Biomembrane camouflaged nanoparticles: A paradigm shifts in targeted drug delivery system.

Targeted drug delivery has emerged as a pivotal approach within precision medicine, aiming to optimize therapeutic efficacy while minimizing systemic side effects. Advanced biomimetic membrane-coated formulations have garnered significant interest from researchers as a promising strategy for targeted drug delivery, site-specific accumulation and heightened therapeutic outcomes. Biomimetic nanotechnology is able to retain the biological properties of the parent cell thus are able to exhibit superior targeting compared to conventional formulations. In this review, we have described different types of cell membrane camouflaged NPs. Mechanism of isolation and coating of the membranes along with the applications of each type of membrane and their mechanism to reach the desired site. Furthermore, a fusion of different membranes in order to prepare hybrid membrane biomimetic NPs which could possess better efficacy is discussed in detail in the review. Later, applications of the hybrid membrane-cloaked NPs along with current development were discussed in detail along with the challenges associated with it. Although membrane-cloaked NPs are currently in the preliminary stage of development, there is a huge potential to explore this biodegradable and biocompatible delivery system.

Endoplasmic Reticulum Stress Disrupts Mitochondrial Bioenergetics, Dynamics and Causes Corneal Endothelial Cell Apoptosis.

Purpose: Endoplasmic reticulum (ER) and mitochondrial stress are independently associated with corneal endothelial cell (CEnC) loss in many corneal diseases, including Fuchs' endothelial corneal dystrophy (FECD). However, the role of ER stress in mitochondrial dysfunction contributing to CEnC apoptosis is unknown. The purpose of this study is to explore the crosstalk between ER and mitochondrial stress in CEnC. Methods: Human corneal endothelial cell line (HCEnC-21T) and human corneal endothelial tissues were treated with ER stressor tunicamycin. ER stress-reducing chemical 4-phenyl butyric acid (4-PBA) was used in HCEnC-21T after tunicamycin. Fuchs' corneal endothelial cell line (F35T) was used to determine differential activation of ER stress with respect to HCEnC-21T at the baseline. ER stress, mitochondrial-mediated intrinsic apoptotic, mitochondrial fission, and fusion proteins were determined using immunoblotting and immunohistochemistry. Mitochondrial bioenergetics were assessed by mitochondrial membrane potential (MMP) loss and ATP production at 48 hours after tunicamycin. Mitochondria dynamics (shape, area, perimeter) were also analyzed at 24 hours using transmission electron microscopy. Results: Treatment of HCEnC-21T cell line with tunicamycin activated three ER stress pathways (PERK-eIF2α-CHOP, IRE1α-XBP1, and ATF6), reduced cell viability, upregulated mitochondrial-mediated intrinsic apoptotic molecules (cleaved caspase 9, caspase 3, PARP, Bax, cytochrome C), downregulated anti-apoptotic Bcl-2 protein, initiated mitochondrial dysfunction by loss of MMP and lowering of ATP production, and caused mitochondrial swelling and fragmentation with increased expression of mitochondrial fission proteins (Fis1 and p-Drp1). Fuchs' CEnC (F35T) cell line also showed activation of the ER stress-related proteins (p-eIF2α, GRP78, CHOP, XBP1) compared to HCEnC-21T at the baseline. The 4-PBA ameliorated cell loss and reduced cleaved caspase 3 and 9, thereby rescuing tunicamycin-induced cell death but not mitochondrial bioenergetics in HCEnC-21T cell line. Conclusions: Tunicamycin-induced ER stress disrupts mitochondrial bioenegetics, dynamics and contributes to the loss of CEnC viability. This novel study highlights the importance of ER-mitochondria crosstalk and its contribution to CEnCs apoptosis, seen in many corneal diseases, including FECD.

Connectedness of COVID vaccination with economic policy uncertainty, oil, bonds, and sectoral equity markets: evidence from the US.

We examine the connectedness of the COVID vaccination with the economic policy uncertainty, oil, bonds, and sectoral equity markets in the US within time and frequency domain. The wavelet-based findings show the positive impact of COVID vaccination on the oil and sector indices over various frequency scales and periods. The vaccination is evidenced to lead the oil and sectoral equity markets. More specifically, we document strong connectedness of vaccinations with communication services, financials, health care, industrials, information technology (IT) and real estate equity sectors. However, weak interactions exist within the vaccination-IT-services and vaccination-utilities pairs. Moreover, the effect of vaccination on the Treasury bond index is negative, whereas the economic policy uncertainty shows an interchanging lead and lag relation with vaccination. It is further observed that the interrelation between vaccination and the corporate bond index is insignificant. Overall, the impact of vaccination on the sectoral equity markets and economic policy uncertainty is higher than on oil and corporate bond prices. The study offers several important implications for investors, government regulators, and policymakers.

Distinct microRNA and protein profiles of extracellular vesicles secreted from myotubes from morbidly obese donors with type 2 diabetes in response to electrical pulse stimulation.

Lifestyle disorders like obesity, type 2 diabetes (T2D), and cardiovascular diseases can be prevented and treated by regular physical activity. During exercise, skeletal muscles release signaling factors that communicate with other organs and mediate beneficial effects of exercise. These factors include myokines, metabolites, and extracellular vesicles (EVs). In the present study, we have examined how electrical pulse stimulation (EPS) of myotubes, a model of exercise, affects the cargo of released EVs. Chronic low frequency EPS was applied for 24 h to human myotubes isolated and differentiated from biopsy samples from six morbidly obese females with T2D, and EVs, both exosomes and microvesicles (MV), were isolated from cell media 24 h thereafter. Size and concentration of EV subtypes were characterized by nanoparticle tracking analysis, surface markers were examined by flow cytometry and Western blotting, and morphology was confirmed by transmission electron microscopy. Protein content was assessed by high-resolution proteomic analysis (LC-MS/MS), non-coding RNA was quantified by Affymetrix microarray, and selected microRNAs (miRs) validated by real time RT-qPCR. The size and concentration of exosomes and MV were unaffected by EPS. Of the 400 miRs identified in the EVs, EPS significantly changed the level of 15 exosome miRs, of which miR-1233-5p showed the highest fold change. The miR pattern of MV was unaffected by EPS. Totally, about 1000 proteins were identified in exosomes and 2000 in MV. EPS changed the content of 73 proteins in exosomes, 97 in MVs, and of these four were changed in both exosomes and MV (GANAB, HSPA9, CNDP2, and ATP5B). By matching the EPS-changed miRs and proteins in exosomes, 31 targets were identified, and among these several promising signaling factors. Of particular interest were CNDP2, an enzyme that generates the appetite regulatory metabolite Lac-Phe, and miR-4433b-3p, which targets CNDP2. Several of the regulated miRs, such as miR-92b-5p, miR-320b, and miR-1233-5p might also mediate interesting signaling functions. In conclusion, we have used a combined transcriptome-proteome approach to describe how EPS affected the cargo of EVs derived from myotubes from morbidly obese patients with T2D, and revealed several new factors, both miRs and proteins, that might act as exercise factors.

Involvement of Type-I and Type-II Photodynamic Reactions in Photosensitization of Fragrance Ingredient 2-acetonaphthone.

2-Acetonaphthone (2-ACN) is a synthetic fragrance material used in various cosmetics as an adulterant. Due to its frequent use, we have conducted an in-depth study to understand the photosensitizing potential of 2-ACN. Results of this study illustrate that 2-ACN showed photodegradation in 4 h under ambient UV radiation (UVR) and sunlight exposure. It generated (1-25 µg mL-1 ) superoxide anion radical (O2 ·- ) and singlet oxygen (1 O2 ) in the presence of UVR/sunlight through in chemico and in vitro test systems. 2-ACN (10 µg mL-1 ) showed a 43.9% and 57.4% reduction in cell viability under UVA and sunlight, respectively. Photosensitized 2-ACN generated intracellular reactive oxygen species (ROS) (6-folds in UVA and 8-folds in sunlight), which compromises the endoplasmic reticulum and mitochondrial membrane potential leading to cell death. Acridine orange/ethidium bromide dual staining and annexin-V/PI uptake showed cell death caused via 2-ACN under UVR exposure. The above findings signify the role of ROS via Type-I and Type-II photodynamic pathways in photosensitization of 2-ACN that ultimately promotes photodamage of important cellular organelles leading to cell death. The study advocates that solar radiation should be avoided by the users after the application of cosmetic products containing 2-ACN.

UVR-induced phototoxicity mechanism of methyl N-methylanthranilate in human keratinocyte cell line.

Fragrances are used in almost every cosmetic product. International Fragrance Association (IFRA) is the regulatory body that controls the use of fragrances in cosmetic products. Methyl-N-methylanthranilate (DMA) is a naturally derived fragrance, commonly used in cosmetic products such as fine perfumes, skin care products, etc. But there is a lack of detailed study in terms of its phototoxic and photogenotoxicity mechanisms under UVA/sunlight exposure. In this study, we have shown that DMA photodegrades in 4 h under UVA (1.5 mW/cm2) and sunlight. DMA (0.0001%-0.0025%) significantly reduced the cell viability as demonstrated by NRU and MTT assays in a dose-dependent manner under UVA (5.4 J/cm2) and sunlight (1 h) exposure in the HaCaT cell line. It generated excessive intracellular ROS (superoxide anion radical via type-I photodynamic reaction), resulting in lysosomal destabilization and mitochondrial membrane depolarization. Photo-activated DMA caused DNA fragmentation as observed by olive tail moment. DNA double-strand breaks was demonstrated by phosphorylation of H2AX-histone protein and formation of photo-micronuclei in skin keratinocytes. Additionally, photo-activated DMA upregulated the oxidative stress marker gene hemeoxygenase-1 and apoptotic marker genes (cytochrome-C, caspase-3, caspase-9). Activated caspase-cascade pathway established that photo-activated DMA can potentially trigger apoptosis in the human skin cells.

Nabumetone induced photogenotoxicity mechanism mediated by ROS generation under environmental UV radiation in human keratinocytes (HaCaT) cell line.

Nabumetone (NB) is a non-steroidal anti-inflammatory drug (NSAID), prescribed for managing pain associated with acute/chronic rheumatoid arthritis, osteoarthritis and other musculoskeletal disorders. Though some incidences of photosensitivity have been reported, there is limited information available on its phototoxicity potential. In this study, NB photodegraded in a time-dependant manner (0-4 h) under UVA (1.5 mW/cm2), UVB (0.6 mW/cm2) and natural sunlight as observed through UV-vis spectrophotometer and the results were further confirmed with Ultra High-Performance Liquid Chromatography (UHPLC). Photosensitized NB generated reactive oxygen species (ROS) as observed by lipid peroxidation, suggesting oxidative degradation of lipids in cell membrane, thereby resulting in cell damage. MTT and NRU (neutral red uptake) assays revealed that NB induced phototoxicity in concentration-dependent manner (0.5, 1, 5, 10 µg/ml) under UVA, UVB and sunlight exposure (30 min) in human keratinocytes cell line (HaCaT), with significant phototoxicity at the concentration of 5 µg/ml. Photosensitized NB generated intracellular ROS, disrupted mitochondrial and lysosomal membrane integrity, resulting in cell death. UV-induced genotoxicity by NB was confirmed through micronuclei generation, γ-H2AX induction and cyclobutane pyrimidine dimer formation. This is the first study which showed the phototoxicity and photogenotoxicity potential of NB in HaCaT cell line. We also observed that photosensitized NB upregulated inflammatory markers, such as COX-2 and TNFα. This study proposes that sunlight exposure should be avoided by patients using nabumetone and proper guidance should be provided by clinicians regarding photosensitivity of drugs for better safety and efficacy.

Chitosan capping of CuO nanoparticles: Facile chemical preparation, biological analysis, and applications in dentistry.

This investigation is vital contribution to the healthcare system utilizing techniques of nanobiotechnology. It interestingly applies chitosan capped CuO nanoparticles in the field of medicine and restorative dentistry. The CuO nanoparticles and CuO-Chitosan nanoparticles are prepared by co-precipitation, and their characterization is performed using X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), scanning electron microscopy (SEM), transmission electron microscopy (TEM), and energy dispersive X-ray (EDX). The average crystallite size of these nanoparticles has been found to be in the dimensions of <40 nm and <35 nm, respectively. CuO-Chitosan nanoparticles show significant enhancement in in vitro antibacterial, antioxidant, cytotoxic, and antidiabetic activity as compared to CuO nanoparticles. In addition, the successful amalgamation of CuO nanoparticles and CuO-Chitosan nanoparticles into dentine bonding agents results in providing efficient remedy against secondary caries. CuO-Chitosan nanoparticles reinforced dental adhesive discs cause significant upsurge in reduction of Lactobacillus acidophillus and Streptococcus mutans. Also, the augmentation of mechanical properties, water sorption and solubility plus slow and sustained release profile and slight variation of shear bond strength is attained. Taken together, the chemically synthesized CuO nanoparticles and CuO-Chitosan nanoparticles have proven to be promising candidates having enormous potential to be utilized in drug delivery and nanotheranostics.

The current use of anti-cariogenic agents and fluoride agents to cure write spot lesion: A systematic analysis.

To find the best option to treat White Spot Lesion in existing caries treatments, and to identify the selected articles discussing etiology of caries along with White spot lesion. Null hypothesis was that "Only anticariogenic agent can cure White Spot Lesion". PRISMA guidelines were used to conduct the systematic analysis. An electronic customized search was performed using mesh terminologies on PubMed database based on inclusion criteria that included studies with; any treatment option that can treat or prevent WSL; and minimally invasive treatment options that may be altered to treat WSL. While exclusion criteria comprised studies with treatment of rampant caries, severe early childhood caries and root caries. Inclusion criteria for etiological factors incorporated studies with factors that lead to white spot lesion or carious lesion. Finally, therapeutic agents of dental caries were analyzed. Only the use of anti-cariogenic agent cannot cure White Spot Lesion. Hence study fails to prove the null hypothesis. Although combination of anti-cariogenic agents with a re-mineralizing agent can provide additional options for the treatment or prevention of WSL.

Photoexcited triclosan induced DNA damage and oxidative stress via p38 MAP kinase signaling involving type I radicals under sunlight/UVB exposure.

Triclosan (TCS) is an antimicrobial preservative used in personal care products. Here, we have studied the phototoxicity, photogenotoxicity of TCS and its molecular mechanism involving p38 mitogen activated protein kinase (MAPK) pathway under UVB/sunlight exposure. We found that TCS showed photodegradation and photoproducts formation under UVB/sunlight. In silico study suggests that photosensitized TCS loses its preservative property due to the formation of its photoproducts. Photosensitized TCS induces significant O2•-, •OH generation and lipid peroxidation via type-I photochemical reaction mechanism under UVB/sunlight exposure. We performed intracellular study of TCS on human skin keratinocytes (HaCaT cell-line) under the ambient intensity of UVB (0.6 mW/cm2) and sunlight exposure. Significant intracellular ROS generation was observed through DCFH2-DA/DHE assays along with a significant reduction in cell viability through MTT and NRU assays in photosensitized TCS. Photosensitized TCS also induces endoplasmic reticulum (ER) stress as shown through ER-tracker/DAPI staining and Ca2+ release. It further induced cell cycle arrest through the sub-G1 phase augmentation and caused lysosomal/mitochondrial destabilization. Photogenotoxicity was shown through significant tail DNA, micronuclei and cyclobutane pyrimidine dimers (CPDs) formations. Cell signaling mechanism implicated upregulated expression of cleaved Caspase-3, Bax, phospho-p38, phospho-JNK and cytochrome C, thereby downregulated Bcl-2 expressions. Results advocate that TCS induces phototoxic effects via type I mediated photodynamic mechanism and activation of MAPK pathway. We conclude that photoexcited TCS may be deleterious to human health at the ambient environmental intensities of sunlight reaching at the earth's surface. Therefore, it may be replaced by alternative safe preservative.

Microwave-assisted synthesis and evaluation of type 1 collagen-apatite composites for dental tissue regeneration.

The aim was to develop an economical and biocompatible collagen-based bioactive composite for tooth regeneration. Acid-soluble collagen was extracted and purified from fish scales. The design was innovated to molecularly tailor the surface charge sites of the nano-apatite providing chemical bonds with the collagen matrix via microwave irradiation technique. The obtained collagen was identified by sodium dodecyl sulfate polyacrylamide gel electrophoresis analysis. The composites were characterized by Fourier transform infrared spectroscopy, thermogravimetric analysis/differential scanning calorimetry, and scanning electron microscopy. MC3T3-E1 cell lines were used to assess the biological effects of these materials by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-tetra zolium bromide (MTT) assay. Indirect contact test was performed by extracting representative elutes in cell culture media and sulforhodamine B analysis was performed. Chorioallantoic membrane assay was conducted to define the new vessels formation behavior. The purity of collagen extracts was determined and showed two α-chains, i.e. the characteristic of type I collagen. Fourier transform infrared spectroscopy showed the characteristic peaks for amide I, I, III, and phosphate for collagen and composites. Scanning electron microscopy images showed three-dimensional mesh of collagen/apatite nano-fibers. Nontoxic behavior of composites was observed and there were graded and dose-related effects on experimental compounds. The angiogenesis and vessels formation behavior were observed in bioactive collagen composite. The obtained composites have potential to be used for tooth structure regeneration.