Zinc alleviates thermal stress-induced damage to the integrity and barrier function of cultured chicken embryonic primary jejunal epithelial cells via the MAPK and PI3K/AKT/mTOR signaling pathways.

Zinc (Zn) could alleviate the adverse effect of high temperature (HT) on intestinal integrity and barrier function of broilers, but the underlying mechanisms remain unclear. We aimed to investigate the possible protective mechanisms of Zn on primary cultured broiler jejunal epithelial cells exposed to thermal stress (TS). In Exp.1, jejunal epithelial cells were exposed to 40℃ (normal temperature, NT) and 44℃ (HT) for 1, 2, 4, 6, or 8 h. Cells incubated for 8 h had the lowest transepithelial resistance (TEER) and the highest phenol red permeability under HT. In Exp.2, the cells were preincubated with different Zn sources (Zn sulfate as iZn and Zn proteinate with the moderate chelation strength as oZn) and Zn supplemental levels (50 and 100 µmol/L) under NT for 24 h, and then continuously incubated under HT for another 8 h. TS increased phenol red permeability, lactate dehydrogenase (LDH) activity and p-PKC/PKC level, and decreased TEER, cell proliferation, mRNA levels of claudin-1, occludin, zona occludens-1 (ZO-1), PI3K, AKT and mTOR, protein levels of claudin-1, ZO-1 and junctional adhesion molecule-A (JAM-A), and the levels of p-ERK/ERK, p-PI3K/PI3K and p-AKT/AKT. Under HT, oZn was more effective than iZn in increasing TEER, occludin, ZO-1, PI3K, and AKT mRNA levels, ZO-1 protein level, and p-AKT/AKT level; supplementation with 50 µmol Zn/L was more effective than 100 µmol Zn/L in increasing cell proliferation, JAM-A, PI3K, AKT, and PKC mRNA levels, JAM-A protein level, and the levels of p-ERK/ERK and p-PI3K/PI3K; furthermore, supplementation with 50 µmol Zn/L as oZn had the lowest LDH activity, and the highest ERK, JNK-1, and mTOR mRNA levels. Therefore, supplemental Zn, especially 50 µmol Zn/L as oZn, could alleviate the TS-induced integrity and barrier function damage of broiler jejunal epithelial cells possibly by promoting cell proliferation and tight junction protein expression via the MAPK and PI3K/AKT/mTOR signaling pathways.

A meta-analysis of risk factors for a Dacron-cuffed catheter related infection in hemodialysis.

OBJECTIVE: To provide theoretical basis for prevention of a Dacron-cuffed catheter related infection (CRI), the risk factors of CRI in hemodialysis patients were systematically evaluated. METHODS: Eight databases, including PubMed, Cochrane library, EMBASE, Web of Science, China National Knowledge Infrastructure (CNKI), Chinese Biomedical Database (CBM), Wanfang Database and Chinese Scientific Journal Database (VIP), were searched to screen out literatures related to the risk factors of long-term indwelling a Dacron-cuffed CRI in hemodialysis. Meta-analysis of risk factors for a Dacron-cuffed CRI in hemodialysis and publication bias test were performed using RevMan 5.4 software. RESULTS: After screening, 13 literatures involving a Dacron-cuffed CRI were included, with a total of 625 patients, and the infection rate was 11.7%. The combined OR value and 95% confidence interval (CI) of all factors were: Combined with Diabetes (1.94, 1.51 ~ 2.50), Hb (1.82, 1.35 ~ 2.44), age (2.38, 1.06 ~ 5.34), catheter indwelling time (1.79, 1.21 ~ 2.66), serum albumin (2.26, 1.25 ~ 4.08), catheter indwelling site (3.29, 1.74 ~ 6.23) and the number of tube placement (5.40, 2.65 ~ 11.02). CONCLUSIONS: The main risk factors for a Dacron-cuffed CRI in hemodialysis were combined with diabetes, hemoglobin level, age, catheter indwelling time, serum albumin level, femoral vein catheter indwelling and catheterization times. In other words, hemodialysis patients are at higher risk of CRI if they have diabetes, or if they have a lower hemoglobin level, or if they are older, or if they have a longer duration of catheterization, or if they have a lower serum albumin level, or if they have a femoral vein catheter, or if they have more catheters.

PYCR1 regulates TRAIL­resistance in non­small cell lung cancer cells by regulating the redistribution of death receptors.

Although recombinant human TNF-related apoptosis-inducing ligand (TRAIL) protein exhibits antitumor activity in a number of lung and liver cancer cells and tumor-bearing animals, TRAIL resistance has substantially restricted its clinical application. Pyrroline-5-carboxylate reductase 1 (PYCR1) is a key enzyme in the regulation of proline synthesis. PYCR1 is highly expressed in various types of malignant tumor, in which it has been implicated in 5-fluorouracil resistance. However, the possible relationship between PYCR1 and TRAIL resistance remains unclear. In the present study, both reverse transcription-quantitative PCR and western blotting were performed. The results indicated that H1299 cells had higher PYCR1 expression levels and were less sensitive to TRAIL compared with the TRAIL-sensitive cell line, H460. PYCR1 knockdown in H1299 cells increased TRAIL sensitivity, increased the localization of death receptors (DRs) on the cell surface and activated Caspase-3/8. By contrast, overexpression of PYCR1 in H1299 cells decreased TRAIL sensitivity, reduced the distribution of DRs on the cell surface and suppressed the activation of Caspase-3/8. Taken together, these results suggested that PYCR1 promoted TRAIL resistance in the non-small cell lung cancer cell line, H1299, by preventing redistribution of DRs to the plasma membrane. This in turn inhibited TRAIL-mediated cell apoptosis by reducing the activation of Caspase-3/8.

Gene delivery to breast cancer by incorporated EpCAM targeted DARPins into AAV2.

OBJECTIVE: The aim of this study is to evaluate an AAV vector that can selectively target breast cancer cells and to investigate its specificity and anti-tumor effects on breast cancer cells both in vitro and in vivo, offering a new therapeutic approach for the treatment of EpCAM-positive breast cancer. METHODS: In this study, a modified AAV2 viral vector was used, in which EpCAM-specific DARPin EC1 was fused to the VP2 protein of AAV2, creating a viral vector that can target breast cancer cells. The targeting ability and anti-tumor effects of this viral vector were evaluated through in vitro and in vivo experiments. RESULTS: The experimental results showed that the AAV2MEC1 virus could specifically infect EpCAM-positive breast cancer cells and accurately deliver the suicide gene HSV-TK to tumor tissue in mice, significantly inhibiting tumor growth. Compared to the traditional AAV2 viral vector, the AAV2MEC1 virus exhibited reduced accumulation in liver tissue and had no impact on tumor growth. CONCLUSION: This study demonstrates that AAV2MEC1 is a gene delivery vector capable of targeting breast cancer cells and achieving selective targeting in mice. The findings offer a potential gene delivery system and strategies for gene therapy targeting EpCAM-positive breast cancer and other tumor types.

Glutamate secretion by embryonic stem cells as an autocrine signal to promote proliferation.

Glutamate, the major excitatory neurotransmitter in the central nervous system, has also been found to play a role in embryonic stem (ES) cells. However, the exact mechanism and function of glutamatergic signaling in ES cells remain poorly understood. In this study, we identified a glutamatergic transmission circuit in ES cells that operates through an autocrine mechanism and regulates cell proliferation. We performed biological analyses to identify the key components involved in glutamate biosynthesis, packaging for secretion, reaction, and reuptake in ES cells, including glutaminase, vesicular glutamate transporter, glutamate N-methyl-D-aspartate (NMDA) receptor, and cell membrane excitatory amino-acid transporter (EAAT). We directly quantified the released glutamate signal using microdialysis-high performance liquid chromatography-tandem mass spectrometry (MD-HPLC-MS-MS). Pharmacological inhibition of endogenous glutamate release and the resulting tonic activation of NMDA receptors significantly affected ES cell proliferation, suggesting that ES cells establish a glutamatergic autocrine niche via releasing and responding to the transmitter for their own regulation.

Rehmannioside A Inhibits TRAF6/MAPK Pathway and Improves Psoriasis by Interfering with the Interaction of HaCaT Cells with IL-17A.

Objective: As a common chronic inflammatory skin disease, psoriasis seriously affects the physical health and psychological well-being of patients. Various clinical treatments for psoriasis have their own drawbacks, so it is important to find effective and safe drugs. Rehmannioside A (ReA) has anti-inflammatory properties and is the main active ingredient in Fuzhengzhiyanghefuzhiyang decoction (FZHFZY), an herbal compound for the treatment of psoriasis. But no studies have been conducted to determine whether ReA alone can treat psoriasis. Therefore, this study was designed to investigate the effect of ReA in the treatment of psoriasis and its potential mechanism of action. Methods: HaCaT cells were treated with ReA and IL-17A alone for 24 h and 48 h, and the most effective concentrations of ReA and interleukin (IL)-17A were found at 25 µg/mL and 100 ng/mL, respectively. A psoriasis cell model was constructed by stimulating HaCaT cells with IL-17A, followed by intervention with ReA. Cell viability and cell cycle distribution were measured by MTT assay and flow cytometry. The expression levels of keratin family members and chemokines were detected by real-time quantitative PCR (RT-qPCR), the levels of pro-inflammatory cytokines by enzyme-linked immunosorbent assay (ELISA), and key proteins of TRAF6/MAPK signaling pathway by Western blot. Results: ReA weaken cell viability, down-regulate the expression of keratin family members (KRT6 and KRT17), restore cell cycle distribution to normal distribution, inhibit the release of pro-inflammatory cytokines (IL-6, IL-8 and IL-1ß) and lower the expression of chemokines (S100A7, S100A9 and CXCL2) by interfering with the interaction between HaCaT cells and IL-17A. Thus, it exerts an anti-psoriatic effect by reducing the inflammatory response and inhibiting abnormal proliferation of HaCaT cells. Mechanistically, ReA inhibited the TRAF6/MAPK signaling pathway activated by IL-17A stimulation in HaCaT cells. Conclusion: ReA has in vitro anti-psoriatic effects and may be a new therapeutic agent for psoriasis.

Multiple Bound State Soliton Pulses in the All Polarization Maintaining Fiber Laser.

The bound state soliton pulse, a novel mode-locked output state of fiber lasers, has been studied extensively to gain a better understanding of soliton interactions and to explain the mechanism behind the generation of mode-locked pulses. In this particular research, we utilized a self-made saturable absorber (SA) consisting of single-walled carbon nanotubes (SWCNT) in a fully polarization maintaining (PM) erbium-doped fiber optical path. Through this setup, we observed various bound state pulse phenomena, including the double bound state with different phase differences, the bound state formed by two double pulse bound states, the multi-pulse bound state, etc. The abundant bound soliton pulse states demonstrated the excellent nonlinear absorption characteristics of the SA as well as the excellent optical properties of the all-PM fiber laser. It contributed to exploring the relationship between sub pulses and mode-locked pulses in the future. Additionally, due to the strong interaction between bound state solitons and the inherent stability of the PM optical path, there was potential for utilizing this setup as a seed source to enhance the stability of high-power fiber lasers.

Identifying altered developmental pathways in human globoid cell leukodystrophy iPSCs-derived NSCs using transcriptome profiling.

BACKGROUND: Globoid cell leukodystrophy (GLD) is a devastating neurodegenerative disease characterized by widespread demyelination caused by galactocerebrosidase defects. Changes in GLD pathogenesis occurring at the molecular level have been poorly studied in human-derived neural cells. Patient-derived induced pluripotent stem cells (iPSCs) are a novel disease model for studying disease mechanisms and allow the generation of patient-derived neuronal cells in a dish. RESULTS: In this study, we identified gene-expression changes in iPSCs and iPSC-derived neural stem cells (NSCs) from a patient with GLD (K-iPSCs/NSCs) and normal control (AF-iPSCs/NSCs), in order to investigate the potential mechanism underlying GLD pathogenesis. We identified 194 (K-iPSCs vs. AF-iPSCs) and 702 (K-NSCs vs. AF-NSCs) significantly dysregulated mRNAs when comparing the indicated groups. We also identified dozens of Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway terms that were enriched for the differentially expressed genes. Among them, 25 differentially expressed genes identified by RNA-sequencing analysis were validated using real-time quantitative polymerase chain reaction analysis. Dozens of pathways involved in neuroactive ligand-receptor interactions, synaptic vesicle cycle signaling, serotonergic synapse signaling, phosphatidylinositol-protein kinase B signaling, and cyclic AMP signaling were identified as potential contributors to GLD pathogenesis. CONCLUSIONS: Our results correspond to the fact that mutations in the galactosylceramidase gene may disrupt the identified signaling pathways during neural development, suggesting that alterations in signaling pathways contribute to GLD pathogenesis. At the same time, our results demonstrates that the model based on K-iPSCs is a novel tool that can be used to study the underlying molecular basis of GLD.

rAAV2-Mediated Restoration of GALC in Neural Stem Cells from Krabbe Patient-Derived iPSCs.

Krabbe disease is a rare neurodegenerative fatal disease. It is caused by deficiency of the lysosomal enzyme galactocerebrosidase (GALC), which results in progressive accumulation of galactolipid substrates in myelin-forming cells. However, there is still a lack of appropriate neural models and effective approaches for Krabbe disease. We generated induced pluripotent stem cells (iPSCs) from a Krabbe patient previously. Here, Krabbe patient-derived neural stem cells (K-NSCs) were induced from these iPSCs. By using nine kinds of recombinant adeno-associated virus (rAAV) vectors to infect K-NSCs, we found that the rAAV2 vector has high transduction efficiency for K-NSCs. Most importantly, rAAV2-GALC rescued GALC enzymatic activity in K-NSCs. Our findings not only establish a novel patient NSC model for Krabbe disease, but also firstly indicate the potential of rAAV2-mediated gene therapy for this devastating disease.

Generation and characterization of iPS cell line (CTGUi001-A) from skin fibroblasts of a patient with Fabry disease.

We have generated an iPSCs line (CTGUi001-A) from dermal fibroblasts of a 16-year-old male Fabry disease patient with a novel GLA gene mutation (c.156C > A) using Sendai virus encoding the four Yamanaka factors OCT4, SOX2, KLF4, and c-MYC. The CTGUi001-A iPSC line displayed typical embryonic stem cell-like morphology, carried the GLA gene mutation, expressed several pluripotent stem cell makers, retained normal karyotype (46, XY) and was capable of forming teratomas containing three germ layers.

A Rare Case of Breast fat-Forming Solitary Fibrous Tumor With Molecular Confirmation.

Solitary fibrous tumor (SFT) is an uncommon fibroblastic neoplasm which may arise in a wide range of anatomic location and can occur across all ages. Fat-forming SFT is a rare morphological variant of SFT. Primary breast fat-forming SFT is exquisitely rare. Here, we report a case in a 51-year-old Chinese woman with a palpable painless mass in the left breast. A color Doppler ultrasound scan examination demonstrated a 3.4-cm oval, well-circumscribed, hypoechoic solid mass with several peripheral and internal color flow signals. Magnetic resonance imaging (MRI) showed a focal lobulated solid nodular lesion displaying geographical enhancement but no architectural distortion. Subsequently, she underwent a left breast lumpectomy. In histopathologic examination, there was a well-circumscribed, cellular spindle cell tumor consisting of short fascicles of bland, fusiform, ovoid to spindle cells disposed in a patternless architecture around branching vascular spaces within a fibrous stroma with wispy collagen. Cells revealed mild nuclear atypia. Mitotic figures were up to 4/10 high-power fields (HPFs) in the hot spot. Mature adipocytes intermixed with spindle cells were also observed. The tumor cells were diffusely positive for CD34 and STAT6. Some S100-expressing adipocytes co-expressed STAT6. Next-generation sequencing (NGS) revealed the presence of the NAB2exon6::STAT6exon2 fusion. The histological, immunohistochemical (IHC) and molecular examinations confirmed the diagnosis of fat-forming SFT. Post-excision, the patient showed no signs of tumor recurrence or metastasis in a 7-month follow-up. Here, we describe a rare case of a fat-forming SFT involving the breast and highlight the comprehensive pathological evaluation and necessary ancillary testing.

Extracellular matrix physical properties govern the diffusion of nanoparticles in tumor microenvironment.

Nanoparticles (NPs) are confronted with limited and disappointing delivery efficiency in tumors clinically. The tumor extracellular matrix (ECM), whose physical traits have recently been recognized as new hallmarks of cancer, forms a main steric obstacle for NP diffusion, yet the role of tumor ECM physical traits in NP diffusion remains largely unexplored. Here, we characterized the physical properties of clinical gastric tumor samples and observed limited distribution of NPs in decellularized tumor tissues. We also performed molecular dynamics simulations and in vitro hydrogel experiments through single-particle tracking to investigate the diffusion mechanism of NPs and understand the influence of tumor ECM physical properties on NP diffusion both individually and collectively. Furthermore, we developed an estimation matrix model with evaluation scores of NP diffusion efficiency through comprehensive analyses of the data. Thus, beyond finding that loose and soft ECM with aligned structure contribute to efficient diffusion, we now have a systemic model to predict NP diffusion efficiency based on ECM physical traits and provide critical guidance for personalized tumor diagnosis and treatment.

Danlu tongdu tablets: Preclinical safety evaluation and mechanism of hepatotoxicity.

Danlu tongdu tablets (DLTD) is a listed Chinese patent medicine collected in the Pharmacopoeia of the People's Republic of China (version 2020). This prescription has been applied in clinics in China for lumbar spinal stenosis and lumbosacral disc herniations. The wide application of Danlu tongdu in therapy has raised some clinical adverse reactions, such as significant elevation of alanine transaminase (ALT) and aspartate transaminase (AST) in individual patients after use. The present study aimed to investigate the safety of Danlu tongdu and analyze its adverse effects on the liver. The maximum feasible dose (MFD) was used to carry out the acute toxicity tests. Mortality, adverse effects, body weight and food consumption were recorded for up to 14 days post treatment. In the 6-month chronic toxicity test, sprague-dawley rats were randomly divided into four groups according body weight, the experimental groups were administrated to rats at the concentrations of 1.67, 3.34 and 6.67 g/kg/day, whereas the control group was received the ultrapure water (vehicle) only, 10 ml/kg, once a day. The animal's body weight, food consumption was monitored weekly. In addition, their hematological and biochemical parameters, body and organ weights and histopathology, were all measured at specific observation time points. Additionally, we further explored the adverse effects mechanism of Danlu tongdu on the liver through transcriptome analysis. No deaths or substance-relative toxicity were observed in the acute toxicity study or the 6-month chronic toxicity study with doses of 1.67 g/kg and 3.34 g/kg, respectively. We found that mild hypertrophy and hyperplasia of hepatic interlobular bile ducts were detected in some rats with doses of 6.67 g/kg after repeated oral administration of Danlu tongdu for 13 and 26 weeks, but the above changes in liver were reversible. The results of transcriptome sequencing showed that Danlu tongdu had a significant effect on cytochrome P450 enzymes in rat liver, especially cytochrome P450 1 (CYP1) subtype. Therefore, the toxic target organ of Danlu tongdu is the liver and the mechanism of mild liver injury is closely related to the up-regulation of cytochrome P450 1A1 (CYP1A1) and cytochrome P450 1A2 (CYP1A2) expression.

Production and characterization of human induced pluripotent stem cell line (PUMCi002-A) from a Krabbe patient related control to study disease mechanisms associated with GALC mutation.

A KD-control human induced pluripotent stem cells (iPSCs) line (PUMCi002-A) was generated from dermal fibroblasts of a Krabbe patient's father with a c.461C>A mutation in Galactocerebrosidase (GALC) gene. The pluripotency, in vitro differentiation potential and karyotype stability of generated iPSC line were analyzed and confirmed. This cell line can be exploited as a control iPSC line to better understand the mechanisms involved in GALC-associated Krabbe disease and provide plausible new therapeutic directions.

[Effects of a novel spermine oxidase inhibitor SI-4650 on proliferation and EMT of human ovarian cancer SKVO-3 cells].

Objective: To investigate the effects of SI-4650, a novel small molecule inhibitor of spermine oxidase (SMO), on the proliferation and epithelial mesenchymal transformation (EMT) of human ovarian cancer SKVO-3 cells as well as its underlying molecular mechanisms. Methods: SKVO-3 cells treated with 0 µmol/L SI-4650 were used as control group, SKVO-3 cells treated with 30, 60 µmol/L SI-4650 were used as experimental group. The effects of SI-4650 on the activity of SMO, the polyamine contents and the cellular reactive oxygen species (ROS) were detected. Cell proliferation, cell cycle and mitochondrial membrane potential change of SKVO-3 cells were tested. The effects of SI-4650 on apoptosis, migration and invasion were investigated. The effects of SI-4650 on Bax, Bcl-2, Caspase3, E-cadherin, N-cadherin, Vimentin, matrix metalloproteinase 2 ( MMP2) and MMP 9 expression levels in SKVO-3 cells were detected. Results: Comparison between blank control group and experimental groups,SI-4650 could improve the content of SI-4650 in SKVO-3 cells. SI-4650 could inhibit the activity of SMO (P＜0.01), reduce the ROS (P＜0.01)and polyamine content in SKVO-3 cells (P＜0.01). Treatment of SKVO-3 cells with SI-4650 inhibited the proliferation (the inhibition rate was 32.27% and 47.31% in experimental groups), caused S-phase cell cycle arrest (P＜0.01) and induced apoptosis (P＜0.01). The expressions of Bax and c-Caspase3 in SKVO-3 cells were increased (P＜0.01),the content of Bcl-2 was decreased (P＜0.01), and the mitochondrial membrane potential was decreased (P＜0.01), and the number of apoptotic cells was increased(31.41% and 43.51% in experimental groups). At the same time, SI-4650 could change the expression levels of EMT-related factors, increased the expression level of E-cad , decreased the expression levels of N-cad, Vimentin, MMP-2 and MMP-9, and inhibited the migration and invasion of SKVO-3 cells. Conclusion: SI-4650 can effectively inhibit proliferation, invasion and metastasis of human ovarian cancer SKVO-3 cells, and the mechanism may be related to its ability to depress the activity of SMO, interfere polyamine metabolism and induce cell cycle arrest, mitochondrial apoptosis and inhibit EMT. This study reveals potential application of SI-4650 in the treatment of ovarian cancer.

The Role of Kallikrein 7 in Tumorigenesis.

Kallikrein 7 (KLK7) is a secreted serine protease with chymotrypsic protease activity. Abnormally high expression of KLK7 is closely related to the occurrence and development of various types of cancer. Therefore, KLK7 has been identified as a potential target for cancer drug development design in recent years. KLK7 mediates various biological and pathological processes in tumorigenesis, including cell proliferation, migration, invasion, angiogenesis, and cell metabolism, by hydrolyzing a series of substrates such as membrane proteins, extracellular matrix proteins, and cytokines. This review mainly introduces the downstream cell signaling pathways involved in the activation of KLK7 and its substrate-related proteins. This review will not only help us to better understand the mechanisms of KLK7 in regulating biological and pathological processes of cancer cells but also lay a solid foundation for the design of inhibitors targeting KLK7.

Immunological profile of erythema nodosum and their relationship of C-reactive protein level and erythrocyte sedimentation rate: A retrospective analysis of 61 patients.

This experiment was carried out to investigate changes in lymphocyte subpopulation, immunoglobulins (Igs), and complements, and also to explore the relationship between these immune indices and C-reactive protein and erythrocyte sedimentation rate in 61 patients with erythema nodosum. For this aim, a 4-year, retrospective study contained 61 patients with erythema nodosum, and 61 healthy control subjects were included from the out-patient clinic. The subpopulation of the T, B and natural killer lymphocytes and levels of IgA, IgG, IgM, complement C3, complement C4, C-reactive protein, and erythrocyte sedimentation rate from peripheral blood of them were detected. A correlation analysis was done between lymphocyte subpopulation, levels of IgA, IgG, and IgM, complement C3, complement C4 and C-reactive protein level and erythrocyte sedimentation rate in the patient group. Results showed that the percentage of CD4+ cells, CD4+/CD8+ ratio, the level of C-reactive protein and the erythrocyte sedimentation rate in the patients were higher than in controls (P<0.05). While the percentage of CD8+ cells and the serum levels of complement C3 were lower than in controls (P<0.05). There were no differences in the percentages of CD3+, B and natural killer cells and the serum levels of IgA, IgG and IgM, and complement C4 between the patients and the controls (P>0.05). IgM level was positively correlated with C-reactive protein (P<0.05) but did not correlate with an erythrocyte sedimentation rate (P>0.05). There was no correlation between lymphocyte subpopulation, levels of IgA, IgG, complement C3, complement C4 and C-reactive protein level and erythrocyte sedimentation rate (P>0.05). In conclusion, there was dysregulation of both cellular immunity and humoral immunity in patients with erythema nodosum. IgM level has a positive correlation with C-reactive protein.

Overexpression of Mtr-miR319a Contributes to Leaf Curl and Salt Stress Adaptation in Arabidopsis thaliana and Medicago truncatula.

Salt stress is a worldwide agronomic issue that limits crop yield and quality. Improving salt stress tolerance via genetic modification is the most efficient method to conquer soil salinization problems in crops. Crop miRNAs have been declared to be tightly associated with responding and adapting to salt stress and are advantageous for salt tolerance modification. However, very few studies have validated vital salt tolerance miRNAs and coupled potent target genes in Medicago species, the most economically important forage legume species. In this study, Mtr-miR319a, a miRNA that was identified from the previous next-generation sequencing assay of salt-treated Medicago truncatula, was overexpressed in M. truncatula and Arabidopsis thaliana, inducing the curly leaves and salt stress tolerance phenotypes. Combining the elevated expression level of Mtr-miR319a in the M. truncatula overexpression lines under normal and salt-treatment conditions, the regulatory roles of Mtr-miR319a in leaf development and salt stress adaptation were demonstrated. Several predicted target genes of Mtr-miR319a were also regulated by Mtr-miR319a and were associated with the aforementioned phenotypes in M. truncatula plants, most notably MtTCP4. Our study clarified the functional role of Mtr-miR319a and its target genes in regulating leaf development and defending salt stress, which can help to inform crop breeding efforts for improving salt tolerance via genetic engineering.

Red ginseng extract improves skeletal muscle energy metabolism and mitochondrial function in chronic fatigue mice.

Background: Skeletal muscles are organs with high energy requirements, especially during vigorous exercise. Adequate mitochondrial function is essential to meet the high energy needs of skeletal muscle cells. Recent studies have reported that red ginseng can significantly improve chronic fatigue; however, the specific mechanism of action is still not clear. Methods: A chronic fatigue syndrome mouse model was developed using C57BL/6J mice through long-term compound stimulation of stress factors. Following this, the animals were orally administered 200, 400, or 600 mg/kg red ginseng extracts for 28 days. Skeletal muscle lactate acid, serum lactate dehydrogenase, urea concentrations, ATP level, mitochondrial membrane potential, activities of Na+-K+-ATPase and cytochrome c oxidase were determined using assay kits or an automatic biochemical analyser detection system. Skeletal muscle mitochondria morphology was observed using electron microscopy and the expression of p-AMPK, PGC-1α, ACO2 and complex I in skeletal muscle protein was determined by western blotting. Results: Oral administration of 400 or 600 mg/kg red ginseng extract in mice with chronic fatigue reduced lactic acid, lactate dehydrogenase and urea, rescued the density and morphology of skeletal muscle mitochondria, increased the activities of Na+-K+-ATPase and cytochrome c oxidase, and activated the AMPK/PGC-1α cascade pathway, resulting in improved skeletal muscle mitochondrial function by restoring ATP level, mitochondrial membrane potential, complex I and mitochondrial biogenesis. Conclusion: The anti-fatigue effects of red ginseng are partly related to its potent mitochondrial improving activity, including decreasing mitochondrial swelling and mitochondrial membrane permeability, increasing mitochondrial biogenesis, thus ameliorating mitochondrial dysfunction.

Lycopene improves maternal reproductive performance by modulating milk composition and placental antioxidative and immune status.

Placental health and milk quality are important for maternal reproductive performance during pregnancy and lactation. Lycopene plays an important role in antioxidation, anti-inflammation and regulating lipid metabolism. The goal of the present study was to investigate the effects of dietary lycopene supplementation in the pig model on reproductive performance, placental health and milk composition during maternal gestation and lactation. In the present study, the litter size of live piglets was increased and the litter size of dead piglets was decreased by lycopene supplementation of the diet of sows. The litter weight at birth and weaning were increased in the lycopene group. Through placental proteomics, we enriched differentially expressed proteins (DEPs), gene ontology (GO) terms, and Kyoto encyclopedia of proteins and genomes (KEGG) pathways involved in immunity, anti-inflammation, antioxidants, and lipid metabolism and transport. Furthermore, in terms of placental health, we analyzed the levels of related enzymes, metabolites and mRNA expression in the placenta. Lycopene was shown to reduce mRNA expression and the levels of placental inflammatory factors, increase the content of immunoglobulin, improve the antioxidant capacity, and improve lipid metabolism and lipid transport in the placenta. In terms of sow milk composition, lycopene increased the levels of immunoglobulins in colostrum and lactose in colostrum and milk. Overall, the results of the present study demonstrate that dietary lycopene supplementation of sows during gestation and lactation improves the reproductive performance to a certain extent; this may be due to lycopene improving the placental health and milk composition of sows.