Structural characterization and therapeutic effect of Alhagi honey oligosaccharide on liver fibrosis in mice.

Alhagi honey is derived from the secretory granules of Alhagi pseudoalhagi Desv., a leguminous plant commonly known as camelthorn. Modern medical research has demonstrated that the extract of Alhagi honey possesses regulatory properties for the gastrointestinal tract and immune system, as well as exerts anti-tumor, anti-oxidative, anti-inflammatory, anti-bacterial, and hepatoprotective effects. The aim of this study was to isolate and purify oligosaccharide monomers (referred to as Mel) from camelthorn and elucidate their structural characteristics. Subsequently, the impact of Mel on liver injury induced by carbon tetrachloride (CCl4) in mice was investigated. The analysis identified the isolated oligosaccharide monomer (α-D-Glcp-(1 â†’ 3)-ß-D-Fruf-(2 â†’ 1)-α-D-Glcp), with the molecular formula C18H32O16. In a mouse model of CCl4-induced liver fibrosis, Mel demonstrated significant therapeutic effects by attenuating the development of fibrosis. Moreover, it enhanced anti-oxidant enzyme activity (glutathione peroxidase and superoxide dismutase) in liver tissues, thereby reducing oxidative stress markers (malondialdehyde and reactive oxygen species). Mel also improved serum albumin levels, lowered liver enzyme activities (aspartate aminotransferase and alanine aminotransferase), and decreased inflammatory factors (tumor necrosis factor-alpha, interleukin-1 beta, and interleukin-6). Immunohistochemistry, immunofluorescence, and western blotting analyses confirmed the ability of Mel to downregulate hepatic stellate cell-specific markers (collagen type I alpha 1 chain, alpha-smooth muscle actin, transforming growth factor-beta 1. Non-targeted metabolomics analysis revealed the influence of Mel on metabolic pathways related to glutathione, niacin, pyrimidine, butyric acid, and amino acids. In conclusion, the results of our study highlight the promising potential of Mel, derived from Alhagi honey, as a viable candidate drug for treating liver fibrosis. This discovery offers a potentially advantageous option for individuals seeking natural and effective means to promote liver health.

Evaluation of the mechanism of Gong Ying San activity on dairy cows mastitis by network pharmacology and metabolomics analysis.

OBJECTIVES: The goal of this investigation was to identify the main compounds and the pharmacological mechanism of the traditional Chinese medicine formulation, Gong Ying San (GYS), by infrared spectral absorption characteristics, metabolomics, network pharmacology, and molecular-docking analysis for mastitis. The antibacterial and antioxidant activities were determined in vitro. METHODS: The chemical constituents of GYS were detected by ultra-high-performance liquid chromatography Q-extractive mass spectrometry (UHPLC-QE-MS). Related compounds were screened from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP, http://tcmspw.com/tcmsp.php) and the Encyclopedia of Traditional Chinese Medicine (ETCM, http://www.tcmip.cn/ETCM/index.php/Home/) databases; genes associated with mastitis were identified in DisGENT. A protein-protein interaction (PPI) network was generated using STRING. Gene ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment screening was conducted using the R module. Molecular-docking analyses were performed with the AutoDockTools V1.5.6. RESULTS: Fifty-four possible compounds in GYS with forty likely targets were found. The compound-target-network analysis showed that five of the ingredients, quercetin, luteolin, kaempferol, beta-sitosterol, and stigmasterol, had degree values >41.6, and the genes TNF, IL-6, IL-1ß, ICAM1, CXCL8, CRP, IFNG, TP53, IL-2, and TGFB1 were core targets in the network. Enrichment analysis revealed that pathways associated with cancer, lipids, atherosclerosis, and PI3K-Akt signaling pathways may be critical in the pharmacology network. Molecular-docking data supported the hypothesis that quercetin and luteolin interacted well with TNF-α and IL-6. CONCLUSIONS: An integrative investigation based on a bioinformatics-network topology provided new insights into the synergistic, multicomponent mechanisms of GYS's anti-inflammatory, antibacterial, and antioxidant activities. It revealed novel possibilities for developing new combination medications for reducing mastitis and its complications.

Study on the potential mechanism of Qingxin Lianzi Yin Decoction on renoprotection in db/db mice via network pharmacology and metabolomics.

BACKGROUND: Diabetic nephropathy (DN) was one of the most popular and most significant microvascular complications of diabetes mellitus. Qingxin Lianzi Yin Decoction (QXLZY) was a traditional Chinese classical formula, suitable for chronic urinary system diseases. QXLZY had good clinical efficacy in early DN, but the underlying molecular mechanism remained unrevealed. PURPOSE: This study aimed to establish the content determination method of QXLZY index components and explore the mechanism of QXLZY on DN by network pharmacology and metabolomics studies. METHODS: Firstly, the content determination methods of QXLZY were established with calycosin-7-O-ß-d-glucoside, acteoside, baicalin and glycyrrhizic acid as index components. Secondly, pharmacological experiments of QXLZY were evaluated using db/db mice. UHPLC-LTQ-Orbitrap MS was used to carry out untargeted urine metabolomics, serum metabolomics, and kidney metabolomics studies. Thirdly, employing network pharmacology, key components and targets were analyzed. Finally, targeted metabolomics studies were performed on the endogenous constituents in biological samples for validation based on untargeted metabolomics results. RESULTS: A method for the simultaneous determination of multiple index components in QXLZY was established, which passed the comprehensive methodological verification. It was simple, feasible, and scientific. The QXLZY treatment alleviated kidney injury of db/db mice, included the degree of histopathological damage and the level of urinary microalbumin/creatinine ratio. Untargeted metabolomics studies had identified metabolic dysfunction in pathways associated with amino acid metabolism in db/db mice. Treatment with QXLZY could reverse metabolite abnormalities and influence the pathways related to energy metabolism and amino acid metabolism. It had been found that pathways with a high degree were involved in signal transduction, prominently on amino acids metabolism and lipid metabolism, analyzed by network pharmacology. Disorders of amino acid metabolism did occur in db/db mice. QXLZY could revert the levels of metabolites, such as quinolinic acid, arginine, and asparagine. CONCLUSION: This study was the first time to demonstrate that QXLZY alleviated diabetes-induced pathological changes in the kidneys of db/db mice by correcting disturbances in amino acid metabolism. This work could provide a new experimental basis and theoretical guidance for the rational application of QXLZY on DN, exploring the new pharmacological effect of traditional Chinese medicine, and promoting in-depth research and development.

Feasibility of implementing acupuncture in medically underserved breast cancer survivors (FAB): A protocol.

Nearly 94% of breast cancer survivors experience one or more symptoms or side effects during or after endocrine therapy. Joint pain, hot flashes, sleep disturbance, fatigue, depression, and anxiety are the most common concurrent symptoms, some of which can persist for 5 to 10 years. Acupuncture is a holistic modality that addresses multiple symptoms and side effects in a single therapy. Acupuncture has not yet been investigated for its effectiveness in treating the multiple symptoms experienced by breast cancer survivors receiving endocrine therapy. Medically underserved breast cancer survivors typically have limited access to acupuncture. The barriers limiting access to acupuncture need to be removed to enable equal access to breast cancer survivors for this evidence-based treatment. Thus, we developed a randomized controlled trial with a 5-week acupuncture intervention versus usual care for medically underserved breast cancer survivors. Mixed methods (semi-structured interviews, surveys, study notes) will be used to obtain in-depth understanding of barriers and facilitators for eventual implementation of the acupuncture intervention. This study will facilitate the widespread implementation, dissemination, and sustained utilization of acupuncture for symptom management among medically underserved breast cancer survivors receiving endocrine therapy.

Photoactivatable Immunostimulatory Nanomedicine for Immunometabolic Cancer Therapy.

A rationally designed immunostimulant (CC@SiO2-PLG) with a photoactivatable immunotherapeutic function for synergetic tumor therapy is reported. This CC@SiO2-PLG nanoplatform comprises catalase and a photosensitizer (Ce6) co-encapsulated in a silica capsule, to which an immunostimulant is conjugated through a reactive oxygen species-cleavable linker. After accumulating in tumor tissue, CC@SiO2-PLG generates O2 to relieve tumor hypoxia and promotes the production of singlet oxygen (1O2) upon laser irradiation, resulting in not only tumor destruction but also the release of tumor-associated antigens (TAAs). Simultaneously, the linker breakage by the photoproduced 1O2 leads to the remote-controlled release of conjugated indoleamine 2,3-dioxygenase (IDO) inhibitor from CC@SiO2-PLG and consequent immunosuppressive tumor microenvironment reversion. The released TAAs in conjunction with the inhibition of the IDO-mediated tryptophan/kynurenine metabolic pathway induced a boosted antitumor immune response to the CC@SiO2-PLG-mediated phototherapy. Therefore, the growth of primary/distant tumors and lung metastases in a mouse xenograft model was greatly inhibited, which was not achievable by phototherapy alone.

Virtual screening based on pharmacophore model for developing novel HPPD inhibitors.

4-Hydroxyphenylpyruvate dioxygenase (HPPD) is an important target for herbicide design. A multilayered virtual screening workflow was constructed by combining two pharmacophore models based on ligand and crystal complexes, molecular docking, molecular dynamics (MD), and biological activity determination to identify novel small-molecule inhibitors of HPPD. About 110, 000 compounds of Bailingwei and traditional Chinese medicine databases were screened. Of these, 333 were analyzed through docking experiments. Five compounds were selected by analyzing the binding pattern of inhibitors with amino acid residues in the active pocket. All five compounds could produce stable coordination with cobalt ion, and form favorable π-π interactions. MD simulation demonstrated that Phe381 and Phe424 made large contributions to the strength of binding. The enzyme activity experiment verified that compound-139 displayed excellent potency against AtHPPD (IC50 = 0.742 µM), however, compound-5222 had inhibitory effect on human HPPD (IC50 = 6 nM). Compound-139 exhibited herbicidal activity to some extent on different gramineous weeds. This work provided a strong insight into the design and development of novel HPPD inhibitor using in silico techniques.

[Analysis on disease burden and direct medical cost of Xueshuan Xinmaining Tablets in patients with cerebral infarction and coronary heart disease].

The increasing burden of cardiovascular disease in China has become a major public health problem, and the prevention and treatment of cardiovascular disease is in urgent need. For the reality of integrated Chinese and Western medicine in the Chinese health care system, we can consider the service ability of traditional Chinese medicine. Xueshuan Xinmaining Tablet is a kind of Chinese patent medicine commonly used in the treatment of recovery stage of ischemic stroke and angina pectoris of coronary heart disease. Based on the data of hospitalized patients covered by national urban basic medical insurance of China Medical Insurance Research Association in 2013, this study evaluated the treatment cost and detailed composition of the cost for the patients with cerebral infarction and coronary heart disease treated by Xueshuan Xinmaining Tablets. At the same time, the differences in disease burden and direct medical expenses among Xueshuan Xinmaining Tablets group, Western medicine group and another commonly used Chinese patent medicine group were analyzed. Among the three groups of patients with cerebral infarction and coronary heart disease, the hospitalization rates caused by various causes(44.4% and 29.6%) and diseases(20.8% and 5.2%) in Xueshuan Xinmaining Tablets group were the lowest(all P<0.01), and the number of hospitalization times in half a year was highest in the common Chinese patent medicine group(all P<0.01). In patients with cerebral infarction, the median annual total outpatient expenses were 7 476.8, 7 601.8, 15 650.1 yuan respectively in Western medicine group, Xueshuan Xinmaining Tablets group and the common Chinese patent medicine group(P<0.01), and the median hospitalization expenses were 11 620.2, 14 988.9, 13 325.6 yuan respectively(P=0.058). In patients with coronary heart disease, the total outpatient expenses of the three groups were 6 831.4, 10 228.6, 13 132.4 yuan respectively(P<0.01), and the total hospitalization expenses were 13 354.7, 14 911.5, 15 725.3 yuan respectively(P=0.134). The results showed that in patients with cerebral infarction and coronary heart disease, the hospitalization rate was lowest in Xueshuan Xinmaining Tablets group, beneficial to the turnover of hospital beds and full use of hospital medical resources. The total annual outpatient cost of Xueshuan Xinmaining Tablets group was lower than that of common Chinese patent medicine group, beneficial to reduce the burden of disease.

A Chromosome-Level Genome Assembly of Garlic (Allium sativum) Provides Insights into Genome Evolution and Allicin Biosynthesis.

Garlic, an economically important vegetable, spice, and medicinal crop, produces highly enlarged bulbs and unique organosulfur compounds. Here, we report a chromosome-level genome assembly for garlic, with a total size of approximately 16.24 Gb, as well as the annotation of 57 561 predicted protein-coding genes, making garlic the first Allium species with a sequenced genome. Analysis of this garlic genome assembly reveals a recent burst of transposable elements, explaining the substantial expansion of the garlic genome. We examined the evolution of certain genes associated with the biosynthesis of allicin and inulin neoseries-type fructans, and provided new insights into the biosynthesis of these two compounds. Furthermore, a large-scale transcriptome was produced to characterize the expression patterns of garlic genes in different tissues and at various growth stages of enlarged bulbs. The reference genome and large-scale transcriptome data generated in this study provide valuable new resources for research on garlic biology and breeding.

Intravitreal Conbercept Injection as an Adjuvant in Vitrectomy with Silicone Oil Infusion for Severe Proliferative Diabetic Retinopathy.

Purpose: To assess the clinical effects of preoperative, intraoperative, or preoperative combined with intraoperative intravitreal conbercept (IVC) injection in vitrectomy with silicone oil tamponade for severe proliferative diabetic retinopathy (PDR). Methods: Ninety-eight eyes of 98 severe PDR patients undergoing vitrectomy with silicone oil tamponade were randomly assigned to 3 groups: Group 1 (34 eyes) received IVC injections 3 to 5 days before surgery; Group 2 (35 eyes) received IVC injections at the end of surgery; and Group 3 (29 eyes) received IVC injections 3 to 5 days before and at the end of operation. Follow-up examinations were performed for 6 months. Results: The incidence and severity of intraoperative bleeding were not significantly different (P = 0.233). However, the duration of surgery was significantly shorter in Group 1 and Group 3 compared with Group 2 (P < 0.001). The incidences of early and late recurrent vitreous hemorrhage (VH) were 32.35%, 28.57%, and 13.80%, respectively. At 6-month follow-up, mean best-corrected visual acuity had significantly increased to 1.25 ± 0.45 logMAR in Group 1, 1.29 ± 0.46 logMAR in Group 2, 1.16 ± 0.44 logMAR in Group 3 (all P < 0.001). The incidence of postoperative VH, neovascular glaucoma, and retinal detachment in Group 3 was slightly lower, however, no significant differences were observed (all P > 0.05). In young patients, similar results were observed and Group 3 had better visual improvements (P = 0.037). Conclusions: Preoperative IVC injection could be a safe and effective adjunct in pars plana vitrectomy with silicone oil tamponade for severe PDR. Preoperative combined with intraoperative IVC are promising, especially in young patients.

Dietary oils modify lipid molecules and nutritional value of fillet in Nile tilapia: A deep lipidomics analysis.

The nutritional value of fish fillet can be largely affected by dietary oils. However, little is known about how dietary oils modify lipid molecules in fish fillets. Through biochemical and lipidomics assays, this study demonstrated the molecular characteristics of fillet lipids in Nile tilapia fed with different oils for six weeks. High 18:2n-6 and low 18:3n-3 deposition in phosphoglycerides resulted high 18:2n-6/18:3n-3 ratio in tilapia. Dietary n-3 VLCUFAs intake increased its deposition at sn-1/3 of triglycerides and at sn-2 of phosphatidylcholines. Irrespective of dietary oil, 16:0 was distributed preferentially at the outer positions of glycerol backbone. High 18:2n-6 accumulated at sn-2 position for fish fed with n-3 PUFA-enriched oils. High 18:3n-3 deposited at sn-1/3 in TG, sn-1 in phosphatidylethanolamines, while at sn-2 in phosphatidylcholines. Together, dietary oils change the composition and positional distribution of fatty acids on the glycerol backbone, and change nutritional value of fish for human health.

Total sesquiterpene lactones isolated from Inula helenium L. attenuates 2,4-dinitrochlorobenzene-induced atopic dermatitis-like skin lesions in mice.

BACKGROUND: Inula helenium L. is an herb whose anti-inflammatory properties are attributed to its active components, the sesquiterpene lactones (SLs). Our previous study demonstrated that the total sesquiterpene lactones isolated from Inula helenium L. (TSL-IHL), consisting mainly of alantolactone (AL) and isoalantolactone (IAL), may have potential in the prevention and treatment of rheumatoid arthritis (RA). However, the effect of TSL-IHL on atopic dermatitis (AD) has not been studied yet. AIM OF THE STUDY: The present study evaluates the potential of TSL-IHL as a treatment for AD. METHODS/STUDY DESIGNS: The effects of TSL-IHL on the expression of inflammatory genes and the activation of NF-κB signaling pathway in HaCat cells were examined by quantitative real-time PCR and western blotting, respectively, and compared with those of AL and IAL. The protective effect of TSL-IHL against AD was tested in a mouse model induced by 2,4-dinitrochlorobenzene (DNCB), in which AD-like skin lesions were induced in ICR mice by sensitizing once with 100 µl of 7% DNCB painted on their shaved back skin and then challenging with 20 µl of 0.2% DNCB five times on their right ears at 3 day intervals starting on day 5 post-sensitization. RESULTS: TSL-IHL, as well as AL and IAL, could all inhibit TNF-α-induced activation of NF-κB and the expression of TNF-α, IL-1, and IL-4 in HaCat cells in a dose-dependent manner in the range of 0.6-2.4 µg/ml. The topical application of TSL-IHL (1% W/W in emollient cream) attenuated DNCB-induced dermatitis severity and right ear swelling. The serum levels of IgE, TNF-α and IFN-γ in TSL-IHL-treated mice were reduced by 81.39%, 89.69%, and 87.85%, respectively, while the mRNA levels of IL-4, IL-5 and IL-13, in the back-skin lesions of TSL-IHL-treated mice were reduced by 39.21%, 40.62% and 48.12%, respectively, compared with the untreated controls. Histopathological examination showed that TSL-IHL treatment reduced epidermis/dermis thickening and dermal inflammatory infiltration in both ear and back skins. CONCLUSIONS: We suggest that TSL-IHL inhibited the development of AD-like skin symptoms by regulating cytokine expression and may be an effective alternative therapy for AD.

Use of antimicrobial peptides as a feed additive for juvenile goats.

Although antimicrobial peptides (AMPs) have been used as feed additives, only a few studies have examined their use in ruminants. In this study, we evaluated the use of AMPs(recombinant swine defensin and a fly antibacterial peptide were mixed by 1:1) as a medicated feed additive for juvenile goats. Dietary treatments included control groups (group I: 300 g concentrate; group III: 600 g concentrate), and AMP-supplemented groups (group II: 300 g concentrate + 3.0 g AMPs; group IV: 600 g concentrate + 3.0 g AMPs). AMP-treated groups exhibited an increase in bacterial genera, including Fibrobacter, Anaerovibrio, and Succiniclasticum, and the ciliate genus Ophryoscolex; as well a reduction in bacterial genera, such as Selenomonas, Succinivibrio, and Treponema, and the ciliate genera Polyplastron, Entodinium, and Isotricha. The changes in Fibrobacter, Anaerovibrio, Ophryoscolex, Polyplastron, Entodinium, and Isotricha were related to the concentrate. AMP treatment led to increased body weight, average daily weight gain, enzymatic activity (pectinase, xylanase, and lipase), especially in the normal concentrate group, and influence on ruminal fermentation function. In addition, goats treated with AMPs had higher rumen microorganism diversity indices than the control groups. Our results demonstrate that AMPs can be utilized as feed additives for juvenile goats.

The role of miR-122-5p in negatively regulating T-box brain 1 expression on the differentiation of mouse bone mesenchymal stem cells.

To achieve neuronal differentiation of mouse bone mesenchymal stem cells (bMSCs) into neuron-like cells and explore the role of miR-122-5p that may regulate T-box brain 1 (Tbr1) expression during the induction. BMSCs were cultured and induced with butylated hydroxyanisole, retinoic acid (RA), basic fibroblast growth factor, and nerve growth factor in vitro. The cells were stained for neuron-specific enolase (NSE) and ß-III-tubulin by immunocytochemistry/immunofluorescence. MiR-122-5p that may regulate Tbr1 expression was predicted by bioinformatics and identified using a Dual-Luciferase assay. The expressions of miR-122-5p and Tbr1 were determined by real-time PCR and western blot before and after the induction. After infection of miR-122-5p, the expressions of Tbr1, NSE, and tauons were measured. BMSCs showed a short spindle shape with a uniform distribution. After 14 days, the induced cells showed neuronal traits with a pyramidal appearance. TargetScan and miRanda showed that miR-122-5p was well complementary with the target site of the Tbr1 3'-untranslated region. Identified by the Dual-Luciferase assay, we found that miR-122-5p could inhibit Tbr1 expression by binding to its 3'-untranslated region. Furthermore, the expressions of Tbr1 mRNA and protein were decreased by real-time PCR and western blot. Overexpression of miR-122-5p downregulated the expressions of Tbr1, NSE, and tauons. MiR-122-5p may negatively regulate Tbr1 expression to affect the differentiation of bMSCs into neuron-like cells.

Hypoglycemic Activity of Polysaccharides from Sweet Corncob on Streptozotocin-Induced Diabetic Rats.

A water-soluble polysaccharide (SCP-80-I) was isolated from sweet corncob using microwave-assisted compound-enzyme extraction and column chromatography. SCP-80-I is composed mainly of arabinose, mannose, glucose, and galactose in a molar ratio of 0.369:0.824:10.759:0.333, and has a molecular mass of 18350 Da and ß-glycosides linkages in its molecular structure. The preliminary hypoglycemic and hypolipidemic activity in streptozotocin-induced diabetic rats was investigated. Rats were administered daily with 100, 200, and 400 mg/kg SCP-80-I for 21 d. The SCP-80-I increased the rat body mass significantly and reduced the blood glucose level in a dose-dependent manner. The SCP-80-I reduced liver swelling; kidney and pancreas hypertrophy; and total cholesterol, triglyceride, and low-density lipoprotein-C levels significantly; and increased the level of high-density lipoproteins in streptozotocin-induced diabetic rats. These results indicate that SCP-80-I exerts a potential hypoglycemic effect in streptozotocin-induced diabetic rats.

Total sesquiterpene lactones prepared from Inula helenium L. has potentials in prevention and therapy of rheumatoid arthritis.

BACKGROUNDS: Inula helenium L. is an herb with anti-inflammatory properties. Sesquiterpene lactones (SLs), mainly alantolactone (AL) and isoalantolactone (IAL), are considered as its active ingredients. However, the anti-inflammatory effects of SL-containing extracts of I. helenium have not been explored. Here we prepared total SLs from I. helenium (TSL-IHL), analyzed its chemical constituents, and performed cellular and animal studies to evaluate its anti-inflammatory activities. MATERIALS AND METHODS: The chemical profile of TSL-IHL was analyzed by HPLC-UV. Its in vitro effects on the activation of signaling pathways and expression of inflammatory genes were examined by western blotting and quantitative real-time PCR, respectively, and compared with those of AL and IAL. Its in vivo anti-inflammatory effects were evaluated in adjuvant- and collagen-induced arthritis rat models. RESULTS: Chemical analysis showed that AL and IAL represent major constituents of TSL-IHL. TSL-IHL, as well as AL and IAL, could inhibit TNF-α-induced activation of NF-κB and MAPK pathways in b. End3 cells, suppress the expressions of MMP-3, MCP-1, and IL-1 in TNF-α-stimulated synovial fibroblasts, and IL-1, IL-6, and iNOS in LPS-activated RAW 264.7 cells in a dose-dependent manner in the range of 0.6-2.4µg/mL. Oral administration of TSL-IHL at 12.5-50mg/kg could dose-dependently alleviate the arthritic severity and paw swelling in either developing or developed phases of arthritis of rats induced by adjuvant or collagen CONCLUSIONS: These results indicated potentials of TSL-IHL in prevention and therapy of rheumatoid arthritis.

Three new sesquiterpene lactone dimers from Carpesium macrocephalum.

Three new sesquiterpene lactone dimers (SLDs), carpedilactones E-G (1-3), together with two known monomeric units, ivalin (4) and alantolactone (5), were isolated from the acetonic extract of Carpesium macrocephalum. Their chemical structures were elucidated by IR, UV, HR-ESI-MS, NMR 1D and 2D experiments, and the absolute configuration of 1-3 was resolved according to the (1)H NMR and CD spectrographic features of 1,3-/2,4-linked SLDs. Furthermore, 1 was unambiguously confirmed by Cu-Kα X-ray crystallographic analysis. Additionally, compounds 1 and 2 were revealed with potent cytotoxicities against human colon cancer HCT116 cells with IC50 values of 2.27 and 3.30 µM, respectively.

1ß-Hydroxyalantolactone, a sesquiterpene lactone from Inula japonica, attenuates atopic dermatitis-like skin lesions induced by 2,4-dinitrochlorobenzene in the mouse.

CONTEXT: 1ß-Hydroxyalantolactone (IJ-5) is a sesquiterpene lactone compound isolated from Inula japonica Thunb (Asteraceae). Sesquiterpene lactones have been shown to modulate many processes that influence inflammatory reactions. OBJECTIVE: The present study examines the protective effect of IJ-5 on atopic dermatitis (AD) in a mouse model induced by 2,4-dinitrochlorobenzene (DNCB). MATERIALS AND METHODS: AD-like skin lesions were induced in Balb/c mice by sensitizing once with painting 100 µL of 5% DNCB on their shaved back skin and then challenging with 20 µL of 0.2% DNCB five times on their right ears at 3 d interval starting on day 5 post-sensitization. IJ-5 was administrated intraperitoneally at 10 mg/kg 1 h before each DNCB challenge. RESULTS: IJ-5 treatment attenuated DNCB-induced dermatitis severity and right ear swelling. The serum levels of IgE, IL-4, and IL-6 in IJ-5-treated mice were reduced by 54.7, 56.5, and 53.0%, respectively, while the mRNA levels of TNFα, IL-1, IL-4, and IL-6 in back skin lesions of IJ-5-treated mice were reduced by 47.7, 61.5, 57.5, and 58.5%, respectively, compared with untreated controls. Histopathological examination showed that IJ-5 treatment decreased DNCB-induced hypertrophy, hyperkeratosis, and infiltration of inflammatory cells in both ear and back skins. Moreover, IJ-5 suppressed the expression of TNFα, IL-1, and IL-6 with IC50 values of 6.58, 9.48, and 7.01 µM, respectively, and inhibited the activation of NF-κB pathway in TNFα-stimulated HaCat cells. DISCUSSION AND CONCLUSION: The present study demonstrates the protective effects of IJ-5 against AD-like skin inflammation and highlights IJ-5 as a potential therapeutic agent for AD.

[Analysis on the requirements for clinical trial protocol writing of external treatment of TCM such as tuina].

According to Standard Protocol Items: Recommendations for Interventional Trials, Consolidated Standard of Reporting Trials 2010 Statement (CONSORT), CONSORT Extension for Non-Pharmacologic Treatment Interventions (CONSORT for NPT) and Good Clinical Practice, the detailed requirements for protocol writing, reporting, and practicing of clinical trial were classified and summarized in this article. By combining the practical situation of clinical trial of external treatment of TCM such as tuina, the requirernents for clinical trial protocol writing of external treatment of TCM were analyzed and acquired which could improve the quality of clinical trial protocol of external treatment of TCM, thus to provide references for standardized execution of TMC clinical trial and reports of research results.

Obstacles to the coordination of delivering integrated prenatal HIV, syphilis and hepatitis B testing services in Guangdong: using a needs assessment approach.

BACKGROUND: Integration of services for Prevention of Mother-To-Child Transmission of HIV (PMTCT) into routine maternal and child health care is promoted as a priority strategy by the WHO to facilitate the implementation of PMTCT. Integration of services emphasizes inter-sectoral coordination in the health systems to provide convenient services for clients. China has been integrating prenatal HIV, syphilis and hepatitis B testing services since 2009. However, as the individual health systems are complex, effective coordination among different health agencies is challenging. Few studies have examined the factors that affect the coordination of such complex systems. The aim of this study is to assess the effectiveness of and examine challenges for integrated service delivery. Findings will provide the basis for strategy development to enhance the effective delivery of integrated services. METHODS: The research was conducted in Guangdong province in 2013 using a needs assessment approach that includes qualitative and quantitative methods. Quantitative data was collected through a survey and from routine monitoring for PMTCT and qualitative data was collected through stakeholder interviews. RESULTS: Routine monitoring data used to assess key indicators of coordination suggested numerous coordination problems. The rates of prenatal HIV (95%), syphilis (47%) and hepatitis B (47%) test were inconsistent. An average of only 20% of the HIV positive mothers was referred in the health systems. There were no regular meetings among different health agencies and the clients indicated complicated service processes. The major obstacles to the coordination of delivering these integrated services are lack of service resource integration; and lack of a mechanism for coordination of the health systems, with no uniform guidelines, clear roles or consistent evaluation. CONCLUSIONS: The key obstacles that have been identified in this study hinder the coordination of the delivery of integrated services. Our recommendations include: 1) Facilitate integration of the funding and information systems by fully combining the service resources of different health agencies into one unit; 2) Establish regular meetings to facilitate exchange of information and address problems; 3) Establish a client referral network between different health agencies with agreed guidelines, clear roles and consistent evaluation.

Curcumin attenuates arsenic-induced hepatic injuries and oxidative stress in experimental mice through activation of Nrf2 pathway, promotion of arsenic methylation and urinary excretion.

Oxidative stress is one of the major mechanisms implicated in inorganic arsenic poisoning. Curcumin is a natural phenolic compound with impressive antioxidant properties. What's more, curcumin is recently proved to exert its chemopreventive effects partly through the activation of nuclear factor (erythroid-2 related) factor 2 (Nrf2) and its antioxidant and phase II detoxifying enzymes. In vivo, we investigated the protective effects of curcumin against arsenic-induced hepatotoxicity and oxidative injuries. Our results showed that arsenic-induced elevation of serum alanine amino transferase (ALT) and aspartate aminotransferase (AST) activities, augmentation of hepatic malonaldehyde (MDA), as well as the reduction of blood and hepatic glutathione (GSH) levels, were all consistently relieved by curcumin. We also observed the involvement of curcumin in promoting arsenic methylation and urinary elimination in vivo. Furthermore, both the hepatic Nrf2 protein and two typically recognized Nrf2 downstream genes, NADP(H) quinine oxidoreductase 1 (NQO1) and heme oxygenase-1 (HO-1), were consistently up-regulated in curcumin-treated mice. Our study confirmed the antagonistic roles of curcumin to counteract inorganic arsenic-induced hepatic toxicity in vivo, and suggested that the potent Nrf2 activation capability might be valuable for the protective effects of curcumin against arsenic intoxication. This provides a potential useful chemopreventive dietary component for human populations.