Multi-target antibacterial mechanism of ruthenium polypyridine complexes with anthraquinone groups against Staphylococcus aureus.

Three new Ru(ii) complexes, [Ru(dtb)2PPAD](PF6)2 (Ru-1), [Ru(dmob)2PPAD](PF6)2 (Ru-2) and [Ru(bpy)2PPAD](PF6)2 (Ru-3) (dtb = 4,4'-di-tert-butyl-2,2'-bipyridine, dmob = 4,4'-dimethyl-2,2'-bipyridine, bpy = 2,2'-bipyridine and PPAD = 2-(pyridine-3-yl)-1H-imidazo[4,5f][1.10]phenanthracene-9,10-dione), were synthesized and characterized by 1H NMR and 13C NMR spectroscopy, HRMS and HPLC. Among them, Ru-1 showed excellent antimicrobial activity against Gram-positive bacteria Staphylococcus aureus (minimum inhibitory concentration (MIC) = 1 µg mL-1) and low hemolytic and cytotoxic activity. In addition, Ru-1 showed obviously rapid bactericidal activity, low resistance rate, bacterial biofilm destroying activity and high biosafety in vivo. Moreover, skin infection models and a mouse model of sepsis indicated that the anti-infective efficacy of Ru-1 was comparable to that of vancomycin. Mechanism exploration results showed that the antibacterial behavior is probably related with targeting of the bacterial cell membrane and inhibiting topoisomerase I.

Past and present: a bibliometric study on polycystic ovary syndrome.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common gynecological endocrine disease that has a great impact on women's physical and mental health. It is a burden to social and patients' economy. In recent years, researchers' understanding of PCOS has reached a new level. However, many PCOS reports have different directions, and overlapping phenomena exist. Therefore, clarifying the research status of PCOS is important. This study aims to summarise the research status of PCOS and predict the hot spots of PCOS in the future by Bibliometricx. RESULTS: The keywords of PCOS research focused on PCOS, insulin resistance (IR), obesity and metformin. Keywords plus co-occurrence network showed that PCOS, IR and prevalence were hot spots in the recent 10 years. Moreover, we found that gut microbiota may be a carrier that can be used to study hormone levels, IR-related mechanisms, prevention and treatment in the future. CONCLUSIONS: This study is helpful for researchers to quickly grasp the current situation of PCOS research and enlighten researchers to explore new problems in PCOS.

Ferroptosis-Related Long Noncoding RNAs as Prognostic Biomarkers for Ovarian Cancer.

Ovarian cancer (OC) is a highly malignant gynecologic tumor with few treatments available and poor prognosis with the currently available diagnostic markers and interventions. More effective methods for diagnosis and treatment are urgently needed. Although the current evidence implicates ferroptosis in the development and therapeutic responses of various types of tumors, it is unclear to what extent ferroptosis affects OC. To explore the potential of ferroptosis-related genes as biomarkers and molecular targets for OC diagnosis and intervention, this study collected several datasets from The Cancer Genome Atlas-OC (TCGA-OC), analyzed and identified the coexpression profiles of 60 ferroptosis-related genes and two subtypes of OC with respect to ferroptosis and further examined and analyzed the differentially expressed genes between the two subtypes. The results indicated that the expression levels of ferroptosis genes were significantly correlated with prognosis in patients with OC. Single-factor Cox and LASSO analysis identified eight lncRNAs from the screened ferroptosis-related genes, including lncRNAs RP11-443B7.3, RP5-1028K7.2, TRAM2-AS1, AC073283.4, RP11-486G15.2, RP11-95H3.1, RP11-958F21.1, and AC006129.1. A risk scoring model was constructed from the ferroptosis-related lncRNAs and showed good performance in the evaluation of OC patient prognosis. The high- and low-risk groups based on tumor scores presented obvious differences in clinical characteristics, tumor mutation burden, and tumor immune cell infiltration, indicating that the risk score has a good ability to predict the benefit of immunotherapy and may provide data to support the implementation of precise immunotherapy for OC. Although in vivo tests and research are needed in the future, our bioinformatics analysis powerfully supported the effectiveness of the risk signature of ferroptosis-related lncRNAs for prognosis prediction in OC. The findings suggest that these eight identified lncRNAs have great potential for development as diagnostic markers and intervention targets for OC and that patients with high ferroptosis-related lncRNA expression will receive greater benefits from conventional chemotherapy or treatment with ferroptosis inducers.

Therapeutic Prospects of Polysaccharides for Ovarian Cancer.

Ovarian cancer (OC) is ranked as the leading cause of death among cancers of the female reproductive tract. First-line platinum treatment faces the severe challenges associated with the patient relapse and poor prognosis. Thus, it is imperative to develop natural antitumor drugs for OC with high efficacy. Natural polysaccharides have significant biological activities and antitumor effects. Our work has demonstrated that polysaccharides play key roles by inhibiting the cell proliferation and growth, regulating the tumor cell cycle, inducing apoptosis, suppressing the tumor cell migration and invasion, improving the immunomodulatory activities, and enhancing the efficacy of chemotherapy (cisplatin) in OC, which provide powerful evidence for the application of polysaccharides as novel anticancer agents, supplementary remedies, and adjunct therapeutic agents alone or in combination with cisplatin for preventing and treating the OC.

Synthesis and In Vitro anti-HCV and Antitumor Evaluation of Schisandronic Acid Derivatives.

BACKGROUND: Schisandronic acid (SA), a triterpenoid from fruits of Schisandra sphenanthera, inhibited pan-genotypic HCV entry into human hepatocytes by interfering with virion-cell membrane fusion. It was a promising lead compound for the development of novel HCV entry inhibition agents. OBJECTIVE: The aim of the present study is to search for compounds with more potent anti-HCV and antitumor activities and explore SARs. A series of novel derivatives of SA were designed and synthesized and evaluated for in vitro, their anti-HCV and antitumor activities. METHODS: SA derivatives were synthesized by reduction, condensation, esterification or amidation. The anti-HCV activity of title compounds was tested by inhibition on HCVcc infection of Huh7 cells, and a preliminary MOA study was conducted by determining inhibition on HCVpp entry into Huh7 cells. The antitumor activity in vitro was determined by MTT methods. RESULTS: In total, 24 novel derivatives were synthesized. Most of the compounds inhibited HCVcc infection. Compounds 5h and 6 showed the most potent anti-HCVcc activities and inhibition of HCVpp entry into Huh7 cells without obvious cytotoxicity. Most of the title compounds showed potent in vitro antitumor activities against Bel7404 and SMMC7721 tumor cell lines. Compounds 5j and 6 exhibited more potent antitumor activity than positive control SA and DOX. CONCLUSION: Structural modification of SA could lead to the discovery of potent anti-HCV or antitumor agents. Compounds 5h, 5j and 6 were promising lead compounds for development of novel HCV entry inhibition or antitumor agents.