[Establishment of Patient-Derived Xenograft (PDX) Zebrafish Model of Multiple Myeloma and Its Application in Drug Screening].

OBJECTIVE: To establish a MM patient-derived tumor xenograft model (MM-PDX) in zebrafish, and to evaluate the anti-myeloma activity of indirubin-3'-monoxime(I3MO) using this model. METHODS: Zebrafish embryos 2 days after fertilization were transplanted with fluorescence labeled myeloma primary tumor cells, the survival of primary tumor cells in zebrafish was observed at 0,16 and 24 hours after cell injection. The zebrafish embryos after tumor cell transplantation were randomly divided into control group, BTZ treatment and I3MO treatment group. Before and 24 hours after treatment with BTZ and I3MO, the positive area with calcein or Dil in zebrafish were observed under fluorescence microscope to reflect the survival of tumor cells, and it was verified. RESULTS: MM patient derived tumor cells survived in zebrafish. The construction of MM-PDX was successful. Compared with control group, the fluo- rescence area of the BTZ and I3MO treatment groups in zebrafish were significantly decreased(P<0.05), and BTZ and I3MO significantly inhibited the survival of MM cells in zebrafish. CONCLUSION: MM-PDX model was successfully established. Zebrafish model derived from tumor cells of MM patients can be used as a tool for drug screening of MM.

Core-shell structured hollow copper sulfide@metal-organic framework for magnetic resonance imaging guided photothermal therapy in second near-infrared biological window.

Multifunctional core-shell hybrids formed by integration of metal-organic framework (MOF) and functional materials have attracted extensive attention as promising theranostic nanoplatforms due to their combined novel properties and enhanced therapeutic efficacy. Recently, the second near-infrared (NIR-II, 1000-1700 nm) laser-induced photothermal therapy (PTT) as compared to the NIR-I(700-950 nm) laser-induced PTT has displayed improved therapeutic effects owing to its merits that include deeper tissue penetration and increased maximum permissible exposure. Herein, a novel core-shell hollow copper sulfide@metal-organic framework (HCuS@MIL-100) has been successfully fabricated by a layer-by-layer technique for the first time and their collective theranostic effects are investigated in vitro and in vivo. In this platform, the inner HCuS was applied as the NIR-II photothermal agent with excellent NIR-II absorption feature, leading to impressive photothermal effects under irradiation by 1064 nm light. With MIL-100 as the shell, HCuS@MIL-100 not only displayed optimal biocompatibility but also presented superior T2 magnetic resonance imaging (MRI) ability. In the current study multifunctional hollow core-shell HCuS@MIL-100 are fabricated for the MRI-guided PTT. This study also offers a facile and effective strategy for the development of novel theranostic platforms with high efficiency through the integration of MOFs and functional materials.

Molecular mechanisms and therapeutic applications of huaier in breast cancer treatment.

Breast cancer is one of the most common female malignant tumors today and represents a serious health risk for women. Although the survival rate and quality of life of patients with breast cancer are improving with the continuous development of medical technology, metastasis, recurrence, and drug resistance of breast cancer remain a significant problem. Huaier, a traditional Chinese medicine (TCM) fungus, is a type of Sophora embolism fungus growing on old Sophora stems. The polysaccharides of Trametes robiniophila Murr (PS-T) are the main active ingredient of Huaier. There is increasing evidence that Huaier has great potential in breast cancer treatment, and its anti-cancer mechanism may be related to a variety of biological activities, such as the inhibition of cell proliferation, metastasis, tumor angiogenesis, the promotion of cancer cell death, and regulation of tumor-specific immunity. There is growing evidence that Huaier may be effective in the clinical treatment of breast cancer. This review systematically summarizes the basic and clinical studies on the use of Huaier in the treatment of breast cancer, providing useful information to guide the clinical application of Huaier and future clinical studies.

Delivery of acetamiprid to tea leaves enabled by porous silica nanoparticles: efficiency, distribution and metabolism of acetamiprid in tea plants.

BACKGROUND: Pesticide residue and its poor utilization remains problematic in agricultural development. To address the issue, a nano-pesticide has been developed by incorporating pesticide acetamiprid in porous silica nanoparticles. RESULTS: This nano-pesticide had an acetamiprid loading content of 354.01 mg g-1. Testing LC50 value against tea aphids of the commercial preparation was three times that of the nano-pesticide. In tea seedlings (Camellia sinensis L.), acetamiprid was transported upward from the stem to the young leaves. On day 30, the average retained concentrations in tea leaves treated with the commercial preparation were about 1.3 times of that in the nano-pesticide preparation. The residual concentrations of dimethyl-acetamiprid in leaves for plants treated with the commercial preparation were about 1.1 times of that in the nano-pesticide preparation. Untargeted metabolomics of by LC-MS on the young leaves of tea seedlings under nano-pesticide and commercial pesticide treatments showed significant numbers of differentially expressed metabolites (P < 0.05 and VIP > 1). Between the nano-pesticide treatment group and the commercial preparation treatment group there were 196 differentially expressed metabolites 2 h after treatment, 200 (7th day), 207 (21st day), and 201 (30th day) in negative ion mode, and 294 (2nd h), 356 (7th day), and 286 (30th day) in positive ion mode. Preliminary identification showed that the major differentially expressed metabolites were glutamic acid, salicylic acid, p-coumaric acid, ribonic acid, glutamine, naringenin diglucoside, sanguiin H4, PG (34:2) and epiafzelechin. CONCLUSIONS: This work demonstrated that our nano-pesticide outperformed the conventional pesticide acetamiprid in terms of insecticidal activity and pesticide residue, and the absorption, transportation and metabolism of nano-pesticide in tea plant were different, which pave a new pathway for pest control in agricultural sector.

Clinical study on acupuncture plus auricular point sticking for tension-type headache / 针灸推拿医学（英文版）

Objective: To observe the clinical efficacy of acupuncture plus auricular point sticking for tension-type headache (TTH). Methods: A total of 90 TTH patients were divided into an acupuncture group, an auricular point sticking group and an observation group by random number table method, with 30 cases in each group. Patients in the observation group received acupuncture plus auricular point sticking for treatment, while those in the acupuncture group only received acupuncture and those in the auricular point sticking group only received auricular point sticking for treatment. The headache attack frequency and the scores of visual analog scale (VAS), self-rating anxiety scale (SAS) and self-rating depression scale (SDS) were observed before treatment, after treatment and 3 months after treatment. The clinical efficacy was evaluated at the follow-up of 3 months after treatment. Results: At follow-up, there were significant differences in clinical efficacy among the three groups (P<0.01 or P<0.05), and the clinical efficacy ranking from high to low was the observation group, the acupuncture group and the auricular point sticking group. After treatment and at follow-up, the VAS score, headache attack frequency, SAS and SDS scores in the three groups were significantly lower than those before treatment (all P<0.01). The above four results in the observation group were lower than those in the acupuncture group and the auricular point sticking group at the same time point (all P<0.01); VAS score in the acupuncture group was lower than that in the auricular point sticking group (both P<0.05). At follow-up, the headache frequency in the acupuncture group was lower than that in the auricular point sticking group (P<0.05). Conclusion: Either using acupuncture and auricular point sticking together or separately can reduce the headache degree of TTH patients, reduce the number of headache attacks, and relieve anxiety and depression. The efficacy of acupuncture plus auricular point sticking is most significant.

Interaction Effects between Doxorubicin and Hernandezine on the Pharmacokinetics by Liquid Chromatography Coupled with Mass Spectrometry.

Doxorubicin (DOX) is an effective anti-tumor drug widely used in clinics. Hernandezine (HER), isolated from a Chinese medicinal herb, has a selective inhibitory effect on DOX multidrug resistance, making DOX more effective in treating cancer. The aim of this study was to investigate the effect of the interaction of HER and DOX on pharmacokinetics. Male Sparague-Dawley rats were randomly divided into three groups: a single DOX group, a single HER group, and a combination group. Plasma concentrations of DOX and HER were determined by the LC-MS/MS method at specified time points after administration, and the main pharmacokinetic parameters were estimated. The results showed that there were significant differences in the Cmax and AUC0-∞ of DOX in the single drug group and combined drug group, indicating that HER could improve the absorption of DOX. However, DOX in combination, in turn, reduced the free drug concentration of HER, possibly because DOX enhanced the HER drug-protein binding effect. The results could be used as clinical guidance for DOX and HER to avoid adverse reactions.

Nicotinamide induces liver regeneration and improves liver function by activating SIRT1.

Nicotinamide (Nam) has recently been characterized as an agent for tissue regeneration due to the observed pro­proliferation effects. However, the effect of Nam on liver regeneration remains undetermined. In the present study, the potency of Nam as a regimen to promote liver regeneration and restore liver function was evaluated following partial hepatectomy (PH) on C57BL/6 mice. Ki­67 immunohistochemical and cell cycle analyses demonstrated that exogenous Nam supplementation promoted the proliferation of hepatocytes and accelerated the recovery of liver tissue. The addition of Nam protected liver function following PH, as evidenced by hematoxylin and eosin staining of liver tissue morphology and measurement of serum liver injury markers. Notably, immunoblotting results revealed that the expression and activity of NAD­dependent protein deacetylase sirtuin­1 (SIRT1) were significantly upregulated following treatment with Nam, suggesting that Nam may promote liver regeneration through activation of SIRT1. The present study demonstrated that Nam regulated the process of liver regeneration and improved liver function by activating SIRT1, suggesting that Nam has the potency to be used for promoting liver regeneration following surgical resection.

Traditional Chinese medicine as targeted treatment for epithelial-mesenchymal transition-induced cancer progression.

The epithelial-mesenchymal transition (EMT) program, which loosens cell-cell adhesion complexes, endows cells with enhanced migratory and invasive properties. Furthermore, this process facilitates both the development of drug resistance and immunosuppression by tumor cells, which preclude the successful treatment of cancer. Recent research has demonstrated that many signaling pathways are involved in EMT progression. In addition, cancer stem cells (CSCs), vasculogenic mimicry (VM) and the tumor-related immune microenvironment all play important roles in tumor formation. However, there are few reports on the relationships between EMT and these factors. In addition, in recent years, traditional Chinese medicine (TCM) has developed a unique system for treating cancer. In this review, we summarize the crucial signaling pathways associated with the EMT process in cancer patients and discuss the interconnections between EMT and other molecular factors (such as CSCs, VM, and the tumor-related immune microenvironment). We attempt to identify common regulators that might be potential therapeutic targets to thereby optimize tumor treatment. In addition, we outline recent research on TCM approaches that target EMT and thereby provide a foundation for further research on the exact mechanisms by which TCMs affect EMT in cancer.

Fumarate-based metal-organic frameworks as a new platform for highly selective removal of fluoride from brick tea.

Adsorption and removal of fluoride from brick tea is very important but challenging. In this work, two fumarate-based metal-organic frameworks (MOFs) were synthesized for the selective removal of fluoride from brick tea infusion. MOFs were examined for adsorption time, effect of dose, and uptake capacity at different initial concentrations and temperatures. Remarkably, over 80% fluoride removal was achieved by MOF-801 within 5 min at room temperature, while no significant adsorption occurred for the catechins and caffeine in the brick tea infusion. Further, with the use of the Langmuir equation, the maximum fluoride uptake capacity for the nontoxic calcium fumarate (CaFu) MOF was calculated to be as high as 166.11 mg g-1 at 373 K. As observed from FTIR, EDX and XPS results, hydroxyl group in MOFs were substituted by fluoride. This work demonstrates that the novel fumarate-based MOFs are promising materials for the selective removal of fluoride from brick tea infusion.

Cost-effectiveness analysis of transcatheter arterial chemoembolization with or without sorafenib for the treatment of unresectable hepatocellular carcinoma.

BACKGROUND: Transcatheter arterial chemoembolization (TACE) and TACE in combination with sorafenib (TACE-sorafenib) have shown a significant survival benefit for the treatment of unresectable hepatocellular carcinoma (HCC). Adopting either as a first-line therapy carries major cost and resource implications. The objective of this study was to estimate the relative cost-effectiveness of TACE against TACE-sorafenib for unresectable HCC using a decision analytic model. METHODS: A Markov cohort model was developed to compare TACE and TACE-sorafenib. Transition probabilities and utilities were obtained from systematic literature reviews, and costs were obtained from West China Hospital, Sichuan University, China. Survival benefits were reported in quality-adjusted life-years (QALYs). The incremental cost-effectiveness ratio (ICER) was calculated. Sensitive analysis was performed by varying potentially modifiable parameters of the model. RESULTS: The base-case analysis showed that TACE cost $26 951 and yielded survival of 0.71 QALYs, and TACE-sorafenib cost $44 542 and yielded survival of 1.02 QALYs in the entire treatment. The ICER of TACE-sorafenib versus TACE was $56 745 per QALY gained, which was above threshold for cost-effectiveness in China. Sensitivity analysis revealed that the major driver of ICER was the cost post TACE-sorafenib therapy with stable state. CONCLUSION: TACE is a more cost-effective strategy than TACE-sorafenib for the treatment of unresectable HCC.

Highly selective defluoridation of brick tea infusion by tea waste supported aluminum oxides.

BACKGROUND: Brick tea usually contains very high fluoride, which may affect human health. Biosorbents have received much attention for selective removal of fluoride because of low cost, environmental friendliness, and relative safeness. RESULTS: In the present study, a highly selective fluoride tea waste based biosorbent, namely, aluminum (Al) oxide decorated tea waste (Tea-Al), was successfully prepared. The Tea-Al biosorbent was characterized by energy-dispersive spectrometry, Fourier transform infrared spectroscopy, powder X-ray diffraction and X-ray photoelectron spectroscopic analysis. The Tea-Al sample exhibited remarkably selective adsorption for fluoride (52.90%), but a weaker adsorption for other major constituents of brick tea infusion, such as catechins, polyphenols and caffeine, under the same conditions. Fluoride adsorption by Tea-Al for different times obeyed the surface reaction and adsorption isotherms fit the Freundlich model. In addition, the fluoride adsorption mechanism appeared to be an ion exchange between hydroxyl and fluoride ions. CONCLUSION: Results from this study demonstrated that Tea-Al is a promising biosorbent useful for the removal of fluoride in brick tea infusion. © 2016 Society of Chemical Industry.

Brucine inhibits bone metastasis of breast cancer cells by suppressing Jagged1/Notch1 signaling pathways.

OBJECTIVE: To examine the effects of brucine on the invasion, migration and bone resorption of receptor activator of nuclear factor-kappa B ligand (RANKL)-induced osteoclastogenesis. METHODS: The osteoclastogenesis model was builded by co-culturing human breast tumor MDA-MB-231 and mouse RAW264.7 macrophages cells. RANKL (50 ng/mL) and macrophage-colony stimulating factor (50 ng/mL) were added to this system, followed by treatment with brucine (0.02, 0.04 and 0.08 mmol/L), or 10 µmol/L zoledronic acid as positive control. The migration and bone resorption were measured by transwell assay and in vitro bone resorption assay. The protein expressions of Jagged1 and Notch1 were investigated by Western blot. The expressions of transforming growth factor-ß1 (TGF-ß1), nuclear factor-kappa B (NF-κB) and Hes1 were determined by enzyme-linked immunosorbent assay. RESULTS: Compared with the model group, brucine led to a dose-dependent decrease on migration of MDA-MB-231 cells, inhibited RANKL-induced osteoclastogenesis and bone resorption of RAW264.7 cells (P<0.01). Furthermore, brucine decreased the protein levels of Jagged1 and Notch1 in MDA-MB-231 cells and RAW264.7 cells co-cultured system as well as the expressions of TGF-ß1, NF-κB and Hes1 (P<0.05 or P<0.01). CONCLUSION: Brucine may inhibit osteoclastogenesis by suppressing Jagged1/Notch1 signaling pathways.

Clinical Observations on Qin’s Scalp Eight-needle Acupuncture for the Treatment of Cancer Pain / 上海针灸杂志

Objective To compare the clinical efficacies of Qin’s scalp eight-needle acupuncture versus conventional scalp acupuncture in treating cancer pain. Method Sixty cancer pain patients with clinically or pathologically diagnosed malignant tumors were allocated, using a random number table, to a treatment (Qin’s scalp eight-needle acupuncture) group of 30 cases and a control (conventional scalp acupuncture) group of 30 cases. The treatment group received Qin’s scalp eight-needle acupuncture at selected points every other day and the control group, conventional scalp acupuncture every other day. One course of treatment consisted of 10 days. Result Cancer pain was relieved, analgesic dosage decreased, adverse reactions to analgesics reduced and quality of life raised significantly in the treatment group compared with the control group. Conclusion Qin’s scalp eight-needle acupuncture is effective in treating cancer pain.

Molecular cloning and antibacterial activity of hepcidin from Chinese rare minnow (Gobiocypris rarus)

Background Hepcidins, a kind of cysteine-rich antimicrobial peptides, play important roles in host immunological processes and iron regulation, which have been identified from several fish species. The rare minnow (Gobiocypris rarus), an endemic cyprinid fish in China, has been used extensively as model animal in laboratory. However, little is known about its hepcidin. Here, we report the cloning and characterization of a hepcidin gene from the liver of Chinese rare minnow. Results The full-length cDNA of rare minnow hepcidin is 662 bp, which contains an ORF of 273 bp encoding a prepropeptide of 90 amino acid residues. The predicted prepropeptide contains three domains: a signal peptide of 24 amino acids, a prodomain of 41 amino acids, and a mature peptide of 25 amino acids. Sequence alignment showed eight conserved cysteine residues in the mature peptide, which formed four disulfide bonds in spatial structure. The deduced structure of mature peptide showed a high degree of homology to the human hepcidin. Phylogenetic analysis showed that it had a close relationship with zebrafish hepcidin, and clustered in a clade with these from Cyprinidae. Synthetic peptide of rare minnow hepcidin could inhibit the growth of Gram positive bacterium Staphylococcus aureus and Gram negative bacteria Escherichia coli and Aeromonas hydrophila. Conclusion These results suggested that rare minnow hepcidin had typical structure of hepcidins and antibacterial activity. It could participate in innate immune response as an antibacterial agent and be used as antibiotic substance.

Protein kinase A-mediated cardioprotection of Tongxinluo relates to the inhibition of myocardial inflammation, apoptosis, and edema in reperfused swine hearts.

BACKGROUND: Our previous studies have demonstrated that Tongxinluo (TXL), a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A (PKA)-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis. METHODS: In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL (0.05 g/kg, gavaged one hour prior to ischemia), and TXL + H-89 (a PKA inhibitor, intravenously and continuously infused at 1.0 µg/kg per minute) groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein (p-CREB) (Ser(133)), tumor necrosis factor α (TNF-α), P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis. RESULTS: TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% (P < 0.05). TXL pretreatment increased the PKA activity and the expression of Ser(133) p-CREB in the reflow and no-reflow myocardium (P < 0.05). TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-α and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL. CONCLUSION: PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.

Protein kinase A-mediated cardioprotection of Tongxinluo relates to the inhibition of myocardial inflammation, apoptosis, and edema in reperfused swine hearts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Our previous studies have demonstrated that Tongxinluo (TXL), a traditional Chinese medicine, can protect hearts against no-reflow and reperfusion injury in a protein kinase A (PKA)-dependent manner. The present study was to investigate whether the PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis.</p><p><b>METHODS</b>In a 90-minute ischemia and 3-hour reperfusion model, minipigs were randomly assigned to sham, control, TXL (0.05 g/kg, gavaged one hour prior to ischemia), and TXL + H-89 (a PKA inhibitor, intravenously and continuously infused at 1.0 µg/kg per minute) groups. Myocardial no-reflow, necrosis, edema, and apoptosis were determined by pathological and histological studies. Myocardial activity of PKA and myeloperoxidase was measured by colorimetric method. The expression of PKA, phosphorylated cAMP response element-binding protein (p-CREB) (Ser(133)), tumor necrosis factor α (TNF-α), P-selectin, apoptotic proteins, and aquaporins was detected by Western blotting analysis.</p><p><b>RESULTS</b>TXL decreased the no-reflow area by 37.4% and reduced the infarct size by 27.0% (P < 0.05). TXL pretreatment increased the PKA activity and the expression of Ser(133) p-CREB in the reflow and no-reflow myocardium (P < 0.05). TXL inhibited the ischemia-reperfusion-induced elevation of myeloperoxidase activities and the expression of TNF-α and P-selectin, reduced myocardial edema in the left ventricle and the reflow and no-reflow areas and the expression of aquaporin-4, -8, and -9, and decreased myocytes apoptosis by regulation of apoptotic protein expression in the reflow and no-reflow myocardium. However, addition of the PKA inhibitor H-89 counteracted these beneficial effects of TXL.</p><p><b>CONCLUSION</b>PKA-mediated cardioprotection of TXL against no-reflow and reperfusion injury relates to the inhibition of myocardial inflammation, edema, and apoptosis in the reflow and no-reflow myocardium.</p>

Herbal medicine in the treatment of ulcerative colitis.

Ulcerative colitis (UC) is a refractory, chronic, and nonspecific disease occurred usually in the rectum and the entire colon. The etiopathology is probably related to dysregulation of the mucosal immune response toward the resident bacterial flora together with genetic and environmental factors. Several types of medications are used to control the inflammation or reduce symptoms. Herbal medicine includes a wide range of practices and therapies outside the realms of conventional Western medicine. However, there are limited controlled evidences indicating the efficacy of traditional Chinese medicines, such as aloe vera gel, wheat grass juice, Boswellia serrata, and bovine colostrum enemas in the treatment of UC. Although herbal medicines are not devoid of risk, they could still be safer than synthetic drugs. The potential benefits of herbal medicine could lie in their high acceptance by patients, efficacy, relative safety, and relatively low cost. Patients worldwide seem to have adopted herbal medicine in a major way, and the efficacy of herbal medicine has been tested in hundreds of clinical trials in the management of UC. The evidences on herbal medicine are incomplete, complex, and confusing, and certainly associated with both risks and benefits. There is a need for further controlled clinical trials of the potential efficacy of herbal medicine approaches in the treatment of UC, together with enhanced legislation to maximize their quality and safety.

Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts.

BACKGROUND: Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion. METHODS: Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint. RESULTS: At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL. CONCLUSIONS: Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.

Effects of Tongxinluo-facilitated cellular cardiomyoplasty with autologous bone marrow-mesenchymal stem cells on postinfarct swine hearts / 中华医学杂志(英文版)

<p><b>BACKGROUND</b>Treatment of ischemic heart disease remains an important challenge, though there have been enormous progresses in cardiovascular therapeutics. This study was conducted to evaluate whether Tongxinluo (TXL) treatment around the transplantation of mesenchymal stem cells (MSCs) can improve survival and subsequent activities of implanted cells in swine hearts with acute myocardial infarction (AMI) and reperfusion.</p><p><b>METHODS</b>Twenty-eight Chinese mini-pigs were divided into four groups including a control group (n = 7); group 2, administration of low-dose TXL alone from the 3rd day prior to AMI to the 4th day post transplantation (n = 7); group 3, MSCs alone (n = 7) and group 4, TXL + MSCs (n = 7). AMI models were made by occlusion of the left anterior descending coronary artery for 90 minutes. Autologous bone marrow-MSCs (3 x 10(7) cells/animal) were then injected into the post-infarct myocardium immediately after AMI and reperfusion. The survival and differentiation of implanted cells in vivo were detected by immunofluorescent analysis. The data of cardiac function were obtained at baseline (1 week after transplantation) and endpoint (6 weeks after transplantation) by single photon emission computed tomography (SPECT) and magnetic resonance imaging (MRI). Apoptosis was detected by TUNEL assay and the oxidative stress level was investigated in the post-infarct myocardium at endpoint.</p><p><b>RESULTS</b>At endpoint, there was less fibrosis and inflammatory cell infiltration with more surviving myocardium in group 4 than in the control group. In group 4 the survival and differentiation of implanted MSCs were significantly improved more than that seen in group 3 alone (P < 0.0001); the capillary density was also significantly greater than in the control group, group 2 or 3 both in the infarcted zone (P < 0.0001) and the peri-infarct zone (P < 0.0001). MRI showed that parameters at baseline were not significantly different between the 4 groups. At endpoint, regional wall thickening and the left ventricular ejection fraction were increased while the left ventricular mass index, dyskinetic segments and infarcted size were decreased only in group 4 compared with control group (P < 0.0001). SPECT showed that the area of perfusion defect was significantly decreased at endpoint only in group 4 compared with control group (P < 0.0001). TUNEL assay indicated that TXL administration significantly decreased cell apoptosis in peri-infarct myocardium in groups 2 and 4. Furthermore, superoxide dismutase (SOD) significantly increased and malondialdehyde (MDA) decreased in groups 2 and 4 by the administration of TXL.</p><p><b>CONCLUSIONS</b>Our study demonstrates the following: (1) immediate intramyocardial injection of MSCs after AMI and reperfusion resulted in limited survival and differentiation potential of implanted cells in vivo, thus being incapable of beneficially affecting post-hearts; (2) TXL-facilitation resulted in a significant survival and differentiation potential of implanted cells in vivo via inhibition of apoptosis and oxidative stress, accompanied by significant benefits in cardiac function.</p>

[Therapeutical effects of esculentoside A on rats with MsPGN induced by anti-Thy1.1 antibody].

OBJECTIVE: To observe the therapeutical effects of esculentoside A (EsA) on rats with mesangial proliferative glomerulonephritis (MsPGN) induced by anti-Thy1.1 antibody and make a comparison of the effects between EsA and dexamethasone (DXM). METHODS: Wistar rats with MsPGN induced by anti-Thy1.1 serum (ATS) were randomly divided into 3 groups: EsA group, DXM group, and model group. Moreover, a normal group was used for comparison. The BUN, SCr, urinary protein and renal pathological changes were examined after 7 d treatment with EsA and DXM. RESULTS: The urinary protein, cell count and mesangium area of glomerulus were significantly higher in all modeled groups than in normal group (P<0.001-0.05), and they were significantly lower in the treated groups than in untreated group (P<0.001-0.01). CONCLUSION: The results suggest that EsA is effective for reducing the urinary protein excretion and inhibiting the proliferation process of glomerular mesangium and matrix in rats with MsPGN.