Notes

Prenatal phthalate coverage along with early on the child years wheeze from the SELMA study.
These biological effects were found to be mediated by the AKT and MAPK signalling pathways.

Altogether, this study demonstrates that YWHAE is substantially upregulated in ovarian cancer tissues, representing a risk factor for the prognosis of ovarian cancer that is positively correlated with HE4 expression. Furthermore, YWHAE and its downstream pathways may represent new therapeutic targets for ovarian cancer.
Altogether, this study demonstrates that YWHAE is substantially upregulated in ovarian cancer tissues, representing a risk factor for the prognosis of ovarian cancer that is positively correlated with HE4 expression. Furthermore, YWHAE and its downstream pathways may represent new therapeutic targets for ovarian cancer.
Extracorporeal shock wave therapy (ESWT) has been used for various pathologies associated with bone marrow oedema (BME). However, it is still not clear whether ESWT may be favourable in the treatment of BME. C188-9 clinical trial Therefore, the aim of this systematic review was to assess the efficacy of ESWT for the treatment of BME.

MEDLINE was searched for relevant literature with no time constraints. Both randomized and non-randomized trials were included. Case reports and conference abstracts were excluded. Titles and abstracts were screened and full-text articles of included studies were retrieved. Data on the effect of ESWT on pain, function, and the BME area on magnet resonance imaging were extracted.

Pain, function, and magnet resonance imaging results all improved across the studies - regardless of whether it was a randomized or non-randomized study. This effect was consistent across multiple pathologies such as osteonecrosis of the femoral head, BME associated with knee osteoarthritis, Kienböck's disease, and osteitis pubis. The meta-analysis showed that pain (after 1 month weighted mean difference (WMD) = - 2.23, 95% CI - 2.58 to - 1.88, P < 0.0001; after 3-6 month WMD = - 1.72, 95% CI - 2.52 to - 0.92, P < 0.00001) and function (after 1 month WMD = - 1.59, 95% CI - 2.04 to - 1.14, P < 0.0001; after 3-6 month WMD = - 2.06, 95% CI - 3.16 to - 0.96, P = 0.0002; after ≥ 12 month WMD = - 1.20, 95% CI - 1.83 to - 0.56, P = 0.0002) was reduced in terms of ESWT treatment compared to a control group.

Based on the available evidence, ESWT may be an adequate option for conservative therapy in pathologies involving BME.

PROSPERO, CRD42021201719 . Registered 23 December 2020.
PROSPERO, CRD42021201719 . Registered 23 December 2020.
Variants identified through parent-child trio-WES yield up to 28-55% positive diagnostic rate across a variety of Mendelian disorders, there remain numerous patients who do not receive a genetic diagnosis. Studies showed that some aberrant splicing variants, which are either not readily detectable by WES or could be miss-interpreted by regular detecting pipelines, are highly relevant to human diseases.

We retrospectively investigated the negative molecular diagnostics through trio-WES for 15 genetically undiagnosed patients whose clinical manifestations were highly suspected to be genetic disorders with well-established genotype-phenotype relationships. We scrutinized the synonymous variants from WES data and Sanger sequenced the suspected intronic region for deep intronic variants. The functional consequences of variants were analyzed by in vitro minigene experiments.

Here, we report two abnormal splicing events, one of which caused exon truncating due to the activation of cryptic splicing site by a synonymous variant; the other caused partial intron retention due to the generation of splicing sites by a deep intronic variant.

We suggest that, despite initial negative genetic test results in clinically highly suspected genetic diseases, the combination of predictive bioinformatics and functional analysis should be considered to unveil the genetic etiology of undiagnosed rare diseases.
We suggest that, despite initial negative genetic test results in clinically highly suspected genetic diseases, the combination of predictive bioinformatics and functional analysis should be considered to unveil the genetic etiology of undiagnosed rare diseases.
In recent years, the use of ferritins as nano-vehicles for drug delivery is taking center stage. Compared to other similar nanocarriers, Archaeoglobus fulgidus ferritin is particularly interesting due to its unique ability to assemble-disassemble under very mild conditions. Recently this ferritin was engineered to get a chimeric protein targeted to human CD71 receptor, typically overexpressed in cancer cells.

Archaeoglobus fulgidus chimeric ferritin was used to generate a self-assembling hybrid nanoparticle hosting an aminic dendrimer together with a small nucleic acid. The positively charged dendrimer can indeed establish electrostatic interactions with the chimeric ferritin internal surface, allowing the formation of a protein-dendrimer binary system. The 4 large triangular openings on the ferritin shell represent a gate for negatively charged small RNAs, which access the internal cavity attracted by the dense positive charge of the dendrimer. This ternary protein-dendrimer-RNA system is efficiently uptaken by acute myeloid leukemia cells, typically difficult to transfect. As a proof of concept, we used a microRNA whose cellular delivery and induced phenotypic effects can be easily detected. In this article we have demonstrated that this hybrid nanoparticle successfully delivers a pre-miRNA to leukemia cells. Once delivered, the nucleic acid is released into the cytosol and processed to mature miRNA, thus eliciting phenotypic effects and morphological changes similar to the initial stages of granulocyte differentiation.

The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells.
The results here presented pave the way for the design of a new family of protein-based transfecting agents that can specifically target a wide range of diseased cells.
The Hydra head organizer acts as a signaling center that initiates and maintains the primary body axis in steady state polyps and during budding or regeneration. Wnt/beta-Catenin signaling functions as a primary cue controlling this process, but how Wnt ligand activity is locally restricted at the protein level is poorly understood. Here we report a proteomic analysis of Hydra head tissue leading to the identification of an astacin family proteinase as a Wnt processing factor.

Hydra astacin-7 (HAS-7) is expressed from gland cells as an apical-distal gradient in the body column, peaking close beneath the tentacle zone. HAS-7 siRNA knockdown abrogates HyWnt3 proteolysis in the head tissue and induces a robust double axis phenotype, which is rescued by simultaneous HyWnt3 knockdown. Accordingly, double axes are also observed in conditions of increased Wnt activity as in transgenic actinHyWnt3 and HyDkk1/2/4 siRNA treated animals. HyWnt3-induced double axes in Xenopus embryos could be rescued by coinjection of HAS-7 mRNA.
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