"Plant Golden" C. sativus: Qualitative and quantitative analysis of major components in stigmas and petals and their biological activity in vitro.

Crocus sativus L. (C. sativus) has its stigma as the main valuable part used. With extremely low production and high prices, stigma is considered a scarce resource. As a result, its petals, considered as by-products, are often discarded, leading to significant waste. We developed a UPLC-Q-Orbitrap HRMS method for qualitative analysis of stigmas and petals and a UHPLC-QQQ-MS/MS method for simultaneous quantification of 9 characteristic active compounds for the first time, and compared their biological activity in vitro. The results indicated that a total of 63 compounds were identified in the petals and stigmas. The content of flavonoids in the petals was significantly superior to that in the stigma, and the content of quercetin in the petals was 50 times higher than that in the stigma. The results of the in vitro evaluation of biological activity indicated that both the petals （•OH: IC50=39.70 mg/mL; DPPH: IC50=28.37 mg/mL; ABTS: IC50=0.9868 mg/mL）and stigma （•OH: IC50=34.41 mg/mL; DPPH: IC50=38.99 mg/mL; ABTS: IC50=3.194 mg/mL）demonstrated comparable antioxidant activities. However, the tyrosinase inhibitory activity in petals （IC50=21.17 mg/mL） was weaker than that in stigma（IC50=1.488 mg/mL）. This study provides a fast, reliable, and efficient analytical method that can be used for the quality assessment of petals as a natural resource and its related products in the food and pharmaceutical industries.

Analysis of the pharmacodynamic difference between Xiaojin Pills taken with Chinese Baijiu and water based on serum pharmacochemistry and pharmacokinetics.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills (XJPs), which has the function of dissipating knots and dispersing swelling, removing blood stasis, and relieving pain, is a classic prescription for the treatment of mammary glands hyperplasia. It is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinics. Previous studies have shown that the efficacy of XJPs "taken orally after soaked with Chinese Baijiu" in tradition was significantly better than that of taking it orally with water in modern in terms of activating the blood, anti-inflammation, analgesia, anti-mammary gland hyperplasia, anti-breast cancer and its metastasis in vitro and in vivo, especially under low-dose conditions. However, the material basis for the difference in efficacy between XJP&B and XJP&W is still unclear. AIM OF THE STUDY: To analyze the material basis of the significant difference in efficacy between XJP&B and XJP&W from the perspective of serum pharmacochemistry and pharmacokinetics, and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu". MATERIALS AND METHODS: Ultra-high performance liquid chromatography-mass spectrometry combined with a multivariate statistical analysis method were used to screen the differential components in the Chinese Baijiu extract and the water extract of XJPs and the corresponding residues, so as to clarify the differential components between XJP&B and XJP&W in vitro. The migrating components in the blood after XJP&B and XJP&W were characterized by serum pharmacochemical methods, in order to clarify the differential components in rats. The pharmacokinetic parameters of the representative components absorbed into the blood were compared between XJP&B and XJP&W by the pharmacokinetics study method, in order to determine the dynamic changes of the representative components in rats. RESULTS: The identification results of different components in vitro showed that there were 34 and 12 different compounds between the Chinese Baijiu extract and water extract of XJPs, and the residues after Chinese Baijiu extraction and water extraction, respectively. The content of different components such as arachidonic acid, ursolic acid, 3-acetyl-11-keto-ß-boswellic acid, 2α-hydroxyursolic acid, and oleanolic acid was higher in the Chinese Baijiu extract, which was more than twice the content in the water extract. The results of the serum pharmacochemistry study indicated that 42 prototype components were identified in the serum of rats after XJP&B and XJP&W, including organic acids, alkaloids, steroids, and terpenoids. And XJP&B increased the absorption of the prototype components of organic acids in XJPs into the blood. The pharmacokinetic study results of representative components demonstrated that the mean plasma concentration-time profile and pharmacokinetic parameters of muscone, aconitine, and 3-acetyl-11-keto-ß-boswellic acid were significantly different between XJP&B and XJP&W. Compared with XJP&W, the Cmax and AUC0-t of muscone and aconitine in XJP&B were higher, and the T1/2 and MRT0-t of 3-acetyl-11-keto-ß-boswellic acid in XJP&B were relatively longer. CONCLUSION: This research proved that "taking XJPs orally after being soaked with Chinese Baijiu" can increase the dissolution and absorption of active ingredients in XJPs, increase the plasma concentration and content of representative ingredients, and prolong its action time, thus enhancing the biological activity of XJPs in vitro and in vivo. To a certain extent, this study revealed the material basis of the significantly better efficacy of XJP&B than XJP&W and clarified the scientific connotation of XJPs "taken orally after soaked with Chinese Baijiu", which can provide a theoretical basis for the optimization of XJPs' clinical administration method.

Interactions between Gut Microbiota and Polyphenols: New Insights into the Treatment of Fatigue.

Fatigue seriously affects people's work efficiency and quality of life and has become a common health problem in modern societies around the world. The pathophysiology of fatigue is complex and not fully clear. To some degree, interactions between gut microbiota and host may be the cause of fatigue progression. Polyphenols such as tannin, tea polyphenols, curcumin, and soybean isoflavones relieve fatigue significantly. Studies have shown that the gut microbiota is able to convert these active compounds into more active metabolites through intestinal fermentation. However, the mechanism of anti-fatigue polyphenols is currently mainly analyzed from the perspective of antioxidant and anti-inflammatory effects, and changes in gut microbiota are rarely considered. This review focuses on gut microecology and systematically summarizes the latest theoretical and research findings on the interaction of gut microbiota, fatigue, and polyphenols. First, we outline the relationship between gut microbiota and fatigue, including changes in the gut microbiota during fatigue and how they interact with the host. Next, we describe the interactions between the gut microbiota and polyphenols in fatigue treatment (regulation of the gut microbiota by polyphenols and metabolism of polyphenols by the gut microbiota), and how the importance of potential active metabolites (such as urolithin) produced by the decomposition of polyphenols by gut microbiota is emerging. Based on the new perspective of gut microbiota, this review provides interesting insights into the mechanism of polyphenols in fatigue treatment and clarifies the potential of polyphenols as targets for anti-fatigue product development, aiming to provide a useful basis for further research and design.

A 2-oxoglutarate-dependent dioxygenase converts dihydrofuran to furan in Salvia diterpenoids.

Tanshinone ⅡA (TⅡA), a diterpene quinone with a furan ring, is a bioactive compound found in the medicinal herb redroot sage (Salvia miltiorrhiza Bunge), in which both furan and dihydrofuran analogs are present in abundance. Progress has been made recently in elucidating the tanshinone biosynthetic pathway, including heterocyclization of the dihydrofuran D-ring by cytochrome P450s; however, dehydrogenation of dihydrofuran to furan, a key step of furan ring formation, remains uncharacterized. Here, by differential transcriptome mining, we identified six 2-oxoglutarate-dependent dioxygenase (2-ODD) genes whose expressions corresponded to tanshinone biosynthesis. We showed that Sm2-ODD14 acts as a dehydrogenase catalyzing the furan ring aromatization. In vitro Sm2-ODD14 converted cryptotanshinone to TⅡA and thus was designated TⅡA synthase (SmTⅡAS). Furthermore, SmTⅡAS showed a strict substrate specificity, and repression of SmTⅡAS expression in hairy root by RNAi led to increased accumulation of total dihydrofuran-tanshinones and decreased production of furan-tanshinones. We conclude that SmTⅡAS controls the metabolite flux from dihydrofuran- to furan-tanshinones, which influences medicinal properties of S. miltiorrhiza.

Engineering high coenzyme Q10 tomato.

Coenzyme Q (CoQ) is vital for energy metabolism in living organisms. In humans, CoQ10 deficiency causes diseases and must be replenished via diet; however, CoQ content in plant foods is primarily low. Here, we report the breeding of high CoQ10 tomato lines by expressing four enzymes with a fruit-specific promoter, which modifies the chloroplast chorismate pathway, enhances cytosolic isoprenoid biosynthesis, and up-regulates the first two reactions in mitochondrion that construct the CoQ10 polyisoprenoid tail. We show that, while the level of the aromatic precursor could be markedly elevated, head group prenylation is the key to increasing the final CoQ10 yield. In the HUCD lines expressing all four transgenes, the highest CoQ10 content (0.15 mg/g dry weight) shows a seven-fold increase from the wild-type level and reaches an extraordinarily rich CoQ10 food grade. Overviewing the changes in other terpenoids by transcriptome and metabolic analyses reveals variable contents of carotenoids and α-tocopherol in the HUCD lines. In addition to the enigmatic relations among different terpenoid pathways, high CoQ10 plants maintaining substantial levels of either vitamin can be selected. Our investigation paves the way for the development of CoQ10-enriched crops as dietary supplements.

Comparative study on the pharmacodynamic difference of oral administration of Xiaojin Pills accompanied with Chinese Baijiu and water.

ETHNOPHARMACOLOGICAL RELEVANCE: Xiaojin Pills is a classic prescription for the treatment of mammary glands hyperplasia with a history of nearly 300 years, and is also the first choice of Chinese patent medicine for the clinical treatment of mammary glands hyperplasia in contemporary traditional Chinese medicine clinic. Clinical and animal studies have shown that Xiaojin Pills has the effects of anti-mammary glands hyperplasia, promoting blood circulation, anti-inflammation and analgesia. However, its initial administration method was "taking orally after soaked with Chinese Baijiu", the modern method was changed to "taking orally with water" in recent 20 years. Whether there is any difference in the efficacy of the two administration methods is still unknown. AIM OF THE STUDY: To reveal the difference in efficacy and metabolic mechanism of anti-mammary gland hyperplasia between the oral administration of Xiaojin Pills accompanied with Chinese Baijiu (XJP&B) and water (XJP&W). MATERIALS AND METHODS: COX-2 inhibition rate test and anti-platelet aggregation activity test were used to investigate the efficacy difference between the 40 vol% Chinese Baijiu and water extracts of Xiaojin Pills on anti-inflammatory and blood-activating in vitro. Kunming male mice (20 ± 5 g) and SD female rats (200-220 g) were orally treated with XJP&B and XJP&W, respectively. Then the difference in anti-inflammatory and analgesic effects between XJP&B and XJP&W were evaluated via xylene-induced ear swelling test, formaldehyde-induced pain test, and acetic acid-induced writhing test in mice. Determination of nipple diameter, pathological examination of mammary gland tissue, determination of serum E2, P and FSH content and hemorheological parameters of rats with mammary gland hyperplasia were performed to explore the efficacy difference in anti-mammary gland hyperplasia between XJP&B and XJP&W. Metabolomics was used to study the difference of anti-mammary gland hyperplasia mechanism between XJP&B and XJP&W. RESULTS: The results showed that the effect of XJP&B was superior to that of XJP&W in anti-platelet aggregation, inhibition of inflammation and pain, and anti-mammary gland hyperplasia. Interestingly, the advantages were more significant under low-dose condition. In addition, the mechanism of the two combinations against mammary gland hyperplasia was indeed different. Their common metabolic pathways include tryptophan metabolism and alanine, aspartic acid and glutamic acid metabolism. However, Chinese Baijiu and XJP&B also have additional regulatory effects on linoleic acid metabolic pathway. CONCLUSION: In brief, this research demonstrated that the efficacy of XJP&B was better than that of XJP&W in activating the blood, anti-inflammation, analgesia and anti-mammary gland hyperplasia, which means that XJP&B has synergistic and superior effects. The special dose-effect relationship under the condition of XJP&B was also found, laying the foundation for clinical treatment to reduce the dosage and shorten the medication cycle, which is beneficial to reduce the economic burden of patients.

High or low temperature extraction, which is more conducive to Triphala against chronic pharyngitis?

OBJECTIVE: Explore the effects of high-temperature reflux extraction and low-temperature decompressing inner ebullition on Triphala's chemical composition and anti-chronic pharyngitis activity. METHODS: The network pharmacology was used to analyze the material basis, targets and pathways of Triphala for chronic pharyngitis. HPLC were used to compare the fingerprint profile and content of components between the two extracts. The antioxidant and anti-chronic pharyngitis activities of the two extracts were compared by DPPH assay and ammonia induced chronic pharyngitis model in rats. RESULTS: The network pharmacology results showed that the active ingredients of Triphala for chronic pharyngitis are epigallocatechin-3-gallate, (+)-catechin, epicatechin, epicatechin gallate, (+)-gallocatechin, quercetin, luteolin, leucodelphinidin and other flavonoids; phenolic acids such as gallic acid and ellagic acid; alkaloids such as ellipticine, cheilanthifoline; hydrolyzed tannins such as corilagin and chebulic acid. The high-temperature reflux extract and the low-temperature decompressing inner ebullition extract have extremely significant differences in the fingerprint profile. Among them, the content of gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin, quercetin, and epicatechin gallate in the reflux extract is 1.1-5.3 times as much as decompressing inner ebullition extract. The free radical scavenging ability of reflux extract is significantly stronger than that of decompression extract (p < 0.01), and it has a repairing effect on pharyngeal mucosal damage (reducing keratinization or hyperplasia of mucosal epithelium, reducing inflammatory cell infiltration and bleeding), and reducing IL-1ß (P＜0.05), IL-6 (p＜0.05), TNF-α overexpression ability is stronger than the decompressing inner ebullition extract. CONCLUSIONS: gallic acid, ellagic acid, chebulic acid, catechin, epicatechin, corilagin and epicatechin gallate are the basic aglycones or oligomers of tannin. High temperature reflux extraction can significantly promote the occurrence of the hydrolysis of tannins and significantly increases the content of these components.Therefore, its anti-chronic pharyngitis activity is enhanced. It is suggested that high temperature reflux extraction should be used in the treatment of chronic pharyngitis.

New progress in the pharmacology of protocatechuic acid: A compound ingested in daily foods and herbs frequently and heavily.

Protocatechuic acid is a natural phenolic acid, which widely exists in our daily diet and herbs. It is also one of the main metabolites of complex polyphenols, such as anthocyanins and proanthocyanins. In recent years, a large number of studies on the pharmacological activities of protocatechuic acid have emerged. Protocatechuic acid has a wide range of pharmacological activities including antioxidant, anti-inflammatory, neuroprotective, antibacterial, antiviral, anticancer, antiosteoporotic, analgesia, antiaging activties; protection from metabolic syndrome; and preservation of liver, kidneys, and reproductive functions. Pharmacokinetic studies showed that the absorption and elimination rate of protocatechuic acid are faster, with glucuronidation and sulfation being the major metabolic pathways. However, protocatechuic acid displays a dual-directional regulatory effect on some pharmacological activities. When the concentration is very high, it can inhibit cell proliferation and reduce survival rate. This review aims to comprehensively summarize the pharmacology, pharmacokinetics, and toxicity of protocatechuic acid with emphasis on its pharmacological activities discovered in recent 5 years, so as to provide more up-to-date and thorough information for the preclinical and clinical research of protocatechuic acid in the future. Moreover, it is hoped that the clinical application of protocatechuic acid can be broadened, giving full play to its characteristics of rich sources, low toxicity and wide pharmacological activites.

Effects of inulin supplementation on intestinal barrier function and immunity in specific pathogen-free chickens with Salmonella infection.

We investigated the effects of inulin on intestinal barrier function and mucosal immunity in Salmonella enterica serovar Enteritidis (SE)-infected specific pathogen-free (SPF) chickens. SPF chickens (n = 240, 1-d-old) were divided into 4 groups (6 replicates per group, 10 chickens per replicate): a control group (CON) fed a basal diet without inulin supplementation and 3 SE-infected groups fed a basal diet supplemented with inulin 0% (SE group), 0.5% (0.5% InSE group), and 1% (1% InSE group), respectively. At 28 d of age, the chickens in SE-infected groups were orally infected with SE and in CON group were administrated with phosphated-buffered saline (PBS). Intestinal morphology, mucosal immunity, and intestinal barrier function-related gene expression were analyzed at 1- and 3-d post-infection (dpi). SE challenge significantly increased the mucosal gene expression, such as interleukin-1ß (IL-1ß), lipopolysaccharide-induced tumor necrosis factor factor (LITAF), interferon-γ (IFN-γ), and interleukin-6 (IL-6), and increased serum IFN-γ, secretory IgA (sIgA), and IgG concentration, and significantly decreased the gene expression levels of mucin 2 (MUC2) and claudin-1 at 3 dpi compared with the CON group (P < 0.05). Inulin supplementation improved the expression levels of these immunity- and intestinal barrier function-related genes, increased villus height (VH), and decreased crypt depth (CD) in the duodenum, jejunum, and ileum at 1 and 3 dpi within the SE-challenged groups (P < 0.05). SE challenge significantly increased ileal Toll-like receptor 4 (TLR4) mRNA at 1 and 3 dpi, suppressor of cytokine signaling 3 (SOCS3) mRNA at 1 dpi, and phospho-signal transducer and activator of transcription 3 (p-STAT3) and Janus kinase1 (JAK1) protein expression at 3 dpi compared with the CON group (P < 0.05). Inulin supplementation suppressed p-STAT3 and JAK1 protein expression and promoted ileal TLR4 and SOCS3 mRNA expression at 3 dpi compared with SE group (P < 0.05). In conclusion, inulin alleviated SE-induced gut injury by decreasing the proinflammatory response and enhancing mucosal immunity in chickens.

Dietary Inulin Supplementation Modulates Short-Chain Fatty Acid Levels and Cecum Microbiota Composition and Function in Chickens Infected With Salmonella.

The current study investigated the effects of inulin on the gut microbiota, microbiome functions, and short-chain fatty acids (SCFAs) levels in specific pathogen-free (SPF) chickens infected with Salmonella enteritidis (SE). SPF Arbor Acres chickens (n = 240, 1-day-old) were divided into four groups: a control group (CON) fed a basal diet without inulin supplementation or SE infection, and three groups fed a basal diet supplemented with inulin 0, 0.5, and 1% (SE, 0.5%InSE, 1%InSE, respectively) up to 28-days-old, followed by SE challenge at 28 days of age. Cecal SCFA contents and microbiome composition and function were analyzed at 1-day post-infection. The results showed that SE infection significantly decreased cecal butyrate concentrations compared with the CON group (p < 0.05), while inulin supplementation reversed these changes compared with the SE group (p < 0.05). Inulin supplementation at 1% significantly increased the abundances of Lactobacillus and Streptococcus, and significantly decreased the abundances of Subdoligranulum and Sellimonas compared with the SE group (p < 0.05). The functional profiles of microbial communities based on metagenomic sequencing analysis showed that SE infection significantly increased the abundances of pathways related to carbohydrate metabolism, amino acid metabolism, energy metabolism, metabolism of cofactors and vitamins, and glycan biosynthesis and metabolism (p < 0.05), and significantly decreased the abundances of pathways related to nucleotide metabolism, translation, and replication and repair compared with the CON group (p < 0.05), and these effects were reversed by inulin supplementation (0.5 and 1%) (p < 0.05). In conclusion, inulin modulated the dysbiosis induced by SE infection via affecting SCFA metabolism and microbial functional profiles.

IR780-loaded folate-targeted nanoparticles for near-infrared fluorescence image-guided surgery and photothermal therapy in ovarian cancer.

Background and purpose: Surgery is regarded as the gold standard for patients with advanced ovarian cancer. However, complete surgical removal of tumors remains extremely challenging; fewer than 40% of patients are cured. Here, we developed a new modality of theranostics for ovarian cancer based on a near-infrared light-triggered nanoparticle. Methods: Nanoparticles loading IR780 iodide on base of folate modified liposomes were prepared and used for theranostics of ovarian cancer. Tumor targeting of FA-IR780-NP was evaluated in vitro and in an ovarian xenograft tumor model. A fluorescence stereomicroscope was applied to evaluate the tumor recognition of FA-IR780-NP during surgery. FA-IR780-NP mediated photothermal therapy effect was compared with other treatments in vivo. Results: FA-IR780-NP was demonstrated to specifically accumulate in tumors. IR780 iodide selectively accumulated in tumors; the enhanced permeability and retention effect of the nanoparticles and the active targeting of folate contributed to the excellent tumor targeting of FA-IR780-NP. With the aid of tumor targeting, FA-IR780-NP could be used as an indicator for the real-time delineation of tumor margins during surgery. Furthermore, photothermal therapy mediated by FA-IR780-NP effectively eradicated ovarian cancer tumors compared with other groups. Conclusion: In this study, we present a potential, effective approach for ovarian cancer treatment through near-infrared fluorescence image-guided resection and photothermal therapy to eliminate malignant tissue.

NIR-responsive nanoplatform for pre/intraoperative image-guided carcinoma surgery and photothermal ablation of residual tumor tissue.

Local recurrence is common among patients with advanced cancer who have undergone surgery. Here, we developed a new surgical treatment for cancer based on a nanoparticle that loaded a near-infrared dye (IR780 iodide) and perfluorooctyl bromide into liposomes (NP-IR780). In an orthotopic breast cancer mouse model, NP-IR780 was demonstrated to have excellent tumor-targeting ability due to the selective tumor accumulation of IR780 iodide and the enhanced permeation and retention effect of the nanoparticle. With the excellent targeting ability, concurrent computed tomography and photoacoustic imaging were achieved for preoperative planning. In particular, NP-IR780 could serve as a tumor indicator for near-infrared fluorescence image-guided precise resection of lesions during surgery. Importantly, residual tumors could be ablated through intraoperative photothermal therapy without obvious recurrence. This work provides a theranostic strategy that significantly improved the survival of mice through pre/intraoperative image-guided tumor resection and subsequent photothermal therapy of residual lesions.

Photothermal therapy mediated by phase-transformation nanoparticles facilitates delivery of anti-PD1 antibody and synergizes with antitumor immunotherapy for melanoma.

Melanoma remains one of the most challenging malignant tumor related deaths worldwide and alternative approaches to efficiently treat melanoma are eagerly needed. Anti-PD1 antibody (aPD1) immunotherapy is the most significant and impactful therapy for melanoma by immune checkpoint inhibition and T cell stimulation to mediate tumor killing. But the clinical remission rate of aPD1 immunotherapy is limited in melanoma. Here we show a potent combination of aPD1 and photothermal therapy (PTT) by effective delivery of a multifunctional phase-transformation nanocarrier to melanoma tumor. We successfully synthesized multifunctional nanoparticles (NPs) encapsulated with aPD1, iron oxide and perfluoropentane (PFP) in lactic-co-glycolic acid (PLGA) shell modified with poly ethylene glycol (PEG) and Gly-Arg-Gly-Asp-Ser (GRGDS) peptides (GOP@aPD1). In vitro, GOP@aPD1 NPs were characterized for particle size and drug-loading efficiency. The NPs were also tested for photothermal property, optical droplet vaporization (ODV) capacity and the ability of aPD1 release profile. In vivo, GOP@aPD1 NPs were systemically administered to melanoma-bearing mice demonstrated no toxicity and accumulation at tumor site. When mediated with PTT, this synergistic treatment achieved enhanced antitumor efficacy, due to combination of the effective aPD1 release and increased CD8+ T cell infiltration in tumor site. In conclusion, GOP@aPD1 NPs combined with PTT could potentiate the efficacy of aPD1 not only by tumor-targeted delivery of aPD1 but also by activating the immune system in the tumor microenvironment, which is a highly effective approach to treat melanoma.

The effect of Epigallocatechin-3-gallate on small intestinal morphology, antioxidant capacity and anti-inflammatory effect in heat-stressed broilers.

This study was to investigate the effects of Epigallocatechin-3-gallate (EGCG) on intestinal morphology, antioxidant capacity and anti-inflammatory response in heat-stressed broiler. A total of 192 2-week-old Arbour Acres broilers chickens were divided into four groups with six replicates per group and eight chickens per replicate: one thermoneutral control group (28°C, group TN), which was fed the basal diet; and three cyclic high-temperature groups (35°C from 7:00 to 19:00 hr; 28°C from 19:00 hr to 7:00 hr, heat stress group), which were fed the basal diet supplementation with EGCG 0 mg/kg (group HS0), 300 mg/kg (group HS300) and 600 mg/kg (group HS600). The gut morphology and intestinal mucosal oxidative stress indicators, as well as intestinal barrier-related gene expression, were analysed. The results showed that compared with group TN, heat stress reduced the villus height (VH), activities of glutathione peroxidase (GSH-Px), superoxide dismutase (SOD)and catalase (CAT), increased the crypt depth (CD) and malondialdehyde (MDA)content at 21, 28 and 35 days (p < 0.05). After the heat-stressed broilers were supplemented with EGCG, VH, VH/CD (V/C), and the activities of GSH-Px, SOD and CAT were increased, and CD and MDA content were reduced compared with those in group HS0 without EGCG supplementation at 21, 28 and 35 days (p < 0.05). The EGCG supplementation promoted the gene expression of nuclear factor-erythroid 2-related factor 2 (Nrf2), Claudin-1, Mucin 2 (Muc2) and alleviated the nuclear factor-kappa B (NF-κB) and lipopolysaccharide-induced tumour necrosis factor (LITAF) gene expression compared with group HS0 (p < 0.05). Moreover, intestinal morphology was strongly correlated with antioxidant ability and inflammatory response. In conclusion, EGCG alleviated the gut oxidative injury of heat-stressed broilers by enhancing antioxidant capacity and inhibiting inflammatory response.

Clinical features of long segmental myelopathy caused by nitrous oxide / 北京大学学报(医学版)

OBJECTIVE@#To analyze the clinical and imaging characteristics of the neurological damage caused by nitrous oxide (N2O).@*METHODS@#In the study, 10 patients in the Department of Neurology of China-Japan Friendship Hospital from October 2015 to February 2018 were retrospectively analyzed for the demographic data, the history of inhaled N2O, clinical features, blood examination, electrophysiological examination, spinal magnetic resonance imaging and therapeutic efficacy profiles.@*RESULTS@#The male-to-female ratio was 4:6 and it presented with an age-of-onset 17-26 years [the average age: (20.80±3.12) years]. The time from inhaled N2O to onset was 1 month to 1 year [the average time: (6.95±4.19) months]. Paralysis in all the patients and numbness in 9 patients were the main clinical features, while positive Lhermitte's sign in 3 patients, urinary and defecation disturbance in 4 patients were also found. Blood examination indicated anemia in 2 patients, giant cell anemia in 1 case and small cell hypochromic anemia in 1 case. 3 cases had been treated with vitamin B12 in an external hospital, and the other 7 cases had abnormal increase in homocysteine levels. Electrophysiological examinations showed sensory and motor nerve involvement in 9 patients, and motor nerve involvement in 1 patient. The severity of lower extremity lesion was significantly heavier than that of upper extremity. Spinal magnetic resonance imagings showed that long segmental lesions were present in the cervical spinal cord of all the patients, 3 cases with long segmental lesions of the thoracic cord and 2 cases with spinal cord swelling. In 6 cases, the horizontal axis had an "inverted V-type" T2 high signal, 1 case was classified as "crescent", and 3 cases were "eight-shaped". The symptoms in these 10 cases were alleviated in varying degrees after stopping the inhalation of nitrous oxide, actively supplementing high doses of vitamin B12 and doing early rehabilitation exercises.@*CONCLUSION@#Myelopathy with nitrous oxide presents as paralysis and numbness in limb extremities. In imaging, cervical spinal cord damage is common, accompanied by thoracic spinal cord damage. The horizontal axis is more common in the "inverted V-type". Treatment with high doses of vitamin B12 is effective.

The effects of inulin on the mucosal morphology and immune status of specific pathogen-free chickens.

This study investigated the effects of inulin on mucosal morphology and immune function of specific pathogen-free (SPF) chickens. A total of 200 one-day-old White Leghorns SPF chickens were divided into 5 groups of 4 replicates of 10 chickens each. All SPF chickens were fed a basal diet supplemented with 0, 0.25, 0.5, 1.0, or 2.0% inulin. The mucosal morphology and immune indexes were analyzed on days 7, 14, and 21, respectively. Our results showed that the concentrations of acetate and propionate in the cecum and serum had increased with dietary inulin supplementation on day 21 (P < 0.05). Butyrate could not be detected in the cecal digesta, but was increased in the serum of 1 and 2% groups, as compared with the control group (P < 0.05). The villi height was increased (P < 0.05) and the crypt depth was decreased (P < 0.05) in the duodenum and ileum of SPF chickens fed inulin, as compared with the control group. Also, inulin at a low concentration (0.25 or 0.5%) significantly decreased (P < 0.05) the gene expression of nuclear factor-κB (NF-κB), lipopolysaccharide-induced tumor necrosis factor (LITAF) at 7, 14, and 21 d, and of interleukin-6 (IL-6), and inducible nitric oxide synthase (iNOS) at 7 and 14 d, and increased that of mucin 2 (MUC2) and claudin-1 in the ileum of SPF chickens at 7, 14, and 21 d. High inulin supplementation (2%) significantly increased the gene expression of NF-κB, LITAF, IL-6, iNOS, and Claudin-1 at 14 and 21 d compared to low inulin concentration (0.25 or 0.5%). The results indicated that the effects of inulin on mucosal immune function occurred in a dose-dependent manner. A low concentration (0.25 or 0.5%) of inulin may be beneficial in promoting intestinal immune function.

Effect of epigallocatechin gallate on growth performance and serum biochemical metabolites in heat-stressed broilers.

This study aims to investigate the effects of epigallocatechin gallate (EGCG) on the growth performance and serum metabolic characteristics of heat-stressed broilers. A total of 192 14-day-old Arbor Acres broilers were divided into 4 groups with 6 replicates per group (8 chickens/cage). Thermoneutral group (Group TN) was fed the basal diet and maintained at 28°C for 24 h/d. The heat-stressed groups were housed at 35°C for 12 h/d and 28°C for 12 h/d and fed the basal diet supplemented with EGCG at 0, 300, and 600 mg/kg diet (Groups HS0, HS300, and HS600, respectively). The production performance and serum metabolic characteristics were analyzed at d 21, 28, and 35, respectively. At d 35 of age, heat stress reduced (P < 0.05) the body weight (BW), feed intake (FI) and the contents of serum total protein (TP) and glucose (GLU); inhibited (P < 0.05) alkaline phosphatase (ALP) activity; But increased (P < 0.05) the contents of uric acid (UA), cholesterol (CHOL), triglyceride (TG), and the activities of creatine kinase (CK), lactate dehydrogenase (LDH), aspartate aminotransferase (AST). Heat-stressed chickens fed EGCG exhibited a linear increase (P < 0.05) in BW, FI, the levels of serum TP, GLU, and ALP activity; and linear decrease (P < 0.05) in the contents of serum UA, CHOL, and TG, as well as the activities of LDH, CK, and AST. Heat stress also reduced (P < 0.05) the activities of serum glutathione peroxidase (GSH-Px), superoxide dismutase (SOD) and catalase (CAT) on d 35 and increased (P < 0.05) the GSH-Px and SOD activity on d 21 and malondialdehyde (MDA) contents. There was a linear increase (P < 0.05) in activities of GSH-Px, SOD and CAT at 35 d of age, and linear decreased (P < 0.05) in MDA contents. In conclusion, EGCG can improve the growth performance of broilers by enhancing antioxidant property and alleviating oxidant damage caused by heat stress.

Effect of epigallocatechin gallate on growth performance and antioxidant capacity in heat-stressed broilers.

This study investigated the effects of epigallocatechin gallate (EGCG) on the growth performance and antioxidant capacity of 35-d-old broilers exposed to heat stress. Broilers, 14 d of age, were divided into four groups with six replicates per group (eight chickens/replicate). Thermoneutral group (Group TN) was fed the basal diet and maintained at 28°C for 24 h/d. The heat-stressed groups were housed at 35°C for 12 h/d and 28°C for 12 h/d and fed the basal diet supplemented with EGCG at 0, 300 and 600 mg/kg diet (Groups HS0, HS 300 and HS600, respectively). Compared with Group TN, heat-stressed groups showed significantly reduced gain, feed intake and serum total protein and glucose levels; inhibited serum alkaline phosphatase activities; and increased serum levels of uric acid, cholesterol and triglycerides and the activity of serum creatine kinase, lactate dehydrogenase and aspartate aminotransferase (p < 0.05). Compared with Group HS0, Group HS600 exhibited an increased gain and feed intake; and normalised blood parameters and enzyme activities. Compared with Group TN, the expression of antioxidant-related liver proteins was decreased in Group HS0 and increased in Groups HS300 and HS600 (p < 0.05). The results suggest that EGCG can improve the growth performance and alleviate the oxidant damage by modulating the antioxidant properties of broilers.