Xiaotan Sanjie decoction attenuates tumor angiogenesis by manipulating Notch-1-regulated proliferation of gastric cancer stem-like cells

AIM: To determine the underlying mechanisms of action and influence of Xiaotan Sanjie(XTSJ) decoction on gastric cancer stem-like cells(GCSCs). METHODS: The gastric cancer cell line MKN-45 line was selected and sorted by FACS using the cancer stem cell marker CD44; the stemness of these cells was checked in our previous study. In an in vitro study, the expression of Notch-1, Hes1, Vascular endothelial growth factor(VEGF), and Ki-67 in both CD44-positive gastric cancer stem-like cells(GCSCs) and CD44-negative cells was measured by Western blot. The effect of XTSJ serum on cell viability and on the above markers was measured by MTT assay and Western blot, respectively. In an in vivo study, the ability to induce angiogenesis and maintenance of GCSCs in CD44-positive-MKN-45- and CD44-negative-engrafted mice were detected by immunohistochemical staining using markers for CD34 and CD44, respectively. The role of XTSJ decoction in regulating the expression of Notch-1, Hes1, VEGF and Ki-67 was measured by Western blot and real-time polymerase chain reaction.RESULTS: CD44+ GCSCs showed more cell proliferation and VEGF secretion than CD44-negative cells in vitro, which were accompanied by the high expression of Notch-1 and Hes1 and positively associated with tumor growth(GCSCs vs CD44-negative cells, 2.72 ± 0.25 vs 1.46 ± 0.16, P < 0.05) and microvessel density(MVD)(GCSCs vs CD44-negative cells, 8.15 ± 0.42 vs 3.83 ± 0.49, P < 0.001) in vivo. XTSJ decoction inhibited the viability of both cell types in a dose-dependent manner in vitro. Specifically, a significant difference in the medium-(82.87% ± 6.53%) and high-dose XTSJ groups(77.43% ± 7.34%) was detected at 24 h in the CD44+ GCSCs group compared with the saline group(95.42% ± 5.76%) and the low-dose XTSJ group(90.74% ± 6.57%)(P < 0.05). However, the efficacy of XTSJ decoction was reduced in the CD44- groups; significant differences were only detected in the high-dose XTSJ group at 48 h(78.57% ± 6.94%) and 72 h(72.12% ± 7.68%) when compared with the other CD44- groups(P < 0.05). Notably, these differences were highly consistent with the Notch-1, Hes1, VEGF and Ki-67 expression in these cells. Similarly, in vivo, XTSJ decoction inhibited tumor growth in a dose-dependent manner. A significant difference was observed in the medium(1.76 ± 0.15) and high-dose XTSJ(1.33 ± 0.081) groups compared with the GCSCs control group(2.72 ± 0.25) and the low-dose XTSJ group(2.51 ± 0.25)(P < 0.05). We also detected a remarkable decrease of MVD in the medium-(7.10 ± 0.60) and high-dose XTSJ(5.99 ± 0.47) groups compared with the GCSC control group(8.15 ± 0.42) and the low-dose XTSJ group(8.14 ± 0.46)(P < 0.05). Additionally, CD44 expression was decreased in these groups [medium-(4.43 ± 0.45) and high-dose XTSJ groups(3.56 ± 0.31) vs the GCSC control(5.96 ± 0.46) and low dose XTSJ groups(5.91 ± 0.38)](P < 0.05). The significant differences in Notch-1, Hes1, VEGF and Ki-67 expression highly mirrored the results of XTSJ decoction in inhibiting tumor growth, MVD and CD44 expression.CONCLUSION: Notch-1 may play an important role in regulating the proliferation of GCSCs; XTSJ decoction could attenuate tumor angiogenesis, at least partially, by inhibiting Notch-1.

Xiaotan Tongfu granules contribute to the prevention of stress ulcers

AIM:To investigate the efficacy and potential mechanism of Xiaotan Tongfu granules(XTTF)in stress ulcers.METHODS:One hundred sixty rats were randomly divided into 4 groups(n=10)as follows:the model group(MP group),the control group(CP group),the ranitidine group(RP group)and the XTTF granule group(XP group).Rats in the MP group received no drugs,rats in the CP group received 0.2 mL of a 0.9%sodium chloride solution via oral gavage,and rats in the RP and XP groups received the same volume of ranitidine(50 mg/kg)or XTTF granule(4.9 g/kg).The cold-restraint stress model was applied to induce stress ulcers after 7 consecutive days of drug administration.Afterwards,rats were sacrificed at 0,3,6 and24 h.Gastric pH was measured by a precise pH meter;gastric emptying rate(GER)was measured by using a methylcellulose test meal;myeloperoxidase activity(MPO),macrophage migration inhibitory factor(MIF),proliferating cell nuclear antigen(PCNA),and heat shock protein 70(HSP70)were measured by immunohistochemical staining;and mucosal cell apoptosis was measured by transferase dUTP nick end labeling.RESULTS:In the cold-restraint stress model,the development of stress ulcers peaked at 3 h and basically regressed after 24 h.Gastric lesions were significantly different in the RP and XP groups at each time point.Interestingly,although this index was much lower in the RP group than in the XP group immediately following stress induction(7.00±1.10 vs 10.00±1.79,P<0.05.Concerning gastric pH,between the RP and XP groups,we detected a statistically significant difference immediately after stress induction(0 h:4.56±0.47 vs 3.34±0.28,P<0.05)but not at any of the subsequent time points.For GER,compared to the RP group,GER was remarkably elevated in the XP group because a statistically significant difference was detected(3 h:46.84±2.70 vs 61.16±5.12,P<0.05;6 h:60.96±6.71 vs 73.41±6.16,P<0.05;24 h:77.47±3.17 vs 91.31±4.34,P<0.05).With respect to MPO and MIF,comparisons between the RP and XP groups revealed statistically significant differences at 3 h(MPO:18.94±1.20 vs 13.51±0.89,P<0.05;MIF:150.67±9.85 vs 122.17±5.67,P<0.05)and 6 h(MPO:13.22±1.54 vs 8.83±0.65,P<0.05;MIF:135.50±9.46 vs 109.83±6.40,P<0.05).With regard to HSP70,HSP70 expression was significantly increased in the RP and XP groups at 3 and 6 h compared to the MP and CP groups.In addition,comparing the RP and XP groups also showed statistically significant differences at 3 and 6 h.The expression of PCNA was higher in the RP and XP groups 3 h after stress induction.Between these two groups,small but statistically significant differences were observed at all of the time points(3 h:69.50±21.52 vs 79.33±15.68,P<0.05;6 h:107.83±4.40 vs 121.33±5.71,P<0.05;24 h:125.33±5.65 vs 128.50±14.49,P<0.05)except 0 h.With regard to apoptosis,the apoptotic activity in the RP and XP groups was significantly different from that in the MP and CP groups.The XP group exhibited a higher inhibition of cell apoptosis than the RP group at3 h(232.58±24.51 vs 174.46±10.35,P<0.05)and6 h(164.74±18.31 vs 117.71±12.08,P<0.05).CONCLUSION:The Xiaotan Tongfu granule was demonstrated to be similar to ranitidine in preventing stress ulcers.It exhibited multiple underlying mechanisms and deserves further study.

Secondary acute promyelocytic leukemia following chemotherapy for gastric cancer: A case report

Therapy-related acute myeloid leukemia(t-AML) refers to a heterogeneous group of myeloid neoplasms that develop in patients following extensive exposure to either cytotoxic agents or radiation.The development of t-AML has been reported following treatment of cancers ranging from hematological malignancies to solid tumors; however, to our knowledge, t-AML has never been reported following treatment of gastric cancer.In this study, we report the development of t-acute promyelocytic leukemia in a cT 4N1M0 gastric cancer patient after an approximate 44 mo latency period following treatment with 4 cycles of oxaliplatin(OXP)(85 mg/m2 on day 1) plus capecitabine(1250 mg/m2 orally twice daily on days 1-14) in combination with recombinant human granulocyte-colony stimulating factor treatment.Karyotype analysis of the patient revealed 46,XY,t(15;17)(q22;q21)[15]/46,idem,-9,+add(9)(p22)[2]/46,XY[3], which, according to previous studies, includes some "favorable" genetic abnormalities.The patient was then treated with all-trans retinoic acid(ATRA, 25 mg/m2/d) plus arsenic trioxide(ATO, 10 mg/d) and attained complete remission.Our case illuminated the role of certain cytotoxic agents in the induction of t-AML following gastric cancer treatment.We recommend instituting a mandatory additional evaluation for patients undergoing these therapies in the future.

Millimeter-sized few-layer graphene sheets with aligned channels for fast lithium-ion charging kinetics

Assembly of the top-down graphene units mostly results in 3D porous structure with randomly organized pores.The direct bottom-up synthesis of macroscopic 2D graphene sheets with organized pores are long sought in materials chemistry field,but rarely achieved.Herein,we present a self-catalysisassisted bottom-up route usingL-glutamic acid and iron chloride as starting materials for the fabrication of the millimeter-sized few-layer graphene sheets with aligned porous channels parallel to the 2D direction.The amino-and carboxyl-functional groups inL-glutamic acid can coordinate with iron cations,thus allowing an atomic dispersion of iron cations.The pyrolysis thus initiated the growth of graphene catalyzed by in-situ generated iron nanoparticles,and a dynamic flow of iron nanoparticles eventually led to the formation of millimeter-sized few-layer graphene sheets with aligned channels(60-85 nm in diameter).Used as anodes in lithium-ion batteries,these graphene sheets showed a good rate capability(142 m A h g^(-1) at 2 A g^(-1))and high capacity retention of 93%at 2 A g^(-1) after 1200 cycles.Kinetic analysis revealed that lithium ions storage was dominated by diffusion behavior and capacitive behavior together,in that graphene sheets with aligned channels could accelerate electron transfer and shorten lithium ions transport pathway.This work provides a novel approach to prepare unique porous graphene materials with specific structure for energy storage.

Influence of different high pressure die casting processes on 3D porosity distribution of Mg-3.0Nd-0.3Zn-0.6Zr alloy

3D reconstruction was adopted to characterize the microstructural morphologies of Mg-3.0Nd-0.3Zn-0.6Zr alloy castings produced by high pressure die casting(HPDC)processes with different parameters,including low slow-shot speed,solidification pressurization and fast slow-shot speed.At low slow-shot speeds of 0.1 m·s^(-1),0.2 m·s^(-1) and 0.3 m·s^(-1),the porosity is concentrated in the center of the castings with one spiral staggered shape along the liquid flow direction.The porosity volume simultaneously decreases with the reduction of quantity and size of externally solidified crystals(ESCs),while the shrinkage pores become more and more dispersed with the increasing low slow-shot speed.Pressurization not only reduces the porosity volume due to the improvement of feeding ability,but also transformes the center gathered porosity into one layer-by-layer distribution form.Accompanied with the increasing fast slow-shot speed,the central porosity dramatically decreases and transforms into a large-scale spiral staggered shape along the liquid flow direction.However,the porosity is much more dispersed when the speed is increased from 2 m·s^(-1) to 3 m·s^(-1).

Using the internet search data to investigate symptom characteristics of COVID-19: A big data study

Objective:Analyzing the symptom characteristics of Coronavirus Disease 2019(COVID-19)to improve control and prevention.Methods:Using the Baidu Index Platform(http://index.baidu.com)and the website of Chinese Center for Disease Control and Prevention as data resources to obtain the search volume(SV)of keywords for symptoms associated with COVID-19 from January 1 to February 20 in each year from 2017 to 2020 and the epidemic data in Hubei province and the other top 9 impacted provinces in China.Data of 2020 were compared with those of the previous three years.Data of Hubei province were compared with those of the other 9 provinces.The differences and characteristics of the SV of COVID-19-related symptoms,and the correlations between the SV of COVID-19 and the number of newly confirmed/suspected cases were analyzed.The lag ef-fects were discussed.Results:Comparing the SV from January 1,2020 to February 20,2020 with those for the same period of the previous three years,Hubei’s SV for cough,fever,diarrhea,chest tightness,dys-pnea,and other symptoms were significantly increased.The total SV of lower respiratory symptoms was significantly higher than that of upper respiratory symptoms(P<0.001).The SV of COVID-19 in Hubei province was significantly correlated with the number of newly confirmed/suspected cases(rconfirmed Z 0.723,rsuspected Z 0.863,both p<0.001).The results of the distributed lag model suggested that the patients who searched relevant symptoms on the Internet may begin to see doctors in 2e3 days later and be confirmed in 3e4 days later.Conclusion:The total SV of lower respiratory symptoms was higher than that of upper respira-tory symptoms,and the SV of diarrhea also increased significantly.It warned us to pay atten-tion to not only the symptoms of the lower respiratory tract but also the gastrointestinal symptoms,especially diarrhea in patients with COVID-19.Internet search behavior had a pos-itive correlation with the number of newly confirmed/suspected cases,suggesting that big data has an important role in the early warning of infectious diseases.