Cheng-You Lu

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood–brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigated pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4/MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

Angiostrongylus cantonensis, a zoonotic parasite, can invade the human central nervous system (CNS) and cause acute eosinophilic meningitis or eosinophilic meningoencephalitis. Mice infected with A. cantonensis show elevated levels of pro-inflammatory cytokines, plasminogen activators, and matrix metalloproteinase-9, resulting in disruption of the blood-brain barrier (BBB) and immune cell infiltration into the CNS. Caveolin-1 (Cav-1) regulates the permeability of the BBB, which affects immune cells and cerebrospinal fluid. This intricate interaction ultimately fuels the progression of brain damage and edema. This study aims to investigate the regulatory role of Cav-1 in the pathogenesis of meningoencephalitis induced by A. cantonensis infection. We investigate pathological alterations by triphenyl-tetrazolium chloride, brain water content, BBB permeability, Western blot analysis, and gelatin zymography in BALB/c mice after A. cantonensis. The study evaluates the critical role of Cav-1 regulation through the TLR4 / MyD88 signaling pathway, modulates tight junction proteins, influences BBB permeability, and contributes to brain damage in A. cantonensis-induced meningoencephalitis.

Heat shock proteins (HSPs), which function as chaperones, are activated in response to various environmental stressors. In addition to their role in diverse aspects of protein production, HSPs protect against harmful protein-related stressors. Calycosin exhibits numerous beneficial properties. This study aims to explore the protective effects of calycosin in the heart under heat shock and determine its underlying mechanism. H9c2 cells, western blot, TUNEL staining, flow cytometry, and immunofluorescence staining were used. The time-dependent effects of heat shock analyzed using western blot revealed increased HSP expression for up to 2[ ]h, followed by protein degradation after 4[ ]h. Hence, a heat shock damage duration of 4[ ]h was chosen for subsequent investigations. Calycosin administered post-heat shock demonstrated dose-dependent recovery of cell viability. Under heat shock conditions, calycosin prevented the apoptosis of H9c2 cells by upregulating HSPs, suppressing p-JNK, enhancing Bcl-2 activation, and inhibiting cleaved caspase 3. Calycosin also inhibited Fas/FasL expression and activated cell survival markers (p-PI3K, p-ERK, p-Akt), indicating their cytoprotective properties through PI3K/Akt activation and JNK inhibition. TUNEL staining and flow cytometry confirmed that calycosin reduced apoptosis. Moreover, calycosin reversed the inhibitory effects of quercetin on HSF1 and Hsp70 expression, illustrating its role in enhancing Hsp70 expression through HSF1 activation during heat shock. Immunofluorescence staining demonstrated HSF1 translocation to the nucleus following calycosin treatment, emphasizing its cytoprotective effects. In conclusion, calycosin exhibits pronounced protective effects against heat shock-induced damages by modulating HSP expression and regulating key signaling pathways to promote cell survival in H9c2 cells.

Fibroblast‐like synoviocytes accumulation, proliferation and activation, and the subsequent inflammatory mediators production play a key role in the progression of rheumatoid arthritis (RA). It is well established that Janus kinase 2/signal transducer and activator of transcription 3 (JAK2/STAT3) signaling triggers inflammation, and induces cytokine levels in RA. Ohwia caudata have long been used against many disorders. However, in RA, the effects of O. caudata have not been elucidated. In the current study, synoviocytes were used to evaluate the suppressive effects of O. caudate extract (OCE) on the pro‐inflammatory cytokines production. In vitro, the underlying mechanisms by which OCE inhibits inflammatory response through regulation of suppressors of cytokine signaling 3 (SOCS3) and JAK2/STAT3 expression in IL‐17A‐treated HIG‐82 synoviocytes were investigated. The results demonstrated that the proliferation of IL‐17A‐challenged cells were increased in comparison with non‐stimulated control cells. The synoviocyte proliferation was decreased significantly of OCE concentrations in dose dependent manner. The p‐JAK2, p‐STAT3, interleukin (IL)‐1β, and IL‐6 were reduced in IL‐17A‐challenged cells treated with OCE. Furthermore, AZD1480 (a JAK2‐specific inhibitor) or WP1066 (a STAT3‐specific inhibitor) affected the inflammatory mediators production in IL‐17A‐challenged synoviocytes, and OCE failed to mitigate the IL‐17A‐induced inflammatory mediators and SOCS3, acting as a feedback inhibitor of the JAK/STAT3 pathway, in the presence of SOCS3 siRNA, indicating that the beneficial effects of OCE on the regulation of inflammatory response homeostasis were dependent on SOCS3 and the JAK2/STAT3 signaling pathway. Our study also showed that SOCS3 was markedly activated by OCE in RA fibroblast‐like synoviocytes, thereby decreasing the JAK/STAT3 pathway, and the IL‐1β, and IL‐6 activation. Thus, O. caudate should be further investigated as a candidate anti‐inflammatory and anti‐arthritic agent.

Rheumatoid arthritis (RA) is an autoimmune and chronic inflammatory disease that results in joint destruction and disability in the adult population. RA is characterized by the accumulation and proliferation of fibroblast‐like synoviocytes. Many pro‐inflammatory mediators are associated with RA, such as interleukin (IL)‐1β, IL‐6, IL‐17, cyclooxygenase‐2 (COX‐2), and nuclear factor kappa B (NF‐κB). Furthermore, IL‐17 upregulates the production of other pro‐inflammatory mediators, including IL‐1β and IL‐6, and promotes the recruitment of neutrophils in RA.Artemisia argyi, a traditional Chinese herbal medicine, is used for the treatment of diseases associated with inflammation and microbial infections. In this study, synoviocytes (HIG‐82) were treated with varying doses ofA. argyiextract (AAE) following IL‐17A stimulation. Proliferation of the IL‐17A‐stimulated cells was increased compared to that of the non‐stimulated control cells. However, cell proliferation decreased significantly in a dose‐dependent manner following AAE treatment. Treatment of IL‐17A‐stimulated cells with AAE resulted in decreased levels of phosphorylated (p)‐NF‐κB, p‐IκB‐α, and COX‐2. Enzyme‐linked immunosorbent assay results showed that IL‐1β and IL‐6 levels were increased in the IL‐17A‐stimulated group but decreased in the AAE treatment group. Additionally, we found that AAE facilitated nuclear factor erythroid 2‐related factor 2 (Nrf2) expression and promoted its nuclear translocation, thereby inducing the expression of heme oxygenase‐1. Moreover, AAE did not attenuate IL‐17A‐induced inflammatory mediator production in the presence of ML385, an Nrf2‐specific inhibitor. These results suggest that the downregulation of expression of pro‐inflammatory cytokines and the transcription factor NF‐κB by AAE may be a potential therapeutic strategy for reducing inflammation associated with RA.

Diabetic neuropathy is a common complication of diabetes mellitus, posing a challenge in treatment. Previous studies have indicated the protective role of mesenchymal stem cells against several disorders. Although they can repair nerve injury, their key limitation is that they reduce viability under stress conditions. We recently observed that overactivation of the carboxyl terminus of heat shock protein 70 (Hsp70) interacting protein (CHIP) considerably rescued cell viability under hyperglycemic stress and played an essential role in promoting the beneficial effects of Wharton's jelly‐derived mesenchymal stem cells (WJMSCs). Thus, the present study was designed to unveil the protective effects of CHIP‐overexpressing WJMSCs against neurodegeneration using in vivo animal model based study. In this study, western blotting observed that CHIP‐overexpressing WJMSCs could rescue nerve damage observed in streptozotocin‐induced diabetic rats by activating the AMPKα/AKT and PGC1α/SIRT1 signaling pathway. In contrast, these signaling pathways were downregulated upon silencing CHIP. Furthermore, CHIP‐overexpressing WJMSCs inhibited inflammation induced in the brains of diabetic rats by suppressing the NF‐κB, its downstream iNOS and cytokines signaling nexus and enhancing the antioxidant enzyme system. Moreover, TUNEL assay demonstrated that CHIP carrying WJMSCs suppressed the apoptotic cell death induced in STZ‐induced diabetic group. Collectively, our findings suggests that CHIP‐overexpressing WJMSCs might exerts beneficial effects, which may be considered as a therapeutic strategy against diabetic neuropathy complications.

Angiostrongylus cantonensis causes a human central nervous system (CNS) infection characterized by eosinophilic meningitis or meningoencephalitis. Individuals infected with A. cantonensis exhibit unbalanced walking. The mechanism of extensive neurological impairments of hosts caused by A. cantonensis larvae remains unclear. Tight junction proteins (e.g., claudin-5 and zonula occludens-1) are the most important regulators of paracellular permeability and cellular adhesion. In a previous study, we found that increased matrix metalloproteinase-9 (MMP-9) activity may be associated with blood–CNS barrier disruption and/or the degeneration of Purkinje cells in eosinophilic meningitis caused by A. cantonensis. In the present study, the co-localization of MMP-9 and tight junction proteins on the degeneration of Purkinje cells was measured via confocal laser scanning immunofluorescence microscopy. The statistical evidence indicated that MMP-9 correlated between tight junction protein disruption and Purkinje cell degeneration at 20 days post-infection with A. cantonensis. In conclusion, Purkinje cell degeneration is highly correlated with tight junction protein disruption via the MMP-9 activation pathway.