Exosomes biogenesis was increased in metformin-treated human ovary cancer cells; possibly to mediate resistance.

BACKGROUND: Exosomes derived from tumor cells contribute to the pathogenesis of cancers. Metformin, the most usually used drug for type 2 diabetes, has been frequently investigated for anticancer effects. Here, we examined whether metformin affects exosomes signaling in human ovary cancer cells in vitro. METHODS: Human ovary cancer cells, including A2780 and Skov3 cells, were treated with metformin for either 24-48 h. Cell viability and caspase-3 activity were determined by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) and colorimetric assays respectively. Oil-Red-O staining and in vitro, scratch assays were used to examine cellular toxicity and wound healing rate. After treatment with metformin, exosomes were isolated from cells and quantified by acetylcholinesterase (AChE) assay, Dynamic Light Scattering (DLS), and their markers. Genes related to exosomes signaling were analyzed by real-time PCR or western blotting. RESULTS: Our results showed that metformin decreased the viability of both cells dose/time-dependently (P < 0.05). Metformin increased the activity of caspase-3 (P < 0.05) as well as the number of Oil-Red-O positive cells in both cell lines. In vitro scratch assay showed that the cell migration rate of metformin-treated cells was decreased (P < 0.05), whereas AChE activity of exosomes from metformin-treated cells was increased (P < 0.05). Concurrent with an increase in CD63 protein levels, expression of Alix, CD63, CD81, Lamp-2, and Rab27b up-regulated in treated cells (P < 0.05). CONCLUSION: Results indicated that metformin had a cytotoxic effect on ovary cancer cells and enhanced exosome biogenesis and secretion.

Optimization and miniaturization of SE-ECL for potential-resolved, multi-color, multi-analyte detection.

Electrochemiluminescence (ECL) is a bioanalytical technique with numerous advantages, including the potential for high temporal and spatial resolution, a high signal-to-noise ratio, a broad dynamic range, and rapid measurement capabilities. To reduce the complexity of a multi-electrode approach, we use a single-electrode electrochemiluminescence (SE-ECL) configuration to achieve the simultaneous emission and detection of multiple colors for applications that require multiplexed detection of several analytes. This method exploits intrinsic differences in the electric potential applied along single electrodes built into electrochemical cells, enabling the achievement of distinct colors through selective excitation of ECL luminophores. We present results on the optimization of SE-ECL intensity for different channel lengths and widths, with sum intensities being 5 times larger for 6 cm vs. 2 cm channels and linearly increasing with the width of the channels. Furthermore, we demonstrated for the first time that applying Alternating Current (AC) voltage within the single electrode setup for driving the ECL reactions has a dramatic effect on the emitted light intensity, with square waveforms resulting in higher intensities vs sine waveforms. Additionally, multiplexed multicolor SE-ECL on a 6.5 mm × 3.6 mm CMOS semiconductor image sensor was demonstrated for the first time, with the ability to simultaneously distinguish four different colors, leading to the ability to measure multiple analytes.

On-chip bioluminescence biosensor for the detection of microbial surface contamination.

Detection of microbial pathogens is important for food safety reasons, and for monitoring sanitation in laboratory environments and health care settings. Traditional detection methods such as culture-based and nucleic acid-based methods are time-consuming, laborious, and require expensive laboratory equipment. Recently, ATP-based bioluminescence methods were developed to assess surface contamination, with commercial products available. In this study, we introduce a biosensor based on a CMOS image sensor for ATP-mediated chemiluminescence detection. The original lens and IR filter were removed from the CMOS sensor revealing a 12 MP periodic microlens/pixel array on an area of 6.5 mm × 3.6 mm. UltraSnap swabs are used to collect samples from solid surfaces including personal electronic devices, and office and laboratory equipment. Samples mixed with chemiluminescence reagents were placed directly on the surface of the image sensor. Close proximity of the sample to the photodiode array leads to high photon collection efficiency. The population of microorganisms can be assessed and quantified by analyzing the intensity of measured chemiluminescence. We report a linear range and limit of detection for measuring ATP in UltraSnap buffer of 10-1000 nM and 225 fmol, respectively. The performance of the CMOS-based device was compared to a commercial luminometer, and a high correlation with a Pearson's correlation coefficient of 0.98589 was obtained. The Bland-Altman plot showed no significant bias between the results of the two methods. Finally, microbial contamination of different surfaces was analyzed with both methods, and the CMOS biosensor exhibited the same trend as the commercial luminometer.

Tumor immune escape: extracellular vesicles roles and therapeutics application.

BACKGROUND: Immune escape, a process by which tumor cells evade immune surveillance, remains a challenge for cancer therapy. Tumor cells produce extracellular vesicles (EVs) that participate in immune escape by transferring bioactive molecules between cells. EVs refer to heterogeneous vesicles that participate in intercellular communication. EVs from tumor cells usually carry tumor antigens and have been considered a source of tumor antigens to induce anti-tumor immunity. However, evidence also suggests that these EVs can accelerate immune escape by carrying heat shock proteins (HSPs), programmed death-ligand 1 (PD-L1), etc. to immune cells, suppressing function and exhausting the immune cells pool. EVs are progressively being evaluated for therapeutic implementation in cancer therapies. EVs-based immunotherapies involve inhibiting EVs generation, using natural EVs, and harnessing engineering EVs. All approaches are associated with advantages and disadvantages. The EVs heterogeneity and diverse physicochemical properties are the main challenges to their clinical applications. SHORT CONCLUSION: Although EVs are criminal; they can be useful for overcoming immune escape. This review discusses the latest knowledge on EVs population and sheds light on the function of tumor-derived EVs in immune escape. It also describes EVs-based immunotherapies with a focus on engineered EVs, followed by challenges that hinder the clinical translation of EVs that are essential to be addressed in future investigations. Video Abstract.

Artificial Intelligence for Detection of External Cervical Resorption Using Label-Efficient Self-Supervised Learning Method.

INTRODUCTION: The aim of this study was to leverage label-efficient self-supervised learning (SSL) to train a model that can detect ECR and differentiate it from caries. METHODS: Periapical (PA) radiographs of teeth with ECR defects were collected. Two board-certified endodontists reviewed PA radiographs and cone beam computed tomographic (CBCT) images independently to determine presence of ECR (ground truth). Radiographic data were divided into 3 regions of interest (ROIs): healthy teeth, teeth with ECR, and teeth with caries. Nine contrastive SSL models (SimCLR v2, MoCo v2, BYOL, DINO, NNCLR, SwAV, MSN, Barlow Twins, and SimSiam) were implemented in the assessment alongside 7 baseline deep learning models (ResNet-18, ResNet-50, VGG16, DenseNet, MobileNetV2, ResNeXt-50, and InceptionV3). A 10-fold cross-validation strategy and a hold-out test set were employed for model evaluation. Model performance was assessed via various metrics including classification accuracy, precision, recall, and F1-score. RESULTS: Included were 190 PA radiographs, composed of 470 ROIs. Results from 10-fold cross-validation demonstrated that most SSL models outperformed the transfer learning baseline models, with DINO achieving the highest mean accuracy (85.64 ± 4.56), significantly outperforming 13 other models (P < .05). DINO reached the highest test set (ie, 3 ROIs) accuracy (84.09%) while MoCo v2 exhibited the highest recall and F1-score (77.37% and 82.93%, respectively). CONCLUSIONS: This study showed that AI can assist clinicians in detecting ECR and differentiating it from caries. Additionally, it introduced the application of SSL in detecting ECR, emphasizing that SSL-based models can outperform transfer learning baselines and reduce reliance on large, labeled datasets.

Identifying and prioritizing the key performance indicators for hospital management dashboard at a national level: Viewpoint of hospital managers.

Participation of main users in identifying key performance indicators (KPIs) for management dashboards contributes to their success. The aim of this study was to identify and prioritize the KPIs of hospital management dashboards from the viewpoint of hospital managers. This study was conducted on managers of public hospitals at a national level in Iran in 2020. Data were collected using a self-administrated questionnaire. The KPIs were classified into five categories, namely financial, operational, human resources, safety and quality of care, services provided to patients. A total of 234 hospital managers participated in this study. Totally, 25 KPIs were determined for the hospital management dashboard, including the patient falls rate, waiting time for patients in the emergency department, patient satisfaction, total hospital revenue, financial balance, bed occupancy rate, patients' discharge with own agreement, average length of stay, and personnel satisfaction. For designing hospital management dashboards, the domains of services provided to patients, safety and quality of care, financial resources, human resources, and operational are important from the hospital managers' viewpoint, respectively. The results of this study can be helpful for developers of business intelligence tools, such as hospital management dashboards, to visualize the most important indicators for managers.

Mesenchymal stem cells-derived exosomes: novel carriers for nanoparticle to combat cancer.

BACKGROUND: The advancement in novel cancer therapeutics brought a platform combining the properties of exosomes with nanoparticles to precision medicine. The novel therapeutic approach aim is cancer-targeted therapy. Exosomes from mesenchymal stem cells (MSCs-Exo) exhibit unique properties in cancer therapies, which makes them an ideal tool for delivering therapeutic agents into tumor cells. The key role of natural MSCs-Exo is controversial in cancer therapy; however, they can be engineered at their surface or cargo to serve as a smart drug delivery system for cancer-targeted therapy. In the last few years, researchers harnessed nanotechnology to enforce MSCs-Exo for cancer management including, tumor cell tracking, imaging, and tumor cell killing. Different nanoparticles such as gold nanoparticles have particularly been incorporated into MSCs-Exo, which showed an efficient accumulation at the site of tumor with improved anticancer impact. These findings indicate that a hybrid of exosomes-nanoparticles may serve as combination therapy for the effective removal of cancers. SHORT CONCLUSION: Although exhibiting impressive potential, the use of nanoparticle-loaded MSCs-Exo as a drug-delivery tool has been troubled by some challenges, therefore, translation to clinic prerequisites further scrutiny. In this review, we focus on nanoparticle-loaded MSCs-Exo as a new cancer therapy and discuss engineered MSC-Exo for target therapy.

Tumor cells-derived exosomal noncoding RNAs in cancer angiogenesis: Molecular mechanisms and prospective.

Exosomes, heterogeneous, membrane-bound nanoparticles that originated from eukaryotic cells, contribute to intracellular communication by transferring various biomolecules both on their surface and as internal cargo. One of the most significant current discussions on cancer progression is noncoding RNAs cargo of exosomes, which can regulate angiogenesis in tumor. A growing body of evidence shows that exosomes from tumor cells contain various microRNAs, long noncoding RNAs, and circular RNAs that can promote tumor progression by inducing angiogenesis. However, some noncoding RNAs may inhibit cancer angiogenesis. Targeting angiogenic noncoding RNA of exosomes may serve as a hopeful implement for cancer therapy. In this review, we discuss the latest knowledge of the roles of exosomal noncoding RNAs in tumor angiogenesis Understanding the biology of exosomal noncoding RNAs can help scientists plan exosomes-based innovations for the treatment of cancer angiogenesis and cancer biomarkers.

Structural parameters of nanoparticles affecting their toxicity for biomedical applications: a review.

Rapidly growing interest in using nanoparticles (NPs) for biomedical applications has increased concerns about their safety and toxicity. In comparison with bulk materials, NPs are more chemically active and toxic due to the greater surface area and small size. Understanding the NPs' mechanism of toxicity, together with the factors influencing their behavior in biological environments, can help researchers to design NPs with reduced side effects and improved performance. After overviewing the classification and properties of NPs, this review article discusses their biomedical applications in molecular imaging and cell therapy, gene transfer, tissue engineering, targeted drug delivery, Anti-SARS-CoV-2 vaccines, cancer treatment, wound healing, and anti-bacterial applications. There are different mechanisms of toxicity of NPs, and their toxicity and behaviors depend on various factors, which are elaborated on in this article. More specifically, the mechanism of toxicity and their interactions with living components are discussed by considering the impact of different physiochemical parameters such as size, shape, structure, agglomeration state, surface charge, wettability, dose, and substance type. The toxicity of polymeric, silica-based, carbon-based, and metallic-based NPs (including plasmonic alloy NPs) have been considered separately.

Empagliflozin Exhibits Hepatoprotective Effects Against Bile Duct Ligation-induced Liver Injury in Rats: A Combined Molecular Docking Approach to In Vivo Studies.

BACKGROUND: Cholestatic liver damage is a chronic disease caused by dysfunction of the hepaticbiliary system. Oxidative stress and inflammation are essential factors in the pathogenesis of cholestasis. Thus, the current study was designed to examine the effect of empagliflozin on bile duct ligation-induced liver damage in rats. METHODS: This study was done on male Wistar rats, which were randomly assigned to the four experimental groups: sham control (SC), bile duct ligation (BDL), SC plus empagliflozin (SC+EMPA) (receiving 10 mg of EMPA orally for 7 days), BDL plus empagliflozin 10 mg/kg (BDL+ EMPA). At the end of the study, the rats were sacrificed, and serum and tissue samples were collected to analyze biochemical parameters, biomarkers of oxidative stress, inflammatory markers, and histopathological changes. The molecular docking technique was performed to elucidate the interaction of EMPA and Cu/Zn-superoxide dismutase (SOD1). RESULTS: The results showed that BDL elevated the serum activity of ALT, AST, ALP, and levels of TBIL and TPro. BDL also intensifies the oxidative stress state in rats, which was confirmed by augmenting lipid peroxidation (MDA), protein oxidation (PCO), and altering antioxidant defense parameters through decreased SOD, catalase (CAT), and glutathione peroxidase (GPX) levels. Furthermore, the histopathological changes in the liver demonstrated the aggravation of inflammation and oxidative stress. In contrast, treatment with EMPA has shown anti-inflammatory and anti-oxidant effects by reducing TNF-α and IL-6 pro-inflammatory marker proteins, restoring the antioxidant status (increased SOD and GPX), reducing ALT, AST, ALP, TBIL levels, and protein oxidation, and improving the histopathological alterations through reducing bile duct proliferation, fibrosis, focal and portal inflammation. According to the attained findings, the SOD1 activity can be regulated by the EMPA. Our documentation presents direct evidence at the molecular level related to the ability of EMPA to exert its antioxidant performance through certain measures in a particular molecular route. CONCLUSION: The results showed EMPA to have hepatic protective effects in rats against cholestatic liver injury, an effect mediated by its antioxidant and anti-inflammatory properties.

SE-ECL on CMOS: a miniaturized electrochemiluminescence biosensor.

Biosensors exhibit high potential for the detection of analytes of interest at the point-of-need. Over the past two decades, the combination of novel biosensing systems - such as electrochemiluminescence (ECL) biosensors - and advances in microfluidic techniques has allowed the development of lab-on-a-chip devices with enhanced overall performance and simplified sample handling. However, recording data with conventional platforms requires advanced and complicated instruments, such as sensitive photodetectors coupled to microscopes, to capture the photons from the chemiluminescent reaction. In this work, we integrated microfluidic and luminol/hydrogen peroxide ECL systems on a complementary metal-oxide-semiconductor (CMOS) chip for sample handling and data collection on the same platform. This was achieved by the adaptation of a single electrode as an electrochemical transducer and a CMOS chip as a built-in detector. We demonstrated the application of this platform for the detection of uric acid (UA), a biomarker of gout disease. A linear detection range was observed from 25 to 300 µM, with a detection limit (LOD) as low as 26.09 µM. The device showed high reusability and reproducibility within the linear detection range while maintaining high selectivity for UA detection. The analytical performance has also been evaluated in simulated saliva and urine samples, demonstrating the potential utility in medical diagnosis at the point-of-need. Compared to other ECL imaging platforms, this device showed an eightfold increase in photon collection efficiency. Overall, this approach has promising potential as an inexpensive, portable, and efficient ECL platform for measuring analytes at the point-of-need.

Management of pleural empyema in a 12-year-old obese patient with COVID-19: a pediatric case report.

BACKGROUND: With the ongoing coronavirus disease (COVID-19) pandemic, along with the development of new mutations of the virus and an increase in the number of cases among pediatrics, physicians should be aware and alerted on the atypical presentations of the disease, especially in less expected individuals. CASE PRESENTATION: Here we present a 12-year-old obese boy (BMI = 37.5 kg/m2) who presented with empyema, which was following SARS-CoV-2 infection. The patient had no history of fever. Due to the onset of dyspnea, a chest tube was inserted for him which was later altered to a pleural drainage needle catheter. CONCLUSION: Our case is the first report of COVID-19 presenting as empyema among pediatrics. Pleural empyema should be considered as a rare complication of COVID-19. Since there is still no guideline in the management of empyema in the context of COVID-19, delay in diagnosis and intervention may cause morbidity and mortality in children.

Confidentiality of Information Stored on the Desktop of Computers in a Psychiatric Hospital: Before and After an Intervention.

The aim of this before-after study was to evaluate the effect of an educational intervention on the confidentiality status of unprotected information stored on computer desktop in a psychiatric hospital. All switched-on computer systems were inspected in 2017-2018 at the baseline and 7 months after placing an educational poster. The log-in conditions and files stored on the desktop were reviewed using a researcher-made checklist; moreover, users answered questions about the possible mechanism of deleting information stored on the desktop. The number of files stored on desktops, the number of systems left switched on and unused, and the number of systems without a log-in password decreased in the second phase than the first phase of this study. Furthermore, automatic locking of computers after a specified period increased. The educational intervention reduced significantly the storage of information on desktops and improved security mechanisms such as using passwords and autolock. This study showed using an educational poster can encourage users to preserve the security of information, comply with security guidelines such as locking unused computers, and prevent access to confidential information.

Protective and therapeutic effects of ethanolic extract of Nasturtium officinale (watercress) and vitamin E against bleomycin-induced pulmonary fibrosis in rats.

BACKGROUND AND PURPOSE: Pulmonary fibrosis is a chronic disease of the lungs caused by inflammation, species of reactive oxygen, and immune defects. Antioxidant properties of Nasturtium officinale has been reported in some studies. Therefore, the objective of the current study was to evaluate the effect of ethanolic extract of Nasturtium officinale (EENO) on bleomycin (BLM)-induced lung fibrosis in rats. EXPERIMENTAL APPROACH: Forty adult male Wistar rats (180-220 g) were randomly divided into 5 experimental groups. Normal control, BLM control received a single dose of BLM (6 IU/kg) intratracheally only on the first day, EENO + BLM group received EENO (500 mg/kg) one week before intratracheal BLM instillation and two weeks afterward, BLM + EENO group and BML + vitamin E group received EENO (500 mg/kg) and vitamin E (500 mg/kg) half-hour after BLM installation, respectively. The animals were sacrificed on day 22. Change in body weight, lung index, serum level of malondialdehyde (MDA) and nitric oxide (NO) metabolite, lung tissue hydroxyproline content and lung pathology were assessed. FINDINGS/RESULTS: Pre- or post-treatment with EENO attenuated pulmonary fibrosis as evidenced by normalized lung index, improved histological changes and inhibited collagen deposition (hydroxyproline) in the animal lung. EENO also decreased MDA and NO metabolite release in comparison to the BLM control. vitamin E (500 mg/ kg) also significantly inhibited the BLM-induced lung toxicity. CONCLUSIONS AND IMPLICATIONS: EENO can prevent BLM-induced lung fibrosis in rats via antioxidant activities. However, more studies are needed to elicit the exact mechanism of this effect.

Iron oxide and gold bimetallic radiosensitizers for synchronous tumor chemoradiation therapy in 4T1 breast cancer murine model.

The development of highly integrated multifunctional nanomaterials with a superadditive therapeutic effect and good safety is an urgent but challenging task in cancer therapy research. The present study aims to design a nanoplatform that offers the opportunity to enhance antitumor activity while minimizing side effects. Given the Au-mediated X-ray radiation enhancement and the ability of Fe-based nanomaterials to create reactive oxygen species (ROS) and DNA damage, we anticipated that bimetallic Fe3O4-Au heterodimer would bring strong radiosensitizing capacity. Fe3O4-Au heterodimer surface was covered with bovine serum albumin (BSA) to achieve good surface functionality, stability and prolonged blood circulation. Folic acid (FA) moieties were added to the nanoformulation to increase tumor-homing, specificity and uptake. Finally, curcumin (CUR) was incorporated into the nanoparticle to function as a natural anticancer agent. The integration of all these components has yielded a single nanoplatform, Fe3O4-Au-BSA-FA-CUR, capable of successfully fulfilling the mission of superadditive cancer therapy to avoid the risks of organ removal surgery. The efficacy of the proposed nanoplatform was investigated in vitro and in vivo. High radiosensitizing ability, X-ray-induced ROS generation and DNA damage, and good biocompatibility were demonstrated through in vitro experiments. Also, the administration of Fe3O4-Au-BSA-FA-CUR with X-ray irradiation completely eradicated the tumor without any mortality and toxicity in healthy tissues in vivo. Our results highlight the potential of CUR-loaded Fe3O4-Au-BSA-FA heteronanostructure to enable synergistic localized radiochemotherapy and open up a new door to attractive possibilities that warrant further exploration.

Evaluating physicians' perspectives on the efficiency and effectiveness of the electronic prescribing system.

BACKGROUND: The implementation of the electronic prescribing system follows certain objectives, and users' perspectives can contribute to understanding the efficiency and effectiveness of this system. This study aimed to evaluate physicians' perspectives on the efficiency and effectiveness of the electronic prescribing system. METHODS: This study was conducted on all physicians using the electronic prescribing system in clinics and hospitals affiliated with the treatment deputy of the Social Security Organization (SSO) in Sistan and Baluchistan Province in Iran. Data were collected using a self-administered questionnaire containing three sections: (i) Six items related to demographic data and clinical experience, (ii) Specific questions based on a five-point Likert scale-related physicians' perspectives about efficiency (19 questions) and effectiveness (13 questions), and (iii) Open-ended questions about the positive and negative aspects of using the electronic prescribing system. RESULTS: The mean and standard deviation of the efficiency and effectiveness of the electronic prescribing system were 3.68 ± 0.67 and 3.84 ± 0.65, respectively. Patient safety had the highest mean score among all dimensions (4.0 ± 0.64). Most participants (n = 55, 79%) considered the efficiency and effectiveness of this system high. More than 90 percent of the physicians (n = 63) believed that the electronic prescribing system enables a better medication prescription by providing alerts and access to patients' medication history. CONCLUSION: The findings showed that most physicians believed that the electronic prescribing system of Iran's SSO has high efficiency and effectiveness. In particular, physicians believed that using this system improves patient safety and reduces costs.

Antibiotic prescribing in inpatient and outpatient settings in Iran: a systematic review and meta-analysis study.

BACKGROUND: Antibiotic prescribing is common worldwide. There are several original studies about antibiotic prescribing in the healthcare setting of Iran reporting different levels of prescribing. The aim of this systematic review and meta-analysis was to determine the prevalence of antibiotic prescribing in both inpatient and outpatient settings in Iran, an example of a developing country. METHODS: To identify published studies on antibiotic prescribing, databases such as ISI, Scopus, PubMed, Google Scholar, and Electronic Persian were searched in Iran till January 2020. Eligible studies were those analyzing original data on the prescription and use of antibiotics in outpatient or inpatient settings in Iran. Moreover, all studies that used an intervention to improve antibiotic prescribing were included. The quality of the included studies was assessed using self-administered quality assessment criteria. The meta-analysis of prevalence of antibiotic prescribing was conducted based on the meta-analysis of observational studies in epidemiology guidelines. To calculate pooled rates, the random-effects model was used. RESULTS: A total of 54 studies (39 outpatients and 15 inpatients) were included in this study. The median of antibiotic prescribing in the outpatient and inpatient settings accounted for 45.25% and 68.2% of patients, respectively. The results of meta-analysis also showed that the antibiotic prescribing accounted for 45% of prescriptions in outpatient settings and 39.5%, 66%, and 75.3% of patients in all wards, pediatrics wards, and ICU wards of inpatient settings, respectively. The most commonly prescribed antibiotic classes in outpatient settings were penicillins, cephalosporins, and macrolides, while in inpatient settings, these were cephalosporins, penicillins, and carbapenems. There were seven studies using interventions to improve antibiotic prescribing pattern. It should be mentioned that intervention in a study had a statistically significant effect on improving antibiotic prescribing (p < .05). CONCLUSION: Prevalence of antibiotic prescribing in Iran is high. Our findings highlight the need for urgent action to improve prescription practices. It seems that developing a national plan to improve antibiotic prescribing is necessary.

Major dietary patterns in relation to preeclampsia among Iranian pregnant women: a case-control study.

BACKGROUND: Preeclampsia is a pregnancy disorder that increases the risk of prenatal and maternal complications. Therefore, prevention of preeclampsia requires identifying its preventable risk factors such as dietary patterns. OBJECTIVE: This study aimed to investigate the relationship between the major dietary patterns and preeclampsia. STUDY DESIGN: In this case-control study, the dietary patterns of a total of 510 pregnant women were investigated. Data on their dietary intake, sociodemographics, and daily physical activity levels were collected using a 198 item semi-quantitative food frequency questionnaire, a sociodemographic questionnaire, and a physical activity questionnaire, respectively. To identify the major dietary patterns and to model the relationship between dietary patterns and preeclampsia, factor analysis and unconditional logistic regression were employed, respectively. The three major dietary patterns identified were as follows: healthy dietary pattern (i.e. high in fruits, low-fat dairy, dried fruits, nuts, vegetables, fruit juice, liquid oil, and tomatoes), western dietary pattern (i.e. high in red meat, processed meat, fried potatoes, and pickles), and Iranian traditional dietary pattern (i.e. high in eggs, potatoes, and legumes). RESULTS: After adjustment for confounding factors, we found that with an increase in the healthy dietary pattern score, the odds of preeclampsia were reduced to 87.5% (OR = 0.125, 95%CI: 0.070-0.221, p < .001); with an increase in the western dietary pattern score, the odds of preeclampsia were increased 5.99 times (OR = 5.99, 95%CI: 3.414-10.53, p < .001); and with an increase in the Iranian traditional dietary pattern score, the odds of preeclampsia were reduced to 81.7% (OR = 0.183, 95%CI: 0.109-0.308, p < .001). CONCLUSION: The findings showed that the western dietary pattern had a direct relationship and the healthy and Iranian traditional patterns had a reverse relationship with preeclampsia.

mTOR-Mediated Regulation of Immune Responses in Cancer and Tumor Microenvironment.

The mechanistic/mammalian target of rapamycin (mTOR) is a downstream mediator in the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathways, which plays a pivotal role in regulating numerous cellular functions including cell growth, proliferation, survival, and metabolism by integrating a variety of extracellular and intracellular signals in the tumor microenvironment (TME). Dysregulation of the mTOR pathway is frequently reported in many types of human tumors, and targeting the PI3K/Akt/mTOR signaling pathway has been considered an attractive potential therapeutic target in cancer. The PI3K/Akt/mTOR signaling transduction pathway is important not only in the development and progression of cancers but also for its critical regulatory role in the tumor microenvironment. Immunologically, mTOR is emerging as a key regulator of immune responses. The mTOR signaling pathway plays an essential regulatory role in the differentiation and function of both innate and adaptive immune cells. Considering the central role of mTOR in metabolic and translational reprogramming, it can affect tumor-associated immune cells to undergo phenotypic and functional reprogramming in TME. The mTOR-mediated inflammatory response can also promote the recruitment of immune cells to TME, resulting in exerting the anti-tumor functions or promoting cancer cell growth, progression, and metastasis. Thus, deregulated mTOR signaling in cancer can modulate the TME, thereby affecting the tumor immune microenvironment. Here, we review the current knowledge regarding the crucial role of the PI3K/Akt/mTOR pathway in controlling and shaping the immune responses in TME.

In vitro and in vivo activity of cinnamaldehyde against Eimeria kofoidi in chukar partridge (Alectoris chukar).

One hundred and twenty one-day-old chukar partridges were randomly divided into eight groups which received diets with different supplementations. There were four unchallenged groups. One group received salinomycin (50 ppm), two groups received cinnamaldehyde (CINN) (100 and 200 mg/kg of diet), and another one received only the basal diet from the 1st to the 31st day. There were also four corresponding groups orally challenged by 3 × 105Eimeria kofoidi sporulated oocysts at the 21st day. Three samplings were done at the 24th, 26th, and 31st days of rearing for pathological and biochemical assessments. Fecal samples were daily taken to check the pattern of oocyst shedding from the 26th to 31st day. The body weight of birds was measured at 21st and 31st days. Along with the in vivo experiment, an in vitro sporulation inhibition test was carried out. The in vitro results showed that CINN decreased sporulation rate at 1 and 0.5 mg/ml. In vivo, it was found that CINN did not prevent the oocyst shedding. Furthermore, the histopathological findings revealed that CINN and salinomycin had no effect on infection establishment. However, our findings showed that CINN (200 mg/kg of diet) could enhance the body weight and improve antioxidant status. Although our results did not support the in vivo anticoccidial activity of CINN, it had a promising potential to improve antioxidant status and body weight in the chukar partridge.