Holbrookbentzen3964

Patients with severe asthma often require oral corticosteroid (OCS) treatment. Clinical trials have demonstrated that mepolizumab can reduce OCS dependence, but real-world data are limited.

To evaluate the impact of mepolizumab on OCS use, asthma exacerbations, and asthma exacerbation-related costs in a real-world setting.

This retrospective cohort study (GSK ID 209642; HO-19-19597) analyzed data from the MarketScan

Commercial database (identification period November 2015-September 2017). Patients were ≥12 years old at mepolizumab initiation (index date), had a baseline asthma diagnosis, and received ≥2 mepolizumab administrations in the first 6 months of follow-up. OCS use, asthma exacerbation rate, and asthma exacerbation-related costs were assessed in the 12-months before (baseline) and 12-months after (follow-up) mepolizumab initiation.

Mepolizumab was associated with a 14.7% reduction in the proportion of patients with ≥1 OCS claim from baseline to follow-up (93.4% vs 79.7%;

<0.001). The mean numbers of OCS claims/patient and OCS bursts (≥20 mg prednisone equivalents for 3‒28 days) between baseline and follow-up were also reduced by 29.1% (

<0.001) and 36.8% (

<0.001), respectively. Reductions in chronic OCS use were demonstrated during follow-up in patients with baseline mean OCS dose ≥5mg and those with a mean OCS dose ≥10mg 90 days before index; the proportion of patients with no OCS use also increased from 6.6% to 20.3% between baseline and follow-up.

Our findings demonstrate that mepolizumab therapy is associated with reduced OCS use in patients treated in a real-world setting, potentially mitigating adverse health sequelae caused by OCS use in these patients.

Our findings demonstrate that mepolizumab therapy is associated with reduced OCS use in patients treated in a real-world setting, potentially mitigating adverse health sequelae caused by OCS use in these patients.Food allergy is often understood as an IgE-mediated hypersensitivity, characterized by allergic symptoms which occur "immediately" after the ingestion of a relevant food allergen. Increasingly, however, other food-related immune-mediated disorders are recognized in which symptoms can have a delayed onset and IgE does not play a central role. One of the described examples of the latter is eosinophilic esophagitis (EoE) - a disease defined pathologically by local eosinophilic inflammation in the esophagus in the setting of symptoms of esophageal dysfunction. The evidence that EoE is a food-mediated allergic disease includes i) almost all patients respond to an elemental diet and many respond to a diet in which dairy, wheat, eggs and/or soy are eliminated, ii) the presence of food-specific IgE and Th2 cells are consistent with a loss of tolerance to trigger foods and iii) many EoE patients have concomitant IgE-mediated food allergy and other allergic co-morbidities. This narrative review focuses on the hypothesis that EoE is a form of chronic food allergy. The goal is to describe similarities and differences in EoE and IgE-mediated food allergy, and to consider ways that these two increasingly common forms of food allergy are related to each other.

Osteoarthritis causes a progressive deterioration to the protective cartilage between the joints leading to chronic pain and disability. This review focuses on the intrinsic potential of MSCs to stabilize and repair the cartilage tissue of the knee joint in knee osteoarthritis (KOA) patients.

An online search through the PubMed database was conducted, limiting the search to the English language and human clinical trials within the past 5 years. Twenty-one clinical trials passed the inclusion criteria. Combined, those trials involved the participation of 589 patients where the progress of the treatments was monitored between a 4-month to 7-years period. The cartilage volume and defects were observed through an MRI to provide an objective assessment. While the pain and knee function were monitored using KOOS, VAS, and WOMAC scoring scales providing a subjective assessment.

MRI scans obtained from clinical trials demonstrate a slowed progression of cartilage degeneration and early signs of cartilage regeneration in KOA patients at the 12-month follow-up period. No major adverse effects were observed post-intervention. The overall KOOS, WOMAC, and VAS scores in patients receiving MSC treatment were reduced, suggesting subjective improvements in knee function and pain reduction when compared to patients in the placebo group.

The use of MSC therapy is a valid form of treatment for KOA as it targets the disease itself rather than the symptoms. We found MSC therapy in KOA patients to be safe, effective, and feasible in its execution.

The use of MSC therapy is a valid form of treatment for KOA as it targets the disease itself rather than the symptoms. We found MSC therapy in KOA patients to be safe, effective, and feasible in its execution.

Although lots of long non-coding RNAs (lncRNAs) have been demonstrated to be involved in carcinogenesis, the functions of numerous of lncRNAs remain unknown. Bioinformatics online database showed that lncRNA LOC100132707 was highly expressed in metastatic melanoma tissues, and its expression predicted a lower overall survival rate in melanoma patients. However, LOC100132707 function in uveal melanoma (UM) progression still remains unclear. In the present study, we aimed to elucidate the role and molecular mechanisms underlying LOC100132707 in UM.

RT-PCR was used to detect the levels of LOC100132707 in UM cells. Cell migration, invasion and tumorigenesis were tested by using the transwell chamber assay and in vivo assay.

LOC100132707 expression in metastatic UM cell line MM28 was significantly higher than that of the non-metastatic UM cell lines, MP38, MP46 and MP65, as well as the expressions of LOC100132707-related genes, including XRN1, PARP14, JAK2, DDX60, BUB1 and SAMD9L. LOC100132707 downregulation significantly repressed cell migration and invasion abilities, whereas overexpressing JAK2 rescued these effects. Consistently, upregulation of LOC100132707 induced significant increases in cell migration and invasion abilities via upregulating JAK2. In addition, silencing of LOC100132707 significantly repressed the in vivo tumor formation ability in UM cells.

This study reveals that silence of LOC100132707 represses the migration of UM via downregulating JAK2. The LOC100132707/JAK2 axis might serve as a potent target for the prevention and treatment of UM metastasis.

This study reveals that silence of LOC100132707 represses the migration of UM via downregulating JAK2. The LOC100132707/JAK2 axis might serve as a potent target for the prevention and treatment of UM metastasis.

At present, there is a lack of precise knowledge on acute myeloid leukemia (AML) at the molecular level, and understanding its occurrence at the genetic level is conducive to the development of targeted therapies. Therefore, in this study the relationship between the lncRNA

-miR183-5p-FOXO1 axis and AML was explored.

Expression of lncRNA

and miR183-5p was quantified by quantitative real-time PCR, and the level of FOXO1 and other proteins was measured by Western blot. Expression vectors of lncRNA

, miR183-5p, and FOXO1 were constructed to assess effects of the three on cell proliferation and apoptosis. MTT reduction assays were employed for cell proliferation, flow cytometry for cell cycle and apoptosis, and dual luciferase-reporter assays for the targeting relationship between lncRNA

and miR183-5p and miR183-5p and FOXO1.

lncRNA

was highly expressed in peripheral blood/leukemia cell lines of patients with AML compared with normal human peripheral blood/peripheral blood mononuclear cells. miR183-5p was the target of lncRNA

and

the target gene of miR183-5p rather than lncRNA SNHG16. Absence of lncRNA

led to upregulation of miR183-5p, promotion of apoptosis, and inhibition of proliferation. Suppression of miR183-5p accelerated cell proliferation and hindered apoptosis. miR183-5p negatively regulated FOXO1, and FOXO1 promoted proliferation and inhibited apoptosis. Inhibition of miR183-5p counteracted the changes caused by lncRNA

absence.

lncRNA

regulates the progress of AML via the miR183-5p-FOXO1 axis.

lncRNA SNHG16 regulates the progress of AML via the miR183-5p-FOXO1 axis.

The zinc finger protein, ZBTB48, is a telomere-associated protein. It was renamed as telomeric zinc finger-associated protein (TZAP) binding to elongated telomeres. However, its expression level was not measured in cancers.

We analyzed TZAP mRNA levels in 60 colorectal cancers (CRC) and its correlation with telomere length and TERT was studied.

TZAP mRNA in CRC was higher statistically than that in paired non-cancerous tissues (p = 0.033). Higher TZAP was found in carcinoembryonic antigen (CEA)-positive CRCs (>5 ng/mL) (p = 0.012). Shorter telomere was found in CRCs with high TZAP expression than that with low TZAP expression (p = 0.010). According to quantitative correlation analysis, TZAP has a correlation with age (

= -0.349, p = 0.007), TERT (

= 0.279, p = 0.041) and telomere length (

= -0.305, p = 0.021). TZAP expression did not harbor prognostic value in CRC. Inhibition of TZAP expression by siRNA suppresses cell growth in HT29 cells; however, it resulted in increased cell viability in HCT116 cells. TZAP inhibition induces a decrease in mRNA levels of TERT in both HT29 and HCT116 cells. TCGA data analysis showed higher expression of TZAP showed poorer overall survival in colon cancer (p = 0.001); however, it did not have a significance in rectal cancer (p = 0.951).

We suggested that TZAP may be a possible biomarker for CRC.

We suggested that TZAP may be a possible biomarker for CRC.

Previous reports showed that

was associated with several cancers but the function of

in cervical cancer was unknown. This study aimed to investigate the clinical effect and function of

in cervical cancer.

In this study, the relative expression of

in cervical cancer was detected by RT-qPCR. In order to determine the cell proliferation and migration and invading ability and apoptosis more accurately, we used CCK8 assay, Edu assay, wound healing assay, migration and invasion assay, flow cytometry assay, co-immunoprecipitation, proteomics and Western blot by silencing and overexpressing

, respectively. The role of

on tumor progression was explored in vitro and vivo.

The relative expression of

in cervical cancer tissues was up-regulated (P<0.05). In cervical cancer cell lines, silencing of

restrained cell progression and EMT, while over-expression of

accelerated cell progression and EMT in vivo and vitro (P<0.05).

acts as an oncogene in cervical cancers and knockdown of

inhibited cervical cancer cells growth in vitro and in vivo. There is a close relationship between the relative expression of

and clinical outcome in cervical cancer patients.

APOC1 acts as an oncogene in cervical cancers and knockdown of APOC1 inhibited cervical cancer cells growth in vitro and in vivo. There is a close relationship between the relative expression of APOC1 and clinical outcome in cervical cancer patients.