Toll-like receptor-4 antagonism mediates benefits during neuroinflammation

Neuroinflammation following immune activation in the central nervous system（CNS）leads to neuronal loss in specific areas of the CNS resulting in neurodegenerative disorders.Thus,fine tuning the immune responses within the brain is essential,because most of the brain diseases are associated with chronic inflammation,

Unmasking the responses of the stem cells and progenitors in the subventricular zone after neonatal and pediatric brain injuries

There is great interest in the regenerative potential of the neural stem cells and progenitors that populate the subventricular zone（SVZ）. However, a comprehensive understanding of SVZ cell responses to brain injuries has been hindered by the lack of sensitive approaches to study the cellular composition of this niche. Here we review progress being made in deciphering the cells of the SVZ gleaned from the use of a recently designed flow cytometry panel that allows SVZ cells to be parsed into multiple subsets of progenitors as well as putative stem cells. We review how this approach has begun to unmask both the heterogeneity of SVZ cells as well as the dynamic shifts in cell populations with neonatal and pediatric brain injuries. We also discuss how flow cytometric analyses also have begun to reveal how specific cytokines, such as Leukemia inhibitory factor are coordinating SVZ responses to injury.

Apelin activates the expression of inflammatory cytokines in microglial BV2 cells via PI-3K/Akt and MEK/Erk pathways

This paper aims to observe the changes of the inflammatory cytokines in microglial BV2 cells stimulated by apelin, and inves- tigate the mechanism of inflammatory cytokines secretion after apelin stimulation. Immunofluorescence and quantitative re- al-time PCR were performed to observe expression of TNF-α, IL-Iβ, IL-10, MIP-let, and MCP-1 in BV2 cells. Western blot was used to investigate the expression of phosphorylation PI-3K/Akt and phosphorylation Erk signaling pathways in BV2 cells after stimulation by apelin. Furthermore, PI-3K/Akt inhibitor （LY294402） and Erk inhibitor （U0126） were used as antagonists to detect the secretion mechanisms of cytokines in BV2 cells stimulated by apelin. Exogenous recombinant apelin activated the expression of TNF-α, IL-1β, MCP-1 and MIP-1α in BV2 cells by the detection of fluorescence expression and mRNA. Apelin also unregulated the protein expression of p-PI-3K/Akt and p-Erk in BV2 cells induced by apelin. LY294002 and U0126 in- hibited activation of p-PI-3K/Akt and p-Erk expression by Western blot and attenuated the expression of inflammation factors in BV2 cells by fluorescence staining. This study demonstrates that apelin is a potential activator of inflammation factors through the PI3K/Akt and Erk signaling pathway and is potential therapeutically relevant to inflammatory responses of micro- glia cells.

Prevention and treatment of cancer targeting chronic inflammation:research progress,potential agents,clinical studies and mechanisms

Numerous experimental and clinical studies indicate that chronic inflammation is closely related to the initiation, progression,and spread of cancer, in which proinflammatory cytokines, such as interleukin(IL)-6, IL-1β, and tumor necrosis factor-α(TNF-α), and transcription factors, such as nuclear factor-κB(NF-κB), and signal transducer and activator of transcription 3(STAT3), play pivotal roles. Stimulated by proinflammatory cytokines, NF-κB and STAT3 can modulate the expression of target genes, most of which are oncogenic ones, and promote the survival, proliferation, invasion, and metastasis of cancer cells. Now it is generally accepted that inflammation-related molecules and pathways are useful targets for the prevention and treatment of cancer. In this review, we summarize the relationship between chronic inflammation and cancer and describe some potentially useful agents including aspirin, meformin, statins, and some natural products(green tea catechins, andrographolide,curcumin) for their cancer prevention and treatment activities targeting chronic inflammation. The results of typical clinical studies are included, and the influences of these agents on the proinflammatory cytokines and inflammation-related pathways are discussed. Data from the present review support that agents targeting chronic inflammation may have a broad application prospect for the prevention and treatment of cancer in the future.

Research on airway inflammation: present status in China's Mainland

Airway inflammation involving activated eosinophils, mast cells and T lymphocytes is an established feature of asthma and has been the key target to treatment. Airway structural changes that occur in patients with asthma in response to persistent inflammation are termed airway remodeling. These findings are documented in studies reaching back more than 20 years. However, among investigators concerning on asthma, airway inflammation and subsequent remodeling as a target of investigation was hardly a blip on the radar screen until a few years ago. Now the subject is of expanding concern to respiratory researchers of many stripes and persuasions, as judged by the rapid rise in the number of publications. Symposia, workshops, lectures, reviews, and grant proposal on this subject also are surging.This review will not attempt to provide a comprehensive description of all aspects of airway inflammation. Rather, it will focus on current data studied by Chinese researchers in the last few years, in which the depth and scope of the discussions were much more profound than before.

Wear particle-mediated expressions of pro-inflammatory cytokines, NF-κB and RANK were impacted by lanthanum chloride in RAW264.7 cells

To explore the impact of different concentrations of lanthanum chloride （LaC13） on critical components of wear particle-mediated signaling pathways in inflammation and osteoclastogenesis, RAW264.7 cells were naturally divided into eight groups and analyzed by CCK-8 assay, flow cytometry, ELISA, RT-PCR and western blot after treatments. The results showed that three concentrations of LaCI3 had no influence on viability of RAW264.7 cells and down-regulated receptor activator of nuclear factor rd3 （RANK） instead of macrophage colony-stimulating factor receptor （M-CSFR）. Additionally, 2.5 and 10 pmol/L LaC13 could signifi- cantly inhibit gene and protein levels of pro-inflammatory cytokines （tumor necrosis factor-or and interleukin-113, i.e., TNF-ct and IL-113） and NF-r,B/p65, but 100 pmol/L LaC13 did not exert an obvious inflammation-inhibiting effect, and even induced inflamma- tion. In conclusion, these findings demonstrated that LaC13 was able to suppress wear particle-induced inflammation and activation of NF-rd3 in a certain range of concentrations in vitro and mainly decrease the expression of RANK, but not M-CSFR, all of which were generally recognized to play a pivotal role in osteoclastogenesis.

Prostate-derived IL-1βupregulates expression of NMDA receptor in the paraventricular nucleus and shortens ejaculation latency in rats with experimental autoimmune prostatitis

Experimental autoimmune prostatitis(EAP)-induced persistent inflammatory immune response can significantly upregulate the expression of N-methyl-D-aspartic acid(NMDA)receptors in the paraventricular nucleus(PVN).However,the mechanism has not yet been elucidated.Herein,we screened out the target prostate-derived inflammation cytokines(PDICs)by comparing the inflammatory cytokine levels in peripheral blood and cerebrospinal fluid(CSF)between EAP rats and their controls.After identifying the target PDIC,qualified males in initial copulatory behavior testing(CBT)were subjected to implanting tubes onto bilateral PVN.Next,they were randomly divided into four subgroups(EAP-1,EAP-2,Control-1,and Control-2).After 1-week recovery,EAP-1 rats were microinjected with the target PDIC inhibitor,Control-1 rats were microinjected with the target PDIC,while the EAP-2 and Control-2 subgroups were only treated with the same amount of artificial CSF(aCSF).Results showed that only interleukin-1β(IL-1β)had significantly increased mRNA-expression in the prostate of EAP rats compared to the controls(P<0.001)and significantly higher protein concentrations in both the serum(P=0.001)and CSF(P<0.001)of the EAP groups compared to the Control groups.Therefore,IL-1βwas identified as the target PDIC which crosses the blood-brain barrier,thereby influencing the central nervous system.Moreover,the EAP-1 subgroup displayed a gradually prolonged ejaculation latency(EL)in the last three CBTs(all P<0.01)and a significantly lower expression of NMDA NR1 subunit in the PVN(P=0.043)compared to the respective control groups after a 10-day central administration of IL-1βinhibitors.However,the Control-1 subgroup showed a gradually shortened EL(P<0.01)and a significantly higher NR1 expression(P=0.004)after homochronous IL-1βadministration.Therefore,we identified IL-1βas the primary PDIC which shortens EL in EAP rats.However,further studies should be conducted to elucidate the specific molecular mechanisms through which IL-1βupregulates NMDA expression.

The role of exercise in rehabilitation of discharged COVID-19 patients

Severe acute respiratory syndrome coronavirus 2(SARS-CoV-2)mainly caused pneumonia and pulmonary fibrosis through upper respiratory tract infection,which resulted in acute respiratory distress syndrome(ARDS)and multiorgan damage of cardiovascular,nervous,digestive,and genitourinary systems.Although the virus test turned negative after the patient recovered,the damage to multiorgan caused by SARS-CoV-2 may irreversible.Therefore,the health status of the recovered patients has gradually become the focus of people's attention.Whether coronavirus disease 2019(COVID-19)patients can receive exercise rehabilitation training after discharge?and what's the basis?We try to analyze and answer these questions,will provide some ideas about the patients to develop a reasonable and effective exercise rehabilitation program.