Cellular senescence in cancer: from mechanisms to detection

Senescence refers to a cellular state featuring a stable cell‐cycle arrest triggered in response to stress. This response also involves other distinct morphological and intracellular changes including alterations in gene expression and epigenetic modifications, elevated macromolecular damage, metabolism deregulation and a complex pro‐inflammatory secretory phenotype. The initial demonstration of oncogene‐induced senescence in vitro established senescence as an important tumour‐suppressive mechanism, in addition to apoptosis. Senescence not only halts the proliferation of premalignant cells but also facilitates the clearance of affected cells through immunosurveillance. Failure to clear senescent cells owing to deficient immunosurveillance may, however, lead to a state of chronic inflammation that nurtures a pro‐tumorigenic microenvironment favouring cancer initiation, migration and metastasis. In addition, senescence is a response to post‐therapy genotoxic stress. Therefore, tracking the emergence of senescent cells becomes pivotal to detect potential pro‐tumorigenic events. Current protocols for the in vivo detection of senescence require the analysis of fixed or deep‐frozen tissues, despite a significant clinical need for real‐time bioimaging methods. Accuracy and efficiency of senescence detection are further hampered by a lack of universal and more specific senescence biomarkers. Recently, in an attempt to overcome these hurdles, an assortment of detection tools has been developed. These strategies all have significant potential for clinical utilisation and include flow cytometry combined with histo‐ or cytochemical approaches, nanoparticle‐based targeted delivery of imaging contrast agents, OFF‐ON fluorescent senoprobes, positron emission tomography senoprobes and analysis of circulating SASP factors, extracellular vesicles and cell‐free nucleic acids isolated from plasma. Here, we highlight the occurrence of senescence in neoplasia and advanced tumours, assess the impact of senescence on tumorigenesis and discuss how the ongoing development of senescence detection tools might improve early detection of multiple cancers and response to therapy in the near future

Cerebrospinal fluid neurofilament dynamic profiles predict cognitive progression in individuals with de novo Parkinson’s disease

BackgroundNeurofilament light chain protein (NfL) in cerebrospinal fluid (CSF) reflects the severity of neurodegeneration, with its altered concentrations discovered in Parkinson’s disease (PD) and Parkinson’s disease dementia (PD-D).ObjectiveTo determine whether CSF NfL, a promising biomarker of neuronal/axonal damage, can be used to monitor cognitive progression in de novo Parkinson’s disease and predict future cognitive decline.MethodsA total of 259 people were recruited in this study, including 85 healthy controls (HC) and 174 neonatal PD patients from the Parkinson’s Progression Markers Initiative (PPMI). Multiple linear regression and linear mixed effects models were used to examine the associations of baseline/longitudinal CSF NfL with cognitive decline and other CSF biomarkers. Kaplan–Meier analysis and log-rank test were used to compare the cumulative probability risk of cognition progression during the follow-up. Multivariate cox regression was used to detect cognitive progression in de novo PD.ResultsWe found PD patients with mild cognitive impairment (PD-MCI) was higher than with normal cognition (PD-NC) in terms of CSF NfL baseline levels (p = 0.003) and longitudinal increase rate (p = 0.034). Both baseline CSF NfL and its rate of change predicted measurable cognitive decline in de novo PD (MoCA, β = −0.010, p = 0.011; β = −0.0002, p < 0.001, respectively). The predictive effects in de novo PD patients aged >65, male, ill-educated (<13 years) and without carrying Apolipoprotein E ε4 (APOE ε4) seemed to be more obvious and reflected in more domains investigated. We also observed that CSF NfL levels predicted progression in de novo PD patients with different cognitive diagnosis and amyloid status. After an average follow-up of 6.66 ± 2.54 years, higher concentration above the median of baseline CSF NfL was associated with a future high risk of PD with dementia (adjusted HR 2.82, 95% CI: 1.11–7.20, p = 0.030).ConclusionOur results indicated that CSF NfL is a promising prognostic predictor of PD, and its concentration and dynamics can monitor the severity and progression of cognitive decline in de novo PD patients

Anticarcinogenic potentials of tea catechins

Catechins are a cluster of polyphenolic bioactive components in green tea. Anticarcinogenic effects of tea catechins have been reported since the 1980s, but it has been controversial. The present paper reviews the advances in studies on the anticarcinogenic activities of tea and catechins, including epidemiological evidence and anticarcinogenic mechanism. Tea catechins showed antagonistic effects on many cancers, such as gynecological cancers, digestive tract cancers, incident glioma, liver and gallbladder cancers, lung cancer, etc. The mechanism underlying the anticarcinogenic effects of catechins involves in inhibiting the proliferation and growth of cancer cells, scavenging free radicals, suppressing metastasis of cancer cells, improving immunity, interacting with other anticancer drugs, and regulating signaling pathways. The inconsistent results and their causes are also discussed in this paper

A Meta-Analysis of Randomized Controlled Trials of Yiqi Yangyin Huoxue Method in Treating Diabetic Nephropathy

Objective. The purpose of this systematic review is to evaluate the evidence of Yiqi Yangyin Huoxue Method for diabetic nephropathy. Methods. 11 electronic databases, through September 2015, were searched to identify randomized controlled trials of Yiqi Yangyin Huoxue Method for diabetic nephropathy. The quality of the included trials was assessed using the Jadad scale. Results. 26 randomized controlled trials were included in our review. Of all the included trials, most of them were considered as high quality. The aggregated results suggested that Yiqi Yangyin Huoxue Method is beneficial to diabetic nephropathy in bringing down the microalbuminuria (SMD = −0.98, 95% CI −1.22 to −0.74), serum creatinine (SMD = −0.56, 95% CI −0.93 to −0.20), beta-2 microglobulin (MD = 0.06, 95% CI 0.01 to 0.12), fasting plasma glucose (MD = −0.35, 95% CI −0.62 to −0.08), and 2-hour postprandial blood glucose (MD = 1.13, 95% CI 0.07 to 2.20), but not in decreasing blood urea nitrogen (SMD = −0.72, 95% CI −1.47 to 0.02) or 2-hour postprandial blood glucose (SMD = −0.48, 95% CI −1.01 to 0.04). Conclusions. Yiqi Yangyin Huoxue Method should be a valid complementary and alternative therapy in the management of diabetic nephropathy, especially in improving UAER, serum creatinine, fasting blood glucose, and beta-2 microglobulin. However, more studies with long follow-up are warrant to confirm the current findings

In vitro anti-Helicobacter pylori activity and the underlining mechanism of an empirical herbal formula – Hezi Qingyou

BackgroundHelicobacter pylori (H. pylori) is thought to primarily colonize the human stomach and lead to various gastrointestinal disorders, such as gastritis and gastric cancer. Currently, main eradication treatment is triple or quadruple therapy centered on antibiotics. Due to antibiotic resistance, the eradication rate of H. pylori is decreasing gradually. Therefore, searching for anti-H. pylori drugs from herbal sources has become a strategy for the treatment. Our team proposed a Hezi Qingyou Formula (HZQYF), composed of Chebulae Fructus, Ficus hirta Vahl and Cloves, and studied its anti-H. pylori activity and mechanism.MethodsChemical components of HZQYF were studied using UHPLC–MS/MS and HPLC. Broth microdilution method and agar dilution method were used to evaluate HZQYF’s antibacterial activity. The effects of HZQYF on expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF), and flagellar genes (flaA, flaB) were explored using Reverse Transcription-quantitative Polymerase Chain Reaction (RT-qPCR) technology. Effects on morphology and permeability of the extracellular membrane were studied using scanning electron microscopy (SEM) and N-phenylnaphthalen-1-amine (NPN) uptake. Effect on urease activity was studied using a urease kinetics analysis in vitro. Immunofluorescence staining method was used to examine the effect on adhesion. Western blot was used to examine the effect on cagA protein.ResultsMinimum inhibitory concentration (MIC) values of the formula against H. pylori clinical strains and standard strains were 80–160 μg/mL, and minimum bactericidal concentration (MBC) values were 160–320 μg/mL. The formula could down-regulate the expression of adhesion genes (alpA, alpB, babA), urease genes (ureE, ureF) and flagellar genes (flaA, flaB), change the morphology of H. pylori, increase its extracellular membrane permeability, and decrease its urease activity.ConclusionPresent studies confirmed that HZQYF had promising in vitro anti-H. pylori activities and demonstrated its possible mechanism of action by down-regulating the bacterial adhesion, urease, and flagellar gene expression, which provided scientific bases for further clinical investigations