How much of the superolateral femoral neck should be removed in intramedullary nail fixation for intertrochanteric fracture?

The objective of this study was to measure how much of the superolateral femoral neck should be removed to reduce the incidence of wedge effect. Simulating surgery: Computed Tomography images of 131 intertrochanteric fracture patients were included, three-dimensionally reconstructed, virtually reduced and implanted with Proximal Femoral Nail Antirotation blade-Ⅱ(PFNA-Ⅱ) nail. The antero-posterior length and media-lateral width of the intersection between superolateral femoral neck and PFNA-Ⅱ nail were measured. Retrospective study: The pre- and postoperative CT of 30 patients were collected. The average varus angle of the neck-shaft angle and the correlation between the angles and the difference in the actual and estimated width of the fragments removed were measured. Models of 108 patient were selected for analysis. The average antero-posterior length and media-lateral width were 14.46 mm (14.00-14.93 mm) and 9.33 mm (8.79-9.87 mm), respectively. The AO/OTA classification was not significantly associated with the outcome, but the gender was. In the retrospective study, the mean value of the varus angles was -4.58° (SE = 6.85°), and the difference of width was strongly positively correlated with the varus angle with a correlation coefficient of 0.698. Results obtained in this study can improve the understanding of this region and help surgeons to make appropriate preoperative planning to reduce the incidence of wedge effect. Retrospective study provided effective proof of the reliability of this study.

Overview of the preparation method, structure and function, and application of natural peptides and polypeptides.

Natural polypeptides, a kind of molecular polymer with obvious biological activity, are widely existing in nature. They participate in various physiological activities of living organisms and play an important role in promoting human health. They are also widely applied in medicine, food, and cosmetic industries. By searching literature from Pubmed, Google Scholar, Web of Science, Springer Link and Elsevier, this work presents an overview of the preparation methods, the relationship between structure and function, and the application of natural polypeptides. The preparation methods mainly include solvent extraction, enzymatic decomposition, microbiological fermentation, chemical synthesis, genetic engineering recombination, and using cell free system. Natural polypeptide's physiological function mainly includes antioxidative, antibacterial, antihypertensive. This review could provide scientific basis for the research and development of natural polypeptide.

Fatal left atrial air embolism as a complication of percutaneous transthoracic lung biopsy: A case report.

BACKGROUND: Computed tomography (CT)-guided percutaneous lung biopsy is a common protocol in the context of diagnostic thoracic oncology, but entails a risk of complications including systematic air embolism (SAE). While SAE is often well tolerated, it can be difficult to treat and may result in rapid mortality in some cases. CASE SUMMARY: We report a rare case of left atrial SAE in a 71-year-old woman who underwent a CT-guided lung biopsy of a pulmonary nodule in the posterior basal segment of the right lower lobe. Shortly following needle extraction, she experienced a mild cough, hemoptysis, rapid-onset unconsciousness, and cardiopulmonary arrest. Cardiopulmonary resuscitation was immediately performed, but the patient died 40 min after the procedure. A closer review of collected CT scans revealed the presence of a large volume of air within the left atrium. CONCLUSION: Although SAE is generally well tolerated and asymptomatic, interventional radiologists must be aware of the risk of fatal outcomes and establish appropriate emergency management protocols. In this report, the characteristics, mechanisms, and treatment recommendations associated with SAE are discussed in an effort to improve the survival of affected patients.

Alantolactone ameliorates cancer cachexia-associated muscle atrophy mainly by inhibiting the STAT3 signaling pathway.

BACKGROUND: Cancer cachexia is a serious metabolic disorder syndrome that is responsible for the deaths of approximately 30% of patients with cancer, but effective drugs for cancer cachexia are still lacking. Inflammatory cytokines such as TNF-α or IL-6 are involved in the induction of skeletal muscle atrophy and fat depletion in patients with cancer cachexia. PURPOSE: In this study, we assessed the therapeutic effects of the natural compound alantolactone (AL) on cancer cachexia and tried to clarify the mechanisms by which it ameliorates muscle atrophy. METHODS: The C26 tumor-bearing cancer cachexia mouse model was used to evaluate the efficacy of AL in alleviating cancer cachexia in vivo. The levels of IL-6 or TNF-α in mouse serum were detected using ELISA kits. Cultured C2C12 myotubes and 3T3-L1 adipocytes treated with conditioned medium of C26 tumor cells, IL-6 or TNF-α were employed as in vitro cancer cachexia models to examine the effects of AL in vitro. RESULTS: AL (5 or 10 mg/kg, qd, i.p.) protected mice with C26 tumors and cachexia from a loss of body weight and muscle wasting but only slightly ameliorated fat loss. The circulating level of IL-6 but not TNF-α was significantly decreased by AL. AL treatment significantly inhibited STAT3 activation in the gastrocnemius (GAS) muscle of cancer cachexia mice. AL (0.125, 0.25, 0.5 and 1 µM) dose-dependently ameliorated myotube atrophy and STAT3 activation in cultured C2C12 myotubes induced by conditioned medium from C26 tumor cells. AL also ameliorated C2C12 myotube atrophy induced by IL-6 and inhibited IL-6-mediated STAT3 activation. AL exhibited weak effects on ameliorating TNF-α-mediated myotube atrophy and NF-κB activation. Only AL at high doses of more than 5 µM ameliorated lipolysis and STAT3 activation induced in mature 3T3-L1 adipocytes by conditioned medium from C26 tumor cells. CONCLUSIONS: AL significantly ameliorated muscle atrophy in a cancer cachexia model mainly through the inhibition of the STAT3 pathway. AL might be a promising lead compound in the development of drug candidates for cancer cachexia therapy.

Grade G2 Rectal Neuroendocrine Tumor Is Much More Invasive Compared With G1 Tumor.

BACKGROUND: To compare clinicopathologic feature of rectal neuroendocrine tumor (NET) grade G1 with G2 NET. METHODS: Six hundred-one cases of rectal G1 and G2 NETs diagnosed in our center were analyzed. RESULTS: Of 601 cases of rectal NET, 515 cases were with grade G1 and 86 cases were with grade G2. Median tumor size was 0.7 cm. Compared with G1 NET, G2 tumors were with significantly larger tumor size (0.8 vs 2.2 cm, p < 0.001), less percentages of patients with tumors confined to submucosa (92.6 vs 42.8%, p < 0.001), more frequent presence of microvascular invasion (MVI) (3.6 vs 16.9%, p < 0.001) or peri-neural invasion (PNI) (2.0 vs 24.1%, p < 0.001). Incidence of lymph node and distant metastasis was 5.2 and 2.1% in G1 NET compared with 44.2 and 31.4% in G2 tumor, respectively (p < 0.001). For tumors sized 1-2 cm and confined to submucosa, incidence of lymph node metastasis was 6.1% for G1 NET compared with 21.1% for G2 NET. Status of MVI/PNI was predictive of lymph node metastasis for G2 tumor rather than G1 NET in this subgroup. CONCLUSIONS: Rectal G2 NET was much more invasive with significantly elevated prevalence of lymph node metastasis compared with G1 tumor.

Chronic myelomonocytic leukemia-associated pulmonary alveolar proteinosis: A case report and review of literature.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare condition that can cause progressive symptoms including dyspnea, cough and respiratory insufficiency. Secondary PAP is generally associated with hematological malignancies including chronic myelomonocytic leukemia (CMML). To the best of our knowledge, this is the first reported case of PAP occurring secondary to CMML. CASE SUMMARY: We report the case of a 63-year-old male who presented with a recurrent cough and gradually progressive dyspnea in the absence of fever. Based upon clinical symptoms, computed tomography findings, bone marrow aspiration, flow cytometry studies and cytogenetic analyses, the patient was diagnosed with PAP secondary to CMML. He underwent whole lung lavage in March 2016 to alleviate his dyspnea, after which he began combined chemotherapeutic treatment with decitabine and cytarabine. The patient died in January 2020 as a consequence of severe pulmonary infection. CONCLUSION: This case offers insight regarding the mechanistic basis for PAP secondary to CMML and highlights potential risk factors.

Acute myeloid leukemia during pregnancy: a single institutional experience with 17 patients and literature review.

Management of acute myeloid leukemia during pregnancy (P-AML) is a challenging endeavor with limited evidence-based information available. To truly achieve the goal of improving P-AML patients, additional evidence-based research is necessary. We retrospectively reviewed cases of 17 patients diagnosed with P-AML, including seven for acute promyelocytic leukemia (APL) from January 2012 to June 2019. Among the non-APL, 90% patients (9/10) ended pregnancy prior to induction chemotherapy. The median intervals between diagnosis and start of chemotherapy were 5 days (range 1-14 days). Four patients elected to delay chemotherapy by more than one week. Of the seven APL patients, six received all-trans retinoic acid (ATRA) before the diagnostic molecular results. Five patients underwent cesarean sections (CS) and all newborns were alive (four preterm and one full-term deliveries). Overall, approximately 94% of the patients (16/17) are currently alive in remission. To treat P-AML patients in a safer manner, balancing the risk of progressing to advanced disease and proceeding with pregnancy is required. We consider a slight delay (less than 14 days) in the termination of pregnancy may not differ the prognosis to patients with non-APL. For APL, patients will benefit from prompt administration of ATRA for highly suspected cases.

SiBaoChongCao exhibited anti-fatigue activities and ameliorated cancer cachexia in mice.

SiBaoChongCao (SBCC) is a functional food product containing fermentation of Acremonium terricola belonging to the Cordyceps genus. SBCC at 1 and 2 g kg-1 for 20 days exhibited anti-fatigue activities such as increasing exhaustive swimming and running time of mice and increasing the strength of muscle. The increased muscle endurance in SBCC-treated mice might be related to enhancement of muscle cell growth and differentiation and improvement of muscle response to exercise training, as shown by an increase in muscle cross-sectional area and elevation of MHC, MyoD, MyoG and PGC-1α levels. And, SBCC at 1.5 g kg-1 could ameliorate cancer-related cachexia such as ameliorating decrease in body temperature and inhibiting fat tissue atrophy. The anti-cachexia effects of SBCC might be related to inhibition of inflammatory cytokine IL-6 secretion and suppression of over-lipolysis and lipid over-utilization through inhibiting the activation of AMPK and p38 MAPK and down-regulating the level of UCP1.

Very Early Colorectal Anastomotic Leakage within 5 Post-operative Days: a More Severe Subtype Needs Relaparatomy.

Early anastomotic leakage (AL), usually defined as leakage within 30 post-operative days, represents a severe entity. However, mounting evidence has indicated that majorities of leakage occur within one week after surgery, making late AL rarity. Here we analyzed 101 consecutive colorectal AL, all of which occurred within 30 post-operative days, during Jan 2013 and Dec 2015 in cancer hospital of Fudan University. AL occurring within 5 post-operative days was defined as very early AL (vE-AL). We evaluated risk factors of vE-AL compared with non-vEAL and correlated with post-leakage peritonitis and need of relaparatomy. We found that AL occurred at median time of 7 days after surgery. 23 cases were vE-AL. Reconstruction of post-peritoneum for mid-low rectal carcinoma significantly reduced incidence of vE-AL compared with non-vE-AL (p = 0.042). Patients with vE-AL was associated with presence of peritonitis (p = 0.031), the latter significantly correlated with increased re-operation rate (p = 6.8E-13). Besides, patients with vE-AL trended to correlate with increased re-operation rate after leakage (p = 0.088). In concludsion, vE-AL occurring within 5 post-operative days represents a severe subtype associated with general peritonitis and need of relaparatomy.

Down-regulation of sirtuin 3 is associated with poor prognosis in hepatocellular carcinoma after resection.

BACKGROUND: Sirtuin 3 (Sirt3), one of the seven Sirtuins family members, plays critical roles in the progression of multiple cancer types. However, its role in the prognosis of hepatocellular carcinoma (HCC) has not yet been investigated systematically. METHODS: The correlation of Sirtuins expression with prognosis of HCC was determined by immunohistochemistry (IHC) in a large HCC patient cohort (n = 342). Expression of Sirt3 in tumoral and peritumoral tissues of HCC patients were further determined by western blotting (WB). RESULTS: IHC and WB studies both showed a decreased expression of Sirt3 in tumoral tissues compared with peritumoral tissues (P = 0.003 for IHC, P = 0.0042 for WB). Decreased expression of Sirt3 in both tumoral and peritumoral tissues was associated with increased recurrence probability and decreased overall survival rate by univariate analyses (intratumoral Sirt3: P = 0.011 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.017 for TTR, P = 0.023 for OS), the prognostic value was strengthened by multivariate analyses (intratumoral Sirt3: P = 0.031 for TTR, P = 0.001 for OS; peritumoral Sirt3: P = 0.047 for TTR, P = 0.031 for OS). Intratumoral Sirt3 also showed a favorable prognostic value in patients with BCLC stage A (TTR, P = 0.011; OS, P < 0.001). In addition, we found that IHC studies of other sirtuin members showed a decreased expression of Sirt2, Sirt4 and Sirt5 and an increased expression of Sirt1, Sirt6 and Sirt7 in intratumoral tissues compared with peritumoral tissues. In contrast to Sirt3, other members did not showed a remarkable correlation with HCC prognosis. CONCLUSIONS: Down-regulation of intratumoral and peritumoral Sirt3 were both associated with poor outcome in HCC, moreover, intratumoral Sirt3 was a favorable prognostic predictor in early stage patients.

Decreased expression of GATA2 promoted proliferation, migration and invasion of HepG2 in vitro and correlated with poor prognosis of hepatocellular carcinoma.

BACKGROUND: GATA family of transcription factors are critical for organ development and associated with progression of various cancer types. However, their expression patterns and prognostic values for hepatocellular carcinoma (HCC) are still largely unknown. METHODS: Expression of GATA transcription factors in HCC cell lines and tissues (n = 240) were evaluated by RT-qPCR, western blot and immunohistochemistry. Cellular proliferation, migration and invasion of HepG2 was evaluated by CCK-8 kit, scratch wound assay and transwell matrigel invasion assay, respectively. RESULTS: GATA2 expression was decreased in HCC cell lines (p = 0.056 for mRNA, p = 0.040 for protein) and tissues (p = 1.27E-25) compared with normal hepatocytes. Decreased expression of intratumoral GATA2 protein significantly correlated with elevated alpha feto-protein (p = 2.7E-05), tumor size >5 cm (p = 0.049), absence of tumor capsule (p = 0.002), poor differentiation (p = 0.005), presence of tumor thrombi (p = 0.005) and advanced TNM stage (p = 0.001) and was associated with increased recurrence rate and decreased overall survival rate by univariate (p = 1.6E-04 for TTR, p = 1.7E-04 for OS) and multivariate analyses (HR = 0.63, 95% CI = 0.43-0.90, p = 0.012 for TTR; HR = 0.67, 95% CI = 0.47-0.95, p = 0.026 for OS). RNAi-mediated knockdown of GATA2 expression significantly enhanced proliferation, migration and invasion of HepG2 cell in vitro. CONCLUSIONS: Decreased expression of hematopoietic factor GATA2 was associated with poor prognosis of HCC following resection.

Combination of intratumoral invariant natural killer T cells and interferon-gamma is associated with prognosis of hepatocellular carcinoma after curative resection.

PURPOSE: To investigate the prognostic value of intratumoral invariant natural killer T (iNKT) cells and interferon-gamma (IFN-γ) in hepatocellular carcinoma (HCC) after curative resection. EXPERIMENTAL DESIGN: Expression of TRAV10, encoding the Vα24 domain of iNKT cells, and IFN-γ mRNA were assessed by quantitative real-time polymerase chain reaction in tumor from 224 HCC patients undergoing curative resection. The prognostic value of these two and other clinicopathologic factors was evaluated. RESULTS: Either intratumoral iNKT cells and IFN-γ alone or their combination was an independent prognostic factor for OS (P = 0.001) and RFS (P = 0.001) by multivariate Cox proportional hazards analysis. Patients with concurrent low levels of iNKT cells and IFN-γ had a hazard ratio (HR) of 2.784 for OS and 2.673 for RFS. The areas under the curve of iNKT cells, IFN-γand their combination were 0.618 vs 0.608 vs 0.654 for death and 0.591 vs 0.604 vs 0.633 for recurrence respectively by receiver operating characteristic curve analysis. The prognosis was the worst for HCC patients with concurrent low levels of iNKT cells and IFN-γ, which might be related with more advanced pTNM stage and more vascular invasion. CONCLUSIONS: Combination of intratumoral iNKT cells and IFN-γ is a promising independent predictor for recurrence and survival in HCC, which has a better power to predict HCC patients' outcome compared with intratumoral iNKT cells or IFN-γ alone.

The clinical and prognostic implications of pluripotent stem cell gene expression in hepatocellular carcinoma.

Recently, growing evidence has demonstrated that aberrant expression of pluripotent stem cell-related genes may confer primitive and aggressive traits and be associated with unfavorable clinical outcomes in certain solid cancers. However, the role of pluripotent stem cell gene expression in hepatocellular carcinoma (HCC) remains unexplored. We evaluated the expression of the pluri potent stem cell genes Oct4, Sox2 and Klf4, as well as that of the c-Myc, Nanog and Lin28 genes in HCC samples and corresponding adjacent non-tumor liver samples obtained from 57 patients using quantitative real-time reverse transcription-PCR (qRT-PCR). The results revealed that six pluripotent stem cell gene expression levels were upregulated in the tumor tissues compared with the corresponding adjacent non-tumor liver tissues. In HCC tissues, aberrant expression of Sox2 and Lin28 was associated with a large tumor size (P=0.02 and P=0.03, respectively), while increased expression levels of c-Myc (P=0.01) were correlated with vascular invasion. Moreover, high Klf4 expression levels were associated with aggressive tumor behaviors in terms of vascular invasion (P=0.02) and poor tumor differentiation (P=0.03). Survival analysis revealed that Klf4 expression was independently associated with overall survival [OS; hazard ratio (HR), 8.61; 95% confidential interval (CI), 2.7-27.5; P<0.001] and recurrence-free survival (RFS; HR, 3.96; 95% CI, 1.3-11.6; P=0.01). In conclusion, pluripotent stem cell genes are associated with HCC progression and a poor prognosis. The development of therapeutic strategies, including adjuvant therapy, that take cancer stem cell (CSC)-related markers into consideration is likely to be a key factor in further improvements of the prognosis of HCC patients undergoing curative liver resection.

Intratumoral regulatory T cells with higher prevalence and more suppressive activity in hepatocellular carcinoma patients.

BACKGROUND AND AIM: Regulatory T cells (Treg) play a vital role in immunosuppressive crosstalk; however, Tregs from different locations lead to different clinical outcomes. Our aim was, therefore, to compare the prevalences and suppressive phenotypes of Tregs in the peripheral blood, peritumor, and intratumor of patients with hepatocellular carcinoma (HCC). METHODS : The frequencies and phenotypes of CD4(+) CD25(+) CD127(low/-) CD49d(-) Tregs in the periphery, peritumor, and intratumor of 78 HCC patients and 12 healthy controls were evaluated by flow cytometry. Treg-cell suppressive activity was determined using an in vitro CD154 expression assay. Tregs from tumor and paired peritumor were then hybridized using an Agilent whole genome oligo microarray, and selected genes were validated by real-time polymerase chain reaction. Functional analysis of the microarray data was performed using Kyoto Encyclopedia of Genes and Genomes and Gene Ontology analyses. RESULTS : Intratumoral Tregs exhibited higher frequencies and more suppressive phenotypic functions than those in peritumor and periphery, whereas there was no difference between the latter two. Functional analysis showed that complement cascades, p53, and glycosylphosphatidylinositol-anchor biosynthesis pathways were significantly upregulated in intratumoral Tregs; the salivary secretion pathway was significantly downregulated in intratumoral Tregs, and immune cells and tumor-immuno-related Gene Ontology terms were significantly affected. CONCLUSIONS : Tregs in different locations exhibited different functional statuses. A higher prevalence and more suppressive phenotype suggested a critical role for intratumoral Tregs in the formation of multicellular immunosuppressive networks. HCC immunotherapy may be improved, therefore, by specific locational Tregs elimination or suppression.

The functional impairment of HCC-infiltrating γδ T cells, partially mediated by regulatory T cells in a TGFß- and IL-10-dependent manner.

BACKGROUND & AIMS: The immunosuppressive network within the tumor microenvironment is one of the major obstacles to the success of cancer immunotherapy. γδ T cells are attractive effectors for cancer immunotherapy. Nevertheless, the promising anti-tumor effect in vitro is partially if not totally mitigated in vivo. Thus, understanding the immune status of tumor-infiltrating γδ T cells is essential for orchestrating effective immunotherapy strategies. In this study, we have investigated the immunophenotype and function of γδ T cells in hepatocellular carcinoma (HCC) patients. METHODS: The phenotype of γδ T cells in peripheral blood, and peritumoral and tumoral tissues of HCC patients (n=61) was characterized by flow cytometry. Functional analysis of the HCC-infiltrating γδ T cells was conducted directly after γδ T cell isolation. RESULTS: The infiltration of γδ T cells in tumoral tissues was significantly reduced compared to paired peritumoral tissues. Impairment in degranulation of the granule pathway and downregulation of IFN-γ secretion were also demonstrated in HCC-infiltrating γδ T cells, which was in agreement with the results of gene microarray analysis, and further strengthened by the compromised specific cytotoxicity and IFN-γ secretion in vitro. Moreover, isolated HCC-infiltrating CD4(+)CD25(+) regulatory T cells (Treg cells) directly suppressed the cytotoxic function and IFN-γ secretion of γδ T cells in a TGFß- and IL-10-dependent manner. CONCLUSIONS: The effector function of γδ T cells was substantially impaired in HCC, which is partially mediated by Treg cells. We propose a new mechanism by which immune privilege develops within the tumor milieu.

ß-Asarone inhibits neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in an in vitro model and AßPP/PS1 mice.

ß-Asarone, an active component of the Acori graminei rhizome that has been used as traditional Chinese herb, has been reported to be capable of inhibiting neuronal apoptosis. However, the signaling mechanism underlying the inhibitory effect of ß-asarone has remained elusive. This study was aimed to investigate whether the CaMKII signaling pathway is involved in the ß-asarone mediated neuroprotection. Using PC12 cells and primary cultures of cortical neurons treated with amyloid-ß (Aß)(1-40) or Aß(1-42) peptide, we demonstrated that ß-asarone can protect PC12 cells and cortical neurons and inhibit neuronal apoptosis by activating the CaMKII-α/p-CREB/Bcl-2 pathway. Moreover, CaMKII-α overexpression enhanced the ß-asarone-induced p-CREB-Bcl-2 expression and anti-apoptotic effects. Interestingly, suppression of CaMKII-α by siRNA or a specific inhibitor can significantly reduce the ß-asarone-induced p-CREB and Bcl-2 expression and Aß(1-40) induced neuronal apoptosis in PC12 cells. AßPP/PS1 mice at the age of 3 months and age-matched wild-type mice were intragastrically administered ß-asarone (7 mg/kg/day, 21 mg/kg/day) or a vehicle daily for 4 months. ß-asarone improved cognitive function of the AßPP/PS1 mice and reduced neuronal apoptosis in the cortex of the AßPP/PS1 mice. A significant increase in CaMKII/CREB/Bcl-2 expression was observed in the cortex of the AßPP/PS1 mice treated with ß-asarone. In summary, our observations demonstrated that ß-asarone can inhibit neuronal apoptosis via the CaMKII/CREB/Bcl-2 signaling pathway in in vitro models and in AßPP/PS1 mice. Therefore, ß-asarone can be used as a potential therapeutic agent in the long-term treatment of Alzheimer's disease.

Interferon regulatory factor (IRF)-1 and IRF-2 are associated with prognosis and tumor invasion in HCC.

BACKGROUND: Interferon regulatory factor (IRF)-1 and IRF-2 are transcriptional factors that mediate interferons functions; the loss of IRF-1 expression and gain of IRF-2 expression were associated with malignant phenotype in multiple cancers. However, their roles in the progression of hepatocellular carcinoma (HCC) remain poorly described. METHODS: Immunohistochemistry was used to analyze the nuclear expression of IRF-1/2 in a cohort of 332 HCC patients. The expression of IRF-1/2 in HCC cell lines with stepwise metastasis potential was determined by immunoblotting. Downregulation of IRF-1 or IRF-2 expression was mediated by shRNAs; a series of experiments were conducted to determine the changes of invasion ability and downstream molecular events. RESULTS: High expression of IRF-1 was associated with good outcome (p<.001 for OS/TTR), while high expression of IRF-2 was relevant to increased recurrence probability (p=.049) in HCC patients. The combination of the 2 IRFs showed better predictive power than either factor alone. Immunoblotting analysis revealed that IRF-2/IRF-1 ratio was positively correlated with the metastatic potential in human HCC cell lines. Downregulation of IRF-2 led to sharply attenuated invasion ability, paralleled with a decreased expression of STAT3, p-STAT3(Ser727), and MMP9. While downregulation of IRF-1 caused a concurrent decrease in IRF-2, little or no change was displayed in IRF-2/IRF-1 ratio, invasion ability, and MMP9 expression. CONCLUSIONS: IRF-1 and IRF-2 expression were associated with prognosis of HCC patients with opposite predictive power. IRF-2/IRF-1 ratio was associated with tumor invasion, probably through modulation of MMP9 expression mediated by STAT3.

Muscone exerts neuroprotection in an experimental model of stroke via inhibition of the fas pathway.

Identifying small molecules that are neuroprotective against stroke injury will be highly beneficial for treatment therapies. A cell viability assay and gas chromatography-mass spectrometry were used to identify active small molecules in XingNaoJing, which is a well known Chinese medicine prescribed for the effective treatment of stroke. Studies have found that muscone is the active compound that prevents PC12 cell and cortical neuron damage following various injuries. Analysis of apoptosis indicated that muscone inhibited glutamate-induced apoptotic cell death of PC12 cells and cortical neurons. Fas and caspase-8 expression were upregulated following glutamate treatment in cortical neurons, and was markedly attenuated in the presence of muscone. Furthermore, muscone significantly reduced cerebral infarct volume, neurological dysfunction and inhibited cortical neuron apoptosis in middle cerebral artery occluded (MCAO) rats in a dose-dependent manner. Moreover, a significant decrease in Fas and caspase-8 expression in the rat cortex was observed in MCAO rats treated with muscone. Our results demonstrate that muscone may be a small active molecule with neuroprotective properties, and that inhibition of apoptosis and Fas is an important mechanism of neuroprotection by muscone. These findings suggest a potential therapeutic role for muscone in the treatment of stroke.

Targeting of the Sonic Hedgehog pathway by atractylenolides promotes chondrogenic differentiation of mesenchymal stem cells.

Molecules that enhance chondrogenic differentiation in mesenchymal stem cells (MSCs) were identified and isolated using an in vitro Gli reporter gene assay in MSCs incorporating a Sonic Hedgehog (Shh) target. Atractylenolide III, which promoted Gli1-mediated transcriptional activity, was isolated from an ethyl acetate extract of the Rhizoma, Atractylodis macrocephalae. After dehydration, atractylenolide III was transformed to atractylenolide I. Both atractylenolides were confirmed by MS, UV, IR, 1H- and 13C-NMR spectra. Atractylenolide III (which contains -OH at the 8-position) and atractylenolide I (which lacks -OH at the 8-position) were found to effectively promote the activity of the Gli promoter. While the hydroxyl group of atractylenolide III was not essential for the effect of atractylenolide, its effect was dependent on Shh signaling. Phenotypic cellular analysis indicated that atractylenolides induced MSCs to differentiate into chondrocytes, as shown by increased expression of specific chondrogenic markers including collagen II, aggrecan and the cartilage related transcription factor, Sox9. Atractylenolides significantly increased the expression of Shh and its target gene Gli-1, indicating that Shh signaling was activated by atractylenolides. Moreover, inhibition of Shh signaling reduced the effect of atractylenolides on the chondrogenic phenotype. The discovery that atractylenolides induce chondrocytes from MSCs is promising for bony disease therapy.

Expression of TREM-1 in hepatic stellate cells and prognostic value in hepatitis B-related hepatocellular carcinoma.

Hepatocellular carcinoma (HCC) is a typical inflammation-related malignancy characterized by high postoperative recurrence and metastasis. Although several inflammatory cells and inflammatory signatures have been linked to poor prognosis, the inflammation-associated molecular mechanisms of HCC development and progression are largely unknown. Here we show that triggering receptor expressed in myeloid cells (TREM)-1, a transmembrane receptor expressing in myeloid cells, was also expressed in tumor-activated hepatic stellate cells (HSCs) and associated with the aggressive behavior of HCC cells. Enzyme-linked immunosorbent assay was used to measure the expression levels of soluble TREM-1 (sTREM-1) in activated hepatic stellate cells supernatant and 92 preoperative and postoperative plasmas of patients with malignancy and/or benign liver tumor/disease, respectively. Expression levels of TREM-1 were assessed by immunohistochemistry in tissue microarray from 240 patients with HCC. As a result, increased secretion of sTREM-1 from activated HSCs was observed after co-culture with HCC cell lines (P < 0.001), and conditioned medium collected from activated HSCs/cancer associated myofibroblasts (CAMFs) with or without agonist/inhibitor of TREM-1 significantly changed the migratory ability of HCC cells. The levels of sTREM-1 were significantly higher in patients with HCC than those with benign liver tumors (P < 0.005). Peritumoral density of TREM-1 was shown to be an independent prognosis predictor according to univariate (P < 0.001 for both overall survival and time to recurrence) and multivariate analysis (P = 0.008 for overall survival; P = 0.005 for time to recurrence). Thus, these observations suggest that TREM-1 is related to the aggressive tumor behavior and has potential value as a prognostic factor for HCC.