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Lung cancer is one of the malignant tumors, and genetic background is a risk factor in lung cancer that cannot be neglected. In this study, we aimed to find out the effect of MRPS30-DT and NINJ2 variants on lung cancer risk. In this study, the seven selected single-nucleotide polymorphisms (SNPs) of MRPS30-DT and NINJ2 were genotyped in 509 lung cancer patients and 501 healthy controls based on the Agena MassARRAY platform. Odds ratios and 95% confidence intervals were calculated by logistic regression analysis to evaluate association between gene polymorphisms and lung cancer risk. False-positive report probability was also used to assess false-positive results. Furthermore, the interaction between SNPs was analyzed by multifactor dimensionality reduction to predict lung cancer risk. We identified the genotype TA of rs16901963 (T < A) in MRPS30-DT as a protective factor against lung cancer, while rs16901963-TT was significantly associated with an increased risk of lung cancer. We also revealed that the effect of MRPS30-DT and NINJ2 variants on the risk of lung cancer was dependent on age, gender, smoking, and drinking status. In conclusion, this study first proved that MRPS30-DT and NINJ2 variants played important roles in affecting the susceptibility to lung cancer.

Macrophages have been linked to tumor initiation, progression, metastasis, and treatment resistance. However, the transcriptional regulation of macrophages driving the protumor function remains elusive. Here, we demonstrate that the transcription factor c-Maf is a critical controller for immunosuppressive macrophage polarization and function in cancer. c-Maf controls many M2-related genes and has direct binding sites within a conserved noncoding sequence of the Csf-1r gene and promotes M2-like macrophage-mediated T cell suppression and tumor progression. c-Maf also serves as a metabolic checkpoint regulating the TCA cycle and UDP-GlcNAc biosynthesis, thus promoting M2-like macrophage polarization and activation. Additionally, c-Maf is highly expressed in tumor-associated macrophages (TAMs) and regulates TAM immunosuppressive function. Deletion of c-Maf specifically in myeloid cells results in reduced tumor burden with enhanced antitumor T cell immunity. Inhibition of c-Maf partly overcomes resistance to anti-PD-1 therapy in a subcutaneous LLC tumor model. Similarly, c-Maf is expressed in human M2 and tumor-infiltrating macrophages/monocytes as well as circulating monocytes of human non-small cell lung carcinoma (NSCLC) patients and critically regulates their immunosuppressive activity. The natural compound [beta]-glucan downregulates c-Maf expression on macrophages, leading to enhanced antitumor immunity in mice. These findings establish a paradigm for immunosuppressive macrophage polarization and transcriptional regulation by c-Maf and suggest that c-Maf is a potential target for effective tumor immunotherapy., Introduction Lung cancer remains the leading cause of cancer-related deaths worldwide, accounting for approximate 2.1 million new cases and 1.7 million deaths annually (1). Although cancer immunotherapy has been proclaimed [...]

The aim of this study was to evaluate the relationship between T helper type 17 (Th17) cells and Kawasaki disease (KD). Flow cytometry results showed that the number of Th17 cells in the peripheral blood mononuclear cells (PBMCs) of KD patients was significantly elevated. Enzyme-linked immunosorbent assay (ELISA) results showed that the serum concentrations of two Th17 cytokines, interleukin (IL)-17 and IL-6, were significantly increased in KD patients. In addition, real-time quantitative polymerase chain reaction (PCR) results showed that the messenger RNA (mRNA) expression of two molecules related to Th17 cell differentiation, retinoic acid–related orphan receptor C (RORC) and NR4A2, was upregulated in the CD4+ T cells of KD patients. Intravenous immunoglobulin (IVIG) infusion significantly reduced the proportion of Th17 cells, decreased serum concentrations of IL-7 and IL-6, and lowered the mRNA levels of RORC and NR4A2 in IVIG treatment–sensitive KD patients. Finally, the results of a Pearson's correlation analysis illustrated that IL-17 mRNA levels in CD4+ T cells of KD patients were positively correlated with NR4A2 but not RORC mRNA expression. Our results demonstrate that Th17 cells play an important role in KD development and IVIG treatment and that Th17 cells and IL-17 may be used as markers for the occurrence of KD or as treatment targets for KD therapies. In addition, our results suggest that the underlying mechanism of IL-17 production in KD is NR4A2 dependent. [ABSTRACT FROM AUTHOR]

Objective: The objective of this study is to investigate the diagnostic accuracy and prognostic value of amplitude-integrated electroencephalography (aEEG) in neonatal hypoxic ischemic encephalopathy (HIE)., Methods: Fifty-three neonates with HIE admitted to our hospital from February 2020 to September 2021 were included in the encephalopathy group, while 22 healthy neonates born in our hospital during the same period were included in the healthy group. The neonates were separated into three subgroups based on their aEEG results: normal, slightly abnormal, and severely abnormal. We investigated the correlation between aEEG monitoring and HIE clinical grading, as well as the rate of HIE abnormal prognosis, and we analyzed the prognostic value of aEEG in HIE., Results: The aEEGs of all neonates in the healthy group were normal. In the encephalopathy group, there were 24 neonates with normal aEEGs (including 20 with mild HIE and 4 with moderate HIE), 16 neonates with mildly abnormal aEEGs (including 4 with mild HIE, 10 with moderate HIE, and 2 with severe HIE), and 13 neonates with severely abnormal aEEGs (including 4 with moderate HIE and 9 with severe HIE). A very close correlation between aEEG monitoring results and HIE grading and prognosis was found (P < .05). The head circumference of neonates with severely abnormal aEEGs was smaller than that of the other two groups and was significantly smaller than that of the healthy group (P < .05). However, there was no significant difference in the body length and weight of neonates in the severely abnormal aEEG group when compared to other groups (P > .05)., Conclusion: The brain function of neonates with HIE can be accurately diagnosed with aEEG, and this diagnostic technique has a crucial application value in the early diagnosis and prognosis evaluation of neonatal HIE.

Objective: To investigate the expression of serum- and glucocorticoid-inducible kinase 1 (SGK1) in Kawasaki disease (KD) and explore the correlations between SGK1 and Th17 cell-related cytokines [retinoic-acid-related orphan nuclear receptor C (RORC), interleukin 17A (IL-17A), IL-6] in KD., Methods: Thirty patients with KD [(2.8 ± 1.4) years old], 30 healthy volunteers [(2.6 ± 1.6) years old] and 25 patients with infectious disease (ID) [(2.2 ± 1.5) years old] were recruited. The percentage of Th17 cells in CD4⁺ T cells was analyzed using flow cytometry. The mRNA levels of RORC and SGK1 in CD4⁺ T cells were detected using real-time quantitative PCR. The serum levels of IL-17A and IL-6 were analyzed by ELISA., Results: Compared with healthy volunteers and patients with ID, the percentage of Th17 cells in CD4⁺ T cells significantly increased in KD [(3.57 ± 0.62)% vs (0.51 ± 0.07)% or (1.72 ± 0.36)%]. The serum levels of IL-17A and IL-6 in KD were much higher than those in healthy volunteers and patients with ID. The mRNA levels of RORC and SGK1 in KD were remarkably elevated compared with healthy volunteers and patients with ID. The level of SGK1 in coronary artery lesion (CAL) group of KD was significantly higher than that in KD patients with normal coronary artery (CAN). SGK1 was reduced in KD after intravenous immunoglobulin (IVIG) treatment. What's more, the decrease of SGK1 was more obviously in the CAL group than in the CAN group. In addition, SGK1 expression in KD was positively correlated with RORC and IL-17A, but not with IL-6., Conclusion: SGK1 was up-regulated in CD4⁺ T cells and was positively correlated with RORC and IL-17A in the patients with KD.

Our previous studies identified UCA1 as a novel biomarker for bladder cancer and detected three variant transcripts of UCA1 in the human bladder TCC cell line BLZ-211 using northern blot analysis. One (1.4 kb) of the three transcripts has been shown to play a pivotal role in bladder cancer progression and embryonic development. In this study, we cloned a second transcript (2.2 kb), designated UCA1a, which was identical to previously reported cancer upregulated drug resistant gene (CUDR). Sequence comparison of UCA1 (1.4 kb transcript) and UCA1a(CUDR) cDNA revealed a 1,265 bp common region. Previous studies have demonstrated that CUDR is upregulated in various human tumors, including colon, cervical and lung cancer. However, the exact role of UCA1a(CUDR) in bladder cancer has not yet been reported. In this study, RT-PCR analysis indicated that UCA1a(CUDR) was also an embryonic development and bladder cancer-associated RNA. Overexpression of UCA1a(CUDR) significantly enhanced proliferation, migration and invasion of the bladder cancer cell line UM-UC-2. Moreover, microarray analysis demonstrated that overexpression of UCA1a(CUDR) was associated with signaling pathways regulating cell apoptosis and tumorigenesis. Furthermore, overexpression of UCA1a(CUDR) could antagonize cell apoptosis induced by cisplatin and promote the tumorigenicity of UM-UC-2 cells in vivo. Taken together, our data strongly suggest that similar to the 1.4 kb transcript of UCA1, UCA1a(CUDR) may also play an important role in the growth and tumorigenesis of human bladder cancer, and their common region may be critical for biological activity, thereby indicating that their common region may serve as a new therapeutic target for bladder cancer.