Development of novel hybrid 3D-printed degradable artificial joints incorporating electrospun pharmaceutical- and growth factor-loaded nanofibers for small joint reconstruction.

Small joint reconstruction remains challenging and can lead to prosthesis-related complications, mainly due to the suboptimal performance of the silicone materials used and adverse host reactions. In this study, we developed hybrid artificial joints using three-dimensional printing (3D printing) for polycaprolactone (PCL) and incorporated electrospun nanofibers loaded with drugs and biomolecules for small joint reconstruction. We evaluated the mechanical properties of the degradable joints and the drug discharge patterns of the nanofibers. Empirical data revealed that the 3D-printed PCL joints exhibited good mechanical and fatigue properties. The drug-eluting nanofibers sustainedly released teicoplanin, ceftazidime, and ketorolac in vitro for over 30, 19, and 30 days, respectively. Furthermore, the nanofibers released high levels of bone morphogenetic protein-2 and connective tissue growth factors for over 30 days. An in vivo animal test demonstrated that nanofiber-loaded joints released high concentrations of antibiotics and analgesics in a rabbit model for 28 days. The animals in the drug-loaded degradable joint group showed greater activity counts than those in the surgery-only group. The experimental data suggest that degradable joints with sustained release of drugs and biomolecules may be utilized in small joint arthroplasty.

Disrupted properties of functional brain networks in major depressive disorder during emotional face recognition: an EEG study via graph theory analysis.

Previous neuroimaging studies have revealed abnormal brain networks in patients with major depressive disorder (MDD) in emotional processing. While any cognitive task consists of a series of stages, little is yet known about the topology of functional brain networks in MDD for these stages during emotional face recognition. To address this problem, electroencephalography (EEG)-based functional brain networks of MDD patients at different stages of facial information processing were investigated in this study. First, EEG signals were collected from 16 patients with MDD and 18 age-, gender-, and education-matched normal subjects when performing an emotional face recognition task. Second, the global field power (GFP) method was employed to divide group-averaged event-related potentials into different stages. Third, using the phase transfer entropy (PTE) approach, the brain networks of MDD patients and normal individuals were constructed for each stage in negative and positive face processing, respectively. Finally, we compared the topological properties of brain networks of each stage between the two groups using graph theory approaches. The results showed that the analyzed three stages of emotional face processing corresponded to specific neurophysiological phases, namely, visual perception, face recognition, and emotional decision-making. It was also demonstrated that depressed patients showed abnormally decreased characteristic path length at the visual perception stage of negative face recognition and normalized characteristic path length in the stage of emotional decision-making during positive face processing compared to healthy subjects. Furthermore, while both the MDD and normal groups' brain networks were found to exhibit small-world network characteristics, the brain network of patients with depression tended to be randomized. Moreover, for patients with MDD, the centro-parietal region may lose its status as a hub in the process of facial expression identification. Together, our findings suggested that altered emotional function in MDD patients might be associated with disruptions in the topological organization of functional brain networks during emotional face recognition, which further deepened our understanding of the emotion processing dysfunction underlying MDD.

Water storage capacity is inversely associated with xylem embolism resistance in tropical karst tree species.

Tropical karst habitats are characterized by limited and patchy soil, large rocky outcrops and porous substrates, resulting in high habitat heterogeneity and soil moisture fluctuations. Xylem hydraulic efficiency and safety can determine the drought adaptation and spatial distribution of woody plants growing in karst environments. In this study, we measured sapwood-specific hydraulic conductivity (Ks), vulnerability to embolism, wood density, saturated water content, and vessel and pit anatomical characteristics in the branch stems of 12 evergreen tree species in a tropical karst seasonal rainforest in southwestern China. We aimed to characterize the effects of structural characteristics on hydraulic efficiency and safety. Our results showed that there was no significant correlation between Ks and hydraulic safety across the tropical karst woody species. Ks was correlated with hydraulic vessel diameter (r = 0.80, P < 0.05) and vessel density (r = -0.60, P < 0.05), while the stem water potential at 50 and 88% loss of hydraulic conductivity (P50 and P88) were both significantly correlated with wood density (P < 0.05) and saturated water content (P = 0.052 and P < 0.05, respectively). High stem water storage capacity was associated with low cavitation resistance possibly because of its buffering the moisture fluctuations in karst environments. However, both Ks and P50/P88 were decoupled from the anatomical traits of pit and pit membranes. This may explain the lack of tradeoff between hydraulic safety and efficiency in tropical karst evergreen tree species. Our results suggest that diverse hydraulic trait combination may facilitate species coexistence in karst environments with high spatial heterogeneity.

Allyl isothiocyanate induces DNA damage and inhibits DNA repair-associated proteins in a human gastric cancer cells in vitro.

Allyl isothiocyanate (AITC) is abundant in cruciferous vegetables and it present pharmacological activity including anticancer activity in many types of human cancer cells in vitro and in vivo. Currently, no available information to show AITC affecting DNA damage and repair-associated protein expression in human gastric cancer cells. Therefore, in the present studies, we investigated AITC-induced cytotoxic effects on human gastric cancer in AGS and SNU-1 cells whether or not via the induction of DNA damage and affected DNA damage and repair associated poteins expressions in vitro. Cell viability and morphological changes were assayed by flow cytometer and phase contrast microscopy, respectively, the results indicated AITC induced cell morphological changes and decreased total viable cells in AGS and SNU-1 cells in a dose-dependently. AITC induced DNA condensation and damage in a dose-dependently which based on the cell nuclei was stained by 4', 6-diamidino-2-phenylindole present in AGS and SNU-1 cells. DNA damage and repair associated proteins expression in AGS and SNU-1 cells were measured by Western blotting. The results indicated AITC decreased nuclear factor erythroid 2-related factor 2 (NRF2), heme oxygenase-1 (HO-1), glutathione, and catalase, but increased superoxide dismutase (SOD (Cu/Zn)), and nitric oxide synthase (iNOS) in AGS cells, however, in SNU-1 cells are increased HO-1. AITC increased DNA-dependent protein kinase (DNA-PK), phosphorylation of gamma H2A histone family member X on Ser139 (γH2AXpSer139 ), and heat shock protein 90 (HSP90) in AGS cells. AITC increased DNA-PK, mediator of DNA damage checkpoint protein 1 (MDC1), γH2AXpSer139 , topoisomerase II alpha (TOPIIα), topoisomerase II beta (TOPIIß), HSP90, and heat shock protein 70 (HSP70) in SNU-1 cells. AITC increased p53, p53pSer15 , and p21 but decreased murine double minute 2 (MDM2)pSer166 and O6 -methylguanine-DNA methyltransferase (MGMT) in AGS cells; however, it has a similar effect of AITC except increased ataxia telangiectasia and Rad3 -related protein (ATR)pSer428 , checkpoint kinase 1 (CHK1), and checkpoint kinase 2 (CHK2) in SNU-1 cells. Apparently, both cell responses to AITC are different, nonetheless, all of these observations suggest that AITC inhibits the growth of gastric cancer cells may through induction off DNA damage in vitro.

[Distribution Characteristics, Source Analysis and Potential Ecological Risk Assessment of Soil Heavy Metals in Typical River Source Areas of Northeastern Hunan Province].

Soil environmental quality in water source areas related to the residents' life, health and safety, has been the hotspot issues in science of ecological environment protection. A total of 87 surface soil samples were collected from typical river source areas in northeastern Hunan Province, using GIS technique and potential ecological risk assessment index to study the spatial distribution characteristics and Potential ecological risk of soil heavy metals (Cd, Pb, Cr, Hg and As), and the means of multivariate statistical analysis and positive definite matrix factor analysis models (PMF) were used to explain the possible sources and its contribution rates of heavy metals. The results show that:① The soil located in the typical river source area of northeastern Hunan Province was acidic, and the meant of ω(Cd), ω(Pb), ω(Cr), ω(Hg), and ω(As) in soil was 0.20, 41.07, 130.51, 0.29, and 11.63mg·kg-1, respectively. And except As, all of them had enrichment tendency. ② The comprehensive potential ecological risk of soil heavy metals was at a medium level, among which Cr, Pb and As were at a slight level of potential ecological risk, and Cd and Hg all reached a strong level of risk. ③ Cd and Pb of soil had significant homology, which were derived from agricultural activity, Cr and As of soil were affected by both domestic waste discharge and natural parent material, and Hg of soil was mainly derived from fossil combustion and transportation. ④ There were four pollution sources which included household waste discharge source, natural parent material source, Fossil burning and transportation sources, as well as sources of agricultural activities in typical river source area in northeastern Hunan Province, which contributed the rates of heavy metals were 21.36%, 35.92%, 19.30% and 23.42%, respectively, and the contribution rate of man-made sources was higher than that of natural sources. To sum up, this study has reference value for pollution prevention, ecological restoration and beautiful village construction in river source area of northeastern Hunan Province.

Effect of different chemotherapy schemes on early-stage breast cancer patients with Low HER-2 expression.

Objective: To explore the effect of different chemotherapy schemes on the prognosis, immune function and adverse reactions of breast cancer patients with low HER-2 expression after surgery. Methods: A retrospective analysis was carried out on the clinical data of 60 breast cancer patients with low HER-2 expression in Wuxi No.2 people's Hospital from January 2018 to December 2019. The enrolled patients were divided into two groups according to the different chemotherapy schemes. Patients in the DC group were treated with polyethylene glycol-coated liposome-encapsulated doxorubicin+cyclophosphamide, and those in the TC group were treated with TC (docetaxel+cyclophosphamide). Further comparison was performed on the difference in prognosis, immune function and adverse reaction between the two groups after different chemotherapy schemes. Results: After four courses of treatment, the IgG, CD4+ and CD4+/CD8+ values in the DC group after treatment were higher than those before treatment, while the IgG, CD3+ and CD4+values in the TC group after treatment were lower than those before treatment(P<0.05). Meanwhile, the IgG, CD4+ and CD4+/CD8+ values in the DC group were better than those in the TC group after treatment(P<0.05). During the treatment, the adverse reactions of leukopenia, alopecia, nausea and vomiting in the DC group were significantly lower than those in the TC group(P<0.05). Conclusion: The chemotherapy combination of liposome-encapsulated doxorubicin+cyclophosphamide can significantly improve immune function and greatly reduce the occurrence of adverse reactions in early-stage breast cancer patients with low HER-2 expression after surgery. It has the same effect as docetaxel+cyclophosphamide in improving the prognosis of patients.

Rice Bran Supplementation Ameliorates Gut Dysbiosis and Muscle Atrophy in Ovariectomized Mice Fed with a High-Fat Diet.

Rice bran, a byproduct of rice milling, is rich in fiber and phytochemicals and confers several health benefits. However, its effects on gut microbiota and obesity-related muscle atrophy in postmenopausal status remain unclear. In this study, we investigated the effects of rice bran on gut microbiota, muscle synthesis, and breakdown pathways in estrogen-deficient ovariectomized (OVX) mice receiving a high-fat diet (HFD). ICR female mice were divided into five groups: sham, OVX mice receiving control diet (OC); OVX mice receiving HFD (OH); OVX mice receiving control diet and rice bran (OR); and OVX mice receiving HFD and rice bran (OHR). After twelve weeks, relative muscle mass and grip strength were high in rice bran diet groups. IL-6, TNF-α, MuRf-1, and atrogin-1 expression levels were lower, and Myog and GLUT4 were higher in the OHR group. Rice bran upregulated the expression of occludin and ZO-1 (gut tight junction proteins). The abundance of Akkermansiaceae in the cecum was relatively high in the OHR group. Our finding revealed that rice bran supplementation ameliorated gut barrier dysfunction and gut dysbiosis and also maintained muscle mass by downregulating the expression of MuRf-1 and atrogin-1 (muscle atrophy-related factors) in HFD-fed OVX mice.

Percutaneous endoscopic lumbar discectomy versus open lumbar microdiscectomy for treating lumbar disc herniation: Using the survival analysis.

Objectives: This study compared the risk of symptomatic recurrent disc herniation and clinical outcomes of percutaneous endoscopic lumbar discectomy (PELD) versus open lumbar microdiscectomy (OLM) for lumbar disc herniation with 2 years of follow-up. Materials and Methods: We analyzed 23 patients who underwent PELD and 32 patients who underwent OLM for lumbar disc herniation. The numeric rating scale of back and leg pain, Oswestry Disability Index (ODI), and Roland-Morris Disability Questionnaire (RMDQ) were assessed before and at 12 and 24 months after the surgery. The wound pain and complications were also recorded. Survival analysis was performed to estimate the risk of symptomatic recurrent disc herniation. Results: In the comparison of groups, the reductions in back and leg pain, ODI, and RMDQ were not significantly different at 12 and 24 months. For patients who underwent PELD, the wound pain was significant lower at the day of surgery. The survival rate of patients who were free from symptomatic recurrent disc herniation at 24 months was 0.913 in PELD and 0.875 in OLM, and the log-rank test revealed no significant difference between the two survival curves. The incidence of complication was not significantly different between groups. Conclusion: Both PELD and OLM are effective treatments for lumbar disc herniation because they have similar clinical outcomes. PELD provided patients with less painful wounds. The survival analysis revealed that the risk of symptomatic recurrent disc herniation in 2 years of follow-up was not different between PELD and OLM.

Microglia are involved in regulating histamine-dependent and non-dependent itch transmissions with distinguished signal pathways.

Although itch and pain have many similarities, they are completely different in perceptual experience and behavioral response. In recent years, we have a deep understanding of the neural pathways of itch sensation transmission. However, there are few reports on the role of non-neuronal cells in itch. Microglia are known to play a key role in chronic neuropathic pain and acute inflammatory pain. It is still unknown whether microglia are also involved in regulating the transmission of itch sensation. In the present study, we used several kinds of transgenic mice to specifically deplete CX3CR1+ microglia and peripheral macrophages together (whole depletion), or selectively deplete microglia alone (central depletion). We observed that the acute itch responses to histamine, compound 48/80 and chloroquine were all significantly reduced in mice with either whole or central depletion. Spinal c-fos mRNA assay and further studies revealed that histamine and compound 48/80, but not chloroquine elicited primary itch signal transmission from DRG to spinal Npr1- and somatostatin-positive neurons relied on microglial CX3CL1-CX3CR1 pathway. Our results suggested that microglia were involved in multiple types of acute chemical itch transmission, while the underlying mechanisms for histamine-dependent and non-dependent itch transmission were different that the former required the CX3CL1-CX3CR1 signal pathway.

How recreational farm operators use dynamic capabilities to respond to COVID-19 pandemic.

The outbreak of the COVID-19 Pandemic has devastated economic activities around the world. The tourism industry is facing severe challenges, such as reduced tourist flow and the lack of tourist consumption at destinations. Recreational farms are one of the business types of agricultural tourism in Taiwan and have the characteristics of small and medium-sized agriculture businesses. The operator is facing an uncertain environment in the epidemic market, and the operator's dynamic capability is considered to be effective in coping with the current environment. In this study, 20 selected recreational farms were interviewed to explore how operators use dynamic capabilities to make responses. The results show that recreational farms have the three elements of dynamic capabilities: sense, seize, and transform, to change farm marketing channels and develop new products or services to respond to the new market. Recreational farm operators adopted resource optimization, computerization, and cost control strategies to respond to the market. Management implications: A successful implementation of recreational farm offers requires-the reallocation of resources,-the planning of new products and services, and - the improvement of service processes to create new business and to address additional target groups.The COVID-19 pandemic forces a systematic positioning or repositioning of the business.

"DNA signaturing" database construction for Tetradesmus species identification and phylogenetic relationships of Scenedesmus-like green microalgae (Scenedesmaceae, Chlorophyta).

Species identification of Scenedesmus-like microalgae, comprising Desmodesmus, Tetradesmus, and Scenedesmus, has been challenging due to their high morphological and genetic similarity. After developing a DNA signaturing tool for Desmodesmus identification, we built a DNA signaturing database for Tetradesmus. The DNA signaturing tool contained species-specific nucleotide sequences of Tetradesmus species or strain groups with high similarity in ITS2 sequences. To construct DNA signaturing, we collected data on ITS2 sequences, aligned the sequences, organized the data by ITS2 sequence homology, and determined signature sequences according to hemi-compensatory base changes (hCBC)/CBC data from previous studies. Four Tetradesmus species and 11 strain groups had DNA signatures. The signature sequence of the genus Tetradesmus, TTA GAG GCT TAA GCA AGG ACCC, recognized 86% (157/183) of the collected Tetradesmus strains. Phylogenetic analysis of Scenedesmus-like species revealed that the Tetradesmus species were monophyletic and closely related to each other based on branch lengths. Desmodesmus was suggested to split into two subgenera due to their genetic and morphological distinction. Scenedesmus must be analyzed along with other genera of the Scenedesmaceae family to determine their genetic relationships. Importantly, DNA signaturing was integrated into a database for identifying Scenedesmus-like species through BLAST.

Characteristics and research status among clinical trials in cardio-oncology by bibliometric and visualized analysis.

BACKGROUND: We aim to establish the characteristics of published cardio-oncology research of clinical trials by bibliometric analysis and to talk about the prospects and difficulties facing the development of cardio-oncology. METHODS: Search of data related to clinical trials in cardiac oncology from 1990 to 2022 from the Web of Science core collection. Using CiteSpace to perform co-citation analysis of authors, countries (regions) and institutions, journals and cited journals, cited authors and cited literature, and keywords. RESULTS: Of the 607 clinical trial studies, the number of papers published per year has increased over time. The regions with the greatest influence were North America (especially the United States) and Europe. Multicenter research has always been the focus of cardio-oncology research, but cross-regional cooperation was still lacking. Myocardial toxicity caused by anthracyclines has received the earliest attention and has been studied for the longest time. Meanwhile, the efficacy and cardiotoxicity of new anticancer drugs always came into focus, but at a slow pace. Few studies on myocardial toxicity were related to the treatment of tumors except breast cancer. Risk factors, heart disease, adverse outcomes, follow-up, and intervention protection were the major hotspots revealed by co-citation cluster. CONCLUSIONS: There is great potential for the development of clinical trials in cardio-oncology, especially in multicenter cooperation across different regions. Expansion of tumor types, myocardial toxicity of different drugs, and effective interventions in the research direction and design of clinical trials are necessary.

RANKL Promotes Chemotherapy Resistance in Breast Cancer Cells Through STAT3 Mediated Autophagy Induction.

BACKGROUND: This study was to investigate the functional role and mechanism of receptor activator of nuclear factor-kappa B ligand (RANKL) associated autophagy and chemoresistance in breast cancer. MATERIALS AND METHODS: Cell Counting Kit-8 (CCK-8) assay was used to detect the cell viability. Real-time polymerase chain reaction (PCR) was used for determining the relative mRNA levels of key genes and protein expression was assessed by Western blotting. Immunofluorescence was performed to evaluate the changes in the autophagy flux. Short hairpin (shRNA) was used to knockdown the expression of the target genes in breast cancer cells. Based on The Cancer Genome Atlas (TCGA) database, we explored the expression of receptor activator of nuclear factor-kappa B (RANK), autophagy and signal transducer and activator of transcription 3 (STAT3) signaling associated genes and analyzed their correlation with the prognosis of breast cancer patients. RESULTS: The findings showed that receptor activator of nuclear factor-kappa B ligand (RANKL), the ligand of RANK, could effectively enhance the chemoresistance potential of breast cancer cells. Our results showed that RANKL induced autophagy and enhanced the expression of autophagy associated genes in breast cancer cells. The knockdown of RANK suppressed RANKL mediated autophagy induction in these cells. Furthermore, the inhibition of autophagy suppressed RANKL mediated chemoresistance in breast cancer cells. We found STAT3 signaling pathway was involved in RANKL-induced autophagy. Analysis of the expression of RANK, and autophagy and STAT3 signaling associated genes in breast cancer tissues showed that the expression of autophagy and STAT3 signaling associated genes was correlated with the prognosis of breast cancer patients. CONCLUSION: The present study suggests that the RANKL/RANK axis may potentially mediate chemoresistance in breast cancer cells by inducing autophagy through the STAT3 signaling pathway.

Influence of land-sea breeze on PM[Formula: see text] prediction in central and southern Taiwan using composite neural network.

PM[Formula: see text] prediction plays an important role for governments in establishing policies to control the emission of excessive atmospheric pollutants to protect the health of citizens. However, traditional machine learning methods that use data collected from ground-level monitoring stations have reached their limit with poor model generalization and insufficient data. We propose a composite neural network trained with aerosol optical depth (AOD) and weather data collected from satellites, as well as interpolated ocean wind features. We investigate the model outputs of different components of the composite neural network, concluding that the proposed composite neural network architecture yields significant improvements in overall performance compared to each component and the ensemble model benchmarks. The monthly analysis also demonstrates the superiority of the proposed architecture for stations where land-sea breezes frequently occur in the southern and central Taiwan in the months when land-sea breeze dominates the accumulation of PM[Formula: see text].

Using satellite data on remote transportation of air pollutants for PM2.5 prediction in northern Taiwan.

Accurate PM2.5 prediction is part of the fight against air pollution that helps governments to manage environmental policy. Satellite Remote sensing aerosol optical depth (AOD) processed by The Multi-Angle Implementation of Atmospheric Correlation (MAIAC) algorithm allows us to observe the transportation of remote pollutants between regions. The paper proposes a composite neural network model, the Remote Transported Pollutants (RTP) model, for such long-range pollutant transportation that predicts more accurate local PM2.5 concentrations given such satellite data. The proposed RTP model integrates several deep learning components and learns from the heterogeneous features of various domains. We also detected remote transportation pollution events (RTPEs) at two reference sites from the AOD data. Extensive experiments using real-world data show that the proposed RTP model outperforms the base model that does not account for RTPEs by 17%-30%, 23%-26% and 18%-22% and state-of-the-art models that account for RTPEs by 12%-22%, 12%-14%, and 10%-11% at +4h to +24h, +28h to +48 hours, and +52h to +72h hours respectively.

SLAC microresonator RF (SMuRF) electronics: A tone-tracking readout system for superconducting microwave resonator arrays.

We describe the newest generation of the SLAC Microresonator RF (SMuRF) electronics, a warm digital control and readout system for microwave-frequency resonator-based cryogenic detector and multiplexer systems, such as microwave superconducting quantum interference device multiplexers (µmux) or microwave kinetic inductance detectors. Ultra-sensitive measurements in particle physics and astronomy increasingly rely on large arrays of cryogenic sensors, which in turn necessitate highly multiplexed readout and accompanying room-temperature electronics. Microwave-frequency resonators are a popular tool for cryogenic multiplexing, with the potential to multiplex thousands of detector channels on one readout line. The SMuRF system provides the capability for reading out up to 3328 channels across a 4-8 GHz bandwidth. Notably, the SMuRF system is unique in its implementation of a closed-loop tone-tracking algorithm that minimizes RF power transmitted to the cold amplifier, substantially relaxing system linearity requirements and effective noise from intermodulation products. Here, we present a description of the hardware, firmware, and software systems of the SMuRF electronics, comparing achieved performance with science-driven design requirements. In particular, we focus on the case of large-channel-count, low-bandwidth applications, but the system has been easily reconfigured for high-bandwidth applications. The system described here has been successfully deployed in lab settings and field sites around the world and is baselined for use on upcoming large-scale observatories.

Cholic acid exposure during late pregnancy causes placental dysfunction and fetal growth restriction by reactive oxygen species-mediated activation of placental GCN2/eIF2α pathway.

Epidemiological studies suggest that fetal growth restriction (FGR) caused by gestational cholestasis is associated with elevated serum cholic acid (CA). Here, we explore the mechanism by which CA induces FGR. Pregnant mice except controls were orally administered with CA daily from gestational day 13 (GD13) to GD17. Results found that CA exposure decreased fetal weight and crown-rump length, and increased the incidence of FGR in a dose-dependent manner. Furthermore, CA caused placental glucocorticoid (GC) barrier dysfunction via down-regulating the protein but not the mRNA level of placental 11ß-Hydroxysteroid dehydrogenase-2 (11ß-HSD2). Additionally, CA activated placental GCN2/eIF2α pathway. GCN2iB, an inhibitor of GCN2, significantly inhibited CA-induced down-regulation of 11ß-HSD2 protein. We further found that CA caused excessive reactive oxygen species (ROS) production and oxidative stress in mouse placentas and human trophoblasts. NAC significantly rescued CA-induced placental barrier dysfunction by inhibiting activation of GCN2/eIF2α pathway and subsequent down-regulation of 11ß-HSD2 protein in placental trophoblasts. Importantly, NAC rescued CA-induced FGR in mice. Overall, our results suggest that CA exposure during late pregnancy induces placental GC barrier dysfunction and subsequent FGR may be via ROS-mediated placental GCN2/eIF2α activation. This study provides valuable insight for understanding the mechanism of cholestasis-induced placental dysfunction and subsequent FGR.

Antidepressive mechanisms of rhynchophylline in mice with chronic unpredictable stress-induced depression.

ETHNOPHARMACOLOGICAL RELEVANCE: Uncaria rhynchophylla ([Mi] Jack) (gouteng) exerts antidepressive effects. Rhynchophylline (RH), a major component of U. rhynchophylla, exerts similar pharmacological effects to those of gouteng. Thus, RH may have antidepressive effects. AIM OF THE STUDY: To investigate the anti-depressive effects of RH in chronic unpredictable mild stress (CUMS)-induced depressive mice. The anti-depressive mechanism of RH determined by measuring the 5-HT levels, the expressions of cAMP-response element binding protein (CREB) and brain-derived neurotrophic factor (BDNF) in cortex and hippocampus. MATERIALS AND METHODS: The behaviors of CUMS-induced depressive mice were measured using an open field test (OFT), forced swimming test (FST), and tail suspension test (TST). 5-HT levels were measured using an ELISA kits. The expressions of BDNF and CREB were determined using western blot test. RESULTS: RH increased the frequency of rearing and grooming in the OFT and decreased the immobility time in the FST and TST. RH effectively increased the 5-HT level and BDNF and CREB expressions in the cortex and hippocampus. CONCLUSION: Our findings indicate that the antidepressive mechanism of RH is related to increased levels of 5-HT from regulating CREB and BDNF expressions in cortex and hippocampus.

Development of a specific and sensitive diagnostic PCR for rapid molecular authentication of the medicinal plant Portulaca oleracea.

Adulteration by Bacopa monnieri (BM) in Portulaca oleracea (PO) plants frequently occurs; it decreases the efficacy of traditional Chinese medicine (TCM) and leads to fraud in the herbal marketplace. In this study, a diagnostic PCR assay was established for the rapid authentication of PO and BM in the herbal market. The sequence divergences in internal transcribed spacer 2 (ITS2) between PO and its adulterant species were used to design diagnostic PCR primers. The specific designed primer sets were evaluated and show that the diagnostic PCR assay can be used to verify the authenticity of PO and BM. The detection limits of the primer set for PO and BM identification were 10 pg and 1 pg, respectively. The reactivity of diagnostic PCR was 0.1% PO genomic DNA and 0.01% BM genomic DNA in the test sample during DNA amplification. In addition, multiplex PCR (mPCR) for PO and BM identification was also established. The samples were more susceptible to the effect of steaming in authentication by singleplex PCR and mPCR than boiling and drying treatment. Furthermore, commercial samples from the market were used to demonstrate the applicability of the developed diagnostic PCR for PO authentication and diagnose BM adulteration, and the investigation found that approximately 72.2% (13/18) of PO plants in the herbal market were adulterated. In conclusion, the diagnostic PCR assay was successfully developed and its specificity, sensitivity and reactivity for PO and BM authentication were proven. These developed PCR-based molecular methods can be applied as an identification tool for PO authenticity and can be practically applied for inspection of BM adulteration in the herbal market in the future.

Hepatotoxicity and mechanism of Rhododendri Mollis Flos based on zebrafish model / 中国中药杂志

This study used the zebrafish model to explore the hepatotoxicity of Rhododendri Mollis Flos(RMF). The mortality was calculated according to the number of the survival of zebrafish larvae 4 days after fertilization under different concentration of RMF, and the dose-toxicity curve was fitted to preliminarily evaluate the toxicity of RMF. The liver phenotypes under the sublethal concentration of RMF in the treatment group and the blank control group were observed by hematoxylin-eosin(HE) staining and acridine orange(AO) staining. Meanwhile, the activities of alanine aminotransferase(ALT) and aspartate aminotransferase(AST) were determined to confirm the hepatotoxicity of RMF. Real-time quantitative polymerase chain reaction(real-time PCR) and Western blot were used to determine the expressions of genes and proteins in zebrafish larvae. Gas chromatography time-of-flight mass spectrometry(GC-TOF-MS) was used to conduct untargeted metabolomics testing to explore the mechanism. The results showed that the toxicity of RMF to zebrafish larvae was dose-dependent, with 1 100 μg·mL~(-1) of the absolute lethal concentration and 448 μg·mL~(-1) of sublethal concentration. The hepatocyte apoptosis and degeneration appeared in the zebrafish larvae under the sublethal concentration of RMF. The content of ALT and AST in zebrafish larvae at the end of the experiment was significantly increased in a dose-dependent manner. Under the sublethal concentration, the expressions of genes and proteins related to apoptosis in zebrafish larvae were significantly increased as compared with the blank control group. The results of untargeted metabolomics showed that the important metabolites related to the he-patotoxicity of RMF were mainly enriched in alanine, aspartic acid, glutamic acid, and other pathways. In conclusion, it is inferred that RMF has certain hepatotoxicity to zebrafish larvae, and its mechanism may be related to apoptosis.