Improvement of Drought Tolerance by Exogenous Spermidine in Germinating Wheat (Triticum aestivum L.) Plants Is Accompanied with Changes in Metabolite Composition.

Drought is one of the most important environmental factors reducing the yield and production of crops, including wheat. Polyamines are closely associated with plant stress tolerance. The present study investigated the mechanisms through seed germination with spermidine protecting wheat varieties from drought stress. In the first experiment, the effects of spermidine on the germination of wheat varieties, namely Rakhshan, Mihan, Sirvan and Pishgam, were investigated in three drought levels, namely 0, -2, and -4 MPa induced by polyethylene glycol 6000. Analysis of variance indicated that spermidine, drought stress and interaction between varieties and drought stress were significant for all traits, and with severity of stress, all traits significantly decreased. In the second experiment, detailed gene expression and non-targeted metabolomics analyses were carried out using the Rakhshan and Mihan varieties after germination, with or without spermidine treatment and/or drought stress. According to the biomass parameters, the Mihan variety showed relatively better growth compared to the other variety, but the Rakhshan one showed more pronounced responses at gene expression level to exogenous spermidine than the Mihan variety. Overall, these results showed that spermidine increased the drought tolerance of wheat at the germination stage, due to specific role of polyamine metabolism in the development of effective responses under drought stress.

Light Spectral Composition Modifies Polyamine Metabolism in Young Wheat Plants.

Although light-emitting diode (LED) technology has extended the research on targeted photomorphogenic, physiological, and biochemical responses in plants, there is not enough direct information about how light affects polyamine metabolism. In this study, the effect of three spectral compositions (referred to by their most typical characteristic: blue, red, and the combination of blue and red [pink] lights) on polyamine metabolism was compared to those obtained under white light conditions at the same light intensity. Although light quality induced pronounced differences in plant morphology, pigment contents, and the expression of polyamine metabolism-related genes, endogenous polyamine levels did not differ substantially. When exogenous polyamines were applied, their roborative effect were detected under all light conditions, but these beneficial changes were correlated with an increase in polyamine content and polyamine metabolism-related gene expression only under blue light. The effect of the polyamines on leaf gene expression under red light was the opposite, with a decreasing tendency. Results suggest that light quality may optimize plant growth through the adjustment of polyamine metabolism at the gene expression level. Polyamine treatments induced different strategies in fine-tuning of polyamine metabolism, which were induced for optimal plant growth and development under different spectral compositions.

Novel Metal-Organic Framework Nanoparticle for Letrozole Delivery: A New Advancement in Breast Cancer Treatment.

Water-stable metal-organic frameworks based on UIO-66@NH2 were synthesized to transport Letrozole into breast cancer cells. The UIO-66@NH2 nanoparticles had a spherical shape and triangular base pyramid morphology, with a size range of 100-200 nm. Fourier transform infrared spectroscopy confirmed the efficient adsorption of Letrozole on UIO-66@NH2. The drug release profile showed a gradual, pH-dependent release of Letrozole from the nanoparticles, with a significant increase in acidic environments, indicating the adaptable release potential of UIO-66@NH2@Let in the breast cancer microenvironment. The size and entrapment efficiency were more stable at 4 °C than at 25 °C. To evaluate the cytotoxic effects of UIO-66@NH2@Let, MTT assay, gene expression analysis, flow cytometry, reactive oxygen species generation, migration assay, and DAPI staining were performed. Moreover, according to IC50 results, the incorporation of Letrozole into UIO-66@NH2 significantly improved its anticancer activity. The results also showed that the developed formulations induced apoptosis through both intrinsic and extrinsic pathways and inhibited cancer progression. The efficacy of the formulations in inducing apoptosis was validated by DAPI staining microscopy and flow cytometry analysis. Therefore, the Letrozole-loaded UIO-66@NH2 MOFs developed in this study can be considered as a unique and sophisticated anticancer delivery nanosystem with promising in vitro anticancer properties.

Tumor Organoid as a Drug Screening Platform for Cancer Research.

A number of studies have been conducted on the application of 3D models for drug discovery, drug sensitivity assessment, and drug toxicity. Most of these studies focused on disease modelling and attempted to control cellular differentiation, heterogeneity, and key physiological features to mimic organ reconstitution so that researchers could achieve an accurate response in drug evaluation. Recently, organoids have been used by various scientists due to their highly organotypic structure, which facilitates the translation from basic research to the clinic, especially in cancer research. With this tool, researchers can perform high-throughput analyses of compounds and determine the exact effect on patients based on their genetic variations, as well as develop personalized and combination therapies. Although there is a lack of standardization in organoid culture, patientderived organoids (PDO) have become widely established and used for drug testing. In this review, we have discussed recent advances in the application of organoids and tumoroids not only in cancer research for drug screening but also in clinical trials to demonstrate the potential of organoids in translational medicine.

The ß2-adrenergic receptor agonist terbutaline upregulates T helper-17 cells in a protein kinase A-dependent manner.

BACKGROUND: T helper 17 (Th17) cells produce IL-17A cytokine and can exacerbate autoimmune diseases and asthma. The ß2 adrenergic receptor is a g protein-coupled receptor that induces cAMP second messenger pathways. We tested the hypothesis that terbutaline, a ß2-adrenergic receptor-specific agonist, promotes IL-17 secretion by memory Th17 cells in a cAMP and PKA-dependent manner. METHODS: Venous peripheral blood mononuclear cells (PBMC) from healthy human participants were activated with anti-CD3 and anti-CD28 antibodies. Secreted IL-17A was measured by enzyme linked immunosorbent assay, intracellular IL-17A, and RORγ were measured using flow cytometry, and RORC by qPCR. Memory CD3+CD4+CD45RA-CD45RO+ T cells were obtained by immunomagnetic negative selection and activated with tri-antibody complex CD3/CD28/CD2. Secreted IL-17A, intracellular IL-17A, RORC were measured, and phosphorylated-serine133-CREB was measured by western blotting memory Th cells. RESULTS: Terbutaline increased IL-17A (p < 0.001), IL-17A+ cells (p < 0.05), and RORC in activated PBMC and memory Th cells. The PKA inhibitors H89 (p < 0.001) and Rp-cAMP (p < 0.01) abrogated the effects of terbutaline on IL-17A secretion in PBMC and memory T cells. Rolipram increased IL-17A (p < 0.01) to a similar extent as terbutaline. P-Ser133-CREB was increased by terbutaline (p < 0.05) in memory T cells. CONCLUSION: Terbutaline augments memory Th17 cells in lymphocytes from healthy participants. This could exacerbate autoimmune diseases or asthma, in cases where Th17 cells are considered to be pro-inflammatory.

A high-sensitivity electrochemical immunosensor based on mobile crystalline material-41-polyvinyl alcohol nanocomposite and colloidal gold nanoparticles.

A novel competitive immunosensor was developed as a model system using anti-human serum albumin (HSA)-conjugated gold nanoparticles (AuNPs) as an electrochemical label and mobile crystalline material-41 (MCM-41)-polyvinyl alcohol (PVA) mesoporous nanocomposite as an immobilization platform. However, no attempt has yet been made to use the MCM-41 as the supporting electrolyte for the electrosynthesis of nonconducting polymer nanocomposite. This hybrid membrane was evaluated extensively by using field emission scanning electron microscopy (FESEM), cyclic voltammetry (CV), and differential pulse voltammetry (DPV) to determine its physicochemical and electrochemical properties in immunosensor application. FESEM revealed an appropriate and stable attachment between HSA and MCM-41 and also a dense layer deposition of MCM-41-HSA-PVA film onto the electrode surfaces. DPV was developed for quantitative determination of antigen in biological samples. A decrease in DPV responses was observed with increasing concentrations of HSA in standard and real samples. In optimal conditions, this immunosensor based on MCM-41-PVA nanocomposite film could detect HSA in a high linear range (0.5-200 µg ml⁻¹) with a low detection limit of 1 ng ml⁻¹. The proposed method showed acceptable reproducibility, stability, and reliability and could also be applied to detect the other antigens.

Quantitative Analysis of Food Safety Policy-Based on Text Mining Methods.

Recently, food safety and cold chain food have been closely related to the epidemic. The party and the state have intensified efforts to solve food safety problems and prevent possible epidemic risks. China has issued a series of policies and plans to strengthen food safety supervision to improve the food safety policy system. To our knowledge, little work has studied policy problems of food safety with in-depth quantitative analysis for an extended period. In accordance with the different national policies and regulations for food safety, this paper fills the gap by analyzing the policies and comparing the central and local policies issued in China from 2007-2022. In addition, the Latent Dirichlet Allocation (LDA) topic model and K-Means clustering model are constructed to analyze the content of food safety policies and identify hot topics. Finally, a quantitative analysis of China's food safety policies is made from four aspects: the number of policy release years, the distribution area, the range of action, and the affiliated institutions. The results show that: (a) there is a partial surge in food safety policies issued in 2007, 2011, and 2017; (b) the local food safety policy has a high inheritance to the central policy content, and the trends of annual publication number are highly consistent; (c) the innovation of different policy contents in the region have their own characteristics; (d) the proportion of compulsory and capacity policies is much more significant than that of other types of policies. This paper provides some novel insights into food safety policies.

Geographical distribution and molecular epidemiology of cutaneous leishmaniasis in Fars Province, southern Iran.

Cutaneous leishmaniasis (CL) is one of the important zoonotic diseases in Iran, particularly in Fars Province, southern Iran. The purpose of this descriptive cross-sectional study was to investigate the molecular identification and geographical distribution of anthroponotic and zoonotic CL in southern Iran, during 2018-2019. Overall, 161 patients with CL referred to the Leishmaniasis Diagnostic Laboratory, Valfajr Health Center, Shiraz, Iran, were included in this study. The smears were prepared from the lesion borders of patients and stained with Giemsa and diagnosed microscopically. For molecular identification, the genomic DNA of each sample was extracted, and PCR method was used. The geographical distribution map was prepared using ArcMap software. Finally, the possible correlation between the frequencies of CL in various subgroups was statistically analyzed by Chi-square test, using SPSS software. Of 161 positive samples confirmed by both microscopy and PCR, 126 (78.3%) and 35 (21.7%) samples were shown to be L. major and L. tropica, respectively. Also, 87 (54%) patients were male, and 74 (46%) were female. The study showed that anthroponotic cutaneous leishmaniasis (ACL) was detected only in Shiraz city, while zoonotic cutaneous leishmaniasis (ZCL) was observed both in Shiraz and most counties of Fars Province. Furthermore, the most CL infections occurred in district 8 among the different districts of Shiraz municipality, which requires serious attention.

The protective effect of L-carnitine on testosterone synthesis pathway, and spermatogenesis in monosodium glutamate-induced rats.

BACKGROUND: Monosodium glutamate (MSG) is a food ingredient that is increasingly used commercially. MSG leads to oxidative stress, consequently suppressing steroid hormone production that causes defects in male reproductive system. This study aimed to evaluate the effect of L-carnitine as an antioxidant on testicular damage in MSG-induced male rats. METHODS: Sixty adult male Spargue-Dawley rats were randomly divided into six groups of ten as follows: control (water), sham (normal saline), L-carnitine (200 mg/kg b.w), MSG (3 g/kg b.w), MSG + L-carnitine 100 (3 g/kg b.w of MSG and 100 mg/kg b.w of L-carnitine), and MSG + L-carnitine 200 (3 g/kg b.w of MSG and 200 mg/kg b.w of L-carnitine). The treatment was administered by oral gavage for six months. Serum levels of Malondialdehyde (MDA), Total Anti-oxidant Capacity (TAC), LH, FSH, testosterone, and mRNA expressions of Star, Cyp11a1, and Hsd17b3 genes, and histological and stereological changes were assessed. RESULTS: L-carnitine led to a significant decrease in the level of MDA and a significant rise in the serum levels of TAC, LH, FSH, and mRNA expression of Star and Cyp11a1 compared to the MSG group (p < 0.05). Furthermore, stereological results indicated a significant increment in the number of sexual lineage cells, the total volume of the testis, length, diameter, and volume of seminiferous tubules, the height of the germinal epithelium, sperm count, and sperm motility (p < 0.05) in MSG + L-carnitine 200 compare to MSG group. CONCLUSION: The study's findings demonstrated that L-carnitine due to its anti-oxidant properties, ameliorated the reproductive abnormalities in the male rats exposed to MSG.

Evaluation of morphological traits of wheat varieties at germination stage under salinity stress.

Salinity stress is one of the major plant growth-limiting factors in agriculture. It causes ionic imbalance, thus decrease the growth and yield attributes of crops especially wheat. Seedling stage is considered as one of the most sensitive stages under salinity stress. Survival of seeds at seedling stage can overcome the adverse impacts of salinity stress to some extent. Selection of salt tolerant varieties in seedling stage is considered as an effective strategy. Hence, current study was conducted to examine the seed germination responses of four wheat varieties under different levels of salinity. The wheat varieties such as 'Rakhshan', 'Sirvan', 'Pishgam' and 'Heidari' were grown and four salinity levels of 0, 4, 8 and 12 dS/m were applied under completely randomized design. The varieties such as 'Sirvan', 'Rakhshan' and 'Heidari' showed significant response for germination compared to 'Pishgam' at 12 dS/m salinity. Furthermore, the variety 'Rakhshan' showed significantly higher germination rate (20.3%), higher root length (33.4%) and higher shoot length (84.3%) than 'Pishgam', 'Sirvan' and 'Sirvan' respectively. However, contrasting results were obtained for dry weight of seedlings where 12.2% increase was observed in 'Pishgam' over 'Rakhshan' at 12 dS/m salinity that might be due to higher capability to uptake of Na and Cl ions. In conclusion, 'Rakhshan' wheat variety proved to be the most salinity tolerant as it grew better under saline soil conditions. More investigations at field level are recommended to declare 'Rakhshan' as salinity tolerant cultivar.

Genome-wide analysis of the polyamine oxidase gene family in wheat (Triticum aestivum L.) reveals involvement in temperature stress response.

Amine oxidases (AOs) including copper containing amine oxidases (CuAOs) and FAD-dependent polyamine oxidases (PAOs) are associated with polyamine catabolism in the peroxisome, apoplast and cytoplasm and play an essential role in growth and developmental processes and response to biotic and abiotic stresses. Here, we identified PAO genes in common wheat (Triticum aestivum), T. urartu and Aegilops tauschii and reported the genome organization, evolutionary features and expression profiles of the wheat PAO genes (TaPAO). Expression analysis using publicly available RNASeq data showed that TaPAO genes are expressed redundantly in various tissues and developmental stages. A large percentage of TaPAOs respond significantly to abiotic stresses, especially temperature (i.e. heat and cold stress). Some TaPAOs were also involved in response to other stresses such as powdery mildew, stripe rust and Fusarium infection. Overall, TaPAOs may have various functions in stress tolerances responses, and play vital roles in different tissues and developmental stages. Our results provided a reference for further functional investigation of TaPAO proteins.

Molecular identification and subtypes distribution of Blastocystis sp. isolated from children and adolescent with cancer in Iran: evaluation of possible risk factors and clinical features.

PURPOSE: This study aimed to determine the molecular characterization and subtype distribution of Blastocystis sp. isolated from cancer children and adolescents in Shiraz, Fars province, southwestern Iran. METHODS: Overall, 200 fecal samples obtained from cancer children and adolescents under 18 years old (107 males and 93 females) and checked by microscopy, culture, and molecular methods (PCR). Possible etiological factors and clinical characteristics of Blastocystis infection were also evaluated and compared between Blastocystis infected and non-infected patients. RESULTS: Thirteen of 200 (6.5%) stool samples were positive for Blastocystis by microscopy. While 21 of 200 (10.5%) were positive by culture, and 24 of 200 (12%) were positive by PCR. Out of 24 positive samples tested by PCR and sequencing, ST3 was reported as the most common subtype (nine samples, 37.5%), followed by ST2 (eight samples, 33.3%), ST1 (five samples, 20.9%), and ST7 (two samples, 8.3%). The prevalence of Blastocystis infection in males was significantly higher than females (p = 0.024). Also, Blastocystis was more prevalent in patients who had received at least eight chemotherapy cycles than fewer (p = 0.002). However, no associations were found between Blastocystis-positive rate and age, residence, type of cancers, or contact with animals. Also, there was no significant difference between frequency of Blastocystis subtypes in symptomatic and asymptomatic cancer patients. CONCLUSIONS: Various controlled epidemiologic and topographic studies need to confirm or reject these possible associations with Blastocystis infection. The data from this study are an invaluable addition to the growing body of research studies on Blastocystis infection in cancer patients.

Stevia rebaudiana extract attenuate metabolic disorders in diabetic rats via modulation of glucose transport and antioxidant signaling pathways and aquaporin-2 expression in two extrahepatic tissues.

Today, plant-based therapies have been attracted attention to overcome diabetes complications. This study was an attempt to evaluate whether antidiabetic and nephroprotective effects of Stevia Rebaudiana Bertoni (SRB) can be exerted via upregulation of GLUT-4, SNAP23, and Stx4 in skeletal muscles or modulation of AQP2 mRNA expression and antioxidant signaling pathway activity (Nrf2/Keap1) in kidneys. To achieve this aim, diabetes was induced via STZ-nicotinamide (STZ-NA). Diabetes increased the level of Blood Urea Nitrogen (BUN), serum creatinine, Fasting Blood Sugar (FBS), and Keap1 mRNA expression, which was coincide with reduction in mRNA levels of Nrf2, GLUT4, SNAP23, and Stx4. SRB and metformin compensate mentioned variables. However, SRB extract was more effective than metformin to increase the levels of GLUT4 and Nrf2 mRNA. It seems that SRB might attenuate the diabetic complications via manipulating the glucose uptake components in peripheral tissues and might exert the nephroprotective effects by modulation of AQP2, and Nrf2/Keap1 mRNA expression. PRACTICAL APPLICATIONS: Synthetic antidiabetic drugs have been only partially successful in controlling the diabetic complications. Moreover, use of these drugs is associated with a number of adverse effects. Over the past few years, a renewed attention has been paid to the prevention and treatment of diabetes using medicinal plants and functional foods. SRB that have been known as natural sweetener for centuries, is a such natural agent that has high source of various phytochemicals with antidiabetic, renal protective, antitumor, and antioxidant properties. In the current study, possible molecular mechanisms of insulin-mimetic and nephroprotective effects of SRB extract was evaluated in diabetic rats. Due to powerful antihyperglycemic and nephroprotective effects of SRB extract that were showed in this study and previous studies, hence the fact that SRB is to be highlighted for future research as a new therapeutic agent for diabetes.

The protective effect of Stevia rebaudiana Bertoni on serum hormone levels, key steroidogenesis enzymes, and testicular damage in testes of diabetic rats.

Diabetes Mellitus (DM) is a kind of metabolic endocrine diseases, which has various effects on the gonadal system. The current study aimed to examine the effect of Stevia rebaudiana Bertoni extract on the mRNA expression involved in testosterone synthesis, and stereological parameters in rat testes, for improving diabetes complications. In this study, 48 rats were randomly classified into control, diabetic (streptozocin 60 mg/kg + nicotinamide 120 mg/kg), diabetic + Stevia (400 mg/kg), and diabetic + metformin (500 mg/kg) groups. Finally, Fasting Blood Sugar (FBS) level, the serum level of LH and testosterone, the Star, Cyp11a1, and Hsd17b3 gene expressions, and changes in the testis histology were evaluated. The results indicated a decrease in body weight, serum LH and testosterone level, the star gene expression, stereological changes of testes, and an increase in the FBS level in diabetic group, compared with the control group (P<0.05). Nonetheless, Stevia significantly reduced the FBS and increased the serum LH level, in comparison with diabetic rats (P<0.05), but no significant differences in the serum testosterone level and the Star gene expression has been found. Stevia also resulted in an increase in weight, testis volume, the number of sexual lineage cells, and sperm count and motility, compared to diabetic rats (P<0.05). Due to its antioxidant properties, Stevia enhanced the alteration in spermatogenesis and stereological characteristics in diabetic rat testes. Hence, Stevia could diminish the reproductive system problems and improve infertility in diabetic male rats.

Assessment of Cannabinoids Agonist and Antagonist in Invasion Potential of K562 Cancer Cells

Background: The prominent hallmark of malignancies is the metastatic spread of cancer cells. Recent studies have reported that the nature of invasive cells could be changed after this phenomenon, causing chemotherapy resistance. It has been demonstrated that the up-regulated expression of matrix metalloproteinase (MMP) 2/MMP-9, as a metastasis biomarker, can fortify the metastatic potential of leukemia. Furthermore, investigations have confirmed the inhibitory effect of cannabinoid and endocannabinoid on the proliferation of cancer cells in vitro and in vivo. Methods: In the present study, the inhibitory effect of WIN 55212-2 (a CB1/CB2 receptor agonist) and AM251 (a selective CB1 receptor antagonist) on K562 cells, as a chronic myelogenous leukemia (CML) model, was evaluated using MTT and invasion assay. Expressions of MMP-2 and MMP-9 were then assessed by Western blot analysis. Results: The data obtained from MTT assay showed that WIN 55212-2 could attenuate cell proliferation; however, AM251 was less effective in this regard. Our results showed that WIN 55212-2 considerably reduced cancer cell invasiveness, while AM251 exhibited a converse effect. Moreover, CB1 activation resulted in decreased expression of MMP-2 and MMP-9. Conclusion: Our findings clarifies that CB1 receptors are responsible for anti-invasive effects in the K562 cell line.

Cutaneous leishmaniasis associated with Systemic Lupus Erythematosus (SLE).

Cutaneous Leishmaniasis (CL) is a protozoan disease caused by Leishmania spp. and is endemic in the Americas, the Mediterranean basin, Middle East, and Central Asia. There are reports regarding the co-infection of CL with other diseases, especially immune system disorders. Herein, we presented a patient with several leishmania lesions who suffered from Systemic Lupus Erythematosus (SLE). He was a 22-year-old man from Fars province, southern Iran who was treated with corticosteroid drugs to control the manifestations of SLE. The presence of leishmanial bodies was confirmed by microscopic and molecular methods. Treatment was performed based on sodium antimony gluconate (1.5 mg/5ml) for three weeks, resulting in acceptable outcomes. However, recurrence of the lesions was observed after two months when the medication was discontinued. This was the first report of Zoonotic Cutaneous Leishmaniasis (ZCL) in an SLE patient.