Association of Anthropometric Indices With Midlife Cardiovascular Risk in Young Individuals Without Obesity and Traditional Risk Factors.

BACKGROUND: The aim of this study was to assess how early-adulthood body mass index (BMI) and waist circumference (WC) relate to long-term cardiovascular structure, function, and prognosis in individuals without obesity and with low cardiovascular risk factor (CVRF) burden. METHODS AND RESULTS: A total of 2024 participants aged 18 to 30 from the CARDIA (Coronary Artery Risk Development in Young Adults) study, without obesity and with low CVRFs defined as the absence of cardiovascular disease (CVD), diabetes, hypertension, current smoking, and dyslipidemia were included. A CVRF-optimal subgroup was also defined, with blood pressure<120/80 mm Hg, fasting glucose <100 mg/dL, total cholesterol <200, low-density lipoprotein cholesterol <130, and women with high-density lipoprotein cholesterol ≥50 mg/dL. Coronary artery calcification, carotid intima-media thickness, left ventricular mass, left ventricular ejection fraction, longitudinal peak systolic strain, and diastolic function were assessed in midlife. Cox regression was used to calculate hazard ratios of BMI and WC for all-cause death and CVD events. Logistic regression was used to estimate odds ratios for subclinical CVD. Over 33.9 years (median follow-up), 5.2% (n=105) died, and 2.6% (n=52) had CVD events. Each 1-SD BMI increase was associated with 27% (95% CI, 1.10-1.47), 24% (1.08-1.43), 42% (1.20-1.68), 28% (1.05-1.57), 51% (1.20-1.90), and 49% (1.10-2.02) higher odds of coronary artery calcification presence, increased carotid intima-media thickness, left ventricular hypertrophy, reduced left ventricular ejection fraction, low longitudinal peak systolic strain, and diastolic dysfunction, respectively, in the CVRF-low group. Generally, similar associations were found for WC and in the CVRF-optimal subgroup. No significant associations between BMI and WC with CVD and death were found. CONCLUSIONS: Elevations in BMI and WC among young low-risk individuals, even within the nonobesity range, are associated with midlife cardiovascular health.

Impact of optimal cholesterol levels on subclinical atherosclerosis in the absence of risk factors in young adults.

BACKGROUND AND AIMS: We aimed to assess the association of blood lipids with the prevalence, incidence, and progression of subclinical atherosclerosis among young individuals without dyslipidemia and other traditional cardiovascular risk factors (CVRFs). METHODS: A total of 1270 participants from the Coronary Artery Risk Development in Young Adults (CARDIA) study aged 32-46 years free of cardiovascular disease, diabetes, hypertension, current smoking, and dyslipidemia (total cholesterol [TC] ≥ 240 mg/dL, triglycerides [TG] ≥ 150 mg/dL, low-density lipoprotein cholesterol [LDL-C] ≥ 160 mg/dL, high-density lipoprotein cholesterol [HDL-C] < 40 mg/dL, or taking lipid-lowering medications) were included. A subgroup with optimal lipids within the low-CVRF group was defined with TC < 200 mg/dL, LDL-C < 100 mg/dL, non-HDL-C < 130 mg/dL, and women with HDL-C ≥ 50 mg/dL. RESULTS: 1-SD higher TC (25.9 mg/dL), LDL-C (24.7 mg/dL), and non-HDL-C (26.6 mg/dL) were associated with a greater risk of presence (hazard ratios: 1.30-1.36), incidence (1.30-1.32), and progression (1.31-1.35) of coronary artery calcium (CAC) and a 42-44% greater odds of composite mean carotid intima-media thickness (CIMT) ≥ 75th percentile [780 µm] (p < 0.05). Repeating the analyses in a subset of participants with a CAC score of zero did not alter the association of TC, LDL-C, and non-HDL-C with CIMT. In the subgroup with optimal lipids, these lipid indices remained associated with an increased risk of presence and incidence of CAC and greater CIMT measures. CONCLUSIONS: Among adults aged 32-46 years, in the absence of traditional CVRFs, elevated cholesterol levels, even within what is considered optimal, are associated with atherosclerosis and arteriopathy.

The impact of conventional smoking versus electronic cigarette on the expression of VEGF, PEMPA1, and PTEN in rat prostate.

Background: The use of electronic cigarettes (e-cigarettes), the alternative to conventional smoking, is increasing considerably worldwide; however, their safety is a matter of debate. Several studies have demonstrated their toxic effects, but no study assessed their effects on the prostate. Objective: The current study aimed at evaluating e-cigarettes and conventional smoking prostate toxicity and effects on the expression of vascular endothelial growth factor A (VEGFA), phosphatase and tensin (PTEN), and prostate transmembrane protein androgen induced 1 (PMEPA1). Method: 30 young Wistar rats were categorized into three groups (n = 10) as follows: the control group, the conventional smoking group, and the e-cigarette group. The case groups were exposed to cigarettes or e-cigarettes for 40 minutes, 3 times a day for four months. Serum parameters, prostate pathology, and gene expression were measured at the end of the intervention. Data were analyzed by Graph Pad prism 9. Results: Histopathological findings presented that both types of cigarette-induced hyperemia and induced inflammatory cell infiltration and hypertrophy of smooth muscle of the vascular wall in the e-cigarette group. Expression of PMEPA1, and VEGFA genes significantly increased in conventional (2.67-fold; P = 0.0108, 1.80-fold; P = 0.0461 respectively) and e-cigarettes (1.98-fold; P = 0.0127, 1.34-fold; P = 0.938, respectively) groups compared to the control group. Expression of the PTEN gene non-significantly decreased in the case of groups compared to the control group. Conclusion: We found no significant differences between the two groups in terms of PTEN and PMEPA1 expression, whereas VEGFA was significantly more expressed in a conventional smoking group compared to the e-cigarette group. Therefore, it seems that e-cigarettes could not be taken into account as a better option than conventional smoking, and quitting smoking still is the optimal option.

Role of non-coding RNAs in neuroblastoma.

Neuroblastoma is known as the most prevalent extracranial malignancy in childhood with a neural crest origin. It has been widely accepted that non-coding RNAs (ncRNAs) play important roles in many types of cancer, including glioma and gastrointestinal cancers. They may regulate the cancer gene network. According to recent sequencing and profiling studies, ncRNAs genes are deregulated in human cancers via deletion, amplification, abnormal epigenetic, or transcriptional regulation. Disturbances in the expression of ncRNAs may act either as oncogenes or as anti-tumor suppressor genes, and can lead to the induction of cancer hallmarks. ncRNAs can be secreted from tumor cells inside exosomes, where they can be transferred to other cells to affect their function. However, these topics still need more study to clarify their exact roles, so the present review addresses different roles and functions of ncRNAs in neuroblastoma.

Association between Wrist Circumference and Risk of Any Fracture in Adults: Findings from 15 Years of Follow-Up in the Tehran Lipid and Glucose Study.

We evaluated whether wrist circumference (WrC), as a novel anthropometric measure, is associated with incidences of any fractures. The study population included 8288 adults (45.3% men) aged ≥30 years, who were followed for incidences of any fractures from 31 January 1999 to 16 March 2016. We used Cox proportional hazard models adjusted for well-known risk factors to evaluate the association of WrC, both as continuous and categorical variables (bottom tertile as reference), with incidences of any fractures and major osteoporotic fractures (MOF). Over 15 years of follow-ups, 348 fractures occurred (men = 162). For a 1 cm increase in WrC, hazard ratios (HRs) were 1.18 (95% CI: 1.03-1.35) for incident any fractures and 1.22 (1.01-1.49) for incident MOF. In addition to WrC, age, female sex, lower BMI, higher WC, current smoking, and usage of steroidal medications were significantly associated with the incidences of any fractures. Moreover, participants in the middle and top tertiles of WrC had a higher risk of incidence for any fractures [HR = 1.62 (1.19-2.20) and 1.70 (1.14-2.55), respectively, p-value for trend = 0.012]. We presented WrC as a strong and independent risk factor for incidences of any fractures that might be considered in the risk prediction of bone fracture in Iranian adults.

MicroRNA-383: A tumor suppressor miRNA in human cancer.

Downregulated expression of anti-tumor miR-383 has been found in many kinds of cancer. MiR-383 family members can directly target the 3'-untranslated region (3'-UTR) of the mRNA of some pro-tumor genes to attenuate several cancer-related processes, including cell proliferation, invasion, migration, angiogenesis, immunosuppression, epithelial-mesenchymal transition, glycolysis, chemoresistance, and the development of cancer stem cells, whilst promoting apoptosis. Functionally, miR-383 operates as a tumor inhibitor miRNA in many types of cancer, including breast cancer, hepatocellular carcinoma, gastric cancer, pancreatic cancer, colorectal cancer, esophageal cancer, lung cancer, head and neck cancer, glioma, medulloblastoma, melanoma, prostate cancer, cervical cancer, oral squamous cell carcinoma, thyroid cancer, and B-cell lymphoma. Both pro-tumor and anti-tumor effects have been attributed to miR-383 in ovarian cancer. However, only the pro-tumor effects of miR-383 were reported in cholangiocarcinoma. The restoration of miR-383 expression could be considered a possible treatment for cancer. This review discusses the anti-tumor effects of miR-383 in human cancers, emphasizing their downstream target genes and potential treatment approaches.

Virus, Exosome, and MicroRNA: New Insights into Autophagy.

Autophagy is known as a conserved self-eating mechanism that contributes to cells to degrade different intracellular components (i.e., macromolecular complexes, aggregated proteins, soluble proteins, organelles, and foreign bodies). Autophagy needs formation of a double-membrane structure, which is composed of the sequestered cytoplasmic contents, called autophagosome. There are a variety of internal and external factors involved in initiation and progression of autophagy process. Viruses as external factors are one of the particles that could be associated with different stages of this process. Viruses exert their functions via activation and/or inhibition of a wide range of cellular and molecular targets, which are involved in autophagy process. Besides viruses, a variety of cellular and molecular pathways that are activated and inhibited by several factors (e.g., genetics, epigenetics, and environment factors) are related to beginning and developing of autophagy mechanism. Exosomes and microRNAs have been emerged as novel and effective players anticipated in various stages of autophagy. More knowledge in these pathways and identification of accurate roles of them could help to provide better therapeutic approaches in several diseases such as cancer. We highlighted the roles of viruses, exosomes, and microRNAs in the autophagy processes.

Applications of resveratrol in the treatment of gastrointestinal cancer.

Natural product compounds have lately attracted interest in the scientific community as a possible treatment for gastrointestinal (GI) cancer, due to their anti-inflammatory and anticancer properties. There are many preclinical, clinical, and epidemiological studies, suggesting that the consumption of polyphenol compounds, which are abundant in vegetables, grains, fruits, and pulses, may help to prevent various illnesses and disorders from developing, including several GI cancers. The development of GI malignancies follows a well-known path, in which normal gastrointestinal cells acquire abnormalities in their genetic composition, causing the cells to continuously proliferate, and metastasize to other sites, especially the brain and liver. Natural compounds with the ability to affect oncogenic pathways might be possible treatments for GI malignancies, and could easily be tested in clinical trials. Resveratrol is a non-flavonoid polyphenol and a natural stilbene, acting as a phytoestrogen with anti-cancer, cardioprotective, anti-oxidant, and anti-inflammatory properties. Resveratrol has been shown to overcome resistance mechanisms in cancer cells, and when combined with conventional anticancer drugs, could sensitize cancer cells to chemotherapy. Several new resveratrol analogs and nanostructured delivery vehicles with improved anti-GI cancer efficacy, absorption, and pharmacokinetic profiles have already been developed. This present review focuses on the in vitro and in vivo effects of resveratrol on GI cancers, as well as the underlying molecular mechanisms of action.

Effects of microRNAs and long non-coding RNAs on chemotherapy response in glioma.

Glioma is the most prevalent invasive primary tumor of the central nervous system. Glioma cells can spread and infiltrate into normal surrounding brain tissues. Despite the standard use of chemotherapy and radiotherapy after surgery in glioma patients, treatment resistance is still a problem, as the underlying mechanisms are still not fully understood. Non-coding RNAs are widely involved in tumor progression and treatment resistance mechanisms. In the present review, we discuss the pathways by which microRNAs and long non-coding RNAs can affect resistance to chemotherapy and radiotherapy, as well as offer potential therapeutic options for future glioma treatment.

Long delay in diagnosis of a case with MEN1 due to concomitant presence of AIMAH with insulinoma: a case report and literature review.

BACKGROUND: ACTH-independent macronodular hyperplasia (AIMAH) is an uncommon disorder characterized by massive enlargement of both adrenal glands and hypersecretion of cortisol. Concomitant AIMAH and multiple endocrine neoplasia type1 (MEN1) is rare to our knowledge. CASE PRESENTATION: Herein, we describe a 32 year old woman with long history of prolactinoma and secondary ammonhrea presented with not-severe manifestation of hypoglycemia due to concomitant presence of insulinoma with AIMAH leading to 12 years delay of MEN1 diagnosis. Laboratory tests showed severe hypoglycemia associated with hyper insulinemia (non-fasting blood sugar = 43 mg/dl, insulin = 80.6 µIU /ml, C-peptide = 9.3 ng/ml) hyperparathyroidism (calcium = 10.3 mg/dl, phosphor = 3.1 mg/dl, PTH = 280 pg/ml) and chemical evidence of an ACTH-independent hypercortisolism (serum cortisol value of 3.5, after 1 mg dexamethasone suppression test serum ACTH value of 17 pg/ml, and high urinary cortisol level). Abdominal CT scan demonstrated two enhancing well-defined masses 27*20 mm and 37*30 mm in the tail and body of the pancreas, respectively, and a 36*15 mm mass in left adrenal gland (seven Hounsfield units). Dynamic pituitary MRI revealed a partial empty sella. The physical examination of the patient was unremarkable. Distal pancreatectomy and a left adrenalectomy were performed. After the surgery, we observed clinical and biochemical remission of hyper insulinemia and gradual decrease in urinary cortisol. The histological features of the removed left adrenal gland were consistent with AIMAH. Histological examination of the pancreatic lesions revealed well differentiated neuroendocrine tumors. Genetic abnormalities in the MEN1, heterozygote for pathogenic variant chr11; 645,773,330-64577333AGAC, c.249-252delGTCT, p. (11e85Serfs Ter33) in exon 2 were found. It was recommended the patient undergoes parathyroidectomy as soon as possible. CONCLUSION: Given the history and presentation of our case, we recommend that the clinicians consider the possibility of autonomous cortisol production in MEN1 patients who do not show severe symptoms of hypoglycemia in the presence of insulinoma.

MicroRNA let-7 and viral infections: focus on mechanisms of action.

MicroRNAs (miRNAs) are fundamental post-transcriptional modulators of several critical cellular processes, a number of which are involved in host defense mechanisms. In particular, miRNA let-7 functions as an essential regulator of the function and differentiation of both innate and adaptive immune cells. Let-7 is involved in several human diseases, including cancer and viral infections. Several viral infections have found ways to dysregulate the expression of miRNAs. Extracellular vesicles (EV) are membrane-bound lipid structures released from many types of human cells that can transport proteins, lipids, mRNAs, and miRNAs, including let-7. After their release, EVs are taken up by the recipient cells and their contents released into the cytoplasm. Let-7-loaded EVs have been suggested to affect cellular pathways and biological targets in the recipient cells, and can modulate viral replication, the host antiviral response, and the action of cancer-related viruses. In the present review, we summarize the available knowledge concerning the expression of let-7 family members, functions, target genes, and mechanistic involvement in viral pathogenesis and host defense. This may provide insight into the development of new therapeutic strategies to manage viral infections.

MicroRNAs and exosomes: Cardiac stem cells in heart diseases.

Treating cardiovascular diseases with cardiac stem cells (CSCs) is a valid treatment among various stem cell-based therapies. With supplying the physiological need for cardiovascular cells as their main function, under pathological circumstances, CSCs can also reproduce the myocardial cells. Although studies have identified many of CSCs' functions, our knowledge of molecular pathways that regulate these functions is not complete enough. Either physiological or pathological studies have shown, stem cells proliferation and differentiation could be regulated by microRNAs (miRNAs). How miRNAs regulate CSC behavior is an interesting area of research that can help us study and control the function of these cells in vitro; an achievement that may be beneficial for patients with cardiovascular diseases. The secretome of stem and progenitor cells has been studied and it has been determined that exosomes are the main source of their secretion which are very small vesicles at the nanoscale and originate from endosomes, which are secreted into the extracellular space and act as key signaling organelles in intercellular communication. Mesenchymal stem cells, cardiac-derived progenitor cells, embryonic stem cells, induced pluripotent stem cells (iPSCs), and iPSC-derived cardiomyocytes release exosomes that have been shown to have cardioprotective, immunomodulatory, and reparative effects. Herein, we summarize the regulation roles of miRNAs and exosomes in cardiac stem cells.

Role of non-coding RNAs and exosomal non-coding RNAs in retinoblastoma progression.

Retinoblastoma (RB) is a rare aggressive intraocular malignancy of childhood that has the potential to affect vision, and can even be fatal in some children. While the tumor can be controlled efficiently at early stages, metastatic tumors lead to high mortality. Non-coding RNAs (ncRNAs) are implicated in a number of physiological cellular process, including differentiation, proliferation, migration, and invasion, The deregulation of ncRNAs is correlated with several diseases, particularly cancer. ncRNAs are categorized into two main groups based on their length, i.e. short and long ncRNAs. Moreover, ncRNA deregulation has been demonstrated to play a role in the pathogenesis and development of RB. Several ncRNAs, such as miR-491-3p, miR-613,and SUSD2 have been found to act as tumor suppressor genes in RB, but other ncRNAs, such as circ-E2F3, NEAT1, and TUG1 act as tumor promoter genes. Understanding the regulatory mechanisms of ncRNAs can provide new opportunities for RB therapy. In the present review, we discuss the functional roles of the most important ncRNAs in RB, their interaction with the genes responsible for RB initiation and progression, and possible future clinical applications as diagnostic and prognostic tools or as therapeutic targets.

Novel combination therapy of prostate cancer cells with arsenic trioxide and flutamide: An in-vitro study.

OBJECTIVE: The study objective was to assess the therapeutic potential of Arsenic Trioxide (ATO) and Flutamide combination for metastatic prostate cancer (PCa) treatment. MATERIAL AND METHOD: LNCaP and PC3 cell lines were treated with different concentrations of ATO and PCa conventional drug Flutamide alone and/or in combination to find effective doses and IC50 values. Percentages of apoptotic cells were evaluated by Annexin/PI staining and the proliferative inhibitory effect was assessed by Micro Culture Tetrazolium Test (MTT). Expression of SNAIL, KLK2, E-cadherin, and angiogenesis genes (VEGFA and VEGFC), and apoptosis genes (Bcl2, and P53) were examined by real-time PCR. RESULTS: The combination of Flutamide and ATO significantly increased the percentage of apoptotic cells and inhibited PCa cells proliferation compared with each drug alone in LNCaP and PC3 cell lines. Generally, both cell lines treated with the combination of Flutamide and ATO showed a decrease in expression of KLK2, angiogenesis genes (VEGFA and VEGFC), and apoptosis gene (Bcl2), and an increase in expression of E-cadherin and P53 genes; however, contradictory findings were found regarding SNAIL expression in LNCaP and PC3 cells. CONCLUSION: The combination therapy with ATO and flutamide has augmented the anti-tumor effect on LNCaP and PC3 cells, which probably originates from their potential to induce apoptosis and inhibit the proliferation of PCa cells simultaneously.

Complications of dual growing rod with all-pedicle screw instrumentation in the treatment of early-onset scoliosis.

BACKGROUND: Treatment of early-onset scoliosis (EOS) is still a challenge to patients, families, and surgeons. Previous studies have indicated that EOS patients are at high risk for complications following growth-friendly surgery. This study was performed to evaluate the results and complications of all-pedicle screw dual growing rod instrumentation in the treatment of EOS. METHODS: In an IRB-approved retrospective study, we searched the electronic medical records of our institution for all patients who underwent posterior spinal instrumentation for scoliosis between March 2014 and March 2017. Patients under the age of 10 at the time of surgery who were treated with a growth-friendly technique were then selected. Patients with incomplete records and less than 2 years of follow-up were excluded. Charts, operative notes, clinic visits, and radiographs were extracted. Radiographs were reviewed, and the main curve Cobb angle, thoracic kyphosis, pelvic tilt, pelvic incidence, sacral slope, and proximal junctional angles were measured. We specifically looked for any intra-operative or post-operative complications. Statistical analysis was performed to determine the risk factors of complications. RESULTS: A total of 42 patients with a mean age of 4.8 ± 2.1 years (range, 1.5-8 years) were included in the final analysis. Patients were followed for a median of 34 months (range, 24-55). The major curve was corrected from a mean of 42.9° ± 10.7° to 28.8° ± 9.6° at the latest follow-up. Proximal junctional angles and thoracic kyphosis increased significantly during the follow-up period (both P values < 0.001). A total of 7 complications (17%) were observed. Four patients (10%) developed superficial surgical site infections, all of which resolved with antibiotics and one round of surgical debridement. Three cases (7%) of proximal junctional kyphosis (PJK) were encountered during the study period, none of which required revision surgery. Pre-operative thoracic kyphosis was the only significant risk factor for the development of PJK. CONCLUSIONS: Our findings suggest that in settings without access to magnetically controlled growing rods, dual growing rods with all-pedicle screw instrumentation is still a viable treatment strategy with comparable results and complications. The most common complications are infection and PJK, with the latter being associated with a larger pre-operative thoracic kyphosis.

Postrenal Azotemia in a Gastric Cancer Patient Revealed the Coincidence of Ureteral Metastasis and Contralateral Ureteral Stone: A Case Report.

Metastatic ureteral masses are not rare, but isolated ureteral metastasis from the origin of gastric cancer is rare. Ureteral metastasis is usually unilateral and does not lead to postrenal azotemia unless in single kidney patients. Herein, we describe an 80-year-old man with a history of nonmetastatic gastric cancer who presented with postrenal azotemia due to the coincidence of right distal ureteral metastasis and left distal ureteral stone.

A case of condyloma acuminate after about 30 years of urinary obstructive symptoms.

Condyloma acuminate (CA) is a warty lesion caused by human papilloma virus (HPV) mostly involve the external genitalia. A 65-year-old woman with a compliant of acute urinary retention came to our hospital emergency ward and the retention was resolved by placing a 6 Fr Foley catheter. On physical examination warty lesions on patient's urethral meatus was seen and biopsy was taken. The pathology confirmed the diagnosis of CA. 5-FU was prescribed for a month and the outcome was fully satisfactory. To sum up, CA in female with AUR should be kept in mind.