Multifunctional hydrogels based on photothermal therapy: A prospective platform for the postoperative management of melanoma.

Preventing the recurrence of melanoma after surgery and accelerating wound healing are among the most challenging aspects of melanoma management. Photothermal therapy has been widely used to treat tumors and bacterial infections and promote wound healing. Owing to its efficacy and specificity, it may be used for postoperative management of tumors. However, its use is limited by the uncontrollable distribution of photosensitizers and the likelihood of damage to the surrounding normal tissue. Hydrogels provide a moist environment with strong biocompatibility and adhesion for wound healing owing to their highly hydrophilic three-dimensional network structure. In addition, these materials serve as excellent drug carriers for tumor treatment and wound healing. It is possible to combine the advantages of both of these agents through different loading modalities to provide a powerful platform for the prevention of tumor recurrence and wound healing. This review summarizes the design strategies, research progress and mechanism of action of hydrogels used in photothermal therapy and discusses their role in preventing tumor recurrence and accelerating wound healing. These findings provide valuable insights into the postoperative management of melanoma and may guide the development of promising multifunctional hydrogels for photothermal therapy.

Lipid-hybrid cell-derived biomimetic functional materials: A state-of-the-art multifunctional weapon against tumors.

Tumors are among the leading causes of death worldwide. Cell-derived biomimetic functional materials have shown great promise in the treatment of tumors. These materials are derived from cell membranes, extracellular vesicles and bacterial outer membrane vesicles and may evade immune recognition, improve drug targeting and activate antitumor immunity. However, their use is limited owing to their low drug-loading capacity and complex preparation methods. Liposomes are artificial bionic membranes that have high drug-loading capacity and can be prepared and modified easily. Although they can overcome the disadvantages of cell-derived biomimetic functional materials, they lack natural active targeting ability. Lipids can be hybridized with cell membranes, extracellular vesicles or bacterial outer membrane vesicles to form lipid-hybrid cell-derived biomimetic functional materials. These materials negate the disadvantages of both liposomes and cell-derived components and represent a promising delivery platform in the treatment of tumors. This review focuses on the design strategies, applications and mechanisms of action of lipid-hybrid cell-derived biomimetic functional materials and summarizes the prospects of their further development and the challenges associated with it.

LncRNA NEAT-2 regulate the function of endothelial progenitor cells in experimental Sepsis model.

BACKGROUND: Sepsis is a life-threatening disease with a limited effectiveness and the potential mechanism remains unclear. LncRNA NEAT-2 is reported to be involved in the regulation of cardiovascular disease. This study aimed to investigate the function of NEAT-2 in sepsis. METHODS: We built sepsis animal model with Male Balb/C mice induced by cecal ligation and puncture (CLP). A total of 54 mice were randomly assigned into eight groups: sham operation group (n = 18), CLP group (n = 18), CLP plus si-control group (n = 3), CLP plus si-NEAT2 group (n = 3), CLP plus mimic control group (n = 3), CLP plus miR-320 group (n = 3), CLP plus normal saline group (n = 3), and normal control group (n = 3). The number of peripheral endothelial progenitor cells (EPCs), the expression level of NEAT-2 and miR-320 were detected during progression of sepsis, as well as the number of peripheral EPCs and level of TNF-α, IL-6, VEGF, ALT, AST and Cr. In addition, the function of EPCs was evaluated after NEAT-2 knockdown and miR-320 overexpression in vitro. RESULTS: The number of circulating EPCs increased significantly in sepsis. NEAT-2 expression was significantly increased in the progress of sepsis, accompanied with miR-320 downregulated. NEAT-2 knockdown and miR-320 overexpression attenuated hepatorenal function and increased cytokines in sepsis. Moreover, NEAT-2 knockdown and miR-320 overexpression decreased the proliferation, migration and angiogenesis of endothelial progenitor cells in vitro. CONCLUSIONS: LncRNA-NEAT2 regulated the number and function of endothelial progenitor cells via miR-320 in sepsis, which may contribute to the development of novel potential clinical therapy for sepsis.

Biomembrane-Based Nanostructure- and Microstructure-Loaded Hydrogels for Promoting Chronic Wound Healing.

Wound healing is a complex and dynamic process, and metabolic disturbances in the microenvironment of chronic wounds and the severe symptoms they cause remain major challenges to be addressed. The inherent properties of hydrogels make them promising wound dressings. In addition, biomembrane-based nanostructures and microstructures (such as liposomes, exosomes, membrane-coated nanostructures, bacteria and algae) have significant advantages in the promotion of wound healing, including special biological activities, flexible drug loading and targeting. Therefore, biomembrane-based nanostructure- and microstructure-loaded hydrogels can compensate for their respective disadvantages and combine the advantages of both to significantly promote chronic wound healing. In this review, we outline the loading strategies, mechanisms of action and applications of different types of biomembrane-based nanostructure- and microstructure-loaded hydrogels in chronic wound healing.

Analysis of risk factors and prevention strategies for functional delayed gastric emptying in 1243 patients with distal gastric cancer.

BACKGROUND: Analysis of the risk factors associated with functional delayed gastric emptying after distal gastric cancer surgery to provide a basis for further reduction of the incidence of this complication. METHODS: Total of 1382 patients with distal gastric cancer from January 2016 to October 2018 were enrolled. Correlation analysis was performed in 53 patients with FDGE by logistic regression. Subgroup risk analysis was performed in 114 patients with preoperative pyloric obstruction. A Pearson Chi-square analysis was used to compare categorical variables between normal distribution groups. Meanwhile, a t test was used to compare continuous variables between groups. Odds ratio (OR) was used for comparison of the two groups, and it was summarized with its 95% confidence interval (CI) and p value using logistic regression. RESULT: In multivariable analysis, age (OR 1.081, 95% CI, 1.047-1.117), BMI (OR 1.233, 95% CI, 1.116-1.363), preoperative pyloric obstruction (OR 3.831, 95% CI, 1.829-8.023), smaller volume of residual stomach (OR 1.838, 95% CI, 1.325-6.080), and anastomosis in greater curvature perpendicular (OR 3.385, 95% CI, 1.632-7.019) and in greater curvature parallel (OR 2.375, 95% CI, 0.963-5.861) were independent risk factors of FDGE. In the preoperative pyloric obstruction group, higher BMI (OR 1.309, 95% CI, 1.086-1.579) and preoperative obstruction time (OR 1.054, 95% CI, 1.003-1.108) were independent risk factors of FDGE and preoperative gastrointestinal decompression (OR 0.231, 95% CI, 0.068-0.785) was independent protective factor of FDGE. CONCLUSION: Adequate gastrointestinal decompression should be performed before the operation to reduce the incidence of postoperative gastroparesis in patients with preoperative pyloric obstruction. We also could improve the surgical methods to reduce the occurrence of FDGE, such as controlling the size of the residual stomach, ensuring blood supply. Especially selecting an appropriate stapler and anastomosis during the anastomosis process, the occurrence of FDGE can be reduced.

Development and validation of a nomogram for preoperative prediction of lymph node metastasis in early gastric cancer.

BACKGROUND: The status of lymph nodes in early gastric cancer is critical to make further clinical treatment decision, but the prediction of lymph node metastasis remains difficult before operation. This study aimed to develop a nomogram that contained preoperative factors to predict lymph node metastasis in early gastric cancer patients. METHODS: This study analyzed the clinicopathologic features of 823 early gastric cancer patients who underwent gastrectomy retrospectively, among which 596 patients were recruited in the training cohort and 227 patients in the independent validation cohort. Significant risk factors in univariate analysis were further identified to be independent variables in multivariable logistic regression analysis, which were then incorporated in and presented with a nomogram. And internal and external validation curves were plotted to evaluate the discrimination of the nomogram. RESULTS: Totally, six independent predictors, including the tumor size, macroscopic features, histology differentiation, P53, carbohydrate antigen 19-9, and computed tomography-reported lymph node status, were enrolled in the nomogram. Both the internal validation in the training cohort and the external validation in the validation cohort showed the nomogram had good discriminations, with a C-index of 0.82 (95%CI, 0.78 to 0.86) and 0.77 (95%CI, 0.60 to 0.94) respectively. CONCLUSIONS: Our study developed a new nomogram which contained the most common and significant preoperative risk factors for lymph node metastasis in patients with early gastric cancer. The nomogram can identify early gastric cancer patients with the high probability of lymph node metastasis and help clinicians make more appropriate decisions in clinical practice.

Emodin enhances osteogenesis and inhibits adipogenesis.

BACKGROUND: It has been suggested that the formation of osteoblasts in bone marrow is closely associated with adipogenesis, and the balance between osteogenesis and adipogenesis differentiation of MSCs (mesenchymal stem cells) is disrupted in osteoporosis. In order to improve the treatment of osteoporosis, available agents with roles of regulating the balance is highly desirable. Emodin is a natural anthraquinone derivative extracted from Chinese herbs, which have been used to treat bone diseases for thousands of years. However, the underlying molecular mechanisms of emodin in modulating osteogenesis and adipogenesis remain poorly understood. METHODS: The molecular mechanisms of emodin on the processes of osteogenesis and adipogenesis in ovariectomized mouse and BMSCs (bone marrow mesenchymal stem cells) have been studied. We have analyzed the effects of emodin in vivo and in vitro. Female ICR mice were assigned to three groups: sham group, ovariectomy group, emodin group. Efficacy was evaluated by H&E, immunohistochemical assay and Micro-CT. In vitro, we analyze the effect of emodin--at concentrations between 0.1 µM and 10 µM--on the processes of inducing osteogenesis and inhibiting adipogenesis in BMSCs by ALP, Oil red O staining, real time RT-PCR and western blot. RESULTS: As our experiment shows that emodin could increase the number of osteoblast, BMD (bone mineral density), BV/TV (trabecular bone volume fraction), Tb.N (trabecular number) and Conn.D (connectivity density) of OVX (ovariectomized) mice and decrease the bone marrow fat tissue and adipocytes. The genes and proteins expression of osteogenesis markers, such as Runx2, osterix, collagen type I, osteocalcin, or ALP were up-regulated. While, the genes and proteins involved in adipogenesis, PPARγ, C/EBPα and ap2 were down-regulated. CONCLUSION: It proves that emodin inhibits adipocyte differentiation and enhances osteoblast differentiation from BMSCs.

Influence of ERCC1 and ERCC4 polymorphisms on response to prognosis in gastric cancer treated with FOLFOX-based chemotherapy.

Polymorphisms in the excision repair cross-complimentary group 1 (ERCC1)-excision repair cross-complimentary group 4 (ERCC4) genes have been implicated in the prognosis of various cancers. We conducted a cohort study to investigate the role of ERCC1-ERCC4 gene polymorphisms on the response to chemotherapy and the role of these two gene polymorphisms on the clinical outcomes of gastric cancer. Four hundred forty-seven patients with newly diagnosed and histopathologically confirmed primary gastric cancer were collected in our study and were followed up until March 2012. ERCC1 (rs11615, rs3212986C>A, and rs2298881) and ERCC4 (rs226466C>G, rs2276465, and rs6498486) were selected and genotyped. The overall chemotherapy response rate for treatment was 68 %. Carriers of the rs11615 TT and T allele and ERCC1 rs2298881 CC and C allele had a marginally significantly higher response rate to the chemotherapy. In the Cox proportional hazard model, the hazard ratios (HRs) for overall survival (OS) in patients carrying ERCC1 rs11615 TT genotype and T allele were 0.53 (0.29-0.95) and 0.63 (0.42-0.94), respectively. Similarly, we found a significant decreased risk of death from gastric cancer among patients carrying ERCC1 rs2298881 CC genotype and C allele when compared with CC genotype, and HRs (95% confidence interval (CI)) of OS were 0.50 (0.24-0.98) and 0.62 (0.40-0.96), respectively. Moreover, individuals carrying ERCC1 rs11615 T allele and rs2298881 C allele could decrease a 0.62-fold risk of death from gastric cancer. This study reported a carriage of ERCC1 rs11615, and rs2298881 polymorphism can be used as a predictor of response to folinic acid/5-fluorouracil (5-FU)/oxaliplatin (FOLFOX)-based chemotherapy in gastric cancer patients.

[Isolation, culture and identification of rabbit bone marrow-derived vascular endothelial progenitor cells].

The aim of study was to set up a suitable method of isolation, culture and identification of endothelial progenitor cells (EPC) derived from rabbit bone marrow. Density gradient centrifugation was used to isolate mononuclear cells from bone marrow, the isolated mononuclear cells were cultured with specific culture medium for EPCs. EPCs were identified by cellular morphologic observation, immunohistochemistry testing, flow cytometry and the function test of taking up Dil-ac-LDL and FITC-UEA-1. The results indicated that the newly isolated bone marrow-derived mononuclear cells exhibited a round appearance, following culture for 48 hours, adherent cells grew in colony cluster, presenting with round or irregular appearance, and nuclear division was obvious. On day 7, flaky cell colonies mutually connected together, presenting with spindle-shaped cells. Immunohistochemistry testing in the EPCs showed CD133(+), CD34(+), VIII factor(++), KDR(++); flow cytometry testing showed that the positive rate of CD133 was (18.23+/-7.12)%, the positive rate of CD34 was 47.71+/-14.85%, the positive rate of CD31 was (71.61+/-13.51)%, the positive rate of KDR was (87.24+/-11.40)%. And more than 80% EPC could take up both Dil-acLDL and FITC-UEA-1. It is concluded that the mononuclear cells isolated from bone marrow by density gradient centrifugation can differentiate into EPCs under special culture situation.

The change and effect of endothelial progenitor cells in pig with multiple organ dysfunction syndromes.

INTRODUCTION: The dysfunction and decrease of endothelial progenitor cells (EPCs) may play a very important role in the initiation of organ dysfunction caused by trauma or severe sepsis. We aim to measure the number and function of EPCs in the progression of multiple organ dysfunction syndromes (MODS) caused by severe sepsis, which may help to understand the pathogenesis of MODS by the changing of EPCs. METHODS: A total of 40 pigs were randomly divided into two groups, which were subjected to hemorrhagic shock, resuscitation and endotoxemia (experimental group, n = 20) or acted as a control (control group, n = 20). The number and function of EPCs including adhesive, migratory and angiogenesis capacities were analyzed at different times in both groups. RESULTS: All the animals in the experimental group developed MODS (100%) and 17 of 20 animals (85%) died due to MODS; the incidence of MODS and death of the animals in the control group were 0% (P < 0.01). The number, migratory and adhesive capacities of EPCs decreased sharply in the animals of the experimental group corresponding to the increasing severities of MODS, but the angiogenesis function increased gradually until death. The decrease in function of EPCs preceded the decrease in number of EPCs. The decrease in number and function of EPCs occurred prior to the occurrence of MODS. CONCLUSIONS: For the first time, it was observed that the number and function of EPCs decreased sharply in the progression of MODS and that it was prior to the occurrence of MODS. The decrease in number and function of EPCs may be one of the main pathogenic factors of MODS.