Small interfering RNAs(siRNA)provide a novel and highly specific therapy due to their ability to effectively silence target genes,to date six siRNA therapeutics are approved for clinical use.Even so,some critical chal...Small interfering RNAs(siRNA)provide a novel and highly specific therapy due to their ability to effectively silence target genes,to date six siRNA therapeutics are approved for clinical use.Even so,some critical challenges remain to overcome in the therapeutic application of siRNAs,with delivery issues at the forefront.Among them,endo/lysosomal barrier is one of the important but often-neglected limitations hindering the delivery of siRNA therapeutics.In this review,we summarize the promising strategies that facilitate siRNAs overcoming endo/lysosomal barriers based on the cellular uptake and intracellular transport pathways,including promoting escape once endocytosis into the endo/lysosomes and bypassing lysosomes via endosome-Golgi-endoplasmic reticulum(ER)pathway or nonendocytosis pathway,and discuss the principal considerations and the future directions of promoting endo/lysosomal escape in the development of therapeutic siRNAs.展开更多
Background: The incidence of alcohol-associated cancers is higher within Asian populations having an increased prevalence ofan inactivating mutation in aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme required...Background: The incidence of alcohol-associated cancers is higher within Asian populations having an increased prevalence ofan inactivating mutation in aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme required for the clearance of acetaldehyde, a cytotoxic metabolite of ethanol. The role of alcohol consumption in promoting lung cancer is controversial, andlittle attention has been paid to the association between alcohol drinking and pulmonary ALDH2 expression.Methods: We performed a comprehensive bioinformatic analysis of multi-omics data available in public databases to elucidatethe role of ALDH2 in lung adenocarcinoma (LUAD).Results: Transcriptional and proteomic data indicate a substantial pulmonary expression of ALDH2, which is functional for themetabolism of alcohol diffused from the bronchial circulation. ALDH2 expression is higher in healthy lung tissue than in LUADand inhibits cell cycle, apoptosis, and epithelial–mesenchymal transition pathways. Moreover, low ALDH2 mRNA levels predictpoor prognosis and low overall survival in LUAD patients. Interestingly, ALDH2 expression correlates with immune infiltrationin LUAD.Conclusions: A better understanding of the role of ALDH2 in lung tumor progression and immune infiltration might supportits potential use as a prognostic marker and therapeutic target for improving immunotherapeutic response.展开更多
Fifty years after the introduction of Bacillus Calmette-Guérin(BCG),a live attenuated strain of Mycobacterium bovis[1],it is still the most effective and successful adjuvant immunotherapy of non-muscle invasive b...Fifty years after the introduction of Bacillus Calmette-Guérin(BCG),a live attenuated strain of Mycobacterium bovis[1],it is still the most effective and successful adjuvant immunotherapy of non-muscle invasive bladder cancer(NMIBC)[2].The guidelines of the European Association of Urology(EAU)suggest a 6-weekly induction phase followed by a maintenance schedule of BCG once weekly for 3 weeks and at 3,6,12,18,24,30,and 36 months for 1 to 3 years[2].展开更多
基金supported by National Natural Science Foundation of China(No.82173769)the National Key R&D Program of China(No.2021YFE0106900)+1 种基金Applied Basic Research Multiinvestment Foundation of Tianjin(No.21JCYBJC01540)the Science&Technology Development Fund of Tianjin Education Commission for Higher Education(No.2023ZD019)。
文摘Small interfering RNAs(siRNA)provide a novel and highly specific therapy due to their ability to effectively silence target genes,to date six siRNA therapeutics are approved for clinical use.Even so,some critical challenges remain to overcome in the therapeutic application of siRNAs,with delivery issues at the forefront.Among them,endo/lysosomal barrier is one of the important but often-neglected limitations hindering the delivery of siRNA therapeutics.In this review,we summarize the promising strategies that facilitate siRNAs overcoming endo/lysosomal barriers based on the cellular uptake and intracellular transport pathways,including promoting escape once endocytosis into the endo/lysosomes and bypassing lysosomes via endosome-Golgi-endoplasmic reticulum(ER)pathway or nonendocytosis pathway,and discuss the principal considerations and the future directions of promoting endo/lysosomal escape in the development of therapeutic siRNAs.
基金uropean Foundation for Alcohol Research(Grant:EA 1719)。
文摘Background: The incidence of alcohol-associated cancers is higher within Asian populations having an increased prevalence ofan inactivating mutation in aldehyde dehydrogenase 2 (ALDH2), a mitochondrial enzyme required for the clearance of acetaldehyde, a cytotoxic metabolite of ethanol. The role of alcohol consumption in promoting lung cancer is controversial, andlittle attention has been paid to the association between alcohol drinking and pulmonary ALDH2 expression.Methods: We performed a comprehensive bioinformatic analysis of multi-omics data available in public databases to elucidatethe role of ALDH2 in lung adenocarcinoma (LUAD).Results: Transcriptional and proteomic data indicate a substantial pulmonary expression of ALDH2, which is functional for themetabolism of alcohol diffused from the bronchial circulation. ALDH2 expression is higher in healthy lung tissue than in LUADand inhibits cell cycle, apoptosis, and epithelial–mesenchymal transition pathways. Moreover, low ALDH2 mRNA levels predictpoor prognosis and low overall survival in LUAD patients. Interestingly, ALDH2 expression correlates with immune infiltrationin LUAD.Conclusions: A better understanding of the role of ALDH2 in lung tumor progression and immune infiltration might supportits potential use as a prognostic marker and therapeutic target for improving immunotherapeutic response.
文摘Fifty years after the introduction of Bacillus Calmette-Guérin(BCG),a live attenuated strain of Mycobacterium bovis[1],it is still the most effective and successful adjuvant immunotherapy of non-muscle invasive bladder cancer(NMIBC)[2].The guidelines of the European Association of Urology(EAU)suggest a 6-weekly induction phase followed by a maintenance schedule of BCG once weekly for 3 weeks and at 3,6,12,18,24,30,and 36 months for 1 to 3 years[2].
