PKD1 and PKD2 mRNA cis-inhibition drives polycystic kidney disease progression.

Autosomal dominant polycystic kidney disease (ADPKD), among the most common human genetic conditions and a frequent etiology of kidney failure, is primarily caused by heterozygous PKD1 mutations. Kidney cyst formation occurs when PKD1 dosage falls below a critical threshold. However, no framework exists to harness the remaining allele or reverse PKD1 decline.

Application of a Neisseria meningitidis antigen microarray to identify candidate vaccine proteins from a human Phase I clinical trial.

Meningococcal meningitis is a rare but serious condition affecting mainly children and young adults. Outer membrane vesicles (OMV) from Neisseria meningitidis have been used successfully as vaccines against the disease, although they only provide protection against a limited number of the many existing variants. There have been many attempts to identify suitable protein antigens for use in defined vaccines that provide broad protection against the disease, such as that leading to the development of the four component 4CMenB vaccine.

A methionine-Mettl3-N-methyladenosine axis promotes polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is a common monogenic disorder marked by numerous progressively enlarging kidney cysts. Mettl3, a methyltransferase that catalyzes the abundant N-methyladenosine (mA) RNA modification, is implicated in development, but its role in most diseases is unknown. Here, we show that Mettl3 and mA levels are increased in mouse and human ADPKD samples and that kidney-specific transgenic Mettl3 expression produces tubular cysts.

Anticancer Efficacy of Oral Docetaxel Nanoformulation for Metronomic Chemotherapy in Metastatic Lung Cancer.

Metronomic chemotherapy, giving low doses of chemotherapeutics (e.g., docetaxel) on a frequent schedule over a long time, may improve outcomes and reduce side effects for cancer patients.

Androgen Receptor Enhances the Efficacy of Sorafenib Against Hepatocellular Carcinoma Through Enriched EpCAM Stemness.

Background/aim: The role of androgen receptor (AR) in hepatocellular carcinoma (HCC) development is controversial. Therefore, the translational value of targeting AR in HCC is unknown. Sorafenib, a multiple kinase inhibitor, is the standard therapy for patients with unresectable HCC.

Histone lysine demethylase KDM4B regulates the alternative splicing of the androgen receptor in response to androgen deprivation.

Alternative splicing is emerging as an oncogenic mechanism. In prostate cancer, generation of constitutively active forms of androgen receptor (AR) variants including AR-V7 plays an important role in progression of castration-resistant prostate cancer (CRPC). AR-V7 is generated by alternative splicing that results in inclusion of cryptic exon CE3 and translation of truncated AR protein that lacks the ligand binding domain.

Immunogenicity profiling of protein antigens from capsular group B Neisseria meningitidis.

Outer membrane vesicle (OMV)- based vaccines have been used to provide strain-specific protection against capsular group B Neisseria meningitidis infections, but the full breadth of the immune response against the components of the OMV has not been established. Sera from adults vaccinated with an OMV vaccine were used to screen 91 outer membrane proteins (OMPs) incorporated in an antigen microarray panel. Antigen-specific IgG levels were quantified pre-vaccination, and after 12 and 18 weeks.

Cancer-targeted BikDD gene therapy elicits protective antitumor immunity against lung cancer.

Targeted cancer-specific gene therapy is a promising strategy for treating metastatic lung cancer, which is a leading cause of lung cancer-related deaths. Previously, we developed a cancer-targeted gene therapy expression system with high tumor specificity and strong activity that selectively induced lung cancer cell killing without affecting normal cells in immunocompromised mice. Here, we found this cancer-targeted gene therapy, SV-BikDD, composed of the survivin promoter in the VP16-GAL4-WPRE integrated systemic amplifier system to drive the apoptotic gene BikDD, not only caused cytotoxic effects in cancer cells but also elicited a cancer-specific cytotoxic T lymphocyte response to synergistically increase the therapeutic effect and further develop an effective systemic antitumoral immunity against rechallenges of tumorigenic dose of parental tumor cells inoculated at distant sites in immunocompetent mice.

Immunoproteomic identification of the hypothetical protein NMB1468 as a novel lipoprotein ubiquitous in Neisseria meningitidis with vaccine potential.

Many potential vaccine candidates for serogroup B Neisseria meningitidis (NMB) have been identified by reverse vaccinology, a genome-based approach. However, some candidates may be unseen owing to uncertain annotation or their peculiar properties. In this study, we describe the preparation and identification of a novel lipoprotein expressed in all meningococcal strains tested.