Baicalein, a typical flavonoid compound, has neuroprotective properties in several neurological disorders. Autophagy plays a central role in maintaining the cellular homeostasis, and is involved in the pathogenesis of Parkinson's disease (PD). Recently, baicalein has been reported to induce autophagy. Therefore, the current study was designed to investigate whether baicalein could protect against rotenone-induced neurotoxicity via induction of autophagy both in SH-SY5Y cells and in a mouse model. A chronic PD mouse model was established by continuous intragastric administration of rotenone for 12 weeks. Baicalein was administrated from 7 to 12 week. Our results showed that baicalein prevented rotenone-induced behavioral deficits, dopaminergic neuronal loss, apoptosis and mitochondrial dysfunction. Furthermore, baicalein restored rotenone-impaired autophagy, and blocking the baicalein-induced autophagy using 3-methyladenine inhibited the neuroprotective effects of bacalein. Baicalein increased cell viability and restored mitochondrial function in SH-SY5Y cells. The beneficial effect of baicalein was abrogated by 3-methyladenine treatment. Furthermore, rapamycin increased autopahgy and reduced the rotenone-induced neurotoxicity in SH-SY5Y cells. Collectively, these results suggest that baicalein could prevent rotenone-induced neurotoxicity via restoring autophagy. Key words baicalein; neuroprotection; Parkinson's disease; autophagyParkinson's disease (PD) is a progressive neurodegenerative disorder characterized by bradykinesia, rigidity, resting tremor, and postural instability.1-3) The main pathological characteristic of PD is the progressive degeneration of dopaminergic neurons in the substantia nigra pars compacta, the loss of dopamine in the striatum, and the presence of intracytoplasmic inclusions in surviving neurons known as Lewy bodies.4) Several biochemical mechanisms related to the pathogenesis of PD include oxidative stress, mitochondrial dysfunction, protein aggregation and misfolding, apoptosis, excitotoxicity, and neuroinflammation.5,6) Currently, none of therapies has been convincingly shown to slow down or prevent the progression of PD, and additional effective treatments for this disease are urgently needed.Baicalein, a flavonoid, is derived from the root of the traditional Chinese herb Scutellariabaicalensis GEORGI. Baicalein has been reported to have neuroprotective effects in PD model through anti-inflammatory, anti-apoptosis, and anti-oxidative actions. In vitro, baicalein protected PC12 cells against 6-hydroxydopamine (6-OHDA)-or rotenone-induced neurotoxicity, 7,8) and ameliorated the 6-OHDA-induced SH-SY5Y cell apoptosis.9) In vivo, baicalein exerted neuroprotective effects in 6-OHDA-induced neurotoxicity in rats 9) and in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-induced neurotoxicity in mice.10) However, the exact mechanism of baicalein is poorly understood.Autophagy is a highly conservative cellular process by which cells degrade and recycle of bulk cytosolic proteins and dama...
Osteosarcoma is the most commonly diagnosed primary malignant bone tumor, with similar global incidence rate across childhood and adolescence. Patients with localized disease have a 5-year survival period of 80 %; however, the prognosis is poor in those with metastatic osteosarcoma. The origin of the primary tumor is most frequently the metaphyseal (actively growing) regions of the distal femur, proximal tibia, and proximal humerus, although the tumor can develop in any bone, and the most likely sites for metastasis are the lungs and bone. Ezrin is a member of the ezrin-radixin-moesin (ERM) family of proteins that functions as a cross-linker between the actin cytoskeleton and the plasma membrane, and ezrin also plays a positive role in maintaining cell shape and polarity and facilitates membrane-trafficking pathways, cell migration, cell signaling, growth regulation, and differentiation. There is strong evidence to suggest that ezrin is necessary for osteosarcoma metastasis. The objective of the current review is to summarize the know-how about metastatic progression in osteosarcoma, with a focus on ezrin. Despite the promise that preliminary studies on ezrin have shown, there is a great need to further analyze the role of ezrin in osteosarcoma metastasis and to determine its usefulness as a biomarker for the disease.
Background: Assessment of patient-reported outcomes (PRO) has become essential for evaluation of the burden of disease and of the benefits and side effects of therapy. Aims: Here, we compare parameters of QoL in patients with relapsed/ refractory multiple myeloma (RRMM) with an age-matched control population and evaluate the impact of relapse therapy with ixazomib, thalidomide and dexamethasone (IxaThalDex) followed by ixazomib maintenance therapy on several dimensions of QoL. Methods: PRO was assessed using the EORTC QLQ-C30 and the EO-RTC QLQ-MY20 instruments at baseline and at the beginning of each cycle of induction and maintenance therapy. Eighty-nine patients were enrolled and started on induction therapy receiving ixazomib ( 4mg [3 mg in pts ≥75 yrs], d 1,8,15), thalidomide (100 mg [50 mg in pts ≥75yrs] daily) and dexamethasone (40 mg [20 in pts ≥75yrs]/week) for 8 cycles and ixazomib maintenance therapy (4 mg d1, 8, 15) for 12 months. Score interpretation regarding what was considered a clinically meaningful difference was guided by recommendations by Cocks et al., JCO, 2010. Differences between baseline and end of induction therapy were analyzed in all 43 patients who completed all 8 cycles. 2.337 individuals aged 60-69 years of the general population served as controls (Nolte et al., Eu J Cancer, 2019). Differences were assessed by T test.
Immunogenic cell death (ICD) is a type of regulated cell death (RCD) triggered by various stresses that are involved in activating the immune system against cancer in immunocompetent hosts. However, no previous study has investigated the regulation of ICD-related gene pairs involved in hepatocellular carcinoma (HCC). A prognostic signature composed of 8 ICD-related gene pairs was generated that was capable of reliably separating patients with HCC into low-and high-risk subgroups with differing overall survival rates. Significant correlations were observed between risk score and surgical procedure, vascular tumor cell type, recurrence status, tumor status, and stages. The risk score was confirmed to be an independent prognostic factor for HCC and subsequently was employed to construct a prognostic nomogram. Low-risk patients were characterized by higher levels of immune cell infiltration, lower stromal and immune scores, higher tumor purity, higher expression of most immune checkpoints, and higher tumor mutational burden (TMB), revealing different levels of immunological functional pathways between different risk HCC patient cohorts. Furthermore, immunophenoscore (IPS) and Tumor Immune Dysfunction and Exclusion (TIDE) scores demonstrated that patients in the low-risk group are more likely to be sensitive to immunotherapy. In conclusion, the signature conducted by ICD-related gene pairs is a promising biomarker for the prediction of HCC patient outcomes and immunotherapeutic responses.
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