Observing the effect of physical activity on forward head posture and rounded shoulder posture in young healthy adults.

[Purpose] This study aimed to examine the effects of physical activity on forward head and rounded shoulder postures in healthy young adults. [Participants and Methods] We recruited 20 healthy young adults engaged in high levels of physical activity and 20 healthy young adults engaged in low levels of physical activity. Both groups completed the International Physical Activity Questionnaire (IPAQ) to assess their physical activity levels. The scapular index (SI) was calculated to assess rounded shoulder posture, whereas the craniovertebral angle (CVA) was calculated to assess forward head posture. Differences in SI and CVA between the two groups were examined. [Results] There was a significant difference in the SI between the two groups, with the low physical activity group exhibiting a lower SI than the high physical activity group. However, there was no significant difference in the CVA between the two groups. [Conclusion] Our study showed that low physical activity levels in healthy young adults could negatively affect shoulder posture but not head posture. Therefore, regularly monitoring rounded shoulder posture in individuals with low physical activity levels is recommended for health considerations.

The clinical significance and mechanism of microRNA-22-3p targeting TP53 in lung adenocarcinoma.

BACKGROUND: At present, studies on MircoRNA-22-3p (miR-22-3p) in lung adenocarcinoma use a single method, lack multi-center validation and multi-method validation, and there is no big data concept to predict and validate target genes. OBJECTIVE: To investigate the expression, potential targets and clinicopathological significance of miR-22-3p in lung adenocarcinoma (LUAD) tissues. METHODS: LUAD formalin-fixed paraffin-embedded (FFPE) tumors and adjacent normal lung tissues were collected for real-time quantitative polymerase chain reaction (RT-qPCR). Collect miR-22-3p in LUAD and non-cancer lung tissue from high-throughput datasets, standardized mean difference (SMD) and area under the curve (AUC) of the comprehensive receiver operating curve (summary receiver operating characteristic cure, sROC curve) were calculated. Cell function experiments on A549 cells transfected with LV-hsa-miR-22-3p. Target genes were predicted by the miRwalk2.0 website and the resulting target genes were subjected to Gene Ontology (GO) pathway enrichment analysis and constructed to protein-protein interaction network. Finally, the protein expression level of the key gene TP53 was validated by searching The Human Protein Atlas (THPA) database to incorporate TP53 immunohistochemical results in LUAD. RESULTS: RT-qPCR result from 41 pairs of LUAD and adjacent lung tissues showed that miR-22-3p was downregulated in LUAD (AUC = 0.6597, p= 0.0128). Globally, a total of 838 LUADs and 494 non-cancerous lung tissues were included, and were finally combined into 14 platforms. Compared with noncancerous tissue, miR-22-3p expression level was significantly reduced in LUAD tissue (SMD =-0.32, AUC = 0.72l); cell function experiments showed that miR-22-3p has inhibitory effects on cell proliferation, migration and invasion, and has promotion effect on apoptosis. Moreover, target genes prediction, GO pathway enrichment analysis and PPI network exhibited TP53 as a key gene of target gene of miR-22-3p; at last, a total of 114 high-throughput datasets were included, including 3897 LUADs and 2993 non-cancerous lung tissues, and were finally combined into 37 platforms. Compared with noncancerous tissue, TP53 expression level was significantly increased in LUAD (SMD = 0.39, p< 0.01) and it was verified by the protein expression data from THPA. CONCLUSION: Overexpression of miR-22-3p may inhibit LUAD cell proliferation, migration and invasion through TP53, and promote cell apoptosis.

Establishment and validation of a prognostic immune-related lncRNA risk model for acute myeloid leukemia.

Background: Acute myeloid leukemia (AML) is a cancer arising in the bone marrow and is the most common type of adult leukemia. AML has a poor prognosis, and currently, its prognosis evaluation does not include immune status assessment. This study established an immune-related long non-coding RNA (lncRNA) prognostic risk model for AML based on immune lncRNAs screening. Methods: To construct training and validation cohorts, The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) public databases were accessed to obtain gene expression profiles and clinical data. The correlation between lncRNAs and immunity genes was analyzed using the "limma" package, and the immune-related lncRNAs were obtained. Through least absolute shrinkage and selection operator regression, a prognostic model was established with immune-related lncRNAs. Using the median risk score, patients were divided into high- and low-risk groups. The Kaplan-Meier method was used for survival analysis, whereas the accuracy of the risk model was evaluated using time-dependent receiver operating characteristic curves, risk score distribution, survival status, and risk heat maps. We utilized univariate and multivariate Cox regression to examine the association between risk score and clinical variables and AML survival and prognosis. Results: In the immune-related lncRNA prognostic risk model, the prognosis was better for low-risk than for high-risk patients, indicating risk score of this model as an independent indicator of prognosis. The area under the curve value for 1-, 3-, and 5-year survival of TCGA patients was 0.817, 0.859, and 0.909, respectively, whereas that of GEO patients (of dataset GPL96-GSE37642) was 0.603, 0.652, and 0.624, respectively. Gene set enrichment analysis revealed the enrichment of multiple pathways, such as antigen processing, B-cell receptor signaling pathway, natural killer cell-mediated cytotoxicity, and chemokines, in high-risk patients. Conclusions: In this study, immune-related lncRNA prognostic risk models effectively predicted AML survival and provided potential treatment targets.

A Dual-Mode Multifunctional Pulsed Radio-Frequency Stimulator for Trigeminal Neuralgia Relief and its Animal Model.

This work proposed a programmable pulsed radio-frequency (PRF) stimulator for trigeminal neuralgia (TN) relief on demand. The implantable stimulator is a miniaturized micro-system which integrates a wireless interface circuit, a sensor interface circuit, a PRF pattern generation circuit and a logic controller. The multifunctional stimulator capable of delivering current/voltage stimulation provides the choice of the biphasic sinusoidal, square and patterned waveform for PRF treatment researches. The external handheld device can wirelessly transmit the parameters of frequency, amplitude, pulse duration and repetition rate of the pulse train to the implanted stimulator. While stimulating, the temperature sensor can monitor the operating temperature. The feedback signal is transmitted in medical implanted communication system (MICS). The micro-system is fabricated in a 0.35 µm CMOS process with a chip size of 3.1 × 2.7 mm2. The fabricated chip was mounted on a 2.6 × 2.1 cm2 test board for studying the in vivo efficacy of pain relief by PRF. Animal studies of PRF stimulation and commonly-used medication for trigeminal neuralgia are also demonstrated and the presented results prove that PRF stimulation has greater effectiveness on trigeminal neuralgia relief comparing to the medication. The effectiveness period lasts at least 14 days. The results of neural recording show that the PRF stimulation of trigeminal ganglion (TG) attenuated neuron activities without being severely damaged. Pathology also revealed no lesion found on the stimulated area.

Enhanced anticancer effect of ROS-boosted photothermal therapy by using fucoidan-coated polypyrrole nanoparticles.

Nanomaterial mediated cancer/tumor photo driven hyperthermia has obtained great awareness. Nevertheless, it is a challenge for improving the hyperthermic efficacy lacking resistance to stimulated thermal stress. We thus developed a bioinspired nano-platform utilizing inclusion complexation between photosensitive polypyrrole (Ppy) nanoparticles (NP) and fucoidan (FU). This FU-Ppy NP proved to be an excellent P-selectin-mediated, lung cancer-cell/tumor targeting delivery and specific accumulation, could augment cancer/tumor oxidative stress levels through producing cellular reactive oxygen species. Potent ROS/photothermal combinational therapeutic effects were exhibited by the bioinspired FU-Ppy NP through a selective P-selectin cancer/tumor targeting aptitude for the lung cancer cells/tumor compared with other nano-formulations. The usage of FU-Ppy NP also involves the potential mechanism of suppressing the biological expression of tumor vascular endothelial growth factor (VEGF). This FU biological macromolecule-amplified photothermally therapeutic nano-platform has promising potential for future medical translation in eradicating numerous tumors.

A smart and active film with tunable drug release and color change abilities for detection and inhibition of bacterial growth.

Antimicrobial resistance has become a global issue and thus the development of natural products/biomedical materials composites with antibacterial activities is urgently needed. When acute wounds develop into chronic wounds, the wound environments become alkaline. As long as infections occur, the wound pH further increases, making the wounds difficult to heal. Besides, bacterial growth in poultry, meat, fish and seafood products is usually reflected in a marked increase of pH values. Herein, smart, stimuli responsive self-assembled multilayer and complex film were constructed through the formation of hydrogen bonds and hydrophobic interactions between hydroxypropyl methylcellulose (HPMC) and epigallocatechin-3-gallate (EGCG), thereby greatly reducing the hydrophilicity of HPMC and offering enhanced mechanical strength, superior free radical scavenging capability, and improved water vapor and light barrier properties. The EGCG/HPMC complex film was able to control EGCG release by tuning pH or temperature of the release medium. Furthermore, incorporation of CuS nanoparticles into the film allowed it to triggers EGCG release in an on-demand fashion under near-infrared (NIR) exposure. Bacterial growth in glucose-free nutrient broth medium caused pH to rise (near pH 8.0), leading to transformation of EGCG from phenol type to phenolate ion and then quinone, allowing for spontaneous generation of H2O2 to kill bacteria. The complex films changed their color in response to bacterial growth because EGCG transformed from phenol type to quinone type under alkaline condition. The green synthesized EGCG/HPMC complex films can be used as a colorimetric pH indicator and an antibacterial material for wound dressing and food packaging applications.

Synthesis and characterization of Gd-DTPA/fucoidan/peptide complex nanoparticle and in vitro magnetic resonance imaging of inflamed endothelial cells.

P-selectin overexpressed on activated endothelial cells and platelets is a new target for treatment of cancers and cardiovascular diseases such as atherosclerosis and thrombosis. In this study, depolymerized low molecular weight fucoidan (LMWF8775) and a thermolysin-hydrolyzed protamine peptide (TPP1880) were prepared. TPP1880 and LMWF8775 were able to form self-assembled complex nanoparticles (CNPs). The formation of TPP1880/LMWF8775 CNPs was characterized by Fourier-transform infrared spectra, circular dichroism spectra and isothermal titration calorimetry. The CNPs selectively targeted PMA-stimulated, inflamed endothelial cells (HUVECs) with high expression of P-selectin. Gd-DTPA MRI contrast agent was successfully loaded in the CNPs with better T1 relaxivity and selectively accumulated in the activated HUVECs with increased MRI intensity and reduced cytotoxicity as compared to free Gd-DTPA. Our results suggest that the TPP1880/LMWF8775 CNPs may have potential in future for early diagnosis of cardiovascular diseases and cancers in which the endothelium is inflamed or activated.

Fucoidan-based, tumor-activated nanoplatform for overcoming hypoxia and enhancing photodynamic therapy and antitumor immunity.

Multifunctional nanoplatforms combined with photodynamic therapy (PDT) and anticancer drugs have shown great promising in cancer therapy. However, their efficacy is limited by the low specificity, low oxygen levels, and a tolerant tumor immune microenvironment. Herein, we developed a biocompatible theranostic nanoplatform (FM@VP) based on co-assembly of a nanocomplex formed by a functional polysaccharide fucoidan and a bioreducible polyamidoamine (PAMAM) dendrimer, a photosensitizer verteporfin (VP), and MnO2 nanoparticles (a tumor microenvironment responsive oxygen evolving nanomaterial) into a multifunctional nanoparticle cluster. The dendrimer-fucoidan polyionic nanocomplex (DFPN) specifically targeted P-selectin-overexpressed triple-negative breast cancer (TNBC) and the tumor-associated vasculature, and was sensitive to glutathione (GSH) in tumor. More importantly, this FM@VP nanocomplex simultaneously overcame tumor hypoxia, suppressed oncogenic signaling, and attenuated tumor-mediated immunosuppression, resulting in improving therapeutic efficacy of PDT while enhancing antitumor immunity and anti-metastasis. This discovery provides a powerful strategy for synergetic cancer targeting/photodynamic/immunotherapy and could serve as a safe clinical translational approach.

Characterization and toxicology evaluation of low molecular weight chitosan on zebrafish.

Chitosan is suggested as no or low toxicity and biocompatible biomaterial. Digestion of chitosan to reduce molecular weight and formulate nanoparticle was generally used to improve efficiency for DNA or protein delivery. However, the toxicity of low-molecular-weight chitosan (LMWCS) towards freshwater fishes has not been well evaluated. Here, we reported the toxic mechanism of LMWCS using zebrafish (Danio rerio) liver (ZFL) cell line, zebrafish larvae, and adult fish. LMWCS rapidly induced cytotoxicity of ZFL cells and death of zebrafish. Cell membrane damaged by LMWCS reduced cell viability. Damaged membrane of epithelial cell in zebrafish larvae induced breakage of the yolk. Adult fish exhibited hypoxia before death due to multiple damages induced by LMWCS. Although the toxicity of LMWCS was revealed in zebrafish model, the toxicity was only present in pH < 7 and easy be neutralized by other negative ions. Collectively, these data improved a new understanding of LMWCS properties.

Development of bacterial cellulose/chitin multi-nanofibers based smart films containing natural active microspheres and nanoparticles formed in situ.

Nanofiber-based materials have recently gained increasing attention in food packaging, drug delivery, and biomedical applications. In this study, a multi-nanofibers composite film was developed based on bacterial cellulose nanofiber (BCNF)/chitin nanofiber (CNF) hybridization. The nanofibers were responsible for the formation of well-dispersed curcumin (Cur) micro/nanoparticles in the nanocomposite films. The release of Cur from the films were affected by CNF and the sizes of Cur particles formed in situ. The Cur particles reduced tensile strength and increased water vapor permeability of BCNF film. However, CNF improved the mechanical strength and barrier property of the Cur/BCNF/CNF composite film. Moreover, the multi-nanofibers composite film showed excellent dynamic antioxidant capacity and antibacterial activity, as well as was capable to monitor pH change and trace amount of boric acid. Results of this study suggested that the Cur/BCNF/CNF composite film can be used as a smart and active food packaging material.

Association between ambient air pollution and out-of-hospital cardiac arrest: are there potentially susceptible groups?

This study aimed to examine the association between air pollution and out-of-hospital cardiac arrest (OHCA), and the effects of underlying diseases. Between January 2015 and December 2016, data on particulate matter (PM)2.5 and other air pollutants in Kaohsiung City were collected, and an emergency medical service database was used for information on patients who experienced OHCA. Overall, 3566 patients were analyzed and subgroup analyses by sex, age, and preexisting morbidities were performed. Interquartile increments in PM2.5, PM10, and O3 levels on lag 1 and NO2 level on lag 3 were associated with increments of 10.8%, 11.3%, 6.2%, and 1.7% in OHCA incidence, respectively. Subgroup analyses showed that patients with diabetes (1.363; interaction p = 0.009), heart disease (1.612; interaction p = 0.001), and advanced age (≥70 years, 1.297; interaction p = 0.003) were more susceptible to NO2 on lag 3. Moreover, patients were more susceptible to O3 during the cold season (1.194; interaction p = 0.001). We found that PM2.5, PM10, NO2, and O3 may play an important role in OHCA events, and the effects vary by underlying condition, age and season.

Serratus Anterior and Upper Trapezius Electromyographic Analysis of the Push-Up Plus Exercise: A Systematic Review and Meta-Analysis.

CONTEXT: Whereas the serratus anterior (SA) and the upper trapezius (UT) work as a force couple for scapular motion, weakness of the SA and overactivation of the UT are often present in overhead athletes with shoulder dysfunction. Therefore, researchers addressing an intramuscular imbalance between the SA and UT have focused on finding exercises that target the weak SA and minimally activate the UT. OBJECTIVE: To compare the effectiveness of push-up plus (PUP) exercise variants based on the electromyographic (EMG) activity of the SA and UT. DATA SOURCES: A systematic search of PubMed and Scopus between January 1, 2000, and March 31, 2008. STUDY SELECTION: Studies of PUP exercises that involved EMG analysis. DATA EXTRACTION: We assessed study quality using the Critical Appraisal Skills Program. For the systematic analysis, the following data were extracted: (1) author, year, and study design; (2) participant characteristics; (3) type of PUP intervention; (4) EMG outcome measures; and (5) main results. For the meta-analysis, the EMG data of the SA and UT were calculated using the mean difference of EMG activity with a 95% confidence interval. DATA SYNTHESIS: Based on 19 studies with 356 participants, different hand positions (the distance between the hands, shoulder-flexion angle, and elbow-flexion angle) and different lower extremity positions variably affected the activation of the SA and UT during the PUP exercise. Also, when participants performed the PUP on an unstable surface compared with a stable surface, UT activity increased 2.74% (95% confidence interval = 0.07%, 5.41%). CONCLUSIONS: The standard PUP exercise elicited high EMG activity of the SA. Participants generated higher SA and lower UT EMG activity when they performed the PUP exercise on a stable surface in full elbow extension, with the hands placed shoulder-width apart, shoulder-flexion angles of 110° or 120°, and the ipsilateral lower extremity lifted.

A bioinspired hyperthermic macrophage-based polypyrrole-polyethylenimine (Ppy-PEI) nanocomplex carrier to prevent and disrupt thrombotic fibrin clots.

Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot prevention and reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs could be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to prevent and lyse fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments. STATEMENT OF SIGNIFICANCE: Fibrinolytic treatments for venous or arterial thrombotic syndromes using systemic administration of thrombolytics, such as streptokinase, can induce life-threatening bleeding complications. In this study, we offer the first proof of concept for a targeted photothermal fibrin clot reduction technology using macrophages loaded with polypyrrole-polyethylenimine nanocomplexes (Ppy-PEI NCs) and subjected to near-infrared radiation (NIR). We first show that the developed Ppy-PEI NCs can be taken up by defensive macrophages in vitro through endocytosis. The Ppy-PEI NCs generated local hyperthermia upon NIR treatment, which appeared to produce reactive oxygen species in Ppy-PEI NC-loaded macrophages. Preliminary evidence of efficacy as an antithrombotic tool is provided, in vitro, using fibrinogen-converted fibrin clots, and in vivo, in a rat femoral vascular thrombosis model generated by exposure to ferric chloride substance. The in vivo biocompatibility, photothermal behavior, biodistribution, and histological observation of cellular interactions with the Ppy-PEI NCs in the rat model provide rationale in support of further preclinical studies. This Ppy-PEI NC/NIR-based method, which uses a unique macrophage-guided targeting approach to disintegrate fibrin clots, may potentially overcome some of the disadvantages of current thrombolytic treatments.

A novel injectable in situ forming gel based on carboxymethyl hexanoyl chitosan/hyaluronic acid polymer blending for sustained release of berberine.

An in situ forming gel based on simply blending carboxymethyl hexanoyl chitosan (CHC) with low molecular weight hyaluronic acid (LMW HA) was developed, without needing cross-linking, photopolymerization or thermal treatments. The CHC/LMW HA blends formed nanoparticles and then rapidly transformed into supermolecular hydrogels under stirring. The gel formation mechanism was examined by Förster resonance energy transfer (FRET). The gels were injectable, cytocompatible and biodegradable, and showed shape-persistent behavior and adhesive property. Berberine, an anti-apoptotic and anti-arthritis naturally occurring compound, was encapsulated within the CHC/LMW HA gels. The gels demonstrated a pH-responsive characteristic which were able to release berberine in a sustained manner at pH 6.0 (simulating inflamed arthritic articular cartilage) and the degradation rates were accelerated at pH 7.4 (simulating healed normal tissue). The berberine-loaded gels effectively protected chondrocytes against sodium nitroprusside-induced apoptosis. The gels may be potentially useful as an injectable system for intra-articular drug delivery and cartilage tissue engineering.

Tongue Pressure Sensing Array Integrated with a System-on-Chip Embedded in a Mandibular Advancement Splint.

Obstructive sleep apnea (OSA), which is caused by obstructions of the upper airway, is a syndrome with rising prevalence. Mandibular advancement splints (MAS) are oral appliances for potential treatment of OSA. This work proposes a highly-sensitive pressure sensing array integrated with a system-on-chip (SoC) embedded in a MAS. The device aims to measure tongue pressure distribution in order to determine the efficacy of the MAS for treating OSA. The flexible sensing array consists of an interdigital electrode pair array assembled with conductive polymer films and an SoC capable of retrieving/storing data during sleep, and transmitting data for analysis after sleep monitoring. The surfaces of the conductive polymer films were patterned with microdomed structures, which effectively increased the sensitivity and reduced the pressure sensing response time. The measured results also show that the crosstalk effect between the sensing elements of the array was negligible. The sensitivity of the sensing array changed minimally after the device was submerged in water for up to 100 h.

Development of nanocomposite scaffolds based on biomineralization of N,O-carboxymethyl chitosan/fucoidan conjugates for bone tissue engineering.

Bone tissue engineering holds great promise and clinical efficacy for the regeneration of bone defects. In this study, an amphoteric N,O-carboxymethyl chitosan (NOCC) and fucoidan (FD) were covalently cross-linked via an amidation reaction to synthesize NOCC/FD composite hydrogels. The hydrogels were lyophilized and then three-dimensional scaffolds with interconnected macropores were obtained. To enhance the mechanical properties and osteogenic activity, the NOCC/FD scaffolds were biomineralized for the growth of hydroxyapatite crystals. A comparative assessment of the structures, morphologies, and physical properties of the original and mineralized scaffolds were performed by SEM, EDS, X-ray diffraction and FT-IR analysis. FD regulated the growth of hydroxyapatite nanocrystallites (n-HAp) and thus the NOCC/FD scaffolds showed better mineralization efficiency than NOCC scaffolds. The compressive strength of the scaffolds was greatly enhanced after mineralization with n-HAp. The n-HAp/NOCC/FD scaffolds enhanced the proliferation, ALP activity, and mineralization of osteoblast cells more strongly than the original and mineralized NOCC scaffolds. Hence, the n-HAp-mineralized NOCC/FD scaffolds may prove to be an excellent and versatile scaffold for bone tissue engineering.

A Wireless Monitoring System Using a Tunneling Sensor Array in a Smart Oral Appliance for Sleep Apnea Treatment.

Sleep apnea is a serious sleep disorder, and the most common type is obstructive sleep apnea (OSA). Untreated OSA will cause lots of potential health problems. Oral appliance therapy is an effective and popular approach for OSA treatment, but making a perfect fit for each patient is time-consuming and decreases its efficiency considerably. This paper proposes a System-on-a-Chip (SoC) enabled sleep monitoring system in a smart oral appliance, which is capable of intelligently collecting the physiological data about tongue movement through the whole therapy. A tunneling sensor array with an ultra-high sensitivity is incorporated to accurately detect the subtle pressure from the tongue. When the device is placed on the wireless platform, the temporary stored data will be retrieved and wirelessly transmitted to personal computers and cloud storages. The battery will be recharged by harvesting external RF power from the platform. A compact prototype module, whose size is 4.5 × 2.5 × 0.9 cm³, is implemented and embedded inside the oral appliance to demonstrate the tongue movement detection in continuous time frames. The functions of this design are verified by the presented measurement results. This design aims to increase efficiency and make it a total solution for OSA treatment.

Temperature/pH/Enzyme Triple-Responsive Cationic Protein/PAA-b-PNIPAAm Nanogels for Controlled Anticancer Drug and Photosensitizer Delivery against Multidrug Resistant Breast Cancer Cells.

The tumor microenvironments are often acidic and overexpress specific enzymes. In this work, we synthesized a poly(AA-b-NIPAAm) copolymer (PAA-b-PNIPAAm) using a reversible addition-fragmentation chain transfer (RAFT) polymerization method. PAA-b-PNIPAAm and a cationic protein (protamine) were self-assembled into nanogels, which effectively reduced the cytotoxicity of protamine. The protamine/PAA-b-PNIPAAm nanogels were responsive to the stimuli including temperature, pH, and enzyme due to disaggregation of PAA-b-PNIPAAm, change in random coil/α-helix conformation of protamine, and enzymatic hydrolysis of the protein. Changing the pH from 7.4 to a lowered pHe (6.5-5.0) resulted in an increase in mean particle size and smartly converted surface charge from negative to positive. The cationic nanogels easily passed through the cell membrane and enhanced intracellular localization and accumulation of doxorubicin-loaded nanogels in multidrug resistant MCF-7/ADR breast cancer cells. Cold shock treatment triggered rapid intracellular release of doxorubicin against P-glycoprotein (Pgp)-mediated drug efflux, showing significantly improved anticancer efficacy as compared with free DOX. Furthermore, the nanogels were able to carry a rose bengal photosensitizer and caused significant damage to the multidrug resistant cancer cells under irradiation. The cationic nanogels with stimuli-responsive properties show promise as drug carrier for chemotherapy and photodynamic therapy against cancers.

Self-Targeting, Immune Transparent Plasma Protein Coated Nanocomplex for Noninvasive Photothermal Anticancer Therapy.

Cancer cells exhibit specific physiological differences compared to normal cells. Most surface membranes of cancer cells are characterized by high expression of given protein receptors, such as albumin, transferrin, and growth factors that are also present in the plasma of patients themselves, but are lacking on the surface of normal cells. These distinct features between cancer and normal cells can serve as a niche for developing specific treatment strategies. Near-infrared (NIR)-light-triggered therapy platforms are an interesting novel avenue for use in clinical nanomedicine. As a photothermal agent, conducting polymer nanoparticles, such as polypyrrole (PPy), of great NIR light photothermal effects and good biocompatibility, show promising applications in cancer treatments through the hyperthermia mechanism. Autologous plasma proteins coated PPy nanoparticles for hyperthermia therapy as a novel core technology platform to treat cancers through secreted protein acid and rich in cysteine targeting are developed here. This approach can provide unique features of specific targeting toward cancer cell surface markers and immune transparency to avoid recognition and attack by defense cells and achieve prolonged circulation half-life. This technology platform unveils new clinical options for treatment of cancer patients, supporting the emergence of innovative clinical products.

Development of genipin-crosslinked fucoidan/chitosan-N-arginine nanogels for preventing Helicobacter infection.

AIM: This study aims to validate the anti-Helicobacter pylori efficacy of amoxicillin-loaded nanoparticles and nanogels with pH-responsive and site-specific drug release properties against H. pylori infection. MATERIALS & METHODS: Genipin-crosslinked low molecular weight fucoidan/chitosan-N-arginine nanogels (FCSA) were prepared for targeted delivery of amoxicillin to the site of H. pylori infected AGS gastric epithelial cells. RESULTS: The negatively charged nanogels (n-FCSA) adhered to H. pylori and exhibited pH-responsive drug release property to reduce cytotoxic effects in H. pylori infected AGS cells. CONCLUSION: These in vitro findings suggest that n-FCSA nanogels are potential carriers for H. pylori specific delivery of antibacterial agents, and provide the basis for further studies on the clinical use of the nanogels.