Tolerance is more easily induced in liver transplant models than in other organs; CD8+CD45RClowregulatory T cells (Tregs) have been shown to induce tolerance in heart allografts. Whether ...CD8+CD45RClowTregs could induce tolerance in a liver transplant model and how dendritic cells (DCs) mediate the CD8+CD45RClowTregs effect remains to be investigated.
A rat liver transplantation model was established and used to test tolerance and acute rejection compared to control groups. Liver function and histopathological changes of allograft were examined by enzyme-linked immunosorbent assay (ELISA) and haematoxylin and eosin (H&E) staining, respectively. The distribution and proportion of CD8+CD45RClowTregs and plasmacytoid dendritic cells (pDCs) in the allografts and spleen were determined using flow cytometry. Cytokine secretion levels were determined using ELISA and real-time quantitative PCR (qRT-PCR).
The rat liver transplantation model was well established, with a success rate of 93.3% (28/30). The mean survival time of the tolerant and acute-rejection rats were 156 and 14 days, respectively. The proportions of CD8+CD45RClowTegs were higher in the allografts of tolerant rats than in those of acute-rejection rats (33.1 ± 4.3 and 12.4 ± 4.6, respectively; P = 0.04). Significant accumulation of pDCs was observed in tolerant liver graft rats compared to that in acute-rejection rats (1.46 ± 0.23 and 0.80 ± 0.20, respectively; P = 0.02). Importantly, CD8+CD45RClowTregs were positively associated with the frequency of pDCs (P = 0.001, r2 = 0.775). The protein and mRNA expression of IL-10 and TGF-β in the allograft group were increased, possibly being responsible for tolerance induction.
CD8+CD45RClowT cells interact with pDCs through the induction of IL-10 and TGF-β expression and are responsible for inducing immune tolerance in rat liver transplantation.
•Immune tolerance induction is of great significance to transplant recipients.•CD8+Tregs have a powerful function of inducing immune tolerance.•CD8+Tregs induce the rat liver transplantation tolerance by interacting with pDCs.•CD8+CD45RClowTregs and pDCs are therapeutic potential in anti-transplant rejection.
Recently, rare-earth-activated phosphors have been excessively studied for applications in field of white light-emitting diodes (W-LEDs). In this work, a series of Sm
3+
-doped Na
5
Bi(P
2
O
7
)
2
...phosphors have been synthesized via traditional high-temperature solid-state reaction method. The purity and phase structure were verified by powder X-ray diffraction (XRD) analysis. Owing to the
4
G
5/2
→
6
H
7/2
transition of Sm
3+
, Na
5
Bi
1−
x
Sm
x
(P
2
O
7
)
2
phosphors show intense orange–red emission centered at 600 nm under near-UV light (403 nm) excitation. The 4% Sm
3+
ion is the optimum doping concentration. The concentration quenching dominant mechanism is the d−d interaction. Moreover, phosphors Na
5
Bi
0.96
Sm
0.04
(P
2
O
7
)
2
show good thermal stability, restraining 79.4% at 150 °C of that measured at 25 °C. The CIE coordinates of phosphor Na
5
Bi
0.96
Sm
0.04
(P
2
O
7
)
2
were calculated to be (0.573, 0.414). Therefore, phosphor Na
5
Bi
1−
x
Sm
x
(P
2
O
7
)
2
could be potentially used as an orange–red phosphor for W-LEDs.
Kleine-Levin syndrome (KLS) is a rare disorder of relapsing sleepiness. The hypothesis was that the syndrome is related to a change in the vigilance peptide orexin A.
From 2002 to 2013, 57 patients ...with relapsing hypersomnolence were clinically assessed in a referral academic center in Beijing, China, and 44 (28 males and 16 females; mean age 18.3 ± 8.9 y (mean ± standard deviation, range 9-57 y) were determined to have clinical and behavioral criteria consistent with KLS. Cerebrospinal fluid orexin A levels and diurnal blood pressure were measured in relapse versus remission in a subgroup of patients.
Presenting symptoms included relapsing or remitting excessive sleepiness-associated parallel complaints of cognitive changes (82%), eating disorders (84%); depression (45%); irritability (36%); hypersexuality (18%); and compulsions (11%). Episodes were 8.2 ± 3.3 days in duration. In relapse, diurnal values for blood pressure and heart rate were lower (P < 0.001). In a subgroup (n = 34), cerebrospinal fluid orexin A levels were ∼31% lower in a relapse versus remission (215.7 ± 81.5 versus 319.2 ± 95.92 pg/ml, P < 0.001); in three patients a pattern of lower levels during subsequent relapses was documented.
There are lower orexin A levels in the symptomatic phase than in remission and a fall and rise in blood pressure and heart rate, suggesting a role for orexin dysregulation in KLS pathophysiology.
As a globally complicated disease, malignant tumor has long been posing a threat to human health with increasingly high morbidity and mortality. Notably, existing treatments for tumors like ...chemotherapy generally carry intolerable toxicity, necessitating novel agents balancing safety and potency. Among them, the anti-tumor potency of herbs, featuring few adverse effects and promising efficacy, has attracted much attention recently. Pristimerin, a Quinone formamide triterpenoid compound extracted from Celastraceae and Portulacaceae, carries pronounced anti-tumor activity. It applies to various malignant tumors, including breast cancer, bile duct cancer, gastric cancer, pancreatic cancer, prostate cancer, glioblastoma, colorectal cancer, oral squamous cell carcinoma, cervical cancer, and lung cancer. In state-of-the-art understanding, pristimerin, alone or combined, can inhibit tumor cell proliferation, induce tumor cell apoptosis, inhibit tumor migration and invasion, inhibit angiogenesis, induce tumor cell autophagy, regulate the occurrence of inflammation related tumors, enhance chemosensitivity and regulate tumor microenvironment and immune cells. Despite the abundance of pristimerin-based research, systematic reviews on its anti-tumor mechanism remain needed. This study presented the anti-tumor mechanism of pristimerin by literature review, which might serve as a reference for further research and clinical practice.
•Pristimerin is a natural compound extracted from Celastraceae and Portulacaceae, which has the advantages of high efficiency and high safety.•Pristimerin has great antitumor effect on breast cancer, bile duct cancer, gastric cancer, pancreatic cancer, prostate cancer, glioblastoma, colorectal cancer, oral squamous cell carcinoma, cervical cancer, and lung cancer and other malignant tumors.•Pristimerin exerts anti-tumor effects through various molecular mechanisms.
Spinal cord injury (SCI) often results in spasticity. There is currently no effective therapy for spasticity. Here, we describe a method to efficiently differentiate human pluripotent stem cells from ...spinal GABA neurons. After transplantation into the injured rat spinal cord, the DREADD (designer receptors exclusively activated by designer drug)-expressing spinal progenitors differentiate into GABA neurons, mitigating spasticity-like response of the rat hindlimbs and locomotion deficits in 3 months. Administering clozapine-N-oxide, which activates the grafted GABA neurons, further alleviates spasticity-like response, suggesting an integration of grafted GABA neurons into the local neural circuit. These results highlight the therapeutic potential of the spinal GABA neurons for SCI.
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•Spinal GABA interneurons are efficiently generated from hPSCs•Human GABA neurons synapse with host spinal neurons•Cell transplantation mitigates spasticity in SCI rats•Therapeutic effect of GABA neurons depends on activity of grafted neurons
Gong et al. develop a technology to guide human ESCs and iPSCs to a homogeneous population of functionally specialized spinal somatosensory neurons and to demonstrate the therapeutic potential of the cells for treating spasticity in SCI rats.
In this study, desert grassland, grassland edge, shrubland edge, shrubland were selec-ted as four transition sites in a nearly 30 years typical desert grassland-shrubland mosaic formed by ...anthropogenic shrub introduction. Soil properties and soil microbial characteristics under vegetation patches and bare interspace in each site were investigated to examine the responses of soil nitrogen to the desert grassland-shrubland state transition. It was shown that the aboveground biomass increased with transition from desert grassland to shrubland. Annual herbs increased largely with the introduction of shrubs. Soil moisture, microbial biomass and total nitrogen and carbon decreased with the transition. The abundance of microogranisms was lower in grassland edge and shrubland edge, and then increased in shrubland, which was slightly higher than that of desert grassland. With respect to nitrogen, nitrate content reached the highest level of 28.45 mg N·kg
and ammonium reached the lowest level of 4.81 mg N·kg
in shrubland, which were significantly increased by 52.3% and decreased by 10.4% compared with desert grassland. In addition, soil moisture and microbial biomass nitrogen was positively correlated across all sites. The relationship between mine-ralized nitrogen and soil moisture was non-linear, as they were positively correlated in desert grassland and grassland edge, but negatively correlated in shrubland edge and shrubland. During the 30-year transition from desert grassland to shrubland, our results showed that soil total nitrogen and microbial biomass nitrogen were significantly decreased, but mineralized nitrogen, especially for nitrate, significantly increased over time, indicating that soil nitrification was inhibited in desert grassland but accelerated in shrubland.
Objective
Bupivacaine is an amide local anesthetic with possible side effects that include an irregular heart rate. However, the mechanism of bupivacaine-induced cardiotoxicity has not been fully ...elucidated, thus we aimed to examine this mechanism.
Methods
We performed electrocardiogram recordings to detect action potential waveforms in Sprague Dawley rats after application of bupivacaine, while calcium (Ca2+) currents in neonatal rat ventricular cells were examined by patch clamp recording. Western blot and quantitative real-time polymerase chain reaction assays were used to detect the expression levels of targets of interest.
Results
In the present study, after application of bupivacaine, abnormal action potential waveforms were detected in Sprague Dawley rats by electrocardiogram recordings, while decreased Ca2+ currents were confirmed in neonatal rat ventricular cells by patch clamp recording. These alterations may be attributed to a deficiency of CaV1.3 (L-type) Ca2+ channels, which may be regulated by the multifunctional protein calreticulin.
Conclusions
The present study identifies a possible role of the calreticulin–CaV1.3 axis in bupivacaine-induced abnormal action potentials and Ca2+ currents, which may lead to a better understanding anesthetic drug-induced cardiotoxicity.
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