Atypical hemolytic uremic syndrome with C3 mutation: A case report and literature review.

INTRODUCTION: Atypical hemolytic uremic syndrome (aHUS) is characterized by hemolytic anemia, thrombocytopenia, and acute kidney injury. Uncontrolled activation of the complement system induced by single or combined complement gene mutations is one of the mechanisms leading to the pathogenesis of aHUS. CASE PRESENTATION: We report a case of a 26-year-old female with a C3 heterozygous gene mutation (p.Asn153Asn). The patient was found to have low complement H factor (CFH) but normal levels of anti-CFH autoantibody. She was treated primarily with plasma exchange and plasma infusion. The patient did not relapse during a 1-year follow-up. CONCLUSION: This is the first case of a novel C3 mutation (p.Asn153Asn) in a patient with aHUS. Further studies are needed to confirm the association between this mutation and the CFH level.

Nanoparticle-Embedded Electrospun Fiber-Covered Stent to Assist Intraluminal Photodynamic Treatment of Oesophageal Cancer.

Drug-eluting stents (DESs) are promising candidates for treating human oesophageal cancer. However, the use of DESs to assist photodynamic therapy (PDT) of orthotopic oesophageal tumors is not yet demonstrated to the best of current knowledge. Herein, through an electrospinning technology it is shown that oxygen-producing manganese dioxide nanoparticles are embedded into elelctrospun fibers, which are subsequently covered onto stents. Upon implantation, the nanoparticles are gradually released from the fibers and then diffuse into the nearby tumor tissue. Then, the hypoxic microenvironment can be effectively alleviated by reaction of MnO2 with the endogenous H2 O2 within the tumor. After demonstrating the excellent PDT efficacy of the stents in a conventional subcutaneous mouse tumor model, such stents are further used for PDT treatment in a rabbit orthotopic oesophageal cancer model by inserting an optical fiber into the tumor site. Greatly prolonged survival of rabbits is observed after such intraluminal PDT treatment. Taken together, this work shows that the fiber-covered stent as a nanoparticle delivery platform can enable effective PDT as a noninvasive treatment method for patients with advanced-stage oesophageal cancer.

Combined with interventional therapy, immunotherapy can create a new outlook for tumor treatment.

Recent progress in immunotherapy provides hope of a complete cure to cancer patients. However, recent studies have reported that only a limited number of cancer patients with a specific immune status, known as "cold tumor", can benefit from a single immune agent. Although the combination of immune agents with different mechanisms can partially increase the low response rate and improve efficacy, it can also result in more side effects. Therefore, discovering therapies that can improve tumors' response rate to immunotherapy without increasing toxicity for patients is urgently needed. Tumor interventional therapy is promising. It mainly includes transcatheter arterial chemoembolization, ablation, radioactive particle internal irradiation, and photodynamic interventional therapy based on a luminal stent. Interventional therapy can directly kill tumor cells by targeted drug delivery in situ, thus reducing drug dosage and systemic toxicity like cytokine release syndrome. More importantly, interventional therapy can regulate the immune system through numerous mechanisms, making it a suitable choice for immunotherapy to combine with. In this review, we provide a brief description of immunotherapies (and their side effects) on tumors of different immune types and preliminarily elaborate on interventional therapy mechanisms to improve immune efficacy. We also discuss the progress and challenges of the combination of interventional therapy and immunotherapy.

Recombination Monophosphoryl Lipid A-Derived Vacosome for the Development of Preventive Cancer Vaccines.

Recently, there has been an increasing interest for utilizing the host immune system to fight against cancer. Moreover, cancer vaccines, which can stimulate the host immune system to respond to cancer in the long term, are being investigated as a promising approach to induce tumor-specific immunity. In this work, we prepared an effective cancer vaccine (denoted as "vacosome") by reconstructing the cancer cell membrane, monophosphoryl lipid A as a toll-like receptor 4 agonist, and egg phosphatidylcholine. The vacosome triggered and enhanced bone marrow dendritic cell maturation as well as stimulated the antitumor response against breast cancer 4T1 cells in vitro. Furthermore, an immune memory was established in BALB/c mice after three-time preimmunization with the vacosome. After that, the immunized mice showed inhibited tumor growth and prolonged survival period (longer than 50 days). Overall, our results demonstrate that the vacosome can be a potential candidate for clinical translation as a cancer vaccine.

An electrospun fiber-covered stent with programmable dual drug release for endothelialization acceleration and lumen stenosis prevention.

Aneurysmal subarachnoid hemorrhage (SAH) causes high rates of mortality and morbidity. A covered stent is an effective endovascular treatment for complicated aneurysms intractable to endovascular coiling and surgical clipping. However, in-stent restenosis and delayed endothelialization are the main challenges contributing to its safety. In this study, we designed a biofunctional stent covered with dual drug-loaded electrospun fibers to achieve programmed vascular endothelial growth factor (VEGF) and paclitaxel (PTX) release for the early promotion of stent endothelialization and long-term inhibition of stenosis caused by smooth muscle hyperplasia. By encapsulating PTX-loaded mesoporous silica nanoparticles (MSNs) within electrospun polylactic acid (PLA) fibers, the release period of PTX was effectively extended. Furthermore, VEGF was conjugated onto the surface of the membrane by reacting with polydopamine (PDA) for quick release. The in vitro drug release profile revealed the sustained release of PTX, which persisted for 63 days without early burst release, while up to 87.05% of VEGF was rapidly released within 3 days. After 6 days of incubation, cell experiments demonstrated that the dual drug-loaded scaffold effectively prompted endothelial cell proliferation (488% vs. 386% in the control group, P = 0.001) and inhibited the proliferation of smooth muscle cells (SMCs) using the 21-day extracts (155% vs. 303% in the control group, P = 0.039). Animal studies showed that compared to bare stents, the drug-loaded covered stents improved the immediate- and mid-term complete aneurysm occlusion rates (P < 0.05). The drug-loaded covered stents also showed earlier endothelialization promotion and better lumen restenosis than normal covered stents (0% vs. 25%, P = 0.29) for 12 weeks. Overall, a programmed dual drug-loaded scaffold that effectively occluded the aneurysm sac was developed in this study, and the discrete release of VEGF and PTX promoted endothelialization and prevented in-stent stenosis. This study provided a new method to improve the biosafety of implanted covered stents for the treatment of intracranial aneurysms. STATEMENT OF SIGNIFICANCE: Aneurysmal subarachnoid hemorrhage (SAH) is one of the most common hemorrhage stroke resulted in a nearly 40% mortality and 33% morbidity due to sudden rupture of an intracranial aneurysm. Endovascular coil embolism is a popular treatment for aneurysm but this technique run high risk of bleeding, mass effect, low complete occlusion rate and higher recanalization rate due to its operation conducted within aneurysm sac. A bio-functional membrane knitted by dual-drug loaded electrospun fibers covered on a stent was designed to realize programed vascular endothelial growth factor and paclitaxel release for the early promotion of vascular endothelium and long-term inhibition of stenosis caused by smooth muscle hyperplasia. This study provides new method to improve the biosafety of covered stent insertion for the treatment of intracranial aneurysms.

Charge-switchable nanocapsules with multistage pH-responsive behaviours for enhanced tumour-targeted chemo/photodynamic therapy guided by NIR/MR imaging.

Multifunctional nanoplatforms have been developed into advanced drug delivery systems for cancer therapy. In this study, we report a charge-switchable nanocapsule with multistage pH-responsive behaviors. First, DOX-encapsulated and oleylamine-embedded hollow structures with a diameter of 132 ± 21 nm are prepared via the double emulsion method. Subsequently, the hollow structures are encompassed by Gd-DTPA-, chlorin e6 (Ce6)-, and folate (FA)-modified BSA to form tumour-targeted, dual NIR/MR imaging-guided and chemo-photodynamic therapeutic nanoplatforms. Importantly, the nanocapsule can intelligently switch its surface charge to positive under mildly acidic conditions (pH 6.5) with no release of Ce6 and DOX, which is confirmed by ξ-potential and cumulative release measurements. Moreover, confocal imaging pictures demonstrate that acid-sensitive DOX sealed in nanocapsules is progressively released into the nuclei of MGC-803 cells. These advantages as well as FA-targeting facilitate effective endocytosis and synergistic therapeutic efficacy. Selective tumour accumulation and long tumour retention time are further indicated by NIR/MR in vivo imaging. In addition, excellent therapeutic efficacy combined with chemotherapy (DOX) and photodynamic therapy (PDT) is observed with the tumour eventually ablating at the 15th day. All results demonstrate that the as-prepared nanocapsules hold great potential for clinical cancer theranostics.

Active components, derived from Kai-xin-san, a herbal formula, increase the expressions of neurotrophic factor NGF and BDNF on mouse astrocyte primary cultures via cAMP-dependent signaling pathway.

ETHNOPHARMACOLOGICAL RELEVANCE: Kai-Xin-San (KXS), an ancient formula composed of Ginseng Radix et Rhizoma, Polygalae Radix, Acori Tatarinowii Rhizoma and Poria, was frequently applied for Alzheimer's disease and major depression disorders for thousands of years. However, its active components and molecular mechanism have not clearly been investigated. AIM OF THE STUDY: We aimed to reveal the active components of KXS on regulating neurotrophic factor NGF and BDNF expressions and its mechanisms on mouse astrocyte primary cultures. MATERIALS AND METHODS: Extracts of KXS had been prepared by water reflux and chemical standardization was carried out by HPLC-MS/MS. Various ethanol elution components were prepared by eluting ethanol on macro pore resin column and compound identification was carried out by high-resolution mass spectrometry. KXS extract, elution components and identified chemicals were applied on mouse astrocytes and expressions of NGF and BDNF and related metabolic enzymes were analyzed by qPCR and western blotting analysis. RESULTS: One compatible ratio of KXS named D-652 exerted the best effect on stimulation of NGF and BDNF expressions on mouse astrocytes. 70% ethanol elution fraction of D-652 exerted the highest increase tendency on expressions of NGF and BDNF by activating cAMP-dependent signaling pathway as well as stimulating enzymes accounting for neurotrophic factor synthesis. Combined with compound identification by high-resolution mass spectrometry, ginsenoside Rg1 and Rb1 might be the active compounds of this fraction on increasing NGF and BDNF expressions. CONCLUSIONS: The active compounds of KXS on increasing NGF and BDNF expressions might be the ginsenosides via activating cAMP-dependent signaling pathway as well as stimulating enzymes accounting for neurotrophic factor synthesis, which partly reveal the target of this formulae supported the clinically usage of this decoction.

Advances in biomaterials for preventing tissue adhesion.

Adhesion is one of the most common postsurgical complications, occurring simultaneously as the damaged tissue heals. Accompanied by symptoms such as inflammation, pain and even dyskinesia in particular circumstances, tissue adhesion has substantially compromised the quality of life of patients. Instead of passive treatment, which involves high cost and prolonged hospital stay, active intervention to prevent the adhesion from happening has been accepted as the optimized strategy against this complication. Herein, this paper will cover not only the mechanism of adhesion forming, but also the biomaterials and medicines used in its prevention. Apart from acting as a direct barrier, biomaterials also show promising anti-adhesive bioactivity though their intrinsic physical and chemical are still not completely unveiled. Considering the diversity of human tissue organization, it is imperative that various biomaterials in combination with specific medicine could be tuned to fit the microenvironment of targeted tissues. With the illustration of different adhesion mechanism and solutions, we hope this review can become a beacon and further inspires the development of anti-adhesion biomedicines.