Disrupted degradative sorting of TLR7 is associated with human lupus.

Hyperactive TLR7 signaling has long been appreciated as driver of autoimmune disease in mouse models. Recently, gain-of-function mutations in TLR7 were identified as a monogenic cause of human lupus. TLR7 is an intracellular transmembrane receptor, sensing RNA breakdown products within late endosomes. Here, we show that endosome dysfunction leads to unrestricted TLR7 signaling and is associated with human lupus. The late endosomal BORC complex together with the small GTPase Arl8b controls intracellular TLR7 levels by regulating receptor turnover. This requires a direct interaction between the TLR7-associated trafficking factor Unc93b1 and Arl8b. We identified an UNC93B1 mutation in a patient with childhood-onset lupus, which results in reduced BORC interaction and endosomal TLR7 accumulation. Therefore, a failure to control TLR7 turnover is sufficient to break immunological tolerance to nucleic acids. Our results highlight the importance of an intact endomembrane system in preventing pathological TLR7 signaling and autoimmune disease.

Outcome of severe leptospirosis presenting with ARDS in respiratory ICU.

Introduction: Acute Respiratory Distress Syndrome (ARDS) is a rare presentation and a major complication of leptospirosis associated with high mortality despite advances in management. Methods: We conducted a retrospective observational study, in 48 patients presenting with ARDS due to leptospirosis. Clinical presentation, risk factors, management and outcome of patients were noted. Factors associated with survival and mortality were studied. Results: Our study showed a male preponderance (87%) with a mean age of presentation of 31.5 years. All patients presented with multiorgan failure. PaO2/FiO2 ratio less than 100 on 3rd day was associated with 90% mortality. The requirement for invasive mechanical ventilation carried a mortality risk of 70.4%. Overall mortality was 39.6%. Conclusion: Leptospirosis can cause serious ARDS with a high case fatality. Prompt treatment with non-invasive mechanical ventilation to maintain haemodynamic stability and intravenous steroids can improve the outcome.

A case of post renal transplant PTLD of lung.

Post Transplant Lymphoproliferative Disorder (PTLD) is a heterogeneous group of Lymphoid proliferative disorders that occur in patients post Hematogenous or Solid organ transplants. They are closely associated with Ebstein-Barr Virus and can range from polyclonal lesions to frank lymphomas. PTLD is usually a rare post-transplant complication, with the incidence being higher post Lung or Heart Transplantation and less commonly seen post-renal transplantation. The incidence post renal transplantation is less than 1%, with most of the cases being limited to the Gastro-Intestinal Tract and Lymph nodes, and incidence in the lungs being extremely rare. Here we present a case report of PTLD of the lung in a post-renal transplant recipient.

Nanotechnology in Cosmetics and Cosmeceuticals-A Review of Latest Advancements.

Nanotechnology has the potential to generate advancements and innovations in formulations and delivery systems. This fast-developing technology has been widely exploited for diagnostic and therapeutic purposes. Today, cosmetic formulations incorporating nanotechnology are a relatively new yet very promising and highly researched area. The application of nanotechnology in cosmetics has been shown to overcome the drawbacks associated with traditional cosmetics and also to add more useful features to a formulation. Nanocosmetics and nanocosmeceuticals have been extensively explored for skin, hair, nails, lips, and teeth, and the inclusion of nanomaterials has been found to improve product efficacy and consumer satisfaction. This is leading to the replacement of many traditional cosmeceuticals with nanocosmeceuticals. However, nanotoxicological studies on nanocosmeceuticals have raised concerns in terms of health hazards due to their potential skin penetration, resulting in toxic effects. This review summarizes various nanotechnology-based approaches being utilized in the delivery of cosmetics as well as cosmeceutical products, along with relevant patents. It outlines their benefits, as well as potential health and environmental risks. Further, it highlights the regulatory status of cosmeceuticals and analyzes the different regulatory guidelines in India, Europe, and the USA and discusses the different guidelines and recommendations issued by various regulatory authorities. Finally, this article seeks to provide an overview of nanocosmetics and nanocosmeceuticals and their applications in cosmetic industries, which may help consumers and regulators to gain awareness about the benefits as well as the toxicity related to the continuous and long-term uses of these products, thus encouraging their judicious use.

A Review of Adsorbents for Heavy Metal Decontamination: Growing Approach to Wastewater Treatment.

Heavy metal is released from many industries into water. Before the industrial wastewater is discharged, the contamination level should be reduced to meet the recommended level as prescribed by the local laws of a country. They may be poisonous or cancerous in origin. Their presence does not only damage people, but also animals and vegetation because of their mobility, toxicity, and non-biodegradability into aquatic ecosystems. The review comprehensively discusses the progress made by various adsorbents such as natural materials, synthetic, agricultural, biopolymers, and commercial for extraction of the metal ions such as Ni2+, Cu2+, Pb2+, Cd2+, As2+ and Zn2+ along with their adsorption mechanisms. The adsorption isotherm indicates the relation between the amount adsorbed by the adsorbent and the concentration. The Freundlich isotherm explains the effective physical adsorption of the solute particle from the solution on the adsorbent and Langmuir isotherm gives an idea about the effect of various factors on the adsorption process. The adsorption kinetics data provide valuable insights into the reaction pathways, the mechanism of the sorption reaction, and solute uptake. The pseudo-first-order and pseudo-second-order models were applied to describe the sorption kinetics. The presented information can be used for the development of bio-based water treatment strategies.

Nanocellulose-Based Biomedical Scaffolds in Future Bioeconomy: A Techno-Legal Assessment of the State-of-the-Art.

Nanocellulose is a broader term used for nano-scaled cellulosic crystal and/or fibrils of plant or animal origin. Where bacterial nanocellulose was immediately accepted in biomedicine due to its "cleaner" nature, the plant-based nanocellulose has seen several roadblocks. This manuscript assesses the technological aspects (chemistry of cellulose, nanocellulose producing methods, its purity, and biological properties including toxicity and suggested applications in final drug formulation) along with legal aspects in REACH (Registration, Evaluation, Authorization, and Restriction of Chemicals) regulation by the European Union, EMA (European Medicine Agency). The botanical biomass processing methods leading to the nanoscale impurity (lignin and others) on nanocellulose surface, along with surface modification with harsh acid treatments are found to be two major sources of "impurity" in botanical biomass derived nanocellulose. The status of nanocellulose under the light of REACH regulation along with EMA has been covered. The provided information can be directly used by material and biomedical scientists while developing new nanocellulose production strategies as well as formulation design for European markets.

Assessing the potential of lignin nanoparticles as drug carrier: Synthesis, cytotoxicity and genotoxicity studies.

Lignin nanoparticles synthesis is among recent developments in lignin valorization especially for biomedical applications. In this study, a new technique where complete self-assembling of lignin was ensured by simultaneous solvent displacement and flash pH change was used to optimize particle size of blank lignin nanoparticles (BLNPs) for suitability in cell uptake along with maximized yield. To establish BLNPs as drug carrier, safety studies including hemocompatibility, cytotoxicity and elaborate genotoxicity studies on Drosophila melanogaster as a model organism were done. Finally, irinotecan loaded lignin nanoparticles (DLNPs) were synthesized to establish their drug carrying potential and thorough in vitro characterization was performed. BLNPs with controllable size (⁓152 nm), low polydispersity (<0.2), maximized yield (>65%), negative surface charge (-22 to -23 mV), spherical shape and smooth surface were obtained with acceptable %hemolysis (<2%). In vitro cytotoxicity studies revealed that BLNPs were significantly toxic (74.38 ± 4.74%) in human breast adenocarcinoma (MCF-7), slightly toxic (38.8 ± 4.70%) in human alveolar epithelial adenocarcinoma (A-549) and insignificantly toxic (15.89 ± 2.84%) to human embryonic kidney (HEK-293) cells. BLNPs showed concentration dependent early neuronal defects in Drosophila, but nuclei fragmentation and gut cell damage were absent. Sustained release DLNPs with high drug loading reduced the IC50 value of irinotecan by almost 3 folds.

Wood-Based Cellulose Nanofibrils: Haemocompatibility and Impact on the Development and Behaviour of Drosophila melanogaster.

Wood-based cellulose nanofibrils (CNF) offer an excellent scaffold for drug-delivery formulation development. However, toxicity and haemocompatibility of the drug carrier is always an important issue. In this study, toxicity-related issues of CNF were addressed. Different doses of CNF were orally administered to Drosophila and different tests like the developmental cycle, trypan blue exclusion assay, larva crawling assay, thermal sensitivity assay, cold sensitivity assay, larval light preference test, climbing behaviour, nitroblue tetrazolium (NBT) reduction assay, adult phenotype, and adult weight were conducted to observe the impact on its development and behaviour. A haemocompatibility assay was done on the blood taken from healthy Wistar rats. In Drosophila, the abnormalities in larval development and behaviour were observed in the behavioural assays. However, the cytotoxic effect could not be confirmed by the gut staining and level of reactive oxygen species. The larvae developed into an adult without any abnormality in the phenotype. The CNF did cause loss of weight in the adult flies and did not cause much toxicity within the body since there was no phenotypic defect. Hemolysis data also suggested that CNF was safe at lower doses, as the data was well within acceptable limits. All these results suggest that cellulose nanofibres have no significant cytotoxic effects on Drosophila. However, the developmental and behavioural abnormalities suggest that CNF may act as a behavioural teratogen.

Structure, Genome, Infection Cycle and Clinical Manifestations Associated with Human Papillomavirus.

A small, non-enveloped, obligatory parasite, Human papillomavirus (HPV) is known to be the cause of a range of malignancies. These entail benign infections like genital warts as well as malignant, life-threatening conditions such as cervical cancer. Since a very high mortality rate is associated with HPV caused cancers (cervical cancer is a 2nd leading cause of death caused due to cancer among women globally), there is an escalating need to understand and search for ways to combat such medical conditions. Under the same light, the given article provides an insight into the world of this versatile pathogen. Distinct aspects related to HPV have been discussed here. Emphasis has been laid upon the composition, function and assembly of capsid proteins (structural studies) and various genetic elements and their gene products (genomic studies). The essence of the mechanism behind the development of persistent infection and modes responsible for the transmission of the infectious particles has been briefly covered. Finally, the review outlines various infections and diseases caused by HPV with a major focus on their clinical and histological manifestations.

Co-Delivery of Eugenol and Dacarbazine by Hyaluronic Acid-Coated Liposomes for Targeted Inhibition of Survivin in Treatment of Resistant Metastatic Melanoma.

While melanoma remains a challenge for oncologists, possibilities are being continuously explored to fight resistant metastatic melanoma more effectively. Eugenol is reported to inhibit survivin protein in breast cancer cells. Survivin is also overexpressed by melanoma cells, and is known to impart resistance to them against chemotherapy-induced apoptosis. To be able to fight resistant melanoma, we formulated hyaluronic acid (HA)-coated liposomes loaded with an effective combination of anti-melanoma agents (Dacarbazine and Eugenol), using a solvent injection method. Quality-by-Design (QbD) was applied to optimize and obtain a final formulation with the desired quality attributes, and within an acceptable size range. The optimized formulation was then subjected to performance analysis in cell lines. Coated-Dacarbazine Eugenol Liposomes were found to possess 95.08% cytotoxicity at a dacarbazine concentration of 0.5 µg/mL, while Dacarbazine Solution showed only 10.20% cytotoxicity at the same concentration. The number of late apoptotic cells was also found to be much higher (45.16% vs. 8.43%). Furthermore, migration assay and proliferation study also revealed significantly higher inhibition of cell migration and proliferation by Coated-Dacarbazine Eugenol Liposomes, signifying its potential against metastasis. Thus, surface-functionalized dacarbazine- and eugenol-loaded liposomes hold great promise against resistant and aggressive metastatic melanoma, with much less unwanted cytotoxicity and reduced doses of the chemotherapeutic agent.

Novel 4-in-1 strategy to combat colon cancer, drug resistance and cancer relapse utilizing functionalized bioinspiring lignin nanoparticle.

Colon cancer is one of the fatal forms of cancer all round the world with a equal frequency of occurrence in both male and female population. Mutational changes and defects in APC (Adenomatous Polyposis Coli) and DNA mismatch repair genes accompanied by genetic chaos in oncogenic pathways leads to colon cancer. Intensive study on pathogenesis of colon cancer has been made to decipher the mechanisms underlying the development and progress of the disease so as to develop effective treatment. However, a complete therapeutic regimen is still not available for combating this deadly disease. Hurdles faced by chemotherapy include drug resistance due to P-glycoprotein transporters, untoward effects on normal cells, high cost, bio-burden of the therapy, and the most dreadful drawback is cancer relapse. The concept of cancer relapse is related to development of oxidative stress that causes cell apoptosis. If the level of oxidative stress is inadequate to cause apoptosis then it leads to cell dormancy which may revive post chemotherapy. This hypothesis aims to put forward a combinatorial approach that includes utilizing a cost effective, biocompatible and environmentally benign nanoparticulate carrier made up of lignin, loaded with anti-cancer agent and P-gp modulator, and functionalized with ligand for CD44 receptors that are over expressed on cancer cells. Antioxidant effect of lignin will overcome dormancy of cancer cells making it possible for cell cycle specific drugs to kill them and prevent relapse and active targeting will prevent untoward effects on normal cells. Thus a robust and wholesome formulation can be developed to combat colon cancer.

Melanoma treatment: from conventional to nanotechnology.

INTRODUCTION: Melanoma is the most serious form of skin cancer causing most of the skin cancer-related deaths. The incidence of melanoma has risen so dramatically over past few years that no other solid or blood malignancy comes close to it in terms of increased incidence. The main problem associated with the treatment of melanoma is low response rate to the existing treatment modalities, which in turn is due to the incomplete response by chemotherapeutic agents and inherent resistance of melanoma cells. MATERIALS AND METHODS: Conventional therapeutic strategies, as well as, recent literature on melanoma have been thoroughly studied. This review summarizes the base of anti-melanoma treatment with conventional chemotherapeutic drugs, followed by an account of recent studies which explored the potential of nanotechnology and newer strategies and agents in melanoma treatment. CONCLUSION: Although melanoma is curable if detected in its early localized form, metastatic melanoma continues to be a therapeutic challenge. Metastatic melanoma has a very poor prognosis and conventional therapies have not improved the outcomes of the treatment so far. For this reason, newer combinations of anti-melanoma drugs and newer strategies utilizing nanotechnology have been constantly explored.

Functionalized nanoliposomes loaded with anti survivin and anti angiogenic agents to enhance the activity of chemotherapy against melanoma by 4-pronged action.

Melanoma is one of the most aggressive cancers which has very low response rate and survival rate. Melanoma cells are known to be inherently resistant to the chemotherapy which results in poor outcomes and even failure of the therapy. For this reason, a better understanding of underlying mechanism of melanoma pathogenesis and resistance is required, so that more efficient and novel therapeutic strategies can be developed. Survivin is a protein which is overexpressed in melanoma cells and is known to impart resistance to them against apoptosis. Also, melanoma cells overexpress Vascular Endothelial Growth Factor (VEGF) and basic Fibroblast Growth Factor (bFGF) angiogenic growth factors which lead to aggressive angiogenesis in melanoma cells thereby making the treatment more challenging. This hypothesis presents a combinatorial approach against melanoma where an anti-survivin agent and an anti-angiogenic agent are combined with a chemotherapeutic drug and loaded in surface functionalized liposomes in order to target specific mechanisms of melanoma, thus overcoming its resistance. Thus, the study aims to overcome the resistance of melanoma cells by developing a wise combination of drugs and achieve a higher response rate in resistant melanoma model, which is usually not achieved with the existing treatment modalities.

Changing Face of Wood Science in Modern Era: Contribution of Nanotechnology.

BACKGROUND: Wood science and nanomaterials science interact together in two different aspects; a) fabrication of lignocellulosic nanomaterials derived from wood and plant-based sources and b) surface or bulk wood modification by nanoparticles. In this review, we attempt to visualize the impact of nanoparticles on the wood coating and preservation treatments based on a thorough registration of the patent databases. METHOD: The study was carried out as an overview of the scientifically most followed trends on nanoparticles utilization in wood science and wood protection depicted by recent universal filed patents. This review is exclusively targeted on the solid (timber) wood as a subject material. RESULTS: Utilization of mainly metal nanoparticles as photoprotection, antibacterial, antifungal, antiabrasive and functional component on wood modification treatments was found to be widely patented. Additionally, an apparent minimization in the emission of volatile organic compounds (VOCs) has been succeeded. CONCLUSION: Bulk wood preservation and more importantly, wood coating, splay the range of strengthening wood dimensional stability and biological degradation, against moisture absorption and fungi respectively. Nanoparticle materials have addressed various issues of wood science in a more efficient and environmental way than the traditional methods. Nevertheless, abundant tests and regulations are still needed before industrializing or recycling these products.

Microbial taxonomy in the era of OMICS: application of DNA sequences, computational tools and techniques.

The current prokaryotic taxonomy classifies phenotypically and genotypically diverse microorganisms using a polyphasic approach. With advances in the next-generation sequencing technologies and computational tools for analysis of genomes, the traditional polyphasic method is complemented with genomic data to delineate and classify bacterial genera and species as an alternative to cumbersome and error-prone laboratory tests. This review discusses the applications of sequence-based tools and techniques for bacterial classification and provides a scheme for more robust and reproducible bacterial classification based on genomic data. The present review highlights promising tools and techniques such as ortho-Average Nucleotide Identity, Genome to Genome Distance Calculator and Multi Locus Sequence Analysis, which can be validly employed for characterizing novel microorganisms and assessing phylogenetic relationships. In addition, the review discusses the possibility of employing metagenomic data to assess the phylogenetic associations of uncultured microorganisms. Through this article, we present a review of genomic approaches that can be included in the scheme of taxonomy of bacteria and archaea based on computational and in silico advances to boost the credibility of taxonomic classification in this genomic era.

Zinc oxide nanoparticles: a promising nanomaterial for biomedical applications.

Zinc oxide (ZnO) nanoparticles (NPs) are a promising platform for use in biomedical research, especially given their anticancer and antimicrobial activities. These activities are associated with the ability of ZnO NPs to generate reactive oxygen species (ROS) and induce apoptosis. In addition, ZnO NPs have been successfully exploited as drug carriers for loading and transporting drugs to target sites, thereby reducing unwanted toxicity and off-target effects, and resulting in amplified synergistic effects. Here, we discuss the synthesis and biomedical applications of ZnO NPs.

Complete Genome Analysis of Thermus parvatiensis and Comparative Genomics of Thermus spp. Provide Insights into Genetic Variability and Evolution of Natural Competence as Strategic Survival Attributes.

Thermophilic environments represent an interesting niche. Among thermophiles, the genus Thermus is among the most studied genera. In this study, we have sequenced the genome of Thermus parvatiensis strain RL, a thermophile isolated from Himalayan hot water springs (temperature >96°C) using PacBio RSII SMRT technique. The small genome (2.01 Mbp) comprises a chromosome (1.87 Mbp) and a plasmid (143 Kbp), designated in this study as pTP143. Annotation revealed a high number of repair genes, a squeezed genome but containing highly plastic plasmid with transposases, integrases, mobile elements and hypothetical proteins (44%). We performed a comparative genomic study of the group Thermus with an aim of analysing the phylogenetic relatedness as well as niche specific attributes prevalent among the group. We compared the reference genome RL with 16 Thermus genomes to assess their phylogenetic relationships based on 16S rRNA gene sequences, average nucleotide identity (ANI), conserved marker genes (31 and 400), pan genome and tetranucleotide frequency. The core genome of the analyzed genomes contained 1,177 core genes and many singleton genes were detected in individual genomes, reflecting a conserved core but adaptive pan repertoire. We demonstrated the presence of metagenomic islands (chromosome:5, plasmid:5) by recruiting raw metagenomic data (from the same niche) against the genomic replicons of T. parvatiensis. We also dissected the CRISPR loci wide all genomes and found widespread presence of this system across Thermus genomes. Additionally, we performed a comparative analysis of competence loci wide Thermus genomes and found evidence for recent horizontal acquisition of the locus and continued dispersal among members reflecting that natural competence is a beneficial survival trait among Thermus members and its acquisition depicts unending evolution in order to accomplish optimal fitness.

Cellulose nanofiber aerogel as a promising biomaterial for customized oral drug delivery.

Cellulose nanofiber (CNF) aerogels with favorable floatability and mucoadhesive properties prepared by the freeze-drying method have been introduced as new possible carriers for oral controlled drug delivery system. Bendamustine hydrochloride is considered as the model drug. Drug loading was carried out by the physical adsorption method, and optimization of drug-loaded formulation was done using central composite design. A very lightweight-aerogel-with-matrix system was produced with drug loading of 18.98%±1.57%. The produced aerogel was characterized for morphology, tensile strength, swelling tendency in media with different pH values, floating behavior, mucoadhesive detachment force and drug release profiles under different pH conditions. The results showed that the type of matrix was porous and woven with excellent mechanical properties. The drug release was assessed by dialysis, which was fitted with suitable mathematical models. Approximately 69.205%±2.5% of the drug was released in 24 hours in medium of pH 1.2, whereas ~78%±2.28% of drug was released in medium of pH 7.4, with floating behavior for ~7.5 hours. The results of in vivo study showed a 3.25-fold increase in bioavailability. Thus, we concluded that CNF aerogels offer a great possibility for a gastroretentive drug delivery system with improved bioavailability.