ABSTRACT
Cytoplasmic dynein participates in transport functions and is essential in spermatogenesis. KM23 belongs to the dynein light chain family. The TGFß signaling pathway is indispensable in spermatogenesis, and Smad2 is an important member of this pathway. We cloned PTKM23 and PTSMAD2 from Portunus trituberculatus and measured their expression during spermatogenesis. PTKM23 may be related to cell division, acrosome formation and nuclear remodeling, and PTSMAD2 may participate in regulating the expression of genes related to spermatogenesis. We assessed the localization of PTKM23 with PTDHC and α-Tubulin, and the results suggested that PTKM23 functions in intracellular transport during spermatogenesis. We knocked down PTKM23 in vivo, and the expression of p53, B-CATAENIN and CYCLIN B decreased significantly, further suggesting a role of PTKM23 in transport and cell division. The localization of PTDIC with α-Tubulin and that of PTSMAD2 with PTDHC changed after PTKM23 knockdown. We transfected PTKM23 and PTSMAD2 into HEK-293 T cells and verified their colocalization. These results indicate that PTKM23 is involved in the assembly of cytoplasmic dynein and microtubules during spermatogenesis and that PTKM23 mediates the participation of cytoplasmic dynein in the transport of PTSMAD2 during spermatogenesis. This study provides a theoretical molecular biological basis for the breeding of P. trituberculatus.
ABSTRACT
Current treatments for patients in the active phase of Crohn's disease (CD) include conventional treatments and biological treatments. Infliximab (IFX), a TNF-α antagonist, is recommended to induce remission in patients with moderate-to-severe CD who have not responded to conventional therapy. IFX terminates the inflammatory cascade by inhibiting the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and caspase signaling pathways and increases the apoptosis of activated T cells in inflamed tissues.
Subject(s)
Atrioventricular Block , Crohn Disease , Humans , Infliximab/adverse effects , Crohn Disease/chemically induced , Antibodies, Monoclonal/therapeutic use , Atrioventricular Block/chemically induced , Tumor Necrosis Factor-alpha , Gastrointestinal Agents/adverse effects , Treatment OutcomeABSTRACT
Current treatments for patients in the active phase of Crohn's disease (CD) include conventional treatments and biological treatments. Infliximab (IFX), a TNF-α antagonist, is recommended to induce remission in patients with moderate-to-severe CD who have not responded to conventional therapy. IFX terminates the inflammatory cascade by inhibiting the nuclear factor-κB (NF-κB), mitogen-activated protein kinase (MAPK), and caspase signaling pathways and increases the apoptosis of activated T cells in inflamed tissues. (AU)
Subject(s)
Humans , Male , Adolescent , Crohn Disease/complications , Hyperlipoproteinemia Type II/complications , Atrioventricular Block , Infliximab , Arrhythmias, CardiacABSTRACT
Puerarin, a class of isoflavonoid compounds concentrated in the roots of Puerarias, has antipyretic, sedative, and coronary blood-flow-increasing properties. Although the biosynthetic pathways of puerarin have been investigated by previous researchers, studies focusing on the influence of different growth stages on the accumulation of metabolites in the puerarin pathway are not detailed, and it is still controversial at the last step of the 8-C-glycosylation reaction. In this study, we conducted a comprehensive analysis of the metabolomic and transcriptomic changes in Pueraria montana var. thomsonii during two growing years, focusing on the vigorous growth and dormant stages, to elucidate the underlying mechanisms governing the changes in metabolite and gene expression within the puerarin biosynthesis pathway. In a comparison of the two growth stages in the two groups, puerarin and daidzin, the main downstream metabolites in the puerarin biosynthesis pathway, were found to accumulate mainly during the vigorous growth stage. We also identified 67 common differentially expressed genes in this pathway based on gene expression differences at different growth stages. Furthermore, we identified four candidate 8-C-GT genes that potentially contribute to the conversion of daidzein into puerarin and eight candidate 7-O-GT genes that may be involved in the conversion of daidzein into daidzin. A co-expression network analysis of important UGTs and HIDs along with daidzein and puerarin was conducted. Overall, our study contributes to the knowledge of puerarin biosynthesis and offers information about the stage at which the 8-C-glycosylation reaction occurs in biosynthesis. These findings provide valuable insights into the cultivation and quality enhancement of Pueraria montana var. thomsonii.
Subject(s)
Pueraria , Pueraria/genetics , Pueraria/metabolism , Gene Expression Profiling , Transcriptome , MetabolomicsABSTRACT
Coptis chinensis is a perennial herb of the Ranunculaceae family. The isoquinoline alkaloid is the main active component of C. chinensis, mainly exists in its rhizomes and has high clinical application potential. The in vitro synthesis of isoquinoline alkaloids is difficult because their structures are complex; hence, plants are still the main source of them. In this study, two-year and four-year rhizomes of C. chinensis were selected to investigate the effect of growth years on the accumulation of isoquinoline alkaloids. Two-year and four-year C. chinensis were selected for metabolomics detection and transcriptomic analysis. A total of 413 alkaloids were detected by metabolomics analysis, of which 92 were isoquinoline alkaloids. (S)-reticuline was a significantly different accumulated metabolite of the isoquinoline alkaloids biosynthetic pathway in C. chinensis between the two groups. The results of transcriptome analysis showed that a total of 464 differential genes were identified, 36 of which were associated with the isoquinoline alkaloid biosynthesis pathway of C. chinensis. Among them, 18 genes were correlated with the content of important isoquinoline alkaloids. Overall, this study provided a comprehensive metabolomic and transcriptomic analysis of the rapid growth stage of C. chinensis rhizome from the perspective of growth years. It brought new insights into the biosynthetic pathway of isoquinoline alkaloids and provided information for utilizing biotechnology to improve their contents in C. chinensis.
Subject(s)
Alkaloids , Coptis , Coptis chinensis , Transcriptome , Coptis/genetics , Coptis/chemistry , Coptis/metabolism , Alkaloids/genetics , Alkaloids/metabolism , Metabolome , Isoquinolines/metabolismABSTRACT
Mammalian target of rapamycin (mTOR) controls cellular anabolism, and mTOR signaling is hyperactive in most cancer cells. As a result, inhibition of mTOR signaling benefits cancer patients. Rapamycin is a US Food and Drug Administration (FDA)-approved drug, a specific mTOR complex 1 (mTORC1) inhibitor, for the treatment of several different types of cancer. However, rapamycin is reported to inhibit cancer growth rather than induce apoptosis. Pyruvate dehydrogenase complex (PDHc) is the gatekeeper for mitochondrial pyruvate oxidation. PDHc inactivation has been observed in a number of cancer cells, and this alteration protects cancer cells from senescence and nicotinamide adenine dinucleotide (NAD+|) exhaustion. In this paper, we describe our finding that rapamycin treatment promotes pyruvate dehydrogenase E1 subunit alpha 1 (PDHA1) phosphorylation and leads to PDHc inactivation dependent on mTOR signaling inhibition in cells. This inactivation reduces the sensitivity of cancer cells' response to rapamycin. As a result, rebooting PDHc activity with dichloroacetic acid (DCA), a pyruvate dehydrogenase kinase (PDK) inhibitor, promotes cancer cells' susceptibility to rapamycin treatment in vitro and in vivo.
Subject(s)
Neoplasms , Sirolimus , Humans , Sirolimus/pharmacology , Dichloroacetic Acid/pharmacology , Pyruvate Dehydrogenase Complex , TOR Serine-Threonine Kinases , Mechanistic Target of Rapamycin Complex 1 , Neoplasms/drug therapyABSTRACT
The rapid development of multi-satellite formations requires inter-satellite radio frequency (RF) measurement to be both precise and scalable. The navigation estimation of multi-satellite formations using a unified time reference demands the simultaneous RF measurement of the inter-satellite range and time difference. However, high-precision inter-satellite RF ranging and time difference measurements are investigated separately in existing studies. Different from the conventional two-way ranging (TWR) method, which is limited by its reliance on a high-performance atomic clock and navigation ephemeris, asymmetric double-sided two-way ranging (ADS-TWR)-based inter-satellite measurement schemes can eliminate such reliance while ensuring measurement precision and scalability. However, ADS-TWR was originally proposed for ranging-only applications. In this study, by fully exploiting the time-division non-coherent measurement characteristic of ADS-TWR, a joint RF measurement method is proposed to obtain the inter-satellite range and time difference simultaneously. Moreover, a multi-satellite clock synchronization scheme is proposed based on the joint measurement method. The experimental results show that when inter-satellite ranges are hundreds of kilometers, the joint measurement system has a centimeter-level accuracy for ranging and a hundred-picosecond-level accuracy for time difference measurement, and the maximum clock synchronization error was only about 1 ns.
ABSTRACT
BACKGROUND: Endometriosis is a crippling, ongoing, chronic inflammatory condition. The management of these patients has been impacted by the current COVID-19 pandemic, which is still controversial. This study compared the clinical therapy outcomes and psychological scores between before and during- the epidemic. METHOD: The data of patients who were diagnosed with endometriosis in the Department of Gynecology, Chongqing Traditional Chinese Medicine Hospital from January 2018 to December 2022 were collected. The patients were divided into pre- and intra-COVID groups. The treatment results and psychological status of the two groups were compared. RESULTS: A total of 1022 patients with endometriosis were enrolled, with a mean age of 33.16 ± 9.81 years and a BMI of 23.90 ± 3.04 kg/m2, of which 434 cases (434/1022, 42.5%) were in the pre-COVID group and 588 cases (588/1022, 57.5%) in the intra-COVID group. Both groups were well balanced for age, BMI, history of abdominopelvic surgery, family relationships, education level, and duration between initial diagnosis and admission. Compared to the Pre-COVID group, the intra-COVID group had a higher proportion of patients with chronic pelvic pain (297/434, 68.4% vs. 447/588, 76.0%, p = 0.007) and dysmenorrhea (249/434, 62.8% vs. 402/588, 70.0%, p < 0.001), more patients requiring surgery (93/434, 21.4% vs. 178/588, 30.3%, p = 0.002) and longer hospital stays (5.82 ± 2.24 days vs. 7.71 ± 2.15 days, p < 0.001). A total of 830 questionnaires were completed. In the Intra-COVID group, PHQ-2 (2 (2, 3) vs. 3 (2,4), p < 0.001), GAD-2 (2 (1, 2) vs. 3 (2, 3), p < 0.001), PHQ-4 (4 (3, 5) vs. 5 (4, 7), EHP-5 (20.26 ± 6.05 vs. 28.08 ± 7.95, p < 0.001) scores were higher than that in the pre-COVID group, while BRS (3.0 (2.2, 4.0) vs. 2.4 (1.8, 3.8), p = 0.470) were not significantly different. CONCLUSION: During the COVID-19 epidemic, patients with endometriosis may have reduced visits to the hospital, more severe related symptoms, longer length of hospital stays, and worse quality of life, with the possible cause being a disturbance in hormone levels through increased anxiety and depression. This provides a valid clinical basis for optimizing the management of patients with endometriosis and for early psychological intervention during the epidemic.
Subject(s)
COVID-19 , Endometriosis , Female , Humans , Young Adult , Adult , Endometriosis/complications , Endometriosis/epidemiology , Endometriosis/therapy , Quality of Life , Pandemics , Treatment OutcomeABSTRACT
The mechanisms link obesity and hypertension are not well understood. One possibility is the alterations in adipose-derived adipokines that modulate insulin resistance (IR) and cardiovascular homeostasis. We aimed to assess the associations between hypertension and four adipokine levels in Chinese youth, and to examine to what extent the associations are mediated by IR. We utilized cross-sectional data from the Beijing Children and Adolescents Metabolic Syndrome (BCAMS) Study Cohort (n = 559, mean age = 20.2 years). Plasma leptin, adiponectin, retinol binding protein 4 (RBP4) and fibroblast growth factor 21 (FGF21) levels were assayed. The relationships between adipokines and hypertension and the possible mediation effect of IR were evaluated. Youth with hypertension have lower adiponectin and higher leptin, FGF21 (all P < 0.001) and RBP4 levels (p = 0.06) compared to their counterparts. Moreover, the co-existence of these two or more adipokine abnormalities in youth leads to a 9-fold increased risk for hypertension (OR: 9.19; 95% CI, 4.01-21.08) compared with these without abnormalities. However, in the fully adjusted and BMI-adjusted analyses, only FGF21 was a significant predictor of hypertension (OR: 2.12; 95% CI, 1.34-3.36). Mediation analysis revealed that the associations between leptin, adiponectin, RBP4 and hypertension are totally mediated by IR (proportion: 63.9%, 65.4%, and 31.6%, respectively), while BMI and IR partly mediated the association between FGF21 and hypertension (proportion: 30.6%, 21.2%). Our findings suggest that dysregulation of adipokines might result in hypertension in youth. Leptin, adiponectin and RBP4 may exert their functions in hypertension through adiposity-related IR, whereas FGF21 might be used as an independent marker of hypertension in youth.
Subject(s)
Hypertension , Insulin Resistance , Adolescent , Child , Humans , Young Adult , Adipokines , Adiponectin , Beijing , Cross-Sectional Studies , Leptin , Obesity , Retinol-Binding Proteins, PlasmaABSTRACT
BACKGROUND: Histone acetyltransferases (HATs) play an important role in plant growth and development, stress response, and regulation of secondary metabolite biosynthesis. Hemp (Cannabis sativa L.) is famous for its high industrial, nutritional, and medicinal value. It contains non-psychoactive cannabinoid cannabidiol (CBD) and cannabinol (CBG), which play important roles as anti-inflammatory and anti-anxiety. At present, the involvement of HATs in the regulation of cannabinoid CBD and CBG synthesis has not been clarified. METHODS: The members of HAT genes family in hemp were systematically analyzed by bioinformatics analysis. In addition, the expression level of HATs and the level of histone acetylation modification were analyzed based on transcriptome data and protein modification data. Real-time quantitative PCR was used to verify the changes in gene expression levels after inhibitor treatment. The changes of CBD and CBG contents after inhibitor treatment were verified by HPLC-MS analysis. RESULTS: Here, 11 HAT genes were identified in the hemp genome. Phylogenetic analysis showed that hemp HAT family genes can be divided into six groups. Cannabinoid synthesis genes exhibited spatiotemporal specificity, and histones were acetylated in different inflorescence developmental stages. The expression of cannabinoid synthesis genes was inhibited and the content of CBD and CBG declined by 10% to 55% in the samples treated by HAT inhibitor (PU139). Results indicated that CsHAT genes may regulate cannabinoid synthesis through altering histone acetylation. CONCLUSIONS: Our study provides genetic information of HATs responsible for cannabinoid synthesis, and offers a new approach for increasing the content of cannabinoid in hemp.
ABSTRACT
Cytoplasmic Dynein is a multiple-subunit macromolecular motor protein involved in the transport process of cells. The Dynein intermediate chain (DIC) is one of the subunits of Dynein-1. In our previous studies, we showed that Pt-DIC may play an important role in the nuclear deformation of spermiogenesis in Portunus trituberculatus. Lamin B is essential for maintaining nuclear structure and functions. Surprisingly, Pt-Lamin B was expressed not only in the perinucleus but also in the pro-acrosome during spermiogenesis in P. trituberculatus. Studies have also shown that Dynein-1 can mediate the transport of Lamin B in mammals. Thus, to study the relationship of Pt-DIC and Pt-Lamin B in the spermatogenesis of P. trituberculatus, we knocked down the Pt-DIC gene in P. trituberculatus by RNAi. The results showed that the distribution of Pt-DIC and Pt-Lamin B in spermiogenesis was abnormal, and the colocalization was weakened. Moreover, we verified the interaction of Pt-DIC and Pt-Lamin B via coimmunoprecipitation. Therefore, our results suggested that both Pt-DIC and Pt-Lamin B were involved in the spermatogenesis of P. trituberculatus, and one of the functions of Dynein-1 is to mediate the transport of Lamin B in the spermiogenesis of P. trituberculatus.
Subject(s)
Lamin Type B , Spermatogenesis , Male , Animals , Spermatogenesis/genetics , Acrosome , Cytoplasmic Dyneins , Dyneins/genetics , MammalsABSTRACT
Hemp seeds are rich in metabolites such as protein, lipids and flavonoids, which are beneficial to health and can be used as a nutritional supplement. Few studies have focused on the metabolites of different hemp seed varieties. In the current study, using widely targeted metabolomics based on UHPLC-QQQ-MS/MS, we compared the metabolomes of seeds from seven hemp varieties with different uses. A total of 1,001 metabolites, including 201 flavonoids, 86 alkaloids, and 149 phenolic acids, were identified. Flavonoids, organic acids, alkaloids, lipids, and fatty acids with high nutritional value are important to investigate the differences between hemp accessions. By using weighted gene co-expression network analysis (WGCNA), six modules of closely related metabolites were identified. And, we identified the metabolite characteristics and hub metabolites of each variety. Then, we experimentally determined antioxidant activity of seven varieties and demonstrated that alkaloids, flavonoids, phenolic acids, terpenes, and free fatty acids are responsible for the antioxidant activity of hemp seeds. Our research provides useful information for further investigation of the chemical composition of hemp seeds.
ABSTRACT
The spermatogenesis of crustaceans includes nuclear deformation and acrosome formation. The mechanism of acrosome formation is one focus of reproductive biology. In this study, Macrobrachium rosenbergii was selected as the research object to explore the mechanism of acrosome formation. The acrosome contains a large number of acrosomal enzymes for the hydrolysis of the egg envelope. How these acrosomal enzymes are transported to the acrosomal site after synthesis is the key scientific question of this study. The acroframosome (AFS) structure of caridean sperm has been reported. We hypothesized that acrosomal enzymes may be transported along the AFS framework to the acrosome by motor proteins. To study this hypothesis, we obtained the full-length cDNA sequences of Mr-kifc1 and Mr-Acrosin from the testis of M. rosenbergii. The Mr-kifc1 and Mr-Acrosin mRNA expression levels were highest in testis. We detected the distribution of Mr-KIFC1 and its colocalization with Mr-Acrosin during spermatogenesis by immunofluorescence. The colocalization of Mr-KIFC1 and microtubule indicated that Mr-KIFC1 may participate in sperm acrosome formation and nucleus maturation. The colocalization of Mr-KIFC1 and Mr-Acrosin indicated that Mr-KIFC1 may be involved in Acrosin transport during spermiogenesis of M. rosenbergii. These results suggest that Mr-KIFC1 may be involved in acrosomal enzymes transport during spermiogenesis of M. rosenbergii.
ABSTRACT
Oxygen is an essential molecule for animal respiration, growth, and survival. Unlike in terrestrial environments, contamination and climate change have led to the frequent occurrence of hypoxia in aquatic environments, thus impacting aquatic animal survival. However, the adaptative mechanisms underlying fish responses to environmental hypoxia remain largely unknown. Here, we used large yellow croaker ( Larimichthys crocea) and large yellow croaker fry (LYCF) cells to investigate the roles of the Hif-1α/Hsf1/Hsp70 signaling pathway in the regulation of cellular redox homeostasis, and apoptosis. We confirmed that hypoxia induced the expression of Hif-1α, Hsf1, and Hsp70 in vivo and in vitro. Genetic Hsp70 knockdown/overexpression indicated that Hsp70 was required for maintaining redox homeostasis and resisting oxidative stress in LYCF cells under hypoxic stress. Hsp70 inhibited caspase-dependent intrinsic apoptosis by maintaining normal mitochondrial membrane potential, enhancing Bcl-2 mRNA and protein expression, inhibiting Bax and caspase3 mRNA expression, and suppressing caspase-3 and caspase-9 activation. Hsp70 suppressed caspase-independent intrinsic apoptosis by inhibiting nuclear translocation of apoptosis-inducing factor (AIF) and disturbed extrinsic apoptosis by inactivating caspase-8. Genetic knockdown/overexpression of Hif-1α and dual-luciferase reporter assay indicated that Hif-1α activated the Hsf1 DNA promoter and enhanced Hsf1 mRNA transcription. Hsf1 enhanced Hsp70 mRNA transcription in a similar manner. In summary, the Hif-1α/Hsf1/Hsp70 signaling pathway plays an important role in regulating redox homeostasis and anti-apoptosis in L. crocea under hypoxic stress.
Subject(s)
Heat Shock Transcription Factors/metabolism , Homeostasis/physiology , Hypoxia-Inducible Factor 1, alpha Subunit/metabolism , Oxygen/pharmacology , Perciformes/metabolism , Signal Transduction/physiology , Animals , Apoptosis , Cell Line , Cloning, Molecular , Computational Biology , Gene Expression Regulation/drug effects , Heat Shock Transcription Factors/genetics , Homeostasis/drug effects , Hypoxia-Inducible Factor 1, alpha Subunit/genetics , Oxidation-Reduction , Oxygen/chemistry , Perciformes/genetics , RNA, Messenger/genetics , RNA, Messenger/metabolism , Water/chemistryABSTRACT
The mechanism of acrosome formation in the crab sperm is a hot topic in crustacean reproduction research. Dynein is a motor protein that performs microtubule-dependent retrograde transport and plays an essential role in spermatogenesis. However, whether cytoplasmic dynein participates in acrosome formation in the crab sperm remains poorly understood. In this study, we cloned the cytoplasmic dynein intermediate chain gene (Pt-DIC) from Portunus trituberculatus testis. Pt-DIC is composed of a p150glued-binding domain, a dynein light chain (DLC)-binding domain, and a dynein heavy chain (DHC)-binding domain. The Pt-DIC gene is widely expressed in different tissues, showing the highest expression in the testis, and it is expressed in different stages of spermatid development, indicating important functions in spermatogenesis. We further observed the colocalization of Pt-DIC and Pt-DHC, Pt-DHC and tubulin, and Pt-DHC and GM130, and the results indicated that cytoplasmic dynein may participate in nuclear shaping and acrosome formation via vesicle transport. In addition, we examined the colocalization of Pt-DHC and a mitochondrion (MT) tracker and that of Pt-DHC and prohibitin (PHB). The results indicated that cytoplasmic dynein participated in mitochondrial transport and mitochondrial degradation. Taken together, these results support the hypothesis that cytoplasmic dynein participates in acrosome formation, nuclear shaping, and mitochondrial transport during spermiogenesis in P. trituberculatus. This study will provide valuable guidance for the artificial fertilization and reproduction of P. trituberculatus.
Subject(s)
Cytoplasmic Dyneins/genetics , Spermatogenesis/genetics , Animals , BrachyuraABSTRACT
The large yellow croaker (Larimichthys crocea), which is an economically important mariculture fish in China, is often exposed to environmental hypoxia. Reactive oxygen species (ROS) homeostasis is essential for the maintenance of normal physiological conditions in an organism. Direct evidence that environmental hypoxia leads to ROS overproduction is scarce in marine fish. Furthermore, the sources of ROS overproduction in marine fish under hypoxic stress are poorly known. In this study, we investigated the effects of hypoxia on redox homeostasis in L. crocea and the impact of impaired redox homeostasis on fish. We first confirmed that hypoxia drove ROS production mainly via the mitochondrial electron transport chain and NADPH oxidase complex pathways in L. crocea and its cell line (large yellow croaker fry (LYCF) cells). We subsequently detected a marked increase in the antioxidant systems of the fish. However, imbalance between the pro-oxidation and antioxidation systems ultimately led to excessive ROS and oxidative stress. Cell viability showed a remarkable decrease while oxidative indicators, such as malondialdehyde, protein carbonylation, and 8-hydroxy-2 deoxyguanosine, showed a significant increase after hypoxia, accompanied by tissue damage. N-acetylcysteine (NAC) reduced ROS levels, alleviated oxidative damage, and improved cell viability in vitro. Appropriate uptake of ROS scavengers (e.g., NAC and elamipretide Szeto-Schiller-31) and inhibitors (e.g., apocynin, diphenylene iodonium, and 5-hydroxydecanoate) may be effective at overcoming hypoxic toxicity. Our findings highlight previously unstudied strategies of hypoxic toxicity resistance in marine fish.
Subject(s)
Antioxidants/metabolism , Fishes/metabolism , Oxidative Stress/physiology , Oxygen/chemistry , Oxygen/metabolism , Reactive Oxygen Species , Animals , Cell Line , Cell Survival , Environment , Homeostasis , NADPABSTRACT
DNA-damaging agents, such as doxorubicin (Adriamycin), are widely used for the treatment of small cell lung cancer (SCLC). However, drug resistance is one of the major challenges for treatment of SCLC. Herein, we investigated the mechanisms underlying drug resistance in SCLC cells and the effects of resveratrol (Res) on drug resistance. We report that Adriamycin treatment of H69AR (multidrug resistance phenotype) cells resulted in a lower rate of growth inhibition, up-regulation of MRP1 and P-glycoprotein (P-gp), and higher P-gp activity as compared with susceptible H69 cells treated with Adriamycin. Moreover, the signal transducer and activator of transcription 3/vascular endothelial growth factor (STAT3/VEGF) pathway was overactivated in H69AR cells, especially after interleukin-23 treatment. The inflammatory microenvironment promoted the drug resistance of H69AR cells by activating the STAT3/VEGF pathway. The addition of Res suppressed the expression levels of inflammatory mediators, inhibited the STAT3/VEGF pathway, impeded P-gp activity, and decreased the drug resistance of H69AR cells. H69AR cells exhibited Adriamycin resistance through activation of the STAT3/VEGF pathway, and Res ameliorated the inflammatory microenvironment to suppress the STAT3/VEGF pathway to reduce drug resistance. Our results suggest that Res may have therapeutic potential for SCLC treatment.
ABSTRACT
The prevalence of Heart Failure (HF) has increased over time. Ischemic heart failure accounts for 50% of HF, which results from ischemic coronary heart diseases such as Myocardial Infarction (MI). Conventionally, reduction of cardiac load and revascularization partially increase cardiomyocyte survival and preserve cardiac functions. Nevertheless, how to improve cardiomyocyte rescue and prevent HF progression remain as challenges. Mesenchymal Stem Cells (MSCs) are multipotent stem cells that give rise to various lineages. The administration of MSCs promotes cardiomyocyte survival and improves cardiac functions in animal models of MI and patients with ischemic cardiomyopathy. However, after injection, MSCs persist for a very short time, indicating that the prolonged protective effects of MSCs on cardiomyocytes may be mediated by paracrine functions of MSCs, such as exosomes. In this review, we focus on MSC-derived exosomes in cardiomyocyte protection to facilitate future applications of exosomes in HF treatment.
Subject(s)
Heart Failure , Mesenchymal Stem Cell Transplantation , Mesenchymal Stem Cells , Myocardial Infarction , Animals , Heart Failure/therapy , Humans , Myocardial Infarction/therapy , Myocytes, CardiacABSTRACT
Emission from burning coals is one of the major sources of the airborne particles in China. We carried out a study on the rare earth elements (REEs) in the inhalable particulate matter (PM10) emitted from burning coals and soil-coal honeycomb briquettes with different volatile contents and ash yields in a combustion-dilution system. Gravimetric analysis indicates that the equivalent mass concentration of the PM10 emitted from burning the coals is higher than that emitted from burning the briquettes. The ICP-MS analysis indicates that the contents of total REEs in the coal-burning PM10 are lower than those in the briquette-burning PM10. In addition, the contents of the light rare earth elements (LREEs) are higher than those of the heavy rare earth elements (HREEs) in the PM10 emitted from burning the coals and briquettes, demonstrating that the REEs in both the coal-burning and briquette-burning PM10 are dominated by LREEs. The higher contents of total REEs and LREEs in the coal-burning PM10 are associated with the higher ash yields and lower volatile contents in the raw coals. A comparative analysis indicates that the La/Sm ratios in the PM10 emitted from burning the coals and briquettes, being lower than 2, are lower than those in the particles from gasoline-powered vehicle emission.