Nanotherapeutic approaches for delivery of long non-coding RNAs: an updated review with emphasis on cancer.

The long noncoding RNAs (lncRNAs) comprise a wide range of RNA species whose length exceeds 200 nucleotides, which regulate the expression of genes and cellular functions in a wide range of organisms. Several diseases, including malignancy, have been associated with lncRNA dysregulation. Due to their functions in cancer development and progression, lncRNAs have emerged as promising biomarkers and therapeutic targets in cancer diagnosis and treatment. Several studies have investigated the anti-cancer properties of lncRNAs; however, only a few lncRNAs have been found to exhibit tumor suppressor properties. Furthermore, their length and poor stability make them difficult to synthesize. Thus, to overcome the instability of lncRNAs, poor specificity, and their off-target effects, researchers have constructed nanocarriers that encapsulate lncRNAs. Recently, translational medicine research has focused on delivering lncRNAs into tumor cells, including cancer cells, through nano-drug delivery systems in vivo. The developed nanocarriers can protect, target, and release lncRNAs under controlled conditions without appreciable adverse effects. To deliver lncRNAs to cancer cells, various nanocarriers, such as exosomes, microbubbles, polymer nanoparticles, 1,2-dioleyl-3-trimethylammoniumpropane chloride nanocarriers, and virus-like particles, have been successfully developed. Despite this, every nanocarrier has its own advantages and disadvantages when it comes to delivering nucleic acids effectively and safely. This article examines the current status of nanocarriers for lncRNA delivery in cancer therapy, focusing on their potential to enhance cancer treatment.

Corrigendum: Fabrication and evaluation of herbal beads to slow cell ageing.

[This corrects the article DOI: 10.3389/fbioe.2022.1025405.].

Nano-biochar: recent progress, challenges, and opportunities for sustainable environmental remediation.

Biochar is a carbonaceous by-product of lignocellulosic biomass developed by various thermochemical processes. Biochar can be transformed into "nano-biochar" by size reduction to nano-meters level. Nano-biochar presents remarkable physico-chemical behavior in comparison to macro-biochar including; higher stability, unique nanostructure, higher catalytic ability, larger specific surface area, higher porosity, improved surface functionality, and surface active sites. Nano-biochar efficiently regulates the transport and absorption of vital micro-and macro-nutrients, in addition to toxic contaminants (heavy metals, pesticides, antibiotics). However an extensive understanding of the recent nano-biochar studies is essential for large scale implementations, including development, physico-chemical properties and targeted use. Nano-biochar toxicity on different organisms and its in-direct effect on humans is an important issue of concern and needs to be extensively evaluated for large scale applications. This review provides a detailed insight on nanobiochar research for (1) development methodologies, (2) compositions and properties, (3) characterization methods, (4) potentiality as emerging sorbent, photocatalyst, enzyme carrier for environmental application, and (5) environmental concerns.

A critical review on therapeutic approaches of CRISPR-Cas9 in diabetes mellitus.

Diabetes mellitus (D.M.) is a common metabolic disorder caused mainly by combining two primary factors, which are (1) defects in insulin production by the pancreatic ß-cells and (2) responsiveness of insulin-sensitive tissues towards insulin. Despite the rapid advancement in medicine to suppress elevated blood glucose levels (hyperglycemia) and insulin resistance associated with this hazard, a demand has undoubtedly emerged to find more effective and curative dimensions in therapeutic approaches against D.M. The administration of diabetes treatment that emphasizes insulin production and sensitivity may result in unfavorable side effects, reduced adherence, and potential treatment ineffectiveness. Recent progressions in genome editing technologies, for instance, in zinc-finger nucleases, transcription activator-like effector nucleases, and clustered regularly interspaced short palindromic repeat (CRISPR-Cas)-associated nucleases, have greatly influenced the gene editing technology from concepts to clinical practices. Improvements in genome editing technologies have also opened up the possibility to target and modify specific genome sequences in a cell directly. CRISPR/Cas9 has proven effective in utilizing ex vivo gene editing in embryonic stem cells and stem cells derived from patients. This application has facilitated the exploration of pancreatic beta-cell development and function. Furthermore, CRISPR/Cas9 enables the creation of innovative animal models for diabetes and assesses the effectiveness of different therapeutic strategies in treating the condition. We, therefore, present a critical review of the therapeutic approaches of the genome editing tool CRISPR-Cas9 in treating D.M., discussing the challenges and limitations of implementing this technology.

Ebola Virus Disease Vaccines: Development, Current Perspectives & Challenges.

The global outgoing outbreaks of Ebola virus disease (EVD) in different regions of Sudan, Uganda, and Western Africa have brought into focus the inadequacies and restrictions of pre-designed vaccines for use in the battle against EVD, which has affirmed the urgent need for the development of a systematic protocol to produce Ebola vaccines prior to an outbreak. There are several vaccines available being developed by preclinical trials and human-based clinical trials. The group of vaccines includes virus-like particle-based vaccines, DNA-based vaccines, whole virus recombinant vaccines, incompetent replication originated vaccines, and competent replication vaccines. The limitations and challenges faced in the development of Ebola vaccines are the selection of immunogenic, rapid-responsive, cross-protective immunity-based vaccinations with assurances of prolonged protection. Another issue for the manufacturing and distribution of vaccines involves post authorization, licensing, and surveillance to ensure a vaccine's efficacy towards combating the Ebola outbreak. The current review focuses on the development process, the current perspective on the development of an Ebola vaccine, and future challenges for combatting future emerging Ebola infectious disease.

Exploring Microbial-Based Green Nanobiotechnology for Wastewater Remediation: A Sustainable Strategy.

Water scarcity due to contamination of water resources with different inorganic and organic contaminants is one of the foremost global concerns. It is due to rapid industrialization, fast urbanization, and the low efficiency of traditional wastewater treatment strategies. Conventional water treatment strategies, including chemical precipitation, membrane filtration, coagulation, ion exchange, solvent extraction, adsorption, and photolysis, are based on adopting various nanomaterials (NMs) with a high surface area, including carbon NMs, polymers, metals-based, and metal oxides. However, significant bottlenecks are toxicity, cost, secondary contamination, size and space constraints, energy efficiency, prolonged time consumption, output efficiency, and scalability. On the contrary, green NMs fabricated using microorganisms emerge as cost-effective, eco-friendly, sustainable, safe, and efficient substitutes for these traditional strategies. This review summarizes the state-of-the-art microbial-assisted green NMs and strategies including microbial cells, magnetotactic bacteria (MTB), bio-augmentation and integrated bioreactors for removing an extensive range of water contaminants addressing the challenges associated with traditional strategies. Furthermore, a comparative analysis of the efficacies of microbe-assisted green NM-based water remediation strategy with the traditional practices in light of crucial factors like reusability, regeneration, removal efficiency, and adsorption capacity has been presented. The associated challenges, their alternate solutions, and the cutting-edge prospects of microbial-assisted green nanobiotechnology with the integration of advanced tools including internet-of-nano-things, cloud computing, and artificial intelligence have been discussed. This review opens a new window to assist future research dedicated to sustainable and green nanobiotechnology-based strategies for environmental remediation applications.

A Bioengineered Quercetin-Loaded 3D Bio-Polymeric Graft for Tissue Regeneration and Repair.

Phytochemicals extracted from plant sources have potential remedial effects to cure a broad range of acute to severe illnesses and ailments. Quercetin is a flavonoid isolated from different dietary sources such as vegetables and fruits, exhibiting strong anti-inflammatory, anti-oxidative and non-toxic effects on the biological system. However, the direct uptake or administration of quercetin results in loss of functionality, poor activity, and reduced shelf-life of the bioactive component. In this regard, to improve the uptake, potential, and efficiency of natural components with prolonged storage in the host's body after administration, numerous polymer drug delivery systems have been created. In the current study, three-dimensional (3D) porous (porosity: 92%; pore size: 81 µm) bio-polymeric foaming gelatin-alginate (GA) beads were fabricated for the entrapment of quercetin as therapeutic drug molecules-gelatin-alginate-quercetin (GAQ). The GAQ beads showed a significant uptake of quercetin molecules resulting in a reduction of reduced porosity up to 64% and pore size 63 µm with a controlled release profile in the PBS medium, showing ~80% release within 24 h. Subsequently, the GAQ beads showed remarkable antioxidant effects, and 95% anti-inflammatory activities along with remarkable in vitro cell culture growth and the observed proliferation of seeded fibroblast cells. Thus, we can conclude that the consistent release of quercetin showed non-toxic effects on normal cell lines and the bioactive surface of the GAQ beads enhances cell adhesion, proliferation, and differentiation more effectively than control GA polymeric beads and tissue culture plates (TCP). In summary, these findings show that these GAQ beads act as a biocompatible 3D construct with enormous potential in medicinal administration and tissue regeneration for accelerated healing.

Fabrication and evaluation of herbal beads to slow cell ageing.

Several therapies and cosmetics are available commercially to prevent or delay cell ageing, which manifests as premature cell death and skin dullness. Use of herbal products such as Aloe vera, curcumin, vitamin C-enriched natural antioxidant, and anti-inflammatory biomolecules are potential ways to prevent or delay ageing. Eggshell membrane (ESM) is also a rich source of collagen; glycosaminoglycans (GAGs) also play an essential role in healing and preventing ageing. It is important to use an extended therapeutic process to prolong the effectiveness of these products, despite the fact that they all have significant anti-ageing properties and the ability to regenerate healthy cells. Encapsulated herbal components are therefore designed to overcome the challenge of ensuring continued treatment over time to prolong the effects of a bioactive component after in situ administration. To study their synergistic effects on a cellular level, alginate, Aloe vera, and orange peel extract were encapsulated in bio-polymeric foaming beads and modified with eggshell membrane protein (ESMP) at various concentrations (1 gm, 2 gm, and 5 gm): (A-Av-OP, A-Av-OP-ESMP1, ESMP2, and ESMP3). Analysis of the structural and functional properties of foaming beads showed interconnected 3D porous structure, a surface-functionalized group for entrapment of ESMP, and a significant reduction in pore size (51-35 m) and porosity (80%-60%). By performing DPPH assays, HRBC stabilization assays, and antibacterial tests, the beads were assessed as a natural anti-ageing product with sustained release of molecules effective against inflammatory response, oxidative stress, and microbial contamination. MTT assays were conducted using in vitro cell cultures to demonstrate cytocompatibility (in mouse 3T3 fibroblast cells) and cytotoxicity (in human carcinoma HeLa cells). Our study demonstrates that bio-polymeric ESMP beads up to 2 g (A-Av-OP-ESMP2) are practical and feasible natural remedies for suspending defective cell pathways, preventing cell ageing, and promoting healthy cell growth, resulting in a viable and practical natural remedy or therapeutic system.

The emergence of metal oxide nanoparticles (NPs) as a phytomedicine: A two-facet role in plant growth, nano-toxicity and anti-phyto-microbial activity.

Anti-microbial resistance (AMR) has recently emerged as an area of high interest owing to the rapid surge of AMR phenotypes. Metal oxide NPs (MeONPs) have been identified as novel phytomedicine and have recently peaked a lot of interest due to their potential applications in combating phytopathogens, besides enhancing plant growth and yields. Numerous MeONPs (Ti2O, MgO, CuO, Ag2O, SiO2, ZnO, and CaO) have been synthesized and tested to validate their antimicrobial roles without causing toxicity to the cells. This review discusses the application of the MeONPs with special emphasis on anti-microbial activities in agriculture and enlists how cellular toxicity caused through reactive oxygen species (ROS) production affects plant growth, morphology, and viability. This review further highlights the two-facet role of silver and copper oxide NPs including their anti-microbial applications and toxicities. Furthermore, the factor modulating nanotoxicity and immunomodulation for cytokine production has also been discussed. Thus, this article will not only provide the researchers with the potential bottlenecks but also emphasizes a comprehensive outline of breakthroughs in the applicability of MeONPs in agriculture.

Governing HPV-related carcinoma using vaccines: Bottlenecks and breakthroughs.

Human papillomavirus (HPV) contributes to sexually transmitted infection, which is primarily associated with pre-cancerous and cancerous lesions in both men and women and is among the neglected cancerous infections in the world. At global level, two-, four-, and nine-valent pure L1 protein encompassed vaccines in targeting high-risk HPV strains using recombinant DNA technology are available. Therapeutic vaccines are produced by early and late oncoproteins that impart superior cell immunity to preventive vaccines that are under investigation. In the current review, we have not only discussed the clinical significance and importance of both preventive and therapeutic vaccines but also highlighted their dosage and mode of administration. This review is novel in its way and will pave the way for researchers to address the challenges posed by HPV-based vaccines at the present time.

Biomedical grafts for tracheal tissue repairing and regeneration "Tracheal tissue engineering: an overview".

Airway system is a vital part of the living being body. Trachea is the upper respiratory portion that connects nostril and lungs and has multiple functions such as breathing and entrapment of dust/pathogen particles. Tracheal reconstruction by artificial prosthesis, stents, and grafts are performed clinically for the repairing of damaged tissue. Although these (above-mentioned) methods repair the damaged parts, they have limited applicability like small area wounds and lack of functional tissue regeneration. Tissue engineering helps to overcome the above-mentioned problems by modifying the traditional used stents and grafts, not only repair but also regenerate the damaged area to functional tissue. Bioengineered tracheal replacements are biocompatible, nontoxic, porous, and having 3D biomimetic ultrastructure with good mechanical strength, which results in faster and better tissue regeneration. Till date, the bioengineered tracheal replacements studies have been going on preclinical and clinical levels. Besides that, still many researchers are working at advance level to make extracellular matrix-based acellular, 3D printed, cell-seeded grafts including living cells to overcome the demand of tissue or organ and making the ready to use tracheal reconstructs for clinical application. Thus, in this review, we summarized the tracheal tissue engineering aspects and their outcomes.

Silk fibroin protein modified acellular dermal matrix for tissue repairing and regeneration.

Worldwide the demand of skin-graft has been increasing day by day, for these different biomaterials and techniques have been used. In the present study, we have fabricated Silk Fibroin (SF) modified hybrid acellular goat-dermal matrix (SF-AGDM) by modifying the AGDM in different concentration SF- 5, 10, 15%, for enhancing the wound healing process. The grafts (AGDM and SF-AGDM) were evaluated for skin tissue regeneration by subjecting it through physical, chemical and biological characterization. SLS analysis showed the molecular weight of SF was 10,000 Da. Here, we found that SF-AGDM modified with low concentration of SF showed good porosity 78.56 ±â€¯14.30% and pore size 74.69 ±â€¯28.66 µm as similar to the AGDM. FTIR analysis showed the shifting of NH stretching (3400-3600 cm-1), amide I band at 3427 cm-1 and 1641 cm-1 and disappearance of the peaks of CH asymmetrical stretching (3000-2800 cm-1), amide II and amide III band, which indicate formation of amide linkage or other interaction between the SF protein and AGDM. In vitro cell culture studies by seeding 3 T3 mouse fibroblast cells on the scaffold revealed excellent cell viability, proliferation rate and adhesion in the scaffold. Pre-clinical study done in albino mice model showed within 14 days, all the wounds were completely cured, full thickness skin was regenerated without any significant inflammatory response. SF-ADGM results better healing as compared to the unmodified AGDM, which indicates the synergetic effect of SF coupled with acellular ECM based matrix. Thus, SF-AGDM is biocompatible, cost-effective material that can be potentially applied for tissue engineering application.

Erratum to: Decellularization Methods for Scaffold Fabrication.

The publisher regrets that an author was not mentioned in the chapter by mistake. The details of the author are provided below:Archna Dhasmana - Department of Polymer and Process Engineering, Indian Institute of Technology, Roorkee, India.

Decellularization Methods for Scaffold Fabrication.

Decellularization is the process of removal of native cells from tissue, leaving behind a three-dimensional (3D) ultrastructure of extracellular matrix (ECM) proteins while preserving the bioactivity and mechanics of the tissue. It offers a unique top-down approach for fabricating ECM based natural scaffold for tissue engineering application. Herein, this chapter presents the fabrication of decellularized scaffold employing different methods: whole organ perfusion, immersion and agitation, pressure gradient, and supercritical fluid. The decellularized scaffold aims to exploit the nature-designed 3D architecture, a successful platform technology, for creating scaffolding materials for tissue engineering and regenerative medicine.