Pirfenidone and nintedanib attenuate pulmonary fibrosis in mice by inhibiting the expression of JAK2.

Background: Pirfenidone and nintedanib were approved by the Food and Drug Administration (FDA) for the treatment of idiopathic pulmonary fibrosis (IPF). These two drugs can slow the progression of the disease, but the specific mechanisms are not fully understood. In the current study, bleomycin (BLM) induced pulmonary fibrosis in mice was accompanied by high p-JAK2 expression in lung tissue, mainly in the nucleus. The expression of p-JAK2 significantly decreased after intragastric administration of pirfenidone and nintedanib. p-JAK2 is reportedly expressed mainly in the cytoplasm and exerts its effect by activating downstream p-STAT3 in the nucleus. Methods: In vivo experiments, pulmonary fibrosis was induced in mice with BLM and then treated with pirfenidone and nintedanib. The levels of transforming growth factor-ß (TGF-ß1), SP-A, SP-D and KL-6 in serum were measured by enzyme-linked immunosorbent assay (ELISA). Pathological staining was performed to assess lung fibrosis in mice, Western blot was performed to detect the expression levels of relevant proteins, and immunofluorescence was performed to observe the fluorescence expression of p-JAK2. In cellular experiments, MLE12 was stimulated with TGF-ß1 and intervened with TGF-ß1 receptor inhibitor and si-JAK2, pirfenidone and nintedanib, respectively, and the related protein expression levels were detected by Western blot. Results: In both in vivo and in vitro experiments, pirfenidone and nintedanib were found to attenuate the expression of lung fibrosis markers by inhibiting the expression of JAK2, which may reduce the entry of p-JAK2 into the nucleus by downregulating JAK2 phosphorylation through inhibition of the TGF-ß receptor. In contrast, inhibition of JAK2 expression greatly reduced the expression of TGF-ß receptor and α-smooth muscles actin (a myofibroblast activation marker). Conclusions: In both in vivo and in vitro experiments, the present study demonstrated that TGF-ß1 promotes JAK2 phosphorylation through a non-classical pathway, and conversely, inhibition of JAK2 expression affects the TGF-ß1 signalling pathway. Therefore, we speculate that TGF-ß1 and JAK2 signaling pathways interact with each other and participate in fibrosis.

Testing the applicability of the Modelling-Ongrowing Fish farms-Monitoring B (MOM-B) investigation system for assessing benthic habitat quality in the manila clam Ruditapes philippinarum aquaculture areas.

The coastal aquaculture areas have been subject to a variety of anthropogenic pressures in recent studies, and reasonable environmental quality assessment is essential for both ecological conservation and production practices. However, there are significant differences between the results produced from various environmental quality assessment regarding the focus of the evaluation and the fundamental methodology. Furthermore, many of these methods are very specific and difficult to adapt to general applications. Here, we utilized the Modelling-Ongrowing fish farms-Monitoring B investigation system (MOM-B), we assessed the benthic habitat quality of benthic bivalve aquaculture areas in the Xiaoqing River estuary located in Laizhou Bay, China. The aim was to validate the accuracy and practicality of this system. The biological, chemical, and sensory parameters of the MOM-B system, temperature, chlorophyll a (Chl-a), food availability, and planktonic larvae were evaluated throughout the investigation area during the summer of 2021. The MOM-B results indicated that the benthic habitat quality in the survey area was good and lightly disturbed, but the quality in the middle tide area began to deteriorate in August, the hottest month of the summer. Environmental factors indicated that the combined effects of high temperatures and fine sedimentation had led to increased environmental stress in the middle tide area. Food availability and population recruitment also suggested that the benthic habitat quality was better in the high tide and low tide areas than in the middle tide area, and more favorable for the survival of Manila clams. The accuracy, sensitivity, and discriminatory ability of the MOM-B system were demonstrated by environmental and biological indicators. This work showed that the MOM-B system is a practical, simple, and sensitive environmental assessment tool that is easy to implement in estuarine and benthic bivalve aquaculture areas. It can be used for long-term continuous monitoring and as an early warning tool for benthic habitat quality.

Swellable microneedle-coupled light-addressable photoelectrochemical sensor for in-situ tracking of multiple pesticides pollution in vivo.

In vivo monitoring of multiple pesticide contamination is of great significance for evaluating the health risks of different pesticides, agricultural production safety, and ecological and environmental assessment. Here, we report a hydrogel microneedle array coupled light-addressable photoelectrochemical sensor for tracking multiple pesticide uptake and elimination in living animals and plants, holding three prominent merits: i) enables in-situ detection of in vivo pesticides, avoiding cumbersome and complex sample transportation and handling processes; ii) allows repeated in vivo sampling of the same organism, improving tracking test controllability and accuracy; iii) avoids lethal sampling, providing a better understanding of the pesticides fate in living organisms. The coupled sensor is mechanically robust for withstanding more than 0.35 N per needle and highly swellable (800 %) for timely extraction of sufficient in vivo solution for analysis. For proof-of-concept, it achieves in-situ detection of atrazine, acetamiprid, and carbendazim efficiently and quantitatively in artificial agarose skin models, mouse skin interstitial fluids, and plant leaves with little inflammatory reaction. This simple, highly integrated, minimally invasive, and high-throughput in vivo monitoring method is ideal for future field environmental monitoring and plant and animal disease diagnosis.

Effectiveness of APG and Honey Gauze in Pressure Injury of Elderly: A Randomized Control Trial.

This study was designed to evaluate the efficiency of the combination of autologous platelet-rich plasma gel (APG) and Manuka honey gauze in the treatment of Stages 3-4 pressure injury of older adults. Patients were divided into four groups: Manuka honey gauze and APG (M + A), Manuka honey gauze (M), APG (A), and a control group (C). Different treatments were given, then wound bed coverage with granulation tissue, wound size reduction, and Pressure Ulcer Scale for Healing (PUSH) score were examined. Paraffin-embedded sections of wound tissues were analyzed and wound swab cultures were assessed. Kruskal-Wallis test and Mann-Whitney U test were performed in statistical analysis at a 5% significance level. A total of 42 patients were accepted. Significant increase of wound bed coverage with granulation tissue (51.24%, P = .004, Kruskal-Wallis test) and decrease of PUSH score (-5) were observed in the M + A group at the end of the observation (P = .032, Mann-Whitney U test). The hematoxylin-eosin staining of wound tissues showed that typical squamous epithelium was seen in wound bed of patient in M + A group. Manuka honey gauze and APG were proved to be superior treatments for pressure injury of old patient. Increase of granulation tissue coverage, reduction of PUSH score, and improved growth of epithelium were observed in M + A group. There was no side-effect, and the treatment would not cause infection.

Morphine timing-dependent modulation of TRPV1 phosphorylation correlates with differential morphine effects on myocardial ischemia/reperfusion injury.

Opioids are used for pain relief in patients suffering from acute myocardial ischemia or infarction. Clinical and laboratory studies demonstrate that morphine treated patients or the experimental animal model suffering acute myocardial ischemia and reperfusion, may worsen myocardial viability. As transient receptor potential vanilloid 1 (TRPV1) plays important roles in pain sensation and cardio-protection, we query whether opioids may exacerbate myocardial viability via interaction with TRPV1 activity in the pain relief. We found the co-expressions of TRPV1 and opioid µ, δ and κ receptors in adult rat cardiomyocytes. Intravenous injection of morphine (0.3 mg/kg) at 20 min after induction of myocardial ischemia, in the rat model of acute myocardial ischemia and reperfusion, induced significant reduction of phosphorylated TRPV1 (p-TRPV1) in the ventricular myocardium and increase in serum cardiac troponin I (cTnI), compared with the ischemia/reperfusion controls (all P < 0.05). The effects of morphine were completely reversed by selective opioid µ, δ and κ receptor antagonists. While significant upregulation of p-TRPV1 (P < 0.05) and improvement of ±dP/dt max (all P < 0.05) were detected in the animals giving the same dose of morphine before induction of myocardial ischemia. The changes in p-TRPV1 correlate with the alterations of cTnI (r = -0.5840, P = 0.0283) and ±dP/dt max (r = 0.8084, P = 0.0005 and r = -0.8133, P = 0.0004, respectively). The findings of this study may indicate that potentiation and attenuation of TRPV1 sensitivity correlate with the improvement of the cardiac performance and the aggravation of myocardial viability, respectively, by giving morphine before and during myocardial ischemia and reperfusion.

Involvement of long non-coding RNA LOXL1-AS1 in the tumourigenesis and development of malignant tumours: a narrative review.

Background and Objective: Long noncoding RNAs (lncRNAs) are involved in a wide variety of physiological and pathological processes in organisms. LncRNAs play a significant role as oncogenic or tumour-suppressing factors in various biological processes associated with malignant tumours and are closely linked to the occurrence and development of malignancies. Lysyl oxidase like 1 antisense RNA 1 (LOXL1-AS1) is a recently discovered lncRNA. It is upregulated in various malignant tumours and is associated with pathological characteristics such as tumour size, tumour node metastasis (TNM) staging, lymph node metastasis, and tumour prognosis. LOXL1-AS1 exerts its oncogenic role by competitively binding with multiple microRNAs (miRs), thereby regulating the expression of downstream target genes and controlling relevant signalling pathways. This article aims to explore the structure and the function of LOXL1-AS1, and the relationship between LOXL1-AS1 and the occurrence and development of human malignant tumours to provide a reference for further clinical research. Methods: English literature on LOXL1-AS1 in the occurrence and development of various malignant tumours was searched in PubMed. The main search terms were "LOXL1-AS1", "tumour". Key Content and Findings: This article mainly summarizes the biological processes in which LOXL1-AS1 is involved in various human malignant tumours and the ways in which this lncRNA affects malignant biological behaviours such as proliferation, metastasis, invasion, and apoptosis of tumour cells through different molecular regulatory mechanisms. This article also explores the potential clinical significance and application prospects of LOXL1-AS1, aiming to provide a theoretical basis and reference for the clinical diagnosis, treatment, and screening of prognostic markers for malignant tumours. Conclusions: LOXL1-AS1 acts as a competing endogenous RNA (ceRNA), binding to miRs to regulate downstream target genes and exert its oncogenic effects. LOXL1-AS1 may become a novel molecular biomarker for cancer diagnosis and treatment in humans, and it may also serve as an independent prognostic indicator.

Stimuli-Responsive Ion Transport Regulation in Nanochannels by Adhesion-Induced Functionalization of Macroscopic Outer Surface.

Responsive regulation of ion transport through nanochannels is crucial in the design of smart nanofluidic devices for sequencing, sensing, and water-energy nexus. Functionalization of the inner wall of the nanochannel enhances interaction with ions and fluid but restricts versatile chemical approaches and accurate characterizations of fluidic interfaces. Herein, we reveal a responsive regulating mechanism of ion transport through nanochannels by polydopamine (PDA)-induced functionalization on the macroscopic outer surface of nanochannels. Responsive molecules were codeposited with PDA on the outer surface of nanochannels and formed a valve of nanometer thickness to manually manipulate ion transport by changing its gap spacing, surface charge, and wettability under external stimulus. The response ratio can be up to 100-fold by maximizing the proportion of responsive molecules on the outer surface. Laminating the codepositions of different responsive molecules with PDA on the channel's outer surface produces multiple responses. A nearly universal adhesion of PDA with responsive molecules on the open outer surface induces nanochannels responsive to different external stimuli with variable response ratios and arbitrary combinations. The results challenge the primary role of functionalization on the nanoconfined interface of nanofluidics and open opportunities for developing new-style nanofluidic devices through the functionalization of macroscopic interface.

A Gender-, Age-, and Weight Status-Specific Analysis of the High Prevalence of Hyperuricemia Among Chinese Children and Adolescents with Obesity.

Objective: To explore the gender-, age-, and weight status-specific prevalence of hyperuricemia (HUA) and its associated risk factors among Chinese children and adolescents with obesity. Methods: A total of 1329 children aged 2-17 years, who were diagnosed with obesity and hospitalized in our center from January 2016 to December 2022 were recruited. They were divided into mild obesity, moderate obesity, and severe obesity groups. HUA was defined as fasting serum uric acid level >420 µmol/L for boys and >360 µmol/L for girls. Multivariate logistic regression analyses were performed to identify risk factors for HUA. Results: The highest proportion of hospitalized obese children was aged 10-13 years comprising 677 (50.9%) followed by those aged 6-9 years comprising 348 (26.2%) whereas the least proportion was aged 2-5 years comprising 76 (5.7%). The above differences in age distribution were still present in subgroup analyses according to weight status. Most hospitalized obese children were boys (64.7%), especially in the severe obesity group (75.0%). The overall estimated prevalence of HUA in obese children was 54.8%. It presented a gradual increase trend over the last 7 years, with more rapidly in boys than in girls. Subgroup analysis by weight status showed that the prevalence of HUA was higher in children with moderate obesity (64.3%) and severe obesity (64.2%) when compared with mild obesity (48.2%) (P all<0.01). Boys reached a relatively high HUA incidence level (≥60%) at age 12, which occurred about 2 years later than in girls (age 10). With 12 years as the cut-off point, a high prevalence of HUA (≥60%) was observed in both genders. Multivariable logistic regression analyses showed that boy (OR=2.844, 95% CI 2.024-3.998), age (OR=1.253, 95% CI 1.155-1.360), BMI-Z score (OR=2.132, 95% CI 1.438-3.162), fasting blood glucose (OR=0.907, 95% CI 0.860-0.956), phosphorus (OR=4.123, 95% CI 2.349-7.239), alkaline phosphatase (OR=1.002, 95% CI 1.001-1.004), creatinine (OR=1.067, 95% CI 1.037-1.098), urea nitrogen (OR=1.193, 95% CI 1.032-1.378), aspartate aminotransferase (OR=1.016, 95% CI 1.002-1.030), triglycerides (OR=1.339, 95% CI 1.075-1.667), and high-density lipoprotein cholesterol (OR=0.381, 95% CI 0.160-0.910) were independently associated with odds of HUA (P all<0.05). Conclusion: The prevalence of HUA in Chinese obese children and adolescents is unexpectedly high. Childhood HUA was significantly associated with obesity. Gender and age differences were observed in the association between childhood obesity and HUA. Obese children aged ≥12 years should be focused on screening the risk of HUA.