The landscape of exosomal non-coding RNAs in breast cancer drug resistance, focusing on underlying molecular mechanisms

Breast cancer (BC) is the most common malignancy among women worldwide. Like many other cancers, BC therapy is challenging and sometimes frustrating. In spite of the various therapeutic modalities applied to treat the cancer, drug resistance, also known as, chemoresistance, is very common in almost all BCs. Undesirably, a breast tumor might be resistant to different curative approaches (e.g., chemo- and immunotherapy) at the same period of time. Exosomes, as double membrane-bound extracellular vesicles 1) secreted from different cell species, can considerably transfer cell products and components through the bloodstream. In this context, non-coding RNAs (ncRNAs), including miRNAs, long ncRNAs (lncRNAs), and circular RNAs (circRNAs), are a chief group of exosomal constituents with amazing abilities to regulate the underlying pathogenic mechanisms of BC, such as cell proliferation, angiogenesis, invasion, metastasis, migration, and particularly drug resistance. Thereby, exosomal ncRNAs can be considered potential mediators of BC progression and drug resistance. Moreover, as the corresponding exosomal ncRNAs circulate in the bloodstream and are found in different body fluids, they can serve as foremost prognostic/diagnostic biomarkers. The current study aims to comprehensively review the most recent findings on BC-related molecular mechanisms and signaling pathways affected by exosomal miRNAs, lncRNAs, and circRNAs, with a focus on drug resistance. Also, the potential of the same exosomal ncRNAs in the diagnosis and prognosis of BC will be discussed in detail

Global burden of peripheral artery disease and its risk factors, 1990–2019 : a systematic analysis for the Global Burden of Disease Study 2019

peripheral artery disease were modelled using the Global Burden of Disease, Injuries, and Risk Factors Study (GBD) 2019 database. Prevalence, disability-adjusted life years (DALYs), and mortality estimates of peripheral artery disease were extracted from GBD 2019. Total DALYs and age-standardised DALY rate of peripheral artery disease attributed to modifiable risk factors were also assessed. Findings In 2019, the number of people aged 40 years and older with peripheral artery disease was 113 million (95% uncertainty interval [UI] 99·2–128·4), with a global prevalence of 1·52% (95% UI 1·33–1·72), of which 42·6% was in countries with low to middle Socio-demographic Index (SDI). The global prevalence of peripheral artery disease was higher in older people, (14·91% [12·41–17·87] in those aged 80–84 years), and was generally higher in females than in males. Globally, the total number of DALYs attributable to modifiable risk factors in 2019 accounted for 69·4% (64·2–74·3) of total peripheral artery disease DALYs. The prevalence of peripheral artery disease was highest in countries with high SDI and lowest in countries with low SDI, whereas DALY and mortality rates showed U-shaped curves, with the highest burden in the high and low SDI quintiles. Interpretation The total number of people with peripheral artery disease has increased globally from 1990 to 2019. Despite the lower prevalence of peripheral artery disease in males and low-income countries, these groups showed similar DALY rates to females and higher-income countries, highlighting disproportionate burden in these groups. Modifiable risk factors were responsible for around 70% of the global peripheral artery disease burden. Public measures could mitigate the burden of peripheral artery disease by modifying risk factors

Mediation effect of social skills between impulsivity with substance abuse in adolescents

The aim of this study is to examine mediation effect of social skills between impulsivity with substance abuse in adolescents. The research sample consists of 616 students of vulnerable high schools in Ardabil City. Together the data of Impulsivity Scale, Matson social skills scale and substance abuse survey were used [Matson, J. L., Rotatori, A. F., & Helsel, W. J. (1983). Development of a rating scale to measure social skills in children: The Matson Evaluation of Social Skills with Youngsters (MESSY). Behaviour Research and therapy, 21(4), 335-340.]. The results show that impulsivity indirectly is associated with substance abuse students (P<0.001) through the effect on social skills. The results indicate that high levels of impulsivity and low-level social skills increase substance abuse in students. These results are consistent with other existing results found in the literature

Therapeutic routine with respiratory exercises improves posture, muscle activity, and respiratory pattern of patients with neck pain : a randomized controlled trial

Neck pain and forward head posture (FHP) are typical in prolonged smartphone users and need to be targeted for treatment. We aimed to compare the effect of a routine therapeutic program with and without respiratory exercises on smartphone users with FHP and non-specific chronic neck pain (NSCNP). Sixty patients (aged 24.7 +/- 2.1 years) with FHP and NSCNP were randomly assigned to the routine therapeutic program (n = 20), combined respiratory exercises with a routine therapeutic program (n = 20), or control (n = 20) groups. At baseline, there was no difference among groups at all variables. Each programme was implemented three times a week for eight weeks. Primary Outcome was pain measured by visual analogue scale (VAS), and secondary ones were forward head angle, the activity of specific muscles, and respiratory patterns, measured by photogrammetry, electromyography and manual, respectively. All outcomes were measured at baseline and eight weeks post-treatment. We used the repeated measures analysis of variance to examine the interaction between time and group, paired t-test for intragroup comparison, one-way analysis of variance for intergroup comparison, and Tukey post hoc test at a significant level 95% was used. There were significant differences in the combined group compared with the routine therapeutic group (P = 0.03) for diaphragm muscle activation, respiratory balance (P = 0.01), and the number of breaths (P = 0.02). There were significant within-group changes from baseline to post-treatment in the combined group for all outcomes above, but no changes in the therapeutic exercise routine group. Despite respiratory pattern, none of the secondary outcomes proved to be superior in the combination group compared to the routine therapeutic program in smartphone users with FHP and NSCNP. Future studies with longer follow-up assessments could strengthen these results.Funding Agencies|Linkoping UniversityTrial registration: Current Controlled Trials using the IRCT website with ID number of, IRCT20200212046469N1 "Prospectively registered" at 04/03/2020.</p

Cervical Ectopic Pregnancy with Placenta Percreta and Gross Hematuria: A Case Report

Background & aim: Cervical ectopic pregnancy is a rare variant of ectopic pregnancy, and placenta percreta is a complex and dangerous condition; patients with these conditions are difficult to manage. In this study, we present a rare case of placenta percreta in cervical pregnancy. Case report: A 32 -year-old woman with 19 weeks of gestation and gross hematuria was admitted to Qaem Hospital in February 2014. Abdominal sonography and magnetic resonance findings indicated percreta. Cystoscopy was performed, which demonstrated invasion of placenta into bladder mucosa. Surgery was planned due to severe hematuria, where cervical ectopic pregnancy with placenta percreta was found. Hysterectomy and partial cystectomy were performed, and to date, the patient is alive and healthy. Conclusion:Placenta percreta with bladder invasion can cause hematuria during pregnancy and early diagnosis can help with successful treatment and management of bleeding

Cervical Ectopic Pregnancy with Placenta Percreta and Gross Hematuria: A Case Report

Background & aim: Cervical ectopic pregnancy is a rare variant of ectopic pregnancy, and placenta percreta is a complex and dangerous condition; patients with these conditions are difficult to manage. In this study, we present a rare case of placenta percreta in cervical pregnancy. Case report: A 32 -year-old woman with 19 weeks of gestation and gross hematuria was admitted to Qaem Hospital in February 2014. Abdominal sonography and magnetic resonance findings indicated percreta. Cystoscopy was performed, which demonstrated invasion of placenta into bladder mucosa. Surgery was planned due to severe hematuria, where cervical ectopic pregnancy with placenta percreta was found. Hysterectomy and partial cystectomy were performed, and to date, the patient is alive and healthy. Conclusion:Placenta percreta with bladder invasion can cause hematuria during pregnancy and early diagnosis can help with successful treatment and management of bleeding

Effect of C/N Ratio and Media Optimization through Response Surface Methodology on Simultaneous Productions of Intra- and Extracellular Inulinase and Invertase from Aspergillus niger ATCC 20611

The study is to identify the extraction of intracellular inulinase (exo- and endoinulinase) and invertase as well as optimization medium composition for maximum productions of intra- and extracellular enzymes from Aspergillus niger ATCC 20611. From two different methods for extraction of intracellular enzymes, ultrasonic method was found more effective. Response surface methodology (RSM) with a five-variable and three-level central composite design (CCD) was employed to optimize the medium composition. The effect of five main reaction parameters including sucrose, yeast extract, NaNO3, Zn+2, and Triton X-100 on the production of enzymes was analyzed. A modified quadratic model was fitted to the data with a coefficient of determination (R2) more than 0.90 for all responses. The intra-extracellular inulinase and invertase productions increased in the range from 16 to 8.4 times in the optimized medium (10% (w/v) sucrose, 2.5% (w/v) yeast extract, 2% (w/v) NaNO3, 1.5 mM (v/v) Zn+2, and 1% (v/v) Triton X-100) by RSM and from around 1.2 to 1.3 times greater than in the medium optimized by one-factor-at-a-time, respectively. The results of bioprocesses optimization can be useful in the scale-up fermentation and food industry

Melatonin and 5-fluorouracil combination chemotherapy : opportunities and efficacy in cancer therapy

Combined chemotherapy is a treatment method based on the simultaneous use of two or more therapeutic agents; it is frequently necessary to produce a more effective treatment for cancer patients. Such combined treatments often improve the outcomes over that of the monotherapy approach, as the drugs synergistically target critical cell signaling pathways or work independently at different oncostatic sites. A better prognosis has been reported in patients treated with combination therapy than in patients treated with single drug chemotherapy. In recent decades, 5-fluorouracil (5-FU) has become one of the most widely used chemotherapy agents in cancer treatment. This medication, which is soluble in water, is used as the first line of anti-neoplastic agent in the treatment of several cancer types including breast, head and neck, stomach and colon cancer. Within the last three decades, many studies have investigated melatonin as an anti-cancer agent; this molecule exhibits various functions in controlling the behavior of cancer cells, such as inhibiting cell growth, inducing apoptosis, and inhibiting invasion. The aim of this review is to comprehensively evaluate the role of melatonin as a complementary agent with 5-FU-based chemotherapy for cancers. Additionally, we identify the potential common signaling pathways by which melatonin and 5-FU interact to enhance the efficacy of the combined therapy

Role of long noncoding RNAs in pathological cardiac remodeling after myocardial infarction: An emerging insight into molecular mechanisms and therapeutic potential

Myocardial infarction (MI) is the leading cause of heart failure (HF), accounting for high mortality and morbidity worldwide. As a consequence of ischemia/reperfusion injury during MI, multiple cellular processes such as oxidative stress-induced damage, cardiomyocyte death, and inflammatory responses occur. In the next stage, the proliferation and activation of cardiac fibroblasts results in myocardial fibrosis and HF progression. Therefore, developing a novel therapeutic strategy is urgently warranted to restrict the progression of pathological cardiac remodeling. Recently, targeting long non-coding RNAs (lncRNAs) provided a novel insight into treating several disorders. In this regard, numerous investigations have indicated that several lncRNAs could participate in the pathogenesis of MI-induced cardiac remodeling, suggesting their potential therapeutic applications. In this review, we summarized lncRNAs displayed in the pathophysiology of cardiac remodeling after MI, emphasizing molecular mechanisms. Also, we highlighted the possible translational role of lncRNAs as therapeutic targets for this condition and discussed the potential role of exosomes in delivering the lncRNAs involved in post-MI cardiac remodeling