Primary liver cancer (PLC) is one of the most common malignancies in China, where it ranks second in mortality and fifth in morbidity. Currently, liver transplantation, hepatic tumor resection, ...radiofrequency ablation, and molecular-targeted agents are the major treatments for hepatocellular carcinoma (HCC). Overall, HCC has a poor survival rate and a high recurrence rate. Tumor-infiltrating lymphocytes (TILs) have been discovered to play essential roles in the development, prognosis, and immunotherapy treatment of HCC. As the major component cells of TILs, T cells are also proved to show antitumor and protumor effects in HCC. Foxp3+, CD8+, CD3+, and CD4+ T lymphocytes are the broadly studied subgroups of TILs. This article reviews the roles and mechanisms of different tumor-infiltrating T lymphocyte subtypes in HCC.
•·Astrocyte-derived CCL2 is involved in surgery-induced cognitive dysfunction and neuroinflammation via evoking microglia activation.•·The CCR2 antagonist RS504393 alleviates cognitive decline and ...neuroinflammation following surgery.•·CCL2-CCR2 signaling is a possible mechanism of astrocyte-microglial communication in the CNS.
Neuroinflammation induced by peripheral trauma plays a key role in the development of postoperative cognitive dysfunction (POCD). Substantial evidence points to reactive glia as a pivotal factor during the inflammation process. However, little is known about the functional interactions between astrocytes and microglia. Recent evidence suggests the involvement of the CCL2-CCR2 pathway in CNS inflammation-related diseases. Our previous studies have suggested that astrocyte-derived CCL2 can induce microglial activation in vitro. Within this context, we sought to determine if the CCL2/CCR2 axis is involved in the crosstalk between astrocytes and microglia, contributing to increased neuroinflammation. Here, we show that tibial fracture surgery promoted CCL2 upregulation in activated astrocytes, increased CCR2 expression in activated microglia, and induced deficits in learning and memory. Site-directed pre-injection of RS504393, a CCR2 antagonist, inhibited this effect by reducing microglial activation, M1 polarization, inflammatory cytokines, and neuronal injury and death and improving cognitive function. Taken together, these data implicate CCL2-CCR2 signaling in astrocyte-mediated microglial activation in central nervous system (CNS) inflammation and suggest that interference with CCL2 signaling could constitute another potential therapeutic target for POCD.
Postoperative cognitive dysfunction (POCD) is a common postoperative central nervous system complication, especially in the elderly. It has been consistently reported that the pathological process of ...this clinical syndrome is related to neuroinflammation and microglial proliferation. Glycogen synthase kinase 3β (GSK-3β) is a widely expressed kinase with distinct functions in different types of cells. The role of GSK-3β in regulating innate immune activation has been well documented, but as far as we know, its role in POCD has not been fully elucidated. Lithium chloride (LiCl) is a widely used inhibitor of GSK-3β, and it is also the main drug for the treatment of bipolar disorder. Prophylactic administration of lithium chloride (2 mM/kg) can inhibit the expression of proinflammatory mediators in the hippocampus, reduce the hippocampal expression of NF-κB, and increase both the downregulation of M1 microglial-related genes (inducible nitric oxide synthase and CD86) and upregulation of M2 microglial-related genes (IL-10 and CD206), to alleviate the cognitive impairment caused by orthopedic surgery. In vitro, LiCl reversed LPS-induced production of proinflammatory mediators and M1 polarization of microglia. To sum up these results, GSK-3β is a key contributor to POCD and a potential target of neuroprotective strategies.
Critical-sized bone defect repair in patients with diabetes mellitus remains a challenge in clinical treatment because of dysfunction of macrophage polarization and the inflammatory microenvironment ...in the bone defect region. Three-dimensional (3D) bioprinted scaffolds loaded with live cells and bioactive factors can improve cell viability and the inflammatory microenvironment and further accelerating bone repair. Here, we used modified bioinks comprising gelatin, gelatin methacryloyl (GelMA), and 4-arm poly (ethylene glycol) acrylate (PEG) to fabricate 3D bioprinted scaffolds containing BMSCs, RAW264.7 macrophages, and BMP-4-loaded mesoporous silica nanoparticles (MSNs). Addition of MSNs effectively improved the mechanical strength of GelMA/gelatin/PEG scaffolds. Moreover, MSNs sustainably released BMP-4 for long-term effectiveness. In 3D bioprinted scaffolds, BMP-4 promoted the polarization of RAW264.7 to M2 macrophages, which secrete anti-inflammatory factors and thereby reduce the levels of pro-inflammatory factors. BMP-4 released from MSNs and BMP-2 secreted from M2 macrophages collectively stimulated the osteogenic differentiation of BMSCs in the 3D bioprinted scaffolds. Furthermore, in calvarial critical-size defect models of diabetic rats, 3D bioprinted scaffolds loaded with MSNs/BMP-4 induced M2 macrophage polarization and improved the inflammatory microenvironment. And 3D bioprinted scaffolds with MSNs/BMP-4, BMSCs, and RAW264.7 cells significantly accelerated bone repair. In conclusion, our results indicated that implanting 3D bioprinted scaffolds containing MSNs/BMP-4, BMSCs, and RAW264.7 cells in bone defects may be an effective method for improving diabetic bone repair, owing to the direct effects of BMP-4 on promoting osteogenesis of BMSCs and regulating M2 type macrophage polarization to improve the inflammatory microenvironment and secrete BMP-2.
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•The GelMA/gelatin/PEG/MSN composite bioinks showed satisfactory printability, mechanical stability, and biocompatibility.•The sustained release of BMP-4 from MSNs induced M2 macrophage polarization and thereby inhibited inflammatory reactions.•Loading of BMP-4 and secretion of BMP-2 by M2 type macrophages accelerated bone repair in DM bone defects.
Late preterm infants (LPIs) are at risk of neurodevelopmental delay. Research on their cognitive development is helpful for early intervention and follow-up.
Event-related potential (ERP) and resting ...electroencephalography (RS-EEG) were used to study the brain cognitive function of LPIs in the early stage of life. The Gesell Developmental Scale (GDS) was used to track the neurodevelopmental status at the age of 1 year after correction, and to explore the neurophysiological indicators that could predict the outcome of cognitive development in the early stage.
The results showed that mismatch response (MMR) amplitude, RS-EEG power spectrum and functional connectivity all suggested that LPIs were lagging behind. At the age of 1 year after correction, high-risk LPIs showed no significant delay in gross motor function, but lagged behind in fine motor function, language, personal social interaction and adaptability. The ROC curve was used to evaluate the predictive role of MMR amplitude in the brain cognitive development prognosis at 1 year, showing a sensitivity of 80.00% and a specificity of 90.57%. The area under the curve (AUC) was 0.788, with a P-value of 0.007.
Based on our findings we supposed that the cognitive function of LPI lags behind that of full-term infants in early life. Preterm birth and perinatal diseases or high risk factors affected brain cognitive function in LPIs. MMR amplitude can be used as an early predictor of brain cognitive development in LPIs.
This clinical trial is registered with the Chinese Clinical Trial Registry (ChiCTR).
ChiCTR2100041929. Date of registration: 2021-01-10. URL of the trial registry record: https://www.chictr.org.cn/ .
ABSTRACTChina’s Earth Observation(EO) System has undergone significant development since the 1970s, as China has dedicated substantial efforts to advancing remote sensing technology. With fifty years ...of development, China has successfully narrowed the remote sensing technology gap with foreign countries through collaborative endeavors of the government and enterprises. At present, China has constructed a comprehensive EO system that has been proven indispensable for driving economic growth and facilitating sustainable development. This paper provides an overview of the development, missions, andapplications of China’s EO system, while also exploring future directions and technical trends of China’s EO system.
Background/Aims: Microglia are an essential player in central nervous system inflammation. Recent studies have demonstrated that the astrocytic chemokine, CCL2, is associated with microglial ...activation in vivo. However, CCL2-induced microglial activation has not yet been studied in vitro. The purpose of the current study was to understand the role of astrocyte-derived CCL2 in microglial activation and to elucidate the underlying mechanism(s). Methods: Primary astrocytes were pre-treated with CCL2 siRNA and stimulated with TNF-α. The culture medium (CM) was collected and added to cultures of microglia, which were incubated with and without CCR2 inhibitor. Microglial cells were analyzed by quantitative RT-PCR to determine whether they polarized to the M1 or M2 state. Microglial migratory ability was assessed by transwell migration assay. Results: TNF-α stimulated the release of CCL2 from astrocytes, even if the culture media containing TNF-α was replaced with fresh media after 3 h. CM from TNF-α-stimulated astrocytes successfully induced microglial activation, which was ascertained by increased activation of M1 and enhanced migration ability. In contrast, CM from astrocytes pretreated with CCL2 siRNA showed no effect on microglial activation, compared to controls. Additionally, microglia pre-treated with RS102895, a CCR2 inhibitor, were resistant to activation by CM from TNF-α-stimulated astrocytes. Conclusion: This study demonstrates that the CCL2/CCR2 pathway of astrocyte-induced microglial activation is associated with M1 polarization and enhanced migration ability, indicating that this pathway could be a useful target to ameliorate inflammation in the central nervous system.
Abstract Background Laparoscopic partial hepatectomy inevitably decrease patient immune function. Propofol has been shown to have immunomodulatory effects but is associated with hemodynamic side ...effects. Despite studies showing a negligible impact of remimazolam tosylate on hemodynamics, it has not been reported for partial hepatectomy patients. Its influence on immune function also remains unexplored. This study sought to investigate the differences in immune function and intraoperative hemodynamics between patients who underwent laparoscopic partial hepatectomy with remimazolam tosylate and those who underwent laparoscopic partial hepatectomy with propofol. Methods This was a single-center, randomized controlled trial involving 70 patients, who underwent elective laparoscopic partial hepatectomy. The patients were randomly divided into two groups: the remimazolam group (group R) and the propofol group (group P). In this study, the primary outcomes assessed included the patient’s immune function and hemodynamic parameters, and the secondary outcomes encompassed the patient’s liver function and adverse events. Results Data from 64 patients (group R, n = 31; group P, n = 33) were analyzed. The differences in the percentages of CD3 + , CD4 + , CD8 + , and NK cells and the CD4 + /CD8 + ratio between the two groups were not statistically significant at 1 day or 3 days after surgery. Compared with those in group P, the MAP and HR at T2 and the MAP at T1 in group R were significantly increased( P < 0.05). The differences in HR and MAP at T0, T3, T4, T5, T6, and T7 and HR at T1 between the two groups were not statistically significant. There were no differences in liver function or adverse effects between the two groups, suggesting that remimazolam tosylate is a safe sedative drug( P > 0.05). Conclusion The effects of remimazolam tosylate on the immune function of patients after partial hepatectomy are comparable to those of propofol. Additionally, its minimal effect on hemodynamics significantly decreases the incidence of hypotension during anesthesia induction, thereby enhancing overall perioperative safety. Trial registration The trial was registered on May 9, 2022 in the Chinese Clinical Trial Registry, registration number ChiCTR2200059715 (09/05/2022).
Abstract Bacteria utilize intercellular communication to orchestrate essential cellular processes, adapt to environmental changes, develop antibiotic tolerance, and enhance virulence. This ...communication, known as quorum sensing (QS), is mediated by the exchange of small signalling molecules called autoinducers. AI-2 QS, regulated by the metabolic enzyme LuxS (S-ribosylhomocysteine lyase), acts as a universal intercellular communication mechanism across gram-positive and gram-negative bacteria and is crucial for diverse bacterial processes. In this study, we demonstrated that in Streptococcus suis ( S. suis ), a notable zoonotic pathogen, AI-2 QS enhances galactose utilization, upregulates the Leloir pathway for capsular polysaccharide (CPS) precursor production, and boosts CPS synthesis, leading to increased resistance to macrophage phagocytosis. Additionally, our molecular docking and dynamics simulations suggest that, similar to S. pneumoniae , FruA, a fructose-specific phosphoenolpyruvate phosphotransferase system prevalent in gram-positive pathogens, may also function as an AI-2 membrane surface receptor in S. suis . In conclusion, our study demonstrated the significance of AI-2 in the synthesis of galactose metabolism-dependent CPS in S. suis . Additionally, we conducted a preliminary analysis of the potential role of FruA as a membrane surface receptor for S. suis AI-2.
Porcine epidemic diarrhea virus (PEDV) is an α-coronavirus that causes highly contagious intestinal infectious disease, involving clinically characterized by diarrhea, dehydration, vomiting, and high ...mortality to suckling piglets. As a strategy for antiviral therapy, artificial microRNA (amiRNA) mediated suppression of viral replication has recently become increasingly important. In this study, we evaluated the advantages of using an amiRNA vector against PEDV.
In this study, we evaluated the advantages of using an amiRNA vector against PEDV. We designed two single amiRNA sequences for different conserved sequences of the PEDV S and N genes, and tested their inhibitory effects on PEDV in Vero cells.
It was obvious from the CCK-8 results that the transient transfection of amiRNA was non-toxic to the cells. In addition, our results showed that the transient expression of two amiRNAs (amiRNA-349 and amiRNA-1447) significantly reduced the expression of viral RNA and protein in the cells. The TCID
results showed that the release of virus particles into the culture supernatant was significantly reduced, with an effect as high as 90%. To avoid virus mutation escape, the above two single amiRNA sequences were tandem in this study (amiRNA-349 + 1447), enabling a single microRNA to be expressed simultaneously. The real-time PCR and Western blot results showed that the inhibitory effect was significantly enhanced in each of the different time periods. The TCID
results showed that the release of virus particles in the culture supernatant was significantly reduced at the different time periods.
In summary, these results suggest that an RNAi based on amiRNA targeting the conserved region of the virus is an effective method to improve PEDV nucleic acid inhibitors and provide a novel treatment strategy for PEDV infection.
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