Correction: An E-selectin targeting and MMP-2-responsive dextran-curcumin polymeric prodrug for targeted therapy of acute kidney injury.

Correction for 'An E-selectin targeting and MMP-2-responsive dextran-curcumin polymeric prodrug for targeted therapy of acute kidney injury' by Jing-Bo Hu et al., Biomater. Sci., 2018, 6, 3397-3409, https://doi.org/10.1039/C8BM00813B.

[Quality status of Bombyx Batryticatus and suggestions for Chinese Pharmacopoeia (2025)].

To understand the current quality status and rearing situation of Bombyx Batryticatus, the authors collected 102 batches of Bombyx Batryticatus from different main producing areas and five major Chinese medicine markets from 2016 to 2018, and measured the properties and quality of the silk gland, to clarify the quality status of Bombyx Batryticatus from different producing areas and markets. In addition, 35 batches of Bombyx Batryticatus from 2019 to 2022 were used to verify the silk gland after revision. Moreover, Beauveria Bassiana was inoculated in the silkworm of 4-5 instars, and standardized rearing was carried out until they die. The death rate and the quality of Bombyx Batryticatus were measured to determine the differences in Bombyx Batryticatus of different instars, and explore the rationality of the infection age of Bombyx Batryticatus in Chinese Pharmacopoeia(2020). The results revealed that in the 102 batches of Bombyx Batryticatus, the qualification rate of silk gland was low; the content of total ash far exceeded the standard; the content of beauvericin varied greatly. The qualification rate of the silk gland of the 35 batches of Bombyx Batryticatus was only 47.49%, which could be increased to 73.00% if the number of silk gland was 2 to 4. The death rate of Bombyx Batryticatus at different infection ages was quite different, with uneven quality. Generally, the yield of Bombyx Batryticatus inoculated on the first day of the fifth instar was high with good quality. Therefore, in combination with the quality and actual production of Bombyx Batryticatus, the following suggestions were proposed for revision of Bombyx Batryticatus in Chinese Pharmacopoeia(2025): The number of silk gland should be revised as 2-4 bright brown or bright black silk glands, after which, the quality of Bombyx Batryticatus could be guaranteed, and the "quality identification based on character" could also be reflected scientifically; the content determination index that the content of beauvericin shall not be less than 0.017% should be added to better control the quality of Bombyx Batryticatus; the infection age should be revised as the first day of the fifth instar to narrow the age span, which could better fit the actual production and ensure the quality of Bombyx Batryticatus.

NRF-2/HO-1 Pathway-Mediated SHOX2 Activation Is a Key Switch for Heart Rate Acceleration by Yixin-Fumai Granules.

Population aging has led to increased sick sinus syndrome (SSS) incidence; however, no effective and safe medical therapy has been reported thus far. Yixin-Fumai granules (YXFMs), a Chinese medicine granule designed for bradyarrhythmia treatment, can effectively increase SSS patients' heart rate. Senescence-induced sinoatrial node (SAN) degeneration is an important part of SSS pathogenesis, and older people often show high levels of oxidative stress; reactive oxygen species (ROS) accumulation in the SAN causes abnormal SAN pacing or conduction functions. The current study observed the protective effects of YXFMs on senescent SAN and explored the relationship between the NRF-2/HO-1 pathway, SHOX2, and T-type calcium channels. We selected naturally senescent C57BL/6 mice with bradycardia to simulate SSS; electrocardiography, Masson's trichrome staining, and DHE staining were used to assess SAN function and tissue damage. Immunofluorescence staining and Western blotting were used to assay related proteins. In vitro, we treated human-induced pluripotent stem cell-derived atrial myocytes (hiPSC-AMs) and mouse atrial myocyte-derived cell line HL-1 with D-galactose to simulate senescent SAN-pacemaker cells. CardioExcyte96 was used to evaluate the pulsatile function of the hiPSC-AMs, and the mechanism was verified by DCFH-DA, immunofluorescence staining, RT-qPCR, and Western blotting. The results demonstrated that YXFMs effectively inhibited senescence-induced SAN hypofunction, and this effect possibly originated from scavenging of ROS and promotion of NRF-2, SHOX2, and T-type calcium channel expression. In vitro experiment results indicated that ML385, si-SHOX2, LDN193189, and Mibefradil reversed YXFMs' effects. Moreover, we, for the first time, found that ROS accumulation may hinder SHOX2 expression; YXFMs can activate SHOX2 through the NRF-2/HO-1 pathway-mediated ROS scavenging and then regulate CACNA1G through the SHOX2/BMP4/GATA4/NKX2-5 axis, improve T-type calcium channel function, and ameliorate the SAN dysfunction. Finally, through network pharmacology and molecular docking, we screened for the most stable YXFMs compound that docks to NRF-2, laying the foundation for future studies.

Tanshinone IIA improves contextual fear- and anxiety-like behaviors in mice via the CREB/BDNF/TrkB signaling pathway.

Posttraumatic stress disorder (PTSD) is one of the most common psychiatric diseases, which is characterized by the typical symptoms such as re-experience, avoidance, and hyperarousal. However, there are few drugs for PTSD treatment. In this study, conditioned fear and single-prolonged stress were employed to establish PTSD mouse model, and we investigated the effects of Tanshinone IIA (TanIIA), a natural product isolated from traditional Chinese herbal Salvia miltiorrhiza, as well as the underlying mechanisms in mice. The results showed that the double stress exposure induced obvious PTSD-like symptoms, and TanIIA administration significantly decreased freezing time in contextual fear test and relieved anxiety-like behavior in open field and elevated plus maze tests. Moreover, TanIIA increased the spine density and upregulated synaptic plasticity-related proteins as well as activated CREB/BDNF/TrkB signaling pathway in the hippocampus. Blockage of CREB remarkably abolished the effects of TanIIA in PTSD model mice and reversed the upregulations of p-CREB, BDNF, TrkB, and synaptic plasticity-related protein induced by TanIIA. The molecular docking simulation indicated that TanIIA could interact with the CREB-binding protein. These findings indicate that TanIIA ameliorates PTSD-like behaviors in mice by activating the CREB/BDNF/TrkB pathway, which provides a basis for PTSD treatment.

Association Between Plasma Vitamin D2 and Type 2 Diabetes Mellitus.

Objective: To investigate the relationship between plasma vitamin D2(VD2) and type 2 diabetes(T2DM). Method: Data from electronic medical records of 797 inpatients treated at Sun Yat Sen Memorial Hospital, Sun Yat-sen University between June 24, 2019 and December 24, 2020 were collected, and a total of 596 patients were enrolled after screening based on inclusion and exclusion criteria. Patients were divided into diabetic and non-diabetic groups according to whether they had T2DM. The Wilcoxon rank sum test was finally selected for the analysis of differences between groups according to the distribution of patients' plasma VD2, and logistic regression models were used to find the corresponding influencing factors. Result: Of the 596 hospitalized patients, 138 (23.15%) were diagnosed with T2DM. The Wilcoxon test showed no statistically significant difference in plasma VD2 concentrations between the T2DM and non-T2DM groups (p=0.833). After adjustment for confounders by multivariate logistic regression, there was still no significant difference in plasma VD2 concentrations between the two groups (P=0.316, OR: 1.15 (0.88,1.49)). The uncorrelated relationship between VD2 and T2DM was not found to change after incorporating 12 indicators, including demographic characteristics, laboratory indicators and complications, into the logistic regression model by 3 steps, even the OR (1.08 (0.92,1.26)) did not change in the 3 models. Similarly, the adjusted ORs agreed that there was no statistical association between VD2 and T2DM. Conclusion: VD2 levels are similar in patients with T2DM compared to those without T2DM. Clinical caution should be exercised in giving VD2 supplementation to patients with T2DM unless other diseases requiring VD2 supplementation (e.g., rickets, osteoporosis) are present.

Research on Data Analysis Network of TCM Tongue Diagnosis Based on Deep Learning Technology.

The aim of the study is to build a tongue image intelligent analysis "end-to-end" deep learning network based on a tongue diagnosis image of traditional Chinese medicine. The tongue target region in the original image was segmented by the UNet tongue segmentation model at the front end of the network. After segmentation, the feature vector of the tongue target region was extracted by the ResNet network, and then the blood pressure on the day of shooting was fused with the feature vector extracted by the ResNet network through the convolution operation method to complete the extraction of two groups of data of tongue feature and fusion feature. Based on analyzing the data of blood pressure, tongue image, and their fusion at the end of the network, four regression analysis methods were used to predict the stage mean value. After training, the model is tested with the test set data, and the test results are evaluated with mean absolute error (MAE). The prediction error of the model based on the fusion data of tongue image and blood pressure on the day of shooting was lower than that of the other two data modes. The UNet tongue segmentation model combined with the ResNet network can realize the automatic extraction of tongue image features. The extracted features combined with machine learning modeling can be used to explore the complex hierarchical mathematical association between tongue image and clinical data. The experimental results show that the multimodal data fusion method is an important way to mine the clinical value of the TCM tongue image.

Effect of Suanzaoren Decoction on molecular levels of bile acids in serum, liver, and ileum of insomnia mice / 中国中药杂志

To explore the mechanism of Suanzaoren Decoction in the treatment of insomnia from endogenous bile acid regulation, the present study investigated the hepatoprotective effect of Suanzaoren Decoction and the molecular changes of bile acids in the serum, liver, and ileum of insomnia model mice and Suanzaoren Decoction treated mice. The insomnia model in mice was established by the sleep deprivation method. After Suanzaoren Decoction(48.96 mg·kg~(-1)·d~(-1)) intervention by gavage for 7 days, the related indicators, such as water consumption, food intake, body weight, aspartate aminotransferase(AST), alanine transaminase(ALT), and total bile acid(TBA) were detected, and the pathological changes of the liver and ileum were observed. The molecular levels and distribution of 23 bile acids in the serum, liver, and ileum were analyzed by UPLC-MS/MS combined with principal component analysis(PCA) and partial least squares discriminant analysis(PLS-DA). The results showed that Suanzaoren Decoction could improve the decreased water consumption and food intake, weight loss, and increased AST and ALT in the model group, and effectively reverse the injury and inflammation in the liver and ileum. The bile acids in the liver of the insomnia model mice were in the stage of decompensation, and the bile acids in the serum, liver, and ileum of the mice decreased or increased. Suanzaoren Decoction could regulate the anomaly of some bile acids back to normal. Seven bile acids including glycoursodeoxycholic acid(GUDCA), glycodesoxycholic acid(GDCA), tauro-α-MCA(T-α-MCA), α-MCA, taurodeoxycholate(TDCA), T-β-MCA, and LCA were screened out as the main discriminant components by PLS-DA. It is concluded that Suanzaoren Decoction possesses the hepatoprotective effect and bile acids could serve as the biochemical indicators to evaluate the drug efficacy in the treatment of abnormal liver functions caused by insomnia. The mechanism of Suanzao-ren Decoction in soothing the liver, resolving depression, tranquilizing the mind, and improving sleep may be related to the molecular regulation of bile acid signals.

A Luminol-Based Self-Illuminating Nanocage as a Reactive Oxygen Species Amplifier to Enhance Deep Tumor Penetration and Synergistic Therapy.

The dense extracellular matrix (ECM) in tumor tissues resists drug diffusion into tumors and leads to a poor prognosis. To address this problem, glucose oxidase (GOx)-modified ferritin loaded with luminol-curcumin was fabricated. Once delivered to the tumor, this luminol-based self-illuminating nanocage could actively convert glucose to reactive oxygen species (ROS) to achieve starvation therapy. Then, excessive ROS were transmitted to luminol, thereby emitting 425 nm blue-violet light. Momentarily, light was further absorbed by curcumin and ROS production was amplified. Abundant ROS helps break down the ECM network to penetrate deep into tumors. In addition, ROS produced after cell internalization can induce apoptosis of tumor cells by decreasing the mitochondrial membrane potential and can promote ferroptosis by consuming reduced glutathione. Effective penetration and multiple pathways inducing tumor cell death contributed to the efficient antitumor effect (tumor inhibition rate of GOx-modified ferritin loaded with luminol-curcumin: 71.73%). This study developed a glucose-driven self-illuminating nanocage for active tumor penetration via ROS-mediated destruction of the ECM and provided the synergetic mechanism of apoptosis and ferroptosis.

Synergistic effect of tumor chemo-immunotherapy induced by leukocyte-hitchhiking thermal-sensitive micelles.

Some specific chemotherapeutic drugs are able to enhance tumor immunogenicity and facilitate antitumor immunity by inducing immunogenic cell death (ICD). However, tumor immunosuppression induced by the adenosine pathway hampers this effect. In this study, E-selectin-modified thermal-sensitive micelles are designed to co-deliver a chemotherapeutic drug (doxorubicin, DOX) and an A2A adenosine receptor antagonist (SCH 58261), which simultaneously exhibit chemo-immunotherapeutic effects when applied with microwave irradiation. After intravenous injection, the fabricated micelles effectively adhere to the surface of leukocytes in peripheral blood mediated by E-selectin, and thereby hitchhiking with leukocytes to achieve a higher accumulation at the tumor site. Further, local microwave irradiation is applied to induce hyperthermia and accelerates the release rate of drugs from micelles. Rapidly released DOX induces tumor ICD and elicits tumor-specific immunity, while SCH 58261 alleviates immunosuppression caused by the adenosine pathway, further enhancing DOX-induced antitumor immunity. In conclusion, this study presents a strategy to increase the tumor accumulation of drugs by hitchhiking with leukocytes, and the synergistic strategy of chemo-immunotherapy not only effectively arrested primary tumor growth, but also exhibited superior effects in terms of antimetastasis, antirecurrence and antirechallenge.

Brain structural alterations in MDD patients with gastrointestinal symptoms: Evidence from the REST-meta-MDD project.

OBJECTIVE: While gastrointestinal (GI) symptoms are very common in patients with major depressive disorder (MDD), few studies have investigated the neural basis behind these symptoms. In this study, we sought to elucidate the neural basis of GI symptoms in MDD patients by analyzing the changes in regional gray matter volume (GMV) and gray matter density (GMD) in brain structure. METHOD: Subjects were recruited from 13 clinical centers and categorized into three groups, each of which is based on the presence or absence of GI symptoms: the GI symptoms group (MDD patients with at least one GI symptom), the non-GI symptoms group (MDD patients without any GI symptoms), and the healthy control group (HCs). Structural magnetic resonance images (MRI) were collected of 335 patients in the GI symptoms group, 149 patients in the non-GI symptoms group, and 446 patients in the healthy control group. The 17-item Hamilton Depression Rating Scale (HAMD-17) was administered to all patients. Correlation analysis and logistic regression analysis were used to determine if there was a correlation between the altered brain regions and the clinical symptoms. RESULTS: There were significantly higher HAMD-17 scores in the GI symptoms group than that of the non-GI symptoms group (P < 0.001). Both GMV and GMD were significant different among the three groups for the bilateral superior temporal gyrus, bilateral middle temporal gyrus, left lingual gyrus, bilateral caudate nucleus, right Fusiform gyrus and bilateral Thalamus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the HC group, the GI symptoms group demonstrated increased GMV and GMD in the bilateral superior temporal gyrus, and the non-GI symptoms group demonstrated an increased GMV and GMD in the right superior temporal gyrus, right fusiform gyrus and decreased GMV in the right Caudate nucleus (GRF correction, cluster-P < 0.01, voxel-P < 0.001). Compared to the non-GI symptoms group, the GI symptoms group demonstrated significantly increased GMV and GMD in the bilateral thalamus, as well as decreased GMV in the bilateral superior temporal gyrus and bilateral insula lobe (GRF correction, cluster-P < 0.01, voxel-P < 0.001). While these changed brain areas had significantly association with GI symptoms (P < 0.001), they were not correlated with depressive symptoms (P > 0.05). Risk factors for gastrointestinal symptoms in MDD patients (p < 0.05) included age, increased GMD in the right thalamus, and decreased GMV in the bilateral superior temporal gyrus and left Insula lobe. CONCLUSION: MDD patients with GI symptoms have more severe depressive symptoms. MDD patients with GI symptoms exhibited larger GMV and GMD in the bilateral thalamus, and smaller GMV in the bilateral superior temporal gyrus and bilateral insula lobe that were correlated with GI symptoms, and some of them and age may contribute to the presence of GI symptoms in MDD patients.

Yixin-Fumai granules improve sick sinus syndrome in aging mice through Nrf-2/HO-1 pathway: A new target for sick sinus syndrome.

ETHNOPHARMACOLOGICAL RELEVANCE: Yixin-Fumai granules (YXFMs)-composed of Ginseng quinquefolium (L.) Alph. Wood, Ophiopogon japonicus (Thunb.) Ker Gawl, Schisandra arisanensis Hayata, Astragalus aaronsohnianus Eig, Salvia cryptantha Montbret & Aucher ex Benth, and Ligusticum striatum DC-are compound granules used in traditional Chinese medicine to increase heart rate and thus treat bradyarrhythmia. It may be effective in treating sick sinus syndrome (SSS). AIM: To observe the effect of YXFMs on aging-induced SSS in mice and explore whether this effect is related to the Nrf-2/HO-1 signaling pathway. MATERIALS AND METHODS: Mice with a significant decrease in the heart rate due to natural aging were selected to construct an SSS model. After the mice were administered YXFMs, the damage to their sinoartrial node (SAN) was assessed through electrocardiography, Masson's trichrome staining, and terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL). Dihydroethidium staining and immunofluorescence staining were used to assay reactive oxygen species (ROS) content and HCN4, respectively. Moreover, to observe the effects of YXFMs in vitro, the HL-1 cell line, derived from mouse atrial myocytes, was used to simulate SAN pacemaker cells, with H2O2 used as the cellular oxidative stress (OS) inducer. 2,7-Dichlorodihydrofluorescein diacetate staining was used to assay ROS content, whereas immunofluorescence staining and Western blotting were used to elucidate the related protein expression. Finally, mice were injected the Nrf-2 inhibitor ML385 to reversely verify the effects of YXFMs. RESULTS: In our in vivo experiments, YXFMs significantly inhibited aging-induced SSS, shortened the R-R interval, increased heart rate, alleviated fibrosis, reduced apoptosis rate and ROS content, and promote HCN4 expression in the SAN. In our in vitro experiments, YXFMs significantly inhibited H2O2-induced cell peroxidation damage, promoted Nrf-2 activation and nuclear metastasis, increased HO-1 expression- thereby inhibiting ROS accumulation-and finally, upregulated HCN4 expression through the inhibition of histone deacetylase 4 (HDAC4) expression and its nuclear metastasis. Finally, injection of the Nrf-2 inhibitor ML385 after YXFMs administration inhibited their protective effect in the mice. CONCLUSION: Here, we elaborated on the relationship between aging-induced SSS and the Nrf-2/HO-1 pathway for the first time and proposed that YXFMs improve SSS via the Nrf-2/HO-1 axis. Specifically, YXFMs promoted Nrf-2 activation and plasma-nuclear transfer to enhance HO-1 expression via the Nrf-2/HO-1 axis. This inhibited OS and reduced ROS accumulation in the SAN, and then, through the ROS/HDAC4 axis, reduced HDAC4 expression and plasma-nuclear transfer. Thereby, the OS-induced HCN4 loss in the SAN was inhibited-improving the function of If channel and thus producing SAN protection effect against SSS and improving the heart rate and R-R interval. In the future, we plan to use bioinformatics analysis technology to execute the next step of our research, namely to determine the effect of isolated, purified components of YXFMs in SSS, to increase its efficiency and reduce the toxicity of YXFMs.

Shenxian-Shengmai Oral Liquid Improves Sinoatrial Node Dysfunction through the PKC/NOX-2 Signaling Pathway.

Sick sinus syndrome (SSS) is one of the common causes of cardiac syncope and sudden death; the occurrence of SSS is associated with the accumulation of ROS in the sinoatrial node (SAN). Shenxian-shengmai (SXSM) is a traditional Chinese medicine available as oral liquid that causes a significant increase in heart rate. The objective of this study is to observe the improvement of SXSM on SAN function in SSS mice and explore its potential mechanism. In the current study, SSS was simulated in mice by inducing SAN dysfunction using a micro-osmotic pump to inject angiotensin II (Ang II). The mouse model with SSS was used to determine the effect of SXSM on SAN function and to explore its potential mechanism. Furthermore, the HL-1 cell line, derived from mouse atrial myocytes, was used to simulate SAN pacemaker cells. Our results indicated that SXSM significantly increased the heart rate of SSS mice by reducing the AngII-induced accumulation of ROS in the SAN and by inhibiting the expression of HDAC4, thereby reducing the loss of HCN4, a critical component of the cardiac conduction system. MASSON staining revealed a reduction of SAN damage in SSS mice that were treated with SXSM compared with controls. In vitro experiments showed that AngII treatment caused an upregulation of the PKC/NOX-2 signaling pathway in HL-1 cells which could be prevented by pretreatment with SXSM. The protective effect of SXSM was attenuated upon treatment with the PCK agonist PMA. In conclusion, SXSM reduced the AngII-induced accumulation of ROS in the SAN through the PKC/NOX2 signaling pathway, improving the functioning of the SAN and preventing the decrease of heart rate in SSS mice.

[Primary Study on Chronic Myeloid Leukemia in NCG Mice from Qinba Mushroom].

OBJECTIVE: The present study was to evaluate the anti-tumor effects of acidic RNA protein complex (FA-2-b-ß) extracted from the wild edible Qinba mushroom in inducing of apoptosis and immunoregulation of tumor cell. METHODS: Cell proliferation inducing rate of FA-2-b-ß to K562 cell was measured using CCK-8. Apoptosis rate was detected by using flow cytometry. Chronic myeloid leukemia model was developed by tail vein injection/subcutaneous inoculation of K562 cells in NCG mice. The tumor burden of mice was observed. The general condition of the mice was monitored twice daily. The peripherivcal full blood counts of mice was tested daily. RT-qPCR and Western blot was FA-2-b-ß performed to determine involvement of apoptotic-related gene and protenin, Immunofluorescence and immunohistochemistry was used to detected the expression of CD3, CD4 and CD8. RESULTS: The proliferation and apoptosis of K562 cell could be inhibitied and induced by FA-2-b-ß, there was 100% successful in the tumor formation in vivo, after treated by drug for 21 days there were significantly increased peripheral leucocytes, but decreased hemoglobin of mice treated by FA-2-b-ß as compared with those in control group. The CD3, CD4 and CD8 showed positive in mice, and the propotation was imbalance, but it showed reserved after treated by FA-2-b-ß. CONCLUSION: FA-2-b-ß is strong anti-leukemia effect in vitro and in vivo, suggesting the traditional Chinese medicine maybe contribute to the anti-cancer and immunoregulation research.

Selection of water source for water transfer based on algal growth potential to prevent algal blooms.

Water transfer is becoming a popular method for solving the problems of water quality deterioration and water level drawdown in lakes. However, the principle of choosing water sources for water transfer projects has mainly been based on the effects on water quality, which neglects the influence in the variation of phytoplankton community and the risk of algal blooms. In this study, algal growth potential (AGP) test was applied to predict changes in the phytoplankton community caused by water transfer projects. The feasibility of proposed water transfer sources (Baqing River and Jinsha River) was assessed through the changes in both water quality and phytoplankton community in Chenghai Lake, Southwest China. The results showed that the concentration of total nitrogen (TN) and total phosphorus (TP) in Chenghai Lake could be decreased to 0.52 mg/L and 0.02 mg/L respectively with the simulated water transfer source of Jinsha River. The algal cell density could be reduced by 60%, and the phytoplankton community would become relatively stable with the Jinsha River water transfer project, and the dominant species of Anabaena cylindrica evolved into Anabaenopsis arnoldii due to the species competition. However, the risk of algal blooms would be increased after the Baqing River water transfer project even with the improved water quality. Algae gained faster proliferation with the same dominant species in water transfer source. Therefore, water transfer projects should be assessed from not only the variation of water quality but also the risk of algal blooms.

Study on bile acid metabolism of sleep-deprived mice regulated by Jiaotai Pills based on LC-MS / 中国中药杂志

To investigate the changes of bile acid(BA) levels in mice with sleep deprivation and the regulatory effect of Jiaotai Pills(JTP) on bile acid metabolism, this study established an ultra-performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS) method for simultaneous determination of 23 BAs in mice. A total of 24 ICR mice were randomized into normal group, model group, and JTP group. Mice in the model group and JTP group were deprived of sleep at 20 h·d~(-1) by sleep deprivation apparatus for 8 consecutive days. Mice in the JTP group were given(ig, qd) JTP 3.3 g·kg~(-1) and those in the normal group and model group received(ig) the same volume of purified water. UPLC conditions are as follows: Waters ACQUITY UPLC BEH C_(18) column(2.1 mm×100 mm, 1.7 μm), gradient elution with the mobile phase of 0.1% formic acid in water-methanol. MS conditions are as below: negative-ion electrospray ionization, multiple reaction monitoring(MRM). Thereby, the content of 23 BAs in serum, liver, and ileum was determined and methodological investigation of the method was performed. The results showed that 23 BAs could be accurately determined within 15 min and the correlation coefficients were all higher than 0.99. The precision, accuracy, specificity, reproducibility, matrix effect, and recovery of BAs all met the requirement. The levels of BAs were significantly increased in the serum, liver, and ileum of sleep-deprived mice, but JTP can significantly reduce the levels. The UPLC-MS/MS method is simple, rapid, and accurate, which can be used for the determination of 23 BAs in biological samples, and JTP can adjust the elevated BA levels of sleep-deprived mice.

New phenylpropanoid-substituted and benzyl-substituted flavonols from Alangium chinense.

Two previously undescribed flavonols with phenylpropanoid or benzyl substitution, named alangsine A (1), and alangsine B (2), together with four known compounds (3-6) were isolated from the leaves of Alangium chinense. Alangsine A was a racemic mixture, which was further separated into two enantiomers via high-performance liquid chromatography on a chiral column. The absolute configurations of the enantiomer pairs were deduced from the circular dichroism (CD) spectra. The activity of the isolated compounds towards neuronal excitability was examined.

Orostachys japonicus ameliorates acetaminophen-induced acute liver injury in mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Orostachys japonicus A. Berger (O. japonicus), referred to as Wa-song in Korea is a traditional and herbal medicine. Even though it has been traditionally used to treat inflammation- and toxicity-related diseases, the effects of ethanol extract of O. japonicus (OJE) on acetaminophen (N-acetyl-p-aminophenol, APAP) overdose-induced hepatotoxicity have not been determined yet. AIM OF THE STUDY: The present study was aimed to investigate the effects of OJE against APAP-induced acute liver injury (ALI) and explore the underlying mechanisms. MATERIALS AND METHODS: Mice were treated orally with OJE (50, 100, or 200 mg/kg) for seven days before APAP (300 mg/kg) injection. After 12 h of APAP treatment, serum and liver tissues were collected. An in vitro system using primary hepatocytes was also applied in this study. RESULTS: Pretreatment with OJE, especially at a dose of 200 mg/kg, reduced APAP overdose-induced ALI in mice, as evidenced by decreased serum alanine/aspartate aminotransferase levels, histopathological damage, and inflammation. Consistently, OJE pretreatment reduced the gene transcription of cytochrome P450 (CYP) 3A11 and CYP1A2 in livers of mice injected with or without APAP, at least in part, via inactivation of nuclear receptor pregnane X receptor (PXR). Furthermore, the role of PXR in mediating the OJE regulation of CYPs was confirmed in primary hepatocytes, which showed that OJE pretreatment inhibited PXR activity and APAP hepatotoxicity enhanced by pregnenolone 16α-carbonitrile, a mouse agonist of PXR. Besides, the antioxidative activity provided by OJE, involving increases in hepatic glutathione (GSH) content and decreases in malondialdehyde levels, has been shown to exert hepatoprotective effects in normal and injured livers. Moreover, APAP-activated c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) in mice liver were indirectly inhibited by pretreatment with OJE. CONCLUSIONS: Taken together, our findings showed that OJE attenuated APAP-induced ALI by decreasing APAP-metabolizing enzymes via inactivation of PXR and the restoration of hepatic GSH content. Therefore, OJE could be a promising hepatoprotective agent.

The complete chloroplast genome sequence of medicinal plant, Artemisia Montana.

The complete chloroplast genome sequence of Artemisia montana was characterized from Illumina pair-end sequencing. The chloroplast genome of A. montana was 151,130 bp in length, containing a large single-copy region (LSC) of 80,975 bp, a small single-copy region (SSC) of 16,011 bp, and two inverted repeat (IR) regions of 27,162 bp. The overall GC content is 30.70%, while the correponding values of the LSC, SSC, and IR regions are 64.6%, 69.2%, and 60.1%, respectively. The genome contains 131 complete genes, including 86 protein-coding genes (62 protein-coding gene species), 37 tRNA genes (29 tRNA species) and 8 rRNA genes (4 rRNA species). The Neighbour-joining phylogenetic analysis showed that A. montana and Artemisia lavandulaefolia YC clustered together as sisters to other Artemisia species.

NIR-Triggered Sequentially Responsive Nanocarriers Amplified Cascade Synergistic Effect of Chemo-Photodynamic Therapy with Inspired Antitumor Immunity.

A desirable cancer therapeutic strategy is supposed to have effective ability to not only exert maximum anticancer ability but also inspire antitumor immunity for preventing tumor relapse and metastasis. During this research, multifunctional upconversion nanoparticles (UCNPs) coated by ROS-responsive micelles are prepared for tumor targeting and near-infrared (NIR)-triggered photodynamic therapy (PDT)-combined synergistic effect of chemotherapy. Moreover, both PDT and chemotherapy agents could activate antitumor immunity via inducing immunogenic cell death with CD8+ and CD4+ T cells infiltrating in tumors. Through the experiments, intravenous administration of multifunctional nanocarriers with noninvasive NIR irradiation destroys the orthotopic tumors and efficiently suppresses lung metastasis in a metastatic triple-negative breast cancer model by cascade-amplifying chemo-PDT and systemic antitumor immunity. In conclusion, this study provides prospective chemo-PDT with inspired antitumor immunity for metastatic cancer treatment.

The vascular dilatation induced by Hydroxysafflor yellow A (HSYA) on rat mesenteric artery through TRPV4-dependent calcium influx in endothelial cells.

ETHNOPHARMACOLOGICAL RELEVANCE: Hydroxysafflor yellow A (HSYA) is the principal constituent of the flowers of Carthamus tinctorius L., a traditional Chinese herbal medicine, which has been used for the treatment of cerebrovascular and cardiovascular diseases due to its property of promoting blood circulation and removing blood stasis. It is dominated in the water extract of Carthamus tinctorius L., which has been used in the clinical treatment for cardiovascular diseases. HSYA exerts a variety of pharmacological efficacy upon the vascular system. However, the underlying mechanisms remain unclear. AIM OF THE STUDY: To investigate the vascular dilatation effect of HSYA on rat mesenteric artery (MA) and its potential mechanism. MATERIALS AND METHODS: Adult male Wistar rats were applied to the study. Tension studies were conducted to determine the dilatation activity of HSYA against pre-contracted mesenteric arterial (MA) rings by U 46619 and Phenylephrine (PE). The vascular activities were measured with or without incubation with some selective inhibitors, including L-N(ω)-nitro-L-arginine methyl ester (L-NAME, a nitro oxide synthase inhibitor), HC-067047 (a selective TRPV4 antagonist), BaCl2 (a Kir channel blocker), and Indomethacin (Indo, a nonselective cyclooxygenase inhibitor), respectively. Immunocytochemistry, Calcium Imaging, NO Production detection, and Western Blot were also employed to further study the underlying mechanism. RESULTS: HSYA reversed the constriction of MAs induced by U 46619 in a manner of concentration dependency, and the dilatation capability was reversed by L-NAME. This effect was significantly dependent on the intactness of MA endothelium, accompanying an increment of NO production in mesenteric arterial endothelium cells. The increment of NO production was reversed by inhibiting the PKA. Also, the expression of p-eNOS was activated by HSYA shown in Western Blot assays. The cells imaging revealed a significant increase and drop of the influx of Ca2+ before and after treatment with HC-067047. CONCLUSIONS: These findings suggest that HSYA exerts vessel dilation effect on MAs via a TRPV4-dependent influx of Ca2+ in endothelium cells, PKA-dependent eNOS phosphorylation and NO production mechanism. The present study indicates that HSYA has the potential to be a future candidate for the treatment of hypertension.