Twelve-component pharmacokinetic study of rat plasma after oral administration of You-Gui-Wan in osteoporosis rats with kidney-yin deficiency and kidney-yang deficiency.

You-Gui-Wan is a widely used traditional Chinese medicine preparation for the treatment of osteoporosis with kidney-yang deficiency, and is composed of both yang-invigorating and kidney-tonifying herbs, and yin-nourishing and kidney essence-replenishing herbs. Considering that the pharmacokinetics of drugs might differ in different pathological conditions, it is necessary to study the pharmacokinetic characteristics of You-Gui-Wan under different osteoporotic conditions. In this study, the pharmacokinetic behaviors of You-Gui-Wan in osteoporosis rats with kidney-yin and kidney-yang deficiency were compared. The results showed that the absorption, metabolism, and disposition of You-Gui-Wan varied widely in animals with different types of osteoporosis. The active components belonging to the yang-invigorating herbs, such as aconitine, hypaconitine, mesaconitine, benzoylaconine, benzoylhypacoitine, benzoylmesaconine, chlorogenic acid and pinoresinol diglucoside, had a higher uptake and slower elimination in osteoporosis rats with kidney-yang deficiency, which corresponds to the opinion that You-Gui-Wan is used to treat kidney-yang deficiency syndrome, and indicates the scientific nature of Bian-Zheng-Lun-Zhi.

Comparative Pharmacokinetic Study of 5 Active Ingredients after Oral Administration of Zuogui Pill in Osteoporotic Rats with Different Syndrome Types.

Zuogui Pill is a kidney-yin-tonifying formula in traditional Chinese medicine that is widely used to manage osteoporosis with kidney-yin-deficiency in China. Herein, an efficient and accurate high-performance liquid chromatography-tandem mass spectrometry method was developed to determine the concentrations of 5 bioactive compounds in rat plasma following oral administration of Zuogui Pill. Because drug absorption and distribution differ under physiological and pathological conditions, the established method was used to quantify blood components and dynamic change in osteoporotic rats with different syndrome types. Moreover, integrated pharmacokinetic study was conducted to describe the overall pharmacokinetic characteristics of traditional Chinese medicine. The results showed that the absorption, distribution, and metabolism of Zuogui Pill varied widely under different states. The bioavailability of most active components showed significant advantages in osteoporotic rats with kidney-yin-deficiency, which corresponds to the opinion that Zuogui Pill has the effect of nourishing kidney-yin. It is hoped that this finding could interpret the pharmacodynamic substances and mechanism of Zuogui Pill in the treatment of osteoporosis with kidney-yin-deficiency.

Comparative pharmacokinetic study of nine bioactive components in osteoarthritis rat plasma using ultra-performance liquid chromatography-tandem mass spectrometry after single and combined oral administration of Epimedii Folium and Chuanxiong Rhizoma extracts.

The herb pair Epimedii Folium-Chuanxiong Rhizoma (EF-CR), derived from the classical traditional Chinese medicine 'Xian Ling Pi San', has a distinctive compatibility therapeutic profile and is clinically safe and effective. This study aimed to investigate and compare the pharmacokinetic characteristics of nine analytes in osteoarthritis (OA) rat plasma after the oral administration of EF, CR or a combination of these two herbs. We developed an ultra-performance liquid chromatography method coupled with quadrupole linear ion-trap mass spectrometry to simultaneously quantify and assess the pharmacokinetics of icariin, epimedin A, epimedin B, epimedin C, icariside I, icariside II, ferulic acid, ligustilide and senkyunolide A of the EF-CR pair in the plasma of osteoarthritic rats. The pharmacokinetic parameters showed that the absorption of multiple components was significantly enhanced and residence time was prolonged in the EF-CR group (P < 0.05) compared to the single-herb group. These parameters revealed that the combination of EF and CR exhibited synergistic effects of the nine bioactive components, suggesting the potential application of the EF-CR combination for the treatment of OA.

Supervised and Semisupervised Manifold Embedded Knowledge Transfer in Motor Imagery-Based BCI.

A long calibration procedure limits the use in practice for a motor imagery (MI)-based brain-computer interface (BCI) system. To tackle this problem, we consider supervised and semisupervised transfer learning. However, it is a challenge for them to cope with high intersession/subject variability in the MI electroencephalographic (EEG) signals. Based on the framework of unsupervised manifold embedded knowledge transfer (MEKT), we propose a supervised MEKT algorithm (sMEKT) and a semisupervised MEKT algorithm (ssMEKT), respectively. sMEKT only has limited labelled samples from a target subject and abundant labelled samples from multiple source subjects. Compared to sMEKT, ssMEKT adds comparably more unlabelled samples from the target subject. After performing Riemannian alignment (RA) and tangent space mapping (TSM), both sMEKT and ssMEKT execute domain adaptation to shorten the differences among subjects. During domain adaptation, to make use of the available samples, two algorithms preserve the source domain discriminability, and ssMEKT preserves the geometric structure embedded in the labelled and unlabelled target domains. Moreover, to obtain a subject-specific classifier, sMEKT minimizes the joint probability distribution shift between the labelled target and source domains, whereas ssMEKT performs the joint probability distribution shift minimization between the unlabelled target domain and all labelled domains. Experimental results on two publicly available MI datasets demonstrate that our algorithms outperform the six competing algorithms, where the sizes of labelled and unlabelled target domains are variable. Especially for the target subjects with 10 labelled samples and 270/190 unlabelled samples, ssMEKT shows 5.27% and 2.69% increase in average accuracy on the two abovementioned datasets compared to the previous best semisupervised transfer learning algorithm (RA-regularized common spatial patterns-weighted adaptation regularization, RA-RCSP-wAR), respectively. Therefore, our algorithms can effectively reduce the need of labelled samples for the target subject, which is of importance for the MI-based BCI application.

[Regulation of vascular endothelial cell activator expression by tanshinone â ¡_A based on PI3K/Akt signaling pathway].

The present study investigated the regulatory effect of tanshinone Ⅱ_A(TAⅡ_A) on activator expression in human umbilical vein endothelial cells(HUVECs) and the effect on the phosphoinositide 3-kinase(PI3 K)/protein kinase B(Akt) signaling pathway in patients with antiphospholipid syndrome(APS). HUVECs cultured in vitro were divided into a medium group, a blank control group, an APS model group, an APS+LY5 group, an APS+LY10 group, an APS+LY20 group, an APS+TAⅡ_A5 group, an APS+TAⅡ_A10 group, an APS+TAⅡ_A20 group, and an APS+TAⅡ_A10+LY10 group. The effects of LY294002 and TAⅡ_A at different concentrations on the secretion of interleukin-6(IL-6), interleukin-8(IL-8), and monocyte chemoattractant protein-1(MCP-1) by HUVECs were investigated. The effects on the mRNA expression of annexin A2(ANXA2), PI3 K, Akt, and E-cadherin(E-cad) were detected by quantitative polymerase chain reaction(qPCR), and Western blot was used to determine the effects on the protein expression of ANXA2, p-PI3 K/PI3 K, p-Akt/Akt, and E-cad. The results revealed that compared with the APS model group, the APS+TAⅡ_A10 group showed statistically reduced IL-6 and MCP-1 and increased IL-8 in a concentration-dependent manner with the increase in TAⅡ_A dose, while the APS+TAⅡ_A10 group showed increased mRNA and protein expression of ANXA2, PI3 K, Akt, and E-cad(P<0.05 or P<0.01) in a concentration-dependent manner with the increase in TAⅡ_A dose. The findings indicated that the serum of APS patients could lead to the decreased mRNA and protein expression levels of ANXA2, PI3 K, Akt, and E-cad in HUVECs, increased secretion of IL-6 and MCP-1, and reduced secretion of IL-8, and activate vascular endothelial cells. In contrast, once the PI3 K/Akt signaling pathway was blocked, the mRNA and protein expression of ANXA2 and E-cad significantly decreased, IL-6 and MCP-1 secretion significantly increased, and IL-8 secretion was significantly reduced. It suggests that TAⅡ_A regulates the activation of vascular endothelial cells in APS patients by activating the PI3 K/Akt signaling pathway.

MgO-loaded nitrogen and phosphorus self-doped biochar: High-efficient adsorption of aquatic Cu2+, Cd2+, and Pb2+ and its remediation efficiency on heavy metal contaminated soil.

In this study, the MgO-loaded fish scale biochar (MgO-FB) was synthesized by impregnation of MgCl2 using fish scales as precursor, and the modified biochar was applied for the adsorption of aquatic Cu2+, Cd2+, and Pb2+, and the immobilization of heavy metals in soils. The maximum adsorption capacities of MgO-FB for Cu2+, Cd2+, and Pb2+ were 505.8, 327.2, and 661.2 mg/g, respectively. In addition, MgO-FB can keep the excellent adsorption capacity under various environmental disturbances including pH, humic acid, and high ionic strength. Multiple characterizations and comparative experiments have demonstrated that the hydroxyapatite components and the MgO micro-nanoparticles on MgO-FB enhanced the adsorption capacity for Cu2+, Cd2+, and Pb2+ through ion-exchange and precipitation process. The metal-π electron coordination and complexation with oxygen-, nitrogen-, and phosphorus-containing groups were also responsible for the removal of heavy metal ions. Besides, MgO-FB also performed excellently for the immobilization of Cu, Cd, and Pb in soils, and the contents of available Cu, Cd, and Pb were reduced by 84.2%, 74.2%, and 53.7% respectively with the addition of MgO-FB. In general, these results show that waste fish scales co-pyrolysis with MgCl2 impregnation can be considered as a promising and efficient material for the remediation of heavy metal contaminated waters and soils.

HPLC-MS/MS based comparative pharmacokinetics of 12 bioactive components in normal and osteoporosis rats after oral administration of You-Gui-Wan.

You-Gui-Wan is a traditional Chinese patent medicine that has been extensively used to treat kidney-yang deficiency syndrome. An high-performance liquid chromatography tandem mass spectrometry method was developed to measure contents of 12 components of You-Gui-Wan in rat plasma. Considering that pathological changes might directly affect the pharmacokinetic behavior of drugs, this method was further applied to compare pharmacokinetics between normal and osteoporotic animals. The results indicated that osteoporosis significantly altered the pharmacokinetic characteristics of the 12 components. Thus, the pharmacokinetics of You-Gui-Wan evaluated under osteoporotic conditions was much closer to clinical practice than that in normal physiological states. Thus, the optimized analytical method, along with the pharmacokinetic evaluation in the osteoporotic model may offer a more comprehensive understanding to elucidate the anti-osteoporosis mechanism of You-Gui-Wan. These findings may aid in developing a more effective treatment plan for osteoporosis.

Prognostic nutritional index, a novel biomarker which predicts worse prognosis in diffuse large B cell lymphoma.

The prognostic nutritional index (PNI), an indicator of nutritional status and systemic inflammation, is associated with survival in several types of lymphoma. The purpose of this study was to investigate the prognostic value of PNI in diffuse large B cell lymphoma (DLBCL). With three hundred and ten patients were enrolled, the median level of PNI was 45.90 (range 25.30-139.70). According to the receiver operating characteristic (ROC) curve, 44.85 was determined to be the best cutoff value to divide patients into two different groups. With a median follow-up of 33.3 months (range 3.5-118.5), compared with the high PNI group, the 3-year and adjusted 3-year progression-free survival (PFS) and overall survival (OS) were worse in the low PNI group (all P < 0.050). Multivariate Cox analysis suggested that low PNI was an independent risk factor for PFS (hazard ratio (HR) 2.196, 95 % CI 1.197-4.030, P = 0.011) and showed a tendency to predict inferior OS (HR 1.918, 95 % CI 0.932-3.948, P = 0.077). Furthermore, PNI combined with other significant prognostic factors to build a novel prognostic index, namely NPI, was more accurate than the National Comprehensive Cancer Network international prognostic index (NCCN-IPI) to predict worse PFS and had a similar effect on predicting OS. All these findings suggested that PNI, as a novel available biomarker, was of prognostic significance in DLBCL patients.

An LC-MS/MS method for simultaneous quantification of 11 components of Xian-Xiong-Gu-Kang in the plasma of osteoarthritic rats and pharmacokinetic analysis.

Xian-Xiong-Gu-Kang is composed of Epimedium brevicornu, Ligusticum chuanxiong, Radix clematidis, Cinnamomum cassia, and Fructus xanthii. It is used to treat numbness and pain of limbs. In this study, we developed a method to simultaneously quantify 11 components of Xian-Xiong-Gu-Kang (icarrin, epimedin A, epimedin B, epimedin C, icariside II, chlorogenic acid, ligustilide, senkyunolide A, senkyunolide I, ferulic acid, and cinnamic acid) in rat plasma using ultra-performance liquid chromatography coupled with quadrupole linear ion trap mass spectrometry. Chromatographic separation was performed on an ACQUITY UPLC BEH C18 column using gradient elution with a mobile phase comprising acetonitrile and 0.05% (v/v) formic acid aqueous solution. Mass spectrometry detection was performed using positive and negative electrospray ionization in the multiple reaction monitoring mode. The calibration curves of the 11 constituents were linear, with correlation coefficients > 0.99. The intra- and interday accuracy and precision values were within ±15.0%. The extraction recoveries of the 11 constituents and two internal standards were between 66.05 and 105.40%, and the matrix effects were between 86.74 and 112.86%. Using this method, the pharmacokinetic features of the 11 constituents were elucidated in the plasma of osteoarthritic rats after oral administration of the Xian-Xiong-Gu-Kang extract.

Mechanical Insights into Thiol-Mediated Synergetic Biotransformation of Cadmium and Selenium in Nematodes.

Cadmium ion (Cd2+) is a common environmental pollutant with high biotoxicity. Interestingly, the Cd2+ biotoxicity can be alleviated by the coexisting selenite (SeO32-), which induces the formation of cadmium selenide-rich nanoparticles (CdSe NPs) under the function of thiol-capping peptides. However, the detailed biochemical mechanisms by which Cd and Se are synergistically transformed into CdSe NPs in living organisms remain unclear so far. Here, we shed light on the molecular basis of such biotransformation processes in Caenorhabditis elegans by focusing on the roles of several key thiol-capping peptides. By monitoring the compositional and structural changes of the Cd and Se species and the genetic-level responses of nematodes, we revealed the specific roles of glutathione (GSH) and phytochelatins (PCs) in mediating the CdSe NP formation. With the aid of in vitro bioassembly assay and density functional theory calculations, the detailed Cd-Se interaction pathways were further deciphered: the ingested Cd binds predominantly to GSH and PCs in sequence, then further interacts with selenocysteine to form tetrahedral-structured PC2-Cd2-Sec2 complex, and ultimately grows into CdSe NPs. This work provides molecular-level insights into the Cd-Se interaction in C. elegans and lays a basis for controlling the ecological and health risks of heavy metals in polluted environment.

Non-invasive physical therapy as salvage measure for ischemic skin flap: A literature review.

This review focuses on the available evidence regarding the molecular mechanisms and treatment potential of several non-surgical physical therapies for managing flap ischemia to propose a non-invasive, economical, and simple treatment to improve flap survival. A review of the literature was conducted on the topics of various non-invasive methods for the treatment of ischemic necrosis of the distal end of the flap between 1988 and 2019. A total of 52 published studies were reviewed on the applications of hyperbaric oxygen therapy, electrical stimulation therapy, heat stress pretreatment, phototherapy, and vibration therapy to manage skin flap necrosis. The underlying molecular mechanisms of these physical therapies on revitalizing the dying skin flaps were discussed and preliminary clinical uses of these therapies to salvage the necrotic skin flaps were pooled and summarized for clarifying the safety and feasibility of these methods. Various physical therapy regimens have been ushered to manage necrotic development in cutaneous flaps. With the refinement of these new technologies and enhancement of related basic science research on vascular revitalization, the prevention and treatment of flap ischemia will enter a new era.

Identification and Functional Characterization of Metabolites for Bone Mass in Peri- and Postmenopausal Chinese Women.

CONTEXT: Although metabolic profiles appear to play an important role in menopausal bone loss, the functional mechanisms by which metabolites influence bone mineral density (BMD) during menopause are largely unknown. OBJECTIVE: We aimed to systematically identify metabolites associated with BMD variation and their potential functional mechanisms in peri- and postmenopausal women. DESIGN AND METHODS: We performed serum metabolomic profiling and whole-genome sequencing for 517 perimenopausal (16%) and early postmenopausal (84%) women aged 41 to 64 years in this cross-sectional study. Partial least squares regression and general linear regression analysis were applied to identify BMD-associated metabolites, and weighted gene co-expression network analysis was performed to construct co-functional metabolite modules. Furthermore, we performed Mendelian randomization analysis to identify causal relationships between BMD-associated metabolites and BMD variation. Finally, we explored the effects of a novel prominent BMD-associated metabolite on bone metabolism through both in vivo/in vitro experiments. RESULTS: Twenty metabolites and a co-functional metabolite module (consisting of fatty acids) were significantly associated with BMD variation. We found dodecanoic acid (DA), within the identified module causally decreased total hip BMD. Subsequently, the in vivo experiments might support that dietary supplementation with DA could promote bone loss, as well as increase the osteoblast and osteoclast numbers in normal/ovariectomized mice. Dodecanoic acid treatment differentially promoted osteoblast and osteoclast differentiation, especially for osteoclast differentiation at higher concentrations in vitro (eg,10, 100 µM). CONCLUSIONS: This study sheds light on metabolomic profiles associated with postmenopausal osteoporosis risk, highlighting the potential importance of fatty acids, as exemplified by DA, in regulating BMD.

Ginger-partitioned moxibustion plus pediatric massage for treating infantile diarrhea due to spleen deficiency: a randomized controlled clinical trial / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of ginger-partitioned moxibustion plus pediatric massage (tuina) in treating infantile diarrhea due to spleen deficiency. Methods: Ninety infants were randomly divided into a massage plus moxibustion group, a massage group and a drug group by the random number table method, with 30 cases in each group. The intervention was conducted for two consecutive courses. The infants in the massage plus moxibustion group were treated with pediatric massage and ginger-partitioned moxibustion at Shenque (CV 8). The infants in the massage group were treated with pediatric massage alone, while those in the drug group were treated with smecta. The primary and secondary symptom scales were assessed before and after treatment and at the follow-ups, and the total effective rate was evaluated after treatment. Results: The total effective rate in the massage plus moxibustion group was significantly different from that in the massage group and drug group (both P<0.05). After treatment, the scores of primary and secondary symptoms decreased in all three groups, with statistically significant intra-group differences (all P<0.05); the scores of primary symptoms were significantly different between the massage plus moxibustion group and the drug group (P<0.05); the scores of secondary symptoms in the massage plus moxibustion group and the massage group were significantly different from that in the drug group (both P<0.05). The differences in the time to recover normal bowel movement frequency among the three groups were not statistically significant (P>0.05). Conclusion: Ginger-partitioned moxibustion plus pediatric massage compared with pediatric massage or smecta monotherapy shows superior clinical efficacy in treating infantile diarrhea due to spleen deficiency, and has the advantages of appetite improvement, physique strengthening and short course.

[Preparation of curcumin TPP-PEG-PE nanomicelles with mitochondrial targeting and lysosomal escape functions and its effect on promoting breast cancer cell apoptosis].

Orthogonal experiments were used to optimize the process parameters of curcumin TPP-PEG-PCL nanomicelles; the particle size, electric potential and morphology under the electron microscope were systematically detected for the curcumin TPP-PEG-PCL nanomicelles; and the stability and in vitro release of the curcumin TPP-PEG-PCL nanomicelles were investigated. With DID fluorescent dye as the fluorescent probe, flow cytometry was used to study the uptake of nanomicelles by breast cancer cells, and laser confocal microscopy was used to study the mitochondrial targeting and lysosomal escape functions of nanomicelles. Under the same dosage conditions, the effect of curcumin TPP-PEG-PCL nanomicelles on promoting the apoptosis of breast cancer cells was evaluated. The optimal particle size of curcumin TPP-PEG-PCL nanomicelle was(17.3±0.3) nm, and the Zeta potential was(14.6±2.6) mV in orthogonal test. Under such conditions, the micelle appeared as regular spheres under the transmission electron microscope. Fluorescence test results showed that TPP-PEG-PCL nanomicelles can promote drug uptake by tumor cells, escape from lysosomal phagocytosis, and target the mitochondria. The cell survival rate and Hoechst staining positive test results showed that curcumin TPP-PEG-PCL nanomicelles had a good effect on promoting apoptosis of breast cancer cells. The curcumin TPP-PEG-PCL micelles can significantly reduce the mitochondrial membrane potential of breast cancer cells, increase the release of cytochrome C, significantly increase the expression of pro-apoptotic protein Bcl-2 and reduce the expression of anti-apoptotic Bax protein. These test results were significantly better than those of curcumin PEG-PCL nanomicelles and curcumin, with statistically significant differences. The results revealed that curcumin TPP-PEG-PCL nanomicelles can well target breast cancer cell mitochondria and escape from the lysosomal capture, thereby enhancing the drug's role in promoting tumor cell apoptosis.

Antibody response and therapy in COVID-19 patients: what can be learned for vaccine development?

The newly emerged severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has infected millions of people and caused tremendous morbidity and mortality worldwide. Effective treatment for coronavirus disease 2019 (COVID-19) due to SARS-CoV-2 infection is lacking, and different therapeutic strategies are under testing. Host humoral and cellular immunity to SARS-CoV-2 infection is a critical determinant for patients' outcomes. SARS-CoV-2 infection results in seroconversion and production of anti-SARS-CoV-2 antibodies. The antibodies may suppress viral replication through neutralization but might also participate in COVID-19 pathogenesis through a process termed antibody-dependent enhancement. Rapid progress has been made in the research of antibody response and therapy in COVID-19 patients, including characterization of the clinical features of antibody responses in different populations infected by SARS-CoV-2, treatment of COVID-19 patients with convalescent plasma and intravenous immunoglobin products, isolation and characterization of a large panel of monoclonal neutralizing antibodies and early clinical testing, as well as clinical results from several COVID-19 vaccine candidates. In this review, we summarize the recent progress and discuss the implications of these findings in vaccine development.

Functional interactions between complex I and complex II with nNOS in regulating cardiac mitochondrial activity in sham and hypertensive rat hearts.

Nitric oxide (NO) affects mitochondrial activity through its interactions with complexes. Here, we investigated regulations of complex I (C-I) and complex II (C-II) by neuronal NO synthase (nNOS) in the presence of fatty acid supplementation and the impact on left ventricular (LV) mitochondrial activity from sham and angiotensin II (Ang-II)-induced hypertensive (HTN) rats. Our results showed that nNOS protein was expressed in sham and HTN LV mitochondrial enriched fraction. In sham, oxygen consumption rate (OCR) and intracellular ATP were increased by palmitic acid (PA) or palmitoyl-carnitine (PC). nNOS inhibitor, S-methyl-l-thiocitrulline (SMTC), did not affect OCR or cellular ATP increment by PA or PC. However, SMTC increased OCR with PA + malonate (a C-II inhibitor), but not with PA + rotenone (a C-I inhibitor), indicating that nNOS attenuates C-I with fatty acid supplementation. Indeed, SMTC increased C-I activity but not that of C-II. Conversely, nNOS-derived NO was increased by rotenone + PA in LV myocytes. In HTN, PC increased the activity of C-I but reduced that of C-II, consequently OCR was reduced. SMTC increased both C-I and C-II activities with PC, resulted in OCR enhancement in the mitochondria. Notably, SMTC increased OCR only with rotenone, suggesting that nNOS modulates C-II-mediated OCR in HTN. nNOS-derived NO was partially reduced by malonate + PA. Taken together, nNOS attenuates C-I-mediated mitochondrial OCR in the presence of fatty acid in sham and C-I modulates nNOS activity. In HTN, nNOS attenuates C-I and C-II activities whereas interactions between nNOS and C-II maintain mitochondrial activity.

[Research progress on hepatotoxicity of traditional Chinese medicine based on metabonomics].

With the continuous development of Chinese medicine, traditional Chinese medicine(TCM) has been widely used in the treatment of diseases and health care. At the same time, the toxic and side effects of TCM have been gradually concerned. The liver, as an important place for drug metabolism, is a major target organ for drug toxicity. Clinical reports on liver injury caused by TCM are common, and the problem of liver toxicity of TCM has become an important reason to limit the internationalization of TCM. Metabono-mics is a newly booming subject to study the metabolic pathway of biological system. It shows integrity and systematicness in the study of hepatotoxicity of TCM, which provides a new technical method for finding the early biomarkers of liver injury of TCM and exploring the mechanism of hepatotoxicity of TCM. In this paper, the methods of metabonomics in the study of hepatotoxicity of TCM, as well as the research progress of hepatotoxicity monomer, extract and attenuation of hepatotoxic TCM based on metabonomics were reviewed in order to provide reference for the further study of hepatotoxicity of TCM.

Anti-Inflammatory and Antibacterial Activity Constituents from the Stem of Cinnamomum validinerve.

One new dibenzocycloheptene, validinol (1), and one butanolide firstly isolated from the natural source, validinolide (2), together with 17 known compounds were isolated from the stem of Cinnamomum validinerve. Among the isolates, lincomolide A (3), secosubamolide (7), and cinnamtannin B1 (19) exhibited potent inhibition on both superoxide anion generation (IC50 values of 2.98 ± 0.3 µM, 4.37 ± 0.38 µM, and 2.20 ± 0.3 µM, respectively) and elastase release (IC50 values of 3.96 ± 0.31 µM, 3.04 ± 0.23 µM, and 4.64 ± 0.71 µM, respectively) by human neutrophils. In addition, isophilippinolide A (6), secosubamolide (7), and cinnamtannin B1 (19) showed bacteriostatic effects against Propionibacterium acnes in in vitro study, with minimal inhibitory concentration (MIC) values at 16 µg/mL, 16 µg/mL, and 500 µg/mL, respectively. Further investigations using the in vivo ear P. acnes infection model showed that the intraperitoneal administration of the major component cinnamtannin B1 (19) reduced immune cell infiltration and pro-inflammatory cytokines TNF-α and IL-6 at the infection sites. The results demonstrated the potential of cinnamtannin B1 (19) for acne therapy. In summary, these results demonstrated the anti-inflammatory potentials of Formosan C. validinerve during bacterial infections.

Cardiac complex II activity is enhanced by fat and mediates greater mitochondrial oxygen consumption following hypoxic re-oxygenation.

Recent evidence suggests that mitochondrial complex II is an essential mediator of myocardial ischemia-reperfusion injury. The present study aimed to investigate the effects of fatty acid supplementation or high-fat diet (HFD) on cardiac mitochondrial activity. The changes of complex I and complex II activities and mitochondrial oxygen consumption rate (OCR) following hypoxia and re-oxygenation under these conditions were studied. Our results have shown that OCR (mitochondrial activity) was significantly increased with palmitoylcarnitine supplementation in mitochondria-enriched fraction from C57BL/6 mice hearts. Mitochondrial complex I activity was unaffected by palmitoylcarnitine but complex II activity was enhanced. Re-oxygenation following 30-min hypoxia transiently increased OCR but such an effect on OCR was abolished by complex II inhibitor, malonate, but not by complex I inhibitor, rotenone, despite that complex I activity was significantly increased with re-oxygenation following hypoxia in the presence of palmitoylcarnitine. Furthermore, OCR and complex II activity were significantly increased in the mitochondria from high-fat diet mice heart compared with those of normal or low-fat diet mice. Re-oxygenation to mitochondria following 30-min hypoxia increased OCR in all three groups but significantly more in HFD. Malonate abolished re-oxygenation-induced OCR increment in all groups. Our results indicate that complex II activity and OCR are enhanced with palmitoylcarnitine or in HFD mice heart. Although re-oxygenation following hypoxia enhanced complex II and complex I activities, complex II plays an important role in increasing mitochondrial activity, which may be instrumental in myocardial injury following ischemic reperfusion.

Da-Cheng-Qi Decoction () Combined with Lactobacillus Acidophilus Improves Gastrointestinal Function of Traumatic Brain-Injured Model Mice.

OBJECTIVE: To investigate the effects of Da-Cheng-Qi Decoction (DCQD, ) combined with Lactobacillus acidophilus (LA) on the recovery of gastrointestinal (GI) function in traumatic brain-injured (TBI) mice. METHODS: A total of 150 male C57BL/6 mice were randomly divided into sham-injury, normal saline (NS), DCQD (0.4 mL/day), LA (⩾1 × 1010 cfu/day LA), DCQD+LA (LA administration at the same dosage after 4 h of feeding DCQD), and ½ DCQD+LA groups (LA administration at the same dosage after 4 h of feeding ½ DCQD dose) by a random number table, 5-8 mice in each group. The sever TBI model was constructed according to Feeney's enhanced gravitational forces of free falling. On days 1, 3, and 7 post-TBI, plasma diamine oxidase (DAO) and D-lactic acid levels were assessed by enzyme-linked immunosorbent assay (ELISA). Occludin expression in the intestinal epithelium was assessed by Western blot analysis. Transmission electron microscopy (TEM) was used to observe the morphological changes in the network structure of interstitial cells of Cajal (ICC) and change of enteric nervous system-ICC-smooth muscle cell (ENS-ICC-SMC). Immunofluorescence staining was used to detect changes in the network structure of the ICC. RESULTS: Compared with the NS group, occludin expression in the DCQD+LA group significantly increased on Day 1, 3, and 7 post-TBI (P<0.05 or P<0.01). The concentration of DAO significantly decreased in the LA, DCQD, and DCQD+LA groups on Day 3 and 7, whilst the D-lactate concentrations in the LA and ½ DCQD+LA groups decreased on Day 1 and 3 post-injury (P<0.05 or P<0.01). The NS group experienced a great damage on the ENS-ICC-SMC network morphology and ICC network structure, and all treatment groups had some improvements, among which the DCQD+LA group presented relatively intact network morphology. CONCLUSIONS: DCQD combined with LA treatment could effectively repair the intestinal mucosal barrier and improve GI motility in mice after TBI. The combination of DCQD and LA was more effective than their respective monotherapies.