Screening Five Qi-Tonifying Herbs on M2 Phenotype Macrophages.

Tumor-associated macrophages (TAMs) with M2 phenotype play an essential role in tumor microenvironment (TME) during the progression and development of numerous cancers and associated with poor prognosis. Thus, regulation of TAMs polarization emerged as a new strategy for tumor immune therapy. According to Traditional Chinese Medicine (TCM) theory, herbs with Qi-tonifying character are involved in improving the defense capacity of immune system. In this study, we screened extracts and ingredients from five Qi-tonifying herbs exhibiting an inhibitory effect on M2 polarization of murine macrophages RAW264.7 induced by IL-4 and IL-13. Among these candidates, total flavonoids from Glycyrrhiza Radix et Rhizoma (TFRG) and ethanol extract of Ginseng Radix et Rhizoma significantly inhibited the expression of Arginase-1 (Arg-1) (above 90% at 100µg/mL), one of the phenotype markers of M2 macrophages. The inhibition of total saponins of Ginseng Radix et Rhizoma, ethanol extract of Cordyceps, ethanol extract of Acanthopanacis senticosi Radix et Rhizoma Seu caulis, and ethanol extract of Astragali Radix reached above 50% at 100µg/mL. The inhibition of ingredients including glabridin, isoliquiritin apioside, lysionotin, cordycepin, astragaloside IV, and calycosin reached above 50% at 50µM. Then, we investigated the molecular mechanisms of TFRG. TFRG abolished the migration of murine breast cancer 4T1 stimulated by the conditioned medium from M2 macrophages (M2-CM). In addition to Arg-1, TFRG also antagonized the IL-4/13-mediated mRNA upregulation of the M2 markers including found in inflammatory zone 1 (FIZZ1), chitinase-3-like protein 3 (YM1), and mannose receptor (CD206) and upregulated the expression of inducible nitric oxide synthase (iNOS), one of the M1 markers. The further exploration showed that TFRG decreased the phosphorylation of STAT6 and increased the expression of miR-155. Our study provides a series of potential immune regulating natural products from five Qi-tonifying herbs on M2 phenotype. For instance, TFRG suppressed M2 polarization of macrophages partly by inactivating STAT6 pathway and enhanced the level of miR-155 to regulate the expressions of M1 and M2 markers.

Ethyl Acetate Fraction from Hedyotis diffusa plus Scutellaria barbata Exerts Anti-Inflammatory Effects by Regulating miR-155 Expression and JNK Signaling Pathway.

Hedyotis diffusa Willd and Scutellaria barbata D. Don (HDSB) were the core couplet in medicines that were commonly used for the purpose of anti-inflammation and anticancer treatments in China. However, biological properties of this couplet have not been fully elucidated. In this study, we screened fractions of HDSB for their anti-inflammatory activities and explored pertinent molecular mechanisms on murine macrophage RAW264.7 cell model. Ethyl acetate fraction from the aqueous extract of the couplet at equal weight ratio (EA11) showed the strongest inhibition of the nitrite accumulation in supernatant of RAW264.7 cells stimulated with lipopolysaccharide (LPS)/interferon-γ (IFN-γ). In addition, EA11 inhibited iNOS and IL-1ß expression in a concentration-dependent manner while promoting the expression of HO-1 and PPAR-γ. Anti-inflammatory capability is most likely facilitated by its inhibitory effect on JNK signaling pathway and miR-155 expression. This study suggests that EA11 may be represented as a potential anti-inflammatory therapeutic candidate.

Analysis of bilirubin UDP-glucuronosyltransferase gene mutations in an unusual Crigler-Najjar syndrome patient.

Crigler-Najjar (CN) syndrome is a rare autosomal recessive inherited disorder characterized by non-hemolytic, unconjugated hyperbilirubinemia. The levels of serum bilirubin and the response to phenobarbital treatment have been used to classify CN syndrome into two types: CN I and II. Mutations of the UGT1A1 gene have been found to be responsible for cases of CN syndrome. In the present study, the clinical features of a boy with an unusual type of CN syndrome were analysed. A DNA sample was obtained from the patient, and the promoter region, the exons and flanking intronic sequences of the UGT1A1 gene were analysed using the polymerase chain reaction and sequencing. The case was similar to CN type I in clinical features, but the therapeutic efficacy in the patient was superior to that typically observed in CN type II disease. Sequencing revealed compound heterozygous mutations, c.211G>A (p.G71R), c.1470C>T (p.D490D) and a normal homozygous A[TA]6TAA. No similar case has been reported worldwide and, considering the specific clinical features and therapeutic efficacy, a distinct type of CN was suspected. The phenotype of this unusual CN syndrome patient may be associated with the specific genotype.

Acupuncture versus metoclopramide in treatment of postoperative gastroparesis syndrome in abdominal surgical patients: a randomized controlled trial.

BACKGROUND: Postoperative gastroparesis syndrome (PGS) is a common complication after abdominal surgery in patients with primary liver cancer. However, surgeons usually do not have effective treatment for them. OBJECTIVE: To explore the effects of acupuncture applied to Zusanli and other acupoints on PGS in patients after abdominal surgery. DESIGN, SETTING, PARTICIPANTS AND INTERVENTIONS: Sixty-three PGS patients of abdominal surgery, from Eastern Hepatobiliary Surgical Hospital, were randomized into acupuncture group (32 cases) and metoclopramide group (31 cases). The patients in acupuncture group were treated with acupuncture applied to Zusanli and other acupoints once a day, while the patients in metoclopramide group were intramuscularly injected 20 mg metoclopramide three times a day. MAIN OUTCOME MEASURES: Volume of gastric drainage, number of treatment and cure rate in the two groups were measured and evaluated. RESULTS: Acupuncture and metoclopramide could significantly reduce gastric drainage volume. In acupuncture group, the cure rate was 90.6% and the number of treatment was 6.58+/-4.26, while in metoclopramide group, the cure rate and the number of treatment were 32.3% and 10.13+/-3.60 respectively. There were significant differences in gastric drainage volume, cure rate and number of treatment between the two groups (P<0.05, P<0.01). CONCLUSION: Acupuncture is a good treatment for PGS, with fewer treatments, high cure rate and rapid effect.

[The effect of sorphoridine on neuron ultrastructure in CA3 of hippocampus in rats].

OBJECTIVE: To observe the effect of sorphoridine (SR) on electroencephalograph (EEG) and ethological changes as well as neurons ultrastructure alterations in CA3 of hippocampus in rats. METHODS: Tiny electrodes were embedded into hippocampus of male SD rats. The EEG and behavior changes were observed simultaneously and ultrastructure of morphological deformation of neurons in CA3 of hippocampus were observed with electron microscope at 0.5, 1.5, 8 hours after SR were injected intraperitoneally on freely moving rats. RESULTS: There were no epileptiform discharges and seizure activities observed in control group. There was no abnormality seen on neuron in hippocampus of CA3 in control group. While there were epileptiform discharges and convulsions observed simultaneously when SR were administrated at the dose of 55 mg/kg intraperitoneally. 0.5, 1.5, 8 hours after SR, mitochondrion showed swelling cristae and ruptured membrane. Organelle burst and degeneration of synapses were seen with electromicroscope in CA3 of hippocampus ,especially at 1.5 hours after SR administration. CONCLUSION: Sophoridine can induce acute seizure activity on rats and cause mitochondrion ultrastructural damage. The ultrastructural damage of mitochondrion occurs in the early period after SR administration. It indicates that the injury of mitochondria could be critical in neuron damage caused by sorphoridine.

[Relationship between female ages and the theory of five tones correlated with five zang viscera in Huangdi Neijing].

OBJECTIVE: To find out some evidence that may indicate the theory of voice pitch of the five tones being correlated with the five zang viscera in Huangdi Neijing, which was lost 2 000 years. METHODS: Eight-four healthy females were divided into younger group (<34 years old) and older group (> or =34 years old) according to their ages. The pronunciations of these females were examined by sono-frequency analysis facility. RESULTS: The frequency of Jiao tone was much higher than those of the other tones in both groups (P<0.01) and the frequency of Jiao tone increased as aging. The frequency of Zhi tone in the younger group was higher than that in the older group (P<0.05). CONCLUSION: The results of higher frequency of Jiao tone in females is in accordance with the theory put forward by Ye Gui (a famous doctor in Qing Dynasty of China) that the liver is the congenital base of female life. In traditional Chinese medicine, Jiao tone is correlated with the liver, and Zhi tone is correlated with the heart. The high frequency of Zhi tone in younger females implies that regulating the Small Intestine Meridian of Hand-Taiyang and Heart Meridian of Hand-Shaoyin may be beneficial to the health maintenance of younger female.