Urmia University

<h3>Importance</h3> Cancer and other noncommunicable diseases (NCDs) are now widely recognized as a threat to global development. The latest United Nations high-level meeting on NCDs reaffirmed this observation and also highlighted the slow progress in meeting the 2011 Political Declaration on the Prevention and Control of Noncommunicable Diseases and the third Sustainable Development Goal. Lack of situational analyses, priority setting, and budgeting have been identified as major obstacles in achieving these goals. All of these have in common that they require information on the local cancer epidemiology. The Global Burden of Disease (GBD) study is uniquely poised to provide these crucial data. <h3>Objective</h3> To describe cancer burden for 29 cancer groups in 195 countries from 1990 through 2017 to provide data needed for cancer control planning. <h3>Evidence Review</h3> We used the GBD study estimation methods to describe cancer incidence, mortality, years lived with disability, years of life lost, and disability-adjusted life-years (DALYs). Results are presented at the national level as well as by Socio-demographic Index (SDI), a composite indicator of income, educational attainment, and total fertility rate. We also analyzed the influence of the epidemiological vs the demographic transition on cancer incidence. <h3>Findings</h3> In 2017, there were 24.5 million incident cancer cases worldwide (16.8 million without nonmelanoma skin cancer [NMSC]) and 9.6 million cancer deaths. The majority of cancer DALYs came from years of life lost (97%), and only 3% came from years lived with disability. The odds of developing cancer were the lowest in the low SDI quintile (1 in 7) and the highest in the high SDI quintile (1 in 2) for both sexes. In 2017, the most common incident cancers in men were NMSC (4.3 million incident cases); tracheal, bronchus, and lung (TBL) cancer (1.5 million incident cases); and prostate cancer (1.3 million incident cases). The most common causes of cancer deaths and DALYs for men were TBL cancer (1.3 million deaths and 28.4 million DALYs), liver cancer (572 000 deaths and 15.2 million DALYs), and stomach cancer (542 000 deaths and 12.2 million DALYs). For women in 2017, the most common incident cancers were NMSC (3.3 million incident cases), breast cancer (1.9 million incident cases), and colorectal cancer (819 000 incident cases). The leading causes of cancer deaths and DALYs for women were breast cancer (601 000 deaths and 17.4 million DALYs), TBL cancer (596 000 deaths and 12.6 million DALYs), and colorectal cancer (414 000 deaths and 8.3 million DALYs). <h3>Conclusions and Relevance</h3> The national epidemiological profiles of cancer burden in the GBD study show large heterogeneities, which are a reflection of different exposures to risk factors, economic settings, lifestyles, and access to care and screening. The GBD study can be used by policy makers and other stakeholders to develop and improve national and local cancer control in order to achieve the global targets and improve equity in cancer care.

BACKGROUND: One common model utilized to understand clinical staff and patients' technology adoption is the technology acceptance model (TAM). OBJECTIVE: This article reviews published research on TAM use in health information systems development and implementation with regard to application areas and model extensions after its initial introduction. METHOD: An electronic literature search supplemented by citation searching was conducted on February 2017 of the Web of Science, PubMed, and Scopus databases, yielding a total of 492 references. Upon eliminating duplicates and applying inclusion and exclusion criteria, 134 articles were retained. These articles were appraised and divided into three categories according to research topic: studies using the original TAM, studies using an extended TAM, and acceptance model comparisons including the TAM. RESULTS: The review identified three main information and communication technology (ICT) application areas for the TAM in health services: telemedicine, electronic health records, and mobile applications. The original TAM was found to have been extended to fit dynamic health service environments by integration of components from theoretical frameworks such as the theory of planned behavior and unified theory of acceptance and use of technology, as well as by adding variables in specific contextual settings. These variables frequently reflected the concepts subjective norm and self-efficacy, but also compatibility, experience, training, anxiety, habit, and facilitators were considered. CONCLUSION: Telemedicine applications were between 1999 and 2017, the ICT application area most frequently studied using the TAM, implying that acceptance of this technology was a major challenge when exploiting ICT to develop health service organizations during this period. A majority of the reviewed articles reported extensions of the original TAM, suggesting that no optimal TAM version for use in health services has been established. Although the review results indicate a continuous progress, there are still areas that can be expanded and improved to increase the predictive performance of the TAM.

Collagen and gelatin have been widely used in the food, pharmaceutical, and cosmetic industries due to their excellent biocompatibility, easy biodegradability, and weak antigenicity. Fish collagen and gelatin are of renewed interest, owing to the safety and religious concerns of their mammalian counterparts. The structure of collagen has been studied using various modern technologies, and interpretation of the raw data should be done with caution. The structure of collagen may vary with sources and seasons, which may affect its applications and optimal extraction conditions. Numerous studies have investigated the bioactivities and biological effects of collagen, gelatin, and their hydrolysis peptides, using both in vitro and in vivo assay models. In addition to their established nutritional value as a protein source, collagen and collagen-derived products may exert various potential biological activities on cells in the extracellular matrix through the corresponding food-derived peptides after ingestion, and this might justify their applications in dietary supplements and pharmaceutical preparations. Moreover, an increasing number of novel applications have been found for collagen and gelatin. Therefore, this review covers the current understanding of the structure, bioactivities, and biological effects of collagen, gelatin, and gelatin hydrolysates as well as their most recent applications.

BACKGROUND: Exosomes are progressively known as significant mediators of cell-to-cell communication. They convey active biomolecules to target cells and have vital functions in several physiological and pathological processes, and show substantial promise as novel treatment strategies for diseases. METHODS: In this review study, we studied numerous articles over the past two decades published on application of exosomes in different diseases as well as on perspective and challenges in this field. RESULTS: The main clinical application of exosomes are using them as a biomarker, cell-free therapeutic agents, drug delivery carriers, basic analysis for exosome kinetics, and cancer vaccine. Different exosomes from human or plant sources are utilized in various clinical trials. Most researchers used exosomes from the circulatory system for biomarker experiments. Mesenchymal stem cells (MSCs) and dendritic cells (DCs) are two widely held cell sources for exosome use. MSCs-derived exosomes are commonly used for inflammation treatment and drug delivery, while DCs-exosomes are used to induce inflammation response in cancer patients. However, the clinical application of exosomes faces various questions and challenges. In addition, translation of exosome-based clinical trials is required to conform to specific good manufacturing practices (GMP). In this review, we summarize exosomes in the clinical trials according to the type of application and disease. We also address the main questions and challenges regarding exosome kinetics and clinical applications. CONCLUSIONS: Exosomes are promising platforms for treatment of many diseases in clinical trials. This exciting field is developing hastily, understanding of the underlying mechanisms that direct the various observed roles of exosomes remains far from complete and needs further multidisciplinary research in working with these small vesicles. Video Abstract.

Abstract Considering titanium dioxide nanoparticles (TiO 2 NPs) role in plant growth and especially in plant tolerance against abiotic stress, a greenhouse experiment was carried out to evaluate TiO 2 NPs effects (0, 50, 100 and 200 mg L −1 ) on agronomic traits of Moldavian balm ( Dracocephalum moldavica L.) plants grown under different salinity levels (0, 50 and 100 mM NaCl). Results demonstrated that all agronomic traits were negatively affected under all salinity levels but application of 100 mg L −1 TiO 2 NPs mitigated these negative effects. TiO 2 NPs application on Moldavian balm grown under salt stress conditions improved all agronomic traits and increased antioxidant enzyme activity compared with plants grown under salinity without TiO 2 NP treatment. The application of TiO 2 NPs significantly lowered H 2 O 2 concentration. In addition, highest essential oil content (1.19%) was obtained in 100 mg L −1 TiO 2 NP-treated plants under control conditions. Comprehensive GC/MS analysis of essential oils showed that geranial, z-citral, geranyl acetate and geraniol were the dominant essential oil components. The highest amounts for geranial, geraniol and z-citral were obtained in 100 mg L −1 TiO 2 NP-treated plants under control conditions. In conclusion, application of 100 mg L −1 TiO 2 NPs could significantly ameliorate the salinity effects in Moldavian balm.

Regenerative medicine has sparked interest in potential strategies for bone repair. Bone defects are widespread and could be caused by trauma, congenital malformations, infections, and surgery. Although bone has a large self-healing capacity, some defects or fractures are too big to regenerate. To regenerate bone structures which can be used for treatment of patients, bone growth must be induced by a number of bioactive implantable materials, cell types and intracellular, and extracellular molecular signaling pathways. Since mesenchymal stem cells (MSCs) and their differentiation during remodeling processes have important roles in bone regeneration, it is believed that understanding molecular signaling pathways involved is crucial to the development of bone implants, bone substitute materials, and cell-based scaffolds for bone regeneration. In this review, we briefly introduce concepts in fracture repair and regeneration following bone injuries, and then discuss the current clinical methods in bone regeneration. In the next section, we review the involvement of the various key signaling pathways in bone regeneration.

Epithelial-mesenchymal transition (EMT) and Cancer stem-like cells (CSCs) are major factors contributing to the metastasis of cancer cells. Consequently, the signaling pathways involved in both processes are appropriate therapeutic targets in the treatment of metastasis. Autophagy is another process that has recently attracted the attention of many researchers; depending on the type of cancer and tissue and the stage of cancer, this process can play a dual role in the development of cancer cells. Studies on cancer cells have shown that different signaling pathways are involved in all three processes, namely, cancer stem cells, autophagy, and EMT. The purpose of this study was to investigate and elucidate the relationship between the effective signaling pathways in all three processes, which could play an effective role in determining appropriate therapeutic goals.

BACKGROUND: Myocardial infarction (MI) is one of the life-threatening coronary-associated pathologies characterized by sudden cardiac death. The provision of complete insight into MI complications along with designing a preventive program against MI seems necessary. METHODS: Various databases (PubMed, Web of Science, ScienceDirect, Scopus, Embase, and Google scholar search engine) were hired for comprehensive searching. The keywords of "Prevalence", "Outbreak", "Burden", "Myocardial Infarction", "Myocardial Infarct", and "Heart Attack" were hired with no time/language restrictions. Collected data were imported into the information management software (EndNote v.8x). Also, citations of all relevant articles were screened manually. The search was updated on 2022.9.13 prior to the publication. RESULTS: Twenty-two eligible studies with a sample size of 2,982,6717 individuals (< 60 years) were included for data analysis. The global prevalence of MI in individuals < 60 years was found 3.8%. Also, following the assessment of 20 eligible investigations with a sample size of 5,071,185 individuals (> 60 years), this value was detected at 9.5%. CONCLUSION: Due to the accelerated rate of MI prevalence in older ages, precise attention by patients regarding the complications of MI seems critical. Thus, determination of preventive planning along with the application of safe treatment methods is critical.

BACKGROUND: Autism spectrum disorder (ASD) is one of the serious developmental disorders that is usually diagnosed below the age of three years. Although the severity of the disease's symptoms varies from patient to patient, the ability to communicate with others is affected in all forms of ASD. This study aimed to determine the prevalence of ASD in high-risk groups by continent. METHODS: The present study was conducted by systematic review and meta-analysis from 2008 to July 2021. Databases such as Science Direct, PubMed, Scopus, SID, Magiran, Web of Science (WoS), and Google Scholar from 2008 to July 2021 were searched to find related studies. Data were analysed using Comprehensive Meta-Analysis software (Version 2). RESULTS: A total of 74 studies with 30,212,757 participants were included in this study. The prevalence of ASD in the world was 0.6% (95% confidence interval: 0.4-1%). Subgroup analyses indicated that the prevalence of ASD in Asia, America, Europe, Africa and Australia was 0.4% (95% CI: 0.1-1), 1% (95% CI: 0.8-1.1), 0.5% (95% CI: 0.2-1), 1% (95% CI: 0.3-3.1), 1.7% (95% CI: 0.5-6.1) respectively. CONCLUSION: ASD imposes a heavy health burden on communities around the world. Early detection of ASD can reduce the incidence of developmental disorders and improve patients' communication skills. Therefore, health policymakers need to be aware of the prevalence and increasing trend of ASD to implement appropriate planning and interventions to reduce its consequences.

Mesenchymal stem cells (MSCs) have captured great attention in regenerative medicine for over a few decades by virtue of their differentiation capacity, potent immunomodulatory properties, and their ability to be favorably cultured and manipulated. Recent investigations implied that the pleiotropic effects of MSCs is not associated to their ability of differentiation, but rather is mediated by the secretion of soluble paracrine factors. Exosomes, nanoscale extracellular vesicles, are one of these paracrine mediators. Exosomes transfer functional cargos like miRNA and mRNA molecules, peptides, proteins, cytokines and lipids from MSCs to the recipient cells. Exosomes participate in intercellular communication events and contribute to the healing of injured or diseased tissues and organs. Studies reported that exosomes alone are responsible for the therapeutic effects of MSCs in numerous experimental models. Therefore, MSC-derived exosomes can be manipulated and applied to establish a novel cell-free therapeutic approach for treatment of a variety of diseases including heart, kidney, liver, immune and neurological diseases, and cutaneous wound healing. In comparison with their donor cells, MSC-derived exosomes offer more stable entities and diminished safety risks regarding the administration of live cells, e.g. microvasculature occlusion risk. This review discusses the exosome isolation methods invented and utilized in the clinical setting thus far and presents a summary of current information on MSC exosomes in translational medicine.

BACKGROUND: For more than three decades, the Global Burden of Diseases, Injuries, and Risk Factors Study (GBD) has provided a framework to quantify health loss due to diseases, injuries, and associated risk factors. This paper presents GBD 2023 findings on disease and injury burden and risk-attributable health loss, offering a global audit of the state of world health to inform public health priorities. This work captures the evolving landscape of health metrics across age groups, sexes, and locations, while reflecting on the remaining post-COVID-19 challenges to achieving our collective global health ambitions. METHODS: The GBD 2023 combined analysis estimated years lived with disability (YLDs), years of life lost (YLLs), and disability-adjusted life-years (DALYs) for 375 diseases and injuries, and risk-attributable burden associated with 88 modifiable risk factors. Of the more than 310 000 total data sources used for all GBD 2023 (about 30% of which were new to this estimation round), more than 120 000 sources were used for estimation of disease and injury burden and 59 000 for risk factor estimation, and included vital registration systems, surveys, disease registries, and published scientific literature. Data were analysed using previously established modelling approaches, such as disease modelling meta-regression version 2.1 (DisMod-MR 2.1) and comparative risk assessment methods. Diseases and injuries were categorised into four levels on the basis of the established GBD cause hierarchy, as were risk factors using the GBD risk hierarchy. Estimates stratified by age, sex, location, and year from 1990 to 2023 were focused on disease-specific time trends over the 2010-23 period and presented as counts (to three significant figures) and age-standardised rates per 100 000 person-years (to one decimal place). For each measure, 95% uncertainty intervals [UIs] were calculated with the 2·5th and 97·5th percentile ordered values from a 250-draw distribution. FINDINGS: Total numbers of global DALYs grew 6·1% (95% UI 4·0-8·1), from 2·64 billion (2·46-2·86) in 2010 to 2·80 billion (2·57-3·08) in 2023, but age-standardised DALY rates, which account for population growth and ageing, decreased by 12·6% (11·0-14·1), revealing large long-term health improvements. Non-communicable diseases (NCDs) contributed 1·45 billion (1·31-1·61) global DALYs in 2010, increasing to 1·80 billion (1·63-2·03) in 2023, alongside a concurrent 4·1% (1·9-6·3) reduction in age-standardised rates. Based on DALY counts, the leading level 3 NCDs in 2023 were ischaemic heart disease (193 million [176-209] DALYs), stroke (157 million [141-172]), and diabetes (90·2 million [75·2-107]), with the largest increases in age-standardised rates since 2010 occurring for anxiety disorders (62·8% [34·0-107·5]), depressive disorders (26·3% [11·6-42·9]), and diabetes (14·9% [7·5-25·6]). Remarkable health gains were made for communicable, maternal, neonatal, and nutritional (CMNN) diseases, with DALYs falling from 874 million (837-917) in 2010 to 681 million (642-736) in 2023, and a 25·8% (22·6-28·7) reduction in age-standardised DALY rates. During the COVID-19 pandemic, DALYs due to CMNN diseases rose but returned to pre-pandemic levels by 2023. From 2010 to 2023, decreases in age-standardised rates for CMNN diseases were led by rate decreases of 49·1% (32·7-61·0) for diarrhoeal diseases, 42·9% (38·0-48·0) for HIV/AIDS, and 42·2% (23·6-56·6) for tuberculosis. Neonatal disorders and lower respiratory infections remained the leading level 3 CMNN causes globally in 2023, although both showed notable rate decreases from 2010, declining by 16·5% (10·6-22·0) and 24·8% (7·4-36·7), respectively. Injury-related age-standardised DALY rates decreased by 15·6% (10·7-19·8) over the same period. Differences in burden due to NCDs, CMNN diseases, and injuries persisted across age, sex, time, and location. Based on our risk analysis, nearly 50% (1·27 billion [1·18-1·38]) of the roughly 2·80 billion total global DALYs in 2023 were attributable to the 88 risk factors analysed in GBD. Globally, the five level 3 risk factors contributing the highest proportion of risk-attributable DALYs were high systolic blood pressure (SBP), particulate matter pollution, high fasting plasma glucose (FPG), smoking, and low birthweight and short gestation-with high SBP accounting for 8·4% (6·9-10·0) of total DALYs. Of the three overarching level 1 GBD risk factor categories-behavioural, metabolic, and environmental and occupational-risk-attributable DALYs rose between 2010 and 2023 only for metabolic risks, increasing by 30·7% (24·8-37·3); however, age-standardised DALY rates attributable to metabolic risks decreased by 6·7% (2·0-11·0) over the same period. For all but three of the 25 leading level 3 risk factors, age-standardised rates dropped between 2010 and 2023-eg, declining by 54·4% (38·7-65·3) for unsafe sanitation, 50·5% (33·3-63·1) for unsafe water source, and 45·2% (25·6-72·0) for no access to handwashing facility, and by 44·9% (37·3-53·5) for child growth failure. The three leading level 3 risk factors for which age-standardised attributable DALY rates rose were high BMI (10·5% [0·1 to 20·9]), drug use (8·4% [2·6 to 15·3]), and high FPG (6·2% [-2·7 to 15·6]; non-significant). INTERPRETATION: Our findings underscore the complex and dynamic nature of global health challenges. Since 2010, there have been large decreases in burden due to CMNN diseases and many environmental and behavioural risk factors, juxtaposed with sizeable increases in DALYs attributable to metabolic risk factors and NCDs in growing and ageing populations. This long-observed consequence of the global epidemiological transition was only temporarily interrupted by the COVID-19 pandemic. The substantially decreasing CMNN disease burden, despite the 2008 global financial crisis and pandemic-related disruptions, is one of the greatest collective public health successes known. However, these achievements are at risk of being reversed due to major cuts to development assistance for health globally, the effects of which will hit low-income countries with high burden the hardest. Without sustained investment in evidence-based interventions and policies, progress could stall or reverse, leading to widespread human costs and geopolitical instability. Moreover, the rising NCD burden necessitates intensified efforts to mitigate exposure to leading risk factors-eg, air pollution, smoking, and metabolic risks, such as high SBP, BMI, and FPG-including policies that promote food security, healthier diets, physical activity, and equitable and expanded access to potential treatments, such as GLP-1 receptor agonists. Decisive, coordinated action is needed to address long-standing yet growing health challenges, including depressive and anxiety disorders. Yet this can be only part of the solution. Our response to the NCD syndemic-the complex interaction of multiple health risks, social determinants, and systemic challenges-will define the future landscape of global health. To ensure human wellbeing, economic stability, and social equity, global action to sustain and advance health gains must prioritise reducing disparities by addressing socioeconomic and demographic determinants, ensuring equitable health-care access, tackling malnutrition, strengthening health systems, and improving vaccination coverage. We live in times of great opportunity. FUNDING: Gates Foundation and Bloomberg Philanthropies.

Wild Syrian rue (Peganum harmala L. family Zygophyllaceae) is well-known in Iran and various parts of this plant including, its seeds, bark, and root have been used as folk medicine. Recent years of research has demonstrated different pharmacological and therapeutic effects of P. harmala and its active alkaloids, especially harmine and harmaline. Analytical studies on the chemical composition of the plant show that the most important constituents of this plant are beta-carboline alkaloids such as harmalol, harmaline, and harmine. Harmine is the most studied among these naturally occurring alkaloids. In addition to P. harmala (Syrian rue), these beta-carbolines are present in many other plants such as Banisteria caapi and are used for the treatment of different diseases. This article reviews the traditional uses and pharmacological effects of total extract and individual active alkaloids of P. harmala (Syrian rue).

Schistosomes are digenean flukes, parasitic of birds, mammals and crocodiles. The family Schistosomatidae contains species of considerable medical and veterinary importance, which cause the disease schistosomiasis. Previous studies, both morphological and molecular, which have provided a good deal of information on the phylogenetics of this group, have been limited in the number of species investigated or the type or extent of molecular data used. This paper presents the most comprehensive phylogeny to date, based on the sequences of 3 genes, complete ribosomal small subunit rRNA and large ribosomal subunit rRNA, and mitochondrial cytochrome oxidase 1, sequenced from 30 taxa including at least 1 representative from 10 of the 13 known genera of the Schistosomatidae and 17 of the 20 recognized Schistosoma species. The phylogeny is examined using morphological characters, intermediate and definitive host associations and biogeography. Theories as to the origins and spread of Schistosoma are also explored. The principal findings are that Ornithobilharzia and Austrobilharzia form a sister group to the Schistosoma; mammalian schistosomes appear paraphyletic and 2 Trichobilharzia species, T. ocellata and T. szidati, seem to be synonymous. The position of Orientobilharzia within the Schistosoma is confirmed, as is an Asian origin for the Schistosoma, followed by subsequent dispersal through India and Africa.

There are many critical challenges in the use of primary and secondary cultures and their biological compounds in food commodities. An alternative is the application of postbiotics from the starter and protective lactic acid bacteria (LAB). The concept of postbiotics is relatively new and there is still not a recognized definition for this term. The word "postbiotics" is currently used to refer to bioactive compounds, which did not fit to the traditional definitions of probiotics, prebiotics, and paraprobiotics. Therefore, the postbiotics may be presently defined as bioactive soluble factors (products or metabolic byproducts), produced by some food-grade microorganisms during the growth and fermentation in complex microbiological culture (in this case named cell-free supernatant), food, or gut, which exert some benefits to the food or the consumer. Many LAB are considered probiotic and their postbiotic compounds present similar or additional health benefits to the consumer; however, this review aimed to address the most recent applications of the postbiotics with food safety purposes. The potential applications of postbiotics in food biopreservation, food packaging, and biofilm control were reviewed. The current uses of postbiotics in the reduction and biodegradation of some food safety-related chemical contaminants (e.g., biogenic amines) were considered. We also discussed the safety aspects, the obstacles, and future perspectives of using postbiotics in the food industry. This work will open up new insights for food applications of postbiotics prepared from LAB.

We investigate connectivity in the ad hoc network formed between vehicles that move on a typical highway. We use a common model in vehicular traffic theory in which a fixed point on the highway sees cars passing it that are separated by times with an exponentially distributed duration. We obtain the distribution of the distances between the cars, which allows us to use techniques from queuing theory to study connectivity. We obtain the Laplace transform of the probability distribution of the connectivity distance, explicit expressions for the expected connectivity distance, and the probability distribution and expectation of the number of cars in a platoon. Then, we conduct extensive simulation studies to evaluate the obtained results. The analytical model that we present is able to describe the effects of various system parameters, including road traffic parameters (i.e., speed distribution and traffic flow) and the transmission range of vehicles, on the connectivity. To more precisely study the effect of speed on connectivity, we provide bounds obtained using stochastic ordering techniques. Our approach is based on the work of Miorandi and Altman, which transformed the problem of connectivity distance distribution into that of the distribution of the busy period of an equivalent infinite server queue. We use our analytical results, along with common road traffic statistical data, to understand connectivity in vehicular ad hoc networks.

Mitogen-activated protein kinase (MAPK) signaling pathways organize a great constitution network that regulates several physiological processes, like cell growth, differentiation, and apoptotic cell death. Due to the crucial importance of this signaling pathway, dysregulation of the MAPK signaling cascades is involved in the pathogenesis of various human cancer types. Oxidative stress and DNA damage are two important factors which in common lead to carcinogenesis through dysregulation of this signaling pathway. Reactive oxygen species (ROS) are a common subproduct of oxidative energy metabolism and are considered to be a significant physiological modulator of several intracellular signaling pathways including the MAPK pathway. Studies demonstrated that the MAP kinases extracellular signal-regulated kinase (ERK) 1/2 and p38 were activated in response to oxidative stress. In addition, DNA damage is a partly common circumstance in cell life and may result in mutation, cancer, and even cell death. Recently, accumulating evidence illustrated that the MEK/ERK pathway is associated with the suitable performance of cellular DNA damage response (DDR), the main pathway of tumor suppression. During DDR, the MEK/ERK pathway is regularly activated, which contributes to the appropriate activation of DDR checkpoints to inhibit cell division. Therefore, the aim of this review is to comprehensively discuss the critical function of MAPK signaling in oxidative stress, DNA damage, and cancer progression.

Cancer is one of the major deadly diseases globally. The alarming rise in the mortality rate due to this disease attracks attention towards discovering potent anticancer agents to overcome its mortality rate. The discovery of novel and effective anticancer agents from natural sources has been the main point of interest in pharmaceutical research because of attractive natural therapeutic agents with an immense chemical diversity in species of animals, plants, and microorganisms. More than 60% of contemporary anticancer drugs, in one form or another, have originated from natural sources. Plants and microbial species are chosen based on their composition, ecology, phytochemical, and ethnopharmacological properties. Plants and their derivatives have played a significant role in producing effective anticancer agents. Some plant derivatives include vincristine, vinblastine, irinotecan, topotecan, etoposide, podophyllotoxin, and paclitaxel. Based on their particular activity, a number of other plant-derived bioactive compounds are in the clinical development phase against cancer, such as gimatecan, elomotecan, etc. Additionally, the conjugation of natural compounds with anti-cancerous drugs, or some polymeric carriers particularly targeted to epitopes on the site of interest to tumors, can generate effective targeted treatment therapies. Cognizance from such pharmaceutical research studies would yield alternative drug development strategies through natural sources which could be economical, more reliable, and safe to use.

In the present study, Fe3O4@SiO2 core–shell microspheres were prepared via two steps. First, Fe3O4 nanoparticles were synthesized by co-precipitation of Fe+3 and Fe+2 as reaction substrates and NaOH as precipitant. Second, the surface of Fe3O4 was coated with silica by hydrolysis of tetraethylorthosilicate as the silica source. Subsequently, in order to reduce the amount of interaction and the agglomeration of Fe3O4@SiO2 microspheres, the silica shell of these particles was modified by vinyltriethoxysilane as the silane coupling agent. The structural properties of the samples were characterized by X-ray diffraction, scanning electron microscopy, transmission electron microscopy, and Fourier transform infrared spectroscopy analyses. The results indicated that the average sizes of Fe3O4 and Fe3O4@SiO2 particles were about 50 and 500 nm, respectively. Also, the surface characterization of Fe3O4@SiO2 microspheres showed that the silane coupling agent was covalently coupled with the silica surface.

Heat stress negatively influences human health and performance, and leading to lower efficiency in daily activities. The present study sought to examine the relationship between UTCI, other heat indices (SET, PET, PMV, PPD, and WBGT), and environmental parameters. Daily data, encompassing a 12 month period in 2016 (from 6 a.m. to 9 p.m. for each day), were retrieved from the Meteorological Organization of Kerman. The data were fed into SPSS 20, followed by conducting Pearson product moment correlation and linear regression to find the association between UTCI and other heat indices/environmental parameters. Excel 2016 was also utilized to draw the relevant diagrams. Significant correlations were detected between UTCI and other heat indices (SET, PET, PMV, and WBGT). UTCI also was measurably correlated with environmental parameters like dry temperature (P < 0.0001). The highest correlation coefficient was observed between UTCI and PET (r = 0.96). UTCI also had strong correlations with WBGT (r = 0.88), SET (r = 0.87), and dry temperature (r = 0.90). Thus, indices that are calculated based on body thermal equation (i.e. SET and PET) are more strongly connected with UTCI, registering a better slope. On the other hand, WBGT is more similar to UTCI (than other indices) in terms of thermal perception. Keywords: Heat indices, Heat, Thermal climate, Temperature

Hydrological droughts are characterized based on their duration, severity, and magnitude. Among the most critical factors, precipitation, evapotranspiration, and runoff are essential in modeling the droughts. In this study, three indices of drought, i.e., Standardized Precipitation Index (SPI), Standardized Streamflow Index (SSI), and Standardized Precipitation Evapotranspiration Index (SPEI), are modeled using Support Vector Regression (SVR), Gene Expression Programming (GEP), and M5 model trees (MT). The results indicate that SPI delivered higher accuracy. Moreover, MT model performed better in predicting SSI by a CC of 0.8195 and a RMSE of 0.8186.Abbreviations: ANFIS: adaptive neuro-fuzzy inference system; ANN: artificial neural network; ANN: artificial neural network; BS-SVR: boosted-support Vector Regression; CC: correlation coefficient; ELM: extreme learning machine; GEP: gene Expression Programming; GP: genetic Programming; GPR: Gaussian process regression; KNN: k-nearest neighbor; LSSVM: least squares Support Vector Machine; LSSVR: least support vector regression; MAE: mean absolute error; MARS: multivariate adaptive regression splines; MLP: multilayer perceptron; MLR: multiple linear regression; MT: M5 model tree; P: precipitation; PDSI: palmer drought severity index; PET: potential evapotranspiration; RAE: relative absolute error; RMSE: root mean square error; RVM: relevance vector machine; SAR: sodium absorption index; SDR: standard deviation reduction; SPEI: standardized precipitation evapotranspiration index; SPI: standardized precipitation index; SSI: standardized streamflow index; SVM: support vector machine; SVR: support vector regression; WAANN: Wavelet-ARIMA-ANN; WANFIS: Wavelet-Adaptive Neuro-Fuzzy Inference System; WN: wavelet network