Chemopreventive Efficacy of Sulindac Sulfone as a Selective Apoptotic Antineoplastic Drug in Human Head and Neck Squamous Cell Carcinoma Cell Lines: A Systematic Review.

Sulindac sulfone, an active metabolite of sulindac, a non-steroidal anti-inflammatory drug, has good anti-inflammatory potential. The antineoplastic effect of sulindac sulfone is mediated through a cyclooxygenase inhibitory mechanism, followed by apoptosis and inhibition of cell proliferation. Mounting studies have explored the anti-neoplastic effect of sulindac sulfone in various types of cancers in a dose-dependent manner. In this backdrop, we have conducted a systematic review to evaluate the efficacy and dose of sulindac sulfone as an anti-neoplastic agent in human head and neck squamous cell carcinoma cell lines (HNSCCs). In this study, we used a systematic literature review approach, and articles were searched in PubMed, and Medline with the keywords "sulindac sulfone," "anti-neoplastic activity," "chemopreventive," and "head and neck squamous cell carcinoma". A hand-search of journals was also performed. Articles were reviewed and analyzed. The analysis reveals that, based on the in vitro studies on various tumor models, the optimum concentration of sulindac sulfone which elicits anti-neoplastic effects is 200-800 µM. The anti-neoplastic effect is mediated through inhibition of cell proliferation and apoptosis. The results of our systematic review show that the anti-neoplastic activity of pharmacologic Sulindac sulfone is part of its dose-dependent activity, which can be safely employed in the therapy for human HNSCCs and would be responsible for a beneficial outcome of the treatment.

Cemento-Ossifying Fibroid Epulis in the Posterior Maxilla.

Cemento-ossifying fibroma is a benign fibro-osseous lesion arising from the periodontal ligament and has the potential to form cementum and bone in the periodontal ligament. Cemento-ossifying fibroma is a painless, pedunculated, or sessile, smooth exophytic growth arising attached to the gingival tissues. We present a case of cemento-ossifying fibroid epulis in the posterior maxilla attached to the interdental gingiva between the 26 and 27 region buccally in a 52-year-old female patient managed with surgical excision of the lesion, extraction of the involved teeth, curettage, and palatal obturator while under general anesthesia. The patient was followed up post-operatively, healing was satisfactory, there were no signs of infection, and no recurrence was noted in the six-month follow-up period.

Do preoperative pancreatic computed tomography attenuation index and enhancement ratio predict pancreatic fistula after pancreaticoduodenectomy?

BACKGROUND: The commonly used predictors of clinically relevant postoperative pancreatic fistula (CR-POPF) following pancreaticoduodenectomy (PD) have subjective assessment components and can be used only in the postoperative setting. Also, the available objective predictors based on preoperative cross-sectional imaging were not prospectively studied. AIM: To evaluate the accuracy of the pancreatic attenuation index (PAI) and pancreatic enhancement ratio (PER) for predicting CR-POPF following PD and its correlation with pancreatic fat fraction and fibrosis. METHODS: A prospective observational study included patients who underwent PD for benign and malignant pathology of the periampullary region or pancreatic head between February 2019 and February 2021. Patients undergoing extended or total pancreatectomy and those with severe atrophy of pancreatic tissue or extensive parenchymal calcifications in the pancreatic head and neck precluding calculation of PAI and PER were excluded from the study. Preoperatively PAI was measured in the neck of the pancreas by marking regions of interest (ROI) in the non-contrast computed tomography (CT), and PER was measured during the contrast phase of the CT abdomen. Also, the fibrosis score and fat fraction of the pancreatic neck were assessed during the histopathological examination. Demographic, clinical and preoperative radiological indices (PAI, PER) were evaluated to predict CR-POPF. Preoperative pancreatic neck CT indices were correlated with the histopathological assessment of fat fraction and fibrosis. RESULTS: Of the 70 patients who underwent PD, 61 patients fulfilling the inclusion criteria were included in the analysis. The incidence of CR-POPF was 29.5% (18/61). PAI had no association with the development of CR-POPF. Of the preoperative parameters, PER (mean ± standard deviation [SD]) was significantly lower in patients developing CR-POPF (0.58 ± 0.20 vs 0.81 ± 0.44, P = 0.006). The area under the curve for the PER was 0.661 (95%CI: 0.517-0.804), which was significant (P = 0.049). PER cut-off of 0.673 predicts CR-POPF with 77.8% sensitivity and 55.8% specificity. PAI and PER had a weak negative correlation (Strength-0.26, P = 0.037). Also, PER showed a moderately positive correlation with fibrosis (Strength 0.50, P < 0.001). Patients with CR-POPF had a significantly higher incidence of the intraabdominal abscess (50% vs 2.3%, P < 0.001), delayed gastric emptying (83.3% vs 30.2, P < 0.001), and prolonged mean (± SD) postoperative hospital stay (26.8 ± 13.9 vs 9.6 ± 3.6, P = 0.001). CONCLUSION: PER exhibited good accuracy in predicting the development of CR-POPF. PER additionally showed a good correlation with PAI and fibrosis scores and may be used as an objective preoperative surrogate for assessing pancreatic texture. However, ROI-based PAI did not show any association with CR-POPF and pancreatic fat fraction.

Study on reversal of ABCB1 mediated multidrug resistance in Colon cancer by acetogenins: An in-silico approach.

Multi-Drug Resistance (MDR) exerted by tumor cells is majorly due to the overexpression of ATP Binding cassette transporters such as ABCB1/P-glycoprotein (P-gp). Annonaceous acetogenins (AGEs) exert anticancer activity by strongly inhibiting NADH oxidase of cancer cells. The present in silico study aims at screening a potent MDR inhibitor among acetogenins from the plant Annona muricata. Twenty-four AGEs were selected and screened for their pharmacokinetic properties. An inward facing conformation of P-gp is required for understanding the interaction of AGEs at the drug binding region and hence the human P-gp protein was modeled. The selected compounds were then docked with the ATP binding site and the drug binding site of modeled human P-gp. Annonacin A.1, Annohexocin.1 and Annomuricin E.1 docked better with high MM/GBSA dG binding in the drug binding region as compared with the conventional drugs. These compounds had a better docking score as compared with control inhibitor drugs at the ATP binding region. The complexes were subjected to MD simulation and Annonacin A was stable throughout the simulation period. Therefore, Annonacin A might act as a competitive inhibitor for the chemo drugs for binding at the drug binding region of P-gp. Hence it is capable of decreasing the efflux of chemo drugs out of the cells by P-Glycoprotein/ABCB1/MDR1. With this computational study, it is concluded that this compound might potentially reverse MDR, and hence can be taken forward for validation studies.Communicated by Ramaswamy H. Sarma.

Predictors of Functional Outcome in Unstable Ankle Fractures Treated Surgically - A Prospective Cohort Study.

INTRODUCTION: Unstable ankle injuries require anatomical reduction and stabilisation for optimal outcome. In spite of adequate care, a few patients have poor outcome. In this study, we assessed the risk factors that predict the clinical outcomes in surgically treated unstable ankle fractures. MATERIAL AND METHODS: This prospective cohort study was conducted on 68 patients who underwent surgical management for an unstable ankle injury. Demographic details, fracture type and associated medical comorbidities were recorded. Pre-operative radiographic assessment was done for all patients. At the end of one year follow-up, clinical (American Orthopaedic foot and ankle society-AOFAS and Olerud-Molander ankle - OMAS) scores and radiological parameters were assessed and analysed. RESULTS: Fracture dislocation (0.008), diabetes mellitus (0.017), level of alchohol consumption (0.008) and pre-operative talocrural angle (TCA) > 100° (0.03) were significant predictors of poor outcomes as per AOFAS. Fracture dislocation (0.029), diabetes mellitus (0.004), pre-operative TCA > 100° (0.009), female gender (0.001), age more than 60 years (0.002) and open injuries (0.034) had significantly poor outcome as per OMAS. Other parameters (smoking, hypertension, classification, syndesmotic injury, medial clear space and tibiofibular overlap) did not affect the outcome significantly. CONCLUSION: Our study showed that poor outcome predictors in unstable ankle fractures are age >60 years, female gender, diabetes mellitus, alcohol consumption, fracture dislocation, open fractures and pre-op TCA >100°.

Stabilization and X-ray Attenuation of PEGylated Cholesterol/Polycaprolactone-Based Perfluorooctyl Bromide Nanocapsules for CT Imaging.

Contrast-enhanced X-ray computed tomography plays an important role in cancer imaging and disease progression monitoring. Imaging using radiopaque nanoparticle platforms can provide insights on the likelihood of nanoparticle accumulation and can enable image-guided therapies. Perfluorooctyl bromide (PFOB)-loaded nanocapsules designed for this purpose were stabilized using an in-house synthesized PEGylated polycaprolactone-based copolymer (PEG-b-PCL(Ch)) and compared with commercial polycaprolactone employing a Quality-by-Design approach. PFOB is a dense liquid, weakly polarizable, and immiscible in organic and aqueous solvents; thus, carefully designed formulations for optimal colloidal stabilization to overcome settling-associated instability are required. PFOB-loaded nanocapsules exhibited high PFOB loading due to the intrinsic properties of PEG-b-PCL(Ch). Settling and caking are major sources of instability for PFOB formulations. However, the PEG-b-PCL(Ch) copolymer conferred the nanocapsules enough steric impediment and polymer shell elasticity to settle without significant caking, increasing the overall colloidal stability of the formulation. Furthermore, a clear relationship between nanocapsule physical properties and X-ray attenuation was established. Nanocapsules were able to enhance the X-ray contrast in vitro as a function of PFOB loading. This nanocapsule-based platform is promising for future translational studies and image-guided tumor therapy due to its enhanced contrastability and optimal colloidal stability.

Quantification of biomaterial dispersion during otologic procedures and role of barrier drapes in Covid 2019 era - a laboratory model.

BACKGROUND: Aerosol generation during temporal bone surgery caries the risk of viral transmission. Steps to mitigate this problem are of particular importance during the coronavirus disease 2019 pandemic. OBJECTIVE: To quantify the effect of barrier draping on particulate material dispersion during temporal bone surgery. METHODS: The study involved a cadaveric model in a simulated operating theatre environment. Particle density and particle count for particles sized 1-10 µ were measured in a simulated operating theatre environment while drilling on a cadaveric temporal bone. The effect of barrier draping to decrease dispersion was recorded and analysed. RESULTS: Barrier draping decreased counts of particles smaller than 5 µ by a factor of 80 in the operating theatre environment. Both particle density and particle count showed a statistically significant reduction with barrier draping (p = 0.027). CONCLUSION: Simple barrier drapes were effective in decreasing particle density and particle count in the operating theatre model and can prevent infection in operating theatre personnel.

Overcoming Wnt-ß-catenin dependent anticancer therapy resistance in leukaemia stem cells.

Leukaemia stem cells (LSCs) underlie cancer therapy resistance but targeting these cells remains difficult. The Wnt-ß-catenin and PI3K-Akt pathways cooperate to promote tumorigenesis and resistance to therapy. In a mouse model in which both pathways are activated in stem and progenitor cells, LSCs expanded under chemotherapy-induced stress. Since Akt can activate ß-catenin, inhibiting this interaction might target therapy-resistant LSCs. High-throughput screening identified doxorubicin (DXR) as an inhibitor of the Akt-ß-catenin interaction at low doses. Here we repurposed DXR as a targeted inhibitor rather than a broadly cytotoxic chemotherapy. Targeted DXR reduced Akt-activated ß-catenin levels in chemoresistant LSCs and reduced LSC tumorigenic activity. Mechanistically, ß-catenin binds multiple immune-checkpoint gene loci, and targeted DXR treatment inhibited expression of multiple immune checkpoints specifically in LSCs, including PD-L1, TIM3 and CD24. Overall, LSCs exhibit distinct properties of immune resistance that are reduced by inhibiting Akt-activated ß-catenin. These findings suggest a strategy for overcoming cancer therapy resistance and immune escape.

Influence of the method of preparation on the characteristics and performance of cholesterol-based polymeric nanoparticles for redox-triggered release of doxorubicin in tumor cells.

Immature manufacturing and sub-optimal control of quality attributes hinder the effective translation of nanoformulations for cancer treatment, being partially responsible for the scarce number of products on the market. The effect of the method of preparation on the performance of complex formulations such as bio-responsive nanomedicines needs further understanding. In this study, we investigated the the influence of the method of preparation on the characteristics and bio-responsiveness of doxorubicin-loaded redox-sensitive nanoparticles (DOX-SS-NPs), formed by a biocompatible cholesterol-based amphiphilic block copolymer (PC5MA-SS-PEO). Two commonly used preparation techniques: (1) cosolvent removal and (2) an O/W emulsion method were compared and the in vitro and in vivo performance of promising formulations was assessed. Besides particle size distribution and drug loading, the response of the nanoparticles to reducing environments and subsequent release kinetics and cytotoxicity were also affected by the method of preparation. The investigation and understanding of this extensive influence, led to a DOX-SS-NPs formulation with significant in vivo efficacy and an improved safety profile when evaluated against free doxorubicin (DOX-HCl) and the commercial pegylated liposomal form (Doxil®). Our findings highlight the importance of formulation optimization and support the use of systematic approaches like Quality by Design to the development of bio-responsive nanomedicines for cancer treatment.

Kinetic and equilibrium modeling of biosorption of nickel (II) and cadmium (II) on brewery sludge.

In the current study, utilization of industrial waste brewery sludge for the biosorption of nickel (II) and cadmium (II) has been explored. The suitable conditions for the effective removal of Ni (II) and Cd (II) from aqueous solutions were examined. The kinetic evaluation showed that the biosorption process using the sludge followed pseudo-second order kinetics. In the presence of a metal co-ion, competitive and preferential biosorption was observed. The Langmuir model and Freundlich model were able to describe the sorption equilibrium for biosorption of Ni (II) and Cd (II) ions in single and dual metal systems. The effects of co-ion concentrations onto mono-component isotherm parameters (Langmuir and Freundlich) were studied and the inhibitory effect of co-ion concentration was observed. The effective reusability of biomass was assessed by three cycles of sorption-desorption. The sludge, owing to its high biosorption intensity and large availability from the local supply, is a better biosorbent for the treatment of Ni (II) and Cd (II) contaminated water.

Reduced in vivo toxicity of doxorubicin by encapsulation in cholesterol-containing self-assembled nanoparticles.

We previously reported the development of an amphiphilic brush-like block copolymer composed of polynorbornene-cholesterol/polyethylene glycol (P(NBCh9-b-NBPEG)) that self-assembles in aqueous media to form long circulating nanostructures capable of encapsulating doxorubicin (DOX-NPs). Biodistribution studies showed that this formulation preferentially accumulates in tumor tissue with markedly reduced accumulation in the heart and other major organs. The aim of the current study was to evaluate the in vivo efficacy and toxicity of DOX containing self-assembled polymer nanoparticles in a mouse xenograft tumor model and compare its effects with the hydrochloride non-encapsulated form (free DOX). DOX-NPs significantly reduced the growth of tumors without inducing any apparent toxicity. Conversely, mice treated with free DOX exhibited significant weight loss, early toxic cardiomyopathy, acute toxic hepatopathy, reduced hematopoiesis and fatal toxicity. The improved safety profile of the polymeric DOX-NPs can be explained by the low circulating concentration of non-nanoparticle-associated drug as well as the reduced accumulation of DOX in non-target organs. These findings support the use of P(NBCh9-b-NBPEG) nanoparticles as delivery platforms for hydrophobic anticancer drugs intended to reduce the toxicity of conventional treatments.

Redox-sensitive nanoparticles from amphiphilic cholesterol-based block copolymers for enhanced tumor intracellular release of doxorubicin.

A novel amphiphilic cholesterol-based block copolymer comprised of a polymethacrylate bearing cholesterol block and a polyethylene glycol block with reducible disulfide bonds (PC5MA-SS-PEO) was synthesized and evaluated as a redox-sensitive nanoparticulate delivery system. The self-assembled PC5MA-SS-PEO nanoparticles (SS-NPs) encapsulated the anticancer drug doxorubicin (DOX) with high drug loading (18.2% w/w) and high encapsulation efficiency (94.9%). DOX-encapsulated PC5MA-SS-PEO self-assembled nanoparticles (DOX-encapsulated SS-NPs) showed excellent stability and exhibited a rapid DOX release in response to dithiothreitol reductive condition. Importantly, following internalization by lung cancer cells, the reducible DOX-encapsulated SS-NPs achieved higher cytotoxicity than the non-reducible thioester NPs whereas blank nanoparticles were non-cytotoxic. Furthermore, in vivo imaging studies in tumor-bearing severe combined immunodeficiency (SCID) mice showed that the nanoparticles preferentially accumulated in tumor tissue with remarkably reduced accumulation in the healthy non-target organs. The results indicated that the SS-NPs may be a promising platform for cancer-cell specific delivery of hydrophobic anticancer drugs. FROM THE CLINICAL EDITOR: The use of nanocarriers for drug delivery against tumors has been under intense research. One problem of using carrier system is the drug release kinetics at tumor site. In this article, the authors continued their previous study in the development of an amphiphilic cholesterol-based block copolymer with redox-sensitive modification, so that the payload drug could be released in response to the microenvironment. The interesting results should provide a new direction for designing future novel nanocarrier systems.

Long circulating self-assembled nanoparticles from cholesterol-containing brush-like block copolymers for improved drug delivery to tumors.

Amphiphilic brush-like block copolymers composed of polynorbonene-cholesterol/poly(ethylene glycol) (P(NBCh9-b-NBPEG)) self-assembled to form a long circulating nanostructure capable of encapsulating the anticancer drug doxorubicin (DOX) with high drug loading (22.1% w/w). The release of DOX from the DOX-loaded P(NBCh9-b-NBPEG) nanoparticles (DOX-NPs) was steady at less than 2% per day in PBS. DOX-NPs were effectively internalized by human cervical cancer cells (HeLa) and showed dose-dependent cytotoxicity, whereas blank nanoparticles were noncytotoxic. The DOX-NPs demonstrated a superior in vivo circulation time relative to that of free DOX. Tissue distribution and in vivo imaging studies showed that DOX-NPs preferentially accumulated in tumor tissue with markedly reduced accumulation in the heart and other vital organs. The DOX-NPs greatly improved survival and significantly inhibited tumor growth in tumor-bearing SCID mice compared to that for the untreated and free DOX-treated groups. The results indicated that self-assembled P(NBCh9-b-NBPEG) may be a useful carrier for improving tumor delivery of hydrophobic anticancer drugs.

A structural insight into major groove directed binding of nitrosourea derivative nimustine with DNA: a spectroscopic study.

Nitrosourea therapeutics occupies a definite place in cancer therapy but its exact mechanism of action has yet to be established. Nimustine, a chloroethyl nitrosourea derivative, is used to treat various types of malignancy including gliomas. The present work focuses on the understanding of nimustine interaction with DNA to delineate its mechanism at molecular level. Attenuated total reflection-Fourier transform infrared (ATR-FTIR) has been used to determine the binding sites of nimustine on DNA. Circular dichroism (CD) spectroscopy has been used to confirm conformational variations in DNA molecule upon nimustine-DNA interaction. Thermodynamic parameters of nimustine-DNA reaction have been calculated by isothermal titration calorimetry. Results of the present study demonstrate that nimustine is not a simple alkylating agent rather it causes major grove-directed-alkylation. Spectroscopic data suggest binding of nimustine with nitrogenous bases guanine (C6 = O6) and thymine (C4 = O4) in DNA major groove. CD spectra of nimustine-DNA complexes point toward the perturbation of native B-conformation of DNA and its partial transition into C-form. Thermodynamically, nimustine-DNA interaction is an entropy driven endothermic reaction, which suggests hydrophobic interaction of nimustine in DNA-major groove pocket. Spectral results suggest base binding and local conformational changes in DNA upon nimustine interaction. Investigation of drug-DNA interaction is an essential part of rational drug designing that also provides information about the drug's action at molecular level. Results, demonstrated here, may contribute in the development of new nitrosourea therapeutics with better efficacy and fewer side effects.

Chemical composition and larvicidal activity of essential oil from Mentha spicata (Linn.) against three mosquito species.

Mosquitoes are blood-feeding insects and serve as the most important vectors for spreading human diseases such as malaria, yellow fever, dengue fever, and filariasis. The continued use of synthetic insecticides has resulted in resistance in mosquitoes. Synthetic insecticides are toxic and affect the environment by contaminating soil, water, and air, and then natural products may be an alternative to synthetic insecticides because they are effective, biodegradable, eco-friendly, and safe to environment. Botanical origin may serve as suitable alternative biocontrol techniques in the future. Mentha spicata, an edible and medicinal plant, is chiefly distributed in Southeast Asia and South Asia. In the present study, the toxicity of mosquito larvicidal activity of leaf essential oil (EO) and their major chemical constituents from Mentha spicata against Culex quinquefasciatus, Aedes aegypti, and Anopheles stephensi. The chemical composition of the leaf EO was analyzed using gas chromatography-mass spectroscopy (GC-MS). GC-MS revealed that the EO of M. spicata contained 18 compounds. The major chemical components identified were carvone (48.60%), cis-carveol (21.30%), and limonene (11.30%). The EO had a significant toxic effect against early third-stage larvae of C. quinquefasciatus, A. aegypti, and A. stephensi with LC(50) values of 62.62, 56.08, and 49.71 ppm and LC(90) values of 118.70, 110.28, and 100.99 ppm, respectively. The three major pure constituents extracted from the M. spicata leaf EO were also tested individually against three mosquito larvae. The LC(50) values of carvone, cis-carveol, and limonene appeared to be most effective against A. stephensi (LC(50) 19.33, 28.50, and 8.83 ppm) followed by A. aegypti (LC(50) 23.69, 32.88, and 12.01 ppm), and C. quinquefasciatus (LC(50) 25.47, 35.20, and 14.07 ppm). The results could be useful in search for newer, safer, and more effective natural larvicidal agents against C. quinquefasciatus, A. aegypti, and A. stephensi.

DNA triplex-mediated inhibition of MET leads to cell death and tumor regression in hepatoma.

Mesenchymal epithelial transition factor (MET) is one of the critical cell signaling molecules whose aberrant expression is reported in several human cancers. The aim of the study is to investigate the antigene and antiproliferative effect of short triplex forming oligonucleotides, TFO-1 (part of the positive regulatory element) and TFO-2 (away from the transcription start site) on MET expression. HepG2 cells transfected only with TFO-1 (but not with TFO-2 and non-specific TFO) significantly decreased MET levels, which is accompanied by decrease in antiapoptotic proteins and increase in pro-apoptotic proteins. Phosphoproteome-array analysis of 46 intracellular kinases revealed hypophosphorylation of about 15 kinases including ERK, AKT, Src and MEK, suggesting the growth inhibitory effect of TFO-1. Further, the efficacy of TFO-1 was tested on diethylnitrosamine-induced liver tumors in wistar rats. T2-weighted magnetic resonance imaging showed decrease in liver tumor volume up to 90% after treatment with TFO-1. Decreased MET expression and elevated apoptotic activity further indicate that TFO-1 targeted to c-met leads to cell death and tumor regression in hepatoma. Formation of stable DNA triplex between TFO-1 and targeted gene sequence was confirmed by circular dichroic spectroscopy and gel retardation assay. Therefore, it can be concluded that DNA triplex-based therapeutic approaches hold promise in the treatment of malignancies associated with MET overexpression.

Side-chain liquid crystalline polymer networks: exploiting nanoscale smectic polymorphism to design shape-memory polymers.

Herein, we investigate the influence of nanoscale smectic polymorphism within end-on fixed side-chain liquid crystalline polymer networks (SCLCNs) on macroscopic shape-memory and actuation properties. We have synthesized a series of SCLC-type linear (TP-n) and cross-linked random terpolymers (XL-TP-n) with varying length of flexible methylene spacers (n = 5, 10, and 15) between polynorbornene main-chain and cholesteryl ester side-chains. Thermal and mechanical analyses by differential scanning calorimetry (DSC) and dynamic mechanical analysis (DMA) confirm a glass transition (T(g)), a clearing temperature (T(cl)), and a network structure in the XL-TP-n. Detailed structural investigation conducted using wide-angle and small-angle X-ray scattering (WAXS and SAXS) at room temperature proves self-assembled smectic A (SmA) polymorphism of the XL-TP-n which evolves from non-interdigitated bilayer (SmA(2)) for n = 5 to mixed layers of monolayer-like highly interdigitated layer (SmA(1)) and SmA(2) for n = 10 and to SmA(1) for n = 15. In addition, TP10 at temperatures above 60 °C interestingly shows transformation of SmA structure from mixed layer (SmA(1) + SmA(2)) to interdigitated structure (SmA(d)). The SmA polymorphism developed in TP-n during shape-memory cycles (SMCs) significantly impacts the ultimate strain responses. A mechanism for the unique interdigitation-based thermostrictive behavior is proposed. More importantly, this new actuation mechanism observed in these XL-TP-n can be exploited to develop intelligent thermal actuators.

Enamel formation in vitro in mouse molar explants exposed to amelogenin polypeptides ATMP and LRAP on enamel development.

OBJECTIVE: The enamel matrix contains amelogenin, leucine-rich amelogenin-polypeptide (LRAP), resulting from alternative splicing of the primary amelogenin-RNA transcript and tyrosine-rich amelogenin-polypeptide (TRAP), a proteolytic product of amelogenin. Presence of amelogenin-trityrosyl-motif peptide (ATMP) distinguishes TRAP from LRAP. The roles of these polypeptides in the formation of enamel remain to be elucidated. METHODS: The mouse in vitro molar tooth-organ developed from bud stage (E16) was exposed to LRAP, ATMP, and mutated ATMP (T-ATMP, third proline replaced by threonine). The histology and morphometry of the explants on day-12 in culture was examined using Mallory's stain. Guanidine-HCl soluble protein concentrations of explants were compared. RESULTS: The enamel width and protein solubility indicate that the explant on day-12 is comparable to postnatal molar on day-3 in vivo. The enamel of both untreated explants as well as that in vivo is fuchinophilic (acid fuchsin, AF+). ATMP reduced the ameloblast-height, accumulated AF+ spherules at the apical end of ameloblasts, and disrupted enamel-dentin bonding. T-ATMP abrogated deposition of AF+ material on the aniline blue positive (AB+) enamel matrix. LRAP reduced ameloblast-height, increased the enamel-width without disruption (at 17.25 nmol) and increased the density of AF+ dentinal tubules. AF+ substance from the tubules is released onto the surface of the dentin. The Guanidine-HCl-soluble protein is elevated in ATMP-treated explants but decreased in LRAP-treated explants. CONCLUSION: Exogenous ATMP, T-ATMP and LRAP have divergent effects on developing enamel. Exogenous ATMP, but not LRAP, abrogates enamel-dentin bonding at 17.25 nmol. LRAP may play a role in the differentiation of ameloblasts, growth of enamel and formation of dentinal tubules.

Circulating (cell-free) nucleic acids--a promising, non-invasive tool for early detection of several human diseases.

Circulating nucleic acids (CNA) are present in small amounts in the plasma of healthy individuals. However, increased levels of plasma CNA have been reported in a number of clinical disorders like cancer, stroke, trauma, myocardial infarction, autoimmune disorders, and pregnancy-associated complications. CNA has received special attention because of its potential application as a non-invasive, rapid and sensitive tool for molecular diagnosis and monitoring of acute pathologies and the prenatal diagnosis of fetal genetic diseases. This review throws light on the current status of blood CNA as a diagnostic marker and its potential as a powerful tool in the future.

Elevated levels of high-mobility-group chromosomal proteins, HMGA1, in murine skin carcinoma.

The high-mobility-group, HMGA1 (formerly HMGI(Y)) chromosomal proteins are known to be involved in gene regulation and their high expression is associated with neoplastic transformation of cells and metastatic tumor progression. Here, we present our results on the expression of HMGA1 in murine skin carcinoma as detected by acid-urea electrophoresis, reverse-phase high-performance liquid chromatography and Western blot. The enhanced expression of HMGA1 proteins directly correlates with the extent of cellular atypia and neoplastic changes noticed in the histopathology of tumor and suggest a potential use of these proteins as marker for determining the grade of skin tumor.