The expression changes of transcription factors including ANKZF1, LEF1, CASZ1, and ATOH1 as a predictor of survival rate in colorectal cancer: a large-scale analysis.

INTRODUCTION: Transcription factors (TFs) are essential for many biological processes and regulate the expression of several genes. This study's objective was to analyze the abnormalities in TF expression, their impact on patient prognosis, and related pathways in colorectal cancer (CRC). METHOD: The expression alterations of all TFs were investigated using the cancer genome atlas and GSE39582 data. Clinical data were also used to study the association between TFs expression and patient prognosis through the Cox regression test, and a predictive model of CRC patient survival was constructed based on TFs expression. Co-expression network was used to discover TF-related pathways. To validate the findings, the RT-qPCR method was applied to CRC samples and adjacent normal tissue. RESULTS: The findings revealed that ANKZF1, SALL4, SNAI1, TIGD1, LEF1, FOXS1, SIX4, and ETV5 expression levels increased in both cohorts and were linked to the poor prognosis. NR3C2, KLF4, CASZ1, FOXD2, ATOH1, SALL1, and RORC expression, on the other hand, exhibited a significant decrease, and their increase was related to the good prognosis of patients. The patient mortality risk model based on expression of mentioned TFs revealed that, independent of clinical characteristics, the expression of ANKZF1, LEF1, CASZ1, and ATOH1 could accurately predict patient survival rates. According to the co-expression network, increased transcription factors were linked to metastatic pathways, while decreasing TFs were involved to apoptotic pathways. RT-qPCR findings showed that FOXS1 expression was markedly overexpressed in CRC samples. However, in CRC samples, the expression of CASZ1 decreased. CONCLUSION: In CRC, TFs expression of ANKZF1, LEF1, CASZ1 and ATOH1 are deregulated, which are associated with prognosis in patients. According to our findings, changes in the expression of the mentioned TFs have the potential to be considered diagnostic and prognostic biomarkers for CRC patients.

Retraction Note to: Immobilization of lactoperoxidase on ZnO nanoparticles with improved stability.

The Editors have retracted this article [1] because significant parts of the text were duplicated from previously published articles by Ziyae et al. 2019 [2], Movahedi et al. 2019 [3] and Ziyae et al. 2018 [4]. The authors have not responded to any correspondence regarding this retraction.

Immobilization of lactoperoxidase on ZnO nanoparticles with improved stability.

OBJECTIVES: The study aimed to develop a facile and effectual method to enhance the stability of lactoperoxidase (LPO) by immobilizing it on ZnO Nanoparticles (ZnO NPs). RESULTS: The successful immobilization of LPO on ZnO NPs was confirmed by using Fourier transform infrared spectroscopy (FT-IR) and field emission scanning electron microscopy (FE-SEM). The Km values of free LPO and LPO immobilized on ZnO were 53.19, 89.28 mM and their Vmax values were 0.629, 0.46 µmol/mL min, respectively. The overall results showed that the stability of the immobilized LPO was significantly improved compared to free LPO. The LPO immobilized on ZnO (LPO-ZnO) retained 18% of the initial activity within 30 days at 25 °C whereas the free enzyme lost its activity after 7 days at the same temperature. Moreover, evaluation of the thermal stability of LPO at 75 °C determined the conservation of 12% of the initial activity of LPO in the LPO-ZnO sample after 60 min whereas the free enzyme lost its activity after 5 min. CONCLUSIONS: According to the present results, ZnO nanoparticles are suitable for the immobilization of LPO.

Immobilization of lactoperoxidase on Fe3O4 magnetic nanoparticles with improved stability.

OBJECTIVE: The study aimed to develop a facile and effectual method to increase the stability of lactoperoxidase (LPO) by using its immobilization on Fe3O4 magnetic nanoparticles (Fe3O4 MNPs). RESULTS: The successful immobilization of LPO on Fe3O4 MNPs was confirmed by using Fourier transform infrared spectroscopy (FT-IR) and field emission scanning electron microscopy (FE-SEM). The Km values of free LPO and LPO immobilized on Fe3O4 were 53.19, 72.46 mM and their Vmax values were 0.629, 0.576 µmol/mL min respectively. The overall results indicated that the stability of the immobilized LPO was significantly improved compared to free LPO. The LPO immobilized on Fe3O4 (LPO- Fe3O4) retained 28% of the initial activity within 30 days at 25 °C whereas the free enzyme lost its activity after 7 days at the same temperature. Moreover, evaluation of the thermal stability of LPO at 75 °C determined the conservation of 19% of the initial activity of LPO in the LPO- Fe3O4 sample after 60 min whereas the free enzyme lost its activity after 5 min. CONCLUSIONS: According to the present results, Fe3O4 magnetic nanoparticles are suitable for the immobilization of LPO.

Polymorphisms in CD14 Gene May Modify Soluble CD14 Levels and Represent Risk Factors for Multiple Sclerosis.

BACKGROUND: Besides the central role of the adaptive immune system, a disturbance of innate immune system is also suggested to be involved in the pathogenesis of multiple sclerosis (MS). CD14, a receptor upregulated in activated microglia, is known to be an essential mediator of inflammation in innate immune responses. Therefore, in this study we aimed to assess possible roles of CD14-159 and -260 gene polymorphisms in MS susceptibility and the effects of those polymorphisms to its protein producing capacity in Iranian population. METHODS: In this case control study, CD14-159 and -260 polymorphisms were genotyped using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP) in 200 MS patients and 200 healthy controls matched in age and gender. Serum levels of soluble CD14 (sCD14) was determined by enzyme-linked immunosorbent assay (ELISA). RESULTS: There were significant differences in genotype distribution of CD14-159 and -260 polymorphisms between patients and controls (P = 0.01, for-both). Mean serum level of sCD14 was significantly higher in MS patients than in control subjects (3340.30 ± 612.50 ng/ml vs 2353.73 ± 539.07 ng/ml; P < 0.01). CONCLUSION: In summary, we conclude that CD14-159 and -260 polymorphisms are associated with the risk of MS in Iranian population and affects CD14 promoter activity, thereby regulating CD14 expression. Furthermore, our study provides preliminary evidence for the activation of innate immunity in the pathogenesis of MS. In addition, the findings of the present study suggest serum level of sCD14 as candidate biomarker of MS severity.

The normoglycemic first-degree relatives of patients with type 2 diabetes mellitus have low circulating omentin-1 and adiponectin levels.

OBJECTIVE: It has been suggested that adipose-derived cytokines act as insulin sensitizers/insulin-mimetics and some others may induce insulin resistance. In order to elucidate the potential role of novel adipocytokines in the pre-diabetes states, circulating levels of novel adipocytokines were evaluated in first-degree relatives of subjects with type 2 diabetes mellitus (FDRs). METHOD: Serum omentin-1, adiponectin and retinol-binding protein 4 (RBP4) levels were measured in 179 subjects (90 glucose tolerant FDRs and 89 age- and sex-matched healthy controls) using enzyme-linked immunosorbent assay (ELISA) methods. RESULTS: There was no significant difference between the two groups regarding serum RBP4 concentrations. However, serum omentin-1 (median [interquartile range], 6.18 [4.06-11.52]ng/ml versus 10.50 [4.30-20.60]ng/ml, p=0.004) and adiponectin (mean±SD, 10.07±4.0 µg/ml versus 20.66±8.12 µg/ml, p<0.0001) levels were significantly lower in FDRs when compared with the controls. In multiple logistic regression analysis, FDRs showed a significant association with lower circulating omentin-1 and adiponectin levels, even after adjustments were made for age, sex, body mass index, blood pressure measures, and biochemical parameters including glucose status, lipid profile, insulin levels and HOMA-IR (OR=0.49, CI [0.30-0.79]; p=0.004 and OR=0.74, CI [0.67-0.82]; p<0.0001, respectively). However, FDRs did not show a significant association with serum RBP4 levels in different models of regression analyses. CONCLUSIONS: The FDRs showed significant associations with lower omentin-1 and adiponectin levels. A potential role for these adipokines in the FDRs' increased risk of diabetes needs to be further elucidated.

Green Synthesis of Magnetic Nanoparticles Using Satureja hortensis Essential Oil toward Superior Antibacterial/Fungal and Anticancer Performance.

The biological synthesis of nanoparticles, due to their environmental and biomedical properties, has been of particular interest to scientists and physicians. Here, iron nanoparticles (FeNPs) were synthesized using Satureja hortensis essential oil. Then, the chemical, functional, and morphological properties of these nanoparticles were characterized by typical experiments such as Uv-Vis, FTIR, XRD, FE-SEM, PSA, zeta potential, EDX, and EDX mapping. The results indicated Fe nanoparticles' formation with a cubic morphological structure and a particle size in the range of 9.3-27 nm. The antimicrobial effects of these nanoparticles were further evaluated using disc diffusion, minimum inhibitory concentration (MIC), minimum bactericidal concentration (MBC), and minimum fungal concentration (MFC) against two gram-positive bacterial strains (Staphylococcus aureus and Corynebacterium glutamicum), two gram-negative bacterial strains (Pseudomonas aeruginosa and Escherichia coli), and one fungus species Candida albicans. The results showed that green-synthesized Fe nanoparticles possessed higher antimicrobial properties than Satureja hortensis essential oil against selected pathogenic microorganisms, especially Gram-negative bacteria. Finally, the anticancer effect of these Fe nanoparticles was investigated on human cancer cells, K-562, and MCF-7, by the MTT assay. The results showed the anticancer effect of these nanoparticles against selected cell lines.

Toxicity and protein composition of venoms of Hottentotta saulcyi, Hottentotta schach and Androctonus crassicauda, three scorpion species collected in Iran.

BACKGROUND: Scorpion stings comprise a serious problem throughout the globe, especially in regions where they are more frequent. Despite a recent upsurge of interest in scorpion venoms by various research groups, there remain many challenges. OBJECTIVE: Therefore, in this study, we aimed to study the toxicity and protein composition of venoms of Hottentotta saulcyi, Hottentotta schach and Androctonus crassicauda, three scorpion species collected in Iran. MATERIALS AND METHODS: Scorpion species were collected from Esfahan farm scorpion company and maintained in the laboratory in containers that mimic their natural habitat. Venom was extracted from A. crassicauda, H. schach and H. saulcyi by electrical stimulation of 8 and 10 V. The toxicity of each venom was established by using four groups of male Swiss albino mice aged 2 months (weighting 18-20 g) for testing each dose of venom. One group was used as a control. Venom was injected into mice by subcutaneous route. Then, animals were monitored for 24 h and LD50 was estimated by the graphic method of Miller and Tainter. Thus, high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS) method was used to determine amino acids in the venom, and protein concentrations were determined by the Biuret method. RESULTS: LD50 of scorpion venoms by subcutaneous route was found to be 1.70 mg/kg b.w (A. crassicauda), 1.47 mg/kg b.w (H. saulcyi) and 0.85 mg/kg b.w (H. schach). A. crassicauda, H. saulcyi and H. schach contain 26, 30, and 31 amino acids, respectively. A. crassicauda contains low concentrations of alpha-aminoadipic acid, beta-aminoisobutyric acid, beta-alanine and citrulline. H. saulcyi contains a concentration of hydroxylysine, whereas H. schach has no such concentration. A. crassicauda also had the highest levels of tyrosine and threonine. Only A. crassicauda venom contains a low proportion of proteins (14.80%) compared with those of H. schach (16.26%) and H. saulcyi (16.20%). Albumin content in the venoms was 11.7% (H. saulcyi), 5.4% (H. schach) and 4.4% (A. crassicauda). CONCLUSION: Scorpions venoms have a variable toxicity and an interesting composition in amino acids and proteins. Work on the development of anti-venom is fundamental.

Methylenetetrahydrofolate reductase gene polymorphism in diabetes and obesity.

Methylenetetrahydrofolate reductase (MTHFR) polymorphism may play an important role in the pathophysiology of obesity and diabetes accompanied by obesity due to its influence on plasma homocysteine levels. There are significant and sometimes very strong relationship between levels of homocysteine and several multi-system diseases including CHD and CVA. To examine the association between MTHFR gene C677T polymorphism in diabetes and obesity with serum homocysteine levels. A total of 682 subjects were recruited in four groups (Normal, obese, diabetic and obese and diabetics). MTHFR gene C677T polymorphism was detected using PCR-RFLP technique. Serum homocysteine levels were measured using HPLC. There was a significant increase in the mean serum homocysteine levels in subjects carrying TT genotype (34.6 +/- 26.5) compared to subjects carrying CC (15.1 +/- 8) or CT genotype (16.4 +/- 7.8) (P < 0.000). We found no significant differences for MTHFR allele and genotype frequencies between different groups. Our data have confirmed the association between serum homocysteine levels and MTHFR C677T genotype reported in other populations.

Amyloid Nano-biofibrils as a New Nano-Scaffold for Lipase Immobilization.

BACKGROUND: Amyloids could be created under destabilizing conditions from various proteins. Having high chemical reactive groups makes the amyloid fibers suitable for enzyme stabilization. Imobilization of lipase as one of the stable classes of high catalytic power enzymes could be very valuable. OBJECTIVE: In the present study, the lipase from Pseudomonas cepacia was immobilized on BSA amyloid nano-biofibrils and the kinetic parameters were compared with those of its free counterpart. The possibility of using this nano-material as a new nano-scaffold for lipase immobilization was investigated. METHOD: Response surface methodology was used in this study to produce the maximum amounts of amyloid fibrils using Design Expert 7 software. Transmission electron microscopy was employed to confirm the presence of amyloid fibers. The stabilization process was performed by glutaraldehyde mediated covalent cross-links between the enzyme and amyloid fibers. Kinetic parameters including activity, specific activity, optimal pH and temperature and thermal stability of immobilized enzyme were compared with the free counterpart. RESULTS: The optimum conditions for fibrillogenesis were obtained at 4.36 mg.ml-1 of protein after 72 hours of mild agitation in a mixed citrate-phosphate buffer at the pH of 4.5 and the temperature of 80 ºC. The kinetic parameters of the immobilized lipase were improved in terms of activity, specific activity, Km and Vmax, optimal pH and temperature and thermal stability at 40 ºC. Amyloid fibrils with a diameter of less than 100 nm, as a new nano-scaffold, increased both the stability of lipase and other kinetic properties of the enzyme. CONCLUSION: Amyloid fibrils as a new chemically-rich nano-scaffold could be an appropriate matrix for lipase immobilization.

Hepatoprotective effects of Berberis vulgaris leaf extract on carbon tetrachloride-induced hepatotoxicity in rats.

INTRODUCTION: Hepatic sickness is a serious problem for human health. The researchers are interested in using medicinal plants including barberry to cure many of these sicknesses. In this study, the effect of hydroalcoholic extract of Berberis vulgaris leaf on hepatic protection was assessed in rats. MATERIALS AND METHODS: Forty healthy male Wistar rats were divided randomly into five groups (n = 8): Group 1 (healthy control), intraperitoneal injection of olive oil; Group 2 (hepatotoxic control), intraperitoneal injection of carbon tetrachloride and daily gavage of distilled water; and testing groups, intraperitoneal injection of carbon tetrachloride along with daily gavage of B. vulgaris leaf extract 40, 80, and 120 mg/kg of weight, respectively. After 6 weeks, the following were checked: enzyme level of alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), as well as serum level of total protein (TP), albumin (ALB), and histopathological status of the liver. RESULTS: The level of AST, ALP, and ALT was increased to 109 (IU/L), 95(IU/L), and 71(IU/L), respectively, in hepatotoxic control group than healthy control group, and there was a decrease of 0.86 (g/dl) and 0.04 (g/dl) in TP and ALB levels, respectively. The B. vulgaris extract in every three doses caused a significant decrease in hepatic enzymes level. However, the TP had a significant increase in 80 and 120 mg/kg of body weight. Regarding ALB, there was no significant difference among these groups. The histopathological results were not conformed to biochemical findings. CONCLUSION: Using the appropriate dose of B. vulgaris leaf extract can help the improvement of laboratory symptoms of fatty liver.

Concentration of lead and mercury in collected vegetables and herbs from Markazi province, Iran: a non-carcinogenic risk assessment.

The current study was undertaken to determine the concentration of Hg and Pb in ten types of collected green leafy vegetables and herbs from different agricultural sites of Markazi province, Iran as well as the gathered water and soil around them using inductively coupled plasma-optical emission spectroscopy (ICP-OES). Also, the potential health risk assessment by using target hazard quotient (THQ) and hazard index (HI) parameters was estimated. Based on the accumulation order, Artemisia dracunculus L with 56.147 ±â€¯17.30 µg/kg and Spinacia oleracea L with 1733.62 ±â€¯2264.7 µg/kg can uptake and accumulate more concentration of Pb and Hg in their tissues, respectively. Regarding gathered soil around vegetables, the concentration of Hg and Pb were measured as 52.056 ±â€¯16.25 µg/kg and 4993.83 ±â€¯1287.8 µg/kg, respectively. The transfer factor (TF) demonstrated that vegetables and herbs could absorb a high amount of Hg from the soil while these plants uptake less concentration of Pb thought their green leaves. The non-carcinogenic risk assessment showed the minimum, and maximum THQ was related to 15-24 and 35-44 age groups in the urban and rural consumers. Also, HI in the urban and rural areas was calculated as 8.492 and 9.012, respectively. Since HI > 1, exposure of the urban and rural areas of Markazi province to non-carcinogenic risk by consuming the green leafy vegetables and herbs is a source of concern.

Aqueous extract of Launaea acanthodes induces glutamate uptake and GABA release in astrocyte cell culture via a ROS scavenging mediated process.

Launaea acanthodes is extensively used in the semiarid region of Iran for treatment of seizure. However, the underlying mechanism has not been studied well. In our previous study we showed that Launaea acanthodes extract could effectively stimulate GABA release from PC12 cell culture. The critical role of astrocytes in epileptic brain in regulation of neurotransmitter balance in central nervous system encouraged us to investigate the effect of Launaea acanthodes extract on GABA and glutamate release from astrocytes. Our results indicated that LA extract could stimulates both glutamate uptake and GABA release by astrocytes. The results confirmed this fact that GABA release by astrocytes in response to LA treatment is a glutamate uptake-dependent process. We showed that stimulation of GABA release by Launaea acanthodes is a gene expression based process which depends on glutamate uptake. We propose that glutamate uptake via glutamate transporter 3 could activate expression of glutamate decarboxylase which in turn transforms uptaken glutamate into GABA.

Molecular detection of aminoglycoside-modifying enzyme genes in Acinetobacter baumannii clinical isolates.

Acinetobacter baumannii is a major opportunistic pathogen in healthcare settings worldwide. In Iran, there are only few reports on the prevalence of aminoglycoside resistance genes among A. baumannii isolates. The aim of this study was to investigate the existence of aminoglycoside-modifying enzyme (AME) genes from A. baumannii strains collected at a university teaching hospital in Iran. One hundred A. baumannii strains were collected between 2014 and 2015 from hospitalized patients at Loghman Hakim Hospital, Tehran, Iran. Antimicrobial susceptibility was determined by disk diffusion method according to the Clinical and Laboratory Standards Institute recommendations. The DNA was extracted using a kit obtained from Bioneer Co. (Korea) and was used as a template for polymerase chain reaction. The most active antimicrobial agent against these strains was colistin. The rate of extended-spectrum cephalosporin resistance was 97%. The aadA1, aadB, aac(6')-Ib, and aac(3)-IIa genes were found in 85%, 77%, 72%, and 68% of A. baumannii isolates, respectively. This study showed a high prevalence rate of AME genes in A. baumannii. This prevalence rate has explained that further aminoglycoside resistance genes may have role in the resistance of clinical isolates of A. baumannii. Therefore, control and treatment of serious infections caused by this opportunistic pathogen should be given more consideration.

Anti-proliferative and apoptotic effects of Ziziphus Jujube on cervical and breast cancer cells.

OBJECTIVE: Ziziphus Jujube (Jujube) plant has exhibited numerous medicinal and pharmacological properties including antioxidant and anti-inflammatory effects. This study was carried out to investigate its anti-cancer and pro-apoptotic abilities in human cervical and breast cancer cells in vitro. MATERIALS AND METHODS: The cervical OV2008 and breast MCF-7 cancer cells were incubated with different concentrations of Jujube aqueous extraction (0-3 mg/ml) for various times (0-72 h). Cell viability was assessed by Trypan Blue and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The expression of two apoptosis-related genes in treated cells evaluated by quantitative Real Time -PCR analysis. RESULTS: Jujube significantly inhibited cancer cell viability in a dose- and time- dependent manner. Herb-induced apoptosis was associated with enhanced expression of Bax and decreased Bcl2 gene leading eventually to a time-dependent six fold increase in the Bax/Bcl-2 ratio. CONCLUSION: These results indicated that Jujube may be a natural potential and promising agent to prevent or treat human cancers.

In-syringe reversed dispersive liquid-liquid microextraction for the evaluation of three important bioactive compounds of basil, tarragon and fennel in human plasma and urine samples.

In the present study, an efficient and environmental friendly method (called in-syringe reversed dispersive liquid-liquid microextraction (IS-R-DLLME)) was developed to extract three important components (i.e. para-anisaldehyde, trans-anethole and its isomer estragole) simultaneously in different plant extracts (basil, fennel and tarragon), human plasma and urine samples prior their determination using high-performance liquid chromatography. The importance of choosing these plant extracts as samples is emanating from the dual roles of their bioactive compounds (trans-anethole and estragole), which can alter positively or negatively different cellular processes, and necessity to a simple and efficient method for extraction and sensitive determination of these compounds in the mentioned samples. Under the optimum conditions (including extraction solvent: 120 µL of n-octanol; dispersive solvent: 600 µL of acetone; collecting solvent: 1000 µL of acetone, sample pH 3; with no salt), limits of detection (LODs), linear dynamic ranges (LDRs) and recoveries (R) were 79-81 ng mL(-1), 0.26-6.9 µg mL(-1) and 94.1-99.9%, respectively. The obtained results showed that the IS-R-DLLME was a simple, fast and sensitive method with low level consumption of extraction solvent which provides high recovery under the optimum conditions. The present method was applied to investigate the absorption amounts of the mentioned analytes through the determination of the analytes before (in the plant extracts) and after (in the human plasma and urine samples) the consumption which can determine the toxicity levels of the analytes (on the basis of their dosages) in the extracts.

The potential role of APOBEC3G in limiting replication of hepatitis B virus.

BACKGROUND AND STUDY AIMS: Recent findings introduced APOBEC3G (A3G) as a host factor that blocks viral replication. It induces G to A hypermutations in viral DNA at the step of reverse transcription and in response to interferon. This study aimed to investigate the expression of liver A3G protein in association with both replication of hepatitis B virus (HBV) and frequency of G to A mutations in BCP (basal core promoter)-PC (pre-core) region. PATIENTS AND METHODS: Fifty-one liver biopsies of naïve chronic hepatitis B (CHB) patients enrolled for the expression of A3G were done by immunohistochemistry (IHC) standard method. The presence of HBV DNA and sequences of BCP-PC region at the time of liver biopsy was investigated in all patients. RESULTS: Among 34 patients with detectable HBV DNA, 31 carried 1-5 G to A mutations in the BCP-PC region. IHC results showed that the expression level of A3G in CHB patients' liver was very low. Of all patients, A3G is expressed in three undetectable HBV DNA subjects and a patient with 2.24×10(4) copies ml(-1) of HBV DNA. G to A mutated residues were indicated at positions 1727, 1757 and 1896 of the HBV genome of this patient. CONCLUSION: This study indicates that despite very low levels of both A3G in liver and the number of positive subjects, A3G has a potential role to restrict the in vivo replication of HBV.

Decreased adiponectin levels in polycystic ovary syndrome, independent of body mass index.

BACKGROUND: Insulin resistance has been shown to have an association with polycystic ovary syndrome (PCOS). This study was designed to evaluate the potential role of adiponectin, which is linked with insulin resistance, in the etiology of PCOS and its relationship to obesity. METHODS: This case-control study consisted of 103 newly diagnosed PCOS cases and 73 female controls seen at a referral university hospital in Zanjan, Iran. Serum adiponectin, insulin, plasma fasting glucose, and lipid levels were measured. The homeostasis model assessment index was used to determine the level of insulin resistance. Women were classified as follows: Group I (normal nonlean women); group II (normal lean women); group III (nonlean women with PCOS); and group IV (lean women with PCOS) RESULTS: Adiponectin levels were decreased in women with PCOS (8.4 +/- 2.7 ng/mL vs. 13.6 +/- 5 ng/mL in the control group, P < 0.001). There was no significant difference between the adiponectin concentrations of women in group III and that in group IV (8.1 +/- 2.8 ng/mL vs. 9.2 +/- 2.6 ng/mL, respectively, P = 0.1). Adiponectin levels were significantly lower in group I compared with group II. A weak but significant negative correlation was found between adiponectin and insulin levels in all the subjects. Multiple regression analyses showed that the presence of PCOS was the only significant determinant of serum adiponectin levels. CONCLUSIONS: Adiponectin levels were reduced in all the women with PCOS. There seemed to be an interaction between adiponectin and PCOS pathogenesis that was independent of body mass index.