Long noncoding RNA DGCR5 suppresses gastric cancer progression by acting as a competing endogenous RNA of PTEN and BTG1.

Long noncoding RNA (lncRNA) DiGeorge syndrome critical region gene 5 (DGCR5) has been reported to correlate with a variety of cancers, with its expression pattern and potential mechanism not clarified in gastric cancer (GC). In this study, we demonstrated that DGCR5 was downregulated in cancerous tissues and plasma samples from patients with GC, and its downregulation was associated with advanced TNM stage and positive lymphatic metastasis. Plasma DGCR5 had an area under the receiver operating characteristic curve (AUC) of 0.722 for diagnosis of GC. Gain- and loss-of-function of DGCR5 revealed that DGCR5 functioned as a competing endogenous RNA for miR-23b to suppress GC cell proliferation, invasion and migration, and facilitate apoptosis by regulating PTEN and BTG1 in vitro. Furthermore, the overexpression of DGCR5 suppressed tumor growth, and inhibited the expression of miR-23b and proliferation antigen Ki-67, but increased the expression of PTEN and BTG1 in vivo. In conclusion, our results show that DGCR5 is a tumor-suppressive lncRNA that regulates PTEN and BTG1 expression through directly binding to miR-23b. This mechanism may contribute to a better understanding of GC pathogenesis and provide a potential therapeutic strategy for GC.

Emerging trends and hotspots in peptic ulcer from 2008 to 2023: A bibliometric analysis.

Peptic ulcer (PU) is a common digestive disorder in the gastroduodenal. Although bibliometrics has become very popular in the medical field, a bibliometric analysis of research related to PU has yet to be reported. Therefore, this research aims to analyze the trends and hotspots of PU in the last 15 years. Literature data related to PU retrieved from the Web of Science Core Collection database from 2008 to 2023 were visualized and analyzed using CiteSpace 6.1.6.msi, VOSviewer 1.6.19, and SCImago Graphica Beta 1.0.35. Six thousand four hundred ninety-one papers were collected based on inclusion and exclusion criteria. The country with the highest number of publications was China. The institution with the highest number of publications was Baylor College of Medicine. The most prolific author was Yamaoka Yoshio. Malfertheiner Peter had the highest number of citations. The journal with the most publications is World Journal of Gastroenterology. The most cited Journal is Gastroenterology. The most cited reference was published by Marshall B. J. et al in 1984. The article with the highest burst strength was published in 2012 by Malfertheiner Peter. The keyword with the highest burst strength was "oxidative stress." Our research provides a bibliometric analysis of PU research to reveal the trends and hotspots of PU for 2008 to 2023. Our findings will help researchers to quickly understand the current state of research and provide a reference for in-depth studies in this area to foster the development of PU research.

Feedback activation of EGFR/wild-type RAS signaling axis limits KRASG12D inhibitor efficacy in KRASG12D-mutated colorectal cancer.

Colorectal cancer (CRC), which shows a high degree of heterogeneity, is the third most deadly cancer worldwide. Mutational activation of KRASG12D occurs in approximately 10-12% of CRC cases, but the susceptibility of KRASG12D-mutated CRC to the recently discovered KRASG12D inhibitor MRTX1133 has not been fully defined. Here, we report that MRTX1133 treatment caused reversible growth arrest in KRASG12D-mutated CRC cells, accompanied by partial reactivation of RAS effector signaling. Through a drug-anchored synthetic lethality screen, we discovered that epidermal growth factor receptor (EGFR) inhibition was synthetic lethal with MRTX1133. Mechanistically, MRTX1133 treatment downregulated the expression of ERBB receptor feedback inhibitor 1 (ERRFI1), a crucial negative regulator of EGFR, thereby causing EGFR feedback activation. Notably, wild-type isoforms of RAS, including H-RAS and N-RAS, but not oncogenic K-RAS, mediated signaling downstream of activated EGFR, leading to RAS effector signaling rebound and reduced MRTX1133 efficacy. Blockade of activated EGFR with clinically used antibodies or kinase inhibitors suppressed the EGFR/wild-type RAS signaling axis, sensitized MRTX1133 monotherapy, and caused the regression of KRASG12D-mutant CRC organoids and cell line-derived xenografts. Overall, this study uncovers feedback activation of EGFR as a prominent molecular event that restricts KRASG12D inhibitor efficacy and establishes a potential combination therapy consisting of KRASG12D and EGFR inhibitors for patients with KRASG12D-mutated CRC.

Design, Synthesis, and Pharmacological Evaluation of Multisubstituted Pyrido[4,3-d]pyrimidine Analogues Bearing Deuterated Methylene Linkers as Potent KRASG12D Inhibitors.

The breakthrough in drug development of KRASG12C inhibitors provides inspiration for targeting alternative KRAS mutations, especially the most prevalent KRASG12D variant. Based on the structural analysis of MRTX1133 in complex with KRASG12D, a comprehensive structure-activity study was conducted, which led to the discovery of several compounds (22, 28, and 31) that showed higher potency in suppressing the clonogenic growth of KRASG12D-dependent cancer cells. These new compounds markedly and selectively inhibited the binding of RBD peptide to GTP-bound KRASG12D with IC50 values between 0.48 and 1.21 nM. These new inhibitors were found to have dose-dependent anti-tumor efficacy in the AsPC-1 xenograft mouse models with a tumor growth inhibition of approximately 70% at a dose of 20 mg/kg twice daily (i.p.). Despite the non-optimal pharmacokinetic properties similar to those of MRTX1133, the high in vitro and in vivo potency of these new inhibitors call for further profiling.

Analysis of the Effect of Sichs on Gastric Ulcer Rats Based on RNA Sequencing Technique.

Objective: To research the mechanism of action and transcriptomic characteristics for the intervention effect of self-made Chaihuang decoction (Sichs) on gastric ulcer (GU) rats with liver qi stagnation and spleen deficiency and to clarify the therapeutic pathway and effective target. Methods: Thirty SD rats were randomly divided into the control group, model group, and Sichs group (10 rats per group). The model of GU rats with liver qi stagnation and spleen deficiency was established through multifactor compound simulation of traditional Chinese medical (TCM) etiology and acetic acid method. Histopathological changes in the gastric antrum tissue were observed with H&E staining. RNA sequencing (RNA-seq) was utilized to check differentially expressed genes (DEGs) in the gastric antrum tissues of rats, and gene ontology (GO) and KEGG pathway enrichment analyses were performed. The key DEGs were validated using qRT-PCR. Results: Sichs could ameliorate gastric antrum tissue injury in GU rats with liver qi stagnation and spleen deficiency. After RNA-seq, it was found that Sichs could reverse 225 upregulated genes and 26 downregulated genes in the model group. And the DEGs between the Sichs group and the model group were related to cell division, complement activation, and phospholipase A2 (Pla2g2a) activity. According to KEGG pathway analysis, DEGs between the two groups were mainly enriched in signaling pathways such as cell cycle, p53 signaling pathway, and linolenic acid metabolism. The validation results of the four key DEGs were consistent with the analysis trend of sequencing results. Conclusion: Sichs can effectively improve GU with liver qi stagnation and spleen deficiency in rats through the signaling pathways related to cell cycle and lipid metabolism.

Hyperin Alleviates Triptolide-Induced Ovarian Granulosa Cell Injury by Regulating AKT/TSC1/mTORC1 Signaling.

Premature ovarian insufficiency (POI) is characterized by the loss of ovarian function before 40 years of age and affects approximately 1% of women worldwide. Caragana sinica is a traditional Miao (a Chinese ethnic minority) medicine that improves ovarian function and follicular development. In the present study, we aimed to investigate the effect of active ingredients of C. sinica on POI and determine underlying mechanisms. Herein, the chemical composition of the C. sinica compound was analyzed using ultra-high-performance liquid chromatography, which identified hyperin (HR) as one of the main ingredients in C. sinica. Then, interaction targets of HR and POI were predicted and analyzed using network pharmacology and bioinformatics. The effect of HR on triptolide (TP)-induced granulosa cell injury was evaluated, and the underlying mechanism was explored based on bioinformatic results. A total of 100 interaction targets for POI and HR were obtained. The protein-protein interaction network of identified interaction targets emphasized the topological importance of AKT1. Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis revealed that HR might regulate POI by modulating the mechanistic target of rapamycin (mTOR) signaling pathway. In addition, the KEGG graph of the mTOR signaling pathway revealed that AKT phosphorylation inhibits the TSC1/2, while TSC1/2 activation inhibits the expression of mTORC1. The fundamental experiment revealed that HR increased proliferation, progesterone receptor levels, and estradiol levels decreased by TP in KGN cells. Additionally, HR alleviated TP-induced apoptosis and G1/G1 phase arrest in KGN cells. Western blotting demonstrated that HR increased the phosphorylation of AKT and mTORC1 and decreased TSC1 expression in TP-induced KGN cells. Collectively, our findings revealed that HR alleviates TP-induced granulosa cell injury by regulating AKT/TSC1/mTORC1 signaling, providing insight into the treatment of POI.

[Study on illuminant spectrum qualifications for collecting tongue condition].

The traditional light sources in the diagnostic method of tongue collection such as daylight or even candles are easily affected by weather and environment. It isn't favorable for doctors to obtain the accurate information of the tongue condition. The authors' introduce the electric light sources to compensate or replace daylight to obtain stable and real tongue image and scientific results. Lighted by lamps with different radiation spectrum power distribution property, various color rendition and color temperature, the same object will indicate different colors. In this study, spectrum analysis is carried out on four fluorescent lamps and the research is based on iamge identification techniques of tongue color. Applying the methods of spectrum analysis, choose the best one in four illuminants with their specific spectrum by testing instruments and comparing with the results using several spectrum parameters and chromatic coordinates tolerance ellipses. Result showed PHILIPS YPZ220/18-3U. RR. D (with the correlative color temperature 6 500 K) lamp which has the most similar spectrum property with daylight can be used as standard lamp. The research provides the theoretic and experimental basis for choosing electric light sources to replace daylight.

[Evaluation of therapeutic effects of Chinese materia medica by tongue image analysis software 1.0 based on tongue colors].

OBJECTIVE: To evaluate the therapeutic effects of Chinese materia medica in treating patients with different syndromes by tongue image analysis software 1.0 based on tongue colors, and to discuss the feasibility of applying this computer science-based techniques into drug evaluation. METHODS: The tongue colors and the areas of tongue fur were examined and analyzed by the tongue image analysis software 1.0 in healthy persons and the patients with different syndromes before and after treatment. The parameters of tongue colors consisted of the followings: the hue (H), the lightness (L), the saturation (S), and the values of red (R), green (G) and blue (B). RESULTS: Obvious differences could be revealed in tongue color index between the healthy persons and the patients in five groups of different syndromes. There also existed some significant differences in those index between patients before and after treatment. CONCLUSION: The tongue image analysis software 1.0 based on tongue colors is helpful to evaluate the therapeutic effects of Chinese materia medica.

Tankyrase 2 (TNKS2) polymorphism associated with risk in developing non-small cell lung cancer in a Chinese population.

OBJECTIVES: We investigated the association between poly(ADP-ribose) polymerase Tankyrase 2 (TNKS2) single-nucleotide polymorphisms (SNPs) and the risk of developing non-small cell lung cancer (NSCLC) in a Han Chinese population. METHODS: Five-hundred NSCLC cases and 500 healthy controls were genotyped for four TNKS2 tagging SNPs (rs1538833, rs1538833, rs1340420, and rs1340420). The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) using multivariate unconditional logistic regression analyses. RESULTS: Individual alleles of the four TNKS2 SNPs were not associated with NSCLC risk in the studied Chinese population. However, patients carrying TNKS2 rs1340420 G/G and A/G genotypes were associated with a lower risk of developing NSCLC and adenocarcinoma (OR=0.14; 95% CI=0.02-1.15 and OR=0.11; 95% CI=0.03-0.91, respectively), whereas females patients homozygous for the TNKS2 rs1770474 T allele, a rare type, were associated with a higher risk of developing squamous-cell carcinoma (SCC) (OR=4.67; 95% CI=0.87-25.01). CONCLUSION: TNKS2 rs1340420 SNP was associated with lower NSCLC risk, whereas rs1770474 SNP was associated with higher SCC risk, suggesting that these two SNPs may be useful predictors of risk of developing NSCLC and SCC in this Chinese population.

Tankyrase 1 polymorphism associated with an increased risk in developing non-small cell lung cancer in a Chinese population: a proof-of-principle study.

OBJECTIVES: Tankyrase 1 (TNKS1), a poly (ADP-ribose) polymerase, regulates telomere length and apoptosis in cells, overexpression of which occurred in non-small cell lung cancer (NSCLC). This study investigated TNKS1 single-nucleotide polymorphisms (SNPs) for association with a risk in NSCLC development in a Chinese population. METHODS: NSCLC cases and healthy controls of 500 each were recruited for genotyping of 24 TNKS1 SNPs. The association between genotype and NSCLC risk was evaluated by computing the odds ratio (OR) and 95% confidence interval (CI) with multivariate unconditional logistic regression analyses. Haploview software was to analyze association between haplotypes and NSCLC risk. RESULTS: TNKS1 rs6601328 A allele was associated with a lower risk in developing NSCLC and adenocarcinoma (ADC) (OR=0.71; 95% CI, 0.51-0.99 and OR=0.70; 95% CI, 0.50-0.99), whereas TNKS1 rs11991621 C allele (OR=1.44; 95% CI, 1.03-2.03), rs11991621 C/C (OR=1.44, 95% CI, 1.03-2.35; P=0.03), and rs10503380 G/G (OR= 1.56, 95% CI, 1.09-2.50, P=0.02) were associated with a higher risk in developing NSCLC or ADC in females and rs6601328 A/A major allele (OR=1.39; 95% CI, 1.00-1.92; P=0.047) and rs7015700 G/G (OR= 1.51, 95% CI, 1.04-2.21) was associated with an increased NSCLC or ADC risk in males but a reduced NSCLC risk (OR=0.63; 95% CI, 0.42-0.96) and ADC risk (OR=0.64; 95% CI, 0.42-0.97) in females. Haploview showed that there were three Haplotype Blocks associated with NSCLC risk. However, TNKS1 rs12541709 C/C was associated with protective effect against ADC (OR=0.75; 95% CI, 0.56-0.99; P=0.04) in this Chinese population. CONCLUSION: TNKS1 SNPs (rs11991621 rs10503380, and rs7015700) were associated with NSCLC risk, whereas rs6601328 and rs12541709 inversely associated with NSCLC or ADC risk in this Chinese population.