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Glioblastoma multiforme (GBM) is one of the most aggressive brain and spinal cord tumors. Despite the significant development in application of antitumor drugs, no significant increases have been observed in the survival rates of patients with GBM, as GBM cells acquire resistance to conventional anticancer therapeutic agents. Multiple studies have revealed that PI3K/Akt, MAPK, Nanog, STAT 3, and Wnt signaling pathways are involved in GBM progression and invasion. Besides, biological processes such as anti-apoptosis, autophagy, angiogenesis, and stemness promote GBM malignancy. Resveratrol (RESV) is a non-flavonoid polyphenol with high antitumor activity, the potential of which, regulating signaling pathways involved in cancer malignancy, have been demonstrated by many studies. Herein, we present the potential of RESV in both single and combination therapy- targeting various signaling pathways- which induce apoptotic cell death, re-sensitize cancer cells to radiotherapy, and induce chemo-sensitizing effects to eventually inhibit GBM progression., Competing Interests: Declaration of Competing Interest The authors declare no conflict of interests., (Copyright © 2023 Elsevier GmbH. All rights reserved.)

Osimertinib sensitive and resistant NSCLC NCI-H1975 clones are used to model osimertinib acquired resistance in humanized and non-humanized mice and delineate potential resistance mechanisms. No new EGFR mutations or loss of the EGFR T790M mutation are found in resistant clones. Resistant tumors grown under continuous osimertinib pressure both in humanized and non-humanized mice show aggressive tumor regrowth which is significantly less sensitive to osimertinib as compared with parental tumors. 3-phosphoinositide-dependent kinase 1 (PDK1) is identified as a potential driver of osimertinib acquired resistance, and its selective inhibition by BX795 and CRISPR gene knock out, sensitizes resistant clones. In-vivo inhibition of PDK1 enhances the osimertinib sensitivity against osimertinib resistant xenograft and a patient derived xenograft (PDX) tumors. PDK1 knock-out dysregulates PI3K/Akt/mTOR signaling, promotes cell cycle arrest at the G1 phase. Yes-associated protein (YAP) and active-YAP are upregulated in resistant tumors, and PDK1 knock-out inhibits nuclear translocation of YAP. Higher expression of PDK1 and an association between PDK1 and YAP are found in patients with progressive disease following osimertinib treatment. PDK1 is a central upstream regulator of two critical drug resistance pathways: PI3K/AKT/mTOR and YAP., (© 2023. The Author(s).)

The rate of infertility has globally increased in recent years for a variety of reasons. One of the main causes of infertility in men is azoospermia that is defined by the absence of sperm in the ejaculate and classified into two categories: obstructive azoospermia and non-obstructive azoospermia. In non-obstructive azoospermia, genital ducts are not obstructed, but the testicles do not produce sperm at all, due to various reasons. Non-obstructive azoospermia in most cases has no therapeutic options other than assisted reproductive techniques, which in most cases require sperm donors. Here we discuss cell-based therapy approaches to restore fertility in men with non-obstructive azoospermia including cell-based therapies of non-obstructive azoospermia using regenerative medicine and cell-based therapies of non-obstructive azoospermia by paracrine and anti-inflammatory pathway, technical and ethical challenges for using different cell sources and alternative options will be described, and then the more effectual approaches will be mentioned as future trends., (© 2022. The Author(s), under exclusive licence to Society for Reproductive Investigation.)

This paper reports on developing a low cost but efficient paired emitter-detector diode (PEDD)-based photometer. The photometer consists of a white light-emitting diode (LED) as the emitter diode, an RGB LED as the detector diode, and a multimeter for recoding the signal. The developed PEDD-based photometer was utilized for the determination of liquid bleach adulteration in cow milk samples. N,N-Diethyl-p-phenylenediamine sulfate aqueous solution of pH 6 was used as a probe to monitor the presence of residual active chlorine in milk. The results showed that the developed method could be used to determine sodium hypochlorite in the concentration range of 0.5 to 20.0 ppm Cl 2 with 0.14 and 0.46 ppm Cl 2 limit of detection and limit of quantification, respectively. The intraday and interday precisions of the method at two concentration levels of 5.5 and 13.7 ppm Cl 2 were 1.04% and 0.52%, and 1.81% and 1.02%, respectively. The recoveries of 114.2% and 106.9% were obtained for 5.5 and 13.7 ppm Cl 2 concentrations levels, respectively. Real sample analyzes results showed that "maybe" liquid bleach adulteration in milk is the case for local distributors of raw milk., (© 2023. The Author(s).)

Resistance of bacterial pathogens to conventional antibiotics has remained a significant challenge in managing post-wound infections, especially in developing countries. Here, a nanofibrous chitosan/poly (vinyl alcohol) (CS/PVA) mat was designed for controlled delivery of three different concentrations of two antibiotics (colistin/meropenem ratio of 32/64 μg/ml (AB1), 64/128 μg/ml (AB2), and 128/256 (AB3) μg/ml) with synergistic antibacterial activity against ATCC and extensively drug-resistant (XDR) Acinetobacter baumannii clinical isolates. The scaffolds showed a uniform fibrous structure with no bead formation with a sustained release of the antibiotics for one week. The elongation at break, wettability, porosity, and average fiber diameter decreased with increased antibiotics concentrations. Young's modulus and tensile strength showed a significant increase after adding antibiotics. All the constructs showed excellent in vitro cytocompatibility for fibroblasts and biocompatibility in an animal model. The antibacterial assays confirmed the dose-dependent antibacterial activity of the CS/PVA. The scaffolds loaded with AB2 and AB3 showed biocidal properties against ATCC, while only CS/PVA/AB3 had antibacterial activity against XDR clinical isolates. This study suggests the CS/PVA/AB3 nanofibrous scaffold contained 128/256 μg/ml colistin/meropenem as an excellent antibacterial wound dressing for protection of skin wounds from XDR clinical isolates and now promises to proceed with pre-clinical investigations., Competing Interests: Declaration of competing interest The authors declare no conflict of interest., (Copyright © 2022. Published by Elsevier B.V.)

Background: Obsessive-compulsive disorder (OCD) is a common psychiatric disorder. The Food and Drug Administration (FDA) approved repetitive transcranial magnetic stimulation (rTMS) to treat OCD in 2018. So far, various approaches to treat this disorder have been evaluated. We evaluated the effect of adjunctive low-frequency rtMS over the left dorsolateral prefrontal cortex in patients with OCD refractory to treatment., Methods: The present clinical trial was done on 37 patients with OCD referring from the psychiatry clinic, 22 Bahman Hospital, Qazvin province, between 2018 and 2020 and patients were randomly divided into two groups. The intervention group received rTMS treatment at 1 Hz for 20 min (1200 pulses/day) over the left DLPFC area as adjunctive to the medical treatment three times a week and for five weeks, whereas those in the control group were subjected to only the sham condition plus their medical treatment. The Yale-Brown Obsessive-Compulsive Scale (Y-BOC.S) was completed by patients before the study, following sessions 5 and 10 during the intervention, at the end of the intervention, and three to six months after the intervention under the direct supervision of a psychiatrist. SPSS software version 26 was used to compare the results between the two groups., Results: The intervention group showed significantly lower mean Y-BOCS scores after the intervention and at follow-up (P < 0.05) and all patients of the intervention group showed significantly lower Y-BOCS scores than their own baseline scores (P < 0.05). Also, using antipsychotic agents along with the serotonergic agents yielded significantly lower scores in the intervention group at the end of the intervention (P < 0.05). All the patients were found with higher follow-up scores than their scores at the end of the intervention; however, this difference was not significant (p > 0.05)., Conclusion: Adjunctive low-frequency (1 Hz) rTMS over the left DLPFC is able to effectively reduce Y-BOCS score in OCD patients refractory to treatment following 15 sessions, and the reduction was durable even after three to six months. Using antipsychotic agents as an adjuvant with serotonergic agents was identified as a possible predictor for response to adjunctive rTMS therapy., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Attempts are being made to develop an ideal wound dressing with excellent biomechanical and biological properties. Here, a thermos-responsive hydrogel is fabricated using chitosan (CTS) with various concentrations (1%, 2.5%, and 5% w/v) of solubilized placental extracellular matrix (ECM) and 20% β-glycerophosphate to optimize a smart wound dressing hydrogel with improved biological behavior. The thermo-responsive CTS (TCTS) alone or loaded with ECMs (ECM-TCTS) demonstrate uniform morphology using SEM. TCTS and ECM1%-TCTS and ECM2.5%-TCTS show a gelation time of 5 min at 37 °C, while no gel formation is observed at 4 and 25 °C. ECM5%-TCTS forms gel at both 25 and 37 °C. The degradation and swelling ratios increase as the ECM content of the hydrogel increase. All the constructs show excellent biocompatibility in vitro and in vivo, however, the hydrogels with a higher concentration of ECM demonstrate better cell adhesion for fibroblast cells and induce expression of angiogenic factors (VEGF and VEGFR) from HUVEC. Only the ECM5%-TCTS has antibacterial activity against Acinetobacter baumannii ATCC 19606. The data obtained from the current study suggest the ECM2.5%-TCTS as an optimized smart biomimetic wound dressing with improved angiogenic properties now promises to proceed with pre-clinical and clinical investigations., (© 2022 Wiley-VCH GmbH.)

Background: Lower abdominal or pelvic pain is a common complaint among women and one of the most challenging findings to evaluate. We performed the present study to construct a new algorithm for predicting the chance of ovarian torsion among women with acute lower abdominal pain. Methods: This diagnostic retrospective cross-sectional study was performed on all female individuals who were referred to Imam Hossein Medical Center, Tehran, Iran, with the chief complaint of acute lower abdominal pain, and underwent laparotomy between 2010 and 2016. Clinical and paraclinical findings were evaluated to construct a predictive model for ovarian torsion. The variables were compared in 2 groups. The first group included individuals with a final diagnosis of ovarian torsion and the second group included those individuals with any diagnosis other than ovarian torsion. All data were compared between these 2 groups using SPSS software Version 21 to find the related findings with a predictive value for ovarian torsion. Results: A total of 372 participants were evaluated, of whom 116 participants (31.2%) had ovarian torsion (case group) and 256 participants had other diagnoses for their lower abdominal pain (control group). Nausea and vomiting ( p < 0.001), tenderness ( p < 0.001), the size of ovarian mass ( p = 0.004), and the percentage of polymorphonuclear ( p < 0.001) showed significant relationships with ovarian torsion as the final diagnosis. Multiple logistic regression models were constructed to predict the factors affecting ovarian torsion, and a scoring system was designed to predict ovarian torsion, with a sensitivity of 77.59% (68.9%- 84.8%) and specificity of 74.61% (68.8% 79.8%). Conclusion: The proposed model is suitable for predicting ovarian torsion and its necessary information is readily available from individuals' history, examination findings, laboratory results, and an ultrasound exam., (© 2022 Iran University of Medical Sciences.)

Some mineral elements exert beneficial neuroprotection, especially in the form of nanoparticles. The aim of the present study was to evaluate the effects of selenium nanoparticles (SeNPs) and polyvinyl alcohol (PVA)-coated SeNPs (PVA-SeNPs) on Alzheimer's disease (AD) in a rat model of AD. Twenty-eight rats were randomly divided into four groups of seven rats: control, Alz, Alz + Se, and Alz + Se-PV groups. PVA-SeNPs and SeNPs were chemically synthesized and orally administrated (0.4 mg/kg) to the AD rats for one month. AD was induced by an intracerebroventricular (ICV) injection of streptozotocin (STZ). The memory function was assessed by the novel object recognition (NOR) and passive avoidance learning (PAL) tests. The expression of hippocampal brain-derived neurotrophic factor (BDNF) and stress oxidative markers (MDA and TAC), and the number of amyloid-beta (Aβ) plaques were assessed using ELISA kits, biochemical methods, and Congo red staining, respectively. The results of the behavioral tests showed that the discrimination index in the NOR test increased in the Alz + PVA-SeNPs group compared to the Alz group. Memory performance in the PAL task improved in the PVA-SeNPs and SeNPs groups compared to the Alz group. The level of the BDNF in both of the Alz treatment groups (PVA-SeNPs and SeNPs) showed a significant increase compared to the Alz group. MDA levels and Aβ plaques decreased in both NPs-treated Alz groups, while TAC levels decreased in all Alz groups. PVA-SeNPs were more effective than SeNPs in the improvement of the cognition deficit. The results suggest that PVA-SeNPs improve the cognition and memory deficit induced by an ICV injection of STZ through a decrease in the number of Aβ plaques and malondialdehyde levels and an increase in the BDNF levels., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

Amyotrophic lateral sclerosis (ALS) is a genetically and phenotypically heterogeneous disease results in the loss of motor neurons. Mounting information points to involvement of other systems including cognitive impairment. However, neither the valid biomarker for diagnosis nor effective therapeutic intervention is available for ALS. The present study is aimed at identifying potentially genetic biomarker that improves the diagnosis and treatment of ALS patients based on the data of the Gene Expression Omnibus. We retrieved datasets and conducted a weighted gene co-expression network analysis (WGCNA) to identify ALS-related co-expression genes. Functional enrichment analysis was performed to determine the features and pathways of the main modules. We then constructed an ALS-related model using the least absolute shrinkage and selection operator (LASSO) regression analysis and verified the model by the receiver operating characteristic (ROC) curve. Besides we screened the non-preserved gene modules in FTD and ALS-mimic disorders to distinct ALS-related genes from disorders with overlapping genes and features. Altogether, 4198 common genes between datasets with the most variation were analyzed and 16 distinct modules were identified through WGCNA. Blue module had the most correlation with ALS and functionally enriched in pathways of neurodegeneration-multiple diseases', 'amyotrophic lateral sclerosis', and 'endocytosis' KEGG terms. Further, some of other modules related to ALS were enriched in 'autophagy' and 'amyotrophic lateral sclerosis'. The 30 top of hub genes were recruited to a LASSO regression model and 5 genes (BCLAF1, GNA13, ARL6IP5, ARGLU1, and YPEL5) were identified as potentially diagnostic ALS biomarkers with validating of the ROC curve and AUC value., (© 2022. The Author(s).)

In this study, polyvinyl alcohol hydrogel chains were crosslinked by polyurethane in order to synthesize a suitable substrate for cartilage lesions. The substrate was fully characterized, and in vitro and in vivo investigations were conducted based on a sheep model. In vitro tests were performed based on the chondrocyte cells with the Alcian Blue and safranin O staining in order to prove the presence of proteoglycan on the surface of the synthesized substrate, which has been secreted by cultures of chondrocytes. Furthermore, the expression of collagen type I, collagen type II, aggrecan, and Sox9 was presented in the chondrocyte cultures on the synthesized substrate through RT-PCR. In addition, the H&E analysis and other related tests demonstrated the formation of neocartilage tissue in a sheep model. The results were found to be promising for cartilage tissue engineering and verified that the isolated chondrocyte cultures on the synthesized substrate retain their original composition., (© 2022 Wiley Periodicals LLC.)

In recent years, novel strategies to control insects have been based on protease inhibitors (PIs). In this regard, molecular docking and molecular dynamics simulations have been extensively used to investigate insect gut proteases and the interactions of PIs for the development of resistance against insects. We, herein, report an in silico study of (disodium 5'-inosinate and petunidin 3-glucoside), (calcium 5'-guanylate and chlorogenic acid), chlorogenic acid alone, (kaempferol-3,7-di-O-glucoside with hyperoside and delphinidin 3-glucoside), and (myricetin 3'-glucoside and hyperoside) as potential inhibitors of acetylcholinesterase receptors, actin, α-tubulin, arginine kinase, and histone receptor III subtypes, respectively. The study demonstrated that the inhibitors are capable of forming stable complexes with the corresponding proteins while also showing great potential for inhibitory activity in the proposed protein-inhibitor combinations.

Background: Electromagnetic waves can cause biological effects on repair process. Due to the proximity of the jawbone and the soft tissue around it in a part of the face with which it has the closest contact during the cell phone use, this study aims to investigate the effect of mobile waves on socket healing after tooth extraction in rats., Methods: This experimental study was conducted on 32 rats. The case group was exposed to a 900 MHz frequency electromagnetic field for 30 min/d. Sacrificed eight rats from the case group and 7 rats from the control group on day 14, and 8 rats from the case group and 7 rats from the control group were sacrificed on day 28 at the end of the radiation period and CBCT and microscopic examinations on the maxillary bones and soft tissue were performed., Results: According to the findings, the healing process was significantly different in two groups in terms of the percentage of new bone formation on day 14 after the end of radiation (P=0.014). The other measured parameters including the degree of inflammation, thickness of the formed bone, number of osteoblasts and Gray Scale had no significant difference between the two groups in any of the 14-day and 28-day intervals., Conclusions: The results of this study showed that intermittent exposure to high frequency electromagnetic fields over a period of 20 hours has no significant effect on the healing process of alveolar socket after tooth extraction in rats.

Although there are various studies attempted to clarify the genetic mechanism of plant response to drought stress that reduces crop yield, a meta-analysis can integrate the results of them to provide a better picture of the issue. Therefore, in this study, several microarray datasets of rice were meta-analysed under drought stress and normal condition using the R packages. Accordingly, differentially expressed genes (meta-DEGs) were identified. The results showed 643 and 677 upregulated and downregulated genes, respectively. The significant common Gene Ontology (GO) terms between the up- and downregulated genes were responses to abiotic stimulus , water deprivation , oxygen-containing compound and abscisic acid . The transcription factors (TF) survey showed that bHLH under drought stress activates up genes 42% more than down genes while bzip Homeodomain activates down genes 54% more than up genes. The hub downregulated genes obtained from this study were mainly related to photosynthesis and the hub upregulated genes were mainly related to stress tolerance which include heat shock proteins (HSPs), late embryogenesis abundant (LEAs), calmodulin-like protein (CML), phosphatase 2C (PP2Cs) and IAA genes. Moreover, this meta-analysis data were compared with other experimental data and the results confirmed the up and down expression of them. Our findings can provide novel insights into the molecular mechanism of rice (Oryza sativa L.) response to drought stress.

Background: Glioblastoma (GBM) is the most common primary central nervous system malignancy with a low survival without extra logistics. Currently, there is no definitive chemotherapy among the studied options. This study aims to evaluate the neuroprotective effects of dimethyl fumarate (DMF) on surgical brain injuries in patients treated for GBM. Materials and Methods: This randomized, phase II, placebo, triple-blinded, controlled trial was performed on 36 patients with a diagnosis of GBM. All the patients received DMF (240 mg, three-times per day) or placebo (with the same shape and administration route) one week before surgery. Also, patients in both groups after the operation received standard treatments (radiotherapy plus chemotherapy). In addition, Kanofsky's performance status (KPS) score was evaluated at baseline and one month later. Also, serum S100β was measured 48 hours before and after surgery. Results: There was no significant difference among DMF and control groups with regard to age, gender, and the extent of resections (P˃0.05). The most adverse event in both groups was a headache. Although the serum S100β level was not markedly changed after surgery, the mean KPS in the DMF group was higher than in the control group after surgery. Conclusion: The DMF could be a possible good regime for the treatment of GBM; however, questions are raised regarding its efficacy and application for the addition to standard treatment., (Copyright© 2021, Galen Medical Journal.)

Clustered regularly interspaced short palindromic repeats (CRISPR) together with their CRISPR-associated (Cas) genes are widely distributed in prokaryotes that provide an adaptive defense mechanism against foreign invasive DNA. There is relatively little knowledge about the CRISPR-Cas diversity and evolution in Lactobacillus brevis strains. Therefore, in this study, a genome-mining approach was employed to investigate the diversity and occurrence of the CRISPR-Cas system in 83 L. brevis strains. Moreover, trans-activating CRISPR RNA (tracrRNA) and protospacer adjacent motif (PAM) as pivotal elements for the successful targeting and inference of phages by the subtype II CRISPR-Cas systems were surveyed. Finally, evolutionary paths of L. brevis strains under selective pressure from foreign invasive DNA such as plasmids and phages of studied strains were surveyed using acquisition and deletion events analysis of spacers. A total of 127 confirmed CRISPRs were identified, which were distributed in 69 strains. Among strains with confirmed CRISPRs, 35 strains only contained one CRISPR locus, 23 strains contained two CRISPR loci, and 12 strains contained three to six CRISPR loci. L. brevis strains frequently harbor more than one CRISPR system. Analysis of confirmed CRISPR arrays showed that 31 out of 127 confirmed CRISPRs included Cas genes which were categorized as one of the II-A, II-C, and I-E subtypes. Analysis of subtype II-A spacers reflected divergent evolution for 18 strains into 16 unique groups. Additional analysis of spacer sequences also confirmed the implication of characterizing CRISPR-Cas systems in targeting of phages and plasmids. The current study highlighted the potential of utilizing CRISPR spacer polymorphism in genotyping lactobacillus strains. Moreover, it provides deep insights into the occurrence, diversity, and functional impacts of the CRISPR-Cas system in L. brevis strains., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2022 Panahi, Majidi and Hejazi.)

KRAS/LKB1 (STK11) NSCLC metastatic tumors are intrinsically resistant to anti-PD-1 or PD-L1 immunotherapy. In this study, we use a humanized mouse model to show that while carboplatin plus pembrolizumab reduce tumor growth moderately and transiently, the addition of the tumor suppressor gene TUSC2, delivered systemically in nanovesicles, to this combination, eradicates tumors in the majority of animals. Immunoprofiling of the tumor microenvironment shows the addition of TUSC2 mediates: (a) significant infiltration of reconstituted human functional cytotoxic T cells, natural killer cells, and dendritic cells; (b) induction of antigen-specific T cell responses; (c) enrichment of functional central and memory effector T cells; and (d) decreased levels of PD-1 + T cells, myeloid-derived suppressor cells, Tregs, and M2 tumor associated macrophages. Depletion studies show the presence of functional central and memory effector T cells are required for the efficacy. TUSC2 sensitizes KRAS/LKB1 tumors to carboplatin plus pembrolizumab through modulation of the immune contexture towards a pro-immune tumor microenvironment., (© 2022. The Author(s).)

The use of herbal medicine has considerably grown worldwide in the past two decades. Studies have shown that the prevalence of herbal diet therapy in pregnancy ranged from 1% to 60% in different societies. Many clinical reports have shown that some herbal medicines may have toxic effects on pregnant women and their fetuses because active ingredients of some medicinal plants can readily pass through the biological barriers (e.g., placental barrier). In the present study, we aimed to systematically review the literature to discover potential benefits versus the hazards of herbal therapy during pregnancy. For this purpose, a comprehensive literature review was performed, and after the literature search and selection of the appropriate documents, the desired data were extracted and reported. From 35 articles with a total of 39,950 study population, the results showed that some medicinal plants could cause severe toxicity on mothers and fetuses, in addition to abortion during pregnancy. It was also shown that some plants may lead to developmental abnormalities or fetal death. Findings of this survey showed that some herbal medicines have toxic, teratogenic, and abortive potential, particularly in the first trimester of pregnancy because active ingredients of some medicinal plants are able to pass through the placental barrier and reach the fetus., (© 2022 John Wiley & Sons Ltd.)

Objective: Infection with human tumor viruses is one of the hypothesized causes of cancer. The current investigation aimed to explore the presence and quantitative analysis of a new human tumor virus, Merkel cell polyomavirus (MCPyV) in tissue samples of 114 patients with oral cavity lesions including oral squamous cell carcinoma (OSCC), oral lichen planus (OLP), Dysplasia and oral irritation fibroma (OIF) in Northern Iran., Methods: From 114 formalin fixed paraffin embedded samples; 35 with SCC, 29 with OLP, 14 with dysplasia and 36 with OIF were cut, deparaffinized and DNA was extracted. Quantitative detection of MCPyV large T antigen was performed by absolute quantitative Real-Time PCR., Result: MCPyV DNA was detected in 30.6% (n: 11/36) of IF, 24.1% (n; 7/29) of OLP, 21.4% (n:3/14) of dysplasia and 20% (n;7/35) of OSCC samples. The mean MCPyV DNA copy number was 2.32×10-2 ± 3.97 ×10-2, 2.02×10-2 (SD=3.13×10-2), 2.69×10-4 (SD=2.51×10-4), and 2.56×10-4 (SD=6.73×10-4) per cell in OSCC, dysplasia and both of OLP and OIF samples, respectively (P=0.76)., Conclusion: This study provides the first data from Iran regarding the presence of MCPyV genome in oral cavity lesions and oral cancer. These results also emphasize that MCPyV has an active role in the occurrence of oral lesions and progression to cancer. Further studies should be carried out to clarify the role of MCPyV in oral cavity lesions.

Chitosan and its derivatives have been widely used as the adsorbents for different types of water pollutants. This review paper lists various physically and chemically modified chitosan-based adsorbents such as chitosan beads, cross-linked chitosan, chitosan-polymer composites, chitosan-inorganic material composites, and chitosan-metal complexes for the removal of nitrogen-containing pollutants (nitrate, nitrite, ammonia, and ammonium ions) from aqueous solutions. It covers preparation strategies, the effect of modification on adsorbent structure, and the impact of adsorption variables using batch and fixed-bed column studies. In addition to demonstrating the applications of chitosan and its derivatives in the removal of nitrogenous pollutants from water, it helps researchers understand the influence of modification of chitosan on its adsorption capacity as well as physical and chemical properties., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Electronic correlations play important roles in driving exotic phenomena in condensed matter physics. They determine low-energy properties through high-energy bands well-beyond optics. Great effort has been made to understand low-energy excitations such as low-energy excitons in transition metal dichalcogenides (TMDCs), however their high-energy bands and interlayer correlation remain mysteries. Herewith, by measuring temperature- and polarization-dependent complex dielectric and loss functions of bulk molybdenum disulphide from near-infrared to soft X-ray, supported with theoretical calculations, we discover unconventional soft X-ray correlated-plasmons with low-loss, and electronic transitions that reduce dimensionality and increase correlations, accompanied with significantly modified low-energy excitons. At room temperature, interlayer electronic correlations, together with the intralayer correlations in the c-axis, are surprisingly strong, yielding a three-dimensional-like system. Upon cooling, wide-range spectral-weight transfer occurs across a few tens of eV and in-plane p-d hybridizations become enhanced, revealing strong Coulomb correlations and electronic anisotropy, yielding a two-dimensional-like system. Our result shows the importance of strong electronic, interlayer and intralayer correlations in determining electronic structure and opens up applications of utilizing TMDCs on plasmonic nanolithrography., (© 2021. The Author(s).)

Acute respiratory distress syndrome (ARDS) is the most common cause of death in COVID-19 patients. The cytokine storm is the main driver of the severity and magnitude of ARDS. Placenta-derived decidua stromal cells (DSCs) have a stronger immunosuppressive effect than other sources of mesenchymal stromal cells. Safety and efficacy study included 10 patients with a median age of 50 (range 14-68) years with COVID-19-induced ARDS. DSCs were administered 1-2 times at a dose of 1 × 10 6 /kg. End points were safety and efficacy by survival, oxygenation and effects on levels of cytokines. Oxygenation levels increased from a median of 80.5% (range 69-88) to 95% (range 78-99) (p = 0.012), and pulmonary infiltrates disappeared in all patients. Levels of IL-6 decreased from a median of 69.3 (range 35.0-253.4) to 11 (range 4.0-38.3) pg/ml (p = 0.018), and CRP decreased from 69 (range 5-169) to 6 (range 2-31) mg/ml (p = 0.028). Two patients died, one of a myocardial infarction and the other of multiple organ failure, diagnosed before the DSC therapy. The other patients recovered and left the intensive care unit (ICU) within a median of 6 (range 3-12) days. DSC therapy is safe and capable of improving oxygenation, decreasing inflammatory cytokine level and clearing pulmonary infiltrates in patients with COVID-19., (© 2021 The Authors. Journal of Cellular and Molecular Medicine published by Foundation for Cellular and Molecular Medicine and John Wiley & Sons Ltd.)

Breast cancer is the most common cancer among women in terms of prevalence and mortality, and chemotherapy is one of the most effective treatments at higher stages. However, resistance to chemotherapy is the main obstacle in the treatment of this cancer. Accumulated evidence identified the PD-L1 protein as an essential protein in the development of different cancers. Abnormal expression of this protein in various tumor cells is linked to cancer development and inhibiting the function of immune cells, which correlated with reduced beneficial effects of chemotherapy drugs. In the present study, the effects of common chemotherapy drugs including doxorubicin, paclitaxel, and docetaxel on the expression of the PD-L1 gene were investigated by qRT-PCR before and after the treatment with these drugs in MD231, MD468, SKBR3 breast cancer cell lines. Also, the MTT test was applied to examine the effects of drugs on the growth and proliferation of cancer cells considering PD-L1 expression. The expression of the PD-L1 gene increased after 24 and 48 h of treatment with chemotherapy drugs. The obtained results indicate the enhancing effects of chemotherapy drugs on PD-L1 gene expression, which have a suppressive effect on the immune system against breast cancer. The use of these drugs as the first line of chemotherapy in triple-negative breast cancer is not recommended. However, there is still a need for further experimental and clinical research on the exact effects of these drugs on undesired immune cells exhaustion in breast cancer therapy., (© 2021. Springer Science+Business Media, LLC, part of Springer Nature.)

Background: Rheumatoid arthritis (RA) is a systemic chronic disease with synovial membrane, tendon and articular tissue inflammation. Current treatments of RA have many side effects and are quite expensive. Today, new treatments procedures and inexpensive herbal drugs are developed. Marham-Mafasel is mainly made out of two traditional herbs (Arnebia euchroma and Martricaria chamomilla)., Objective: In this study, for the first time, the impact of Marham-Mafasel on joint inflammation, histopathological changes and IL-1β gene expression was evaluated in RA animal model., Methods: The RA was induced by a single s.c. injection of 0.1 ml Freund's complete adjuvant into the left hind footpad. In continuous, 15 RA male Wistar rats were used in three groups: I: Control; II: Treatment I (Piroxicam) and III: Treatment II (Marham-Mafasel). The volume of the hind paw was measured every day from 0 to 19 using water changed volume approach. The inflammation in the joint was evaluated using histopathology assay and gene expression of IL-1β was evaluated with use of Real-Time PCR., Results: Hind paw swelling of Marham-Mafasel at days 10th and 19th was reduced compared with the control group (p < 0.05). There was no statistically difference in histological degrading and changes index in three groups (p ≥ 0.05). Relative expression of IL-1β in Marham-Mafasel group was significantly decreased compared with other groups., Conclusion: The co-administration of M. Chamomile and A. euchroma, called Marham-Mafasel, decreases IL-1β gene expression that leads to a reduction in inflammation in rheumatoid arthritis (RA) animal model., (© 2021 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Despite all the advances in the production of transgenic mice, the production efficiency of these animal models is still low. Given that the expression of developmental genes has a critical role in growth and development of embryo, we determined the expression pattern of pluripotency, trophectoderm and imprinting genes in the Rag1 (recombination-activating gene 1) knocked-out blastocysts resulting from microinjection of CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) constructs into the zygote cytoplasm of C57bl6 mice. Following microinjection, the embryos were cultured and the gene expression of developed blastocysts and natural blastocysts (Sham and control groups) were evaluated using real-time PCR. The agarose gel to confirm the deletion in the Rag1 gene in Rag1 knocked-out blastocyst. Our results showed that the expression of trophectoderm genes (-TEAD-4 and Cdx2), pluripotency genes (Nanog and Oct-4) and imprinting gene (H19) in the Rag1 knocked-out group was significantly lower compared with the embryos obtained from Natural fertilization. According to these findings, manipulation, embryo culture and microinjection of CRISPR constructs into the zygote cytoplasm of mice led to reduced expression of imprinting, pluripotency and trophectoderm genes. Therefore, the Rag1 knocked-out embryos produced by the CRISPR/Cas9 system are of low quality, which reduces the chances of live birth in these animals and may cause various abnormalities in fetuses., (© 2021 The Authors Veterinary Medicine and Science Published by John Wiley & Sons Ltd.)

Aims: Memory impairment is determined to be the most well-known symptom of Alzheimer's disease (AD). Although cell therapy seems is an efficient therapeutic strategy to attenuate the AD-related memory impairment, transplanted cells have a short lifespan and do not survive long term in the recipient animals. Herein, we investigated whether the combination therapy of Selenium nanoparticles (SeNPs) and stem cells attenuates the neurotoxicity in an AD animal model., Material and Methods: The adipose-derived mesenchymal stem cells (AMSCs) were transplanted in the AD model. In addition to cell injections, the animals also received oral administration of SeNPs (0.4 mg/kg) for one month. Recognition memory, cell survival, and BDNF concentration were assessed using the novel object recognition task, immunofluorescence, and ELISA methods., Key Findings: Our results showed that the combined therapy was more effective in increasing the discrimination index than the administering SeNPs or AMSCs alone. Moreover, SeNPs and stem cells together had the greatest effects in reducing the deposition of Aβ and increasing the concentration of BDNF. Ultimately, the survival and proliferation of transplanted cells were more in the group that received stem cells besides SeNPs., Significance: Taken together, it seems that the transplantation of MSCs combined with SeNPs could achieve better results in the neuroprotection in the AD model than a conventional treatment of SeNPs or stem cells alone., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Ischemic heart disease (IHD) is known as the leading cause of death in both genders. Moreover, significant sex differences were found in cardiac structure, function, pathophysiology, presentation, treatment, and outcome of IHD. The presence of unique risk factors such as exposure to menarche and pregnancy, more anemia, hypertension, and autoimmune disorders in women have recently received attention. Ischemic symptoms are more indefinite and vague in women compared to men as well as a delay in diagnosis, treatment, and worse outcomes compared to men. Women usually receive less evidence-based treatment and intervention, with less concern on preventive health care. Clinical trials primarily recruit male patients and women are underrepresented. Without any correct diagnosis, treatment, and prevention, these problems are accumulated and continue up to older age. Accordingly, with the belief of longer life in women and the increased prevalence of IHD with aging, it will become an important public health problem and concern in the future. This narrative review aimed to provide an overview of some of the differences between the two genders in terms of IHD with paying more attention to practical points., (Copyright and License information: Journal of Geriatric Cardiology 2021.)

Background: Little information is available on the application of marker-trait association (MTA) analysis for traits related to drought tolerance in smooth bromegrass. The objectives of this study were to identify marker loci associated with important agronomic traits and drought tolerance indices as well as fining stable associations in a diverse panel of polycross derived genotypes of smooth bromegrass. Phenotypic evaluations were performed at two irrigation regimes (normal and deficit irrigation) during 2 years; and association analysis was done with 626 SRAP markers., Results: The results of population structure analysis identified three main subpopulations possessing significant genetic differences. Under normal irrigation, 68 and 57 marker-trait associations were identified using general linear model (GLM) and mixed linear mode1 (MLM), respectively. While under deficit irrigation, 61 and 54 markers were associated with the genes controlling the studied traits, based on these two models, respectively. Some of the markers were associated with more than one trait. It was revealed that markers Me1/Em5-11, Me1/Em3-15, and Me5/Em4-7 were consistently linked with drought-tolerance indices., Conclusion: Following marker validation, the MTAs reported in this panel could be useful tools to initiate marker-assisted selection (MAS) and targeted trait introgression of smooth bromegrass under normal and deficit irrigation regimes, and possibly fine mapping and cloning of the underlying genes and QTLs.

The use of peptide-drug conjugates has generated wide interest as targeted antitumor therapeutics. The anthracycline antibiotic, daunomycin, is a widely used anticancer agent and it is often conjugated to different tumor homing peptides. However, comprehensive analytical characterization of these conjugates via tandem mass spectrometry (MS/MS) is challenging due to the lability of the O-glycosidic bond and the appearance of MS/MS fragment ions with little structural information. Therefore, we aimed to investigate the optimal fragmentation conditions that suppress the prevalent dissociation of the anthracycline drug and provide good sequence coverage. In this study, we comprehensively compared the performance of common fragmentation techniques, such as higher energy collisional dissociation (HCD), electron transfer dissociation (ETD), electron-transfer higher energy collisional dissociation (EThcD) and matrix-assisted laser desorption/ionization-tandem time-of-flight (MALDI-TOF/TOF) activation methods for the structural identification of synthetic daunomycin-peptide conjugates by high-resolution tandem mass spectrometry. Our results showed that peptide backbone fragmentation was inhibited by applying electron-based dissociation methods to conjugates, most possibly due to the "electron predator" effect of the daunomycin. We found that efficient HCD fragmentation was largely influenced by several factors, such as amino acid sequences, charge states and HCD energy. High energy HCD and MALDI-TOF/TOF combined with collision induced dissociation (CID) mode are the methods of choice to unambiguously assign the sequence, localize different conjugation sites and differentiate conjugate isomers.

Separating cells from the body and cultivating them in vitro will alter the function of cells. Therefore, for optimal cell culture in the laboratory, conditions similar to those of their natural growth should be provided. In previous studies, it has been shown that the use of cellular shape at the culture surface can regulate cellular function. In this work, the efficiency of the imprinting method increased by using microfluidic chip design and fabrication. In this method, first, a cell-imprinted substrate of chondrocytes was made using a microfluidic chip. Afterwards, stem cells were cultured on a cell-imprinted substrate using a second microfluidic chip aligned with the substrate. Therefore, stem cells were precisely placed on the chondrocyte patterns on the substrate and their fibroblast-like morphology was changed to chondrocyte's spherical morphology after 14-days culture in the chip without using any chemical growth factor. After chondrogenic differentiation and in vitro assessments (real-time PCR and immunocytotoxicity), differentiated stem cells were transferred on a collagen-hyaluronic acid scaffold and transplanted in articular cartilage defect of the rabbit. After 6 months, the post-transplantation analysis showed that the articular cartilage defect had been successfully regenerated in differentiated stem cell groups in comparison with the controls. In conclusion, this study showed the potency of the imprinting method for inducing chondrogenicity in stem cells, which can be used in clinical trials due to the safety of the procedure., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Recent investigations are seeking a novel treatment to control the new pandemic of coronavirus 19 (COVID-19). The aim of this systematic review was to study the effect of ozone therapy on COVID-19 patients and the available supporting evidence. Electronic databases including MEDLINE (via PubMed), EMBASE, Cochrane Library (CENTRAL), and TRIP, clinical trial registries, and preprint sources were searched for published evidence-based articles. In addition, manual searching was conducted for articles published up to April 6, 2020, using MeSH and free text keywords with no language limitation. Articles were screened, categorized, and extracted for relative data. Data were reported in a descriptive manner. Among 234 articles, 9 were selected for review of the inclusion criteria. No published original articles were found regarding the efficacy of ozone therapy on COVID-19. Five review studies were found in which the potential role of systemic ozone therapy was concluded to be effective in controlling COVID-19 because of its antiviral, oxygenation, anti-inflammatory, oxidation balancing, and immunomodulation effects. Three ongoing clinical trials were registered in China. A preliminary report of an ongoing study in Italy on 46 patients (11 intubated and 35 non-intubated) showed that in 39 (84%) of the patients, an improvement was seen. In spite of the promising background data, as well as the expert opinions and a preliminary report indicating the effectiveness of ozone, there is still not enough evidence to confirm this as a viable treatment option for COVID-19., (© 2021. The Author(s), under exclusive license to Springer Nature Switzerland AG.)

The present study aims to evaluate the inhibitory effects of artesunate (a semi-synthetic derivative of artemisinin) on HSP70 and Bcl-2 expression in two breast cancer cell lines, 4T1 and MCF-7. In addition, to determine in vitro inhibitory effect of artesunate against the ATPase activity of purified recombinant HSP70, it was tested in a carbonic anhydrase refolding assay with purified HSP70. Our results demonstrated that the artesunate not only induced apoptosis but also lead to the inhibition of HSP70 ATPase activity the in vitro (P < 0.001). The extent of HSP70 refolding inhibition increased with increasing μM concentrations of artesunate. Incubation of HSP70 with 50 μM artesunate showed significant inhibition of refolding activity by 38%. The IC 50 values of artesunate for 4T1 cells, were lower than MCF-7 cells, indicating the higher sensitivity of the triple-negative phenotype. Furthermore, artesunate significantly down-regulated the expression of Bcl-2 and HSP70 while enhancing the expression of cleaved caspase-9 in MCF-7 and 4T1 cells. It also induced caspase-9 activity at 18 h in a dose-dependent manner in two breast cancer cell lines. Generally, our results show that the artesunate induces caspase-dependent apoptosis through the inhibition of HSP70 expression., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Currently, the efficient production of chimeric mice and their survival are still challenging. Recent researches have indicated that preimplantation embryo culture media and manipulation lead to abnormal methylation of histone in the H19/Igf2 promotor region and consequently alter their gene expression pattern. This investigation was designed to evaluate the relationship between the methylation state of histone H3 and H19/Igf2 expression in mice chimeric blastocysts., Methods: Mouse 129/Sv embryonic stem cells (mESCs) expressing the green fluorescent protein (mESCs-GFP) were injected into the perivitelline space of 2.5 days post-coitis (dpc) embryos (C57BL/6) using a micromanipulator. H3K4 and H3K9 methylation, and H19 and Igf2 expression was measured by immunocytochemistry and q-PCR, respectively, in blastocysts., Results: Histone H3 trimethylation in H3K4 and H3K9 in chimeric blastocysts was significantly less and greater, respectively (p< 0.05), than in controls. H19 expression was significantly less (p< 0.05), while Igf2 expression was less, but not significantly so, in chimeric than in control blastocysts., Conclusion: Our results showed, that the alteration ofH3K4me3 and H3K9me3 methylation, change H19/Igf2 expression in chimeric blastocysts.

Clinical toxicology is not recognized as a clinical speciality in Iran. After the chemical war gas attack by the Iraqi army against the Iranian troops in the 1980s, health professionals and Iranian authorities noticed the importance of this field in clinical medicine. Collaboration between the clinical toxicologists and toxicologists of pharmacy schools resulted in the establishment of the Iranian Society of Toxicology and Poisonings in 1991 and the National Board of Toxicology in 1993. Clinical toxicology fellowship was also formed as a joint collaboration between the toxicology and internal medicine boards in 2010. Medical doctors who specialized in clinical medicine are eligible to take the entrance examination of the fellowship. In spite of the advancement of clinical toxicology and increased number of acute poisonings and drug abuse, undergraduate teaching in this field is still lacking and being taught as part of the forensic medicine curriculum since 1952. There is a lack of an efficient national poison information and control centre (s) in Iran, and no action plan and practical efforts have been done for poisoning prevention. Therefore, the number of drug abuse and acute poisonings has increased over the past four decades and induced cultural, social and health problems. According to Iranian legal medicine organization reports, poisoning is the second-most occurring cause of unnatural death. The suicidal attempt is the most common method of acute poisoning in adults. Suicidal attempt including self-poisoning is not accepted in the Islamic point of view, and thus self-poisoning is mostly neglected and may not be treated appropriately in time in some regions of Iran. Accidental poisoning in children is also common in Iran and estimated to be between 20 000 and 25 000 cases annually over the recent years. In addition, social, cultural and economic problems have induced more health problems such as drug abuse and addiction even in children. Adulterated opium to lead for economic gaining has produced thousands of cases of lead poisoning over the past few years in nearly all opium addicts, which is still a major health problem in Iran. Ban on alcoholic beverages leads some people to make their own home-made spirits, which is unfortunately contaminated with methanol. Thousands of cases of methanol poisoning and even some epidemics have occurred over the past four decades in some parts of the country. Lack of availability of essential antidotes such as succimer and fomepizole has been a major problem for the effective treatment of poisoned patients. Despite the well-known fact that cases of poisoning and drug overdose constitute a significant proportion of hospital admissions in some developing countries, clinical toxicology education and medical care of the poisoned patients are lacking. Therefore, policymakers and health authorities should realize the importance of toxicology in clinical medicine. The Iranian Ministry of Health, medical care and Medical Education should implement clinical toxicology courses for medical students; establish effective national poisons information and control centres and advance clinical toxicology services for appropriate management of poisoned patients to improve public health and the overall health policy goals., (© 2019 Nordic Association for the Publication of BCPT (former Nordic Pharmacological Society).)

Statement of the Problem: Several additives have been introduced to decrease the setting time of MTA (mineral trioxide aggregate). For clinical applications, it is essential to investigate the biocompatibility of these materials., Purpose: The present study evaluated the tissue response to MTA that has been separately mixed with citric acid, calcium lactate gluconate (CLG), and Na 2 HPO 4 ., Materials and Method: In this experimental study Twenty one Wistar rats were divided into three groups of 7, 14 and 30 days follow up periods. Sterile polyethylene tubes were subsequently filled with MTA separately mixed with distilled water, 0.1% citric acid, 0.43% calcium lactate gluconate (CLG) and 15% Na 2 HPO 4 and afterwards implanted subcutaneously. Empty tubes were implanted as negative control. At the end of their respective periods, the animals were sacrificed by anesthetic overdose and a biopsy was performed. The inflammatory responses were scored, classified and statistically analyzed using Kruskal-Wallis and Man-Whitney tests. Statistical significance was defined as p < 0.05., Results: There was no significant difference between test groups in any time period after implantation but the mean values of inflammatory responses were significantly more than that of the negative control group ( p > 0.05). The mean values of inflammatory responses were decreasing over time in all test groups. These values did not significantly differ in any group except the CLG and Na 2 HPO 4 groups., Conclusion: The inflammatory responses induced by MTA mixed with citric acid and MTA mixed with Na 2 HPO 4 were comparable to that of the control MTA. MTA mixed with CLG provoked a moderate-to-severe inflammatory response at 7 days after implantation, so further study is required before clinical application of this cement., (Copyright: © 2020: Journal of dentistry (Shiraz).)

A new species of Biskratrombium (Trombidiformes: Microtrombidiidae), B. persicumn. sp. is described and illustrated, from Fars province, southern Iran. Biskratrombium persicum larvae are ectoparasites of the adults of Phlebotomus (Paraphlebotomus) alexandri (Sinton, 1928), P. (Phlebotomus) papatasi (Scopoli, 1786) and Sergentomyia (Sergentomyia) mervynae (Pringle, 1953) (Diptera: Psychodidae). Fars province is considered as a significant focus of leishmaniasis, a disease which is mostly associated with rural areas; these areas offer favorable habitats to the phlebotomine sandflies due to limited sanitation. This study was performed to identify the natural enemies of sandflies (as leishmania disease vectors) in this region. In this research, B. persicum larvae were removed from their sandfly hosts collected from foci of leishmaniasis (e.g., sheep and goat keeping locations) using sticky traps. Also, the abundance of sandflies infested with the parasitic mite was calculated. Some morphological abnormalities in the species are noted and world parasitengone mites parasitizing phlebotomine sandflies are reviewed.

The role of RNA-dependent protein kinase R (PKR) and its association with misfolded protein expression in cancer cells are unclear. Herein we report that PKR regulates misfolded protein clearance by preventing it release through exosomes and promoting lysosomal degradation of misfolded prion proteins in cancer cells. We demonstrated that PKR contributes to the lysosome function and regulates misfolded prion protein clearance. We hypothesized that PKR-associated lysosome function is critical for cancer but not normal cell survival, representing an effective approach for highly targeted cancer therapy. In screening a compound library, we identified two PKR-associated compounds 1 and 2 (Pac 1 and 2) did not affect normal cells but selectively induced cell death in cancer cells depending on their PKR expression status. Pac 1 significantly inhibited the growth of human lung and breast xenograft tumors in mice with no toxicity. Pac 1 binds to PI4K2A and disrupts the PKR/PI4K2A-associated lysosome complex, contributing to destabilization of cancer cell lysosomes and triggering cell death. We observed that PKR and PI4K2A play significant prognostic roles in breast cancer patients. These results demonstrate that targeting of a PI4K2A/PKR lysosome complex may be an effective approach for cancer therapy.

Human tumor xenograft models do not replicate the human immune system and tumor microenvironment. We developed an improved humanized mouse model, derived from fresh cord blood CD34 + stem cells (CD34 + HSC), and combined it with lung cancer cell line-derived human xenografts or patient-derived xenografts (Hu-PDX). Fresh CD34 + HSCs could reconstitute detectable mature human leukocytes (hCD45 + ) in mice at four weeks without the onset of graft-versus-host disease (GVHD). Repopulated human T cells, B cells, natural killer (NK) cells, dendritic cells (DC), and myeloid-derived suppressor cells (MDSC) increased in peripheral blood, spleen, and bone marrow over time. Although cultured CD34 + HSCs labeled with luciferase could be detected in mice, the cultured HSCs did not develop into mature human immune cells by four weeks, unlike fresh CD34 + HSCs. Ex vivo , reconstituted T cells, obtained from the tumor-bearing humanized mice, secreted IFNγ upon treatment with phorbol myristate acetate (PMA) or exposure to human A549 lung tumor cells and mediated antigen-specific CTL responses, indicating functional activity. Growth of engrafted PDXs and tumor xenografts was not dependent on the human leukocyte antigen status of the donor. Treatment with the anti-PD-1 checkpoint inhibitors pembrolizumab or nivolumab inhibited tumor growth in humanized mice significantly, and correlated with an increased number of CTLs and decreased MDSCs, regardless of the donor HLA type. In conclusion, fresh CD34 + HSCs are more effective than their expanded counterparts in humanizing mice, and do so in a shorter time. The Hu-PDX model provides an improved platform for evaluation of immunotherapy., (©2019 American Association for Cancer Research.)

The need for simple and reliable means of respiratory monitoring has existed since the beginnings of medicine. In the present study, we describe the use of color spectrographic analysis of breathing sounds recorded from the external ear canal as a candidate technology to meet this need. A miniature electret microphone was modified with the addition of an adapter to allow it to be placed comfortably in the external ear canal. The amplified signal was then connected to a real-time color spectrogram program running on a laptop personal computer utilizing the Windows operating system. Based on the results obtained, we hypothesize that the real-time display of color spectrogram breathing patterns locally or at a central monitoring station may turn out to be a useful means of respiratory monitoring in patients at increased risk of respiratory depression or other respiratory problems. Finally, we conducted a statistical analysis that suggests that significant spectrogram differences may exist among some groups investigated in the study., (© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society.)

Aim: The aim of this study was to compare the Helicobacter pylori (HP) eradication regimens in patients with end stage renal disease., Background: In patients undergoing hemodialysis, the pathologic changes seen in the stomach may be the result of high serum levels of gastrin, delayed gastric emptying or HP infection., Methods: Our study was a randomized clinical trial in which 120 patients with ESRD (Patients who undergo hemodialysis) confirmed HP infection, were divided to four groups having 2-week eradication regimens; Group I: LCA (lansoprazole 30 mg-BD,clarithromycin 250 mg-BD, amoxicillin 500 mg-BD), Group II: LCM (lansoprazole 30 mg-BD,clarithromycin 250 mg-BD, metronidazole 500 mg-BD), Group III: LCAM (lansoprazole 30 mg-BD,clarithromycin 250 mg-BD,amoxicillin 500 mg-BD, metronidazole 500 mg-BD) and Group IV: Sequential (lansoprazole 30 mg-BDfor two weeks; first week: amoxicillin 500 mg-BD and second week: clarithromycin 250 mg-BD, metronidazole 500 mg-BD).6 weeks after treatment, Urea Breath Test (UBT) was performed for all patients., Results: The mean age of patients was 43.1±11.2 years. 55.8% of patients were male. The success rates of HP eradication in 4 groups were76.7%, 70%, 90% and 90%, respectively. HP eradication rates were not statistically different among the regimens (p=0.11). There were not significant differences among the groups regarding demographic and anthropometric variables., Conclusion: The results showed there was no significant difference between the success rates of HP eradication regimens for ESRD patients. According to approved regimen for 90% eradication rate, with a lower number of medications and given the less risk of side effects and drug interactions, the sequential regimen is the best.

A handful of work focused on improving the intrinsic low mechanical properties of hydroxyapatite (HA) by various reinforcing agents. However, the big challenge regarding improving mechanical properties is maintaining bioactivity. To address this issue, we report fabrication of apatite-based composites by incorporation of alumina nanoparticles (n-Al 2 O 3 ). Although numerous studies have used micron or submicron alumina for reinforcing hydroxyapatite, only few reports are available about the use of n-Al 2 O 3 . In this study, spark plasma sintering (SPS) method was utilized to develop HA-nAl 2 O 3 dense bodies. Compared to the conventional sintering, decomposition of HA and formation of calcium aluminates phases are restricted using SPS. Moreover, n-Al 2 O 3 acts as a bioactive agent while its conventional form is an inert bioceramics. The addition of n-Al 2 O 3 resulted in 40% improvement in hardness along with a 110% increase in fracture toughness, while attaining nearly full dense bodies. The in vitro characterization of nanocomposite demonstrated improved bone-specific cell function markers as evidenced by cell attachment and proliferation, alkaline phosphatase activity, calcium and collagen detection and nitric oxide production. Specifically, gene expression analysis demonstrated that introduction of n-Al 2 O 3 in HA matrix resulted in accelerated osteogenic differentiation of osteoblast and mesenchymal stem cells, as expression of Runx-2 and OSP showed 2.5 and 19.6 fold increase after 2 weeks ( p < 0.05). Moreover, protein adsorption analysis showed enhanced adsorption of plasma proteins to HA-nAl 2 O 3 sample compared to HA. These findings suggest that HA-nAl 2 O 3 could be a prospective candidate for orthopedic applications due to its improved mechanical and osteogenic properties.

Follicle culture provides a condition which can help investigators to evaluate various aspects of ovarian follicle growth and development and impact of different components and supplementations as well as presumably application of follicle culture approach in fertility preservation procedures. Mesenchymal Stem Cells (MSCs), particularly those isolated from menstrual blood has the potential to be used as a tool for improvement of fertility. In the current study, a 3D co-culture system with mice preantral follicles and human Menstrual Blood Mesenchymal Stem Cells (MenSCs) using either collagen or alginate beads was designed to investigate whether this system allows better preantral follicles growth and development. Results showed that MenSCs increase the indices of follicular growth including survival rate, diameter, and antrum formation as well as the rate of in vitro maturation (IVM) in both collagen and alginates beads. Although statistically not significant, alginate was found to be superior in terms of supporting survival rate and antrum formation. Hormone assay demonstrated that the amount of secreted 17 β-estradiol and progesterone in both 3D systems increased dramatically after 12 days, with the highest levels in system employing MenSCs. Data also demonstrated that relative expression of studied genes increased for Bmp15 and Gdf9 and decreased for Mater when follicles were cultured in the presence of MenSCs. Collectively, results of the present study showed that MenSCs could improve indices of follicular growth and maturation in vitro. Further studies are needed before a clinical application of MenSCs-induced IVM is considered., (Copyright © 2018 Society for Biology of Reproduction & the Institute of Animal Reproduction and Food Research of Polish Academy of Sciences in Olsztyn. All rights reserved.)

Expression of the multikinase inhibitor encoded by the tumor suppressor gene TUSC2 (also known as FUS1 ) is lost or decreased in non-small cell lung carcinoma (NSCLC). TUSC2 delivered systemically by nanovesicles has mediated tumor regression in clinical trials. Because of the role of TUSC2 in regulating immune cells, we assessed TUSC2 efficacy on antitumor immune responses alone and in combination with anti-PD-1 in two Kras -mutant syngeneic mouse lung cancer models. TUSC2 alone significantly reduced tumor growth and prolonged survival compared with anti-PD-1. When combined, this effect was significantly enhanced, and correlated with a pronounced increases in circulating and splenic natural killer (NK) cells and CD8 + T cells, and a decrease in regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), and T-cell checkpoint receptors PD-1, CTLA-4, and TIM-3. TUSC2 combined with anti-PD-1 induced tumor infiltrating more than NK and CD8 + T cells and fewer MDSCs and Tregs than each agent alone, both in subcutaneous tumor and in lung metastases. NK-cell depletion abrogated the antitumor effect and Th1-mediated immune response of this combination, indicating that NK cells mediate TUSC2/anti-PD-1 synergy. Release of IL15 and IL18 cytokines and expression of the IL15Rα chain and IL18R1 were associated with NK-cell activation by TUSC2. Immune response-related gene expression in the tumor microenvironment was altered by combination treatment. These data provide a rationale for immunogene therapy combined with immune checkpoint blockade in the treatment of NSCLC. Cancer Immunol Res; 6(2); 163-77. ©2018 AACR ., (©2018 American Association for Cancer Research.)