Serum pro-surfactant protein B is correlated with clinical properties in osteosarcoma patients.

It is critical to find efficient non-invasive prognostic factor for osteosarcoma. In this study, we demonstrated that serum protein of pro-surfactant protein B (pro-SFTPB) may be a potential diagnostic indicator in osteosarcoma. We found that serum pro-SFTPB was highly expressed in osteosarcoma patients and presented good diagnostic value to discern osteosarcoma patients from non-osteosarcoma control subjects. Serum pro-SFTPB was also significantly correlated with advanced clinical stage, distant metastasis, and shorter overall survival. In addition, serum pro-SFTPB was demonstrated to be an independent prognostic factor for osteosarcoma. Overall, our study demonstrated that serum pro-SFTPB may be a useful diagnostic factor for osteosarcoma.

The hidden blood loss and its factors in patients undergoing minimally invasive knee arthroscopy.

Background: With respect to knee arthroscopy, assessing the amount of hidden blood loss is of great importance to avoid potential complications such as fever, anemia, difficulty in wound healing and wound infection. The current study aims to investigate the hidden blood loss and its factors in patients who underwent minimally invasive knee arthroscopy. Methods: Consecutive patients with knee joint injury, who underwent arthroscopic minimally invasive treatment, were enrolled from January 2019 to November 2020 and were retrospectively studied. Demographic information on these patients, such as medical history and biochemical parameters, was collected. The hidden blood loss was calculated. Multivariate linear regression analysis was used to confirm independent factors associated with hidden blood loss. Results: Finally, a total of 100 patients aged 44.78 ± 13.67 (range 17-66) years were reviewed, and it was found that a substantial amount of [387.02 ± 252.56 (range 18.89-1130.06) ml] hidden blood loss occurred after minimally invasive knee arthroscopy. Univariate analysis showed that this hidden blood loss was negatively correlated with age, gender, postoperative hemoglobin, and postoperative hematocrit (all P < 0.05), while it was positively correlated with body mass index (BMI), length of hospital stay, preoperative red blood cells, preoperative hemoglobin, preoperative hematocrit, blood volume, and the presence of medical conditions (all P < 0.05). Further multivariate linear regression indicated that preoperative hematocrit, blood volume, and postoperative hematocrit were independent factors associated with actual blood loss, and preoperative hematocrit, blood volume, postoperative hematocrit, and gender were independent factors associated with hidden blood loss, respectively (all P < 0.05). Conclusion: Preoperative hematocrit, preoperative blood volume, postoperative hematocrit, and gender are the influencing factors of hidden blood loss in patients undergoing minimally invasive treatment under knee arthroscopy. More attention should be paid to hidden blood loss and its factors during the perioperative period.

Synthesis, anticancer evaluation and mechanism studies of novel indolequinone derivatives of ursolic acid.

A series of novel indolequinone derivatives of ursolic acid bearing ester, hydrazide, or amide moieties were designed, synthesized, and screened for their in vitro antiproliferative activities against three cancer cell lines (MCF-7, HeLa, and HepG2) and a normal gastric mucosal cell line (Ges-1). A number of compounds showed significant activity against tested cancer cell lines. Among them, compound 6t exhibited the most potent activity against three cancer cell lines with IC50 values of 1.66 ± 0.21, 3.16 ± 0.24, and 10.35 ± 1.63 µM, respectively, and considerably lower cytotoxicity to Ges-1 cells. Especially, compound 6t could arrest cell cycle at S phase, suppress the migration of MCF-7 cells, elevate intracellular reactive oxygen species (ROS) level, and decrease mitochondrial membrane potential. Western blot analysis showed that compound 6t upregulated Bax, cleaved caspase-3/9, cleaved PARP levels and downregulated Bcl-2 level of MCF-7 cells. All these results indicated that compound 6t could significantly induce the apoptosis of MCF-7 cells. Meanwhile, compound 6t markedly decreased p-AKT and p-mTOR expression, which revealed that compound 6t probably exerted its cytotoxicity through targeting PI3K/AKT/mTOR signaling pathway. Therefore, compound 6t could be a promising lead for the discovery of novel anticancer agents.

In vitro and in vivo evaluation of a ciprofloxacin delivery system based on poly(DLLA-co-GA-co-CL) for treatment of chronic osteomyelitis.

Chronic osteomyelitis causes serious injury to patients. Antibiotic delivery systems based on poly(lactide-co-glycolide) (PLGA) have great potential for treatment of chronic osteomyelitis. However, PLGA has a glass-transition temperature that is higher than physiological temperatures, resulting in a lack of flexibility for implantation into the bone marrow cavity. As an alternative, poly(d, l-lactide-co-glycolide-co-ε-caprolactone) (PLGC) presents good flexibility due to the introduction of poly(ε-caprolactone) segments. To develop a new strategy for treatment of chronic osteomyelitis, a ciprofloxacin delivery system was prepared using PLGC as carriers, the antibacterial effects of which were evaluated both in vivo and in vitro. The in vitro release behavior showed that the average release reached 268.5 µg/days on day 33, with a cumulative release rate of 56.01%. A bacteriostatic ring, with a diameter of 26.83 ± 0.83 mm, was produced by ciprofloxacin against Staphylococcus aureus after 30 days of release via our ciprofloxacin-PLGC system. After 4 weeks of treatment in vivo, chronic-osteomyelitis-model rats had a bodyweight of 385.83 ± 17.23 g and a normal white-blood-cell count, as well as a lower number of bacterial colonies per gram of bone tissue of (10.6 ± 3.0) × 101 CFU/g. Furthermore, no inflammatory cells were observed via hematoxylin-and-eosin staining, and normal bone structure was observed via X-ray. Taken together, our findings indicate that our novel ciprofloxacin-PLGC system yielded noteworthy antibacterial effects both in vitro and in vivo, suggesting that it may be useful for treating patients with chronic osteomyelitis.

Design, Synthesis, and Anticancer Evaluation of Novel Indole Derivatives of Ursolic Acid as Potential Topoisomerase II Inhibitors.

In this study, a series of new indole derivatives of ursolic acid bearing different N-(aminoalkyl)carboxamide side chains were designed, synthesized, and evaluated for their in vitro cytotoxic activities against two human hepatocarcinoma cell lines (SMMC-7721 and HepG2) and normal hepatocyte cell line (LO2) via MTT assay. Among them, compound 5f exhibited the most potent activity against SMMC-7721 and HepG2 cells with IC50 values of 0.56 ± 0.08 µM and 0.91 ± 0.13 µM, respectively, and substantially lower cytotoxicity to LO2 cells. A follow-up enzyme inhibition assay and molecular docking study indicated that compound 5f can significantly inhibit the activity of Topoisomerase IIα. Further mechanistic studies performed in SMMC-7721 cells revealed that compound 5f can elevate the intracellular ROS levels, decrease mitochondrial membrane potential, and finally lead to the apoptosis of SMMC-7721 cells. Collectively, compound 5f is a promising Topoisomerase II (Topo II) inhibitor, which exhibited the potential as a lead compound for the discovery of novel anticancer agents.

Synthesis and biological evaluation of novel N-(piperazin-1-yl)alkyl-1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid as potential MEK inhibitors.

In this paper, a series of novel 1H-dibenzo[a,c]carbazole derivatives of dehydroabietic acid bearing different N-(piperazin-1-yl)alkyl side chains were designed, synthesised and evaluated for their in vitro anticancer activities against three human hepatocarcinoma cell lines (SMMC-7721, HepG2 and Hep3B). Among them, compound 10g exhibited the most potent activity against three cancer cell lines with IC50 values of 1.39 ± 0.13, 0.51 ± 0.09 and 0.73 ± 0.08 µM, respectively. In the kinase inhibition assay, compound 10g could significantly inhibit MEK1 kinase activity with IC50 of 0.11 ± 0.02 µM, which was confirmed by western blot analysis and molecular docking study. In addition, compound 10g could elevate the intracellular ROS levels, decrease mitochondrial membrane potential, destroy the cell membrane integrity, and finally lead to the oncosis and apoptosis of HepG2 cells. Therefore, compound 10g could be a potent MEK inhibitor and a promising anticancer agent worthy of further investigations.

Design, synthesis, and anticancer evaluation of novel quinoline derivatives of ursolic acid with hydrazide, oxadiazole, and thiadiazole moieties as potent MEK inhibitors.

In this article, a series of novel quinoline derivatives of ursolic acid (UA) bearing hydrazide, oxadiazole, or thiadiazole moieties were designed, synthesised, and screened for their in vitro antiproliferative activities against three cancer cell lines (MDA-MB-231, HeLa, and SMMC-7721). A number of compounds showed significant activity against at least one cell line. Among them, compound 4d exhibited the most potent activity against three cancer cell lines with IC50 values of 0.12 ± 0.01, 0.08 ± 0.01, and 0.34 ± 0.03 µM, respectively. In particular, compound 4d could induce the apoptosis of HeLa cells, arrest cell cycle at the G0/G1 phase, elevate intracellular reactive oxygen species level, and decrease mitochondrial membrane potential. In addition, compound 4d could significantly inhibit MEK1 kinase activity and impede Ras/Raf/MEK/ERK transduction pathway. Therefore, compound 4d may be a potential anticancer agent and a promising lead worthy of further investigation.

Chloroquine increases phosphorylation of AMPK and Akt in myotubes.

AIMS: There are reports that ataxia telangiectasia mutated (ATM) can activate the AMP-activated protein kinase (AMPK) and also Akt, two kinases that play integral parts in cardioprotection and metabolic function. We hypothesized that chloroquine and resveratrol, both known ATM activators, would also activate AMPK and Akt. MAIN METHODS: Phosphorylation of AMPK and Akt was assessed after C2C12 myotubes were exposed to chloroquine or resveratrol. Additional experiments were done in cells expressing shRNA against ATM or in the presence of the ATM inhibitor KU55933. The effects of chloroquine on intracellular calcium were assessed with the fluorescent probe Calcium Green-1 AM. KEY FINDINGS: 0.5 mM chloroquine increased AMPK phosphorylation by nearly 4-fold (P<0.05), and 0.25 mM chloroquine roughly doubled Akt phosphorylation (P<0.05). Chloroquine also increased autophosphorylation of ATM by ~50% (P<0.05). Resveratrol (0.15 mM) increased AMPK phosphorylation about three-fold (P<0.05) but in contrast to chloroquine sharply decreased Akt phosphorylation. Chloroquine increased AMPK and Akt phosphorylation in myotubes expressing shRNA against ATM that reduced ATM protein levels by about 90%. Likewise, chloroquine-stimulated phosphorylation of AMPK and Akt and resveratrol-stimulated phosphorylation of AMPK were not altered by inhibition of ATM. Chloroquine decreased intracellular calcium by >50% concomitant with a decrease in glucose transport. SIGNIFICANCE: These ATM-independent effects of chloroquine on AMPK and Akt and the additional effect to decrease intracellular calcium are likely to partially underlie the positive metabolic effects of chloroquine that have been reported in the literature.

Effects of cyclopamine on the proliferation and apoptosis of LNCaP cells and expression of the PCA3 gene in human prostate cancer / 中华男科学杂志

<p><b>OBJECTIVE</b>To explore the effects of cyclopamine on the proliferation and apoptosis of LNCaP cells and the expression of the PCA3 gene in human prostate cancer in vitro.</p><p><b>METHODS</b>LNCaP cells were treated with cyclopamine at the concentrations of 1, 5, 10 and 15 micromol/L for 24, 48 and 72 hours. The inhibitory effects of cyclopamine on the proliferation and apoptosis of the LNCaP cells were detected by MTT and flow cytometry respectively, the morphological changes of the cells observed by Hoechst 33258 staining, and the expression of the PCA3 gene determined by real-time fluorescence quantitative reverse transcriptase polymerase chain reaction (FQ-RT-PCR).</p><p><b>RESULTS</b>Compared with the blank control group, cyclopamine significantly inhibited the proliferation of the LNCaP cells at 5, 10 and 15 micromol/L (P <0.01), reaching IC50 at 10 micro mol/L at 48 hours. The apoptosis rates of the LNCaP cells at 24, 48 and 72 hours were 37.21%, 57.38% and 57.98% in the 10 micromol/L group and 21. 16% , 71.31% and 72.90% in the 15 micro.mol/L group, significantly different from those in the control (P <0. 01). The cell apoptosis showed a rising trend with the increase of cyclopamine concentration and acting-time, while the expression of the PCA3 gene was decreasing with the increased concentration of cyclopamine, significantly lower than that of the blank control group (P <0.01) , and extremely low in the 10 micromo/L group</p><p><b>CONCLUSION</b>Cyclopamine intervention at 10 and 15 micromol/L for 48 and 72 hours could significantly inhibit the at all time points. Proliferation and induce the apoptosis of LNCaP cells and reduce the expression level of PCA3.</p>

Opportunities for 2-18F Fluoro-2-Deoxy-D-Glucose PET/CT in Cervical-Vaginal Neuroendocrine Carcinoma: Case Series and Literature Review

OBJECTIVE: Neuroendocrine cervical carcinoma is a rare subtype of cervical cancer. These tumors exhibit an aggressive behavior with early regional lymph node and distant metastases. The purpose of our study was to describe five cases of neuroendocrine cervical-vaginal carcinoma and to discuss the potential of the 2-[18F] fluoro-2-deoxy-D-glucose positron emission tomography/computed tomography (18F-FDG PET/CT) scan for the detection of this rare malignancy. MATERIALS AND METHODS: Five cases of cervical-vaginal neuroendocrine tumor were retrospectively collected, during a two year (from September 2009 to August 2011) period in our hospital. The clinical staging distributions were International Federation of Gynecology and Obstetrics (FIGO) stage IB2 (1 of 5), stage IIA (3 of 5) and stage IVA (1 of 5). RESULTS: Two cases (cases 1 and 4) were restaged after 18F-FDG PET/CT scan in the initial staging process. Post-treatment 18F-FDG PET/CT scans, in three patients, revealed positive findings for tumor recurrence or lymph node metastases. Two patients (cases 2 and 3) died of tumor within two years. CONCLUSION: 18F-FDG PET/CT scan is a useful tool in cervical-vaginal neuroendocrine tumor. In its initial staging, the 18F-FDG PET/CT scan may help assess the possible nodal involvement or early hematogeneous spreading. We can also use the 18F-FDG PET/CT to detect local recurrence and to evaluate the treatment response after clinical manipulation.