BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for...BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.展开更多
BACKGROUND New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of n...BACKGROUND New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin(CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects.AIM To obtain a deeper understanding of CAM, its distribution, metabolism and antiinflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method.METHODS In this paper, the content of isovaleryl spiramycin Ⅲ was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses.RESULTS The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4(IL-4) levels in the lung and kidney and especially the liver and spleen;moreover, CAM significantly reduced the IL-1β levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets,such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases.CONCLUSION We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.展开更多
Carrimycin is a synthetic macrolide antibiotic that has been shown to have anti-cancer activity;however,its exact mechanism of action and molecular target were previously unknown.It was recently elucidated that Isoval...Carrimycin is a synthetic macrolide antibiotic that has been shown to have anti-cancer activity;however,its exact mechanism of action and molecular target were previously unknown.It was recently elucidated that Isovalerylspiramycin I(ISP I),the active component of carrimycin,targets selenoprotein H(SelH),a nucleolar reactive oxygen species-scavenging enzyme in the selenoprotein family.ISP I treatment accelerates SelH degradation,resulting in oxidative stress,disrupted ribosomal biogenesis,and apoptosis in tumor cells.Specifically,ISP I disrupts the association between RNA polymerase I and ribosomal DNA in the nucleolus.This inhibits ribosomal RNA transcription and subsequent ribosomal assembly,which prevents cancer cells from sustaining elevated rates of protein synthesis and cellular proliferation that are necessary for tumor growth and malignancy.In this review,we(1)describe the historical categorization and evolution of anti-cancer agents,including macrolide antibiotics,(2)outline the discovery of SelH as a target of ISP I,and(3)summarize the ways in which carrimycin has been used both clinically and at the bench to date and propose additional potential therapeutic uses.展开更多
COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development.No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infection...COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development.No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections.We report herein that a macrolide antibiotic,carrimycin,potently inhibited the cytopathic effects(CPE)and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229 E,OC43,and SARS-CoV-2.Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection.In support of this notion,metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA.Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.展开更多
Carrimycin(CA),sanctioned by China’s National Medical Products Administration(NMPA)in 2019 for treating acute bronchitis and sinusitis,has recently been observed to exhibit multifaceted biological activities,encompas...Carrimycin(CA),sanctioned by China’s National Medical Products Administration(NMPA)in 2019 for treating acute bronchitis and sinusitis,has recently been observed to exhibit multifaceted biological activities,encompassing anti-inflammatory,antiviral,and anti-tumor properties.Despite these applications,its efficacy in sepsis treatment remains unexplored.This study introduces a novel function of CA,demonstrating its capacity to mitigate sepsis induced by lipopolysaccharide(LPS)and cecal ligation and puncture(CLP)in mice models.Our research employed in vitro assays,real-time quantitative polymerase chain reaction(RT-qPCR),and RNA-seq analysis to establish that CA significantly reduces the levels of pro-inflammatory cytokines,namely tumor necrosis factor-alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6),in response to LPS stimulation.Additionally,Western blotting and immunofluorescence assays revealed that CA impedes Nuclear Factor Kappa B(NF-κB)activation in LPS-stimulated RAW264.7 cells.Complementing these findings,in vivo experiments demonstrated that CA effectively alleviates LPS-and CLP-triggered organ inflammation in C57BL/6 mice.Further insights were gained through 16S sequencing,highlighting CA’s pivotal role in enhancing gut microbiota diversity and modulating metabolic pathways,particularly by augmenting the production of short-chain fatty acids in mice subjected to CLP.Notably,a comparative analysis revealed that CA’s anti-inflammatory efficacy surpasses that of equivalent doses of aspirin(ASP)and TIENAM.Collectively,these findings suggest that CA exhibits significant therapeutic potential in sepsis treatment.This discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management.展开更多
文摘BACKGROUND Pulmonary tuberculosis(PTB)is prevalent in immunocompromised populations,including patients with hematologic malignancies,human immunodeficiency virus infections,and chronic diseases.Effective treatment for acute promyelocytic leukemia(APL)combined with PTB is lacking.These patients show an extremely poor prognosis.Therefore,studies should establish efficient treatment options to improve patient survival and prognosis.CASE SUMMARY A 60-year-old male with pain in the right side of his chest and a fever for 4 d visited the outpatient department of our hospital.Peripheral blood smear revealed 54%blasts.Following bone marrow examinations,variant APL with TNRC18-RARA fusion gene was diagnosed.Chest computed tomography scan showed bilateral pneumonitis with bilateral pleural effusions,partial atelectasis in the lower lobes of both lungs,and the bronchoalveolar lavage fluid gene X-Pert test was positive,indicative of PTB.Carrimycin,ethambutol(EMB),and isoniazid(INH)were administered since he could not receive chemotherapy as the WBC count decreased continuously.After one week of treatment with carrimycin,the patient recovered from fever and received chemotherapy.Chemotherapy was very effective and his white blood cells counts got back to normal.After being given five months with rifampin,EMB and INH and chemotherapy,the patient showed complete remission from pneumonia and APL.CONCLUSION We report a case of PTB treated successfully with carrimycin with APL that requires chemotherapy.
基金Supported by Heilongjiang Natural Science Foundation,No.LH2022H085 and H2016057Scientific Research Project of Heilongjiang Health Committee,No.2020-293.
文摘BACKGROUND New drugs are urgently needed for the treatment of liver cancer, a feat that could be feasibly accomplished by finding new therapeutic purposes for marketed drugs to save time and costs. As a new class of national anti-infective drugs, carrimycin(CAM) has strong activity against gram-positive bacteria and no cross resistance with similar drugs. Studies have shown that the components of CAM have anticancer effects.AIM To obtain a deeper understanding of CAM, its distribution, metabolism and antiinflammatory effects were assessed in the organs of mice, and its mechanism of action against liver cancer was predicted by a network pharmacology method.METHODS In this paper, the content of isovaleryl spiramycin Ⅲ was used as an index to assess the distribution and metabolism of CAM and its effect on inflammatory factors in various mouse tissues and organs. Reverse molecular docking technology was utilized to determine the target of CAM, identify each target protein based on disease type, and establish a target protein-disease type network to ascertain the effect of CAM in liver cancer. Then, the key action targets of CAM in liver cancer were screened by a network pharmacology method, and the core targets were verified by molecular docking and visual analyses.RESULTS The maximum CAM concentration was reached in the liver, kidney, lung and spleen 2.5 h after intragastric administration. In the intestine, the maximum drug concentration was reached 0.5 h after administration. In addition, CAM significantly reduced the interleukin-4(IL-4) levels in the lung and kidney and especially the liver and spleen;moreover, CAM significantly reduced the IL-1β levels in the spleen, liver, and kidney and particularly the small intestine and lung. CAM is predicted to regulate related pathways by acting on many targets,such as albumin, estrogen receptor 1, epidermal growth factor receptor and caspase 3, to treat cancer, inflammation and other diseases.CONCLUSION We determined that CAM inhibited inflammation. We also predicted the complex multitargeted effects of CAM that involve multiple pathways and the diversity of these effects in the treatment of liver cancer, which provides a basis and direction for further clinical research.
基金supported in part by the Intramural Program of the NCI and NINDS(National Institutes of Health)and did not receive any specific grant from funding agencies(e.g.,public,commercial,or not-forprofit sectors)outside of the authors'academic institution.
文摘Carrimycin is a synthetic macrolide antibiotic that has been shown to have anti-cancer activity;however,its exact mechanism of action and molecular target were previously unknown.It was recently elucidated that Isovalerylspiramycin I(ISP I),the active component of carrimycin,targets selenoprotein H(SelH),a nucleolar reactive oxygen species-scavenging enzyme in the selenoprotein family.ISP I treatment accelerates SelH degradation,resulting in oxidative stress,disrupted ribosomal biogenesis,and apoptosis in tumor cells.Specifically,ISP I disrupts the association between RNA polymerase I and ribosomal DNA in the nucleolus.This inhibits ribosomal RNA transcription and subsequent ribosomal assembly,which prevents cancer cells from sustaining elevated rates of protein synthesis and cellular proliferation that are necessary for tumor growth and malignancy.In this review,we(1)describe the historical categorization and evolution of anti-cancer agents,including macrolide antibiotics,(2)outline the discovery of SelH as a target of ISP I,and(3)summarize the ways in which carrimycin has been used both clinically and at the bench to date and propose additional potential therapeutic uses.
基金financially supported by CAMS Initiative for Innovative Medicine(2020-I2M-Co V19-008,China)the National Science and Technology Major Projects for“Major New Drugs Innovation and Development”(2018ZX09711003,China)+1 种基金the National Key Research and Development Program of China(2020YFC0844900,China)Fundamental Research Funds for CAMS of China(2020HY320001,China)
文摘COVID-19 pandemic caused by SARS-CoV-2 infection severely threatens global health and economic development.No effective antiviral drug is currently available to treat COVID-19 and any other human coronavirus infections.We report herein that a macrolide antibiotic,carrimycin,potently inhibited the cytopathic effects(CPE)and reduced the levels of viral protein and RNA in multiple cell types infected by human coronavirus 229 E,OC43,and SARS-CoV-2.Time-of-addition and pseudotype virus infection studies indicated that carrimycin inhibited one or multiple post-entry replication events of human coronavirus infection.In support of this notion,metabolic labelling studies showed that carrimycin significantly inhibited the synthesis of viral RNA.Our studies thus strongly suggest that carrimycin is an antiviral agent against a broad-spectrum of human coronaviruses and its therapeutic efficacy to COVID-19 is currently under clinical investigation.
基金supported by the Excellent Young Scholars Cultivation Project of Fujian Medical University Union Hospital in China(No.2022XH031)the National Natural Science Foundation of China(No.82203439)the Natural Science Foundation of Fujian Province(No.2022J01263).
文摘Carrimycin(CA),sanctioned by China’s National Medical Products Administration(NMPA)in 2019 for treating acute bronchitis and sinusitis,has recently been observed to exhibit multifaceted biological activities,encompassing anti-inflammatory,antiviral,and anti-tumor properties.Despite these applications,its efficacy in sepsis treatment remains unexplored.This study introduces a novel function of CA,demonstrating its capacity to mitigate sepsis induced by lipopolysaccharide(LPS)and cecal ligation and puncture(CLP)in mice models.Our research employed in vitro assays,real-time quantitative polymerase chain reaction(RT-qPCR),and RNA-seq analysis to establish that CA significantly reduces the levels of pro-inflammatory cytokines,namely tumor necrosis factor-alpha(TNF-α),interleukin 1 beta(IL-1β),and interleukin 6(IL-6),in response to LPS stimulation.Additionally,Western blotting and immunofluorescence assays revealed that CA impedes Nuclear Factor Kappa B(NF-κB)activation in LPS-stimulated RAW264.7 cells.Complementing these findings,in vivo experiments demonstrated that CA effectively alleviates LPS-and CLP-triggered organ inflammation in C57BL/6 mice.Further insights were gained through 16S sequencing,highlighting CA’s pivotal role in enhancing gut microbiota diversity and modulating metabolic pathways,particularly by augmenting the production of short-chain fatty acids in mice subjected to CLP.Notably,a comparative analysis revealed that CA’s anti-inflammatory efficacy surpasses that of equivalent doses of aspirin(ASP)and TIENAM.Collectively,these findings suggest that CA exhibits significant therapeutic potential in sepsis treatment.This discovery provides a foundational theoretical basis for the clinical application of CA in sepsis management.
