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Background. To determine if the use of the Proton Pump Inhibitors (PPI) impacts the clinical efficacy of Immune Checkpoint Inhibitors (ICIs) in Non-Small Cell Lung Cancer (NSCLC), a meta-analysis was conducted. Method. Eleven studies from PubMed, EMBASE, Cochrane Library, Web of Science, and other databases up to May 2022, were selected. The pertinent clinical outcomes were assessed by applying the Progression-free survival (PFS), Overall Survival (OS), Hazard Ratio (HR), and 95% Confidence Interval (CI). Result. This study included eleven articles containing 7,893 NSCLC patients. The result indicated that PPI use was dramatically related to poor OS (HR: 1.30 [1.10–1.54]), and poor PFS (HR: 1.25 [1.09–1.42]) in case of patients treated with ICIs. With regard to the subgroup analysis, PPI use was dramatically associated with poor OS (Europe: HR = 1.48 [1.26, 1.74], Worldwide: HR = 1.54 [1.24, 1.91]), and poor PFS (Europe: HR = 1.36 [1.18, 1.57], Worldwide: HR = 1.34 [1.16, 1.55]) in patients from Europe and multi-center studies across the world, poor OS in patients with age less than or equal to 65 (HR = 1.56 [1.14, 2.15]), poor PFS in patients aged more than 65 (HR = 1.36 [1.18, 1.57]), poor OS for patients receiving with PD-1 (HR = 1.37 [1.04, 1.79]), poor PFS for patients receiving with PD-L1 (HR = 1.33 [1.19, 1.49]), and poor OS (−30: HR = 1.89 [1.29, 2.78], ±30: HR = 1.44 [1.27, 1.64]) and poor PFS (−30: HR = 1.51 [1.11, 2.05], ±30: HR = 1.32 [1.20, 1.45]) for patients who received PPI at 30 days before and/or after starting the ICIs treatment. Conclusion. Our meta-analysis indicated that PPI combined with ICIs in the treatment of NSCLC patients could result in poor OS and PFS. PPI use should be extremely cautious in clinical practices to avoid the impact on the efficacy of the ICIs.

DNA methylation has an important role in the development of carcinomas. As a metastasis suppressor gene, Raf kinase inhibitory protein (RKIP) suppresses tumor cell invasion and metastasis. In the present study, the associations between RKIP protein expression and promoter methylation with clinicopathological parameters, prognosis and survival rates in gastric adenocarcinoma were investigated. RKIP protein expression and promoter methylation were measured in 135 cases of surgically resected gastric adenocarcinoma specimens and corresponding normal tissues using immunohistochemistry and methylation-specific polymerase chain reaction, respectively. Kaplan-Meier analyses were performed to analyze the patient survival rate. Prognostic factors were determined using multivariate Cox analysis. RKIP promoter methylation was detected in 48.9% of gastric carcinoma tissues and 5.17% of adjacent tissues (P

Lung adenocarcinoma (AC) is one of the most deadly malignancies. The disease has a low five-year survival rate; therefore, the identification of novel therapeutic agents is required. This study aimed to investigate the effect of small interfering RNA (siRNA) targeting hypoxia‑inducible factor 1α (HIF‑1α) on the growth of AC A549 cells. A549 cells were transfected with various concentrations of HIF‑1α or control siRNA, and the effect on HIF‑1α expression was analyzed using quantitative polymerase chain reaction and western blot analysis. The effects of HIF-1α siRNA on growth inhibition and apoptosis were then assessed using standard methods. HIF‑1α siRNA treatment significantly reduced HIF‑1α mRNA and protein expression in A549 cells. Furthermore, the downregulation of HIF-1α expression inhibited the growth of A549 cells and induced apoptosis of A549 cells by upregulating caspase-3 expression. The present in vitro study demonstrates that the downregulation of HIF‑1α is capable of suppressing AC A549 cell growth, through the induction of apoptosis. This suggests that HIF‑1α inhibition may represent a promising strategy for the treatment of AC.

The effect of antigen specific immunotherapy (SIT) on asthma is supposed to be improved. Published data indicate that administration of probiotics alleviates allergic diseases. B cells play important roles in the pathogenesis of allergic diseases. This study aims to modulate antigen specific B cell property by the administration of Clostridium butyrate (CB) in combination with SIT. The results showed that after a 3-month treatment, the total asthma clinical score and serum specific IgE were improved in the patients treated with SIT, which was further improved in those treated with both SIT and CB, but not in those treated with CB alone. Treatment with SIT and CB increased p300 and STAT3 activation, up regulated the IL-10 gene transcription and increased the frequency of peripheral antigen specific B cells. In conclusion, administration with SIT in combination with CB converts Der p 1 specific B cells to regulatory B cells in asthma patients allergic to Der p 1. The data suggest a potential therapeutic remedy in the treatment of allergic diseases.

AIM: To determine the potential protective role of adiponectin in intestinal ischemia reperfusion (I/R) injury. METHODS: A rat model of intestinal I/R injury was established. The serum level of adiponectin in rats with intestinal I/R injury was determined by enzyme-linked immunosorbent assay (ELISA). The serum levels of interleukin (IL)-1β, IL-6, and tumor necrosis factor (TNF)-α were also measured by ELISA. Apoptosis of intestinal cells was detected using the terminal deoxynucleotidyl transferase dUTP nick end labeling assay. The production of malondialdehyde (MDA) and superoxide dismutase (SOD) and villous injury scores were also measured. RESULTS: Adiponectin was downregulated in the serum of rats with intestinal I/R injury compared with sham rats. No significant changes in the expression of adiponectin receptor 1 and adiponectin receptor 2 were found between sham and I/R rats. Pre-treatment with recombinant adiponectin attenuated intestinal I/R injury. The production of pro-inflammatory cytokines, including IL-6, IL-1β, and TNF-α, in rats with intestinal I/R injury was reduced by adiponectin pre-treatment. The production of MDA was inhibited, and the release of SOD was restored by adiponectin pre-treatment in rats with intestinal I/R injury. Adiponectin pre-treatment also inhibited cell apoptosis in these rats. Treatment with the AMP-activated protein kinase (AMPK) signaling pathway inhibitor, compound C, or the heme oxygenase 1 (HO-1) inhibitor, Snpp, attenuated the protective effects of adiponectin against intestinal I/R injury. CONCLUSION: Adiponectin exhibits protective effects against intestinal I/R injury, which may involve the AMPK/HO-1 pathway.

To investigate the cytotoxicity of normal CD8(+) T lymphocytes retrovirally transduced with WT1 peptide-specific T-cell receptor (TCR) genes against human lung cancer cells.HLA-A*2402-restricted and WT1 peptide-specific TCR-α/β genes were cloned from a cytotoxic T lymphocyte clone and inserted into a retroviral TCR expression vector. The cytotoxicity of normal peripheral CD8⁺ T cells transduced with the WT1-TCR genes against human lung cancer cells was evaluated using a standard ⁵¹Cr release assay.The WT1-TCR gene-modified T cells recognized the peptide-pulsed target cells but not the non-pulsed cells. TCR-redirected CD8⁺ T cells lysed WT1-overexpressing human lung cancer cells in an HLA-A*2402-restricted manner, but did not kill normal cells positively expressing HLA-A*2402.These data demonstrate the feasibility of adoptive immunotherapy with TCR-redirected T cell for the treatment of lung cancer.