Publications by authors named "Shi Ming Luo"

FAM210B (family with sequence similarity 210 member B) is a novel protein that has been linked to tumor development. However, its role and underlying mechanisms in lung adenocarcinoma (LUAD) progression remain largely unexplored. In this study, FAM210B was observed to be down-regulated in LUAD cells.

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Maternal inheritance of mitochondrial DNA (mtDNA) is a widespread phenomenon in eukaryotes. Our earlier research indicated that sperm mtDNA is removed prior to fertilization in mice, and Endonuclease G (ENDOG) orchestrates the degradation of sperm mitochondria in Caenorhabditis elegans. However, the mechanisms underlying sperm mtDNA disposal in mammals remain poorly understood.

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Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) shows promising therapeutic potential in cancer treatment as it is able to trigger extrinsic apoptotic pathways by binding to the cognate death receptor, causing broad-spectrum apoptosis in cancer cells with negligible toxicity to normal cells. However, the majority of cancers display resistance to TRAIL, limiting its clinical utility. Overcoming resistance to TRAIL therapies remains a challenge in the development of effective anti-cancer strategies.

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Article Synopsis
  • The study investigates the role of Formin-like 2 (FMNL2) in mammalian oocyte meiosis, particularly its impact on spindle migration and polar body extrusion.
  • FMNL2 is primarily located at the oocyte cortex and spindle edges; its depletion leads to defects in polar body extrusion and spindle migration due to reduced actin polymerization.
  • Additionally, FMNL2's absence affects mitochondrial and endoplasmic reticulum functions, causing mitochondrial dysfunction and ER stress, but these defects can be rescued by microinjecting FMNL2 mRNA into the affected oocytes.
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Background: Undernourishment in utero has deleterious effects on the metabolism of offspring, but the mechanism of the transgenerational transmission of metabolic disorders is not well known. In the present study, we found that undernourishment in utero resulted in metabolic disorders of female F1 and F2 in mouse model.

Results: Undernutrition in utero induced metabolic disorders of F1 females, which was transmitted to F2 females.

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With the rapid change of people's lifestyle, more childbearing couples live with irregular schedules (i.e., staying up late) and suffer from decreased fertility and abortion, which can be caused by luteal phase defect (LPD).

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Uncontrolled pathogenic genome mutations in germline cells might impair adult fertility, lead to birth defects or even affect the adaptability of a species. Understanding the sources of DNA damage, as well as the features of damage response in germline cells are the overarching tasks to reduce the mutations in germline cells. With the accumulation of human genome data and genetic reports, genome variants formed in germline cells are being extensively explored.

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Mitophagy is a process that selectively degrades mitochondria in cells, and it involves a series of signaling events. Our recent paper shows that the ectopic expression of SQSTM1 and its MAP1LC3B-binding domain (Binding) at the mitochondrial outer membrane, can directly cause mitophagy. To distinguish this mitophagy from others, we called it forced mitophagy.

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Mitochondrial replacement therapy (MRT) has been used to prevent maternal transmission of disease-causing mutations in mitochondrial DNA (mtDNA). However, because MRT requires nuclear transfer, it carries the risk of mtDNA carryover and hence of the reversion of mtDNA to pathogenic levels owing to selective replication and genetic drift. Here we show in HeLa cells, mouse embryos and human embryos that mtDNA heteroplasmy can be reduced by pre-labelling the mitochondrial outer membrane of a donor zygote via microinjection with an mRNA coding for a transmembrane peptide fused to an autophagy receptor, to induce the degradation of the labelled mitochondria via forced mitophagy.

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Cell division consists of nuclear division (mitosis for somatic cells and meiosis for germ cells) and cytoplasmic division (cytokinesis). Embryonic developments are highly programmed, and thus, each cellular event during early embryo development is stable. For mouse embryos, the first time of mitosis is completed about 22 h after fertilization.

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Utilizing microinjection to introduce biological molecules such as DNA, mRNA, siRNA, and proteins into the cell is well established to study oocyte maturation and early embryo development . However, microinjection is an empirical technology. The cellular survival after microinjection is mainly dependent on the operator, and an experienced operator should be trained for a long time, from several months to years.

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Within the development of ovarian follicle, in addition to cell proliferation and differentiation, sophisticated cell-cell cross talks are established among follicular somatic cells such as granulosa cells (GCs) and theca cells. To systematically reveal the cell differentiation and signal transductions in follicular somatic cells, we collected the mouse follicular somatic cells from secondary to ovulatory stage, and analyzed the single cell transcriptomes. Having data filtered and screened, we found 6883 high variable genes in 4888 single cells.

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Article Synopsis
  • Melatonin is crucial for regulating sleep and circadian rhythms, with recent research using single-cell RNA sequencing to explore its gene regulatory networks in the rat pineal gland.
  • The study reveals that autophagy exhibits day/night activation, suggesting it may play a key role in melatonin synthesis and linking the biological clock with the hormone's production.
  • Additionally, ultrastructural analysis shows notable differences in the intracellular structure of pinealocytes between day and night, alongside a preliminary understanding of cell-cell communication in the pineal gland.
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Break-induced replication (BIR) is essential for the repair of DNA double-strand breaks (DSBs) with single ends. DSBs-induced microhomology-mediated BIR (mmBIR) and template-switching can increase the risk of complex genome rearrangement. In addition, DSBs can also induce the multi-invasion-mediated DSB amplification.

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Paraquat (PQ) is a widely used non-selective and oxidizing herbicide in farmland, orchards, flower nursery, and grassland. Overuse of PQ will accumulate in the body and affect the reproduction in mammals. In this study, we found that PQ could reduce the female fertility by oral administration for 21 days in mice.

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Obesity causes many reproductive dysfunctions such as reduced conception, infertility, and early pregnancy loss, and this is largely due to the negative effects of obesity on oocyte and embryo quality. In the present study, we employed single-cell RNA transcriptome sequencing to investigate the potential causes for the maternal obesity effects on mouse embryos. Our results showed that the 4-cell and morula/blastocyst rates were all significantly decreased during embryo development in obese mice.

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Article Synopsis
  • - Mitochondrial energy insufficiency is linked to issues with oocyte activation, and calcium (Ca) plays a key role in supporting mitochondrial energy, though the mechanisms are not well understood.
  • - Researchers used a specific Ca probe (Mt-GCaMP6s) to study changes in mitochondrial calcium during oocyte maturation and activation, discovering that mitochondria near the nucleus had higher calcium levels compared to those at the cell's edges.
  • - The study suggests that elevated calcium levels in mitochondria near chromosomes help energize the oocyte for spindle formation, and that synchronized calcium dynamics between mitochondria and the cytoplasm are critical for successful oocyte activation.
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During oocyte meiosis, mitochondria usually surround spindle to meet the energy demand of spindle migration and chromosome segregation. Therefore, the mitochondrion surrounding spindle is widely accepted as an important indicator to demonstrate the mitochondrial function in oocyte studies. However, the role of mitochondria surrounding spindle in oocyte quality is not exactly addressed.

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Meiotic maturation of oocyte is an important process for successful fertilization, in which cytoskeletal integrality takes a significant role. The p-21 activated kinases (PAKs) belong to serine/threonine kinases that affect wide range of processes that are crucial for cell motility, survival, cell cycle, and proliferation. In this study, we used a highly selective inhibitor of PAK4, PF-3758309, to investigate the functions of PAK4 during meiotic maturation of mouse oocytes.

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Germ cell-derived genomic structure variants not only drive the evolution of species but also induce developmental defects in offspring. The genomic structure variants have different types, but most of them are originated from DNA double-strand breaks (DSBs). It is still not well known whether DNA DSBs exist in adult mammalian oocytes and how the growing and fully grown oocytes repair their DNA DSBs induced by endogenous or exogenous factors.

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  • Repeated superovulation negatively impacts mouse ovaries and cumulus cells, but its effects on early embryos were previously unclear.
  • The study found that as the number of superovulations increased, fertilization rates and early embryo development decreased, with changes in gene expression related to stem cell maintenance.
  • Additionally, histone modifications in embryos were altered; acetylation levels of key histones decreased while methylation levels increased, suggesting that superovulation disrupts epigenetic reprogramming in early development.
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Organophosphorus insecticide diazinon (DZN) is diffusely used in agriculture, home gardening, and crop peats. Much work so far has focused on the link between DZN exposure and the occurrence of neurological diseases, while little is known on the reproductive toxicological assessment on DZN exposure. This research aimed to investigate the underlying mechanisms of toxic hazards for DZN exposure on cultured porcine ovarian granulosa cells.

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Background: The human oocyte transmits one set of haploid genome into female pronucleus (FPN) while discards the remaining genome into the first polar body (PB1) and the second polar body (PB2). The FPN genome carries an assembly of maternal and paternal genome that resulted from homologous recombination during the prophase of the first meiosis. However, how parental genome has been shuffled and transmitted is difficult to assess by analysing only the progeny's genome.

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Malathion is a wide spectrum organophosphorothionate insecticide that is frequently found in drinking water, food and foodstuffs. Ovarian granulosa cells modulate oogenesis by providing metabolic nutrients to oocytes. They can decide the fate of folliculogenesis and oocyte maturation by supplying regulatory cues that help in reproduction.

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Benzo[ghi]perylene (B[ghi]P) is a polycyclic aromatic hydrocarbon widely found in haze. Long-term exposure to humans or animals can cause serious damage to the respiratory system. Melatonin is an endogenous natural hormone synthesized and released by the pineal gland.

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