Background & Aims
Insulin resistance is strongly associated with non‐alcoholic fatty liver disease, a chronic, obesity–related liver disease. Increased endoplasmic reticulum (ER) stress plays an ...important role in the development of insulin resistance. In this study, we investigated the roles of miRNAs in regulating ER stress in the liver of rats with obesity.
Methods
We used miRNA microarray to determine the miRNA expression profiles in the liver of rats fed with a high fat diet (HFD). We used prediction algorithms and luciferase reporter assay to identify the target gene of miRNAs. To overexpress the miRNA miR‐30b or inhibit miR‐30b rats were injected with lentivirus particles containing PGLV3‐miR‐30b or PGLV3‐miR‐30b antimiR through tail vein. Hepatic steatosis was measured using transient elastography in human subjects.
Results
Our data showed that miR‐30b was markedly up‐regulated in the liver of HFD–treated rats. Bioinformatic and in vitro and in vivo studies led us to identify sarco(endo)plasmic reticulum Ca2+‐ATPase 2b (SERCA2b), as a novel target of miR‐30b. Overexpression of miR‐30b induced ER stress and insulin resistance in rats fed with normal diet, whereas inhibition of miR‐30b by miR‐30b antimiR suppressed ER stress and insulin resistance in HFD–treated rats. Finally, our data demonstrated that there was a positive correlation between serum miR‐30b levels and hepatic steatosis or homoeostasis model assessment of insulin resistance (HOMA‐IR) in human subjects.
Conclusions
Our findings suggest that miR‐30b represents not only a potential target for the treatment of insulin resistance, but also a non‐invasive disease biomarker of NAFLD.
Sinomenine (SIN) is the active ingredient of the Chinese herb Sinomenium acutum that has been used to treat rheumatoid arthritis (RA) for about 30 years in China. Marked expression of the alpha7 ...nicotinic acetylcholine receptor (α7nAChR) in the joint synovium of RA patients suggested a relationship between α7nAChR and RA. This study investigated the relationship between α7nAChR and RA development and the effects of SIN on α7nAChR expression in vivo and in vitro. Sprague-Dawley rats were injected with complete Freund’s adjuvant to induce arthritis and then treated with SIN or methotrexate (MTX) from day 0 to day 30. Four clinical parameters—paw volume, arthritic index (AI), serum TNF-α concentration, and erythrocyte sedimentation rate (ESR)—were measured. Splenic lymphocytes were isolated for Bacille Calmette Guerin (BCG) stimulation. α7nAChR expression in tissues and cells was examined by RT-PCR, western blot, immunofluorescence, flow cytometry, and immunohistochemistry. Cell proliferation was evaluated by the CCK-8 assay. The relationship between α7nAChR expression and the four clinical parameters was analyzed by single-factor correlation analysis. Our results showed that the paw volume, AI, TNF-α concentration, and ESR in adjuvant-induced arthritic (AIA) rats were reduced by SIN or MTX treatment. SIN decreased α7nAChR expression in tissues and cells compared to the model group, while MTX had no significant effect on α7nAChR expression. Moreover, there was a positive relationship between α7nAChR expression and paw swelling, AI, and TNF-α concentration. Splenic lymphocyte activation was accompanied by increased α7nAChR expression, while SIN treatment inhibited cell activation and downregulated α7nAChR expression. α7nAChR expression showed a positive correlation with the progression of RA in AIA rats that may involve lymphocyte activation. Different from MTX, the inhibition of SIN on α7nAChR expression might contribute to its antiarthritic effect, suggesting that SIN could be an important supplement to the treatment strategy for RA.
Background
Several studies have been performed to assess the relationship between hyperhomocysteinemia and type 2 diabetes mellitus (T2DM). However, inconsistent results have been obtained. ...Therefore, we performed this meta-analysis to address this knowledge gap.
Methods
We searched PubMed, Cochrane library, and EMBASE database for studies that evaluated the relationship between blood homocysteine (HCY) level and T2DM from inception to Jun 2019. The quality of all included studies was assessed by the Newcastle Ottawa Scale (NOS) and the Agency for Healthcare Research Quality (AHRQ). RevMan5.3 and Stata12.0 were used for data analyses.
Results
Twenty-five studies (including 1881 cases and 2868 controls) on blood HCY level in T2DM were pooled in our meta-analysis. The blood HCY level in the T2DM patients was significantly higher than in the healthy individuals (SMD = 0.63, 95% CI = 0.43–0.84, and
p
< 0.001,
I
2
= 89%,
p
< 0.001), ignores the effects of age, sex, cardiovascular and cerebrovascular disease conditions, and other comorbidity. Additionally, in T2DM patients with nephropathy or retinopathy, blood HCY level was also significantly higher than in those with only T2DM (SMD = 1.17, 95% CI = 0.76–1.58,
p
< 0.001;
I
2
= 90%,
p
< 0.001 and SMD = 0.91, 95% CI = 0.39–1.44,
p <
0.001;
I
2
= 82%,
p <
0.001, respectively).
Conclusion
Our meta-analysis revealed the HCY level in the blood of T2DM patients was significantly higher than those of the health subjects, especially in patients with diabetic nephropathy (DN) and diabetic retinopathy (DR).
Soft tissue sarcomas (STS) are a heterogeneous group of tumors, and approximately 40-50% of patients with STS develop metastatic disease. The median overall survival of those patients was 12 months ...and their 5-year survival rate was 8%. Therefore, study on more effective treatment, especially the targeting therapies, is urgently needed.
To evaluate the efficacy and safety of Endostar® combined with chemotherapy in patients with advanced STS.
A retrospective case-series study was conducted in Cancer Institute of PLA, Xinqiao Hospital. A total of 71 patients suffering from advanced STS (IIB - IV) were included, of whom 49 cases treated with chemotherapy alone were defined as the control group and the rest 22 cases treated with the traditional chemotherapy combined with Endostar® were defined as the test group. The short-term therapeutic effects including objective response rate (ORR), disease control rate (DCR) and safety were evaluated in the two groups. In the follow-up, progression-free survival (PFS) and overall survival (OS) were also observed.
In the test and control groups, the ORR was 18.2% and 12.2%, respectively (P = 0.767), and the DCR was 86.4% and 61.2%, respectively (P=0.034). The median time to progression in the test and control groups was 120 days and 70 days with significant difference (P = 0.017), while the median overall survival was 452 days and 286 days without significant difference (P = 0.503). The one-year survival rate in the test group and control group was 56.2% and 35.4%, respectively, while the two-year survival rate was 30.2% and 26.5%, respectively. No significant difference in the side effects was found between the two groups.
Endostar® combined with chemotherapy resulted in a higher DCR and longer PFS in the patients with advanced STS, and the toxicity was tolerable.
Superior vena cava (SVC) syndrome results from clear cell renal cell carcinoma and is a challenge in clinical practice due to its pathological complexity and a lack of research data. The current ...study presents a 49-year-old female with symptoms of exertional dyspnea and increased fatigue, which had persisted for 15 months, as well as bilateral edema in the lower limbs for two days. A transesophageal echocardiogram demonstrated a right atrial mass originating from the inferior vena cava (IVC; size, 14×8 cm) that caused a tricuspid inflow obstruction. Following a partial resection of the thrombus, a clear cell renal cell carcinoma was identified by histological examination. The patient received intensity-modulated radiation therapy following refusal of other therapeutic methods. The eleven-month follow-up indicated that the tumor on the kidney and IVC was stable. Intensity-modulated radiation therapy may be beneficial to patients with clear cell renal cell carcinoma and SVC syndrome. However, additional studies are required to obtain further data regarding the treatment of this syndrome.
Abdominal aortic aneurysm(AAA) is an inflammatory vascular disorder with high mortality.Accumulating evidence shows that toll-like receptor 2(TLR2) plays a critical role in the regulation of ...wound-repairing process after tissue injury.We wondered if TLR2 signaling contributed to the pathogenesis of AAA and that targeting TLR2 would attenuate AAA development and progression.In this study,enhanced expression of TLR2 and its ligands were observed in human AAA tissue.Neutralization of TLR2 protected against AAA development and caused established AAA to regress in mouse models of AAA.In addition,TLR2-deficient mice also failed to develop AAA.The prophylactic and therapeutic effects of blocking TLR2 were accompanied by a significant resolution of inflammation and vascular remodeling,as indicated by the decreased expression or activity of MMP-2/9,α-SMA,inflammatory cytokines,and transcription factors NF-κB,AP-1 and STAT1/3 in AAA tissue.Mechanistically,blocking TLR2 decreased the expression and interaction of TLR2 and several endogenousligands,which diminished chronic inflammation and vascular remodeling in the vascular tissue of AAA.Our studies indicate that the interactions between TLR2 and its endogenous ligands contribute to the pathogenesis of AAA and that targeting TLR2 offers great potential toward the development of therapeutic agents against AAA.
The distribution of the geometric distances of connected neurons is a practical factor underlying neural networks in the brain. It can affect the brain＇s dynamic properties at the ground level. ...Karbowski derived a power-law decay distribution that has not yet been verified by experiment. In this work, we check its validity using simulations with a phenomenological model. Based on the in vitro two- dimensional development of neural networks in culture vessels by Ito, we match the synapse number saturation time to obtain suitable parameters for the development process, then determine the distri-bution of distances between connected neurons under such conditions. Our simulations obtain a clear exponential distribution instead of a power-law one, which indicates that Karbowski＇s conclusion is invalid, at least for the case of in vitro neural network development in two-dimensional culture vessels.
The present study was designed to investigate whether a combination of four effective components derived from Sheng-mai san (SMXZF; ginsenoside Rb1: ginsenoside Rg1: DT-13: Schizandrol A as 6 : 9 : 4 ...: 5) could attenuate hydrogen peroxide (H2O2)-induced injury in PC12 cells, focusing on the Akt and MAPK pathways . The PC12 cells were exposed to H2O2 (400 μmol·L−1) for 1 h in the presence or absence of SMXZF pre-treatment for 24 h. Cell viability was measured by MTT assay. The efflux of lactate dehydrogenase (LDH), the intracellular content of malondialdehyde (MDA), the activities of superoxide dismutase (SOD), and caspase-3 were also determined. Cell apoptosis was measured by Hoechst 33342 staining and Annexin V-FITC/PI staining method. The expression of Bcl-2, Bax, cleaved caspase-3, Akt, and MAPKs were detected by Western blotting analyses. SMXZF pretreatment significantly increased the cell viability and SOD activity and improved the cell morphological changes, while reduced the levels of LDH and MDA at the concentrations of 0.1, 1 and 10 μg·mL−1. SMXZF also inhibited H2O2-induced apoptosis in PC12 cells. Moreover, SMXZF reduced the activity of caspase-3, up-regulated the protein ratio of Bcl-2 and Bax and inhibited the expression of cleaved caspase-3, p-Akt, p-p38, p-JNK and p-ERK1/2 in H2O2-induced PC12 cells. Co-incubation of Akt inhibitor or p38 inhibitor partly attenuated the protection of SMXZF against H2O2-injured PC12 cells. In conclusion, our findings suggested that SMXZF attenuated H2O2-induced injury in PC12 cells by inhibiting Akt and MAPKs signaling pathways, which might shed insights on its neuroprotective mechanism.
Hirota's bilinear approach is a very effective method to construct solutions for soliton systems. In terms of this method, the nonlinear equations can be transformed into linear equations, and can be ...solved by using perturbation method. In this paper, we study the bilinear Boussinesq equation and obtain its bilinear B\"{a}cklund transformation. Starting from this bilinear B\"{a}cklund transformation, we also derive its Lax pair and test its integrability.
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