The implications and prospect of cuproptosis-related genes and copper transporters in cancer progression.

Currently, cancer has become one of the major public health problems worldwide. Apoptosis is an important anti-cancer defense mechanism, which is used in the development of targeted drugs. Because cancer cells have endogenous resistance to apoptosis,the clinical efficacy of related drugs is not ideal. Therefore, non-apoptotic regulatory cell death may bring new therapeutic strategies for cancer treatment. Cuproptosis is a novel form of regulatory cell death which is copper-dependent, regulated and distinct from other known cell death regulatory mechanisms. FDX1,LIAS,and DLAT named cuproptosis-related genes play an essential role in regulating cuproptosis. Meanwhile, abnormal accumulation of copper can be observed in various malignant tumors. The correlation has been established between elevated copper levels in serum and tissues and the progression of several cancers. Copper transporters, CTR1 and Copper-transporting ATPases(ATP7A and ATP7B), are mainly involved in regulating the dynamic balance of copper concentration to maintain copper homeostasis. Thus,cuproptosis-related genes and copper transporters will be the focus of cancer research in future. This review elaborated the basic functions of cuproptosis-related genes and copper transporters by retrievalling PubMed. And then we analyzed their potential relationship with cancer aiming to provide theoretical support and reference in cancer progression, diagnosis and treatment for future study.

Ligustrazine Inhibits the Migration and Invasion of Renal Cell Carcinoma.

Ligustrazine is a Chinese herb (Chuanxiong) approved for use as a medical drug in China. Recent evidence suggests that ligustrazine has promising antitumor properties. Our preliminary results showed that ligustrazine could inhibit the growth of human renal cell carcinoma (RCC) cell lines. However, the complicated molecular mechanism has not been fully revealed. Therefore, the purpose of this study to investigate the mechanism of ligustrazine resistance in human RCC cells. Cell proliferation, migration, invasion, and colony-formation ability of RCC cells A498 were detected by MTT assay, clonal formation rates, and transwell chamber assay in vitro. The expression of epithelial-mesenchymal transition (EMT)-related proteins were analyzed using western blot test. The effect of ligustrazine on the growth of A498 cells in nude mice was investigated in vivo. Our results showed that ligustrazine could significantly inhibit the proliferation, migration, and invasion of A498 both in vivo and vitro. Western blot analysis showed that the expressions of EMT-related, N-cadherin, snail, and slug proteins were significantly decreased in A498 in the ligustrazine treatment group. This study indicated that ligustrazine could significantly inhibit the malignant biological behaviors of RCC cell lines, possibly by inhibiting the EMT process.

Diagnostic significance of serum type IV collagen (IVC) combined with aspartate aminotransferase (AST)/alanine aminotransferase (ALT) ratio in liver fibrosis.

Background: Liver fibrosis is a necessary stage for various chronic liver diseases to develop into cirrhosis. The detection of serum markers of liver fibrosis is a commonly used method for early screening of liver fibrosis, mainly including type IV collagen (IVC), hyaluronic acid (HA), laminin (LN), and type III procollagen (PCIII). However, the high cost of the instrument and the slow detection speed are not conducive to mass screening and detection of the population. In this study, the widely used biochemical platform was used to jointly detect the liver fibrosis marker IVC and aspartate aminotransferase (AST) and alanine aminotransferase (ALT), We investigated the feasibility of serum IVC combined with the AST and ALT ratio (AST/ALT ratio) as a marker for liver fibrosis. Methods: A total of 81 patients with liver disease by clinical liver biopsy comprised the study group, and 50 healthy people who underwent physical examination in the study period were selected as the control group. Serum IVC, AST and ALT levels were detected by biochemical testing, AST/ALT ratio was calculated, and four serum markers of liver fibrosis (IVC, HA, LN, and PCIII) were measured by chemiluminescence. Moreover, imaging by color Doppler ultrasound (B-ultrasound) was performed for statistical analysis. Results: (I) Serum IVC and the AST/ALT ratio were significantly higher in the study group than in the control group (P<0.05). (II) The sensitivity of serum IVC combined with AST/ALT ratio detected biochemically and the four markers of liver fibrosis detected by chemiluminescence in the diagnosis of liver cirrhosis was 95.83%, 97.92%, without significant difference, but the specificity and accuracy of IVC + AST/ALT ratio in the diagnosis of liver cirrhosis were significantly higher (94.00%, 94.90%). (III) The detection rate of serum IVC + AST/ALT ratio for the diagnosis of early liver fibrosis was significantly higher than with imaging examination (45.45% vs. 21.21%). Conclusions: Serum IVC + AST/ALT ratio determined by biochemical analysis has high diagnostic accuracy in the diagnosis of liver fibrosis and liver cirrhosis, and is worthy of clinical application and promotion.

The role of TXNL1 in disease: treatment strategies for cancer and diseases with oxidative stress.

Thioredoxin-like protein-1 (TXNL1; also known as thioredoxin-related 32 kDa protein, TRP32) is a thioredoxin involved in the regulation of oxidative stress, which protects cells from damage through redox balance. Studies have shown that TXNL1 has a variety of functions, including cell signal transduction, cell cycle regulation, protein synthesis, modification and degradation, vesicle transport, transcriptional regulation, cell apoptosis, virus replication and oxidative stress regulation, etc., and plays an important role in the occurrence and development of human diseases. Therefore, TXNL1 has a strong correlation with the treatment of cancer and oxidative stress diseases. In this paper, the basic structure, function and potential application value of TXNL1 in diseases are reviewed, so as to open up new targets for the treatment of cancer and oxidative stress-related diseases.

Generation and identification of a conditional knockout allele for the PSMD11 gene in mice.

BACKGROUND: Our previous study have shown that the PSMD11 protein was an important survival factor for cancer cells except for its key role in regulation of assembly and activity of the 26S proteasome. To further investigate the role of PSMD11 in carcinogenesis, we constructed a conditional exon 5 floxed allele of PSMD11 (PSMD11flx) in mice. RESULTS: It was found that homozygous PSMD11 flx/flx mice showed normal and exhibited a normal life span and fertility, and showed roughly equivalent expression of PSMD11 in various tissues, suggesting that the floxed allele maintained the wild-type function. Cre recombinase could induce efficient knockout of the floxed PSMD11 allele both in vitro and in vivo. Mice with constitutive single allele deletion of PSMD11 derived from intercrossing between PSMD11flx/flx and CMV-Cre mice were all viable and fertile, and showed apparent growth retardation, suggesting that PSMD11 played a significant role in the development of mice pre- or postnatally. No whole-body PSMD11 deficient embryos (PSMD11-/-) were identified in E7.5-8.5 embryos in uteros, indicating that double allele knockout of PSMD11 leads to early embryonic lethality. To avoid embryonic lethality produced by whole-body PSMD11 deletion, we further developed conditional PSMD11 global knockout mice with genotype Flp;FSF-R26CAG - CreERT2/+; PSMD11 flx/flx, and demonstrated that PSMD11 could be depleted in a temporal and tissue-specific manner. Meanwhile, it was found that depletion of PSMD11 could induce massive apoptosis in MEFs. CONCLUSIONS: In summary, our data demonstrated that we have successfully generated a conditional knockout allele of PSMD11 in mice, and found that PSMD11 played a key role in early and postnatal development in mice, the PSMD11 flx/flx mice will be an invaluable tool to explore the functions of PSMD11 in development and diseases.

Protective effect of baicalin against pulmonary arterial hypertension vascular remodeling through regulation of TNF-α signaling pathway.

Pulmonary arterial hypertension (PAH) is a progressive cardiovascular disease with high mortality. However, there were no efficient medical drugs for PAH to enormously improve the survival and quality of life measures. The present study aimed to explore the protective effect of baicalin against experimental PAH in vivo and vitro. All the experimental rats received intraperitoneal injection of monocrotaline (MCT) to induce PAH model. Baicalin was given by intragastric administration from 2 days after MCT injection. Forty animals were randomly divided into four groups: Control, MCT, saline-, and baicalin-treated groups (n = 10 in each). Post-operation, hemodynamic data, and index of right ventricular hypertrophy (RVHI) were recorded to evaluate the inhibition of baicalin on MCT-induced PAH. Furthermore, pulmonary artery smooth muscle cells (PASMCs) model induced by tumor necrosis factor-α (TNF-α) was used to observe the inhibition of vascular cells proliferation in vitro. The results demonstrated that baicalin significantly attenuated MCT-induced right ventricular systolic pressure (RVSP), the index of right ventricular hypertrophy, and vessel wall thickness; inhibit inflammatory and cell proliferation induced by MCT or TNF-α, respectively. In addition, we found that baicalin might protect against experimental PAH via regulating the TNF-α/BMPR2 signaling pathway.

Mesenchymal Stromal Cell-derived Exosomes Attenuate Experimental Pulmonary Arterial Hypertension.

BACKGROUND: Pulmonary arterial Hypertension (PH) is a chronic disease that ultimately progresses to right ventricular failure and death. Until now, there is still a lack of effective treatment applied. The purpose of the present study was to observe the protective effect of Mesenchymal Stromal Cell-Derived Exosomes (MSC-EXO) against experimental Pulmonary arterial Hypertension (PH) and right ventricular failure. METHODS: All the experimental rats received an intraperitoneal injection of 50 mg/kg monocrotaline to induce PH model. Three weeks after the model was successfully established, the cell Culture Media (CM) or MSC-EXO derived from human umbilical cord was administered daily via the tail vein. All animals were randomly divided into 4 groups: Control (saline-treated), MCT-PH, MCT-CM and MCT-EXO groups. Post-operation, hemodynamic data and index of right ventricular hypertrophy (RVHI) were recorded to evaluate the inhibition of MSC-EXO on MCT-induced PH. Histology, immunohistochemistry and western blot were used to analyze the effect of MSC-EXO against vascular remodeling and further reveal the mechanism. RESULTS: In the present study, our results showed that MSC-EXO administration could significantly reduce the Right Ventricular Systolic Pressure (RVSP) and RVHI, suppress the pulmonary vascular remodeling and The Endothelial-Mesenchymal Transition (EndMT) process. CONCLUSION: Our results provided the firm information for a new method in the treatment of PH; the mechanism may be related to the inhibition of vascular remodeling and EndMT.

STAT1 transcriptionally regulates the expression of S1PR1 by binding its promoter region.

Sphingosine 1-phosphate receptor 1 (S1PR1) plays a pivotal role in mediating trafficking and migration of immune cells. Previous reports also identify S1PR1 as an important susceptibility gene of asthma and other autoimmune disorders. However, little has been known about the regulatory mechanism of S1PR1 expression. Thus we systematically investigated the transcriptional regulation of S1PR1 in this study. Promoter activity of S1PR1 gene was carefully screened using series of pGL3-Basic reporter vectors, containing full length (range from transcription start site to upstream -1 kb region) or several truncated fragments of S1PR1 promoter. We identified an area (from -29 to -12 bp) of the S1PR1 promoter as the minimal promoter region. Bioinformatics prediction results showed that several transcription factors were recruited to these sites. EMSA and ChIP assays demonstrated the transcriptional factor STAT1 could bind to the region. We also found that the level of S1PR1 level was significantly reduced when STAT1 was knocked-down. Consistent with the reduction of S1PR1 caused by depletion of STAT1, overexpression of STAT1 resulted in up-regulation of S1PR1. In addition, both mRNA and protein levels of S1PR1 were increased when STAT1 was activated by IFN-γ, and decreased when STAT1 was inhibited by fludarabine. Besides, the levels of STAT1 and S1PR1 expression were positively correlated in peripheral blood leukocytes derived from 41 healthy individuals. Our study showed that transcription factor STAT1 could bind to upstream region of -29 bp to -12 bp of the S1PR1 promoter and stimulate the expression of S1PR1.

Homoharringtonine could induce quick protein synthesis of PSMD11 through activating MEK1/ERK1/2 signaling pathway in pancreatic cancer cells.

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most devastating disease with the 5-year survival rate less than 6%. In this study, we investigated if inhibiting protein synthesis directly with homoharringtonine (HHT) could induce acute apoptosis in pancreatic cancer cells through quick depletion of multiple short-lived critical members of the central proteome, example, PSMD11(26S proteasome non-ATPase regulatory subunit 11). It was shown that although HHT could inhibit proliferation and growth of MiaPaCa-2 and PANC-1 cells in a time- and dose-dependent manner, only part of pancreatic cancer cells could be induced to die through acute apoptosis. Mechanistic studies showed that HHT could induce quick protein synthesis of PSMD11 through activating MEK1/ERK1/2 signaling pathway in pancreatic cancer cells. Inhibiting MEK1/ERK1/2 pathway with sorafenib could improve the cytotoxity of HHT in vitro and in a genetically engineered mouse model of pancreatic cancer. These results suggest that quick induction of PSMD11 or other acute apoptosis inhibitors through activation of the MEK1/ERK1/2 signaling pathway may be one of the important surviving mechanism which can help pancreatic cancer cells avoid acute apoptosis, it may have significant implications for the targeted therapy of pancreatic ductal adenocarcinoma.

Effects of Photodynamic Therapy Using Yellow LED-light with Concomitant Hypocrellin B on Apoptotic Signaling in Keloid Fibroblasts.

Keloid is a common and refractory disease characterized by abnormal fibroblast proliferation and excessive deposition of extracellular matrix components. Hypocrellin B (HB) is a natural perylene quinone photosensitizer. In this experiment, we studied the effects of photodynamic therapy (PDT) using yellow light from light-emitting diode (LED) combined with HB on keloid fibroblasts (KFB) in vitro. Our results showed that HB-LED PDT treatment induced significant KFB apoptosis and decreased KFB cell viability. HB-LED PDT treatment lead to significant BAX upregulation and BCL-2 downregulation in KFB cells, which led to elevation of intracellular free Ca2+ and activation of caspase-3. Our data provides preliminary evidence for the potential of HB-LED PDT as a therapeutic strategy for keloid.

Overexpression of NEDD9 in renal cell carcinoma is associated with tumor migration and invasion.

Scaffold protein neural precursor cell expressed, developmentally downregulated 9 (NEDD9) is a member of the Crk-associated substrate protein family and is known to be a biomarker in multiple cancer types. It serves a critical function in regulating cell proliferation, migration, invasion and survival. The objective of this study was to evaluate the potential effects of NEDD9 in renal cell carcinoma (RCC). The expression of NEDD9 was analyzed by immunohistochemistry, western blotting and reverse transcription-quantitative polymerase chain reaction. NEDD9 protein and mRNA levels were significantly upregulated in RCC tissues compared with normal tissues (P<0.001). Furthermore, the NEDD9 immunostaining level was significantly associated with primary tumor stage and tumor, node, metastasis stage (P<0.05). High NEDD9 expression resulted in significantly lower survival rates for patients compared with normal NEDD9 expression (P<0.01). In addition, wound healing and transwell assays indicated that NEDD9 depletion by small interfering RNA significantly attenuated the migration and invasion of RCC cells (P<0.001). The present data suggested that NEDD9 may be a novel target for prevention and treatment of RCC metastasis and recurrence.

MicroRNA­128a, BMI1 polycomb ring finger oncogene, and reactive oxygen species inhibit the growth of U­87 MG glioblastoma cells following exposure to X­ray radiation.

Radiotherapy is an important therapeutic strategy for the treatment of numerous types of malignant tumors, including glioma. However, radioresistance and anti­apoptotic mechanisms decrease the efficacy of radiotherapy in many patients with glioma. BMI1 polycomb ring finger oncogene (Bmi­1) is an oncogene associated with radioresistance in tumor cells. MicroRNA (miRNA)­128a is a brain-specific miRNA, which suppresses Bmi­1 expression. The present study investigated the effects of various radiation intensities on U­87 MG glioma cells, as well as the role of reactive oxygen species (ROS), Bmi­1, and miRNA­128a in the cellular response to radiotherapy. The response of U­87 MG cells following exposure to X­ray radiation was assessed using a cell growth curve and inhibition ratio. Cell cycle distribution and the levels of intracellular ROS were evaluated by flow cytometry. The mRNA expression levels of Bmi­1 and those of miRNA­128a in U­87 MG cells exposed to X­ray radiation were evaluated by reverse transcription­quantitative polymerase chain reaction. X­ray radiation did not decrease the number of U­87 MG cells; however, it did inhibit cellular growth in a dose­dependent manner. Following exposure to X­ray radiation for 24 h, cell cycle distribution was altered, with an increase in the number of cells in G0/G1 phase. The mRNA expression levels of Bmi­1 were downregulated in the 1 and 2 Gy groups, and upregulated in the 6 and 8 Gy groups. The expression levels of miRNA­128a were upregulated in the 1 and 2 Gy groups, and downregulated in the 8 Gy group. The levels of ROS were increased following exposure to ≥2 Gy, and treatment with N-acetyl cysteine was able to induce radioresistance. These results suggested that U­87 MG cells exhibited radioresistance. High doses of X­ray radiation increased the expression levels of Bmi­1, which may be associated with the evasion of cellular senescence. miRNA­128a and its downstream target gene Bmi­1 may have an important role in the radioresistance of U­87 MG glioma cells. In addition, ROS may be involved in the mechanisms underlying the inhibitory effects of X­ray radiation in U­87 MG cells, and the downregulation of ROS may induce radioresistance.

Therapeutic effects of baicalin on monocrotaline-induced pulmonary arterial hypertension by inhibiting inflammatory response.

BACKGROUND: Baicalin has been shown to possess various pharmacological actions, a recent study revealed that baicalin can attenuate pulmonary hypertension and pulmonary vascular remodeling through the inhibition of pulmonary artery smooth muscle cell proliferation, however, the potential mechanism remains unexplored. In this study, we investigated the therapeutic effect of baicalin on a rat model of monocrotaline (MCT)-induced pulmonary arterial hypertension (PAH) and attempted to further clarify the possible mechanisms underlying the anti-inflammatory. METHODS AND RESULTS: Our research showed that compared with MCT-induced PAH model rats, rats administered intragrastically with 100mg/kg baicalin showed the following after two weeks: the right ventricular systolic pressure (RVSP) and the right ventricle/left ventricle plus septum (RV/LV+S) ratio were lower (P<0.05); the intima thickening and luminal stenosis were improved (P<0.05); the mRNA levels of tumor necrosis factor alpha (TNF-α), interleukin-11ß (IL-1ß), IL-6, and endothelin-1 (ET-1) were obviously reduced by quantitative reverse transcription-polymerase chain reaction (qRT-PCR); the protein expression of transforming growth factor-ß1 (TGF-ß1), intercellular cell adhesion molecule-1 (ICAM-1) and nuclear factor-κB (NF-κB) were significantly decreased (P<0.05); and the expression of inhibitor of NF-κB (I-κB) was increased (P<0.05) through immunohistochemical and western blot. CONCLUSION: We studied the protective effects of baicalin against the lung and heart damage in experimental PAH rats; the therapeutic effects maybe through inhibiting vascular endothelial inflammatory response.

Involvement of IGF-1 and MEOX2 in PI3K/Akt1/2 and ERK1/2 pathways mediated proliferation and differentiation of perivascular adipocytes.

Perivascular adipocyte (PVAC) proliferation and differentiation were closely involved in cardiovascular disease. We aimed to investigate whether phosphatidylinositol 3-kinase (PI3K) and mitogen-activated protein kinase (MAPK) signaling pathways enhance PVAC functions activated by insulin-like growth factor 1(IGF-1) and suppressed by mesenchyme homeobox 2 (MEOX2). In this study, PVACs from primary culture were cultured and induced to differentiate. Cell viability assays demonstrated that IGF-1 promoted PVAC proliferation and differentiation. However MEOX2 counteracted these IGF-1-mediated actions. Flow Cytometry revealed that IGF-1 increased S phase cells and decreased apoptosis; however, MEOX2 decreased S phase cells, increased G0-G1 phase cells, and promoted apoptosis. During PVAC proliferation and differentiation, IGF-1 activated PI3K/Akt1/2 and ERK1/2 signaling pathways, upregulated the expression of these signaling proteins and FAS, and increased PVAC lipid content. In contrast, MEOX2 constrained the phosphorylation of ERK1/2 and Akt1/2 protein, down-regulated these signaling molecules and FAS, and decreased PVAC lipid content. Instead, MEOX2 knockdown enhanced the ERK1/2 and Akt1/2 phosphorylation, augmented the expression of these signaling molecules and FAS, and increased PVAC lipid content. Our findings suggested that PI3K/Akt1/2 and ERK1/2 activation mediated by IGF-1 is essential for PVAC proliferation and differentiation, and MEOX2 is a promising therapeutic gene to intervene in the signaling pathways and inhibit PVAC functions.

Bone marrow mesenchymal stem cells improve myocardial function in a swine model of acute myocardial infarction.

The aim of the current study was to confirm the effect and elucidate the mechanism of bone marrow mesenchymal stem cells (BMSCs) in acute myocardial infarction (AMI). AMI was induced in mini­swine by ligating the left anterior descending coronary artery, and BMSCs (1x107) were injected via a sterile microinjection into the ischemic area. Six months postoperatively, electrocardiograph­gated single photon emission computed tomography revealed that the myocardial filling defect was reduced and the left ventricular ejection fraction was improved in the BMSC group compared with the control group (P<0.05). Histopathological examination indicated that, in the BMSC treatment group, the percentage of survived myocardial tissue and the vessel density were increased, and the percentage of apoptosis was decreased compared with controls (P<0.05). Reverse transcription­polymerase chain reaction results indicated that the expression levels of multiple inflammatory factors were significantly upregulated in the BMSC group compared with levels in the control group (P<0.05). In conclusion, the present study demonstrated that BMSC injection significantly improved cardiac function and reduced infarct size in six months, indicating that this method may be valuable for future study in clinical trials.

Effect of cantharidins in chemotherapy for hepatoma: a retrospective cohort study.

This study aimed to evaluate the effects of cantharidins, a traditional Chinese medicine, in chemotherapy for the treatment of hepatoma. From August 2011 to December 2012, 96 patients with hepatoma, who were eligible for transcatheter hepatic arterial chemoembolization and received cantharidins, were selected for comparison with the control group of 95 patients without cantharidins. The treatment effect, clinical symptoms and adverse effects were analyzed. The results of the study showed that the cantharidins group had a higher overall efficient rate than the control group (p < 0.001). The improvement rate of the Karnofsky score in the cantharidins group was significantly higher than that of the control group (p = 0.014). In the cantharidins group, there was a decrease in white blood cell (WBC) count and gastrointestinal response rates were lower than those of the control group (p < 0.05). Therefore, the traditional Chinese medicine cantharidins showed effects of easing the progress of liver cancer, relieving side effects of chemotherapy and improving the quality of life in the treatment of hepatoma.

Proteomic profiling identified multiple short-lived members of the central proteome as the direct targets of the addicted oncogenes in cancer cells.

"Oncogene addiction" is an unexplained phenomenon in the area of cancer targeted therapy. In this study, we have tested a hypothesis that rapid apoptotic response of cancer cells following acute inhibition of the addicted oncogenes is because of loss of multiple short-lived proteins whose activity normally maintain cell survival by blocking caspase activation directly or indirectly. It was shown that rapid apoptotic response or acute apoptosis could be induced in both A431 and MiaPaCa-2 cells, and quick down-regulation of 17 proteins, which were all members of the central proteome of human cells, was found to be associated with the onset of acute apoptosis. Knockdown of PSMD11 could partially promote the occurrence of acute apoptosis in both MiaPaCa-2 and PANC-1 pancreatic cancer cells. These findings indicate that maintaining the stability of central proteome may be a primary mechanism for addicted oncogenes to maintain the survival of cancer cells through various signaling pathways, and quick loss of some of the short-lived members of the central proteome may be the direct reason for the rapid apoptotic response or acute apoptosis following acute inhibition of the addicted oncogenes in cancer cells. These findings we have presented can help us better understand the phenomenon of oncogene-addiction and may have important implications for the targeted therapy of cancer.

Long-term research of stem cells in monocrotaline-induced pulmonary arterial hypertension.

Our previous studies have shown that bone marrow mesenchymal stem cells (BMSCs) can inhibit the progression of pulmonary artery hypertension (PAH) in the monocrotaline (MCT) model in the short term. The aim of this study was to further investigate the long-term effect of BMSCs on PAH and to explore the mechanism of the protective effect including the pulmonary vascular remodeling and cell differentiation. PAH model was established by subcutaneous injection of 50 mg/kg MCT as previously study. Postoperatively, the animals were randomly divided into three groups (n = 10 in each group): control, PAH group, and BMSCs implantation group. Six months after injection, immunology and immunohistochemistry analysis indicated the MCT-induced intima-media thickness in muscular arteries was reduced (P < 0.05); the area of collagen fibers in lung tissue was lower (P < 0.05), and the proliferating cell nuclear antigen level in pulmonary artery smooth muscle cells was decreased (P < 0.05). Immunofluorescence showed that the cells have the ability to differentiate between von Willebrand factor and vascular endothelial growth factor. Six months after intravenous injection, BMSCs could significantly improve pulmonary function by inhibiting the ventricular remodeling and the effect of cell differentiation.

Baicalin protects the myocardium from reperfusion-induced damage in isolated rat hearts via the antioxidant and paracrine effect.

The aim of the present study was to investigate the protective effect of baicalin (BA) against ischemia-reperfusion (I/R) injury in isolated rat hearts. Sprague-Dawley rat hearts were rapidly removed, mounted on a Langendorff apparatus and subjected to 30 min ischemia followed by 30 min reperfusion with Krebs-Henseleit (K-H) solution at 37°C to establish the isolated I/R injury model. All animals (n=50) were randomly divided into five groups (n=10 in each): I, normal control; II, I/R; III, I/R plus 20 mg/kg BA; IV, I/R plus 40 mg/kg BA; and V, I/R plus 80 mg/kg BA. The degree of heart injury caused by the I/R was assessed by evaluating left ventricular function and by detecting the levels of lactate dehydrogenase (LDH) and creatine kinase (CK) in the coronary effluent and the myocardial superoxide dismutase (SOD) and malondialdehyde (MDA) levels in the isolated rat hearts. Myocardial infarct size and vascular density were assessed using histology and immunohistochemistry. The apoptotic cardiomyocytes were determined using flow cytometry (FCM). Compared with group II, the BA groups demonstrated improved left ventricular function, reduced CK and LDH release in the coronary effluent and increased SOD and MDA activity (P<0.05). Furthermore, histology and immunohistochemistry results showed that the infarct size was reduced and vessel density was augmented in the BA groups (P<0.01) compared with group II. The FCM results indicated that apoptosis was significantly lower in the BA groups than in group II (P<0.05) and that the protective effect was dose-dependent. In conclusion, these results demonstrated that BA exerts a dose-dependent protective effect on I/R injury in isolated rat hearts, the mechanisms of which may be associated with antioxidant and anti-apoptosis properties. To the best of our knowledge, this study is the first evaluation of the efficacy of BA in isolated rat hearts using histology and immunohistochemistry, providing a foundation for the use of BA in the treatment of acute myocardial infarction.

Differential shortening rate of telomere length in the development of human fetus.

Telomeres play an important role in the maintenance of genomic stability/integrity and are synthesized by the RNA-dependent polymerase telomerase. Progressive telomere shortening contributes to both in vitro and in vivo aging, and telomere length dynamics and telomerase expression profile in human tissues during extrauterine life have been well characterized. However, little is known about these changes in the early stage of gestation. In the present study, we determined telomere length and the expression of telomerase core units (telomerase reverse transcriptase, hTERT, and telomerase RNA component, hTERC) in human fetus tissues from 6 to 11 weeks of gestational age. A sharp decline in telomere length occurred between 6 and 7 weeks of gestational age, and a relatively stable or slightly shortened telomere length was thereafter maintained until birth. The inverse correlation between TERT or TERC expression and gestational age was steadily observed in these fetus tissues. Taken together, there is a rapid reduction followed by a slow erosion of telomere length in human fetus from gestational age 6-11 weeks, while hTERT and hTERC expression decreases steadily during this period. The present findings not only contribute to better understandings of telomere/telomerase biology in human embryonic development, but also are implicated in telomere/telomerase-related diseases or problems.