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1.
Dermatitis ; 2024 Apr 02.
Article in English | MEDLINE | ID: mdl-38563786

ABSTRACT

Background: Mutations in filaggrin (FLG), the gene that codes for the skin barrier protein, have been shown to be associated with atopic dermatitis (AD). Objective: The objectives of this study were to determine the effects of genetic counseling and parental education on infants at a high risk of AD. Methods: We enrolled 7521 newborns in Taiwan from January 1, 2016, to March 30, 2020, and all of them received genetic testing encompassing 20 known FLG mutations. The genetic counseling and AD prevention and care team consisted of pediatricians, dermatologists, social workers, and genetic counselors. The counseling was arranged for at least 30 minutes within 45 days after delivery. Results: A total of 2963 high-risk infants (39.4%) were identified. Homozygous c.1432C>T was the most commonly identified mutation. A total of 418 neonates' parents were stratified into counseling and noncounseling groups, where the effect of parental education was evaluated. The genetically stratified parental education program was effective in preventing AD development by 63.3% in high-risk infants before 12 months of life (P < 0.0001). Conclusion: Genetic stratification and parental education are effective in preventing the development of AD in high-risk infants before 12 months of life.

2.
Front Vet Sci ; 11: 1366759, 2024.
Article in English | MEDLINE | ID: mdl-38500606

ABSTRACT

Granulosa cells (GCs) are essential for follicular development, and long non-coding RNAs (LncRNAs) are known to support the maintenance of this process and hormone synthesis in mammals. Nevertheless, the regulatory roles of these lncRNAs within sheep follicular GCs remain largely unexplored. This study delved into the influence of a Loc105611671, on the proliferation and steroid hormone synthesis of sheep ovarian GCs and the associated target genes in vitro. Cell Counting Kit-8 (CCK-8) gain-of-function experiments indicated that overexpression of Loc105611671 significantly boosted GCs proliferation, along with estrogen (E2) and progesterone (P4) levels. Further mechanistic scrutiny revealed that Loc105611671 is primarily localized within the cytoplasm of ovarian granulosa cells and engages in molecular interplay with CDC42. This interaction results in the upregulation of CDC42 protein expression. Moreover, it was discerned that increased CDC42 levels contribute to augmented proliferation of follicular granulosa cells and the secretion of E2 and P4. Experiments involving co-transfection elucidated that the concurrent overexpression of CDC42 and Loc105611671 acted synergistically to potentiate these effects. These findings provide insights into the molecular underpinnings of fecundity in ovine species and may inform future strategies for enhancing reproductive outcomes.

3.
Phys Rev Lett ; 132(5): 056204, 2024 Feb 02.
Article in English | MEDLINE | ID: mdl-38364165

ABSTRACT

One-dimensional graphene superlattice subjected to strong Kronig-Penney (KP) potential is promising for achieving the electron-lensing effect, while previous studies utilizing the modulated dielectric gates can only yield a moderate, spatially dispersed potential profile. Here, we realize high KP potential modulation of graphene via nanoscale ferroelectric domain gating. Graphene transistors are fabricated on PbZr_{0.2}Ti_{0.8}O_{3} back gates patterned with periodic, 100-200 nm wide stripe domains. Because of band reconstruction, the h-BN top gating induces satellite Dirac points in samples with current along the superlattice vector s[over ^], a feature absent in samples with current perpendicular to s[over ^]. The satellite Dirac point position scales with the superlattice period (L) as ∝L^{ß}, with ß=-1.18±0.06. These results can be well explained by the high KP potential scenario, with the Fermi velocity perpendicular to s[over ^] quenched to about 1% of that for pristine graphene. Our study presents a promising material platform for realizing electron supercollimation and investigating flat band phenomena.

4.
J Med Genet ; 61(2): 176-181, 2024 Jan 19.
Article in English | MEDLINE | ID: mdl-37798098

ABSTRACT

BACKGROUND: Expanded genetic screening before conception or during prenatal care can provide a more comprehensive evaluation of heritable fetal diseases. This study aimed to provide a large cohort to evaluate the significance of expanded carrier screening and to consolidate the role of expanded genetic screening in prenatal care. METHODS: This multicentre, retrospective cohort study was conducted between 31 December 2019 and 21 July 2022. A screening panel containing 302 genes and next-generation sequencing were used for the evaluation. The patients were referred from obstetric clinics, infertility centres and medical centres. Genetic counsellors conducted consultation for at least 15 min before and after screening. RESULTS: A total of 1587 patients were screened, and 653 pairs were identified. Among the couples who underwent the screening, 62 (9.49%) had pathogenic variants detected on the same genes. In total, 212 pathogenic genes were identified in this study. A total of 1173 participants carried at least one mutated gene, with a positive screening rate of 73.91%. Among the pathogenic variants that were screened, the gene encoding gap junction beta-2 (GJB2) exhibited the highest prevalence, amounting to 19.85%. CONCLUSION: Next-generation sequencing carrier screening provided additional information that may alter prenatal obstetric care by 9.49%. Pan-ethnic genetic screening and counselling should be suggested for couples of fertile age.


Subject(s)
Counseling , Genetic Testing , Pregnancy , Female , Humans , Genetic Carrier Screening , Retrospective Studies , Prospective Studies
5.
Ann Med Surg (Lond) ; 85(5): 2056-2058, 2023 May.
Article in English | MEDLINE | ID: mdl-37228975

ABSTRACT

The incidence of ovarian tumors in pregnancy is around 0.05%. Primary ovarian cancer and metastatic malignancy are rare in pregnancy, and women often delayed in diagnosis. Importance: This is the first case ever reported on gastric cancer diagnosed during pregnancy presenting with a Krukenberg tumor and mimic ovarian tumor torsion, cholecystitis. By reporting this case, we could sensitize physicians to be more vigilance of abnormal abdominal pain in pregnant women. Case presentation: A 30-year-old female came to our hospital at the 30th week of gestational age due to preterm uterine contraction and worsening abdominal pain. A cesarean section was performed due to preterm uterine contraction and intolerable abdominal pain suspected to be ovarian torsion. Microscopic examination of the ovarian specimen showed signet-ring cells. The patient was diagnosed with gastric adenocarcinoma at stage IV after complete surveillance. Postpartum chemotherapy consisted of oxaliplatin and high-dose 5-fluorouracil. The patient died 4 months after delivery. Clinical discussion: Malignancies during pregnancy should be kept in mind while encountering atypical clinical presentations. Krukenburg tumor is rare in pregnancy and gastric cancer is the most common cause. Early diagnosis of the gastric cancer in the operable stage is the key to a better prognosis. Conclusion: Diagnostic examinations for gastric cancer in pregnancy could be performed after first trimester. Treatment should be introduced after balancing maternal-fetal risks. Early diagnosis and intervention are crucial to decrease the high mortality rate of gastric cancer in pregnancy.

6.
Mol Genet Genomic Med ; 11(7): e2174, 2023 07.
Article in English | MEDLINE | ID: mdl-37013606

ABSTRACT

BACKGROUND: The short arm of chromosome 16 consists of several copy number variants (CNVs) that are crucial in neurodevelopmental disorders; however, incomplete penetrance and diverse phenotypes after birth aggravate the difficulty of prenatal genetic counseling. METHODS: We screened 15,051 pregnant women who underwent prenatal chromosomal microarray analysis between July 2012 and December 2017. Patients with positive array results were divided into four subgroups based on the type of mutation identified on screening (16p13.3, 16p13.11, 16p12.2, and 16p11.2), and the maternal characteristics, prenatal examinations, and postnatal outcomes of different cases were reviewed. RESULTS: Chromosome 16 CNVs were identified in 34 fetuses, including four with 16p13.3 CNVs, 22 with 16p13.11 CNVs, two with 16p12.2 microdeletions, and six with 16p11.2 CNVs. Of the 34 fetuses, 17 delivered without early childhood neurodevelopmental disorders, three developed neurodevelopmental disorders during childhood, and 10 were terminated. CONCLUSION: Incomplete penetrance and variable expressivity make prenatal counseling challenging. Most cases with inherited 16p13.11 microduplication were reported to have normal development in early childhood, and we also report a few cases of de novo 16p CNVs without further neurodevelopmental disorders.


Subject(s)
Chromosome Disorders , Prenatal Diagnosis , Pregnancy , Child, Preschool , Humans , Female , Prenatal Diagnosis/methods , DNA Copy Number Variations , Chromosomes, Human, Pair 16/genetics , Chromosome Disorders/genetics , Fetus
7.
J Formos Med Assoc ; 122(8): 785-789, 2023 Aug.
Article in English | MEDLINE | ID: mdl-36907791

ABSTRACT

BACKGROUND: The rate of induction of labour has increased over the decades and numerous medications are available in the market. This study compares the efficacy and safety between dinoprostone slow-release pessary (Propess) and dinoprostone tablet (Prostin) for labour induction at term in nulliparous women. METHODS: This was a prospective single-blind randomized controlled trial conducted in a tertiary medical centre in Taiwan from September 1, 2020 to February 28, 2021. We recruited nulliparous women at term with a singleton pregnancy, fetus in cephalic presentation, an unfavourable cervix, and the cervical length had been measured by transvaginal sonography three times during labour induction. The main outcomes are duration from induction of labour to vaginal delivery, vaginal delivery rate, maternal and neonatal complication rates. RESULTS: In both groups, Prostin and Propess, 30 pregnant women were enrolled. The Propess group had higher vaginal delivery rate but it did not meet statistically significant difference. The Prostin group had significantly higher rate of adding oxytocin for augmentation (p = 0.0002). No significant difference was observed in either labouring course, maternal or neonatal outcomes. The probability of vaginal delivery was independently related to the cervical length measured by transvaginal sonography 8 h after Prostin or Propess administration as well as neonatal birth weight. CONCLUSION: Both Prostin and Propess can be used as cervical ripening agents with similar efficacy and without significant morbidity. Propess administration was associated with higher vaginal delivery rate and less need to add oxytocin. Intrapartum measurement of cervical length is helpful in predicting successful vaginal delivery.


Subject(s)
Dinoprostone , Oxytocics , Infant, Newborn , Pregnancy , Female , Humans , Oxytocin , Prospective Studies , Single-Blind Method , Labor, Induced
8.
Animals (Basel) ; 13(2)2023 Jan 09.
Article in English | MEDLINE | ID: mdl-36670776

ABSTRACT

CircRNAs are essential in regulating follicle growth and development and the female reproductive system at multiple levels. However, the molecular mechanism by which circRNAs regulate reproduction in sheep is unclear and requires further exploration. In this study, RNA sequencing was performed to reveal the circRNA expression profiles in the ovaries of Cele black sheep and Hetian sheep during estrus. Analysis of the number of circRNAs in their host genes revealed that 5031 genes could produce 20,835 circRNAs. Among the differentially expressed circRNAs (DEcircRNA), 75 were upregulated, and 105 were downregulated. Functional enrichment analysis showed that the host genes of DEcircRNA were involved in several pathways, including the MAPK and Hippo signaling pathway. In addition, we constructed a subnetwork of competitive endogenous RNA (ceRNA) containing 4 mRNAs, 4 microRNAs (miRNAs), and 10 circRNAs, potentially related to follicle development. Functional circRNAs (e.g., novel_circ_0003851, novel_circ_0015526, novel_circ_0008117) were found to act as ceRNAs for follicle growth and development-related mRNAs (CUEDC1, KPNB1, ZFPM2) by sponging functional miRNAs (miR-29a, miR-29b, miR-17-5p). Finally, through an RNA pull-down assay, oar-miR-125b was selected and confirmed as the target miRNA of novel-circ-0041512. We analyzed the overall expression of circRNAs in sheep ovaries. Further, we explored the potential mechanisms underlying the circRNA functions, providing a theoretical basis for the genetic progress of reproductive traits in sheep.

9.
Cells ; 13(1)2023 12 31.
Article in English | MEDLINE | ID: mdl-38201293

ABSTRACT

High levels of alcohol intake alter brain gene expression and can produce long-lasting effects. FK506-binding protein 51 (FKBP51) encoded by Fkbp5 is a physical and cellular stress response gene and has been associated with alcohol consumption and withdrawal severity. Fkbp5 has been previously linked to neurite outgrowth and hippocampal morphology, sex differences in stress response, and epigenetic modification. Presently, primary cultured Fkbp5 KO and WT mouse neurons were examined for neurite outgrowth and mitochondrial signal with and without alcohol. We found neurite specification differences between KO and WT; particularly, mesh-like morphology was observed after alcohol treatment and confirmed higher MitoTracker signal in cultured neurons of Fkbp5 KO compared to WT at both naive and alcohol-treated conditions. Brain regions that express FKBP51 protein were identified, and hippocampus was confirmed to possess a high level of expression. RNA-seq profiling was performed using the hippocampus of naïve or alcohol-injected (2 mg EtOH/Kg) male and female Fkbp5 KO and WT mice. Differentially expressed genes (DEGs) were identified between Fkbp5 KO and WT at baseline and following alcohol treatment, with female comparisons possessing a higher number of DEGs than male comparisons. Pathway analysis suggested that genes affecting calcium signaling, lipid metabolism, and axon guidance were differentially expressed at naïve condition between KO and WT. Alcohol treatment significantly affected pathways and enzymes involved in biosynthesis (Keto, serine, and glycine) and signaling (dopamine and insulin receptor), and neuroprotective role. Functions related to cell morphology, cell-to-cell signaling, lipid metabolism, injury response, and post-translational modification were significantly altered due to alcohol. In summary, Fkbp5 plays a critical role in the response to acute alcohol treatment by altering metabolism and signaling-related genes.


Subject(s)
Alcohol-Related Disorders , Ethanol , Female , Male , Animals , Mice , Ethanol/pharmacology , Lipid Metabolism , Injections , Alcohol Drinking , Glycine
10.
Front Microbiol ; 13: 993147, 2022.
Article in English | MEDLINE | ID: mdl-36160265

ABSTRACT

Acid rain not only has serious harm to the environment, but also has the same threat to plants, but the invasive plant Alternanthera philoxeroides still grows well compared to the native plant Alternanthera sessilis under acid rain stress. However, the underlying mechanism of resistance to the acid rain environment in invasive Alternanthera philoxeroides remains unclear. In the current study, we comparatively analyzed the plant physiological characteristics, soil physicochemical properties, and rhizosphere microbial communities of invasive A. philoxeroides and native A. sessilis under different pH condition. The simulated acid rain had a significant inhibitory effect on the morphological and physiological traits of A. philoxeroides and A. sessilis and reduced the soil nutrient content. However, A. philoxeroides was more tolerant of acid rain. Compared with CK, simulated acid rain treatment at pH 2.5 significantly increased the Chao1, ACE, and Shannon indexes of A. philoxeroides microorganisms. Under simulated acid rain treatment at pH 2.5, the fungal flora Chao1, ACE and Shannon index were significantly higher than those of CK by 14.5%, 12.4%, and 30.4%, respectively. The dominant bacterial phyla of soil bacteria were Proteobacteria, Actinobacteria, Bacteroidota, Actinobacteria, Firmicutes, Myxococcota, Chloroflexi, Patescibacteria, Gemmatimonadota, Verrucomicrobiota, and Armatimonadota. The dominant fungi were Ascomycota, Basidiomycota, Rozellomycota, and Olpidiomycota. The bacterial and fungal diversity and structure of A. philoxeroides and A. sessilis showed the greatest difference between the pH 2.5 treatment and CK. Redundancy analysis showed that electrical conductivity (EC) and total phosphorus (TP) were the main factors changing the bacterial communities, and available phosphorus (AP), organic matter (OM), EC, and pH were the main factors changing the fungal communities. This study contributes to the microbial community structure of the invasive plant A. philoxeroides and provides a theoretical basis for studying the invasion mechanism of invasive plants under acid rain.

11.
Taiwan J Obstet Gynecol ; 61(4): 652-656, 2022 Jul.
Article in English | MEDLINE | ID: mdl-35779916

ABSTRACT

OBJECTIVE: The transcription activator FOXM1 was found to be essential for beta cell expansion and glucose homeostasis during pregnancy in a mouse model. We assumed that the mechanism would be similar in humans. Thus, we aimed to determine the correlation, if any, between FOXM1 and gestational diabetes mellitus in pregnant women. MATERIALS AND METHODS: Participants were recruited and collected from a single tertiary medical center in Taiwan. Participants' maternal peripheral blood was retrieved upon their admission for labor. The postpartum cord blood was harvested within 5 min after delivery of the fetus to test the FOXM1 mRNA expression level, as well as glucose, insulin, and C-peptide protein concentrations. RESULT: We recruited 83 pregnant women, 63 without GDM and 20 with GDM. The non-GDM maternal samples had a FOXM1ΔCt of 9.2 ± 1.53, whereas it was 8.92 ± 1.48 in the GDM group (p = 0.504). In the cord blood group, the GDM and non-GDM FOXM1ΔCt were 7.7 ± 1.02 and 7.95 ± 1.56, respectively (p = 0.416). CONCLUSION: This is the first study to prove a relationship between FOXM1 and GDM in humans. Although the exact linear correlation is still unknown, our results may provide an impetus for further research.


Subject(s)
Diabetes, Gestational , Forkhead Box Protein M1 , Diabetes, Gestational/genetics , Diabetes, Gestational/metabolism , Female , Fetal Blood/chemistry , Fetal Blood/metabolism , Forkhead Box Protein M1/blood , Forkhead Box Protein M1/genetics , Forkhead Box Protein M1/metabolism , Glucose/metabolism , Humans , Insulin , Pregnancy
12.
Methods Enzymol ; 667: 775-812, 2022.
Article in English | MEDLINE | ID: mdl-35525561

ABSTRACT

Allelic series are extremely valuable genetic tools to study gene function and identify essential structural features of gene products. In mice, allelic series have been engineered using conventional gene targeting in embryonic stem cells or chemical mutagenesis. While these approaches have provided valuable information about the function of genes, they remain cumbersome. Modern approaches such as CRISPR-Cas9 technologies now allow for the precise and cost-effective generation of mouse models with specific mutations, facilitating the development of allelic series. Here, we describe procedures for the generation of three types of mutations used to dissect protein function in vivo using CRISPR-Cas9 technology. This step-by-step protocol describes the generation of missense mutations, large in-frame deletions, and insertions of genetic material using SCY1-like 1 (Scyl1) as a model gene.


Subject(s)
CRISPR-Cas Systems , Gene Editing , Animals , Gene Editing/methods , Gene Targeting , Mice , Mutagenesis , Technology
13.
J Formos Med Assoc ; 121(9): 1798-1803, 2022 Sep.
Article in English | MEDLINE | ID: mdl-35379575

ABSTRACT

BACKGROUND: Preterm premature rupture of membranes (PPROM) is one of the most common causes of preterm birth. Antibiotic treatment is recommended to prolong the pregnancy course and reduce fetal morbidity in women with PPROM. However, the guidelines for antibiotic selection are based on studies done years ago, mostly in Western countries, which may not reflect the geographic, temporal, and ethnic variation in microbial colonization and infection in other parts of the world. We aimed to understand whether the antibiotics recommended by the current guidelines were sufficient to eradicate the majority of pathogens involved. METHODS: This is a single-center retrospective study at a tertiary medical center in Taiwan with patients recruited from January 1, 2017, to December 31, 2019. All patient included had a confirmed diagnosis of PPROM. In this study, we aimed to investigate which broad-spectrum antibiotic was most suitable for PPROM cases in Taiwan. RESULTS: 133 women were included, and 121 women had positive culture results. Most of the pregnant women had one positive result (35.5%). The most common pathogen was Lactobacillus species (27.8%), followed by Streptococcus species (12.9%) and Staphylococcus species (12.09%). CONCLUSION: The most appropriate antibiotic therapy for PPROM was a combination of 1 g azithromycin given orally on admission plus a third-generation cephalosporin administered intravenously in the first 48 hours and followed by amoxicillin 500 mg per os for another five days. This recommended antibiotic regimen for women with PPROM needs further study under a randomized clinical trial with a larger study population to evaluate its efficacy.


Subject(s)
Fetal Membranes, Premature Rupture , Premature Birth , Anti-Bacterial Agents , Female , Humans , Infant, Newborn , Pregnancy , Retrospective Studies
14.
Stem Cell Reports ; 17(3): 522-537, 2022 03 08.
Article in English | MEDLINE | ID: mdl-35180394

ABSTRACT

Patients with coronavirus disease 2019 (COVID-19) commonly have manifestations of heart disease. Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) genome encodes 27 proteins. Currently, SARS-CoV-2 gene-induced abnormalities of human heart muscle cells remain elusive. Here, we comprehensively characterized the detrimental effects of a SARS-CoV-2 gene, Orf9c, on human pluripotent stem cell-derived cardiomyocytes (hPSC-CMs) by preforming multi-omic analyses. Transcriptomic analyses of hPSC-CMs infected by SARS-CoV-2 with Orf9c overexpression (Orf9cOE) identified concordantly up-regulated genes enriched into stress-related apoptosis and inflammation signaling pathways, and down-regulated CM functional genes. Proteomic analysis revealed enhanced expressions of apoptotic factors, whereas reduced protein factors for ATP synthesis by Orf9cOE. Orf9cOE significantly reduced cellular ATP level, induced apoptosis, and caused electrical dysfunctions of hPSC-CMs. Finally, drugs approved by the U.S. Food and Drug Administration, namely, ivermectin and meclizine, restored ATP levels and ameliorated CM death and functional abnormalities of Orf9cOE hPSC-CMs. Overall, we defined the molecular mechanisms underlying the detrimental impacts of Orf9c on hPSC-CMs and explored potentially therapeutic approaches to ameliorate Orf9c-induced cardiac injury and abnormalities.


Subject(s)
COVID-19/pathology , Coronavirus Nucleocapsid Proteins/genetics , Genome-Wide Association Study/methods , SARS-CoV-2/genetics , Action Potentials/drug effects , Adenosine Triphosphate/metabolism , Apoptosis/drug effects , Apoptosis/genetics , COVID-19/virology , Down-Regulation , Humans , Ivermectin/pharmacology , Meclizine/pharmacology , Myocytes, Cardiac/cytology , Myocytes, Cardiac/metabolism , Phosphoproteins/genetics , Pluripotent Stem Cells/cytology , Pluripotent Stem Cells/metabolism , Protein Interaction Maps/genetics , RNA, Messenger/chemistry , RNA, Messenger/metabolism , SARS-CoV-2/isolation & purification , Signal Transduction/genetics , Transcriptome/drug effects , Up-Regulation
15.
Heliyon ; 8(12): e12630, 2022 Dec.
Article in English | MEDLINE | ID: mdl-36619446

ABSTRACT

Despite tremendous advances in genome editing technologies, generation of conditional alleles in mice has remained challenging. Recent studies in cells have successfully made use of short artificial introns to engineer conditional alleles. The approach consists of inserting a small cassette within an exon of a gene using CRISPR-Cas9 technology. The cassette, referred to as Artificial Intron version 4 (AIv4), contains sequences encoding a splice donor, essential intronic sequences flanked by loxP sites and a splice acceptor site. Under normal conditions, the artificial intron is removed by the splicing machinery, allowing for proper expression of the gene product. Following Cre-mediated recombination of the two loxP sites, the intron is disabled, and splicing can no longer occur. The remaining intronic sequences create a frameshift and early translation termination. Here we describe the application of this technology to engineer a conditional allele in mice using Scyl1 as a model gene. Insertion of the cassette occurred in 17% of edited mice obtained from pronuclear stage zygote microinjection. Mice homozygous for the insertion expressed SCYL1 at levels comparable to wild-type mice and showed no overt abnormalities associated with the loss of Scyl1 function, indicating the proper removal of the artificial intron. Inactivation of the cassette via Cre-mediated recombination in vivo occurred at high frequency, abrogated SCYL1 protein expression, and resulted in loss-of-function phenotypes. Our results broaden the applicability of this approach to engineering conditional alleles in mice.

16.
Front Vet Sci ; 9: 1057282, 2022.
Article in English | MEDLINE | ID: mdl-36601328

ABSTRACT

Sheep exhibit a distinct estrous cycle that includes four different phases: proestrus, estrus, late estrus, and luteal phase. As the estrous cycle repeats, follicular development regularly alternates. We thus investigated ovarian transcriptome data from each of the four phases using weighted gene co-expression network analysis (WGCNA) to identify modules, pathways, and genes essential to follicle growth and development. We clustered mRNA and long non-coding RNA (lncRNA) into different modules by WGCNA, and calculated correlation coefficients between genes and Stages of the estrous cycle. Co-expression of the black module (cor = 0.81, P<0.001) and the yellow module (cor = 0.61, P<0.04) was found to be critical for follicle growth and development. A total of 2066 genes comprising the black and yellow modules was used for functional enrichment. The results reveal that these genes are mainly enriched in Cell cycle, PI3K-Akt signaling pathway, Oocyte meiosis, Apoptosis, and other important signaling pathways. We also identified seven hub genes (BUB1B, MAD2L1, ASPM, HSD3B1, WDHD1, CENPA, and MXI1) that may play a role in follicle development. Our study may provide several important new markers allowing in depth exploration of the genetic basis for multiparous reproduction in sheep.

17.
Cells ; 10(8)2021 08 19.
Article in English | MEDLINE | ID: mdl-34440898

ABSTRACT

BACKGROUND & AIMS: Liver fibrosis is a pathological healing process resulting from hepatic stellate cell (HSC) activation and the generation of myofibroblasts from activated HSCs. The precise underlying mechanisms of liver fibrogenesis are still largely vague due to lack of understanding the functional heterogeneity of activated HSCs during liver injury. Approach and Results: In this study, to define the mechanism of HSC activation, we performed the transcriptomic analysis at single-cell resolution (scRNA-seq) on HSCs in mice treated with carbon tetrachloride (CCl4). By employing LRAT-Cre:Rosa26mT/mG mice, we were able to isolate an activated GFP-positive HSC lineage derived cell population by fluorescence-activated cell sorter (FACS). A total of 8 HSC subpopulations were identified based on an unsupervised analysis. Each HSC cluster displayed a unique transcriptomic profile, despite all clusters expressing common mouse HSC marker genes. We demonstrated that one of the HSC subpopulations expressed high levels of mitosis regulatory genes, velocity, and monocle analysis indicated that these HSCs are at transitioning and proliferating phases at the beginning of HSCs activation and will eventually give rise to several other HSC subtypes. We also demonstrated cell clusters representing HSC-derived mature myofibroblast populations that express myofibroblasts hallmark genes with unique contractile properties. Most importantly, we found a novel HSC cluster that is likely to be critical in liver regeneration, immune reaction, and vascular remodeling, in which the unique profiles of genes such as Rgs5, Angptl6, and Meg3 are highly expressed. Lastly, we demonstrated that the heterogeneity of HSCs in the injured mouse livers is closely similar to that of cirrhotic human livers. CONCLUSIONS: Collectively, our scRNA-seq data provided insight into the landscape of activated HSC populations and the dynamic transitional pathway from HSC to myofibroblasts in response to liver injury.


Subject(s)
Hepatic Stellate Cells/metabolism , Liver/metabolism , Animals , Cells, Cultured , Male , Mice , Mice, Inbred C57BL , Principal Component Analysis , Single-Cell Analysis , Transcriptome/genetics
19.
J Formos Med Assoc ; 120(8): 1635-1641, 2021 Aug.
Article in English | MEDLINE | ID: mdl-33581963

ABSTRACT

PURPOSE: To evaluate the effectiveness of adding carbetocin to regular uterotonic agents for prevention of postpartum hemorrhage (PPH) after cesarean section for twin pregnancies. METHODS: This is a retrospective uncontrolled before-after study done in a tertiary center in Taiwan, 2010-2017. Women with twin pregnancies that underwent cesarean section were enrolled. The control group (n = 114) received oxytocin infusion and direct uterine injection. In addition to these, the study group (n = 127) received 100ug of intravenous carbetocin. Primary endpoint was the change in hemoglobin. Secondary endpoints included risk of PPH and undiagnosed PPH (Hb dropped more than 2 g/dL), blood loss, the need for additional uterotonic maneuvers, and blood transfusion. Hemodynamic changes were also investigated. RESULTS: After adjusting for confounding factors, the change in Hb (0.35 g/dL, 95% CI: -0.03∼0.74) and incidence of PPH (OR 0.30, 95% CI: 0.03∼3.28) were comparable in both groups. However, women with undiagnosed PPH decreased (OR 0.43, 95% CI:0.22∼0.85). Total blood loss in 24 h after delivery also decreased (-40.33 mL, 95%CI: -80.32∼ -0.34). The use of extra uterotonic medications and the need for blood transfusion did not differ. The systolic blood pressure 4 h after childbirth was higher in the carbetocin group (6.71, 95% CI: 2.27∼11.15). CONCLUSION: The use of carbetocin in addition to regular uterotonic agents decreased total blood loss and undiagnosed PPH. Also, systolic blood pressure 4 h after childbirth is higher in the carbetocin group. There was no significant difference in hemoglobin change and risk of PPH.


Subject(s)
Oxytocics , Oxytocin , Cesarean Section , Controlled Before-After Studies , Female , Humans , Oxytocics/therapeutic use , Oxytocin/analogs & derivatives , Pregnancy , Pregnancy, Twin , Retrospective Studies , Taiwan
20.
Ann Med Surg (Lond) ; 60: 146-148, 2020 Dec.
Article in English | MEDLINE | ID: mdl-33145023

ABSTRACT

PURPOSE: Vaginal cuff dehiscence with evisceration was defined as expulsion of intraperitoneal organs through the separated incision. Prolapsed epiploica of the colon is a rare complication after hysterectomy. The most common organ to prolapsed out from the dehiscence vaginal cuff is terminal ileum. We reported the first known case of prolapsed epiploica of the colon after robotic hysterectomy. CASE: This is a case who had prolapse of a vaginal tumor after sexual intercourse 5 months after robotic hysterectomy. Vaginal tumor resection and primary closure were performed successfully without complications. The final pathology revealed fat prolapse with foreign body reaction and confirmed prolapse of epiploica of the colon. Being aware of the risk factors and patients who are more likely to develop this complication is essential in making the correct diagnosis in time. MAJOR CONCLUSION: Patients with a higher risk of vaginal cuff dehiscence are advised to avoid sexual activity for a longer period of time. Surgical intervention is the primary treatment. Prolapsed epiploica of the colon should be kept in mind for those who have undergone hysterectomy in order to provide appropriate treatment in time.

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