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Parthenolide Inhibits the Proliferation of MDA-T32 Papillary Thyroid Carcinoma Cells in Vitro and in Mouse Tumor Xenografts and Activates Autophagy and Apoptosis by Downregulation of the Mammalian Target of Rapamycin (mTOR)/PI3K/AKT Signaling Pathway.

BACKGROUND This study aimed to examine the effects of the sesquiterpene lactone, parthenolide, on migration, autophagy, and apoptosis of MDA-T32 human papillary thyroid carcinoma cells in vitro and in mouse tumor xenografts. MATERIAL AND METHODS Cell proliferation and viability of MDA-T32 human papillary thyroid carcinoma cells were determined by MTT assay, and cell migration was studied using a transwell assay. Fluorescence microscopy using acridine orange (AO) and ethidium bromide (EB) staining evaluated apoptosis. Transmission electron microscopy was used to study the effects of parthenolid

Efficacy and safety of selinexor-based regimens as first-line treatments for elderly patients with diffuse large B-cell lymphoma: a real-world study.

PURPOSE: This study aimed to evaluate the efficacy and safety of selinexor-based regimens as first-line treatments for elderly patients with diffuse large B-cell lymphoma (DLBCL). METHODS: A retrospective analysis of 16 elderly patients with DLBCL who received selinexor-based regimens as first-line treatments at Sun Yat-sen University Cancer Center from November 2021 to September 2023 was conducted. The primary endpoint was the objective response rate (ORR), while the secondary endpoints included progression-free survival (PFS), duration of response (DOR), and safety. RESULTS: Among the 16 e

Updates in Anthracycline-Mediated Cardiotoxicity.

Cardiotoxicity is one of the main adverse effects of chemotheraphy, affecting the completion of cancer therapies and the short- and long-term quality of life. Anthracyclines are currently used to treat many cancers, including the various forms of leukemia, lymphoma, melanoma, uterine, breast, and gastric cancers. World Health Organization registered anthracyclines in the list of essential medicines. However, anthracyclines display a major cardiotoxicity that can ultimately culminate in congestive heart failure. Taking into account the growing rate of cancer survivorship, the clinical significa

The Potential and Prospects of Marine Drugs in Intervening Nerve-Tumor Crosstalk.

The bidirectional crosstalk between the nervous system and tumors has emerged as a transformative new frontier in both precision oncotherapy and mechanism-driven cancer pain management. Marine natural products with inherent neuroactive properties exhibit unparalleled intervention advantages for targeting this complex pathophysiological axis. Herein, we systematically and prospectively dissect the multi-layered bidirectional communication between the nervous system and malignancies, comprehensively summarize the pivotal contributions of marine-derived bioactive molecules to advances in neurosci

The Complosome: An Emerging Intracellular Complement Network in Cancer Development and Therapy.

The complement system is traditionally recognized as a major effector of innate immunity, essential for pathogen clearance, inflammation and the maintenance of tissue homeostasis. In recent years, however, its role in cancer has been substantially redefined. Beyond its canonical extracellular activity, complement has emerged as a multifaceted regulator of tumor biology, acting not only within the tumor microenvironment but also intracellularly through the recently described intracellular complement system (complosome). While extracellular complement primarily shapes immune responses and the tu

Молекулярные модели, связанные с ущербом от митохондриала: нейроиммуномодуляторы в патофизиологии центральной нервной системы.

Нейроинфламмация способствует широкому спектру нейродегенеративных заболеваний, включая болезнь Альцгеймера, болезнь Паркинсона, болезнь Хантингтона и множественный склероз. Его движут неевропейские глиальные клетки, главным образом микроглии и астроциты. Микроглии являются постоянными иммунными клетками центральной нервной системы, в то время как астроциты являются основными элементами поддержки нейронных функций, но могут также участвовать в нейроиммунной реакции. Оба этих типа глиальных клеток могут стать реактивными при обнаружении определенных внутриклеточных молекул, которые появляются в

Mitochondrial Kv1.3 Channels as Target for Treatment of Multiple Myeloma.

Despite several new developments in the treatment of multiple myeloma, all available therapies are only palliative without curative potential and all patients ultimately relapse. Thus, novel therapeutic options are urgently required to prolong survival of or to even cure myeloma. Here, we show that multiple myeloma cells express the potassium channel Kv1.3 in their mitochondria. The mitochondrial Kv1.3 inhibitors PAPTP and PCARBTP are efficient against two tested human multiple myeloma cell lines (L-363 and RPMI-8226) and against ex vivo cultured, patient-derived myeloma cells, while healthy b

Clinical Applications and Anticancer Effects of Antimicrobial Peptides: From Bench to Bedside.

Cancer is a multifaceted global health issue and one of the leading causes of death worldwide. In recent years, medical science has achieved great advances in the diagnosis and treatment of cancer. Despite the numerous advantages of conventional cancer therapies, there are major drawbacks including severe side effects, toxicities, and drug resistance. Therefore, the urgency of developing new drugs with low cytotoxicity and treatment resistance is increasing. Antimicrobial peptides (AMPs) have attracted attention as a novel therapeutic strategy for the treatment of various cancers, targeting tu

Exosomes play a role in multiple myeloma bone disease and tumor development by targeting osteoclasts and osteoblasts.

Progression of multiple myeloma (MM) is largely dependent on the bone marrow (BM) microenvironment wherein communication through different factors including extracellular vesicles takes place. This cross-talk not only leads to drug resistance but also to the development of osteolysis. Targeting vesicle secretion could therefore simultaneously ameliorate drug response and bone disease. In this paper, we examined the effects of MM exosomes on different aspects of osteolysis using the 5TGM1 murine model. We found that 5TGM1 sEVs, or 'exosomes', not only enhanced osteoclast activity, they also blo

Minimally effective concentration of zoledronic acid to suppress osteoclasts in vitro.

Zoledronic acid is regarded as the most potent bisphosphonate and is widely used in patients with osteoporosis; however, its side effects, including acute-phase reactions, gastrointestinal complaints, renal dysfunction and bisphosphonate-associated osteonecrosis impair the safety and quality of life of patients. The present study was designed to determine the minimal effective concentration of zoledronic acid through testing the dose-dependent effects of zoledronic acid on osteoclast suppression. A primary culture of bone marrow mononuclear cells obtained from C57 mice (age, 6 weeks) was estab

Protein-Based Adjuvants for Vaccines as Immunomodulators of the Innate and Adaptive Immune Response: Current Knowledge, Challenges, and Future Opportunities.

New-generation vaccines, formulated with subunits or nucleic acids, are less immunogenic than classical vaccines formulated with live-attenuated or inactivated pathogens. This difference has led to an intensified search for additional potent vaccine adjuvants that meet safety and efficacy criteria and confer long-term protection. This review provides an overview of protein-based adjuvants (PBAs) obtained from different organisms, including bacteria, mollusks, plants, and humans. Notably, despite structural differences, all PBAs show significant immunostimulatory properties, eliciting B-cell- a

Apoptosis and (in) Pain-Potential Clinical Implications.

The deregulation of apoptosis is involved in the development of several pathologies, and recent evidence suggests that apoptosis may be involved in chronic pain, namely in neuropathic pain. Neuropathic pain is a chronic pain state caused by primary damage or dysfunction of the nervous system; however, the details of the molecular mechanisms have not yet been fully elucidated. Recently, it was found that nerve endings contain transient receptor potential (TRP) channels that sense and detect signals released by injured tissues and respond to these damage signals. TRP channels are similar to the

Calcium-Permeable Channels Cooperation for Rheumatoid Arthritis: Therapeutic Opportunities.

Rheumatoid arthritis is a common autoimmune disease that results from the deposition of antibodies-autoantigens in the joints, leading to long-lasting inflammation. The main features of RA include cartilage damage, synovial invasion and flare-ups of intra-articular inflammation, and these pathological processes significantly reduce patients' quality of life. To date, there is still no drug target that can act in rheumatoid arthritis. Therefore, the search for novel drug targets has become urgent. Due to their unique physicochemical properties, calcium ions play an important role in all cellula

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

Vision of Life's Code: Molecular Probe Nanoarchitectonics for Deep RNA/DNA Illumination.

Visualization of RNA and DNA provides a window of opportunity for the early detection of multiple diseases and approaches to manipulate them before any pathological processes occur. However, current imaging systems often fail to meet these demands due to the need for multiple RNA and DNA chemical probes, which increases experimental complexity, reduces awareness of false positives, and limits imaging accuracy in complex biosystems. In this work, we identify the key challenges associated with using multiple probes for RNA and DNA imaging and analyze the mechanisms and performance of existing im

Совпадение в полном тексте источника
… Due to the highly specific nature of nuclear pores, it remains difficult for small molecular probes or other organic molecules to pass through and enter the nucleus. …

The interplay of mitochondrial dysfunction and altered metabolic pathways in glioblastoma.

Glioblastoma (GBM) is the most aggressive and lethal primary brain tumor, characterized by rapid progression, treatment resistance, and poor prognosis, with a survival rate of less than five years despite advances in medical interventions. A hallmark of GBM is metabolic reprogramming, which supports tumor growth and progression. Mitochondrial dysfunction plays a critical role in this metabolic shift by altering energy production and disrupting key cellular pathways. However, the precise molecular mecha-nisms underlying these alterations remain inadequately understood. This review highlights th

Свойства антиракера ВИЧ-ингибатора Нелфинавира.

Традиционные методы лечения рака могут потерять свою эффективность после появления новых мутации или развития химиотерапии. Несвоевременная диагностика, высокая стоимость лечения и потребность в высокоэффективной инфраструктуре для лечения раковых заболеваний затрудняют доступ к надлежащему лечению в условиях с низким уровнем доходов и ограниченными ресурсами. Переориентация утвержденных лекарственных средств на лечение рака может привести к снижению стоимости и сокращению сроков разработки новых лекарственных средств и к ускорению появления новых и эффективных вариантов лечения для нуждающихс

Bortezomib Increased Vascular Permeability by Decreasing Cell-Cell Junction Molecules in Human Pulmonary Microvascular Endothelial Cells.

Bortezomib (BTZ), a chemotherapeutic drug used to treat multiple myeloma, induces life-threatening side effects, including severe pulmonary toxicity. However, the mechanisms underlying these effects remain unclear. The objectives of this study were to (1) investigate whether BTZ influences vascular permeability and (2) clarify the effect of BTZ on the expression of molecules associated with cell-cell junctions using human pulmonary microvascular endothelial cells in vitro. Clinically relevant concentrations of BTZ induced limited cytotoxicity and increased the permeability of human pulmonary m

Targeting Nuclear Exporter Protein XPO1/CRM1 in Gastric Cancer.

Gastric cancer remains an unmet clinical problem in urgent need of newer and effective treatments. Here we show that the nuclear export protein, Exportin 1 (XPO1, chromosome region maintenance 1 or CRM1), is a promising molecular target in gastric cancer. We demonstrate significant overexpression of XPO1 in a cohort of histologically diverse gastric cancer patients with primary and metastatic disease. XPO1 RNA interference suppressed gastric cancer cell growth. Anti-tumor activity was observed with specific inhibitor of nuclear export (SINE) compounds (selinexor/XPOVIO), second-generation comp

Совпадение в полном тексте источника
… The XPO1-cargo protein complex travels through the nuclear pore and is released in the cytoplasm upon hydrolysis of GTP-binding nuclear protein RanGTP (RanGTP) to GTP-binding nuclear protein Ran GDP (Ran-GDP) [ 8 , 9 ]. Many tumor types overexpress XPO1 compared to normal tissue [ 10 , 11 , 12 ]. …

Current State of Human Gene Therapy: Approved Products and Vectors.

In the realm of gene therapy, a pivotal moment arrived with Paul Berg's groundbreaking identification of the first recombinant DNA in 1972. This achievement set the stage for future breakthroughs. Conditions once considered undefeatable, like melanoma, pancreatic cancer, and a host of other ailments, are now being addressed at their root cause-the genetic level. Presently, the gene therapy landscape stands adorned with 22 approved in vivo and ex vivo products, including IMLYGIC, LUXTURNA, Zolgensma, Spinraza, Patisiran, and many more. In this comprehensive exploration, we delve into a rich ass