Vitamin D Reduces the Activity of Adenosine Deaminase and Oxidative Stress in Patients with Type Two Diabetes Mellitus.

SCOPE: Patients with Type 2 diabetes mellitus (T2DM) have lower levels of vitamin D. An elevation in uric acid (UA) contributes to T2DM via an increase in oxidative stress. Adenosine deaminase (ADA) is an enzyme of the purine degradation pathway. It is hypothesized that a reduction of ADA activity via vitamin D supplementation reduces UA and oxidative stress. METHODS AND RESULTS: A total of 162 participants (81 with T2DM and 81 controls) are enrolled in a case-control study. A follow-up interventional study is performed on 30 patients with vitamin D deficiency. These patients receive 50 000 IU (international units) of vitamin D3 on a weekly basis for 12 weeks. This intervention is followed by the measurement of several markers. T2DM patients has higher ADA activity, UA, and lipid peroxidation but lower 25-hydroxy-vitamin D (25 (OH) vitamin D) and GSH/GSSG ratio (p < 0.05). Vitamin D supplementation results in a reduction of ADA activity and UA levels (p < 0.05) along with an increase in GSH/GSSG ratio (p < 0.05). CONCLUSION: The results highlight the presence of an axis in T2DM patients between ADA, UA, and oxidative stress. Modulation of this axis can be achieved by clinically approved vitamin D supplementation protocols.

Label-free quantitative proteomics analysis for type 2 diabetes mellitus early diagnostic marker discovery using data-independent acquisition mass spectrometry (DIA-MS).

Type-2 diabetes mellitus (T2DM) therapy requires early diagnosis and complication avoidance. Unfortunately, current diagnostic markers do not meet these needs. Data-independent acquisition mass spectrometry (DIA-MS) offers a solution for clinical diagnosis, providing reliable and precise sample quantification. This study utilized DIA-MS to investigate proteomic differential expression in the serum of recently diagnosed T2DM patients. The study conducted a comparative protein expression analysis between healthy and recently diagnosed T2DM groups (discovery cohort). A candidate protein was then validated using enzyme-linked immune assay (ELISA) on serum samples collected from T2DM patients (n = 87) and healthy control (n = 60) (validation cohort). A total of 1074 proteins were identified, and 90 were significantly dysregulated between the two groups, including 32 newly associated with T2DM. Among these proteins, the expression of S100 calcium-binding protein A6 (S100A6) was validated by ELISA. It showed a significant increase in T2DM samples compared to the control group. It was evaluated as a biomarker using the receiver operating characteristic (ROC) curve, consistent with the DIA-MS results. Novel proteins are reported to be involved in the development and progression of T2DM. Further studies are required to investigate the differential expression of candidate marker proteins in a larger population of T2DM patients.

Disparities in Obstetric, Neonatal, and Birth Outcomes Among Syrian Women Refugees and Jordanian Women.

Objectives: To compare obstetric and neonatal characteristics and birth outcomes between Syrian refugees and native women in Jordan. Methods: We used the Jordan Stillbirths and Neonatal Deaths Surveillance System to extract sociodemographic and obstetric characteristics of the mothers and birth characteristics of newborns. Multivariate analysis was used to compare the characteristics of 26,139 Jordanian women (27,468 births) and 3,453 Syrian women refugees (3,638 births) who gave birth in five referral hospitals (May 2019 and December 2020). Results: The proportions of low birthweight (14.1% vs. 11.8%, p < 0.001) and small for gestational age (12.0% vs. 10.0%, p < 0.001) newborns were significantly higher for those born to Syrian women compared to those born to Jordanian women. The stillbirth rate (15.1 vs. 9.9 per 1,000 births, p = 0.003), the neonatal death rate (21.2 vs. 13.2 per 1,000 live births, p < 0.001), and perinatal death rate (21.2 vs. 13.2 per 1,000 births, p < 0.001) were significantly higher for the Syrian births. After adjusting for sociodemographic and obstetric characteristics of women, only perinatal death was statistically significantly higher among Syrian babies compared to Jordanian babies (OR = 1.3, 95% CI: 1.1-1.7, p = 0.035). Conclusion: Syrian refugee mothers had a significantly higher risk of adverse obstetric and neonatal outcomes including higher rate of perinatal death compared to Jordanian women.

Serum Leptin Receptor and the rs1137101 Variant of the LEPR Gene Are Associated with Bladder Cancer.

Globally, bladder cancer (BC) is one of the ten most common tumors. Obesity is a worldwide problem associated with an increased BC risk. Considering that levels of leptin and/or its receptor are often deregulated in obese individuals, we hypothesized that they could contribute to BC. To test this hypothesis, we utilized a case-control study in which 116 patients with a confirmed diagnosis of BC and 116 controls were recruited. The serum levels of leptin and leptin receptor were measured. Patients and controls were also genotyped for SNPs in the LEP (rs7799039, rs791620, and rs2167270) and LEPR genes (rs1137100, rs1137101, and rs1805094). The univariate analysis indicated that BC patients had significantly higher levels of leptin and lower levels of leptin receptor (p < 0.05). Moreover, rs7799039 of LEP and rs1137101 of LEPR were associated with BC (p < 0.05). In the multivariate analysis, leptin receptor levels were protective (OR: 0.98, 95% CI = 0.97-0.99, p = 0.002) while the GG genotype of rs1137101 of LEPR increased BC risk (OR: 3.42, 95% CI = 1.27-9.20, p = 0.02). These findings highlight that lifestyle changes could be useful in preventing BC and that disturbances in energy metabolism could play a role in the pathobiology of BC.

Discovery of a novel genetic variant in the N-acetyltransferase2 (NAT2) gene that is associated with bladder cancer risk.

Smoking is a main risk factor for bladder cancer (BC). NAT2 is a drug-metabolizing enzyme that catalyses the detoxification of many xenobiotics and carcinogens. Single nucleotide polymorphism (SNP) in NAT2 results in different acetylation phenotypes (fast, intermediate or slow). Certain NAT2 SNPs were associated with BC and/or modified the association of BC with smoking. However, limited evidence is available among BC patients or smokers from Jordan. This study aimed to discover novel SNPs in NAT2 and to assess the association with BC. This was a case-control study among 120 BC patients and 120 controls. Amplification of a 446 bp fragment of NAT2 encoding the N-catalytic domain was conducted using a polymerase chain reaction. Gene sequencing was done using Sanger-based technology. A total of 40 SNPs were detected. Two variants were significantly associated with BC (p<0.05); namely a novel c.87G>A and the reported c.341T>C. Regarding c.87G>A, genotype distribution was significantly associated with BC and subgroup analysis confirmed that this was significant in both smokers (p=0.007) and non-smokers (p=0.001). Regression subgroup analysis suggested GA as a risk factor among smokers (AOR= 2.356). The frequencies of TC and CC genotypes of c.341T>C were significantly higher in BC (p<0.05). This was statistically significant among smokers only (p=0.044), upon subgroup analysis. Multivariate analysis showed that subjects with TC genotype are 6.15 more likely to develop BC and regression subgroup analysis revealed TC as a risk factor among smokers (AOR=5.47). This is the first study from Jordan to report the association of smoking and two NAT2 variants with BC. The data supports the use of GA and TC genotypes of the novel c.87G>A and the reported c.341T>C SNPs, respectively as potential biomarkers of BC, particularly among smokers. Future investigations with a larger population are required to support our findings.

Identifying psychosocial problems, needs, and coping mechanisms of adolescent Syrian refugees in Jordan.

Background: Refugees who have fled war zones are at a heightened risk of psychosocial problems that can impact their ability to function in day-to-day life and place a significant burden on the family structure. This study aimed to assess the psychosocial problems and needs and coping mechanisms of Adolescent Syrian refugees in Jordan. Methods: Between October and December 2018, we conducted a qualitative study using semi-structured interviews with a sample of key and individual informants. Our sample included 20 primary healthcare professionals, 20 schoolteachers, 20 Syrian parents, and 20 adolescents aged 12-17 years. All interviews were transcribed verbatim, and we utilized thematic analysis to group, categorize, and analyze the original Arabic language transcripts. To ensure thorough analysis, we adopted a bottom-up inductive approach that covered the six-phase iterative process proposed by Braun and Clarke. Results: The main psychosocial problems encountered by Syrian adolescents included stress, depression, loneliness, lack of a sense of security, isolation, aggressiveness, fear of war, and family disintegration. Almost all schoolteachers reported that they observed that Jordanian adolescents are more settled, self-confident, and financially stable relative to their Syrian peers. The Jordanian government and community were praised for their support, including education, recreational centers, health services, and awareness campaigns. Going to school, praying and reading the Holy Quran, listening to music, and talking to friends and engaging with them were reported as the main coping mechanisms. The majority of respondents said that more services are still needed for adolescents, including more places for entertainment, psychosocial support and psychological counseling, medical care, job creation, and providing health insurance. Conclusion: Syrian refugees are aware of the psychological aspects of their situation, but they are not always able to access clinic-based humanitarian assistance for mental health and psychosocial support. Stakeholders must interact with refugees to learn about their needs and develop services that are appropriate for their culture.

The attitude and knowledge of pediatricians and family physicians toward COVID-19 vaccination in children: A cross-sectional study.

COVID-19 vaccines to children are expected to reduce the transmission of the disease to high-risk groups and achieve herd immunity in younger populations. A positive attitude toward COVID-19 vaccination in children among healthcare workers (HCWs) is predicted to reduce parents' hesitancy to vaccinate their children. This study aimed to assess the knowledge and attitude of pediatricians and family physicians toward COVID-19 vaccination in children. A total of 112 pediatricians and 96 family physicians (specialists and residents) were interviewed to assess the level of knowledge, attitude, and perceived safety of COVID-19 vaccines for children. Physicians willing to receive regular COVID-19 vaccination (analogous to the influenza vaccine) had significantly higher knowledge and attitude scores (P < .05). Multivariate analysis indicated that a higher knowledge score and having at least five years of experience as a specialist were significantly associated with a positive attitude among pediatricians or family physicians (P < .05). Pfizer/BioNTech was the preferred COVID-19 vaccine in children among physicians of both groups (>67%). Around 71% of physicians believed COVID-19 vaccines for children do not cause or worsen any health condition. Educational and training programs that increase the knowledge of physicians about COVID-19 vaccines and their safety in children are recommended to inform a more positive attitude.

Leptin and the rs2167270 Polymorphism Are Associated with Glycemic Control in Type Two Diabetes Mellitus Patients on Metformin Therapy.

Background and Objectives: Type two diabetes mellitus (T2DM) is a chronic disease with debilitating complications and high mortality. Evidence indicates that good glycemic control delays disease progression and is hence a target of disease management protocols. Nonetheless, some patients cannot maintain glycemic control. This study aimed to investigate the association between serum leptin levels and several SNPs of the LEP gene with the lack of glycemic control in T2DM patients on metformin therapy. Materials and Methods: In a hospital-based case-control study, 170 patients with poor glycemic control and 170 patients with good glycemic control were recruited. Serum leptin was measured. Patients were genotyped for three SNPs in the LEP gene (rs7799039, rs2167270, and rs791620). Results: Serum leptin was significantly lower in T2DM patients with poor glycemic control (p < 0.05). In multivariate analysis, serum leptin levels significantly lowered the risk of having poor glycemic control (OR = 0.985; CI: 0.976-0.994; p = 0.002); moreover, the GA genotype of rs2167270 was protective against poor glycemic control compared to the GG genotype (OR = 0.417; CI: 0.245-0.712; p = 0.001). Conclusions: Higher serum leptin and the GA genotype of the rs2167270 SNP of the LEP gene were associated with good glycemic control in T2DM patients on metformin therapy. Further studies with a larger sample size from multiple institutions are required to validate the findings.

Factors Associated With University Students' Attitude Toward Euthanasia.

Although euthanasia has been practiced for thousands of years, a wide controversy still exists around it. This study aimed to assess the attitude of university students toward euthanasia and its associated factors. The study included an online self-administered survey. Survey questions consisted of demographic information, psychological condition, and attitude toward euthanasia. A total of 1,188 students participated in the study. Approximately only one-third of the respondents (34.1%) viewed euthanasia as a moral practice, and just one-quarter (25.3%) supported legalizing it. The main reason for not supporting euthanasia was religious considerations (72.2%), followed by moral considerations (46.5%). Factors that predicted a positive attitude toward euthanasia (p < .05) included undefined religion, being male, feeling lonely, or having suicidal thoughts. Conclusively, the negative attitude toward euthanasia is primarily driven by religious beliefs. Furthermore, gender and psychological status play critical roles in students' attitudes toward euthanasia.

Association of vitamin D levels and polymorphisms in vitamin D receptor with type 2 diabetes mellitus.

Type 2 diabetes mellitus (T2DM) is a leading cause of death. The prevalence of T2DM in countries of the Middle East and North Africa (MENA) region, including Jordan, is among the highest worldwide. The reason(s) behind the epidemic nature of T2DM in Jordan are unknown but warrant further exploration. Studies have indicated that T2DM could be influenced by diet and/or genetic background. Evidence suggests that numerous patients with T2DM are deficient in vitamin D. The activity of vitamin D on its target tissues may be influenced by single nucleotide polymorphisms (SNPs) in the vitamin D receptor (VDR) gene. It was therefore hypothesized that SNPs in VDR could modify the risk of T2DM. To test this hypothesis, 125 patients with T2DM were recruited along with 125 controls. The study subjects were genotyped for variations in rs2228570, rs1544410, rs7975232, and rs731236 SNPs in the VDR. The levels of 25-hydroxyvitamin D [25(OH)D] were measured from the serum. The analysis revealed that reduced 25(OH)D and age were associated with the risk of T2DM (P<0.05). Moreover, under a dominant inheritance model, the GG genotype of rs2228570 was revealed to increase the risk of T2DM in univariate and multivariate analysis (P<0.05). Additionally, a chromosomal block containing the GAAG haplotype of VDR SNPs increased the risk of T2DM (OR=1.909; CI: 1.260-2.891; P=0.0021). Collectively, the present study revealed that low levels of serum 25(OH)D and rs2228570 of the VDR gene are associated with the risk of T2DM.

Genetic variation in the ADIPOQ gene and serum adiponectin increase the risk of bladder cancer.

Bladder cancer (BC) is the 10th most common cancer worldwide. Genetic studies estimated 30% heritability in BC risk. Adiponectin is an adipocytokine that has important roles in the regulation of energy metabolism. Recent evidence suggests dysregulation of adiponectin levels in BC tissues. Serum level of adiponectin is influenced by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. However, limited evidence is available regarding the association between adiponectin serum levels or SNPs in ADIPOQ and BC risk. This study aimed to assess whether adiponectin serum levels or SNPs in ADIPOQ may modify BC risk. In this case-control study, 114 BC patients were recruited along with 114 controls. Study subjects were genotyped for variations in ADIPOQ SNPs, namely rs17300539, rs266729, rs2241766, and rs1501299. Adiponectin levels were measured from the serum of study subjects. Our analysis showed that the G allele and the GG genotype of rs1501299 were significantly more frequent in BC patients compared to those in the control group (p-value < 0.05). Moreover, two ADIPOQ haplotypes containing the above G allele were associated with increased BC risk (p-value < 0.05). Multivariate analysis showed that increased serum adiponectin, smoking or age were all significant predictors of BC (p-value < 0.05). The data supports use of serum adiponectin and the G allele of rs1501299 SNP in ADIPOQ as potential biomarkers and/or targets in BC. To further validate findings in this study, larger populations of various ethnicities and/or genetic backgrounds are required. More investigations on the functional role of adiponectin in BC will also provide better understanding of potential targeting adiponectin for BC treatment.

Normalization of Vitamin D Serum Levels in Patients with Type Two Diabetes Mellitus Reduces Levels of Branched Chain Amino Acids.

Background and Objectives: Vitamin D is involved in pancreatic beta-cell function, insulin sensitivity, and inflammation. Further, elevation in branched-chain amino acids (BCAAs) has been implicated in type 2 diabetes (T2DM) pathology. However, the relationship between vitamin D and BCAAs in T2DM remains unclear. The current study aimed to investigate the relationship between vitamin D and BCAAs in T2DM. Materials and Methods: In total, 230 participants (137 with T2DM and 93 healthy controls) were recruited in a cross-sectional study. Furthermore, an additional follow-up study was performed, including 20 T2DM patients with vitamin D deficiency. These patients were prescribed weekly vitamin D tablets (50,000 IU) for three months. The levels of several biochemical parameters were examined at the end of the vitamin D supplementation. Results: The results showed that patients with T2DM had higher serum levels of BCAAs and lower serum levels of 25-hydroxyvitamin D (25(OH)D) compared with those of the healthy controls (p < 0.01). The serum levels of vitamin D were negatively correlated with BCAA levels in T2DM patients (r = −0.1731, p < 0.05). In the follow-up study, 25(OH)D levels were significantly improved (p < 0.001) following vitamin D supplementation. Vitamin D supplementation significantly reduced the levels of BCAAs, HbA1c, total cholesterol, triglycerides, and fasting glucose (p < 0.01). Conclusion: Overall, these results suggest a role for BCAAs and vitamin D in the etiology and progression of T2DM. Thus, managing vitamin D deficiency in patients with T2DM may improve glycemic control and lower BCAA levels.

Correlation between vitamin D and serum brain derived neurotropic factor levels in type 2 diabetes mellitus patients.

Diabetes Mellitus (DM) currently ranks as the most common endocrine disorder worldwide. Current opinion views DM as a group of heterogeneous metabolic diseases characterized by hyperglycemia triggered by defects in the ability of the body to produce or use insulin in type 1 and 2 DM, respectively. Brain-derived neurotrophic factor (BDNF), one of the neurotrophin family of growth factors, has been linked to the pathogenesis of DM and insulin resistance. Moreover, vitamin D has been associated with insulin resistance and DM. Recently, the interactions between vitamin D and BDNF have been investigated in diabetic rats. However, this correlation has never been investigated in humans. Thus, the aim of the present study was to assess the alterations in serum BDNF and vitamin D levels in T2DM patients in Jordan, prior to and following vitamin D supplementation. A combination of non-experimental case-control and experimental designed studies were utilized to assess the relationship between serum BDNF and vitamin D levels in T2DM patients. The levels of BDNF and vitamin D were measured using commercially available ELISA kits, and fasting blood glucose (FBG) and HbA1c levels were measured in medical labs. The results showed that diabetic patients had lower levels of serum vitamin D and higher levels of BDNF compared with the healthy controls. Moreover, linear regression analysis indicated that BDNF levels were inversely correlated with serum vitamin D levels. Furthermore, vitamin D supplementation significantly increased vitamin D serum levels and decreased BDNF serum levels in diabetic patients. Intriguingly, FBG and HbA1c levels were significantly improved post vitamin D supplementation. These data demonstrate a positive effect of vitamin D supplementation in diabetic patients suggesting the implementation of vitamin D as part of future T2DM treatment plans. However, additional studies are needed to investigate the direct link between vitamin D, BDNF, and T2DM.

Single Nucleotide Polymorphism in the ADIPOQ Gene Modifies Adiponectin Levels and Glycemic Control in Type Two Diabetes Mellitus Patients.

Diabetes mellitus (DM) is the ninth leading cause of death worldwide. Mortality from DM is largely attributed to disease complications. Glycemic control of DM patients reduces mortality. Studies indicated that the lack of glycemic control in DM patients could be influenced by the genetic background of the patients. Evidence suggests that adiponectin levels are dysregulated in DM patients with poor glycemic control. Serum adiponectin level is a heritable trait influenced by single nucleotide polymorphisms (SNPs) in the ADIPOQ gene. It is hypothesized that SNPs in ADIPOQ could modify glycemic control in DM patients. To test this hypothesis, 375 type 2 DM (T2DM) patients were recruited. Patients were classified into good vs. poor glycemic control according to hemoglobin A1c levels. Study subjects were genotyped for variations of four SNPs in ADIPOQ (rs17300539, rs266729, rs2241766, and rs1501299). Adiponectin levels were measured from the serum. Our analysis showed that reduced serum adiponectin, a longer duration of treatment, and increased insulin resistance were all significant predictors of poor glycemic control. Moreover, the T allele and the TT genotype of rs2241766 were significantly more frequent in patients with poor glycemic control (P < 0.05). Individuals with the TT genotype of rs2241766 had significantly lower levels of serum adiponectin (P < 0.05). It was concluded that lower levels of serum adiponectin and the T allele of rs2241766 SNP in ADIPOQ were associated with poor glycemic control in T2DM patients.

Soft Tissue Sarcomas: A 16-Year Experience of a Tertiary Referral Hospital in North Jordan.

Background and Objectives: Sarcomas are rare malignant tumors of mesenchymal origin. Their low prevalence and histological heterogeneity make their diagnosis a challenging task. To the best of our knowledge, the epidemiology of soft tissue sarcomas (STSs) was not well studied in Jordan. This study thus aimed to determine STS epidemiologic trends at King Abdullah University Hospital (KAUH); a tertiary hospital that provides cancer healthcare for 70% of the population in Irbid Governorate, North Jordan. The findings of this study will provide a good reference point of the burden of STSs in Jordan and the Middle East region. Materials and Methods: All cases with confirmed STS diagnoses who attended KAUH from January 2003 until December 2018 were included in the initial analysis. Bone sarcomas, gastrointestinal stromal tumors and uterine sarcomas were not included in the study. Information collected from the pathology reports and electronic medical records was used to determine STS prevalence, incidence rate, age and gender distributions, histological types and anatomic location. Cases were reviewed by three pathologists with interest in soft tissue tumors. The findings were compared with literature. Results: In total, 157 STS cases were reported (1.9% of cancers diagnosed at KAUH during the 16-year study period). Crude annual incidence rate (IR) per 100,000 person-years ranged from 0.48 in 2015 to 1.83 in 2011 (average = 1.04). Age-standardized IR (ASR)(World WHO 2000-2025) was 1.37. Male:female ratio was 1.3:1. Median age was 39 years. Age ranged from <1 year to 90 years. Overall STS rates increased with age. The most common histological types were liposarcoma (19%), rhabdomyosarcoma (17%) and leiomyosarcoma (10%). The most common anatomic location was the extremity (40.1%), followed by the trunk (14.7%), then head and neck (10.8%). Conclusion: STSs are rare in North Jordan. A slight increase in their incidence was identified during the study period similar to global trends. The collection of relevant data on established risk factors along with a broader scale evaluation of the epidemiology of STS in the Middle East region is recommended to better evaluate disease burden and trends.

The Benefits of Mindfulness Meditation on Trait Mindfulness, Perceived Stress, Cortisol, and C-Reactive Protein in Nursing Students: A Randomized Controlled Trial.

PURPOSE: Mindfulness meditation was used to reduce stress and its responses such as cortisol and C-reactive protein (CRP) among healthy and ill individuals in various cultures, but its effect has not yet been studied among nursing students, experiencing tremendous stress. The objective of this study was to examine the effects of mindfulness meditation on trait mindfulness, perceived stress, serum cortisol, and serum C-reactive proteins (CRP) in nursing students. PATIENTS AND METHODS: Using a two-arm, randomized, parallel study (conducted in a large university in Jordan, 108 nursing students were randomly assigned to experimental group receiving five 30-minute weekly sessions of mindfulness meditation and control group sitting quiet during the experimental sessions. Trait mindfulness, perceived stress, serum cortisol, and CRP were measured at baseline and end of the intervention. RESULTS: Using one-way MANOVA and post-hoc comparisons, the results showed that mindfulness meditation was significantly effective in decreasing serum cortisol levels and perceived stress. The mindfulness meditation also decreased CRP and increased trait mindfulness although the results did not reach statistically significant levels. CONCLUSION: These findings underscore the need for serious consideration of mindfulness meditation in nursing colleges to improve stress and raise immunity in this vulnerable population. TRIAL REGISTRATION: Mindfulness Meditation for Nursing Students: clinicaltrials.gov, identifier: NCT05099224.

Mechanism of Oxytocin-Induced Contraction in Rat Gastric Circular Smooth Muscle.

Oxytocin produces an excitatory effect on gastric muscle through the activation of receptors present on stomach smooth muscle cells. However, the intracellular mechanisms that mediate oxytocin excitatory effects are still largely unknown. Therefore, we aimed to investigate the signaling pathways involved in oxytocin-induced contractions in gastric smooth muscle, shedding light on phospholipase C (PLC)-ß1 signaling and its downstream molecules, including inositol 1,4,5- trisphosphate (IP3) and myosin light chain kinase (MLCK). The contractions of gastric smooth muscle from male rats were measured in an organ bath set up in response to exogenous oxytocin 10-7 M, in the presence and absence of inhibitors of the indicated signaling molecules. Oxytocin (10-9-10-5 M) induced dose-dependent stomach smooth muscle contraction. Pre-incubation with atosiban, an oxytocin receptor inhibitor, abolished the oxytocin-induced contraction. Moreover, PLC ß1 inhibitor (U73122) and IP3 inhibitor Xestospongin C inhibited oxytocin-induced muscle contraction to various degrees. Verapamil, a calcium channel blocker, inhibited oxytocin-induced contraction, and pre-incubation of the strips, with both verapamil and Xestospongin C, further inhibited the excitatory effect of oxytocin. Chelation of intracellular calcium with BAPT-AM (1,2-bis-(o-aminophenoxy) ethane-N,N,N',N'-tetraacetic acid) significantly inhibited the effect of oxytocin on muscle contraction. Finally, pre-incubation of the strips with the Ca2+/calmodulin-dependent protein kinase selective inhibitor STO-609 significantly inhibited the contraction induced by oxytocin. These results suggest that oxytocin directly stimulates its cell surface receptor to activate PLC ß1, which in turn liberates IP3, which eventually elevates intracellular calcium, the prerequisite for smooth muscle contraction.

The Protective Effects of Pioglitazone Against Cognitive Impairment Caused by L-methionine Administration in a Rat Model.

PURPOSE: Accumulating evidence indicates that elevated levels of methionine are associated with cognitive decline, including loss of memory. The exact mechanisms behind this observation are not completely understood but could be related to an increase in oxidative stress markers in hippocampal tissues. The above increase in oxidative stress could be directly caused by an increase in the blood levels of methionine (hypermethioninemia) or one of its metabolites, such as homocysteine. Pioglitazone is a drug primarily used for the treatment of type 2 diabetes mellitus. Several reports showed that using pioglitazone protects against cognitive decline observed in Alzheimer's disease. Pioglitazone has antioxidant properties independent of its hypoglycemic effects. Taken together, we hypothesized that pioglitazone protects against memory loss triggered by elevated levels of methionine through lowering oxidative stress in the hippocampus. METHODS: To test this hypothesis, we used chronic administration of L-methionine in a rat model. Spatial learning and memory were evaluated in the model using a radial arm water maze (RAWM). The levels of several markers related to oxidative stress were measured in hippocampal tissues recovered from experimental rats. RESULTS: Current results showed that administration of L-methionine was associated with a significant loss of short- and long-term memory and an increase in blood homocysteine levels. The above memory changes were associated with an increase in lipid peroxidation and a decrease in the activity of catalase and glutathione peroxidase antioxidant enzymes in the hippocampus. The combined treatment of pioglitazone with L-methionine protected rat model from memory loss. It also prevented changes observed in lipid peroxidation and changes in the activity of catalase and glutathione peroxidase enzymes. CONCLUSION: Current findings indicate that pioglitazone is a viable therapeutic option that protects against cognitive changes observed upon administration of L-methionine.

Mutational Analysis of EZH2 Gene in Patients with Colorectal Adenoma Reveals a Genetic Variant Associated with Risk of Malignant Transformation.

BACKGROUND: Several studies have revealed that chromatin modifications lead to activation or repression of multiple genes including oncogenes and tumor suppressor genes. Inactivation mutation in EZH2 gene would result in activation of oncogenes. The aim of this case-control study was to identify mutations in the EZH2 gene, to study their prevalence among Jordanian patients with colorectal adenoma and to determine how these mutations could be related to colorectal cancer (CRC) progression. METHODS: EZH2 gene sequencing was done by Sanger method for 100 DNA samples, extracted from blood of 50 patients, and 50 controls. Sequencing results were analyzed by Chromaspro and mutational effects were predicted by Mutation Taster bioinformatics tool. RESULTS: Four variants were identified in Jordanian patients with adenoma; Two novel variantsc.1941T>A and c.2201G>C and two reported variants, g.73038C>T and g.75508A>C. g.73038C>T is the most common germline variant identified in this study. A significant association between the presence of c.2201G>C mutation and colorectal adenoma was found (p value < 0.05). CONCLUSION: The present study identified several variants in EZH2 gene among Jordanians with colorectal adenoma.

A single nucleotide polymorphism in BCAT1 gene is associated with type 2 diabetes mellitus.

The level of circulatory branched chain amino acids (BCAAs) is often increased in type 2 diabetes mellitus (T2DM). Catabolism of BCAAs involves a transamination reaction mediated by the branched chain amino acid aminotransferase (BCAT1) enzyme. Differences in the level of BCAT1 were found to be linked with hypertension, obesity, and cancer. Herein, using a case control design, we tested the association of rs9668920 and rs12321766 polymorphisms in BCAT1 gene with T2DM. Three hundred subjects were recruited in the study. Genotyping of the indicated polymorphisms was achieved using restriction fragment length polymorphism technique after amplification of the target sequences. The results showed that, under a recessive inheritance model, the GG genotype of rs9668920 increased the risk of T2DM (P=0.026; OR 2.60; 95% CI 1.119-6.048). This effect was independent of the age, body mass index, waist circumference, serum glucose, cholesterol, triglycerides, and BCAAs (P>0.05). In conclusion, The GG genotype of BCAT1 rs9668920 SNP might be a risk factor of T2DM. More studies are required to confirm this finding.