METTL14 suppresses the expression of YAP1 and the stemness of triple-negative breast cancer.

Background: Triple-negative breast cancer (TNBC) has pronounced stemness that is associated with relapse. N-methyladenosine (mA) plays a crucial role in shaping cellular behavior by modulating transcript expression. However, the role of mA in TNBC stemness, as well as the mechanisms governing its abundance, has yet to be elucidated.

Tanshinone IIA acts as a regulator of lipogenesis to overcome osimertinib acquired resistance in lung cancer.

Osimertinib is a novel epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI), acting as the first-line medicine for advanced EGFR-mutated NSCLC. Recently, the acquired resistance to osimertinib brings great challenges to the advanced treatment. Therefore, it is in urgent need to find effective strategy to overcome osimertinib acquired resistance.

Smoking and tetramer tryptase accelerate intervertebral disc degeneration by inducing METTL14-mediated DIXDC1 m modification.

Although cigarette smoking (CS) and low back pain (LBP) are common worldwide, their correlations and the mechanisms of action remain unclear. We have shown that excessive activation of mast cells (MCs) and their proteases play key roles in CS-associated diseases, like asthma, chronic obstructive pulmonary disease (COPD), blood coagulation, and lung cancer. Previous studies have also shown that MCs and their proteases induce degenerative musculoskeletal disease.

Single-Cell Transcriptome Profiling Reveals Multicellular Ecosystem of Nucleus Pulposus during Degeneration Progression.

Although degeneration of the nucleus pulposus (NP) is a major contributor to intervertebral disc degeneration (IVDD) and low back pain, the underlying molecular complexity and cellular heterogeneity remain poorly understood. Here, a comprehensive single-cell resolution transcript landscape of human NP is reported. Six novel human NP cells (NPCs) populations are identified by their distinct molecular signatures.

THOC2 and THOC5 Regulate Stemness and Radioresistance in Triple-Negative Breast Cancer.

Triple-negative breast cancer (TNBC) is the most aggressive subtype of breast cancer. Radioresistance and stemness are substantial obstacles to TNBC treatment. The THO complex (THOC) is a subunit of the TRanscription-EXport complex that functions in the coupling of transcription to nascent RNA splicing, elongation, and export.

Immunotherapy for triple-negative breast cancer: A molecular insight into the microenvironment, treatment, and resistance.

Clinicians have very limited options to treat triple-negative breast cancer (TNBC) due to the lack of effective targeted drugs. Recently, the findings of the mechanism underlying tumor-intrinsic immune escape have fueled a wave of studies into immunotherapy in breast cancer (BC). Compared with other BC subtypes, TNBC shows a better response to immunotherapy due to the higher level of tumor mutation burden and lymphocyte infiltration.

Activation of the eIF2α/ATF4 axis drives triple-negative breast cancer radioresistance by promoting glutathione biosynthesis.

Triple-negative breast cancer (TNBC) is the most aggressive breast cancer subtype. Radiotherapy is an effective option for the treatment of TNBC; however, acquired radioresistance is a major challenge to the modality. In this study, we show that the integrated stress response (ISR) is the most activated signaling pathway in radioresistant TNBC cells.

Postoperative Adjuvant Chemotherapy Improved the Prognosis in Locally Advanced Cervical Cancer Patients With Optimal Response to Neoadjuvant Chemotherapy.

Background: Few studies investigated the effectiveness of adjuvant chemotherapy (ACT) in patients with optimal response to neoadjuvant chemotherapy (NACT), and an optimal number of treatment cycles for these patients remains unknown.

Methods: A total of 261 Chinese patients with FIGO stage IB2-IIB cervical cancer who obtained an optimal response to NACT were included after radical surgery, and the disease-free survival (DFS) and overall survival (OS) of these patients treated with different cycles of postoperative ACT were compared using the Log-rank test and multivariate analysis.

Results: We found that the prognosis of optimal responders treated with postoperative ACT was significantly better than those without further adjuvant therapy.

Exosomes and breast cancer drug resistance.

Drug resistance is a daunting challenge in the treatment of breast cancer (BC). Exosomes, as intercellular communicative vectors in the tumor microenvironment, play an important role in BC progression. With the in-depth understanding of tumor heterogeneity, an emerging role of exosomes in drug resistance has attracted extensive attention.

Triple-negative breast cancer therapeutic resistance: Where is the Achilles' heel?

Triple-negative breast cancer (TNBC) shows a higher response rate to systemic therapy compared with other breast cancer subtypes. However, the tumor differentiation of TNBC is poorer, with an early tendency to metastasis and a higher recurrence rate. Relapsed and metastatic TNBCs usually progress more rapidly, showing strong resistance to chemotherapy and radiotherapy.

Cryptotanshinone strengthens the effect of gefitinib against non-small cell lung cancer through inhibiting transketolase.

Lung cancer is the leading cause of cancer-related mortality and causes more than a million deaths per year. Gefitinib is the first-line agent of advanced lung cancer, however, resistance to gefitinib becomes a major problem in clinical application. Transketolase (TKT) is a key enzyme functioning between the oxidative arm and the non-oxidative arm of the pentose phosphate pathway.

Sesamin Enhances Nrf2-Mediated Protective Defense against Oxidative Stress and Inflammation in Colitis via AKT and ERK Activation.

Ulcerative colitis (UC) is a major form of inflammatory bowel disease (IBD) with high incidence and prevalence in many countries. Patients with UC usually suffer from a lifetime of debilitating physical symptoms. Therefore, developing effective therapeutic strategy that can manage this disease better and improve patients' life quality is in urgent need.

Cancer stem cells in prostate cancer radioresistance.

Cancer stem cells (CSCs) in prostate cancer (CaP) are regarded as major contributors to radioresistance due to complex mechanisms including enhanced DNA repair, increased intracellular reactive oxygen species scavenging, activation of anti-apoptotic pathways, microenvironment hypoxia, epithelial-to-mesenchymal transition (EMT) and autophagy. They are also believed to cause tumour recurrence and metastasis due to their unique capability to survive and replicate the heterogeneity of the original tumour. Finding markers of prostate CSCs (PCSC) for identification, prognostication and targeting is key in enhancing therapeutic and clinical outcomes.

CHTOP in Chemoresistant Epithelial Ovarian Cancer: A Novel and Potential Therapeutic Target.

Chemoresistance is a major challenge in epithelial ovarian cancer (EOC) treatment. Chromatin target of protein arginine methyltransferase (CHTOP) was identified as a potential biomarker in chemoresistant EOC cell lines using label-free LC-MS/MS quantitative proteomics. Thus, the aim of this study is to investigate the role of CHTOP in chemoresistant EOC and the underlying mechanism.

Inhibition of PI3K/Akt/mTOR signaling pathway alleviates ovarian cancer chemoresistance through reversing epithelial-mesenchymal transition and decreasing cancer stem cell marker expression.

Background: Ovarian cancer is the most common malignant tumor of the female reproductive tract. Chemoresistance is a major challenge for current ovarian cancer therapy. However, the mechanism underlying epithelial ovarian cancer (EOC) chemoresistance is not completely uncovered.

Chromatin target of protein arginine methyltransferase regulates invasion, chemoresistance, and stemness in epithelial ovarian cancer.

Ovarian cancer is one of the most common gynecological cancers with a high mortality rate in females. Chromatin target of protein arginine methyltransferase (CHTOP) is an important intracellular protein that regulates the transcriptional activation of several oncogenic genes in glioblastomagenesis and controls mature mRNA export as a component of TRanscription-Export complex. However, the role of CHTOP in ovarian cancer is unclear.

Cancer stem cell in breast cancer therapeutic resistance.

Development of therapeutic resistance and metastasis is a major challenge with current breast cancer (BC) therapy. Mounting evidence suggests that a subpopulation of cancer stem cells (CSCs) contribute to the cancer therapeutic resistance and metastasis, leading to the recurrence and death in patients. Breast cancer stem cells (BCSCs) are not only a consequence of mutations that overactivate the self-renewal ability of normal stem cells or committed progenitors but also a result of the de-differentiation of cancer cells induced by somatic mutations or microenvironmental components under treatment.

Polymorphisms of peroxisome proliferator-activated receptor γ (PPARγ) and cluster of differentiation 36 (CD36) associated with valproate-induced obesity in epileptic patients.

Rationale: Valproate (VPA) is a choice for the treatment of primary generalized epilepsies and partial epilepsies. Unfortunately, weight gain or obesity is one of the most frequent adverse effects of VPA treatment. Genetic factors were shown to be involved in the effect.

Valproate induced hepatic steatosis by enhanced fatty acid uptake and triglyceride synthesis.

Steatosis is the characteristic type of VPA-induced hepatotoxicity and may result in life-threatening hepatic lesion. Approximately 61% of patients treated with VPA have been diagnosed with hepatic steatosis through ultrasound examination. However, the mechanisms underlying VPA-induced intracellular fat accumulation are not yet fully understood.

Emerging role of NRF2 in chemoresistance by regulating drug-metabolizing enzymes and efflux transporters.

Chemoresistance is a disturbing barrier in cancer therapy, which always results in limited therapeutic options and unfavorable prognosis. Nuclear factor E2-related factor 2 (NRF2) controls the expression of genes encoding cytoprotective enzymes and transporters that protect against oxidative stress and electrophilic injury to maintain intrinsic redox homeostasis. However, recent studies have demonstrated that aberrant activation of NRF2 due to genetic and/or epigenetic mutations in tumor contributes to the high expression of phase I and phase II drug-metabolizing enzymes, phase III transporters, and other cytoprotective proteins, which leads to the decreased therapeutic efficacy of anticancer drugs through biotransformation or extrusion during chemotherapy.

Cryptotanshinone Reverses Cisplatin Resistance of Human Lung Carcinoma A549 Cells through Down-Regulating Nrf2 Pathway.

Background/aims: To explore whether Nrf2 was associated with drug-resistance in cisplatin resistant A549 (A549/DDP) cells, and if cryptotanshinone (CTS), one of the bioactive compounds isolated from the roots of Salvia miltiorrhiza Bunge (Danshen), could enhance the sensitivity in A549/DDP cells towards cisplatin.

Methods: A549 and A549/DDP cells were subjected to various treatments, and then Sulforhodamine B (SRB) assay, flow cytometry analysis and western immunoblotting analysis were applied to determine IC50, apoptotic status and expressions of Nrf2 and its downstream genes.

Results: The endogenous expression levels of Nrf2 as well as its target genes including GCLC, GCLM, HO-1, NQO1 and MRP1 were much higher in A549/DDP cells than those of A549 cells and the susceptibility of A549/DDP cells to cisplatin was partially restored by silencing Nrf2.

3',4',5',5,7-pentamethoxyflavone sensitizes Cisplatin-resistant A549 cells to Cisplatin by inhibition of Nrf2 pathway.

Nuclear factor erythroid 2-related factor 2 (Nrf2) is an important redox-sensitive transcription factor that regulates the expression of several cytoprotective genes. More recently, genetic analyses of human tumors have indicated that Nrf2 may cause resistance to chemotherapy. In this study, we found that the expression levels of Nrf2 and its target genes GCLC, HO-1, NQO1 were significantly higher in cisplatin-resistant A549 (A549/CDDP) cells than those in A549 cells, and this resistance was partially reversed by Nrf2 siRNA.

Simultaneous determination of seven taxoids in rat plasma by UPLC-MS/MS and pharmacokinetic study after oral administration of Taxus yunnanensis extracts.

A rapid, sensitive and reliable method has been developed and validated for the simultaneous determination of seven taxoids including 10-deacetylbaccatin III (10-DAB III), baccatin III, 5-epi-canadensene, taxinine M, 10-deacetyltaxol (10-DAT), cephalomannine and paclitaxel in rat plasma using docetaxel as the internal standard (IS). The plasma samples were pretreated by liquid-liquid extraction with methyl tert-butyl ether. The chromatographic separation was achieved on a C18 column (50 mm × 2.