Combined metabolome and transcriptome analysis reveals a critical role of lignin biosynthesis and lignification in stem-like pneumatophore development of the mangrove Avicennia marina.

MAIN CONCLUSION: Transcriptional and metabolic regulation of lignin biosynthesis and lignification plays crucial roles in Avicennia marina pneumatophore development, facilitating its adaptation to coastal habitats. Avicennia marina is a pioneer mangrove species in coastal wetland. To cope with the periodic intertidal flooding and hypoxia environment, this species has developed a complex and extensive root system, with its most unique feature being a pneumatophore with a distinct above- and below-ground morphology and vascular structure. However, the characteristics of pneumatophore lignification remain unknown. Studies comparing the anatomy among above-ground pneumatophore, below-ground pneumatophore, and feeding root have suggested that vascular structure development in the pneumatophore is more like the development of a stem than of a root. Metabolome and transcriptome analysis illustrated that the accumulation of syringyl (S) and guaiacyl (G) units in the pneumatophore plays a critical role in lignification of the stem-like structure. Fourteen differentially accumulated metabolites (DAMs) and 10 differentially expressed genes involved in the lignin biosynthesis pathway were targeted. To identify genes significantly associated with lignification, we analyzed the correlation between 14 genes and 8 metabolites and further built a co-expression network between 10 transcription factors (TFs), including 5 for each of MYB and NAC, and 23 enzyme-coding genes involved in lignin biosynthesis. 4-Coumarate-CoA ligase, shikimate/quinate hydroxycinnamoyl transferase, cinnamyl alcohol dehydrogenase, caffeic acid 3-O-methyltransferase, phenylalanine ammonia-lyase, and peroxidase were identified to be strongly correlated with these TFs. Finally, we examined 9 key candidate genes through quantitative real-time PCR to validate the reliability of transcriptome data. Together, our metabolome and transcriptome findings reveal that lignin biosynthesis and lignification regulate pneumatophore development in the mangrove species A. marina and facilitate its adaptation to coastal habitats.

Fasciculation differences between ALS and non-ALS patients: an ultrasound study.

BACKGROUND: Fasciculation is an important sign for the diagnosis of amyotrophic lateral sclerosis (ALS). Our study aimed to analyze the difference in fasciculation detected with muscle ultrasonography (MUS) between ALS patients and non-ALS patients with symptoms resembling ALS. METHODS: Eighty-eight ALS patients and fifty-four non-ALS (eight multifocal motor neuropathy, 32 chronic inflammatory demyelinating polyneuropathy/Charcot-Marie-Tooth, and 14 cervical spondylopathy or lumbar spondylopathy) patients were recruited. MUS was performed on 19 muscle groups in cervical, lumbosacral, bulbar, and thoracic regions for each patient. The intensity of fasciculation was divided into five grades based on firing frequency and number in the involved muscle groups. RESULTS: The overall detection rates were 72.8% in ALS and 18% in non-ALS patients. The fasciculation grades (median [IQR]) were 2 (0-3) in ALS and 0 (0-0) in non-ALS patients (P < 0.001). Fasciculations were observed in four regions for ALS patients and primarily distributed in proximal limbs. Fasciculations in non-ALS patients were primarily low-grade and mostly distributed in distal limbs. DISCUSSION: The fasciculation grade was higher in ALS than non-ALS patients. The distribution pattern of fasciculation was different between ALS and non-ALS patients. CONCLUSIONS: The fasciculation grade and distribution pattern detected with MUS could help distinguish ALS from non-ALS patients.

Organic Electrochemical Transistor for in Situ Detection of H2O2 Released from Adherent Cells and Its Application in Evaluating the In Vitro Cytotoxicity of Nanomaterial.

Detection of hydrogen peroxide (H2O2) produced by living cells is very significant to fully understand its roles in cellular physiology, as well as providing reliable diagnosis of pathological conditions. However, in situ detection of H2O2 released from adherent cells in cellular culture medium is still insufficiently achieved. Here, we report an electrochemical platform for in situ detection of H2O2 produced by adherent cells in cellular culture medium. It is based on the use of organic electrochemical transistor (OECT) fabricated on a flexible poly(ethylene terephthalate) substrate and Transwell support. A screen-printed carbon paste electrode was modified with carbon nanotubes and platinum nanoparticles and served as the gate of the device. Under optimal conditions, this device exhibits good modulation and sensitivity. It works in the 0.5 µM to 0.1 mM H2O2 concentration range and has a 0.2 µM detection limit. The cells were seeded and grew on the Transwell membrane. Upon being stimulated by N-formylmethionyl-leucyl-phenylalanine peptide, H2O2 produced by the adherent cells diffused into the bottom chamber of the Transwell and was in situ detected by OECT. Moreover, evaluating in vitro cytotoxicity of the nanomaterial using the OECT-Transwell platform was realized. This simple electrochemical platform would be of great interest for in vitro cytotoxicity, cellular physiology study, and diagnosis of pathological conditions.

Anti-BCMA CAR-T therapy for multiple myeloma with extramedullary disease: A case report and review of the literature.

INTRODUCTION: Multiple myeloma (MM) with extramedullary disease (EMD) is rare in clinical practice, and B cell maturation antigen (BCMA) CAR-T cell therapy is a novel therapy for hematologic malignancies. Very few reports have been published on the effect of CAR-T-cell therapy in MM with EMD. Here, we report a case of MM with extramedullary lesions treated with BCMA CAR-T therapy. CASE PRESENTATION: A 66-year-old female patient presented to our hospital with an enlarged left maxillary gingiva. DIAGNOSIS: Diagnosis of indolent MM stage III (DS staging) and stage III (ISS and R ISS) with extramedullary lesions. INTERVENTION: The patient underwent a clinical trial of humanized anti-BCMA CAR T cell therapy. RESULTS: Symptoms improved; left gingival hyperplasia and swelling resolved; left buccal mass resolved; and neck and submandibular masses resolved. Pathological examination of the exfoliated masses showed necrotic tissue. CONCLUSION: MM with extramedullary lesions often has limited treatment options, and traditional chemotherapy methods are ineffective; however, BCMA CAR-T cell therapy can significantly improve the symptoms of extramedullary lesions in MM.

Comparison of bleomycin polidocanol foam vs electrochemotherapy combined with polidocanol foam for treatment of venous malformations.

OBJECTIVE: This study aims to investigate the difference in safety and efficacy between two treatments for venous malformations (VMs), electrochemotherapy combined with polidocanol foam (ECP) and bleomycin polidocanol foam (BPF), providing alternative therapies for VMs. METHODS: We conducted a retrospective review of 152 patients with VMs treated with ECP and BPF. Pre- and post-treatment magnetic resonance images (MRIs) were collected, and clinical follow-up assessments were performed. Imaging results were used to calculate lesion volume changes. Clinical outcomes included changes in pain and improvements in perceived swelling. Patients were followed up at 1 week and 6 months after surgery. All emerging complications were documented in detail. RESULTS: Of the 152 patients, 87 (57.2%) received BPF treatment, and 65 (42.8%) received ECP treatment. The most common location of VMs was the lower extremities (92/152; 60.2%), and the most common symptom was pain (108/152; 71.1%). Forty-three patients had previously undergone therapy in the BPF group (43/87; 49.4%), whereas 30 patients had received prior treatment in the ECP group (30/65; 46.2%). The study found that the percentage of lesion volume reduction in the BPF group was not significantly different from that in the ECP group (75.00% ± 17.85% vs 74.69% ± 8.48%; P = .899). ECP was more effective when the initial lesion volume was greater than 30 mL (67.66% ± 12.34% vs 73.47% ± 8.00%; P = .048). Patients treated with BPF had significantly less posttreatment pain than those treated with ECP, in different baseline lesion size. In the overall sample, pain relief was significantly higher in the BPF group than in the ECP group (4.21 ± 1.19 vs 3.57 ± 0.76; P = .002). However, there was no difference in pain relief between the two groups for the treatment of initially large VMs (4.20 ± 0.94 vs 3.70 ± 0.87; P = .113). The ECP group was significantly more likely to develop hyperpigmentation (5/87; 5.75% vs 11/65; 16.92%; P = .026) and swelling (9/87; 10.34% vs 16/65; 24.62%; P = .019) 1 week after surgery than the BPF group. CONCLUSIONS: Our study demonstrates that both BPF and ECP are effective treatments for VMs, with BPF being a safer option. ECP is a better choice for patients with the initial lesion volume greater than 30 mL, but it is more likely to lead to early swelling and hyperpigmentation.

Clinical outcomes and predictors of bleomycin polidocanol foam sclerotherapy treatment response in venous malformations.

OBJECTIVE: To evaluate the safety and efficacy of bleomycin polidocanol foam (BPF) sclerotherapy for venous malformations (VMs) and analyze the associated clinical outcomes and predictors. METHODS: We retrospectively assessed BPF sclerotherapy outcomes in 138 patients with VMs. We analyzed pain levels, lesion volume reduction, and subjective perception of response. Logistic regression analysis was performed to identify potential predictors of treatment outcome. Additionally, we carefully monitored and recorded complications. RESULTS: There was a notable average reduction in lesion volume by 78.50% ± 15.71%. The pain numerical rating scale (NRS) score decreased from 4.17 ± 2.63 prior to treatment to 1.05 ± 1.54 afterward, and 70.3% of the patients experienced effective relief after a single BPF treatment. Multivariate analysis revealed that a high baseline NRS (odds ratio [OR]: 4.026) and elevated activated partial thromboplastin time (APTT, OR: 1.200) were positive predictors of pain reduction. Additionally, a high baseline NRS score (OR: 1.992) and elevated thrombocytocrit (PCT, OR: 2.543) were positive predictors of incomplete postoperative pain relief. Minor complications occurred in 31 (22.46%) patients. CONCLUSION: BPF sclerotherapy is safe and effective for VMs, resulting in significant reduction in lesion volume, improved symptoms, and minimal complications. APTT and PCT levels are important predictors of pain outcomes following BPF treatment.

cxcl12a plays an essential role in pharyngeal cartilage development.

Background: Neural crest cells constitute a distinct set of multipotent cells that undergo migration along predefined pathways, culmination in the differentiation into a plethora of cell types, including components of the pharyngeal cartilage. The neurocranium is composite structure derived from both cranial neural crest and mesoderm cells, whereas the pharyngeal skeletal elements-including the mandibular and branchial arches-are exclusively formed by craniofacial neural crest cells. Previous studies have elucidated the critical involvement of the chemokine signaling axis Cxcl12b/Cxcr4a in craniofacial development in zebrafish (Danio rerio). Nonetheless, the function contribution of Cxcl12a and Cxcr4b-the homologous counterparts of Cxcl12b and Cxcr4a-remain largely unexplored. Methods: In the present study, mutant lines for cxcl12a and cxcr4b were generated employing CRISPR/Cas9 system. Temporal and spatial expression patterns of specific genes were assessed using in situ hybridization and dual-color fluorescence in situ hybridization techniques. High-resolution confocal microscopy was utilized for in vivo imaging to detect the pharyngeal arch or pouch patterning. Additionally, cartilage formation within the craniofacial region was analyzed via Alcian blue staining, and the proliferation and apoptosis rates of craniofacial neural crest cells were quantified through BrdU incorporation and TUNEL staining. Results: Our data reveals that the deletion of the chemokine gene cxcl12a results in a marked diminution of pharyngeal cartilage elements, attributable to compromised proliferation of post-migratory craniofacial neural crest cells. Subsequent experiments confirmed that Cxcl12a and Cxcl12b exhibit a synergistic influence on pharyngeal arch and pouch formation. Conclusion: Collectively, the present investigation furnishes compelling empirical evidence supporting the indispensable role of Cxcl2a in craniofacial cartilage morphogenesis, albeit cxcr4b mutants exert a minimal impact on this biological process. We delineate that Cxcl12a is essential for chondrogenesis in zebrafish, primarily by promoting the proliferation of craniofacial neural crest cells. Furthermore, we proposed a conceptual framework wherein Cxcl12a and Cxcl12b function synergistically in orchestrating both the pharyngeal arch and pouch morphogenesis.

Reference values for lower limb nerve ultrasound and its diagnostic sensitivity.

We aimed to establish the cross-sectional area (CSA) reference values for peripheral nerves of lower extremities in a healthy Chinese population, and to determine their diagnostic values for chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Charcot-Marie-Tooth disease type1A (CMT1A). One hundred eleven healthy subjects, 15-70 years of age, as well as 104 CIDP patients and 26 CMT1A patients were recruited. CSA at predetermined sites of the tibial, fibular, sciatic and sural nerves was measured. The CSA of the tibial nerve ranged from 10.2 ± 1.9 to 20.7 ± 3.6 mm2, and for fibular nerve from 8.4 ± 1.8 to 9.5 ± 1.9 mm2. 86% CIDP patients had upper limb nerve enlargement, while only 67% had lower limb nerve enlargement. In CIDP patients with normal upper limb ultrasound, 56% (5/9) would have lower limb nerve enlargement. All CMT1A patients had both upper and lower limb nerve enlargement. Addition of lower limb nerve ultrasound showed no added value in diagnosis of CMT1A, but could be supplementary for CIDP when upper limb ultrasound is normal.

Acellular fish skin enhances wound healing by promoting angiogenesis and collagen deposition.

Acellular matrix is a type of promising biomaterial for wound healing promotion. Although acellular bovine and porcine tissues have proven effective, religious restrictions and risks of disease transmission remain barriers to their clinical use. Acellular fish skin (AFS), given its similarity to human skin structure and without the aforementioned disadvantages, is thus seen as an attractive alternative. This study aims to fabricate AFS from the skin of black carp (Mylopharyngodon piceus), evaluate its physical and mechanical properties and assess its impact on wound healing. The results showed that AFS has a highly porous structure, along with high levels of hydrophilicity, water-absorption property and permeability. Furthermore, physical characterization showed the high tensile strength of AFS in dry and wet states, and high stitch tear resistance, indicating great potential in clinical applications. Cell Counting Kit-8 was used to test the viability of L929 cells when culturing in the extracts of AFS. Compared with the control group, there is no significant difference in optical density value when culturing in the extracts of AFS at days 1, 3 and 7 (*p> 0.05).In vivowound healing evaluation then highlighted its promotion of angiogenesis and collagen synthesis, its function in anti-inflammation and acceleration in wound healing. Therefore, this study suggests that AFS has potential as a promising alternative to mammal-derived or traditional wound dressing.

Influence of polymer addition on the amorphization, dissolution and physical stability of co-amorphous systems.

Co-amorphous systems have been developed to address the solubility challenge of poorly-water soluble drugs. However, the dissolution rate of co-amorphous systems can be too fast in some cases, causing super-saturation, followed by precipitation and thereafter loss of the advantage. In this study, hydroxypropyl methylcellulose (HPMC) was co-formulated at 10% (w/w) with carvedilol-L-aspartic acid (CAR-ASP) co-amorphous systems at CAR to ASP molar ratios of 1:1, 1:1.5 and 1:2. No obvious changes of glass transition temperatures (Tgs) were detected for CAR-ASP 1:1.5-HPMC and CAR-ASP 1:2-HPMC compared to the corresponding co-amorphous systems, whilst CAR-ASP 1:1-HPMC showed an increased Tg (88.9 ± 1.3 °C) compared to CAR-ASP 1:1 (80.2 ± 0.9 °C). HPMC was involved in the molecular interactions of the CAR-ASP-HPMC systems, but did not disturb ionic interactions between CAR and ASP. Addition of HPMC optimized the dissolution of the CAR-ASP systems by reducing the initial dissolution rate and maintaining super-saturation for a longer period. No negative effect of HPMC addition on physical stability was observed at 25 °C and 40 °C under dry conditions for 7 months. Therefore, it appears promising to co-formulate a small amount of polymer with co-amorphous systems to achieve optimized dissolution characteristics while maintaining the desired physical stability.

Implantation of Foldable Capsular Vitreous Body for the Treatment of Acute Retinal Necrosis Syndrome: A Case Report.

The authors present the case of a 35-year-old male who was diagnosed with acute retinal necrosis syndrome that evolved into retinal detachment (RD), even after immediate treatment with systemic antiviral medications, as well as intravitreal injection and laser photocoagulation. Pars plana vitrectomy plus silicone oil tamponade was performed, but silicone oil emulsified 22 months later. Due to the widespread necrosis lesions and defects of the peripheral retina, RD was highly likely to reoccur after silicone oil removal; thus, foldable capsular vitreous body was implanted to support the retina. No recurrent RD was observed afterward. [Ophthalmic Surg Lasers Imaging Retina. 2020;51:653-657.].

Sorafenib-Loaded Nanoparticles Based on Biodegradable Dendritic Polymers for Enhanced Therapy of Hepatocellular Carcinoma.

PURPOSE: In spite of its enhanced efficacy and reduced side effects in clinical hepatocellular carcinoma (HCC) therapy, the therapeutic efficacy of antitumor angiogenesis inhibitor sorafenib (SFB) is still restricted due to short in vivo half-life and drug resistance. Here, a novel SFB-loaded dendritic polymeric nanoparticle (NP-TPGS-SFB) was developed for enhanced therapy of HCC. METHODS: NP-TPGS-SFB was fabricated by encapsulating SFB with biodegradable dendritic polymers poly(amidoamine)-poly(γ-benzyl-L-Glutamate)-b-D-α-tocopheryl polyethylene glycol 1000 succinate (PAM-PBLG-b-TPGS). RESULTS: NP-TPGS-SFB exhibited excellent stability and achieved acid-responsive release of SFB. It also exhibited much higher cellular uptake efficiency in HepG2 human liver cells than PEG-conjugated NP (NP-PEG-SFB). Furthermore, MTT assay confirmed that NP-TPGS-SFB induced higher cytotoxicity than NP-PEG-SFB and free SFB, respectively. Lastly, NP-TPGS-SFB significantly inhibited tumor growth in mice bearing HepG2 xenografts, with negligible side effects. CONCLUSION: Our result suggests that NP-TPGS-SFB may be a novel approach for enhanced therapy of HCC with promising potential.

Vagus Nerve Ultrasound in Chronic Inflammatory Demyelinating Polyradiculoneuropathy and Charcot-Marie-Tooth Disease Type 1A.

BACKGROUND AND PURPOSE: Both clinical autonomic dysfunction and involvement of autonomic nerves have been reported in a range of peripheral nerve disorders. We employed nerve ultrasound to assess the size of the vagus nerve in a serial study of patients with chronic inflammatory demyelinating polyradiculoneuropathy (CIDP) and Charcot-Marie-Tooth type 1B (CMT1B) as compared to healthy controls (HCs). We correlated these findings with involvement of the median and ulnar nerves. METHODS: Forty-three patients with CIDP, 8 with CMT1A, and 105 HC were prospectively recruited. The cross-sectional areas (CSAs) of the vagus, median, and ulnar nerves were measured bilaterally. The alteration of CSA of those nerves was followed longitudinally in CIDP. RESULTS: The median (range) CSA of the vagus nerve was 2 (1-28) mm2 in CIDP, 3 (2-6) mm2 in CMT1A, and 1 (1-2) mm2 in HC. The vagus nerve CSA was positively correlated with the maximum CSA of median/ulnar nerve in CIDP and CMT1A. The alteration in vagus nerve CSA was positively correlated with the alteration in mean median/ulnar nerve CSA in CIDP during follow-up. CONCLUSIONS: The vagus nerve was involved to a similar extent as the median and ulnar nerves in CIDP and CMT1A, although no symptoms or signs of vagus nerve involvement were found. Further study should be performed to explore the clinical relevance of vagus nerve enlargement in these disorders.

Comparative Study of 660 and 830 nm Photobiomodulation in Promoting Orthodontic Tooth Movement.

Objective: Photobiomodulation (PBM) can usefully promote wound healing and relieve pain via its biological effects, with a wide range of applications in clinical medicine. The aim of the present study was to investigate the effect of 660 and 830 nm PBM on orthodontic tooth movement. Background data: PBM is based on the biological effects of diode laser irradiation on tissues, promoting cell proliferation and activity. Materials and methods: An orthodontic force was applied to the upper right first molars exposed to a 660 and 830 nm PBM (LHH-500I; Beijing Long Hui Heng Medical Science and Technology Development Corporation) on days 0, 1, 2, 3, 4, 5, and 7 for 50 sec with power density of 0.1 W/cm2 (a beam area of 0.5 cm2, radiate power of 0.05 W), energy density of 5 J/cm2 within 14 days, and a control group with no laser irradiation. Tooth movement was analyzed using a stereomicroscope, the number of osteoclasts determined by tartrate-resistant acid phosphatase (TRAP), and the expression of bone remodeling factors evaluated by immunohistochemistry. Results: The expression of IL-1ß, RANKL, and OPG was significantly stimulated in the 660 and 830 nm groups. The expression of RANKL was significantly higher in the 660 nm group than in the 830 nm group on days 5 and 7; however, there was no significant difference in the expression of OPG and IL-1ß between the 660 and 830 nm groups on days 1, 2, 3, 4, 5, 7, and 14. On days 3 and 5, the number of osteoclasts in the 660 nm group was higher than that in the 830 nm group, and the difference was statistically significant. Tooth movement over 14 days was significantly higher in the 660 and 830 nm groups than in the control group, and there was no significant difference between the 660 and 830 nm groups finally. Conclusions: Both 660 and 830 nm can accelerate the orthodontic tooth movement and promote alveolar bone remodeling on the compression side. Although the difference of tooth movement over 14 days between the two groups was not statistically significant; however, 660 nm PBM to accelerate bone remodeling is stronger than 830 nm PBM at an early stage.

SS-mPEG chemical modification of recombinant phospholipase C for enhanced thermal stability and catalytic efficiency.

PEGylation is one of the most promising and extensively studied strategies for improving the properties of proteins as well as enzymic physical and thermal stability. Phospholipase C, hydrolyzing the phospholipids offers tremendous applications in diverse fields. However, the poor thermal stability and higher cost of production have restricted its industrial application. This study focused on improving the stabilization of recombinant PLC by chemical modification with methoxypolyethylene glycol-Succinimidyl Succinate (SS-mPEG, MW 5000). PLC gene from isolate Bacillus cereus HSL3 was fused with SUMO, a novel small ubiquitin-related modifier expression vector and over expressed in Escherichia coli. The soluble fraction of SUMO-PLC reached 80% of the total recombinant protein. The enzyme exhibited maximum catalytic activity at 80 °C and was relatively thermostable at 40-70 °C. It showed extensive substrate specificity pattern and marked activity toward phosphatidylcholine, which made it a typical non-specific PLC for industrial purpose. SS-mPEG-PLC complex exhibited an enhanced thermal stability at 70-80 °C and the catalytic efficiency (Kcat/Km) had increased by 3.03 folds compared with free PLC. CD spectrum of SS-mPEG-PLC indicated a possible enzyme aggregation after chemical modification, which contributed to the higher thermostability of SS-mPEG-PLC. The increase of antiparallel ß sheets in secondary structure also made it more stable than parallel ß sheets. The presence of SS-mPEG chains on the enzyme molecule surface somewhat changed the binding rate of the substrates, leading to a significant improvement in catalytic efficiency. This study provided an insight into the addition of SS-mPEG for enhancing the industrial applications of phospholipase C at higher temperature.

Putting a finger on the problem: Finger stick blood draw and immunization at the well-child exam elicit a cortisol response to stress among one-year-old children.

Research examining stress reactivity of the hypothalamic-pituitary-adrenocortical (HPA) axis in young children has historically been hampered by a lack of reliable methods to invoke a cortisol stress response. This report details an effective method of eliciting a cortisol rise in one-year-old children (N = 83) by modifying and combining two naturalistic stressors previously used with infants and children. Salivary cortisol levels were collected from children before and after a finger stick blood draw and immunizations performed during their one year well-child checkup at their pediatrician's office. Results indicated that the stressor was successful at eliciting a significant cortisol response. An extensive set of potential demographic and clinical confounds were also assessed in order to identify methodological considerations important in studies of infant cortisol. The stress paradigm presented here provides a promising alternative for studies of infant HPA activity to enable investigators to more effectively evaluate early functioning of the biological stress system during this developmentally important life stage.

A spermine conjugated stearic acid-g-chitosan oligosaccharide polymer with different types of amino groups for efficient p53 gene therapy.

The effect of various amino groups on gene vector is different. In order to combine their effect in one vector and finally promote the transfection efficiency, a biogenic tetra-amine spermine was introduced to modify the stearic acid-grafted chitosan oligosaccharide (CSOSA) polymer to build a new gene delivery system. The spermine linked CSOSA (SP-CSOSA) polymer consists two types of amino groups with 73.3%, 19.3% of all nitrogen atoms for primary and secondary amine groups, respectively. The SP modified CSOSA showed strong DNA condensation capability and obviously enhanced proton binding ability especially at about pH 5.0, which significantly promoted the escape of SP-CSOSA/pDNA complexes from endo-lysosoms. Moreover, the transfection efficiency at the N/P ratio of 10 could compete with that of Lipofectamine 2000 and PEI 25K, but with lower cytotoxicities. The therapeutic wild type p53 gene transfected by the SP-CSOSA polymer restored the function of aberrant p53 gene and induced obvious cell apoptosis and G1 phase arrest. We concluded that the new vector SP-CSOSA polymer proved to be a potential delivery system for gene therapy.

Multi-cycle chemotherapy with the glycolipid-like polymeric micelles evade cancer stem cell enrichment in breast cancer therapy.

Multi-cycle chemotherapy is commonly used in the clinic, while the phenomena of enrichment of cancer stem cells (CSCs) and enhanced multi-drug resistance (MDR) are commonly involved. This research was designed for evaluating this successive administration. Chitosan oligosaccharide-g-stearic acid (CSOSA) polymer was used as the drug delivery system (DDS) to perform tri-cycle chemotherapy on a new tumor model induced by mammosphere cells. In vitro, on CSCs enriched mammospheres model, the doxorubicin-loaded CSOSA (CSOSA/DOX) displayed an improved growth inhibition effect measured by acid phosphatase assay (APH). While in vivo, the CSOSA/DOX micelles blocked tumor progression and led to a marked decrease of CSCs proportion as well as MDR capacity. What's more, the CSOSA/DOX helped decay the microenvironment and attenuate systemic side effects. We concluded that the CSOSA polymer could be a potential DDS for long-term multi-cycle chemotherapy in antitumor research.