Search results for: interferon alpha and beta receptor subunit 2

Authors: Ting-Chia Lien, Tzu-Yin Yen, Szu-Fan Chen, Tai-chun Kuo, Hung-Tse Lin, Yi-Chen Chung, Hock-Sen Gwee

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The purpose of this study was to explore the result of the survey by developing “Self-Concept Scale for Elders”, which could provide community counseling and guidance institution for practical application. The sample of this study consisted of 332 elders in Taiwan (male: 33.4%; female: 66.6%). The mean age of participants was 65-98 years. The measurements applied in this study is “Self-Concept Scale for Elders”. After item and factor analyses, the preliminary version of the Self-Concept Scale for Elders was revised to the final version. The results were summarized as follows: 1) There were 10 items in Self-Concept Scale for Elders. 2) The variance explained for the scale accounted for 77.15%, with corrected item-total correlations Cronbach’s alpha=0.87. 3) The content validity, criterion validity and construct validity have been found to be satisfactory. Based on the findings, the implication and suggestions are offered for reference regarding counselor education and future research.

Keywords: self-concept, elder, development scale, applied psychology

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Authors: Sudhir Kumar Sharma, Abiy D. Woldetsadik, Mazin Magzoub, Ramesh Jagannathan

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It is well known that bioactive ceramics exhibit specific biological affinities, especially in the area of tissue re-generation. In this context, we report the development of an eminently scalable, novel, supercritical CO₂ based process for the fabrication of hierarchically porous 'soft' CaCO₃ scaffolds. Porosity at the macro, micro, and nanoscales was obtained through process optimization of the so-called 'coffee-ring effect'. Exposure of these CaCO₃ scaffolds to monocytic THP-1 cells yielded negligible levels of tumor necrosis factor-alpha (TNF-α) thereby confirming the lack of immunogenicity of the scaffolds. ECM protein treatment of the scaffolds showed enhanced adsorption comparable to standard control such as glass. In vitro studies using osteoblast precursor cell line, MC3T3, also demonstrated the cytocompatibility of hierarchical porous CaCO₃ scaffolds.

Keywords: supercritical CO2, CaCO3 scaffolds, coffee-ring effect, ECM proteins

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Authors: Sara Pereira-Nogueira, Tim Worbs, Marc Permanyer-Bosser, Reinhold Förster

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While the entry mechanism of lymphocytes into the lymph node via the blood are well described, it is still largely unknown how cells enter lymph nodes that arrive via afferent lymphatics. In order to address this, our group has established a micro-injection technique in mice through which cells are delivered directly into the lymphatic vessel immediately afferent to the popliteal lymph node. Injected cells can then be tracked via multi-colour fluorescence or 2-photon microscopy, and their localization can be analysed within the popliteal or downstream lymph nodes by immunohistology. Since naïve B cells express the chemokine receptor CXCR5 we intra-lymphatically co-injected B cells derived from wildtype and Cxcr5-deficient mice. While CXCR5 does not play a role in guiding B cells out of the subcapsular sinus, it affects their positioning within the lymph node parenchyma, since CXCR5-deficient B cells are impaired in migrating into the B cell follicle. The knowledge obtained by studying B-cell migration may prove beneficial in clinical settings regarding tumor metastasis or autoimmune diseases.

Keywords: afferent lymphatics, B cell migration, chemokine, intra-lymphatic injection

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Authors: Sergei P. Efimov

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The anomalous magnetic moment of the electron is calculated by introducing the effective mass of the virtual part of the electron structure. In this case, the anomalous moment is inversely proportional to the effective mass Meff, which is shown to be a linear combination of the neutron, proton, and electrostatic electron field masses. The spin of a rotating structure is assumed to be equal to 3/2, while the spin of a 'bare' electron is equal to unity, the resultant spin being 1/2. A simple analysis gives the coefficients for a linear combination of proton and electron masses, the approximation precision giving here nine significant digits after the decimal point. The summand proportional to α² adds four more digits. Thus, the conception of the effective mass Meff leads to the formula for the total magnetic moment of the electron, which is accurate to fourteen digits. Association with the virtual beta-decay reaction and possible reasons for simplicity of the derived formula are discussed.

Keywords: anomalous magnetic moment of electron, comparison with quantum electrodynamics. effective mass, fifteen significant figures, proton and neutron masses

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Authors: Swati Gautam, Salman Akhtar, S. P. Jaiswar, Amita Jain

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Background: FGTB is now a major global health problem mostly in developing countries including India. In humans, Mycobacterium Tuberculosis (M.tb) is a causating agent of infection. High index of suspicion is required for early diagnosis due to asymptomatic presentation of FGTB disease. In macrophages Toll Like Receptor-2 (TLR-2) is one which mediated host’s immune response to M.tb. The expression of TLR-2 on macrophages is important to determine the fate of innate immune responses to M.tb. TLR-2 have two work. First its high expression on macrophages worsen the outer of infection and another side, it maintains M.tb to its dormant stage avoids activation of M.tb from latent phase. Single Nucleotide Polymorphism (SNP) of TLR-2 gene plays an important role in susceptibility to TB among different populations and subsequently, in the development of infertility. Methodology: This Case-Control study was done in the Department of Obs and Gynae and Department of Microbiology at King George’s Medical University, U.P, Lucknow, India. Total 300 subjects (150 Cases and 150 Controls) were enrolled in the study. All subjects were enrolled only after fulfilling the given inclusion and exclusion criteria. Inclusion criteria: Age 20-35 years, menstrual-irregularities, positive on Acid-Fast Bacilli (AFB), TB-PCR, (LJ/MGIT) culture in Endometrial Aspiration (EA). Exclusion criteria: Koch’s active, on ATT, PCOS, and Endometriosis fibroid women, positive on Gonococal and Chlamydia. Blood samples were collected in EDTA tubes from cases and healthy control women (HCW) and genomic DNA extraction was carried out by salting-out method. Genotyping of TLR2 genetic variants (Arg753Gln and Arg677Trp) were performed by using single amplification refractory mutation system (ARMS) PCR technique. PCR products were analyzed by electrophoresis on 1.2% agarose gel and visualized by gel-doc. Statistical analysis of the data was performed using the SPSS 16.3 software and computing odds ratio (OR) with 95% CI. Linkage Disequiliribium (LD) analysis was done by SNP stats online software. Results: In TLR-2 (Arg753Gln) polymorphism significant risk of FGTB observed with GG homozygous mutant genotype (OR=13, CI=0.71-237.7, p=0.05), AG heterozygous mutant genotype (OR=13.7, CI=0.76-248.06, p=0.03) however, G allele (OR=1.09, CI=0.78-1.52, p=0.67) individually was not associated with FGTB. In TLR-2 (Arg677Trp) polymorphism a significant risk of FGTB observed with TT homozygous mutant genotype (OR= 0.020, CI=0.001-0.341, p < 0.001), CT heterozygous mutant genotype (OR=0.53, CI=0.33-0.86, p=0.014) and T allele (OR=0.463, CI=0.32-0.66, p < 0.001). TT mutant genotype was only found in FGTB cases and frequency of CT heterozygous more in control group as compared to FGTB group. So, CT genotype worked as protective mutation for FGTB susceptibility group. In haplotype analysis of TLR-2 genetic variants, four possible combinations, i.e. (G-T, A-C, G-C, and A-T) were obtained. The frequency of haplotype A-C was significantly higher in FGTB cases (0.32). Control group did not show A-C haplotype and only found in FGTB cases. Conclusion: In conclusion, study showed a significant association with both genetic variants of TLR-2 of FGTB disease. Moreover, the presence of specific associated genotype/alleles suggest the possibility of disease severity and clinical approach aimed to prevent extensive damage by disease and also helpful for early detection of disease.

Keywords: ARMS, EDTA, FGTB, TLR

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Authors: Kseniya Gladun

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Tactile stimulation of a dorsal side of the wrist can have a strong impact on our attitude toward physical objects such as pleasant and unpleasant impact. This study explored different aspects of tactile perception to investigate atypical touch sensitivity in children with autism spectrum disorder (ASD). This study included 40 children with ASD and 40 healthy children aged 5 to 9 years. We recorded rsEEG (sampling rate of 250 Hz) during 20 min using EEG amplifier “Encephalan” (Medicom MTD, Taganrog, Russian Federation) with 19 AgCl electrodes placed according to the International 10–20 System. The electrodes placed on the left, and right mastoids served as joint references under unipolar montage. The registration of EEG v19 assignments was carried out: frontal (Fp1-Fp2; F3-F4), temporal anterior (T3-T4), temporal posterior (T5-T6), parietal (P3-P4), occipital (O1-O2). Subjects were passively touched by 4 types of tactile stimuli on the left wrist. Our stimuli were presented with a velocity of about 3–5 cm per sec. The stimuli materials and procedure were chosen for being the most "pleasant," "rough," "prickly" and "recognizable". Type of tactile stimulation: Soft cosmetic brush - "pleasant" , Rough shoe brush - "rough", Wartenberg pin wheel roller - "prickly", and the cognitive tactile stimulation included letters by finger (most of the patient’s name ) "recognizable". To designate the moments of the stimuli onset-offset, we marked the moment when the moment of the touch began and ended; the stimulation was manual, and synchronization was not precise enough for event-related measures. EEG epochs were cleaned from eye movements by ICA-based algorithm in EEGLAB plugin for MatLab 7.11.0 (Mathwork Inc.). Muscle artifacts were cut out by manual data inspection. The response to tactile stimuli was significantly different in the group of children with ASD and healthy children, which was also depended on type of tactile stimuli and the severity of ASD. Amplitude of Alpha rhythm increased in parietal region to response for only pleasant stimulus, for another type of stimulus ("rough," "thorny", "recognizable") distinction of amplitude was not observed. Correlation dimension D2 was higher in healthy children compared to children with ASD (main effect ANOVA). In ASD group D2 was lower for pleasant and unpleasant compared to the background in the right parietal area. Hilbert transform changes in the frequency of the theta rhythm found only for a rough tactile stimulation compared with healthy participants only in the right parietal area. Children with autism spectrum disorders and healthy children were responded to tactile stimulation differently with specific frequency distribution alpha and theta band in the right parietal area. Thus, our data supports the hypothesis that rsEEG may serve as a sensitive index of altered neural activity caused by ASD. Children with autism have difficulty in distinguishing the emotional stimuli ("pleasant," "rough," "prickly" and "recognizable").

Keywords: autism, tactile stimulation, Hilbert transform, pediatric electroencephalography

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Authors: M. Mousavi-Daramoroudi, H. Yousefnia, F. Abbasi-Davani, S. Zolghadri, S. Kakaei

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Despite the appropriate characteristics of ¹⁷⁷Lu and DOTATOC, to our best knowledge, the therapeutic benefit of ¹⁷⁷Lu-DOTATOC complex in breast cancer has not been reported until now. In this study, biodistribution of ¹⁷⁷Lu-DOTA-TOC in mouse tumor model for evaluation of possible utilization of this complex in breast cancer treatment was investigated.¹⁷⁷Lu was prepared with the specific activity of 2.6-3 GBq.mg^-1 and radionuclidic purity higher than 99%. The radiolabeled complex was prepared in the optimized conditions with the radiochemical purity higher than 99%. The final solution was injected to the BALB/c mice with adenocarcinoma breast cancer. The biodistribution results showed major accumulation in the kidneys as the major excretion route and the somatostatin receptor-positive tissues such as pancreas compared with the other tissues. Also, significant uptake was observed in tumor even in longer time after injection. According to the results obtained in this research study, somatostatin receptors expressed in breast cancers can be targeted with DOTATOC analogues especially with ¹⁷⁷Lu-DOTATOC as an ideal therapeutic agent.

Keywords: ¹⁷⁷Lu, adenocarcinoma breast cancer, DOTATOC, BALB/c mice

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Authors: Junaid Mahmood Alam, Sana Anwar, Sarah Sughra Asghar

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Chronic hepatitis or Hepatitis C viral (HCV) infection has been identified as one of the factors that could elicit autoimmune disease resulting in the development of auto-antibodies. Furthermore, HCV is implicated in contravening of forbearance to antigens, therefore, inciting auto-reactivity. In this regard, several near and past studies noted the prevalence of thyroid dysfunction and production of anti-thyroid antibodies (ATAb) such as anti-thyroid peroxidase (AntiTPO) and anti-thyroglobulin (AntiTG) in patients with HCV. Likewise, one of the etiologies of augmentation of thyroid disease is basically interferon therapy for HCV infections, for which a number of autoimmune diseases have been noted including Grave’s disease, Hishimoto thyroiditis. A prospectively case-control study was therefore carried out at department of clinical biochemistry lab services and chemical pathology in collaboration with department of clinical microbiology, at Liaquat National Hospital and Medical College, Karachi Pakistan for the period January 2015 to December 2017. Two control groups were inducted for comparison purpose, control group 1 = without HCV infection and with thyroid disorders (n = 20), control group 2 = with HCV infection and without thyroid disorders (n = 20), whereas HCV infected were n = 40 where more than half were noted to be positive for either of HCV IgG and Ag. In HCV group, patients with existing sub-clinical hypothyroidism and clinical hyperthyroidism were less than 5%. Analysis showed the presence of AntiTG in 12 HCV patients (30%), AntiTPO in 15 (37.5%) and both AntiTG and antiTPO in 10 patients (25%). Only 3 patients were found with the history of anti-thyroid auto-antibodies (7.5%) and one with parents and relatives with auto-immune disorders (2.5%). Patients that remained untreated were 12 (30%), under treatment 18 (45%) and with complete-course of treatment 10 (25%). As per review of the literature, meta-analysis of evident data and cross-sectional studies of selective cohorts (as studied in presented research), thyroid connection is designated as one of the most recurrent endocrine ailment associated with chronic HCV infection. Moreover, it also represents an extrahepatic disease in the continuum of HCV syndrome. In conclusion, HCV patients were more likely to encompass thyroid disorders especially related to development of either of ATAb or both antiTG and AntiTPO.

Keywords: Hepatitis C viral (HCV) infection, anti-thyroid antibodies, anti-thyroid peroxidase antibodies, anti-thyroglobulin antibodies

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Authors: Hong Su, Qiuju Yan, Wei Du, En Hu, Zhaoyu Yang, Wei Zhang, Yusheng Li, Tao Tang, Wang yang, Shushan Zhao

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Osteoarthritis (OA) is a severe chronic inflammatory disease. As the main active component of Astragalus mongholicus Bunge, a classic traditional ethnic herb, calycosin exhibits anti-inflammatory action and its mechanism of exact targets for OA have yet to be determined. In this study, we established an anterior cruciate ligament transection (ACLT) mouse model. Mice were randomized to sham, OA, and calycosin groups. Cartilage synthesis markers type II collagen (Col-2) and SRY-Box Transcription Factor 9 (Sox-9) increased significantly after calycosin gavage. While cartilage matrix degradation index cyclooxygenase-2 (COX-2), phosphor-epidermal growth factor receptor (p-EGFR), and matrix metalloproteinase-9 (MMP9) expression were decreased. With the help of network pharmacology and molecular docking, these results were confirmed in chondrocyte ATDC5 cells. Our results indicated that the calycosin treatment significantly improved cartilage damage, this was probably attributed to reversing the imbalance between chondrocyte synthesis and catabolism.

Keywords: calycosin, osteoarthritis, network pharmacology, molecular docking, inflammatory, cyclooxygenase 2

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Authors: Sundus Mona, Atif Adnan, Babar Ali, Fareeha Arshad, Allah Rakha

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Molecular diversity is the variation in the abundance of species. Forensic entomology is a neglected field in Pakistan. Insects collected from the crime scene should be handled by forensic entomologists who are currently virtually non-existent in Pakistan. Correct identification of insect specimen along with knowledge of their biodiversity can aid in solving many problems related to complicated forensic cases. Inadequate morphological identification and insufficient thermal biological studies limit the entomological utility in Forensic Medicine. Recently molecular identification of entomological evidence has gained attention globally. DNA barcoding is the latest and established method for species identification. Only proper identification can provide a precise estimation of postmortem intervals. Arthropods are known to be the first tourists scavenging on decomposing dead matter. The objective of the proposed study was to identify species by molecular techniques and analyze their phylogenetic importance with barcoded necrophagous insect species of early succession on human cadavers. Based upon this identification, the study outcomes will be the utilization of established DNA bar codes to identify carrion feeding insect species for concordant estimation of post mortem interval. A molecular identification method involving sequencing of a 658bp ‘barcode’ fragment of the mitochondrial cytochrome oxidase subunit 1 (CO1) gene from collected specimens of unknown dipteral species from cadavers of Lahore was evaluated. Nucleotide sequence divergences were calculated using MEGA 7 and Arlequin, and a neighbor-joining phylogenetic tree was generated. Three species were identified, Chrysomya megacephala, Chrysomya saffranea, and Chrysomya rufifacies with low genetic diversity. The fixation index was 0.83992 that suggests a need for further studies to identify and classify forensically relevant insects in Pakistan. There is an exigency demand for further research especially when immature forms of arthropods are recovered from the crime scene.

Keywords: molecular diversity, DNA barcoding, species identification, forensically relevant

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Authors: Maciej Sobczak, Julita Pietrzak, Tomasz Płoszaj, Agnieszka Robaszkiewicz

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Brg1, a member of SWI/SNF complex, plays a role in chromatin remodeling, therefore, regulates expression of many genes. Brg1 is an ATPase of SWI/SNF complex, thus its activity requires ATP. Through its bromodomain recognizes acetylated histone residues and evicts them, thus promoting transcriptionally active state of chromatin. One of the enzymes that is responsible for acetylation of histone residues is Ep300. It was previously shown in the literature that cooperation of Brg1 and Ep300 occurs at the promoter regions that have binding sites for E2F-family transcription factors as well as CpG islands. According to literature, approximately 20% of human cancer possess mutation in Brg1 or any other crucial SWI/SNF subunit. That phenomenon makes Brg1-Ep300 a very promising target for anti-cancer therapy. Therefore in our study, we investigated if physical interaction between Brg1 and Ep300 exists and what impact those two proteins have on key for breast cancer cells processes such as DNA damage repair and cell proliferation. Bioinformatical analysis pointed out, that genes involved in cell proliferation and DNA damage repair are overexpressed in MCF7 and MDA-MB-231 cells. Moreover, promoter regions of these genes are highly acetylated, which suggests high transcriptional activity of those sites. Notably, many of those gene possess within their promoters an E2F, Brg1 motives, as well as CpG islands and acetylated histones. Our data show that Brg1 physically interacts with Ep300, and together they regulate expression of genes involved in DNA damage repair and cell proliferation. Upon inhibiting Brg1 or Ep300, expression of vital for cancer cell survival genes such as CDK2/4, BRCA1/2, PCNA, and XRCC1 is decreased in MDA-MB-231 and MCF7 cells. Moreover, inhibition or silencing of either Brg1 or Ep300 leads to cell cycle arrest in G1. After inhibition of BRG1 or Ep300 on tested gene promoters, the repressor complex including Rb, HDAC1, and EZH2 is formed, which inhibits gene expression. These results highlight potentially significant target for targeted anticancer therapy to be introduced as a supportive therapy.

Keywords: brg1, ep300, breast cancer, epigenetics

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Authors: Laura Bellassen, Idit Shachar

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Multiple sclerosis (MS) is a chronic neurological disorder characterized by demyelination of the central nervous system (CNS), leading to a wide range of physical and cognitive impairments. Myeloid cells in the CNS, such microglia and border associated macrophage cells, participate in the neuroinflammation in MS. Activation of those cells in MS contributes to the inflammatory response in the CNS and recruitment of immune cells in the this compartment. SLAMF5 is a cell surface receptor that functions as a homophilic adhesion molecule, whose signaling can activate or inhibit leukocyte function. In the current study we followed the expression and function of SLAMF5 in myeloid cells in the CNS and in the periphery in the murine model for MS, the experimental autoimmune encephalomyelitis model (EAE). Our results show that SLAMF5 deficiency or blocking decreases the expression of activation molecules and costimulatory molecules such as MHCII and CD80, resulting in delayed onset and reduced progression of the disease. Moreover, blocking SLAMF5 in peripheral monocytes derived from MS patients and iPSC-derived microglia cells, controls the expression of HLA-DR and CD80. Thus, SLAMF5 is a regulator of myeloid cells function and can serve as a therapeutic target in autoimmune disorders as Multiple Sclerosis.

Keywords: multiple sclerosis, EAE model, myeloid cells, new antibody, neuroimmunology

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Authors: Sabahattin Comertpay, Sandra Pastorino, Rosanna Mezzapelle, Mika Tanji, Oriana Strianese, Andrea Napolitano, Tracey Weigel, Joseph Friedberg, Paul Sugarbaker, Thomas Krausz, Ena Wang, Amy Powers, Giovanni Gaudino, Harvey I. Pass, Fatmagul Ozcelik, Barbara L. Parsons, Haining Yang, Michele Carbone

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Tumors are thought to be monoclonal in origin. This paradigm arose decades ago, primarily from the study of hematopoietic malignancies and sarcomas. The clonal origin of malignant mesothelioma (MM), a deadly cancer resistant to the current therapies, has not been investigated. Examination of the pleura from patients with MM shows often the presence of multiple pleural nodules, raising the question of whether they represent independent or metastatic growth processes. To investigate the clonality patterns of MM, we used the HUMARA (Human Androgen Receptor) assay to examine 14 sporadic and 2 familial Malignant Mesotheliomas (MM). Of 16 specimens studied, 15 were informative and 14/15 revealed two electrophoretically distinct methylated HUMARA alleles, indicating a polyclonal origin for these tumors. This discovery has important clinical implications, because an accurate assessment of tumor clonality is key to the design of novel molecular strategies for the treatment of MM.

Keywords: malignant mesothelioma, clonal origin, HUMARA, sarcomas

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Authors: Regina M. Chiechio, Rémi Leguevél, Helene Solhi, Marie Madeleine Gueguen, Stephanie Dutertre, Xavier, Jean-Pierre Bazureau, Olivier Mignen, Pascale Even-Hernandez, Paolo Musumeci, Maria Jose Lo Faro, Valerie Marchi

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Thanks to their ultra-small size, high electron density, and low toxicity, gold nanoclusters (Au NCs) have unique photoelectrochemical and luminescence properties that make them very interesting for diagnosis bio-imaging and theranostics. These applications require control of their delivery and interaction with cells; for this reason, the surface chemistry of Au NCs is essential to determine their interaction with the targeted biological objects. Here we demonstrate their ability as markers of pancreatic tumor cells. By functionalizing the surface of the NCs with a recognition peptite (U11), the nanostructures are able to preferentially bind to pancreatic cancer cells via a receptor (uPAR) overexpressed by these cells. Furthermore, the NCs can mark even the nucleus without the need of fixing the cells. These nanostructures can therefore be used as a non-toxic, multivalent luminescent platform, capable of selectively recognizing tumor cells for bioimaging, drug delivery, and radiosensitization.

Keywords: gold nanoclusters, luminescence, biomarkers, pancreatic cancer, biomedical applications, bioimaging, fluorescent probes, drug delivery

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Authors: Michal Kielbik, Izabela Szulc-Kielbik, Anna Brzostek, Jaroslaw Dziadek, Magdalena Klink

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The goal of many research groups in the world is to find new components that are important for survival of mycobacteria in the host cells. Mycobacterium tuberculosis (Mtb) possesses a number of enzymes degrading cholesterol that are considered to be an important factor for its survival and persistence in host macrophages. One of them - cholesterol oxidase (ChoD), although not being essential for cholesterol degradation, is discussed as a virulence compound, however its involvement in macrophages’ response to Mtb is still not sufficiently determined. The recognition of tubercle bacilli antigens by pathogen recognition receptors is crucial for the initiation of the host innate immune response. An important receptor that has been implicated in the recognition and/or uptake of Mtb is Toll-like receptor type 2 (TLR2). Engagement of TLR2 results in the activation and phosphorylation of intracellular signaling proteins including IRAK-1 and -4, TRAF-6, which in turn leads to the activation of target kinases and transcription factors responsible for bactericidal and pro-inflammatory response of macrophages. The aim of these studies was a detailed clarification of the role of Mtb cholesterol oxidase as a virulence factor affecting the TLR2 signaling pathway in human macrophages. As human macrophages the THP-1 differentiated cells were applied. The virulent wild-type Mtb strain (H37Rv), its mutant lacking a functional copy of gene encoding cholesterol oxidase (∆choD), as well as complimented strain (∆choD–choD) were used. We tested the impact of Mtb strains on the expression of TLR2-depended signaling proteins (mRNA level, cytosolic level and phosphorylation status). The cytokine and bactericidal response of THP-1 derived macrophages infected with Mtb strains in relation to TLR2 signaling pathway dependence was also determined. We found that during the 24-hours of infection process the wild-type and complemented Mtb significantly reduced the cytosolic level and phosphorylation status of IRAK-4 and TRAF-6 proteins in macrophages, that was not observed in the case of ΔchoD mutant. Decreasement of TLR2-dependent signaling proteins, induced by wild-type Mtb, was not dependent on the activity of proteasome. Blocking of TLR2 expression, before infection, effectively prevented the induced by wild-type strain reduction of cytosolic level and phosphorylation of IRAK-4. None of the strains affected the surface expression of TLR2. The mRNA level of IRAK-4 and TRAF-6 genes were significantly increased in macrophages 24 hours post-infection with either of tested strains. However, the impact of wild-type Mtb strain on both examined genes was significantly stronger than its ΔchoD mutant. We also found that wild-type strain stimulated macrophages to release high amount of immunosuppressive IL-10, accompanied by low amount of pro-inflammatory IL-8 and bactericidal nitric oxide in comparison to mutant lacking cholesterol oxidase. The influence of wild-type Mtb on this type of macrophages' response strongly dependent on fully active IRAK-1 and IRAK-4 signaling proteins. In conclusion, Mtb using cholesterol oxidase causes the over-activation of TLR2 signaling proteins leading to the reduction of their cytosolic level and activity resulting in the modulation of macrophages response to allow its intracellular survival. Supported by grant: 2014/15/B/NZ6/01565, National Science Center, Poland

Keywords: Mycobacterium tuberculosis, cholesterol oxidase, macrophages, TLR2-dependent signaling pathway

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Authors: Mukurdipi Ray, Seema Singh

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Extrauterine endometrial stromal sarcoma (ESS) is a rare entity and typified by delayed recurrence of primary ESS. Here, we present an unusual case of uterine ESS in a woman with a history of hysterectomy. A 19-year-old girl, underwent a hysterectomy and bilateral salpingo-oophorectomy for uterine ESS 12 months ago and now after remaining disease free for nine months ago she presented with ascites along with pelvic and peritoneal mass. Intraoperatively, the large omental mass was found, and optimal cytoreduction with total omentomy (supracolic and infracolic ) total peritonectomy and hyperthermic intraperitoneal chemotherapy (HIPEC) was offered to the patient. Final histopathology report showed the involvement of only omentum by ESS cells. Immunohistochemistry (IHC) and receptor study were done and it was positive for CD-10 and desmin and negative for CK- 7. This case highlights the rarity of extrauterine ESS in the omentum with a known history of primary uterine ESS which was treated successfully with the above-mentioned procedure. Though active and long-term surveillance is recommended to monitor for late recurrences.

Keywords: endrometrial stromal sarcoma, complete cytoreduction, hyperthermic intra peritoneal chemotherapy, total omentectomy

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Authors: Mehrnaz Mostafavi, Mahtab Shabani, Alireza Azani, Fatemeh Ghafari

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Artificial intelligence (AI) can transform breast cancer diagnosis and therapy by providing sophisticated solutions for screening, imaging interpretation, histopathological analysis, and treatment planning. This literature review digs into the many uses of AI in breast cancer treatment, highlighting the need for collaboration between AI scientists and healthcare practitioners. It emphasizes advances in AI-driven breast imaging interpretation, such as computer-aided detection and diagnosis (CADe/CADx) systems and deep learning algorithms. These have shown significant potential for improving diagnostic accuracy and lowering radiologists' workloads. Furthermore, AI approaches such as deep learning have been used in histopathological research to accurately predict hormone receptor status and categorize tumor-associated stroma from regular H&E stains. These AI-powered approaches simplify diagnostic procedures while providing insights into tumor biology and prognosis. As AI becomes more embedded in breast cancer care, it is crucial to ensure its ethical, efficient, and patient-focused implementation to improve outcomes for breast cancer patients ultimately.

Keywords: breast cancer, artificial intelligence, cancer diagnosis, clinical practice

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Authors: Jahanshah Ashkani, Kevin J. Naidoo

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Glycosylation is the major posttranslational modification (PTM) process in cellular development. In tumour development, it is marked by structural alteration of carbohydrates (glycans) that is the result of aberrant glycosylation. Altered glycan structures affect cell surface ligand-receptor interactions that interfere with the regulation of cell adhesion, migration, and proliferation. The resulting changes in glycan biosynthesis pathways originate from altered expression of glycosyltransferases and glycosidases. While the alteration in glycosylation patterns is a recognized “hallmark of cancer”, the influential overview of the biology of cancer proposes eight hallmarks with no explicit suggestion to connectivity with glycosylation. Recently, we have discovered a connection between the glycosyltransferase gene expression and cancer type and subtype. Here we present an association between aberrant glycosylation and the biological hallmarks of breast cancer by exploring the common regulatory mechanisms at the genomic scale. The result of this study bridges the glycobiological and biological pathways that are accepted hallmarks of cancer by connecting their common regulatory pathways. This is an impetus for further investigation as target therapies of breast cancer are very likely to be uncovered from this.

Keywords: aberrant glycosylation, biological hallmarks, breast cancer, regulatory mechanism

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Authors: F. Loffredo, M. Quarto, M. Pugliese, A. Mazzella, F. De Cicco, V. Roca

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The aim of this study is to evaluate the efficacy of radon remedial action in a school on the Ischia island, South Italy, affected by indoor radon concentration higher than the value of 500 Bq/m³. This value is the limit imposed by the Italian legislation, to above which corrective actions in schools are necessary. Before the application of remedial action, indoor radon concentrations were measured in 9 rooms of the school. The measurements were performed with LR-115 passive alpha detectors (SSNTDs) and E-Perm. The remedial action was conducted in one of the office affected by high radon concentration using a Radonstop paint applied after the construction of a concrete slab under the floor. The effect of remedial action was the reduction of the concentration of radon of 41% and moreover it has demonstrated to be durable over time. The chosen method is cheap and easy to apply and it could be designed for various types of building. This method can be applied to new and existing buildings that show high dose values.

Keywords: E-Perm, LR 115 detectors, radon remediation, school

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Authors: Shikha Masand, Sudesh Kumar Yadav

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Certain protein kinases have been shown to be crucial for plant cell signaling pathways associated with plant immune responses. Here we identified a horsegram [Macrotyloma uniflorum (Lam.) Verdc.] malectin-like leucine rich receptor-like protein kinase (RLK) gene MuRLK. The functional MuRLK protein preferentially binds to mannose and N-acetyl glucosamine residues. MuRLK exists in the cytoplasm and also localizes to the plasma membrane of plant cells via its N-terminus. Over-expression of MuRLK in Arabidopsis enhances the basal resistance to infection with Pseudomonas syringae pv. tomato, Alternaria brassicicola and Hyaloperonospora arabidopsidis, are associated with elevated ROS bursts, MAPK activation, thus ultimately leading to hypersensitive cell death. Moreover, salicylic acid-dependent and jasmonic acid-dependent defense responses are also enhanced in the MuRLK-overexpressed plants that lead to HR-induced cell death. Together, these results suggest that MuRLK plays a key role in the regulation of plant cell death, early and late defense responses after the recognition of microbial pathogens.

Keywords: horsegram, Pseudomonas syringae pv. tomato, MuRLK, ROS burst, cell death, plant defense

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Authors: Jeremy J. Johnson

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Mediterranean herbs including rosemary (Rosmarinus officinalis) contain a variety of phytochemicals including diterpenes that possess extensive biological activity. Applications of diterpenes, including the more abundant forms carnosol and carnosic acid, have been shown to possess anti-cancer, anti-inflammatory, anti-oxidant, and anti-proliferation properties. To confirm these properties, we have evaluated rosemary extract and selected diterpenes for biological activity in cancer and inflammatory models. Our preliminary data have revealed that select diterpenes can disrupt androgen receptor functionality in prostate and breast cancer cells. This property is unique among natural products for hormone-responsive cancers. The second area of interest has been evaluating rosemary extract and selected diterpenes for activation of sestrin-2, an antioxidant protein, in colon cancer cells. A combination of in vitro and in vivo approaches have been utilized to characterize the activity of rosemary diterpenes in rosemary. Taken together, these results suggest that phytochemicals found in rosemary have distinct pharmacological actions for disrupting cell-signaling pathways in cancer and inflammatory bowel disease.

Keywords: rosemary, diterpene, cancer, inflammation

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Authors: Suttipong Phosuksirikul, Rawichar Chaipojjana, Arunsri Leejeerajumnean

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The aim of research was to define the relations between volatile compounds, some parameters (pH, titratable acidity (TA), total soluble solid (TSS), lactic acid bacteria count) and consumer preference of commercial fermented milks. These relations tend to be used for controlling and developing new fermented milk product. Three leading commercial brands of fermented milks in Thailand were evaluated by consumers (n=71) using hedonic scale for four attributes (sweetness, sourness, flavour, and overall liking), volatile compounds using headspace-solid phase microextraction (HS-SPME) GC-MS, pH, TA, TSS and LAB count. Then the relations were analyzed by principal component analysis (PCA). The PCA data showed that all of four attributes liking scores were related to each other. They were also related to TA, TSS and volatile compounds. The related volatile compounds were mainly on fermented produced compounds including acetic acid, furanmethanol, furfural, octanoic acid and the volatiles known as artificial fruit flavour (beta pinene, limonene, vanillin, and ethyl vanillin). These compounds were provided the information about flavour addition in commercial fermented milk in Thailand.

Keywords: fermented milk, volatile compounds, preference, PCA

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Authors: Jann-Eike Saathoff, Kirill Alexander Schmoor, Martin Achmus, Mauricio Terceros

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By using partial factors of safety, uncertainties due to the inherent variability of the soil properties and loads are taken into account in the geotechnical design process. According to the reliability index concept in Eurocode-0 in conjunction with Eurocode-7 a minimum safety level of β = 3.8 for reliability class RC2 shall be established. The reliability of the system depends heavily on the choice of the prespecified safety factor and the choice of the characteristic soil properties. The safety factors stated in the standards are mainly based on experience. However, no general accepted method for the calculation of a characteristic value within the current design practice exists. In this study, a laterally loaded monopile is investigated and the influence of the chosen quantile values of the deterministic system, calculated with p-y springs, will be presented. Monopiles are the most common foundation concepts for offshore wind energy converters. Based on the calculations for non-cohesive soils, a recommendation for an appropriate quantile value for the necessary safety level according to the standards for a deterministic design is given.

Keywords: asymptotic sampling, characteristic value, monopile foundation, probabilistic design, quantile values

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Authors: Hana Barak, Alex Sivan, Ariel Kushmaro

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Microorganisms are the most diverse and abundant life forms on Earth and account for a large portion of the Earth’s biomass and biodiversity. To date though, our knowledge regarding microbial life is lacking, as it is based mainly on information from cultivated organisms. Indeed, microbiologists have borrowed from astrophysics and termed the ‘uncultured microbial majority’ as ‘microbial dark matter’. The realization of how diverse and unexplored microorganisms are, actually stems from recent advances in molecular biology, and in particular from novel methods for sequencing microbial small subunit ribosomal RNA genes directly from environmental samples termed next-generation sequencing (NGS). This has led us to use NGS that generates several gigabases of sequencing data in a single experimental run, to identify and classify environmental samples of microorganisms. In metagenomics sequencing analysis (both 16S and shotgun), sequences are compared to reference databases that contain only small part of the existing microorganisms and therefore their taxonomy assignment may reveal groups of unknown microorganisms or origins. These unknowns, or the ‘microbial sequences dark matter’, are usually ignored in spite of their great importance. The goal of this work was to develop an improved bioinformatics method that enables more complete analyses of the microbial communities in numerous environments. Therefore, NGS was used to identify previously unknown microorganisms from three different environments (industrials wastewater, Negev Desert’s rocks and water wells at the Arava valley). 16S rRNA gene metagenome analysis of the microorganisms from those three environments produce about ~4 million reads for 75 samples. Between 0.1-12% of the sequences in each sample were tagged as ‘Unassigned’. Employing relatively simple methodology for resequencing of original gDNA samples through Sanger or MiSeq Illumina with specific primers, this study demonstrates that the mysterious ‘Unassigned’ group apparently contains sequences of candidate phyla. Those unknown sequences can be located on a phylogenetic tree and thus provide a better understanding of the ‘sequences dark matter’ and its role in the research of microbial communities and diversity. Studying this ‘dark matter’ will extend the existing databases and could reveal the hidden potential of the ‘microbial dark matter’.

Keywords: bacteria, bioinformatics, dark matter, Next Generation Sequencing, unknown

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Authors: Elham Taghizade Sigarodi, Ani Mirzakhanian

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Journalism atmosphere in present era is highly competitive so that what matters the most is “the speed of news broadcasting”. The first newspaper that lets out the news is therefore of higher validity. The value of the news is in fact in its truthfulness. Expressing the facts and reality is an accepted norm in professional media arena and it is as well considered the acceptable and trustworthy language for journalism. However, different conditions generate self-censorship. The present study seeks to explore the relationship between self-censorship and satisfaction of Iran newspaper’s readers. Thus, the statistical population including journalists of Iran newspaper for Tehran’s readers was estimated 384 persons based on Morgan table. Through cluster sampling, 50 journalists were selected so that totally the sample size was 434 persons and questionnaire was applied for data analysis and based on Alpha Chronbache, it was supported. Through Pierson correlation, the main and all subsidiary hypotheses were supported except the forth one.

Keywords: newspaper, satisfaction of audiences, self-censorship, journalists

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Authors: Muhammad Nauman Ahmad, Patrick Büker, Sofia Khalid, Leon Van Den Berg, Hamid Ullah Shah, Abdul Wahid, Lisa Emberson, Sally A. Power, Mike Ashmore

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Although ozone is well-documented to affect crop yields in the densely populated Indo-Gangetic Plain, there is little knowledge of its effects around cities in more remote areas of South Asia. We surveyed crops around the city of Peshawar, Pakistan for visible injury, linking this to passive measurements of ozone concentrations. Foliar injury was found in the field on potato, onion and cotton when the mean monthly ozone concentration reached 35-55ppb. The symptoms on onion were reproduced in ozone fumigation experiments, which also showed that daytime ozone concentrations of 60ppb and above significantly reduce the growth of Pakistani varieties of both spinach (Beta vulgaris) and onion. Aphid infestation on spinach was also reduced at these elevated ozone concentrations. The ozone concentrations in Peshawar are comparable to those through many parts of northern south Asia, where ozone may therefore be a significant threat to sensitive vegetable crops in peri-urban regions.

Keywords: ozone, air pollution, vegetable crops, peshawar, south asia

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Authors: Abida Mariam, Anwaar Ahmed, Asif Ahmad, Muhammad Sheeraz Ahmad, Muhammad Akram Khan, Muhammad Mazahir

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The plant olive (Olea europaea L.) is known for its commercial significance due to nutritional and health benefits. Pakistan is ranked 4th among countries who import olive oil whereas, 70% of edible oil is imported to fulfil the needs of the country. There exists great potential for Olea europaea cultivation in Pakistan. The popularity and cultivation of olive fruit has increased in recent past due to its high socio-economic and health significance. There exist almost negligible data on the chemical composition of extra virgin olive oil extracted from cultivars grown in Pothwar, an area with arid climate conducive for growth of olive trees. Keeping in view these factors a study has been conducted to characterize the olive oil extracted from olive cultivars collected from Pothwar regions of Pakistan for their nutritional potential and value addition. Ten olive cultivars (Gemlik, Coratina, Sevillano, Manzanilla, Leccino, Koroneiki, Frantoio, Arbiquina, Earlik and Ottobratica) were collected from Barani Agriculture Research Institute, Chakwal. Extra Virgin Olive Oil (EVOO) was extracted by cold pressing and centrifuging of olive fruits. The highest amount of oil was yielded in Coratina (23.9%) followed by Frantoio (23.7%), Koroneiki (22.8%), Sevillano (22%), Ottobratica (22%), Leccino (20.5%), Arbiquina (19.2%), Manzanilla (17.2%), Earlik (14.4%) and Gemllik (13.1%). The extracted virgin olive oil was studied for various physico- chemical properties and fatty acid profile. The Physical and chemical properties i.e., characteristic odor and taste, light yellow color with no foreign matter, insoluble impurities (≤0.08), fee fatty acid (0.1 to 0.8), acidity (0.5 to 1.6 mg/g acid), peroxide value (1.5 to 5.2 meqO2/kg), Iodine value (82 to 90), saponification value (186 to 192 mg/g) and unsaponifiable matter (4 to 8g/kg), ultraviolet spectrophotometric analysis (k232 and k270), showed values in the acceptable range, established by PSQCA and IOOC set for extra virgin olive oil. Olive oil was analyzed by Near Infra-Red spectrophotometry (NIR) for fatty acids sin olive oils which were found as: palmitic, palmitoleic, stearic, oleic, linoleic and alpha-linolenic. Major fatty acid was Oleic acid in the highest percentage ranging from (55 to 66.1%), followed by linoleic (10.4 to 20.4%), palmitic (13.8 to 19.5%), stearic (3.9 to 4.4%), palmitoleic (0.3 to 1.7%) and alpha-linolenic (0.9 to 1.7%). The results were significant with differences in parameters analyzed for all ten cultivars which confirm that genetic factors are important contributors in the physico-chemical characteristics of oil. The olive oil showed superior physical and chemical properties and recommended as one of the healthiest forms of edible oil. This study will help consumers to be more aware of and make better choices of healthy oils available locally thus contributing towards their better health.

Keywords: characterization, extra virgin olive oil, oil yield, fatty acids

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Authors: Ubonrattan Phophatanachai, Phensri Thongphet, Weerawan Kerdtong

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The purposes of this study were to compare the ethical behavior regarding responsibility and polite manners of nursing students of Boromarajonani College of Nursing, Suratthani, Thailand before and after providing the activity session of ethical behavior development. The samples consisted of 103 sophomores in the academic year 2006. The tools were tested for reliability and content validity. The reliability of the Ethical Behavior Questionnaire measured by Cronbach’s alpha coefficient was 0.94. Data were analyzed using means, standard deviations, and dependent t-test. The findings were as follows: a) after the activity session, the mean scores of ethical behavior regarding responsibility and polite manners of nursing students increased from middle level to high level; b) mean scores of responsibilities and polite manners after the activity session were significantly higher than those before the session (t =28.36, p < .001; t =23.9, p < .001, respectively).

Keywords: development of ethical behavior, nursing students, health, nursing informatics

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Authors: S. Kassou, R. El Mrabet, A. Belaaraj, P. Guionneau, N. Hadi, T. Lamcharfi

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The organic–inorganic hybrid perovskite-like [C₆H₅C₂H₄NH₃]₂ZnCl₄ (PEA-ZnCl₄) was synthesized by saturated solutions method. X-ray powder diffraction, Raman spectroscopy, UV-visible transmittance, and capacitance meter measurements have been used to characterize the structure, the functional groups, the optical parameters, and the dielectric constants of the material. The material has a layered structure. The optical transmittance (T %) was recorded and applied to deduce the absorption coefficient (α) and optical band gap (Eg). The hybrid shows an insulator character with a direct band gap about 4.46 eV, and presents high dielectric constants up to a frequency of about 10⁵ Hz, which suggests a ferroelectric behavior. The reported optical and dielectric properties can help to understand the fundamental properties of perovskite materials and also to be used for optimizing or designing new devices.

Keywords: dielectric constants, optical band gap (eg), optical parameters, Raman spectroscopy, self-assembly organic inorganic hybrid

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Authors: Sabri Sudirman, Yuan-Hua Hsu, Zwe-Ling Kong

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Male reproductive dysfunction is predominantly due to insulin resistance and hyperglycemia result in inflammation and oxidative stress. Furthermore, nanotechnology provides an alternative approach to improve the bioavailability of natural active food ingredients. Therefore, the aim of this study were to investigate nanoencapsulated triterpenoids from petri-dish cultured Antrodia cinnamomea (PAC) nanoparticles whether it could increase the bioavailability; in addition, the anti-inflammatory and anti-oxidative effects could more effectively ameliorate the reproductive function of diabetic male rats. First, PAC encapsulated in chitosan-silica nanoparticles (Nano-PAC) were prepared by biosilicification method. Scanning electron micrographs confirm the average particle size is about 30 nm, and the encapsulation efficiency is 83.7% by HPLC. Diabetic male Sprague-Dawley rats were induced by high fat diet (40% kcal from fat) and streptozotocin (35 mg/kg). Nano-PAC was administered by oral gavage in three doses (4, 8 and 20 mg/kg) for 6 weeks. Besides, metformin (300 mg/kg) and nanoparticles (Nano) were treated as the positive and negative control respectively. Results indicated that 4 mg/kg Nano-PAC administration for 6 weeks improved hyperglycemia, insulin resistance, and also reduced advanced glycation end products in plasma. In addition, 8 mg/kg Nano-PAC ameliorated morphological of testicular seminiferous tubules, sperm morphology and motility, reactive oxygen species production and mitochondrial membrane potential. Moreover, 20 mg/kg Nano-PAC restored reproductive endocrine system function and increased KiSS-1 level in plasma. In plasma or testis anti-oxidant superoxide dismutase, glutathione peroxidase and catalase were increased whereas malondialdehyde, as well as pro-inflammatory cytokines tumor necrosis factor-α, interleukin-6, and interferon-gamma, decreased. Most importantly, 8 mg/kg Nano-PAC down-regulated the oxidative stress induced c-Jun N-terminal kinase (JNK) signaling pathway. Our study successfully nanoencapsulated PAC to form nanoparticles and low-dose Nano-PAC improved diabetes-induced hyperglycemia, inflammation and oxidative stress to ameliorate the reproductive function of diabetic male rats.

Keywords: Antrodia cinnamomea, diabetes mellitus, male reproduction, nanoparticles

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