Search results for: hereditary breast-ovarian cancer syndrome

Authors: Shouta Sora, Shizuki Kuriu, Radhika Mishra, Ariunbuyan Sukhbaatar, Maya Sakamoto, Shiro Mori, Tetsuya Kodama

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Lymph node (LN) metastasis accounts for 20 - 30 % of all deaths in patients with head and neck cancer. Therefore, the control of metastatic lymph nodes (MLNs) is necessary to improve the life prognosis of patients with cancer. In a classical metastatic theory, tumor cells are thought to metastasize hematogenously through a bead-like network of lymph nodes. Recently, a lymph node-mediated hematogenous metastasis theory has been proposed, in which sentinel LNs are regarded as a source of distant metastasis. Therefore, the treatment of MLNs at the early stage is essential to prevent distant metastasis. Radiation therapy is one of the primary therapeutic modalities in cancer treatment. In addition, total body irradiation (TBI) has been reported to act as activation of natural killer cells and increase of infiltration of CD4+ T-cells to tumor tissues. However, the treatment effect of TBI for MLNs remains unclear. This study evaluated the possibilities of low-dose total body irradiation (L-TBI) and middle-dose total body irradiation (M-TBI) for the treatment of MLNs. Mouse breast cancer FM3A-Luc cells were injected into subiliac lymph node (SiLN) of MXH10/Mo/LPR mice to induce the metastasis to the proper axillary lymph node (PALN) and lung. Mice were irradiated for the whole body on 4 days after tumor injection. The L-TBI and M-TBI were defined as irradiations to the whole body at 0.2 Gy and 1.0 Gy, respectively. Tumor growth was evaluated by in vivo bioluminescence imaging system. In the non-irradiated group, tumor activities on SiLN and PALN significantly increased over time, and the metastasis to the lung from LNs was confirmed 28 days after tumor injection. The L-TBI led to a tumor growth delay in PALN but did not control tumor growth in SiLN and metastasis to the lung. In contrast, it was found that the M-TBI significantly delayed the tumor growth of both SiLN and PALN and controlled the distant metastasis to the lung compared with non-irradiated and L-TBI groups. These results suggest that the M-TBI is an effective treatment method for MLNs in the early stage and distant metastasis from lymph nodes via blood vessels connected with LNs.

Keywords: metastatic lymph node, lung metastasis, radiation therapy, total body irradiation, lymphatic system

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Authors: Jer-Yuh Liu, Je-Chiuan Ye, Jin-Ming Hwang

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Protein kinase C alpha (PKCα) is a key signaling molecule in human cancer development. As a therapeutic strategy, targeting PKCα is difficult because the molecule is ubiquitously expressed in non-malignant cells. PKCα is regulated by the cooperative interaction of the transcription factors myeloid zinc finger 1 (MZF-1) and Ets-like protein-1 (Elk-1) in human cancer cells. By conducting tissue array analysis, herein, we determined the protein expression of MZF-1/Elk-1/PKCα in various cancers. The data show that the expression of MZF-1/Elk-1 is correlated with that of PKCα in hepatocellular carcinoma (HCC), but not in bladder and lung cancers. In addition, the PKCα down-regulation by shRNA Elk-1 was only observed in the HCC SK-Hep-1 cells. Blocking the interaction between MZF-1 and Elk-1 through the transfection of their binding domain MZF-160–72 decreased PKCα expression. This step ultimately depressed the epithelial-mesenchymal transition potential of the HCC cells. These findings could be used to develop an alternative therapeutic strategy for patients with the PKCα-derived HCC.

Keywords: protein kinase C alpha, myeloid zinc finger 1, ets-like protein-1, hepatocellular carcinoma

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Authors: Krima M. Rohela, Raja Sabarinath Sundaralingam

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Humans have been launching rockets since the beginning of the space age in the late 1950s. We have come a long way since then, and the success rate for the launch of rockets has increased considerably. With every successful launch, there is a large amount of junk or debris which is released into the upper layers of the atmosphere. Space debris has been a huge concern for a very long time now. This includes the rocket shells released from the launch and the parts of defunct satellites. Some of this junk will come to fall towards the Earth and burn in the atmosphere. But most of the junk goes into orbit around the Earth, and they remain in orbits for at least 100 years. This can cause a lot of problems to other functioning satellites and may affect the future manned missions to space. The main concern of the space-debris is the increase in space activities, which leads to risks of collisions if not taken care of soon. These collisions may result in what is known as Kessler Syndrome. This debris can be removed by a space-based laser targeting system. Hence, the matter is investigated and discussed. The first step in this involves launching a satellite with a high-power laser device into space, above the debris belt. Then the target material is ablated with a focussed laser beam. This step of the process is highly dependent on the attitude and orientation of the debris with respect to the Earth and the device. The laser beam will cause a jet of vapour and plasma to be expelled from the material. Hence, the force is applied in the opposite direction, and in accordance with Newton’s third law of motion, this will cause the material to move towards the Earth and get pulled down due to gravity, where it will get disintegrated in the upper layers of the atmosphere. The larger pieces of the debris can be directed towards the oceans. This method of removal of the orbital debris will enable safer passage for future human-crewed missions into space.

Keywords: altitude, Kessler syndrome, laser ablation, Newton’s third law of motion, satellites, Space debris

Procedia PDF Downloads 143

Authors: Sophie Mills, Leila L. Touil, Richard Sisson

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Introduction: The TNM classification is the global standard for the staging of head and neck cancers. Accurate clinical-radiological staging of tumours (cTNM) is essential to predict prognosis, facilitate surgical planning and determine the need for other therapeutic modalities. This study aims to determine the accuracy of pre-operative cTNM staging using pathological TNM (pTNM) and consider possible causes of TNM stage migration, noting any variation throughout the COVID-19 pandemic. Materials and Methods: A retrospective cohort study examined records of patients with surgical management of head and neck cancer at a tertiary head and neck centre from November 2019 to November 2020. Data was extracted from Somerset Cancer Registry and histopathology reports. cTNM and pTNM were compared before and during the first wave of COVID-19, as well as with other potential prognostic factors such as tumour site and tumour stage. Results: 119 cases were identified, of which 52.1% (n=62) were male, and 47.9% (n=57) were female with a mean age of 67 years. Clinical and pathological staging differed in 54.6% (n=65) of cases. Of the patients with stage migration, 40.4% (n=23) were up-staged and 59.6% (n=34) were down-staged compared with pTNM. There was no significant difference in the accuracy of cTNM staging compared with age, sex, or tumour site. There was a statistically highly significant (p < 0.001) correlation between cTNM accuracy and tumour stage, with the accuracy of cTNM staging decreasing with the advancement of pTNM staging. No statistically significant variation was noted between patients staged prior to and during COVID-19. Conclusions: Discrepancies in staging can impact management and outcomes for patients. This study found that the higher the pTNM, the more likely stage migration will occur. These findings are concordant with the oncology literature, which highlights the need to improve the accuracy of cTNM staging for more advanced tumours.

Keywords: COVID-19, head and neck cancer, stage migration, TNM staging

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Authors: Li-Kai Kuo, Shyh-Hau Wang

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The kinetic trajectory of the median nerve (MN) in the wrist has shown to be capable of being applied to assess the carpal tunnel syndrome (CTS), and was found able to be detected by high-frequency ultrasound image via motion tracking technique. Yet, previous study may not quickly perform the measurement due to the use of a single element transducer for ultrasound image scanning. Therefore, previous system is not appropriate for being applied to clinical application. In the present study, B-mode ultrasound images of the wrist corresponding to movements of fingers from flexion to extension were acquired by clinical applicable real-time scanner. The kinetic trajectories of MN were off-line estimated utilizing two dimensional Baysian speckle tracking (TDBST) technique. The experiments were carried out from ten volunteers by ultrasound scanner at 12 MHz frequency. Results verified from phantom experiments have demonstrated that TDBST technique is able to detect the movement of MN based on signals of the past and present information and then to reduce the computational complications associated with the effect of such image quality as the resolution and contrast variations. Moreover, TDBST technique tended to be more accurate than that of the normalized cross correlation tracking (NCCT) technique used in previous study to detect movements of the MN in the wrist. In response to fingers’ flexion movement, the kinetic trajectory of the MN moved toward the ulnar-palmar direction, and then toward the radial-dorsal direction corresponding to the extensional movement. TDBST technique and the employed ultrasound image scanner have verified to be feasible to sensitively detect the kinetic trajectory and displacement of the MN. It thus could be further applied to diagnose CTS clinically and to improve the measurements to assess 3D trajectory of the MN.

Keywords: baysian speckle tracking, carpal tunnel syndrome, median nerve, motion tracking

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Authors: Farid Risheq, M. Zaid Alrisheq, Shuaa Al-Sadoon, Karim Al-Faqih, Mays Abdulazeez

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Breast cancer is the most frequently diagnosed cancer worldwide, and a common cause of death among women. Various conventional anatomical imaging tools are utilized for diagnosis, histological assessment and TNM (Tumor, Node, Metastases) staging of breast cancer. Biopsy of sentinel lymph node is becoming an alternative to the axillary lymph node dissection. Advances in 18-Fluoro-Deoxi-Glucose Positron Emission Tomography/Computed Tomography (18FDG-PET/CT) imaging have facilitated breast cancer diagnosis utilizing biological trapping of 18FDG inside lesion cells, expressed as Standardized Uptake Value (SUVmax). Objective: To present the utility of 18FDG uptake PET/CT scans in detecting active extra lymph nodes and distant occult metastases for breast cancer staging. Subjects and Methods: Four female patients were presented with initially classified TNM stages of breast cancer based on conventional anatomical diagnostic techniques. 18FDG-PET/CT scans were performed one hour post 18FDG intra-venous injection of (300-370) MBq, and (7-8) bed/130sec. Transverse, sagittal, and coronal views; fused PET/CT and MIP modality were reconstructed for each patient. Results: A total of twenty four lesions in breast, extended lesions to lung, liver, bone and active extra lymph nodes were detected among patients. The initial TNM stage was significantly changed post 18FDG-PET/CT scan for each patient, as follows: Patient-1: Initial TNM-stage: T1N1M0-(stage I). Finding: Two lesions in right breast (3.2cm2, SUVmax=10.2), (1.8cm2, SUVmax=6.7), associated with metastases to two right axillary lymph nodes. Final TNM-stage: T1N2M0-(stage II). Patient-2: Initial TNM-stage: T2N2M0-(stage III). Finding: Right breast lesion (6.1cm2, SUVmax=15.2), associated with metastases to right internal mammary lymph node, two right axillary lymph nodes, and sclerotic lesions in right scapula. Final TNM-stage: T2N3M1-(stage IV). Patient-3: Initial TNM-stage: T2N0M1-(stage III). Finding: Left breast lesion (11.1cm2, SUVmax=18.8), associated with metastases to two lymph nodes in left hilum, and three lesions in both lungs. Final TNM-stage: T2N2M1-(stage IV). Patient-4: Initial TNM-stage: T4N1M1-(stage III). Finding: Four lesions in upper outer quadrant area of right breast (largest: 12.7cm2, SUVmax=18.6), in addition to one lesion in left breast (4.8cm2, SUVmax=7.1), associated with metastases to multiple lesions in liver (largest: 11.4cm2, SUV=8.0), and two bony-lytic lesions in left scapula and cervicle-1. No evidence of regional or distant lymph node involvement. Final TNM-stage: T4N0M2-(stage IV). Conclusions: Our results demonstrated that 18FDG-PET/CT scans had significantly changed the TNM stages of breast cancer patients. While the T factor was unchanged, N and M factors showed significant variations. A single session of PET/CT scan was effective in detecting active extra lymph nodes and distant occult metastases, which were not identified by conventional diagnostic techniques, and might advantageously replace bone scan, and contrast enhanced CT of chest, abdomen and pelvis. Applying 18FDG-PET/CT scan early in the investigation, might shorten diagnosis time, helps deciding adequate treatment protocol, and could improve patients’ quality of life and survival. Trapping of 18FDG in malignant lesion cells, after a PET/CT scan, increases the retention index (RI%) for a considerable time, which might help localize sentinel lymph node for biopsy using a hand held gamma probe detector. Future work is required to demonstrate its utility.

Keywords: axillary lymph nodes, breast cancer staging, fluorodeoxyglucose positron emission tomography/computed tomography, lymph nodes

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Authors: Gonzalo Ortiz de Elguea-Culebras, Raúl Sánchez-Vioquea, Adela Mena-Morales, Manuel Alaiz, Enrique Melero-Bravo, Esteban García-Romero, Javier Vioque, Lourdes Marchante-Cuevas, Julio Girón-Calle

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Saffron (Crocus sativus L.) is a highly valued crop for the manufacture of spice that consists of the dried stigma of the flowers. This is in contrast to other underutilized parts of the saffron plant as leaves, which represent abundant biomass whose use might help to enhance the sustainability of the saffron crop. Saffron leaves contain significant amounts of phenolic compounds, 7.8 equivalent grams of gallic acid per 100g of extract, and are very promising compounds in terms of exploring novel uses of saffron leaves. Given that phenolic compounds have numerous effects on cancer-related biological pathways, we have investigated the in vitro antiproliferative effect of saffron leaf polyphenols against human colon adenocarcinoma cells (Caco-2). Polyphenols were extracted from leaves with 70% ethanol, defatted with hexane, and purified by solid phase extraction using C18 silica gel and then silica gel 60. Analysis of polyphenols was performed by HPLC-ESI-MS. Di-, tri-, and tetrahexosides of quercetin, kaempferol, and isorhamnetin, as well as C-hexosides like isoorientin and vitexin, were tentatively identified. Polyphenols strongly inhibited the proliferation of Caco-2 cells, which is consistent with model studies in which several of the polyphenols identified in saffron leaves have demonstrated their potential as chemopreventive agents in cancer. Due to the low profitability that saffron leaf currently represents, we consider these results very encouraging and that this by-product deserves further investigation as a potential source of active molecules against colorectal cancer.

Keywords: saffron leaves, agricultural by-products, polyphenols, antiproliferative effect, human colon adenocarcinoma cells

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Authors: Aihong Zhao, Priya Sastry, Mark L Field, Mohamad Bashir, Arvind Singh, David Richens

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Objectives: Intramural haematoma (IMH) is one of the pathologies, along with acute aortic dissection, that present as Acute Aortic Syndrome (AAS). Evidence suggests that unlike aortic dissection, some intramural haematomas may regress with medical management. However, intramural haematomas have been traditionally managed like acute aortic dissections. Given that some of these pathologies may regress with conservative management, it would be useful to be able to identify which of these may not need high risk emergency intervention. A computational aortic model was used in this study to try and identify intramural haematomas with risk of progression to aortic dissection. Methods: We created a computational model of the aorta with luminal blood flow. Reports in the literature have identified 11 mm as the radial clot thickness that is associated with heightened risk of progression of intramural haematoma. Accordingly, haematomas of varying sizes were implanted in the modeled aortic wall to test this hypothesis. The model was exposed to physiological blood flows and the stresses and strains in each layer of the aortic wall were recorded. Results: Size and shape of clot were seen to affect the magnitude of aortic stresses. The greatest stresses and strains were recorded in the intima of the model. When the haematoma exceeded 10 mm in all dimensions, the stress on the intima reached breaking point. Conclusion: Intramural clot size appears to be a contributory factor affecting aortic wall stress. Our computer simulation corroborates clinical evidence in the literature proposing that IMH diameter greater than 11 mm may be predictive of progression. This preliminary report suggests finite element modelling of the aortic wall may be a useful process by which to examine putative variables important in predicting progression or regression of intramural haematoma.

Keywords: intramural haematoma, acute aortic syndrome, finite element analysis,

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Authors: Ning Li, Jiacheng Zhang, Zheng Yang, Sylvia Kang

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Introduction: Polycystic ovary syndrome (PCOS) is a common physiological symptom in women of reproductive age. Women with PCOS may have infrequent or prolonged menstrual periods and excess male hormone (androgen) levels. Mira analyzes the cycle profiles and the luteinizing hormone (LH) changes in urine, closely related to the fertility level of healthy women and PCOS women. From the difference between the two groups, Mira helps to understand the physiological state of PCOS women and their hormonal changes in the menstrual cycle. Methods: In this study, data from 1496 cycles and information from 342 women belonging to two groups (181 PCOS and 161 Healthy) were collected and analyzed. Women test their luteinizing hormone (LH) in urine daily with Mira fertility test wand and Mira analyzer, from the day after the menstruation to the starting day of the next menstruation. All the collected data meets Mira’s user agreement and users’ identification was removed. The cycle length, LH peak, and other cycle information of the PCOS group were compared with the Healthy group. Results: The average cycle length of PCOS women is 41 days and of the Healthy women is 33 days. 91.4% of cycle length is within 40 days for the Healthy group, while it decreases to 71.9% for the PCOS group. This means PCOS women have a longer menstrual cycle and more variation during the cycle. With more variation, the ovulation prediction becomes more difficult for the PCOS group. The deviation between the LH surge day and the predicted ovulation day, calculated by the starting day of the next menstruation minus 14 days, is greater in the PCOS group compared with the Healthy group. Also, 46.96% of PCOS women have an irregular cycle, and only 19.25% of healthy women show an irregular cycle. Conclusion: PCOS women have longer menstrual cycles and more variation during the menstrual cycles. The traditional ovulation prediction is not suitable for PCOS women.

Keywords: menstrual cycle, PCOS, urinary luteinizing hormone, Mira

Procedia PDF Downloads 175

Authors: Katarzyna Lubecka, Kirsty Flower, Megan Beetch, Lucinda Kurzava, Hannah Buvala, Samer Gawrieh, Suthat Liangpunsakul, Tracy Gonzalez, George McCabe, Naga Chalasani, James M. Flanagan, Barbara Stefanska

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Hepatocellular carcinoma (HCC), the most prevalent type of primary liver cancer, is the second leading cause of cancer death worldwide. Late onset of clinical symptoms in HCC results in late diagnosis and poor disease outcome. Approximately 85% of individuals with HCC have underlying liver cirrhosis. However, not all cirrhotic patients develop cancer. Reliable early detection biomarkers that can distinguish cirrhotic patients who will develop cancer from those who will not are urgently needed and could increase the cure rate from 5% to 80%. We used Illumina-450K microarray to test whether blood DNA, an easily accessible source of DNA, bear site-specific changes in DNA methylation in response to HCC before diagnosis with conventional tools (pre-diagnostic). Top 11 differentially methylated sites were selected for validation by pyrosequencing. The diagnostic potential of the 11 pyrosequenced probes was tested in blood samples from a prospective cohort of cirrhotic patients. We identified 971 differentially methylated CpG sites in pre-diagnostic HCC cases as compared with healthy controls (P < 0.05, paired Wilcoxon test, ICC ≥ 0.5). Nearly 76% of differentially methylated CpG sites showed lower levels of methylation in cases vs. controls (P = 2.973E-11, Wilcoxon test). Classification of the CpG sites according to their location relative to CpG islands and transcription start site revealed that those hypomethylated loci are located in regulatory regions important for gene transcription such as CpG island shores, promoters, and 5’UTR at higher frequency than hypermethylated sites. Among 735 CpG sites hypomethylated in cases vs. controls, 482 sites were assigned to gene coding regions whereas 236 hypermethylated sites corresponded to 160 genes. Bioinformatics analysis using GO, KEGG and DAVID knowledgebase indicate that differentially methylated CpG sites are located in genes associated with functions that are essential for gene transcription, cell adhesion, cell migration, and regulation of signal transduction pathways. Taking into account the magnitude of the difference, statistical significance, location, and consistency across the majority of matched pairs case-control, we selected 11 CpG loci corresponding to 10 genes for further validation by pyrosequencing. We established that methylation of CpG sites within 5 out of those 10 genes distinguish cirrhotic patients who subsequently developed HCC from those who stayed cancer free (cirrhotic controls), demonstrating potential as biomarkers of early detection in populations at risk. The best predictive value was detected for CpGs located within BARD1 (AUC=0.70, asymptotic significance ˂0.01). Using an additive logistic regression model, we further showed that 9 CpG loci within those 5 genes, that were covered in pyrosequenced probes, constitute a panel with high diagnostic accuracy (AUC=0.887; 95% CI:0.80-0.98). The panel was able to distinguish pre-diagnostic cases from cirrhotic controls free of cancer with 88% sensitivity at 70% specificity. Using blood as a minimally invasive material and pyrosequencing as a straightforward quantitative method, the established biomarker panel has high potential to be developed into a routine clinical test after validation in larger cohorts. This study was supported by Showalter Trust, American Cancer Society (IRG#14-190-56), and Purdue Center for Cancer Research (P30 CA023168) granted to BS.

Keywords: biomarker, DNA methylation, early detection, hepatocellular carcinoma

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Authors: Aleksandra Chałupnik, Zuzanna Chilimoniuk, Joanna Borowik, Aleksandra Borkowska, Anna Torres

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Background: Precocious puberty is the occurrence of secondary sexual characteristics in girls before the age of 8. The diverse etiology of premature puberty is crucial to determine whether it is true precocious puberty, depending on the activation of the hypothalamic-pituitary-gonadal axis, or pseudo-precocious, which is independent of the activation of this axis. Whatever the cause, premature action of the sex hormones leads to the common symptoms of various forms of puberty. These include the development of sexual characteristics, acne, acceleration of growth rate and acceleration of skeletal maturation. Due to the possible genetic basis of the disorders, an interdisciplinary search for the cause is needed. Case report: The case report concerns a patient of a pediatric gynecology clinic who, at the age of two years, developed advanced thelarhe (M3) and started recurrent vaginal bleeding. In August 2019, gonadotropin suppression initially and after LHRH stimulation and high estradiol levels were reported at the Endocrinology Department. Imaging examinations showed a cyst in the right ovary projection. The bone age was six years. The entire clinical picture indicated pseudo- (peripheral) precocious in the course of ovarian autonomic cyst. In the follow-up ultrasound performed in September, the image of the cyst was stationary and normalization of estradiol levels and clinical symptoms was noted. In December 2019, cyst regression and normal gonadotropin and estradiol concentrations were found. In June 2020, white mucus tinged with blood on the underwear, without any other disturbing symptoms, was observed for several days. Two consecutive USG examinations carried out in the same month confirmed the change in the right ovary, the diameter of which was 25 mm with a very high level of estradiol. Germinal tumor markers were normal. On the Tanner scale, the patient scored M2P1. The labia and hymen had puberty features. The correct vaginal entrance was visible. Another active vaginal bleeding occurred in the first week of July 2020. The considered laparoscopic treatment was abandoned due to the lack of oncological indications. Treatment with Tamoxifen was recommended in July 2020. In the initiating period of treatment, no maturation progression, and even reduction of symptoms, no acceleration of growth and a marked reduction in the size of the cysts were noted. There was no bleeding. After the size of the cyst and hormonal activity increased again, the treatment was changed to Anastrozole, the effect of which led to a reduction in the size of the cyst. Conclusions: The entire clinical picture indicates alleged (peripheral) puberty. Premature puberty in girls, which is manifested as enlarged mammary glands with high levels of estrogens secreted by autonomic ovarian cysts and prepubertal levels of gonadotropins, may indicate McCune-Albright syndrome. Vaginal bleeding may also occur in this syndrome. Cancellation of surgical treatment of the cyst made it impossible to perform a molecular test that would allow to confirm the diagnosis. Taking into account the fact that cysts are often one of the first symptoms of McCune-Albrigt syndrome, it is important to remember about multidisciplinary care for the patient and careful search for skin and bone changes or other hormonal disorders.

Keywords: McCune Albrigth's syndrome, ovarian cyst, pediatric gynaecology, precocious puberty

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Authors: Mohammad Alkhatatbeh, Nehad Ayoub, Nizar Mhaidat, Nesreen Saadeh, Lisa Lincz

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CD36 is involved in the development of atherosclerosis by enhancing macrophage endocytosis of oxidized-low density lipoproteins and foam cell formation. Soluble CD36 (sCD36) was found to be elevated in type 2 diabetic patients and was supposed to act as a marker of insulin resistance and atherosclerosis. In young subjects, sCD36 was associated with cardiovascular risk factors including obesity and hypertriglyceridemia. This study was conducted to further investigate the relationship between plasma sCD36 and cardiovascular risk factors among middle-aged patients with metabolic syndrome (MetS) and healthy controls. SCD36 concentrations were determined by enzyme-linked immunosorbent assays (ELISA) for 41 patients with MetS and 36 healthy controls. Data for other variables were obtained from patients' medical records. SCD36 concentrations were relatively low compared to most other studies and were not significantly different between the MetS group and controls (P-value=0.17). SCD36 was also not correlated with age, body mass index, glucose, lipid profile, serum electrolytes and blood counts. SCD36 was not significantly different between subjects with obesity, hyperglycemia, dyslipidemia, hypertension or cardiovascular disease and those without these abnormalities (P-value > 0.05). The inconsistency between results reported in this study and other studies may be unique to the study population or be a result of the lack of a reliable standardized method for determining absolute sCD36 concentrations. However, further investigations are required to assess CD36 tissue expression in the study population and to assess the accuracy of various commercially available sCD36 ELISA kits. Thus, the availability of a standardized simple sCD36 ELISA that could be performed in any basic laboratory would be more favorable to the specialized flow cytometry methods that detect CD36+ microparticles if it was to be used as a biomarker.

Keywords: metabolic syndrome, CD36, cardiovascular risk, obesity, type 2 diabetes mellitus

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Authors: Gurbanova J., Majidova N., Ali-Zade S., Hasanova A., Mikailzade P.

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Currently, the problem of oncogynecological diseases is widespread and remains relevant in terms of quantitative growth. It is known that due to the increase in the number of benign diseases of the cervix, the development of precancerous conditions occurs. Benign diseases of the cervix represent the most common gynecological problem, which are often precursors of malignant neoplasms, especially cervical cancer. According to statistics, benign diseases of the cervix cover 25-45% of all gynecological diseases. Among women's oncogynecological diseases, cervical cancer ranks second in the world after breast cancer and ranks first in the mortality rate among oncological diseases in economically underdeveloped countries. We performed a comprehensive clinical and laboratory examination of 130 women aged 18 to 73 with benign cervical diseases. 59 (38.5%) women of reproductive age, as well as 39 (30%) premenopausal and 41 (31.5%) menopausal patients, participated in the study. Detailed anamnesis was collected from all patients, objective and gynecological examination was performed, laboratory and instrumental examinations (USM, IPV DNA, smear microscopy, and PCR bacteriological examination of sexually transmitted infections), simple and extended colposcopy, liquid-based РАР-smear smear and РАР-classic smear examinations were conducted. As a result of the research, the following nosological forms were found in women with benign diseases of the cervix: non-specific vaginitis in 10 (7.7%) cases; ectopia, endocervicitis - 60(46.2%); cervical ectropion - 7(5.4%); cervical polyp - 9(6.9%); cervical leukoplakia - 15(11.5%); atrophic vaginitis - 7(5.4%); condyloma - 12(9.2%); cervical stenosis - 2(1.5%); endometriosis of the cervix - was noted in 8 (6.2%) cases (p<0.001), respectively. Characteristics of the menstrual cycle among the examined women: normal cycle in 97 (74.6%) cases; oligomenorrhea – 23 (17.7%); polymenorrhea – 4(3.1%); algomenorrhea – noted in 6 (4.6%) cases (p<0.001). Cytological examination showed that: the specificity of liquid-based cytology was 76.2%, and the traditional PAP test was set at 70.6%. The overall diagnostic value was calculated to be 86% in liquid-based cytology and 78.5% in conventional PAP tests. Treatment of women with benign diseases of the cervix was carried out by diathermocoagulation method and "FOTEK EA 141M" device. It should be noted that 6 months after the treatment, after treatment with the "FOTEK EA 141M" device, there was no relapse in any patient. Recurrence was found in 23.7% of patients after diathermoelectrocoagulation. Thus, it is clear from the above that the study of cervical pathologies, the determination of optimal examinations, and effective treatment methods is one of the urgent problems facing obstetrics and gynecology.

Keywords: cervical cancer, cytological examination, PAP-smear, non-specific vaginitis

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Authors: Hanan Alsaeid Alshenawy

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Background: Cervical dysplasia, which is potentially precancerous, has increased in young women. Detection of cervical is important for reducing morbidity and mortality in cervical cancer. This study analyzes the immunohistochemical expression of p16, HPV L1 capsid protein and Ki67 in cervical intraepithelial lesions and correlates them with lesion grade to develop a set of markers for diagnosis and detect the prognosis of cervical cancer precursors. Methods: 75 specimens were analyzed including 15 cases CIN 1, 28 CIN 2, 20 CIN 3, and 12 cervical squamous carcinoma, besides 10 normal cervical tissues. They were stained for p16, HPV L1 and Ki-67. Sensitivity, specificity, predictive values and accuracy were evaluated for each marker. Results: p16 expression increased during the progression from CIN 1 to carcinoma. HPV L1 positivity was detected in CIN 2 and decreased gradually as the CIN grade increased but disappear in carcinoma. Strong Ki-67 expression was observed with high grades CIN and carcinoma. p16, HPV L1 and Ki67 were sensitive but with variable specificity in detecting CIN lesions. Conclusions: p16, HPV L1 and Ki67 are useful set of markers in establishing the risk of high-grade CIN. They complete each other to reach accurate diagnosis and prognosis.

Keywords: p16, HPV L1, Ki67, CIN, cervical carcinoma

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Authors: Suman Chaudhary, Rupinder K. Kanwar, Jagat R. Kanwar

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Azadirachta indica, also known as Neem belonging to the mahogany family is actively gaining interest in the era of modern day medicine due to its extensive applications in homeopathic medicine such as Ayurveda and Unani. More than 140 phytochemicals have been extracted from neem leaves, seed, bark and flowers for agro-medicinal applications. Among the various components, neem leaf protein (NLP) is currently the most investigated active ingredient, due to its immunomodulatory activities against tumor growth. However, these therapeutic ingredients of neem are susceptible to degradation and cannot withstand the drastic pH changes under physiological environment, and therefore, there is an urgent need of an alternative strategy such as a nano-delivery system to exploit its medicinal benefits. This study hypothesizes that guar gum (GG) derived biodegradable nano-carrier based encapsulation of NLP will improve its stability, specificity and sensitivity, thus facilitating targeted anti-cancer therapeutics. GG is a galactomannan derived from the endosperm of the guar beans seeds. Synthesis of guar nanocapsules (NCs) was performed using nanoprecipitation technique where the GG was encapsulated with NLP. Preliminary experiments conducted to characterize the NCs confirmed spherical morphology with a narrow size distribution of 30-40 nm. Differential scanning colorimetric analysis (DSC) validated the stability of these NCs even at a temperature range of 50-60°C which was well within the physiological and storage conditions. Thermogravimetric (TGA) analysis indicated high decomposition temperature of these NCs ranging upto 350°C. Additionally, Fourier Transform Infrared spectroscopy (FTIR) and the SDS-PAGE data acquired confirmed the successful encapsulation of NLP in the NCs. The anti-cancerous therapeutic property of this NC was tested on colon cancer cells (caco-2) as they are one of the most prevalent form of cancer. These NCs (both NLP loaded and void) were also tested on human intestinal epithelial cells (FHs 74) cells to evaluate their effect on normal cells. Cytotoxicity evaluation of the NCs in the cell lines confirmed that the IC50 for NLP in FHs 74 cells was ~2 fold higher than in caco-2 cells, indicating that this nanoformulation system possessed biocompatible anti-cancerous properties Immunoconfocal microscopy analysis confirmed the time dependent internalization of the NCs within 6h. Recent findings performed using Annexin V and PI staining indicated a significant increase (p ≤ 0.001) in the early and late apoptotic cell population when treated with the NCs signifying the role of NLP in inducing apoptosis in caco-2 cells. This was further validated using Western blot, Polymerase chain reaction (PCR) and Fluorescence activated cell sorter (FACS) aided protein expressional analysis which presented a downregulation of survivin, an anti-apoptotic cell marker and upregulation of Bax/Bcl-2 ratio (pro-apoptotic indicator). Further, both the NLP NC and unencapsulated NLP treatment destabilized the mitochondrial membrane potential subsequently facilitating the release of the pro-apoptotic caspase cascade initiator, cytochrome-c. Future studies will be focused towards granting specificity to these NCs towards cancer cells, along with a comprehensive analysis of the anti-cancer potential of this naturally occurring compound in different cancer and in vivo animal models, will validate the clinical application of this unprecedented protein therapeutic.

Keywords: anti-tumor, guar gum, nanocapsules, neem leaf protein

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Authors: Sinead Morrison, Ann Swillen, Therese Van Amelsvoort, Samuel Chawner, Elfi Vergaelen, Michael Owen, Marianne Van Den Bree

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22q11.2 Deletion Syndrome (22q11.2DS) is caused by the deletion of approximately 60 genes on chromosome 22 and is associated with high rates of neurodevelopmental disorders such as Attention Deficit Hyperactivity Disorder (ADHD) and Autism Spectrum Disorders (ASD). The presentation of these disorders in 22q11.2DS is reported to be comparable to idiopathic forms and therefore presents a valuable model for understanding mechanisms of neurodevelopmental disorders. Cognitive deficits are thought to be a core feature of neurodevelopmental disorders, and possibly manifest in behavioural and emotional problems. There have been mixed findings in 22q11.2DS on whether the presence of ADHD or ASD is associated with greater cognitive deficits. Furthermore, the influence of developmental stage has never been taken into account. The aim was therefore to examine whether the presence of ADHD or ASD was associated with cognitive deficits in childhood and/or adolescence in 22q11.2DS. We conducted the largest study to date of this kind in 22q11.2DS. The same battery of tasks measuring processing speed, attention and spatial working memory were completed by 135 participants with 22q11.2DS. Wechsler IQ tests were completed, yielding Full Scale (FSIQ), Verbal (VIQ) and Performance IQ (PIQ). Age-standardised difference scores were produced for each participant. Developmental stages were defined as children (6-10 years) and adolescents (10-18 years). ADHD diagnosis was ascertained from a semi-structured interview with a parent. ASD status was ascertained from a questionnaire completed by a parent. Interaction and main effects of cognitive performance of those with or without a diagnosis of ADHD or ASD in childhood or adolescence were conducted with 2x2 ANOVA. Significant interactions were followed up with t-tests of simple effects. Adolescents with ASD displayed greater deficits in all measures (processing speed, p = 0.022; sustained attention, p = 0.016; working memory, p = 0.006) than adolescents without ASD; there was no difference between children with and without ASD. There were no significant differences on IQ measures. Both children and adolescents with ADHD displayed greater deficits on sustained attention (p = 0.002) than those without ADHD. There were no significant differences on any other measures for ADHD. Magnitude of cognitive deficit in individuals with 22q11.2DS varied by cognitive domain, developmental stage and presence of neurodevelopmental disorder. Adolescents with 22q11.2DS and ASD showed greater deficits on all measures, which suggests there may be a sensitive period in childhood to acquire these domains, or reflect increasing social and academic demands in adolescence. The finding of poorer sustained attention in children and adolescents with ADHD supports previous research and suggests a specific deficit which can be separated from processing speed and working memory. This research provides unique insights into the association of ASD and ADHD with cognitive deficits in a group at high genomic risk of neurodevelopmental disorders.

Keywords: 22q11.2 deletion syndrome, attention deficit hyperactivity disorder, autism spectrum disorder, cognitive development

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Authors: Yogesh Rai, Saurabh Singh, Sanjay Pandey, Dhananjay K. Sah, B. G. Roy, B. S. Dwarakanath, Anant N. Bhatt

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One of the most common signatures of highly malignant gliomas is their capacity to metabolize more glucose to lactic acid than normal brain tissues, even under normoxic conditions (Warburg effect), indicating that aerobic glycolysis is constitutively upregulated through stable genetic or epigenetic changes. However, oxidative phosphorylation (OxPhos) is also required to maintain the mitochondrial membrane potential for tumor cell survival. In the process of tumorigenesis, tumor cells during fastest growth rate exhibit both high glycolytic and high OxPhos. Therefore, metabolically reprogrammed cancer cells with combination of both aerobic glycolysis and altered OxPhos develop a robust metabolic phenotype, which confers a selective growth advantage. In our study, we grew the high glycolytic BMG-1 (glioma) cells with continuous exposure of mitochondrial uncoupler 2, 4, dinitro phenol (DNP) for 10 passages to obtain a phenotype of high glycolysis with enhanced altered OxPhos. We found that OxPhos modified BMG (OPMBMG) cells has similar growth rate and cell cycle distribution but high mitochondrial mass and functional enzymatic activity than parental cells. In in-vitro studies, OPMBMG cells showed enhanced invasion, proliferation and migration properties. Moreover, it also showed enhanced angiogenesis in matrigel plug assay. Xenografted tumors from OPMBMG cells showed reduced latent period, faster growth rate and nearly five folds reduction in the tumor take in nude mice compared to BMG-1 cells, suggesting that robust metabolic phenotype facilitates tumor formation and growth. OPMBMG cells which were found radio-resistant, showed enhanced radio-sensitization by 2-DG as compared to the parental BMG-1 cells. This study suggests that metabolic reprogramming in cancer cells enhances the potential of migration, invasion and proliferation. It also strengthens the cancer cells to escape the death processes, conferring resistance to therapeutic modalities. Our data also suggest that combining metabolic inhibitors like 2-DG with conventional therapeutic modalities can sensitize such metabolically aggressive cancer cells more than the therapies alone.

Keywords: 2-DG, BMG, DNP, OPM-BMG

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Authors: M. Chaichanyut, S. Tungjitkusolmun

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This paper is concerned with microwave (MW) ablation for a liver cancer tissue by using helix antenna. The antenna structure supports the propagation of microwave energy at 2.45 GHz. A 1½ turn spiral catheter-based microwave antenna applicator has been developed. We utilize the three-dimensional finite element method (3D FEM) simulation to analyze where the tissue heat flux, lesion pattern and volume destruction during MW ablation. The configurations of helix antenna where Helix air-core antenna and Helix Dielectric-core antenna. The 3D FEMs solutions were based on Maxwell and bio-heat equations. The simulation protocol was power control (10 W, 300s). Our simulation result, both helix antennas have heat flux occurred around the helix antenna and that can be induced the temperature distribution similar (teardrop). The region where the temperature exceeds 50°C the microwave ablation was successful (i.e. complete destruction). The Helix air-core antenna and Helix Dielectric-core antenna, ablation zone or axial ratios (Widest/length) were respectively 0.82 and 0.85; the complete destructions were respectively 4.18 cm³ and 5.64 cm³.

Keywords: liver cancer, Helix antenna, finite element, microwave ablation

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Authors: Ilana Singer, Anastasia Lučić, Julie Leclerc

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Introduction: Tics, characterized by repetitive, sudden, non-voluntary motor movements or vocalizations, are prevalent in chronic tic disorder (CT) and Tourette Syndrome (TS). These neurodevelopmental disorders often coexist with various psychiatric conditions, leading to challenges and reduced quality of life. While medication in conjunction with behavioral interventions, such as Habit Reversal Training (HRT), Exposure Response Prevention (ERP), and Comprehensive Behavioral Intervention for Tics (CBIT), has shown efficacy, a significant proportion of patients experience persistent tics. Thus, innovative treatment approaches are necessary to improve therapeutic outcomes, such as mindfulness-based approaches. Nonetheless, the effectiveness of mindfulness-based interventions in the context of CT and TS remains understudied. Objective: The objective of this scoping review is to provide an overview of the current state of research on mindfulness-based interventions for CT and TS, identify knowledge and evidence gaps, discuss the effectiveness of mindfulness-based interventions with other treatment options, and discuss implications for clinical practice and policy development. Method: Using guidelines from Peters (2020) and the PRISMA-ScR, a scoping review was conducted. Multiple electronic databases were searched from inception until June 2023, including MEDLINE, EMBASE, PsychInfo, Global Health, PubMed, Web of Science, and Érudit. Inclusion criteria were applied to select relevant studies, and data extraction was independently performed by two reviewers. Results: Five papers were included in the study. Firstly, we found that mindfulness interventions were found to be effective in reducing anxiety and depression while enhancing overall well-being in individuals with tics. Furthermore, the review highlighted the potential role of mindfulness in enhancing functional connectivity within the Default Mode Network (DMN) as a compensatory function in TS patients. This suggests that mindfulness interventions may complement and support traditional therapeutic approaches, particularly HRT, by positively influencing brain networks associated with tic regulation and control. Conclusion: This scoping review contributes to the understanding of the effectiveness of mindfulness-based interventions in managing CT and TS. By identifying research gaps, this review can guide future investigations and interventions to improve outcomes for individuals with CT or TS. Overall, these findings emphasize the potential benefits of incorporating mindfulness-based interventions as a smaller subset within comprehensive treatment strategies. However, it is essential to acknowledge the limitations of this scoping review, such as the exclusion of a pre-established protocol and the limited number of studies available for inclusion. Further research and clinical exploration are necessary to better understand the specific mechanisms and optimal integration of mindfulness-based interventions with existing behavioral interventions for this population.

Keywords: scoping reviews, Tourette Syndrome, tics, mindfulness-based, therapy, intervention

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Authors: S. Fahiminiya, J. Nadaf, F. Rauch, L. Jerome-Majewska, J. Majewski

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Background: Sequencing of protein coding regions of human genome (Whole Exome Sequencing; WES), has demonstrated a great success in the identification of causal mutations for several rare genetic disorders in human. Generally, most of WES studies have focused on rare variants in coding exons and splicing-sites where missense substitutions lead to the alternation of protein product. Although focusing on this category of variants has revealed the mystery behind many inherited genetic diseases in recent years, a subset of them remained still inconclusive. Here, we present the result of our WES studies where analyzing only rare variants in coding regions was not conclusive but further investigation revealed the involvement of non-coding variants and copy number variations (CNV) in etiology of the diseases. Methods: Whole exome sequencing was performed using our standard protocols at Genome Quebec Innovation Center, Montreal, Canada. All bioinformatics analyses were done using in-house WES pipeline. Results: To date, we successfully identified several disease causing mutations within gene coding regions (e.g. SCARF2: Van den Ende-Gupta syndrome and SNAP29: 22q11.2 deletion syndrome) by using WES. In addition, we showed that variants in non-coding regions and CNV have also important value and should not be ignored and/or filtered out along the way of bioinformatics analysis on WES data. For instance, in patients with osteogenesis imperfecta type V and in patients with glucocorticoid deficiency, we identified variants in 5'UTR, resulting in the production of longer or truncating non-functional proteins. Furthermore, CNVs were identified as the main cause of the diseases in patients with metaphyseal dysplasia with maxillary hypoplasia and brachydactyly and in patients with osteogenesis imperfecta type VII. Conclusions: Our study highlights the importance of considering non-coding variants and CNVs during interpretation of WES data, as they can be the only cause of disease under investigation.

Keywords: whole exome sequencing data, non-coding variants, copy number variations, rare diseases

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Authors: Sema Şenoğlu, Sevgi Karakuş

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Hydrazone scaffold is important to design new drug groups and is found to possess numerous uses in pharmaceutical chemistry. Besides, hydrazone derivatives are also known for biological activities such as anticancer, antimicrobial, antiviral, and antifungal. Hydrazone derivatives are promising anticancer agents because they inhibit cancer proliferation and induce apoptosis. Human carbonic anhydrase IX has a high potential to be an antiproliferative drug target, and targeting this protein is also important for obtaining potential anticancer inhibitors. The protein construct was retrieved as a PDB file from the RCSB protein database. This binding interaction of proteins and ligands was performed using Discovery Studio Visualizer. In vitro inhibitory activity of hydrazone derivatives was tested against enzyme carbonic anhydrase IX on the PyRx programme. Most of these molecules showed remarkable human carbonic anhydrase IX inhibitory activity compared to the acetazolamide. As a result, these compounds appear to be a potential target in drug design against human carbonic anhydrase IX.

Keywords: cancer, carbonic anhydrase IX enzyme, docking, hydrazone

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Authors: Saboor Saeed, Chunming Jiang

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Eosinophilic Granulomatosis with polyangiitis (EGPA), formerly known as Churg-Strauss syndrome, is a rare systemic vasculitis of small and medium-sized vessels that primarily develops in middle-aged individuals. It is characterized by asthma, blood eosinophilia, and extra pulmonary manifestations. In childhood, EGPA is extremely rare. Pulmonary and cardiac involvement is predominant in pediatric EGPA, and mortality is substantial. Generally, EGPA will develop in three stages: a) The allergic phase is commonly associated with asthma, allergic rhinitis, and sinusitis, b) the eosinophilic phase, in which the main pathology is related to the infiltration of eosinophilic organs, i.e., lung, heart, and gastrointestinal system, c) vasculitis phase involved purpura, peripheral neuropathy, and some constitutional symptoms. The key to the treatment of EGPA lies in the early diagnosis of the disease. Early application of glucocorticoids and immunosuppressants can improve symptoms and the overall prognosis of EGPA. Case Description: We presented a case of an 8-year-old boy with a history of short asthma, marked eosinophilia, and multi-organ involvement. The extremely high eosinophil level in the blood (72.50%) prompted the examination of eosinophilic leukemia before EGPA diagnosis was made. Subsequently, this disease was successfully treated. This case report shows a typical case of CSS in childhood because of the extreme eosinophilia. It emphasizes the importance of EGPA is a life-threatening cause of children's eosinophilia. Conclusion: EGPA in children has unique clinical, imaging, and histological characteristics different from those of adults. In pediatric patients, the development and diagnosis of systemic symptoms are often delayed, mainly occurring in the eosinophilic phase, which will lead to specific manifestations. At the same time, we cannot detect a genetic relationship related to EGPA.

Keywords: Churg Strauss syndrome, asthma, vasculitis, hypereosinophilia, eosinophilic granulomatosis polyangiitis

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Authors: C. S. Marques, M. J. Reis Lima, J. Oliveira, E. Teixeira-Lemos

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The growing concerns for physical wellbeing and health have been reflected in the way we choose food in our table. Nowadays, we are all more informed consumers and choose healthier foods. On the other hand, stroke, cancer and atherosclerosis may be somehow minimized by the intake of some bioactive compounds present in food, the so-called nutraceuticals and functional foods. The aim of this work was to make a revision of the published studies about the effects of some bioactive compounds, namely lycopene in human health, in the prevention of diseases, thus playing the role of a functional food. Free radical in human body can induce cell damage and consequently can be responsible for the development of some cancers and chronic diseases. Lycopene is one of the most powerful antioxidants known, being the predominant carotenoid in tomato. The respective chemistry, bioavailability, and its functional role in the prevention of several diseases will be object of this work. On the other hand the inclusion of lycopene in some foods can also be made by biotechnology and represents a way to recover the wastes in the tomato industry with nutritional positive effects in health.

Keywords: tomato, lycopene, bioavailability, functional foods, carotenoids, cancer and antioxidants

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Authors: Hyun-jin Kim, Gumgyung Gu, Dae-Hyun Ko, Woochang Lee, Sail Chun, Won-Ki Min

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Background: Ovarian carcinoma is the fourth most common cause of cancer-related death in women worldwide. HE4, a novel marker for ovarian cancer could be used for monitoring recurrence or progression of disease in patients with invasive epithelial ovarian carcinoma. It is further intended to be used in conjunction with CA 125 to estimate the risk of epithelial ovarian cancer in women presenting with an adnexal mass. In this study, we aim to evaluate the analytical performance and clinical utility of HE4 assay using Architect i 2000SR(Abbott Diagnostics, USA). Methods: The precision was evaluated according to Clinical and Laboratory Standards Institute(CLSI) EP5 guideline. Three levels of control materials were analyzed twice a day in duplicate manner over 20 days. We calculated within run and total coefficient of variation (CV) at each level of control materials. The linearity was evaluated based on CLSI EP6 guideline. Five levels of calibrator were prepared by mixing high and low level of calibrators. For 43 women with adnexal masses, HE4 and CA 125 were measured and Risk of ovarian malignancy (ROMA) scores were calculated. The patients’ medical records were reviewed to determine the clinical utility of HE4 and ROMA score. Results: In a precision study, the within-run and total CV were 2.0 % and 2.3% for low level of control material, 1.9% and 2.4% for medium level and 0.5 % and 1.1% for high level, respectively. The linear range of HE4 was 14.63 to 1475.15pmol/L. Of the 43 patients, two patients in pre-menopausal group showed the ROMA score above the cut-off level (7.3%). One of them showed CA 125 level within the reference range, while the HE4 was higher than the cut-off. Conclusion: The overall analytical performance of HE4 assay using Architect showed high precision and good linearity within clinically important range. HE4 could be an useful marker for managing patients with adnexal masses.

Keywords: HE4, CA125, ROMA, evaluation, performance

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Authors: Mustafa M. Donma, Orkide Donma

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Metabolisms of macrominerals, those of calcium, phosphorus and magnesium, are closely associated with the metabolism of vitamin D. Particularly magnesium, the second most abundant intracellular cation, is related to biochemical and metabolic processes in the body, such as those of carbohydrates, proteins and lipids. The status of each mineral was investigated in obesity to some extent. Their products and ratios may possibly give much more detailed information about the matter. The aim of this study is to investigate possible relations between each macromineral and some obesity-related parameters. This study was performed on 235 children, whose ages were between 06-18 years. Aside from anthropometric measurements, hematological analyses were performed. TANITA body composition monitor using bioelectrical impedance analysis technology was used to establish some obesity-related parameters including basal metabolic rate (BMR), total fat, mineral and muscle masses. World Health Organization body mass index (BMI) percentiles for age and sex were used to constitute the groups. The values above 99^th percentile were defined as morbid obesity. Those between 95^th and 99^th percentiles were included into the obese group. The overweight group comprised of children whose percentiles were between 95 and 85. Children between the 85^th and 15^th percentiles were defined as normal. Metabolic syndrome (MetS) components (waist circumference, fasting blood glucose, triacylglycerol, high density lipoprotein cholesterol, systolic pressure, diastolic pressure) were determined. High performance liquid chromatography was used to determine Vitamin D status by measuring 25-hydroxy cholecalciferol (25-hydroxy vitamin D₃, 25(OH)D). Vitamin D values above 30.0 ng/ml were accepted as sufficient. SPSS statistical package program was used for the evaluation of data. The statistical significance degree was accepted as p < 0.05. The important points were the correlations found between vitamin D and magnesium as well as phosphorus (p < 0.05) that existed in the group with normal BMI values. These correlations were lost in the other groups. The ratio of phosphorus to magnesium was even much more highly correlated with vitamin D (p < 0.001). The negative correlation between magnesium and total fat mass (p < 0.01) was confined to the MetS group showing the inverse relationship between magnesium levels and obesity degree. In this group, calcium*magnesium product exhibited the highest correlation with total fat mass (p < 0.001) among all groups. Only in the MetS group was a negative correlation found between BMR and calcium*magnesium product (p < 0.05). In conclusion, magnesium is located at the center of attraction concerning its relationships with vitamin D, fat mass and MetS. The ratios and products derived from macrominerals including magnesium have pointed out stronger associations other than each element alone. Final considerations have shown that unique correlations of magnesium as well as calcium*magnesium product with total fat mass have drawn attention particularly in the MetS group, possibly due to the derangements in some basic elements of carbohydrate as well as lipid metabolism.

Keywords: macrominerals, metabolic syndrome, pediatric obesity, vitamin D

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Authors: Damião Sousa, Hasan Turkez, Ozlem Tozlu, Tamires Lima

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Glioblastoma (GBM) is an aggressive cancer from the brain and with high prevalence and significant morbimortality. Therefore, it is necessary to investigate new therapeutic options against this pathology. Thus, the purpose of this study was to evaluate the antitumor activity from Mentha crispa essential oil (MCEO), its major constituent rotundifolone (ROT) and a series of six analogues on human U87MG glioblastoma cell line. The antitumor effects of the compounds on human U87MG-GBM cell line were assessed using in vitro cell viability assays. In addition, biosafety tests were performed on cultured human blood cells. The data show that MCEO, 1,2-perillaldehyde epoxide (EPER1) and perillaldehyde (PALD) were the most cytotoxic compounds against the U87MG cells, with IC50 values of 16.263, 15.087 and 14.888 μg/mL, respectively. The treatment with MCEO, EPER1 and PALD did not lead to damage in blood cells. These chemical analogues may be useful as prototypes for development of novel antitumor drugs due to their promising activities and toxicological safety.

Keywords: antitumor activity, cancer, natural products, terpenes

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Authors: Courtney Manthey-Pierce, Anna Warrener

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Polycystic ovarian syndrome (PCOS) is the most common endocrine disruptive disorder in females. PCOS is primarily characterized by polycystic ovaries, anovulation, hirsutism, insulin resistance, and hyperandrogenism. Despite negative reproductive consequences for females from anovulation and endocrine dysfunction, genes associated with the pathogenesis of PCOS are highly hereditable (h2 = 0.72). An evolutionary mismatch occurs when a trait that evolved in one environment has become maladaptive in another environment. The idea that PCOS is an evolutionary mismatch disease has been promoted by several researchers. Each trait of the resulting PCOS phenotype should be investigated individually in order to demonstrate an evolutionary mismatch. Hyperandrogenism is often regarded as the main characteristic of PCOS Hyperandrogenism may have aided with conception in older females, increased bone mineral density, and supported prolonged breastfeeding in nutritionally distressed populations. Because of the high prevalence of PCOS in the modern world, approximately 6%, it is often argued that PCOS emerged in an ancestral population prior to the migration out of Africa approximately 200,000 years ago. This environment would be characterized by sporadic periods of nutrition deficit and resource hardships as the climate began changing. Presently, modern society is characterized by obesity and sedentary lifestyles. The prevalence of obesity renders hyperandrogenism PCOS useless as there are no periods of nutritional distress requiring androgens for increased reproductive rates. In an ancestral environment, hyperandrogenism would likely lead to sporadic anovulation and mild secondary symptoms, however high levels of androgens in a modern environment led to prolonged if not permanent infertility and excessive secondary problems. Thus, hyperandrogenism related to PCOS appears to meet evolutionary mismatch criteria. Seen in this light, PCOS may be effectively treated as a probably evolutionary mismatch.

Keywords: evolutionary mismatch, heritability, hyperandrogenism, mismatch disorder

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Authors: Kabange Kasumbwe, Viresh Mohanlall, Bharti Odhav, Venu Narayanaswamy

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Coumarins are naturally occurring plant metabolites known for their pharmacological properties such as anticoagulant, antimicrobial, anticancer, antioxidant, anti-inflammatory and antiviral properties. The pharmacological and biochemical properties and curative applications of coumarins depend on the substitution around the coumarin core structure. In the present study, seven halogenated coumarins CMRN1-CMRN7 were synthesized and evaluated for their anticancer activity. The cytotoxicity potential of the test compounds was evaluated against UACC62 (Melanoma), MCF-7 (Breast cancer) and PBM (Peripheral Blood Mononuclear) cell lines using MTT assay keeping doxorubicin as standard drug. The apoptotic potential of the coumarin compounds was evaluated against UACC62 (Melanoma) cell by assessing their morphological changes, membrane change, mitochondria membrane potential; pro-apoptotic changes were investigated using the AnnexinV-PI staining, JC-1, caspase-3 enzyme kits respectively on flow cytometer. The synthetic coumarin has strongly suppressed the cell proliferation of UACC-62 (Melanoma) and MCF-7 (Breast) Cancer cells, the higher toxicity of these compounds against UACC-62 (Melanoma) and MCF-7 (Breast) were CMRN3, CMRN4, CMRN5, CMRN6. However, compounds CMRN1, CMRN2, and CMRN7 had no significant inhibitory effect. Furthermore the active compounds CMRN3, CMRN4, CMRN5, CMRN6 exerted antiproliferative effects through apoptosis induction against UACC-62 (Melanoma), suggesting their potential could be considered as attractive lead molecules in the future for the development of potential anticancer agents since one of the important criteria in the development of therapeutic drugs for cancer treatment is to have high selectivity and less or no side-effects on normal cells and these compounds had no inhibitory effect against the PBMC cells.

Keywords: coumarin, MTT, apoptosis, cytotoxicity

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Authors: Nima Samie, Sekaran Muniandy, Zahurin Mohamed, M. S. Kanthimathi

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Although number of indole containing compounds have been reported to have anticancer properties in vitro but only a few of them show potential as anticancer compounds in vivo. The current study was to evaluate the mechanism of cytotoxicity of selected indolic compound in vivo and in vitro. In this context, we determined the potency of the compound in the induction of apoptosis, cell cycle arrest, and cytoskeleton rearrangement. HT-29, WiDr, CCD-18Co, human monocyte/macrophage CRL-9855, and B lymphocyte CCL-156 cell lines were used to determine the IC50 of the compound using the MTT assay. Analysis of apoptosis was carried out using immunofluorescence, acridine orange/ propidium iodide double staining, Annexin-V-FITC assay, evaluation of the translocation of NF-kB, oxygen radical antioxidant capacity, quenching of reactive oxygen species content, measurement of LDH release, caspase-3/-7, -8 and -9 assays and western blotting. The cell cycle arrest was examined using flowcytometry and gene expression was assessed using qPCR array. Results displayed a potent suppressive effect on HT-29 and WiDr after 24 h of treatment with IC50 value of 2.52±0.34 µg/ml and 2.13±0.65 µg/ml respectively. This cytotoxic effect on normal, monocyte/macrophage and B-cells was insignificant. Dipping in the mitochondrial membrane potential and increased release of cytochrome c from the mitochondria indicated induction of the intrinsic apoptosis pathway by the compound. Activation of this pathway was further evidenced by significant activation of caspase-9 and 3/7. The compound was also shown to activate the extrinsic pathways of apoptosis via activation of caspase-8 which is linked to the suppression of NF-kB translocation to the nucleus. Cell cycle arrest in the G1 phase and up-regulation of glutathione reductase, based on excessive ROS production were also observed. These findings were further investigated for inhibitory efficiency of the compound on colonic aberrant crypt foci in male rats. Rats were divided in to 5 groups: vehicle, cancer control, positive control groups and the groups treated with 25 and 50 mg/kg of compounds for 10 weeks. Administration of compound suppressed total colonic ACF formation up to 73.4%. The results also showed that treatment with the compound significantly reduced the level of malondialdehyde while increasing superoxide dismutase and catalase activities. Furthermore, the down-regulation of PCNA and Bcl2 and the up-regulation of Bax was confirmed by immunohistochemical staining. The outcome of this study suggest sthat the indolic compound is a potent anti-cancer agent against colon cancer and can be further evaluated by animal trial.

Keywords: indolic compound, chemoprevention, crypt, azoxymethane, colon cancer

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Authors: Soheil Zorofchian Moghadamtousi, Habsah Abdul Kadir, Mohammadjavad Paydar, Elham Rouhollahi, Hamed Karimian

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The present study was designed to evaluate the molecular mechanisms of Annona muricata leaves ethyl acetate extract (AMEAE) against lung cancer A549 cells. Cell viability analysis revealed the selective cytotoxic effect of AMEAE towards A549 cells. Treatment of A549 cells with AMEAE significantly elevated the reactive oxygen species formation, followed by attenuation of mitochondrial membrane potential via upregulation of Bax and downregulation of Bcl-2, accompanied by cytochrome c release to the cytosol. The released cytochrome c triggered the activation of caspase-9 followed by caspase-3. In addition, AMEAE-induced apoptosis was accompanied by cell cycle arrest at G1 phase. Our data showed for the first time that AMEAE inhibited the proliferation of A549 cells, leading to cell cycle arrest and programmed cell death through activation of the mitochondrial-mediated signaling pathway.

Keywords: Annona muricata, lung cancer, apoptosis, mitochondria

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