Chitosan-LeoA-DNA Nanoparticles Promoted the Efficacy of Novel LeoA-DNA Vaccination on Mice Against Helicobacter pylori.

More than half of the world's population is infected with Helicobacter pylori (H. pylori), which may lead to chronic gastritis, peptic ulcers, and stomach cancer. LeoA, a conserved antigen of H. pylori, aids in preventing this infection by triggering specific CD3+ T-cell responses. In this study, recombinant plasmids containing the LeoA gene of H. pylori are created and conjugated with chitosan nanoparticle (CSNP) to immunize BALB/c mice against the H. pylori infection. We used the online Vaxign tool to analyze the genomes of five distinct strains of H. pylori, and we chose the outer membrane as a prospective vaccine candidate. Afterward, the proteins' immunogenicity was evaluated. The DNA vaccine was constructed and then encapsulated in CSNPs. The effectiveness of the vaccine's immunoprotective effects was evaluated in BALB/c mice. Purified activated splenic CD3+ T cells are used to test the anticancer effects in vitro. Nanovaccines had apparent spherical forms, were small (mean size, 150-250 nm), and positively charged (41.3 ± 3.11 mV). A consistently delayed release pattern and an entrapment efficiency (73.35 ± 3.48%) could be established. Compared to the non-encapsulated DNA vaccine, vaccinated BALB/c mice produced higher amounts of LeoA-specific IgG in plasma and TNF-α in splenocyte lysate. Moreover, BALB/c mice inoculated with nanovaccine demonstrated considerable immunity (87.5%) against the H. pylori challenge and reduced stomach injury and bacterial burdens in the stomach. The immunological state in individuals with GC with chronic infection with H. pylori is mimicked by the H. pylori DNA nanovaccines by inducing a shift from Th1 to Th2 in the response. In vitro human GC cell development is inhibited by activated CD3+ T lymphocytes. According to our findings, the H. pylori vaccine-activated CD3+ has potential immunotherapeutic benefits.

Use of immunoinformatics and the simulation approach to identify Helicobacter pylori epitopes to design a multi-epitope subunit vaccine for B- and T-cells.

BACKGROUND: Helicobacter pylori cause a variety of gastric malignancies, gastric ulcers, and cause erosive diseases. The extreme nature of the bacterium and the implantation of this bacterium protects it against designing a potent drug against it. Therefore, employing a precise and effective design for a more safe and stable antigenic vaccine against this pathogen can effectively control its associated infections. This study, aimed at improving the design of multiple subunit vaccines against H. pylori, adopts multiple immunoinformatics approaches in combination with other computational approaches. RESULTS: In this regard, 10 HTL, and 11 CTL epitopes were employed based on appropriate adopted MHC binding scores and c-terminal cut-off scores of 4 main selected proteins (APO, LeoA, IceA1, and IceA2). An adjuvant was added to the N end of the vaccine to achieve higher stability. For validation, immunogenicity and sensitization of physicochemical analyses were performed. The vaccine could be antigenic with significantly strong interactions with TOLK-2, 4, 5, and 9 receptors. The designed vaccine was subjected to Gromacs simulation and immune response prediction modelling that confirmed expression and immune-stimulating response efficiency. Besides, the designed vaccine showed better interactions with TLK-9. CONCLUSIONS: Based on our analyses, although the suggested vaccine could induce a clear response against H. pylori, precise laboratory validation is required to confirm its immunogenicity and safety status.

Effect of Metformin Treatment on Insulin Resistance Markers, and Circulating Irisin in Women with Polycystic Ovarian Syndrome (PCOS).

Polycystic ovarian syndrome (PCOS) is considered as a common endocrinal dysfunction among adult women characterized by polycystic ovaries, anovulation, and hyperandrogenism. Irisin is associated with metabolic parameters and insulin resistance. However, the association of irisin with PCOS remains poorly delineated. This study was aimed to examine circulating irisin levels and effects of metformin on this parameter in women with PCOS. Moreover, the association of irisin with insulin resistance markers was determined. Thirty-nine females with PCOS, aged 20-40 years, participated in this study and received 500 mg of metformin once daily for 3 months. Serum creatinine, blood urea nitrogen, high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein (LDL), cholesterol, triglyceride, fasting blood sugar, testosterone, 17-hydroxyprogesterone, and irisin were assayed in the studied groups. Circulating irisin was significantly higher in PCOS women. Circulating irisin levels correlated with 17-hydroxyprogesterone, testosterone, and insulin. Three months metformin treatment decreased circulating irisin in PCOS women and improved IR. Circulating irisin is directly associated with insulin resistance in PCOS women and may be used as a biomarker for IR in these patients. Moreover, metformin as a confounding therapy in metabolic diseases can be used to regulate circulating irisin levels in PCOS women.

An Overview of FGF19 and FGF21: The Therapeutic Role in the Treatment of the Metabolic Disorders and Obesity.

Fibroblast growth factors (FGFs) are responsible for the regulation of a wide range of biological functions, among which cellular proliferation, survival, migration, and differentiation could be pointed out. FGF19 controls the enterohepatic bile acid/cholesterol system, and FGF21 modulates fatty acid/glucose metabolism. Obesity, type 2 diabetes, coronary artery disease, and cancer, all can alter FGF21 circulating concentrations. In contrast to FGF21, metabolic diseases exhibit reduced serum FGF19 levels. Accordingly, FGF19 and FGF21 play important roles in regulating glucose and lipid metabolism. Hence, we present here a timely review on the relationship between FGF19/21 and metabolic diseases, especially obesity, and their probable role in development and treatment of obesity seems necessary.

Cadmium Testicular Toxicity in Male Wistar Rats: Protective Roles of Zinc and Magnesium.

Cadmium (Cd) is a highly toxic element, which may cause toxicity to most organs in the body. Zinc (Zn) and magnesium (Mg) are essential minerals with probable benefits on Cd harmful effects. Finding an efficient and non-pathological treatment against Cd toxicity seems promising. Fifty adult rats were divided into ten experimental groups of five rats each. The Cd group was treated with 1 mg Cd/kg and the control group received 0.5 cm3 normal saline. The other eight groups received Zn (0.5 and 1.5 mg/kg) and Mg (0.5 and 1.5 mg/kg) either alone or in combination with 1 mg Cd/kg through IP injection for 3 weeks. Testis malondialdehyde (MDA), sperm parameters, and testis histopathology were investigated. Cd reduced sperm parameters and increased testis MDA. Moreover, Cd exposure caused a significant histological damage in testis of male rats. However, Zn or Mg treatment prevented and reversed Cd toxic alterations in testis. These findings suggest that co-administration of Zn or Mg could improve cadmium testicular toxicity in male Wistar rats.

Protective Role of Zinc and Magnesium against Cadmium Nephrotoxicity in Male Wistar Rats.

Cd is a toxic metal that has a destructive impact on most organ systems. This work aims to determine Zn or Mg protective effects against Cd renal toxicity. In this study, rats were divided into six groups. The Cd group was treated with 1 mg Cd/kg, and the control group received 0.5 cm3 normal saline, intraperitoneally. The other four groups received one of the following dosages of 1 mg/kg Cd + 0.5 mg/kg Zn, 1 mg/kg Cd + 1.5 mg/kg Zn, 1 mg/kg Cd + 0.5 mg/kg Mg, or 1 mg/kg Cd + 1.5 mg/kg Mg through IP injection for 3 weeks. Kidney malondialdehyde (MDA) and serum sodium, potassium, urea, creatinine, and protein were measured. Light microscopic examination was used for histological studies. Cd reduced serum creatinine and protein, and increased urea, sodium, and potassium. Moreover, Cd exposure caused a significant enhancement in MDA levels as well as histological damage in kidneys. Zn or Mg treatment prevented and reversed toxic alterations induced by Cd. These results suggest that Zn and Mg may have protective effects against Cd renal toxicity.

Antioxidant effects of Citrus aurantifolia (Christm) juice and peel extract on LDL oxidation.

BACKGROUND: We studied the antioxidant effects of fresh juice and peel extract of Citrus aurantifolia (Christm). METHODS: Low density lipoprotein (LDL) was separated from one hypercholesterolemic human serum by modified Bronzert and Brewer procedure. Oxidation of LDL was measured at 234 nm against 0, 5, 10, 20, 25, 30 and 40 µl of fresh lime juice and 0, 5, 10, 15 and 20 µl of peel polyphenolic extract solution in DMSO. RESULTS: 5 µl of lime juice didn't change LDL oxidation. 10 µl of juice inhibited LDL oxidation, and with increasing the juice concentration, LDL was oxidized faster. The higher concentrations of peel extract prevented LDL oxidation better than the lower ones. CONCLUSIONS: Both juice and peel demonstrated antioxidant properties, but the excessive consumption of lime juice seems not to be beneficial. Regarding the intensity and type of flavonoids, lime juice and peel may show different effects.