Xiugong Gao - Academia.edu (original) (raw)
Papers by Xiugong Gao
Stem Cell Research & Therapy
Background Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs)... more Background Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) hold great promise in toxicological applications as well as in regenerative medicine. Previous efforts on hepatocyte differentiation have mostly relied on the use of growth factors (GFs) to recapitulate developmental signals under in vitro conditions. Recently, the use of small molecules (SMs) has emerged as an attractive tool to induce cell fate transition due to its superiority in terms of both quality and cost. However, HLCs derived using SMs have not been well characterized, especially on the transcriptome level. Methods HLCs were differentiated from human iPSCs using a protocol that only involves SMs and characterized by transcriptomic analysis using whole genome microarrays. Results HLCs derived using the SM protocol (HLC_SM) displayed specific hepatic marker expression and demonstrated key hepatic functions. Transcriptomic analysis of the SM-driven differentiation defined a hepat...
Cell Biology and Toxicology
Regulatory Toxicology and Pharmacology
Journal of Nanobiotechnology
Background: The widespread application of silver nanoparticles (AgNPs) and silver-containing prod... more Background: The widespread application of silver nanoparticles (AgNPs) and silver-containing products has raised public safety concerns about their adverse effects on human health and the environment. To date, in vitro toxic effects of AgNPs and ionic silver (Ag + ) on many somatic cell types are well established. However, no studies have been conducted hitherto to evaluate their effect on cellular transcriptome in embryonic stem cells (ESCs).
Cell biology and toxicology, Jan 31, 2017
Hepatocytes derived from human induced pluripotent stem cells (iPSCs) hold great promise as an in... more Hepatocytes derived from human induced pluripotent stem cells (iPSCs) hold great promise as an in vitro liver model by virtue of their unlimited long-term supply, stability and consistency in functionality, and affordability of donor diversity. However, the suitability of iPSC-derived hepatocytes (iPSC-Heps) for toxicology studies has not been fully validated. In the current study, we characterized global gene expression profiles of iPSC-Heps in comparison to those of primary human hepatocytes (PHHs) and several human hepatoma cell lines (HepaRG, HuH-7, HepG2, and HepG2/C3A). Furthermore, genes associated with hepatotoxicity, drug-metabolizing enzymes, transporters, and nuclear receptors were extracted for more detailed comparisons. Our results showed that iPSC-Heps correlate more closely to PHHs than hepatoma cell lines, suggesting that iPSC-Heps had a relatively mature hepatic phenotype that more closely resembles that of adult hepatocytes. HepaRG was the sole exception but noneth...
The Faseb Journal, Mar 1, 2006
Background: Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a signif... more Background: Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE) cells and bronchial/tracheal epithelial (BTE) cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF), and expression of inducible nitric oxide synthase (iNOS) were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant.
Toxicology and Applied Pharmacology, 2015
Developmental toxicity testing has traditionally relied on animal models which are costly, time c... more Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72h after exposure to 0.25mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment.
Journal of Applied Toxicology, 2015
The increased use of silver nanoparticles (AgNPs) in foods and cosmetics has raised public safety... more The increased use of silver nanoparticles (AgNPs) in foods and cosmetics has raised public safety concerns. However, only limited knowledge exists on the effect of AgNPs on the cellular transcriptome. This study evaluated global gene expression profiles of human liver HepG2 cells exposed to 20 and 50 nm AgNPs for 4 and 24 h at 2.5 µg ml(-1) . Exposure to 20 nm AgNPs resulted in 811 altered genes after 4 h, but much less after 24 h. Exposure to 50 nm AgNPs showed minimal altered genes at both exposure times. The HepG2 cells responded to the toxic insult of AgNPs by transiently upregulating stress response genes such as metallothioneins and heat shock proteins. Functional analysis of the altered genes showed more than 20 major biological processes were affected, of which metabolism, development, cell differentiation and cell death were the most dominant categories. Several cellular pathways were also impacted by AgNP exposure, including the p53 signaling pathway and the NRF2-mediated oxidative stress response pathway, which may lead to increased oxidative stress and DNA damage in the cell and potentially result in genotoxicity and carcinogenicity. Together, these results indicate that HepG2 cells underwent a multitude of cellular processes in response to the toxic insult of AgNP exposure, and suggest that toxicogenomic characterization of human HepG2 cells could serve as an alternative model for assessing toxicities of NPs.
Toxicology Reports, 2015
Male and female rats (26-day-old) were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acet... more Male and female rats (26-day-old) were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acetate (AgAc) in drinking water for 10 weeks prior to and during mating. Spermpositive females remained within their dose groups and were exposed to silver acetate during gestation and lactation. At postnatal day 26, the effect of silver ions on the developing F1 generation rat thymus was evaluated at the transcriptional level using whole-genome microarrays. Gene expression profiling analyses identified a dozen differentially expressed genes (DEGs) in each dose group using a loose criterion of fold change (FC) >1.5 and unadjusted p < 0.05, regardless of whether the analysis was conducted within each gender group or with both gender groups combined. No dose-dependent effect was observed on the number of DEGs. In addition, none of these genes had a false discovery rate (FDR) <0.05 after correction for multiple testing. These results in combination with the observation that thymus-to-body-weight ratios were not affected and no histopathological abnormalities were identified indicate that in utero exposure to silver ions up to 26.0 mg/kg (equivalent to 40.0 mg/kg silver acetate) did not have an adverse effect on the developing thymus.
PloS one, 2014
The Tox21 program calls for transforming toxicology testing from traditional in vivo tests to les... more The Tox21 program calls for transforming toxicology testing from traditional in vivo tests to less expensive and higher throughput in vitro methods. In developmental toxicology, a spectrum of alternative methods including cell line based tests has been developed. In particular, embryonic stem cells (ESCs) have received widespread attention as a promising alternative model for developmental toxicity assessment. Here, we characterized gene expression changes during mouse ESC differentiation and their modulation by developmental toxicants. C57BL/6 ESCs were allowed to differentiate spontaneously and RNA of vehicle controls was collected at 0, 24, 48, 72, 96, 120 and 168 h after embryoid body (EB) formation; RNA of compound-exposed EBs were collected at 24 h. Samples were hybridized to Affymetrix Mouse Gene 2.0 ST Array; using stringent cut-off criteria of Bonferroni-adjusted p<0.05 and fold change >2.0, a total of 1996 genes were found differentially expressed among the vehicle c...
Wei sheng wu xue bao = Acta microbiologica Sinica, 1998
A lipase-producing bacterium strain was isolated from soil and was identified as Pseudomonas sp..... more A lipase-producing bacterium strain was isolated from soil and was identified as Pseudomonas sp.. Its lipase yield was improved 2.25-fold by combined treatment of UV irradiation and NTG. The lipase fermentation condition for the mutant strain was optimized with Plackett-Burman design and Response Surface Analysis (RSA), and the formula of the optimum medium suitable for industrial scale fermentation was thereby established. A maximum yield of 87.5 U/ml was obtained.
Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica, 1997
The asymmetric esterification of octanoic acid with racemic 2-octanol catalyzed by a lipase from ... more The asymmetric esterification of octanoic acid with racemic 2-octanol catalyzed by a lipase from Pseudomonas sp. was investigated in several typical solvents. It was found that the catalytic activity and the enantioselectivity of the enzyme were governed by different physicochemical parameters of the solvent employed. While the former depended on the hydrophobicity (lgP) of the solvent, by contrast the latter was a function of the dielectric constant and the dipole moment. A mechanistic model for the binding site of the enzyme was postulated to rationalize this phenomenon based on the results of the kinetic studies of the reaction in some representative solvents.
The Biochemical journal, Jan 15, 1998
The reactivation of the homodimeric triosephosphate isomerases (TIMs) from Trypanosoma brucei, T.... more The reactivation of the homodimeric triosephosphate isomerases (TIMs) from Trypanosoma brucei, T. cruzi, Leishmania mexicana and humans was determined after their denaturation with guanidine hydrochloride. In the range of 2-32 microg of T. brucei TIM per ml and 0.2-5 microg of the other enzymes per ml, the rate and extent of TIM reactivation depended on protein concentration, indicating that at these protein concentrations, the rate-limiting step of reactivation is monomer association and not monomer folding. The rate of monomer association was more than one order of magnitude lower in the T. brucei enzyme than in the other three enzymes. Suramin is a drug of choice in the treatment of sleeping sickness, but its mechanism of action is not known. At micromolar concentrations, Suramin inhibited the reactivation of the four enzymes, but the extent of inhibition by Suramin decreased with increasing protein concentration as consequence of a diminution of the life time of the folded monom...
Biomarkers in medicine, 2010
Biomarkers play a pivotal role in the early detection and diagnosis of cancer. Accurate quantitat... more Biomarkers play a pivotal role in the early detection and diagnosis of cancer. Accurate quantitation of certain biomarkers is crucial to reach correct treatment decisions. In practice, immunohistochemistry (IHC) remains the most important diagnostic technique to evaluate protein biomarker expression in tissue biopsies. However, IHC has largely been qualitative. Low specificity of the mammalian IgG antibodies used to capture the analytes and instability of fluorescence from the organic dyes used as the detecting agents are among the major factors that have impeded the development of quantitative IHC. Avian IgY antibodies have many attractive biochemical, immunological and production advantages over IgGs and are, therefore, better substitutes in diagnostic applications. Using IgY in immunoassays can potentially eliminate false positives and often results in low background and interference. Quantum dots (QDs) have recently emerged as a novel class of fluorophores, promising for many bi...
Recent Advances in Nanotechnology, 2011
International journal of toxicology, Jul 6, 2014
Mustard gas (sulfur mustard [SM], bis-[2-chloroethyl] sulfide) is a vesicating chemical warfare a... more Mustard gas (sulfur mustard [SM], bis-[2-chloroethyl] sulfide) is a vesicating chemical warfare agent and a potential chemical terrorism agent. Exposure of SM causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract; of these, the respiratory injury, if severe, may even be fatal. Therefore, developing an effective therapeutic strategy to protect against SM-induced respiratory injury is an urgent priority of not only the US military but also the civilian antiterrorism agencies, for example, the Homeland Security. Toward developing a respiratory medical countermeasure for SM, four different classes of therapeutic compounds have been evaluated in the past: anti-inflammatory compounds, antioxidants, protease inhibitors and antiapoptotic compounds. This review examines all of these different options; however, it suggests that preventing cell death by inhibiting apoptosis seems to be a compelling strategy but possibly dependent on adjunct therapies u...
Stem Cell Research & Therapy
Background Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs)... more Background Hepatocyte-like cells (HLCs) derived from human induced pluripotent stem cells (iPSCs) hold great promise in toxicological applications as well as in regenerative medicine. Previous efforts on hepatocyte differentiation have mostly relied on the use of growth factors (GFs) to recapitulate developmental signals under in vitro conditions. Recently, the use of small molecules (SMs) has emerged as an attractive tool to induce cell fate transition due to its superiority in terms of both quality and cost. However, HLCs derived using SMs have not been well characterized, especially on the transcriptome level. Methods HLCs were differentiated from human iPSCs using a protocol that only involves SMs and characterized by transcriptomic analysis using whole genome microarrays. Results HLCs derived using the SM protocol (HLC_SM) displayed specific hepatic marker expression and demonstrated key hepatic functions. Transcriptomic analysis of the SM-driven differentiation defined a hepat...
Cell Biology and Toxicology
Regulatory Toxicology and Pharmacology
Journal of Nanobiotechnology
Background: The widespread application of silver nanoparticles (AgNPs) and silver-containing prod... more Background: The widespread application of silver nanoparticles (AgNPs) and silver-containing products has raised public safety concerns about their adverse effects on human health and the environment. To date, in vitro toxic effects of AgNPs and ionic silver (Ag + ) on many somatic cell types are well established. However, no studies have been conducted hitherto to evaluate their effect on cellular transcriptome in embryonic stem cells (ESCs).
Cell biology and toxicology, Jan 31, 2017
Hepatocytes derived from human induced pluripotent stem cells (iPSCs) hold great promise as an in... more Hepatocytes derived from human induced pluripotent stem cells (iPSCs) hold great promise as an in vitro liver model by virtue of their unlimited long-term supply, stability and consistency in functionality, and affordability of donor diversity. However, the suitability of iPSC-derived hepatocytes (iPSC-Heps) for toxicology studies has not been fully validated. In the current study, we characterized global gene expression profiles of iPSC-Heps in comparison to those of primary human hepatocytes (PHHs) and several human hepatoma cell lines (HepaRG, HuH-7, HepG2, and HepG2/C3A). Furthermore, genes associated with hepatotoxicity, drug-metabolizing enzymes, transporters, and nuclear receptors were extracted for more detailed comparisons. Our results showed that iPSC-Heps correlate more closely to PHHs than hepatoma cell lines, suggesting that iPSC-Heps had a relatively mature hepatic phenotype that more closely resembles that of adult hepatocytes. HepaRG was the sole exception but noneth...
The Faseb Journal, Mar 1, 2006
Background: Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a signif... more Background: Sulfur mustard (SM) is a potent chemical vesicant warfare agent that remains a significant military and civilian threat. Inhalation of SM gas causes airway inflammation and injury. In recent years, there has been increasing evidence of the effectiveness of macrolide antibiotics in treating chronic airway inflammatory diseases. In this study, the anti-cytotoxic and anti-inflammatory effects of a representative macrolide antibiotic, roxithromycin, were tested in vitro using SM-exposed normal human small airway epithelial (SAE) cells and bronchial/tracheal epithelial (BTE) cells. Cell viability, expression of proinflammatory cytokines including interleukin (IL)-1β, IL-6, IL-8 and tumor necrosis factor (TNF), and expression of inducible nitric oxide synthase (iNOS) were examined, since these proinflammatory cytokines/mediators are import indicators of tissue inflammatory responses. We suggest that the influence of roxithromycin on SM-induced inflammatory reaction could play an important therapeutic role in the cytotoxicity exerted by this toxicant.
Toxicology and Applied Pharmacology, 2015
Developmental toxicity testing has traditionally relied on animal models which are costly, time c... more Developmental toxicity testing has traditionally relied on animal models which are costly, time consuming, and require the sacrifice of large numbers of animals. In addition, there are significant disparities between human beings and animals in their responses to chemicals. Thalidomide is a species-specific developmental toxicant that causes severe limb malformations in humans but not in mice. Here, we used microarrays to study transcriptomic changes induced by thalidomide in an in vitro model based on differentiation of mouse embryonic stem cells (mESCs). C57BL/6 mESCs were allowed to differentiate spontaneously and RNA was collected at 24, 48, and 72h after exposure to 0.25mM thalidomide. Global gene expression analysis using microarrays revealed hundreds of differentially expressed genes upon thalidomide exposure that were enriched in gene ontology (GO) terms and canonical pathways associated with embryonic development and differentiation. In addition, many genes were found to be involved in small GTPases-mediated signal transduction, heart development, and inflammatory responses, which coincide with clinical evidences and may represent critical embryotoxicities of thalidomide. These results demonstrate that transcriptomics in combination with mouse embryonic stem cell differentiation is a promising alternative model for developmental toxicity assessment.
Journal of Applied Toxicology, 2015
The increased use of silver nanoparticles (AgNPs) in foods and cosmetics has raised public safety... more The increased use of silver nanoparticles (AgNPs) in foods and cosmetics has raised public safety concerns. However, only limited knowledge exists on the effect of AgNPs on the cellular transcriptome. This study evaluated global gene expression profiles of human liver HepG2 cells exposed to 20 and 50 nm AgNPs for 4 and 24 h at 2.5 µg ml(-1) . Exposure to 20 nm AgNPs resulted in 811 altered genes after 4 h, but much less after 24 h. Exposure to 50 nm AgNPs showed minimal altered genes at both exposure times. The HepG2 cells responded to the toxic insult of AgNPs by transiently upregulating stress response genes such as metallothioneins and heat shock proteins. Functional analysis of the altered genes showed more than 20 major biological processes were affected, of which metabolism, development, cell differentiation and cell death were the most dominant categories. Several cellular pathways were also impacted by AgNP exposure, including the p53 signaling pathway and the NRF2-mediated oxidative stress response pathway, which may lead to increased oxidative stress and DNA damage in the cell and potentially result in genotoxicity and carcinogenicity. Together, these results indicate that HepG2 cells underwent a multitude of cellular processes in response to the toxic insult of AgNP exposure, and suggest that toxicogenomic characterization of human HepG2 cells could serve as an alternative model for assessing toxicities of NPs.
Toxicology Reports, 2015
Male and female rats (26-day-old) were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acet... more Male and female rats (26-day-old) were exposed to 0.0, 0.4, 4 or 40 mg/kg body weight silver acetate (AgAc) in drinking water for 10 weeks prior to and during mating. Spermpositive females remained within their dose groups and were exposed to silver acetate during gestation and lactation. At postnatal day 26, the effect of silver ions on the developing F1 generation rat thymus was evaluated at the transcriptional level using whole-genome microarrays. Gene expression profiling analyses identified a dozen differentially expressed genes (DEGs) in each dose group using a loose criterion of fold change (FC) >1.5 and unadjusted p < 0.05, regardless of whether the analysis was conducted within each gender group or with both gender groups combined. No dose-dependent effect was observed on the number of DEGs. In addition, none of these genes had a false discovery rate (FDR) <0.05 after correction for multiple testing. These results in combination with the observation that thymus-to-body-weight ratios were not affected and no histopathological abnormalities were identified indicate that in utero exposure to silver ions up to 26.0 mg/kg (equivalent to 40.0 mg/kg silver acetate) did not have an adverse effect on the developing thymus.
PloS one, 2014
The Tox21 program calls for transforming toxicology testing from traditional in vivo tests to les... more The Tox21 program calls for transforming toxicology testing from traditional in vivo tests to less expensive and higher throughput in vitro methods. In developmental toxicology, a spectrum of alternative methods including cell line based tests has been developed. In particular, embryonic stem cells (ESCs) have received widespread attention as a promising alternative model for developmental toxicity assessment. Here, we characterized gene expression changes during mouse ESC differentiation and their modulation by developmental toxicants. C57BL/6 ESCs were allowed to differentiate spontaneously and RNA of vehicle controls was collected at 0, 24, 48, 72, 96, 120 and 168 h after embryoid body (EB) formation; RNA of compound-exposed EBs were collected at 24 h. Samples were hybridized to Affymetrix Mouse Gene 2.0 ST Array; using stringent cut-off criteria of Bonferroni-adjusted p<0.05 and fold change >2.0, a total of 1996 genes were found differentially expressed among the vehicle c...
Wei sheng wu xue bao = Acta microbiologica Sinica, 1998
A lipase-producing bacterium strain was isolated from soil and was identified as Pseudomonas sp..... more A lipase-producing bacterium strain was isolated from soil and was identified as Pseudomonas sp.. Its lipase yield was improved 2.25-fold by combined treatment of UV irradiation and NTG. The lipase fermentation condition for the mutant strain was optimized with Plackett-Burman design and Response Surface Analysis (RSA), and the formula of the optimum medium suitable for industrial scale fermentation was thereby established. A maximum yield of 87.5 U/ml was obtained.
Sheng wu hua xue yu sheng wu wu li xue bao Acta biochimica et biophysica Sinica, 1997
The asymmetric esterification of octanoic acid with racemic 2-octanol catalyzed by a lipase from ... more The asymmetric esterification of octanoic acid with racemic 2-octanol catalyzed by a lipase from Pseudomonas sp. was investigated in several typical solvents. It was found that the catalytic activity and the enantioselectivity of the enzyme were governed by different physicochemical parameters of the solvent employed. While the former depended on the hydrophobicity (lgP) of the solvent, by contrast the latter was a function of the dielectric constant and the dipole moment. A mechanistic model for the binding site of the enzyme was postulated to rationalize this phenomenon based on the results of the kinetic studies of the reaction in some representative solvents.
The Biochemical journal, Jan 15, 1998
The reactivation of the homodimeric triosephosphate isomerases (TIMs) from Trypanosoma brucei, T.... more The reactivation of the homodimeric triosephosphate isomerases (TIMs) from Trypanosoma brucei, T. cruzi, Leishmania mexicana and humans was determined after their denaturation with guanidine hydrochloride. In the range of 2-32 microg of T. brucei TIM per ml and 0.2-5 microg of the other enzymes per ml, the rate and extent of TIM reactivation depended on protein concentration, indicating that at these protein concentrations, the rate-limiting step of reactivation is monomer association and not monomer folding. The rate of monomer association was more than one order of magnitude lower in the T. brucei enzyme than in the other three enzymes. Suramin is a drug of choice in the treatment of sleeping sickness, but its mechanism of action is not known. At micromolar concentrations, Suramin inhibited the reactivation of the four enzymes, but the extent of inhibition by Suramin decreased with increasing protein concentration as consequence of a diminution of the life time of the folded monom...
Biomarkers in medicine, 2010
Biomarkers play a pivotal role in the early detection and diagnosis of cancer. Accurate quantitat... more Biomarkers play a pivotal role in the early detection and diagnosis of cancer. Accurate quantitation of certain biomarkers is crucial to reach correct treatment decisions. In practice, immunohistochemistry (IHC) remains the most important diagnostic technique to evaluate protein biomarker expression in tissue biopsies. However, IHC has largely been qualitative. Low specificity of the mammalian IgG antibodies used to capture the analytes and instability of fluorescence from the organic dyes used as the detecting agents are among the major factors that have impeded the development of quantitative IHC. Avian IgY antibodies have many attractive biochemical, immunological and production advantages over IgGs and are, therefore, better substitutes in diagnostic applications. Using IgY in immunoassays can potentially eliminate false positives and often results in low background and interference. Quantum dots (QDs) have recently emerged as a novel class of fluorophores, promising for many bi...
Recent Advances in Nanotechnology, 2011
International journal of toxicology, Jul 6, 2014
Mustard gas (sulfur mustard [SM], bis-[2-chloroethyl] sulfide) is a vesicating chemical warfare a... more Mustard gas (sulfur mustard [SM], bis-[2-chloroethyl] sulfide) is a vesicating chemical warfare agent and a potential chemical terrorism agent. Exposure of SM causes debilitating skin blisters (vesication) and injury to the eyes and the respiratory tract; of these, the respiratory injury, if severe, may even be fatal. Therefore, developing an effective therapeutic strategy to protect against SM-induced respiratory injury is an urgent priority of not only the US military but also the civilian antiterrorism agencies, for example, the Homeland Security. Toward developing a respiratory medical countermeasure for SM, four different classes of therapeutic compounds have been evaluated in the past: anti-inflammatory compounds, antioxidants, protease inhibitors and antiapoptotic compounds. This review examines all of these different options; however, it suggests that preventing cell death by inhibiting apoptosis seems to be a compelling strategy but possibly dependent on adjunct therapies u...