Cell metabolism pathways involved in the pathophysiological changes of diabetic peripheral neuropathy

Diabetic peripheral neuropathy is a common complication of diabetes mellitus.Elucidating the pathophysiological metabolic mechanism impels the generation of ideal therapies.However,existing limited treatments for diabetic peripheral neuropathy expose the urgent need for cell metabolism research.Given the lack of comprehensive understanding of energy metabolism changes and related signaling pathways in diabetic peripheral neuropathy,it is essential to explore energy changes and metabolic changes in diabetic peripheral neuropathy to develop suitable treatment methods.This review summarizes the pathophysiological mechanism of diabetic peripheral neuropathy from the perspective of cellular metabolism and the specific interventions for different metabolic pathways to develop effective treatment methods.Various metabolic mechanisms(e.g.,polyol,hexosamine,protein kinase C pathway)are associated with diabetic peripheral neuropathy,and researchers are looking for more effective treatments through these pathways.

A 640×640 ISFET array for detecting cell metabolism

Ion sensitive field effect transistor(ISFET)devices are highly accurate,convenient,fast and low-cost in the detection of ions and biological macromolecules,such as DNA molecules,antibodies,enzymatic substrates and cellular metabolites.For high-throughput cell metabolism detection,we successfully designed a very large-scale biomedical sensing application specific integrated circuit(ASIC)with a 640×640 ISFET array.The circuit design is highly integrated by compressing the size of a pixel to 7.4×7.4μm^(2)and arranging the layout of even and odd columns in an interdigital pattern to maximize the utilization of space.The chip can operate at a speed of 2.083M pixels/s and the dynamic process of the fluid flow on the surface of the array was monitored through ion imaging.The pH sensitivity is 33±4 mV/pH and the drift rate is 0.06 mV/min after 5 h,indicating the stability and robustness of the chip.Moreover,the chip was applied to monitor pH changes in CaSki cells metabolism,with pH shifting from 8.04 to 7.40 on average.This platform has the potential for continuous and parallel monitoring of cell metabolism in single-cell culture arrays.

Metabolic and proteostatic differences in quiescent and active neural stem cells

Adult neural stem cells are neurogenesis progenitor cells that play an important role in neurogenesis.Therefore,neural regeneration may be a promising target for treatment of many neurological illnesses.The regenerative capacity of adult neural stem cells can be chara cterized by two states:quiescent and active.Quiescent adult neural stem cells are more stable and guarantee the quantity and quality of the adult neural stem cell pool.Active adult neural stem cells are chara cterized by rapid proliferation and differentiation into neurons which allow for integration into neural circuits.This review focuses on diffe rences between quiescent and active adult neural stem cells in nutrition metabolism and protein homeostasis.Furthermore,we discuss the physiological significance and underlying advantages of these diffe rences.Due to the limited number of adult neural stem cells studies,we refe rred to studies of embryonic adult neural stem cells or non-mammalian adult neural stem cells to evaluate specific mechanisms.

Development of cell metabolite analysis on microfluidic platform

Cell metabolite analysis is of great interest to analytical chemists and physiologists, with some metabolites having been identified as important indicators of major diseases such as cancer. A highthroughput and sensitive method for drug metabolite analysis will largely promote the drug discovery industry. The basic barrier of metabolite analysis comes from the interference of complex components in cell biological system and low abundance of target substances. As a powerful tool in biosample analysis, microfluidic chip enhances the sensitivity and throughput by integrating multiple functional units into one chip. In this review, we discussed three critical steps of establishing functional microfluidic platform for cellular metabolism study. Cell in vitro culture model, on chip sample pretreatment, and microchip combined detectors were described in details and demonstrated by works in five years. And a brief summary was given to discuss the advantages as well as challenges of applying microchip method in cell metabolite and biosample analysis.

Cardiac stem cells: Current knowledge and future prospects

Regenerative medicine is the field concerned with the repair and restoration of the integrity of damaged human tissues as well as whole organs.Since the inception of the field several decades ago,regenerative medicine therapies,namely stem cells,have received significant attention in preclinical studies and clinical trials.Apart from their known potential for differentiation into the various body cells,stem cells enhance the organ's intrinsic regenerative capacity by altering its environment,whether by exogenous injection or introducing their products that modulate endogenous stem cell function and fate for the sake of regeneration.Recently,research in cardiology has highlighted the evidence for the existence of cardiac stem and progenitor cells(CSCs/CPCs).The global burden of cardiovascular diseases’morbidity and mortality has demanded an in-depth understanding of the biology of CSCs/CPCs aiming at improving the outcome for an innovative therapeutic strategy.This review will discuss the nature of each of the CSCs/CPCs,their environment,their interplay with other cells,and their metabolism.In addition,important issues are tackled concerning the potency of CSCs/CPCs in relation to their secretome for mediating the ability to influence other cells.Moreover,the review will throw the light on the clinical trials and the preclinical studies using CSCs/CPCs and combined therapy for cardiac regeneration.Finally,the novel role of nanotechnology in cardiac regeneration will be explored.

Role of the mechanical microenvironment in cancer development and progression

Cross-talk between tumor cells and mechanical stress in the tumor microenvironment has been shown to be involved in carcinogenesis.High mechanical stress in tumors can alter the metabolism and behaviors of cancer cells and cause cancer cells to attain cancer stem-like cell properties,thus driving tumor progression and promoting metastasis.The mechanical signal is converted into a biochemical signal that activates tumorigenic signaling pathways through mechanotransduction.Herein,we describe the physical changes occurring during reprogramming of cancer cell metabolism,which regulate cancer stem cell functions and promote tumor progression and aggression.Furthermore,we highlight emerging therapeutic strategies targeting mechanotransduction signaling pathways.

Pulsed Vector Magnetic Potential Field Existence

Experimental confirmation discussed the effect of the immediate surroundings of a pulse-powered toroidal coil on biological material which was placed in an environment without the influence of electromagnetic force.

Effects of hydrogen sulfide on storage quality, water mobility and cell wall metabolism of strawberry fruit

The effects of hydrogen sulfide(H_(2)S)on storage quality,cellular water distribution,and cell wall metabolism of strawberry fruit after subjected to shelf or cold storage were investigated.Fruit were fumigated with a range of aqueous NaHS solution(0.4-3.2 mmol/L),then stored at 20℃ for 3 d or 0℃ for 9 d.H_(2)S-treated fruit significantly maintained higher fruit firmness(FF)and titratable acidity(TA)as well as lower decay compared to the control fruit.Furthermore,H_(2)S inhibited the loss in extractable juice(EJ)and improved storage quality that not only resulted from the suppressing of respiration rate,but also from the modification of water mobility and cell wall metabolism.High FF and EJ in H_(2)S-treated fruit were closely associated with lower exchanges of free water between vacuole and cytoplasm/free space or cell wall,water-soluble polysaccharides(WSP),and activities of cell wall-modifying enzymes.Therefore,a potential benefit of H_(2)S on retarding softening was that the H2S can reinforce the hydrogen bonding in polysaccharides and reduce activities of cell wall-modifying enzymes,causing a stabilization of cell wall structure.Although approval of the use of H_(2)S on foods has not yet been granted,an alternative reducing agent gas based on H2S tended to be more effective in improving strawberry quality.

An Electrochemiluminescent Platform for Living Cell Oxygen Metabolism Monitoring

This study has developed a novel sensing platform for the investigation of cell oxygen metabolism.With chitosan@TiO_(2) nanocomposites as supporting matrix which was decorated on the surface of indium tin oxide glass,it can effectively absorb A549 cells and sensitize the electrochemiluminescence(ECL)of luminol.On this platform,the ECL output is dependent on the level of reactive oxygen species(ROSs),which was evidenced by the intervening of resveratrol,a typical ROSs’scavenger.The results indicated that the ECL signal was quenched by the resveratrol within its concentration range from 0.10 nM to 2.97μM.Thus,it is believable that the ECL of luminol sensitively responded upon oxygenic matters on this living cell platform would be powerful for cell oxygen metabolism monitoring.

The role of micro RNAs in hepatocyte metabolism and hepatitis B virus replication

Though efficient vaccines against hepatitis B virus(HBV) and antiviral therapies are available,chronic HBV infection is still a global health problem. The process of HBV infection and HBV life cycle are extensively studied in last decades, however, the mechanisms of HBV-induced alterations of host cell metabolisms and host factors involved in modulating of viral replication are not fully understood. Thus, it is an important issue to examine these specific HBV-host interactions for development of novel strategies for antiviral therapies. Recently, microRNAs(miRNAs), a class of post-transcriptional regulatory small RNA, seem to be the relevant fine tuning factors of various cellular activities and pathways, including cell growth, metabolism, and viral replication. In this review, we summarize the up to date knowledge concerning the virus-host interactions and emphasizing on the role of miRNAs in regulation of HBV replication and host cell metabolism.

Metabolic responses of indigenous bacteria in chicken faeces and maggots to multiple antibiotics via heavy water labeled single-cell Raman spectroscopy

The use of maggots derived from chicken faeces as fish diets might serve as a vehicle for the widespread of multiple antibiotic resistant bacteria(ARB) in the environment. Heavy water labeled single-cell Raman spectroscopy(D_(2)O-Raman) was applied to detect the metabolic responses of indigenous bacteria in chicken faeces and maggots to different concentrations of combined colistin, kanamycin, and vancomycin. By incubating the samples with D_(2)O and antibiotics, metabolically active bacterial cells to antibiotics were distinguished from those inactive by the exhibition of C-D Raman band. Using the C-D band as a universal metabolic biomarker, 96% and 100% of cells in chicken faeces and maggots were revealed to be metabolically active to 1 × minimum inhibition concentration(MIC) of the aforementioned antibiotics. A noticeable decrease in the percentage of active cells from 96% to 76% in faeces and 100% to 93% in maggots was observed at 5 × MIC of antibiotics. However, these ratios were still far above that obtained from the same faeces(1.84%) and maggots(0.51%) samples using a cultivation method, indicating the wide presence of nongrowing but metabolically active bacterial cells under antibiotic treatment. Conclusively, the cultureindependent D_(2)O-Raman approach detected and quantified a large portion of metabolically active indigenous bacteria to multiple antibiotics in their native environments, illustrating the great potential risks of these active cells to spread antibiotic resistance via food chain.

Effects of proteinase A on cultivation and viability characteristics of industrial Saccharomyces cerevisiae WZ65

Proteinase A （PrA）, encoded by PEP4 gene, is a key enzyme in the vacuoles of Saccharomyces cerevisiae. We characterized the effects of PrA on cell growth and glucose metabolism in the industrial S. cerevisiae WZ65. It was observed that the lag phase of cell growth of partial PEP4 gene deletion mutant （36 h） and PrA-negative mutant （48 h） was significantly extended, compared with the wild type strain （24 h） （P〈0.05）, but PrA had no effect on glucose metabolism either under shaking or steady state cultivations. The logistic model was chosen to evaluate the effect of PrA on S. cerevisiae cell growth, and PrA was found to promote cell growth against insufficient oxygen condition in steady state cultivation, but had no effect in shaking cultivation. The effects of glucose starvation on cell growth of partial PEP4 gene deletion strain and PrA-negative mutant were also evaluated. The results show that PrA partial deficiency increased the adaption ofS. cerevisiae to unfavorable nutrient environment, but had no effect on glucose metabolism under the stress of low glucose. During heat shock test, at 60 ℃ the reduced cell viability rate （RCVR） was 10% for the wild type S. cerevisiae and 90% for both mutant strains （P〈0.01）, suggesting that PrA was a negative factor for S. cerevisiae cells to survive under heat shock. As temperatures rose from 60 ℃ to 70℃, the wild type S. cerevisiae had significantly lower relative glucose consumption rate （RGCR） （61.0% and 80.0%） than the partial mutant （78.0% and 98.5%） and the complete mutant （80.0% and 98.0%） （P〈0.05）, suggesting that, in coping with heat shock, cells of the PrA mutants increased their glucose consumption to survive. The present study may provide meaningful information for brewing industry; however, the role of PrA in industrial S. cerevisiae physiology is complex and needs to be further investigated.

Effects of acute or prolonged exposure to leptin on hepatic glucose oxidation

Objective To observe the short-term and long-term effects of leptin on hepatic glucose oxidation and glucokinase gene expression. Methods Rat hepatic cell line BRL was incubated with leptin of different doses (range from 10?ng/ml-200?ng/ml) for 1?h or 24?h. Glucose oxidation was determined by liquid scintillation counting. Glucokinase gene expression (corrected by β-actin) was determined by reverse transcription semi-quantitative polymerase chain reaction. Results Treatment with leptin 10?ng/ml for 1?h had no significant effects on glucose oxidation in hepatic cells. However, at the doses ranging from 50?ng/ml to 200?ng/ml, leptin significantly inhibited glucose oxidation. These effects disappeared when the hepatic cells were exposed to leptin for 24?h. Glucokinase mRNA expression was reduced significantly after both 1?h and 24?h exposure to leptin (100?ng/ml) as compared to that of the control group. Conclusion A low dose of leptin has no significant effect on glucose oxidation in hepatic cells. A relatively high dose of leptin has an acute inhibitory effect on the glucose oxidation in hepatic cells. This effect may likely involve the inhibition of glucokinase gene expression. The inhibitory effect on glucose oxidation is transient and disappears with prolonged exposure time.

Challenges of further studies on gliomas

Gliomas, particularly glioblastomas （GBMs）, are the most common and highly aggressive primary braintumors with poor prognosi-s, in {he past decade, a great many advances have been made in the study on cellular and molecular basis of gliomas. Numerous publications have explored the cell of origin of gliomas, the molecular genetic and epigenetic aberration in gliomas, the molecular classification of GBM subtypes, the possible oncometabolites, the application of targeted therapy for malignant gliomas, etc. However, considering all these findings in recent years, it is clear that a picture of the changes in gliomas is more complex and that it should be characterized further to gain a comprehensive and in-depth understanding of gliomagenesis and for translational application of the new insights into clinical practice, especially in the following important aspects.

Monitoring NAD(H) and NADP(H) dynamics during organismal development with genetically encoded fluorescent biosensors

Cell metabolism plays vital roles in organismal development,but it has been much less studied than transcriptional and epigenetic control of developmental programs.The difficulty might be largely attributed to the lack of in situ metabolite assays.Genetically encoded fluorescent sensors are powerful tools for noninvasive metabolic monitoring in living cells and in vivo by highly spatiotemporal visualization.Among all living organisms,the NAD(H)and NADP(H)pools are essential for maintaining redox homeostasis and for modulating cellular metabolism.Here,we introduce NAD(H)and NADP(H)biosensors,present example assays in developing organisms,and describe promising prospects for how sensors contribute to developmental biology research.

Epigenetic control of autophagy in women’s tumors:role of non-coding RNAs

Cancer remains the second leading cause of death worldwide and a major public health and economic issue.To reduce the burden,new approaches are necessary to diagnose the disease at early stages and improve clinical outcomes of cancer patients,for which understanding the molecular mechanisms of carcinogenesis is crucial.Autophagy is a pro-survival pathway that ensures the removal and renewal of cellular macromolecular structures,thus playing a crucial role in the maintenance of cellular homeostasis.Dysregulation of autophagy can favor chemoresistance and survival of dormant cancer cells,thus favoring cancer progression and relapse.Several studies report dysregulated expression of long non-coding RNAs and micro-RNAs acting as tumor suppressors or tumor promoters by targeting genes involved in the autophagy pathway.Here,we focus on the role played by non-coding RNAs-mediated regulation of autophagy in development and progression of cancers in women.Understanding how epigenetics can impact autophagy might open novel therapeutic strategies in the fight against cancers in women.

The regulation effect of AMPK in immune related diseases

AMP-activated protein kinase (AMPK) is a sensor of cellular energy status that plays a key role in energetic metabolism regulation.Metabolic changes in immune cells, such as dendritic cell (DC), macrophages, neutrophils and lymphocytes that participate in the signal directed programs that promote or inhibit immune mediated diseases, including cancer, atherosclerosis and inflammatory diseases. Multiple pathogenic mechanisms are involved in the initiation and progression of disease, and many pathways have been uncovered. The mechanistic overlap in the metabolic changes and inflammation could indicate that some of the targets they have are in common, whereas AMPK could be useful in treatment of both disorders. The insight into identification of AMPK responsible for specific immune regulation, anti-inflammatory actions and understanding of the underlying molecular mechanism will promote the generation of novel AMPK activators, and provide novel therapy strategy.

Advances in engineering methylotrophic yeast for biosynthesis of valuable chemicals from methanol

Methylotrophic yeasts and bacteria, which can use methanol as carbon and energy source, have beenwildly used as microbial cell factories for biomanufacturing. Due to their robustness in industrial harshconditions, methylotrophic yeasts such as Pichia pastoris have been explored as a cell factory forproduction of proteins and high-value chemicals. Methanol utilization pathway （MUT） is highlyregulated for efficient methanol utilization, and the downstream pathways need extensively constructedand optimized toward target metabolite biosynthesis. Here, we present an overview of methanolmetabolism and regulation in methylotrophic yeasts, among which we focus on the regulation of keygenes involved in methanol metabolism. Besides, the recent progresses in construction and optimizationof downstream biosynthetic pathways for production of high value chemicals, such as polyketides, fattyacids and isoprenoids, are further summarized. Finally, we discuss the current challenges and feasiblestrategies toward constructing efficient methylotrophic cell factories may promote wide applications inthe future.

The influence of metabolic disorders on adaptive immunity

The immune system plays a crucial role in protecting the body from invading pathogens and maintaining tissue homoeostasis.Maintaining homoeostatic lipid metabolism is an important aspect of efficient immune cell function and when disrupted immune cell function is impaired.There are numerous metabolic diseases whereby systemic lipid metabolism and cellular function is impaired.In the context of metabolic disorders,chronic inflammation is suggested to be a major contributor to disease progression.A major contributor to tissue dysfunction in metabolic disease is ectopic lipid deposition,which is generally caused by diet and genetic factors.Thus,we propose the idea,that similar to tissue and organ damage in metabolic disorders,excessive accumulation of lipid in immune cells promotes a dysfunctional immune system(beyond the classical foam cell)and contributes to disease pathology.Herein,we review the evidence that lipid accumulation through diet can modulate the production and function of immune cells by altering cellular lipid content.This can impact immune cell signalling,activation,migration,and death,ultimately affecting key aspects of the immune system such as neutralising pathogens,antigen presentation,effector cell activation and resolving inflammation.