Regulated GATA1 expression as a universal gene therapy for Diamond-Blackfan anemia.

Gene therapy using hematopoietic stem and progenitor cells is altering the therapeutic landscape for patients with hematologic, immunologic, and metabolic disorders but has not yet been successfully developed for individuals with the bone marrow failure syndrome Diamond-Blackfan anemia (DBA). More than 30 mutations cause DBA through impaired ribosome function and lead to inefficient translation of the erythroid master regulator GATA1, providing a potential avenue for therapeutic intervention applicable to all patients with DBA, irrespective of the underlying genotype. Here, we report the development of a clinical-grade lentiviral gene therapy that achieves erythroid lineage-restricted expression of GATA1.

BMP suppresses Wnt signaling via the Bcl11b-regulated NuRD complex to maintain intestinal stem cells.

Lgr5 intestinal stem cells (ISCs) are crucial for the intestinal epithelium renewal and regeneration after injury. However, the mechanism underlying the interplay between Wnt and BMP signaling in this process is not fully understood. Here we report that Bcl11b, which is downregulated by BMP signaling, enhances Wnt signaling to maintain Lgr5 ISCs and thus promotes the regeneration of the intestinal epithelium upon injury.

METTL3 restricts RIPK1-dependent cell death via the ATF3-cFLIP axis in the intestinal epithelium.

Intestinal epithelial cells (IECs) are pivotal for maintaining intestinal homeostasis through self-renewal, proliferation, differentiation, and regulated cell death. While apoptosis and necroptosis are recognized as distinct pathways, their intricate interplay remains elusive. In this study, we report that Mettl3-mediated mA modification maintains intestinal homeostasis by impeding epithelial cell death.

A Network of Sporogenesis-Responsive Genes Regulates the Growth, Asexual Sporogenesis, Pathogenesis and Fusaric Acid Production of f. sp. .

The conidia produced by f. sp. (Foc), the causative agent of Fusarium Wilt of Banana (FWB), play central roles in the disease cycle, as the pathogen lacks a sexual reproduction process.

The Signal Peptidase FoSpc2 Is Required for Normal Growth, Conidiation, Virulence, Stress Response, and Regulation of Light Sensitivity in Fusarium odoratissimum.

Signal peptidase (SPase) is responsible for cleavage of N-terminal signal peptides in most secretory precursor proteins and many membrane proteins during maturation. In this study, we identified four components of the SPase complex (FoSec11, FoSpc1, FoSpc2, and FoSpc3) in the banana wilt fungal pathogen Fusarium odoratissimum. We proved that interactions exist among the four SPase subunits by bimolecular fluorescence complementation (BiFC) and affinity purification and mass spectrometry (AP-MS) assays.

Segregation of the stemness program from the proliferation program in intestinal stem cells.

Stem cells can undergo continuous self-renewal and meanwhile retain the stemness capability to differentiate to mature functional cells. However, it is unclear whether the proliferation property can be segregated from the stemness in stem cells. The intestinal epithelium undergoes fast renewal, and the Lgr5 intestinal stem cells (ISCs) are essential to maintain homeostasis.

One-Step Synthesis of Peptide-Gold Nanoclusters with Tunable Fluorescence and Enhanced Gene Delivery Efficiency.

In this study, peptide-gold nanoclusters with tunable fluorescence were prepared by a simple "one-pot" method, which were used for gene localization and delivery in vivo to achieve efficient intracellular colocalization, uptake, and transfection. The efficiency of pDNA transfection was up to 70.6%, and there was no obvious cytotoxicity.

ERR, a Novel Biomarker, Associates with Pathoglycemia of Endometrial Cancer to Predict Myometrial Invasion.

We aim to investigate the correlation between the expression of estrogen-related receptor (ERR) and endometrial cancer (EC) progression and to evaluate the potential of ERR as a new biomarker for EC diagnosis. We analyzed the ERR expression profile and the correlation with the corresponding clinical characteristics of EC samples from The Cancer Genome Atlas (TCGA), the Clinical Proteomic Tumor Analysis Consortium (CPTAC) databases, and the International Cancer Genome Consortium (ICGC) databases. Immunohistochemical (IHC) analysis was conducted on tissue samples, and enzyme linked immunosorbent assay (ELISA) was used in serum samples to detect the levels of ERR.

Self-assembly of peptide nanofibers with chirality-encoded antimicrobial activity.

The nanostructured antimicrobial agents, self-assembled by the antimicrobial peptides (AMPs), represent an intriguing platform for the treatment of pathogens. Although the structural characteristics significantly influence antimicrobial functionality, the role of chirality is usually ignored and still unclear. Herein, two homochiral AMPs (all L- or all D-amino acids), including C-VR (LL) and C-VR (DD), and a heterochiral AMP with alternating D-/L-amino acids, C-VR (DL), were self-assembled into left-handed, right-handed, and right-handed helical nanofibers, respectively.

ERRα inhibitor acts as a potential agonist of PPARγ to induce cell apoptosis and inhibit cell proliferation in endometrial cancer.

Two transcriptional factors, peroxisome proliferator-activated receptor-γ (PPARγ) and estrogen-related receptor-α (ERRα), have been reported to be key regulators of cellular energy metabolism. However, the relationship between ERRα and PPARγ in the development of endometrial cancer (EC) is still unclear. The expression levels of PPARγ and ERRα in EC were evaluated by quantitative real-time PCR, western blot, tissue array and immunohistochemistry.

Green fluorescent protein inspired fluorophores.

Green fluorescence proteins (GFP) are appealing to a variety of biomedical and biotechnology applications, such as protein fusion, subcellular localizations, cell visualization, protein-protein interaction, and genetically encoded sensors. To mimic the fluorescence of GFP, various compounds, such as GFP chromophores analogs, hydrogen bond-rich proteins, and aromatic peptidyl nanostructures that preclude free rotation of the aryl-alkene bond, have been developed to adapt them for a fantastic range of applications. Herein, we firstly summarize the structure and luminescent mechanism of GFP.

PGC-1α and ERRα in patients with endometrial cancer: a translational study for predicting myometrial invasion.

Background: PGC-1α and ERRα are closely related to tumor formation and progression. However, the mechanism underlying the involvement of PGC-1α/ERRα in regulating invasion and migration in endometrial cancer remains to be explored.

Results: Elevated levels of PGC-1α and ERRα were associated with advanced myometrial invasion, and PGC-1α and Vimentin expression was related to the depth of myometrial invasion in premenopausal endometrial cancer.

Bioinspired Fluorescent Peptidyl Nanoparticles with Rainbow Colors.

The growing enthusiasm to mimic the luminous properties of fluorescent proteins (FPs) has expanded to include the potential biomedical applications of FP analogues. We developed a series of non-fluorescent oligopeptides (Fc-(X); where X = F, Y, W, and H; = 1-3) that can aggregate into fluorescent nanoparticles with rainbow colors, termed the peptidyl rainbow kit (PRK). The PRK encompasses the full visible color spectrum, and its photoluminescent properties may have originated from aggregation-induced emission (AIE).

Dual targeting of estrogen receptor α and estrogen-related receptor α: a novel endocrine therapy for endometrial cancer.

Background: Endometrial cancer (EC) is a hormone dependent carcinoma that may involve complex molecular mechanisms. Endocrine therapy by blocking the estrogen and estrogen receptor α (ERα) has been effective in breast cancer, while it is still controversial in EC. Recently, estrogen-related receptor α (ERRα) was proven to be another endocrine therapy target.

Clinical analysis of neoadjuvant chemotherapy in patients with advanced vulvar cancer: A STROBE-compliant article.

To investigate the effect of neoadjuvant chemotherapy in patients with advanced vulvar cancer and to provide references for clinical treatment.Clinical and pathological data of 12 patients with advanced vulvar carcinoma were collected. The response and operability rates, adverse effects, and prognosis of neoadjuvant chemotherapy were retrospectively analyzed.

Novel endocrine therapeutic strategy in endometrial carcinoma targeting estrogen-related receptor α by XCT790 and siRNA.

Purpose: To explore the targeted therapy of estrogen-related receptor α (ERRα) in endometrial cancer (EC) cells and its potential mechanisms.

Methods: The mRNA and protein expression levels of ERRα and estrogen receptor α (ERα) were detected by qPCR and Western blotting in RL-952, AN3-CA, HEC-1A, and HEC-1B EC cell lines. After treatment with the ERRα-specific antagonist XCT790 or infection with lentivirus-mediated small interfering RNA (siRNA) targeting the ERRα (siRNA-ERRα), cell proliferation and apoptosis were evaluated by MTS assay and flow cytometry.

Safety, pharmacokinetics, and antiviral activity of the cyclophilin inhibitor NIM811 alone or in combination with pegylated interferon in HCV-infected patients receiving 14 days of therapy.

Background: Cyclophilin inhibitors have shown activity against a variety of viruses, including HCV. NIM811, a novel, non-immunosuppressive cyclophilin inhibitor was studied in ascending doses in a randomized, double-blind, placebo-controlled 14-day trial in genotype 1 HCV patients. Doses of 10 up to 600 mg were given orally once or twice daily as monotherapy (9:3 randomization of NIM811:placebo).