Effect of traditional Chinese medicine in osteosarcoma: Cross-interference of signaling pathways and potential therapeutic targets.

Osteosarcoma (OS) has a high recurrence rate, disability rate, mortality and metastasis, it brings great economic burden and psychological pressure to patients, and then seriously affects the quality of life of patients. At present, the treatment methods of OS mainly include radiotherapy, chemotherapy, surgical therapy and neoadjuvant chemotherapy combined with limb salvage surgery. These treatment methods can relieve the clinical symptoms of patients to a certain extent, and also effectively reduce the disability rate, mortality and recurrence rate of OS patients. However, because metastasis of tumor cells leads to new complications, and OS cells become resistant with prolonged drug intervention, which reduces the sensitivity of OS cells to drugs, these treatments still have some limitations. More and more studies have shown that traditional Chinese medicine (TCM) has the characteristics of "multiple targets and multiple pathways," and can play an important role in the development of OS through several key signaling pathways, including PI3K/AKT, Wnt/ß-catenin, tyrosine kinase/transcription factor 3 (JAK/STAT3), Notch, transforming growth factor-ß (TGF-ß)/Smad, nuclear transcription factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), nuclear factor E2-related factor 2 (Nrf2), Hippo/YAP, OPG/RANK/RANKL, Hedgehog and so on. In this paper, the signaling pathways of cross-interference between active ingredients of TCM and OS were reviewed, and the development status of novel OS treatment was analyzed. The active ingredients in TCM can provide therapeutic benefits to patients by targeting the activity of signaling pathways. In addition, potential strategies for targeted therapy of OS by using ferroptosis were discussed. We hope to provide a unique insight for the in-depth research and clinical application of TCM in the fields of OS growth, metastasis and chemotherapy resistance by understanding the signaling crosstalk between active ingredients in TCM and OS.

An insight into the key genes and biological functions associated with insulin resistance in adipose tissue with microarray technology.

In the present study, the key genes and biological functions associated with insulin resistance were investigated by comparing the gene expression profiles of adipose tissue obtained from insulin­sensitive and insulin­resistant patients. The gene expression data set GSE20950 was downloaded from the Gene Expression Omnibus, including 39 adipose tissue samples obtained from insulin­sensitive and insulin­resistant patients undergoing gastric bypass surgery. Adipose samples were divided into two groups (the insulin­sensitive and insulin­resistant groups) and the differentially expressed genes (DEGs) were screened out with packages of R. The interactions among DEGs were retrieved with Osprey and functional enrichment analysis was performed with the WebGestalt system. Information regarding the interaction network and enriched biological functions was combined to construct a functional interaction network. Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis was then conducted using the Database for Annotation, Visualization and Integrated Discovery. A total of 170 DEGs were detected in the insulin­sensitive group, 8 downregulated and 162 upregulated. Response to glucose stimulus was the most significantly over­represented functional term. The focal adhesion pathway was identified to be significant in the genes of the functional interaction network. The present study revealed key biological functions and DEGs in adipose tissues associated with insulin resistance, which may facilitate the development of novel therapies for insulin resistance and diabetes.

Effect of caspase-9 inhibition on endoplasmic reticulum stress induced cortical neuronal injury in rats.

Our study investigated the apoptotic mechanism of rat cortical neurons following hypoxia/reperfusion induced endoplasmic reticulum stress (ERS) in vitro and to explore the effect of caspase-9 inhibition on ERS induced apoptosis. Cortical neurons were collected from neonatal rats and cultured in vitro. Immunohistochemistry and immunofluorescence staining for neuron-specific enolase (NSE) were performed to determine the purity of neurons. AnnexinV/PI staining followed by flow cytometry was employed to detect apoptosis rate. Fluorescein isothiocyanate (FITC) staining was done to measure the expression of caspase-3 and -9. Western blot assay was carried out to measure the protein expression of caspase-12, glucose-regulated protein (GRP) 78 and Cytochrome C. The cortical neurons from neonatal rats could be purified and cultured in vitro. In the in vitro hypoxia/reperfusion of cortical neurons (hypoxia for 6 h and reperfusion for 24 h and 48 h), the protein expression of GRP78, caspase-3, 9 and 12 was markedly increased (P < 0.01). Following pre-treatment with caspase-9 inhibitor, the number of apoptotic cells was significantly reduced following hypoxia for 6 and reperfusion for 24 h or 48 h (P < 0.05). Moreover, the expression of caspse-3 and 12 and GRP78 was also significantly reduced in the presence of caspase-9 inhibitor treatment (P < 0.05), but the release of Cytochrome C remained unchanged (P > 0.05). These results demonstrated that ERS is involved in the neuronal apoptosis following in vitro hypoxia/reperfusion, and caspase-9 inhibition can depress the ERS induced apoptosis of neurons.

Association of lipoprotein-associated phospholipase A2 with characteristics of vulnerable coronary atherosclerotic plaques.

PURPOSE: Lipoprotein-associated phospholipase A2 (Lp-PLA2) is an inflammatory enzyme expressed in atherosclerotic plaques. We investigated the association of circulating Lp-PLA2 with characteristics of vulnerable coronary atherosclerotic plaques. MATERIALS AND METHODS: We recruited 113 patients with either unstable angina (UA, n=59) and stable angina (SA, n=54) by coronary angiography. Thirty-six healthy subjects served as controls. Intravascular ultrasound (IVUS) was used to evaluate the characteristics of coronary atherosclerotic plaque, and serum Lp-PLA2 concentration was measured as well. RESULTS: Lp-PLA2 concentration was significantly higher in both UA and SA patients [(396±36) µg/L and (321±39) µg/L, respectively] compared with the controls [(127 ± 49) µg/L, p<0.01], and higher in UA than SA group. IVUS findings showed that remodeling index (RI) (0.91 ± 0.15 vs. 0.85 ± 0.11, p=0.005) and eccentricity index (EI) (0.73 ± 0.16 vs. 0.65 ± 0.22, p=0.039) were larger in UA than in SA group, and fibrous caps were thicker in SA than UA group [(0.91 ± 0.23) mm vs. (0.63 ± 0.21) mm, p=0.032]. Moreover, Lp-PLA2 correlated positively with EI (r=0.439, p<0.01) and RI (r=0.592, p<0.05) in UA group. There was an inverse relationship between Lp-PLA2 and fibrous cap thickness in both UA (r=-0.587, p<0.001) and SA (r=-0.318, p<0.05) groups. The independent risk factors in UA group were Lp-PLA2 (OR=1.055, 95% CI: 1.03-1.08, p=0.013), LDL-cholesterol (OR=0.032, 95% CI: 0.00-0.05, p=0.041) and fibrous cap thickness (OR=0.008, 95% CI: 0.00-0.45, p=0.019). Lp-PLA2 was strongly associated with both EI and fibrous cap thickness in both groups. CONCLUSION: Serum level of Lp-PLA2 is associated with both eccentricity index and fibrous cap thickness in both UA and SA groups. Elevated levels of circulating Lp-PLA2 might to be a strong risk factor and more serious for unstable angina than stable angina.

[Investigations and analysis of traumatic condition of Longnan area in Wenchuan earthquake].

OBJECTIVE: To investigate and analyze the traumatic conditions of Longnan area of Gansu in Wenchuan earthquake, and to explore the measures coping with unexpected disasters. METHODS: A sample survey including questionnaire survey, interviews and other methods was adopted to investigate the conditions of affected population of Longnan area in earthquake, especially on the traumatic conditions, the injured causes, treatment methods. RESULTS: In the sample survey of a total of 1652 earthquake casualties, the dead were 16 and the patients with extremities fractures were 750 (45.4%). Organized and timely rescue of the wounded could reduce the complications and the mortality . CONCLUSION: Strengthening the prevention and treatment of earthquake trauma can effectively decrease the death rate and disabled rate.

[Clinical comparison between micro-endoscopic discectomy (MED) and open discectomy for treatment of lumbar disc herniation].

OBJECTIVE: To compare between micro-endoscopic discectom) (MED) and open decompression discectomy, and assess the clinical value of MED. METHODS: Two hundreds and sixty-one cases who suffered from lumbar disc herniation had a retrospective study. One hundred and twenty-one of 261 patients were treated with MED including 72 male and 52 female with an average age of 37.6 years ranging 26 to 63, the segment of herniated discs were at L4.5 in 66 and at L5S1 in 58. The other 137 patients were treated with decompression by fenestration and discectomy including 66 male and 71 female with an average age of 44.5 years ranging 25 to 71, the segment of herniated discs were at L4.5 in 64 and at L5S1 in 73. MED was performed via a scopes. Open decompression discectomy was performed decompression by fenestration and discectomy. RESULTS: MED group were followed up for 14.5 months on average, the operative time was (85 +/- 15) minutes and blood loss was (50 +/- 10) ml, time of laying in bed after operation was (50 +/- 8) hours. Open decompression group were followed up for 15.5 months on average, operative time was (60 +/- 15) minutes and blood loss was (80 +/- 20) ml, time of laying bed after operation was (150 +/- 24) hours. MED group needed significantly less narcotic medication after operation than open decompression group. According to modified Macnab criteria, the results were excellent in 94, good in 25, fair in 5 in MED group and excellent in 101, good in 28, fair in 8 in open decompression group. CONCLUSION: As compared with open decompression group, MED offers a similar short-term clinical outcome, but with smaller incision, less tissue trauma and quicker recovery.

[Morphometry of osteoclasts in experimental fracture healing of rabbits].

This study was designed to investigate the effects of some Traditional Chinese Medicine (TCM) agents on bone resorption and morphometric features of osteoclasts as well as their relationships. TCM ShengGuZaiZaoSan and XianLingGuBao, were used to treat the experimental fracture. Thirty 6-month-old Chinchilla rabbits were used for the establishment of animal models each with a 3 mm bone defect in the middle of left radius as well as of right radius. These models were divided randomly into 3 groups : ShengGuZaiZaoSan Group (Group A), XianLingGuBao groups (Group B) and control-group (Group C). Every group was further divided into 2 subgroups: a former sacrificed group (14 days after operation) and a latter sacrificed group (31 days after operation). After the rabbits being killed, the samples of their undecalcified calli were subjected to the morphometry study of bone resorption and osteoclasts. Group A had more bone resorption, compared with Group B and C. Both Groups A and B exhibited some changed morphometric features of osteoclasts as compared with Group C (P < 0.05). Simple correlation analysis indicated that bone resorption is mainly correlated with osteoclast numbers, and that in individual group, bone resorption is correlated with osteoclast form factor, area and mean photodensity (P < 0.05). These allow us to conclude that ShengGuZaiZaoSan can increase bone resorption and accelerate bone remodeling by increasing osteoclast numbers at the former stage and can enhance osteoclast function at the latter stage. These changes are beneficial to fracture healing.

[Experimental study on effect of shengguzaizaosan on rabbits fracture healing].

OBJECTIVE: To study the effect of shengguzaizaosan on experimental fracture healing. METHODS: Thirty six-month-old Chinchilla rabbits were made the models with 3 mm bone defect in the middle of two-side radius and were divided randomly into 3 groups: shengguzaizaosan group (group A, n = 10), xianlinggubao group (group B, n = 10) and control group (group C, n = 10). Five rabbits were sacrificed 14 days and 31 days after operation respectively. The double marks with tetracyslin hydrochloride were given on the 4th day and the 5th day for the first mark and on the 11th day and the 12th day for the second mark in the rabbits sacrificed 14 days later, and on the 20th day and the 21st day for the first mark and on the 28th day and the 29th day for the second mark in the rabbits sacrificed 31 days later. The samples were taken to make the bone histomorphometry study. RESULTS: When compared group A with group C, there were significant differences (P<0.01) in osteoid area density, osteoid mean width, active osteoblastic surface, mineralization surface and dynamic parameters after 14 days, and in mean width of mineralization callus, active osteoblastic surface and mean depth of lacunae after 31 days. There was a approximate effect between group B and group C. when compared group B with group A, there were significant differences (P<0.05) in osteoclastic index, mineralization surface, bone formation rate after 14 days, and in osteoid surface, mean depth of lacunae and bone formation rate after 31 days. CONCLUSION: Shengguzaizaosan can increase osteoid, accelerate mineralization rate and bone formation rate, and reduce mineralization lag time at early period of fracture. It can increase mineralization callus width and resorption of osteoclast at later period of fracture. To some extent, shengguzaizaosan can accelerate the experimental fracture healing.