Repeated Silica exposures lead to Silicosis severity via PINK1/PARKIN mediated mitochondrial dysfunction in mice model.

BACKGROUND AND OBJECTIVES: Silicosis, one of the occupational health illnesses is caused by inhalation of crystalline silica. Deposition of extracellular matrix and fibroblast proliferation in lungs are linked to silicosis development. Mitochondrial dysfunction plays critical role in some diseases, but how these processes progress and regulated in silicosis, remains limited. Detailed study of silica induced pulmonary fibrosis in mouse model, its progression and severity may be helpful in designing future therapeutic strategies. METHODS: In present study, mice model of silicosis has been developed after repeated silica exposures which may closely resemble clinical symptoms of silicosis in human. In addition to efficiently mimicking the acute/chronic transformation processes of silicosis, this is practical and efficient in terms of time and output, which avoids mechanical injury to the upper respiratory tract due to surgical interventions. Sonicated sterile silica suspension (120 mg/kg) was administered through intranasal route thrice a week at regular intervals (21, 28 and 35 days). RESULTS: Presence of minute to larger silicotic nodules in H&E-stained lung sections were observed in all silica induced model groups. Enhanced ECM deposition was noted in MT stained lung sections of silica exposure groups as compared to control which were confirmed by significantly higher MMP9 expression levels and hydroxyproline content in silica 35 days group. Increase in Reactive oxygen species (ROS), inflammatory cell recruitment mainly, neutrophils and macrophage were observed in all three silica exposure groups. Transmission electron microscopic analysis has confirmed presence of many aberrant shaped mitochondria (swollen, round shape) in 35 days model where autophagosomes were minimum. Western blot analysis of mitophagy and autophagy markers such as Pink1, Parkin, Cytochrome c, SQSTM1/p62, the ratio of light chain LC3B II/LC3B I was found higher in 21 and 28 days which were significantly reduced in 35 days silica model. CONCLUSIONS: Higher MMP9 activity and MMP9 /TIMP1 ratio demonstrate excessive extracellular matrix damage and deposition in 35 days model. Significantly reduced expressions of autophagy and mitophagy markers have also confirmed progression in fibrosis severity and its association with repeated silica exposures in 35 days model group.

WNT-ß Catenin Signaling as a Potential Therapeutic Target for Neurodegenerative Diseases: Current Status and Future Perspective.

Wnt/ß-catenin (WßC) signaling pathway is an important signaling pathway for the maintenance of cellular homeostasis from the embryonic developmental stages to adulthood. The canonical pathway of WßC signaling is essential for neurogenesis, cell proliferation, and neurogenesis, whereas the noncanonical pathway (WNT/Ca2+ and WNT/PCP) is responsible for cell polarity, calcium maintenance, and cell migration. Abnormal regulation of WßC signaling is involved in the pathogenesis of several neurodegenerative diseases such as Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and spinal muscular atrophy (SMA). Hence, the alteration of WßC signaling is considered a potential therapeutic target for the treatment of neurodegenerative disease. In the present review, we have used the bibliographical information from PubMed, Google Scholar, and Scopus to address the current prospects of WßC signaling role in the abovementioned neurodegenerative diseases.

ABO blood types, but not Secretor or Lewis blood types, influence strength of antibody response to Hepatitis B vaccine in Black South African children.

Subunit vaccines for the Hepatitis B virus (HBV) have greatly reduced the prevalence of infection and morbidity through HBV-related liver cirrhosis and cancer. However, strength of immune response to vaccination varies considerably. While it is known that ABO blood types may influence HBV infection risk, the role of ABO and related blood types in strength of immune response to HBV vaccine has not been investigated. We examined 16 polymorphisms in the ABO, FUT2, and FUT3 genes and their related phenotypes for associations with strength of antibody response to HBV vaccine in Black South African infants. Anti-HBc and anti-HBs antibody levels were measured by CMIA assay 1-3 months after the last dose of HBV vaccine. Prior infection occurred in 8/207 individuals (3.86%) who were removed from further study. Of the remaining 199 individuals, 83.4% individuals were strong responders (anti-HBs ≥ 100 mIU/ml, median 973 mIU/ml), another 15.6% were weak responders (anti-HBs < 100 mIU/ml, median 50 mIU/ml) and 1% were non-responders (anti-HBs < 10 mIU/ml). The frequency of weak responders to HBV vaccine was not significantly affected by sex, birthweight, use of an additional booster dose of vaccine or cohort of origin. We characterised patterns of genetic variation present at the ABO, FUT2 and FUT3 loci by use of MassArray genotyping and used these data to predict ABO, Secretor and Lewis phenotypes. We observed significant association of ABO blood type with strength of antibody response to HBV vaccine in a Black South African cohort (p = 0.002). In particular, presence of rs8176747G and expression of B antigen (whether in B blood type or AB blood type) was associated with decreased antibody response to HBV vaccine. Secretor and Lewis blood types were not associated with antibody response to HBV vaccine. This work increases our understanding of the impact that host genetic variation may have on vaccine immunogenicity.

Biosynthesis and Bioapplications of Nanomaterials from Mushroom Products.

The production of nanoparticles (NPs) from chemical and physical synthesis has ended due to the involvement of toxic byproducts and harsh analytical conditions. Innovation and research in nanoparticle synthesis are derived from biomaterials that have gained attention due to their novel features, such as ease of synthesis, low-cost, eco-friendly approach, and high water solubility. Nanoparticles obtained through macrofungi involve several mushroom species, i.e., Pleurotus spp., Ganoderma spp., Lentinus spp., and Agaricus bisporus. It is well-known that macrofungi possess high nutritional, antimicrobial, anti-cancerous, and immune-modulatory properties. Nanoparticle synthesis via medicinal and edible mushrooms is a striking research field, as macrofungi act as an eco-friendly biofilm that secretes essential enzymes to reduce metal ions. The mushroom-isolated nanoparticles exhibit longer shelf life, higher stability, and increased biological activities. The synthesis mechanisms are still unknown; evidence suggests that fungal flavones and reductases have a significant role. Several macrofungi have been utilized for metal synthesis (such as Ag, Au, Pt, Fe) and non-metal nanoparticles (Cd, Se, etc.). These nanoparticles have found significant applications in advancing industrial and bio-medical ventures. A complete understanding of the synthesis mechanism will help optimize the synthesis protocols and control the shape and size of nanoparticles. This review highlights various aspects of NP production via mushrooms, including its synthesis from mycelium and the fruiting body of macrofungi. Also, we discuss the applications of different technologies in NP high-scale production via mushrooms.

Evaluation of Medical Certification of Cause of Death in Tertiary Cancer Hospitals in Northern India.

BACKGROUND: Medical certification of cause of death (MCCD) provides valuable data regarding disease burden in a community and for formulating health policy. Inaccurate MCCDs can significantly impair the precision of national health information. OBJECTIVE: To evaluate the accuracy of cause of death certificates prepared at two tertiary cancer care hospitals in Northern India during the study period (May 2018 to December 2020). METHOD: A retrospective observational study at two tertiary cancer care hospitals in Varanasi, India, over a period of two and a half years. Medical records and cause of death certificates of all decedents were examined. Demographic characteristics, administrative details and cause of death data were collected using the WHO recommended death certificates. Accuracy of death certification was validated by electronic medical records and errors were graded. RESULTS: A total of 778 deaths occurred in the two centres during the study period. Of these, only 30 (3.9%) certificates were error-free; 591 (75.9%) certificates had an inappropriate immediate cause of death; 231 (29.7%) certificates had incorrectly labelled modes of death as the immediate cause of death; and 585 (75.2%) certificates had an incorrect underlying cause of death. The majority of certificates were prepared by junior doctors and were significantly associated with higher certification errors. CONCLUSION: A high rate of errors was identified in death certification at the cancer care hospitals during the study period. Inaccurate MCCDs related to cancers can potentially influence cancer statistics and thereby affect policy making for cancer control. IMPLICATIONS: This study has identified the pressing need for appropriate interventions to improve quality of certification through training of doctors.

Exploring the Paradox of COVID-19 in Neurological Complications with Emphasis on Parkinson's and Alzheimer's Disease.

Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is a human coronavirus (HCoV) that has created a pandemic situation worldwide as COVID-19. This virus can invade human cells via angiotensin-converting enzyme 2 (ACE2) receptor-based mechanisms, affecting the human respiratory tract. However, several reports of neurological symptoms suggest a neuroinvasive development of coronavirus. SARS-CoV-2 can damage the brain via several routes, along with direct neural cell infection with the coronavirus. The chronic inflammatory reactions surge the brain with proinflammatory elements, damaging the neural cells, causing brain ischemia associated with other health issues. SARS-CoV-2 exhibited neuropsychiatric and neurological manifestations, including cognitive impairment, depression, dizziness, delirium, and disturbed sleep. These symptoms show nervous tissue damage that enhances the occurrence of neurodegenerative disorders and aids dementia. SARS-CoV-2 has been seen in brain necropsy and isolated from the cerebrospinal fluid of COVID-19 patients. The associated inflammatory reaction in some COVID-19 patients has increased proinflammatory cytokines, which have been investigated as a prognostic factor. Therefore, the immunogenic changes observed in Parkinson's and Alzheimer's patients include their pathogenetic role. Inflammatory events have been an important pathophysiological feature of neurodegenerative diseases (NDs) such as Parkinson's and Alzheimer's. The neuroinflammation observed in AD has exacerbated the Aß burden and tau hyperphosphorylation. The resident microglia and other immune cells are responsible for the enhanced burden of Aß and subsequently mediate tau phosphorylation and ultimately disease progression. Similarly, neuroinflammation also plays a key role in the progression of PD. Several studies have demonstrated an interplay between neuroinflammation and pathogenic mechanisms of PD. The dynamic proinflammation stage guides the accumulation of α-synuclein and neurodegenerative progression. Besides, few viruses may have a role as stimulators and generate a cross-autoimmune response for α-synuclein. Hence, neurological complications in patients suffering from COVID-19 cannot be ruled out. In this review article, our primary focus is on discussing the neuroinvasive effect of the SARS-CoV-2 virus, its impact on the blood-brain barrier, and ultimately its impact on the people affected with neurodegenerative disorders such as Parkinson's and Alzheimer's.

Effect of process parameters on the ß-galactosidase hydrolysis of lactose and galactooligosaccharide formation in concentrated skim milk.

The study aimed at evaluation of ß-galactosidase activity for lactose hydrolysis (DH) and galactooligosaccharide (GOS) formation at 7 °C. ß-galactosidase derived from K. lactis was more effective than B. lichenformis for DH and GOS formation in 16% lactose solution. ß-galactosidase from K. lactis exhibited 96.61% DH and 7.28% GOS production after 12 h of reaction and hence was utilized for lactose hydrolysis in concentrated skim milk (40% total solids). Use of 9.53 U/mL enzyme resulted in significantly high DH (97.06%) after 12 h with 4.90 g/L of residual lactose. However, maximum GOS formation of 12.01% with 94.74% DH was obtained after 4 h. Further increase in reaction time up to 12 h resulted in breakdown of tri and tetrasaccharide GOS, thereby, reducing GOS content. Hence, reaction time of 12 h was finalized to obtain maximum DH along with additional benefit of GOS formation.

Therapeutic Potential of Vital Transcription Factors in Alzheimer's and Parkinson's Disease With Particular Emphasis on Transcription Factor EB Mediated Autophagy.

Autophagy is an important cellular self-digestion and recycling pathway that helps in maintaining cellular homeostasis. Dysregulation at various steps of the autophagic and endolysosomal pathway has been reported in several neurodegenerative disorders such as Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington disease (HD) and is cited as a critically important feature for central nervous system (CNS) proteostasis. Recently, another molecular target, namely transcription factor EB (TFEB) has been explored globally to treat neurodegenerative disorders. This TFEB, is a key regulator of autophagy and lysosomal biogenesis pathway. Multiple research studies suggested therapeutic potential by targeting TFEB to treat human diseases involving autophagy-lysosomal dysfunction, especially neurodegenerative disorders. A common observation involving all neurodegenerative disorders is their poor efficacy in clearing and recycle toxic aggregated proteins and damaged cellular organelles due to impairment in the autophagy pathway. This dysfunction in autophagy characterized by the accumulation of toxic protein aggregates leads to a progressive loss in structural integrity/functionality of neurons and may even result in neuronal death. In recent years TFEB, a key regulator of autophagy and lysosomal biogenesis, has received considerable attention. It has emerged as a potential therapeutic target in numerous neurodegenerative disorders like AD and PD. In various neurobiology studies involving animal models, TFEB has been found to ameliorate neurotoxicity and rescue neurodegeneration. Since TFEB is a master transcriptional regulator of autophagy and lysosomal biogenesis pathway and plays a crucial role in defining autophagy activation. Studies have been done to understand the mechanisms for TFEB dysfunction, which may yield insights into how TFEB might be targeted and used for the therapeutic strategy to develop a treatment process with extensive application to neurodegenerative disorders. In this review, we explore the role of different transcription factor-based targeted therapy by some natural compounds for AD and PD with special emphasis on TFEB.

The Role of Vitamins in Neurodegenerative Disease: An Update.

Acquiring the recommended daily allowance of vitamins is crucial for maintaining homeostatic balance in humans and other animals. A deficiency in or dysregulation of vitamins adversely affects the neuronal metabolism, which may lead to neurodegenerative diseases. In this article, we discuss how novel vitamin-based approaches aid in attenuating abnormal neuronal functioning in neurodegeneration-based brain diseases such as Alzheimer's disease, Parkinson's disease, Huntington's disease, Amyotrophic lateral sclerosis, and Prion disease. Vitamins show their therapeutic activity in Parkinson's disease by antioxidative and anti-inflammatory activity. In addition, different water- and lipid-soluble vitamins have also prevented amyloid beta and tau pathology. On the other hand, some results also show no correlation between vitamin action and the prevention of neurodegenerative diseases. Some vitamins also exhibit toxic activity too. This review discusses both the beneficial and null effects of vitamin supplementation for neurological disorders. The detailed mechanism of action of both water- and lipid-soluble vitamins is addressed in the manuscript. Hormesis is also an essential factor that is very helpful to determine the effective dose of vitamins. PubMed, Google Scholar, Web of Science, and Scopus were employed to conduct the literature search of original articles, review articles, and meta-analyses.

Therapeutic applications of mushrooms and their biomolecules along with a glimpse of in silico approach in neurodegenerative diseases.

Neurodegenerative diseases (NDs) represent a common neurological pathology that determines a progressive deterioration of the brain or the nervous system. For treating NDs, comprehensive and alternative medicines have attracted scientific researchers' attention recently. Edible mushrooms are essential for preventing several age-based neuronal dysfunctions such as Parkinson's and Alzheimer's diseases. Mushroom such as Grifola frondosa, Lignosus rhinocerotis, Hericium erinaceus, may improve cognitive functions. It has also been reported that edible mushrooms (basidiocarps/mycelia extracts or isolated bioactive compounds) may reduce beta-amyloid-induced neurotoxicity. Medicinal mushrooms are being used for novel and natural compounds that help modulate immune responses and possess anti-cancer, anti-microbial, and anti-oxidant properties. Compounds such as polyphenols, terpenoids, alkaloids, sesquiterpenes, polysaccharides, and metal chelating agents are validated in different ND treatments. This review aims to assess mushrooms' role and their biomolecules utilization for treating different kinds of NDs. The action mechanisms, presented here, including reducing oxidative stress, neuroinflammation, and modulation of acetylcholinesterase activity, protecting neurons or stimulation, and regulating neurotrophins synthesis. We also provide background about neurodegenerative diseases and in-silico techniques of the drug research. High costs associated with experiments and current ethical law imply efficient alternatives with limited cost value. In silico approaches provide an alternative method with low cost that has been successfully implemented to cure ND disorders in recent days. We also describe the applications of computational procedures such as molecular docking, virtual high-throughput screening, molecular dynamic (MD) simulation, quantum-mechanical methods for drug design. They were reported against various targets in NDs.

Promising drug targets and associated therapeutic interventions in Parkinson's disease.

Parkinson's disease (PD) is one of the most debilitating brain diseases. Despite the availability of symptomatic treatments, response towards the health of PD patients remains scarce. To fulfil the medical needs of the PD patients, an efficacious and etiological treatment is required. In this review, we have compiled the information covering limitations of current therapeutic options in PD, novel drug targets for PD, and finally, the role of some critical beneficial natural products to control the progression of PD.

Mucuna pruriens in Parkinson's and in some other diseases: recent advancement and future prospective.

Mucuna pruriens (Mp) is an annual and perennial legume which belongs to the family Fabaceae having different types of therapeutic activity. Anti-oxidative, anti-inflammatory, anti-epileptic, anti-microbial, etc. are the example of some most common activities of Mp. It is widely utilized as a potent aphrodisiac. The anti-Parkinsonian activity of Mp was explored since the nineteenth century. The neuroprotective activity of Mp was shown by several researchers. Levodopa (L-DOPA) is the important constituents responsible for the anti-Parkinsonian activity of Mp. Apart from L-DOPA, several other important bioactive components like Ursolic acid (UA) and Betulinic acid (BA) also exhibit a similar neuroprotective activity. Parkinson's disease (PD) is mainly sporadic. A very small proportion shows the genetic nature of PD. The anti-Parkinsonian activity of Mp was explored in different toxin-induced PD models as like MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), Rotenone, Paraquat, 6-hydroxydopamine (6-OHDA) as suggested by several pieces of literature. Various parts of Mp's like seed, leaf, and stem exhibit potent neuroprotective attributes. Among different parts, seeds are widely utilized as anti-PD agents because of the higher percentage of L-DOPA. Besides anti-PD activity, Mp's neuroprotective potential was also explored in the ischemic model of stroke that also shows positive results. Recently, several clinical trials have been performed on the anti-PD activity of Mp on PD patients that show convincing results. Although, a small population-based study needs to be further validated in the broader population. Apart from anti-PD activity, Mp also shows its therapeutic activity in some other diseases like cancer, diabetes, skin infection, anemia, antihypertensive, etc. that are summarized in Table 1. In this review, we have discussed the anti-PD potential of Mp in the sporadic and genetic model along with some clinical trials that have performed on PD patients. Some other activity of Mp is also summarized in this review. There is a strong need to test the efficacy of Mp in some other neurodegenerative diseases along with PD. Following this, this review emphasizes the role of Mp in PD systematically through literature analysis available to date. [Table: see text].

Advancement in the modelling and therapeutics of Parkinson's disease.

Since the discovery of L-dopa in the middle of the 20th century (1960s), there is not any neuroprotective therapy available although significant development has been made in the treatment of symptomatic Parkinson's disease (PD). Neurological disorders like PD can be modelled in animals so as to recapitulates most of the symptoms seen in PD patients. In aging population, PD is the second most common neurodegenerative disease after Alzheimer's disease, even though significant outcomes have been achieved in PD research yet it still is a mystery to solve the treatments for PD. In the last two decades, PD models have provided enhanced precision into the understanding of the process of PD disease, its etiology, pathology, and molecular mechanisms behind it. Furthermore, at the same time as cellular models have helped to recognize specific events, animal models, both toxic and genetic, have replicated almost all of the hallmarks of PD and are very helpful for testing and finding new strategies for neuroprotection. Recently, in both classical and newer models, major advances have been done in the modelling of supplementary PD features have come into the light. In this review, we have try to provide an updated summary of the characteristics of these models related to in vitro and in vivo models, animal models for PD, stem cell model for PD, newer 3D model as well as the strengths and limitations of these most popular PD models.

Antioxidant and antibacterial activity of silver nanoparticles synthesized by Cestrum nocturnum.

BACKGROUND: Silver nanoparticles are toxic to bacteria and have widespread application in different research areas. OBJECTIVE: The aim of this study was to synthesize silver nanoparticles using an aqueous leaf extract of Cestrum nocturnum and to test its antioxidant and antibacterial activities. MATERIALS AND METHODS: The silver nanoparticles were synthesized by addition of 20 ml extract (8% w/v) with 180 ml silver nitrate solution (1 mM). The synthesis of silver nanoparticles was confirmed by UV-Vis spectrophotometer. The silver nanoparticles were characterized by X-ray diffractometer, Transmission Electron Microscope, Scanning Electron Microscope and Fourier Transform Infra-Red spectroscopy. The antioxidant property of silver nanoparticles was analyzed by the 2, 2-diphenyl-1-picrylhydrazyl, hydrogen peroxide, hydroxyl radical and superoxide radical scavenging methods. The bacteriostatic and bactericidal activity of silver nanoparticles against Escherichiacoli, Enterococcusfaecalis, and Salmonellatyphi was determined using bacterial growth inhibition method. The antibacterial sensitivity and Minimum Inhibitory Concentration (MIC) of silver nanoparticles was determined against the bacteria. RESULTS: The results confirmed that the silver nanoparticles synthesized by C.nocturnum extract were crystalline in nature, average particle size was 20 nm and were mostly spherical in shape. The antioxidant methods confirmed that the silver nanoparticles have more antioxidant activity as compared to vitamin C. The silver nanoparticles have strong antibacterial (maximum Vibrio cholerae and minimum E. faecalis) activity. The MIC value of silver nanoparticles was 16 µg/ml (Citrobacter), 4 µg/ml (E. faecalis), 16 µg/ml (S. typhi), 8 µg/ml (E. coli), 8 µg/ml (Proteusvulgaris), and 16 µg/ml (V. cholerae). CONCLUSION: Green synthesized silver nanoparticles have strong antioxidant and antibacterial activity due to the presence of bioactive molecules on the surface of silver nanoparticles.

Riboswitch regulation in cyanobacteria is independent of their habitat adaptations.

Cyanobacteria are one of the ancient bacterial species occupying a variety of habitats with diverse metabolic preferences. RNA regulators like riboswitches play significant role in controlling the gene expression in prokaryotes. The taxonomic distribution of riboswitches suggests that they might be one of the oldest mechanisms of gene control system. In this paper, we analyzed the distribution of different riboswitch families in various cyanobacterial genomes. It was observed that only four riboswitch classes were abundant in cyanobacteria, B12-element (Cob)/AdoCbl/AdoCbl-variant riboswitch being the most abundant. The analysis suggests that riboswitch mode of regulation is present in cyanobacterial species irrespective of their habitat types. A large number of unidentified genes regulated by riboswitches listed in this analysis indicate the wide range of targets for these riboswitch families. The analysis revealed a large number of genes regulated by riboswitches which may assist in elaborating the diversity among the cyanobacterial species.

Effect of dentin biomodifiers on the immediate and long-term bond strengths of a simplified etch and rinse adhesive to dentin.

OBJECTIVES: This in vitro study evaluated the effect of dentin biomodifiers on the immediate and long-term bond strengths of a simplified etch and rinse adhesive to dentin. MATERIALS AND METHODS: Flat coronal dentin surfaces were prepared in 120 extracted human molars. Teeth were randomly divided into 5 groups (n = 24) according to 5 different surface pre-treatments: No pre-treatment (control); 1M carbodiimide (EDC); 0.1% epigallocatechin-3-gallate (EGCG); 2% minocycline (MI); 10% sodium ascorbate (SA). After surface pre-treatment, adhesive (Adper Single Bond 2 [SB], 3M ESPE) was applied. Composite was applied into transparent plastic tubes (2.5 mm in diameter), which was placed over the bonded dentin surface. From each group, 10 samples were subjected to shear bond strength (SBS) evaluation at 24 hours (immediate) and remaining 10 samples were tested after 6 months (delayed). Additionally, 4 samples per group were subjected to scanning electron microscopic analysis for observation of resin-dentin interface. The data were statistically analysed with Shaperio­Wilk W test, 2-way analysis of variance (ANOVA), and post hoc Tukey's test. RESULTS: At 24 hours, SBS of all surface pre-treatment groups were comparable with the control group, with significant differences found between EDC and SA groups only (p = 0.009). After 6 months storage, EDC, EGCG, and MI pre-treatments preserved the resin-dentin bond strength with no significant fall. CONCLUSIONS: Dentin pre-treatment with all the dentin biomodifiers except SA resulted in significant preservation of resin-dentin bond over 6 months storage period, without negatively affecting the immediate bond strength of the etch and rinse adhesive tested.

Enhanced chemoprevention by the combined treatment of pterostilbene and lupeol in B[a]P-induced mouse skin tumorigenesis.

The present study is aimed to evaluate the inhibitory effect of the combination of two phytochemicals; pterostilbeneand lupeol (generally obtained from blue berries, grapes, white cabbage, green pepper, olive and mangoes) on mouse skin tumorigenesis. We hypothesized that the concomitant topical treatment of selected phytochemicals would lead to improved impediment of skin cancer. Swiss albino mice (n = 25) received a topical dose of Benzo[a]pyrene (B[a]P, 5 µg/animal) with pre/post application of pterostilbene (16 µM/0.2 ml acetone/animal) and/or lupeol (500 µM/0.2 ml acetone/animal) for 32 weeks. Results showed that pterostilbene and/or lupeol treatment resulted in a significant delay in onset of tumorigenesis. However, a more promising effect on tumor suppression was noted with the combination of both the phytochemicals. A significant reduction in average tumor volume, cumulative number of tumors and tumor multiplicity was recorded in combination treated group. The histopathological analysis illustrated the marked suppression in epidermal hyperplasia and necrotic cells in combination treated groups. Our study suggests that the combination of pterostilbene and lupeol was more effective in prevention of skin cancer as compared to either of the phytochemical alone. Therefore, the combined treatment of phytochemicals has better potential to prevent skin carcinogenesis.

Effect of carbodiimide on the structural stability of resin/dentin interface.

Clinical longevity of composite resin restorations is a significant problem in adhesive dentistry. Most of the current simplified adhesives present good immediate bonding, but the bond strength gradually falls over a period due to biodegradation at the resin-dentin interface. Various strategies have been proposed to improve the durability of resin-dentin bond including the use of matrix metalloproteinases inhibitors and collagen cross-linkers, biomimetic remineralization, ethanol wet bonding, to improve the physical and mechanical properties of the bonding substrate, i.e., dentin. However, all are under preliminary research and without any conclusive evidence. Therefore, this paper addresses the current challenge in dental adhesion, i.e., poor durability of resin-dentin bond and introduces the concept of dentin biomodification as an alternative way for improving the long-term bonding effectiveness of current adhesives to dentin and also provides an overview of a synthetic collagen cross-linking agent carbodiimide (EDC) including its mechanism of action, literature review of studies evaluating EDC, variables associated with its use and its cytotoxicity. Search was performed across the electronic databases (PubMed, Ebsco host, and Google search engine) to identify manuscripts for inclusion, using the keywords: carbodiimide, dentin bonding, durability, resin-dentin interface, and collagen cross-linking. Thirty-five articles were finally included, and the last search was made in February 2016.

Influence of double application technique on the bonding effectiveness of self-etch adhesive systems.

AIM: To evaluate and compare the effect of double-application of single-step self-etch adhesives using microleakage study and to analyze the dentin-adhesive interfacial micromorphology. METHODS: In total, 72 extracted human premolars were divided into three groups for different self-etch adhesives (G Bond, GC [GB], Optibond, Kerr [OB], and Xeno V Plus, Dentsply [XV]). Class V cavities were prepared. Each group was further divided into two subgroups (n = 10) according to the placement technique of the adhesive, using the single-application [subgroup (a)] or double-application method [subgroup (b)]. Resin composite (Z 250, 3M ESPE, St. Paul, MN) was used to restore the cavities and light cured for 40 s. Twenty samples from each group were subjected to microleakage study. Two samples from both the subgroups of the three adhesives were used for scanning electron microscopic examination of the resin-dentin interfacial ultrastructure. Dye leakage scores were subjected to statistical analysis using Kruskal-Wallis and Mann-Whitney U-tests at significance level of P < 0.05. RESULTS: GB depicted significantly more microleakage which was significantly greater than OB and XV. The double application led to significant decrease in microleakage of GB with no significant effect on the microleakage scores of other two all-in-one adhesives, that is OB and XV. CONCLUSION: Double application of all-in-one self-etch adhesives improves the marginal sealing ability in dentin although it appears to be product dependent.