BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which...BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.展开更多
In this manuscript,we comment on the article,which explores the anti-cancer effects of Calculus bovis(CB)in tumor biology.We highlight its potential,particularly in hepatocellular carcinoma(HCC),where it inhibits the ...In this manuscript,we comment on the article,which explores the anti-cancer effects of Calculus bovis(CB)in tumor biology.We highlight its potential,particularly in hepatocellular carcinoma(HCC),where it inhibits the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways and induces apoptosis.CB contains compounds such as oleanolic acid and ursolic acid that target interleukin-6,mitogen-activated protein kinase 8,vascular endothelial growth factor,and caspase-3,offering anti-inflammatory and hepatoprotective benefits.The manuscript also discusses CB sativus(CBS),an artificial substitute,which has shown efficacy in reducing hepatic inflammation and oxidative stress in animal models.We emphasize the need for further research on the effects of CBS on the gut-liver axis and gut microbiota,and on targeting Wnt signaling and M2 tumor-associated macrophage as potential therapeutic strategies against HCC.展开更多
This editorial examines the therapeutic potential of traditional Chinese medicine(TCM)for aggressive cancers,particularly liver cancer.It highlights the study by Huang et al,which shows how Calculus bovis,a component ...This editorial examines the therapeutic potential of traditional Chinese medicine(TCM)for aggressive cancers,particularly liver cancer.It highlights the study by Huang et al,which shows how Calculus bovis,a component of the TCM Pien Tze Huang,suppresses liver cancer by inhibiting M2 macrophage polarization via the Wnt/β-catenin pathway.This research emphasizes the importance of transitioning from effective TCM formulations to isolating active components and understanding their mechanisms.While the study provides valuable insights,it primarily focuses on the Wnt/β-catenin pathway and does not delve deeply into the mechanisms of individual components.Future research should aim to comprehensively study these components,explore their interactions,and validate findings through clinical trials.This approach will integrate traditional wisdom with modern scientific validation,advancing the development of innovative cancer treatments based on TCM formulations.展开更多
Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies,liver cancer remains the fourth leading cause of cancer-related mortality...Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies,liver cancer remains the fourth leading cause of cancer-related mortality worldwide.Tumor relapse,resistance to current anti-cancer drugs,metastasis,and organ toxicity are the major challenges that prevent considerable improvements in patient survival and quality of life.Calculus bovis(CB),an ancient Chinese medicinal drug,has been used to treat various pathologies,including stroke,convulsion,epilepsy,pain,and cancer.In this editorial,we discuss the research findings recently published by Huang et al on the therapeutic effects of CB in inhibiting the development of liver cancer.Utilizing the comprehensive transcriptomic analyses,in vitro experiments,and in vivo studies,the authors demonstrated that CB treatment inhibits the tumor-promoting M2 phenotype of tumor-associated macrophages via downregulating Wnt pathway.While multiple studies have been performed to explore the molecular mechanisms regulated by CB,this study uniquely shows its role in modulating the M2 phenotype of macrophages present within the tumor microenvironment.This study opens new avenues of future investigations aimed at investigating this drug’s efficacy in various mouse models including the effects of combination therapy,and against drug-resistant tumors.展开更多
In the ongoing quest for new treatments in medicine,traditional Chinese medicine offers unique insights and potential.Recently,studies on the ability of Calculus bovis to inhibit M2-type tumour-associated macrophage p...In the ongoing quest for new treatments in medicine,traditional Chinese medicine offers unique insights and potential.Recently,studies on the ability of Calculus bovis to inhibit M2-type tumour-associated macrophage polarisation by modulating the Wnt/β-catenin signalling pathway to suppress liver cancer have undoubtedly revealed new benefits and hope for this field of research.The purpose of this article is to comment on this study and explore its strengths and weaknesses,thereby providing ideas for the future treatment of liver cancer.展开更多
Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are co...Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are considered as natural reservoir of M. bovis. However, in Burkina Faso, the circulation of these strains remains poorly understood and documented. This study aimed to identify and characterize Mycobacterium strains from suspected carcasses during routine meat inspection at Bobo-Dioulasso refrigerated slaughterhouse. A prospective cross-sectional study was conducted from January 2021 to December 2022 on cases of seizures linked to suspected bovine tuberculosis. Microbiological and molecular analyzes were used for mycobacterial strain isolation and characterization. Out of 50 samples, 24% tested positive by microscopy and 12% by culture. Molecular analysis identified 6 strains of Mycobacteria, exclusively Mycobacterium bovis specifically the subspecies bovis (Mycobacterium bovis subsp bovis). In conclusion, M. bovis subsp bovis is the primary agent responsible for bovine tuberculosis in Bobo-Dioulasso. Continuous monitoring of mycobacterial strains is therefore necessary for the effective control of this pathology in the local cattle population.展开更多
Intravesical bacillus Calmette-Guerin(BCG) instillation has been adopted for the treatment of patients with superficial bladder cancer. Severe adverse events due to local instillation of BCG are uncommon, with an over...Intravesical bacillus Calmette-Guerin(BCG) instillation has been adopted for the treatment of patients with superficial bladder cancer. Severe adverse events due to local instillation of BCG are uncommon, with an overall rate of serious complications of less than 5%. We report the case of an immunocompetent adult patient with multi-system effects, namely pneumonitis, granulomatous hepatitis and meningitis, who responded well to standard treatment for Mycobacterium bovis. This case highlights the importance of a thorough assessment of this type of patient.展开更多
The cellular immune response elicited by Mycobacterium bovis Bacille Calmette-Guérin (BCG) has been carefully investigated, but the humoral immune response has been partially neglected. BALB/c mice were immunized...The cellular immune response elicited by Mycobacterium bovis Bacille Calmette-Guérin (BCG) has been carefully investigated, but the humoral immune response has been partially neglected. BALB/c mice were immunized with BCG strain used to immunize humans. Anti-BCG antibodies, as assayed by ELISA, began to appear in the sera after the third week of immunization and plateaued three weeks after the 8th immunization. The total immunoglobulins (Igs) were purified by caprylic acid method from pooled serum collected after the 8th immunization. Anti-BCG antigen antibodies were detected in the total Igs preparation as well as in IgG, IgM, IgA, IgG1, IgG2a, and IgG2b, but not in the IgG3. Distinct BCG proteins were recognized the IgGs in Western blot analysis. Opsonization of BCG bacilli by the purified Igs potentiated internalization of the bacteria by murine Raw 264.7 macrophages. The intracellular BCG elimination coincided with the induction of NO production, which was more pronounced in cells infected with opsonized BCG compared to those infected with the non-opsonized bacteria. Coincidently, the production of NO was also higher in macrophages infected with opsonized BCG (maximal NO production at 48 h of incubation). The obtained results demonstrate that repeated inoculations of BCG effectively activate the humoral immune response, justifying the use of BCG as a live recombinant vaccine vector to insert genes encoding virulence factors controlled by antibodies.展开更多
In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in vivo.Through further in vitro studies,they s...In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in vivo.Through further in vitro studies,they showed that CB suppressed the M2 polarization of tumor-associated macrophages by suppressing the Wnt signaling pathway,which consequently inhibited the growth of liver cancer.Although the effects of traditional Chinese herbal medicine are often not scientifically proven,Huang et al successfully identified the molecular mechanism involved in the anticancer effect of CB,and it is anticipated that the molecular mechanisms involved in the effects of other traditional Chinese herbal medicines will be scientifically elucidated,as demonstrated in this article.展开更多
The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol consumption.This deter-mines great attention to the development and improvement of ...The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol consumption.This deter-mines great attention to the development and improvement of methods for early diagnosis and treatment of liver cancer.Huang et al presented a study in the World Journal of Gastroenterology,in which they showed that the use of the traditional Chinese medicine Calculus bovis(CB)can suppress tumor growth in mice by inhibiting M2 tumor-associated macrophages(TAM)through modulating the activity of the Wnt/β-catenin pathway.The interaction of CB components with the Wnt/β-catenin pathway,M2 TAM polarization,and tumor dynamics were studied using network pharmacology,transcriptomics,and molecular docking.It is now generally accepted that the polarization of TAM and the differentiation of the functions of M1 and M2 phagocytes are of great importance for the progression of neoplasms.It is assumed that M2 TAM promote proliferation and migration of tumor cells.Attempts to medicinally influence the Wnt/β-catenin pathway in order to modulate phagocyte polarization now belong to one of the most promising areas of immunotherapy of oncological diseases.Undoubtedly,the work of the Chinese authors deserves attention and further development.展开更多
To the Editor:Bovine tuberculosis (TB)is a zoonotic disease caused by Mycobacterium bovis.It not only seriously influences the raising of livestock but also threatens the health of human beings and other economically ...To the Editor:Bovine tuberculosis (TB)is a zoonotic disease caused by Mycobacterium bovis.It not only seriously influences the raising of livestock but also threatens the health of human beings and other economically important animals.Therefore, the prevention and control of M.boris has great significance for public and animal health.Spoligotyping is the most widely used method for genotyping of M.boris and investigates transmission across different geographical regions.However,its discriminatory power varies widely among countries.Variable number of tandem repeats (VNTR)analysis has emerged as an alternative method for genotyping of bacterial species isolates.展开更多
The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccina...The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccinated persons and individuals who are infected with mycobacteria but have not developed the disease. MPT64, an antigen secreted from actively growing Mycobacterium tuberculosis and some strains of M. bovis BCG such as BCG Tokyo and BCG Russia, is immunogenic and elicits delayed-type hypersensitivity (DTH) in guinea pigs and humans. This antigen has been used to develop a new skin test for the diagnosis of active TB infection. Two of the antigens encoded by the M. tuberculosis-specific region of difference 1 (RD1, deleted in M. bovis BCG strains), CFP10 (culture filtrate protein 10) and ESAT6 (early secreted antigenic target-6), also induce M. tuberculosis-specific DTH responses. The aim of this study was to investigate the DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo elicited by three purified recombinant proteins (rMPT64, rCFP10 and rESAT6) compared to those elicited by PPD. In this study genes encoding MPT64, CFP10, and ESAT6 were cloned and expressed as recombinant proteins with the addition of a C-terminal His6 tag for ease of purification by Immobilized Metal ion Affinity Chromatography (IMAC). The recombinant proteins (rMPT64, rCFP10, and rESAT6) were purified to homogeneity and were used to elicit DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo. The results showed that rMPT64 elicits a DTH response comparable to that of PPD in M. bovis BCG Tokyo-vaccinated animals. However, M. tuberculosis-infected animals show less reactivity to rMPT64 than they do to PPD. Although single rCFP10 or rESAT6 did not readily elicit a DTH response in M. tuberculosis-infected animals, combining these antigens with rMPT64 led to an increased DTH response, thus enabling the detection of TB infection.展开更多
目的牛分枝杆菌抗原MPB70、MPB83、CFP-10和ESAT-6的融合表达及相关特性分析。方法应用PCR方法从牛分枝杆菌临床分离株基因组中扩增获得mpb70、mpb83、cfp-10和esat-6四个目的基因片段。采用重叠延伸剪接技术(splicing by overlap exten...目的牛分枝杆菌抗原MPB70、MPB83、CFP-10和ESAT-6的融合表达及相关特性分析。方法应用PCR方法从牛分枝杆菌临床分离株基因组中扩增获得mpb70、mpb83、cfp-10和esat-6四个目的基因片段。采用重叠延伸剪接技术(splicing by overlap extension,SOE)获得融合基因cfp10-esat6和mpb83-cfp10-esat6,将mpb70和mpb83-cfp10-esat6串连于载体pUC19-Linker上,再将mpb70-mpb83-cfp10-esat6连于表达载体pET28a(+)中得到重组质粒pET70-83-C10-E6。转化BL21(DE3)感受态细胞后,经IPTG诱导获得以可溶形式表达的融合蛋白。用Ni2+亲合层析法纯化该融合蛋白。结果经ELISA验证该融合蛋白能分别与抗原蛋白MPB70、MPB83和CE(cfp10-esat6)的多抗反应,说明该融合蛋白具有四个抗原蛋白的免疫学活性。Western blot分析显示:该融合蛋白能与抗牛分枝杆菌阳性血清发生特异性反应,而与牛其它疾病的阳性血清不反应。热稳定性试验证明该融合蛋白属于热稳定性蛋白。结论融合表达了牛分枝杆菌的四种特异性抗原蛋白,该蛋白具有单个蛋白的免疫原性和稳定性,作为一种新型的诊断抗原具有良好的应用前景。展开更多
基金Supported by National Natural Science Foundation of China,No.82074450Education Department of Hunan Province,No.21A0243,No.21B0374,No.22B0397,and No.22B0392+2 种基金Research Project of"Academician Liu Liang Workstation"of Hunan University of Traditional Chinese Medicine,No.21YS003Hunan Administration of Traditional Chinese Medicine,No.B2023001 and No.B2023009Hunan Provincial Natural Science Foundation of China,No.2023JJ40481。
文摘BACKGROUND Calculus bovis(CB),used in traditional Chinese medicine,exhibits anti-tumor effects in various cancer models.It also constitutes an integral component of a compound formulation known as Pien Tze Huang,which is indicated for the treatment of liver cancer.However,its impact on the liver cancer tumor microenvironment,particularly on tumor-associated macrophages(TAMs),is not well understood.AIM To elucidate the anti-liver cancer effect of CB by inhibiting M2-TAM polarization via Wnt/β-catenin pathway modulation.METHODS This study identified the active components of CB using UPLC-Q-TOF-MS,evaluated its anti-neoplastic effects in a nude mouse model,and elucidated the underlying mechanisms via network pharmacology,transcriptomics,and molecular docking.In vitro assays were used to investigate the effects of CB-containing serum on HepG2 cells and M2-TAMs,and Wnt pathway modulation was validated by real-time reverse transcriptase-polymerase chain reaction and Western blot analysis.RESULTS This study identified 22 active components in CB,11 of which were detected in the bloodstream.Preclinical investigations have demonstrated the ability of CB to effectively inhibit liver tumor growth.An integrated approach employing network pharmacology,transcriptomics,and molecular docking implicated the Wnt signaling pathway as a target of the antineoplastic activity of CB by suppressing M2-TAM polarization.In vitro and in vivo experiments further confirmed that CB significantly hinders M2-TAM polarization and suppresses Wnt/β-catenin pathway activation.The inhibitory effect of CB on M2-TAMs was reversed when treated with the Wnt agonist SKL2001,confirming its pathway specificity.CONCLUSION This study demonstrated that CB mediates inhibition of M2-TAM polarization through the Wnt/β-catenin pathway,contributing to the suppression of liver cancer growth.
文摘In this manuscript,we comment on the article,which explores the anti-cancer effects of Calculus bovis(CB)in tumor biology.We highlight its potential,particularly in hepatocellular carcinoma(HCC),where it inhibits the phosphatidylinositol 3-kinase/protein kinase B/mammalian target of rapamycin pathways and induces apoptosis.CB contains compounds such as oleanolic acid and ursolic acid that target interleukin-6,mitogen-activated protein kinase 8,vascular endothelial growth factor,and caspase-3,offering anti-inflammatory and hepatoprotective benefits.The manuscript also discusses CB sativus(CBS),an artificial substitute,which has shown efficacy in reducing hepatic inflammation and oxidative stress in animal models.We emphasize the need for further research on the effects of CBS on the gut-liver axis and gut microbiota,and on targeting Wnt signaling and M2 tumor-associated macrophage as potential therapeutic strategies against HCC.
基金Supported by National Natural Science Foundation of China,No.82204909.
文摘This editorial examines the therapeutic potential of traditional Chinese medicine(TCM)for aggressive cancers,particularly liver cancer.It highlights the study by Huang et al,which shows how Calculus bovis,a component of the TCM Pien Tze Huang,suppresses liver cancer by inhibiting M2 macrophage polarization via the Wnt/β-catenin pathway.This research emphasizes the importance of transitioning from effective TCM formulations to isolating active components and understanding their mechanisms.While the study provides valuable insights,it primarily focuses on the Wnt/β-catenin pathway and does not delve deeply into the mechanisms of individual components.Future research should aim to comprehensively study these components,explore their interactions,and validate findings through clinical trials.This approach will integrate traditional wisdom with modern scientific validation,advancing the development of innovative cancer treatments based on TCM formulations.
基金Supported by the National Institutes of Health grants,No.K99HL146954 and No.R00HL146954the UTHSC College of Pharmacy Research Seed Grant award,No.2023.
文摘Despite significant advances in our understanding of the molecular pathogenesis of liver cancer and the availability of novel pharmacotherapies,liver cancer remains the fourth leading cause of cancer-related mortality worldwide.Tumor relapse,resistance to current anti-cancer drugs,metastasis,and organ toxicity are the major challenges that prevent considerable improvements in patient survival and quality of life.Calculus bovis(CB),an ancient Chinese medicinal drug,has been used to treat various pathologies,including stroke,convulsion,epilepsy,pain,and cancer.In this editorial,we discuss the research findings recently published by Huang et al on the therapeutic effects of CB in inhibiting the development of liver cancer.Utilizing the comprehensive transcriptomic analyses,in vitro experiments,and in vivo studies,the authors demonstrated that CB treatment inhibits the tumor-promoting M2 phenotype of tumor-associated macrophages via downregulating Wnt pathway.While multiple studies have been performed to explore the molecular mechanisms regulated by CB,this study uniquely shows its role in modulating the M2 phenotype of macrophages present within the tumor microenvironment.This study opens new avenues of future investigations aimed at investigating this drug’s efficacy in various mouse models including the effects of combination therapy,and against drug-resistant tumors.
文摘In the ongoing quest for new treatments in medicine,traditional Chinese medicine offers unique insights and potential.Recently,studies on the ability of Calculus bovis to inhibit M2-type tumour-associated macrophage polarisation by modulating the Wnt/β-catenin signalling pathway to suppress liver cancer have undoubtedly revealed new benefits and hope for this field of research.The purpose of this article is to comment on this study and explore its strengths and weaknesses,thereby providing ideas for the future treatment of liver cancer.
文摘Bovine tuberculosis (bTB) is an endemic zoonosis significantly affects animal health in Burkina Faso. The primary causative agent is Mycobacterium tuberculosis (M. tuberculosis) complex, mainly M. bovis. Cattle are considered as natural reservoir of M. bovis. However, in Burkina Faso, the circulation of these strains remains poorly understood and documented. This study aimed to identify and characterize Mycobacterium strains from suspected carcasses during routine meat inspection at Bobo-Dioulasso refrigerated slaughterhouse. A prospective cross-sectional study was conducted from January 2021 to December 2022 on cases of seizures linked to suspected bovine tuberculosis. Microbiological and molecular analyzes were used for mycobacterial strain isolation and characterization. Out of 50 samples, 24% tested positive by microscopy and 12% by culture. Molecular analysis identified 6 strains of Mycobacteria, exclusively Mycobacterium bovis specifically the subspecies bovis (Mycobacterium bovis subsp bovis). In conclusion, M. bovis subsp bovis is the primary agent responsible for bovine tuberculosis in Bobo-Dioulasso. Continuous monitoring of mycobacterial strains is therefore necessary for the effective control of this pathology in the local cattle population.
文摘Intravesical bacillus Calmette-Guerin(BCG) instillation has been adopted for the treatment of patients with superficial bladder cancer. Severe adverse events due to local instillation of BCG are uncommon, with an overall rate of serious complications of less than 5%. We report the case of an immunocompetent adult patient with multi-system effects, namely pneumonitis, granulomatous hepatitis and meningitis, who responded well to standard treatment for Mycobacterium bovis. This case highlights the importance of a thorough assessment of this type of patient.
文摘The cellular immune response elicited by Mycobacterium bovis Bacille Calmette-Guérin (BCG) has been carefully investigated, but the humoral immune response has been partially neglected. BALB/c mice were immunized with BCG strain used to immunize humans. Anti-BCG antibodies, as assayed by ELISA, began to appear in the sera after the third week of immunization and plateaued three weeks after the 8th immunization. The total immunoglobulins (Igs) were purified by caprylic acid method from pooled serum collected after the 8th immunization. Anti-BCG antigen antibodies were detected in the total Igs preparation as well as in IgG, IgM, IgA, IgG1, IgG2a, and IgG2b, but not in the IgG3. Distinct BCG proteins were recognized the IgGs in Western blot analysis. Opsonization of BCG bacilli by the purified Igs potentiated internalization of the bacteria by murine Raw 264.7 macrophages. The intracellular BCG elimination coincided with the induction of NO production, which was more pronounced in cells infected with opsonized BCG compared to those infected with the non-opsonized bacteria. Coincidently, the production of NO was also higher in macrophages infected with opsonized BCG (maximal NO production at 48 h of incubation). The obtained results demonstrate that repeated inoculations of BCG effectively activate the humoral immune response, justifying the use of BCG as a live recombinant vaccine vector to insert genes encoding virulence factors controlled by antibodies.
基金Supported by Japan Society for the Promotion of Science,No.23K07347。
文摘In this issue of World Journal of Gastroenterology,Huang et al reported that Calculus bovis(CB),a traditional Chinese herbal medicine,impedes the growth of liver cancers in vivo.Through further in vitro studies,they showed that CB suppressed the M2 polarization of tumor-associated macrophages by suppressing the Wnt signaling pathway,which consequently inhibited the growth of liver cancer.Although the effects of traditional Chinese herbal medicine are often not scientifically proven,Huang et al successfully identified the molecular mechanism involved in the anticancer effect of CB,and it is anticipated that the molecular mechanisms involved in the effects of other traditional Chinese herbal medicines will be scientifically elucidated,as demonstrated in this article.
文摘The problem of liver cancer is becoming increasingly important due to the epi-demic of metabolic diseases and persistent high alcohol consumption.This deter-mines great attention to the development and improvement of methods for early diagnosis and treatment of liver cancer.Huang et al presented a study in the World Journal of Gastroenterology,in which they showed that the use of the traditional Chinese medicine Calculus bovis(CB)can suppress tumor growth in mice by inhibiting M2 tumor-associated macrophages(TAM)through modulating the activity of the Wnt/β-catenin pathway.The interaction of CB components with the Wnt/β-catenin pathway,M2 TAM polarization,and tumor dynamics were studied using network pharmacology,transcriptomics,and molecular docking.It is now generally accepted that the polarization of TAM and the differentiation of the functions of M1 and M2 phagocytes are of great importance for the progression of neoplasms.It is assumed that M2 TAM promote proliferation and migration of tumor cells.Attempts to medicinally influence the Wnt/β-catenin pathway in order to modulate phagocyte polarization now belong to one of the most promising areas of immunotherapy of oncological diseases.Undoubtedly,the work of the Chinese authors deserves attention and further development.
文摘To the Editor:Bovine tuberculosis (TB)is a zoonotic disease caused by Mycobacterium bovis.It not only seriously influences the raising of livestock but also threatens the health of human beings and other economically important animals.Therefore, the prevention and control of M.boris has great significance for public and animal health.Spoligotyping is the most widely used method for genotyping of M.boris and investigates transmission across different geographical regions.However,its discriminatory power varies widely among countries.Variable number of tandem repeats (VNTR)analysis has emerged as an alternative method for genotyping of bacterial species isolates.
文摘The tuberculin Purified Protein Derivative (PPD) skin test is widely used;however, the results are often inaccurate. Positive results can be observed in patients with active tuberculosis (TB) as well as in BCG-vaccinated persons and individuals who are infected with mycobacteria but have not developed the disease. MPT64, an antigen secreted from actively growing Mycobacterium tuberculosis and some strains of M. bovis BCG such as BCG Tokyo and BCG Russia, is immunogenic and elicits delayed-type hypersensitivity (DTH) in guinea pigs and humans. This antigen has been used to develop a new skin test for the diagnosis of active TB infection. Two of the antigens encoded by the M. tuberculosis-specific region of difference 1 (RD1, deleted in M. bovis BCG strains), CFP10 (culture filtrate protein 10) and ESAT6 (early secreted antigenic target-6), also induce M. tuberculosis-specific DTH responses. The aim of this study was to investigate the DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo elicited by three purified recombinant proteins (rMPT64, rCFP10 and rESAT6) compared to those elicited by PPD. In this study genes encoding MPT64, CFP10, and ESAT6 were cloned and expressed as recombinant proteins with the addition of a C-terminal His6 tag for ease of purification by Immobilized Metal ion Affinity Chromatography (IMAC). The recombinant proteins (rMPT64, rCFP10, and rESAT6) were purified to homogeneity and were used to elicit DTH responses in guinea pigs infected with M. tuberculosis or M. bovis BCG Tokyo. The results showed that rMPT64 elicits a DTH response comparable to that of PPD in M. bovis BCG Tokyo-vaccinated animals. However, M. tuberculosis-infected animals show less reactivity to rMPT64 than they do to PPD. Although single rCFP10 or rESAT6 did not readily elicit a DTH response in M. tuberculosis-infected animals, combining these antigens with rMPT64 led to an increased DTH response, thus enabling the detection of TB infection.
文摘目的牛分枝杆菌抗原MPB70、MPB83、CFP-10和ESAT-6的融合表达及相关特性分析。方法应用PCR方法从牛分枝杆菌临床分离株基因组中扩增获得mpb70、mpb83、cfp-10和esat-6四个目的基因片段。采用重叠延伸剪接技术(splicing by overlap extension,SOE)获得融合基因cfp10-esat6和mpb83-cfp10-esat6,将mpb70和mpb83-cfp10-esat6串连于载体pUC19-Linker上,再将mpb70-mpb83-cfp10-esat6连于表达载体pET28a(+)中得到重组质粒pET70-83-C10-E6。转化BL21(DE3)感受态细胞后,经IPTG诱导获得以可溶形式表达的融合蛋白。用Ni2+亲合层析法纯化该融合蛋白。结果经ELISA验证该融合蛋白能分别与抗原蛋白MPB70、MPB83和CE(cfp10-esat6)的多抗反应,说明该融合蛋白具有四个抗原蛋白的免疫学活性。Western blot分析显示:该融合蛋白能与抗牛分枝杆菌阳性血清发生特异性反应,而与牛其它疾病的阳性血清不反应。热稳定性试验证明该融合蛋白属于热稳定性蛋白。结论融合表达了牛分枝杆菌的四种特异性抗原蛋白,该蛋白具有单个蛋白的免疫原性和稳定性,作为一种新型的诊断抗原具有良好的应用前景。
