Current Signal Transduction Therapy - Volume 9, Issue 2, 2014

Hydrogen sulfide (H2S) is regarded as one of the air pollutants with a rotten egg smell. However, it is recently discovered that endogenous H2S has important physiological and pathological functions. Cystathionine- β synthase (CBS) and cystathionine- γ lyase (CSE) play key roles in the synthesis of H2S, and CSE is also a major H2S-formation enzyme in the cardiovascular system. Vascular inflammation is one of the most important pathological processes in a variety of vascular diseases. The present review aimed at exploring the role of hydrogen sulfide and its signaling in vascular inflammation during vascular diseases including atherosclerosis, systemic hypertension, pulmonary hypertension (PAH), and vascular balloon injury.

The maintenance of pancreatic β-cells normal functioning is crucial for insulin production and glucose homeostasis. Inadequate insulin secretion due to β-cell dysfunction can lead to different types of diabetes mellitus. Though it is widely recognized that both environmental and genetic factors play important roles, the exact molecular mechanism that leads to β -cell failure is still unclear. MicroRNAs (miRNAs) regulate numerous physiological and pathophysiological processes at the epigenetic level. miRNAs have been reported to participate in the process of pancreatic development and insulin biosynthesis. Some miRNAs may control insulin secretion and exocytosis through regulating ATP/ADP ratio. In this review, we will summarize the pathological roles of miRNAs in β-cell dysfunction and briefly discuss miRNAs as possible biomarkers and potential pharmaceutical target for diabetes mellitus.

Glioblastoma, a highly lethal brain tumor, features extensive heterogeneity at the cellular and molecular levels. The discovery of glioma stem cells (GSCs) supports a new paradigm in tumor biology and therapeutic targeting. GSCs contribute to the cellular origin of primary gliomas and the recurrence of malignant gliomas after traditional treatments. A growing body of evidence suggests that GSCs, just as the bulk tumor cells, are heterogeneous with phenotypic and genetic complexity. Heterogeneous GSCs may add to glioblastoma heterogeneity and impact response to current therapies. A better understanding of GSC heterogeneity is required to facilitate the design of more effective therapies against this highly malignant brain tumor.

Signal transduction has been acknowledged to be involved in various cell biological processes. And it is proved that multiple signaling pathways have been associated with the development and progression of pancreatic cancer, which remains one of the most devastating human diseases. Newly developed drugs targeting these aberrant signaling pathways show bright prospect in improving the therapeutic efficacy and outcome for patients with pancreatic cancer. Here we overview the pancreatic cancer related signaling pathway disorders and the corresponding promising targeted therapeutic regimens.

Background: The association between gastroesophageal reflux disease (GERD) and hemodialysis (HD) is unclear. We aimed to determine the prevalence of GERD in HD patients and to identify the risk factors and effects of GERD in this patient population. Methods: This retrospective study involved 432 HD patients who completed a questionnaire including a GERD symptom assessment scale (QUEST). Clinical data were obtained by interviewing the patients and/or reviewing their medical records. Results: GERD was diagnosed in 141 (32.64%) of the 432 HD patients by using a structured questionnaire scoring system. Multivariate logistic regression analysis revealed that low urine volume (odds ratio [OR]: 1.619, 95% confidence interval [CI]: 1.046–2.505; P = 0.031), high serum creatinine level (OR: 1.694, 95% CI: 1.011–2.839; P = 0.045), angiotensin receptor blocker (ARB)/angiotensin-converting enzyme inhibitor (ACEI) administration (OR: 1.767, 95% CI: 1.13–2.746; P = 0.011) and the intradialytic complications of excessive hunger (OR: 1.652, 95% CI: 1.067–2.559; P = 0.024), heartburn (OR: 6.235, 95% CI: 2.606–14.920; P = 0.000) and tinnitus (OR: 1.606, 95% CI: 1.029–2.507; P = 0.037) were independent predictors of GERD, as detected using QUEST. The Spearman rank correlation analysis showed that sodium bicarbonate consumption was positively correlated with serum total carbon dioxide level (r = 0.127, P = 0.008), interdialytic weight gain (IDWG; r = 0.189, P = 0.000) and IDWG% (IDWG/estimated dry weight; r = 0.166, P = 0.001). Conclusions: The prevalence of GERD is higher in patients undergoing HD in our center than in the general population. The risk factors for GERD in hemodialysis patients were low urine volume (<0.1 l/d), high serum creatinine level (>9 mg/dl), ARB/ACEI administration and intradialytic hunger, heartburn and tinnitus. HD patients with GERD may take excessive sodium bicarbonate, which increases IDWG%. Awareness of GERD and administration of PPIs were low in HD patients. Routine PPI treatment would provide clinical benefits by reducing GERD symptoms, sodium bicarbonate consumption and IDWG%.

Objectives: As a selective matrix metalloproteinase inhibitor, MMI-166 specifically inhibits MMP-2 and MMP-9 activity and represses tumor invasion and metastasis. Previous studies show that MMI-166 has an anti-metastatic role in a variety of tumors. However, it still remains unclear about the exact effect of MMI-166 on human pancreatic cancer. Methods: In this study, we showed firstly MMI-166 induced proliferation inhibition and apoptosis of SW1990 human pancreatic cancer cells in both dose- and time-dependent manners in vitro. We successfully established a human pancreatic cancer xenograft model in nude mice and verified the inhibition effect of MMI-166 on MMP-2 and MMP-9. Results: More importantly, by using this model, we further demonstrated MMI-166 suppressed growth of SW1990 pancreatic cells xenograft in vivo by inducing cells apoptosis. In addition, we examined the expression of a series of apoptosis-related proteins and found MMI-166 inhibited the expression of c-Myc. Conclusion: Our work demonstrates that MMI-166 may be of therapeutic value in the treatment of pancreatic cancer.

Cancer cell metabolism plays an important role in the progression of lung cancer. It is characterized through a shift from an oxidative to a glycolytic bioenergetics pathway, a phenomenon referred to as the warburg effect. However, the deregulation of miRNAs contributing to the warburg effect and to cancer cell metabolism is still unknown. In the present study, the results demonstrate that the expression of miR-202 is significantly decreased, and it induces a metabolic shift in lung cancer cells. miR-202 exerts this function through targeting HK2, resulting in the increase of glucose uptake and lactate production. The altered metabolism induced by miR-202 leads to cancer cell growth. These studies demonstrated that miR-202 may be involved in the metabolic shift via targeting HK2 in lung cancer cells.

Background: To evaluate the effects of aqueous Cortex Lycii Radicis (CLR) extracts on diabetic nephrology in a streptozotocin-induced diabetic nephropathy rat model, and to explore the underlying mechanisms of CLR action. Methods: We induced diabetes mellitus via a single intravenous streptozotocin injection (30 mg/kg) and subsequent high-fat diet for 3 weeks in male Sprague Dawley rats. Rats that developed diabetes mellitus were randomized to receive normal saline (vehicle, n=10), low-dose CLR (15 g/kg/day, n=10), or high-dose CLR (30 g/kg/day, n=10), and rosiglitazone (2 mg/kg/day, n=10) daily for 8 weeks. In addition, 10 normal rats served as controls. Kidneys were removed to evaluate histological renal glomeruli alterations using periodic acid–Schiff (PAS) staining. Results: Fructosamine, and blood urea nitrogen concentrations, as well as the urinary albumin excretion rate (AER), were increased in vehicle-treated diabetic rats compared to control rats (P<0.05). These parameters decreased upon CLR treatment, particularly at low-dosage CLR (P<0.05). Morphologic observations showed that high-dosage CLR markedly attenuated diabetes-associated renal injury. The renal protective effects of CLR may be mediated by downregulation of cytokine expression, including TGF-α and interleukin 6. Conclusion: CLR accelerates functional and histological kidney recovery, thereby delaying diabetic nephropathy progression. Therefore, it may be a novel therapeutic approach for the treatment of diabetic nephrology.