Targeting prostate cancer with docetaxel-loaded peptide 563-conjugated PEtOx-co-PEI30%-b-PCL polymeric micelle nanocarriers.

Prostate cancer is a global disease that negatively affects the quality of life. Although various strategies against prostate cancer have been developed, only a few achieved tumor-specific targeting. Therefore, a special emphasis has been placed on the treatment of cancer using nano-carrier-encapsulated chemotherapeutic agents conjugated with tumor-homing peptides. The targeting strategy coupling the drugs with nanotechnology helps to overcome the most common barriers, such as high toxicity and side effects. Prostate-specific membrane antigen has emerged as a promising target molecule for prostate cancer and shown to be targeted with high affinity by GRFLTGGTGRLLRIS peptide known as peptide 563 (P563). Here, we aimed to assess the in vitro and in vivo targeting efficiency, safety, and efficacy of P563-conjugated, docetaxel (DTX)-loaded polymeric micelle nanoparticles (P563-PEtOx-co-PEI30%-b-PCL-DTX) against prostate cancer. To this end, we analyzed the cytotoxic activity of P563-PEtOx-co-PEI30%-b-PCL and P563-PEtOx-co-PEI30%-b-PCL-DTX by a cell proliferation assay using PNT1A and 22Rv1 cells. We have also determined the targeting selectivity of P563-PEtOx-co-PEI30%-b-PCL-FITC by flow cytometry and assessed the induction of cell death by western blot and TUNEL assays for P563-PEtOx-co-PEI30%-b-PCL-DTX in 22Rv1 cells. To investigate the in vivo efficacy, we administered DTX in the free form or in polymeric micelle nanoparticles to athymic CD-1 nu/nu mice 22Rv1 xenograft models and performed histopathological analyses. Our study showed that targeting prostate cancer with P563-conjugated PEtOx-co-PEI30%-b-PCL polymeric micelles could exert a potent anti-cancer activity with low side effects.

Mild and Functional Group-Tolerant Aerobic N-Dealkylation of Tertiary Amines Promoted by Photoredox Catalysis.

This article describes the development of a mild method for the N-dealkylation of tertiary amines via photoredox catalysis and its application in late-stage functionalization. Using the developed method, more than 30 diverse aliphatic, aniline-type, and complex substrates are shown to undergo N-dealkylation, providing a method with broader functional group tolerance compared to methods found in the literature. The scope also includes tertiary and secondary amine molecules with complex substructures and drug substrates. Interestingly, α-oxidation to imines was observed in several cyclic substructures instead of N-dealkylation, suggesting that imines are relevant reaction intermediates.

Synthesis of Schiff Bases and Secondary Amines with Indane Skeleton; Evaluation of Their Antioxidant, Antibiotic, and Antifungal Activities.

In this study, Schiff bases were synthesized by utilizing the reaction of 4- and 5-aminoindane with substituted benzaldehydes. After the reduction of isolated Schiff bases with NaBH4 , the corresponding secondary amine derivatives were obtained. The structures of all synthesized molecules were confirmed by 1 H-NMR, 13 C-NMR, FT-IR, and ESI-MS. Antioxidant activities of all synthesized molecules were investigated by DPPH method, and IC50 values were calculated. In addition, antibacterial activities of targets were investigated by the well diffusion method, and then MIC99 values were calculated. While only four of the sixteen synthesized molecules showed a high level of antioxidant activity, all of the molecules exhibited biological activity against Gram-positive and Gram-negative bacteria to varying degrees. In addition, all the synthesized molecules showed high antifungal activity. In antioxidant capacity studies, the IC50 values of 2-(((2,3-dihydro-1H-inden-5-yl)amino)methyl)-6-methoxyphenol (4 d) and 2-(((2,3-dihydro-1H-inden-4-yl)amino)methyl)-6-methoxyphenol (7 d) were determined to be 18.1 µg and 35.1 µg, respectively, and these values are much stronger than BHT (butylated hydroxytoluene) and BHA (butylated hydroxyanisole) used as positive controls. The fact that targets have the same core structure with different substituents has revealed a good structure-activity relationship.

Simulation for breastfeeding support during the COVID-19 pandemic in Turkey: A quasi-experimental study.

We aimed to investigate the effect of simulation-supported breastfeeding program given to women in pregnancy during the COVID-19 pandemic period on breastfeeding success, breastfeeding self-efficacy, and mother-infant attachment. They carried out this study 73 pregnant women who presented to the obstetrics and gynecology clinic of a hospital and were selected by using the simple random sampling method. The researchers used a quasi-experimental design in this study. After the simulation-supported breastfeeding program, they found that breastfeeding success and breastfeeding self-efficacy were increased in the experimental group compared to the control group. The researchers were used the structural equation model, regression analysis, and independent samples t-test in the data analysis. The education given to pregnant women in this period when social interaction decreases becomes more important. Researchers are recommended that breastfeeding education should start in the antenatal period and continue in the postpartum period by using different education methods together. Simulation-supported breastfeeding program is a model that can be used to provide breastfeeding education for pregnant women in public health emergencies such as the COVID-19 pandemic. With this program, the number of visits to the hospital for breastfeeding education will decrease, and more remote counseling will be provided.

Hair tourniquet syndrome of toe.

INTRODUCTION: Hair tourniquet syndrome (HTS) is a rare surgical emergency caused by a hair or thread wrapping around an appendage. We aimed to present our clinical experience with HTS of toes and attract physicians' attention to this rare entity. METHODS: Between January 2012 and September 2022; 26 patients (25 pediatric and one adult case) were treated for HTS. All pediatric cases were treated surgically under loop magnification. The adult patient was treated nonsurgically. The patient's age, gender, affected appendage and side, duration of symptoms, and postoperative complications were recorded. RESULTS: Thirty-six toes of 25 patients (13 boys, 11 girls, and a male adult) were included in the study. The mean age of pediatric patients was 126.6 days. The third toe was the most affected (n:16), followed by the fourth (n:8). In seven patients more than one was affected. CONCLUSION: HTS should be treated as soon as possible when diagnosed to prevent further complications including appendage loss.

Attentional Modulation of Hierarchical Speech Representations in a Multitalker Environment.

Humans are remarkably adept in listening to a desired speaker in a crowded environment, while filtering out nontarget speakers in the background. Attention is key to solving this difficult cocktail-party task, yet a detailed characterization of attentional effects on speech representations is lacking. It remains unclear across what levels of speech features and how much attentional modulation occurs in each brain area during the cocktail-party task. To address these questions, we recorded whole-brain blood-oxygen-level-dependent (BOLD) responses while subjects either passively listened to single-speaker stories, or selectively attended to a male or a female speaker in temporally overlaid stories in separate experiments. Spectral, articulatory, and semantic models of the natural stories were constructed. Intrinsic selectivity profiles were identified via voxelwise models fit to passive listening responses. Attentional modulations were then quantified based on model predictions for attended and unattended stories in the cocktail-party task. We find that attention causes broad modulations at multiple levels of speech representations while growing stronger toward later stages of processing, and that unattended speech is represented up to the semantic level in parabelt auditory cortex. These results provide insights on attentional mechanisms that underlie the ability to selectively listen to a desired speaker in noisy multispeaker environments.

Turkish obstetricians' self-birth preferences, attitudes and practices towards caesarean section on maternal request and vaginal birth after caesarean section: a national online survey.

The aim of the study was to investigate the reasons for Turkish obstetricians having self-caesarean section on maternal request (CSMR) and their attitudes and practices related to CSMR and vaginal birth after caesarean section (VBAC). The questionnaire form constructed by the authors was sent online to obstetricians working in different cities of Turkey. A total of 206 obstetricians participated and answered a self-administered questionnaire. The self-birth preferences were as follows: 17% had a vaginal delivery (VD), 61.2% had a caesarean section (CS), 4.9% had both VD and CS. Of the participants with CS, 56.3% had CSMR. The most common reason for their having self-CSMR was that it was 'safe for the baby'. The most common reason for performing CSMR with their patients was 'due to birth anxiety and phobia'. Fifty-five percent of the participants said that they first recommended VD. The most common concern related to VBAC was 'I'm afraid of legal sanctions about complications'. Although many Turkish obstetricians recommend VD to their patients, they are afraid of the complaints/trials related to unforeseen complications during VD. IMPACT STATEMENTWhat is already known on this subject? Caesarean section (CS) rates all over the world and in Turkey are rising. The exact frequency of CS on maternal request (CSMR) is not known, but it is estimated to be between 4% and 18%.What do the results of this study add? Although Turkish obstetricians had high self-CSMR rates, they thought that it was more correct to direct patients to vaginal delivery (VD). Obstetricians are afraid of unforeseen complications during VD and related complaints and legal trials.What are the implications of these findings for clinical practice and/or further research? Physicians expect improvements in the judgement and punishment issues related to unforeseen complications in the birth process. Besides the actual rates of CSMR need to be reported in the literature and why obstetricians perform CSMR needs to be investigated globally.

Delivery of doxorubicin loaded P18 conjugated-poly(2-ethyl-oxazoline)-DOPE nanoliposomes for targeted therapy of breast cancer.

Breast cancer, a heterogeneous disease, has the highest incidence rate and is a major cause of death in females worldwide. Drug delivery by using nanotechnology has shown great promise for improving cancer treatment. Nanoliposomes are known to have enhanced accumulation ability in tumors due to prolonged systemic circulation. Peptide 18 (P18), a tumor homing peptide targeting keratin-1 (KRT-1), was previously shown to have high binding affinity towards breast cancer cells. In this study, we investigate the ability of P18 conjugated PEtOx-DOPE nanoliposomes (P18-PEtOx-DOPE) for the targeted delivery of doxorubicin to AU565 breast cancer model. Toxicology studies of PEtOx-DOPE nanoliposomes performed on normal breast epithelial cells (MCF10A), showed minimal toxicity. Doxorubicin delivery by P18-PEtOx-DOPE to AU565 cells induces cytotoxicity in a dose and time dependent manner causing mitotic arrest in G2/M phase at 24 h. Anti-cancer activity of P18-PEtOx-DOPE-DOX nanoliposomes on AU565 cells was detected by Annexin V/PI apoptosis assay. In terms of in vivo antitumor efficacy, P18-PEtOx-DOPE-DOX nanoliposomes administration to AU565 CD-1 nu/nu mice model showed significant decrease in tumor volume suggesting that DOX delivered by these nanoliposomes elicited a strong antitumor response comparable to the free delivery of doxorubicin. Overall, our results offered preclinical proof for the use of P18-PEtOx-DOPE-DOX nanoliposomes in KRT-1+ breast cancer therapy.

Synthesis and evaluation of tumor-homing peptides for targeting prostate cancer.

High toxicity caused by chemotherapeutic drugs and the acquisition of drug resistance by cancer cells are the major drawbacks in cancer therapy. A promising approach to overcome the posed barriers is conjugating tumor-homing peptides to drugs or nanocarriers. Such high-affinity peptides can specifically target surface markers overexpressed by cancer cells, ensuring a rapid and cancer-specific uptake of the drugs. Since prostate-specific membrane antigen (PSMA) is overexpressed by aggressive prostate cancer cells, targeting this surface protein with peptide conjugates can lead to the development of effective strategies against prostate cancer. In this study, we aimed to determine which PSMA-binding peptide among peptides 563, 562 and 9-mer, show the highest selectivity towards PSMA using 22Rv1 prostate cancer cells, a cell line with moderate PSMA levels. Tumor-homing peptides were synthesized by fluorenylmethoxycarbonyl-based solid-phase peptide synthesis (Fmoc-SPPS) strategy, and evaluated for their prostate cancer cell-specific targeting efficiencies by flow cytometry. Our results showed that the PSMA-binding capacity of peptide 563 was superior to those of 562, 9-mer, and 5-mer; therefore, can be utilized as a potent-targeting agent not only in the treatment of high PSMA positive but also moderate PSMA positive prostate cancer tumors.

Iron-Catalyzed α-C-H Cyanation of Simple and Complex Tertiary Amines.

This manuscript details the development of a general and mild protocol for the α-C-H cyanation of tertiary amines and its application in late-stage functionalization. Suitable substrates include tertiary aliphatic, benzylic, and aniline-type substrates and complex substrates. Functional groups tolerated under the reaction conditions include various heterocycles and ketones, amides, olefins, and alkynes. This broad substrate scope is remarkable, as comparable reaction protocols for α-C-H cyanation frequently occur via free radical mechanisms and are thus fundamentally limited in their functional group tolerance. In contrast, the presented catalyst system tolerates functional groups that typically react with free radicals, suggesting an alternative reaction pathway. All components of the described catalyst system are readily available, allowing implementation of the presented methodology without the need for lengthy catalyst synthesis.

Design and evaluation of peptide-18-targeted nanoliposomes constructed by poly(2-oxazoline)-DOPE for doxorubicin delivery.

AIMS: The aim of this study is to develop targeted nanoliposome formulations to provide efficient treatment for breast cancer. In this study, peptide 18-modified poly(2-ethyl-2-oxazoline)-dioleoylphosphatidylethanolamine (P18-PEtOx-DOPE), was synthesised to construct nanoliposomes. METHODS: Doxorubicin (DOX) was encapsulated into the nanoliposomes by ethanol injection method. Particle size and polydispersity index were measured by dynamic light scattering. Zeta potential was determined by electrophoretic laser Doppler anemometry. The shape of the nanoliposomes was examined by transmission electron microscope. Specific bindings of P18-PEtOx-DOPE nanoliposomes were demonstrated on AU565 cells by confocal microscopy and flow cytometry studies. RESULTS: DOX-loaded nanoliposomes with particle diameter of 150.00 ± 2.84 nm and PDI of 0.212 ± 0.013 were obtained. PEtOx-DOPE and PEtOx-DOPE nanoliposomes are non-toxic on HUVEC, HEK293 and hMSC cells for 48 h. Furthermore, P18-PEtOx-DOPE nanoliposomes demonstrated specificity towards AU565 cells with high binding affinity. CONCLUSIONS: As a result, DOX-loaded P18-PEtOx-DOPE nanoliposomes can serve as favourable candidates in breast cancer targeted therapy.

Informed feature regularization in voxelwise modeling for naturalistic fMRI experiments.

Voxelwise modeling is a powerful framework to predict single-voxel functional selectivity for the stimulus features that exist in complex natural stimuli. Yet, because VM disregards potential correlations across stimulus features or neighboring voxels, it may yield suboptimal sensitivity in measuring functional selectivity in the presence of high levels of measurement noise. Here, we introduce a novel voxelwise modeling approach that simultaneously utilizes stimulus correlations in model features and response correlations among voxel neighborhoods. The proposed method performs feature and spatial regularization while still generating single-voxel response predictions. We demonstrated the performance of our approach on a functional magnetic resonance imaging dataset from a natural vision experiment. Compared to VM, the proposed method yields clear improvements in prediction performance, together with increased feature coherence and spatial coherence of voxelwise models. Overall, the proposed method can offer improved sensitivity in modeling of single voxels in naturalistic functional magnetic resonance imaging experiments.

Exploiting ionisable nature of PEtOx-co-PEI to prepare pH sensitive, doxorubicin-loaded micelles.

AIMS: This study was conducted to evaluate block copolymers containing two different poly(ethyleneimine) (PEI) amounts, as new pH-sensitive micellar delivery systems for doxorubicin. METHODS: Micelles were prepared with block copolymers consisting of poly(2-ethyl-2-oxazoline)-co-poly(ethyleneimine) (PEtOx-co-PEI) and poly(ε-caprolactone) (PCL) as hydrophilic and hydrophobic blocks, respectively. Doxorubicin loading, micelle size, pH-dependent drug release, and in vitro cytotoxicity on MCF-7 cells were investigated. RESULTS: The average size of drug-loaded micelles was under 100 nm and drug loading was between 10.7% and 48.3% (w/w). pH-sensitive drug release was more pronounced (84.7% and 68.9% (w/w) of drug was released at pH 5.0 and pH 7.4, respectively) for the micelles of the copolymer with the lowest PEI amount. The cell viability of doxorubicin-loaded micelles which were prepared by the copolymer with the lowest PEI amount was 28-33% at 72 h. CONCLUSIONS: PEtOx-co-PEI-b-PCL micelles of this copolymer were found to be stable and effective pH-sensitive nano-sized carriers for doxorubicin delivery.

Spatially informed voxelwise modeling for naturalistic fMRI experiments.

Voxelwise modeling (VM) is a powerful framework to predict single voxel responses evoked by a rich set of stimulus features present in complex natural stimuli. However, because VM disregards correlations across neighboring voxels, its sensitivity in detecting functional selectivity can be diminished in the presence of high levels of measurement noise. Here, we introduce spatially-informed voxelwise modeling (SPIN-VM) to take advantage of response correlations in spatial neighborhoods of voxels. To optimally utilize shared information, SPIN-VM performs regularization across spatial neighborhoods in addition to model features, while still generating single-voxel response predictions. We demonstrated the performance of SPIN-VM on a rich dataset from a natural vision experiment. Compared to VM, SPIN-VM yields higher prediction accuracies and better capture locally congruent information representations across cortex. These results suggest that SPIN-VM offers improved performance in predicting single-voxel responses and recovering coherent information representations.

Serum levels of spexin are increased in the third trimester pregnancy with gestational diabetes mellitus.

Spexin is a peptide that is involved in energy homeostasis and its expression is influenced by altered glucose metabolism. Gestational diabetes mellitus (GDM) is associated with increased insulin resistance (IR) and pregnancy is a progressive insulin resistant state. We hypothesized that spexin may have an effect on the pathophysiology of GDM which further could help to identify the disease. The aim of this study was to investigate spexin levels in the third trimester pregnancies with GDM and healthy controls. Thirty-nine women with GDM and 39 healthy singleton pregnancies were enrolled in this case-control study. Serum spexin concentrations were measured and correlated to biochemical and clinical parameters. Serum spexin levels were significantly higher in women with GDM (3686.25 ± 348.37 vs. 3472.33 ± 293.93 pg/ml, p=.004). Spexin levels ​​did not differ significantly according to treatment modality. Moreover, spexin levels were significantly positively correlated with homeostasis model assessment of IR (HOMA-IR). Spexin levels were significantly higher in women with GDM and closely related to HOMA-IR in the third trimester pregnancy. This may help to better clarify the pathophysiological role of spexin in GDM.

Synthesis, molecular modeling, in vivo study, and anticancer activity of 1,2,4-triazole containing hydrazide-hydrazones derived from (S)-naproxen.

A new series of 1,2,4-triazole containing hydrazide-hydrazones derived from (S)-naproxen ( 7a-m) was synthesized in this study. The structures of these compounds were characterized by spectral (Fourier-transform infrared spectroscopy, 1 H-nuclear magnetic resonance (NMR), 13 C-NMR, and high-resolution electron ionization mass spectrometry) methods. Furthermore, molecular modeling of these compounds was studied on human methionine aminopeptidase-2. All synthesized compounds were screened for anticancer activity against three prostate cancer cell lines (PC3, DU-145, and LNCaP) using the 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium colorimetric method. Compound 7a showed the best activity against the PC3, DU-145 and LNCaP cancer cell lines with IC50 values of 26.0, 34.5, and 48.8 µM, respectively. Compounds 7b, 7k, and 7m showed anticancer activity against cancer cell lines PC3 and DU-145 with IC50 values of 43.0, 36.5, 29.3 µM and 49.8, 49.1, 31.6 µM, respectively. Compounds 7f and 7g showed anticancer activity against PC3 cells with IC50 values of 43.4 and 34.5 µM, respectively. To assess the biodistribution in mice of IRDye800, dye-labeled compound 7a or 100 µM of free dye was injected intravenously into the mice's tail. In vivo images were taken with in vivo imaging system spectrum device at 60, 120, 180, 240, 300, and 360 min after injection. At the end of 360 min, ex vivo studies were carried out to determine in which organs the dye was accumulated in the urogenital system. Ex vivo studies showed that the accumulation of compound 7a in the prostate is greater than that of the free dye, and it is concluded that compound 7a may be promising for the treatment of prostate cancer.

Photoredox-Catalyzed Cα-H Cyanation of Unactivated Secondary and Tertiary Aliphatic Amines: Late-Stage Functionalization and Mechanistic Studies.

This paper describes the development and mechanistic studies of a general, high-yielding amine Cα-H cyanation protocol via photoredox catalysis. Inexpensive NaCN is employed as the cyanide source and air is the external oxidant, resulting in mild and highly functional group tolerant conditions. Notably, efficient Cα-H cyanations of secondary and tertiary aliphatic amines and of complex, biologically active compounds (drugs) can be performed using the established methodology. Mechanistic studies suggest that the carboxylic acid additive has three effects: formation of a stabilizing hemiaminal intermediate, prevention of catalyst decomposition by protonating the substrate, and modulation of fluorescence quenching of the photoexcited catalyst species.

The relationship of urocortin-2 with insulin resistance patients having PCOS.

In this study, we aimed to compare the serum urocortin-2 (UCN2) levels in women with polycystic ovary syndrome (PCOS) and healthy women. Thirty-eight patients with PCOS and 41 healthy women were included in the study whose age and BMI matched. The fasting serum glucose, insulin, free testosterone, hs-CRP and UCN2 levels of the all participants were examined. HOMA-IR formula was used in order to calculate the insulin resistance. Circulating UCN2 levels were significantly elevated in women with PCOS compared with controls (142.93 ± 59.48 versus 98.56 ± 65.01 pg/ml, p = 0.002). FBG, serum insulin, hs-CRP and HOMA-IR levels were found to be increased in women with PCOS. There was a positive correlation between UCN2 and free-testosterone in only PCOS group (r = 0.235, p = 0.027). Multivariate logistic regression analyses revealed that the odds ratio for PCOS was 2.31 for patients in the highest quartile of UCN2 compared with those in the lowest quartile (OR = 2.31, 95% CI = 1.88-2.83, p=0.021). Multiple linear regression analysis revealed that HOMA-IR, hs-CRP and free-testosterone independently predicted UCN2 levels (p < 0.05). UCN2 levels were significantly higher in PCOS cases when compared to control group. UCN2 is thought to be effective on pathophysiology of PCOS by paracrine and autocrine pathways.

Comparison of umbilical cord ghrelin concentrations in full-term pregnant women with or without gestational diabetes.

PURPOSE: Ghrelin is a potent orexigenic peptide hormone secreted from the gastrointestinal tract that plays a crucial role in the regulation of lipids and glucose metabolism. Ghrelin also has links with fetal development and growth. Gestational diabetes mellitus (GDM) causes fetal macrosomia, but there is no available evidence of a relationship between ghrelin levels and birth weight in women with GDM. The purpose of this study is to investigate whether umbilical cord ghrelin concentrations are altered in full-term pregnant women with GDM compared to women without GDM and whether birth weight is correlated with ghrelin levels. MATERIALS AND METHODS: Sixty pregnant women with GDM and 64 healthy pregnant women without GDM were included in this cross-sectional study. Blood samples were drawn from the umbilical vein following birth. Ghrelin concentrations were measured using enzyme-linked immunosorbent assay (ELISA). RESULTS: Umbilical vein ghrelin levels were decreased in women with GDM (879.6 ± 256.1 vs. 972.2 ± 233.6 pg/ml in women without GDM, p=0.033), whereas birth weights were higher for babies in the GDM than in the non-GDM group (3448 ± 410 vs. 3308 ± 365 gr, respectively, p=0.046). Umbilical ghrelin levels were inversely correlated with birth weight (r=-0.765, p<0.001). Multiple regression analysis revealed that birth weight was independently and negatively associated with umbilical ghrelin levels (ß= -2.077, 95% CI=-2.652 to -1.492, p=0.002). CONCLUSIONS: Umbilical ghrelin levels were lower in GDM women. Birth weight was inversely associated with umbilical ghrelin levels. This association may be explained by a negative feedback mechanism between ghrelin and birth weight.

Elevated circulating levels of xenopsin-related peptide-1 are associated with polycystic ovary syndrome.

PURPOSE: This study was conducted to compare serum xenopsin-related peptide-1 (XP-1) levels in women with polycystic ovary syndrome (PCOS) and in healthy women and to determine the role of XP-1 levels in PCOS. METHODS: Forty patients with PCOS and 38 healthy women were included in the study and matched with age and body mass index. Fasting blood glucose, insulin, high sensitivity C-reactive protein (hs-CRP), XP-1 and total testosterone levels of all participants were measured. RESULTS: Serum XP-1 levels significantly increased in women with PCOS compared to the control group (6.49 ± 1.57 vs 5.29 ± 1.45 ng/ml, p = 0.001). Serum insulin, hs-CRP, HOMA-IR, total testosterone levels and waist circumference were higher in women with PCOS than in control group. High XP-1 levels were associated with PCOS after adjustment for potential confounders. Receiver operating characteristic (ROC) curve analysis confirmed that the area under ROC curves was 0.703 (95% CI 0.588-0.818, p < 0.002) for XP-1 levels. The optimal cut-off value of XP-1 for detecting PCOS was ≥5.87 ng/ml. CONCLUSIONS: Our results indicate that increased XP-1 levels were associated with PCOS after adjustment for potential confounders, which has been shown to be effective in the function of the insulin signaling pathway.