Integrated neural network and evolutionary algorithm approach for liver fibrosis staging: Can artificial intelligence reduce patient costs?

Background and Aim: Staging liver fibrosis is important, and liver biopsy is the gold standard diagnostic tool. We aim to design and evaluate an artificial neural network (ANN) method by taking advantage of the Teaching Learning-Based Optimization (TLBO) algorithm for the prediction of liver fibrosis stage in blood donors and hepatitis C patients. Methods: We propose a method based on a selection of machine learning classification methods including multilayer perceptron (MLP) neural network, Naive Bayesian (NB), decision tree, and deep learning. Initially, the synthetic minority oversampling technique (SMOTE) is performed to address the imbalance in the dataset. Afterward, the integration of MLP and TLBO is implemented. Results: We propose a novel algorithm that reduces the number of required patient features to seven inputs. The accuracy of MLP using 12 features is 0.903, while that of the proposed MLP with TLBO is 0.891. Besides, the diagnostic accuracy of all methods, except the model designed with the Bayesian network, increases when the SMOTE balancer is applied. Conclusion: The decision tree-based deep learning methods show the highest levels of accuracy with 12 features. Interestingly, with the use of TLBO and seven features, MLP reached an accuracy rate of 0.891, which is quite satisfactory when compared with those of similar studies. The proposed model provides high diagnostic accuracy, while reducing the required number of properties from the samples. The results of our study show that the recruited algorithm of our study is more straightforward, with a smaller number of required properties and similar accuracy.

Aluminium Nanoparticles as Efficient Adjuvants Compared to Their Microparticle Counterparts: Current Progress and Perspectives.

Aluminium (Al) compounds are used as adjuvants in human and veterinary prophylactic vaccines due to their improved tolerability compared to other adjuvants. These Al-based adjuvants form microparticles (MPs) of heterogeneous sizes ranging from ~0.5 to 10 µm and generally induce type 2 (Th2)-biased immune responses. However, recent literature indicates that moving from micron dimension particles toward the nanoscale can modify the adjuvanticity of Al towards type 1 (Th1) responses, which can potentially be exploited for the development of vaccines for which Th1 immunity is crucial. Specifically, in the context of cancer treatments, Al nanoparticles (Al-NPs) can induce a more balanced (Th1/Th2), robust, and durable immune response associated with an increased number of cytotoxic T cells compared to Al-MPs, which are more favourable for stimulating an oncolytic response. In this review, we compare the adjuvant properties of Al-NPs to those of Al-MPs in the context of infectious disease vaccines and cancer immunotherapy and provide perspectives for future research.

Dual role of microRNA-1297 in the suppression and progression of human malignancies.

MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded and tiny RNAs that modulate several biological functions, more importantly, the pathophysiology of numerous human cancers. They are bound with target mRNAs and thereby regulate gene expression at post-transcriptional levels. MiRNAs can either trigger cancer progression as an oncogene or alleviate it as a tumor suppressor. Abnormal expression of microRNA-1297 (miR-1297) has been noticed in several human cancers suggesting a distinct role for the miRNA in tumorigenesis. More specifically, it is both up-regulated and down-regulated in various cancers suggesting that it can act as both tumor suppressor and oncogene. This review systematically highlights the different roles of miR-1297 in the pathophysiology of human cancers, explains the mechanisms underlying miR-1297-mediated tumorigenesis, and discusses its potential prognostic, diagnostic, and therapeutic importance.

Evaluation of local and circulating osteopontin in malignant and benign primary bone tumors.

PURPOSE: The development of novel and efficient biomarkers for primary bone cancers is of grave importance. METHODS: The expression pattern of osteopontin (OPN) was investigated in the 153 patients with benign (n = 72) and malignant (n = 81) primary bone cancers. Both local and circulating OPN mRNA expression levels and their protein concentration in serum and tumor site were assessed using real-time qRT-PCR, ELISA, and immunohistochemistry techniques, respectively. As a control, 29 healthy individuals were considered. The number of 153 tumor tissue specimens and the 153 paired margins were taken on surgical resection from the patients. 153 blood samples were also drained from all participants, then peripheral blood mononuclear cells (PBMC) and sera were separated. RESULTS: The mean mRNA expression was significantly higher in all of the cancerous tissues than the paired margins and the PBMC of the patients than the controls. Consistently, the protein concentrations of OPN in serum and tumor tissues were significantly higher in the patients. Furthermore, the malignant cases had significantly elevated the mRNA levels and the protein compared to the benign cases. OPN could potentially differentiate the patients from the controls with 100% sensitivity and specificity in serum. Moreover, OPN could predict some of the malignant cases' clinicopathological features, including metastasis, recurrence, grade, and response to chemotherapy. CONCLUSIONS: In conclusion, OPN might be involved in the pathogenesis of primary bone tumors and can be considered as a potential biomarker to bone cancer diagnosis.

MiR-613 Promotes Cell Death in Breast Cancer Cells by Downregulation of Nicotinamide Phosphoribosyltransferase and Reduction of NAD.

NAD is mainly biosynthesized by the enzymatic action of nicotinamide phosphoribosyltransferase (NAMPT) through the salvage pathway. NAD is indispensable for the proper function and metabolism of all living cells, including cancer cells. Our previous researches revealed that inhibition of NAMPT by miRNA (miR) could suppress NAD levels and thereby hinder the growth and promotion of breast cancer (BC). Therefore, the current study was undertaken to investigate the inhibitory effects of miR-613 on NAMPT and BC cells' survival. Bioinformatics analysis and luciferase reporter assay confirmed that NAMPT 3'-untranslated region is a direct target for miR-613. The expression of miR-613 was noticed to be significantly decreased in both clinical tissue samples and BC cells by real-time PCR. Following transfection with miR-613 mimic, the expression of miR-613 was elevated in the BC cells leading to inhibition of NAMPT expression at both mRNA and protein level as measured by real-time PCR and western blotting, respectively. Inhibition of NAMPT led to a remarkable reduction in the concentration of NAD in the BC cells. The transfection also declined cell viability roughly 40% in MD Anderson-Metastatic Breast-231 (MDA-MB-231) cells. Consistently, the apoptosis rate was remarkably increased, around 65% in these cells as assayed by labeling the cells with Annexin V-fluorescein isothiocyanate (FITC) and Propidium Iodide. Targeting the NAMPT-mediated NAD salvage pathway by miR-613 is a novel approach for managing BC, which is worth further investigation.

Effects of Securigera securidaca (L.) Degen & Dorfl seed extract combined with glibenclamide on paraoxonase1 activity, lipid profile and peroxidation, and cardiovascular risk indices in diabetic rats.

Introduction: Seeds of Securigera securidaca (L.) Degen & Dorfl are rich in flavonoids and phenolic acids which have potent biological effects. The current study was undertaken to evaluate the effects of hydroalcoholic extract of S. securidaca seeds (HESS) alone, and in combination with a standard drug, glibenclamide (GB) on paraoxonase1 (PON1) activity, lipid profile and peroxidation, and cardiovascular risk indices in streptozotocin (STZ) induced diabetic rats. Methods: Forty-eight male Wistar rats were randomly divided into eight equal groups and orally treated with various doses of HESS (100, 200, 400 mg/kg) alone and in combination with GB (5 mg/kg) for 35 consecutive days. After blood sampling, lipid profile including triglyceride (TG), cholesterol, high, low and very low-density lipoprotein-cholesterol (HDL-C, LDL-C, and VLDL-C), as well as serum PON1 activity, were assessed. Malondialdehyde (MDA), tumor necrosis factor-alpha (TNF-α), and high-sensitivity C-reactive protein (hs-CRP) levels were also measured. Several indices of cardiovascular risk and the correlation between PON1 activity and these indices were calculated based on the obtained results from the lipid profile. Results: Induction of diabetes could dramatically alter all of the parameters mentioned above, and the lower dose of HESS (100 mg/kg) was not effective in restoring the parameters. However, the higher doses (200 and 400 mg/kg) alone and in combination with GB could significantly improve lipid profile, restore PON1 activity, and decrease cardiovascular risk indices, MDA, as well. However, neither HESS nor GB could significantly reduce TNF-α and hs-CRP. A significant negative correlation also was detected between PON1 activity and cardiovascular risk indices. Conclusion: conclusively, HESS can be considered as a potent antihyperlipidemic agent with remarkable cardioprotective effects and can potentiate the antidiabetic effects of GB.

MicroRNA-154: A Novel Candidate for Diagnosis and Therapy of Human Cancers.

MicroRNAs (miRNAs) are endogenous, non-coding, single-stranded, tiny RNAs with 21-23 nucleotides that regulate several biological functions through binding to target mRNAs and modulating gene expression at post-transcriptional levels. Recent studies have described crucial roles for miRNAs in pathophysiology of numerous human cancers. They can act as an oncogene and promote cancer or as a tumor suppressor and alleviate the disease. Recently discovered microRNA-154 (miR-154) has been proposed to be involved in multiple physiological and pathological processes including cancer. With this aspect, aberrant expression of miR-154 has been demonstrated in variety of human malignancies, suggesting an important role for miR-154 in tumorigenesis. To be specific, it is considered as a tumor suppressor miRNA and exerts its beneficial effects by targeting several genes. This review systematically summarizes the recent advances done on the role of miR-154 in different cancers and discusses its potential prognostic, diagnostic and therapeutic values.

Small dense low-density lipoprotein-lowering agents.

Metabolic disorders, including obesity, diabetes, and hyperlipidemia, as well as cardiovascular diseases (CVD), particularly atherosclerosis, are still leading causes of death worldwide. Plasma levels of low-density lipoprotein (LDL) are currently being considered as a critical risk factor for the diseases mentioned above, especially atherosclerosis. Because of the heterogeneous nature of LDL, many studies have already been conducted on its subclasses, especially small dense LDL (sdLDL). According to available evidence, sdLDL levels can be considered as an ideal alternative to LDL levels for monitoring CVD and early diagnosis of atherosclerosis. Recently, several researchers have focused on factors that are able to decrease sdLDL levels and improve health quality. Therefore, the purpose of this study is to describe the production process of sdLDL particles and review the effects of pharmaceutical and dietary agents as well as lifestyle on sdLDL plasma levels. In brief, their mechanisms of action are discussed. Apparently, cholesterol and LDL-lowering compounds are also effective in the reduction of sdLDL levels. In addition, improving lipid profile, especially the reduction of triglyceride levels, appropriate regimen, and lifestyle can decrease sdLDL levels. Therefore, all the aforementioned parameters should be taken into consideration simultaneously in sdLDL levels reducing strategies.

Effects of Securigera Securidaca seed extract in combination with glibenclamide on antioxidant capacity, fibroblast growth factor 21 and insulin resistance in hyperglycemic rats.

ETHNOPHARMACOLOGICAL RELEVANCE: Undesired effects of synthetic antidiabetic agents have made researchers to seek for safer and healthier resources. With this aspect, herbal materials have attracted substantial research interest and are being extensively investigated. Considering that herb-drug interactions can be a double-edged sword presenting both risks and benefits, investigation of such interactions is greatly in demand. AIM OF THE STUDY: to investigate possible beneficial effects of hydroalcoholic extract of SecurigeraSecuridaca seed (HESS) on antioxidant capacity, fibroblast growth factor 21 (FGF21) and insulin resistance in Streptozotocin (STZ)-induced diabetic rats, alone and in combination with glibenclamide. MATERIALS AND METHODS: Forty male Wistar rats were randomly divided in to eight equal groups including healthy and diabetic controls and six treated groups with a various doses of HESS alone and in combination with glibenclamide, for 35 consecutive days. Serum samples were taken and analyzed for biochemical profile, HOMA indexes, FGF21, oxidative/nitrosative stress and inflammatory biomarkers as compared with the controls. Moreover, total phenolic and flavonoid contents of herbal extract were assessed. RESULTS: The herbal extract was found to be rich in flavonoid and phenolic components. Both of glibenclamide and the HESS decreased glucose and insulin resistance, as well as increased body weight and insulin sensitivity. Moreover, the extract could mitigate oxidative/nitrosative stress and inflammation dose-dependently, however, the standard drug was less effective than HESS. Induction of diabetes increased FGF21 levels and both of the treatments could reduce its contents, however, glibenclamide was more effective than HESS. CONCLUSIONS: The results clearly show that there is no contradiction between HESS and glibenclamide. Moreover, the herbal extract could augment antioxidant and anti-inflammatory properties of the standard drug.

Selenium supplementation in the form of selenium nanoparticles and selenite sodium improves mature male mice reproductive performances.

OBJECTIVES: The current study was conducted to examine the possible protective and retentive effects of one-week intra-peritoneal (IP) administration of selenium nanoparticles (Se-NPs), compared to its bulk counterpart, selenite sodium (Ss), after one complete cycle of spermatogenesis in mature male mice. MATERIALS AND METHODS: Thirty adult male mice were divided into 3 groups. Control group was administrated phosphate-buffered saline (IP) and the other groups received Ss (0.50 mg kg-1) and Se-NPs (0.50 mg kg-1) for seven successive days. Then, the animals were monitored for 28 days and finally sacrificed and tissue and blood samples were taken. Histopathological features, sperm quality, in vitro fertilization (IVF) capability and selenium (Se) content in testicular tissue were analyzed. Antioxidant enzyme activities including catalase, glutathione peroxidase, and superoxide dismutase as well as total antioxidant capacity and malondialdehyde levels were assessed in blood and the tissue samples. RESULTS: Remarkable differences were found in sperm characteristics, histopathological features and oxidative stress biomarkers between control and treatment groups. Moreover, IVF evaluation and tissue Se concentration examination weren't similar for Se-NPs and Ss. CONCLUSION: Conclusively, Se-treated groups had more antioxidant capacity than the control group, but sperm quality and histopathological features revealed that Se-NPs might possess more antioxidative and retentive potential compared to Ss in one spermatogenesis cycle.

Comparative study of radioprotective effects of selenium nanoparticles and sodium selenite in irradiation-induced nephropathy of mice model.

PURPOSE: The current study was undertaken to evaluate radioprotective effects of selenium (Se) nanoparticles in irradiation-induced nephropathy of mice model compared to sodium selenite. MATERIALS AND METHODS: Forty-five mice were divided into three major groups including control, Se nanoparticle, and sodium selenite. Each major group was further subdivided into three more groups receiving various doses of 0, 2, and 8 Gy gamma irradiation. Both of the supplements were administered intraperitoneally with the dose of 0.1 mg/kg for 14 consecutive days. At the end of each week, the animals were exposed to gamma radiation and 48 h after the last exposure, the animals were humanely euthanized, then blood and renal tissue samples were taken. Serum creatinine, urea, cystatin C, and beta-2-microglobulin levels as well as activities of renal antioxidant enzymes, superoxide dismutase, glutathione peroxidase and catalase, also malondialdehyde level, total antioxidant capacity, renal tissue Se content, and histopathological features were assessed. RESULTS: The results showed that both of the supplements could normalize aforementioned indices. However, selenium nanoparticles (Se-NPs) were more effective than sodium selenite. CONCLUSIONS: Conclusively, Se-NPs as an emerging potent antioxidant agent can protect against irradiation-induced nephropathy.

Comparative study of cardio-protective effects of zinc oxide nanoparticles and zinc sulfate in streptozotocin-induced diabetic rats.

The cardio-protective effects of zinc oxide nanoparticles (Zn NPs) against diabetes-induced cardiopathy were evaluated and compared with zinc sulfate (ZnSO4). A total of 120 Wistar rats were randomly categorized as healthy and diabetic groups. Then, the 2 groups were classified in 5 subgroups. The animals received oral supplementations containing different Zn NP (ie, doses of 1, 3, and 10mg/kg) and ZnSO4 (30mg/kg) concentrations over 8 weeks. Blood and cardiac tissue samples were collected in the different time intervals and subjected to biochemical and histopathological analysis. Zn NPs showed dual effects, as its middle dose played protective role and recovered cardiac damages evidenced by significant reduction of serum cholesterol, HDL-cholesterol, lipoprotein (a), atherogenic index, TNF-α, cardiac MDA, B-type natriuretic peptide and caspase-3 activity. Apoptosis indices and histopathological features also were improved. However, the highest dose was found to be toxic and resulted in aggravation of the injuries. Another interesting finding is the ability of the higher doses of Zn-NPs (3 and 10mg/kg) to elevate cardiac zinc levels above the normal range in healthy animal. ZnSO4 also helped to recuperation of the damages, but the middle dose of Zn NPs was more efficient as compared to ZnSO4. Conclusively, Zn NPs have the potential for Zn delivery in diabetic patients.

Comparative Study of Antidiabetic Activity and Oxidative Stress Induced by Zinc Oxide Nanoparticles and Zinc Sulfate in Diabetic Rats.

In the current study, antidiabetic activity and toxic effects of zinc oxide nanoparticles (ZnO) were investigated in diabetic rats compared to zinc sulfate (ZnSO4) with particular emphasis on oxidative stress parameters. One hundred and twenty male Wistar rats were divided into two healthy and diabetic groups, randomly. Each major group was further subdivided into five subgroups and then orally supplemented with various doses of ZnO (1, 3, and 10 mg/kg) and ZnSO4 (30 mg/kg) for 56 consecutive days. ZnO showed greater antidiabetic activity compared to ZnSO4 evidenced by improved glucose disposal, insulin levels, and zinc status. The altered activities of erythrocyte antioxidant enzymes as well as raised levels of lipid peroxidation and a marked reduction of total antioxidant capacity were observed in rats receiving ZnO. ZnO nanoparticles acted as a potent antidiabetic agent, however, severely elicited oxidative stress particularly at higher doses.

Congenital multi-organ malformations in a Holstein calf.

A 5-day-old female Holstein calf was necropsied because of lethargy, recumbency and anorexia. At necropsy, multiple gross defects were evident in several organs, including unclosed sutures of skull bones, asymmetrical orbits, doming of the skull bones, hydrocephalus, hydranencephaly, cleft palate, brachygnathia, ventricular septal defect, mitral valve dysplasia and rudimentary lungs. On microscopic examination, pulmonary hypoplasia was characterized by reduced number of alveoli, replacement of peri-bronchiolar smooth muscles with connective tissue and small masses of undeveloped cartilage around the small airways. The present report is the first description of the congenital pulmonary hypoplasia accompanied by numerous malformations in Holstein breed.

Hydro-alcoholic extract of Raphanus sativus L. var niger attenuates bleomycin-induced pulmonary fibrosis via decreasing transforming growth factor ß1 level.

Pulmonary fibrosis is a progressive disease of the lungs, which leads to death in human. It has been suggested that transforming growth factor beta 1 (TGF-ß1) together with oxidative stress play a central role in the pathogenesis of the ailment. The objective of this study was to evaluate the possible curative effects of black radish, Raphanus sativus L. var niger (RSN) on bleomycine (BLM) -induced pulmonary fibrosis in a rat model. In this study, thirty-six male Wistar rats were divided into six groups, including: (I) positive (BLM) control group, (II) negative (normal saline) control group, (III) sham group (R. sativus extract 150 mg/kg), and (IV-VI) treatment groups. In order to induce pulmonary fibrosis, four groups were treated with a single dose of BLM sulfate (7.5 U/kg) through intratracheal instillation. Treatment groups (IV-VI) received RSN extract (75, 150, and 300 mg/kg) orally a week before and two weeks after the administration of BLM. At the end of the treatment course, blood and lung tissue samples were taken and the measurement of TGF-ß1 and histopathological examination of the lung tissues performed. The results showed that RSN, at 300 mg/kg dose, could significantly decrease the serum level of TGF-ß1 and severity of the histological lesions as compared to the positive control group. The results of the current study indicate that the components present in the extract can remarkably prevent the aggravation of pulmonary fibrosis via decreasing TGF-ß1 level.

Early stage of acute coenurosis in Iranian native sheep- case report.

Cerebral coenurosis is the intermediary larval stage of Taenia multiceps, which affects intermediate hosts, particularly sheep and goats. In this report, gross and microscopic features of three scarce natural coenurosis cases, a one-year-old ram and two lambs of 7 month old from a flock are explained. At necropsy, numerous small cysts measuring 5 to 10 mm in diameter were observed on both cerebrum and cerebellum surfaces, likewise multiple deep parts of which. In histopathological examination of the neural tissue, severe tissue destruction, a distinct layer of Gitter cells formation around the cysts, neuronophagia, gliosis and perivascular infiltration of lymphocytes were observed. In this early stage of parasite life cycle, larval migration and destruction of tissue, also aggregation of glial cells around the cysts cause a loose connection between cysts and neural tissue.