Genetic polymorphisms in the miR-372 (rs12983273) and LncRNA HULC (rs7763881) genes and susceptibility to Hepatitis B virus (HBV) infection.

BACKGROUND: MicroRNAs (miRNAs) and Long non-coding RNAs (lncRNAs) are two major types of non-coding RNAs (ncRNAs) with regulatory roles. The initiation and progression of numerous diseases have been linked to genetic variation in miRNAs and lncRNAs. Many diseases, including hepatitis infection, are thought to be regulated by miRNA-LncRNA interactions. In this study, Single nucleotide polymorphisms (SNPs) in miR-372 (rs28461391 C/T) and HULC (rs7763881 A/C) were believed to play a role in HBV infection risk. METHODS AND RESULTS: Using the Polymerase chain reaction sequence-specific primer technique (PCR-SSP), 100 HBV patients and 100 healthy controls were genotyped for SNPs rs28461391 in miR-372 and rs7763881 in HULC. There was no significant difference in miR-372 rs12983273 genotype distribution between controls and HBV patients, according to our findings. On the other hand, there was a significant increase in HULC rs7763881 CC genotype (P < 0.05) coincides with a significant decrease in AC genotype distribution (P < 0.05) in HBV patients as compared to controls. Our results showed that the AA genotype is protective for HBV infection (OR 0.3; CI 0.13-9.07) while the CC genotype is associated with an increased risk of HBV infection (OR 3.43; CI 1.3-9.07). CONCLUSIONS: Our results suggest that HULC rs7763881 A/C might be a biomarker for HBV susceptibility. Larger sample studies are needed to confirm our preliminary data. To the best of our knowledge, the present study was the first to investigate the relevance of miR-372 (rs28461391 C/T) and HULC (rs7763881 A/C) gene polymorphisms to the risk of HBV infection in the Egyptian population.

Therapeutic potential of targeted-gold nanospheres on collagen-induced arthritis in rats.

Rheumatoid arthritis (RA) is a chronic inflammatory autoimmune disease that causes functional disability due to bone destruction and severe joint pain. Current anti-rheumatic treatments develop severe complications and do not provide complete remission. Gold nanoparticles (AuNPs) have garnered attention because of their unique physical and chemical properties. In this study, we have evaluated the therapeutic effects of gold nanospheres (AuNSs) with two different ligands (targeted-nanoparticles) against collagen-induced arthritis (CIA) and compared the outcomes with conventional methotrexate (MTX) and biological (infliximab) treatments. Clinical evaluation was performed by radiographic and histological examinations. The bioaccumulation of AuNSs in vital organs was assessed. The mechanistic studies targeting pro-inflammatory/anti-inflammatory and angiogenic mediators' expressions were performed. Radiographic examination showed that the targeted AuNSs reduced joint space narrowing and bone erosion. Moreover, histopathological examination of rat ankle joints demonstrated that targeted AuNSs reduce bone and cartilage degeneration/inflammation. Gold nanospheres-conjugated with nucleus localized peptide (nuclear membrane-targeted) (AuNSs@NLS) has resolved bone destruction and inflammation compared to gold nanospheres-conjugated at polyethylene glycol (AuNSs@PEG). Although the AuNSs accumulated in different organs in both cases, they did not induce any toxicity or tissue damage. The two different targeted AuNSs significantly suppress inflammatory and angiogenic mediators' expression and induced anti-inflammatory cytokine production, but the AuNSs@NLS had superior therapeutic efficacy. In conclusion, these results suggested that nuclear membrane-targeted AuNSs effectively attenuated arthritis progression without systemic side effects.

Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV / Associação entre polimorfismo do gene da interleucina-6 e regulação do ferro em pacientes em hemodiálise infectados pelo HCV

ABSTRACT Backgrounds: Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores. Method: To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP. Results: Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C. Conclusions: Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.

RESUMO Introdução: A hepcidina está associada à patogênese da anemia por insuficiência renal crônica, considerada um estado inflamatório crônico e também infecção por HCV. A IL-6 estimula a liberação de hepcidina a partir do fígado, suprime a captação intestinal de ferro e libera ferro das reservas internas. Método: Para detectar a associação entre o polimorfismo do gene IL-6 e os marcadores de anemia, 80 pacientes em hemodiálise (HD) [40 pacientes em HD, negativos para HCV; e 40 em HD, positivos para HCV] foram avaliados por exames químicos de rotina e hemograma completo, além da avaliação da hepcidina sérica, parâmetros do ferro [ferro sérico e ferritina sérica] e marcadores de hepatite C. O polimorfismo da IL-6 -174G/C foi determinado por MS-PCR, enquanto os polimorfismos de IL-6 -597G/A e -572 G/C foram detectados por PCR-SSP. Resultados: A hepcidina não esteve significativamente elevada em pacientes com HCV em comparação com pacientes em hemodiálise negativos para HCV. Uma diferença estatisticamente significativa foi detectada entre os pacientes em HD HCV negativos comparados aos positivos nas frequências de IL-6 -174 G/C e -597 G/A (P≤ 0,01 e P≤ 0,001, respectivamente). Por outro lado, foi relatada uma diferença não significativa entre pacientes em HD HCV negativos e positivos nas frequências de IL-6 -572 G/C. Conclusões: Nosso estudo indicou que os polimorfismos de IL-6 -174 G/C e -597 G/A podem desempenhar um papel na suscetibilidade ao HCV em pacientes em HD. Ainda necessitamos de estudos prospectivos adicionais em uma população maior para confirmar nossos achados.

Association between interleukin-6 gene polymorphism and iron regulation in hemodialysis patients infected with HCV.

BACKGROUNDS: Hepcidin is related to the pathogenesis of chronic renal failure anemia, which is considered a chronic inflammatory state as well as HCV infection. IL-6 stimulates the release of hepcidin from the liver, suppresses intestinal iron uptake, and releases iron from internal stores. METHOD: To detect the association between IL-6 gene polymorphism and anemia markers, 80 hemodialysis (HD) patients [40 negative HCV HD patients and 40 positive HCV HD patients] were studied by routine chemistry and complete blood count, in addition to the assessment of serum hepcidin, iron parameters [serum iron and serum ferritin], and hepatitis C markers. IL-6 polymorphism -174G/C was determined by MS-PCR, while IL-6 polymorphisms -597G/A and -572 G/C were detected by PCR-SSP. RESULTS: Hepcidin was non-significantly elevated in HCV-positive compared with HCV-negative hemodialysis patients. A statistically significant difference was detected between the negative and positive HCV HD patients in frequencies of IL-6 -174 G/C and -597 G/A (P≤ 0.01 and P≤ 0.001, respectively). On the other hand, a non-significant difference was reported between negative and positive HCV HD patients in the frequencies of IL-6 -572 G/C. CONCLUSIONS: Our study indicated that IL-6 -174 G/C and -597 G/A polymorphisms may play a role in HCV susceptibility in HD patients. Additional prospective studies on a larger population are needed to confirm our findings.

Gene polymorphism of transforming growth factor-ß1 in Egyptian patients with type 2 diabetes and diabetic nephropathy.

Role of the transforming growth factor-ß1 (TGF-ß1) gene polymorphisms located at codons 10 and 25 in the genetic predisposition to type 2 diabetes (T2D) and in diabetic nephropathy (DN) in Egyptian patients was investigated. A case control study was done for 99 unrelated Egyptian patients with T2D (50 DN(-) and 49 DN(+)) and 98 age- and sex-matched healthy controls. TGF-ß1 T869C (codon 10) and G915C (codon 25) polymorphism detection was done by amplification refractory mutation system method. DN(+) patients were younger, with higher body mass index, serum triglycerides, serum creatinine, and lower serum albumin than those in DN(-) patients. Moderate and bad grades of diabetic control were associated with DN (P < 0.001). The TGF-ß1 (T869C) C allele, TC and TC + CC genotypes were significantly higher in patients; the T allele and TT genotype were significantly higher in controls (Pc < 0.001). The TGF-ß1 TC genotype was associated with DN (Pc < 0.05). Non-significant differences were detected between T2D patients and controls in the frequencies of TGF-ß1 (G915C) alleles and genotypes. In conclusion, these preliminary data showed that the TGF-ß1 codon 10 C allele, and C allele-containing genotypes may be susceptible, and T allele/TT genotype may be protective factors for T2D and DN(+) complications.