediated by CBD (16 µM) occurred earlier in cancer (EL-4 murine thymoma, 1 h) than in healthy tissue (thymocytes, 6 h) [ 33 ]. Although, in general, healthy tissue cells seem to be less sensitive to CBD cytotoxicity, some of their functional properties may be affected. … A comparative study on cannabidiol-induced apoptosis in murine thymocytes and EL-4 thymoma cells. Int. Immunopharmacol. 2008;8:732–740. doi: 10.1016/j.intimp.2008.01.018. 34. Zhang X., Qin Y., Pan Z., Li M., Liu X., Chen X., Qu G., Zhou L., Xu M., Zheng Q., et al. …

Автономная гематопоэтическая трансплантация уменьшает воспаление мозга и аксоглиальные повреждения биомаркеров при множественном склерозе.

Аутологическая трансплантация стволовых клеток (AHSCT) может вызвать долгосрочную иммунную терпимость и остроту болезней у пациентов с сильным множественным склерозом (MS), однако основные механизмы не вполне понятны. Мы гипотезуем, что AHSCT вызовет постоянное снижение в провокационных цитокинах, хемокинах и аксолиальных повреждениях биомаркеров в сыворотке и CSF.МЕТОДЫ: Продольная сыворотка и пробы CSF были получены из 24 :: участники процесса по делу HALT-MS с сильными MS, проходящими через AHSCT ( < < AHSCT > > )NCT00288626), с сывороткой, собираемой в 9 период времени с момент

Помимо типичного синдрома нейротоксичности, связанного с иммунным эффектом, характеризирующего неиммунный эффект, связанный с нейротоксичным синдромом нейротоксичности, при ретроспективном анализе химерика антигенного рецептора Т-клеток.

ЦЫПЛЕНОК: Химерическая антигенная терапия (CAR) Т-клеточная терапия революционизировала лечение рецидивных/отверженных гематологовых магнатов. В то время как синдром нейротоксичности, связанный с иммунным эффектом клеток (ИКАНС), является широко признанным осложнением, расширение клинического применения выявило явные неврологические осложнения, не связанные с ИКАНС, которые бросают вызов стандартным подходам к диагностике и управлению. Мы характеризуем клинические особенности и результаты этих неклассических презентаций. МЕТОДЫ: Был проведен ретроспективный анализ 357 - пациенты, получающие ко