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Biomedical subjects

Sai Ma

Publications and source records attributed to Sai Ma.

13 recordsLinked to original sources

Deoxyribonucleic acid methylation abnormalities at imprinted loci in oligospermic and azoospermic men.

OBJECTIVE: To assess deoxyribonucleic acid (DNA) methylation at imprinted and repetitive genomic regions in ejaculated and testicular sperm from men with oligospermia, azoospermia, and those undergoing vasectomy reversal (VR), compared with fertile controls. DESIGN: Observational case-control study. SUBJECTS: Samples were obtained from 68 men, including 29 infertile men (18 oligospermic [5-15 million/mL], 11 severely oligospermic [<5 million/mL]) and 20 fertile controls with confirmed natural conceptions. Testicular tissue was collected from 11 azoospermic men (7 obstructive azoospermia [OA], 4 nonobstructive azoospermia [NOA]) and 8 men with prior paternity undergoing VR. EXPOSURE: Sperm DNA methylation at four imprinted genes (H19, GTL2, MEST, and LIT1) and one repetitive element (LINE1). MAIN OUTCOME MEASURES: Methylation levels at CpG sites determined by bisulfite pyrosequencing. RESULTS: The H19 was significantly hypomethylated only in severe oligospermia compared with fertile controls, whereas other groups showed nonsignificant trends with overlapping distributions. In contrast, MEST was significantly hypermethylated in oligospermic, azoospermic, and VR groups compared with fertile controls. No significant differences were observed for GTL2, LIT1, or LINE1. CONCLUSION: The DNA methylation abnormalities in sperm are locus-specific and vary across infertility phenotypes. MEST alterations were consistent across groups, whereas H19 changes were limited to severe oligospermia. Similar methylation patterns in testicular sperm from azoospermic and VR groups suggest that epigenetic alterations may reflect the testicular environment or obstruction, or differences between testicular and ejaculated sperm.

Humans↗

A single-cell spatial transcriptomic census of human skin anatomy.

The skin is the largest human organ and a site of significant disease burden, yet its cellular and molecular organization across the body are largely undefined. Here, we construct a spatially-resolved single-cell atlas of 1.2 million cells from normal adult human skin to localize 45 cell types across 15 anatomic sites. We define principles of organ-wide cell composition, including axes of cell diversity and specialization, and distinguish site-enriched cell types. Each body site is comprised of 10 multicellular neighborhoods that define cell-cell communication. Notably, we identify a perivascular neighborhood enriched for immune-stromal crosstalk with features resembling a homeostatic immune niche similar to skin-associated lymphoid tissue. Finally, mapping these neighborhoods onto skin disease reveals pathogenic neighborhood disruptions, including pan-disease immune alterations in the perivascular neighborhood. We present a framework charting the skin's multiscale spatial organization across a molecular to macroanatomic scale. This work advances our understanding of organ-wide skin cellular organization and communication, and its architectural disruption in disease.

Journal Article↗

HBO1 functions as an epigenetic barrier to hepatocyte plasticity and reprogramming during liver injury.

Hepatocytes can reprogram into biliary epithelial cells (BECs) during liver injury, but the underlying epigenetic mechanisms remain poorly understood. Here, we define the chromatin dynamics of this process using single-cell ATAC-seq and identify YAP/TEAD activation as a key driver of chromatin remodeling. An in vivo CRISPR screen highlights the histone acetyltransferase HBO1 as a critical barrier to reprogramming. HBO1 is recruited by YAP to target loci, where it promotes histone H3 lysine 14 acetylation (H3K14ac) and engages the chromatin reader zinc-finger MYND-type containing 8 (ZMYND8) to suppress YAP/TEAD-driven transcription. Loss of HBO1 accelerates chromatin remodeling, enhances YAP binding, and enables a more complete hepatocyte-to-BEC transition. Our findings position HBO1 as an epigenetic brake that restrains YAP-mediated reprogramming, suggesting that targeting HBO1 may enhance hepatocyte plasticity for liver regeneration.

Hepatocytes↗

Off-line comprehensive two-dimensional high-performance liquid chromatography system with size exclusion column and reverse phase column for separation of complex traditional Chinese medicine Qingkailing injection.

A comprehensive two-dimensional liquid chromatography system was constructed on the combination of size exclusion chromatography (SEC) and reverse phase liquid chromatography (RPLC). The first dimension used a SEC column with 300 mm x 8mm i.d., packed with Toyopearl HW-40S. The column was eluted with 0.05 mol/l Tris-HCl (pH 6.9) at a flow rate of 0.4 ml/min. The second dimension used a RPLC column with 100 mm x 4.6mm i.d., which was operated in gradient form at a flow rate of 1.0 ml/min. An automatic switching valve was used to collect the effluent of the SEC column every 3 min, and the effluent was automatically injected into the RPLC column. Mass spectrometer was used for peak identification. This system was used to separate Qingkailing injection, a traditional Chinese medicine (TCM). The result showed that the total peak capacity of this system could reach 1134 and the qualitative analysis of seven chemical components of the Qingkailing injection was accomplished by this system. The results show that comprehensive two-dimensional liquid chromatography system is of great importance and high value in the separation of complex TCM.

Chromatography, High Pressure Liquid↗

Impact of assisted hatching on the outcome of intracytoplasmic sperm injection: a prospective, randomized clinical trial and pregnancy follow-up.

OBJECTIVE: To evaluate the overall effect of assisted hatching (AH) on the implantation, pregnancy, and live birth rates in women undergoing intracytoplasmic sperm injection (ICSI) cycles; and to determine the effect of AH on the cytogenetic outcome (chromosomal constitution) of pregnancy. DESIGN: Prospective, randomized study. SETTING: Academic research environment. PATIENT(S): A total of 172 couples were enrolled in the study. INTERVENTION(S): Assisted hatching was carried out on day-3 ICSI embryos. MAIN OUTCOME MEASURE(S): Implantation, clinical pregnancy, and live birth rates; cytogenetic analysis of abortuses and umbilical cord blood samples from newborns. RESULT(S): Biochemical, clinical, and ongoing pregnancy rates were not significantly different between the AH and control groups. The implantation rate was higher in the AH group than in the control group (16% vs. 8%), especially in women aged > or =35 years. Postnatal umbilical cord blood samples were collected and cytogenetically analyzed from 39 live births (20 from the AH group, 19 from the control group). Two abnormal karyotypes were found (one AH, one control). There were seven spontaneous losses during the study interval. Six of the abortuses underwent cytogenetic study (five AH, one control), and four were found to have an abnormal karyotype (three AH, one control). CONCLUSION: We found that AH improves implantation rates of ICSI cycles and seems to be most effective in women aged > or =35 years. A larger sample size is needed to determine whether AH improves the take-home-baby rate. Assisted hatching did not affect the rate of chromosomal abnormalities in live births in this study.

Adult↗

Investigation of confined placental mosaicism (CPM) at multiple sites in post-delivery placentas derived through intracytoplasmic sperm injection (ICSI).

Although earlier studies on pregnancies derived through intracytoplasmic sperm injection (ICSI) reported increased non-mosaic aneuploidy among ICSI children, undetected mosaicism, such as confined placental mosaicism (CPM) has not been evaluated. We investigated the incidence of CPM in post-delivery placentas derived from ICSI, evaluated whether CPM was increased and whether it was a contributing factor to negative pregnancy outcome. [Fifty-one post-delivery placentas were collected from patients who underwent ICSI with a normal or negative pregnancy outcome]. Trophoblast and chorionic stroma from three sites were analyzed by comparative genomic hybridization (CGH) and flow cytometry. Detected abnormalities were confirmed by fluorescence in situ hybridization (FISH). The incidence of CPM in the ICSI population was compared to the general population from published data. We detected three cases of CPM in our study. One abnormality was found by CGH analysis; partial trisomy 7q and a partial monosomy Xp limited to the trophoblast at two sites. The abnormality was associated with a child affected by spina bifida. Two cases of mosaic tetraploidy were observed by flow cytometry in pregnancies with a normal outcome. All three abnormalities were confirmed by FISH analysis. The incidence of CPM in the ICSI study population was 5.88% (3/51), which was not statistically different from published reports in the general population (5.88% (42/714), Chi square, P > 0.05). The post-ICSI population was not at risk for CPM in this study.

Adult↗

Analysis of early meiotic events and aneuploidy in nonobstructive azoospermic men: a preliminary report.

OBJECTIVE: To study the events of spermatogenesis in azoospermic men by examining meiosis I spermatocytes and postmeiotic spermatozoa. DESIGN: A preliminary analysis of synaptonemal complex (SC), recombination, and chromosomal constitution (meiotic and postmeiotic) in testicular tissue. SETTING: Academic research environment. PATIENT(S): Three men with nonobstructive azoospermia and one fertile man (vasectomy reversal: control) who underwent testicular sperm extraction in preparation for intracytoplasmic sperm injection (ICSI). INTERVENTION(S): Testicular tissue specimens were processed by immunofluorescence analysis with antibodies against proteins associated with SC and recombination events. Fluorescence in situ hybridization (FISH) for chromosomes X, Y, and 18 was done on spermatocytes in prophase I and on postmeiotic spermatozoa. MAIN OUTCOME MEASURE(S): SC formation and recombination in meiosis I, aneuploidy. RESULT(S): The number of autosomal recombination foci in each patient was not statistically significantly different from control. The frequencies of XY bivalents with at least one recombination focus were statistically similar in the patients and control (74.2% vs. 82.6%, respectively). All observed cells in pachytene had normal XY constitutions. In spite of this, the rate of sex-chromosome aneuploidy in spermatozoa was statistically significantly higher in the patients compared with the control (1.89% vs. 0.83%). CONCLUSION(S): The combination of immunocytologic technology with FISH can add a level of precision in etiologic investigations of severe male factor infertility: men can have normal pairing and recombination but still yield aneuploid spermatozoa.

Adult↗

U50,488H depresses pulmonary pressure in rats subjected to chronic hypoxia.

In this study, we determined the effect of U50,488H (a selective kappa-opioid receptor agonist) on pulmonary artery in rats and investigated its prevention and treatment effects on hypoxic pulmonary hypertension (HPH). Isolated pulmonary arterial rings were superfused and the tension of the vessel was measured. The model of HPH was developed and indexes for hemodynamics and right ventricular hypertrophy were measured. We found that U50,488H relaxed the pulmonary artery rings in a dose-dependent manner and the effect was abolished by nor-binaltorphimine, a selective kappa-opioid receptor antagonist. Intravenous administration of U50,488H significantly lowered mean pulmonary artery pressure (mPAP) in normal rats and this effect was also abolished by nor-binaltorphimine. Hypoxia induced severe HPH in rats and intraperitoneal administration of U50,488H (every other day) during chronic hypoxia reduced mPAP and attenuated right ventricular hypertrophy compared with the control group. Moreover, acute intravenous administration of U50,488H after the rats subjected to chronic hypoxia for 4 weeks significantly lowered mPAP. Thus, U50,488H has significant vasorelaxant effect in rat pulmonary artery and has certain preventive and therapeutic application in HPH.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

A systematic review of relations between neighborhoods and mental health.

BACKGROUND: The relationship between neighborhood characteristics and resident mental health has been widely investigated in individual studies in recent years, but this literature is not adequately reviewed. AIMS OF THE STUDY: To systematically review relevant individual research of the relation between neighborhoods and adult mental health by identifying and synthesizing all relevant studies in this literature. METHODS: We conducted an electronic search with PubMed and PsycINFO, and manual reference-checking, resulting in 8,562 screened studies of which 29 were selected. Studies were included in the main synthesis if they (i) were published in English in peer reviewed journals; (ii) had relevant definitions and measures of neighborhood characteristics; (iii) utilized standardized measures of adult mental health; (iv) controlled for individual characteristics; (v) reported quantitative results; and, (vi) studied a population in a developed country. We focused on two key areas within this literature: the methodologies utilized to study neighborhood effects and quantitative results. With regard to the former, we examined five major issues: (i) definitions and measures of neighborhoods; (ii) definitions and measures of mental health; (iii) controls for individual level characteristics; (iv) conceptual models; and (v) analytical models. As for quantitative results, the relation was reviewed by types of neighborhood characteristics. We summarized general quantitative findings and drew common conclusions across groups of studies. RESULTS: 27/29 studies found statistically significant association between mental health and at least one measure of neighborhood characteristics, after adjusting for individual factors. This association was evident for all types of neighborhood features, varying from sociodemographic characteristics to physical environment, and from objective to subjective measures. Neighborhood effects were weakened when adding individual-level characteristics into the regression models, and were generally modest relative to individual effects. DISCUSSION AND LIMITATIONS: Although the evidence is highly consistent across studies, detailed evaluation of each individual study reveals a complex reality. The included studies used various study designs and measures of mental health and neighborhoods, making generalization of their relationships less meaningful. It is not possible to conclude that studies with weaker controls for individual characteristics found stronger association between neighborhoods and mental health and vice versa. As only two studies used randomized and controlled trials, causal effects must be interpreted with caution. Formal meta-analysis techniques cannot be used due to large heterogeneity across the included studies. Efficient methods for quantitative analysis remain a great challenge. IMPLICATIONS FOR HEALTH POLICY: The current evidence suggests that efforts to improve mental health may be limited if only individual-level interventions are implemented. The calculation of the costs and benefits of neighborhood-level interventions deserves more attention. Moreover, policy makers may want to incorporate mental health as a measure for evaluating neighborhood improvement programs. IMPLICATIONS FOR FUTURE RESEARCH: There are not enough replicated or comparable studies in this literature to make more precise quantitative conclusions of this relation. Key aspects of study design and analyses could be improved to better understand the true nature of causal relationships. The data resolution of neighborhood characteristics needs to better match with the scale of neighborhood definition that is hypothesized to affect the residents' mental health. As experimental designs are rare in this area, thoughtful use of panel data, instrumental variable (IV) techniques, and other non-experimental approaches deserves further exploration.

Adult↗

Vasorelaxing effect of U50,488H in pulmonary artery and underlying mechanism in rats.

AIM: To investigate the relaxation effect and underlying mechanism of U50,488H (a selective kappa-opioid receptor agonist) in pulmonary artery in the rat. METHODS: Isolated pulmonary artery ring was perfused and the tension of the vessel was measured. RESULTS: U50,488H relaxed the pulmonary artery ring in a dose-dependent manner and the effect was abolished by nor-binaltorphimine, a selective kappa-opioid receptor antagonist. The relaxation effect of U50,488H in pulmonary artery was partially endothelium-dependent and was significantly attenuated in the presence of L-NAME. The relaxation effect of U50,488H was significantly attenuated by K(V) channel blocker 4-AP (4-aminopyridine), but not by glibenclamide (ATP-sensitive K+ channel blocker) nor TEA (tetraethylamonium, Ca2+-activated K+ channel blocker). Further study also showed that endothelium denudation and 4-AP have an additive inhibitory effect on pulmonary artery relaxation caused by U50,488H. CONCLUSION: Kappa-opioid receptor activation by U50,488H relaxes pulmonary artery via two separate pathways: one is endothelium-derived nitric oxide, the other is K(V) channel in pulmonary artery smooth muscle.

3,4-Dichloro-N-methyl-N-(2-(1-pyrrolidinyl)-cycloh↗

ICSI and the transmission of X-autosomal translocation: a three-generation evaluation of X;20 translocation: case report.

Published reports show that male carriers of an X-autosome translocation, which is either inherited from their mother or is de novo, are generally sterile, regardless of the position of the breakpoint in the X chromosome. We report a three-generation propagation of such a translocation in a family with a case of male factor infertility. Due to the condition of severe oligozoospermia, the proband and his wife underwent ICSI, which resulted in the birth of a normal healthy female. Cytogenetic (chromosome) analyses and X-chromosome inactivation (XCI) assays were done on the family. The cytogenetic analysis of the proband, a man with severe oligozoospermia, revealed an X-autosomal translocation, 46,Y,t(X;20)(q10;q10), which was inherited from his mother. His brother had the same translocation. Amniocentesis and post-natal umbilical cord analyses revealed that the female infant carried the same translocation as her father. XCI studies showed highly skewed inactivation of the normal X chromosome in the female infant, her paternal grandmother, and her mother who had a normal karyotype. In contrast to the data from the literature, our study suggests that men with a certain type of X-autosomal translocation could conceive children through ICSI in conditions in which a few spermatogonia are able to complete meiosis II. The literature involving X-autosomal translocation in males is also reviewed and the importance of the study of X-chromosomal inactivation in female infants discussed.

Adult↗

Using foresight methods to anticipate future threats: the case of disease management.

We describe a unique foresight framework for health care managers to use in longer-term planning. This framework uses scenario-building to envision plausible alternate futures of the U.S. health care system and links those broad futures to business-model-specific "load-bearing" assumptions. Because the framework we describe simultaneously addresses very broad and very specific issues, it can be easily applied to a broad range of health care issues by using the broad framework and business-specific assumptions for the particular case at hand. We illustrate this method using the case of disease management, pointing out that although the industry continues to grow rapidly, its future also contains great uncertainties.

Delivery of Health Care↗