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.

Non-coding RNAs related to angiogenesis in gynecological cancer.

Gynecological cancer affects the female reproductive system, including ovarian, uterine, endometrial, cervical, vulvar, and vaginal tumors. Non-coding RNAs (ncRNAs), and in particular microRNAs, function as regulatory molecules, which can control gene expression in a post-transcriptional manner. Normal physiological processes like cellular proliferation, differentiation, and apoptosis, and pathological processes such as oncogenesis and metastasis are regulated by microRNAs. Numerous reports have shown a direct role of microRNAs in the modulation of angiogenesis in gynecological cancer, via targeting pro-angiogenic factors and signaling pathways. Understanding the molecular mechanism involved in the regulation of angiogenesis by microRNAs may lead to new treatment options. Recently the regulatory role of some long non-coding RNAs in gynecological cancer has also been explored, but the information on this function is more limited. The aim of this article is to explore the pathways responsible for angiogenesis, and to what extent ncRNAs may be employed as biomarkers or therapeutic targets in gynecological cancer.

Association between hypertension and clinical outcomes in COVID-19 patients: a case-controlled study.

The outbreak of coronavirus disease 2019 (COVID-19), which was originated from a severe acute respiratory syndrome-coronavirus-2 (SARS-COV-2) infection, has become an international public health emergency. The aim of this study was to assess the clinical symptoms and physical findings in both hypertensive and nonhypertensive patients infected with COVID-19. Methods: A retrospective observational case-control study with diagnosis of COVID-19 by laboratory-confirmed test was conducted on 280 consecutive unselected patients. This was a single-center study. The demographics, laboratory, and clinical findings data were extracted from the hospital registry database. Results: Of our 280 patients in the study, there were 149 men (53%) and 138 (50%) were older than 60 years (mean=67.75), and also 50 in-hospital deaths occurred (mortality rate, 17%). Total 19(6.9%) were taking opioid, and smoking. There were no significant differences in the rate of fever, cough, sputum production, gastrointestinal symptoms, myalgia, and headache in the both hypertensive and nonhypertensive groups. The prevalence of underlying diseases was significantly higher in older patients in comparison with younger ones (P=0<0.05), COVID-19 mortality was noticed to be higher among hypertensive patients as compared with nonhypertensive patients (P=0<0.05). Conclusion: Hypertension is associated with a poor prognosis and higher mortality among COVID-19 patients. Optimizing blood pressure is essential during the management of COVID-19. Our research implies the importance of early care and education of old patient with hypertension and other comorbidities.

Expression and Prognostic Significance of Stem Cell Marker CD133 in Survival Rate of Patients with Colon Cancer.

INTRODUCTION: Today, colon cancer is one of the most common types of gastrointestinal cancer worldwide. CD133 as a known cancer stem cell marker has been found effective in cell proliferation and differentiation in various cancers, including colon cancer. We aimed to investigate the relationship between CD133 expression in colon cancer with prognostic factors and survival rate of patients with colon cancer by immunohistochemistry. METHODS: Formalin-fixed paraffin-embedded (FFPE) tissue was taken from patients with colon cancer. Histopathology examination was done using hematoxylin and eosin staining. Immunohistochemistry was performed to determine CD133 expression. Association between CD133 expression and clinicopathological profile was then assessed. RESULTS: There was a statistically significant association between CD133 protein expression and sex , cancer stage, and lymphatic invasion (p = 0.044, p = 0.131, and p = 0.002, respectively). However, no significant correlation was identified between CD133 expression and other factors, including age of patients with colorectal cancer (CRC) (p = 0.267), tumor location (p = 0.494), tumor differentiation grade (p = 0.263), neural tissue invasion, and 5-year survival (p = 0.054). CONCLUSION: CD133 is a useful predictive or prognostic biomarker for CRC in clinical assessment and may serve as a potential therapeutic target for CRC.

Association of lower vitamin a levels in neonates and their mothers with increased risk of neonatal late-onset sepsis: A case-control study.

BACKGROUND: In developing countries, neonatal sepsis is one of the major causes of mortality and morbidity. Vitamin A deficiency also affects the immune system severely and is associated with various neonatal infections. We aimed to compare maternal and neonatal vitamin A levels among neonates with and without late-onset sepsis. MATERIAL AND METHODS: 40 eligible infants were entered into this case-control study according to inclusion criteria. The case group included 20 term or near-term infants who had late-onset neonatal sepsis from three to seven days of life. The control group consisted of 20 term or near-term infants who were icteric hospitalized neonates without sepsis. Demographic, clinical and paraclinical features, as well as neonatal and maternal vitamin A levels, were compared between the two groups. RESULTS: The average gestational age of the neonates was 37.1 ± 1.2, ranging from 35 to 39 days. There was a significant difference between the septic and non-septic groups in terms of white blood cell and neutrophil count, C-reactive protein, and neonatal and maternal vitamin A levels. A Spearman correlation analysis showed a significant direct correlation among maternal and neonatal vitamin A levels (correlation coefficient = 0.507; P-value = 0.001). Multivariate regression analysis showed that neonates' vitamin A level had a significant direct association with sepsis (OR: 0.541; P-value=0.017). CONCLUSION: Our findings demonstrated the association of lower vitamin A levels in neonates and their mothers with an increased risk of late-onset sepsis, which emphasizes the importance of the consideration of vitamin A level evaluation and its appropriate neonatal and maternal supplementation.

Potential of natural products in osteosarcoma treatment: Focus on molecular mechanisms.

Osteosarcoma is the most frequent type of bone cancer found in children and adolescents, and commonly arises in the metaphyseal region of tubular long bones. Standard therapeutic approaches, such as surgery, chemotherapy, and radiation therapy, are used in the management of osteosarcoma. In recent years, the mortality rate of osteosarcoma has decreased due to advances in treatment methods. Today, the scientific community is investigating the use of different naturally derived active principles against various types of cancer. Natural bioactive compounds can function against cancer cells in two ways. Firstly they can act as classical cytotoxic compounds by non-specifically affecting macromolecules, such as DNA, enzymes, and microtubules, which are also expressed in normal proliferating cells, but to a greater extent by cancer cells. Secondly, they can act against oncogenic signal transduction pathways, many of which are activated in cancer cells. Some bioactive plant-derived agents are gaining increasing attention because of their anti-cancer properties. Moreover, some naturally-derived compounds can significantly promote the effectiveness of standard chemotherapy drugs, and in certain cases are able to ameliorate drug-induced adverse effects caused by chemotherapy. In the present review we summarize the effects of various naturally-occurring bioactive compounds against osteosarcoma.

Cellulose-Based Nanofibril Composite Materials as a New Approach to Fight Bacterial Infections.

Antibiotic resistant microorganisms have become an enormous global challenge, and are predicted to cause hundreds of millions of deaths. Therefore, the search for novel/alternative antimicrobial agents is a grand global challenge. Cellulose is an abundant biopolymer with the advantages of low cost, biodegradability, and biocompatibility. With the recent growth of nanotechnology and nanomedicine, numerous researchers have investigated nanofibril cellulose to try to develop an anti-bacterial biomaterial. However, nanofibril cellulose has no inherent antibacterial activity, and therefore cannot be used on its own. To empower cellulose with anti-bacterial properties, new efficient nanomaterials have been designed based on cellulose-based nanofibrils as potential wound dressings, food packaging, and for other antibacterial applications. In this review we summarize reports concerning the therapeutic potential of cellulose-based nanofibrils against various bacterial infections.

Coumarins and Gastrointestinal Cancer: A New Therapeutic Option?

Cancers of the gastrointestinal (GI) tract are often life-threatening malignancies, which can be a severe burden to the health care system. Globally, the mortality rate from gastrointestinal tumors has been increasing due to the lack of adequate diagnostic, prognostic, and therapeutic measures to combat these tumors. Coumarin is a natural product with remarkable antitumor activity, and it is widely found in various natural plant sources. Researchers have explored coumarin and its related derivatives to investigate their antitumor activity, and the potential molecular mechanisms involved. These mechanisms include hormone antagonists, alkylating agents, inhibitors of angiogenesis, inhibitors of topoisomerase, inducers of apoptosis, agents with antimitotic activity, telomerase inhibitors, inhibitors of human carbonic anhydrase, as well as other potential mechanisms. Consequently, drug design and discovery scientists and medicinal chemists have collaborated to identify new coumarin-related agents in order to produce more effective antitumor drugs against GI cancers. Herein, we summarize the therapeutic effects of coumarin and its derivatives against GI cancer.