Mushroom-Derived Bioactive Molecules as Immunotherapeutic Agents: A Review

Mushrooms with enhanced medicinal properties focus on finding such compounds that could modulate the human body’s immune systems. Mushrooms have antimicrobial, antidiabetic, antiviral, hepatoprotective, antitumor, and immunomodulatory properties due to the presence of various bioactive components. β-glucans are the major constituent of the mushroom cell wall and play a significant role in their biological activity. This review described the techniques used in the extraction of the active ingredients from the mushroom. We highlighted the structure of the bioactive polysaccharides present in the mushrooms. Therapeutic applications of different mushrooms were also described. It is interesting to note that mushrooms have the potential sources of many bioactive products that can regulate immunity. Thus, the development of functional medicinal food based on the mushroom is vital for human welfare.     

Structural evolution and stability of hydrogenated Li(n) (n = 1-30) clusters: a density functional study

The structure and electronic and optical properties of hydrogenated lithium clusters Li(n)H(m) (n = 1-30, m ≤ n) have been investigated by density functional theory (DFT). The structural optimizations are performed with the Becke 3 Lee-Yang-Parr (B3LYP) exchange-correlation functional with 6-311G++(d, p) basis set. The reliability of the method employed has been established by excellent agreement with computational and experimental data, wherever available. The turn over from two- to three-dimensional geometry in Li(n)H(m) clusters is found to occur at size n = 4 and m = 3. Interestingly, a rock-salt-like face-centered cubic structure is seen in Li(13)H(14). The sequential addition of hydrogen to small-sized Li clusters predicted regions of regular lattice in saturated hydrogenated clusters. This led us to focus on large-sized saturated clusters rather than to increase the number of hydrogen atoms monotonically. The lattice constants of Li(9)H(9), Li(18)H(18), Li(20)H(20), and Li(30)H(30) calculated at their optimized geometry are found to gradually approach the corresponding bulk values of 4.083. The sequential addition of hydrogen stabilizes the cluster, irrespective of the cluster size. A significant increase in stability is seen in the case of completely hydrogenated clusters, i.e., when the number of hydrogen atoms equals Li atoms. The enhanced stability has been interpreted in terms of various electronic and optical properties like adiabatic and vertical ionization potential, HOMO-LUMO gap, and polarizability.     

Novel glycoconjugates of diospyrin, a quinonoid plant product: synthesis and evaluation of cytotoxicity against human malignant melanoma (A375) and laryngeal carcinoma (Hep2)

Glycoside derivatives of diospyrin (1) were synthesized for the first time, and the cytotoxicity of the novel compounds vis-à-vis their precursors were evaluated against two human cancer cell lines, viz. malignant melanoma (A375) and laryngeal carcinoma (Hep2). The IC(50) values were in the low micromolar range for all the compounds tested, and A375 cells showed comparatively greater sensitivity than Hep2. Most of the compounds exhibited enhanced activity as compared to the plant-derived quinonoid precursor of the series (1), while the aminophenyl mannosyl (6) was found to be the most effective derivative. In A375 cells, 6 (IC(50) = 0.02 microM) showed the maximum increase in cytotoxicity (approximately 35-fold) over that of 1 (IC(50) = 0.82 microM). Again, when the glycosides were evaluated at a given concentration (0.1 microM) for their relative capacity to generate ROS from A375 cells, the compound 6 could produce the highest amount of ROS. Incidentally, this derivative also showed a comparatively lower toxicity (IC(50) approximately 41 microM) when tested against normal human peripheral blood mononuclear cells, indicating a fair prospect of its development as a novel chemotherapeutic agent for the treatment of malignant melanoma.     

Wipe sampling procedure coupled to LC–MS/MS analysis for the simultaneous determination of 10 cytotoxic drugs on different surfaces

A simple wipe sampling procedure was developed for the surface contamination determination of ten cytotoxic drugs: cytarabine, gemcitabine, methotrexate, etoposide phosphate, cyclophosphamide, ifosfamide, irinotecan, doxorubicin, epirubicin and vincristine. Wiping was performed using Whatman filter paper on different surfaces such as stainless steel, polypropylene, polystyrol, glass, latex gloves, computer mouse and coated paperboard. Wiping and desorption procedures were investigated: The same solution containing 20% acetonitrile and 0.1% formic acid in water gave the best results. After ultrasonic desorption and then centrifugation, samples were analysed by a validated liquid chromatography coupled to tandem mass spectrometry (LC–MS/MS) in selected reaction monitoring mode. The whole analytical strategy from wipe sampling to LC–MS/MS analysis was evaluated to determine quantitative performance. The lowest limit of quantification of 10 ng per wiping sample (i.e. 0.1 ng cm⁻²) was determined for the ten investigated cytotoxic drugs. Relative standard deviation for intermediate precision was always inferior to 20%. As recovery was dependent on the tested surface for each drug, a correction factor was determined and applied for real samples. The method was then successfully applied at the cytotoxic production unit of the Geneva University Hospitals pharmacy.     

Graphene Oxide-Based Stimuli-Responsive Platforms for Biomedical Applications

Graphene is a two-dimensional sp² hybridized carbon material that has attracted tremendous attention for its stimuli-responsive applications, owing to its high surface area and excellent electrical, optical, thermal, and mechanical properties. The physicochemical properties of graphene can be tuned by surface functionalization. The biomedical field pays special attention to stimuli-responsive materials due to their responsive abilities under different conditions. Stimuli-responsive materials exhibit great potential in changing their behavior upon exposure to external or internal factors, such as pH, light, electric field, magnetic field, and temperature. Graphene-based materials, particularly graphene oxide (GO), have been widely used in stimuli-responsive applications due to their superior biocompatibility compared to other forms of graphene. GO has been commonly utilized in tissue engineering, bioimaging, biosensing, cancer therapy, and drug delivery. GO-based stimuli-responsive platforms for wound healing applications have not yet been fully explored. This review describes the effects of different stimuli-responsive factors, such as pH, light, temperature, and magnetic and electric fields on GO-based materials and their applications. The wound healing applications of GO-based materials is extensively discussed with cancer therapy and drug delivery.     

A 3D Bioprinted Nanoengineered Hydrogel with Photoactivated Drug Delivery for Tumor Apoptosis and Simultaneous Bone Regeneration via Macrophage Immunomodulation

One of the significant challenges in bone tissue engineering (BTE) is the healing of traumatic tissue defects owing to the recruitment of local infection and delayed angiogenesis. Herein, a 3D printable multi-functional hydrogel composing polyphenolic carbon quantum dots (CQDs, 100 µg mL⁻¹) and gelatin methacryloyl (GelMA, 12 wt%) is reported for robust angiogenesis, bone regeneration and anti-tumor therapy. The CQDs are synthesized from a plant-inspired bioactive molecule, 1, 3, 5-trihydroxybenzene. The 3D printed GelMA-CQDs hydrogels display typical shear-thinning behavior with excellent printability. The fabricated hydrogel displayed M2 polarization of macrophage (Raw 264.7) cells via enhancing anti-inflammatory genes (e.g., IL-4 and IL10), and induced angiogenesis and osteogenesis of human bone mesenchymal stem cells (hBMSCs). The bioprinted hBMSCs are able to produce vessel-like structures after 14 d of incubation. Furthermore, the 3D printed hydrogel scaffolds also show remarkable near infra-red (NIR) responsive properties under 808 nm NIR light (1.0 W cm⁻²) irradiation with controlled release of antitumor drugs (≈49%) at pH 6.5, and thereby killing the osteosarcoma cells. Therefore, it is anticipated that the tissue regeneration and healing ability with therapeutic potential of the GelMA-CQDs scaffolds may provide a promising alternative for traumatic tissue regeneration via augmenting angiogenesis and accelerated immunomodulation.     

Aggregation-Induced Emission-Based Sensing Platform for Selective Detection of Zn2+: Experimental and Theoretical Investigations

Fluorescent chemosensors with aggregation induced emission enhancement (AIEE) emerge as promising tools in the field of sensing materials. Herein, we report the design, synthesis and applicability of a Schiff base chemosensor 1-(benzo[1,3]dioxol-4-ylmethylene-hydrazonomethyl)-naphthalen-2-ol ( Hbdhn ) of AIE characteristics that exhibits highly effective and selective response towards Zn²⁺. The sensing effect of Hbdhn was evaluated by means of absorption/emission spectra and corresponding underlying photophysical mechanisms were proposed based on extensive quantum-chemical (TD)DFT calculations. The aggregated states in different DMSO/H₂O ratios and in a presence of Zn²⁺ were examined by fluorescence lifetime measurements, dynamic light scattering and scanning electron microscopy studies. The bioimaging abilities of Hbdhn were evaluated for Zn²⁺ in HepG2 cancer cells. The results demonstrate instant, stable in time and reproducible, colorimetric turn-on response with superb selectivity and sensitivity of Hbdhn towards Zn²⁺, based on chelation enhanced fluorescence mechanism. AIEE improves further Hbdhn properties, leading to strong, long-lived fluorescence, with appearance of rod-like particles, in 90 % of water in DMSO and only 10 % of water in DMSO in the presence of Zn²⁺. All these features combined with successful biomaging studies make Hbdhn one of the most promising candidate for practical applications among recently proposed related systems.     

Topologically Protected and Highly Localized Surface Waves in Gyro-Electromagnetic Metamaterials

Topological insulators are internally insulating but allow topologically protected surface waves at the boundary. In this work, the photonic analogue of topologically protected surface states in gyro-electromagnetic metamaterials are discovered. It is analytically and numerically demonstrated that the surface waves appear not only in the k-space common gap regions between the bulk states of the metamaterials and the vacuum state, but even can exist in an infinitely extended k-space. Such surface waves have extremely large wave vectors along the propagation direction with high field localization on the surface. It is believed that the high field localization of surface waves could improve the compactness of photonic devices and facilitate the integration of photonic circuits.     

Recent Advances in 3D Printing of Photocurable Polymers: Types,Mechanism, and Tissue Engineering Application

The conversion of liquid resin into solid structures upon exposure to light of a specific wavelength is known as photopolymerization. In recent years, photopolymerization-based 3D printing has gained enormous attention for constructing complex tissue-specific constructs. Due to the economic and environmental benefits of the biopolymers employed, photo-curable 3D printing is considered an alternative method for replacing damaged tissues. However, the lack of suitable bio-based photopolymers, their characterization, effective crosslinking strategies, and optimal printing conditions are hindering the extensive application of 3D printed materials in the global market. This review highlights the present status of various photopolymers, their synthesis, and their optimization parameters for biomedical applications. Moreover, a glimpse of various photopolymerization techniques currently employed for 3D printing is also discussed. Furthermore, various naturally derived nanomaterials reinforced polymerization and their influence on printability and shape fidelity are also reviewed. Finally, the ultimate use of those photopolymerized hydrogel scaffolds in tissue engineering is also discussed. Taken together, it is believed that photopolymerized 3D printing has a great future, whereas conventional 3D printing requires considerable sophistication, and this review can provide readers with a comprehensive approach to developing light-mediated 3D printing for tissue-engineering applications.