"Adipose-derived mesenchymal stem cell therapy for the management of female sexual dysfunction: Literature reviews and study design of a clinical trial".

Hormone imbalance and female sexual dysfunction immensely affect perimenopausal female health and quality of life. Hormone therapy can improve female hormone deficiency, but long-term use increases the risk of cardiovascular diseases and cancer. Therefore, it is necessary to develop a novel effective treatment to achieve long-term improvement in female general and sexual health. This study reviewed factors affecting syndromes of female sexual dysfunction and its current therapy options. Next, the authors introduced research data on mesenchymal stromal cell/mesenchymal stem cell (MSC) therapy to treat female reproductive diseases, including Asherman's syndrome, premature ovarian failure/primary ovarian insufficiency, and vaginal atrophy. Among adult tissue-derived MSCs, adipose tissue-derived stem cells (ASCs) have emerged as the most potent therapeutic cell therapy due to their abundant presence in the stromal vascular fraction of fat, high proliferation capacity, superior immunomodulation, and strong secretion profile of regenerative factors. Potential mechanisms and side effects of ASCs for the treatment of female sexual dysfunction will be discussed. Our phase I clinical trial has demonstrated the safety of autologous ASC therapy for women and men with sexual hormone deficiency. We designed the first randomized controlled crossover phase II trial to investigate the safety and efficacy of autologous ASCs to treat female sexual dysfunction in perimenopausal women. Here, we introduce the rationale, trial design, and methodology of this clinical study. Because aging and metabolic diseases negatively impact the bioactivity of adult-derived MSCs, this study will use ASCs cultured in physiological oxygen tension (5%) to cope with these challenges. A total of 130 perimenopausal women with sexual dysfunction will receive two intravenous infusions of autologous ASCs in a crossover design. The aims of the proposed study are to evaluate 1) the safety of cell infusion based on the frequency and severity of adverse events/serious adverse events during infusion and follow-up and 2) improvements in female sexual function assessed by the Female Sexual Function Index (FSFI), the Utian Quality of Life Scale (UQOL), and the levels of follicle-stimulating hormone (FSH) and estradiol. In addition, cellular aging biomarkers, including plasminogen activator inhibitor-1 (PAI-1), p16 and p21 expression in T cells and the inflammatory cytokine profile, will also be characterized. Overall, this study will provide essential insights into the effects and potential mechanisms of ASC therapy for perimenopausal women with sexual dysfunction. It also suggests direction and design strategies for future research.

Association of TP53 gene codon 72 polymorphism with Helicobacter pylori-positive non-cardia gastric cancer in Vietnam.

INTRODUCTION: This research aimed to determine the association of the combination of H. pylori infection and TP53 codon 72 polymorphism with non-cardia gastric cancer (GC) in Vietnam. METHODOLOGY: A total of 164 patients with non-cardia GC and 164 patients with peptic ulcer disease or functional dyspepsia in controls matched by sex and age were enrolled. H. pylori infection was diagnosed by rapid urease test and polymerase chain reaction (PCR). The cagA gene-positivity and vacA sm subtypes were determined by multiplex PCR. Genotypes of TP53 codon 72 polymorphism were determined by PCR-restriction fragment length polymorphism. RESULTS: The prevalence of H. pylori infection in GC and control group were 61.6% and 55.4%, respectively. The rates of cagA-positive strains in the two H. pylori-positive groups were 80.2% and 71.4%, respectively. There was no statistically significant difference in TP53 codon 72 genotype distribution between GC group (frequencies of Arg/Arg, Arg/Pro and Pro/Pro genotypes were 31.1%, 43.3% and 25.6%, respectively) and controls (29.3%, 52.4% and 18.3%, respectively), p = 0.172. The significant difference in genotype distribution was observed in recessive model (Pro/Pro vs Arg/Arg + Arg/Pro) when stratifying by H. pylori infection (OR = 2.02, 95% CI 1.03-3.96, p = 0.041) and by cagA-positivity (OR = 2.33, 95% CI 1.07-5.07, p = 0.032). CONCLUSIONS: This study suggests a synergistic interaction between H. pylori infection, especially cagA-positive H. pylori, and Pro/Pro genotype of TP53 codon 72 polymorphism might play a significant role in the pathogenesis of GC in the Vietnamese population.

Helicobacter pylori 23S rRNA gene mutations associated with clarithromycin resistance in chronic gastritis in Vietnam.

INTRODUCTION: Data about the prevalence of the A2142C, A2142G, and A2143G mutations in 23S rRNA gene is still limited. The aim of this study was to determine the prevalence of these mutations in 23S rRNA gene of H. pylori vietnamese strains. METHODOLOGY: One hundred and sixty-nine patients with H. pylori-positive chronic gastritis were examined. H. pylori was detected by rapid urease test and Polymerase chain reaction (PCR). Total DNA was extracted from gastric biopsy specimens. A2142C, A2142G, and A2143G mutations were detected by DNA sequencing and PCR-restriction fragment length polymorphism (PCR-RFLP). RESULTS: A2143G mutation was detected in 36.1% of samples, A2142G mutation in 3.6%, while A2142C mutation was not found in any case. The mixture of wild-type and mutation strains was found in 50% of specimens with A2142G, in 23% of specimens with A2143G mutation. There was no association of 23S rRNA gene point mutations with gender or age. However, an association between the heterogeneity of mutation and age was evidenced, with mean age of the group of pure A2143G higher than the group of wild-type/A2143G mixture, and rate of the wild-type/A2143G mixture higher in patients under 40 years of age. CONCLUSION: A2143G mutation was prominent, while A2142C mutation was not found in the 23S rRNA gene. PCR-RFLP has revealed a reliable assay allowing a rapid and cost-effective detection of clarithromycin-resistant strains. This is useful in countries as Vietnam with high prevalence of clarithromycin-resistance before choosing optimal therapy for H. pylori eradication.