Pyrrololactam alkaloids with IL-6 inhibitory activities from the sponge Phakellia fusca collected in the South China Sea.

Sixteen undescribed pyrrololactam alkaloids, including five 2-bromopyrrole-ε-lactam (1a, 1b, 4a, 4b and 5), two 3-bromopyrrole-ε-lactam (9 and 10), eight pyrrole-ε-lactam (2a-3 and 6a-8), and one pyrrole-δ-lactam alkaloids (11), along with three previously reported compounds (12-14) were isolated from the marine sponge Phakellia fusca collected in the South China Sea. The planar structures were determined by NMR and MS analyses, while the absolute configurations were clearly elucidated by comparing the experimental and calculated ECD spectra. Compounds 2a, 2b, 4a-7b, 10, 12 and 13 exhibited anti-inflammatory activity in inhibiting the production of inflammatory cytokines IL-6 in LPS-induced RAW264.

Marine derived macrolide bryostatin 4 inhibits the TGF-β signaling pathway against acute erythroleukemia.

Purpose: Acute erythroleukemia (AEL) is a rare and highly aggressive subtype of acute myeloid leukemia (AML) with an extremely poor prognosis when treated with available drugs. Therefore, new investigational agents capable of inducing remission are urgently required.

Methods: Bioinformatics analysis, western blot and qRT-PCR were used to reveal the potential biological mechanism of bryostatin 4 (B4), an antineoplastic macrolide derived from the marine bryozoan Bugula neritina.

Marine sponge-derived alkaloid inhibits the PI3K/AKT/mTOR signaling pathway against diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a genetically heterogeneous non-Hodgkin lymphoma that is extremely aggressive and has an intermediate to high malignancy. Some patients still experience treatment failure, relapse, or resistance to rituximab, cyclophosphamide, adriamycin, vincristine, and prednisone (R-CHOP) therapy. Therefore, there is an urgent need for further research on new agents for the treatment of DLBCL.

Sponge-derived alkaloid AP-7 as a sensitizer to cisplatin in the treatment of multidrug-resistant NSCLC via Chk1-dependent mechanisms.

Multidrug resistance is a substantial obstacle in treating non-small cell lung cancer (NSCLC) with therapies like cisplatin (DDP)-based adjuvant chemotherapy and EGFR-tyrosine kinase inhibitors (TKIs). Aaptamine-7 (AP-7), a benzonaphthyridine alkaloid extracted from sponge, has been shown to exhibit a broad spectrum of anti-tumor activity. However, the anti-cancer activity of AP-7 in combination with DDP and its molecular mechanisms in multidrug-resistant NSCLC are not yet clear.

Enhancing thromboprophylaxis after colorectal cancer surgery in China: Bridging the gap between evidence and implementation through pathway optimization.

Background: The CRC-VTE trial conducted in China revealed a significant occurrence of venous thromboembolism (VTE) in patients following colorectal cancer (CRC) surgery, raising concerns about implementing thromboprophylaxis measures. The present study aimed to identify and analyze inappropriate aspects of current thromboprophylaxis practices.

Methods: This study performed an analysis of the CRC-VTE trial, a prospective multicenter study that enrolled 1836 patients who underwent CRC surgery.

A new simplified risk assessment model enhances postoperative prophylaxis of venous thromboembolism in Chinese adult patients with inguinal hernia (CHAT-3): a prospective, multicenter, randomized controlled trial.

Background: Venous thromboembolism (VTE) significantly affects the prognosis of surgical patients with inguinal hernia. The complex Caprini score, commonly used for postoperative VTE risk assessment, poses practical challenges for surgeons in clinical settings.

Methods: The CHAT-3 trial, a prospective, multicenter, randomized controlled trial, compared a simple three-factor model to assess VTE risk against routine practices in postinguinal hernia surgery (IHS) patients.

Marcytoglobosins A and B, Cytochalasans From a Marine Sponge Associated Chaetomium globosum 162105 Fungus.

Two new cytochalasans, marcytoglobosins A (1) and B (2) were isolated from the marine sponge associated fungus Chaetomium globosum 162105, along with six known compounds (3-8). The complete structures of two new compounds were determined based on 1D/2D NMR and HR-MS spectroscopic analyses coupled with ECD calculations. All eight isolates were evaluated for their antibacterial activity.

Mutagenetic analysis of the biosynthetic pathway of tetramate bripiodionen bearing 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione skeleton.

Background: Natural tetramates are a family of hybrid polyketides bearing tetramic acid (pyrrolidine-2,4-dione) moiety exhibiting a broad range of bioactivities. Biosynthesis of tetramates in microorganisms is normally directed by hybrid polyketide synthase (PKS) and nonribosomal peptide synthetase (NRPS) machineries, which form the tetramic acid ring by recruiting trans- or cis-acting thioesterase-like Dieckmann cyclase in bacteria. There are a group of tetramates with unique skeleton of 3-(2H-pyran-2-ylidene)pyrrolidine-2,4-dione, which remain to be investigated for their biosynthetic logics.

Marine sponge-derived alkaloid ameliorates DSS-induced IBD via inhibiting IL-6 expression through modulating JAK2-STAT3-SOCS3 pathway.

Cyanogramide (AC14), a novel alkaloid, isolated from the fermentation broth of the marine-derived Actinoalloteichus cyanogriseus. However, the exact role of AC14 in inflammatory bowel disease (IBD) is poorly understood. Our results demonstrated that AC14 exhibited significant inhibition of IL-6 release in THP-1 cells and a "Caco-2/THP-1" coculture system after stimulation with LPS for 24 h.

Arenarialins A-F, Anti-inflammatory Meroterpenoids with Rearranged Skeletons from the Marine Sponge .

Six new sesquiterpene quinone/hydroquinone meroterpenoids, arenarialins A-F (-), were isolated from the marine sponge collected from the South China Sea. Their chemical structures and absolute configurations were determined by HRMS and NMR data analyses coupled with DP4+ and ECD calculations. Arenarialin A () features an unprecedented tetracyclic 6/6/5/6 carbon skeleton, whereas arenarialins B-D (-) possess two rare secomeroterpene scaffolds.

Discovering the secondary metabolic potential of Saccharothrix.

Rare actinomycetes are highly valued as potential sources of novel bioactive secondary metabolites. Among these rare actinomycetes, the genus Saccharothrix is particularly noteworthy due to its ability to produce a diverse range of bioactive secondary metabolites. With the continuous sequencing of bacterial genomes and the rapid development of bioinformatics technologies, our knowledge of the secondary metabolic potential of Saccharothrix can become more comprehensive, but this space has not been reviewed or explored.

Global Research Hotspots in Venous Thromboembolism Anticoagulation: A Knowledge-Map Analysis from 2012 to 2021.

Background: Venous thromboembolism (VTE) is a common cardiovascular disease that seriously threatens human lives. Anticoagulant therapy is considered to be the cornerstone of VTE treatment. An increasing number of studies has been updated in the VTE anticoagulation field.

Phyllofenones F-M, Scalarane Sesterterpenes from the Marine Sponge .

Eight new scalarane sesterterpenes, phyllofenones F-M (-), together with two known analogues, carteriofenones B and A (-), were isolated from the marine sponge collected from the South China Sea. The structures of these compounds were determined based on extensive spectroscopic and quantum chemical calculation analysis. The antibacterial and cytotoxic activity of these compounds was evaluated.

A novel machine learning model to predict high on-treatment platelet reactivity on clopidogrel in Asian patients after percutaneous coronary intervention.

Background: Various genetic and nongenetic variables influence the high on-treatment platelet reactivity (HTPR) in patients taking clopidogrel.

Aim: This study aimed to develop a novel machine learning (ML) model to predict HTPR in Chinese patients after percutaneous coronary intervention (PCI).

Method: This cohort study collected information on 507 patients taking clopidogrel.

A novel shared decision-making (SDM) tool for anticoagulation management in atrial fibrillation: protocol for a prospective, cluster randomized controlled trial.

Background: Atrial fibrillation (AF) is a common arrhythmia that requires anticoagulation therapy to prevent stroke. However, there is still a significant under-/over-treatment in stroke prevention for patients with AF. The adherence and the risk of bleeding associated with oral anticoagulation therapy (OACs) are major concerns.

Clinical comprehensive evaluation of direct oral anticoagulants for patients with atrial fibrillation in China.

Background: Direct oral anticoagulants (DOACs) are increasingly recommended over warfarin in stroke prevention for patients with non-valvular atrial fibrillation (AF). However, there is an important evidence gap in choosing the most appropriate DOAC for Chinese patients in clinical practice.

Methods: A multi-criteria decision analysis (MCDA) was adopted to build a scoring framework.

The Importance of Clinical Pharmacists in Improving Blood Glucose and Lipid Levels in Patients with Diabetes and Myocardial Infarction.

Purpose: The aim of this study was to evaluate whether intervention by clinical pharmacists can improve blood glucose and lipid levels in diabetic patients with complex medical conditions.

Methods: The retrospective database included 138 patients with diabetes who had presented with acute myocardial infarction (AMI) between January 2019 and October 2021. Blood glucose and lipid levels were measured within 12 weeks and 78 weeks of follow-up.

Dysambiol, an Anti-inflammatory Secomeroterpenoid from a sp. Marine Sponge.

An unusual secomeroterpenoid, dysambiol (), was isolated from a sp. marine sponge collected from the South China Sea. Dysambiol features an unprecedented secomeroterpene scaffold with a rare lactone bridge.

Phakellisins A-E, cyclopeptides from a marine sponge Phakellia sp. guided by LC-MS.

A chemical investigation of the marine sponge Phakellia sp. from the South China Sea yielded five new cyclopeptides, phakellisins A-E (1-5). Structures of these compounds were determined by comprehensive analysis of 1D/2D NMR, HRESIMS/MS spectroscopic data and the advanced Marfey's method.

Secondary metabolites from the marine-derived fungus Y20-2, and their pro-angiogenic activity.

A systematic chemical study of the secondary metabolites of the marine fungus, (No. Y20-2), led to the isolation of 21 compounds, one of which is new (compound ). The structures of the 21 compounds were determined by conducting extensive analysis of the spectroscopic data.

Phyllospongianes A-E, Dinorscalarane Sesterterpenes from the Marine Sponge .

Phyllospongianes A-E (-), five new scalarane derivatives featuring an unprecedented 6/6/6/5 tetracyclic dinorscalarane scaffold, along with the known probable biogenetic precursor, 12-deacetylscalaradial (), were isolated from the marine sponge . The structures of the isolated compounds were determined by analysis of spectroscopic data and electronic circular dichroism experiments. Compounds - are the first 6/6/6/5 tetracyclic scalarane derivatives to be reported within the scalarane family.

Biosynthesis of trialkyl-substituted aromatic polyketide NFAT-133 involves unusual P450 monooxygenase-mediating aromatization and a putative metallo-beta-lactamase fold hydrolase.

The bacterial trialkyl-substituted aromatic polyketides are structurally featured with the unusual aromatic core in the middle of polyketide chain such as TM-123 (), veramycin A (), NFAT-133 () and benwamycin I (), which were discovered from species and demonstrated with antidiabetic and immunosuppressant activities. Though the biosynthetic pathway of - was reported as a type I polyketide synthase (PKS), the PKS assembly line was interpreted inconsistently, and it remains a mystery how the compound was generated. Herein, the PKS assembly logic of - was revised by site-mutagenetic analysis of the PKS dehydratase domains.

LC-MS-Guided Isolation of Cyanogripeptides A-C, Cyclolipopeptides with β-Methyl-Leucine Residues, from an LHW52806.

Cyanogripeptides A-C (-), three new cyclolipopeptides with unusual β-methyl-leucine residues, were identified from an LHW52806 using an LC-MS-guided strategy. The structures of compounds - were elucidated by 1D/2D NMR, HR-MS/MS, and the advanced Marfey's method. The absolute configuration of the β-methyl-leucine residue was determined by a combination of stereoselective biosynthesis of (2,3)-β-methyl-leucine, racemization to its epimer (2,3)-β-methyl-leucine, and the advanced Marfey's method.