Selenium Nanoparticles: A Comprehensive Examination of Synthesis Techniques and Their Diverse Applications in Medical Research and Toxicology Studies.

Selenium is a trace and necessary micronutrient for human, animal, and microbial health. Many researchers have recently been interested in selenium nanoparticles (SeNPs) due to their biocompatibility, bioavailability, and low toxicity. As a result of their greater bioactivity, selenium nanoparticles are widely employed in a variety of biological applications. Physical, chemical, and biological approaches can all be used to synthesize selenium nanoparticles. Since it uses non-toxic solvents and operates at a suitable temperature, the biological technique is a preferable option. This review article addresses the processes implemented in the synthesis of SeNPs and highlights their medicinal uses, such as the treatment of fungi, bacteria, cancer, and wounds. Furthermore, we discuss the most recent findings on the potential of several biological materials for selenium nanoparticle production. The precursor, extract, process, time, temperature, and other synthesis criteria will be elaborated in conjunction with the product's physical properties (size, shape, and stability). The synergies of SeNP synthesis via various methods aid future researchers in precisely synthesizing SeNPs and using them in desired applications.

Analysis of stability for nut yield and ancillary traits in cashew (Anacardium occidentale L.).

Cashew is cultivated in varied agro-ecological regions of India and yield levels vary with regions. Therefore, to identify stable genotype for yield, 18 genotypes were tested in four environments for nut yield and ancillary traits during 2008 to 2018 in randomized block design with two replications. The data of 6th annual harvest and cumulative nut yield of six years was analyzed employing additive main effect and multiplicative interaction (AMMI) and genotype and genotype by environment (GGE) methods. Analysis of variance for 6th annual harvest indicated significant differences (p < 0.01) for eight traits. Environments varied significantly (p < 0.01) for seven traits. Genotype by environment (G × E) interactions were significant (p < 0.01) for all traits. Analysis of variance for cumulative yield revealed significant variations between genotypes, environments, G x E interactions. Interaction principal component analysis (IPCA) 1 (84.39%) and IPCA 2 (10.27%) together captured 95% of variability. Genotypes, environments and G × E interaction were accounted for 16.18%, 4.50% and 77.22% respectively of total variation. The environment Pilicode discriminated better while Vridhachalam was representative. BPP-8 and Vengulra-7 were the winning genotypes in Bhubaneswar while Kanaka and Priyanka in Pilicode, Vengurla-4 in Jhargram and UN-50 in Vridhachalam. Therefore, promoting cultivation of these winning genotypes in the corresponding environments is highly recommended to enhance cashew nut production. As per ASV (AMMI stability value,) K-22-1 was stable genotype followed by Bhubaneswar-1. As per YSI (yield stability index), Bhubaneswar-1 was stable and high yielding followed by K-22-1 and BPP-8. Thus stable genotypes identified in this study viz., K-22-1 and Bhuvaneswar-1 are recommended for cultivation in west and east regions of India which have most cashew growing areas for increasing the cashew nut production.

Antimicrobial Peptides (AMP) in the Cell-Free Culture Media of Xenorhabdus budapestensis and X. szentirmaii Exert Anti-Protist Activity against Eukaryotic Vertebrate Pathogens including Histomonas meleagridis and Leishmania donovani Species.

Anti-microbial peptides provide a powerful toolkit for combating multidrug resistance. Combating eukaryotic pathogens is complicated because the intracellular drug targets in the eukaryotic pathogen are frequently homologs of cellular structures of vital importance in the host organism. The entomopathogenic bacteria (EPB), symbionts of entomopathogenic-nematode species, release a series of non-ribosomal templated anti-microbial peptides. Some may be potential drug candidates. The ability of an entomopathogenic-nematode/entomopathogenic bacterium symbiotic complex to survive in a given polyxenic milieu is a coevolutionary product. This explains that those gene complexes that are responsible for the biosynthesis of different non-ribosomal templated anti-microbial protective peptides (including those that are potently capable of inactivating the protist mammalian pathogen Leishmania donovanii and the gallinaceous bird pathogen Histomonas meleagridis) are co-regulated. Our approach is based on comparative anti-microbial bioassays of the culture media of the wild-type and regulatory mutant strains. We concluded that Xenorhabdus budapestensis and X. szentirmaii are excellent sources of non-ribosomal templated anti-microbial peptides that are efficient antagonists of the mentioned pathogens. Data on selective cytotoxicity of different cell-free culture media encourage us to forecast that the recently discovered "easy-PACId" research strategy is suitable for constructing entomopathogenic-bacterium (EPB) strains producing and releasing single, harmless, non-ribosomal templated anti-microbial peptides with considerable drug, (probiotic)-candidate potential.

A rare case of metastatic malignant phyllodes tumor with osteosarcomatous differentiation presenting with intestinal obstruction.

Phyllodes tumors (PTs) are uncommon biphasic breast neoplasms constituting 0.5 to 1.0% of all breast tumors. Malignant PTs form a very small proportion of these and may metastasize, especially to the lungs and bones. Aggression and metastatic potential are accentuated in tumors exhibiting heterologous differentiation. Metastases to the gastrointestinal tract (GIT) have seldom been reported and are often confined to a segment of the digestive tract. In the absence of relevant clinical history, such patients presenting with gastrointestinal symptoms can lead to diagnostic perplexities. We report a unique case of a malignant PT with extensive osteosarcomatous differentiation and widespread metastases to the GIT.

Effectiveness of lasers in direct pulp capping among permanent teeth - A systematic review and meta-analysis.

Background: Laser-assisted direct pulp capping (DPC) has considerable advantages compared to traditional methods such as: decontaminant effect; hemostatic and coagulant effect; reduced rise in pulp temperature; reduction of intracavitary pressure; dentinal melting; and biostimulation effect. Objective: The aim of this study was to conduct a systematic review of the literature and meta-analysis to evaluate the effectiveness of laser as adjuvant therapy in DPC among permanent teeth. Methods: Research question was formulated based on the population, intervention, comparison, and outcomes strategy. A comprehensive electronic literature search was conducted through Cochrane, PubMed, and Google scholar using MeSH words, text words, and Boolean operators, independently by two reviewers. Based on the specified inclusion and exclusion criteria, the selected articles were subjected to quality assessment and the risk of bias (ROB) was evaluated. Cochrane ROB 2.0 and Risk Of Bias In Non-randomised Studies - of Interventions (ROBINS-I) tools were used to assess the ROB. Results: Initially, 45 studies recovered, 9 articles were selected for systematic review and 7 articles could be included in the meta-analysis. Teeth treated with low level laser therapy pulp capping therapy showed lower clinical/radiological failure as compared to nonlaser pulp capping therapy with an odds ratio of 0.24 (95% confidence interval = 0.15-0.38; Z = 6.15); and the difference between two groups was statistically significant (P < 0.00001). Discussion: This systematic review and meta-analysis included both the randomized and nonrandomized controlled trial (RCT). The non-RCTs had low ROB when compared to the RCTs included in the study. All included RCT studies met the inclusion and exclusion criteria, but some did not adequately describe their methods in detail. Conclusion: Based on the limited evidence, the results of the meta-analysis demonstrated DPC treatment could achieve better clinical outcomes with the aid of lasers.

Expression of membrane Hsp90 is a molecular signature of T cell activation.

Heat shock protein 90 (Hsp90) maintains cellular proteostasis during stress and has been under investigation as a therapeutic target in cancer for over two decades. We and others have identified a membrane expressed form of Hsp90 (mHsp90) that previously appeared to be restricted to rapidly proliferating cells exhibiting a metastatic phenotype. Here, we used HS-131, a fluor-tethered mHsp90 inhibitor, to quantify the effect of T cell activation on the expression of mHsp90 in human and mouse T cells. In cell-based assays, stimulation of human T cells induced a 20-fold increase in mHsp90 expression at the plasma membrane, suggesting trafficking of mHsp90 is regulated by TCR and inflammatory mediated signaling. Following injection of HS-131 in mouse models of human rheumatoid arthritis and inflammatory bowel disease, we detected localization of the probe at sites of active disease, consistent with immune cell invasion. Moreover, despite rapid hepatobiliary clearance, HS-131 demonstrated efficacy in reducing the mean clinical score in the CIA arthritis model. Our results suggest mHsp90 expression on T cells is a molecular marker of T cell activation and potentially a therapeutic target for chronic diseases such as rheumatoid arthritis.

Prevalence of endodontic flare-up following intracanal medicament placement in permanent teeth undergoing endodontic treatment - A systematic review.

Background: Endodontic flare-up can occur in teeth undergoing root canal treatment. Intracanal medicaments are most commonly used in between appointments to eliminate microbial flora in the canal. However, extrusion of medicaments in the periapical region can cause an inflammatory reaction leading to postoperative pain. Aim: The aim of this study was to evaluate the prevalence of endodontic flare-up following intracanal medicament placement in permanent teeth undergoing endodontic treatment. Study Design: A comprehensive search was done in MEDLINE through PubMed, Cochrane, EBSCOhost, and Google Scholar from July 31, 1999 to July 31, 2019 to identify randomized trials involving the use of intracanal medicaments in teeth undergoing root canal treatment. Methods: The titles and abstracts of all retrieved articles were screened by two independent reviewers, and irrelevant studies were excluded. Full texts of the eligible studies were obtained and thoroughly assessed. Seventeen randomized control trials comprising 2665 subjects were included. Statistical Analysis: Narrative synthesis was provided for the findings obtained from the studies, mainly focusing on the intervention details. Heterogeneity of the previously mentioned characteristics was assessed using the Chi-square test and I2 statistics. Results: Placement of intracanal medicament was not associated with the occurrence of pain. Conclusion: The present review suggests that intracanal medicament do not cause endodontic flare-up rather reduces inter-appointment pain during endodontic treatment.

Comparative evaluation of clinical performance of two self-etch adhesive systems with total-etch adhesive system in noncarious cervical lesions: An in vivo study.

BACKGROUND: The growing demands for esthetic restorations have stimulated intensive research in the field of adhesive dentistry. Dental adhesive systems are used to promote adhesion between composite resins and dental structure. In the fundamental principles of adhesion, the primary mechanism contributing to the formation of adhesion is micromechanical bonding between the restoration and the tooth. The bond strength of self-etching adhesives to dentin was found to be almost equal to that of total-etch adhesives. The aim of the present prospective, double-blind, randomized controlled clinical trial was to evaluate and compare the clinical performance of two self-etch adhesive systems with total-etch adhesive system in noncarious cervical lesions (NCCLs). MATERIALS AND METHODS: In each patient, three teeth were randomly assigned according to the adhesive system used to Group A (total-etch adhesive system), Group B (two-bottle self-etch adhesive system), and Group C (one-bottle self-etch adhesive system). The clinical efficacy of these adhesive systems was determined by evaluating the retention rate, marginal integrity, and postoperative sensitivity at the following three levels: baseline, 6 months, and 18 months by following the Modified USPHS criteria introduced by Vanherle et al. RESULTS: In the present study, the retention rate at 18 month in Group A, Group B, and Group C of 96%, 92%, and 92% was observed, respectively. A marginal integrity at 18 months was 88%, 80%, and 84% for Group A, Group B, and Group C, respectively. Postoperative sensitivity at 18 months was 16%, 12%, and 12% for Group A, Group B, and Group C, respectively. CONCLUSION: The clinical performance of total-etch and self-etch adhesive systems in NCCLs did not differ significantly with regard to the evaluated parameters - retention, marginal integrity, and postoperative sensitivity.

Cellular fatty acid synthase is required for late stages of HIV-1 replication.

BACKGROUND: Like all viruses, HIV-1 relies on host systems to replicate. The human purinome consists of approximately two thousand proteins that bind and use purines such as ATP, NADH, and NADPH. By virtue of their purine binding pockets, purinome proteins are highly druggable, and many existing drugs target purine-using enzymes. Leveraging a protein affinity media that uses the purine-binding pocket to capture the entire purinome, we sought to define purine-binding proteins regulated by HIV-1 infection. RESULTS: Using purinome capture media, we observed that HIV-1 infection increases intracellular levels of fatty acid synthase (FASN), a NADPH-using enzyme critical to the synthesis of de novo fatty acids. siRNA mediated knockdown of FASN reduced HIV-1 particle production by 80%, and treatment of tissue culture cells or primary PBMCs with Fasnall, a newly described selective FASN inhibitor, reduced HIV-1 virion production by 90% (EC50 = 213 nM). Despite the requirement of FASN for nascent virion production, FASN activity was not required for intracellular Gag protein production, indicating that FASN dependent de novo fatty acid biosynthesis contributes to a late step of HIV-1 replication. CONCLUSIONS: Here we show that HIV-1 replication both increases FASN levels and requires host FASN activity. We also report that Fasnall, a novel FASN inhibitor that demonstrates anti-tumor activity in vivo, is a potent and efficacious antiviral, blocking HIV-1 replication in both tissue culture and primary cell models of HIV-1 replication. In adults, most fatty acids are obtained exogenously from the diet, thus making FASN a plausible candidate for pharmacological intervention. In conclusion, we hypothesize that FASN is a novel host dependency factor and that inhibition of FASN activity has the potential to be exploited as an antiretroviral strategy.

A comparison of human dental pulp response to calcium hydroxide and Biodentine as direct pulp-capping agents.

CONTEXT: Direct pulp capping involves the placement of a biocompatible agent on pulp tissue that has been inadvertently exposed from traumatic injury or by iatrogenic means. AIM: To compare the human pulp response to calcium hydroxide and Biodentine as direct pulp-capping agents. MATERIALS AND METHODS: Pulp exposures were performed on the pulpal floor of forty human permanent premolars. The exposure sites were dressed with either Dycal or Biodentine as pulp-capping materials. After 45 days, teeth were extracted and processed for histological examination. STATISTICAL ANALYSIS: The histological data were subjected to Wilcoxon rank-sum test. RESULTS: The dentinal bridges in teeth that were capped with Biodentine were significantly thicker (P < 0.0001) and more continuous (P = 0.0001) with less pulpal inflammation (P = 0.0044) in comparison to Dycal. CONCLUSION: Based on the result of this study, Biodentine can be suggested as the material of choice for direct pulp capping procedure instead of Dycal. However, further long-term follow-up in vivo human studies using Biodentine on cariously exposed pulpal teeth are warranted to derive a definite conclusion.

Fasnall, a Selective FASN Inhibitor, Shows Potent Anti-tumor Activity in the MMTV-Neu Model of HER2(+) Breast Cancer.

Many tumors are dependent on de novo fatty acid synthesis to maintain cell growth. Fatty acid synthase (FASN) catalyzes the final synthetic step of this pathway, and its upregulation is correlated with tumor aggressiveness. The consequences and adaptive responses of acute or chronic inhibition of essential enzymes such as FASN are not fully understood. Herein we identify Fasnall, a thiophenopyrimidine selectively targeting FASN through its co-factor binding sites. Global lipidomics studies with Fasnall showed profound changes in cellular lipid profiles, sharply increasing ceramides, diacylglycerols, and unsaturated fatty acids as well as increasing exogenous palmitate uptake that is deviated more into neutral lipid formation rather than phospholipids. We also showed that the increase in ceramide levels contributes to some extent in the mediation of apoptosis. Consistent with this mechanism of action, Fasnall showed potent anti-tumor activity in the MMTV-Neu model of HER2(+) breast cancer, particularly when combined with carboplatin.

Management of synodontia between dilacerated permanent maxillary central incisor and supernumerary tooth with aid of cone-beam computed tomography.

A malformed tooth characterized by one or more developmental disturbances is often difficult to treat. When such teeth are present in anterior region, they pose a technical challenge for the clinician to restore esthetics as well as function. This case describes endodontic, surgical, and restorative management of fused and dilacerated maxillary central incisor. Cone-beam computed tomography (CBCT) was used in the present case to aid in understanding of complicated tooth morphology and managing the case successfully.

Cow's Milk Contamination of Human Milk Purchased via the Internet.

BACKGROUND: The US Food and Drug Administration recommends against feeding infants human milk from unscreened donors, but sharing milk via the Internet is growing in popularity. Recipient infants risk the possibility of consuming contaminated or adulterated milk. Our objective was to test milk advertised for sale online as human milk to verify its human origin and to rule out contamination with cow's milk. METHODS: We anonymously purchased 102 samples advertised as human milk online. DNA was extracted from 200 µL of each sample. The presence of human or bovine mitochondrial DNA was assessed with a species-specific real-time polymerase chain reaction assay targeting the nicotinamide adenine dinucleotide (NADH) dehydrogenase subunit 5 gene. Four laboratory-created mixtures representing various dilutions of human milk with fluid cow's milk or reconstituted infant formula were compared with the Internet samples to semiquantitate the extent of contamination with cow's milk. RESULTS: All Internet samples amplified human DNA. After 2 rounds of testing, 11 samples also contained bovine DNA. Ten of these samples had a level of bovine DNA consistent with human milk mixed with at least 10% fluid cow's milk. CONCLUSIONS: Ten Internet samples had bovine DNA concentrations high enough to rule out minor contamination, suggesting a cow's milk product was added. Cow's milk can be problematic for infants with allergy or intolerance. Because buyers cannot verify the composition of milk they purchase, all should be aware that it might be adulterated with cow's milk. Pediatricians should be aware of the online market for human milk and the potential risks.

Frequency of second mesiobuccal canal in permanent maxillary first molars using the operating microscope and selective dentin removal: A clinical study.

PURPOSE: The aim of this study was to investigate whether the combination of operating microscope and selective dentin removal increased the frequency of second mesiobuccal (MB2) canal detection in permanent maxillary first molar teeth. MATERIALS AND METHODS: One hundred fifty permanent maxillary first molars indicated for root canal treatment were randomly selected from patients belonging to the age group of 18-45 years irrespective of gender. After access cavity preparation and location of main canals, the MB2 canal orifice was sought in all teeth with an endodontic explorer under direct vision (Stage I), then under magnification with the aid of operating microscope (Stage II) and finally with the combined use of operating microscope and selective dentin removal (Stage III). RESULTS: MB2 canals were detected in 36%, 54% and 72% of the teeth in Stages I-III, respectively. CONCLUSION: This study demonstrated that dental operating microscope when used along with adjunctive aids such as selective dentin removal/troughing and good clinical knowledge will increase the ability of dental clinician to locate MB2 canals.

Signal transducer and activator of transcription 1 (STAT-1) plays a critical role in control of Trypanosoma cruzi infection.

The control of Trypanosoma cruzi infection is related to interferon-γ (IFN-γ) activation leading to intracellular clearance of parasites. The transcription factor signal transducer and activator of transcription 1 (STAT-1) is a key mediator of IFN-γ intracellular signalling and knockout of this protein leads to susceptibility to several intracellular microbes. To determine the role of STAT-1 in host susceptibility to T. cruzi infection we compared the survival, parasite loads and balance of IFN-γ and interleukin-10 (IL-10) responses between wild-type and STAT-1 knockout mice. We found that the lack of STAT-1 resulted in a more robust infection, leading to higher levels of blood and tissue parasites and markedly reduced survival. In addition, infected STAT-1 knockout mice had higher systemic levels of both IFN-γ and IL-10, suggesting that the absence of STAT-1 leads to a disequilibrium of pro-inflammatory and anti-inflammatory cytokines. Analysis of spleen cells indicates that CD4, CD8 cells generate IFN-γ and natural killer cells express IL-13 in STAT-1 knockout animals. The production of IL-17 is particularly enhanced in the absence STAT-1 expression but did not reduce mortality. Overall these results indicate that STAT-1 is important for the control of T. cruzi infection in mice.

Use of quartz fiber post for reattachment of complex crown root fractures: A 4-year follow-up.

Dental hard tissue trauma is among the most common cases encountered in dental practice. Simple tooth fractures, which occur due to sharp blows, are widely seen in all age groups, especially in young adults. If in case of complex fractures the fractured tooth fragments are available to the dentist in a clean and hydrated state, reattachment of the tooth fragment is the most conservative and biological treatment option possible. Cases of enamel and dentin fractures not involving pulp are treated by reattaching the fragment with adhesives and composite resin. However, fractures involving the pulp require reinforcement by quartz fiber posts and resin luting cement. In cases of fractures extending subgingivally, an envelope flap helps to achieve the desired isolation and visibility. This article presents 2 case reports of reattachment of fractured tooth fragments. The first case showing a 4-year success was treated without raising a flap. The second case with a subgingival fracture was treated by raising a flap. Reattachment is the most economical, biologically acceptable and esthetic restorative option for dental trauma.

Design of protease-resistant pexiganan enhances antileishmanial activity.

Antimicrobial peptides are increasingly being explored as alternative agents for therapy against the parasitic protozoan Leishmania. Previously, we reported that the synthetic magainin analog, pexiganan, induced apoptosis of surface protease-deficient Leishmania. Here, we report the development of an arginine-rich variant of this peptide which has reduced protease susceptibility and enhanced activity against wild type Leishmania in vitro. This peptide induces calcium delocalization and caspase 3/7 activity indicative of apoptosis, demonstrating that structural modification of pexiganan leads to drastic changes in biologic activity against Leishmania.

A rare root canal configuration of bilateral maxillary first molar with 7 root canals diagnosed using cone-beam computed tomographic scanning: a case report.

INTRODUCTION: The complexity of the root canal system of maxillary molars presents a constant challenge in the diagnosis and treatment of these teeth. This case report describes the importance of a surgical operating microscope and cone-beam computed tomographic (CBCT) imaging. METHODS: Root canal treatment of a left maxillary first molar with 3 roots and 7 canals was successfully performed. Seven canals were identified with the help of a surgical operating microscope and CBCT imaging. CBCT images also confirmed the 3 roots and 7 canals in the right maxillary first molar. RESULTS: CBCT images confirmed a type IV canal pattern in the distal and palatal root, whereas the mesial root had a type VIII canal pattern. CONCLUSIONS: The use of a surgical operating microscope and CBCT imaging helps the clinician to diagnose unusual anatomy of a tooth and facilitate successful endodontic treatment.