Upregulation of hepatic flavin-containing monooxygenase 3 by increased corticosterone via glucocorticoid receptor contributes to gestational diabetes mellitus.

Gestational diabetes mellitus (GDM) significantly increases the risk of various complications during pregnancy and elevates the lifelong susceptibility to metabolic disorders. Previous studies have indicated elevated cortisol levels in women with GDM, and hepatic flavin-containing monooxygenase 3 (FMO3) contributes to diabetes mellitus. However, the specific mechanism by which cortisol affects FMO3 and its roles in GDM remain unclear.

AZD5153 enhances the chemo-sensitivity of gemcitabine on pancreatic cancer cells in vitro and in vivo.

Background: Pancreatic cancer is a malignant disease with a poor prognosis. Gemcitabine (GEM), the first-line treatment drug, shows limited efficacy because of the notorious drug resistance of pancreatic cancer. Therefore, the development of sensitive drugs for pancreatic cancer is essential.

Anti-tumor efficacy of RAF/MEK inhibitor VS6766 in KRAS-mutated colorectal cancer cells.

Purpose: Colorectal cancer (CRC) ranks third among most prevalent cancers worldwide. KRAS is the most frequently (30-40%) mutated oncogene in CRC, which has been defined as an "undruggable" therapeutic target over the past four decades.

Methods: In this study, we applied four HT-29 cell lines, namely HT-29-wild-type (HT-29-WT), point-mutated HT-29-KRAS, HT-29-KRAS and HT-29-KRAS, in order to detect the efficiency of RAF-MEK inhibitor VS6766, the BRAF inhibitor PLX4720 was selected as the control.

Review Article: Drug-Induced Liver Injury Associated With Antibody-Based Therapies in Haematologic Malignancies.

Background: Drug-induced liver injury (DILI) is a leading cause of liver damage. It is especially prevalent in haematologic malignancies, complicating treatment regimens and posing a risk for severe outcomes such as acute liver failure. Antibody-based therapies have significantly improved treatment outcomes.

Discovery of a New and Selective HPK1 PROTAC for Enhancing Tumor Immunotherapy through Eliminating GLK Degradation.

HPK1 is an attractive therapeutic target for tumor immunotherapy. Nevertheless, the formidable challenge selectivity over GLK and limited antitumor efficacy of HPK1 inhibitors and PROTACs impeded their developments. Here, we demonstrated that blocking GLK alone or simultaneous blocking both GLK and HPK1 could reduce immune activation through siRNA, which underscores the necessity for designing selective HPK1 degraders.

Multiplexed imaging mass cytometry elicits p-S6 as a therapeutic and prognostic factor in diffuse large B-cell lymphoma.

Diffuse large B-cell lymphoma (DLBCL) is a heterogeneous disease characterized by distinct morphological, genetic, and clinical features. DLBCL with Myc/Bcl-2 double expression (DE) has been positively correlated with poor prognosis and a low response rate to chemotherapy. However, molecular mechanisms underlying the malignant progression of DE DLBCL and the tumor microenvironment of DE DLBCL have not been fully elucidated.

Neutrophil-Mediated Tumor Discrimination Biomimetic Nanodevice for Precise Tumor Eradication and Metastasis Cascade Perturbing.

The deficient discrimination of tumor cells, limited accumulation of therapeutic agents in tumor foci, and undesirable tumor metastasis result in compromised therapeutic efficacy in antitumor therapy. Neutrophils, the most abundant circulating leukocytes, are key players in tumor progression and have a high affinity to tumors. Herein, a biomimetic tumor discrimination nanodevice (NL-FSB) is developed by harboring a pH-sensitive Fenton agent (FSB) in an activated neutrophil membrane-incorporated liposome for tumor-specific ablation.

Milciclib-mediated CDK2 inhibition to boost radiotherapy sensitivity in colorectal cancer.

Background: Colorectal cancer (CRC) ranks as the third most common cancer globally. Neoadjuvant radiotherapy is the standard treatment for locally advanced rectal cancer; however, primary or acquired resistance often leads to treatment failure. Identifying new targets to overcome radiotherapy resistance in CRC is crucial for improving patient outcomes.

Ubiquitination regulation of mitochondrial homeostasis: a new sight for the treatment of gastrointestinal tumors.

Mitochondrial homeostasis (MH) refers to the dynamic balance of mitochondrial number, function, and quality within cells. Maintaining MH is significant in the occurrence, development, and clinical treatment of Gastrointestinal (GI) tumors. Ubiquitination, as an important post-translational modification mechanism of proteins, plays a central role in the regulation of MH.

The neuroscience in breast cancer: Current insights and clinical opportunities.

The involvement of nerves in the development of breast cancer has emerged as a significant factor. Interaction between the nervous system and breast cancer can influence tumor initiation, growth, invasion, metastasis, reverse resistance to drugs, promote inflammation in tumors, and impair the immune system's ability to combat cancer. This review examined the intricate relationship linking the nervous system with breast cancer, emphasizing both central and peripheral aspects of the nervous system.

Vortioxetine exhibits anti-glioblastoma activity via the PI3K-Akt signaling pathway.

Glioblastoma multiforme (GBM) presents a significant challenge in oncology due to its highly aggressive nature and inherent resistance to conventional therapeutic interventions. Vortioxetine, a novel antidepressant, exhibits anticancer abilities and can traverse the blood-brain barrier. In this study, the antitumor effect and mechanism of vortioxetine on GBM cells were investigated.

Real-world Plasma Exposure of Nirmatrelvir/Ritonavir in Chinese Hospitalized Patients With COVID-19: A Multicenter Retrospective Study.

Background: Nirmatrelvir/ritonavir is licensed for the treatment of mild-to-moderate coronavirus disease (COVID-19) in patients at an increased risk of progression to severe disease. However, data on the real-world plasma exposure to nirmatrelvir/ritonavir remain limited, particularly in Chinese patients. This study aimed to assess the nirmatrelvir/ritonavir trough concentration (Ctrough) and identify its critical factors in hospitalized Chinese patients treated with nirmatrelvir/ritonavir 300 mg/100 mg twice daily over a 5-day course.

Epigenetic Regulation of Stromal and Immune Cells and Therapeutic Targets in the Tumor Microenvironment.

The tumor microenvironment (TME) plays a pivotal role in neoplastic initiation and progression. Epigenetic machinery, governing the expression of core oncogenes and tumor suppressor genes in transformed cells, significantly contributes to tumor development at both primary and distant sites. Recent studies have illuminated how epigenetic mechanisms integrate external cues and downstream signals, altering the phenotype of stromal cells and immune cells.

Auto-RapTAC: A Versatile and Sustainable Platform for the Automated Rapid Synthesis and Evaluation of PROTAC.

The tedious synthesis and limited throughput biological evaluation remain a great challenge for discovering new proteolysis targeting chimera (PROTAC). To rapidly identify potential PROTAC lead compounds, we report a platform named Auto-RapTAC. Based on the modular characteristic of the PROTAC molecule, a streamlined workflow that integrates lab automation with "click chemistry" joint building-block libraries was constructed.

Guidance Documents for Off-Label Drug Use Management for Chinese Health Care Institutions: A Scoping Review.

Background: Off-label drug use (OLDU) is a common practice in health care institutions, and numerous guidance documents have been developed to guide the management of OLDU in China. This scoping review aims to compare these documents and identify existing issues.

Methods: PubMed, EMbase, three Chinese databases, the National Public Service Platform for Standards Information and the official websites of pharmaceutical-related associations were searched to identify guidance documents relevant to the management of OLDU for Chinese health care institutions.

Review on the role of autophagy in the toxicity of nanoparticles and the signaling pathways involved.

As the development of nanotechnology, the application of nanoproducts and the advancement of nanomedicine, the contact of nanoparticles (NPs) with human body is becoming increasingly prevalent. This escalation elevates the risk of NPs exposure for workers, consumers, researchers, and both aquatic and terrestrial organisms throughout the production, usage, and disposal stages. Consequently, evaluating nanotoxicity remains critically important, though standardized assessment criteria are still lacking.

Structure-based identification of new orally bioavailable BRD9-PROTACs for treating acute myelocytic leukemia.

BRD9 is essential in regulating gene transcription and chromatin remodeling, and blocking BRD9 profoundly affects the survival of AML cells. However, the inhibitors of BRD9 suffer from various drawbacks, including poor phenotype and selectivity, and BRD9 PROTACs still face the challenge of druggability, which limits the development of blocking BRD9 in AML. This study described an oral activity BRD9 PROTAC C6 by recruiting the highly efficient E3 ligase.

Wee1 inhibitor PD0166285 sensitized TP53 mutant lung squamous cell carcinoma to cisplatin via STAT1.

Background: Lung squamous cell carcinoma (LUSCs) is associated with high mortality (20-30%) and lacks of effective treatments. Almost all LUSC exhibit somatic mutations in TP53. Wee1, a tyrosine kinase, regulates the cell cycle at the G2/M checkpoint.

Recent progress of ferroptosis in cancers and drug discovery.

Ferroptosis is a nonapoptotic form of cell death characterized by iron dependence and lipid peroxidation. Ferroptosis is involved in a range of pathological processes, such as cancer. Many studies have confirmed that ferroptosis plays an essential role in inhibiting cancer cell proliferation.

Hepatotoxicity of epidermal growth factor receptor - tyrosine kinase inhibitors (EGFR-TKIs).

Drug-induced liver injury (DILI) is one of the most frequently adverse reactions in clinical drug use, usually caused by drugs or herbal compounds. Compared with other populations, cancer patients are more prone to abnormal liver function due to primary or secondary liver malignant tumor, radiation-induced liver injury and other reasons, making potential adverse reactions from liver damage caused by anticancer drugs of particular concernduring clinical treatment process. In recent years, the application of epidermal growth factor receptor tyrosine kinase inhibitors (EGFR-TKIs) has changed the treatment status of a series of solid malignant tumors.

Tetrahydrocurcumin Attenuates Polymyxin B Sulfate-Induced HK-2 Cells Apoptosis by Inhibiting Endoplasmic Reticulum Stress-Mediated PERK/eIF2α/ATF4/CHOP Signaling Pathway Axis.

The clinical application of polymyxin B (PMB) is limited by its nephrotoxic effects, making the reduction of PMB-induced nephrotoxicity has become a pressing concern for clinicians. Tetrahydrocurcumin (THC), known for its beneficial characteristics in biological functions, presents an attractive option for intervention therapy to mitigate PMB-induced nephrotoxicity. However, the underlying mechanism of how THC mitigates PMB-induced nephrotoxicity is still poorly understood.