Introduction: Periodontitis is an inflammatory disease and its molecular mechanisms is not clear. A recently discovered cell death pathway called cuproptosis, may related to the disease.Methods: The datasets GSE10334 of human periodontitis and control were retrieved from the Gene Expression Omnibus database (GEO) for analysis.Following the use of two machine learning algorithms, least absolute shrinkage and selection operator (LASSO) and support vector machine-recursive feature removal (SVM-RFE) were used to find CRG-based signature. Then the Receiver operating characteristic (ROC) curves was used to evaluate the gene signature's discriminatory ability. The CIBERSORT deconvolution algorithm was used to study the link between hub genes and distinct types of immune cells. Next, the association of the CRGs with immune cells in periodontitis and relevant clusters of cuproptosis were found. The link between various clusters was ascertained by the GSVA and CIBERSORT deconvolution algorithm. Finally, An external dataset (GSE16134) was used to confirm the diagnosis capacity of the identified biomarkers. In addition, clinical samples were examined using qRT-PCR and immunohistochemistry to verifiy the expression of genes related to cuprotosis in periodontitis and the signature may better predict the periodontitis. Results: 15 periodontitis-related DE-CRGs were found,then 11-CRG-based signature was found by using of LASSO and SVM-RFE. ROC curves also supported the value of signature. CIBERSORT results of immune cell signature in periodontitis showed that signature genes is a crucial component of the immune response.The relevant clusters of cuproptosis found that the NFE2L2, SLC31A1, FDX1,LIAS, DLD, DLAT, and DBT showed a highest expression levels in Cluster2 ,while the NLRP3, MTF1, and DLST displayed the lowest level in Cluster 2 but the highest level in Cluster1. The GSVA results also showed that the 11 cuproptosis diagnostic gene may regulate the periodontitis by affecting immune cells. The external dataset (GSE16134) confirm the diagnosis capacity of the identified biomarkers, and clinical samples examined by qRT-PCR and immunohistochemistry also verified that these cuprotosis related signiture genes in periodontitis may better predict the periodontitis. Conclusion: These findings have important implications for the cuproptosis and periodontitis, and highlight further research is needed to better understand the mechanisms underlying this relationship between the cuproptosis and periodontitis.

It has been widely acknowledged that anti-Müllerian hormone (AMH) is a golden marker of ovarian reserve. Declined ovarian reserve (DOR), based on experience from reproductive-aged women, refers to both the quantitative and qualitative reduction in oocytes. This view is challenged by a recent study clearly showing that the quality of oocytes is similar in young women undergoing IVF cycles irrespective of the level of AMH. However, it remains elusive whether AMH indicates oocyte quality in women with advanced age (WAA). The aim of this study was to investigate this issue. In the present study, we retrospectively analysed the data generated from a total of 492 IVF/ICSI cycles (from January 2017 to July 2020), and these IVF/ICSI cycles contributed 292 embryo transfer (ET) cycles (from June 2017 to September 2019, data of day 3 ET were included for analysis) in our reproductive centre. Based on the level of AMH, all patients (= > 37 years old) were divided into 2 groups: the AMH high (H) group and the AMH low (L) group. The parameters of in vitro embryo development and clinical outcomes were compared between the two groups. The results showed that women in the L group experienced severe DOR, as demonstrated by a higher rate of primary diagnosis of DOR, lower antral follicle count (AFC), higher level of basal follicle stimulating hormone (FSH) and cancelation cycles, lower level of E2 production on the day of surge, and fewer oocytes and MII oocytes retrieved. Compared with women in the H group, women in the L group showed slightly reduced top embryo formation rate but a similar normal fertilization rate and blastocyst formation rate. More importantly, we found that the rates of implantation, spontaneous miscarriage and livebirth were similar between the two groups, while the pregnancy rate was significantly reduced in the L group compared with the H group. Further analysis indicated that the higher pregnancy rate of women in the H group may be due to more top embryos transferred per cycle. Due to an extremely low implantation potential for transfer of non-top embryos from WAA (= > 37 years old) in our reproductive centre, we assumed that all the embryos that implanted may result from the transfer of top embryos. Based on this observation, we found that the ratio of embryos that successfully implanted or eventually led to a livebirth to top embryos transferred was similar between the H and the L groups. Furthermore, women with clinical pregnancy or livebirth in the H or L group did not show a higher level of serum AMH but were younger than women with non-pregnancy or non-livebirth. Taken together, this study showed that AMH had a limited role in predicting in vitro embryo developmental potential and had no role in predicting the in vivo embryo developmental potential, suggesting that in WAA, AMH should not be used as a marker of oocyte quality. This study supports the view that the accumulation of top embryos via multiple oocyte retrieval times is a good strategy for the treatment of WAA.

Alkylating agents (AAs) that are commonly used for cancer therapy cause great damage to the ovary. Pyrroloquinoline-quinine (PQQ), which was initially identified as a redox cofactor for bacterial dehydrogenases, has been demonstrated to benefit the fertility of females. The aim of this study was to investigate whether PQQ dietary supplementation plays a protective role against alkylating agent-induced ovarian dysfunction. A single dose of busulphan (20 mg/kg) and cyclophosphamide (CTX, 120 mg/kg) were used to establish a mouse model of ovarian dysfunction. Feed containing PQQNa₂ (5 mg/kg) was provided starting 1 week before the establishment of the mouse model until the date of sacrifice. One month later, estrous cycle period of mice were examined and recorded for consecutive 30 days. Three months later, some mice were mated with fertile male mice for fertility test. The remaining mice were sacrificed to collect serum samples and ovaries. One day before sacrifice, some mice received a single injection of BrdU to label proliferating cells. Serum samples were used for test hormonal levels. Ovaries were weighted and used to detect follicle counts, cell proliferation, cell apoptosis and cell senescence. In addition, the levels of inflammation, oxidative damage and Pgc1α expression were detected in ovaries. Results showed that PQQ treatment increased the ovarian weight and size, partially normalized the disrupted estrous cycle period and prevented the loss of follicles of mice treated with AAs. More importantly, we found that PQQ treatment significantly increased the pregnancy rate and litter size per delivery of mice treated with AAs. The protective effects of PQQ appeared to be directly mediated by promoting cell proliferation of granulosa, and inhibiting cell apoptosis of granulosa and cell senescence of ovarian stromal cells. The underlying mechanisms may attribute to the anti-oxidative stress, anti-inflammation and pro-mitochondria biogenesis effects of PQQ.Our study highlights the therapeutic potential of PQQ against ovarian dysfunction caused by alkylating agents.

Intervertebral disk degeneration (IDD) is a major cause of low back pain that becomes a prevalent age‐related disease. However, the pathophysiological processes behind IDD are rarely known. Here, we used bioinformatics analysis based on the microarray datasets (GSE34095) to identify the differentially expressed genes (DEGs) as biomarkers and therapeutic targets in degenerated discs. From the previous studies, oxidative stress has been notified as a positive inducement of IDD, which causes DNA damage and accelerates cell senescence. Polyamine oxidase (PAOX), a member of the observed 1057 DEGs, is involved in polyamine metabolism and influences the oxidative balance in cells. However, it is uncertain if the IDD is implicated in the dysregulation of PAOX and polyamine metabolism. This study firstly verified the PAOX upregulation in human degenerated disc samples and applied an IL‐1β‐induced nucleus pulposus (NP) cell degeneration model to demonstrate that spermidine supplementation balanced polyamine metabolism and delayed NP cell senescence. Moreover, we confirmed that spermidine/N‐acetylcysteine supplementation or Cdkn2a gene deletion stabilized the polyamine metabolism, suppressed oxidative stress, and therefore delayed the progress of IDD in older mice. Collectively, our study highlights the role of polyamine metabolism in IDD and foresees spermidine would be the advanced therapeutical drug for IDD.