Can signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) be used as an indicator of endothelial dysfunction in acromegaly patients?

PURPOSE: Acromegaly is closely related to increased oxidative stress and endothelial dysfunction (ED). This study aimed to evaluate, for the first time in the literature, signal peptide-CUB-EGF domain-containing protein 1 (SCUBE-1) and endothelial nitric oxide synthase e(NOS) levels in the setting of acromegaly. METHOD: A total of 56 acromegaly patients and a control group composed of 30 healthy volunteers were included in this study. In the postoperative follow-up, patients were grouped as active or in-remission according to their GH and IGF-1 levels in oral glucose stimulation test (OGST). After detailed physical examination of acromegaly patients and the control subjects, 8-hour fasting blood samples were collected to evaluate biochemical parameters including lipid profile, anterior pituitary hormones, and SCUBE-1 and e(NOS) levels. RESULTS: Inactive and active acromegaly was noted in 78.6% and 21.4% of patients, respectively. The median (min-max) SCUBE-1 levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (1.6(0.4-2.4) and 1.8(1.1-2.5) vs. 0.4(0.2-1.0) ng/mL, respectively, p < 0.001 for each). The median (min-max) e(NOS) levels were significantly higher in the inactive acromegaly and active acromegaly groups than in the control group (132.7 (26.8-602.9) and 137.3 (69.7-488.7) vs. 83.9 (16.4-218.7) pg/mL, p = 0.018 and p = 0.048, respectively). We have also detected positive correlations of e(NOS) with leukocyte (r = 0.307, p = 0.021) and neutrophil counts (r = 0.309, p = 0.021). CONCLUSION: Our study revealed for the first time in literature that SCUBE-1 levels, being a novel marker for ED, were significantly higher in acromegaly patients than in control subjects. When supported with clinical studies, SCUBE-1can be used as an early indicator of endothelial damage in acromegaly patients.

Functional and biochemical improvement following total knee arthroplasty in early postoperative period.

OBJECTIVE: There are very few studies about total knee arthroplasty biomechanical and biochemical effects in the early postoperative period. The aim of this study was to investigate the effect of total knee arthroplasty on pain intensity, knee joint valgus angle, malalignment, functional status, knee joint position sense, and cytokine levels. METHODS: A total of 29 patients (female/male: 24/5) who underwent total knee arthroplasty were included in the late-stage knee osteoarthritis group, and 22 patients (female/male: 13/9) with grade 4 osteoarthritis were included in the early-stage knee osteoarthritis group. The visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index were used to evaluate the pain intensity and functional status. Alignment and knee position sense measurements were also calculated. Systemic venous blood samples were taken to evaluate the interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta cytokine levels. RESULTS: In the study group, there were positive improvements in pain intensity, functional status, valgus angle, malalignment, amount of joint position sense deviation at 70° knee flexion angle parameters, and interleukin-6 of patients at the postoperative 6th week compared to the preoperative period (p<0.05). The patients in the study group had similar or better results in pain intensity, functional status, valgus angle, malalignment, amount of joint position sense deviation at 35°, 55°, and 70° knee flexion angles parameters, and in interleukin-6, compared to the control group at postoperative 6th week. CONCLUSION: Total knee arthroplasty provides improvements in pain, function, valgus angle, joint position sense, and interleukin-6 in the early postoperative period.

circRNAs in drug resistance of breast cancer.

Breast cancer (BC) is the most common heterogeneous disease in women and one of the leading causes of cancer-related death. Surgery, chemotherapy, radiotherapy, hormone, and targeted therapy are the gold standards for BC treatment. One of the significant challenges during the treatment of BC represents resistance to chemotherapeutics, resistance that severely limits the use and effectiveness of the drugs used for BC treatment. Therefore, it is essential to develop new strategies to improve therapeutic efficacy. Circular RNAs (circRNAs) are a large group of non-coding RNAs that covalently form closed circular loops by joining their 5', and 3'; ends. Accumulating evidence suggests that circRNAs have a vital role in cancer development, progression, and BC resistance to chemotherapy. The purpose of this review is to discuss the biological properties of circRNAs, and how circRNAs induce resistance to conventional therapeutic anti-cancer drugs used in BC treatment, by emphasizing and summarizing the potential roles of circRNAs in mechanisms of drug resistance, such as drug efflux, apoptosis dysfunction, autophagy, and DNA damage repair. CircRNAs are associated with drug resistance via ATP-binding cassette (ABC) efflux transporters, while some others by inhibition of cell apoptosis, thus leading to resistance to tamoxifen in BC cells. In contrast, others are involved in the promotion of BC cells chemoresistance by doxorubicin-induced autophagy. CircRNAs may have clinical significance in regulating or overcoming BC drug resistance and may give directions towards a novel approach to personalized BC treatment. CircRNAs may significantly contribute to the identification of new therapeutic targets for the prevention of BC chemoresistance.

Irisin ameliorates male sexual dysfunction in paroxetine-treated male rats.

Sexual dysfunction is a common clinical condition due to different causes including the use of selective serotonin reuptake inhibitors (SSRI). Especially, SSRI paroxetine is known to cause numerous types of sexual dysfunction in men. There is growing interest in exercise as a non-pharmacological approach for the treatment of SSRI-induced sexual dysfunction. With these in mind, we investigated the effects of irisin, which is a recently detected exercise-linked hormone, on paroxetine-induced sexual dysfunction in male rats. Our findings showed that circulating irisin levels were lower in paroxetine-induced sexual dysfunction in male rats (20 mg/kg/day for 8 weeks by oral gavage than in vehicle-treated rats). In addition, results from sexual behavioral tests revealed that subcutaneous irisin perfusion (100 ng/kg/day via mini-osmotic pumps for 28 days) ameliorated sexual motivation and copulatory performance in sexually impaired male rats treated with paroxetine. The significantly reduced serum testosterone levels and α1-adrenoceptors (ADRA1A) and tyrosine hydroxylase gene (TH) expression levels in the nucleus accumbens (NAc) in paroxetine-induced sexually dysfunctioning male rats were markedly increased following irisin exposure. Similarly, the expression levels of ADRA1A and TH in the medial preoptic area (mPOA) significantly increased in male rats co-administered with paroxetine and irisin compared to the vehicle-treated male rats. These results demonstrate that irisin may be a therapeutic modality that mimics/supports the beneficial effects of exercise for improving SSRI-associated sexual dysfunction in men through increase in serum testosterone levels and increased expression of α1-adrenoceptors and TH in the NAc and mPOA associated with sexual motivation and copulatory behaviors.

An Investigation of the Antiproliferative Effect of Rhododendron luteum Extract on Cervical Cancer (HeLa) Cells via Nrf2 Signaling Pathway.

The aim of the present study was to investigate the role of Rhododendron luteum extract (RLE) in the induction of Nrf2­related oxidative stress and endoplasmic reticulum (ER) stress in human cervical cancer (HeLa) cells. The antiproliferative effect of RLE on HeLa and fibroblast cells was determined using the MTT assay. The effects of RLE on the cell cycle, apoptosis, and production of reactive oxygen species (ROS) in HeLa cells were evaluated using fluorescent probes. The mRNA expression levels of Nrf2 [and its targets glutamate-cysteine ligase catalytic subunit (GCLC), and glucose-6-phosphate dehydrogenase (G6PD)], and C/EBP homologous protein (CHOP, an ER stress marker were determined using reverse transcription­quantitative polymerase chain reaction (RT-PCR). The results demonstrated that RLE exhibited a selective cytotoxic effect (2.9-fold) on HeLa cells compared to fibroblast cells. RLE arrested the cell cycle at the S phase, and induced apoptosis, ER stress, and ROS formation. In addition, RLE significantly suppressed the expression levels of Nrf2, GCLC and G6PD (0.65, 0.69, and 0.54-fold, respectively) and increased the expression of CHOP (4.48-fold) in HeLa cells at 72 h of treatment (p < 0.05). These results show that the antiproliferative effect of RLE occurs through the Nrf2 and ER stress pathways, and the results should now be supported by further in vivo studies.

Functional and biochemical improvement following total knee arthroplasty in early postoperative period

SUMMARY OBJECTIVE: There are very few studies about total knee arthroplasty biomechanical and biochemical effects in the early postoperative period. The aim of this study was to investigate the effect of total knee arthroplasty on pain intensity, knee joint valgus angle, malalignment, functional status, knee joint position sense, and cytokine levels. METHODS: A total of 29 patients (female/male: 24/5) who underwent total knee arthroplasty were included in the late-stage knee osteoarthritis group, and 22 patients (female/male: 13/9) with grade 4 osteoarthritis were included in the early-stage knee osteoarthritis group. The visual analog scale and the Western Ontario and McMaster Universities Osteoarthritis Index were used to evaluate the pain intensity and functional status. Alignment and knee position sense measurements were also calculated. Systemic venous blood samples were taken to evaluate the interleukin-6, tumor necrosis factor-alpha, and interleukin-1 beta cytokine levels. RESULTS: In the study group, there were positive improvements in pain intensity, functional status, valgus angle, malalignment, amount of joint position sense deviation at 70° knee flexion angle parameters, and interleukin-6 of patients at the postoperative 6th week compared to the preoperative period (p<0.05). The patients in the study group had similar or better results in pain intensity, functional status, valgus angle, malalignment, amount of joint position sense deviation at 35°, 55°, and 70° knee flexion angles parameters, and in interleukin-6, compared to the control group at postoperative 6th week. CONCLUSION: Total knee arthroplasty provides improvements in pain, function, valgus angle, joint position sense, and interleukin-6 in the early postoperative period.

Effects of different lipid emulsions on serum adipokines, inflammatory markers and mortality in critically ill patients with sepsis: A prospective observational cohort study.

BACKGROUND & AIMS: Intravenous lipid emulsions in parenteral nutrition may cause different metabolic responses and immune effects in critically ill patients with sepsis. The aim of this study is to investigate the effects of different lipid emulsions on changes in concentrations of adipokine and cytokine and their relationship with mortality in patients. METHODS: Patients enrolled in this prospective, single-center, observational cohort study, were estimated to require more than ten days of parenteral nutrition. They were treated with soybean oil-based or olive oil-based parenteral lipid emulsions. Adipokine and cytokine concentrations of septic patients were determined at enrollment and ten days after, in accordance with the diagnostic criteria of SEPSIS-3. The concentrations levels were measured in an enzyme-linked immunosorbent assay. Mortality was analyzed using the Kaplan-Meier method and Cox regressions. RESULTS: Over a 25-month period, 145 patients were assessed for eligibility and consequently, 40 patients were analyzed. On admission, both groups had comparable physiological scores, comorbidities, malnutrition risk, anthropometric measurements, metabolic/hematologic biomarkers and concentrations of adipokines and cytokines (p > .05). Serum leptin, resistin, and cytokines (IL-6, IL-10, IL-1ß and TNF-α) decreased significantly in the entire cohort over ten days following sepsis (p < .05). Serum resistin decreased in both olive oil-based and soybean oil-based lipid emulsions groups. Serum adiponectin only decreased in soybean oil-based lipid emulsions group (p < .05). There was association between survival and percentage changes in adiponectin, resistin and visfatin concentrations (log rank test: p < .05). CONCLUSION: Adipokine and cytokine responses are affected by medical nutritional therapy in the sepsis process and adipokines may represent functional prognostic biomarkers in critically ill patients with sepsis.

Oxidative Stress and Serum S100B Levels in Adolescents with First-Episode Drug-Naive Unipolar Depression.

BACKGROUND: Unipolar depression is common among adolescents and has high recurrence rates. Studies conducted with adults show that oxidative stress plays a role in etiology of depression but studies with adolescent patients are limited. In addition, baseline S100B level in adult patients with depression is considered as a marker of response to treatment. The purpose of this study was to measure the levels of serum S100B, Malondialdehyde (MDA), total oxidant status (TOS), and total antioxidant status (TAS), which have not been previously investigated in adolescent patients with first-episode, drug-naive unipolar depression, and to investigate the relationship of these parameters with disease severity and patient-specific variables. SUBJECTS AND METHODS: This study was conducted with 37 adolescents diagnosed with unipolar depression and 37 healthy peers. Participants were asked to fill out the Beck Depression Scale, Screen for Child Anxiety Related Disorders, and suicide probability questionnaires. After this procedure, 5 cc blood was collected from the adolescents and serum S100B, MDA, TOS, and OSI levels measured. RESULTS: Serum S100B, MDA, TOS, and OSI levels were higher and TAS level was lower in patients than their healthy peers. There was no relationship between the patients' severity of depression or suicide probability and these parameters. The serum S100B, MDA, TOS, and OSI levels of female patients were higher than their healthy peers, but the TAS level was not different. Male patients had higher TOS and OSI levels and lower TAS levels than their healthy peers. CONCLUSIONS: The results show that increased serum S100B, MDA, TOS and OSI levels may contribute to etiology of depression regardless of gender. The gender-specific increase in S100B and MDA levels, which were significantly increased in female adolescent patients but not in males, should be supported by further follow-up studies.

The effect of homocysteine on the expression of CD36, PPARγ, and C/EBPα in adipose tissue of normal and obese mice.

The purpose of this study was to investigate the effect of homocysteine (Hcy) on CD36, PPARγ, and C/EBPα gene and protein expression in adipose tissue obtained from normal and high-calorie diet obesity models. CD36, PPARγ, and C/EBPα gene expression and protein levels in adipose tissue specimens were determined using the RT-PCR and ELISA methods, respectively. Significantly increased CD36 gene expression was observed in adipose tissue from obese mice, while Hcy significantly reduced CD36 gene expression in adipose tissue from normal and obese mice. PPARγ and C/EBPα gene expression levels decreased significantly in all groups compared to the normal group. In addition, levels of both PPARγ and C/EBPα gene expression were lower with Hcy supplementation compared to their own controls. In conclusion, Hcy's reduction of CD36 gene expression in adipose tissue may be one probable factor in hyperhomocysteinemia representing an independent risk factor for cardiovascular diseases.

Evaluation of circulating miR-122, miR-30c and miR-33a levels and their association with lipids, lipoproteins in postprandial lipemia.

AIMS: Postprandial lipemia is characterized by an increase in triglyceride-rich lipoproteins after fatty meals. MicroRNAs (miRs) play important roles in lipid and lipoprotein metabolism. The aim of this study was to determine relationship between levels of plasma miR expression and lipoprotein metabolism-related proteins in subjects with normal (NPR) and high postprandial response (HPR) in postprandial period. MATERIALS AND METHODS: The oral fat tolerance test was applied to 22 individuals with NPR and 22 with HPR. KEY FINDINGS: Increased expressions of miR-122 and miR-33a and miR-122/30c ratio and decreased miR-30c expression were observed in fasting and postprandial period of HPR compared with NPR. ROC curve analysis showed that miR-122/30c ratio is a good biomarker for postprandial lipemia (AUC: 0.97, p < 0.001). Levels of TG, MTTP, and Apo B-48 and chylomicron (CM) particle size were significantly higher in HPR than in NPR (p < 0.05). The miR-122/30c ratio at 2 h was positively correlated with CM particle size, and with TG, MTTP and Apo B-48 levels at 4th hour. miR-33a expression decreased in HPR and was negatively correlated with ABCA1 and Apo A-1 levels at 4th hour of the postprandial period in both groups. SIGNIFICANCE: Increased miR-122 and decreased miR-30c expression levels in HPR may play critical roles in elevated or prolonged postprandial lipemia. The miR122/30c ratio exhibited good association with MTTP, Apo B-48 and TG levels, and with CM particle size, and may be a reliable marker for evaluating postprandial lipemia. miR-33a may also play a key role in decreased HDL-C in postprandial lipemia.

Serum nesfatin-1, ghrelin, and lipid levels in adolescents with first episode drug naïve unipolar depression.

Background: Major depressive disorder (MDD) is a mental health and emotional disorder that affects children and adolescents worldwide. This study aimed to evaluate serum nesfatin-1, ghrelin, and lipid levels as biological markers of adolescent MDD and their relationship with the severity of depression-anxiety and suicide risk in MDD. Methods:This study included 37 drug naïve adolescents between the ages of 12 and 18 who were diagnosed with a first episode MDD according to the Kiddie Schedule for Affective Disorders and Schizophrenia for School-Age Children-Present and Lifetime Version (K-SADS-PL) and DSM-V diagnostic criteria. Thirty-three healthy adolescents between the ages of 12 and 18 were included as the control group. The Children's Depression Inventory (CDI), Screen for Child Anxiety Related Disorders (SCARED), and Suicide Probability Scale (SPS) were used to evaluate the subjects in the MDD and control groups. In the first stage, serum nesfatin-1, ghrelin, and lipid levels were compared between the adolescents diagnosed with MDD and the control group. Next, the correlations between these levels and the CDI, SCARED, and SPS scores were evaluated. Results: Nesfatin-1 levels were significantly lower in the MDD group than the control group (p < 0.001) A positive correlation was found between the nesfatin-1 levels and the SPS scores. Conclusions: This is the first study to evaluate nesfatin-1 levels in adolescent depression, suggesting that nesfatin-1, ghrelin, total cholesterol, and low-density lipoprotein cholesterol (LDL) levels can be used as biomarkers in child-adolescent MDD. However, it is evident that further studies with larger samples and post-treatment measurements are needed.

HMGB-1, TLR4, IL-1R1, TNF-α, and IL-1ß: novel epilepsy markers?

The purpose of this study was to compare HMGB-1, TLR4, IL-1ß, IL-1R1, and TNF-α levels in patients with mild and severe epilepsy with those in a healthy control group. Children aged 4-17 years, diagnosed with epilepsy for at least three years and with no progressive neurological disease, metabolic disease or infection, were selected for the study. The severe epilepsy group consisted of 28 children with at least one episode a week despite receiving three or more antiepileptic drugs. The mild epilepsy group consisted of 29 children with no seizures in the previous year, receiving only one antiepileptic drug, while 27 healthy children were selected as the control group. HMGB-1, TLR4, IL-1R1, TNF-α and IL-1ß levels were investigated in these three groups. The MRI findings and clinical characteristics of the patients in the epilepsy group were also compared with these markers. HMGB-1, TLR4, TNF-α, and IL-1ß levels in the severe epilepsy group were higher than in the control group and the mild epilepsy group (p<0.05), and were higher in the mild epilepsy group than in the control group (p<0.05). IL-1R1 was also higher in the severe epilepsy group than in the control group (p<0.05). In this first report to identity a possible correlation between HMGB-1, TLR4, IL-1ß, IL-1R1, and TNF-α levels and severity of epilepsy, our data demonstrates that the serum level of these cytokines is higher in cases of drug-refractory epilepsy.

l-theanine alleviates liver and kidney dysfunction in septic rats induced by cecal ligation and puncture.

AIMS: Sepsis is defined as a life-threatening organ dysfunction caused by a dysregulated host response against infection that triggers systemic inflammatory response syndrome. l-theanine (LT), a glutamate derivative, is a non-protein amino acid derived from tea (Camellia sinensis), and a valuable nutraceutical product used as an additive in the food industry. This study we aimed to investigate whether LT would exert any therapeutic effect on liver and kidney tissues in Sprague Dawley rats with sepsis induced with cecal ligation and puncture (CLP). MAIN METHODS: Rats were divided into four groups; sham, CLP, CLP+LT1 (2x250 mg/kg) and CLP+LT2 (2 × 750 mg/kg). Liver and kidney tissues were subjected to histopathological examination. Apoptotic index percentages (AI%) were examined using the TUNEL method. The oxidized glutathione to total glutathione (GSSG/TGSH) ratio (as a marker of oxidative stress, levels of caspase-3 (a marker of apoptosis), glutathione peroxidase (GPx) and glutathione S-transferase (GST) (as antioxidant enzymes), inducible nitric oxide synthase (iNOS) and the tumor necrosis factor-α to Interleukin-10 ratio (TNF-α/IL-10) (as markers of inflammation) were investigated using commercial kits. Levels of malondialdehyde (MDA) (a marker of oxidative stress) were determined spectrophotometrically. KEY FINDINGS: A high dose of LT exhibited more significant effects in reducing oxidative stress, inflammation and apoptosis than a low dose of LT in liver and kidney tissues with CLP-induced sepsis (p < 0.05). SIGNIFICANCE: Our results indicated that LT significantly and dose-dependently inhibited sepsis induced liver and kidney injury. This effect may be attributed to the antioxidant, anti-inflammatory, and anti-apoptotic activities of LT.

Dorycnium pentaphyllum Extract Has Antiproliferative Effect on Human Cervix and Colon Cancer Cells.

Although several studies have investigated the cytotoxic effects of different Fabaceae species, limited researches have been conducted on the cytotoxic effect of Dorycnium pentaphyllum. The aim of this study was to evaluate the phenolic characterization and the cytotoxic effect of D. pentaphyllum on human cervix (HeLa) and colon (WiDr) cancer cells and the possible mechanisms involved. Total phenolic content (TPC) and phenolic characterization of the extract were investigated using the Folin-Cioceltau method and RP-HPLC, respectively. The cytotoxic effect of the extract was evaluated using the MTT assay. The mechanism involved in the extract's cytotoxic effect was then evaluated in terms of apoptosis and the cell cycle using flow cytometry, while mitochondrial membrane potential (MMP) was investigated using the fluorometric method. The TPC value of the extract was 141.2 ± 0.8 mg gallic acid equivalent per g sample, and quercetin was detected as major phenolics. D. pentaphyllum extract exhibited a selective cytotoxic effect on HeLa and WiDr cells compared to normal fibroblast and colon cells, respectively. The extract induced cell cycle arrest at the S phase and apoptosis via reduced MMP in these cells. Further studies may be useful in developing a natural product based new generation pharmacological agent.

Effect of ethyl pyruvate on oxidative state and endoplasmic reticulum stress in a rat model of testicular torsion.

We investigated the effects of ethyl pyruvate (EP) on oxidative and endoplasmic reticulum (ER) stress due to experimental testicular ischemia-reperfusion (I-R). Eighteen rats were divided into a control group, a torsion-detorsion (T-D) group and an EP group. For pretreatment of the EP group, 50 mg/kg EP was given intraperitoneally (i.p.) 30 min before detorsion. Tissue 4-hydroxynonenal (4-HNE) and 78-kDa glucose-regulated protein (GRP78) levels were determined using enzyme-linked immunosorbent assay (ELISA) kits. Tissue total oxidant status (TOS) and total antioxidant status were determined using colorimetric methods. Histology of the tissues was evaluated using hematoxylin and eosin staining. In the T-D group, tissue 4-HNE, GRP78, TOS and oxidative stress index levels were significantly higher than for the control group. The increases were reduced significantly by EP pretreatment. Our findings suggest that EP can inhibit I-R induced testicular injury by suppressing oxidative and ER stress. EP may be a useful adjunctive treatment for surgical repair in humans.

Hazelnut consumption improves testicular antioxidant function and semen quality in young and old male rats.

The effects of hazelnut supplemented diet on the reproductive system of young and old male rats were investigated. Young male rats were grouped into young control group (YCG) and young hazelnut group (YHG). Old male rats were grouped into old control group (OCG), old hazelnut group (OHG), and old vitamin E group (OEG). While YCG and OCG were given rat feed, YHG and OHG were given rat feed supplemented with hazelnut (3 g/kg body weight). OEG was subjected to rat feed and administered vitamin E (50 mg/kg body weight). When YCG and OCG were compared, aging increased histopathological damage and decreased sperm quality. Hazelnut supplemented diet improved histopathological variables, sperm quality, seminal plasma and plasma oxidative stress, seminal plasma vitamin E, and plasma testosterone levels in both groups. The present work suggests that hazelnut supplemented diet significantly improves testicular antioxidant function and semen quality in old male rats.

Neurocognitive Functions in Infants with Malnutrition; Relation with Long-chain Polyunsaturated Fatty Acids, Micronutrients Levels and Magnetic Resonance Spectroscopy.

PURPOSE: Malnutrition may influence neurocognitive development in children by directly affecting the brain structural development, or indirectly by affecting the children's cognition experience. Malnutrition alters the cell numbers, cell migration, synaptogenesis, and neurotransmission due to inadequate availability of necessary micronutrients to support cell growth. We aimed to analyze neurocognitive development in infants with malnutrition and its association with long chain polyunsaturated fatty acids (LC-PUFA), micronutrients levels and magnetic resonance spectroscopy (MRS) findings. METHODS: The study included two groups; group 1, infants with malnutrition (n=24), group 2; healthy infants (n=21). Peripheral blood was obtained from the participants for studying micronutrients and LC-PUFA levels. The neurocognitive development was analyzed by the use of an Ankara Developmental Screening Inventory test. MRS were performed on all infants. RESULTS: All parameters of neurocognitive development and serum calcium (9.6±0.9 mg/dL vs. 10.4±0.3 mg/dL, p<0.05) and magnesium (2.02±0.27 mg/dL vs. 2.2±0.14 mg/dL, p<0.05) levels were noted as being low in infants with marked malnutrition. No difference was found in LC-PUFA levels between healthy and malnourished infants. Thalamic choline/creatine levels were significantly high in infants with malnutrition (1.33±0.22 vs. 1.18±0.22, p<0.05). Total neurocognitive development in infants was positively correlated with serum calcium levels (p<0.05, r=0.381). CONCLUSION: Calcium supplementation may improve neurocognitive development in malnourished infants.

Serum carbonic anhydrase I and II autoantibodies in patients with chronic lymphocytic leukaemia.

Cancer is the second most important cause of mortality, and millions of people either have or have had the disease. Leukaemia is one of the most common forms of cancer. Autoantibodies that have developed against the organism's self-antigens are detected in the sera of subjects with cancer. In recent years carbonic anhydrase (CA) autoantibodies have been determined in some autoimmune diseases and carcinomas, but the mechanisms underlying this immune response have not yet been fully explained. The purpose of this study was to determine CA I and II autoantibodies in subjects with chronic lymphocytic leukaemia (CLL) and to provide a novel perspective regarding the autoimmune basis of the disease. Autoantibody levels were investigated using enzyme-linked immunosorbent assay (ELISA) in serum samples from 37 patients with CLL and 37 healthy peers. Anti-CA I titres in the CLL group were significantly higher compared with the control group (p = 0.0001). However, there was no significant difference between CLL and control groups in terms of anti-CA II titres (p = 0.278). The prevalences of CA I and II autoantibodies in patients with CLL in this study were 27% and 24.3%, respectively. Our results suggest that these autoantibodies may be involved in the pathogenesis of CLL. More extensive studies are now needed to reveal the entire mechanism.

Primula vulgaris extract induces cell cycle arrest and apoptosis in human cervix cancer cells.

Primula vulgaris belongs to the genus Primula, members of which are frequently used in folk medicine. Various studies have investigated the cytotoxic effect of different Primula species, but there have been limited studies on the cytotoxic effect of P. vulgaris. The aim of this study was to investigate the cytotoxic effects, and possible mechanisms involved, of P. vulgaris flower extract on human cervical cancer (HeLa) cells. The cytotoxic effect of the extract on HeLa cells was revealed using the MTT assay. Mechanisms involved in the extract's cytotoxic effect were then investigated in terms of apoptosis, mitochondrial membrane potential, and the cell cycle, using fluorometric methods. P. vulgaris flower extract exhibited selective cytotoxic effects against HeLa cells by arresting their cell cycle at the S phase, and inducing the number of apoptotic cells compared to normal fibroblast cells by reducing mitochondrial membrane potential in a concentration-dependent manner. This is the first study to reveal the antiproliferative effect of P. vulgaris flower extract. Further studies are now needed to identify the cytotoxic molecules in the extract and their mechanisms.

The clinical importance of serum galectin-3 levels in breast cancer patients with and without metastasis.

OBJECTIVE: Studies have investigated expression status of galectin-3 (Gal-3), but very little is known about the importance of circulating Gal-3 in patients with breast cancer (BC). The purpose of the study was to investigate the clinical significance and potential diagnostic value of plasma Gal-3 levels in patients with BC. MATERIALS AND METHODS: Fifty-two patients with BC and 35 age-matched healthy controls were enrolled. Levels of Gal-3 were investigated in BC patients and healthy controls. Gal-3 levels were determined using ELISA method. RESULTS: Serum Gal-3 levels were significantly higher in BC patients than in controls (P = 0.002). Gal-3 levels did not significantly differ according to patients' statuses of lymph node involvement, hormone receptor, lymphovascular invasion, e-cadherin, menopausal, stage, serum hemostatic markers (prothrombin time, partial thromboplastin time, and international normalized ratio), platelet counts, mean platelet volume, lactate dehydrogenase, carcinoembryonic antigen, and carbohydrate antigen 15-3 values (P > 0.05 for all). A cut-off value of Gal-3 to predict BC was determined at ≥3.17 ng/ml with a sensitivity of 75.0%, a specificity of 65.71%, a positive and negative predictive values of 76.5 and 63.9%, respectively (area under the curve: 0.705 [95% confidence interval, 0.598-0.798], P = 0.0002). CONCLUSION: Serum Gal-3 levels were significantly higher in BC patients and did not significantly differ according to clinical and tumoral characteristics of patients. Furthermore, there was no difference in Gal-3 levels between BC patients with and without metastatic disease. Serum Gal-3 levels can be used as an adjunct to other diagnostic or screening tests for BC regardless of clinical and tumoral characteristics of patients.