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Hepatocellular carcinoma (HCC) remains an incurable malignancy despite the treatment methods being continually updated. Matrix metalloproteinases (MMPs) promote the progression of HCC; however, no consensus exists on which MMP plays the predominant role in HCCs. In the present study, we analyzed differentially expressed genes in HCCs, especially MMPs, compared with adjacent tissues using the Cancer Genome Atlas database. The KEGG enrichment pathway using differentially expressed genes included extracellular matrix–receptor interaction, which was correlated with MMPs. We found that among the MMP family, only MMP1, MMP3, MMP8, MMP9, MMP11, MMP12, MMP14, MMP15, MMP20, MMP21, and MMP24 significantly increased in HCCs compared with adjacent tissues. Crucially, survival and univariate analyses indicated that only MMPs 1, 9, 12, and 14 predict poor overall survival; however, multivariate Cox analysis and a nomogram demonstrated that only MMP1 is a poor prognostic biomarker for HCCs. In addition, we observed significant enrichment of uncharacterized cells but decreased macrophages in HCC tissues. Consistent with decreased macrophages in HCCs, MMP1 was negatively associated with macrophages but positively correlated with uncharacterized cells, indicating that the main producer of MMP1 is uncharacterized cells. Furthermore, MMP1 expression was negatively correlated with immune responses of HCCs. Taken together, our findings indicated that MMP1 is a poor and predominant prognostic biomarker for patients with HCC and that anti-MMP1 may be a novel therapy that is worth studying in depth. [ABSTRACT FROM AUTHOR]

To address the challenges of managing and mitigating the environmental impact posed by the large amount of underground residual soil generated during underground construction, a composite material known as recycled solidified soil (RSS) was developed using this underground construction residual soil. Through a series of laboratory tests, including mix design, slump spread, unconfined compressive strength, and X-ray diffraction, the basic properties and regenerative curing mechanism of RSS were investigated under various curing conditions, water-tosolid ratios (the total mass ratio of water to air-dried residual soil and cementitious material), cement mass fractions and mineral admixtures. The results show that the fluidity of the RSS can meet the requirements of general backfilling projects at a water-to-solid ratio of 0. 35. The unconfined compressive strength of the RSS increases with curing time, higher cement mass fractions and water-to-solid ratios under different curing conditions, with lower strength of underwater curing compared to indoor curing. The establishment of strength in the RSS is primarily attributed to the cementation between hydration products and soil particles. The findings of this study offer valuable insights into the treatment and resource utilization of engineering residues and serve as a reference for addressing these challenges. [ABSTRACT FROM AUTHOR]

Background and Aims: Patients with low HBV DNA levels (< 2000 IU/mL), HBV DNA negative, and HBsAg-negative hepatitis B virus(HBV)infection can still progress to decompensated cirrhosis; however, clinical research data in such patients, especially treatment-naïve patients, are currently insufficient. This study assessed the natural history of aforementioned patients.Methods: We retrospectively reviewed the data of 250 patients with HBV-associated decompensated cirrhosis(HBV DNA < 2000 IU/mL) who had not been treated with antiviral medication.Results: The mean age of the 250 patients was 53.90 ± 11.73 years and 183 patients (73.2%) were male. HBV DNA, HBsAg, and HBeAg positivity was detected in 77 (30.8%), 200 (80%), and 137 (54.8%) patients, respectively. HBsAg (odds ratio [OR], 3.303; 95% confidence interval [CI], 1.338-8.152; P = 0.010) and HBeAg (OR, 0.200; 95% CI, 0.107-0.376; P < 0.001) positivity were independent factors for low HBV DNA levels. The incidence of hepatocellular carcinoma (HCC) (P < 0.001) and portal vein thrombosis (P = 0.001) was higher in the low HBV DNA levels group. Multivariate analysis showed that HBV DNA positivity (OR, 3.548; 95% CI, 1.463-8.604; P = 0.005), HBeAg positivity (OR, 0.080; 95% CI, 0.022-0.289; P < 0.001), and glutamyltransferase (GGT) (OR, 1.003; 95% CI, 1.000-1.006; P = 0.040) were independent factors for HCC. Age was not related to the occurrence of cirrhosis complications.Conclusion: Patients with decompensated cirrhosis with HBV DNA < 2000 IU/mL still had severe liver damage and could develop severe cirrhosis complications. HCC risk was higher in low HBV DNA levels patients. HBsAg positivity and HBeAg negativity may be associated to the occurrence of low HBV DNA levels. [ABSTRACT FROM AUTHOR]

As a promising alternative platform for cellular immunotherapy, natural killer cells (NK) have recently gained attention as an important type of innate immune regulatory cell. NK cells can rapidly kill multiple adjacent cancer cells through non-MHC-restrictive effects. Although tumors may develop multiple resistance mechanisms to endogenous NK cell attack, in vitro activation, expansion, and genetic modification of NK cells can greatly enhance their anti-tumor activity and give them the ability to overcome drug resistance. Some of these approaches have been translated into clinical applications, and clinical trials of NK cell infusion in patients with hematological malignancies and solid tumors have thus far yielded many encouraging clinical results. CAR-T cells have exhibited great success in treating hematological malignancies, but their drawbacks include high manufacturing costs and potentially fatal toxicity, such as cytokine release syndrome. To overcome these issues, CAR-NK cells were generated through genetic engineering and demonstrated significant clinical responses and lower adverse effects compared with CAR-T cell therapy. In this review, we summarize recent advances in NK cell immunotherapy, focusing on NK cell biology and function, the types of NK cell therapy, and clinical trials and future perspectives on NK cell therapy. [ABSTRACT FROM AUTHOR]

Background: The phagocytosis checkpoints of CD47/SIRPα, PD1/PDL1, CD24/SIGLEC10, and MHC/LILRB1 have shown inhibited phagocytosis of macrophages in distinct tumors. However, phagocytosis checkpoints and their therapeutic significance remain largely unknown in intrahepatic cholangiocarcinoma (ICC) patients.Methods: We analyzed sequencing data from the Cancer Genome Atlas (TCGA) and identified differently expressed genes between tumors and para-tumors. Then, we investigated the expression of CD68, SIRPα, PD1, and SIGLEC10 by IHC in 81 ICC patients, and the clinical significance of these markers with different risk factors was also measured.Results: Tumor infiltration immune cells analysis from the TCGA data revealed that macrophages significantly increased. Further analysis showed that M0 macrophages were significantly higher and M2 macrophages were significantly lower in ICC compared with paracancerous tissues, while there was no significant difference in M1 macrophages. We then examined some of M1 and M2 markers, and we found that M1 markers (iNOS, TNF, IL12A, and B) increased, while M2 markers (ARG1 and CD206) decreased in ICCs compared with paracancerous tissues. Furthermore, the expression of CD68, SIRPα, PD1, and SIGLEC10 increased significantly, but LILRB1 expression did not. We also examined the expression of CD68, SIRPα, PD1, and SIGLEC10 in 81 ICC patients by IHC, which revealed a similar expression pattern to that which emerged from the TCGA data. Upon analyzing the correlation between these markers and the progression of ICC patients, we found that the high expression of CD68, SIRPα, and PD1 are correlated with poor progression among ICC patients, while SIGLEC10 shows no correlation. More SIRPα+ or PD1+ TAMs were observed in the tumor tissues of ICC patients with HBV infections compared to non-HBV-infected patients. Multivariate analysis indicated that SIRPα and PD1 expression are independent indicators of ICC patient prognosis.Conclusion: Hyperactivated CD47/SIRPα and PD1/PD-L1 signals in CD68+ TAMs in tumor tissues are negative prognostic markers for ICCs after resection. Furthermore, anti-CD47 in combination with anti-PD1 or CD47/PD1 bispecific antibody (BsAb) may represent promising treatments for ICC. Further studies are also required in the future to confirmed our findings. [ABSTRACT FROM AUTHOR]

Anemia is a significant complication of chronic inflammation and may be related to dysregulated activities among erythroblastic island (EBI) macrophages. GM-CSF was reported to be upregulated and attracted as a therapeutic target in many inflammatory diseases. Among EBIs, we found that the GM-CSF receptor is preferentially and highly expressed among EBI macrophages but not among erythroblasts. GM-CSF treatment significantly decreases human EBI formation in vitro by decreasing the adhesion molecule expression of CD163. RNA-sequence analysis suggests that GM-CSF treatment impairs the supporting function of human EBI macrophages during erythropoiesis. GM-CSF treatment also polarizes human EBI macrophages from M2-like type to M1-like type. In addition, GM-CSF decreases mouse bone marrow (BM) erythroblasts as well as EBI macrophages, leading to a reduction in EBI numbers. In defining the molecular mechanism at work, we found that GM-CSF treatment significantly decreases the adhesion molecule expression of CD163 and Vcam1 in vivo. Importantly, GM-CSF treatment also decreases the phagocytosis rate of EBI macrophages in mouse BM as well as decreases the expression of the engulfment-related molecules Mertk, Axl, and Timd4. In addition, GM-CSF treatment polarizes mouse BM EBI macrophages from M2-like type to M1-like type. Thus, we document that GM-CSF impairs EBI formation in mice and humans. Our findings support that targeting GM-CSF or reprogramming EBI macrophages might be a novel strategy to treat anemia resulting from inflammatory diseases. [ABSTRACT FROM AUTHOR]

Affiliation of Linping Xu and Meimei Yan was incorrect. Department of Research and Foreign Affairs, The Affiliated Cancer Hospital of Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450,008, China. [Extracted from the article]