A novel model combining genes associated with disulfidptosis and glycolysis to predict breast cancer prognosis, molecular subtypes, and treatment response.

Breast cancer (BC) is a heterogeneous malignancy with a dismal prognosis. Disulfidptosis is a novel type of regulated cell death that happens in the presence of glucose deficiency and is linked to the metabolic process of glycolysis. However, the mechanism of action of disulfidptosis and glycolysis-related genes (DGRG) in BC, as well as their prognostic value in BC patients, remain unknown. After identifying the differentially expressed DGRG in normal and BC tissues, a number of machine learning algorithms were utilized to select essential prognostic genes to develop a model, including SLC7A11, CACNA1H, SDC1, CHST1, and TFF3. The expression characteristics of these genes were then examined using single-cell RNA sequencing, and BC was classified into three clusters using "ConsensusClusterPlus" based on these genes. The DGRG model's median risk score can categorize BC patients into high-risk and low-risk groups. Furthermore, we investigated variations in clinical landscape, immunoinvasion analysis, tumor immune dysfunction and rejection (TIDE), and medication sensitivity in patients in the DGRG model's high- and low-risk groups. Patients in the low-risk group performed better on immunological and chemotherapeutic therapies and had lower TIDE scores. In conclusion, the DGRG model we developed has significant clinical application potential because it can accurately predict the prognosis of BC, TME, and pharmacological treatment responses.

Petroleum ether extract of Schisandra sphenanthera prevents hyperglycemia and insulin resistance in association with modulation of sweet taste receptors and gut microbiota in T2DM rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra sphenanthera (Schisandra sphenanthera Rehd. et Wils.) is the dried mature fruit of Schisandra sphenanthera, a plant in the Magnoliaceae family. It was used in the treatment of diabetes mellitus in the Jade Fluid Decoction and the Xiaoke pills, which were recorded in ancient books. However, its mechanism of action in the treatment of type 2 diabetes mellitus (T2DM) was unclear and needs further study. AIM OF THE STUDY: This research aimed to investigate the chemical composition and lignan content of Schisandra sphenanthera petroleum ether parts (SPEP) and to evaluate the effects of SPEP on sweet taste receptors (STRs) and intestinal flora in rats on a high-fat diet (HFD). Additionally, the relationships between SPEP and hyperglycemia and insulin resistance were examined. MATERIALS AND METHODS: GC-MS was used to determine the chemical composition of SPEP, and HPLC was used to determine the lignin content. A combination of the HFD and the administration of streptozotocin (STZ) was employed to generate a rat model of T2DM. Petroleum ether extracts from Schisandra sphenanthera were used as the focus of the research to evaluate the effects of these extracts on the glucolipid metabolism of T2DM rats, as well as the underlying mechanisms. RESULTS: Analysis of the GC-MS spectrum of SESP revealed a total of 58 compounds. HPLC analysis revealed that SPEP had the highest concentration of Schisandrin A and the lowest concentration of Schisandrol A. The drug administration intervention resulted in a significant decrease in body weight and pancreatic weight of diabetic rats compared to the Normal group. When compared to the Model group, the body weight of rats in the drug administration group and the Metformin group had a more moderate decrease, while the pancreatic weight and pancreatic-to-body ratio increased. The Model group shown significant increases in FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, and NEFA, as well as significant decreases in HDL-C and SOD, when compared to the Normal group (P < 0.05). The administration of each group was found to be significantly effective in decreasing FBG, OGTT, GHb, TC, TG, LDL-C, ALT, AST, MDA, FINS, NEFA, while increasing HDL-C and SOD when compared to the Model group. The application of SPEP had a positive impact on hepatocyte swelling, hepatocyte degeneration, and necrosis, as well as the morphological structure of pancreatic islet cells. Furthermore, the protein expression levels of T1R2, TRPM5 and GLP-1 in the small intestine of the Model group were reduced. After a period of six weeks, the protein expression levels began to align more closely with those of the Normal group of rats. Analysis of 16S rRNA sequencing revealed that the intestinal microbiota of diabetic rats was significantly disrupted, with a decrease in the abundance of the Firmicutes phylum and an increase in the abundance of the Bacteroidetes phylum. Furthermore, the composition of the dominant genus was distinct from that of the control group. After the drug intervention, the microbiota of diabetic rats was significantly altered, exhibiting a higher abundance and diversity, as well as a significant enrichment of the community. The SPEP treatment resulted in a significant increase in acetic acid, propionic acid, and butyric acid. CONCLUSIONS: The findings of this research indicated that SPEP could be effective in treating T2DM through the regulation of STRs, the adjustment of disturbed metabolite levels, and the alteration of intestinal flora.

Optimization of fermentation conditions and medium components for chrysomycin a production by Streptomyces sp. 891-B6.

BACKGROUND: Chrysomycin A (CA) is a promising antibiotic for treatment of Gram-positive bacterial infections and cancers. In order to enhance CA yield, optimization of fermentation conditions and medium components was carried out on strain Streptomyces sp. 891-B6, an UV-induced mutant with improved CA titer compared with its wide-type marine strain 891. RESULTS: Using one-way experiment, the optimal fermentation conditions for CA production in 1-L shake flask were obtained as follows: 12 days of fermentation time, 5 days of seed age, 5% of inoculum volume ratio, 200 mL of loading volume and 6.5 of initial pH. By response surface methodology, the optimal medium components determined as glucose (39.283 g/L), corn starch (20.662 g/L), soybean meal (15.480 g/L) and CaCO3 (2.000 g/L). CONCLUSION: Validation tests showed that the maximum yield of CA reached 1601.9 ± 56.7 mg/L, which was a 60% increase compared to the initial yield (952.3 ± 53.2 mg/L). These results provided an important basis for scale-up production of CA by strain 891-B6.

Thyroid function and polycystic ovary syndrome: a Mendelian randomization study.

Background: Multiple evidence suggests that thyroid function is associated with polycystic ovary syndrome (PCOS), but whether thyroid function is causally related to PCOS is unclear. To investigate whether the association reflect causality, a Mendelian randomization (MR) analysis was conducted. Methods: Single nucleotide polymorphisms (SNPs) involved in this study were acquired from The ThyroidOmics Consortium and the IEU Open Genome-wide association study (GWAS) database, respectively. In forward MR analysis, we included normal free thyroxine (FT4, n=49,269), normal thyroid-stimulating hormone (TSH, n=54,288), hypothyroidism (n=53,423) and hyperthyroidism (n=51,823) as exposure. The outcome was defined as PCOS in a sample size of 16,380,318 individuals. The exposure in the reverse MR analyses was chosen as PCOS, while the outcome consisted of the four phenotypes of thyroid function. The inverse-variance weighted (IVW) method was performed as the major analysis, supplemented by sensitivity analyses. Results: The occurrence of PCOS was associated with increased risk of hyperthyroidism (IVW, OR=1.08, 95%CI=1.02-1.13, P=0.004). No evidence suggested that other phenotypes of thyroid function were related to PCOS. Conclusions: Our findings demonstrate a cause-and-effect connection between PCOS and hyperthyroidism. The study established foundation for further investigation for interaction between thyroid function and PCOS.

Phage Display Screening of Anchor Peptides for Red Blood Cell-Derived Extracellular Vesicles.

Extracellular vesicles (EVs) are increasingly used for disease diagnosis and treatment. Among them, red blood cell-derived EVs (RBC-EVs) have attracted great attention due to their abundant sources and low risks of gene transfer (RBC-EVs lack nuclear and mitochondrial DNA). Here, we first revealed the high expression level of membrane protein solute carrier family 4 member 1 (SLC4A1) in RBC-EVs through proteomic analysis. We then identified several binding peptides with high affinity for the SLC4A1 extracellular domain (SLC4A1-EC) from phage display library screening. A high affinity of SLC4A1-EC and the three peptides (XRB2, XRE4, and XRH7) were assessed in vitro using surface plasmon resonance analysis and SDS-polyacrylamide gel electrophoresis (SDS-PAGE). The binding sites of SLC4A1-EC and polypeptides were further predicted by LigPlot + analysis, and the results showed that these three polypeptides could bind to part of the hydrophobic residues of SLC4A1-EC. The binding efficiency of the anchor peptides to the RBC-EVs was further verified by flow cytometry and fluorescence imaging. In conclusion, we successfully screened three specific RBC-EV-targeting peptides which could potentially be utilized for isolating RBC-derived EVs from serum samples. More importantly, this peptide could be coupled with targeting peptides to modify RBC-EVs for drug delivery. Our work will provide a viable method for optimizing the function of RBC-EVs.

Genus Helleborus: a comprehensive review of phytochemistry, pharmacology and clinical applications.

The genus Helleborus belongs to the Ranunculaceae family, distributed in southeastern Europe and western Asia. In folk medicine, it is commonly used as an anti-inflammatory and analgesic medicine for rheumatoid arthritis and bruises. Through reviewing recent articles, it was found that two hundred and twenty-six compounds have been isolated and identified from the genus Helleborus. These compounds include steroids, flavonoids, phenylpropanoids, lignans, anthraquinones, phenolics and others. Among them, the main chemical constituents are steroids. Pharmacological studies show Helleborus has anti-cancer, immunomodulatory, anti-inflammatory, analgesic, anti-hyperglycaemic, antioxidant and antibacterial properties. This article reviews the botany, phytochemistry, pharmacological effects and clinical applications of the genus Helleborus. Hopefully, it will provide a reference for in-depth research and exploitation of the genus Helleborus.

Marine Streptomyces-Derived Novel Alkaloids Discovered in the Past Decade.

Natural alkaloids originating from actinomycetes and synthetic derivatives have always been among the important suppliers of small-molecule drugs. Among their biological sources, Streptomyces is the highest and most extensively researched genus. Marine-derived Streptomyces strains harbor unconventional metabolic pathways and have been demonstrated to be efficient producers of biologically active alkaloids; more than 60% of these compounds exhibit valuable activity such as antibacterial, antitumor, anti-inflammatory activities. This review comprehensively summarizes novel alkaloids produced by marine Streptomyces discovered in the past decade, focusing on their structural features, biological activity, and pharmacological mechanisms. Future perspectives on the discovery and development of novel alkaloids from marine Streptomyces are also provided.

Adverse Effects of Gefitinib on Skin and Colon in a Lung Cancer Mouse Model.

BACKGROUND: Gefitinib, an Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitor (EGFR-TKI), frequently causes side effects when used to treat non-small cell lung cancer. OBJECTIVE: The purpose of this experiment was to investigate the side effect of gefitinib on the skin and colon of mice. METHODS: Male Balb/c nu-nu nude mice aged 4-5 weeks were used as xenograft tumor models, and gefitinib at 150 mg/kg and 225 mg/kg was started at 9 days after the xenograft tumor grew out. The mice's weights and tumor volumes were tracked concurrently, and the mouse skin adverse reactions and diarrhea were observed during the treatment. The animal tissues were subjected to biochemical and pathological evaluations after 14 days. RESULTS: Gefitinib effectively decreased the size and weight of transplanted tumors in nude mice, while also lowering body weight and raising indexes of the liver and spleen. Gefitinib could cause skin adverse reactions and diarrhea in mice. Further pathological investigation revealed tight junction- related markers in the mice's skin and colon to be reduced and macrophages and neutrophils to be increased after gefitinib treatment. CONCLUSION: The findings imply that gefitinib has negative effects on the skin and colon. Gefitinib- induced skin and colon adverse reactions in mice have been successfully modeled in this study.

A ubiquitin-proteasome system-related signature to predict prognosis, immune infiltration, and therapy efficacy for breast cancer.

The ubiquitin-proteasome system (UPS) is an essential regulatory system for maintaining homeostasis, and its dysfunction may cause various diseases. The activity of proteasome and ubiquitin-conjugating enzymes has been found to be greatly increased in breast cancer (BC), indicating that the heterogeneity of UPS may be related to the progression of BC. Gene data was obtained from The Cancer Genome Atlas and Gene Expression Omnibus databases and performed in multiple algorithms to construct a UPS-related signature for BC. Patients in the UPS low-risk group had greater overall and recurrence-free survival probability than those in the UPS high-risk group. This signature was closely associated with functional enrichment. Some high metabolism-related pathways were more active in the UPS high-risk group. The UPS low-risk group had more abundant anti-tumor immune cells, while in the UPS high-risk group, immunosuppressive cells were dominant. More importantly, we found that the UPS low-risk group was more sensitive to immunotherapy, while the UPS high-risk group responded better to radiotherapy. Drug sensitivity analysis identified more effective chemotherapy drugs in different UPS-related risk groups. This UPS-related signature may serve as a novel biomarker and independent prognostic factor for BC. It can effectively predict prognosis, immune infiltration, and therapy efficacy, providing new strategies for individualized treatment.

Recent Advances in Polypeptide Antibiotics Derived from Marine Microorganisms.

In the post-antibiotic era, the rapid development of antibiotic resistance and the shortage of available antibiotics are triggering a new health-care crisis. The discovery of novel and potent antibiotics to extend the antibiotic pipeline is urgent. Small-molecule antimicrobial peptides have a wide variety of antimicrobial spectra and multiple innovative antimicrobial mechanisms due to their rich structural diversity. Consequently, they have become a new research hotspot and are considered to be promising candidates for next-generation antibiotics. Therefore, we have compiled a collection of small-molecule antimicrobial peptides derived from marine microorganisms from the last fifteen years to show the recent advances in this field. We categorize these compounds into three classes-cyclic oligopeptides, cyclic depsipeptides, and cyclic lipopeptides-according to their structural features, and present their sources, structures, and antimicrobial spectrums, with a discussion of the structure activity relationships and mechanisms of action of some compounds.

Enhanced Cerebral Hemodynamics and Cognitive Function Via Knockout of Dual-Specificity Protein Phosphatase 5.

Alzheimer's Disease (AD) and Alzheimer's Disease-Related Dementias (ADRD) are neurodegenerative disorders. Recent studies suggest that cerebral hypoperfusion is an early symptom of AD/ADRD. Dual-specificity protein phosphatase 5 (DUSP5) has been implicated in several pathological conditions, including pulmonary hypertension and cancer, but its role in AD/ADRD remains unclear. The present study builds on our previous findings, demonstrating that inhibition of ERK and PKC leads to a dose-dependent dilation of the middle cerebral artery and penetrating arteriole, with a more pronounced effect in Dusp5 KO rats. Both ERK and PKC inhibitors resulted in a significant reduction of myogenic tone in vessels from Dusp5 KO rats. Dusp5 KO rats exhibited stronger autoregulation of the surface but not deep cortical cerebral blood flow. Inhibition of ERK and PKC significantly enhanced the contractile capacity of vascular smooth muscle cells from both strains. Finally, a significant improvement in learning and memory was observed in Dusp5 KO rats 24 hours after initial training. Our results suggest that altered vascular reactivity in Dusp5 KO rats may involve distinct mechanisms for different vascular beds, and DUSP5 deletion could be a potential therapeutic target for AD/ADRD. Further investigations are necessary to determine the effects of DUSP5 inhibition on capillary stalling, blood-brain barrier permeability, and neurodegeneration in aging and disease models.

Diagnostic value of contrast-enhanced ultrasound for sentinel lymph node metastasis in breast cancer: an updated meta-analysis.

PURPOSE: The status of sentinel lymph nodes (SLN) is an important factor in determining the stage of breast cancer (BC) and the surgical procedure, and also a biomarker of the BC prognosis. This meta-analysis was performed to investigate the diagnostic value of contrast-enhanced ultrasound (CEUS) for SLN metastasis. METHODS: A systematic search was conducted for relevant articles published in the PubMed, Embase, Web of Science, OVID databases, and Cochrane Library from inception to March 2023. We calculated the sensitivity, specificity, positive and negative likelihood ratio (PLR; NLR), diagnostic odds ratio (DOR), and summary receiver operator characteristic (SROC) curve to evaluate the diagnostic efficacy of CEUS in SLN metastasis. Subgroup analysis was also performed to investigate potential sources of heterogeneity. RESULTS: A total of 12 studies with 1525 patients were included in this meta-analysis. The overall pooled sensitivity and specificity of CEUS in the diagnosis of SLN metastasis were 0.91 (95% CI: 0.84-0.95) and 0.86 (95% CI: 0.78-0.92). The PLR, NLR, and DOR were 6.51 (95% CI: 4.09-10.36), 0.11 (95% CI: 0.07-0.18), and 59.43 (95% CI: 33.27-106.17), respectively, and the area under the SROC curve was determined to be 0.95 (95%CI: 0.92-0.96), all showing excellent diagnostic value. In the subgroup analysis, percutaneous CEUS was more sensitive than intravenous CEUS in the diagnosis of SLN metastases (0.92 versus 0.82, p < 0.05). CONCLUSION: CEUS, especially percutaneous CEUS, is a reliable imaging technique for diagnosing SLN metastasis and providing important information in the stage management of breast cancer.

Enhanced Transdermal Peptide-Modified Flexible Liposomes for Efficient Percutaneous Delivery of Chrysomycin A to Treat Subcutaneous Melanoma and Intradermal MRSA Infection.

Superficial skin diseases, including skin infections and tumors, are common healthcare burdens. In this study, the in vivo activity of chrysomycin A (CA) is explored, and a transdermal liposomal CA formulation is further constructed for the simultaneous treatment of cutaneous melanoma and cutaneous methicillin-resistant Staphylococcus aureus (MRSA) infection. The prepared liposomes (TD-LP-CA) display a strong antitumor effect with an IC50 value of less than 0.1 µm in B16-F10 cells, suppress the proliferation of MRSA with a minimum inhibitory concentration (MIC) of 1 µm, and eradicate established MRSA biofilms at 10× MIC in vitro. More importantly, TD-LP-CA shows enhanced stratum corneum (SC) penetration, reaching more than 500 µm beneath the skin's surface due to modification with the TD peptide, and demonstrates excellent subcutaneous tumor penetration after skin application in vivo. TD-LP-CA displays an excellent therapeutic effect against intradermal MRSA infection in mice after topical dermal administration, as well as a moderate inhibitory effect on subcutaneous melanoma with a 75% tumor inhibition rate. The liposomes prepared herein can be a promising carrier for transcutaneous CA transfer for the treatment of superficial diseases such as skin tumors and infections due to their ability to overcome the skin barrier.

Chrysomycin A Regulates Proliferation and Apoptosis of Neuroglioma Cells via the Akt/GSK-3ß Signaling Pathway In Vivo and In Vitro.

Glioblastoma (GBM) is a major type of primary brain tumor without ideal prognosis and it is therefore necessary to develop a novel compound possessing therapeutic effects. Chrysomycin A (Chr-A) has been reported to inhibit the proliferation, migration and invasion of U251 and U87-MG cells through the Akt/GSK-3ß signaling pathway, but the mechanism of Chr-A against glioblastoma in vivo and whether Chr-A modulates the apoptosis of neuroglioma cells is unclear. The present study aims to elucidate the potential of Chr-A against glioblastoma in vivo and how Chr-A modulates the apoptosis of neuroglioma cells. Briefly, the anti-glioblastoma activity was assessed in human glioma U87 xenografted hairless mice. Chr-A-related targets were identified via RNA-sequencing. Apoptotic ratio and caspase 3/7 activity of U251 and U87-MG cells were assayed via flow cytometry. Apoptosis-related proteins and possible molecular mechanisms were validated via Western blotting. The results showed that Chr-A treatment significantly inhibits glioblastoma progression in xenografted hairless mice, and enrichment analysis suggested that apoptosis, PI3K-Akt and Wnt signaling pathways were involved in the possible mechanisms. Chr-A increased the apoptotic ratio and the activity of caspase 3/7 in U251 and U87-MG cells. Western blotting revealed that Chr-A disturbed the balance between Bax and Bcl-2, activating a caspase cascade reaction and downregulating the expression of p-Akt and p-GSK-3ß, suggesting that Chr-A may contribute to glioblastoma regression modulating in the Akt/GSK-3ß signaling pathway to promote apoptosis of neuroglioma cells in vivo and in vitro. Therefore, Chr-A may hold therapeutic promise for glioblastoma.

Discovery of 2,5-disubstituted furan derivatives featuring a benzamide motif for overcoming P-glycoprotein mediated multidrug resistance in MCF-7/ADR cell.

P-glycoprotein (P-gp) is one of the drug efflux transporters that triggers multidrug resistance (MDR) in cells. Herein, by utilizing the strategies of active skeleton splicing and structural optimization on the lead compound 5 m, a total of 50 novel 2,5-disubstituted furan derivatives were designed, synthesized, and screened for P-gp inhibitory activity. The structure-activity relationship analysis enabled the identification of an important pharmacophore N-phenylbenzamide, which resulted in the discovery of a promising drug lead compound Ⅲ-8. Ⅲ-8 possesses broad-spectrum reversal activity and low toxicity in MCF-7/ADR cells. Western blot and Rh123 accumulation assay demonstrated that Ⅲ-8 displayed the reversal activity by inhibiting P-gp efflux. Molecular docking analysis indicated a potent affinity of Ⅲ-8 to P-gp by forming H-bond interactions with residues Asn 721 and Met 986. Ⅲ-8 was determined to be a highly effective and safe P-gp inhibitor in an MCF-7/ADR xenograft mouse model.

Novel Benzo Five-Membered Heterocycle Derivatives as P-Glycoprotein Inhibitors: Design, Synthesis, Molecular Docking, and Anti-Multidrug Resistance Activity.

A proposed strategy to overcome multidrug resistance (MDR) of anticancer drugs in chemotherapy is to disable the efflux function of P-glycoprotein (P-gp). In this study, based on ring-merging and fragment-growing strategies, 105 novel benzo five-membered heterocycle derivatives were designed, synthesized, and screened. Exploration of the structure-activity relationship (SAR) led to the identification of d7 with low cytotoxicity and promising reversal activity to doxorubicin in MCF-7/ADR cells. Furthermore, the mechanism studies revealed that the reversal activity of d7 stemmed from the inhibition of P-gp efflux. Molecular docking further clarified the observed trends in SAR with d7 displaying potent affinity to P-gp. Additionally, coadministration of d7 with doxorubicin achieved stronger antitumor activity in a xenograft model than doxorubicin alone. These results suggest that d7 is a potential MDR reveal agent acting as a P-gp inhibitor and provides guidelines for the future development of new P-gp inhibitors.

Discovery of New Siderophores from a Marine Streptomycetes sp. via Combined Metabolomics and Analysis of Iron-Chelating Activity.

The marine-derived Streptomyces sp. FIMYZ-003 strain was found to produce novel siderophores with yields negatively correlated with the iron concentration in the medium. Mass spectrometry (MS)-based metabolomics coupled with metallophore assays identified two novel α-hydroxycarboxylate-type siderophores, fradiamines C and D (3 and 4), together with two related known siderophores, fradiamines A and B (1 and 2). Their chemical structures were elucidated by nuclear magnetic resonance (NMR) and MS experiments. The annotation of a putative fra biosynthetic gene cluster enabled us to propose the biosynthetic pathway of fradiamines A-D. Furthermore, the solution-phase iron-binding activity of fradiamines was evaluated using metabolomics, confirming them as general iron scavengers. Fradiamines A-D exhibited Fe(III) binding activity equivalent to that of deferoxamine B mesylate. Growth analysis of pathogenic microbes demonstrated that fradiamine C promoted the growth of Escherichia coli and Staphylococcus aureus, but fradiamines A, B, and D did not. The results indicate that fradiamine C may serve as a novel iron carrier applicable to antibiotic delivery strategies to treat and prevent foodborne pathogens.

Cryo-EM structure of human heptameric pannexin 2 channel.

Pannexin 2 (Panx2) is a large-pore ATP-permeable channel with critical roles in various physiological processes, such as the inflammatory response, energy production and apoptosis. Its dysfunction is related to numerous pathological conditions including ischemic brain injury, glioma and glioblastoma multiforme. However, the working mechanism of Panx2 remains unclear. Here, we present the cryo-electron microscopy structure of human Panx2 at a resolution of 3.4 Å. Panx2 structure assembles as a heptamer, forming an exceptionally wide channel pore across the transmembrane and intracellular domains, which is compatible with ATP permeation. Comparing Panx2 with Panx1 structures in different states reveals that the Panx2 structure corresponds to an open channel state. A ring of seven arginine residues located at the extracellular entrance forms the narrowest site of the channel, which serves as the critical molecular filter controlling the permeation of substrate molecules. This is further verified by molecular dynamics simulations and ATP release assays. Our studies reveal the architecture of the Panx2 channel and provide insights into the molecular mechanism of its channel gating.

Marine Organisms as a Prolific Source of Bioactive Depsipeptides.

Depsipeptides, an important group of polypeptides containing residues of hydroxy acids and amino acids linked together by amide and ester bonds, have potential applications in agriculture and medicine. A growing body of evidence demonstrates that marine organisms are prolific sources of depsipeptides, such as marine cyanobacteria, sponges, mollusks, microorganisms and algae. However, these substances have not yet been comprehensively summarized. In order to enrich our knowledge about marine depsipeptides, their biological sources and structural features, as well as bioactivities, are highlighted in this review after an extensive literature search and data analysis.