Hericium erinaceus, an edible mushroom, has been demonstrated to potentiate the effects of numerous biological activities. The aim of this study was to investigate whether H. erinaceus mycelium could act as an anti-inflammatory agent to bring about neuroprotection using a model of global ischemic stroke and the mechanisms involved. Rats were treated with H. erinaceus mycelium and its isolated diterpenoid derivative, erinacine A, after ischemia reperfusion brain injuries caused by the occlusion of the two common carotid arteries. The production of inflammatory cytokines in serum and the infracted volume of the brain were measured. The proteins from the stroke animal model (SAM) were evaluated to determine the effect of H. erinaceus mycelium. H. erinaceus mycelium reduced the total infarcted volumes by 22% and 44% at a concentration of 50 and 300 mg/kg, respectively, compared to the SAM group. The levels of acute inflammatory cytokines, including interleukin-1β, interleukin-6 and tumor necrosis factor á, were all reduced by erinacine A. Levels of nitrotyrosine-containing proteins, phosphorylation of p38 MAPK and CCAAT enhancer-binding protein (C/EBP) and homologous protein (CHOP) expression were attenuated by erinacine A. Moreover, the modulation of ischemia injury factors present in the SAM model by erinacine A seemed to result in the suppression of reactive nitrogen species and the downregulation of inducible NO synthase (iNOS), p38 MAPK and CHOP. These findings confirm the nerve-growth properties of Hericium erinaceus mycelium, which include the prevention of ischemic injury to neurons; this protective effect seems to be involved in the in vivo activity of iNOS, p38 MAPK and CHOP.

Toll-like receptors (TLRs) not only form an important part of the innate immune system but also serve to activate the adaptive immune system in response to cancer. Real-time PCR; immunohistochemical stain and Western blotting analyses were performed to clarify molecular alterations in colorectal cancer (CRC) patients. We identified Toll-like receptor 1 (TLR1), TLR2, TLR4 and TLR8 gene expression levels and downstream gene, i.e., interleukin-6 (IL-6), IL-8, interferon-α (IFN-α) and myeloid differentiation primary-response protein-88 (MyD88), expression levels in CRC patients and in cancer cell lines. CRC tissues have higher TLR1, TLR2, TLR4, TLR8, IL-6 and IL-8 gene expression levels than do the normal colon mucosa (p < 0.05). TLR2 expression varied in different cell types (mucosa and lymphocytes). There was no difference in the MyD88 and IFN-α gene expression levels between cancerous and normal colon mucosa. CRC patients had higher levels of IL-6 (p = 0.002) and IL-8 (p = 0.038) expression than healthy volunteers did; and higher IL-6 and IL-8 expression was also found to signify a higher risk of recurrence. CL075 (3M002) treatments can reduce the production of IL-8 in different cancer cell lines. The signaling pathway of TLRs in cancer tissue is different from that in normal cells; and is MyD88-independent. Higher expression levels of TLR1, TLR2, TLR 4 and TLR 8 mRNA were related to upregulation inflammatory cytokines IL-6 and IL-8 gene expression in tissue and to the upregulation of IL-6 in blood. The concentration of IL-6 in serum can be used as an indicator of the possibility of CRC recurrence. Treatment with 3M002 can reduce IL-6 production in vitro and may prevent CRC recurrence. Our findings provide evidence that TLR1, TLR2, TLR4 and TLR8 gene expression induce downstream IL-6 and IL-8 gene expression; detection of these expression levels can serve as a CRC marker.

Background: Hericium erinaceus is an edible mushroom; its various pharmacological effects which have been investigated. This study aimed to demonstrate whether efficacy of oral administration of H. erinaceus mycelium (HEM) and its isolated diterpenoid derivative, erinacine A, can act as an anti-neuroinflammatory agent to bring about neuroprotection using an MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) mouse model of Parkinson’s disease, which results in motor disturbances, in addition to elucidating the mechanisms involved. Methods: Mice were treated with and without HEM or erinacine A, after MPTP injection for brain injuries by the degeneration of dopaminergic nigrostriatal neurons. The efficacy of oral administration of HEM improved MPTP-induced loss of tyrosine hydroxylase positive neurons and brain impairment in the substantia nigra pars compacta as measured by brain histological examination. Results: Treatment with HEM reduced MPTP-induced dopaminergic cell loss, apoptotic cell death induced by oxidative stress, as well as the level of glutathione, nitrotyrosine and 4-hydroxy-2-nonenal (4-HNE). Furthermore, HEM reversed MPTP-associated motor deficits, as revealed by the analysis of rotarod assessment. Our results demonstrated that erinacine A decreases the impairment of MPP-induced neuronal cell cytotoxicity and apoptosis, which were accompanied by ER stress-sustained activation of the IRE1α/TRAF2, JNK1/2 and p38 MAPK pathways, the expression of C/EBP homologous protein (CHOP), IKB-β and NF-κB, as well as Fas and Bax. Conclusion: These physiological and brain histological changes provide HEM neuron-protective insights into the progression of Parkinson’s disease, and this protective effect seems to exist both in vivo and in vitro.

Hericium erinaceus, a valuable pharmaceutical and edible mushroom, contains potent bioactive compounds such as H. erinaceus mycelium (HEM) and its derived ethanol extraction of erinacine A, which have been found to regulate physiological functions in our previous study. However, HEM or erinacine A with post-treatment regimens also shows effects on 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity, but its mechanisms remain unknown. By using annexin-V–fluorescein-isothiocyanate (FITC)/propidium iodide staining and a 2’,7’ –dichlorofluorescin diacetate (DCFDA) staining assay, the cell death, cell viability, and reactive oxygen species (ROS) of 1-methyl-4-phenylpyridinium (MMP⁺)-treated Neuro-2a (N2a) cells with or without erinacine A addition were measured, respectively. Furthermore, signaling molecules for regulating the p21/GADD45 cell death pathways and PAKalpha, p21 (RAC1) activated kinase 1 (PAK1) survival pathways were also detected in the cells treated with MPP⁺ and erinacine A by Western blots. In neurotoxic animal models of MPTP induction, the effects of HEM or erinacine A and its mechanism in vivo were determined by measuring the TH-positive cell numbers and the protein level of the substantia nigra through a brain histological examination. Our results demonstrated that post-treatment with erinacine A was capable of preventing the cytotoxicity of neuronal cells and the production of ROS in vitro and in vivo through the neuroprotective mechanism for erinacine A to rescue the neurotoxicity through the disruption of the IRE1α/TRAF2 interaction and the reduction of p21 and GADD45 expression. In addition, erinacine A treatment activated the conserved signaling pathways for neuronal survival via the phosphorylation of PAK1, AKT, LIM domain kinase 2 (LIMK2), extracellular signal-regulated kinases (ERK), and Cofilin. Similar changes in the signal molecules also were found in the substantia nigra of the MPTP, which caused TH+ neuron damage after being treated with erinacine A in the post-treatment regimens in a dose-dependent manner. Taken together, our data indicated a novel mechanism for post-treatment with erinacine A to protect from neurotoxicity through regulating neuronal survival and cell death pathways.

Purpose Delayed post-hemorrhoidectomy bleeding (DPHB) is a rare but serious complication. We investigated the incidence and risk factors of DPHB in patients undergoing hemorrhoidectomy using the LigaSure device or the Ferguson procedure. Methods This retrospective study included 382 consecutive patients with symptomatic grades II to IV hemorrhoids who received either LigaSure (184 patients) or Ferguson (198 patients) hemorrhoidectomy procedures. Thirty-two patients who experienced DPHB after discharge were followed up. Results Significantly fewer Ferguson group patients had DPHB compared to the LigaSure group (5.1% vs. 11.9%; P = 0.015). In the overall population, the risk of DPHB was higher in (1) males compared to that of females (OR = 3.39; 95% CI 1.50–7.69, P = 0.003); (2) in the LigaSure group compared to the Ferguson group (OR = 2.77; 95% CI 1.23–6.24, P = 0.01); and (3) in patients with constipation (OR = 6.59; 95% CI 2.73–15.89, P < 0.0001). Males in the LigaSure group had a significantly higher rate of delayed bleeding than those in the Ferguson group (20% vs. 5.8%, P = 0.004); no significant differences were found in females (4.9% vs. 4.5%, P = 0.878). Subgroup analysis showed that in males, risk of DPHB increased significantly with postoperative constipation (OR = 4.73, 95% CI 1.45–15.43, P = 0.010) and the LigaSure procedure (OR = 3.99, 95% CI 1.37–11.62, P = 0.011). In females, the risk of DPHB was significantly associated with postoperative constipation (OR = 8.80, 95% CI 2.24–34.54, P = 0.002). Conclusions The LigaSure procedure and constipation are independent risk factors for DPHB in patients undergoing hemorrhoidectomy and can be used as predictors of outcome.

The red blood cell distribution width (RDW) is a simple and widely available parameter obtained from a complete blood cell count test and is usually used in the analysis of anemia. Recently, studies have discovered the association between RDW and the host inflammatory response of cancer patients. We aimed to determine the prognostic value of RDW in colorectal cancer (CRC) patients. 5315 total patients with stage I-II CRC from the Chang Gung Memorial Hospital between 2001 and 2018 were enrolled. The study cohort was divided into two groups using RDW = 13.8 as the cutoff value as determined by receiver operating curve. High RDW had worse overall survival (OS), disease-free survival (DFS), and cancer-specific survival (CSS), and was also independently related to older age, more advanced tumor stage, lower albumin level, lower hemoglobin level, and more co-morbidities including diabetes, hypertension, and chronic kidney disease. We performed a propensity-score matched analysis to balance the heterogeneity between the two groups and to reduce the influence of confounding factors that may have compromised the prognosis. High RDW remained a negative predictor of OS (HR = 1.49, 95% CI: 1.25–1.78), as well as DFS and CSS. In conclusion, this is the first report using propensity matching to demonstrate the relationship between RDW and the prognosis of early-stage CRC patients.