Hyperendogenous Heparinization Suggests a Guideline for the Management of Massive Wasp Stings in Two Victims.

Bees and wasps (order Hymenoptera) are commonly encountered worldwide and often deliver defensive stings when in contact with humans. Massive envenomation resulting from >50 stings causes a toxic reaction and life-threatening complications that typically result in rhabdomyolysis and disseminated intravascular coagulation. Two male patients who were stung over 80 times by wasps experienced severe coagulation abnormality. Consecutive examination by thromboelastography (TEG) guided by heparinase treatment during their hospitalization evidenced heparin-like coagulation dysfunction despite no clinical use of heparin-like substances. Numerous tests were also conducted to confirm whether the coagulation abnormalities could be attributed to hyperendogenous heparinization and allergic reaction, rhabdomyolysis, and vascular endothelial cell injury without apparent disseminated intravascular coagulation, which might all be affected by the production of endogenous heparin. The reduced coagulation potential caused by hyperendogenous heparinization was associated with the binding of antithrombin and the activation of fibrinolysis. In addition, TEG-identified coagulopathy was moderated using protamine for heparin neutralization. The massively envenomed patients survived and were discharged after completion of medical care. We also review clinical manifestations from other published case reports, including topical treatment. Our study provides clinical evidence and guidance for diagnosis via TEG and appropriate intervention with protamine for patients with massive wasp envenomation.

Doxorubicin metabolism moderately attributes to putative toxicity in prodigiosin/doxorubicin synergism in vitro cells.

Doxorubicin (Dox) is a widely neoplasm chemotherapeutic drug with high incidences of cardiotoxicity. Prodigiosin (PG), a red bacterial pigment from Serratia marcescens, has been demonstrated to potentiate Dox's cytotoxicity against oral squamous cell carcinoma cells through elevating Dox influx and identified as a Dox enhancer via PG-induced autophagy; however, toxicity of normal cell remains unclear. This study is conducted to evaluate putative cytotoxicity features of PG/Dox synergism in the liver, kidney, and heart cells and further elucidate whether PG augmented Dox's effect via modulating Dox metabolism in normal cells. Murine hepatocytes FL83B, cardio-myoblast h9c2, and human kidney epithelial cells HK-2 were sequentially treated with PG and Dox by measuring cell viability, cell death characteristics, oxidative stress, Dox flux, and Dox metabolism. PG could slightly significant increase Dox cytotoxicity in all tested normal cells whose toxic alteration was less than that of oral squamous carcinoma cells. The augmentation of Dox cytotoxicity might be attributed to the increase of Dox-mediated ROS accumulation that might cause slight reduction of Dox influx and reduction of Dox metabolism. It was noteworthy to notice that sustained cytotoxicity appeared in normal cells after PG and Dox were removed. Taken together, moderately metabolic reduction of Dox might be ascribed to the mechanism of increase Dox cytotoxicity in PG-induced normal cells; nevertheless, the determination of PG/Dox dose with sustained cytotoxicity in normal cells needs to be comprehensively considered.

Autologous Chondrocyte Implantation Versus Microfracture in the Knee: A Meta-analysis and Systematic Review.

PURPOSE: To compare clinical outcomes among patients with fractures of knee cartilage who were treated with autologous chondrocyte implantation (ACI) or microfracture (MF). METHODS: A systematic review was made of randomized controlled trials of articular cartilage lesions of the knee treated with ACI or MF that were published between January 2000 and November 2018 and catalogued in 4 major databases. The outcomes of clinical score, quality of life (QoL), pain relief score, and failure rate were assessed. RESULTS: A final group of 12 randomized controlled trials were included that enrolled a total of 659 patients with knee cartilage lesions: 332 patients had received ACI and 327 patients had undergone MF. Patients ranged in age from 25 to 41 years, and the majority were male. Lesion size ranged from 2.3 to 10.0 cm2. Pooled analysis found no significant difference in the improvement in International Knee Documentation Committee and Lysholm scores or overall Knee Injury and Osteoarthritis Outcome Score measures between patients in the ACI and MF groups at 1-year, 2-year, and 5-year follow-up examinations or in failure rate at 2-year, 3-year, and 5-year follow-up timepoints. However, patients treated with ACI had a significant benefit in activities of daily living at follow-up of 5 years or less compared with patients treated with MF. ACI treatment also showed better improvement in QoL and pain relief than MF at 5-year and 2-year follow-up examinations, respectively. CONCLUSIONS: The pooled analysis found no significant difference in the improvement in International Knee Documentation Committee or Lysholm scores or overall Knee Injury and Osteoarthritis Outcome Score measures between patients in the ACI and MF groups at 1 to 5 years of follow-up. Patients treated with ACI may have a significant benefit in activities of daily living, QoL, and pain relief compared with patients treated with MF, although clinical relevance may not be achieved. LEVEL OF EVIDENCE: Level II, systematic review of Level I and II investigations.

In Silico Prediction of Intestinal Permeability by Hierarchical Support Vector Regression.

The vast majority of marketed drugs are orally administrated. As such, drug absorption is one of the important drug metabolism and pharmacokinetics parameters that should be assessed in the process of drug discovery and development. A nonlinear quantitative structure-activity relationship (QSAR) model was constructed in this investigation using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to render the extremely complicated relationships between descriptors and intestinal permeability that can take place through various passive diffusion and carrier-mediated active transport routes. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 53, r2 = 0.93, q CV 2 = 0.84, RMSE = 0.17, s = 0.08), test set (n = 13, q2 = 0.75-0.89, RMSE = 0.26, s = 0.14), and even outlier set (n = 8, q2 = 0.78-0.92, RMSE = 0.19, s = 0.09). The built HSVR model consistently met the most stringent criteria when subjected to various statistical assessments. A mock test also assured the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

Innate-immune responses of tilapia (Oreochromis mossambicus) exposure to acute cold stress.

In this present study, Oreochromis mossambicus tilapia were transferred to cold water at 12°C for various time intervals (1, 4, 8, 24, and 48 hr) and its innate immune response was analyzed by studying cellular and humoral parameters. In vivo, alternative complement pathway activity in blood plasma was rapidly increased at 1 hr of cold water (12°C) exposure. Lysozyme activity and cortisol levels of plasma were increased at 4 and 1 hr, respectively. Surprisingly, only plasma cortisol levels remained unchanged through 24 hr of cold water transfer. Phagocytic ability, phagocytic capacity, and respiratory burst (RB) activity of head kidney (HK) leukocytes and splenocytes showed no any significant changes. In peripheral blood leukocytes, phagocytic capacity, and RB activity were increased at 24 hr of cold water exposure. The expressions of genes involved innate immunity in splenocytes and HK leukocytes of tilapia cold water exposure were analyzed, messenger RNA (mRNA) expressions of HSP70, HSP90, and immunoglobulin M failed to change upon exposure to cold stress. Major histocompatibility complex-I and II mRNAs were significantly increased in tilapia splenocytes at 1 hr of cold water transferred. Whereas myxovirus (Mx) expression was increased in splenocytes and HK leukocytes of tilapia after 1 hr of cold water exposed. Our result reveals that the exposure of tilapia to acute cold stress condition significantly enhances plasma acid phosphatase activity and both phagocytic capacity and RB activity. Furthermore, cold stress significantly stimulates Mx gene expression in splenocytes and HK leukocytes.

Polyalthia Clerodane Diterpene Potentiates Hypoglycemia via Inhibition of Dipeptidyl Peptidase 4.

Serine protease dipeptidyl peptidase 4 (DPP-4) is involved in self/non-self-recognition and insulin sensitivity. DPP-4 inhibitors are conventional choices for diabetic treatment; however, side effects such as headache, bronchus infection, and nasopharyngitis might affect the daily lives of diabetic patients. Notably, natural compounds are believed to have a similar efficacy with lower adverse effects. This study aimed to validate the DPP-4 inhibitory activity of clerodane diterpene 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) from Polyalthia longifolia, rutin, quercetin, and berberine, previously selected through molecular docking. The inhibitory potency of natural DPP-4 candidates was further determined by enzymatic, in vitro Caco-2, and ERK/PKA activation in myocyte and pancreatic cells. The hypoglycemic efficacy of the natural compounds was consecutively analyzed by single-dose and multiple-dose administration in diet-induced obese diabetic mice. All the natural-compounds could directly inhibit DPP-4 activity in enzymatic assay and Caco-2 inhibition assay, and HCD showed the highest inhibition of the compounds. HCD down-regulated LPS-induced ERK phosphorylation in myocyte but blocked GLP-1 induced PKA expression. For in vivo tests, HCD showed hypoglycemic efficacy only in single-dose administration. After 28-days administration, HCD exhibited hypolipidemic and hepatoprotective efficacy. These results revealed that HCD performed potential antidiabetic activity via inhibition of single-dose and long-term administrations, and could be a new prospective anti-diabetic drug candidate.

In Silico Prediction of PAMPA Effective Permeability Using a Two-QSAR Approach.

Oral administration is the preferred and predominant route of choice for medication. As such, drug absorption is one of critical drug metabolism and pharmacokinetics (DM/PK) parameters that should be taken into consideration in the process of drug discovery and development. The cell-free in vitro parallel artificial membrane permeability assay (PAMPA) has been adopted as the primary screening to assess the passive diffusion of compounds in the practical applications. A classical quantitative structure-activity relationship (QSAR) model and a machine learning (ML)-based QSAR model were derived using the partial least square (PLS) scheme and hierarchical support vector regression (HSVR) scheme to elucidate the underlying passive diffusion mechanism and to predict the PAMPA effective permeability, respectively, in this study. It was observed that HSVR executed better than PLS as manifested by the predictions of the samples in the training set, test set, and outlier set as well as various statistical assessments. When applied to the mock test, which was designated to mimic real challenges, HSVR also showed better predictive performance. PLS, conversely, cannot cover some mechanistically interpretable relationships between descriptors and permeability. Accordingly, the synergy of predictive HSVR and interpretable PLS models can be greatly useful in facilitating drug discovery and development by predicting passive diffusion.

Plantago asiatica Seed Extracts Alleviated Blood Pressure in Phase I⁻Spontaneous Hypertension Rats.

Arterial pressure of each new breeding spontaneous Phase-1 hypertension (P1-HT) rat was recorded for 5 min by intravascular femoral artery catheter that served as a reference value prior to treatment. In the acute antihypertensive test, 0.36 g/kg Bwt of Plantago asiatica seed extract (PSE) was administered, via gavage feeding, to P1-HT rats, and the arterial pressures were continuously recorded for 1 h. The acute antihypertensive effects of PSE on P1-HT rats appeared within 15 min after PSE administration and lasted over 1 h with systolic pressure decreased 31.5 mmHg and diastolic pressure decreased 18.5 mmHg. The systolic pressure decreased 28 mmHg and diastolic pressure decreased 16 mmHg in P1-HT rats when simultaneously compared with verapamil hydrochloride (reference drug), whereas there were no significant differences in the pretreated reference values of acute PSE treatment and the untreated control. In the chronic test, P1-HT rats received 0.36 g/kg Bwt day of PSE or equal volume of water for 4 weeks via oral gavage, and the lower blood pressure tendencies of chronic PSE treatment were also found when compared with the controls. The antihypertensive values of PSE were also confirmed in spontaneously hypertensive rats (SHRs). Oral administration with PSE can effectively moderate blood pressure within an hour, while taking PSE daily can control the severity of hypertension, suggesting PSE is a potentially antihypertensive herb.

Antrodia Cinnamomea Prolongs Survival in a Patient with Small Cell Lung Cancer.

Introduction: Antrodia cinnamomea (AC) is an extremely rare medicinal fungus native to forested regions of Taiwan. It possesses numerous biological activities, especially anti-tumor effects shown in various in vitro cancer cells and in vivo animal models. However, there are few clinical reports about AC as a treatment for cancer patients. This report attempts to demonstrate the therapeutic effect of dish-cultured AC (DAC) on a small cell lung cancer (SCLC) patient taken orally for an extended duration. Patient concerns: An 88-year-old male with a history of diabetes mellitus and hypertension visited the outpatient department with the symptoms of dyspnea and a cough for two weeks. After a diagnosis of SCLC, the patient declined both chemotherapy and radiotherapy because of the side effects and only accepted supportive care without additional therapy. Diagnosis: Limited-stage SCLC (T4N2M1a, stage IV) after the chest radiograph, computed tomography-guided biopsy, and pathological diagnosis. Interventions: The patient was prescribed DAC with an increasing dosage, from 5 g/d up to 10 g/d DAC, for six months, without radiation or chemotherapy treatment. Outcomes: DAC caused the tumor to shrink substantially. Surprisingly, the patient survived for 32 months without relapse after six months of DAC treatment. Laboratory examinations indicated that the patient's health had improved significantly, reverting to near normal levels. Notably, he had a good quality of life with a high Barthel index score. Unfortunately, this patient died of septic shock caused by acute cholangitis. Conclusion: DAC may exert an anti-cancer effect, which can lead to tumor regression. This is supposed to be achieved by the combined DAC's immunomodulatory, anti-angiogenic, anti-metastatic, anti-proliferative, and pro-apoptotic effects mediated through multiple signaling pathways. We propose that DAC can be used as a complementary medicine to prolong the life expectancy and improve the life quality of SCLC patients.

Effects of Sting Plant Extracts as Penetration Enhancers on Transdermal Delivery of Hypoglycemic Compounds.

Background and objectives: The percutaneous route is an interesting and inventive investigation field of drug delivery. However, it is challenging for drug molecules to pass through the skins surface, which is a characterized by its permeability barrier. The purpose of this study is to look at the effect of some penetration enhancers on in vivo permeation of insulin and insulin sensitizers (curcumin and rutin) through diabetes-induced mouse skin. Materials and Methods: Sting crude extracts of Dendrocnide meyeniana, Urtica thunbergiana Sieb. and Zucc, and Alocasia odora (Lodd.) Spach were used as the penetration enhancers. Mouse skin irritation was tested by smearing the enhancers for the measurements at different time points and the cell viability of the HaCaT human skin keratinocytes, which was determined by Trypan blue exclusion and MTT assays to evaluate human biosafety for these extracts after the mouse skin permeation experiments. Results: All enhancers induced a slight erythema without edema on the mouse skin that completely recovered after 6 h from the enhancer smears as compared with normal mouse skin. Furthermore, no damaged cells were found in the HaCaT keratinocytes under sting crude extract treatments. The blood sugar level in the diabetic mice treated with the insulin or insulin sensitizers, decreased significantly (p < 0.05) in the presence of enhancers. The area under the curve (AUC) values of transdermal drug delivery (TDD) ranged from 42,000 ± 5000 mg/dL x min without enhancers, to 30,000 ± 2000 mg/dL x min in the presence of enhancers. Conclusions: This study exhibited that natural plant extracts could be preferred over the chemically synthesized molecules and are safe and potent penetration enhancers for stimulating the transdermal absorption of drugs.

Insight Analysis of Promiscuous Estrogen Receptor α-Ligand Binding by a Novel Machine Learning Scheme.

Estrogen receptor α (ERα) plays a significant role in occurrence of breast cancer and may cause various adverse side-effects when ERα is an off-target protein. A theoretical model was derived to predict the binding affinity of ERα using the pharmacophore ensemble/support vector machine (PhE/SVM) scheme to consider the promiscuous characteristic of ERα. The estimations by PhE/SVM were discovered to be in good agreement with the observed values for those training molecules ( n = 31, r2 = 0.80, qCV2 = 0.77, RMSE = 0.57, s = 0.58), test molecules ( n = 179, q2 = 0.91-0.96, RMSE = 0.33, s = 0.26) and outliers ( n = 15, q2 = 0.80-0.86, RMSE = 0.56, s = 0.49). When subjected to various statistical validations, the PhE/SVM model consistently fulfilled the strictest criteria. A mock test also asserted its predictivity. When compared with crystal structures, the calculated results are consistent with the reported ERα-ligand co-complex structure, and the plasticity nature of ERα is also disclosed. Consequently, this precise, fast, and robust model can be adopted to predict ERα-ligand binding affinities and to design safer non-ERα-targeted pharmaceuticals in the process of drug discovery and development.

Theoretical Prediction of the Complex P-Glycoprotein Substrate Efflux Based on the Novel Hierarchical Support Vector Regression Scheme.

P-glycoprotein (P-gp), a membrane-bound transporter, can eliminate xenobiotics by transporting them out of the cells or blood⁻brain barrier (BBB) at the expense of ATP hydrolysis. Thus, P-gp mediated efflux plays a pivotal role in altering the absorption and disposition of a wide range of substrates. Nevertheless, the mechanism of P-gp substrate efflux is rather complex since it can take place through active transport and passive permeability in addition to multiple P-gp substrate binding sites. A nonlinear quantitative structure⁻activity relationship (QSAR) model was developed in this study using the novel machine learning-based hierarchical support vector regression (HSVR) scheme to explore the perplexing relationships between descriptors and efflux ratio. The predictions by HSVR were found to be in good agreement with the observed values for the molecules in the training set (n = 50, r² = 0.96, qCV2 = 0.94, RMSE = 0.10, s = 0.10) and test set (n = 13, q² = 0.80⁻0.87, RMSE = 0.21, s = 0.22). When subjected to a variety of statistical validations, the developed HSVR model consistently met the most stringent criteria. A mock test also asserted the predictivity of HSVR. Consequently, this HSVR model can be adopted to facilitate drug discovery and development.

16-Hydroxycleroda-3,13-dien-15,16-olide and N-Methyl-Actinodaphine Potentiate Tamoxifen-Induced Cell Death in Breast Cancer.

In this study, we investigated whether 16-hydroxycleroda-3,13-dien-15,16-olide (HCD) and N-methyl-actinodaphine (MA) could sensitize breast cancer cells to Tamoxifen (TMX) treatment. MA or HCD alone or in combination with TMX dose-dependently inhibited MCF-7 and MDA-MB-231 cell growth, with a more potent inhibition on MDA-MB 231 cells. Furthermore, this novel combination significantly induced S and G2/M cell cycle phase in MDA-MB 231 than MCF-7 cells. Further determination of the apoptotic induction showed that MA or HCD and TMX combination inhibited MDA-MB-231 and MCF-7 cancer cells by upregulating Bax and by downregulating Bcl-2 mRNA and protein expression without altering Caspase-8 and Caspase-12 expression. These results suggest that MA or HCD pretreatment may potentiate the anti-tumor effect of tamoxifen on breast cancer.

Neuroprotective Role of Phytochemicals.

Neurodegenerative diseases are normally distinguished as disorders with loss of neurons. Various compounds are being tested to treat neurodegenerative diseases (NDs) but they possess solitary symptomatic advantages with numerous side effects. Accumulative studies have been conducted to validate the benefit of phytochemicals to treat neurodegenerative diseases including Alzheimer's disease (AD) and Parkinson's disease (PD). In this present review we explored the potential efficacy of phytochemicals such as epigallocatechin-3-galate, berberin, curcumin, resveratrol, quercetin and limonoids against the most common NDs, including Alzheimer's disease (AD) and Parkinson's disease (PD). The beneficial potentials of these phytochemicals have been demonstrated by evidence-based but more extensive investigation needs to be conducted for reducing the progression of AD and PD.

FAK and S6K1 Inhibitor, Neferine, Dually Induces Autophagy and Apoptosis in Human Neuroblastoma Cells.

Human neuroblastoma cancer is the most typical extracranial solid tumor. Yet, new remedial treatment therapies are demanded to overcome its sluggish survival rate. Neferine, isolated from the lotus embryos, inhibits the proliferation of various cancer cells. This study aimed to evaluate the anti-cancer activity of neferine in IMR32 human neuroblastoma cells and to expose the concealable molecular mechanisms. IMR32 cells were treated with different concentrations of neferine, followed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay to assess cell viability. In an effort to determine the molecular mechanisms in neferine-incubated IMR32 cells, cell cycle arrest, cell migration, and focal adhesion kinase (FAK), the 70-kDa ribosomal S6 kinase 1 (S6K1), poly (ADP-ribose) polymerase (PARP), caspase-3, Beclin-1, and microtubule-associated protein 1A/1B-light chain 3 (LC3) protein expressions were investigated. Neferine strongly disrupted the neuroblastoma cell growth via induction of G2/M phase arrest. Furthermore, neferine provoked autophagy and apoptosis in IMR32 cells, confirmed by p-FAK, and p-S6K1 reduction, LC3-II accumulation, Beclin-1 overexpression, and cleaved caspase-3/PARP improvement. Finally, neferine markedly retarded cell migration of neuroblastoma cancer cells. As a result, our findings for the first time showed an explicit anti-cancer effect of neferine in IMR32 cells, suggesting that neferine might be a potential candidate against human neuroblastoma cells to improve clinical outcomes with further in vivo investigation.

Hypoglycemic Efficacy of Docking Selected Natural Compounds against α-Glucosidase and α-Amylase.

The inhibition of α-glucosidase and α-amylase is a clinical strategy for the treatment of type II diabetes, and herbal medicines have been reported to credibly alleviate hyperglycemia. Our previous study has reported some constituents from plant or herbal sources targeted to α-glucosidase and α-amylase via molecular docking and enzymatic measurement, but the hypoglycemic potencies in cell system and mice have not been validated yet. This study was aimed to elucidate the hypoglycemic efficacy of docking selected compounds in cell assay and oral glucose and starch tolerance tests of mice. All test compounds showed the inhibition of α-glucosidase activity in Caco-2 cells. The decrease of blood sugar levels of test compounds in 30 min and 60 min of mice after OGTT and OSTT, respectively and the decreased glucose levels of test compounds were significantly varied in acarbose. Taken altogether, in vitro and in vivo experiments suggest that selected natural compounds (curcumin, antroquinonol, HCD, docosanol, tetracosanol, rutin, and actinodaphnine) via molecular docking were confirmed as potential candidates of α-glucosidase and α-amylase inhibitors for treating diabetes.

Neferine Potentiates the Antitumor Effect of Cisplatin in Human Lung Adenocarcinoma Cells Via a Mitochondria-Mediated Apoptosis Pathway.

Cisplatin is one of the most potent chemotherapeutic agents for the treatment of many types of solid tumors but its efficacy is often limited by the development of resistance and dose limiting toxicity. Neferine is an alkaloid isolated from seed embryo of Nelumbo nucifera, it has recently been shown to have anticancer effects in various human cancer cell lines. The present investigation is designed to study the chemosensitizing ability of neferine with cisplatin in A549 cells. Neferine potentiates the cisplatin induced apoptosis through the exploration of characteristic apoptotic morphological changes, induced sub-G1 cell cycle arrest, ROS hypergeneration, significant loss of cellular antioxidant enzymes, as well as loss of mitochondrial membrane potential (ΔΨM). Furthermore our results revealed that neferine combined with cisplatin down regulate the expression of Bcl-2 and up regulate the expression of Bax, Bad, Bak, release of cytochrome c, p53 levels, then activated cleavage forms of caspase-9, caspase-3, and PARP. Moreover neferine and cisplatin combination significantly down regulated the protein levels of FAK and VEGF. In addition, we observed the activity of MMP-2 and MMP-9. Thus this study provides molecular evidence for the ROS mediated apoptosis of the combinatorial regimen of cisplatin and neferine in lung cancer cells. Thus these results suggest that using neferine with cisplatin combinatorial regimen could be potentiating the effect of cisplatin and neferine reduces the cisplatin dose requirement in cancer chemotherapy. J. Cell. Biochem. 118: 2865-2876, 2017. © 2017 Wiley Periodicals, Inc.

Improving the regenerative potential of olfactory ensheathing cells by overexpressing prostacyclin synthetase and its application in spinal cord repair.

BACKGROUND: Olfactory ensheathing cells (OEC), specialized glia that ensheathe bundles of olfactory nerves, have been reported as a favorable substrate for axonal regeneration. Grafting OEC to injured spinal cord appears to facilitate axonal regeneration although the functional recovery is limited. In an attempt to improve the growth-promoting properties of OEC, we transduced prostacyclin synthase (PGIS) to OEC via adenoviral (Ad) gene transfer and examined the effect of OEC with enhanced prostacyclin synthesis in co-culture and in vivo. Prostacyclin is a vasodilator, platelet anti-aggregatory and cytoprotective agent. RESULTS: Cultured OEC expressed high level of cyclooxygneases, but not PGIS. Infection of AdPGIS to OEC could selectively augument prostacyclin synthesis. When cocultured with either OEC or AdPGIS-OEC, neuronal cells were resistant to OGD-induced damage. The resulted OEC were further transplanted to the transected cavity of thoracic spinal cord injured (SCI) rats. By 6 weeks post-surgery, significant functional recovery in hind limbs occurred in OEC or AdPGIS-OEC transplanted SCI rats compared with nontreated SCI rats. At 10-12 weeks postgraft, AdPGIS-OEC transplanted SCI rats showed significantly better motor restoration than OEC transplanted SCI rats. Futhermore, regenerating fiber tracts in the distal spinal cord stump were found in 40-60% of AdPGIS-OEC transplanted SCI rats. CONCLUSIONS: Enhanced synthesis of prostacyclin in grafted OEC improved fiber tract regeneration and functional restoration in spinal cord injured rats. These results suggest an important potential of prostacyclin in stimulating OEC therapeutic properties that are relevant for neural transplant therapies.

Inhibitory Growth of Oral Squamous Cell Carcinoma Cancer via Bacterial Prodigiosin.

Chemotherapy drugs for oral cancers always cause side effects and adverse effects. Currently natural sources and herbs are being searched for treated human oral squamous carcinoma cells (OSCC) in an effort to alleviate the causations of agents in oral cancers chemotherapy. This study investigates the effect of prodigiosin (PG), an alkaloid and natural red pigment as a secondary metabolite of Serratia marcescens, to inhibit human oral squamous carcinoma cell growth; thereby, developing a new drug for the treatment of oral cancer. In vitro cultured human OSCC models (OECM1 and SAS cell lines) were used to test the inhibitory growth of PG via cell cytotoxic effects (MTT assay), cell cycle analysis, and Western blotting. PG under various concentrations and time courses were shown to effectively cause cell death and cell-cycle arrest in OECM1 and SAS cells. Additionally, PG induced autophagic cell death in OECM1 and SAS cells by LC3-mediated P62/LC3-I/LC3-II pathway at the in vitro level. These findings elucidate the role of PG, which may target the autophagic cell death pathways as a potential agent in cancer therapeutics.

Excavatolide B inhibits nonsmall cell lung cancer proliferation by altering peroxisome proliferator activated receptor gamma expression and PTEN/AKT/NF-Kß expression.

Marine organisms are proven to be rich source of secondary metabolites that can be used to treat various diseases. Excavatolide B (Exc.B), the most abundant metabolite was found in the marine coral Briareum excavatum exhibits cytotoxic effects against lung cancer cell. Treatment of the A549 cells with Exc.B significantly reduced its cell viability and induced cell cycle arrest at subG1 phase in a dose- and time-dependent manner, respectively. Apoptosis induction by Exc.B was further confirmed by decreased pro-caspase 3 expressions and increased proteolytic cleavage of poly (ADP-ribose) polymerase (PARP) expression. Furthermore, Exc.B increased reactive oxygen species (ROS) and reactive nitrogen species (RNS) and also decreased the antioxidant enzymes such as, Catalase, GPx, SOD, GST, and GSH. The proteomic analysis data revealed that total thirty six proteins were altered by Exc.B. STRING database showed that most of the altered proteins have no interaction between each other. Based on these data, KSR1, RuVBL2, PPAR-γ, and Tenascin X proteins were chosen to validate the 2DE data by Western blotting. Additional experiments demonstrated that Exc.B induced PTEN expression and inhibited pAKT and NF-kB expression. These results provide a novel insight into mechanisms underlying the inhibition of A549 cells growth by excavatolide B. © 2016 Wiley Periodicals, Inc. Environ Toxicol 32: 290-301, 2017.