Lingfeng Luo

All Publications

• Cardiovascular Disease and Breast Cancer Stage at Diagnosis. JAMA network open Angelov, I., Haas, A. M., Brock, E., Luo, L., Zhao, J., Smith, B. D., Giordano, S. H., Leeper, N. J., Nead, K. T. 2025; 8 (1): e2452890

  Abstract

  Cardiovascular disease (CVD) and cancer are the leading causes of mortality in the US. Large-scale population-based and mechanistic studies support a direct effect of CVD on accelerated tumor growth and spread, specifically in breast cancer.To assess whether individuals presenting with advanced breast cancers are more likely to have prevalent CVD compared with those with early-stage breast cancers at the time of diagnosis.This population-based case-control study used data from the Surveillance, Epidemiology, and End Results-Medicare linked databases from 2009 to 2020. The analysis was completed from May 2023 to August 2024. Participants were female patients aged at least 66 years diagnosed with invasive breast cancer. Cases were matched with controls by breast cancer stage at diagnosis and propensity scores using factors known to be associated with delayed cancer diagnosis.Prevalent CVD prior to breast cancer diagnosis.The outcome of interest was the odds of locally advanced (T3-4 or N+) or metastatic (M+) breast cancer status at diagnosis.The full analytic cohort included 19 292 matched individuals, with median (IQR) age 73 (70-79) years, of whom 1676 (8.7%) were Black and 16 681 (86.5%) were White; 9478 individuals (49.1%) had prevalent CVD. Propensity score-matched, multivariable-adjusted models found that individuals with locally advanced or metastatic breast cancer at diagnosis had statistically significantly increased odds of prevalent CVD (odds ratio [OR], 1.10; 95% CI, 1.03-1.17; P = .007). This association was observed among hormone receptor-positive (OR, 1.11; 95% CI, 1.03-1.19; P = .006) but not hormone receptor-negative (OR, 1.02; 95% CI, 0.86-1.21; P = .83) breast cancer. ORs were directionally consistent when separately examining locally advanced (OR, 1.09; 95% CI, 1.02-1.17; P = .02) and metastatic (OR, 1.20; 95% CI, 0.94-1.54; P = .15) disease, among all receptor subtypes.This case-control study found that individuals with more advanced breast cancer at diagnosis were more likely to have prevalent CVD. This finding may be specific to hormone receptor-positive and ERBB2-negative (formerly HER2) disease. Future studies are needed to confirm these findings and investigate interventions to improve patient outcomes, including personalized cancer screening.

  View details for DOI 10.1001/jamanetworkopen.2024.52890

  View details for PubMedID 39745699

  View details for PubMedCentralID PMC11696447

• Protocol for tyramide signal amplification immunohistochemical detection of Notch1 signaling in the vascular system. STAR protocols Lin, Y., Singh, S., Xu, C., Wang, Z., Feng, C., Jiang, D., Luo, L., Li, W., Che, W., Zhu, G. 2024; 5 (4): 103519

  Abstract

  Notch signaling is a pivotal regulator in the vascular system that is essential for development, angiogenesis, and maintaining vascular homeostasis. Here, we present a protocol for tyramide signal amplification (TSA) immunohistochemistry, tailored explicitly for detecting Notch signaling components in vascular tissues. We describe steps for utilizing tailored antigen retrieval techniques, specific blocking solutions, and a complex of avidin/biotin-horseradish peroxidase conjugate with tyramide, along with optimized washing steps. For complete details on the use and execution of this protocol, please refer to Zhu et al.1.

  View details for DOI 10.1016/j.xpro.2024.103519

  View details for PubMedID 39661510

• Vascular smooth muscle cell plasticity in the tumor microenvironment. Cancer communications (London, England) Bell, C. F., Baylis, R. A., Lopez, N. G., Ma, W. F., Gao, H., Wang, F., Bamezai, S., Fu, C., Kojima, Y., Adkar, S. S., Luo, L., Miller, C. L., Leeper, N. J. 2024

  View details for DOI 10.1002/cac2.12635

  View details for PubMedID 39648671

• Pro-efferocytic nanotherapies reduce vascular inflammation without inducing anemia in a large animal model of atherosclerosis. Nature communications Bamezai, S., Zhang, Y., Kumari, M., Lotfi, M., Alsaigh, T., Luo, L., Kumar, G. S., Wang, F., Ye, J., Puri, M., Manchanda, R., Paluri, S., Adkar, S. S., Kojima, Y., Ingelsson, A., Bell, C. F., Lopez, N. G., Fu, C., Choi, R. B., Miller, Z., Barrios, L., Walsh, S., Ahmad, F., Maegdefessel, L., Smith, B. R., Leeper, N. J. 2024; 15 (1): 8034

  Abstract

  Atherosclerosis is an inflammatory disorder responsible for cardiovascular disease. Reactivation of efferocytosis, the phagocytic removal of cells by macrophages, has emerged as a translational target for atherosclerosis. Systemic blockade of the key 'don't-eat-me' molecule, CD47, triggers the engulfment of apoptotic vascular tissue and potently reduces plaque burden. However, it also induces red blood cell clearance, leading to anemia. To overcome this, we previously developed a macrophage-specific nanotherapy loaded with a chemical inhibitor that promotes efferocytosis. Because it was found to be safe and effective in murine studies, we aimed to advance our nanoparticle into a porcine model of atherosclerosis. Here, we demonstrate that production can be scaled without impairing nanoparticle function. At an early stage of disease, we find our nanotherapy reduces apoptotic cell accumulation and inflammation in the atherosclerotic lesion. Notably, this therapy does not induce anemia, highlighting the translational potential of targeted macrophage checkpoint inhibitors.

  View details for DOI 10.1038/s41467-024-52005-1

  View details for PubMedID 39271657

  View details for PubMedCentralID 4826466

• Cancer Incidence After Diagnosis of Abdominal Aortic Aneurysm. Arteriosclerosis, thrombosis, and vascular biology Luo, L., Haas, A. M., Bell, C. F., Baylis, R. A., Adkar, S. S., Fu, C., Angelov, I., Giordano, S. H., Klarin, D., Leeper, N. J., Nead, K. T. 2024

  Abstract

  Epidemiological and mechanistic data support a potential causal link between cardiovascular disease (CVD) and cancer. Abdominal aortic aneurysms (AAAs) represent a common form of CVD with at least partially distinct genetic and biologic etiology from other forms of CVD. The risk of cancer and how this risk differs compared with other forms of CVD, is unknown among AAA patients. We conducted a retrospective cohort study using the IBM MarketScan Research Database to test whether individuals with AAA have a higher cancer risk independent of traditional shared risk factors.All individuals ≥18 years of age with ≥36 months of continuous coverage between 2008 and 2020 were enrolled. Those with potential Mendelian etiologies of AAA, aortic aneurysm with nonspecific anatomic location, or a cancer diagnosis before the start of follow-up were excluded. A subgroup analysis was performed of individuals having the Health Risk Assessment records including tobacco use and body mass index. The following groups of individuals were compared: (1) with AAA, (2) with non-AAA CVD, and (3) without any CVD.The propensity score-matched cohort included 58 993 individuals with AAA, 117 986 with non-AAA CVD, and 58 993 without CVD. The 5-year cumulative incidence of cancer was 13.1% (12.8%-13.5%) in participants with AAA, 10.1% (9.9%-10.3%) in participants with non-AAA CVD, and 9.6% (9.3%-9.9%) in participants without CVD. Multivariable-adjusted Cox proportional hazards regression models found that patients with AAA exhibited a higher cancer risk than either those with non-AAA CVD (hazard ratio, 1.28 [95% CI, 1.23-1.32]; P<0.001) or those without CVD (hazard ratio, 1.32 [95% CI, 1.26-1.38]; P<0.001). Results remained consistent after excluding common smoking-related cancers and when adjusting for tobacco use and body mass index.Patients with AAA may have a unique risk of cancer requiring further mechanistic study and investigation of the role of enhanced cancer screening.

  View details for DOI 10.1161/ATVBAHA.123.320543

  View details for PubMedID 38779853

• Role of vascular smooth muscle cell clonality in atherosclerosis. Frontiers in cardiovascular medicine Luo, L., Fu, C., Bell, C. F., Wang, Y., Leeper, N. J. 2023; 10: 1273596

  Abstract

  Atherosclerotic cardiovascular disease remains the leading cause of death worldwide. While many cell types contribute to the growing atherosclerotic plaque, the vascular smooth muscle cell (SMC) is a major contributor due in part to its remarkable plasticity and ability to undergo phenotype switching in response to injury. SMCs can migrate into the fibrous cap, presumably stabilizing the plaque, or accumulate within the lesional core, possibly accelerating vascular inflammation. How SMCs expand and react to disease stimuli has been a controversial topic for many decades. While early studies relying on X-chromosome inactivation were inconclusive due to low resolution and sensitivity, recent advances in multi-color lineage tracing models have revitalized the concept that SMCs likely expand in an oligoclonal fashion during atherogenesis. Current efforts are focused on determining whether all SMCs have equal capacity for clonal expansion or if a "stem-like" progenitor cell may exist, and to understand how constituents of the clone decide which phenotype they will ultimately adopt as the disease progresses. Mechanistic studies are also beginning to dissect the processes which confer cells with their overall survival advantage, test whether these properties are attributable to intrinsic features of the expanding clone, and define the role of cross-talk between proliferating SMCs and other plaque constituents such as neighboring macrophages. In this review, we aim to summarize the historical perspectives on SMC clonality, highlight unanswered questions, and identify translational issues which may need to be considered as therapeutics directed against SMC clonality are developed as a novel approach to targeting atherosclerosis.

  View details for DOI 10.3389/fcvm.2023.1273596

  View details for PubMedID 38089777

  View details for PubMedCentralID PMC10713728

• Role of cAMP in Cardiomyocyte Viability: Beneficial or Detrimental? Circulation research Zhang, Y., Chen, S., Luo, L., Greenly, S., Shi, H., Jiayuan Xu, J., Yan, C. 2023

  Abstract

  3', 5'-cyclic AMP (cAMP) regulates numerous cardiac functions. Various hormones and neurotransmitters elevate intracellular cAMP (i[cAMP]) in cardiomyocytes through activating stimulatory GsPCRs (G protein [Gs]-coupled receptors) and membrane-bound ACs (adenylyl cyclases). Increasing evidence has indicated that stimulating different GsPCRs and ACs exhibits distinct, even opposite effects, on cardiomyocyte viability. However, the underlying mechanisms are not fully understood.We used molecular and pharmacological approaches to investigate how different GsPCR/cAMP signaling differentially regulate cardiomyocyte viability with in vitro, ex vivo, and in vivo models.For prodeath GsPCRs, we explored beta1-adrenergic-receptor and histamine-H2-receptor. We found that their prodeath effects were similarly dependent on AC5 activation, ATP release to the extracellular space via PANX1 (pannexin-1) channel, and extracellular ATP (e[ATP])-mediated signaling involving in P2X7R (P2X purinoceptor 7) and CaMKII (Ca2+/calmodulin-dependent protein kinase II). PANX1 phosphorylation at Serine 206 by cAMP-dependent-PKA (protein-kinase-A) promoted PANX1 activation, which was critical in beta1-adrenergic-receptor- or histamine-H2-receptor-induced cardiomyocyte death in vitro and in vivo. Beta1-adrenergic-receptor or histamine-H2-receptor was localized proximately to PANX1, which permits ATP release. For prosurvival GsPCRs, we explored adenosine-A2-receptor (A2R), calcitonin-gene-related-peptide-receptor, and RXFP1 (relaxin-family peptide-receptor 1). Their prosurvival effects were dependent on AC6 activation, cAMP efflux via MRP4 (multidrug resistance protein 4), extracellular cAMP metabolism to adenosine (e[cAMP]-to-e[ADO]), and e[ADO]-mediated signaling. A2R, calcitonin-gene-related-peptide-receptor, or RXFP1 was localized proximately to MRP4, which enables cAMP efflux. Interestingly, exogenously increasing e[cAMP] levels by membrane-impermeable cAMP protected against cardiomyocyte death in vitro and in ex vivo and in vivo mouse hearts with ischemia-reperfusion injuries.Our findings indicate that the functional diversity of different GsPCRs in cardiomyocyte viability could be achieved by their ability to form unique signaling complexes (signalosomes) that determine the fate of cAMP: either stimulate ATP release by activating PKA or directly efflux to be e[cAMP].

  View details for DOI 10.1161/CIRCRESAHA.123.322652

  View details for PubMedID 37850368

• Identifying shared transcriptional risk patterns between atherosclerosis and cancer. iScience Baylis, R. A., Gao, H., Wang, F., Bell, C. F., Luo, L., Björkegren, J. L., Leeper, N. J. 2023; 26 (9): 107513

  Abstract

  Cancer and cardiovascular disease (CVD) are the leading causes of death worldwide. Numerous overlapping pathophysiologic mechanisms have been hypothesized to drive the development of both diseases. Further investigation of these common pathways could allow for the identification of mutually detrimental processes and therapeutic targeting to derive mutual benefit. In this study, we intersect transcriptomic datasets correlated with disease severity or patient outcomes for both cancer and atherosclerotic CVD. These analyses confirmed numerous pathways known to underlie both diseases, such as inflammation and hypoxia, but also identified several novel shared pathways. We used these to explore common translational targets by applying the drug prediction software, OCTAD, to identify compounds that simultaneously reverse the gene expression signature for both diseases. These analyses suggest that certain tumor-specific therapeutic approaches may be implemented so that they avoid cardiovascular consequences, and in some cases may even be used to simultaneously target co-prevalent cancer and atherosclerosis.

  View details for DOI 10.1016/j.isci.2023.107513

  View details for PubMedID 37636064

  View details for PubMedCentralID PMC10448075

• Spatial Metabolomics and the Vulnerable Atherosclerotic Plaque. Arteriosclerosis, thrombosis, and vascular biology Luo, L., Leeper, N. J. 2023

  View details for DOI 10.1161/ATVBAHA.123.319739

  View details for PubMedID 37534466

• Risk of Cancer After Diagnosis of Cardiovascular Disease. JACC. CardioOncology Bell, C. F., Lei, X., Haas, A., Baylis, R. A., Gao, H., Luo, L., Giordano, S. H., Wehner, M. R., Nead, K. T., Leeper, N. J. 2023; 5 (4): 431-440

  Abstract

  Cardiovascular disease (CVD) and cancer share several risk factors. Although preclinical models show that various types of CVD can accelerate cancer progression, clinical studies have not determined the impact of atherosclerosis on cancer risk.The objective of this study was to determine whether CVD, especially atherosclerotic CVD, is independently associated with incident cancer.Using IBM MarketScan claims data from over 130 million individuals, 27 million cancer-free subjects with a minimum of 36 months of follow-up data were identified. Individuals were stratified by presence or absence of CVD, time-varying analysis with multivariable adjustment for cardiovascular risk factors was performed, and cumulative risk of cancer was calculated. Additional analyses were performed according to CVD type (atherosclerotic vs nonatherosclerotic) and cancer subtype.Among 27,195,088 individuals, those with CVD were 13% more likely to develop cancer than those without CVD (HR: 1.13; 95% CI: 1.12-1.13). Results were more pronounced for individuals with atherosclerotic CVD (aCVD), who had a higher risk of cancer than those without CVD (HR: 1.20; 95% CI: 1.19-1.21). aCVD also conferred a higher risk of cancer compared with those with nonatherosclerotic CVD (HR: 1.11; 95% CI: 1.11-1.12). Cancer subtype analyses showed specific associations of aCVD with several malignancies, including lung, bladder, liver, colon, and other hematologic cancers.Individuals with CVD have an increased risk of developing cancer compared with those without CVD. This association may be driven in part by the relationship of atherosclerosis with specific cancer subtypes, which persists after controlling for conventional risk factors.

  View details for DOI 10.1016/j.jaccao.2023.01.010

  View details for PubMedID 37614573

  View details for PubMedCentralID PMC10443115

• Clustering cancers by shared transcriptional risk reveals novel targets for cancer therapy. Molecular cancer Gao, H., Baylis, R. A., Luo, L., Kojima, Y., Bell, C. F., Ross, E. G., Wang, F., Leeper, N. J. 2022; 21 (1): 116

  View details for DOI 10.1186/s12943-022-01592-y

  View details for PubMedID 35585548

• The pleiotropic benefits of statins include the ability to reduce CD47 and amplify the effect of pro-efferocytic therapies in atherosclerosis. Nature cardiovascular research Jarr, K., Ye, J., Kojima, Y., Ye, Z., Gao, H., Schmid, S., Luo, L., Baylis, R. A., Lotfi, M., Lopez, N., Eberhard, A. V., Smith, B. R., Weissman, I. L., Maegdefessel, L., Leeper, N. J. 2022; 1 (3): 253-262

  Abstract

  The pleiotropic benefits of statins may result from their impact on vascular inflammation. The molecular process underlying this phenomenon is not fully elucidated. Here, RNA sequencing designed to investigate gene expression patterns following CD47-SIRPalpha inhibition identifies a link between statins, efferocytosis, and vascular inflammation. In vivo and in vitro studies provide evidence that statins augment programmed cell removal by inhibiting the nuclear translocation of NFkappaB1 p50 and suppressing the expression of the critical 'don't eat me' molecule, CD47. Statins amplify the phagocytic capacity of macrophages, and thus the anti-atherosclerotic effects of CD47-SIRPalpha blockade, in an additive manner. Analyses of clinical biobank specimens suggest a similar link between statins and CD47 expression in humans, highlighting the potential translational implications. Taken together, our findings identify efferocytosis and CD47 as pivotal mediators of statin pleiotropy. In turn, statins amplify the anti-atherosclerotic effects of pro-phagocytic therapies independently of any lipid-lowering effect.

  View details for DOI 10.1038/s44161-022-00023-x

  View details for PubMedID 35990913

• Dynamic changes in chromatin accessibility are associated with the atherogenic transitioning of vascular smooth muscle cells. Cardiovascular research Wang, Y., Gao, H., Wang, F., Ye, Z., Mokry, M., Turner, A. W., Ye, J., Koplev, S., Luo, L., Alsaigh, T., Adkar, S. S., Elishaev, M., Gao, X., Maegdefessel, L., Bjorkegren, J. L., Pasterkamp, G., Miller, C. L., Ross, E. G., Leeper, N. J. 2021

  Abstract

  AIMS: De-differentiation and activation of pro-inflammatory pathways are key transitions vascular smooth muscle cells (SMCs) make during atherogenesis. Here, we explored the upstream regulators of this 'atherogenic transition'.METHODS AND RESULTS: Genome-wide sequencing studies, including ATAC-seq (Assay for Transposase-Accessible Chromatin using sequencing) and RNA-seq, were performed on cells isolated from both murine SMC-lineage tracing models of atherosclerosis and human atherosclerotic lesions. At the bulk level, alterations in chromatin accessibility were associated with the atherogenic transitioning of lesional SMCs, especially in relation to genes that govern differentiation status and complement-dependent inflammation. Using computational biology, we observed that a transcription factor previously related to coronary artery disease, ATF3 (Activating transcription factor 3), was predicted to be an upstream regulator of genes altered during the transition. At the single-cell level, our results indicated that ATF3 is a key repressor of SMC transitioning towards the subset of cells that promote vascular inflammation by activating the complement cascade. The expression of ATF3 and complement component C3 were negatively correlated in SMCs from human atherosclerotic lesions, suggesting translational relevance. Phenome-wide association studies indicated that genetic variation that results in reduced expression of ATF3 is correlated with an increased risk for atherosclerosis, and the expression of ATF3 was significantly downregulated in humans with advanced vascular disease.CONCLUSION: Our study indicates that the plasticity of atherosclerotic SMCs may in part be explained by dynamic changes in their chromatin architecture, which in turn may contribute to their maladaptive response to inflammation-induced stress.TRANSLATIONAL PERSPECTIVE: The recent CANTOS and COLCOT trials have shown that targeting inflammatory pathways lowers the risk of major adverse cardiovascular events. However, more specific targets are needed to avoid immunosuppressive side effects. Our data identify an upstream regulator of pro-inflammatory SMCs, ATF3, which is involved in the initial atherogenic transitioning of lesional SMCs. Restoring ATF3 activity may prevent the de-differentiation of SMCs and offer a novel translational approach for the suppression of complement-dependent inflammation in atherosclerotic lesions.

  View details for DOI 10.1093/cvr/cvab347

  View details for PubMedID 34849613

• Efficient suppression of vascular smooth muscle cell proliferation and intimal hyperplasia by targeting phosphodiesterase 10A Luo, L., Zhang, Y., Hsu, C., Korshunov, V., Long, X., Knight, P., Berk, B., Yan, C. SAGE PUBLICATIONS LTD. 2021: NP4-NP5

  View details for Web of Science ID 000704017100022

• Role of PDE10A in vascular smooth muscle cell hyperplasia and pathological vascular remodeling Cardiovascular Research Luo, L., Cai, Y., Zhang, Y., Hsu, C. G., Korshunov, V. A., Long, X., Knight, P. A., Berk, B. C., Yan, C. 2021

  View details for DOI 10.1093/cvr/cvab304

• The Protective Role of Natriuretic Peptide Receptor 2 against High Salt Injury in the Renal Papilla. The American journal of pathology Dugbartey, G. J., Quinn, B., Luo, L., Mickelsen, D. M., Ture, S. K., Morrell, C. N., Czyzyk, J., Doyley, M. M., Yan, C., Berk, B. C., Korshunov, V. A. 2019; 189 (9): 1721-1731

  Abstract

  Mutations in natriuretic peptide receptor 2 (Npr2) gene cause a rare form of short-limbed dwarfism, but its physiological effects have not been well studied. Human and mouse genetic data suggest that Npr2 in the kidney plays a role in salt homeostasis. Herein, we described anatomic changes within renal papilla of Npr2 knockout (Npr2-/-) mice. Dramatic reduction was found in diuresis, and albuminuria was evident after administration of 1% NaCl in drinking water in Npr2-/- and heterozygous (Npr2+/-) mice compared with their wild-type (Npr2+/+) littermates. There was indication of renal epithelial damage accompanied by high numbers of red blood cells and inflammatory cells (macrophage surface glycoproteins binding to galectin-3) and an increase of renal epithelial damage marker (T-cell Ig and mucin domain 1) in Npr2-/- mice. Addition of 1% NaCl tended to increase apoptotic cells (cleaved caspase 3) in the renal papilla of Npr2-/- mice. In vitro, genetic silencing of the Npr2 abolished protective effects of C-type natriuretic peptide, a ligand for Npr2, against death of M-1 kidney epithelial cells exposed to 360 mmol/L NaCl. Finally, significantly lower levels of expression of the NPR2 protein were detected in renal samples of hypertensive compared with normotensive human subjects. Taken together, these findings suggest that Npr2 is essential to protect renal epithelial cells from high concentrations of salt and prevent kidney injury.

  View details for DOI 10.1016/j.ajpath.2019.05.020

  View details for PubMedID 31220449

  View details for PubMedCentralID PMC6724224

• SIRT6 Is Responsible for More Efficient DNA Double-Strand Break Repair in Long-Lived Species. Cell Tian, X., Firsanov, D., Zhang, Z., Cheng, Y., Luo, L., Tombline, G., Tan, R., Simon, M., Henderson, S., Steffan, J., Goldfarb, A., Tam, J., Zheng, K., Cornwell, A., Johnson, A., Yang, J. N., Mao, Z., Manta, B., Dang, W., Zhang, Z., Vijg, J., Wolfe, A., Moody, K., Kennedy, B. K., Bohmann, D., Gladyshev, V. N., Seluanov, A., Gorbunova, V. 2019; 177 (3): 622-638.e22

  Abstract

  DNA repair has been hypothesized to be a longevity determinant, but the evidence for it is based largely on accelerated aging phenotypes of DNA repair mutants. Here, using a panel of 18 rodent species with diverse lifespans, we show that more robust DNA double-strand break (DSB) repair, but not nucleotide excision repair (NER), coevolves with longevity. Evolution of NER, unlike DSB, is shaped primarily by sunlight exposure. We further show that the capacity of the SIRT6 protein to promote DSB repair accounts for a major part of the variation in DSB repair efficacy between short- and long-lived species. We dissected the molecular differences between a weak (mouse) and a strong (beaver) SIRT6 protein and identified five amino acid residues that are fully responsible for their differential activities. Our findings demonstrate that DSB repair and SIRT6 have been optimized during the evolution of longevity, which provides new targets for anti-aging interventions.

  View details for DOI 10.1016/j.cell.2019.03.043

  View details for PubMedID 31002797

  View details for PubMedCentralID PMC6499390

• Small non-coding RNAs and their associated proteins in spermatogenesis. Gene Luo, L. F., Hou, C. C., Yang, W. X. 2016; 578 (2): 141-57

  Abstract

  The importance of the gene regulation roles of small non-coding RNAs and their protein partners is of increasing focus. In this paper, we reviewed three main small RNA species which appear to affect spermatogenesis. MicroRNAs (miRNAs) are single stand RNAs derived from transcripts containing stem-loops and hairpins which target corresponding mRNAs and affect their stability or translation. Many miRNA species have been found to be related to normal male germ cell development. The biogenesis of piRNAs is still largely unknown but several models have been proposed. Some piRNAs and PIWIs target transposable elements and it is these that may be active in regulating translation or stem cell maintenance. endo-siRNAs may also participate in sperm development. Some possible interactions between different kinds of small RNAs have even been suggested. We also show that male germ granules are seen to have a close relationship with a considerable number of mRNAs and small RNAs. Those special structures may also participate in sperm development.

  View details for DOI 10.1016/j.gene.2015.12.020

  View details for PubMedID 26692146

• Endometrial stromal cells and decidualized stromal cells: origins, transformation and functions. Gene Zhu, H., Hou, C. C., Luo, L. F., Hu, Y. J., Yang, W. X. 2014; 551 (1): 1-14

  Abstract

  Decidualization of endometrium, which is characterized by endometrial stromal cell (ESC) decidualization, vascular reconstruction, immune cell recruitment, and plentiful molecule production, is a crucial step for uterus to become receptive for embryo. When implantation takes place, ESCs surround and directly interact with embryo. Decidualized stromal cells (DSCs) are of great importance in endometrial decidualization, having a broad function in regulating immune activity and vascular remodeling of uterus. DSCs are shown to have a higher metabolic level and looser cytoskeleton than ESCs. What's the origin of ESCs and how ESCs successfully transform into DSCs had puzzled scientists in the last decades. Breakthrough had been achieved recently, and many studies had elucidated some of the characters and functions of DSCs. However, several questions still remain unclear. This paper reviews current understanding of where ESCs come from and how ESCs differentiate into DSCs, summarizes some characters and functions of DSCs, analyzes current studies and their limitations and points out research areas that need further investigation.

  View details for DOI 10.1016/j.gene.2014.08.047

  View details for PubMedID 25168894

• Nuclear factors: roles related to mitochondrial deafness. Gene Luo, L. F., Hou, C. C., Yang, W. X. 2013; 520 (2): 79-89

  Abstract

  Hearing loss (HL) is a common disorder with mitochondrial dysfunction as one of the major causes leading to deafness. Mitochondrial dysfunction may be caused by either mutations in nuclear genes leading to defective nuclear-encoded proteins or mutations in mitochondrial genes leading to defective mitochondrial-encoded products. The specific nuclear genes involved in HL can be classified into two categories depending on whether mitochondrial gene mutations co-exist (modifier genes) or not (deafness-causing genes). TFB1M, MTO1, GTPBP3, and TRMU are modifier genes. A mutation in any of these modifier genes may lead to a deafness phenotype when accompanied by the mitochondrial gene mutation. OPA1, TIMM8A, SMAC/DIABLO, MPV17, PDSS1, BCS1L, SUCLA2, C10ORF2, COX10, PLOG1and RRM2B are deafness-causing genes. A mutation in any of these deafness-causing genes will directly induce variable phenotypic HL.

  View details for DOI 10.1016/j.gene.2013.03.041

  View details for PubMedID 23510774