Impact of anabolic androgenic steroids on COVID-19.

In the wake of the Novel Coronavirus arrival, the world witnessed the fragility of healthcare systems and the resilience of healthcare workers who stood on the front lines. SARS-CoV-2, also known as COVID-19 or severe acute respiratory syndrome, first appeared in China in December 2019. The infection quickly spread across the nation and the world. All countries severely restricted social interaction to stop the virus's transmission, impacting all sporting, social, and recreational activities. Anabolic androgenic steroids (AASs) are frequently used illegally to enhance strength and physical attractiveness. However, they could hurt immune system health. Much research hasn't been done yet on the connection between Covid-19 and AASs. Synthetic testosterone analogs known as anabolic androgenic steroids (AASs) can have an immune-system-altering effect. Sportspeople and bodybuilders are vulnerable to AAS abuse. Governmental reactions to the coronavirus infection issue over the last year have drawn much attention and discussion regarding public services, the experience and lessons learned from different limitations, and strategies for dealing with potential future pandemics. Using AAS has the potential to cause a variety of adverse reactions, including cardiovascular issues (including high blood pressure, heart disease, and blood clots), liver damage, renal failure, mood swings, aggressiveness, and psychiatric disorders. Individuals already suffering from severe respiratory conditions like COVID-19 may have these risks increased. This review mainly highlights the anabolic androgen steroids use and its unseen effects on coronavirus patients and gymnastics.

Bioanalytical Method Development and Validation of Doxorubicin and Lapatinib in Rat Plasma Using UHPLC-HESI-LTQ-MS.

Cancer is considered a silent killer. The complexity of cancer makes it earn that title. So far there are only a few approaches to treat cancer. Among them, chemotherapy is considered the best approach. Many chemotherapeutical compounds are commercially available in the market. Among them, doxorubicin (DOX) and lapatinib (LAP) are considered blockbuster molecules. However, DOX suffers from poor bioavailability and exhibits cardiotoxicity. Interestingly, a fixed dose combination of DOX and LAP significantly decreases the cardiotoxic effect of DOX. To enhance the oral bioavailability of DOX and to avail the synergistic effect of LAP, many formulations have been made. To quantify both compounds in any formulation or biological matrix, an Liquid chromatography-Mass Spectrometry (LC-MS) method is required. In this present study, a simple and rapid Ultra High-Performance Liquid Chromatography - Heated Electron Spray Ionization - Mass Spectrometry (UHPLC-HESI-MS) bioanalytical method was developed. The developed method was validated as per the regulatory guidelines. The validated bioanalytical method had a lower limit of quantification of 0.75 ng. A simple protein precipitation technique was optimized to extract the compounds from the rat plasma. All the validation parameters were found to be within the limits as per the regulatory guidelines. A novel and rapid analytical method was successfully developed and validated. This developed method can be used to quantify the DOX and LAP in any formulation and biological matrix.

Biocompatible and optically stable hydrophobic fluorescent carbon dots for isolation and imaging of lipid rafts in model membrane.

Lateral heterogeneity in cell membranes features a variety of compositions that influence their inherent properties. One such biophysical variation is the formation of a membrane or lipid raft, which plays important roles in many cellular processes. The lipid rafts on the cell membrane are mostly identified by specific dyes and heavy metal quantum dots, which have their own drawbacks, such as cytotoxicity, photostability, and incompatibility. To this end, we synthesized special, hydrophobic, fluorescent, photostable, and non-cytotoxic carbon dots (CDs) by solvent-free thermal treatment using non-cytotoxic materials and incorporated into the lipid bilayers of giant unilamellar vesicles (GUVs) made from 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) and dipalmitoylphosphatidylcholine (DPPC) lipids. A 2:2:1 mixture of DOPC, DPPC, and cholesterol (Chol) develops lipid rafts on the membrane by phase separation. The photophysical properties of the CDs get modulated on incorporation into the lipid rafts that identifies the membrane heterogeneity. The main attempt in this work is to develop a new, simple, cost-effective, and bio-friendly lipid raft marker, which can be used in biological applications, alongside other conventional raft markers, with more advantages.

Biophysical Characterization of Pro-apoptotic BimBH3 Peptides Reveals an Unexpected Capacity for Self-Association.

Bcl-2 proteins orchestrate the mitochondrial pathway of apoptosis, pivotal for cell death. Yet, the structural details of the conformational changes of pro- and antiapoptotic proteins and their interactions remain unclear. Pulse dipolar spectroscopy (double electron-electron resonance [DEER], also known as PELDOR) in combination with spin-labeled apoptotic Bcl-2 proteins unveils conformational changes and interactions of each protein player via detection of intra- and inter-protein distances. Here, we present the synthesis and characterization of pro-apoptotic BimBH3 peptides of different lengths carrying cysteines for labeling with nitroxide or gadolinium spin probes. We show by DEER that the length of the peptides modulates their homo-interactions in the absence of other Bcl-2 proteins and solve by X-ray crystallography the structure of a BimBH3 tetramer, revealing the molecular details of the inter-peptide interactions. Finally, we prove that using orthogonal labels and three-channel DEER we can disentangle the Bim-Bim, Bcl-xL-Bcl-xL, and Bim-Bcl-xL interactions in a simplified interactome.

Novel Class of Isoxazole-Based Gelators for the Separation of Bisphenol A from Water and Cleanup of Oil Spills.

A series of low-molecular-weight gelators based on an isoxazole backbone were synthesized, which showed robust and phase-selective gelation of a series of oils. Due to their excellent phase-selective and cogelation properties, they were employed for the separation of bisphenol and the recovery of oil spills from water. The driving force and morphology of these gels were characterized by spectroscopic and microscopic studies.

Interactions between BIM Protein and Beta-Amyloid May Reveal a Crucial Missing Link between Alzheimer's Disease and Neuronal Cell Death.

Extensive neuronal cell death is among the pathological hallmarks of Alzheimer's disease. While neuron death is coincident with formation of plaques comprising the beta-amyloid (Aß) peptide, a direct causative link between Aß (or other Alzheimer's-associated proteins) and cell toxicity is yet to be found. Here we show that BIM-BH3, the primary proapoptotic domain of BIM, a key protein in varied apoptotic cascades of which elevated levels have been found in brain cells of patients afflicted with Alzheimer's disease, interacts with the 42-residue amyloid isoform Aß42. Remarkably, BIM-BH3 modulated the structure, fibrillation pathway, aggregate morphology, and membrane interactions of Aß42. In particular, BIM-BH3 inhibited Aß42 fibril-formation, while it simultaneously enhanced protofibril assembly. Furthermore, we discovered that BIM-BH3/Aß42 interactions induced cell death in a human neuroblastoma cell model. Overall, our data provide a crucial mechanistic link accounting for neuronal cell death in Alzheimer's disease patients and the participation of both BIM and Aß42 in the neurotoxicity process.

Correction: Tuneable light-emitting carbon-dot/polymer flexible films prepared through one-pot synthesis.

Correction for 'Tuneable light-emitting carbon-dot/polymer flexible films prepared through one-pot synthesis' by Susanta Kumar Bhunia, et al., Nanoscale, 2016, 8, 3400-3406.

Bacoside-A, an Indian Traditional-Medicine Substance, Inhibits ß-Amyloid Cytotoxicity, Fibrillation, and Membrane Interactions.

Bacoside-A, a family of compounds extracted from the Bacopa monniera plant, is a folk-medicinal substance believed to exhibit therapeutic properties, particularly enhancing cognitive functions and improving memory. We show that bacoside-A exerted significant inhibitory effects upon cytotoxicity, fibrillation, and particularly membrane interactions of amyloid-beta (1-42) (Aß42), the peptide playing a prominent role in Alzeheimer's disease progression and toxicity. Specifically, preincubation of bacoside-A with Aß42 significantly reduced cell toxicity and inhibited fibril formation both in buffer solution and, more significantly, in the presence of membrane vesicles. In parallel, spectroscopic and microscopic analyses reveal that bacoside-A blocked membrane interactions of Aß42, while formation of Aß42 oligomers was not disrupted. These interesting phenomena suggest that inhibition of Aß42 oligomer assembly into mature fibrils, and blocking membrane interactions of the oligomers are likely the underlying factors for ameliorating amyloid toxicity by bacoside-A and its putative physiological benefits.

Detection of Reactive Oxygen Species by a Carbon-Dot-Ascorbic Acid Hydrogel.

Detection of reactive oxygen species (ROS) is important in varied biological processes, disease diagnostics, and chemotherapeutic drug screening. We constructed a ROS sensor comprising an ascorbic-acid-based hydrogel encapsulating luminescent amphiphilic carbon-dots (C-dots). The sensing mechanism is based upon ROS-induced oxidation of the ascorbic acid units within the hydrogel scaffold; as a consequence, the hydrogel framework collapses resulting in aggregation of the C-dots and quenching of their luminescence. The C-dot-hydrogel platform exhibits high sensitivity and detected ROS generated chemically in solution and in actual cell environments. We demonstrate application of the C-dot-hydrogel for evaluating the efficacy of a chemotherapeutic substance, underscoring the potential of the system for drug screening applications.

Bifunctional Carbon-Dot-WS2 Nanorods for Photothermal Therapy and Cell Imaging.

Multifunctional nanoparticles have attracted significant interest as biomedical vehicles, combining diagnostic, imaging, and therapeutic properties. We describe herein the construction of new nanoparticle conjugates comprising WS2 nanorods (NRs) coupled to fluorescent carbon dots (C-dots). We show that the WS2 -C-dot hybrids integrate the unique physical properties of the two species, specifically the photothermal activity of the WS2 NRs upon irradiation with near-infrared (NIR) light and the excitation-dependent luminescence emission of the C-dots. The WS2 -C-dot NRs have been shown to be non-cytotoxic and have been successfully employed for multicolour cell imaging and targeted cell killing under NIR irradiation, pointing to their potential utilization as effective therapeutic vehicles.

Carbon-Dot/Silver-Nanoparticle Flexible SERS-Active Films.

Development of effective platforms for surface enhanced Raman scattering (SERS) sensing has mostly focused on fabrication of colloidal metal surfaces and tuning of their surface morphologies, designed to create "hot spots" in which plasmonic fields yield enhanced SERS signals. We fabricated distinctive SERS-active flexible films comprising polydimethylsiloxane (PDMS) embedding carbon dots (C-dots) and coated with silver nano-particles (Ag NPs). We show that the polymer-associated Ag NPs and C-dots intimately affected the physical properties of each other. In particular, the C-dot-Ag-NP-polymer films exhibited SERS properties upon deposition of versatile targets, both conventional SERS-active dyes as well as bacterial samples. We show that the SERS response was correlated to the formation C-dots within the polymer film and the physical proximity between the C-dots and Ag NPs, indicating that coupling between the plasmonic fields of the Ag NPs and C-dots' excitons constituted a prominent factor in the SERS properties.

Bacoside-A, an anti-amyloid natural substance, inhibits membrane disruption by the amyloidogenic determinant of prion protein through accelerating fibril formation.

Bacosides, class of compounds extracted from the Bacopa monniera plant, exhibit interesting therapeutic properties, particularly enhancing cognitive functions and putative anti-amyloid activity. We show that bacoside-A exerted significant effects upon fibrillation and membrane interactions of the amyloidogenic fragment of the prion protein [PrP(106-126)]. Specifically, when co-incubated with PrP(106-126), bacoside-A accelerated fibril formation in the presence of lipid bilayers and in parallel inhibited bilayer interactions of the peptide aggregates formed in solution. These interesting phenomena were studied by spectroscopic and microscopic techniques, which suggest that bacoside A-promoted fibrillation reduced the concentration of membrane-active pre-fibrillar species of the prion fragment. This study suggests that induction of fibril formation and corresponding inhibition of membrane interactions are likely the underlying factors for ameliorating amyloid protein toxicity by bacoside-A.

Lipid-Bilayer Dynamics Probed by a Carbon Dot-Phospholipid Conjugate.

Elucidating the dynamic properties of membranes is important for understanding fundamental cellular processes and for shedding light on the interactions of proteins, drugs, and viruses with the cell surface. Dynamic studies of lipid bilayers have been constrained, however, by the relatively small number of pertinent molecular probes and the limited physicochemical properties of the probes. We show that a lipid conjugate comprised of a fluorescent carbon dot (C-dot) covalently attached to a phospholipid constitutes a versatile and effective vehicle for studying bilayer dynamics. The C-dot-modified phospholipids readily incorporated within biomimetic membranes, including solid-supported bilayers and small and giant vesicles, and inserted into actual cellular membranes. We employed the C-dot-phospholipid probe to elucidate the effects of polymyxin-B (a cytolytic peptide), valproic acid (a lipophilic drug), and amyloid-ß (a peptide associated with Alzheimer's disease) upon bilayer fluidity and lipid dynamics through the application of various biophysical techniques.

Pomegranate Juice Polyphenols Induce Macrophage Death via Apoptosis as Opposed to Necrosis Induced by Free Radical Generation: A Central Role for Oxidative Stress.

At high concentrations, polyphenols induce cell death, and the polyphenols-rich pomegranate juice (PJ), known for its antioxidative/antiatherogenic properties, can possibly affect cell death, including macrophage death involved in atherogenesis. In the present study, apoptotic/necrotic macrophage death was analyzed in J774A.1 macrophages and in peritoneal macrophages isolated from atherosclerotic apoE-/- mice treated with PJ. The effects of PJ were compared with those of the free radical generator 2, 2'-azobis (2-amidinopropane) dihydrochloride (AAPH). Both PJ and AAPH significantly increased J774A.1 macrophage death; however, flow cytometric and microscopic analyses using annexin V/propidium iodide revealed that PJ increased the early apoptosis of the macrophage dose dependently (up to 2.5-fold, P < 0.01), whereas AAPH caused dose-dependent increases in late apoptosis/necrosis (up to 12-fold, P < 0.001). Unlike PJ, AAPH-induced macrophage death was associated with increased intracellular oxidative stress (up to 7-fold, P < 0.001) and with lipid stress demonstrated by triglyceride accumulation (up to 3-fold, P < 0.01) and greater chromatic vesicle response to culture medium (up to 5-fold, P < 0.001). Accordingly, recombinant paraoxonase 1, which hydrolyzes oxidized lipids, attenuated macrophage death induced by AAPH, but not by PJ. Similar apoptotic and oxidative effects were found in macrophages from apoE-/- mice treated with PJ or AAPH. As macrophage apoptotic/necrotic death has considerable impact on atherosclerosis progression, these findings may provide novel mechanisms for the antiatherogenicity of PJ.

Imaging Pseudomonas aeruginosa Biofilm Extracellular Polymer Scaffolds with Amphiphilic Carbon Dots.

Biofilm formation is a critical facet of pathogenesis and resilience of human, animal, and plant bacteria. Extracellular polymeric substances (EPS) constitute the physical scaffolding for bacterial biofilms and thus play central roles in their development and virulence. We show that newly synthesized amphiphilic fluorescent carbon dots (C-dots) readily bind to the EPS scaffold of Pseudomonas aeruginosa, a major biofilm-forming pathogen, resulting in unprecedented microscopic visualization of the EPS structural features. Fluorescence microscopy analysis utilizing the C-dots reveals that the P. aeruginosa EPS matrix exhibits a remarkable dendritic morphology. The experiments further illuminate the growth kinetics of the EPS and the effect of external factors such as temperature. We also show that the amphiphilic C-dot platform enabled screening of substances disrupting biofilm development, specifically quorum sensing inhibitors.

Imaging Cancer Cells Expressing the Folate Receptor with Carbon Dots Produced from Folic Acid.

Development of new imaging tools for cancer cells in vitro and in vitro is important for advancing cancer research, elucidating drug effects upon cancer cells, and studying cellular processes. We showed that fluorescent carbon dots (C-dots) synthesized from folic acid can serve as an effective vehicle for imaging cancer cells expressing the folate receptor on their surface. The C-dots, synthesized through a simple one-step process from folic acid as the carbon source, exhibited selectivity towards cancer cells displaying the folate receptor, making such cells easily distinguishable in fluorescence microscopy imaging. Biophysical measurements and competition experiments both confirmed the specific targeting and enhanced uptake of C-dots by the folate receptor-expressing cells. The folic acid-derived C-dots were not cytotoxic, and their use in bioimaging applications could aid biological studies of cancer cells, identification of agonists/antagonists, and cancer diagnostics.

Tuneable light-emitting carbon-dot/polymer flexible films prepared through one-pot synthesis.

Development of efficient, inexpensive, and environmentally-friendly light emitters, particularly devices that produce white light, have drawn intense interest due to diverse applications in the lighting industry, photonics, solar energy, and others. We present a simple strategy for the fabrication of flexible transparent films exhibiting tuneable light emission through one-pot synthesis of polymer matrixes with embedded carbon dots assembled in situ. Importantly, different luminescence colours were produced simply by preparing C-dot/polymer films using carbon precursors that yielded C-dots exhibiting distinct fluorescence emission profiles. Furthermore, mixtures of C-dot precursors could be also employed for fabricating films exhibiting different colours. In particular, we successfully produced films emitting white light with attractive properties (i.e."warm" white light with a high colour rendering index) - a highly sought after goal in optical technologies.

Toxicity inhibitors protect lipid membranes from disruption by Aß42.

Although the precise molecular factors linking amyloid ß-protein (Aß) to Alzheimer's disease (AD) have not been deciphered, interaction of Aß with cellular membranes has an important role in the disease. However, most therapeutic strategies targeting Aß have focused on interfering with Aß self-assembly rather than with its membrane interactions. Here, we studied the impact of three toxicity inhibitors on membrane interactions of Aß42, the longer form of Aß, which is associated most strongly with AD. The inhibitors included the four-residue C-terminal fragment Aß(39-42), the polyphenol (-)-epigallocatechin-3-gallate (EGCG), and the lysine-specific molecular tweezer, CLR01, all of which previously were shown to disrupt different steps in Aß42 self-assembly. Biophysical experiments revealed that incubation of Aß42 with each of the three modulators affected membrane interactions in a distinct manner. Interestingly, EGCG and CLR01 were found to have significant interaction with membranes themselves. However, membrane bilayer disruption was reduced when the compounds were preincubated with Aß42, suggesting that binding of the assembly modulators to the peptide attenuated their membrane interactions. Importantly, our study reveals that even though the three tested compounds affect Aß42 assembly differently, membrane interactions were significantly inhibited upon incubation of each compound with Aß42, suggesting that preventing the interaction of Aß42 with the membrane contributes substantially to inhibition of its toxicity by each compound. The data suggest that interference with membrane interactions is an important factor for Aß42 toxicity inhibitors and should be taken into account in potential therapeutic strategies, in addition to disruption or remodeling of amyloid assembly.

Bacterial detection with amphiphilic carbon dots.

New bacterial detection and imaging methods are desirable for diagnostics and healthcare applications, as well as in basic scientific research. We present a simple analytical platform for bacterial detection and imaging based upon attachment of amphiphilic carbon dots (CDs) to bacterial cells. We show that CDs functionalized with hydrocarbon chains readily bind to bacterial cells following short incubation and enable detection of bacteria through both fluorescence spectroscopy and microscopy. Importantly, we demonstrate that the intensity and spectral position of the carbon dots' fluorescence depend upon bacterial species, providing a tool for distinguishing among bacteria even in cases of mixed bacterial populations. Moreover, bacterial labelling with the amphiphilic CDs enables visualization of physiological processes such as cell division.

Unilamellar vesicles from amphiphilic graphene quantum dots.

Graphene quantum dots (GQDs) have attracted considerable interest due to their unique physicochemical properties and various applications. For the first time it is shown that GQDs surface-functionalized with hydrocarbon chains (i.e., amphiphilic GQDs) self-assemble into unilamellar spherical vesicles in aqueous solution. The amphiphilic GQD vesicles exhibit multicolor luminescence that can be readily exploited for membrane studies by fluorescence spectroscopy and microscopy. The GQD vesicles were used for microscopic analysis of membrane interactions and disruption by the peptide beta-amyloid.