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The discovery of transcription factor EB (TFEB) as a master regulator of the autophagy-lysosomal pathway (ALP) has triggered increasing numbers of studies that aim to explore the therapeutic potential of targeting TFEB to treat neurodegenerative disorders (NDs) such as Alzheimer's disease and Parkinson's disease. So far, the findings are exciting and promising. Here, we delineate the dysfunction of the TFEB-mediated ALP in NDs, and we summarize small molecules that have been identified as TFEB activators, along with their protective effects in NDs. We discuss the molecular mechanisms and targets, and the pros and cons of these TFEB activators from the perspective of drug development. Specific and potent small-molecule TFEB activators with ideal brain bioavailability could provide a method for treating NDs.

Lemairamin (also known as wgx-50), is isolated from the pericarps of the Zanthoxylum plants. As an agonist of α7 nicotinic acetylcholine receptors (α7nAChRs), it can reduce neuroinflammation in Alzheimer's disease. This study evaluated its antinociceptive effects in pain hypersensitivity and explored the underlying mechanisms. The data showed that subcutaneous lemairamin injection dose-dependently inhibited formalin-induced tonic pain but not acute nociception in mice and rats, while intrathecal lemairamin injection also dose-dependently produced mechanical antiallodynia in the ipsilateral hindpaws of neuropathic and bone cancer pain rats without affecting mechanical thresholds in the contralateral hindpaws. Multiple bi-daily lemairamin injections for 7 days did not induce mechanical antiallodynic tolerance in neuropathic rats. Moreover, the antinociceptive effects of lemairamin in formalin-induced tonic pain and mechanical antiallodynia in neuropathic pain were suppressed by the α7nAChR antagonist methyllycaconitine. In an α7nAChR antagonist-reversible manner, intrathecal lemairamin also stimulated spinal expression of IL-10 and β-endorphin, while lemairamin treatment induced IL-10 and β-endorphin expression in primary spinal microglial cells. In addition, intrathecal injection of a microglial activation inhibitor minocycline, anti-IL-10 antibody, anti-β-endorphin antiserum or μ-opioid receptor-preferred antagonist naloxone was all able to block lemairamin-induced mechanical antiallodynia in neuropathic pain. These data demonstrated that lemairamin could produce antinociception in pain hypersensitivity through the spinal IL-10/β-endorphin pathway following α7nAChR activation.

Alzheimer's disease (AD) is the most common age-related neurodegenerative disorder. Amyloid-β (Aβ) and hyper-phosphorylated tau accumulation are accountable for the progressive neuronal loss and cognitive impairments usually observed in AD. Currently, medications for AD offer moderate symptomatic relief but fail to cure the disease; hence development of effective and safe drugs is urgently needed for AD treatment. In this study, we investigated a Chinese medicine (CM) formulation named NeuroDefend (ND), for reducing amyloid β (Aβ) and tau pathology in transgenic AD mice models. Regular oral administration of ND improved cognitive function and memory in 3XTg-AD and 5XFAD mice. In addition, ND reduced beta-amyloid precursor protein (APP), APP C-terminal fragments (CTF-β/α), Aβ and 4G8 positive Aβ burden in 3XTg-AD and 5XFAD mice. Furthermore, ND efficiently reduced the levels of insoluble phospho-tau protein aggregates and AT8 positive phospho tau neuron load in 3XTg-AD mice. Hence, ND could be a promising candidate for the treatment of AD in humans. Keywords: Alzheimer's disease, Aβ-plaque, Neurofibrillary tangles, Chinese medicine, NeuroDefend

Graphical abstract, Highlights • Chitosan elicitation was conducted for flavonoid enhancement in hairy root cultures. • Chitosan elicitation gave a 7.08-fold increase in flavonoid yield over control. • Chalcone synthase and flavonoid 3′-hydroxylase might be two crucial genes. • Chitosan elicitation can facilitate the commercialization of plant in vitro cultures., Elicitation for phytochemical enhancement via cost-effective elicitors can overcome the limitation of commercial application faced by plant cell and organ culture technology. Chitosan is a natural, low-cost, and nontoxic elicitor that can trigger plant defense responses with the concomitant enhancement in phytochemical biosynthesis. In this work, the elicitation of Isatis tinctoria L. hairy root cultures by chitosan was conducted to enhance the production of pharmacologically active flavonoids. In comparison with control (2.31 ± 0.29 mg/g DW), a 7.08-fold enhancement of total flavonoids (16.35 ± 0.88 mg/g DW) was achieved in 24 day-old I. tinctoria hairy root cultures elicited by 150 mg/L chitosan for 36 h. Interestingly, the multiple hydroxyl-substituted flavonoids (rutin, quercetin, isorhamnetin, and isoliquiritigenin) were noticed to increase significantly in chitosan-elicited I. tinctoria hairy root cultures. Moreover, the transcription of associated genes involved in flavonoid biosynthesis pathway was significantly up-regulated underlying chitosan elicitation, among which chalcone synthase and flavonoid 3′-hydroxylase might play an important role in flavonoid enhancement. Additionally, extracts from chitosan-elicited I. tinctoria hairy root cultures exhibited higher antioxidant activities with lower IC50 values as compared with control. Overall, a cost-effective strategy via the simple chitosan elicitation is provided here to enhance the production of high-added value flavonoids in I. tinctoria hairy root cultures, which paves the way toward the successful commercialization of this in vitro culture system in the future.

Dan Li,1,* Ai-li Wang,2,* Yan-fen Gu,1 Qin Liu,3 Xiao-min Chen,4 Zi-ying Wang,5 Hui-ren Zhuang,1 Miao Du,6 Chi Chen,7 Hai-ping Yu1 1Department of Nursing, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 2Department of Pediatric Clinics, Shanghai United Family Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China; 3Department of Nursing, Shanghai SIPO Polytechnic, Shanghai, People’s Republic of China; 4Department of Finance, Shanghai University of Finance and Economics, Shanghai, People’s Republic of China; 5Department of Nursing, Shanghai Proton and Heavy Ion Center, Shanghai, People’s Republic of China; 6Department of Basic Nursing, School of Nursing and Health Management, Shanghai University of Medicine & Health Sciences, Shanghai, People’s Republic of China; 7Department of Teaching and Training, Shanghai East Hospital, Tongji University School of Medicine, Shanghai, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hai-ping YuDepartment of Nursing, Shanghai East Hospital, Tongji University School of Medicine, No.150 Jimo Road, Pudong New District, Shanghai, People’s Republic of ChinaTel +86 13501868164Email pingping670@sina.comChi ChenDepartment of Teaching and Training, Shanghai East Hospital, Tongji University School of Medicine, No.150 Jimo Road, Pudong New District, Shanghai, People’s Republic of ChinaTel +86 18930935171Email chichen2003@163.comObjective: Effective teamwork can provide safe and effective care in various medical systems. Thus, there is increasing recognition of the value of interprofessional collaborative practice. The Attitudes Toward Interprofessional Health Care Teams Scale (ATIHCTS) has been applied to a wide variety of health professions for evaluating attitudes toward health care teams. The ATIHCTS has been widely used internationally, but no Chinese version has been developed. The aim of this study was to adapt a Chinese version of the ATIHCTS among Chinese health care professionals and to test its validity.Methods: The English version of the ATIHCTS was translated into Chinese, back-translated, and modified for cultural adaptation according to Brislin’s guideline. A total of 306 health professionals in a Shanghai tertiary hospital were investigated using the Chinese version of the ATIHCTS to test its validity.Results: The Chinese version of the ATIHCTS was adjusted based on expert review and pilot testing. According to expert opinions, the text that did not conform to the Chinese language habits and the Chinese medical environment was adjusted. A total of five adjustments were made. After the pilot testing, minor corrections were made to improve the sentence structure of the scale instructions to make it easier to understand. Factor analysis was subsequently conducted with 306 respondents. The Chinese version of the ATIHCTS had 14 items. Exploratory factor analysis extracted two common factors, quality of care and time constraints, with the cumulative variance contribution rate reaching 70.011% and the load value of each entry on its common factor > 0.4. In addition, for scale confirmatory factor analysis (CFA), the chi-square/degrees of freedom ratio (X2/df) was 1.46, the normed fit index (NFI) was 0.97, the Tucker-Lewis index (TLI) was 0.99, the incremental fit index (IFI) was 0.99, the comparative fit index (CFI) was 0.99, and the root mean square error of approximation (RMSEA) was 0.04. The fitting values all met the judgment criteria, and the scale had good structural validity. Cronbach’s α of the Chinese version of the ATIHCTS was 0.861, and the Cronbach’s α values of each factor were 0.949 and 0.838, respectively. The split-half reliability was 0.644, and the Guttman split-half coefficients of each factor were 0.904 and 0.779, respectively.Conclusion: The Chinese version of the ATIHCTS has good validity. It is a valuable tool for evaluating attitudes toward interprofessional health care teams among the health care professionals in China.Keywords: interprofessional health care teams, attitudes, reliability, validity

Fibrosis is the final stage of the development of chronic inflammation. It is characterized by excessive deposition of the extracellular matrix, leading to tissue structure damage and organ dysfunction, which is a serious threat to human health and life. However, the molecular mechanism of fibrosis is still unclear. Inflammasome is a molecular complex of proteins that has been becoming a key innate sensor for host immunity and is involved in pyroptosis, pathogen infection, metabolic syndrome, cellular stress, and tumor metastasis. Inflammasome signaling and downstream cytokine responses mediated by the inflammasome have been found to play an important role in fibrosis. The inflammasome regulates the secretion of IL-1β and IL-18, which are both critical for the process of fibrosis. Recently, researches on the function of inflammasome have attracted extensive attention, and data derived from these researches have increased our understanding of the effects and regulation of inflammasome during fibrosis. In this review, we emphasize the growing evidence for both indirect and direct effects of inflammasomes in triggering fibrosis as well as potential novel targets for antifibrotic therapies.

D‐Amino acid oxidase (DAAO) specifically catalyzes the oxidative deamination of neutral and polar D‐amino acids and finally yields byproducts of hydrogen peroxide. Our previous work demonstrated that the spinal astroglial DAAO/hydrogen peroxide (H2O2) pathway was involved in the process of pain and morphine antinociceptive tolerance. This study aimed to report mouse strain specificity of DAAO inhibitors on antinociception and explore its possible mechanism. DAAO inhibitors benzoic acid, CBIO, and SUN significantly inhibited formalin‐induced tonic pain in Balb/c and Swiss mice, but had no antinociceptive effect in C57 mice. In contrast, morphine and gabapentin inhibited formalin‐induced tonic pain by the same degrees among Swiss, Balb/c and C57 mice. Therefore, mouse strain difference in antinociceptive effects was DAAO inhibitors specific. In addition, intrathecal injection of D‐serine greatly increased spinal H2O2 levels by 80.0% and 56.9% in Swiss and Balb/c mice respectively, but reduced spinal H2O2 levels by 29.0% in C57 mice. However, there was no remarkable difference in spinal DAAO activities among Swiss, Balb/c and C57 mice. The spinal expression of glutathione (GSH) and glutathione peroxidase (GPx) activity in C57 mice were significantly higher than Swiss and Balb/c mice. Furthermore, the specific GPx inhibitor D‐penicillamine distinctly restored SUN antinociception in C57 mice. Our results reported that DAAO inhibitors produced antinociception in a strain‐dependent manner in mice and the strain specificity might be associated with the difference in spinal GSH and GPx activity., Effects of DAAO inhibitors (CBIO, benzoic acid and SUN) were compared between Swiss, Balb/c and C57 mice in formalin test. The results showed that the DAAO inhibitors significantly inhibited formalin‐induced tonic pain in Balb/c and Swiss mice, but had no effect in C57 mice.

Neurodegenerative diseases (NDs) are common chronic diseases related to progressive damage of the nervous system. Globally, the number of people with an ND is dramatically increasing consistent with the fast aging of society and one of the common features of NDs is the abnormal aggregation of diverse proteins. Autophagy is the main process by which misfolded proteins and damaged organelles are removed from cells. It has been found that the impairment of autophagy is associated with many NDs, suggesting that autophagy has a vital role in the neurodegeneration process. Recently, more and more studies have reported that autophagy inducers display a protective role in different ND experimental models, suggesting that enhancement of autophagy could be a potential therapy for NDs. In this review, the evidence for beneficial effects of traditional Chinese medicine (TCM) regulate autophagy in the models of Alzheimer's disease (AD), Parkinson's disease (PD), and other NDs are presented and common autophagy-related mechanisms are identified. The results demonstrate that TCM which regulate autophagy are potential therapeutic candidates for ND treatment.

In our previous study, we reported a high temperature adapted strain (HTAS) of the predatory mite Neoseiulus barkeri was artificially selected via a long-term heat acclimation (35°C) and frequent heat hardenings. To understand the molecular basis of heat acclimation, 'omics' analyses were performed to compare the differences between HTAS female adults to conventional strain (CS) at transcriptional and translational levels. We obtained a total of 5,374 differentially expressed genes and 500 differentially expressed proteins. Among them, 119 transcripts had concurrent transcription and translation profiles. It's conserved that some processes, such as high expression of heat shock protein (HSP) genes, involved in heat tolerance of transcriptome analyses, while many protective enzymes including glutathione S-transferase, superoxide dismutase, peroxidase, and cytochrome P450 displayed down-regulated expression. KEGG analysis mapped 4,979 and 348 differentially expressed genes and proteins, to 299 and 253 pathways, respectively. The mitogen-activated protein kinases (MAPK) signaling pathway may provide new insights for the investigation of the molecular mechanisms of heat tolerance. Correlation enriched pathways indicated that there were four pathways associated with heat acclimation involving in energy metabolism and immunity. In addition, the expression patterns of ten randomly selected genes including HSP were consistent with the transcriptome results obtained through quantitative real-time PCR. Comparisons between transcriptome and proteome results indicated the upregulation of HSPs and genes participated in ATP production, immunity and energy metabolism process. A majority of antioxidant-related genes and detoxication-related genes were down-regulated suggesting a fitness cost of heat acclimation. Our results demonstrated that heat tolerance during a long-time acclimation of N. barkeri is a fairly complicated process of physiological regulations. These findings also contribute to a better understanding of the mechanisms of thermal responses of phytoseiid mites which could provide useful information for biological control through natural enemies.

The autophagy-lysosome pathway (ALP) is a primary means by which damaged organelles and long-lived proteins are removed from cells and their components recycled. Impairment of the ALP has been found to be linked to the pathogenesis of Parkinson's disease (PD), a chronic neurodegenerative disorder characterized by the accumulation of protein aggregates and loss of dopaminergic neurons in the midbrain. In recent years, some active compounds derived from plants have been found to regulate the ALP and to exert neuroprotective effects in experimental models of PD, raising the possibility that autophagy enhancement may be an effective therapeutic strategy in PD treatment. In this review, we summarize recent findings of natural products that enhance ALP and thereby protect against PD. Research articles were retrieved from PubMed using relevant keywords in combination. Papers related to the topic were identified, and then the reliability of the experiments was assessed in terms of methodology. The results suggest that targeting the ALP with natural products is a promising strategy for PD treatment. However, risk of bias exists in some studies due to the defective methodology. Rigorous experimental design following the guidelines of autophagy assays, molecular target identification and in vivo efficacy evaluation is critical for the development of ALP enhancers for PD treatment in future studies. Copyright © 2017 John Wiley & Sons, Ltd.

Chitosan, behaving as a potent biotic elicitor, can induce plant defense response with the consequent enhancement in phytoalexin accumulation. Accordingly, chitosan elicitation was conducted to promote the production of two phytoalexins, i.e. formononetin and calycosin (also known as health-promoting isoflavones), in Astragalus membranaceus hairy root cultures (AMHRCs). Compared with control, 12.45- and 6.17-fold increases in the yields of formononetin (764.19 ± 50.81 μg/g DW) and calycosin (611.53 ± 42.22 μg/g DW) were obtained in 34 day-old AMHRCs treated by 100 mg/L of chitosan for 24 h, respectively. Moreover, chitosan elicitation could cause oxidative burst that would induce the expression of genes (MPK3 and MPK6) related to mitogen-activated protein kinase signaling (MAPK) cascades, which contributed to the transcriptional activation of pathogenesis-related genes (β-1,3-glucanase, Chitinase, and PR-1) and eight biosynthesis genes involved in the calycosin and formononetin pathway. Overall, the findings in this work not only highlight a feasible chitosan elicitation practice to enhance the in vitro production of two bioactive isoflavones for nutraceutical and food applications, but also contribute to understanding the phytoalexin biosynthesis in response to chitosan elicitation.

Background and purpose d-Amino acid oxidase (DAAO) is a flavine adenine dinucleotide-containing flavoenzyme and specifically catalyses oxidative deamination of d-amino acids. This study aimed to explore the association between increased cerebral DAAO expression or enzymic activity and the development of cerebral ischaemia. Experimental approach A mouse model of transient (90 min) middle cerebral artery occlusion (MCAO) was established, and western blotting, enzymic activity assay, and fluorescent immunostaining techniques were used. Key results The expression and enzymic activity of DAAO increased over time in the cortical peri-infarct area of the mice subjected to transient MCAO. The DAAO was specifically expressed in astrocytes, and its double immunostaining with the astrocytic intracellular marker, glial fibrillary acidic protein, in the cortical peri-infarct area was up-regulated following ischaemic insult, with peak increase on Day 5 after MCAO. Single intravenous injection of the specific and potent DAAO inhibitor Compound SUN reduced the cerebral DAAO enzymic activity and attenuated neuronal infarction and neurobehavioural deficits with optimal improvement apparent immediately after the MCAO procedure. The neuroprotective effect was dose dependent, with ED50 values of 3.9-4.5 mg·kg-1 . Intracerebroventricular injection of the DAAO gene silencer siRNA/DAAO significantly reduced cerebral DAAO expression and attenuated MCAO-induced neuronal infarction and behavioural deficits. Conclusions and implications Our results, for the first time, demonstrated that increased cerebral astrocytic DAAO expression and enzymic activity were causally associated with the development of neuronal destruction following ischaemic insults, suggesting that targeting cerebral DAAO could be a potential approach for treatment of neurological conditions following cerebral ischaemia.

Ethnopharmacological relevance Immunomodulation has become a crucial modality for cancer treatment. Chinese Herbal Medicines (CHMs) are expected as adjuvant therapy for immunomodulation against cancer, but face the key challenge of poor scientific evidence. Changes of natural killer (NK) cells on numbers and/or cytotoxicity are a novel respect to evaluate the immunomodulation of CHMs. Aim of the study The purpose of this review is to investigate the immunomodulation of Chinese Herbal Medicines (CHMs) on NK cell populations for cancer therapy. Materials and methods A systematic review was conducted and outside mainstream electronic databases were screened for potential reference articles. This review tried to report and critically analyzed all the correlative studies, especially these clinical trials (3 CHM extracts and 11 CHM formulas). Results Evidence-based functions of CHMs against cancer could be summarized as: (1) enhancement of NK cells activity or relative percentage; (2) prevention of tumor growth and metastasis; (3) relief on side-effects or complications of therapeutic strategies (i.e. chemotherapy, radiotherapy and resection). Briefly, most of cellular studies and two thirds animal studies were based on the extract or components of single herbs, whilst most of clinical trials were keen on formula or prescription of CHMs. The main components of CHMs were demonstrated active on promoting the cytotoxicity of NK cells, including Angelica sinensis, Ganoderma lucidum, Panax ginseng, Radix Astragali, Lentinus edodes, etc. Conclusions This comprehensive review demonstrated NK cells activity was positively associated with quality of life but not survival benefit of cancer patients. Thus exploring the roles of NK cells in adjuvant therapy against cancer is confirmed to be beneficial to explore the underlying relationship between immunomodulation and quality of life.

Neurodegenerative diseases (NDs), including Alzheimer’s disease (AD) and Parkinson’s disease (PD), threaten the health of an ever-growing number of older people worldwide; so far, there are no effective cures. Significant efforts have been devoted to developing new drugs for NDs in recent years, and some small molecules have been shown to be promising in preclinical studies. However, the major challenge for brain-targeting drugs is how to efficiently deliver the drugs across the blood–brain barrier (BBB) to desired targets. To address this issue, liposomal delivery systems have proved to be ideal carriers for neuroprotective small molecules. Here, we summarize recent advances in the brain-targeting liposomal delivery of small hydrophobic molecules (SHMs) and propose strategies for developing liposomal SHMs as disease-modifying neurotherapeutics for NDs.

Hippocampal neurogenesis plays a critical role in the formation of new neurons during learning and memory development. Attenuation of neurogenesis in the brain is one of the primary causes of dementia in Alzheimer’s disease (AD), and, conversely, modulating the process of hippocampal neurogenesis benefit patients with AD. Traditional Chinese medicine (TCM), particularly herbal medicine, has been in use for thousands of years in Asia and many regions of the world for the treatment of cancer, cardiovascular diseases and neurodegenerative diseases. In this review, we summarize the role of neurotrophic factors, signal transducing factors, epigenetic modulators and neurotransmitters in neurogenesis, and we also discuss the functions of several Chinese herbs and their active molecules in activating multiple pathways involved in neurogenesis. TCM herbs target pathways such as Notch, Wnt, Sonic Hedgehog and receptor tyrosine kinase pathway, leading to activation of a signaling cascade that ultimately enhances the transcription of several important genes necessary for neurogenesis. Given these pathway activating effects, the use of TCM herbs could be an effective therapeutic strategy for the treatment of AD.

Two new species of the feather mite genus Analloptes Trouessart, 1885 (Xolalgidae: Ingrassiinae) are described from birds in China: Analloptes turnicis Mu and Wang sp. nov. ex barred buttonquail, Turnix suscitator (Gmelin, 1789) (Charadriiformes: Turnicidae) from Guizhou; and A. qujingensis Su and Wang sp. nov. ex red-billed chough, Pyrrhocorax pyrrhocorax (Linnaeus, 1758) (Passeriformes: Corvidae) from Yunnan. Two previously known species are redescribed based on the material from their type hosts collected from China: Analloptes megnini Trouessart, 1885 ex water rail, Rallus aquaticus (Linnaeus, 1758) (Gruiformes: Rallidae) from Yunnan, and Dubininia melopsittaci Atyeo and Gaud, 1987 ex budgerigar, Melopsittacus undulatus (Shaw, 1805) (Psittaciformes: Psittaculidae) from Guizhou.