Mycobacterium tuberculosis is able to establish a chronic colonization of lung macrophages in a c... more Mycobacterium tuberculosis is able to establish a chronic colonization of lung macrophages in a controlled replication manner, giving rise to a so-called latent infection. Conversely, when intracellular bacteria undergo actively uncontrolled replication rates, they provide the switch for the active infection called tuberculosis to occur. Our group found that the pathogen is able to manipulate the activity of endolysosomal enzymes, cathepsins, directly at the level of gene expression or indirectly by regulating their natural inhibitors, cystatins. To provide evidence for the crucial role of cathepsin manipulation for the success of tuberculosis bacilli in their intracellular survival, we used liposomal delivery of saquinavir. This protease inhibitor was previously found to be able to increase cathepsin proteolytic activity, overcoming the pathogen induced blockade. In this study, we demonstrate that incorporation in liposomes was able to increase the efficiency of saquinavir internal...
Despite the available antibiotics, tuberculosis (TB) has made its return since the 90’s of the la... more Despite the available antibiotics, tuberculosis (TB) has made its return since the 90’s of the last century as a global threat mostly due to co-infection with HIV, to the emergence of drug resistant strains and the lack of an effective vaccine. Host-directed strategies could be exploited to improve treatment efficacy, contain drug-resistant strains, improve immune responses and reduce disease severity. Macrophages in the lungs are often found infected with Mycobacterium tuberculosis (Mtb) and/or with HIV. The long-term survival of lung macrophages infected with Mtb or with HIV, together with their ability to produce viral particles, especially during TB, makes these niches major contributors to the pathogenicity of the infection. Among the available drugs to control HIV infection, protease inhibitors (PIs), acting at post-integrational stages of virus replication cycle, are the only drugs able to interfere with virus production and release from macrophages during chronic infection. ...
Tuberculosis owes its resurgence as a major global health threat mostly to the emergence of drug ... more Tuberculosis owes its resurgence as a major global health threat mostly to the emergence of drug resistance and coinfection with HIV. The synergy between HIV andMycobacterium tuberculosis(Mtb) modifies the host immune environment to enhance both viral and bacterial replication and spread. In the lung immune context, both pathogens infect macrophages, establishing favorable intracellular niches. Both manipulate the endocytic pathway in order to avoid destruction. Relevant players of the endocytic pathway to control pathogens include endolysosomal proteases, cathepsins, and their natural inhibitors, cystatins. Here, a mapping of the human macrophage transcriptome for type I and II cystatins during Mtb, HIV, or Mtb-HIV infection displayed different profiles of gene expression, revealing cystatin C as a potential target to control mycobacterial infection as well as HIV coinfection. We found that cystatin C silencing in macrophages significantly improves the intracellular killing of Mtb,...
Propolis which is a natural resinous product from the honeybees, is becoming increasingly popular... more Propolis which is a natural resinous product from the honeybees, is becoming increasingly popular for its diverse therapeutic and industrial applications. In this study, we report for the first time the antioxidant, cytotoxic, and antinociceptive activities of propolis from Bangladesh (BDP). The antioxidant activities were measured by biochemical analyses while cytotoxicity was evaluated by brine shrimp lethality bioassay. Analgesic activity was evaluated by tail immersion and acetic acid-induced writhing models in mice. BDP contained higher concentrations of polyphenols, flavonoids, tannins, ascorbic acid, vitamin E, and reducing sugars, as compared to previous reports of propolis from several countries. BDP also exhibited higher free radical-scavenging activities and a dose-dependent reducing power activity indicating its superior antioxidant potential. Moreover, BDP extract was most toxic to brine shrimp nauplii, with 50% lethal concentration (LC 50) of 57.99 µg/mL and exhibited considerable antinociceptive activities which may be mediated via central and peripheral inhibitory mechanisms. Practical applications BDP is a honeybee product, becoming increasingly popular due its potential contributions to human health. BDP is a rich source of natural antioxidants which has the potential to be used to ameliorate oxidative stress disorders and has useful antinociceptive activities. It may be useful as potential therapeutic agents against cancer, pesticidal agents, and for other cytotoxic uses.
Mycobacterium tuberculosis is able to establish a chronic colonization of lung macrophages in a c... more Mycobacterium tuberculosis is able to establish a chronic colonization of lung macrophages in a controlled replication manner, giving rise to a so-called latent infection. Conversely, when intracellular bacteria undergo actively uncontrolled replication rates, they provide the switch for the active infection called tuberculosis to occur. Our group found that the pathogen is able to manipulate the activity of endolysosomal enzymes, cathepsins, directly at the level of gene expression or indirectly by regulating their natural inhibitors, cystatins. To provide evidence for the crucial role of cathepsin manipulation for the success of tuberculosis bacilli in their intracellular survival, we used liposomal delivery of saquinavir. This protease inhibitor was previously found to be able to increase cathepsin proteolytic activity, overcoming the pathogen induced blockade. In this study, we demonstrate that incorporation in liposomes was able to increase the efficiency of saquinavir internal...
Despite the available antibiotics, tuberculosis (TB) has made its return since the 90’s of the la... more Despite the available antibiotics, tuberculosis (TB) has made its return since the 90’s of the last century as a global threat mostly due to co-infection with HIV, to the emergence of drug resistant strains and the lack of an effective vaccine. Host-directed strategies could be exploited to improve treatment efficacy, contain drug-resistant strains, improve immune responses and reduce disease severity. Macrophages in the lungs are often found infected with Mycobacterium tuberculosis (Mtb) and/or with HIV. The long-term survival of lung macrophages infected with Mtb or with HIV, together with their ability to produce viral particles, especially during TB, makes these niches major contributors to the pathogenicity of the infection. Among the available drugs to control HIV infection, protease inhibitors (PIs), acting at post-integrational stages of virus replication cycle, are the only drugs able to interfere with virus production and release from macrophages during chronic infection. ...
Tuberculosis owes its resurgence as a major global health threat mostly to the emergence of drug ... more Tuberculosis owes its resurgence as a major global health threat mostly to the emergence of drug resistance and coinfection with HIV. The synergy between HIV andMycobacterium tuberculosis(Mtb) modifies the host immune environment to enhance both viral and bacterial replication and spread. In the lung immune context, both pathogens infect macrophages, establishing favorable intracellular niches. Both manipulate the endocytic pathway in order to avoid destruction. Relevant players of the endocytic pathway to control pathogens include endolysosomal proteases, cathepsins, and their natural inhibitors, cystatins. Here, a mapping of the human macrophage transcriptome for type I and II cystatins during Mtb, HIV, or Mtb-HIV infection displayed different profiles of gene expression, revealing cystatin C as a potential target to control mycobacterial infection as well as HIV coinfection. We found that cystatin C silencing in macrophages significantly improves the intracellular killing of Mtb,...
Propolis which is a natural resinous product from the honeybees, is becoming increasingly popular... more Propolis which is a natural resinous product from the honeybees, is becoming increasingly popular for its diverse therapeutic and industrial applications. In this study, we report for the first time the antioxidant, cytotoxic, and antinociceptive activities of propolis from Bangladesh (BDP). The antioxidant activities were measured by biochemical analyses while cytotoxicity was evaluated by brine shrimp lethality bioassay. Analgesic activity was evaluated by tail immersion and acetic acid-induced writhing models in mice. BDP contained higher concentrations of polyphenols, flavonoids, tannins, ascorbic acid, vitamin E, and reducing sugars, as compared to previous reports of propolis from several countries. BDP also exhibited higher free radical-scavenging activities and a dose-dependent reducing power activity indicating its superior antioxidant potential. Moreover, BDP extract was most toxic to brine shrimp nauplii, with 50% lethal concentration (LC 50) of 57.99 µg/mL and exhibited considerable antinociceptive activities which may be mediated via central and peripheral inhibitory mechanisms. Practical applications BDP is a honeybee product, becoming increasingly popular due its potential contributions to human health. BDP is a rich source of natural antioxidants which has the potential to be used to ameliorate oxidative stress disorders and has useful antinociceptive activities. It may be useful as potential therapeutic agents against cancer, pesticidal agents, and for other cytotoxic uses.
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Papers by Manoj Mandal