Idiopathic pulmonary fibrosis (IPF) is a chronic interstitial lung disease of unknown origin that usually results in death from secondary respiratory failure within 2–5 years of diagnosis. Recent ...studies have identified key roles of cytokine and growth factor pathways in the pathogenesis of IPF. Although there have been numerous clinical trials of drugs investigating their efficacy in the treatment of IPF, only Pirfenidone and Nintedanib have been approved by the FDA. However, they have some major limitations, such as insufficient efficacy, undesired side effects and poor pharmacokinetic properties. To give more insights into the discovery of potential targets for the treatment of IPF, this review provides an overview of cytokines, growth factors and their signaling pathways in IPF, which have important implications for fully exploiting the therapeutic potential of targeting cytokine and growth factor pathways. Advances in the field of cytokine and growth factor pathways will help slow disease progression, prolong life, and improve the quality of life for IPF patients in the future.
Purpose
Triple-negative breast cancer (TNBC) is the most malignant subtype of breast cancer. As yet, chemotherapy with drugs such as doxorubicin is the main treatment strategy. However, drug ...resistance and dose-dependent toxicities restrict their clinical use. Natural products are major sources of anti-tumor drugs. OSW-1 is a natural compound with strong anti-cancer effects in several types of cancer, but its effects on the efficacy of chemotherapy in TNBC and its underlying mechanism remain unclear.
Methods
The inhibitory activities of OSW-1 and its combination with several chemotherapy drugs were tested using
in vitro
assays and
in
vivo
subcutaneous and metastatic mouse TNBC models. The effects of the mono- and combination treatments on TNBC cell viability, apoptosis, autophagy and related signaling pathways were assessed using MTT, flow cytometry, RNA sequencing and immunology-based assays. In addition, the
in vivo
inhibitory effects of OSW-1 and (combined) chemotherapies were evaluated in subcutaneous and metastatic mouse tumor models.
Results
We found that OSW-1 induces Ca
2+
-dependent mitochondria-dependent intrinsic apoptosis and cyto-protective autophagy through the PI3K-Akt-mTOR pathway in TNBC cells
in vitro
. We also found that OSW-1 and doxorubicin exhibited strong synergistic anti-TNBC capabilities both
in vivo
and
in vitro
. Combination treatment strongly inhibited spontaneous and experimental lung metastases in 4T1 mouse models. In addition, the combination strategy of OSW-1 + Carboplatin + Docetaxel showed an excellent anti-metastatic effect
in vivo
.
Conclusions
Our data revealed the mode of action and molecular mechanism underlying the effect of OSW-1 against TNBC, and provided a useful guidance for improving the sensitivity of TNBC cells to conventional chemotherapeutic drugs, which warrants further investigation.
Recently, the applications of cold atmospheric plasma (CAP) in liquid treatment have attracted increasing attention owing to its excellent medical efficacy. It has been proved that CAP can ...effectively enhance the biological activity of vegetable oils due to the generation of reactive species. Optimising the reactor parameter is an important approach to regulate reactive species in plasma‐activated oil to obtain better biological effects. In this study, a self‐made jet array driven by a pulsed power supply was used to generate large‐area plasma to irradiate perilla seed oil (PSO), with the formation of plasma‐activated perilla seed oil (PAPSO). By means of laser‐induced fluorescence and chemical titration, the relative density of hydroxyl radical radical in plasma jet, as well as the activity of PAPSO were measured under different discharge parameters, and realised the control of the activity of PAPSO. In vitro experiments showed that PAPSO significantly enhanced its ability to inhibit cancer cells proliferation and induce apoptosis after plasma treatment, which provides a reference for cancer treatment. This study is helpful to further understand the influence of plasma dose effect on the activity of media and provide guidance for related plasma medical applications.
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•Non-thermal plasma inactivates Aspergillus flavus spores with the Weibull + Tail model.•Non-thermal plasma induces cell apoptosis by the caspase-dependent mitochondrial ...pathway.•Non-thermal plasma inhibits aflatoxin B1 production by modulating the expression of biosynthetic genes.•Non-thermal plasma can effectively degrade aflatoxin B1 in two pathways.
Aspergillus flavus (A. flavus) and its toxic metabolites, aflatoxins, are widely distributed in agricultural products and foods, posing a grave threat to food safety and public health. This study investigated the decontamination effects and mechanism of non-thermal plasma (NTP) on A. flavus and aflatoxins. NTP primarily generated reactive oxygen and nitrogen species (RONS), effectively inactivating A. flavus spores via the Weibull + Tail model. The results of ultrastructural observation and membrane integrity revealed that fungal inactivation by NTP was mainly attributed to intracellular destruction rather than the direct damage of cell membranes. Furthermore, NTP induced the accumulation of intracellular ROS and NO, disrupting anti-oxidative and energy metabolic systems, thereby inducing fungal apoptosis via a caspase-dependent mitochondrial pathway, which is responsible for A. flavus spore inactivation. In addition, the results showed that NTP reduced aflatoxin B1 (AFB1) production by regulating the expression of key genes in the aflatoxin biosynthetic pathway. Moreover, NTP effectively degraded AFB1 by disintegrating the furan ring, modifying the methoxy group, and forming the double bond in cyclopentanone, thereby decreasing the toxicity of AFB1. Hence, NTP exhibits exceptional decontamination effects against A. flavus and AFB1 via fungal inactivation, aflatoxin biosynthesis suppression, and AFB1 degradation, making it a viable alternative strategy for agricultural disinfection.
Aflatoxins pose a threat to humans and animals and are not easily degraded. Cold atmospheric plasma (CAP) can effectively decontaminate aflatoxins in foods. In this study, a Reactive Molecular ...Dynamics (RMD) simulation was carried out to examine the interactions of reactive oxygen species (ROS) produced in CAP and aflatoxin B1 (AFB1). The simulation results indicated that ROS (O atoms, OH radicals, and H2O2 molecules considered in present study) can reduce the toxicity of AFB1 by the addition reaction of the double C8C9 bond, the ring-opening reaction of the terminal furan ring, and the destruction of the lactone ring. The ketone carbonyl reduction and double CC bonds formation of cyclopentenone can also be observed in the simulation. The reaction pathways and the final products unveiled by simulation results agree well with the experimental observations, which clearly indicate that CAP can degrade AFB1 by destroying the key structures of AFB1 in a non-thermal way, and further suggest the optimized way to degrade aflatoxins in applications.
Reactive Molecular Dynamics simulations were applied to visualize the chemical damaging mechanism of AFB1 upon the impact of reactive oxygen species during food processing by cold atmospheric plasma (CAP). Such detailed information about the pathways of specific ROS is difficult to obtain experimentally. These results can be used to understand the structural changes at the atomic level that could provide theoretical instruction to industrialists. This work can also contribute to the optimization of process parameters to drive the improvement of operating conditions and the development of CAP sources in the food industry.
This study was designed to develop a cold plasma +222 nm ultraviolet (CP + UV) sterilization device in the food industry. Response surface methodology was applied to evaluate the effects of three ...treatment conditions on the antibacterial activity of CP + UV. The optimum treatment conditions (plasma gas flow: 4 m3/min, irradiation distance: 4 cm, treatment time: 60 s) were selected to optimize the reactor parameters of CP and 222 nm UV sterilization equipment, and its effects against the growth of S. aureus on different food contact materials were investigated. Results showed that the antibacterial activity against S. aureus was strongest when the plasma was operated at 8.5 kHz, 2.5 W/cm2 with two net layers of electrodes arranged transversely at a distance of 5 cm between the plasma outlet plane and UV centerline plane. After 60 s of CP + UV treatment, the number of S. aureus on the glass sheet, polypropylene film, corrugated paper, and kraft paper decreased by 4.5, 4.1, 1.5, and 2.4, respectively (p < 0.05). In summary, a novel CP + UV device was developed, which can be used for sterilization on different food surfaces, which potentially contributes to the development of the food industries.
•Combination of CP and UV treatment was used for sterilization.•Staphylococcus aureus on the glass sheet decreased by 5.40 Log CFU/cm2 after 60s treatment.•The order of sterilization was glass sheet > OPP film > kraft paper > corrugated paper.•A novel CP + UV device was developed to sterilize different food surfaces.
Brain metastasis is the main cause of treatment failure and melanoma-related death. Inadequate concentrations of therapeutic drugs in the brain due to the blood-brain barrier (BBB) pose a major ...challenge in the treatment of brain metastasis. Antipsychotics can cross the BBB to reach the brain. Fluphenazine (FPZ) inhibits the survival of melanoma cells in vitro. However, its efficacy in suppressing the metastasis of melanoma, especially brain metastasis, remains unknown. Therefore, we explored whether fluphenazine (FPZ) can be repurposed for treating melanoma metastasis. A subcutaneous tumor model, and experimental metastasis models that simulate the outgrowth of melanoma cells in the brain, lung, and bone were established to verify the inhibitory effect of FPZ on melanoma cells. FPZ showed potential inhibitory effects against melanoma both in vivo and in vitro. It induced G0/G1 phase arrest and-mitochondrion-mediated intrinsic apoptosis, and inhibited autophagic flux in melanoma cells in vitro. In vivo, subcutaneous tumor, brain, lung, and bone models of metastatic melanoma were established. Intraperitoneal injection of FPZ (8 mg/kg) significantly inhibited melanoma growth in the subcutaneous and experimental metastasis models. In a lung metastasis model, FPZ reduced the proportion of M2 macrophages and increased the proportion of CD8
+
T cells and NK cells in vivo, thereby promoting an anticancer immune response. The findings of this study indicate that FPZ is a potential drug candidate for treating metastatic melanoma.
The food industry is plagued by mycotoxin contamination, and obtaining mycotoxin-free products has become a great challenge. With the advancement of cold atmospheric plasma (CAP) technology, new ...ideas for mycotoxin decontamination have emerged. The reactive species in plasma can act on the toxic structural groups through various reaction pathways, which are not yet completely clear. In this paper, we investigated the reaction mechanisms of six mycotoxins upon the impact of reactive oxygen species (ROS) employing reactive molecular dynamics (RMD) simulation. The degradation pathways of mycotoxins were revealed, and the reaction types of main toxic groups were summarized, including addition, oxidation, reduction, ring opening, side chain shedding, and even skeleton structure breaking. The degradation patterns of the double C=C bond and lactone ring were analyzed in detail. Besides the addition reaction, the double C=C bond can also be reduced by bond breaking or hydrogen atom abstraction reaction. The degradation processes of the lactone ring mainly include ring-opening reaction and reduction of lactone carbonyl group. The reaction processes can contribute to an improved understanding of the mechanisms of mycotoxins degradation by plasma and are also valuable for the degradation of other organic pollutants with the same structural groups.
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•The degradation mechanisms of major mycotoxins induced by plasma ROS are revealed.•The degradation patterns of toxic structural groups are comprehensively analyzed.•The double C=C bond mainly undergoes the addition reaction or is reduced.•The lactone ring mainly undergoes ring opening and reduction of the carbonyl group.•Other common reactions include oxidation, side chain shedding, skeleton breaking.
Objective： To evaluate the feasibility of DNA image cytometry （DNA-ICM） as a primary screening method for esophageal squamous cell cancer （ESCC）. Methods： A total of 5,382 local residents aged 40-69 ...years from three high-risk areas in China （Linzhou in Henan province, Feicheng in Shandong province and Cixian in Hebei province） from 2008 to 2011 were recruited in this population-based screening study. And 2,526 subjects declined to receive endoscopic biopsy examination with Lugol＇s iodine staining, while 9 and 815 subjects were excluded from liquid-based cytology and DNA-ICM test respectively due to slide quality. Finally, 2,856, 5,373 and 4,567 subjects were enrolled in the analysis for endoscopic biopsy examination, liquid-based cytology and DNA-ICM test, respectively. Sensitivity （SE）, specificity （SP）, negative predictive values （NPV） and positive predictive values （PPV） as well as their 95% confidence intervals （95% CI） for DNA-ICM, liquid-based cytology and the combination of the two methods were calculated. Receiver operating characteristic （ROC） curves were applied to determine the cutoff point of DNA-ICM for esophageal cancer. Results： DNA-ICM results were significantly correlative with esophageal cancer and precancer lesions （X2= 18.016, P〈0.001）. The cutoff points were 5,802, 5,803 and 8,002 based on dissimilar pathological types of low grade intraepithelial neoplasia （LGIN）, high grade intraepithelial neoplasia （HGIN）, and ESCC, respectively, and 5,803 was chosen in this study considering the SE and SP. The SE, SP, PPV, NPV of DNA-ICM test （cutoff point 5,803） combined with liquid-based cytology threshold atypical squamous cells of undetermined significance （ASCUS） were separately 72.1% （95% CI： 70.3%-73.9%）, 43.3% （95% CI. 41.3%-45.3%）, 22.8% （95% CI： 21.1%-24.5%） and 87.0% （95% CI： 85.7%-88.3%） for LGIN, 85.7% （95% CI： 84.3%-87.1%）, 41.3% （95% CI： 39.3%-43.3%）, 4.6% （95% CI： 3.8%-5.4%） and 98.9% （95% CI： 98.5%-99.3%） for HGIN, and 96.0% （95% CI： 95.2%-96.8%）, 40.8% （95% CI： 38.8%-42.8%）, 1.7% （95% CI： 1.2%-2.2%） and 99.9% （95% CI： 99.8%-100.0%） for ESCC. Conclusions： It is possible to use DNA-ICM test as a primary screening method before endoscopic screening for esophageal cancer.
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