Calcium signaling crosstalk between the endoplasmic reticulum and mitochondria, a new drug development strategies of kidney diseases.

Calcium (Ca2+) acts as a second messenger and constitutes a complex and large information exchange system between the endoplasmic reticulum (ER) and mitochondria; this process is involved in various life activities, such as energy metabolism, cell proliferation and apoptosis. Increasing evidence has suggested that alterations in Ca2+ crosstalk between the ER and mitochondria, including alterations in ER and mitochondrial Ca2+ channels and related Ca2+ regulatory proteins, such as sarco/endoplasmic reticulum Ca2+-ATPase (SERCA), inositol 1,4,5-trisphosphate receptor (IP3R), and calnexin (CNX), are closely associated with the development of kidney disease. Therapies targeting intracellular Ca2+ signaling have emerged as an emerging field in the treatment of renal diseases. In this review, we focused on recent advances in Ca2+ signaling, ER and mitochondrial Ca2+ monitoring methods and Ca2+ homeostasis in the development of renal diseases and sought to identify new targets and insights for the treatment of renal diseases by targeting Ca2+ channels or related Ca2+ regulatory proteins.

Simultaneous Determination of Ibrutinib, Dihydroxydiol Ibrutinib, and Zanubrutinib in Human Plasma by Liquid Chromatography-Mass Spectrometry/Mass Spectrometry.

BACKGROUND: Ibrutinib and zanubrutinib are Bruton tyrosine kinase inhibitors used to treat mantle cell lymphoma, chronic lymphocytic leukemia, and small lymphocytic lymphoma. Dihydroxydiol ibrutinib (DHI) is an active metabolite of the drug. A liquid chromatography-tandem mass spectrometry method was developed to detect ibrutinib, DHI, and zanubrutinib in human plasma. METHODS: The method involved a protein precipitation step, followed by chromatographic separation using a gradient of 10 mM ammonium acetate (containing 0.1% formic acid)-acetonitrile. Ibrutinib-d5 was used as an internal standard. Analytes were separated within 6.5 minutes. The optimized multiple reaction monitoring transitions of m/z 441.1 → 304.2, 475.2 → 304.2, 472.2 → 455.2, and 446.2 → 309.2 were selected to inspect ibrutinib, DHI, zanubrutinib, and the internal standards in positive ion mode. RESULTS: The validated curve ranges included 0.200-800, 0.500-500, and 1.00-1000 ng/mL for ibrutinib, DHI, and zanubrutinib, respectively. The precisions of the lower limit of quantification of samples were below 15.5%, the precisions of the other level samples were below 11.4%, and the accuracies were between -8.6% and 8.4%. The matrix effect and extraction recovery of all compounds ranged between 97.6%-109.0% and 93.9%-105.2%, respectively. The selectivity, accuracy, precision, matrix effect, and extraction recovery results were acceptable according to international method validation guidelines. CONCLUSIONS: A simple and rapid method was developed and validated in this study. This method was used to analyze plasma concentrations of ibrutinib and zanubrutinib in patients with mantle cell lymphoma, chronic lymphocytic leukemia/small lymphocytic lymphoma, or diffuse large B-cell lymphoma. The selected patients were aged between 44 and 74 years.

Effect of the bacterial community assembly process on the microbial remediation of petroleum hydrocarbon-contaminated soil.

Introduction: The accumulation of petroleum hydrocarbons (PHs) in the soil can reduce soil porosity, hinder plant growth, and have a serious negative impact on soil ecology. Previously, we developed PH-degrading bacteria and discovered that the interaction between microorganisms may be more important in the degradation of PHs than the ability of exogenous-degrading bacteria. Nevertheless, the role of microbial ecological processes in the remediation process is frequently overlooked. Methods: This study established six different surfactant-enhanced microbial remediation treatments on PH-contaminated soil using a pot experiment. After 30 days, the PHs removal rate was calculated; the bacterial community assembly process was also determined using the R language program, and the assembly process and the PHs removal rate were correlated. Results and discussion: The rhamnolipid-enhanced Bacillus methylotrophicus remediation achieved the highest PHs removal rate, and the bacterial community assembly process was impacted by deterministic factors, whereas the bacterial community assembly process in other treatments with low removal rates was affected by stochastic factors. When compared to the stochastic assembly process and the PHs removal rate, the deterministic assembly process and the PHs removal rate were found to have a significant positive correlation, indicating that the deterministic assembly process of bacterial communities may mediate the efficient removal of PHs. Therefore, this study recommends that when using microorganisms to remediate contaminated soil, care should be taken to avoid strong soil disturbance because directional regulation of bacterial ecological functions can also contribute to efficient removal of pollutants.

Daytime Radiative Cooling Coating Based on the Y2O3/TiO2 Microparticle-Embedded PDMS Polymer on Energy-Saving Buildings.

Daytime radiative cooling technology can release heat into outer space without consuming any electricity during the day while reflecting as much solar radiation as possible. This characteristic gives radiative cooling materials considerable application potential in the fields of energy-saving buildings, fabrics, and photovoltaic cells. The radiative cooling coating (RC coating) applied to a building should cover a large area of the building surface, so a RC coating was prepared by spraying. The RC coating consisted of highly near-infrared reflective yttrium oxide (Y2O3), titanium dioxide (TiO2), and polydimethylsiloxane (PDMS). The RC coating could reach a high solar reflectance of 92.2% and a high atmospheric window emissivity of 94.9%. The complementary reflectivity of TiO2 and Y2O3 was the key to obtaining high reflectivity for RC coatings. The results of field tests showed that the cavity where the RC coating is cooled was 7.7 °C lower than the ambient temperature under direct sunlight. Moreover, the average radiative cooling power of the RC coating was 72.5 W/m2 on a hot summer day. In addition, the RC coating has good stability and thus can be used in various conditions, such as on outdoor buildings.

Effects of Salicylic Acid Concentration and Post-Treatment Time on the Direct and Systemic Chemical Defense Responses in Maize (Zea mays L.) Following Exogenous Foliar Application.

Salicylic acid (SA) plays a critical role in allergic reactions of plants to pathogens and acquired systemic resistance. Thus far, although some research has been conducted on the direct effects of different concentrations of SA on the chemical defense response of treated plant parts (leaves) after at multiple post-treatments times, few research has reported on the systematic effects of non-treated parts (roots). Therefore, we examined direct and systemic effects of SA concentration and time following foliar application on chemical defense responses in maize variety 5422 with two fully expanded leaves. In the experiments, maize leaves were treated with different SA concentrations of 0.1, 0.5, 1.0, 2.5, 5.0 mM, and then, the presence of defense chemicals and enzymes in treated leaves and non-treated roots was measured at different time points of 3, 12, 24, 48, 72 h following SA foliar application. The results showed that direct and systemic effects of SA treatment to the leaf on chemical defense responses were related to SA concentration and time of measurement after spraying SA. In treated leaves, total phenolics content increased directly by 28.65% at the time point of 12 h following foliar application of 0.5 mM SA. DIMBOA (2,4-dihydroxy-7-methoxy-2H, 1, 4-benzoxazin-3 (4H)-one) content was directly enhanced by 80.56~551.05% after 3~72 h following 0.5~5.0 mM SA treatments. Polyphenol oxidase and superoxide dismutase activities were directly enhanced after 12~72 h following 0.5~5.0 mM SA treatments, whereas peroxidase and catalase activities were increased after 3~24 h following application of 1.0~5.0 mM SA. In non-treated roots, DIMBOA content and polyphenol oxidase activity were enhanced systematically after 3~48 h following 1.0~5.0 mM SA foliar treatments. Superoxide dismutase activities were enhanced after 3~24 h following 0.5~2.5 mM SA applications, but total phenolics content, peroxidase and catalase activity decreased in some particular concentrations or at the different times of measurement in the SA treatment. It can be concluded that SA foliar application at 1.0 and 2.5 mM produces strong chemical defense responses in maize, with the optimal induction time being 24 h following the foliar application.

The Expression of Aroma Components and Related Genes in Merlot and Marselan Scion-Rootstock Grape and Wine.

Rootstocks were bred and selected from several species in order to enhance the resistance against biotic or abiotic stresses. There are few studies on the effect of rootstocks on aroma and related gene expression. This study focused on the effects of three rootstocks, Kober 5BB (5BB), 1103 Paulsen (1103P), and Selection Oppenheim (SO4), on the aroma and volatile-related gene expression levels of Merlot and Marselan berries and wines. These three rootstocks reduced the total aroma content of Merlot wine. 5BB upregulated VvLoXA and showed increased C6 alcohols. 1103P enhanced the linalool from Merlot berry, with marked upregulation of VvLinNer1. Conversely, rootstocks increased the total aroma content of Marselan berry, verified by the related expression levels of volatile-related genes. For Marselan berry, 5BB and 1103P upregulated five VvGTs and nine genes from the LOX and MEP pathway. 1103P increased the contents of C6 alcohols, C6 aldehydes, and citronellol from Marselan berry. Compared to 5BB and SO4, rootstock 1103P provided berries of better quality and richer aroma volatiles to Merlot and Marselan, while all three of the rootstocks had a significant effect on scion-rootstocks.

Effects of Exogenous Salicylic Acid Application to Aboveground Part on the Defense Responses in Bt (Bacillus thuringiensis) and Non-Bt Corn (Zea mays L.) Seedlings.

Bt (Bacillus thuringiensis) corn is one of the top three large-scale commercialized anti-insect transgenic crops around the world. In the present study, we tested the Bt protein content, defense chemicals contents, and defense enzyme activities in both the leaves and roots of Bt corn varieties 5422Bt1 and 5422CBCL, as well as their conventional corn 5422 seedlings, with two fully expanded leaves which had been treated with 2.5 mM exogenous salicylic acid (SA) to the aboveground part for 24 h. The result showed that the SA treatment to the aboveground part could significantly increase the polyphenol oxidase activity of conventional corn 5422, the Bt protein content, and peroxidase activities of Bt corn 5422Bt1, as well as the polyphenol oxidase and peroxidase activity of Bt corn 5422CBCL in the leaves. In the roots, the polyphenol oxidase and peroxidase activity of conventional corn 5422, the polyphenol oxidase and superoxide dismutase activities of Bt corn 5422Bt1, the DIMBOA (2,4-dihydroxy-7-methoxy-2H, 1, 4-benzoxazin-3 (4H)-one) content, and four defense enzymes activities of Bt corn 5422CBCL were systematically increased. These findings suggest that the direct effect of SA application to aboveground part on the leaf defense responses in Bt corn 5422CBCL is stronger than that in non-Bt corn. Meanwhile, the systemic effect of SA on the root defense responses in Bt corn 5422CBCL is stronger than that in conventional corn 5422 and Bt corn 5422Bt1. It can be concluded that the Bt gene introduction and endogenous chemical defense responses of corns act synergistically during the SA-induced defense processes to the aboveground part. Different transformation events affected the root defense response when the SA treatment was applied to the aboveground part.

The Different Classification of Hospitals Impact on Medical Outcomes of Patients in China.

Background: In China, different classification of hospitals (COH) provide treatment for patients with different degrees of illness. COH play an important role in Chinese medical outcomes, but there is a lack of quantitative description of how much impact the results have. The objective of this study is to examine the correlation between COH on medical outcomes with the hope of providing insights into appropriate care and resource allocation. Methods: From the perspective of the COH framework, using the Urban Employee Basic Medical Insurance (UEBMI) data of Chengdu City from 2011 to 2015, with a sample size of 512,658 hospitalized patients, this study used the nested multinomial logit model (NMNL) to estimate the impact of COH on the medical outcomes. Results: The patients were mainly elderly, with an average age of 66.28 years old. The average length of stay was 9.61 days. The female and male gender were split evenly. A high level of hospitals is positively and significantly associated with the death and transfer rates (p < 0.001), which may be related to more severe illness among patients in high COH. Conclusion: The COH made a difference in the medical outcomes significantly. COH should be reasonably selected according to disease types to achieve the optimal medical outcome. So, China should promote the construction of a tiered delivery system.

Circular RNA_0120376 regulates microRNA-148b-3 and centrosomal protein 55 to promote non-small cell lung cancer development.

Circular RNAs (circRNAs) are non-coding RNAs with covalent closed-loop structures that are vital in regulating diverse pathological processes. This work is aimed to investigate the role of circ_0120376 in non-small cell lung cancer (NSCLC). Circ_0120376, microRNA (miR)-148b-3p, and centrosomal protein 55 (CEP55) mRNA expression in NSCLC tissues and cells were determined using qRT-PCR. The influences of circ_0120376 and miR-148b-3p on the proliferation of NSCLC cell lines were analyzed by CCK-8 and colony formation assays. Apoptosis was analyzed by flow cytometry. Cell migration and invasion were analyzed using the Transwell experiment. Binding relationships between circ_0120376 and miR-148b-3p and between miR-148b-3p and CEP55 3'UTR were investigated using the dual-luciferase reporter experiment and the RIP experiment. Western blot was conducted to analyze the regulatory effect of circ_0120376 and miR-148b-3p on CEP55 expression. We found that circ_0120376 was markedly overexpressed in NSCLC, and its overexpression was positively associated with increased T stage and lymph node metastasis of the patients. Functional experiments unveiled that circ_0120376 enhanced the proliferation, migration and invasion of NSCLC cells and impeded apoptosis, while knocking down circ_0120376 remarkably suppressed the malignant features of NSCLC cells mentioned above. Circ_0120376 could adsorb miR-148b-3p to reduce miR-148b-3p expression, and circ_0120376 could increase CEP55 expression via adsorbing miR-148b-3p. In summary, circ_0120376 contributes to the malignancy of NSCLC cells through a ceRNA mechanism via regulating miR-148b-3p/CEP55 axis. Circ_0120376 is likely to be a potential diagnostic biomarker and therapeutic target for NSCLC.

Pyroptosis, metabolism, and tumor immune microenvironment.

In response to a wide range of stimulations, host cells activate pyroptosis, a kind of inflammatory cell death which is provoked by the cytosolic sensing of danger signals and pathogen infection. In manipulating the cleavage of gasdermins (GSDMs), researchers have found that GSDM proteins serve as the real executors and the deterministic players in fate decisions of pyroptotic cells. Whether inflammatory characteristics induced by pyroptosis could cause damage the host or improve immune activity is largely dependent on the context, timing, and response degree. Here, we systematically review current points involved in regulatory mechanisms and the multidimensional roles of pyroptosis in several metabolic diseases and the tumor microenvironment. Targeting pyroptosis may reveal potential therapeutic avenues.

Circ_0001806 Promotes the Proliferation, Migration and Invasion of NSCLC Cells Through miR-1182/NOVA2 Axis.

BACKGROUND: Circular RNAs (circRNAs) are non-coding RNAs with a covalently closed loop. circRNAs affect the progression of diverse cancers. Nonetheless, circ_0001806 expression and function in non-small cell lung cancer (NSCLC) are undefined. METHODS: qRT-PCR was executed to examine circ_0001806, miR-1182 and NOVA2 mRNA expression levels in NSCLC tissues and cells. CCK-8, EdU, cell scratch test and Transwell assay were conducted to examine the viability, multiplication, migration and invasion of NSCLC cell lines H1650 and HCC827. The binding sites between circ_0001806 and miR-1182, miR-1182 and NOVA2 mRNA were predicted by the circular RNA Interactome and TargetScan databases, and the dual-luciferase reporter gene experiment was employed for verification. Western blot was implemented to examine NOVA2 expression. RESULTS: Circ_0001806 expression in NSCLC tissues and cell lines was substantially augmented, while miR-1182 expression was markedly decreased. Circ_0001806 facilitated the multiplication, migration and invasion of H1650 and HCC827 cells, while miR-1182 exerted the opposite effect. Circ_0001806 indirectly enhanced NOVA2 expression by specifically down-modulating miR-1182. CONCLUSION: Circ_0001806 augments NOVA2 expression by targeting miR-1182 to enhance the multiplication, migration and invasion of NSCLC cells.

Long Non-coding RNA LINC02474 Affects Metastasis and Apoptosis of Colorectal Cancer by Inhibiting the Expression of GZMB.

BACKGROUND: Colorectal cancer (CRC) is one of the most frequently diagnosed malignancies. Metastasis is the main event that impedes the therapeutic effect on CRC, and its underlying mechanisms remain largely unclear. LINC02474 is a novel long noncoding RNA (lncRNA) associated with metastasis of CRC, while little is known about how LINC02474 regulates these malignant characteristics. METHODS: Expressions of LINC02474 and granzyme B (GZMB) were assessed by quantitative real-time polymerase chain reaction (qRT-PCR) or Western blotting analysis. Cell metastasis was detected by transwell assay and metastatic nude mouse model, and apoptosis was determined by Western blotting analysis and flow cytometry. Besides, the interaction between LINC02474 and GZMB was detected by dual-luciferase reporter assays. RESULTS: The expression of LINC02474 was significantly up-regulated in CRC tissues. Moreover, depletion of LINC02474 damaged the metastatic abilities of CRC cells in vivo and in vitro while boosting apoptosis. Besides, up-regulation of LINC02474 could promote migration and invasion, while apoptosis was inhibited in CRC cells. Besides, down-regulation of LINC02474 promoted the expression of GZMB, and interference of GZMB could increase the metastatic abilities of CRC cells while reducing apoptosis. Furthermore, LINC02474 was related to the transcriptional repression of GZMB in CRC cells determined by the dual-luciferase reporter assay. CONCLUSIONS: The findings revealed that a novel lncRNA, LINC02474, as an oncogene, could promote metastasis, but limit apoptosis partly by impeding GZMB expression in CRC. Besides, LINC02474 had the potential to be used as a biomarker in the prognosis of CRC.

Progress of exosomes in the diagnosis and treatment of lung cancer.

The incidence and mortality of lung cancer account for first place all over the world. Lung cancer lacks early diagnostic biomarkers; lung cancer patients are usually diagnosed in both middle and advanced stages and have poor treatment outcomes. It is more important to find the first diagnostic tools for lung cancer with high specificity and sensitivity. Besides, exosomes are usually nanometer-sized bi-layered lipid vesicles formed and produced by various types of cells. As one of the main modes of intercellular communication, they can deliver multiple functional biomolecules, such as DNA, microRNAs, messenger RNA (mRNA), long non-coding RNA, and proteins, and the events as mentioned above affects different physiological processes of recipient cells. It has been reported that exosomes are involved in different types of cancer, including lung cancer. Various studies proved that exosomes are involved in multiple cancer processes such as cell proliferation, metastasis, epithelial-mesenchymal transition (EMT), angiogenesis, and the tumor microenvironment in lung cancer. Tumor-derived exosomes (TEX) contain a variety of stimulatory and inhibitory factors involved in regulating immune response, which can affect the tumor microenvironment (TME) and thus participate in the formation and progression of lung cancer. This review's primary purpose to review the latest research progress of exosomes in diagnosing and treating lung cancer.

The Impact of Air Pollution on Healthcare Expenditure for Respiratory Diseases: Evidence from the People's Republic of China.

BACKGROUND: Air pollution is an important factor in health outcomes and health-care expenditure. It has become an important issue of global concern. The objective of this study was to explore the influence of air pollution on the economic burden of respiratory diseases using different levels of PM2.5. METHODS: Starting from the demand side, we took the 3,546 patients in the Respiratory and Critical Care Department of a tertiary hospital in Beijing between 2013 and 2015 as examples, combining daily air-quality data using a generalized linear regression-analysis model to explore the impact of air pollution on health-care expenditure on a microindividual level. RESULTS: We found that PM2.5 had a significant impact on health-care expenditure on respiratory diseases. It had a positive impact on total health-care expenditure, drug expenditure, and antibiotic expenditure. The impact of different levels of air pollution on the health care-expenditure burden of disease was heterogeneous. As the air-pollution index increased, health care-expenditure burden of respiratory diseases also gradually raised. The impact of PM10 and air-quality index had a positive impact on health-care expenditure for respiratory diseases. Air pollution had a significant impact on health care-expenditure burden of respiratory diseases. The effect of length of stay on various health-care expenditure was significantly positive. CONCLUSION: The impact of mortality-risk classification on various health-care expenditure is significant. Therefore, policy-making must take into account both the supply side and the demand side of health-care services. Furthermore, the government should strengthen environmental governance, pay attention to the heterogeneity of the health care-expenditure burden affected by environmental pollution, improve the medical insurance system, and improve the health of residents to reduce the health care-expenditure burden.

The Effect of Population Aging on Healthcare Expenditure from a Healthcare Demand Perspective Among Different Age Groups: Evidence from Beijing City in the People's Republic of China.

BACKGROUND: With population aging (PA), the healthcare expenditure (HE) increases. The aim of this study is to analyze the HE of different age groups and the effect of age on HE among different age groups. METHODS: Combining PA and HE data, this study used the fixed effect model and parameter estimation method to evaluate the influence of different age groups on HE from 2008 to 2014. RESULTS: The age effect of HE for the population aged 65 or over was the most significant among the different age groups. Based on PA and HE data, HE per capita of the age group 65 years or over is 7.25 times as much as the population aged < 25 years, 1.61 times as much as the population aged 25~59 years, and 3.47 times as much as the population aged 60~64 years. Based on the result of the fixed effect model, HE per capita of the age group <25 years was 218.39 Yuan (CNY) (USD $31.2). HE per capita of the age group 25~59 years old increased to 1,548.62 Yuan (CNY) (USD $221.2). HE per capita of the 60~64 years age group will be 921.56 Yuan (CNY) (USD $131.7), 4.22 times as much as that of the age group < 25 years. HE per capita in the age group of 65 years or over is 2,538.88 Yuan (CNY) (USD $362.7), 11.63 times as much as that of the age group <25 years. CONCLUSION: The results suggest that PA in China is intensifying. In order to control the rising of HE, the government should not only address the supply side such as reforming medical insurance payment, developing new technologies, but also focusing on solving the demand side such as improving the quality of healthcare services, solving environmental pollution, and improving the residents' health.

The effect of different classification of hospitals on medical expenditure from perspective of classification of hospitals framework: evidence from China.

BACKGROUND: Different classification of hospitals (COH) have an important impact on medical expenditures in China. The objective of this study is to examine the impact of COH on medical expenditures with the hope of providing insights into appropriate care and resource allocation. METHODS: From the perspective of COH framework, using the Urban Employee Basic Medical Insurance (UEBMI) data of Chengdu City from 2011 to 2015, with sample size of 488,623 hospitalized patients, our study empirically analyzed the effect of COH on medical expenditure by multivariate regression modeling. RESULTS: The average medical expenditure was 5468.86 Yuan (CNY), the average expenditure of drug, diagnostic testing, medical consumables, nursing care, bed, surgery and blood expenditures were 1980.06 Yuan (CNY), 1536.27 Yuan (CNY), 500.01 Yuan (CNY), 166.23 Yuan (CNY), 221.98 Yuan (CNY), 983.18 Yuan (CNY) and 1733.21 Yuan (CNY) respectively. Patients included in the analysis were mainly elderly, with an average age of 86.65 years old. Female and male gender were split evenly. The influence of COH on total medical expenditures was significantly negative (p < 0.001). The reimbursement ratio of UEBMI had a significantly positive (p < 0.001) effect on various types of medical expenditures, indicating that the higher the reimbursement ratio was, the higher the medical expenditures would be. CONCLUSIONS: COH influenced medical expenditures significantly. In consideration of reducing medical expenditures, the government should not only start from the supply side of healthcare services, but also focus on addressing the demand side.

LncRNA MIR503HG Inhibits Non-Small Cell Lung Cancer Cell Proliferation by Inducing Cell Cycle Arrest Through the Downregulation of Cyclin D1.

INTRODUCTION: LncRNA MIR503HG has been reported to participate in liver cancer and ALK-negative anaplastic large-cell lymphoma, while its role in non-small cell lung cancer (NSCLC) is unknown. We therefore investigated the functions of lncRNA MIR503HG in NSCLC. METHODS: MIR503HG expression in paired cancer and non-cancer tissues from NSCLC patients was analyzed by RT-qPCR. The interaction between cyclin D1 and MIR503HG was analyzed by overexpression experiments. Cell cycle analysis was performed by flow cytometry. Cell proliferation was analyzed by CCK-8 assay. RESULTS: MIR503HG was downregulated in NSCLC and low levels of MIR503HG were associated with poor survival. In contrast, cyclin D1 was upregulated in NSCLC, and cyclin D1 and MIR503HG were inversely correlated. In NSCLC cells, overexpression experiments revealed that MIR503HG functioned as an upstream inhibitor of cyclin D1. MIR503HG overexpression led to G1 cell cycle arrest, while overexpression of cyclin D1 attenuated the effects of MIR503HG overexpression. Similarly, MIR503HG overexpression resulted in reduced cell proliferation rate, while overexpression of cyclin D1 caused the increased cell proliferation rate and attenuated effects of MIR503HG overexpression. CONCLUSION: MIR503HG inhibits NSCLC cell proliferation by inducing cell cycle arrest through the downregulation of cyclin D1.

The Potential Roles of Exosomes in Chronic Obstructive Pulmonary Disease.

Currently, chronic obstructive pulmonary disease (COPD) is one of the most common chronic lung diseases. Chronic obstructive pulmonary disease is characterized by progressive loss of lung function due to chronic inflammatory responses in the lungs caused by repeated exposure to harmful environmental stimuli. Chronic obstructive pulmonary disease is a persistent disease, with an estimated 384 million people worldwide living with COPD. It is listed as the third leading cause of death. Exosomes contain various components, such as lipids, microRNAs (miRNAs), long non-coding RNAs(lncRNAs), and proteins. They are essential mediators of intercellular communication and can regulate the biological properties of target cells. With the deepening of exosome research, it is found that exosomes are strictly related to the occurrence and development of COPD. Therefore, this review aims to highlight the unique role of immune-cell-derived exosomes in disease through complex interactions and their potentials as potential biomarkers new types of COPD.

Long noncoding RNA LINC02418 regulates MELK expression by acting as a ceRNA and may serve as a diagnostic marker for colorectal cancer.

Some types of long noncoding RNAs (lncRNAs) are aberrantly expressed in human diseases, including cancer. However, the overall biological roles and clinical significances of most lncRNAs in colorectal cancer (CRC) are not fully understood. First, The Cancer Genome Atlas (TCGA) was analyzed to identify differentially expressed lncRNAs between CRC tissues and noncancerous tissues. We identified that LINC02418 was highly expressed in CRC tissues and cell lines. Next, we evaluated the effect of LINC02418 on CRC tumorigenesis and its regulatory functions of absorbing microRNA and indirectly stimulating protein expression by acting as a ceRNA. Mechanistically, LINC02418 acted as a ceRNA to upregulate MELK expression by absorbing miR-1273g-3p. In addition, the diagnostic performance of cell-free LINC02418 and exosomal LINC02418 were both evaluated by the receiver operating characteristic curve and the area under the curve (AUC). Exosomal LINC02418 could distinguish the patients with CRC from the healthy controls (AUC = 0.8978, 95% confidence interval = 0.8644-0.9351) better than cell-free LINC02418 (AUC = 0.6784, 95% confidence interval = 0.6116-0.7452). Collectively, we determined that LINC02418 was significantly overexpressed in CRC and that the LINC02418-miR-1273g-3p-MELK axis played a critical role in CRC tumorigenesis. Finally, exosomal LINC02418 is a promising, novel biomarker that can be used for the clinical diagnosis of CRC.