A review on the impact of TRAIL on cancer signaling and targeting via phytochemicals for possible cancer therapy.

Anticancer therapies have been the continual pursuit of this age. Cancer has been ravaging all across the globe breathing not just threats but demonstrating them. Remedies for cancer have been frantically sought after. Few have worked out, yet till date, the available cancer therapies have not delivered a holistic solution. In a world where the search for therapies is levitating towards natural remedies, solutions based on phytochemicals are highly prospective attractions. A lot has been achieved with inputs from plant resources, providing numerous natural remedies. In the current review, we intensely survey the progress achieved in the treatment of cancer through phytochemicals-based programmed cell death of cancer cells. More specifically, we have further reviewed and discussed the role of phytochemicals in activating apoptosis via Tumor Necrosis Factor-Alpha-Related Apoptosis-Inducing Ligand (TRAIL), which is a cell protein that can attach to certain molecules in cancer cells, killing cancer cells. The objective of this review is to enlist the various phytochemicals that are available for specifically contributing towards triggering the TRAIL cell protein-mediated cancer therapy and to point out the research gaps that require future research motivation. This is the first review of this kind in this research direction.

A Comprehensive Survey on the Expediated Anti-COVID-19 Options Enabled by Metal Complexes-Tasks and Trials.

Contemporary pharmacology dating back to the late 19th/early 20th centuries has benefitted largely from the incorporation of metal complexes. Various biological attributes have been successfully realized using metal/metal complex-based drugs. Among anticancer, antimicrobial, and antiviral applications, anticancer applications have extracted the maximum benefit from the metal complex, Cisplatin. The following review has compiled the various antiviral benefits harnessed through inputs from metal complexes. As a result of exploiting the pharmacological aspects of metal complexes, the anti-COVID-19 deliverables have been summarized. The challenges ahead, the gaps in this research area, the need to improvise incorporating nanoaspects in metal complexes, and the need to test metal complex-based drugs in clinical trials have been discussed and deliberated. The pandemic shook the entire world and claimed quite a percentage of the global population. Metal complex-based drugs are already established for their antiviral property with respect to enveloped viruses and extrapolating them for COVID-19 can be an effective way to manipulate drug resistance and mutant issues that the current anti-COVID-19 drugs are facing.

Anticancer Therapeutic Effects of Green Tea Catechins (GTCs) When Integrated with Antioxidant Natural Components.

After decades of research and development concerning cancer treatment, cancer is still at large and very much a threat to the global human population. Cancer remedies have been sought from all possible directions, including chemicals, irradiation, nanomaterials, natural compounds, and the like. In this current review, we surveyed the milestones achieved by green tea catechins and what has been accomplished in cancer therapy. Specifically, we have assessed the synergistic anticarcinogenic effects when green tea catechins (GTCs) are combined with other antioxidant-rich natural compounds. Living in an age of inadequacies, combinatorial approaches are gaining momentum, and GTCs have progressed much, yet there are insufficiencies that can be improvised when combined with natural antioxidant compounds. This review highlights that there are not many reports in this specific area and encourages and recommends research attention in this direction. The antioxidant/prooxidant mechanisms of GTCs have also been highlighted. The current scenario and the future of such combinatorial approaches have been addressed, and the lacunae in this aspect have been discussed.

Mushroom Polysaccharide-Assisted Anticarcinogenic Mycotherapy: Reviewing Its Clinical Trials.

Of the biologically active components, polysaccharides play a crucial role of high medical and pharmaceutical significance. Mushrooms have existed for a long time, dating back to the time of the Ancient Egypt and continue to be well explored globally and experimented with in research as well as in national and international cuisines. Mushroom polysaccharides have slowly become valuable sources of nutraceuticals which have been able to treat various diseases and disorders in humans. The application of mushroom polysaccharides for anticancer mycotherapy is what is being reviewed herein. The widespread health benefits of mushroom polysaccharides have been highlighted and the significant inputs of mushroom-based polysaccharides in anticancer clinical trials have been presented. The challenges and limitation of mushroom polysaccharides into this application and the gaps in the current application areas that could be the future direction have been discussed.

Evaluating the Anticarcinogenic Activity of Surface Modified/Functionalized Nanochitosan: The Emerging Trends and Endeavors.

Chitosan begins its humble journey from marine food shell wastes and ends up as a versatile nutraceutical. This review focuses on briefly discussing the antioxidant activity of chitosan and retrospecting the accomplishments of chitosan nanoparticles as an anticarcinogen. The various modified/functionalized/encapsulated chitosan nanoparticles and nanoforms have been listed and their biomedical deliverables presented. The anticancer accomplishments of chitosan and its modified composites have been reviewed and presented. The future of surface modified chitosan and the lacunae in the current research focus have been discussed as future perspective. This review puts forth the urge to expand the scientific curiosity towards attempting a variety of functionalization and surface modifications to chitosan. There are few well known modifications and functionalization that benefit biomedical applications that have been proven for other systems. Being a biodegradable, biocompatible polymer, chitosan-based nanomaterials are an attractive option for medical applications. Therefore, maximizing expansion of its bioactive properties are explored. The need for applying the ideal functionalization that will significantly promote the anticancer contributions of chitosan nanomaterials has also been stressed.

Nanochitosan: Commemorating the Metamorphosis of an ExoSkeletal Waste to a Versatile Nutraceutical.

Chitin (poly-N-acetyl-D-glucosamine) is the second (after cellulose) most abundant organic polymer. In its deacetylated form-chitosan-becomes a very interesting material for medical use. The chitosan nano-structures whose preparation is described in this article shows unique biomedical value. The preparation of nanochitosan, as well as the most vital biomedical applications (antitumor, drug delivery and other medical uses), have been discussed in this review. The challenges confronting the progress of nanochitosan from benchtop to bedside clinical settings have been evaluated. The need for inclusion of nano aspects into chitosan research, with improvisation from nanotechnological inputs has been prescribed for breaking down the limitations. Future perspectives of nanochitosan and the challenges facing nanochitosan applications and the areas needing research focus have been highlighted.

Insights into Bioinformatic Applications for Glycosylation: Instigating an Awakening towards Applying Glycoinformatic Resources for Cancer Diagnosis and Therapy.

Glycosylation plays a crucial role in various diseases and their etiology. This has led to a clear understanding on the functions of carbohydrates in cell communication, which eventually will result in novel therapeutic approaches for treatment of various disease. Glycomics has now become one among the top ten technologies that will change the future. The direct implication of glycosylation as a hallmark of cancer and for cancer therapy is well established. As in proteomics, where bioinformatics tools have led to revolutionary achievements, bioinformatics resources for glycosylation have improved its practical implication. Bioinformatics tools, algorithms and databases are a mandatory requirement to manage and successfully analyze large amount of glycobiological data generated from glycosylation studies. This review consolidates all the available tools and their applications in glycosylation research. The achievements made through the use of bioinformatics into glycosylation studies are also presented. The importance of glycosylation in cancer diagnosis and therapy is discussed and the gap in the application of widely available glyco-informatic tools for cancer research is highlighted. This review is expected to bring an awakening amongst glyco-informaticians as well as cancer biologists to bridge this gap, to exploit the available glyco-informatic tools for cancer.

The MUDENG Augmentation: A Genesis in Anti-Cancer Therapy?

Despite multitudes of reports on cancer remedies available, we are far from being able to declare that we have arrived at that defining anti-cancer therapy. In recent decades, researchers have been looking into the possibility of enhancing cell death-related signaling pathways in cancer cells using pro-apoptotic proteins. Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL) and Mu-2/AP1M2 domain containing, death-inducing (MUDENG, MuD) have been established for their ability to bring about cell death specifically in cancer cells. Targeted cell death is a very attractive term when it comes to cancer, since most therapies also affect normal cells. In this direction TRAIL has made noteworthy progress. This review briefly sums up what has been done using TRAIL in cancer therapeutics. The importance of MuD and what has been achieved thus far through MuD and the need to widen and concentrate on applicational aspects of MuD has been highlighted. This has been suggested as the future perspective of MuD towards prospective progress in cancer research.

Cytotoxic and apoptotic potential of Phyllodium elegans extracts on human cancer cell lines.

The extract of Phyllodium (P.) elegans was investigated for its anti-cancer properties on brain astroglioma cells (U251-MG), colorectal carcinoma cells (HCT116), and malignant melanoma cells (A375). P. elegans methanolic extract (PeME) showed cytotoxicity on all three cancer cell lines tested. The cell viability assay revealed that PeME significantly reduced the viability of these cells. Clear apoptotic features such as cellular morphology, cell shrinkage, and augmentation of dead cells were observed. Flow cytometry and fluorescence staining techniques confirmed the apoptotic property of PeME. In vitro scratch invasion assay showed that cell migration rate was significantly reduced. Fluorescence microscopic studies using 4',6-diamidino-2-phenylindole staining showed early and late signs of apoptosis after PeME treatment. Upon PeME stimulation, activation of caspase-3/-9 and Mu-2-related death-inducing gene (MUDENG, MuD) was observed by western blot analysis. JC-1 staining analysis by flow cytometry showed that PeME depolarized the mitochondria membrane potential (MMP). Collectively, these findings, for the first time, point to the fact that PeME has anti-cancer properties against brain, colon, and skin cancer cell lines by depolarizing the MMP and activating apoptotic signaling through the activation of caspase-3/-9 as well as MuD. This is the first report reporting the anticancer activity of this specific plant extract.[Figure: see text].

The graviola impact on human astroglioma cells: functional significance of MUDENG.

Graviola (Annona muricate) is a coveted tropical plant that has been found to be effective against many human cancers. Malignant glioblastoma multiformes are the most common and aggressive malignant forms of astrocytoma in the central nervous system. MUDENG (Mu-2-related death-inducing gene, MuD) is involved in cell death signaling. In this study, we investigated the impact of extracts from graviola leaves (from Korea and Africa), fruits and seeds against human astroglioma cells. Interestingly, graviola leaf extract-Korea (GLE-K), graviola leaf extract-Africa (GLE-A) and graviola fruit extract-Africa (GFE-A) exhibited significant cytotoxic effects on the cell proliferation in a dose-dependent manner and altered the MuD expression pattern. Cell cycle analyses revealed that GLE-A and GLE-K triggered no significant induction of apoptosis at concentrations up to 5% in U251-MG cells, while in GLE-K treated cells at 10% concentrations, there were much fewer apoptotic cells (33.64%) compared to those in GLE-A (73.55%) treated cells. In the case of GFE-A treated cells, 5% graviola extract (GE) concentration resulted in predominant cells entering the apoptotic phase (59.31%), whereas almost no significant increase in apoptotic cells was observed in GSE-A treated cells (1.38%) even up to 25% of graviola extract (GE) concentration. While using stable transfectants knock-out (KO)(-)-and overexpressing (OE)-MuD(+), significant and consistent differences in the cell viability (enhanced anti-astroglioma effect of GEs) were observed in KO-MuD(-) cells. This validated the functional consequence of MuD in the anti-astroglioma activity of GEs. Our results confirmed that GFE-A possesses the highest anti-astroglioma activity followed by the leaf extracts (GLE-A/K). This is the first report that highlights the MuD aspect of GEs.

Silver nanoparticle-induced hormesis of astroglioma cells: A Mu-2-related death-inducing protein-orchestrated modus operandi.

Hormesis is a dose-response phenomenon that, when applied to nanomaterial-biological interactions, refers to growth stimulation at low doses and growth inhibition at high doses. MUDENG (Mu-2-related death-inducing gene, MuD) is involved in cell death signaling. Astrocytes, the major glial cell type in the central nervous system, are a major source of brain tumors. In this study, we investigated whether silver nanoparticles (AgNPs) induce hormesis in astroglioma cells and the possible involvement of MuD in AgNP-induced hormesis. AgNPs exhibited cytotoxic effects on cell proliferation in a dose-dependent manner and increased MuD expression was observed during AgNP-induced astroglioma hormesis. Studies using MuD-knockout cells and MuD siRNA transfection showed that MuD might influence cell viability upon AgNP treatment. In addition, apoptotic cell population and production of reactive oxygen species in the absence of MuD were significantly increased. The phosphorylation of two mitogen-activated protein kinases, p38 and extracellular signal-regulated kinase (ERK), but not c-Jun N-terminal kinases (JNK), was observed upon AgNP stimulation. In summary, AgNPs at low doses induced hormesis of human astroglioma cells, and MuD and p38/ERK mediators are involved in AgNP-induced astroglioma hormesis, resulting in beneficial effects from the cellular point of view.

The unequivocal preponderance of biocomputation in clinical virology.

Bioinformatics and computer based data simulation and modeling are captivating biological research, delivering great results already and promising to deliver more. As biological research is a complex, intricate, diverse field, any available support is gladly taken. With recent outbreaks and epidemics, pathogens are a constant threat to the global economy and security. Virus related plagues are somehow the most difficult to handle. Biocomputation has provided appreciable help in resolving clinical virology related issues. This review, for the first time, surveys the current status of the role of computation in virus related research. Advances made in the fields of clinical virology, antiviral drug design, viral immunology and viral oncology, through input from biocomputation, have been discussed. The amount of progress made and the software platforms available are consolidated in this review. The limitations of computation based methods are presented. Finally, the challenges facing the future of biocomputation in clinical virology are speculated upon.

Nature nominee quercetin's anti-influenza combat strategy-Demonstrations and remonstrations.

Nature's providences are rather the choicest remedies for human health and welfare. One such is quercetin, which is nature's nominee for cancer cure and recently demonstrated against influenza attack. Quercetin is highly recognized for its anticancer applications. This review emphasizes on yet another gift that this compound has to offer for mankind, which is none other than combating the deadly evasive influenza virus. The chemistry of this natural bioflavonoid and its derivatives and its modus operandi against influenza virus is consolidated into this review. The advancements and achievements made in the anti-influenza clinical history are also documented. Further, the challenges facing the progress of this compound to emerge as a predominant anti-influenza drug are discussed, and the future perspective for breaking its limitations through integration with nanoplatforms is envisioned.

The ethanopharmacological aspect of carbon nanodots in turmeric smoke.

Smoke manifested ever since our ancient's lit fire; today it has evolved to become an environmental concern. However, medicinal smoke is still part of man's natural remedies, religious and cultural practices too. The Asiatic household practice of burning turmeric rhizomes to relieve nose and chest congestion is a well known yet never scientifically authenticated or studied practice. For the first time we investigate the components of these turmeric smudges, validate their antimicrobial and anticancer properties and their cell compatibility. With smoke there is always nanoparticulate carbon and turmeric smoke is no exception. If so, what is the role of the nano carbon (NC) in the turmeric smudge effect? This study isolated, characterized and exposed these secret natural NC undercover agents in turmeric smoke. Their unequivocal role in the ethanopharmocological activity of turmeric smudging has been demonstrated. This work opens a new avenue for use of such nano components of smoke for harnessing the ethanopharmacological property of various medicinal smokes, by excluding the smoke factor, through extracting the nano carbon material in them. This is a possibility to realizing the use of such naturally available nanomaterial, as an eco friendly substitute for the notorious anthropogenic nanomaterials.

A nano-patterned self assembled monolayer (SAM) rutile titania cancer chip for rapid, low cost, highly sensitive, direct cancer analysis in MALDI-MS.

We developed a cancer chip by nano-patterning a highly sensitive SAM titanium surface capable of capturing and sensing concentrations as low as 10 cancer cells/mL from the environment by Matrix Assisted Laser Desorption and Ionization Time of Flight Mass Spectrometry (MALDI-TOF MS). The current approach evades any form of pretreatment and sample preparation processes; it is time saving and does not require the (expensive) conventional MALDI target plate. The home made aluminium (Al) target holder cost, on which we loaded the cancer chips for MALDI-TOF MS analysis, is about 60 USD. While the conventional stainless steel MALDI target plate is more than 700 USD. The SAM surface was an effective platform leading to on-chip direct MALDI-MS detection of cancer cells. We compared the functionality of this chip with the unmodified titanium surfaces and thermally oxidized (TO) titanium surfaces. The lowest detectable concentration of the TO chip was 10(3) cells/mL, while the lowest detectable concentration of the control or unmodified titanium chips was 10(6) cells/mL. Compared to the control surface, the SAM cancer chip showed 100,000 times of enhanced sensitivity and compared with the TO chip, 1000 times of increased sensitivity. The high sensitivity of the SAM surfaces is attributed to the presence of the rutile SAM, surface roughness and surface wettability as confirmed by AFM, XRD, contact angle microscope and FE-SEM. This study opens a new avenue for the potent application of the SAM cancer chip for direct cancer diagnosis by MALDI-TOF MS in the near future.

Quantum dot applications endowing novelty to analytical proteomics.

This review surveys all the state-of-art applications of quantum dots (QDs) in conventional and modern analytical methods in proteomic studies. A brief introduction of QDs and their properties is initially presented followed by outlining the application of QDs in fluorescence, MS, imaging, and cancer-based proteomics. The in-depth application of QDs in MALDI-MS and surface assisted laser desorption/ionization-MS has been elaborately discussed, summarizing the speculated mechanism behind the protein-QDs interactions during QD matrix applications leading to enhanced detection sensitivity.

Rapid, sensitive and direct analysis of exopolysaccharides from biofilm on aluminum surfaces exposed to sea water using MALDI-TOF MS.

Biofilm studies have extensive significance since their results can provide insights into the behavior of bacteria on material surfaces when exposed to natural water. This is the first attempt of using matrix-assisted laser desorption/ionization-mass spectrometry (MALDI-MS) for detecting the polysaccharides formed in a complex biofilm consisting of a mixed consortium of marine microbes. MALDI-MS has been applied to directly analyze exopolysaccharides (EPS) in the biofilm formed on aluminum surfaces exposed to seawater. The optimal conditions for MALDI-MS applied to EPS analysis of biofilm have been described. In addition, microbiologically influenced corrosion of aluminum exposed to sea water by a marine fungus was also observed and the fungus identity established using MALDI-MS analysis of EPS. Rapid, sensitive and direct MALDI-MS analysis on biofilm would dramatically speed up and provide new insights into biofilm studies due to its excellent advantages such as simplicity, high sensitivity, high selectivity and high speed. This study introduces a novel, fast, sensitive and selective platform for biofilm study from natural water without the need of tedious culturing steps or complicated sample pretreatment procedures.

TiO2 nanoparticle assisted mass spectrometry as biosensor of Staphylococcus aureus, key pathogen in nosocomial infections from air, skin surface and human nasal passage.

For the first time, we have demonstrated the use of mass spectrometry as a biosensor for detecting a clinically important bacterium: Staphylococcus aureus in air, nasal passage and skin samples using culture-free, rapid, direct analysis via TiO(2) nanoparticles (NPs) assisted MALDI-MS. When this bacterium is predominating, the nasal passage of an individual is observed to lead to wound infections especially when the individual has a surgery or some wounds. This study indicates that even at very low concentrations of an individual bacterium can be directly detected from a mixture of bacteria using the MALDI-MS analysis without the requirement of any culturing steps or any other sample pretreatment techniques. The current approach is extremely simple, rapid, straightforward and sensitive which could be widely applied for the detection of this deadly pathogen in clinical as well as environmental samples.