Impact of Sustained Exogenous Irisin Myokine Administration on Muscle and Myocyte Integrity in Sprague Dawley Rats.

Irisin is an exercise-induced myokine implicated as a fundamental mediator of physical activity benefits. The aim of the present study was to investigate the role of the chronic administration model of irisin on the physiological and molecular status of skeletal muscle. A total of 20 female Sprague Dawley rats (250 ± 40 g) were implanted with an irisin-loaded osmotic pump (5 µg/kg/day) for 42 days; in addition, 3 females received a single subcutaneous injection of irisin (5 µg/kg). On a weekly basis for six weeks, animals were weighed and blood samples were collected. After 42 days, hind muscle biopsies were collected for histology and gene analysis. Serum irisin, clinical biochemistry, and histopathology were quantified and evaluated. Genes encoding for different physiological muscle activities, such as oxidative stress, fatty acid metabolism, muscle hypertrophy, mitochondrial fusion, and aging were assayed. The results showed a significant reduction in body weight percentage and creatine kinase level without affecting the morphological characteristics of skeletal muscle. Significant changes were noted in genes involved in muscle physiological activity, growth, and aging, as well as genes encoding for the antioxidant system, fatty acid oxidation processes, and mitochondrial fusion. In conclusion, exogenous irisin can induce the same physiological and molecular mechanisms that might be induced by exercise.

The Role of Interventional Irisin on Heart Molecular Physiology.

Irisin, encoded by the FNDC5 (fibronectin type III domain containing 5) gene, is a novel myokine that has been implicated as an essential mediator of exercise benefits. Effects of irisin on heart physiology is still ambiguous. This study aimed to evaluate the impact of exogenous administration of irisin on heart physiology and the pharmacokinetic profile of pump-administered irisin. To do so, Sprague Dawley rats were implanted with an irisin-loaded osmotic pump (5 µg/kg/day) for 42 days, and other animals were administered with single bolus subcutaneous injections of irisin (5 µg/kg). Body weights and blood samples were collected weekly for 42 days for serum irisin quantification and histopathology. Clinical biochemistry analyses were performed. Heart mRNA expression was assessed in 26 selected genes. Chronic interventional exogenous irisin significantly reduced body weight without affecting the heart myocyte size and significantly reduced creatine kinase enzyme level. Blood CBC, serum biochemistry, and heart morphology were normal. Gene expression of FNCD5, Raf1, CPT1, IGF-1, and CALCIN, encoding for heart physiology, increased while PGC1, Nox4, and Mfn1 significantly decreased. Nevertheless, irisin increased the expression of cardioprotective genes and inhibited some genes that harm heart physiology. Administration of irisin promotes myocardial functions and could be translated into clinical settings after preclinical profiling.

Association of obesity with COVID-19 diseases severity and mortality: A meta-analysis of studies.

Background: The literature on COVID-19 infection is growing every single day, and evidence of presence or absence of association between obesity and COVID-19 adverse outcomes should be revisited. Therefore, this study summarizes the pooled association of obesity with COVID-19 adverse outcomes and mortality. Methods: We searched PubMed and Science direct databases using specific terms and defined criteria. Data were analyzed using Comprehensive Meta-Analysis V2 (Biostat, Englewood, NJ, USA)) random-effect models were used to calculate the odds ratio (OR) with 95% confidence intervals (95% CIs) of infection severity and mortality associated with obesity. Results: Results revealed that obesity is not associated with COVID-19 mortality (OR = 1.1; 95%CI: 0.8 to 1.3) but with other adverse outcomes (OR = 2.4; 95%CI: 1.7 to 3.3). Conclusion: Our findings support previous findings that obesity is associated with COVID-19 severity.

Associations of pre-existing cardiovascular morbidity with severity and the fatality rate in COVID-19 patients: a systematic review and meta-analysis.

Objectives: The aim of this study was to evaluate the association of pre-existing cardiovascular comorbidities, including hypertension and coronary heart disease, with coronavirus disease 2019 (COVID-19) severity and mortality. METHODS: PubMed, ScienceDirect, and Scopus were searched between January 1, 2020, and July 18, 2020, to identify eligible studies. Random-effect models were used to estimate the pooled event rates of pre-existing cardiovascular disease comorbidities and odds ratio (OR) with 95% confidence intervals (95% CIs) of disease severity and mortality associated with the exposures of interest. RESULTS: A total of 34 studies involving 19,156 patients with COVID-19 infection met the inclusion criteria. The prevalence of pre-existing cardiovascular disease in the included studies was 14.0%. Pre-existing cardiovascular disease in COVID-19 patients was associated with severe outcomes (OR, 4.1; 95% CI, 2.9 to 5.7) and mortality (OR, 6.1; 95% CI, 2.9 to 12.7). Hypertension and coronary heart disease increased the risk of severe outcomes by 2.6 times (OR, 2.6; 95% CI, 1.9 to 3.6) and 2.5 times (OR, 2.5; 95% CI, 1.7 to 3.8), respectively. No significant publication bias was indicated. Conclusion: COVID-19 patients with pre-existing cardiovascular comorbidities have a higher risk of severe outcomes and mortality. Awareness of pre-existing cardiovascular comorbidity is important for the early management of COVID-19.

A Case-Control Study of the Luteinizing Hormone Level in Luteinizing Hormone Receptor Gene (rs2293275) Polymorphism in Polycystic Ovarian Syndrome Females.

BACKGROUND: Polycystic ovary syndrome (PCOS) is a common heterogeneous disorder characterized by chronic anovulation, infertility, polycystic ovaries, and hyperandrogenic signs. OBJECTIVE: The aim of this study was to determine the association of luteinizing hormone/chorionic gonadotropin hormone receptor LHCGR polymorphism (rs2293275) with oligomenorrhea, amenorrhea, hirsutism, acne, infertility, LH, LH/FSH ratio, and body mass index (BMI) among PCOS females. METHODS: This genetic case-control study recruited 55 PCOS and 55 control females, diagnosed based on the Rotterdam criteria. LH and FSH were measured by the Roche cobas c 502 automated analyzer. Genotypic analysis was carried out using the polymerase chain reaction-restriction fragment length polymorphism and restriction endonuclease digestion. RESULTS: BMI was higher for PCOS patients (28.5 ± 6.59) compared to controls (25.1 ± 5.77), and ovulatory dysfunction was seen among 90% of PCOS females. Oligomenorrhea was common in PCOS (73%), and hirsutism and acne were detected in PCOS (80% and 40%; respectively). LH ≥10 were recoded among 51%, while LH/FSH ≥1.5 was recorded among 33% PCOS females. There is a statistical difference between rs2293275 polymorphism in the AG genotype between PCOS patients and controls. PCOS patients have a significantly higher mean LH level compared to controls (8.36 ± 4.86 and 5.67 ± 2.51, respectively) and showed higher LH/FSH value (1.46 ± 0.81) compared to (0.87 ± 0.30) controls. GG and AG genotypes of LHCGR showed statistically significant higher LH (8.22 ± 4.11; 9.02 ± 3.87) and LH/FSH values (1.57 ± 0.56; 1.64 ± 0.89) compared to controls. CONCLUSION: LHCGR (rs2293275) GA and GG genetic variants could modulate the hormonal levels of PCOS LH levels and the LH/FSH ratio and associated with hirsutism, oligomenorrhea, BMI, and LH/FSH ratio as risk factors.

Vitamin B12 enhances the antitumor activity of 1,25-dihydroxyvitamin D3 via activation of caspases and targeting actin cytoskeleton.

BACKGROUND: 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) is an effective anticancer agent, and when combined with other agents it shows superior activities. Vitamin B12 has been shown to contribute to increasing the effectiveness of anticancer drugs when used in combination. Thus, the current study aimed at investigating the anticancer potential of the combination of 1,25(OH)2D3 and vitamin B12. METHODS: MTT assay was used to determine the cytotoxic activity of combining 1,25(OH)2D3 and vitamin B12 against six different cancer cell lines and one normal cell line. The surviving fraction after clonogenic assay was measured, and the effects of 1,25(OH)2D3/B12 combination on the activity of different caspases, cell adhesion, actin cytoskeleton, cell morphology, and percentage of polarized cells were evaluated. RESULTS: Vitamin B12 did not cause cytotoxicity, however, it enhanced the cytotoxicity of 1,25(OH)2D3 against cancer cells. The cytotoxic effects of 1,25(OH)2D3 and its combination with vitamin B12 was not evident in the normal mammary MCF10A cell line indicating cancer cell-specificity. The cytotoxic effects of 1,25(OH)2D3/B12 combination occurred in a dose-dependent manner and was attributed to apoptosis induction which was mediated by caspase 4 and 8. Moreover, 1,25(OH)2D3/B12-treated cells showed enhanced inhibition of clonogenic tumor growth, reduced cell adhesion, reduced cell area, reduced percentage of cell polarization, and disorganized actin cytoskeleton resulting in reduced migratory phenotype when compared to cells treated with 1,25(OH)2D3 alone. CONCLUSION: 1,25(OH)2D3 and vitamin B12 exhibited synergistic anticancer effects against different cancer cell lines. The combination therapy of 1,25(OH)2D3 and vitamin B12 may provide a potential adjunctive treatment option for some cancer types.

Screening for non-invasive risk factors of type 2 diabetes in overweight and obese schoolchildren.

INTRODUCTION: The prevalence of type 2 diabetes mellitus (T2DM) is increasing among young people worldwide. The American Diabetes Association has defined the risk factors that are associated with this increased risk for developing T2DM in youths. OBJECTIVE: To explore school children at high-risk for T2DM in Jordan. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted. The children were 10-14.9 years old. Weight, height, and waist circumference were measured, and the body mass index Z score (BMI) was determined. The waist to height ratio (WHtR) was calculated. Blood pressure was measured and three child́s risk factors were identified. RESULTS: Eight hundred and seventy-one schoolchildren were screened; 26.0% were overweight and 19.3% were obese. The most common risk factor among overweight and obese children, accounting for 80.4%, was a positive family history of type 2 diabetes mellitus in first- or second-degree relatives. Children born to mothers with diabetes or gestational diabetes mellitus during the child's gestation represented 17.3%, and around 26.8% were found to have hypertension (stage 1 or 2). In relation to the risk factors, 12.6% presented no risk factors; 54.0% had at least one factor; 29.1% two risk factors and 4.3% had three risk factors. CONCLUSION: Risk factors for T2DM are very common. Around 54% had one risk factor. Strategies aimed at reducing risk factors for T2DM, especially obesity, among Jordanian school children are urgently needed.

Correlates of SARS-CoV-2 Variants on Deaths, Case Incidence and Case Fatality Ratio among the Continents for the Period of 1 December 2020 to 15 March 2021.

The outbreak of coronavirus disease 2019 (COVID-19), by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), has quickly developed into a worldwide pandemic. Mutations in the SARS-CoV-2 genome may affect various aspects of the disease including fatality ratio. In this study, 553,518 SARS-CoV-2 genome sequences isolated from patients from continents for the period 1 December 2020 to 15 March 2021 were comprehensively analyzed and a total of 82 mutations were identified concerning the reference sequence. In addition, associations between the mutations and the case fatality ratio (CFR), cases per million and deaths per million, were examined. The mutations having the highest frequencies among different continents were Spike_D614G and NSP12_P323L. Among the identified mutations, NSP2_T153M, NSP14_I42V and Spike_L18F mutations showed a positive correlation to CFR. While the NSP13_Y541C, NSP3_T73I and NSP3_Q180H mutations demonstrated a negative correlation to CFR. The Spike_D614G and NSP12_P323L mutations showed a positive correlation to deaths per million. The NSP3_T1198K, NS8_L84S and NSP12_A97V mutations showed a significant negative correlation to deaths per million. The NSP12_P323L and Spike_D614G mutations showed a positive correlation to the number of cases per million. In contrast, NS8_L84S and NSP12_A97V mutations showed a negative correlation to the number of cases per million. In addition, among the identified clades, none showed a significant correlation to CFR. The G, GR, GV, S clades showed a significant positive correlation to deaths per million. The GR and S clades showed a positive correlation to number of cases per million. The clades having the highest frequencies among continents were G, followed by GH and GR. These findings should be taken into consideration during epidemiological surveys of the virus and vaccine development.

Optimal therapeutic adropin dose intervention in mice and rat animal models: A systematic review.

BACKGROUND AND AIM: Adropin is a hormone encoded by the Enho gene, which is associated with energy homeostasis. Preclinical studies using animal models have shown that adropin plays a role in enhancing glucose homeostasis and dyslipidemia. Lately, several studies on animal models have been performed to examine the therapeutic and pathophysiological effects of adropin in many disorders. The aim of this systematic review was to identify the ideal adropin dose in mice and rat animal models. MATERIALS AND METHODS: We systematically searched PubMed, Science Direct, and Scopus databases from 2008 to 2020. The terms used in the search were "adropin," "adropin doses in animal models," "glucose homeostasis related to adropin," and "adropin therapeutic effects on rats and mice." Articles that included non-adropin doses, in vitro studies, and factors affecting adropin levels were excluded from the study. RESULTS: Of the total 179 qualified studies, six studies were included. We found that a daily injection of 450 nmol/kg of adropin for 3 days might be considered the optimum dose of effect in mice, whereas injection of 2.1 mg/kg once a day for 10 successive days might be the optimal effective dose in rats. CONCLUSION: Additional investigations are needed to determine the optimum dose of adropin to be used as a therapeutic intervention depending on the animal model.

New SARS-CoV-2 Variant from Jordan.

A variant of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) from Jordan was identified during the second wave of infection. The genome of this variant has a unique set of mutations that suggest local evolution. Due to the continuous emergence of new variants worldwide, molecular surveillance is crucial for fighting the pandemic.

Screening for non-invasive risk factors of type 2 diabetes in overweight and obese schoolchildren.

INTRODUCTION: The prevalence of type 2 diabetes mellitus (T2DM) is increasing among young people worldwide. The American Diabetes Association has defined the risk factors that are associated with this increased risk for developing T2DM in youths. OBJECTIVE: To explore school children at high-risk for T2DM in Jordan. MATERIALS AND METHODS: A descriptive cross-sectional study was conducted. The children were 10-14.9 years old. Weight, height, and waist circumference were measured, and the body mass index Z score (BMI) was determined. The waist to height ratio (WHtR) was calculated. Blood pressure was measured and three child́s risk factors were identified. RESULTS: Eight hundred and seventy-one schoolchildren were screened; 26.0% were overweight and 19.3% were obese. The most common risk factor among overweight and obese children, accounting for 80.4%, was a positive family history of type 2 diabetes mellitus in first- or second-degree relatives. Children born to mothers with diabetes or gestational diabetes mellitus during the child's gestation represented 17.3%, and around 26.8% were found to have hypertension (stage 1 or 2). In relation to the risk factors, 12.6% presented no risk factors; 54.0% had at least one factor; 29.1% two risk factors and 4.3% had three risk factors. CONCLUSION: Risk factors for T2DM are very common. Around 54% had one risk factor. Strategies aimed at reducing risk factors for T2DM, especially obesity, among Jordanian school children are urgently needed.

Cerebrovascular comorbidity, high blood levels of C-reactive protein and D-dimer are associated with disease outcomes in COVID-19 patients.

The emerging coronavirus disease (COVID-19) swept the world, affecting more than 200 countries and territories. As of August 22, 2020, the pandemic infected more than 23,329,752 including 807,054 patients who have died. Although the main clinical features of the pandemic disease are respiratory, cerebrovascular comorbidities emerged as one of the leading causes of death associated with COVID-19. Different case reports have indicated that C-reactive protein (CRP) and D-dimer (pro-inflammatory biomarkers) were elevated in COVID-19 patients, which can significantly increase the risk of ischemic stroke. Available data on cerebrovascular complications in COVID-19 patients were collected and a meta-analysis was designed and carried out to evaluate the risk of severity and mortality associated with high levels of CRP and D-dimer levels in COVID-19 patients. In addition, we aimed to describe the overall event rate of pre-existing cerebrovascular disease in COVID-19 patients. In our analysis, 5,614 cases have been studied, out of these patients 164 cases have developed cerebrovascular comorbities. Cerebrovascular comorbidity increased the risk of disease severity (odd ratio = 4.4; 95% CI: 1.48 to 12.84) and mortality (odd ratio = 7.0; 95% CI: 2.56 to 18.99). Statistical analyses showed that CRP and D-dimer serum levels were elevated by six-folds in the severe cases of COVID-19 patients. This significant increase in these two proteins levels can serve as a vital indicator for COVID-19 patients who are at increased risk of severe COVID-19 cerebrovascular complications, such as stroke.

The optimal therapeutic irisin dose intervention in animal model: A systematic review.

BACKGROUND AND AIM: Irisin, a novel myocyte-secreted hormone, was proposed to mediate some of the beneficial effects of exercise such as browning of adipocytes, thermogenesis, and metabolic homeostasis. Recently, several animals' models' studies have been performed to investigate the therapeutic impact of irisin in several disorders. Several interventional trials used different doses. However, optimum dose was not determined. This systematic review aims to identify the optimal dose of interventional irisin in mice and rat animal models. MATERIALS AND METHODS: Online databases PubMed, Google Scholar, and Springer were systematically searched from 2012 to 2019. The words searched were irisin, irisin and animal model, physical activity, and irisin and irisin dosage. Non-irisin doses, in vitro studies, and factors influencing irisin levels were excluded. RESULTS: Eleven of the total 391 qualifying studies were included. A daily injection of 500 µg/kg irisin may be the optimum dose of effect in mice and rats. CONCLUSION: More studies are required to determine the optimum dose of irisin to be used as a therapeutic intervention based on animal model.

Risk of using hydroxychloroquine as a treatment of COVID-19.

The emerging COVID-19 pandemic poses a threat to the global health care system. Given the lack of antiviral therapies or vaccines for the disease, the antimalarial drug hydroxychloroquine (HCQ) obtained much attention as a treatment for COVID-19. However, there are limited and uncertain clinical data to support the beneficial effect of this drug in COVID-19 treatment. HCQ has several side effects and warnings, including blindness, heart failure, and renal toxicity, even with recommended doses. For severe cases of COVID-19 or in patients with preexisting conditions, administering such a drug could be fatal, particularly when taken at high doses or in combination with other antibiotics. However, further well-designed studies that would address the optimal dose, duration of treatment, possible side effects, and long-term usage outcomes are needed to make the final decision. In this paper, we aim to discuss the risk of using HCQ in treating COVID-19 patients, including its possible side effects.

The Human Coronavirus Disease COVID-19: Its Origin, Characteristics, and Insights into Potential Drugs and Its Mechanisms.

The emerging coronavirus disease (COVID-19) swept across the world, affecting more than 200 countries and territories. Genomic analysis suggests that the COVID-19 virus originated in bats and transmitted to humans through unknown intermediate hosts in the Wuhan seafood market, China, in December of 2019. This virus belongs to the Betacoronavirus group, the same group of the 2003 severe acute respiratory syndrome coronavirus (SARS-CoV), and for the similarity, it was named SARS-CoV-2. Given the lack of registered clinical therapies or vaccines, many physicians and scientists are investigating previously used clinical drugs for COVID-19 treatment. In this review, we aim to provide an overview of the CoVs origin, pathogenicity, and genomic structure, with a focus on SARS-CoV-2. Besides, we summarize the recently investigated drugs that constitute an option for COVID-19 treatment.

The rs2236609 Polymorphism Is Related to Increased Risk Susceptibility of Atrial Fibrillation.

INTRODUCTION: Genetic variations in the slow component of the delayed rectifier potassium channels (IKs) are reported to contribute to an increased susceptibility to arrhythmias. This study aims to investigate the frequency and the possible association of the rs2236609 polymorphism in the KCNE1 gene and the risk of atrial fibrillation (AF). METHODS: This was a case-control study that recruited 100 patients suffering from AF (mean age 49.4 ± 15.1 years), and a control group of 95 healthy participants older than 55 years (mean age 59.8 ± 4.1 years) with no history of cardiovascular disease, hypertension, or diabetes. Genomic DNA was extracted from whole peripheral blood, and the desired fragment was amplified using polymerase chain reaction followed by restriction digestion with the NspI restriction enzyme. RESULTS: The results showed a significant difference between the single-nucle-otide polymorphism variations in AF patients and controls (p < 0.022). The risk of AF in the GG genotype was significantly decreased (odds ratio [OR] 0.42; 95% confidence interval [Cl] 0.23-0.79). The risk of AF in the GA (OR 2.12; 95% Cl 1.11-4.06) and AA (OR 2.28, 95% Cl 0.57-9.1) genotypes was significantly increased. The odds of developing AF according to A allele counting was significantly increased (OR 2.1; 95% Cl 1.2608-3.638; p = 0.0048). CONCLUSION: Our results showed a significant increase in AF risk in people carrying the A allele, while the G allele might be considered as a protective allele.

Coronavirus drugs: Using plasma from recovered patients as a treatment for COVID-19.

The ongoing COVID-19 pandemic has infected nearly 3,582,233 individuals with 248,558 deaths since it was first identified in human populations in December 2019 in Wuhan, China. No antiviral therapies or vaccines are available for their treatment or prevention. Passive immunization PI through broadly neutralizing antibodies that bind to the specific antigens of SARS-CoV 2 might be a potential solution to address the immediate health threat of COVID-19 pandemic while vaccines are being developed. The PI approach in treating COVID-19 is discussed herein, including a summary of its historical applications to confront epidemics.

Linkage Between Obesity Leptin and Breast Cancer.

Many cancers might be influenced by obesity, including breast cancer, the leading cause of cancer death among women. Obesity is a complex state associated with multiple physiological and molecular changes capable of modulating the behavior of breast tumor cells and the surrounding microenvironment. This review discussed the inverse association between obesity and breast cancer among premenopausal breast cancer females and the positive association among postmenopausal. Four mechanisms may link obesity and breast cancer including leptin and leptin receptor expression, adipose chronic inflammation, sex hormone alternation, and insulin and insulinlike growth factor 1 (IGF-1) signaling. Leptin has been involved in breast cancer initiation, development, and progression through signaling transduction network. Leptin functions are strengthened through cross talk with multiple oncogenes, cytokines, and growth factors. Adipose chronic inflammation promotes cancer growth and angiogenesis and modifies the immune responses. A pro-inflammatory microenvironment at tumor site promotes cytokines and pro-inflammatory mediators adjacent to the tumor. Leptin stimulates pro-inflammatory cytokines and promotes T-helper 1 responses. Obesity is common of chronic inflammation. In obese patients, white adipose tissue (WAT) will promote pro-inflammatory mediators that will encourage tumor growth and WAT inflammation. Sex hormone alternation of estrogens is associated with increased risk for hormone-sensitive breast cancers. Estrogens cause tumorigenesis by its effect on signaling pathways that lead to DNA damage, stimulation angiogenesis, mutagenesis, and cell proliferation. In postmenopausal females, and due to termination of ovarian function, estrogens were produced extra gonadally, mainly in peripheral adipose tissues where adrenal-produced androgen precursors are converted to estrogens. Active estradiol leads to breast cancer development by binding to ERα, which is modified by receptor's interaction of various signal transduction pathways. Hyperinsulinemia and IGF-1 activate the MAPK and PI3K pathways, leading to cancer-promoting effects. Cross talk between insulin/IGF and estrogen signaling pathways promotes hormone-sensitive breast cancer development. Hyperinsulinemia is a risk factor for breast cancer that explains the obesity-breast cancer association. Controlling IGF-1 level and targeting IGF-1 receptors among different breast cancer subtypes may be useful for breast cancer treatment. This review discussed several leptin signaling pathways, highlighting the potential advantage of targeting leptin as a potential target of the novel therapeutic strategies for breast cancer treatment.

Reduction in breast cancer susceptibility due to XbaI gene polymorphism of alpha estrogen receptor gene in Jordanians.

Breast cancer is a global health concern among women worldwide. Estrogen receptor alpha (ERα) mediates diverse polymorphic effects in breast tissues that may relate to breast cancer susceptibility. The aim of this study was to evaluate the effect of -397 PvuII (T/C) and -351 XbaI (A/G) restriction fragment length polymorphism within intron 1 of ERα, and its effect on breast cancer susceptibility. A total of 156 women who were histopathologically diagnosed with breast cancer and 142 healthy Jordanian women were enrolled in this case-control study. Genomic DNA was extracted from whole peripheral blood, and the desired fragment was amplified using polymerase chain reaction followed by restriction digestion with PvuII and XbaI restriction enzymes. The results showed no significant association between PvuII polymorphism and breast cancer risk. However, a significant association was found between XbaI polymorphism and reduction in breast cancer risk within the "x" allele of heterozygotes (odds ratio [OR] 0.199, 95% confidence interval [CI] 0.09-0.044) and heterozygotes (OR 0.208, 95% CI 0.09-0.047). The combined analysis of PvuII and XbaI polymorphisms revealed a synergistic effect of Pp/Xx and pp/xx genotypes and a significant reduction in breast cancer risk with these genotypes. The results also showed no statistical differences among PvuII or XbaI polymorphisms based on stage, ER, progesterone receptor and expression of hormone receptor such as human epidermal growth factor receptor 2. This case-control study showed that XbaI polymorphism of alpha estrogen gene modified and reduced breast cancer susceptibility among Jordanians.

Vitamin D and Breast Cancer: Latest Evidence and Future Steps.

Vitamin D (the sunshine vitamin) plays a vital role in calcium homeostasis, skeletal metabolism, and immune, cardiovascular, and reproductive systems' functions. The worldwide prevalence of vitamin D deficiency is approximately 1 billion. Vitamin D deficiency is a serious health problem with numerous health consequences; it is associated with diabetes, rheumatic arthritis, Parkinson, Alzheimer diseases, osteomalacia, osteoporosis, and fractures in adults and cancers. Many reports showed an inverse association between serum vitamin D concentration and incidence of several cancers, including breast, colorectal, kidney, lung, and pancreatic. About 20 different cancers have incidence rates inversely related to solar UV-B doses and serum vitamin D concentration. Considering the rising incidence of breast cancer and high prevalence of vitamin D deficiency, this review aimed to reflect an association between serum vitamin D concentration and breast cancer risk, reveal the link between vitamin D receptor genetic polymorphisms and breast cancer risk, and review the relationship between vitamin D level, breast cancer risk, and prognostic factors such as tumor stage, grade, size, lymph node involvement, and hormone receptor status.