In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
LC3; autolysosome; autophagosome; flux; lysosome; phagophore; stress; vacuole
Xenon is one of noble gases and has been recognized as an anesthetic for more than 50 years. Xenon possesses many of the characteristics of an ideal anesthetic, but it is not widely applied in clinical practice mainly because of its high cost. In recent years, numerous studies have demonstrated that xenon as an anesthetic can exert neuroprotective and cardioprotective effects in different models. Moreover, xenon has been applied in the preconditioning, and the neuroprotective and cardioprotective effects of xenon preconditioning have been investigated in a lot of studies in which some mechanisms related to these protections are proposed. In this review, we summarized these mechanisms and the biological effects of xenon preconditioning.
Xenon; Preconditioning; Neuroprotection; Cardioprotection; Mechanism
Aptamers are single-stranded oligonucleotides of DNA or RNA that bind to target molecules with high affinity and specificity. Typically, aptamers are generated by an iterative selection process, called systematic evolution of ligands by exponential enrichment (SELEX). Recent advancements in SELEX technology have extended aptamer selection from comparatively simple mixtures of purified proteins to whole living cells, and now cell-based SELEX (or cell-SELEX) can isolate aptamers that bind to specific target cells. Combined with nanotechnology, microchips, microfluidic devices, RNAi and other advanced technologies, cell-SELEX represents an integrated platform providing ultrasensitive and highly specific tools for clinical medicine. In this review, we describe the recent progress made in the application of cell-SELEX for diagnosis, therapy and biomarker discovery.
aptamer; SELEX; molecular medicine
Metal oxide gas sensors are predominant solid-state gas detecting devices for domestic, commercial and industrial applications, which have many advantages such as low cost, easy production, and compact size. However, the performance of such sensors is significantly influenced by the morphology and structure of sensing materials, resulting in a great obstacle for gas sensors based on bulk materials or dense films to achieve highly-sensitive properties. Lots of metal oxide nanostructures have been developed to improve the gas sensing properties such as sensitivity, selectivity, response speed, and so on. Here, we provide a brief overview of metal oxide nanostructures and their gas sensing properties from the aspects of particle size, morphology and doping. When the particle size of metal oxide is close to or less than double thickness of the space-charge layer, the sensitivity of the sensor will increase remarkably, which would be called “small size effect”, yet small size of metal oxide nanoparticles will be compactly sintered together during the film coating process which is disadvantage for gas diffusion in them. In view of those reasons, nanostructures with many kinds of shapes such as porous nanotubes, porous nanospheres and so on have been investigated, that not only possessed large surface area and relatively mass reactive sites, but also formed relatively loose film structures which is an advantage for gas diffusion. Besides, doping is also an effective method to decrease particle size and improve gas sensing properties. Therefore, the gas sensing properties of metal oxide nanostructures assembled by nanoparticles are reviewed in this article. The effect of doping is also summarized and finally the perspectives of metal oxide gas sensor are given.
metal oxide; gas sensing; nanostructure; size effect; doping
Chronic pain is a major health concern that affects millions of people. There are no adequate long-term therapies for chronic pain sufferers, leading to significant cost for both society and the individual. The most commonly used therapy for chronic pain is the application of opioid analgesics and nonsteroidal anti-inflammatory drugs, but these drugs can lead to addiction and may cause side effects. Further studies of the mechanisms of chronic pain have opened the way for development of new treatment strategies, one of which is gene therapy. The key to gene therapy is selecting safe and highly efficient gene delivery systems that can deliver therapeutic genes to overexpress or suppress relevant targets in specific cell types. Here we review several promising viral vectors that could be applied in gene transfer for the treatment of chronic pain and further discuss the possible mechanisms of genes of interest that could be delivered with viral vectors for the treatment of chronic pain.
AIM: To analyze the possible protective role of Arctium lappa L. (AL) in a murine model of ulcerative colitis (UC).
METHODS: BALB/c mice were administered 100 mg/kg AL powder orally each day. After 7 d, colitis was induced by administration of dextran sulfate sodium (DSS) (5% W/V) in drinking water for a further 8 consecutive days. Diarrhea and bloody stools as well as colonic histology were observed. The level of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) in colonic sections were detected by immunohistochemistry.
RESULTS: There were significant differences in mean body weight values and disease activity indices between controls and AL-treated animals. Moreover, the histological findings showed that AL treatment can prevent mucosal edema, submucosal erosions, ulceration, inflammatory cell infiltration and colon damage. In addition, immunohistochemistry analysis showed that the levels of the inflammatory cytokines, IL-6 and TNF-α were also decreased in AL-treated groups.
CONCLUSION: We suggest that AL can prevent intestinal damage and decrease inflammatory cytokines in mice with DSS-induced colitis. Thus, AL could prove to be a useful food for UC.
Arctium lappa L.; Colitis; Cytokine; Inflammatory bowel disease; Ulcerative colitis
Liver fibrosis is a common histological process to develop into cirrhosis in various chronic liver diseases including chronic hepatitis and fatty liver. Therefore anti-liver fibrosis is very important strategy to treat chronic liver diseases. Fuzheng Huayu (FZHY), a preparation containing herbs such as Radix Salvia Miltiorrhizae, Cordyceps, Semen Persicae, was formulated on the basis of Chinese medicine theory in treating liver fibrosis and was approved. Pharmacological studies and clinical trials demonstrate that FZHY has a significant effect against liver fibrosis and that many of the pharmacological actions are attributable to the effect. This article reviews the effects and actions of FZHY, in particular the effects observed from clinical trials in treating liver fibrosis caused by chronic hepatitis B and the actions on inhibition of hepatic stellate cell activation, protection of hepatocytes and inhibition of hepatic sinusoidal capillarization. This article also reviews the coordinated effects of the constituent herbs of FZHY and the actions of their active compounds such as salvianonic acid B (SA-B) on liver fibrosis.
Epidemiological studies have found that low 25-hydroxyvitamin D levels may be associated with coronary risk factors and adverse cardiovascular outcomes. Additionally, vitamin D deficiency causes an increase in parathyroid hormone, which increases insulin resistance and is associated with diabetes, hypertension, inflammation, and increased cardiovascular risk. In this review, we analyze the association between vitamin D supplementation and the reduction in cardiovascular disease. The role of vitamin D deficiency in cardiovascular morbidity and mortality is still controversial, and larger scale, randomized placebo controlled trials are needed to investigate whether oral vitamin D supplementation can reduce cardiovascular risk. Given the low cost, safety, and demonstrated benefit of higher 25-hydroxyvitamin D levels, vitamin D supplementation should become a public health priority for combating common and costly chronic cardiovascular diseases.
Cardiovascular disease; Morbidity; Mortality; Review; Vitamin D
Hydrogen sulfide (H2S) is the third endogenous signaling gasotransmitter, following nitric oxide and carbon monoxide. It is physiologically generated by cystathionine-γ-lyase, cystathionine-β-synthase, and 3-mercaptopyruvate sulfurtransferase. H2S has been gaining increasing attention as an important endogenous signaling molecule because of its significant effects on the cardiovascular and nervous systems. Substantial evidence shows that H2S is involved in aging by inhibiting free-radical reactions, activating SIRT1, and probably interacting with the age-related gene Klotho. Moreover, H2S has been shown to have therapeutic potential in age-associated diseases. This article provides an overview of the physiological functions and effects of H2S in aging and age-associated diseases, and proposes the potential health and therapeutic benefits of H2S.
This systematic review aims to evaluate current evidence for the benefit and side effect of oral Panax notoginseng preparation for coronary heart disease (CHD). We included 17 randomized clinical trials (17 papers and 1747 participants). Comparing with no intervention on the basis of conventional therapy, oral Panax notoginseng did not show significant effect on reducing cardiovascular events, but it could alleviate angina pectoris (including improving the symptoms of angina pectoris [RR 1.20; 95% CI 1.12 to 1.28; 7 trials, n = 791], improving electrocardiogram [RR 1.35; 95% CI 1.19 to 1.53; 8 trials, n = 727], decreasing the recurrence of angina pectoris [RR 0.38; 95% CI 0.16 to 0.94; 1 trials, n = 60], duration of angina pectoris [RR −1.88; 95% CI −2.08 to −1.69; 2 trials, n = 292], and dosage of nitroglycerin [MD −1.13; 95% CI −1.70 to −0.56; 2 trials, n = 212]); oral Panax notoginseng had no significant difference compared with isosorbide dinitrate on immediate effect for angina pectoris [RR 0.96; 95% CI 0.81 to 1.15; 1 trial, n = 80]. In conclusion, oral Panax notoginseng preparation could relieve angina pectoris related symptoms. However, the small sample size and potential bias of most trials influence the convincingness of this conclusion. More rigorous trials with high quality are needed to give high level of evidence, especially for the potential benefit of cardiovascular events.
New-generation retroviral vectors have potential applications in vaccination and gene therapy. Foamy viruses are particularly interesting as vectors, because they are not associated to any disease. Vector research is mainly based on primate foamy viruses (PFV), but cats are an alternative animal model, due to their smaller size and the existence of a cognate feline foamy virus (FFV). The potential of replication-competent (RC) FFV vectors for vaccination and replication-deficient (RD) FFV-based vectors for gene delivery purposes has been studied over the past years. In this review, the key achievements and functional evaluation of the existing vectors from in vitro cell culture systems to out-bred cats will be described. The data presented here demonstrate the broad application spectrum of FFV-based vectors, especially in pathogen-specific prophylactic and therapeutic vaccination using RD vectors in cats and in classical gene delivery. In the cat-based system, FFV-based vectors provide an advantageous platform to evaluate and optimize the applicability, efficacy and safety of foamy virus (FV) vectors, especially the understudied aspect of FV cell and organ tropism.
retrovirus vector; foamy virus; vaccine vector; gene therapy vector; animal model; spumaretrovirus; replication-deficient vector; replication-competent vector
There are controversies on the association between interleukin-13 (IL-13) +1923C/T polymorphism (rs1295686) and the risk of asthma. We performed this study to assess the association by the method of meta-analysis. A systematic search current to October 16, 2012, was conducted using PubMed, EMBASE, and China National Knowledge Infrastructure (CNKI) and identified ten studies comprising 13698 cases and 38209 controls. The pooled odds ratios (ORs) with 95% confidence intervals (CIs) were calculated. There was a significant association between IL-13 +1923C/T polymorphism and asthma risk in codominant model. When stratified by ethnicity, IL-13 +1923C/T polymorphism remained significantly associated with higher asthma risk in Asians and Caucasians. In the subgroup analysis by study quality, a significantly increased asthma risk was observed in high quality studies. Sensitivity analysis and cumulative analysis further strengthened the validity of the results. No publication bias was found in this meta-analysis. In conclusion, results from this meta-analysis suggested that IL-13 +1923C/T polymorphism was a risk factor of asthma.
Telangiectatic osteosarcoma is a rare variant of osteosarcoma and hence its occurrence, presentation, and prognosis are poorly understood. With advancements in technology and available treatment options, the scenario of its diagnosis, management, and outcome has changed. Chemotherapy with surgery was challenged previously, but has now been proved to be beneficial. We reviewed the available literature and compared results to define the characteristics of the disease, its presentation, radiographic and pathologic features, optimal treatment, and prognosis.
telangiectatic osteosarcoma; osteosarcoma; radiology
Because magnetic resonance imaging (MRI) contrast agents play a vital role in diagnosing diseases, demand for new MRI contrast agents, with an enhanced sensitivity and advanced functionalities, is very high. During the past decade, various inorganic nanoparticles have been used as MRI contrast agents due to their unique properties, such as large surface area, easy surface functionalization, excellent contrasting effect, and other size-dependent properties. This review provides an overview of recent progress in the development of nanoparticle-based T1-weighted MRI contrast agents. The chemical synthesis of the nanoparticle-based contrast agents and their potential applications were discussed and summarized. In addition, the recent development in nanoparticle-based multimodal contrast agents including T1-weighted MRI/computed X-ray tomography (CT) and T1-weighted MRI/optical were also described, since nanoparticles may curtail the shortcomings of single mode contrast agents in diagnostic and clinical settings by synergistically incorporating functionality.
T1-weighted magnetic resonance; molecular imaging; nanoparticles; contrast agents
Background. Tianma Gouteng Yin (TGY) is widely used for essential hypertension (EH) as adjunctive treatment. Many randomized clinical trials (RCTs) of TGY for EH have been published. However, it has not been evaluated to justify their clinical use and recommendation based on TCM zheng classification. Objectives. To assess the current clinical evidence of TGY as adjunctive treatment for EH with liver yang hyperactivity syndrome (LYHS) and liver-kidney yin deficiency syndrome (LKYDS). Search Strategy. 7 electronic databases were searched until November 20, 2012. Inclusion Criteria. RCTs testing TGY combined with antihypertensive drugs versus antihypertensive drugs were included. Data Extraction and Analyses. Study selection, data extraction, quality assessment, and data analyses were conducted according to the Cochrane standards. Results. 22 RCTs were included. Methodological quality was generally low. Except diuretics treatment group, blood pressure was improved in the other 5 subgroups; zheng was improved in angiotensin converting enzyme inhibitors (ACEIs), calcium channel blockers (CCBs), and “CCB + ACEI” treatment groups. The safety of TGY is still uncertain. Conclusions. No confirmed conclusion about the effectiveness and safety of TGY as adjunctive treatment for EH with LYHS and LKYDS could be made. More rigorous trials are needed to confirm the results.
Arginine (ARG) exerts many beneficial effects on animal body and enhanced angiogenesis, lactogenesis, which finally leads to the improvement in nitrogen (N) metabolism, reproduction, lactation, immunity and growth. Unfortunately, unprotected ARG will be degraded in the rumen and its price is high, thus feeding rumen-protected ARG seems to be uneconomical. Alternatively, N-carbamoyl glutamate (NCG) is structural analogue of N-acetyl glutamate, cofactor of cabamoyl phosphate synthetase1, is lower in rumen degradation compared to ARG. Additionally, rumen epithelial and duodenal cells have potentially utilized the NCG for ureagenesis. Supplementation of NCG to high yielding dairy cows increased plasma concentration of ARG and nitric oxide, decreased the plasma ammonia N and improved lactation performance and N utilization. Supplementation of NCG enhanced pregnancy rates in rats, improved litter size and fetal survival rate, thereby improved the reproductive performance of sows. Oral NCG supplementation increases plasma ARG and somatotropin levels, and increased growth rate and muscle protein synthesis in nursing piglets. The NCG is potential a relatively cheaper source of feed additive to offer vital compensation over oral administration of ARG, resulting in improved ruminant animal health and production. In this article, we reviewed the mechanism of ARG biosynthesis by NCG and their significance in growth, reproduction, milk production and N utilization in ruminant animals.
Arginine; Lactation; N-cabamoyl glutamate; Nitrogen utilization; Pregnancy; Ruminant animals
Objectives. To evaluate the effectiveness and safety of a Ginkgo biloba extract for patients with early diabetic nephropathy. Methods. Randomised controlled trials (RCTs) conducted on adults with early diabetic nephropathy which used Gingko biloba extract were included. The major databases were searched, and manufacturers of Gingko biloba products were contacted for information on any published or unpublished studies. Two authors independently extracted the data from the included studies. Data analysis was conducted using Review Manager 5.0 software. Results. Sixteen RCTs were included. Ginkgo biloba extract decreased the urinary albumin excretion rate (UAER), fasting blood glucose (FBG), serum creatinine (SCR), and blood urea nitrogen (BUN). The extract also improved hemorheology. The methodological quality in the included studies was low. The explicit generation of the allocation sequence was described in only 6 trials. None of the included trials were confirmed to use blinding. Three studies had observed adverse events. One study using angiotensin-converting enzyme inhibitor (ACEi) reported mild cough in both groups. No serious adverse effects were reported. Conclusions. Gingko biloba extract is a valuable drug which has prospect in treating early diabetic nephropathy, especially with high UAER baseline level. The safety for early diabetic nephropathy is uncertain. Long-term, double-blinded RCTs with large sample sizes are still needed to provide stronger evidence.
Stroke is a leading cause of death and disability due to disturbance of blood supply to the brain. As brain is highly sensitive to hypoxia, insufficient oxygen supply is a critical event contributing to ischemic brain injury. Normobaric hyperoxia (NBO) that aims to enhance oxygen delivery to hypoxic tissues has long been considered as a logical neuroprotective therapy for ischemic stroke. To date, many possible mechanisms have been reported to elucidate NBO’s neuroprotection, such as improving tissue oxygenation, increasing cerebral blood flow, reducing oxidative stress and protecting the blood brain barrier. As ischemic stroke triggers a battery of damaging events, combining NBO with other agents or treatments that target multiple mechanisms of injury may achieve better outcome than individual treatment alone. More importantly, time loss is brain loss in acute cerebral ischemia. NBO can be a rapid therapy to attenuate or slow down the evolution of ischemic tissues towards necrosis and therefore “buy time” for reperfusion therapies. This article summarizes the current literatures on NBO as a simple, widely accessible, and potentially cost-effective therapeutic strategy for treatment of acute ischemic stroke.
Oxygen; Ischemia; Oxidative stress; Blood brain barrier; Reperfusion; Blood flow; Neuroprotection
Cyclophilin A (CypA) is the main member of the immunophilin superfamily that has peptidyl-prolyl cis-trans isomerase activity. CypA participates in protein folding, cell signaling, inflammation and tumorigenesis. Further, CypA plays critical roles in the replication of several viruses. Upon influenza virus infection, CypA inhibits viral replication by interacting with the M1 protein. In addition, CypA is incorporated into the influenza virus virions. Finally, Cyclosporin A (CsA), the main inhibitor of CypA, inhibits influenza virus replication through CypA-dependent and -independent pathways. This review briefly summarizes recent advances in understanding the roles of CypA during influenza virus infection.
influenza virus; Cyclophilin A; Cyclosporin A; virus-host interaction
Plants of the genus Elsholtzia (Lamiaceae) have a long history of medicinal use in folk. The phytochemical investigations revealed the presence of flavonoids, phenylpropanoids, terpenoids, and other compounds. Abundant volatile components are also identified. Pure compounds, volatile constituents and crude extracts from the genus exhibited a wide spectrum of in vitro and in vivo pharmacological activities. The aims of this review hopefully provide comprehensive information on the distribution, phytochemistry, volatile components, and pharmacological research of Elsholtzia for exploring the potential and advance researches.
Systemic lupus erythematosus (SLE) is a complex autoimmune disease involving multiple organs. The disease is characterized by the production of pathogenic autoantibodies to DNA and certain nuclear antigens, chronic inflammation, and immune dysregulation. Genetic studies involving SLE patients and mouse models have indicated that multiple lupus susceptible genes contribute to the disease phenotype. Notably, the development of SLE in patients and in certain mouse models exhibits a strong sex bias. In addition, several lines of evidence indicates that activation of interferon-α (IFN-α) signaling in immune cells and alterations in the expression of certain immunomodulatory cytokines contribute to lupus pathogenesis. Studies have implicated factors, such as the X chromosomal gene dosage effect and the sex hormones, in gender bias in SLE. However, the molecular mechanisms remain unclear. Additionally, it remains unclear whether these factors influence the “IFN-signature,” which is associated with SLE. In this regard, a mutually positive regulatory feedback loop between IFNs and estrogen receptor-α (ERα) has been identified in immune cells. Moreover, studies indicate that the expression of certain IFN-inducible p200-family proteins that act as innate immune sensors for cytosolic DNA is differentially regulated by sex hormones. In this review, we discuss how the modulation of the expression of the p200-family proteins in immune cells by sex hormones and IFNs contributes to sex bias in SLE. An improved understanding of the regulation and roles of the p200-family proteins in immune cells is critical to understand lupus pathogenesis as well as response (or the lack of it) to various therapies.
Wavefront aberration affects the quality of retinal image directly. This paper reviews the representation and reconstruction of wavefront aberration, as well as the construction of virtual eye model based on Zernike polynomial coefficients. In addition, the promising prospect of virtual eye model is emphasized.
wavefront aberration; wavefront reconstruction; virtual eye; Zernike polynomial
Nutrition-related health issues have emerged as a major threat to public health since the rebirth of the economy in China starting in the 1980s. To meet this challenge, the Chinese Academy of Sciences established the Institute for Nutritional Sciences (INS) at Shanghai, China ∼8 y ago. The mission of the INS is to apply modern technologies and concepts in nutritional research to understand the molecular mechanism and provide means of intervention in the combat against nutrition-related diseases, including type 2 diabetes, metabolic syndrome, obesity, cardiovascular diseases, and many types of cancers. Through diligent and orchestrated efforts by INS scientists, graduate students, and research staff in the past few years, the INS has become the leading institution in China in the areas of basic nutritional research and metabolic regulation. Scientists at the INS have made important progress in many areas, including the characterization of genetic and nutritional properties of the Chinese population, metabolic control associated with nutrient sensing, molecular mechanisms underlying glucose and lipid metabolism, regulation of metabolism by adipokines and inflammatory pathways, disease intervention using functional foods or extracts of Chinese herbs, and many biological studies related to carcinogenesis. The INS will continue its efforts in understanding the optimal nutritional needs for Chinese people and the molecular causes associated with metabolic diseases, thus paving the way for effective and individualized intervention in the future. This review highlights the major research endeavors undertaken by INS scientists in recent years.
To discover and develop novel natural compounds with therapeutic selectivity or that can preferentially kill cancer cells without significant toxicity to normal cells is an important area in cancer chemotherapy. Kushen, the dried roots of Sophora flavescens Aiton, has a long history of use in traditional Chinese medicine to treat inflammatory diseases and cancer. Kushen alkaloids (KS-As) and kushen flavonoids (KS-Fs) are well-characterized components in kushen. KS-As containing oxymatrine, matrine, and total alkaloids have been developed in China as anticancer drugs. More potent antitumor activities were identified in KS-Fs than in KS-As in vitro and in vivo. KS-Fs may be developed as novel antitumor agents.