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The development of effective carriers enabling combination cancer therapy is of practical importance due to its potential to enhance the effectiveness of cancer treatment. However, most of the reported carriers are monofunctional in nature. The carriers that can be applied to concomitantly mediate multiple treatment modalities are highly deficient. This study fills this gap by reporting the design and fabrication of ROS-generating carbohydrate-based pH-responsive beads with intrinsic anticancer therapy and multidrug co-delivery capacity for combination cancer therapy. Sodium alginate (SA) microspheres and reduced graphene oxide (rGO)-embedded chitosan (CS) beads are developed via emulsion-templated ionic gelation for a combination therapy involving co-delivery of curcumin (CUR) and 5-fluororacil (5-FU). Drug-encapsulated microbeads are characterized by FTIR, DSC, TGA, XRD, and SEM. 5-FU and CUR-encapsulated microbeads are subjected to

Intravesical chemotherapy is generally used in the clinic for treating bladder cancer (BCa), but its efficacy is limited due to the permeation barrier and side effects caused by the off-targeting of normal urothelial cells. In this study, BCa cell-derived membrane nanovesicles were used as drug carriers, and their homologous tumor-targeting capacity was utilized. A BCa-targeting hendeca-arginine peptide was functionalized onto the nanovesicles to impart a mucus-penetrating ability and thus overcome the permeation barrier. The tumor-targeting and mucus-penetrating nanovesicles were stable in urine, were highly permeable to the glycosaminoglycan layer, and specifically targeted BCa. The vesicles were internalized through caveolin-mediated endocytosis, were transported to nonlysosome-localized intracellular regions, and efficiently infiltrated bladder tumor spheroids. In in vivo intravesical chemotherapy, the nanovesicles achieved chemo-resection in murine orthotopic BCa models. This BCa-targeting and mucus-penetrating drug delivery system may be promising for the intravesical chemotherapy of BCa.

Pu Zhang1 *, Haibao Zhang2 *, Bin Zheng1 *, Heng Wang,1 Xiaolong Qi,1 Shuai Wang,1 Zhenghong Liu,1 Li Sun,1 Yang Liu,3 Xiaowen Qin,1 Weijiao Fan,1 Minghai Ma,2 Wing-Fu Lai,1 Dahong Zhang1 1Urology & Nephrology Center, Department of Urology, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang People’s Republic of China; 2Key Laboratory of Environment and Genes Related to Diseases, Xi’an Jiaotong University, Xi’an, People’s Republic of China; 3Cancer Center, Department of Ultrasound Medicine, Zhejiang Provincial People’s Hospital, Affiliated People’s Hospital, Hangzhou Medical College, Hangzhou, Zhejiang People’s Republic of China*These authors contributed equally to this workCorrespondence: Dahong Zhang; Wing-Fu Lai, No. 138 Shang Tang Road, Hangzhou, 310014, People’s Republic of China, Tel +86-13705711671, Email zppurology@163.com; rori0610@graduate.hku.hkIntroduction: Bladder cancer (BCa) is among the most prevalent cancers worldwide. However, the effectiveness of intravesical therapy for BCa is limited due to the short dwell time and the presence of the permeation barrier.Methods: Nanocomplexes were self-assembled between DNA and hendeca-arginine peptide (R11). Stepwise intravesical instillation of R11 and the generated nanocomplexes significantly enhanced the targeting capacity and penetration efficiency in BCa therapy. The involved mechanism of cellular uptake and penetration of the nanocomplexes was determined. The therapeutic effect of the nanocomplexes was verified preclinically in murine orthotopic BCa models.Results: Nanocomplexes exhibited the best BCa targeting efficiency at a nitrogen-to-phosphate (NP) ratio of 5 but showed a lack of stability during cellular uptake. The method of stepwise intravesical instillation not only increased the stability and target specificity of the DNA component but also caused the delivered DNA to more effectively penetrate into the glycosaminoglycan layer and plasma membrane. The method promotes the accumulation of the delivered DNA in the clathrin-independent endocytosis pathway, directs the intracellular trafficking of the delivered DNA to nonlysosome-localized regions, and enables the intercellular transport of the delivered DNA via a direct transfer mechanism. In preclinical trials, our stepwise method was shown to remarkably enhance the targeting and penetration efficiency of DNA in murine orthotopic BCa models.Conclusion: With this method, a stepwise intravesical instillation of self-assembled nanocomplexes, which are generated from hendeca-arginine peptides, was achieved; thus, this method offers an effective strategy to deliver DNA to target and penetrate BCa cells during gene therapy and warrants further development for future intravesical gene therapy in the clinical context.Graphical Abstract: Keywords: bladder cancer, intravesical therapy, DNA delivery, direct transfer

Site-specific drug delivery systems can contribute to the development and execution of effective cancer treatment. Due to its favorable features (including high biocompatibility, high hydrophilicity and ease of functionalization), poly(ethylene glycol) (PEG) has been widely adopted to design drug carriers. Generating carriers for delivery of hydrophobic anticancer agents, however, is still a challenge in carrier design.In the first step, PEG is functionalized with dialdehyde to generate PEG-(CHO)The chemical functionalities of the drug conjugate are confirmed by FTIR, H-NMRand XRD analysis.The release pattern of PEGDA-MN-DOX is investigated at 25 and 37 °C at different pH values. The results indicate that the developed drug conjugate cannot only behave as a sustained-release carrier, but can also generate a significant level of reactive oxygen species (ROS), leading to a high level of toxicity against MCF-7 cells while still showing excellent biocompatibility in 3T3 cells.The reported conjugate shows anticancer potential, cancer-targeting ability, and ROS-generating capacity for effective drug encapsulation and sustained release in chemotherapy.

HAPLN1 maintains aggregation and the binding activity of extracellular matrix (ECM) molecules (such as hyaluronic acid and proteoglycan) to stabilize the macromolecular structure of the ECM. An increase in HAPLN1 expression is observed in a few types of musculoskeletal diseases including rheumatoid arthritis (RA); however, its functions are obscure. This study examined the role of HAPLN1 in determining the viability, proliferation, mobility, and pro-inflammatory phenotype of RA- fibroblast-like synoviocytes (RA-FLSs) by using small interfering RNA (siHAPLN1), over-expression vector (HAPLN1OE), and a recombinant HAPLN1 (rHAPLN1) protein. HAPLN1 was found to promote proliferation but inhibit RA-FLS migration. Metformin, an AMPK activator, was previously found by us to be able to inhibit FLS activation but promote HAPLN1 secretion. In this study, we confirmed the up-regulation of HAPLN1 in RA patients, and found the positive relationship between HAPLN1 expression and the AMPK level. Treatment with either si-HAPLN1 or HAPLN1OE down-regulated the expression of AMPK-ɑ gene, although up-regulation of the level of p-AMPK-ɑ was observed in RA-FLSs. si-HAPLN1 down-regulated the expression of proinflammatory factors like TNF-ɑ, MMPs, and IL-6, while HAPLN1OE up-regulated their levels. qPCR assay indicated that the levels of TGF-β, ACAN, fibronectin, collagen II, and Ki-67 were down-regulated upon si-HAPLN1 treatment, while HAPLN1OE treatment led to up-regulation of ACAN and Ki-67 and down-regulation of cyclin-D1. Proteomics of si-HAPLN1, rHAPLN1, and mRNA-Seq analysis of rHAPLN1 confirmed the functions of HAPLN1 in the activation of inflammation, proliferation, cell adhesion, and strengthening of ECM functions. Our results for the first time demonstrate the function of HAPLN1 in promoting the proliferation and pro-inflammatory phenotype of RA-FLSs, thereby contributing to RA pathogenesis. Future in-depth studies are required for better understanding the role of HAPLN1 in RA.

The last decide has witnessed a growing research interest in the role of dietary phytochemicals in influencing the gut microbiota. On the other hand, recent evidence reveals that dietary phytochemicals exhibit properties of preventing and tackling symptoms of Alzheimer's disease, which is a neurodegenerative disease that has also been linked with the status of the gut microbiota over the last decade. Till now, little serious discussions, however, have been made to link recent understanding of Alzheimer's disease, dietary phytochemicals and the gut microbiota together and to review the roles played by phytochemicals in gut dysbiosis induced pathologies of Alzheimer's disease. Deciphering these connections can provide insights into the development and future use of dietary phytochemicals as anti-Alzheimer drug candidates. This review aims at presenting latest evidence in the modulating role of phytochemicals in the gut microbiota and its relevance to Alzheimer's disease and summarizing the mechanisms behind the modulative activities. Limitations of current research in this field and potential directions will also be discussed for future research on dietary phytochemicals as anti-Alzheimer agents.

Nanogels have high tunability and stability while being able to sense and respond to external stimuli by showing changes in the gel volume, water content, colloidal stability, mechanical strength, and other physical/chemical properties. In this article, advances in the preparation of nanogels will be reviewed. The application potential of nanogels in drug delivery will also be highlighted. It is the objective of this article to present a snapshot of the recent knowledge of nanogel preparation and application for future research in drug delivery.

The new variant of concern of SARS-CoV-2, namely Omicron, has triggered global fear recently. To date, our knowledge of Omicron, particularly of how S glycoprotein mutations affect the infectivity of the virus and the severity of the infection, is far from complete. This hinders our ability to treat the disease and to predict the future state of SARS-CoV-2 threats to well-being and economic stability. Despite this, efforts have been made to unveil the routes of transmission and the efficiency of existing vaccines in tackling Omicron. This article reviews the latest understanding of Omicron and the current status of the use of vaccines and drugs for infection control. It is hoped that this article can offer insights into the development of more effective measures to tackle the pandemic.

The human world is currently influenced largely by the outbreak of pandemic COVID‐19. At this moment, most researchers focus on developing treatment strategies and measures to work against COVID‐19. Treatment strategies specific for COVID‐19 are lacking. This article provides an overview of the life cycle and routes of transmission of SARS‐CoV‐2. The therapeutic effects of two drugs [i. e., remdesivir (RDV) and favipiravir (FPV)] which can potentially tackle COVID‐19 are discussed based on current published data. This review can serve as a reference for future studies., COVID‐19 is a pandemic that requires global action. This review presents the latest status of research on the use of two drugs (favipiravir and remdesivir) in tackling COVID‐19, and offers an overview of the life cycle and routes of transmission of SARS‐CoV‐2. It is hoped that the opportunities and challenges brought about by the use of these two drugs can be illuminated for future research.

Cancer has long been a hot research topic, and recent years have witnessed the incidence of cancer trending toward younger individuals with great socioeconomic burden. Even with surgery, therapeutic agents serve as the mainstay to combat cancer in the clinic. Intensive research on nanomaterials can overcome the shortcomings of conventional drug delivery approaches, such as the lack of selectivity for targeted regions, poor stability against degradation, and uncontrolled drug release behavior. Over the years, different types of drug carriers have been developed for cancer therapy. One of these is liposome-in-gel (LP-Gel), which has combined the merits of both liposomes and hydrogels, and has emerged as a versatile carrier for cancer therapy. LP-Gel hybrids have addressed the lack of stability of conventional liposomes against pH and ionic strength while displaying higher efficiency of delivery hydrophilic drugs as compared to conventional gels. They can be classified into three types according to their assembled structure, are characterized by their nontoxicity, biodegradability, and flexibility for clinical use, and can be mainly categorized based on their controlled release, transmucosal delivery, and transdermal delivery properties for anticancer therapy. This review covers the recent progress on the applications of LP-Gel hybrids for anticancer therapy.

Background Technical information regarding health-related advances is sometimes esoteric for the general public. News media, therefore, plays a key role in public health promotion via health information conveyance. In this study, we use China as a sample country and analyze the claims and frames in news coverage of health-related advances, with special focus on news coverage of the development and performance of newly developed or tested drugs. Methods A keyword search was performed to retrieve news articles from four representative news agencies in China. In total, 3029 news reports were retrieved, of which 128 were selected for further analysis. Results Four aspects of news coverage of drug development were identified: (1) the characteristics of new drugs covered, (2) the sources of information, (3) the accuracy of health information in newspapers, and (4) textual features of news coverage. Conclusions Our findings reveal that guidelines should be established to facilitate more systematic news reporting on health-related advances. Additionally, literacy among the general public and professionalism in health information conveyance should be promoted to negate the “illusion of knowing” about health-related advances.

miRNA is a class of short noncoding RNA that regulates gene expression at the post-transcriptional level. Evidence of age-associated changes in miRNA expression has been collected in models ranging from nematodes to humans; however, there has been little discussion of how to turn our knowledge of miRNA biology into antiaging therapy. This opinion article provides a snapshot of our current understanding of the roles of miRNA in modulating the aging process. We discuss major chemical techniques for modifying the miRNA structure as well as developing delivery systems for intervention. Finally, technical needs to be met for bench-to-clinic translation of miRNA-based interventions are highlighted for future research.

Soybeans and their food products exist in the market in various forms, ranging from crude oils and bean meals to nutritious products (e.g. soy milk powers). With the availability of technologies for mass production of soy products and for enrichment of soy components (e.g. phospholipids, saponins, isoflavones, oligosaccharides and edible fiber), the nutritional values of soy products have been enhanced remarkably, offering the potential for functional food development. Among different bioactive components in soybeans, one important component is isoflavones, which have been widely exploited for health implications. While there are studies supporting the health benefits of isoflavones, concerns on adverse effects have been raised in the literature. The objective of this article is to review the recent understanding of the biological activities, adverse effects, and use of isoflavones in functional food development.

Food packaging can extend the shelf life of food products and enhance the safety and quality of the food. This study reports food-grade polyelectrolyte complex films generated via electrostatic interactions between two cellulose-based agents [viz., hypromellose-graft-chitosan, and carmellose sodium]. At optimal conditions, our films show good barrier properties, high transparency, and high efficiency in post-production agent loading. They also demonstrate intrinsic antibacterial effects against both Gram-negative and Gram-positive bacteria. By using frozen chicken breasts as a model, the films enable real-time monitoring of the status of the frozen food due to the property of clusterisation-triggered emission. Along with their negligible toxicity, our films warrant further development as multi-functional films for effective and self-indicating food packaging.

Tumor neoantigen has a high degree of immunogenicity. As one of the emerging methods of tumor immunotherapy, the vaccine developed against it has served to clinical trials of various solid tumors, especially in the treatment of melanoma. Currently, a variety of immunotherapy methods have been applied to the treatment of the tumor. However, other therapeutic methods have the disadvantages of low specificity and prominent side effects. Treatments require tumor antigen with higher immunogenicity as the target of immune attack. This review will recommend the identification of neoantigen, the influencing factors of neoantigen, and the application of personalized vaccines for neoantigen in metastatic tumors such as malignant melanoma.

The incidence of cancer is increasing year by year. Cancer has become one of the health threats of modern people. Simply relying on the surgery, chemotherapy or radiotherapy, not only the survival rate is not high, but also the quality of life of patients is not much better. Fortunately, the emergence and rapid development of cancer immunotherapy have brought more and more exciting results. However, when scientists think it is possible to overcome cancer, they find that not all cancer patients can benefit from immunotherapy, that is to say, the overall efficiency of immunotherapy is not high. Drug resistance and side effects of immunotherapy cannot be ignored. In order to overcome these difficulties, scientists continue to improve the strategy of immunotherapy and find that combination therapy can effectively reduce the incidence of drug resistance. They also found that by reprogramming tumor blood vessels, activating ferroptosis, utilizing thioredoxin, FATP2 and other substances, the therapeutic effect can be improved and side effects can be alleviated. This article reviews the principles of immunotherapy, new strategies to overcome drug resistance of cancer immunotherapy, and how to improve the efficacy of immunotherapy and reduce side effects.

Liposomes are small spherical vesicles composed mainly of phospholipids and cholesterol. Over the years, a number of liposomal formulations have shown clinical promise, but the use of liposomes in oral drug delivery is limited. This is partly due to the vulnerability of conventional liposomes to the detrimental effect of gastrointestinal destabilizing factors and also to the poor efficiency in intestinal absorption of liposomes. Some of these issues can be ameliorated using the layer-by-layer (LbL) assembly technology, which has been widely applied to modify the surface of various nanoparticulate systems. Discussions about LbL functionalization of liposomes as oral drug carriers, however, are scant in the literature. To fill this gap, this review presents an overview of the roles of LbL functionalization in the development of liposomes, followed by a discussion about major principles of molecular design and engineering of LbL-functionalized liposomes for oral drug delivery. Regarding the versatility offered by LbL assembly, it is anticipated that LbL-functionalized liposomes may emerge as one of the important carriers for oral drug administration in the future.

Camptothecin (CMPT) in a free form is extremely cytotoxic as well as hydrophobic drug, and is considered to be highly contagious for systemic administration. The fibronectin (FN)-functionalized DNA-based nanocarrier has been designed to load CMPT and target integrin (αvβ3) receptors which are highly expressed on the A549 cancer cells. Here, we report DNA nanocarrier in the form of DNA-nanofibers (DNA-NFs) capable of loading CMPT via strand intercalation in the GC (base pairs)-rich regions of the DNA duplex. Hence, our keen purpose was to explore the potential of DNA-NFs to load CMPT and assess the improvements of the outcomes in terms of enhanced therapeutic effects to integrin-rich A549 cancer cells with reduced cytotoxic effects to integrin-lacking HEK293 cells. DNA-NFs were formulated as a polymer of DNA triangles. DNA triangles arranged in a programmed way through the complementary overhangs present at the vertices. DNA triangles were primarily obtained through the annealing of the freshly circularized scaffold strands with the three distinct staple strands of specific sequences. The polymerized triangular tiles instead of forming two-dimensional nanosheets underwent self-coiling to give rise to DNA-NF-shaped structures. Flow cytometry and MTT assays were performed to observe cytotoxic and apoptotic effects on integrin-rich A549 cancer cells compared with the integrin-deficient HEK293 cells. AFM, native-page, and confocal experiments confirmed the polymerization of DNA triangles and the morphology of the resulting nanostructures. AFM and confocal images revealed the length of DNA-NFs to be 3-6 μm and the width from 70 to 110 nm. CMPT loading (via strands intercalation) in GC-rich regions of DNA-NFs and the FN functionalization (TAMRA tagged; red fluorescence) via amide chemistry using amino-modified strands of DNA-NFs were confirmed through the UV-shift analysis ( 10 nm shift) and confocal imaging. Blank DNA-NFs were found to be highly biocompatible in 2-640 μM concentrations. MTT assay and flow cytometry experiments revealed that CMPT-loaded DNA-NFs showed a dose-dependent decrease in the cell viability to integrin-rich A549 cancer cells compared with the integrin-deficient HEK293 cells. Conclusively, FN-functionalized, CMPT-loaded DNA-NFs effectively destroyed integrin-rich A549 cancer cells in a targeted manner compared with integrin-deficient HEK293 cells. Grapical abstract.

Development of methods for manipulating and culturing stem cells has enabled the emergence of stem cell therapy as a promising approach in diverse applications, ranging from tissue repair to treatment of intractable diseases such as diabetes, cardiovascular diseases and neurological disorders. Along with technological advances in systemic stem cell delivery, treating multiple injured or pathological sites simultaneously has been made possible. Despite this, most of the works on systemic stem cell transplantation at the moment have focused on the efficiency of tackling local disorders. The prospect of the therapy for enhancing systemic tissue repair, as well as for tackling systemic degenerative disorders, has rarely been seriously considered. The objective of this article is to fill this gap by reviewing the current status of research on systemic stem cell delivery, and by presenting the opportunities and challenges for translating systemic stem cell delivery from the laboratory to the clinic.

Hutchinson–Gilford progeria syndrome (HGPS) is an autosomal‐dominant genetic disease that leads to accelerated aging and often premature death caused by cardiovascular complications. Till now clinical management of HGPS has largely relied on the treatment of manifestations and on the prevention of secondary complications, cure for the disease has not yet been established. Addressing this need cannot only benefit progeria patients but may also provide insights into intervention design for combating physiological aging. By using the systematic review approach, this article revisits the overall progress in the development of strategies for HGPS treatment over the last ten years, from 2010 to 2019. In total, 1,906 articles have been retrieved, of which 56 studies have been included for further analysis. Based on the articles analyzed, the trends in the use of different HGPS models, along with the prevalence, efficiency, and limitations of different reported treatment strategies, have been examined. Emerging strategies for preclinical studies, and possible targets for intervention development, have also been presented as avenues for future research., Hutchinson–Gilford progeria syndrome is an autosomal‐dominant genetic disease which has no cure right now. Development of therapies has clinical importance and may provide a window into the mechanism and treatment of physiological aging.

Hydrogels are swellable polymer networks which can imbibe a substantial amount of fluids. Compared to bulk hydrogels, hydrogel nanoparticles exhibit added values in drug delivery because they can be internalized into cells to deliver pharmaceutical agents into the cytosol. Their large surface area also allows for multivalent conjugations, making optimization of the nanoparticles towards in vivo and clinical applications possible. These features, together with the tunable properties and biocompatibility of hydrogels, account for the widespread use of hydrogel-based nanoparticulate systems in drug formulation. From an in vivo perspective, this article presents the latest advances in fabrication and engineering of hydrogel nanoparticles, and illuminates future avenues to enhance the potential of hydrogel-based nanoparticulate systems in treatment development and drug administration.

The integrity of the cytoskeleton is essential to diverse cellular processes such as phagocytosis and intracellular trafficking. Disruption of the organization and dynamics of the actin cytoskeleton leads to age-associated symptoms and diseases, ranging from cancer to neurodegeneration. In addition, changes in the integrity of the actin cytoskeleton disrupt the functioning of not only somatic and stem cells but also gametes, resulting in aberrant embryonic development. Strategies to preserve the integrity and dynamics of the cytoskeleton are, therefore, potentially therapeutic to age-related disorders. The objective of this article is to revisit the current understanding of the roles played by the actin cytoskeleton in aging, and to review the opportunities and challenges for the transition of basic research into intervention development. It is hoped that, with the snapshot of evidence regarding changes in actin dynamics with advanced age, insights into future research directions can be attained.

Doxorubicin (Dox) being a hydrophobic drug needs a unique carrier for the effective encapsulation with uniformity in the aqueous dispersion, cell culture media and the biological-fluids that may efficiently target its release at the tumor site. Circular DNA-nanotechnology was employed to synthesize DNA Nano-threads (DNA-NTs) by polymerization of triangular DNA-tiles. It involved circularizing a linear single-stranded scaffold strand to make sturdier and rigid triangles. DNA-NTs were characterized by the AFM and Native-PAGE tests. Dox binding and loading to the Neuregulin1 (NRG1) functionalized DNA based nano-threads (NF-DBNs) was estimated by the UV-shift analysis. The biocompatibility of the blank NRG-1/DNA-NTs and enhanced cytotoxicity of the NF-DBNs was assessed by the MTT assay. Cell proliferation/apoptosis was analyzed through the Flow-cytometry experiment. Cell-surface binding and the cell-internalization of the NF-DBNs was captured by the double-photon confocal microscopy (DPCM). The AFM images revealed uniform DNA-NTs with the diameter 30 to 80 nm and length 400 to 800 nm. PAGE native gel was used for the further confirmation of the successful assembly of the strands to synthesize DNA-NTs that gave one sharp band with the decreased electrophoretic mobility down the gel. MTT assay showed that blank DNA-NTs were biocompatible to the cells with less cytotoxicity even at elevated concentrations with most of the cells (94%) remaining alive compared to the dose-dependent enhanced cytotoxicity of NF-DBNs further evidenced by the Flow-cytometry analysis. Uniform and stiffer DNA-NTs for the potential applications in targeted drug delivery was achieved through circular DNA scaffolding.

DNA based nano-carriers synthesized from short circular scaffolds (circular DNA nanotechnology) attains stiffer topology for ligand functionalization (neuregulin-1/NRG-1 ligand) and biological applications (targeted drug delivery). Daunorubicin (DR) is a hydrophobic chemical that requires robust vectors to efficiently encapsulate and avoid its free dispersion in water, biological media and cell culture. Here we design DNA nanospindels (DNA-NS) to efficiently load DR and target the (highly expressed) HER2/neu receptors on the plasma membrane of drug-resistant MCF-7 (breast cancer) cells. DNA-NS were synthesized by polymerizing the DNA-triangles (utilizing 84-nt short circular scaffold strand) into larger DNA nano-ribbons characterized by the native-PAGE testing. AFM results revealed the spinning of DNA nanoribbons on its (own) axis because of the intrinsic curvature of the DNA double helix resulting in the formation of the firm and twisted DNA-NS with the diameter (50–70 nm) and length (0.5–4 μm). DA loading onto DNA-NS was confirmed by the UV shift analysis. The MTT results with the blank DNA-NS evidenced its biocompatibility (remained value of 93%) compared to the decreased viability of the MCF-7 cells after treatment with DNA-NS (DR loaded). These findings were further supported by the analysis of cell proliferation/apoptosis through flow cytometry showing 64% apoptosis after treating with the DR loaded DNA-NS. Hence, through the short circular DNA nanotechnology, we have achieved a stiffer, uniform, and biocompatible DNA-NS for applications in the targeted therapy.

Polymeric carriers have emerged as major non-viral alternatives for gene delivery due to their lower immunogenicity and pathogenicity. However, during intracellular delivery of these carriers, multiple barriers have to be overcome or the efficiency of gene delivery will be impeded. A thorough understanding of these cellular impediments is pivotal to optimizing the efficiency of polymer-based gene delivery. This review delineates the major barriers encountered during intracellular delivery of polyplexes and discusses possible molecular designs to overcome these barriers. Based on a review of the latest strategies to enhance the intracellular delivery process, we provide insights into the further development of polymeric carriers with enhanced efficiency in transfection.

New products that help make human tissue and organ regeneration more effective are in high demand and include materials, structures and substrates that drive cell-to-tissue transformations, orchestrate anatomical assembly and tissue integration with biology. Marine organisms are exemplary bioresources that have extensive possibilities in supporting and facilitating development of human tissue substitutes. Such organisms represent a deep and diverse reserve of materials, substrates and structures that can facilitate tissue reconstruction within lab-based cultures. The reason is that they possess sophisticated structures, architectures and biomaterial designs that are still difficult to replicate using synthetic processes, so far. These products offer tantalizing pre-made options that are versatile, adaptable and have many functions for current tissue engineers seeking fresh solutions to the deficiencies in existing dental biomaterials, which lack the intrinsic elements of biofunctioning, structural and mechanical design to regenerate anatomically correct dental tissues both in the culture dish and in vivo.

MicroRNAs (miRNAs) have emerged as key post-transcriptional regulators of gene expression, and have displayed important roles in areas spanning from embryonic development to skin physiology. Despite this, till now little is known about the significance of miRNAs in cutaneous wound healing. In this mini-review, we discuss the existing evidence on the roles of miRNAs in physiological processes relevant to cutaneous wound healing, followed by a highlight of the prospects and challenges of future development of miRNA-based wound therapies. With existing technologies of nucleic acid transfer and miRNA modulation, it is anticipated that once the roles of miRNAs in wound healing have been clarified, there will be a vast new vista of opportunities brought up for development of miRNA-targeted therapies for wound care.

Prolongation of longevity is a history-long desire of humans. Driven by the genetic contribution to longevity and the remarkable plasticity of healthy lifespan as demonstrated in animal models, arduous efforts have been directed to aging and longevity research over the years. Today, our understanding of lifespan determination is much greater than it was in the past, but administrable interventions for longevity enhancement are still virtually absent. The aim of this article is to highlight the technical gap between basic biogerontological research and intervention development, and to explore the importance of nucleic acid (NA) delivery technologies in bridging the gap. It is hoped that this article can engender more awareness of the roles of NA delivery technologies in biogerontological interventions, particularly NA therapy.

Multidrug therapy may yield higher therapeutic effects as compared to monotherapy, yet its wide application has been hampered by the limitations of conventional drug delivery systems, in which not only incompatible drugs cannot be co-delivered but also the release rates of individual co-delivered drugs cannot be tuned separately. Regarding these limitations, we adopt the microfluidic electrospray technology to fabricate alginate-based multicompartment microgel beads. By using cadmium-telluride (CdTe) quantum dots (QDs) and a quenching agent as a model pair, the beads are shown to effectively separate incompatible drugs during co-delivery, and significantly prolong the time of observable fluorescence emission from QDs co-delivered with a quenching agent. Moreover, the drug release rates from different compartments can be tuned using the polymer blending technique to achieve a variety of drug release patterns. This study is one of the first to adopt the microfluidic electrospray technology to generate microgel beads with such versatility for co-delivery of multiple drugs. Our results provide evidence for the promising potential of our beads to be further developed as a carrier for multidrug therapy and other applications that require co-administration of multiple bioactive agents.

Proteins have emerged as an important class of therapeutic agents due to their high specificity in their physiological actions. Over the years, diverse protein carriers have been developed; however, some concerns, such as the relatively low loading efficiency and release sustainability, have limited the efficiency of protein delivery. This study reports the use of hydrogel nanoparticles based on a novel copolymer, poly(ethylenimine)-graft-polysorbate (PEIP), as effective protein carriers. The copolymer is fabricated by grafting poly(ethylenimine) (PEI) with polysorbate 20 using carbonyldiimidazole chemistry. Its cytotoxicity is much lower than that of unmodified PEI in RGC5 and HEK293 cells. In comparison with nanoparticles formed by unmodified PEI, our nanoparticles are not only more efficient in cellular internalization, as indicated by the 5- to 6-fold reduction in the time they take to cause 90% of cells to exhibit intracellular fluorescence, but also give a protein loading efficiency as high as 70-90%. These, together with the salt-responsiveness of the nanoparticles in protein release and the retention of the activity of the loaded protein, suggest that PEIP and its hydrogel nanoparticles warrant further development as protein carriers for therapeutic applications.

Coriolus versicolor is an herb widely used for cancer treatment in traditional Chinese medicine. Its active ingredients, polysaccharopeptides (PSP), have been used for adjuvant therapies in cancer treatment. This study conjugates Coriolus versicolor PSP with poly(ethylenimine) (PEI) to generate a PSP-PEI copolymer for gene transfer. After PEI conjugation, both the pH buffering capacity and DNA compaction ability of PSP are significantly increased. Compared with that of PSP, the transfection efficiency of PSP-PEI is 10 to 20-fold higher in vitro. This is a proof-of-concept study reporting the direct use of bioactive phytochemicals from traditional Chinese medicine for gene vector development. The promising performance of PSP-PEI raises the possibility that bioactive herbal ingredients can be further developed as a multi-therapeutic gene carrier for tackling cancers.

Summary Nursing shortages are an international issue and are particularly evident in perioperative care, critical care and emergency services. The solution commonly adopted to tackle this problem is to increase the recruitment of nurses to replace the loss, whereas efforts to try and retain existing staff have only sporadically been mentioned. Furthermore, while retention programmes have occasionally received attention from some nursing scholars, they often fail to investigate the real needs of nurses. This article discusses three practical solutions adopted in Hong Kong, which could potentially alleviate difficulties with staff retention. It is hoped that the collaborative efforts of different professionals and nursing scholars will help to solve nursing shortages in the foreseeable future.

Microfluidics is a compelling technology that shows considerable promise in applications ranging from gene expression profiling to cell-based assays. Owing to its capacity to enable generation of single droplets and multiple droplet arrays with precisely controlled composition and a narrow size distribution, recently microfluidics has been exploited for delivery of genes. This article provides an overview of recent advances in microfluidic gene delivery, and speculates the prospects for further research. The objectives of this article are to illustrate the potential roles played by microfluidics in gene delivery research, and to shed new light on strategies to enhance the efficiency of gene therapy.

Successful gene therapy necessitates safe and efficient gene transfer. This article describes the use of a cationic polymer, which was synthesized by cross-linking low molecular weight branched poly(ethylenimine) (PEI) with both β-cyclodextrin and propane-1,2,3-triol, for efficient and safe non-viral gene delivery. Experimentation demonstrated that the polymer had a pH buffering capacity and DNA condensing ability comparable to those of PEI 25 kDa. In B16-F0 cells, the polymer increased the transfection efficiency of naked DNA by 700-fold and yielded better transfection efficiencies than Fugene HD (threefold higher) and PEI 25 kDa (fivefold higher). The high transfection efficiency of the polymer was not affected by the presence of serum during transfection. In addition to B16-F0 cells, the polymer enabled efficient transfection of HepG2 and U87 cells with low cytotoxicity. Our results indicated that our polymer is a safe and efficient transfection reagent that warrants further development for in vitro, in vivo and clinical applications.

Use of ceramics and polymers continues to dominate clinical procedures in modern dentistry. Polymers have provided the basis for adhesives, tissue void fillers, and artificial replacements for whole teeth. They have been remarkably effective in the clinic at restoration of major dental functions after damage or loss of teeth. With the rapid development of polymer science, dental materials science has significantly lagged behind in harnessing these advanced polymer products. What they offer is new and unique properties superior to traditional polymers and crucially a range of properties that more closely match natural biomaterials. Therefore, we should pursue more vigorously the benefits of advanced polymers in dentistry. In this review, we highlight how the latest generation of advanced polymers will enhance the application of materials in the dental clinic using numerous promising examples. Polymers have a broad range of applications in modern dentistry. Some major applications are to construct frameworks that mimic the precise structure of tissues, to restore tooth organ function, and to deliver bioactive agents to influence cell behavior from the inside. The future of polymers in dentistry must include all these new enhancements to increase biological and clinical effectiveness beyond what can be achieved with traditional biomaterials.

Continuous replacement of teeth throughout the lifespan of an individual is possibly basal for most of the vertebrates including fish and reptiles; however, mammals generally have a limited capacity of tooth renewal. The ability to induce cellular differentiation in adults to replace lost or damaged cells in mammals, or to tissue-engineer organs in vitro, has hence become one of the major goals of regenerative medicine. In this article, we will revisit some of the important signals and tissue interactions that regulate mammalian tooth development, and will offer a synopsis of the latest progress in tooth regeneration and repair via molecular and engineering approaches. It is hoped that this article will not only offer an overview of recent technologies in tooth regeneration and repair but will also stimulate more interdisciplinary research in this field to turn the pursuit of tooth regeneration and repair into practical reality.

Protein kinases are enzymes that catalyze the transfer of γ phosphate from adenosine triphosphate to substrate proteins, and are important signal transduction mediators in a diversity of biological processes, ranging from apoptosis to energy metabolism. In this article, we will take this prominent class of proteins as an example to illustrate the involvement of proteins in modulation of aging and to highlight the prospects and challenges of protein-targeted interventions for anti-aging purposes. It is hoped that through this article, more empirical work on interventive gerontology will follow, and with collaborative endeavors among researchers, hurdles in anti-aging intervention development can be overcome in the near future.

This study sought to investigate, with a focus on the Hong Kong context, how commercial slimming websites portray the body image of beauty to the public, and to explore practical implications for related public health practices and health policy formulation. Commercial entities in the Hong Kong slimming industry were retrieved from the Hong Kong Yellow Page Directory and Yahoo Hong Kong Directory, and selected websites were coded and further analyzed. We found that irresponsible tactics are used in the slimming industry such that irresponsible messages prevail. Collaborative efforts from multidisciplinary sectors are needed to tackle the situation.

Pursuance of longevity is not only combating decrepitude but it is also extending the health span; otherwise longevity would result in a universal medical and social burden. As revealed by the literature, the attainment of a healthy life could be impacted by the social milieu. An inquiry of this kind could hardly be settled by mere laboratory endeavors, and thus serious discussion of the social dimension of life span extension is imperative. However, little attention has been paid to this need in the biogerontological field. In view of this gap, the aim of this article is to explore the health relationship of the social milieu by using social relations as an example and to raise the awareness within our biogerontological community of the relevance of the social milieu to our existing efforts on longevity pursuance. It is hoped that through this article and with the success of antiaging therapies, not only could collaborative work between biogerontologists and scholars in other disciplines be stimulated, but indefinite extension of both life span and health span could also be achieved in the future.

Combined chemo-gene therapy is one of the treatment modalities that have attracted extensive research interests; however, there is little information regarding the influence of drug application on gene transfer. This study bridges this gap by examining how chemotherapeutic drugs (teniposide, cis-diamminedichloroplatinum(II) and temozolomide) interfere with polyplex formation and transfection of chitosan-graft-poly(ethylenimine). Our results indicate that the degree of drug interference varies with the mechanism of drug action, with the transgene expression being severely suppressed when the plasmid is co-delivered with cis-diamminedichloroplatinum(II) or teniposide but not temozolomide. In addition, the interference with transfection by drugs varies with different gene/drug co-formulations. This is the first study to evidence that, though combined chemo-gene therapy has therapeutic potential, some chemotherapeutic drugs may reduce the treatment efficiency of gene therapy.