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1.
Chemistry ; 29(72): e202303058, 2023 Dec 22.
Article in English | MEDLINE | ID: mdl-37851869

ABSTRACT

Chirality is a fundamental characteristic of nature. Expanded porphyrinoids and their analogues offer an attractive platform for delving into the intricacies of chirality. Expanded porphyrinoids comprise pyrrolic macrocycles and related heterocyclic systems. As a class, expanded porphyrinoids are widely recognized for their flexible structural features, nontrivial coordination capabilities, and intriguing optical and electronic properties. With limited exceptions, their inherent conformational flexibility coupled with a low racemization barrier allows for the facile interchange between enantiomers. As a result, achieving the effective chiral resolution of individual enantiomers and the subsequent exploration of their chiroptical properties represents a significant challenge. This review summarizes strategies used to realize the chiral resolution of expanded porphyrinoids and the understanding of intrinsic chiroptical properties that has emerged from these separation efforts. It is our hope that this review will serve not only to codify our current understanding of chiral expanded porphyrinoids, but also inspire advances in the generalized area of chiral functional materials.

2.
Eur J Immunol ; 53(11): e2350474, 2023 11.
Article in English | MEDLINE | ID: mdl-37489253

ABSTRACT

Kupffer cells (KCs) are liver-resident macrophages involved in hepatic inflammatory responses, including nonalcoholic fatty liver disease (NAFLD) development. However, the contribution of KC subsets to liver inflammation remains unclear. Here, using high-dimensional single-cell RNA sequencing, we characterized murine embryo-derived KCs and identified two KC populations with different gene expression profiles: KC-1 and KC-2. KC-1 expressed CD170, exhibiting immunoreactivity and immune-regulatory abilities, while KC-2 highly expressed lipid metabolism-associated genes. In a high-fat diet-induced NAFLD model, KC-1 cells differentiated into pro-inflammatory phenotypes and initiated more frequent communications with invariant natural killer T (iNKT) cells. In KC-1, interleukin (IL)-10 expression was unaffected by the high-fat diet but impaired by iNKT cell ablation and upregulated by iNKT cell adoptive transfer in vivo. Moreover, in a cellular co-culture system, primary hepatic iNKT cells promoted IL-10 expression in RAW264.7 and primary KC-1 cells. CD206 signal blocking in KC-1 or CD206 knockdown in RAW264.7 cells significantly reduced IL-10 expression. In conclusion, we identified two embryo-derived KC subpopulations with distinct transcriptional profiles. The CD206-mediated crosstalk between iNKT and KC-1 cells maintains IL-10 expression in KC-1 cells, affecting hepatic immune balance. Therefore, KC-based therapeutic strategies must consider cellular heterogeneity and the local immune microenvironment for enhanced specificity and efficiency.


Subject(s)
Natural Killer T-Cells , Non-alcoholic Fatty Liver Disease , Humans , Animals , Mice , Kupffer Cells , Interleukin-10 , Liver , Mice, Inbred C57BL
3.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 39(2): 124-129, 2023 Feb.
Article in Chinese | MEDLINE | ID: mdl-36872430

ABSTRACT

Objective To investigate the therapeutic effect of bone marrow cell adoptive therapy on metabolic-dysfunction-associated fatty liver disease (MAFLD) in mice and its possible cell population. Methods The staining was used to detect the liver lesions of MAFLD in C57BL/6 mice induced by methionine and choline deficiency diet (MCD) and the adoptive therapeutic effect of bone marrow cells on MAFLD was evaluated by detecting the levels of serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST). The mRNA expressions of low density lipoprotein receptor (LDLR) and interleukin-4 (IL-4) in liver immune cells (including T, NKT, Kupffer cells and other cell populations) were detected by real-time quantitative PCR. The bone marrow cells labeled with 5, 6- carboxyfluorescein diacetate succinimidyl ester (CFSE) were injected into the tail vein of mice. The proportion of CFSE positive cells in liver tissue was observed by the frozen section, and the proportion of labeled cells in the liver and spleen was tracked by flow cytometry. The expression of CD3, CD4, CD8, NK1.1, CD11b and Gr-1 in CFSE labeled adoptive cells was detected by flow cytometry. The intracellular lipid content of NKT cells in liver tissue was evaluated by Nile Red lipid staining. Results The injury of liver tissue and the levels of serum ALT and AST in MAFLD mice were significantly reduced. At the same time, liver immune cells up-regulated the expression of IL-4 and LDLR. LDLR knockout mice induced more severe MAFLD after giving MCD diet. Bone marrow adoptive cells had a significant therapeutic effect and differentiated more NKT cells to colonize the liver. At the same time, the intracellular lipids of these NKT cells increased significantly. Conclusion Bone marrow cell adoptive therapy can reduce liver injury in MAFLD mice by differentiating more NKT cells and increasing the intracellular lipid content of these cells.


Subject(s)
Natural Killer T-Cells , Non-alcoholic Fatty Liver Disease , Animals , Mice , Mice, Inbred C57BL , Interleukin-4 , Methionine , Racemethionine , Bone Marrow Cells , Killer Cells, Natural , Lipids
4.
Am J Reprod Immunol ; 89(6): e13633, 2023 06.
Article in English | MEDLINE | ID: mdl-36250899

ABSTRACT

PROBLEM: Endometriosis patients undergoing in vitro fertilization-embryo transfer (IVF-ET) treatment suffer from poor oocyte quality, a reduced likelihood of the fertilization rate, and low embryo quality. The dysregulation of immune cells and cytokine profiles in the follicular fluid (FF) may play an important role in the competence of the oocyte and the development of the embryo, but the mechanism remains largely unknown. METHOD OF STUDY: A total of 40 proved advanced staged endometriosis patients were enrolled in this study. The pregnancy results were followed until all the embryos collected by the first oocyte retrieval cycle were used up. The immune cells subtypes in FF and serum collected on the day of oocyte retrieval were detected by flow cytometry and 27 cytokines were determined using the Bio-Plex Pro Human Cytokine 27-Plex Immunoassay. The specific effect of cytokine on the gene expression of human granulosa cells was determined by RT-qPCR. RESULTS: The fertilization rate and the cumulative live birth rate were significantly lower in the endometriosis group. The ratio of CD4+ /CD8+ T cells in FF was significantly lower, while the level of IP-10, RANTES and G-CSF were statistically higher in the endometriosis group. The level of IP-10 correlated with the IVF outcome. Moreover, treated by IP-10, the mRNA level of FSHR and CYP19A1 the human granulosa cells were downregulated in vitro. CONCLUSION: These results suggest that alterations of the lymphocyte subsets and cytokines in women with advanced endometriosis may have an impact on the oocyte development and resulting in poorer IVF outcomes.


Subject(s)
Endometriosis , Infertility, Female , Pregnancy , Humans , Female , Follicular Fluid/metabolism , Endometriosis/metabolism , Infertility, Female/metabolism , CD8-Positive T-Lymphocytes/metabolism , Chemokine CXCL10/metabolism , Fertilization in Vitro/methods , Cytokines/metabolism
5.
J Assist Reprod Genet ; 39(3): 719-728, 2022 Mar.
Article in English | MEDLINE | ID: mdl-35119551

ABSTRACT

PURPOSE: Congenital bilateral absence of the vas deferens (CBAVD) is a major cause of obstructive azoospermia and male factor infertility. CBAVD is mainly caused by mutations in the genes encoding CFTR (cystic fibrosis transmembrane conductance regulator) and ADGRG2 (adhesion G protein-coupled receptor G2). This study aimed to describe CFTR and ADGRG2 variations in 46 Chinese CBAVD patients and evaluated sperm retrieval and assisted reproductive technology outcomes. METHODS: The CFTR and ADGRG2 genes were sequenced and analyzed by whole-exome sequencing (WES), and variations were identified by Sanger sequencing. Bioinformatic analysis was performed. We retrospectively reviewed the outcomes of patients undergoing sperm retrieval surgery and intracytoplasmic sperm injection (ICSI). RESULTS: In total, 35 of 46 (76.09%) patients carried at least one variation in CFTR, but no copy number variants or ADGRG2 variations were found. In addition to the IVS9-5 T allele, there were 27 CFTR variations, of which 4 variations were novel and predicted to be damaging by bioinformatics. Spermatozoa were successfully retrachieved in 46 patients, and 39 of the patients had their own offspring through ICSI. CONCLUSION: There are no obvious hotspot CFTR mutations in Chinese CBAVD patients besides the IVS9-5 T allele. Therefore, WES might be the best detection method, and genetic counseling should be different from that provided to Caucasian populations. After proper counseling, all patients can undergo sperm retrieval from their epididymis or testis, and most of them can have their own children through ICSI.


Subject(s)
Infertility, Male , Male Urogenital Diseases , Child , China , Cystic Fibrosis Transmembrane Conductance Regulator/genetics , Humans , Infertility, Male/genetics , Male , Male Urogenital Diseases/genetics , Mutation/genetics , Retrospective Studies , Sperm Injections, Intracytoplasmic , Vas Deferens/abnormalities
6.
Am J Mens Health ; 16(1): 15579883221074816, 2022.
Article in English | MEDLINE | ID: mdl-35176914

ABSTRACT

With the global epidemic of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and the increasing number of infections, little is known about how SARS-CoV-2 affects the male reproductive system during infection or after recovery. Based on the existing research data, we reviewed the effects of SARS-CoV-2 on the male reproductive system and discussed its possible mechanism of action. SARS-CoV-2 enters host cells through the angiotensin-converting enzyme 2 (ACE2)/transmembrane serine protease 2 (TMPRSS2) pathway, and males are more susceptible than females. After infection, immunopathological damage is noticed in the testicles, and the semen index is significantly reduced. Second, abnormalities of serum follicle-stimulating hormone (FSH), luteinizing hormone (LH), and testosterone (T) levels were also observed, suggesting that there may be dysfunction of the hypothalamic-pituitary-gonadal (HPG) axis. Even after recovery, the effect of SARS-CoV-2 on the male reproductive system can last for at least a period. There are still many unresolved questions about the effect of SARS-CoV-2 infection on the male reproductive tract. Other receptors involved during the invasion of human cells by SARS-CoV-2 remain to be identified. Will the mutation of SARS-CoV-2 increase the diversity of receptors? How does SARS-CoV-2 affect the HPG axis? The long-term effects of SARS-CoV-2 on the male reproductive system remain to be evaluated. SARS-CoV-2 infection can affect male reproductive function. Standard treatment strategies should be developed in time to protect the fertility of infected patients. For recovered patients with fertility requirements, fertility assessments should be performed and professional fertility guidance should be provided at the same time.


Subject(s)
COVID-19 , Female , Genitalia, Male , Humans , Male , Reproduction , SARS-CoV-2 , Testis
7.
J Enzyme Inhib Med Chem ; 36(1): 1905-1915, 2021 Dec.
Article in English | MEDLINE | ID: mdl-34369236

ABSTRACT

Epidermal growth factor receptor (EGFR) signalling and the interleukin-6 (IL-6)/signal transducer and activator of transcription 3 (STAT3) are aberrantly activated in ovarian cancer. However, inhibition of EGFR signalling in ovarian cancer patients resulted in a disappointing clinical benefit. In this study, we found that EGFR could activate IL-6-STAT3 pathway in ovarian cancer cells. However, we also demonstrated that EGFR knockdown could increase STAT3 phosphorylation in HO8910 and OVCAR-3 ovarian cancer cells. Interestingly, we further demonstrated that the non-coding RNA miR-146b could simultaneously block both the EGFR and IL-6-STAT3 pathways. Finally, our data demonstrated that miR-146b overexpression resulted in a greater suppression of cell migration than STAT3 pathway inhibition alone.These results suggest a complex and heterogeneous role of EGFR in ovarian cancer. Combined blockade of EGFR and IL-6-STAT3 pathways by miR-146b might be a strategy for improving the clinical benefit of targeting the EGFR pathway in ovarian cancer patients in the future.


Subject(s)
Carcinoma, Ovarian Epithelial/metabolism , ErbB Receptors/metabolism , Interleukin-6/metabolism , MicroRNAs/metabolism , Ovarian Neoplasms/metabolism , STAT3 Transcription Factor/metabolism , Cell Line, Tumor , Cell Movement , Cell Proliferation , ErbB Receptors/genetics , Female , Gene Expression Regulation , Gene Knockdown Techniques , Humans , Phosphorylation , Signal Transduction
8.
Am J Reprod Immunol ; 86(2): e13406, 2021 08.
Article in English | MEDLINE | ID: mdl-33629434

ABSTRACT

PROBLEM: During the first trimester, the accumulation of macrophages, which is the second largest decidual leukocyte population (~20%) at the maternal-fetal interface, is quite vital for a successful pregnancy, including embryo implantation, trophoblast invasion, and vascular remodeling. The mechanism of the enrichment and redistribution of macrophages in the uterine decidua of early pregnancy is largely unclear. METHOD OF STUDY: A total of 37 women with normal early pregnancies were included. Primary decidual macrophages (dMφs) (n = 37) and primary decidual stromal cells (DSCs) (n = 37) were isolated, and the adhesion molecules were analyzed by flow cytometry (FCM). Adhesive experiment was carried out to evaluate the adhesion capacity by counting cell numbers of dMφs adhered to DSCs in a co-culture system. RESULTS: We found that RANK+ dMφs was the dominating subtype at the maternal-fetal interface. The expression of adhesion molecules (eg, CD29, CD31, CD54, and CD62L) on the surface of RANK+ dMφs was higher than that of RANK- dMφs. After co-culture with DSCs, the expression of adhesion molecules on dMφs was up-regulated in a RANKL-dependent manner. Meanwhile, dMφs promoted the releasing of RANKL on DSCs after co-culture. Consistently, dMφs exhibited the lessoned capacity of adhesion to DSCs when blocking the crosstalk of RANKL-RANK between the DSCs and dMφs in vitro. CONCLUSION: These results suggest that the interaction of RANKL-RANK up-regulates the expression of adhesion molecules on the surface of dMφs, contributing to the accumulation and residence of dMφs in human early pregnancy.


Subject(s)
Decidua/metabolism , Macrophages/metabolism , Pregnancy Trimester, First/metabolism , Pregnancy/metabolism , RANK Ligand/metabolism , Adult , Female , Humans , Stromal Cells
9.
Am J Mens Health ; 14(5): 1557988320970053, 2020.
Article in English | MEDLINE | ID: mdl-33131385

ABSTRACT

Reproductive tract inflammation is considered an important cause of male infertility. Increased leukocytes in semen can produce many reactive oxygen species (ROS), which affect sperm function. The aim of this study is to identify the main source of ROS in seminal plasma and to assess the effect of ROS on leukocytes. Semen samples (n = 20) with leukocyte concentration >1 × 106 were collected from a male infertility clinic. This study mainly compares the sperm function parameters of the normal group and the semen white blood cell group >1 × 106. The results identified that ROS in semen was closely related to sperm function parameters, and CD45+ leucocytes were the main source of ROS. Compared with the control group, the concentration of IL-2, IL-4, IL-6, IFN-γ, and TNF-α was higher in the experimental group. Leukocytes in semen may regulate the secretion of ROS through the mammalian target of rapamycin (mTOR) pathway. A considerable amount of ROS can upregulate the expression of IL-6 in leukocytes via the nuclear factor kappa-B (NF-kB) pathway.


Subject(s)
Infertility, Male/metabolism , Oxygen/metabolism , Reactive Oxygen Species , Semen/metabolism , Spermatozoa/metabolism , Humans , Interleukin-6 , Leukocytes , Male
10.
Reprod Biol ; 20(4): 460-464, 2020 Dec.
Article in English | MEDLINE | ID: mdl-32798137

ABSTRACT

In the past, semen parameters have been the primary diagnostic criteria used to establish male infertility. However, with the exception of sperm motility, which is known to be linked to rates of in vitro fertilization success, these parameters are generally unreliable at accurately predicting the potential fertility of a couple. More recent research has suggested that sperm DNA fragmentation index (DFI) may be a more robust and reliable means of predicting assisted reproductive outcomes. The present study aimed to assess the relationship between sperm motility, sperm DFI, and rates of clinical pregnancy by analyzing data from 3000 couples dealing with infertility. Using the most recent semen analysis reports available from male partners in these couples, we assessed these parameters and found that the lower the sperm DFI value, the higher the rate of clinical pregnancy. When we assessed the correlation between sperm DFI, sperm motility, and clinical pregnancy, we observed a strong negative correlation between DFI and motility, but observed no significant relationship between sperm motility and pregnancy rates. These results thus indicate that the measurement of DFI via a sperm chromatin structure assay (SCSA) may be a valuable tool for analyzing semen in order to better predict and improve pregnancy rates in infertile couples.


Subject(s)
Chromatin/ultrastructure , DNA Fragmentation , Pregnancy Rate , Reproductive Techniques, Assisted , Sperm Motility , Spermatozoa/ultrastructure , Adult , Female , Humans , Male , Pregnancy , Retrospective Studies , Semen Analysis
11.
Gynecol Endocrinol ; 35(11): 985-990, 2019 Nov.
Article in English | MEDLINE | ID: mdl-31124382

ABSTRACT

Oocytes are extremely sensitive to radiation and chemotherapy, and premature ovarian failure (POF) is one of the side effects of anti-tumor therapy. The pathogenesis of POF is very complex and still not fully elucidated. A mouse POF model was established after 14 days of cyclophosphamide injection. POF mice presented ovarian atrophy, destroyed follicular structure, a reduction in the number of primordial and mature follicles, and an decrease in the number of corpora luteal along with increased level of follicle-stimulating hormone (FSH), decreased levels of estradiol (E2), and anti-Mullerian hormone (AMH). Additionally, the proportion of bone marrow myeloid-derived suppressor cells (MDSCs) in peripheral blood, spleen, and ovarian tissue increased. MDSCs were mainly distributed around follicles and corpora luteal. Levels of mTOR and p-mTOR increased in ovarian tissue and inhibition of mTOR with rapamycin reduced the aggregation of MDSCs in peripheral blood, spleen, and ovarian tissue. This investigation sheds new light on the modulatory role of mTOR and demonstrates that an increase in MDSC number may play a key role in the pathological reaction during POF. Inhibition of mTOR and reduction of MDSCs in the ovary may represent a novel strategy for the treatment of POF.


Subject(s)
Myeloid-Derived Suppressor Cells/drug effects , Ovary/drug effects , Ovary/pathology , Primary Ovarian Insufficiency/chemically induced , TOR Serine-Threonine Kinases/metabolism , Animals , Cell Aggregation/drug effects , Cyclophosphamide , Disease Models, Animal , Female , Ovary/metabolism , Primary Ovarian Insufficiency/metabolism , Primary Ovarian Insufficiency/pathology , Weight Loss
12.
Reproduction ; 157(2): 189-198, 2019 02 01.
Article in English | MEDLINE | ID: mdl-30605433

ABSTRACT

There is delicate crosstalk between fetus-derived trophoblasts (Tros) and maternal cells during normal pregnancy. Dysfunctions in interaction are highly linked to some pregnancy complications, such as recurrent spontaneous abortion (RSA), pre-eclampsia and fetal growth restriction. Hyaluronan (HA), the most abundant component of extracellular matrix, has been reported to act as both a pro- and an anti-inflammatory molecule. Previously, we reported that HA promotes the invasion and proliferation of Tros by activating PI3K/Akt and MAPK/ERK1/2 signaling pathways. While lower HA secretion by Tros was observed during miscarriages than that during normal pregnancies, in the present study, we further confirmed that higher secretion of HA by Tros could induce M2 polarization of macrophages at the maternal-fetal interface by interacting with CD44 and activating the downstream PI3K/Akt-STAT-3/STAT-6 signaling pathways. Furthermore, HA could restore the production of IL-10 and other normal pregnancy markers by decidual macrophages (dMφs) from RSA. These findings underline the important roles of HA in regulating the function of dMφs and maintaining a normal pregnancy.


Subject(s)
Decidua/metabolism , Hyaluronic Acid/metabolism , Macrophages/metabolism , Trophoblasts/metabolism , Abortion, Habitual/metabolism , Cell Proliferation/physiology , Decidua/cytology , Female , Humans , Macrophages/cytology , Mitogen-Activated Protein Kinases/metabolism , Phosphatidylinositol 3-Kinases/metabolism , Signal Transduction
13.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 35(4): 515-517, 2018 Aug 10.
Article in Chinese | MEDLINE | ID: mdl-30098246

ABSTRACT

OBJECTIVE: To detect FOXL2 gene mutation in a Chinese pedigree affected with blepharophimosis-ptosis-epicanthus inversus syndrome (BPES) type I, and to explore its genotype-phenotype correlation. METHODS: Peripheral blood samples were obtained from 3 patients and 19 healthy members from the pedigree for the isolation of genomic DNA. All exons and flanking sequences of the FOXL2 gene were amplified by PCR with 7 pairs of overlapping primers and sequenced. RESULTS: DNA sequencing indicated that the BPES phenotype in this pedigree was caused by a hotspot c.843_859dup17 mutation. The same mutation was not found among the healthy members of the pedigree. CONCLUSION: The c.843_859dup17 frameshift mutation probably underlies the BPES type I in this Chinese pedigree, which may manifest as either BEPS type I or type II.


Subject(s)
Blepharophimosis/genetics , Blepharoptosis/genetics , Forkhead Box Protein L2/genetics , China , Genetic Association Studies , Humans , Mutation , Pedigree , Syndrome
14.
Zhonghua Nan Ke Xue ; 24(2): 147-151, 2018 Feb.
Article in Chinese | MEDLINE | ID: mdl-30156075

ABSTRACT

OBJECTIVE: To investigate the prevalence of Ureaplasma urealyticum (UU) infection in infertile men, its influence on routine semen parameters and the distribution of antisperm antibody (AsAb) and its types in infertile patients with UU infection. METHODS: We detected the positive rate of UU infection, semen parameters, and the distribution of AsAb and its types in 662 infertile men and 25 normal fertile male controls followed by comparison of the obtained data between the two groups of subjects. RESULTS: The positive rate of UU infection was significantly higher in the infertile men than in the normal controls (52.87% ï¼»350/662ï¼½ vs 16.00% ï¼»4/25ï¼½, χ2 = 11.68, P <0.05). The semen volume, sperm count, sperm concentration and percentage of progressively motile sperm were remarkably lower in the UU-positive infertile males than in the control group (P <0.05). No statistically significant difference was observed between the UU-positive and UU-negative groups in the positive rates of total AsAb (43.4% vs 36.5%, χ2 = 3.25, P >0.05) and AsAb IgA, IgM and IgG in the seminal plasma, or in the percentages of serum AsAb IgM (16.9% vs 20.5%, χ2 = 1.22, P >0.05) and IgG (32.7% vs 28.9%, χ2 = 0.99, P >0.05) except in that of serum AsAb IgA (23.6% vs 17.0%, χ2 = 4.03, P <0.05). CONCLUSIONS: The UU infection rate is high in infertile males, which decreases the semen volume, total sperm count, motile sperm concentration and percentage of progressively motile sperm and increases the positive rate of serum AsAb IgA.


Subject(s)
Antibodies, Bacterial/analysis , Infertility, Male/microbiology , Spermatozoa/immunology , Ureaplasma Infections/diagnosis , Ureaplasma urealyticum/immunology , Humans , Infertility, Male/immunology , Male , Semen , Sperm Count , Ureaplasma Infections/immunology
15.
Zhonghua Nan Ke Xue ; 23(4): 329-336, 2017 Apr.
Article in Chinese | MEDLINE | ID: mdl-29714418

ABSTRACT

OBJECTIVE: Sperm DNA fragmentation (SDF) is widely used to predict male infertility and the methods of detecting SDF are varied. This study aimed to compare two methods of SDF detection and investigate the correlation between SDF and sperm quality. METHODS: Using sperm chromatin structure assay (SCSA) and sperm chromatin dispersion test (SCD), we detected SDF in 108 semen samples collected in the Center of Reproduction and Genetics of Suzhou Municipal Hospital. We compared the results of the two methods and analyzed the correlations of SDF routine semen parameters, sperm morphology and the age of the patients. RESULTS: A significant consistency was found in the SDF index (DFI) between the two methods (P<0.01). The DFI was correlated negatively with sperm motility, the percentage of progressively motile sperm, and that of morphologically normal sperm (P <0.01), but positively with the teratozoospermia index (P <0.01 in SCSA and P <0.05 in SCD). The DFI measured by SCSA showed a significantly positive correlation with the patients' age (P <0.01), but not that obtained by SCD. CONCLUSIONS: The results of both SCSA and SCD play an important role in predicting sperm quality. As a clinical index, the DFI has a predictive value for male infertility. However, the results of different detecting methods vary widely, which calls for further studies on their standardization.


Subject(s)
Chromatin/physiology , DNA Fragmentation , Infertility, Male/diagnosis , Semen/physiology , Spermatozoa/physiology , Chromatin/genetics , Humans , Male , Semen Analysis , Sperm Motility , Spermatozoa/ultrastructure
16.
Int Immunopharmacol ; 40: 1-10, 2016 Nov.
Article in English | MEDLINE | ID: mdl-27567245

ABSTRACT

Epidemiological studies have shown that fat rich western diet contributes to the high incidence of inflammatory bowel disease (IBD). Moreover, accumulated data indicated that fat dietary factor might promote the change of the composition and metabolism in commensal flora. But, the exact mechanisms for fatty diet in gut inflammation are not well demonstrated. In this study, we found that high fat diet (HFD) promoted inflammation and exacerbated the disease severity of dextran sulfate sodium (DSS) induced colitis in mice. Compared with low fat diet (LFD)/DSS mice, shorter colon length, more epithelial loss and crypt destruction and more Gr-1+ myeloid inflammatory cells infiltration in colons were observed in HFD/DSS cohorts. Interestingly, such HFD mediated inflammation accompanied with the dys-regulation of hematopoiesis, and more hematopoiesis stem and progenitor cells were detected in colon and spleen. We further analyzed the effects of HFD and DSS treatment on mucosal DC subsets, and found that DSS treatment in LFD mice mainly dramatically increased the percentage of CD11c+CD103-CD11b+ DCs in lamina propria (LP). While, in HFD/DSS mice, HFD pre-treatment not only increased the percentage of CD11c+CD103-CD11b+ DCs, but also decreased CD11c+CD103+CD11b+ in both LP and mesenteric lymph nodes (MLN) in mice with colitis. This disequilibrium of mucosal dendritic cells in HFD/DSS mice may depend on the reduced levels of buytrate and retinoic acid. Thus, this study declared the effects of HFD on gut microenviroment, and further indicated its potential role in the development of DSS induced colitis.


Subject(s)
Colitis/immunology , Colitis/pathology , Dendritic Cells/immunology , Diet, High-Fat/adverse effects , Intestinal Mucosa/immunology , Animals , Antigens, CD/immunology , Butyrates/metabolism , Cecum/metabolism , Colitis/chemically induced , Colon/immunology , Colon/pathology , Dextran Sulfate , Homeostasis , Intestinal Mucosa/pathology , Male , Mice, Inbred C57BL , Tretinoin/metabolism
17.
Endocrinology ; 156(8): 2821-30, 2015 Aug.
Article in English | MEDLINE | ID: mdl-26061726

ABSTRACT

The self-renewal and differentiation of hematopoietic stem cells (HSCs) in bone marrow are essential to replenish all blood cell types, but how this process is influenced by diet remains largely unclear. Here we show that a diet rich in fish oils promotes self-renewal of HSCs and extramedullary hematopoiesis. Chronic intake of a fish oil-rich diet increases the abundance of HSCs, alters the hematopoietic microenvironment, and, intriguingly, induces the expression of matrix metalloproteinase 12 (MMP12) in the bone marrow. Pointing to a direct effect of fish oil on MMP12 expression, omega-3 polyunsaturated fatty acids induce the expression of MMP12 in a dose-dependent manner in bone marrow cells. Importantly, down-regulation of MMP12 activity using an MMP12-specific inhibitor attenuates diet-induced myelopoiesis in both bone marrow and spleen. Thus, a fish oil-rich diet promotes hematopoiesis in the bone marrow and spleen, in part via the activity of MMP12. Taken together, these data provide new insights into diet-mediated regulation of hematopoiesis.


Subject(s)
Diet , Fish Oils/pharmacology , Hematopoiesis/drug effects , Hematopoietic Stem Cells/drug effects , Stem Cell Niche/drug effects , Animals , Bone Marrow Cells/drug effects , Bone Marrow Cells/physiology , Cell Proliferation/drug effects , Cells, Cultured , Fatty Acids, Omega-3/pharmacology , Hematopoiesis, Extramedullary/drug effects , Hematopoietic Stem Cells/cytology , Male , Mice , Mice, Inbred C57BL , Spleen/cytology , Spleen/drug effects
18.
Cancer Immunol Immunother ; 63(7): 663-73, 2014 Jul.
Article in English | MEDLINE | ID: mdl-24691944

ABSTRACT

Omega-3 polyunsaturated fatty acids enriched fish oil exerts beneficial anti-inflammatory effects in animal models with acute and chronic inflammatory diseases. Myeloid-derived suppressor cells (MDSCs), comprised of myeloid progenitors and precursors of myeloid cells, play vital roles in cancer. How fish oil affects the generation of MDSCs and the tumor development remains largely unexplored. Here, we show that dietary intake of high fish oil diet suppresses CD8(+) T cells activation and proliferation in vivo via elevated levels of MDSCs. Mechanistically, high fish oil diet induces the expression of immunosuppressive cytokine IL-10 and promotes myelopoiesis in the spleen as well as other peripheral tissues. The immature myeloid cells in the spleen exhibit morphological and functional characteristics of MDSCs with the capability to downregulate CD8(+) T cells activation. Depletion of MDSCs using anti-Gr-1 antibody decreases the growth of subcutaneously transferred B16 melanoma in mice on high fish oil diet. Interestingly, diet-induced production of MDSCs is not solely dependent of the spleen, as splenectomy has no effect on the tumor progress. Our data show that the liver functions as an alternative extramedullary hematopoiesis organ to support MDSCs differentiation and maintain tumor growth. Taken together, our study provides a novel insight into the physiological effects of fish oil and points to MDSCs as a possible mediator linking dietary fish oil intake and immunosuppression in cancer immunosurveillance.


Subject(s)
Fatty Acids, Omega-3/administration & dosage , Fatty Acids, Omega-3/adverse effects , Melanoma, Experimental/pathology , Myeloid Cells/pathology , Animals , Antigen Presentation/drug effects , CD8 Antigens/metabolism , Cell Growth Processes/drug effects , Lymphocyte Activation/drug effects , Mice , Mice, Inbred C57BL , Myeloid Cells/immunology , Myeloid Cells/metabolism , Spleen/drug effects , Spleen/metabolism , Splenectomy/methods
19.
J Toxicol Sci ; 39(2): 179-90, 2014 Apr.
Article in English | MEDLINE | ID: mdl-24646698

ABSTRACT

The development of hepatitis is associated with the infiltration and activation of immune cells in liver. N-3 polyunsaturated fatty acids (n-3 PUFAs) rich fish oil (FO) is used to prevent and treat inflammatory diseases. But, the effects of dietary FO on autoimmune hepatitis remain largely unknown. In this study, Concanavalin A (Con A) induced hepatitis was used to evaluate the actions of dietary FO. Unexpectedly, 2-week FO treatment had not shown any protection, on the contrary, exacerbated liver injury in this hepatitis model. The levels of alanine aminotransferase (ALT) and lactate dehydrogenase (LDH) statistically increased from 10,501 ± 2,154 and 30,394 ± 2,420 in low fat diet (LFD)/Con A group to 17,579 ± 693 and 49,439 ± 4,628 in FO/Con A group. Simultaneously, FO diet induced more necrotic liver tissues and apoptotic hepatocytes, and up-regulated the hepatic expression of TNF-α and IFN-γ after Con A challenge. Interestingly, FO promoted severe liver injury was accompanied by decreasing the percentage of CD4⁺ T cell, NK1.1⁺ cells and CD8⁺ T cells in CD45⁺ liver non-parenchymal hepatic cells (NPCs) through inducing apoptosis. Further experiments declared 2-week FO diet intake firstly increased the proportion of CD11b⁺Gr-1(hi) neutrophils in liver, but then dramatically expanded CD11b⁺Gr-1(int) inflammatory monocytes population after Con A administration. Collectively, our study indicated that high FO intake not only aggravated liver injury, but also altered the population of immune cells in liver. Thus, these results indicated that when dietary FO was used to benefit health in autoimmune diseases, its potential risks of side effect also need paying close attention.


Subject(s)
Apoptosis , Chemical and Drug Induced Liver Injury/pathology , Concanavalin A/pharmacology , Fatty Acids, Omega-3/adverse effects , Fish Oils/adverse effects , Hepatitis, Autoimmune/pathology , Hepatocytes/pathology , Liver/immunology , Alanine Transaminase/metabolism , Animals , Apoptosis/immunology , CD11b Antigen , CD4-Positive T-Lymphocytes/pathology , CD8-Positive T-Lymphocytes/pathology , Chemical and Drug Induced Liver Injury/immunology , Dietary Supplements/adverse effects , Disease Models, Animal , Fish Oils/chemistry , Hepatitis, Autoimmune/immunology , Hepatocytes/drug effects , Hepatocytes/immunology , Hydro-Lyases/metabolism , Interferon-gamma/metabolism , Killer Cells, Natural/pathology , Leukocyte Common Antigens , Liver/cytology , Liver/metabolism , Liver/pathology , Male , Mice , Mice, Inbred C57BL , Neutrophils , Tumor Necrosis Factor-alpha/metabolism
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