Paediatric Asthma and the Microbiome: A Systematic Review.

Evidence from the literature suggests an association between the microbiome and asthma development. Here, we aimed to identify the current evidence for the association between asthma and the upper airway, lower airway and/or the gut microbiome. An electronic systemic search of PubMed, EBSCO, Science Direct and Web of Science was conducted until February 2022 to identify the eligible studies. The Newcastle-Ottawa Scale and the Systematic Review Centre for Laboratory Animal Experimentation risk of the bias tools were used to assess quality of included studies. Twenty-five studies met the inclusion criteria. Proteobacteria and Firmicutes were identified as being significantly higher in the asthmatic children compared with the healthy controls. The high relative abundance of Veillonella, Prevotella and Haemophilus in the microbiome of the upper airway in early infancy was associated with a higher risk of asthma development later in life. The gut microbiome analyses indicated that a high relative abundance of Clostridium in early childhood might be associated with asthma development later in life. The findings reported here serve as potential microbiome signatures associated with the increased risk of asthma development. There is a need for large longitudinal studies to further identify high-risk infants, which will help in design strategies and prevention mechanisms to avoid asthma early in life.

Hepatitis C virus, insulin resistance, and diabetes: A review.

Hepatitis C virus (HCV) infection and diabetes mellitus (DM) are two chronic diseases that are a cause of significant health and economic burdens worldwide. HCV is associated with the development of insulin resistance (IR) and DM. The mechanisms through which HCV induces IR and DM include direct viral effects, proinflammatory cytokines, and other immune-mediated processes. Type 1 DM (T1DM) and type 2 DM (T2DM) are both chronic diseases that involve impaired glucose homeostasis, albeit through different mechanisms. T1DM is an autoimmune disease that leads to the destruction of pancreatic beta cells resulting in insulin deficiency. In T2DM, a combination of peripheral IR and irregular production of insulin eventually leads to beta-cell destruction and insulin insufficiency. Both T1DM and T2DM etiologies involve a combination of genetic and environmental factors. The data on HCV and T1DM association remain limited, unlike T2DM, where a large body of evidence linking HCV to T2DM is available. Here, we intend to outline the current state of knowledge on HCV, IR, and DM.

SPCS1-Dependent E2-p7 processing determines HCV Assembly efficiency.

Recent studies identified signal peptidase complex subunit 1 (SPCS1) as a proviral host factor for Flaviviridae viruses, including HCV. One of the SPCS1's roles in flavivirus propagation was attributed to its regulation of signal peptidase complex (SPC)-mediated processing of flavivirus polyprotein, especially C-prM junction. However, whether SPCS1 also regulates any SPC-mediated processing sites within HCV polyprotein remains unclear. In this study, we determined that loss of SPCS1 specifically impairs the HCV E2-p7 processing by the SPC. We also determined that efficient separation of E2 and p7, regardless of its dependence on SPC-mediated processing, leads to SPCS1 dispensable for HCV assembly These results suggest that SPCS1 regulates HCV assembly by facilitating the SPC-mediated processing of E2-p7 precursor. Structural modeling suggests that intrinsically delayed processing of the E2-p7 is likely caused by the structural rigidity of p7 N-terminal transmembrane helix-1 (p7/TM1/helix-1), which has mostly maintained membrane-embedded conformations during molecular dynamics (MD) simulations. E2-p7-processing-impairing p7 mutations narrowed the p7/TM1/helix-1 bending angle against the membrane, resulting in closer membrane embedment of the p7/TM1/helix-1 and less access of E2-p7 junction substrate to the catalytic site of the SPC, located well above the membrane in the ER lumen. Based on these results we propose that the key mechanism of action of SPCS1 in HCV assembly is to facilitate the E2-p7 processing by enhancing the E2-p7 junction site presentation to the SPC active site. By providing evidence that SPCS1 facilitates HCV assembly by regulating SPC-mediated cleavage of E2-p7 junction, equivalent to the previously established role of this protein in C-prM junction processing in flavivirus, this study establishes the common role of SPCS1 in Flaviviridae family virus propagation as to exquisitely regulate the SPC-mediated processing of specific, suboptimal target sites.

Can Fasting Blood Sugar be Used as an Indicator of Long-Term Diabetic Control Instead of Estimated Average Glucose?

BACKGROUND: Diabetes mellitus is a chronic illness that is a worldwide issue. HbA1c has been used to monitor glycemic control in patients with diabetes for many years. Although HbA1c measurement is needed for calculating estimated average blood glucose (eAG), it is now recommended that eAG is used instead of HbA1c for expression of blood glucose control and communication with patients and health care providers. This study, investigated fasting blood glucose (FBS) as an indicator of overall chronic blood sugar control by assessing the correlation between FBS with eAG derived from HbA1c. METHODS: The blood samples for HbA1c assay were collected in EDTA tubes and were analyzed by an HPLC analyzer (G8 Tosoh, Japan). Blood samples for FBS were collected in serum separator tubes, transported, and centrifuged for 15 minutes at 3,000 g. FBS levels were determined in serum samples with the enzymatic hexokinase method by a clinical chemistry analyzer (Architect 8000, Abbott, USA). RESULTS: Statistical analysis was performed on 1,740 patients with type 2 diabetes mellitus with HbA1c levels above 6.5 mmol/L. The difference between FBS (9.3 ± 3.7 mmol/L) and eAG (11.14 ± 2.7 mmol/L) was statistically signif-icant (p < 0.0001). The correlation coefficient between FBS and eAG was r = 0.65 (95% CI; 0.62 - 0.69), with a p-value < 0.0001. While the correlation coefficient between FBS and eAG at HbA1c < 6.5% was r = 0.251 (95% CI, 0.16 - 0.34), with a significant p-value of < 0.00001. The combined data, standard deviation (SD), median, and interquartile range of eAG and FBS for all of the diabetic groups (n = 2,315), were 10.1 ± 3.00 mmol/L, 9.5 mmol/L, and 7.75 - 12.03 mmol/L for eAG, respectively. Similarly, these values were 8.5 ± 3.6 mmol/L, 7.5 mmol/L, and 6.0 - 10.00 mmol/L for FBS, respectively. CONCLUSIONS: We concluded that there is a moderate and significant positive correlation between fasting blood sugar and the estimated average blood glucose derived from HbA1c. Although FBS might be helpful for daily monitoring of diabetes. Further studies must be conducted to provide solid results to support that FBS and its derived variable eAG can replace HbA1c as an indicator of long-term overall control of T2DM patients.

Delayed by Design: Role of Suboptimal Signal Peptidase Processing of Viral Structural Protein Precursors in Flaviviridae Virus Assembly.

The Flaviviridae virus family is classified into four different genera, including flavivirus, hepacivirus, pegivirus, and pestivirus, which cause significant morbidity and mortality in humans and other mammals, including ruminants and pigs. These are enveloped, single-stranded RNA viruses sharing a similar genome organization and replication scheme with certain unique features that differentiate them. All viruses in this family express a single polyprotein that encodes structural and nonstructural proteins at the N- and C-terminal regions, respectively. In general, the host signal peptidase cleaves the structural protein junction sites, while virus-encoded proteases process the nonstructural polyprotein region. It is known that signal peptidase processing is a rapid, co-translational event. Interestingly, certain signal peptidase processing site(s) in different Flaviviridae viral structural protein precursors display suboptimal cleavage kinetics. This review focuses on the recent progress regarding the Flaviviridae virus genus-specific mechanisms to downregulate signal peptidase-mediated processing at particular viral polyprotein junction sites and the role of delayed processing at these sites in infectious virus particle assembly.