Eugenol Possesses Colitis Protective Effects: Impacts on the TLR4/MyD88/NF-[Formula: see text]B Pathway, Intestinal Epithelial Barrier, and Macrophage Polarization.

Eugenol (EU) has been shown to ameliorate experimental colitis due to its anti-oxidant and anti-inflammatory bioactivities. In this study, DSS-induced acute colitis was established and applied to clarify the regulation efficacy of EU on intestinal barrier impairment and macrophage polarization imbalance along with the inflammatory response. Besides, the adjusting effect of EU on macrophages was further investigated in vitro. The results confirmed that EU intervention alleviated DSS-induced colitis through methods such as restraining weight loss and colonic shortening and decreasing DAI scores. Microscopic observation manifested that EU maintained the intestinal barrier integrity in line with the mucus barrier and tight junction protection. Furthermore, EU intervention significantly suppressed the activation of TLR4/MyD88/NF-[Formula: see text]B signaling pathways and pro-inflammatory cytokines gene expressions, while enhancing the expressions of anti-inflammatory cytokines. Simultaneously, WB and FCM analyses of the CD86 and CD206 showed that EU could regulate the DSS-induced macrophage polarization imbalance. Overall, our data further elucidated the mechanism of EU's defensive effect on experimental colitis, which is relevant to the protective efficacy of intestinal barriers, inhibition of oxidative stress and excessive inflammatory response, and reprogramming of macrophage polarization. Hence, this study may facilitate a better understanding of the protective action of the EU against UC.

Effects of a mindfulness-based interventions on stress, burnout in nurses: a systematic review and meta-analysis.

Background: Stress in the healthcare environment causes negative effects in nurses such as burnout, anxiety, and depression. The COVID-19 pandemic has resulted in increased pressure on medical staff globally, highlighting the potential benefits of mindfulness-based interventions in reducing nurses' stress levels. Despite numerous studies exploring the effect of mindfulness-based training on nurses, the results remain inconclusive. Objective: To systematically evaluate the impact of mindfulness training on nurse's performance and increase the certainty of existing evidence. Methods: This study searched various databases, including EBSCO, Embase, Web of Science, PubMed, ProQuest, Scopus, Cochrane Online Library, Wanfang, SinoMed, CNKI, and VIP, for randomized controlled trials on the impact of mindfulness-based interventions for nurses up until 02 December 2022. Two investigators independently screened and extracted data from the articles, while also assessing the risk of bias. The data was analyzed using RevMan 5.4 software. Results: This review identified 15 studies out of the 2,171 records retrieved, consisting of a total of 1,165 participants who were randomized. Post-intervention analysis provided very-low certainty evidence of moderate effectiveness of mindfulness-based training in reducing stress [standardized mean difference (SMD) = -0.81; 95% confidence interval (CI) = -1.11 to -0.52], with no significant effect on anxiety (SMD = -0.30; 95% CI = -0.72 to 0.13) or depression (SMD = -0.24; 95% CI = -0.55 to 0.07). However, the training was effective in reducing burnout, as demonstrated by the lower scores for emotional exhaustion (SMD = -4.27; 95% CI = -5.94 to -2.59) and depersonalization (SMD = -2.89; 95% CI = -4.24 to -1.54) and higher scores for personal accomplishment (SMD = 2.81; 95% CI = 0.12 to 5.50). There was a sustained improvement in stress levels in the short-term (≤3 months), with delayed benefits for burnout. However, only two studies were available for later follow-ups, and there was no significant evidence of long-term effects. Conclusion: Mindfulness-based training may be a viable intervention for improving the psychological wellbeing of nurses, including reducing stress, burnout. Systematic review registration: https://www.crd.york.ac.uk/PROSPERO/, identifier CRD42023387081.

A ferroptosis-targeting ceria anchored halloysite as orally drug delivery system for radiation colitis therapy.

Radiation colitis is the leading cause of diarrhea and hematochezia in pelvic radiotherapy patients. This work advances the pathogenesis of radiation colitis from the perspective of ferroptosis. An oral Pickering emulsion is stabilized with halloysite clay nanotubes to alleviate radiation colitis by inhibiting ferroptosis. Ceria nanozyme grown in situ on nanotubes can scavenge reactive oxygen species, and deferiprone was loaded into the lumen of nanotubes to relieve iron stress. These two strategies effectively inhibit lipid peroxidation and rescue ferroptosis in the intestinal microenvironment. The clay nanotubes play a critical role as either a medicine to alleviate colitis, a nanocarrier that targets the inflamed colon by electrostatic adsorption, or an interfacial stabilizer for emulsions. This ferroptosis-based strategy was effective in vitro and in vivo, providing a prospective candidate for radiotherapy protection via rational regulation of specific oxidative stress.

Systematic Analysis of Galactinol Synthase and Raffinose Synthase Gene Families in Potato and Their Expression Patterns in Development and Abiotic Stress Responses.

Raffinose family oligosaccharides (RFOs) are very important for plant growth, development, and abiotic stress tolerance. Galactinol synthase (GolS) and raffinose synthase (RFS) are critical enzymes involved in RFO biosynthesis. However, the whole-genome identification and stress responses of their coding genes in potato remain unexplored. In this study, four StGolS and nine StRFS genes were identified and classified into three and five subgroups, respectively. Remarkably, a total of two StGolS and four StRFS genes in potato were identified to form collinear pairs with those in both Arabidopsis and tomato, respectively. Subsequent analysis revealed that StGolS4 exhibited significantly high expression levels in transport-related tissues, PEG-6000, and ABA treatments, with remarkable upregulation under salt stress. Additionally, StRFS5 showed similar responses to StGolS4, but StRFS4 and StRFS8 gene expression increased significantly under salt treatment and decreased in PEG-6000 and ABA treatments. Overall, these results lay a foundation for further research on the functional characteristics and molecular mechanisms of these two gene families in response to ABA, salt, and drought stresses, and provide a theoretical foundation and new gene resources for the abiotic-stress-tolerant breeding of potato.

Exploring the potential of mindfulness-based therapy in the prevention and treatment of neurodegenerative diseases based on molecular mechanism studies.

Neurodegenerative diseases (ND) have received increasing attention due to their irreversibility, but there is still no means to completely cure ND in clinical practice. Mindfulness therapy (MT), including Qigong, Tai Chi, meditation, and yoga, etc., has become an effective complementary treatment modality in solving clinical and subclinical problems due to its advantages of low side effects, less pain, and easy acceptance by patients. MT is primarily used to treat mental and emotional disorders. In recent years, evidence has shown that MT has a certain therapeutic effect on ND with a potential molecular basis. In this review, we summarize the pathogenesis and risk factors of Alzheimer's disease (AD), Parkinson's disease (PD), and amyotrophic lateral sclerosis (ALS), relating to telomerase activity, epigenetics, stress, and the pro-inflammatory transcription factor nuclear factor kappa B (NF-κB) mediated inflammatory response, and analyze the molecular mechanism basis of MT to prevent and treat ND, to provide possible explanations for the potential of MT treatments for ND.

Capilliposide B inhibits the migration of prostate cancer by inducing autophagy through the ROS/AMPK/mTOR pathway.

Capilliposide B (CPS-B), a novel oleanane triterpenoid saponin derived from Lysimachia capillipes Hemsl, is a potent anticancer agent. However, its anticancer mechanism remains elusive. In the present study, we demonstrated the potent anti-tumor activity and molecular mechanism of CPS-B both in vitro and in vivo. Proteomic analysis using isobaric tags for relative and absolute quantitation techniques suggested that CPS-B modulated autophagy in prostate cancer (PC). Moreover, Western blotting showed that both autophagy and epithelial-mesenchymal transition occurred place after CPS-B treatment in vivo, which was also proven in PC-3 cancer cells. We deduced that CPS-B inhibited migration by inducing autophagy. We examined the accumulation of reactive oxygen species (ROS) in cells, and in downstream pathways, LKB1 and AMPK were activated while mTOR was inhibited. Transwell experiment results showed that CPS-B inhibited the metastasis of PC-3 cells and that this effect was significantly attenuated after pretreatment with chloroquine, indicating that CPS-B inhibited metastasis via autophagy induction. Altogether, these data suggest that CPS-B is a potential therapeutic agent for cancer treatment that acts by inhibiting migration through the ROS/AMPK/mTOR signaling pathway.

Effectiveness and safety of acupuncture for post-stroke spasticity: A systematic review and meta-analysis.

Objective: This systematic review and meta-analysis aimed to comprehensively evaluate the effectiveness and safety of acupuncture for post-stroke spasticity. Methods: Nine electronic databases were searched from their inception to 6 June 2022, to identify randomized-controlled trials (RCTs) that investigated the effectiveness and safety of acupuncture for post-stroke spasticity. Two reviewers independently screened the studies, extracted the data, assessed the risk of bias. The reporting quality of interventions in controlled trials of acupuncture was evaluated using Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). The RevMan 5.4 and R 4.2.0 software were used for statistical analysis. Results: A total of 88 eligible studies were included, involving 6,431 individuals. The pooled data demonstrated that acupuncture combined with conventional rehabilitation (CR) was superior to CR in reducing the Modified Ashworth Scale (MAS) score (standardized mean difference [SMD] = -0.73; 95% CI = -0.83 to -0.63; I 2 = 65%; low certainty of evidence). The favorable results were also observed in comparisons of acupuncture vs. CR (SMD = -0.22, 95% CI = -0.36 to -0.07; I 2 = 49%; moderate certainty of evidence). Subgroup analysis showed that acupuncture treatment with a frequency of once or twice a day was more effective than CR. In addition, the antispasmodic effect of acupuncture treatment increased with more sessions. Four studies explicitly reported slight acupuncture-related adverse events. Conclusion: Acupuncture could be recommended as adjuvant therapy for spasticity after stroke. However, due to the high risk of bias and heterogeneity of the included studies, the effectiveness of acupuncture for post-stroke spasticity remains to be confirmed.

Determination of components in Radix paeoniae rubra based on QAMS.

The current study aimed to establish simple and quick quality evaluation method of Chishao based on QAMS. Oxypaeoniflorin is used as a marker in the Chishao root. Based on it, the content of other components could be obtained by establishing the mathematical relationship. UPLC method was used to collect data, and the detection wavelengths were 230nm (benzoic acid, paeoniflorin), 263nm (hydroxy paeoniflorin) 274nm (gallic acid, paeoniflorin, catechin), respectively. The stationary phase was an Agilent ZORBAX SB-C18 and the mobile phase was acetonitrile -0.1% formic acid-water. The gradient elution method was adopted at the certain flow rate (0.3 mL/min). The column temperature set 40oC, and the injection volume was 1µL. Multiple reaction monitoring mode was selected for data collection. The linear ranges of benzoic acid, paeoniflorin, hydroxy-paeoniflorin, gallic acid, catechin and paeoniflorinhad good linearity (r ≥0.9995). The UPLC method was established to determine the content of paeoniflorin, benzoic acid, catechin, gallic acid, paeoniflorin, andhydroxy-paeoniflorin in Radix Paeoniae Rubra. In the current study, the method for the chemical components in Radix Paeoniae Rubra to provide the evaluation basis of medicinal effects.

[Identification of Bacterial Flora and Metabolic Function of Sediments in Different Channels of Duliujian River Basin, Tianjin].

Bacterial communities are highly sensitive to environmental changes, but their metabolic functions may be convergent under similar ecological conditions. In order to test this environmental attribute of the bacterial community and verify the feasibility in using the bacterial metabolic data to divide functional units at the river basin scale, the surface sediments in three continuous spatial units of the main stream (MS), left tributary (LT), and right tributary (RT) of the Duliujian River basin were selected as the research objects. Therefore, 16S rDNA high-throughput sequencing and the PICRUSt platform were used to analyze the bacterial diversity and metabolic function of sediments in different units. The results showed that there were no significant differences for the Shannon and Simpson indices between the different river channels (P>0.05); however, the bacterial diversity indices of Chao1, ACE, Observed_species, and PD_whole_tree of LT and RT were significantly higher than those of the MS (P<0.05). Moreover, the dominant bacterial phyla were not significantly different among the different river channels. In the present study, a total of 41 metabolic pathways were predicted based on the KEGG database, among which 34 metabolic pathways such as membrane transport, amino acid metabolism, and carbohydrate metabolism were significantly different. The functional metabolic abundance was higher in MS than that in RT and LT (P<0.05); however, there was no significant difference between those of RT and LT (P>0.05). Except for exchangeable phosphorus and nitrate nitrogen, there were no significant differences in other physicochemical properties among the different river channels (P>0.05). Furthermore, pH and iron/aluminum-phosphorus were found to significantly affect the bacterial structure, and SOM and TN were found to significantly affect the bacterial metabolic function. Overall, the sediments of MS and tributaries (LT and RT) of the river were clearly divided into level-1 and level-2 groups, indicating that the metabolic abundance of the bacterial community can be used as the key indicator in the division of functional units at the river basin scale. This study provided a theoretical basis and technical support for ecological functional division and management in coastal river basins.

Melatonin Prevents NaAsO2-Induced Developmental Cardiotoxicity in Zebrafish through Regulating Oxidative Stress and Apoptosis.

Melatonin is an indoleamine hormone secreted by the pineal gland. It has antioxidation and anti-apoptosis effects and a clear protective effect against cardiovascular diseases. Our previous studies demonstrated that embryonic exposure to sodium arsenite (NaAsO2) can lead to an abnormal cardiac development. The aim of this study was to determine whether melatonin could protect against NaAsO2-induced generation of reactive oxygen species (ROS), oxidative stress, apoptosis, and abnormal cardiac development in a zebrafish (Danio rerio) model. We found that melatonin decreased NaAsO2-induced zebrafish embryonic heart malformations and abnormal heart rates at a melatonin concentration as low as 10-9 mol/L. The NaAsO2-induced oxidative stress was counteracted by melatonin supplementation. Melatonin blunted the NaAsO2-induced overproduction of ROS, the upregulation of oxidative stress-related genes (sod2, cat, gpx, nrf2, ho-1), and the production of antioxidant enzymes (Total SOD, SOD1, SOD2, CAT). Melatonin attenuated the NaAsO2-induced oxidative damage, DNA damage, and apoptosis, based on malonaldehyde and 8-OHdG levels and apoptosis-related gene expression (caspase-3, bax, bcl-2), respectively. Melatonin also maintained the control levels of heart development-related genes (nkx2.5, sox9b) affected by NaAsO2. In conclusion, melatonin protected against NaAsO2-induced heart malformations by inhibiting the oxidative stress and apoptosis in zebrafish.

Betaine Alleviates High-Fat Diet-Induced Disruptionof Hepatic Lipid and Iron Homeostasis in Mice.

Non-alcoholic fatty liver disease (NAFLD) is characterized by excessive fat deposition in the liver, which is often associated with disrupted iron homeostasis. Betaine has been reported to be hepatoprotective, yet whether and how betaine ameliorates high-fat diet-induced disruption of hepatic lipid and iron homeostasis remains elusive. In this study, mice were fed either standard (CON) or high-fat diet (HFD) for 9 weeks to establish a NAFLD model. Mice raised on HF diet were then assigned randomly to HF and HFB groups, HFB group being supplemented with 1% (w/v) of betaine in the drinking water for 13 weeks. Betaine supplementation significantly alleviated excessive hepatic lipid deposition and restored hepatic iron content. Betaine partly yet significantly reversed HFD-induced dysregulation of lipogenic genes such as PRARγ and CD36, as well as the iron-metabolic genes including FPN and HAMP that encodes hepcidin. Similar mitigation effects of betaine were observed for BMP2 and BMP6, the up-stream regulators of hepcidin expression. Betaine significantly rectified disrupted expression of methyl transfer gene, including BHMT, GNMT and DNMT1. Moreover, HFD-modified CpG methylation on the promoter of PRARγ and HAMP genes was significantly reversed by betaine supplementation. These results indicate that betaine alleviates HFD-induced disruption of hepatic lipid and iron metabolism, which is associated with modification of CpG methylation on promoter of lipogenic and iron-metabolic genes.

Dendrobium nobile protects against ovalbumin-induced allergic rhinitis by regulating intestinal flora and suppressing lung inflammation.

Antibiotic exposure-induced dysbiosis of the intestinal flora increases the risk of developing allergic rhinitis. Hence, regulating the balance of intestinal flora may be useful for preventing and treating allergic rhinitis. However, the underlying mechanism is unclear. Dendrobium nobile (Shihu) exhibits anti-inflammatory and immune activities. Hence, in this study, we investigated the mechanism via which Shihu may improve allergic rhinitis. Mouse models of allergic rhinitis with intestinal flora dysbiosis (Model-D, antibiotics induce intestinal flora dysbiosis with ovalbumin-induced allergy) and normal intestinal flora with allergic rhinitis (Model-N, ovalbumin-induced allergy) were established. The effect of Shihu on intestinal flora and inflammation caused during allergic rhinitis were analyzed. Allergic symptoms, infiltration of hematoxylin and eosin in the lungs and nose, and the release of various factors [interleukin (IL)-2, IL-4, IFN-γ, IL-6, IL-10, and IL-17] in the lungs were evaluated. The results indicate that intestinal flora dysbiosis exacerbated lung and nose inflammation in allergic rhinitis. However, treatment with the Shihu extract effectively reversed these symptoms. Besides, the Shihu extract inhibited the PI3K/AKT/mTOR pathway and increased the level of Forkhead box protein in the lungs. Additionally, the Shihu extract reversed intestinal flora dysbiosis at the phylum and genus levels and improved regulator T cell differentiation. Furthermore, in the Model-D group, the Shihu extract inhibited the decrease in the diversity and abundance of the intestinal flora. Screening was performed to determine which intestinal flora was positively correlated with Treg differentiation using Spearman's correlation analysis. In conclusion, we showed that Shihu extract restored the balance in intestinal flora and ameliorated inflammation in the lungs of allergic rhinitis mice and predicted a therapeutic new approach using Traditional Chinese Medicine to improve allergic rhinitis.

Transcriptome Analysis of Stephania tetrandra and Characterization of Norcoclaurine-6-O-Methyltransferase Involved in Benzylisoquinoline Alkaloid Biosynthesis.

Stephania tetrandra (S. Moore) is a source of traditional Chinese medicine that is widely used to treat rheumatism, rheumatoid arthritis, edema, and hypertension. Benzylisoquinoline alkaloids (BIAs) are the main bioactive compounds. However, the current understanding of the biosynthesis of BIAs in S. tetrandra is poor. Metabolite and transcriptomic analyses of the stem, leaf, xylem, and epidermis of S. tetrandra were performed to identify candidate genes associated with BIAs biosynthesis. According to the metabolite analysis, the majority of the BIAs accumulated in the root, especially in the epidermis. Transcriptome sequencing revealed a total of 113,338 unigenes that were generated by de novo assembly. Among them, 79,638 unigenes were successfully annotated, and 42 candidate structural genes associated with 15 steps of BIA biosynthesis identified. Additionally, a new (S)-norcoclaurine-6-O-methyltransferase (6OMT) gene was identified in S. tetrandra, named St6OMT2. Recombinant St6OMT2 catalyzed (S)-norcoclaurine methylation to form (S)-coclaurine in vitro. Maximum activity of St6OMT2 was determined at 30°C and pH 6.0 in NaAc-HAc buffer. Its half-life at 50°C was 22 min with the Km and kcat of 28.2 µM and 1.5 s-1, respectively. Our results provide crucial transcriptome information for S. tetrandra, shedding light on the understanding of BIAs biosynthesis and further gene functional characterization.

Allometric releases of nitrogen and phosphorus from sediments mediated by bacteria determines water eutrophication in coastal river basins of Bohai Bay.

Although the Chinese government has conducted much work in recent years to reduce land-based pollutant discharge, eutrophication continues to occur frequently in many rivers, estuaries, and coastal waters. This may indicate that sediment is a major source rather than a sink for nitrogen (N) and phosphorus (P). To clarify the endogenous mechanisms of eutrophication in coastal river basins, the eutrophication status, physicochemical properties, and bacterial parameters of overlying waters and sediments in the catchment (CA), estuarine (EA), and offshore (OA) areas in the Duliujian River Basin of Bohai Bay were investigated. The results showed that the eutrophication index (EI) of CA, EA, and OA were 62.71, 57.86, and 36.51, respectively. The EI was more sensitive to increases in P (slope = 3.887) than to increases in N (slope = 0.734) of the overlying water, indicating that P is the main factor driving eutrophication in the coastal river basin. However, a nonlinear relationship was found between P in sediments and overlying waters, suggesting that bacterial mediation may occur during P release. As speculated in this study, P in the overlying water increased more quickly than N with increasing bacterial diversity and metabolic abundance, indicating that the allometric release of N and P mediated by bacteria increases the risk of eutrophication. Redundancy analysis showed that organic matter and total N in sediment have positive effects on bacterial communities, which explains 21.8% and 23.7% variation in bacterial diversity, and explains 31.3% and 7.1% variation in bacterial metabolism. This also suggests that the accumulation of N in the sediment promotes the release of P and further aggravates the eutrophication of water. Therefore, simultaneous control of N and P is necessary to control water eutrophication in coastal river basins.

Acupuncture for tension-type headache: a systematic review and meta-analysis of randomized controlled trials.

Background: Tension-type headache (TTH) is the most common neurologic disease worldwide. Acupuncture is commonly applied to treat TTH, but evidence of acupuncture for TTH is contradictory based on previous meta-analyses. Therefore, we conducted this systematic review and meta-analysis to update the evidence of acupuncture for TTH and aimed to provide a valuable reference for clinical application. Methods: We searched 9 electronic databases from their inceptions to July 1, 2022 for randomized controlled trials (RCTs) of acupuncture for TTH. We also manually searched reference lists and relevant websites, and the experts in this field were consulted for possible eligible studies. Two independent reviewers conducted literature screening, data extraction, and risk of bias assessment. The revised Cochrane risk-of-bias tool (ROB 2) was used to assess the risk of bias of included studies. Subgroup analyses were carried out based on frequency of acupuncture, total sessions, treatment duration, needle retention, types of acupuncture and categories of medication. Data synthesis was performed using Review Manager 5.3 and Stata 16. The Grading of Recommendations Assessment, Development and Evaluation Approach (GRADE) was used to evaluate the certainty of evidence of each outcome. Meanwhile, the Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA) was used to assess the reporting quality of interventions in clinical trials of acupuncture. Results: 30 RCTs involving 2,742 participants were included. According to ROB 2, 4 studies were considered as low risk, and the rest studies were some concerns. After treatment, compared with sham acupuncture, acupuncture had greater effect in improvement of responder rate [3 RCTs, RR = 1.30, 95%CI (1.13, 1.50), I2 = 2%, moderate certainty] and headache frequency [5 RCTs, SMD = -0.85, 95%CI (-1.58, -0.12), I2 = 94%, very low certainty]. In contrast to medication, acupuncture was more effective to reduce pain intensity [9 RCTs, SMD = -0.62, 95%CI (-0.86, -0.38), I2 = 63%, low certainty]. Adverse events were evaluated in 16 trials, and no serious event associated with acupuncture occurred. Conclusions: Acupuncture may be an effective and safe treatment for TTH patients. Due to low or very low certainty of evidence and high heterogeneity, more rigorous RCTs are needed to verify the effect and safety of acupuncture in the management of TTH.

The effects of acupuncture therapy in migraine: An activation likelihood estimation meta-analysis.

Background: Previous functional magnetic resonance imaging studies indicated that acupuncture could activate the brain regions in patients with migraine. However, these studies showed inconsistent results. This activation likelihood estimation (ALE) meta-analysis aimed to investigate the consistent activated change of brain regions between pre- and post-acupuncture treatment in migraineurs. Methods: We conducted a literature search in PubMed, Embase, Web of Science, the Cochrane Library, the China National Knowledge Infrastructure, the Chinese Science and Technology Periodical Database, the Wanfang Database, and the Chinese Biomedical Literature Database from their inception to 18 August, 2022, to obtain articles assessing the functional magnetic resonance imaging changes of acupuncture for migraine. Two investigators independently performed literature selection, data extraction, and quality assessment. The methodological quality was assessed with a modified version of the checklist. The reporting quality of interventions among included studies was evaluated by the Revised Standards for Reporting Interventions in Clinical Trials of Acupuncture (STRICTA). Our meta-analysis was conducted according to the GingerALE software. The Jackknife sensitivity analysis was used to assess the robustness of the results. Results: 14 articles were finally included according to the eligible criteria. Regarding the immediate effect of acupuncture on migraine, the ALE meta-analysis demonstrated that the deactivation regions were mainly located in the superior frontal gyrus, and middle frontal gyrus (uncorrected P < 0.001). The ALE meta-analysis of the cumulative effect showed that the activation regions were the thalamus, superior frontal gyrus, posterior lobe of the cerebellum, insula, middle frontal gyrus, precentral gyrus, anterior cingulate, and the deactivation brain regions were located in the transverse temporal gyrus, postcentral gyrus, superior temporal gyrus, anterior cingulate, parahippocampal gyrus, inferior parietal lobule, and inferior occipital gyrus (uncorrected P < 0.001). Conclusion: Acupuncture could activate multiple brain areas related with the regulation of pain conduction, processing, emotion, cognition, and other brain regions in patients with migraine. In the future, the combination of multiple imaging technologies could be a new approach to deeply investigate the central mechanism of acupuncture for migraine.

Discovery and Nanosized Preparations of (S,R)-Tylophorine Malate as Novel anti-SARS-CoV-2 Agents.

The coronavirus disease 2019 (COVID-19) pandemic caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has stimulated the search for effective drugs for its prevention and treatment. Natural products are an important source for new drug discovery. Here, we report that, NK007(S,R), a tylophorine malate, displays high antiviral activity against SARS-CoV-2 with an EC50 0.03 µM in vitro, which is substantially lower than that of remdesivir (EC50: 0.8 µM in vitro), the only authorized drug to date. The histopathological research revealed that NK007(S,R) (5 mg/kg/dose) displayed a protection effect in lung injury induced by SARS-CoV-2, which is better than remdesivir (25 mg/kg/dose). We also prepared two nanosized preparations of NK007(S,R), which also showed good efficacy (EC50: NP-NK007, 0.007 µM in vitro; LP-NK007, 0.014 µM in vitro). Our findings suggest that tylophora alkaloids, isolated from the traditional Chinese medicine Cynanchum komarovii AL, offer a new skeleton for the development of anticoronavirus drug candidate.

Cell Membrane-Coated Halloysite Nanotubes for Target-Specific Nanocarrier for Cancer Phototherapy.

Naturally-occurring halloysite nanotubes (HNTs) have many advantages for constructing target-specific delivery of phototherapeutic agents. Here, HNTs were labeled with fluorescein isothiocyanate (FITC) and loaded with the type-II photosensitizer indocyanine green (ICG) for phototherapy. HNTs-FITC-ICG was structurally stable due to presence of HNTs as the nanocarrier and protective agent. The nanocarrier was further wrapped with red blood cell membrane (RBCM) to enhance the biocompatibility. The HNTs-FITC-ICG-RBCM nanocarrier show high cytocompatibility and hemocompatibility. Due to the photothermal effect of ICG, a significant temperature rising was achieved by irradiation of the nanocarrier using 808 nm laser. The photothermal temperature rising was used to kill the cancer cells effectively. The HNTs-FITC-ICG-RBCM nanocarrier was further linked with anti-EpCAM to endow it with targeting therapy performance against breast cancer, and the anti-EpCAM-conjugated nanocarrier exhibited significantly tumor-specific accumulation. The RBCM-coated and biocompatible HNTs nanocarrier is a promising candidate for target-specific therapy of cancer.

Phytochemistry, pharmacology, and potential clinical applications of saffron: A review.

ETHNOPHARMACOLOGICAL RELEVANCE: Saffron, the dried red stigma of the perennial herb Crocus sativus L. (Iridaceae), is one of the most important and expensive spices in the world. It is used as a traditional Chinese medicine with demonstrated effects in promoting blood circulation and suppressing blood stasis, cooling blood detoxification, and relieving depression. It is mainly used for the treatment of depression, irregular menstruation, postpartum thrombosis, and bruises. AIM OF THE STUDY: This review aims to provide a systematic and up-to-date overview of the phytochemistry, pharmacology, and clinical applications of saffron. We hope it could provide useful references and guidance for the future directions of research on saffron. MATERIALS AND METHODS: The online database, such as Web of Science, Google Scholar, Science Direct, PubMed, SpringerLink, Wiley Online Library, SciFinder and Chemical book, and CNKI were used to collect relevant literature. And the classic books about Chinese herbal medicine were also being referenced. RESULTS: More than 150 chemical compounds, including carotenoids, flavonoids and flavonoid glycosides, monoterpenes and monoterpenoid derivatives, monocyclic aromatic hydrocarbons, amino acids, alkaloids and others, were revealed. The pharmacological activities study of saffron were focused on the antioxidant, anti-inflammatory, antitumor, antidepressant, hypoglycemic, hypolipidemic, memory-enhancing, and so on. Currently, saffron is mainly used for the treatment of diabetes, Alzheimer's disease, depression, anxiety disorders, cardiovascular diseases, learning and memory disorders, cancer, and other conditions. CONCLUSIONS: Phytochemical and pharmacological analyses of saffron have been revealed in recent studies. However, clinical studies have focused mainly on AD, depression and anxiety disorders. Therefore, a large number of clinical trials are needed to study the efficacy of saffron and its major chemical components against other diseases including hypertension, hyperlipidemia, and cancer. Further studies of the mechanism of action and toxicological properties of saffron are also required, especially research to establish an effective dose of saffron and its long-term toxicity in vivo.