Combinatorial anticancer effects of curcumin and 5-fluorouracil loaded thiolated chitosan nanoparticles towards colon cancer treatment.

BACKGROUND: Evaluation of the combinatorial anticancer effects of curcumin/5-fluorouracil loaded thiolated chitosan nanoparticles (CRC-TCS-NPs/5-FU-TCS-NPs) on colon cancer cells and the analysis of pharmacokinetics and biodistribution of CRC-TCS-NPs/5-FU-TCS-NPs in a mouse model. METHODS: CRC-TCS-NPs/5-FU-TCS-NPs were developed by ionic cross-linking. The in vitro combinatorial anticancer effect of the nanomedicine was proven by different assays. Further the pharmacokinetics and biodistribution analyses were performed in Swiss Albino mouse using HPLC. RESULTS: The 5-FU-TCS-NPs (size: 150±40nm, zeta potential: +48.2±5mV) and CRC-TCS-NPs (size: 150±20nm, zeta potential: +35.7±3mV) were proven to be compatible with blood. The in vitro drug release studies at pH4.5 and 7.4 showed a sustained release profile over a period of 4 days, where both the systems exhibited a higher release in acidic pH. The in vitro combinatorial anticancer effects in colon cancer (HT29) cells using MTT, live/dead, mitochondrial membrane potential and cell cycle analysis measurements confirmed the enhanced anticancer effects (2.5 to 3 fold). The pharmacokinetic studies confirmed the improved plasma concentrations of 5-FU and CRC up to 72h, unlike bare CRC and 5-FU. CONCLUSIONS: To conclude, the combination of 5-FU-TCS-NPs and CRC-TCS-NPs showed enhanced anticancer effects on colon cancer cells in vitro and improved the bioavailability of the drugs in vivo. GENERAL SIGNIFICANCE: The enhanced anticancer effects of combinatorial nanomedicine are advantageous in terms of reduction in the dosage of 5-FU, thereby improving the chemotherapeutic efficacy and patient compliance of colorectal cancer cases.

Relevance of fiber integrated gelatin-nanohydroxyapatite composite scaffold for bone tissue regeneration.

Porous nanohydroxyapatite (nanoHA) is a promising bone substitute, but it is brittle, which limits its utility for load bearing applications. To address this issue, herein, biodegradable electrospun microfibrous sheets of poly(L-lactic acid)-(PLLA)-polyvinyl alcohol (PVA) were incorporated into a gelatin-nanoHA matrix which was investigated for its mechanical properties, the physical integration of the fibers with the matrix, cell infiltration, osteogenic differentiation and bone regeneration. The inclusion of sacrificial fibers like PVA along with PLLA and leaching resulted in improved cellular infiltration towards the center of the scaffold. Furthermore, the treatment of PLLA fibers with 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide enhanced their hydrophilicity, ensuring firm anchorage between the fibers and the gelatin-HA matrix. The incorporation of PLLA microfibers within the gelatin-nanoHA matrix reduced the brittleness of the scaffolds, the effect being proportional to the number of layers of fibrous sheets in the matrix. The proliferation and osteogenic differentiation of human adipose-derived mesenchymal stem cells was augmented on the fibrous scaffolds in comparison to those scaffolds devoid of fibers. Finally, the scaffold could promote cell infiltration, together with bone regeneration, upon implantation in a rabbit femoral cortical defect within 4 weeks. The bone regeneration potential was significantly higher when compared to commercially available HA (Surgiwear™). Thus, this biomimetic, porous, 3D composite scaffold could be offered as a promising candidate for bone regeneration in orthopedics.

2-(4-Fluoro-phen-yl)-1-(3-meth-oxy-phen-yl)-4,5-dimethyl-1H-imidazole.

In the title compound, C18H17FN2O, the imidazole ring makes dihedral angles of 68.81 (6) and 25.20 (8)° with the meth-oxy-phenyl and fluoro-phenyl rings, respectively. The dihedral angle between the meth-oxy-phenyl and fluoro-phenyl ring is 71.89 (6)°. In the crystal, mol-ecules are linked into inversion dimers with an R 2 (2)(8) graph-set motif by pairs of weak C-H⋯F inter-actions.

Insights into the compositional and temperature-mediated magnetic characteristics of chromium-doped ZnO nanoparticles.

This study explores the influence of chromium content and temperature on the magnetic characteristics of ZnO synthesized via the cost-effective coprecipitation approach. The host ZnO structure is not significantly changed by chromium doping, even at 5 wt.% of chromium concentration, according to x-ray diffraction studies. The Zn-O characteristic stretching vibration band at 480 cm-1and the other functional group attached to the Cr-doped ZnO nanoparticles are confirmed by Fourier-transform infrared (FTIR) spectroscopy studies. Diffuse reflectance spectroscopy analysis shows the interaction between chromium ions and ZnO causes bandgap narrowing, and the observed optical bandgap values fall as chromium content increases in the host ZnO matrix. Point defects such as zinc interstitial, zinc vacancy, and oxygen vacancy that exist in the Cr-doped ZnO nanoparticles are inveterate through photoluminescence spectroscopy. Vibrating sample magnetometry investigations reveal weak ferromagnetic behavior at low applied fields and diamagnetic signatures dominating at high applied fields in the Cr-doped ZnO nanoparticles at 300 K. The magnetic characteristics are also tunable in terms of temperatures, which opens new avenues for fabricating dilute magnetic semiconductors with various applications.

In vitro and in vivo evaluation of osteoporosis therapeutic peptide PTH 1-34 loaded pegylated chitosan nanoparticles.

Oral formulation of human parathyroid hormone 1-34 (PTH 1-34) is an alternative patient compliant route in treating osteoporosis. PTH 1-34 loaded chitosan nanoparticles were PEGylated (PEG-CS-PTH NPs) and characterized by DLS, SEM, TEM and FTIR. PEG-CS-PTH NP aggregates of 200-250 nm which in turn comprised 20 nm individual nanoparticles were observed in SEM and TEM images respectively. The PEG-CS-PTH NP with 40% encapsulation efficiency was subjected to an in vitro release in simulated rat body fluids. PEG-CS-PTH NP treated human primary osteoblast cells, upon PTH 1-34 receptor activation, produced second messenger-cAMP, which downstream stimulated intracellular calcium uptake, production of bone specific alkaline phosphatase, osteocalcin etc., which substantiates the anabolic effect of the peptide. PEG-CS-PTH NPs showed an oral bioavailability of 100-160 pg/mL PTH 1-34 throughout 48 h, which is remarkable compared to the bare PTH 1-34 and CS-PTH NPs. The NIR image of gastrointestinal transit of ICG conjugated PEG-CS-PTH NPs supports this significant finding.

2,4-Bis(furan-2-yl)-1,5-dimethyl-3-aza-bicyclo-[3.3.1]nonan-9-one.

In the title compound, C18H21NO3, the bicyclic ring system adopts a twin-chair conformation. The two methyl groups attached to the bicycle are in an equatorial orientation for both rings. One of the furan rings is disordered over two orientations with an occupancy ratio of 0.686 (6):0.314 (6). In the crystal, very long N-H⋯O hydrogen bonds connect the mol-ecules into a chain perpendicular to the ac plane.

1-(3-Meth-oxy-phen-yl)-4,5-dimethyl-2-phenyl-1H-imidazole.

In the title compound, C18H18N2O, the imidazole ring makes dihedral angles of 68.26 (7) and 22.45 (9)° with the meth-oxy-phenyl and phenyl rings, respectively. The dihedral angle between the meth-oxy-phenyl and phenyl ring is 71.86 (7)°. In the crystal, weak inter-molecular C-H⋯O and C-H⋯N hydrogen bonds link the mol-ecules into columns propagated in [101].

2,4-Bis(4-fluoro-phen-yl)-1,5-dimethyl-3-aza-bicyclo-[3.3.1]nonan-9-one.

The asymmetric unit of the title compound, C22H23F2NO, contains two independent mol-ecules, A and B. The bicyclic system adopts a twin-chair conformation in both mol-ecules. The dihedral angles between the fluoro-phenyl rings are 55.27 (8) and 56.37 (7)° in mol-ecules A and B, respectively. The NH groups are not involved in hydrogen bonding due to the steric hindrance of fluoro-phenyl groups. The crystal structure features weak C-H⋯O inter-actions.

Various surgical methods of impacted maxillary canine exposure: A case series.

Impacted tooth is often a common problem in dentistry. Maxillary canines are seen impacted most commonly in patients undergoing orthodontic treatment without reaching the line of occlusion. These impactions are commonly due to physical obstructions and the difference in the direction of movement of the tooth. Canines are the cornerstones for esthetic smile and functional occlusion. Hence, surgical exposure of these impacted canines, guiding them toward the line of occlusion, plays a very important role in the maintenance of the health of periodontium. A series of cases are discussed on various techniques that can be used in guiding the direction or altering the direction of impacted canines to bring them into a proper occlusion without disturbing the health of periodontium.

Propan-2-yl r-4-(4-fluoro-phen-yl)-3-hy-droxy-c-6-methyl-2-phenyl-4,5-dihydro-2H-indazole-t-5-carboxyl-ate.

In the title compound, C(24)H(23)FN(2)O(3), the cyclo-hexene ring adopts a screw-boat conformation. The fluorobenzene ring attached to the cyclo-hexene ring and the phenyl ring attached to the indazole moiety are inclined to one another by 57.77 (13)°. In the crystal, mol-ecules are linked by O-H⋯N and C-H⋯O hydrogen bonds, forming chains with C(5) and C(10) graph-set motifs. There are also C-H⋯π inter-actions present. The isopropoxycarbonyl group undergoes considerable thermal motion.

16α,17α-Ep-oxy-17ß-(1H-imidazol-1-yl)androst-4-en-3-one monohydrate.

In the title compound, C(22)H(28)N(2)O(2)·H(2)O, rings B and C adopt chair conformations. Ring A adopts an envelope conformation, with the non-fused C atom adjacent to the fused C atom bearing a methyl group as the flap atom. Ring D also adopts an envelope conformation, with the fused C atom not bearing a methyl group as the flap atom. The water mol-ecule links the mol-ecules via O-H⋯O and O-H⋯N hydrogen bonds, forming zigzag chains which run parallel to the c axis. Weak C-H⋯O inter-actions also occur.

c-5-Hy-droxy-r-2,c-4-bis-(meth-oxy-carbon-yl)-t-5-methyl-t-3-(3-nitro-phen-yl)cyclo-hexa-none.

In the title compound, C(17)H(19)NO(8) [systematic name = dimethyl 4-hydroxy-4-methyl-2-(3-nitrophenyl)-6-oxocyclohexane-1,3-dicarboxylate], the cyclo-hexa-none ring exhibits a chair conformation. The meth-oxy-carbonyl groups are oriented in opposite directions with respect to the cyclo-hexa-none ring. In the crystal, O-H⋯O hydrogen bonds links the mol-ecules into chains running parallel to the a axis. These chains are connected by weak C-H⋯O hydrogen bonds, forming sheets parallel to the ab plane.

Classification of Myopathy and Amyotrophic Lateral Sclerosis Electromyograms Using Bat Algorithm and Deep Neural Networks.

Electromyograms (EMG) are a recorded galvanic action of nerves and muscles which assists in diagnosing the disorders associated with muscles and nerves. The efficient discrimination of abnormal EMG signals, myopathy and amyotrophic lateral sclerosis, engage crucial role in automatic diagnostic assistance tools, since EMG signals are nonstationary signals. Hence, for computer-aided identification of abnormalities, extraction of features, selection of superlative feature subset, and developing an efficient classifier are indispensable. Initially, time domain and Wigner-Ville transformed time-frequency features were extracted from abnormal EMG signals for experiments. The selection of substantial characteristics from time and time-frequency features was performed using bat algorithm. Extensively, deep neural network classifier is modelled for selected feature subset using bat algorithm from extracted time and time-frequency features. The performance of deep neural network exerting selected features from bat algorithm was compared with conventional artificial neural network. Results demonstrate that the deep neural network modelled with layers 2 and 3 (neurons = 2 and 4) using time domain features is efficient in classifying the abnormalities of EMG signals with an accuracy, sensitivity, and specificity of 100% and also exhibited finer performance. Correspondingly, the developed conventional single layer artificial neural network (neurons = 7) with time domain features has shown an accuracy of 83.3%, sensitivity of 100%, and specificity of 71.42%. The work materializes the significance of conventional and deep neural network using time and time-frequency features in diagnosing the abnormal signals exists in neuromuscular system using efficient classification.

In vitro and in silico studies of silver nanoparticles (AgNPs) from Allium sativum against diabetes.

In the present study, the silver nanoparticles (AgNPs) were synthesized from the bulbs of Allium sativum, characterized by UV-visible spectroscopy, FT-IR, SEM, HR-TEM, EDAX analysis and investigated its action on the inhibition of starch digestion. The results proved that the biosynthesized nanoparticles were uniformly dispersed, spherical shaped with the size ranging from 10 to 30 nm. The phytochemical and FT-IR analysis showed the presence of phenols, terpenoids, and amino acids in the synthesized AgNPs. The cytotoxicity analysis revealed that the synthesized AgNPs were non-toxic to the normal cells. The synthesized AgNPs exhibited significant free radical scavenging activity. The in vitro antidiabetic activity showed that the synthesized AgNPs increased glucose utilization, decreased hepatic glucose production, inhibited the activity of starch digestive enzymes such as α-amylase and α-glucosidase, and were not involved in the stimulation of pancreatic cells for the secretion of insulin. The in silico antidiabetic activity analysis (molecular docking) also revealed that the silver atoms of the AgNPs interacted with the amino acid residues of α-amylase, α-glucosidase, and insulin. The present study proved that the AgNPs synthesized from A. sativum have prominent antidiabetic activity in terms of reducing the hyperglycemia through the increased glucose utilization, decreased hepatic glucose production, and the inhibition of α-amylase and α-glucosidase enzymes. So it can be used as a promising nanomedicine for the treatment of diabetes.

Bone Loss Evaluation by Cone Beam Computed Tomography Postdental Implant Placement: An Original Research.

Introduction: The success of the prosthetic rehabilitation is a factor of the periodontal reactions. Hence, in the current study, we aim to assess bone loss in the osseointegrated implants posttreatment by the cone beam computed tomography (CBCT) imaging. Materials and Methods: We conducted a prospective clinical observational study among 50 subjects who received mandibular dental implants for the replacement of the single lost anterior tooth. The follow-up was done at 1 week, 2 weeks, and after 6 weeks. The bone loss around the implant was noted by imaging with CBCT. The values were compared and analyzed statistically. Results: We observed a significant variation among the genders and the age groups. The mean bone loss around the implants was statistically significant for the different time intervals (P = 0.001). Conclusion: Significant bone loss was noted in the first few weeks after implantation. Care should be focused in the initial posttreatment phase to eliminate the factors aggravating the periodontitis.

EHMO-Based Deep ResNet for Survival Timeline Prediction of Adenocarcinoma Cancer.

Lung cancer is due to the growth of uncontrolled cells in the lungs, and the death rate is high compared with all types of cancer. It is recognized and treated using images of computed tomography (CT). This paper develops the elephant herding magnetic optimization-based deep residual network (EHMO-based Deep ResNet) for survival timeline prediction in adenocarcinoma. Here, preprocessing is performed using a Gaussian filter for the lung CT image. The preprocessed image is subjected to lung lobe segmentation, which is performed by the active contour model. Nodule identification locates nodules in the segmented image, where the process is carried out using a grid-based scheme. After that, feature extraction is carried out to extract intensity, wavelet, tetrolet transform, local optimal oriented pattern (LOOP), and clinical features. Finally, the extracted features are fed to the prediction module, which is based on the Deep ResNet classifier, which is trained by the proposed EHMO optimization algorithm. Here, the developed EHMO combines elephant herding optimization (EHO) and the magnetic optimization algorithm (MOA). The developed adenocarcinoma survival timeline prediction technique exhibits efficient performance in terms of accuracy, 0.955; maximal sensitivity, 0.962; and high specificity, 0.958.

Genetic analyses of roundabout (ROBO) axon guidance receptors in autism.

Autism is a pervasive developmental disorder diagnosed in early childhood. Abnormalities of serotonergic neurotransmission have been reported in autism. Serotonin transporter (SERT) modulates serotonin levels, and is a major therapeutic target in autism. Factors that regulate SERT expression might be implicated in the pathophysiology of autism. One candidate SERT regulatory protein is the roundabout axon guidance molecule, ROBO. SerT expression in Drosophila is regulated by robo; it plays a vital role in mammalian neurodevelopment also. Here, we examined the associations of ROBO3 and ROBO4 with autism, in a trio association study using DNA from 252 families recruited to AGRE. Four SNPs of ROBO3 (rs3923890, P = 0.023; rs7925879, P = 0.017; rs4606490, P = 0.033; and rs3802905, P = 0.049) and a single SNP of ROBO4 (rs6590109, P = 0.009) showed associations with autism; the A/A genotype of rs3923890 showed lower ADI-R_A scores, which reflect social interaction. Significant haplotype associations were also observed for ROBO3 and ROBO4. We further compared the mRNA expressions of ROBO1, ROBO2, ROBO3, and ROBO4 in the lymphocytes of 19 drug-naïve autistic patients and 20 age- and sex-matched controls. Expressions of ROBO1 (P = 0.018) and ROBO2 (P = 0.023) were significantly reduced in the autistic group; the possibility of using the altered expressions of ROBO as peripheral markers for autism, may be explored. In conclusion, we suggest a possible role of ROBO in the pathogenesis of autism. Abnormalities of ROBO may lead to autism either by interfering with serotonergic system, or by disrupting neurodevelopment. To the best of our knowledge, this is the first report relating ROBO with autism.

Poly(L-lactic acid) nanofibers containing Cissus quadrangularis induced osteogenic differentiation in vitro.

Cissus quadrangularis (CQ) is known as "bone setter" in Ayurvedic Medicine because of its ability to promote fracture healing. Polymers incorporated with CQ at lower concentration have shown to enhance osteogenic differentiation of mesenchymal stem cells (MSCs) in vitro. However, for the healing of clinically relevant critical sized bone defects, large amount of CQ would be required. Based on this perception, a herbal fibrous sheet containing high weight percentage of CQ [20,40 and 60wt/wt% in poly (L-lactic acid) (PLLA)] was fabricated through electrospinning. The solution concentration, flow rate, voltage and tip-target distance was optimized to obtain nanofibers. The hydrophobicity of PLLA fibers was reduced through CQ incorporation. There was considerable increase in the adhesion, proliferation and osteogenic differentiation of MSCs on herbal fibers than normal fibers, mainly on P-Q20 and P-CQ40. MSCs were differentiated into osteoblasts without providing any osteogenic supplements in the medium, indicating its osteoinductive capability. The herbal sheet also could promote mineralization when immersed in simulated body fluid for 14days. These studies specify that PLLA nanofibers loaded with 20 and 40wt% of CQ could serve as a potential candidate for bone tissue engineering applications.

Effectiveness of Peripheral Intravenous Skill Continuing Education Using Low-Fidelity Simulation Among Nurses in India.

BACKGROUND: Many nurses have limited opportunities to practice peripheral intravenous (IV) skill access until they begin their nursing career, particularly in limited resource settings. Continuing nursing education is needed for practicing nurses to build nurse capacity and skill accuracy in IV access globally. METHOD: A pretest-posttest design was used to measure effectiveness of peripheral IV continuing education among 180 nurses in India. A skills checklist was used to observe for skill accuracy using low-fidelity simulation. RESULTS: A statistically significant improvement in knowledge regarding peripheral IV skill access and care was found (p < .001), and 95% of nurse participants successfully simulated IV access accuracy after the continuing education intervention. CONCLUSION: Findings support the need for continuing nursing education to improve peripheral IV access and care knowledge and skill among nurses, particularly in low- and middle-income countries or other settings where hands-on experience is limited during undergraduate nursing education programs. J Contin Educ Nurs. 2018;49(6):255-261.