Can a single-port robot be safely used for robotic total gastrectomy for advanced gastric cancer? First experience using the da Vinci SP platform.

Background: Many studies have shown the operative feasibility and safety of robotic gastrectomy. Surgeons are pursuing single-port (SP) surgery to leverage the advantages of minimally invasive gastrectomy. The purpose of this study was to describe technical considerations and short-term outcomes from the first reported SP robotic total gastrectomy (RTG) using the da Vinci SP platform. Methods: A 75-year-old patient with a body-mass index of 19.8 kg/m2 and clinical stage III cancer (cT3N+M0) underwent SP RTG on 22 January 2022 at the Department of General Surgery, the Chinese PLA General Hospital. All procedures were performed successfully using the da Vinci SP robotic platform. Results: The SP RTG was successfully performed with D2 lymphadenectomy including No. 10 lymph-nodes dissection and extracorporeal Roux-en-Y anastomosis. Except for subcutaneous emphysema, no severe adverse events occurred during the operation. According to a visual analogue scale (VAS), the subjective feeling of post-operative pain was given a VAS score of 3 of 10 on Post-Operative Day 1 (POD 1), 1 of 10 on POD 3, and 1 of 10 on POD 7. We removed the gastric tube on POD 2 and advised sipping water, a liquid diet, and a soft diet on PODs 2, 4, and 6, respectively. The patient was discharged without any complications on POD 8. Conclusion: RTG is technically feasible and safe using the da Vinci SP robotic platform. To our knowledge, this is the first study using the da Vinci SP platform in RTG for advanced gastric cancer in elderly patients. To verify its superior operative outcomes, further clinical trials are needed.

Inducing enantioselective crystallization with and self-assembly of star-shaped hybrid polymers prepared via "grafting to" strategy.

Helical polymers present some interesting and distinctive properties, and one of the most distinguished applications of them is the chiral recognition and resolution of enantiomers. In this work, star-shaped hybrid helical poly (phenyl isocyanide) (PPI) with polyhedral oligomeric silsesquioxanes (POSS) as the core was designed and synthesized by "grafting to" strategy. The homoarm star-shaped hybrid POSS-(PPI)8 was first obtained by the click reaction between azide-modified POSS (POSS-(N3 )8 ) and alkynyl-modified PPI (PPI-Alkynyl). The hybrid POSS-(PPI)8 was with predominated left-handed helical conformation and exhibited excellent ability in the enantioselective crystallization of racemic compounds. In the meantime, heteroarm star-shaped hybrid (PEG)4 -POSS-(PPI)4 was prepared by the click reaction of POSS-(N3 )8 with PPI-Alkynyl and alkynyl-modified poly (ethylene glycol) (PEG-Alkynyl). The hybrid (PEG)4 -POSS-(PPI)4 was amphiphilic, and it could self-assemble to form spherical micelles in aqueous solutions.

Could neoadjuvant chemotherapy increase postoperative complication risk of laparoscopic total gastrectomy? A mono-institutional propensity score-matched study in China.

BACKGROUND: The potential survival benefit of neoadjuvant chemotherapy (NC) in patients with advanced gastric cancer has been widely recognized. With the development of minimally invasive surgery, which is represented by laparoscopy, the effect of NC on the safety of laparoscopic gastrectomy remains to be further explored. AIM: To compare the short-term outcomes of laparoscopic total gastrectomy (LTG) after NC (NC-LTG) with LTG alone. METHODS: A total of 92 patients who underwent NC-LTG and 381 patients who received LTG alone at the Chinese PLA General Hospital between September 2015 and September 2020 were retrospectively included in our study. We used propensity-score matching (PSM) to balance baseline bias. After 1:1 PSM, 73 patients were included in each group with no statistically significant difference in baseline characteristics. RESULTS: The NC-LTG group exhibited a longer operation time (244.10 ± 48.13 min vs 225.74 ± 45.33 min, P = 0.019) and increased intraoperative blood loss [150 (100-300) mL vs 100 (100-200) mL, P = 0.011] compared to the LTG group. The 30-d postoperative morbidity of the NC-LTG group was 20.5% (15/73), and that of the LTG group was 13.7% (10/73). There were no significant differences in 30-d severe complication rates or anastomotic leakage rates. Subgroup analysis showed that the patients with pTNM (pathological tumor-node-metastasis classification) T0N0-II in the NC-LTG group underwent a longer operation than the LTG group, while no significant difference was found in any perioperative index for the pTNM III patients. A multivariate analysis showed that an operation time longer than 240 min was an independent risk factor (odds ratio = 3.021, 95% confidence interval: 1.160-7.868, P = 0.024), while NC was not an independent risk factor for postoperative complications in LTG. CONCLUSION: Despite a longer operation time and more blood loss after NC-LTG, which indicate surgical difficulty, NC-LTG exhibits acceptable short-term outcomes compared to LTG, suggesting the safety and feasibility of NC-LTG.

Leukemia inhibitory factor promotes gastric cancer cell proliferation, migration, and invasion via the LIFR-Hippo-YAP pathway.

The long-term outcome of gastric cancer (GC) patients remains unsatisfactory despite some recent improvements. Leukemia inhibitory factor (LIF) is a prognostic biomarker for some solid tumors, however its role in GC remains unknown. In this study, we demonstrated that LIF and LIF receptor (LIFR) are overexpressed in GC tissues and established that a correlation exists between them. LIF and LIFR expression are associated with tumor differentiation, lymphovascular invasion, tumor stage, lymph node metastasis, and pTNM stage, indicating that they may be useful prognostic factors. LIF promoted GC cell proliferation, colony formation, invasion, migration, and tumor growth; it also promoted cell cycle progression and inhibited apoptosis; and knocking out the LIFR gene reversed the effects of LIF. LIF inhibited the activity of the Hippo pathway, resulting in reduced phosphorylation of YAP, increased YAP nuclear translocation, and increased cell proliferation. Finally, silencing YAP mRNA expression suppressed cell proliferation. Overall, the results demonstrate that LIF promotes the malignant biological behavior of GC cells through LIFR-Hippo-YAP signaling. LIF may therefore be a useful biomarker for GC.

Establishment and validation of a nomogram to predict the risk of ovarian metastasis in gastric cancer: Based on a large cohort.

BACKGROUND: Ovarian metastasis is a special type of distant metastasis unique to female patients with gastric cancer. The pathogenesis of ovarian metastasis is incompletely understood, and the treatment options are controversial. Few studies have predicted the risk of ovarian metastasis. It is not clear which type of gastric cancer is more likely to metastasize to the ovary. A prediction model based on risk factors is needed to improve the rate of detection and diagnosis. AIM: To analyze risk factors of ovarian metastasis in female patients with gastric cancer and establish a nomogram to predict the probability of occurrence based on different clinicopathological features. METHODS: A retrospective cohort of 1696 female patients with gastric cancer between January 2006 and December 2017 were included in a single center, and patients with distant metastasis other than ovary and peritoneum metastasis were excluded. Potential risk factors for ovarian metastasis were analyzed using univariate and multivariable logistic regression. Independent risk factors were chosen to construct a nomogram which received internal validation. RESULTS: Ovarian metastasis occurred in 83 of 1696 female patients. Univariate analysis showed that age, Lauren type, whether the primary lesion contained signet-ring cells, vascular tumor emboli, T stage, N stage, the expression of estrogen receptor, the expression of progesterone receptor, serum carbohydrate antigen 125 and the neutrophil-to-lymphocyte ratio were risk factors for ovarian metastasis of gastric cancer (all P < 0.05). Multivariate analysis showed that age ≤ 50 years, Lauren typing of non-intestinal, gastric cancer lesions containing signet-ring cell components, N stage > N2, positive expression of estrogen receptor, serum carbohydrate antigen 125 > 35 U/mL, and a neutrophil-to-lymphocyte ratio > 2.16 were independent risk factors (all P < 0.05). The independent risk factors were constructed into a nomogram model using R language software. The consistency index after continuous correction was 0.840 [95% confidence interval: (0.774-0.906)]. After the internal self-sampling (Bootstrap) test, the calibration curve of the model was obtained with an average absolute error of 0.007. The receiver operating characteristic curve of the obtained model was drawn. The area under the curve was 0.867, the maximal Youden index was 0.613, the corresponding sensitivity was 0.794, and the specificity was 0.819. CONCLUSION: The nomogram model performed well in the prediction of ovarian metastasis. Attention should be paid to the possibility of ovarian metastasis in high-risk populations during re-examination, to ensure early detection and treatment.

Preoperative albumin levels predict prolonged postoperative ileus in gastrointestinal surgery.

BACKGROUND: Prolonged postoperative ileus (PPOI) is a prolonged state of "pathological" gastrointestinal (GI) tract dysmotility. There are relatively few studies examining the influence of preoperative nutritional status on the development of PPOI in patients who underwent GI surgery. The association between preoperative albumin and PPOI has not been fully studied. We hypothesized that preoperative albumin may be an independent indicator of PPOI. AIM: To analyze the role of preoperative albumin in predicting PPOI and to establish a nomogram for clinical risk evaluation. METHODS: Patients were drawn from a prospective hospital registry database of GI surgery. A total of 311 patients diagnosed with gastric or colorectal cancer between June 2016 and March 2017 were included. Potential predictors of PPOI were analyzed by univariate and multivariable logistic regression analyses, and a nomogram for quantifying the presence of PPOI was developed and internally validated. RESULTS: The overall PPOI rate was 21.54%. Advanced tumor stage and postoperative opioid analgesic administration were associated with PPOI. Preoperative albumin was an independent predictor of PPOI, and an optimal cutoff value of 39.15 was statistically calculated. After adjusting multiple variables, per unit or per SD increase in albumin resulted in a significant decrease in the incidence of PPOI of 8% (OR = 0.92, 95%CI: 0.85-1.00, P = 0.046) or 27% (OR = 0.73, 95%CI: 0.54-0.99, P = 0.046), respectively. Patients with a high level of preoperative albumin (≥ 39.15) tended to experience PPOI compared to those with low levels (< 39.15) (OR = 0.43, 95%CI: 0.24-0.78, P = 0.006). A nomogram for predicting PPOI was developed [area under the curve (AUC) = 0.741] and internally validated by bootstrap resampling (AUC = 0.725, 95%CI: 0.663-0.799). CONCLUSION: Preoperative albumin is an independent predictive factor of PPOI in patients who underwent GI surgery. The nomogram provided a model to screen for early indications in the clinical setting.

Nomogram to predict prolonged postoperative ileus after gastrectomy in gastric cancer.

BACKGROUND: Prolonged postoperative ileus (PPOI) is one of the common complications in gastric cancer patients who underwent gastrectomy. Evidence on the predictors of PPOI after gastrectomy is limited and few prediction models of nomogram are used to estimate the risk of PPOI. We hypothesized that a predictive nomogram can be used for clinical risk estimation of PPOI in gastric cancer patients. AIM: To investigate the risk factors for PPOI and establish a nomogram for clinical risk estimation. METHODS: Between June 2016 and March 2017, the data of 162 patients with gastrectomy were obtained from a prospective and observational registry database. Clinical data of patients who fulfilled the criteria were obtained. Univariate and multivariable logistic regression models were performed to detect the relationship between variables and PPOI. A nomogram for PPOI was developed and verified by bootstrap resampling. The calibration curve was employed to detect the concentricity between the model probability curve and ideal curve. The clinical usefulness of our model was evaluated using the net benefit curve. RESULTS: This study analyzed 14 potential variables of PPOI in 162 gastric cancer patients who underwent gastrectomy. The incidence of PPOI was 19.75% in patients with gastrectomy. Age older than 60 years, open surgery, advanced stage (III-IV), and postoperative use of opioid analgesic were independent risk factors for PPOI. We developed a simple and easy-to-use prediction nomogram of PPOI after gastrectomy. This nomogram had an excellent diagnostic performance [area under the curve (AUC) = 0.836, sensitivity = 84.4%, and specificity = 75.4%]. This nomogram was further validated by bootstrapping for 500 repetitions. The AUC of the bootstrap model was 0.832 (95%CI: 0.741-0.924). This model showed a good fitting and calibration and positive net benefits in decision curve analysis. CONCLUSION: We have developed a prediction nomogram of PPOI for gastric cancer. This novel nomogram might serve as an essential early warning sign of PPOI in gastric cancer patients.

[Schizophrenia-associated single nucleotide polymorphisms affecting microRNA function].

MicroRNAs (miRNAs) compose a class of non-coding transcripts with a mean length of 22 nucleotides, and play critical roles in regulating gene expression in the process of development, proliferation and differentiation of neurons. Recent genome-wide association studies (GWAS) find most of schizophrenia-associated single nucleotide polymorphisms (SNPs) locating in the non-coding regions, providing functional implications of miRNAs in the development of schizophrenia. In this review, we highlight the interplays between GWAS-SNPs and miRNAs in four perspectives: SNP in miRNA gene; miRNA located in the host gene; SNP located in the miRNA's seed sequence; SNP located in the miRNA's binding site. We also speculate on the future research on the role of miRNA in the development of schizophrenia.

Nanoscaled pearl powder accelerates wound repair and regeneration in vitro and in vivo.

Pearl powder has been used to treat many diseases like palpitations, insomnia, and epilepsy for thousands of years in Chinese medicine. It has demonstrated antioxidant, antiaging, antiradiative, and tonic activities. Pearl powder contains multiple active proteins, which are nutritious for skin cells and might be advantageous for wound repair and regeneration. However, its healing effect in vivo was not reported yet. This study aims to investigate the effects and the underlying mechanism of the pearl powders with different particle sizes in wound treatment. Briefly, the pearl powder with different sizes was characterized for their particle sizes and morphology. The protein release profiles of these powders were also studied. The influence of the different size of pearl powder in the proliferation, migration of skin cells was evaluated. Then, with the rat skin excision model, the effect of pearl powder on wound repair and regeneration was investigated. It was demonstrated that, all the micro and nanosized pearl powders could both increase the proliferation and migration of skin cells and accelerate the wound closure, as well as significantly enhanced the biomechanic strength of the healed skins. Moreover, the pearl powder treatment could improve the formation and regular deposition of collagen, and enhance the skin angiogenesis. Among all these in vitro and in vivo investigations, nanoscale pearl powder expressed the highest efficiency for healing. The mechanism might be contributed to the increased release of active proteins, enhanced tissue attachment, and the increased cellular uptake for the nano powder at the topical site.

Comparing PET/MRI with PET/CT for Pretreatment Staging of Gastric Cancer.

18F-FDG PET/MRI has been applied to the diagnosis and preoperative staging in various tumor types; however, reports using PET/MRI in gastric cancer are rare because of motion artifacts. We investigated the value of PET/MRI for preoperative staging compared with PET/CT in gastric cancer (GC). Thirty patients with confirmed GC underwent PET/CT and PET/MRI. TNM staging for each patient was determined from the PET/MRI and PET/CT images. The diagnostic performance of PET/MRI and PET/CT was calculated compared with the pathologic TNM stage. The two methods were compared using statistical analyses. The accuracy for T staging between PET/MRI and PET/CT was 76.9% vs. 57.7%, respectively. In T1 and T4a staging, the sensitivity and specificity for PET/MRI vs. PET/CT was 1.0 vs. 0.6 and 1.0 vs. 0.8, respectively. The area under the curve (AUC) for PET/MRI vs. PET/CT was 1.00 vs. 0.78 in the T1 stage, 0.73 vs. 0.66 in the T2 stage, 0.72 vs. 0.57 in the T3 stage, and 0.86 vs. 0.83 in the T4 stage. The accuracy for N staging of PET/MRI vs. PET/CT was 53.9% vs. 34.0%, and that for N0 vs. N+ was 85.0% vs. 77.0%. The sensitivity for PET/MRI in N3 staging was 0.67 and 0 for PET/CT. There was a statistically significant difference in the AUC for N1 staging (PET/MRI vs. PET/CT, 0.63 vs. 0.53, p = 0.03). SUVmax/ADC positively correlated with tumor volume and Ki-67. PET/MRI performs more accurately in TNM staging compared with PET/CT and is optimal for accurate N staging. SUVmax/ADC has positive correlations with tumor volume and Ki-67.

Predictive factors for lymph node metastasis and defining a subgroup treatable for laparoscopic lymph node dissection after endoscopic submucosal dissection in poorly differentiated early gastric cancer.

AIM: To investigate the predictive factors of lymph node metastasis (LNM) in poorly differentiated early gastric cancer (EGC); to guide the individual application of a combination of endoscopic submucosal dissection (ESD) and laparoscopic lymph node dissection (LLND) in a suitable subgroup of patients with poorly differentiated EGC. METHODS: We retrospectively analyzed 138 patients with poorly differentiated EGC who underwent gastrectomy with lymphadenectomy between January 1990 and December 2015. The association between the clinicopathological factors and the presence of LNM was retrospectively analyzed by univariate and multivariate logistic regression analyses. Odds ratios (OR) with 95% confidence interval (95%CI) were calculated. We further examined the relationship between the positive number of the significant predictive factors and the LNM rate. RESULTS: The tumor diameter (OR = 13.438, 95%CI: 1.773-25.673, P = 0.029), lymphatic vessel involvement (LVI) (OR = 38.521, 95%CI: 1.975-68.212, P = 0.015) and depth of invasion (OR = 14.981, 95%CI: 1.617-52.844, P = 0.024) were found to be independent risk factors for LNM by multivariate analysis. For the 138 patients diagnosed with poorly differentiated EGC, 21 (15.2%) had LNM. For patients with one, two and three of the risk factors, the LNM rates were 7.7%, 47.6% and 64.3%, respectively. LNM was not found in 77 patients that did not have one or more of the three risk factors. CONCLUSION: ESD might be sufficient treatment for intramucosal poorly differentiated EGC if the tumor is less than or equal to 2 cm in size and when LVI is absent upon postoperative histological examination. ESD with LLND may lead to the elimination of unnecessary gastrectomy in poorly differentiated EGC.

Timing of surgery after neoadjuvant chemotherapy for gastric cancer: Impact on outcomes.

AIM: To evaluate whether the neoadjuvant chemotherapy (NACT)-surgery interval time significantly impacts the pathological complete response (pCR) rate and long-term survival. METHODS: One hundred and seventy-six patients with gastric cancer undergoing NACT and a planned gastrectomy at the Chinese PLA General Hospital were selected from January 2011 to January 2017. Univariate and multivariable analyses were used to investigate the impact of NACT-surgery interval time (< 4 wk, 4-6 wk, and > 6 wk) on pCR rate and overall survival (OS). RESULTS: The NACT-surgery interval time and clinician T stage were independent predictors of pCR. The interval time > 6 wk was associated with a 74% higher odds of pCR as compared with an interval time of 4-6 wk (P = 0.044), while the odds ratio (OR) of clinical T3vs clinical T4 stage for pCR was 2.90 (95%CI: 1.04-8.01, P = 0.041). In Cox regression analysis of long-term survival, post-neoadjuvant therapy pathological N (ypN) stage significantly impacted OS (N0vs N3: HR = 0.16, 95%CI: 0.37-0.70, P = 0.015; N1vs N3: HR = 0.14, 95%CI: 0.02-0.81, P = 0.029) and disease-free survival (DFS) (N0vs N3: HR = 0.11, 95%CI: 0.24-0.52, P = 0.005; N1vs N3: HR = 0.17, 95%CI: 0.02-0.71, P = 0.020). The surgical procedure also had a positive impact on OS and DFS. The hazard ratio of distal gastrectomy vs total gastrectomy was 0.12 (95%CI: 0.33-0.42, P = 0.001) for OS, and 0.13 (95%CI: 0.36-0.44, P = 0.001) for DFS. CONCLUSION: The NACT-surgery interval time is associated with pCR but has no impact on survival, and an interval time > 6 wk has a relatively high odds of pCR.

[Mitochondrial drug delivery for cancer therapy].

Mitochondrion is one of the most vital organelles in cells of human body, and it is involved in many metabolic processes. Mitochondrion dysfunction is closely related to many diseases such as cancers, neurodegenerative diseases, obesity and ischemia reperfusion injury. As a result, mitochondrial drug delivery has gained more and more attention in the drug discovery against these diseases. This review gives a brief introduction to the relationship between mitochondria and human diseases(e.g., cancer), and summarizes the latest trend of mitochondrial targeting drug delivery system(MTDDS).

ß-Cyclodextrin-Linked Polyethylenimine Nanoparticles Facilitate Gene Transfer and Enhance the Angiogenic Capacity of Mesenchymal Stem Cells for Wound Repair and Regeneration.

Repair of deep wounds by cell transplantation strongly depends on angiogenesis and on the regeneration of skin and appendages. In this study, plasmid DNA encoding vascular endothelial growth factor-165 (VEGF-165) was transduced into bone-marrow mesenchymal stem cells (MSCs) using a nonviral vector, ß-cyclodextrin-linked polyethylenimine, to enhance angiogenic capacity. The effects of MSCs administered by intradermal injection or transplantation on wound closure were compared in a full-thickness excision wound model. The results showed that the MSC-seeded sponge had significantly stronger acceleration in wound closure than the MSC injection. The effects on wound repair and regeneration of transplanted MSCs and pDNA-VEGF1 65-transfected MSCs (TMSCs) with gelatin/ß-tricalcium phosphate scaffold were also investigated. Compared with MSC transplantation, TMSC transplantation showed higher efficacy in stimulating wound closure, promoting dermal collagen synthesis and regulating the deposition of newly formed collagen. In addition, the angiogenic capacity of the TMSCs was higher than that of the MSCs. The results indicate that the nonviral genetic engineering of the MSCs is a promising strategy to enhance the angiogenic capacity of MSCs for wound repair and angiogenesis. Functional gene-activated MSCs may be used as cost-effective and accessible seed cells for skin tissue engineering and as novel carriers for wound gene therapy.

Low-frequency sonophoresis enhances rivastigmine permeation in vitro and in vivo.

We investigated the enhancement effect of low-frequency sonophoresis on transdermal permeation of rivastigmine in vitro and in vivo. The in vitro permeation study showed that sonophoresis increased steady-state transdermal flux 0.31 ± 0.03 µg x cm(-2) x h(-1) and the extent of rivastigmine permeation 6.00 ± 0.56 µg x cm(-2) though excised skin (both P < 0.01). In the in vivo experiment, the C(max) 0.83 ± 0.16 µg x mL(-1) and AUC(0 --> 24 h) 12.35 ± 1.99 µg x h x mL(-1) of the sonophoresis group was also significantly higher than that of the control group (both P < 0.01). These data suggest that low-frequency sonophoresis could be an effective method to enhance rivastigmine permeation.

Sequential release of salidroside and paeonol from a nanosphere-hydrogel system inhibits ultraviolet B-induced melanogenesis in guinea pig skin.

Melanin is the one of most important pigments for skin color in mammals. Excessive biosynthesis of melanin induces various pigment disorders. Much effort has been made to develop regulators to minimize skin pigmentation abnormalities. However, only a few of them are used, primarily because of safety concerns and low efficiency. In this study, we aimed to construct a novel nanosphere-gel for sequential delivery of salidroside and paeonol, to investigate the synergistic effects of these drugs in anti-melanogenesis, and to decrease their potential for toxicity in high dosage. Nanospheres were prepared and characterized for their particle size, polydispersity index, zeta potential, and morphological properties. The optimized nanospheres were incorporated in carbomer hydrogel with both paeonol and salidroside entrapped to form a dual drug-releasing nanosphere-gel. With this nanosphere-gel, rapid release of salidroside from the hydrogel followed by sustained release of paeonol from the nanosphere was achieved. Using a classical model of the melanogenesis response to ultraviolet exposure, it was shown that the anti-melanogenesis effects of the dual drug-releasing system, in which the doses of the individual drugs were decreased by half, was obviously enhanced when compared with the effects of the single drug preparations. Mechanistically, the burst release of salidroside from the hydrogel may enable prompt suppression of melanocyte proliferation on exposure to ultraviolet B radiation, while the paeonol released in a sustained manner can provide continuous inhibition of tyrosinase activity in melanocytes. Combined delivery of salidroside and paeonol was demonstrated to be a promising strategy for enhancing the therapeutic efficacy of these agents in anti-melanogenesis and reducing their toxicity, so may have great potential in nanomedicine.

TAT conjugated cationic noble metal nanoparticles for gene delivery to epidermal stem cells.

Most nonviral gene delivery systems are not efficient enough to manipulate the difficult-to-transfect cell types, including non-dividing, primary, neuronal or stem cells, due to a lack of an intrinsic capacity to enter the membrane and nucleus, release its DNA payload, and activate transcription. Noble metal nanoclusters have emerged as a fascinating area of widespread interest in nanomaterials. Herein, we report the synthesis of the TAT peptide conjugated cationic noble metal nanoparticles (metal NPs@PEI-TAT) as highly efficient carriers for gene delivery to stem cells. The metal NPs@PEI-TAT integrate the advantages of metal NPs and peptides: the presence of metal NPs can effectively decrease the cytotoxicity of cationic molecules, making it possible to apply them in biological systems, while the cell penetrating peptides are essential for enhanced cellular and nucleus entry to achieve high transfection efficiency. Our studies provide strong evidence that the metal NPs@PEI-TAT can be engineered as gene delivery agents for stem cells and subsequently enhance their directed differentiation for biomedical application.

Antigen-loaded nanocarriers enhance the migration of stimulated Langerhans cells to draining lymph nodes and induce effective transcutaneous immunization.

This study aims to investigate the efficacy of chitosan nanoparticles (CS-NPs) as a vehicle for transcutaneous antigen delivery in anti-tumor therapy. Ovalbumin (OVA) or gp100 (melanocyte-associated antigen gp100 protein)-loaded CS-sodium tripolyphosphate (TPP)-grafted NPs were prepared by crosslinking low-molecular-weight CS with TPP. Compared with the FITC-OVA solution, the encapsulated fluorescein isothiocyanate (FITC)-OVA-loaded NPs expressed much stronger cellular uptake ability in vitro and higher ability to migrate to lymph nodes in vivo. After transcutaneous administration, OVA-loaded NPs, with imiquimod as an adjuvant, increased the anti-OVA immunoglobulin G titer to levels similar to those induced by the OVA solution. The gp100-loaded NPs promoted the survival of tumor-bearing mice. These results provided evidence of CS-NPs as promising carriers for transcutaneous vaccine delivery, partly contributing to the increased uptake of NPs by skin antigen-presenting cells as well as their enhanced migration to the surrounding lymph nodes. FROM THE CLINICAL EDITOR: In this study the efficacy of chitosan nanoparticle based vehicles for transcutaneous antigen delivery is investigated in anti-tumor therapy. Authors demonstrate that such nanoparticles may be efficient carriers partly due to their increased uptake by antigen-presenting cells in the skin and their enhanced migration to surrounding lymph nodes.

[Research progress of gene recombinant mesenchymal stem cells as tumor targeting delivery vehicles].

The applications of targeting gene delivery systems in tumor therapy have attracted extensive attention of researchers in recent years, as they can selectively deliver the therapeutic gene to tumor sites, improve the success rate of gene therapy and reduce the side effects. Therefore, design and development of novel gene delivery vehicles have been a hot area of current research. Recent studies have shown that mesenchymal stem cells (MSCs) have the ability to migrate towards and engraft into the tumor sites. Therefore, these properties make them a great hope for efficient targeted-delivery vehicles in cancer gene therapy. In this review, we examine the promising of utilization of MSCs as a targeted-delivery vehicle for cancer gene therapy, and summarize various challenges and concerns regarding this therapy.

[Effects of sub-micro emulsion composition on cellular disposition of incorporated lipophilic drug].

OBJECTIVE: To investigate the effects of sub-micro emulsion composition on cellular uptake and disposition of incorporated lipophilic drug. METHODS: Sub-micro emulsions containing 10 % oil, 1.2 % lecithin and 2.25 % glycerol were prepared, and the fluorescent agent coumarin 6 was used as a model drug. The effects of oil types, co-surfactants and cationic lipid on uptake and elimination kinetics of 6-coumarin in HeLa cells were studied. The uptake mechanism of sub-micro emulsions was further investigated. RESULTS: Oil type and Tweens had no influence on the cellular uptake. Modifications of surfactants with Span series increased the cellular influx, among which Span 20 with hydrophilic-lipophilic balance (HLB) value of 8.6 was the best enhancer. The intracellular drug level reached up to (46.09 ± 1.98)ng/µg protein which had significant difference with control group [(38.54 ± 0.34)ng/µg protein]. The positively charged emulsions significantly increased the uptake rate constant and elimination rate constant which were 4 times and 1.5 times of those in anionic groups, respectively. The uptake enhancement was also observed in cationic emulsions, cellular concentrations at plateau were (42.73 ± 0.84)ng/µg protein, which was about 3 times of that in anionic emulsions [(15.71 ± 0.74)ng/µg protein], when extracellular drug concentration kept at 100 ng/ml. Cationic emulsions delivered the payload mainly by direct drug transfer to contacted cells, while the negative ones depended on both drug passive diffusion and clathrin-mediated endocytosis of drug containing oil droplets which accounted for 20% of the intracellular drug. CONCLUSION: Interfacial characteristic of sub-micro emulsions such as co-surfactants HLB as well as zeta potentials can influence lipophilic drug both in cellular uptake and elimination.