Tumor-associated macrophage subtypes on cancer immunity along with prognostic analysis and SPP1-mediated interactions between tumor cells and macrophages.

Tumor-associated macrophages (TAM) subtypes have been shown to impact cancer prognosis and resistance to immunotherapy. However, there is still a lack of systematic investigation into their molecular characteristics and clinical relevance in different cancer types. Single-cell RNA sequencing data from three different tumor types were used to cluster and type macrophages. Functional analysis and communication of TAM subpopulations were performed by Gene Ontology-Biological Process and CellChat respectively. Differential expression of characteristic genes in subpopulations was calculated using zscore as well as edgeR and Wilcoxon rank sum tests, and subsequently gene enrichment analysis of characteristic genes and anti-PD-1 resistance was performed by the REACTOME database. We revealed the heterogeneity of TAM, and identified eleven subtypes and their impact on prognosis. These subtypes expressed different molecular functions respectively, such as being involved in T cell activation, apoptosis and differentiation, or regulating viral bioprocesses or responses to viruses. The SPP1 pathway was identified as a critical mediator of communication between TAM subpopulations, as well as between TAM and epithelial cells. Macrophages with high expression of SPP1 resulted in poorer survival. By in vitro study, we showed SPP1 mediated the interactions between TAM clusters and between TAM and tumor cells. SPP1 promoted the tumor-promoting ability of TAM, and increased PDL1 expression and stemness of tumor cells. Inhibition of SPP1 attenuated N-cadherin and ß-catenin expression and the activation of AKT and STAT3 pathway in tumor cells. Additionally, we found that several subpopulations could decrease the sensitivity of anti-PD-1 therapy in melanoma. SPP1 signal was a critical pathway of communication between macrophage subtypes. Some specific macrophage subtypes were associated with immunotherapy resistance and prognosis in some cancer types.

The gut-liver axis perspective: Exploring the protective potential of polysaccharides from Cistanche deserticola against alcoholic liver disease.

The primary objective of this study is to investigate the potential mechanism behind the protective effect of Cistanche deserticola polysaccharides (CP) against alcoholic liver disease (ALD). Multiple chromography techniques were employed to characterize CP from polysaccharide, the molecular weight distribution of polysaccharides, monosaccharide composition, isomeric hydrogen and isomeric carbon, in order to clarify the material basis of CP. To create the ALD mouse model, we utilized the well-established Lieber-DeCarli alcoholic liquid feed method. Findings from the study revealed that CP administration resulted in significant improvements in intestinal permeability, upregulation of barrier proteins expression, and reduced levels of alanine aminotransferase (ALT) and aspartate aminotransferase (AST) in mouse liver and serum. Additionally, CP treatment reduced the presence of inflammatory cytokines both in serum and liver while enhancing the activity of antioxidant enzymes in the liver. Furthermore, CP effectively reduced alcohol-induced oxidative damage by downregulating Keap1 protein levels in the liver, leading to increased expression of Nrf2 protein. The 16S rDNA sequencing results revealed that CP significantly restored the intestinal microbiota composition in ALD mice. These findings establish a strong association between gut microbiota and liver injury indicators, highlighting the potential of CP in preventing and treating ALD by modulating the gut-liver axis.

Gold(III) derivatives as the noncovalent interaction donors: theoretical study of the π-hole regium bonds.

Except for the well-known σ-hole regium bonds formed by metal nanoparticles and M(I) (M = Cu, Ag, and Au) derivatives, the existence of π-hole regions located above and below the Au atom in gold(III) derivatives suggests that gold(III) also functions as an efficient electrophilic site. In this study, a comprehensive analysis was conducted on the electrophilicity of trichloro-(p-toluonitrilo-N)-gold(III) derivatives AuL3(NCC6H4X) (L = Cl, Br, CN; X = NH2, CH3, CF3, NC, and CN) and the nature of π-hole regium bonds in the AuL3(NCC6H4X)⋯LB (LB = NH3, N(NH3)3, CH2O, C2H2, C2H4, C6H6) and (AuCl3(NCC6H4Y))n (Y = Cl, CN, NC, NO2; n = 2, 3)) complexes. The characteristics of the π-hole regium bonds were studied with respect to the influence of ligands and substituents, the strength of intermolecular interactions between Au(III) derivatives and Lewis bases, and those in the polymers. In the case of the AuL3(NCC6H4X)⋯NH3 complexes, the strength of the regium bonds increases gradually in the order of L = Cl < Br < CN and X = NH2 < CH3 < CF3 ≈ NC < CN. The ligands (L) attached to the Au atom exert a significant effect on the strength of the π-hole regium bonds in comparison to the substituents (X) on the benzene ring. The regium bonds are primarily dominated by electrostatic interaction, accompanied by moderate contribution from polarization. Linear relationships were identified between the electrostatic energies and the local most positive potentials over the Au atom, as well as between the polarization energies and the amount of charge transfer. Most of the π-hole regium bonds in the AuL3(NCC6H4X)⋯LB complexes exhibit the characters of closed shell noncovalent interactions. In the polymers (AuCl3(NCC6H4Y))n, weak face-to-face π-π stacking interactions are also present, in addition to regium bonds. The trimers displayed a slightly negative cooperativity in comparison to the dimers.

Quantitative analysis and hepatoprotective mechanism of Cistanche deserticola Y. C. Ma against alcohol-induced liver injury in mice.

Cistanche deserticola Y. C. Ma (CD), known as "desert ginseng", has been found to have hepatoprotective effect. This research aimed to investigate the quality control and its alleviating effect on alcoholic liver injury in mice. In this study, for the first time, a sensitive and efficient ultra-high-performance liquid chromatography with quadrupole ion-trap mass spectrometry (UPLC-Q-TRAP/MS) method was developed to rapidly characterize nine representative phenylethanoid glycosides (PhGs) in the CD extract within 14 min, offering a reference for the quality control standard of this plant. In addition, we found that the CD extract significantly inhibited the weight loss, decreased the liver index, and attenuated excessive lipid deposition, inflammatory and oxidative stress in the mice liver. With the help of the high-throughput lipidomics technique, we discovered that CD markedly reversed 17 lipid metabolites and their involved linoleic acid, arachidonic acid and glycerophospholipid metabolic pathways. As these metabolites are mainly associated with lipid metabolism and liver damage, we further used molecular biological tests to found that CD could regulate the upstream genes and proteins of the lipid metabolism pathway, including adenosine 5'-monophosphate-activated protein kinase (AMPK), sterol regulatory element binding protein-1c (SREBP-1c), fatty acid synthase (FAS), and peroxidase proliferators activate receptors α (PPARα). In conclusion, this study elucidates the modulatory effects of CD on lipid metabolism disorders in alcoholic fatty liver from holistic system and provides a reference for further research and development of CD as a therapeutic agent.

Chronic stress in solid tumor development: from mechanisms to interventions.

Chronic stress results in disturbances of body hormones through the neuroendocrine system. Cancer patients often experience recurrent anxiety and restlessness during disease progression and treatment, which aggravates disease progression and hinders treatment effects. Recent studies have shown that chronic stress-regulated neuroendocrine systems secret hormones to activate many signaling pathways related to tumor development in tumor cells. The activated neuroendocrine system acts not only on tumor cells but also modulates the survival and metabolic changes of surrounding non-cancerous cells. Current clinical evidences also suggest that chronic stress affects the outcome of cancer treatment. However, in clinic, there is lack of effective treatment for chronic stress in cancer patients. In this review, we discuss the main mechanisms by which chronic stress regulates the tumor microenvironment, including functional regulation of tumor cells by stress hormones (stem cell-like properties, metastasis, angiogenesis, DNA damage accumulation, and apoptotic resistance), metabolic reprogramming and immune escape, and peritumor neuromodulation. Based on the current clinical treatment framework for cancer and chronic stress, we also summarize pharmacological and non-pharmacological therapeutic approaches to provide some directions for cancer therapy.

Targeting lipid metabolism for ferroptotic cancer therapy.

It has been 10 years since the concept of ferroptosis was put forward and research focusing on ferroptosis has been increasing continuously. Ferroptosis is driven by iron-dependent lipid peroxidation, which can be antagonized by glutathione peroxidase 4 (GPX4), ferroptosis inhibitory protein 1 (FSP1), dihydroorotate dehydrogenase (DHODH) and Fas-associated factor 1 (FAF1). Various cellular metabolic events, including lipid metabolism, can modulate ferroptosis sensitivity. It is worth noting that the reprogramming of lipid metabolism in cancer cells can promote the occurrence and development of tumors. The metabolic flexibility of cancer cells opens the possibility for the coordinated targeting of multiple lipid metabolic pathways to trigger cancer cells ferroptosis. In addition, cancer cells must obtain immortality, escape from programmed cell death including ferroptosis, to promote cancer progression, which provides new perspectives for improving cancer therapy. Targeting the vulnerability of ferroptosis has received attention as one of the significant possible strategies to treat cancer given its role in regulating tumor cell survival. We review the impact of iron and lipid metabolism on ferroptosis and the potential role of the crosstalk of lipid metabolism reprogramming and ferroptosis in antitumor immunity and sum up agents targeting lipid metabolism and ferroptosis for cancer therapy.

lncRNA and breast cancer: Progress from identifying mechanisms to challenges and opportunities of clinical treatment.

Breast cancer is a malignant tumor that has a high mortality rate and mostly occurs in women. Although significant progress has been made in the implementation of personalized treatment strategies for molecular subtypes in breast cancer, the therapeutic response is often not satisfactory. Studies have reported that long non-coding RNAs (lncRNAs) are abnormally expressed in breast cancer and closely related to the occurrence and development of breast cancer. In addition, the high tissue and cell-type specificity makes lncRNAs particularly attractive as diagnostic biomarkers, prognostic factors, and specific therapeutic targets. Therefore, an in-depth understanding of the regulatory mechanisms of lncRNAs in breast cancer is essential for developing new treatment strategies. In this review, we systematically elucidate the general characteristics, potential mechanisms, and targeted therapy of lncRNAs and discuss the emerging functions of lncRNAs in breast cancer. Additionally, we also highlight the advantages and challenges of using lncRNAs as biomarkers for diagnosis or therapeutic targets for drug resistance in breast cancer and present future perspectives in clinical practice.

[Effects of lipopolysaccharide and phytohaemagglutinin on the level of microRNAs in mouse peripheral blood mononuclear cells].

OBJECTIVE: To investigate the effects of lipopolysaccharide (LPS) and phytohaemagglutinin (PHA) on the level of microRNAs in mouse peripheral blood mononuclear cells (PBMCs). METHODS: The mouse PBMCs were cultured in vitro and stimulated with 100 ng/mL LPS for 1 hour or 2 hours and 2.5 µg/mL phytohaemagglutinin (PHA) for 2 hours or 4 hours, respectively. The levels of miR-9, miR-122-3p, miR-181d and miR-342-3p in both PBMCs and culture supernatants were determined by real-time quantitative PCR (qRT-PCR). RESULTS: The levels of miR-9, miR-122-3p, miR-181d and miR-342-3p in PBMCs and culture supernatants had no significant difference between blank control and LPS stimulation group, nor did between LPS stimulation 2 hours group and 1 hour group. The levels of miR-9, miR-122-3p and miR-342-3p in PBMCs and culture supernatant had no significant difference between blank control and PHA stimulation group, nor did between PHA stimulation 4 hours group and 2 hours group. However, compared with blank control, the expression of miR-181d significantly increased after PHA stimulation, while the time of stimulation did not affect the miR-181d level significantly. CONCLUSION: The stimulation of PHA could promote the expression and secretion of miR-181d in mouse PBMCs.