The photocatalytic reduction of U(VI) by Ag-doped SnS2 materials under visible light.

Efficient degradation of uranium(VI) (U(VI)) in wastewater is an urgent problem because of the chemical toxicity and radiotoxicity. In this study, the Agx-SnS2 photocatalysts were compounded by a simple hydrothermal method, effectively removing U(VI) under visible light in water. Compared with SnS2, the results indicated that Agx-SnS2 would decrease the crystallinity without destroying the crystal structure. Moreover, it has excellent photocatalytic performance on the degradation rate of U(VI). Ag0.5-SnS2 exhibited a prominent photocatalytic reduction efficiency of UO22+ of about 86.4% under optical light for 75 min. This was attributed to Ag-doped catalysts, which can narrow the band gap and enhance absorption in visible light. Meanwhile, the doping of Ag promoted the separation of photoinduced carriers, so that more photogenerated charges participated in the photocatalytic reaction. The stability and reusability were verified by the cycle test and the potential photocatalytic mechanism was analyzed based on the experiment.

Analyze and simulate an individualized nutritional computing system for multidisciplinary teams in nutritional support therapy.

To explore the efficiency of nutritional support therapy . Pharmacists led the construction of an individualized nutritional computing system and were involved in the process of treatment. After obtaining relevant professional knowledge and instruction on how to operate the system, MDT members intervened in the incorrect treatment process during nutritional support therapy. The Department of Radiation Oncology and the Intensive Care Unit (ICU) were selected as pilot departments to compare and analyze the rationality of nutrition risk screening and the use of enteral nutrition (EN) and parenteral nutrition (PN) in treatment before and after intervention. The individualized nutritional computing system significantly improved work efficiency, promoted nutrition risk screening, and saved 10-15 minutes in the treatment of each patient. After intervention in the Department of Radiation Oncology, the use rate of Total Nutrient Admixture (TNA) increased by 7.17%, and the single-bottle infusion rate of PN preparation decreased by 17.94% in patients at risk of malnutrition. The use rate of EN and single-bottle infusion rate of PN preparation in patients without risk of malnutrition decreased by 15.17% and 20.81%, respectively. Overall, 98.75% of ICU patients were at risk of malnutrition. The use rates of EN and TNA increased by 12.79% and 12.14%, respectively, and the single-bottle infusion rate of PN preparation decreased by 10.06%. Streamlined and mobile MDT, the use of an individualized nutritional computing system, and the effective work of pharmacists in the process significantly improved the efficiency and rationality of nutritional support therapy .

W/O/W emulsions stabilized with whey protein concentrate and pectin: Effects on storage, pasteurization, and gastrointestinal viability of Lacticaseibacillus rhamnosus.

Probiotics have demonstrated various bioactive functions but poor storage and application stability, and encapsulation a promising method of increasing its viability. In this study, whey protein concentrate (WPC) and pectin (PEC) formed non-covalent complexes through electrostatic interaction at pH 3.0. The formed WPC-PEC complexes showed superior particle size, absolute potential, emulsification properties, and structural changes when PEC concentration was >0.8 % (w/v). This made them appropriate as a hydrophilic emulsifier to stabilize W/O/W emulsions. Then, Lacticaseibacillus rhamnosus, one representative of probiotics, was encapsulated in the internal aqueous phase of W/O/W emulsions. We obtained higher encapsulation efficiency (78.49 %) and smaller D4,3 (9.72 µm) with 0.8 % (w/v) PEC concentration. Encapsulation of Lacticaseibacillus rhamnosus in W/O/W emulsions improved its viability under harsh conditions, including 28 days storage at 4 °C, simulated pasteurization, and simulated gastrointestinal digestion. W/O/W emulsions stabilized by WPC-PEC non-covalent complexes further improved the survival of Lacticaseibacillus rhamnosus against various adverse conditions as compared to WPC. These findings suggest that the studied W/O/W emulsions systems have the potential to deliver probiotics in food substrates to enhance their viability during production processing, storage transportation, and digestion.

Can Lactoferrin, a Natural Mammalian Milk Protein, Assist in the Battle against COVID-19?

Notwithstanding mass vaccination against specific SARS-CoV-2 variants, there is still a demand for complementary nutritional intervention strategies to fight COVID-19. The bovine milk protein lactoferrin (LF) has attracted interest of nutraceutical, food and dairy industries for its numerous properties-ranging from anti-viral and anti-microbial to immunological-making it a potential functional ingredient in a wide variety of food applications to maintain health. Importantly, bovine LF was found to exert anti-viral activities against several types of viruses, including certain SARS-CoV-2 variants. LF's potential effect on COVID-19 patients has seen a rapid increase of in vitro and in vivo studies published, resulting in a model on how LF might play a role during different phases of SARS-CoV-2 infection. Aim of this narrative review is two-fold: (1) to highlight the most relevant findings concerning LF's anti-viral, anti-microbial, iron-binding, immunomodulatory, microbiota-modulatory and intestinal barrier properties that support health of the two most affected organs in COVID-19 patients (lungs and gut), and (2) to explore the possible underlying mechanisms governing its mode of action. Thanks to its potential effects on health, bovine LF can be considered a good candidate for nutritional interventions counteracting SARS-CoV-2 infection and related COVID-19 pathogenesis.

A population-based study on prevalence and predisposing risk factors of infant functional gastrointestinal disorders in a single center in Southern Fujian.

Background and aim: The prevalence of infant functional gastrointestinal disorders (FGIDs) varies across different areas but is largely unknown in southern Fujian. The aim of this study is to evaluate the prevalence of infant FGIDs in southern Fujian according to Rome IV diagnostic criteria. Methods: A cross-sectional prospective questionnaire-based survey was conducted among healthy infants between 0 and 3 months of age in southern Fujian. A total of 1,006 infants who received a physical examination from October 2017 to October 2018 were recruited in this study. Parents or caregivers provided demographic information and completed the questionnaire on gastrointestinal symptoms for infants. Infants with FGIDs were diagnosed using the Rome IV criteria. Results: Based on the Rome IV criteria, the prevalence of having a FGID in infants is 58.3% (586/1,006). The most common FGIDs in infants were regurgitation (45.7%, 460/1,006), followed by difficult defecation (3.6%, 36/1,006), functional constipation (3.2%, 32/1,006), and colic (2.4%, 24/1,006). No infants fulfilled diagnostic criteria for rumination syndrome and cyclic vomiting syndrome. Among the infants with FGIDs, 457 cases (78.0%, 457/586) were found with single FGID. Combined FGIDs were diagnosed in 129 (22.0%, 129/586) infants; of whom, 21.2% (124/586) had double disorders and 0.9% (5/586) had triple disorders. The most common combined FGIDs were regurgitation and difficult defecation (12.8%), followed by regurgitation and colic (2.4%). Risk factor analysis revealed that younger paternal age (B = 0.424, P = 0.004), paternal history of FGIDs (B = 0.821, P = 0.000), maternal history of FGIDs (B = 0.427, P = 0.012), and probiotics received in infant (B = 0.324, P = 0.032) were associated with an increased risk of infant FGIDs, whereas vitamin D supplementation after birth (B = -0.690, P = 0.000) can reduce the risk of developing FGIDs. Conclusion: FGIDs are common in infants living in southern Fujian according to Rome IV diagnostic criteria. The most common FGIDs in infants were regurgitation, difficult defecation, and functional constipation. Factors including younger paternal age, parental history of FGIDs, and the probiotic supplementation in infant showed a significant association with infant FGIDs. Whereas, vitamin D supplementation in infant was found to be a protective factor against FGIDs.

The Pretreatment of Xiaoqinglong Decoction Alleviates Inflammation and Oxidative Damage and Up-Regulates Angiotensin-Converting Enzyme 2 in Lipopolysaccharide-Induced Septic Acute Lung Injury Rats.

Xiaoqinglong decoction (XQLD), a classic prescription of Traditional Chinese Medicine, has already been used clinically to cure acute lung injury (ALI), but its mechanism remains unclear. This subject aimed to explore the preventive role of XQLD in septic ALI rats besides its effects on angiotensin-converting enzyme (ACE)2 and its downstream factors. After, respectively, administrated with different concentrations of XQLD (6.25 g/kg/d, 12.5 g/kg/d, 25 g/kg/d) for 5 days and dexamethasone (DEX, 1 mg/kg) for 0.5 h, the rat models of ALI were established by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) for 24 h. All rats were evaluated by lung function test, arterial blood gas analysis, morphological observation, lung wet/dry (W/D) ratio, and the lung injury score. The levels of malonaldehyde (MDA), superoxide dismutase (SOD), interleukin (IL)-1ß, tumor necrosis factor (TNF)-α, and angiotensin (Ang) (1-7) in the lung were measured through biochemical and ELISA kits. The expressions of angiotensin-converting enzyme (ACE)2, mitochondrial assembly receptor (MasR), and nuclear factor (NF)-κB in lung tissue were detected by qRT-PCR and western blotting. Positive reaction cells of MasR were observed by immunohistochemistry. The results show that XQLD significantly ameliorated septic lung injury including edema and hemorrhage, as well as improved pulmonary function and arterial blood gas. Furthermore, XQLD markedly decreased the levels of IL-1ß, TNF-α, MDA, and NF-κB while increased the levels of SOD, Ang (1-7), ACE2, and MasR in septic ALI rats. Pearson correlation showed that the expressions of ACE2 were inversely related to IL-1ß, TNF-α, MDA, and NF-κB and positively correlated with SOD contents. Our data indicated that XQLD pretreatment alleviated inflammation and oxidative damage in septic ALI rats, which might be related to the up-regulation of ACE2-Ang (1-7)-MasR axis and inhibition of the NF-κB pathway.

[Electroacupuncture preconditioning improves pulmonary function via inhibiting inflammatory response and up-regulating expression of ACE2 and Ang (1-7) in lipopolysaccharide-induced acute lung injury rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli"(ST36) pretreatment on lung functions, inflammatory response, and levels of angiotensin-converting enzyme 2 (ACE2) and angiotensin (1-7) ï¼»Ang (1-7)ï¼½ in rats with sepsis-induced acute lung injury (ALI), so as to explore its mechanisms underlying improvement of ALI. METHODS: Thirty male SD rats were randomly divided into normal, model and EA groups (n=10 in each group). The sepsis-related ALI model was established by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). Rats of the EA group received EA (4 Hz/20 Hz, 1-3 mA) stimulation at bilateral ST36 for 30 min, once each day, for 7 days before modeling. The lung functions including forced vital capacity (FVC), forced expiratory volume at 0.1 second (FEV0.1) and FEV0.3 were detected using a respiratory function detector for small animals at 3 h after modeling. The bronchoalveolar lavage fluid (BALF) was collected for assaying the contents of Ang (1-7), tumor necrosis factor-α (TNF-α) and interleukin-1 ß (IL-1ß) using ELISA. The lung wet/dry weight (W/D) ratio, FEV0.1/FVC, and FEV0.3/FVC were calculated. The histopathological changes of lung tissues were displayed by hematoxylin-eosin (H.E.) staining. The expression of ACE2 and mitochondrial assembly receptor (MasR) mRNAs and proteins in the lung tissue was detected by fluorescence quantitative real-time PCR and Western blot, separately. RESULTS: Following modeling, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and the expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly decreased (P<0.01), while the level of W/D ratio and TNF-α and IL-1ß contents in the BALF significantly increased (P<0.01) in the model group relevant to the normal group. In comparison with the model group, the levels of FVC, FEV0.1, FEV0.3, ratio of FEV0.1/FVC and FEV0.3/FVC, content of Ang (1-7) in the BALF, and expression levels of ACE2 and MasR mRNAs and proteins in the lung tissue were significantly increased (P<0.05, P<0.01), whereas the level of W/D ratio, and TNF-α and IL-1ß contents in the BALF were significantly decreased (P<0.05, P<0.01) in the EA group. H.E. staining showed pulmonary interstitial edema and alveolar septum thickening with severe inflammatory cell infiltration in the model group, which was relatively milder in the EA group. CONCLUSION: EA preconditioning at ST36 can improve pulmonary function in sepsis-related ALI rats, which may be related to its effects in inhibiting inflammatory response and up-regulating ACE2 and MasR expression and Ang (1-7) content in the lung tissue.

[Effects of pre-moxibustion on expression of phosphorylated Tau protein and related protein kinases in hippocampal CA3 region of AD rats].

OBJECTIVE: To observe the effect of pre-moxibustion at "Baihui"(GV20), "Shenshu"(BL23) and "Zusanli"(ST36) on expression of Tau protein and related protein kinases as glycogen synthase kinase-3ß (GSK-3ß), etc. in the hippocampal CA3 region of Alzheimer's disease (AD) rats, so as to explore its mechanism underlying prevention and treatment of AD cognitive impairment. METHODS: Male SD rats were randomly divided into 4 groups: normal control, sham operation， model and pre-moxibustion，with 9 rats in each group. Rats of the pre-moxibustion group received moxibustion of GV20, BL23 and ST36 for 15 min, once a day, 6 days a week for 3 weeks. After completion of moxibustion, the AD model was reproduced by injection of amyloid beta-peptide 25-35(Aß 25-35) aggregation solution 1 µL (5 µg/µL) into the bilateral hippocampus, rats of the sham operation group received injection of the same dose of normal saline into the hippocampus. The spatial learning-memory ability was detected using Morris water maze test, and changes of the ultrastructure of hippocampal neurons were observed using electron microscope, and those of histopathological changes of hippocampus tissue observed using hematoxylin eosin (H.E.) staining. The expression levels of hippocampal GSK-3ß, p-Tau, CDK5 and Synapsin I proteins were detected by Western blot and immunohistochemistry, respectively. RESULTS: No significances were found between the normal control and sham groups in all the indexes (P>0.05). Compared with the control group, the escape latency of place navigation test of Morris water maze test, expression of GSK-3ß and CDK5 and the immunoactivity of GSK-3ß, CDK5 and p-Tau were significantly increased (P<0.01), and the residence time in the platform quadrant and the number of platform crossing of spatial prob test and the expression of Synapsin Ⅰ significantly reduced in the model group (P<0.01). Following the intervention, the increase of escape latency, expression of GSK-3ß and CDK5 and the immunoactivity of GSK-3ß, CDK5 and p-Tau, and the decrease of residence time in the platform quadrant, number of platform crossing and the expression of Synapsin Ⅰ were reversed in the pre-moxibustion group (P<0.05, P<0.01). Outcomes of ultrastructure and histopathological observations respectively showed edema of hippocampal nerve cells at varying degrees, moderate edema of the cytoplasma, chromatin condensation at the edge of the nucleus, partial mitochondrial vacuole-like degeneration, fracture of tubular crest, edema and expansion of Golgi body, disappearance of polarity, fracture of the rough endoplasmic reticulum, degeneration of ribosome and partial myelin axon and reduced synaptic vesicles in the presynaptic capsule; and reduced number of neurons with shrank body, disappearance of nucleolus and blurred nuclear boundary and vacuole-like degeneration in some of them in the model group, which were relatively milder in the pre-moxibustion group. CONCLUSION: Pre-moxibustion at GV20, BL23 and ST36 plays a role in slowing down the occurrence and development of cognitive impairment in AD rats, which may be related to its functions in inhibiting tau protein hyperphosphorylation and reducing the expression of some related protein kinases in the hippocampus.

[Effect of electroacupuncture on pulmonary neuroendocrine cells and secretion of neuroactive substances in lung of COPD rats].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Feishu" (BL13) on the activation and secretion of calcitonin gene-related peptide (CGRP) and 5-hydroxytryptamine (5-HT) of pulmonary neuroendocrine cells (PNECs) and inflammatory response in rats with chronic obstructive pulmonary disease (COPD), so as to explore its underlying mechanisms in treating COPD. METHODS: Male SD rats were randomly divided into normal control, COPD model and EA groups, with 7 rats in each group. The COPD model was established by forced inhale of cigarette smoke for 1 h in a self-made box (1 m×1 m×1 m in volume), twice daily for 12 weeks. EA (4 Hz/20 Hz, 1-3 mA) was applied at bilateral ST36 and BL13 acupoints for 30 min, once a day for 14 consecutive days. The pulmonary function including the forced vital capacity (FVC), forced expiratory volume at 0.1 second (FEV0.1), FEV0.3, FEV0.1/FVC and FEV0.3/FVC was detected using a lung function analyzer for small animals. The lung tissue was sampled for observing histopathological changes by using H.E. staining, for observing expression and distribution of PNECs by Grimelius silver staining, and for detecting the immunoactivity (integrated optical density) of CGRP and 5-HT by using immunohistochemistry. The contents of CGRP, 5-HT, tumor necrosis factor-α (TNF-α), interleukin-1ß (IL-1ß) and transforming growth factor-ß1 (TGF-ß1) in the bronchoalveolar lavage fluid (BALF) and lung tissue were detected by ELISA, and the correlations between TNF-α and CGRP, IL-1ß and CGRP, TNF-α and 5-HT, and IL-1ß and 5-HT levels were analyzed. The mRNA and protein expression levels of nerve fiber markers of CGRP and purinergic receptor P2X ligand gated ion channel 3 (P2X3) which dominate PNECs in the lung tissue were detected by real-time fluorescence quantitative PCR and Western blot, respectively. RESULTS: Compared with the normal control group, the levels of FVC, FEV0.1, FEV0.3, and the ratios of FEV0.1/FVC and FEV0.3/FVC were significantly decreased (P<0.05, P<0.01), while the immunoactivity of PNECs, CGRP and 5-HT, the contents of CGRP, 5-HT, TNF-α, IL-1ß and TGF-ß1 in the BALF and lung tissue, and the expression levels of CGRP and P2X3 mRNAs and proteins in the lung tissue significantly increased in the COPD model group (P<0.01, P<0.05). Following EA intervention, both the increased and decreased levels of all the indexes mentioned above were reversed (P<0.05, P<0.01) except FEV0.3. H.E. staining showed severe deformed bronchial lumen with thickened wall and alveolar septum, and obvious inflammatory cell infiltration and reduced number of alveolar lumen fusion in the COPD model group, which was mild in the EA group. A positive correlation was found between TNF-α and CGRP, IL-1ß and CGRP, TNF-α and 5-HT,IL-1ß and 5-HT levels in both BALF and lung tissues (P<0.01). CONCLUSION: EA at ST36 and BL13 can improve lung function and reduce inflammatory response in COPD rats, which may be related to its function in inhibiting the activation of PNECs and release of neuroactive substances.

The complete chloroplast of Chrysanthemum × morifolium 'Fubaiju'.

Chrysanthemum × morifolium 'Fubaiju,' which is native to Macheng, Hubei, China, has a long cultivation history almost dating back to the early 10th century Song dynasty, and is used as Chrysanthemum tea drink and Chinese traditional medicine. In this study, the complete chloroplast genome sequence of 'Fubaiju' was 151,109 bp, included a large single copy LSC (82,931 bp), a small single copy SSC (18,350 bp), and a pair of inverted repeat regions (24,941 bp). It contained 132 genes with 87 CDS, 8r RNA, and 37 tRNA. The phylogenetic analysis showed that the C. × morifolium 'Fubaiju' was clustered together with C. × morifolium 'Baekma'.

Comprehensive chemical study on different organs of cultivated and wild Sarcandra glabra using ultra-high performance liquid chromatography time-of-flight mass spectrometry (UHPLC-TOF-MS).

To illuminate the similarities and differences between wild and cultivated Sarcandra glabra (S. glabra), we performed a comprehensively study on 26 batches of cultivated S. glabra and 2 batches of wild S. glabra. Chemical constituents and distribution characteristics of roots, stems and leaves in both wild and cultivated S. glabra were investigated through UHPLC-TOF-MS method. The result revealed that there were significant differences between roots, stems and leaves in S. glabra. And the chemical contents in the root part were less or even absence than those in leaf and stem, which suggested the root organ could be excluded as medicine. Meanwhile, the chemical contents of stems and leaves in cultivated S. glabra was sightly higher than that of wild samples. Therefore, cultivated S. glabra may have a high potential for substitution of wild S. glabra without affecting its pharmaceutical properties. In summary, our study could provide important information to the molecular basis for quality control of S. glabra.

[Effect of electroacupuncture on the expression of autophagy related protein in lung tissue of rats with chronic obstructive pulmonary disease].

OBJECTIVE: To observe the effect of electroacupuncture (EA) at "Zusanli" (ST36) and "Feishu" (BL13) on the expression of autophagy related proteins in the lung tissue of rats with chronic obstructive pulmonary disease (COPD), so as to explore the mechanism of EA underlying improvement of COPD. METHODS: Thirty male SD rats were randomly divided into normal, model and EA groups (n=10 in each group). The COPD model was established by intratracheal infusion of Lipopolysaccharide (LPS, 1 mg/kg) and exposure in cigarette smoke. EA was applied to bilateral ST36 and BL13 for 30 min, once every other day for 2 weeks. The pulmonary function (forced vital capacity ï¼»FVCï¼½, forced expiratory volume in 0.1 s and 0.3 s ï¼»FEV0.1, FEV0.3ï¼½, FEV0.1/FVC and FEV0.3/FVC) was detected by animal pulmonary function analysis system. Histopathological changes of the airway and lung were displayed by H.E. staining. Autophagosomes in the airway and lung tissues were observed by electron microscope. The expression of AMP activated protein kinase (AMPK), mammalian target of rapamycin (mTOR), Unc-51 like autophagy activating kinase 1(ULK1), autophagy related protein ATG6(Beclin1)mRNAs in lung tissue were examined by quantitative real-time PCR. The expression of AMPK, mTOR, ULK1, Beclin1 and microtubule-associated protein 1 light chain 3 (LC3)proteins in lung tissue were examined by Western blot. The contents of tumor necrosis factor α (TNF-α) and interleukin 6 (IL-6) in the broncho alveolar lavage fluid (BALF) were assayed by ELISA. RESULTS: Following modeling, the FVC, FEV0.1, FEV0.3, FEV0.1/FVC and FEV0.3/FVC levels were significantly decreased (P<0.01), the infiltration of inflammatory cells and the increase of autophagosomes were obvious in airway and lung tissue, the mRNA and protein expression of AMPK, ULK1, Beclin1 and the ratio of LC3Ⅱ/LC3Ⅰ were increased (P<0.01), while the mRNA and protein expression of mTOR were decreased (P<0.01), the contents of TNF-α and IL-6 in the BALF were increased in the model group compared with the normal group (P<0.01). After EA intervention, all the indexes mentioned above were completely reversed in the EA group relevant to the model group (P<0.01, P<0.05). CONCLUSION: EA at ST36 and BL13 can improve the lung function of COPD rats, which may be related to its effects in inhibiting the autophagy level and reducing the inflammation response in the lung.

Similarity and Specificity of Traditional Chinese Medicine Formulas for Management of Coronavirus Disease 2019 and Rheumatoid Arthritis.

The pathogenesis similarity is leading to the introduction of drugs commonly used in rheumatoid arthritis (RA) into coronavirus disease (COVID-19) treatment. Traditional Chinese medicine (TCM) was widely used for the treatment of infectious diseases and rheumatic diseases. However, there is little knowledge of the relationship between COVID-19 and RA treatment employing TCM formulas. The present work was aimed to compare the similarity and specificity of TCM formulas for the management of COVID-19 and RA, as well as to deduce the potential mechanism of TCM for COVID-19 treatment. Two formulas including lianhuaqingwen (LHQW) and duhuojisheng (DHJS) were selected as the representatives of TCM for COVID-19 and RA treatment, respectively. An integrated network pharmacology was used to investigate their similarity and specificity. Although different herbs are present in the two formulas, they generated fairly similar ingredients, targets, interaction networks and enriched pathways, which were mainly involved in virus infection, inflammation, and immune dysregulation. Undoubtedly, they also exhibited their respective specificity. LHQW showed the cold property and lung channel tropism which dominated heat-clearing and lung-freeing, while DHJS showed the warm property and liver channel tropism. Herbal compatibility of LHQW was more in line with the rules of the TCM formula against coronavirus disease. Although both formulas suggested multifunctionality in virus infection and inflammation, LHQW was inclined to cope with virus infection, while DHJS was inclined to cope with inflammation. Therefore, LHQW was reliable for providing the desired efficacy in COVID-19 management because of its cold property, lung channel tropism, and multifunctionality for coping with virus infection and inflammation.

Total alkaloids from Alstonia scholaris inhibit influenza a virus replication and lung immunopathology by regulating the innate immune response.

BACKGROUND: Alstonia scholaris is a folk medicine used to treat cough, asthma and chronic obstructive pulmonary disease in China. Total alkaloids (TA) from A. scholaris exhibit anti-inflammatory properties in acute respiratory disease, which suggests their possible anti-inflammatory effect on influenza virus infection. PURPOSE: To assess the clinical use of TA by demonstrating their anti-influenza and anti-inflammatory effects and the possible mechanism underlying the effect of TA on influenza A virus (IAV) infection in vitro and to reveal the inhibitory effect of TA on lung immunopathology caused by IAV infection. METHODS: Antiviral and anti-inflammatory activities were assessed in Madin-Darby canine kidney (MDCK) and A549 cells and U937-derived macrophages infected with influenza A/PR/8/34 (H1N1) virus. Proinflammatory cytokine levels were measured by real-time quantitative PCR and Bio-Plex assays. The activation of innate immune signaling induced by H1N1 virus in the absence or presence of TA was detected in A549 cells by Western blot. Furthermore, mice were infected intranasally with H1N1 virus and treated with TA (50, 25 and 12.5 mg/kg/d) or oseltamivir (60 mg/kg/d) for 5 days in vivo. The survival rates and body weight were recorded, and the viral titer, proinflammatory cytokine levels, innate immune cell populations and histopathological changes in the lungs were analyzed. RESULTS: TA significantly inhibited viral replication in A549 cells and U937-derived macrophages and markedly reduced cytokine and chemokine production at the mRNA and protein levels. Furthermore, TA blocked the activation of pattern recognition receptor (PRR)- and IFN-activated signal transduction in A549 cells. Critically, TA also increased the survival rate, reduced the viral titer, suppressed proinflammatory cytokine production and innate immune cell infiltration and improved lung histopathology in a lethal PR8 mouse model. CONCLUSION: TA exhibits anti-viral and anti-inflammatory effects against IAV infection by interfering with PRR- and IFN-activated signal transduction.

Phytotherapy using blueberry leaf polyphenols to alleviate non-alcoholic fatty liver disease through improving mitochondrial function and oxidative defense.

BACKGROUND: Since non-alcoholic fatty liver disease (NAFLD) pathogenesis is multi-factorial, pharmacotherapy with a specific target commonly exhibits limited efficacy. Phytotherapy, whose therapeutic efficacy is based on the combined action of several active compounds, offers new treatment opportunity for NAFLD. As a representative, many natural polyphenols could be utilized in phytotherapy for NAFLD. PURPOSE: In present work, we aimed to investigate the therapeutic effects and underlying mechanism of polyphenols in blueberry leaves (PBL) on NAFLD from a mitochondria-centric perspective since mitochondrial dysfunction could play a dominant role in NAFLD. METHODS: Identification and quantification of PBL were performed using liquid chromatography coupled with tandem mass spectrometry. The beneficial effects, especially improving mitochondrial function, and potential mechanism of PBL on NAFLD were studied by in vitro and in vivo study. RESULTS: Polyphenols were abundant in blueberry leaves making it advantaged in NAFLD phytotherapy. PBL effectively alleviated hepatic steatosis, oxidative stress and inflammation as indicated by both in vitro and in vivo study. Furthermore, PBL mediated improvement of mitochondrial dysfunction and antioxidant capability through activation of AMPK/PGC-1α/SIRT3 signaling axis. CONCLUSION: Considering that mitochondrial dysfunction takes precedence over hepatic steatosis and induces NAFLD development, we conclude that PBL improve mitochondrial dysfunction and oxidative defense, subsequently alleviate hepatic steatosis, oxidative stress and inflammation, and eventually alleviate NAFLD.

Study on the anti-tumor mechanism related to immune microenvironment of Bombyx Batryticatus on viral and non-viral infections of hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a malignant primary liver cancer with poor prognosis. Most previous studies on anti-HCC effects of traditional Chinese medicines (TCM) have focused on the mechanism of direct action and few researchers considered that TCM can inhibit tumor progression and improve prognosis of HCC patients through regulating tumor microenvironment (TME). In this study, network pharmacology combined bioinformatics methods were employed to analysis mechanism of Bombyx batryticatus (B. batryticatus, one of the most frequently used traditional Chinese animal medicines, has been used in some Asian countries for centuries as an anticancer agent, anti-inflammatory agent, and antioxidant.) in regulating TME of HCC. The results showed that 24 core targets and 2 compounds were identified from overlapping between differential expression genes related to HCC in the cancer genome atlas (TCGA) database and targets of B. batryticatus in TCMSP database. For further analyzing the role of TME heterogeneity of HCC on anti-HCC mechanism of B. batryticatus, the correlation of core targets related with overall survival of HCC with TME cells in hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (VIR) and non-hepatitis C or hepatitis B virus-associated hepatocellular carcinoma (NVIR) were calculated, respectively. The results showed that AKR1C3, SPP1 were significantly related with macrophages in VIR and other targets including NR1I2, CYP1A2 and CYP3A4 were significantly associated with macrophages in NVIR; the target protein AKR1C3 was significantly negative correlated with macrophages M1 in VIR (cor=-0.35, P-value<0.001) and the correlation between AKR1C3 and macrophages M1 was poor in NVIR group (cor = 0.064, P-value = 0.36). Additionally, survival curve of AKR1C3 showed that poor prognosis in VIR group can be related to high level of AKR1C3 (HR = 2.32, 95 % CI: 1.18-4.56, P-value = 0.012), and no signified gene can be found in NVIR group (P-value>0.05). In conclusion, the molecular mechanism of anti-HCC of B. batryticatus can be related to the tumor microenvironment to some extent. B. batryticatus may exert its anti-cancer effects and improve prognosis of patients by regulating macrophages M1 in VIR and NVIR through acting on different targets.

Investigation into perturbed nucleoside metabolism and cell cycle for elucidating the cytotoxicity effect of resveratrol on human lung adenocarcinoma epithelial cells.

In an effort to understand the molecular events contributing to the cytotoxicity activity of resveratrol (RSV), we investigated its effects on human lung adenocarcinoma epithelial cell line A549 at different concentrations. Cellular nucleoside metabolic profiling was determined by an established liquid chromatography-mass spectrometry method in A549 cells. RSV resulted in significant decreases and imbalances of deoxyribonucleoside triphosphates (dNTPs) pools suppressing subsequent DNA synthesis. Meanwhile, RSV at high concentration caused significant cell cycle arrest at S phase, in which cells required the highest dNTPs supply than other phases for DNA replication. The inhibition of DNA synthesis thus blocked subsequent progression through S phase in A549 cells, which may partly contribute to the cytotoxicity effect of RSV. However, hydroxyurea (HU), an inhibitor of RNR activity, caused similar dNTPs perturbation but no S phase arrest, finally no cytotoxicity effect. Therefore, we believed that the dual effect of high concentration RSV, including S phase arrest and DNA synthesis inhibition, was required for its cytotoxicity effect on A549 cells. In summary, our results provided important clues to the molecular basis for the anticancer effect of RSV on epithelial cells.

Defense of pyrethrum flowers: repelling herbivores and recruiting carnivores by producing aphid alarm pheromone.

(E)-ß-Farnesene (EßF) is the predominant constituent of the alarm pheromone of most aphid pest species. Moreover, natural enemies of aphids use EßF to locate their aphid prey. Some plant species emit EßF, potentially as a defense against aphids, but field demonstrations are lacking. Here, we present field and laboratory studies of flower defense showing that ladybird beetles are predominantly attracted to young stage-2 pyrethrum flowers that emitted the highest and purest levels of EßF. By contrast, aphids were repelled by EßF emitted by S2 pyrethrum flowers. Although peach aphids can adapt to pyrethrum plants in the laboratory, aphids were not recorded in the field. Pyrethrum's (E)-ß-farnesene synthase (EbFS) gene is strongly expressed in inner cortex tissue surrounding the vascular system of the aphid-preferred flower receptacle and peduncle, leading to elongated cells filled with EßF. Aphids that probe these tissues during settlement encounter and ingest plant EßF, as evidenced by the release in honeydew. These EßF concentrations in honeydew induce aphid alarm responses, suggesting an extra layer of this defense. Collectively, our data elucidate a defensive mimicry in pyrethrum flowers: the developmentally regulated and tissue-specific EßF accumulation and emission both prevents attack by aphids and recruits aphid predators as bodyguards.

Molecularly Imprinted Photo-electrochemical Sensor for Human Epididymis Protein 4 Based on Polymerized Ionic Liquid Hydrogel and Gold Nanoparticle/ZnCdHgSe Quantum Dots Composite Film.

A novel ionic liquid, 3-{[{4-[((carbamoyl)amino)ethyl methacrylate]butyl} ((carbamoyl)amino)ethyl methacrylate]propyl}-1-ethenyl-1H-imidazol-3-ium bromide (CCPEimBr) functionalized with vinyl, amino, and methacrylate groups, was synthesized and characterized with 1H NMR, FTIR, and HPLC-MS techniques. CCPEimBr was adopted as the functional monomer to prepare a molecularly imprinted polymerized ionic liquid hydrogel film on a glassy carbon electrode surface for human epididymis protein 4 (HE4) sensing. Gold nanoparticles (AuNPs) and ZnCdHgSe QDs were incorporated into the imprinted film as photo-electric active materials. The photocurrent response was measured to investigate the sensing performance of the imprinted sensors toward HE4. The imprinted photo-electrochemical sensor shows excellent selectivity, sensitivity, stability, and accuracy for HE4 determination. Experimental conditions including incubation time and pH value for determining HE4 were optimized in this study. The photocurrent variation (ΔI) decreased with increasing HE4 concentration (cHE4), and it was linearly proportional to cHE4 varied from 25 pg mL-1 to 4.0 ng mL-1. The detection limit of the imprinted sensor for determining HE4 was estimated to be 15.4 pg mL-1 (S/N = 3). The imprinted photo-electrochemical sensor was used to determine HE4 in human serum samples accurately.

Quantitation of camellianin A in HepG2 cells using a high performance liquid chromatography-electrospray ionization tandem mass spectrometric method.

The present study was designed to develop a sensitive and selective high performance liquid chromatography-tandem mass spectrometric method for the determination of Camellianin A in HepG2 cells. The extraction of Camellianin A was achieved using 15% trichloroacetic acid and then separated on a C18 column interfaced with a triple quadrupole tandem mass spectrometer in multiple reaction monitoring mode. The mobile phase was consisted of methanol-water (0.1% formic acid) (55 : 45, V/V). The total run time was 5.0 min. The method was linear in the concentration range of 0.25-250.0 ng·mL-1. The lower limit of quantification was 0.25 ng·mL-1. The intra- and inter-day relative standard deviations of entire concentration range were less than 9.3%. The proposed HPLC-MS/MS method was successfully applied to detect the intracellular concentration of Camellianin A in HepG2 cells.