In silico design and immunoinformatics analysis of a chimeric vaccine construct based on Salmonella pathogenesis factors.

Currently, there are two vaccines based on killed and/or weakened Salmonella bacteria, but no recombinant vaccine is available for preventing or treating the disease. We used an in silico approach to design a multi-epitope vaccine against Salmonella using OmpA, OmpS, SopB, SseB, SthA and FilC antigens. We predicted helper T lymphocyte, cytotoxic T lymphocyte, and IFN-γ epitopes. The FilC sequence was used as a bovine TLR5 agonist, and the linkers KK, AAY, GPGPG and EAAAK were used to connect epitopes. The final sequence consisted of 747 amino acid residues, and the expressed soluble protein (∼79.6 kDa) was predicted to be both non-allergenic and antigenic. The tertiary structure of modeled protein was refined and validated, and the interactions of vaccine 3D structure were evaluated using molecular docking, and molecular dynamics simulation (RMSD, RMSF and Gyration). This structurally stable protein could interact with human TLR5. The C-ImmSim server predicted that this proposed vaccine likely induces an immune response by stimulating T and B cells, making it a potential candidate for further evaluation for the prevention and treatment of Salmonella infection.

Lipid management strategies for diabetic patients align with an evidence-based guideline.

BACKGROUND: Diabetes mellitus (DM) increases the risk of cardiovascular diseases (CVD) significantly. Statins are recommended for all diabetic patients aged ≥ 40 years to alleviate this risk. OBJECTIVES: This study aimed to determine the status of the implementation of the recommendations of lipid management strategies for diabetic patients. METHODS: In this cross-sectional study, 500 patients with DM, aged ≥ 40 referring to a public pharmacy with at least one diabetic medication in their prescription, were enrolled. Patients' demographics, lipid panel data, medications, personal and family history of atherosclerotic cardiovascular disease (ASCVD), and risk factors for ASCVD were documented. The appropriateness of stain dosing intensity was judged based on the American Diabetes Association (ADA) guideline. RESULTS: The mean ± SD of the age of patients was 61.39 ± 10.49 years. Among patients, 238 (47.6) were men. More than half of the patients were subject to receiving primary prevention (59.8%, n = 299). For 80.8% (n = 404) of patients, a statin, most frequently atorvastatin (61.8%), was prescribed. The appropriate statin dose based on the guideline for 470 patients (94%), was high-intensity statin. In 70.6% (n = 353) of patients, lipid management was not in accordance with the guideline. Patients with ASCVD were more likely to receive the statins and the appropriate doses compared to patients without ASCVD (p-value < 0.001). CONCLUSION: Despite a relatively high percentage of patients who received statins, the lipid management in most patients was not in accordance with the guideline. The profound problem was the suboptimal dosage of statins. Investigating the reasons and barriers of the appropriate management can be helpful. Additionally, since patients without ASCVD who should receive statins for primary prevention were significantly less likely to receive statins and evidence-based doses, more attention is needed for this population.

Exosomal long non-coding RNAs: novel molecules in gastrointestinal cancers' progression and diagnosis.

Gastrointestinal (GI) cancers arise in the GI tract and accessory organs, including the mouth, esophagus, stomach, liver, biliary tract, pancreas, small intestine, large intestine, and rectum. GI cancers are a major cause of cancer-related morbidity and mortality worldwide. Exosomes act as mediators of cell-to-cell communication, with pleiotropic activity in the regulation of homeostasis, and can be markers for diseases. Non-coding RNAs (ncRNAs), such as long non-coding RNAs (lncRNAs), can be transported by exosomes derived from tumor cells or non-tumor cells. They can be taken by recipient cells to alter their function or remodel the tumor microenvironment. Moreover, due to their uniquely low immunogenicity and excellent stability, exosomes can be used as natural carriers for therapeutic ncRNAs in vivo. Exosomal lncRNAs have a crucial role in regulating several cancer processes, including angiogenesis, proliferation, drug resistance, metastasis, and immunomodulation. Exosomal lncRNA levels frequently alter according to the onset and progression of cancer. Exosomal lncRNAs can therefore be employed as biomarkers for the diagnosis and prognosis of cancer. Exosomal lncRNAs can also monitor the patient's response to chemotherapy while also serving as potential targets for cancer treatment. Here, we discuss the role of exosomal lncRNAs in the biology and possible future treatment of GI cancer.

Antimetastatic Effects of Curcumin in Oral and Gastrointestinal Cancers.

Gastrointestinal (GI) cancers are known as frequently occurred solid malignant tumors that can cause the high rate mortality in the world. Metastasis is a significant destructive feature of tumoral cells, which directly correlates with decreased prognosis and survival. Curcumin, which is found in turmeric, has been identified as a potent therapeutic natural bioactive compound (Curcuma longa). It has been traditionally applied for centuries to treat different diseases, and it has shown efficacy for its anticancer properties. Numerous studies have revealed that curcumin inhibits migration and metastasis of GI cancer cells by modulating various genes and proteins, i.e., growth factors, inflammatory cytokines and their receptors, different types of enzymes, caspases, cell adhesion molecules, and cell cycle proteins. Herein, we summarized the antimetastatic effects of curcumin in GI cancers, including pancreatic cancer, gastric cancer, colorectal cancer, oral cancer, and esophageal cancer.