TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium-induced inflammatory bowel disease through activation of the TLR4/NF-κBs pathway.

INTRODUCTION: Inflammatory bowel disease (IBD), which mainly leads to diarrhea, fatigue, stool blood, abdominal pain, and cramping, is threatening public health. Tripartite motif-containing 52 (TRIM52) has been reported to play an important role in inflammatory responses via activating the toll-like receptor 4 (TLR4)/nuclear factor-κB (NF-κB) pathway. However, the causes of IBD need to be elucidated, and the function of TRIM52 in IBD remains unclear. Here, we demonstrated that TRIM52 aggravated inflammation and pyroptosis in dextran sulfate sodium (DSS)-induced IBD by activating TLR4/NF-κBs pathway. METHODS: The colitis model was established on mice through DSS induction. For the TRIM52 knockdown, the mice were infected with a recombinant adenoviral vector expressing sgRNAs targeting TRIM52. RT-qPCR, western blot, and immunohistochemistry were performed to verify TRIM52 expression in DSS-induced IBD. The body weight, disease activity index, colon length, and H&E staining were used to assess the IBD symptoms in mice with TRIM52 knockdown. The inflammatory responses were examined by RT-qPCR and ELISA measuring tumor necrosis factor-α (TNF-α), inter-leukin 6 (IL-6), and interleukin 1ß (IL-1ß). Furthermore, the pyroptosis in colon tissue was detected by western blot. Finally, the TLR4/NF-κBs pathway activity was also examined by western blot. RESULTS: TRIM52 expression was up-regulated in DSS-induced IBD, and knockdown of TRIM52 could alleviate the symptoms of IBD. TRIM52 knockdown retarded DSS-induced inflammatory response and inhibited DSS-induced pyroptosis in colon tissue. In addition, TRIM52 played a role in activating TLR4/NF-κBs pathway. CONCLUSION: Knockdown of TRIM52 alleviated inflammation and pyroptosis in IBD by regulating TLR4/NF-κBs pathway. TRIM52 is expected to be a novel diagnostic indicator for IBD and a target of therapeutic treatment.

Outcomes of atrial fibrillation in patients with COVID-19 pneumonia: A systematic review and meta-analysis.

BACKGROUND: Recently, emerging evidence has suggested that atrial fibrillation (AF) has an epidemiological correlation with coronavirus disease 2019 (COVID-19). However, the clinical outcomes of AF in COVID-19 remain inconsistent and inconclusive. The aim of this study was to provide a comprehensive description of the impact of AF on the prognosis of patients with COVID-19 pneumonia. METHODS: Three electronic databases (PubMed, Embase, and Web of Science) were searched for eligible studies as of March 1, 2021. Pooled odds ratios (ORs) and 95% confidence intervals (CIs) were used to evaluate the associations between AF (preexisting and new-onset) and in-hospital mortality, post-discharge mortality, and ventilator use. RESULTS: A total of 36 individual studies were incorporated into our meta-analysis. The combined results revealed that preexisting AF was associated with increased in-hospital mortality (pooled OR: 2.07; 95% CI: 1.60-2.67; p < 0.001), post-discharge mortality (pooled OR: 2.69; 95% CI: 1.24-5.83; p < 0.05), and ventilator utilization (pooled OR: 4.53; 95% CI: 1.33-15.38; p < 0.05) in patients with COVID-19. In addition, our data demonstrated that new-onset AF during severe acute respiratory syndrome coronavirus 2 infection was significantly correlated with increased mortality (pooled OR: 2.38; 95% CI: 2.04-2.77; p < 0.001). CONCLUSIONS: The presence of AF is correlated with adverse outcomes in patients with COVID-19 pneumonia, which deserves increased attention and should be managed appropriately to prevent adverse outcomes.

Outcomes of new-onset atrial fibrillation in patients with sepsis: A systematic review and meta-analysis of 225,841 patients.

BACKGROUND: The outcomes of new-onset atrial fibrillation (AF) during sepsis are inconsistent and inconclusive. This meta-analysis aims to provide a comprehensive description of the impact of new-onset AF on the prognosis of sepsis. METHODS: Three electronic databases (PubMed, Embase, and the Cochrane Library) were searched for relevant studies. Meta-analysis was performed using odds ratios (OR) and 95% confidence intervals (CI) as effect measures. RESULTS: A total of 225,841 patients from 13 individual studies were incorporated to the meta-analysis. The summary results revealed that new-onset AF during sepsis was associated with increased odds of in-hospital mortality (pooled OR: 2.09; 95% CI: 1.53-2.86; p < 001), post-discharge mortality (pooled OR: 2.44; 95% CI: 1.81-3.29; p < .001), and stroke (pooled OR:1.88; 95% CI: 1.13-3.14; p < .05). Results also indicated that the incidence of new-onset AF varied from 1.9% for mild sepsis to 46.0% for septic shock. Furthermore, compared to those without AF, people with new-onset AF had longer ICU and hospital stays, as well as a higher recurrence of AF. CONCLUSIONS: New-onset AF is frequently associated with adverse outcomes in patients with sepsis. This is a clinical issue that warrants more attention and should be managed appropriately to prevent poor prognosis.

Transforaminal endoscopic decompression for thoracic spinal stenosis under local anesthesia.

BACKGROUND: Thoracic spinal stenosis is a common vertebral degenerative disease, and treatment remains challenging. In recent years, transforaminal endoscopic decompression has been widely used for treating lumbar degenerative diseases. However, the efficacy of this procedure for thoracic spinal stenosis has yet to be established. Herein, we report a case of thoracic spinal stenosis treated with transforaminal endoscopic decompression under local anesthesia. CASE REPORT: An 88-year-old man presented with a 1-month history of progressive paralysis and dysesthesia in the bilateral lower extremities. A diagnosis of thoracic spinal stenosis was made, based on physical examination. A two-step percutaneous transforaminal endoscopic thoracic decompression was performed for spinal canal decompression. Over a follow-up of 1 year, a favorable outcome was noted. CONCLUSION: Transforaminal endoscopic decompression is a safe and an effective surgical approach for the treatment of thoracic spinal stenosis. For patients with thoracic spinal stenosis, accurate diagnosis and elaborate surgical planning should be highlighted, and the surgical outcome can be favorable.

Use of deep sequencing to profile small RNAs derived from tomato spotted wilt orthotospovirus and hippeastrum chlorotic ringspot orthotospovirus in infected Capsicum annuum.

Virus-derived small RNAs are one of the key factors of RNA silencing in plant defence against viruses. We obtained virus-derived small interfering RNA profiles from Tomato spotted wilt orthotospovirus and Hippeastrum chlorotic ringspot orthotospovirus infected Capsicum annuum XX19 and XY11 by deep sequencing one day after inoculation. The vsiRNAs data were mapped to the TSWV and HCRV genomes, and the results showed that the vsiRNAs measured 19-24 nucleotides in length. Most of the vsiRNAs were mapped to the S segment of the viral genome. For XX19 and XY11 infected with HCRV, the distribution range of vsiRNAs in S RNA was 52.06-55.20%, while for XX19 and XY11 infected with TSWV, the distribution range of vsiRNAs in S RNA was 87.76-89.07%. The first base at the 5' end of the siRNA from TSWV and HCRV was primarily biased towards A, U, or C. Compared with mock-inoculated XX19 and XY11, the expression level of CaRDR1 was upregulated in TSWV- and HCRV-inoculated XX19 and XY11. CaAGO2 and CaAGO5 were upregulated in XY11 against HCRV infection, and CaRDR2 was downregulated in TSWV-infected XY11 and XX19. The profile of HCRV and TSWV vsiRNA verified in this study could be useful for selecting key vsiRNA such as those in disease-resistant varieties by artificially synthesizing amiRNA.

[PTEN: a new target in inhibiting of tumor invasion and metastasis].

Invasion and metastasis are both the main biological characteristics in malignant tumor which are influence tumor therapeutic effect and prognosis. The tumor cells interact with vascular endothelial cells and cell matrix, penetrate vascular endothelial and degrade the extracellular matrix, and metastasis to the local and distant by the interactions of a variety of signaling molecules. PTEN protein has protein phosphatase and lipid phosphatase dual activity which is produced by PTEN gene. As a tumor suppressor gene, regulates the cell signal pathways to sustain the normal physiological functions, negatively regulates of tumor cell growth and cell cycle, induces apoptosis, and inhibits invasion, infiltrating and metastasis of tumor cells. This article is reviewed about how PTEN participates in inhibiting tumor cell invasion and metastasis.

Diastereoselective [3 + 1] Cyclization Reaction of Oxindolyl Azaoxyallyl Cations with Sulfur Ylides: Assembly of 3,3'-Spiro[ß-lactam]-oxindoles.

Oxindoles and ß-lactams are attractive structural motifs because of their unique biological importance. However, the fusion of the two moieties featuring 3,3'-spirocyclic scaffolds is a challenging task in organic synthesis. Herein we designed a novel type of oxindole-based azaoxyallyl cation synthons, which could readily participate in the [3 + 1] cyclization with sulfur ylides. With this protocol, a collection of 3,3-spiro[ß-lactam]-oxindoles were facilely produced in up to 94% yield with perfect diastereoselectivity.

Construction of a Benzo[b]azepine Skeleton through Decarboxylative Ylide [6+1] Annulations with Modified Vinyl Benzoxazinanones.

A Lewis acid-promoted [6+1] annulation between sulfur ylides and modified vinyl benzoxazinanones was described. In this reaction, the newly designed vinyl benzoxazinanones could serve as a novel six-atom synthon, and the key to success is the installation of an electron-withdrawing group on the alkene moiety of the benzoxazinanones. A broad range of substrates are compatible with this mild reaction system, thereby providing a facile and practical approach for constructing a benzo[b]azepine skeleton.

Epidural Spinal Cord Stimulation Promotes Motor Functional Recovery by Enhancing Oligodendrocyte Survival and Differentiation and by Protecting Myelin after Spinal Cord Injury in Rats.

Epidural spinal cord stimulation (ESCS) markedly improves motor and sensory function after spinal cord injury (SCI), but the underlying mechanisms are unclear. Here, we investigated whether ESCS affects oligodendrocyte differentiation and its cellular and molecular mechanisms in rats with SCI. ESCS improved hindlimb motor function at 7 days, 14 days, 21 days, and 28 days after SCI. ESCS also significantly increased the myelinated area at 28 days, and reduced the number of apoptotic cells in the spinal white matter at 7 days. SCI decreased the expression of 2',3'-cyclic-nucleotide 3'-phosphodiesterase (CNPase, an oligodendrocyte marker) at 7 days and that of myelin basic protein at 28 days. ESCS significantly upregulated these markers and increased the percentage of Sox2/CNPase/DAPI-positive cells (newly differentiated oligodendrocytes) at 7 days. Recombinant human bone morphogenetic protein 4 (rhBMP4) markedly downregulated these factors after ESCS. Furthermore, ESCS significantly decreased BMP4 and p-Smad1/5/9 expression after SCI, and rhBMP4 reduced this effect of ESCS. These findings indicate that ESCS enhances the survival and differentiation of oligodendrocytes, protects myelin, and promotes motor functional recovery by inhibiting the BMP4-Smad1/5/9 signaling pathway after SCI.

Regiodivergent construction of medium-sized heterocycles from vinylethylene carbonates and allylidenemalononitriles.

Medium-sized heterocycles exist in a broad spectrum of biologically active natural products and medicinally important synthetic compounds. The construction of medium-sized rings remains challenging, particularly the assembly of different ring sizes from the same type of substrate. Here we report palladium-catalyzed, regiodivergent [5 + 4] and [5 + 2] annulations of vinylethylene carbonates and allylidenemalononitriles. We describe the production of over 50 examples of nine- and seven-membered heterocycles in high isolated yields and excellent regioselectivities. We demonstrate the synthetic utility of this approach by converting a nine-membered ring product to an interesting polycyclic caged molecule via a [2 + 2] transannulation. Mechanistic studies suggest that the [5 + 2] annulation proceeds through palladium-catalyzed ring-opening/re-cyclization from the [5 + 4] adducts.

Preservation of heart function in diabetic rats by the combined effects of muscle cell implantation and insulin therapy.

BACKGROUND: Diabetic cardiomyopathy is a common cause of heart failure in diabetic patients, but current treatments do not directly improve ventricular function. Cell transplantation can prevent cardiac dilatation after injury, and may also prevent congestive heart failure in diabetic cardiomyopathy. AIM: This study evaluated the functional effects of smooth muscle cells (SMCs) implanted into the myocardium of insulin- and non insulin-treated diabetic rats. METHODS: Four weeks after streptozotocin infusion, adult Wistar rats were implanted with BrdU-labelled SMCs or culture media (N=12/group). Six rats in each group were also treated with insulin. Echocardiograms were performed at 0, 4 and 8 weeks after streptozotocin injection, and histology and heart function were evaluated at 4 weeks after implantation. RESULTS: Blood glucose levels decreased after insulin treatment. Among cell-injected rats, histology indicated that those that did not receive insulin retained fewer surviving BrdU+ SMCs, and a smaller volume of myocardial tissue positive for alpha-smooth muscle actin. Cardiac function was preserved in the insulin-treated groups relative to those that did not receive insulin. Among insulin-treated rats, the cell-injected group functioned better than the media-injected group. CONCLUSIONS: Diabetic cardiomyopathy is partially treatable with insulin; however, a combination of SMC transplantation and insulin treatment produced the best functional result. Cell transplantation may prevent the progression of diabetic cardiomyopathy in patients whose glucose levels are controlled with insulin.

Ebselen protects mitochondrial function and oxidative stress while inhibiting the mitochondrial apoptosis pathway after acute spinal cord injury.

Ebselen is a fat-soluble small molecule and organic selenium compound that regulates the activity of glutathione peroxidase to alleviate mitochondrial oxidative stress and improve mitochondrial function. In the present study, we aimed to investigate the effects of ebselen on mitochondrial oxidative stress response, mitochondrial apotosis, and motor behaviors after spinal cord injury (SCI). We found that ebselen significantly increased the BBB score in motor behavior, thus suggesting a rescue effect of ebselen on motor function after SCI in rats. Meanwhile, we revealed that ebselen can increase glutathione (GSH) content as well as superoxide dismutase (SOD) and catalase (CAT) activities after SCI-this suggests ebselen has an antioxidant effect. Furthermore, the ATP content and Na+-K+-ATPase activity in mitochondria were increased by ebselen after SCI, while the mitochondrial membrane potential (MMP) was decreased by ebselen. The Cytochrome C and Smac release from mitochondria were reduced by ebselen after SCI, thus indicating improved membrane permeability by ebselen. Moreover, the alterations in caspase-3, Bax and Bcl-2 protein expression, as well as the proportion of cell apoptosis were improved by ebselen treatment, which together suggested that ebselen has an inhibitory effect on mitochondrial apotosis pathways after SCI. Taken together, our results suggest that ebselen can inhibit secondary damage caused by spinal cord injury. Indeed it plays a neuroprotective role in spinal cord injury perhaps by improving mitochondrial function and inhibiting the mitochondrial apoptosis pathway.

Exendin-4 Enhances Motor Function Recovery via Promotion of Autophagy and Inhibition of Neuronal Apoptosis After Spinal Cord Injury in Rats.

Autophagy occurs prior to apoptosis and plays an important role in cell death regulation during spinal cord injury (SCI). This study aimed to determine the effects and potential mechanism of the glucagon-like peptide-1 (GLP-1) agonist extendin-4 (Ex-4) in SCI. Seventy-two male Sprague Dawley rats were randomly assigned to sham, SCI, 2.5 µg Ex-4, and 10 µg Ex-4 groups. To induce SCI, a 10-g iron rod was dropped from a 20-mm height to the spinal cord surface. Ex-4 was administered via intraperitoneal injection immediately after surgery. Motor function evaluation with the Basso Beattie Bresnahan (BBB) locomotor rating scale indicated significantly increased scores (p < 0.01) in the Ex-4-treated groups, especially 10 µg, which demonstrated the neuroprotective effect of Ex-4 after SCI. The light chain 3-II (LC3-II) and Beclin 1 protein expression determined via western blot and the number of autophagy-positive neurons via immunofluorescence double labeling were increased by Ex-4, which supports promotion of autophagy (p < 0.01). The caspase-3 protein level and neuronal apoptosis via transferase UTP nick end labeling (TUNEL)/NeuN/DAPI double labeling were significantly reduced in the Ex-4-treated groups, which indicates anti-apoptotic effects (p < 0.01). Finally, histological assessment via Nissl staining demonstrated the Ex-4 groups exhibited a significantly greater number of surviving neurons and less cavity (p < 0.01). To our knowledge, this is the first study to indicate that Ex-4 significantly enhances motor function in rats after SCI, and these effects are associated with the promotion of autophagy and inhibition of apoptosis.

Time representation of mitochondrial morphology and function after acute spinal cord injury.

Changes in mitochondrial morphology and function play an important role in secondary damage after acute spinal cord injury. We recorded the time representation of mitochondrial morphology and function in rats with acute spinal cord injury. Results showed that mitochondria had an irregular shape, and increased in size. Mitochondrial cristae were disordered and mitochondrial membrane rupture was visible at 2-24 hours after injury. Fusion protein mitofusin 1 expression gradually increased, peaked at 8 hours after injury, and then decreased to its lowest level at 24 hours. Expression of dynamin-related protein 1, amitochondrial fission protein, showed the opposite kinetics. At 2-24 hours after acute spinal cord injury, malondialdehyde content, cytochrome c levels and caspase-3 expression were increased, but glutathione content, adenosine triphosphate content, Na(+)-K(+)-ATPase activity and mitochondrial membrane potential were gradually reduced. Furthermore, mitochondrial morphology altered during the acute stage of spinal cord injury. Fusion was important within the first 8 hours, but fission played a key role at 24 hours. Oxidative stress was inhibited, biological productivity was diminished, and mitochondrial membrane potential and permeability were reduced in the acute stage of injury. In summary, mitochondrial apoptosis is activated when the time of spinal cord injury is prolonged.

Acetyl-L-carnitineameliorates mitochondrial damage and apoptosis following spinal cord injury in rats.

Acetyl-l-carnitine (ALC) facilitates the entry and exit of fatty acids from mitochondria and plays an essential role in energy metabolism. Although ALC is known to exert neuroprotective effects in multiple neurological diseases, its effects on spinal cord injury (SCI)-induced mitochondrial impairments and apoptosis remain unclear. In this study, we aimed to evaluate the putative effects of ALC on mitochondrial dysfunction and apoptosis induced by SCI in a rodent model. Our results indicate that SCI elicits dynamic alternations in the expression of mitochondria-related proteins. Transmission electron microscopy analysis showed that ALC administration abrogated key ultrastructural abnormalities in mitochondria at 24h after SCI by maintaining mitochondrial length, reducing the number of damaged mitochondria, and reversing mitochondrial score (P<0.05 compared with SCI group). In addition, ALC administration maintained the mitochondrial membrane potential and mitochondrial Na(+)-K(+)-ATPase activity following SCI (P<0.05 compared with SCI group). ALC administration reversed the downregulation of mitofusin 1 (Mfn1), Mfn2, Bcl-2, and the upregulation of dynamin-related protein 1 (Drp1), mitochondrial fission 1 (Fis1), Bcl-2-associated X protein (Bax) and cytosol cytochrome c (cyto-CytC) induced by SCI (P<0.05 compared with SCI group). Finally ALC administration greatly reduced the percentage of apoptotic cells compared with the SCI group (P<0.01). In conclusion, our findings demonstrated that ALC ameliorated SCI-induced mitochondrial structural alternations, mitochondrial dysfunction, and apoptosis.

Tetramethylpyrazine induces SH-SY5Y cell differentiation toward the neuronal phenotype through activation of the PI3K/Akt/Sp1/TopoIIß pathway.

Tetramethylpyrazine (TMP) is an active compound extracted from the traditional Chinese medicinal herb Chuanxiong. Previously, we have shown that TMP induces human SH-SY5Y neuroblastoma cell differentiation toward the neuronal phenotype by targeting topoisomeraseIIß (TopoIIß), a protein implicated in neural development. In the present study, we aimed to elucidate whether the transcriptional factors specificity protein 1 (Sp1) and nuclear factor Y (NF-Y), in addition to the upstream signaling pathways ERK1/2 and PI3K/Akt, are involved in modulating TopoIIß expression in the neuronal differentiation process. We demonstrated that SH-SY5Y cells treated with TMP (80µM) terminally differentiated into neurons, characterized by increased neuronal markers, tubulin ßIII and microtubule associated protein 2 (MAP2), and increased neurite outgrowth, with no negative effect on cell survival. TMP also increased the expression of TopoIIß, which was accompanied by increased expression of Sp1 in the differentiated neuron-like cells, whereas NF-Y protein levels remained unchanged following the differentiation progression. We also found that the phosphorylation level of Akt, but not ERK1/2, was significantly increased as a result of TMP stimulation. Furthermore, as established by chromatin immunoprecipitation (ChIP) assay, activation of the PI3K/Akt pathway increased Sp1 binding to the promoter of the TopoIIß gene. Blockage of PI3K/Akt was shown to lead to subsequent inhibition of TopoIIß expression and neuronal differentiation. Collectively, the results indicate that the PI3K/Akt/Sp1/TopoIIß signaling pathway is necessary for TMP-induced neuronal differentiation. Our findings offer mechanistic insights into understanding the upstream regulation of TopoIIß in neuronal differentiation, and suggest potential applications of TMP both in neuroscience research and clinical practice to treat relevant diseases of the nervous system.

Vascular endothelial growth factor transgene expression in cell-transplanted hearts.

OBJECTIVE: We evaluated the effect of transplanted cell type, time, and region of the heart on transgene expression to determine the potential of combined gene and cell delivery for myocardial repair. METHODS: Lewis rats underwent myocardial cryoinjury 3 weeks before transplantation with heart cells (a mixed culture of cardiomyocytes, smooth muscle cells, endothelial cells and fibroblasts, n = 13), vascular endothelial growth factor-transfected heart cells (n = 13), skeletal myoblasts (n = 13), vascular endothelial growth factor-transfected skeletal myoblasts (n = 13), or medium (control, n = 12). Vascular endothelial growth factor expression in the scar, border zone, and normal myocardium was evaluated at 3 days and at 1, 2, and 4 weeks by means of quantitative polymerase chain reaction. Transplanted cells and vascular endothelial growth factor protein were identified immunohistologically on myocardial sections. RESULTS: Vascular endothelial growth factor levels were very low in control scars but increased transiently after medium injection. Transplantation with heart cells and skeletal myoblasts significantly increased vascular endothelial growth factor expression in the scar and border zone. Transplantation of vascular endothelial growth factor-transfected heart cells and vascular endothelial growth factor-transfected skeletal myoblasts further augmented vascular endothelial growth factor expression, resulting in 4- to 5-fold greater expression of vascular endothelial growth factor in the scar at 1 week. Peak vascular endothelial growth factor expression was greater and earlier in vascular endothelial growth factor-transfected heart cells than in vascular endothelial growth factor-transfected skeletal myoblasts. Vascular endothelial growth factor was primarily expressed by the transplanted cells. Some of the transplanted heart cells and vascular endothelial growth factor-transfected heart cells were identified in the endothelial layer of blood vessels in the scar. CONCLUSIONS: Transplantation of heart cells and skeletal myoblasts induces vascular endothelial growth factor expression in myocardial scars and is greatly augmented by prior transfection with a vascular endothelial growth factor transgene. Vascular endothelial growth factor expression is limited to the scar and border zone for 4 weeks. Both heart cells and skeletal myoblasts may be excellent delivery vehicles for cell-based myocardial gene therapy.

Improved heart function with myogenesis and angiogenesis after autologous porcine bone marrow stromal cell transplantation.

OBJECTIVE: The study evaluated the utility of transplanting bone marrow stromal cells in a porcine myocardial infarction model. METHODS: A myocardial infarction was created by occluding the distal left anterior descending artery in pigs with coils and Gelfoam sponge. Sternal bone marrow was aspirated, and stromal cells were cultured and induced to differentiate to a myogenic phenotype with 5-azacytidine. Four weeks after coronary artery occlusion, sestamibi technetium single-photon emission computed tomographic scans were performed, and then either a graft of 100 x 10(6) bone marrow stromal cells (n = 5, 30% labeled with bromodeoxyuridine) or culture medium (n = 6) was injected into the infarct region. Four weeks later the tomographic scans were repeated and cardiac function was assessed with pressure and volume measurements. Morphologic and histologic characteristics of the heart were also studied. RESULTS: Histologic examination found bromodeoxyuridine-labeled cells within the infarct region in islands that had sarcomeres and Z-bands and stained positively for cardiac specific troponin I. The bone marrow stromal cell transplant sites had a greater (P <.05) capillary density than did the control sites. The tomographic scans showed that the hearts with the cell transplants had increases in stroke volume, regional perfusion, and wall motion (P <.05 for all groups) relative to the control hearts. The pressure-volume analysis showed improvement (P <.05) in end-systolic elastance and preload recruitable stroke work in the transplantation group relative to the control group. The left ventricular chamber size was smaller (P <.05) and the scar thickness was greater (P <.05) in the hearts with transplanted cells than in the control hearts (P =.06). CONCLUSION: 5-Azacytidine-treated bone marrow stromal cells transplanted into the myocardial infarct region formed islands of cardiac-like tissue, induced angiogenesis, prevented thinning and dilatation of the infarct region, and improved regional and global contractile function.

Beneficial effect of autologous cell transplantation on infarcted heart function: comparison between bone marrow stromal cells and heart cells.

BACKGROUND: Cell transplantation may restore function after myocardial infarction, but the optimal cell type remains controversial. We compared autologous bone marrow stromal cells (BMCs) with autologous heart cells (HCs) in a porcine myocardial infarction model. METHODS: Yorkshire pigs underwent coil occlusion of the left anterior descending artery. Bone marrow stromal cells were obtained from sternal marrow and HCs were obtained by left ventricular biopsy, then cultured for 4 weeks. Four weeks after infarction, a 99mTc-sestamibi single-photon emission tomography (99mTc-MIBI SPECT) scan was performed and the pigs were then transplanted with BMCs (n = 7), HCs (n = 7), or culture medium (n = 14). Four weeks after transplantation, 99mTc-MIBI SPECT scanning was repeated to evaluate regional perfusion. Pressure-volume loops were constructed from micromanometer and conductance catheter data to evaluate left ventricular function. Hearts were evaluated histologically. RESULTS: Bone marrow stromal cells and HCs engrafted within the infarct and assumed a myocyte morphology. SPECT MIBI scans showed increased perfusion in the infarct in cell-transplanted pigs, while perfusion decreased in the control pigs. Heart cell transplantation improved preload-recruitable stroke work and HC and BMC transplantation both shifted the end-systolic pressure-volume relation to the left. Both BMCs and HCs prevented thinning and expansion of the infarct region, and some BMCs differentiated into endothelial cells in newly formed blood vessels perfusing the infarct. CONCLUSIONS: Both BMCs and HCs engrafted in the infarct region and improved let ventricular function by preventing infarct thinning. Bone marrow stromal cells demonstrated greater plasticity in vivo, and may offer a practical alternative to HC transplantation to restore function and perfusion after a myocardial infarction.

Iso-suillin isolated from Suillus luteus, induces G1 phase arrest and apoptosis in human hepatoma SMMC-7721 cells.

Iso-suillin, a natural product isolated from Suillus luteus, has been shown to inhibit the growth of some cancer cell lines. However, the molecular mechanisms of action of this compound are poorly understood. The purpose of this study was to investigate how iso-suillin inhibits proliferation and induces apoptosis in a human hepatoma cell line (SMMC-7721). We demonstrated the effects of iso-suillin on cell proliferation and apoptosis in SMMC-7721 cells, with no apparent toxicity in normal human lymphocytes, using colony formation assays and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) analysis. Western blotting was used to examine the expression of G1 phase-regulated and apoptosis-associated protein levels in iso-suillin treated SMMC-7721 cells. The results indicated that iso-suillin significantly decreased viability, induced G1 phase arrest and triggered apoptosis in SMMC-7721cells. Taken together, these results suggest the potential of iso-suillin as a candidate for liver cancer treatment.