Background
Mesenchymal stem cell (MSC) infusion was reported to improve liver function in patients with decompensated liver cirrhosis (DLC); however, whether the medication can improve outcome of ...these patients is poorly understood.
Methods
This prospective, open-labeled, randomized controlled study enrolled 219 patients with HBV-related DLC who were divided into control group (
n
= 111) and umbilical cord-derived MSC (UC-MSC)-treated group (
n
= 108), then all of them received a follow-up check from October 2010 to October 2017. The treated patients received three times of UC-MSC infusions at 4-week intervals plus conventional treatment that was only used for control group. The overall survival rate and HCC-free survival rate were calculated as primary endpoints and the liver function and adverse events associated with the medication were also evaluated.
Results
During the follow-up check period from 13 to 75th months, there was a significantly higher overall survival rate in the treated group than the control group, while the difference of the hepatocellular carcinoma event-free survival rate between the treated and control groups was not observed during the 75-month follow-up. UC-MSC treatment markedly improved liver function, as indicated by the levels of serum albumin, prothrombin activity, cholinesterase, and total bilirubin during 48 weeks of follow-up. No significant side effects or treatment-related complications were observed in the UC-MSC group.
Conclusions
Therapy of UC-MSC is not only well tolerated, but also significantly improves long-term survival rate, as well as the liver function in patients with HBV-related DLC. UC-MSC medication, therefore, might present a novel therapeutic approach for the disease.
Graphic abstract
Progesterone is required for the establishment and maintenance of mammalian pregnancy and widely used for conservative treatment of luteal phase deficiency in clinics. However, there are limited ...solid evidences available for the optimal timing and dose of progesterone therapy, especially for the possible adverse effects on implantation and decidualization when progesterone is administrated empirically. In our study, mouse models were used to examine effects of excess progesterone on embryo implantation and decidualization. Our data indicate that excess progesterone is not only harmful for mouse implantation, but also impairs mouse decidualization. In excess progesterone-treated mice, the impaired LIF/STAT3 pathway and dysregulated endoplasmic reticulum stress may lead to the inhibition of embryo implantation and decidualization. It is possible that the decrease in birth weight of excess progesterone-treated mice is due to a compromised embryo implantation and decidualization. Furthermore, excess progesterone compromises in vitro decidualization of human endometrial stromal cells.
Extensive mononuclear cell infiltration is strongly correlated with liver damage in patients with chronic hepatitis B virus (CHB) infection. Macrophages and infiltrating monocytes also participate in ...the development of liver damage and fibrosis in animal models. However, little is known regarding the immunopathogenic role of peripheral blood monocytes and intrahepatic macrophages.
The frequencies, phenotypes, and functions of peripheral blood and intrahepatic monocyte/macrophage subsets were analyzed in 110 HBeAg positive CHB patients, including 32 immune tolerant (IT) carriers and 78 immune activated (IA) patients. Liver biopsies from 20 IA patients undergoing diagnosis were collected for immunohistochemical analysis. IA patients displayed significant increases in peripheral blood monocytes and intrahepatic macrophages as well as CD16(+) subsets, which were closely associated with serum alanine aminotransferase (ALT) levels and the liver histological activity index (HAI) scores. In addition, the increased CD16(+) monocytes/macrophages expressed higher levels of the activation marker HLA-DR compared with CD16(-) monocytes/macrophages. Furthermore, peripheral blood CD16(+) monocytes preferentially released inflammatory cytokines and hold higher potency in inducing the expansion of Th17 cells. Of note, hepatic neutrophils also positively correlated with HAI scores.
These distinct properties of monocyte/macrophage subpopulations participate in fostering the inflammatory microenvironment and liver damage in CHB patients and further represent a collaborative scenario among different cell types contributing to the pathogenesis of HBV-induced liver disease.
Interleukin‐17 (IL‐17)‐producing CD4+ T cells (Th17)‐mediated immune response has been demonstrated to play a critical role in inflammation‐associated disease; however, its role in chronic hepatitis ...B virus (HBV) infection remains unknown. Here we characterized peripheral and intrahepatic Th17 cells and analyzed their association with liver injury in a cohort of HBV‐infected patients including 66 with chronic hepatitis B (CHB), 23 with HBV‐associated acute‐on‐chronic liver failure (ACLF), and 30 healthy subjects as controls. The frequency of circulating Th17 cells increased with disease progression from CHB (mean, 4.34%) to ACLF (mean, 5.62%) patients versus healthy controls (mean, 2.42%). Th17 cells were also found to be largely accumulated in the livers of CHB patients. The increases in circulating and intrahepatic Th17 cells positively correlated with plasma viral load, serum alanine aminotransferase levels, and histological activity index. In vitro, IL‐17 can promote the activation of myeloid dendritic cells and monocytes and enhance the capacity to produce proinflammatory cytokines IL‐1β, IL‐6, tumor necrosis factor (TNF)‐α, and IL‐23 in both CHB patients and healthy subjects. In addition, the concentration of serum Th17‐associated cytokines was also increased in CHB and ACLF patients. Conclusion: Th17 cells are highly enriched in both peripheral blood and liver of CHB patients, and exhibit a potential to exacerbate liver damage during chronic HBV infection. (HEPATOLOGY 2009.)
ion of iodide from (η5‐C5iPr5)2UI (1) produced the cationic uranium(III) metallocene (η5‐C5iPr5)2U+ (2) as a salt of B(C6F5)4−. The structure of 2 consists of unsymmetrically bonded cyclopentadienyl ...ligands and a bending angle of 167.82° at uranium. Analysis of the bonding in 2 showed that the uranium 5f orbitals are strongly split and mixed with the ligand orbitals, thus leading to non‐negligible covalent contributions to the bonding. Investigation of the dynamic magnetic properties of 2 revealed that the 5f covalency leads to partially quenched anisotropy and fast magnetic relaxation in zero applied magnetic field. Application of a magnetic field leads to dominant relaxation by a Raman process.
Uranium sandwiches: ion of iodide from (η5‐C5iPr5)2UI produced the cationic uranium(III) metallocene (η5‐C5iPr5)2U+ as its B(C6F5)4− salt (see scheme). Appreciable covalency involving 5f and 6d orbitals in the uranocenium cation partially quenched the orbital angular momentum and led to slow magnetic relaxation in an applied field by a Raman mechanism.
The field-induced blockage of magnetization behavior was first observed in an YbIII-based molecule with a trigonally distorted octahedral coordination environment. Ab initio calculations and ...micro-SQUID measurements were performed to demonstrate the exhibition of easy-plane anisotropy, suggesting the investigated complex is the first pure lanthanide field-induced single-ion magnet (field-induced SIM) of this type. Furthermore, we found the relaxation time obeys a power law instead of an exponential law, indicating that the relaxation process should be involved a direct process rather than an Orbach process.
The purpose of this study is to develop an anti-PDL1-based interferon (IFN) fusion protein to overcome the chronic hepatitis B virus (HBV)-induced immune tolerance, and combine this immunotherapy ...with a HBV vaccine to achieve the functional cure of chronic hepatitis B (CHB) infection.
We designed an anti-PDL1-IFNα heterodimeric fusion protein, in which one arm was derived from anti-PDL1 antibody and the other arm was IFNα, to allow targeted delivery of IFNα into the liver by anti-PDL1 antibody. The effect of the anti-PDL1-IFNα heterodimer on overcoming hepatitis B surface antigen (HBsAg) vaccine resistance was evaluated in chronic HBV carrier mice.
The anti-PDL1-IFNα heterodimer preferentially targeted the liver and resulted in viral suppression, the PD1/PDL1 immune checkpoint blockade and dendritic cell activation/antigen presentation to activate HBsAg-specific T cells, thus breaking immune tolerance in chronic HBV carrier mice. When an HBsAg vaccine was administered soon after anti-PDL1-IFNα heterodimer treatment, we observed strong anti-HBsAg antibody and HBsAg-specific T cell responses for efficient HBsAg clearance in chronic HBV carrier mice that received the combination treatment but not in those that received either single treatment.
Targeting the liver with an engineered anti-PDL1-IFNα heterodimer can break HBV-induced immune tolerance to an HBsAg vaccine, offering a promising translatable therapeutic strategy for the functional cure of CHB.
Discoveries of tetraquarks not only enrich the hadronic spectrum but also provide more platforms to understand quantum chromodynamics. We study the production processes of hidden-charm and open-charm ...tetraquarks in
B
decays by analyzing their topological amplitudes. Relations between different channels are found, which confront tests by experiments to probe the nature of the tetraquarks. Furthermore, promising channels to find more tetraquarks are proposed.
A 16-channel closed-loop neuromodulation system-on-chip (SoC) for human epileptic seizure control is proposed and designed. In the proposed SoC, a 16-channel neural-signal acquisition unit (NSAU), a ...biosignal processor (BSP), a 16-channel high-voltage-tolerant stimulator (HVTS), and wireless power and bidirectional data telemetry are designed. In the NSAU, the input protection circuit is used to prevent MOSFET from overstressing by the high-voltage stimulations. Hence, NSAUs can share electrodes with stimulators. The auto-reset chopper-stabilized capacitive-coupled instrumentation amplifiers (AR-CSCCIAs) are designed with the chopper-stabilized technique with a new offset reduction loop. The measured input-referred noise is 2.09 <inline-formula> <tex-math notation="LaTeX">\mu \textrm {V}_{\mathrm {rms}} </tex-math></inline-formula> and the noise-efficiency factor (NEF) is 3.78. The entropy-and-spectrum seizure detection algorithm is implemented in the BSP with 0.76-s seizure detection latency and 97.8% detection accuracy. When the seizure onset is detected by the BSP, the HVTS with adaptive supply control delivers 0.5-3-mA biphasic current stimulation to suppress the seizure onset. The proposed SoC is powered wirelessly, and the bidirectional data telemetry is realized through the same pair of coils in 13.56 MHz. The downlink data rate is 211 Kb/s with the binary phase-shift keying (BPSK) modulation and a new BPSK demodulator. The uplink data rate is 106 Kb/s with the load-shift keying (LSK) modulation. The proposed SoC is fabricated in a 0.18-<inline-formula> <tex-math notation="LaTeX">\mu \text{m} </tex-math></inline-formula> CMOS technology and occupies 25 mm 2 . Electrical tests have been performed to characterize the SoC performance. In vivo animal experiments using mini-pigs have been performed to successfully verify the closed-loop neuromodulation functions on epileptic seizure suppression.
Benefiting from a quasi-passivated film, as-solutionized Mg-Sm-Zn-Zr alloy exhibits an extraordinary corrosion resistance over currently reported Mg alloys. The breakdown potential and corrosion ...current density are respectively −1.208 VSCE and 3.9 μA/cm2 after 24 h immersion in 0.6 M NaCl solution. The film consists of an outer layer, an intermediate layer and a Zn-rich layer. The oxide of solute element Sm strengthens the intermediate layer, which plays the primary role of impeding corrosion, by filling the vacancies left by the selective dissolution of Mg. An approximate linearity exists between the film resistance and the thickness of the intermediate layer.
Display omitted
•A quasi-passivated film is formed on as-solutionized Mg-Sm-Zn-Zr alloy in NaCl solution.•The tri-structure film is composed of outer, intermediate and Zn-rich inner layer.•The in-situ transformation of Sm in intermediate layer plays the critical role.•Protectiveness of the surface film is nearly linear to the thickness of the intermediate layer.•The inner Zn-rich layer is formed by a dissolution-reduction process.
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