Carrier screening for present disease prevalence and recessive genetic disorder in Taiwanese population.

Carrier screening is important to people have a higher prevalence of severe recessive or X-linked genetic conditions. This study is aimed that the frequency and uncertain nature of genetic variants was identified in Taiwanese population, providing individuals with information at risk of inherited diseases and their heritability to newborns. A total of 480 subjects receiving genetic counseling with no family history of inherited disorders were recruited into a cohort from 2018 to 2022. Next-generation sequencing (NGS) panel for autosomal dominant (AD), autosomal recessive (AR) and X-linked diseases was sequenced to assess disease prevalence and carrier frequency for the targeted diseases. Publicly available NGS datasets were analyzed following a tier-based system and ACMG recommendation. 5.3% of subjects showed the presence of variants for genetic disorder, and 2.3% of them were determined with AD. 14 of subjects with pathogenic variants were carriers for AR. The inherited genes were LDLR for AD disorders and AR disorders included GAA and ATP7B. 21.6% of subjects had highest carrier frequency of GJB2 gene. 0.5% of subjects had highest frequency of GJB6 for AR condition. In conclusions, the variants in LDLR, GAA and ATP7B genes were identified in Taiwanese population, indicating individuals had higher risk of Pompe disease, Wilson's disease and familial hypercholesterolemia. Taiwanese individuals carrying GJB2 and GJB6 had the considerable risk of hearing loss passing to their offspring.

Impact of maternal body mass index on outcomes of singleton pregnancies after assisted reproductive technology: a 14-year analysis of the US Nationwide Inpatient Sample.

BACKGROUND: Obesity is increasing globally, which affects multiple human functions, including reproductive health. Many women with overweight and obesity of child-bearing years are treated with assisted reproductive technology (ART). However, the clinical impact of body mass index (BMI) on pregnancy outcomes after ART remains to be determined. Therefore, this population-based retrospective cohort study aimed to assess whether and how higher BMI affects singleton pregnancy outcomes. METHODS: This study used the large nationally representative database of the US National Inpatient Sample (NIS), extracting data of women with singleton pregnancies who had received ART from 2005 to 2018. Diagnostic codes of the International Classification of Diseases, Ninth and Tenth edition (ICD-9 and ICD-10) were used to identify females admitted to US hospitals with delivery-related discharge diagnoses or procedures and secondary diagnostic codes for ART, including in vitro fertilization. The included women were further categorized into three groups based on BMI values < 30, 30-39, and ≥ 40 kg/m2. Univariate and multivariable regression analysis were conducted to assess the associations between study variables and maternal and fetal outcomes. RESULTS: Data of totally 17,048 women were included in the analysis, which represented a population of 84,851 women in the US. Number of women in the three BMI groups were 15, 878 (BMI < 30 kg/m2), 653 (BMI 30-39 kg/m2), and 517 (BMI ≥ 40 kg/m2), respectively. The multivariable regression analysis revealed that, compared to BMI < 30 kg/m2, BMI 30-39 kg/m2 was significantly associated with increased odds for pre-eclampsia and eclampsia (adjusted OR = 1.76, 95% CI = 1.35, 2.29), gestational diabetes (adjusted OR = 2.25, 95% CI = 1.70, 2.98), and Cesarean delivery (adjusted OR = 1.36, 95% CI = 1.15, 1.60). Further, BMI ≥ 40 kg/m2 was associated with greater odds for pre-eclampsia and eclampsia (adjusted OR = 2.25, 95% CI = 1.73, 2.94), gestational diabetes (adjusted OR = 3.64, 95% CI = 2.80, 4.72), disseminated intravascular coagulation (DIC) (adjusted OR = 3.79, 95% CI = 1.47, 9.78), Cesarean delivery (adjusted OR = 1.85, 95% CI = 1.54, 2.23), and hospital stay ≥ 6 days (adjusted OR = 1.60, 95% CI = 1.19, 2.14). However, higher BMI was not significantly associated with greater risk of the fetal outcomes assessed. CONCLUSIONS: Among US pregnant women who received ART, having a higher BMI level independently increases the risk for adverse maternal outcomes such as pre-eclampsia and eclampsia, gestational diabetes, DIC, longer hospital stays, and higher rates of Cesarean delivery, while risk is not increased for fetal outcomes.

Comparing the effects of two different progesterone vaginal gels, Progeson™ and Crinone™, from pharmacokinetics study to clinical applications in patients undergone fresh embryo transfer and frozen-thawed embryo transfer via natural cycle endometrial preparation protocol.

OBJECTIVE: The pharmacokinetics performance and clinical pregnancy rate of two vaginal progesterone gel, Progeson™ and Crinone™, were compared in this study. MATERIALS AND METHODS: In the pharmacokinetics performance, Progeson showed similar long-term dissolution rate as Crinone. In the clinical study, 141 subjects undergone in vitro fertilization (IVF) treatments were included to compare serum progesterone level and clinical pregnancy rates. RESULTS: Among the subjects, 78 subjects received fresh embryo transfer and 63 subjects received frozen embryo transfer via natural cycle endometrial preparation protocol. In each group, subjects were given either Crinone™ or Progeson™ for luteal phase support without combination with other progesterone products. The study showed that Crinone™ group led to higher estrogen level at mid-luteal phase in the fresh embryo transfer group, and Progeson™ group led to higher progesterone level at mid-luteal phase and pregnancy test day in the frozen-thawed embryo transfer group. CONCLUSION: Subjects received Crinone™ or Progeson™ had similar rate of pregnancy, live birth, and stillbirth in both fresh embryo transfer and frozen-thawed embryo transfer group. Thus, Progeson™ might be a suitable substitute for Crinone™ in assisted reproductive therapy.

Metastasis-associated in colon cancer-1 in gastric cancer: Beyond metastasis.

Metastasis-associated in colon cancer-1 (MACC1) is an oncogene that was first identified in colon cancer. The upstream and downstream of MACC1 form a delicate regulatory network that supports its tumorigenic role in cancers. Multiple functions of MACC1 have been discovered in many cancers. In gastric cancer (GC), MACC1 has been shown to be involved in oncogenesis and tumor progression. MACC1 overexpression adversely affects the clinical outcomes of GC patients. Regarding the mechanism of action of MACC1 in GC, studies have shown that it promotes the epithelial-to-mesenchymal transition and accelerates cancer metastasis. MACC1 is involved in many hallmarks of GC in addition to metastasis. MACC1 promotes vasculogenic mimicry (VM) via TWIST1/2, and VM increases the tumor blood supply, which is necessary for tumor progression. MACC1 also facilitates GC lymphangiogenesis by upregulating extracellular secretion of VEGF-C/D, indicating that MACC1 may be an important player in GC lymphatic dissemination. Additionally, MACC1 supports GC growth under metabolic stress by enhancing the Warburg effect. In conclusion, MACC1 participates in multiple biological processes inside and outside of GC cells, making it an important mediator of the tumor microenvironment.

Attenuated Salmonella typhimurium carrying shRNA-expressing vectors elicit RNA interference in murine bladder tumors.

AIM: To examine whether attenuated Salmonella typhimurium (S typhimurium) could be used as an anti-cancer agent or a tumor-targeting vehicle for delivering shRNA-expressing pDNA into cancer cells in a mouse tumor model. METHODS: Mouse bladder transitional cancer cell line (BTT-T739) expressing GFP was used, in which the GFP expression level served as an indicator of RNA interference (RNAi). BTT-T739-GFP tumor-bearing mice (4-6 weeks) were treated with S typhimurium carrying plasmids encoding shRNA against gfp or scrambled shRNA. The mRNA and protein expression levels of GFP were assessed 5 d after the bacteria administration, and the antitumor effects of S typhimurium were evaluated. RESULTS: In BTT-T739-GFP tumor-bearing mice, S typhimurium (1×10(9) cfu, po) preferentially accumulated within tumors for as long as 40 d, and formed a tumor-to-normal tissue ratio that exceeded 1000/1. S typhimurium carrying plasmids encoding shRNA against gfp inhibited the expression of GFP in tumor cells by 73.4%. Orally delivered S typhimurium significantly delayed tumor growth and prolonged the survival of tumor-bearing mice. CONCLUSION: This study demonstrates that attenuated S typhimurium can be used for both delivering shRNA-expressing vectors into tumor cells and eliciting RNAi, thus exerting anti-tumor activity, which may represent a new strategy for the treatment of solid tumors.