Landscape changes and livelihood outcomes in rural tea farming communities: A case study in Fuding City, Fujian Province, Southeast China.

Landscape changes driven by cash crop plantations have been prevalent in tropical and subtropical regions worldwide in recent decades. Investigating the landscape changes and concluding livelihood outcomes are fundamental to figure out the solutions for rural sustainability. This paper examined the landscape changes which was caused by land use changes in tea plantations as well as investigated the resultant livelihood impacts, based on a case study in Fuding City, Southeast China. A questionnaire survey of 114 rural households in four sampled villages was conducted. Results demonstrated that expansion and intensification of tea plantations were two major proximate causes of landscape changes in recent decade. Our survey indicated that some existing intensively-managed tea plantations had derived from intensification and expansion of tea plantations, respectively. We identified four underlying driving forces of landscape changes, including economic benefit, governmental policies, wildlife destruction on grain crops, and rural return migration. Our study confirmed that landscape changes have significant positive effects on farmers' livelihoods, including increasing employment and incomes, raising living standards, enhancing livelihood assets and livelihood sustainability. Especially, the aged rural populations could have a relatively decent living standard. Meanwhile, the excessive expansion of tea plantations may impair livelihood resilience. Lastly, three policy suggestions based on different time scales have been put forward to promote rural households' livelihood sustainability and resilience.

Sarcopenia assessed by computed tomography or magnetic resonance imaging is associated with the loss of response to biologic therapies in adult patients with Crohn's disease.

Sarcopenia occurs in patients with Crohn's disease (CD). However, the association between sarcopenia and loss of response (LOR) to biologic agents remains unclear. This study explored such an association in CD patients. This retrospective study included 94 CD patients who received biologic therapy. The skeletal muscle cross-sectional area at the third lumbar was assessed by computed tomography or magnetic resonance imaging for sarcopenia evaluation. A LOR was defined by fecal calprotectin (FC) < 250 µg/g or >50% reduction from baseline levels or other factors, such as the used agent being replaced by other biologic agents. The association between sarcopenia and LOR was assessed by logistic regression analysis. LOR was observed in 54 patients (57.4%). The prevalence of sarcopenia in the LOR group was higher than that in response group (70.4% vs. 40.0%, p = 0.003). Sarcopenia (odds ratio [OR] = 3.89, 95% confidence interval [CI]: 1.31-11.54), Montreal L1 type (OR = 0.20, 95% CI: 0.06-0.60), perianal lesions (OR = 4.08, 95% CI: 1.31-12.70), and monocytes percentage (OR = 1.27, 95% CI: 1.02-1.57) at baseline were independent associated factors for LOR. Sarcopenia was also associated with LOR in patients who received infliximab (OR = 3.31, 95% CI: 1.11-9.87). Montreal L1 type, perianal lesions, and monocytes percentage (Model 1), and with additional consideration of sarcopenia (Model 2), were developed to predict LOR. Model 2 showed better performance than Model 1 (area under the curve [AUC] 0.82 vs. 0.75). Sarcopenia was associated with the LOR to biological agents or infliximab in adult patients with CD.

Pinostrobin from plants and propolis against human coronavirus HCoV-OC43 by modulating host AHR/CYP1A1 pathway and lipid metabolism.

Coronaviruses, as enveloped positive-strand RNA viruses, manipulate host lipid compositions to enable robust viral replication. Temporal modulation of the host lipid metabolism is a potential novel strategy against coronaviruses. Here, the dihydroxyflavone pinostrobin (PSB) was identified through bioassay that inhibited the increment of human coronavirus OC43 (HCoV-OC43) in human ileocecal colorectal adenocarcinoma cells. Lipid metabolomic studies showed that PSB interfered with linoleic acid and arachidonic acid metabolism pathways. PSB significantly decreased the level of 12, 13- epoxyoctadecenoic (12, 13-EpOME) and increased the level of prostaglandin E2. Interestingly, exogenous supplement of 12, 13-EpOME in HCoV-OC43-infected cells significantly stimulated HCoV-OC43 virus replication. Transcriptomic analyses showed that PSB is a negative modulator of aryl hydrocarbon receptor (AHR)/cytochrome P450 (CYP) 1A1signaling pathway and its antiviral effects can be counteracted by supplement of FICZ, a well-known AHR agonist. Integrative analyses of metabolomic and transcriptomic indicated that PSB could affect linoleic acid and arachidonic acid metabolism axis through AHR/CYP1A1 pathway. These results highlight the importance of the AHR/CYP1A1 pathway and lipid metabolism in the anti-coronavirus activity of the bioflavonoid PSB.

Neoline, fuziline, songorine and 10-OH mesaconitine are potential quality markers of Fuzi: In vitro and in vivo explorations as well as pharmacokinetics, efficacy and toxicity evaluations.

ETHNOPHARMACOLOGICAL RELEVANCE: Fuzi, the lateral roots of Aconitum carmichaelii Debx, plays an irreplaceable role in treating Yang deficiency and cold coagulation syndromes. However, Fuzi has a narrow margin of safety since its pharmacological constituents, Aconitum alkaloids, have potential cardiotoxicity and neurotoxicity. The current quality markers (Q-markers) for the control of Fuzi's efficacy and toxicity are 3 monoester-diterpenoid alkaloids, namely, benzoylaconine (BAC), benzoylhypaconine and benzoylmesaconine (BMA) and 3 diester-diterpenoid alkaloids, namely, aconitine (AC), hypaconitine and mesaconitine (MA). However, mounting evidence indicates that the current 6 Q-markers may not be efficacy- or toxicity-specific enough for Fuzi. AIM OF THE STUDY: The aim of this study was to explore and evaluate efficacy- or toxicity-specific potential quality markers (PQ-markers) of Fuzi. MATERIALS AND METHODS: PQ-markers were explored by analyzing 30 medicinal samples and alkaloids exposed in mouse. Pharmacokinetics of PQ-markers on C57BL/6J mice were determined. Anti-inflammatory effects of PQ-markers were evaluated by λ-carrageenan-induced paw edema model and lipopolysaccharide-induced RAW264.7 cell inflammatory model, while analgesic effects were assessed by acetic acid-induced pain model and Hargreaves test. Cardiotoxicity and neurotoxicity of PQ-markers were assessed by histological and biochemical analyses, while acute toxicity was evaluated by modified Kirschner method. RESULTS: After in vitro and in vivo explorations, 7 PQ-markers, namely, neoline (NE), fuziline (FE), songorine (SE), 10-OH mesaconitine (10-OH MA), talatizamine, isotalatizidine and 16ß-OH cardiopetalline, were found. In the herbal medicines, NE, FE, SE and 10-OH MA were found in greater abundance than many other alkaloids. Specifically, the amounts of NE, FE and SE in the Fuzi samples were all far higher than that of BAC, and the contents of 10-OH MA in 56.67% of the samples were higher than that of AC. In mouse plasma and tissues, NE, FE, SE, talatizamine, isotalatizidine and 16ß-OH cardiopetalline had higher contents than the other alkaloids, including the 6 current Q-markers. The pharmacokinetics, efficacy and toxicity of NE, FE, SE and 10-OH MA were further evaluated. The average oral bioavailabilities of NE (63.82%), FE (18.14%) and SE (49.51%) were higher than that of BMA (3.05%). Additionally, NE, FE and SE produced dose-dependent anti-inflammatory and analgesic effects, and their actions were greater than those of BMA. Concurrently, the toxicities of NE, FE and SE were lower than those of BMA, since no cardiotoxicity or neurotoxicity was found in mice after NE, FE and SE treatment, while BMA treatment notably increased the creatine kinase activity and matrix metalloproteinase 9 level in mice. The average oral bioavailability of 10-OH MA (7.02%) was higher than that of MA (1.88%). The median lethal dose (LD50) of 10-OH MA in mice (0.11 mg/kg) after intravenous injection was close to that of MA (0.13 mg/kg). Moreover, 10-OH MA produced significant cardiotoxicity and neurotoxicity, and notable anti-inflammatory and analgesic effects that were comparable to those of MA. CONCLUSIONS: Seven PQ-markers of Fuzi were found after in vitro and in vivo explorations. Among them, NE, FE and SE were found to be more efficacy-specific than BMA, and 10-OH MA was as toxicity-specific as MA.

High-performance liquid chromatography micro-fraction bioactive evaluation combined with countercurrent chromatographic separation of antioxidants from Citrus peel and their tyrosinase inhibition activities.

In the present study, high-performance liquid chromatography micro-fraction bioactive evaluation and high speed countercurrent chromatography were performed on screening, identification and isolation of antioxidants from Citrus peel. Three compounds were screened as antioxidants and tyrosinase inhibitors using 2,2'-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation scavenging assay and tyrosinase activity test, then they were identified as eriocitrin, narirutin and hesperidin. Moreover, the solvent system ethyl acetate-n-butanol-water (6:4:10, v/v/v) was used for separation of ethyl acetate extract of Citrus peel by high speed countercurrent chromatography. In total, 0.45 mg of eriocitrin with 87.10% purity, 2.04 mg of narirutin with 95.19% purity and 1.35 mg of hesperidin with 95.19% purity were obtained from 20 mg of ethyl acetate extract of Citrus peel in a single run and then each component was subjected to 2,2'-azino-bis (3-ethyl-benzothiazoline-6-sulfonic acid) radical cation scavenging assay and tyrosinase inhibition assay. Eriocitrin showed great antioxidant activity (the half-maximum concentration: 3.65 µM) and tyrosinase inhibition activity (the half-maximum concentration: 115.67 µM), while narirutin and hesperidin exhibited moderate activity. Tyrosinase inhibition activity for eriocitrin in vitro was reported for the first time. Furthermore, molecular docking between eriocitrin and mushroom tyrosinase was also studied.

Acupuncture for chronic tinnitus: A CARE-compliant case report.

INTRODUCTION: Tinnitus is a sound hallucination characterised by buzzing and hissing in the ear or brain of a patient in the absence of an externally available sound source. It could be perceived as one or more sounds and can last for a certain period of time. OBJECTIVE: We aimed to report the successful treatment of tinnitus using acupuncture. METHOD: A patient diagnosed with chronic tinnitus had buzzing sounds in both ears for over 4 years. Acupuncture treatment was administered a total of five times. GV20 (Baihui), EX-HN1 (Sishencong), GV24 (Shenting), CV12 (Zhongwan), CV10 (Xiawan), CV6 (Qihai), CV4 (Guanyuan), and other bilateral acupuncture points, including GB13 (Benshen), SI19 (Tinggong), GB2 (Tinghui), SJ17 (Yifeng), KI19 (Yindu), and KI17 (Shangqu), were selected as acupuncture points. RESULTS: Tinnitus was successfully resolved, and THI scores decreased. CONCLUSIONS: Acupuncture is a potential alternative treatment for chronic tinnitus.

Risk factors for the postoperative bladder neck contracture in patients with small-volume prostatic hyperplasia.

OBJECTIVE: This study was to explore the risk factors for postoperative bladder neck contracture (BNC) after transurethral operation of prostate in patients with small-volume prostatic obstruction. METHODS: Clinicopathologic data at our center from February 2016 to January 2020 were retrospectively collected and analyzed. Clinicopathological characteristics between patients with and without BNC were compared. Multivariate logistic regression was used to determine the risk factors for postoperative BNC. RESULTS: There were a total of 39 patients (8.53%) with postoperative BNC. Multivariate logistic regression analysis demonstrated that preoperative bladder neck diameter (BND), intravesical prostatic protrusion (IPP), surgical methods (transurethral resection of prostate (TURP)/anatomical endoscopic enucleation of the prostate (AEEP)), and postoperative urinary tract infection (UTI) were independent risk factors for postoperative BNC in patients with small-volume prostatic obstruction (P < 0.05). The incidence of postoperative BNC in patients undergoing AEEP was significantly decreased compared with those undergoing TURP. The optimal cut-off value of preoperative IPP was 6.10 mm while the optimal cut-off value of preoperative BND was 2.52 cm. CONCLUSIONS: Larger preoperative bladder neck and higher preoperative IPP lead to decreased incidence of postoperative BNC in patients with small-volume prostatic obstruction. Active management of postoperative UTI could effectively prevent the occurrence of postoperative BNC. Compared with TURP, complete AEEP would contribute to reduce BNC in patients with small-volume prostatic obstruction.

Exosome-like nanovesicles derived from Phellinus linteus inhibit Mical2 expression through cross-kingdom regulation and inhibit ultraviolet-induced skin aging.

BACKGROUND: Phellinus linteus (PL), which is a typical medicinal fungus, has been shown to have antitumor and anti-inflammatory activities. However, studies on the effect of anti-photoaging are limited. Studies have shown that exosome-like nanovesicles are functional components of many medicinal plants, and miRNAs in exosome-like nanovesicles play a cross-kingdom regulatory role. At present, research on fungi exosome-like nanovesicles (FELNVs) is few. RESULTS: We systematically evaluated the anti-aging effects of PL. FELNVs of PL were isolated, and the functional molecular mechanisms were evaluated. The results of volunteer testing showed that PL had anti-aging activity. The results of component analysis showed that FELNVs were the important components of PL function. FELNVs are nanoparticles (100-260 nm) with a double shell structure. Molecular mechanism research results showed that miR-CM1 in FELNVs could inhibit Mical2 expression in HaCaT cells through cross-kingdom regulation, thereby promoting COL1A2 expression; inhibiting MMP1 expression in skin cells; decreasing the levels of ROS, MDA, and SA-ß-Gal; and increasing SOD activity induced by ultraviolet (UV) rays. The above results indicated that miR-CM1 derived from PL inhibited the expression of Mical2 through cross-kingdom regulation and inhibited UV-induced skin aging. CONCLUSION: miR-CM1 plays an anti-aging role by inhibiting the expression of Mical2 in human skin cells through cross-species regulation.

A Strategy for Pinpointing Natural Bioactive Components Using Two-Dimensional Bioassay Profilings Combined with Comprehensive Two-Dimensional Countercurrent Chromatography × High-Performance Liquid Chromatography.

Inspired by the interpretation of two-dimensional (2D) nuclear magnetic resonance spectra, an efficient strategy was proposed for pinpointing bioactive components from complex natural products. An off-line comprehensive countercurrent chromatography (CCC) × high-performance liquid chromatography (HPLC) was employed to achieve a 2D chemical chromatogram, and 2D bioassay profilings were obtained from bioassays of the eluent of the first dimension (1D) CCC and the eluent of the second dimension (2D) HPLC. Then 2D chemical chromatograms and 2D bioassay profilings were matched for pinpointing bioactive natural components from complex matrices. Thus, bioactive components in a complex matrix could be efficiently analyzed, separated, and bioactivity-determined. This experimental scheme was successfully demonstrated with a traditional medicinal herb Polygonum cuspidatum Sieb. et Zucc. The feasibility of this 2D strategy was verified with tyrosinase inhibition assay, α-glucosidase inhibition assay, DPPH radical scavenging assay, and ABTS•+ decolorization assay. Eight natural inhibitors were successfully pinpointed and identified from P. cuspidatum. Both pieceid-2″-O-gallate (10) and vanicoside B (20) were screened and identified as natural tyrosinase inhibitors for the first time. Meanwhile, vanicoside B (20) was also found as the strongest α-glucosidase inhibitor among all the isolated components. Most of the compounds exhibited much higher radical scavenging activities. Compared with traditional methodology based on one-dimensional chromatographic separation, the present 2D strategy would be more precise, efficient, and convenient to screen and separate bioactive compounds from complex matrices.

Legumain affects the PI3K/AKT tumor progression pathway in retinoblastoma.

Known as a common malignant tumor among children, retinoblastoma (RB) is highly malignant and has poor prognosis, damages children's vision and degrades quality of life. To identify a potential molecular mechanism of RB, we conducted this study on legumain (LGMN), which is highly expressed in multiple tumors. In this study, we found that LGMN was significantly upregulated in RB cells and was positively expressed in RB tissues. We confirmed that LGMN overexpression (LGMN-OE) can promote RB cell proliferation and inhibit cell apoptosis through CCK8 experiments and flow cytometry. In addition, real-time quantitative polymerase chain reaction (RT‒qPCR) and Western blot results showed that LGMN-OE could regulate the expression of epithelial-mesenchymal transformation-related genes and proteins, related to tumor invasion and metastasis. Moreover, after LGMN knock down, the result was the opposite., RNA sequence analysis revealed 1159 differentially expressed genes between LGMN-OE and the negative control (NCOE), of which 564 were upregulated and 595 were downregulated. The first 10 genes were verified by RT‒qPCR based on P value and fold change. Interestingly, we found that LGMN could regulate the expression of recoverin (RCVRN)through a gene responsible for cancer-related retinopathy. We also screened and verified that LGMN partially activated the PI3K/AKT pathway in RB. Furthermore, we evaluated the effect of legumain inhibitors (e.g., esomeprazole) on RB, and the results suggest that esomeprazole may provide a reference for the clinical adjuvant treatment of RB. In conclusion, legumain can serve as an attractive target for RB therapy and hopefully provide new insights and ideas for the development of targeted drugs and precise personalized clinical therapy.

Establishment and Evaluation of Influencing Factors and Risk Prediction Model of Severe Neonatal Hyperbilirubinemia Complicated with Acute Bilirubin Encephalopathy.

Objective: To explore the influencing factors of severe hyperbilirubinemia in neonates complicated with acute bilirubin encephalopathy (ABE) and then build relevant prediction models and evaluate the prediction performance of the models. Methods: The data of 120 neonates with severe hyperbilirubinemia were collected by retrospective analysis. Univariate and multivariate analysis methods were used to analyze the data of 120 children. R software was used to visualize the results of multivariate analysis, and a nomogram model was obtained. The receiver operating characteristic curve (ROC), calibration curve, and decision-making curve (DC) were used to evaluate the discrimination, accuracy, and clinical net profit rate of the model. Results: Multivariate analysis showed that nonfull breastfeeding, high-risk symptoms, and pregnancy complications were independent risk factors for ABE in neonates with severe hyperbilirubinemia. At the same time, the risk of ABE in neonates with severe hyperbilirubinemia increased with the increase of B/A and Hb levels. The ROC curve showed that the area under the curve for the model was 0.908 (95% CI: 0.839-0.960). The calibration curve shows that the actual prediction curve of the model is in good agreement with the corrected prediction curve. Using the cutoff value of the ROC curve as the diagnostic criterion, the threshold probability of the model was calculated to be 38%. The decision curve shows that when 38% is used as the basis for judging whether to take measures to intervene, the profit rate is 61%. Conclusion: The occurrence of ABE in neonates with severe hyperbilirubinemia is affected by many factors, and there is a certain degree of interaction between these factors. Combining multiple factors to construct a risk nomogram model can provide a reference for early clinical detection of high-risk neonates.

Multi-target mechanisms against coronaviruses of constituents from Chinese Dagang Tea revealed by experimental and docking studies.

ETHNOPHARMACOLOGICAL RELEVANCE: The leaves of Eurya chinensis（Chinese Dagang Tea）have been consumed as herbal tea for centuries in Guangdong, China, and have also been used to prevent influenza and treat colds and fevers in traditional Chinese medicine. However, there are no reports on the chemical profile and efficacy of its leaves for the treatment of fever and viral infections. MATERIALS AND METHODS: The chemical constituents of Eurya chinensis leaves were isolated and identified by phytochemical study and spectroscopic data, E. chinensis extracts and compounds were evaluated for their antiviral activities by cytopathic effect (CPE) reduction and antibody-based EC50 assay. The antiviral effect of the main component was confirmed by immunofluorescence and transmission electron microscopy. Virtual screening and docking enzyme inhibition experiments were performed to analyze the anti-coronavirus mechanisms of the compounds from E. chinensis leaves. RESULTS: In this study, we found for the first time that E. chinensis leaf extract exhibited inhibitory effects against coronaviruses HCoV-OC43 in vitro. Among 23 monomer compounds isolated from E. chinensis leaf extract, the triterpenoids (betulinic acid, α-amyrin) and the flavonoids (naringenin, eriodictyol and quercetin) showed marked antiviral activity. Microscopic optical analyses further demonstrated that betulinic acid can remove virus particles from HCoV-OC43 infected cells. Virtual screening and docking analysis towards the coronavirus in vogue revealed that betulinic acid was able to bind well to PLpro and Nsp14N7-MTase, and that the flavonoids prefer to bind with PLpro, Nsp3MES, NspP14N7-MTase, Nsp16GTA, and Nsp16SAM. The enzyme inhibition experiments demonstrated that betulinic acid (1) exhibited significant inhibition of PLpro and N7-MTase activity of SARS-CoV-2. CONCLUSION: This study proposes E. chinensis and its triterpenoids and flavonoids as promising potential treatments for coronaviruses.

Selenium Deficiency Leads to Changes in Renal Fibrosis Marker Proteins and Wnt/ß-Catenin Signaling Pathway Components.

Renal fibrosis is the final result of the progression of chronic kidney disease (CKD) to end-stage renal disease (ESRD). Earlier studies confirmed that selenium (Se) displays a close association with kidney diseases. However, the correlation between Se and fibrosis has rarely been explored. Thus, this article mainly aimed to investigate the effect of Se deficiency on renal fibrosis and the Wnt/ß-catenin signaling pathway. Twenty BALB/c mice were fed a diet containing 0.02-mg/kg Se (Se-deficient diet) or 0.18-mg/kg Se (standard diet) for 20 weeks. A human glomerular mesangial cell (HMC) cell line was transfected with lentiviral TRNAU1AP-shRNA vector to establish a stable Se deficiency model in vitro. As indicated in this study, the glutathione (GSH) content in the Se-deficient group displayed an obvious decline compared with that in the control group, whereas the content of malondialdehyde (MDA) was obviously elevated. The results of Masson staining showed fibrosis around the renal tubules, and the results of immunohistochemistry showed that the area of positive fibronectin expression increased. In the Se-deficient group, the levels of collagen I, collagen III, matrix metalloproteinase 9 (MMP9), and other fibrosis-related proteins changed significantly in vivo and in vitro. Compared with the control group, the TRNAU1AP-shRNA group showed markedly reduced cell proliferation and migration abilities. Our data indicate that Se deficiency can cause kidney damage and renal fibrosis. Furthermore, the Wnt pathway is critical for the development of tissue and organ fibrosis. The data of this study demonstrated that the expression of Wnt5a, ß-catenin, and dishevelled 1 (Dvl-1) was significantly upregulated in the Se-deficient group. Therefore, the Wnt/ß-catenin pathway may play an important role in renal fibrosis caused by Se deficiency.

Solvent strength of aqueous phase for two typical biphasic solvent systems in high-speed countercurrent chromatography.

In the present work, influence of solvent strength of aqueous phase for two frequently-used biphasic solvent system in partition coefficient (K) of selected solutes were mainly studied, and a new method for selection of biphasic solvent system was proposed for high-speed countercurrent chromatographic separations. Solvent strength was referred to the typical theory that was deeply investigated in conventional reversed-phase liquid chromatography. Experimental results showed that a linear relationship between log(K) of solutes and apparent content of methanol in biphasic solvent system was found for the biphasic solvent system hexane-ethyl acetate-methanol-water (HEMWat), which was consistent with the relationship between real content and apparent content of methanol in this system. Meanwhile, a quadratic relationship was found between log(K) of solutes and apparent content of methanol in biphasic solvent system chloroform-methanol-water (ChMWat), in which it was found that the relationship between real content and apparent content of methanol in this system was also quadratic. In addition, a visual and simple method was proposed to select a suitable biphasic solvent system for separation of target compounds by high-speed countercurrent chromatography with isocratic elution, which saves a lot of manpower and material resources in order to find a suitable two-solvent system. An optimal biphasic solvent system for isolation of several tested compounds by high-speed countercurrent chromatography was easily obtained using our proposed method.

Progressive Study on the Non-thermal Effects of Magnetic Field Therapy in Oncology.

Cancer is one of the most common causes of death worldwide. Although the existing therapies have made great progress and significantly improved the prognosis of patients, it is undeniable that these treatment measures still cause some serious side effects. In this context, a new treatment method is needed to address these shortcomings. In recent years, the magnetic fields have been proposed as a novel treatment method with the advantages of less side effects, high efficiency, wide applications, and low costs without forming scars. Previous studies reported that static magnetic fields (SMFs) and low-frequency magnetic fields (LF-MFs, frequency below 300 Hz) exert anti-tumor function, independent of thermal effects. Magnetic fields (MFs) could inhibit cell growth and proliferation; induce cell cycle arrest, apoptosis, autophagy, and differentiation; regulate the immune system; and suppress angiogenesis and metastasis via various signaling pathways. In addition, they are effective in combination therapies: MFs not only promote the absorption of chemotherapy drugs by producing small holes on the surface of cell membrane but also enhance the inhibitory effects by regulating apoptosis and cell cycle related proteins. At present, MFs can be used as drug delivery systems to target magnetic nanoparticles (MNPs) to tumors. This review aims to summarize and analyze the current knowledge of the pre-clinical studies of anti-tumor effects and their underlying mechanisms and discuss the prospects of the application of MF therapy in cancer prevention and treatment.

Selenium Deficiency-Induced Damage and Altered Expression of Mitochondrial Biogenesis Markers in the Kidneys of Mice.

Previous studies have raised concerns that kidney disease is often closely related to low serum Se levels in patients and that hyposelenemia may increase the vulnerability of patients to complications. However, few studies examining renal injury caused by Se deficiency have been conducted. To determine the effects of a selenium-deficient diet on renal function, a mouse model was fed a selenium-deficient diet (0.02 mg Se/kg) for 20 weeks. Meanwhile, mice in the control group (selenium-adequate) were fed a standard diet (0.18 mg Se/kg). The cellular models were established by lentiviral Trnau1ap-shRNA vectors transfected into mouse podocyte (MPC5) and mouse renal tubular epithelial (TCMK1) cell lines. Significant increases in serum creatinine levels and urinary protein/creatinine ratios were accompanied by increased MDA content in the Se-deficient group compared to the control group. The morphological observations of tissues showed widespread inflammation and ultrastructural changes in the Se-deficient group, such as swollen mitochondria and extensive podocyte fusion and renal tubular microvilli shedding. In addition, the expression of COXIV and cytochrome c was significantly downregulated in the Se-deficient group. Importantly, the mRNA levels of silent mating type information regulation 2 homolog 1 (SIRT1) and peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α) and the protein levels of SIRT1 were increased in the Se-deficient group compared with the normal control group. Our data indicate that Se deficiency induces renal injury in mice. The elevated oxidative stress caused by Se deficiency may result in mitochondrial damage, which might affect renal function. Moreover, the SIRT1/PGC1α axis likely plays an important role in the compensatory mechanism of mitochondrial dysfunction.

Ultrasonicated sour Jujube seed flavonoids extract exerts ameliorative antioxidant capacity and reduces Aß-induced toxicity in Caenorhabditis elegans.

ETHNOPHARMACOLOGICAL RELEVANCE: Sour Jujube seed from Ziziphus jujuba Mill. var. Spinosa (Bunge) Hu ex H. F. Chow is a traditional Chinese herb. It was demonstrated with significant activities in anti-depression and antioxidant by numerous pharmacological studies. Flavonoids is one of the main constituents in sour Jujube seed. AIM OF THE STUDY: The aim of this study was to propose a green ultrasound-assisted extraction (UAE) process of flavonoids from sour Jujube seed. MATERIALS AND METHODS: The extraction parameters were investigated and optimized using single factor experiments, Plackett-Burman design (PBD) and response surface methodology (RSM). Moreover, a comparative analysis between ultrasound-assisted extraction and heat reflux extraction was performed to verify the ameliorating effects of ultrasound-assisted extraction on the flavonoids yield, the composition, antioxidant capacities in vitro and ROS scavenging capacity in PC12 cells. Meanwhile, the effects of flavonoids extract (FE) on Aß transgenic Caenorhabditis elegans (GMC101) behavior were investigated. RESULTS: The optimal extracting conditions of total flavonoids were as follows: ethanol concentration 70.60 (v/v%), liquid-solid ratio 15.02:1 mL/g, ultrasonic power 404 W, extraction time 60.03 min. The highest extraction yield was 1.59%. When compared to Heat reflux extraction (HRE) that only has gained a yield of 1.356%. Approximately, the UAE method was able to increase the yield by 17.11%. Moreover, FE extracted by UAE displayed larger capacity of scavenging ABTS, DPPH, superoxide, and hydroxyl radicals and reducing the level of ROS accumulation in PC12 cells, suggesting the biological functions of these compounds could be also better protected under UAE conditions. Furthermore, FE could also increase the chemotaxis and heat stress resistance ability, delay the paralysis and extend the lifespan of Caenorhabditis elegans. CONCLUSION: UAE is a green and efficient technique for the preparation of flavonoids from sour Jujube seed. The flavonoids extract can reduce Aß-induced toxicity in Caenorhabditis elegans.

YY1 Complex Promotes Quaking Expression via Super-Enhancer Binding during EMT of Hepatocellular Carcinoma.

Quaking (QKI) is an alternative splicing factor that can regulate circRNA formation in the progression of epithelial-mesenchymal transition, but the mechanism remains unclear. High expression of QKI is correlated with short survival time, metastasis, and high clinical stage and pathology grade in hepatocellular carcinoma (HCC). Here we report that transcription of the QKI gene was activated by the Yin-Yang 1 (YY1)/p65/p300 complex, in which YY1 bound to the super-enhancer and promoter of QKI, p65 combined with the promoter, and p300 served as a mediator to maintain the stability of the complex. This YY1/p65/p300 complex increased QKI expression to promote the malignancy of HCC as well as an increased circRNA formation in vitro and in vivo. Hyperoside is one of several plant-derived flavonol glycoside compounds. Through virtual screening and antitumor activity analysis, we found that hyperoside inhibited QKI expression by targeting the YY1/p65/p300 complex. Overall, our study suggests that the regulatory mechanism of QKI depends on the YY1/p65/p300 complex and that it may serve as a potential target for treatment of HCC. SIGNIFICANCE: These findings identify the YY1/p65/p300 complex as a regulator of QKI expression, identifying several potential therapeutic targets for the treatment of HCC.

CCM111 prevents hepatic fibrosis via cooperative inhibition of TGF-ß, Wnt and STAT3 signaling pathways.

CCM111 is an aqueous extract of Antrodia cinnamomea (AC) that has exhibited anti-liver fibrosis functions. However, the detailed mechanisms of AC action against liver fibrosis have not been elucidated yet. The present research showed that CCM111 significantly lowered the levels of the hepatic enzyme markers glutamate oxaloacetate transaminase (GOT) and glutamic pyruvic transaminase (GPT), prevented liver damage and collagen deposition, and downregulated TGF-ß/Smad signaling in a dose-dependent manner compared with CCl4 treatment alone. CCM111 markedly inhibited TGF-ß, Wnt and STAT3 signaling pathway-regulated downstream genes in the liver by next-generation sequencing. The antifibrotic mechanisms of CCM111 were further demonstrated in HSC-T6 cells. Our data demonstrated for the first time that CCM111 can protect against CCl4-induced liver fibrosis by the cooperative inhibition of TGF-ß-, Wnt- and STAT3-dependent proinflammatory and profibrotic mediators, suggesting that CCM111 might be a candidate for preventing and treating chronic fibrotic liver diseases.

[Study of heterologous efficient synthesis of cucurbitadienol].

Cucurbitadienol has anti-inflammation, anti-cancer activities, and acts as a precursor of traditional Chinese medicine active ingredients mogroside and cucurbitacine. For construction of a Sacchromyces cerevisiae cell factory for production of cucurbitadienol, we firstly cloned a cucurbitadienol synthase (CBS) gene from Siraitia grosvenorii. Then, through heterologous expression of CBS in the triterpenoid chassis strain WD-2091, the engineered strain could produced 27.44 mg•L ⁻¹ cucurbitadienol, which was determined by GC-MS. Further regulation of CBS expression led to cucurbitadienol's titer increasing by 202.07% and reaching 82.89 mg•L ⁻¹ in the shake flask fermentation and 1 724.10 mg•L ⁻¹ in the high cell density fermentation. Our research promotes the cucurbitane-type tetracyclic triterpenoids synthesis pathway analysis progress and provides the basis for further obtaining cell factories for production of cucurbitadienol tetracyclic triterpenoids.