Extraislet expression of islet antigen boosts T cell exhaustion to partially prevent autoimmune diabetes.

Persistent antigen exposure results in the differentiation of functionally impaired, also termed exhausted, T cells which are maintained by a distinct population of precursors of exhausted T (TPEX) cells. T cell exhaustion is well studied in the context of chronic viral infections and cancer, but it is unclear whether and how antigen-driven T cell exhaustion controls progression of autoimmune diabetes and whether this process can be harnessed to prevent diabetes. Using nonobese diabetic (NOD) mice, we show that some CD8+ T cells specific for the islet antigen, islet-specific glucose-6-phosphatase catalytic subunit-related protein (IGRP) displayed terminal exhaustion characteristics within pancreatic islets but were maintained in the TPEX cell state in peripheral lymphoid organs (PLO). More IGRP-specific T cells resided in the PLO than in islets. To examine the impact of extraislet antigen exposure on T cell exhaustion in diabetes, we generated transgenic NOD mice with inducible IGRP expression in peripheral antigen-presenting cells. Antigen exposure in the extraislet environment induced severely exhausted IGRP-specific T cells with reduced ability to produce interferon (IFN)γ, which protected these mice from diabetes. Our data demonstrate that T cell exhaustion induced by delivery of antigen can be harnessed to prevent autoimmune diabetes.

CCDC189 depletion leads to oligo-astheno-teratozoospermia and male infertility in mice.

In male reproductive system, proteins containing the coiled-coil domain (CCDC) are predominantly expressed in specific regions including the testis, epididymis, seminal vesicle, and prostate. They play a vital role in centriole formation, sperm motility and flagellar development in male gametes. Despite being highly expressed in the testis, the exact physiological function of the coiled-coil domain-containing 189 (Ccdc189) gene remain largely unclear. Our research provides a comprehensive and detailed investigation into the localization of CCDC189 protein within the testis seminiferous tubules. CCDC189 specifically expressed in spermatocytes, round spermatids and elongating spermatids in mouse testis. The deletion of Ccdc189 in mouse leads to male infertility, characterized by significantly reduced sperm counts and motility. Abnormally shaped spermatozoa with irregular tails, exhibiting shortened and twisted morphology, were observed in the seminiferous tubules. Electron microscopy revealed disordered and missing peripheral microtubule doublets (MTD) and outer dense fibers (ODF) in the sperm flagella, accompanied by a consistent absence of central pairs (CP). The knockout of Ccdc189 resulted in oligo-astheno-teratozoospermia, which is characterized by low sperm count and reduced sperm motility and abnormal morphology. Furthermore, we identified poly(A)-binding protein cytoplasmic 1 (PABPC1) and PABPC2 as interacting proteins with CCDC189. These proteins belong to the poly(A)-binding protein (PABP) family and are involved in regulating mRNA translational activity in spermatogenic cells by specifically binding to poly(A) tails at the 3' ends of mRNAs.

Coiled-coil domain containing 159 is required for spermatid head and tail assembly in mice†.

The centrosome is critical for maintaining the sperm head-tail connection and the formation of flagellar microtubules. In this study, we found that in mouse testes, CCDC159 (coiled-coil domain-containing protein 159) is specifically localized to the head-tail coupling apparatus (HTCA) of spermatids, a structure that ensures sperm head-tail tight conjunction. CCDC159 contains a C-terminal coiled-coil domain that functions as the centrosomal localization signal. Gene knockout (KO) of Ccdc159 in mice resulted in acephalic spermatozoa, abnormal flagella, and male infertility. To explore the mechanism behind CCDC159 regulating spermatogenesis, we identified CCDC159-binding proteins using a yeast two-hybrid screen and speculated that CCDC159 participates in HTCA assembly by regulating protein phosphatase PP1 activity. Further RNA-sequencing analyses of Ccdc159 KO testes revealed numerous genes involved in male gamete generation that were downregulated. Together, our results show that CCDC159 in spermatids is a novel centrosomal protein anchoring the sperm head to the tail. Considering the limitation of KO mouse model in clarifying the biological function of CCDC159 in spermatogenesis, a gene-rescue experiment will be performed in the future.

Association of previous stillbirth with subsequent perinatal outcomes: a systematic review and meta-analysis of cohort studies.

OBJECTIVE: We conducted a systematic review and meta-analysis to examine the relationship between stillbirth and various perinatal outcomes in subsequent pregnancy. DATA SOURCES: PubMed, the Cochrane Library, Embase, Web of Science, and CNKI databases were searched up to July 2023. STUDY ELIGIBILITY CRITERIA: Cohort studies that reported the association between stillbirth and perinatal outcomes in subsequent pregnancies were included. METHODS: We conducted this systematic review and meta-analysis in accordance with the PRISMA guidelines. Statistical analysis was performed using R and Stata software. We used random-effects models to pool each outcome of interest. We performed a meta-regression analysis to explore the potential heterogeneity. The certainty (quality) of evidence assessment was performed using the GRADE approach. RESULTS: Nineteen cohort studies were included, involving 4,855,153 participants. From these studies, we identified 28,322 individuals with previous stillbirths who met the eligibility criteria. After adjusting for confounders, evidence of low to moderate certainty indicated that compared with women with previous live births, women with previous stillbirths had higher risks of recurrent stillbirth (odds ratio, 2.68; 95% confidence interval, 2.01-3.56), preterm birth (odds ratio, 3.15; 95% confidence interval, 2.07-4.80), neonatal death (odds ratio, 4.24; 95% confidence interval, 2.65-6.79), small for gestational age/intrauterine growth restriction (odds ratio, 1.3; 95% confidence interval, 1.0-1.8), low birthweight (odds ratio, 3.32; 95% confidence interval, 1.46-7.52), placental abruption (odds ratio, 3.01; 95% confidence interval, 1.01-8.98), instrumental delivery (odds ratio, 2.29; 95% confidence interval, 1.68-3.11), labor induction (odds ratio, 4.09; 95% confidence interval, 1.88-8.88), cesarean delivery (odds ratio, 2.38; 95% confidence interval, 1.20-4.73), elective cesarean delivery (odds ratio, 2.42; 95% confidence interval, 1.82-3.23), and emergency cesarean delivery (odds ratio, 2.35; 95% confidence interval, 1.81-3.06) in subsequent pregnancies, but had a lower rate of spontaneous labor (odds ratio, 0.22; 95% confidence interval, 0.13-0.36). However, there was no association between previous stillbirth and preeclampsia (odds ratio, 1.72; 95% confidence interval, 0.63-4.70) in subsequent pregnancies. CONCLUSION: Our systematic review and meta-analysis provide a more comprehensive understanding of adverse pregnancy outcomes associated with previous stillbirth. These findings could be used to inform counseling for couples who are considering pregnancy after a previous stillbirth.

A spatiotemporal atlas of organogenesis in the development of orchid flowers.

Development of floral organs exhibits complex molecular mechanisms involving the co-regulation of many genes specialized and precisely functioning in various tissues and developing stages. Advance in spatial transcriptome technologies allows for quantitative measurement of spatially localized gene abundance making it possible to bridge complex scenario of flower organogenesis with genome-wide molecular phenotypes. Here, we apply the 10× Visium technology in the study of the formation of floral organs through development in an orchid plant, Phalaenopsis Big Chili. Cell-types of early floral development including inflorescence meristems, primordia of floral organs and identity determined tissues, are recognized based on spatial expression distribution of thousands of genes in high resolution. In addition, meristematic cells on the basal position of floral organs are found to continuously function in multiple developmental stages after organ initiation. Particularly, the development of anther, which primordium starts from a single spot to multiple differentiated cell-types in later stages including pollinium and other vegetative tissues, is revealed by well-known MADS-box genes and many other downstream regulators. The spatial transcriptome analyses provide comprehensive information of gene activity for understanding the molecular architecture of flower organogenesis and for future genomic and genetic studies of specific cell-types.

Basilar artery curvature increases the risk of posterior circulation infarction occurrence in patients without vertebrobasilar stenosis.

INTRODUCTION: Limited cross-sectional or case-control studies have identified the relationship between basilar artery (BA) curvature and posterior circulation infarction (PCI). This study aimed to identify the influence of BA curvature severity on the risk of PCI occurrence in patients without vertebrobasilar stenosis through a prospective cohort study. METHODS: In this study, we enrolled 171 patients with BA dolichosis but without vertebrobasilar stenosis. The BA geometric parameters were evaluated on MRA. The primary outcome was the occurrence of PCI, mainly referring to cerebellar and/or brainstem infarction. Cox proportional hazard models were used to detect possible predictors of PCI. RESULTS: Among them, 134 (78.4%) patients were diagnosed with BA curvature, including 124 with moderate curvature and 10 with prominent curvature. The defined PCI occurrence was observed in 32 (18.7%) patients with a median follow-up time of 45.6 months. Cox proportional hazard analysis showed that BA prominent curvature (HR = 6.09; 95% CI: 1.36-27.28; P = 0.018) significantly increased the risk of PCI occurrence, and bending length (BL) was also significantly associated with PCI occurrence, with the adjusted HR per 1-mm increase of BL of 1.09 (95% CI: 1.01-1.18; P = 0.040). In the subgroup analysis stratified by age, BA prominent curvature was highly associated with PCI occurrence in patients aged > 61 years (HR = 11.76; 95% CI: 1.21-113.90; P = 0.033). Additionally, good antiplatelet therapy adherence could significantly reduce the risk of PCI occurrence. CONCLUSION: BA curvature may increase the risk of PCI occurrence, especially in elderly patients with prominent curvature. Improving adherence to antiplatelet therapy can help reduce the risk of PCI occurrence.

MicroRNA-302 represses epithelial-mesenchymal transition and cisplatin resistance by regulating ATAD2 in ovarian carcinoma.

Epithelial-mesenchymal transition (EMT) is an important contributor to drug resistance in ovarian cancer. The aims of this study were to explore the potential role of the miR-302 cluster in modulating EMT and cisplatin resistance in ovarian cancer. We used qRT-PCR and western blotting to show that miR-302 expression was lower in chemoresistant than in chemosensitive cells, and miR-302 was upregulated in chemosensitive, but not chemoresistant ovarian cancer cells in response to cisplatin treatment. We identified ATAD2 as a target of miR-302 and showed that ectopic expression of miR-302 increased cisplatin sensitivity and inhibited EMT and the invasiveness of cisplatin-resistant cells in vitro by targeting ATAD2. Knockdown of ATAD2 restored cisplatin sensitivity and reversed EMT/metastasis in cisplatin-resistant cells, as shown by western blotting and invasion/migration assays. The effect of miR-302 overexpression on EMT and invasiveness was mediated by the modulation of ß-catenin nuclear expression. Immunofluorescence analysis showed that ATAD2 overexpression reversed the miR-302-induced downregulation of nuclear ß-catenin in cisplatin resistant cells. A xenograft tumor model was used to show that miR-302 increases the antitumor effect of cisplatin in vivo. Taken together, these results identify a potential regulatory axis involving miR-302 and ATAD2 with a role in chemoresistance, indicating that activation of miR-302 or inactivation of ATAD2 could serve as a novel approach to reverse cisplatin resistance in ovarian cancer.

Structural Relationships Between Interstitial Cells of Cajal and Smooth Muscle Cells/Nerve Fibers in the Gastric Muscularis Mucosae of Chinese Giant Salamander.

Interstitial cells of Cajal (ICC) play an essential role in the motility of the gastrointestinal tract, and they have been identified in many laboratory animals and in humans. However, the information of ICC in lower animals is still very limited. In the present study, ICC were identified in the gastric muscularis mucosae of an amphibian­the Chinese giant salamander, by c-Kit immunohistochemistry and transmission electron microscopy. ICC showed c-Kit immunoreactivity and had spindle-shaped cell bodies and 1­2 long processes. ICC were located between smooth muscle cells (SMC) in gastric muscularis mucosae. Ultrastructurally, ICC appeared as polygon-, spindle-, and awl-shaped with long cytoplasmic prolongations between SMC. ICC had distinctive characteristics, such as nuclei with peripheral electron-dense heterochromatin, caveolae, and abundant intracytoplasmatic vacuoles, mitochondria, and rough endoplasmic reticula. Moreover, lamellar bodies and two types of condensed granules were observed in the cytoplasm of ICC. Notably, ICC establish close contacts with each other. Moreover, ICC establish gap junctions with SMC. In addition, ICC were frequently observed close to nerve fibers. In summary, the present study demonstrated the presence of ICC in the gastric muscularis mucosae of the Chinese giant salamander.

Role and mechanism of intraflagellar transport in mammalian spermiogenesis.

Eukaryotic cilia and flagella are evolutionarily conserved organelles that protrude from the cell surface. The unique location and properties of cilia allow them to function in vital processes such as motility and signaling. Ciliary assembly and maintenance rely on intraflagellar transport (IFT). Bidirectional movement of IFT particles composed of IFT-A and IFT-B complexes is powered by kinesin-2 and dynein-2 motors. IFT delivers building blocks between their site of synthesis in the cell body and the ciliary assembly site at the tip of the cilium. The integrity of the flagellum, a specialized organelle of mammalian sperm to generate the motility, is critical for normal sperm function. Recent findings suggest that IFT is indispensable for sperm flagellum formation and male fertility in mice and human. In this review, we summarize the role and mechanisms of IFT proteins during enflagellation in spermiogenesis, thereby discussing the pathological mechanisms of male infertility and providing theoretical basis for the diagnosis and treatment of male infertility.

Absence of Long Noncoding RNA H19 Promotes Childhood Nephrotic Syndrome through Inhibiting ADCK4 Signal.

BACKGROUND Nephrotic syndrome (NS) is a common chronic kidney disease in children characterized by a group of clinical symptoms such as massive proteinuria, hypoproteinemia, high edema, and hyperlipidemia. Despite the tremendous efforts already made, the diagnosis for nephrotic syndrome still remains poor in children. MATERIAL AND METHODS The blood samples from 30 healthy children and 30 children with nephrotic syndrome were collected. The expression of H19 and ADCK4 (which are genes recently identified to play key roles in the development of nephrotic syndrome) in peripheral blood mononuclear cells (PBMCs), were detected by real-time quantitative polymerase chain reaction (RT-qPCR). The expression of ADCK4 was also detected by RT-qPCR or western blot when H19 was overexpressed or knocked down in human primary renal podocytes. Luciferase activity analysis was performed to measure whether H19 could regulate the promoter activity of ADCK4. RNA pull-down. In addition, mass spectrometry assay was used to find the transcription factor which could bind with H19, and RNA immunoprecipitation assay (RIPA) analysis was done to further confirm the interaction between H19 and candidate transcription factor. RESULTS Long noncoding RNA H19 (lncRNA H19) expression was downregulated in PBMCs of children with nephrotic syndrome. ADCK4 was also downregulated. In human primary renal podocytes, overexpression of H19 promoted the expression of ADCK4, while H19 knockdown inhibited it. Furthermore, our study demonstrated that H19 could regulate the promoter activity of ADCK4. Using RNA pull-down and mass spectrometry technology, we found the transcription factor-THAP1 could bind with H19, and the interaction between them was further confirmed by RIPA analysis. CONCLUSIONS H19 expression in blood samples may be a novel marker of the diagnosis of nephrotic syndrome in children.

Association of TNFAIP8 gene polymorphisms with endometrial cancer in northern Chinese women.

BACKGROUND: Tumor necrosis factor-a-induced protein 8 (TNFAIP8) presented a elevated expression in endometrial cancer (EC). However, the relationship of TNFAIP8 gene polymorphisms with EC risk remains unclear. This case-control study aimed to investigate the effect of single nucleotide polymorphisms (SNPs) in TNFAIP8 on northern Chinese women with EC. METHODS: SNP rs11064, rs1045241, and rs1045242 in TNFAIP8 were successfully genotyped in 248 cancer-free controls and 226 ECs by SNaPshot method, respectively. Logistic regression was performed to assess relationship of SNPs with EC risk. The relationships of SNPs with clinicopathological variables were evaluated by Chi-square test or Student's t-test or Fisher's text. RESULTS: The minor alleles of rs11064 in TNFAIP8 were strongly associated with EC risk, with adjust odds ratio (OR) of 1.719 (95% CI 1.180-2.506, P = 0.005). The minor allele of rs1045242 in the TNFAIP8 gene was strongly associated with with EC risk (adjust OR: 1.636, 95% CI 1.107-2.417, P = 0.014). rs11064 SNPs correlated with TNFAIP8 protein expression in EC (P = 0.015). For rs1045242, patients with AG + GG presented higher TNFAIP8 protein expression than that with AA (P = 0.020). It also showed that SNP rs11064 was associated with advanced FIGO stage (P = 0.001), deep myometrial invasion (P = 0.047), and lymph node metastasis (P = 0.048) under the codominant model in ECs. CONCLUSIONS: SNP rs11064 in TNFAIP8 increased EC risk and significantly related with its protein expression in northern Chinese women.

Nanowire assisted repeatable DEP-SERS detection in microfluidics.

Surface enhanced Raman spectroscopy (SERS) detection in microfluidics is an interesting topic for its high sensitivity, miniaturization and online detection. In this work, a SERS detection in microfluidics with the help of the Ag nanowire aggregating based on dielectrophoresis (DEP) is reported. The Raman intensities of molecule in microfluidics is greatly enhanced in the naturally generated nanogaps of Ag nanowire aggregating modulated by DEP. Firstly, the influence of DEP voltage and time on Ag nanowire aggregating is investigated to figure out the optimal condition for SERS. And then, the SERS intensities of methylene blue and rhodamine6G at various concentration with high reproducibility and uniformity are studied. Furthermore, the experiment data demonstrate this DEP-SERS system could be repeated used for different molecule detections. At last, the SERS of melamine is measured to explore its application on food safety. Our work anticipates this nanowire assisted repeatable DEP-SERS detection in microfluidics with high sensitivity could meet the emerging needs in environmental pollution monitoring, food safety evaluation, and so on.

Telocytes in ileum of the Chinese giant salamander: ultrastructural evidence.

Telocytes (TCs) and their telopodes (Tps) have been found in various organs of many mammals, including in lower animals. However, knowledge of TCs in lower animals is still very limited. This study identified TCs and their Tps in the ileum of the Chinese giant salamander, Andrias davidianus (Amphibia: Caudata), by transmission electron microscopy. The TCs/Tps were found near epithelial cells, glandular cells and unmyelinated nerve fibres. Moreover, exosomes were also found to be present in between TCs/Tps and these cells.

Telocytes in pancreas of the Chinese giant salamander (Andrias davidianus).

Telocytes (TCs), novel interstitial cells, have been identified in various organs of many mammals. However, information about TCs of lower animals remains rare. Herein, pancreatic TCs of the Chinese giant salamanders (Andrias davidianus) were identified by CD34 immunohistochemistry (IHC) and transmission electron microscopy (TEM). The IHC micrographs revealed CD34+ TCs with long telopodes (Tps) that were located in the interstitium of the pancreas. CD34+ TCs/Tps were frequently observed between exocrine acinar cells and were close to blood vessels. The TEM micrographs also showed the existence of TCs in the interstitium of the pancreas. TCs had distinctive ultrastructural features, such as one to three very long and thin Tps with podoms and podomers, caveolae, dichotomous branching, neighbouring exosomes and vesicles. The Tps and exosomes were found in close proximity to exocrine acinar cells and α cells. It is suggested that TCs may play a role in the regeneration of acinar cells and α cells. In conclusion, our results demonstrated the presence of TCs in the pancreas of the Chinese giant salamander. This finding will assist us in a better understanding of TCs functions in the amphibian pancreas.

The direct anti-cancer efficacy of Sapylin on breast cancer cells in vitro and in vivo.

OBJECTIVE: On the basis of our previous study in which we studied cancer cells under in vitro and in vivo hypoxia conditions, we have now investigated the anti-cancer efficacy of Sapylin on breast cancer cells in mice and human. MATERIALS AND METHODS: We used different concentrations of Sapylin and the three kinds of breast cancer cells. We used water-soluble tetrazolium salt cell proliferation test (WST-1) to detect changes in cell proliferation and Fluorescein Iothiocyanate-Propidium Iodide (Anexin V FITC-PI) to detect changes in the rate of apoptosis by flow cytometry. We also used reverse transcription-polymerase chain reaction (RT-PCR) to detect possible changes of mRNA expression and used western blot in order to test changes related to protein expression that could lead to cell death. The anti-tumor effect was studied by locally injecting Sapylin into an animal tumor model of breast cancer. We also studied the possible postoperative adverse clinical side effects in 60 female breast cancer patients, stage II-III, aged 25-55 years. The patients underwent a modified, radical operation with smooth incisions which healed well. RESULTS: Sapylin was able to inhibit by 10%-15% the proliferation of all three kinds of breast cancer cells and also to present positive correlation in vivo with some phenomenona which were time and concentration dependent. After applying Sapylin for 48h, the apoptosis rate was significantly increased by 12%-20%. Apoptosis of breast cancer cells may be related to biological effects supporting cells survival, through B-cell lymphoma gene 2 (Bcl-2nd) Ki67 mRNA expression descent and Bcl-2 associated X Protein (Bax mRNA) expression. This process ultimately promotes cell death. At the same time this process also showed a significant anti-tumor effect (50%-60%) in a mice model. We found no significant adverse reactions, the patients had no significant pain and the postoperative wound was partially healed. After 5 days, the drainage was well reduced and remained so more in the study group than in the control group at a range of 20%-30% (P<0.05). CONCLUSION: In our research, Sapylin displayed a strong direct anti-cancer effect in breast cancer cells and supported postoperative recovery. Clinically we noticed an obvious reduction of drainage in contrast with the control group.

Genome-wide identification of SSR and SNP markers from the non-heading Chinese cabbage for comparative genomic analyses.

BACKGROUND: Non-heading Chinese cabbage (NHCC), belonging to Brassica, is an important leaf vegetable in Asia. Although genetic analyses have been performed through conventional selection and breeding efforts, the domestication history of NHCC and the genetics underlying its morphological diversity remain unclear. Thus, the reliable molecular markers representative of the whole genome are required for molecular-assisted selection in NHCC. RESULTS: A total of 20,836 simple sequence repeats (SSRs) were detected in NHCC, containing repeat types from mononucleotide to nonanucleotide. The average density was 62.93 SSRs/Mb. In gene regions, 5,435 SSRs were identified in 4,569 genes. A total of 5,008 primer pairs were designed, and 74 were randomly selected for validation. Among these, 60 (81.08%) were polymorphic in 18 Cruciferae. The number of polymorphic bands ranged from two to five, with an average of 2.70 for each primer. The average values of the polymorphism information content, observed heterozygosity, Hardy-Weinberg equilibrium, and Shannon's information index were 0.2970, 0.4136, 0.5706, and 0.5885, respectively. Four clusters were classified according to the unweighted pair-group method with arithmetic average cluster analysis of 18 genotypes. In addition, a total of 1,228,979 single nucleotide polymorphisms (SNPs) were identified in the NHCC through a comparison with the genome of Chinese cabbage, and the average SNP density in the whole genome was 4.33/Kb. The number of SNPs ranged from 341,939 to 591,586 in the 10 accessions, and the average heterozygous SNPs ratio was ~42.53%. All analyses showed these markers were high quality and reliable. Therefore, they could be used in the construction of a linkage map and for genetic diversity studies for NHCC in future. CONCLUSIONS: This is the first systematic and comprehensive analysis and identification of SSRs in NHCC and 17 species. The development of a large number of SNP and SSR markers was successfully achieved for NHCC. These novel markers are valuable for constructing genetic linkage maps, comparative genome analysis, quantitative trait locus (QTL) mapping, genome-wide association studies, and marker-assisted selection in NHCC breeding system research.

Large-scale profiling of metabolic dysregulation in ovarian cancer.

Ovarian cancer is the leading cause of death in gynecologic malignancies. Profiling of endogenous metabolites has potential to identify changes caused by cancer and provide inspiring insights into cancer metabolism. To systematically investigate ovarian cancer metabolism, we performed metabolic profiling of 448 plasma samples related to epithelial ovarian cancer (EOC) based on ultra-performance liquid chromatography mass spectrometry in both positive and negative modes. These unbiased metabolomic profiles could well distinguish EOC from benign ovarian tumor (BOT) and uterine fibroid (UF). Fifty-three metabolites were identified as specific biomarkers for EOC, and this is the first report of piperine, 3-indolepropionic acid, 5-hydroxyindoleacetaldehyde and hydroxyphenyllactate as metabolic biomarkers of EOC. The AUC values of these metabolites for discriminating EOC from BOT/UF and early-stage EOC from BOT/UF were 0.9100/0.9428 and 0.8385/0.8624, respectively. Meanwhile, our metabolites were able to distinguish early-stage EOC from late-stage EOC with an AUC of 0.8801. Importantly, analysis of dysregulated metabolic pathways extends our current understanding of EOC metabolism. Metabolic pathways in EOC patients are mainly characterized by abnormal phospholipid metabolism, altered l-tryptophan catabolism, aggressive fatty acid ß-oxidation and aberrant metabolism of piperidine derivatives. Together, these metabolic pathways provide a foundation to support cancer development and progression. In conclusion, our large-scale plasma metabolomics study yielded fundamental insights into dysregulated metabolism in ovarian cancer, which could facilitate clinical diagnosis, therapy, prognosis and shed new lights on ovarian cancer pathogenesis.

Stromal cell-derived factor-1 alpha alleviates hypoxic-ischemic brain damage in mice.

Hypoxic-ischemic brain damage (HIBD) is a major cause of acute deaths and chronic nervous system damage. There is good evidence that stromal cell-derived factor-1 alpha (SDF-1α) has been receiving much interest in its role in the treatment of ischemic diseases. Here we aim to investigate the effect of intraperitoneal delivery of SDF-1α after experimental hypoxia-ischemia (HI) and the potentially involved mechanisms. A total of 129 mice were subjected to unilateral carotid artery ligation followed by 2.5 h of hypoxia, randomly assigned to three groups: sham, HI + vehicle and HI + SDF-1α. Mice treated with SDF-1α showed recovery of spatial learning abilities and pathological conditions, decreased number of apoptotic cells, and elevated expression of SDF-1α and its cognate receptor, CXC chemokine receptor-4 (CXCR4). Meanwhile, the increased number of mesenchymal stem cells (MSCs) was found in peripheral blood after SDF-1α treatment. Taken together, the treatment of SDF-1α after HIBD contributed to an improved functional recovery, and this behavioral restoration was paralleled by a reduction of apoptosis and mobilization of MSCs via SDF-1α/CXCR4.