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Marine Natural Products as Potent Anticancer Agents (2020-2024): Structural Diversity, SARs and Target Prediction.

In recent years, Marine Natural Products (MNPs) have emerged as a significant source for anticancer drug discovery, as many natural products can offer structural diversity, unique mechanisms of action, and relatively low toxicity. This article provides a systematic review of MNPs with reported anticancer activities from 2020 to 2024. These compounds are classified into seven major categories: terpenoids, alkaloids, sterols, polyketides, peptides and proteins, polysaccharides, and macrolides. For each category, we elaborate on the marine sources, structural identification, in vitro anticancer a

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… Activity assays revealed that discorhabdin derivatives A ( 31 ), B ( 32 ), N-13-demethyl U ( 35 ), P ( 37 ), 14-Br-discorhabdin C ( 38 ), L ( 36 ), E ( 39 ), and G/I ( 33 ) exhibited potent cytotoxicity, with mean IC 50 values below 1 μM across six tested cell lines, including MCC13, MCC26, UISO, MKL … For the structural analysis of jezoside B, HRMS determined its molecular formula as C 36 H 57 N 3 O 7 S, identifying it as a similar compound to jezoside with demethylation at C-31. …

Regulation of immunogenic cell death and potential applications in cancer therapy.

Immunogenic cell death (ICD), a type of regulatory cell death, plays an important role in activating the adaptive immune response. Activation of the tumor-specific immune response is accompanied by the cell surface exposure of calreticulin and heat-shock proteins, the secretion of adenosine triphosphate, and the release of high mobility group box-1. In this review, we summarize and classify the latest types of ICD inducers and their molecular mechanisms, and discuss the effects and potential applications of inducing ICD by chemotherapy drugs, targeted drugs, and oncolytic viruses in clinical r

Dual Roles of NIX/BNIP3L in Tumors: Friend or Foe.

Cancer is one of the leading causes of disease-related death worldwide, and targeting key regulatory genes to induce programmed cell death in tumor cells has emerged as a crucial therapeutic strategy, following surgery, radiotherapy, and chemotherapy. As a mitochondrial outer membrane protein, NIX/BNIP3L can both mediate apoptosis to inhibit tumor cell growth and promote tumor cell survival by clearing intracellular reactive oxygen species (ROS) through mitophagy. Therefore, we summarize a brief overview of the structure and function of NIX/BNIP3L, as well as the mechanisms of NIX/BNIP3L gener

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… Zhou S et al. demonstrated that human menstrual blood-derived stem cells (MenSCs) overcome sorafenib resistance in HCC by inducing NIX expression through promoter demethylation. … In summary, demethylation of the NIX promoter may contribute to the treatment of drug-resistant hepatocellular carcinoma. However, NIX-mediated mitophagy promotes the progression of chemoresistance by clearing ROS and facilitating metabolic reprogramming for energy production. …

The Hypoxia-Retinoid Axis in Idiopathic Pulmonary Fibrosis: Multifaceted Etiology and Therapeutic Potential.

Idiopathic pulmonary fibrosis (IPF) is a progressive and lethal lung disease with limited therapeutic options. This review focuses on the role of retinoids, particularly all-trans retinoic acid (atRA), and hypoxia in the pathogenesis of IPF. Despite an established understanding of genetic and environmental factors in IPF, the interplay between retinoid signaling and the response to hypoxia remains poorly explored due to its complexity. Preclinical evidence suggests that atRA could help reduce pulmonary fibrosis by modulating TGF-β signaling pathways and epithelial-to-mesenchymal transition (EM

Histone deacetylase inhibitors for leukemia treatment: current status and future directions.

Leukemia remains a major therapeutic challenge in clinical oncology. Despite significant advancements in treatment modalities, leukemia remains a significant cause of morbidity and mortality worldwide, as the current conventional therapies are accompanied by life-limiting adverse effects and a high risk of disease relapse. Histone deacetylase inhibitors have emerged as a promising group of antineoplastic agents due to their ability to modulate gene expression epigenetically. In this review, we explore these agents, their mechanisms of action, pharmacokinetics, safety and clinical efficacy, mon

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… Recent studies indicate the potential of romidepsin in downregulating DNA methyltransferases, leading to the demethylation of tumor suppressor genes and reactivation of their expression, thereby providing a dual epigenetic therapy approach when combined with DNA methylation inhibitors [ 63 , 64 ]. … Combination treatment of acute myeloid leukemia cells with DNMT and HDAC inhibitors: predominant synergistic gene downregulation associated with gene body demethylation. Leukemia. 2019;33(4):945–56. 10.1038/s41375-018-0293-8. 127. Zhou M, Yuan M, Zhang M, Lei C, Aras O, Zhang X, et al. …

The Ups and Downs of STAT Inhibition in Acute Myeloid Leukemia.

Aberrant Janus kinase-signal transducer and activator of transcription (JAK-STAT) signaling is implicated in the pathogenesis of acute myeloid leukemia (AML), a highly heterogeneous hematopoietic malignancy. The management of AML is complex and despite impressive efforts into better understanding its underlying molecular mechanisms, survival rates in the elderly have not shown a substantial improvement over the past decades. This is particularly due to the heterogeneity of AML and the need for personalized approaches. Due to the crucial role of the deregulated JAK-STAT signaling in AML, select

Targeting aberrant DNA methylation in mesenchymal stromal cells as a treatment for myeloma bone disease.

Multiple myeloma (MM) progression and myeloma-associated bone disease (MBD) are highly dependent on bone marrow mesenchymal stromal cells (MSCs). MM-MSCs exhibit abnormal transcriptomes, suggesting the involvement of epigenetic mechanisms governing their tumor-promoting functions and prolonged osteoblast suppression. Here, we identify widespread DNA methylation alterations of bone marrow-isolated MSCs from distinct MM stages, particularly in Homeobox genes involved in osteogenic differentiation that associate with their aberrant expression. Moreover, these DNA methylation changes are recapitul

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… In this regard, members of the HOX family have been recently described to be key drivers of OB differentiation, in which their expression is fine-tuned by demethylation of their promoters during the osteogenic process 55 . … Yan X 5-Azacytidine improves the osteogenic differentiation potential of aged human adipose-derived mesenchymal stem cells by DNA demethylation PLoS ONE 2014 9 e90846 10.1371/journal.pone.0090846 24603866 PMC3946260 62. …

Decoy cells detected in the urine of a patient with complex karyotype Myelodysplastic neoplasms who underwent umbilical cord blood transplantation: a case report.

BACKGROUND: Currently, few literature reports document cases of decoy cells in the urine of umbilical cord blood transplant patients. The majority of the literature indicates that decoy cells are frequently identified in the urine of kidney transplant recipients. CASE PRESENTATION: This case report describes a patient with Myelodysplastic Neoplasms featuring a complex karyotype who underwent umbilical cord blood transplantation. Postoperative urinary cytology revealed decoy cells, and subsequent BK virus nucleic acid testing was positive. However, the routine use of antiviral drugs by the phy

Starvation-induced long non-coding RNAs are significant for prognosis evaluation of bladder cancer.

BackgroundStarving intratumoral microenvironment prominently alters genic profiles including long non-coding RNAs (lncRNAs), which further regulate bladder cancer (BCa) malignant biological properties, such as invasion and migration.MethodsTranscriptome RNA-sequencing data of 414 BCa tumor tissues and 19 normal tissues were obtained from TCGA database and paired samples of 132 BCa patients. A chain of in vitro validations such as qPCR, migration and invasion assays were performed to reveal the clinical relevance of AC011472.4 and AL157895.1.ResultsA total of 11 lncRNAs were identified as starv

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… Anti-cancer effect of LINC00478 in bladder cancer correlates with KDM1A-dependent MMP9 demethylation. Cell Death Discov. 2022; 8:242. 10.1038/s41420-022-00956-z 31. Huang CS, Ho JY, Chiang JH, Yu CP, Yu DS. …

Evaluation on Efficacy and Safety of Arsenic Trioxide Plus Transcatheter Arterial Chemoembolization Versus Transcatheter Arterial Chemoembolization alone for Unresectable Primary Liver Cancer

Currently, some clinical trials of arsenic trioxide (As203) plus transcatheter arterial chemoembolization (TACE) in the treatment of unresectable primary liver cancer (PLC) had been conducted, but the results were controversial. Therefore, we performed a meta-analysis on 14 clinical trials (1076 cases) to evaluate efficacy and safety of As203 plus TACE versus TACE alone for unresectable PLC. The primary end points included objective response rate (ORR), karnofsky performance score (KPS) improvement rate, and 1-year survival rate. The second end points were adverse events consisting of leukopen

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… et al., 2009); (3) inhibiting proliferation of tumor cell through arresting cell cycle at G1/S or G2/M phase (Huang et al., 2005; Tang et al., 2005; Wang et al., 2008; Zhang et al., 2004); (4) repressing tumor metastasis by down-regulating the expression of CD44 (Liu TF et al., 2001); (5) promoting demethylation …

Keyword Index for Volume 110

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… diffusion-weighted imaging (DWI) 107 diffusion-weighted MRI 616 dihydropyrimidine dehydrogenase 2728 discordance 2195 discrete choice experiment 859 disease control 1721 disease progression 2537 disease subtypes 1088 distant metastasis 1378 DJ-1 (PARK7) 1298 DLBCL 369 DNA damage response 1014 DNA demethylation …

Keyword Index for Volume 90

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… beta-synthase 1969 cystatin C 1961 cytochrome P450 911 cytogenetic analysis 900 cytokines 955, 2312 cytomegalovirus 2149 cytotoxic RNases 270 cytotoxic T lymphocytes 1636 D2 gastrectomy 1727 DCIS 423, 1382 DDC 665 decision aids 333, 2123 definitive chemoradiation 70 deletions 503, 1983 demethylation …

Abstracts from the 13th International Conference for Healthcare and Medical Students (ICHAMS).

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Emerging therapies for autosomal dominant polycystic kidney disease with a focus on cAMP signaling.

Autosomal dominant polycystic kidney disease (ADPKD), with an estimated genetic prevalence between 1:400 and 1:1,000 individuals, is the third most common cause of end stage kidney disease after diabetes mellitus and hypertension. Over the last 3 decades there has been great progress in understanding its pathogenesis. This allows the stratification of therapeutic targets into four levels, gene mutation and polycystin disruption, proximal mechanisms directly caused by disruption of polycystin function, downstream regulatory and signaling pathways, and non-specific pathophysiologic processes sha

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… TET proteins are Fe(II)-dependent and 2-oxoglutarate-dependent methylcytosine dioxygenases. 5hmC acts as an intermediate in the reaction of DNA demethylation or a signal for chromatin factors ( Guibert and Weber, 2013 ). cAMP treatment increased the generation of 5hmC in multiple cell types ( Camarena … In addition to cAMP/PKA targeted transcription factors, cAMP modulates transcriptome by promoting DNA demethylation. DNA hydroxymethylation and demethylation have not been investigated in ADPKD. …

Различия между мужчинами и женщинами-неврофилами, в отношении которых в полиомиках присутствуют РНК.

КОЛИЧЕСТВО: Мужчины и женщины демонстрируют различия в распространенности связанных с нейтрофильом заболеваний, таких, как системная волчанка, эритематос, ревматоидный артрит и множественный склероз, а также различия в нейтрофильных физиологических реакциях, таких, как реакция на инфекцию, повреждение тканей и химотактические факторы. Однако мало что известно об основах различий по признаку пола среди нейтрофилов. МЕТОДЫ: Начиная с людей, нейтрофилов от здоровых доноров, мы использовали RNA-seq для изучения общих профилей RNA, RNA, не связанных с рибосом и, следовательно, не переведенных, RNA

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… These mRNAs were enriched for ribosome proteins, histone H4 lysine 20 (K20) demethylation, and respiratory burst ( Table S3 , Tab 9 ) 31 . The 7 transcripts present in females included a mitochondrial pseudogene, and 6 mRNAs including myosin heavy chain 9 (MYH9). …

Harnessing Epigenetic Mechanisms to Overcome Immune Evasion in Cancer: The Current Strategies and Future Directions.

Combining epigenetic alterations with cancer immunotherapy offers a promising approach to improve therapeutic outcomes by targeting the complex biology of tumors. Epigenetic mechanisms such as DNA methylation, histone modifications, and non-coding RNAs (ncRNAs) play a dual role in maintaining immune homeostasis and promoting cancer progression. Changes like hypomethylation in tumor cells can contribute to immune evasion and treatment resistance. Advances in epigenetic tools, particularly clustered regularly interspaced short palindromic repeat (CRISPR) and their associated protein (Cas9)-based

Иммунофенотифицирование крови пациентов с множественным склерозом в диагнозе указывает на классическую подгруппу моноцитов, связанную с эволюцией болезней.

ВВЕДЕНИЕ: Торговля миелоидными клетками с периферии в центральную нервную систему является ключевым фактором в многократном склерозе (МС) посредством представления антигенов, секреции цитокинов и процессов ремонта. МЕТОДЫ: Комбинация массовой цитометрии на кровяных клетках от 60 пациентов, проходящих диагностику, и 29 здоровых методов контроля, а также секвенирование с одной клеткой РНК на спаренных образцах крови и цереброспинной жидкости (CSF), взятых из 5 пациентов с миэлоидными клетками. Результаты: Исследование отсека Myeloid показало обогащение специфической классической популяции моноци

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… Whether this mechanism is involved in monocyte/T-cell enhanced interaction supporting T-cell pathological activity or whether demethylation of this gene impacts related genes expression ( 66 ) contributing to monocyte pathogenicity hence has to be studied. …

Sildenafil, a Type-5 Phosphodiesterase Inhibitor, Fails to Reverse Myeloid-Derived Suppressor Cell-Mediated T Cell Suppression in Cells Isolated From Tuberculosis Patients.

Successful TB treatment is hampered by increasing resistance to the two most effective first-line anti-TB drugs, namely isoniazid and rifampicin, thus innovative therapies focused on host processes, termed host-directed therapies (HDTs), are promising novel approaches for increasing treatment efficacy without inducing drug resistance. We assessed the ability of Sildenafil, a type-5 phosphodiesterase inhibitor, as a repurposed compound, to serve as HDT target, by counteracting the suppressive effects of myeloid-derived suppressor cells (MDSC) obtained from active TB cases on T-cell responsivene

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… Identification of the Cytochrome P450 Enzymes Involved in the N-Demethylation of Sildenafil. Br J Clin Pharmacol (2001) 51:239–48. doi: 10.1046/j.1365-2125.2001.00318.x 64. Cao L, Greenblatt DJ, Kwara A. …

SFRP5 inhibits melanin synthesis of melanocytes in vitiligo by suppressing the Wnt/β-catenin signaling.

Secreted frizzled-related protein 5 (SFRP5) plays a pivotal role in regulating the development of many tissues and organs, however, as an inhibitor of Wnt signaling, the role of SFRP5 in vitiligo remains unknown. Hence, we speculated that SFRP5 might be associated with melanogenesis in melanocytes by regulating Wnt signaling in vitiligo. In this study, we found that SFRP5 was overexpressed in the skin lesions of patients with vitiligo. Compared with that in normal epidermal melanocytes (PIG1), the expression of SFRP5 was increased in vitiligo melanocytes (PIG3V). To investigate the effect of S

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… silencing of SFRP5 promotes the metastasis and invasion of chondrosarcoma, 80 and SFRP5 methylation is closely related to the incidence of colorectal cancer and poor prognosis of gastric cancer. 81 , 82 Therefore, we speculate that in vitiligo skin lesions, SFRP5 expression may increase due to its demethylation …

Phase II trial of single-agent panobinostat consolidation improves responses after sub-optimal transplant outcomes in multiple myeloma.

Panobinostat is a pan-deacetylase inhibitor that modulates the expression of oncogenic and immune-mediating genes involved in tumour cell growth and survival. We evaluated panobinostat-induced post-transplant responses and identified correlative biomarkers in patients with multiple myeloma who had failed to achieve a complete response after autologous transplantation. Patients received panobinostat 45 mg administered three-times weekly (TIW) on alternate weeks of 28-day cycles commencing 8-12 weeks post-transplant. Twelve of 25 patients (48%) improved their depth of response after a median (ra

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… A histone deacetylase inhibitor enhances expression of genes inhibiting Wnt pathway and augments activity of DNA demethylation reagent against nonsmall‐cell lung cancer. Int J Cancer. 2017;140:2375–86. 46. …