Cervical cancer (CC) is the second most common female cancer. Excellent clinical outcomes have been achieved with current screening tests and medical treatments in the early stages, while the advanced stage has a poor prognosis. Nicotinamide adenine dinucleotide (NAD+) metabolism is implicated in cancer development and has been enhanced as a new therapeutic concept for cancer treatment. This study set out to identify an NAD+ metabolic-related gene signature for the prospect of cervical cancer survival and prognosis. Tissue profiles and clinical characteristics of 293 cervical cancer patients and normal tissues were downloaded from The Cancer Genome Atlas database to obtain NAD+ metabolic-related genes. Based on the differentially expressed NAD+ metabolic-related genes, cervical cancer patients were divided into two subgroups (Clusters 1 and 2) using consensus clustering. In total, 1404 differential genes were acquired from the clinical data of these two subgroups. From the NAD+ metabolic-related genes, 21 candidate NAD+ metabolic-related genes (ADAMTS10, ANGPTL5, APCDD1L, CCDC85A, CGREF1, CHRDL2, CRP, DENND5B, EFS, FGF8, P4HA3, PCDH20, PCDHAC2, RASGRF2, S100P, SLC19A3, SLC6A14, TESC, TFPI, TNMD, ZNF229) were considered independent indicators of cervical cancer prognosis through univariate and multivariate Cox regression analyses. The 21-gene signature was significantly different between the low- and high-risk groups in the training and validation datasets. Our work revealed the promising clinical prediction value of NAD+ metabolic-related genes in cervical cancer.

High‐risk human papillomavirus (HR‐HPV) is the main etiological factor for cervical cancer. Accumulating evidence has suggested the active role of metabolites in the initiation and progression of cancers. This study explored the plasma metabolic profiles of HPV‐16 positive (HPV16 (+)), HPV‐18 positive (HPV18 (+)), and HPV negative (CTL) individuals using a nontargeted metabolomics approach. C8 ceramide‐1‐Phosphate (d18 : 1/8 : 0) was found to inhibit cervical cancer cell proliferation and migration in vitro, evidenced by CCK8 experiments, a cell migration test, RT‐qPCR, and western blotting. The underlying mechanism demonstrated that C8 inhibited proliferation and migration in cervical cancer cells via the MAPK/JNK1 signaling pathway. These findings may contribute to the clinical treatment of HR‐HPV‐induced cervical cancer by intervening in its initiation and progression.

Introduction: Polycystic ovary syndrome (PCOS) is a complex endocrine disorder that often coexists with a metabolic disorder. Studies have demonstrated that the malfunction of adipose tissue, particularly abdominal adipose tissue, could exacerbate reproductive and metabolic problems in PCOS patients. Adipose tissue-secreted signaling mediators (e.g., lipids and metabolites) would then interact with other body organs, including the ovary, to maintain the systemic equilibrium.Methods: In this study, we examined adipose samples from PCOS patients and unaffected individuals using a liquid chromatography–mass spectrometry-based metabonomics approach (LC–MS/MS). PCOS biomarkers were selected using multivariate statistical analysis.Results: Our pathway analysis revealed that these differential metabolites could be engaged in inflammatory diseases and mitochondrial beta-oxidation. We further developed an in vitro PCOS cell model to examine the effects of hyperandrogenism on granulosa cells and related metabolic disorders. We noted that isoleucine recovered the promotive effect on cell apoptosis, inhibitory effect on cell proliferation, sex hormone secretion, and mitochondrial function induced by dehydroepiandrosterone. Our gas chromatography–mass spectrometry targeted analysis (GC–MS/MS) revealed that isoleucine was significantly decreased in PCOS patients.Discussion: Based on these results, we speculate that metabolome alterations are vital in ameliorating PCOS symptoms. This may be a novel therapeutic target for PCOS treatment. Our study provides preliminary evidence that these findings will enhance our ability to accurately diagnose and intervene in PCOS.

Background: Preterm birth (PTB) is the primary cause of infant morbidity and mortality. Moreover, previous studies have established that PTB is related to premature cervical ripening. However, the underlying mechanism remains to be elucidated. This study sought to identify differentially expressed metabolites and investigate their potential biological functions in PTB. Methods: Pregnant C57BL/6 J mice were treated with either LPS or normal saline and cervical alterations before labor were detected by staining. Metabolic profiles in the plasma of PTB and control mice were examined through non-targeted metabonomics analyses, quantitative polymerase chain reaction and immunofluorescence staining were performed on human cervical smooth cells. Results: The study demonstrated that the mRNA and protein levels of α-SMA, SM-22, and calponin in cervical smooth muscle cells of PTB mice were lower while OR was higher at both mRNA and protein levels compared to the CTL group. A total of 181 differentially expressed metabolites were analyzed, among them, 96 were upregulated, while 85 were downregulated in the PTB group. Differentially expressed metabolites may play a role in STAT3, RhoA, mTOR, TGF-β, and NK-κB signaling pathways. Furthermore, when treated with taurine, the levels of α-SMA and SM-22 in human cervical smooth muscle cells were elevated, whereas that of connexin-43 was decreased. Conclusion: Our study highlighted the changes of metabolites in the peripheral blood changed prior to PTB and revealed that these differentially expressed metabolites might participate in the development of premature cervical ripening. Taurine was identified as an important metabolite may modulate human cervical smooth muscle cells. Our study provided new insights into the mechanism underlying premature cervical ripening in PTB.