Laeviganoids A-T, ent-Clerodane-Type Diterpenoids from Croton laevigatus.

Laeviganoids A-T (1-20), 20 new ent-clerodane-type diterpenoids featuring a 2-furanone (1-3) or a furan (4-20) ring, as well as six analogues (21-26), were isolated from the roots of Croton laevigatus. Their structures were determined by spectroscopic data analysis, experimental electronic circular dichroism measurements, and X-ray crystallographic studies. Compounds 4-6, 16, 21-24, and 26 could influence the anti-inflammatory protumoral phenotype of macrophages. Among these compounds, 21 and 26 are the most potent, as evidenced by consistently downregulating the classic anti-inflammatory cytokine IL-10 and upregulating the classic pro-inflammatory cytokine TNF-α on the secretion level in RAW 264.7 cells.

Changed ventral striatum structural covariance and grey matter volume in depression during a one-year follow-up.

Empirical findings suggest reduced cortico-striatal structural connectivity in patients with major depressive disorder (MDD). However, the relationship between the abnormal structural covariance and one-year outcome of first-episode drug-naive patients has not been evaluated. This longitudinal study aimed to identify specific changes of ventral striatum-related brain structural covariance and grey matter volume in forty-two first-episode patients with major depression disorder compared with thirty-seven healthy controls at the baseline and the one-year follow-up conditions. At the baseline, patients showed decreased structural covariance between the left ventral striatum and the bilateral superior frontal gyrus (SFG), bilateral middle frontal gyrus (MFG), right supplementary motor area (SMA) and left precentral gyrus and increased grey matter volume at the left fusiform and left parahippocampus. At the one-year follow-up, patients showed decreased structural covariance between the left ventral striatum and the right SFG, right MFG, left precentral gyrus and left postcentral gyrus, and increased structural covariance between the right ventral striatum and the right amygdala, right hippocampus, right parahippocampus, right superior temporal pole, right insula and right olfactory bulb and decreased volume at the left SMA compared with controls. These findings suggest that specific ventral striatum connectivity changes contribute to the early brain development of the MDD.

Targeting colorectal cancer with Herba Patriniae and Coix seed: Network pharmacology, molecular docking, and in vitro validation.

BACKGROUND: Herba Patriniae and Coix seed (HC) constitute a widely utilized drug combination in the clinical management of colorectal cancer (CRC) that is known for its diuretic, anti-inflammatory, and swelling-reducing properties. Although its efficacy has been demonstrated in a clinical setting, the active compounds and their mechanisms of action in CRC treatment remain to be fully elucidated. AIM: To identify the active, CRC-targeting components of HC and to elucidate the mechanisms of action involved. METHODS: Active HC components were identified and screened using databases. Targets for each component were predicted. CRC-related targets were obtained from human gene databases. Interaction targets between HC and CRC were identified. A "drug-ingredient-target" network was created to identify the core components and targets involved. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analyses were conducted to elucidate the key pathways involved. Molecular docking between core targets and key components was executed. In vitro experiments validated core monomers. RESULTS: Nineteen active components of HC were identified, with acacetin as the primary active compound. The predictive analysis identified 454 targets of the active compounds in HC. Intersection mapping with 2685 CRC-related targets yielded 171 intervention targets, including 30 core targets. GO and KEGG analyses indicated that HC may influence the phosphoinositide 3-kinase (PI3K)/Akt signaling pathway. Molecular docking showed that acacetin exhibited an optimal interaction with AKT1, identifying PI3K, AKT, and P53 as key genes likely targeted by HC during CRC treatment. Acacetin inhibited HT-29 cell proliferation and migration, as well as promoted apoptosis, in vitro. Western blotting analysis revealed increased p53 and cleaved caspase-3 expression and decreased levels of p-PI3K, p-Akt, and survivin, which likely contributed to CRC apoptosis. CONCLUSION: Acacetin, the principal active compound in the HC pair, inhibited the proliferation and migration of HT-29 cells and promoted apoptosis through the PI3K/Akt/p53 signaling pathway.

Antimicrobial abietane-type diterpenoids from Torreya grandis.

Twelve undescribed abietane-type diterpenoids, along with ten known analogues were isolated from the twigs and leaves of Torreya grandis var. merrillii Hu. Their structures were characterized by spectroscopic data analyses, single-crystal X-ray diffraction, and ECD spectra. Torgranols A-C possess three different architectures shaped via a common 6,7-seco-procedure and subsequent ring formations. In particular, torgranol A represents the first example of a 6,7-seco-abietane diterpenoid featuring a unique oxygen bridge between C-3 and C-6. The biosynthetic pathways for torgranols A-C were proposed. Some compounds displayed antimicrobial activities against Mycobacterium tuberculosis and/or Staphylococcus aureus.

Transformation from polycythemia vera to acute promyelocytic leukemia: Case report and literature review.

INTRODUCTION: Transformation from chronic myeloproliferative neoplasm to acute leukemia is a feature of myeloproliferative neoplasm; however, the rate is not high. Transformation to acute promyelocytic leukemia is rare. Here, we report a case of transformation of polycythemia vera to acute promyelocytic leukemia and describe a process of clonal evolution that has not yet been reported. PATIENT CONCERNS: In this case, a 51-year-old woman was diagnosed with polycythemia vera and concomitant JAK2/V617F mutations in July 2019. She underwent intermittent phlebotomy and oral hydroxyurea irregularly. After 2 years, the patient complained of fatigue and poor sleep quality for 2 months. DIAGNOSIS: Further examination revealed marked hypercellularity and grade 1 bone marrow fibrosis with the PML/RARαV variant (23.85% mutation load), WT1-Exon1 (37.8%), WT1-Exon9 (4.1%), JAK3-Exon7 (49.3%), and RELN-Exon55 (45.8%). According to the World Health Organization classification of tumors of hematopoietic and lymphoid tissues, the patient was ultimately diagnosed with a rare transformation of polycythemia vera to acute promyelocytic leukemia. INTERVENTIONS: The patient underwent dual induction therapy with all-trans-retinoic acid and arsenic trioxide. OUTCOMES: After 28 days of induction therapy, the patient achieved complete remission, was compliant and the treatment was well tolerated. CONCLUSION: Polycythemia vera can transform into acute promyelocytic leukemia; therefore, it is important to review bone aspiration and other tests to perform a comprehensive assessment and monitor the disease status, to detect disease progression and intervene early when it transforms into acute promyelocytic leukemia.