Computational approaches for modeling and structural design of biological systems: A comprehensive review.

The convergence of biology and computational science has ushered in a revolutionary era, revolutionizing our understanding of biological systems and providing novel solutions to global problems. The field of genetic engineering has facilitated the manipulation of genetic codes, thus providing opportunities for the advancement of innovative disease therapies and environmental enhancements. The emergence of bio-molecular simulation represents a significant advancement in this particular field, as it offers the ability to gain microscopic insights into molecular-level biological processes over extended periods. Biomolecular simulation plays a crucial role in advancing our comprehension of organismal mechanisms by establishing connections between molecular structures, interactions, and biological functions. The field of computational biology has demonstrated its significance in deciphering intricate biological enigmas through the utilization of mathematical models and algorithms. The process of decoding the human genome has resulted in the advancement of therapies for a wide range of genetic disorders, while the simulation of biological systems contributes to the identification of novel pharmaceutical compounds. The potential of biomolecular simulation and computational biology is vast and limitless. As the exploration of the underlying principles that govern living organisms progresses, the potential impact of this understanding on cancer treatment, environmental restoration, and other domains is anticipated to be transformative. This review examines the notable advancements achieved in the field of computational biology, emphasizing its potential to revolutionize the comprehension and enhancement of biological systems.

Green Synthesis of Magnesium Oxide Nanoparticles by Using Abrus precatorius Bark Extract and Their Photocatalytic, Antioxidant, Antibacterial, and Cytotoxicity Activities.

The current research is concerned with the synthesis of magnesium oxide (MgO) nanoparticles (NPs) from Abrus precatorius L. bark extract via the green chemistry method. The synthesized MgO NPs was confirmed by using several characterization methods like XRD, FTIR, SEM, TEM, and UV-visible analysis. The synthesized MgO NPs displayed a small particle size along with a specific surface area. Abrus precatorius bark synthesized MgO NPs with a higher ratio of dye degradation, and antioxidant activity showed a higher percentage of free radical scavenging in synthesized MgO NPs. Zebrafish embryos were used as a model organism to assess the toxicity of the obtained MgO nanoparticles, and the results concluded that the MgO NPs were nontoxic. In addition, the anticancer properties of MgO nanoparticles were analyzed by using a human melanoma cancer cell line (A375) via MTT, XTT, NRU, and LDH assessment. MgO NPs treated a human melanoma cancer cell line and resulted in apoptosis and necrosis based on the concentration, which was confirmed through a genotoxicity assay. Moreover, the molecular mechanisms in necrosis and apoptosis were conferred to depict the association of magnesium oxide nanoparticles with the human melanoma cancer cell line. The current study on MgO NPs showed a broad-scope understanding of the use of these nanoparticles as a medicinal drug for melanoma cancer via its physiological mechanism and also a novel route to obtain MgO NPs by using the green chemistry method.

Bright Luminescent Carbon Dots for Multifunctional Selective Sensing and Imaging Applications in Living Cells.

Luminescent carbon dots (CDs) have become attractive materials because of their superior photophysical properties and various potential applications. However, most of the formerly developed CDs only have strong blue emission, which limits their further applications, particularly in bioimaging. Herein luminescent CDs have been successfully synthesized via a one-pot solvothermal process using 4-bromoaniline and ethylenediamine as starting materials. The luminescent CDs emit strong green fluorescence with high quantum yield as well as excellent biocompatibility and biolabeling potentials. At first, the luminescent CDs exhibited high selectivity for phosgene with a turn-off fluorescence detection. The limit of detection was 81 nM, which is sensitive for the determination of phosgene over other competing toxic pollutants. In addition, the luminescent CDs have shown a three-state "on-off-on" emission with the stepwise addition of Ag+ and cysteine (Cys). Luminescent CDs show fluorescence quenching by Ag+ and fluorescence regaining with further addition of Cys, with lower detection limits of 3.9 µM (Ag+) and 3.4 µM (Cys), respectively. The luminescent CDs were utilized to obtain a clear fingerprint. During the drying process, the coffee ring effect and electrostatic interaction between the positive surface charge of amine-functionalized CDs and negatively charged fingerprint residues facilitate the formation of clear fingerprints on different platforms.

Cysteamine-capped gold-copper nanoclusters for fluorometric determination and imaging of chromium(VI) and dopamine.

Highly emissive cysteamine-capped gold-copper bimetallic nanoclusters (CA-AuCu NCs) with a quantum yield of 18% were synthesized via one-pot anti-galvanic reduction. The CA-AuCu NCs were characterized by HR-TEM, XPS, FTIR, MALDI-TOF mass spectrometry, DLS, and zeta potential analyses. The NCs are shown to be viable fluorescent probes for Cr(VI) ions and dopamine (DA) via quenching of the blue fluorescence, typically measured at excitation/emission wavelengths of 350/436 nm. During DA recognition, a dark brown color appears, which is distinguishable from that of Cr(VI) detection. The aggregation induced quenching due to electron transfer was demonstrated by photoluminescence, HR-TEM, FTIR, DLS, and zeta potential interrogations. In buffer of pH 7, response is linear in the 0.2 ~ 100 µM for Cr(VI) and from 0.4 ~ 250 µM for DA. The respective detection limits are 80 and 135 nM. The method was applied to the determination of both Cr(VI) and DA in (spiked) tap, lake and sea water, and in human urine samples. The low toxicity of CA-AuCu NCs was validated by the MTT assay, and their responses to Cr(VI) ions and DA was also proven by Raw 264.7 cell imaging. Graphical abstractCysteamine capped Au-Cu nanoclusters (CA-AuCu NCs) were synthesized via one-pot anti-galvanic reduction and utilized in sensing of Cr(VI) ions and dopamine (DA) with demonstrated real/urine and cell imaging applications.

FRET-based dual channel fluorescent probe for detecting endogenous/exogenous H2O2/H2S formation through multicolor images.

We have developed a FRET-based fluorescent probe (PHS1) as a combination of two different fluorophores (coumarin and naphthalimide); which can detect both exogenous and endogenous H2S and H2O2 in live cells through multicolor images. The precise overlap between UV-absorption of naphthalimide and the emission band of coumarin in probe PHS1 allows the acquisition of the self-calibrated information of dual analytes through FRET-based imaging. The UV-Vis absorption (λabs 390 nm) and fluorescence emission (λem 460 nm) of probe PHS1 in the presence of H2O2 are increased ∽35- fold and ∽15-fold respectively. It also allows the estimation of the levels of H2S through enhancement of emission intensity at 550 nm. The probe PHS1 exhibits high stability against various analytes, including various pH (4-9.5). The cell viability assay data indicate that the probe is not harmful to the cancer cells. The nontoxic nature of the probe PHS1 encourages application for cancer cell labeling. The probe PHS1 can detect the level of endogenous H2O2, H2S, and H2O2/H2S in cancer cells through blue, green and FRET-based green channel imaging. PHS1 is a unique probe, has potential application for diagnosing cancer by providing information on the level of dual analytes (H2S, H2O2) in cancer cells.

In Vitro and In Vivo Approach of Hydrogen-Sulfide-Responsive Drug Release Driven by Azide-Functionalized Mesoporous Silica Nanoparticles.

Cancer has become a major cause of human death in many countries. Generally, chemotherapy is the main treatment for cancer, but it may kill both cancerous cells as well as normal cells that cause serious side effects in the patient due to lack of specific targeting for cancerous cells. In order to achieve better efficiency in the cancer treatment, the development of targeted drug delivery platform has been a goal for a long time. Herein, we constructed folic acid decorated azide functionalized biocompatible mesoporous silica nanoparticles (MSNPs) to target tumor cells through folate receptor (FR), a widely expressed receptor in cancer cells. In colon and ovarian cancer cells, high endogenous H2S levels are found. They can be used as a trigger for the azide reduction, which leads to the cleavage of ester linkage and results in DOX release from MSNP nanocarriers. Additionally, confocal cell images of HCT-116, HT-29, A2780, SKOV3, and HeLa cells treated with nanoparticles revealed an effective internalization of MSNPs in these cells. Interestingly, DOX-loaded MSNP-N3-FA-treated HT-29 cells showed a significant decrease in the cell viability, whereas, there was no substantial change in HeLa cells. We also demonstrated that DOX-loaded MSNP-N3-FA has superior in vivo chemotherapy efficacy compared to free DOX. These observations indicated that the designed nanocarriers on MSNP-N3-FA specifically respond in the presence of H2S. MSNP-N3-FA is the first potential nanocarrier for endogenous H2S-based efficient DOX release for colon and ovarian cancers.

Redox Stimuli Delivery Vehicle Based on Transferrin-Capped MSNPs for Targeted Drug Delivery in Cancer Therapy.

Cancer has become one of the major diseases of human health around the world. Conventional antitumor drugs cannot specifically target cancers and result in serious side effects. To achieve better therapy, innovative functional drug delivery platforms that will aid specific targeting for cancer cells need to be developed. In this study, transferrin (Tf), which can target cancer cells, is covalently anchored onto the surface of MSNPs via disulfide linkage, which is used for glutathione-triggered intracellular drug release in tumor cells. The successful functionalization of redox-responsive MSNPs is confirmed by using BET/BJH, TEM, TGA, NMR, and FT-IR (BET, Brunauer-Emmett-Teller; BJH, Barrett-Joyner-Halenda). In addition, polyethylene glycol (PEG) is further grafted onto the surface of MSNPs to improve the biocompatibility and stability under physiological conditions for longer blood circulation. Our in vitro studies demonstrate that DOX-loaded MSNP-SS-Tf@PEG can selectively be internalized into cancer cells via Tf/Tf receptor interactions, and then, DOX is released in HT-29 and MCF-7 cells triggered by high GSH concentration in tumor cells. Remarkably, in vivo studies demonstrate that DOX-loaded MSNP-SS-Tf@PEG can significantly inhibit tumor growth with minimized side effects through cell apoptosis determined by TUNEL assay, whereas MSNP-SS-Tf@PEG revealed no significant inhibition. In conclusion, DOX-MSNP-SS-Tf@PEG with active targeting moieties and a redox-responsive strategy has been demonstrated as a great effective drug carrier for tumor therapy in vitro and in vivo.

Fluorescent coumarin-based probe for cysteine and homocysteine with live cell application.

Cysteine (Cys) and homocysteine (Hcy) are two of important biological thiols and function as important roles in several biological processes. The development of Cys and Hcy probes will help to explore the functions of biothiols in biological systems. In this work, a new coumarin-based probe AC, containing an acryloyl moiety, was developed for Cys and Hcy detection in cells. Cys and Hcy undergo a nucleophilic addition and subsequent cyclization reaction to remove to the acryloyl group and yield a fluorescent product, 7-hydroxylcomuarin. The probe AC showed good selectivity for cysteine and homocysteine over glutathione and other amino acids and had low detection limits of 65nM for Cys and 79nM for Hcy, respectively. Additionally, confocal imaging experiments demonstrated that the probe AC can be applied to visualize Cys and Hcy in living cells.