The distribution and abundance of immune cells, particularly T‐cell subsets, play pivotal roles in cancer immunology and therapy. T cells have many subsets with specific function and current methods ...are limited in estimating them, thus, a method for predicting comprehensive T‐cell subsets is urgently needed in cancer immunology research. Here, Immune Cell Abundance Identifier (ImmuCellAI), a gene set signature‐based method, is introduced for precisely estimating the abundance of 24 immune cell types including 18 T‐cell subsets, from gene expression data. Performance evaluation on both the sequencing data with flow cytometry results and public expression data indicate that ImmuCellAI can estimate the abundance of immune cells with superior accuracy to other methods especially on many T‐cell subsets. Application of ImmuCellAI to immunotherapy datasets reveals that the abundance of dendritic cells, cytotoxic T, and gamma delta T cells is significantly higher both in comparisons of on‐treatment versus pre‐treatment and responders versus non‐responders. Meanwhile, an ImmuCellAI result‐based model is built for predicting the immunotherapy response with high accuracy (area under curve 0.80–0.91). These results demonstrate the powerful and unique function of ImmuCellAI in tumor immune infiltration estimation and immunotherapy response prediction.
Immune Cell Abundance Identifier (ImmuCellAI) is a gene set signature‐based method for precisely estimating the abundance of 24 immune cell types including 18 T‐cell subsets. Application of ImmuCellAI to immunotherapy datasets reveals the dynamic change of immune cell abundance. An ImmuCellAI result‐based model for predicting the immunotherapy response achieves high accuracy with area under curve 0.80–0.91.
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FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
The clearance of activated hepatic stellate cells (HSCs) by apoptosis is critical for the reversibility of hepatic fibrosis. Mitochondrial homeostasis is regulated by mitophagy, which is an efficient ...way of clearing injured mitochondria that plays an important role in apoptosis. However, the role of mitophagy in apoptosis in HSCs and hepatic fibrosis is still unclear. Here, we show that mitophagy is enhanced in parallel with increased apoptosis in hepatic stellate cells during the reversal of hepatic fibrosis. The inhibition of mitophagy suppressed apoptosis in HSCs and aggravated hepatic fibrosis in mice. In contrast, the activation of mitophagy induced apoptosis in HSCs. Furthermore, we confirmed that BCL-B, which is a member of the BCL-2 family, is a regulator mediating mitophagy-related apoptosis. The knockdown of BCL-B resulted in increased apoptosis and mitophagy in HSCs, while the overexpression of BCL-B caused the opposite effects. BCL-B inhibited the phosphorylation of Parkin (a key regulator of mitophagy) and directly bound phospho-Parkin. Altogether, enhanced mitophagy promotes apoptosis in HSCs during the reversal of hepatic fibrosis. BCL-B suppresses mitophagy in HSCs by binding and suppressing phospho-Parkin, thereby inhibiting apoptosis. BCL-B-dependent mitophagy is a new pathway for the regulation of apoptosis in HSCs during the regression of hepatic fibrosis.
Background and Objectives
This study aimed to compare outcomes between neoadjuvant imatinib and upfront surgery in patients with localized rectal gastrointestinal stromal tumors (GIST) patients.
...Methods
Eighty‐five patients with localized rectal GIST were divided into two groups: upfront surgery ± adjuvant imatinib (Group A, n = 33) and the neoadjuvant imatinib + surgery + adjuvant imatinib (Group B, n = 52). Baseline characteristics between groups were controlled for with inverse probability of treatment weighting (IPTW) adjusted analysis.
Results
The response rate to neoadjuvant imatinib was 65.9%. After the IPTW‐adjusted analysis, patients who underwent neoadjuvant therapy had better distant recurrence‐free survival (DRFS) and disease‐specific survival (DSS) compared with those who underwent upfront surgery (5‐year DRFS 97.8 vs. 71.9%, hazard ratio HR, 0.15; 95% CI, 0.03–0.87; p = 0.03; 5‐year DSS 100 vs. 77.1%; HR, 0.11; 95% CI, 0.01–0.92; p = 0.04). While no significant association was found between overall survival (OS) and treatment groups (p = 0.07), 5‐year OS was higher for the neoadjuvant group than upfront surgery group (97.8% vs. 71.9%; HR, 0.2; 95% CI, 0.03–1.15).
Conclusions
In patients with localized rectal GIST, neoadjuvant imatinib not only shrunk the tumor size but also decreased the risk of metastasis and tumor‐related deaths when compared to upfront surgery and adjuvant imatinib alone.
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BFBNIB, FZAB, GIS, IJS, KILJ, NLZOH, NUK, OILJ, SBCE, SBMB, UL, UM, UPUK
Breast cancer is a significant threat to life and health, which needs more safe and effective drugs to be explored. Teadenol B is a characteristic chemical component of microbial fermented tea. This ...study discovered that teadenol B could exhibit obvious inhibitory effects on all four different clinical subtype characteristics of breast cancer cells. Proteomic studies show that deoxycytidine triphosphate deaminase (DCTD), which could block DNA synthesis and repair DNA damage, had the most significant and consistent reduction in all four types of breast cancer cells with the treatment of teadenol B. Considering MDA-MB-231 cells exhibit poor clinical prognosis and displayed substantial statistical differences in KEGG pathway enrichment analysis results, we investigated its impact on the size and growth of MDA-MB-231 triple-negative breast tumors transplanted into nude mice and demonstrated that teadenol B significantly suppressed tumor growth without affecting body weight significantly. Finally, we found that the conversion of LC3-I to LC3-II in MDA-MB-231 increased significantly with teadenol B treatment. This proved that teadenol B could be a strong autophagy promotor, which explained the down-regulation of DCTD to some extent and may be the potential mechanism underlying teadenol B's anti-breast cancer effects. This finding provides new evidence for drinking fermented tea to prevent breast cancer and highlights the potential of teadenol B as a novel therapeutic option for breast cancer prevention and treatment, necessitating further investigations to clarify its exact target and the details involved.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Mitophagy affects the activation of hepatic stellate cells (HSCs). Mitochondria-targeted ubiquinone (MitoQ) is a mitochondria-targeted antioxidant that reduces the production of intracellular ...reactive oxygen species (ROS). However, its relationship with mitophagy remains unclear. This study evaluated mitophagy during HSC activation and the effects of MitoQ on mitophagy in cell culture and in an animal model of the activation of HSCs. We found that MitoQ reduced the activation of HSCs and alleviated hepatic fibrosis. PINK1 (PTEN-induced putative kinase 1) is a putative serine/threonine kinase located in the mitochondria’s outer membrane. While the activation of primary HSCs or LX-2 cells was associated with reduced PINK1/parkin-mediated mitophagy, MitoQ reduced intracellular ROS levels, enhanced PINK1/parkin-mediated mitophagy, and inhibited the activation of HSCs. After knocking down the key mitophagy-related protein, PINK1, in LX-2 cells to block mitophagy, MitoQ intervention failed to inhibit HSC activation. Our results showed that MitoQ inhibited the activation of HSCs and alleviated hepatic fibrosis by enhancing PINK1/parkin-mediated mitophagy.
The inoculation response of single arbuscular mycorrhiza fungi (AMF) or rhizobia (Rh) in relation to nitrogen (N) acquisition of plants is well established, while the combined effect of both AMF and ...Rh is poorly known with regard to N assimilation for changes in amino acids of white clover (
Trifolium repens
). A pot study was carried out to evaluate the effect of single versus dual inoculation of AMF (
Rhizophagus intraradices
) and rhizobium (
Rhizobium trifolii
) on plant growth, leaf and root N contents, root amino acid contents, and root N-related enzyme activities in white clover. One hundred days after inoculations, Rh inoculation significantly stimulated the root colonization by
R
.
intraradices
. A single inoculation of AMF or Rh improved the plant growth (biomass production, root projected area, and root volume), root N acquisition, and dual inoculation of AMF and Rh further expanded some of these positive effects on root projected area and root N contents than single inoculation. All the inoculations notably increased activities of root asparagines synthase, nitrate reductase, and glutamate synthase, whilst dual inoculation displayed a much stronger effect in asparagine synthase activity than single inoculation. Single Rh treatment increased root glutamate and proline content, single AMF inoculation induced an increase in glutamate, aspartate, arginine, and ornithine content, while dual inoculation stimulated the accumulation of aspartate and proline. These results suggested the cooperation between the AMF and Rh inoculations, which magnified the positive effect on partly N metabolites and N-assimilation relevant enzymes of white clover.
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EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Autoimmune diseases are often treated by glucocorticoids and immunosuppressive drugs that could increase the risk for infection, which in turn deteriorate disease and cause mortality. Low-dose IL-2 ...(Ld-IL2) therapy emerges as a new treatment for a wide range of autoimmune diseases. To examine its influence on infection, we retrospectively studied 665 patients with systemic lupus erythematosus (SLE) including about one third receiving Ld-IL2 therapy, where Ld-IL2 therapy was found beneficial in reducing the incidence of infections. In line with this clinical observation, IL-2 treatment accelerated viral clearance in mice infected with influenza A virus or lymphocytic choriomeningitis virus (LCMV). Noticeably, despite enhancing anti-viral immunity in LCMV infection, IL-2 treatment exacerbated CD8
+
T cell-mediated immunopathology. In summary, Ld-IL2 therapy reduced the risk of infections in SLE patients and enhanced the control of viral infection, but caution should be taken to avoid potential CD8
+
T cell-mediated immunopathology.
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DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Although fish are widely confirmed to be susceptible to heavy metals (HMs) contamination in sediments, this bioconversion haven’t been detailed. This is especially the case in karst areas, where HMs ...are less stably retained in the sediments and are more bioavailable. Therefore, we surveyed representative karst rivers in Liuzhou, China, in order to study the relationship between the speciations of seven HMs in the sediments with their bioaccumulation in wild fish. The results showed that the HMs in sediments are all below their permissible exposure limit (PEL), but Cd and Zn are significantly higher than soil basline. Most HMs are in residual fraction, while their exchangeable fractions are present in extremely low proportions. The concentration of Zn, Cr and Cd in some fish are above their maximum recommended limit (MRL). The concentrations of most of the HMs in the fish are significantly correlated with the levels in the sediments and given the higher correlation coefficients for their carbonate-bound phase, this phase can be seen to play a critical role in HMs bioconversion. However, the presence of this phase in low proportions enables other phases, especially oxidizable form, to play a greater role in HMs bioaccumulation. Apart from Do, HMs in the fish samples are significantly correlated with multiple environmental factors, demonstrating environmental fluctuations can manipulate HMs bioconversion from sediments; however, their significance depend heavily on the proportion of particular species. HMs in reducible and oxidizable fraction are more important in regulating, rather than promoting, their bioconversion during environmental fluctuations. Fluctuations in EC, TDS and pH can increase the impacts of HMs in carbonate-bound fraction on their bioconversion. Given the higher background values of EC and TDS and lower pH values during the monsoon period, careful attention should be paid to the increased bioconversion of HMs in karst rivers during this season.
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•Linkage of heavy metals speciation in sediments with their bioaccumualtion in fish in a karst river.•Heavy metals in the carbonate-bound phase are very important for their bioconversion.•Environmental fluctuations can significant impact heavy metals bioconversion from sediments.•Heavy metals in reducible and oxidizable forms can affect their bioaccumulation.•pH, EC and TDS fluctuations may increase the impacts of carbonate-bound fraction of HMs in bioconversion.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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