The significance of single-cell transcriptome analysis in epididymis research.

As a crucial component of the male reproductive system, the epididymis plays multiple roles, including sperm storage and secretion of nutritive fluids for sperm development and maturation. The acquisition of fertilization capacity by sperm occurs during their transport through the epididymis. Compared with the testis, little has been realized about the importance of the epididymis. However, with the development of molecular biology and single-cell sequencing technology, the importance of the epididymis for male fertility should be reconsidered. Recent studies have revealed that different regions of the epididymis exhibit distinct functions and cell type compositions, which are likely determined by variations in gene expression patterns. In this research, we primarily focused on elucidating the cellular composition and region-specific gene expression patterns within different segments of the epididymis and provided detailed insights into epididymal function in male fertility.

A Single-Cell Landscape of Spermioteleosis in Mice and Pigs.

(1) Background: Spermatozoa acquired motility and matured in epididymis after production in the testis. However, there is still limited understanding of the specific characteristics of sperm development across different species. In this study, we employed a comprehensive approach to analyze cell compositions in both testicular and epididymal tissues, providing valuable insights into the changes occurring during meiosis and spermiogenesis in mouse and pig models. Additionally, we identified distinct gene expression signatures associated with various spermatogenic cell types. (2) Methods: To investigate the differences in spermatogenesis between mice and pigs, we constructed a single-cell RNA dataset. (3) Results: Our findings revealed notable differences in testicular cell clusters between these two species. Furthermore, distinct gene expression patterns were observed among epithelial cells from different regions of the epididymis. Interestingly, regional gene expression patterns were also identified within principal cell clusters of the mouse epididymis. Moreover, through analysing differentially expressed genes related to the epididymis in both mouse and pig models, we successfully identified potential marker genes associated with sperm development and maturation for each species studied. (4) Conclusions: This research presented a comprehensive single-cell landscape analysis of both testicular and epididymal tissues, shedding light on the intricate processes involved in spermatogenesis and sperm maturation, specifically within mouse and pig models.

Validation and Psychometric Properties of the Chinese Version of the Binge Eating Scale in Young Adults.

Background: Although structured clinical interviews are considered the gold standard for assessing binge eating disorder (BED), the self-administered Binge Eating Scale (BES) has been widely used as a screening tool for BED in clinical research. However, the psychometric properties of the BES among Chinese young adults remain unclear. This study aimed to examine the validity of a Chinese version of the BES with a large sample. Methods: A total of 2182 young adult college students were tested using the Simplified Chinese version of BES (SCBES), the 7-Item Binge-Eating Disorder Screener (BEDS-7), the Zung Self-Rating Depression Scale (SDS), the Generalized Anxiety Disorder Scale (GAD-7), and the Dual-Modes of Self-Control Scale (DMSC). The frequency of objective binge-eating episodes was used as a measure of severity. Validity and reliability of the SCBES were assessed through multiple analyses, along with the item analysis. Results: The data revealed that the SCBES demonstrated reasonable reliability and validity. The Cronbach's α value was 0.813, with a one-month test-retest reliability of 0.835. The exploratory factor analysis (EFA) extracted three first-order factors, which explained a total of 53.82% of the variance. The confirmatory factor analysis (CFA) confirmed the three-factor model (ie, Binge-eating behaviors, Lack of control, Negative affects related to overeating), with a good model fit. The SCBES also demonstrated excellent concurrent and criterion validity, significantly correlating with the BEDS-7 and frequency of objective binge-eating episodes (r=0.760-0.782, p<0.001). Gender, body mass index, depression, anxiety, impulsivity, and self-control were significantly associated with the total score of SCBES. Conclusion: The SCBES demonstrated sound psychometric properties and exhibited good cross-cultural adaptability in Chinese young adults, with a novel three-factor model fitting the data best. This scale could serve as a useful screening tool for identifying the severity of binge eating behaviors among Chinese youths.

In vitro drug screening models derived from different PC12 cell lines for exploring Parkinson's disease based on electrochemical signals of catecholamine neurotransmitters.

Gold nanostructures and a Nafion modified screen-printed carbon electrode (Nafion/AuNS/SPCE) were developed to assess the cell viability of Parkinson's disease (PD) cell models. The electrochemical measurement of cell viability was reflected by catecholamine neurotransmitter (represented by dopamine) secretion capacity, followed by a traditional tetrazolium-based colorimetric assay for confirmation. Due to the  capacity to synthesize, store, and release catecholamines as well as their unlimited homogeneous proliferation, and ease of manipulation, pheochromocytoma (PC12) cells were used for PD cell modeling. Commercial low-differentiated and highly-differentiated PC12 cells, and home-made nerve growth factor (NGF) induced low-differentiated PC12 cells (NGF-differentiated PC12 cells) were included in the modeling. This approach achieved sensitive and rapid determination of cellular modeling and intervention states. Notably, among the three cell lines, NGF-differentiated PC12 cells displayed the enhanced neurotransmitter secretion level accompanied with attenuated growth rate, incremental dendrites in number and length that were highly resemble with neurons. Therefore, it was selected as the PD-tailorable modeling cell line. In short, the electrochemical sensor can be used to sensitively determine the biological function of neuron-like PC12 cells with negligible destruction and to explore the protective and regenerative impact of various substances on nerve cell model.

Microwave-enhanced hydrolysis of cellulose by acidic ionic liquids.

In the [Bmim]Cl reaction medium, five different acidic ionic liquids were used as catalysts to study the effects of reaction time, reaction temperature, system water content, catalyst dosage, microwave power, and other factors on cellulose hydrolysis under microwave irradiation. The results showed that in the [Bmim]Cl reaction system, using N-methylpyrrolidone methylsulfonic acid salt as a catalyst, controlling the microwave reaction time at 10 min, reaction temperature at 130 °C, catalyst dosage at 1 g/g (cellulose), water addition at 0.756 µL/g ([Bmim]Cl), and microwave power at 480 W, resulted in the best cellulose hydrolysis effect with a glucose yield of 74.49%. Compared to conventional heating, the glucose yield increased by 24% and the hydrolysis time was reduced by 77%. Microwave irradiation significantly enhances the cellulose hydrolysis process in an ionic liquid medium.

The potential roles of salivary biomarkers in neurodegenerative diseases.

Current research efforts on neurodegenerative diseases are focused on identifying novel and reliable biomarkers for early diagnosis and insight into disease progression. Salivary analysis is gaining increasing interest as a promising source of biomarkers and matrices for measuring neurodegenerative diseases. Saliva collection offers multiple advantages over the currently detected biofluids as it is easily accessible, non-invasive, and repeatable, allowing early diagnosis and timely treatment of the diseases. Here, we review the existing findings on salivary biomarkers and address the potential value in diagnosing neurodegenerative diseases, such as Alzheimer's disease, Parkinson's disease, Huntington's disease and Amyotrophic lateral sclerosis. Based on the available research, ß-amyloid, tau protein, α-synuclein, DJ-1, Huntington protein in saliva profiles display reliability and validity as the biomarkers of neurodegenerative diseases.

Multiple exposures to low-dose ionizing radiation induced the initiation and progression of pro-atherosclerotic phenotypes in mice and vascular endothelial cell damage.

OBJECTIVE: This study aimed to investigate the effects of low-dose radiation on the abdominal aorta of mice and vascular endothelial cells. METHODS: Wild-type and tumor-bearing mice were exposed to 15 sessions of low-dose irradiation, resulting in cumulative radiation doses of 187.5, 375, and 750 mGy. The effect on the cardiovascular system was assessed. Immunohistochemistry analyzed protein expressions of PAPP-A, CD62, P65, and COX-2 in the abdominal aorta. Microarray technology, Gene Ontology analysis, and pathway enrichment analysis evaluated gene expression changes in endothelial cells exposed to 375 mGy X-ray. Cell viability was assessed using the Cell Counting Kit 8 assay. Immunofluorescence staining measured γ-H2AX levels, and real-time polymerase chain reaction quantified mRNA levels of interleukin-6 (IL-6), ICAM-1, and Cx43. RESULTS: Hematoxylin and eosin staining revealed thickening of the inner membranes and irregular arrangement of smooth muscle cells in the media membrane at 375 and 750 mGy. Inflammation was observed in the inner membranes at 750 mGy, with a clear inflammatory response in the hearts of tumor-bearing mice. Immunohistochemistry indicated increased levels of PAPP-A, P65, and COX-2 post-irradiation. Microarray analysis showed 425 up-regulated and 235 down-regulated genes, associated with processes like endothelial cell-cell adhesion, IL-6, and NF-κB signaling. Cell Counting Kit 8 assay results indicated inhibited viability at 750 mGy in EA.hy926 cells. Immunofluorescence staining demonstrated a dose-dependent increase in γ-H2AX foci. Reverse transcription quantitative PCR results showed increased expression of IL6, ICAM-1, and Cx43 in EA.hy926 cells post 750 mGy X-ray exposure. CONCLUSION: Repeated low-dose ionizing radiation exposures triggered the development of pro-atherosclerotic phenotypes in mice and damage to vascular endothelial cells.

Expression and clinical significance of hypoxia-induced long non-coding RNA TCONS_I2_00001955 in breast cancer.

BACKGROUND: Long non-coding RNAs (lncRNAs) have been found to play important roles in occurrence, development, and metastasis of various tumors. We aimed to screen long non-coding RNAs (lncRNAs) that promote invasion and metastasis of breast cancer cells under hypoxia, and investigate the relationship between lncRNA expression and clinicopathological features and prognosis in invasive breast cancer. METHODS: LncRNA microarray was used to screen the differentially expressed lncRNAs in MCF7, MDA-MB-231, and SKBR3 breast cancer cell lines cultured under normoxia and hypoxia, respectively. Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was used to verify the microarray results. CCK8 and Transwell experiments were performed to identify the lncRNA that promote proliferation, migration, and invasion of breast cancer cells. Expression of the lncRNA and HIF-1α in invasive breast cancer was detected by RNAscope and immunohistochemistry, respectively. Correlation between the lncRNA expression and baseline characteristics was analyzed. Prognostic value of the lncRNA was evaluated using univariate and multivariate Cox regression. RESULTS: Expression of lncRNA TCONS_I2_00001955 in all the three breast cancer cells was increased under hypoxia. Overexpression of TCONS_I2_00001955 significantly enhanced proliferation, migration, and invasion of SKBR3 cells. Positive expression of TCONS_I2_00001955 was associated with recurrence, metastasis, and high expression of HIF-1α (P < 0.05), and it was an independent risk factor for poor disease-free survival of breast cancer. CONCLUSION: Hypoxia-induced lncRNA TCONS_I2_00001955 was associated with aggressive feature and poor prognosis of breast cancer.

Biodosimetry Based on Gamma-H2AX Quantification in Human Peripheral Blood Lymphocytes after Partial-body Irradiation.

ABSTRACT: Quantification of gamma-H2AX foci can estimate exposure to ionizing radiation. Most nuclear and radiation accidents are partial-body irradiation, and the doses estimated using the total-body irradiation dose estimation formula are often lower than the actual dose. To evaluate the dose-response relation of gamma-H2AX foci in human peripheral blood lymphocytes after partial-body irradiation and establish a simple and high throughput model to estimate partial-body irradiation dose, we collected human peripheral blood and irradiated with 0-, 0.5-, 1-, 2-, 3-, 4-, 5-, 6-, and 8-Gy gamma rays to simulate total-body irradiation in vitro. Gamma-H2AX foci were quantitated by flow cytometry at 1 h after irradiation, and a dose-response curve was established for total-body irradiation dose estimation. Then, a partial-body irradiation dose-response calibration curve was established by adding calibration coefficients based on the Dolphin method. To reflect the data distribution of all doses more realistically, the partial-body irradiation dose-response calibration curve was divided into two sections. In addition, partial-body irradiation was simulated in vitro, and the PBI data were substituted into curves to verify the accuracy of the two partial-body irradiation calibration curves. Results showed that the dose estimation variations were all less than 30% except the 25% partial-body irradiation group at 1 Gy, and the partial-body irradiation calibration dose-response curves were YF 1 = - 3.444 x 2 + 18.532 x + 3.109, R 2 = 0.92 (YF ≤ 27.95); YF 2 = - 2.704 x 2 + 37.97 x - 56.45, R 2 = 0.86 (YF > 27.95). Results also suggested that the partial-body irradiation dose-response calibration curve based on the gamma-H2AX foci quantification in human peripheral blood lymphocytes is a simple and high throughput model to assess partial-body irradiation dose.

A Behavioral and Event-Related Potentials Study of Food-Related Inhibitory Control in Probable Binge Eating Disorder.

Background: Similar to addictive disorders, deficits on cognitive control might be involved in the onset and development of Binge Eating Disorder (BED). However, it remains unclear whether general or food-related inhibitory control impairments would be basically linked to overeating and binge eating behaviors. This study thus aimed to investigate behavioral performance and electrophysiological correlates of food-related inhibitory control among individuals with binge eating behavior. Methods: Sixty individuals with probable BED (pBED) and 60 well-matched healthy controls (HCs) were assessed using the typical Stop-Signal Task, a revised Go/No Go Task, and a food-related Go/No Go Task. Besides, another separate sample, including 35 individuals with pBED and 35 HCs, completed the food-related Go/No Go Task when EEG signals were recorded with the event-related potentials (ERPs). Results: The data revealed that the pBED group performed worse with a longer SSRT on the Stop-Signal Task compared with HCs (Cohen's d = 0.58, p = 0.002). Moreover, on the food-related Go/No Go Task, the pBED group had a lower success rate of inhibition in no-go trials (Cohen's d = 0.47, p = 0.012). The ERPs data showed that in comparison with HCs, the pBED group exhibited increased P300 latency (FC1, FC2, F3, F4, FZ) in the no-go trials of the food-related Go/No Go Task (Cohen's d 0.56-0.73, all p < 0.05). Conclusion: These findings suggested that individuals with binge eating could be impaired in both non-specific and food-related inhibitory control aspects, and the impairments in food-related inhibitory control might be linked to P300 abnormalities, implying a behavioral-neurobiological dysfunction mechanism implicated in BED.

Precise Differentiation of Wobble-Type Allele via Ratiometric Design of a Ligase Chain Reaction-Based Electrochemical Biosensor for CYP2C19*2 Genotyping of Clinical Samples.

Due to the comparable stability between the perfect-base pair and the wobble-base pair, a precise differentiation of the wobble-type allele has remained a challenge, often leading to false results. Herein, we proposed a ligase chain reaction (LCR)-based ratiometric electrochemical DNA sensor, namely, R-eLCR, for a precise typing of the wobble-type allele, in which the traditionally recognized "negative" signal of wobble-base pair-mediated amplification was fully utilized as a "positive" one and a ratiometric readout mode was employed to ameliorated the underlying potential external influence and improved its detection accuracy in the typing of the wobble-type allele. The results showed that the ratio between current of methylene blue (IMB) and current of ferrocene (IFc) was partitioned in three regions and three types of wobble-type allele were thus precisely differentiated (AA homozygote: IMB/IFc > 2; GG homozygote: IMB/IFc < 1; GA heterozygote: 1 < IMB/IFc < 2); the proposed R-eLCR successfully discriminated the three types of CYP2C19*2 allele in nine cases of human whole blood samples, which was consistent with those of the sequencing method. These results evidence that the proposed R-eLCR can serve as an accurate and robust alternative for the identification of wobble-type allele, which lays a solid foundation and holds great potential for precision medicine.

A dual-readout sensing platform for the evaluation of cell viability integrating with optical and digital signals based on a closed bipolar electrode.

Cell viability is essential for predicting drug toxicity and assessing drug effects in drug screening. However, the over/underestimation of cell viability measured by traditional tetrazolium colorimetric assays is inevitable in cell-based experiments. Hydrogen peroxide (H2O2) secreted by living cells may provide more comprehensive information about the cell state. Hence, it is significant to develop a simple and rapid approach for evaluating cell viability by measuring the excreted H2O2. In this work, we developed a dual-readout sensing platform based on optical and digital signals by integrating a light emitting diode (LED) and a light dependent resistor (LDR) into a closed split bipolar electrode (BPE), denoted as BP-LED-E-LDR, for evaluating cell viability by measuring the H2O2 secreted from living cells in drug screening. Additionally, the customized three-dimensional (3D) printed components were designed to adjust the distance and angle between the LED and LDR, achieving stable, reliable and highly efficient signal transformation. It only took 2 min to obtain response results. For measuring the exocytosis H2O2 from living cells, we observed a good linear relationship between the visual/digital signal and logarithmic function of MCF-7 cell counts. Furthermore, the fitted half inhibitory concentration curve of MCF-7 to doxorubicin hydrochloride obtained by the BP-LED-E-LDR device revealed a nearly identical tendency with the cell counting kit-8 assay, providing an attainable, reusable, and robust analytical strategy for evaluating cell viability in drug toxicology research.

Catalytic Asymmetric Dehydrogenative Si-H/N-H Coupling: Synthesis of Silicon-Stereogenic Silazanes.

Despite growing progress in the construction of silazanes, the catalytic asymmetric synthesis of silicon-stereogenic silazanes is significantly less explored and remains a considerable challenge. Herein, we report a highly enantioselective synthesis of silicon-stereogenic silazanes via catalytic dehydrogenative coupling of dihydrosilanes with anilines. The reaction readily produces a wide range of chiral silazanes and bis-silazanes in excellent yields and stereoselectivities (up to 99% ee). Further utility of this process is demonstrated by the construction of polycarbosilazanes featuring configurational main chain silicon-stereogenic chirality. In addition, the straightforward transformation of the enantioenriched silazanes delivers various chiral silane compounds in a stereospecific fashion, illustrating their potential utilities as synthons for the synthesis of novel silicon-containing functional molecules.

Periodic traveling waves in the ϕ

We consider the instability and stability of periodic stationary solutions to the classical ϕ^{4} equation numerically. In the superluminal regime, the model possesses dnoidal and cnoidal waves. The former are modulationally unstable and the spectrum forms a figure eight intersecting at the origin of the spectral plane. The latter can be modulationally stable, and the spectrum near the origin in that case is represented by vertical bands along the purely imaginary axis. The instability of the cnoidal states in that case stems from elliptical bands of complex eigenvalues far from the spectral plane origin. In the subluminal regime, there exist only snoidal waves which are modulationally unstable. Considering the subharmonic perturbations, we show that the snoidal waves in the subluminal regime are spectrally unstable with respect to all subharmonic perturbations, while for the dnoidal and cnoidal waves in the superluminal regime, the transition between the spectrally stable state and the spectrally unstable state occurs through a Hamiltonian Hopf bifurcation. The dynamical evolution of the unstable states is also considered, leading to some interesting localization events on the spatio-temporal backgrounds.

Single-cell transcriptomes reveal heterogeneity of chlorine-induced mice acute lung injury and the inhibitory effect of pentoxifylline on ferroptosis.

To investigate the effect of pentoxifylline (PTX) on Chlorine (Cl2)-induced acute lung injury (ALI) by single-cell RNA sequencing (scRNA-seq). Female BALB/c mice were exposed to Cl2 at 400 ppm for 15 min. H&E staining was used to observe the degree of lung injury. scRNA-seq was conducted to analysis of normal and Cl2-exposed mice lung tissues. Immunofluorescence was used to observe genes of interest. Thirty-two mice were randomly divided into four groups: Control, Cl2, Cl2+Fer-1, Cl2+PTX. TEM, WB and ELISA were used to detect ferroptosis-related indicators. The 5, 8, 10, 12, 16, 20 clusters were epithelial cells and 4, 15, 18, 19, 21 clusters were endothelial cells. Pseudo-time analysis revealed the differentiation trajectory of epithelial cells and key regulatory genes (Gclc, Bpifa1, Dnah5 and Dnah9) during the process of injury. Cell-cell communication analysis identified several important receptor-ligand complexes (Nrp1-Vegfa, Nrp2-Vegfa, Flt1-Vegfa and Flt4-Vegfa). Ferroptosis were found up-regulated in epithelial and endothelial cells by GSVA analysis. Highly expressed genes to which closely related ferroptosis were found by SCENIC analysis. PTX could significantly decrease the levels of MDA and abnormal high expression of solute carrier family 7 member 11 (SLC7A11, the key transporter of cystine) as well as increase the expression of GSH/GSSG and glutathione peroxidase 4 (GPX4) (p < 0.05). This study revealed novel molecular features of Cl2-induced ALI. PTX may be a potential specific drug by inhibiting the process of ferroptosis in epithelial and endothelial cells.

Melatonin inhibits senescence-associated melanin pigmentation through the p53-TYR pathway in human primary melanocytes and the skin of C57BL/6 J mice after UVB irradiation.

UVB exposure accelerates skin aging and pigmentation. Melatonin effectively regulates tyrosinase (TYR) activity and aging. The purpose of this study was to determine the association between premature senescence and pigmentation, and the mechanism of melanin synthesis effected by melatonin. Primary melanocytes were extracted and identified from the male foreskin. To inhibit TYR expression, primary melanocytes were transduced with the lentivirus pLKD-CMV-EGFP-2A-Puro-U6-TYR. The wild-type TYR(+/+) and TYR(-/-) or TYR(+/-) knockout C57BL/6 J mice were used to determine the role of TYR on melanin synthesis in vivo. Results showed that UVB-induced melanin synthesis is dependent on TYR in primary melanocytes and mice. Furthermore, in primary melanocytes pretreated with Nutlin-3 or PFT-α to up or downregulate p53, results showed that premature senescence and melanin synthesis increased in primary melanocytes after UVB irradiation at 80 mJ/cm2, and further increased after being treated with Nutlin-3, while significantly decreased with PFT-α. In addition, melatonin inhibited UVB-induced premature senescence associated with inactivation of p53 and phosphorylation of p53 on Ser15 (ser-15), a decrease of melanin synthesis accompanied by reduced TYR expression. Moreover, skin erythema and pigmentation induced by UVB were reduced in the dorsal and ear skin of mice topically pretreated with 2.5% melatonin. These indicate that melatonin inhibits UVB-induced senescence-associated pigmentation via the p53-TYR pathway in primary melanocytes and prevents pigmentation obviously in the dorsal and ear skin of C57BL/6 J mice after UVB irradiation. KEY MESSAGES: P53 links UVB irradiation-induced senescence and senescence-associated pigmentation and regulates TYR in primary melanocytes after UVB irradiation. Melatonin inhibits senescence-associated pigmentation through the p53-TYR pathway in primary melanocytes. Melatonin prevents skin erythema and melanin pigmentation induced by UVB irradiation in the dorsal and ear skin of C57BL/6J mice.

Telomerase reverse transcriptase and neurodegenerative diseases.

Neurodegenerative diseases (NDs) are chronic conditions that result in progressive damage to the nervous system, including Alzheimer's disease (AD), Parkinson's disease (PD), Huntington's disease (HD), and Amyotrophic lateral sclerosis (ALS). Age is a major risk factor for NDs. Telomere shortening is a biological marker of cellular aging, and telomerase reverse transcriptase (TERT) has been shown to slow down this process by maintaining telomere length. The blood-brain barrier (BBB) makes the brain a unique immune organ, and while the number of T cells present in the central nervous system is limited, they play an important role in NDs. Research suggests that NDs can be influenced by modulating peripheral T cell immune responses, and that TERT may play a significant role in T cell senescence and NDs. This review focuses on the current state of research on TERT in NDs and explores the potential connections between TERT, T cells, and NDs. Further studies on aging and telomeres may provide valuable insights for developing therapeutic strategies for age-related diseases.

Protective effects of pentoxifylline against chlorine-induced acute lung injury in rats.

OBJECTIVE: Chlorine is a chemical threat agent that can be harmful to humans. Inhalation of high levels of chlorine can lead to acute lung injury (ALI). Currently, there is no satisfactory treatment, and effective antidote is urgently needed. Pentoxifylline (PTX), a methylxanthine derivative and nonspecific phosphodiesterase inhibitor, is widely used for the treatment of vascular disorders. The present study was aimed to investigate the inhibitory effects of PTX on chlorine-induced ALI in rats. METHODS: Adult male Sprague-Dawley rats were exposed to 400 ppm Cl2 for 5 min. The histopathological examination was carried out and intracellular reactive oxygen species (ROS) levels were measured by the confocal laser scanning system. Subsequently, to evaluate the effect of PTX, a dose of 100 mg/kg was administered. The activities of superoxide dismutase (SOD) and the contents of malondialdehyde (MDA), glutathione (GSH), oxidized glutathione (GSSG) and lactate dehydrogenase (LDH) were determined by using commercial kits according to the manufacturer's instructions. Western blot assay was used to detect the protein expressions of SOD1, SOD2, catalase (CAT), hypoxia-inducible factor (HIF)-1α, vascular endothelial growth factor (VEGF), occludin, E-cadherin, bcl-xl, LC 3, Beclin 1, PTEN-induced putative kinase 1 (PINK 1) and Parkin. RESULTS: The histopathological examination demonstrated that chlorine could destroy the lung structure with hemorrhage, alveolar collapse, and inflammatory infiltration. ROS accumulation was significantly higher in the lungs of rats suffering from inhaling chlorine (P<0.05). PTX markedly reduced concentrations of MAD and GSSG, while increased GSH (P<0.05). The protein expression levels of SOD1 and CAT also decreased (P<0.05). Furthermore, the activity of LDH in rats treated with PTX was significantly decreased compared to those of non-treated group (P<0.05). Additionally, the results also showed that PTX exerted an inhibition effect on protein expressions of HIF-1α, VEGF and occludin, and increased the level of E-cadherin (P<0.05). While the up-regulation of Beclin 1, LC 3II/I, Bcl-xl, and Parkin both in the lung tissues and mitochondria, were found in PTX treated rats (P<0.05). The other protein levels were decreased when treated with PTX (P<0.05). CONCLUSION: PTX could ameliorate chlorine-induced lung injury via inhibition effects on oxidative stress, hypoxia and autophagy, thus suggesting that PTX could serve as a potential therapeutic approach for ALI.

Pentoxifylline inhibits phosgene-induced lung injury via improving hypoxia.

Inhalation of high concentrations of phosgene often causes pulmonary edema, which obstructs the airway and causes tissue hypoxia. There is currently no specific antidote. This study was performed to investigate the effect behind pentoxifylline (PTX) treatment for phosgene-induced lung injury in rat models. Rats were exposed to phosgene. The protein levels of hypoxia-inducible factor-1α (HIF-1α), vascular endothelial growth factor (VEGF), and occludin proteins in lung tissue were determined. The effect of both prophylactic and therapeutic administration of PTX (50 mg/kg and 100 mg/kg) was evaluated. The lung permeability index and HIF-1α protein level increased, the arterial blood oxygenation index (PaO2/FIO2 ratio) and occludin protein level decreased significantly 6 h after phosgene exposure (P < 0.05). PTX exerted protective effects by HIF-1α-VEGF-occludin signaling pathway to some extent. Moreover, prophylactic, but not therapeutic administration of PTX (100 mg/kg), exhibited a significant protective effect. Pretreatment with PTX protected against phosgene-induced lung injury, possibly by inhibiting differential expression of HIF-1α, VEGF, and occludin.

Cell viability and drug evaluation biosensing system based on disposable AuNPs/MWCNT nanocomposite modified screen-printed electrode for exocytosis dopamine detection.

Cell viability, as an important index to evaluate drug effects, usually was measured by tetrazolium colorimetric assay, playing a key role in drug development and drug screening. Tedious operating procedures, unsatisfactory sensitivity and abominable environments perplex researchers to acquire more detailed in vivo-relevant biological information. Herein, a simple and low-cost cell viability and drug evaluation biosensing system-based on multiwalled carbon nanotubes, gold nanoparticles and Nafion modified screen-printed electrode (SPE) biosensor was constructed for detection of dopamine (DA) released from living cells to evaluate cytotoxicity of antineoplastic drugs such as cisplatin and resveratrol. The biosensing system was demonstrated to display exceptional selectivity, excellent flexibility and good stability toward DA measurement in complex bio-samples. Additionally, the satisfactory recoveries of DA in real samples revealed the reliability and accuracy of the biosensing system in practical application. The IC50 curves respectively obtained by the biosensing system and tetrazolium colorimetric assay provided similar IC50 value but distinctly different dose-effect relationship, which confirmed the enormous potential of the biosensor in cell viability and described drug efficacy profiles in cell function. In short, the cell viability and drug evaluation system using SPE biosensor paves a new way in drug screening and pharmaceutical application to measure bioactive molecule such as DA.