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Targeting Members of the Chemokine Family as a Novel Approach to Treating Neuropathic Pain.

Neuropathic pain is a debilitating condition that affects millions of people worldwide. Numerous studies indicate that this type of pain is a chronic condition with a complex mechanism that tends to worsen over time, leading to a significant deterioration in patients' quality of life and issues like depression, disability, and disturbed sleep. Presently used analgesics are not effective enough in neuropathy treatment and may cause many side effects due to the high doses needed. In recent years, many researchers have pointed to the important role of chemokines not only in the development and ma

Selected Abstracts from the 13th Annual Meeting of the Clinical Immunology Society: 2022 Annual Meeting: Immune Deficiency and Dysregulation North American Conference

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… The Treg cell-specific demethylated region (TSDR) of FOXP3 was previously shown to be overrepresented in its unmethylated state in IPEX patients’ whole blood DNA. Here, we aimed to assess TSDR analysis for characterization of disease severity and interpretation of novel FOXP3 variants in IPEX. … We show that TSDR/CD4 demethylation is consistently elevated in all IPEX patients and nominally higher among the typical and severe cases as compared to the atypical cases. …

Cancer stem cells: advances in knowledge and implications for cancer therapy.

Cancer stem cells (CSCs), a small subset of cells in tumors that are characterized by self-renewal and continuous proliferation, lead to tumorigenesis, metastasis, and maintain tumor heterogeneity. Cancer continues to be a significant global disease burden. In the past, surgery, radiotherapy, and chemotherapy were the main cancer treatments. The technology of cancer treatments continues to develop and advance, and the emergence of targeted therapy, and immunotherapy provides more options for patients to a certain extent. However, the limitations of efficacy and treatment resistance are still i

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… dedifferentiation of daughter crypt cells and replenishment of stem cells, which is dependent on the transcription factor Achaete-Scute Homolog 2 (ASCL2). 132 Mature pigment-producing melanocytes can also dedifferentiate into tumor progenitors of cutaneous melanoma induced by mutant BRAF. 133 PGC7 induces promoter demethylation …

Processes and therapeutic perspectives of acylation modifications of lysine and cysteine in tumors.

Acylation modification plays a crucial role in tumor progression through altering protein homeostasis and localization. However, a comprehensive summary of these processes is lacking. Protein acylation modifications are comprehensively summarized and categorized based on the amino acids that are modified. This review focuses on modifications of the lysine (acetylation, succinylation, crotonylation, malonylation, and glutarylation) and cysteine (myristoylation and palmitoylation) groups. The key enzymes involved in the occurrence and erasure of different modifications, as well as their effects

Curcumin Rewires the Tumor Metabolic Landscape: Mechanisms and Clinical Prospects.

Metabolic reprogramming is a fundamental hallmark and a key driver of malignant tumors. By reshaping glucose, lipid, and amino acid metabolism, as well as mitochondrial function, it sustains the abnormal proliferation and survival of tumor cells, making it a crucial target for anti-tumor therapy. Curcumin, a natural multi-target compound, exhibits unique advantages in intervening in tumor metabolic reprogramming due to its low toxicity and broad-spectrum regulatory properties. In various tumor models, it can directly modulate the activity of key glycolytic enzymes, such as hexokinase 2, lactat

Therapeutic targets and biomarkers of tumor immunotherapy: response versus non-response.

Cancers are highly complex diseases that are characterized by not only the overgrowth of malignant cells but also an altered immune response. The inhibition and reprogramming of the immune system play critical roles in tumor initiation and progression. Immunotherapy aims to reactivate antitumor immune cells and overcome the immune escape mechanisms of tumors. Represented by immune checkpoint blockade and adoptive cell transfer, tumor immunotherapy has seen tremendous success in the clinic, with the capability to induce long-term regression of some tumors that are refractory to all other treatm

Interplay Between Poly(ADP-ribosyl)ation and Specific Inner Cellular Events That Suggest Combination Strategies for Overcoming PARP Inhibitor Resistance.

Therapeutic resistance remains a major obstacle to durable cancer control, with functional reprogramming of the DNA damage response (DDR) network playing a central role. The poly(ADP-ribose) polymerase (PARP) family, particularly PARP1 and PARP2, is crucial for maintaining genomic integrity. By exploiting synthetic lethality, PARP inhibitors (PARPi) selectively target tumors with homologous recombination deficiency (HRD) and are integral to precision therapy in ovarian, breast, and prostate cancers. However, over 40% of patients with BRCA1/2 alterations develop resistance, and patient eligibil

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… Promoter demethylation of BRCA1 or RAD51C, for example, can reactivate gene expression and HR activity without correcting the underlying DNA sequence [ 109 , 110 ]. …

Harnessing live vectors for cancer vaccines: Advancing therapeutic immunotherapy.

Cancer vaccines represent a promising approach within immunotherapies. These vaccines are tailored to target tumor-specific antigens, thereby offering a precision approach to cancer treatment. The key principles in developing therapeutic cancer vaccines include identifying appropriate vaccine targets and selecting effective vaccine delivery platforms. These delivery platforms are diverse and have evolved to enhance the immune response. This review explores live cancer vaccines and the biological entities involved. Live cancer vaccines leverage the use of various biological entities to stimulat

Iron in the Tumor Microenvironment-Connecting the Dots.

Iron metabolism and tumor biology are intimately linked. Iron facilitates the production of oxygen radicals, which may either result in iron-induced cell death, ferroptosis, or contribute to mutagenicity and malignant transformation. Once transformed, malignant cells require high amounts of iron for proliferation. In addition, iron has multiple regulatory effects on the immune system, thus affecting tumor surveillance by immune cells. For these reasons, inconsiderate iron supplementation in cancer patients has the potential of worsening disease course and outcome. On the other hand, chronic im

Novel drug targets for personalized precision medicine in relapsed/refractory diffuse large B-cell lymphoma: a comprehensive review.

Diffuse large B-cell lymphoma (DLBCL) is a clinically heterogeneous lymphoid malignancy and the most common subtype of non-Hodgkin's lymphoma in adults, with one of the highest mortality rates in most developed areas of the world. More than half of DLBLC patients can be cured with standard R-CHOP regimens, however approximately 30 to 40 % of patients will develop relapsed/refractory disease that remains a major cause of morbidity and mortality due to the limited therapeutic options.Recent advances in gene expression profiling have led to the identification of at least three distinct molecular

The efficacy and applicability of chimeric antigen receptor (CAR) T cell-based regimens for primary bone tumors: A comprehensive review of current evidence.

Primary bone tumors (PBT), although rare, could pose significant mortality and morbidity risks due to their high incidence of lung metastasis. Survival rates of patients with PBTs may vary based on the tumor type, therapeutic interventions, and the time of diagnosis. Despite advances in the management of patients with these tumors over the past four decades, the survival rates seem not to have improved significantly, implicating the need for novel therapeutic interventions. Surgical resection with wide margins, radiotherapy, and systemic chemotherapy are the main lines of treatment for PBTs. N

Different origin-derived exosomes and their clinical advantages in cancer therapy.

Exosomes, as a class of small extracellular vesicles closely related to the biological behavior of various types of tumors, are currently attracting research attention in cancer diagnosis and treatment. Regarding cancer diagnosis, the stability of their membrane structure and their wide distribution in body fluids render exosomes promising biomarkers. It is expected that exosome-based liquid biopsy will become an important tool for tumor diagnosis in the future. For cancer treatment, exosomes, as the "golden communicators" between cells, can be designed to deliver different drugs, aiming to ac

Tumor microenvironment signaling and therapeutics in cancer progression.

Tumor development and metastasis are facilitated by the complex interactions between cancer cells and their microenvironment, which comprises stromal cells and extracellular matrix (ECM) components, among other factors. Stromal cells can adopt new phenotypes to promote tumor cell invasion. A deep understanding of the signaling pathways involved in cell-to-cell and cell-to-ECM interactions is needed to design effective intervention strategies that might interrupt these interactions. In this review, we describe the tumor microenvironment (TME) components and associated therapeutics. We discuss t

Расширение горизонта: потенциальное применение элементов ЦАР-Т сверх нынешних показателей.

Проектирование иммунных клеток для лечения гематологических заболеваний стало одним из основных направлений исследований с тех пор, как в B-ALL были достигнуты первые заметные успехи в лечении CAR-T-клеток. В настоящее время можно лечить несколько заболеваний в условиях высокой терапии или рецидива. В настоящее время для острого лимфоболического лейкемии (ALL), диффузной лимфомы B-клеток (DLBCL), лимфомы мантичной клетки (MCL), множественной миеломы (MM) и фолликулярной лимфомы (FL) утвержден ряд методов лечения CD19- или BCMA-клеток. Применение этих методов значительно улучшило результативнос

The Inclusion of Dietary and Medicinal Mushrooms into Translational Oncology: Pros and Cons at the Molecular Level.

Mushrooms are valued for their nutritional qualities and have been used in traditional medicine since the Neolithic era. They exhibit various bioactivities, including antioxidant, hypocholesterolemic, immunomodulatory, and anticancer effects. The anticancer effects arise via direct action on tumor cells and indirect modulation of the immune system; the latter is the predominant mechanism. Numerous studies indicate that various mushroom species are potent immunostimulants because their cell wall polysaccharides and proteoglycans are recognized by intestinal immune cells. This enhances antitumor

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… Its water-miscible prodrug, PEG5-grifolin, exhibits superior demethylation activity compared to 5-aza-2′-deoxycytidine in preclinical studies and is highly soluble [ 240 ]. Therefore, grifolin is a promising agent for downregulating DNMT1. …

Targeting LAG-3, TIM-3, and TIGIT for cancer immunotherapy.

In one decade, immunotherapy based on immune checkpoint blockades (ICBs) has become a new pillar of cancer treatment following surgery, radiation, chemotherapy, and targeted therapies. However, not all cancer patients benefit from single or combination therapy with anti-CTLA-4 and anti-PD-1/PD-L1 monoclonal antibodies. Thus, an increasing number of immune checkpoint proteins (ICPs) have been screened and their effectiveness evaluated in preclinical and clinical trials. Lymphocyte activation gene-3 (LAG-3), T cell immunoglobulin and mucin-domain-containing-3 (TIM-3), and T cell immunoreceptor w

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… In addition, anti-TIM-3 mAbs combined with conventional chemotherapy or demethylation therapy showed increased antitumor effects and are novel options that showed initial efficacy, particularly in the treatment of MDS and AML. …

Biochemical and Clinical Impact of Organic Uremic Retention Solutes: A Comprehensive Update.

In this narrative review, the biological/biochemical impact (toxicity) of a large array of known individual uremic retention solutes and groups of solutes is summarized. We classified these compounds along their physico-chemical characteristics as small water-soluble compounds or groups, protein bound compounds and middle molecules. All but one solute (glomerulopressin) affected at least one mechanism with the potential to contribute to the uremic syndrome. In general, several mechanisms were influenced for each individual solute or group of solutes, with some impacting up to 7 different biolo

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… Homocysteine Homocysteine (Hcy) is a sulphur-containing amino acid produced by demethylation of methionine and a cardiovascular risk factor in the general population. Its concentration is markedly increased in end stage kidney disease (ESKD) [ 236 ]. …

The interplay of exercise and green tea: a new road in cancer therapy.

Exercise is one of the most important activities for every individual due to its proven health beneficials. Several investigations have highlighted the advantageous impacts of aerobic exercise, largely attributed to its capacity to enhance the body's capability to defend against threats against oxidative stress. The information currently accessible suggests that adding regular aerobic exercise to a daily routine greatly decreases the chances of developing serious cancer and passing away. An unevenness in the levels of free radicals and the body's antioxidant defenses, made up of enzyme and non

Cancer-Associated Fibroblasts: Heterogeneity, Cancer Pathogenesis, and Therapeutic Targets.

Cancer-associated fibroblasts (CAFs) are functionally diverse stromal regulators that orchestrate tumor progression, metastasis, and therapy resistance through dynamic crosstalk within the tumor microenvironment (TME). Recent advances in single-cell multiomics and spatial transcriptomics have identified conserved CAF subtypes with distinct molecular signatures, spatial distributions, and context-dependent roles, highlighting their dual capacity to promote immunosuppression or restrain tumor growth. However, therapeutic strategies struggle to reconcile this functional duality, hindering clinica

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… FTO‐mediated m6A demethylation in conjunctival melanoma CAFs stabilizes VEGFA and EGR1 transcripts, whereas gut microbiota‐derived butyrate suppresses angiogenesis by inhibiting histone deacetylase 3 and reducing SULF1 expression in CRC CAFs [91, 93 ]. …

Генетическая основа болезни.

Генетика в той или иной степени играет определенную роль во всех заболеваниях. Изменения в нашей ДНК и различия в том, как эта ДНК функционирует (одиночка или комбинация), наряду с окружающей средой (которая включает образ жизни), способствуют болезнетворным процессам. В рамках этого обзора изучается генетическая основа человеческих заболеваний, включая однородные генетические расстройства, хромосомные диспропорции, эпигенетические, раковые и сложные расстройства, и рассматривается вопрос о том, каким образом наше понимание и технологические достижения могут быть использованы для обеспечения н