MicroRNA-34 (miR-34) has been reported to be dysregulated in various human cancers and regarded as a tumor suppressive microRNA because of its synergistic effect with the well-known tumor suppressor p53. Along with the application of MRX34, the first tumor-targeted microRNA drug which based on miR-34a mimics, on phase I clinical trial (NCT01829971), the significance of miR-34 is increasingly recognized. miR-34 plays a crucial role on repressing tumor progression by involving in epithelial-mesenchymal transition (EMT) via EMT- transcription factors, p53 and some important signal pathways. Not only that, numerous preclinical researches revealed the giant potential of miR-34a on cancer therapy through diversiform nano-scaled delivery systems. Here, we provide an overview about the function of miR-34 in various cancers and the mechanism of miR-34 in tumor-associated EMT. Furthermore, its potential role as a microRNA therapeutic candidate is also discussed. Notwithstanding some obstacles existed, the extensive application prospect of miR-34 on oncotherapy cannot be neglected.

BackgroundRisk of type 2 diabetes mellitus (T2DM) is increased in metabolically obese but normal-weight people. However, we have limited knowledge of how to prevent T2DM in normal-weight people. We aimed to evaluate the association between triglyceride glucose (TyG) index and incident T2DM among normal-weight people in rural China.MethodsWe included data from 5706 people with normal body mass index (BMI) (18.5–23.9 kg/m2) without baseline T2DM in a rural Chinese cohort followed for a median of 6.0 years. A Cox proportional-hazard model was used to assess the risk of incident T2DM by quartiles of TyG index and difference in TyG index between follow-up and baseline (TyG-D), estimating hazard ratios (HRs) and 95% confidence intervals (CIs). A generalized additive plot was used to show the nonparametric smoothed exposure–response association between risk of T2DM and TyG index as a continuous variable. TyG was calculated as ln [fasting triglyceride level (mg/dl) × fasting plasma glucose level (mg/dl)/2].ResultsRisk of incident T2DM was increased with quartiles 2, 3 and 4 versus quartile 1 of TyG index (adjusted HR [aHR] 2.48 [95% CI 1.20–5.11], 3.77 [1.83–7.79], and 5.30 [2.21–12.71], P trend < 0.001 across quartiles of TyG index). Risk of incident T2DM was increased with quartile 4 versus quartile 1 of TyG-D (aHR 3.91 [2.22–6.87]). The results were consistent when analyses were restricted to participants without baseline metabolic syndrome and impaired fasting glucose level. The generalized additive plot showed cumulative increased risk of T2DM with increasing TyG index.ConclusionsRisk of incident T2DM is increased with increasing TyG index among rural Chinese people, so the index might be an important indicator for identifying people at high risk of T2DM.

Coronary heart disease (CHD) is the second leading cause of cardiovascular death in the Chinese population. It accounts for 22% of cardiovascular deaths in urban areas and 13% in rural areas. Although mortality from CHD in China is relatively low compared with Western levels, the burden of CHD has been increasing. This is partly because of a worsening profile of risk factors, such as an increased prevalence of hypertension, hyperlipidaemia, overweight/obesity, diabetes, etc and partly because of an increase in the aged population. Large-scale, randomised controlled trials on thrombolytic, blood-pressure-lowering, antiplatelet and blood-cholesterol-lowering treatment as well as cardiac intervention have been conducted for Chinese patients with myocardial infarction. The studies provide important information for the prevention and management of chronic CHD and acute myocardial infarction in the Chinese population.

The purpose of this study was to permit bone marrow mesenchymal stem cells (BMSCs) to reach their full potential in the treatment of chronic wounds. A biocompatible multifunctional crosslinker based temperature sensitive hydrogel was developed to deliver BMSCs, which improve the chronic inflammation microenvironments of wounds. A detailed in vitro investigation found that the hydrogel is suitable for BMSC encapsulation and can promote BMSC secretion of TGF-β1 and bFGF. In vivo, full-thickness skin defects were made on the backs of db/db mice to mimic diabetic ulcers. It was revealed that the hydrogel can inhibit pro-inflammatory M1 macrophage expression. After hydrogel association with BMSCs treated the wound, significantly greater wound contraction was observed in the hydrogel + BMSCs group. Histology and immunohistochemistry results confirmed that this treatment contributed to the rapid healing of diabetic skin wounds by promoting granulation tissue formation, angiogenesis, extracellular matrix secretion, wound contraction, and re-epithelialization. These results show that a hydrogel laden with BMSCs may be a promising therapeutic strategy for the management of diabetic ulcers.

Metastatic breast cancer is the second leading cause of cancer-related deaths amongst women. Triple-negative breast cancer (TNBC) is a highly aggressive subcategory of breast cancer and currently lacks well-defined molecular targets for effective targeted therapies. Disease relapse, metastasis, and drug resistance render standard chemotherapy ineffective in the treatment of TNBC. Since previous studies coupled β3 integrin to epithelial-mesenchymal transition (EMT) and metastasis, we exploited β3 integrin as a therapeutic target to treat TNBC by delivering β3 integrin siRNA via lipid ECO-based nanoparticles (ECO/siβ3). Treatment of TNBC cells with ECO/siβ3 was sufficient to effectively silence β3 integrin expression, attenuate TGF-β-mediated EMT and invasion, restore TGF-β-mediated cytostasis, and inhibit 3-dimensional organoid growth. Modification of ECO/siβ3 nanoparticles with an RGD peptide via a PEG spacer enhanced siRNA uptake by post-EMT cells. Intravenous injections of RGD-targeted ECO/siβ3 nanoparticles in vivo alleviated primary tumor burden, and more importantly, significantly inhibited metastasis. Mice bearing orthotopic, TGF-β-pre-stimulated MDA-MB-231 tumors that were treated with RGD-targeted ECO/siβ3 nanoparticles were free of metastases and relapse after primary tumor resection and 4 weeks after release from the treatment, in comparison to untreated mice. Collectively, these results highlight ECO/siβ3 nanoparticles as a promising therapeutic regimen to combat TNBC.

The development of an effective vaccine is critical for prevention of a Middle East respiratory syndrome coronavirus (MERS-CoV) pandemic. Some studies have indicated the receptor-binding domain (RBD) protein of MERS-CoV spike (S) is a good candidate antigen for a MERS-CoV subunit vaccine. However, highly purified proteins are typically not inherently immunogenic. We hypothesised that humoral and cell-mediated immunity would be improved with a modification of the vaccination regimen. Therefore, the immunogenicity of a novel MERS-CoV RBD-based subunit vaccine was tested in mice using different adjuvant formulations and delivery routes. Different vaccination regimens were compared in BALB/c mice immunized 3 times intramuscularly (i.m.) with a vaccine containing 10 µg of recombinant MERS-CoV RBD in combination with either aluminium hydroxide (alum) alone, alum and polyriboinosinic acid (poly I:C) or alum and cysteine-phosphate-guanine (CpG) oligodeoxynucleotides (ODN). The immune responses of mice vaccinated with RBD, incomplete Freund’s adjuvant (IFA) and CpG ODN by a subcutaneous (s.c.) route were also investigated. We evaluated the induction of RBD-specific humoral immunity (total IgG and neutralizing antibodies) and cellular immunity (ELISpot assay for IFN-γ spot-forming cells and splenocyte cytokine production). Our findings indicated that the combination of alum and CpG ODN optimized the development of RBD-specific humoral and cellular immunity following subunit vaccination. Interestingly, robust RBD-specific antibody and T-cell responses were induced in mice immunized with the rRBD protein in combination with IFA and CpG ODN, but low level of neutralizing antibodies were elicited. Our data suggest that murine immunity following subunit vaccination can be tailored using adjuvant combinations and delivery routes. The vaccination regimen used in this study is promising and could improve the protection offered by the MERS-CoV subunit vaccine by eliciting effective humoral and cellular immune responses.

This systematic review aimed to evaluate the long-term (≥ 5 years) outcomes of bariatric surgery on diabetes remission, microvascular and macrovascular events, and mortality among type 2 diabetes (T2D) patients. Ten articles (one randomized controlled trial and nine cohorts) met the inclusion criteria and were included in this review. Pooled estimates of nine cohort studies showed that surgery significantly increased the diabetes remission (relative risk (RR) = 5.90; 95% CI 3.75-9.28), reduced the microvascular (RR = 0.37; 95% CI = 0.30-0.46) and macrovascular events (RR = 0.52; 95% CI 0.44-0.61), and mortality (RR = 0.21; 95% CI 0.20-0.21) as compared to non-surgical treatment. Available evidence suggests better remission and lower risks of microvascular and macrovascular disease and mortality in the surgery group as compared to non-surgical treatment group in T2D patients after at least 5 years of follow-up.

Novel antigen responsive hydrogels were prepared by using polymerizable antibody Fab′ fragment from monoclonal anti‐fluorescein BDC1 antibody (IgG2a). To form Fab′ containing hydrogels, the polymerizable Fab′ fragment was copolymerized with N‐isopropylacrylamide (NIPAAm) and N,N′‐methylenebis(acrylamide) (MBAAm; crosslinker) using redox initiators. The thermosensitivity of the hydrogels decreased with increasing Fab′ fragment content. The antigen responsiveness of the hydrogels depended on the Fab′ content, pH, and temperature. When the hydrogels were alternately exposed to antigens fluorescein (FL) and polyamidoamine dendrimer (PAMAM)‐fluorescein (FD), significant reversible volume changes were observed for the hydrogel containing 50% (w/w) Fab′ fragment at 33.7 and 36.8 °C in acetate buffer (10 mM, pH 5.0), respectively, but not at 27.7 °C or in PBS buffer (10 mM, pH 7.4). No noticeable reversible volume changes were observed with pure PNIPAAm hydrogel and the gel containing 10% (w/w) Fab′ fragment.Structure of Fab′ containing hydrogels.magnified imageStructure of Fab′ containing hydrogels.