Acetylcholinesterase is regulated by exposure of ultraviolet B in skin keratinocytes: A potential inducer of cholinergic urticaria.

Cholinergic urticaria is a dermatological disease characterized by the presence of large patches of red skin and transient hives triggered by factors, such as exercise, sweating, and psychological tension. This skin problem is hypothesized to be attributed to a reduced expression of acetylcholinesterase (AChE), an enzyme responsible for hydrolyzing acetylcholine (ACh). Consequently, ACh is thought to the leak from sympathetic nerves to skin epidermis. The redundant ACh stimulates the mast cells to release histamine, triggering immune responses in skin. Here, the exposure of ultraviolet B in skin suppressed the expression of AChE in keratinocytes, both in in vivo and in vitro models. The decrease of the enzyme was resulted from a declined transcription of ACHE gene mediated by micro-RNAs, that is, miR-132 and miR-212. The levels of miR-132 and miR-212 were markedly induced by exposure to ultraviolet B, which subsequently suppressed the transcriptional rate of ACHE. In the presence of low level of AChE, the overflow ACh caused the pro-inflammatory responses in skin epidermis, including increased secretion of cytokines and COX-2. These findings suggest that ultraviolet B exposure is one of the factors contributing to cholinergic urticaria in skin.

MircoRNA-25-3p in skin precursor cell-induced Schwann cell-derived extracellular vesicles promotes axon regeneration by targeting Tgif1.

Nerve injury often leads to severe dysfunction because of the lack of axon regeneration in adult mammal. Intriguingly a series of extracellular vesicles (EVs) have the obvious ability to accelerate the nerve repair. However, the detailed molecular mechanisms to describe that EVs switch neuron from a transmitter to a regenerative state have not been elucidated. This study elucidated the microRNA (miRNA) expression profiles of two types of EVs that promote nerve regeneration. The functions of these miRNAs were screened in vitro. Among the 12 overlapping miRNAs, miR-25-3p was selected for further analysis as it markedly promoted axon regeneration both in vivo and in vitro. Furthermore, knockdown experiments confirmed that PTEN and Klf4, which are the major inhibitors of axon regeneration, were the direct targets of miR-25-3p in dorsal root ganglion (DRG) neurons. The utilization of luciferase reporter assays and functional tests provided evidence that miR-25-3p enhances axon regeneration by targeting Tgif1. Additionally, miR-25-3p upregulated the phosphorylation of Erk. Furthermore, Rapamycin modulated the expression of miR-25-3p in DRG neurons. Finally, the pro-axon regeneration effects of EVs were confirmed by overexpressing miR-25-3p and Tgif1 knockdown in the optic nerve crush model. Thus, the enrichment of miR-25-3p in EVs suggests that it regulates axon regeneration, proving a potential cell-free treatment strategy for nerve injury.

The extracts of Dracaena cochinchinensis stemwood suppress inflammatory response and phagocytosis in lipopolysaccharide-activated microglial cells.

BACKGROUND: Neuroinflammation is a pivotal process in the brain that contributes to the development of neurodegenerative diseases, such as Alzheimer's disease (AD). During neuroinflammation, the over-activation of microglial cells can drive the pathological processes underlying AD, including an increase in amyloid ß (Aß) production and accumulation, ultimately leading to neuronal and synaptic loss. Dracaena cochinchinensis (Lour.) S.C. Chen, also known as "Chan-daeng" in Thai, belongs to the Asparagaceae family. In Thai traditional medicine, it has been used as an antipyretic, pain reliever, and anti-inflammatory agent. However, the effects of D. cochinchinensis on neuroinflammation are yet to be determined. PURPOSE: We aimed to evaluate the anti-neuroinflammatory activities of D. cochinchinensis stemwood extract in activated microglia. METHODS: In this study, lipopolysaccharide (LPS), a potent pro-inflammatory stimulus, was used to activate microglial BV2 cells, as a cell model of neuroinflammation. Our investigation included several techniques, including qRT-PCR, ELISA, Western blotting, phagocytosis, and immunofluorescence staining, to examine the potential anti-inflammatory effects of D. cochinchinensis stemwood. RESULTS: D. cochinchinensis stemwood, named DCS, was extracted with ethanol and water. The extracts of DCS showed dose-dependent anti-inflammatory effects, markedly suppressing the LPS-mediated mRNA expression of pro-inflammatory factors, including IL-1ß, TNF-α, and iNOS, while increasing expression of the anti-inflammatory biomarker Arg1 in both BV2 microglia and RAW264.7 macrophages. DCS extracts also decreased the protein levels of IL-1ß, TNF-α, and iNOS. These findings were correlated with the suppression of phosphorylated proteins of p38, JNK, and Akt in the LPS-activated microglia. Moreover, DCS extracts significantly attenuated excessive phagocytosis of beads and Aß fibrils during the LPS-mediated microglial activation. CONCLUSION: Taken together, our results indicated that DCS extracts had anti-neuroinflammatory properties by suppressing the expression of pro-inflammatory factors, increasing the expression of the anti-inflammatory biomarker Arg1, and modulating excessive phagocytosis in activated microglia. These findings suggested that DCS extract could be a promising natural product for the treatment of neuroinflammatory and neurodegenerative diseases, like AD.

The role and mechanism of circ-BNC2 on the malignant progression of oral squamous cell carcinoma.

BACKGROUND: Circular RNAs (circRNAs) play a key part in the progression of oral squamous cell carcinoma (OSCC). However, the role of circ-BNC2 (circRNA ID hsa_circ_0086414) in OSCC progression is still unclear. METHODS: Plasmid transfection was used to induce overexpression of circ-BNC2. RNA expression of circ-BNC2, microRNA-142-3p (miR-142-3p) and GNAS complex locus (GNAS) was detected by quantitative real-time polymerase chain reaction. Protein expression was assessed by western blot assay or immunohistochemistry assay. Cell proliferation was investigated by 3-(4,5-dimethylthazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, colony formation assay and flow cytometry analysis. Cell migratory and invasive abilities and cell apoptosis were assessed by transwell assay and flow cytometry analysis, respectively. Oxidative stress was evaluated by superoxide dismutase activity detection assay, lipid peroxidation malondialdehyde assay and cellular reactive oxygen species assay. The binding relationship between miR-142-3p and circ-BNC2 or GNAS was proved by dual-luciferase reporter assay and RNA immunoprecipitation assay. The impacts of circ-BNC2 overexpression on tumor growth in vivo were unveiled by a xenograft mouse model assay. RESULTS: Circ-BNC2 expression was downregulated in OSCC tissues and cells when compared with adjacent healthy tissues and normal human oral keratinocytes. Circ-BNC2 overexpression repressed the proliferation, migration and invasion of OSCC cells but induced cell apoptosis and oxidative stress. Additionally, circ-BNC2 overexpression inhibited tumor growth in vivo. Furthermore, circ-BNC2 bound to miR-142-3p, and miR-142-3p targeted GNAS. MiR-142-3p mimic attenuated circ-BNC2 overexpression-mediated effects on the proliferation, migration, invasion, apoptosis and oxidative stress of OSCC cells. The regulation of miR-142-3p in OSCC cell tumor properties involved GNAS. Further, circ-BNC2 introduction promoted GNAS expression by inhibiting miR-142-3p. CONCLUSION: Circ-BNC2 suppressed OSCC malignant progression by upregulating GNAS expression in a miR-142-3p-dependent manner, which suggested that circ-BNC2 might be a novel target for OSCC therapy.

Disruption of RBMS3 suppresses PD-L1 and enhances antitumor immune activities and therapeutic effects of auranofin against triple-negative breast cancer.

Programmed cell death protein-1 (PD-1)/programmed cell death ligand-1 (PD-L1) interaction exerts a vital role in tumor-associated immune evasion. While strategies disrupting PD-1/PD-L1 axis have shown clinical benefits in various cancers, the limited response rate prompts us to investigate the complex mechanisms underlying the molecular regulation of PD-L1. Here, we identify the RNA binding protein RBMS3 as a crucial PD-L1 regulator in triple-negative breast cancer (TNBC). Correlation analysis shows that Rbms3 significantly correlates with immunosuppressive CD274, Rbms1, NT5E and ENTPD1. RBMS3 protein binds to CD274 mRNA specifically in TNBC cells to increase PD-L1 levels. Mechanistically, RBMS3 stabilizes CD274 mRNA by interacting with its 3'UTR, which represents as an intrinsic cancer cell mechanism for driving PL-D1 upregulation in TNBC. RBMS3 depletion not only destabilizes the mRNA stability and protein expression of PD-L1, but also suppresses the migratory abilities of TNBC MDA-MB-231 cells. Importantly, combination of RBMS3 ablation with auranofin (AUF), an FDA-approved thioredoxin reductase inhibitor, facilitates anti-tumor T-cell immunity in vivo and improves AUF-mediated anti-cancer effect. Taken together, our findings reveal RBMS3 as a key post-transcriptional regulator of PD-L1 and how they contribute to immune escape in TNBC, which could lead to novel combinatorial therapeutic strategies to enhance the efficacy of cancer immunotherapy.

Novel phenylpropanoids and isoflavone glycoside are isolated and identified from the carob pods (Ceratonia siliqua L.).

Two new phenylpropanoids (1 and 2) and one new isoflavone glycoside (3), along with nine known compounds (4 - 12), were isolated from the pod of Ceratonia siliqua L. Their chemical structures were elucidated based on extensive spectroscopic analyses (1 D and 2 D NMR, UV, IR, and HRESIMS) and compared with the literature data. In addition, all isolated compounds were evaluated in vitro for inhibitory activity against acetylcholinesterase (AChE). Compounds 4, 5, and 12 showed inhibitory activity against acetylcholinesterase (AChE) with IC50 values ranging from 15.0 to 50.2 µM.

Systematic Nursing Interventions Combined with Continuity of Care in Patients with a Spinal Fracture Complicated with a Spinal Cord Injury and Its Effect on Recovery and Satisfaction.

Objective: The aim of this study is to examine the application value of systematic nursing interventions combined with continuity of care in cases with a spinal fracture complicated with a spinal cord injury and its effect on recovery and satisfaction. Methods: We identified ninety cases with a spinal fracture complicated with a spinal cord injury who were admitted to local hospital from May 2019 to May 2021 as research subjects and assigned them into an experimental group (systematic nursing combined with continuity of care, n = 45) and a control group (conventional nursing, n = 45) according to their admission order. The level of life of all groups between intervention was evaluated with reference to the Generic Quality of Life Inventory-74 (GQOLI-74) Rating Scale. The Hospital Anxiety and Depression (HAD) scale was used to assess the emotional status of patients before and after intervention. The complication rates, nursing outcomes, nursing satisfaction, and rehabilitation outcomes of all cases were calculated. Results: The GQOLI-74 score of the experimental group was higher than that of another group (P < 0.05). Lower HAD scores of experimental group were observed than that of another group (P < 0.05). The experimental group obtained remarkably higher nursing effective rates and higher nursing satisfaction than another group (P < 0.05). Rehabilitation outcome of the experimental group outperformed that another group (P < 0.05). Conclusion: The use of systematic nursing intervention combined with continuity of care for cases with spinal fracture complicated with a spinal cord injury can enhance the nursing effect, effectively relieve cases' psychological pressure, improve patients' level of life and nursing satisfaction, and contribute to the maintenance of a good nurse-patient relationship, which merits clinical promotion.

Systematic identification of molecular mechanisms for aryl hydrocarbon receptor mediated neuroblastoma cell migration.

Tumor cell migration is affected by the aryl hydrocarbon receptor (AhR). However, the systematic molecular mechanisms underlying AhR-mediated migration of human neuroblastoma cells are not fully understood. To address this issue, we performed an integrative analysis of mRNA and microRNA (miR) expression profiles in human neuroblastoma SK-N-SH cells treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a potent agonist of AhR. The cell migration was increased in a time- and concentration- dependent manner, and was blocked by AhR antagonist (CH223191). A total of 4,377 genes were differentially expressed after 24-hour-treatment with 10-10 M TCDD, of which the upregulated genes were significantly enriched in cell migration-related biological pathways. Thirty-four upregulated genes, of which 25 were targeted by 78 differentially expressed miRs, in the axon guidance pathway were experimentally confirmed, and the putative dioxin-responsive elements were present in the promoter regions of most genes (79 %) and miRs (82 %) in this pathway. Furthermore, two promigratory genes (CFL2 and NRP1) induced by TCDD was reversed by blockade of AhR. In conclusion, AhR-mediated mRNA-miR networks in the axon guidance pathway may represent a potential molecular mechanism of dioxin-induced directional migration of human neuroblastoma cells.

The Value of Comprehensive Nursing Intervention on Anxiety in Patients with Acute Heart Failure and Diabetes via Expression of Stress-related Genes.

Many patients with acute heart failure and diabetes experience varying degrees of anxiety upon entering the cardiac intensive care unit, which has adverse effects on the recovery process of these patients. Anxiety syndrome in these patients increases the risk of death up to three times. This study aimed to determine the effect of comprehensive nursing intervention on anxiety in patients with acute heart failure and diabetes by evaluating the expression of stress-related genes, i.e. COMT and BDNF genes. In this clinical trial study, 74 patients with acute heart failure and diabetes hospitalized in the cardiac intensive care unit were selected by convenience sampling method and randomly assigned to intervention and control groups. The control group received routine ward care, and the intervention group received nursing support program-based interventions in three informational, emotional, and physical dimensions in addition to regular care. Beck Anxiety Inventory was completed before and after the intervention in both groups. The expression of COMT and BDNF genes was evaluated by the qRT-PCR technique. Data were analyzed by Mann-Whitney U and independent T-test in SPSS software version 16. Before the intervention, no significant difference was observed between patients' anxiety scores in the intervention and control groups (p = 0.162). While, after the intervention, the anxiety score of the intervention group was lower than the control group (p = 0.02). The expression of COMT gene results showed that this gene expression was no statistical difference between the control group and intervention group, before intervention (p = 0.83). But, after the intervention, the expression of this gene was statistically decreased in the intervention group in comparison with the control group (p = 0.006). The BDNF gene expression results demonstrated that there was no difference between the two groups, before intervention (p = 0.46). After intervention, statistical increase was observed in control group (p = 0.042) and intervention group (p = 0.007). According to the results of this study, the comprehensive nursing intervention reduced patients' anxiety in the intervention group compared to the control group. This result was also confirmed by evaluating the expression of stress-related genes. Therefore, it is suggested that this intervention method be used to reduce anxiety in these patients.

Capsaicin, a Phytochemical From Chili Pepper, Alleviates the Ultraviolet Irradiation-Induced Decline of Collagen in Dermal Fibroblast via Blocking the Generation of Reactive Oxygen Species.

Capsaicin, a major ingredient in chili pepper, has broad pharmaceutical applications, including relieving pain, anti-inflammation, and treating psoriasis. In dermatological biology, capsaicin has been shown to prevent the ultraviolet (UV)-induced melanogenesis via TRPV1 receptor. To strengthen the roles of capsaicin in skin function, the damaged skin, triggered by exposure to UV, was reversed by capsaicin in both in vitro and in vivo models. In cultured dermal fibroblasts, the exposure to UV induced a decrease of collagen synthesis and increases expression of matrix metalloproteinases (MMPs), generation of reactive oxygen species (ROS), and phosphorylation of Erk and c-Jun, and these events subsequently led to skin damage. However, the UV-mediated damages could be reversed by pre-treatment with capsaicin in a dose-dependent manner. The effect of capsaicin in blocking the UV-mediated collagen synthesis was mediated by reducing generation of ROS in dermal fibroblasts, instead of the receptor for capsaicin. Hence, capsaicin has high potential value in applying as an agent for anti-skin aging in dermatology.

Regulation of acetylcholinesterase during the lipopolysaccharide-induced inflammatory responses in microglial cells.

The non-classical function of acetylcholine (ACh) has been reported in neuroinflammation that represents the modulating factor in immune responses via activation of α7 nicotinic acetylcholine receptor (α7 nAChR), i.e., a cholinergic anti-inflammatory pathway (CAP). Acetylcholinesterase (AChE), an enzyme for ACh hydrolysis, has been proposed to have a non-classical function in immune cells. However, the involvement of AChE in neuroinflammation is unclear. Here, cultured BV2 cell, a microglial cell line, and primary microglia from rats were treated with lipopolysaccharide (LPS) to induce inflammation and to explore the regulation of AChE during this process. The expression profiles of AChE, α7 nAChR, and choline acetyltransferase (ChAT) were revealed in BV2 cells. The expression of AChE (G4 form) was induced significantly in LPS-treated BV2 cells: the induction was triggered by NF-κB and cAMP signaling. Moreover, ACh or α7 nAChR agonist suppressed the LPS-induced production of pro-inflammatory cytokines, as well as the phagocytosis of microglia, by activating α7 nAChR and followed by the regulation of NF-κB and CREB signaling. The ACh-induced suppression of inflammation was abolished in AChE overexpressed cells, but did not show a significant change in AChE mutant (enzymatic activity knockout) transfected cells. These results indicate that the neuroinflammation-regulated function of AChE may be mediated by controlling the ACh level in the brain system.

Identification and Mapping of QTL for Stripe Rust Resistance in the Chinese Wheat Cultivar Shumai126.

Stripe rust, caused by Puccinia striiformis f. sp. tritici, is a damaging disease of wheat globally, and breeding resistant cultivars is the best control strategy. The Chinese winter wheat cultivar Shumai126 (SM126) exhibited strong resistance to P. striiformis f. sp. tritici in the field for more than 10 years. The objective of this study was to identify and map quantitative trait loci (QTL) for resistance to stripe rust in a population of 154 recombinant inbred lines (RILs) derived from a cross between cultivars Taichang29 (TC29) and SM126. The RILs were tested in six field environments with a mixture of the Chinese prevalent races (CYR32, CYR33, CYR34, Zhong4, and HY46) of P. striiformis f. sp. tritici and in growth chamber with race CYR34 and genotyped using the Wheat55K single nucleotide polymorphism (SNP) array. Six QTL were mapped on chromosomes 1BL, 2AS, 2AL, 6AS, 6BS, and 7BL, respectively. All QTL were contributed by SM126 except QYr.sicau-2AL. The QYr.sicau-1BL and QYr.sicau-2AS had major effects, explaining 27.00 to 39.91% and 11.89 to 17.11% of phenotypic variances, which may correspond to known resistance genes Yr29 and Yr69, respectively. The QYr.sicau-2AL, QYr.sicau-6AS, and QYr.sicau-6BS with minor effects are likely novel. QYr.sicau-7BL was only detected based on growth chamber seedling data. Additive effects were detected for the combination of QYr.sicau-1BL, QYr.sicau-2AS, and QYr.sicau-2AL. SNP markers linked to QYr.sicau-1BL (AX-111056129 and AX-108839316) and QYr.sicau-2AS (AX-111557864 and AX-110433540) were converted to breeder-friendly Kompetitive allele-specific PCR (KASP) markers that would facilitate the deployment of stripe rust resistance genes in wheat breeding.

Tacrine Induces Endoplasmic Reticulum-Stressed Apoptosis via Disrupting the Proper Assembly of Oligomeric Acetylcholinesterase in Cultured Neuronal Cells.

Acetylcholinesterase inhibitors (AChEIs), the most developed treatment strategies for Alzheimer's disease (AD), will be used in clinic for, at least, the next decades. Their side effects are in highly variable from drug to drug with mechanisms remaining to be fully established. The withdrawal of tacrine (Cognex) in the market makes it as an interesting case study. Here, we found tacrine could disrupt the proper trafficking of proline-rich membrane anchor-linked tetrameric acetylcholinesterase (AChE) in the endoplasmic reticulum (ER). The exposure of tacrine in cells expressing AChE, e.g., neurons, caused an accumulation of the misfolded AChE in the ER. This misfolded enzyme was not able to transport to the Golgi/plasma membrane, which subsequently induced ER stress and its downstream signaling cascade of unfolded protein response. Once the stress was overwhelming, the cooperation of ER with mitochondria increased the loss of mitochondrial membrane potential. Eventually, the tacrine-exposed cells lost homeostasis and underwent apoptosis. The ER stress and apoptosis, induced by tacrine, were proportional to the amount of AChE. Other AChEIs (rivastigmine, bis(3)-cognitin, daurisoline, and dauricine) could cause the same problem as tacrine by inducing ER stress in neuronal cells. The results provide guidance for the drug design and discovery of AChEIs for AD treatment. SIGNIFICANCE STATEMENT: Acetylcholinesterase inhibitors (AChEIs) are the most developed treatment strategies for Alzheimer's disease (AD) and will be used in clinic for at least the next decades. This study reports that tacrine and other AChEIs disrupt the proper trafficking of acetylcholinesterase in the endoplasmic reticulum. Eventually, the apoptosis of neurons and other cells are induced. The results provide guidance for drug design and discovery of AChEIs for AD treatment.

The self-psychological safety maintenance and its influencing factors of community frontline staff during COVID-19 pandemic.

ABSTRACT: The present study was designed to determine the self-psychological safety maintenance and its influencing factors of community staff on the front-line during Coronavirus Disease 2019 (COVID-19) pandemic.A total of 126 frontline staff in community were involved in the current cross-section study. Online questionnaires including the anxiety sensitivity index-3 (ASI-3), patient health questionnaire (PHQ-9), simple coping style questionnaire (SCSQ) and general self-efficacy scale (GSES) were utilized to analyze psychological state, coping style and self-efficacy of the surveyed staff.The ASI-3 standard score of 126 community frontline staff was 10.01 ±â€Š2.82, of which 21 community frontline staff scored > 16, and the detection rate of anxiety was 16.67%. The anxiety state of doctors and nursing staff was significantly lower than that of administrative staff, logistics staff and other staff, and the rate of anxiety of having colleagues with suspected symptoms was significantly higher than that without colleagues with suspected symptoms (P < .05). The PHQ-9 standard score was 2.03 ±â€Š0.16, of which 19 frontline staff in the community scored more than 5, and the detection rate of depression was 15.08%. Among them, the depression state of those with bachelor degree or above was significantly lower than that of those with junior college education, and the rate of depressive symptoms of community frontline staff with colleagues harboring suspected symptoms were significantly higher than those without colleagues with suspected symptoms (P < .05). The aggregated results showed that most of the community frontline staff in anxiety state group and depression group adopted negative coping style while most of the community frontline staff in the non-anxiety group and the non-depression group adopted positive coping style (P < .05). Additionally, lower score of self-efficacy of the community frontline staff was observed in the anxiety state group and the depression state group (P < .05).During the outbreak of COVID-19, several community frontline staff showed negative psychology of anxiety and depression, which could affect their coping style and self-efficacy. Early and effective psychological safety maintenance was required to alleviate the negative psychology of community frontline staff.

Characterization of a macrophagic-like cell line derived from rabbit fish (Siganus fuscescens): An illustration of anti-inflammatory responses of the herbal extract of Scutellaria baicalensis.

A new cell line was isolated and characterized from the head kidney of Siganus fuscescens (rabbit fish). The new macrophagic-like cell line was named as rabbit fish macrophage (RFM), and which could be sub-cultured for over 50 cycles since the development. RFM cell line was tested for growth in different temperatures and serum concentrations: the best growing condition was optimized at 20% serum under 28 °C. In cultured RFM cells, sequencing of 18S rRNA, as well as immunostaining of cytokeratin and CD 68, confirmed the identity as macrophagic cell of S. fuscescens. Cultured RFM cells were exposed to challenge of inflammation, as triggered by LPS, showing highly sensitive responses to inflammation, including release of nitric oxide, expression of cytokine, and activation of phagocytosis. The water extract of aerial part of Scutellaria baicalensis, named as SBA, has been shown anti-inflammatory property in S. fuscescens fish. In order to extend the application of SBA in aquaculture, the extract and its effective flavonoids, i.e. baicalin and scutellarin, were applied in LPS-treated RFM cells. Application of SBA extract, baicalin or scutellarin, inhibited the expressions of LPS-induced inflammatory cytokines, i.e. IL-1ß, TNF-α, as well as the signaling of transcription factor NF-κB. The results support the established RFM cell line could be an ideal in vitro model in drug screening relating to inflammation. Additionally, the notion of SBA herbal extract in fish aquaculture is supported by its efficacy against inflammation.

New perspective on the regulation of acetylcholinesterase via the aryl hydrocarbon receptor.

Acetylcholinesterase (AChE, EC 3.1.1.7) plays important roles in cholinergic neurotransmission and has been widely recognized as a biomarker for monitoring pollution by organophosphate (OP) and carbamate pesticides. Dioxin is an emerging environmental AChE disruptor and is a typical persistent organic pollutant with multiple toxic effects on the nervous system. Growing evidence has shown that there is a significant link between dioxin exposure and neurodegenerative diseases and neurodevelopmental disorders, most of which involve AChE and cholinergic dysfunctions. Therefore, an in-depth understanding of the effects of dioxin on AChE and the related mechanisms of action might help to shed light on the molecular bases of dioxin impacts on the nervous system. In the past decade, the effects of dioxins on AChE have been revealed in cultured cells of different origins and in rodent animal models. Unlike OP and carbamate pesticides, dioxin-induced AChE disturbance is not due to direct inhibition of enzymatic activity; instead, dioxin causes alterations of AChE expression in certain models. As a widely accepted mechanism for most dioxin effects, the aryl hydrocarbon receptor (AhR)-dependent pathway has become a research focus in studies on the mechanism of action of dioxin-induced AChE dysregulation. In this mini-review, the effects of dioxin on AChE and the diverse roles of the AhR pathway in AChE regulation are summarized. Additionally, the involvement of AhR in AChE regulation during different neurodevelopmental processes is discussed. These AhR-related findings might also provide new insight into AChE regulation triggered by diverse xenobiotics capable of interacting with AhR.

Capsaicin Inhibits the Expression of Melanogenic Proteins in Melanocyte via Activation of TRPV1 Channel: Identifying an Inhibitor of Skin Melanogenesis.

Chili pepper belongs to the genus Capsicum of Solanaceae family. Capsaicin is the primary capsaicinoid in placenta and flesh of chili pepper fruit, which has been shown to have various pharmacological functions, including gastric protection, anti-inflammation, and obesity treatment. Here, we revealed that capsaicin as well as chilli extract was able to inhibit synthesis of melanin in melanocytes. In cultured melanocytes, the melanin content was reduced to 54 ± 6.55% and 42 ± 7.41% with p < 0.001 under treatment of 50 µM capsaicin for 24 and 72 h, respectively. In parallel, the protein levels of tyrosinase and tyrosinase-related protein-1 were reduced to 62 ± 8.35% and 48 ± 8.92% with p < 0.001. Such an inhibitory effect of capsaicin was mediated by activation of transient receptor potential vanilloid 1-induced phosphorylation of extracellular signal-regulated kinase. This resulted in a degradation of microphthalmia-associated transcription factor, leading to reduction of melanogenic enzymes and melanin. These results revealed that capsaicin could be an effective inhibitor for skin melanogenesis. Hence, chili pepper, as our daily food, has potential in dermatological application, and capsaicin should be considered as a safe agent in treating hyperpigmentation problems.

Dehydrocorydaline Accounts the Majority of Anti-Inflammatory Property of Corydalis Rhizoma in Cultured Macrophage.

Corydalis Rhizoma (CR) is a commonly used traditional Chinese medicine for its potency in activating blood circulation and analgesia. In clinic, CR extracts or components are commonly used in the treatment of myocardial ischemia, rheumatism, and dysmenorrhea with different types of inflammation. However, due to different mechanism of pain and inflammation, the anti-inflammatory property of CR has not been fully revealed. Here, the major chromatographic peaks of CR extracts in different extracting solvents were identified, and the anti-inflammatory activities of CR extracts and its major alkaloids were evaluated in LPS-treated macrophages by determining expressions of proinflammatory cytokines, IκBα and NF-κB. The most abundant alkaloid in CR extract was dehydrocorydaline, having >50% of total alkaloids. Besides, the anti-inflammatory activities of dehydrocorydaline and its related analogues were demonstrated. The anti-inflammatory roles were revealed in LPS-treated cultured macrophages, including (i) inhibiting proinflammatory cytokines release, for example, TNF-α, IL-6; (ii) suppressing mRNA expressions of proinflammatory cytokines; (iii) promoting IκBα expression and suppressing activation of NF-κB transcriptional element; and (iv) reducing the nuclear translocation of NF-κB. The results supported that dehydrocorydaline was the major alkaloid in CR extract, which, together with its analogous, accounted the anti-inflammatory property of CR.

Interacting with α 7 nAChR is a new mechanism for AChE to enhance the inflammatory response in macrophages.

Acetylcholine (ACh) regulates inflammation via α7 nicotinic acetylcholine receptor (α7 nAChR). Acetylcholinesterase (AChE), an enzyme hydrolyzing ACh, is expressed in immune cells suggesting non-classical function in inflammatory responses. Here, the expression of PRiMA-linked G4 AChE was identified on the surface of macrophages. In lipopolysaccharide-induced inflammatory processes, AChE was upregulated by the binding of NF-κB onto the ACHE promotor. Conversely, the overexpression of G4 AChE inhibited ACh-suppressed cytokine release and cell migration, which was in contrast to that of applied AChE inhibitors. AChEmt, a DNA construct without enzymatic activity, was adopted to identify the protein role of AChE in immune system. Overexpression of G4 AChEmt induced cell migration and inhibited ACh-suppressed cell migration. The co-localization of α7 nAChR and AChE was found in macrophages, suggesting the potential interaction of α7 nAChR and AChE. Besides, immunoprecipitation showed a close association of α7 nAChR and AChE protein in cell membrane. Hence, the novel function of AChE in macrophage by interacting with α7 nAChR was determined. Together with hydrolysis of ACh, AChE plays a direct role in the regulation of inflammatory response. As such, AChE could serve as a novel target to treat age-related diseases by anti-inflammatory responses.

General requirements for stem cells.

The standard 'General requirements for stem cells' is the first set of general guidelines for stem cell research and production in China, jointly drafted and agreed upon by experts from the Chinese Society for Stem Cell Research. This standard specifies the classification, ethical requirements, quality requirements, quality control requirements, detection control requirements and waste disposal requirements of stem cells, which is applicable to stem cell research and production. It was firstly released by the Chinese Society for Cell Biology on 1 August 2017 and was further revised on 30 April 2020. We hope that publication of these guidelines will promote institutional establishment, acceptance, and execution of proper protocols, and accelerate the international standardization of stem cells for clinical development and therapeutic applications.