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Marine-Derived Compounds: A New Horizon in Cancer, Renal, and Metabolic Disease Therapeutics.

Marine-derived compounds represent a rich source of structurally diverse molecules with therapeutic potential for cancer, renal disorders, metabolic-associated fatty liver disease (MAFLD), and atherosclerosis. This review systematically evaluates recent advances, highlighting compounds such as Microcolin H, Benzosceptrin C, S14, HN-001, Equisetin, glycosides (e.g., cucumarioside A2-2), ilimaquinone, and Aplidin (plitidepsin). Key mechanisms include autophagy modulation, immune checkpoint inhibition, anti-inflammatory effects, and mitochondrial homeostasis. Novel findings reveal glycosides' dua

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… Translational challenges include addressing batch-to-batch variability in the fucoidan structure [ 160 ] and developing targeted delivery systems, such as fucoidan-Ce6-chloroquine hydrogels functioning as in situ vaccines to combine photodynamic therapy with autophagy inhibition for enhanced tumor immunotherapy …

Ведомые АПРЕЛЬ БКМА/ТАКИ двойные целевые лиганды-наркотики для селективной и мощной терапии множественной миеломы.

Антиген созревания клеток B (BCMA) в значительной степени проявляется в злокачественных плазменных клетках и является идеальной терапевтической целью в множестве миеломы (MM). Однако эффективность лечения, ориентированного на BCMA, часто ограничивается регулированием деградации антигенов и выходом из опухоли. В этой связи мы представляем информацию о разработке двухцелевого лиганда-наркотика (НРС), использующего подпитывающий распространение лиган (АПРИЛ), естественного лиганда как для BCMA, так и для трансмембранового активатора, а также кальция-модулятора и циклофилина лиганда (TACI). Такая

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… The endocytic activity in RPMI8226 cells was significantly attenuated in the presence of clathrin inhibitors (chloroquine, chlorpromazine). …

Pulmonary hypertension and the potential of 'drug' repurposing: A case for African medicinal plants.

AbstractPulmonary hypertension (PH) is a haemodynamic disorder in which elevated blood pressure in the pulmonary circulation is caused by abnormal vascular tone. Despite advances in treatment, PH mortality remains high, and drug repurposing has been proposed as a mitigating approach. This article reviews the studies that have investigated drug repurposing as a viable option for PH. We provide an overview of PH and highlight pharmaceutical drugs with repurposing potential, based on limited evidence of their mechanisms of action. Moreover, studies have demonstrated the benefits of medicinal plan

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… Chloroquine in pulmonary arterial hypertension: A new role for an old drug? Circ Cardiovasc Genet. 2013;6:310–311. doi: 10.1161/CIRCGENETICS.113.000214. 35. Trankle CR, Canada JM, Kadariya D, et al. …

Management of patients with multiple myeloma in the era of COVID-19 pandemic: a consensus paper from the European Myeloma Network (EMN).

Patients with multiple myeloma (MM) seem to be at increased risk for more severe COVID-19 infection and associated complications due to their immunocompromised state, the older age and comorbidities. The European Myeloma Network has provided an expert consensus statement in order to guide therapeutic decisions in the era of the COVID-19 pandemic. Patient education for personal hygiene and social distancing measures, along with treatment individualization, telemedicine and continuous surveillance for early diagnosis of COVID-19 are essential. In countries or local communities where COVID-19 inf

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… Many agents that are being evaluated against SARS-CoV-2, including antivirals, (hydroxy)chloroquine, azithromycin and remdesivir, may have significant interactions with other drugs and may result in significant hepatic, cardiac or renal toxicity [ 18 , 63 , 64 ]. …

Pruritus: an overview. What drives people to scratch an itch?

Pruritus is a common complaint associated with many conditions. It negatively impacts sleep, quality of life, and mortality. Itch is transmitted along both histaminergic and non-histaminergic pathways with a complex interplay between keratinocytes, immune cells and cutaneous neurons. Individuals who present with pruritus should undergo a thorough assessment, especially those over 65 years old, to exclude underlying malignancy. Treatment no longer consists of antihistamines alone. Physicians now have an array of therapies in their armamentarium, to help alleviate this distressing symptom.

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… Fibromyalgia Bullous disorders Bullous pemphigoid Dermatitis herpetiformis Pregnancy associated Drug eruption | Medications (some examples) Opioids Anti-hypertensives (ACE inhibitors, ARB’s, beta-adrenergic blockers, diuretics, calcium channel blockers) Antibiotics Biguanides; Sulphonylurea derivatives Chloroquine …

Targeting mutant p53 in cancer: from mechanistic insights to therapeutic strategies.

The tumor suppressor p53, often referred to as the “guardian of the genome,” is mutated in more than half of human cancers. These mutations have a significant impact on cancer biology and response to therapy. p53 mutations involve a range of changes that interfere with DNA binding, eliminate tumor suppressor functions, and, in many cases, confer dominant-negative or gain-of-function characteristics that actively promote oncogenesis. These mutations are closely linked to poor clinical outcomes and resistance to standard treatments. This review examines the impact of p53 mutations on cancer ther

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… Conversely, autophagy inhibitors such as chloroquine and hydroxychloroquine are being tested in cancer therapies, but their effects on mutant p53 degradation can vary significantly [ 170 , 171 ]. (e) Targeting p53 phosphorylation-dependent degradation . …

Biology of stem cell paradox: a double-edged sword-implications for cancer therapy.

This comprehensive review investigates the complex interactions between oncogenesis and stem cells, underscoring the crucial importance of cancer stem cells (CSCs) in the mechanisms of tumorigenesis, metastatic dissemination, and resistance to therapeutic interventions. CSCs constitute a distinct subset within neoplasms, defined by unique characteristics such as the ability to self-renew, the potential to differentiate into various cellular phenotypes, and an inherent resistance to conventional treatment strategies. It is hypothesized that these properties are regulated by a multitude of signa

Структурное и механистическое профилирование модулятуры Hurr1 vidofludimus позволяет проектировать лиганд на основе структуры.

В центре биомедицинских исследований находится фактор нейрозащиты, связанный с ядерным рецептором 1 (Nurr1, NR4A2) для его многообещающей нейрозащитной роли в болезни Паркинсона, болезни Альцгеймера и множественном склерозе. Его деятельность может контролироваться лигандами, предлагающими доступ к фармакологической модуляции Hurr1. Вместе с тем связующие эпитопы и механизмы молекулярной активации синтетических активаторов Hurr1 по-прежнему остаются труднодостижимыми, но имеют важное значение для продвижения к новым лекарствам лигандов Hurr1. Здесь мы охарактеризовали диссоциацию Hurr1 димера и

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… The antimalarials amodiaquine (AQ) and chloroquine (CQ) were the first validated synthetic Nurr1 agonists 20 , and recently a few other drugs have been discovered as Nurr1 ligands including statins 21 and the clinically studied dihydroorotate dehydrogenase (DHODH) inhibitor vidofludimus 22 , 23 . …

Targeting Metal Ion Homeostasis for Regulated Cell Death-Amplified Tumor Nanomedicine.

Amidst escalating global health challenges, neoplastic diseases remain a predominant cause of morbidity and mortality, exerting complex and far-reaching effects on human health and societal well-being. The advent of precision medicine has ushered in an era of tailored therapeutic strategies, leveraging individual genetic profiles, tumor microenvironmental features, and exogenous factors to redefine oncology care. Central to these advances is the understanding of cell death, a fundamental biological process encompassing both programmed and non-programmed forms. Programmed cell death is orchestr

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… As the tumor progresses, cancer cells may utilize autophagy to obtain energy and metabolites, which helps them survive in nutrient-deprived and hypoxic conditions ( Figure 2B ). 31 Paulo et al suggested that autophagy inhibitors such as chloroquine and hydroxychloroquine, by inhibiting the acidification … Chloroquine and hydroxychloroquine in antitumor therapies based on autophagy-related mechanisms . Pharmacol Res . 2021 ; 168 : 105582 . doi: 10.1016/j.phrs.2021.105582 33775862 35. Wei X , Xie F , Zhou X , et al. Role of pyroptosis in inflammation and cancer . …

The updated landscape of tumor microenvironment and drug repurposing.

Accumulating evidence shows that cellular and acellular components in tumor microenvironment (TME) can reprogram tumor initiation, growth, invasion, metastasis, and response to therapies. Cancer research and treatment have switched from a cancer-centric model to a TME-centric one, considering the increasing significance of TME in cancer biology. Nonetheless, the clinical efficacy of therapeutic strategies targeting TME, especially the specific cells or pathways of TME, remains unsatisfactory. Classifying the chemopathological characteristics of TME and crosstalk among one another can greatly b

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… Endometrial cancer NCT02755844 Active, not recruiting Antiandrogen (enzalutamide, bicalutamide) Prostate cancer NCT02339168 Active, not recruiting NCT02640534 ; NCT02614859 Recruiting Antibiotic (doxycycline) Breast cancer, uterine cancer, HNSCC NCT03076281 Active, not recruiting NCT02874430 Recruiting Chloroquine … NCT02755844 | Active, not recruiting Antiandrogen (enzalutamide, bicalutamide) | Prostate cancer | NCT02339168 | Active, not recruiting NCT02640534 ; NCT02614859 | Recruiting Antibiotic (doxycycline) | Breast cancer, uterine cancer, HNSCC | NCT03076281 | Active, not recruiting NCT02874430 | Recruiting Chloroquine …

Xanthohumol: Mechanistic Actions and Emerging Evidence as a Multi-Target Natural Nutraceutical.

BACKGROUND: Xanthohumol (XN), a prenylated chalcone flavonoid derived from hops (Humulus lupulus), is increasingly recognized as a highly pleiotropic natural compound. OBJECTIVE: We aimed to structure XN's mechanistic hierarchy with emerging translational relevance across disease areas. METHODS: We performed a comprehensive and integrative literature review of XN for its biological and translational effects across cancer, metabolic, neurological, cardiovascular, hepatic, renal, and dermatological disorders. RESULTS: Mechanistically, XN exerts diverse bioactivities by inhibiting major pro-on

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… XN exhibited the strongest antiplasmodial effect among eight tested chalcone derivatives, with IC 50 values of 8.2 ± 0.3 μM for the chloroquine-sensitive poW strain and 24.0 ± 0.8 μM for the multidrug-resistant Dd2 clone [ 52 ]. … IC 50 , half-maximal inhibitory concentration; CQ, chloroquine; ROS, reactive oxygen species; MDBK, Madin–Darby bovine kidney cells; N.A., not available. Down arrow: decrease. Pathogen Group | Species/Strain (Model) | Concentration | Mechanism Highlights | Ref. …

Hepatocellular carcinoma stem cells: the current state of small molecule-based inhibitors.

Hepatocellular carcinoma (HCC) is the most common type of liver cancer, accounting for over 90% of all cases. Patients with advanced-stage HCC are referred to systemic treatment. Although some advances in HCC therapy have been made in recent years, the prognosis for patients remains poor due to drug resistance, tumor relapse, and metastasis, implying that overall survival remains a challenge. Many studies have shown that tumor-initiating stem cells, also known as cancer stem cells (CSCs), play essential roles in tumorigenesis, metastasis, and treatment resistance in HCC and that future cancer

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… Nanoliposomes containing salinomycin and doxorubicin suppressed tumor growth and reduced the proportion of hepatic CSCs in vivo [ 124 ], and liposomes containing salinomycin and chloroquine synergistically eradicated hepatic CSCs [ 125 ]. … Codelivery of salinomycin and chloroquine by liposomes enables synergistic antitumor activity in vitro. Nanomedicine. 2016;11:1831–46. 10.2217/nnm-2016-0125. 126. Wang M, Xie F, Wen X, Chen H, Zhang H, Liu J, et al. …

Food-derived compounds targeting ferroptosis for cancer therapy: from effects to mechanisms.

Ferroptosis is distinctive type programmed cell death. Tumor cells, with their higher iron levels, render them more susceptible to ferroptosis Inducing ferroptosis can activate immune cells, regulate immune evasion, and inhibit the biology activity of cancer cells. Therefore, ferroptosis-induced cancer cell death could become a promising approach for cancer treatment. Dietary compounds are an important source for drug discovery, and there has been an increasing amount of literature on food-derived ferroptosis inducers and their applications in cancer treatment. This review provides an overview

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… TFEB siRNA and chloroquine can block the pharmacological activity of QUE. QUE enhanced expression of TFEB and nuclear transcription of TFEB and induced ferroptosis, thus killing breast cancer cells ( 89 ). … Both the autophagy and subsequent ferroptosis induced by CUR were alleviated by the autophagy inhibitor chloroquine (CQ) and siBeclin1 ( 96 ). Additionally, Xu B and colleagues reported that CUR inhibited NSCLC cell proliferation and angiogenesis while inducing apoptosis and triggering ferroptosis. …

Non-diabetic hypoglycemia: bridging gaps in diagnosis and treatment: a position statement report by the Arabic Association for the Study of Diabetes and Metabolism (AASD).

BACKGROUND: Non-diabetic hypoglycemia presents a substantial diagnostic challenge due to its diverse and often nonspecific symptomatology. The resultant delay in diagnosis can lead to a myriad of misdiagnoses. This misidentification not only prolongs patient suffering but also elevates the risk of severe complications, such as permanent neurologic damage and mortality. Recognizing the clinical nuances of non-diabetic hypoglycemia is paramount for timely and accurate diagnosis, which ultimately enhances patient outcomes and safety. MAIN BODY: A position statement has been formulated by the Ara

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… selective serotonin re-uptake inhibitors (SSRIs) family: (e.g., fluoxetine, sertraline) Mono-Amin Oxidase Inhibitors (MAOIs): (e.g., selegiline, rasagiline) Antipsychotics, lithium and valproate Certain antibiotics (e.g., gatifloxacin, levofloxacin, sulfamethoxazole) Antimalarial drugs (e.g., quinine, chloroquine …

Secondary Neutropenias.

Neutrophils are a critical component of immunity, particularly against bacteria and other pathogens, but also in inflammation and tissue repair. As a consequence, individuals with neutropenia, defined by a reduction in absolute neutrophil counts, exhibit a strong propensity to severe infections that typically present with muted symptoms. Neutropenias encompass a heterogeneous set of disorders, comprising primary neutropenias, in which specific genes are mutated, and the more common secondary neutropenias, which have diverse non-genetic causes. These include hematological and other cancers, inv

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… hydroxyurea, paclitaxel, vinblastine biological agents | ipilimumab, nivolumab, pembrolizumab, rituximab cell-based therapies | CAR-T therapy, HSCT Other drugs | analgesics/NSAIDs | aspirin, diclofenac, ibuprofen, tenoxicam anticonvulsants | carbamazepine, phenytoin, valproate antimicrobials | acyclovir, chloroquine …

Pathogenesis of Oral Toxicities Associated with Targeted Therapy and Immunotherapy.

Targeted therapy and immunotherapy have redefined cancer treatment. While they have enhanced tumor response and improved survival rates in many cancer types, toxicities continue to occur, and these often involve the oral cavity. Broadly reported as "mucositis" or "stomatitis," oral toxicities induced by targeted therapies differ clinically and mechanistically from those associated with conventional chemotherapy. Manifesting primarily as mucosal lesions, salivary gland hypofunction, or orofacial neuropathies, these oral toxicities may nonetheless lead to significant morbidity and impact patient

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… This may be due to a metabolite of the drug chelating iron and melanin, as with the action of other drugs (e.g., minocycline and chloroquine). …

Growth inhibition of head and neck squamous cell carcinoma cells by sgRNA targeting the cyclin D1 mRNA based on TRUE gene silencing.

Head and neck squamous cell carcinoma (HNSCC) exhibits increased expression of cyclin D1 (CCND1). Previous studies have shown a correlation between poor prognosis of HNSCC and cyclin D1 overexpression. tRNase ZL-utilizing efficacious gene silencing (TRUE gene silencing) is one of the RNA-mediated gene expression control technologies that have therapeutic potential. This technology is based on a unique enzymatic property of mammalian tRNase ZL, which is that it can cleave any target RNA at any desired site by recognizing a pre-tRNA-like complex formed between the target RNA and an artificial sm

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… Our previous studies also suggest that functional uptake of sgRNA is mediated by an intracellular vesicular transport process, since cellular responses induced by sgRNA are blocked by chloroquine and brefeldin A (Tamura et al., submitted, unpublished data). …

Stat1 activation attenuates IL-6 induced Stat3 activity but does not alter apoptosis sensitivity in multiple myeloma.

BackgroundMultiple myeloma (MM) is at present an incurable malignancy, characterized by apoptosis-resistant tumor cells. Interferon (IFN) treatment sensitizes MM cells to Fas-induced apoptosis and is associated with an increased activation of Signal transducer and activator of transcription (Stat)1. The role of Stat1 in MM has not been elucidated, but Stat1 has in several studies been ascribed a pro-apoptotic role. Conversely, IL-6 induction of Stat3 is known to confer resistance to apoptosis in MM.MethodsTo delineate the role of Stat1 in IFN mediated sensitization to apoptosis, sub-lines of t

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… Chloroquine disphosphate was added 30 minutes before transfection to the cell culture plates. DNA (10 μg) was mixed with 0.25 M CaCl 2 . The mixture was then added to an equal volume of 2x HEPES-buffered saline, incubated for 20 minutes and finally added to the cells. …

A systematic review of ongoing clinical trials in optic pathway gliomas.

INTRODUCTION: Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of OPGs within the optic pathway typically precludes complete resection or optimal radiation dosing, hence outcomes remain poor compared to many other low-grade gliomas. The aim of this systematic review was to formulate a comprehensive list of all current ongoing clinical trials that are specifically looking at clinical care of OPGs in order t

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… Re-purposing chloroquine for glioblastoma: potential merits and confounding variables. Front Oncol. 2018;8:335. doi: 10.3389/fonc.2018.00335. 56. Krueger DA, Care MM, Holland K, et al. Everolimus for subependymal giant-cell astrocytomas in tuberous sclerosis. …

Targeting Autophagy with Natural Products as a Potential Therapeutic Approach for Cancer.

Macro-autophagy (autophagy) is a highly conserved eukaryotic intracellular process of self-digestion caused by lysosomes on demand, which is upregulated as a survival strategy upon exposure to various stressors, such as metabolic insults, cytotoxic drugs, and alcohol abuse. Paradoxically, autophagy dysfunction also contributes to cancer and aging. It is well known that regulating autophagy by targeting specific regulatory molecules in its machinery can modulate multiple disease processes. Therefore, autophagy represents a significant pharmacological target for drug development and therapeutic