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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

Abstracts from the 13th International Conference for Healthcare and Medical Students (ICHAMS).

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… The pathogenesis of tumour progression has been found to be influenced by RNA methylation, most noticeably N6-methyadenosine (m6A). Aberrantly expression of FTO, a methyl eraser, has been found to be associated with poor outcomes in ER+ breast cancer. …

Targeting the proteasome in cancer therapy: development and future opportunities in natural products.

BACKGROUND: The ubiquitin-proteasome pathway is a critical therapeutic target in malignancies, particularly multiple myeloma. The development of proteasome inhibitors (PIs) has marked a milestone in multiple myeloma therapy and now constitutes the backbone of frontline treatment regimens. However, primary and acquired resistance remain a major challenge, underscoring the need to identify new PIs as well as agents that can resensitize resistant cells. METHOD: This review provides an overview of the current clinical applications of PIs and offers a comprehensive summary of natural products that

Genome-edited allogeneic CAR-T cells: the next generation of cancer immunotherapies.

Chimeric Antigen Receptor T (CAR-T) cell therapy has revolutionized cancer immunotherapy, particularly in hematological malignancies. However, the clinical application of autologous CAR-T cells faces significant high cost and manufacturing challenges. Universal allogeneic CAR-T cells, derived from healthy donors, represent a promising solution to these obstacles. These "off-the-shelf" therapies aim to reduce the complexity and cost of CAR-T production. Despite exciting advancements in genome-editing technologies and promising clinical trial data, significant challenges remain, including graft-

Current drugs for HIV-1: from challenges to potential in HIV/AIDS.

The human immunodeficiency virus (HIV) persists in latently infected CD4+T cells and integrates with the host genome until cell death. Acquired immunodeficiency syndrome (AIDS) is associated with HIV-1. Possibly, treating HIV/AIDS is an essential but challenging clinical goal. This review provides a detailed account of the types and mechanisms of monotherapy and combination therapy against HIV-1 and describes nanoparticle and hydrogel delivery systems. In particular, the recently developed capsid inhibitor (Lenacapavir) and the Ainuovirine/tenofovir disoproxil fumarate/lamivudine combination (

Resveratrol: Molecular Mechanisms, Health Benefits, and Potential Adverse Effects.

Resveratrol (RES), a naturally occurring polyphenolic compound, has garnered significant attention due to its diverse biological activities, which include anti-inflammatory, antioxidant, and antiaging properties. This review synthesizes current evidence concerning the molecular mechanisms, therapeutic efficacy, and safety profile of RES across a variety of pathologies, with an emphasis on the latest research conducted in recent years. Mechanistically, RES is known to modulate critical signaling pathways such as the activation of sirtuin 1. These actions collectively contribute to the attenuati

The trinity of T cell engagement: navigating the molecular and clinical landscape of CAR-T, TILs, and TCEs in the war against cancer.

The advent of cancer immunotherapy has fundamentally restructured the oncological paradigm, moving away from agents that directly target tumor cell kinetics toward strategies that empower the host immune system to recognize and eliminate malignancy. Central to this revolution is the cytotoxic T lymphocyte (CTL), now harnessed as a potent "living drug" through engineered and naturally selected modalities. This review provides a critical, in-depth examination of the three dominant pillars of T cell-driven therapies: Chimeric Antigen Receptor T-cell (CAR-T) therapy, Tumor-Infiltrating Lymphocyte

Развитие микробиотерапии: роль синтетической биологии в инженерных микробных сообществах для точной медицины.

В последние годы исследования в области микробиотических исследований и синтетической биологии были посвящены изучению новых подходов к микробным манипуляциям в терапевтических целях. Тем не менее, по этому аспекту имеется фрагментированная информация с ключевыми идеями, разбросанными по различным дисциплинам, таким, как молекулярная биология, генетика, биоинженерия и медицина. Цель этого обзора заключается в создании преобразующего потенциала синтетической биологии в плане развития исследований и лечения микробиоме, что имеет значительные последствия для здравоохранения, сельского хозяйства и

Advances in nanomaterial-mediated CRISPR/Cas delivery: from lipid nanoparticles to vesicle-derived systems.

Gene and genome editing therapies are increasingly connected with nanomaterials, which protect and transport fragile nucleic acids and CRISPR/Cas systems through biological barriers safely and accurately. This review discusses how different nanocarriers, including lipid-based, polymeric, inorganic, and vesicle-derived systems, can improve delivery efficiency, cell targeting, endosomal escape, and intracellular movement for gene and genome editing. It summarizes findings from early clinical and preclinical studies, comparing several carrier types such as ionizable lipid nanoparticles, polymeric

Integrative meta-analysis identifies microRNA-regulated networks in infantile hemangioma.

BackgroundHemangioma is a common benign tumor in the childhood; however our knowledge about the molecular mechanisms of hemangioma development and progression are still limited. Currently, microRNAs (miRNAs) have been shown as gene expression regulators with an important role in disease pathogenesis. Our goals were to identify miRNA-mRNA expression networks associated with infantile hemangioma.MethodsWe performed a meta-analysis of previously published gene expression datasets including 98 hemangioma samples. Deregulated genes were further used to identify microRNAs as potential regulators of

Breast cancer cells induce osteolytic bone lesions in vivo through a reduction in osteoblast activity in mice.

Bone metastases are severely debilitating and have a significant impact on the quality of life of women with metastatic breast cancer. Treatment options are limited and in order to develop more targeted therapies, improved understanding of the complex mechanisms that lead to bone lesion development are warranted. Interestingly, whilst prostate-derived bone metastases are characterised by mixed or osteoblastic lesions, breast-derived bone metastases are characterised by osteolytic lesions, suggesting unique regulatory patterns. This study aimed to measure the changes in bone formation and bone

Mapping the function of MicroRNAs as a critical regulator of tumor-immune cell communication in breast cancer and potential treatment strategies.

Among women, breast cancer ranks as the most prevalent form of cancer, and the presence of metastases significantly reduces prognosis and diminishes overall survival rates. Gaining insights into the biological mechanisms governing the conversion of cancer cells, their subsequent spread to other areas of the body, and the immune system's monitoring of tumor growth will contribute to the advancement of more efficient and targeted therapies. MicroRNAs (miRNAs) play a critical role in the interaction between tumor cells and immune cells, facilitating tumor cells' evasion of the immune system and p

Nuclear receptors in health and disease: signaling pathways, biological functions and pharmaceutical interventions.

Nuclear receptors (NRs) are a large family of ligand-dependent transcription factors that regulate the expression of a wide range of target genes in response to endogenous and exogenous ligands, including steroid hormones, thyroid hormone, vitamin D, retinoic acid, fatty acids, and oxidative steroids. Upon ligand binding, nuclear receptors form dimer complexes with transcriptional cofactors, which interact with specific DNA sequences in the promoter or enhancer regions of target genes to modulate gene expression. This process plays a crucial role in many physiological processes such as reprodu

Ferroptosis: a new dawn in the treatment of acute lymphoblastic leukemia.

Acute lymphoblastic leukemia poses substantial challenges in therapeutic management. As a novel form of programmed cell death, ferroptosis has emerged as a promising research direction in cancer therapy. Studies have emphasized the pivotal role of ferroptosis in ALL, indicating that targeting this pathway could provide a novel therapeutic strategy. This article systematically reviews the molecular regulatory mechanisms of ferroptosis in ALL and explores its potential clinical applications in the treatment and prognostic evaluation of the disease.

Anticancer Properties of Plectranthus ornatus-Derived Phytochemicals Inducing Apoptosis via Mitochondrial Pathway.

Since cancer treatment by radio- and chemotherapy has been linked to safety concerns, there is a need for new and alternative anticancer drugs; as such, compounds isolated from plants represent promising candidates. The current study investigates the anticancer features of halimane (11R*,13E)-11-acetoxyhalima-5,13-dien-15-oic acid (HAL) and the labdane diterpenes 1α,6β-diacetoxy-8α,13R*-epoxy-14-labden-11-one (PLEC) and forskolin-like 1:1 mixture of 1,6-di-O-acetylforskolin and 1,6-di-O-acetyl-9-deoxyforskolin (MRC) isolated from Plectranthus ornatus in MCF7 and FaDu cancer cell lines. Cytotox

Role of Exosomal Non-Coding RNAs in Bone-Related Diseases.

Bone-related diseases seriously affect the lives of patients and carry a heavy economic burden on society. Treatment methods cannot meet the diverse clinical needs of affected patients. Exosomes participate in the occurrence and development of many diseases through intercellular communication, including bone-related diseases. Studies have shown that exosomes can take-up and "package" non-coding RNAs and "deliver" them to recipient cells, thereby regulating the function of recipient cells. The exosomal non-coding RNAs secreted by osteoblasts, osteoclasts, chondrocytes, and other cells are invol

Pluripotent Stem Cells for Disease Modeling and Drug Discovery in Niemann-Pick Type C1.

The lysosomal storage disorders Niemann-Pick disease Type C1 (NPC1) and Type C2 (NPC2) are rare diseases caused by mutations in the NPC1 or NPC2 gene. Both NPC1 and NPC2 are proteins responsible for the exit of cholesterol from late endosomes and lysosomes (LE/LY). Consequently, mutations in one of the two proteins lead to the accumulation of unesterified cholesterol and glycosphingolipids in LE/LY, displaying a disease hallmark. A total of 95% of cases are due to a deficiency of NPC1 and only 5% are caused by NPC2 deficiency. Clinical manifestations include neurological symptoms and systemic

The Role of the CREB Protein Family Members and the Related Transcription Factors in Radioresistance Mechanisms.

In the framework of space flight, the risk of radiation carcinogenesis is considered a "red" risk due to the high likelihood of occurrence as well as the high potential impact on the quality of life in terms of disease-free survival after space missions. The cyclic AMP response element-binding protein (CREB) is overexpressed both in haematological malignancies and solid tumours and its expression and function are modulated following irradiation. The CREB protein is a transcription factor and member of the CREB/activating transcription factor (ATF) family. As such, it has an essential role in a

Therapeutic approaches in myelofibrosis and myelodysplastic/myeloproliferative overlap syndromes.

The discovery of JAK2 (V617F) a decade ago led to optimism for a rapidly developing treatment revolution in Ph(-) myeloproliferative neoplasms. Unlike BCR-ABL, however, JAK2 was found to have a more heterogeneous role in carcinogenesis. Therefore, for years, development of new therapies was slow, despite standard treatment options that did not address the overwhelming symptom burden in patients with primary myelofibrosis (MF), post-essential thrombocythemia MF, post-polycythemia vera MF, and myelodysplastic syndrome (MDS)/myeloproliferative neoplasm (MPN) syndromes. JAK-STAT inhibitors have ch

An understanding of mitochondria and its role in targeting nanocarriers for diagnosis and treatment of cancer.

Nanotechnology has changed the entire paradigm of drug targeting and has shown tremendous potential in the area of cancer therapy due to its specificity. In cancer, several targets have been explored which could be utilized for the better treatment of disease. Mitochondria, the so-called powerhouse of cell, portrays significant role in the survival and death of cells, and has emerged as potential target for cancer therapy. Direct targeting and nanotechnology based approaches can be tailor-made to target mitochondria and thus improve the survival rate of patients suffering from cancer. With thi