A NETWORK PHARMACOLOGY-BASED TREATMENT ANALYSIS OF LUTEOLIN FOR REGULATING PYROPTOSIS IN ACUTE LUNG INJURY.

ABSTRACT: Background: Acute lung injury (ALI) and its severe manifestation, acute respiratory distress syndrome, are complicated pulmonary inflammatory conditions for which standard therapeutics are still not well established. Although increasing research has indicated the anti-inflammatory, anticancer, and antioxidant effects of luteolin, especially in lung diseases, the molecular mechanisms underlying luteolin treatment remain largely unclear. Methods: The potential targets of luteolin in ALI were explored using a network pharmacology-based strategy and further validated in a clinical database. The relevant targets of luteolin and ALI were first obtained, and the key target genes were analyzed using a protein-protein interaction network, Gene Ontology, and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses. The targets of luteolin and ALI were then combined to ascertain the relevant pyroptosis targets, followed by Gene Ontology analysis of core genes and molecular docking of key active compounds to the antipyroptosis targets of luteolin in resolving ALI. The expression of the obtained genes was verified using the Gene Expression Omnibus database. In vivo and in vitro experiments were performed to explore the potential therapeutic effects and mechanisms of action of luteolin against ALI. Results: Fifty key genes and 109 luteolin pathways for ALI treatment were identified through network pharmacology. Key target genes of luteolin for treating ALI via pyroptosis were identified. The most significant target genes of luteolin in ALI resolution included AKT1, NOS2, and CTSG. Compared with controls, patients with ALI had lower AKT1 expression and higher CTSG expression. Luteolin simply reduced systemic inflammation and lung tissue damage in septic mice. Furthermore, we blocked AKT1 expression and found luteolin reduced the degree of lung injury and affected NOS2 levels. Conclusions: As demonstrated by a network pharmacology approach, luteolin may exert an antipyroptosis effect on ALI via AKT1, NOS2, and CTSG.

Identification of two key UDP-glycosyltransferases responsible for the ocotillol-type ginsenoside majonside-R2 biosynthesis in Panax vietnamensis var. fuscidiscus.

MAIN CONCLUSION: Two UDP-glycosyltransferases from Panax vienamensis var. fuscidiscus involved in ocotillol-type ginsenoside MR2 (majonside-R2) biosynthesis were identified. PvfUGT1 and PvfUGT2 sequentially catalyzes 20S,24S-Protopanxatriol Oxide II and 20S,24R-Protopanxatriol Oxide I to pseudoginsenoside RT4/RT5 and RT4/RT5 to 20S, 24S-MR2/20S, 24S-MR2. Ocotilol type saponin MR2 (majonside-R2) is the main active component of Panax vietnamensis var. fuscidiscus (commonly known as 'jinping ginseng') and is well known for its diverse pharmacological activities. The use of MR2 in the pharmaceutical industry currently depends on its extraction from Panax species. Metabolic engineering provides an opportunity to produce high-value MR2 by expressing it in heterologous hosts. However, the metabolic pathways of MR2 remain enigmatic, and the two-step glycosylation involved in MR2 biosynthesis has not been reported. In this study, we used quantitative real-time PCR to investigate the regulation of the entire ginsenoside pathway by MeJA (methyl jasmonate), which facilitated our pathway elucidation. We found six candidate glycosyltransferases by comparing transcriptome analysis and network co-expression analysis. In addition, we identified two UGTs (PvfUGT1 and PvfUGT2) through in vitro enzymatic reactions involved in the biosynthesis of MR2 which were not reported in previous studies. Our results show that PvfUGT1 can transfer UDP-glucose to the C6-OH of 20S, 24S-protopanaxatriol oxide II and 20S, 24R-protopanaxatriol oxide I to form pseudoginsenoside RT4 and pseudoginsenoside RT5, respectively. PvfUGT2 can transfer UDP-xylose to pseudoginsenoside RT4 and pseudoginsenoside RT5 to form 20S, 24S-MR2 and 20S, 24S-MR2. Our study paves the way for elucidating the biosynthesis of MR2 and producing MR2 by synthetic biological methods.

Craniocervical Manual Lymphatic Drainage Increases the Efficiency of Atorvastatin-Based Treatment of Chronic Subdural Hematoma.

The objective of this study is to explore whether craniocervical manual lymphatic drainage (cMLD) can promote hematoma absorption and increase the efficiency of atorvastatin-based conservative treatment in chronic subdural hematoma (CSDH) patients. All CSDH patients treated with atorvastatin-based therapy between October 2020 and February 2022 in our department were retrospectively screened for enrollment. The patients were divided into the control and cMLD groups according to whether cMLD was performed. Head CT or MR images in both groups were obtained before the treatment and 2 weeks and 4 weeks after the treatment. MR images of the deep cervical lymphatic nodes (dCLNs) in 23 patients were obtained in the cMLD group before and approximately 2 weeks after treatment. The volumes of the dCLNs and hematoma were calculated. The primary outcomes are the differences in hematoma volume reduction after 4 weeks of treatment. The secondary outcomes were (1) the differences in hematoma volume reduction between the patients in these two groups in the 2nd week, (2) the dCLN volume change in the cMLD group before and after 2 weeks of treatment, and (3) the percentage of patients who transitioned to surgery because of failure to the conservative treatment. A total of 106 consecutive patients were enrolled in this study for analysis; 54 patients received atorvastatin-based treatment (control group), and 52 were treated with both atorvastatin-based treatment and cMLD (cMLD group). At baseline, the mean hematoma volume was 76.53 ± 42.97 ml in the control group and 88.57 ± 49.01 ml in the cMLD group (p = 0.181). In the 4th week, the absolute number of hematoma reductions (20.79 ± 34.73 ml vs. 37.28 ± 28.24 ml, p = 0.009) and percentage of hematoma reductions (22.58% ± 60.01% vs. 46.43% ± 30.12%, p = 0.012) in the cMLD group were greater than those in the control group. After 2 weeks of treatment, the absolute number of hematoma reductions showed no difference in the two groups, while the percentage of hematoma reduction was higher in the cMLD group (18.18% ± 24.61% vs. 2.08% ± 25.72%, p = 0.001). One patient in cMLD and 8 patients in the control group were transitioned to receive surgical treatment. The dCLN volumes in 23 experimental patients increased significantly after 2 weeks of treatment in the cMLD group (p = 0.032). There were no severe side effects that needed to be reported. Combined with atorvastatin-based therapy, cMLD can promote hematoma absorption and decrease the surgery rate, which provides a new therapeutic strategy for CSDH.

Possible mechanism and Atorvastatin-based treatment in cupping therapy-related subdural hematoma: A case report and literature review.

Subdural hematoma (SDH) is one of the most lethal types of traumatic brain injury. SDH caused by Intracranial Pressure Reduction (ICPR) is rare, and the mechanism remains unclear. Here, we report three cases of SDH that occurred after substandard cupping therapy and are conjected to be associated with ICPR. All of them had undergone cupping treatments. On the last cupping procedure, they experienced a severe headache after the cup placed on the occipital-neck junction (ONJ) was suddenly removed and were diagnosed with SDH the next day. In standard cupping therapy, the cups are not usually placed on the ONJ. We speculate that removing these cups on the soft tissue over the cisterna magna repeatedly created localized negative pressure, caused temporary but repeated ICPR, and eventually led to SDH development. The Monro-Kellie Doctrine can explain the mechanism behind this - it states that the intracranial pressure is regulated by a fixed system, with any change in one component causing a compensatory change in the other. The repeated ICPR promoted brain displacement, tearing of the bridging veins, and development of SDH. The literature was reviewed to illustrate the common etiologies and therapies of secondary ICPR-associated SDH. Despite the popularity of cupping therapy, its side effects are rarely mentioned. This case is reported to remind professional technicians to fully assess a patient's condition before cupping therapy and ensure that the cups are not placed at the ONJ.

Developmental Characteristics and Auxin Response of Epiphytic Root in Dendrobium catenatum.

Dendrobium catenatum, a traditional precious Chinese herbal medicine, belongs to epiphytic orchids. Its special life mode leads to the specialization of roots, but there is a lack of systematic research. The aerial root in D. catenatum displays diverse unique biological characteristics, and it initially originates from the opposite pole of the shoot meristem within the protocorm. The root development of D. catenatum is not only regulated by internal cues but also adjusts accordingly with the change in growth environments. D. catenatum root is highly tolerant to auxin, which may be closely related to its epiphytic life. Exogenous auxin treatment has dual effects on D. catenatum roots: relatively low concentration promotes root elongation, which is related to the induced expression of cell wall synthesis genes; excessive concentration inhibits the differentiation of velamen and exodermis and promotes the overproliferation of cortical cells, which is related to the significant upregulation of WOX11-WOX5 regeneration pathway genes and cell division regulatory genes. Overexpression of D. catenatum WOX12 (DcWOX12) in Arabidopsis inhibits cell and organ differentiation, but induces cell dedifferentiation and callus production. Therefore, DcWOX12 not only retains the characteristics of ancestors as stem cell regulators, but also obtains stronger cell fate transformation ability than homologous genes of other species. These findings suggest that the aerial root of D. catenatum evolves special structure and developmental characteristics to adapt to epiphytic life, providing insight into ideal root structure breeding of simulated natural cultivation in D. catenatum and a novel target gene for improving the efficiency of monocot plant transformation.

[Influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks: a Meta analysis]. / 脐带挤压与延迟断脐对胎龄<34周早产儿早期预后影响的Meta分析.

OBJECTIVES: To study the influence of umbilical cord milking versus delayed cord clamping on the early prognosis of preterm infants with a gestational age of <34 weeks. METHODS: PubMed, Web of Science, Embase, the Cochrane Library, CINAHL, China National Knowledge Infrastructure, Wanfang Data, Weipu Database, and SinoMed were searched for randomized controlled trials on umbilical cord milking versus delayed cord clamping in preterm infants with a gestational age of <34 weeks published up to November 2021. According to the inclusion and exclusion criteria, two researchers independently performed literature screening, quality evaluation, and data extraction. Review Manger 5.4 was used for Meta analysis. RESULTS: A total of 11 articles were included in the analysis, with 1 621 preterm infants in total, among whom there were 809 infants in the umbilical cord milking group and 812 in the delayed cord clamping group. The Meta analysis showed that compared with delayed cord clamping, umbilical cord milking increased the mean blood pressure after birth (weighted mean difference=3.61, 95%CI: 0.73-6.50, P=0.01), but it also increased the incidence rate of severe intraventricular hemorrhage (RR=1.83, 95%CI: 1.08-3.09, P=0.02). There were no significant differences between the two groups in hemoglobin, hematocrit, blood transfusion rate, proportion of infants undergoing phototherapy, bilirubin peak, and incidence rates of complications such as periventricular leukomalacia and necrotizing enterocolitis (P>0.05). CONCLUSIONS: Compared with delayed cord clamping, umbilical cord milking may increase the risk of severe intraventricular hemorrhage in preterm infants with a gestational age of <34 weeks; however, more high-quality large-sample randomized controlled trials are needed for further confirmation.

The occurrence and partition of total petroleum hydrocarbons in sediment, seawater, and biota of the eastern sea area of Shandong Peninsula, China.

To investigate the occurrence and partition of total petroleum hydrocarbons (TPHs), sediment, seawater, and biota of the eastern sea area of Shandong Peninsula (China) were sampled in 2016. Due to shipping activities and discharge of industrial wastes, the TPH levels in the sediment decreased from the coastal areas to the offshore area. Waterborne TPH concentrations showed a decreasing order of autumn > summer > spring > winter, probably caused by low input of pollutants from the river into the ocean in dry seasons and frequent aquaculture operations in wet seasons. The distribution coefficient (logKd) between sediment and seawater ranged from 2.00 to 5.05, suggesting that TPHs are preferentially retained by the sediment. Significant positive correlations between logKd and total organic carbon (TOC), mud (fine particles), and temperature, as well as negative correlations between logKd and dissolved oxygen (DO), hydrogen ion concentration (pH), and oxidation-reduction potential (Eh), suggest interactions between environmental behaviors of TPHs and physicochemical factors. Mean bioaccumulation factors (BAFs) of TPHs in fish, shrimps, and mollusks were determined to be 240 ± 200, 900 ± 1800, and 2630 ± 1280, respectively, suggesting that considerable bioaccumulation occurs in shrimps when TPHs are transported from the seawater to the shrimps. A negative linear correlation between logTPHs and trophic level indicated biodilution of TPHs along the marine food web. This is the first study that has focused on the accumulation of TPHs in the entire sediment-seawater-biota system.

Naringenin is a Potential Anabolic Treatment for Bone Loss by Modulating Osteogenesis, Osteoclastogenesis, and Macrophage Polarization.

Bone undergoes constant remodeling of formation by osteoblasts and resorption by osteoclasts. In particular, macrophages have been reported to play an essential role in the regulation of bone homeostasis and regeneration. Naringenin, the predominant flavanone in citrus fruits, is reported to exert anti-inflammatory, anti-osteoclastic, and osteogenic effects. However, whether naringenin could modulate the crosstalk between macrophages and osteoblasts/osteoclasts remains to be investigated. In this study, we confirmed that naringenin enhanced osteogenesis and inhibited osteoclastogenesis directly. Naringenin promoted M2 transition and the secretion of osteogenic cytokines including IL-4, IL-10, BMP2, and TGF-ß, while suppressing LPS-induced M1 polarization and the production of proinflammatory factors such as TNF-α and IL-1ß. In addition, the coculture of primary bone mesenchymal stem cells (BMSCs)/bone marrow monocytes (BMMs) with macrophages showed that the naringenin-treated medium significantly enhanced osteogenic differentiation and impeded osteoclastic differentiation in both inflammatory and non-inflammatory environment. Moreover, in vivo experiments demonstrated that naringenin remarkably reversed LPS-induced bone loss and assisted the healing of calvarial defect. Taken together, naringenin serves as a potential anabolic treatment for pathological bone loss.

Gamma-oryzanol protects human liver cell (L02) from hydrogen peroxide-induced oxidative damage through regulation of the MAPK/Nrf2 signaling pathways.

Gamma-oryzanol (Orz), a mixture of the ferulic acid ester of triterpene alcohols and phytosterols, was found abundantly in rice bran and rice bran oil which could be available and served as an antioxidant. The present study was to explore the potential protective effects of Orz on oxidative stress and cell apoptosis in human hepatic cells (L02 cells) induced by hydrogen peroxide (H2 O2 ). Flow cytometry detection and Hoechst 33258 staining showed that Orz significantly restored cell cycle and ameliorated apoptosis in H2 O2 -challenged L02 cells. Orz pretreatment inhibited H2 O2 -induced cell apoptosis by increasing the scavenging of hydroxyl radicals (OH·), and efficiently decreasing the production of nitric oxide (NO). Moreover, a loss of total antioxidant capacity (T-AOC) and adenosine triphosphatase (ATPase) were enhanced in H2 O2 -mediated L02 cells pretreated with Orz. Furthermore, preincubation with Orz reduced H2 O2 -mediated the proapoptotic protein of Bak expression and the phosphorylation of ASK1, p38, JNK, and ERK, and increased the anti-apoptotic protein of Bcl-xl expression and anti-oxidative stress proteins of Nrf2 and HO-1 expression. The findings suggested that Orz exerts the cytoprotective effects in H2 O2 -induced L02 cells apoptosis by ameliorating oxidative stress via inhibiting MAPK signaling pathway and activating Nrf2 signaling pathway. PRACTICAL APPLICATIONS: Gamma-oryzanol (Orz), a mixture of the ferulic acid ester of triterpene alcohols and phytosterols, was found abundantly in rice bran and rice bran oil which could be availably served as an antioxidant. In this study, it was found that Orz exerts the cytoprotective effects in H2 O2 -induced L02 cell apoptosis by ameliorating oxidative stress via the inhibition of MAPK signaling pathway and the activation of Nrf2 signaling pathway, which provides a theoretical basis for dietary adding natural products to prevent or treat oxidative stress-related diseases.

Dexamethasone enhances the efficacy of atorvastatin in inhibiting excessively inflammation-induced abnormal angiogenesis by regulating macrophages.

BACKGROUND: We have recently showed that atorvastatin (ATO) combined with low dose of dexamethasone (DEX) was more efficacious in treating patients with chronic subdural haematoma (CSDH) than ATO monotherapy. This study was designed to investigate the underlying mechanisms of the improved efficacy of this combined therapy. METHODS: Mass spectrometry was performed to quantitatively detect drugs in haematoma fluids and serum samples from CSDH patients and also in cultured macrophages after treatment with either ATO alone or in combination with DEX. The differentiation and apoptosis of macrophages were evaluated using flow cytometry. The expression of cytokines, chemokines and angiogenesis-related proteins was evaluated using proteome profile arrays, immunoblots and ELISA, respectively. RESULTS: ATO was detected in haematoma fluids and serum samples, whose levels were increased significantly in samples collected from patients treated with both ATO and DEX. ATO was also increased in cultured macrophages treated with ATO and DEX. The numbers of M1-polarized macrophages were higher than the M2 phenotype in the haematoma fluids of patients. Cultured macrophages treated with ATO and DEX had reduced numbers of M1-polarized macrophages, increased numbers of M2-polarized macrophages as compared to monotherapies, and decreased rate of apoptosis induced by high-dose DEX. DEX enhanced the anti-inflammatory and anti-angiogenic activity of ATO by suppressing VEGFA and other inflammatory angiogenic factors. Consistent with the finding, patients responded well to the drug treatments had lower serum levels of VEGFA. CONCLUSIONS: We have shown for the first time that ATO given orally was detected in CSDH haematoma fluids. DEX enhances the anti-inflammatory and anti-angiogenic effects of ATO, primarily by increasing the presence of ATO in haematoma and macrophages and by regulating the functions of macrophages.

Alkaloid Extract of Moringa oleifera Lam. Exerts Antitumor Activity in Human Non-Small-Cell Lung Cancer via Modulation of the JAK2/STAT3 Signaling Pathway.

Lung cancer is one of the most common malignant tumors diagnosed worldwide. Moringa oleifera Lam. is a valuable medicinal plant native to India and Pakistan. However, the antilung cancer activity of M. oleifera alkaloid extract (MOAE) is unknown. The present study aimed to evaluate the regulatory effect of MOAE on A549 cells by examination of the proliferation, apoptosis, cell cycle, and migration of cells and to elucidate the possible mechanism of action of MOAE. We tested five types of cancer cells and four types of lung cancer cells and found MOAE exerted the strongest growth inhibitory effect against A549 cells but had low toxicity to GES-1 cells (human gastric mucosal epithelial cells). Simultaneously, MOAE induced apoptosis and increased the expression of the apoptosis-related proteins caspase-3 and caspase-9 in A549 cells. Furthermore, MOAE induced cell cycle arrest in the S phase through a decrease in the expression of the proteins cyclin D1 and cyclin E and an increase in the expression of the protein p21. MOAE also inhibited the migratory ability of A549 cells and decreased the expression of the migration-related proteins, matrix metalloproteinase (MMP) 2 and MMP9. In addition, the phosphorylation level of JAK2 and STAT3 proteins was decreased in MOAE-treated A549 cells. Furthermore, AZD1480 (a JAK inhibitor) and MOAE inhibited the proliferation and migration of A549 cells and induced cell apoptosis, and the effects of MOAE and AZD1480 were not additive. These results indicated that MOAE inhibits the proliferation and migration of A549 cells and induces apoptosis and cell cycle arrest through a mechanism that is related to the inhibition of JAK2/STAT3 pathway activation. Thus, this extract has potential for preventing and treating lung cancer.

The effect of a selected yeast fraction on the prevention of pullorum disease and fowl typhoid in commercial breeder chickens.

A selected yeast fraction (SYF) was tested for the purpose of preventing pullorum disease and fowl typhoid in breeder chickens. In a challenge-protection experiment, commercial Three-Yellow breeder chicks were initially divided into groups A, B (challenged, treated), C (challenged, untreated), and D (unchallenged, untreated). The group A diet was supplemented with SYF and group B was supplemented with Acidipure via drinking water. At 7 D, birds of groups A, B, and C were divided into 2 equal subgroups (A1-A2, B1-B2, and C1-C2). Subgroups A1, B1, and C1 were challenged with Salmonella pullorum (SP), while subgroups A2, B2, and C2 were challenged with Salmonella gallinarum (SG). Clinical signs and mortality were recorded daily. At intervals, antibodies against SP and SG were detected by a plate agglutinate test (PAT). At 42 D, all birds were weighed and necropsied, lesions were recorded and challenge pathogens were isolated. Results showed that SP and SG isolation positive rates of groups A1-A2 were significantly lower (P < 0.05) than those of B1-B2 and C1-C2, respectively. The average body weight (BW) of groups A1-A2 was significantly higher (P < 0.05) than that of B1-B2 and C1-C2, respectively. In the field trial, chicks were randomly divided into 3 groups. Group 1 birds were fed a diet supplemented with SYF, group 2 diet was supplemented with Acidipure via drinking water, and group 3 was fed the same but un-supplemented diet as the control group. Antibodies against SP and SG were detected by PAT at 120 D. The antibodies positive rate of group 1 was significantly lower (P < 0.05) than those of groups 2 and 3, while no significant difference (P > 0.05) was found between groups 2 and 3. The results demonstrated that SYF supplementation could significantly decrease SP and SG infection rates, improve the BW of birds challenged with SP and SG, and was more effective than Acidipure via drinking water.

Application of enhanced recovery after surgery during the perioperative period in infants with Hirschsprung's disease - A multi-center randomized clinical trial.

BACKGROUND & AIMS: Various enhanced recovery after surgery (ERAS) guidelines have been established for several kinds of adult surgeries. While the guidelines for pediatric surgeries remained to be explored. The aim of the study was to prospectively evaluate the safety and efficacy of an ERAS protocol for Hirschsprung's disease (HSCR) infants undergoing pull-through procedures. METHODS: An infant-specific ERAS protocol was developed and implemented at multiple centers from June 1, 2016 to December 31, 2017. The study included 145 consecutive patients who underwent pull-through surgery for HSCR in three Children's hospitals. Patients were primarily divided into three groups based on the clinical classification and surgical methods. Group I included patients with the short segment type who received transanal endorectal pull-through (TEPT) surgery. Group II comprised of patients with the classical type and long segment type who received laparoscopic-assisted pull-through (LAPT) surgery. Group III involved patients with the long segment type (who had received ileostomy or colostomy during the neonatal period) and total colonic aganglionosis who received open pull-through (OPPT) surgery. Patients in the three groups mentioned above were randomly and equally assigned into the ERAS group and traditional (TRAD) group with random number table row randomization. The primary outcome was the length of postoperative hospital stay (LOS). Secondary outcomes of interest included white blood cell (WBC) and C-reactive protein (CRP) on postoperative day 1 (POD 1), the blood glucose at the time of anesthesia and 24 h after surgery, time to first defecation, time to regular diet, plasma markers of nutrition status on POD 5, plasma natrium on POD 5, the mean intraoperative fluid volume, time to discontinuation of intravenous infusion, incidence of postoperative complications, re-admission within 30 days, hospitalization costs, parental satisfaction, and growth from admission to 6 months after surgery. RESULTS: 73 and 75 patients were assigned to the TRAD and ERAS groups, respectively. There were no significant differences in demographic data. The LOS decreased from 9.5 days in the TRAD group to 7.9 days (P < 0.001) in the ERAS group. WBC count on POD 1 showed no significant difference between the two groups. CRP on POD 1 in the ERAS group was significantly lower (P < 0.001). In the ERAS group, the blood glucose was higher at anesthesia compared to the TRAD group (P < 0.001). On the contrary, the blood glucose at 24 h after surgery was significantly lower in the ERAS group (P < 0.001). Intraoperative fluid volume was lower in the EARS group (P < 0.001). ERAS could also reduce the time to first defecation (P < 0.001), discontinuation of intravenous infusion (P < 0.001) and regular diet (P < 0.001). In the ERAS group, the concentrations of prealbumin and retinol conjugated protein on POD 5 were higher than those in the TRAD group (P < 0.001, P < 0.001, respectively). The plasma natrium had no difference in the two groups on POD 5 (P > 0.05). The rate of complications (P > 0.05) and 30-day re-admission (P > 0.05) were not significantly different between the two groups. Hospitalization costs were also reduced (P < 0.001). ERAS group has a higher parental satisfaction rate, although there was no statistical difference (96% vs 89%). There was no difference in growth between the ERAS and the TRAD groups from admission to 6 months after the surgery (weight for age z score: P > 0.05, weight for length z score: P > 0.05). We also found that the shortening of LOS by the application of ERAS protocol was more obvious in the OPPT group (-2.5 ± 1.0) than that in the TEPT (-1.9 ± 1.3) and LAPT (-1.3 ± 0.4) groups. CONCLUSIONS: Implementation of the ERAS protocol in infants undergoing HSCR pull-through operations is safe and efficient. The ERAS protocol is worthy of recommendation. TRIAL REGISTRATION: Clinical Trials.gov identifier: NCT02776176.

Biomineralized Gd2 O3 @HSA Nanoparticles as a Versatile Platform for Dual-Modal Imaging and Chemo-Phototherapy-Synergized Tumor Ablation.

A great challenge still remains to explore the facile approaches to construct multifunctional nanoparticles for acquiring precise cancer theranostics. Herein, a biocompatible theranostic nanoplatform capable of simultaneous cancer imaging and therapy is attempted by loading of paclitaxel (PTX) and indocyanine green (ICG) molecules into the matrix of Gd2 O3 @human serum albumin (HSA) nanoparticles (PIGH NPs) via hydrophobic interaction. The subsequent in vitro investigations reveal that the PIGH NPs afford uniform particle size, sustained drug release profile, strong longitudinal relaxivity, potent photothermal effect, effective singlet oxygen generation, and ideal resistance to photobleaching. Moreover, the PIGH NPs achieve high cellular uptake, efficient cytoplasmic drug translocation based on singlet oxygen-triggered endolysosomal disruption and prominent cytotoxicity effect against 4T1 cells under 808 nm near-infrared (NIR) irradiation in contrast to PTX/ICG-loaded HSA nanoparticles (PIH NPs) and free PTX/ICG. After intravenous injection, the PIGH NPs exhibit preferable tumor accumulation and achieve effective tumor ablation in 4T1 tumor bearing mouse model with excellent dual near-infrared fluorescence/magnetic resonance (NIRF/MR) imaging guided synergistic chemo-phototherapy. Hence, the PIGH NPs can be utilized as potential theranostic nanosystem for simultaneous cancer imaging and therapy.

Case report and review of the literature of primary gastrointestinal amyloidosis diagnosed with enteroscopy and endoscopic ultrasonography.

Here, we report a rare case of primary gastrointestinal amyloidosis in a stable condition after being followed up for three years. The patient was admitted to the hospital in 2014. Tests showed decreased levels of hemoglobin and ferritin. Transoral and transanal enteroscopy showed multiple nodular protuberances in the esophagus, ileum, colon and rectum. Endoscopic ultrasonography indicated the nodular protuberances stemmed from the submucosa and partially invaded the intrinsic myometrium. Pathological examinations found multiple small nodules in the submucosa and dyed structures, which were positive for special Congo red dyeing. After treatment with oral iron supplements, the levels of hemoglobin and ferritin became normal. It is concluded that the patient represents a case of primary gastrointestinal amyloidosis with multiple nodular protuberances in the digestive tract with controllable moderate abdominal discomfort and anemia and a benign course. Enteroscopy and endoscopic ultrasonography play an important role in the diagnosis of primary gastrointestinal amyloidosis.

Artesunate attenuated progression of atherosclerosis lesion formation alone or combined with rosuvastatin through inhibition of pro-inflammatory cytokines and pro-inflammatory chemokines.

BACKGROUNDS: Inflammation plays an important role in all stages of atherosclerosis, but little is known about the therapeutic effects of quenching inflammation in atherosclerotic lesions formation. PURPOSE: Herein, the effect of artesunate, a derivant from artemisinin from the traditional Chinese herb sweet wormwood, could attenuate the progression of atherosclerosis lesion formation alone or combined with rosuvastatin in Western-type diet (WD) fed ApoE(-/-) mice, and explored its possible mechanisms. METHODS: The methods such as ELISA for plasma lipids and cytokines analyses, qRT-PCR and western blot for mRNA and protein expressions, and MTT assay for human umbilical vein endothelial cells (HUVECs) viability were used for in vivo and in vitro experiments. RESULTS: Artesunate could attenuate the progression of atherosclerosis lesion formation alone or combined with rosuvastatin in WD fed ApoE(-/-) mice without changes in food uptake, body weight and plasma lipids level, but with a significant reduction of pro-inflammatory cytokine, such as TNF-α and IL-6. Furthermore, artesunate could down-regulate the pro-inflammatory chemokines such as IL-8 and MCP-1 in aorta of mice. Besides, artesunate didn't influence IL-8 and MCP-1 secretion in HUVECs up-regulated by TNF-α, but inhibited IL-8 and MCP-1 secretion up-regulated by LPS. CONCLUSION: AS attenuated progression of atherosclerosis lesion formation alone or combined with rosuvastatin through anti-inflammatory effect, resulting in down-regulation of TNF-α and IL-6, and further down-regulating IL-8 and MCP-1 expressions in aorta of WD fed ApoE(-/-) mice. Rosuvastatin combined with artesunate could more effectively attenuate the progression of atherosclerosis lesions than when treated by one of them, demonstrating that lipid-lowering agents combined with anti-inflammatory agents could provide the greater benefit for cardiovascular disease patients. Artesunate is worth further investigating as a candidate drug for the treatment of atherosclerosis.

Obscurumines H-P, new Lycopodium alkaloids from the club moss Lycopodium obscurum.

Seven new fawcettimine-type (1-7) and two new lycopodine-type (8 and 9) Lycopodium alkaloids, as well as 10 known compounds, were isolated from the club moss, Lycopodium obscurum L. The structures of obscurumines H-P (1-9) were determined based on high-resolution MS and 1D and 2D NMR data. Compounds 1 and 2 include a new skeleton that is formed via the linkage of C-9-N-2', which is rarely present in Lycopodium alkaloids. The in vitro acetylcholinesterase (AChE) inhibitory activity assay showed that 5 exhibited weak anti-AChE activity with an IC50 value of 81.0 µM. Compound 8 exhibited inhibition of the secretion of IL-2 in phytohemagglutinin (PHA) and phorbol myristate acetate (PMA) stimulated Jurkat cells, and the IC50 value was 17.2 µM.

Emodin is identified as the active component of ether extracts from Rhizoma Polygoni Cuspidati, for anti-MRSA activity.

This study investigated the anti-methicillin-resistant Staphylococcus aureus (anti-MRSA) activity and chemical compositions of ether extracts from Rhizoma Polygoni Cuspidati (ET-RPC). Significant anti-MRSA activities of ET-RPC against MRSA252 and MRSA clinical strains were tested in in vitro antibacterial experiments, such as inhibition zone diameter test, minimal inhibitory concentration test, and dynamic bacterial growth assay. Subsequently, 7 major compounds of ET-RPC were purified and identified as polydatin, resveratrol-4-O-d-(6'-galloyl)-glucopyranoside, resveratrol, torachryson-8-O-glucoside, emodin-8-O-glucoside, 6-hydroxy-emodin, and emodin using liquid chromatography - electrospray ionization - tandem mass spectrometry. After investigation of anti-MRSA activities of the 7 major compounds, only emodin had significant anti-MRSA activity. Further, transmission electron microscopy was used to observe morphological changes in the cell wall of MRSA252, and the result revealed that emodin could damage the integrity of cell wall, leading to loss of intracellular components. In summary, our results showed ET-RPC could significantly inhibit bacterial growth of MRSA strains. Emodin was identified as the major compound with anti-MRSA activity; this activity was related to destruction of the integrity of the cell wall and cell membrane.

Huperserines A-E, Lycopodium alkaloids from Huperzia serrata.

A phytochemical study on Huperzia serrata led to the isolation of four new 5-deoxyfawcettimine-related Lycopodium alkaloids, huperserines A-D (1-4), and one new lycodine-type alkaloid, huperserine E (5). Their structures were elucidated based on spectroscopic data, including 1D and 2D NMR techniques. 5-Carbonyl or 5-hydroxyl group is a typical characteristic of lycopodine- and fawcettimine-type alkaloids. This is the first report of the 5-deoxyfawcettimine type Lycopodium alkaloids. In vitro acetylcholinesterase (AChE) inhibitory activity assay showed that huperserine E exhibited moderate anti-AChE activity with an IC50 value of 6.71 µM.

[Inhibition effects of black rice pericarp extracts on cell proliferation of PC-3 cells].

OBJECTIVE: To observe the inhibitive effects of black rice pericarp extracts on cell proliferation of human prostate cancer cell PC-3 and to explore its effecting mechanism. METHODS: The black rice pericarp extract was used to treat the PC-3 cells. The inhibitory effect of black rice pericarp extract on cells proliferation of PC-3 was tested by MTT method. Cell apoptosis rates and cell cycle were measured by flow cytometric assay (FCM). Western blot was used to study the protein expression levels of p38, p-p38, JNK, p-JNK. RESULTS: A dose-dependent and time-dependent proliferation inhibition of black rice pericarp extract was demonstrated in PC-3. The most prominent experiment condition was inhibitory concentration with 300microg/ml and treated for 72 h. The experiment result of flow cytometry analysis demonstrates that the apoptosis rate of PC-3 cells increased along with the increasing of black rice pericarp extract concentration, and a G1-S cell cycle arrest was induced in a dose-dependent manner. After PC-3 cell was treated with black rice pericarp extract for 72 h, the expressions of p-p38, p-JNK protein increased. CONCLUSION: Black rice pericarp extract could inhibit proliferation, change the cell cycle distributions and induce apoptosis in human prostatic cancer cell PC-3. Its inhibitory effect may be through promoting activation of the JNK, p38 signaling pathway. These results suggest that black rice pericarp extract maybe has an inhibitory effect on prostatic cancer.