Huangqin-Huanglian Decoction Protects Liver against Non-alcoholic Fatty Liver Disease in High Fat-diet Mice.

BACKGROUND: Traditional Chinese medicine (TCM) has the advantage of low toxicity of natural ingredients, multiple targets and effects, and low medication costs. It has unique advantages for metabolic and chronic diseases. Huangqin-Huanglian decoction (HQHLD) is composed of Scutellariae Radix, Coptidis Rhizoma, Rehmanniae Radix, and Gentianae Radix Et Rhozima; it has great potential for the treatment of NAFLD with the modern pharmacological research and TCM theory, but there is still a relative lack of research on the potential targets and pharmacological effects of HQHLD. METHODS: In this work, we have used network pharmacology to predict the targets and signaling pathways of HQHLD, and validated NAFLD-related targets using the HFD model in order to explore more therapeutic drugs and methods for NAFLD. We collected the HQHLD ingredients and NAFLD targets through TCMSP, ETCM, DisGeNET, HGMD, MalaCards, OMIM, and TTD, built ingredients-target networks by Cytoscape, and screened key ingredients in HQHLD. DAVID and Metascape databases were used for GO functional enrichment analysis and KEGG pathway enrichment analysis, respectively. Molecular docking of the key ingredients and key targets was performed by AutoDock. We verified the effect of HQHLD on high-fat diet (HFD) mice by measuring the weight, liver weight index, and the level of TG, TC, LDL-C, and HDLC. HE staining and oil-red staining were performed to detect the damage and fat accumulation in the liver. The changes in INSR, PPAR-α, PPAR-γ, TNF-α, and caspase3 were experimented with WB. RESULTS: With the network pharmacology analysis, we found quercetin, baicalein, sitosterol, wogonin, oroxylin-A, glycyrrhizin, hydroberberine, berberine, sesamin, and carotene to be the main ingredients in HQHLD. According to KEGG pathway analysis, INSR, AKT, JNK1, PPAR-α, PPAR-γ, and the other 16 targets are the main targets of HQHLD in the treatment of NAFLD. We took HFD mice as the in vivo model of NAFLD. Our results showed that HQHLD could reduce liver weight, and TG and LDL-C levels, and increase HDL-C level in serum. By HE and oil red staining, we found that HQHLD could protect the morphology of hepatocytes and reduce fat in the liver. We also found HQHLD to protect the liver by increasing the expression of INSR and PPAR-α, and reducing the expression of PPAR-γ, TNF-α, and caspase3 in the liver. CONCLUSION: In conclusion, our study has firstly studied the main ingredients and key targets of HQHDL in treating NAFLD by network pharmacology analysis, and preliminarily confirmed that HQHLD could alleviate NAFLD in a multi-target way by lowering fatty acids, and decreasing insulin resistance, inflammation, and apoptosis in the liver.

ent-Atisane Diterpenoids from Euphorbia helioscopia and Their Anti-inflammatory Activities.

Phytochemical investigation on the anti-inflammatory fraction extracted from the whole plant of Euphorbia helioscopia L. led to the isolation of three new ent-atisane diterpenoids (1-3) and five known analogues (4-8). The structures and absolute configurations of the new compounds were elucidated by comprehensive analysis of the NMR, MS, IR, ECD, and X-ray crystallography. It is worth mentioning that compound 3 belongs to a rare class of ent-atisane diterpenoid featuring a hydroxyl group at C-9. Bioactivity investigation showed that compounds 4, 7, and 8 exhibited significant inhibitory effects on LPS-induced NO production in a dose-dependent manner, which indicates their anti-inflammatory potential.

Enhancing the targeting performance and prolonging the antibacterial effects of clove essential oil liposomes to Campylobacter jejuni by antibody modification.

The application of plant essential oil liposomes to prevent and control food safety risks caused by Campylobacter jejuni (C. jejuni) still faces challenges such as lack of targeting and low release rate. Here, a bacteria-targeted and protease-activated antibacterial liposome (ACCLPs) was successfully synthesized through encapsulation of clove essential oil (CEO) by film dispersion method, embedding of casein by freeze-thaw method, and conjugation of C. jejuni antibody on the liposome membrane by post-insertion method. The average particle size, the essential oil encapsulation rate, the casein mosaic rate, and the antibody coupling efficiency of ACCLPs were determined as185.87 nm,16.9%,70.1% and 87.5%, respectively. The modification with C. jejuni antibody could significantly improve the targeting of ACCLPs to C. jejuni. Controlled release experiments showed that the exocrine protease from C. jejuni could hydrolyze the embedded casein and perforation on the ACCLPs, thus leading to a bacteria-dependent CEO release and significant prolonging the antibacterial effects of ACCLPs. Application results of ACCLPs on C. jejuni-contaminated foods showed that ACCLPs could effectively inhibit C. jejuni in a variety of meat products, fruits and vegetables and extend their shelf life without significantly affecting food quality. The results above in this work would provide a new view for the development of high efficient liposome-based antibacterial system of plant essential oil.

[Exploration on mechanism of Polygalae Radix and Acori Tatarinowii Rhizoma in treating Alzheimer's disease based on network pharmacology and experimental verification].

This study aimed to explore the action targets and mechanisms of Polygala tenuifolia and Acorus tatarinowii in treating Alzheimer's disease(AD) based on network pharmacology, molecular docking, and animal tests. The AD-related targets were collec-ted from GeneCard and the main active ingredients and targets of P. tenuifolia and A. tatarinowii from the TCMSP. Cytoscape was applied to construct the "Chinese herb-active ingredient-target-disease" network, followed by the construction of protein-protein interaction(PPI) network using STRING. GO biological function and KEGG pathway enrichment analysis was performed by DAVID and Metascape. The main active components of P. tenuifolia and A. tatarinowii and their potential core targets were docking using AutoDock Vina. The effects of P. tenuifolia and A. tatarinowii on the cognitive function were verified in mice with scopolamine(SCOP)-induced cognitive impairment. A total of seven active ingredients including kaempferol, onjixanthone Ⅰ, and marmesin and 56 potential targets of P. tenuifolia and A. tatarinowii were screened out, with the core targets covering AKT1, PTGS2, TNF, and NF-κB inflammation pathway mainly involved. The results of molecular docking also showed that the main active components of P. tenuifolia and A. tatarinowii stably bond to the core targets predicted by network pharmacology. The new object recognition experiment suggested that P. tenuifolia and A. tatarinowii improved the learning and memory abilities of mice after SCOP induction. As revealed by pathological section observation and relevant kit assay, P. tenuifolia and A. tatarinowii reduced the damage of central cholinergic neurons and enhanced the antioxidant ability of SCOP-induced mice. Western blot confirmed that P. tenuifolia and A. tatarinowii down-regulated the protein expression levels of TLR4, NF-κB, and related inflammatory factors(TNF-α, IL-1ß, and IL-6). All these have suggested that P. tenuifolia and A. tatarinowii inhibits AD via multiple components, multiple targets, and multiple pathways, which has provided an experimental basis for the clinical application of P. tenuifolia and A. tatarinowii for the treatment of AD.

Fusaricide is a Novel Iron Chelator that Induces Apoptosis through Activating Caspase-3.

Nonsmall cell lung cancer (NSCLC) has been a fatal and refractory disease worldwide. Novel therapeutic developments based on fundamental investigations of anticancer mechanisms underlie substantial foundations to win the fight against cancer diseases. In this study, we isolated a natural product fusaricide (FCD) from an endophytic fungus of Lycium barbarum, identified as Epicoccum sp. For the first time, we discovered that FCD potently inhibited proliferation in a variety of human NSCLC cell lines, with relatively less toxicity to normal cells. Our study exhibited that FCD induced apoptosis, caused DNA damage and cell cycle arrest in G0/G1 phase, and activated caspase-3 as well as other apoptosis-related factors in human NSCLC NCI-H460 cells. FCD was proven to be an iron chelator that actively decreased levels of cellular labile iron pool in NCI-H460 cells in our study. FeCl3 supplement reversed FCD-induced apoptosis. The upregulation of transferrin receptor 1 (TfR1) and downregulation of ferritin heavy chain (FTH) expression were observed after FCD treatment. In summary, our study highlighted the potential anticancer effects of FCD against human NSCLCs and demonstrated that the FCD-mediated apoptosis depended on binding to intracellular iron.

Acupoint injection combined with pelvic floor rehabilitation in the treatment of postpartum pelvic floor disorders: A protocol of randomized controlled trial.

BACKGROUND: Female pelvic floor dysfunction is one of the common chronic diseases affecting women's physical and mental health. Pregnancy and delivery are one of the main causes. Pelvic floor rehabilitation is a common method for the treatment of postpartum pelvic floor dysfunction, but it has some defects. Acupoint injection has advantages in the treatment of postpartum pelvic floor dysfunction, but there is a lack of standard clinical research to verify it. Therefore, the purpose of this randomized controlled trial is to evaluate the efficacy and safety of acupoint injection combined with pelvic floor rehabilitation in the treatment of postpartum pelvic floor disorders. METHODS: This is a prospective randomized controlled trial to study the efficacy and safety of acupoints injection combined with pelvic floor rehabilitation. And it is approved by the Ethics Committee of Clinical Research of our hospital. Patients were randomly divided into observation group (acupoint injection combined with pelvic floor rehabilitation group) or control group (pelvic floor rehabilitation group alone). The patients were followed up for 8 weeks after 12 weeks of treatment. The observation indexes included: pelvic organ prolapse degree, pelvic floor muscle strength, urinary incontinence score, adverse reactions, among others. Data were analyzed using the statistical software package SPSS version 18.0. CONCLUSIONS: This study will evaluate the efficacy and safety of acupoint injection combined with pelvic floor rehabilitation in the treatment of postpartum pelvic floor dysfunction, and provide reliable reference for the clinical application of this project. TRIAL REGISTRATION: OSF Registration number: DOI 10.17605/OSF.IO/VC65Z.

Periconceptional iron supplementation and risk of gestational diabetes mellitus: A prospective cohort study.

AIMS: Iron supplementation has been recommended for healthy pregnancy, but concerns have been raised regarding the potential adverse effects. We sought to examine the impact of periconceptional iron supplement use on subsequent gestational diabetes mellitus (GDM) risk. METHODS: Participants (N = 5101) with information on periconceptional micronutrient supplementation and diagnosis of GDM were involved. Information on iron supplementation and general characteristics were collected at enrollment and follow-up visits. GDM was diagnosed by oral glucose tolerance tests (OGTT) conducted at 24-28 weeks of gestation. Robust Poisson regression model was used to estimate the relative risks (RRs) and 95% confidence intervals (CI) for the effect of iron supplement use on GDM. RESULTS: 10.5% of the participants were diagnosed with GDM and the incidence was significantly higher in users with iron >30 mg/d for more than 3 months (Iron >30-L) than in nonusers. Adjusted RRs (95% CI) were 1.53 (1.21, 1.93) in Iron >30-L group, 1.14 (0.80, 1.61) in users with iron >30 mg/d for<3 months (Iron > 30-S) and 1.15 (0.86, 1.54) in users with iron ≤30 mg/d for any duration (Iron ≤30) respectively, compared to nonusers. This link in Iron >30-L group was even stronger (adjusted RR: 1.70, 95% CI: 1.25, 2.31) when restricting the analysis among primiparous and iron-replete participants without family history of diabetes. There were no significant differences in birth outcomes among groups. CONCLUSIONS: Periconceptional iron supplementation >30 mg/d for long-term was associated with increased GDM risk. The need and safety of prophylactic iron supplement in iron-replete pregnant women should be reconsidered.

Folic Acid Supplement Use and Increased Risk of Gestational Hypertension.

Current results regarding the effect of folic acid (FA) supplement use on gestational hypertension (GH) and preeclampsia are limited and inconsistent. We aimed to investigate whether FA supplement use was associated with GH and preeclampsia. Participants from the Tongji Maternal and Child Health Cohort with information on periconceptional FA supplement use and diagnosis of GH/preeclampsia were included (n=4853). Robust Poisson regression was used to assess the association of FA supplement use and GH and preeclampsia. Among the 4853 participants in this study, 1161 (23.9%) and 161 (3.3%) women were diagnosed with GH and preeclampsia, respectively. The risk ratio of developing GH was higher in women who used ≥800 µg/d FA supplement from prepregnancy through midpregnancy than nonusers (risk ratio, 1.33 [1.08-1.65]). After adjusting for social-demographic, reproductive, lifestyle factors, family history of hypertension, other supplement use, and gestational weight gain, the adverse association remained significant (risk ratio, 1.32 [1.06-1.64]). Restricting the analysis among women with normal weight, without family history of hypertension, and without gestational diabetes mellitus, the positive FA-GH association still existed. We did not find any significant association between FA supplement use and preeclampsia regardless of adjustment. High-dose (≥800 µg/d) FA supplement use from prepregnancy through midpregnancy was associated with increased risk of GH. Attention should be given to avoid the potential risk of GH due to inappropriate FA supplement use in women who are planning or capable of pregnancy.

Brainstem encoding of frequency-modulated sweeps is relevant to Mandarin concurrent-vowels identification for normal-hearing and hearing-impaired listeners.

F0 contours convey the primary information of lexical Tones for Mandarin Chinese, and the processing of time-varying F0 contours is important for Mandarin concurrent-vowels identification (MCVI). In this work, we examined the relationship between frequency modulation (FM) detection of auditory system and MCVI in both normal-hearing (NH) and hearing-impaired (HI) listeners. Three experiments were conducted with the same subjects to measure their MCVI, FM detection limen (FMDL), and frequency following responses (FFRs) evoked by FM sweeps, respectively. To ensure that F0 contour was the primary cue utilized, mean F0s and durations were equalized among all test vowels in the MCVI experiment. To simulate the pattern of F0 contours of Mandarin vowels, linearly FM sweeps were used as stimuli in the FMDL and FFRs experiments. The results confirmed that the performance of HI listeners was significantly worse than that of NH listeners in all of the three measurements. Besides, FFRs evoked by FM sweeps had significantly lower tracking accuracy than those evoked by steady tones only for HI listeners. The correlation analysis further revealed that any two of the three measured indices were significantly correlated when the effects of age and absolute threshold were partialed out (|r| ≥ 0.502, p ≤ 0.017). These results suggested an association between the poor performance of HI listeners in the MCVI task and their degraded auditory function on FM detection, and such a behavioral degradation has emerged in the phase-locking activity at the brainstem level.

Metformin Sensitizes Non-small Cell Lung Cancer Cells to an Epigallocatechin-3-Gallate (EGCG) Treatment by Suppressing the Nrf2/HO-1 Signaling Pathway.

Non-small cell lung cancer (NSCLC) is the most common type of lung cancer. (-)-Epigallocatechin-3-gallate (EGCG), a major polyphenol in green tea, is widely studied as a cancer chemopreventive agent with potential anti-cancer effects. The NF-E2-related factor 2 (Nrf2)/heme oxygenase-1 (HO-1) signaling pathway is considered to mediate cellular resistance to EGCG. Metformin, a classical antidiabetic drug, has been shown to prevent cancer progression. Researchers have not reported whether metformin potentiates the anti-cancer efficacy of EGCG. In this study, metformin inhibited HO-1 expression and augmented the anti-tumor effect of EGCG. Metformin also enhanced ROS (reactive oxygen species) generation induced by EGCG (100 µM), subsequently resulting in apoptosis. Based on the results of the in vivo study, size of xenografts treated with the combination of metformin and EGCG was smaller than other groups. Mechanistically, metformin modulated the EGCG-activated Nrf2/HO-1 pathway through Sirtuin 1 (SIRT1)-dependent deacetylation of Nrf2. Moreover, metformin upregulated SIRT1 expression partially through the NF-kB pathway. Comparatively, the combination of EGCG and metformin showed little impact on normal lung epithelial BEAS-2B cells. Based on our findings, metformin sensitized NSCLC cells to the EGCG treatment by suppressing the Nrf2/HO-1 signaling pathway.

[Evaluation of radionuclide therapy for the residue after surgery in papillary thyroid carcinoma].

OBJECTIVE: To assess the efficacy of radioactive iodine (RAI) for the treatment of residual papillary thyroid cancer (PTC) after surgery. METHODS: A total of 20 patients diagnosed with PTC and underwent 2-6 courses of RAI therapy for residual PTC after surgery in other hospitals were included our study. Of these, 13 were in stage I, 3 in stage III and 4 in stage IV. All the cases were operated again due to the presence of suspicious residual tumors indicated by CT. Excision of thyroid tumor residue was performed in 5 cases and neck dissection in 15 cases (20 sides). The suspicious thyroid or neck residual tumors were examined pathologically after surgery. Response Evaluation Criteria in Solid Tumors (RECIST) was used to evaluate the efficacy of surgery treatment on residual tumor. T-test was used to identify variables associated to RAI and to calculate the propensity score to receive RAI after surgery. RESULTS: The patients aged 22-58 years, with a median age of 40 years. The mean times of surgeries received before RAI was 1.5 and the mean dose of applied RAI was 318 mCi (210-660 mCi). No significant difference in tumor size between pre-RAI and post-RAI was found (t = 1.177, P > 0.05). With postoperative pathological examination, the suspicious thyroid or neck residual tumors were confirmed as PTC or the cervical lymph metastasis of PTC. CONCLUSIONS: For the residue or metastasis of PTC after operation, reoperation should be a priority, while RAI therapy has no obvious therapeutic effect and it should be limited to selected cases such as those with distant metastasis or unsuitable for operation but with iodine uptake function, or taken as an adjuvant treatment after radical resection of cervical lesions.