Fundamental insights and molecular interactions in pancreatic cancer: Pathways to therapeutic approaches.

The gastrointestinal tract can be affected by a number of diseases that pancreatic cancer (PC) is a malignant manifestation of them. The prognosis of PC patients is unfavorable and because of their diagnosis at advanced stage, the treatment of this tumor is problematic. Owing to low survival rate, there is much interest towards understanding the molecular profile of PC in an attempt in developing more effective therapeutics. The conventional therapeutics for PC include surgery, chemotherapy and radiotherapy as well as emerging immunotherapy. However, PC is still incurable and more effort should be performed. The molecular landscape of PC is an underlying factor involved in increase in progression of tumor cells. In the presence review, the newest advances in understanding the molecular and biological events in PC are discussed. The dysregulation of molecular pathways including AMPK, MAPK, STAT3, Wnt/ß-catenin and non-coding RNA transcripts has been suggested as a factor in development of tumorigenesis in PC. Moreover, cell death mechanisms such as apoptosis, autophagy, ferroptosis and necroptosis demonstrate abnormal levels. The EMT and glycolysis in PC cells enhance to ensure their metastasis and proliferation. Furthermore, such abnormal changes have been used to develop corresponding pharmacological and nanotechnological therapeutics for PC.

Twisted microdomains in liquid crystals for polarization-insensitive phase modulation.

Polarization-independent phase modulators based upon liquid crystals (LCs) with a simple device architecture have long been desired for a range of optical applications. Recently, researchers have demonstrated a novel fabrication procedure using cholesteric LCs as a primer for achieving low polarization dependence coupled with a large phase modulation depth.

Treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs.

Adenocarcinoma is a common type of malignant tumor, originating from glandular epithelial cells in various organs, such as pancreas, breast, lung, stomach, colon, rectus, and prostate. For patients who lose the opportunity for radical surgery, medication is available to provide potential clinical benefits. However, drug resistance is a big obstacle to obtain desired clinical prognosis. In this review, we provide a summary of treatment strategies and drug resistance mechanisms in adenocarcinoma of different organs, including pancreatic cancer, gastric adenocarcinoma, colorectal adenocarcinoma, lung adenocarcinoma, and prostate cancer. Although the underlying molecular mechanisms involved in drug resistance of adenocarcinoma vary from one organ to the other, there are several targets that are universal for drug resistance in adenocarcinoma, and targeting these molecules could potentially reverse drug resistance in the treatment of adenocarcinomas.

Non-selective beta-blockers and the incidence of hepatocellular carcinoma in patients with cirrhosis: a meta-analysis.

Background: Hepatocellular carcinoma (HCC) is a serious complication of cirrhosis. Currently, non-selective beta-blockers (NSBBs) are commonly used to treat portal hypertension in patients with cirrhosis. The latest research shows that NSBBs can induce apoptosis and S-phase arrest in liver cancer cells and inhibit the development of hepatic vascular endothelial cells, which may be effective in preventing HCC in cirrhosis patients. Aim: To determine the relationship between different NSBBs and HCC incidence in patients with cirrhosis. Methods: We searched the Cochrane database, MEDLINE, EMBASE, PubMed, and Web of Science. Cohort studies, case‒control studies, and randomized controlled trials were included if they involved cirrhosis patients who were divided into an experimental group using NSBBs and a control group with any intervention. Based on heterogeneity, we calculated odds ratio (OR) and 95% confidence interval (CI) using random-effect models. We also conducted subgroup analysis to explore the source of heterogeneity. Sensitivity analysis and publication bias detection were performed. Results: A total of 47 studies included 38 reporting HCC incidence, 26 reporting HCC-related mortality, and 39 reporting overall mortality. The HCC incidence between the experimental group and the control group was OR = 0.87 (0.69 and 1.10), p = 0.000, and I2 = 81.8%. There was no significant association between propranolol (OR = 0.94 and 95%CI 0.62-1.44) or timolol (OR = 1.32 and 95%CI 0.44-3.95) and HCC incidence, while the risk of HCC decreased by 26% and 38% with nadolol (OR = 0.74 and 95%CI 0.64-0.86) and carvedilol (OR = 0.62 and 95%CI 0.52-0.74), respectively. Conclusion: Different types of NSBB have different effects on the incidence of patients with cirrhosis of the liver, where nadolol and carvedilol can reduce the risk. Also, the effect of NSBBs may vary in ethnicity. Propranolol can reduce HCC incidence in Europe and America. Systematic Review Registration: identifier https://CRD42023434175, https://www.crd.york.ac.uk/PROSPERO/.

Hypoglycemic agents and incidence of pancreatic cancer in diabetic patients: a meta-analysis.

Background and aims: Hypoglycemic agents are the primary therapeutic approach for the treatment of diabetes and have been postulated to impact pancreatic cancer (PC) incidence in diabetic patients. We conducted a meta-analysis to further evaluate and establish the associations between four common types of hypoglycemic agents [metformin, sulfonylureas, thiazolidinediones (TZDs), and insulin] and PC incidence in individuals with diabetes mellitus (DM). Methods: A comprehensive literature search of PubMed, Web of Science, Embase, and the Cochrane Library identified studies that analyzed the relationship between hypoglycemic agents and PC published between January 2012 and September 2022. Randomized control trials (RCTs), cohorts, and case-control studies were included if there was clear and evaluated defined exposure to the involved hypoglycemic agents and reported PC outcomes in patients with DM. Furthermore, reported relative risks or odds ratios (ORs) or other provided data were required for the calculation of odds ratios. Summary odds ratio estimates with a 95% confidence interval (CI) were estimated using the random-effects model. Additionally, subgroup analysis was performed to figure out the source of heterogeneity. Sensitivity analysis and publication bias detection were also performed. Results: A total of 11 studies were identified that evaluated one or more of the hypoglycemic agents, including three case-control studies and eight cohort studies. Among these, nine focused on metformin, six on sulfonylureas, seven on TZDs, and seven on insulin. Meta-analysis of the 11 observational studies reported no significant association between metformin (OR = 1.04, 95% CI 0.73-1.46) or TZDs (OR = 1.13, 95% CI 0.73-1.75) and PC incidence, while the risk of PC increased by 79% and 185% with sulfonylureas (OR = 1.79, 95% CI 1.29-2.49) and insulin (OR = 2.85, 95% CI 1.75-4.64), respectively. Considerable heterogeneity was observed among the studies and could not be fully accounted for by study design, region, or adjustment for other hypoglycemic agents. Conclusion: Sulfonylureas and insulin may increase the incidence of pancreatic cancer in diabetic patients, with varying effects observed among different ethnicities (Asian and Western). Due to significant heterogeneity across studies, further interpretation of the relationship between hypoglycemic agents and pancreatic cancer incidence in diabetic patients requires well-adjusted data and better-organized clinical trials.

Qualitative and quantitative determination of chemical constituents in Jinbei oral liquid, a modern Chinese medicine for coronavirus disease 2019, by ultra-performance liquid chromatography coupled with mass spectrometry.

Introduction: Traditional Chinese medicine (TCM) has the advantages of syndrome differentiation and rapid determination of etiology, and many TCM prescriptions have been applied to the clinical treatment of coronavirus disease 2019 (COVID-19). Among them, Jinbei Oral Liquid (Jb.L) has also shown an obvious curative effect in the clinic, but the related material basic research is relatively limited. Methods: Therefore, in this process, a systematic data acquisition and mining strategy was established using ultra-high- performance liquid chromatography coupled with quadruple time-of-flight mass spectrometry (UPLC-Q-TOF-MS). Results and Discussion: With the optimized conditions, a total of 118 peaks were tentatively characterized, including 43 flavonoids, 26 phenylpropanoids, 14 glycosides, 9 phthalides, 8 alkaloids and others. To determine the content of relevant pharmacological ingredients, we firstly exploited the ultra-performance liquid chromatography method coupled with triple-quadrupole tandem mass spectrometry (UPLC-QqQ-MS/MS) method for simultaneous detection of 31 active ingredients within 17 min, and the validation of methodology showed that this method has good precision and accuracy. Moreover, analyzing the pharmacology of 31 individual of the medicinal material preliminarily confirmed the efficacy of Jb.L and laid a foundation for an in-depth study of network pharmacology.

The Age-Accompanied and Diet-Associated Remodeling of the Phospholipid, Amino Acid, and SCFA Metabolism of Healthy Centenarians from a Chinese Longevous Region: A Window into Exceptional Longevity.

As centenarians provide a paradigm of healthy aging, investigating the comprehensive metabolic profiles of healthy centenarians is of utmost importance for the pursuit of health and longevity. However, relevant reports, especially studies considering the dietary influence on metabolism, are still limited, mostly lacking the guidance of a model of healthy aging. Therefore, exploring the signatures of the integrative metabolic profiles of the healthy centenarians from a famous longevous region, Bama County, China, should be an effective way. The global metabolome in urine and the short-chain fatty acids (SCFAs) in the feces of 30 healthy centenarians and 31 elderly people aged 60−70 from the longevous region were analyzed by non-targeted metabolomics combined with metabolic target analysis. The results showed that the characteristic metabolites related to longevity were mostly summarized into phosphatidylserine, lyso-phosphatidylethanolamine, phosphatidylcholine, phosphatidylinositol, bile acids, and amino acids (p < 0.05). Six metabolic pathways were found significant relevant to longevity. Furthermore, acetic acid, propionic acid, butyric acid, valeric acid, and total SCFA were significantly increased in the centenarian group (p < 0.05) and were also positively associated with the dietary fiber intake (p < 0.01). It was age-accompanied and diet-associated remodeling of phospholipid, amino acid, and SCFA metabolism that expressed the unique metabolic signatures related to exceptional longevity. This metabolic remodeling is suggestive of cognitive benefits, better antioxidant capacity, the attenuation of local inflammation, and health-span-promoting processes, which play a critical and positive role in shaping healthy aging.

Engineering the microwave to infrared noise photon flux for superconducting quantum systems.

Electromagnetic filtering is essential for the coherent control, operation and readout of superconducting quantum circuits at milliKelvin temperatures. The suppression of spurious modes around transition frequencies of a few GHz is well understood and mainly achieved by on-chip and package considerations. Noise photons of higher frequencies - beyond the pair-breaking energies - cause decoherence and require spectral engineering before reaching the packaged quantum chip. The external wires that pass into the refrigerator and go down to the quantum circuit provide a direct path for these photons. This article contains quantitative analysis and experimental data for the noise photon flux through coaxial, filtered wiring. The attenuation of the coaxial cable at room temperature and the noise photon flux estimates for typical wiring configurations are provided. Compact cryogenic microwave low-pass filters with CR-110 and Esorb-230 absorptive dielectric fillings are presented along with experimental data at room and cryogenic temperatures up to 70 GHz. Filter cut-off frequencies between 1 to 10 GHz are set by the filter length, and the roll-off is material dependent. The relative dielectric permittivity and magnetic permeability for the Esorb-230 material in the pair-breaking frequency range of 75 to 110 GHz are measured, and the filter properties in this frequency range are calculated. The estimated dramatic suppression of the noise photon flux due to the filter proves its usefulness for experiments with superconducting quantum systems.

Generation and characterization of stable pig pregastrulation epiblast stem cell lines.

Pig epiblast-derived pluripotent stem cells are considered to have great potential and broad prospects for human therapeutic model development and livestock breeding. Despite ongoing attempts since the 1990s, no stably defined pig epiblast-derived stem cell line has been established. Here, guided by insights from a large-scale single-cell transcriptome analysis of pig embryos from embryonic day (E) 0 to E14, specifically, the tracing of pluripotency changes during epiblast development, we developed an in vitro culture medium for establishing and maintaining stable pluripotent stem cell lines from pig E10 pregastrulation epiblasts (pgEpiSCs). Enabled by chemical inhibition of WNT-related signaling in combination with growth factors in the FGF/ERK, JAK/STAT3, and Activin/Nodal pathways, pgEpiSCs maintain their pluripotency transcriptome features, similar to those of E10 epiblast cells, and normal karyotypes after more than 240 passages and have the potential to differentiate into three germ layers. Strikingly, ultradeep in situ Hi-C analysis revealed functional impacts of chromatin 3D-spatial associations on the transcriptional regulation of pluripotency marker genes in pgEpiSCs. In practice, we confirmed that pgEpiSCs readily tolerate at least three rounds of successive gene editing and generated cloned gene-edited live piglets. Our findings deliver on the long-anticipated promise of pig pluripotent stem cells and open new avenues for biological research, animal husbandry, and regenerative biomedicine.

Coal and gangue identification method based on the intensity image of lidar and DenseNet.

Coal and gangue (rock) identification is the essential process in a coal preparation plant. In an actual coal preparation plant, the existing classification methods have many disadvantages in safety and identification rate. We utilized the echo intensity image (EII) of lidar for coal and gangue identification for the first time, to the best of our knowledge, and achieved outstanding recognition results with a convolutional neural network. First, we acquire the information of the 3D point cloud, including the distance and the echo intensity, and decompose them into two channels. Then, we utilize the distance channel to remove the background noises and separate the object and the echo intensity channel to construct the 2D EII. Finally, we prune the dense convolutional network (DenseNet-121) to DenseNet-40 for the real-time identification and compare its F1 score with the other two traditional recognition algorithms. The experiment shows that the F1 score of the DenseNet-40 is up to 0.96, which indicates the DenseNet-40 is provably higher than other traditional algorithms in accuracy. Through trial and error, we find that the echo intensity of lidar can clearly show the texture information of coal and gangue. After combining with the DenseNet-40, it has more benefits than the existing classification methods in accuracy, efficiency, and robustness.

Melatonin Restores the Developmental Competence of Heat Stressed Porcine Oocytes, and Alters the Expression of Genes Related to Oocyte Maturation.

Melatonin enhances the quality and in vitro maturation (IVM) of oocytes under heat stress (HS), but the mechanism of melatonin in reducing HS injury on oocytes is not fully understood. In this study, porcine cumulus-oocyte complexes (COCs) were randomly divided into three groups. The COCs of the control group were cultured at 38.5 °C for 42 h, and the COCs of the HS group were cultured at 41.5 °C for 4 h, and then transferred into 38.5 °C for 38 h. The COCs of the HS + melatonin group were cultured with 10-9 M melatonin under the same conditions as the HS group. The survival rate, maturation rate, distribution of α-tubulin and F-actin of the oocytes were assessed. In addition, the expression profiles for genes related to the oocyte maturation, including heat shock protein 70 (HSP70), nuclear factor erythroid 2-related factor 2 (NRF2), cyclin-dependent kinase 1 (CDK1), growth differentiation factor 9 (GDF9) were analyzed by real-time quantitative PCR. The results showed that HS decreased the survival rate and maturation rate, distribution of α-tubulin and F-actin, but melatonin treatment could partly counteract these adverse effects. In addition, HS increased expression of HSP70 and NRF2 mRNA, and melatonin treatment had a similar effect on HSP70 expression, but had a contrary effect on NRF2 expression. Furthermore, HS inhibited expression of CDK1 and GDF9 mRNA, but melatonin treatment could weaken the effect on GDF9 expression induced by HS. In summary, melatonin treatment could attenuate the unfavorable effects induced by HS to enhance developmental competence of porcine oocytes during IVM.

Robotic Label-Free Precise Oocyte Enucleation for Improving Developmental Competence of Cloned Embryos.

OBJECTIVE: The invisibility of domestic oocyte nucleus in bright field currently forces operators to blindly aspirate nucleus out in oocyte enucleation, usually causing large cytoplasm losses and poor developmental competences of cloned embryos. Although fluorescent labeling of nucleus allows for nucleus localization, the involved photobleaching problems and barriers to the execution of enucleation process limit its online-application in oocyte enucleation. This paper reports a novel label-free oocyte enucleation method for precise removal of the nucleus with less cytoplasm loss. METHODS: The relative positions between the injection pipette and nucleus for complete removal of nucleus with less cytoplasm loss were determined through a finite element modeling of nucleus aspiration. To position injection pipette to the above positions relative to nucleus, the appropriate oocyte orientation and trajectory of injection pipette inside oocyte were derived according to the offline-calibrated 3-D distribution of nucleus and the simulated dynamic drift of nucleus that occurs as injection pipette is maneuvered inside oocyte. Finally, a robotic label-free precise enucleation procedure was established. RESULTS: The experimental results on more than 1000 porcine oocytes proved that this system is capable of reducing cytoplasm loss by 60% at the same level of enucleation success rate and almost doubling the cleavage rate of clone embryos in comparison to blind aspiration method. CONCLUSIONS: The results prove that our method significantly improves the developmental competence of cloned embryos in comparison to manual enucleation method. SIGNIFICANCE: Our method is expected to improve the extremely low success rate of animal cloning in the future.

Elevation of MPF and MAPK gene expression, GSH content and mitochondrial distribution quality induced by melatonin promotes porcine oocyte maturation and development in vitro.

The MPF and MAPK genes play crucial roles during oocyte maturation processes. However, the pattern of MPF and MAPK gene expression induced by melatonin (MT) and its correlation to oocyte maturation quality during the process of porcine oocyte maturation in vitro remains unexplored. To unravel it, in this study, we cultured the porcine oocytes in maturation medium supplemented with 0, 10-6, 10-9, and 10-12 mol/L melatonin. Later, we analyzed the MPF and MAPK gene expression levels by RT-PCR and determined the maturation index (survival and maturation rate of oocytes). The GSH content in the single oocyte, and cytoplasmic mitochondrial maturation distribution after porcine oocyte maturation in vitro was also evaluated. We also assessed the effects of these changes on parthenogenetic embryonic developmental potential. The oocytes cultured with 10-9mol/L melatonin concentration showed higher oocyte maturation rate, and MPF and MAPK genes expression levels along with better mitochondrial distribution than the 0, 10-6, and 10-12 mol/L melatonin concentrations (p < 0.05). No significant difference was observed in the survival rates when the oocytes were cultured with different melatonin concentrations. The expression of the MPF gene in the oocytes cultured with 10-6 mol/L melatonin was higher than with 10-12 and 0 mol/L melatonin, and the expression of the MAPK gene in 10-6 and 10-12 group was higher than the control (p < 0.05). As far as the embryonic developmental potential is concerned, the cleavage and blastocyst rate of oocytes cultured with 10-6 and 10-9 mol/L melatonin was significantly higher than the 10-12 mol/L melatonin and control. In conclusion, 10-9-10-6 mol/L melatonin significantly induced the MPF and MAPK gene expression; besides, it could also be correlated with GSH content of single oocyte, mitochondrial maturation distribution, and the first polar body expulsion. These changes were also found to be associated with parthenogenetic embryo developmental potential in vitro.

Changes in expression of interferon-stimulated genes and ubiquitin activating enzyme E1-like in ovine thymus during early pregnancy.

As the main signal for the maternal recognition in ruminants, interferon-tau (IFNT) stimulates expression of interferon-stimulated genes (ISGs) in uterus and many extrauterine tissues. However, it is unclear that early pregnancy induces expression of signal transducer and activator of transcription 1 (STAT1), myxovirusresistance 1 (Mx1), interferon-gamma-inducible protein 10 (IP-10) and ubiquitin activating enzyme E1-like protein (UBE1L) in maternal thymus. In this study, ovine thymuses were sampled on day 16 of the estrous cycle and on days 13, 16 and 25 of gestation, and the expression of STAT1, Mx1, IP-10 and UBE1L was detected by real-time quantitative PCR, Western blot and immunohistochemistry. The results revealed that the expression of STAT1 and IP-10 reached peaks on day 16 of pregnancy, and expression of Mx1 was enhanced on day 25 of pregnancy, and STAT1 protein was located in the epithelial reticular cells, capillaries and thymic corpuscles. However, expression of UBE1L was declined during early pregnancy. In conclusion, early pregnancy influences expression of STAT1, Mx1, IP-10 and UBE1L in maternal thymus, which may participate in regulation of maternal immune tolerance during early pregnancy in sheep.

Effects of early pregnancy on expression of interferon-stimulated gene 15, STAT1, OAS1, MX1, and IP-10 in ovine liver.

Interferon-tau (IFNT) regulates maternal recognition during early pregnancy in ruminants. The liver can serve as a hematopoietic organ, and it has immune functions. This study hypothesized whether mRNA and proteins of interferon-stimulated genes (ISGs) induced by early pregnancy are upregulated in maternal liver. Therefore, we determined the expression of interferon-stimulated gene 15-kDa protein (ISG15), 2',5'-oligoadenylate synthetase 1 (OAS1), myxovirus resistance protein 1 (MX1), interferon-gamma-inducible protein 10 (IP-10), and signal transducer and activator of transcription 1 (STAT1) in maternal livers during early pregnancy in sheep. Ovine livers were sampled on day 16 of the estrous cycle, and days 13, 16, and 25 of pregnancy, and expression of ISGs was detected by quantitative real-time PCR, Western blot, and immunohistochemistry analysis. Our results showed that there were increases in expression of the mRNA and proteins of ISG15, OAS1, IP-10, STAT1, and MX1 during early pregnancy. STAT1 protein was limited to the hepatocytes, and endothelial cells of proper hepatic arteries and hepatic portal veins. In conclusion, the upregulation of ISG15, OAS1, IP-10, STAT1, and MX1 proteins may be implicated in maternal hepatic immune adjustment and other functions during early pregnancy in sheep.

Expression of melatonin receptors and CD4 in the ovine thymus, lymph node, spleen and liver during early pregnancy.

As a pineal gland hormone, melatonin acts through its receptors to modulate the immune system. The immune system is composed of primary and secondary organs, and immune organs are adapted to the presence of the fetal alloantigen during pregnancy. However, it is unclear whether melatonin affects maternal immune organs during early pregnancy in sheep. In this study, the ovine thymus, lymph node, spleen and liver were sampled at day 16 of the oestrous cycle, and at days 13, 16 and 25 of pregnancy. The expression of melatonin receptor 1A (MT1), melatonin receptor 1B (MT2) and cluster of differentiation 4 (CD4) was detected by quantitative real-time polymerase chain reaction, Western blot and immunohistochemistry experiments. Our results showed that during early pregnancy there was an upregulation of MT1 mRNA and protein in the thymus, lymph node and liver, and there was a downregulation in the spleen. The expression of MT2 mRNA and protein was increased in the thymus but decreased in the spleen and liver, and there was no significant change in the lymph node during early pregnancy. CD4 protein was upregulated in the thymus, lymph node and liver, but there were no significant changes in the spleen during early pregnancy. In conclusion, early pregnancy induces tissue-specific expression of MT1, MT2 and CD4, which may be due to the different functions of the thymus, lymph node, spleen and liver. Further, melatonin is involved in immune regulation of the maternal thymus, lymph node, spleen and liver during early pregnancy in sheep.

Effect of Melatonin on the In Vitro Maturation of Porcine Oocytes, Development of Parthenogenetically Activated Embryos, and Expression of Genes Related to the Oocyte Developmental Capability.

Melatonin treatment can improve quality and in vitro development of porcine oocytes, but the mechanism of improving quality and developmental competence is not fully understood. In this study, porcine cumulus-oocyte complexes were cultured in TCM199 medium with non-treated (control), 10-5 M luzindole (melatonin receptor antagonist), 10-5 M melatonin, and melatonin + luzindole during in vitro maturation, and parthenogenetically activated (PA) embryos were treated with nothing (control), or 10-5 M melatonin. Cumulus oophorus expansion, oocyte survival rate, first polar body extrusion rate, mitochondrial distribution, and intracellular levels of reactive oxygen species (ROS) and glutathione of oocytes, and cleavage rate and blastocyst rate of the PA embryos were assessed. In addition, expression of growth differentiation factor 9 (GDF9), tumor protein p53 (P53), BCL2 associated X protein (BAX), catalase (CAT), and bone morphogenetic protein 15 (BMP15) were analyzed by real-time quantitative PCR. The results revealed that melatonin treatment not only improved the first polar body extrusion rate and cumulus expansion of oocytes via melatonin receptors, but also enhanced the rates of cleavage and blastocyst formation of PA embryos. Additionally, melatonin treatment significantly increased intraooplasmic level of glutathione independently of melatonin receptors. Furthermore, melatonin supplementation not only significantly enhanced mitochondrial distribution and relative abundances of BMP15 and CAT mRNA, but also decreased intracellular level of ROS and relative abundances of P53 and BAX mRNA of the oocytes. In conclusion, melatonin enhanced the quality and in vitro development of porcine oocytes, which may be related to antioxidant and anti-apoptotic mechanisms.

Modulation of Helper T Cytokines in Thymus during Early Pregnancy in Ewes.

There is an immune tolerance in maternal immune system during pregnancy, and thymus is a main organ of the immune system. Helper T (Th)1 and Th2 cytokines are involved in the regulation of immune system, but the modulation of Th cytokines in the thymus during early pregnancy is unclear in ewes. Thymuses were collected on day 16 of the estrous cycle, and on days 13, 16, and 25 of pregnancy in ewes. qRT-PCR, Western blot, and immunohistochemistry were used to analyze the expression of Th1 and Th2 cytokines in the thymuses. There was a peak in the expression of interferon-gamma (IFN-γ) on day 16 of pregnancy, an upregulation of tumor necrosis factor beta (TNF-ß), and a sustained expression of interleukin-2 (IL-2) and IL-4. Furthermore, there was a peak in the expression of IL-6 on day 13 of pregnancy, no expression of IL-6 on day 16 of the estrous cycle and day 25 of pregnancy, and an upregulation of IL-5 and IL-10 in the thymuses during early pregnancy. The immunohistochemistry results revealed that the IFN-γ and IL-6 proteins were limited to the stromal cells, capillaries, and thymic corpuscles. In conclusion, early pregnancy influenced the production of Th1 and Th2 cytokines of maternal thymus in sheep.

Differential expression of T helper cytokines in the liver during early pregnancy in sheep.

Liver plays important roles in the innate and adaptive immunity, and contributes to the maternal immune adjustments during pregnancy in mice and rats. T helper 1 (Th1) and Th2 cytokines are related to immune response. However, expression of Th1 and Th2 cytokines in maternal livers is unclear during early pregnancy in sheep. In this study, livers were collected on day 16 of the estrous cycle and on days 13, 16 and 25 of pregnancy (n = 6 for each group) in ewes, and qRT-PCR, western blot and immunohistochemistry were used to analyze the expression of Th1 and Th2 cytokines in the livers. Our results showed that interferon-gamma (IFN-γ), interleukin (IL)-2, IL-4, IL-6 and IL-10 were downregulated, and IL-5 was upregulated in the livers during early pregnancy. Furthermore, there was no effect for early pregnancy on expression of TNF-ß in the livers, and the IFN-γ protein was limited to the endothelial cells of the proper hepatic arteries and portal veins. In conclusion, early pregnancy exerted its effect on the liver to regulate the Th cytokines expression, but there was no evident shift from Th1 to Th2 cytokines, which may be necessary for the maternal hepatic immune adjustments during early pregnancy in sheep.