Application of Artificial Intelligence in Tissue Engineering.

Tissue engineering, a crucial approach in medical research and clinical applications, aims to regenerate damaged organs. By combining stem cells, biochemical factors, and biomaterials, it encounters challenges in designing complex 3D structures. Artificial intelligence (AI) enhances tissue engineering through computational modeling, biomaterial design, cell culture optimization, and personalized medicine. This review explores AI applications in organ tissue engineering (bone, heart, nerve, skin, cartilage), employing various machine learning (ML) algorithms for data analysis, prediction, and optimization. Each section discusses common ML algorithms and specific applications, emphasizing the potential and challenges in advancing regenerative therapies.

Machine learning provides specific detection of salt and drought stresses in cucumber based on miRNA characteristics.

BACKGROUND: Specific detection of the type and severity of plant abiotic stresses helps prevent yield loss by considering timely actions. This study introduces a novel method to detect the type and severity of stress in cucumber plants under salinity and drought conditions. Various features, i.e., morphological (image textural features), physiological/biochemical (relative water content, chlorophyll, catalase activity, anthocyanins, phenol content, and proline), as well as miRNA characteristics (the concentration of miRNA-156a, miRNA-166i, miRNA-399g, and miRNA-477b) were extracted from plant leaves, and machine learning methods were used to predict the type and severity of stress by having these features. Support vector machine (SVM) with parameters optimized by genetic algorithm (GA) and particle swarm optimization (PSO) was used for machine learning. RESULTS: The coefficient of determination of predicting the stress type and severity in plants under both stresses was 0.61, 0.82, and 0.99 using morphological, physiological/biochemical, and miRNA characteristics, respectively. This reveals machine learning methods optimized by metaheuristic optimization techniques can provide specific detection of salt and drought stresses in cucumber plants based on miRNA characteristics. Among the study miRNAs, miRNA-477b and miRNA-399g had the highest and lowest contribution to salt and drought stresses, respectively. CONCLUSIONS: Comapred to conventional plant traits, miRNAs are more reliable features for providing us with valuable information about plant abiotic diseases at early stages. Using an electrochemical miRNA biosensor similar to one used in this work to measure the miRNA concentration in plant leaves and using a machine learning algorithm such as SVM enable farmers to detect the salt and drought stress at early stages in cucumber plants with very high accuracy.

Zeolitic imidazolate frameworks: From bactericidal properties to tissue regeneration.

Zeolitic imidazolate frameworks (ZIFs), as a very well-known subset of metal-organic frameworks (MOFs), have attracted considerable attention in biomedicine due to their unique structural features such as tunable pore size, high surface area, high thermal stability, biodegradability, and biocompatibility. Moreover, it is possible to load a wide variety of therapeutic agents, drugs, and biomolecules into ZIF structures during the fabrication process owing to the ZIFs' porous structure and concise synthesis methods under mild conditions. This review focuses on the most recent advances in the bioinspiration of ZIFs and ZIF-integrated nanocomposites in boosting antibacterial efficiencies and regenerative medicine capabilities. The first part summarizes the various synthesis routes and physicochemical properties of ZIFs, including size, morphology, surface, and pore size. The recent advancements in the antibacterial aspects of using ZIFs and ZIF-integrated nanocomposites as carriers for antibacterial agents and drug cargo are elaborated. Moreover, the antibacterial mechanisms based on the factors affecting the antibacterial properties of ZIFs such as oxidative stress, internal and external triggers, the effect of metal ions, and their associated combined therapies, are discussed. The recent trends of ZIFs and their composites in tissue regeneration, especially bone regeneration and wound healing, are also reviewed with in-depth perspectives. Finally, the biological safety aspects of ZIFs, the latest reports about their toxicity, and the future prospects of these materials in regenerative medicine have been discussed.

Microchip encapsulation and microRNA-7 overexpression of trabecular meshwork mesenchymal stem/stromal cells improve motor function after spinal cord injury.

Manipulation of stem cells and microencapsulation through microfluidic chips has shown more promising results in treating complex conditions, such as spinal cord injury (SCI), than traditional treatments. This study aimed to investigate the potency of neural differentiation and its therapeutic role in SCI animal model of trabecular meshwork mesenchymal stem/stromal cells (TMMSCs) via miR-7 overexpression and microchip-encapsulated. TMMSCs are transduced with miR-7 via a lentiviral vector (TMMSCs-miR-7[+]) and encapsulated in alginate-reduced graphene oxide (alginate-rGO) hydrogel via a microfluidic chip. Neuronal differentiation of transduced cells in hydrogel (3D) and tissue cultures plate (2D) was assessed by expressing specific mRNAs and proteins. Further evaluation is being carried out through 3D and 2D TMMSCs-miR-7(+ and -) transplantation into the rat contusion SCI model. TMMSCs-miR-7(+) encapsulated in the microfluidic chip (miR-7-3D) increased nestin, ß-tubulin III, and MAP-2 expression compared with 2D culture. Moreover, miR-7-3D could improve locomotor behavior in contusion SCI rats, decrease cavity size, and increase myelination. Our results revealed that miR-7 and alginate-rGO hydrogel were involved in the neuronal differentiation of TMMSCs in a time-dependent manner. In addition, the microfluidic-encapsulated miR-7 overexpression TMMSCs represented a better survival and integration of the transplanted cells and the repair of SCI. Collectively, the combination of miR-7 overexpression and encapsulation of TMMSCs in hydrogels may represent a promising new treatment for SCI.

Effect of selegiline as a monomine oxidase B inhibitor on the expression of neurotrophin mRNA levels in a contusion rat model of spinal cord injury.

OBJECTIVE: Spinal cord injury (SCI) is followed by a cascade of events at the site of injury, including vascular ischemia, an increase in free radicals, inflammation, and neuronal death. In these individuals, protection of nerves and supporting cells, as well as prevention of neuronal damage, may improve recovery opportunities. Neurotrophins are a family of polypeptides that regulate nerve differentiation, growth, and survival. Selegiline is a selective monoamine oxidase B (MAO-B) inhibitor used to treat Parkinson's disease. Selegiline has been found to have neuroprotective properties and may be useful for the expression of neurotrophins. The aim of this study was to evaluate the expression levels of neurotrophin genes in spinal cord rats treated with selegiline. METHODS: Rats were divided into four groups: injury (control), laminectomy, sham (injured rat received 1 ml saline intraperitoneally) and treatment (injured rat received 5 mg/kg selegiline intraperitoneally for 7 days; once a day). The BBB scale (Basso, Beattie and Bresnahan) was performed once a week for 4 weeks to assess motor function after a spinal cord injury. On day 28 after SCI, the rat was sacrificed and the spinal cord lesion removed. A real-time PCR approach was used to assess neurotrophin gene expression. RESULTS: The results showed that administration of selegiline improves locomotor function and increases mRNA levels of BDNF, GDNF, NT-3, and NT-4. CONCLUSION: In summary, the results of this study suggest that selegiline may be an appropriate treatment for spinal cord injuries.

Challenges of middle-aged men in utilizing new health services from primary health care providers' perspective: a qualitative study.

BACKGROUND: Despite its special importance among different age groups, the middle-aged male group has often been neglected in the Iranian health system. The aim of this study was to examine, from the perspective of primary health care providers, the challenges of middle-aged men in utilizing health services. METHODS: This is a qualitative research that was conducted using semi-structured interviews in 2020 in Shoushtar Faculty of Medical Sciences, Iran. The research population included 60 managers and staff of the health sector. To collect the data, a group discussion method was used based on purposive sampling method. Data analysis was done manually using the conventional content analysis method with data reduction. Lincoln & Guba's four criteria of credibility, dependability, confirmability, and transferability were used to assess the trustworthiness of the results. RESULTS: The challenges of middle-aged men to receive modern health services were identified in 35 codes, 9 categories and three main themes. These themes included Context, Content, and Process. The Context theme comprised the following three categories: personal, economic and sociocultural, and geographic factors. The Content theme contained two categories of staff and facilities. Finally, the Process theme included four categories of service quality, program management, system of information registration and follow-up, and health education and publicizing. CONCLUSION: Promoting middle-aged men's benefits from modern health services calls for overcoming three categories of challenges related to: context, content, and process. Time and place restrictions on access to services should be alleviated by empowering health care workers, improving their working conditions, and strengthening the facilities of comprehensive health service centers. In addition, with proper management of the family physician program and service provision at different levels, the coverage of services for middle-aged men can also be extended.

The optimal electrical stimulation for neural differentiation of conjunctiva mesenchymal stem cells.

AIMS: The combination of biomaterial conductive scaffolds and electrical stimulation (ES) dramatically promotes stem cell differentiation into electro-responsive cells like neural cells. In this study, we aimed to fabricate PCL/PPY nanofiber scaffolds through the electrospinning method and investigate the effect of ES duration on neural differentiation of Conjunctiva Mesenchymal Stem Cells (CJMSCs). METHODS: The topography of the fabricated scaffold was characterized using SEM and TEM microscopy, and its mechanical and other properties were determined by tensile, TGA, FTIR, and Contact angle tests. CJMSCs were seeded on the scaffolds and then subjected to electrical current (115 V m-1 at 100 Hz) with durations of 1, 3, and 7 min for 3 days. Then the effect of nanofiber scaffold and electrical currents on cell viability and expression of neural marker genes (Nestin, ß-tubulin, MAP-2) was investigated by MTT assay and qPCR analysis. RESULTS: Our results revealed the good biocompatibility of the PCL-PPy nanofiber scaffold, and according to q-PCR results, the electrical stimulation of 1 min day-1 for 3 days can induce neural differentiation of CJMSCs as indicated by the fold change of gene expression of Nestin (~127), B-tubulin (~30), and MAP-2 (~52). CONCLUSION: This study emphasizes that the utilization of an electrically conductive nanofibrous scaffold in conjunction with electrical current has potential applications in the field of neural tissue engineering.

Increased Expression of Tight Junction Proteins and Blood-Brain Barrier Integrity in MCAO Rats Following Injection of miR-149-5p.

Cerebral ischemia is a common neurodegenerative disease in which damage to the blood-brain barrier (BBB) is the main consequence. In cerebral ischemia, the level of miR-149-5p and tight junction proteins are decreased, while the level of Calpine is increased, finally leading to increased BBB permeability. This study investigated the effect of miR-149-5p mimic on the expression of Calpain, Occludin, and ZO-1 and the consequences of cerebral ischemia. Cerebral ischemia model was performed via middle cerebral artery occlusion (MCAO) method on female Wistar rats. Four groups of Wistar rats were studied: Sham, cerebral ischemia without treatment, Scramble miR, and miR-149-5p mimic treatment. Then, neurological defects and BBB permeability (via Evans blue staining), cerebral edema (cerebrospinal fluid percentage), and ZO-1, Occludin, and Calapin expression (by quantitative real time- PCR) were investigated. qRT-PCR results showed miR-149-5p expression decreases after cerebral ischemia induction. In addition, Occludin and ZO-1 expression significantly increased in miR-149-5p group. In contrast, Calapin expression, BBB permeability, brain water content and neurological defects were significantly decreased. It seems that the increased level of miR-149-5p exerts its protective effect on cerebral ischemia due to increasing of tight junction proteins.

The Incidence and Geographical Distribution of Brucellosis in Iran Using Geographic Information System and Prediction of its Incidence in 2021.

BACKGROUND: Brucellosis is one of the most challenging health issues in many developing countries including Iran. The purpose of this study is to investigate the incidence and geographical distribution of brucellosis using Geographic Information System (GIS) and to predict its incidence in Iran in 2021. METHOD: This is a descriptive-analytical cross-sectional study, which contains spatial and climatic information along with the prevalence rate of brucellosis in Iran. Disease information was obtained from the National Center for Infectious Diseases Management during 2011-2015. Then, Arc GIS version 9.3 was used to plot the geographical maps for the incidence and frequency of the disease. Using the Raster calculator tool, the disease prediction map for the future was plotted. For proper spatial distribution of hot and cold spots, Getis-Ord-Gi statistic was employed. FINDINGS: The highest incidence of brucellosis during 2009-2015 was observed in the western provinces of Iran (North Khorasan, South Khorasan and Razavi Khorasan provinces). The incidence of brucellosis in Iran decreased from 2009 to 2011 but it exhibited an increasing trend from 2011 to 2014. The provinces of Kurdistan, Lorestan, Ilam, Zanjan and Kermanshah may be among the hot spots in terms of brucellosis incidence in 2021. CONCLUSION: We predicted significant variations in brucellosis risk distribution in Iran in the coming years. In the western and northwestern provinces, which are among the high risk areas for the incidence of this disease in the future, this disease can pose a serious health threat to the residents of these areas.

Epidemiology incidence and geographical distribution of Meningitis using GIS and its incidence prediction in Iran in 2021.

Background: Meningitis is classified as a medical emergency where the identification and early treatment of bacterial meningitis can eliminate serious consequences, such as hearing loss, memory problems, learning disabilities, brain damage, seizures, and death. The purpose of this study was to investigate the incidence and geographical distribution of meningitis using Geographic Information system (GIS) and to predict its incidence in Iran in 2021. Methods: This was a descriptive analytical study. Information on pertussis was obtained from the Center for Communicable Diseases Control during 2010-2015. In the next step, ArcGIS 9.3 was used to prepare geographic maps of the disease incidence and frequency. Then, the disease prediction map was drawn using the Raster Calculator tool. Results: The results showed that the highest incidence of meningitis during 2010-2015 was in Qazvin, Qom, and Kurdistan provinces. The incidence of meningitis in Iran increased from 9.77 in 2010 to 10.33 in 2015. Based on the modeling results for Iran, Qom, Qazvin, Kurdistan, Hamadan, and Mazandaran provinces with 78.89%, 74.68%, 70.07%, 43.97%, and 22.93% of their areas (Km2) are at high risk for meningitis in the coming years, respectively. Conclusion: According to the results of this study, it can be concluded that Qom, Qazvin, Kurdistan, Hamedan, and Mazandaran provinces are at risk of the disease. Monitoring vaccination in high-risk groups can partially prevent the incidence of the disease in these areas.

Surface modification of neurotrophin-3 loaded PCL/chitosan nanofiber/net by alginate hydrogel microlayer for enhanced biocompatibility in neural tissue engineering.

This study prepared a novel three-dimensional nanocomposite scaffold by the surface modification of PCL/chitosan nanofiber/net with alginate hydrogel microlayer, hoping to have the privilege of both nanofibers and hydrogels simultaneously. Bead free randomly oriented nanofiber/net (NFN) structure composed of chitosan and polycaprolactone (PCL) was fabricated by electrospinning method. The low surface roughness, good hydrophilicity, and high porosity were obtained from the NFN structure. Then, the PCL/chitosan nanofiber/net was coated with a microlayer of alginate containing neurotrophin-3 (NT-3) and conjunctiva mesenchymal stem cells (CJMSCs) as a new stem cell source. According to the cross-sectional FESEM, the scaffold shows a two-layer structure with interconnected pores in the range of 20 µm diameter. The finding revealed that the surface modification of nanofiber/net by alginate hydrogel microlayer caused lower inflammatory response and higher proliferation of CJMSCs than the unmodified scaffold. The initial burst release of NT-3 was 69% in 3 days which followed by a sustained release up to 21 days. The RT-PCR analysis showed that the expression of Nestin, MAP-2, and ß-tubulin III genes were increased 6, 5.4, and 8.8-fold, respectively. The results revealed that the surface-modified biomimetic scaffold possesses enhanced biocompatibility and could successfully differentiate CJMSCs to the neuron-like cells.

Effect of total alkaloid extract of local Sophora alopecuroides on minimum inhibitory concentration and intracellular accumulation of ciprofloxacin, and acrA expression in highly resistant Escherichia coli clones.

OBJECTIVES: Multidrug-resistant phenotypes in Gram-negative bacteria such as Escherichia coli mainly result from overexpression of the AcrAB-TolC efflux pump. Efflux pump inhibitors may be obtained from plant extracts, such as alkaloid extract of Sophora spp. The aims of this study were to evaluate the antibacterial and anti-pump potential of local Sophora alopecuroides total alkaloid extract and commercial matrine in combination with ciprofloxacin in highly resistant E. coli clones. METHODS: Alkaloid extract of S. alopecuroides seeds was prepared by acid-base solution and chloroform extraction. The percentage of matrine in this extract was measured by high-performance liquid chromatography (HPLC). Minimum inhibitory concentrations (MICs) of the extract and matrine in combination with ciprofloxacin were determined by the microbroth dilution method. The anti-pump activity of these combined materials was measured by ciprofloxacin accumulation assay and real-time PCR. RESULTS: The alkaloid extract contained 31.2% matrine. A synergistic interaction [fractional inhibitory concentration index (FICI)=0.13] was seen between the extract (1.56mg/mL) and ciprofloxacin (1µg/mL) in highly resistant E. coli clones. A significant decrease (P<0.05) in the expression level of acrA was seen in the presence of ciprofloxacin in clones pre-treated with plant extract or matrine for 36h. Accumulation of ciprofloxacin enhanced 2.8- and 2-fold following addition of matrine and plant extract, respectively, in these clones. CONCLUSIONS: Alkaloid extract of local S. alopecuroides and matrine have anti-pump activity; further investigations are necessary to elucidate their exact mechanisms of action.

A cholera outbreak in Alborz Province, Iran: a matched case-control study.

OBJECTIVES: A total of 229 confirmed cholera cases were reported in Alborz Province during an outbreak that lasted from June 2011 to August 2011. This study aimed to identify potential sources of transmission in order to determine suitable interventions in similar outbreaks. In other words, the lessons learned from this retrospective study can be utilized to manage future similar outbreaks. METHODS: An age-matched and sex-matched case-control study was conducted during the outbreak. For each case, two control subjects were selected from the neighborhood. A case of cholera was defined as a bacteriologically confirmed case with signs and symptoms of cholera. This study was conducted from June 14, 2011 through August 23, 2011. The data were analyzed by calculating odds ratios (ORs) using the logistic regression method. RESULTS: In this outbreak, 229 confirmed cholera cases were diagnosed. The following risk factors were found to be associated with cholera: consumption of unrefrigerated leftover food (OR, 3.05; 95% confidence interval [CI], 1.72 to 5.41), consumption of vegetables and fruits in the previous three days (OR, 2.75; 95% CI, 1.95 to 3.89), and a history of traveling in the previous five days (OR, 5.31; 95% CI, 2.21 to 9.72). CONCLUSIONS: Consumption of vegetables and fruits has remained an unresolved risk factor in cholera outbreaks in Iran in recent years. In order to reduce the risk of cholera, sanitary standards for fruits and vegetables should be observed at all points from production to consumption, the population should be educated regarding hygienic food storage during outbreaks, and sanitary standards should be maintained when traveling during cholera outbreaks.

Epidemiologic and Drug Resistance Pattern of Vibrio cholerae O1 Biotype El Tor, Serotype Ogawa, in the 2011 Cholera Outbreak, in Alborz Province, Iran.

BACKGROUND: Although the national guidelines recommend special antibiotics, based on the antibiogram of National Reference Laboratory, it seems that, because of uncontrolled usage of antibiotics in the society and due to the changes in the serotypes causing the disease, it is essential to monitor the status of drug resistance, permanently, and to revise the current prescriptions guidelines. OBJECTIVES: This study aimed to assess the epidemiological aspects and drug resistance pattern of Vibrio cholerae O1, biotype El Tor, serotype Ogawa, in cholera outbreak, in Alborz province in Iran, during 2011. MATERIALS AND METHODS: This is a cross-sectional study, which reviews a cholera epidemic that occurred in Iran. A total of 9844 specimens were taken from suspected cases, among diarrheal patients, via rectal swabs. The specimens were placed in Cary-Blair transport medium and sent to laboratory. Samples were enriched, in alkaline peptone water, and isolated on thiosulphate-citrate-bile salt-sucrose agar. From the 244 confirmed cases, 239 cases underwent antibiogram test, via disk diffusion method and based on national committee for clinical laboratory standards (NCCLS) instructions. The standard Escherichia coli ATCC 25922 was used for antibiogram quality control and, eventually, all results were interpreted and reported using NCCLS standard table. RESULTS: In total, until October 22, 2011, which was announced as the end of outbreak, 9844 samples were taken from diarrheal patients. Regarding the type of V. cholerae, 244 El Tor biotype positive cases were reported. The case fatality rate was 1.3%. The mean age of patients was 37.8 years and the highest incidence rate occurred in the age group 21 - 30 years. After conducting antibiotic susceptibility test in the 244 V. cholerae, biotype El Tor, serotype Ogawa, it was found that ciprofloxacin had the highest level of antibiotic susceptibility (99.6%) and the highest level of antibiotic resistance was observed in co-trimoxazole (95.4%). CONCLUSIONS: The results of our study show that the resistances to doxycycline and tetracycline, which are mentioned in multiple resources, as the most common antibiotic drugs for treating cholera, are increasing.

Neonatal bacteriemia isolates and their antibiotic resistance pattern in neonatal insensitive care unit (NICU) at Beasat Hospital, Sanandaj, Iran.

Bacteremia continues to result in significant morbidity and mortality, particularly among neonates. There is scarce data on neonatal bacteremia in among Iranian neonates. In this study, we determined neonatal bacteremia isolates and their antibiotic resistance pattern in neonatal insensitive care unit at Beasat hospital, Sanandaj, Iran. During one year, all neonates admitted to the NICU were evaluated. Staphylococcal isolates were subjected to determine the prevalence of MRS and mecA gene. A total of 355 blood cultures from suspected cases of sepsis were processed, of which 27 (7.6%) were positive for bacterial growth. Of the 27 isolates, 20 (74%) were Staphylococcus spp as the leading cause of bacteremia. The incidence of Gram negative bacteria was 04 (14.8%). The isolated bacteria were resistant to commonly used antibiotics. Maximum resistance among Staphylococcus spp was against Penicillin, and Ampicillin. In our study, the isolated bacteria were 7.5 % Vancomycin and Ciprofloxacin sensitive. Oxacillin disk diffusion and PCR screened 35% and 30% mec a positive Staphylococcus spp. The spectrum of neonatal bacteremia as seen in NICU at Beasat hospital confirmed the importance of pathogens such as Staphylococcus spp. Penicillin, Ampicillin and Cotrimoxazol resistance was high in theses isolates with high mecA gene carriage, probably due to antibiotic selection.