Cancer is one of the deadliest diseases and poses a risk to people all over the world. Surgery, chemo, and radiation therapy have been the only options available until today to combat this major ...problem. Chemotherapeutic drugs have been used for treatment for more than 50 years. Unfortunately, these drugs have inherent cytotoxicities and tumor cells have started inducing resistance against these drugs. Other common techniques such as surgery and radiotherapy have their own drawbacks. Therefore, such techniques are incompetent tools to alleviate the disease efficiently without any adverse effects. This scenario has inspired researchers to develop alternative techniques with enhanced therapeutic effects and minimal side effects. Such techniques include targeted therapy, liposomal therapy, hormonal therapy, and immunotherapy, etc. However, these therapies are expensive and not effective enough. Furthermore, researchers have conjugated therapeutic agents or drugs with different molecules, delivery vectors, and/or imaging modalities to combat such problems and enhance the therapeutic effect. This conjugation technique has led to the development of bioconjugation therapy, in which at least one molecule is of biological origin. These bioconjugates are the new therapeutic strategies, having prospective synergistic antitumor effects and have potency to overcome the complications being produced by chemo drugs. Herein, we provide an overview of various bioconjugates developed so far, as well as their classification, characteristics, and targeting approach for cancer. Additionally, the most popular nanostructures based on their organic or inorganic origin (metallic, magnetic, polymeric nanoparticles, dendrimers, and silica nanoparticles) characterized as nanocarriers are also discussed. Moreover, we hope that this review will provide inspiration for researchers to develop better bioconjugates as therapeutic agents.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Curcumin, very rightly referred to as "a wonder drug" is proven to be efficacious in a variety of inflammatory disorders including cancers. Antiaging, anti-inflammatory, antioxidant, antitumor, ...chemosensitizing, P-gp efflux inhibiting, and antiproliferative activity are some of the striking features of curcumin, highlighting its importance in chemotherapy. Curcumin inhibits Bcl-2, Bcl-XL, VEGF, c-My
, ICAM-1, EGFR, STAT3 phosphorylation, and cyclin D1 genes involved in the various stages of breast, prostate, and gastric cancer proliferation, angiogenesis, invasion, and metastasis. The full therapeutic potential of curcumin however remains under explored mainly due to poor absorption, rapid metabolism and systemic elimination culminating in its poor bioavailability. Furthermore, curcumin is insoluble, unstable at various pH and is also prone to undergo photodegradation. Nanotechnology can help improve the therapeutic potential of drug molecules with compromised biopharmaceutical profiles. Solid lipid nanoparticles (SLNs) are the latest offshoot of nanomedicine with proven advantages of high drug payload, longer shelf life, biocompatibility and biodegradability, and industrial amenability of the production process. We successfully developed CLEN (Curcumin encapsulated lipidic nanoconstructs) containing 15 mg curcumin per ml of the SLN dispersion with highest (till date, to our knowledge) increase in solubility of curcumin in an aqueous system by 1.4 × 10
times as compared to its intrinsic solubility of 11 ng/ml and high drug loading (15% w/v with respect to lipid matrix). Zero-order release kinetics observed for CLEN versus first order release for free curcumin establish controlled release nature of the developed CLEN. It showed 69.78 times higher oral bioavailability with respect to free curcumin; 9.00 times higher than a bioavailable marketed formulation (CurcuWIN
). The formulation showed 104, 13.3, and 10-times enhanced stability at pH 6.8, 1.2, and 7.4, respectively. All these factors ensure the efficacy of CLEN in treating cancer and other inflammatory diseases.
Hadoop‐based analytic framework for cyber forensics Chhabra, Gurpal Singh; Singh, Varinderpal; Singh, Maninder
International journal of communication systems,
October 2018, 2018-10-00, 20181001, Volume:
31, Issue:
15
Journal Article
Peer reviewed
Summary
With an exponential increase in the data size and complexity of various documents to be investigated, existing methods of network forensics are found not much efficient with respect to ...accuracy and detection ratio. The existing techniques for network forensic analysis exhibit inherent limitations while processing a huge volume, variety, and velocity of data. It makes network forensic a time‐consuming and resource‐consuming task. To balance time taken and output delivered, these existing techniques put a limit on the amount of data under analysis, which results in a polynomial time complexity of these solutions. So to mitigate these issues, in this paper, we propose an effective framework to overcome the limitation to handle large volume, variety, and velocity of data. An architectural setup that consists of MapReduce framework on top of Hadoop Distributed File System environment is proposed in this paper. The proposed framework demonstrates its capability to handle issues of storage and processing of big data using cloud computing. Also, in the proposed framework, supervised machine learning (random forest‐based decision tree) algorithm has been implemented to demonstrate better sensitivity. To train and validate the model, online available data set from CAIDA is taken and university network traffic samples, with increasing size, has been taken for experiment. Results thus obtained confirm the superiority of the proposed framework in network forensics, with an average accuracy of 99.34% (malicious and nonmalicious traffic).
Handling and securing high velocity with a large bulk of traffic flowing is the biggest challenge. Research work proposes to handle cyber traffic security, with 99.34% accuracy, with the scalability of the framework to cope up with exponentially increasing traffic per second on the network. MapReduce framework that works in Hadoop Distributed File System has been proposed and validated with standard supervised machine learning algorithm.
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BFBNIB, FZAB, GIS, IJS, IZUM, KILJ, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBMB, UL, UM, UPUK
Developing an innovative protective structure with excellent energy absorption performance is a continuous research effort. The emerging additive manufacturing techniques allow fabricating structures ...with complex geometrical shapes which have the potential to yield unprecedented energy absorption properties.
Accordingly, in this paper, the crush and energy absorption behaviour of new designs, namely Concave Tubes (CTs) featuring inwardly curved sidewalls, is assessed experimentally and compared to that of Standard tubes (STs) featuring straight sidewalls. Tubes with different geometrical configurations, including concave circular (CC), concave square (CS), standard circular (SC), and standard square (SS), are fabricated using the Selective Laser Melting (SLM) process from AlSi10Mg aluminium powder and then crushed axially under quasi-static loading. It was found that the tubes have fractured and developed a splitting deformation mode, instead of progressive buckling, during the axial crushing resulting in relatively low energy absorption performance. The experimental results revealed superior energy absorption performance for the CTs over the STs. A Multi-Attribute Decision Making (MADM) technique known as Complex Proportional Assessment (COPRAS) is used to identify the best design. The COPRAS results show that the CC design is the best energy absorbing tube outperforming all other configurations presented in this paper.
•Innovative concave tubes with circular and square cross-sections were crushed axially.•SLM process was utilized to fabricate the tubes.•Energy absorption responses of the concave tubes were determined and compared with the standard tubes.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract
The electronic structure and transport properties of GaN-MoS
2
heterostructure have been theoretically investigated using first principles calculations. Among the various possibilities of ...stacking MoS
2
over GaN monolayers to form heterostructure, we studied the case in which the S atom is directly placed over the Ga atom. This type of stacking is energetically favourable. The GaN-MoS
2
heterostructure preserves the direct band gap nature of MoS
2
monolayer i.e. it has direct band gap of 0.97 eV. The valence bands and conduction bands adjoining the fermi level are mostly contributed by N and Mo atoms. To study the performance of both n-type and p-type GaN-MoS
2
heterostructure in thermoelectric applications, we investigate the transport coefficients on which the ZT parameter depends. We found that p-type heterostructure has high electrical conductivity as compared to n-type heterostructure. Due to which it has a high magnitude of power factor which is one of the deciding factors in the evaluation of ZT parameter.
The havoc unleashed by COVID-19 pandemic has paved way for secondary ominous fungal infections like Mucormycosis. It is caused by a class of opportunistic pathogens from the order Mucorales. Fatality ...rates due to this contagious infection are extremely high. Numerous clinical manifestations result in damage to multiple organs subject to the patient's underlying condition. Lack of a proper detection method and reliable treatment has made the management of this infection troublesome. Several reports studying the behavior pattern of Mucorales inside the host by modulation of its defense mechanisms have helped in understanding the pathogenesis of this angio-invasive infection. Many recent advances in diagnosis and treatment of this fungal infection have not been much beneficial. Therefore, there is a need to foster more viable strategies. This article summarizes current and imminent approaches that could aid effective management of these secondary infections in these times of global pandemic. It is foreseen that the development of newer antifungal drugs, antimicrobial peptides, and nanotechnology-based approaches for drug delivery would help combat this infection and curb its spread.
The integrity of the blood-brain barrier (BBB) is essential for normal central nervous system (CNS) functioning. Considering the significance of BBB in maintaining homeostasis and the neural ...environment, we aim to provide an overview of significant aspects of BBB. Worldwide, the treatment of neurological diseases caused by BBB disruption has been a major challenge. BBB also restricts entry of neuro-therapeutic drugs and hinders treatment modalities. Hence, currently nanotechnology-based approaches are being explored on large scale as alternatives to conventional methodologies. It is necessary to investigate the in-depth characteristic features of BBB to facilitate the discovery of novel drugs that can successfully cross the barrier and target the disease effectively. It is imperative to discover novel strategies to treat life-threatening CNS diseases in humans. Therefore, insights regarding building blocks of BBB, activation of immune response on breach of this barrier, and various autoimmune neurological disorders caused due to BBB dysfunction are discussed. Further, special emphasis is given on delineating BBB disruption leading to CNS disorders. Moreover, various mechanisms of transport pathways across BBB, several novel strategies, and alternative routes by which drugs can be properly delivered into CNS are also discussed.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
The current piece of research intends to evaluate the potential of combining etodolac with deformable-emulsomes, a flexible vesicular system, as a promising strategy for the topical therapy of ...arthritis. The developed carrier system featured nanometric dimensions (102 nm), an improved zeta potential (- 5.05 mV), sustained drug release (31.33%), and enhanced drug deposition (33.13%) of DE-gel vis-à-vis conventional system (10.34% and 14.71%). The amount of permeation of the developed nano formulation across skin layers was demonstrated through CLSM and dermatokinetics studies. The safety profile of deformable-emulsomes has been investigated through in vitro HaCaT cell culture studies and skin compliance studies. The efficacy of the DE-gel formulation was sevenfold higher in case of Xylene induced ear edema model and 2.2-folds in CFA induced arthritis model than that of group treated with conventional gel (p < 0.01). The main technological rationale lies in the use of phospholipid and sodium deoxycholate-based nanoscale flexible lipoidal vesicles, which effectively encapsulate drug molecules within their interiors. This encapsulation enhances the molecular interactions and facilitates the transportation of the drug molecule effectively to the target-site. Hence, these findings offer robust scientific evidence to support additional investigation into the potential utility of flexible vesicular systems as a promising drug delivery alternative for molecules of this nature.
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IZUM, KILJ, NUK, PILJ, PNG, SAZU, UL, UM, UPUK
Bacterial contamination of water and food is a grave health concern rendering humans quite vulnerable to disease(s), and proving, at times, fatal too. Exploration of the novel diagnostic tools is, ...accordingly, highly called for to ensure rapid detection of the pathogenic bacteria, particularly Escherichia coli. The current manuscript, accordingly, reports the use of silane-functionalized glass matrices and antibody-conjugated cadmium telluride (CdTe) quantum dots (QDs) for efficient detection of E. coli. Synthesis of QDs (size: 5.4-6.8 nm) using mercaptopropionic acid (MPA) stabilizer yielded stable photoluminescence (∼62%), corroborating superior fluorescent characteristics. A test sample, when added to antibody-conjugated matrices, followed by antibody-conjugated CdTe-MPA QDs, formed a pathogen-antibody QDs complex. The latter, during confocal microscopy, demonstrated rapid detection of the selectively captured pathogenic bacteria (10 microorganism cells/10 μL) with enhanced sensitivity and specificity. The work, overall, encompasses establishment and design of an innovative detection platform in microbial diagnostics for rapid capturing of pathogens in water and food samples.
Background Coronaviruses such as Severe Acute Respiratory Syndrome coronavirus (SARS), Middle Eastern Respiratory Syndrome (MERS) and Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) are ...associated with critical illnesses, including severe respiratory disorders. SARS-CoV-2 is the causative agent of the deadly COVID-19 illness, which has spread globally as a pandemic. SARS-CoV-2 may enter the human body through olfactory lobes and interact with the angiotensin-converting enzyme2 (ACE2) receptor, further facilitating cell binding and entry into the cells. Reports have shown that the virus can pass through the blood-brain barrier (BBB) and enter the central nervous system (CNS), resulting in various disorders. Cell entry by SARS-CoV-2 largely relies on TMPRSS2 and cathepsin L, which activate S protein. TMPRSS2 is found on the cell surface of respiratory, gastrointestinal and urogenital epithelium, while cathepsin-L is a part of endosomes. Aim The current review aims to provide information on how SARS-CoV-2 infection affects brain function.. Furthermore, CNS disorders associated with SARS-CoV-2 infection, including ischemic stroke, cerebral venous thrombosis, Guillain-Barré syndrome, multiple sclerosis, meningitis, and encephalitis, are discussed. The many probable mechanisms and paths involved in developing cerebrovascular problems in COVID patients are thoroughly detailed. Main body There have been reports that the SARS-CoV-2 virus can cross the blood-brain barrier (BBB) and enter the central nervous system (CNS), where it could cause a various illnesses. Patients suffering from COVID-19 experience a range of neurological complications, including sleep disorders, viral encephalitis, headaches, dysgeusia, and cognitive impairment. The presence of SARS-CoV-2 in the cerebrospinal fluid (CSF) of COVID-19 patients has been reported. Health experts also reported its presence in cortical neurons and human brain organoids. The possible mechanism of virus infiltration into the brain can be neurotropic, direct infiltration and cytokine storm-based pathways. The olfactory lobes could also be the primary pathway for the entrance of SARS-CoV-2 into the brain. Conclusions SARS-CoV-2 can lead to neurological complications, such as cerebrovascular manifestations, motor movement complications, and cognitive decline. COVID-19 infection can result in cerebrovascular symptoms and diseases, such as strokes and thrombosis. The virus can affect the neural system, disrupt cognitive function and cause neurological disorders. To combat the epidemic, it is crucial to repurpose drugs currently in use quickly and develop novel therapeutics. Keywords: SARS-CoV-2, COVID, Blood-brain barrier, Central nervous system, Neuroinvasion, ACE-2, Cerebrovascular disease
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