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Enhancing the Bioavailability of Resveratrol: Combine It, Derivatize It, or Encapsulate It?

Overcoming the limited bioavailability and extensive metabolism of effective in vitro drugs remains a challenge that limits the translation of promising drugs into clinical trials. Resveratrol, despite its well-reported therapeutic benefits, is not metabolically stable and thus has not been utilized as an effective clinical drug. This is because it needs to be consumed in large amounts to overcome the burdens of bioavailability and conversion into less effective metabolites. Herein, we summarize the more relevant approaches to modify resveratrol, aiming to increase its biological and therapeut

Transcriptomic profiling identifies ferroptosis and NF-κB signaling involved in α-dimorphecolic acid regulation of microglial inflammation.

BACKGROUND: Microglia-evoked neuroinflammation contributes to neurodegenerative diseases such as multiple sclerosis (MS). Metabolic reprogramming, including changes in polyunsaturated fatty acids (PUFAs), plays a critical role in MS pathophysiology. Previous studies identified reduced plasma α-dimorphecolic acid (α-DIPA), a linoleic acid derivative, in MS patients. This study investigated the anti-inflammatory effects of α-DIPA on microglia and the underlying pathways. METHODS: Lipopolysaccharide (LPS)-induced BV-2 microglial inflammation was used as an in vitro model. α-DIPA effects were ass

Roles of LINC01473 and CD74 in osteoblasts in multiple myeloma bone disease.

The suppression of osteoblast (OB) activity is partially responsible for multiple myeloma (MM) bone disease. Long non-coding RNAs (lncRNAs) play a vital role in bone formation and resorption. However, their functions in OBs from patients with MM have rarely been reported. Through high-throughput sequencing of OBs from patients with MM and healthy controls, we identified several lncRNAs and messenger RNAs (mRNAs) with different expression profile and validated them using quantitative real-time PCR. In total, 22 upregulated and 21 downregulated lncRNAs were found in OBs from patients with MM. Mo

Дисфункция мозгового барьера (BBB) в заболеваниях CNS: уделение внимания перицитам.

Дизфункция мозгового барьера (BBB) является важным патологическим механизмом в заболеваниях центральной нервной системы (CNS) и может вызвать ряд патологических реакций, таких, как нейроинфламмационная реакция, окислительный стресс, иммунная инфильтрация и т.д., что усугубляет повреждение мозга. Вместе с тем исследователи часто игнорируют перициты, и ни одно обзорное исследование пока еще не подытожило механизм, с помощью которого перициты способствуют дисфункции ББД в заболеваниях КНС.Поэтому в настоящем обзоре изучается патофизиология дисфункции ББД в связи с заболеваниями КНС и содержится п

MicroRNAs and long non-coding RNAs in pancreatic cancer: From epigenetics to potential clinical applications.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) are two relevant classes of non-coding RNAs (ncRNAs) that play a pivotal role in a number of molecular processes through different epigenetic regulatory mechanisms of gene expression. As a matter of fact, the altered expression of these types of RNAs leads to the development and progression of a varied range of multifactorial human diseases. Several recent reports elucidated that miRNA and lncRNAs have been implicated in pancreatic cancer (PC). For instance, dysregulation of such ncRNAs has been found to be associated with chemoresistance,

PROTACs: great opportunities for academia and industry (an update from 2020 to 2021).

PROteolysis TArgeting Chimeras (PROTACs) technology is a new protein-degradation strategy that has emerged in recent years. It uses bifunctional small molecules to induce the ubiquitination and degradation of target proteins through the ubiquitin-proteasome system. PROTACs can not only be used as potential clinical treatments for diseases such as cancer, immune disorders, viral infections, and neurodegenerative diseases, but also provide unique chemical knockdown tools for biological research in a catalytic, reversible, and rapid manner. In 2019, our group published a review article "PROTACs:

Convergent targeting of FUNDC1-dependent mitophagy sensitises and overcomes resistance to EGFR inhibition.

Combination therapies are critical for enhancing and prolonging the efficacy of EGFR inhibitors. Here, we uncover FUNDC1-dependent mitophagy as a key protective mechanism in EGFR-mutant non-small cell lung cancer (NSCLC). We discover that nitidine, a bioactive component of the traditional Xihuang Pill formulation, synergises with the EGFR inhibitor osimertinib. Mechanistically, nitidine and osimertinib synergistically disrupt FUNDC1-mediated mitophagy, leading to mitochondrial dysfunction and accumulation of reactive oxygen species in EGFR-mutant NSCLC. We further show that both osimertinib an

Nanoparticle Strategies for Bone Metastasis Immunotherapy: Targeting, Immune Reprogramming and Combination Therapy.

Bone metastases remain one of the most clinically devastating complications of advanced cancer, particularly in breast, prostate, and lung malignancies, where they drive pain, fractures, hypercalcemia, and progressive functional decline. Their management is further complicated by a highly immunosuppressive bone microenvironment characterized by osteoclast-driven bone destruction, myeloid cell dominance, impaired antigen presentation, and weak effector T-cell infiltration, all of which limit the activity of conventional immunotherapies. In this setting, nanoparticles are emerging not merely as

Epigenetic regulation in gynecological cancers: a paradigm shift in immunotherapy strategies.

Recent advances in immunotherapy have transformed the therapeutic landscape of gynecological cancers; however, durable responses remain limited by tumor heterogeneity and immune evasion mechanisms. Emerging evidence highlights epigenetic modifications comprising of DNA methylation, histone modifications, and RNA methylation as pivotal regulators of the tumor immune microenvironment and immunotherapy efficacy. This review comprehensively explores how these epigenetic alterations modulate immune cell infiltration, antigen presentation, immune checkpoint expression, and tumor immunogenicity acros

Совпадение в полном тексте источника
… Over 170 RNA modifications have been documented, with m6A and m1A being particularly influential due to their effects on RNA stability, translation, and interactions with cellular machinery. …

Nanomedicine Approaches for Autophagy Modulation in Cancer Therapy.

Cancer is a daunting global health problem with a steadily rising incidence. Despite the wide arsenal of current anticancer therapies, challenges such as drug resistance, tumor heterogeneity, poor targeting, and severe side effects often lead to suboptimal efficacy and poor patient outcomes, highlighting the need for innovative therapies. Autophagy modulation has emerged as an attractive approach to complement existing therapies. The dual role of autophagy in cancer promotion and suppression has inspired the development of new drugs and therapeutic strategies focusing on both inhibition and in

Emerging Roles of Mesenchymal Stem/Stromal-Cell-Derived Extracellular Vesicles in Cancer Therapy.

Despite the tremendous efforts of many researchers and clinicians, cancer remains the second leading cause of mortality worldwide. Mesenchymal stem/stromal cells (MSCs) are multipotent cells residing in numerous human tissues and presenting unique biological properties, such as low immunogenicity, powerful immunomodulatory and immunosuppressive capabilities, and, in particular, homing abilities. Therapeutic functions of MSCs are mediated mostly by the paracrine effect of released functional molecules and other variable components, and among them the MSC-derived extracellular vesicles (MSC-EVs)

In vitro and in vivo activity of a novel locked nucleic acid (LNA)-inhibitor-miR-221 against multiple myeloma cells.

Background & aimThe miR-221/222 cluster is upregulated in malignant plasma cells from multiple myeloma (MM) patients harboring the t(4;14) translocation. We previously reported that silencing of miR-221/222 by an antisense oligonucleotide induces anti-MM activity and upregulates canonical miR-221/222 targets. The in vivo anti-tumor activity occurred when miR-221/222 inhibitors were delivered directly into MM xenografts. The aim of the present study was to evaluate the anti-MM activity of a novel phosphorothioate modified backbone 13-mer locked nucleic acid (LNA)-Inhibitor-miR-221 (LNA-i-miR-22

Enhanced prognostic signature for lung adenocarcinoma through integration of adjacent normal and tumor gene expressions.

BackgroundCancer prognosis-related signatures have traditionally been constructed based on gene expression profiles derived from tumor or normal tissues. However, the potential benefits of incorporating gene expression profiles from both tumor and normal tissues to improve signature performance have not been explored.MethodsIn this study, we developed three prognostic models for lung adenocarcinoma (LUAD) using gene expression profiles from tumor tissues, normal tissues, and a combination (COM) of both, sourced from The Cancer Genome Atlas (TCGA). To ensure comparability, the same workflow was

Blocking the MIF-CD74 axis augments radiotherapy efficacy for brain metastasis in NSCLC via synergistically promoting microglia M1 polarization.

BackgroundBrain metastasis is one of the main causes of recurrence and death in non-small cell lung cancer (NSCLC). Although radiotherapy is the main local therapy for brain metastasis, it is inevitable that some cancer cells become resistant to radiation. Microglia, as macrophages colonized in the brain, play an important role in the tumor microenvironment. Radiotherapy could activate microglia to polarize into both the M1 and M2 phenotypes. Therefore, searching for crosstalk molecules within the microenvironment that can specifically regulate the polarization of microglia is a potential stra

Sodium Selenite Regulates the Proliferation and Apoptosis of Gastric Cancer Cells by Suppressing the Expression of LncRNA HOXB-AS1.

Gastric carcinoma has a high incidence, accounting for approximately 6% of all cancers worldwide. The in vivo antitumor effect of sodium selenite on gastric carcinoma has been demonstrated. This study therefore aimed to further explore its targets in gastric cancer in vitro and elucidate its mechanism of action. The effects of inorganic sodium selenite (Na2SeO3) on apoptosis, proliferation, and invasion of gastric cancer cells were investigated, and the interaction between Na2SeO3 and expression of long noncoding RNA homeobox B cluster antisense RNA 1 (HOXB-AS1) was investigated to elucidate t

Aminoquinolines as Translational Models for Drug Repurposing: Anticancer Adjuvant Properties and Toxicokinetic-Related Features.

The indiscriminate consumption of antimalarials against coronavirus disease-2019 emphasizes the longstanding clinical weapons of medicines. In this work, we conducted a review on the antitumor mechanisms of aminoquinolines, focusing on the responses and differences of tumor histological tissues and toxicity related to pharmacokinetics. This well-defined analysis shows similar mechanistic forms triggered by aminoquinolines in different histological tumor tissues and under coexposure conditions, although different pharmacological potencies also occur. These molecules are lysosomotropic amines th

Изучение механизма Shengmai San для лечения аденокарциномы легких на основе биоинформатики и моделирования молекулярной динамики.

Изучение механизма Shengmai San (SMS) в лечении аденокарциномы легких (LUAD) на основе комплексной стратегии, сочетающей «сетевую фармакологию, биоинформатику, стыковку молекулярной стыковки и моделирование молекулярной динамики», в целях разработки точной стратегии комбинированной терапии и выявления потенциальных биоактивных соединений. Дифференцированные гены в LUAD были выявлены в базе данных Gene Express Omnibus с использованием R (первоначально разработанные в Bell Laboratories и в настоящее время управляемые Lucent Technologies). Из энциклопедии традиционной китайской медицины были извл

A novel approach to enhance glioblastoma multiforme treatment efficacy: non-coding RNA targeted therapy and adjuvant approaches.

BackgroundGlioblastoma multiforme (GBM) is a lethal brain tumor. With the current gold standard chemotherapy treatment, temozolomide (TMZ), many patients do not survive beyond one year. While the urgency of researching novel treatments is understandable, the prohibitively high costs and the prolonged duration of research and clinical trials significantly delay the availability of medical advancements to the general public. This highlights the urgent need for adjuvant therapies to enhance treatment effectiveness.Main bodyRecent research has suggested the potential of repurposing FDA-approved dr

Перепрофилированный активатор Nrf2 диметилфумарат спасает мышцы воспаление и фиброз в отягченной мышиной модели мышечной дистрофии Дученна.

В унаследованных нейромускульных болезнях мышечная дистрофия Дюченна (ДМД) глюкокортикоиды значительно медленнее прогрессируют, но в то же время создают достаточно серьезные побочные эффекты, исключающие применение в значительной части пациентов. Распространяя наши выводы о том, что в результате острого лечения с УЛХ были одобрены многочисленные склерозные препараты, диметилфумарат (ДМФ), спасающая мышечную патологию у молодых мышей Mdx, мы намеревались провести доклиническое тестирование на перевод. Чтобы усилить фенотип болезни у взрослых мышц mdx, у которых обычно нет эквивалентной человече

Нацеливаюсь на иммунологический синапс в нескольких миэломах.

Иммунологический синапс, высокоорганизованный соединитель клеток, является важной основой для эффективного убийства раковых клеток с помощью Т. Однако в миеломе терапевтическое сопротивление отражает множество взаимодействующих слоев, включая синаптическое нарушение, клональную эволюцию, метаболическую перепрограммирование и пространственные неоднородные ниши костного мозга, которые могут способствовать дисфункции Т-клеток и иммунной отток. В этом обзоре иммунологический синапс в качестве потенциально изменяемого межклеточного интерфейса: мы описываем, как ниша костного мозга влияет на синапти