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Advances and Challenges in Cancer Stem Cells for Onco-Therapeutics.

Six decades have passed since the foundational recognition of the primary properties of the stem cells. Research on stem cells has since remained at the forefront of efforts to combat a spectrum of diseases, most notably cancer. Despite remarkable progress in medical science, a definitive cure for cancer has remained elusive, spurring the pursuit of diverse therapeutic strategies, among which stem cell therapy is a particularly promising avenue. Moreover, the utilization of cancer stem cells as a therapeutic source holds immense potential for addressing intractable diseases. The strategy of ta

Targeting the Cancer-Neuronal Crosstalk in the Pancreatic Cancer Microenvironment.

Pancreatic ductal adenocarcinoma (PDAC) represents one of the most aggressive solid tumors with a dismal prognosis and an increasing incidence. At the time of diagnosis, more than 85% of patients are in an unresectable stage. For these patients, chemotherapy can prolong survival by only a few months. Unfortunately, in recent decades, no groundbreaking therapies have emerged for PDAC, thus raising the question of how to identify novel therapeutic druggable targets to improve prognosis. Recently, the tumor microenvironment and especially its neural component has gained increasing interest in the

Long non-coding RNA LINC00968 attenuates drug resistance of breast cancer cells through inhibiting the Wnt2/β-catenin signaling pathway by regulating WNT2.

BackgroundBreast cancer is one the most common cancers, making it the second leading cause of cancer-related death among women. Long non-coding RNAs (lncRNAs), with tightly regulated expression patterns, also serve as tumor suppressor during tumorigenesis. The present study aimed to elucidate the role of LINC00968 in breast cancer via WNT2-mediated Wnt2/β-catenin signaling pathway.MethodsBreast cancer chip GSE26910 was utilized to identify differential expression in LINC00968 and WNT2. The possible relationship among LINC00968, transcriptional repressor HEY and WNT2 was analyzed and then verif

Dendrimer-doxorubicin conjugates exhibit improved anticancer activity and reduce doxorubicin-induced cardiotoxicity in a murine hepatocellular carcinoma model.

Hepatocellular carcinoma (HCC) is the 2nd leading cause of cancer-related deaths every year globally. The most common form of treatment, hepatic arterial infusion (HAI), involves the direct injection of doxorubicin (DOX) into the hepatic artery. It is plagued with limited therapeutic efficacy and the occurrence of severe toxicities (e.g. cardiotoxicity). We aim to improve the therapeutic index of DOX delivered via HAI by loading the drug onto generation 5 (G5) poly(amidoamine) (PAMAM) dendrimers targeted to hepatic cancer cells via N-acetylgalactosamine (NAcGal) ligands. DOX is attached to the

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… After sonication for 20 minutes, P1 and P2 conjugates were sterile-filtered through syringe filters with a pore size of 800 nm and warmed to 37°C before measurements. …

Изменчивость генотипов кассавы (Manihot Escelenta [Cranz]) для состава питания в юго-западной Эфиопии.

В ходе исследования было использовано в общей сложности 100 Генотипы кассавы, полученные из МИТА, Нигерия (биофортифицированные генотипы), и собранные на месте земли Эфиопии, сохранены в Центре сельскохозяйственных исследований Джиммы. Таким образом, понимание изменчивости состава рациона питания может служить ориентиром для будущего генетического совершенствования и поддерживать развитие питательных разновидностей маниоки. Цель этого исследования заключалась в оценке изменчивости генотипов кассавы на основе их анализа состава питательных веществ. Анализ различий (АНОВА) выявил весьма значител

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… For the analysis, 1 g of dried sample was weighed using a sensitive balance and extracted using 80% methanol by sonication for 30 min. The solvent was centrifuged and filtered using 0.45 μm membrane. Gradient elution was carried out at 90% A / 10% B, increasing B to 50% over 30 min. …

Brevilin A reverses colitis of inflammatory bowel disease via modulation of TNF-α signaling and microbiome dysregulation.

BackgroundBrevilin A (Br) has shown potential in modulating inflammatory bowel disease (IBD). Our study aims to explore its mechanism of anti-inflammatory action.MethodsColitis was induced in C57BL/6 mice with dextran sulfate sodium (DSS), followed by treatment with or without Br(20 mg/kg). Fecal microbiota and metabolites were profiled by metagenomic sequencing and liquid chromatography-mass spectrometry (LC-MS), respectively. Furthermore, to delineate the essential role of the gut microbiota, we employed antibiotic-treated (microbiota-depleted) mice in our investigation of Br's mechanism of

LAMP5 modulates IRF4 stability and nuclear transport: a critical mechanism in myeloma progression and therapy.

Multiple myeloma is a malignant hematopoietic neoplasm characterized by unclear molecular mechanisms and lack of highly effective targeted therapies for clinical application. Interferon regulatory factor 4 (IRF4) is a well-known core transcription factor that regulates the progression of myeloma, but the molecular mechanisms underlying its protein homeostasis regulation are unknown. Our research shows that lysosomal-associated membrane protein 5 (LAMP5) interacts with IRF4 and prevents its degradation through the autophagy-lysosome pathway, thereby facilitating the progression of myeloma. Addi

Maintenance therapy for AML after allogeneic HCT.

Allogeneic hematopoietic cell transplant (allo-HCT) for eligible patients with acute myeloid leukemia (AML) in first complete remission is a central treatment paradigm to achieve durable remission. However, disease relapse after allo-HCT remains a significant concern and generally portends a poor prognosis. There is significant interest regarding the role for maintenance therapy after allo-HCT for patients with high risk of relapse, regardless of the presence of measurable residual disease. While there are currently no therapies approved for maintenance therapy for AML after allo-HCT, there ar

RSK inhibitor BI-D1870 inhibits acute myeloid leukemia cell proliferation by targeting mitotic exit.

The 90 kDa Ribosomal S6 Kinase (RSK) drives cell proliferation and survival in cancers, although its oncogenic mechanism has not been well characterized. Phosphorylated level of RSK (T573) was increased in acute myeloid leukemia (AML) patients and associated with poor survival. To examine the role of RSK in AML, we analyzed apoptosis and the cell cycle profile following treatment with BI-D1870, a potent inhibitor of RSK. BI-D1870 treatment increased the G2/M population and induced apoptosis in AML cell lines and patient AML cells. Characterization of mitotic phases showed that the metaphase/an

Repurposing Drugs for Acute Myeloid Leukemia: A Worthy Cause or a Futile Pursuit?

Acute myeloid leukemia (AML) is a clinically and genetically heterogenous malignancy of myeloid progenitor cells that affects patients of all ages. Despite decades of research and improvement in overall outcomes, standard therapy remains ineffective for certain subtypes of AML. Current treatment is intensive and leads to a number of secondary effects with varying results by patient population. Due to the high cost of discovery and an unmet need for new targeted therapies that are well tolerated, alternative drug development strategies have become increasingly attractive. Repurposing existing d

Enhanced Antitumor Activity and Induction of Immunogenic Cell Death in NUT Carcinoma Cells by Combining Oncolytic Viruses with the Dual Inhibitor NEO2734.

NUT carcinoma (NC) is a rare exceptionally aggressive malignancy, defined by NUTM1 gene translocations, most commonly generating a BRD4::NUTM1 fusion that results in a poor prognosis and limited therapeutic options. Oncolytic virotherapy has emerged as a promising strategy for NC, and the dual bromodomain and extra-terminal domain (BET) and p300/CBP inhibitor NEO2734 has demonstrated potent antiproliferative activity. To investigate multimodal therapeutic approaches that combine epigenetic modulation with immunogenic and cytotoxic effects of oncolytic viruses (OVs), we evaluated two recombinan

Спасение гиппокампальной синаптической пластичности и эффективности памяти Финголимода (FTY720) в модели APP/PS1 болезни Альцгеймера сопровождается коррекцией метаболизма финголипидов, полиаминов и фосфолипидного насыщенного состава.

Ранее, наши метаболомические, транскриптомные и геномные исследования характеризовали путь церамида/шфингомилена как терапевтическую цель в болезни Альцгеймера, и мы показали, что FTY720, фингозин-1-фосфахатный рецептор, утвержденный для лечения множественных склерозов, восстанавливает синаптическая пластичность и память в мышах APP/PS1. Для дальнейшего изучения того, как FTY720 спасает патологию, мы провели метаболический анализ мозга, плазмы и печени обученных APP/PS1 и диких мышей. APP/PS1 мыши продемонстрировали локальные нарушения мозга в полиаминах, фосфолипидах и сфинголипидах. Большинс

Targeted Drug Delivery in Periorbital Non-Melanocytic Skin Malignancies.

Targeted drug delivery has emerged as a transformative approach in the treatment of periorbital skin malignancies, offering the potential for enhanced efficacy and reduced side effects compared to traditional therapies. This review provides a comprehensive overview of targeted therapies in the context of periorbital malignancies, including basal cell carcinoma, squamous cell carcinoma, sebaceous gland carcinoma, and Merkel cell carcinoma. It explores the mechanisms of action for various targeted therapies, such as monoclonal antibodies, small molecule inhibitors, and immunotherapies, and their

Углубленный анализ антител сыворотки против белков жизненного цикла вируса Эпштейн-Барр и EBNA1, ANO2, GlialCAM и CRYAB peptides у пациентов с множественным склерозом.

Была установлена тесная связь между множественным склерозом (MS) и вирусом Эпштейн-Барр (EBV), однако точная роль EBV в НР остается спорной. В последнее время в качестве возможного патофизиологического механизма было предложено использовать молекулярную аналогию между EBNA1 и специфической GlialCAM, CRYAB и ANO2. Цель этого исследования состояла в том, чтобы проанализировать антиЭБВ-организмы у пациентов, страдающих ОВБ, на предмет выявления (I) белков жизненного цикла, (II) переносных реактивных пептидов и (III) в ходе лечения.МЕТОДЫ: В этом ретроспективном поперечном исследовании 258 Включен

Nanomedicine: Principles, Properties, and Regulatory Issues.

Several scientific areas have benefited significantly from the introduction of nanotechnology and the respective evolution. This is especially noteworthy in the development of new drug substances and products. This review focuses on the introduction of nanomedicines in the pharmaceutical market, and all the controversy associated to basic concepts related to these nanosystems, and the numerous methodologies applied for enhanced knowledge. Due to the properties conferred by the nanoscale, the challenges for nanotechnology implementation, specifically in the pharmaceutical development of new dru

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… Nanomedicine manufacturing processes, as already mentioned above, compromise top-down and bottom-down approaches, which include multiple steps, like homogenization, sonication, milling, emulsification, and sometimes, the use of organic solvents and further evaporation. …

Drug repurposing in malignant pleural mesothelioma: a breath of fresh air?

Drug repurposing is the use of known drugs for new indications. Malignant pleural mesothelioma (MPM) is a rare cancer with a poor prognosis. So far, few treatments have been approved in this disease. However, its incidence is expected to increase significantly, particularly in developing countries. Consequently, drug repurposing appears as an attractive strategy for drug development in MPM, since the known pharmacology and safety profile based on previous approvals of repurposed drugs allows for faster time-to-market for patients and lower treatment cost. This is critical in low- and middle-in

Unc-51 like kinase 3 (ULK3) contributes to autophagy and cell survival in multiple myeloma.

Despite effective therapies such as proteasome inhibitors, multiple myeloma (MM) patients relapse with refractory disease. Analysis of RNA sequencing data from CD138 + MM patient cells (n = 813) across disease stages identifies an autophagy gene signature. Particularly elevated ULK3 expression is strongly associated with disease progression. Functional studies reveal that ULK3 supports MM cell survival via the ULK-ATG13-FIP200 complex. We generate small-molecule kinase inhibitors (SG3-014/MA9-060) exhibiting nanomolar potency against ULK3, with binding confirmed by co-crystallization. While ex

Emerging therapeutic strategies in glioblastsoma: drug repurposing, mechanisms of resistance, precision medicine, and technological innovations.

Glioblastoma (GBM) is an aggressive Grade IV brain tumor with a poor prognosis. It results from genetic mutations, epigenetic changes, and factors within the tumor microenvironment (TME). Traditional treatments like surgery, radiotherapy, and chemotherapy provide limited survival benefits due to the tumor's heterogeneity and resistance mechanisms. This review examines novel approaches for treating GBM, focusing on repurposing existing medications such as antipsychotics, antidepressants, and statins for their potential anti-GBM effects. Advances in molecular profiling, including next-generation

Роль Neuroptide Y в зубной касти: уравновешивание нейрогенного воспаления и модуляции боли.

ВЕЩЕСТВО: Стоматологическая целлюлоза представляет собой густонаселенную, низкосопоставимую ткань, в которой нейронное воспаление может быстро перерасти в отеку, поднимает внутрипульсовое давление, микроваскулярный компромисс и боль. В то время как пептид вещества P (SP) и кальцитонин (CGRP) являются хорошо зарекомендовавшими себя движущими силами вазодиляции целлюлозы, внутренний контррегулятивный механизм Neuroopepide Y (NPY) остается относительно недостаточно изученным.ЦЕЛИ: Критически синтезировать текущие данные по NPY в области стоматологической биологии целлюлозы с уделением особого вни

Липидированные мезофорные наночастицы, нагруженные тимокиноном, в качестве нового метода лечения аутоиммунного энцефаломиелита у крыс.

AIMS: Пересечение мозгового барьера (BBB) по-прежнему является серьезной проблемой для доставки терапевтических агентов в центральную нервную систему. Цель этого исследования состояла в том, чтобы оценить потенциал новых наноформуляционных силикатных силиканочастиц (MSN), покрытых липидным двуслойным слоем (LB), с тем чтобы повысить уровень доставки и потенциальное ремиелионирующее воздействие тимокинона (TQ). МЕТОДЫ: Составы характеризовались микроскопией передачи электронов и динамическим рассеиванием света для определения потенциала зета и размера частиц. Экспериментальная аутоиммунная энце