Search

Given the rise of multidrug-resistant (MDR) Pseudomonas aeruginosa infections, alternative treatments are needed. Anti-pseudomonal phage therapy shows promise, but its clinical application is limited due to the development of resistance and a lack of biofilm penetration. Recently, adjuvants like CaEDTA have shown the ability to enhance the effectiveness of combined antimicrobial agents. Here, we tested a phage-adjuvant combination and demonstrated the effectiveness of intranasally inhaled phage (KKP10) + CaEDTA in addition to ceftazidime/avibactam (CZA) for chronic P. aeruginosa lung infections. The results emphasize that intranasal inhalation of phage along with CaEDTA can successfully re-sensitize MDR P. aeruginosa to CZA in a triple combination treatment. This promising approach shows potential as a therapy for chronic respiratory tract infections., Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 The Authors. Published by Elsevier Masson SAS.. All rights reserved.)

High population density and tourism in Southeast Asia increase the risk of mpox due to frequent interpersonal contacts. Our wastewater surveillance in six Southeast Asian countries revealed positive signals for Monkeypox virus (MPXV) DNA, indicating local transmission. This alerts clinicians and helps allocate resources like testing, vaccines and therapeutics in resource-limited countries., (© International Society of Travel Medicine 2023. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Cryopreservation is a way to preserve germplasm with applications in agriculture, biotechnology, and conservation of endangered animals. Cryopreservation has been available for over a century, yet, using current methods, only around 50% of spermatozoa retain their viability after cryopreservation. This loss is associated with damage to different sperm components including the plasma membrane, nucleus, mitochondria, proteins, mRNAs, and microRNAs. To mitigate this damage, conventional strategies use chemical additives that include classical cryoprotectants such as glycerol, as well as antioxidants, fatty acids, sugars, amino acids, and membrane stabilizers. However, clearly current protocols do not prevent all damage. This may be due to the imperfect function of antioxidants and the probable conversion of media components to more toxic forms during cryopreservation.

CAR T cell treatment of solid tumours is limited by poor persistence partly due to CD95 ligand (CD95L)-induced apoptosis. Both T cells and cells within the tumour microenvironment (TME) may express CD95L, triggering apoptosis in CD95-receptor-positive CAR T cells. Tonic signalling of CAR T cells may also increase CD95-dependent AICD. Because the intracellular protein c-FLIP protects T cells from AICD, we expressed c-FLIPp43 within a Her-2 targeted CAR cassette and evaluated the potential of c-FLIPp43 through in vitro functional assays and in vivo tumour-bearing xenograft model. cFLIP expression protected against CD95L-induced cell death in the Jurkat T cell lines. However, in primary human CAR T cells containing CAR-CD28 domains, c-FLIPp43 overexpression had minimal additional impact on resistance to CD95L-induded cell death. In vitro cytotoxicity against a breast cancer tumour cell line was not altered by c-FLIPp43 expression, but the expression of c-FLIPp43 in Her2-CAR T cells lowered interferon-γ secretion, without markedly affecting IL-2 levels, and c-FLIPp43-Her2-CAR T cells showed reduced anti-tumour activity in immunodeficient mice with breast cancer. The findings of this study provide a new understanding of the effects of controlling extrinsic apoptosis pathway suppression in CAR T cells, suggesting that c-FLIPp43 expression reduces anti-tumour immunity through the modulation of effector T cell pathways.

Reactive oxygen species are associated with cryodamage and may be a factor causing or exacerbating cellular cryodamage during freezing and thawing processes. Induction of sublethal oxidative stress as a new approach for preconditioning of sperm improves the cryo-resistance of sperm. The aim of this study was to investigate effects of sublethal concentrations of xanthine oxidase (XO), which induces oxidative stress before cryopreservation on values for semen quality variables of rooster sperm post-thawing. Semen samples were collected from 15 roosters and treated with different concentrations of XO [XO-0, XO-0.005, XO-0.05, XO-0.5, XO-5, and XO-50 U/ml]; then, the effects of treatments with XO as sublethal stressors, were examined. Results indicated the XO-0.5 and XO-5 treatments resulted in a greater percentage of sperm total motility, progressive motility, viability, and membrane functionality compared to other groups. There was no difference after treatments with XO-0, XO-0.005, and XO-0.05 on sperm total motility, membrane functionality, apoptosis, mitochondria activity, and viability. There was a greater percentage of mitochondria activity in sperm of the XO-0.05, XO-0.5, and XO-5 groups. Furthermore, there was the greatest concentration of malondialdehyde (MDA) in samples of the XO-50 group. Values for sperm abnormal morphology, acrosome integrity, and DNA fragmentation were not different among samples post-thawing. Sperm treated with XO-0.5 and XO-5 had a greater fertilization capacity than those of the control group. In conclusion, treatment of sperm with 0.5 and 5 U/ml XO as inducers of mild oxidative stress before cryopreservation, improved several function quality indices of sperm post-thawing., (Copyright © 2021 Elsevier B.V. All rights reserved.)

Mcl-1 is a member of the Bcl-2 anti-apoptotic protein family with important roles in the development, lifespan and metabolism of lymphocytes, as well as oncogenesis. Mcl-1 displays the shortest half-life of all Bcl-2 family members, with miRNA interference and proteasomal degradation being major pathways for Mcl-1 downregulation. In this study, we have identified a previously undescribed control mechanism active at the RNA level. A divergently transcribed lncRNA LOC107985203 (named here mcl1-AS1) negatively modulated Mcl-1 expression resulting in downregulation of Mcl-1 at both mRNA and protein level in a time-dependent manner. Using reporter assays, we confirmed that the mcl1-AS1 lncRNA promoter was located within Mcl-1 coding region. We next placed mcl1-AS1 under tetracycline-inducible control and demonstrated decreased viability in HEK293 cells upon doxycycline induction. Inhibition of mcl1-AS1 with shRNA reversed drug sensitivity. Bioinformatics surveys predicted direct mcl1-AS1 lncRNA binding to Mcl-1 transcripts, suggesting its mechanism in Mcl-1 expression is at the transcriptional level, consistent with a common role for anti-sense transcripts. The identification of a bi-directional promoter and lncRNA controlling Mcl-1 expression will have implications for controlling Mcl-1 activity in cancer cells, or for the purpose of enhancing the lifespan and quality of anti-cancer T lymphocytes., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Regulated expression of genetic elements that either encode polypeptides or various types of functional RNA is a fundamental goal for gene therapy. Inducible expression may be preferred over constitutive promoters to allow clinician-based control of gene expression. Existing Tet-On systems represent one of the tightest rheostats for control of gene expression in mammals. However, basal expression in absence of tetracycline compromises the widespread application of Tet-controlled systems in gene therapy. We demonstrate that the order of P2A-linked genes of interest was critical for maximal response and tightness of a chimeric antigen receptor (CAR)-based construct. The introduction of G72V mutation in the activation region of the TetR component of the rtTA further improved the fold response. Although the G72V mutation resulted in a removal of a cryptic splice site within rtTA, additional removal of this splice site led to only a modest improvement in the fold-response. Selective removal of key promoter elements (namely the BRE, TATA box, DPE and the four predicted Inr) confirmed the suitability of the minimal CMV promoter and its downstream sequences for supporting inducible expression. The results demonstrate marked improvement of the rtTA based Tet-On system in Sleeping Beauty for applications such as CAR T cell therapy.

It is now becoming clear that less differentiated naive and memory T cells are superior to effector T cells in the transfer of immunity for adoptive cell therapy. This review will outline the challenges faced by chimeric antigen receptor (CAR) T cell therapy in the generation of persistence and memory for CAR T cells, and summarize recent strategies to improve CAR T cell persistence, with a focus on memory cell formation. The relevance of enhancing persistence in more differentiated effector T cells is also covered, because genetic and pharmacological interventions may prolong effector T cell activity and lifespan, thereby improving anti-cancer activity. In particular, it may be possible to enforce epigenetic changes in differentiated T cells to enhance memory CAR T cell formation. Optimizing the generation of self-renewing T cell populations (e.g. memory cells), while maintaining differentiated effector T cells through epigenome modification, will help overcome barriers to T cell expansion and survival, thereby improving clinical outcomes in CAR T cell therapy., (© 2019 Australian and New Zealand Society for Immunology Inc.)

Having a high proportion of polyunsaturated fatty acids avian spermatozoa predispose to lipoperoxidation which results in fertility reduction. In the current study, rosemary leaves powder (RLP) was fed to senescent breeder roosters to improve their reproductive performance. Twenty four 70-week-old roosters were randomly divided into four groups and received following treatments including 0 (RLP-0), 2.5 (RLP-2.5), 5 (RLP-5) or 7.5 (RLP-7.5) g of RLP/kg of diet for eight consecutive weeks. Semen characteristics were evaluated weekly. Sperm penetration rate was assessed once, however, fertility, hatchability, embryonic mortality and hatchling quality evaluated twice (using eggs collected during 1st and 2nd weeks following AI) at the end of experiment. Excluding body weight and sperm abnormality percentage, other traits including semen concentration (RLP-2.5 = 3.57, RLP-5 = 4.21 and RLP-7.5 = 3.79; SEM = 0.12; p < 0.01), total sperm production (RLP-2.5 = 1.33, RLP-5 = 1.8 and RLP-7.5 = 1.47; SEM = 0.07; p < 0.01), forward motility (RLP-2.5 = 72.96, RLP-5 = 83.65 and RLP-7.5 = 78.84; SEM = 0.47; p < 0.01) and viability (RLP-2.5 = 82.93, RLP-5 = 88.69 and RLP-7.5 = 86.85; SEM = 0.45; p < 0.01) were improved in RLP treated groups compared to control group (3.08 ± 0.12, 1.05 ± 0.07, 68.39 ± 0.47 and 76 ± 0.45 for semen concentration, total sperm production, sperm forward motility and viability, respectively). In addition, semen volume and sperm plasma membrane functionality were higher in both RLP-5 (0.43 ± 0.01 and 66.66 ± 0.55) and RLP-7.5 (0.39 ± 0.01 and 65.52 ± 0.55) than control group (0.34 ± 0.01; p < 0.05 and 62.89 ± 0.55; p < 0.05). Supplementation of RLP significantly decreased semen Malondialdehyde (MDA) concentration. Moderate level of RLP (RLP-5) had significantly higher numbers of sperm penetration holes compared to other groups. Fertility rate of collected eggs from both RLP-5 (first week: 91.09 ± 1.27 (P < 0.01); second week: 88.73 ± 1.27 (p < 0.05)) and RLP-7.5 (first week: 93.11 ± 1.27 (P < 0.01); second week: 90.87 ± 1.27 (p < 0.05)) groups was higher than other groups at 1st and 2nd weeks of egg collection. Hatchability of eggs set at 2nd week (83.64 ± 3.54; p < 0.05) was higher and embryonic mortality at 1st week (1-6 day mortality: 5.03 ± 1.25 (p < 0.05); 18-21 day and pipped mortality: 8.55 ± 1.31 (p < 0.05)) was in RLP-0.5 group than other groups, respectively. To conclude, RLP supplementation could successfully attenuate age-related sub-fertility in senescent roosters. Further studies are needed to divulge the causal mechanisms involved., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Embryonic stem cells (ESCs) are derived from inner cell mass (ICM) and have the potency to differentiate into three germ layers (ectoderm, endoderm, and mesoderm). This potency of ESCs, called pluripotency, is critical for maintaining stemness. Transcriptional regulatory circuitry preserving stemness consists of transcription factors (TFs), epigenetic mechanisms, microRNAs (miRNAs or miRs), and long non-coding RNAs (lncRNAs). In this circuitry, components assist each other to activate essential genes for maintaining pluripotency and suppressing lineage-specific genes. TFs act directly by binding to their binding sites in the genome or indirectly by activating another gene (such as a miR), epigenetic mechanisms play their role by providing an activatory or inhibitory context for transcription, miRNAs regulate gene expression at the post-transcriptional level, and lncRNAs act as a scaffold function for epigenetic elements, regulating gene expression in ESCs. All these factors create a crossroad and collaborate to sustain stemness in the ESCs. Herein, we explain the role of each member in this circuitry and demonstrate the significance of the crossroad for keeping stemness., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

The sprouting of new blood vessels by angiogenesis is critical in vascular development and homeostasis. Aberrant angiogenesis leads to enormous pathological conditions such as ischemia and cancer. MicroRNAs (also known as miRNAs or miRs) play key roles in regulation of a range of cellular processes by posttranscriptional suppression of their target genes. Recently, new studies have indicated that miRNAs are involved in certain angiogenic settings and signaling pathways use these non-coding RNAs to promote or suppress angiogenic processes. Herein, VEGFR2 and FGFR1 were identified as miR-129-1 and miR-133 targets using bioinformatic algorithms, respectively. Afterwards, using luciferase reporter assay and gene expression analysis at both mRNA and protein levels, VEGFR2 and FGFR1 were validated as miR-129-1 and miR-133 targets. In addition, we showed that miR-129-1 and miR-133 suppress angiogenesis properties such as proliferation rate, cell viability, and migration activity of human umbilical vein endothelial cells (HUVEC) in vitro. We conclude that these miRNAs can suppress key factors of angiogenesis by directly targeting them. These results have important therapeutic implications for a variety of diseases involving deregulation of angiogenesis, including cancer.

Background: MicroRNA-129-1 (miR-129-1) seems to behave as a tumour suppressor since its decreased expression is associated with different tumours such as glioblastoma multiforme (GBM). GBM is the most common form of brain tumours originating from glial cells. The impact of miR-129-1 downregulation on GBM pathogenesis has yet to be elucidated., Methods: MiR-129-1 was overexpressed in GBM cells, and its effect on proliferation was investigated by cell cycle assay. MiR-129-1 predicted targets (CDK6, IGF1, HDAC2, IGF2BP3 and MAPK1) were also evaluated by western blot and luciferase assay., Results: Restoration of miR-129-1 reduced cell proliferation and induced G1 accumulation, significantly. Several functional assays confirmed IGF2BP3, MAPK1 and CDK6 as targets of miR-129-1. Despite the fact that IGF1 expression can be suppressed by miR-129-1, through 3'-untranslated region complementary sequence, we could not find any association between IGF1 expression and GBM. MiR-129-1 expression inversely correlates with CDK6, IGF2BP3 and MAPK1 in primary clinical samples., Conclusion: This is the first study to propose miR129-1 as a negative regulator of IGF2BP3 and MAPK1 and also a cell cycle arrest inducer in GBM cells. Our data suggests miR-129-1 as a potential tumour suppressor and presents a rationale for the use of miR-129-1 as a novel strategy to improve treatment response in GBM., (Published by the BMJ Publishing Group Limited. For permission to use (where not already granted under a licence) please go to http://www.bmj.com/company/products-services/rights-and-licensing/)

Viral vectors have a wide range of applications in biology, particularly in gene therapy. Based on their integration capacity, viral vectors are classified as either integrating or non-integrating vectors. Although integrating vectors, such as lentivectors, have the ability to direct prolonged expression of exogenous genes, manipulation of the host genome is an inappropriate feature of these gene delivery tools. Non-integrating vectors, such as episomal replicating plasmids, can replicate and persist in host cells for long periods without any chromosomal interruption. These advantages made them good tools for gene induction purposes in gene therapy and basic studies. Due to the necessity of gene induction in stem cells for study of mammalian development and targeted differentiation, the use of integrating vectors for prolonged expression of genes of interest has been developed. Application of replicating plasmids can overcome some drawbacks associated with integrating vectors, although replication and maintenance of these plasmids can differ between cell types. Previously, it has been shown that such plasmids can be maintained in human embryonic stem cells for more than one month, but the rate of the plasmid replication during the host cell cycle has not been elucidated. In the present study, we showed that an EBV-based plasmid can replicate simultaneously with host in pluripotent and multipotent human and mouse stem cells and can be sustained for long time periods in dividing cells., (© 2015 American Institute of Chemical Engineers.)

Background: Articular cartilage injuries are a common clinical problem at the time of ACL reconstruction with an incidence rate of 16-46%. Good results of ACL reconstruction combined with the treatment of chondral lesions have been published in some studies., Method: After statistical analysis 30 patients were selected and divided in 2 groups. The first group consisted of 15 patients with isolated ACL tear without any other concomitant injuries and the second group consisted of 15 patients with ACL tear and concomitant high grade (grade 3 or 4 of outerbridge classification) contained articular cartilage injuries during arthroscopy. Group 1 underwent ACL reconstruction and group 2 underwent ACL reconstruction combined with chondroplasty via the drilling or microfracture technique. For each patient the Lysholm knee score questionnaire was completed before surgery, 6 months and 1 year after surgery., Results: The mean Lysholm knee score in both groups improves: 9.6 points after 6 months and 16.06 points after 1 year in group 1, 23.26 points after 6 months, 30.66 after 1 year in group 2, which was statistically significant (Pvalue<0.05)., Conclusion: Improvement in the Lysholm knee score in both groups shows that ACL reconstruction with concomitant chondroplasty in high grade chondral injuries has good results with patient satisfaction and improvement in their quality of life.

Recent advances in small RNA research have implicated microRNAs (miRNAs) as important regulators of proliferation and development. The miR-371-373 cluster is prominently expressed in human embryonic stem cells (ESCs) and rapidly decreases after cell differentiation. MiR-371-373 cluster was investigated as one of the key factors of stem cell maintenance and pluripotency in unrestricted somatic stem cells (USSCs) using a lentivirus system. Gene expression showed a dual effect on proliferation, which revealed a transient cell cycle progression and consequent repression in pluripotency factors and cell cycle genes. Cell proliferation analysis with CFU, MTT, and DNA content assays further confirmed the dual effect of cluster after prolonged exposure. Analyzing the course of action, it seems that miR-371-373 cluster acts as an onco/tumor suppressor-miR. MiR371-373 cluster acts by modulating the function of these factors and limiting the excessive cell cycle propagation upon oncogenic stimuli to protect cells from replicative stress, but also activate CDK inhibitors and transcriptional repressors of the retinoblastoma family to cause cell cycle arrest. In contrast to the previous studies, we believe that miR-371-373 cluster functions as a self-renewal miRNA to induce and maintain the pluripotent state but also to potentially inhibit dysregulated proliferation through cell cycle arrest. It seems that miR-371-373 cluster presents with a dual effect in this cellular context which may possess different actions in various cells. This not only expands the basic knowledge of the cluster but may offer a great chance for therapeutic interventions.

Introduction: Chronic myeloid leukemia (CML) is caused by reciprocal translocation in hematopoietic stem cells (HSCs). This translocation forms the BCR-ABL1 oncogene, which alters several signaling pathways that control malignancy. CML has three phases: chronic, accelerated, and blast crisis. The microRNAs (miRNAs or miRs) are noncoding RNAs that downregulate their target gene by targeting 3' UTR of mRNA or through translational inhibition. It has been shown that miRNAs regulate many biological processes, and dysregulation of these regulatory RNAs is involved in disease development, particularly in cancer. The important role of miRNAs as therapeutic agents and biomarkers has been demonstrated in CML patients at different phases of the disease., Methods: Stem-loop reverse transcription polymerase chain reaction was used to characterize differentially expressed miRNAs of leukocytes in the peripheral blood of 50 newly diagnosed CML patients in chronic phase., Results: Some onco-miRNAs were found to be downregulated (miR-155 and miR-106), and some tumor suppressor miRs (miR-16-1, miR-15a, miR-101, miR-568) were upregulated., Conclusion: These results show that very few miRNAs alone would be good candidates for CML diagnosis independently of conflicting results, but together could be an additional tool for CML diagnosis. Moreover, miRNAs might be good candidates for prognosis prediction and CML therapy., (© 2015 John Wiley & Sons Ltd.)

Gene therapy as a therapeutic approach has been the dream for many scientists around the globe. Many strategies have been proposed and applied for this purpose, yet the void for a functional safe method is still apparent. Since most of the diseases are caused by undesirable upregulation (oncogenes) or downregulation (tumor suppressor genes) of genes, major gene therapy's techniques affect gene expression. Most of the methods are used in post-transcriptional level such as RNA inhibitory (RNAi) and splice-switching oligonucleotides (SSOs). RNAi blocks messenger RNA (mRNA) translation by mRNA degradation or interruption between attachments of mRNA with ribosomes' subunits. However, one of the novel methods is the usage of transcription factor targeted decoys. DNA decoys are the new generation of functional gene downregulatory oligonucleotides which compete with specific binding sites of transcription factors. Considering the exponential growth of this technique in both in vitro and in vivo studies, in this paper, we aim to line out the description, design, and application of decoys in research and therapy.

MicroRNAs (miRNA) are a large family of small single-stranded RNA molecules found in all multicellular organisms. Early studies have been shown that miRNA are involved in cancer development and progression, and this role can be done by working as an oncogenes and tumor suppressor genes, so manipulation of this molecules can be a promising approach in cancer therapy, and experimental results represented that the modification in breast cancer phenotype is possible by miRNA expression alteration. miR-16, which is located in 13q14 chromosome, plays critical roles as a tumor suppressor by targeting several oncogenes which regulate cell cycle and apoptosis. Hence, in the present study, we investigated whether miR-16 could decline growth and survival of MCF-7 cell line as model of human breast cancer. MCF-7 cell line was infected with lentiviruses containing miR-16 precursor sequence. The effects of ectopic expression of miR-16 on breast cancer phenotype were examined by cell cycle analysis and apoptosis assays. miR-16 cytotoxicity effect was measured by the MTT assay. We showed that the miR-16 overexpression reduces Cyclin D1 and BCL2 at messenger RNA (mRNA) and protein levels in MCF-7 cell line. In addition, this is found that enforced expression of miR-16 decreases cell growth and proliferation and induces apoptosis in MCF-7 cells. In conclusion, our results revealed that upregulation of miR-16 would be a potential approach for breast cancer therapy.

Transcription factor decoys (TFDs) are exogenous oligonucleotides which can compete by cis-elements in promoters or enhancers for binding to TFs and downregulating gene expression in a specific manner. It is believed that tumor mass originates from cancer stem cells (CSCs) which the same with embryonic stem cells (ESCs) have the properties of both pluripotency and self-renewal (stemness). Many transcription factors such as Nanog, Oct-4, Sox2, Klf4, and Sall4 act as master regulators in the maintenance of stemness in both cell types. Differentiation therapy is based on this theory that by differentiation of CSCs, tumor mass can be eliminated with common cancer therapy methods. To our knowledge, the present study is the first report of a TFD approach against master regulator of stemness, Nanog, Oct-4, and Klf4, for downregulation purposes in P19 embryonic carcinoma stem cell. Different simple and complex decoys against Nanog, OCT-4, Sox2, and Klf4 were designed and used for this purpose. The results showed that the applied decoys especially Nanog-specific decoy decreased the expression of downstream genes.

Objective: The purpose of this study was to compare the effect of dual tasking on postural and cognitive performance between participants with and without nonspecific chronic low back pain., Methods: In this 3-factor mixed-design study, dynamic postural stability was assessed in 15 patients with chronic nonspecific low back pain and 15 age-, sex-, and size-matched asymptomatic participants. Bilateral stance on a Biodex Balance System was investigated at 3 levels of postural task difficulty (different platform stabilities levels with eyes open and closed) and 2 levels of cognitive task difficulty (with or without auditory Stroop test). We measured anterior-posterior, medial-lateral, and overall indices for postural performance. Average reaction time and error ratio of a modified auditory Stroop test were calculated as measures of the cognitive task performance., Results: Mixed-design 3-way analyses of variance revealed significant interactions. Post hoc 2-way analyses of variance showed significant group by cognitive task difficulty for anterior-posterior (P < .001), medial-lateral (P = .003), and overall stability indices (P < .001) on a stiffness level of 5 with eyes closed. At this level, there were significant differences between single- and dual-task conditions for anterior-posterior (P < .001), medial-lateral (P = .02), and overall stability indices (P < .001) only in the chronic low back pain group. Also, at the most difficult postural conditions, participants with chronic low back pain increased their error ratio (P = .002), whereas matched asymptomatic individuals increased their reaction time (P < .01) of the auditory Stroop test., Conclusion: Postural task performance is attenuated by cognitive loading at a moderate level of postural task difficulty. Therefore, to observe the effect of attentional demands of postural control, task difficulty should be considered., (Copyright © 2014 National University of Health Sciences. Published by Mosby, Inc. All rights reserved.)

Cancer is one of the most important diseases of humans, for which no cure has been found so far. Understanding the causes of cancer can pave the way for its treatment. Alteration in genetic elements such as oncogenes and tumor suppressor genes results in cancer. The most recent theory for the origin of cancer has been provided by cancer stem cells (CSCs). Tumor-initiating cells (T-ICs) or CSCs are a small population isolated from tumors and hematologic malignancies. Since CSCs are similar to embryonic stem cells (ESCs) in many aspects (such as pluripotency and self-renewal), recognizing the signaling pathways through which ESCs maintain their stemness can also help identify CSC signaling. One component of these signaling pathways is non-coding RNAs (ncRNAs). ncRNAs are classified in two groups: microRNAs (miRNAs) and long non-coding RNAs (lncRNAs). miRNAs undergo altered expression in cancer. In this regard, they are classified as Onco-miRNAs or tumor suppressor miRNAs. Some miRNAs play similar roles in ESCs and CSCs, such as let-7 and miR-302. This review focuses on the miRNAs involved in stemness of ESCs and CSCs by presenting a summary of the role of miRNAs in other tumor cells.

Objective: A functional interaction between Catechol-O-Methyltransferase (COMT) Val158Met and methylenetetrahydrofolate reductase (MTHFR) C677T has been shown to differentially affect cognition in patients with schizophrenia and healthy controls; the effect of COMT Val158Met × MTHFR interaction on resilience to stress in patients and controls remains to be examined., Method: A total of 98 patients with non-affective psychotic disorder and 118 controls were genotyped for MTHFR C677T, MTHFR A1298C, and COMTVal158Met. Daily life reactivity to stress, modelled as the effect of daily life stress on psychotic experiences, was measured using the experience sampling method (ESM)., Results: The MTHFR C677T genotype moderated the interaction between COMT Val158Met genotype and stress in patients (P < 0.0001), but not in controls (P = 0.68). Further examination of this interaction revealed that in patients with the MTHFR 677 T-allele, COMT Met/Met individuals displayed the largest increases in psychotic symptoms in reaction to ESM stress [χ(2)(2) = 29.51; P < 0.0001], whereas in patients with the MTHFR 677 C/C genotype no significant COMT Val158Met × ESM stress interaction was apparent [χ(2)(2) = 3.65; P = 0.16]. No moderating effect of MTHFR A1298C was found., Conclusion: Stress reactivity associated with COMT Val158Met in patients with psychosis may crucially depend on MTHFR C677T genotype., (© 2011 John Wiley & Sons A/S.)

Objective: Birth trauma at delivery is a rare but significant prenatal complication. The aim of this study was to determine the incidence of birth trauma and risk factors related to fetal injury., Materials and Methods: Birth trauma was evaluated in singleton fetuses with no major anomalies and with vertex presentations over a 3-year period from 2002 to 2005. One hundred and forty-eight neonates, who experienced birth trauma, were prospectively identified and compared with 280 normal neonates. Both groups were delivered vaginally. Maternal and infant characteristics were evaluated as possible risk factors for fetal injury., Results: Among the 148 infants with birth trauma, nine had multiple injuries. The most common injury was cephalohematoma (n = 77). Other injuries included clavicle fractures (n = 56), brachial plexus paralysis (n = 13), asphyxia (n = 7), facial lacerations (n = 4), brain hemorrhage (n = 1), and skin hematoma (n = 2). Multiple regression analysis identified premature rupture of membranes, instrumental delivery, birth weight, gestational age, induction of labor, and academic degree of attendant physician at delivery as the most significant risk factors for birth trauma., Conclusion: The incidence of birth trauma was 41.16 per 1,000 vaginal deliveries. Induction of labor, premature rupture of membranes, academic degree of attendant physician at delivery, higher birth weight, and gestational age were associated with fetal injuries., (Copyright 2010 Taiwan Association of Obstetrics and Gynecology. Published by Elsevier B.V. All rights reserved.)