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Abstract Background: Although not fully understood, oxidative stress has been implicated in the pathogenesis of different autoimmune diseases such as systemic sclerosis. Accumulating evidence indicates that oxidative stress can induce mitochondrial DNA (mtDNA) damage and variations in mtDNA copy number (mtDNAcn). Objective: The aim of this study was to explore mtDNAcn and oxidative DNA damage byproducts in peripheral blood of patients with systemic sclerosis and healthy controls. Methods: Forty six patients with systemic sclerosis and forty nine healthy subjects were studied. Quantitative real-time PCR used to measure the relative mtDNAcn and the oxidative damage (oxidized purines) of each sample. Results: The mean mtDNAcn was lower in patients with systemic sclerosis than in healthy controls whereas the degree of mtDNA damage was significantly higher in cases as compared to controls. Moreover, there was a negative correlation between mtDNAcn and oxidative DNA damage. Study limitations: The lack of simultaneous analysis and quantification of DNA oxidative damage markers in serum or urine of patients with systemic sclerosis and healthy controls. Conclusion: These data suggest that alteration in mtDNAcn and increased oxidative DNA damage may be involved in the pathogenesis of systemic sclerosis.

Niloofar Arsalan, 1,* Elahe Hassan Kashi, 2,* Anwarul Hasan, 3, 4 Mona Edalat Doost, 5 Behnam Rasti, 6 Bilal Ahamad Paray, 7 Mona Zahed Nakhjiri, 1 Soyar Sari, 2 Majid Sharifi, 8 Koorosh Shahpasand, 9 Keivan Akhtari, 10 Setareh Haghighat, 5 Mojtaba Falahati 8 1Department of Biology, Faculty of Basic Sciences, Lahijan Branch, Islamic Azad University (IAU), Lahijan, Guilan, Iran; 2Department of Cellular and Molecular Biology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 3Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar; 4Biomedical Research Centre, Qatar University, Doha 2713, Qatar; 5Department of Microbiology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 6Department of Microbiology, Faculty of Basic Sciences, Islamic Azad University (IAU), Lahijan, Guilan, Iran; 7Department of Zoology, College of Science, King Saud University, Riyadh 11451, Saudi Arabia; 8Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Tehran Medical Sciences, Islamic Azad University, Tehran, Iran; 9Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology (RI-SCBT), Tehran, Iran; 10Department of Physics, University of Kurdistan, Sanandaj, Iran*These authors contributed equally to this workCorrespondence: Mojtaba Falahati; Anwarul Hasan Email mojtaba.falahati@alumni.ut.ac.ir; ahasan@qu.edu.qaAim: The interaction of NPs with biological systems may reveal useful details about their pharmacodynamic, anticancer and antibacterial effects.Methods: Herein, the interaction of as-synthesized Co 3O 4 NPs with HSA was explored by different kinds of fluorescence and CD spectroscopic methods, as well as molecular docking studies. Also, the anticancer effect of Co 3O 4 NPs against leukemia K562 cells was investigated by MTT, LDH, caspase, real-time PCR, ROS, cell cycle, and apoptosis assays. Afterwards, the antibacterial effects of Co 3O 4 NPs against three pathogenic bacteria were disclosed by antibacterial assays.Results: Different characterization methods such as TEM, DLS, zeta potential and XRD studies proved that fabricated Co 3O 4 NPs by sol-gel method have a diameter of around 50 nm, hydrodynamic radius of 177 nm with a charge distribution of − 33.04 mV and a well-defined crystalline phase. Intrinsic, extrinsic, and synchronous fluorescence as well as CD studies, respectively, showed that the HSA undergoes some fluorescence quenching, minor conformational changes, microenvironmental changes as well as no structural changes in the secondary structure, after interaction with Co 3O 4 NPs. Molecular docking results also verified that the spherical clusters with a dimension of 1.5 nm exhibit the most binding energy with HSA molecules. Anticancer assays demonstrated that Co 3O 4 NPs can selectively lead to the reduction of K562 cell viability through the cell membrane damage, activation of caspase-9, -8 and -3, elevation of Bax/Bcl-2 mRNA ratio, ROS production, cell cycle arrest, and apoptosis. Finally, antibacterial assays disclosed that Co 3O 4 NPs can stimulate a promising antibacterial effect against pathogenic bacteria.Conclusion: In general, these observations can provide useful information for the early stages of nanomaterial applications in therapeutic platforms.Keywords: cobalt oxide, nanoparticle, synthesis, spectroscopy, docking, anticancer, antibacterial

Background and Purpose: Recurrent vulvovaginal candidiasis (RVVC) is one of the most common gynecological conditions in healthy and diabetic women, as well as antibiotic users. The present study was conducted to determine the relationship between TUP1 gene expression patterns and symptomatic recurrent C. albicans infections. Materials and Methods: This research was performed on C. albicans samples isolated from the vaginal specimens obtained from 31 individuals with RVVC in 2016. The reference strain C. albicans ATCC 10231, 10 C. albicans strains isolated from minimally symptomatic patients, and 10 isolates from asymptomatic patients were also used as control strains. The relative mRNA expression of the TUP1 gene was quantified using quantitative real-time polymerase chain reaction (QRT-PCR). Results: The QRT-PCR results revealed that TUP1 mRNA expression was significantly decreased (0.001-0.930 fold) in the C. albicans isolates obtained from RVVC patients (P Conclusion: The present results were suggestive of the probable contribution of TUP1, as a part of the transcriptional repressor, to the severity of the symptoms related to C. albicans infections in the vagina. Regarding this, it is required to perform more in vivo studies using a larger sample size to characterize the regulatory or stimulatory function of TUP1 in the severity of RVVC symptoms. Furthermore, the study and identification of the genes involved in the severity of the symptomatic manifestations of C. albicans, especially in resistant strains, may lead to the recognition of an alternative antifungal target to enable the development of an effective agent.

Introduction and aim: Electrocardiography is one of the most useful and common tools for examining heart function. In studies in the 1960s, heart rate variability (HRV) was introduced and used as a non-invasive tool to evaluate the functions of the autonomic nervous system and other functional disorders of the heart under various conditions. In addition to the clinical applications of heart rate variability, this physiological parameter is also widely used in ergonomics and occupational health. In the study of mental workload, exposure to industrial noise, shift work, stress, and other parameters related to the workplace benefit heart rate variability. Heart rate variability is regulated by the autonomic nervous system and by the sinoatrial (SA) node. The autonomic nervous system is divided into sympathetic and parasympathetic branches, the autonomic nervous system is divided into sympathetic and parasympathetic branches, thereby affecting the heart rate and heart rate variability. Sympathetic activity tends to increase heart rate and decrease heart rate variability, while parasympathetic tend to reduce heart rate and increase heart rate variability. The most prominent component of the variable heart rate period is a respiratory arrhythmia (RSA), which is considered to be 0.15 to 0.4 Hz. The high-frequency component is only affected by parasympathetic neural activity. Another component of heart rate variability is the low-frequency (LF) component in the frequency range, 0.04 to 0.15 Hz. This component is affected by sympathetic and parasympathetic neural activity. Many computational methods have been developed for HRV analysis, each of which is associated with strengths and weaknesses. Although there may still be difficulties in interpreting this index, it provides researchers and health experts with reliable non-invasive physiological information. HRV parameters can be classified in terms of time, frequency, and nonlinear methods. The commercially available ECG equipment does not usually include HRV features due to the lack of standard diagnostic protocols. As an alternative to this commercial software, many simple, online and free, device-independent, and portable software has been developed for HRV analysis and cardiovascular research. Heart Rate Variability Quantification: Heart rate variability can be measured in long-term (24 hours), short-term (5 minutes), and very short-term periods (less than 5 minutes) and can be analyzed as time- -domain, frequency-domain, and non-linear. 1. Time-domain measures The simplest method to analyze heart rate variability is time-domain. Analysis of heart rate variability in the time-domain is performed through both statistical and geometric analysis, both of which are based on heart rate or RR intervals between successive QRS series. Using these methods, the heart rate can be assessed at any point in time or between normal consecutive sets. Statistical parameters recommended by the European Society of Cardiology and the American Society of Pacing Electrophysiology include: 1) SDNN 2) NN50 3) SDSD 4) SDANN 5) RMSSD 6) SDSD 7) NN50 count (Table 1). Table 1: time-domain measures of HRV Variable Units Description [1]SDNN ms Standard deviation of all NN intervals SDRR[2] ms standard deviation of RR interval series SDANN ms Standard deviation of the averages of NN intervals in all 5 min segments of the entire recording SDNN index ms Mean of the standard deviations of all NN intervals for all 5 min segments of the entire recording pNN50 % NN50 count divided by the total number of all NN intervals HR Max –HR Min bmp The average difference between the highest and lowest HRs during each respiratory cycle rMSSD ms Root mean square of successive RR interval difference HRV triangular index Integral of the density of the RR interval histogram divided by its height TINN ms Baseline width of the RR interval histogram 2. Frequency-domain measures: Time-domain measurements information about the overall change in time series or maximum variable amplitude, but no information about periodic heart rate fluctuations. Data frequency domain analysis provides information on how power distribution is a function of frequency. According to the European Society of Cardiology, the power range of a healthy person is usually divided into four main frequency bands. The range of components used is usually: high-frequency (0.4 - 0.15 Hz), low-frequency (0.15-0.04 Hz), very low frequency (0.04 - 0.003 Hz) and infinitely low frequency (

Mubashra Zehra,1 Waliya Zubairi,2 Anwarul Hasan,3,4 Hira Butt,1 Amna Ramzan,1 Maryam Azam,2 Azra Mehmood,1 Mojtaba Falahati,5 Aqif Anwar Chaudhry,2 Ihtesham Ur Rehman,6 Muhammad Yar2 1National Center of Excellence in Molecular Biology (CEMB), University of the Punjab, Lahore 53700, Pakistan; 2Interdisciplinary Research Centre in Biomedical Materials, COMSATS University Islamabad, Lahore Campus, Lahore 54000, Pakistan; 3Department of Mechanical and Industrial Engineering, College of Engineering, Qatar University, Doha 2713, Qatar; 4Biomedical Research Center, Qatar University, Doha 2713, Qatar; 5Department of Nanotechnology, Faculty of Advanced Sciences and Technology, Pharmaceutical Sciences Branch, Islamic Azad University, Tehran, Iran; 6Engineering Department, Faculty of Science and Technology, Lancaster University, Lancaster LA1 4YW, UKCorrespondence: Anwarul Hasan; Muhammad Yar Tel +974-70569169; +92 42 001007 Ext 828Email ahasan@qu.edu.qa; drmyar@cuilahore.edu.pkIntroduction: Diabetic wounds are challenging to treat due to a wide range of pathophysiological changes. Hypoxia is one of the predominant contributing factors of poor vascularization and chronicity in diabetic wounds. This study was designed to develop polycaprolactone (PCL)-based oxygen-releasing electrospun wound dressings and evaluate their efficacy for improved full thickness wound healing in diabetic rats.Methods: PCL-based oxygen releasing wound dressings were made using electrospinning technology. The developed dressings were characterized in terms of physical as well as biological properties both in vitro and in vivo. E-spun nanofibrous dressings were physically characterized with scanning electron microscopy, Fourier-transform infrared spectroscopy, and Energy-dispersive X-ray spectroscopy. To study the likely impact of the fabricated wound dressings in hypoxic conditions, HIF-1α expression analysis was carried out both at gene and protein levels. Wound dressings were further evaluated for their healing potential for extensive wounds in diabetic rat models.Results: The experimental results showed that the developed dressings were capable of continuously generating oxygen for up to 10 days. Cell studies further confirmed pronounced expression of HIF-1α at gene and protein levels in cells seeded on PCL-sodium percarbonate (SPC) and PCL scaffolds compared with the cells cultured on a tissue culture plate. Chorioallantoic membrane assay revealed the supportive role of oxygen releasing dressings on angiogenesis compared to the control group. Histological assessment of the regenerated skin tissues proved that full thickness wounds covered with SPC loaded PCL dressings had a comparatively better vascularized and compact extracellular matrix with completely covered thick epithelium.Discussion: The developed oxygen generating polymeric nanofibrous wound dressings could potentially be used as an envisioned approach for the efficient recovery of chronic diabetic wounds.Keywords: skin regeneration, diabetic wound healing, oxygenation, polymeric nanofibers, electrospinning

Introduction: Dyslexia is a combination of problems that affect the learning process in one or more areas, including reading, writing, and spelling and may be associated with problems with processing speed, memory, visual-auditory perception, motor skills, and speech. Skills like comprehension and distinction of letters and sounds, communication between phonograph and writing, naming and representing letters, memory, movements, and visual and cognitive factors are concomitantly involved in this complex cognitive process. The aim of this study is to review the research available on the effectiveness of convergence, accommodative facility, and saccades on reading failure.Materials and Methods: The articles concerning dyslexia, reading disorder, phonological processing, effectiveness of convergence, saccade, and accommodative facility published between 2010 and 2020 at Google Scholar, Pubmed, and ScienceDirect databases, as well as in Persian dissertations and journals indexed in Scientific Information Database (SID) and Magiran. “Reading disorder, Dyslexia, Convergence, Accommodative facility, Saccade, Visual function, Visual perception, Visual processing, Adaptive effectiveness, Phonology recognition”, and their combinations according to Medical Subject Headings (MeSH) were used as the main keywords. The results of 18 articles were analyzed in the present study.Results: There was a significant relationship between the disorder of accommodative facility and eye movements, saccade, and dyslexdia, in a way that improving visual interventions, visual and motor perception skills, rehabilitation of basic visual functions, and saccades enhanced the accommodative facility of visual functions and reading function of students. In other words, to prevent problems or poor performance of children and students with dyslexia, more attention should be paid to these skills.Conclusion: It seems that processing of the vision perception plays an important role in reading impairment, and people who have received convergence exercises, accommodative facility, and saccade movements, including training in visual-motor perception skills, perform better in reading.

Pterocephalus (Caprifoliaceae) consists of 30 species worldwide, mainly distributed in the temperate regions of the northern hemisphere, of which 14 species were reported from Iran, including five endemic ones. In this study, 35 leaf-related traits and 30 peduncle-related traits were investigated by light microscopy of 15 samples from 11 Iranian species of Ptreocephalus. Our results showed that there were two types of midrib, six types of leaf indumentum and five types of peduncle indumentum. Crystalized calcium oxalate was observed in the leaves and peduncles of most species except in P. plumosus and P. brevis. The profiles of the peduncles were hexagonal, circular or elliptical. The vascular cylinder shape varied from circular to sinuate form. P. wendelboi, with a very different morphology as compared with other species, also exhibited different anatomical characters. The hexagonal sections of peduncle in P. ghahremanii and P. kurdicus and two samples of P. szovitsii were found to be very similar. However, the mentioned characters were found to be less informative or charachterisation of other species. In conclusion, the results showed that the anatomical characters of the leaves and peduncles might have some taxonomic importance in the identification of some species of the genus Pterocephalus.

Background & aim: Lack of objective expression of emotions leads to the experience of unpleasant thoughts and evocations, followed by the non-recognition of one’s emotions and feelings. This is identified as one of the most important factors accounting for marital conflicts. The purpose of this study was to predict marital burnout based on negative automatic thoughts and alexithymia among couples in Shiraz, Iran. Methods: This correlational study was conducted on 150 couples referring to four counseling centers located in districts 1 and 2 of Shiraz in 2018-2019. The study population was selected using a multistage cluster sampling method. The data were collected using the burnout measure developed by Pines, automatic negative thoughts questionnaire, and twenty-item Toronto alexithymia scale on a self-report basis. Data analysis was performed in SPSS software (version 21) using regression analysis and Pearson correlation coefficient at a significance level of ≤ 0.05. Results: The results showed that the dimensions of an automatic negative thoughts could predict marital burnout positively and significantly (P≤0.05). The coefficient was obtained as 0.27, meaning that automatic negative thoughts, alexithymia, age, and education could predict marital burnout at 27%. Conclusion: Alexithymia and automatic negative thoughts could eventually lead to the elevation of dissatisfaction with marriage due to exerting a negative effect on maintaining a strong emotional relationship between partners.

Abstract Background Midwifery is an emotionally challenging profession, and academic education of midwifery especially clinical learning has its own specific challenges. Midwifery students face with stressful experiences, especially related to instructor and characteristics of clinical environment, which can affect their theoretical and practical abilities. There is insufficient evidence in this field. This study aimed to explore (1) the perceived stress and stressors of midwifery students and (2) the relationships between students’ stress and related factors in clinical learning environment. Methods A cross sectional, survey design was conducted at one university in Iran. A sample of 108 students was selected using Krejcie and Morgan table in 2016. Data was collected using Persian version of Cohen’s perceived stress scale, Persian questionnaire of sources of stress and demographic form. Data was analyzed using independent t, ANOVA and correlation coefficient test (α

Aims: Happiness is one of the most important mental needs of mankind which has a major impact on personality and mental health. The aim of this study was to investigate the effectiveness of acceptance and commitment therapy and Logotherapy on happiness of veteranschr('39') spouses. Materials & Methods: In this semi experimental study with pretest-posttest design, with two case groups and one witness group, 60 people of veteranschr('39') spouses were studied in Tehran in 2017. The subjects were selected using simple random sampling method and were randomly assigned into acceptance and commitment therapy, Logotherapy and witness group (n=20 in each group). Case groups were treated in 9 sessions in 120 minutes and the witness group received no cure. The research tools were a demographic questionnaire and oxford happiness questionnaire. Data were analyzed using SPSS 18 software, through one-way analysis of covariance and Tukeychr('39')s post hoc test. Finding: By controlling the effects of pretest scores, there was a significant difference between the mean scores of happiness of the groups in the posttest step (F=10.827; p0.05). Conclusion: Both acceptance and commitment therapy and Logotherapy are effective in increasing the happiness of veteranschr('39') spouses.

Abstract Background Cerebral cavernous malformations (CCMs), a major neurosurgical condition, characterized by abnormally dilated intracranial capillaries, result in increased susceptibility to stroke. KRIT1 (CCM1), MGC4607 (CCM2), and PDCD10 (CCM3) have been identified as causes of CCMs in which at least one of them is disrupted in most familial cases. Our goal is to identify potential biomarkers and genetic modifiers of CCMs, using a global comparative omics approach across several in vitro studies and multiple in vivo animal models. We hypothesize that through analysis of the CSC utilizing various omics, we can identify potential biomarkers and genetic modifiers, by systemically evaluating effectors and binding partners of the CSC as well as second layer interactors. Methods We utilize a comparative omics approach analyzing multiple CCMs deficient animal models across nine independent studies at the genomic, transcriptomic, and proteomic levels to dissect alterations in various signaling cascades. Results Our analysis revealed a large set of genes that were validated across multiple independent studies, suggesting an important role for these identified genes in CCM pathogenesis. Conclusion This is currently one of the largest comparative omics analysis of CCM deficiencies across multiple models, allowing us to investigate global alterations among multiple signaling cascades involved in both angiogenic and non-angiogenic events and to also identify potential biomarker candidates of CCMs, which can be used for new therapeutic strategies.

Despite the promising medicinal properties, berberine (BBR), due to its relatively poor solubility in plasma, low bio-stability and limited bioavailability is not used broadly in clinical stages. Due to these drawbacks, drug delivery systems (DDSs) based on nanoscale natural polysaccharides, are applied to address these concerns. Natural polymers are biodegradable, non-immunogenic, biocompatible, and non-toxic agents that are capable of trapping large amounts of hydrophobic compounds in relatively small volumes. The use of nanoscale natural polysaccharide improves the stability and pharmacokinetics of the small molecules and, consequently, increases the therapeutic effects and reduces the side effects of the small molecules. Therefore, this paper presents an overview of the different methods used for increasing the BBR solubility and bioavailability. Afterwards, the pharmacodynamic and pharmacokinetic of BBR nanostructures were discussed followed by the introduction of natural polysaccharides of plant (cyclodextrines, glucomannan), the shells of crustaceans (chitosan), and the cell wall of brown marine algae (alginate)-based origins used to improve the dissolution rate of poorly soluble BBR and their anticancer and antibacterial properties. Finally, the anticancer and antibacterial mechanisms of free BBR and BBR nanostructures were surveyed. In conclusion, this review may pave the way for providing some useful data in the development of BBR-based platforms for clinical applications.

Thyroid cancer (TC) is the most prevalent malignancy of the endocrine system. Although there are few treatment choices for individuals with TC, determining the underlying mechanisms is essential for treatment due to the complex carcinogenesis of this disease. Recent pieces of evidence suggest that non-coding RNAs (ncRNAs) play an important role in the progression of TC. Nevertheless, the role and function of the complex regulatory interactions between multiple types of ncRNAs in the growth of this malignancy remains unknown. Competing endogenous RNA (ceRNA) is a recently found mechanism that suggests regulatory interactions between various RNAs. It has been proposed that some ncRNAs, such as long noncoding RNAs (lncRNAs), pseudogenes and circular RNAs (circRNAs), can share microRNA (miRNA) response elements, which may influence miRNA interaction with target RNAs and by doing so modulate gene expression at the transcriptional level. According to the analysis of relevant literature, numerous ceRNA networks are deregulated during TC development, metastasis, migration, invasion, epithelial-mesenchymal transition (EMT), and drug resistance. As a result, learning more about these deregulations could lead to earlier diagnosis of TC patients and the discovery of effective therapeutic targets. In this review we outline the current body of information regarding the essential roles of ceRNA networks and highlight the emerging roles of some newfound ceRNA members in different TC hallmarks.

The advancement in early diagnosis and precise treatments options result in more predictable and powerful health care modalities. Aptamers are known as nucleic acid structures with three-dimensional conformation to selectively bind a target site. Physicochemical properties of aptamers, their conjugation with nanoparticles (NPs) in theranostics applications and their internalization have been found to be of interest in development of aptamer-based drug delivery systems. Therefore, we aimed to present an overview on the structure and generation of aptamers followed by advantages of aptamers-conjugated NPs and their theranostics applications in various diseases such as oncology, inflammatory diseases and viral diseases. Afterward, we discussed several reports on the internalization approaches of aptamers, efficiency of aptamers vs. their analogous, and implications of aptamers in clinical trials. Finally, we discussed the current challenges and future perspectives of actively targeted aptamers for clinical application. In conclusion, this review may hold a great promise for development of aptamer-based therapeutic platforms in clinical trials.

Background: The role of the hematologic indicators in the identification of severe or critical patients requires further investigation. In this study, we focused on predicting Covid-19 patients at risk of progression using blood parameters. Materials and Methods: We performed a retrospective study including 444 patients with confirmed Covid-19. Hematological parameters were evaluated. The logistic regression analysis was performed with step-wise method with dependent variables such as intensive care units admission, partial pressure of oxygen saturation, and mortality. Also, independent variables such as hematological parameters, age and sex to assess variables that are likely to predict patients at risk of progression. Results: Patients in intensive care units had significantly higher mean absolute neutrophil count than outpatients (P < 0.001). There was a statistically significant difference in the mean absolute lymphocyte count between dead and survived patients (P = 0.015). Multivariate analysis confirmed the positive association of the white blood cells (P < 0.001), absolute neutrophil count (P < 0.004), red cell distribution width (P < 0.001), and lactate dehydrogenase (P = 0.007) to be positively associated with the admission of Covid-19 patients in the intensive care units and the absolute monocyte count (P = 0.012, Odds ratios = 0.100, CI95% = 0.066-0.605) to be negatively associated with mortality. Conclusion: Based on the results of our study, it is recommended to use hematological data to make clinical decisions and evaluate the patient's prognosis.

Obviously, development is the outcome of culture, and the consideration of a developed society is impossible if its culture does not support development. Culture plays an important role in companies' competitiveness and productivity through shaping the organizational behavior pattern and norms. On the other hand, the level of country or region development depends on the competitiveness of its companies, especially small and medium sized enterprises (SMEs). The purpose of this study is to investigate the cultural reasons of small share of Iranian SMEs in the market and their low competitiveness and productivity. Therefore, relationship between the productivity of active SMEs in Yazd textile industry and their employers’ culture was explored using Edgar Shine's "clinical approach" (2004) and Sariolghalam theory (2003). Pearson correlation test showed that there is not a statistically significant relationship between the productivity of these SMEs and their employers' culture. However, employers' interviews revealed that Lack of economic stability, prevalent smuggling of textile products, promotion of anti-employer mentality and misguided policies have an adverse effect on the behavior of customers and suppliers and render it impossible for the employer to make forecasts and calculations for running and developing the business.

The coronavirus disease (COVID-19) pandemic is caused by a novel coronavirus (CoV) named severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). As the angiotensin converting enzyme 2 (ACE2) is the cellular receptor of SARS-CoV-2, it has a strong interaction with the renin angiotensin system (RAS). Experimental studies have shown that the higher levels of ACE2 or increasing ACE2/ACE1 ratio improve COVID-19 outcomes through lowering inflammation and death. Aerobic moderate intensity physical exercise fights off infections by two mechanisms, the inhibition of ACE/Ang II/AT1-R pathway and the stimulation of ACE2/Ang-(1–7)/MasR axis. Exercise can also activate the anti-inflammatory response so that it can be a potential therapeutic strategy against COVID-19. Here, we summarize and focus the relation among COVID-19, RAS, and immune system and describe the potential effect of aerobic moderate intensity physical exercise against CoV as a useful complementary tool for providing immune protection against SARS-CoV-2 virus infection, which is a novel intervention that requires further investigation.

The collagen-integrin interactions are mediated by the doubly charged Mg2+ cation. In nature this cation seems to have the optimal binding strength to stabilize this complex. It is essential that the binding is not too weak so that the complex becomes unstable, however, it is also of importance that the ligand-receptor binding is still labile enough so that the ligand can separate from the receptor in a suited environment. In the case of crystal growing for experimentally useful integrin-collagen fragment complexes it turned out that Co2+ cations are ideal mediators to form stable complexes for such experiments. Although, one can argue that Co2+ is in this context an artificial cation, however, it is now of special interest to test the impact of this cation in cell-culture experiments focusing on integrin-ligand interactions. In order to examine, in particular, the role cobalt ions we have studied a Co2+ based model system using quantum chemical calculations. Thereby, we have shown that hybrid and long-range corrected functional, which are approximations provide already a sufficient level of accuracy. It is of interest to study a potential impact of cations on the binding of collagen-fragments including collagens from various species because different integrins have numerous biological functions (e.g. Integrin – NCAM (Neural cell adhesion molecule) interactions) and are triggered by intact and degraded collagen fragments. Since integrin–carbohydrate interactions play a key role when bio-medical problems such as tumor cell adhesion and virus-host cell infections have to be addressed on a sub-molecular level it is essential to understand the interactions with heavy-metal ions also at the sub-atomic level. Our findings open new routes, especially, in the fields of tissue repair and neuro-oncology for example for cell-culture experiments with different ions. Since Co2+ ions seem to bind stronger to integrin than Mg2+ ions it should be feasible to exchange these cations in suited tumor tissues although different cations are present in other metalloproteins which are active in such tissues. Various staining methods can be applied to document the interactions of integrins with carbohydrate chains and other target structures. Thereby, it is possible to study a potential impact of these interactions on biological functions. It was therefore necessary to figure out first which histological–glycobiological experimental settings of tumor cells are suited for our purpose. Since the interactions of several metalloproteins (integrin, ADAM12) with polysialic acid and the HNK-1 epitope play a crucial role in tumor tissues selected staining methods are proper tools to obtain essential information about the impact of the metal ions under study.

The aim of this study was to investigate the mechanism of interaction between quercetin-3-O-sophoroside and different SARS-CoV-2’s proteins which can bring some useful details about the control of different variants of coronavirus including the recent case, Delta. The chemical structure of the quercetin-3-O-sophoroside was first optimized. Docking studies were performed by CoV disease-2019 (COVID-19) Docking Server. Afterwards, the molecular dynamic study was done using High Throughput Molecular Dynamics (HTMD) tool. The results showed a remarkable stability of the quercetin-3-O-sophoroside based on the calculated parameters. Docking outcomes revealed that the highest affinity of quercetin-3-O-sophoroside was related to the RdRp with RNA. Molecular dynamic studies showed that the target E protein tends to be destabilized in the presence of quercetin-3-O-sophoroside. Based on these results, quercetin-3-O-sophoroside can show promising inhibitory effects on the binding site of the different receptors and may be considered as effective inhibitor of the entry and proliferation of the SARS-CoV-2 and its different variants. Finally, it should be noted, although this paper does not directly deal with the exploring the interaction of main proteins of SARS-CoV-2 Delta variant with quercetin-3-O-sophoroside, at the time of writing, no direct theoretical investigation was reported on the interaction of ligands with the main proteins of Delta variant. Therefore, the present data may provide useful information for designing some theoretical studies in the future for studying the control of SARS-CoV-2 variants due to possible structural similarity between proteins of different variants.

Tumor treating fields (TTFields) are among clinically active anticancer modalities that utilize low‐intensity, intermediate frequency (IF), and alternating electric fields (AEFs) to selectively disrupt mitosis in cancerous cells. Application of TTFields in the range of 100–900 kHz in cancer therapy and its effect on normal and cancer cells have attracted a great deal of interest in recent years. TTFields affect solid tumors by introducing increased chromatid aberrations that reduce the capacity to repair DNA damage and chromosome segregation, resulting in autophagy and subsequent cell death. In this review, we present an overview of the applications of TTFields in the treatment of cancer. We discuss several practical applications of TTField frequencies combined with metallic nanoparticles (NPs) (magnetic or nonmagnetic NPs) for internalization into cancer cells. In addition, TTFields can be combined effectively with chemotherapy and radiotherapy.

BackgroundFew data exist on the use of text messaging as a tool to promote retention in HIV care and virologic suppression at the clinic level in the United States. We describe the protocol for a study designed to investigate whether a text messaging intervention that supports healthy behaviors, encourages consistent engagement with care, and promotes antiretroviral persistence can improve retention in care and virologic suppression among patients in an urban safety-net HIV clinic in San Francisco.Methods/designConnect4Care (C4C) is a single-site, randomized year-long study of text message appointment reminders vs. text message appointment reminders plus thrice-weekly supportive, informational, and motivational text messages. Eligible consenting patients are allocated 1:1 to the two arms within strata defined by HIV diagnosis within the past 12 months (i.e. "newly diagnosed") vs. earlier. Study participants must receive primary care at the San Francisco General Hospital HIV clinic, speak English, possess a cell phone and be willing to send/receive up to 25 text messages per month, a have viral load >200 copies/μL, and be either new to the clinic or have a history of poor retention. The primary efficacy outcome is virologic suppression at 12 months and the key secondary outcome, which will also be examined as a mediator of the primary outcome, is retention in HIV care, as operationalized by kept and missed primary care visits. Process outcomes include text message response rate and percent of time in study without cell phone service. Generalized estimating equation log-binomial models will be used for intent to treat, per protocol, and mediation analyses. An assessment of the cost and cost-effectiveness of the intervention is planned along with a qualitative evaluation of the intervention.DiscussionFindings from this study will provide valuable information about the use of behavioral-theory based text messaging to promote retention in HIV care and virologic suppression, further elucidate the challenges of using texting technology with marginalized urban populations, and help guide the development of new mobile health strategies to improve HIV care cascade outcomes.Trial registrationNCT01917994.

Uterine leiomyosarcoma (uLMS) is the most frequent subtype of uterine sarcoma that presents a poor prognosis, high rates of recurrence, and metastasis. Currently, the molecular mechanism of the origin and development of uLMS is unknown. Class I histone deacetylases (including HDAC1, 2, 3, and 8) are one of the major classes of the HDAC family and catalyze the removal of acetyl groups from lysine residues in histones and cellular proteins. Class I HDACs exhibit distinct cellular and subcellular expression patterns and are involved in many biological processes and diseases through diverse signaling pathways. However, the link between class I HDACs and uLMS is still being determined. In this study, we assessed the expression panel of Class I HDACs in uLMS and characterized the role and mechanism of class I HDACs in the pathogenesis of uLMS. Immunohistochemistry analysis revealed that HDAC1, 2, and 3 are aberrantly upregulated in uLMS tissues compared to adjacent myometrium. Immunoblot analysis demonstrated that the expression levels of HDAC 1, 2, and 3 exhibited a graded increase from normal and benign to malignant uterine tumor cells. Furthermore, inhibition of HDACs with Class I HDACs inhibitor (Tucidinostat) decreased the uLMS proliferation in a dose-dependent manner. Notably, gene set enrichment analysis of differentially expressed genes (DEGs) revealed that inhibition of HDACs with Tucidinostat altered several critical pathways. Moreover, multiple epigenetic analyses suggested that Tucidinostat may alter the transcriptome via reprogramming the oncogenic epigenome and inducing the changes in microRNA-target interaction in uLMS cells. In the parallel study, we also determined the effect of DL-sulforaphane on the uLMS. Our study demonstrated the relevance of class I HDACs proteins in the pathogenesis of malignant uLMS. Further understanding the role and mechanism of HDACs in uLMS may provide a promising and novel strategy for treating patients with this aggressive uterine cancer.

At the Nanomedicine Innovation Center (NICE) at the Erasmus MC in Rotterdam, we have approached the treatment of cancer by starting with a vision of first establishing a platform that enables us to overcome the low levels of drugs delivered to tumors and the issue of dose-limiting toxicity. Showing that a reduction of the volume of distribution, and a lowering of toxicity and side-effects, accompanied by augmented intratumoral drug delivery, could change outcomes in patients, paved the way to target, not only localized disease, but also systemic and metastasized cancers. In particular, the detailed studies with intravital microscopy we performed at NICE provided us with the necessary insights and affected to a large extent our program on liposome-based cancer therapy. Together with our experience with the loco-regional treatment of cancer, this helped us to develop a program that focused on the subsequent aspects discussed here. We recognized that passive accumulation of nanoparticles was not as effective as previously believed and undertook to improve the local accumulation by changing the tumor pathophysiology and, in particular, the vascular permeability. We added the targeting of liposomes using vascular and tumor directed moieties, to improve cellular drug delivery. To improve payload delivery, we studied the modification of liposomes with phospholipids that help passive drug release and augment cellular accumulation. Second, and importantly, modification of liposomes was undertaken, to enable triggered drug release. The capability for modifying liposomes to respond to a trigger, and the ability to now apply an external trigger (e.g., hyperthermia) and specifically reach the tumor volume, resulted in the current smart drug delivery systems. Our experience at NICE, after a few decades of research on lipid-based nanoparticles, shows that, after the first liposomal formulation registered for clinical application in cancer therapy, further developments quickly followed, while further clinical applications lagged behind. Now we need to focus on and make the next steps towards the clinic, to fulfil the promise that is found there.