Joint MAPLE: Accelerated joint T1 and T 2 * $$ {{\mathrm{T}}_2}

PURPOSE: Quantitative MRI finds important applications in clinical and research studies. However, it is encoding intensive and may suffer from prohibitively long scan times. Accelerated MR parameter mapping techniques have been developed to help address these challenges. Here, an accelerated joint T1, T 2 * $$ {{\mathrm{T}}_2}^{\ast } $$ , frequency and proton density mapping technique with scan-specific self-supervised network reconstruction is proposed to synergistically combine parallel imaging, model-based, and deep learning approaches to speed up parameter mapping. METHODS: Proposed framework, Joint MAPLE, includes parallel imaging, signal modeling, and data consistency blocks which are optimized jointly in a combined loss function. A scan-specific self-supervised reconstruction is embedded into the framework, which takes advantage of multi-contrast data from a multi-echo, multi-flip angle, gradient echo acquisition. RESULTS: In comparison with parallel reconstruction techniques powered by low-rank methods, emerging scan specific networks, and model-based T 2 * $$ {{\mathrm{T}}_2}^{\ast } $$ estimation approaches, the proposed framework reduces the reconstruction error in parameter maps by approximately two-fold on average at acceleration rates as high as R = 16 with uniform sampling. It can outperform evaluated parallel reconstruction techniques up to four-fold on average in the presence of challenging sub-sampling masks. It is observed that Joint MAPLE performs well at extreme acceleration rates of R = 25 and R = 36 with error values less than 20%. CONCLUSION: Joint MAPLE enables higher fidelity parameter estimation at high acceleration rates by synergistically combining parallel imaging and model-based parameter mapping and exploiting multi-echo, multi-flip angle datasets. Utilizing a scan-specific self-supervised reconstruction obviates the need for large data sets for training while improving the parameter estimation ability.

Zoning of some physicochemical parameters in the sediments of Meighan wetland in Iran: response to urbanization, industrial, and agricultural activities.

Meighan wetland is located at 8 km far away from Arak city with a population of about 600,000 citizens in the center of Iran. Several agricultural activities and industries such as metal, chemical, and mineral, as well as industrial towns, exist around the desired wetland. This research was conducted to measure the sources of chemical contaminants entering the wetland through natural and artificial waterways, to explore the trend of changes in the contaminants, and to prepare the wetland contamination zone map followed by source detection of these contaminants. Sediment samples were taken during 2019-2020 from a depth of 0-30 cm from 87 points in the input waterways. The results indicated that the mean total concentrations of cadmium, nickel, lead, zinc, copper, and aluminum in sediments were estimated as 6.7, 93.4, 14.1, 276.4, 34.3, and 22,742.7 ppm, respectively. The concentrations of nitrate and phosphate in the sediments were given as 18.6 and 1.8 ppm, respectively. The mean comparison indicated that the most significant level of nickel and lead belonged to the input waterways of industrial and urban regions; the maximum cadmium content was seen in the input waterways from the agricultural lands; and the highest level of zinc and aluminum was recorded in the waterways of agricultural-industrial urban regions. There was a significant relationship between the results of classic statistics and zoning found in GIS. Overall, chemical pollutants with the origin of input wastewater from the treatment plant of wastewater and the input waterways from the industrial and urban regions have had the largest share of contamination for Meighan wetland.

The effects of environmental factors on plant diversity of Darab natural ecosystems in Fars province, Iran.

This research quantitatively evaluated the diversity of plants to protect vulnerable species. To measure vegetation information, the appropriate sampling plot size was determined based on the canopy cover of the dominant species of the study area (1 m2). Then, in each unit, sampling was done along 3 transects of 100 m. Along each transect, 10 plots with dimensions of one square meter were placed at a distance of 10 m from each other. In each plot, the type, life forms, frequency of plant species, and species density were recorded. Species diversity indices were calculated using Ecological Methodology software. The values obtained from these indicators were analyzed in SPSS 24 statistical software and using the F test. The results of the Analysis of variance (ANOVA) showed that the highest values of the species diversity indices are in the middle altitudes (ecotone) class. ANOVA of the richness, evenness, and heterogeneity indices in different altitude classes showed that the values of the richness indices were not significant, but among the indices related to the heterogeneity, the Hill index and all the evenness indices were significant. Comparing the numerical indices of our communities enables us to determine the impact of environmental stress in a single community to choose the best habitat among a similar group for conservation. A community that has high diversity and richness is important for conservation. Therefore, the authorities must prevent the destruction of the vegetation of the study area in connection with the implementation of principled and correct management by the potential of the region, but also to reduce the pressure of livestock grazing and carry out corrective and restoration operations, to turn these rangelands towards rich diversity.

Gastrointestinal Bleeding in Congenital Bleeding Disorders.

Gastrointestinal bleeding (GIB) is serious, intractable, and potentially life-threatening condition. There is considerable heterogeneity in GIB phenotypes among congenital bleeding disorders (CBDs), making GIB difficult to manage. Although GIB is rarely encountered in CBDs, its severity in some patients makes the need for a comprehensive and precise assessment of underlying factors and management approaches imperative. Initial evaluation of GIB begins with assessment of hematological status; GIB should be ruled out in patients with chronic anemia, and in presentations that include hematemesis, hematochezia, or melena. High-risk patients with recurrent GIB require urgent interventions such as replacement therapy for treatment of coagulation factor deficiency (CFD). However, the best management strategy for CFD-related bleeding remains controversial. While several investigations have identified CBDs as potential risk factors for GIB, research has focused on assessing the risks for individual factor deficiencies and other CBDs. This review highlights recent findings on the prevalence, management strategies, and alternative therapies of GIB related to CFDs, and platelet disorders.

Risk and Management of Intracerebral Hemorrhage in Patients with Bleeding Disorders.

Intracerebral hemorrhage (ICH) is the most dreaded complication, and the main cause of death, in patients with congenital bleeding disorders. ICH can occur in all congenital bleeding disorders, ranging from mild, like some platelet function disorders, to severe disorders such as hemophilia A, which can cause catastrophic hemorrhage. While extremely rare in mild bleeding disorders, ICH is common in severe coagulation factor (F) XIII deficiency. ICH can be spontaneous or trauma-related. Spontaneous ICH occurs more often in adults, while trauma-related ICH is more prevalent in children. Risk factors that can affect the occurrence of ICH include the type of bleeding disorder and its severity, genotype and genetic polymorphisms, type of delivery, and sports and other activities. Patients with hemophilia A; afibrinogenemia; FXIII, FX, and FVII deficiencies; and type 3 von Willebrand disease are more susceptible than those with mild platelet function disorders, FV, FXI, combined FV-FVIII deficiencies, and type 1 von Willebrand disease. Generally, the more severe the disorder, the more likely the occurrence of ICH. Contact sports and activities can provoke ICH, while safe and noncontact sports present more benefit than danger. An important risk factor is stressful delivery, whether it is prolonged or by vacuum extraction. These should be avoided in patients with congenital bleeding disorders. Familiarity with all risk factors of ICH can help prevent occurrence of this diathesis and reduce related morbidity and mortality.

Curcumin: A therapeutic strategy for targeting the Helicobacter pylori-related diseases.

Helicobacter pylori is a significant human pathogen of the stomach's epithelial lining. This type of carcinogen is associated with gastric cancer, indigestion, peptic ulcers, and upper digestive diseases. Therefore, successful treatment and eradication of this bacterium are required to reduce the prevalence of these diseases, especially in high-risk individuals. Moreover, some concerns exist regarding the extensive use of elimination therapy, such as anti-microbial resistance and rising H. pylori-associated diseases. Since there is still no effective vaccine, finding alternative therapies would appear to be a worthwhile pursuit. In this regard, curcumin exhibits anti-inflammatory, anti-carcinogenic, anti-oxidant properties and is widely used as a natural product-derived medicine or nutraceutical. Furthermore, curcumin has been reported to have anti-bacterial activity. Therefore, curcumin might be an effective herbal-based medicine for preventing, managing, or treating H. pylori infection. This review discusses the anti-inflammatory, anti-cancer, and anti-bacterial properties of curcumin as it pertains to gastric cancer and H. pylori-associated diseases.

miR-483-3p suppresses the proliferation and progression of human triple negative breast cancer cells by targeting the HDAC8>oncogene.

Triple negative breast cancer (TNBC) is a heterogeneous subclass of breast cancer (BC) distinguished by lack of hormone receptor expression. It is highly aggressive and difficult to treat with traditional chemotherapeutic regimens. Targeted-therapy using microRNAs (miR) has recently been proposed to improve the treatment of TNBC in the early stages. Here, we explore the roles of miR-483-3p/HDAC8 HDAC8 premiR-vector on tumorigenicity in TNBC patients. Clinical TNBC specimens and three BC cell lines were prepared. miR-483-3p and expression levels were measured using quantitative real-time polymerase chain reaction. Cell cycle progression was assessed by a flow-cytometry method. We also investigated cell proliferation by 3-2, 5-diphenyl tetrazolium bromide assay and colony formation assay. We used a to overexpress miR-483-3p, and a HDAC8-KO-vector for knocking out the endogenous production of HDAC8. Our data showed significant downregulation of miR-483-3p expression in TNBC clinical and cell line samples. The HDAC8 was also upregulated in both tissue specimens and BC cell lines. We found that increased levels of endogenous miR-483-3p affects tumorigenecity of MDA-MB-231. Downregulation of HDAC8 using the KO-vector showed the same pattern. Our results revealed that the miR-483-3p suppresses cellular proliferation and progression in TNBC cell lines via targeting HDAC8. Overall, our outcomes demonstrated the role of miR-483-3p as a tumor suppressor in TNBC and showed the possible mechanism via HDAC8. In addition, targeted treatment of TNBC with miR-483-3p might be considered in the future.

Discovering the signature of a lupus-related microRNA profile in the Gene Expression Omnibus repository.

Lupus is one of the most prevalent systemic autoimmune diseases. It is a multifactorial disease in which genetic, epigenetic and environmental factors play significant roles. The pathogenesis of lupus is not yet well understood. However, deregulation of microRNAs (miRNAs) - one of the post-transcriptional regulators of genes - can contribute to the development of autoimmune diseases. Over the last two decades, advances in the profiling of miRNA using microarray have received much attention, and it has been demonstrated that miRNAs play a regulatory role in the pathogenesis of lupus. Therefore, dysregulated miRNAs can be considered as promising diagnostic biomarkers for lupus. This article is an overview of lupus-related miRNA profiling studies and arrays in the Gene Expression Omnibus (GEO) database. The aims of our study were to widen current knowledge of known dysregulated miRNAs as potential biomarkers of SLE and to introduce a bioinformatics approach to using microarray data and finding novel miRNA and gene candidates for further study. We identified hsa-miR-4709-5p, hsa-miR-140, hsa-miR-145, hsa-miR-659, hsa-miR-134, hsa-miR-150, hsa-miR-584, hsa-miR-409 and hsa-miR-152 as potential biomarkers by integrated bioinformatics analysis.

Sustainable closed-loop supply chain network for an integrated water supply and wastewater collection system under uncertainty.

Today, an increase in the drought and water shortage all around the world is a challengeable threat for different governments and international committees. Water supply chain aims to manage the water consumption and to control the water shortage. Contrary to most of previous studies focused on the forward directions of the water supply chain, this paper also considers the reverse logistics known as a Closed-Loop Supply Chain (CLSC). Hence, an integrated Water Supply and Wastewater Collection System (WSWCS) under uncertainty is proposed. Furthermore, regarding the trend of sustainable development, the environmental dimensions and social benefits of the integrated WSWCS are contributed. To meet the standards of the sustainable development in developing countries, a case study in Iran is applied to a novel multi-objective stochastic optimization model based on triple bottom lines of sustainability. Having already been employed to similar optimization problems, the Social Engineering Optimizer (SEO) has been never applied in this research area. Another innovation of this study is to introduce an improved multi-objective SEO to solve this complicated model. Eventually, with regards to an extensive comparison contributing to the Pareto-based metrics and different sensitivities, some managerial implications are concluded as the main findings.

A bi-objective home healthcare routing and scheduling problem considering patients' satisfaction in a fuzzy environment.

Home care services are an alternative answer to hospitalization, and play an important role in reducing the healthcare costs for governments and healthcare practitioners. To find a valid plan for these services, an optimization problem called the home healthcare routing and scheduling problem is motivated to perform the logistics of the home care services. Although most studies mainly focus on minimizing the total cost of logistics activities, no study, as far as we know, has treated the patients' satisfaction as an objective function under uncertainty. To make this problem more practical, this study proposes a bi-objective optimization methodology to model a multi-period and multi-depot home healthcare routing and scheduling problem in a fuzzy environment. With regards to a group of uncertain parameters such as the time of travel and services as well as patients' satisfaction, a fuzzy approach named as the Jimenez's method, is also utilized. To address the proposed home healthcare problem, new and well-established metaheuristics are obtained. Although the social engineering optimizer (SEO) has been applied to several optimization problems, it has not yet been applied in the healthcare routing and scheduling area. Another innovation is to develop a new modified multi-objective version of SEO by using an adaptive memory strategy, so-called AMSEO. Finally, a comprehensive discussion is provided by comparing the algorithms based on multi-objective metrics and sensitivity analyses. The practicality and efficiency of the AMSEO in this context lends weight to the development and application of the approach more broadly.

A Comprehensive Overview of Coagulation Factor V and Congenital Factor V Deficiency.

Coagulation factor (F) V is a glycoprotein that plays an essential role in the formation of the prothrombinase complex, which is critical for progressing clot formation. FV deficiency is a rare bleeding disorder with an estimated incidence of one per 1 million in the general population. The disorder is manifested with a wide array of clinical bleeding events. The most common bleeding features of FV deficiency are mucosal bleedings. Life-threatening manifestations are rarely seen in this disorder. FV deficiency is diagnosed using routine coagulation tests and FV activity assay. A wide spectrum of mutations including missense, nonsense, and frameshift is observed throughout the F5 gene. Although fresh frozen plasma is the dominant therapeutic choice, a newly introduced plasma-derived FV concentrate was found effective in in vitro correction of prothrombin time, activated partial thromboplastin time, and thrombin generation parameters in severe FV deficiency and should provide more targeted treatment for patients with FV deficiency in the future.

A hybrid hierarchical soft computing approach for the technology selection problem in brick industry considering environmental competencies: A case study.

Brick manufacturing is an important industry which produces some fundamental building materials. Since brick production industries have environmental adverse effects such as air pollution, excessive energy consumption as well as waste production, they have become more challenging to manage as they face increasing pressure to improve economic performance and the green and clean production concerns. Concerning these issues and taking into account the current state of the literature in this area, this paper, proposes a hybrid hierarchical fuzzy multiple-criteria group decision making (HH-FMCGDM) model based on a modified fuzzy analytic hierarchy process (MFAHP) to evaluate and rank the related alternative technologies based on various criteria including economic, environmental, market related, technical advantages, and so on. In the proposed method MFAHP is utilized to determine the weights of the criteria. Also, a new method is presented to assign a weight factor for each decision maker (DM) in the group decision-making process. Also, we propose a fuzzy extended version of TOPSIS method as an evaluation tool to calculate the local priority of candidates of brick manufacturing technologies. Afterward, in order to avoid the data loss of DMs' judgments, the final rank of alternatives are obtained based on the proposed last aggregation approach. To illustrate the efficiency of the proposed approach, a real-life case study in a brick industry is done based on our approach. Then, a sensitivity analysis is done to assess the robustness and sensitiveness of the obtained results from the proposed approach. Finally, some managerial insights are suggested to increase the applicability of the proposed HH-FMCGDM approach for real cases.

Using artificial neural network in determining postharvest LIFE of kiwifruit.

BACKGROUND: Artificial intelligence systems have been employed for the development of predictive models that estimate many agricultural processes. RESULTS: In present study, the predictive capabilities of artificial neural networks (ANNs) were evaluated with respect to assessing fruit firmness as a postharvest life index, with determinations made at four stages of storage: 1, 60, 120 and 180 days after harvesting. Single concentrations of nitrogen (N), potassium (K), calcium (Ca) and magnesium (Mg) on fruit (D1 ), all of these nutrient concentrations (D2 ), the ratios of the nutrient concentrations alone (D3 ), and a combination of nutrient concentrations and their ratios (D4 ), were considered. CONCLUSION: The results obtained showed that fruit firmness at 1 and 60 days after harvesting was not influenced by nutrients. However, the ANN model estimated fruit firmness of 120 and 180 days, respectively, for D1 and D3 more accurately than for the D2 and D4 datasets. Application of D3 (nitrogen/calcium ratio) as the input dataset improved predictions of fruit firmness, with a correlation coefficient of 0.85 between the measured and estimated data. © 2019 Society of Chemical Industry.

Matrix metalloproteinase-2 C-735T and its interaction with matrix metalloproteinase-7 A-181G polymorphism are associated with the risk of preeclampsia: influence on total antioxidant capacity and blood pressure.

Matrix metalloproteinase (MMP) -2 C-735 T and MMP-7 A-181 G genotypes were studied in 144 pregnant patients with mild and severe preeclampsia and 103 healthy pregnant women. Significantly higher frequencies of CT and TT genotypes in patients compared to controls increased the risk of preeclampsia by 2.42 and 3.13 times, respectively. In severe preeclamptic women in the presence of MMP-2 CT the level of total antioxidant capacity was significantly lower than MMP-2 CC genotype. Also, in the presence of MMP-2 CT + TT blood pressure was significantly increased compared to CC genotype in all the patients. The combined presence of MMP-2 T and the MMP-7 A alleles compared to MMP-2 C and MMP-7 A alleles significantly increased the risk of preeclampsia by 3.08-fold. Our findings demonstrate an association between the MMP-2 C-735 T polymorphism with blood pressure and the risk of preeclampsia. Also, in the presence of polymorphism total antioxidant capacity level decreased in severe preeclampsia. Impact statement What is already known on this subject: Matrix metalloproteinases (MMPs) including MMP-2 might be involved in the pathogenesis of preeclampsia through alteration of invasive ability of trophoblastic cells and abnormal placentation. In one available study the absence of association between MMP-2 C-735T polymorphism with gestational hypertension or preeclampsia has been reported. What the results of this study add: We found that the presence of MMP-2 C-735T polymorphism increased the risk of preeclampsia and there was a significantly lower level of total antioxidant capacity in the presence of the polymorphism in severe preeclampsia. Also, we found significantly higher systolic and diastolic blood pressures in the presence of MMP-2 C-735T polymorphism. We detected a synergism between the MMP-2 T and the MMP-7 A alleles that increased the risk of preeclampsia. What the implications are of these findings for clinical practice and/or further research: New findings of our study are involvement of lower activity MMP-2 -735 T allele and its synergism with MMP-7 A allele, low promoter activity allele, in the pathogenesis of preeclampsia through possible impairment of placentation and also by decreased total antioxidant capacity and increased blood pressure. Further association studies of the role of MMP-2 polymorphism and MMP-2 activity in relation to oxidative stress parameters and blood pressure could elucidate the role of MMP-2 and MMP-7 in the pathogenesis of preeclampsia.

An optimised mouse model of chronic pancreatitis with a combination of ethanol and cerulein.

INTRODUCTION: Chronic pancreatitis (CP) is an intractable and multi-factorial disorder. Developing appropriate animal models is an essential step in pancreatitis research, and the best ones are those which mimic the human disorder both aetiologically and pathophysiologically. The current study presents an optimised protocol for creating a murine model of CP, which mimics the initial steps of chronic pancreatitis in alcohol chronic pancreatitis and compares it with two other mouse models treated with cerulein or ethanol alone. MATERIAL AND METHODS: Thirty-two male C57BL/6 mice were randomly selected, divided into four groups, and treated intraperitoneally with saline (10 ml/kg, control group), ethanol (3 g/kg; 30% v/v), cerulein (50 µg/kg), or ethanol + cerulein, for six weeks. Histopathological and immunohistochemical assays for chronic pancreatitis index along with real-time PCR assessments for mRNA levels of inflammatory cytokines and fibrogenic markers were conducted to verify the CP induction. RESULTS: The results indicated that CP index (CPI) was significantly increased in ethanol-cerulein mice compared to the saline, ethanol, and cerulein groups (p < 0.001). Interleukin 1ß (IL-1ß), tumor necrosis factor α (TNF-α), transforming growth factor ß (TGF-ß), α-smooth muscle actin (α-SMA), and myeloperoxidase activity were also significantly greater in both cerulein and ethanol-cerulein groups than in the saline treated animals (p < 0.001). Immunohistochemical analysis revealed enhanced expression of TGF-ß and α-SMA in ethanol-cerulein mice compared to the saline group. CONCLUSIONS: Intraperitoneal (IP) injections of ethanol and cerulein could successfully induce CP in mice. IP injections of ethanol provide higher reproducibility compared to ethanol feeding. The model is simple, non-invasive, reproducible, and time-saving. Since the protocol mimics the initial phases of CP development in alcoholics, it can be used for investigating basic mechanisms and testing new therapies.

Diagnostic value of CD117 in differential diagnosis of acute leukemias.

C-kit receptor (CD117) and its ligand, stem cell factor, play a key role in normal hematopoiesis. It has been demonstrated that its expression extremely increases in leukemias with myeloid commitment. We analyzed findings on CD117 expression together with other myeloid related markers in 203 de novo acute leukemias, referred to Iranian immunophenotyping centers: Iranian Blood Transfusion Organization (IBTO) and Baghiatallah Hospital (BH). All cases were characterized based on the French American British cooperative group (FAB) and European Group for Immunological Classification of Leukemias (EGIL). The cases comprised of 111 acute myeloblastic leukemia (AML), 86 acute lymphoblastic leukemia (ALL), and 6 acute undifferentiated leukemia (AUL). CD117 was positive in 75 % of AML and 50 % of AUL, whereas none of the ALL cases was positive for this marker. Although CD117 was positive in 100 % of M5a cases, no M5b positive was found (p = 0.036). The calculated specificity for myeloid involvement was 100 % for CD117 and CD33, and 98 % for CD13 and CD15 (p < 0.001). The calculated sensitivity for myeloid involvement was 83, 76, 64, and 41 % for CD13, CD117, CD33, and CD15, respectively (p < 0.001). We concluded that CD117 expression is a specific and rather sensitive marker for differential diagnosis between AML and ALL, and except for M5 subtypes, it fails to determine FAB subtypes; lack of expression in M5 can identify M5b. Therefore, it should be included in the routine primary panel for diagnosis of acute leukemias.

Synbiotic yogurt-ice cream produced via incorporation of microencapsulated lactobacillus acidophilus (la-5) and fructooligosaccharide.

Yogurt-ice cream is a nutritious product with a refreshing taste and durability profoundly longer than that of yogurt. The probiotic Lactobacillus acidophilus (La-5) cells either in free or encapsulated form were incorporated into yog-ice cream and their survivability were studied. Fructooligosaccharide (FOS) as a prebiotic compound at three levels (0, 4 & 8 % w/w) was added to yogurt-ice cream mix and its effects on some chemical properties, overrun and firmness of product were evaluated. The higher the incorporated FOS concentration, the lower were the pH value and higher the total solid content of treatments. FOS incorporation (8 %) significantly increased the overrun of treatments and reduced their firmness. The viable counts of free probiotics decreased from ~9.55 to ~7.3 log cfu/g after 60 days of frozen storage while that of encapsulated cells merely decreased less than 1 log cycle. Encapsulation with alginate microbeads protected the probiotic cells against injuries in the freezing stage as well as, during frozen storage.

Effects of lupeol and flutamide on experimentally-induced polycystic ovary syndrome in mice.

Objectives: Polycystic ovary syndrome (PCOS) is one of the main causes of infertility in women. This study was conducted to uncover the effects of lupeol as an anti-androgenic triterpene on experimentally-induced PCOS in mice. Materials and Methods: Eighty immature female mice were divided into 4 groups: Control (C), PCOS (P), Lupeol (L), and Flutamide (F). PCOS was induced in test groups by injection of Dehydroepiandrosterone (60 mg/kg/day, IP) for twenty days. Following the PCOS induction, the two groups of L and F were treated with lupeol (40 mg/kg/day) and/or flutamide (10 mg/kg/day) respectively and the two groups of C and P received sesame oil (0.1 ml/mouse/day) for 15 days. After the treatment period, ten animals in each group were selected for collecting blood and ovary samples. In vitro fertilization assessment was carried out on 10 remaining mice in each group. The hormonal assays and oxidative stress biomarker determination were performed on serum and tissue samples. Moreover, histopathological analyses were conducted on the ovaries. Results: PCOS-elevated concentration of LH and Testosterone was significantly (P<0.05) lowered in lupeol and flutamide-received animals. Lupeol and flutamide both reduced PCOS-induced fibrosis and the number of atretic follicles. Both compounds declined the PCOS-increased lipid peroxidation and protein oxidation in serum and the ovaries. Lupeol increased the PCOS-reduced fertility rate and decreased the number of arrested embryos by 12%. Conclusion: These findings indicate that lupeol could be a novel compound in the treatment of PCOS as it reduced PCOS-induced structural and also functional disorders.

Anti-inflammatory effects of Mentha pulegium L. extract on human peripheral blood mononuclear cells are mediated by TLR-4 and NF-κB suppression.

There is great interest in evaluating the anti-inflammatory properties of new herbal products. Thus, the effects of Mentha pulegium L. extract on gene and protein expressions of pro-inflammatory mediators and transcription factors were determined. The hydro-ethanolic extract of Mentha pulegium L. was obtained and optimal non-cytotoxic concentrations of the extract were determined by MTT assay. Then, three different concentrations of Mentha pulegium L. (10, 30, and 90 µg/mL) were used to pre-treat the lipopolysaccharide (LPS)-stimulated and non-stimulated peripheral blood mononuclear cells (PBMCs) of 10 healthy individuals. Finally, the tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß), IL-6, Toll-like receptor-4 (TLR-4), nuclear factor-kappa B (NF-κB) p65, activator protein-1 (AP-1), inducible nitric oxide synthase (iNOS), and cyclooxygenase-2 (COX-2) gene expressions and TNF-α, IL-1ß, IL-6, TLR-4, prostaglandin E2 (PGE2), and COX-2 protein levels were measured. MTT results showed that there is no significant difference in cell viability among 10, 20, 40, and 80 µg/mL concentrations of Mentha pulegium L. extract at 24, 48, and 72 h (P > 0.05). The IC50 values were 236.1, 147.0, and 118.0 µg/mL after 24, 48, and 72 h respectively. TNF-α, IL-1ß, IL-6, TLR-4, iNOS, and NF-κB p65 mRNA levels in the pre-treated LPS-stimulated PBMCs were concentration-dependently reduced (P < 0.01 for TNF-α, TLR-4, and NF-κB p65; P < 0.05 for IL-1ß, IL-6, and iNOS). Also, the protein levels of pro-inflammatory mediators decreased and these differences were significant for TNF-α, IL-1ß, and TLR-4 (P < 0.001, P < 0.01, and P < 0.001, respectively). Mentha pulegium L. extract decreased the expression and biosynthesis of pro-inflammatory mediators. These effects are mainly mediated by TLR-4 and NF-κB suppression. Thus, Mentha pulegium L. could be useful in treating or ameliorating chronic inflammatory diseases.

Natural Anticoagulant Protein Levels in Patients With Beta-Thalassemia Major: A Case-Control Study.

Background: ß-thalassemia is a group of inherited blood disorders that affect the production of ß-globin chains, leading to the reduction or absence of these chains. One of the complications observed in patients with ß-thalassemia major (ß-TM) is thrombosis, especially in those who receive frequent blood transfusions. This may be due to a decrease in the levels of the natural anticoagulants: protein C (PC), total protein S (PS), and antithrombin (AT). Methods: In this case-control study, patients with ß-TM, who had received at least 20 packed cell transfusions during their lifetime, were included. Patients with other underlying diseases like bleeding or thrombotic disorders were excluded. Totally, 118 patients with ß-TM and 120 healthy individuals were included. Results: The mean level of PC and AT was significantly lower in patients with ß-TM (48.2 ± 65.4 and 57.42 ± 13.6, respectively) compared to the control group (97.1 ± 21.46 and 81.79 ± 14.3, respectively), with P value of 0.001 and 0.01, respectively. Although the difference was not statistically significant (P = 0.1), a similar trend was observed for total PS (61.12 ± 21.12 for patients versus 72.2 ± 35.2 for the control group). Of note, the decrease in PC, AT, and total PS levels compared to the control group was 50.36%, 27.5%, and 15.34%, respectively. Conclusions: It seems that ß-TM patients who receive prolonged blood transfusions frequently are at an increased risk of decreased in natural anticoagulants levels and therefore potentially are at risk of thrombosis.