Targeted drug delivery of engineered mesenchymal stem/stromal-cell-derived exosomes in cardiovascular disease: recent trends and future perspectives.

In recent years, stem cells and their secretomes, notably exosomes, have received considerable attention in biomedical applications. Exosomes are cellular secretomes used for intercellular communication. They perform the function of intercellular messengers by facilitating the transport of proteins, lipids, nucleic acids, and therapeutic substances. Their biocompatibility, minimal immunogenicity, targetability, stability, and engineerable characteristics have additionally led to their application as drug delivery vehicles. The therapeutic efficacy of exosomes can be improved through surface modification employing functional molecules, including aptamers, antibodies, and peptides. Given their potential as targeted delivery vehicles to enhance the efficiency of treatment while minimizing adverse effects, exosomes exhibit considerable promise. Stem cells are considered advantageous sources of exosomes due to their distinctive characteristics, including regenerative and self-renewal capabilities, which make them well-suited for transplantation into injured tissues, hence promoting tissue regeneration. However, there are notable obstacles that need to be addressed, including immune rejection and ethical problems. Exosomes produced from stem cells have been thoroughly studied as a cell-free strategy that avoids many of the difficulties involved with cell-based therapy for tissue regeneration and cancer treatment. This review provides an in-depth summary and analysis of the existing knowledge regarding exosomes, including their engineering and cardiovascular disease (CVD) treatment applications.

Oncolytic Virotherapy in Peritoneal Metastasis Gastric Cancer: The Challenges and Achievements.

Gastric cancer (GC) is the fourth most common cancer and the second leading cause of cancer death globally. Although the mortality rate in some parts of the world, such as East Asia, is still high, new treatments and lifestyle changes have effectively reduced deaths from this type of cancer. One of the main challenges of this type of cancer is its late diagnosis and poor prognosis. GC patients are usually diagnosed in the advanced stages of the disease, which is often associated with peritoneal metastasis (PM) and significantly reduces survival. This type of metastasis in patients with GC poses a serious challenge due to limitations in common therapies such as surgery and tumor resection, as well as failure to respond to systemic chemotherapy. To solve this problem, researchers have used virotherapy such as reovirus-based anticancer therapy in patients with GC along with PM who are resistant to current chemotherapies because this therapeutic approach is able to overcome immune suppression by activating dendritic cells (DCs) and eventually lead to the intrinsic activity of antitumor effector T cells. This review summarizes the immunopathogenesis of peritoneal metastasis of gastric cancer (PMGC) and the details for using virotherapy as an effective anticancer treatment approach, as well as its challenges and opportunities.

Design and Development of Hybrid Hydrogels for Biomedical Applications: Recent Trends in Anticancer Drug Delivery and Tissue Engineering.

The applications of hydrogels in biomedical field has been since multiple decades. Discoveries in biology and chemistry render this platform endowed with much engineering potentials and growing continuously. Novel approaches in constructing these materials have led to the production of complex hybrid hydrogels systems that can incorporate both natural and synthetic polymers and other functional moieties for mediated cell response, tunable release kinetic profiles, thus they are used and research for diverse biomedical applications. Recent advancement in this field has established promising techniques for the development of biorelevant materials for construction of hybrid hydrogels with potential applications in the delivery of cancer therapeutics, drug discovery, and re-generative medicines. In this review, recent trends in advanced hybrid hydrogels systems incorporating nano/microstructures, their synthesis, and their potential applications in tissue engineering and anticancer drug delivery has been discussed. Examples of some new approaches including click reactions implementation, 3D printing, and photopatterning for the development of these materials has been briefly discussed. In addition, the application of biomolecules and motifs for desired outcomes, and tailoring of their transport and kinetic behavior for achieving desired outcomes in hybrid nanogels has also been reviewed.

Delivery systems for enhancing oncolytic adenoviruses efficacy.

Oncolytic adenovirus (OAds) has long been considered a promising biotherapeutic agent against various types of cancer owing to selectively replicate in and lyse cancer cells, while remaining dormant in healthy cells. In the last years, multiple (pre)clinical studies using genetic engineering technologies enhanced OAds anti-tumor effects in a broad range of cancers. However, poor targeting delivery, tropism toward healthy tissues, low-level expression of Ad receptors on tumor cells, and pre-existing neutralizing antibodies are major hurdles for systemic administration of OAds. Different vehicles have been developed for addressing these obstacles, such as stem cells, nanoparticles (NPs) and shielding polymers, extracellular vesicles (EVs), hydrogels, and microparticles (MPs). These carriers can enhance the therapeutic efficacy of OVs through enhancing transfection, circulatory longevity, cellular interactions, specific targeting, and immune responses against cancer. In this paper, we reviewed adenovirus structure and biology, different types of OAds, and the efficacy of different carriers in systemic administration of OAds.

The limiting factors of oncolytic virus immunotherapy and the approaches to overcome them.

Oncolytic virus (OV) immunotherapy is characterized by viruses which specifically target cancer cells and cause their cytolysis. They provide a unique and promising new tool for the eradication of cancer as they interact with and affect the tumor microenvironment (TME), vasculature, and immune system. Advancements of genetic engineering have allowed for these viruses to be armed in such a way to have enhanced targeting, strong immunomodulation properties, and an ability to modify the TME. However, there are still major limitations in their use, mostly due to difficulties in delivering the viral particles to the tumors and in ensuring that the immunomodulatory properties are able to stimulate the host immune response to mount a complete response. Using novel delivery systems and using OVs as a complementary therapy in a combinatorial treatment have shown some significant successes. In this review, we discuss the major issues and difficulties in using OVs as anti-tumor agents and some of the strategies put in place so far to overcome these limitations. KEY POINTS: • Oncolytic viruses (OVs) infect cancer cells and cause their cytolysis. • The major limitations in using OVs as anti-tumor therapy were discussed. • The potential strategies to overcome these limitations were summarized.

Recent advances in targeting cancer stem cells using oncolytic viruses.

Oncolytic virotherapy is a promising antitumor strategy which utilizes the lytic nature of viral replication to kill cancer cells. Oncolytic viruses (OVs) can induce cancer cell death and trigger immune responses to metastatic cancer in vivo. Reverse genetic systems have aided the insertion of anticancer genes into various OVs to augment their oncolytic capacity. Furthermore, OVs target and destroy the population of tumor-initiating cancer stem cells. These cancer stem cells are associated with metastasis and development of resistance to conventional anticancer approaches. Targeting cancer stem cells is essential since killing only differentiated tumor cells may lead to enrichment of cancer stem cells and thus indicate a poor prognosis. In this review, we summarize the oncolytic activity of various classes of OVs towards different types of cancer stem cells and also discuss the synergistic activity achieved by the combination of OVs with traditional therapies on chemo- and radiotherapy-resistant cancer stem cells.

Effects of batroxobin treatment on the survival of random skin flaps in rats.

OBJECTIVE: Batroxobin is a medicinal preparation extracted from the venom of the Fer-de-Lance snake, and is used to lower blood viscosity, promote blood fibrinogen decomposition, and inhibit thrombosis. This research is to investigate whether batroxobin can improve the survival of random skin flaps in a rat model. MATERIALS AND METHODS: Dorsal McFarlane flaps were harvested from 36 rats divided into two groups. Experimental group: Batroxobin was administered via the tail vein once daily. CONTROL GROUP: The same amount of normal saline was injected instead. On day 2, superoxide dismutase (SOD) and malondialdehyde (MDA) levels were measured. On day 7, tissue slices were stained with haematoxylin and eosin. Expression of vascular endothelial growth factor (VEGF) was immunohistochemically evaluated. Microcirculatory flow was measured by laser Doppler flowmetry. Flap angiography, using the lead oxide-gelatin injection technique, was performed with the aid of a soft X-ray machine. RESULTS: The batroxobin group exhibited a greater mean flap survival area, a better microcirculatory flow, and higher-level expression of SOD and VEGF compared with the control group. However, the MDA level was significantly reduced. CONCLUSION: Batroxobin effectively improved the survival of random skin flaps.

Chinese Trauma Surgeon Association for management guidelines of vacuum sealing drainage application in abdominal surgeries-Update and systematic review.

Vacuum sealing drainage (VSD) is frequently used in abdominal surgeries. However, relevant guidelines are rare. Chinese Trauma Surgeon Association organized a committee composed of 28 experts across China in July 2017, aiming to provide an evidence-based recommendation for the application of VSD in abdominal surgeries. Eleven questions regarding the use of VSD in abdominal surgeries were addressed: (1) which type of materials should be respectively chosen for the intraperitoneal cavity, retroperitoneal cavity and superficial incisions? (2) Can VSD be preventively used for a high-risk abdominal incision with primary suture? (3) Can VSD be used in severely contaminated/infected abdominal surgical sites? (4) Can VSD be used for temporary abdominal cavity closure under some special conditions such as severe abdominal trauma, infection, liver transplantation and intra-abdominal volume increment in abdominal compartment syndrome? (5) Can VSD be used in abdominal organ inflammation, injury, or postoperative drainage? (6) Can VSD be used in the treatment of intestinal fistula and pancreatic fistula? (7) Can VSD be used in the treatment of intra-abdominal and extra-peritoneal abscess? (8) Can VSD be used in the treatment of abdominal wall wounds, wound cavity, and defects? (9) Does VSD increase the risk of bleeding? (10) Does VSD increase the risk of intestinal wall injury? (11) Does VSD increase the risk of peritoneal adhesion? Focusing on these questions, evidence-based recommendations were given accordingly. VSD was strongly recommended regarding the questions 2-4. Weak recommendations were made regarding questions 1 and 5-11. Proper use of VSD in abdominal surgeries can lower the risk of infection in abdominal incisions with primary suture, treat severely contaminated/infected surgical sites and facilitate temporary abdominal cavity closure.

Trauma care construction under the guidance of county-level trauma centers.

Severe trauma has the characteristics of complicated condition, multiple organs involved, limited auxiliary examinations, and difficulty in treatment. Most of the trauma patients were sent to primary hospitals to receive treatments. But the traditional mode of separate discipline management can easily lead to delayed treatment, missed or wrong diagnosis and high disability, which causes a high mortality in severe trauma patients. Therefore, if the primary hospitals, especially county-level hospitals (usually the top general hospital within the administrative region of a county), can establish a scientific and comprehensive trauma care system, the success rate of trauma rescue in this region can be greatly improved. On March 1st, 2013, Tiantai People's Hospital of Zhejiang Province, China set up a trauma care center, which integrated the pre-hospital and in-hospital trauma treatment procedures, and has achieved good economic and social benefits. Till March 1st, 2017, 1265 severe trauma patients (injury severity score >16) have been treated in this trauma center. The rescue success rate reached 95% and the delayed and/or missed diagnosis rate was less than 5%. Totally 86 severe cases of pelvic fractures with unstable hemodynamics were treated, and the success rate was 92%. The in-hospital emergency rescue response time is less than 3 min, and the time from definite diagnosis to surgery is within 35 min.

Effects of Linderae radix extracts on a rat model of alcoholic liver injury.

Traditional treatments have a poor effect on alcoholic liver diseases. Linderae radix (LR), the dried root of Lindera aggregata (Sims) Kosterm., has been frequently used in traditional Chinese medicine for treating various diseases, and has been shown to exhibit a protective effect on liver injury. In the present study, LR extracts were made using various solvents, and then administrated to rats to establish a model of ethanol-induced liver injury. The study aimed to investigate the therapeutic effects and potential mechanism of LR extracts on acute alcoholic liver injury. The serum levels of alanine aminotransferase (ALT), aspartate aminotransferase (AST), triglycercide (TG), cholesterol (TC), methane dicarboxylic aldehyde (MDA) and superoxide dismutase (SOD) were determined using an automatic biochemistry analyzer. In addition, pathological examination was performed by hematoxylin-eosin staining. The levels of MDA and SOD, and the expression levels of nuclear factor (NF)-κB, tumor necrosis factor (TNF)-α and interleukin (IL)-1ß in liver tissue were investigated immunohistochemically. The expression of cytochrome P450 2E1 (CYP2E1) mRNA was quantified by reverse transcription-quantitative polymerase chain reaction. The results indicated that LR extracts improved the histopathological status and decreased the serum levels of ALT, AST, TG, TC and MDA. Furthermore, the levels of MDA and inflammatory mediators (NF-κB, TNF-α and IL-1ß) were decreased in liver tissues, and the overexpression of CYP2E1 mRNA induced by ethanol treatment. LR extracts exhibited a protective effect on alcoholic liver injury and the mechanism may be associated with the anti-inflammatory and anti-oxidative action.

Association of a functional polymorphism in the MMP7 gene promoter with susceptibility to vulnerable carotid plaque in a Han Chinese population.

BACKGROUND: Matrix metalloproteinase-7 (MMP-7) may play an important role in the development of vulnerable carotid plaque. An A-to-G transition (-181A/G) in the promoter region of MMP7 is functional in vitro by altering the transcriptional activity of the gene. The aim of this study was to investigate the association between the MMP7 -181A/G polymorphism and vulnerable carotid plaque formation. METHODS: The authors enrolled 641 patients and divided them into three groups according to the carotid ultrasound examination: vulnerable plaque group (n=118), stable plaque group (n=385) and no plaque group (n=138). Traditional atherosclerosis risk factors were recorded and the MMP7 -181A/G polymorphism was genotyped by polymerase chain reaction-restriction fragment length polymorphism. RESULTS: In the multinomial logistic regression analysis, compared to the no plaque group, no relationship between MMP7 -181AG+GG genotypes and stable carotid plaque was observed [odds ratio (OR) 1.50; p=0.239]. However, the frequency of AG+GG genotypes was significantly higher in the vulnerable plaque group (OR 2.74; p=0.008). Age was a risk factor for plaque formation, while statin treatment can reduce the prevalence of atherosclerotic plaque. Additionally, using binary logistic regression analysis between the stable and vulnerable plaque groups, this MMP7 polymorphism was associated with vulnerable plaque independently of other factors [OR 1.83; 95% confidence interval 1.08- 3.11; p=0.026]. CONCLUSIONS: The MMP7 -181A/G polymorphism is associated with the development of vulnerable carotid plaques. Age is a risk factor for plaque formation, while statin therapy is associated with a decreased prevalence of carotid atheromatous plaques.