This study was undertaken to determine whether there was an association between coarse particles (PM_2.5–10) levels and frequency of hospital admissions for respiratory diseases (RD) in Kaohsiung, Taiwan. Hospital admissions for RD including chronic obstructive pulmonary disease (COPD), asthma, and pneumonia, and ambient air pollution data levels for Kaohsiung were obtained for the period from 2006 to 2010. The relative risk of hospital admissions for RD was estimated using a case-crossover approach, controlling for weather variables, day of the week, seasonality, and long-term time trends. For the single pollutant model (without adjustment for other pollutants), increased rate of admissions for RD were significantly associated with higher coarse PM levels only on cool days (<25 °C), with a 10 µg/m³ elevation in PM_2.5–10 concentrations associated with a 3% (95% CI = 1%–5%) rise in COPD admissions, 4% (95% CI = 1%–7%) increase in asthma admissions, and 3% (95% CI = 2%–4%) rise in pneumonia admissions. No significant associations were found between coarse particle levels and the number of hospital admissions for RD on warm days. In the two-pollutant models, PM_2.5–10 levels remained significantly correlated with higher rate of RD admissions even controlling for sulfur dioxide, nitrogen dioxide, carbon monoxide, or ozone on cool days. This study provides evidence that higher levels of PM_2.5–10 enhance the risk of hospital admissions for RD on cool days.

Background: Paclitaxel is wildly used in chemotherapy, however, the adverse drug reactions (ADRs) occurred frequently. Various novel nano-based paclitaxel delivery systems were developed. The aim performed systemically review and meta-analyses to evaluate the effect adverse drug reactions (ADRs) of paclitaxel and its nano-based delivery systems. Methods: Systematically searched PubMed, Embase, Web of Science, Cochrane, Clinicalkey, Clinicaltrial.com, ASCO and ESMO. Data of adverse effect were analyzed to odds ratio (ORs) with 95% confidence interval (CI). The quality of studies was assessed with CASP Randomised Controlled Trial Checklist. Statistical analysis was used WinBUGS software (version 1.4.3) with the NetMetaXL interface (version 1.6.1). Results: Twenty-one studies, including 7011 patients and 6 paclitaxel formulations fulfilled the inclusion criteria. In all grade hypersensitivity reactions, comparing to SB-P, people with Lip-P had 0.19 times (95% CI= 0.02, 1.3) of chance, with Nab-P had 0.47 times (95% CI= 0.11, 1.40) of chance, with PPX had 0.44 times (95% CI= 0.03, 5.7) of chance for all grade adverse effect. In All grad neutropenia, comparing to Lip-P, people with SB-P had 0.83 times (95% CI= 0.15, 4.81) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.73 times (95% CI= 0.22, 2.42) of chance for all grade adverse effect. In leucopenia, comparing to Nab-P, people with SB-P had 0.66 times (95% CI= 0.50, 0.87) of chance for all grade adverse effect; comparing to PM-P, people with SB-P had 0.64 times (95% CI= 0.32, 1.16) of chance for all grade adverse effect. The rate of incidence in peripheral sensory neuropathy, myalgias and arthralgias tend to no significant differences between different formulations. Conclusion: Nano-based paclitaxel delivery resulted in fewer hypersensitivity reactions than solvent-based delivery. However, the incidence of neutropenia and leucopenia was higher in nano-based than solvent-based paclitaxel delivery. Dose-dependent ADRs were more frequent in paclitaxel anticancer treatment.

Lung cancer is the leading cause of cancer deaths in the world, with a five-year survival rate of less than 30%. Clinically effective chemotherapeutic treatments at the initial stage may eventually face the dilemma of no drug being effective due to drug resistance; therefore, finding new effective drugs for lung cancer treatment is a necessary and important issue. Compounds capable of further increasing the oxidative stress of cancer cells are considered to have anticancer potential because they possessed the ability to induce apoptosis. This study mainly investigated the effects of BA6 (heteronemin), the marine sponge sesterterpene, on lung cancer cell apoptosis, via modulation of mitochondrial reactive oxygen species (mtROS) and oxidative phosphorylation (OXPHOS). BA6 has cellular cytotoxic activities against a variety of cancer cell lines, but it has no effect on nontumor cells. The BA6-treated lung cancer cells show a significant increase in both cellular ROS and mtROS, which in turn caused the loss of mitochondrial membrane potential (MMP). The increase of oxidative stress in lung cancer cells treated with BA6 was accompanied by a decrease in the expression of antioxidant enzymes Cu/Zn SOD, MnSOD, and catalase. In addition, OXPHOS performed in the mitochondria and glycolysis in the cytoplasm were inhibited, which subsequently reduced downstream ATP production. Pretreatment with mitochondria-targeted antioxidant MitoTEMPO reduced BA6-induced apoptosis through the mitochondria-dependent apoptotic pathway, which was accompanied by increased cell viability, decreased mtROS, enhanced MMP, and suppressed expression of cleaved caspase-3 and caspase-9 proteins. In conclusion, the results of this study clarify the mechanism of BA6-induced apoptosis in lung cancer cells via the mitochondrial apoptotic pathway, suggesting that it is a potentially innovative alternative to the treatment of human lung cancer.

Weekly rifapentine and isoniazid therapy (known as 3HP) for latent tuberculosis infection (LTBI) is increasingly used, but systemic drug reactions (SDR) remain a major concern. Methods: We prospectively recruited two LTBI cohorts who received the 3HP regimen. In the single-nucleotide polymorphism (SNP) cohort, we collected clinical information of SDRs and examined the NAT2, CYP2E1, and AADAC SNPs. In the pharmacokinetic (PK) cohort, we measured plasma drug and metabolite levels at 6 and 24 h after 3HP administration. The generalised estimating equation model was used to identify the factors associated with SDRs. Candidate SNPs predicting SDRs were validated in the PK cohort. A total of 177 participants were recruited into the SNP cohort and 129 into the PK cohort, with 14 (8%) and 13 (10%) in these two cohorts developing SDRs, respectively. In the SNP cohort, NAT2 rs1041983 (TT vs. CC+CT, odds ratio [OR] [95% CI]: 7.00 [2.03–24.1]) and CYP2E1 rs2070673 (AA vs. TT+TA, OR [95% CI]: 3.50 [1.02–12.0]) were associated with SDR development. In the PK cohort, isoniazid level 24 h after 3HP administration (OR [95% CI]: 1.61 [1.15–2.25]) was associated with SDRs. Additionally, the association between the NAT2 SNP and SDRs was validated in the PK cohort (rs1041983 TT vs. CC+CT, OR [95% CI]: 4.43 [1.30–15.1]). Conclusions: Isoniazid played a role in the development of 3HP-related SDRs. This could provide insight for further design of a more optimal regimen for latent TB infection.

Triple-negative breast cancer (TNBC) is an aggressive type of breast cancer with a worse prognosis than other types. There are currently no specific approved treatments for TNBC. Albumin is a promising biomimetic material that may be fabricated into nanoparticles to possibly exert passive effects on targeted tumors. Irinotecan has been extensively used in clinical settings, although a high dosage is required due to its low efficiency of conversion into the active metabolite SN-38, also known as 7-ethyl-10-hydroxy-camptothecin. The aim of this work was to optimize SN-38-loaded bovine serum albumin nanoparticles (sBSANPs) and evaluate their potency against TNBC. The sBSANPs were characterized by a small size of about 134–264 nm, a negative charge of −37 to −40 mV, an entrapment efficiency of 59–71%, and a particle yield of 65–86%. The cytotoxicity assays using sBSANPs showed a higher potency specifically against both MDA-MB-468 and MDA-MB-231 cells (ER−, PR−, HER2−) compared to MCF-7 (ER+, PR+, HER2−), and exhibited an extremely low IC₅₀ at the nanomolar levels (2.01–6.82 nM). The release profiles indicated that SN-38 presented an initial burst release within 12 h, and sBSANPs had a slow release pattern. Flow cytometry results showed that the fluorescence intensity of sBSANPs was significantly higher than that of the control group. The confocal images also confirmed that sBSANPs were taken up by MDA-MB-468 cells. Moreover, we found that a larger BSANP size resulted in an increased hemolytic effect. In vivo animal studies demonstrated that loading of SN-38 into bovine serum albumin nanoparticles could minimize the initial concentration without extending the elimination half-life, but significantly minimized the Cmax (p < 0.001) as compared with irinotecan treatment.

Background: Adult asthma is phenotypically heterogeneous with unclear aetiology. We aimed to evaluate the potential contribution of environmental exposure and its ensuing response to asthma and its heterogeneity.Methods: Environmental risk was evaluated by assessing the records of National Health Insurance Research Database (NHIRD) and residence-based air pollution (particulate matter with diameter less than 2.5 micrometers (PM_2.5) and PM_2.5-bound polycyclic aromatic hydrocarbons (PAHs)), integrating biomonitoring analysis of environmental pollutants, inflammatory markers and sphingolipid metabolites in case–control populations with mass spectrometry and ELISA. Phenotypic clustering was evaluated by t-distributed stochastic neighbor embedding (t-SNE) integrating 18 clinical and demographic variables.Findings: In the NHIRD dataset, modest increase in the relative risk with time-lag effect for emergency (N=209 837) and outpatient visits (N=638 538) was observed with increasing levels of PM_2.5and PAHs. Biomonitoring analysis revealed a panel of metals and organic pollutants, particularly metal Ni and PAH, posing a significant risk for current asthma (ORs=1.28–3.48) and its severity, correlating with the level of oxidative stress markers, notably Nε-(hexanoyl)-lysine (r=0.108–0.311, p<0.05), but not with the accumulated levels of PM_2.5exposure. Further, levels of circulating sphingosine-1-phosphate and ceramide-1-phosphate were found to discriminate asthma (p<0.001 and p<0.05, respectively), correlating with the levels of PAH (r=0.196, p<0.01) and metal exposure (r=0.202–0.323, p<0.05), respectively, and both correlating with circulating inflammatory markers (r=0.186–0.427, p<0.01). Analysis of six phenotypic clusters and those cases with comorbid type 2 diabetes mellitus (T2DM) revealed cluster-selective environmental risks and biosignatures.Interpretation: These results suggest the potential contribution of environmental factors from multiple sources, their ensuing oxidative stress and sphingolipid remodeling to adult asthma and its phenotypic heterogeneity.