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Redefining Chemoresistance: Natural Bioactives as Molecular Modulators at the Cancer-Tumor Microenvironment Interface.

Therapeutic resistance remains a critical barrier in effective cancer treatment, contributing to disease recurrence, progression, and reduced patient survival. In recent years, natural bioactive compounds have emerged as promising adjuncts in oncology due to their ability to modulate multiple biological processes involved in resistance. This review explores current evidence on the role of natural compounds in influencing cancer cell behavior and their interactions with the tumor microenvironment. By organizing these compounds into chemical families, we provide a structured overview of their po

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… Inhibition of mTORC1, via starvation or targeted drugs, releases this complex, initiating autophagosome formation with the help of Vacuolar Protein Sorting 34 and Beclin-1. … Terpenoid | Oridonin [ 236 ] | Cisplatin | Bronchial epithelium cell, tumoral | Apoptosis initiation via activation of autophagosomes through the AMPK/Akt/mTOR signaling pathway. …

Cellular Senescence and Aging: Mechanisms, Disease Convergence, and Therapeutic Frontiers.

Cellular senescence, a stress-induced, irreversible cell cycle arrest coupled with a proinflammatory secretory phenotype, has emerged as both a central driver of aging and a tractable therapeutic target. Although acute senescence contributes beneficially to tumor suppression and wound healing, chronic accumulation of senescent cells sustains systemic inflammaging and accelerates organ dysfunction. This review synthesizes current progress in aging biology into a unified mechanistic and translational framework. We first examine how primary aging hallmarks, such as genomic instability and epigene

Integrating Nature Into Oncology: Enhancing Hematological Malignancies Therapies With Natural Medicine.

Hematological malignancies are complex clonal disorders that pose a significant threat to human health. Current treatment modalities, including radiotherapy, chemotherapy, immunotherapy, and bone marrow transplantation, have demonstrated efficacy but are often limited by side effects, drug resistance, and suboptimal cure rates. Natural medicines, as key elements of complementary and alternative medicine, exhibit considerable potential in combating hematological cancers. Particularly when used in combination with conventional therapies, they can enhance treatment efficacy and reverse drug resis

Potential Therapeutic Benefits of Maintaining Mitochondrial Health in Peripheral Neuropathies.

BackgroundPeripheral neuropathies are a group of diseases characterized by malfunctioning of peripheral nervous system. Neuropathic pain, one of the core manifestations of peripheral neuropathy remains as the most severe disabling condition affecting the social and daily routine life of patients suffering from peripheral neuropathy.MethodThe current review is aimed at unfolding the possible role of mitochondrial dysfunction in peripheral nerve damage and to discuss on the probable therapeutic strategies against neuronal mitotoxicity. The article also highlights the therapeutic significance of

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… Oxidative damage to Atg 4, a key component involved in mitophagy causes impaired autophagosome formation and clearance of damaged mitochondria [ 101 ]. … Such damaged mitochondria undergoes PINK1, PARKIN recruitment mediated ubiquitination and then accumulation in autophagosomes. Healthy parts of mitochondria in turn undergo fusion process using the help of proteins such as OPA1, Mnf 1/2. …

Biomolecular condensates as dynamic regulators of musculoskeletal homeostasis, disease, and therapeutic challenges.

Biomolecular condensates are membraneless assemblies that concentrate proteins, nucleic acids, and other biomolecules into dynamic cellular compartments. Liquid-liquid phase separation (LLPS) is one important route by which such condensates form, particularly when multivalent interactions generate liquid-like, reversible assemblies. However, not every condensate or disease-associated assembly should be explained solely by LLPS. In the musculoskeletal system, condensates have been linked to transcription, signal transduction, RNA metabolism, stress responses, tissue development, homeostasis, an

The prince and the pauper. A tale of anticancer targeted agents.

Cancer rates are set to increase at an alarming rate, from 10 million new cases globally in 2000 to 15 million in 2020. Regarding the pharmacological treatment of cancer, we currently are in the interphase of two treatment eras. The so-called pregenomic therapy which names the traditional cancer drugs, mainly cytotoxic drug types, and post-genomic era-type drugs referring to rationally-based designed. Although there are successful examples of this newer drug discovery approach, most target-specific agents only provide small gains in symptom control and/or survival, whereas others have consiste

Perspectives in Melanoma: meeting report from the Melanoma Bridge (December 1st-3rd, 2022-Naples, Italy).

Outcomes for patients with melanoma have improved over the past decade with the clinical development and approval of immunotherapies targeting immune checkpoint receptors such as programmed death-1 (PD-1), programmed death ligand 1 (PD-L1) or cytotoxic T lymphocyte antigen-4 (CTLA-4). Combinations of these checkpoint therapies with other agents are now being explored to improve outcomes and enhance benefit-risk profiles of treatment. Alternative inhibitory receptors have been identified that may be targeted for anti-tumor immune therapy, such as lymphocyte-activation gene-3 (LAG-3), as have se

HMGB1: новая биомаркировка и лечебная цель аутоиммунной и аутовоспалительной кожных заболеваний.

Вставка 1 группы высокой подвижности (HMGB1) выражена почти во всех человеческих клетках. Во время активации клеток и клеточной смерти нуклеопротеин HMGB1 может перемещаться в внеклеточное пространство, тем самым посредничая ранним подстрекательским ответом как сигнализация или молекулярный рисунок, связанный с повреждением (DAMP). Внешнеклеточный HMGB1 взаимодействует с иммунными клетками, связываясь с системой распознавания рецепторов Toll-подобных (TLR), включая TLR2 и TLR4, и рецептором для современных продуктов для гликации (RAGE), тем самым содействуя иммунной реакции для защиты хоста от

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… In lipopolysaccharide-treated brain microglia, HMGB1 competitively interacts with nucleotide binding oligomerization domain containing 2 (NOD2), thus inducing the formation of autophagosomes ( 25 ). …

[Mechanism of moxibustion at the governor vessel for regulating autophagy against Alzheimer's disease via lncRNA-RP4-mediated Wnt/β-catenin pathway].

OBJECTIVE: To observe the effect of moxibustion at the governor vessel on lncRNA-RP4/miR-939-5p and Bnip3 in APP/PS1 double transgenic mice mediated by Wnt/β-catenin pathway, and to explore the mechanism of moxibustion in the treatment of Alzheimer's disease (AD). METHODS: Sixty 6-month-old APP/PS1 mice were randomly divided into a model group, a rapamycin group, a moxibustion+ 3-methyladenine (3-MA) group and a moxibustion group, with 15 mice in each group. Fifteen C57BL/6J mice of the same age were used as the control group. The rapamycin group was given intraperitoneal injection of rapamyc

Nanoscale insights into hematology: super-resolved imaging on blood cell structure, function, and pathology.

Fluorescence nanoscopy, also known as super-resolution microscopy, has transcended the conventional resolution barriers and enabled visualization of biological samples at nanometric resolutions. A series of super-resolution techniques have been developed and applied to investigate the molecular distribution, organization, and interactions in blood cells, as well as the underlying mechanisms of blood-cell-associated diseases. In this review, we provide an overview of various fluorescence nanoscopy technologies, outlining their current development stage and the challenges they are facing in term

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… Physical and chemical concepts in formation of tetraspanin nanodomain observation on leukocytes - Role of lipid raft boundaries in plasma membrane organization on leukocytes [ 60 ] STORM Non-/activated-states organelles distribution DTS, OCS, microtubules, actin nodules, actin bundles, mitochondria, autophagosomes … Physical and chemical concepts in formation of tetraspanin nanodomain observation on leukocytes - Role of lipid raft boundaries in plasma membrane organization on leukocytes [ 60 ] STORM | Non-/activated-states organelles distribution | DTS, OCS, microtubules, actin nodules, actin bundles, mitochondria, autophagosomes …

Proteasome inhibition by bortezomib parallels a reduction in head and neck cancer cells growth, and an increase in tumor-infiltrating immune cells.

Head and neck cancer (HNC) has frequently an aggressive course for the development of resistance to standard chemotherapy. Thus, the use of innovative therapeutic drugs is being assessed. Bortezomib is a proteasome inhibitor with anticancer effects. In vitro antitumoral activity of Bortezomib was investigated employing human tongue (SCC-15, CAL-27), pharynx (FaDu), salivary gland (A-253) cancer cell lines and a murine cell line (SALTO-5) originated from a salivary gland adenocarcinoma arising in BALB-neuT male mice transgenic for the oncogene neu. Bortezomib inhibited cell proliferation, trigg

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… The activation of the autophagic process can be revealed by the conversion of the cytosolic form LC3-I into the membrane-bound form LC3-II, which is localized in the autophagosomes 37 , 38 . Our results showed that LC3-I and LC3-II were constitutively expressed in DMSO-treated cells. … Bortezomib was shown to stimulate autophagy in HNSCC cells in two studies showing autophagosomes formation, upregulation of LC3-I, -II, Beclin-1 and the JNK-dependent phosphorylation of Bcl-2 after Bortezomib treatment 58 , 59 . …

Исследование новых биомаркеров для нейродегенеративных заболеваний с использованием протеомного анализа и лигандно-объеденных анализов.

ВАЖНЕЙШИЕ/ОБЯЗАТЕЛЬНЫЕ ЦЕЛИ: Нейродегенеративные заболевания являются одной из основных причин заболеваемости и смертности во всем мире, и их бремя в области общественного здравоохранения продолжает расти. Необходимо срочно разработать надежные и чувствительные биомаркеры для содействия своевременной диагностике, мониторингу прогрессии заболеваний и терапевтическому развитию нейродегенеративных расстройств. Протеомные скрининговые стратегии, в том числе антителные микроаррары, являются мощным инструментом для обнаружения биомаркеров, однако их результаты должны быть подтверждены с помощью коли

Gastrointestinal Cancer Therapeutics via Triggering Unfolded Protein Response and Endoplasmic Reticulum Stress by 2-Arylbenzofuran.

Gastrointestinal cancers are a major global health challenge, with high mortality rates. This study investigated the anti-cancer activities of 30 monomers extracted from Morus alba L. (mulberry) against gastrointestinal cancers. Toxicological assessments revealed that most of the compounds, particularly immunotoxicity, exhibit some level of toxicity, but it is generally not life-threatening under normal conditions. Among these components, Sanggenol L, Sanggenon C, Kuwanon H, 3'-Geranyl-3-prenyl-5,7,2',4'-tetrahydroxyflavone, Morusinol, Mulberrin, Moracin P, Kuwanon E, and Kuwanon A demonstrate

Drug Repurposing of Selected Antibiotics: An Emerging Approach in Cancer Drug Discovery.

Drug repurposing is a method of investigating new therapeutic applications for previously approved medications. This repurposing approach to "old" medications is now highly efficient, simple to arrange, and cost-effective and poses little risk of failure in treating a variety of disorders, including cancer. Drug repurposing for cancer therapy is currently a key topic of study. It is a way of exploring recent therapeutic applications for already-existing drugs. Theoretically, the repurposing strategy has various advantages over the recognized challenges of creating new molecular entities, inclu

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… Because ATG5-KO and TP53-KO cells reduced AZM-enhanced cytotoxicity, it became clear that this improved p53 wild-type and the potential to induce apoptosis were to form autophagosomes. 136 AZM was reported to decrease autophagy, which led to a rise in lysosomes and autolysosomes. 129 Therefore, its DOX … Autophagy depletion is indicated by an increase in cytosolic autophagosomes as well as changes in the LC3-II and p62/SQSTM1 autophagy markers. 139 Petroni et al. (2020) examined if the effects of clarithromycin depended on hERG1 and its morphological changes because the drug is known to bind hERG1 K …

An immunotherapeutic approach to decipher the role of long non-coding RNAs in cancer progression, resistance and epigenetic regulation of immune cells.

Immunotherapeutic treatments are gaining attention due to their effective anti-tumor response. Particularly, the revolution of immune checkpoint inhibitors (ICIs) produces promising outcomes for various cancer types. However, the usage of immunotherapy is limited due to its low response rate, suggesting that tumor cells escape the immune surveillance. Rapid advances in transcriptomic profiling have led to recognize immune-related long non-coding RNAs (LncRNAs), as regulators of immune cell-specific gene expression that mediates immune stimulatory as well as suppression of immune response, indi

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… Thus, this review provides a critical analysis of LncRNAs in the regulation of cancer resistance by direct and indirect modification of T cells, B cells, Treg cells, natural killer cells (NKs), macrophages and myeloid-derived suppressor cells (MDSCs), and autophagosomes functionality, projecting it as … HOTAIR not only promotes HLAG expression [ 115 ] to enhance the antigen presentation but also down-regulates CD4 + /CD8 + T-cell subsets, and also involve in autophagosome elongation and closure suggesting the effects of LncRNAs, which needs further studies to understand its mechanisms clearly. …

Antineoplastic effects of CPPTL via the ROS/JNK pathway in acute myeloid leukemia.

Drug resistance and human leukocyte antigen (HLA) matching limit conventional treatment of acute myeloid leukemia (AML). Although several small molecule drugs are clinically used, single drug administration is not sufficient to cure AML, which has a high molecular diversity. Metabolic homeostasis plays a key role in determining cellular fate. Appropriate levels of reactive oxygen species (ROS) maintain the redox system balance, and excessive amounts of ROS cause oxidative damage, thus providing a strategy to eliminate cancer cells. CPPTL is a novel analogue of parthenolide that exhibited signi

Natural bioactive molecules and chemotherapeutics synergism for enhanced cancer therapy.

BACKGROUND: Chemotherapy remains a foundation of cancer care but is limited by multidrug resistance, systemic toxicities, and suboptimal selectivity, prompting interest in adjunctive strategies that improve efficacy and tolerability without adding significant burden to patients or healthcare systems. AIMS/OBJECTIVES: This review highlights evidence on natural bioactive compounds, including polyphenols, alkaloids, terpenoids, and fungal metabolites, as adjuvants to standard chemotherapeutics, with objectives to: first, delineate mechanisms by which these agents enhance cytotoxic efficacy and o

Metabolic crosstalk between stromal and malignant cells in the bone marrow niche.

Bone marrow is the primary site of blood cell production in adults and serves as the source of osteoblasts and osteoclasts that maintain bone homeostasis. The medullary microenvironment is also involved in malignancy, providing a fertile soil for the growth of blood cancers or solid tumors metastasizing to bone. The cellular composition of the bone marrow is highly complex, consisting of hematopoietic stem and progenitor cells, maturing blood cells, skeletal stem cells, osteoblasts, mesenchymal stromal cells, adipocytes, endothelial cells, lymphatic endothelial cells, perivascular cells, and n

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… ALL cells form TnTs with stromal cells in the BM to transfer and exchange mitochondria, autophagosomes, and ICAM-1 ( de Rooij et al., 2017 ). … Tunneling nanotubes facilitate autophagosome transfer in the leukemic niche. Leukemia. 2017;31(7):1651–1654. doi: 10.1038/leu.2017.117. Roshanzamir F., et al. Metastatic triple negative breast cancer adapts its metabolism to destination tissues while retaining key metabolic signatures. Proc. Natl. …

Natural biomolecules and derivatives as anticancer immunomodulatory agents.

Despite advancements in chemotherapy, the issue of resistance and non-responsiveness to many chemotherapeutic drugs that are currently in clinical use still remains. Recently, cancer immunotherapy has gathered attention as a novel treatment against select cancers. Immunomodulation is also emerging as an effective strategy to improve efficacy. Natural phytochemicals, with known anticancer properties, been reported to mediate their effects by modulating both traditional cancer pathways and immunity. The mechanism of phytochemical mediated-immunomodulatory activity may be attributed to the remode

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… Autophagy occurs when microtubule-associated protein 1A/1B-light chain 3 (LC3) is incorporated in pre-autophagosomal membranes, where it is acted upon by autophagy related proteins (ATG) to generate LC3-I, LC3-II and mature autophagosomes ( 99 ). … ACTs increased LC3, LC3-I, LC3-II and autophagosome maturation in cancer cell lines including, but not limited to, leukemia, esophageal, ovarian, pancreatic, and colon. …

Ксантин Оксидореводаза: Меч с двойным отростком в неврологических заболеваниях.

Неинфекционные неврологические расстройства являются второй основной причиной смерти, и их бремя продолжает расти по мере роста и старения населения мира. Окисляющий стресс и воспаление во многом связаны с активацией и развитием множественных склерозов, болезни Альцгеймера, амиотропического бокового склероза, болезни Хантингтона, болезни Паркинсона и даже инсульта. В ходе этого обзора мы изучаем роль деятельности и продуктов " xanthine oxidoreducase " (XOR) во всех вышеупомянутых неврологических заболеваниях. Редоксальный дисбаланс, вызывающий окислительный стресс, может возникнуть и