Current Proteomics - Volume 21, Issue 1, 2024

Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck region known for its high metastatic and invasive potential. Chlorpromazine (CPZ) has been shown to inhibit the growth of oral cancer cells. However, the effects of CPZ on OSCC migration and its underlying molecular mechanisms remain unclear. Objectives: We aimed to identify global protein changes and potential core proteins involved in CPZ-mediated inhibition of migration in SCC-15 cells using proteomics. Methods: We assessed the effect of CPZ on SCC-15 using CCK-8 assays and wound healing experiments. Next, we performed LC-MS-based proteomic analysis to identify protein alterations in SCC-15 cells treated with CPZ at different times. Differential expression proteins (DEPs) were identified and subjected to bioinformatics analysis using GO, KEGG, and PPI tools. Key candidate proteins were selected and validated using the TCGA-HNSCC database and molecular docking. Results: It was found that 20μm of CPZ had no effect on cell proliferation, but inhibited cell migration. A total of 4748 proteins were identified by Proteomics, among which 56 DEPs were identified, including 34 upregulated proteins and 22 downregulated proteins. Three proteins (RPF2, ACTB, and TGFBI) were identified as key candidate proteins associated with cell adhesion and migration in oral cancer cells. Conclusion: CPZ may affect the expression of RPF2, ACTB, and TGFBI proteins and change the extracellular matrix and cell adhesion function, thus inhibiting the migration of SCC-15 cells. The results of this study provide a robust basis for further research on the molecular mechanism of CPZ to inhibit the migration of OSCC.

Background: Plasmodium falciparum (P. falciparum) heat shock proteins (PfHSP70s) are an important class of molecules critically involved in parasite survival during stress. Interaction between the cytosolic PfHSP70-1 and a crucial lipid modulator, Phosphatidylinositol 3 Phosphate (PI3P), stabilizes the parasite Digestive Vacuole (DV) to facilitate hemoglobin trafficking and breakdown, in turn impacting parasite survival. Methods: PI3P binding on PfHSP70-1 is facilitated by its C-terminal LID domain that controls substrate binding. PI3P and PfHSP70 homologs are amply expressed together in various subcellular compartments of the parasite, providing them with opportunities to interact and modulate biological processes. Results: Here, we have identified and analyzed the PI3P binding pockets of all four PfHSP70s by using structural bioinformatics tools to understand their interaction with this lipid. Our results show that differently localized PfHSP70 homologs bind PI3P with variable affinity. Conclusion: Analysis of these results has also helped to pinpoint specific residues on PfHSP70s that may be engaged in these interactions. The present study may, therefore, form the basis for designing interventions that hinder PfHSP70-PI3P interaction and influence parasite survival.

Background: Acinetobacter baumannii is an opportunistic pathogen that causes many infections, including nosocomial infections; this bacterium has a high mortality rate among other bacteria. A. baumannii has an elastic genome that changes rapidly when exposed to harsh environmental conditions, leading to widespread bacterial resistance to various disinfectants and antibiotics. The high ability of bacteria to bind to all surfaces and survive in different conditions has caused the spread of bacteria in various environments. Rapid detection is very important in preventing the spread and even treatment of the infection. Methods: Currently, the Polymerase Chain Reaction (PCR) method is the only effective method used for diagnosis, which has some pros and cons. Results and Conclusion: This study aimed to design a new recombinant multi-epitope protein from Acinetobacter baumannii that can be used in ELISA for rapid diagnosis. The unique feature of this study from others is the use of patient serum for antibody monitoring.

Background: Streptococcus equi ssp. zooepidemicus (SEZ) is one important pathogen. There are still sporadic outbreaks in China, northern United States and the Netherlands. Adenylosuccinate synthetase PurA, a newly discovered protein in prior research, requires further assessment of its protective effectiveness. Methods: In this study, we focused on the expression of recombinant PurA from SEZ ATCC 35246. We evaluated the immunoreactivity of this recombinant protein using convalescent minipig sera. Additionally, we conducted experiments in mice to assess its immunogenic properties. Results: Our findings revealed that the recombinant PurA triggered a substantial antibody response in mice, resulting in an 80% protection rate against SEZ infection. Notably, mice immunized with PurA exhibited significantly reduced bacterial colonization in all organs compared to the PBS control group. Furthermore, the levels of IL-6, IL-8, IL-1β, and TNF-α in mouse serum were significantly elevated in the PurA-immunized group compared to the control group. Hyperimmune sera targeting PurA effectively eliminated SEZ in bactericidal tests. Remarkably, antibodies against PurA demonstrated a significant inhibitory effect on developing SEZ biofilm. Conclusion: Immunization with PurA elicited robust humoral and cellular immune responses in mice. These promising results suggest the potential utility of PurA in developing SEZ vaccine immunogens, providing a valuable avenue for further research into SEZ infection prevention and control.