A case report of prostate cancer with leptomeningeal metastasis and bone marrow involvement.

BACKGROUND: Prostate cancer is the second most common cancer in men. Central nervous system (CNS) involvement in prostate cancer which manifests as cerebral, leptomeningeal, or dural involvement is uncommon and occurs late in the course of disease. CASE: A 60-year-old patient with castration resistant prostate cancer (CRPC) presented with headache and fatigue. Evaluation revealed bone marrow and leptomeningeal involvement. The patient treated by whole brain radiotherapy, leuprolide, weekly docetaxel and daily 1000 mg abiraterone. Complete blood count (CBC) and CNS symptoms improved and the patient is alive after 11 months with excellent performance status. CONCLUSION: Leptomeningeal involvement in prostate cancer is rare and is associated with a poor prognosis but the possibility of such event should be considered in patients with new onset progressive CNS symptoms. New treatment strategies such as combination of docetaxel and abiraterone added to androgen deprivation therapy (triplet therapy) might improve outcome in these patients.

HER2GAN: Overcome the Scarcity of HER2 Breast Cancer Dataset Based on Transfer Learning and GAN Model.

INTRODUCTION: Immunohistochemistry (IHC) is crucial for breast cancer diagnosis, classification, and individualized treatment. IHC is used to measure the levels of expression of hormone receptors (estrogen and progesterone receptors), human epidermal growth factor receptor 2 (HER2), and other biomarkers, which are used to make treatment decisions and predict how well a patient will do. The evaluation of the breast cancer score on IHC slides, taking into account structural and morphological features as well as a scarcity of relevant data, is one of the most important issues in the IHC debate. Several recent studies have utilized machine learning and deep learning techniques to resolve these issues. MATERIALS AND METHODS: This paper introduces a new approach for addressing the issue based on supervised deep learning. A GAN-based model is proposed for generating high-quality HER2 images and identifying and classifying HER2 levels. Using transfer learning methodologies, the original and generated images were evaluated. RESULTS AND CONCLUSION: All of the models have been trained and evaluated using publicly accessible and private data sets, respectively. The InceptionV3 and InceptionResNetV2 models achieved a high accuracy of 93% with the combined generated and original images used for training and testing, demonstrating the exceptional quality of the details in the synthesized images.

The effect of Nigella sativa oil on vascular dysfunction assessed by flow-mediated dilation and vascular-related biomarkers in subject with cardiovascular disease risk factors: A randomized controlled trial.

Cardiovascular diseases (CVD) are the leading causes of mortality worldwide. Flow-mediated dilation (FMD) is a marker of vascular function. Beneficial cardiometabolic effects of Nigella sativa (N. sativa) have been observed. We evaluated the effect of N. sativa oil on FMD, plasma nitrite, and nitrate (NOx) as nitric oxide (NO) metabolites, and inflammatory markers in subjects with CVD risk factors. Fifty participants were randomly assigned to either the N. sativa (two capsules of 500 mg N. sativa oil) or the placebo group (two capsules of 500 mg mineral oil), for 2 months. The brachial FMD, plasma NOx, vascular cellular adhesion molecule-1 (VCAM-1), and intracellular adhesion molecule-1 (ICAM-1) were measured. FMD and plasma NOx levels was significantly increased in the N. sativa group compared to the placebo group (changes: 2.97 ± 2.11% vs. 0.71 ± 3.19%, p < 0.001 for FMD and 4.73 ± 7.25 µmol/L vs. 0.99 ± 5.37 µmol/L, p = 0.036 for plasma NOx). However, there was no significant difference in ICAM-1 and VCAM-1 levels between groups. Therefore, N. sativa oil improves vascular NO and FMD in subjects with cardiovascular risk factors. However, more studies are warranted to confirm the beneficial impacts of the N. sativa oil on vascular inflammation.

ß-D-mannuronic Acid (M2000) and Inflammatory Cytokines in COVID-19; An In vitro Study.

coronavirus disease of 2019 (COVID-19) can be complicated by acute respiratory distress syndrome (ARDS) and may be associated with cytokine storm and multiorgan failure. Anti-inflammatory agents, such as systemic corticosteroids, monoclonal antibodies, and nonsteroidal anti-inflammatory drugs (NSAIDs) can be used for this purpose. In this study, we evaluated the immunomodulatory effect of mannuronic acid (M2000), which is a novel NSAID, on COVID-19-related cytokine storms. This study was conducted in vitro on blood samples of 30 COVID-19 patients who presented with ARDS to a referral center. Peripheral blood mononuclear cells (PBMCs) were isolated from blood samples and incubated with phorbol myristate acetate for 24 hours. M2000 was administered with the dosages of 25 µg/well and 50 µg/well after 4 hours of incubation at 37°C. The quantitative real-time polymerase chain reaction (qRT-PCR) was conducted to assess mRNA gene expression. Enzyme-linked immunosorbent assay (ELISA) was performed to evaluate the supernatant PBMC levels of interleukin (IL)-6, IL-17, tumor necrosis factor (TNF)-α, and interferon (IFN)-γ. Both mRNA expression and the supernatant PBMC levels of IL-17, TNF-α, IL­6, and IFN­Î³ were decreased in PBMCs of COVID-19 patients treated with M2000 compared with the control  group. For the first time, it was observed that M2000 could be effective in alleviating the inflammatory cascade of COVID-19 patients based on an in vitro model. After further studies in vitro and in animal models, M2000 could be considered a novel NSAID drug in COVID-19 patients.

Comparison of ameliorative effects of Taraxacum syriacum and N-acetylcysteine against acetaminophen-induced oxidative stress in rat liver and kidney.

Taraxacum syriacum (TS) with natural antioxidant and pharmacological activities may be considered for treatment of oxidative stress induced by acetaminophen (APAP). The aim of this study was to evaluate the ameliorative effects of the ethanol extract of TS root against hepatorenal toxicity induced by APAP in comparison to N-acetylcysteine (NAC) as a standard drug. Thirty male Wistar rats were randomly divided into five groups. Control group; APAP (1 g/kg) group; APAP-NAC (160 mg/kg) group and APAP-TS100 and APAP-TS200 groups: APAP plus 100 and 200 mg/kg of TS extract, respectively. After 7 days treatment, serum and liver and kidney tissues were prepared and evaluated. TS extract ameliorated the increased lipid peroxidation level and decreased antioxidant enzymes activities and glutathione level in liver and kidney of APAP-treated rats. Moreover, treatment with the TS extract caused significant reduction in the histopathological damages and high levels of serum biochemical markers of hepatic and renal functions after APAP treatment. This study suggests that the extract of TS roots has dose-dependent ameliorative effect against APAP-induced oxidative damage in liver and kidney due to its free radical scavenging and antioxidant properties. The overall efficacy of the extract at 200 mg/kg dose is comparable with NAC.

PIK3CA Mutation Analysis in Iranian Patients with Gastric Cancer

Backgrounda: Aberrant activation of phosphatidylinositol-3 kinases (PI3K)/AKT/mTOR (mammalian target of rapamycin) pathway is a critical event during gastric cancer progression. Selective function of AKT inhibitor AZD5363 in PI3KCA mutant gastric cancer necessitates the assessment of PI3KCA mutations in these patients. Methods: The study included 100 patients with gastric cancer who underwent surgical resection at Imam Reza Hospital, Tehran, Iran, between January 2009 and December 2016. Mutations in codon 1047 of PIK3CA were evaluated by tetra-primer ARMS-PCR and direct sequencing methods. Results: We detected p.H1047R and p.H1047L in eight and three samples, respectively. Also, a significant association was found between PIK3CA mutations and lymphatic invasion. Kaplan-Meier analysis demonstrated no significant differences in overall survival between patients with and without mutations. Conclusion: Our study detected gain-of-function mutations in exon 20 of PI3KCA gene in 11% of gastric cancer patients. Future studies are needed to assess the mutation rate in other regions of this gene to find eligible patients for targeted therapies.

Association of interleukin-1 gene polymorphism with risk of gastric and colorectal cancers in an Iranian population.

BACKGROUND: Chronic inflammation is associated with neoplasms and several types of cancer. Therefore, polymorphisms in the inflammation-related genes could modify the cancer susceptibility. OBJECTIVE: To investigate the associations between IL-1RN VNTR and rs419598 polymorphisms in IL-1 receptor antagonist (IL-1ra) and colorectal cancer (CRC) and gastric cancer (GC) in an Iranian population. METHODS: In this study, 126 cancer cases (91 CRC and 35 GC) and 97 healthy controls were included. Genotyping of IL-1RN VNTR and rs419598 was performed by PCR amplification and PCR-RFLP, respectively. Logistic regression was applied to identify the independent risk factors for colorectal and gastric cancers by computing the odds ratio (OR) and 95% confidence intervals (95% CI). All statistical analyses were performed using the SPSS statistical software. RESULTS: There were significant differences between cancer groups and control group concerning the frequency of A1/A2 genotypes in IL-1RN VNTR polymorphism. The carrier status of IL-1RN* 2 allele was associated with increased risk of CRC (p = 0.0003; OR = 0.02; 95% CI: 0.491-0.85) and GC (p = 0.0006; OR = 0.106; 95% CI: 0.321-0.035). Also, the homozygous ILRN *2/*2 genotype was associated with increased risk of gastric cancer (p = 0.04; OR = 0.133; 95% CI: 0.020-0.908). There was no association between different alleles of rs419598 and CRC and GC. CONCLUSION: This study demonstrates an association between the carrier status of IL-1RN* 2 and CRC and GC in an Iranian population.

Impacts of morphine addiction on spermatogenesis in rats.

BACKGROUND: There are numerous investigations on wide range of issues that disrupt regulatory spermatogenesis, individuals who are exposed to drug abuse faced infertility and immature spermatogenesis. OBJECTIVE: The aim of this study was to evaluate the addiction effects of morphine and its derivatives on rats spermatogenesis. MATERIALS AND METHODS: 40 male Wistar rats were randomly divided into 5 equal groups, which were exposed either with intravenous morphine, naloxone, naloxone and morphine, sham (with normal saline injection) and a control group without infusion. Spermatogenesis was assessed after three months via histological sections with hematoxylin and eosin staining, using a light microscope based on measurement of spermatogonia, spermatocyte, spermatid, and spermatozoa. RESULTS: Those rats that received opioids had changes in spermatogenesis function. The population of spermatogenesis cycle cells at spermatogonia, spermatocyte, spermatid, and spermatozoa stages was significantly decreased in those rats that received opioid in comparison to the control group (p<0.05). Histological studies revealed that changes in different groups of opioid application might affect sperm formation. Sperm count in morphine group was (0±0) and in naloxone group, naloxone+morphine, sham and control were 235±3.77, 220±3.81, 247.12±6.10 and 250±6.54, respectively (p<0.001). CONCLUSION: Morphine could affect all spermatogenesis stages.

Are andropause symptoms related to depression?

BACKGROUND: Andropause is a middle-age condition in which men experience changes in their physical, spiritual and emotional health. The association between andropause and psychological symptoms such as depression are not very clear yet. AIMS: The objective of this study was therefore to determine the association between the 'Aging Males Symptoms Scale' (AMS) and depression. METHODS: A cross sectional study was conducted among 521 old men. To collect data, the AMS and the Patient Health Questionnaires 2 and 9 were used to screen depression, in addition to questions on background and fertility. Multiple linear regression analysis was used to assess the association between andropause symptoms and depression. RESULTS: Based on our results and the AMS score, 51.5% of the study population had clinical symptoms of androgen disorder, 3.7% of which had severe symptoms. There was a strong correlation between the AMS score and depression. Depression, diabetes, cigarette smoking and spousal age retained their significant associations even after entering the relevant demographic, anthropometric, smoking and disease variables in the multivariable model. As a positive predictive factor, depression had the strongest association with AMS. CONCLUSIONS: Based on our results, there is a direct association between andropause symptoms and depression, where the increasing AMS score corresponds with the severity of depression. DISCUSSION: Our results show the need of screening for depression when evaluating andropause symptoms.