Microencapsulated Schwann cell transplantation inhibits P2X3 receptor expression in dorsal root ganglia and neuropathic pain

Schwann cell transplantation is a promising method to promote neural repair, and can be used for peripheral nerve protection and myelination. Microcapsule technology largely mitigates immune rejection of transplanted cells. We previously showed that microencapsulated olfactory ensheathing cells can reduce neuropathic pain and we hypothesized that microencapsulated Schwann cells can also inhibit neuropathic pain. Rat Schwann cells were cultured by subculture and then microencapsulated and were tested using a rat chronic constriction injury（CCI） neuropathic pain model. CCI rats were treated with Schwann cells or microencapsulated Schwann cells and were compared with sham and CCI groups. Mechanical withdrawal threshold and thermal withdrawal latency were assessed preoperatively and at 1, 3, 5, 7, 9, 11 and 14 days postoperatively. The expression of P2X3 receptors in L4-5 dorsal root ganglia of the different groups was detected by double-label immunofluorescence on day 14 after surgery. Compared with the chronic constriction injury group, mechanical withdrawal threshold and thermal withdrawal latency were higher, but the expression of P2X3 receptors was remarkably decreased in rats treated with Schwann cells and microencapsulated Schwann cells, especially in the rats transplanted with microencapsulated Schwann cells. The above data show that microencapsulated Schwann cell transplantation inhibits P2X3 receptor expression in L4-5 dorsal root ganglia and neuropathic pain.

A 14-year multi-institutional collaborative study of Chinese pelvic floor surgical procedures related to pelvic organ prolapse

Background:It has been a global trend that increasing complications related to pelvic floor surgeries have been reported over time.The current study aimed to outline the development of Chinese pelvic floor surgeries related to pelvic organ prolapse(POP)over the past 14 years and investigate the potential influence of enhanced monitoring conducted by the Chinese Association of Urogynecology since 2011.Methods:A total of 44,594 women with POP who underwent pelvic floor surgeries between October 1,2004 and September 30,2018 were included from 22 tertiary academic medical centers.The data were reported voluntarily and obtained from a database.We compared the proportion of each procedure in the 7 years before and 7 years after September 30,2011.The data were analyzed by performing Z test(one-sided).Results:The number of different procedures during October 1,2011-September 30,2018 was more than twice that during October 1,2004-September 30,2011.Regarding pelvic floor surgeries related to POP,the rate of synthetic mesh procedures increased from 38.1%(5298/13,906)during October 1,2004-September 30,2011 to 46.0%(14,107/30,688)during October 1,2011-September 30,2018,whereas the rate of non-mesh procedures decreased from 61.9%(8608/13,906)to 54.0%(16,581/30,688)(Z=15.53,P<0.001).Regarding synthetic mesh surgeries related to POP,the rates of transvaginal placement of surgical mesh(TVM)procedures decreased from 94.1%(4983/5298)to 82.2%(11,603/14,107)(Z=20.79,P<0.001),but the rate of laparoscopic sacrocolpopexy(LSC)procedures increased from 5.9%(315/5298)to 17.8%(2504/14,107).Conclusions:The rate of synthetic mesh procedures increased while that of non-mesh procedures decreased significantly.The rate of TVM procedures decreased while the rate of LSC procedures increased significantly.Trial registration number:NCT03620565,https://register.clinicaltrials.gov.

The in ovo injection of methionine improves intestinal cell proliferation and differentiation in chick embryos by activating the JAK2/STAT3 signaling pathway

The intestinal health of chick embryos is vital for their life-long growth,and exogenous nutrition intervention may provide sufficient nutrition for embryonic development.In the present study,we investigated the effect of in ovo injection of L-methionine(L-Met)on the intestinal structure and barrier function of chick embryos.There were 4 groups of treatments:the control(CON)group injected with phosphate-buffered saline(PBS)and the other 3 groups injected with 5,10,and 20 mg L-Met/egg,respectively.The injection was performed on embryonic day 9(E9),and intestinal samples were collected on the day of hatching for analysis.The results showed that,compared with the CON group,the groups administered an in ovo injection of L-Met increased relative weights of the duodenum,jejunum,and ileum(P<0.05).Hematoxylin and eosin(H&E)staining showed that the groups injected with 5,10,and 20 mg L-Met significantly increased villus height and crypt depth(P<0.05).Moreover,in ovo injection of 10 mg L-Met also increased the transepithelial electrical resistance(TEER)of the jejunum(P<0.05).Injection with 10 and 20 mg L-Met increased the expression of the tight junction proteins(ZO-1 and claudin-1)and the fluorescence signal intensity of Ki67 and villin proteins(P<0.05).Further,the protein expression of phospho-Janus kinase 2(p-JAK2)and phospho-signal transducer and activator of transcription 3(p-STAT3)was significantly increased by 10 or 20 mg L-Met injection(P<0.05).In conclusion,the injection of L-Met,especially at a dose of 10 mg,showed beneficial effects on the intestinal integrity of chick embryos due to the activation of the JAK2/STAT3 signaling pathway.Our results may provide new insights for regulating the intestinal development of embryonic chicks and the rapid growth of chicks after hatching.

Heat stress inhibits proliferation, promotes growth, and induces apoptosis in cultured Lantang swine skeletal muscle satellite cells

Proliferation suppression and apoptosis are the prominent characteristics induced by heat stress（HS） in cells, whereas the effects of HS on cell growth（mass accumulation） are unknown. In this study, Lantang swine（an indigenous breed of China） skeletal muscle satellite cells（SCs） were pre-cultured at 37 °C for 24 h. The HS group was subjected to HS at 41 °C, while the control group was maintained at 37 °C. Heat shock protein 70（HSP70） expression and SC size are significantly increased（P〈0.05） by HS, but cell proliferation is suppressed（P〈0.05） and apoptosis is induced（P〈0.05）. HS led to a lower percentage of SCs in the G0/G1 phase（P〈0.05） together with a higher percentage of SCs in the S phase（P〈0.05）. However, the percentage of SCs in the G2/M phase was decreased（P〈0.05） at 48 h but then increased（P〈0.05） at 72 h with HS. In addition, the phosphorylation ratios of protein kinase b（Akt）, ribosomal protein S6 kinase（S6K）, and ribosomal protein S6 were increased（P〈0.05） by HS. Nevertheless, the phosphorylation ratios of the 4E binding protein 1 and the eukaryotic initiation factor-4E were indistinguishable（P〉0.05） from those of the control group. The phosphorylation ratio of the mammalian target of rapamycin（m TOR）（Ser^2448） increased（P〈0.05） within 48 h, and apparent differences were abrogated at 72 h（P〉0.05）. Moreover, cleaved caspase-3 expression was increased at 72 h（P〈0.05）. These findings indicate that HS induces apoptosis and disrupts cell cycle distribution to decrease the number of cells. Additionally, HS can promote SC growth via an activated Akt/m TOR/S6 K signaling pathway.

Growth of embryo and gene expression of nutrient transporters in the small intestine of the domestic pigeon(Columba livia)

The objective of this study was to investigate the relationship between gene expression of nutrient（amino acid, peptide, sodium and proton） transporters in the small intestine and embryonic growth in domestic pigeons（Columba livia）. One hundred and twenty-five fertilized eggs were randomly assigned into five groups and were incubated under optimal conditions（temperature of 38.1 °C and relative humidity of 55%）. Twenty embryos/birds from each group were sacrificed by cervical dislocation on embryonic day（E） 9, 11, 13, 15 and day of hatch（DOH）. The eggs, embryos（without yolk sac）, and organs（head, brain, heart, liver, lungs, kidney, gizzard, small intestine, legs, and thorax） were dissected, cleaned, and weighed. Small intestine samples were collected for RNA isolation. The m RNA abundance of intestinal nutrient transporters was evaluated by real-time reverse transcription-polymerase chain reaction（RT-PCR）. We classified these ten organs into four types according to the changes in relative weight during embryonic development. In addition, the gene expression of nutrient transporters was differentially regulated by embryonic day. The m RNA abundances of b^0,＋AT, EAAT3, y^＋LAT2, Pep T1, LAT4, NHE2, and NHE3 increased linearly with age, whereas m RNA abundances of CAT1, CAT2, LAT1, EAAT2, SNAT1, and SNAT2 were increased to higher levels on E9 or E11 and then decreased to lower levels until DOH. The results of correlation analysis showed that the gene expressions of b^0,＋AT, EAAT3, Pep T1, LAT4, NHE2, NHE3, and y^＋LAT2 had positive correlations with body weight（0.71〈correlation coefficient（CC）〈0.82, P〈0.0001）, while CAT1, CAT2, EAAT2, SNAT1, and SNAT2 had negative correlations with body weight（-0.86〈CC〈-0.64, P〈0.0001）. The gene expressions of b^0,＋AT, EAAT3, LAT4, Pep T1, NHE2, NHE3, and y^＋LAT2 showed positive correlations with intestinal weight（0.80〈CC〈0.91, P〈0.0001）, while CAT1, CAT2, and EAAT2 showed negative correlations with intestinal weight（-0.84〈CC〈-0.67, P〈0.0001）. It was concluded that the differences between growth trajectories of organs and gene expression of nutrient transporters in small intestine were due to their functional and physiological properties, which provided a comprehensive study of amino acid and peptide transporter m RNA in the small intestine during embryonic growth of pigeons.

A report of a new late toxic effect of lenvatinib

To the Editor:Hepatocellular carcinoma(HCC)is the third most lethal malignancy globally.[1]Besides sorafenib,lenvatinib is currently the second approved targeted agent for the first-line treatment of HCC in 2018.Lenvatinib is an oral multikinase inhibitor that targets vascular endothelial growth factor(VEGF)receptors 1 to 3,fibroblast growth factor receptors 1 to 4,platelet-derived growth factor receptor a,RET,and KIT.[2]Patients who received lenvatinib experienced diarrhoea,and alope and more instances of hypertension,proteinuria,and hypothyroidism.Here,we report two patients that developed irreversible pancreatic atrophy as a novel adverse event of lenvatinib.