Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmet...Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.展开更多
A team of researchers from the Beijing Normal University,the Institute of High Energy Physics(IHEP)under the Chinese Academy of Sciences(CAS),and the National Astronomical Observatories,CAS(NAOC),reported in Nature As...A team of researchers from the Beijing Normal University,the Institute of High Energy Physics(IHEP)under the Chinese Academy of Sciences(CAS),and the National Astronomical Observatories,CAS(NAOC),reported in Nature Astronomy on January 23,2025 their discovery of an X-ray flash about 12.5 billion lightyears away.The signals burst out only 1.2 billion years after the Big Bang,when our 13.8-billion-year-old universe was still in its infancy,and a science satellite swiftly recorded them.展开更多
IM To study VEGF mRNA expression in gastric carcinoma and to clarify the association of its expression with the clinicopathologic features of the disease.METHODS In situ hybridization (ISH) and histochemistry were u...IM To study VEGF mRNA expression in gastric carcinoma and to clarify the association of its expression with the clinicopathologic features of the disease.METHODS In situ hybridization (ISH) and histochemistry were used to examine and analyze the expression of VEGF mRNA and antigen, and microvessel count (MVC) in 28 cases of gastric carcinomatous tissue in combination with clinical materials.RESULTS Ninteen of 28 gastric carcinomas were positive for VEGF mRNA. VEGF mRNA was mainly expressed in malignant cells and not in normal epithelium of gastric mucosa. Its expression was further increased in tumor cells adjacent to tumor necrosis zones, where stromal cells expressed VEGF mRNA occasionally. There was a close correlation between MVC and VEGF mRNA positivity (P<0005). High VEGF mRNA levels were significantly associated with serosal invasion, lymph node metastasis and TNM staging (P<005, respectively).CONCLUSION VEGF mRNA expression is associated with tumor invasion and metastasis by stimulating angiogenesis in gastric carcinoma.expression; endothelial growth factor.展开更多
AIM To investigate alpha-fetoprotein (AFP) mRNA expression in BEL-7404 human hepatoma cells and the effect of L-4-oxalysine (OXL) on the expression.METHODS BEl-7404 human hepatoma cells were maintained in RPMI 1640 me...AIM To investigate alpha-fetoprotein (AFP) mRNA expression in BEL-7404 human hepatoma cells and the effect of L-4-oxalysine (OXL) on the expression.METHODS BEl-7404 human hepatoma cells were maintained in RPMI 1640 media. Human AFP cDNA probe was labelled with digoxigenin-11-dUTP by the random primer labelling method. The expression of AFP mRNA in Bel-7404 cells was determined by an in situ hybridization technique with digoxigenin-labelled human AFP cDNA probe. The positive intensities of AFP mRNA in cells were analyzed by microspectrophotometer and expressed as absorbance at 470nm. For the experiment with OXL, cells were incubated with various concentrations of the agent for 72h.RESULTS Essentially all the hepatoma cells contained AFP mRNA in the cytoplasm, although in various amounts. The specificity of the hybridization reaction was confirmed by control experiments in which the use of RNase-treated BEL-7404 cells, non-AFP-producing cells (HL-60 human leukemia cells) or a nonspecific cDNA probe resulted in negative hybridization. When the cells were treated with OXL (25, 50mg/L), the content of AFP mRNA in the cytoplasm was decreased with the inhibition percentages of 34.3% and 70.1%, respectively (P＜0.05).CONCLUSION AFP mRNA was expressed in BEL-7404 human hepatoma cells and OXL suppressed AFP mRNA expression in the cells.展开更多
OBJECTIVE: To profile the liver cancer specific long noncoding RNAs(lnc RNAs) and competing endogenous RNA(ce RNA) networks of Hepatitis B virus(HBV)-associated hepatocarcinogensis(HCG) and to examine the effect of co...OBJECTIVE: To profile the liver cancer specific long noncoding RNAs(lnc RNAs) and competing endogenous RNA(ce RNA) networks of Hepatitis B virus(HBV)-associated hepatocarcinogensis(HCG) and to examine the effect of compound K on the expression of identified ce RNA networks.METHODS: Based on lnc RNA and messenger RNA(m RNA) microarray data of HBV-associated liver cancer, the current study profiles the cancer specific lnc RNAs and ce RNA networks of HBV-associated HCG through comprehensive application of Reg RNA 2, mi RTar Base and Pearson correlation coefficient analysis. Compound K-treated liver cancer cells were harvested for analysis of transcriptional levels of both enoyl-Co A hydratase and 3-hydroxyacyl Co A dehydrogenase(EHHADH)-AS1 and ENTPD5.RESULTS: The results revealed that 11 Encyclopedia of DNA Elements annotated lnc RNAs were differentially expressed in the process of HBV-associated HCG. Among these lnc RNAs, 95 potential ce RNA networks with highly positively correlated expression profiles between the interacting lnc RNAs and m RNAs(Pearson correlation coefficient ≥ 0.7) were constructed. Of note, two HBV-associated ce RNA networks, EHHADH-AS1-hsa-mi R-4459-ectonucleoside triphosphate diphosphohydrolase 5 and LINC01018-hsa-mi RNA-574-5p-glucose-6-phosphatase catalytic subunit, with Pearson correlation coefficient ≥ 0.9, may play a critical role in hepatocellular carcinoma development, which was supported by experimental evidence. Interestingly, compound K, an intestinal bacterial metabolite of ginseng protopanaxadiol saponin, which has been proven to promote apoptosis of human hepatocellular carcinoma cells, was found to impede the down-regulation of EHHADH-AS1 in several liver cancer cell lines including Hep G3 B, Huh-7 and plc/prf/5 cells.CONCLUSION: Comprehensive application of co-expression network analysis and prediction of RNA interaction may be a feasible strategy to unravel the potential ce RNA networks involved in the process of human diseases.展开更多
AIM:To assess effects of heme on messenger RNA(mRNA) and microRNA(miRNA) profiles of liver cells derived from humans.METHODS:We exposed human hepatoma cell line Huh-7 cells to excess iron protoporphyrin(heme)(10 μmol...AIM:To assess effects of heme on messenger RNA(mRNA) and microRNA(miRNA) profiles of liver cells derived from humans.METHODS:We exposed human hepatoma cell line Huh-7 cells to excess iron protoporphyrin(heme)(10 μmol/L) or induced heme deficiency by addition of 4,6-dioxoheptanoic acid(500 μmol/L),a potent inhibitor of aminolevulinic acid dehydratase,for 6 h or 24 h.We harvested total RNA from the cells and performed both mRNA and miRNA array analyses,with use of Affymetrix chips,reagents,and instruments(human genome U133 plus 2.0 and miRNA 2.0 arrays).We assessed changes and their significance and interrelationships with Target Scan,Pathway Studios,and Ingenuity software.RESULTS:Changes in mRNA levels were most numerous and striking at 6 h after heme treatment but were similar and still numerous at 24 h.After 6 h of heme exposure,the increase in heme oxygenase 1 gene expression was 60-fold by mRNA and 88-fold by quantitative reverse transcription-polymerase chain reaction.We found striking changes,especially up-regulation by heme of nuclear erythroid-2 related factor-mediated oxidative stress responses,protein ubiquitination,glucocorticoid signaling,P53 signaling,and changes in RNAs that regulate intermediary metabolism.Fewer mRNAs were down-regulated by heme,and the fold decreases were less exuberant than were the increases.Notable decreases after 24 h of heme exposure were patatin-like phospholipase domain-containing protein 3(-6.5-fold),neuronal PAS domain protein 2(-1.93-fold),and protoporphyrinogen oxidase(-1.7-fold).CONCLUSION:Heme excess exhibits several toxic effects on liver and kidney,which deserve study in humans and in animal models of the human porphyrias or other disorders.展开更多
Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of ...Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass.However,consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown.We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2-and 9-mo mice.The cancellous bone mass is higher only in females,whereas,cortical bone mass is higher in 2-and 9-mo males,but higher in 2-and lower in 9-mo female FMR1-knockout mice.Furthermore,male bones show higher biomechanical properties at 2mo,and females at both ages.Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro,without affecting osteoclasts in vivo/ex vivo.Thus,FMR1 is a novel osteoblast/osteocyte differentiation inhibitor,and its absence leads to age-,site-and sex-dependent higher bone mass/strength.展开更多
文摘Tuberculosis(TB)remains a critical global health challenge,with 10.8 million new cases and over 1.25 million deaths reported annually,disproportionately affecting low-income regions.Despite its use,the Bacillus Calmette-Guérin(BCG)vaccine provides limited protection against adult pulmonary TB,necessitating novel solutions.The messenger RNA(mRNA)vaccine technology,proven effective in combating coronavirus disease 2019,offers significant promise for TB prevention.These vaccines elicit robust immune responses by encoding antigens that stimulate humoral and cell-mediated immunity,essential for combating mycobacterium TB.Unlike traditional methods,mRNA vaccines are highly adaptable,scalable,and capable of targeting emerging strains.Preclinical studies highlight the enhanced efficacy of mRNA TB vaccines over BCG,demonstrating their ability to reduce bacterial burdens and generate memory T-cell responses critical for long-term protection.However,challenges persist,including mRNA instability,cold-chain storage needs,and mycobacterium’s complex immune evasion strategies.Innovative solutions,such as lipid nanoparticle delivery systems and selfamplifying mRNA platforms,are being developed to address these barriers.The initiation of clinical trials,notably BioNTech’s BNT164,marks a pivotal advancement in TB vaccine development.These trials focus on safety,immuno genicity,and efficacy,particularly in regions with high TB prevalence.While logistical and financial hurdles remain,mRNA vaccines hold transformative potential to bridge critical gaps in TB prevention.Their adaptability extends to tackling co-infections like human immunodeficiency virus,further amplifying their impact on global health.By integrating mRNA vaccines into existing TB control strategies,these advancements could revolutionize prevention efforts,especially in regions where current solutions fall short.Continued innovation and investment are crucial to harnessing the full potential of mRNA vaccines,positioning them as a cornerstone in the fight against TB and its global eradication.
文摘A team of researchers from the Beijing Normal University,the Institute of High Energy Physics(IHEP)under the Chinese Academy of Sciences(CAS),and the National Astronomical Observatories,CAS(NAOC),reported in Nature Astronomy on January 23,2025 their discovery of an X-ray flash about 12.5 billion lightyears away.The signals burst out only 1.2 billion years after the Big Bang,when our 13.8-billion-year-old universe was still in its infancy,and a science satellite swiftly recorded them.
文摘IM To study VEGF mRNA expression in gastric carcinoma and to clarify the association of its expression with the clinicopathologic features of the disease.METHODS In situ hybridization (ISH) and histochemistry were used to examine and analyze the expression of VEGF mRNA and antigen, and microvessel count (MVC) in 28 cases of gastric carcinomatous tissue in combination with clinical materials.RESULTS Ninteen of 28 gastric carcinomas were positive for VEGF mRNA. VEGF mRNA was mainly expressed in malignant cells and not in normal epithelium of gastric mucosa. Its expression was further increased in tumor cells adjacent to tumor necrosis zones, where stromal cells expressed VEGF mRNA occasionally. There was a close correlation between MVC and VEGF mRNA positivity (P<0005). High VEGF mRNA levels were significantly associated with serosal invasion, lymph node metastasis and TNM staging (P<005, respectively).CONCLUSION VEGF mRNA expression is associated with tumor invasion and metastasis by stimulating angiogenesis in gastric carcinoma.expression; endothelial growth factor.
文摘AIM To investigate alpha-fetoprotein (AFP) mRNA expression in BEL-7404 human hepatoma cells and the effect of L-4-oxalysine (OXL) on the expression.METHODS BEl-7404 human hepatoma cells were maintained in RPMI 1640 media. Human AFP cDNA probe was labelled with digoxigenin-11-dUTP by the random primer labelling method. The expression of AFP mRNA in Bel-7404 cells was determined by an in situ hybridization technique with digoxigenin-labelled human AFP cDNA probe. The positive intensities of AFP mRNA in cells were analyzed by microspectrophotometer and expressed as absorbance at 470nm. For the experiment with OXL, cells were incubated with various concentrations of the agent for 72h.RESULTS Essentially all the hepatoma cells contained AFP mRNA in the cytoplasm, although in various amounts. The specificity of the hybridization reaction was confirmed by control experiments in which the use of RNase-treated BEL-7404 cells, non-AFP-producing cells (HL-60 human leukemia cells) or a nonspecific cDNA probe resulted in negative hybridization. When the cells were treated with OXL (25, 50mg/L), the content of AFP mRNA in the cytoplasm was decreased with the inhibition percentages of 34.3% and 70.1%, respectively (P＜0.05).CONCLUSION AFP mRNA was expressed in BEL-7404 human hepatoma cells and OXL suppressed AFP mRNA expression in the cells.
基金Supported by the Natural Science Foundation of China:The roles and mechanisms of RXRαin HBx-induced DNMT3a up-regulation in hepatocellular carcinoma(No.81372272)The role of Foxo1-m TOR signal axis in regulating bioenergetic metabolism transition during NK Cell activation(No.81520108029)
文摘OBJECTIVE: To profile the liver cancer specific long noncoding RNAs(lnc RNAs) and competing endogenous RNA(ce RNA) networks of Hepatitis B virus(HBV)-associated hepatocarcinogensis(HCG) and to examine the effect of compound K on the expression of identified ce RNA networks.METHODS: Based on lnc RNA and messenger RNA(m RNA) microarray data of HBV-associated liver cancer, the current study profiles the cancer specific lnc RNAs and ce RNA networks of HBV-associated HCG through comprehensive application of Reg RNA 2, mi RTar Base and Pearson correlation coefficient analysis. Compound K-treated liver cancer cells were harvested for analysis of transcriptional levels of both enoyl-Co A hydratase and 3-hydroxyacyl Co A dehydrogenase(EHHADH)-AS1 and ENTPD5.RESULTS: The results revealed that 11 Encyclopedia of DNA Elements annotated lnc RNAs were differentially expressed in the process of HBV-associated HCG. Among these lnc RNAs, 95 potential ce RNA networks with highly positively correlated expression profiles between the interacting lnc RNAs and m RNAs(Pearson correlation coefficient ≥ 0.7) were constructed. Of note, two HBV-associated ce RNA networks, EHHADH-AS1-hsa-mi R-4459-ectonucleoside triphosphate diphosphohydrolase 5 and LINC01018-hsa-mi RNA-574-5p-glucose-6-phosphatase catalytic subunit, with Pearson correlation coefficient ≥ 0.9, may play a critical role in hepatocellular carcinoma development, which was supported by experimental evidence. Interestingly, compound K, an intestinal bacterial metabolite of ginseng protopanaxadiol saponin, which has been proven to promote apoptosis of human hepatocellular carcinoma cells, was found to impede the down-regulation of EHHADH-AS1 in several liver cancer cell lines including Hep G3 B, Huh-7 and plc/prf/5 cells.CONCLUSION: Comprehensive application of co-expression network analysis and prediction of RNA interaction may be a feasible strategy to unravel the potential ce RNA networks involved in the process of human diseases.
基金Supported by A Grant from NIH/NIDDK (DK38825) to Bonkovsky HLInstitutional Funds from the Carolinas Health Care Foundation and Carolinas Medical Center
文摘AIM:To assess effects of heme on messenger RNA(mRNA) and microRNA(miRNA) profiles of liver cells derived from humans.METHODS:We exposed human hepatoma cell line Huh-7 cells to excess iron protoporphyrin(heme)(10 μmol/L) or induced heme deficiency by addition of 4,6-dioxoheptanoic acid(500 μmol/L),a potent inhibitor of aminolevulinic acid dehydratase,for 6 h or 24 h.We harvested total RNA from the cells and performed both mRNA and miRNA array analyses,with use of Affymetrix chips,reagents,and instruments(human genome U133 plus 2.0 and miRNA 2.0 arrays).We assessed changes and their significance and interrelationships with Target Scan,Pathway Studios,and Ingenuity software.RESULTS:Changes in mRNA levels were most numerous and striking at 6 h after heme treatment but were similar and still numerous at 24 h.After 6 h of heme exposure,the increase in heme oxygenase 1 gene expression was 60-fold by mRNA and 88-fold by quantitative reverse transcription-polymerase chain reaction.We found striking changes,especially up-regulation by heme of nuclear erythroid-2 related factor-mediated oxidative stress responses,protein ubiquitination,glucocorticoid signaling,P53 signaling,and changes in RNAs that regulate intermediary metabolism.Fewer mRNAs were down-regulated by heme,and the fold decreases were less exuberant than were the increases.Notable decreases after 24 h of heme exposure were patatin-like phospholipase domain-containing protein 3(-6.5-fold),neuronal PAS domain protein 2(-1.93-fold),and protoporphyrinogen oxidase(-1.7-fold).CONCLUSION:Heme excess exhibits several toxic effects on liver and kidney,which deserve study in humans and in animal models of the human porphyrias or other disorders.
基金supported by the National Institutes of Health R01-AR053643Veterans Research Administration Merit Award I01BX00515+7 种基金a Research Support Funds Grant(RSFG),Indiana University Purdue University Indianapolis-Office of the Vice Chancellor for Research,Indianapolis to LIP.supported by ASBMR Fund for Research and Education Research and Collaborative Grant Programsupported by the National Institutes of Health R01AG067997 to CJHsupported by the IUPUI Diversity Scholars Research Program(DSRP)Diversity Summer Undergraduate Research Opportunity Program(DS-UROP)Indiana CTSI Student Summer Research ProgramIUPUI work study programsupported by the Life Health Science Internship(LHSI)。
文摘Fragile X Messenger Ribonucleoprotein 1(FMR1)gene mutations lead to fragile X syndrome,cognitive disorders,and,in some individuals,scoliosis and craniofacial abnormalities.Four-month-old(mo)male mice with deletion of the FMR1 gene exhibit a mild increase in cortical and cancellous femoral bone mass.However,consequences of absence of FMR1 in bone of young/aged male/female mice and the cellular basis of the skeletal phenotype remain unknown.We found that absence of FMR1 results in improved bone properties with higher bone mineral density in both sexes and in 2-and 9-mo mice.The cancellous bone mass is higher only in females,whereas,cortical bone mass is higher in 2-and 9-mo males,but higher in 2-and lower in 9-mo female FMR1-knockout mice.Furthermore,male bones show higher biomechanical properties at 2mo,and females at both ages.Absence of FMR1 increases osteoblast/mineralization/bone formation and osteocyte dendricity/gene expression in vivo/ex vivo/in vitro,without affecting osteoclasts in vivo/ex vivo.Thus,FMR1 is a novel osteoblast/osteocyte differentiation inhibitor,and its absence leads to age-,site-and sex-dependent higher bone mass/strength.
