Anti-proliferative, -migratory and -clonogenic effects of long-lasting nitric oxide release in HepG2 cells.

Nitric oxide (NO) holds promise as a cytotoxic agent against tumors, but its gaseous nature and short half-life hinder direct administration to tumor tissues. Herein, we present novel 6,9-disubstituted purine derivatives designed to ensure sustained NO release, followed by study of their significant anti-proliferative, anti-migratory, and anti-clonogenic effects on HepG2 cell lines, highlighting NO release as a potent effector for treating hepatocellular carcinoma.

Photocytotoxic kinetically stable ruthenium(II)-N,N-donor polypyridyl complexes of oxalate with anticancer activity against HepG2 liver cancer cells.

Liver cancer is one of the leading causes of death that motivating scientists worldwide to synthesize novel chemotherapeutics. Ru(II)-polypyridyl complexes are extensively studied for possible therapeutic and cellular applications due to their tunable coordination chemistry, structural diversity, ligand-exchange kinetics, accessible redox states, and rich photophysical or photochemical properties. Herein, we have synthesized a series of Ru(II) polypyridyl complexes [RuII(N^N)2(ox)] (1-3), where ox is oxalate (C2O42-) and N^N is 1,10-phenanthroline (phen) (1), dipyrido[3,2-d:2',3'-f]quinoxaline (dpq) (2), and dipyrido[3,2,-a:2',3'-c]phenazine (dppz) (3). Oxalate (ox2-) was opted as a bioactive dioxo ligand to prevent facile hydrolysis in aqueous media, thereby increasing the stability of the Ru(II)-polypyridyl complexes in physiological media. We thoroughly characterized all the complexes using ESI-MS, FT-IR, UV-vis, and 1H NMR spectroscopy and other physicochemical methods. The complexes were stable under physiological conditions and under low-energy green LED light (λirr = 530 nm). However, the photoirradiation of complexes resulted in the efficient generation of singlet oxygen (1O2) as a major reactive oxygen species (ROS). The role of the extended aromatic conjugation of the N^N-donor ligands in the complexes was demonstrated by their binding propensities with CT-DNA and bovine serum albumin (BSA). Both DNA intercalation and groove binding were evidenced, while tryptophan (Trp) and tyrosine (Tyr) binding site preferences were revealed from the synchronous fluorescence spectra (SFS) of BSA. The cytotoxic profiling of the complexes performed on hepatocellular carcinoma cells (HepG2) in the dark and in the presence of green light indicated their dose-dependent cytotoxicity. The [RuII(N^N)2(ox)] complexes exhibited enhanced photocytotoxicity mediated by efficient generation of cytotoxic 1O2 and effective interaction with DNA. All the complexes were internalized by the HepG2 liver cancer cells efficiently and localized to the cytoplasm and nucleus. The complexes exhibited potent anti-proliferative, anti-clonogenic, and anti-migratory effects on the cancer cells, suggesting their potential for therapeutic applications.

Organic-inorganic composite of polypropylene fumarate and nanohydroxyapatite as carrier of antibiotics for the treatment of bone infections.

Current treatment approaches in clinics to treat the infectious lesions have partial success thus demanding the need for development of advanced treatment modalities. In this study we fabricated an organic-inorganic composite of polypropylene fumarate (PPF) and nanohydroxyapatite (nHAP) by photo-crosslinking as a carrier of two clinically used antibiotics, ciprofloxacin (CIP) and rifampicin (RFP) for the treatment of bone infections. Carboxy terminal-PPF was first synthesized by cis-trans isomerization of maleic anhydride which was then photo-crosslinked using diethylfumarate (DEF) as crosslinker and bis-acylphosphine oxide (BAPO) as photo-initiator under UV lights (P). A composite of PPF and nHAP was fabricated by incorporating 40 % of nHAP in the polymeric matrix of PPF (PH) which was then characterized for different physicochemical parameters. CIP was added along with nHAP to fabricated CIPloaded composite scaffolds (PHC) which was then coated with RFP to synthesize RFP coated CIP-loaded scaffolds (PHCR). It was observed that there was a temporal separation in the in vitro release of two antibiotics after coating PHC with RFP with 80.48 ± 0.40 % release of CIP from PHC and 62.43 ± 0.21 % release of CIP from PHCR for a period of 60 days. Moreover, in vitro protein adsorption was also found to be maximum in PHCR (154.95 ± 0.07 µg/mL) as observed in PHC (75.42 ± 0.06 µg/mL), PH (24.47 ± 0.08 µg/mL) and P alone (4.47 ± 0.02 µg/mL). The scaffolds were also evaluated using in vivo infection model to assess their capacity in reducing the bacterial burden at the infection site. The outcome of this study suggests that RFP coated CIP-loaded PPF composite scaffolds could reduce bacterial burden and simultaneously augment bone healing during infection related fractures.

Adversarial Data Augmentation and Transfer Net for Scrap Metal Identification Using Laser-Induced Breakdown Spectroscopy Measurement of Standard Reference Materials.

In this study, we propose a transfer learning-based classification model for identifying scrap metal using an augmented training dataset consisting of laser-induced breakdown spectroscopy (LIBS) measurement of standard reference material (SRMs) samples, considering varying experimental setups and environmental conditions. LIBS provides unique spectra for identifying unknown samples without complicated sample preparation. Thus, LIBS systems combined with machine learning methods have been actively studied for industrial applications such as scrap metal recycling. However, in machine learning models, a training set of the used samples may not cover the diversity of the scrap metal encountered in field measurements. Moreover, differences in experimental configuration, where laboratory standards and real samples are analyzed in situ, may lead to a wider gap in the distribution of training and test sets, dramatically reducing the performance of the LIBS-based fast classification system for real samples. To address these challenges, we propose a two-step Aug2Tran model. First, we augment the SRM dataset by synthesizing spectra of unobserved types through attenuation of dominant peaks corresponding to sample composition and generating spectra depending on the target sample using a generative adversarial network. Second, we used the augmented SRM dataset to build a robust real-time classification model with a convolutional neural network, which is further customized for the target scrap metal with limited measurements through transfer learning. For evaluation, SRMs of five representative metal types, including aluminum, copper, iron, stainless steel, and brass, are measured with a typical setup to form the SRM dataset. For testing, scrap metal from actual industrial fields is experimented with three different configurations, resulting in eight different test datasets. The experimental results show that the proposed scheme produces an average classification accuracy of 98.25% for the three experimental conditions, as high as the results of the conventional scheme with three separately trained and executed models. Additionally, the proposed model improves the classification accuracy of arbitrarily shaped static or moving samples with various surface contaminations and compositions, and even for differing ranges of charted intensities and wavelengths. Therefore, the proposed Aug2Tran model can be used as a systematic model for scrap metal classification with generalizability and ease of implementation.

Anti-infective composite cryogel scaffold treats osteomyelitis and augments bone healing in rat femoral condyle.

Bone and joint infections pose a serious challenge in the orthopedic medical condition which presents a major health care problem and economic burden to the patients. The current treatment strategies adopted have a very limited successful outcome in majority of the cases and need serious reconsiderations in terms of management, diagnosis and effective treatment approach. Herein, we have developed a composite cryogel scaffold from nanohydroxyapatite and collagen mimicking natural bone composition for the local delivery of antibiotic to treat osteomyelitis. The biomimetic and biodegradable antibiotic-loaded composite scaffold was found to be biocompatible with potent osteogenic capacity and anti-infective characteristics under in vitro conditions. Moreover, the anti-infective potency of the antibiotic-loaded composite cryogel was also evaluated in rat osteomyelitis model to cure the infection and promote bone healing. It was observed that anti-infective collagen-nanohydroxyapatite composite cryogel when loaded with bone morphogenetic protein-2 (BMP-2) and zoledronic acid (ZA) could completely eradicate the infection in rat femoral condyle and simultaneously, accelerate bone healing at the dead space created during surgical procedures. The approach developed in this study is the development of biomimetic and bioactive composite carrier of antibiotics for the treatment of bone infection. The findings of this study insinuate that this antibiotic-loaded composite cryogel scaffold could potentially be used as an anti-infective biomaterial for the treatment of bone infections which will simultaneosuly promote bone healing at the dead space created during surgical procedures.

Spinal cord regeneration: A brief overview of the present scenario and a sneak peek into the future.

The central nervous system (CNS) portrays appreciable complexity in developing from a neural tube to controlling major functions of the body and orchestrated co-ordination in maintaining its homeostasis. Any insult or pathology to such an organized tissue leads to a plethora of events ranging from local hypoxia, ischemia, oxidative stress to reactive gliosis and scarring. Despite unravelling the pathophysiology of spinal cord injury (SCI) and linked cellular and molecular mechanism, the over exhaustive inflammatory response at the site of injury, limited intrinsic regeneration capability of CNS, and the dual role of glial scar halts the expected accomplishment. The review discusses major current treatment approaches for traumatic SCI, addressing their limitation and scope for further development in the field under three main categories- neuroprotection, neuro-regeneration, and neuroplasticity. We further propose that a multi-disciplinary combinatorial treatment approach exploring any two or all three heads simultaneously might alleviate the inhibitory milieu and ameliorate functional recovery.

Cardiovascular Complications and its Impact on outcomes in COVID-19: An Original Research.

INTRODUCTION: The viral infection COVID-19 is highly infectious and has claimed many lives till date and is still continuing to consume lives. In the COVID-19, along with pulmonary symptoms, cardiovascular (CV) events were also recorded that have known to significantly contribute to the mortality. In our study, we designed and validated a new risk score that can predict CV events, and also evaluated the effect of these complications on the prognosis in COVID-19 patients. MATERIALS AND METHODS: A retrospective, multicenter, observational study was done among 1000 laboratory-confirmed COVID-19 patients between June 2020 and December 2020. All the data of the clinical and laboratory parameters were collected. Patients were randomly divided into two groups for testing and validating the hypothesis. The identification of the independent risk factors was done by the logistic regression analysis method. RESULTS: Of all the types of the clinical and laboratory parameters, ten "independent risk factors" were identified associated with CV events in Group A: male gender, older age, chronic heart disease, cough, lymphocyte count <1.1 × 109/L at admission, blood urea nitrogen >7 mmol/L at admission, estimated glomerular filtration rate <90 ml/min/1.73 m2 at admission, activated partial thromboplastin time >37 S, D-dimer, and procalcitonin >0.5 mg/L. In our study, we found that CV events were significantly related with inferior prognosis (P < 0.001). CONCLUSIONS: A new risk scoring system was designed in our study, which may be used as a predictive tool for CV complications among the patients with COVID-19 infection.

Evaluation of Eruption Pattern and Caries Occurrence among Children Affected with Fluorosis.

AIM: The aim of this study was to evaluate eruption pattern and occurrence of caries in children affected with fluorosis. MATERIALS AND METHODS: One hundred and fifty subjects (75 each with/without fluorosis) with age group of 7-8 years were selected. Dental fluorosis assessed on the buccal surfaces of the permanent incisors and molars and scored using the Thylstrup and Fejerskov index. The tooth were scored as emerged when at least one cusp of the tooth was visible in the mouth. Caries attack rate in primary and permanent teeth were estimated using DMFS and defs index in fluorosis patient. The findings were subjected to statistical analysis. The data were analyzed using Student "t" test and ANOVA "F" test. RESULTS: There was statistically highly significant difference found in the incidence of occlusal, mesioproximal, and distoproximal caries between fluorotic and nonfluorotic patients (p < 0.001). The result of present study showed a nonsignificant association between fluoride exposure parameter and median emergence ages of permanent incisors and molar teeth. On the other hand, caries occurrence shows a significant association with fluorosis. CONCLUSION: In this study, a significant positive correlation exists in the prevalence of caries and fluorosis. It is concluded that occlusal and proximal caries are less pronounced in fluorosis patients. CLINICAL SIGNIFICANCE: Dental caries is a public health problem. In this study, we study the fluoride effect since the predominant cariostatic effect of fluoride is beneficial in extensive caries reduction without a concomitant risk of dental fluorosis. How to cite this article: Trivedi S, Trivedi A, Banda NR, et al. Evaluation of Eruption Pattern and Caries Occurrence among Children Affected with Fluorosis. J Contemp Dent Pract 2019;20(10):1217-1222.