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Aberrantly expressed microRNAs play important roles in gastric tumorigenesis. However, use of miRNAs as a therapeutic option in gastric cancer still remains as a challenging problem.
We performed transient transfection of miR-34a-5p mimic and stable transfection of pre-mir-34a into KatoIII cells. Then, we evaluated the effect of transfected miRNAs on numerous cellular and molecular processes.
Following transient transfection of miR-34a-5p mimic at 25 nM-a commonly used concentration-into KatoIII cells, inhibition of two target genes expression, namely Notch1 and β-catenin, was not observed, but a non-significant marginal increase of these genes was detected. No changes were detected in the percentage of apoptotic cells as well as in CD44 + and EpCAM + cells after 25 nM miR-34a-5p mimic transfection. PFK15 molecular weight Interestingly, stable transfection of pre-mir-34a into KatoIII cells (named as KatoIII-pGFPC1-34a cells) caused a significant repression in β-catenin protein and Notch1 mRNA levels (p < 0.05 and p < 0.01, respectively) relative to equivalent control (KatoIII- pGFPC1-empty cells). The percentage of CD44 + cells in the KatoIII-pGFPC1-34a cells (< 40%) was significantly lower than that in control cells (~ 95%) (p < 0.05). An increase of ~ 3.5% in apoptotic cells and a slower proliferation rate were detected in KatoIII-pGFPC1-34a cells.
Our study revealed that the effect of miR mimic in target gene repression can be dependent to its concentration as well as to the cell type. Meanwhile, our findings further support a regulatory function for pre-miRNAs in target repression and will help to develop effective therapeutic strategies in cancer treatment.
Our study revealed that the effect of miR mimic in target gene repression can be dependent to its concentration as well as to the cell type. Meanwhile, our findings further support a regulatory function for pre-miRNAs in target repression and will help to develop effective therapeutic strategies in cancer treatment.
Some studies have stated that intrauterine insemination (IUI) with controlled ovarian stimulation (COS) might increase the pregnancy rate, while others suggest that IUI in the natural cycle (NC) should be the first line of treatment. It remains unclear whether it is necessary to use COS at the same time when IUI is applied to treat isolated male factor infertility. Thus, we aimed to investigate efficacy of IUI with COS for isolated male factor infertility.
A total of 601 IUI cycles from 307 couples who sought medical care for isolated male factor infertility between January 2010 and February 2020 were divided into two groups NC-IUI and COS-IUI. The COS-IUI group was further divided into two subgroups according to the number of pre-ovulatory follicles on the day of HCG cycles with monofollicular development (one follicle group) and cycles with at least two pre-ovulatory follicles (≥ 2 follicles group). The IUI outcomes, including clinical pregnancy, live birth, spontaneous abortion, ectopic pregnancy, and y follicles, the multiple pregnancy rate increased without a substantial gain in overall pregnancy rate; thus, COS should not be preferred in IUI for isolated male factor infertility. If COS is required, one stimulated follicle and one healthy baby should be the goal considering the safety of both mothers and foetuses.
Little previous research has analysed the relationship between schools' indoor air problems and schools' social climate. In this study, we analysed a) whether observed mould and dampness in a school building relates to students' perceptions of school climate (i.e. teacher-student relationships and class spirit) and b) whether reported subjective indoor air quality (IAQ) at the school level mediates this relationship.
The data analysed was created by merging two nationwide data sets survey data from students, including information on subjective IAQ (N = 25,101 students), and data from schools, including information on mould and dampness in school buildings (N = 222). The data was analysed using multilevel mediational models.
After the background variables were adjusted, schools' observed mould and dampness was not significantly related to neither student-perceived teacher-student relationships nor class spirit. However, our mediational models showed that there were significant indirect effects from schools' observed mould and dampness to outcome variables via school-level subjective IAQ a) in schools with mould and dampness, students reported significantly poorer subjective IAQ (standardised β = 0.34, p < 0.001) than in schools without; b) the worse the subjective IAQ at school level, the worse the student-reported teacher-student relationships (β = 0.31, p = 0.001) and class spirit (β = 0.25, p = 0.006).
Problems in a school's indoor environment may impair the school's social climate to the degree that such problems decrease the school's perceived IAQ.
Problems in a school's indoor environment may impair the school's social climate to the degree that such problems decrease the school's perceived IAQ.Lung cancer (LC) is a heterogeneous disease consisting mainly of two subtypes, non-small cell lung cancer (NSCLC) and small cell lung cancer (SCLC), and remains the leading cause of death worldwide. Despite recent advances in therapies, the overall 5-year survival rate of LC remains less than 20%. The efficacy of current therapeutic approaches is compromised by inherent or acquired drug-resistance and severe off-target effects. Therefore, the identification and development of innovative and effective therapeutic approaches are critically desired for LC. The development of RNA-mediated gene inhibition technologies was a turning point in the field of RNA biology. The critical regulatory role of different RNAs in multiple cancer pathways makes them a rich source of targets and innovative tools for developing anticancer therapies. The identification of antisense sequences, short interfering RNAs (siRNAs), microRNAs (miRNAs or miRs), anti-miRs, and mRNA-based platforms holds great promise in preclinical and early clinical evaluation against LC. In the last decade, RNA-based therapies have substantially expanded and tested in clinical trials for multiple malignancies, including LC. This article describes the current understanding of various aspects of RNA-based therapeutics, including modern platforms, modifications, and combinations with chemo-/immunotherapies that have translational potential for LC therapies.
The translocator protein (TSPO) has been identified as a positron emission tomography (PET)-visible biomarker of inflammation and promising immunotherapeutic target for the treatment of Alzheimer's disease (AD). While TSPO ligands have been shown to reduce the accumulation of the toxic Alzheimer's beta-amyloid peptide, their effect on tau pathology has not yet been investigated. To address this, we analyzed the effects of TSPO ligand, Ro5-4864, on the progression of neuropathology in rTg4510 tau transgenic mice (TauTg).
Brain atrophy, tau accumulation, and neuroinflammation were assessed longitudinally using volumetric magnetic resonance imaging, tau-PET, and TSPO-PET, respectively. In vivo neuroimaging results were confirmed by immunohistochemistry for markers of neuronal survival (NeuN), tauopathy (AT8), and inflammation (TSPO, ionized calcium-binding adaptor molecule 1 or IBA-1, and complement component 1q or C1q) in brain sections from scanned mice.
TSPO ligand treatment attenuated brain atrophy and hippocampal neuronal loss in the absence of any detected effect on tau depositions. Atrophy and neuronal loss were strongly associated with in vivo inflammatory signals measured by TSPO-PET, IBA-1, and levels of C1q, a regulator of the complement cascade. In vitro studies confirmed that the TSPO ligand Ro5-4864 reduces C1q expression in a microglial cell line in response to inflammation, reduction of which has been shown in previous studies to protect synapses and neurons in models of tauopathy.
These findings support a protective role for TSPO ligands in tauopathy, reducing neuroinflammation, neurodegeneration, and brain atrophy.
These findings support a protective role for TSPO ligands in tauopathy, reducing neuroinflammation, neurodegeneration, and brain atrophy.
Price promotions on sugar-sweetened beverages (SSBs) are commonly used by retailers to provide economic incentives for purchasing. Surprisingly, there is a lack of high-quality articles that examine the frequency and magnitude of sugary beverage discounting and consumer responses to discounts. The objective of this study is to quantify the association between exposure to price discounts and SSB purchases.
This cross-sectional study linked 2016 SSB consumption data from a U.S. household consumer panel (analytic sample N = 11,299 households) and weekly prices at stores where they shopped. We derived percent of the time SSBs were discounted (annual promotion frequency) and the amount of the discount (annual promotion magnitude) and assessed their association with household annual per capita SSB purchase ounces. Linear regression models adjusted for household size, income per capita, age, education, presence of children, race, occupation, region, and urbanicity. We also evaluated whether the association between promotion and purchase varied by socioeconomic status and race subgroups. Data were analyzed in 2019-2020.
On average, households were exposed to SSBs price promotions 44% of the time. A 10-percentage point increase in annual SSB promotion frequency was associated with 13.7% increase in annual per capita purchasing (P < 0.0001), and a 1-percentage point increase in annual SSB promotion magnitude was associated with 15.3% increase in annual per capita purchasing (P < 0.0001). These associations did no vary significantly across socioeconomic status and race subgroups (Interaction P > 0.2).
More frequent and deeper price promotion was associated with higher annual per capita SSB purchases. Restricting SSB price promotions may be effective at reducing SSB consumption.
More frequent and deeper price promotion was associated with higher annual per capita SSB purchases. Restricting SSB price promotions may be effective at reducing SSB consumption.
The increasing use of metal nanoparticles in industry and biomedicine raises the risk for unintentional exposure. The ability of metal nanoparticles to penetrate the skin ranges from stopping at the stratum corneum to passing below the dermis and entering the systemic circulation. Despite the potential health risks associated with skin exposure to metal nanoparticles, the mechanisms underlying the toxicity of metal nanoparticles on skin keratinocytes remain unclear. In this study, we proposed that exposure of human epidermal keratinocytes (HaCaT) to metal nanoparticles, such as nickel nanoparticles, dysregulates tight-junction associated proteins by interacting with the HIF-1α/miR-29b/MMPs axis.
We performed dose-response and time-response studies in HaCaT cells to observe the effects of Nano-Ni or Nano-TiO
on the expression and activity of MMP-2 and MMP-9, and on the expression of tight junction-associated proteins, TIMP-1, TIMP-2, miR-29b, and HIF-1α. In the dose-response studies, cells were exposed to 0, 10, or 20 μg/mL of Nano-Ni or Nano-TiO
for 24 h.
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