LncRNA TTN-AS1 acts as a tumor promoter in gallbladder carcinoma by regulating miR-107/HMGA1 axis.

BACKGROUND: The incidence of gallbladder carcinoma (GBM) in China has increased in recent years. Here, the functional mechanism of lncRNA TTN-AS1 in GBC was preliminary elucidated. METHODS: The expression levels of lncRNA TTN-AS1, miR-107, and HMGA1 in tissues and cell lines were assessed by RT-qPCR. Cell proliferation was measured by MTT assays. Cell invasion and migration abilities were evaluated by Transwell assays. The relationship between miR-107 and lncRNA TTN-AS1 or HMGA1 was confirmed by luciferase reporter assay. RESULTS: Upregulation of lncRNA TTN-AS1 and downregulation of miR-107 were detected in GBC. Furthermore, the expressions between TTN-AS1 and miR-107 were mutually inhibited in GBC. Functionally, lncRNA TTN-AS1 promoted cell viability and motility in GBC by sponging miR-107. In addition, miR-107 directly targets HMGA1. And HMGA1 can be positively regulated by lncRNA TTN-AS1 in GBC. Furthermore, HMGA1 promoted GBC progression by interacting with lncRNA TTN-AS1/miR-107 axis. CONCLUSION: LncRNA TTN-AS1 acted as a tumor promoter in GBC by sponging miR-107 and upregulating HMGA1.

Lyophilizable Stem Cell-Hybrid Liposome with Long-Term Stability and High Targeting Capacity.

The hybridization of liposome with stem cell membranes is an emerging technology to prepare the nanovehicle with the capacity of disease-responsive targeting. However, the long-term storage of this hybrid liposome has received limited attention in the literature, which is essential for its potential applicability in the clinic. Therefore, the preservation of long-term activity of stem cell-hybrid liposome using freeze-drying is investigated in the present study. Mesenchymal stem cell-hybrid liposome is synthesized and its feasibility for freeze-drying under different conditions is examined. Results reveal that pre-freezing the hybrid liposome at -20 °C in Tris buffer solution (pH 7.4) containing 10% trehalose can well preserve the liposomal structure for at least three months. Notably, major membrane proteins on the hybrid liposome are protected in this formulation and CXCR4-associated targeting capacity is maintained both in vitro and in vivo. Consequently, the hybrid liposome stored for three months demonstrates a comparable tumor inhibition as the fresh-prepared one. The present study provides the first insights into the long-term storage of stem cell hybrid liposome using lyophilization, which may make an important step forward in enhancing the long-term stability of these promising biomimetic nanovehicle and ease the logistics and the freeze-storage in the potential clinical applications.

Precisely targeted drug delivery by mesenchymal stem cells-based biomimetic liposomes to cerebral ischemia-reperfusion injured hemisphere.

The precise and targeted delivery of therapeutic agents to the lesion sites remains a major challenge in treating brain diseases represented by ischemic stroke. Herein, we modified liposomes with mesenchymal stem cells (MSC) membrane to construct biomimetic liposomes, termed MSCsome. MSCsome (115.99 ± 4.03 nm) exhibited concentrated accumulation in the cerebral infarcted hemisphere of mice with cerebral ischemia-reperfusion injury, while showing uniform distribution in the two cerebral hemispheres of normal mice. Moreover, MSCsome exhibited high colocalization with damaged nerve cells in the infarcted hemisphere, highlighting its advantageous precise targeting capabilities over liposomes at both the tissue and cellular levels. Leveraging its superior targeting properties, MSCsome effectively delivered Dl-3-n-butylphthalide (NBP) to the injured hemisphere, making a single-dose (15 mg/kg) intravenous injection of NBP-encapsulated MSCsome facilitate the recovery of motor functions in model mice by improving the damaged microenvironment and suppressing neuroinflammation. This study underscores that the modification of the MSC membrane notably enhances the capacity of liposomes for precisely targeting the injured hemisphere, which is particularly crucial in treating cerebral ischemia-reperfusion injury.

Inorganic nanoparticle-integrated mesenchymal stem cells: A potential biological agent for multifaceted applications.

Mesenchymal stem cell (MSC)-based therapies are flourishing. MSCs could be used as potential therapeutic agents for regenerative medicine due to their own repair function. Meanwhile, the natural predisposition toward inflammation or injury sites makes them promising carriers for targeted drug delivery. Inorganic nanoparticles (INPs) are greatly favored for their unique properties and potential applications in biomedical fields. Current research has integrated INPs with MSCs to enhance their regenerative or antitumor functions. This model also allows the in vivo fate tracking of MSCs in multiple imaging modalities, as many INPs are also excellent contrast agents. Thus, INP-integrated MSCs would be a multifunctional biologic agent with great potential. In this review, the current roles performed by the integration of INPs with MSCs, including (i) enhancing their repair and regeneration capacity via the improvement of migration, survival, paracrine, or differentiation properties, (ii) empowering tumor-killing ability through agent loaded or hyperthermia, and (iii) conferring traceability are summarized. An introduction of INP-integrated MSCs for simultaneous treatment and tracking is also included. The promising applications of INP-integrated MSCs in future treatments are emphasized and the challenges to their clinical translation are discussed.

New idea to promote the clinical applications of stem cells or their extracellular vesicles in central nervous system disorders: Combining with intranasal delivery.

The clinical translation of stem cells and their extracellular vesicles (EVs)-based therapy for central nervous system (CNS) diseases is booming. Nevertheless, the insufficient CNS delivery and retention together with the invasiveness of current administration routes prevent stem cells or EVs from fully exerting their clinical therapeutic potential. Intranasal (IN) delivery is a possible strategy to solve problems as IN route could circumvent the brain‒blood barrier non-invasively and fit repeated dosage regimens. Herein, we gave an overview of studies and clinical trials involved with IN route and discussed the possibility of employing IN delivery to solve problems in stem cells or EVs-based therapy. We reviewed relevant researches that combining stem cells or EVs-based therapy with IN administration and analyzed benefits brought by IN route. Finally, we proposed possible suggestions to facilitate the development of IN delivery of stem cells or EVs.

Peptide nano-blanket impedes fibroblasts activation and subsequent formation of pre-metastatic niche.

There is evidence to suggest that the primary tumor induces the formation of a pre-metastatic niche in distal organs by stimulating the production of pro-metastatic factors. Given the fundamental role of the pre-metastatic niche in the development of metastases, interruption of its formation would be a promising strategy to take early action against tumor metastasis. Here we report an enzyme-activated assembled peptide FR17 that can serve as a "flame-retarding blanket" in the pre-metastatic niche specifically to extinguish the "fire" of tumor-supportive microenvironment adaption. We show that the in-situ assembled peptide nano-blanket inhibits fibroblasts activation, suppressing the remodeling of the metastasis-supportive host stromal tissue, and reversing vascular destabilization and angiogenesis. Furthermore, we demonstrate that the nano-blanket prevents the recruitment of myeloid cells to the pre-metastatic niche, regulating the immune-suppressive microenvironment. We show that FR17 administration effectively inhibits the formation of the pulmonary pre-metastatic niche and postoperative metastasis, offering a therapeutic strategy against pre-metastatic niche formation.

Active stealth and self-positioning biomimetic vehicles achieved effective antitumor therapy.

Mesenchymal stem cells (MSCs) are recognized as promising drug delivery vehicles. However, the limitation of drug loading capacity and safety considerations are two obstacles to the further application of MSCs. Here, we report MSC membrane-coated mesoporous silica nanoparticles (MSN@M) that maintain the active stealth and self-positioning drug delivery abilities of MSCs and resolve issues related to MSCs-mediated drug delivery. MSN@M was established through uniformly integrating MSC membrane onto a mesoporous silica nanoparticle (MSN) core by sonication. Reduced clearance of phagocytes mediated by CD47 marker on MSC membrane was observed in vitro, which explained the only ~ 25% clearance rate of MSN@M compared with MSN in vivo within 24 h. MSN@M also showed stronger tumor targeting and penetration ability compared with MSN in HepG2 tumor bearing mice. Simultaneously, MSN@M exhibited strong capacity for drug loading and sustained drug release ability of MSN when loaded with doxorubicin (DOX), the drug loading of MSN@M increased ~ 5 folds compared with MSC membrane. In HepG2 xenograft mice, DOX-loaded MSN@M effectively inhibited the growth of tumors and decreased the side effects of treatment by decreasing the exposure of other tissues to DOX. Consequently, our MSN@M may serve as alternative vehicles for MSCs and provide more options for antitumor treatment.

Manipulation of the magnetoresistance effect in a double-helix DNA.

Magnetoresistance (R m) of a double-stranded (G:C) N DNA sandwiched between ferromagnetic electrodes has been studied using the transfer matrix method of the tight-binding model. A R m magnitude up to 72.5% for DNA in its natural structure is observed when the spin-orbit coupling with the helix spring geometry and a possible dephasing effect are taken into account. It can be greatly manipulated by stress or torque applied to the DNA with respect to its axis. In addition, the external voltage bias can also be used to efficiently control R m. The dependence of R m on the DNA length in a decaying oscillation form is observed.

[Reverse second dorsal metatarsal artery island flap for repairing the soft tissue defect at toes].

OBJECTIVE: To report the application of reverse second dorsal metatarsal artery island flap for From May 2005 to September 2008, 5 cases with soft tissue repairing the soft tissue defect at toes. METHODS: defects at toes were treated with reverse second dorsal metatarsal artery island flaps. The flaps size ranged from 2 cm x 3 cm to 5 cm x 6 cm. RESULTS: All the 5 flaps survived completely. The patients could walk 1-2 months after operation. The patients were followed up for 5-7 months with good appearance, texture and sensation of toes. CONCLUSION: The reverse second dorsal metatarsal artery island flap has a reliable blood supply and good tissue texture. It is a practical method for repairing the soft tissue defect at toes.

[Repair of the soft tissue defect of the fifth finger with a reversed ulnar fasciocutaneous flap from the fifth metacarpal side].

OBJECTIVE: To introduce a method by reversed ulnar fasciocutaneous flap incised form the ulnar side of the fifth metacarpal area for repairing the soft tissue defect of the fifth finger. METHODS: From May 2001 to September 2001, ten patients with the soft tissue defects of the thenar side, dorsal side or ulnar side of the fifth finger were treated with the reversed ulnar fasciocutaneous flap incised from the fifth metacarpal area. The axial line of the flap was the line from ulnar side of the head of the fifth metacarpal bone to the pisiform level. The revolving point of the flap pedicle was 0.5-1 cm near the proximal end of the metacarpal-phalangeal joint.The area of the flap was form 5.0 cm x 3.5 cm to 1.5 cm x 1.0 cm. RESULTS: All flaps of the ten cases were alive. 5-7 months followed-up show that, after operation, the flap present sensation in 6-12 mm, with soft texture and good appearances. CONCLUSIONS: The advantages of this operative method were as follows: the reversed ulnar fasciocutaneous flap of the fifth metacarpal area have reliable blood supply, it was easily dissected and with good texture. So far this kind of flap is a good choice in repairing the soft tissue of the fifth finger.