Research on the Performance and Modification Mechanism of Gutta-Percha-Modified Asphalt.

Presently, there is a significant focus on the investigation and advancement of polymer-modified asphalt that is both high-performing and environmentally sustainable. This study thoroughly examined the performance and modification mechanism of gutta-percha (GP) as a novel asphalt modifier. The investigation was conducted using a combination of macro- and microscopic testing, as well as molecular dynamics simulations. This work primarily examined the compatibility of GP with asphalt molecular modeling. This paper used molecular dynamics to identify the most suitable mixing temperature. Next, the gray correlation theory was used to discuss the most effective method for preparing gutta-percha-modified asphalt (GPMA). The macro-rheological tests and microscopic performance analysis provided a full understanding of the impact of GP on asphalt properties and the process of alteration. The findings indicate that eucommia ulmoides gum (EUG) exhibits good compatibility with asphalt, while sulfur-vulcanized eucommia ulmoides gum (SEUG) does not demonstrate compatibility with asphalt. Both EUG and SEUG enhance the thermal stability and resistance to deformation of asphalt at high temperatures, with SEUG having a particularly notable effect. However, both additives do not improve the resistance of asphalt to cracking at low temperatures. The manufacturing method for EUG-modified asphalt (EUGMA) involves physical mixing, whereas sulfur-vulcanized eucommia ulmoides gum-modified asphalt (SEUGMA) involves physical mixing together with certain chemical processes. This research establishes a theoretical foundation for the advancement of GP as a novel environmentally friendly and highly effective asphalt modification.

Sequence-dependent effects of hematoporphyrin derivatives (HPD) photodynamic therapy and cisplatin on lung adenocarcinoma cells.

BACKGROUND: Hematoporphyrin derivatives (HPD)-Photodynamic therapy (PDT) in combination with cisplatin (DDP) is an effective anticancer strategy. However, whether the order of combination affects efficacy has not been studied. METHODS: The human lung adenocarcinoma (LUAD) A549 cells were used as the study subjects. After A549 cells were treated with a single medication (PDT/DDP) or a sequential combination (PDT + DDP / DDP + PDT), the cell viability was assayed using the cell counting kit-8 method. Hoechst staining, Annexin-V/propidium iodide (PI) double staining, western blotting, and a real-time quantitative polymerase chain reaction (RT-qPCR) were performed to examine the mechanisms behind the combined effects. RESULTS: A synergistic impact between HPD-PDT and DDP was found. The cell viability in the PDT+DDP group was significantly lower than in the DDP+PDT group. A significant apoptotic profile and a high apoptotic rate were seen in the PDT + DDP group. The western blot showed that the expression levels of Bcl2-associated x(Bax) and cleaved-poly ADP-ribose polymerase (PARP) increased, and those of B-cell lymphoma-2 (Bcl-2) and Caspase-9 decreased in the PDT + DDP group. At the same time, the RT-qPCR revealed the upregulation of Bax and PARP mRNA and the downregulation of Bcl-2 and Caspase-9 mRNA. CONCLUSION: The order of the combination therapy (PDT + DDP / DDP + PDT) was important. The HPD-PDT followed by DDP significantly inhibited LUAD cell viability, which may be related to the mitochondrial apoptotic pathway.

A real-world disproportionality analysis of Everolimus: data mining of the public version of FDA adverse event reporting system.

Background: Everolimus is an inhibitor of the mammalian target of rapamycin and is used to treat various tumors. The presented study aimed to evaluate the Everolimus-associated adverse events (AEs) through data mining of the US Food and Drug Administration Adverse Event Reporting System (FAERS). Methods: The AE records were selected by searching the FDA Adverse Event Reporting System database from the first quarter of 2009 to the first quarter of 2022. Potential adverse event signals were mined using the disproportionality analysis, including reporting odds ratio the proportional reporting ratio the Bayesian confidence propagation neural network and the empirical Bayes geometric mean and MedDRA was used to systematically classify the results. Results: A total of 24,575 AE reports of Everolimus were obtained using data from the FAERS database, and Everolimus-induced AEs occurrence targeted 24 system organ classes after conforming to the four algorithms simultaneously. The common significant SOCs were identified, included benign, malignant and unspecified neoplasms, reproductive system and breast disorders, etc. The significant AEs were then mapped to preferred terms such as stomatitis, pneumonitis and impaired insulin secretion, which have emerged in the study usually reported in patients with Everolimus. Of note, unexpected significant AEs, including biliary ischaemia, angiofibroma, and tuberous sclerosis complex were uncovered in the label. Conclusion: This study provided novel insights into the monitoring, surveillance, and management of adverse drug reaction associated with Everolimus. The outcome of serious adverse events and the corresponding detection signals, as well as the unexpected significant adverse events signals are worthy of attention in order to improving clinical medication safety during treatment of Everolimus.

Effect of photodynamic therapy mediated by hematoporphyrin derivatives on small cell lung cancer H446 cells and bronchial epithelial BEAS-2B cells.

To investigate the effects of photodynamic therapy (PDT) mediated by hematoporphyrin derivatives (HPD) on the proliferation of small cell lung cancer H446 cells and bronchial epithelial BEAS-2B cells. H446 cells and BEAS-2B cells were cultured in vitro with different concentrations of HPD(0, 5, 10, 12, 15, 20 µg/mL) for 4 h, and then irradiated with 630 nm laser with different energy densities (0, 25, 50, 75, 100 mW/cm2). Cell viability of H446 cells and BEAS-2B cells were detected by CCK8 assay. The cell apoptosis was observed with Annexin V-FTTC/PI double staining and Hoechst 33258. The RT-PCR examination was applied to detect the transcriptional changes of the mRNA of Bax、Bcl-2, and Caspase-9. The results of CCK8 showed that when the HPD was 15 µg/mL and the laser power density reached 50 mW/cm2, the cell viability was significantly decreased compared with the black control group. Hoechst 33258 staining showed that with the increase of HPD concentration, the cell density was reduced, and apoptotic cells increased. Flow cytometry assay revealed that the apoptotic rates of the HPD-PDT group of H446 cells and BEAS-2B cells were significantly different from those of the blank control group. The RT-PCR examination showed that the expression levels of Bax and Caspase-9 mRNA in the HPD-PDT group were up-regulated, while the expression levels of Bcl-2 mRNA were down-regulated significantly. HPD-PDT can inhibit H446 cells and BEAS-2B cells growth. The mechanism may be related to up-regulating the expression levels of Bax and Caspase-9 mRNA and down-regulating the expression levels of Bcl-2 mRNA.

Effect of a 630 nm light on vasculogenic mimicry in A549 lung adenocarcinoma cells in vitro.

OBJECTIVE: The objective of this study was to investigate the effect of photodynamic therapy (PDT) on the formation of vasculogenic mimicry (VM) in the human lung adenocarcinoma A549 cell line in vitro. METHODS: The participants were divided into a blank control group, a photosensitizer group, a light group, and a PDT group. Cells from each group were cultured in three dimensions using Matrigel, and vasculogenic mimicry generation was observed microscopically. Periodic Acid-Schiff (PAS) staining was used to verify the vasculogenic mimicry structure. Reverse Transcription-Polymerase Chain Reaction (RT-PCR) was used to detect the expression levels of cellular osteopontin (OPN) and vascular endothelial growth factor (VEGF) mRNA. Western blotting was used to detect the expression levels of cellular OPN and VEGF protein. RESULTS: A549 cells cultured on Matrigel for about six hours revealed VM on PAS staining, and the number of formations was significantly reduced in the PDT group compared with other groups (P < 0.05). The RT-PCR results showed that the PDT group downregulated OPN and VEGF mRNA expression compared with each control group (P < 0.05). Western blot results showed that OPN and VEGF protein expression was downregulated in the PDT group compared with each control group (P < 0.05). The results of RT-PCR showed that the expression of OPN and VEGF mRNA was downregulated in the PDT group compared with each control group (P < 0.05). The results of Western blotting showed that the expression of OPN and VEGF was downregulated in the protein PDT group compared with each control group (P < 0.001). CONCLUSION: Photodynamic therapy significantly inhibited the formation of vasculogenic mimicry in human lung adenocarcinoma A549 cells in vitro and downregulated the expression of OPN, VEGF mRNA, and protein levels.

Oral nifedipine may be a preferential option for treating acute severe hypertension during pregnancy: a meta-analysis.

AIM: To compare oral nifedipine and intravenous labetalol in the treatment of acute severe hypertension in pregnancy (SHP). METHODS: The primary outcomes were the required time to achieve target blood pressure (RTATBP), systolic blood pressure (SBP) and diastolic BP (DBP) after treatment, secondary outcomes were the number of doses (NoD) and adverse events (AEs). RESULTS: There was no difference between oral nifedipine and intravenous labetalol in SBP, DBP, and AE. However, oral nifedipine provided less RTATBP and NoD. CONCLUSION: Oral nifedipine was associated with less RTATBP and NoD and otherwise did not differ from intravenous labetalol.

Cangfudaotan decoction inhibits mitochondria-dependent apoptosis of granulosa cells in rats with polycystic ovarian syndrome.

Polycystic ovary syndrome (PCOS) is a universal endocrine and metabolic disorder prevalent in reproductive aged women. PCOS is often accompanied with insulin resistance (IR) which is an essential pathological factor. Although there is no known cure for PCOS, cangfudaotan (CFDT) decoction is widely used for the treatment of PCOS; nevertheless, the underlying mechanism is not clear. In this study, 40 Sprague-Dawley (SD) rats (female) were randomized to 4 groups, namely the control group, PCOS group, PCOS+CFDT group, and PCOS+metformin group. The rats in the control group were fed a normal-fat diet, intraperitoneally injected with 0.5% carboxymethyl cellulose (CMC, 1 mL/kg/d) for 21 days and orally given saline (1 mL/kg/d) for the next 4 weeks. The rats in the PCOS group, PCOS+CFDT group, and PCOS+Metformin group were fed a high-fat diet (HFD) and intraperitoneally injected with letrozole (1.0 mg/kg) for 21 days. During this period, we recorded the body weight, estrous cycles, and rate of pregnancy in all rats. We also observed the ovarian ultrastructure. Blood glucose indices, serum hormones, and inflammatory factors were also recorded. Then, we detected apoptotic and mitochondrial function, and observed mitochondria in ovarian granular cells by transmission electron microscopy. We also detected genes of ASK1/JNK pathway at mRNA and protein levels. The results showed that CFDT alleviated pathohistological damnification and apoptosis in PCOS rat model. In addition, CFDT improved ovarian function, reduced inflammatory response, inhibited apoptosis of granular cells, and inhibited the operation of ASK1/JNK pathway. These findings demonstrate the occurrence of ovary mitochondrial dysfunction and granular cell apoptosis in PCOS. CFDT can relieve mitochondria-dependent apoptosis by inhibiting the ASK1/JNK pathway in PCOS rats.

Jian-Pi-Yi-Shen decoction inhibits mitochondria-dependent granulosa cell apoptosis in a rat model of POF.

As a widely applied traditional Chinese medicine (TCM), Jian-Pi-Yi-Shen (JPYS) decoction maybe applied in curing premature ovarian failure (POF) besides chronic kidney disease (CKD). In vivo experiments, 40 female SD (8-week-old) rats were randomized into four groups, namely, control group (negative control), POF model group, JPYS treatment group, and triptorelin treatment group (positive control). JPYS group was treated with JPYS decoction (oral, 11 g/kg) for 60 days, and the triptorelin group was treated with triptorelin (injection, 1.5 mg/kg) for 10 days before the administration of cyclophosphamide (CTX) (50 mg/kg body weight) to establish POF model. We examined apoptosis, mitochondrial function, and target gene (ASK1/JNK pathway and mitochondrial fusion/fission) expression. In vitro experiments, the KGN human granulosa cell line was used. Cells were pretreated with CTX (20, 40, and 60 µg/mL) for 24 h, followed by JPYS-containing serum (2, 4, and 8 %) for 24 h. Thereafter, these cells were employed to assess apoptosis, mitochondrial function, and target gene levels of protein and mRNA. In vivo, JPYS alleviated injury and suppressed apoptosis in POF rats. In addition, JPYS improved ovarian function. JPYS inhibit apoptosis of granulosa cells through improving mitochondrial function by activating ASK1/JNK pathway. In vitro, JPYS inhibited KGN cell apoptosis through inhibited ASK1/JNK pathway and improved mitochondrial function. The effects of GS-49977 were similar to those of JPYS. During POF, mitochondrial dysfunction occurs in the ovary and leads to granulosa cell apoptosis. JPYS decoction improves mitochondrial function and alleviates apoptosis through ASK1/JNK pathway.

Retraction Notice to: Overexpression of MicroRNA-340-5p Inhibits Pulmonary Arterial Hypertension Induced by APE by Downregulating IL-1ß and IL-6.

[This retracts the article DOI: 10.1016/j.omtn.2020.05.022.].

Research on the Mechanism of Asperosaponin VI for Treating Recurrent Spontaneous Abortion by Bioinformatics Analysis and Experimental Validation.

Asperosaponin VI (AS6), as the quality marker of Dipsaci Radix, is verified to exert therapeutic effect on alleviating recurrent spontaneous abortion (RSA). However, due to the lack of relevant research, its molecular mechanism is still unclear. We retrieved targets for AS6 and RSA, and then used their overlapped targets for PPI analysis. In addition, we used GO and KEGG enrichment analyses, and molecular docking to investigate the anti-RSA mechanisms of AS6. Furthermore, we conducted in vitro experiments to validate the predictions of network pharmacology. Results showed that a total of 103 AS6-associated targets and 2084 RSA-associated targets, with 49 targets overlapped. GO enrichment analysis showed 845 significant biological processes like decidualization, while KEGG pathway enrichment analysis revealed 76 significant entries including 18 signaling pathways, which were closely linked to PI3K-Akt, HIF-1, TNF, IL-17, and VEGF signaling pathways, etc. Molecular docking findings verified that AS6 had tight link with the key targets including JUN, CASP3, STAT3, SRC, and PTGS2. Notably, in vitro experiments revealed that AS6 treatment could exert lower expressions of JUN, pro-CASP3, CASP3, STAT3, SRC, and PTGS2 in decidual cells compared with progesterone despite the expressions of STAT3, SRC, and PTGS2 with no significant difference, and mifepristone could interfere with the effects. In general, numerous targets and multiple pathways involve during the process of AS6 treatment against RSA. Moreover, our in vitro research first reported that AS6 may regulate the expressions of key targets (JUN, CASP3, STAT3, SRC, and PTGS2) in decidual cells to promote decidualization, thus treating RSA.

Mechanical forces on trophoblast motility and its potential role in spiral artery remodeling during pregnancy.

During the first trimester of pregnancy, cytotrophoblasts (CTBs) differentiate into extravillous trophoblasts (EVTs). EVTs migrate from villus to decidua, invade maternal spiral arteries (SAs) and more strikingly, they migrate against blood flow along the vessels and replace endothelial cells (ECs), completing SA remodeling. Studies have indicated that trophoblast cells are mechanosensitive. They assemble ECs, which can align in the direction of fluid flow. However, how they sense blood flow and transform mechanical stimulations into chemical signals remain largely unexplored. What factors trigger their motility? what are the potential and major factors that guide them to find their path and empower them to migrate against flow? To answer these intricate questions, this review provides some of the novel aspects and sheds new insights into clinical applications.

Salvianolate ameliorates renal tubular injury through the Keap1/Nrf2/ARE pathway in mouse kidney ischemia-reperfusion injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Acute kidney injury (AKI) is a common clinical disease characterized by rapid loss of renal function. Salvianolate is a prescribed Chinese medicine derived from traditional Chinese medicine Salvia miltiorrhiza bunge that possesses many pharmacological effects, the active components extracted from Salvia miltiorrhiza bunge have been proved to protect ischemia-reperfusion (I/R)-AKI. AIM OF THE STUDY: This study aims to validate the therapeutic effect of SAL on I/R-AKI, and explore its potential pharmacological mechanism. MATERIALS AND METHODS: Mice were pretreated with/without salvianolate (10, 30, and 90 mg/kg) before renal ischemia-reperfusion operation. Serum creatinine, BUN, and H&E staining were performed to evaluate renal function. Immunofluorescence analysis was conducted to measure renal tubular injury including inflammatory factors and peroxide level. Apoptosis of the kidney tissues was determined by TUNEL assay. Keap1-Nrf2-ARE and apoptosis signaling pathways were measured by Western blot, RT-PCR, and YO-PRO-1 staining in kidneys or NRK52E cells. RESULTS: Pretreatment with SAL effectively alleviated renal function and ameliorated epithelial tubular injury, oxidative stress, and inflammatory response. Furthermore, the mechanistic study demonstrated that the SAL exerts anti-apoptotic effects through activation of the Keap1-Nrf2-ARE signaling pathway in renal tubular cells. CONCLUSION: These findings indicate the therapeutic benefit of salvianolate in the protection of renal injury from ischemia-reperfusion, and strengthen the evidence for the AKI treatment strategy by the anti-oxidative stress response, suggesting that SAL may be a potential agent for the treatment of AKI.

ZLN005 Alleviates In Vivo and In Vitro Renal Fibrosis via PGC-1α-Mediated Mitochondrial Homeostasis.

Currently, chronic kidney disease (CKD) is one of the most common diseases; it is also a serious threat to human health due to its high mortality, and its treatment is still a major clinical challenge. Mitochondrial dyshomeostasis plays an important role in the development of CKD. ZLN005 is a novel peroxisome-proliferator-activated receptor-γ coactivator-1α (PGC-1α) activator from our laboratory. To explore whether ZLN005 can protect against CKD in vivo and in vitro, a unilateral ureteral obstruction (UUO) model and TGF-ß1-treated renal tubular epithelial cells (TECs), respectively, were used in this study. We found that ZLN005-administrated UUO mice showed less kidney damages than control mice, as indicated by the reduced expression of fibrotic biomarkers in the kidney of UUO mice. ZLN005 treatment also alleviated the TGF-ß1-induced fibrotic phenotype and lipid accumulation in TECs. Our study demonstrated ZLN005 treatment improved mitochondrial homeostasis at least partially via the activation of PGC-1α, thus maintaining mitochondria function and energy homeostasis. In summary, ZLN005 treatment ameliorates UUO-induced renal fibrosis, providing conceptional support for mitochondria-targeting therapies for chronic kidney disease.

Estimation of soil copper content based on fractional-order derivative spectroscopy and spectral characteristic band selection.

Hyperspectral remote sensing is a rapid and nondestructive method to estimate the soil copper content. However, before establishing the spectral estimation model, it is crucial to preprocess the hyperspectral data to eliminate noise and highlight the spectral response characteristics of copper. The two commonly used spectral preprocessing approaches, i.e., the first- and second-order derivatives, may not provide sufficient information on the copper in the soil spectra. Therefore, this study investigates the potential of using the fractional-order derivative (FOD) of the spectra (FOD spectra) for estimating the soil copper content. A total of 170 soil samples were collected, and the soil reflectance spectra were measured outdoors using an ASD FieldSpec3 portable spectrometer. The soil copper content was obtained by chemical analysis in the laboratory. A quantitative estimation model of the soil copper content was established by combining the FOD spectra with different orders and using the partial least squares (PLS) method. The results revealed that the accuracy and prediction ability of the models using different orders of the FOD spectra varied significantly. The model using the 0.8-order FOD spectra performed the best, and the coefficient of determination (R2) and the ratio of the performance to deviation (RPD) of the validation set were 0.6416 and 1.63, respectively. The performance of the model using three characteristic bands (2365.5 nm and 2375.5 nm of the 0.9-order derivatives and 864.5 nm of the 1.1-order derivatives) provided significantly better performance than utilizing all wavelength bands from 400 to 2400 nm. This model provided the optimum predictive ability (R2: 0.6552 vs. 0.6416, RPD: 1.65 vs. 1.63) and was straightforward, requiring only three bands. These results show that it is feasible and practical to establish an accurate and rapid estimation model of the soil copper content using FOD spectra.

Dephosphorylation of AMP-activated protein kinase exacerbates ischemia/reperfusion-induced acute kidney injury via mitochondrial dysfunction.

Kidney tubular epithelial cells are high energy-consuming epithelial cells that depend mainly on fatty acid oxidation for an energy supply. AMP-activated protein kinase (AMPK) is a key regulator of energy production in most cells, but the function of AMPK in tubular epithelial cells in acute kidney disease is unclear. Here, we found a rapid decrease in Thr172-AMPKα phosphorylation after ischemia/reperfusion in both in vivo and in vitro models. Mice with kidney tubular epithelial cell-specific AMPKα deletion exhibited exacerbated kidney impairment and apoptosis of tubular epithelial cells after ischemia/reperfusion. AMPKα deficiency was accompanied by the accumulation of lipid droplets in the kidney tubules and the elevation of ceramides and free fatty acid levels following ischemia/reperfusion injury. Mechanistically, ischemia/reperfusion triggered ceramide production and activated protein phosphatase PP2A, which dephosphorylated Thr172-AMPKα. Decreased AMPK activity repressed serine/threonine kinase ULK1-mediated autophagy and impeded clearance of the dysfunctional mitochondria. Targeting the PP2A-AMPK axis by the allosteric AMPK activator C24 restored fatty acid oxidation and reduced tubular cell apoptosis during ischemia/reperfusion-induced injury, by antagonizing PP2A dephosphorylation and promoting the mitophagy process. Thus, our study reveals that AMPKα plays an important role in protecting against tubular epithelial cell injury in ischemia/reperfusion-induced acute kidney injury. Hence, activation of AMPK could be a potential therapeutic strategy for acute kidney injury treatment.

Rhodomeroterpene alleviates macrophage infiltration and the inflammatory response in renal tissue to improve acute kidney injury.

Inflammation is broadly recognized as an important factor in the pathogenesis of acute kidney injury (AKI), but pharmacological approaches to alleviate inflammation in AKI have not been proved successful in clinical trials. Macrophage infiltration into renal tissue promotes inflammatory responses that contribute to the pathogenesis of AKI. Suppression of renal tissue inflammatory responses is postulated to improve renal injury of patients and animals. Rhodomeroterpene (RMT) is a novel meroterpenoid isolated from the Rhododendron genus that was shown to exert anti-inflammatory action in vivo or in vitro in this study. We investigated the treatment effects of RMT on LPS-induced sepsis and two different AKI models. The results showed that pretreatment with RMT (30 mg kg-1  d-1 , ip, for 3 days) significantly inhibited acute inflammatory responses in LPS-induced septic mice. In both renal ischemia-reperfusion injury (I/R) and sepsis-induced AKI models, RMT (30 mg kg-1  d-1 , ip, for 3 days) ameliorated renal function and injury and alleviated inflammation by reducing the infiltration of immune cells, including macrophages and neutrophils. Furthermore, our study demonstrated that RMT inhibits inflammatory responses in macrophages. The anti-inflammatory effects of RMT may be due to the inactivation of the IKK/NF-κB and PI3K/PDK1/Akt inflammatory signaling pathways in macrophages. Collectively, our findings indicate that RMT ameliorates renal injury and alleviates the renal inflammatory state in different AKI models, suggesting that RMT may be a potential agent for the treatment of AKI.

Monitoring the soil copper pollution degree based on the reflectance spectrum of an arid desert plant.

Visible and near-infrared reflectance spectroscopy offers a rapid, inexpensive, and environmentally friendly method for monitoring copper pollution in the soil. However, the application of this approach in vegetation-covered areas is still a challenge due to interference from plants, making it difficult to acquire soil reflectance spectra. To address this problem, this study assesses whether the reflectance spectrum of a widely distributed arid desert plant (Seriphidium terrae-albae) can be used to rapidly evaluate copper pollution in the soil. A pot experiment was conducted for five months from April to September 2019. The reflectance spectra of the plants were measured in June, July, and August 2019 using an ASD Fieldspec3 spectrometer. Each month, the five vegetation indexes with the highest correlation with the evaluation value of the copper pollution degree were input into an extreme learning machine (ELM) to build a model to monitor the degree of copper pollution in the soil. The results showed that the model could quickly evaluate the degree of copper pollution, but the accuracy varied widely among the calculated vegetation indexes depending on the month when the spectral data were extracted. The model constructed by selecting ten vegetation indexes composed of plant spectra collected in June and July provides high recognition accuracy, reaching 89.02%. Only seven bands were needed due to the model's low complexity, which means that it has great potential to be applied to remote sensing images to establish a real-time monitoring system to detect copper pollution in the soil. This study proposed a simple and rapid method for monitoring copper pollution in soil using plant spectra, and this method could provide extremely valuable for soil protection and management in arid desert areas.