Methods: A systematic literature search was done in health-related electronic databases. The search was limited to studies published in English until September 2017. We also checked the references of retrieved articles and relevant reviews for any additional studies. The methodological quality of the studies included in this review was assessed using the 'Scales for Quality Assessment'. The I2 test was used to quantify between-study heterogeneity. A value of I2 > 50% indicated substantial heterogeneity. For the pooled analysis, summary odds ratio (OR) and its 95% confidence interval (CI) in random effect model were used.
Results: Eight case-control studies (1192 cases with diabetic nephropathy and 2399 controls) met the inclusion criteria. Three groups of people namely Africans, Asians and Caucasians were included in this review. There were significant protective effects of SNP -819 C/T in overall population (OR 0.32, 95% CI 0.26-0.4) and - 1082 A/G SNP in the Asian population (OR 0.64, 95% CI 0.47-0.86) on diabetic nephropathy in the recessive model. There was no significant effect of -592 A/C on diabetic nephropathy.
Conclusion: The findings suggest the protective effects of -1082A/G and -819G/A polymorphisms on the risk of developing diabetic nephropathy in type 2 diabetes mellitus, especially in the Asian population. Well- designed, prospective studies with sufficient number of participants are recommended to substantiate these findings.
Methods: In this study, the region spanning exon 2 from the 4th to 18th codon within the peptide sequence of wtKRAS was chosen for sequence manipulation. Mutated G12V and G13D K-ras controls were generated in silico, along with additional single amino acid substitutions flanking the original codon 12/13 mutations. IEDB was used for assessing human and mouse MHC class I/II epitope predictions, as well as linear B-cell epitopes predictions, while RNA secondary structure prediction was performed via CENTROIDFOLD. A scoring and ranking system was established in order to shortlist top mimotopes whereby normalized and reducing weighted scores were assigned to peptide sequences based on seven immunological parameters. Among the top 20 ranked peptide sequences, peptides of three mimotopes were synthesized and subjected to in vitro and in vivo immunoassays. Mice PBMCs were treated in vitro and subjected to cytokine assessment using CBA assay. Thereafter, mice were immunized and sera were subjected to IgG-based ELISA.
Results: In silico immunogenicity prediction using IEDB tools shortlisted one G12V mimotope (68-V) and two G13D mimotopes (164-D, 224-D) from a total of 1,680 candidates. Shortlisted mimotopes were predicted to promote high MHC-II and -I affinities with optimized B-cell epitopes. CBA assay indicated that: 224-D induced secretions of IL-4, IL-5, IL-10, IL-12p70, and IL-21; 164-D triggered IL-10 and TNF-α; while 68-V showed no immunological responses. Specific-IgG sera titers against mutated K-ras antigens from 164-D immunized Balb/c mice were also elevated post first and second boosters compared to wild-type and G12/G13 controls.
Discussion: In silico-guided predictions of mutated K-ras T- and B-cell epitopes were successful in identifying two immunogens with high predictive scores, Th-bias cytokine induction and IgG-specific stimulation. Developments of such immunogens are potentially useful for future immunotherapeutic and diagnostic applications against KRAS(+) malignancies, monoclonal antibody production, and various other research and development initiatives.
MATERIALS AND METHODS: Six control and five DM Wistar rats were evaluated. DM was induced at 11 weeks of age using streptozotocin (STZ; 60 mg/kg, intraperitoneal). Animals were monitored up to 38 weeks of age, when plasma glucose, lipid profile, and markers specific for systemic inflammation, endothelial dysfunction, and oxidative stress were measured. The amount of fat within the aortic wall was assessed semiquantitatively using Oil Red O staining.
RESULTS: Diabetic rats presented significantly higher plasma glucose (p < 0.001), total cholesterol and triglycerides (both p = 0.02), high-sensitivity C-reactive protein (p = 0.01), and vascular endothelial growth factor (p = 0.04) levels, and significantly lower interleukin-10 (p = 0.04), superoxide dismutase (p < 0.01), and glutathione peroxidase (p = 0.01) levels than the control rats. Mild (grade 1) atherosclerotic lesions were observed in the aortic wall of 80% of the diabetic rats and in none of the control rats.
CONCLUSIONS: This study presents a STZ-induced type 1 DM rat model with one of the longest follow-ups in the literature. In this model, long-term DM created a highly pro-atherogenic environment characterised by hyperglycemia, dyslipidemia, systemic inflammation, endothelial dysfunction, and oxidative stress that resulted in the development of early aortic atherosclerotic lesions.
METHODS: Fifty-two patients with colorectal cancer were randomized at four weeks after surgery to receive either a placebo (n = 25) or 30 billion colony-forming unit (CFU) of a mixture of six viable strains including 107 mg of Lactobacillus acidophilus BCMC® 12,130, Lactobacillus lactis BCMC® 12,451, Lactobacillus casei subsp BCMC® 12,313, Bifidobacterium longum BCMC® 02120, Bifidobacterium bifidum BCMC® 02290 and Bifidobacterium infantis BCMC® 02129 (n = 27). Patients were instructed to take the product orally twice daily for six months. Infection status, diarrhea or hospital admission were recorded throughout the study. Blood was taken pre- and post-intervention to measure TNF-α, IFN-γ, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 using ELISA multiplex kit.
RESULTS: The majority of cases (~ 70%) were in Duke's C colorectal cancer for both groups. No surgical infection occurred and no antibiotics were required. Chemotherapy induced diarrhea was observed in both groups. Significant reduction in the level of pro-inflammatory cytokine, TNF-α, IL-6, IL-10, IL-12, IL-17A, IL-17C and IL-22 were observed in CRC patients who received probiotics as compared to pre-treatment level (P
METHODOLOGY: The present study was carried out to determine the role of TLR-4 on eliciting the immunomodulatory effects of recombinant BCG expressing MSP-1C of Plasmodium falciparum leading to the production of NO and IL-10, as well as the expression of iNOS. Six groups of mice (n = 6 per group) were immunised thrice, three weeks apart with intraperitoneal phosphate buffered saline T80 (PBS-T80), BCG or rBCG in the presence or absence of a TLR-4 inhibitor; TAK-242, given one hour prior to each immunisation. Peritoneal macrophages were harvested from the mice and cultured for the determination of NO, iNOS and IL-10 via Griess assay, ELISA and Western blot respectively.
RESULTS: The results showed significant inhibition of the production of NO and IL-10 and the expression of iNOS in all groups of mice in the presence of TAK-242.
CONCLUSIONS: These results presented evidence of the role of TLR-4/rBCG attachment mechanism in modulating the production of NO and IL-10 and the expression of iNOS in response to our rBCG-based malaria vaccine candidate expressing MSP-1C of P. falciparum.