Novel and very rare causative variants in the COL7A1 gene of Vietnamese patients with recessive dystrophic epidermolysis bullosa revealed by whole-exome sequencing.

BACKGROUND: Dystrophic epidermolysis bullosa (DEB) is a rare inherited disorder characterized by skin fragility leading to trauma-induced subepidermal blisters and healing with scarring. DEB is caused by mutations in COL7A1, the gene encoding for type VII collagen (COLVII). The DEB inheritance trait is divided into dominant dystrophic epidermolysis bullosa (DDEB) and recessive dystrophic epidermolysis bullosa (RDEB). METHODS: Whole-exome sequencing (WES) was performed for identifying mutations in six affected individuals of five Vietnamese families. RESULTS: Three novel variants in total of eight variants were found in five families. The first novel variant causing glycine substitution (c.8279G>A, p.G2760E), the remaining two novel variants resulted in splice site affecting (c.4518+2delT and c.5821-2A>G). Functional analysis indicated that the splice site at c.4518+2delT resulted in a skipping of exon 43, leading to an in-frame deletion of 12 amino acids. CONCLUSION: Our finding expands the spectrum of COL7A1 mutations and reports altered splicing at c.4518+2delT during the processing of the pre-mRNA. This study provides an additional scientific basis for diagnosis, genetic counseling, and prognosis purposes of EB patients.

Nutritional Status and Feeding Regimen of Patients with Esophagus Cancer-A Study from Vietnam.

BACKGROUND: Esophagus cancer patients are at high risk of malnutrition. This study was performed to assess the nutritional status and dietary intake of newly diagnosed esophageal cancer patients in Vietnam National Cancer Hospital (NCH). METHODS: A cross-sectional study was conducted on 206 early esophageal cancer inpatients after gastrostomy from September 2017 to June 2018. The chi-squared test, Fisher exact test, and Mann-Whitney test were performed. The software of the Vietnam National Institute of Nutrition was used to evaluate the dietary intake of patients. RESULTS: All the participants were male with a mean age of 57.1 ± 8.5 years. Overall, 87.4% of patients had dysphagia. Furthermore, 82.5% and 90.8% of patients reported weight loss one and six months pre-diagnosis, respectively. Moreover, 52.9% of patients suffered from mild/moderate malnutrition and 29.6% of patients had severe malnutrition according to the Patient-Generated Subjective Global Assessment (PG-SGA). The body mass index (BMI) and mid upper arm circumference (MUAC) measurement revealed 47.6% and 50% of undernourished patients, respectively. The proportions of patients having malnutrition were 10.7%, 55.8%, and 27.2% according to albumin, prealbumin, and total lymphocyte counts, respectively. The means of energy, protein, lipid, and carbohydrate in the patients' 24 h preoperative diets were 973.6 ± 443.0 kcal/day, 42.4 ± 21.6 g/day, 31.0 ± 15.5 g/day, and 130.0 ± 64.5 g/day. The total energy, total protein, animal protein, total lipid, and plant lipid in the dietary intake of patients were strongly correlated with age, economic classification, and PG-SGA (each p < 0.05). The total energy intake increased day by day, with the average energy intake of 1343.9 ± 521.3 kcal on the seventh day. Energy and protein response rates increased day by day and were highest at 7 days post-operation at 18.0% and 19.4%. CONCLUSION: Malnutrition and insufficient intake are noteworthy in esophageal cancer patients. The PG-SGA is strongly correlated with the dietary intake of patients. The results from this study will help medical staff to prevent malnutrition and improve the nutritional status of esophageal cancer inpatients. Furthermore, public awareness should be raised on recognizing weight loss as an early symptom of esophageal cancer and the utilization of preoperative assessment tools for nutritional assessment and malnutrition management.

Expression, Purification, and in vivo Evaluation of GFP-Fused M Cell Targeting Receptor Binding Domain of Protein FimH.

BACKGROUND: The number of oral vaccines is still limited due to many difficulties suffered in the intestinal environment, such as mucosal clearance, vast area, harsh conditions, deteriorative enzymes, impermeability, tolerance, etc. Numerous strategies have focused on directing antigen to the receptors of M cells, which is the main gateway to acquire and initiate specific responses to antigens in intestine. FimHrb is a receptor binding domain of type 1 of fimbriae from E. coli and Salmonella that can bind to GP2 receptor expressed exclusively on M cells. OBJECTIVE: In this study, we evaluated the potential of FimHrb for oral vaccine development via its ability to adhere M cells. METHODS: The coding gene of FimHrb fused Green Fluorescent Protein (GFP) was cloned and expressed intracellularly in E. coli host strain. The recombinant protein FimHrb-GFP was then purified by IMAC method through 6x His tag designed downstream of GFP. Finally, the purified protein was monitored its binding on murine M cells in Payer Patch region. RESULTS: Following the methods mentioned above, the coding gene FimHrb-GFP was successfully cloned into vector pET22b and intracellularly expressed in soluble form at low temperature induction. The purity and the recovered yield of this protein were 90% and 20%, respectively. After that, the adhesion of FimHrb-GFP was monitored in murine small intestine, which showed that the protein bound to Peyer Patch region and did not restrict on M cells. CONCLUSION: With the present data, we revealed a candidate protein FimHrb targeted receptor on M cells for oral vaccine development and other factors in E. coli would supplement FimH to provide the specific invasion of these bacteria via M cells.

Whole Genome Sequencing of a Vietnamese Family from a Dioxin Contamination Hotspot Reveals Novel Variants in the Son with Undiagnosed Intellectual Disability.

Although it has been a half-century since dioxin-contaminated herbicides were used to defoliate the landscape during the Vietnam War, dioxin contamination "hotspots" still remain in Vietnam. Environmental and health impacts of these hotspots need to be evaluated. Intellectual disability (ID) is one of the diseases found in the children of people exposed to the herbicides. This study aims to identify genetic alterations of a patient whose family lived in a dioxin hotspot. The patient's father had a highly elevated dioxin concentration. He was affected with undiagnosed moderate ID. To analyze de novo mutations and genetic variations, and to identify causal gene(s) for ID, we performed whole genome sequencing (WGS) of the proband and his parents. Two de novo missense mutations were detected, each one in ETS2 and ZNF408 genes, respectively. Compound heterozygosity was identified in CENPF and TTN genes. Existing knowledge on the genes and bioinformatics analyses suggest that EST2, ZNF408, and CENPF might be promising candidates for ID causative genes.

Ginsenoside Rh1: A Systematic Review of Its Pharmacological Properties.

Ginsenoside Rh1 is one of major bioactive compounds extracted from red ginseng, which has been increasingly used for enhancing cognition and physical health worldwide. The objective of this study was to review the pharmacological effects of ginsenoside Rh1 in a systematic manner. We performed searches on eight electronic databases including MEDLINE (Pubmed), Scopus, Google Scholar, POPLINE, Global Health Library, Virtual Health Library, the System for Information on Grey Literature in Europe, and the New York Academy of Medicine Grey Literature Report to select the original research publications reporting the biological and pharmacological effects of ginsenoside Rh1 from in vitro and in vivo studies regardless of publication language and study design. Upon applying the inclusion and exclusion criteria, we included a total of 57 studies for our systemic review. Ginsenoside Rh1 exhibited the potent characteristics of anti-inflammatory, antioxidant, immunomodulatory effects, and positive effects on the nervous system. The cytotoxic effects of ginsenoside Rh1 were dependent on different types of cell lines. Other pharmacological effects including estrogenic, enzymatic, anti-microorganism activities, and cardiovascular effects have been mentioned, but the results were considerably diverged. A higher quality of evidence on clinical trial studies is highly recommended to confirm the consistent efficacy of ginsenoside Rh1.