Evaluation of soluble lectin-like oxidized low-density lipoprotein receptor-1 (sLOX-1) and sLOX-1/oxidized LDL ratio as novel biomarkers of acute coronary syndrome.

The lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in the pathophysiology of atherosclerosis and acute coronary syndromes (ACS). In patients with acute coronary syndrome, circulating soluble LOX-1 (sLOX-1) levels are dramatically elevated. This study aimed to assess sLOX-1 levels in acute coronary syndromes and determine the ratio of sLOX-1 and oxidative LDL in cases of myocardial infarction and unstable angina pectoris and the ROC curve for this ratio sLOX-1. A case-control study was conducted at the department of chemistry and biochemistry, college of medicine, Al- Nahrain University, Baghdad, Iraq, from September 2020 to January 2021. In a total of 90 subjects (30 patients with myocardial infarction within the first six hours of chest pains, 30 patients with unstable angina pectoris, and 30 healthy donors). The ELISA technique measured concentrations of sLOX-1 and oxidized LDL. In addition, Troponin and highly sensitive C reactive protein were measured by the same technique (Fluorescence immune assay), and lipid profile was measured using the Spectrophotometer technique. The median level of sLOX-1 in MI group was 476.17 pg/ml (90.88-675.4 pg/ml) which was significantly higher than that of UA patients (median=289.1 pg/ml [62.74-585.43 pg/ml]) and controls (median=144.52 pg/ml [79.17-283.83 pg/ml]) with highly significant differences and the median sLOX-1/OX-LDL ratio in patients with MI was 64.6 (range 15.17-100.15) which was significantly higher than either patients with UA (median=37.6 [7.06-88.65]) or controls (median=25.29 [12.7-43.04]). There were elevated levels of sLOX-1 in acute coronary syndromes. The sLOX-1/oxidized LDL ratio also strongly indicated the diagnosis and a discriminatory force on the ROC curve for myocardial infarction.

CAR-NK cell in cancer immunotherapy; A promising frontier.

Chimeric antigen receptors (CARs) have a unique facet of synthetic biology and offer a paradigm shift in personalized medicine as they can use and redirect the patient's immune cells to attack cancer cells. CAR-natural killer (NK) cells combine the targeted specificity of antigens with the subsequent intracellular signaling ability of the receptors to increase their anti-cancer functions. Importantly, CAR-NK cells can be utilized as universal cell-based therapy without requiring human leukocyte antigen (HLA) matching or earlier contact with tumor-associated antigens (TAAs). Indeed, CAR-NK cells can be adapted to recognize various antigens, hold higher proliferation capacity, and in vivo persistence, show improved infiltration into the tumors, and the ability to overcome the resistant tumor microenvironment leading to sustained cytotoxicity against tumors. Accumulating evidence from recent in vivo studies rendering CAR-NK cell anti-cancer competencies renewed the attention in the context of cancer immunotherapy, as these redirected effector cells can be used in the development of the "off-the-shelf" anti-cancer immunotherapeutic products. In the current review, we focus on the therapeutic efficacy of CAR-NK cell therapies for treating various human malignancies, including hematological malignancies and solid tumors, and will discuss the recent findings in this regard, with a special focus on animal studies.

The diagnostic power of circulating micro ribonucleic acid 34a in combination with cancer antigen 15-3 as a potential biomarker of breast cancer.

OBJECTIVES: To investigate the circulating levels of microRNA-34a (miRNA-34a) as a novel non-invasive biomarker of breast cancer (BC). Methods: The case-control study was conducted at the Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq, from December 2018 to April 2019. Real-time quantitative polymerase chain reaction has been employed to analyze miRNA-34a expression in the samples of serum from 90 participants (30 patients with BC 30 patients with benign breast tumors and 30 control subjects) after RNA extraction and reverse transcription. Cancer antigen 15-3 (CA15-3) and carcinoembryonic antigen (CEA) were measured by ELISA. Additionally, we analyzed the receiver operating characteristic curves of various markers, including miRNA -34a, CA15-3, and CEA, to assess the diagnostic power of each marker.  Results: The expression of miRNA-34a has been significantly lower in the group of breast cancer compared with that in the group of control, and miRNA-34a expression has been significantly reduced in the group of benign breast tumor compared as that in the group of control. Receiver operating characteristics analysis showed a very good discriminative power of combined miRNA-34a and CA15-3 (specificity=77.7%; sensitivity=83.3% and areas under the curve =0.842) for BC patients. Conclusion: MicroRNA-34a expression is significantly decreased in the patients' serum with the cancer of breast, and miRNA-34a can be employed as a potential non-invasive molecular marker for the early diagnosis of BC.

Clinical value of peripheral blood M2/M1 like monocyte ratio in the diagnosis of breast cancer and the differentiation between benign and malignant breast tumors.

BACKGROUND: During tumor progression, circulating monocytes and macrophages are actively recruited into tumors where they alter the tumor microenvironment to accelerate tumor progression. In response to multiple microenvironmental signals from the tumor and stromal cells, macrophages change their functional phenotypes. Based on their function, macrophages are commonly classified into both, classical M1 and alternative M2 macrophages. M2-like tumor-associated macrophages promote breast tumor growth and survival, and may migrate into the peripheral blood. However, the level of circulating M2/M1-like monocyte ratio in the peripheral blood of breast cancer patients has not been yet clarified. AIM: To compare peripheral blood M2/M1 monocyte ratio among breast cancer patients, benign breast tumor patients and healthy subjects. Also, to investigate the role of peripheral blood M2/M1 monocyte ratio as a circulating breast cancer tumor marker and to asses the validity of this marker in differentiation between benign and malignant breast tumors. METHODS: Flow cytometry technique was used to determine the peripheral blood M2/M1 monocyte ratio in three groups of subjects, i.e. 45 patients with breast cancer, 40 patients with benign breast tumor, and 40 healthy subjects as a control group. The results of carbohydrate antigen15-3 (CA15-3) determination were analyzed comparatively. RESULTS: The peripheral blood M2/M1 monocyte ratio in patients with breast cancer (0.27±0.1) was significantly higher (P<0.001) than that in healthy subjects (0.07±0.05) and than in benign tumor subjects (0.08±0.04). The area under the receiver operating characteristic (ROC) curve of peripheral blood M2/M1 monocyte ratio determination was significantly higher (P≤0.001) than that of CA15-3 levels. CONCLUSION: M2/M1-like monocyte ratio is of a high diagnostic value for breast cancer and is a promising differentiating marker between benign and breast cancer tumor groups.

Serotonin and serotonin transporter levels in autistic children.

OBJECTIVES: To assess the possible correlation between serotonin and serotonin transporter (SERT) with the autism severity and investigate the association between these parameters in autistic children to assess their possible role for diagnosis of autism severity. METHODS: A comparative cross-sectional study was carried out in the Chemistry and Biochemistry Department, College of Medicine, Al-Nahrain University, Baghdad, Iraq while the samples were taken from 60 male autistic children recruited to the Department of Pediatrics at Al-Sader Hospital, Baghdad, Iraq between November 2014 amd April 2015. Levels of serotonin and serotonin transporters (SERT) were determined in 60 male autistic Iraqi patients classified into mild, moderate and severe (20 for each). These levels were compared with those of 26 healthy control children. Results: Levels of serotonin and SERT were significantly increased in autistic children than that of gender and age-matched controls. Serotonin levels were 80.63± 21.83 ng/ml in mild, 100.39±23.07 ng/ml moderate, and 188.7±31.72 ng/ml severe autistic patients. Serotonin transporter levels were 10.13±4.51 ng/ml in mild, 13.15±4.71 ng/ml moderate, and 16.32±6.7 ng/ml in  severe autistic patients. The increase of both serotonin and SERT levels were associated with severity of autism. Receiver operating characteristic (ROC) analysis  can be used for diagnostic and prognostic purposes. CONCLUSIONS: High serotonin and SERT levels may indicate that these biomarkers have a role in the autism pathogenesis and support the possibility of using serotonin and SERT to diagnose autism severity.

Low oxytocin and melatonin levels and their possible role in the diagnosis and prognosis in Iraqi autistic children.

UNLABELLED:   OBJECTIVES: To test the possible association between oxytocin and melatonin levels with the severity of social and cognitive dysfunctions, and to study the correlation between these parameters in children with autism. METHODS: A case-control study was carried out in the Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq. The study was performed on 60 male autistic patients recruited from the Pediatric Department of Al-Sader General Hospital, Baghdad, Iraq between November 2014 and April 2015. The levels of oxytocin and melatonin were measured in the serum of these autistic male patients, and categorized as mild, moderate, and severe (20 patients each), and was compared with 26 age- and gender-matched control subjects. RESULTS: The data indicated that the levels of oxytocin (44.72 ± 36.1 µIU/mL) and melatonin in patients (23.08 ± 10.41 pg/mL) were significantly lower (p less than 0.05) than that of age-matched (102.1 ± 34.31 µIU/mL) and gender-matched controls (53.05 ± 38.38 pg/mL). These parameters were remarkably associated with the severity of the disease that was indicated by the significant decrease in the levels of oxytocin (47 ± 25.47 µIU/mL) and melatonin in moderate (20 ± 6.14 pg/mL), and patients with severe oxytocin (27.92 ± 10.23 µIU/mL) and patients with severe melatonin (21.69 ± 7.02 pg/mL) when compared with mild autistic patients with oxytocin (59.22 ± 27.32 µIU/mL) and melatonin (27.55 ± 14.71 pg/mL). These 2 parameters showed a significant positive correlation with each other in moderate (r=0.513; p=0.021), and severe patients (r=0.598; p=0.005).  CONCLUSION: Receiver operating characteristic analysis revealed that oxytocin can be considered as a good diagnostic marker in severe autistic patients while melatonin can be considered as a good diagnostic marker in all autistic subgroups. This study proves the possibility of using oxytocin and melatonin in the diagnosis, and as markers of autism severity.

The Values of CA-125, Progesterone, ß-HCG and Estradiol in the Early Prediction of Ectopic Pregnancy.

OBJECTIVE: To explore the diagnostic value and measurement of serum CA-125, the single measurement of progesterone (P), ß-HCG, and estradiol (E2) in the early diagnosis of ectopic pregnancy. METHODS: Serum levels of CA-125, progesterone, ß-HCG and estradiol were measured by Enzyme Linked Immuno Sorbent Assay (ELISA) techniques in 40 symptomatic women with ectopic pregnancy and 24 women with normal intrauterine pregnancy during gestational age of 4-10 weeks at Al-Kadhmiya Teaching Hospital, Baghdad, Iraq, between November 2010 and June 2011. RESULTS: The mean ±SEM serum levels of CA-125, progesterone, ß-HCG, and estradiol in patients with ectopic pregnancies (16.51±2.39U/ml; 2.54±0.47ng/ml; 72.75±12.27mIU/ml; 13.4±2.14pg/ml; respectively) were significantly lower than the levels in normal intrauterine pregnancies (74.25±18.5U/ml; 28.36±3.7ng/ml; 249.54±18.0mIU/ml; 112.7±23.6pg/ml; respectively). When using a CA-125 concentration of 20.5 U/ml as a cut-off value for the diagnosis of ectopic pregnancy, sensitivity was 75.7%, specificity 100%, the positive predictive value was 100% and the negative predictive value 71.4%. CONCLUSION: The measurement of CA-125 and progesterone levels is useful in discriminating ectopic from normal gestations.

Coenzyme Q10 and oxidative stress markers in seminal plasma of Iraqi patients with male infertility.

OBJECTIVE: To evaluate seminal plasma coenzyme Q10 (CoQ10) levels and oxidative stress in patients with different types of male infertility. METHODS: A case-control study was carried out in the Department of Chemistry and Biochemistry, College of Medicine, Al-Nahrain University, Baghdad, Iraq from the period of November 2004 to July 2006. Sixty patients with male infertility were recruited from Al-Kadhimia Teaching Hospital, Baghdad and included in this study. The male patients were categorized according to their seminal fluid parameters to oligozoospermia (n=32), azoospermia (n=22), and asthenozoospermia (n=6). All obtained results from infertile men groups were compared with age-matched healthy volunteers as control group consisting of 39 subjects. Seminal plasma samples were analyzed for CoQ10 by an improved high performance liquid chromatography (HPLC) method and for malondialdehyde (MDA) as an index of oxidative stress. RESULTS: The mean seminal plasma CoQ10 was 1.10+/-0.169 mg/L in oligozoospermia, 0.567+/-0.098 mg/L in azoospermia, 0.740+/-0.06 mg/L in patients with asthenozoospermia, and 1.652+/-0.139 mg/L in control group. The seminal plasma CoQ10 levels in all infertility groups showed a significant difference from the control group (p< or =0.0001). High significant increase (p < or =0.001) in the MDA levels was noted in the seminal plasma of oligozoospermia 11.37+/-1.64 micromole/L, azoospermia 13.87+/-1.62 micromole/L, and asthenozoospermia group 9.508+/-0.533 micromole/L whereas the level in the control group was 8.517+/- 0.622 mole/L. Seminal plasma CoQ10 was inversely and significantly correlated with MDA (r= -0.760; p=0.000). CONCLUSION: Elevated seminal plasma CoQ10 levels are associated directly with good semen parameters and inversely with the oxidative stress.

Association between seminal plasma copper and magnesium levels with oxidative stress in iraqi infertile men.

OBJECTIVES: To study the association between copper, magnesium and malondialdehyde levels in seminal plasma of oligozoospermic, azoospermic in relation to normozoospermic men. METHODS: The present study was conducted at the Chemistry and Biochemistry department, College of Medicine, Al-Nahrain University, Baghdad-Iraq during September 2007 to February 2008 after obtaining approval from the research and ethics committee and obtaining written consent, 78 infertile men (age range 33.01±4.20 years) were recruited at the institute of embryo research and infertility treatment, Al-Kadhimiya teaching hospital, Iraq and were categorized according to their seminal fluid parameters to oligozoospermia (n=43) and azoospermia (n=35). 41 fertile men (age range 30.29±2.30 years) were selected as controls. Seminal plasma copper and magnesium were measured by atomic absorption spectrophotometry. Malondialdehyde was measured calorimetrically using thiobarbituric acid assay which detects thiobarbituric acid reactive substances. RESULTS: Seminal plasma copper level was decreased significantly (p=0.000) in the azoospermic group compared to the control group. Whereas, the level decreased non-significantly in the oligozoospermic group. Seminal plasma magnesium levels were decreased significantly (p=0.000) in all the infertility groups studied. On the other hand, malondialdehyde levels which is an end product of lipid peroxidation were significantly elevated (p=0.000) in all the infertility groups studied. CONCLUSION: Copper and magnesium work in different ways in order to maintain normal environment for spermatozoa for normal fertilization to occur.

Serum γ-glutamyltransferase as Oxidative Stress Marker in Pre-and Postmenopausal Iraqi Women.

OBJECTIVES: The primary role of γ-glutamyltransferase is to metabolize reduced glutathione by assimilating and utilizing precursor amino acids for intracellular glutathione synthesis. The aim of this study is to investigate the exact role of γ- glutamyltransferase enzyme in the oxidative stress associated with menopause. METHODS: This study was carried out at the Chemistry and Biochemistry department, Al-Nahrain University from October 2009 to January 2010. The study participants were categorized into two groups; premenopausal group (n=17) and postmenopausal group (n=16). Blood specimens were collected from each participant by vein puncture procedure. The γ-glutamyltransferase enzyme was measured by kinetic spectrophotometric method while glutathione and malondialdehyde were measured by spectrophotometric methods. RESULTS: Serum glutathione levels in pre- and postmenopausal women were 0.62±0.17 and 0.47±0.11 mmol/L respectively. Serum γ-glutamyltransferase levels increased significantly in the postmenopausal women group (p=0.025) compared to the premenopausal women group. Serum malondialdehyde levels were 1.04±0.06 and 1.32±0.05 µmol/L in pre- and postmenopausal groups respectively. CONCLUSION: Serum γ-glutamyltransferase may be considered as an index of oxidative stress associated with menopause.

Development of a new high performance liquid chromatography method for measurement of coenzyme Q10 in healthy blood plasma.

OBJECTIVE: To improve a new high performance liquid chromatography (HPLC) method for coenzyme Q10 (CoQ10) measurement in human plasma. METHODS: We conducted this study in the Chemistry and Biochemistry Department, College of Medicine, Al-Nahrain University, Baghdad, Iraq from September 2004 to July 2005. Sixty healthy volunteers aged 28.51+/-7.30 years were participated in this study. All participants were non-smokers and under no any treatment for the last 3 days and fast for 12 hours before analysis. Coenzyme Q10 levels were measured by improved isocratic reversed phase HPLC technique after one-step ice-cold 1-propanol extraction step. RESULTS: The ultra violet (UV) detection, developed HPLC method gives a good linearity range between 0.1-4.0 mg/L. The coefficients of variations (CVs%) of within-day precision for CoQ10 in human plasma were 0.2-3.90%. Analytical recoveries were 95.5-101.30%, whereas the average CV% of CoQ10 reproducibility was 0.959%. CONCLUSION: A new improved rapid, precise, and sensitive HPLC method for the quantitation of CoQ10 is suitable for analysis of blood plasma samples.

The relationship between seminal plasma zinc levels and high molecular weight zinc binding protein and sperm motility in Iraqi infertile men.

OBJECTIVE: To evaluate the relationship between sperm motility and total seminal plasma zinc concentration and high molecular weight zinc bound protein values in infertile Iraqi men. METHODS: A case-control study was conducted at the Chemistry and Biochemistry Department, College of Medicine, Al-Nahrain University, Baghdad, Iraq between March 2005 to February 2006. The subjects for the study included 60 infertile male patients who were recruited Al-Kadhimiya Teaching Hospital, and Institute of Embryo Research and Infertility Treatment, Baghdad, Iraq. They were categorized according to their seminal parameters to oligozoospermia (n=32), azoospermia (n=22), and asthenozoospermia (n=6). Thirty nine fertile men (age range 31.87 +/- 3.76 years) were selected as controls, whose partners had conceived within the last year before participation with this study, and having normal spermiogram parameters. Seminal plasma zinc concentration and high molecular weight zinc binding proteins (HMW-Zn) were assayed in the ejaculates of fertile and infertile men. RESULTS: The seminal plasma zinc levels were 181.92 +/- 23.40 ug/mL in the oligozoospermia group, 178.50 +/- 18.61 ug/mL in the azoospermia group, 195.33 +/- 13.00 ug/mL in the asthenozoospermia group, and 184.66 +/- 21.31 ug/mL in the control group. CONCLUSION: The HMW-Zn% is a good index of sperm function rather than the total seminal plasma zinc levels.