Acupoint Thread Embedding Combined With Wenshen Bugu Decoction for the Treatment of Aromatase Inhibitor-Associated Musculoskeletal Symptom Among Postmenopausal Breast Cancer Patients: Study Protocol of a Randomized Controlled Trial.

BACKGROUND: Aromatase inhibitors (AIs) are recommended as the preferred therapy for postmenopausal women with hormone receptor-positive (HR+) breast cancer. As a result, aromatase inhibitor-associated musculoskeletal symptom (AIMSS) have become a major problem leading to therapy discontinuation and decreased quality of life in patients receiving adjuvant AIs treatment. Multiple therapies have been attempted, but have yielded limited clinical results. This study will be performed to determine whether acupoint thread embedding (ATE) combined with Wenshen Bugu Decoction can effectively treat AIMSS, so as to improve the AIs medication compliance of postmenopausal breast cancer patients. METHODS: This study will utilize a randomized, 2 parallel groups controlled trial design. A total of 128 eligible postmenopausal breast cancer women with AIMSS will be randomized to receive a 12-week treatment with Wenshen Bugu Decoction alone (control group) or in combination with ATE (treatment group) in a 1:1 ratio. The primary outcome will be the 12 week Brief Pain Inventory Worst Pain (BPI-WP) score. The secondary outcome measures will include response rate, Brief Pain Inventory-Short Form (BFI-SF), Western Ontario and McMaster Universities Osteoarthritis Index (WOMAC), Functional Assessment of Cancer Therapy-Endocrine Symptom (FACT-ES), Functional Assessment of Cancer Therapy-Breast (FACT-B), bone marrow density (BMD), blood markers of bone metabolite, Morisky medication adherence scale-8 (MMAS-8), credibility and expectancy, and survival outcomes. DISCUSSION: This trial may provide clinical evidence that ATE combined with Wenshen Bugu Decoction can be beneficial for treating AIMSS among postmenopausal breast cancer survivors. Our findings will be helpful to enhance the quality of life and reduce the occurrence of AIs withdrawal.

[A new sesquiterpene lactone from biological transformation of Hericium erinaceus and Artemisiae Annuae Herba].

This study aimed to investigate the chemical constituents from the biological transformation of Hericium erinaceus and Artemisiae Annuae Herba(HQ biological transformation). The chemical constituents of ethyl acetate fraction of 75% ethanol extract in HQ biological transformation were separated and purified by silica gel and Sephadex LH-20 gel column chromatographies together with semi-preparative high performance liquid chromatography(HPLC). Their structures were identified by physicochemical properties, spectroscopic analysis, as well as comparisons with the data reported in literature. Nine compounds were isolated and identified as 2α-hydroxydeoxyartemisinin(1), 6ß-hydroxy-stigmast-4,22-dien-3-one(2), 3ß,5α-dihydroxy-ergosta-7,22-dien-6-one(3), friedelin(4), dankasterone(5), ergosterol endoperoxide(6), 3ß-hydroxy-5,9-epoxy-(22E,24R)-ergosta-7,22-dien-6-one(7), 3α,5α,9α-trihydroxy-(22E,24R)-ergosta-7,22-dien-6-one(8), and stigmast-3-one(9). Compound 1 was a new sesquiterpene lactone named 2α-hydroxy-deoxyartemisinin. The activity against Helicobacter pylori(Hp) of compounds 1-9 in vitro was determined by Kirby-Bauer disk diffusion method. The screening results showed compounds 1, 2 and 5 had certain anti-Hp activity.

Cerebral Metabolism Related to Cognitive Impairments in Multiple System Atrophy.

Objective: We aimed to characterize the cognitive profiles in multiple system atrophy (MSA) and explore the cerebral metabolism related to the cognitive decline in MSA using 18F-fluorodeoxyglucose (18F-FDG) Positron Emission Tomography (PET). Methods: In this study, 105 MSA patients were included for cognitive assessment and 84 of them were enrolled for 18F-FDG PET analysis. The comprehensive neuropsychological tests covered five main domains including execution, attention, memory, language, and visuospatial function. The cognitive statuses were classified to MSA with normal cognition (MSA-NC) and MSA with cognitive impairment (MSA-CI), including dementia (MSA-D), and mild cognitive impairment (MSA-MCI). With 18F-FDG PET imaging, the cerebral metabolism differences among different cognitive statuses were analyzed using statistical parametric mapping and post-hoc analysis. Results: Among 84 MSA patients, 52 patients were found with MSA-CI, including 36 patients as MSA-MCI and 16 patients as MSA-D. In detail, the cognitive impairments were observed in all the five domains, primarily in attention, executive function and memory. In 18F-FDG PET imaging, MSA-D and MSA-MCI patients exhibited hypometabolism in left middle and superior frontal lobe compared with MSA-NC (p < 0.001). The normalized regional cerebral metabolic rate of glucose (rCMRglc) in left middle frontal lobe showed relative accuracy in discriminating MSA-CI and MSA-NC [areas under the curve (AUC) = 0.750; 95%CI = 0.6391-0.8609]. Conclusions: Cognitive impairments were not rare in MSA, and the hypometabolism in frontal lobe may contribute to such impairments.

Brain Metabolisms Involved in Self-Reported Quality of Mobility in Parkinson's Disease.

BACKGROUND: Objective motor ratings and subjective motor complaints are both widely used in Parkinson's disease (PD). However, the objective basis to the self-perceived mobility quality is still not well elucidated. PURPOSES: We aimed to figure out the relevancy between the UPDRS motor scores and PDQ39 mobility sub-scores, and further explore whether physician-assessed motor dysfunctions and patients-reported mobility deficits have some shared mechanisms. METHODS: 49 patients with PD who completed the PDQ39 scale were retrospectively included. The relevancy between mobility quality and UPDRS scores was assessed, as well as the related presynaptic dopaminergic binding (11C-CFT) and glucose metabolism (18F-FDG) in this dual-tracer PET imaging study. RESULTS: Modest correlation was found between UPDRS motor score and the PDQ39 mobility sub-score (r = 0.440, p = 0.002). No correlation was found between PDQ39 mobility SI and the dopaminergic lesions in putamen; however, the strict correlation was found with the UPDRS motor scores. In terms of global PD related pattern (PDRP) scores, the two motor scores both correlated strictly. In the further regional metabolism exploration, cerebellum correlated positively with PDQ39 mobility sub-scores, and the frontal and parietal regions mainly correlated negatively with the motor quality scores. CONCLUSION: UPDRS motor scores and PDQ39 mobility scores were only modestly correlated. The mechanisms involved under mobility quality were beyond dopaminergic deficiency, including motor related cerebellum hyper-metabolism and non-motor related frontal hypo-metabolism. Conclusively, the self-reported mobility experience may have the neurophysiological basis related to both motor and non-motor manifestations in PD.

Fasudil Promotes α-Synuclein Clearance in an AAV-Mediated α-Synuclein Rat Model of Parkinson's Disease by Autophagy Activation.

BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, but the disease-modifying therapies focusing on the core pathological changes are still unavailable. Rho-associated protein kinase (ROCK) has been suggested as a promising target for developing neuroprotective therapies in PD. OBJECTIVE: We aimed to explore the promotion of α-synuclein (α-syn) clearance in a rat model. METHODS: In a rat model induced by unilateral injection of adeno-associated virus of serotype 9 (AAV9) expressing A53T α-syn (AAV9-A53T-α-syn) into the right substantia nigra, we aimed to investigate whether Fasudil could promote α-syn clearance and thereby attenuate motor impairments and dopaminergic deficits. RESULTS: In our study, treatment with Fasudil (5 mg/kg rat weight/day) for 8 weeks significantly improved the motor deficits in the Cylinder and Rotarod tests. In the in vivo positron emission tomography imaging with the ligand 18F-dihydrotetrabenazine, Fasudil significantly enhanced the dopaminergic imaging in the injected striatum of the rat model (p < 0.05 vs. vehicle group, p < 0.01 vs. left striatum in Fasudil group). The following mechanistic study confirmed that Fasudil could promote the autophagic clearance of α-syn by Becline 1 and Akt/mTOR pathways. CONCLUSION: Our study suggested that Fasudil, the ROCK2 inhibitor, could attenuate the anatomical and behavioral lesions in the Parkinsonian rat model by autophagy activation. Our results identify Fasudil as a drug with high translational potential as disease-modifying treatment for PD and other synucleinopathies.

Chemical characterization of constituents from Polygonatum cyrtonema Hua and their cytotoxic and antioxidant evaluation.

Twenty-four compounds were isolated from the roots of Polygonatum cyrtonema Hua, including a new octopamine dimer, named trans-bis(N-feruloyl)octopamine (1). The structure was established on the basis of spectroscopic and chemical methods. All the extracts and compounds were evaluated for cytotoxic and antioxidant activities by using MTT and chemiluminescence assay. The extracts showed activity against MCF-7 and HepG-2 cell lines from IC50 0.30 to 1.01 mg mL-1. Compound 3 exhibited activity against HepG-2 cell lines with IC50 8.99 µM. Compound 7 exhibited activity against Hela cell lines with IC50 2.53 µM and BGC-823 cell lines with IC50 7.77 µM. Moreover, compound 7 showed antioxidant with IC50 12 µM compared to the positive control with IC50 77 µM. Compound 16 exhibited activity against HepG-2 cell lines with IC50 1.05 µM and MCF-7 cell lines with IC50 1.89 µM. These results indicated that this plant might be potential in natural medicine and healthy food.

Considerations before initiating therapy in Parkinsonism: basing on the quality of life.

OBJECTIVE: Improvement of quality-of-life (QoL) has been termed as a primary objective in initiating therapy in both Parkinson's disease (PD) and multiple system atrophy Parkinsonian subtype (MSA-P). We aimed to compare the determinants of life quality in drug naïve PD and MSA-P patients. METHODS: Eighty-six drug-naïve PD patients and thirty-five drug-naïve MSA-P patients were included to explore the determinants of QoL. Demographic information, motor deficits, and non-motor symptoms were included in the clinical assessment. RESULTS: Both motor and non-motor functions were more severely impaired in the drug-naïve MSA-P patients, with higher PDQ-39 scores indicating poorer QoL. Physical discomfort and stigma were the main affected sub-domains in PD, while mobility and activity of daily life were the main affected ones in MSA-P. BECK depressive scores and UPDRS-III scores were independent variables of PDQ-39 in MSA-P patients. Age, depression, disease stages and non-motor scores were independent variables of PDQ-39 in PD patients. INTERPRETATION: Drug-naïve MSA-P patients suffered from more severe motor and non-motor disability, as well as poorer QoL. Depression and non-motor symptoms were proved to be the most critical determinants for QoL in PD, while motor function was supposed to be the major determinant for MSA-P. When initiating therapy, physicians need to focus more on motor functions in drug-naïve MSA-P patients, but on depression in PD patients.

Roles of eNOS in atherosclerosis treatment.

BACKGROUND: Atherosclerosis (AS) is the main pathogeny of coronary heart disease, cerebral infarction and peripheral vascular disease. Endothelial dysfunction is one of the important pathogenesis of AS. As an important endothelium-derived relaxation factor, nitric oxide (NO) plays a role in cardiovascular protection and anti-AS function; but in the pathological state, endothelial nitric oxide synthase (eNOS) disorder causes an abnormal production of NO, which may damage endothelial function and trigger AS. This review summarized the research progresses in the treatment strategies for AS based on correcting the disordered eNOS/ NO signaling pathway. MAIN BODY: According to the topic, select the search terms 'atherosclerosis,' 'nitric oxide,' 'eNOS,' 'treatment,' 'management,' 'medication,' 'maintenance,' 'remission'. Using these terms, a structured literature search via multiple electronic databases was performed for the most recent trial evidence in recent years. We read and analyze these literatures carefully, classified these literatures according to their content, and then summarized and outlined the common main points in these classified literatures. Finally, literature data were organized to discuss these main points logically. We found that both aberrant expression and dysfunction of eNOS are closely related to AS development, and some new treatment strategies aimed at eNOS have been proposed, including upregulation of eNOS expression and inhibition of eNOS uncoupling. The former one is mainly related to inflammatory inhibition and protection of the PKB-eNOS signaling pathway; whereas the latter one is associated with the addition of the L-arginine substrate of eNOS, arginase inhibition, and the supplement of tetrahydrobiopterin, which can elevate no level. CONCLUSIONS: eNOS can be an important target for prevention and treatment of AS, and eNOS drugs may be another potent class of effective therapeutic treatment for AS following traditional lipid-lowering, anti-platelet, vasodilator drugs. But applying these experimental results to clinic treatment still requires further studies and development of biotechnology.

Regulating Cdc42 and Its Signaling Pathways in Cancer: Small Molecules and MicroRNA as New Treatment Candidates.

Despite great improvements in the diagnosis and treatment of neoplasms, metastatic disease is still the leading cause of death in cancer patients, with mortality rates still rising. Given this background, new ways to treat cancer will be important for development of improved cancer control strategies. Cdc42 is a member of the Rho GTPase family and plays an important role in cell-to-cell adhesion, formation of cytoskeletal structures, and cell cycle regulation. It thus influences cellular proliferation, transformation, and homeostasis, as well as the cellular migration and invasion processes underlying tumor formation. Cdc42 acts as a collection point for signal transduction and regulates multiple signaling pathways. Moreover, recent studies show that in most human cancers Cdc42 is abnormally expressed and promoting neoplastic growth and metastasis. Regarding possible new treatments for cancer, miRNA and small molecules targeting Cdc42 and related pathways have been recently found to be effective on cancer. In this review, we analyze the newly recognized regulation mechanisms for Cdc42 and Cdc42-related signal pathways, and particularly new treatments using small molecules and miRNAs to inhibit the abnormal overexpression of Cdc42 that may slow down the metastasis process, improve cancer therapy and lead to novel strategies for development of antineoplastic drugs.

Recent progress on the effects of microRNAs and natural products on tumor epithelial-mesenchymal transition.

Epithelial-mesenchymal transition (EMT) is a biological process of phenotypic transition of epithelial cells that can promote physiological development as well as tissue healing and repair. In recent years, cancer researchers have noted that EMT is closely related to the occurrence and development of tumors. When tumor cells undergo EMT, they can develop enhanced migration and local tissue invasion abilities, which can lead to metastatic growth. Nevertheless, two researches in NATURE deny its necessity in specific tumors and that is discussed in this review. The degree of EMT and the detection of EMT-associated marker molecules can also be used to judge the risk of metastasis and to evaluate patients' prognosis. MicroRNAs (miRNAs) are noncoding small RNAs, which can inhibit gene expression and protein translation through specific binding with the 3' untranslated region of mRNA. In this review, we summarize the miRNAs that are reported to influence EMT through transcription factors such as ZEB, SNAIL, and TWIST, as well as some natural products that regulate EMT in tumors. Moreover, mutual inhibition occurs between some transcription factors and miRNAs, and these effects appear to occur in a complex regulatory network. Thus, understanding the role of miRNAs in EMT and tumor growth may lead to new treatments for malignancies. Natural products can also be combined with conventional chemotherapy to enhance curative effects.

New isoindolinones from the fruiting bodies of Hericium erinaceum.

Hericium erinaceus is a well-known medicinal and edible mushroom, which is considered as a potential source to obtain antitumor candidates. In this work, five new isoindolinones, named erinaceolactams A-E (1-5), along with five known compounds (6-10), were isolated from 70% ethanol extract of the fruiting bodies of H. erinaceus. The structures of new compounds were validated by HRESIMS and 1D, 2D NMR. It's worth mentioning that there are two pairs of isomers included in the new compounds. Moreover, their cytotoxicity against metastatic human hepatocellular carcinoma cell lines SMMC-7221 and MHCC-97H were evaluated. The results showed that compounds 6 and 7 exhibited promising inhibitory potency against the growth of two cell lines.