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Platelet-derived growth factor-D (PDGF-D) is highly expressed in immune cells. However, the potential role of PDGF-D in immune system remains thus far unclear. Here, we reveal a novel function of PDGF-D in activating both classical and alternative complement pathways that markedly increase chemokine and cytokine responses to promote macrophage polarization. Pharmacological targeting of the complement C3a receptor using SB290157 alleviated PDGF-D-induced neuroinflammation by blocking macrophage polarization and inhibited pathological choroidal neovascularization. Our study thus suggests that therapeutic strategies targeting both PDGF-D and the complement system may open up new possibilities for the treatment of neovascular diseases.

The CHYR (CHY ZINC-FINGER AND RING FINGER PROTEIN) proteins have been functionally characterized in iron regulation and stress response in Arabidopsis, rice and Populus. However, their roles in soybean have not yet been systematically investigated. Here, in this study, 16 GmCHYR genes with conserved Zinc_ribbon, CHY zinc finger and Ring finger domains were obtained and divided into three groups. Moreover, additional 2–3 hemerythrin domains could be found in the N terminus of Group III. Phylogenetic and homology analysis of CHYRs in green plants indicated that three groups might originate from different ancestors. Expectedly, GmCHYR genes shared similar conserved domains/motifs distribution within the same group. Gene expression analysis uncovered their special expression patterns in different soybean tissues/organs and under various abiotic stresses. Group I and II members were mainly involved in salt and alkaline stresses. The expression of Group III members was induced/repressed by dehydration, salt and alkaline stresses, indicating their diverse roles in response to abiotic stress. In conclusion, our work will benefit for further revealing the biological roles of GmCHYRs.

Background.Tumor immunotherapy and immunological checkpoint-related proteins are research hotspots. Intensity-modulated radiotherapy (IMRT) is the main treatment for nasopharyngeal carcinoma (NPC). Hence, the evaluation of its effect is very important. The aim of this study was to assess the relationship between the concentrations of soluble checkpoint proteins, plasma EBV-DNA, and cytokines in NPC patients treated with IMRT.Methods.In this study, the plasma samples of 37 NPC patients and 40 healthy controls were collected. Luminex MAGPIX was used to detect the concentrations of 32 plasma targets, including soluble programmed cell death 1 (sPD-1). RT-qPCR was used to measure EBV-DNA.Results.The concentrations of 33 plasma targets were detected in NPC patients before and after IMRT to explore the changes after IMRT. The results showed that IMRT could increase the expression of sPD-1 and significantly reduce the level of EBV-DNA in the plasma of NPC patients. The expression level of sPD-1 in TNM I/II patients was significantly higher than that in III/IV patients. Besides, the concentrations of 12 other targets were significantly different after IMRT, including LAG-3, PD-L1, TIM-3, IFN-γ, IL-12p70, IL-1β, IL-5, IL-6, TNF-α, IL-10, IL-17A, and IL-22. High sPD-1 patients had longer survival than those with low sPD-1. Also, patients with lower EBV-DNA and TNM grades I and II/III had longer survival than those with higher EBV-DNA or TNM IV.Conclusions.This study demonstrated that the concentration of sPD-1 was significantly increased and EBV-DNA was significantly reduced in the NPC patients after IMRT. Plasma EBV-DNA level was a highly specific and sensitive biomarker for NPC diagnosis. Both sPD-1 expression and EBV-DNA concentration in plasma were related to the survival of patients.

Ovarian follicular cysts are anovulatory follicular structures that have been identified in sows and are known to cause infertility. The pathogenesis of follicular cysts remains poorly understood. Hormones play key roles in the formation and persistence of cysts. The hormone inhibin is a member of the TGF-β superfamily and is named for its negative regulation of FSH, another hormone that controls follicular recruitment and growth. In the present study, 48 sows with follicular cysts and 60 normal sows with no cysts were screened for mutations in the inhibin-α gene to examine the association of inhibin-α gene polymorphisms with the presence of follicular cysts. The results show that the c.-42G>A and c.3222G>A polymorphisms are significantly associated with follicular cysts and that sows with c.-42GG and c.3222GG genotypes have lower risk of developing cysts. Our findings may provide novel biological biomarkers and promising gene therapy candidates for follicular cyst formation in sows, which would greatly benefit pig breeding programs.

4-Methylcatechol (4-MC) is one of the metabolites of quercetin, which is a potential drug for neuroprotection and tumorigenesis inhibition. This study was performed to investigate the cytotoxic effect of 4-MC in mouse TM4 Sertoli cells. TM4 Sertoli cell viability was significantly inhibited by 4-MC in a time- and dose-dependent manner. The number of apoptotic and dead cells was significantly increased after 4-MC treatment. Caspase 3 activity increased by prolonged exposure of TM4 Sertoli cells to 200 μM 4-MC. The 4-MC significantly upregulated the mRNA level of Bax gene and considerably downregulated the Bcl-2 gene expression in a concentration-dependent manner. Results showed that 4-MC could induce TM4 Sertoli cell apoptosis, and the cytotoxic effect of 4-MC on TM4 Sertoli cells may be associated with upregulated Bax gene expression, which induced caspase cascade activation.

Background: Remote precoditioning of trauma (RPCT) confers cardioprotective effects against myocardial ischemia/reperfusion injury, which are mediated by spinal opioid receptors. The aim of this study was to identify the roles of opioid receptor subtypes in the cardioprotective effect of RPCT and possible mechanisms. Methods: In this study, 192 Sprague-Dawley rats were allocated to 12 groups. Except for the sham group, rats in all groups were subjected to myocardial ischemia reperfusion. Rats in the ischemia precondition (IPC) group were treated with IPC. In the RPCT groups, an abdominal incision was made 15 min before inducing ischemia. The selective delta-, kappa-, and mu-opioid receptor antagonists were administered to groups of animals receiving RPCT, respectively. Data were collected for myocardial infarct size, intercellular adhesion molecule 1 (ICAM-1), plasma cardiac troponin I (cTnI) concentrations, activation of protein kinase C epsilon (PKCe) in myocardial cell membranes, and adenosine release in the spinal cord. Results: Compared with the control groups, infarct size, plasma concentrations of cTnI, and myocardial ICAM-1 expression were significantly lower, while adenosine release and PKCe activation were enhanced in the IPC and RPCT groups. Compared with the RPCT group, infarct size, plasma cTnI concentration, and myocardial ICAM-1 expression were greater and adenosine release and PKCe activation were reduced in the mu-opioid receptor antagonist plus RPCT group. Conclusions: The spinal mu-opioid receptor mediated the cardiac protective effect of RPCT. The mechanism may be enhanced by adenosine release in the spinal cord and PKCe activation in the myo­cardium, thereby inhibiting inflammation induced by ischemia/reperfusion injury.

Contents Recently, we demonstrated that two members of neurotrophins, nerve growth factor and brain-derived neurotrophic factor, and two types of receptor, tyrosine kinase A (TrkA) and tyrosine kinase (TrkB), exist in ejaculated bull spermatozoa, and play a crucial role in the normal function of spermatozoa. Neurotrophin-4 (NT-4) is another neurotrophic factor that signals predominantly through the TrkB receptor tyrosine kinase, and no reports of detection of NT-4 in spermatozoa have been published. In the present study, the presence of NT-4 in mature bull spermatozoa was investigated using RT-PCR, immunofluorescence and Western blotting. The result shows that there was no RT-PCR evidence for NT-4 transcripts in bovine spermatozoa. However, the NT-4 protein was present in bovine spermatozoa, and the NT-4 immunoreactivity was localized to the equatorial segment and midpiece of bovine spermatozoa. In addition, effects of NT-4 on function of spermatozoa were studied. Significant increased mitochondria activity of mature bovine spermatozoa was observed in response to 300 or 500 ng/ml exogenous NT-4 (p 0.05). Consequently, this study provided evidence that NT-4 protein was presented in the mature bull spermatozoa and can influence the mitochondrial activity of bovine spermatozoa through TrkB tyrosine kinase–dependent pathways.

Ovarian follicular cysts are anovulatory follicular structures that lead to infertility. Hormones play key roles in the formation and persistence of cysts. Inhibins are heterodimeric gonadal glycoprotein hormones that belong to the transforming growth factor-β superfamily. These hormones suppress the secretion of follicle-stimulating hormone. In this report, partial fragment of inhibin-α (INHA) subunit gene of Large White pig was detected from the genomic DNA by polymerase chain reaction. The sequence showed a 283 bp fragment insertion/deletion (I/D) polymorphism in INHA subunit gene. A total of 49 Large White sows with cystic follicles and 152 normal sows were screened for this polymorphism. The relationship of INHA I/D polymorphisms with follicular cysts was investigated. The distribution of I/D was significantly different between cystic and normal sows, thereby suggesting that the INHA subunit gene might be a potential biological marker for breeding programs in pig.

Inhibins play important roles in normal gonadal function, including regulation of proliferation, differentiation, and steroidogenesis of Leydig and Sertoli cells via paracrine and autocrine processes. In adult males, circulating inhibin levels are correlated with fertility by regulating the number of Sertoli cells, total sperm count, and testicular volume. Given this important role, inhibin-α subunit (INHA) is a strong candidate gene in male fertility. However, limited data regarding the association of polymorphisms of INHA with male fertility are available. This study was based on the hypothesis that polymorphisms in the promoter of INHA are associated with male fertility. Han Chinese patients with non-normozoospermia ( n = 153) and normozoospermia ( n = 72) from Northern China were screened, and genotypes were analyzed by polymerase chain reaction–restriction fragment length polymorphism after INHA promoter was amplified. Statistical analysis results revealed a significant difference in the allele frequency of INHA promoter between males with non-normozoospermia and normozoospermia. For c.-124G > A, males carrying c.-124GG genotype and c.-124GA genotype showed an increased risk of non-normozoospermic syndrome. For c.-16C > T polymorphism, no significant difference in allele frequency was observed between the two groups. Therefore, the haplotype AC possibly displayed a considerable reduced risk of non-normozoospermic syndrome.

Nerve growth factor promotes the survival and differentiation of nervous cells and is thought to play an important role in the development of reproductive tissues. The aims of this work were to detect the presence of NGF and its receptor NTRK1 in bovine oviduct samples, and to investigate the regulatory interactions between NGF/NTRK1 and gonadotrophins in bovine oviduct epithelial cells. Both transcripts and proteins of NGF and NTRK1 were detected by RT-PCR and Western blotting, and the corresponding proteins were specifically immunolocalized in oviduct epithelial cells. In addition, real-time PCR experiments revealed that the levels of NGF and NTRK1 mRNA in oviduct epithelial cells treated with exogenous FSH or LH were greater than those in negative control cells (P

The neurotrophin family of proteins promote the survival and differentiation of nerve cells and are thought to play an important role in development of reproductive tissues. The objective of the present study was to detect the presence of Brain-derived neurotrophic factor (BDNF) and its receptor TrkB in bovine sperm, and explore the potential role of BDNF in sperm function. We demonstrated that both the neorotrophin BDNF and the tyrosine kinase receptor protein TrkB were expressed in ejaculated bovine sperm. Furthermore, BDNF per se was secreted by sperm. Insulin and leptin secretion by bovine sperm were increased (P < 0.01) when cells were exposed to exogenous BDNF, whereas insulin was decreased by K252a. Therefore, we inferred that BDNF could be a regulator of sperm secretion of insulin and leptin through the TrkB receptor. Sperm viability and mitochondrial activity were both decreased (P < 0.05) when the BDNF/TrkB signaling pathway was blocked with K252a. Furthermore, BDNF promoted apoptosis of bovine sperm through TrkB binding (P < 0.05). In conclusion, these observations provided evidence that BDNF secreted by bovine sperm was important in regulation of insulin and leptin secretion in ejaculated bovine sperm. Furthermore, BDNF may affect sperm mitochondrial activity and apoptosis, as well as their viability.