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Hepatocellular carcinoma (HCC), the most common type of liver cancer, is usually a latent and asymptomatic malignancy caused by different aetiologies, which is a result of various aberrant molecular heterogeneity and often diagnosed at advanced stages. The incidence and prevalence have significantly increased because of sedentary lifestyle, diabetes, chronic infection with hepatotropic viruses and exposure to aflatoxins. Due to advanced intra‐ or extrahepatic metastasis, recurrence is very common even after radical resection. In this paper, we highlighted novel therapeutic modalities, such as molecular‐targeted therapies, targeted radionuclide therapies and epigenetic modification‐based therapies. These topics are trending headlines and their combination with cell‐based immunotherapies, and gene therapy has provided promising prospects for the future of HCC treatment. Moreover, a comprehensive overview of current and advanced therapeutic approaches is discussed and the advantages and limitations of each strategy are described. Finally, very recent and approved novel combined therapies and their promising results in HCC treatment have been introduced.

Graphic abstract Limitations of monolayer culture conditions have motivated scientists to explore new models that can recapitulate the architecture and function of human organs more accurately. Recent advances in the improvement of protocols have resulted in establishing three-dimensional (3D) organ-like architectures called ‘organoids’ that can display the characteristics of their corresponding real organs, including morphological features, functional activities, and personalized responses to specific pathogens. We discuss different organoid-based 3D models herein, which are classified based on their original germinal layer. Studies of organoids simulating the complexity of real tissues could provide novel platforms and opportunities for generating practical knowledge along with preclinical studies, including drug screening, toxicology, and molecular pathophysiology of diseases. This paper also outlines the key challenges, advantages, and prospects of current organoid systems.

Recent developments in organoid culture technologies have made it possible to closely recapitulate intrinsic characteristics of different tissues under in vitro conditions. These organoids act as a translational bridge between the traditional 2D/3D cultures and the in vivo models for studying the tissue development processes, disease modeling, and drug screening. Matrigel and tissue-specific extracellular matrix have been shown to support organoid development, efficiently; however, their chemically undefined nature, non-tunable properties, and associated batch-to-batch variations often limit reproducibility of the assembly process. In this regard, chemically defined platforms offer wider opportunities to optimize and recreate tissue-specific microenvironment. The present review delineates the current research trends in this sphere, focusing on material perspective and the target tissues (e.g., neural, liver, pancreatic, renal, and intestinal). The review winds up with a discussion on the current limitations and future perspective to provide a basis for future research.

Conventional 2D intestinal models cannot precisely recapitulate biomimetic features in vitro and thus are unsuitable for various pharmacokinetic applications, development of disease models, and understanding the host-microbiome interactions. Thus, recently, efforts have been directed toward recreating in vitro models with intestine-associated unique 3D crypt-villus (for small intestine) or crypt-lumen (for large intestine) architectures. This review comprehensively delineates the current advancements in this research area in terms of the different microfabrication technologies (photolithography, laser ablation, and 3D bioprinting) employed and the physiological relevance of the obtained models in mimicking the features of native intestinal tissue. A major thrust of the manuscript is also on highlighting the dynamic interplay between intestinal cells (both the stem cells and differentiated ones) and different biophysical, biochemical, and mechanobiological cues along with interaction with other cell types and intestinal microbiome, providing goals for the future developments in this sphere. The article also manifests an outlook toward the application of induced pluripotent stem cells in the context of intestinal tissue models. On a concluding note, challenges and prospects for clinical translation of 3D patterned intestinal tissue models have been discussed.

Nature's material systems during evolution have developed the ability to respond and adapt to environmental stimuli through the generation of complex structures capable of varying their functions across direction, distances and time. 3D printing technologies can recapitulate structural motifs present in natural materials, and efforts are currently being made on the technological side to improve printing resolution, shape fidelity, and printing speed. However, an intrinsic limitation of this technology is that printed objects are static and thus inadequate to dynamically reshape when subjected to external stimuli. In recent years, this issue has been addressed with the design and precise deployment of smart materials that can undergo a programmed morphing in response to a stimulus. The term 4D printing was coined to indicate the combined use of additive manufacturing, smart materials, and careful design of appropriate geometries. In this review, we report the recent progress in the design and development of smart materials that are actuated by different stimuli and their exploitation within additive manufacturing to produce biomimetic structures with important repercussions in different but interrelated biomedical areas.

Metastasis is the leading cause of cancer mortality. Throughout the cascade of metastasis, cancer cells are exposed to both chemical and mechanical cues which influence their migratory behavior and survival. Mechanical forces in the milieu of cancer may arise due to excessive growth of cells in a confinement as in case of solid tumors, interstitial flows within tumors and due to blood flow in the vasculature as in case of circulating tumor cells. The focus of this review is to highlight the mechanical forces prevalent in the cancer microenvironment and discuss the impact of mechanical stresses on cancer progression, with special focus on mechanically induced autophagic response in cancer cells. Autophagy is a cellular homeostatic mechanism that a cell employs not only for recycling of damaged organelles and turnover of proteins involved in cellular migration but also as an adaptive response to survive through unfavourable stresses. Elucidation of the role of mechanically triggered autophagic response may lead to a better understanding of the mechanobiological aspects of metastatic cancer and unravelling the associated signaling mechanochemical pathways may hint at potential therapeutic targets.

The inert nature of most commercial polymers and nanomaterials results in limitations of applications in various industrial fields. This can be solved by surface modifications to improve physicochemical and biological properties, such as adhesion, printability, wetting and biocompatibility. Polymer functionalization allows to graft specific moieties and conjugate molecules that improve material performances. In the last decades, several approaches have been designed in the industry and academia to graft functional groups on surfaces. Here, we review surface decoration of polymers and nanomaterials, with focus on major industrial applications in the medical field, textile industry, water treatment and food packaging. We discuss the advantages and challenges of polymer functionalization. More knowledge is needed on the biology behind cell–polymer interactions, nanosafety and manufacturing at the industrial scale.

Background To study the immunomodulatory and protective role of dietary administered purified β-glucan obtained from edible mushroom (Pleurotus florida) in commercial broiler chicken, experimentally challenged with virulent Newcastle disease virus (NDV) on 7th day post treatment. Mushroom glucan (MG) at 15 mg/kg feed (group A) and MG at 30 mg/kg feed (group B) was administered to broiler birds for 20 days keeping control birds (group C) with a normal diet throughout. After 7 days post treatment, three groups of birds (n = 4, in each case) were challenged with virulent NDV. The immunological parameters were assessed to observe the protective efficacy of MG. Results When compared to the treatment regime, it was observed that in all the cases, group B birds showed higher immune-cellular and humoral responses in terms of enhanced immune-effector activities of blood leucocytes and intestinal intra-epithelial leucocytes and antibody production besides protection against NDV challenge than the others. After NDV challenge, 100% mortality was observed in control birds within 4 days, whereas in treated birds 50% and 75% protection of challenged birds was observed in group A and group B birds, respectively. The superoxide anion production by blood leucocytes of group A (0.641 ± 0.01) and group B (0.721 ± 0.01) birds were significantly higher than the control birds (0.283 ± 0.04) when assessed on 4th day post challenge. Group A (27.33 ± 1.20 μl and 25.33 ± 2.02 μl) and group B (33.66 ± 0.33 μl and 32.66 ± 0.33 μl) birds showed higher in vitro nitrite production by peripheral blood mononuclear cells (PBMC) and intestinal intra-epithelial leucocytes (iIEL), respectively, than the control (14.00 ± 0.57 μl and11 ± 0.57 μl) after challenge with virulent ND virus. In vitro lymphoproliferation (expressed as stimulation index) was significantly high in PBMC and iIEL of group A (0.371 ± 0.02 and 0.295 ± 0.02) and group B (0.428 ± 0.01 and 0.314 ± 0.01), respectively, than control (0.203 ± 0.01 and 0.135 ± 0.01) on 4th day of NDV challenge. The phagocytic activity of iIEL of the treated group birds showed higher values (24% and 32%) than the control group (14%). The haemagglutination inhibition (HI) titre was also observed higher in treated groups (group A, average HI titre 256, and group B, average HI titre 512) than control (HI titre, 32). Both groups (A&B) of birds were produced in vitro IFN-γ by PBMC and iIEL. Conclusion It is advisable to use 30 mg MG/kg feed in broiler birds to provide immunostimulation and for better output in terms of disease protection at least against ND virus.

The use of polymers and nanomaterials has vastly grown for industrial and biomedical sectors during last years. Before any designation or selection of polymers and their nanocomposites, it is vital to recognize the targeted applications which require these platforms to be modified. Surface functionalization to introduce the desired type and quantity of reactive functional groups to target a cell or tissue in human body is a pivotal approach to improve the physicochemical and biological properties of these materials. Herein, advances in the functionalized polymer and nanomaterials surfaces are highlighted along with their applications in biomedical fields, e.g., antimicrobial therapy and drug delivery.

The present study delineates the fabrication of paper-based devices for culturing liver cells and developing related bioassays. The devices were prepared by conventional lab-based LaserJet printing technology and employed for 3D cell culture. Our results demonstrated that the devices efficiently supported the growth of multiple cell types incuding HepG2, HUVEC, fibroblasts, and MSCs. We further showed that the device specifications (grade of paper or design parameters) greatly impacted the functional phenotype of the HepG2 cells. We also explored the application of the developed devices for routine cell culture, drug screening, coculture, and transwell migration assays. The cellular responses observed on the paper under different culture configurations were similar to those obtained in the case of tissue culture plate (TCP). Moreover, we showed that the paper-based devices were compatible with the immunocytochemistry and ELISA procedures (no indication of nonspecific matrix-antibody interaction). Considering the simplicity, experimental flexibility, cost-effectiveness, and multiplexibility of the paper-based liver models, it is deemed to be ideal for developing cell-based bioassays, especially in resource-limited settings.

Recent studies have shown that the utility of nanocarriers for the transportation of gaseous signalling molecules to their target site in a biological environment is an effective approach. In this work, we have developed for the first time visible light responsive nanocarriers for the effective release of H2S. Our newly developed nanocarriers for H2S release are constructed using two main ingredients: fluorescent carbon dots and quinoline as an H2S donor. The developed nanocarriers provided interesting properties like good solubility under physiological conditions, excellent fluorescence properties and efficient release ability of H2S with good quantum yield upon visible light irradiation. In vitro studies revealed that our designed nanocarriers exhibited abilities like efficient cellular internalization and good biocompatibility.

The present review provides a comprehensive outlook toward the possibilities of developing a functional in vitro liver tissue model on a paper platform. To this end, we first addressed the suitabil...

The lack of optimal physiological properties, bacterial colonization, and auto-osteoinduction, are the foremost issues of orthopedic implantations. In terms of bone healing, many researchers have reported the release of additional growth factors of the implanted biomaterials to accelerate the bone regeneration process. However, the additional growth factor may cause side effects such as contagion, nerve pain, and the formation of ectopic bone. Thus, the design of an osteoconductive scaffold having excellent biocompatibility, appropriate physicomechanical properties, and promoted auto osteoinductivity with antibacterial activity is greatly desired. In this study, 2D rodlike nanohydroxyapatite (nHA) adorned titanium phosphate (TP) with a flowerlike morphology was synthesized by a hydrothermal precipitation reaction. The nanohybrid material (nHA-TP) was incorporated into the synthesized polycaprolactone diol and spermine based thermoplastic polyurethane-urea (PUU) via in situ technique followed by salt leaching to fabricate the macroporous 3D polymer nanohybrid scaffold (PUU/nHA-TP). Structure explication of PUU was performed by NMR spectroscopy. The synthesized nanohybrid scaffold with 1% nHA-TP showed 67% increase of tensile strength and 18% improved modulus compared to the pristine PUU via formation of H-bonding or dative bonds between the metal and the amide linkage of the polyurethane or polyurea. In vitro study showing improved cell viability and proliferation of the seeded cell revealed the superior osteoconductivity of the nanohybrid scaffold. Most importantly, the in vivo experiments revealed a significant amount of bone regeneration in the nanohybrid scaffold implanted tibial site compared to the pristine scaffold without any toxic effect. Introduction of the minute amount of titanium phosphate within the adorned nHA promotes the osteoconductivity significantly by the capability of forming coordinate bonds of the titanium ion. Depending on the mechanical, physicochemical, in vitro characteristics, and in vivo osteoconductivity, the PUU/nHA-TP nanohybrid scaffold has great potential as an alternative biomaterial in bone tissue regeneration application.

3D printing technologies are rapidly revolutionizing all manufacturing sectors due to their ability to create objects with complex geometries in a reproducible and automated manner using material/cell-based formulations, precisely termed printing inks. In this regard, pectin, a naturally occurring plant polysaccharide, has been proposed as a potential component of ink formulations. In this mini-review, we overview the most recent advances made with pectin-based inks in the fields of tissue engineering and food manufacturing. We also discuss various strategies used to formulate 3D printable pectin inks. Finally, various challenges and prospects for future development are discussed.

Engineering constructs with adequate bioactive properties that could support effective repair/ regeneration of damaged tissues is still a persisting challenge. An effective and sustainable approach involving a combination of tissue engineering principles and herbal medicines could address this challenge. This particular domain has witnessed tremendous growth over the past decade. In this review, we provide an overview of engineered herbal constructs for tissue engineering applications. We have highlighted various properties of herbal medicines that are relevant to tissue repair and regeneration. Further, a discussion of different biomaterials, fabrication methods, and current progress made with herbal constructs has been provided. On a concluding note, challenges and outlook for further development and clinical translation of these herbal constructs have also been presented.

Extravasation of metastatic cells from the blood or lymphatic circulation and formation of secondary tumor at a distant site is a key step of cancer metastasis. In this study, we report the role of hemodynamic shear stresses in fostering the release of pro-extravasation factors through the mediation of autophagy in cervical cancer HeLa cells. HeLa cells were exposed to physiological shear stress through the microfluidic approach adapted in our previous study on the role of hemodynamic shear stresses in survival of HeLa cells. Herein, an optimum number of passes through a cylindrical microchannel was chosen such that the viability of cells was unaffected by shear. Shear-exposed cells were then probed for their invasive and migratory potential through in vitro migration and invasion assays. The dependence of cancer cells on mechanically-induced autophagy for extravasation was further assessed through protein expression studies. Our results suggest that shear stress upregulates autophagy, which fosters paxillin turnover thereby leading to enhanced focal adhesion disassembly and in turn enhanced cell migration. Concurrently, shear stress-induced secretion of pro-invasive factors like MMP-2 and IL-6 were found to be autophagy-dependent thereby hinting at autophagy as a potential therapeutic target in metastatic cancer. Proposed model for mechano-autophagic modulation of extravasation.

International audience; Excessive and unwarranted administration of antibiotics has invigorated the evolution of multidrug-resistant microbes. There is, therefore, an urgent need for advanced active compounds. Ionic liquids with short-lived ion-pair structures are highly tunable and have diverse applications. Apart from their unique physicochemical features, the newly discovered biological activities of ionic liquids have fascinated biochemists, microbiologists, and medical scientists. In particular, their antimicrobial properties have opened new vistas in overcoming the current challenges associated with combating antibiotic-resistant pathogens. Discussions regarding ionic liquid derivatives in monomeric and polymeric forms with antimicrobial activities are presented here. The antimicrobial mechanism of ionic liquids and parameters that affect their antimicrobial activities, such as chain length, cation/anion type, cation density, and polymerization, are considered. The potential applications of ionic liquids in the biomedical arena, including regenerative medicine, biosensing, and drug/biomolecule delivery, are presented to stimulate the scientific community to further improve the antimicrobial efficacy of ionic liquids.

A paradigm shift in conventional insulin delivery techniques is required to provide diabetic patients with painless, precise, safe and accurate insulin delivery solutions. Large size insulin molecules can be pushed through human skin layers by a micropump through hollow microneedles which provide a painless interphase to human skin. Ionic polymer metal composite membranes offer great advantages in micropump actuation due to their large deflections at relatively low actuation voltages. This makes them suitable to be implemented in insulin delivery devices. This article presents a novel integrated design of an insulin delivery device (IDD) consisting of a hollow microneedle array, drug reservoir and Nafion membrane actuation based micropump. To test the feasibility of the gold coated Nafion 115 membrane, it is utilized in the conventional circular as well as modified geometry having greater degree of freedom of movement by introducing cuts in membrane in a micropump structure and then implemented in the proposed IDD structure. The IDD achieves a DI water flowrate of $47.2~\mu $ L/min and Insulin flowrate of $44.8~\mu $ L/min for membrane with modified geometry which is higher as compared to the conventional membrane design. The device can achieve tunable insulin flowrate in the range of 20–45 $\mu $ L/min by varying the frequency (0.1-0.5Hz) and voltage (3-6V) paving way for its commercialization for painless insulin delivery. [2019-0109]

The present study delineates the preparation, characterization, and application of (3-Aminopropyl)triethoxysilane (APTES)/Caprine liver-derived extracellular matrix (CLECM) coated paper matrix for cell delivery. Here, we exploited positively charged surface of the paper matrix (as imparted by APTES derivatization) to improve the biological responses of the cells. Our results demonstrated that the functionalized paper matrixes favored the adhesion, growth, and proliferation of multiple cell types including normal, transformed, cancerous, and stem cells as compared to the pristine paper matrix. Upon implantation into the mice model, the developed paper matrix supported infiltration of the host cells and vasculature without showing any evidence of significant systemic toxicity. Moreover, the cells cultured on the paper matrix, when delivered to the CAM and mouse models, showed an enhanced vascular network around the substrate, thereby confirming its potential to deliver the cells in vivo. Together, the study confirms that the reported paper-based platform is easy to fabricate, cheap, portable and could efficiently be applied to cell delivery applications for either tissue repair or the development of humanized animal model.

This study aimed to identify the intracellular binding partner of a unique class of staphylococcal secreted exotoxins called superantigen-like proteins (SSL) from human macrophage and keratinocyte cell lysates. Here, we report that SSL1 specifically binds to human extracellular signal-regulated kinase 2 (hERK2), an important stress-activated kinase in mitogen-activated protein kinase signaling pathways. Western blot and in vitro binding studies with recombinant hERK2 confirmed the binding interaction of SSL1, SSL7, and SSL10 with hERK2. Moreover, the SSLs-hERK2 interaction was validated biochemically by ELISA. Our finding shows that SSLs play a novel role by binding with host cell MAP kinase signaling pathway protein. Understanding the SSL-hERK2 interaction will also provide a basis for designing SSL-based peptide inhibitors of hERK2 in cancer therapy.

Persulfides have been considered as potential signaling compounds similar to the H2S in "S-persulfidation", a sulfur-mediated redox cycle. The research of this sulfur-mediated species is hindered because of the lack of efficient persulfide donors. In this current study, we have developed one- and two-photon-activated persulfide donors based on an o-nitrobenzyl (ONB) phototrigger, which releases the biologically active persulfide (N-acetyl l-cysteine persulfide, NAC-SSH) in a spatiotemporal manner. Next, we have demonstrated the detection of persulfide release both qualitatively and quantitatively using the well-known "turn on" fluorescence probe, that is, monobromobimane, and the trapping agent, that is, 2,4-dinitrofluorobenzene, respectively. Furthermore, we examined the cytotoxicity of synthesized persulfide donors on HeLa cells and the cytoprotective ability in the highly oxidizing cellular environment.

Metastasis remains the primary cause of cancer mortality. Throughout the process of metastasis, cancer cells experience mechanical forces, which may turn out to be the key towards their migratory, homeostatic and survival characteristics. However, the influence of compressive stress on the underlying mechanism of cancer cell adaptation during metastasis has remained grossly unexplored. In this study, we have investigated whether compressive force induces autophagy in HeLa cells with potential implications in cellular invasiveness. To this end, we have adopted a simple strategy to create the mechanically-compressed tumor microenvironment, in vitro, by applying appropriate compression to agarose-scaffolded HeLa cell-encapsulated alginate beads. Our findings confirm that compression upregulates autophagy, which promotes paxillin turnover and active MMP-2 secretion, leading to enhanced migration of HeLa cells. We further show that autophagy induction by compression is affected by the phosphorylation of p38 MAPKs, a process that is mediated by intact membrane lipid rafts. Identifying the role of such mechanically triggered cellular responses, guiding crucial processes like cell migration, may lead to better understanding of the mechanobiological aspects of metastatic cancer and unveil potential therapeutic targets.

Liver tissue engineering aims at the possibility of reproducing a fully functional organ for the treatment of acute and chronic liver disorders. Approaches in this field endeavor to replace organ transplantation (gold standard treatment for liver diseases in a clinical setting) with in vitro developed liver tissue constructs. However, the complexity of the liver microarchitecture and functionality along with the limited supply of cellular components of the liver pose numerous challenges. This review provides a comprehensive outlook onto how the physicochemical, mechanobiological, and spatiotemporal aspects of the substrates could be tuned to address current challenges in the field. We also highlight the strategic advancements made in the field so far for the development of artificial liver tissue. We further showcase the currently available prototypes in research and clinical trials, which shows the hope for the future of liver tissue engineering.

Plant lectins are non-immunoglobin in nature and bind to the carbohydrate moiety of the glycoconjugates without altering any of the recognized glycosyl ligands. Plant lectins have found applications as cancer biomarkers for recognizing the malignant tumor cells for the diagnosis and prognosis of cancer. Interestingly, plant lectins contribute to inducing cell death through autophagy and apoptosis, indicating their potential implication in cancer inhibitory mechanism. In the present review, anticancer activities of major plant lectins have been documented, with a detailed focus on the signaling circuit for the possible molecular targeted cancer therapy. In this context, several lectins have exhibited preclinical and clinical significance, driving toward therapeutic potential in cancer treatment. Moreover, several plant lectins induce immunomodulatory activities, and therefore, novel strategies have been established from preclinical and clinical investigations for the development of combinatorial treatment consisting of immunotherapy along with other anticancer therapies. Although the application of plant lectins in cancer is still in very preliminary stage, advanced high-throughput technology could pave the way for the development of lectin-based complimentary medicine for cancer treatment.

The development of a pre-vascularized liver tissue construct with native-like 3-dimensional (3D) microarchitecture and extracellular matrix (ECM) composition is essential to meet the current demand for liver transplantation. Here, we report the methodology and in-depth characterization of the decellularized caprine liver scaffold (CLECM-S) for tissue engineering application. CLECM-S retained crucial ECM components and structural features similar to the native liver tissue. For comparative evaluation, conventional glutaraldehyde crosslinked collagen scaffold (Col-S) was taken as a control. CLECM-S underwent a slow but sustained swelling and collagenase mediated degradation and had the mechanical stiffness closer to that of the native human liver. HepG2 cells cultured on CLECM-S exhibited an enhanced expression of mature and functional hepatocyte markers. In addition, CLECM-S also showed pro-angiogenic properties as confirmed by Chick Chorioallantoic Membrane (CAM) assay. Upon implantation in a mouse model, the scaffolds did not elicit any significant immunogenic response. These results, together, provide a solid evidence depicting superiority of CLECM-S over conventional Col-S for liver tissue engineering applications.

In view of many promising applications of gold nanoclusters (AuNCs), nanothermometry is an important field of research in biology and medicine. Here, we demonstrate the temperature dependent photophysical properties of highly luminescent green emitting 6-aza-2-thiothymine/l-arginine-stabilized Au nanosclusters (ATT/Arg Au NCs) by using steady state and time-resolved photoluminescence spectroscopy. Significantly, thermoresponsive properties of these highly photostable and biocompatible Au NCs are reversible, which endow the probe for further bioanalytical applications with great prospects. Additionally, protein-NC interaction mechanism has been elucidated in vitro and in vivo that dictates the complex behavior of the NCs with living organisms. These ultrasmall Au NCs are observed to accumulate in the cellular cytoplasm by translocating through the membrane as evidenced from the confocal laser scanning microscopy (CLSM). In vivo temperature sensing examined with human osteosarcoma cell line (MG-63 cell) by employing fluorescence lifetime imaging microscopy (FLIM) technique reveals the optimistic application of these lifetime-based nanosensors in biomedicine and biotechnology.

Intrauterine Contraceptive Devices with multifaceted application potential is a need of an hour. Although, copper-based IUDs exert an effective contraceptive as well as anticancer effects in a long-term basis, but also results in multiple complications. In this regard, RISUG® a polymer based contraceptive device has been introduced as a suitable alternative. However, its potential to impart protective effects against development of endometrial cancer still remains unexplored. This article presents the hypothesis on this unexplored domain and provides scientific facts to support the hypothesis. The mechanism of anticancerous activity is hypothesized that RISUG® involves its lipid membrane destabilizing activity. This activity is modulated by both, the cellular microenvironment and lipid bilayer composition. Acidic environment along with the significantly higher fluidic nature of lipid bilayer of the cancerous cells make them more prone to lipid solubilisation effect of RISUG®. We here present an in-depth insight into the factors that would favour faster solubilisation of cancer cell membrane, thereby exerting an anticancer effect.

We have elucidated the role of unsaturated fatty acid in the in vitro model phospholipid membrane and in vivo live cell membrane. Fluorescence microscopy and time-resolved fluorescence spectroscopy have been employed to uncover how modulation of vesicle bilayer fluidity persuades structural transformation. This unsaturation induced structural transformation due to packing disorder in bilayer has been delineated through spatially resolved fluorescence lifetime imaging microscopy (FLIM) and fluorescence polarization or anisotropy imaging microscopy (FPIM/FAIM). Structure-function relationship of phospholipid vesicle is also investigated by monitoring intervesicular water dynamics behavior, which has been demonstrated by temporally resolved fluorescence spectroscopy (TRFS) techniques. Nevertheless, it has also been manifested from this study that loss of rigidity in bilayer breaks down the strong hydrogen bond (H-bond) network around the charged lipid head groups. The disruption of this H-bond network increases the bilayer elasticity, which helps to evolve various kinds of vesicular structure. Furthermore, the significant influence of unsaturated fatty acid on membrane bilayer has been ratified through in vivo live cell imaging.

Background Epithelial-to-mesenchymal transition (EMT), a key step in oral cancer progression, is associated with invasion, metastasis, and therapy resistance, thus targeting the EMT represents a critical therapeutic strategy for the treatment of oral cancer metastasis. Our previous study showed that Abrus agglutinin (AGG), a plant lectin, induces both intrinsic and extrinsic apoptosis to activate the tumor inhibitory mechanism. Objective This study aimed to investigate the role of AGG in modulating invasiveness and stemness through EMT inhibition for the development of antineoplastic agents against oral cancer. Methods The EMT- and stemness-related proteins were studied in oral cancer cells using Western blot analysis and fluorescence microscopy. The potential mechanisms of Snail downregulation through p73 activation in FaDu cells were evaluated using Western blot analysis, immunoprecipitation, confocal microscopy, and molecular docking analysis. Immunohistochemical staining of the tumor samples of AGG-treated FaDu-xenografted nude mice was performed. Results At the molecular level, AGG-induced p73 suppressed Snail expression, leading to EMT inhibition in FaDu cells. Notably, AGG promoted the translocation of Snail from the nucleus to the cytoplasm in FaDu cells and triggered its degradation through ubiquitination. In this setting, AGG inhibited the interaction between Snail and p73 in FaDu cells, resulting in p73 activation and EMT inhibition. Moreover, in epidermal growth factor (EGF)-stimulated FaDu cells, AGG abolished the upregulation of extracellular signal-regulated kinase (ERK)1/2 that plays a pivotal role in the upregulation of Snail to regulate the EMT phenotypes. In immunohistochemistry analysis, FaDu xenografts from AGG-treated mice showed decreased expression of Snail, SOX2, and vimentin and increased expression of p73 and E-cadherin compared with the control group, confirming EMT inhibition as part of its anticancer efficacy against oral cancer. Conclusion In summary, AGG stimulates p73 in restricting EGF-induced EMT, invasiveness, and stemness by inhibiting the ERK/Snail pathway to facilitate the development of alternative therapeutics for oral cancer.

We have utilized an m-amino benzyl based photoremovable protecting group (PRPG) to develop a new water soluble H2S donor. It efficiently releases H2S on demand in a spatio-temporally controlled fashion by an excited state "meta effect" with good chemical and photochemical quantum yield in an aqueous environment. The efficient photorelease of H2S under physiological conditions was also demonstrated by in vitro studies.

Lack of auto osteogenesis and clinical complexities of repairing of bone after severe injuries, urge to develop a significant approach to promote regeneration of bone. The present work represents ornamentation of 2D rod-like nanohydroxyapatite (nHA) on ultra-low concentration graphene oxide (GO) sheet. The nanohybrids (GO-nHA) were incorporated into the spermine based high strength thermoplastic polyurethane-urea (PUU) matrices by in situ technique and the porous scaffolds were fabricated. 1 wt% GO-nHA filled scaffold displayed dramatically improved physico-mechanical properties. Cytotoxicity study using osteoblast cell like MG-63 cell line revealed positive cell viability (above 95%) and increased proliferation over a period of 14 days of culture. Semi-quantitative Real Time polymerase Chain Reaction (qRT-PCR) showed positive expression of collagen type I and osteocalcin indicating excellent maturation and biomineralization of osteoblasts. To avoid burden of carbonaceous particulate in body, very low percentage of GO (0.15%) was incorporated into the scaffold to improve mechanical properties, surface wettability, cell viability and cell proliferation drastically. Furthermore, in vivo study confirmed the promoted osteogenesis of PUU/GO-nHA scaffold in vivo without any cytotoxicity. Based on mechanical, in vitro and in vivo study the high strength nanohybrid scaffold exhibited tremendous potential for orthopedic applications.

A water-soluble dilithium salt BODIPY derivative (LiBDP) with appended dicarboxylate pseudo-crown ether [NO4] coordinating sites has been designed, synthesized and characterized successfully for the selective and sensitive recognition of Cd2+ in aqueous media. The chemosensor exhibits a remarkable increase in fluorescence intensity as well as a distinct color change upon the addition of Cd2+ over other environmentally and biologically relevant metal ions in H2O. The fluorometric response of LiBDP is attributed to the metal chelation-enhanced fluorescence (MCHEF) effect which has been confirmed by a strong association constant of 2.57 ± 1.06 × 105 M−1 and Job's plot, indicating 1 : 1 binding stoichiometry between LiBDP and Cd2+. Frontier molecular orbital analysis (obtained from DFT studies) also illustrates the turn-on fluorescence of the probe by blocking photoinduced electron transfer (PET) after coordination to Cd2+. The probe can detect Cd2+ in a competitive environment up to a submicromolar level in a biologically significant pH range. The sensor is proved to be reversible and reusable by the alternative addition of Cd2+ followed by S2−. The OFF/ON/OFF sensing behavior is utilized to construct an INHIBIT molecular logic gate based on the two inputs of Cd2+ and S2− and a fluorescence intensity at 512 nm as an output. The test paper experiment demonstrates the practical utility of LiBDP to monitor Cd2+ in an aqueous sample. Finally, the sensing probe was utilized to monitor Cd2+ in living cells.

A series of spherical magneto-responsive nanogels were fabricated by formulating different sets of star block copolymers based on pentaerythritol–poly(e-caprolactone)-b-poly(acrylic acid) (PE–PCL-b-PAA) combined with amine-functionalized magnetic nanoparticles for targeted cancer therapy. Superparamagnetic nanoparticles, Fe3O4 (5 ± 0.5 nm), were modified with (3-aminopropyl)trimethoxysilane to introduce the amine functionality into the system which also imparts colloidal stability. In the star block copolymer, the hydrophilic PAA chain length has an architecture such that it can accommodate a large number of amine-functionalized magnetic nanoparticles. The hydrodynamic size of the nanogel has been observed in the range of 65 ± 2 nm to 616 ± 7 nm. The as-prepared nanogel has been employed to deliver an anticancer drug, doxorubicin (DOX). A maximum of 20% of DOX encapsulation has been observed. In the presence of physiological pH of cancer cells (pH 5), the nanogel is able to deliver 73% of drug in 24 h which is further enhanced in the presence of an external static magnetic field (76% release). Under the influence of a high-frequency alternating magnetic field the in vitro drug release rate is 56% h−1. The low viscosity (0.21 Pa s) at high shear rate (1000 s−1) makes the nanogel suitable for painless injection. The pristine nanogel shows about 80% cell viability against the C6 glioma cell line. The magnetic field-induced targeting effect (cell uptake) of the fabricated nanogel has been visualized by fluorescence confocal microscopy. The therapeutic effect of the DOX-loaded nanogel has been examined against the C6 glioma cell line and it is found that the DOX-loaded magnetic nanogel having a composition of PE–PCL20-b-PAA180 with 10% amine-modified Fe3O4 shows selectively high toxic (IC50 = 3.85 μg mL−1) effect towards the C6 glioma cell line. This kind of new class of magnetic nanogel can open a new direction for MRI-guided drug delivery systems.

Adequate oxygen tension has been associated with better tissue regeneration and reversal of tumor cells' resistance against various therapeutic modalities. Over the past two decades, an enormous amount of efforts have been made to develop strategies and materials that could actively generate oxygen to contrast local hypoxia at injury or tumor site. In this context, the current research trend is exploring photosynthetic microorganisms as a continuous oxygenation source. This concise review provides a brief overview of recent developments made with photosynthetic microbes, ascertaining their therapeutic capabilities in tissue engineering and anticancer therapy.

Escherichia coli low-molecular-mass (LMM) Penicillin-binding proteins (PBPs) help in hydrolysing the peptidoglycan fragments from their cell wall and recycling them back into the growing peptidoglycan matrix, in addition to their reported involvement in biofilm formation. Biofilms are external slime layers of extra-polymeric substances that sessile bacterial cells secrete to form a habitable niche for themselves. Here, we hypothesize the involvement of Escherichia coli LMM PBPs in regulating the nature of exopolysaccharides (EPS) prevailing in its extra-polymeric substances during biofilm formation. Therefore, this study includes the assessment of physiological characteristics of E. coli CS109 LMM PBP deletion mutants to address biofilm formation abilities, viability and surface adhesion. Finally, EPS from parent CS109 and its ΔPBP4 and ΔPBP5 mutants were purified and analysed for sugars present. Deletions of LMM PBP reduced biofilm formation, bacterial adhesion and their viability in biofilms. Deletions also diminished EPS production by ΔPBP4 and ΔPBP5 mutants, purification of which suggested an increased overall negative charge compared with their parent. Also, EPS analyses from both mutants revealed the appearance of an unusual sugar, xylose, that was absent in CS109. Accordingly, the reason for reduced biofilm formation in LMM PBP mutants may be speculated as the subsequent production of xylitol and a hindrance in the standard flow of the pentose phosphate pathway.