Spatial association of homicide rate with violence, sociodemographic, and public security factors: global burden of disease study 2018 for municipalities in Brazil.

OBJECTIVES: To analyse spatial-temporal changes and spatial association of homicide rates with violence, sociodemographic, public security and human rights indicators in Brazilian municipalities. STUDY DESIGN: An ecological study using homicide estimates from the Global Burden of Disease and population from the Brazilian Ministry of Health, 2000 to 2018. The explanatory variables come from the systems of mortality, notifications of violence and security, and the Brazilian Institute of Geography and Statistics. METHODS: Moran indices and maps identified clusters of high and low risk for homicides in three trienniums (p < 0.05). Multivariate linear and spatial regressions estimated explanatory factors' contributions for the last triennium. RESULTS: Municipalities with high rates of homicides (>34/100,000) doubled, reaching 21.5 %. Those rates were concentrated in big cities, and increased in smaller municipalities. Increases in critical areas were found in the Northeast and North regions: more than 40 % in the states of Sergipe, Bahia, Ceará, Rio Grande do Norte and Roraima. Decreases occurred in the Southeast and Midwest regions: more than 35 % in São Paulo and Rio de Janeiro states. The spatial model, with an 18.9 % higher R2 (0.706), showed a positive association for records of violence, Blacks, low-level education, municipalities >50,000 inhabitants and municipalities with homicide and municipal police. CONCLUSIONS: An increase in and the interiorisation of homicide risk areas in Brazil was observed, with displacement among regions (from the Southeast to the North/Northeast). The level of violence was the main explanatory factor for homicides. Territorial space proved to be important to understand and prevent lethal crime.

Leprosy in Brazil: an analysis of the Global Burden of Disease estimates between 1990 and 2019.

OBJECTIVE: To analyze the occurrence of leprosy in Brazil and its states between 1990 and 2019, according to Global Burden of Disease (GBD) estimates, and its correlation with development status. STUDY DESIGN: A descriptive and analytical ecological epidemiological study. METHODS: Rates of incidence, prevalence, and years lived with disability (YLD) due to leprosy, standardized by age, per 100,000 inhabitants, were analyzed. The trend analysis consisted of the joinpoint regression model and the average annual percentage change. The correlation between the incidence rate and the sociodemographic index (SDI) was investigated (Spearman test) at a 5% significance level. Incidence, prevalence and YLD rates were presented by country's states, sex, and age. RESULTS: There was an average percentage decrease of -1.1% per year (P < 0.001) in the incidence rate in the country and, between 1990 and 2019, a decline from 4.8 to 3.5 per 100,000 inhabitants; prevalence from 26.1 to 22.2, and YLD from 1.1 to 1.0. The incidence rate was higher among men and the elderly. Maranhão (7.0 in 1990; 4.2 in 2019), Alagoas (6.6 in 1990; 4.1 in 2019), Acre (6.1 in 1990; 4.0 in 2019), Mato Grosso (5.2 in 1990 and 3.7 in 2019), and Mato Grosso do Sul (4.8 in 1990 and 3.7 in 2019) presented the highest incidence rates. A negative correlation was observed between SDI levels and leprosy incidence rates in 1990 (R = -0.71; P < 0.0001) and 2019 (R = -0.81; P < 0.0001). CONCLUSIONS: Despite the decrease in the rates of leprosy incidence, prevalence, and YLDs over the analyzed period, Brazil has a long way towards achieving its eradication. The greater burden of the disease in males stands out. The estimated risk of the disease was higher in the states with the lowest SDI levels. Therefore, interventions must consider the heterogeneity of the disease burden geographically and between sociodemographic groups.

Mortality due to cervical and breast cancer in health regions of Brazil: impact of public policies on cancer care.

OBJECTIVE: This analysis assessed the association between regional income, screening coverage for cervical and breast cancer, and temporal trends in mortality from these cancers in different Brazilian health regions. STUDY DESIGN: Spatiotemporal ecological study across 450 health regions of Brazil. METHODS: Data from 2010 Demographic Census were used to assess income. Variations in income distribution within health regions were measured using the Gini index. Data on screening coverage were obtained from the Ambulatory Information System (SIA/SUS). Mortality was assessed from the Global Burden of Disease Study 2019 data. The average annual percentage change (AAPC) in cervical and breast cancer mortality rates, 2010-2018, was calculated by health regions. Results were presented in regional maps. The associations between income, screening coverage and mortality changes were estimated by bivariate spatial correlation. RESULTS: Health regions located in the South and Southeast regions of Brazil had the greatest percentages of screening coverage and highest per capita incomes with the lowest Gini index values. From 2010 to 2018, mortality rates for cervical cancer were highest in the North and Northeast health regions. Breast cancer mortality rates were highest in the South and Southeast health regions. The AAPC in breast and cervical cancer mortality had a negative association with per capita income and screening coverage, and a positive association with the Gini index. CONCLUSIONS: There are large regional variations in income, screening coverage, and mortality rates for women with breast and cervical cancer. These inequities could be mitigated by policies to address income disparities and improved access to screening.

Mortality by avoidable causes in Brazil from 1990 to 2019: data from the Global Burden of Disease Study.

OBJECTIVES: The aim of this study was to analyse the trends of avoidable mortality in Brazil from 1990 to 2019 and its correlation with sociodemographic indexes (SDIs). STUDY DESIGN: Epidemiological mortality trends. METHODS: This study analysed data from the Global Burden of Disease database. The list of causes of avoidable death, as proposed by Nolte and McKee, was applied and included 32 causes. The current study used age-standardised mortality rates and the rates of change, in addition to a correlation analysis between avoidable death and the SDI. RESULTS: Mortality rates decreased from 343.90/100,000 inhabitants in 1990 to 155.80/100,000 inhabitants in 2019. Infectious diseases showed the largest decline in mortality rates, but notable decreases were also found for diarrhoeal diseases (-94.9%), maternal conditions (-66.5%) and neonatal conditions (-60.5%). Mortality rates for non-communicable diseases (NCDs) also decreased (-48%) but maintained a similar absolute number of deaths in 2019 compared with 1990. Decreased mortality rates were also found for ischaemic heart disease (-49.1%), stroke (-61.4%) and deaths due to adverse effects caused by medical treatments (-26.2%). Avoidable mortality rates declined in all of the 27 Brazilian states, and a high correlation was found between deaths and SDI (R = -0.74; P < 0.000001). CONCLUSIONS: A reduction in avoidable deaths was found throughout Brazil over the study period, although major regional inequalities were revealed. Richer states presented the best overall reduction in mortality rates. The biggest decreases in mortality were seen in maternal and paediatric infectious diseases in the poorest states due to the expansion of the Primary Health System and improvements in sanitation. Today, NCDs predominate and efforts should be made to formulate public policies for the prevention and control of NCDs.

Sustainable Development Goals' health-related indicators for Brazil and Ecuador: an analysis for the period of 1990-2019.

OBJECTIVE: This article aims to analyse the evolution of 40 Sustainable Development Goals' (SDGs) health-related indicators in Brazil and Ecuador from 1990 to 2019. STUDY DESIGN: Epidemiological study of long-term trends in 40 SDGs' health-related indicators for Brazil and Ecuador from 1990 to 2019, using estimates from the Global Burden of Disease Study. METHODS: Forty SDGs' health-related indicators and an index from 1990 to 2017 for Brazil and Ecuador, and their projections up to 2030 were extracted from the Institute for Health Metrics and Evaluation's Global Burden of Disease website and analysed. The percent annual change (PC) between 1990 and 2019 was calculated for both countries. RESULTS: Both countries have made progress on child stunting (Brazil: PC = -38%; Ecuador: PC = -43%) and child wasting prevalences (Brazil: PC = -42%; Ecuador: PC = -41%), percent of vaccine coverage (Brazil: PC = +215%; Ecuador: PC = +175%), under-5 (Brazil: PC = -75%; Ecuador: PC = -60%) and neonatal mortality rates (Brazil: PC = -69%; Ecuador: PC = -51%), health worker density per 1000 population (Brazil: PC = +153%; Ecuador: PC = +175%), reduction of neglected diseases prevalences (Brazil: PC = -40%; Ecuador: PC = -58%), tuberculosis (Brazil: PC = -27%; Ecuador: PC = -55%) and malaria incidences (Brazil: PC = -97%; Ecuador: PC = -100%), water, sanitation and hygiene mortality rates (Brazil and Ecuador: PC = -89%). However, both countries did not show sufficient improvement in maternal mortality ratio to meet SDGs targets (Brazil: PC = -37%; Ecuador: PC = -40%). Worsening of indicators were found for violence, such as non-intimate partner violence for both countries (Brazil: PC = +26%; Ecuador: PC = +18%) and suicide mortality rate for Ecuador (PC = +66%), child overweight indicator for Brazil (PC = -67%), disaster mortality rates (Brazil: PC = +100%; Ecuador: PC = +325%) and alcohol consumption (Brazil: PC = +46%; Ecuador: PC = +35%). CONCLUSIONS: Significant improvements are necessary in both countries requiring the strengthening of health and other policies, particularly concerning the prevention and management of violence and alcohol consumption, and preparedness for dealing with environmental disasters.

Chagas disease deaths detected among garbage codes registered in mortality statistics in Brazil: a study from the buRden of ChAgas dISEase in the contemporary world (RAISE) project.

OBJECTIVES: The objective of this study was to identify Brazil's most critical garbage codes (GCs) reclassified to Chagas disease (ChD) in mortality data and their proportions. We also estimated the potential impact of misclassification on the number of deaths attributed to ChD. STUDY DESIGN: Population-based descriptive study. METHODS: We used the Mortality Information System (SIM; in Portuguese) data before and after routine GC investigation in 2015-2019 to evaluate ChD deaths detected among them. We identified priority GCs, which contributed more than 0.1 % to the percentage of total ChD deaths registered. Spearman's correlation was used to evaluate the association between the reclassification of priority GCs and ChD prevalence. Then, we applied the GC correction factors to estimate the number of deaths attributed to ChD. RESULTS: 22,154 deaths were reported as ChD in the study period. Among them, 1004 deaths originally listed as priority GCs were deaths reclassified to ChD after an investigation in the SIM final database. Unspecific cardiomyopathy (10.2 %), unspecific heart diseases (4.7 %), and heart failure (2.8 %) were GCs with the highest proportions of reclassification to ChD in Brazil. Higher ChD prevalence at the state level was associated with a higher proportion of GC deaths reclassified as ChD. When applying correction factors identified after investigation, we estimated an increase of 26.4 % in registered ChD deaths, mostly in states with higher endemicity. CONCLUSIONS: GCs might conceal deaths due to ChD, particularly in Brazil's states with higher endemicity. The approach suggested in this study may offer an alternative method for estimating ChD-related deaths in endemic countries.

Undernutrition, and overweight and obesity: the two faces of malnutrition in Brazil, analysis of the Global Burden of Disease, 1990 to 2019.

OBJECTIVES: The objective of this study was to analyse the global burden of disease attributable to undernutrition and high body mass index (BMI) in Brazil and its 27 states, as well as its association with the socio-demographic index (SDI) from 1990 to 2019. STUDY DESIGN: This is an epidemiological time-series study. METHODS: This study analysed the undernutrition and high BMI estimated by the Global Burden of Disease study conducted from 1990 to 2019 for Brazil and its states, using the following metrics: absolute number of deaths, standardised mortality rate, and disability-adjusted life years (DALYs). This study also analysed the correlation between the percentage variation of mortality rates and SDI. RESULTS: A decrease in the number of deaths (-75 %), mortality rate (-75.1 %), and DALYS (-72 %) attributable to undernutrition was found in Brazil and in all regions. As regarding the high BMI, an increase in the number of deaths was found (139.6 %); however, the mortality rate (-9.7) and DALYs (-6.4 %) declined in all regions, except in the North and Northeast regions, which showed an increase. A strong correlation was identified between undernutrition and high BMI with SDI. CONCLUSION: Our study observed a double burden of malnutrition in Brazil, with a reduction in the burden of diseases due to malnutrition in Brazil and variation in the burden due to high BMI according to the socioeconomic status of the region. Public policies are necessary in order to guarantee the human right to a healthy and sustainable diet, together with food and nutrition security and a diminishing of social inequality.

Burden of non-communicable diseases and the achievement of the sustainable development goals in 2030 in Mercosur countries.

OBJECTIVES: The aims of this article were to analyse the burden of NCDs and their RFs in the Mercosur countries between 1990 and 2019 and to project mortality trends for 2030. STUDY DESIGN: Epidemiological study of time series. METHODS: The present study used data from the Global Burden of Disease study. The absolute number of deaths, mortality rates, disability-adjusted life years, years of life lost, years lived with disability and the burden of premature mortality by NCD attributable to the RFs were evaluated. Projections were made up to 2030. Age-standardised rates were used to draw comparisons by years and by countries. The analysis was conducted using the RStudio software. RESULTS: Between 1990 and 2019, a decrease was found in the premature mortality rates caused by NCDs in all the countries, except for Paraguay, which remained stable. When analysing premature mortality rates due to NCDs up to 2030, it was predicted that none of the countries would achieve the sustainable development goal of a one-third reduction in premature mortality by NCDs. Regarding the impacts of the RFs for NCDs, smoking, dietary risks, high blood pressure (BP) and high body mass index (BMI) were the main risks attributable to premature deaths due to NCDs. CONCLUSIONS: The results showed that mortality rates are declining in Mercosur countries; however, none of the countries are predicted to achieve the sustainable development goal of a one-third reduction in mortality due to NCDs by 2030. In addition to access to adequate treatment, progress is required in public regulation actions to reduce RFs, such as smoking, dietary risks, high BP and high BMI.

Mortality by road transport injury in Brazilian municipalities between 2000 and 2018.

OBJECTIVES: This study aimed to investigate patterns of mortality by road transport injury (RTI) in Brazilian municipalities, focused on deaths of motorcyclists, between 2000 and 2018, and their relation with population size and economic status. STUDY DESIGN: This was an ecological epidemiological study with a descriptive and analytical nature. METHODS: The age-standardized RTI mortality rates were calculated for the Brazilian municipalities, referring to the 3-year periods of 2000/2002 (T1), 2009/2011 (T2), and 2016/2018 (T3). The rates were stratified according to macroregion and population size and were compared in terms of percentage variation from one 3-year period to another. The Moran Global and Local indices were used in the spatial point-pattern analysis of the rates. To verify the association with the gross domestic product (GDP) per capita, the Spearman correlation coefficient was applied. RESULTS: A decline in RTI mortality rates was found between 2000 and 2018, with the most significant declines observed in municipalities from the South and Southeast regions of Brazil. However, increases were observed among motorcyclists. Clusters of municipalities were detected, which presented high mortality rates among the motorcyclists in the Northeast region and in some states of the North and Midwest regions. The mortality rates showed a negative correlation with the GDP per capita of the Brazilian municipalities. CONCLUSIONS: Although there were decreases in RTI mortality rates between 1990 and 2018, there was a significant increase in deaths among motorcyclists, especially in the Northeast, North, and Midwest regions of the country. Such differences can be explained by unequal growth in the size of the motorcycle fleet in those regions, by less law enforcement capability, and by the implementation of educational actions.

Burden of neurodegenerative diseases in the Eastern Mediterranean Region, 1990-2016: findings from the Global Burden of Disease Study 2016.

BACKGROUND AND PURPOSE: The Eastern Mediterranean Region (EMR) is experiencing a demographic shift towards rapid aging at a time of political unrest. We aimed to estimate the burden of neurodegenerative disorders and its relationship with sociodemographic index in the EMR countries from 1990 to 2016. METHODS: Using data from the Global Burden of Disease Study 2016, we calculated country-specific trends for prevalence, mortality, disability-adjusted life-years (DALY), years of life lost and years lived with disability (YLD) for Alzheimer's disease/other dementias and Parkinson's disease in the EMR during 1990-2016. RESULTS: In the EMR, the age-standardized prevalence rate of Alzheimer's disease/other dementias and Parkinson's disease was estimated at 759.8/100 000 (95% uncertainty intervals, 642.9-899.9) and 87.1/100 000 (95% uncertainty intervals, 69.8-108.2) people in 2016, demonstrating 0.01% and 42.3% change from 1990, respectively. Neurodegenerative disorders contributed to 5.4% of total DALY and 4.6% of total YLD among the older EMR population (70 years of age or older in 2016). Age-standardized DALY due to Parkinson's disease were strongly correlated with the sociodemographic index level (r = 0.823, P < 0.001). The YLD:DALY ratio of neurodegenerative diseases declined during this period in the low-income but not the high-income EMR countries. CONCLUSIONS: Our findings demonstrated an increasing trend in the burden of dementias and Parkinson's disease in most EMR countries between 1990 and 2016. With aging of the EMR populations, countries should target the modifiable risk factors of neurodegenerative diseases to control their increasing burden.

The global burden of melanoma: results from the Global Burden of Disease Study 2015.

BACKGROUND: Despite recent improvements in prevention, diagnosis and treatment, vast differences in melanoma burden still exist between populations. Comparative data can highlight these differences and lead to focused efforts to reduce the burden of melanoma. OBJECTIVES: To assess global, regional and national melanoma incidence, mortality and disability-adjusted life year (DALY) estimates from the Global Burden of Disease Study 2015. METHODS: Vital registration system and cancer registry data were used for melanoma mortality modelling. Incidence and prevalence were estimated using separately modelled mortality-to-incidence ratios. Total prevalence was divided into four disease phases and multiplied by disability weights to generate years lived with disability (YLDs). Deaths in each age group were multiplied by the reference life expectancy to generate years of life lost (YLLs). YLDs and YLLs were added to estimate DALYs. RESULTS: The five world regions with the greatest melanoma incidence, DALY and mortality rates were Australasia, North America, Eastern Europe, Western Europe and Central Europe. With the exception of regions in sub-Saharan Africa, DALY and mortality rates were greater in men than in women. DALY rate by age was highest in those aged 75-79 years, 70-74 years and ≥ 80 years. CONCLUSIONS: The greatest burden from melanoma falls on Australasian, North American, European, elderly and male populations, which is consistent with previous investigations. These substantial disparities in melanoma burden worldwide highlight the need for aggressive prevention efforts. The Global Burden of Disease Study results can help shape melanoma research and public policy.

Bulked segregant analysis for relative water content to detect quantitative trait loci in wheat under drought stress.

This study was carried out to evaluate the genetic effect of quantitative trait loci (QTLs) conferring drought tolerance in wheat. A population of 120 F(2) individuals from the cross between the drought-tolerant S-78-11 and drought-sensitive Tajan cultivars were analyzed for their segregation under drought stress conditions. The relative water content under drought stress conditions exhibited continuous variation, indicating the minor gene effects on the trait. Single-marker analysis (SMA) was carried out to detect the main QTL association with drought tolerance. The SMA results revealed that the simple sequence repeat markers GWM182 and GWM292 on chromosome 5D and GWM410 on chromosome 5A exhibited significant association with drought tolerance, accounting for 30, 22, and 21% of the total variation, respectively. The 3 genetic loci, especially GWM182, can be used in marker-assisted selection methods in drought tolerance breeding in wheat.

Abscisic acid crosstalk with auxin and ethylene in biosynthesis and degradation of inulin-type fructans in chicory.

The effect of different hormones on fructan accumulation and the genes regulating biosynthesis and degradation is known; however, information on hormonal interaction mechanisms for fructan content and mean degree of polymerization (mDP) is limited. Cell suspension cultures of chicory were prepared and treated with abscisic acid (ABA), auxin (AUX), ethylene (ETH), ABA + AUX or ABA + ETH, then inulin concentration, mDP of inulin and expression of FAZY genes was determined. A low concentration of AUX and ETH increased fructan content, while a high concentration of AUX and ETH decreased it. Exogenous ABA increased mDP of inulin and this coincided with the low expression of 1-FEHII. In hormone interactions, ABA changed and adjusted the effect of both AUX and ETH. ABA, together with a low level of AUX and ETH, resulted in a decrease in inulin content and increase in mDP, which coincided with low expression of FEHII. ABA together with a high level of AUX and ETH caused an increase in inulin content with a lower mDP, which coincided with high expression of biosynthesis (1-FFT) and degradation (1-FEHII) genes. The effect of both AUX and ETH was almost the same, although the effect of ETH was more severe. ABA had a modulating role in combinations with AUX and ETH. Among biosynthesis and degradation genes, the expression of 1-FEHII was more affected by these hormones.

Building national estimates of the burden of road traffic injuries in developing countries from all available data sources: Iran.

OBJECTIVE: To use a range of existing information sources to develop a national snapshot of the burden of road traffic injuries in one developing country-Iran. METHODS: The distribution of deaths was estimated by using data from the national death registration system, hospital admissions and outpatient visits from a time-limited hospital registry in 12 of 30 provinces, and injuries that received no institutional care using the 2000 demographic and health survey. Results were extrapolated to national annual incidence of health burden differentiated by age, sex, external cause, nature of injuries and institutional care. RESULTS: In 2005, 30,721 Iranians died annually in road traffic crashes and over one million were injured. The death rate (44 per 100,000) is the highest of any country in the world for which reliable estimates are available. Road traffic injuries are the third leading cause of death in Iran. While young adults are at high risk in non-fatal crashes, the elderly have the highest total death rates, largely due to pedestrian crashes. While car occupants lead the death count, motorized two-wheeler riders dominate hospital admissions, outpatient visits and health burden. CONCLUSIONS: Reliable estimates of the burden of road traffic injuries are an essential input for rational priority setting. Most low income countries are unlikely to have national injury surveillance systems for several decades. Thus national estimates of the burden of injuries should be built by collating information from all existing information sources by appropriately correcting for source specific shortcomings.

Injury incidence, healthcare consumption and avenues for prevention: a household survey on injury in rural Twiserkan, Iran.

OBJECTIVES: To assess the incidence rates of injuries of various levels of severity, and to document people's healthcare-seeking behaviours in case of injury and their views regarding the potential contribution of various actors for injury control and prevention. STUDY DESIGN: Community-based household survey in the Twiserkan district, Iran. METHODS: A questionnaire-based interview survey was undertaken over a 3-week period in June 2006, and a cluster sample of households (n=759) was visited by 10 pre-trained field workers. Denominator data were obtained from the Twiserkan district health centre. Gender- and age-specific injury distribution data were compiled by mechanism of injury. RESULTS: The overall estimated annual incidence rate of injuries was 91/1000 person-years (10 for hospitalization and 81 for other medical attendance). Traffic and falls were the most common mechanisms of injury (n=22 and 19, respectively); traffic injuries were more common among men and falls injuries were more common among women. Both mechanisms of injury were more common among adults (aged > or =16 years). Most people with severe injuries and nearly half of those people with moderate injuries initially sought care at hospital, whereas all people with minor injuries initially presented at their local health house. Common suggestions for injury prevention included engineering changes (authorities), safety education (local health workers) and increased cooperation (citizens). CONCLUSIONS: In the rural area studied, the incidence of injuries is high. Injuries affecting children and males are more severe, and many of these are related to traffic and falls. The rural healthcare system appears to be accessible to people for trauma care. A range of context-relevant injury counter-measures were proposed by injured and non-injured laypeople.

Direct estimation of life expectancy in the Islamic Republic of Iran in 2003.

We estimated the life expectancy for 2003 for 23 provinces in the Islamic Republic of Iran using population and mortality data from the Ministry of Health and Medical Education. The underreporting of deaths above 4 years was corrected using the Brass Growth Balance method. We assumed that the distributions of population, deaths, and hence life expectancy in the 23 provinces were equal to those for all 28 provinces of the country. Thus we estimated life expectancy at birth to be 71.56 years for the total population [95% uncertainty interval (UI): 71.52-71.62]; 70.09 (95% UI: 70.02-70.16) years for males, and 73.17 (95% UI: 73.10-73.24) years for females. Our estimates were higher than the model-based estimates of the Statistical Centre of Iran, United Nations agencies and the World Bank, due to differences in the estimation methods used.

Caesarean section in the Islamic Republic of Iran: prevalence and some sociodemographic correlates.

The aim of this study was to investigate the prevalence of caesarean section in the Islamic Republic of Iran in different provinces and to compare the sociodemographic characteristics of married women with and without caesarean section. Data were analysed from the Iranian Demographic and Health Survey of a representative sample of married women (n = 17,991) who delivered a baby between September 1998 and October 2000. Overall, 35.0% of deliveries were by caesarean section. Women having a caesarean section were older, better educated, married at a later age and with lower parity than those who delivered normally. Provincial variations in rates were significantly correlated with indices of socioeconomic development.

Phyto-miRNA: A molecule with beneficial abilities for plant biotechnology.

The discovery of the phenomenon of gene silencing in 1990s opened new doors to biotechnology and plant breeding in order to supply food security. Food Security, as defined by FAO, it exists when all people, at all times, have economic access to safe, sufficient and nutritious food to meet their dietary needs and food preferences for a healthy and active life. Due to the need to ensure food security and also gene silencing potentials, research in this field began with astonishing speed and even it still continues. In this field, miRNA-associated gene silencing especially attracted the attention of scientists in order to decrypt the genes involved in process such as plant growth and development, metabolism, signal transduction, response against environmental stresses, nodule development in legumes and inducement male sterility. In addition, miRNA found a lot of applications in plant biotechnology like miRNA-based molecular markers and miRNA-based molecular breeding for plants improvement. Given to the growing importance of plant miRNAs (Phyto-miRNAs) in biotechnology and expansion of their applications in molecular breeding, it is necessary to review miRNA in an up-to-date schema. In this study, it was presented both the necessary foundations of miRNAs and their important uses in plant sciences, such as molecular markers and metabolic engineering. As a result, we hope to expand the use of artificial miRNAs in plants engineering.

Phyto-miRNAs-based regulation of metabolites biosynthesis in medicinal plants.

Medicinal plants, are known to produce a wide range of plant secondary metabolites (PSMs) applied as insecticides, drugs, dyes and toxins in agriculture, medicine, industry and bio-warfare plus bio-terrorism, respectively. However, production of PSMs is usually in small quantities, so we need to find novel ways to increase both quantity and quality of them. Fortunately, biotechnology suggests several options through which secondary metabolism in plants can be engineered in innovative ways to: 1) over-produce the useful metabolites, 2) down-produce the toxic metabolites, 3) produce the new metabolites. Among the ways, RNA interference (RNAi) technology which involves gene-specific regulation by small non-coding RNAs (sncRNAs) have been recently emerged as a promising tool for plant biotechnologist, not only to decipher the function of plant genes, but also for development of the plants with improved and novel traits through manipulation of both desirable and undesirable genes. Among sncRNAs, miRNAs have been recorded various regulatory roles in plants such as development, signal transduction, response to environmental stresses, metabolism. Certainly, the use of miRNAs in metabolic engineering requires identification of miRNAs involved in metabolites biosynthesis, understanding of the biosynthetic pathways, as well as the identification of key points of the pathways in which the miRNAs have their own effect. Thus, we firstly consider these three issues on metabolic engineering of medicinal plants. Our review shows, application of miRNAs can open a novel perspective to metabolic engineering of medicinal plants.