FBXO32-mediated degradation of PTEN promotes lung adenocarcinoma progression.

FBXO32, a member of the F-box protein family, is known to play both oncogenic and tumor-suppressive roles in different cancers. However, the functions and the molecular mechanisms regulated by FBXO32 in lung adenocarcinoma (LUAD) remain unclear. Here, we report that FBXO32 is overexpressed in LUAD compared with normal lung tissues, and high expression of FBXO32 correlates with poor prognosis in LUAD patients. Firstly, we observed with a series of functional experiments that FBXO32 alters the cell cycle and promotes the invasion and metastasis of LUAD cells. We further corroborate our findings using in vivo mouse models of metastasis and confirmed that FBXO32 positively regulates LUAD tumor metastasis. Using a proteomic-based approach combined with computational analyses, we found a positive correlation between FBXO32 and the PI3K/AKT/mTOR pathway, and identified PTEN as a FBXO32 interactor. More important, FBXO32 binds PTEN via its C-terminal substrate binding domain and we also validated PTEN as a bona fide FBXO32 substrate. Finally, we demonstrated that FBXO32 promotes EMT and regulates the cell cycle by targeting PTEN for proteasomal-dependent degradation. In summary, our study highlights the role of FBXO32 in promoting the PI3K/AKT/mTOR pathway via PTEN degradation, thereby fostering lung adenocarcinoma progression.

Water Intake and Adiposity Outcomes among Overweight and Obese Individuals: A Systematic Review and Meta-Analysis of Randomized Controlled Trials.

BACKGROUND: Water consumption is believed to be a key factor in weight management strategies, yet the existing literature on the subject yields inconsistent findings. To systematically assess the scientific evidence regarding the effect of water intake on adiposity, we conducted a systematic review and meta-analysis of randomized controlled trials (RCTs) among overweight and obese populations. METHODS: PubMed and Embase were searched for relevant articles published up to December 2023. The summary weighted mean difference (WMD) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. RESULTS: In this meta-analysis of eight RCTs, interventions to promote water intake or to substitute water for other beverages as compared to the control group resulted in a summary WMD of -0.33 kg (95% CI = -1.75-1.08, I2 = 78%) for body weight, -0.23 kg/m2 (95% CI = -0.55-0.09, I2 = 0%) for body mass index (BMI), and 0.05 cm (95% CI = -1.20-1.30, I2 = 40%) for waist circumference (WC). Among RCTs substituting water for artificially sweetened beverages, summary WMD was 1.82 kg (95% CI = 0.97-2.67, I2 = 0%) for body weight and 1.23 cm (95% CI = -0.03-2.48, I2 = 0%) for WC. Conversely, among RCTs substituting water for sugar-sweetened beverages, summary WMD was -0.81 kg (95% CI = -1.66-0.03, I2 = 2%) for body weight and -0.96 cm (95% CI = -2.06-0.13, I2 = 0%) for WC. CONCLUSIONS: In conclusion, water intake may not significantly impact adiposity among overweight and obese individuals. However, replacing sugar-sweetened beverages with water might offer a modest benefit in inducing weight loss.

Water intake and obesity: By amount, timing, and perceived temperature of drinking water.

Water intake has been suggested to be associated with weight control, but evidence for optimal water intake in terms of amount, timing, and temperature is sparse. Additionally, genetic predisposition to obesity, which affects satiety and energy expenditure, might interact with water intake in regulating individual adiposity risk. We conducted a cross-sectional study recruiting 172 Korean adults. Information on water intake and lifestyle factors was collected through self-reported questionnaires, and height, weight, and waist circumference (WC) were measured by researchers. The oral buccal swab was performed for genotyping of FTO rs9939609, MC4R rs17782313, BDNF rs6265 and genetic risk of obesity was calculated. Linear regression was performed to estimate mean difference in body mass index (BMI) and WC by water intake and its 95% confidence interval (95% CI). As a sensitivity analysis, logistic regression was performed to estimate odds ratio (OR) of obesity/overweight (BMI of ≥23kg/m2; WC of ≥90cm for men and of ≥80cm for women) and its 95% CI. Drinking >1L/day was significantly associated with higher BMI (mean difference: 0.90, 95% CI 0.09, 1.72) and WC (mean difference: 3.01, 95% CI 0.62, 5.41) compared with drinking ≤1L/day. Independent of total water intake, drinking before bedtime was significantly associated with lower BMI (mean difference: -0.98, 95% CI -1.91, -0.05). The results remained consistent when continuous BMI and WC were analyzed as categorical outcomes. By perceived temperature, drinking >1L/day of cold water was associated with higher BMI and WC compared with drinking ≤1L/day of water at room-temperature. By genetic predisposition to obesity, a positive association between water intake and WC was confined to participants with low genetic risk of obesity (P interaction = 0.04). In conclusion, amount, timing, and perceived temperature of water intake may be associated with adiposity risk and the associations might vary according to genetic predisposition to obesity.

Crosstalk between extracellular vesicles and tumor-associated macrophage in the tumor microenvironment.

In concert with hijacking key genes to drive tumor progression, cancer cells also have the unique ability to dynamically interact with host microenvironment and discreetly manipulate the surrounding stroma, also known as the tumor microenvironment (TME), to provide optimal conditions for tumor cells to thrive and evade host immunity. Complex cellular crosstalk and molecular signaling between cancer cells, surrounding non-malignant cells, and non-cellular components are involved in this process. While intercellular communication traditionally centers around chemokines, cytokines, inflammatory mediators, and growth factors, emerging pathways involving extracellular vesicles (EVs) are gaining increasing attention. The immunosuppressive TME is created and maintained in part by the large abundance of tumor-associated macrophages (TMAs), which are associated with drug resistance, poor prognosis, and have emerged as potential targets for cancer immunotherapy. TMAs are highly dynamic, and can be polarized into either M1 or M2-like macrophages. EVs are efficient cell-cell communication molecules that have been catapulted to the center of TMA polarization. In this article, we provide detailed examination of the determinative role of EVs in sustaining the TME through mediating crosstalk between tumor cells and tumor-associated macrophages.

FAM3A Ameliorates Brain Impairment Induced by Hypoxia-Ischemia in Neonatal Rat.

Hypoxia-ischemia (HI) during crucial periods of brain formation can lead to changes in brain morphology, propagation of neuronal stimuli, and permanent neurodevelopmental impairment, which can have profound effects on cognitive function later in life. FAM3A, a subgroup of family with sequence similarity 3 (FAM3) gene family, is ubiquitously expressed in almost all cells. Overexpression of FAM3A has been evidenced to reduce hyperglycemia via the PI3K/Akt signaling pathway and protect mitochondrial function in neuronal HT22 cells. This study aims to evaluate the protective role of FAM3A in HI-induced brain impairment. Experimentally, maternal rats underwent uterine artery bilateral ligation to induce neonatal HI on day 14 of gestation. At 6 weeks of age, cognitive development assessments including NSS, wire grip, and water maze were carried out. The animals were then sacrificed to assess cerebral mitochondrial function as well as levels of FAM3A, TNF-α and IFN-γ. Results suggest that HI significantly reduced FAM3A expression in rat brain tissues, and that overexpression of FAM3A through lentiviral transduction effectively improved cognitive and motor functions in HI rats as reflected by improved NSS evaluation, cerebral water content, limb strength, as well as spatial learning and memory. At the molecular level, overexpression of FAM3A was able to promote ATP production, balance mitochondrial membrane potential, and reduce levels of pro-inflammatory cytokines TNF-α and IFN-γ. We conclude that FAM3A overexpression may have a protective effect on neuron morphology, cerebral mitochondrial as well as cognitive function. Created with Biorender.com.

Association of cerebral spinal fluid copper imbalance in amyotrophic lateral sclerosis.

A plethora of environmental risk factors has been persistently implicated in the pathogenesis of amyotrophic lateral sclerosis (ALS), including metal/metalloids. This study aimed to examine potential associations between cerebral spinal fluid (CSF) metal/metalloids and ALS risks. CSF concentrations of copper (Cu), nickel (Ni), mercury (Hg), arsenic (As), manganese (Mn), and iron (Fe) in ALS (spinal- and bulbar-onset) patients and controls were measured using inductively coupled plasma mass spectrometry (ICP-MS). Results from this study revealed marked differences between control, spinal-onset, and bulbar-onset groups. We report that Cu levels were lower in the ALS and spinal-onset groups compared to the control group. Ni level were higher in the spinal-onset group compared to the control and bulbar-onset groups. In addition, associations between CSF metal/metalloid levels with disease severity, sex, and serum triglycerides were also examined to broach the potential relevance of neurotoxic metal/metalloids in ALS disease heterogeneity.

Quantifying the parallel mediation influence of body mass index and depression on physical activity and cognitive function among 3,611 Chinese older adults.

Background: Engagement in physically active lifestyles brings multidimensional health benefits including better cognitive function. While prior studies examined the link between physical activity and cognitive function, a remaining unanswered question is what modifiable factors channel such effects. Objective: This study investigates the extent to which subject's body mass index (BMI) and depression mediate the link between physical activity and cognitive function among older adults in China. Methods: This study builds a parallel structural equation model utilizing the 2013-2018 China Health and Retirement Longitudinal Study (CHARLS) dataset. We screened a total of 14,724 subjects, among which 3,611 subjects met the inclusion criteria. Physical activity, depression, and cognitive function are measured using the International Physical Activity Questionnaire (IPAQ), Center for Epidemiological Research Depression Scale (CES-D), and Mini-Mental State Examination (MMSE) instruments. Results: Parallel mediation analyses indicate that depression significantly mediates the link between physical activity and cognitive function (std. ß = 0.023, p-value = 0.010), while no significant mediation was observed via BMI (std. ß = 0.005, p-value = 0.155). Findings also show that physical activity is positively associated with cognitive function (std. ß = 0.104, p-value = 0.004), whereas physical activity is inversely associated with BMI (std. ß = -0.072, p-value = 0.045). Both BMI (std. ß = -0.071, p-value = 0.042) and depression (std. ß = -0.199, p-value = 0.001) are negatively associated with cognitive function. Conclusion: This study quantifies the positive association between physical activity and cognitive function in older Chinese adults, and uncovers a significant mediation channel occurring through depression. From a clinical perspective, physical behavioral modifications can lead to linked improvements in both mental and cognitive wellbeing for older adults.

Post-Diagnosis Vitamin D Supplement Use and Survival among Cancer Patients: A Meta-Analysis.

Vitamin D administered pre-diagnostically has been shown to reduce mortality. Emerging evidence suggests a role of post-diagnosis vitamin D supplement intake for survival among cancer patients. Thus, we conducted a meta-analysis to evaluate the relationship. PubMed and Embase were searched for relevant observational cohort studies and randomized trials published through April 2022. Summary relative risk (SRR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The SRR for post-diagnosis vitamin D supplement use vs. non-use, pooling cohort studies and randomized trials, was 0.87 (95% CI, 0.78-0.98; p = 0.02; I2 = 0%) for overall survival, 0.81 (95% CI, 0.62-1.06; p = 0.12; I2 = 51%) for progression-free survival, 0.86 (95% CI, 0.72-1.03; p = 0.10; I2 = 0%) for cancer-specific survival, and 0.86 (95% CI, 0.64-1.14; p = 0.29; I2 = 0%) for relapse. Albeit not significantly heterogeneous by variables tested, a significant inverse association was limited to cohort studies and supplement use during cancer treatment for overall survival, and to studies with ≤3 years of follow-up for progression-free survival. Post-diagnosis vitamin D supplement use was associated with improved overall survival, but not progression-free or cancer-specific survival or relapse. Our findings require confirmation, as randomized trial evidence was insufficient to establish cause-and-effect relationships.

Acute nitrous oxide-induced neuropathy mimicking Guillain-Barré syndrome.

The early clinical features of nitrous oxide (N2 O)-induced neuropathy were mimicking that of Guillain-Barré syndrome (GBS). We aimed to explore clinical and laboratory characteristics of N2 O-induced neuropathy in comparison with GBS. We retrospectively reviewed data of 15 patients with N2 O-induced neuropathy and compared them with 15 GBS patients. The age of the N2 O-induced neuropathy group was significantly younger than that in the GBS group (22 ± 5 vs 45 ± 17). Paresthesia was more common in N2 O-induced neuropathy group (100% vs 53.3%). The proportion of distal upper limbs weakness was lower than that in GBS group (20.0% vs 93.3%). There was no significant difference in the distal weakness of the lower limbs (100% vs 80.0%). The incidence of motor conduction block and compound muscle action potential amplitude reduction in upper limbs was lower than that in GBS group (6.7% vs 60.0%; 26.7% vs 80.0%). The sensory nerve action potential amplitude drop in the lower limbs was more severe than that in GBS group (53.3% vs 0). The increase of Mean corpuscular volume (MCV) was more pronounced compared to GBS group (96.97 ± 6.00 vs 88.55 ± 5.41). High homocysteine levels were more common in N2 O-related group [29.80(11.60, 70.50) vs 14.35(9.22, 19.30)]. Typical clinical features of the acute N2 O neuropathy appears to be a myeloneuropathy, affecting the lower limbs more than the upper limbs, mixed axonal-demyelinating electrophysiological performance, higher homocysteine level, and larger MCV and common posterior spinal cord involvement in cervical segment.

Milk Intake in Early Life and Later Cancer Risk: A Meta-Analysis.

Dairy consumption in adulthood has been demonstrated to influence cancer risk. Although childhood and adolescence represent critical periods of rapid growth, the relationship between milk intake in early life and later cancer risk is unclear. Thus, we examined this relationship by conducting a meta-analysis of the observational studies. PubMed and Embase were searched for relevant articles that were published throughout December 2021. The summary relative risk (RR) and 95% confidence interval (CI) were estimated using the DerSimonian-Laird random-effects model. The summary RR for the highest vs. lowest milk intake was 0.83 (95% CI = 0.69-1.00; p = 0.05; I2 = 60%; seven studies) for breast cancer, 0.98 (95% CI = 0.72-1.32; p = 0.88; I2 = 51%; four studies) for prostate cancer, and 0.90 (95% CI = 0.42-1.93; p = 0.78; I2 = 83%; three studies) for colorectal cancer. No evidence of an association emerged in subgroup analyses of menopausal status, cancer stage, fat content of milk, life stage of milk intake, or study design. Consistent results were observed in the meta-analyses using total dairy intake. In conclusion, milk intake during childhood and adolescence might not be associated with risks of breast, prostate, and colorectal cancer later in life. Given the small number of studies that were included in our meta-analysis, and the high heterogeneity, more studies are warranted for a definitive conclusion.

Comparative assessment of blood Metal/metalloid levels, clinical heterogeneity, and disease severity in amyotrophic lateral sclerosis patients.

Amyotrophic lateral sclerosis is an unremitting neurodegenerative (ND) disease characterized by progressive and fatal loss of motor neuron function. While underlying mechanisms for ALS susceptibility are complex, current understanding suggests that interactions between age, genetic, and environmental factors may be the key. Environmental exposure to metal/metalloids has been implicated in various ND diseases including ALS, Alzheimer's Disease (AD), and Parkinson's Disease (PD). However, most of currently available population-based ALS studies in relation to metal exposure are based on individuals from European ancestry, while East Asian populations, especially cohorts from China, are less well-characterized. This study aims to examine the association between metal/metalloid levels and ALS onset by evaluating blood cadmium (Cd), lead (Pb), Cu, Zn, calcium (Ca), magnesium (Mg), and iron (Fe) levels in controls and sporadic ALS patients from North Western China. We report that Cu and Fe levels are found at higher levels in ALS patients compared to the controls. Spinal and bulbar onset patients show significant difference in Ca levels. Moreover, Cd, Pb, Cu, and Ca levels are positively correlated with high disease severity. Results from this study may provide new insights for understanding not only the role of metal/metalloids in ALS susceptibility, but also progression and forms of onset.

Exosomal Proteins and miRNAs as Mediators of Amyotrophic Lateral Sclerosis.

Recent advances in the neurobiology and neurogenerative diseases have attracted growing interest in exosomes and their ability to carry and propagate active biomolecules as a means to reprogram recipient cells. Alterations in exosomal protein content and nucleic acid profiles found in human biological fluids have been correlated with various diseases including amyotrophic lateral sclerosis (ALS). In ALS pathogenesis, these lipid-bound nanoscale vesicles have emerged as valuable candidates for diagnostic biomarkers. Moreover, their capacity to spread misfolded proteins and functional non-coding RNAs to interconnected neuronal cells make them putative mediators for the progressive motor degeneration found remarkably apparent in ALS. This review outlines current knowledge concerning the biogenesis, heterogeneity, and function of exosomes in the brain as well as a comprehensive probe of currently available literature on ALS-related exosomal proteins and microRNAs. Lastly, with the rapid development of employing nanoparticles for drug delivery, we explore the therapeutic potentials of exosomes as well as underlying limitations in current isolation and detection methodologies.

RUNX2/miR­31/SATB2 pathway in nickel­induced BEAS­2B cell transformation.

Nickel (Ni) compounds are classified as Group 1 carcinogens by the International Agency for Research on Cancer (IARC) and are known to be carcinogenic to the lungs. In our previous study, special AT­rich sequence­binding protein 2 (SATB2) was required for Ni­induced BEAS­2B cell transformation. In the present study, a pathway that regulates the expression of SATB2 protein was investigated in Ni­transformed BEAS­2B cells using western blotting and RT­qPCR for expression, and soft agar, migration and invasion assays for cell transformation. Runt­related transcription factor 2 (RUNX2), a master regulator of osteogenesis and an oncogene, was identified as an upstream regulator for SATB2. Ni induced RUNX2 expression and initiated BEAS­2B transformation and metastatic potential. Previously, miRNA­31 was identified as a negative regulator of SATB2 during arsenic­induced cell transformation, and in the present study it was identified as a downstream target of RUNX2 during carcinogenesis. miR­31 expression was reduced in Ni­transformed BEAS­2B cells, which was required to maintain cancer hallmarks. The expression level of miR­31 was suppressed by RUNX2 in BEAS­2B cells, and this increased the expression level of SATB2, initiating cell transformation. Ni caused the repression of miR­31 by placing repressive marks at its promoter, which in turn increased the expression level of SATB2, leading to cell transformation.

Arsenic: A Global Environmental Challenge.

Arsenic is a naturally occurring metalloid and one of the few metals that can be metabolized inside the human body. The pervasive presence of arsenic in nature and anthropogenic sources from agricultural and medical use have perpetuated human exposure to this toxic and carcinogenic element. Highly exposed individuals are susceptible to various illnesses, including skin disorders; cognitive impairment; and cancers of the lung, liver, and kidneys. In fact, across the globe, approximately 200 million people are exposed to potentially toxic levels of arsenic, which has prompted substantial research and mitigation efforts to combat this extensive public health issue. This review provides an up-to-date look at arsenic-related challenges facing the global community, including current sources of arsenic, global disease burden, arsenic resistance, and shortcomings of ongoing mitigation measures, and discusses potential next steps.

Dynamic Activity of Histone H3-Specific Chaperone Complexes in Oncogenesis.

Canonical histone H3.1 and variant H3.3 deposit at different sites of the chromatin via distinct histone chaperones. Histone H3.1 relies on chaperone CAF-1 to mediate replication-dependent nucleosome assembly during S-phase, while H3.3 variant is regulated and incorporated into the chromatin in a replication-independent manner through HIRA and DAXX/ATRX. Current literature suggests that dysregulated expression of histone chaperones may be implicated in tumor progression. Notably, ectopic expression of CAF-1 can promote a switch between canonical H3.1 and H3 variants in the chromatin, impair the chromatic state, lead to chromosome instability, and impact gene transcription, potentially contributing to carcinogenesis. This review focuses on the chaperone proteins of H3.1 and H3.3, including structure, regulation, as well as their oncogenic and tumor suppressive functions in tumorigenesis.

Polyadenylation of Histone H3.1 mRNA Promotes Cell Transformation by Displacing H3.3 from Gene Regulatory Elements.

Replication-dependent canonical histone messenger RNAs (mRNAs) do not terminate with a poly(A) tail at the 3' end. We previously demonstrated that exposure to arsenic, an environmental carcinogen, induces polyadenylation of canonical histone H3.1 mRNA, causing transformation of human cells in vitro. Here we report that polyadenylation of H3.1 mRNA increases H3.1 protein, resulting in displacement of histone variant H3.3 at active promoters, enhancers, and insulator regions, leading to transcriptional deregulation, G2/M cell-cycle arrest, chromosome aneuploidy, and aberrations. In support of these observations, knocking down the expression of H3.3 induced cell transformation, whereas ectopic expression of H3.3 attenuated arsenic-induced cell transformation. Notably, arsenic exposure also resulted in displacement of H3.3 from active promoters, enhancers, and insulator regions. These data suggest that H3.3 displacement might be central to carcinogenesis caused by polyadenylation of H3.1 mRNA upon arsenic exposure. Our findings illustrate the importance of proper histone stoichiometry in maintaining genome integrity.

PBMC gene expression profiles of female Bangladeshi adults chronically exposed to arsenic-contaminated drinking water.

Arsenic, a class I human carcinogen, is ubiquitously found throughout the environment and around the globe, posing a great public health concern. Notably, Bangladesh and regions of West Bengal have been found to have high levels (0.5-4600 µg/L) of arsenic drinking water contamination, and approximately 50 million of the world's 200 million people chronically exposed to arsenic in Bangladesh alone. This study was carried out to examine genome-wide gene expression changes in individuals chronically exposed to arsenic-contaminated drinking water. Our study population includes twenty-nine Bangladeshi female participants with urinary arsenic levels ranging from 22.32 to 1828.12 µg/g creatinine. RNA extracted from peripheral blood mononuclear cells (PBMCs) were evaluated using RNA-Sequencing analysis. Our results indicate that a total of 1,054 genes were significantly associated with increasing urinary arsenic levels (FDR p < 0.05), which include 418 down-regulated and 636 up-regulated genes. Further Ingenuity Pathway Analysis revealed potential target genes (DAPK1, EGR2, APP), microRNAs (miR-155, -338, -210) and pathways (NOTCH signaling pathway) related to arsenic carcinogenesis. The selection of female-only participants provides a homogenous study population since arsenic has significant sex dependent effects, and the wide exposure range provides new insight for key gene expression changes that correlate with increasing urinary arsenic levels.

Molecular and epigenetic mechanisms of Cr(VI)-induced carcinogenesis.

Chromium (Cr) is a naturally occurring metallic element found in the Earth's crust. While trivalent chromium ([Cr(III)] is considered non-carcinogenic, hexavalent chromium [Cr(VI)] has long been established as an IARC class I human carcinogen, known to induce cancers of the lung. Current literature suggests that Cr(VI) is capable of inducing carcinogenesis through both genetic and epigenetic mechanisms. Although much has been learned about the molecular etiology of Cr(VI)-induced lung carcinogenesis, more remains to be explored. In particular, the explicit epigenetic alterations induced by Cr(VI) in lung cancer including histone modifications and miRNAs, remain understudied. Through comprehensive review of available literature found between 1973 and 2019, this article provides a summary of updated understanding of the molecular mechanisms of Cr(VI)-carcinogenesis. In addition, this review identifies potential research gaps in the areas of histone modifications and miRNAs, which may prompt new niches for future research.

Deregulation of SATB2 in carcinogenesis with emphasis on miRNA-mediated control.

The special AT-rich DNA binding protein (SATB2) is a nuclear matrix-associated protein and an important transcription factor for biological development, gene regulation and chromatin remodeling. Aberrant regulation of SATB2 has been found to highly correlate with various types of cancers including lung, colon, prostate, breast, gastric and liver. Recent studies have revealed that a subset of small non-coding RNAs, termed microRNAs (miRNAs), are important regulators of SATB2 function. As post-transcriptional regulators, miRNAs have been found to have fundament importance maintaining normal cellular development. Evidence suggests that multiple miRNAs, including miR-31, miR-34, miR-182, miR-211, miR-599, are capable of regulating SATB2 in cancers of the lung, liver, colon and breast. This review examines the molecular functions of SATB2 and miRNAs in the text of cancer development and potential strategies for cancer therapy with a focus on systemic miRNA delivery.

Role of transient receptor potential cation channel subfamily V member 1 (TRPV1) on ozone-exacerbated allergic asthma in mice.

Around the globe, worsening air pollution is spawning major public health and environmental concerns, especially in the poorest and most populous cities. As a major secondary air pollutant, ozone is a potential risk factor for exacerbated asthma, although the underlying mechanisms remain uncertain. In this study, we aim to investigate the role of ozone on asthma exacerbation using a classic asthmatic model with allergic airway inflammation by treating Balb/c mice with ovalbumin (OVA). Our study shows ozone exposure significantly exacerbated OVA-induced asthmatic phenotypes, including serum immunoglobulin, Th cytokines, inflammatory cell counts, mucus production, airway remodeling, and airway hyper-responsiveness (AHR). Interestingly, expression of transient receptor potential cation channel subfamily V member1 (TRPV1) was also significantly elevated in ozone-exacerbated asthmatic mice and that treatment with TRPV1 antagonist effectively suppressed AHR, airway inflammation and remodeling. The underlying mechanisms of these effects may be associated with suppression of neuropeptide calcitonin gene-related peptide (CGRP) and thymic stromal lymphopoietin (TSLP), an epithelial cell-derived cytokine. Base on the role of TRPV1 in allergic asthma, this study further revealed that inhibition of TRPV1 by TRPV1 antagonist has significant anti-inflammatory effects on ozone-induced asthma exacerbation in this study. Induction of TRPV1 expression may be an important mechanism underlying the increased risks for asthma after exposure to environmental pollutants.