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Genome instability is a hallmark of cancer cells and can be accelerated by defects in cellular responses to DNA damage. This feature of malignant cells opens new avenues for tumor targeted therapy. MRE11-RAD50-NBS1 complex plays a crucial role in sensing and repair of DNA damage. Through interacting with other important players of DNA damage response, MRE11-RAD50-NBS1 complex is engaged in various DNA damage repair pathways. Mutations in any member of this complex may lead to hypersensitivity to genotoxic agents and predisposition to malignancy. It is assumed that the defects in the complex may contribute to tumorigenesis and that treatments targeting the defect may be beneficial to cancer patients. Here, we summarized the recent research findings of the role of MRE11-RAD50-NBS1 complex in tumorigenesis, cancer treatment and discussed the potential approaches of targeting this complex to treat cancer.

Immunotherapy with immune checkpoint inhibitor (ICI) drugs is gradually becoming a hot topic in cancer treatment. To comprehensively evaluate the safety and efficacy of ICI drugs, we employed the Bayesian model and conducted a network meta-analysis in terms of progression-free survival (PFS), overall survival (OS) and severe adverse events (AEs). Our study found that treatment with ipilimumab was significantly worse than standard therapies in terms of PFS, whereas treatment with cemiplimab significantly improved PFS. The results also indicated that cemiplimab was the best choice for PFS. Treatment with nivolumab, pembrolizumab and nivolumab plus ipilimumab significantly improved OS compared to standard therapies. In terms of OS, cemiplimab was found to be the best choice, whereas avelumab was the worst. In terms of severe AEs, atezolizumab, avelumab, durvalumab, nivolumab, and pembrolizumab all significantly reduced the risk of grade 3 or higher AEs compared to standard therapy. The least likely to be associated with severe AEs were as follows: cemiplimab, avelumab, nivolumab, atezolizumab, and camrelizumab, with nivolumab plus ipilimumab to be the worst. Therefore, different ICI drug therapies may pose different risks in terms of PFS, OS and severe AEs. Our study may provide new insights and strategies for the clinical practice of ICI drugs.

TIGAR is an important factor associated with tumor glucose metabolism, but its function and underlying mechanism in human lung cancer remains unclear. Here, we analyzed the expression changes, prognosis, genetic alteration, related gene networks and metabolic pathways of TIGAR in lung cancer. The findings revealed that TIAGR level was augmented in LUAD and LUSC in comparison to the normal lung tissue. In addition, high TIAGR level was related to poorer outcome of patients with LUAD. Different alterations in TIGAR gene at various sites were observed in both LUAD and LUSC. The GO/KEGG analyses indicated that TIGAR affects the occurrence and progress of lung cancer through multiple metabolic pathways. Further, we established lung cancer cell models with TIGAR knockdown or overexpression to explore its effects on glucose metabolism, apoptosis and chemosensitivity. Our results indicated that TIGAR markedly inhibited glucose metabolism, ROS production, and susceptibility of lung cancer cells to cisplatin. Together, TIGAR plays a cancer-promoting role in lung cancer, which becomes a promising prognostic and therapeutic biomarker.

The molecular programs that govern the directed differentiation of myeloid progenitor cells are still poorly defined. Using a previously established immortalized, phenotypically normal myeloid progenitor cell model mEB8-ER, we unveil a new mechanism mediated by STAT5 and STAT3 at a bifurcation point of myeloid progenitor cell-fate specification. We find that myeloid progenitor cells can spontaneously differentiate into neutrophils with a basal level of STAT3 phosphorylation, which is enhanced by G-CSF treatment or STAT3 over-expression, leading to elevated neutrophil differentiation. Reduced STAT3 phosphorylation caused by GM-CSF treatment, STAT3 specific inhibitor, or STAT3 depletion leads to attenuated myeloid differentiation into neutrophils, while elevating differentiation into monocytes/macrophages. In contrast, STAT5 appears to have an antagonistic function to STAT3. When activated by GM-CSF, STAT5 promotes myeloid differentiation into monocytes/macrophages but inhibits neutrophil differentiation. At the mechanistic level, GM-CSF activates STAT5 to up-regulate SOCS3, which attenuates STAT3 phosphorylation and consequently neutrophil differentiation, while enhancing monocyte/macrophage differentiation. Furthermore, inhibition of STAT5 and STAT3 in primary myeloid progenitors recapitulates the results from the mEB8-ER model. Together, our findings provide new mechanistic insights into myeloid differentiation and may prove useful for the diagnosis and treatment of diseases related to abnormal myeloid differentiation.

Chemoresistance is an obstacle of improving pancreatic cancer (PC) prognosis. However, the biological function of ISG15 in PC and whether it correlates with the resistance to chemotherapy are still unknown. Here, we aimed to reveal the clinical significance of ISG15 in PC and its regulatory mechanism in cancer progression and resistance to therapy. The level of ISG15, a protein involved in post-translational modifications, is elevated in PC tissues. Clinically, higher ISG15 expression correlates with higher PC grades, stronger resistance to treatment and poorer prognosis. Moreover, ISG15 promotes the proliferation, migration, invasion, colony formation of PC cells and resistance to Gemcitabine, a classic chemotherapeutics for PC, both and . ISG15 promotes progression and resistance to therapy in PC cells by binding to ATG7, reducing its degradation, and thereby leading to enhanced autophagy in PC cells. ISG15 may be used as both a potential diagnosis marker and sensitizer for chemotherapeutics such as Gemcitabine during PC intervention.

Repair of damaged DNA induced by radiation plays an important role in the development of radioresistance, which greatly restricts patients' benefit from radiotherapy. However, the relation between radioresistance development and DNA double-strand break repair pathways (mainly non-homologous end joining and homologous recombination) and how these pathways contribute to radioresistance are unclear. Here, we established a radioresistant breast cancer cell line by repeated ionizing radiation and studied the alteration in DNA repair capacity. Compared with parental sham-treated cells, radioresistant breast cancer cells present elevated radioresistance, enhanced malignancy, increased expression of Ataxia-telangiectasia mutated (ATM), and increased DNA damage repair efficiency, as reflected by accelerated γ-H2AX kinetic. These defects can be reversed by ATM inhibition or ATM knockdown, indicating a potential link between ATM, DNA repair pathway and radiosensitivity. We propose that cancer cells develop elevated radioresistance through enhanced DNA damage repair efficiency mediated by increased ATM expression. Our work might provide a new evidence supporting the potential of ATM as a potential target of cancer therapy.

Head and neck cancer (HNC) is the sixth leading cause of cancer death worldwide. Due to the low early diagnosis rate of HNC, local recurrence and high distant metastasis rate are the main reasons for treatment failure. Therefore, it is important to establish a method of diagnosis and monitoring, which is convenient, safe, reproducible, sensitive and specific. Compared with tissue biopsy, liquid biopsy is an emerging biopsy technique, which has the advantages of re-sampling, noninvasive and cost-effectiveness, and has shown good diagnostic and prognostic value in studies for various types of malignant solid tumors. This review introduces liquid biopsy, its research progress and prospects in HNC including early diagnosis, staging, grading, prognosis assessment and disease surveillance.

Purpose: Pt-based nanostructures are one of the promising nanomaterials for being used in catalysts, sensors, and therapeutics. However, their impacts on the health and biological systems are not adequately understood yet. Methods: In this work, nanorods composed of ultrasmall platinum (Pt) nanoparticles deposited on the surface and gold nanorod as the core (Au@Pt NRs) were synthesized, and the distribution and toxic effects of Au@Pt NRs were investigated in C57BL/6 mice with intravenous injection by using atomic absorption spectroscopy (AAS), transmission electron microscope (TEM), hematoxylin-eosin (HE) staining and blood cell analyzer. Results: At the time point of Day 1, Day 8 and Day 16 post injection of Au@Pt NRs (6 mg/kg of Pt atom), Au@Pt NRs were mainly accumulated in the liver and spleen. The energy dispersive spectrometer mapping images showed Au@Pt NRs experienced quick corrosion and Au released faster than Pt in the physiological environments. The catalase (CAT) activity in tissues increased slightly in the early stage of the Au@Pt NRs exposure and went down to the normal level. With HE staining, inflammatory cells infiltration could be seen in the tissues, while no significant influences were detected on the blood biochemistry and the function of liver and kidney. Conclusion: In conclusion, intravenously injected Au@Pt NRs mainly distributed in the liver and spleen with comparable levels, and did not exert any significant toxic effects on the organs' function within two weeks; meanwhile, Au@Pt NRs were able to degrade, which indicated acceptable safety to the mice and potentials of biomedical application. Keywords: noble metal nanoparticles, distribution, toxicity, oxidative stress, intravenous injection

Melatonin (MT) can protect plants against abiotic stress. In order to explore whether melatonin can improve photosynthetic function under NaCl stress, Solanum lycopersicum L. cv. Liaoyuanduoli were exposed to 150 mmol L −1 NaCl stress with or without pretreatment with 150 μmol L −1 melatonin. The results showed that NaCl stress can lead to reduced chlorophyll content, lower photosynthetic function, increased reaction oxygen species (ROS) levels, and decreased PSII activity. These changes were mainly due to the reduction in oxygen-evolving complex (OEC) activity on the donor side of PSII and the blockage of electron transfer from Q A to Q B on receptor side of PSII. The donor side of PSII was more sensitive to NaCl stress relative to the receptor side of PSII. Interestingly, application of MT enhanced tomato NaCl tolerance. MT reduced the production of ROS by balancing the distribution of photosynthetic electron flux, facilitated the repair of PSII by maintaining the abundance of Psb O and D1, and promoting the ability of the donor and acceptor sides of PSII to deliver electrons. MT also enhanced the scavenging ability of ROS by stimulating the activity of enzymes involved in the AsA-GSH cycle.

Abnormal glucose metabolism inevitably disrupts normal neuronal function, a phenomenon widely observed in Alzheimer’s disease (AD). Investigating the mechanisms of metabolic adaptation during disease progression has become a central focus of research. Considering that impaired glucose metabolism is closely related to decreased insulin signaling and insulin resistance, a new concept \"type 3 diabetes mellitus (T3DM)\" has been coined. T3DM specifically refers to the brain’s neurons becoming unresponsive to insulin, underscoring the strong link between diabetes and AD. Recent studies reveal that during brain insulin resistance, neurons exhibit mitochondrial dysfunction, reduced glucose metabolism, and elevated lactate levels. These findings suggest that impaired insulin signaling caused by T3DM may lead to a compensatory metabolic shift in neurons toward glycolysis. Consequently, this review aims to explore the underlying causes of T3DM and elucidate how insulin resistance drives metabolic reprogramming in neurons during AD progression. Additionally, it highlights therapeutic strategies targeting insulin sensitivity and mitochondrial function as promising avenues for the successful development of AD treatments.