Hyperoxia combined with the B-cell antagonist rituximab led to intestinal dysbiosis in neonatal mice.

The adverse factors impacting the intestinal microbiota of newborns remain to be elucidated. We put forward a hypothesis that hyperoxia in combination with rituximab exhibits a synergistic effect that interferes with neonatal intestinal microbiota. Six C57BL/6J mice, aged 12 weeks and pregnant 18 days, were purchased. Their pups were breastfed and raised under a 75% oxygen or conventional environment. Low- (20 mg/kg) and high-dose (40 mg/kg) rituximab were intraperitoneally administered. Fecal genomic DNA was extracted and sequenced by a 16S rRNA platform. Severe intestinal dysbiosis in newborns were observed, whereas mild dysbiosis was caused by inducing hyperoxia alone, confirming the synergistic interference of the combination of hyperoxia and B-cell antagonist (rituximab) in neonatal intestinal microbiota disruption. Slight dysbiosis was observed in the intestinal microbiota of dams, indicating their much robust ability to confront hyperoxic conditions. The abundance of Akkermansia muciniphila was significantly and extensively altered in both pups and dams after being subjecting them to hyperoxic conditions with or without rituximab administration. In conclusion, this work demonstrated that the synergistic effect of hyperoxia and rituximab led to severe intestinal dysbiosis in newborns. More studies are recommended to explore the precise regulatory mode between hyperoxia and rituximab in intestinal microbiota.

Electroacupuncture for weight loss by regulating microglial polarization in the arcuate nucleus of the hypothalamus.

Electroacupuncture (EA) has a weight loss effect, but the underlying molecular mechanisms of weight loss with EA have not been fully elucidated. This study aimed to investigate the modulatory effects of EA on the phenotype of hypothalamic microglia in obese mice. A total of 50 male C57BL/6J mice were used in this study. There were three groups in this experiment: The conventional diet group (Chow group), the high-fat diet group (HFD group), and the EA intervention group (HFD + EA group). EA was applied at "Tianshu (ST25)", "Guanyuan (RN4)", "Zusanli (ST36)" and "Zhongwan (RN12)" every day for 10 min. Hematoxylin and eosin (H&E) staining, immunohistochemical staining, and real-time PCR were applied in this study. The results showed that EA intervention was associated with a decrease in body weight, food intake, adipose tissue weight, and adipocyte size. At the same time, EA induced microglia to exhibit an M2 phenotype, representing reduced iNOS/TNF-α and increased Arg-1/IL-10/BDNF, which may be due to the promotion of TREM2 expression. EA also reduced microglia enrichment in the hypothalamic arcuate nucleus and declined TLR4 and IL-6, inhibiting microglia-mediated neuroinflammation. In addition, EA treatment promoted POMC expression, which may be associated with reduced food intake and weight loss in obese mice. This work provides novel evidence of EA against obesity. However, further study is necessary of EA as a therapy for obesity.

Electroacupuncture facilitates M2 macrophage polarization and its potential role in the regulation of inflammatory response.

The underlying mechanism of electroacupuncture (EA) in relieving obesity, anti-inflammation and the interaction with metabolic pathways in obese mice has not been elaborated. The aim of this study was to investigate the regulation of EA on macrophage polarization in obesity tissue of diet-induced obesity mice. Mice were divided in 6 groups: normal control group, model group, EA-7 group, EA-14 group, EA-21 group and EA-28 group. Low-frequency EA was applied at "Tianshu (ST 25)", "Guanyuan (CV 4)", "Zusanli (ST 36)" and "Sanyinjiao (SP 6)" for 10 min. Adipose tissue was assessed with hematoxylin and eosin staining. Adipocytokines and pro-inflammatory factors expression was measured by ELISA. The protein and mRNA levels of macrophage markers were examined by immumohistochemical staining and RT-PCR, respectively. EA treatment was associated with a decrease of adipose tissue and large adipocytes, and an increase of small adipocytes. After EA treatment, the levels of Leptin, Chemerin, TNF-α, F4/80, iNOS, and CD11c decreased obviously in adipose tissue, while IL-4, IL-10 and CD206 levels increased significantly. Besides, TNF-α in spleen tissue was also downregulated, but IL-4 and IL-10 were upregulated. EA prevents weight gain through modulation inflammatory response and macrophage polarization in obese adipose tissues.

Pathological Impact on the Phyllosphere Microbiota of Artemisia argyi by Haze.

The pathological impact of haze upon the phyllosphere microbiota awaits investigation. A moderate degree of haze environment and a clean control were selected in Chengdu, China. Artemisia argyi, a ubiquitously distributed and extensively applied Chinese herb, was also chosen for experiment. Total genome DNA was extracted from leaf samples, and for metagenome sequencing, an Illumina HiSeq 2500 platform was applied. The results showed that the gene numbers of phyllosphere microbiota derived from haze leaves were lower than those of the clean control. The phyllosphere microbiota derived from both haze and clean groups shared the same top ten phyla; the abundances of Proteobacteria, Actinomycetes and Anorthococcuso of the haze group were substantially increased, while Ascomycetes and Basidiomycetes decreased. At the genus level, the abundances of Nocardia, Paracoccus, Marmoricola and Knoelia from haze leaves were markedly increased, while the yeasts were statistically decreased. KEGG retrieval demonstrated that the functional genes were most annotated to metabolism. An interesting find of this work is that the phyllosphere microbiota responsible for the synthesis of primary and secondary metabolites in A. argyi were significantly increased under a haze environment. Relatively enriched genes annotated by eggNOG belong to replication, recombination and repair, and genes classified into the glycoside hydrolase and glycosyltransferase enzymes were significantly increased. In summary, we found that both structure and function of phyllosphere microbiota are globally impacted by haze, while primary and secondary metabolites responsible for haze tolerance were considerably increased. These results suggest an adaptive strategy of plants for tolerating and confronting haze damage.

[Expression and significance of P53 and P21 in nasal NK/T-cell lymphoma].

OBJECTIVE: To investigate the significance of P53 and P21 expressions in nasal NK/T-cell lymphoma (NKTL) and their relationships with the clinical stage, prognosis, proliferation and apoptosis of tumor cells. METHODS: The clinicopathologic and follow-up data was collected from 62 patients with NKTL proven by pathological examination. Sixty-two cases of NKTL were examined for P53, P21 and Ki67 proteins with tissue microarray technique and immunohistochemistry. TUNEL method was used to detect apoptosis (apoptosis index, AD). The proliferation index (PI) was determined by the expression of Ki67 proteins. RESULTS: The positive rates of P53 and P21 protein expression in NKTL were 79.03% and 58.06% respectively. The positive rates of P53 in Ann Arbor stage I, II, III and lV NKTL were 69.57%, 75.00%, 86.67% and 100.00% respectively, while those of P21 were 47.83%, 56.25%, 60.00% and 87.50%. With the progression of tumor, the positive expression rates of P53 and P21 proteins gradually increased. And there were significant differences statistically between the expressions of P53/ P21 and Ann Arbor stage (P < 0.05). The expression of P53 was positively correlated with the expression of P21(r = 0.467, P < 0.05). The prognosis of P53 and P21 positive expression group was worse than that of negative expression group (P < 0.05). The expression of P53 protein was an independent prognostic factor. The intensities of P53 and P21 expressions were positively correlated with PI (r = 0.177, 0.184, P < 0.05), while not correlated with AI (P > 0.05). CONCLUSION: The expressions of P53, P21 and Ki67 proteins are closely related with the pathogenesis and progression of NKTL. Combined detection of P53, P21 and Ki67 could be better to judge the biological behavior of NKTL.

[Expression and significance of p53-related proteins and LMP-1 in nasal NK/T-cell lymphoma].

OBJECTIVE: To investigate the expression of murine double minute 2 (mdm2), p53, p21 and latent membrane protein 1 (LMP-1) in nasal NK/T-cell lymphoma (NKTL) and analyze their relationship with the clinical stage and prognosis. METHODS: The clinicopathological and follow-up data of 62 patients with NKTL proven by pathology were collected. Paraffin-embedded tissue sections were examined for mdm2, p53, p21 and LMP-1 proteins by tissue microarray technique and immunohistochemistry. In situ hybridization was used to detect EBER1/2. RESULTS: The positive expression rates of mdm2, p53, p21 and LMP-1 proteins in NKTL were 61.3%, 79.0%, 58.1% and 48.4%, respectively, and EBER1/2 was 90.3%. The positive expression rates of mdm2 in Ann Arbor stage I, II, III and IV NKTL were 43.5%, 62.5%, 73.3% and 87.5%, respectively; p53 were 69.6%, 75.0%, 86.7% and 100.0%; p21 were 47.8%, 56.3%, 60.0% and 87.5%; while those of LMP-1 were 60.9%, 50.0%, 26.7% and 50.0%, respectively. With the progression of tumor, the positive expression rates of mdm2, p53 and p21 proteins gradually increased. There were statistically significant differences between them (P<0.05). There were statistically positive correlations among those three genes (P<0.05). The prognosis of the positive expression group of these three genes was worse than that of negative expression group (P<0.05). No statistically significant difference was observed between the expression of LMP-1 protein and the clinical stage or prognosis (P>0.05). The expression of p53 protein was an independent prognostic factor. CONCLUSION: The expression of mdm2, p53 and p21 proteins is closely related with the pathogenesis and progression of NKTL. They are good markers for judgement of the biological behavior of NKTL. The expression of p53 protein is an independent prognostic factor. Though no significant relationship was found between the expression of LMP-1 protein and the clinical stage or prognosis, it may play some role in tumor progression.