The aims of this study were to evaluate metabolic profiles obtained at −14, 14, and 28 days in milk (DIM), and to identify potential predictive biomarkers of Holstein dairy cows with purulent vaginal ...discharge (PVD) at 28 DIM. The body condition score (BCS) and hematocrit (Hct) were evaluated, and a metabolic profile test (MPT) was performed at −14, 14, and 28 DIM using serum samples. Cows at 28 DIM were classified using a vaginoscopy and divided into groups of healthy cows (n=89) and cows with PVD (n=31). Albumin (Alb), total cholesterol (TCho), calcium (Ca) and, magnesium (Mg) levels were lower in cows with PVD than in healthy cows at 14 DIM. At 28 DIM, levels of Alb, TCho, Ca, blood urea nitrogen (BUN), Mg, and Hct were lower in cows with PVD. A multivariate stepwise logistic regression analysis showed that higher non-esterified fatty acids (NEFA; odds ratios; OR=4.47; P<0.01), lower Alb (OR=0.07; P<0.01) and lower TCho (OR=0.99; P=0.08) at 14 DIM, and lower Hct (OR=0.83; P=0.05), lower Alb (OR=0.12; P<0.01), and lower BUN (OR=0.74; P=0.02) at 28 DIM were significantly associated with PVD. In conclusion, serum Alb levels was a potential indicator associated with PVD, reflecting dietary protein deficiency preceding disease. Our findings suggest that MPT should be considered to monitor health status during the postpartum period for early diagnosis of PVD.
Despite the availability and use of numerous cholesterol-lowering drugs, atherosclerotic cardiovascular disease (ASCVD) remains the leading cause of mortality globally. Many researchers have focused ...their effort on identifying modified lipoproteins. However, lipid moieties such as lysophosphatidylcholine (LPC) and ceramide (CER) contribute to atherogenic events. LPC and CER both cause endothelial mitochondrial dysfunction, leading to fatty acid and triglyceride (TG) accumulation. In addition, they cause immune cells to differentiate into proinflammatory phenotypes. To uncover alternative therapeutic approaches other than cholesterol- and TG-lowering medications, we conducted untargeted lipidomic investigations to assess the alteration of lipid profiles in
knockout (
) mouse model, with or without feeding a high-fat diet (HFD). Results indicated that, in addition to hypercholesterolemia and hyperlipidemia, LPC levels were two to four times higher in
mice compared to wild-type mice in C57BL/6 background, regardless of whether they were 8 or 16 weeks old. Sphingomyelin (SM) and CER were elevated three- to five-fold in
mice both at the basal level and after 16 weeks when compared to wild-type mice. After HFD treatment, the difference in CER levels elevated more than ten-fold. Considering the atherogenic properties of LPC and CER, they may also contribute to the early onset of atherosclerosis in
mice. In summary, the HFD-fed
mouse shows elevated LPC and CER contents and is a suitable model for developing LPC- and CER-lowering therapies.
•A recombinant GnRH-1 fusion protein with the adjuvant MONTANIDE ISA 206 VG is described for GnRH-targeted immunocastration.•Vaccination sustains long-lasting specific anti-GnRH ...antibodies.•Vaccination decreased levels of sexual hormones and cessation of the estrous cycle.•Vaccination induced testicular atrophy, and reduced sperm quality, concentration, morphology, viability.•This vaccine can be utilized in both sexes and different ages.
Immunocastration is an effective alternative to surgical castration for controlling the population of animals. As gonadotropin-releasing hormone (GnRH) regulates the reproductive endocrine system in mammals, it is a target antigen for vaccine formulation. Through this study, we evaluated the effectiveness of a recombinant subunit GnRH-1 vaccine for the immunocastration of the reproductive function of 16 mixed-breed dogs (Canis familiaris) provided voluntarily by different households. All the dogs were deemed clinically healthy prior to and during the experiment. A specific anti-GnRH immune response was detected at Week 4, which was maintained for at least 24 weeks after vaccination. Moreover, decreased levels of sexual hormones (testosterone as well as progesterone and estrogen, respectively) were observed in both male and female dogs. Estrous suppression was apparent in female dogs, and testicular atrophy and poor semen quality (concentration, abnormality, and viability) were observed in male dogs. In conclusion, the recombinant subunit GnRH-1 vaccine could successfully suppress fertility and delay the estrous cycle in canines. These results support the efficacy of the recombinant subunit GnRH-1 vaccine; thus, it is a suitable candidate for fertility control in dogs.
Norovirus is the most common cause of foodborne gastroenteritis, affecting millions of people worldwide annually. Among the ten genotypes (GI-GX) of norovirus, only GI, GII, GIV, GVIII, and GIX ...infect humans. Some genotypes reportedly exhibit post-translational modifications (PTMs), including
- and
-glycosylation,
-GlcNAcylation, and phosphorylation, in their viral antigens. PTMs have been linked to increased viral genome replication, viral particle release, and virulence. Owing to breakthroughs in mass spectrometry (MS) technologies, more PTMs have been discovered in recent years and have contributed significantly to preventing and treating infectious diseases. However, the mechanisms by which PTMs act on noroviruses remain poorly understood. In this section, we outline the current knowledge of the three common types of PTM and investigate their impact on norovirus pathogenesis. Moreover, we summarize the strategies and techniques for the identification of PTMs.
Megakaryocytes in pulmonary diseases Huang, Di-Yun; Wang, Guan-Ming; Ke, Zhuo-Ran ...
Life sciences (1973),
07/2022, Letnik:
301
Journal Article
Recenzirano
Megakaryocytes (MKs) are typical cellular components in the circulating blood flowing from the heart into the lungs. Physiologically, MKs function as an important regulator of platelet production and ...immunoregulation. However, dysfunction in MKs is considered a trigger in various diseases. It has been described that the lung is an important site of platelet biogenesis from extramedullary MKs, which may play an essential role in various pulmonary diseases. With detailed studies, there are different degrees of numerical changes of MKs in coronavirus disease 2019 (COVID-19), acute respiratory distress syndrome (ARDS), chronic obstructive pulmonary disease (COPD), lung cancer, pulmonary fibrosis (PF), and other pulmonary diseases. Also, MKs inhibit or promote the development of pulmonary diseases through various pathways. Here, we summarize the current knowledge of MKs in pulmonary diseases, highlighting the physiological functions and integrated molecular mechanisms. We aim to shine new light on not only the subsequent study of MKs but also the diagnosis and treatment of pulmonary diseases.
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CEMIP is a novel risk factor of various cancers through activating Wnt/β-catenin /epithelial-mesenchymal transition between epithelial cells and stroma. The chronic fibrosis commonly contributes ...renal carcinogenesis in patients with obesity. As there have very few choices of medicines targeting CEMIP. This study intended to design therapeutic DNA vaccines for nephropathy in obesity, through diminishing the CEMIP/Wnt1/β-catenin pathway.
In an 8-week experiment, plasmid-encoding CEMIP was vaccinated into high-fat diet (HFD) or obesity mice in the first 4 weeks, and then vaccination was stopped for at least 4 weeks. Then, plasma and spleens were harvested to evaluate anti-CEMIP antibody synthesis and T-helper type 1 and 2 activation after vaccination. Kidneys were collected to investigate efficacy of CEMIP DNA vaccine on inhibiting HFD and obesity-induced fibrosis and Wnt1/β-catenin pathway. To confirm that CEMIP crucially contributed towards fibrotic formation, CEMIP gene or siRNA transfection was performed in HK-2 cells under VLDL stimulation, or not.
At the end point, anti-CEMIP antibody was successfully produced in the pcDNA 3.1-CEMIP vaccinated group, while Wnt1/β-catenin signaling and fibrosis was inactive. Through VLDL stimulation and CEMIP overexpression, Wnt1/β-catenin signaling and fibrosis significantly presented in vitro. Otherwise, anti-sera of CEMIP-vaccinated mice could inhibit the VLDL-induced Wnt1/β-catenin/fibrosis pathway in HK-2 cells. Similarly, the silencing of CEMIP by siRNA ameliorated the Wnt1/β-catenin pathway and fibrogenesis under VLDL stimulation.
DNA vaccine targeting CEMIP/Wnt1/β-catenin pathway plays a novel strategy in nephropathy.
Immune therapy might provide a new therapeutic option on nephropathy of obesity.
•CEMIP DNA vaccine can prevent high fat diet or obesity-caused renal fibrosis.•CEMIP DNA vaccine efficiently induces humoral immunity for repressing renal fibrosis.•VLDL/CEMIP/Wnt1/β-catenin signaling is a novel pathological pathway in obesity-related chronic kidney diseases (CKD).
Self-amplifying RNA (SaRNA) is a burgeoning platform that exploits the replication machinery of alphaviruses such as Venezuelan equine encephalitis (VEE) virus or Sindbis virus (SIN). SaRNA has been ...used for development of human vaccines, but has not been evaluated for porcine vaccine development. Porcine reproductive and respiratory syndrome virus (PRRSV) causes tremendous economic losses to the worldwide pork industry, but current vaccines trigger delayed neutralizing antibody response and confer only partial protection. Here we first compared two SaRNA systems based on VEE and SIN, and demonstrated that in vitro transcribed VEE-based SaRNA conferred prolonged reporter gene expression and RNA amplification in pig cells with low cytotoxicity, but SIN-based SaRNA imparted evident cytotoxicity and limited gene expression in pig cells. Transfection of VEE-based SaRNA that encodes the major PRRSV antigen dNGP5 (SaRNA-dNGP5) conferred persistent expression for at least 28 days in pig cells. We next complexed SaRNA-dNGP5 with the polyaspartamide block copolymer PEG-PAsp(TEP) to form polyplex nanomicelle with high packaging efficiency and narrow size distribution. The polyplex nanomicelle enabled sustained dNGP5 expression and secretion in vitro. Compared with the commercial PRRS vaccine, nanomicelle delivery of SaRNA-dNGP5 into animal models accelerated the induction of potent neutralizing antibodies with minimal side effects, and elicited stronger IL-4 and IFN-γ responses against homologous and heterologous PRRSV. These properties tackle the problems of current vaccines and implicate the potential of SaRNA-dNGP5 nanomicelle as an effective PRRS vaccine.
Chang et al. developed a SaRNA-based vaccine delivered using polyplex nanomicelle to prolong the antigen expression and enhance humoral/cell-mediated immune responses in animal models. Display omitted
•VEE SaRNA conferred prolonged gene expression and RNA amplification in pig cells with low toxicity.•VEE SaRNA encoding PRRSV antigen dNGP5 conferred expression for >28 days in pig cells.•SaRNA complexed with polyaspartamide block copolymer formed polyplex nanomicelle with high packaging efficiency.•Nanomicelle delivery of SaRNA-dNGP5 in vivo accelerated the induction of anti-PRRSV neutralizing antibodies.•Nanomicelle delivery of SaRNA-dNGP5 elicited strong cellular immune responses against homologous and heterologous PRRSV.
The development of modern technology has posed greater and more urgent needs for thermal management materials. Aligned carbon nanotube arrays and carbon/carbon composites have aroused extensive ...interest as ideal lightweight and stable thermal management materials because of their low thermal expansion coefficient, excellent thermal conduction and high-temperature resistance. Here, we first review the thermal conducting mechanism of carbon materials. We then describe the general fabrication methods, the main factors affecting the thermal conductivity of aligned carbon nanotube arrays and carbon/carbon composites as well as their use in thermal management. The preparation-structure-performance relationships are outlined and the strategies for achieving high thermal conductivity are summarized. Finally, a critical consideration of the challenges and prospects in the thermal management applications of aligned carbon nanotubes and carbon/carbon composites is given.
We documented a case of a free-living Formosan sambar deer (Rusa unicolor swinhoei) infected with a newly discovered ruminant Rhadinovirus (RuRv). Non-purulent encephalitis was the primary ...histological lesion of the sambar deer. We conducted nested PCR to screen for herpesvirus using generic primers targeting the DNA polymerase gene. In addition, we found that DNA polymerase gene of the sambar deer RuRv was present in the macrophage distributed in the Virchow Robin space with histopathologic lesions by chromogenic in-situ hybridization (CISH). The phylogenetic analysis indicated a high similarity between the viral sequence isolated from fallow deer and our case. This result suggests the possibility of cross-species transmission from other exotic Cervidae reservoir to the Formosan sambar deer.
Flagellin activates the immune system through Toll-like receptor 5 (TLR5) and can work as an adjuvant for subunit vaccines. In this study, we tested the adjuvancy of two different N-terminal ...fragments of flagellin, (1) FliC99, residues 1–99, and (2) FliC176, residues 1–176, to incorporate larger areas of the hotspot region for potentially higher levels of TLR5 activation and immune response. A truncated version of the VP2 protein (name tVP2, residues 199–356) of the Infectious bursal disease virus (IBDV) was genetically linked to the flagellin constructs, and the immune response was evaluated in chickens. Results showed that both chimeric antigen–adjuvant constructs increased humoral (total IgG titers), cellular and cytokine immune response (IL-4, IFN-γ). The resulting antibody also successfully neutralized IBDV. We conclude that the N-terminus of flagellin can act as an immune activator to enhance vaccine efficacy.
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