Designing novel Au(III) complexes based on the structure of diazepam: Achieving a multiaction mechanism against glioma.

Metal-based drugs have been used in the clinical treatment of tumors for over 30 years. However, no metal-based drugs have been clinically approved to treat glioma. Although metal complexes have excellent cytotoxicity, their most critical problem is crossing the blood-brain barrier.

Loading polyaniline (PANI) nanoparticles to mesoporous hydroxyapatite (HAp) spheres for near infrared (NIR) induced doxorubicin (DOX) drug delivery and colon cancer treatment.

In response to the pressing need for more efficient and targeted cancer therapies, this study presents the development of biodegradable hydroxyapatite/polyaniline (HAp/PANI) nanocomposite drug carriers for near-infrared (NIR)-induced drug delivery. The synthesis involved loading polyaniline onto mesoporous hydroxyapatite spheres, resulting in high drug loading capacity and tunable NIR responsiveness. The HAp/PANI spheres exhibited superior photothermal properties compared to pristine HAp under NIR irradiation, along with excellent biocompatibility.

Prognostic and immunological significance of metastasis-associated protein 3 in patients with thymic epithelial tumors.

Background: Immune checkpoint inhibitors have shown promising anticancer activity and have recently been proposed as a therapy for thymic epithelial tumors (TETs); however, this treatment is only effective for a subgroup of TET patients. Thus, this study aims to identify the potential genes implicated in the regulation of cancer immunity in TETs.

Methods: The TETs RNA-seq and clinical data were obtained from The Cancer Genome Atlas (TCGA) database.

CRL4 E3 ubiquitin ligase targets MeCP2 for degradation to prevent DNA hypermethylation and ensure normal transcription in growing oocytes.

The DNA methylation is gradually acquired during oogenesis, a process sustained by successful follicle development. However, the functional roles of methyl-CpG-binding protein 2 (MeCP2), an epigenetic regulator displaying specifical binding with methylated DNA, remains unknown in oogenesis. In this study, we found MeCP2 protein was highly expressed in primordial and primary follicle, but was almost undetectable in secondary follicles.

Development of Anticancer Ferric Complex Based on Human Serum Albumin Nanoparticles That Generate Oxygen in Cells to Overcome Hypoxia-Induced Resistance in Metal Chemotherapy.

To achieve the remarkable therapeutic efficacy of a ferric (Fe) complex via a reactive oxygen species (ROS) mechanism in solid tumors, a therapeutic Fe-based Schiff-base complex () was synthesized and encapsulated in human serum albumin (HSA) nanoparticles (NPs), which generated oxygen (O) in cancer cells in situ. The NP () delivery system effectively overcame hypoxia-induced resistance in metal chemotherapy, alleviated the hypoxic condition of tumor tissues, and showed excellent tumor suppression by generating excess ROS and promoting the apoptosis of SK-N-MC tumor cells. The not only enhanced the ability of the complex to target tumor cells but also decreased adverse effects in vivo.

Role of Ubiquitin-specific Proteases in Hepatocellular Carcinoma Pathogenesis.

Signaling pathways in hepatocellular carcinoma are primarily mediated by the phosphorylation and ubiquitination of post-translational proteins. In mammalian cells, ubiquitin-specific proteases (USPs) account for the majority of protein deubiquitination activities. In addition to transcriptional and post-translational regulation, ubiquitination plays an important role in the regulation of key proteins.

The EZH2-H3K27me3 axis modulates aberrant transcription and apoptosis in cyclophosphamide-induced ovarian granulosa cell injury.

Chemotherapy-induced ovarian damage and infertility are significant concerns for women of childbearing age with cancer; however, the underlying mechanisms are still not fully understood. Our study has revealed a close association between epigenetic regulation and cyclophosphamide (CTX)-induced ovarian damage. Specifically, CTX and its active metabolite 4-hydroperoxy cyclophosphamide (4-HC) were found to increase the apoptosis of granulosa cells (GCs) by reducing EZH2 and H3K27me3 levels, both in vivo and in vitro.

KDM2A Deficiency in the Liver Promotes Abnormal Liver Function and Potential Liver Damage.

Dysregulation of metabolic functions in the liver impacts the development of diabetes and metabolic disorders. Normal liver function can be compromised by increased inflammation via the activation of signaling such as nuclear factor (NF)-κB signaling. Notably, we have previously identified lysine demethylase 2A (KDM2A)-as a critical negative regulator of NF-κB.

Clinical outcomes of frozen-thawed blastocysts from zygotes with no or one pronucleus for in vitro fertilization and intracytoplasmic sperm injection cycles.

Purpose: To investigate the clinical outcomes of in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) cycles using frozen-thawed blastocyst transfers derived from zygotes with no (0PN) or one pronucleus (1PN).

Methods: This retrospective study included 7084 0PN, 2238 1PN, and 72,266 two pronuclear (2PN) embryos cultured to the blastocyst stage from 19,631 IVF and 12,377 ICSI cycles between March 2018 and December 2021. Developmental potential and clinical outcomes of 0PN, 1PN, and 2PN embryos were analyzed.

Benzo[]quinoxaline-Based Complexes [Ir(pbt)(dppn)]Cl and [Ir(pt)(dppn)]Cl: Modulation of Photo-Oxidation Activity and Light-Controlled Luminescence.

Based on benzo[]dipyrido[3,2-a:2',3'-]phenazine (dppn) with photo-oxidation activity, complexes [Ir(pbt)(dppn)]Cl () and [Ir(pt)(dppn)]Cl () have been synthesized (pbtH = 2-phenylbenzothiazole, and ptH = 2-phenylthiazole), with two aims, including studying the influence of the cyclometalating ligands (pbt in , pt in ) on the photo-oxidation activity of these complexes and exploring their photo-oxidation-induced luminescence. Both H nuclear magnetic resonance (NMR) and electrospray (ES) mass spectrometry indicate that the benzo[]quinoxaline moiety in complex can be oxidized at room temperature upon irradiation with 415 nm light. Thus, this complex in CHCl shows photo-oxidation-induced turn-on yellow luminescence.

Encapsulation of Au(III) Complex Using Lactoferrin Nanoparticles to Combat Glioma.

Metal-based drugs have been used for decades to treat solid cancers; however, these drugs have no significant therapeutic effect on glioma because they cannot effectively cross the blood-brain barrier (BBB). To develop a novel metal-based agent that can cross the BBB to target glioma, we synthesized an Au complex (C2) with remarkable glioma cytotoxicity and fabricated lactoferrin (LF)-C2 nanoparticles (LF-C2 NPs) as a novel therapy. We confirmed that C2 kills glioma cells by inducing apoptosis and autophagic death.

Cracking the code: Deciphering the role of the tumor microenvironment in osteosarcoma metastasis.

Osteosarcoma (OS) is the most common malignant bone tumor in children and adolescents. It is characterized by a rapid progression, poor prognosis, and early pulmonary metastasis. Over the past 30 years, approximately 85% of patients with osteosarcoma have experienced metastasis.

Ovulatory signal-triggered chromatin remodeling in ovarian granulosa cells by HDAC2 phosphorylation activation-mediated histone deacetylation.

Background: Epigenetic reprogramming is involved in luteinizing hormone (LH)-induced ovulation; however, the underlying mechanisms are largely unknown.

Results: We here observed a rapid histone deacetylation process between two waves of active transcription mediated by the follicle-stimulating hormone (FSH) and the LH congener human chorionic gonadotropin (hCG), respectively. Analysis of the genome-wide H3K27Ac distribution in hCG-treated granulosa cells revealed that a rapid wave of genome-wide histone deacetylation remodels the chromatin, followed by the establishment of specific histone acetylation for ovulation.

Inhibition of PRMT5 by market drugs as a novel cancer therapeutic avenue.

Market drugs, such as Food and Drug Administration (FDA) or European Medicines Agency (EMA)-approved drugs for specific indications provide opportunities for repurposing for newer therapeutics. This potentially saves resources invested in clinical trials that verify drug safety and tolerance in humans prior to alternative indication approval. Protein arginine methyltransferase 5 (PRMT5) overexpression has been linked to promoting the tumor phenotype in several cancers, including pancreatic ductal adenocarcinoma (PDAC), colorectal cancer (CRC), and breast cancer (BC), making PRMT5 an important target for cancer therapy.

HucMSC-EVs Facilitate In Vitro Development of Maternally Aged Preantral Follicles and Oocytes.

Follicle developmental capacity and oocyte quality decline with advanced maternal age. Extracellular vesicles from human umbilical cord mesenchymal stem cells (HucMSC-EVs) act as a potential therapeutic product in the treatment of age-related ovarian dysfunction. In vitro culture (IVC) of preantral follicles is a useful method for understanding the mechanism of follicle development and is a promising means for improving female fertility.

Combined effects of vitamin D and neferine on the progression and metastasis of colorectal cancer.

Purpose: To investigate the synergistic effect of vitamin D and neferine on the growth and metastasis of colorectal cancer (CRC).

Methods: The synergistic effect of biologically active form of vitamin D, VD and neferine on the treatment of CRC was investigated by bliss analysis. Colony formation and wound healing ability, migration and invasion ability, and epithelial mesenchymal transition of HCT-116 cells, as a response to the combination treatment with VD and neferine were evaluated.

Decreased histidine-rich glycoprotein and increased complement C4-B protein levels in follicular fluid predict the IVF outcomes of recurrent spontaneous abortion.

Background: Recurrent spontaneous abortion (RSA) is a common and complicated pregnancy-related disease that lacks a suitable biomarker to predict its recrudescence.

Methods: Tandem mass tag (TMT) analysis was conducted to obtain quantitative proteomic profiles in follicular fluid from patients with a history of RSA and from control group. ELISA validation of candidate differentially expressed proteins was conducted in a larger group of patients.

Role of siderophore in Pseudomonas fluorescens biofilm formation and spoilage potential function.

We investigated the function of pyoverdine in the biofilm formation, motility, and spoilage potential of Pseudomonas fluorescens. We targeted and identified two major genes (pvdA and pvdE) that are involved in the biosynthesis of siderophores. We next constructed ΔpvdA and ΔpvdE mutants of P.

Organometallic gold(I) and gold(III) complexes for lung cancer treatment.

Metal compounds, especially gold complexes, have recently gained increasing attention as possible lung cancer therapeutics. Some gold complexes display not only excellent activity in cisplatin-sensitive lung cancer but also in cisplatin-resistant lung cancer, revealing promising prospects in the development of novel treatments for lung cancer. This review summarizes examples of anticancer gold(I) and gold (III) complexes for lung cancer treatment, including mechanisms of action and approaches adopted to improve their efficiency.

The role of IL-33/ST2 signaling in the tumor microenvironment and Treg immunotherapy.

Interleukin (IL)-33 is a tissue-derived nuclear cytokine belonging to the IL-1 family. Stimulation-2 (ST2) is the only known IL-33 receptor. ST2 signals mostly on immune cells found within tissues, such as regulatory T cells (Treg cells), CD8+ T cells, and natural killer (NK) cells.

Biallelic variants in MOS cause large polar body in oocyte and human female infertility.

Study Question: What is the genetic basis of female infertility involving abnormal oocyte morphology with the production of a large first polar body (PB1)?

Summary Answer: The homozygous missense variant (c.791C>G) and compound missense variants (c.596A>T and c.