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Despite impressive progress in nanotechnology-based cancer therapy being made by in vitro research, few nanoparticles (NPs) have been translated into clinical trials. The wide gap between in vitro results and nanomedicine's clinical translation might be partly due to acidic microenvironment of cancer cells being ignored in in vitro studies. To check this hypothesis, we studied the biological impacts of two different structures of NPs on cancer cells (MDA-MB 231) at acidic (pH: 6.5) low (pH: 7) and physiological pH (pH: 7.4). We uncovered that a slight change in the pH of the cancer cell microenvironment affects the cellular uptake efficacy and toxicity mechanism of nanographene sheets and SPION@silica nanospheres. Both nanostructures exerted more substantial toxic impacts (e. g. apoptosis, necrosis, membrane disruption, and oxidative stress induction) against cancer cells at physiological pH compared to acidic niche. They also differently slowed or arrested phases of the cell cycle at different pH (S and G2/M at normal pH while G0/G1 at acidic/low pH). More specifically, cancer cells expressed higher levels of interleukins involved in cancer cell resistance at acidic pH than those incubated at physiological pH. This study revealed that a slight change in extracellular pH of cancer cells could strongly affect the therapeutic/toxic impact of nanomaterials and therefore, it should be considered in the future cancer nanomedicine research.

Cancer is the second leading cause of death in the world and the third leading cause of death in Iran. It has been proven that numerous cancer cases are caused by exposure to environmental pollutants. There is a public health concern regarding an increase in exposure to carcinogens across Iran through different sources (air, food, and water) and a lack of research to address this issue. This study aims to gather data on exposure to heavy metals, polycyclic aromatic hydrocarbons (PAHs), and pesticides and their intake routes during the implementation of a national population health survey. This is a cross-sectional study of environmental pollutants in Iran, with a stratified multi-stage random sampling method, which led to 660 nationally representative samples in 132 clusters in three sequential parts. The first will be questionnaires to obtain demographics, assets, food records, air quality, and food frequency. The second will be physical measurements, including anthropometric and body composition. The third will be lab assessments that measure 26 types of environmental pollutants (7 heavy metals, 16 PAHs, and 3 pesticides) in urine, inhaled air, and consumed food and water of the population under study using ICP-MS and GS-MS devices. The results of this study will inform policymakers and the general population regarding the level of threat and will provide evidence for the development of interventional and observatory plans on the reduction of exposures to these pollutants. It could also be used to develop local standards to control contaminants through the three exposure routes. This study protocol will obtain data needed for policymakers to set surveillance systems for these pollutants at the national and provincial level to address the public concerns regarding the contamination of food, air, and water.

Background: Non-communicable diseases (NCDs) are one of the greatest threats to public health, and have been related to poor quality dietary patterns. This study was conducted to determine the distribution of dietary risk factors in Iran. Methods: Cross-sectional data was gathered between April and November 2016 from 30,541 eligible adults (out of 31 050 individuals who were selected through systematic proportional to size cluster random sampling) living in urban and rural areas, using the WHO-based STEPs risk factor questionnaire. Low intakes of fruits, vegetables, dairy products, and fish, and high intakes of salty processed food (SPF), as well as daily intake of hydrogenated fat (HF) were considered as nutritional risk factors. Results: At the national level, 82.8% (95% CI: 82.4-83.2), 57.8% (95% CI: 57.2-58.4), 80.6% (95% CI: 80.1-81) and 90.3% (95% CI: 90-90.6) of participants of all age groups had sub-optimal intakes of fruits, vegetables, dairy products and fish, respectively. Furthermore, 12.8% (95% CI: 12.4-13.1), and 29.4% (95% CI: 28.9-29.9) of respondents had high SPF intakes and HF use, respectively. At the sub-national level, the highest distribution of suboptimal intake of fruits (97.2%; 95% CI:96-98.3), vegetables (79.2%; 95% CI: 76.3-82.1) and dairy products (92.9%; 95% CI: 91-94.7) was observed in Sistan and Baluchistan. Except for Boushehr and Hormozgan, the majority of the population of other provinces consumed fish less than twice a week. Similarly, the high intake of SPF was found mostly in the population of Yazd (23.7; 95% CI: 20.2-27.2). HF consumption was the highest in North Khorasan (64.2%; 95% CI: 60.3-68.1). Conclusion: These findings highlight the widespread distribution of dietary risk factors in Iran, which should be a priority for the people and the politicians in order to prevent NCDs.

The emergence of nanotechnology has created unprecedented hopes for addressing several unmet industrial and clinical issues, including the growing threat so‐termed “antibiotic resistance” in medicine. Over the last decade, nanotechnologies have demonstrated promising applications in the identification, discrimination, and removal of a wide range of pathogens. Here, recent insights into the field of bacterial nanotechnology are examined that can substantially improve the fundamental understanding of nanoparticle and bacteria interactions. A wide range of developed nanotechnology‐based approaches for bacterial detection and removal together with biofilm eradication are summarized. The challenging effects of nanotechnologies on beneficial bacteria in the human body and environment and the mechanisms of bacterial resistance to nanotherapeutics are also reviewed., Nanotechnologies are being used in the identification, discrimination, and removal of a wide range of pathogens. Pathogens, on the other hand, evolve over time and use different lines of defense and strategies to protect themselves against new treatments including nanotechnologies.

There is a direct association between salt intake and blood pressure (BP), one of the main risk factors for CVDs. However, yet there has been a debate that how strong is this association in people with and without hypertension. This study was conducted to evaluate the magnitude of the association between salt intake and BP in hypertensive and normotensive population among a nationally representative population. The study was conducted on a nationally representative sample of 18,635 Iranian adults aged 25 years and older who participated in the STEPS survey 2016 and provided urine sample. Salt intake was estimated through spot urine sample and Tanaka equation. Multiple linear regression model in survey data analysis was used to assess the independent effect of salt intake on BP. After adjusting for covariates, there was a significant association between salt intake and SBP in hypertensive (p

Recent studies suggest that cancer cell death accompanied by organelle dysfunction might be a promising approach for cancer therapy. The Golgi apparatus has a key role in cell function and may initiate signaling pathways to mitigate stress and, if irreparable, start apoptosis. It has been shown that Golgi disassembly and fragmentation under oxidative stress act as indicators for stress-mediated cell death pathways through cell cycle arrest in the G2/M phase. The present study shows that UV-induced reactive oxygen species (ROS) generation by Ag@ZnO nanoparticles (NPs) transform the Golgi structures from compressed perinuclear ribbons into detached vesicle-like structures distributed in the entire cytoplasm of melanoma cells. This study also demonstrates that Ag@ZnO NP-induced Golgi fragmentation cooccurs with G2 block of cell cycle progression, preventing cells from entering the mitosis phase. Additionally, the increased intracellular ROS production triggered by Ag@ZnO NPs upon UV exposure promoted autophagy. Taken together, Ag@ZnO NPs induce stress-related Golgi fragmentation and autophagy, finally leading to melanoma cell apoptosis. Intracellular oxidative stress generated by Ag@ZnO NPs upon UV irradiation may thus represent a targeted approach to induce cancer cell death through organelle destruction in melanoma cells, while fibroblast cells remained largely unaffected.

Alzheimer's disease (AD) is the most common type of neurodegenerative amyloid disorder causing progressive cognitive decline and memory loss. A considerable number of therapies for AD rely on inhibition/delay/dissociation of amyloid beta (Aβ) oligomers and fibrils. In this case, nanoparticles (NPs) demonstrated substantial effects on the Aβ fibrillation process; however, their effects on progressive cognitive decline and memory have been poorly investigated in vivo. In this study, acquisition and retention of spatial learning and memory are studied in a rat animal model of AD after intrahippocampal (IH) and intraperitoneal (IP) injections of a model NP, i.e., gold NPs (AuNPs). The outcomes revealed that the AuNPs could improve the acquisition and retention of spatial learning and memory in Aβ treated rats as indicated by decreased time (Aβ: 39.60 ± 3.23 s vs Aβ+AuNPs: 25.78 ± 2.80 s) and distance (Aβ: 917.98 ± 50.81 cm vs Aβ+AuNPs: 589.09 ± 65.96 cm) of finding the hidden platform during training days and by increased time spent in the target quadrant (Aβ: 19.40 ± 0.98 s vs Aβ+AuNPs: 29.36 ± 1.14 s) in the probe test in Morris water maze (MWM). Expression of brain-derived neurotrophic factor, BDNF, cAMP response element binding protein, CREB, and stromal interaction molecules, e.g., STIM1 and STIM2 was also increased, supporting improved neural survival. Our outcomes may pave a way for mechanistic insights toward the role of NPs on retrieval of the deteriorated behavioral functions in brain tissue after AD outbreak.

The earlier any catastrophic disease (e. g., cancer) is diagnosed, the more likely it can be treated, providing improved patient prognosis, extended survival and better quality of life. In early 2014, we revealed that various types of disease can substantially affect the composition/ profile of protein corona (i.e., a layer of biomolecules that forms at the surface of nanoparticles upon their interactions with biological fluids). Here, by combining the concepts of disease-specific protein corona and sensor array technology we developed a platform with disease detection capacity using blood plasma. Our sensor array consists of three cross-reactive liposomes, with distinct lipid composition and surface charge. Rather than detecting a specific biomarker, the sensor array provides pattern recognition of the corona protein composition adsorbed on the liposomes. As a feasibility study, sensor array validation was performed using plasma samples obtained from patients diagnosed with five different cancer types (i. e. lung cancer, glioblastoma, meningioma, myeloma, and pancreatic cancer) and a control group of healthy donors. Although no single corona composition is specific for any one cancer type, overlapping but distinct patterns of the corona composition constitutes a unique `` fingerprint'' for each type of cancer (with a high classification accuracy, i. e. 99.4%). To finally probe the capacity of this sensor array for early detection of cancers, we used cohort plasma obtained from healthy people who were subsequently diagnosed several years after plasma collection with lung, brain, and pancreatic cancers. Our results suggest that the disease-specific protein corona sensor array will not only be instrumental in the screening, detection, and identification of diseases, but may also help identify novel protein pattern markers whose role in disease development and/ or disease biology has not been appreciated so far.

Introduction To integrate and execute a proper preventive plan and reduce the risk of non-communicable diseases (NCDs), policy makers need to have access to both reliable data and a unique definition of metabolic syndrome (MetS). This study was conducted on the data collected by cross-sectional studies of WHO’s STEPwise approach to surveillance of NCD risk factors (STEPs) to estimate the national and sub-national prevalence rates of MetS in Iran in 2016. Materials and methods The prevalence of MetS was estimated among 18,414 individuals aged ≥25 years living in urban and rural areas of Iran using various definition criteria; National Cholesterol Education Program Adult Treatment Panel III 2004 (ATP III), International Diabetes Federation (IDF), American Heart Association/National Heart, Lung, and Blood Institute (AHA/NHLBI), Joint Interim Statement (JIS). Regional IDF (RIDF) and JIS (RJIS) were defined using ethnicity-specific values of waist circumference for the country. Results National prevalence rate of MetS based on ATP III, IDF, AHA/NHLBI, JIS, RIDF and RJIS criteria were 38.3% (95% CI 37.4–39.1), 43.5% (42.7–44.4), 40.9% (40.1–41.8), 47.6% (46.8–48.5), 32.0% (31.2–32.9), and 40.8% (40.0–41.7), respectively. The prevalence was higher among females, in urban residents, and those aged 65–69 years. MetS was expected to affect about 18.7, 21.3, 20.0, 23.3, 15.7, and 20.0 million Iranians, respectively, based on ATP III, IDF, AHA/NHLBI, JIS, RIDF and RJIS. The two most common components noted in this population were reduced high-density lipoprotein cholesterol (HDL-C) levels and central obesity. Conclusion High prevalence rate of MetS among Iranian adults is alarming, especially among females, urban residents, and the elderly. The JIS definition criteria is more appropriate to determine higher number of Iranians at risk of NCDs. Proper management and prevention of MetS is required to adopt multiple national plans including lifestyle modifications, medical interventions, and public education on NCDs risk factors.

Cancer is the second leading cause of death in the world and the third leading cause of death in Iran. It has been proven that numerous cancer cases are caused by exposure to environmental pollutants. There is a public health concern regarding an increase in exposure to carcinogens across Iran through different sources (air, food, and water) and a lack of research to address this issue. This study aims to gather data on exposure to heavy metals, polycyclic aromatic hydrocarbons (PAHs), and pesticides and their intake routes during the implementation of a national population health survey. This is a cross-sectional study of environmental pollutants in Iran, with a stratified multi-stage random sampling method, which led to 660 nationally representative samples in 132 clusters in three sequential parts. The first will be questionnaires to obtain demographics, assets, food records, air quality, and food frequency. The second will be physical measurements, including anthropometric and body composition. The third will be lab assessments that measure 26 types of environmental pollutants (7 heavy metals, 16 PAHs, and 3 pesticides) in urine, inhaled air, and consumed food and water of the population under study using ICP-MS and GS-MS devices. The results of this study will inform policymakers and the general population regarding the level of threat and will provide evidence for the development of interventional and observatory plans on the reduction of exposures to these pollutants. It could also be used to develop local standards to control contaminants through the three exposure routes. This study protocol will obtain data needed for policymakers to set surveillance systems for these pollutants at the national and provincial level to address the public concerns regarding the contamination of food, air, and water.

The poor healing associated with chronic wounds affects millions of people worldwide through high mortality rates and associated costs. Chronic wounds present three main problems: First, the absence of a suitable environment to facilitate cell migration, proliferation, and angiogenesis; second, bacterial infection; and third, unbalanced and prolonged inflammation. Unfortunately, current therapeutic approaches have not been able to overcome these main issues and, therefore, have limited clinical success. Over the past decade, incorporating the unique advantages of nanomedicine into wound healing approaches has yielded promising outcomes. Nanomedicine is capable of stimulating various cellular and molecular mechanisms involved in the wound microenvironment via antibacterial, anti-inflammatory, and angiogenetic effects, potentially reversing the wound microenvironment from nonhealing to healing. This review briefly discusses wound healing mechanisms and pathophysiology and then highlights recent findings regarding the opportunities and challenges of using nanomedicine in chronic wound management.

The risk of heart failure is increased in patients with atherosclerotic diseases, as coronary artery disease (CAD) and myocardial infarction are well-known as major predecessors of heart failure. Here, we review the conventional clinical approaches to address the issues with atherosclerotic plaques. We will also highlight the problem associated with current clinical approaches. We, finally, review the current nanotechnology-based progresses in prevention of atherosclerosis progress and disruption. Atherosclerosis and thrombosis, if remains undetected and untreated, are the most common cause of heart failure through stroke and cardiomyopathy. Therefore, the field urgently needs development of new techniques for robust and reliable techniques/approaches for both early detection and treatment of atherosclerosis and thrombosis. This chapter is focused on reviewing the recent development of nanomedicine in both early diagnosis and treatment of atherosclerosis and thrombosis.

Objective In Iran, there has been no national report on salt intake based on laboratory measurements so far. Therefore, this study was conducted to measure salt intake among Iranian population at the national level. Methods In stepwise approach to conduct a surveillance survey 2016, 18 624 Iranian adults (25 years old and above), as a representative sample of Iranian adult population at national and subnational levels, underwent urine sodium measurement and were included in this study. The participants were recruited through a systematic random sampling from 30 provinces of Iran. For each individual, through a computer-assisted interview, a questionnaire on lifestyle risk factors was completed, all anthropometric indices were measured, and data on sodium of spot urine sample for all individuals and 24-h urine sample for a subsample were collected. To estimate the 24-h salt intake, common equations were used. Results In total, 97.66% of the population consumed at least 5 g of salt per day. In addition, in 41.20% of the population, the level of salt intake was at least two times higher than the level recommended by the WHO for adults. The mean of salt intake among Iranian population was 9.52 g/day (95% confidence interval: 9.48-9.56). Conclusion The study showed that the consumption of salt among the Iranian population is higher than the level recommended by WHO. To reduce salt intake, it is necessary to adopt a combination of nationwide policies such as food reformulation and food labelling.

The polarization imaging technique is a powerful approach to probe microstructural and optical information of biological structures (e.g., tissue samples). Here, we have studied the polarization properties of different bacterial colonies in order to evaluate the possibility of bacterial detection and discrimination. In this regard, we have taken the backscattering Mueller matrix images of four different bacteria colonies (i.e., Escherichia coli, Lactobacillus rhamnosus, Rhodococcus erythropolis, and Staphylococcus aureus). Although the images have the potential to distinguish qualitatively different bacterial colonies, we explored more accurate and quantitative parameters criteria for discrimination of bacterial samples; more specifically, we have exploited the Mueller matrix polar decomposition (MMPD),frequency distribution histogram (FDH), and central moment analysis method. The outcomes demonstrated a superior capacity of Mueller matrix imaging, MMPD, and FDH in bacterial colonies identification and discrimination. This approach might pave the way for a reliable, efficient, and cheap way of identification of infectious diseases.

Once in biological fluids, the surface of nanoparticles (NPs) is rapidly covered with a layer of biomolecules (i.e., the "protein corona") whose composition strongly determines their biological identity, regulates interactions with biological entities including cells and the immune system, and consequently directs the biological fate and pharmacokinetics of nanoparticles. We recently introduced the concept of a "personalized protein corona" which refers to the formation of different biological identities of the exact same type of NP after being exposed to extract plasmas from individuals who have various types of diseases. As different diseases have distinct metabolomic profiles and metabolites can interact with proteins, it is legitimate to hypothesize that metabolomic profiles in plasma may have the capacity to, at least partially, drive the formation of a personalized protein corona. To test this hypothesis, we employed a multi-scale approach composed of coarse-grained (CG) and all atom (AA) molecular dynamics (MD) simulations to probe the role of glucose and cholesterol (model metabolites in diabetes and hypercholesterolemia patients) in the interaction of fibrinogen protein and polystyrene NPs. Our results revealed that glucose and cholesterol had the capacity to induce substantial changes in the binding site of fibrinogen to the surface of NPs. More specifically, the simulation results demonstrated that increasing the metabolite amount could change the profiles of fibrinogen adsorption and replacement, what is known as the Vroman effect, on the NP surface. In addition, we also found out that metabolites can substantially determine the immune triggering potency of the fibrinogen-NP complex. Our proof-of-concept outcomes further emphasize the need for the development of patient-specific NPs in a disease type-specific manner for high yielding and safe clinical applications.

Alzheimer's disease (AD) is a type of dementia that causes major issues for patients' memory, thinking, and behavior. Despite efforts to advance AD diagnostic and therapeutic tools, AD remains incurable due to its complex and multifactorial nature and lack of effective diagnostics/therapeutics. Nanoparticles (NPs) have demonstrated the potential to overcome the challenges and limitations associated with traditional diagnostics/therapeutics. Nanotechnology is now offering new tools and insights to advance our understanding of AD and eventually may offer new hope to AD patients. Here, we review the key roles of nanotechnologies in the recent literature, in both diagnostic and therapeutic aspects of AD, and discuss how these achievements may improve patient prognosis and quality of life.

It is well understood that patients with different diseases may have a variety of specific proteins (e.g., type, amount, and configuration) in their plasmas. When nanoparticles (NPs) are exposed to these plasmas, the resulting coronas may incorporate some of the disease-specific proteins. Using gold (Au) NPs with different surface properties and corona composition, we have developed a technology for the discrimination and detection of two neurodegenerative diseases, Alzheimer's disease (AD) and multiple sclerosis (MS). Applying a variety of techniques, including UV-visible spectra, colorimetric response analyses and liquid chromatography-tandem mass spectrometry, we found the corona-NP complexes, obtained from different human serums, had distinct protein composition, including some specific proteins that are known as AD and MS biomarkers. The colorimetric responses, analyzed by chemometrics and statistical methods, demonstrate promising capabilities of the technology to unambiguously identify and discriminate AD and MS. The developed colorimetric technology might enable a simple, inexpensive and rapid detection/discrimination of neurodegenerative diseases.

The adult myocardium has a limited regenerative capacity following heart injury and the lost cells are primarily replaced by fibrotic scar tissue. Suboptimal efficiency of current clinical therapies to resurrect the infarcted heart results in injured heart enlargement and remodeling to maintain its physiological functions. These remodeling processes ultimately leads to ischemic cardiomyopathy and heart failure (HF). Recent therapeutic approaches (e.g., regenerative and nanomedicine) have shown promise to prevent HF post-myocardial infarction in animal models. However, these preclinical, clinical, and technological advancements have yet to yield substantial enhancements in the survival rate and quality of life of patients with severe ischemic injuries. This could be attributed largely to the considerable gap in knowledge between clinicians and nano-bioengineers. Development of highly effective cardiac regenerative therapies requires connecting and coordinating multiple fields, including cardiology, cellular and molecular biology, biochemistry and chemistry, and mechanical and materials sciences, among others. This review is particularly intended to bridge the knowledge gap between cardiologists and regenerative nanomedicine experts. Establishing this multidisciplinary knowledge base may help pave the way for developing novel, safer, and more effective approaches that will enable the medical community to reduce morbidity and mortality in HF patients.

There is a direct association between salt intake and blood pressure (BP), one of the main risk factors for CVDs. However, yet there has been a debate that how strong is this association in people with and without hypertension. This study was conducted to evaluate the magnitude of the association between salt intake and BP in hypertensive and normotensive population among a nationally representative population.The study was conducted on a nationally representative sample of 18,635 Iranian adults aged 25 years and older who participated in the STEPS survey 2016 and provided urine sample. Salt intake was estimated through spot urine sample and Tanaka equation. Multiple linear regression model in survey data analysis was used to assess the independent effect of salt intake on BP.After adjusting for covariates, there was a significant association between salt intake and SBP in hypertensive (p 0.001) and normotensive people (p 0.001). In hypertensive people, with 1 g of increase in salt intake, the SBP and DBP increased 0.37 mmHg and 0.07 mmHg, respectively. Whereas in normotensive people, with 1 g of increase in salt intake, the SBP and DBP increased 0.26 mmHg and 0.05 mmHg, respectively. Moreover, there was a significant trend toward an increase of SBP across salt intake quartiles in both hypertensive (p 0.001) and normotensive people (p = 0.002), though the slope was steeper in hypertensive than in normotensive people.The present study demonstrated that salt intake significantly increased SBP in both hypertensive and normotensive people, though the magnitude of this increase was greater in hypertensive people as compared with normotensive people.

Bipolar disorder is a complex neuropsychiatric disorder, characterized by intermittent episodes of mania and depression. Recent studies have indicated argyrophilic grains, composed of hyperphosphorylated tau, are observable in postmortem brains of bipolar patients. It remains uncertain how tau hyperphosphorylation results in neurodegeneration upon the disease. Recent studies have demonstrated that phosphorylated tau at Thr231 exists in two distinct cis and trans conformations, in which cis pT231-tau is highly neurotoxic and acts as an early driver of tauopathy in several neurodegenerative diseases. We herein employed an in vitro model, which resembles some aspects of bipolar disorder, to study the cis p-tau mediatory role. We established GSK3β overexpressing SH-SY5Y cells and examined cell viability, cis p-tau formation, and lithium effects by immunofluorescence and flow cytometry. We found an increase in cis p-tau levels as well as viability decrease in the cell model. Furthermore, we discovered that lithium treatment inhibits cis p-tau formation, resulting in diminished cell death. We also examined BD and healthy human brain samples and detected cis p-tau in the patients' brains. Our results show that tauopathy, observed in bipolar disorder, is being mediated through cis p-tau and that a conformer could be the cause of neurodegeneration upon the disease. Our findings would suggest novel therapeutic target to fight the devastating disorder.

Aggregation of the natively unfolded protein α-synuclein (α-syn) is key to the development of Parkinson's disease (PD). Some nanoparticles (NPs) can inhibit this process and in turn be used for treatment of PD. Using simulation strategies, we show here that α-syn self-assembly is electrostatically driven. Dimerization by head-to-head monomer contact is triggered by dipole-dipole interactions and subsequently stabilized by van der Waals interactions and hydrogen bonds. Therefore, we hypothesized that charged nano-objects could interfere with this process and thus prevent α-syn fibrillation. In our simulations, positively and negatively charged graphene sheets or superparamagnetic iron oxide NPs first interacted with α-syn's N/C terminally charged residues and then with hydrophobic residues in the non-amyloid-β component (61-95) region. In the experimental setup, we demonstrated that the charged nano-objects have the capacity not only to strongly inhibit α-syn fibrillation (both nucleation and elongation) but also to disaggregate the mature fibrils. Through the α-syn fibrillation process, the charged nano-objects induced the formation of off-pathway oligomers.

Surface functionalization strategies for targeting nanoparticles (NP) to specific organs, cells, or organelles, is the foundation for new applications of nanomedicine to drug delivery and biomedical imaging. Interaction of NPs with biological media leads to the formation of a biomolecular layer at the surface of NPs so-called as "protein corona". This corona layer can shield active molecules at the surface of NPs and cause mistargeting or unintended scavenging by the liver, kidney, or spleen. To overcome this corona issue, we have designed biotin-cysteine conjugated silica NPs (biotin was employed as a targeting molecule and cysteine was used as a zwitterionic ligand) to inhibit corona-induced mistargeting and thus significantly enhance the active targeting capability of NPs in complex biological media. To probe the targeting yield of our engineered NPs, we employed both modified silicon wafer substrates with streptavidin (i.e., biotin receptor) to simulate a target and a cell-based model platform using tumor cell lines that overexpress biotin receptors. In both cases, after incubation with human plasma (thus forming a protein corona), cellular uptake/substrate attachment of the targeted NPs with zwitterionic coatings were significantly higher than the same NPs without zwitterionic coating. Our results demonstrated that NPs with a zwitterionic surface can considerably facilitate targeting yield of NPs and provide a promising new type of nanocarriers in biological applications.

Nanomedicine, the integration of nanotechnological tools in medicine demonstrated promising potential to revolutionize the diagnosis and treatment of various human health conditions. Nanoparticles (NPs) have shown much promise in diagnostics of cancer, especially since they can accommodate targeting molecules on their surface, which search for specific tumor cell receptors upon injection into the blood stream. This concentrates the NPs in the desired tumor location. Furthermore, such receptor-specific targeting may be exploited for detection of potential metastases in an early stage. Some NPs, such as superparamagnetic iron oxide NPs (SPIONs), are also compatible with magnetic resonance imaging (MRI), which makes their clinical translation and application rather easy and accessible for tumor imaging purposes. Furthermore, multifunctional and/or theranostic NPs can be used for simultaneous imaging of cancer and drug delivery. In this review article, we will specifically focus on the application of SPIONs in early detection and imaging of major cancer types. From the Clinical Editor Super-paramagnetic iron oxide nanoparticles (SPIONs) have been reported by many to be useful as an MRI contrast agent in the detection of tumors. To further enhance the tumor imaging, SPIONs can be coupled with tumor targeting motifs. In this article, the authors performed a comprehensive review on the current status of using targeted SPIONS in tumor detection and also the potential hurdles to overcome.

Nanotechnology-based approaches have shown promising potential to overcome the challenges associated with current therapeutic/diagnostic approaches and offer exciting solutions to improve the quality of life of Alzheimer's Disease (AD) patients. Unfortunately, thus far they have failed in clinical translation. These disappointing results question whether nanotechnology-based therapeutic strategies are heading in the right direction. Here, we re-consider the problems and current therapeutic approaches from new angles and suggest what might have been overlooked in advanced AD therapy.

Correction for ‘Disease-specific protein corona sensor arrays may have disease detection capacity’ by Giulio Caracciolo et al., Nanoscale Horiz., 2019, 4, 1063–1076.

Background Hypercholesterolemia is one of the modifiable risk factors for atherosclerosis and cardiovascular diseases. Prevention and treatment of hypercholesterolemia and other lipid abnormalities require reliable data regarding the current prevalence of these abnormalities in the country. Objective This study aims to determine the current prevalence, awareness, and treatment of lipid abnormalities in Iran. Methods We planned to recruit 31,050 individuals who are 18 years old and above and take blood samples from individuals who are 25 years and above as representative sample at national and provincial levels in 2016. In practice, we recruited 21,293 Iranian adult aged more than 25 years through a systematic random sampling from 30 provinces of Iran. Sociodemographic, anthropometric, and lifestyle data and history of cardiometabolic diseases were gathered. Serum total cholesterol, high-density lipoprotein-cholesterol (HDL-C), triglyceride, low-density lipoprotein-cholesterol (LDL-C), and non–HDL-C were investigated. The prevalence of lipid abnormalities, awareness, treatment, and achievement to non–HDL-C and LDL-C goals were determined based on National Cholesterol Education Program Adult Treatment Panel III criteria. Results In this representative Iranian adult population, 80.0% had at least one lipid abnormality, 69.2% had low HDL-C, 39.5% had high non–HDL-C, 28.0% had hypertriglyceridemia, and 26.7% hypercholesterolemia. Of those with hypercholesterolemia, 74.2% were aware of their lipid abnormality. Only 22.0% and 36.5% of the study population met the desired level of non–HDL-C and LDL-C, respectively. Conclusion Low HDL-C is the main lipid abnormality in adult Iranian population. The majority of the population did not meet the desired level of non–HDL-C and LDL-C. Public health preventive policies should be made and implemented to better manage dyslipidemia.

Protein unfolding induced by nanoparticles (NPs) can lead to exposure of cryptic epitopes that might dictate biological identity and affect NP biological fate (e.g., blood circulation time, biodistribution, and tumor accumulation). Here, we monitor the conformation of fluorescence resonance energy transfer (FRET)-labelled fibronectin (FN) on corona-coated gold NPs. We found that the labelled FN proteins, which directly accessed the gold NP surface, underwent more pronounced conformational changes than those associated with the protein corona via protein-protein interactions. FRET and liquid chromatography-mass spectrometry analyses demonstrated that NP size/concentration, pH change, and the level of surface coverage by the corona can tune the accessibility of labelled FN to the gold NP surface. Although some subsequently adsorbing proteins accessed the NP surface thanks to incomplete surface coverage and protein exchange (the Vroman effect), most outer-layer proteins could not directly bind to the NP surface, blocked by pre-adsorbed corona layers. This finding was also partially confirmed by isothermal titration calorimetry (ITC) analysis. These results suggest the proof-of-concept that outermost-layer proteins with modestly changed conformation rather than unfolded proteins at the gold NP surface effectively create the NPs' biological identity, which might have important implications on biological fates of gold NPs.

The hard corona, the protein shell that is strongly attached to the surface of nano-objects in biological fluids, is recognized as the first layer that interacts with biological objects (e.g., cells and tissues). The decoration of the hard corona (i.e., the type, amount, and conformation of the attached proteins) can define the biological fate of the nanomaterial. Recent developments have revealed that corona decoration strongly depends on the type of disease in human patients from which the plasma is obtained as a protein source for corona formation (referred to as the 'personalized protein corona'). In this study, we demonstrate that graphene oxide (GO) sheets can trigger different biological responses in the presence of coronas obtained from various types of diseases. GO sheets were incubated with plasma from human subjects with different diseases/conditions, including hypofibrinogenemia, blood cancer, thalassemia major, thalassemia minor, rheumatism, fauvism, hypercholesterolemia, diabetes, and pregnancy. Identical sheets coated with varying protein corona decorations exhibited significantly different cellular toxicity, apoptosis, and uptake, reactive oxygen species production, lipid peroxidation and nitrogen oxide levels. The results of this report will help researchers design efficient and safe, patient-specific nano biomaterials in a disease type-specific manner for clinical and biological applications.

Protein fibrillation process (e.g., from amyloid beta (Aβ) and α-synuclein) is the main cause of several catastrophic neurodegenerative diseases such as Alzheimer's and Parkinson diseases. During the past few decades, nanoparticles (NPs) were recognized as one of the most promising tools for inhibiting the progress of the disease by controlling the fibrillation kinetic process; for instance, gold NPs have a strong capability to inhibit Aβ fibrillations. It is now well understood that a layer of biomolecules would cover the surface of NPs (so called "protein corona") upon the interaction of NPs with protein sources. Due to the fact that the biological species (e.g., cells and amyloidal proteins) "see" the protein corona coated NPs rather than the pristine coated particles, one should monitor the fibrillation process of amyloidal proteins in the presence of corona coated NPs (and not pristine coated ones). Therefore, the previously obtained data on NPs effects on the fibrillation process should be modified to achieve a more reliable and predictable in vivo results. Herein, we probed the effects of various gold NPs (with different sizes and shapes) on the fibrillation process of Aβ in the presence and absence of protein sources (i.e., serum and plasma). We found that the protein corona formed a shell at the surface of gold NPs, regardless of their size and shape, reducing the access of Aβ to the gold inhibitory surface and, therefore, affecting the rate of Aβ fibril formation. More specifically, the anti-fibrillation potencies of various corona coated gold NPs were strongly dependent on the protein source and their concentrations (10% serum/plasma (simulation of an in vitro milieu) and 100% serum/plasma (simulation of an in vivo milieu)).

The rise in non-communicable diseases (NCDs) has gained increasing attention. There is a great need for reliable data to address such problems. Here, we describe the development of a comprehensive set of executive and scientific protocols and instructions of STEPs 2016.This is a large-scale cross-sectional study of Surveillance of Risk Factors of NCDs in Iran. Through systematic proportional to size cluster random sampling, 31,050 participants enrolled in three sequential processes, of completing questionnaires; physical measurements, and lab assessment.Out of 429 districts, samples were taken from urban and rural areas of 389 districts. After applying sampling weight to the samples, comparing the distribution of population and samples, compared classification was determined in accordance with the age and sex groups. Out of 31,050 expected participants, 30,541 participant completed questionnaires (52.31% female). For physical measurements and lab assessment, the cases included 30,042 (52.38% female) and 19,778 (54.04% female), respectively.There is an urgent need to focus on reviewing trend analyses of NCDs.To the best of our knowledge, the present study is the first comprehensive experience on systematic electronic national survey. The results could be also used for future complementary studies.

Superparamagnetic zinc ferrite spinel-graphene nanostructures were synthesized as potential therapeutic agents in the magnetic targeted photothermal therapy of cancer and/or drug delivery. The global temperature of the solution and the local temperature at the nanoparticle (NP) surface determine the protein corona composition/content, which in turn affects the biological effects of NPs and the corresponding physiological responses. Therefore, it is rational to hypothesize that spinel-graphene nanostructures may have distinct protein corona compositions and contents, and therapeutic and toxic effects under laser irradiation. To assess this hypothesis, the effects of laser irradiation on the competitive binding of proteins to the spinel-graphene surface and the corresponding therapeutic effects of corona-coated spinel-graphene nanomaterials against cancer were evaluated. The results showed that the composition and content of the protein corona adsorbed onto the spinel-graphene nanomaterials was correlated with the local and global heating caused by laser irradiation. Moreover, the corona-coated spinel-graphene nanomaterials obtained following laser irradiation induced a higher intracellular concentration of reactive oxygen species (ROS) and exhibited a significantly higher cellular uptake efficacy compared to that achieved in the absence of laser irradiation (37 °C). This finding indicates that the therapeutic effects of graphene-based photothermal therapy against cancer are, in part, related to the composition and content of the protein corona formed under laser irradiation. The results of this study reveal that changes in the composition and content of the protein corona that occur during laser irradiation affect the therapeutic and toxic effects of NPs.

EMT-type zeolite nanoparticles (EMT NPs) with particle size of 10–20 nm and external surface area of 200 m2/g have shown high selective affinity toward plasma protein (fibrinogen). Besides, the EMT NPs have demonstrated no adverse effect on blood coagulation hemostasis. Therefore, it was envisioned that the EMT NPs could inhibit possible β-amyloid (Aβ)–fibrinogen interactions that result in the formation of structurally abnormal clots, which are resistant to lysis, in cerebral vessels of patients with Alzheimer disease (AD). To evaluate this hypothesis, the clot formation and degradation of Aβ–fibrinogen in the presence and absence of the EMT zeolite NPs were assessed. The results clearly showed that the delay in clot dissolution was significantly reduced in the presence of zeolite NPs. By formation of protein corona, the EMT NPs showed a negligible reduction in their inhibitory strength. Docking of small molecules (Aβ–fibrinogen) introduced a novel potential inhibitory candidate. The zeolite NPs showed s...

Pseudomonas aeruginosa ATCC9027 is an engineered strain in Iran to reduce the energy consumption in biodesulfurization, which is capable of producing the rhamnolipid biosurfactant. The biochemical analyses demonstrated that this strain reduced surface tension from 70 to 28 mN/m and emulsified hexadecane by 60%. The highest biosurfactant production was achieved when the cells were grown in minimal salt medium containing 1% (v/v) olive oil and 0.1% (w/v) yeast extract and in the presence of Isoleusin amino acid, Mg2+ (4 mg/l) and Fe2+ (0.8 g/l). Fourier transform infrared spectroscopy indicated the presence of carboxyl, amine, hydroxyl, and methoxyl groups in the extracted biosurfactant. Finally the rhlA and rhlB genes of P. aeruginosa ATCC9027 were sequenced and were highly similar to those of other strains of P. aeruginosa.

Rhamnolipid biosurfactant plays an important role in accelerated bioremediation of hydrocarbon-contaminated sites. In this article, the in vitro effects of rhamnolipid biosurfactant on reduction of energy consumption of biodesulfurization activity were evaluated in recombinant Pseudomonas aeruginosa ATCC9027. The data obtained of these analyses showed that the amount of 2-hydroxybiphenyl production in the presence of rhamnolipid was approximately 150% higher than that produced without rhamnolipid. These analyses demonstrated that the rhamnolipid is a major cause of reduction of energy consumption in biodesulfurization of resting cells. However, the rhamnolipid had no effect in reduction of energy consumption in biodesulfurization of growing cells.

Gordonia RIPI is a novel indigenous desulfurizing bacterium with the ability of desulfurization of the fuel's energy sources, isolated soil of Iran. This gram positive bacterium is stable in fossil energy and petroleum compounds and is able to catabolize dibenzotiophene to 2-hydroxybiphenyl and sulfite. This bacterium could be a suitable candidate in reduction of energy consuming in biodesulfurization regarding our data. In this study, the dsz operon and dszD gene of this strain were isolated, sequenced, and demonstrated high conservation between these chromosomal-encoded genes and its plasmid-encoded counterpart in Rhodococcus erythroplois IGTS8. The homology of dszD gene was 98% and the homology of dszA, dszB, and dszC genes was 87.5, 88.7, and 91.1%, respectively.

The energy consumption in the biodesulfurization process was reduced by production of rhamnolipid biosurfactant in engineered biodesulfurization biocatalyst Pseudomonas aeruginosa ATCC 9027. This strain, which previously was genetically engineered for its stable biodesulfurization characteristic, was examined as having the potential to produce a type of glicolipid biosurfactant. Different environmental factors were added to examine the effects on the stability, surface tension reduction, and oil displacement of this biosurfactant. In addition, the study on the biosurfactant production time course revealed that the biosurfactant production was parallel to cell growth. However, maximum biosurfactant production occurred and was established in the stationary growth phase (after 84 h). The results demonstrated that different environmental factors, such as temperature, salinary, and aeration, barely affected the biosurfactant production and stability.

In this study, dszA,B,C genes from Rhodococcus erythropolis IGTS8 were inserted stably into the chromosome of a new indigenous bacteria (Pseudomonas putida) isolated from Iranian soil to reduce energy consuming in the biodesulfurization process. The results demonstrated that the biodesulfurization activity of recombinant P. putida is higher than that of R. erythropolis IGTS8 in the primary hours and the biodesulfurization activity of R. erythropolis increased after a long time. The engineered P. putida can be promoted to a candidate for reduction of energy consuming in the biodesulfurization process because this recombinant biocatalyst removed the highest amount of dibenzothiophen in the shortest time and is a solvent tolerant bacterium with the ability of efflux of the organic solvent, which is able to supply energy for biodesulfurization reaction.

As research progresses, nanoparticles (NPs) are becoming increasingly promising tools for medical diagnostics and therapeutics. Despite this rise, their potential risks to human health, together with environmental issues, has led to increasing concerns regarding their use. As such, a comprehensive understanding of the interactions that occur at the nano-bio interface is required in order to design safe, reliable and efficient NPs for biomedical applications. To this end, extensive studies have been dedicated to probing the factors that define various properties of the nano-bio interface. However, the literature remains unclear and contains conflicting reports on cytotoxicity and biological fates, even for seemingly identical NPs. This uncertainty reveals that we frequently fail to identify and control relevant parameters that unambiguously and reproducibly determine the toxicity of nanoparticles, both in vitro and in vivo. An effective understanding of the toxicological impact of NPs requires the consideration of relevant factors, including the temperature of the target tissue, plasma gradient, cell shape, interfacial effects and personalized protein corona. In this review, we discuss the factors that play a critical role in nano-bio interface processes and nanotoxicity. A proper combinatorial assessment of these factors substantially changes our insight into the cytotoxicity, distribution and biological fate of NPs.

Superparamagnetic iron oxide nanoparticles (SPIONs) are recognized as one of the promising nanomaterials for applications in various field of nanomedicine such as targeted imaging/drug delivery, tissue engineering, hyperthermia, and gene therapy. Besides their suitable biocompatibility, SPIONs' unique magnetic properties make them an outstanding candidate for theranostic nanomedicine. Very recent progress in the field revealed that the presence of external magnetic fields may cause considerable amount of SPIONs' agglomeration in their colloidal suspension. As variation of physicochemical properties of colloidal nanoparticles has strong effect on their biological outcomes, one can expect that the SPIONs' agglomeration in the presence of external magnetic fields could change their well-recognized biological impacts. In this case, here, we probed the cellular uptake and toxicity of the SPIONs before and after exposure to external magnetic fields. We found that the external magnetic fields can affect the biological outcome of magnetic nanoparticles.

Antibacterial agents are very important in the textile industry, water disinfection, medicine, and food packaging. Organic compounds used for disinfection have some disadvantages, including toxicity to the human body, therefore, the interest in inorganic disinfectants such as metal oxide nanoparticles (NPs) is increasing. This review focuses on the properties and applications of inorganic nanostructured materials and their surface modifications, with good antimicrobial activity. Such improved antibacterial agents locally destroy bacteria, without being toxic to the surrounding tissue. We also provide an overview of opportunities and risks of using NPs as antibacterial agents. In particular, we discuss the role of different NP materials.

The combustion of sulfur-rich fossil fuels leads to release of sulfur oxide pollution in the environment. In biodesulfurization process, an organism is able to remove sulfur from fossil fuels without decreasing the caloric value of those substrates. The main aim of this research was to design a recombinant microorganism to remove the highest amount of sulfur compounds in fossil fuels.Three genes (dszA,B,C) from dsz operon are responsible for the 4S pathway (biodesulfurization pathway) in Rhodococcus erythropolis IGTS8 were inserted into the chromosome of a novel indigenous Pseudomonas putida. The reaction catalyzed by products of dszA,B,C genes require FMNH2 supplied by dszD enzyme. Thus, pVLT31 vector harboring dszD gene was transferred into this recombinant strain.The results demonstrated a higher biodesulfurization activity when the flavin reductase gene was transferred into recombinant P. putida harboring dszA,B,C. These results were approved by the Gibbs test and HPLC analysis.These analyses showed that this novel indigenous engineered P. putida could be a promising candidate for an industrial and environmental application for Biodesulfurization process.

Figure 3, Figure 4 contained errors. The corrected figures and figure captions are shown here. The authors apologize for this error.Figure 3Schematic representation of toxicology effect of multifunctional nanoparticles (NPs) in bacterial biofilms. Monodisperse superparamagnetic iron oxide NPs (SPIONs; black spheres) are coated with silver (gray shell), gold (yellow shell), and silver ring-coated, gold-coated SPIONs; silver ring-coated SPIONs and silver ring-coated, gold-coated SPIONs have strong toxic effects on bacterial biofilms, by penetration into the biofilms. Both SPIONs cores and the intermediate gold shell have the capability to induce heat by applying alternative magnetic and laser fields, respectively; the produced heat can be used as additional means to escalate bacterial death using these NPs. The magnified section in the center illustrates the irreversible effects of NPs and their ions on the various parts of the bacteria.View Large Image | Download PowerPoint SlideFigure 4Mechanisms of toxicity of nanoparticles (NPs) against bacteria. NPs and their ions (e.g., silver and zinc) can produce free radicals, resulting in induction of oxidative stress (i.e., reactive oxygen species; ROS). The produced ROS can irreversibly damage bacteria resulting in bacterial death.View Large Image | Download PowerPoint Slide

It is now well known that the primary interactions of biological entities (e. g., tissues and cells) with nano-particles (NPs) are strongly influenced by the protein composition of the "corona" (i. e., the NP surface attached proteins). The composition of the corona strongly depends on the protein source (e. g., human plasma). Because the protein source determines the NP corona, it is reasonable to hypothesize that humans with specific disease(s) may have specific NP coronas. To test this hypothesis, we incubated two different hydrophobic/hydrophilic types of NPs (polystyrene and silica) with plasma from human subjects with different diseases and medical conditions (e. g., breast cancer, diabetes, hypercholesterolemia, rheumatism, fauvism, smoking, hemodialysis, thalassemia, hemophilia A and B, pregnancy, common cold and hypofibrinogenemia). Our results demonstrate that the type of disease has a crucial role in the protein composition of the NP corona. Based on these results, we introduce the concept of the "personalized protein corona" (PPC) as a determinant factor in nano-biomedical science. This study will help researchers rationally design experiments based on the "personalized protein corona" for clinical and biological applications.