Navigating PRKCSH's impact on cancer: from N-linked glycosylation to death pathway and anti-tumor immunity.

PRKCSH, also known as Glucosidase II beta subunit (GluIIß), is a crucial component of the endoplasmic reticulum (ER) quality control system for N-linked glycosylation, essential for identifying and eliminating misfolded proteins. Glucosidase II consists of the catalytic alpha subunit (GluIIα) and the regulatory beta subunit (GluIIß), ensuring proper protein folding and release from the ER. The induction of PRKCSH in cancer and its interaction with various cellular components suggest broader roles beyond its previously known functions. Mutations in the PRKCSH gene are linked to autosomal dominant polycystic liver disease (ADPLD). Alternative splicing generates distinct PRKCSH isoforms, which can influence processes like epithelial-mesenchymal transition (EMT) and the proliferation of lung cancer cells. PRKCSH's involvement in cancer is multifaceted, impacting cell growth, metastasis, and response to growth factors. Additionally, PRKCSH orchestrates cell death programs, affecting both autophagy and apoptosis. Its role in facilitating N-linked glycoprotein release from the ER is hypothesized to assist cancer cells in managing increased demand and ER stress. Moreover, PRKCSH modulates anti-tumor immunity, with its suppression augmenting NK cell and T cell activity, promising enhanced cancer therapy. PRKCSH's diverse functions, including regulation of IGF1R and IRE1α, implicate it as a therapeutic target and biomarker in cancer immunotherapy. However, targeting its glucosidase II activity alone may not fully counteract its effects, suggesting broader mechanisms in cancer development. Further investigations are needed to elucidate PRKCSH's precise role and validate its therapeutic potential in cancer treatment.

Transcriptomic analysis of glucosidase II beta subunit (GluIIß) knockout A549 cells reveals its roles in regulation of cell adhesion molecules (CAMs) and anti-tumor immunity.

Glucosidase II beta subunit (GluIIß), encoded from PRKCSH, is a subunit of the glucosidase II enzyme responsible for quality control of N-linked glycoprotein folding and suppression of GluIIß led to inhibitory effect of the receptor tyrosine kinase (RTKs) activities known to be critical for survival and development of cancer. In this study, we investigated the effect of GluIIß knockout on the global gene expression of cancer cells and its impact on functions of immune cells. GluIIß knockout lung adenocarcinoma A549 cell line was generated using CRISPR/Cas9-based genome editing system and subjected to transcriptomic analysis. Among 23,502 expressed transcripts, 1068 genes were significantly up-regulated and 807 genes greatly down-regulated. The KEGG enrichment analysis showed significant down-regulation of genes related extracellular matrix (ECM), ECM-receptor interaction, cytokine-cytokine receptor interaction and cell adhesion molecules (CAMs) in GluIIß knockout cells. Of 9 CAMs encoded DEG identified by KEGG enrichment analysis, real time RT-PCR confirmed 8 genes to be significantly down-regulated in all 3 different GluIIß knockout clones, which includes cadherin 4 (CDH4), cadherin 2 (CDH2), versican (VCAN), integrin subunit alpha 4 (ITGA4), endothelial cell-selective adhesion molecule (ESAM), CD274 (program death ligand-1 (PD-L1)), Cell Adhesion Molecule 1 (CADM1), and Nectin Cell Adhesion Molecule 3 (NECTIN3). Whereas PTPRF (Protein Tyrosine Phosphatase Receptor Type F) was significantly decreased only in 1 out of 3 knockout clones. Microscopic analysis revealed distinctively different cell morphology of GluIIß knockout cells with lesser cytoplasmic and cell surface area compared to parental A549 cells and non-targeted transfected cells.Further investigations revealed that Jurkat E6.1 T cells or human peripheral blood mononuclear cells (PBMCs) co-cultured with GluIIß knockout A549 exhibited significantly increased viability and tumor cell killing activity compared to those co-cultured with non-target transfected cells. Analysis of cytokine released from Jurkat E6.1 T cells co-cultured with GluIIß knockout A549 cells showed significant increased level of angiogenin and significant decreased level of ENA-78. In conclusion, knockout of GluIIß from cancer cells induced altered gene expression profile that improved anti-tumor activities of co-cultured T lymphocytes and PBMCs thus suppression of GluIIß may represent a novel approach of boosting anti-tumor immunity.

Observation on therapeutic effects of Fuzheng Qingfei Decoction in treatment of 86 patients with AIDS complicating pulmonary infection / 重庆医学

Objective To observe the effects of Fuzheng Qingfei Decoction combined with Western medicine basic treatment in pulmonary infection of AIDS patients.Methods A total of 154 cases of AIDS pulmonary infection treated in the Affiliated Hospital of Southwest Medical University from November 2013 to December 2016 were selected.Among them,86 cases in the observation group adopted Fuzheng Qingfei Decoction combined with the Western medicine routine treatment;68 cases in the control group only adopted the Western medicine therapy.The levels of procalcitonin (PCT) and C-reactive protein (CRP),CD4+ T cells count and improvement situation of clinical symptoms in the two groups were observed before and after treatment.Results The CD4+ T cells count,levels of PCT and CRP before treatment had no statistical difference between the two groups (P＞0.05),the levels of PCT and CRP after 7 d treatment in the observation group were lower than those in the control group,the differences were statistically significant (P＜0.05),and the CD4+T cell count after 3-month treatment in the observation group was higher than that in the control group and the PCT and CRP levels were lower than those in the control group,the differences were statistically significant (P＜0.05);the total effective rate in the observation group was 87.21％,which was better than 76.74 ％ in the control group,the difference was statistically significant (P＜0.05).Conclusion Fuzheng Qingfei Decoction combined with routine Western medicine therapy for treating AIDS complicating pulmonary infection can increase the anti-infection effect,reduce the inflammatory response,enhance CD4+ T cells count,relieve the clinical symptoms and improve their living quality.

Evaluation of the relationship between HtrA and streptococcus mutans isolated from the children with different caries experience * / 重庆医学

Objective To evaluate the relationship between mRNA and protein expression of HtrA and Streptococcus mutans i-solated from the children with different caries experience and to provide the theoretical and experimental basis on prediction of dent-al caries in deciduous teeth .Methods The strains of Streptococcus mutans isolated from children with different carious experiences in the preliminary experiments were divided into three groups :high caries-susceptible group ,middle caries-susceptible group ,caries-free group .All strains were reanimated on the agar plate of MS ,and after smear pure culture examination ,typical bacteria were in-cubated in BHI ,then purified nucleic acid and extracted all the RNA of streptococcus mutans by reverse transcription PCR and de-tected it by agarose gel electrophoresis integrality .Synthetic cDNA and take further PCR amplification with cDNA products .Ob-serve records results by Gel imaging system .HtrA of target gene and electrophoresis image were gray scan by Gel quantitative soft-ware Gel-Pro analyzer 4 .0 was used to analyze relative expression value of gene .After purifying protein ,collected total protein of Streptococcus mutans strains by Western Blot method ,then tested the concentration of total protein sample .The results of Chemilu-minescence imaging were scanned into computer by Bio-Rad analyzing system ,calculated the gray value by software Quantity One 4 .4 .0 which showed the relative expression level of protein .Results There were significant differences in HtrA mRNA and protein expression of different Streptococcus mutans isolated from the children with different caries susceptibility .high caries-susceptible group> middle caries-susceptible group> caries-free group (P< 0 .05) .Conclusion There were significant differences in HtrA mRNA and protein expression of different Streptococcus mutans isolated from the children with different caries susceptibility .The higher caries susceptibility the group was ,the more HtrA mRNA and protein the strain express .