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Mechanisms of thrombin-induced MAPK activation associated with cell proliferation in human cultured tracheal smooth muscle cells.

The elevated level of thrombin has been detected in the airway fluids of asthmatic patients. However, the implication of thrombin in the pathogenesis of bronchial hyperreactivity was not completely understood. Therefore, in this study we investigated the effect of thrombin on cell proliferation and p42/p44 mitogen-activated protein kinase (MAPK) activation in human tracheal smooth muscle cells (TSMCs). Thrombin stimulated [3H]thymidine incorporation and p42/p44 MAPK phosphorylation in a time- and concentration-dependent manner in TSMCs. Pretreatment of TSMCs with pertussis toxin (PTX) signific

A pre-in vitro maturation medium containing cumulus oocyte complex ligand-receptor signaling molecules maintains meiotic arrest, supports the cumulus oocyte complex and improves oocyte developmental competence.

STUDY QUESTION: Can a pre-in vitro maturation (pre-IVM) medium containing signaling molecules rather than chemical/pharmaceutical agents, sustain meiotic arrest and improve developmental competence of in vitro matured oocytes in CF1 outbred mice? SUMMARY ANSWER: A short 2 h period of pre-IVM prevents spontaneous meiotic resumption, improves mitochondria activity in subsequently matured oocytes, and increases developmental competence, pregnancy rate and implantation of resulting embryos. WHAT IS KNOWN ALREADY: Spontaneous resumption of meiosis in vitro is detrimental for oocyte developmental

Peptide modification or blocking of CD8, resulting in weak TCR signaling, can activate CTL for Fas- but not perforin-dependent cytotoxicity or cytokine production.

This study describes a form of partial agonism for a CD8+ CTL clone, S15, in which perforin-dependent killing and IFN-gamma production were lost but Fas (APO1 or CD95)-dependent cytotoxicity preserved. Cloned S15 CTL are H-2Kd restricted and specific for a photoreactive derivative of the Plasmodium berghei circumsporozoite peptide PbCS 252-260 (SYIPSAEKI). The presence of a photoactivatable group in the epitope permitted assessment of TCR-ligand binding by TCR photoaffinity labeling. Selective activation of Fas-dependent killing was observed for a peptide-derivative variant containing a modifi

Pathogenic Mechanisms of Myeloma Bone Disease and Possible Roles for NRF2.

Osteolytic bone lesions are one of the central features of multiple myeloma (MM) and lead to bone pain, fractures, decreased quality of life, and decreased survival. Dysfunction of the osteoclast (OC)/osteoblast (OB) axis plays a key role in the development of myeloma-associated osteolytic lesions. Many signaling pathways and factors are associated with myeloma bone diseases (MBDs), including the RANKL/OPG and NF-κB pathways. NRF2, a master regulator of inflammatory signaling, might play a role in the regulation of bone metabolism via anti-inflammatory signaling and decreased reactive oxygen s

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

Роль и функции " Ирисина " : перспективы последних изменений и неевродегенеративных заболеваний.

Irisin — пептид, полученный из фибронектина типа III, содержащего домен белка 5 (FNDC5) и производимый главным образом мышечными волокнами в соответствии с регулированием пероксисомных прорациатрированных рецепторов гамма-коативатора 1-альфа (PGC1α) во время упражнения. Ирисин стал объектом обширных исследований в силу его потенциала как метаболического регулятора и его антиоксидантных свойств. В частности, она связана с защитными действиями в мозгу. Несмотря на растущий интерес, остается много вопросов относительно молекулярных механизмов, лежащих в основе их воздействия. В настоящем обзоре р

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

Activation of type I protein kinase A during receptor-mediated human T lymphocyte activation.

The experiments reported herein have characterized the signaling pathway leading to stimulation of type I protein kinase A isozyme (PKA-I) activity during the early events of Ag receptor-mediated T cell activation. Inhibitor studies demonstrated that receptor-initiated activation of nonreceptor protein tyrosine kinases, phosphorylation and activation of phospholipase C-gamma 1, and activation of protein kinase C occur temporally and precede PKA-I activation. Bypass of both the TCR/CD3 complex and IL-1R and direct activation of protein kinase C by a phorbol ester can also activate PKA-I. To con

DNA Damaging Drugs

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… Benzoquinone Containing Alkylating Agents Quinones have traditionally represented a major source of anti-cancer compounds 18 . … Triaziquone contains three ethylene imine rings linked to a quinone nucleus. This drug is a substrate for both one-electron and two-electron reducing agents and its cytotoxic activity may result from protein alkylation and oxidative stress. …

Навигация экономического бремени множественной миеломы: понимание экономической эффективности терапии CAR-T и биконкретной антителной терапии.

Цель обзора Multiple mieloma - хроническая злокачественность, и с учетом изменяющихся вариантов лечения понимание экономического бремени и экономической эффективности лечения имеет решающее значение для врачей и исследователей. В этой связи мы рассматриваем недавнее утверждение биконкретных антител и CAR-T для миэломы и их финансовые последствия, включая прямые и косвенные издержки. Мы сравниваем это с нынешними режимами и представляем в настоящем обзоре сопоставление затрат. Мы пришли к выводу о том, что использование более эффективных методов лечения, таких, как CAR-T, в более ранних направл

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… Choon-Quinones M Zelei T Barnett M Beyond medicines’ barriers: exploring the true cost of multiple myeloma J Med Econ 2022 25 1 1167 1175 10.1080/13696998.2022.2133823 36397678 Choon-Quinones M, Zelei T, Barnett M, et al. Beyond medicines’ barriers: exploring the true cost of multiple myeloma. …

Chemotherapy Side-Effects: Not All DNA Damage Is Equal.

Recent advances have increased survival rates of children and adults suffering from cancer thanks to effective anti-cancer therapy, such as chemotherapy. However, during treatment and later in life they are frequently confronted with the severe negative side-effects of their life-saving treatment. The occurrence of numerous features of accelerated aging, seriously affecting quality of life, has now become one of the most pressing problems associated with (pediatric) cancer treatment. Chemotherapies frequently target and damage the DNA, causing mutations or genome instability, a major hallmark

Синергистические механизмы традиционной китайской медицины и протеиновых ингибаторов в многократной терапии миеломы: всеобъемлющий обзор.

Множественная миелома (ММ) — клональная плазменная порча клеток, характеризующаяся инфильтрацией костного мозга, производством моноклонального иммуноглобулина и многосистемным повреждением. Протеозные ингибиторы (ИП), такие, как бортезомиб, карфилзомиб и иксазомиб, значительно улучшили без прогрессии и общее выживание пациентов с ОМ. Однако резистентность к лекарственным препаратам и неблагоприятные последствия, включая периферическую нейропатию и кардиотоксичность, по-прежнему являются основными ограничениями для долгосрочного контроля за заболеваниями. Цель настоящего обзора заключается в вс

Совпадение в полном тексте источника
… Quinones & Terpenoids Celastrol Celastrol, a quinone methide triterpenoid isolated from the root and bark of Tripterygium wilfordii (Thunder God Vine), 48 has emerged as a multi-targeted compound with substantial therapeutic potential in multiple myeloma (MM). … TCM-derived compounds—classified by chemical structure into flavonoids, indole derivatives, terpenoids, quinones, polyphenols, and alkaloids—demonstrate the ability to modulate multiple oncogenic pathways, including PI3K/AKT/mTOR, JAK/STAT3, and NF-κB. …

The metabolites from traditional Chinese medicine targeting ferroptosis for cancer therapy.

Cancer is a major disease with ever-increasing morbidity and mortality. The metabolites derived from traditional Chinese medicine (TCM) have played a significant role in combating cancers with curative efficacy and unique advantages. Ferroptosis, an iron-dependent programmed death characterized by the accumulation of lipid peroxide, stands out from the conventional forms of cell death, such as apoptosis, pyroptosis, necrosis, and autophagy. Recent evidence has demonstrated the potential of TCM metabolites targeting ferroptosis for cancer therapy. We collected and screened related articles publ

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… 200 μg/mL) | Downregulated GPX4 expression | Zhai et al. (2022) Scutellaria barbata | — | Hepatocellular carcinoma | SMMC-7721 (44.26 mg/mL) HepG2 (42.19 mg/mL) and Huh7 cells (52.01 mg/mL) HepG2 and Huh7 cell xenograft models (14 mg/kg/d) | Decreased GPX4 and SLC7A11 expression | Li et al. (2022b) Quinones … Plumbagin increased NAD(P)H quinone dehydrogenase 1 (NQO1) activity and decreased xCT expression, resulting in NQO1-dependent glioma cell death. …

Synergistic induction of apoptosis in human leukemia cells (U937) exposed to bryostatin 1 and the proteasome inhibitor lactacystin involves dysregulation of the PKC/MAPK cascade.

Cotreatment with a minimally toxic concentration of the protein kinase C (PKC) activator (and down-regulator) bryostatin 1 (BRY) induced a marked increase in mitochondrial dysfunction and apoptosis in U937 monocytic leukemia cells exposed to the proteasome inhibitor lactacystin (LC). This effect was blocked by cycloheximide, but not by alpha-amanitin or actinomycin D. Qualitatively similar interactions were observed with other PKC activators (eg, phorbol 12-myristate 13-acetate and mezerein), but not phospholipase C, which does not down-regulate the enzyme. These events were examined in relati

Adjuvant Properties of Caffeic Acid in Cancer Treatment.

Caffeic acid (CA) is a polyphenol belonging to the phenylpropanoid family, commonly found in plants and vegetables. It was first identified by Hlasiwetz in 1867 as a breakdown product of caffetannic acid. CA is biosynthesized from the amino acids tyrosine or phenylalanine through specific enzyme-catalyzed reactions. Extensive research since its discovery has revealed various health benefits associated with CA, including its antioxidant, anti-inflammatory, and anticancer properties. These effects are attributed to its ability to modulate several pathways, such as inhibiting NFkB, STAT3, and ERK

Intracellular Pathways and Mechanisms of Colored Secondary Metabolites in Cancer Therapy.

Despite the great advancements made in cancer treatment, there are still many unsatisfied aspects, such as the wide palette of side effects and the drug resistance. There is an obvious increasing scientific attention towards nature and what it can offer the human race. Natural products can be used to treat many diseases, of which some plant products are currently used to treat cancer. Plants produce secondary metabolites for their signaling mechanisms and natural defense. A variety of plant-derived products have shown promising anticancer properties in vitro and in vivo. Rather than recreating

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… It must be mentioned that topoisomerase II poisons are regularly consumed by humans in their daily diet, such as bioflavonoids (flavones, isoflavones, and flavonols), catechols, catechins, isothiocyanates, and quinones. … Although the parent compound displayed no activity against topoisomerase II, the curcumin quinone oxidation intermediates proved to be potent poisons by disrupting the cell cycle mechanism [ 140 ]. 4.4. …

Воздействие комплексной медицинской помощи на процесс реабилитации пациентов с множественными миеломами в академическом отделении гематологии.

Множественная миелома (ММ) — сложная гематологическая гелингология, часто связанная с осложнениями и проблемами восстановления. Исследования, посвященные конкретным последствиям и факторам, связанным с применением комплексного режима ухода за больными пациентами с множественной миеломой в отделении гематологии, по-прежнему носят ограниченный характер. Изучить положительные аспекты потенциальной пользы всеобъемлющей модели ухода за больными. Сбор клинических данных о пациентах с множественными миеломами, которые с марта проходили обычную химиотерапию в отделении гематологии нашей больницы 2020

Совпадение в полном тексте источника
… For example, Choon-Quinones and others found that the comprehensive nursing model can significantly improve the quality of life of patients with MM and reduce the adverse reactions related to treatment. [ 18 ] However, in China, there are few systematic studies in this field, and there is still a lack … [18] Choon-Quinones M, Zelei T, Németh B, et al. Systematic literature review of health economic models developed for multiple myeloma to support future analyses. J Med Econ. 2023;26:110–9. [19] Chen X, Li D, Liu Y, Zhu L, Jia Y, Gao Y. …

Translation approaches to support systemic anti-cancer therapy consent for individuals with limited English proficiency.

PurposeLimited English proficiency (LEP) is associated with poor cancer outcomes, and written information about systemic anticancer treatment (SACT) is often provided in English only. Unsupervised machine translation of medical information is common, but its effectiveness and accuracy are unclear. This study aimed to (a) compare professional and machine translation of written SACT information and (b) investigate whether providing a bilingual SACT consent form altered comprehension of key information during an interpreted SACT consent consultation.MethodsThis randomised study included healthy,

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… Ray M Kats DJ Moorkens J Rai D Shaar N Quinones D Evaluating a large language model in translating patient instructions to Spanish using a standardized framework JAMA Pediatr 2025 179 9 1026 1033 10.1001/jamapediatrics.2025.1729 40622720 PMC12235533 Ray M, Kats DJ, Moorkens J, Rai D, Shaar N, Quinones …

Melatonin: Facts, Extrapolations and Clinical Trials.

Melatonin is a fascinating molecule that has captured the imagination of many scientists since its discovery in 1958. In recent times, the focus has changed from investigating its natural role as a transducer of biological time for physiological systems to hypothesized roles in virtually all clinical conditions. This goes along with the appearance of extensive literature claiming the (generally) positive benefits of high doses of melatonin in animal models and various clinical situations that would not be receptor-mediated. Based on the assumption that melatonin is safe, high doses have been a

Mechanical Cavity Creation with Curettage and Vacuum Suction (Q-VAC) in Lytic Vertebral Body Lesions with Posterior Wall Dehiscence and Epidural Mass before Cement Augmentation.

Background and Objectives: We describe a novel technique for percutaneous tumor debulking and cavity creation in patients with extensive lytic lesions of the vertebral body including posterior wall dehiscence prior to vertebral augmentation (VA) procedures. The mechanical cavity is created with a combination of curettage and vacuum suction (Q-VAC). Balloon kyphoplasty and vertebral body stenting are used to treat neoplastic vertebral lesions and might reduce the rate of cement leakage, especially in presence of posterior wall dehiscence. However, these techniques could theoretically lead to in

Совпадение в полном тексте источника
… Quinones D. Calvo E. Rossi R.E. Vertebroplasty in the treatment of vertebral tumors: Postprocedural outcome and quality of life Eur. Spine J. 2003 12 356 360 10.1007/s00586-003-0525-z 12687441 PMC3467793 2. Berenson J. Pflugmacher R. Jarzem P. Zonder J. Schechtman K. Tillman J.B. Bastian L. …